WO1996033208A1 - Antibody purification by low-ph hydrophobic interaction chromatoggraphy - Google Patents
Antibody purification by low-ph hydrophobic interaction chromatoggraphy Download PDFInfo
- Publication number
- WO1996033208A1 WO1996033208A1 PCT/US1996/004683 US9604683W WO9633208A1 WO 1996033208 A1 WO1996033208 A1 WO 1996033208A1 US 9604683 W US9604683 W US 9604683W WO 9633208 A1 WO9633208 A1 WO 9633208A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- antibody
- antibodies
- fragments
- column
- buffer
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/32—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products of oncogenes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/14—Extraction; Separation; Purification
- C07K1/16—Extraction; Separation; Purification by chromatography
- C07K1/20—Partition-, reverse-phase or hydrophobic interaction chromatography
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/06—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies from serum
- C07K16/065—Purification, fragmentation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2839—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the integrin superfamily
- C07K16/2845—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the integrin superfamily against integrin beta2-subunit-containing molecules, e.g. CD11, CD18
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/54—F(ab')2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/55—Fab or Fab'
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
- C07K2317/622—Single chain antibody (scFv)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S435/00—Chemistry: molecular biology and microbiology
- Y10S435/803—Physical recovery methods, e.g. chromatography, grinding
Definitions
- This invention relates generally to antibody purification.
- the invention relates to a method for recovering an antibody fragment from variants, impurities, and contaminants associated therewith.
- Hydrophobic interaction chromatography is a useful tool for separating molecules based on their hydrophobicity.
- sample molecules in a high salt buffer are loaded on the HIC column.
- the salt in the buffer interacts with water molecules to reduce the solvation of the molecules in solution, thereby exposing hydrophobic regions in the sample molecules which are consequently adsorbed by the HIC column.
- HIC has been used by various researchers for purification of antibodies. Danielsson et al., Journal of Immunological Methods 115:79-88 (1988) found that HIC was particularly useful for purification of monoclonal antibodies from mouse ascites when the isoelectric point of the antibodies was below 7.2. HIC was performed with an Alkyl Superose HR column. The buffer system was 0.1 M phosphate, with addition of ammonium sulfate. Usually the starting buffer contained 2M ammonium sulfate. Bridonneau et al, Journal of Chromatography 616:197-204 (1993) were interested in determining whether or not different HIC columns could be used for selective purification of human immunoglobulin G (IgG) subclasses.
- IgG immunoglobulin G
- the antibodies were adsorbed on Phenyl-, Butyl-, or Octyl-SepharoseTM columns in 1 M ammonium sulfate (pH 7.0) and eluted with decreasing salt gradient.
- Octyl-Sepharose M medium yielded a poorly adsorbed fraction somewhat enriched in IgG 2a . See also Berkowitz et al, Journal of Chromatography 389:317-321 (1 87); Gagnon et al (90th Annual Meeting, American Society for Microbiology, Anaheim, May 13-17, 1990) Abstract No. 0-4; Johansson et al. Biol. Recombinant Microorg. Ani . Cells.
- HIC has also been used for purifying antibody fragments. Inouye et al., Protein Engineering, pgs 6, 8 and 1018-1019 (1993); Inouye et al., Animal Cell Technology: Basic & Applied Aspects 5:609-616 (1993); Inouye et al, Journal of Biochemical and Biophysical Methods 26:27-39 (1993) and Morimoto et al. , Journal of Biochemical and Biophysical Methods 24: 107- 117 ( 1992) prepared F(ab') 2 fragments from pepsin digests of mouse IgM monoclonal antibodies using a TSKgel Ether-5PW ' M HIC column.
- the antibody fragments were salted out with 60% ammonium sulfate and the precipitates were dissolved into phosphate-buffered saline (PBS, pH7.4) containing 1 M ammonium sulfate. This solution was loaded onto the HIC column which had been equilibrated with PBS also containing 1M ammonium sulfate.
- PBS phosphate-buffered saline
- StlKTluJTE SHEET (RtHE 26) adsorbed onto the column were eluted by reducing the ammonium sulfate concentration in the elution buffer to 0M
- Inouye et al found that the fraction containing the F(ab')-*, was homogeneous by both SDS-PAGE and gel filtration HPLC The method was considered to be suitable for large-scale purification of F(ab')2 fragments Similarly, Rea et al , Journal of Cell. Biochem. Suppl 0, Abstract No.
- X 1 -206 ( 17 Part A), p.50 (1993) evaluated HIC for purification of a F(ab') 7 fragment produced by peptic digestion of a mu ⁇ ne lgG2 a monoclonal antibody. Protein A purification for removal of residual intact antibody preceded the HIC step The purification performance of three different HIC columns was tested at several different salts and pHs. POROS PE (Phenyl ether) was found to be the best column and phosphate-buffered sodium sulfate at pH
- the instant invention relates to low pH interaction chromatography (LPHIC) for antibody purification
- LPHIC low salt concentrations
- the LPHIC is performed at low salt concentrations, i , about 0-0.25M salt, preferably about 0-0.1 M salt and more preferably 0-50mM salt
- This low salt concentration also applies to the loading buffer
- no salt gradient is used to elute the antibody
- the mvention provides a process for purifying an antibody from a contaminant which comprises loading a mixture containing the antibody and the contaminant on a hydrophobic interaction chromatography column and elutmg the antibody from the column with a buffer having a pH of about 2.5-4.5.
- the buffer is at a pH of about 2.8-3.5 and more preferably at a pH of about 3 1
- the mixture loaded onto the column is at about the same pH as the elution buffer.
- the method is particularly useful for purifying antibody fragments, especially correctly folded and disulfide linked antibody fragments (e g Fab fragments) from contaminating antibody fragments which are not correctly folded and/or disulfide linked
- the mvention resides, at least in part, in the identification of a problem associated with the formation of recombinant tmmunoglobulins It has been observed that such production results in the formation of functional F(ab')- > antibodies as well as a variety of incorrectly associated light and heavy fragments. The most difficult impurity to remove has been characterized herein as a correctly folded antibody fragment whose light and heavy chains fail to associate through disulfide bonding.
- This antibody can be detected by SDS PAGE gels and Reverse Phase HPLC as heavy and light chains.
- the LPHIC descnbed herein provides a means for substantially removing this contaminant from partially purified compositions derived from host cells producing the recombinant antibody fragment, although it is not limited to purification of recombinant products.
- the invention also relates to the antibody formulation prepared by the process and uses for this antibody formulation.
- Fig.l shows a typical flow through chromatogram of low pH hydrophobic interaction chromatography
- Fig.2 depicts a Reverse Phase HPLC analysis of ABXTM and Phenyl SepharoseTM Fast Flow (FF) pools ofanti-CD18 MHM23 antibody fragment.
- Chromatogram 1 ABX pool containing light and heavy chain contaminants present before LPHIC purification.
- Chromatogram 2 LPHIC purification.
- Chromatogram 3 Reverse Phase analysis of the column regeneration buffer containing light and heavy chain impurities and antibody fragments retained by the Phenyl Sepharose rM Fast Flow column.
- Figs. 3A-3D depict near UV and far UV spectra of two antibody fragments. rhuMAb H520ZG 1 and rhuMAb H520ZG2, obtained by circular dichroism.
- Fig. 3 A depicts near-UV spectra of rhuMAb H520ZG2
- Fig. 3B depicts far-UV spectra of rhuMAb H520ZG2.
- This antibody is a mutant of rhuMAb H520ZG 1 in which cysteine residues 215 and 228, involved in disulfide bonding between the heavy and light chains, were mutated to serine residues.
- Circular dichroism spectra in both the far and near UV regions showed a transition point around pH 3.2 (thick line).
- a transition point represents a change from folded antibody fragment, to its unfolded state.
- Fig. 3C is a near-UV spectra of rhuMAb H520ZG 1 and Fig. 3D is a far-UV spectra of rhuMAb
- Fig. 4 is a bar graph depicting the consequences on product yield of varying the HIC pH.
- ABXTM purified antibody fragment pools containing the linkless antibody impurity i.e. having no disulfide bond between the heavy and light chain
- the purification was performed at pH values between 3.0 and 6.5 in order to determine the best pH to obtain maximum yield and purity.
- Analysis of the flow through pools was performed using Reverse Phase HPLC. From the bar graph it can be seen that pH 3.1 represents the best value to maximize both purity and yield in the purification of rhuMAb H520ZG 1 antibody fragment.
- Figs. 5A and 5B depict L-F(ab')-> design and expression cassette described in Example 2 herein.
- Fig. 5A is a schematic representation of L-F(ab')2 variants (vl, v2 and v3) in which variable (V) domains from the anti-plSSTM 1 * 2 Ab, huMAb4D5-8, and from the anti-CD18 Ab, huMAb H520ZG1, are denoted by open and filled boxes, respectively.
- Fig. 5B is a schematic representation of the dicistronic operon for expression of anti-
- phoA E. coli alkaline phosphatase promoter
- (Ab) chain is preceded by the E. coli heat-stable enterotoxin II (stll) signal sequence to direct secretion to the periplasmic space of E. coli.
- the humanized V- ⁇ and V- ⁇ (both copies) domains are precisely fused on their 3' side to human K j C ⁇ and IgG j C- ⁇ l constant domains, respectively.
- the H chain comprises tandemly duplicated segments in which the 5' Cp j l domain is joined in frame to a Vp j encoding segment.
- the 3' C- ⁇ l domain is followed by the bacteriophage lambda tg transcriptional terminator (ter).
- Figs. 6A-6C depict FPLC size exclusion chromatography analysis of anti-pl 85* ⁇ .
- Fig. 6A shows L-F(ab') 2 vl ;
- Fig. 6B shows thioether linked F(ab') j and
- Fig. 6C shows Fab titration with pl 85 HER2 extracellular domain (ECD).
- Fig. 7 shows inhibition of proliferation of BT474 cells by anti-pl ss ⁇ - ⁇ 2 L-F(ab') 2 , F(ab') 2 and Fab fragments. Data shown are presented as a percentage of results with untreated cultures (mean of duplicate measurements and representative of three separate experiments). Monovalent and bivalent fragments as judged by titration with pl85 HFR2 ECD and gel filtration, are represented by open and closed symbols, respectively.
- Fig. 8 depicts pharmacokinetics of anti-pl 85 L-F(ab')2 vl , Fab and thioether-linked F(ab')2 fragments in normal mice. Serum samples were recovered from groups of 45 female CD-I mice after a single tail vein injection ( 10 mg kg). The mean serum concentrations (C t ⁇ SD) estimated by antigen (Ag)-binding
- antibody is used in the broadest sense and specifically covers intact monoclonal antibodies (including agonist and antagonist antibodies), polyclonal antibodies, multispecific antibodies (e.g. bispecific antibodies) formed from at least two intact antibodies, and antibody fragments so long as they exhibit the desired biological activity.
- Antibody fragments comprise a portion of an intact antibody, generally the antigen binding or variable region of the intact antibody.
- antibody fragments include Fab, Fab', and Fv fragments; diabodies; linear antibodies (see Example 2 below); single-chain antibody molecules; and multispecific antibodies formed from antibody fragments.
- the term "monoclonal antibody” as used herein refers to an antibody obtained from a population of substantially homogeneous antibodies, i.e., the individual antibodies comprising the population are identical except for possible naturally occurring mutations that may be present in minor amounts. Monoclonal antibodies are highly specific, being directed against a single antigenic site. Furthermore, in contrast to conventional (polyclonal) antibody preparations which typically include different antibodies directed against different determinants (epitopes), each monoclonal antibody is directed against a single determinant on the antigen. In addition to their specificity, the monoclonal antibodies are advantageous in that they are synthesized by the hybridoma culture, unconta inated by other immunoglobulins.
- the modifier "monoclonal” indicates the character of the antibody as being obtained from a substantially homogeneous population of antibodies, and is not to be construed as requiring production of the antibody by any particular method.
- the monoclonal antibodies to be used in accordance with the present invention may be made by the hybridoma method first described by Kohler and Milstein, Nature. 256:495 (1975), or may be made by recombinant DNA methods (see, e.g., U.S. Patent No. 4,816,567 [Cabilly et al.]).
- the "monoclonal antibodies” may also be isolated from phage antibody libraries using the techniques described in Clackson et al, Nature. 352:624-628 (1991 ) and Marks et al., J. Mol. BioL 222:581-597 ( 1991 ), for example.
- the monoclonal antibodies herein specifically include "chimeric" antibodies (immunoglobulins) in which a portion of the heavy and/or light chain is identical with or homologous to corresponding sequences in antibodies derived from a particular species or belonging to a particular antibody class or subclass, while the remainder of the chain(s) is identical with or homologous to corresponding sequences in antibodies derived from another species or belonging to another antibody class or subclass, as well as fragments of such antibodies, so long as they exhibit the desired biological activity (Cabilly et al, supra; Morrison et al, Proc. Natl. Acad. Sci. USA. 81 :6851-6855 [1984]).
- chimeric antibodies immunoglobulins in which a portion of the heavy and/or light chain is identical with or homologous to corresponding sequences in antibodies derived from a particular species or belonging to a particular antibody class or subclass, while the remainder of the chain(s) is identical with or homologous to corresponding sequences in antibodies
- Humanized forms of non-human ⁇ e.g., murine antibodies are chimeric immunoglobulins, immunoglobulin chains or fragments thereof (such as Fv, Fab, Fab', F(ab')-> or other antigen-binding subsequences of antibodies) which contain minimal sequence derived from non-human immunoglobulin.
- humanized antibodies are human immunoglobulins (recipient antibody) in which residues from a complementary-determining region (CDR) of the recipient are replaced by residues from a CDR of a non- human species (donor antibody) such as mouse, rat or rabbit having the desired specificity, affinity, and capacity.
- humanized antibodies may comprise residues which are found neither in the recipient antibody nor in the imported CDR or framework sequences. These modifications are made to further refine and optimize antibody performance.
- the humanized antibody will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the CDR regions correspond to those of a non-human immunoglobulin and all or substantially all of the FR regions are those of a human immunoglobulin sequence.
- the humanized antibody optimally also will comprise at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin.
- Fc immunoglobulin constant region
- the humanized antibody includes a PrimatizedTM antibody wherein the antigen-binding region of the antibody is derived from an antibody produced by immunizing macaque monkeys with the antigen of interest.
- diabodies refers to small antibody fragments with two antigen-binding sites, which fragments comprise a heavy-chain variable domain (V* ⁇ ) connected to a light-chain variable domain (Vi ) on the same polypeptide chain (V- ⁇ - V ⁇ ).
- V* ⁇ heavy-chain variable domain
- Vi light-chain variable domain
- linker that is too short to allow pairing between the two domains on the same chain, the domains are forced to pair with the complementary domains of another chain and create two antigen-binding sites.
- Diabodies are described more fully in, for example, EP 404,097; WO 93/1 1161; and Holliger et al, Proc. Natl. Acad. Sci. USA. 90:6444-6448 (1993).
- buffer refers to a buffered solution that resists changes in pH by the action of its acid-base conjugate components.
- the buffer for the hydrophobic interaction chromatography aspect of this invention has a pH in a range of about 2.5-4.5, preferably about 2.8-3.5.
- buffers that will control the pH within this range include phosphate, acetate, citrate or ammonium buffers, or more than one.
- the preferred such buffers are citrate and ammonium buffers, most preferably ammonium sulfate or ammonium citrate buffers.
- the "loading buffer” is that which is used to load the mixture of the antibody and contaminant
- SUBSTITUTE SHEET (RUU 26) on the HIC column and the "elution buffer” is that which is used to elute the antibody from the column. Often the loading buffer and elution buffer will be the same.
- correctly disulfide linked is meant that all cysteine residues in the antibody are covalently associated as disulfide bonds and these disulfide associations correspond to the disulfide associations of the native immunoglobulin.
- Circular dichroism as described in Example 1 may be used to determine whether or not an antibody is correctly disulfide linked by following the structural integrity of the molecule upon acid denaturation.
- An antibody is "incorrectly disulfide linked” when one or more cysteine residues are not covalently associated as disulfide bonds or are covalently associated with cysteine residues with which they are normally not associated in the native immunoglobulin.
- the process herein involves purifying an antibody from its related variants, usually after the antibody has already been purified from most other impurities.
- This purification step may be the final one before therapeutic formulation or it may be followed by other purification step(s).
- the antibody in the mixture of variants may be produced from any source (e.g. peptic cleavage of intact antibodies), preferably it is made recombinantly. Techniques for production of antibodies, including antibody fragments, follow.
- Polyclonal antibodies are generally raised in animals by multiple subcutaneous (sc) or intraperitoneal
- a protein that is immunogenic in the species to be immunized e.g., keyhole limpet hemocyanin, serum albumin, bovine thyroglobulin. or soybean trypsin inhibitor using a bifunctional or derivatizing agent, for example, male
- Animals are immunized against the antigen, immunogenic conjugates, or derivatives by combining 1 mg or 1 ⁇ g of the peptide or conjugate (for rabbits or mice, respectively) with 3 volumes of Freund's complete adjuvant and injecting the solution intradermally at multiple sites.
- 1 month later the animals are boosted with 1/5 to 1/10 the original amount of peptide or conjugate in Freund's complete adjuvant by subcutaneous injection at multiple sites.
- Seven to 14 days later the animals are bled and the serum is assayed for antibody titer. Animals are boosted until the titer plateaus.
- the animal is boosted with the conjugate of the same antigen, but conjugated to a different protein and/or through a different cross-linking reagent.
- Conjugates also can be made in recombinant cell culture as protein fusions. Also, aggregating agents such as alum are suitably used to enhance the immune response, (ii) Monoclonal antibodies
- Monoclonal antibodies are obtained from a population of substantially homogeneous antibodies, i.e., the individual antibodies comprising the population are identical except for possible naturally occurring mutations that may be present in minor amounts.
- the modifier "monoclonal" indicates the character of the antibody as not being a mixture of discrete antibodies.
- the monoclonal antibodies may be made using the hybridoma method first described by Kohler and Milstein, Nature. 256:495 (1975), or may be made by recombinant DNA methods (Cabilly et al, supra).
- a mouse or other appropriate host animal such as a hamster
- lymphocytes that produce or are capable of producing antibodies that will specifically bind to the protein used for immunization.
- lymphocytes may be immunized in vitro. Lymphocytes then are fused with myeloma cells using a suitable fusing agent, such as polyethylene glycol, to form a hybridoma cell (Goding, Monoclonal Antibodies: Principles and Practice, pp.59- 103 [Academic Press, 1986]).
- the hybridoma cells thus prepared are seeded and grown in a suitable culture medium that preferably contains one or more substances that inhibit the growth or survival of the unfused, parental myeloma cells.
- a suitable culture medium that preferably contains one or more substances that inhibit the growth or survival of the unfused, parental myeloma cells.
- the culture medium for the hybridomas typically will include hypoxanthine, aminopterin, and thymidine (HAT medium), which substances prevent the growth of HGPRT-deficient cells.
- Preferred myeloma cells are those that fuse efficiently, support stable high-level production of antibody by the selected antibody-producing cells, and are sensitive to a medium such as HAT medium.
- preferred myeloma cell lines are murine myeloma lines, such as those derived from MOPC-21 and MPC-1 1 mouse tumors available from the Salk Institute Cell Distribution Center, San Diego, California USA, and SP-2 cells available from the American Type Culture Collection, Rockville, Maryland USA.
- Human myeloma and mouse-human heteromyeloma cell lines also have been described for the production of human monoclonal antibodies (Kozbor, J. Immunol.. 133:3001 [1984]; Brön et al.
- Culture medium in which hybridoma cells are growing is assayed for production of monoclonal antibodies directed against the antigen.
- the binding specificity of monoclonal antibodies produced by hybridoma cells is determined by immunoprecipitation or by an in vitro binding assay, such as radioimmunoassay (RIA) or enzyme-linked immunoabsorbent assay (ELISA).
- the binding affinity of the monoclonal antibody can, for example, be determined by the Scatchard analysis of Munson and Pollard, Anal. Biochem.. 107:220 ( 1980).
- the clones may be subcloned by limiting dilution procedures and grown by standard methods (Goding, supra). Suitable culture media for this purpose include, for example, D-MEM or RPMI-1640 medium.
- the hybridoma cells may be grown in vivo as ascites tumors in an animal.
- the monoclonal antibodies secreted by the subclones are suitably separated from the culture medium, ascites fluid, or serum by conventional immunoglobulin purification procedures such as, for example, protein A-Sepharose , hydroxylapatite chromatography, gel electrophoresis, dialysis, or affinity chromatography.
- DNA encoding the monoclonal antibodies is readily isolated and sequenced using conventional procedures (e.g., by using oligonucleotide probes that are capable of binding specifically to genes encoding the heavy and light chains of murine antibodies).
- the hybridoma cells serve as a preferred source of such DNA.
- the DNA may be placed into expression vectors, which are then transfected into host cells such as E. coli cells, simian COS cells, Chinese hamster ovary (CHO) cells, or myeloma cells that do not otherwise produce immunoglobulin protein, to obtain the synthesis of monoclonal antibodies in the recombinant host cells.
- antibodies or antibody fragments can be isolated from antibody phage libraries generated using the techniques described in McCafferty et al, Nature. 348:552-554 (1990), using the proper antigen such as CDl la, CD18, IgE, or HER-2 to select for a suitable antibody or antibody fragment.
- Clackson et al, Nature.352:624-628 (1991 ) and Marks et al, J. Mol. BioL. 222:581 -597 (1991 ) describe the isolation of murine and human antibodies, respectively, using phage libraries.
- Subsequent publications describe the production of high affinity (nM range) human antibodies by chain shuffling (Mark et al, Bio/Technology.
- the DNA also may be modified, for example, by substituting the coding sequence for human heavy- and light-chain constant domains in place of the homologous murine sequences (Cabilly et al, supra; Morrison, et al, Proc. Nat. Acad. Sci.. 81:6851 [1984]), or by covalently joining to the immunoglobulin coding sequence all or part of the coding sequence for a non-immunoglobulin polypeptide.
- non-immunoglobulin polypeptides are substituted for the constant domains of an antibody, or they are substituted for the variable domains of one antigen-combining site of an antibody to create a chimeric bivalent antibody comprising one antigen-combining site having specificity for an antigen and another antigen-combining site having specificity for a different antigen.
- Chimeric or hybrid antibodies also may be prepared in vitro using known methods in synthetic protein chemistry, including those involving crosslinking agents.
- immunotoxins may be constructed using a disulfide-exchange reaction or by forming a thioether bond.
- suitable reagents for this purpose include iminothiolate and methyl-4-mercaptobutyrimidate.
- the variants herein derived from antibodies typically will be labeled with a detectable moiety.
- the detectable moiety can be any one which is capable of producing, either directly or indirectly, a detectable signal.
- the detectable moiety may be a radioisotope, such as J H, C, 3 P, 35 S, or 125 I; a fluorescent or chemiluminescent compound, such as fluorescein isothiocyanate, rhodamine, or luciferin; radioactive isotopic labels, such as, e.g., I, P, C, or H; or an enzyme, such as alkaline phosphatase, beta-galactosidase, or horseradish peroxidase.
- a radioisotope such as J H, C, 3 P, 35 S, or 125 I
- a fluorescent or chemiluminescent compound such as fluorescein isothiocyanate, rhodamine, or luciferin
- radioactive isotopic labels such as, e.g., I, P, C, or H
- an enzyme such as alkaline phosphatase, beta-galactosidase, or horseradish peroxidase
- a humanized antibody has one or more amino acid residues introduced into it from a source which is non-human. These non- human amino acid residues are often referred to as "import" residues, which are typically taken from an "import” variable domain.
- Humanization can be essentially performed following the method of Winter and co-workers (Jones et al, Nature. 321:522-525 [ 1986]: Riechmann et al, Nature. 332:323-327 [ 1988]; Verhoeyen et al, Science. 239: 1534-1536 [1988]), by substituting rodent CDRs or CDR sequences for the corresponding sequences of a human antibody.
- humanized antibodies are chimeric antibodies (Cabilly et al, supra), wherein substantially less than an intact human variable domain has been substituted by the corresponding sequence from a non-human species.
- humanized antibodies are typically human antibodies in which some CDR residues and possibly some FR residues are substituted by residues from analogous sites in rodent antibodies.
- variable domains both light and heavy
- the choice of human variable domains, both light and heavy, to be used in making the humanized antibodies is very important to reduce antigenicity.
- the sequence of the variable domain of a rodent antibody is screened against the entire library of known human variable- domain sequences.
- the human sequence which is closest to that of the rodent is then accepted as the human framework (FR) for the humanized antibody (Sims et al, J. Immunol.. 151 :2296 [1993]; Chothia and Lesk, J. Mol. BioL 196:901 [1987]).
- Another method uses a particular framework derived from the consensus sequence of all human antibodies of a particular subgroup of light or heavy chains.
- the same framework may be used for several different humanized antibodies (Carter et al, Proc. Natl. Acad. Sci. USA. 89:4285 [ 1992]; Presta et al, J. Immunol.. 151 :2623 [1993]).
- humanized antibodies are prepared by a process of analysis of the parental sequences and various conceptual humanized products using three-dimensional models of the parental and humanized sequences.
- Three-dimensional immunoglobulin models are commonly available and are familiar to those skilled in the art.
- Computer programs are available which illustrate and display probable three-dimensional conformational structures of selected candidate immunoglobulin sequences. Inspection of these displays permits analysis of the likely role of the residues in the functioning of the candidate immunoglobulin sequence, i.e.. the analysis of residues that influence the ability of the candidate immunoglobulin to bind its antigen.
- FR residues can be selected and combined from the consensus and import sequences so that the desired antibody characteristic, such as increased affinity for the target antigen(s), is achieved.
- the CDR residues are directly and most substantially involved in influencing antigen binding.
- transgenic animals e.g.. mice
- transgenic animals e.g.. mice
- the homozygous deletion of the antibody heavy-chain joining region (i ⁇ .) gene in chimeric and germ-line mutant mice results in complete inhibition of endogenous antibody production.
- Transfer of the human germ-line immunoglobulin gene array in such germ- line mutant mice will result in the production of human antibodies upon antigen challenge. See, e.g.,
- Bispecific antibodies are antibodies that have binding specificities for at least two different antigens.
- Bispecific antibodies can be derived from full length antibodies or antibody fragments (e.g. F(ab')2 bispecific antibodies).
- bispecific antibodies are known in the art. Traditional production of full length bispecific antibodies is based on the coexpression of two immunoglobulin heavy chain-light chain pairs, where the two chains have different specificities (Millstein and Cuello, Nature.305:537-539 [ 1983]). Because of the random assortment of immunoglobulin heavy and light chains, these hybridomas (quadromas) produce a potential mixture of 10 different antibody molecules, of which only one has the correct bispecific structure. Purification of the correct molecule, which is usually done by affinity chromatography steps, is rather cumbersome, and the product yields are low. Similar procedures are disclosed in WO 93/08829, published 13 May 1993. and in Traunecker et al. EMBO J.. 10:3655-3659 (1991).
- antibody variable domains with the desired binding specificities are fused to immunoglobulin constant domain sequences.
- the fusion preferably is with an immunoglobulin heavy chain constant domain, comprising at least part of the hinge, C ⁇ 2, and C- ⁇ 3 regions. It is preferred to have the first heavy-chain constant region (CJJ 1 ) containing the site necessary for light chain binding, present in at least one of the fusions.
- DNAs encoding the immunoglobulin heavy chain fusions and, if desired, the immunoglobulin light chain are inserted into separate expression vectors, and are co-transfected into a suitable host organism.
- the bispecific antibodies are composed of a hybrid immunoglobulin heavy chain with a first binding specificity in one arm. and a hybrid immunoglobulin heavy chain-light chain pair (providing a second binding specificity) in the other arm. It was found that this asymmetric structure facilitates the separation of the desired bispecific compound from unwanted immunoglobulin chain combinations, as the presence of an immunoglobulin light chain in only one half of the bispecific molecule provides for a facile way of separation. This approach is disclosed in WO 94/04690 published March 3, 1994. For further details of generating bispecific antibodies see, for example, Suresh et al, Methods in Enzvmologv. 121:210 (1986).
- Bispecific antibodies include cross-linked or "heteroconjugate" antibodies.
- one of the antibodies in the heteroconjugate can be coupled to avidin, the other to biotin.
- Such antibodies have, for example, been proposed to target immune system cells to unwanted cells (US Patent No. 4,676.980), and for treatment of HIV infection (WO 91/00360, WO 92/200373, and EP 03089).
- Heteroconjugate antibodies may be made using any convenient cross-linking methods. Suitable cross-linking agents are well known in the art, and are disclosed in US Patent No. 4,676.980, along with a number of cross-linking techniques. Techniques for generating bispecific antibodies from antibody fragments have also been described in the literature.
- bispecific antibodies can be prepared using chemical linkage.
- Brennan et al. Science. 229:81 (1985) describe a procedure wherein intact antibodies are proteolytically cleaved to generate F(ab')-) fragments. These fragments are reduced in the presence of the dithiol complexing agent sodium arsenite to stabilize vicinal dithiols and prevent intermolecular disulfide formation.
- the Fab' fragments generated are then converted to thionitrobenzoate (TNB) derivatives.
- One of the Fab'-TNB derivatives is then reconverted to the Fab'-thiol by reduction with mercaptoethylamine and is mixed with an equimolar amount of the other Fab'-TNB derivative to form the BsAb.
- the BsAbs produced can be used as agents for the selective immobilization of enzymes.
- bispecific F(ab')2 heterodimers have been produced using leucine zippers.
- the leucine zipper peptides from the Fos and Jun proteins were linked to the Fab' portions of two different antibodies by gene fusion.
- the antibody homodimers were reduced at the hinge region to form monomers and then re-oxidized to form the antibody heterodimers.
- the "diabody” technology described by Hollinger et al, Proc. Natl. Acad. Sci. (USA).
- the fragments comprise a heavy-chain variable domain (V* ⁇ ) connected to a light-chain variable domain (V- ⁇ ) by a linker which is too short to allow pairing between the two domains on the same chain Accordingly, the V j _ j and V- ⁇ domains of one fragment are forced to pair with the complementary V ⁇ and V* ⁇ domains of another fragment, thereby forming two antigen-binding sites
- V* ⁇ heavy-chain variable domain
- V- ⁇ light-chain variable domain
- the antibody can be produced lntracellularly, in the pe ⁇ plasmic space, or directly secreted into the medium If the antibody is produced lntracellularly, as a first step, the paniculate debris, either host cells or lysed fragments, is removed, for example, by centrifugation or ultrafiltration Carter et al , Bio echnologv 10 163-167 (1992) describe a procedure for isolating antibodies which are secreted to the pe ⁇ plasmic space of £ coli Briefly, cell paste is thawed in the presence of sodium acetate (pH 3 5), EDTA, and phenylmethylsulfonylfluo ⁇ de (PMSF) over about 30 min Cell debris can be removed by cent ⁇ fugation Where the antibody is secreted into the medium, supematants from such expression systems are generally first concentrated using a commercially available protein concentration filter, for example, an Amicon or Milhpore Pelhcon ultrafiltration unit A protease inhibitor such as
- the antibody composition prepared from the cells is preferably subjected to at least one purification step prior to LPHIC
- suitable purification steps include hydroxylapatite chromatography, gel electrophoresis, dialysis, and affinity chromatography, with affinity chromatography being the preferred pu ⁇ fication technique
- affinity chromatography being the preferred pu ⁇ fication technique
- the suitability of protein A as an affinity ligand depends on the species and isotype of any immunoglobulin Fc domain that is present in the antibody Protein A can be used to purify antibodies that are based on human ⁇ 1 , ⁇ 2, or ⁇ 4 heavy chains (Lindmark et al , J.
- Protein G is recommended for all mouse isotypes and for human ⁇ 3 (Guss et al , EMBO J 5 15671575 [ 1986])
- the matrix to which the affinity ligand is attached is most often agarose, but other matrices are available Mechanically stable mat ⁇ ces such as controlled pore glass or poly(styrened ⁇ v ⁇ nyl)benzene allow for faster flow rates and shorter processing times than can be achieved with agarose
- the Bakerbond ABX resin J T Baker, Phil psburg, NJ
- Other techniques for protem purification such as fractionation on an ion-exchange column, ethanol precipitation, Reverse Phase HPLC, chromatography on silica, chromatography on hepa ⁇ n Sepharose , chromatography on an anion or cation exchange resin (such as a polyaspartic acid column), chromatofocusing, SDS-PAGE,
- the mixture comprising the antibody of interest and contam ⁇ nant(s) is subjected to LPHIC Often, the antibody composition to be pu ⁇ fied will be present in a buffer from the previous purification step However, it may be necessary to add a buffer to the antibody composition p ⁇ or to the LPHIC step Many buffers are available and can be selected by routine experimentation
- the pH of the mixture comprising the antibody to be purified and at least one contaminant in a loading buffer is adjusted to a pH of about 2 5-4 5 using either an acid or base, depending on the starting pH
- the loading buffer has a low salt concentration (/ e less than about 0 25M salt)
- the mixture is loaded on the HIC column HIC columns normally comp ⁇ se a base at ⁇ x (e g cross- linked agarose or synthetic copolymer material) to which hydrobobic ligands (e g alkyl or aryl groups) are coupled
- the preferred HIC column comprises an agarose resm substituted with
- the antibody composition prepared by LPHIC can be further purified as desired using techniques which are well known in the art Diagnostic or therapeutic formulations of the purified protein can be made by providing the antibody composition in a physiologically acceptable earner, examples of which are provided below To remove contaminants (e g unfolded antibody and incorrectly associated light and heavy fragments) from the HIC column so that it can be re-used, a composition including urea (e g 6 0 M urea, 1% MES buffer pH 6 0, 4mM ammonium sulfate) can be flowed through the column
- urea e g 6 0 M urea, 1% MES buffer pH 6 0, 4mM ammonium sulfate
- BsAbs are particularly useful for this type of assay, one arm of the BsAb can be designed to bind to a specific epitope on the enzyme so that binding does not cause enzyme inhibition, the other arm of the antibody can be designed to bind to an immobilizing matrix ensuring a high enzyme density at the desired site
- diagnostic BsAbs include those having specificity for IgG as well as femtin. and those having binding specificities for horseradish peroxidase (HRP) as well as a hormone, for example
- the antibodies can be designed for use in two-site immunoassays For example, two antibodies are produced binding to two separate epitopes on the analyte protein, one antibody binds the complex to an insoluble matrix, the other binds an indicator enzyme
- Antibodies can also be used for in vitro or in vrvo immunodiagnosis of various diseases such as cancer
- an antibody which binds a tumor associated antigen can be conjugated with a detectable marker (c g a chelator which binds a radionuclide)
- a detectable marker c g a chelator which binds a radionuclide
- a antibody having specificity for the tumor associated antigen CEA can be used for imaging of coiorectal and thryroid carcinomas
- the anti- pl85 antibodv disclosed herein can be used for detecting cancers characterized by amplification of the HER2 protooncogene
- Other non-therapeutic, diagnostic uses for the antibody will be apparent to the skilled practitioner
- the antibody typically will be labeled directly or indirectly with a detectable moiety
- the detectable moiety can be any one which is capable of producing, either directly or indirectly, a detectable signal
- the detectable moiety may be a radioisotope, such as 3 H, C, J ⁇ P, JJ S, or 1.
- a fluorescent or chemiluminescent compound such as fluorescein isothiocyanate, rhodamine, or lucife ⁇ n
- an enzyme such as alkaline phosphatase, beta-galactosidase or HRP
- the antibodies of the present invention may be employed m any known assay method, such as competitive binding assays, direct and indirect sandwich assays, and lmmunoprecipitation assays Zola, Monoclonal Antibodies. A Manual of Techniques, pp 147-158 (CRC Press, lnc , 1987)
- the antibodies also are useful for the affinity purification of an antigen of interest from recombinant cell culture or natural sources
- the antibody can be used for redirected cytotoxicity (e g to kill tumor cells), as a vaccine adjuvant, for delivering thrombolytic agents to clots, for delivering lmmunotoxins to tumor cells, for converting enzyme activated prodrugs at a target site (e g a tumor), for treating infectious diseases or targeting immune complexes to cell surface receptors
- cytotoxicity e g to kill tumor cells
- thrombolytic agents e.g to kill tumor cells
- lmmunotoxins e.g to kill tumor cells
- therapeutic formulations of the antibody are prepared for storage by mixing the antibody having the desired degree of purity with optional physiologically acceptable carriers, excipients or stabilizers (Remington's Pharmaceutical Sciences 16th edition.
- Acceptable earners excipients or stabilizers are nontoxic to recipients at the dosages and concentrations employed, and include buffers such as phosphate, citrate, and other organic acids, antioxidants including ascorbic acid, low molecular weight (less than about 10 residues) polypeptides, proteins, such as serum albumin, gelatin, or immunoglobulins, hydrophilic polymers such as polyvin lpyrro done, ammo acids such as glycine, glutamme, asparagine, arginine or lysine.
- buffers such as phosphate, citrate, and other organic acids
- antioxidants including ascorbic acid, low molecular weight (less than about 10 residues) polypeptides, proteins, such as serum albumin, gelatin, or immunoglobulins, hydrophilic polymers such as polyvin lpyrro done, ammo acids such as glycine, glutamme, asparagine, arginine or lysine.
- the antibody also may be entrapped in microcapsules prepared, for example, by coacervation techniques or by interfacial polymerization (for example, hydroxymethylcellulose or gelatin-microcapsules and poly-[methylmethacylate] microcapsules, respectively), in colloidal drug delivery systems (for example, liposomes. albumin microspheres, microemulsions, nano-particles and nanocapsules), or in macroemulsions Such techniques are disclosed in Remington's Pharmaceutical Sciences, supra
- the antibody to be used for in vivo administration must be sterile This is readily accomplished by filtration through sterile filtration membranes, prior to or following lyophilization and reconstitution The antibody ordinarily will be stored in lyophilized form or in solution
- Therapeutic antibody compositions generally are placed into a container havmg a sterile access port, for example, an mtravenous solution bag or vial havmg a stopper pierceable by a hypodermic mjection needle
- the route of antibody administration is in accord with known methods, e g , mjection or infusion by mtravenous. lntrape ⁇ toneal, mtracerebral, intramuscular, intraocular, intraarterial, or intralesional routes, or by sustained release systems as noted below
- the antibody is administered contmuously by infusion or by bolus mjection
- sustained-release preparations mclude semipermeable matrices of solid hydrophobic polymers containing the protem, which mat ⁇ ces are in the form of shaped articles, e g , films, or microcapsules
- sustained-release mat ⁇ ces include polyesters, hydrogels [e g , poly(2- hydroxyethyl-methacrylate) as desc ⁇ bed by Langer et al , J.
- degradable lactic acid-glycolic acid copolymers such as the Lupron Depot TM (injectable microspheres composed of lactic acid-glycolic acid copolymer and leuprolide acetate), and poly-D-(-)-3-hydroxybutyric acid (EP 133,988). While polymers such as ethylene-vinyl acetate and lactic acid-glycolic acid enable release of molecules for over 100 days, certain hydrogels release proteins for shorter time periods. When encapsulated antibodies remain in the body for a long time, they may denature or aggregate as a result of exposure to moisture at 37°C, resulting in a loss of biological activity and possible changes in immunogenicity.
- Rational strategies can be devised for antibody stabilization depending on the mechanism involved. For example, if the aggregation mechanism is discovered to be mtermolecular S-S bond formation through thio-disulfide interchange, stabilization may be achieved by modifying sulfhydryl residues, lyophilizing from acidic solutions, controlling moisture content, using appropriate additives, and developing specific polymer matrix compositions.
- Sustained-release antibody compositions also include liposomally entrapped antibody.
- Liposomes containing the antibody are prepared by methods known per se: DE 3,218.121 ; Epstein et al , Proc. Natl. Acad. Sci. USA 82:3688-3692 (1985); Hwang et al. Proc. Natl. Acad. Sci. USA 77:4030-4034 (1980); EP 52.322: EP 36,676; EP 88,046; EP 143.949; EP 142,641 ; Japanese patent application 83-1 18008; U.S. Patent Nos. 4.485,045 and 4,544,545; and EP 102,324.
- the liposomes are of the small (about 200-800 Angstroms) unilamellar type in which the lipid content is greater than about 30 mol. % cholesterol, the selected proportion being adjusted for the optimal antibody therapy.
- An effective amount of antibody to be employed therapeutically will depend, for example, upon the therapeutic objectives, the route of administration, and the condition of the patient. Accordingly, it will be necessary for the therapist to titer the dosage and modify the route of administration as required to obtain the optimal therapeutic effect.
- a typical daily dosage might range from about 1 ⁇ g/kg to up to 10 mg/kg or more, depending on the factors mentioned above.
- the clinician will administer antibody until a dosage is reached that achieves the desired effect. The progress of this therapy is easily monitored by conventional assays.
- Reverse Phase Chromatography Analysis Reverse Phase chromatography was earned out on a Reverse Phase PLRP-STM 4 6 x 50mm column, 8mm particle size, (Polymer Laboratories, Shropshire, UK) maintained at 50°C
- the proteins were eluted using an increasing linear gradient from 31 % Buffer B to 41 % Buffer B Buffer A contained 0 1% trifluoroacetic acid in deionized water, and Buffer B contained 0 1% tnfluoroacetic acid in HPLC grade acetonit ⁇ le
- the flow rate was maintained at 2ml m ⁇ n, and the detection wavelength was 214 nm
- ABXTM chromatography The supernatant containing the antibody fragment was diluted to a conductivity of 2 milhsiemens or less with purified water The diluted supernatant was pumped sequentially through 0 5 and 022 micron filters and loaded onto a ABXTM column (J T Baker Phillipsburg, NJ) equilibrated in 50 mM MES/5mM EDTA, pH 6.0 (Buffer A). The effluent was monitored at 280 run. After loading, the column was washed with Buffer A for 2 column volumes. Antibodies were eluted with a 20 column volume gradient from 0 to 50 mM ammonium sulfate in Buffer A. Fractions were analyzed by HPLC and pooled accordingly. 5 Low pH Hydrophobic Interaction Chromatography (LPHIC). The ABX T purified Fab' pools
- Circular Dichroism Spectra was recorded on an AVIV model 60DS instrument at 25°C. Path length cells of 1mm were used for far UV measurements and 10 mm path length cells for near UV measurements.
- the rhuMAb H520ZG 1 and rhuMAb H520ZG2 purified antibody samples were buffer exchanged into 1 OmM 0 PO4 buffer by gel permeation chromatography on Sephadex G25TM (Pharmacia Biotech Inc. Piscataway, NJ). The samples were titrated with phosphoric acid to desired pH prior to measuring the CD spectra.
- the ABXTM purified pool 5 appears to contain small amounts of antibody fragments whose light and heavy chains are correctly folded but fail to covalently associate through a disulfide bond. This impurity can be detected on SDS gels and by analytical Reverse Phase HPLC (Fig. 2).
- the non-covalently associated antibody fragments can be separated from the desired product by preferential acid denaturation followed by LPHIC. To determine the acid denaturation differences between the disulfide associated and non disulfide associated species two purified 0 antibody fragments were used; rhuMAb H520ZG2 and rhuMAb H520ZG 1.
- RhuMAb H520ZG2 is a mutant of rhuMAb H520ZG 1 in which the cysteine residues 215 and 228 in the light and the heavy chains respectively have been changed to serine residues. This mutant should mimic the acid denaturation behavior of non disulfide linked antibodies.
- Near-UV and far-UV spectra of rhuMAb H520ZG2 and rhuMAb H520ZG1 at different pH values show different denaturation transition points (Figs. 3A-3D).
- a transition point represents 5 a change from correctly folded antibody fragment, to its unfolded state.
- Non disulfide associated fragments can be denatured around pH 3.2, whereas the disulfide associated fragments required pH values below 2.5 for denaturation.
- This example desc ⁇ bes the production of bivalent, linear (L-)F(ab')2 fragments (comprising tandem repeats of a heavy chain fragment, V j ⁇ -C* ⁇ 1 -V ⁇ -C ⁇ 1 cosecreted with a light chain) which were subjected to LPHIC (see Example 1 above).
- L-F(ab')2 variants The expression plasmid. pAK19, for secretion of huMAb4D5-8 Fab' fragment has previously been described (Carter et al , Bio Technologv 10 163-167 [ 1992]) Plasmids pLAl, pLA2 and pLA3 were designed to secrete L-F(ab')2 variants vl , v2 and v3, respectively (Fig. 5A).
- Plasmid pLAl was constructed from pAK19 by modifying the heavy cha to encode tandem huMAb4D5- 8 Fd segments: V- ⁇ -C ⁇ 1 - H -C* ⁇ 1 L-F(ab') 7 v2 and v3 were constructed from pLA 1 by precisely replacing 5' or 3' copies of V- ⁇ in pLAl, respectively, with that from the humanized ant ⁇ -CD18 Ab, huMAb H520Z (Eigenbrot et al, supra) A plasmid was designed to secrete L-F(ab')- anti-CD 18 A plasmid was constructed from anti-CD 18 Ab, huMAb H520Z (Eigenbrot et al , supra) by modifying the heavy chain to encode tandem Fd segments jj -C jj 1 -V j -C jj 1 E.
- L-F(ab' variants were purified from 400g of corresponding fermentation pastes thawed in the presence of 2 liters 20mM MES, 5 mM EDTA, pH 6.0 (ME buffer) Resuspended cells were disrupted by three passages through a microfluidizer (Microfluidics Corporation, Newton , MA) and adjusted to 0.25 % (v/v) polyethyleneimine Solid debris was removed by centrifugation (7,300g. 30 in, 4°C) The supernatant was diluted with an equal volume of distilled water and then loaded onto a 20 ml Bakerbond ABX column (J T Baker. Phillipsburg, NJ) pre-equilibrated with ME buffer.
- L-F(ab')-> was eluted using a linear gradient of 0-50 mM (NH 4 S0 4 in ME buffer. Pooled L-F(ab')-, was adjusted to 25 mM Na->HP0 4 , pH 3 0 and passed over a 20 ml Phenyl Sepharose M Fast Flow column (high sub) (Pharmacia, Piscataway, NJ) equilibrated with 25 mM Na->HP0 4 , 20 mM (NH 4 )-,S0 4 , pH 3.0. The flow through fractions contammg L-F(ab')-, were pooled and adjusted to pH 6.0.
- L-F(ab')-> variants were designed to comprise a heavy (H) chain of tandem Fd fragments, V j -C ⁇ l-V jj -C ⁇ l, associated with two copies of the corresponding light (L) chain (Fig. 5A).
- H heavy
- V j -C ⁇ l-V jj -C ⁇ l heavy chain of tandem Fd fragments
- V j -C ⁇ l-V jj -C ⁇ l associated with two copies of the corresponding light (L) chain
- Fig. 5A the C-terminus of C ⁇ l (... THT) is joined directly to the N-terminus of V ⁇ (EVQ ...) without any extraneous linking protein sequences.
- huMAb4D5-8 L-F(ab')-> variant, vl was designed to have two functional binding sites for the Ag, pl 85 HER2 ECD (pj g 5A ) ln contrast huMAb4D5-8 L-F(ab') 2 v2 and v3 were designed to have a single Ag binding site. This was accomplished by replacing either 5' or 3' copies of ⁇ - in L-F(ab')2 vl with that from the anti-CDl 8 Ab, huMAbH52 OZ (Eigenbrot et al, supra). A Fab comprising the L chain from huMAb4D5-8 and the H chain Fd fragment from huMAbH52 OZ was expressed and purified and found to not bind p l 85 HER2 ECD as anticipated.
- L-F(ab')-, variants were expressed in £. coli by cosecretion of the L chain with the tandem H chain Fd fragments from a dicistronic operon (Fig. 5B). Titers of ⁇ 100 mg/l functional (Ag-binding) huMAb4D5-8 L-F(ab')2 were achieved following culturing of £. coli containing corresponding expression plasmids to high cell density in the fermentor. L-F(ab')2 were recovered directly from E. coli by fully disrupting corresponding fermentation
- L-F(ab')--) and F(ab')-> give rise to a band of -48 kDa as anticipated from the presence of tandem and thioether-linked H chain dimers, respectively.
- the reduced H and L chains for the Fab fragment are not resolved under the electrophoretic conditions used.
- HFR* Analysis of binding of Ab fragments to pl85 ECD.
- the stoichiometry of the Ab-Ag interaction was investigated by titration of huMAb4D5-8 Ab fragments with pi 85 ⁇ ECD followed by size exclusion chromatographic analysis (Figs. 6A-6C).
- huMAb4D5-8 L-F(ab')-> vl and F(ab')-> show very similar titration profiles with pi 85 ECD and bind two equivalents of antigen (Figs. 6A and 6B).
- the Fab fragment binds one equivalent of Ag (Fig. 6C).
- L-F(ab')-, v2 and v3 bind only a single equivalent of
- the bivalent L-F(ab')2 variant, vl binds Ag with 3-fold lower affinity than the does F(ab')2- This mainly reflects a small decrease in association rate between F(ab')-*, and L-F(ab')2, respectively.
- the monovalent L-F(ab')2 variants v2 and v3 show approximately 3-fold and 12-fold weaker binding than the bivalent L-F(ab' *> variant, vl .
- both binding sites in the L-F(ab'>2 are ECD, although the efficiency of Ag binding is apparently slightly impaired for the C-terminal site.
- the binding affinity of L-F(ab')-, v2 is very similar to the corresponding Fab fragment.
- the antiproliferative activity of huMAb4D5-8 Ab fragments was investigated using the pl85" -overexpressing breast tumor cell line, BT474 (see Fig. 7). Proliferation of BT474 in the presence of saturating quantities of L-F(ab'>2 vl and thioether-linked F(ab' 2 are approximately 40% and 55% of the untreated control, respectively. Thus L-F(ab' 2 vl is more potent in blocking the proliferation of BT474 cells than is the thioether-linked F(ab')2 fragment.
- the terminal half-life contributes 83%, 30% and 6.5% to the total AUC for L-F(ab') 2 vl, F(ab') 2 and Fab, respectively.
- L-F(ab')2 and thioether-linked F(ab')2 are very similar in terms of their pharmacokinetic parameters, while the Fab fragment is cleared more rapidly.
- the permanence times in serum for L-F(ab')2 vl and thioether- linked F(ab')2 fragments, are 7-fold and 8-fold greater than for the Fab fragment, respectively.
- Glu Trp lie Gly Gly Phe Asn Pro Lys Asn Gly Gly Ser Ser His 50 55 60
Abstract
Description
Claims
Priority Applications (8)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DK96912575T DK0821695T3 (en) | 1995-04-20 | 1996-04-05 | Purification of antibody by hydrophobic interaction chromatography at low pH |
DE69636733T DE69636733T2 (en) | 1995-04-20 | 1996-04-05 | ANTIBODY PURIFICATION BY HYDROPHOBIC INTERACTION CHROMATOGRAPHY AT LOW PH |
EP96912575A EP0821695B1 (en) | 1995-04-20 | 1996-04-05 | Antibody purification by low-ph hydrophobic interaction chromatography |
NZ306718A NZ306718A (en) | 1995-04-20 | 1996-04-05 | Antibody purification by low-ph hydrophobic interaction chromatography (lphic) |
JP53177496A JP4042868B2 (en) | 1995-04-20 | 1996-04-05 | Antibody purification |
CA002214633A CA2214633C (en) | 1995-04-05 | 1996-04-05 | Antibody purification by low-ph hydrophobic interaction chromatography |
MX9707909A MX9707909A (en) | 1995-04-20 | 1996-04-05 | Antibody purification by low-ph hydrophobic interaction chromatoggraphy. |
AU55349/96A AU721736B2 (en) | 1995-04-20 | 1996-04-05 | Antibody purification by low-pH hydrophobic interaction chromatography |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US08/425,763 | 1995-04-20 | ||
US08/425,763 US5641870A (en) | 1995-04-20 | 1995-04-20 | Low pH hydrophobic interaction chromatography for antibody purification |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1996033208A1 true WO1996033208A1 (en) | 1996-10-24 |
Family
ID=23687930
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1996/004683 WO1996033208A1 (en) | 1995-04-05 | 1996-04-05 | Antibody purification by low-ph hydrophobic interaction chromatoggraphy |
Country Status (16)
Country | Link |
---|---|
US (5) | US5641870A (en) |
EP (2) | EP1752465B1 (en) |
JP (3) | JP4042868B2 (en) |
AT (2) | ATE346858T1 (en) |
AU (1) | AU721736B2 (en) |
CA (1) | CA2214633C (en) |
DE (1) | DE69636733T2 (en) |
DK (2) | DK1752465T3 (en) |
ES (2) | ES2365929T3 (en) |
HK (1) | HK1099310A1 (en) |
IL (1) | IL117942A (en) |
MX (1) | MX9707909A (en) |
NZ (2) | NZ306718A (en) |
PT (1) | PT821695E (en) |
WO (1) | WO1996033208A1 (en) |
ZA (1) | ZA962885B (en) |
Cited By (35)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1999057134A1 (en) * | 1998-05-06 | 1999-11-11 | Genentech, Inc. | Protein purification by ion exchange chromatography |
WO2001064711A1 (en) * | 2000-03-02 | 2001-09-07 | Kyowa Hakko Kogyo Co., Ltd. | Method of separating and purifying protein |
EP1308456A2 (en) * | 1998-05-06 | 2003-05-07 | Genentech, Inc. | Antibody purification by ion exchange chromatography |
EP1333032A1 (en) * | 2000-10-06 | 2003-08-06 | Kyowa Hakko Kogyo Co., Ltd. | Method of purifying antibody |
WO2004087761A1 (en) * | 2003-03-31 | 2004-10-14 | Kirin Beer Kabushiki Kaisha | Purification of human monoclonal antibody and human polyclonal antibody |
US7064191B2 (en) | 2000-10-06 | 2006-06-20 | Kyowa Hakko Kogyo Co., Ltd. | Process for purifying antibody |
EP1687328A1 (en) * | 2003-10-24 | 2006-08-09 | Amgen, Inc. | Process for purifying proteins in a hydrophobic interaction chromatography flow-through fraction |
AU2003200708B2 (en) * | 1998-05-06 | 2007-01-04 | Genentech, Inc. | Protein purification |
EP2004689A4 (en) * | 2006-04-05 | 2010-06-02 | Abbott Biotech Ltd | Antibody purification |
EP2344532A1 (en) | 2008-10-06 | 2011-07-20 | MSD Biologics (UK) Limited | Purification process for fragment antibodies |
EP2565206A2 (en) | 2007-10-30 | 2013-03-06 | Genentech, Inc. | Antibody purification by cation exchange chromatography |
US8921526B2 (en) | 2013-03-14 | 2014-12-30 | Abbvie, Inc. | Mutated anti-TNFα antibodies and methods of their use |
US8946395B1 (en) | 2013-10-18 | 2015-02-03 | Abbvie Inc. | Purification of proteins using hydrophobic interaction chromatography |
US9017687B1 (en) | 2013-10-18 | 2015-04-28 | Abbvie, Inc. | Low acidic species compositions and methods for producing and using the same using displacement chromatography |
US9062106B2 (en) | 2011-04-27 | 2015-06-23 | Abbvie Inc. | Methods for controlling the galactosylation profile of recombinantly-expressed proteins |
US9067990B2 (en) | 2013-03-14 | 2015-06-30 | Abbvie, Inc. | Protein purification using displacement chromatography |
US9085618B2 (en) | 2013-10-18 | 2015-07-21 | Abbvie, Inc. | Low acidic species compositions and methods for producing and using the same |
US9150645B2 (en) | 2012-04-20 | 2015-10-06 | Abbvie, Inc. | Cell culture methods to reduce acidic species |
US9181337B2 (en) | 2013-10-18 | 2015-11-10 | Abbvie, Inc. | Modulated lysine variant species compositions and methods for producing and using the same |
US9181572B2 (en) | 2012-04-20 | 2015-11-10 | Abbvie, Inc. | Methods to modulate lysine variant distribution |
US9193787B2 (en) | 2012-04-20 | 2015-11-24 | Abbvie Inc. | Human antibodies that bind human TNF-alpha and methods of preparing the same |
US9206390B2 (en) | 2012-09-02 | 2015-12-08 | Abbvie, Inc. | Methods to control protein heterogeneity |
US9234033B2 (en) | 2012-09-02 | 2016-01-12 | Abbvie, Inc. | Methods to control protein heterogeneity |
US9249182B2 (en) | 2012-05-24 | 2016-02-02 | Abbvie, Inc. | Purification of antibodies using hydrophobic interaction chromatography |
US9499614B2 (en) | 2013-03-14 | 2016-11-22 | Abbvie Inc. | Methods for modulating protein glycosylation profiles of recombinant protein therapeutics using monosaccharides and oligosaccharides |
US9526768B2 (en) | 2014-11-13 | 2016-12-27 | Jennifer Mai | Compositions for the treatment of cancer |
US9550826B2 (en) | 2013-11-15 | 2017-01-24 | Abbvie Inc. | Glycoengineered binding protein compositions |
US9598667B2 (en) | 2013-10-04 | 2017-03-21 | Abbvie Inc. | Use of metal ions for modulation of protein glycosylation profiles of recombinant proteins |
US10023608B1 (en) | 2013-03-13 | 2018-07-17 | Amgen Inc. | Protein purification methods to remove impurities |
CN111479829A (en) * | 2017-11-01 | 2020-07-31 | 中外制药株式会社 | Antibody variants and isotypes with reduced biological activity |
US11214623B2 (en) | 2014-09-26 | 2022-01-04 | Chugai Seiyaku Kabushiki Kaisha | Antibody capable of neutralizing substance having activity alternative to function of coagulation factor VIII (FVIII) |
US11248053B2 (en) | 2007-09-26 | 2022-02-15 | Chugai Seiyaku Kabushiki Kaisha | Method of modifying isoelectric point of antibody via amino acid substitution in CDR |
US11352438B2 (en) | 2016-09-06 | 2022-06-07 | Chugai Seiyaku Kabushiki Kaisha | Methods of using a bispecific antibody that recognizes coagulation factor IX and/or activated coagulation factor IX and coagulation factor X and/or activated coagulation factor X |
US11649262B2 (en) | 2015-12-28 | 2023-05-16 | Chugai Seiyaku Kabushiki Kaisha | Method for promoting efficiency of purification of Fc region-containing polypeptide |
RU2813990C2 (en) * | 2017-11-01 | 2024-02-21 | Чугаи Сейяку Кабусики Кайся | Versions and isoforms of antibodies with reduced biological activity |
Families Citing this family (1078)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
SG43125A1 (en) * | 1993-10-27 | 1997-10-17 | Molex Inc | Shunted electrical connector |
US5641870A (en) * | 1995-04-20 | 1997-06-24 | Genentech, Inc. | Low pH hydrophobic interaction chromatography for antibody purification |
US20040121415A1 (en) * | 1996-12-10 | 2004-06-24 | King David John | Monovalent antibody fragments |
US8088386B2 (en) | 1998-03-20 | 2012-01-03 | Genentech, Inc. | Treatment of complement-associated disorders |
AU784157B2 (en) | 1999-06-25 | 2006-02-16 | Genentech Inc. | Methods of treatment using anti-ErbB antibody-maytansinoid conjugates |
HU226742B1 (en) | 1999-06-25 | 2009-08-28 | Genentech Inc | Humanized anti-erbb2 antibodies and treatment with anti-erbb2 antibodies |
JP2001066308A (en) * | 1999-07-29 | 2001-03-16 | Gsf Forschungszentrum Fuer Umwelt & Gesundheit Gmbh | DETECTION OF IRREVERSIBLE INJURY OF IgG ANTIBODY |
WO2001035735A1 (en) * | 1999-11-19 | 2001-05-25 | Hematech, Llc | Production of ungulates, preferably bovines that produce human immunoglobulins |
US7074983B2 (en) * | 1999-11-19 | 2006-07-11 | Kirin Beer Kabushiki Kaisha | Transgenic bovine comprising human immunoglobulin loci and producing human immunoglobulin |
US7414170B2 (en) * | 1999-11-19 | 2008-08-19 | Kirin Beer Kabushiki Kaisha | Transgenic bovines capable of human antibody production |
US7820878B2 (en) * | 1999-11-19 | 2010-10-26 | Kyowa Hakko Kirin Co., Ltd. | Production of ungulates, preferably bovines that produce human immunoglobulins |
US20030023043A1 (en) * | 2000-03-02 | 2003-01-30 | Kazuhisa Uchida | Method of separating and purifying protein |
LT2857516T (en) * | 2000-04-11 | 2017-09-11 | Genentech, Inc. | Multivalent antibodies and uses therefor |
EP1299128A2 (en) | 2000-06-20 | 2003-04-09 | Idec Pharmaceuticals Corporation | Cold anti-cd20 antibody/radiolabeled anti-cd22 antibody combination |
US6984522B2 (en) * | 2000-08-03 | 2006-01-10 | Regents Of The University Of Michigan | Isolation and use of solid tumor stem cells |
DE60139944D1 (en) | 2000-10-12 | 2009-10-29 | Genentech Inc | LOW VISCOSIS CONCENTRATED PROTEIN FORMULATIONS |
US6979556B2 (en) * | 2000-12-14 | 2005-12-27 | Genentech, Inc. | Separate-cistron contructs for secretion of aglycosylated antibodies from prokaryotes |
US20020159996A1 (en) | 2001-01-31 | 2002-10-31 | Kandasamy Hariharan | Use of CD23 antagonists for the treatment of neoplastic disorders |
US20070160576A1 (en) | 2001-06-05 | 2007-07-12 | Genentech, Inc. | IL-17A/F heterologous polypeptides and therapeutic uses thereof |
US20060270003A1 (en) | 2003-07-08 | 2006-11-30 | Genentech, Inc. | IL-17A/F heterologous polypeptides and therapeutic uses thereof |
CA2633171C (en) | 2001-06-20 | 2012-11-20 | Genentech, Inc. | Antibodies against tumor-associated antigenic target (tat) polypeptides |
US6867189B2 (en) | 2001-07-26 | 2005-03-15 | Genset S.A. | Use of adipsin/complement factor D in the treatment of metabolic related disorders |
NZ530852A (en) * | 2001-08-27 | 2006-11-30 | Genentech Inc | Methods and compositions for recombinantly producing functional antibodies or antibody fragments in prokaryotic and eukaryotic host cells |
US20040235068A1 (en) * | 2001-09-05 | 2004-11-25 | Levinson Arthur D. | Methods for the identification of polypeptide antigens associated with disorders involving aberrant cell proliferation and compositions useful for the treatment of such disorders |
NZ573831A (en) | 2001-09-18 | 2010-07-30 | Genentech Inc | Compositions and methods for the diagnosis and treatment of tumor, particularly breast tumor - TAT193 |
US20050123925A1 (en) | 2002-11-15 | 2005-06-09 | Genentech, Inc. | Compositions and methods for the diagnosis and treatment of tumor |
NZ533933A (en) | 2002-01-02 | 2008-06-30 | Genentech Inc | Compositions and methods for the diagnosis and treatment of glioma tumor |
US8658773B2 (en) | 2011-05-02 | 2014-02-25 | Immunomedics, Inc. | Ultrafiltration concentration of allotype selected antibodies for small-volume administration |
US20160279239A1 (en) | 2011-05-02 | 2016-09-29 | Immunomedics, Inc. | Subcutaneous administration of anti-cd74 antibody for systemic lupus erythematosus and autoimmune disease |
AU2003224916B2 (en) | 2002-04-10 | 2009-01-08 | Genentech, Inc. | Anti-HER2 antibody variants |
CA2481507A1 (en) | 2002-04-16 | 2003-10-30 | Genentech, Inc. | Compositions and methods for the diagnosis and treatment of tumor |
EP1532453B1 (en) * | 2002-05-31 | 2013-08-21 | Genetic Technologies Limited | Maternal antibodies as fetal cell markers to identify and enrich fetal cells from maternal blood |
EP2305710A3 (en) | 2002-06-03 | 2013-05-29 | Genentech, Inc. | Synthetic antibody phage libraries |
JP5069843B2 (en) | 2002-07-15 | 2012-11-07 | ジェネンテック, インコーポレイテッド | Method for identifying tumors responsive to treatment with anti-ErbB2 antibodies |
ZA200501839B (en) * | 2002-08-29 | 2006-10-25 | Genentech Inc | Achaete-scute like-2 polypeptides and encoding nucleic acids and methods for the diagnosis and treatment of tumor |
ATE489400T1 (en) * | 2002-09-06 | 2010-12-15 | Genentech Inc | PROTEIN EXTRACTION METHOD |
US9453251B2 (en) | 2002-10-08 | 2016-09-27 | Pfenex Inc. | Expression of mammalian proteins in Pseudomonas fluorescens |
WO2004035608A2 (en) * | 2002-10-18 | 2004-04-29 | Abgenix, Inc. | System and method for cleaving antibodies |
CA2502490A1 (en) * | 2002-11-08 | 2004-05-27 | Hematech, Llc | Transgenic ungulates having reduced prion protein activity and uses thereof |
WO2004092393A1 (en) | 2003-01-09 | 2004-10-28 | Genentech, Inc. | Purification of polypeptides |
US8394582B2 (en) * | 2003-03-05 | 2013-03-12 | Genetic Technologies, Inc | Identification of fetal DNA and fetal cell markers in maternal plasma or serum |
PT1610820E (en) | 2003-04-04 | 2010-12-16 | Novartis Ag | High concentration antibody and protein formulations |
RS51686B (en) | 2003-04-09 | 2011-10-31 | Genentech Inc. | Therapy of autoimmune disease in a patient with an inadequate response to a tnf-alpha inhibitor |
UA101945C2 (en) | 2003-05-30 | 2013-05-27 | Дженентек, Инк. | Treatment of cancer using bevacizumab |
WO2005000896A2 (en) * | 2003-05-30 | 2005-01-06 | Genentech, Inc. | Polypeptides that bind an anti-tissue factor antibody and uses thereof |
PT1631313E (en) | 2003-06-05 | 2015-07-02 | Genentech Inc | Combination therapy for b cell disorders |
JP5068072B2 (en) * | 2003-06-27 | 2012-11-07 | バイオジェン・アイデック・エムエイ・インコーポレイテッド | Modified binding molecule comprising a linking peptide |
US20050165222A1 (en) * | 2003-10-15 | 2005-07-28 | Applera Corporation | Method of reducing leachate from protein a affinity media |
BR122018071808B8 (en) | 2003-11-06 | 2020-06-30 | Seattle Genetics Inc | conjugate |
US20050214805A1 (en) * | 2003-11-10 | 2005-09-29 | Q-Rna, Inc. | Methods of detection employing immuno-Q-Amp technology |
PT2161283E (en) | 2003-11-17 | 2014-08-29 | Genentech Inc | Compositions comprising antibodies against cd79b conjugated to a growth inhibitory agent or cytotoxic agent and methods for the treatment of tumor of hematopoietic origin |
US20060122784A1 (en) * | 2004-12-03 | 2006-06-08 | Ishikawa Muriel Y | System and method for augmenting a humoral immune response |
US20060095211A1 (en) * | 2003-12-05 | 2006-05-04 | Searete Llc, A Limited Liability Corporation Of The State Of Delaware | System and method for modulating a cell mediated immune response |
US20060047434A1 (en) * | 2004-08-24 | 2006-03-02 | Ishikawa Muriel Y | System and method related to improving an immune system |
US20060047437A1 (en) * | 2004-08-25 | 2006-03-02 | Ishikawa Muriel Y | System and method for heightening an immune response |
US20060122783A1 (en) * | 2004-08-24 | 2006-06-08 | Ishikawa Muriel Y | System and method for heightening a humoral immune response |
US20060116824A1 (en) * | 2004-12-01 | 2006-06-01 | Ishikawa Muriel Y | System and method for modulating a humoral immune response |
US20060047435A1 (en) * | 2004-08-24 | 2006-03-02 | Ishikawa Muriel Y | System and method related to augmenting an immune system |
US20060182742A1 (en) * | 2004-08-24 | 2006-08-17 | Ishikawa Muriel Y | System and method for magnifying a humoral immune response |
US20060047436A1 (en) * | 2004-08-25 | 2006-03-02 | Ishikawa Muriel Y | System and method for magnifying an immune response |
WO2005073711A2 (en) * | 2004-01-20 | 2005-08-11 | Pall Corporation | Chromatographic material for the absorption of proteins at physiological ionic strength |
WO2005087812A1 (en) * | 2004-03-05 | 2005-09-22 | Ludwig Institute For Cancer Research | Multivalent antibody materials and methods for vegf/pdgf family of growth factors |
AU2005230848B9 (en) | 2004-03-31 | 2011-06-02 | Genentech, Inc. | Humanized anti-TGF-beta antibodies |
US20060002930A1 (en) * | 2004-04-16 | 2006-01-05 | Genentech, Inc. | Treatment of disorders |
US20150017671A1 (en) | 2004-04-16 | 2015-01-15 | Yaping Shou | Methods for detecting lp-pla2 activity and inhibition of lp-pla2 activity |
JP2007532681A (en) * | 2004-04-16 | 2007-11-15 | ジェネンテック・インコーポレーテッド | Methods for increasing B cell depletion |
JP2007533328A (en) * | 2004-04-22 | 2007-11-22 | キリンホールディングス株式会社 | Transgenic animals and uses thereof |
BRPI0510883B8 (en) | 2004-06-01 | 2021-05-25 | Genentech Inc | drug-antibody conjugate compound, pharmaceutical composition, method of manufacturing a drug-antibody conjugate compound, and uses of a formulation, a drug-antibody conjugate and a chemotherapeutic agent, and a combination |
TW201422238A (en) | 2004-06-04 | 2014-06-16 | Genentech Inc | Use of CD20 antibody in treatment of multiple sclerosis and an article for the use |
ES2339789T3 (en) * | 2004-07-20 | 2010-05-25 | Genentech, Inc. | PROTEIN 4 INHIBITORS OF ANGIOPOYETINE TYPE, COMBINATIONS AND ITS USE. |
US8604185B2 (en) | 2004-07-20 | 2013-12-10 | Genentech, Inc. | Inhibitors of angiopoietin-like 4 protein, combinations, and their use |
JP2008507294A (en) | 2004-07-26 | 2008-03-13 | ダウ グローバル テクノロジーズ インコーポレイティド | Method for improved protein expression by strain genetic manipulation |
US20070265788A1 (en) * | 2004-08-24 | 2007-11-15 | Searete Llc, A Limited Liability Corporation Of The State Of Delaware | Computational methods and systems for augmenting cell-mediated immune response |
US20070196362A1 (en) * | 2004-08-24 | 2007-08-23 | Searete Llc, A Limited Liability Corporation Of The State Of Delaware | Computational methods and systems to bolster an immune response |
US20070265819A1 (en) * | 2004-08-24 | 2007-11-15 | Searete Llc, A Limited Liability Corporation Of The State Of Delaware | Computational methods and systems for improving cell-mediated immune response |
US20070207492A1 (en) * | 2004-08-24 | 2007-09-06 | Searete Llc, A Limited Liability Corporation Of The State Of Delaware | Computational methods and systems to adjust a humoral immune response |
US20060047439A1 (en) * | 2004-08-24 | 2006-03-02 | Searete Llc, A Limited Liability Corporation Of The State Of Delaware | System and method for improving a humoral immune response |
US20070198196A1 (en) * | 2004-08-24 | 2007-08-23 | Searete Llc, A Limited Liability Corporation Of The State Of Delaware | Computational systems and methods relating to ameliorating an immune system |
US20070265817A1 (en) * | 2004-08-24 | 2007-11-15 | Searete Llc, A Limited Liability Corporation Of The State Of Delaware | Computational systems and methods relating to fortifying an immune system |
US20070265818A1 (en) * | 2004-08-24 | 2007-11-15 | Searete Llc, A Limited Liability Corporation Of The State Of Delaware | Computational methods and systems for heightening cell-mediated immune response |
US20070265787A1 (en) * | 2004-08-24 | 2007-11-15 | Searete Llc,A Limited Liability Corporation Of The State Of Delaware | Computational methods and systems for magnifying cell-mediated immune response |
US20070288173A1 (en) * | 2004-08-24 | 2007-12-13 | Searete Llc, A Limited Liability Corporation Of The State Of Delware | Computational methods and systems to reinforce a humoral immune response |
US20060051347A1 (en) | 2004-09-09 | 2006-03-09 | Winter Charles M | Process for concentration of antibodies and therapeutic products thereof |
JO3000B1 (en) | 2004-10-20 | 2016-09-05 | Genentech Inc | Antibody Formulations. |
RS52539B (en) | 2004-10-21 | 2013-04-30 | Genentech Inc. | Method for treating intraocular neovascular diseases |
WO2006074399A2 (en) * | 2005-01-05 | 2006-07-13 | Biogen Idec Ma Inc. | Multispecific binding molecules comprising connecting peptides |
DE602006013275D1 (en) | 2005-01-07 | 2010-05-12 | Diadexus Inc | OVR110 ANTIBODY COMPOSITIONS AND USER METHOD THEREFOR |
KR20190110637A (en) | 2005-01-21 | 2019-09-30 | 제넨테크, 인크. | Fixed dosing of her antibodies |
RU2404806C2 (en) | 2005-02-23 | 2010-11-27 | Дженентек, Инк. | Extension of time to progression of disease or lifetime of oncologic patients with application of her dimerisation inhibitors |
TW200714289A (en) * | 2005-02-28 | 2007-04-16 | Genentech Inc | Treatment of bone disorders |
US20160355591A1 (en) | 2011-05-02 | 2016-12-08 | Immunomedics, Inc. | Subcutaneous anti-hla-dr monoclonal antibody for treatment of hematologic malignancies |
US20060204505A1 (en) * | 2005-03-08 | 2006-09-14 | Sliwkowski Mark X | Methods for identifying tumors responsive to treatment with HER dimerization inhibitors (HDIs) |
PT1869065T (en) | 2005-03-11 | 2020-06-18 | Wyeth Llc | A method of weak partitioning chromatography |
EP1879923B1 (en) | 2005-04-09 | 2015-05-27 | Fusion Antibodies Limited | Cathepsin s antibody |
NZ563341A (en) | 2005-06-06 | 2009-10-30 | Genentech Inc | Methods for identifying agents that modulate a gene that encodes for a PRO1568 polypeptide |
WO2007008848A2 (en) | 2005-07-07 | 2007-01-18 | Seattle Genetics, Inc. | Monomethylvaline compounds having phenylalanine carboxy modifications at the c-terminus |
JP5171621B2 (en) | 2005-07-07 | 2013-03-27 | シアトル ジェネティックス, インコーポレイテッド | Monomethylvaline compound having phenylalanine side chain modification at C-terminus |
AU2006280321A1 (en) | 2005-08-15 | 2007-02-22 | Genentech, Inc. | Gene disruptions, compositions and methods relating thereto |
US7612181B2 (en) | 2005-08-19 | 2009-11-03 | Abbott Laboratories | Dual variable domain immunoglobulin and uses thereof |
US20090215992A1 (en) * | 2005-08-19 | 2009-08-27 | Chengbin Wu | Dual variable domain immunoglobulin and uses thereof |
EP2500358A3 (en) | 2005-08-19 | 2012-10-17 | Abbott Laboratories | Dual variable domain immunoglobulin and uses thereof |
WO2007024715A2 (en) | 2005-08-19 | 2007-03-01 | Abbott Laboratories | Dual variable domain immunoglobin and uses thereof |
US9119828B2 (en) * | 2005-09-23 | 2015-09-01 | The United States Of America As Represented By The Secretary Of The Army | Antibodies with simultaneous subsite specificities to protein and lipid epitopes |
US7422899B2 (en) * | 2005-10-05 | 2008-09-09 | Biogen Idec Ma Inc. | Antibodies to the human prolactin receptor |
WO2007053577A2 (en) | 2005-10-31 | 2007-05-10 | Oncomed Pharmaceuticals, Inc. | Compositions and methods for diagnosing and treating cancer |
WO2007056411A2 (en) * | 2005-11-08 | 2007-05-18 | Genentech, Inc. | Method of producing pan-specific antibodies |
MY149159A (en) | 2005-11-15 | 2013-07-31 | Hoffmann La Roche | Method for treating joint damage |
ZA200804162B (en) | 2005-11-21 | 2009-12-30 | Genentech Inc | Novel gene disruptions, compositions and methods relating thereto |
ES2547689T3 (en) | 2005-12-02 | 2015-10-08 | Genentech, Inc. | Compositions and methods for the treatment of diseases and disorders associated with cytokine signaling that involve antibodies that bind to IL-22 and IL-22R |
ES2535856T3 (en) | 2005-12-15 | 2015-05-18 | Genentech, Inc. | Methods and compositions for targeting polyubiquitin |
US7625759B2 (en) | 2005-12-19 | 2009-12-01 | Genentech, Inc. | Method for using BOC/CDO to modulate hedgehog signaling |
EP1973950B1 (en) | 2006-01-05 | 2014-09-17 | Genentech, Inc. | Anti-ephb4 antibodies and methods using the same |
WO2007114979A2 (en) | 2006-02-17 | 2007-10-11 | Genentech, Inc. | Gene disruptons, compositions and methods relating thereto |
AR059851A1 (en) | 2006-03-16 | 2008-04-30 | Genentech Inc | ANTIBODIES OF EGFL7 AND METHODS OF USE |
TWI397535B (en) | 2006-03-21 | 2013-06-01 | Genentech Inc | Combinatorial therapy involving alpha5beta1 antagonists |
CA2647107A1 (en) | 2006-03-23 | 2007-09-27 | Novartis Ag | Anti-tumor cell antigen antibody therapeutics |
CA2647277A1 (en) | 2006-04-05 | 2007-11-08 | Genentech, Inc. | Method for using boc/cdo to modulate hedgehog signaling |
DE102006017701A1 (en) * | 2006-04-15 | 2007-10-25 | Degussa Gmbh | Silicon-titanium mixed oxide powder, dispersion thereof and titanium-containing zeolite produced therefrom |
US20090288176A1 (en) | 2006-04-19 | 2009-11-19 | Genentech, Inc. | Novel Gene Disruptions, Compositions and Methods Relating Thereto |
WO2007134132A2 (en) * | 2006-05-12 | 2007-11-22 | Genentech, Inc. | Compositions and methods for the diagnosis and treatment of bladder and urinary tract tumors |
CA2652945C (en) | 2006-05-30 | 2015-06-02 | Genentech, Inc. | Antibodies and immunoconjugates and uses therefor |
US8124743B2 (en) * | 2006-06-01 | 2012-02-28 | President And Fellows Of Harvard College | Purification of a bivalently active antibody using a non-chromatographic method |
US8874380B2 (en) | 2010-12-09 | 2014-10-28 | Rutgers, The State University Of New Jersey | Method of overcoming therapeutic limitations of nonuniform distribution of radiopharmaceuticals and chemotherapy drugs |
RU2499001C2 (en) | 2006-06-30 | 2013-11-20 | Ново Нордиск А/С | Antibodies to nkg2a and their applications |
MX2009000696A (en) | 2006-07-19 | 2009-01-30 | Univ Pennsylvania | Wsx-1/p28 as a target for anti-inflammatory responses. |
CA2660286A1 (en) | 2006-08-09 | 2008-02-21 | Homestead Clinical Corporation | Organ-specific proteins and methods of their use |
WO2008023840A2 (en) | 2006-08-25 | 2008-02-28 | Oncotherapy Science, Inc. | Prognostic markers and therapeutic targets for lung cancer |
EP2059533B1 (en) | 2006-08-30 | 2012-11-14 | Genentech, Inc. | Multispecific antibodies |
TW201708537A (en) | 2006-09-13 | 2017-03-01 | 艾伯維有限公司 | Cell culture improvements |
US8911964B2 (en) | 2006-09-13 | 2014-12-16 | Abbvie Inc. | Fed-batch method of making human anti-TNF-alpha antibody |
US20080076139A1 (en) | 2006-09-21 | 2008-03-27 | Sharat Singh | Methods and compositions for detecting the activation states of multiple signal transducers in rare circulating cells |
WO2011008990A1 (en) | 2009-07-15 | 2011-01-20 | Prometheus Laboratories Inc. | Drug selection for gastric cancer therapy using antibody-based arrays |
ME02371B (en) | 2006-09-29 | 2016-06-20 | Oncomed Pharm Inc | Compositions and methods for diagnosing and treating cancer |
WO2008063776A2 (en) * | 2006-10-12 | 2008-05-29 | Genentech, Inc. | Antibodies to lymphotoxin-alpha |
PT2502938E (en) | 2006-10-27 | 2015-06-05 | Genentech Inc | Antibodies and immunoconjugates and uses therefor |
JP5732196B2 (en) * | 2006-11-01 | 2015-06-10 | バイオジェン アイデック エムエー インコーポレイティドBiogen Idec Inc. | Method for isolating biopolymers using low pH and divalent cations |
US20080108147A1 (en) * | 2006-11-03 | 2008-05-08 | Tie Wei | Reduction of non-specific binding in immunoassays |
EP3156415A1 (en) | 2006-11-22 | 2017-04-19 | Bristol-Myers Squibb Company | Targeted therapeutics based on engineered proteins for tyrosine kinases receptors, including igf-ir |
WO2008067283A2 (en) | 2006-11-27 | 2008-06-05 | Diadexus, Inc. | Ovr110 antibody compositions and methods of use |
US20090186034A1 (en) * | 2006-12-19 | 2009-07-23 | Genetech, Inc. | Gene expression markers for inflammatory bowel disease |
WO2008079322A1 (en) * | 2006-12-22 | 2008-07-03 | Beckman Coulter, Inc. | Methods, kits and materials for diagnosing disease states by measuring isoforms or proforms of myeloperoxidase |
WO2008079849A2 (en) * | 2006-12-22 | 2008-07-03 | Genentech, Inc. | Antibodies to insulin-like growth factor receptor |
AU2008209404B2 (en) * | 2007-01-22 | 2012-08-16 | Genentech, Inc. | Polyelectrolyte precipitation and purification of antibodies |
US8148147B2 (en) * | 2007-01-24 | 2012-04-03 | The Regents Of The University Of Michigan | Compositions and methods for treating and diagnosing pancreatic cancer |
JP2010517944A (en) * | 2007-01-26 | 2010-05-27 | バイオインヴェント インターナショナル アーベー | DLL4 signaling inhibitor and use thereof |
CA2676766A1 (en) | 2007-02-09 | 2008-08-21 | Genentech, Inc. | Anti-robo4 antibodies and uses therefor |
WO2008100578A2 (en) * | 2007-02-14 | 2008-08-21 | Amgen Inc. | Method of isolating antibodies by precipitation |
WO2008103962A2 (en) | 2007-02-22 | 2008-08-28 | Genentech, Inc. | Methods for detecting inflammatory bowel disease |
PE20090681A1 (en) | 2007-03-02 | 2009-06-10 | Genentech Inc | PREDICTION OF RESPONSE TO A HER INHIBITOR |
CA2683977C (en) | 2007-03-14 | 2017-04-25 | Ligocyte Pharmaceuticals, Inc. | A method of norovirus virus-like particle purification comprising ion exchange chromatography |
US7960139B2 (en) | 2007-03-23 | 2011-06-14 | Academia Sinica | Alkynyl sugar analogs for the labeling and visualization of glycoconjugates in cells |
BRPI0810120A2 (en) | 2007-04-27 | 2014-11-11 | Dow Global Technologies Inc | PROCESS TO QUICKLY SELECT MICROBIAN HOST FOR THE IDENTIFICATION OF CERTAIN BETTER YIELDS AND / OR QUALITY IN EXPRESSION OF HETEROLOGICAL PROTEINS |
US9580719B2 (en) | 2007-04-27 | 2017-02-28 | Pfenex, Inc. | Method for rapidly screening microbial hosts to identify certain strains with improved yield and/or quality in the expression of heterologous proteins |
ES2433967T3 (en) | 2007-05-14 | 2013-12-13 | The University Of Chicago | Antibody-LIGHT fusion products as cancer therapeutic products |
WO2008154249A2 (en) | 2007-06-08 | 2008-12-18 | Genentech, Inc. | Gene expression markers of tumor resistance to her2 inhibitor treatment |
SI2173379T1 (en) | 2007-07-02 | 2015-12-31 | Oncomed Pharmaceuticals, Inc. | Compositions and methods for treating and diagnosing cancer |
CN101802013B (en) | 2007-07-16 | 2014-07-02 | 健泰科生物技术公司 | Humanized anti-CD79b antibodies and immunoconjugates and methods of use |
NZ583367A (en) | 2007-07-16 | 2012-10-26 | Genentech Inc | Anti-cd79b antibodies and immunoconjugates and methods of use |
JP2010535032A (en) * | 2007-07-31 | 2010-11-18 | メディミューン,エルエルシー | Multispecific epitope binding proteins and uses thereof |
EP3492488A1 (en) | 2007-08-22 | 2019-06-05 | The Regents of The University of California | Activatable binding polypeptides and methods of identification and use thereof |
US20110152345A1 (en) | 2007-08-24 | 2011-06-23 | Oncotherapy Science, Inc. | Ebi3, dlx5, nptx1 and cdkn3 for target genes of lung cancer therapy and diagnosis |
WO2009028158A1 (en) | 2007-08-24 | 2009-03-05 | Oncotherapy Science, Inc. | Dkk1 oncogene as therapeutic target for cancer and a diagnosing marker |
JP2010536365A (en) | 2007-08-24 | 2010-12-02 | オンコセラピー・サイエンス株式会社 | PKIB and NAALADL2 for prostate cancer therapeutic and diagnostic target genes |
CN101842387B (en) | 2007-09-26 | 2014-05-07 | Ucb医药有限公司 | Dual specificity antibody fusions |
CA2699601A1 (en) | 2007-10-02 | 2009-04-09 | Genentech, Inc. | Nlrr-1 antagonists and uses thereof |
WO2009045897A1 (en) * | 2007-10-03 | 2009-04-09 | Dyax Corp. | Systems and methods for purifying proteins |
AU2008312406B2 (en) | 2007-10-16 | 2014-03-06 | Ares Trading S.A. | Combination of BLyS inhibition and anti-CD 20 agents for treatment of autoimmune disease |
CN101951954A (en) | 2007-11-02 | 2011-01-19 | 诺瓦提斯公司 | Molecules and methods for modulating low-density-lipoprotein receptor-related protein 6 (LRP6) |
LT2514436T (en) | 2007-11-07 | 2018-04-10 | Genentech, Inc. | Il-22 for use in treating microbial disorders |
US20110033476A1 (en) * | 2007-11-12 | 2011-02-10 | Theraclone Sciences Inc. | Compositions and methods for the therapy and diagnosis of influenza |
WO2010135521A2 (en) | 2009-05-20 | 2010-11-25 | Theraclone Sciences, Inc. | Compositions and methods for the therapy and diagnosis of influenza |
KR20100097691A (en) | 2007-11-12 | 2010-09-03 | 테라클론 사이언시스, 아이엔씨. | Compositions and methods for the therapy and diagnosis of influenza |
CN101970689A (en) | 2007-11-29 | 2011-02-09 | 健泰科生物技术公司 | Gene expression markers for inflammatory bowel disease |
TWI580694B (en) | 2007-11-30 | 2017-05-01 | 建南德克公司 | Anti-vegf antibodies |
GB0723797D0 (en) | 2007-12-05 | 2008-01-16 | Immunosolv Ltd | Method |
TWI468174B (en) | 2007-12-14 | 2015-01-11 | Novo Nordisk As | Antibodies against human kng2d and uses thereof |
ES2626634T3 (en) | 2007-12-19 | 2017-07-25 | The Henry M. Jackson Foundation For The Advancement Of Military Medicine, Inc. | Soluble forms of Hendra and Nipah virus F glycoprotein and uses thereof |
EP2077281A1 (en) | 2008-01-02 | 2009-07-08 | Bergen Teknologioverforing AS | Anti-CD20 antibodies or fragments thereof for the treatment of chronic fatigue syndrome |
US7914785B2 (en) | 2008-01-02 | 2011-03-29 | Bergen Teknologieverforing As | B-cell depleting agents, like anti-CD20 antibodies or fragments thereof for the treatment of chronic fatigue syndrome |
AR070141A1 (en) * | 2008-01-23 | 2010-03-17 | Glenmark Pharmaceuticals Sa | SPECIFIC HUMANIZED ANTIBODIES FOR VON WILLEBRAND FACTOR |
JP5774312B2 (en) | 2008-01-24 | 2015-09-09 | ノボ・ノルデイスク・エー/エス | Humanized anti-human NKG2A monoclonal antibody |
TWI472339B (en) | 2008-01-30 | 2015-02-11 | Genentech Inc | Composition comprising antibody that binds to domain ii of her2 and acidic variants thereof |
MX2010008437A (en) | 2008-01-31 | 2010-11-25 | Genentech Inc | Anti-cd79b antibodies and immunoconjugates and methods of use. |
KR20100128291A (en) | 2008-02-14 | 2010-12-07 | 브리스톨-마이어스 스큅 컴퍼니 | Targeted therapeutics based on engineered proteins that bind egfr |
DK2602623T3 (en) | 2008-02-25 | 2015-11-09 | Nestec Sa | METHOD OF DETECTING INTRACELLULAR TRUNCTED RECEPTORS |
US20110092452A1 (en) * | 2008-03-05 | 2011-04-21 | The Regents Of The University Of Michigan | Compositions and methods for diagnosing and treating pancreatic cancer |
MX2010009885A (en) | 2008-03-10 | 2010-11-30 | Theraclone Sciences Inc | Compositions and methods for the therapy and diagnosis of cytomegalovirus infections. |
JP2011516078A (en) | 2008-04-10 | 2011-05-26 | セル・シグナリング・テクノロジー・インコーポレイテツド | Compositions and methods for detecting EGFR mutations in cancer |
CA2720048A1 (en) * | 2008-04-16 | 2009-10-22 | Biogen Idec Ma Inc. | Method of isolating biomacromolecules using polyalkylene glycol and transition metals |
NZ588554A (en) | 2008-04-29 | 2013-03-28 | Abbott Lab | Dual variable domain immunoglobulins and uses thereof |
US20100260668A1 (en) * | 2008-04-29 | 2010-10-14 | Abbott Laboratories | Dual Variable Domain Immunoglobulins and Uses Thereof |
WO2009136892A1 (en) | 2008-05-09 | 2009-11-12 | Akonni Biosystems | Microarray system |
US8680025B2 (en) * | 2008-05-09 | 2014-03-25 | Akonni Biosystems, Inc. | Microarray system |
US8093018B2 (en) | 2008-05-20 | 2012-01-10 | Otsuka Pharmaceutical Co., Ltd. | Antibody identifying an antigen-bound antibody and an antigen-unbound antibody, and method for preparing the same |
JP2011520961A (en) | 2008-05-22 | 2011-07-21 | ブリストル−マイヤーズ スクイブ カンパニー | Scaffold domain protein based on multivalent fibronectin |
CN102112494A (en) | 2008-06-03 | 2011-06-29 | 雅培制药有限公司 | Dual variable domain immunoglobulins and uses thereof |
AR072001A1 (en) | 2008-06-03 | 2010-07-28 | Abbott Lab | IMMUNOGLOBULIN WITH DUAL VARIABLE DOMAIN AND USES OF THE SAME |
EP2313507A2 (en) * | 2008-07-03 | 2011-04-27 | Pfenex Inc | High throughput screening method and use thereof to identify a production platform for a multifunctional binding protein |
WO2010006060A2 (en) * | 2008-07-08 | 2010-01-14 | Abbott Laboratories | Prostaglandin e2 dual variable domain immunoglobulins and uses thereof |
CN102112490B (en) | 2008-07-08 | 2014-10-22 | 昂考梅德药品有限公司 | Notch1 receptor binding agents and methods of use thereof |
US8680020B2 (en) | 2008-07-15 | 2014-03-25 | Academia Sinica | Glycan arrays on PTFE-like aluminum coated glass slides and related methods |
DK2328616T3 (en) | 2008-08-05 | 2015-07-20 | Novartis Ag | Compositions and Methods for Antibodies to Complement Protein C5 |
US8652843B2 (en) | 2008-08-12 | 2014-02-18 | Oncomed Pharmaceuticals, Inc. | DDR1-binding agents and methods of use thereof |
US8790642B2 (en) | 2008-08-29 | 2014-07-29 | Genentech, Inc. | Cross-reactive and bispecific anti-IL-17A/F antibodies |
AR073538A1 (en) | 2008-09-03 | 2010-11-17 | Genentech Inc | MULTI-SPECIFIC ANTIBODIES THAT SPECIFICALLY JOIN THE RECEPTOR OF THE HUMAN EPIDERMIC GROWTH FACTOR 2 (HER2) AND THE VASCULAR ENDOTELIAL GROWTH FACTOR (VEGF) |
EP2684570A1 (en) | 2008-09-10 | 2014-01-15 | F. Hoffmann-La Roche AG | Compositions and methods for the prevention of oxidative degradation of proteins |
TW201438738A (en) | 2008-09-16 | 2014-10-16 | Genentech Inc | Methods for treating progressive multiple sclerosis |
DK2334705T3 (en) * | 2008-09-26 | 2017-03-27 | Ucb Biopharma Sprl | BIOLOGICAL PRODUCTS |
KR102100066B1 (en) | 2008-10-14 | 2020-04-10 | 제넨테크, 인크. | Immunoglobulin variants and uses thereof |
CN104974251A (en) | 2008-10-20 | 2015-10-14 | Abbvie公司 | Viral inactivation during purification of antibodies |
AU2009347206C1 (en) | 2008-10-20 | 2016-12-08 | Abbvie Inc. | Isolation and purification of antibodies using Protein A affinity chromatography |
CN104634972B (en) | 2008-11-11 | 2017-06-13 | 密执安大学评议会 | Anti- CXCR1 compositions and method |
TW201029663A (en) * | 2008-11-12 | 2010-08-16 | Theraclone Sciences Inc | Human M2e peptide immunogens |
CA2742871C (en) | 2008-11-13 | 2018-10-23 | Herb Lin | Methods and compositions for regulating iron homeostasis by modulation of bmp-6 |
JP6041489B2 (en) | 2008-11-22 | 2016-12-07 | ジェネンテック, インコーポレイテッド | Use of anti-VEGF antibodies in combination with chemotherapy for the treatment of breast cancer |
WO2010062858A1 (en) * | 2008-11-26 | 2010-06-03 | Allergan, Inc. | Il-17 antibody inhibitor for treating dry eye |
US8211434B2 (en) * | 2008-11-26 | 2012-07-03 | Allergan, Inc. | KLK-13 antibody inhibitor for treating dry eye |
RU2011127198A (en) * | 2008-12-04 | 2013-01-10 | Эбботт Лэборетриз | IMMUNOGLOBULINS WITH DOUBLE VARIABLE DOMAINS AND THEIR APPLICATION |
BRPI0917592B1 (en) | 2008-12-09 | 2021-08-17 | Genentech, Inc | ANTI-PD-L1 ANTIBODY, COMPOSITION, MANUFACTURED ARTICLES AND USES OF A COMPOSITION |
SG172219A1 (en) | 2008-12-17 | 2011-07-28 | Genentech Inc | Hepatitis c virus combination therapy |
WO2010075249A2 (en) | 2008-12-22 | 2010-07-01 | Genentech, Inc. | A method for treating rheumatoid arthritis with b-cell antagonists |
BRPI0918204A2 (en) | 2008-12-23 | 2015-12-08 | Genentech Inc | igv variant pharmaceutical composition and kit |
US20110142836A1 (en) * | 2009-01-02 | 2011-06-16 | Olav Mella | B-cell depleting agents for the treatment of chronic fatigue syndrome |
BRPI1006141B8 (en) * | 2009-01-12 | 2021-05-25 | Cytomx Therapeutics Llc | modified antibody compositions, methods of making and using the same |
GB0902916D0 (en) | 2009-02-20 | 2009-04-08 | Fusion Antibodies Ltd | Antibody therapy |
EP2398829A2 (en) * | 2009-02-23 | 2011-12-28 | Glenmark Pharmaceuticals S.A. | Humanized antibodies that bind to cd19 and their uses |
CA2753294A1 (en) | 2009-02-23 | 2010-08-26 | Cytomx Therapeutics, Inc. | Proproteins and methods of use thereof |
GB0903168D0 (en) | 2009-02-25 | 2009-04-08 | Fusion Antibodies Ltd | Diagnostic method and kit |
JP5836807B2 (en) | 2009-03-05 | 2015-12-24 | アッヴィ・インコーポレイテッド | IL-17 binding protein |
SI3260136T1 (en) | 2009-03-17 | 2021-05-31 | Theraclone Sciences, Inc. | Human immunodeficiency virus (hiv) -neutralizing antibodies |
TW201544123A (en) | 2009-03-20 | 2015-12-01 | Genentech Inc | Anti-HER antibodies |
EP2679600A1 (en) * | 2009-03-25 | 2014-01-01 | Genentech, Inc. | Anti-FGFR3 antibodies and methods using same |
UA108199C2 (en) | 2009-03-25 | 2015-04-10 | ANTIBODY AGAINST α5β1 AND ITS APPLICATION | |
US20120039920A1 (en) | 2009-03-31 | 2012-02-16 | Rasmussen Jerald K | Hydrophobic monomers, hydrophobically-derivatized supports, and methods of making and using the same |
JP5795306B2 (en) | 2009-04-01 | 2015-10-14 | ジェネンテック, インコーポレイテッド | Treatment of insulin resistance disease |
WO2010120561A1 (en) | 2009-04-01 | 2010-10-21 | Genentech, Inc. | Anti-fcrh5 antibodies and immunoconjugates and methods of use |
RU2598248C2 (en) | 2009-04-02 | 2016-09-20 | Роше Гликарт Аг | Polyspecific antibodies containing antibody of full length and one-chain fragments fab |
US20100297127A1 (en) | 2009-04-08 | 2010-11-25 | Ghilardi Nico P | Use of il-27 antagonists to treat lupus |
WO2010115932A1 (en) | 2009-04-08 | 2010-10-14 | Novartis Ag | Combination for the treatment of bone loss |
AU2010239131A1 (en) | 2009-04-21 | 2011-11-17 | Genetic Technologies Limited | Methods for obtaining fetal genetic material |
CA2759506A1 (en) * | 2009-04-23 | 2010-10-28 | Theraclone Sciences, Inc. | Granulocyte-macrophage colony-stimulating factor (gm-csf) neutralizing antibodies |
US9062116B2 (en) | 2009-04-23 | 2015-06-23 | Infinity Pharmaceuticals, Inc. | Anti-fatty acid amide hydrolase-2 antibodies and uses thereof |
JP2012525149A (en) * | 2009-04-27 | 2012-10-22 | オンコメッド ファーマシューティカルズ インコーポレイテッド | Method for making heteromultimeric molecules |
US8680055B2 (en) | 2009-06-03 | 2014-03-25 | University Of Southern California | Methods for decreasing steroidogenesis in prostate cancer cells |
WO2011005715A1 (en) | 2009-07-07 | 2011-01-13 | Genentech, Inc. | Diagnosis and treatment of autoimmune demyelinating diseases |
EP2456890A1 (en) | 2009-07-20 | 2012-05-30 | Genentech, Inc. | Gene expression markers for crohn's disease |
JP5665866B2 (en) | 2009-07-24 | 2015-02-04 | アコーニ バイオシステムズAkonni Biosystems | Flow cell device |
TW201106972A (en) | 2009-07-27 | 2011-03-01 | Genentech Inc | Combination treatments |
UY32808A (en) * | 2009-07-29 | 2011-02-28 | Abbott Lab | IMMUNOGLOBULINS AS A DUAL VARIABLE DOMAIN AND USES OF THE SAME |
WO2011014750A1 (en) | 2009-07-31 | 2011-02-03 | Genentech, Inc. | Inhibition of tumor metastasis using bv8- or g-csf-antagonists |
HUE038451T2 (en) | 2009-08-06 | 2018-10-29 | Hoffmann La Roche | Method to improve virus removal in protein purification |
WO2011018421A1 (en) | 2009-08-10 | 2011-02-17 | Morphosys Ag | Novel screening strategies for the identification of binders |
WO2011019679A1 (en) | 2009-08-11 | 2011-02-17 | Allergan, Inc. | Ccr2 inhibitors for treating conditions of the eye |
RU2639288C2 (en) | 2009-08-11 | 2017-12-20 | Дженентек, Инк. | Proteins production in cultural media without glutamine |
WO2011022264A1 (en) | 2009-08-15 | 2011-02-24 | Genentech, Inc. | Anti-angiogenesis therapy for the treatment of previously treated breast cancer |
CN105131112A (en) | 2009-08-29 | 2015-12-09 | Abbvie公司 | Therapeutic dll4 binding proteins |
EP2473524A4 (en) | 2009-09-01 | 2013-05-22 | Abbott Lab | Dual variable domain immunoglobulins and uses thereof |
ES2599076T3 (en) | 2009-09-02 | 2017-01-31 | Genentech, Inc. | Smoothened mutant and methods of use thereof |
SG179196A1 (en) | 2009-09-16 | 2012-04-27 | Genentech Inc | Coiled coil and/or tether containing protein complexes and uses thereof |
MX2012002909A (en) | 2009-09-17 | 2012-04-19 | Hoffmann La Roche | Methods and compositions for diagnostics use in cancer patients. |
US8470552B2 (en) * | 2009-10-12 | 2013-06-25 | Keck Graduate Institute | Strategy to reduce lactic acid production and control PH in animal cell culture |
EP2488658A4 (en) | 2009-10-15 | 2013-06-19 | Abbvie Inc | Dual variable domain immunoglobulins and uses thereof |
JP5965318B2 (en) | 2009-10-16 | 2016-08-03 | オンコメッド ファーマシューティカルズ インコーポレイテッド | Therapeutic combinations of DLL4 antagonists and antihypertensive agents and methods of treatment therewith |
AU2010310746B2 (en) | 2009-10-20 | 2015-07-23 | Nestec S.A. | Proximity-mediated assays for detecting oncogenic fusion proteins |
US8435511B2 (en) | 2009-10-22 | 2013-05-07 | Genentech, Inc. | Anti-hepsin antibodies and methods using same |
KR20120105446A (en) | 2009-10-22 | 2012-09-25 | 제넨테크, 인크. | Methods and compositions for modulating hepsin activation of macrophage-stimulating protein |
WO2011056497A1 (en) | 2009-10-26 | 2011-05-12 | Genentech, Inc. | Activin receptor type iib compositions and methods of use |
WO2011056502A1 (en) | 2009-10-26 | 2011-05-12 | Genentech, Inc. | Bone morphogenetic protein receptor type ii compositions and methods of use |
WO2011056494A1 (en) | 2009-10-26 | 2011-05-12 | Genentech, Inc. | Activin receptor-like kinase-1 antagonist and vegfr3 antagonist combinations |
UY32979A (en) * | 2009-10-28 | 2011-02-28 | Abbott Lab | IMMUNOGLOBULINS WITH DUAL VARIABLE DOMAIN AND USES OF THE SAME |
MX2012005117A (en) | 2009-10-30 | 2012-06-14 | Abbott Lab | Sorf constructs and multiple gene expression. |
WO2011051466A1 (en) | 2009-11-02 | 2011-05-05 | Novartis Ag | Anti-idiotypic fibronectin-based binding molecules and uses thereof |
CA2780221A1 (en) | 2009-11-04 | 2011-05-12 | Fabrus Llc | Methods for affinity maturation-based antibody optimization |
KR101968766B1 (en) | 2009-11-05 | 2019-04-12 | 제넨테크, 인크. | Methods and composition for secretion of heterologous polypeptides |
AU2010324686B2 (en) | 2009-11-30 | 2016-05-19 | Genentech, Inc. | Antibodies for treating and diagnosing tumors expressing SLC34A2 (TAT211 = SEQID2 ) |
US11377485B2 (en) | 2009-12-02 | 2022-07-05 | Academia Sinica | Methods for modifying human antibodies by glycan engineering |
US10087236B2 (en) | 2009-12-02 | 2018-10-02 | Academia Sinica | Methods for modifying human antibodies by glycan engineering |
CA2781682A1 (en) | 2009-12-04 | 2011-06-09 | Genentech, Inc. | Multispecific antibodies, antibody analogs, compositions, and methods |
EP2509626B1 (en) | 2009-12-11 | 2016-02-10 | F.Hoffmann-La Roche Ag | Anti-vegf-c antibodies and methods using same |
WO2011084750A1 (en) | 2009-12-21 | 2011-07-14 | Genentech, Inc. | Antibody formulation |
GB0922553D0 (en) | 2009-12-23 | 2010-02-10 | Fusion Antibodies Ltd | Prognostic marker |
CA2784385A1 (en) | 2009-12-23 | 2011-06-30 | Genentech, Inc. | Anti-bv8 antibodies and uses thereof |
WO2011080796A1 (en) | 2009-12-28 | 2011-07-07 | Oncotherapy Science, Inc. | Anti-cdh3 antibodies and uses thereof |
AU2011205316B2 (en) | 2010-01-13 | 2015-05-28 | Oncomed Pharmaceuticals, Inc. | Notch1 binding agents and methods of use thereof |
ES2551871T3 (en) | 2010-01-29 | 2015-11-24 | Morphosys Ag | Combinatorial rodent antibody libraries |
NZ601743A (en) | 2010-02-12 | 2014-11-28 | Oncomed Pharm Inc | Methods for identifying and isolating cells expressing a polypeptide |
EP3696194A1 (en) | 2010-02-23 | 2020-08-19 | F. Hoffmann-La Roche AG | Anti-angiogenesis therapy for the treatment of ovarian cancer |
US8877897B2 (en) | 2010-02-23 | 2014-11-04 | Genentech, Inc. | Compositions and methods for the diagnosis and treatment of tumor |
NZ724971A (en) | 2010-02-24 | 2019-06-28 | Immunogen Inc | Folate receptor 1 antibodies and immunoconjugates and uses thereof |
MY160628A (en) | 2010-03-02 | 2017-03-15 | Abbvie Inc | Therapeutic DLL4 Binding Proteins |
ES2748347T3 (en) | 2010-03-12 | 2020-03-16 | Debiopharm Int Sa | CD37 binding molecules and immunoconjugates thereof |
KR20180000342A (en) | 2010-03-22 | 2018-01-02 | 제넨테크, 인크. | Compositions and methods useful for stabilizing protein-containing formulations |
AR080793A1 (en) | 2010-03-26 | 2012-05-09 | Roche Glycart Ag | BISPECIFIC ANTIBODIES |
WO2011130332A1 (en) | 2010-04-12 | 2011-10-20 | Academia Sinica | Glycan arrays for high throughput screening of viruses |
BR112012026098A2 (en) | 2010-04-16 | 2016-11-22 | Novartis Ag | methods and compositions for improving implant osseointegration. |
WO2011133931A1 (en) | 2010-04-22 | 2011-10-27 | Genentech, Inc. | Use of il-27 antagonists for treating inflammatory bowel disease |
CA2796633C (en) | 2010-04-23 | 2020-10-27 | Genentech, Inc. | Production of heteromultimeric proteins |
BR112012028010A2 (en) | 2010-05-03 | 2017-09-26 | Genentech Inc | isolated antibody, cell, isolated nucleic acid, method of identifying a first antibody that binds to a tat425 antigenic epitope attached to an antibody, methods of inhibiting cell growth, therapeutic treatment of determining the presence of a tat425 protein and diagnosing the presence of a tumor in a mammal |
BR112012027828A2 (en) | 2010-05-03 | 2016-08-09 | Genentech Inc | matter composition, article of manufacture and method of reducing the viscosity of a protein containing formulation and preparing an aqueous protein containing formulation |
KR20130066631A (en) | 2010-05-06 | 2013-06-20 | 노파르티스 아게 | Compositions and methods of use for therapeutic low density lipoprotein - related protein 6 (lrp6) multivalent antibodies |
EP4234698A3 (en) | 2010-05-06 | 2023-11-08 | Novartis AG | Compositions and methods of use for therapeutic low density lipoprotein-related protein 6 (lrp6) antibodies |
CN103068378B (en) | 2010-05-10 | 2016-07-06 | 中央研究院 | Zanamivir phosphonate ester congener with anti-influenza activity and preparation method thereof |
PE20130205A1 (en) | 2010-05-14 | 2013-03-24 | Abbvie Inc | IL-1 BINDING PROTEINS |
WO2011146568A1 (en) | 2010-05-19 | 2011-11-24 | Genentech, Inc. | Predicting response to a her inhibitor |
SG185737A1 (en) | 2010-05-25 | 2013-01-30 | Genentech Inc | Methods of purifying polypeptides |
WO2011153243A2 (en) | 2010-06-02 | 2011-12-08 | Genentech, Inc. | Anti-angiogenesis therapy for treating gastric cancer |
RU2613886C2 (en) | 2010-06-03 | 2017-03-21 | Дженентек, Инк. | Antibodies and immunoconjugates rendered by immuno-positron emission tomography, methods of application |
WO2011156369A2 (en) * | 2010-06-07 | 2011-12-15 | Dr. Reddy's Laboratories Ltd. | Purification of modified cytokines |
US20110311527A1 (en) | 2010-06-16 | 2011-12-22 | Allergan, Inc. | IL23p19 ANTIBODY INHIBITOR FOR TREATING OCULAR AND OTHER CONDITIONS |
SI3586826T1 (en) | 2010-06-24 | 2021-09-30 | F. Hoffmann-La Roche Ag | Compositions and methods for stabilizing protein-containing formulations |
WO2012006500A2 (en) | 2010-07-08 | 2012-01-12 | Abbott Laboratories | Monoclonal antibodies against hepatitis c virus core protein |
UY33492A (en) | 2010-07-09 | 2012-01-31 | Abbott Lab | IMMUNOGLOBULINS WITH DUAL VARIABLE DOMAIN AND USES OF THE SAME |
US20130177500A1 (en) | 2010-07-23 | 2013-07-11 | Trustee Of Boston University | Anti-despr inhibitors as therapeutics for inhibition of pathological angiogenesis and tumor cell invasiveness and for molecular imaging and targeted delivery |
EP3252072A3 (en) | 2010-08-03 | 2018-03-14 | AbbVie Inc. | Dual variable domain immunoglobulins and uses thereof |
WO2012019024A2 (en) | 2010-08-04 | 2012-02-09 | Immunogen, Inc. | Her3-binding molecules and immunoconjugates thereof |
EP2603237A4 (en) | 2010-08-12 | 2014-05-21 | Theraclone Sciences Inc | Anti-hemagglutinin antibody compositions and methods of use thereof |
EP2420250A1 (en) | 2010-08-13 | 2012-02-22 | Universitätsklinikum Münster | Anti-Syndecan-4 antibodies |
US20130177555A1 (en) | 2010-08-13 | 2013-07-11 | Medimmune Limited | Monomeric Polypeptides Comprising Variant FC Regions And Methods Of Use |
CN104474546A (en) | 2010-08-13 | 2015-04-01 | 弗·哈夫曼-拉罗切有限公司 | Antibodies to il-1beta and il-18, for treatment of disease |
WO2012022734A2 (en) | 2010-08-16 | 2012-02-23 | Medimmune Limited | Anti-icam-1 antibodies and methods of use |
BR112013004012B1 (en) | 2010-08-20 | 2021-03-23 | Novartis Ag | ISOLATED MONOCLONAL ANTIBODY OR ANTIGEN BINDING FRAGMENT OF THE SAME TO THE HER3 RECEPTOR, ITS USE AND PHARMACEUTICAL COMPOSITION |
WO2012024663A1 (en) * | 2010-08-20 | 2012-02-23 | Ge Healthcare Limited | Quality control devices and methods for radiopharmaceuticals |
WO2012025530A1 (en) | 2010-08-24 | 2012-03-01 | F. Hoffmann-La Roche Ag | Bispecific antibodies comprising a disulfide stabilized - fv fragment |
KR20130139884A (en) | 2010-08-26 | 2013-12-23 | 애브비 인코포레이티드 | Dual variable domain immunoglobulins and uses thereof |
CA3201524A1 (en) | 2010-08-31 | 2012-03-08 | Theraclone Sciences, Inc. | Human immunodeficiency virus (hiv)-neutralizing antibodies |
WO2012030512A1 (en) * | 2010-09-03 | 2012-03-08 | Percivia Llc. | Flow-through protein purification process |
WO2012032043A1 (en) | 2010-09-07 | 2012-03-15 | Areva Med Llc | 212 pb imaging |
CN103201293B (en) | 2010-09-08 | 2016-04-27 | 哈洛齐梅公司 | The method of assessment and qualification or development condition active therapeutic protein |
US8551479B2 (en) | 2010-09-10 | 2013-10-08 | Oncomed Pharmaceuticals, Inc. | Methods for treating melanoma |
EP2619578B1 (en) * | 2010-09-24 | 2016-12-14 | Full Spectrum Genetics Inc. | Method of analyzing binding interactions |
DK2625197T3 (en) | 2010-10-05 | 2016-10-03 | Genentech Inc | Smoothened MUTANT AND METHODS OF USING THE SAME |
WO2012061129A1 (en) | 2010-10-25 | 2012-05-10 | Genentech, Inc | Treatment of gastrointestinal inflammation and psoriasis a |
WO2012071436A1 (en) | 2010-11-24 | 2012-05-31 | Genentech, Inc. | Method of treating autoimmune inflammatory disorders using il-23r loss-of-function mutants |
WO2012069466A1 (en) | 2010-11-24 | 2012-05-31 | Novartis Ag | Multispecific molecules |
WO2012075333A2 (en) | 2010-12-02 | 2012-06-07 | Prometheus Laboratories Inc. | Her2delta16 peptides |
SG191312A1 (en) | 2010-12-21 | 2013-07-31 | Abbvie Inc | Il-1 -alpha and -beta bispecific dual variable domain immunoglobulins and their use |
AU2011348256A1 (en) | 2010-12-23 | 2013-07-11 | Nestec S.A. | Drug selection for malignant cancer therapy using antibody-based arrays |
CN103270047A (en) | 2010-12-23 | 2013-08-28 | 因特塞尔奥地利股份公司 | Oprf/i agents and their use in hospitalized and other patients |
JP5766296B2 (en) | 2010-12-23 | 2015-08-19 | エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft | Polypeptide-polynucleotide complexes and their use in targeted delivery of effector components |
WO2012092539A2 (en) | 2010-12-31 | 2012-07-05 | Takeda Pharmaceutical Company Limited | Antibodies to dll4 and uses thereof |
US20150018408A1 (en) | 2013-07-10 | 2015-01-15 | The Regents Of The University Of Michigan | Therapeutic antibodies and uses thereof |
CN103547288B (en) | 2011-01-10 | 2016-03-16 | 密执安大学评议会 | Stem cell factor inhibitor |
KR101913448B1 (en) | 2011-02-04 | 2018-10-30 | 제넨테크, 인크. | Fc VARIANTS AND METHODS FOR THEIR PRODUCTION |
US10689447B2 (en) | 2011-02-04 | 2020-06-23 | Genentech, Inc. | Fc variants and methods for their production |
WO2012112489A2 (en) | 2011-02-14 | 2012-08-23 | Theraclone Sciences, Inc. | Compositions and methods for the therapy and diagnosis of influenza |
WO2012119989A2 (en) | 2011-03-04 | 2012-09-13 | Oryzon Genomics, S.A. | Methods and antibodies for the diagnosis and treatment of cancer |
US20140099264A1 (en) | 2011-03-07 | 2014-04-10 | F. Hoffman-La Roche Ag | Means and methods for in vivo testing of therapeutic antibodies |
JP6385060B2 (en) | 2011-03-07 | 2018-09-05 | エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト | In vivo selection of therapeutically active antibodies |
KR20190107761A (en) | 2011-03-09 | 2019-09-20 | 셀 시그널링 테크놀러지, 인크. | Methods and reagents for creating monoclonal antibodies |
WO2012125614A1 (en) | 2011-03-15 | 2012-09-20 | Theraclone Sciences, Inc. | Compositions and methods for the therapy and diagnosis of influenza |
BR112013024521A2 (en) | 2011-03-25 | 2019-09-24 | Genentech Inc | protein purification methods |
EP3412309A1 (en) | 2011-03-31 | 2018-12-12 | F. Hoffmann-La Roche AG | Methods of administering beta7 integrin antagonists |
AP2013007180A0 (en) | 2011-04-25 | 2013-10-31 | Advanced Bioscience Lab Inc | Truncated HIV envelope proteins (ENV), methods andcompositions related thereto |
US20140056912A1 (en) | 2011-04-29 | 2014-02-27 | Novartis Ag | Methods of treating squamous cell carcinoma |
US20140141458A1 (en) | 2011-05-12 | 2014-05-22 | The Johns Hopkins University | Assay reagents for a neurogranin diagnostic kit |
JP6323718B2 (en) | 2011-05-17 | 2018-05-16 | ザ ロックフェラー ユニバーシティー | Antibodies that detoxify human immunodeficiency virus and methods of use thereof. |
WO2012172495A1 (en) | 2011-06-14 | 2012-12-20 | Novartis Ag | Compositions and methods for antibodies targeting tem8 |
EP2540828A1 (en) | 2011-06-30 | 2013-01-02 | Gene Signal International SA | Composition comprising inhibitors of IRS-1 and of VEGF |
EP2726612B1 (en) | 2011-06-30 | 2019-03-06 | Gene Signal International SA | Composition comprising inhibitors of irs-1 and of vegf |
JP2013040160A (en) | 2011-07-01 | 2013-02-28 | Genentech Inc | Use of anti-cd83 agonist antibody for treating autoimmune disease |
PT2731677T (en) | 2011-07-11 | 2018-07-27 | Glenmark Pharmaceuticals Sa | Antibodies that bind to ox40 and their uses |
WO2013015821A1 (en) | 2011-07-22 | 2013-01-31 | The Research Foundation Of State University Of New York | Antibodies to the b12-transcobalamin receptor |
US20130022551A1 (en) | 2011-07-22 | 2013-01-24 | Trustees Of Boston University | DEspR ANTAGONISTS AND AGONISTS AS THERAPEUTICS |
US9120858B2 (en) | 2011-07-22 | 2015-09-01 | The Research Foundation Of State University Of New York | Antibodies to the B12-transcobalamin receptor |
WO2013016468A2 (en) | 2011-07-25 | 2013-01-31 | California Institute Of Technology | Compositions and methods for improving potency and breadth or hiv antibodies |
US9493549B2 (en) | 2011-07-25 | 2016-11-15 | The Rockefeller University | Antibodies directed toward the HIV-1 GP120 CD4 binding site with increased potency and breadth |
CN103842030B (en) | 2011-08-01 | 2018-07-31 | 霍夫曼-拉罗奇有限公司 | Use the method for PD-1 axis binding antagonists and mek inhibitor treating cancer |
KR20140068877A (en) | 2011-08-17 | 2014-06-09 | 제넨테크, 인크. | Inhibition of angiogenesis in refractory tumors |
US8822651B2 (en) | 2011-08-30 | 2014-09-02 | Theraclone Sciences, Inc. | Human rhinovirus (HRV) antibodies |
EP2751562B1 (en) | 2011-09-02 | 2015-09-16 | Nestec S.A. | Profiling of signal pathway proteins to determine therapeutic efficacy |
EP3485903B1 (en) | 2011-09-23 | 2022-11-16 | Mereo BioPharma 5, Inc. | Vegf/dll4 binding agents and uses thereof |
US9575073B2 (en) | 2011-10-10 | 2017-02-21 | Rutgers, The State University Of New Jersey | Detection of high-risk intraductal papillary mucinous neoplasm and pancreatic adenocarcinoma |
PL2766397T3 (en) | 2011-10-11 | 2018-10-31 | F.Hoffmann-La Roche Ag | Improved assembly of bispecific antibodies |
WO2013054320A1 (en) | 2011-10-11 | 2013-04-18 | Tel Hashomer Medical Research Infrastructure And Services Ltd. | Antibodies to carcinoembryonic antigen-related cell adhesion molecule (ceacam) |
EP2766037A4 (en) | 2011-10-12 | 2015-08-05 | Scripps Research Inst | An hiv-1 gp120 mini v3 loop and uses thereof |
EP2581388A1 (en) | 2011-10-14 | 2013-04-17 | Centre National de la Recherche Scientifique (CNRS) | Anti-sPLA2-V antibodies and uses thereof |
ES2769786T3 (en) | 2011-10-14 | 2020-06-29 | Recordati Ag | Antibodies and methods for diseases related to the Wnt pathway |
UY34411A (en) | 2011-10-24 | 2013-05-31 | Abbvie Inc | IMMUNO LINKERS AGAINST SCLEROSTINE |
AR088514A1 (en) | 2011-10-24 | 2014-06-18 | Abbvie Inc | BISPECIFIC IMMUNOLIGANTS DIRECTED AGAINST TNF |
WO2013067301A1 (en) | 2011-11-02 | 2013-05-10 | Genentech, Inc. | Overload and elute chromatography |
DK2797957T3 (en) | 2011-11-23 | 2019-09-23 | Medimmune Llc | BINDING MOLECULES SPECIFIC TO HER3 AND APPLICATIONS THEREOF |
DK2785375T3 (en) | 2011-11-28 | 2020-10-12 | Merck Patent Gmbh | ANTI-PD-L1 ANTIBODIES AND USES THEREOF |
WO2013082511A1 (en) | 2011-12-02 | 2013-06-06 | Genentech, Inc. | Methods for overcoming tumor resistance to vegf antagonists |
JP2015500829A (en) | 2011-12-05 | 2015-01-08 | ノバルティス アーゲー | HER3 antibody against domain II of epidermal growth factor receptor 3 (HER3) |
WO2013084147A2 (en) | 2011-12-05 | 2013-06-13 | Novartis Ag | Antibodies for epidermal growth factor receptor 3 (her3) |
EP2602265A1 (en) | 2011-12-07 | 2013-06-12 | Centre National de la Recherche Scientifique (CNRS) | Antibodies anti-sPLA2-X and uses thereof |
CN104284680A (en) | 2011-12-15 | 2015-01-14 | 芝加哥大学 | Methods and compositions for cancer therapy using mutant light molecules with increased affinity to receptors |
ES2728278T3 (en) | 2011-12-21 | 2019-10-23 | Novartis Ag | Compositions comprising antibodies directed to factor P and C5 |
MY172426A (en) | 2011-12-22 | 2019-11-25 | Genentech Inc | Ion exchange membrane chromatography |
WO2013091903A1 (en) | 2011-12-22 | 2013-06-27 | Novo Nordisk A/S | Anti-crac channel antibodies |
WO2013101771A2 (en) | 2011-12-30 | 2013-07-04 | Genentech, Inc. | Compositions and method for treating autoimmune diseases |
CN104159920A (en) | 2011-12-30 | 2014-11-19 | 艾伯维公司 | Dual specific binding proteins directed against il-13 and/or il-17 |
JP2015509091A (en) | 2012-01-09 | 2015-03-26 | ザ スクリプス リサーチ インスティテュート | Humanized antibody |
US10774132B2 (en) | 2012-01-09 | 2020-09-15 | The Scripps Research Instittue | Ultralong complementarity determining regions and uses thereof |
TW201334789A (en) | 2012-01-31 | 2013-09-01 | Genentech Inc | Anti-IgE antibodies and methods using same |
KR20140127854A (en) | 2012-02-10 | 2014-11-04 | 제넨테크, 인크. | Single-chain antibodies and other heteromultimers |
US20140170159A9 (en) | 2012-03-08 | 2014-06-19 | Ge Wei | Conditionally active anti-epidermal growth factor receptor antibodies and methods of use thereof |
EP2641916A1 (en) | 2012-03-23 | 2013-09-25 | Centre National de la Recherche Scientifique (C.N.R.S) | Novel antibodies anti-sPLA2-IIA and uses thereof |
RU2014136886A (en) | 2012-03-27 | 2016-05-20 | Дженентек, Инк. | DIAGNOSTIC AND TREATMENT TYPES RELATED TO HER3 INHIBITORS |
US20150050240A1 (en) | 2012-03-27 | 2015-02-19 | Novartis Ag | Treatment of fibrosis |
EP3492095A1 (en) | 2012-04-01 | 2019-06-05 | Technion Research & Development Foundation Limited | Extracellular matrix metalloproteinase inducer (emmprin) peptides and binding antibodies |
US10130714B2 (en) | 2012-04-14 | 2018-11-20 | Academia Sinica | Enhanced anti-influenza agents conjugated with anti-inflammatory activity |
SG10201603055WA (en) | 2012-05-31 | 2016-05-30 | Genentech Inc | Methods Of Treating Cancer Using PD-L1 Axis Binding Antagonists And VEGF Antagonists |
US20150104468A1 (en) | 2012-06-04 | 2015-04-16 | Irm Llc | Site-specific labeling methods and molecules produced thereby |
AP2014008145A0 (en) | 2012-06-08 | 2014-12-31 | Glenmark Pharmaceuticals Sa | Humanized anti-trkA antibodies with animo acid substitutions |
WO2013192589A1 (en) | 2012-06-21 | 2013-12-27 | California Institute Of Technology | Antibodies targeting hiv escape mutants |
JOP20130186B1 (en) | 2012-06-22 | 2021-08-17 | Takeda Vaccines Montana Inc | Purification of virus like particles |
BR112014028368A2 (en) | 2012-06-27 | 2017-11-14 | Hoffmann La Roche | method of producing antibody fc region conjugate, antibody fc region conjugate and pharmaceutical formulation |
CA2871880A1 (en) | 2012-06-27 | 2014-01-03 | F. Hoffmann-La Roche Ag | Method for selection and production of tailor-made highly selective and multi-specific targeting entities containing at least two different binding entities and uses thereof |
WO2014011955A2 (en) | 2012-07-12 | 2014-01-16 | Abbvie, Inc. | Il-1 binding proteins |
WO2014018375A1 (en) | 2012-07-23 | 2014-01-30 | Xenon Pharmaceuticals Inc. | Cyp8b1 and uses thereof in therapeutic and diagnostic methods |
JP2015525781A (en) | 2012-07-31 | 2015-09-07 | ザ ブリガム アンド ウィメンズ ホスピタル インコーポレイテッドThe Brigham and Women’s Hospital, Inc. | Modulating the immune response |
US9297806B2 (en) | 2012-08-01 | 2016-03-29 | The Johns Hopkins University | 5-hydroxymethylcytosine in human cancer |
FR2994390B1 (en) | 2012-08-10 | 2014-08-15 | Adocia | METHOD FOR LOWERING THE VISCOSITY OF HIGH CONCENTRATION PROTEIN SOLUTIONS |
CA2880701A1 (en) | 2012-08-18 | 2014-02-27 | Academia Sinica | Cell-permeable probes for identification and imaging of sialidases |
US20140057303A1 (en) | 2012-08-21 | 2014-02-27 | Janssen Pharmaceutica Nv | Antibodies to Olanzapine Haptens and Use Thereof |
WO2014031762A1 (en) | 2012-08-21 | 2014-02-27 | Academia Sinica | Benzocyclooctyne compounds and uses thereof |
CN106928369B (en) | 2012-08-21 | 2021-04-02 | 奥索临床诊断有限公司 | Antibodies to quetiapine and uses thereof |
CN104755631B (en) | 2012-08-21 | 2017-09-05 | 詹森药业有限公司 | Antibody of Aripiprazole and application thereof |
AU2013305938B2 (en) | 2012-08-21 | 2017-08-17 | Saladax Biomedical Inc. | Antibodies to paliperidone haptens and use thereof |
CN104755928B (en) | 2012-08-21 | 2017-05-10 | 詹森药业有限公司 | Antibodies to olanzapine and use thereof |
PT2888234T (en) | 2012-08-21 | 2018-02-22 | Janssen Pharmaceutica Nv | Haptens of aripiprazole and their use in immunoassays |
JP6374387B2 (en) | 2012-08-21 | 2018-08-15 | ヤンセン ファーマシューティカ エヌ.ベー. | Antibody to risperidone hapten and use thereof |
TR201816416T4 (en) | 2012-08-21 | 2018-11-21 | Janssen Pharmaceutica Nv | Antibodies to risperidone and their use. |
CN110054694B (en) | 2012-08-21 | 2024-02-20 | 詹森药业有限公司 | Antibodies to aripiprazole hapten and uses thereof |
WO2014031665A1 (en) | 2012-08-21 | 2014-02-27 | Ortho-Clinical Diagnostics, Inc | Antibodies to quetiapine haptens and use thereof |
CN108640996A (en) | 2012-08-21 | 2018-10-12 | 詹森药业有限公司 | Antibody of Paliperidone and application thereof |
KR20240005129A (en) | 2012-08-31 | 2024-01-11 | 이뮤노젠 아이엔씨 | Diagnostic assays and kits for detection of folate receptor 1 |
WO2014040025A2 (en) | 2012-09-10 | 2014-03-13 | International Aids Vaccine Initiative | Immunogens of hiv-1 broadly neutralizing antibodies, methods of generation and uses thereof |
CA2888659A1 (en) | 2012-10-18 | 2014-04-24 | Rockefeller University (The) | Broadly-neutralizing anti-hiv antibodies |
JP6371294B2 (en) | 2012-10-31 | 2018-08-08 | オンコメッド ファーマシューティカルズ インコーポレイテッド | Methods and monitoring of treatment with DLL4 antagonists |
KR20180008921A (en) | 2012-11-01 | 2018-01-24 | 애브비 인코포레이티드 | Anti-vegf/dll4 dual variable domain immunoglobulins and uses thereof |
BR112015011011A2 (en) | 2012-11-15 | 2019-12-17 | Genentech Inc | ion-strength ion-gradient ion exchange chromatography |
WO2014084859A1 (en) | 2012-11-30 | 2014-06-05 | Novartis Ag | Molecules and methods for modulating tmem16a activities |
EP3851454A1 (en) | 2012-12-05 | 2021-07-21 | Novartis AG | Compositions and methods for antibodies targeting epo |
JP2016502850A (en) | 2012-12-18 | 2016-02-01 | ノバルティス アーゲー | Compositions and methods using peptide tags that bind to hyaluronan |
US9458244B2 (en) | 2012-12-28 | 2016-10-04 | Abbvie Inc. | Single chain multivalent binding protein compositions and methods |
EP2938637A2 (en) | 2012-12-28 | 2015-11-04 | AbbVie Inc. | Multivalent binding protein compositions |
CN105102067B (en) | 2013-01-02 | 2020-03-03 | 艾科诺斯科技股份有限公司 | Antibodies that bind TL1A and uses thereof |
EP2948177A1 (en) | 2013-01-22 | 2015-12-02 | AbbVie Inc. | Methods for optimizing domain stability of binding proteins |
WO2014116846A2 (en) | 2013-01-23 | 2014-07-31 | Abbvie, Inc. | Methods and compositions for modulating an immune response |
WO2014118705A1 (en) | 2013-01-31 | 2014-08-07 | Novartis Ag | Methods of treating chronic kidney disease-mineral and bone disorder using sclerostin antagonists |
WO2014120975A1 (en) | 2013-02-01 | 2014-08-07 | California Institute Of Technology | Antibody-mediated immunocontraception |
KR102447350B1 (en) | 2013-02-08 | 2022-09-23 | 노파르티스 아게 | Specific sites for modifying antibodies to make immunoconjugates |
WO2014124258A2 (en) | 2013-02-08 | 2014-08-14 | Irm Llc | Specific sites for modifying antibodies to make immunoconjugates |
RU2015140573A (en) | 2013-02-25 | 2017-03-30 | Дженентек, Инк. | METHODS AND COMPOSITIONS FOR DETECTION AND TREATMENT OF DRUG-RESISTANT MUTANT RESISTANT TO MEDICINES |
US9809645B2 (en) | 2013-03-12 | 2017-11-07 | Zenyaku Kogyo Kabushikikaisha | Anti-Staphylococcus antibody, method for manufacturing same, and usage of same |
US10653779B2 (en) | 2013-03-13 | 2020-05-19 | Genentech, Inc. | Formulations with reduced oxidation |
SG10201705525VA (en) | 2013-03-13 | 2017-08-30 | Genentech Inc | Formulations with reduced oxidation |
CN105209058A (en) | 2013-03-13 | 2015-12-30 | 豪夫迈·罗氏有限公司 | Formulations with reduced oxidation |
EP3744345B1 (en) | 2013-03-13 | 2022-02-09 | F. Hoffmann-La Roche AG | Antibody formulations |
AR095398A1 (en) | 2013-03-13 | 2015-10-14 | Genentech Inc | FORMULATIONS WITH REDUCED OXIDATION |
EP2970468B1 (en) | 2013-03-13 | 2021-07-07 | Novartis AG | Notch2 binding molecules for treating respiratory diseases |
US9498532B2 (en) | 2013-03-13 | 2016-11-22 | Novartis Ag | Antibody drug conjugates |
MX2015012825A (en) | 2013-03-14 | 2016-06-10 | Abbott Lab | Hcv core lipid binding domain monoclonal antibodies. |
EP3611189A1 (en) | 2013-03-14 | 2020-02-19 | Novartis AG | Antibodies against notch 3 |
BR112015023355A8 (en) | 2013-03-14 | 2018-01-30 | Abbott Lab | hcv ns3 recombinant antigens and mutants thereof for enhanced antibody detection. |
CA2906421C (en) | 2013-03-14 | 2022-08-16 | George J. Dawson | Hcv antigen-antibody combination assay and methods and compositions for use therein |
US9789203B2 (en) | 2013-03-15 | 2017-10-17 | Novartis Ag | cKIT antibody drug conjugates |
JP6591395B2 (en) | 2013-03-15 | 2019-10-16 | ジェネンテック, インコーポレイテッド | Cell culture compositions containing antioxidants and methods for polypeptide production |
EP2968544A4 (en) | 2013-03-15 | 2016-10-12 | Hoffmann La Roche | Cell culture media and methods of antibody production |
CN105324396A (en) | 2013-03-15 | 2016-02-10 | 艾伯维公司 | Dual specific binding proteins directed against il-1 beta and il-17 |
JP6592426B2 (en) * | 2013-03-15 | 2019-10-16 | バイオジェン・エムエイ・インコーポレイテッドBiogen MA Inc. | Protein purification using hydrophobic interaction chromatography under salt-free conditions |
US20140283157A1 (en) | 2013-03-15 | 2014-09-18 | Diadexus, Inc. | Lipoprotein-associated phospholipase a2 antibody compositions and methods of use |
EP3495814A3 (en) | 2013-03-27 | 2019-07-17 | F. Hoffmann-La Roche AG | Use of biomarkers for assessing treatment of gastrointestinal inflammatory disorders with beta7 integrin antagonists |
US20160053023A1 (en) | 2013-04-09 | 2016-02-25 | Annexon, Inc. | Methods of treatment for neuromyelitis optica |
US9914770B2 (en) | 2013-04-30 | 2018-03-13 | Intas Pharmaceuticals Ltd | Cloning, expression and purification method for the preparation of ranibizumab |
MX367046B (en) | 2013-05-24 | 2019-08-02 | Soc Des Produits Nestle S A Star | Pathway specific markers for diagnosing irritable bowel syndrome. |
WO2014200767A1 (en) | 2013-06-12 | 2014-12-18 | The General Hospital Corporation | Methods, kits, and systems for multiplexed detection of target molecules and uses thereof |
AR096601A1 (en) | 2013-06-21 | 2016-01-20 | Novartis Ag | ANTIBODIES OF LEXINED OXIDATED LDL RECEIVER 1 AND METHODS OF USE |
UY35620A (en) | 2013-06-21 | 2015-01-30 | Novartis Ag | ANTIBODIES OF LEXINED OXIDATED LDL RECEIVER 1 AND METHODS OF USE |
TWI596107B (en) | 2013-06-25 | 2017-08-21 | 卡地拉保健有限公司 | Novel purification process for monoclonal antibodies |
WO2014210397A1 (en) | 2013-06-26 | 2014-12-31 | Academia Sinica | Rm2 antigens and use thereof |
US9981030B2 (en) | 2013-06-27 | 2018-05-29 | Academia Sinica | Glycan conjugates and use thereof |
EP3019240B1 (en) | 2013-07-09 | 2024-03-13 | Annexon, Inc. | Anti-complement factor c1q antibodies and uses thereof |
KR102251127B1 (en) | 2013-07-12 | 2021-05-11 | 제넨테크, 인크. | Elucidation of ion exchange chromatography input optimization |
US10208125B2 (en) | 2013-07-15 | 2019-02-19 | University of Pittsburgh—of the Commonwealth System of Higher Education | Anti-mucin 1 binding agents and uses thereof |
ES2819209T3 (en) | 2013-07-16 | 2021-04-15 | Hoffmann La Roche | Cancer treatment procedures using PD-1 axis binding antagonists and TIGIT inhibitors |
JP6687520B2 (en) | 2013-07-18 | 2020-04-22 | トーラス バイオサイエンシズ リミテッド ライアビリティ カンパニー | Humanized antibody with extremely long complementarity determining regions |
WO2015017146A2 (en) | 2013-07-18 | 2015-02-05 | Fabrus, Inc. | Antibodies with ultralong complementarity determining regions |
US10093978B2 (en) | 2013-08-12 | 2018-10-09 | Genentech, Inc. | Compositions for detecting complement factor H (CFH) and complement factor I (CFI) polymorphisms |
IL293871A (en) | 2013-08-30 | 2022-08-01 | Immunogen Inc | Antibodies and assays for detection of folate receptor 1 |
MX2016002798A (en) | 2013-09-05 | 2016-07-21 | Genentech Inc | Method for chromatography reuse. |
CA2923579C (en) | 2013-09-06 | 2023-09-05 | Academia Sinica | Human inkt cell activation using glycolipids with altered glycosyl groups |
EP3808338A1 (en) | 2013-09-11 | 2021-04-21 | Eagle Biologics, Inc. | Liquid protein formulations containing ionic liquids |
MX2016003256A (en) | 2013-09-12 | 2016-06-07 | Halozyme Inc | Modified anti-epidermal growth factor receptor antibodies and methods of use thereof. |
EP3044323B1 (en) | 2013-09-13 | 2022-04-06 | F. Hoffmann-La Roche AG | Methods for detecting and quantifying host cell protein in cell lines |
MX2016003202A (en) | 2013-09-13 | 2016-06-07 | Genentech Inc | Methods and compositions comprising purified recombinant polypeptides. |
MA38960A1 (en) | 2013-09-27 | 2017-10-31 | Genentech Inc | Anti-pdl1 antibody formulations |
US9243294B2 (en) | 2013-09-30 | 2016-01-26 | Hadasit Medical Research Services And Development Ltd. | Modulation of NLGn4 expression, NK cell activity in non-alcoholic fatty liver disease (NAFLD) |
WO2015050959A1 (en) | 2013-10-01 | 2015-04-09 | Yale University | Anti-kit antibodies and methods of use thereof |
CN113667012A (en) | 2013-10-02 | 2021-11-19 | 免疫医疗有限责任公司 | Neutralizing anti-influenza a antibodies and uses thereof |
JP6879739B2 (en) | 2013-11-25 | 2021-06-02 | フェイムウェイヴ リミテッド | Compositions Containing Anti-CEACAM1 and Anti-PD Antibodies for Cancer Treatment |
EP3074039A4 (en) | 2013-11-26 | 2017-10-11 | The Brigham and Women's Hospital, Inc. | Compositions and methods for modulating an immune response |
LT3079719T (en) | 2013-12-09 | 2019-12-10 | Allakos Inc | Anti-siglec-8 antibodies and methods of use thereof |
WO2015089375A1 (en) | 2013-12-13 | 2015-06-18 | The General Hospital Corporation | Soluble high molecular weight (hmw) tau species and applications thereof |
CN105899526A (en) | 2013-12-17 | 2016-08-24 | 诺华股份有限公司 | Cytotoxic peptides and conjugates thereof |
CA2934028A1 (en) | 2013-12-17 | 2015-06-25 | Genentech, Inc. | Combination therapy comprising ox40 binding agonists and pd-1 axis binding antagonists |
CN105899535A (en) | 2013-12-17 | 2016-08-24 | 豪夫迈·罗氏有限公司 | Methods of treating cancer using pd-1 axis binding antagonists and an anti-cd20 antibody |
NZ720515A (en) | 2013-12-17 | 2022-12-23 | Genentech Inc | Methods of treating cancers using pd-1 axis binding antagonists and taxanes |
MX2016006529A (en) | 2013-12-20 | 2016-08-03 | Genentech Inc | Dual specific antibodies. |
WO2015103026A2 (en) | 2014-01-03 | 2015-07-09 | The Regents Of The University Of Michigan | Treatment of neurological disorders |
EP2891657A1 (en) | 2014-01-07 | 2015-07-08 | Centre National de la Recherche Scientifique (CNRS) | Ionic liquid supported organotin reagents for the manufacturing of radiopharmaceuticals compounds |
TW201620939A (en) | 2014-01-16 | 2016-06-16 | 中央研究院 | Compositions and methods for treatment and detection of cancers |
US10150818B2 (en) | 2014-01-16 | 2018-12-11 | Academia Sinica | Compositions and methods for treatment and detection of cancers |
WO2016114819A1 (en) | 2015-01-16 | 2016-07-21 | Academia Sinica | Compositions and methods for treatment and detection of cancers |
EP2896400A1 (en) | 2014-01-17 | 2015-07-22 | Université Catholique De Louvain | Method for increasing the bioavailability of inhaled compounds |
WO2015116902A1 (en) | 2014-01-31 | 2015-08-06 | Genentech, Inc. | G-protein coupled receptors in hedgehog signaling |
DK3102197T3 (en) | 2014-02-04 | 2018-11-19 | Genentech Inc | Smoothened mutant and methods for its use |
EP3102701A1 (en) | 2014-02-07 | 2016-12-14 | Novartis AG | Impact of genetic factors on disease progression and response to anti-c5 antibody in geographic atrophy |
MX2016010623A (en) | 2014-02-19 | 2017-03-20 | Univ Tennessee Res Found | Antibody for skewing sex ratio and methods of use thereof. |
EP4014995A1 (en) | 2014-02-28 | 2022-06-22 | Allakos Inc. | Methods and compositions for treating siglec-8 associated diseases |
EA201691827A1 (en) | 2014-03-12 | 2017-01-30 | Новартис Аг | SPECIFIC PLOTS FOR MODIFICATION OF ANTIBODIES WITH THE PURPOSE OF OBTAINING IMMUNOCONJUGATES |
PL3116999T3 (en) | 2014-03-14 | 2021-12-27 | F.Hoffmann-La Roche Ag | Methods and compositions for secretion of heterologous polypeptides |
EP3119913B1 (en) | 2014-03-21 | 2021-01-06 | The Brigham and Women's Hospital, Inc. | Methods and compositions for treatment of immune-related diseases or disorders and/or therapy monitoring |
WO2015145449A2 (en) | 2014-03-27 | 2015-10-01 | Yeda Research And Development Co. Ltd. | T-cell receptor cdr3 peptides and antibodies |
JP6562942B2 (en) | 2014-03-27 | 2019-08-28 | アカデミア シニカAcademia Sinica | Reactive labeled compounds and uses thereof |
AR099856A1 (en) | 2014-03-27 | 2016-08-24 | Genentech Inc | METHODS TO DIAGNOSE AND TREAT INFLAMMED INTESTINE DISEASE |
RU2016142476A (en) | 2014-03-31 | 2018-05-07 | Дженентек, Инк. | COMBINED THERAPY, INCLUDING ANTI-ANGIOGENESIS AGENTS AND AGONISTS BINDING OX40 |
LT3128997T (en) | 2014-04-08 | 2020-10-12 | Boston Pharmaceuticals Inc. | Binding molecules specific for il-21 and uses thereof |
US10160812B2 (en) | 2014-04-11 | 2018-12-25 | Medimmune, Llc | Bispecific HER2 antibodies |
WO2015164364A2 (en) | 2014-04-25 | 2015-10-29 | The Brigham And Women's Hospital, Inc. | Methods to manipulate alpha-fetoprotein (afp) |
CA2983796A1 (en) | 2014-04-25 | 2015-10-29 | The Brigham And Women's Hospital, Inc. | Compositions and methods for treating subjects with immune-mediated diseases |
MX366359B (en) | 2014-04-27 | 2019-07-05 | Ccam Biotherapeutics Ltd | Humanized antibodies against ceacam1. |
US11427647B2 (en) | 2014-04-27 | 2022-08-30 | Famewave Ltd. | Polynucleotides encoding humanized antibodies against CEACAM1 |
WO2015171822A1 (en) | 2014-05-06 | 2015-11-12 | Genentech, Inc. | Production of heteromultimeric proteins using mammalian cells |
WO2015175375A1 (en) | 2014-05-13 | 2015-11-19 | Short Jay M | Conditionally active biological proteins |
US10118969B2 (en) | 2014-05-27 | 2018-11-06 | Academia Sinica | Compositions and methods relating to universal glycoforms for enhanced antibody efficacy |
WO2015184008A1 (en) | 2014-05-27 | 2015-12-03 | Academia Sinica | Fucosidase from bacteroides and methods using the same |
JP2017518989A (en) | 2014-05-27 | 2017-07-13 | アカデミア シニカAcademia Sinica | Anti-CD20 glycoengineered antibody group and use thereof |
AU2015267045B2 (en) | 2014-05-27 | 2021-02-25 | Academia Sinica | Anti-HER2 glycoantibodies and uses thereof |
TWI732738B (en) | 2014-05-28 | 2021-07-11 | 中央研究院 | Anti-tnf-alpha glycoantibodies and uses thereof |
CN106714830B (en) | 2014-05-30 | 2020-08-25 | 上海复宏汉霖生物技术股份有限公司 | anti-Epidermal Growth Factor Receptor (EGFR) antibodies |
US20160002326A1 (en) | 2014-06-10 | 2016-01-07 | Abbvie Inc. | Compositions and methods for treating rheumatoid arthritis |
MX2016016515A (en) | 2014-06-13 | 2017-04-27 | Novartis Ag | Auristatin derivatives and conjugates thereof. |
EP2957571B1 (en) | 2014-06-17 | 2018-08-15 | Centre National De La Recherche Scientifique (Cnrs) | Monoclonal anti-pvhl antibodies and uses thereof |
EP3160990A2 (en) | 2014-06-25 | 2017-05-03 | Novartis AG | Compositions and methods for long acting proteins |
EP3160991A2 (en) | 2014-06-25 | 2017-05-03 | Novartis AG | Compositions and methods for long acting proteins |
WO2016004055A1 (en) | 2014-07-03 | 2016-01-07 | Yale University | Dickkopf2 (Dkk2) Inhibition Suppresses Tumor Formation |
SG11201700074YA (en) | 2014-07-15 | 2017-02-27 | Genentech Inc | Compositions for treating cancer using pd-1 axis binding antagonists and mek inhibitors |
EP3539990B1 (en) | 2014-07-16 | 2021-09-08 | Dana-Farber Cancer Institute, Inc. | Her3 inhibition in low-grade serous cancers |
RU2744978C2 (en) | 2014-07-24 | 2021-03-17 | Дженентек, Инк. | Methods for conjugation of agent with thiol group in protein comprising at least one trisulfide bond |
WO2016020791A1 (en) | 2014-08-05 | 2016-02-11 | Novartis Ag | Ckit antibody drug conjugates |
EP3194437B1 (en) | 2014-08-07 | 2021-01-20 | Novartis AG | Angiopoietin-like 4 (angptl4) antibodies and methods of use |
DK3177642T3 (en) | 2014-08-07 | 2022-02-21 | Novartis Ag | ANGIOPOIETIN-LIKE 4 ANTIBODIES AND METHODS OF USING IT |
US20170240631A1 (en) | 2014-08-08 | 2017-08-24 | Alector Llc | Anti-trem2 antibodies and methods of use thereof |
KR20170040249A (en) | 2014-08-12 | 2017-04-12 | 노파르티스 아게 | Anti-cdh6 antibody drug conjugates |
US11111288B2 (en) | 2014-08-28 | 2021-09-07 | Bioatla, Inc. | Conditionally active chimeric antigen receptors for modified t-cells |
PL3186281T3 (en) | 2014-08-28 | 2019-10-31 | Halozyme Inc | Combination therapy with a hyaluronan-degrading enzyme and an immune checkpoint inhibitor |
JP7286267B2 (en) | 2014-08-28 | 2023-06-05 | バイオアトラ インコーポレイテッド | Conditionally active chimeric antigen receptor for modified T cells |
MX2017002805A (en) | 2014-09-03 | 2017-12-20 | Bioatla Llc | Discovering and producing conditionally active biologic proteins in the same eukaryotic cell production hosts. |
CA2960712A1 (en) | 2014-09-08 | 2016-03-17 | Academia Sinica | Human inkt cell activation using glycolipids |
US20180010132A1 (en) | 2014-09-11 | 2018-01-11 | Novartis Ag | Inhibition of prmt5 to treat mtap-deficiency-related diseases |
CA2959545A1 (en) | 2014-09-15 | 2016-03-24 | Genentech, Inc. | Antibody formulations |
US10222386B2 (en) | 2014-09-19 | 2019-03-05 | The Johns Hopkins University | Biomarkers of congnitive dysfunction |
WO2016054259A1 (en) | 2014-10-01 | 2016-04-07 | Arsia Therapeutics, Inc. | Polysaccharide and nucleic acid formulations containing viscosity-lowering agents |
BR112017007765B1 (en) | 2014-10-14 | 2023-10-03 | Halozyme, Inc | COMPOSITIONS OF ADENOSINE DEAMINASE-2 (ADA2), VARIANTS THEREOF AND METHODS OF USING THE SAME |
ES2808153T3 (en) | 2014-10-31 | 2021-02-25 | Mereo Biopharma 5 Inc | Combination therapy for disease treatment |
SI3215525T1 (en) | 2014-11-05 | 2020-11-30 | Genentech, Inc. | Methods of producing two chain proteins in bacteria |
RU2017119185A (en) | 2014-11-05 | 2018-12-05 | Дженентек, Инк. | ANTIBODIES AGAINST FGFR2 / 3 AND WAYS OF THEIR APPLICATION |
KR20170075793A (en) | 2014-11-05 | 2017-07-03 | 제넨테크, 인크. | Methods of producing two chain proteins in bacteria |
SG11201703667SA (en) | 2014-11-05 | 2017-06-29 | Annexon Inc | Humanized anti-complement factor c1q antibodies and uses thereof |
WO2016073157A1 (en) | 2014-11-06 | 2016-05-12 | Genentech, Inc. | Anti-ang2 antibodies and methods of use thereof |
CN107073126A (en) | 2014-11-06 | 2017-08-18 | 豪夫迈·罗氏有限公司 | Combination treatment comprising OX40 combinations activator and TIGIT inhibitor |
EP3215519A1 (en) | 2014-11-06 | 2017-09-13 | Novartis AG | Amatoxin derivatives and conjugates thereof as inhibitors of rna polymerase |
EP3218403B1 (en) | 2014-11-10 | 2020-05-13 | F.Hoffmann-La Roche Ag | Anti-interleukin-33 antibodies and uses thereof |
MY191423A (en) | 2014-11-10 | 2022-06-27 | Medimmune Ltd | Binding molecules specific for cd73 and uses thereof |
EP3552488A1 (en) | 2014-11-10 | 2019-10-16 | F. Hoffmann-La Roche AG | Animal model for nephropathy and agents for treating the same |
WO2016075176A1 (en) | 2014-11-11 | 2016-05-19 | Medimmune Limited | Therapeutic combinations comprising anti-cd73 antibodies and a2a receptor inhibitor and uses thereof |
BR112017010198A2 (en) | 2014-11-17 | 2017-12-26 | Genentech Inc | combination therapy comprising ox40 binding agonists and pd-1 axis binding antagonists |
EP3221353A1 (en) | 2014-11-19 | 2017-09-27 | Nestec S.A. | Antibodies against serotonin, tryptophan and kynurenine metabolites and uses thereof |
WO2016081808A1 (en) | 2014-11-20 | 2016-05-26 | The Regents Of The University Of California | Compositions and methods related to hematologic recovery |
WO2016089883A1 (en) | 2014-12-01 | 2016-06-09 | Novartis Ag | Compositions and methods for diagnosis and treatment of prostate cancer |
EP3227341A1 (en) | 2014-12-02 | 2017-10-11 | CeMM - Forschungszentrum für Molekulare Medizin GmbH | Anti-mutant calreticulin antibodies and their use in the diagnosis and therapy of myeloid malignancies |
PL3227332T3 (en) | 2014-12-03 | 2020-06-15 | F. Hoffmann-La Roche Ag | Multispecific antibodies |
EP3227337A1 (en) | 2014-12-05 | 2017-10-11 | F. Hoffmann-La Roche AG | Methods and compositions for treating cancer using pd-1 axis antagonists and hpk1 antagonists |
EP3029032A1 (en) | 2014-12-05 | 2016-06-08 | Centre National de la Recherche Scientifique (CNRS) | Bifunctional do2pa derivatives, chelates with metallic cations and use thereof |
US10093733B2 (en) | 2014-12-11 | 2018-10-09 | Abbvie Inc. | LRP-8 binding dual variable domain immunoglobulin proteins |
ES2870983T3 (en) | 2014-12-19 | 2021-10-28 | Univ Nantes | Anti-IL-34 antibodies |
UY36449A (en) | 2014-12-19 | 2016-07-29 | Novartis Ag | COMPOSITIONS AND METHODS FOR ANTIBODIES DIRECTED TO BMP6 |
CN113150165A (en) | 2014-12-22 | 2021-07-23 | 西雅图免疫公司 | Bispecific tetravalent antibodies and methods of making and using same |
CN107530423B (en) | 2015-01-14 | 2022-04-05 | 布里格姆及妇女医院股份有限公司 | Treatment of cancer with anti-LAP monoclonal antibodies |
US10495645B2 (en) | 2015-01-16 | 2019-12-03 | Academia Sinica | Cancer markers and methods of use thereof |
US9975965B2 (en) | 2015-01-16 | 2018-05-22 | Academia Sinica | Compositions and methods for treatment and detection of cancers |
JP6779887B2 (en) | 2015-01-24 | 2020-11-04 | アカデミア シニカAcademia Sinica | New glycan conjugate and how to use it |
AU2016209056B2 (en) | 2015-01-24 | 2021-01-28 | Academia Sinica | Cancer markers and methods of use thereof |
JP2018506275A (en) | 2015-01-28 | 2018-03-08 | ジェネンテック, インコーポレイテッド | Gene expression markers and treatment of multiple sclerosis |
KR102620346B1 (en) | 2015-01-30 | 2024-01-02 | 아카데미아 시니카 | Compositions and Methods Related to Universal Glycoforms for Enhanced Antibody Efficacy |
MA41451A (en) | 2015-02-04 | 2017-12-12 | Univ Washington | ANTI-TAU CONSTRUCTIONS |
JP2018512597A (en) | 2015-02-04 | 2018-05-17 | ジェネンテック, インコーポレイテッド | Mutant smoothened and method of using the same |
AU2016219534B2 (en) | 2015-02-09 | 2021-07-01 | Massachusetts Institute Of Technology | Multi-specific antibodies with affinity for human A33 antigen and dota metal complex and uses thereof |
US20170151281A1 (en) | 2015-02-19 | 2017-06-01 | Batu Biologics, Inc. | Chimeric antigen receptor dendritic cell (car-dc) for treatment of cancer |
TWI691512B (en) * | 2015-02-20 | 2020-04-21 | 日商橘生藥品工業股份有限公司 | Fc fusion high affinity IgE receptor alpha chain |
EP3262064A1 (en) | 2015-02-23 | 2018-01-03 | Seagull Therapeutics SAS | Non-natural semaphorins 3 and their medical use |
US10800846B2 (en) | 2015-02-26 | 2020-10-13 | Merck Patent Gmbh | PD-1/PD-L1 inhibitors for the treatment of cancer |
KR20170120601A (en) | 2015-02-26 | 2017-10-31 | 제넨테크, 인크. | How to Treat Integrin Beta 7 Antagonists and Crohn's Disease |
EP3265557B1 (en) | 2015-03-06 | 2019-10-16 | F. Hoffmann-La Roche AG | Ultrapurified dsba and dsbc and methods of making and using the same |
US20180111989A1 (en) | 2015-04-01 | 2018-04-26 | Hadasit Medical Research Services And Development Ltd. | Inhibitors of neuroligin 4 - neurexin 1-beta protein-protein interaction for treatment of liver disorders |
US11279768B1 (en) | 2015-04-03 | 2022-03-22 | Precision Biologics, Inc. | Anti-cancer antibodies, combination therapies, and uses thereof |
EP4249916A3 (en) | 2015-04-06 | 2023-11-01 | President and Fellows of Harvard College | Compositions and methods for non-myeloablative conditioning |
MX2017012805A (en) | 2015-04-07 | 2018-04-11 | Genentech Inc | Antigen binding complex having agonistic activity and methods of use. |
DK3280441T3 (en) | 2015-04-07 | 2021-11-15 | Alector Llc | ANTI-SORTILINE ANTIBODIES AND PROCEDURES FOR USE |
WO2016164799A1 (en) | 2015-04-10 | 2016-10-13 | The Regents Of The University Of California | Methods of determining patient populations amenable to immunomodulatory treatment of cancer |
SI3286315T1 (en) | 2015-04-24 | 2021-09-30 | F. Hoffmann-La Roche Ag | Methods of identifying bacteria comprising binding polypeptides |
AU2016252773B2 (en) | 2015-04-24 | 2022-06-02 | Genentech, Inc. | Multispecific antigen-binding proteins |
JP6963508B2 (en) | 2015-05-11 | 2021-11-10 | ジェネンテック, インコーポレイテッド | Compositions and Methods for Treating Lupus Nephritis |
CN107921126A (en) | 2015-05-22 | 2018-04-17 | 转化药物开发有限责任公司 | The composition and its application method of benzamide and reactive compound |
WO2016191750A1 (en) | 2015-05-28 | 2016-12-01 | Genentech, Inc. | Cell-based assay for detecting anti-cd3 homodimers |
KR20180013881A (en) | 2015-05-29 | 2018-02-07 | 제넨테크, 인크. | PD-L1 promoter methylation in cancer |
CN107810012A (en) | 2015-06-02 | 2018-03-16 | 豪夫迈·罗氏有限公司 | Use the composition and method of the anti-Antybody therapy sacred diseases of IL 34 |
PE20180041A1 (en) | 2015-06-05 | 2018-01-09 | Novartis Ag | ANTIBODIES TARGETING BONE MORPHOGENETIC PROTEIN (BMP9) AND METHODS FROM THESE |
US20180296537A1 (en) | 2015-06-05 | 2018-10-18 | Novartis Ag | Methods and compositions for diagnosing, treating, and monitoring treatment of shank3 deficiency associated disorders |
US11174313B2 (en) | 2015-06-12 | 2021-11-16 | Alector Llc | Anti-CD33 antibodies and methods of use thereof |
SG10201912085WA (en) | 2015-06-12 | 2020-02-27 | Alector Llc | Anti-cd33 antibodies and methods of use thereof |
TW201710286A (en) | 2015-06-15 | 2017-03-16 | 艾伯維有限公司 | Binding proteins against VEGF, PDGF, and/or their receptors |
CA2989586A1 (en) | 2015-06-16 | 2016-12-22 | Pfizer, Inc. | Pd-l1 antagonist combination treatments |
US20190194315A1 (en) | 2015-06-17 | 2019-06-27 | Novartis Ag | Antibody drug conjugates |
EP3310815A1 (en) | 2015-06-17 | 2018-04-25 | F. Hoffmann-La Roche AG | Methods of treating locally advanced or metastatic breast cancers using pd-1 axis binding antagonists and taxanes |
CA2987797A1 (en) | 2015-06-17 | 2016-12-22 | Christopher Robert Bebbington | Methods and compositions for treating fibrotic diseases |
JOP20200312A1 (en) | 2015-06-26 | 2017-06-16 | Novartis Ag | Factor xi antibodies and methods of use |
RS61452B9 (en) | 2015-06-29 | 2021-12-31 | Immunogen Inc | Anti-cd123 antibodies and conjugates and derivatives thereof |
CA2989936A1 (en) | 2015-06-29 | 2017-01-05 | Genentech, Inc. | Type ii anti-cd20 antibody for use in organ transplantation |
WO2017023866A1 (en) | 2015-07-31 | 2017-02-09 | Boston Biomedical, Inc. | Method of targeting stat3 and other non-druggable proteins |
EP3331914A1 (en) | 2015-08-03 | 2018-06-13 | Novartis AG | Methods of treating fgf21-associated disorders |
TW202340452A (en) | 2015-08-04 | 2023-10-16 | 美商再生元醫藥公司 | Taurine supplemented cell culture medium and methods of use |
CN105384825B (en) | 2015-08-11 | 2018-06-01 | 南京传奇生物科技有限公司 | A kind of bispecific chimeric antigen receptor and its application based on single domain antibody |
KR20180054639A (en) | 2015-08-28 | 2018-05-24 | 알렉터 엘엘씨 | Anti-SIGLEC-7 Antibodies and Methods of Use Thereof |
ES2924071T3 (en) | 2015-09-02 | 2022-10-04 | Yissum Res Dev Co Of Hebrew Univ Jerusalem Ltd | Specific antibodies to human T-cell immunoglobulin and ITIM domain (TIGIT) |
US10935544B2 (en) | 2015-09-04 | 2021-03-02 | Obi Pharma, Inc. | Glycan arrays and method of use |
TN2018000076A1 (en) | 2015-09-09 | 2019-07-08 | Novartis Ag | Thymic stromal lymphopoietin (tslp)-binding molecules and methods of using the molecules |
DK3347377T3 (en) | 2015-09-09 | 2021-05-10 | Novartis Ag | Thymic stromal lymphopoietin (TSLP) -binding antibodies and methods of using the antibodies |
US10894988B2 (en) | 2015-09-11 | 2021-01-19 | The Board Of Trustees Of The Leland Stanford Junior University | Method of determining the prognosis of hepatocellular carcinomas using a multigene signature associated with metastasis |
US9862760B2 (en) | 2015-09-16 | 2018-01-09 | Novartis Ag | Polyomavirus neutralizing antibodies |
WO2017053705A1 (en) | 2015-09-23 | 2017-03-30 | Oncomed Pharmaceuticals, Inc. | Methods and compositions for treatment of cancer |
BR112018005931A2 (en) | 2015-09-24 | 2018-10-09 | Abvitro Llc | hiv antibody compositions and methods of use |
US10954300B2 (en) | 2015-09-28 | 2021-03-23 | The Trustees Of Columbia University In The City Of New York | Use of pentoxifylline with immune checkpoint-blockade therapies for the treatment of melanoma |
US20180282415A1 (en) | 2015-09-30 | 2018-10-04 | Merck Patent Gmbh | Combination of a PD-1 Axis Binding Antagonist and an ALK Inhibitor for Treating ALK-Negative Cancer |
EP3359572A2 (en) | 2015-10-06 | 2018-08-15 | H. Hoffnabb-La Roche Ag | Method for treating multiple sclerosis |
CN117069841A (en) | 2015-10-06 | 2023-11-17 | 艾利妥 | anti-TREM 2 antibodies and methods of use thereof |
US11161912B2 (en) | 2015-10-13 | 2021-11-02 | Technion Research & Development Foundation Limited | Heparanase-neutralizing monoclonal antibodies |
EP3370515B1 (en) | 2015-10-21 | 2022-01-26 | Redcoat Solutions, Inc. | Bed bugs detection device |
HRP20231035T1 (en) | 2015-10-21 | 2023-12-22 | Redcoat Solutions, Inc. | Anti-bed bug monoclonal antibodies and methods of making and uses thereof |
US10604577B2 (en) | 2015-10-22 | 2020-03-31 | Allakos Inc. | Methods and compositions for treating systemic mastocytosis |
WO2017074774A1 (en) | 2015-10-28 | 2017-05-04 | Yale University | Humanized anti-dkk2 antibody and uses thereof |
EP3368575A2 (en) | 2015-10-29 | 2018-09-05 | Alector LLC | Anti-siglec-9 antibodies and methods of use thereof |
PL3374398T3 (en) | 2015-11-10 | 2020-08-24 | Medimmune, Llc | Binding molecules specific for asct2 and uses thereof |
CN106729743B (en) | 2015-11-23 | 2021-09-21 | 四川科伦博泰生物医药股份有限公司 | anti-ErbB 2 antibody-drug conjugate, and composition, preparation method and application thereof |
WO2017089593A1 (en) | 2015-11-26 | 2017-06-01 | Universite Paris Descartes | Inhibitors for treating or preventing a pulmonary arterial hypertension in systemic sclerosis patients and method for diagnosing said disease |
LT3390441T (en) | 2015-12-15 | 2021-11-10 | Gilead Sciences, Inc. | Human immunodeficiency virus neutralizing antibodies |
JP6949025B2 (en) | 2015-12-17 | 2021-10-13 | ヤンセン ファーマシューティカ エヌ.ベー. | Antibodies to risperidone and its use |
EP3390455A1 (en) | 2015-12-17 | 2018-10-24 | Janssen Pharmaceutica NV | Antibodies to quetiapine and use thereof |
UY37030A (en) | 2015-12-18 | 2017-07-31 | Novartis Ag | ANTIBODIES DIRECTED TO CD32B AND METHODS OF USE OF THE SAME |
EP3395835B1 (en) | 2015-12-25 | 2021-02-03 | Chugai Seiyaku Kabushiki Kaisha | Antibody having enhanced activity, and method for modifying same |
CN115400220A (en) | 2015-12-30 | 2022-11-29 | 豪夫迈·罗氏有限公司 | Preparation for reducing degradation of polysorbate |
WO2017117304A1 (en) | 2015-12-30 | 2017-07-06 | Genentech, Inc. | Use of tryptophan derivatives for protein formulations |
ES2837428T3 (en) | 2016-01-08 | 2021-06-30 | Hoffmann La Roche | CEA-Positive Cancer Treatment Procedures Using PD-1 Axis Binding Antagonists and Anti-CEA / Anti-CD3 Bispecific Antibodies |
CN116003593A (en) | 2016-01-11 | 2023-04-25 | 苏黎世大学 | Immunostimulatory humanized monoclonal antibodies directed against human interleukin-2 and fusion proteins thereof |
ES2847155T3 (en) | 2016-01-21 | 2021-08-02 | Novartis Ag | Multispecific molecules targeting CLL-1 |
EP3408671B1 (en) | 2016-01-25 | 2023-11-01 | F. Hoffmann-La Roche AG | Methods for assaying t-cell dependent bispecific antibodies |
JP2019509721A (en) | 2016-02-04 | 2019-04-11 | キュリス,インコーポレイテッド | Mutant smoothened and method of using the same |
MA43088B1 (en) | 2016-02-19 | 2020-10-28 | Morphosys Ag | Anti-il-17c antibodies |
US11066456B2 (en) | 2016-02-25 | 2021-07-20 | Washington University | Compositions comprising TREM2 and methods of use thereof |
EP4043492A1 (en) | 2016-03-01 | 2022-08-17 | Yissum Research Development Company of the Hebrew University of Jerusalem Ltd. | Antibodies specific to human poliovirus receptor (pvr) |
US11472877B2 (en) | 2016-03-04 | 2022-10-18 | Alector Llc | Anti-TREM1 antibodies and methods of use thereof |
ES2804907T3 (en) | 2016-03-04 | 2021-02-09 | Morphosys Ag | Polypeptide Library |
EP3216458A1 (en) | 2016-03-07 | 2017-09-13 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Modified vascular endothelial growth factor a (vegf-a) and its medical use |
CN109195996A (en) | 2016-03-08 | 2019-01-11 | 中央研究院 | The modularity synthetic method of N- glycan and its array |
CN116284392A (en) | 2016-03-10 | 2023-06-23 | 艾科赛扬制药股份有限公司 | Activin type 2 receptor binding proteins and uses thereof |
ES2904286T3 (en) | 2016-03-15 | 2022-04-04 | Chugai Pharmaceutical Co Ltd | Cancer Treatment Methods Using PD-1 Axis Binding Antagonists and Anti-GPC3 Antibodies |
WO2017161206A1 (en) | 2016-03-16 | 2017-09-21 | Halozyme, Inc. | Conjugates containing conditionally active antibodies or antigen-binding fragments thereof, and methods of use |
WO2017162791A1 (en) | 2016-03-23 | 2017-09-28 | Prothix Bv | Monoclonal antibodies against the active site of factor xi and uses thereof |
CN109311995A (en) | 2016-03-29 | 2019-02-05 | 台湾浩鼎生技股份有限公司 | Antibody, pharmaceutical composition and method |
WO2017172981A2 (en) | 2016-03-29 | 2017-10-05 | University Of Southern California | Chimeric antigen receptors targeting cancer |
US10980894B2 (en) | 2016-03-29 | 2021-04-20 | Obi Pharma, Inc. | Antibodies, pharmaceutical compositions and methods |
US11768203B2 (en) | 2016-03-31 | 2023-09-26 | University Of Southern California | Highly sensitive and specific luciferase based reporter assay for antigen detection |
BR112018071683A2 (en) | 2016-04-22 | 2019-02-19 | Obi Pharma, Inc. | method for treating breast cancer, method for treating a tumor in a patient, method for treating an individual suffering from cancer by immunotherapy, method for inducing / improving an immune response in an individual, method for improving obi-822 induced vaccine by immune response in an individual in need thereof, method for identifying a patient suitable for cancer therapy, and method for determining a patient's cancer treatment prognosis or drug response |
US10875919B2 (en) | 2016-04-26 | 2020-12-29 | Alector Llc | Chimeric receptors and methods of use thereof |
JP7138567B2 (en) | 2016-04-27 | 2022-09-16 | ノバルティス アーゲー | Antibodies against growth differentiation factor 15 and their uses |
US10464969B2 (en) | 2016-05-05 | 2019-11-05 | Novartis Ag | Amatoxin derivatives and conjugates thereof as inhibitors of RNA polymerase |
ES2930255T3 (en) | 2016-05-13 | 2022-12-09 | Bioatla Inc | Anti-Ror2 antibodies, antibody fragments, their immunoconjugates and uses thereof |
AU2017268234A1 (en) | 2016-05-17 | 2018-12-13 | Genentech, Inc. | Stromal gene signatures for diagnosis and use in immunotherapy |
TW201802121A (en) | 2016-05-25 | 2018-01-16 | 諾華公司 | Reversal binding agents for anti-factor XI/XIa antibodies and uses thereof |
CA3025391A1 (en) | 2016-05-26 | 2017-11-30 | Merck Patent Gmbh | Pd-1 / pd-l1 inhibitors for cancer treatment |
SG11201810678WA (en) | 2016-06-02 | 2018-12-28 | Abbvie Inc | Glucocorticoid receptor agonist and immunoconjugates thereof |
US10851159B2 (en) | 2016-06-02 | 2020-12-01 | Bloom Diagnostics Ag | Antibodies that bind to human anti-Müllerian hormone (AMH) and their uses |
WO2017216724A1 (en) | 2016-06-15 | 2017-12-21 | Novartis Ag | Methods for treating disease using inhibitors of bone morphogenetic protein 6 (bmp6) |
AU2017286676A1 (en) | 2016-06-17 | 2018-12-13 | F. Hoffmann La-Roche Ag | Purification of multispecific antibodies |
EP3263706A1 (en) | 2016-06-28 | 2018-01-03 | Centre National De La Recherche Scientifique (Cnrs) | Agents targeting snat7 for treating cellular metabolism reprogramming-associated diseases |
EP3686287A1 (en) | 2016-06-28 | 2020-07-29 | Hifibio | Method for transcriptome analysis of single cells |
WO2018011691A1 (en) | 2016-07-12 | 2018-01-18 | Nestec S.A. | Competitive immunoassay methods |
WO2018014260A1 (en) | 2016-07-20 | 2018-01-25 | Nanjing Legend Biotech Co., Ltd. | Multispecific antigen binding proteins and methods of use thereof |
KR20230117482A (en) | 2016-07-27 | 2023-08-08 | 오비아이 파머 인코퍼레이티드 | Immunogenic/therapeutic glycan compositions and uses thereof |
KR102528998B1 (en) | 2016-07-29 | 2023-05-03 | 오비아이 파머 인코퍼레이티드 | Human Antibodies, Pharmaceutical Compositions and Methods |
JP7219207B2 (en) | 2016-07-29 | 2023-02-07 | アンスティチュ ナショナル ドゥ ラ サンテ エ ドゥ ラ ルシェルシュ メディカル | Antibodies targeting tumor-associated macrophages and uses thereof |
WO2018026969A2 (en) | 2016-08-03 | 2018-02-08 | Achaogen, Inc. | Plazomicin antibodies and methods of use |
EP3494139B1 (en) | 2016-08-05 | 2022-01-12 | F. Hoffmann-La Roche AG | Multivalent and multiepitopic anitibodies having agonistic activity and methods of use |
JP2019528312A (en) | 2016-08-07 | 2019-10-10 | ノバルティス アーゲー | mRNA-mediated immunization methods |
CN109476748B (en) | 2016-08-08 | 2023-05-23 | 豪夫迈·罗氏有限公司 | Methods for treatment and diagnosis of cancer |
SG11201901228QA (en) | 2016-08-15 | 2019-03-28 | Genentech Inc | Chromatography method for quantifying a non-ionic surfactant in a composition comprising the non-ionic surfactant and a polypeptide |
AU2017312785A1 (en) | 2016-08-16 | 2019-01-24 | Regeneron Pharmaceuticals, Inc. | Methods for quantitating individual antibodies from a mixture |
CA3034057A1 (en) | 2016-08-22 | 2018-03-01 | CHO Pharma Inc. | Antibodies, binding fragments, and methods of use |
US11066477B2 (en) | 2016-08-31 | 2021-07-20 | Oncotherapy Science, Inc. | Monoclonal antibody against MELK and utilization thereof |
US20190225682A1 (en) | 2016-09-02 | 2019-07-25 | 180 Therapeutics Lp | Method of treating localized fibrotic disorders using an il-33/tnf bispecific antibody |
US20190202907A1 (en) | 2016-09-02 | 2019-07-04 | 180 Therapeutics Lp | Method of treating systemic fibrotic disorders using an il-33/tnf bispecific antibody |
WO2018049083A1 (en) | 2016-09-07 | 2018-03-15 | The Regents Of The University Of California | Antibodies to oxidation-specific epitopes |
WO2018049261A1 (en) | 2016-09-09 | 2018-03-15 | Icellhealth Consulting Llc | Oncolytic virus expressing immune checkpoint modulators |
AU2017327828B2 (en) | 2016-09-16 | 2023-11-16 | Shanghai Henlius Biotech, Inc. | Anti-PD-1 antibodies |
JOP20190009A1 (en) | 2016-09-21 | 2019-01-27 | Alx Oncology Inc | Antibodies against signal-regulatory protein alpha and methods of use |
TWI762516B (en) | 2016-10-06 | 2022-05-01 | 日商腫瘤療法 科學股份有限公司 | Monoclonal antibodies against FZD10 and their uses |
IL265762B2 (en) | 2016-10-06 | 2024-04-01 | Merck Patent Gmbh | Dosing regimen of avelumab for the treatment of cancer |
WO2018068201A1 (en) | 2016-10-11 | 2018-04-19 | Nanjing Legend Biotech Co., Ltd. | Single-domain antibodies and variants thereof against ctla-4 |
KR20230119729A (en) | 2016-10-25 | 2023-08-16 | 리제너론 파아마슈티컬스, 인크. | Methods and systems for chromatography data analysis |
WO2018081531A2 (en) | 2016-10-28 | 2018-05-03 | Ariad Pharmaceuticals, Inc. | Methods for human t-cell activation |
US11078298B2 (en) | 2016-10-28 | 2021-08-03 | Banyan Biomarkers, Inc. | Antibodies to ubiquitin C-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) and related methods |
WO2018083606A1 (en) | 2016-11-01 | 2018-05-11 | Novartis Ag | Methods and compositions for enhancing gene editing |
EP3538546A1 (en) | 2016-11-14 | 2019-09-18 | Novartis AG | Compositions, methods, and therapeutic uses related to fusogenic protein minion |
CN110198703A (en) | 2016-11-21 | 2019-09-03 | 艾里奥治疗公司 | The transdermal delivery of big reagent |
KR20190077103A (en) | 2016-11-21 | 2019-07-02 | 오비아이 파머 인코퍼레이티드 | Conjugated biological molecules, pharmaceutical compositions and methods |
WO2018098363A2 (en) | 2016-11-23 | 2018-05-31 | Bioverativ Therapeutics Inc. | Bispecific antibodies binding to coagulation factor ix and coagulation factor x |
JP7080234B2 (en) | 2016-11-23 | 2022-06-03 | トランスレイショナル・ドラッグ・ディベロップメント・エルエルシー | Benzamide and active compound compositions and methods of use |
US10852271B2 (en) | 2016-12-14 | 2020-12-01 | Taiwan Semiconductor Manufacturing Co., Ltd. | On-chip heater |
CN110300761B (en) | 2016-12-15 | 2023-05-09 | 国家生物技术研究所公司 | anti-PCNA monoclonal antibodies and uses thereof |
EP3555120A1 (en) * | 2016-12-19 | 2019-10-23 | Abcam Plc | Monovalent and divalent binding proteins |
JOP20190155A1 (en) | 2016-12-21 | 2019-06-23 | Novartis Ag | Antibody drug conjugates for ablating hematopoietic stem cells |
IL267538B1 (en) | 2016-12-23 | 2024-01-01 | Novartis Ag | Anti-factor xi/xia antibodies for use in preventing, treating, managing or reducing the risk of a thromboembolic disorder or stroke in a subject |
EP3558370A2 (en) | 2016-12-23 | 2019-10-30 | Novartis AG | Methods of treatment with anti-factor xi/xia antibodies |
JOP20190187A1 (en) | 2017-02-03 | 2019-08-01 | Novartis Ag | Anti-ccr7 antibody drug conjugates |
MX2019009498A (en) | 2017-02-08 | 2019-10-02 | Novartis Ag | Fgf21 mimetic antibodies and uses thereof. |
EP3580341A4 (en) | 2017-02-09 | 2020-11-04 | Indapta Therapeutics, Inc. | Engineered natural killer (nk) cells and compositions and methods thereof |
MY197534A (en) | 2017-02-10 | 2023-06-21 | Genentech Inc | Anti-tryptase antibodies, compositions thereof, and uses thereof |
WO2018152496A1 (en) | 2017-02-17 | 2018-08-23 | The Usa, As Represented By The Secretary, Dept. Of Health And Human Services | Compositions and methods for the diagnosis and treatment of zika virus infection |
CN108456251A (en) | 2017-02-21 | 2018-08-28 | 上海君实生物医药科技股份有限公司 | Anti- PD-L1 antibody and its application |
JP2020510432A (en) | 2017-03-02 | 2020-04-09 | アンスティチュ ナショナル ドゥ ラ サンテ エ ドゥ ラ ルシェルシュ メディカル | Antibodies with specificity for NECTIN-4 and uses thereof |
EP3375889B1 (en) | 2017-03-17 | 2019-12-11 | HiFiBiO SAS | Single cell analysis |
CN110494161A (en) | 2017-03-30 | 2019-11-22 | 默克专利股份有限公司 | The combination of anti-PD-L1 antibody and DNA-PK inhibitor for treating cancer |
TW201836636A (en) | 2017-03-31 | 2018-10-16 | 公立大學法人奈良縣立醫科大學 | Medicinal composition usable for preventing and/or treating blood coagulation factor ix abnormality, comprising multispecific antigen binding molecule replacing function of blood coagulation factor viii |
US20190048055A1 (en) | 2017-03-31 | 2019-02-14 | Altor Bioscience Corporation | Alt-803 in combination with anti-cd38 antibody for cancer therapies |
US11913075B2 (en) | 2017-04-01 | 2024-02-27 | The Broad Institute, Inc. | Methods and compositions for detecting and modulating an immunotherapy resistance gene signature in cancer |
US10799597B2 (en) | 2017-04-03 | 2020-10-13 | Immunomedics, Inc. | Subcutaneous administration of antibody-drug conjugates for cancer therapy |
WO2018185618A1 (en) | 2017-04-03 | 2018-10-11 | Novartis Ag | Anti-cdh6 antibody drug conjugates and anti-gitr antibody combinations and methods of treatment |
RU2665790C1 (en) | 2017-04-17 | 2018-09-04 | Закрытое Акционерное Общество "Биокад" | Monoclonal pd-l1 antibody |
WO2018200742A1 (en) | 2017-04-25 | 2018-11-01 | The Usa, As Represented By The Secretary, Dept. Of Health And Human Services | Antibodies and methods for the diagnosis and treatment of epstein barr virus infection |
CN110799541A (en) | 2017-04-27 | 2020-02-14 | 特沙诺有限公司 | Antibody agents against lymphocyte activation gene-3 (LAG-3) and uses thereof |
CA3062439A1 (en) | 2017-05-05 | 2018-11-08 | Memorial Sloan Kettering Cancer Center | Modular self assembly disassembly (sada) technologies |
CN110831628A (en) | 2017-05-05 | 2020-02-21 | 爱乐科斯公司 | Methods and compositions for treating allergic eye diseases |
SG11202003754YA (en) | 2017-05-16 | 2020-05-28 | Bhamis Research Laboratory Pvt Ltd | High concentration protein formulations with reduced viscosity |
US11359014B2 (en) | 2017-05-16 | 2022-06-14 | Alector Llc | Anti-siglec-5 antibodies and methods of use thereof |
EP3638218A4 (en) | 2017-06-14 | 2021-06-09 | The Broad Institute, Inc. | Compositions and methods targeting complement component 3 for inhibiting tumor growth |
WO2018229715A1 (en) | 2017-06-16 | 2018-12-20 | Novartis Ag | Compositions comprising anti-cd32b antibodies and methods of use thereof |
WO2018229706A1 (en) | 2017-06-16 | 2018-12-20 | Novartis Ag | Combination therapy for the treatment of cancer |
WO2018234438A1 (en) | 2017-06-22 | 2018-12-27 | Morphosys Ag | Canine antibody libraries |
US20200123621A1 (en) | 2017-06-27 | 2020-04-23 | Dana-Farber Cancer Institute, Inc. | Compositions and methods for identifying and treating resistance to ctla4 antagonists in leukemia |
WO2019000223A1 (en) | 2017-06-27 | 2019-01-03 | Nanjing Legend Biotech Co., Ltd. | Chimeric antibody immune effctor cell engagers and methods of use thereof |
EP3655430A1 (en) | 2017-07-19 | 2020-05-27 | The U.S.A. as represented by the Secretary, Department of Health and Human Services | Antibodies and methods for the diagnosis and treatment of hepatitis b virus infection |
WO2019018729A1 (en) | 2017-07-20 | 2019-01-24 | Dana-Farber Cancer Institute, Inc. | Compositions and methods for identifying and treating metastatic small bowel neuroendocrine tumors |
WO2019020480A1 (en) | 2017-07-24 | 2019-01-31 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Antibodies and peptides to treat hcmv related diseases |
WO2019023525A1 (en) | 2017-07-28 | 2019-01-31 | Dana-Farber Cancer Institute, Inc. | Enhanced immunotherapy of cancer using targeted transcriptional modulators |
WO2019020807A1 (en) | 2017-07-28 | 2019-01-31 | Gene Signal International Sa | Cd9p-1-targeting antibody and uses thereof |
MD3601358T2 (en) | 2017-08-03 | 2023-10-31 | Alector Llc | Anti-TREM2 antibodies and methods of use thereof |
EP3589658A1 (en) | 2017-08-03 | 2020-01-08 | Alector LLC | Anti-cd33 antibodies and methods of use thereof |
MX2020000903A (en) | 2017-08-11 | 2020-07-22 | Genentech Inc | Anti-cd8 antibodies and uses thereof. |
EP3668898B1 (en) | 2017-08-14 | 2023-07-05 | MorphoSys AG | Humanized antibodies for cd3 |
BR112020005519A2 (en) | 2017-09-20 | 2020-10-27 | The University Of British Columbia | new anti-hla-a2 antibodies and their uses |
JP7382922B2 (en) | 2017-09-20 | 2023-11-17 | 中外製薬株式会社 | Dosing regimen for combination therapy using PD-1 system binding antagonists and GPC3 targeting agents |
US20230203149A1 (en) | 2017-09-25 | 2023-06-29 | Morphosys Ag | Treatment of atopic dermatitis |
EP3688007A1 (en) | 2017-09-27 | 2020-08-05 | The University of York | Bioconjugation of polypeptides |
RU2698048C2 (en) | 2017-10-03 | 2019-08-21 | Закрытое Акционерное Общество "Биокад" | Monoclonal antibody to il-5rα |
EA039662B1 (en) | 2017-10-03 | 2022-02-24 | Закрытое Акционерное Общество "Биокад" | Antibodies specific to cd47 and pd-l1 |
WO2019072870A1 (en) | 2017-10-10 | 2019-04-18 | Numab Innovation Ag | Antibodies targeting cd137 and methods of use thereof |
EP3470428A1 (en) | 2017-10-10 | 2019-04-17 | Numab Innovation AG | Antibodies targeting cd137 and methods of use thereof |
EP3470429A1 (en) | 2017-10-10 | 2019-04-17 | Numab Innovation AG | Antibodies targeting pdl1 and methods of use thereof |
CN111225926A (en) | 2017-10-10 | 2020-06-02 | 努玛治疗有限公司 | Antibodies targeting PDL1 and methods of use thereof |
EP4219540A3 (en) | 2017-10-10 | 2023-12-06 | Alpine Immune Sciences, Inc. | Ctla-4 variant immunomodulatory proteins and uses thereof |
CA3078974A1 (en) | 2017-10-12 | 2019-04-18 | Immunowake Inc. | Vegfr-antibody light chain fusion protein |
WO2019079362A1 (en) | 2017-10-16 | 2019-04-25 | Massachusetts Institute Of Technology | Mycobacterium tuberculosis host-pathogen interaction |
US20210040205A1 (en) | 2017-10-25 | 2021-02-11 | Novartis Ag | Antibodies targeting cd32b and methods of use thereof |
EP3713965A1 (en) | 2017-11-22 | 2020-09-30 | Novartis AG | Reversal binding agents for anti-factor xi/xia antibodies and uses thereof |
WO2019102456A1 (en) | 2017-11-27 | 2019-05-31 | University Of Rijeka Faculty Of Medicine | Immunotoxins for treating cancer |
CN111417651B (en) | 2017-12-01 | 2023-09-29 | 诺华股份有限公司 | Polyoma virus neutralizing antibodies |
WO2019113506A1 (en) | 2017-12-07 | 2019-06-13 | The Broad Institute, Inc. | Methods and compositions for multiplexing single cell and single nuclei sequencing |
AU2018388791A1 (en) | 2017-12-19 | 2020-07-16 | The Rockefeller University | Human IgG Fc domain variants with improved effector function |
JP7074859B2 (en) | 2017-12-22 | 2022-05-24 | エフ.ホフマン-ラ ロシュ アーゲー | Method of depletion of light chain mismatched antibody variants by hydrophobic interaction chromatography |
KR20200104886A (en) | 2017-12-28 | 2020-09-04 | 난징 레전드 바이오테크 씨오., 엘티디. | Antibodies and variants against PD-L1 |
EP3732202A4 (en) | 2017-12-28 | 2022-06-15 | Nanjing Legend Biotech Co., Ltd. | Single-domain antibodies and variants thereof against tigit |
EP3732193A1 (en) | 2017-12-29 | 2020-11-04 | Alector LLC | Anti-tmem106b antibodies and methods of use thereof |
BR112020013236A2 (en) | 2018-01-03 | 2020-12-01 | Alpine Immune Sciences, Inc. | immunomodulatory proteins from multiple domains and methods of their use |
WO2019137541A1 (en) | 2018-01-15 | 2019-07-18 | Nanjing Legend Biotech Co., Ltd. | Single-domain antibodies and variants thereof against pd-1 |
EP3746476A1 (en) | 2018-01-31 | 2020-12-09 | Alector LLC | Anti-ms4a4a antibodies and methods of use thereof |
CA3226165A1 (en) | 2018-02-09 | 2019-08-15 | Genentech, Inc. | Therapeutic and diagnostic methods for mast cell-mediated inflammatory diseases |
BR112020016400A2 (en) | 2018-02-14 | 2020-12-15 | Viela Bio, Inc. | ANTIBODIES FOR THYROSINE KINASE 3 RECEPTOR BINDER SIMILAR TO MCDONOUGH FELINE SARCOMA (FMS) (FLT3L) AND THEIR USES FOR THE TREATMENT OF AUTOIMMUNE AND INFLAMMATORY DISEASES |
US20200399376A1 (en) | 2018-02-26 | 2020-12-24 | Genentech, Inc. | Dosing for treatment with anti-tigit and anti-pd-l1 antagonist antibodies |
CA3093295A1 (en) | 2018-03-06 | 2019-09-12 | Imcare Biotech, Llc | Serine protease inhibitor kazal (spik) compositions and methods |
GB201803563D0 (en) | 2018-03-06 | 2018-04-18 | Galapagos Nv | Antibodies and pharmaceutical compositions thereof for the treatment of autoimmune skin diseases |
US11485782B2 (en) | 2018-03-14 | 2022-11-01 | Beijing Xuanyi Pharmasciences Co., Ltd. | Anti-claudin 18.2 antibodies |
WO2019175885A1 (en) | 2018-03-15 | 2019-09-19 | Biond Biologics Ltd. | Methods and compositions for decreasing soluble immune receptor cd28 |
PE20201265A1 (en) | 2018-03-21 | 2020-11-19 | Alx Oncology Inc | ANTIBODIES AGAINST SIGNAL REGULATORY ALPHA PROTEIN AND METHODS OF USE |
CN111886254B (en) | 2018-03-30 | 2023-12-08 | 南京传奇生物科技有限公司 | Single domain antibodies against LAG-3 and uses thereof |
EP3774883A1 (en) | 2018-04-05 | 2021-02-17 | Gilead Sciences, Inc. | Antibodies and fragments thereof that bind hepatitis b virus protein x |
MX2020010729A (en) | 2018-04-13 | 2021-03-09 | Genentech Inc | Stable anti-cd79b immunoconjugate formulations. |
EP3781209B1 (en) | 2018-04-16 | 2023-08-30 | Merck Patent GmbH | Viscosity reduction of highly concentrated protein formulations |
US11957695B2 (en) | 2018-04-26 | 2024-04-16 | The Broad Institute, Inc. | Methods and compositions targeting glucocorticoid signaling for modulating immune responses |
EP3788071A1 (en) | 2018-05-02 | 2021-03-10 | The United States Of America, As Represented By The Secretary, Department of Health and Human Services | Antibodies and methods for the diagnosis, prevention, and treatment of epstein barr virus infection |
WO2019213660A2 (en) | 2018-05-04 | 2019-11-07 | The Broad Institute, Inc. | Compositions and methods for modulating cgrp signaling to regulate innate lymphoid cell inflammatory responses |
TW202014201A (en) | 2018-05-04 | 2020-04-16 | 德商馬克專利公司 | COMBINED INHIBITION OF PD-1/PD-L1, TGFβ AND DNA-PK FOR THE TREATMENT OF CANCER |
JP2021522801A (en) | 2018-05-09 | 2021-09-02 | イッサム リサーチ デベロップメント カンパニー オブ ザ ヘブリュー ユニバーシティー オブ エルサレム リミテッド | Antibodies specific for humannectin 4 |
KR20210021467A (en) | 2018-05-14 | 2021-02-26 | 웨어울프 세라퓨틱스, 인크. | Activatable interleukin-2 polypeptide and method of use thereof |
BR112020023118A2 (en) | 2018-05-14 | 2021-04-13 | Werewolf Therapeutics, Inc. | ACTIVE ACTIVABLE INTERLEUKIN POLYPEPTIDS 12 AND METHODS OF USE OF THESE |
US11542329B2 (en) | 2018-05-16 | 2023-01-03 | Morphosys Ag | Antibodies targeting Glycoprotein VI |
AU2019274782A1 (en) | 2018-05-24 | 2020-12-03 | Ares Trading S.A. | Method for controlling the afucosylation level of a glycoprotein composition |
UA128113C2 (en) | 2018-05-25 | 2024-04-10 | ЕЛЕКТОР ЕлЕлСі | Anti-sirpa antibodies and methods of use thereof |
JP7360401B2 (en) | 2018-05-31 | 2023-10-12 | グリコネックス インコーポレイテッド | Therapeutic antibodies that bind biantennary Lewis B and Lewis Y antigens |
EP3801766A1 (en) | 2018-05-31 | 2021-04-14 | Novartis AG | Hepatitis b antibodies |
WO2019232542A2 (en) | 2018-06-01 | 2019-12-05 | Massachusetts Institute Of Technology | Methods and compositions for detecting and modulating microenvironment gene signatures from the csf of metastasis patients |
EP3802611A2 (en) | 2018-06-01 | 2021-04-14 | Novartis AG | Binding molecules against bcma and uses thereof |
WO2019236965A1 (en) | 2018-06-08 | 2019-12-12 | Alector Llc | Anti-siglec-7 antibodies and methods of use thereof |
AR115571A1 (en) | 2018-06-20 | 2021-02-03 | Novartis Ag | DRUG ANTIBODY CONJUGATES FOR HEMATOPOIETIC STEM CELL ABLATION |
BR112020026384A2 (en) | 2018-06-23 | 2021-03-30 | Genentech, Inc. | METHODS FOR TREATING AN INDIVIDUAL WITH LUNG CANCER AND FOR TREATING AN INDIVIDUAL WITH SMALL CELL LUNG CANCER, KITS, ANTIBODY ANTI-PD-L1 AND COMPOSITION |
US11203645B2 (en) | 2018-06-27 | 2021-12-21 | Obi Pharma, Inc. | Glycosynthase variants for glycoprotein engineering and methods of use |
CA3099176A1 (en) | 2018-06-29 | 2020-01-02 | Alector Llc | Anti-sirp-beta1 antibodies and methods of use thereof |
TW202005694A (en) | 2018-07-02 | 2020-02-01 | 美商里珍納龍藥品有限公司 | Systems and methods for preparing a polypeptide from a mixture |
WO2020007822A1 (en) | 2018-07-02 | 2020-01-09 | Conservatoire National Des Arts Et Metiers (Cnam) | Bismuth metallic (0) nanoparticles, process of manufacturing and uses thereof |
TW202011995A (en) | 2018-07-03 | 2020-04-01 | 比利時商葛萊伯格有限公司 | High concentration liquid antibody formulations |
LT3618928T (en) | 2018-07-13 | 2023-04-11 | Alector Llc | Anti-sortilin antibodies and methods of use thereof |
CA3104147A1 (en) | 2018-07-18 | 2020-01-23 | Genentech, Inc. | Methods of treating lung cancer with a pd-1 axis binding antagonist, an antimetabolite, and a platinum agent |
EP3830123A1 (en) | 2018-07-27 | 2021-06-09 | Alector LLC | Anti-siglec-5 antibodies and methods of use thereof |
BR112021002130A2 (en) | 2018-08-08 | 2021-05-04 | Genentech, Inc. | liquid formulation, article of manufacture or kit and method for reducing oxidation of a polypeptide |
AU2019324170A1 (en) | 2018-08-23 | 2021-02-18 | Seagen, Inc. | Anti-TIGIT antibodies |
SG11202101552SA (en) | 2018-08-31 | 2021-03-30 | Alector Llc | Anti-cd33 antibodies and methods of use thereof |
WO2020053742A2 (en) | 2018-09-10 | 2020-03-19 | Novartis Ag | Anti-hla-hbv peptide antibodies |
WO2020053122A1 (en) | 2018-09-10 | 2020-03-19 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Combination of her2/neu antibody with heme for treating cancer |
EP4249917A3 (en) | 2018-09-21 | 2023-11-08 | F. Hoffmann-La Roche AG | Diagnostic methods for triple-negative breast cancer |
EP3856251A1 (en) | 2018-09-26 | 2021-08-04 | Merck Patent GmbH | Combination of a pd-1 antagonist, an atr inhibitor and a platinating agent for the treatment of cancer |
AU2019347751A1 (en) | 2018-09-27 | 2021-04-29 | Xilio Development, Inc. | Masked cytokine polypeptides |
EP3636320A1 (en) | 2018-10-09 | 2020-04-15 | Numab Therapeutics AG | Antibodies targeting cd137 and methods of use thereof |
WO2020074584A1 (en) | 2018-10-09 | 2020-04-16 | Numab Therapeutics AG | Antibodies targeting cd137 and methods of use thereof |
US20210340277A1 (en) | 2018-10-11 | 2021-11-04 | The Scripps Research Institute | Antibody compounds with reactive arginine and related antibody drug conjugates |
WO2020077236A1 (en) | 2018-10-12 | 2020-04-16 | The Broad Institute, Inc. | Method for extracting nuclei or whole cells from formalin-fixed paraffin-embedded tissues |
CN113164447A (en) | 2018-10-15 | 2021-07-23 | 默克专利股份公司 | Combination therapy with DNA alkylating agents and ATR inhibitors |
WO2020081730A2 (en) | 2018-10-16 | 2020-04-23 | Massachusetts Institute Of Technology | Methods and compositions for modulating microenvironment |
RU2724469C2 (en) | 2018-10-31 | 2020-06-23 | Закрытое Акционерное Общество "Биокад" | Monoclonal antibody which specifically binds to cd20 |
US20200140533A1 (en) | 2018-11-02 | 2020-05-07 | Annexon, Inc. | Compositions and methods for treating brain injury |
EP3877407A1 (en) | 2018-11-05 | 2021-09-15 | F. Hoffmann-La Roche AG | Methods of producing two chain proteins in prokaryotic host cells |
GB201818477D0 (en) | 2018-11-13 | 2018-12-26 | Emstopa Ltd | Tissue plasminogen activator antibodies and method of use thereof |
GB201818622D0 (en) | 2018-11-15 | 2019-01-02 | Amlo Biosciences Ltd | Monoclonal antibodies against loricrin |
GB201818618D0 (en) | 2018-11-15 | 2019-01-02 | Amlo Biosciences Ltd | Monoclonal antibodies against ambra-1 |
KR20210123289A (en) | 2018-11-21 | 2021-10-13 | 인답타 세라뷰틱스 인코포레이티드 | Methods and related compositions and methods for propagation of natural killer cell subsets |
CA3119043A1 (en) | 2018-12-03 | 2020-06-11 | Eirion Therapeutics, Inc. | Improved delivery of large agents |
CA3121699A1 (en) | 2018-12-05 | 2020-06-11 | Morphosys Ag | Multispecific antigen-binding molecules |
TWI821474B (en) | 2018-12-07 | 2023-11-11 | 大陸商江蘇恆瑞醫藥股份有限公司 | Cd3 antibody and its pharmaceutical use thereof |
EP3893841A1 (en) | 2018-12-14 | 2021-10-20 | MorphoSys AG | Antibody formulations |
CN113557244A (en) | 2018-12-18 | 2021-10-26 | 弹射器治疗有限公司 | Use of anti-CCR 7 mAbs to prevent or treat graft versus host disease (GvHD) |
AR117343A1 (en) | 2018-12-18 | 2021-07-28 | Novartis Ag | REVERSIBLE BINDING AGENTS FOR ANTI-FACTOR XI / XIa ANTIBODIES AND USES OF THEM |
TW202039554A (en) | 2018-12-19 | 2020-11-01 | 瑞士商諾華公司 | Anti-tnf-alpha antibodies |
CA3121804A1 (en) | 2018-12-21 | 2020-06-25 | Genentech, Inc. | Methods of producing polypeptides using a cell line resistant to apoptosis |
WO2020125744A1 (en) | 2018-12-21 | 2020-06-25 | 江苏恒瑞医药股份有限公司 | Bispecific protein |
CN113195541A (en) | 2018-12-21 | 2021-07-30 | 诺华股份有限公司 | Antibodies against PMEL17 and conjugates thereof |
MX2021007768A (en) | 2018-12-26 | 2021-08-24 | Xilio Dev Inc | Anti-ctla4 antibodies and methods of use thereof. |
KR20210111792A (en) | 2018-12-28 | 2021-09-13 | 스팍스 테라퓨틱스 인크. | Binding molecules specific for claudin 18.2, compositions and methods thereof for treating cancer and other diseases |
US11739156B2 (en) | 2019-01-06 | 2023-08-29 | The Broad Institute, Inc. Massachusetts Institute of Technology | Methods and compositions for overcoming immunosuppression |
AU2020207664A1 (en) | 2019-01-13 | 2021-07-22 | University Of Rijeka Faculty Of Medicine | Antibodies specific to human Nectin-2 |
TW202043272A (en) | 2019-01-14 | 2020-12-01 | 美商建南德克公司 | Methods of treating cancer with a pd-1 axis binding antagonist and an rna vaccine |
EP3689907A1 (en) | 2019-01-31 | 2020-08-05 | Numab Therapeutics AG | Antibodies targeting il-17a and methods of use thereof |
KR20210122243A (en) | 2019-01-31 | 2021-10-08 | 누맙 세러퓨틱스 아게 | Multispecific antibodies having specificity for LNF and L-17A, antibodies targeting LLA-17A, and methods of using the same |
JP2022521773A (en) | 2019-02-27 | 2022-04-12 | ジェネンテック, インコーポレイテッド | Dosing for treatment with anti-TIGIT antibody and anti-CD20 antibody or anti-CD38 antibody |
SG11202108011UA (en) | 2019-03-01 | 2021-08-30 | Allogene Therapeutics Inc | Dll3 targeting chimeric antigen receptors and binding agents |
CN116239698A (en) | 2019-03-06 | 2023-06-09 | 江苏恒瑞医药股份有限公司 | Bifunctional fusion protein and medical application thereof |
US20220154282A1 (en) | 2019-03-12 | 2022-05-19 | The Broad Institute, Inc. | Detection means, compositions and methods for modulating synovial sarcoma cells |
US20220143148A1 (en) | 2019-03-14 | 2022-05-12 | The Broad Institute, Inc. | Compositions and methods for modulating cgrp signaling to regulate intestinal innate lymphoid cells |
MA55285A (en) | 2019-03-14 | 2022-01-19 | Morphosys Ag | ANTIBODIES TARGETING C5AR |
SG11202110032TA (en) | 2019-03-14 | 2021-10-28 | Biond Biologics Ltd | Small shedding blocking agents |
WO2020187718A1 (en) | 2019-03-15 | 2020-09-24 | Morphosys Ag | Anti-cd38 antibodies and pharmaceutical compositions thereof for the treatment of autoantibody-mediated autoimmune disease |
WO2020191069A1 (en) | 2019-03-18 | 2020-09-24 | The Broad Institute, Inc. | Modulation of type 2 immunity by targeting clec-2 signaling |
US20220185875A1 (en) | 2019-03-18 | 2022-06-16 | Jiangsu Hengrui Medicine Co., Ltd. | Bispecific antibody specifically bound to vegf and ang2 |
EP3942023A1 (en) | 2019-03-18 | 2022-01-26 | The Broad Institute, Inc. | Compositions and methods for modulating metabolic regulators of t cell pathogenicity |
CN113631573A (en) | 2019-03-25 | 2021-11-09 | 国家医疗保健研究所 | Methods of treating tauopathies by targeting new species of Tau |
CN113660953A (en) | 2019-04-01 | 2021-11-16 | 豪夫迈·罗氏有限公司 | Compositions and methods for stabilizing protein-containing formulations |
EP3956664A1 (en) | 2019-04-18 | 2022-02-23 | Genentech, Inc. | Antibody potency assay |
US20220143094A1 (en) | 2019-04-19 | 2022-05-12 | Chugai Seiyaku Kabushiki Kaisha | Chimeric receptor that recognizes engineered site in antibody |
RU2734432C1 (en) | 2019-04-23 | 2020-10-16 | Закрытое Акционерное Общество "Биокад" | Monoclonal antibody which specifically binds gitr |
EP3962947A2 (en) | 2019-05-03 | 2022-03-09 | F. Hoffmann-La Roche AG | Methods of treating cancer with an anti-pd-l1 antibody |
GB201906302D0 (en) | 2019-05-03 | 2019-06-19 | Amlo Biosciences Ltd | Methods of determining the margin of a tumour |
EP3962943A1 (en) | 2019-05-03 | 2022-03-09 | MorphoSys AG | Anti-cd19 therapy in patients having a limited number of nk cells |
GB201906297D0 (en) | 2019-05-03 | 2019-06-19 | Amlo Biosciences Ltd | Biomarkers for disease progression in squamous cell carcinoma |
JP2022531911A (en) | 2019-05-07 | 2022-07-12 | グレイセル・バイオテクノロジーズ(シャンハイ)カンパニー・リミテッド | Manipulated immune cells targeting BCMA and their use |
KR20220008311A (en) | 2019-05-14 | 2022-01-20 | 에이리온 테라퓨틱스, 인코포레이티드 | Delaying the maximum effect and/or extending the duration of the reaction |
CA3137512A1 (en) | 2019-05-14 | 2020-11-19 | Werewolf Therapeutics, Inc. | Separation moieties and methods and use thereof |
WO2020232295A1 (en) | 2019-05-16 | 2020-11-19 | Procisedx Inc. | An assay method for the detection of vcam-1 and alpha-2-macroglobulin in blood |
JP2022532381A (en) | 2019-05-16 | 2022-07-14 | プロサイセデクス インコーポレイティド | Analytical detection methods for VCAM-1 and calprotectin |
EP3972998A1 (en) | 2019-05-21 | 2022-03-30 | Novartis AG | Cd19 binding molecules and uses thereof |
EP3972993A1 (en) | 2019-05-21 | 2022-03-30 | Novartis AG | Variant cd58 domains and uses thereof |
CA3140142A1 (en) | 2019-05-21 | 2020-11-26 | Novartis Ag | Trispecific binding molecules against bcma and uses thereof |
JP2022534227A (en) | 2019-05-23 | 2022-07-28 | プロサイセデクス インコーポレイティド | Assay methods for the detection of human serum albumin, vitamin D, C-reactive protein, and anti-transglutaminase autoantibodies |
US20220243178A1 (en) | 2019-05-31 | 2022-08-04 | The Broad Institute, Inc. | Methods for treating metabolic disorders by targeting adcy5 |
AR119264A1 (en) | 2019-06-05 | 2021-12-09 | Genentech Inc | METHOD FOR REUSE OF CHROMATOGRAPHY |
EP3980779A1 (en) | 2019-06-06 | 2022-04-13 | ProciseDx Inc. | Detection of hemoglobin a1c (hba1c) in blood |
KR20220031616A (en) | 2019-06-11 | 2022-03-11 | 알렉터 엘엘씨 | Anti-Sortilin Antibodies for Use in Therapy |
UY38747A (en) | 2019-06-12 | 2021-01-29 | Novartis Ag | NATRIURETIC 1 PEPTIDE RECEPTOR ANTIBODIES AND METHODS OF USE |
CA3144324A1 (en) | 2019-06-24 | 2020-12-30 | Novartis Ag | Dosing regimen and combination therapies for multispecific antibodies targeting b-cell maturation antigen |
JP2022540764A (en) | 2019-06-25 | 2022-09-20 | プロサイセデクス インコーポレイティド | Detection of anti-TNFα biologics and anti-drug antibodies |
WO2020264300A1 (en) | 2019-06-28 | 2020-12-30 | Genentech, Inc. | Composition and methods for stabilizing liquid protein formulations |
EP3996816A1 (en) | 2019-07-08 | 2022-05-18 | Imcare Biotech, LLC | Anti-serine protease inhibitor kazal (spik) antibodies, immunoconjugates, and methods of use |
WO2021005232A1 (en) | 2019-07-11 | 2021-01-14 | Umc Utrecht Holding B.V. | Intranasal administration of neutralising antiviral antibodies |
JPWO2021010326A1 (en) | 2019-07-12 | 2021-01-21 | ||
AU2020315878A1 (en) | 2019-07-19 | 2022-03-03 | Oncoresponse, Inc. | Immunomodulatory antibodies and methods of use thereof |
CN114787373A (en) | 2019-07-25 | 2022-07-22 | 免疫苏醒公司 | Method of measuring cell-mediated killing by effectors |
CN112300279A (en) | 2019-07-26 | 2021-02-02 | 上海复宏汉霖生物技术股份有限公司 | Methods and compositions directed to anti-CD 73 antibodies and variants |
KR20220058540A (en) | 2019-07-31 | 2022-05-09 | 알렉터 엘엘씨 | Anti-MS4A4A antibodies and methods of use thereof |
GB201911210D0 (en) | 2019-08-06 | 2019-09-18 | Amlo Biosciences Ltd | Clinical management of oropharyngeal squamous cell carcinoma |
JP7284256B2 (en) | 2019-08-12 | 2023-05-30 | ビオンド バイオロジクス リミテッド | Antibodies against ILT2 and uses thereof |
US20220282333A1 (en) | 2019-08-13 | 2022-09-08 | The General Hospital Corporation | Methods for predicting outcomes of checkpoint inhibition and treatment thereof |
TW202124439A (en) | 2019-09-04 | 2021-07-01 | 美商建南德克公司 | Cd8 binding agents and uses thereof |
JP2022547168A (en) | 2019-09-09 | 2022-11-10 | スクライブ・セラピューティクス・インコーポレイテッド | Compositions and methods for use in immunotherapy |
US20240043512A1 (en) | 2019-09-11 | 2024-02-08 | Imcare Biotech, Llc | Epitopes of anti-serine protease inhibitor kazal (spik) antibodies |
TW202118512A (en) | 2019-09-12 | 2021-05-16 | 美商建南德克公司 | Compositions and methods of treating lupus nephritis |
BR112022004674A2 (en) | 2019-09-17 | 2022-06-07 | Merck Patent Gmbh | Camphorsulfonic acid and combinations thereof with cationic excipients as viscosity reducing agents in highly concentrated protein formulations |
US20220348687A1 (en) | 2019-09-20 | 2022-11-03 | Genentech, Inc. | Dosing for anti-tryptase antibodies |
JP2022548978A (en) | 2019-09-27 | 2022-11-22 | ジェネンテック, インコーポレイテッド | Dosing for Treatment with Drugs Anti-TIGIT and Anti-PD-L1 Antagonist Antibodies |
EP4034560A1 (en) | 2019-09-27 | 2022-08-03 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Anti-müllerian inhibiting substance antibodies and uses thereof |
WO2021058729A1 (en) | 2019-09-27 | 2021-04-01 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Anti-müllerian inhibiting substance type i receptor antibodies and uses thereof |
GB201914399D0 (en) | 2019-10-04 | 2019-11-20 | Univ Newcastle | Biomarkers for assessing explant organ viability |
US11793787B2 (en) | 2019-10-07 | 2023-10-24 | The Broad Institute, Inc. | Methods and compositions for enhancing anti-tumor immunity by targeting steroidogenesis |
AU2020376305A1 (en) | 2019-10-31 | 2022-05-12 | Incyte Corporation | Anti-CD19 therapy in combination with lenalidomide for the treatment of leukemia or lymphoma |
CN115151565A (en) | 2019-10-31 | 2022-10-04 | 莫佛塞斯公司 | Anti-tumor combination therapy comprising anti-CD 19 antibody and gamma delta T cells |
CA3154413A1 (en) | 2019-11-01 | 2021-05-06 | Yan Lan | Combined inhibition of pd-1, tgf.beta. and atm together with radiotherapy for the treatment of cancer |
BR112022004998A2 (en) | 2019-11-05 | 2022-06-14 | Merck Patent Gmbh | Anti-Tigit antibodies and uses thereof |
BR112022008295A2 (en) | 2019-11-05 | 2022-07-26 | Merck Patent Gmbh | COMBINED INHIBITION OF PD-1, TGFBETA AND TIGIT FOR THE TREATMENT OF CANCER |
MX2022005400A (en) | 2019-11-06 | 2022-05-24 | Genentech Inc | Diagnostic and therapeutic methods for treatment of hematologic cancers. |
KR20220110537A (en) | 2019-12-05 | 2022-08-08 | 알렉터 엘엘씨 | How to Use Anti-TREM2 Antibodies |
WO2021116789A1 (en) | 2019-12-09 | 2021-06-17 | Novartis Ag | Anti-interleukin 1 beta antibodies for treatment of sickle cell disease |
WO2021116119A1 (en) | 2019-12-09 | 2021-06-17 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Antibodies having specificity to her4 and uses thereof |
WO2021116277A1 (en) | 2019-12-10 | 2021-06-17 | Institut Pasteur | New antibody blocking human fcgriiia and fcgriiib |
EP4073119A1 (en) | 2019-12-12 | 2022-10-19 | Alector LLC | Methods of use of anti-cd33 antibodies |
CR20220329A (en) | 2019-12-13 | 2022-11-23 | Alector Llc | Anti-mertk antibodies and methods of use thereof |
US11865168B2 (en) | 2019-12-30 | 2024-01-09 | Massachusetts Institute Of Technology | Compositions and methods for treating bacterial infections |
TW202142230A (en) | 2020-01-27 | 2021-11-16 | 美商建南德克公司 | Methods for treatment of cancer with an anti-tigit antagonist antibody |
WO2022050954A1 (en) | 2020-09-04 | 2022-03-10 | Genentech, Inc. | Dosing for treatment with anti-tigit and anti-pd-l1 antagonist antibodies |
WO2021194481A1 (en) | 2020-03-24 | 2021-09-30 | Genentech, Inc. | Dosing for treatment with anti-tigit and anti-pd-l1 antagonist antibodies |
WO2021151974A1 (en) | 2020-01-28 | 2021-08-05 | Stichting Het Nederlands Kanker Instituut - Antoni Van Leeuwenhoek Ziekenhuis | Interfering with mrna splicing to enhance response to checkpoint immunotherapies. |
TW202140550A (en) | 2020-01-29 | 2021-11-01 | 瑞士商諾華公司 | Methods of treating an inflammatory or obstructive airway disease using anti-tslp antibody |
CN116650628A (en) | 2020-01-31 | 2023-08-29 | 基因泰克公司 | Method for inducing neoepitope specific T cells with PD-1 axis binding antagonists and RNA vaccines |
CN113248611A (en) | 2020-02-13 | 2021-08-13 | 湖南华康恒健生物技术有限公司 | anti-BCMA antibody, pharmaceutical composition and application thereof |
EP4106767A1 (en) | 2020-02-21 | 2022-12-28 | Université de Liège | Depletion of ext1 expression and/or activity improves cellular production of biological entities |
JP2023515423A (en) | 2020-02-21 | 2023-04-13 | 江蘇恒瑞医薬股▲ふん▼有限公司 | ANTI-IL-4R ANTIBODY PHARMACEUTICAL COMPOSITION AND USE THEREOF |
US20230159637A1 (en) | 2020-02-24 | 2023-05-25 | Alector Llc | Methods of use of anti-trem2 antibodies |
EP4114854A1 (en) | 2020-03-05 | 2023-01-11 | UMC Utrecht Holding B.V. | Membrane ubiquitin ligases to target protein degradation |
WO2021255280A1 (en) | 2020-06-18 | 2021-12-23 | Umc Utrecht Holding B.V. | Screening method for effective target - e3 ligase combinations |
CR20220461A (en) | 2020-03-13 | 2022-10-21 | Genentech Inc | Anti-interleukin-33 antibodies and uses thereof |
WO2021195513A1 (en) | 2020-03-27 | 2021-09-30 | Novartis Ag | Bispecific combination therapy for treating proliferative diseases and autoimmune disorders |
CN116075525A (en) | 2020-03-31 | 2023-05-05 | 艾莱克特有限责任公司 | anti-MERTK antibodies and methods of use thereof |
MX2022012182A (en) | 2020-04-03 | 2022-12-08 | Alector Llc | Methods of use of anti-trem2 antibodies. |
BR112022020232A2 (en) | 2020-04-06 | 2022-12-13 | Yissum Res Dev Co Of Hebrew Univ Jerusalem Ltd | NKP46 ANTIBODIES AND CONSTRUCTS THEREOF FOR THE TREATMENT OF CANCER AND INFECTIONS |
BR112022017215A2 (en) | 2020-04-09 | 2022-10-18 | Univ Muenchen Tech | Targeted delivery of a MIR-21 inhibitor to macrophages for the treatment of pulmonary fibrosis |
WO2021209458A1 (en) | 2020-04-14 | 2021-10-21 | Ares Trading S.A. | Combination treatment of cancer |
US20230149360A1 (en) | 2020-04-21 | 2023-05-18 | Université Catholique de Louvain | Alpha-2 adrenergic receptor agonists for the prevention and/or the treatment of spleen disorders |
WO2021214129A1 (en) | 2020-04-21 | 2021-10-28 | Université Catholique de Louvain | Alpha-2 adrenergic receptor agonists for the treatment of cancer |
CN116368221A (en) | 2020-04-22 | 2023-06-30 | 因达普塔治疗公司 | Natural Killer (NK) cell compositions and methods of producing the same |
WO2021214258A1 (en) | 2020-04-22 | 2021-10-28 | Fabmid | Methods for circularizing linear double stranded nucleic acids |
JP2023523145A (en) | 2020-04-27 | 2023-06-02 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | Isotype-independent antibody against lipoprotein (a) |
WO2021222533A1 (en) | 2020-04-30 | 2021-11-04 | Procisedx Inc. | Methods of detecting antibodies to sars-cov-2 |
US20230181756A1 (en) | 2020-04-30 | 2023-06-15 | Novartis Ag | Ccr7 antibody drug conjugates for treating cancer |
IL297980A (en) | 2020-05-08 | 2023-01-01 | Alpine Immune Sciences Inc | April and baff inhibitory immunomodulatory proteins and methods of use thereof |
WO2021228956A1 (en) | 2020-05-12 | 2021-11-18 | INSERM (Institut National de la Santé et de la Recherche Médicale) | New method to treat cutaneous t-cell lymphomas and tfh derived lymphomas |
GB202007312D0 (en) | 2020-05-18 | 2020-07-01 | Synthetic Vac Ltd | Mimotope peptides of the spike protein from the sars-cov-2 virus |
KR20230014719A (en) | 2020-05-22 | 2023-01-30 | 추가이 세이야쿠 가부시키가이샤 | Antibodies that neutralize substances with coagulation factor VIII (F.VIII) alternative activity |
GB202008651D0 (en) | 2020-06-09 | 2020-07-22 | Univ Newcastle | Method of identifying complement modulators |
KR20230025691A (en) | 2020-06-16 | 2023-02-22 | 제넨테크, 인크. | Methods and compositions for treating triple negative breast cancer |
WO2021257124A1 (en) | 2020-06-18 | 2021-12-23 | Genentech, Inc. | Treatment with anti-tigit antibodies and pd-1 axis binding antagonists |
CN115956088A (en) | 2020-06-22 | 2023-04-11 | 莫佛塞斯公司 | Anti-tumor combination therapy comprising an anti-CD 19 antibody and a polypeptide that blocks a SIRPa-CD 47 innate immune checkpoint |
CN113912706A (en) | 2020-07-09 | 2022-01-11 | 北京凯因科技股份有限公司 | Antibody binding to hepatitis B virus surface antigen and application thereof |
EP4182025A1 (en) | 2020-07-16 | 2023-05-24 | Novartis AG | Anti-betacellulin antibodies, fragments thereof, and multi-specific binding molecules |
US20230293512A1 (en) | 2020-07-23 | 2023-09-21 | Erasmus University Medical Center Rotterdam | S100 proteins as novel therapeutic targets in myeloproliferative neoplasms |
FR3112939B1 (en) | 2020-07-31 | 2024-01-05 | Univ Montpellier | Universal cell therapy product and its use |
JP2023536602A (en) | 2020-08-03 | 2023-08-28 | ジェネンテック, インコーポレイテッド | Diagnostic and therapeutic methods for lymphoma |
WO2022035793A1 (en) | 2020-08-10 | 2022-02-17 | Precision Biosciences, Inc. | Antibodies and fragments specific for b-cell maturation antigen and uses thereof |
MX2023001776A (en) | 2020-08-12 | 2023-03-10 | Biond Biologics Ltd | Antibodies against ilt2 and use thereof. |
WO2022044010A1 (en) | 2020-08-26 | 2022-03-03 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. | Anti-t-cell immunoglobulin and itim domain (tigit) antibodies for the treatment of fungal infections |
CN114106173A (en) | 2020-08-26 | 2022-03-01 | 上海泰槿生物技术有限公司 | anti-OX 40 antibodies, pharmaceutical compositions and uses thereof |
BR112023004415A2 (en) | 2020-09-11 | 2023-05-09 | Medimmune Ltd | B7-H4 BINDING THERAPEUTIC MOLECULES |
FR3114160A1 (en) | 2020-09-11 | 2022-03-18 | Dyameo | FLUORESCENT REPORTER AND ITS USE FOR THE DETECTION OF TARGET MOLECULES |
EP4211663A2 (en) | 2020-09-12 | 2023-07-19 | MedImmune Limited | A scoring method for an anti-b7h4 antibody-drug conjugate therapy |
AU2021342566A1 (en) | 2020-09-21 | 2023-03-02 | Genentech, Inc. | Purification of multispecific antibodies |
TW202228781A (en) | 2020-09-24 | 2022-08-01 | 美商建南德克公司 | Polysorbate mixtures having modified fatty acid ester distribution |
WO2022063819A1 (en) | 2020-09-24 | 2022-03-31 | Morphosys Ag | Novel human antibodies binding to human cd3 epsilon |
WO2022084915A1 (en) | 2020-10-22 | 2022-04-28 | Janssen Biotech, Inc. | Proteins comprising delta-like ligand 3 (dll3) antigen binding domains and their uses |
WO2022093981A1 (en) | 2020-10-28 | 2022-05-05 | Genentech, Inc. | Combination therapy comprising ptpn22 inhibitors and pd-l1 binding antagonists |
EP4237001A1 (en) | 2020-11-02 | 2023-09-06 | Ares Trading S.A. | Combination treatment of cancer |
WO2022090529A1 (en) | 2020-11-02 | 2022-05-05 | Ares Trading S.A. | Combination treatment of cancer |
EP4240367A2 (en) | 2020-11-04 | 2023-09-13 | Myeloid Therapeutics, Inc. | Engineered chimeric fusion protein compositions and methods of use thereof |
WO2022097090A1 (en) | 2020-11-05 | 2022-05-12 | Novartis Ag | Dosing regimen for combination therapies with multispecific antibodies targeting b-cell maturation antigen and gamma secretase inhibitors |
EP4240491A1 (en) | 2020-11-06 | 2023-09-13 | Novartis AG | Cd19 binding molecules and uses thereof |
JP2023547499A (en) | 2020-11-06 | 2023-11-10 | ノバルティス アーゲー | Antibody Fc variant |
MX2023005234A (en) | 2020-11-06 | 2023-05-18 | Novartis Ag | Anti-cd19 agent and b cell targeting agent combination therapy for treating b cell malignancies. |
AU2021376218A1 (en) | 2020-11-08 | 2023-06-15 | Seagen Inc. | Combination Therapy |
MX2023006010A (en) | 2020-11-24 | 2023-06-08 | Novartis Ag | Anti-cd48 antibodies, antibody drug conjugates, and uses thereof. |
US20240101681A1 (en) | 2020-12-02 | 2024-03-28 | Alector Llc | Methods of use of anti-sortilin antibodies |
IL303384A (en) | 2020-12-04 | 2023-08-01 | Morphosys Ag | Anti-cd19 combination therapy |
CN116802211A (en) | 2020-12-07 | 2023-09-22 | Ucb生物制药有限责任公司 | Antibodies against interleukin-22 |
US20240067758A1 (en) | 2020-12-07 | 2024-02-29 | UCB Biopharma SRL | Multi-specific antibodies and antibody combinations |
WO2022125710A1 (en) | 2020-12-09 | 2022-06-16 | GHP Solutions, LLC | Methods of detecting papp-a and related methods for gestational age assessment |
WO2022130182A1 (en) | 2020-12-14 | 2022-06-23 | Novartis Ag | Reversal binding agents for anti-natriuretic peptide receptor 1 (npr1) antibodies and uses thereof |
WO2022140797A1 (en) | 2020-12-23 | 2022-06-30 | Immunowake Inc. | Immunocytokines and uses thereof |
JP2024503724A (en) | 2021-01-20 | 2024-01-26 | オンコレスポンス,インク. | Immunomodulatory antibodies and their uses |
EP4291580A1 (en) | 2021-02-11 | 2023-12-20 | Nectin Therapeutics Ltd. | Antibodies against cd112r and uses thereof |
JP2024508488A (en) | 2021-03-01 | 2024-02-27 | エクシリオ デベロップメント, インコーポレイテッド | Combination of masked CTLA4 and PD1/PD-L1 antibodies to treat cancer |
US20220306743A1 (en) | 2021-03-01 | 2022-09-29 | Xilio Development, Inc. | Combination of ctla4 and pd1/pdl1 antibodies for treating cancer |
EP4301776A1 (en) | 2021-03-04 | 2024-01-10 | Centre National de la Recherche Scientifique (CNRS) | Use of a periostin antibody for treating inflammation, fibrosis and lung diseases |
IL305758A (en) | 2021-03-10 | 2023-11-01 | Immunowake Inc | Immunomodulatory molecules and uses thereof |
WO2022198192A1 (en) | 2021-03-15 | 2022-09-22 | Genentech, Inc. | Compositions and methods of treating lupus nephritis |
JP2024512002A (en) | 2021-03-18 | 2024-03-18 | アレクトル エルエルシー | Anti-TMEM106B antibody and method of use thereof |
CA3212630A1 (en) | 2021-03-18 | 2022-09-22 | Medimmune Limited | Therapeutic binding molecules |
WO2022204274A1 (en) | 2021-03-23 | 2022-09-29 | Alector Llc | Anti-tmem106b antibodies for treating and preventing coronavirus infections |
KR20230162793A (en) | 2021-03-26 | 2023-11-28 | 얀센 바이오테크 인코포레이티드 | Humanized antibodies against paired helical filament tau and uses thereof |
WO2022217026A1 (en) | 2021-04-09 | 2022-10-13 | Seagen Inc. | Methods of treating cancer with anti-tigit antibodies |
WO2022221720A1 (en) | 2021-04-16 | 2022-10-20 | Novartis Ag | Antibody drug conjugates and methods for making thereof |
AU2022262606A1 (en) | 2021-04-21 | 2023-11-09 | Indapta Therapeutics, Inc. | Methods of treatment and dosing of natural killer cell compositions |
AR125732A1 (en) | 2021-05-03 | 2023-08-09 | UCB Biopharma SRL | ANTI-TREM1 ANTIBODIES |
EP4333900A2 (en) | 2021-05-03 | 2024-03-13 | Merck Patent GmbH | Her2 targeting fc antigen binding fragment-drug conjugates |
IL308336A (en) | 2021-05-07 | 2024-01-01 | Alpine Immune Sciences Inc | Methods of dosing and treatment with a taci-fc fusion immunomodulatory protein |
EP4337689A1 (en) | 2021-05-12 | 2024-03-20 | Applied Biomedical Science Institute | Binding polypeptides against sars cov-2 and uses thereof |
CN115368473A (en) | 2021-05-19 | 2022-11-22 | 上海诗健生物科技有限公司 | Chimeric antigen receptor molecule for specifically recognizing BAFF-R and application thereof |
AU2022280341A1 (en) | 2021-05-25 | 2024-01-04 | Merck Patent Gmbh | Egfr targeting fc antigen binding fragment-drug conjugates |
WO2022258622A1 (en) | 2021-06-07 | 2022-12-15 | Ares Trading S.A. | Combination treatment of cancer |
EP4355783A1 (en) | 2021-06-16 | 2024-04-24 | Alector LLC | Monovalent anti-mertk antibodies and methods of use thereof |
CN117642426A (en) | 2021-06-16 | 2024-03-01 | 艾莱克特有限责任公司 | Bispecific anti-MerTK and anti-PDL 1 antibodies and methods of use thereof |
EP4355352A1 (en) | 2021-06-18 | 2024-04-24 | advanceCOR GmbH | Use of a pharmaceutical composition |
AU2022301302A1 (en) | 2021-07-01 | 2024-01-25 | Indapta Therapeutics, Inc. | Engineered natural killer (nk) cells and related methods |
CA3227537A1 (en) | 2021-07-27 | 2023-02-02 | Morphosys Ag | Combinations of antigen binding molecules |
WO2023006919A1 (en) | 2021-07-29 | 2023-02-02 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | HUMANIZED ANTI-HUMAN βIG-H3 PROTEIN AND USES THEREOF |
WO2023019239A1 (en) | 2021-08-13 | 2023-02-16 | Genentech, Inc. | Dosing for anti-tryptase antibodies |
TW202328170A (en) | 2021-09-14 | 2023-07-16 | 美商艾希利歐發展股份有限公司 | Cleavable linkers |
WO2023064872A1 (en) | 2021-10-14 | 2023-04-20 | Precision Biosciences, Inc. | Combinations of anti-bcma car t cells and gamma secretase inhibitors |
CA3234162A1 (en) | 2021-10-15 | 2023-04-20 | Michele Fiscella | Antibodies and methods of using thereof |
WO2023069919A1 (en) | 2021-10-19 | 2023-04-27 | Alector Llc | Anti-cd300lb antibodies and methods of use thereof |
WO2023072958A1 (en) | 2021-10-25 | 2023-05-04 | Fabmid | Methods for circularizing linear double stranded nucleic acids and the products thereof |
TW202325345A (en) | 2021-10-27 | 2023-07-01 | 美商建南德克公司 | Synthesis of restrained complexing agents |
WO2023072916A1 (en) | 2021-10-27 | 2023-05-04 | Granite Bio Ag | Antibodies targeting ccr2 |
WO2023081898A1 (en) | 2021-11-08 | 2023-05-11 | Alector Llc | Soluble cd33 as a biomarker for anti-cd33 efficacy |
WO2023086807A1 (en) | 2021-11-10 | 2023-05-19 | Genentech, Inc. | Anti-interleukin-33 antibodies and uses thereof |
WO2023105528A1 (en) | 2021-12-12 | 2023-06-15 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. | Antibodies specific to ceacam1 |
WO2023117987A1 (en) | 2021-12-21 | 2023-06-29 | Universität Zürich | Adenoviral vectors |
WO2023122665A1 (en) | 2021-12-22 | 2023-06-29 | Genentech, Inc. | Clinical formulations of anti-tigit antibodies |
WO2023122796A1 (en) | 2021-12-23 | 2023-06-29 | The Broad Institute, Inc. | Parallel antibody engineering compositions and methods |
WO2023148707A1 (en) | 2022-02-07 | 2023-08-10 | Yeda Research And Development Co. Ltd. | Humanized anti quiescin suefhydrye oxidase 1 (qsox1) antibodies and uses thereof |
TW202348252A (en) | 2022-02-16 | 2023-12-16 | 英商梅迪繆思有限公司 | Combination therapies for treatment of cancer with therapeutic binding molecules |
WO2023156625A1 (en) | 2022-02-18 | 2023-08-24 | Adivo Gmbh | Feline antibody library |
WO2023164516A1 (en) | 2022-02-23 | 2023-08-31 | Alector Llc | Methods of use of anti-trem2 antibodies |
GB202202569D0 (en) | 2022-02-24 | 2022-04-13 | Amlo Biosciences Ltd | Biomarkers for disease progression and/or recurrence in squamous cell carcinoma |
US20230365641A1 (en) | 2022-02-28 | 2023-11-16 | Xilio Development, Inc. | Targeted cytokines and methods of use thereof |
WO2023164286A1 (en) | 2022-02-28 | 2023-08-31 | Xilio Development, Inc. | Engineered cd122 compositions and methods thereof |
WO2023169896A1 (en) | 2022-03-09 | 2023-09-14 | Astrazeneca Ab | BINDING MOLECULES AGAINST FRα |
TW202346355A (en) | 2022-03-11 | 2023-12-01 | 比利時商健生藥品公司 | Multispecific antibodies and uses thereof |
WO2023170296A1 (en) | 2022-03-11 | 2023-09-14 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | Nucleic acid system to specifically reprogram b and t cells and uses thereof |
WO2023170291A1 (en) | 2022-03-11 | 2023-09-14 | Janssen Pharmaceutica Nv | Multispecific antibodies and uses thereof |
WO2023170216A1 (en) | 2022-03-11 | 2023-09-14 | Astrazeneca Ab | A SCORING METHOD FOR AN ANTI-FRα ANTIBODY-DRUG CONJUGATE THERAPY |
WO2023170295A1 (en) | 2022-03-11 | 2023-09-14 | Janssen Pharmaceutica Nv | Multispecific antibodies and uses thereof |
WO2023175171A1 (en) | 2022-03-18 | 2023-09-21 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | Bk polyomavirus antibodies and uses thereof |
WO2023180346A1 (en) | 2022-03-22 | 2023-09-28 | Morphosys Ag | Deimmunized antibodies specific for cd3 |
WO2023180527A1 (en) | 2022-03-25 | 2023-09-28 | Universität Zürich | Adenoviral mediated targeting of activated immune cells |
WO2023187657A1 (en) | 2022-03-30 | 2023-10-05 | Novartis Ag | Methods of treating disorders using anti-natriuretic peptide receptor 1 (npr1) antibodies |
US20230364020A1 (en) | 2022-04-01 | 2023-11-16 | Genentech, Inc. | Hydroxypropyl methyl cellulose derivatives to stabilize polypeptides |
TW202340259A (en) | 2022-04-14 | 2023-10-16 | 瑞士商諾華公司 | Dosage regimens for anti-cd19 agents and uses thereof |
WO2023209716A1 (en) | 2022-04-25 | 2023-11-02 | Biond Biologics Ltd. | Anti-ilt3 antibodies and use thereof |
EP4269432A1 (en) | 2022-04-26 | 2023-11-01 | Universite de Rouen Normandie | Production of therapeutic antibodies by the microalgae phaeodactylum tricornutum |
TW202400658A (en) | 2022-04-26 | 2024-01-01 | 瑞士商諾華公司 | Multispecific antibodies targeting il-13 and il-18 |
WO2023240058A2 (en) | 2022-06-07 | 2023-12-14 | Genentech, Inc. | Prognostic and therapeutic methods for cancer |
WO2024007020A1 (en) | 2022-06-30 | 2024-01-04 | Indapta Therapeutics, Inc. | Combination of engineered natural killer (nk) cells and antibody therapy and related methods |
WO2024008910A1 (en) | 2022-07-07 | 2024-01-11 | Cimeio Therapeutics Ag | Antibodies targeting cd117 |
WO2024016003A2 (en) | 2022-07-14 | 2024-01-18 | The Broad Institute, Inc. | Aav capsids that enable cns-wide gene delivery through interactions with the transferrin receptor |
WO2024015960A1 (en) | 2022-07-15 | 2024-01-18 | Xilio Development, Inc. | Engineered cleavable fc domain as carriers and methods of use thereof |
WO2024026447A1 (en) | 2022-07-29 | 2024-02-01 | Alector Llc | Anti-gpnmb antibodies and methods of use thereof |
US20240092859A1 (en) | 2022-08-18 | 2024-03-21 | Immunocore Ltd | T cell receptors and fusion proteins thereof |
WO2024047114A1 (en) | 2022-08-31 | 2024-03-07 | Universität Zürich | Adenoviral-based in situ delivery of bispecific t cell engagers |
WO2024052503A1 (en) | 2022-09-08 | 2024-03-14 | Institut National de la Santé et de la Recherche Médicale | Antibodies having specificity to ltbp2 and uses thereof |
WO2024056668A1 (en) | 2022-09-12 | 2024-03-21 | Institut National de la Santé et de la Recherche Médicale | New anti-itgb8 antibodies and its uses thereof |
WO2024077018A2 (en) | 2022-10-04 | 2024-04-11 | Alpine Immune Sciences, Inc. | Methods and uses of taci-fc fusion immunomodulatory protein |
WO2024074649A1 (en) | 2022-10-05 | 2024-04-11 | Alcea Therapeutics, Inc. | Notch4 antibodies, compositions, and methods for treating airway inflammation |
WO2024074706A1 (en) | 2022-10-07 | 2024-04-11 | Universität Zürich | Paracrine adenoviral delivery of biomolecules |
WO2024077256A1 (en) | 2022-10-07 | 2024-04-11 | The General Hospital Corporation | Methods and compositions for high-throughput discovery ofpeptide-mhc targeting binding proteins |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1992012993A1 (en) * | 1991-01-16 | 1992-08-06 | The Salk Institute Biotechnology/Industrial Associates, Inc. | Method for the purificatioin of intact, correctly-folded insulin-like growth factor-1 |
WO1992022653A1 (en) * | 1991-06-14 | 1992-12-23 | Genentech, Inc. | Method for making humanized antibodies |
US5429746A (en) * | 1994-02-22 | 1995-07-04 | Smith Kline Beecham Corporation | Antibody purification |
Family Cites Families (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4000098A (en) * | 1974-08-16 | 1976-12-28 | Palo Alto Medical Research Foundation | Separation of proteins by hydrophobic adsorption |
US5618920A (en) * | 1985-11-01 | 1997-04-08 | Xoma Corporation | Modular assembly of antibody genes, antibodies prepared thereby and use |
WO1989006692A1 (en) * | 1988-01-12 | 1989-07-27 | Genentech, Inc. | Method of treating tumor cells by inhibiting growth factor receptor function |
US5851527A (en) * | 1988-04-18 | 1998-12-22 | Immunomedics, Inc. | Method for antibody targeting of therapeutic agents |
DE3920358A1 (en) | 1989-06-22 | 1991-01-17 | Behringwerke Ag | BISPECIFIC AND OLIGO-SPECIFIC, MONO- AND OLIGOVALENT ANTI-BODY CONSTRUCTS, THEIR PRODUCTION AND USE |
DE4118120A1 (en) | 1991-06-03 | 1992-12-10 | Behringwerke Ag | TETRAVALENT BISPECIFIC RECEPTORS, THEIR PRODUCTION AND USE |
WO1994004679A1 (en) * | 1991-06-14 | 1994-03-03 | Genentech, Inc. | Method for making humanized antibodies |
US7018809B1 (en) * | 1991-09-19 | 2006-03-28 | Genentech, Inc. | Expression of functional antibody fragments |
CA2122732C (en) * | 1991-11-25 | 2008-04-08 | Marc D. Whitlow | Multivalent antigen-binding proteins |
JP3720353B2 (en) * | 1992-12-04 | 2005-11-24 | メディカル リサーチ カウンシル | Multivalent and multispecific binding proteins, their production and use |
ATE187494T1 (en) | 1992-12-11 | 1999-12-15 | Dow Chemical Co | MULTIVALENT SINGLE CHAIN ANTIBODIES |
GB9412166D0 (en) | 1993-09-22 | 1994-08-10 | Medical Res Council | Retargetting antibodies |
US5641870A (en) * | 1995-04-20 | 1997-06-24 | Genentech, Inc. | Low pH hydrophobic interaction chromatography for antibody purification |
US5747035A (en) * | 1995-04-14 | 1998-05-05 | Genentech, Inc. | Polypeptides with increased half-life for use in treating disorders involving the LFA-1 receptor |
US5989830A (en) * | 1995-10-16 | 1999-11-23 | Unilever Patent Holdings Bv | Bifunctional or bivalent antibody fragment analogue |
-
1995
- 1995-04-20 US US08/425,763 patent/US5641870A/en not_active Expired - Lifetime
-
1996
- 1996-04-05 MX MX9707909A patent/MX9707909A/en unknown
- 1996-04-05 EP EP06022818A patent/EP1752465B1/en not_active Expired - Lifetime
- 1996-04-05 AT AT96912575T patent/ATE346858T1/en active
- 1996-04-05 AU AU55349/96A patent/AU721736B2/en not_active Expired
- 1996-04-05 JP JP53177496A patent/JP4042868B2/en not_active Expired - Lifetime
- 1996-04-05 AT AT06022818T patent/ATE510854T1/en active
- 1996-04-05 DK DK06022818.6T patent/DK1752465T3/en active
- 1996-04-05 ES ES06022818T patent/ES2365929T3/en not_active Expired - Lifetime
- 1996-04-05 CA CA002214633A patent/CA2214633C/en not_active Expired - Lifetime
- 1996-04-05 ES ES96912575T patent/ES2277344T3/en not_active Expired - Lifetime
- 1996-04-05 WO PCT/US1996/004683 patent/WO1996033208A1/en active IP Right Grant
- 1996-04-05 DE DE69636733T patent/DE69636733T2/en not_active Expired - Lifetime
- 1996-04-05 PT PT96912575T patent/PT821695E/en unknown
- 1996-04-05 EP EP96912575A patent/EP0821695B1/en not_active Expired - Lifetime
- 1996-04-05 DK DK96912575T patent/DK0821695T3/en active
- 1996-04-05 NZ NZ306718A patent/NZ306718A/en not_active IP Right Cessation
- 1996-04-11 ZA ZA9602885A patent/ZA962885B/en unknown
- 1996-04-17 IL IL11794296A patent/IL117942A/en not_active IP Right Cessation
-
1997
- 1997-03-06 US US08/811,757 patent/US6066719A/en not_active Expired - Lifetime
-
1999
- 1999-02-11 US US09/249,230 patent/US6214984B1/en not_active Expired - Lifetime
- 1999-02-16 NZ NZ334211A patent/NZ334211A/en not_active IP Right Cessation
-
2001
- 2001-01-04 US US09/754,998 patent/US7038017B2/en not_active Expired - Fee Related
-
2005
- 2005-07-01 US US11/173,564 patent/US8012754B2/en not_active Expired - Fee Related
-
2006
- 2006-05-15 JP JP2006135061A patent/JP4153533B2/en not_active Expired - Lifetime
- 2006-05-15 JP JP2006135062A patent/JP4091087B2/en not_active Expired - Lifetime
-
2007
- 2007-04-25 HK HK07104405.4A patent/HK1099310A1/en not_active IP Right Cessation
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1992012993A1 (en) * | 1991-01-16 | 1992-08-06 | The Salk Institute Biotechnology/Industrial Associates, Inc. | Method for the purificatioin of intact, correctly-folded insulin-like growth factor-1 |
WO1992022653A1 (en) * | 1991-06-14 | 1992-12-23 | Genentech, Inc. | Method for making humanized antibodies |
US5429746A (en) * | 1994-02-22 | 1995-07-04 | Smith Kline Beecham Corporation | Antibody purification |
Non-Patent Citations (5)
Title |
---|
D. NEBLOCK ET AL.: "Conjugation and evaluation of 7E3xP4B6, a chemically cross-linked bispecific F(ab')2 antibody which inhibits platelet aggregation and localizes tissue plasminogen activator to the platelet surface.", BIOCONJUGATE CHEMISTRY, vol. 3, no. 2, January 1992 (1992-01-01), WASHINGTON, DC, USA, pages 126 - 131, XP002010285 * |
D. REA ET AL.: "The rapid development of hydrophobic interaction chromatography purification of a murine monoclonal IgG2a F(ab')2 fragment.", JOURNAL OF CELLULAR BIOCHEMISTRY, SUPPLEMENT, vol. 0, no. 17 part A, 1993, NEW YORK, NY, USA, pages 50, XP000578103 * |
G. KURZBAN ET AL.: "Purification of bovine liver rhodanese by low-pH column chromatography.", PROTEIN EXPRESSION AND PURIFICATION, vol. 2, no. 5-6, October 1991 (1991-10-01), SAN DIEGO, CA, USA, pages 379 - 384, XP000578101 * |
H. ALFTHAN ET AL.: "Purification of labelled antibodies by hydrophobic interaction chromatography.", JOURNAL OF CHROMATOGRAPHY, vol. 470, no. 2, 26 May 1989 (1989-05-26), AMSTERDAM, THE NETHERLANDS, pages 385 - 389, XP000577281 * |
M. RODRIGUES ET AL.: "Development of a humanized disulfide-stabilized anti-p185HER2 Fv-beta-lactamase fusion protein for activation of a cephalosporin doxorubicin prodrug.", CANCER RESEARCH, vol. 55, no. 1, 1 January 1995 (1995-01-01), BALTIMORE, MD, USA, pages 63 - 70, XP002010284 * |
Cited By (85)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1308456A3 (en) * | 1998-05-06 | 2003-05-14 | Genentech, Inc. | Antibody purification by ion exchange chromatography |
US6339142B1 (en) | 1998-05-06 | 2002-01-15 | Genentech, Inc. | Protein purification |
US7531645B2 (en) | 1998-05-06 | 2009-05-12 | Genentech, Inc. | Protein purification |
AU2003200708B2 (en) * | 1998-05-06 | 2007-01-04 | Genentech, Inc. | Protein purification |
US6489447B1 (en) | 1998-05-06 | 2002-12-03 | Genentech, Inc. | Protein purification |
EP1308456A2 (en) * | 1998-05-06 | 2003-05-07 | Genentech, Inc. | Antibody purification by ion exchange chromatography |
EP1308455A2 (en) * | 1998-05-06 | 2003-05-07 | Genentech, Inc. | A composition comprising anti-HER2 antibodies |
EP1308455A3 (en) * | 1998-05-06 | 2003-05-14 | Genentech, Inc. | A composition comprising anti-HER2 antibodies |
US9249218B2 (en) | 1998-05-06 | 2016-02-02 | Genentech, Inc. | Protein purification |
CN103641885A (en) * | 1998-05-06 | 2014-03-19 | 基因技术股份有限公司 | Protein purification by ion exchange chromatography |
US6417335B1 (en) | 1998-05-06 | 2002-07-09 | Genentech, Inc. | Protein purification |
WO1999057134A1 (en) * | 1998-05-06 | 1999-11-11 | Genentech, Inc. | Protein purification by ion exchange chromatography |
US7074404B2 (en) | 1998-05-06 | 2006-07-11 | Genentech, Inc. | Protein purification |
WO2001064711A1 (en) * | 2000-03-02 | 2001-09-07 | Kyowa Hakko Kogyo Co., Ltd. | Method of separating and purifying protein |
US7064191B2 (en) | 2000-10-06 | 2006-06-20 | Kyowa Hakko Kogyo Co., Ltd. | Process for purifying antibody |
EP1333032A4 (en) * | 2000-10-06 | 2005-03-16 | Kyowa Hakko Kogyo Kk | Method of purifying antibody |
EP1333032A1 (en) * | 2000-10-06 | 2003-08-06 | Kyowa Hakko Kogyo Co., Ltd. | Method of purifying antibody |
WO2004087761A1 (en) * | 2003-03-31 | 2004-10-14 | Kirin Beer Kabushiki Kaisha | Purification of human monoclonal antibody and human polyclonal antibody |
AU2004285928B2 (en) * | 2003-10-24 | 2012-02-02 | Amgen, Inc. | Process for purifying proteins in a hydrophobic interaction chromatography flow-through fraction |
US7427659B2 (en) | 2003-10-24 | 2008-09-23 | Amgen Inc. | Process for purifying proteins in a hydrophobic interaction chromatography flow-through fraction |
EP1687328A1 (en) * | 2003-10-24 | 2006-08-09 | Amgen, Inc. | Process for purifying proteins in a hydrophobic interaction chromatography flow-through fraction |
EP1687328A4 (en) * | 2003-10-24 | 2006-11-15 | Amgen Inc | Process for purifying proteins in a hydrophobic interaction chromatography flow-through fraction |
US11083792B2 (en) | 2006-04-05 | 2021-08-10 | Abbvie Biotechnology Ltd | Purified antibody composition |
US9096666B2 (en) | 2006-04-05 | 2015-08-04 | Abbvie Biotechnology Ltd | Purified antibody composition |
US9273132B2 (en) | 2006-04-05 | 2016-03-01 | Abbvie Biotechnology Ltd | Purified antibody composition |
US7863426B2 (en) | 2006-04-05 | 2011-01-04 | Abbott Biotechnology Ltd. | Antibody purification |
US8883156B2 (en) | 2006-04-05 | 2014-11-11 | Abbvie Biotechnology Ltd. | Purified antibody composition |
US8895009B2 (en) | 2006-04-05 | 2014-11-25 | Abbvie Biotechnology Ltd. | Purified antibody composition |
US8906372B2 (en) | 2006-04-05 | 2014-12-09 | Abbvie Biotechnology Ltd. | Purified antibody composition |
US8916153B2 (en) | 2006-04-05 | 2014-12-23 | Abbvie Biotechnology Ltd. | Purified antibody composition |
US9328165B2 (en) | 2006-04-05 | 2016-05-03 | Abbvie Biotechnology Ltd. | Purified antibody composition |
EP2004689A4 (en) * | 2006-04-05 | 2010-06-02 | Abbott Biotech Ltd | Antibody purification |
US9102723B2 (en) | 2006-04-05 | 2015-08-11 | Abbvie Biotechnology Ltd | Purified antibody composition |
US8231876B2 (en) | 2006-04-05 | 2012-07-31 | Abbott Biotechnology Ltd. | Purified antibody composition |
US9913902B2 (en) | 2006-04-05 | 2018-03-13 | Abbvie Biotechnology Ltd. | Purified antibody composition |
US11248053B2 (en) | 2007-09-26 | 2022-02-15 | Chugai Seiyaku Kabushiki Kaisha | Method of modifying isoelectric point of antibody via amino acid substitution in CDR |
US9896478B2 (en) | 2007-10-30 | 2018-02-20 | Genentech, Inc. | Antibody purification by cation exchange chromatography |
EP3441402A1 (en) | 2007-10-30 | 2019-02-13 | Genentech, Inc. | Antibody purification by cation exchange chromatography |
EP2840090A1 (en) | 2007-10-30 | 2015-02-25 | Genentech, Inc. | Antibody purification by cation exchange chromatography |
EP2565206A2 (en) | 2007-10-30 | 2013-03-06 | Genentech, Inc. | Antibody purification by cation exchange chromatography |
EP2344532A1 (en) | 2008-10-06 | 2011-07-20 | MSD Biologics (UK) Limited | Purification process for fragment antibodies |
US9062106B2 (en) | 2011-04-27 | 2015-06-23 | Abbvie Inc. | Methods for controlling the galactosylation profile of recombinantly-expressed proteins |
US9090688B2 (en) | 2011-04-27 | 2015-07-28 | Abbvie Inc. | Methods for controlling the galactosylation profile of recombinantly-expressed proteins |
US9505834B2 (en) | 2011-04-27 | 2016-11-29 | Abbvie Inc. | Methods for controlling the galactosylation profile of recombinantly-expressed proteins |
US9365645B1 (en) | 2011-04-27 | 2016-06-14 | Abbvie, Inc. | Methods for controlling the galactosylation profile of recombinantly-expressed proteins |
US9255143B2 (en) | 2011-04-27 | 2016-02-09 | Abbvie Inc. | Methods for controlling the galactosylation profile of recombinantly-expressed proteins |
US9193787B2 (en) | 2012-04-20 | 2015-11-24 | Abbvie Inc. | Human antibodies that bind human TNF-alpha and methods of preparing the same |
US9346879B2 (en) | 2012-04-20 | 2016-05-24 | Abbvie Inc. | Protein purification methods to reduce acidic species |
US9150645B2 (en) | 2012-04-20 | 2015-10-06 | Abbvie, Inc. | Cell culture methods to reduce acidic species |
US9683033B2 (en) | 2012-04-20 | 2017-06-20 | Abbvie, Inc. | Cell culture methods to reduce acidic species |
US9957318B2 (en) | 2012-04-20 | 2018-05-01 | Abbvie Inc. | Protein purification methods to reduce acidic species |
US9359434B2 (en) | 2012-04-20 | 2016-06-07 | Abbvie, Inc. | Cell culture methods to reduce acidic species |
US9505833B2 (en) | 2012-04-20 | 2016-11-29 | Abbvie Inc. | Human antibodies that bind human TNF-alpha and methods of preparing the same |
US9708400B2 (en) | 2012-04-20 | 2017-07-18 | Abbvie, Inc. | Methods to modulate lysine variant distribution |
US9181572B2 (en) | 2012-04-20 | 2015-11-10 | Abbvie, Inc. | Methods to modulate lysine variant distribution |
US9334319B2 (en) | 2012-04-20 | 2016-05-10 | Abbvie Inc. | Low acidic species compositions |
US9249182B2 (en) | 2012-05-24 | 2016-02-02 | Abbvie, Inc. | Purification of antibodies using hydrophobic interaction chromatography |
US9290568B2 (en) | 2012-09-02 | 2016-03-22 | Abbvie, Inc. | Methods to control protein heterogeneity |
US9234033B2 (en) | 2012-09-02 | 2016-01-12 | Abbvie, Inc. | Methods to control protein heterogeneity |
US9512214B2 (en) | 2012-09-02 | 2016-12-06 | Abbvie, Inc. | Methods to control protein heterogeneity |
US9206390B2 (en) | 2012-09-02 | 2015-12-08 | Abbvie, Inc. | Methods to control protein heterogeneity |
US10023608B1 (en) | 2013-03-13 | 2018-07-17 | Amgen Inc. | Protein purification methods to remove impurities |
US9067990B2 (en) | 2013-03-14 | 2015-06-30 | Abbvie, Inc. | Protein purification using displacement chromatography |
US9499614B2 (en) | 2013-03-14 | 2016-11-22 | Abbvie Inc. | Methods for modulating protein glycosylation profiles of recombinant protein therapeutics using monosaccharides and oligosaccharides |
US8921526B2 (en) | 2013-03-14 | 2014-12-30 | Abbvie, Inc. | Mutated anti-TNFα antibodies and methods of their use |
US9708399B2 (en) | 2013-03-14 | 2017-07-18 | Abbvie, Inc. | Protein purification using displacement chromatography |
US9598667B2 (en) | 2013-10-04 | 2017-03-21 | Abbvie Inc. | Use of metal ions for modulation of protein glycosylation profiles of recombinant proteins |
US9085618B2 (en) | 2013-10-18 | 2015-07-21 | Abbvie, Inc. | Low acidic species compositions and methods for producing and using the same |
US9200069B2 (en) | 2013-10-18 | 2015-12-01 | Abbvie, Inc. | Low acidic species compositions and methods for producing and using the same |
US9181337B2 (en) | 2013-10-18 | 2015-11-10 | Abbvie, Inc. | Modulated lysine variant species compositions and methods for producing and using the same |
US9688752B2 (en) | 2013-10-18 | 2017-06-27 | Abbvie Inc. | Low acidic species compositions and methods for producing and using the same using displacement chromatography |
US9522953B2 (en) | 2013-10-18 | 2016-12-20 | Abbvie, Inc. | Low acidic species compositions and methods for producing and using the same |
US9315574B2 (en) | 2013-10-18 | 2016-04-19 | Abbvie, Inc. | Low acidic species compositions and methods for producing and using the same |
US9499616B2 (en) | 2013-10-18 | 2016-11-22 | Abbvie Inc. | Modulated lysine variant species compositions and methods for producing and using the same |
US9200070B2 (en) | 2013-10-18 | 2015-12-01 | Abbvie, Inc. | Low acidic species compositions and methods for producing and using the same |
US9266949B2 (en) | 2013-10-18 | 2016-02-23 | Abbvie, Inc. | Low acidic species compositions and methods for producing and using the same |
US8946395B1 (en) | 2013-10-18 | 2015-02-03 | Abbvie Inc. | Purification of proteins using hydrophobic interaction chromatography |
US9017687B1 (en) | 2013-10-18 | 2015-04-28 | Abbvie, Inc. | Low acidic species compositions and methods for producing and using the same using displacement chromatography |
US9550826B2 (en) | 2013-11-15 | 2017-01-24 | Abbvie Inc. | Glycoengineered binding protein compositions |
US11214623B2 (en) | 2014-09-26 | 2022-01-04 | Chugai Seiyaku Kabushiki Kaisha | Antibody capable of neutralizing substance having activity alternative to function of coagulation factor VIII (FVIII) |
US9526768B2 (en) | 2014-11-13 | 2016-12-27 | Jennifer Mai | Compositions for the treatment of cancer |
US11649262B2 (en) | 2015-12-28 | 2023-05-16 | Chugai Seiyaku Kabushiki Kaisha | Method for promoting efficiency of purification of Fc region-containing polypeptide |
US11352438B2 (en) | 2016-09-06 | 2022-06-07 | Chugai Seiyaku Kabushiki Kaisha | Methods of using a bispecific antibody that recognizes coagulation factor IX and/or activated coagulation factor IX and coagulation factor X and/or activated coagulation factor X |
CN111479829A (en) * | 2017-11-01 | 2020-07-31 | 中外制药株式会社 | Antibody variants and isotypes with reduced biological activity |
RU2813990C2 (en) * | 2017-11-01 | 2024-02-21 | Чугаи Сейяку Кабусики Кайся | Versions and isoforms of antibodies with reduced biological activity |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP0821695B1 (en) | Antibody purification by low-ph hydrophobic interaction chromatography | |
EP0617706B1 (en) | Multivalent antigen-binding proteins | |
US6515110B1 (en) | Multivalent antigen-binding proteins | |
CA2584211C (en) | Methods for refolding of recombinant antibodies | |
JP2002504907A (en) | Antibody preparation | |
CA2065010A1 (en) | Non-human primate cd4 polypeptides, fusions thereof, dna encoding, and uses thereof | |
WO2001007479A2 (en) | Fragments of cellular prion protein and methods useful in the diagnosis and treatment of prion diseases | |
AU766817B2 (en) | Antibody purification by low-pH hydrophobic interaction chromatography | |
US20220175918A1 (en) | Compositions and methods for modulation of antibody activity | |
EP0345811B1 (en) | Monoclonal abtibodies specific for human fibrinopeptide A | |
EP0859010A1 (en) | Anti-tpo monoclonal antibody | |
AN et al. | METHOD FOR SUPPRESSING THE IMMUNE RESPONSE | |
MXPA97005158A (en) | Monoclonal antibodies anti- |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): AL AM AT AU AZ BB BG BR BY CA CH CN CZ DE DK EE ES FI GB GE HU IS JP KE KG KP KR KZ LK LR LT LU LV MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK TJ TM TR TT UA UG UZ VN AM AZ BY KG KZ MD RU TJ TM |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): KE LS MW SD SZ UG AT BE CH DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN ML MR |
|
DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
ENP | Entry into the national phase |
Ref document number: 2214633 Country of ref document: CA Ref country code: CA Ref document number: 2214633 Kind code of ref document: A Format of ref document f/p: F |
|
WWE | Wipo information: entry into national phase |
Ref document number: 1996912575 Country of ref document: EP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 306718 Country of ref document: NZ |
|
ENP | Entry into the national phase |
Ref country code: JP Ref document number: 1996 531774 Kind code of ref document: A Format of ref document f/p: F |
|
WWP | Wipo information: published in national office |
Ref document number: 1996912575 Country of ref document: EP |
|
REG | Reference to national code |
Ref country code: DE Ref legal event code: 8642 |
|
WWG | Wipo information: grant in national office |
Ref document number: 1996912575 Country of ref document: EP |