WO2007110339A1 - Anti-igf-1r human monoclonal antibody formulation - Google Patents
Anti-igf-1r human monoclonal antibody formulation Download PDFInfo
- Publication number
- WO2007110339A1 WO2007110339A1 PCT/EP2007/052569 EP2007052569W WO2007110339A1 WO 2007110339 A1 WO2007110339 A1 WO 2007110339A1 EP 2007052569 W EP2007052569 W EP 2007052569W WO 2007110339 A1 WO2007110339 A1 WO 2007110339A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- igf
- histidine
- mlhumab
- polysorbate
- nacl
- Prior art date
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39591—Stabilisation, fragmentation
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
- C07K16/2863—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for growth factors, growth regulators
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
Definitions
- the present invention relates to an an ti- IGF- IR human monoclonal antibody formulation, a process for the preparation and uses thereof.
- the invention relates to an IGF- IR formulation comprising: - about 1 to about 150 mg/mLhuMab IGF- IR, - about 0.001 to about 1% of at least one surfactant, and about 1 to about 100 mM of a buffer, at a pH of about 5.0 to about 7.0.
- the IGF-IR (type 1 insulin-like growth factor receptor), has been implicated in promoting oncogenic transformation, growth, and survival of cancer cells. High levels of expression of IGF-IR have been reported in a broad range of human malignancies. In addition, high levels of IGF-I and IGF-II expression have been noted in tumors and associated stromal cells and may stimulate cancer cell growth in an autocrine or paracrine manner. Epidemiological studies have correlated upper quintile plasma levels of IGF-I with increased risk for prostate, colon, lung, and breast cancer. In addition to its role in proliferation of cancer cells, IGF-IR protects cells from apoptosis caused by growth factor deprivation, anchorage independence, or cytotoxic drug treatment.
- IGF-IR insulin-like growth factor I receptor
- the antibody comprised in the formulation of the invention has been first described in PCT patent application No. WO2005/005635 of which the Applicant is proprietor and the content of which, especially the claims is incorporated herein by reference.
- said antibody is binding to IGF-IR and inhibiting the binding of IGF-I and IGF-II to IGF-IR, and is characterized in that it:
- Antibodies comprised in the formulation according to the invention show benefits for patients in need of antitumor therapy and provide reduction of tumor growth and a significant prolongation of the time to progression.
- the antibodies comprised in the formulation according to the invention have new and inventive properties causing a benefit for a patient suffering from a disease associated with an IGF deregulation, especially a tumor disease.
- the antibodies comprised in the formulation of the invention are characterized by the abovementioned properties.
- the properties are therefore especially specific binding to IGF-IR, inhibiting the binding of IGF-I and IGF-II to IGF- IR at the abovementioned ratio, being of IgGl isotype, and not activating the IGF-IR signaling even in IGF-IR overexpressing cells at a 200-fold concentration of its IC 50 value.
- Antibodies having no "IGF-I mimetic activity" provide a strong advantage when used as a therapeutic agent.
- an ti- IGF- IR human monoclonal antibody or "huMAb IGF-IR” denotes an antibody as described and claimed in WO2005/005635, the content of which, especially the claims, is incorporated herein by reference.
- antibody encompasses the various forms of antibodies including but not being limited to whole antibodies, antibody fragments, human antibodies, humanized antibodies and genetically engineered antibodies as long as the characteristic properties according to the invention are retained.
- Antibody fragments comprise a portion of a full length antibody, generally at least the antigen binding portion or the variable region thereof.
- antibody fragments include diabodies, single-chain antibody molecules, immunotoxins, and multispecific antibodies formed from antibody fragments.
- antibody fragments comprise single chain polypeptides having the characteristics of a VH chain, namely being able to assemble together with a VL chain or of a VL chain binding to IGF- IR, namely being able to assemble together with a VH chain to a functional antigen binding pocket and thereby providing the property of inhibiting the binding of IGF-I and IGF-II to IGF-IR.
- Antibody fragments also comprises such fragments which per se are not able to provide effector functions (ADCC/CDC) but provide this function in a manner according to the invention after being combined with appropriate antibody constant domain (s).
- the terms “monoclonal antibody” or “monoclonal antibody composition” as used herein refer to a preparation of antibody molecules of a single amino acid composition. Accordingly, the term “human monoclonal antibody” refers to antibodies displaying a single binding specificity which have variable and constant regions derived from human germline immunoglobulin sequences. In one embodiment, the human monoclonal antibodies are produced by a hybridoma which includes a B cell obtained from a transgenic non-human animal, e.g. a transgenic mouse, having a genome comprising a human heavy chain transgene and a light human chain transgene fused to an immortalized cell.
- a transgenic non-human animal e.g. a transgenic mouse
- chimeric antibody refers to a monoclonal antibody comprising a variable region, i.e., binding region, from one source or species and at least a portion of a constant region derived from a different source or species, usually prepared by recombinant DNA techniques. Chimeric antibodies comprising a murine variable region and a human constant region are especially preferred. Such murine/human chimeric antibodies are the product of expressed immunoglobulin genes comprising DNA segments encoding murine immunoglobulin variable regions and DNA segments encoding human immunoglobulin constant regions.
- Other forms of "chimeric antibodies" encompassed by the present invention are those in which the class or subclass has been modified or changed from that of the original antibody.
- Such “chimeric” antibodies are also referred to as "class- switched antibodies.”
- Methods for producing chimeric antibodies involve conventional recombinant DNA and gene transfection techniques now well known in the art. See, e.g., Morrison, S.L., et al., Proc. Natl. Acad Sci. USA 81 (1984) 6851-6855; US Patent Nos. 5,202,238 and 5,204,244.
- humanized antibody refers to antibodies in which the framework or "complementarity determining regions” (CDR) have been modified to comprise the CDR of an immunoglobulin of different specificity as compared to that of the parent immunoglobulin.
- CDR complementarity determining regions
- a murine CDR is grafted into the framework region of a human antibody to prepare the "humanized antibody.” See, e.g., Riechmann, L, et al., Nature 332 (1988) 323-327; and Neuberger, M.S., et al., Nature 314 (1985) 268-270.
- Particularly preferred CDRs correspond to those representing sequences recognizing the antigens noted above for chimeric and bifunctional antibodies.
- human antibody is intended to include antibodies having variable and constant regions derived from human germline immunoglobulin sequences.
- the variable heavy chain is preferably derived from germline sequence DP-50 (GenBank LO6618) and the variable light chain is preferably derived from germline sequence L6 (GenBank X01668).
- the constant regions of the antibody are constant regions of human IgGl type. Such regions can be allotypic and are described by, e.g., Johnson, G., and Wu, T.T., Nucleic Acids Res. 28 (2000) 214-218 and the databases referenced therein and are useful as long as the properties of induction of ADCC and preferably CDC according to the invention are retained.
- recombinant human antibody is intended to include all human antibodies that are prepared, expressed, created or isolated by recombinant means, such as antibodies isolated from a host cell such as an SP2-0, NSO or CHO cell or from an animal (e.g. a mouse) that is transgenic for human immunoglobulin genes or antibodies expressed using a recombinant expression vector transfected into a host cell.
- recombinant human antibodies have variable and constant regions derived from human germline immunoglobulin sequences in a rearranged form.
- the recombinant human antibodies according to the invention have been subjected to in vivo somatic hypermutation.
- the amino acid sequences of the VH and VL regions of the recombinant antibodies are sequences that, while derived from and related to human germline VH and VL sequences, may not naturally exist within the human antibody germline repertoire in vivo.
- binding refers to antibody binding to IGF-IR with an affinity of about 10 "13 to 10 "8 M (K D ), preferably of about 10 "13 to 10 "9 M.
- nucleic acid molecule is intended to include DNA molecules and RNA molecules.
- a nucleic acid molecule may be single- stranded or double-stranded, but preferably is double-stranded DNA.
- the constant domains are not involved directly in binding the antibody to an antigen but are involved in the effector functions (ADCC, complement binding, and CDC).
- the constant domain of an antibody according to the invention is of the IgGl type. Human constant domains having these characteristics are described in detail by Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD. (1991), and by Br ⁇ ggemann, M., et al., J. Exp. Med. 166 (1987) 1351-1361; Love, T.W., et al., Methods Enzymol. 178 (1989) 515-527.
- hypervariable region or "antigen-binding portion of an antibody” when used herein refer to the amino acid residues of an antibody which are responsible for antigen-binding.
- the hypervariable region comprises amino acid residues from the "complementarity determining regions” or "CDRs".
- “Framework” or "FR” regions are those variable domain regions other than the hypervariable region residues as herein defined. Therefore, the light and heavy chains of an antibody comprise from N- to C- terminus the domains FRl, CDRl, FR2, CDR2, FR3, CDR3, and FR4.
- CDR3 of the heavy chain is the region which contributes most to antigen binding.
- CDR and FR regions are determined according to the standard definition of Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD. (1991)) and/or those residues from a "hypervariable loop".
- binding to IGF-IR means the binding of the antibody to IGF-IR in an in vitro assay, preferably in a binding assay in which the antibody is bound to a surface and binding of IGF-IR is measured by Surface Plasmon Resonance (SPR). Binding means a binding affinity (K D ) of 10 ⁇ 8 M or less, preferably 10 ⁇ 13 to 10 ⁇ 9 M.
- Binding to IGF-IR can be investigated by a BIAcore assay (Pharmacia Biosensor AB, Uppsala, Sweden).
- the affinity of the binding is defined by the terms ka (rate constant for the association of the antibody from the antibody/ antigen complex), kd (dissociation constant), and K D (kd/ka).
- the antibodies according to the invention show a K D of 10 ⁇ 10 M or less.
- the binding of IGF-I and IGF-II to IGF-IR is also inhibited by the antibodies according to the invention.
- the inhibition is measured as IC 50 in an assay for binding of IGF-I/IGF-II to IGF-IR on tumor cells.
- an assay for binding of IGF-I/IGF-II to IGF-IR on tumor cells.
- Such an assay is described in Example 7.
- the amount of radiolabeled IGF-I or IGF-II or IGF-IR binding fragments thereof bound to the IGF-IR provided at the surface of said tumor cells (e.g. HT29) is measured without and with increasing concentrations of the antibody.
- inhibiting the binding of IGF-I and IGF-II to IGF-IR refers to inhibiting the binding of I 125 -labeled IGF-I or IGF-II to IGF-IR presented on the surface of HT29 (ATCC HTB-38) tumor cells in an in vitro assay. Inhibiting means an IC50 value of 2 nM or lower.
- surfactant denotes a pharmaceutically acceptable surfactant.
- the amount of surfactant is described a percentage expressed in weight/volume. The most commonly used weight/volume unit is mg/mL.
- Suitable pharmaceutically acceptable surfactants comprise but are not limited to polyethylen-sorbitan-fatty acid esters, polyethylene-polypropylene glycols, polyoxyethylene-stearates and sodium dodecyl sulphates.
- Tween 20TM polyethylen-sorbitan-polyethylen(20)-sorbitan-esters
- Tween 80TM polyoxyethylen(20)sorbitanmonooleat
- buffer denotes a pharmaceutically acceptable buffer.
- Suitable pharmaceutically acceptable buffer comprise but are not limited to histidine- buffers, citrate-buffers, succinate-buffers, acetate-buffers and phosphate-buffers.
- Preferred buffers comprise L-histidine or mixtures of L-histidine with L-histidine hydrochloride with isotonicity agents and pH adjustment with an acid or a base known in the art.
- the abovementioned histidine-buffers are generally used in an amount of about ImM to about 100 mM, preferably of about 5 mM to about 50 mM and still more preferably of about 20 mM.
- the pH will be adjusted at a value comprising about 5.0 to about 7.0 and preferably about 5.5 to about 6.5 and still preferably about 6.0.
- isotonicity agents denotes pharmaceutically acceptable isotonicity agents.
- Isotonicity agents are used to provide an isotonic formulation.
- An isotonic formulation is liquid or liquid reconstituted from a solid form, e.g. a lyophilized form and denotes a solution having the same tonicity as some other solution with which it is compared, such as physiologic salt solution and the blood serum.
- Suitable isotonicity agents comprise but are not limited to sodium chloride, potassium chloride, glucose, glycerine and any component from the group of amino acids, sugars and combinations thereof.
- Isotonicity agents are generally used in a total amount of about 5 mM to about 350 mM.
- liquid as used herein in connection with the formulation according to the invention denotes a formulation which is liquid at a temperature of at least about 2 to about 8 0 C.
- lyophilized as used herein in connection with the formulation according to the invention denotes a formulation which is dried by freezing the formulation and subsequently subliming the ice from the frozen content by any freeze- drying methods known in the art, for example commercially available freeze-drying devices.
- amino acid denotes an amino acid in an amount of about 1 to about 100 mg/mL comprising but not limited to arginine, glycine, ornithine, lysine, histidine, glutamic acid, asparagic acid, isoleucine, leucine, alanine, phenylalanine, tyrosine, tryptophane, methionine, serine, proline.
- sugar as used herein denotes a pharmaceutically acceptable sugar used in an amount of about 25 mM to about 500 mM.
- Suitable sugars comprise but are not limited to trehalose, saccharose, lactose, glucose, mannose, maltose, galactose, fructose, sorbose, raffinose, glucosamine, N-Methylglucosamine (so-called "Meglumine”), galactosamine and neuraminic acid.
- stabilizer refers to pharmaceutically acceptable stabilizers, like for example but not limited to amino acids and sugars as described in the above sections as well as commercially available cyclodextrins and dextrans of any kind and molecular weight as known in the art.
- antioxidant denotes a pharmaceutically acceptable antioxidant.
- the invention relates to an IGF- IR formulation comprising:
- the formulation according to the invention preferably comprises about 0.001 to about 1% of at least one surfactant.
- the formulation according to the invention can be in a liquid form, in a lyophilized form or in a liquid form reconstituted from a lyophilized form.
- the formulation according to the invention is a lyophilized formulation.
- the lyophilized formulation according to the invention has the advantage of an improved stability with regard to the formation of particulates and aggregates of higher molecular weight that is usually difficult to be achieved with liquid formulations at the same concentration of the described an ti- IGF- IR human monoclonal antibody.
- the formulation according to the invention can be administered by intravenous (i.v.), subcutaneous (s.c.) or any other parental administration means such as those known in the pharmaceutical art.
- the formulation of the invention can further comprise one or more isotonicity agents in an amount of about 5 mM to about 350 mM.
- Suitable isotonicity agents can be selected from the group consisting of sodium chloride (NaCl), potassium chloride, sugars comprising glucose, glycerin, amino acids, and combinations thereof.
- the formulation of the invention can further comprise a sugar in an amount of about 25 mM to about 500 mM.
- Suitable sugars can be selected from the group consisting of trehalose, saccharose, lactose, glucose, mannose, maltose, galactose, fructose, sorbose, raffinose, glucosamine, N-Methylglucosamine, galactosamine, neuraminic acid and combinations thereof.
- the formulation of the invention can further comprise one or more of the following ingredients: antioxidants, ascorbic acid, Glutathion, preservatives, e.g., m- cresol, phenol, benzylalcohol, methylparaben, propylparaben, chlorbutanol, thiomersal, benzalkoniumchloride, cyclodextrine, e.g. hydroxypropyl- ⁇ -cyclodextrine, sulfobutylethyl- ⁇ -cyclodextrin, ⁇ -Cyclodextrin, polyethylenglycole, e.g.
- PEG 3000, 3350, 4000, 6000 albumine, human serum albumin (HSA), bovines serum albumin (BSA), polyhydric alcohol, glycerol, ethanol, mannitol, salts, acetate salts (e.g. sodium acetate), magnesiumchloride, calciumchloride, tromethamine, EDTA, (e.g. Na-EDTA).
- HSA human serum albumin
- BSA bovines serum albumin
- polyhydric alcohol glycerol
- ethanol ethanol
- mannitol mannitol
- salts e.g. sodium acetate
- magnesiumchloride calciumchloride
- EDTA e.g. Na-EDTA
- the formulation of the invention can further comprise one or more stabilizers as defined hereinabove and ingredients also known in the art as "lyoprotectants” such as sugars, sugar alcohols, amino acids and dextrans as known in the art.
- the formulation of the invention comprises the following formulations, either in the liquid, lyophilized or liquid reconstituted from lyophilized forms:
- the formulation according to the invention also comprises the following specific formulations:
- the formulation is in a lyophilized form and comprises after reconstitution with the appropriate amount of water for injection: - 25 mg/mLhuMab IGF-IR,
- This formulation shows a good stability upon storage for approx 6 months at 2-8 0 C and 25 0 C with high molecular weight species less than 1.5% and without the formation of visible and sub-visible particles. Shaking and multiple freezing- thawing steps were applied to the liquid formulation to simulate physical stress conditions that potentially occur during manufacturing, e.g., by pressure filtration and filling, lyophilization and finish operations. This formulation was found to be stable after one week shaking at 5 0 C and 25 0 C. Formation of visible and sub-visible particles could not be detected and no significant increase in the fraction of high molecular weight species indicating the formation of soluble aggregates was observed.
- Liquid and lyophilized drug product formulations for intravenous administration according to the invention were developed as follows: Preparation of liquid formulations
- Solutions of approx. 10 and 25 mg/mLhuMab IGF- IR in the production buffer were dialysed against large volumes of water and of the respective buffer salt systems for the final formulation (see table with the exact composition of the formulations) .
- protein concentration was increased by filtration using commercially available centrifugal filter devices) prior to dialysis and then adjusted to the desired protein concentration by dilution with dialysis buffer.
- Sugars and salt for stabilizing the protein and for tonicity adjustment were added to the dialysis buffer as required.
- Surfactant was added to the formulations after dialysis as 2 to 40-fold stock solutions.
- buffer exchange and concentration was performed using a commercially available tangential flow filtration device, e.g., AKTA CF (GE Healthcare) with a Sartorius Hydrosart membrane (30'000Da molecular weight cut-off). Ingredients such as sugars, salts or surfactants were added after the buffer exchange by using appropriate quantities of concentrated stock solutions. All formulations were sterile filtered through 0.22 ⁇ m low protein binding filters and aseptically aliquoted into sterile 6 mL glass vials closed with Teflon-coated rubber stoppers and alucrimp caps.
- AKTA CF GE Healthcare
- Sartorius Hydrosart membrane 30'000Da molecular weight cut-off
- Solutions of 25 mg/mL huMab IGF- IR were prepared as described above for liquid formulations. All formulations were sterile filtered through 0.22 ⁇ m low protein binding filters and aseptically aliquoted into sterile glass vials. The vials were partly closed with Teflon-coated rubber stoppers suitable for the use in lyphilization processes and transferred to the drying chamber of the lyophilizer. Any lyophilization method known in the art is intended to be within the scope of the invention.
- the lyophilization process used for this study included the cooling of the formulation from room temperature to approx 5 0 C (pre-cooling) followed by a freezing at -4O 0 C (Freeze I) at a ramping rate of about l°C/min to 5°C/min.
- the first drying step can be applied at a ramping rate of 0.3 to 0.5 0 C / min from -4O 0 C to -3O 0 C and then hold at -3O 0 C for at least 50 hours at a chamber pressure of approx. 75 to 80 mTorr.
- a second drying step can take place at a ramping rate of 0.1 to 0.3 0 C / min from -3O 0 C to 25 0 C and hold at 25 0 C for at least 5 hours at a chamber pressure of about 50 to 80 mTorr.
- huMab IGF- IR formulations which were dried using the described lyophilization processes were found to have conveniently quick reconstitution times of about ⁇ 5 min. Lyophilization was carried out in a LyoStar II Freeze-dryer (FTS Systems, Stone Ridge, NY, USA and Usifroid Orion, Maurepas, France). All lyophilized cakes in this study had a residual water content of approximately 0.1 to 5.0% as determined by Karl- Fischer method.
- the lyophilized vials were stored at different temperatures for different intervals of time.
- the lyophilized formulations were reconstituted with the respective volume of water for injection (WFI) prior to analysis by 1) UV sprectrophotometry, 2) determination of the reconstitution time, 3) Size Exclusion Chromatography (SEC) and 4) light obscuration to determine the turbidity of the solution.
- WFI water for injection
- SEC Size Exclusion Chromatography
- analysis for visible particles was performed for each sample using a Seidenader V90-T instrument (Seidenader, Tschwaben, Germany). Occurrence of subvisible particles was assessed by a HIAC Royco device.
- SEC Size Exclusion Chromatography
- Formulation A is a liquid formulation with the composition 25 mg/mL huMab IGF- IR, 20 mM L-histidine, 140 mM NaCl, 0.01% polysorbate 20, at pH 6.0.
- Formulation B is a liquid formulation with the composition 25 mg/mL huMab IGF-IR, 20 mM L-histidine, 140 mM NaCl, 0.03% polysorbate 20, at pH 6.0.
- Formulation C is a liquid formulation with the composition 25 mg/mL huMab IGF-IR, 20 mM L-histidine, 140 mM NaCl, 0.05% polysorbate 20, at pH 6.0.
- Formulation D is a liquid formulation with the composition 10 mg/mL huMab IGF-IR, 20 mM L-histidine, 140 mM NaCl, 0.01% polysorbate 20, at pH 6.0
- Formulation E is a liquid formulation with the composition 10 mg/mL huMab IGF- IR, 20 mM L-histidine, 140 mM NaCl, 0.03% polysorbate 20, at pH 6.0.
- Formulation F is a liquid formulation with the composition 10 mg/mL huMab IGF- IR, 20 mM L-histidine, 140 mM NaCl, 0.05% polysorbate 20, at pH 6.0
- Formulation G is a liquid formulation with the composition 10 mg/mL huMab IGF-IR, 20 mM L-histidine, 140 mM NaCl, at pH 5.5.
- Formulation H is a liquid formulation with the composition 25 mg/mL huMab IGF-IR, 20 mM L-histidine, 250 mM trehalose dihydrate, 0.01% polysorbate 20, at pH 5.5
- Formulation I is a liquid formulation with the composition 25 mg/mLhuMab IGF-IR, 20 mM L-histidine, 250 mM trehalose dihydrate, at pH 6.0
- Formulation J is a liquid formulation with the composition 25 mg/mL huMab IGF- IR, 20 mM L-histidine, 250 mM trehalose dihydrate, 0.01% polysorbate 20, at pH 6.0
- Formulation K is a liquid formulation with the composition 25 mg/mL huMab IGF- IR, 20 mM L-histidine, 250 mM trehalose dihydrate, 0.05% polysorbate 20, at pH 6.0
- Formulation L is a liquid formulation with the composition 25 mg/mL huMab IGF-IR, 20 mM L-histidine, 60 mM trehalose dihydrate, 0.01% polysorbate 20, at pH 6.0
- Formulation M is a liquid formulation with the composition 25 mg/mL huMab IGF-IR, 20 mM succinate, 250 mM trehalose dihydrate, 0.01% polysorbate 20, at pH 5.5
- Formulation N is a lyophilized formulation with the composition of the reconstituted solution of 25 mg/mLhuMab IGF-IR, 20 mM L-histidine, 60 mM trehalose dihydrate, 0.01% polysorbate 20, at pH 6.0
- Formulation O is a lyophilized formulation with the composition of the reconstituted solution of 25 mg/mLhuMab IGF-IR, 20 mM L-histidine, 60 mM sucrose, 0.01% polysorbate 20, at pH 6.0
- Formulation P is a lyophilized formulation with the composition of the reconstituted solution of 25 mg/mLhuMab IGF-IR, 20 mM succinate, 250 mM trehalose dihydrate, 0.01% polysorbate 20, at pH 5.5
- Formulation Q is a lyophilized formulation with the composition of the reconstituted solution of 25 mg/mLhuMab IGF-IR, 20 mM L-histidine, 250 mM trehalose dihydrate, 0.01% polysorbate 20, at pH 5.5
Abstract
Description
Claims
Priority Applications (8)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2009502016A JP2009531371A (en) | 2006-03-28 | 2007-03-19 | Anti-IGF-1R human monoclonal antibody preparation |
CA002647111A CA2647111A1 (en) | 2006-03-28 | 2007-03-19 | Anti-igf-1r human monoclonal antibody formulation |
AU2007229554A AU2007229554A1 (en) | 2006-03-28 | 2007-03-19 | Anti-IGF-1R human monoclonal antibody formulation |
MX2008012295A MX2008012295A (en) | 2006-03-28 | 2007-03-19 | Anti-igf-1r human monoclonal antibody formulation. |
EP07727047A EP1998806A1 (en) | 2006-03-28 | 2007-03-19 | Anti-igf-1r human monoclonal antibody formulation |
BRPI0709229-6A BRPI0709229A2 (en) | 2006-03-28 | 2007-03-19 | anti-igf-ir human monoclonal antibody formulation |
IL193904A IL193904A0 (en) | 2006-03-28 | 2008-09-04 | Anti-igf-1r human monoclonal antibody formulation |
NO20083895A NO20083895L (en) | 2006-03-28 | 2008-09-11 | Anti-IGF-1R human monoclonal antibody formulation |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP06111848 | 2006-03-28 | ||
EP06111848.5 | 2006-03-28 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2007110339A1 true WO2007110339A1 (en) | 2007-10-04 |
Family
ID=37025222
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP2007/052569 WO2007110339A1 (en) | 2006-03-28 | 2007-03-19 | Anti-igf-1r human monoclonal antibody formulation |
Country Status (18)
Country | Link |
---|---|
EP (1) | EP1998806A1 (en) |
JP (1) | JP2009531371A (en) |
KR (1) | KR20080104160A (en) |
CN (1) | CN101410137A (en) |
AR (1) | AR060130A1 (en) |
AU (1) | AU2007229554A1 (en) |
BR (1) | BRPI0709229A2 (en) |
CA (1) | CA2647111A1 (en) |
CL (1) | CL2007000797A1 (en) |
CR (1) | CR10295A (en) |
EC (1) | ECSP088778A (en) |
IL (1) | IL193904A0 (en) |
MA (1) | MA30345B1 (en) |
MX (1) | MX2008012295A (en) |
NO (1) | NO20083895L (en) |
RU (1) | RU2008142359A (en) |
TW (1) | TW200815029A (en) |
WO (1) | WO2007110339A1 (en) |
Cited By (24)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2008071394A1 (en) * | 2006-12-11 | 2008-06-19 | F. Hoffmann-La Roche Ag | Abeta antibody parenteral formulation |
WO2008098917A2 (en) * | 2007-02-14 | 2008-08-21 | Glaxo Group Limited | Novel antibodies against igf-ir |
WO2009007272A1 (en) * | 2007-07-10 | 2009-01-15 | F. Hoffmann-La Roche Ag | Novel formulation |
WO2009068282A1 (en) * | 2007-11-29 | 2009-06-04 | F. Hoffmann-La Roche Ag | Immunoglobulin aggregates |
US20090162352A1 (en) * | 2007-12-21 | 2009-06-25 | Michael Adler | Antibody formulation |
EP2136839A2 (en) * | 2007-03-22 | 2009-12-30 | Imclone LLC | Stable antibody formulations |
WO2010069858A1 (en) * | 2008-12-19 | 2010-06-24 | F. Hoffmann-La Roche Ag | Pharmaceutical composition |
WO2010146059A2 (en) | 2009-06-16 | 2010-12-23 | F. Hoffmann-La Roche Ag | Biomarkers for igf-1r inhibitor therapy |
WO2016057739A1 (en) * | 2014-10-09 | 2016-04-14 | Regeneron Pharmaceuticals, Inc. | Process for reducing subvisible particles in a pharmaceutical formulation |
US9345661B2 (en) | 2009-07-31 | 2016-05-24 | Genentech, Inc. | Subcutaneous anti-HER2 antibody formulations and uses thereof |
CN106999591A (en) * | 2015-09-28 | 2017-08-01 | 江苏恒瑞医药股份有限公司 | A kind of antibody preparations of anti-PD 1 and its in application pharmaceutically |
EP2691112B1 (en) | 2011-03-31 | 2018-05-23 | Merck Sharp & Dohme Corp. | Stable formulations of antibodies to human programmed death receptor pd-1 and related treatments |
US10280227B2 (en) | 2009-09-11 | 2019-05-07 | Genentech, Inc. | Highly concentrated pharmaceutical formulations |
US10941205B2 (en) | 2015-10-02 | 2021-03-09 | Hoffmann-La Roche Inc. | Bispecific anti-human A-beta/human transferrin receptor antibodies and methods of use |
US11091541B2 (en) | 2013-04-29 | 2021-08-17 | Hoffmann-La Roche Inc. | Human FcRn-binding modified antibodies and methods of use |
CN114324882A (en) * | 2020-10-12 | 2022-04-12 | 广东菲鹏生物有限公司 | Protein stabilizer and application thereof |
US11333642B2 (en) | 2016-10-25 | 2022-05-17 | Regeneran Pharmaceuticals, Inc. | Methods and systems for chromatography data analysis |
US11369896B2 (en) | 2016-08-16 | 2022-06-28 | Regeneron Pharmaceuticals, Inc. | Methods for quantitating individual antibodies from a mixture |
US11555067B2 (en) | 2014-01-15 | 2023-01-17 | Hoffmann-La Roche Inc. | Fc-region variants with improved protein A-binding |
US11584793B2 (en) | 2015-06-24 | 2023-02-21 | Hoffmann-La Roche Inc. | Anti-transferrin receptor antibodies with tailored affinity |
US11603411B2 (en) | 2015-10-02 | 2023-03-14 | Hoffmann-La Roche Inc. | Bispecific anti-human CD20/human transferrin receptor antibodies and methods of use |
US11633476B2 (en) | 2017-05-02 | 2023-04-25 | Merck Sharp & Dohme Llc | Stable formulations of programmed death receptor 1 (PD-1) antibodies and methods of use thereof |
US11845798B2 (en) | 2017-05-02 | 2023-12-19 | Merck Sharp & Dohme Llc | Formulations of anti-LAG3 antibodies and co-formulations of anti-LAG3 antibodies and anti-PD-1 antibodies |
US11884698B2 (en) | 2018-07-02 | 2024-01-30 | Regeneron Pharmaceuticals, Inc. | Systems and methods for preparing a polypeptide from a mixture |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102686241A (en) * | 2009-12-29 | 2012-09-19 | 霍夫曼-拉罗奇有限公司 | Antibody formulation |
US20130136733A1 (en) * | 2010-05-28 | 2013-05-30 | Novo Nordisk A/S | Stable Multi-Dose Compositions Comprising an Antibody and a Preservative |
CN102363040B (en) * | 2011-10-21 | 2013-05-01 | 北京锐瑟科技有限公司 | Antimicrobial peptide preparation for mucosal tissues |
CN103505729B (en) * | 2013-05-24 | 2015-10-28 | 华北制药集团新药研究开发有限责任公司 | A kind of stable rabies virus human antibody combination preparation |
CN104707146B (en) * | 2013-12-16 | 2019-04-16 | 浙江海正药业股份有限公司 | A kind of pharmaceutical composition containing adalimumab |
JP6707469B2 (en) * | 2014-05-28 | 2020-06-10 | ノノ インコーポレイテッド | Lyophilized formulation of Tat-NR2B9c containing acetylated scavenger |
CN106199007B (en) * | 2016-08-03 | 2017-04-05 | 烟台普罗吉生物科技发展有限公司 | Protein protective agent |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1998056418A1 (en) * | 1997-06-13 | 1998-12-17 | Genentech, Inc. | Stabilized antibody formulation |
US20030113316A1 (en) * | 2001-07-25 | 2003-06-19 | Kaisheva Elizabet A. | Stable lyophilized pharmaceutical formulation of IgG antibodies |
WO2004087756A2 (en) * | 2003-04-02 | 2004-10-14 | F. Hoffmann-La Roche Ag | Antibodies against insulin-like growth factor i receptor and uses thereof |
WO2004091658A1 (en) * | 2003-04-04 | 2004-10-28 | Genentech, Inc. | High concentration antibody and protein formulations |
WO2005005635A2 (en) * | 2003-07-10 | 2005-01-20 | F. Hoffmann-La Roche Ag | Antibodies against insulin-like growth factor i receptor and uses thereof |
US20050069539A1 (en) * | 2003-08-13 | 2005-03-31 | Pfizer Inc | Modified human IGF-IR antibodies |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AR032028A1 (en) * | 2001-01-05 | 2003-10-22 | Pfizer | ANTIBODIES AGAINST THE RECEIVER OF THE SIMILAR TO INSULIN GROWTH FACTOR |
-
2007
- 2007-03-19 AU AU2007229554A patent/AU2007229554A1/en not_active Abandoned
- 2007-03-19 KR KR1020087023673A patent/KR20080104160A/en not_active Application Discontinuation
- 2007-03-19 MX MX2008012295A patent/MX2008012295A/en active IP Right Grant
- 2007-03-19 BR BRPI0709229-6A patent/BRPI0709229A2/en not_active IP Right Cessation
- 2007-03-19 CN CNA2007800114320A patent/CN101410137A/en active Pending
- 2007-03-19 EP EP07727047A patent/EP1998806A1/en not_active Withdrawn
- 2007-03-19 JP JP2009502016A patent/JP2009531371A/en active Pending
- 2007-03-19 WO PCT/EP2007/052569 patent/WO2007110339A1/en active Application Filing
- 2007-03-19 RU RU2008142359/15A patent/RU2008142359A/en not_active Application Discontinuation
- 2007-03-19 CA CA002647111A patent/CA2647111A1/en not_active Abandoned
- 2007-03-26 AR ARP070101241A patent/AR060130A1/en not_active Application Discontinuation
- 2007-03-26 TW TW096110388A patent/TW200815029A/en unknown
- 2007-03-26 CL CL2007000797A patent/CL2007000797A1/en unknown
-
2008
- 2008-09-04 IL IL193904A patent/IL193904A0/en unknown
- 2008-09-11 NO NO20083895A patent/NO20083895L/en not_active Application Discontinuation
- 2008-09-17 CR CR10295A patent/CR10295A/en not_active Application Discontinuation
- 2008-09-26 EC EC2008008778A patent/ECSP088778A/en unknown
- 2008-10-20 MA MA31308A patent/MA30345B1/en unknown
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1998056418A1 (en) * | 1997-06-13 | 1998-12-17 | Genentech, Inc. | Stabilized antibody formulation |
US20030113316A1 (en) * | 2001-07-25 | 2003-06-19 | Kaisheva Elizabet A. | Stable lyophilized pharmaceutical formulation of IgG antibodies |
WO2004087756A2 (en) * | 2003-04-02 | 2004-10-14 | F. Hoffmann-La Roche Ag | Antibodies against insulin-like growth factor i receptor and uses thereof |
WO2004091658A1 (en) * | 2003-04-04 | 2004-10-28 | Genentech, Inc. | High concentration antibody and protein formulations |
WO2005005635A2 (en) * | 2003-07-10 | 2005-01-20 | F. Hoffmann-La Roche Ag | Antibodies against insulin-like growth factor i receptor and uses thereof |
US20050069539A1 (en) * | 2003-08-13 | 2005-03-31 | Pfizer Inc | Modified human IGF-IR antibodies |
Non-Patent Citations (2)
Title |
---|
B. COHEN ET AL.: "Combination therapy enhances the inhibition of tumor growth with the fully human anti-type 1 insulin-like growth factor receptor monoclonal antibody CP-751,871.", CLINICAL CANCER RESEARCH, vol. 11, no. 5, 1 March 2005 (2005-03-01), U.S.A., pages 2063 - 2073, XP002433667 * |
D. BURTRUM ET AL.: "A fully human monoclonal antibody to the insulin-like growth factor I receptor blocks ligand-dependent signaling and inhibits human tumor growth in vivo.", CANCER RESEARCH, vol. 63, no. 24, 15 December 2003 (2003-12-15), U.S.A., pages 8912 - 8921, XP002316542 * |
Cited By (36)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2008071394A1 (en) * | 2006-12-11 | 2008-06-19 | F. Hoffmann-La Roche Ag | Abeta antibody parenteral formulation |
WO2008098917A2 (en) * | 2007-02-14 | 2008-08-21 | Glaxo Group Limited | Novel antibodies against igf-ir |
WO2008098917A3 (en) * | 2007-02-14 | 2008-10-09 | Glaxo Group Ltd | Novel antibodies against igf-ir |
EP2136839A2 (en) * | 2007-03-22 | 2009-12-30 | Imclone LLC | Stable antibody formulations |
EP2136839A4 (en) * | 2007-03-22 | 2010-04-07 | Imclone Llc | Stable antibody formulations |
WO2009007272A1 (en) * | 2007-07-10 | 2009-01-15 | F. Hoffmann-La Roche Ag | Novel formulation |
WO2009068282A1 (en) * | 2007-11-29 | 2009-06-04 | F. Hoffmann-La Roche Ag | Immunoglobulin aggregates |
US20090162352A1 (en) * | 2007-12-21 | 2009-06-25 | Michael Adler | Antibody formulation |
JP2011506538A (en) * | 2007-12-21 | 2011-03-03 | エフ.ホフマン−ラ ロシュ アーゲー | Antibody formulation |
KR101247418B1 (en) * | 2007-12-21 | 2013-03-25 | 에프. 호프만-라 로슈 아게 | Antibody formulation |
WO2010069858A1 (en) * | 2008-12-19 | 2010-06-24 | F. Hoffmann-La Roche Ag | Pharmaceutical composition |
WO2010146059A2 (en) | 2009-06-16 | 2010-12-23 | F. Hoffmann-La Roche Ag | Biomarkers for igf-1r inhibitor therapy |
US9345661B2 (en) | 2009-07-31 | 2016-05-24 | Genentech, Inc. | Subcutaneous anti-HER2 antibody formulations and uses thereof |
US10377831B2 (en) | 2009-09-11 | 2019-08-13 | Genentech, Inc. | Highly concentrated pharmaceutical formulations |
US10752696B2 (en) | 2009-09-11 | 2020-08-25 | Genentech, Inc. | Highly concentrated pharmaceutical formulations |
US10280227B2 (en) | 2009-09-11 | 2019-05-07 | Genentech, Inc. | Highly concentrated pharmaceutical formulations |
EP2691112B1 (en) | 2011-03-31 | 2018-05-23 | Merck Sharp & Dohme Corp. | Stable formulations of antibodies to human programmed death receptor pd-1 and related treatments |
US11091541B2 (en) | 2013-04-29 | 2021-08-17 | Hoffmann-La Roche Inc. | Human FcRn-binding modified antibodies and methods of use |
US11555067B2 (en) | 2014-01-15 | 2023-01-17 | Hoffmann-La Roche Inc. | Fc-region variants with improved protein A-binding |
US10342876B2 (en) | 2014-10-09 | 2019-07-09 | Regeneron Pharmaceuticals, Inc. | Process for reducing subvisible particles in a pharmaceutical formulation |
WO2016057739A1 (en) * | 2014-10-09 | 2016-04-14 | Regeneron Pharmaceuticals, Inc. | Process for reducing subvisible particles in a pharmaceutical formulation |
US11584793B2 (en) | 2015-06-24 | 2023-02-21 | Hoffmann-La Roche Inc. | Anti-transferrin receptor antibodies with tailored affinity |
CN106999591A (en) * | 2015-09-28 | 2017-08-01 | 江苏恒瑞医药股份有限公司 | A kind of antibody preparations of anti-PD 1 and its in application pharmaceutically |
RU2731418C2 (en) * | 2015-09-28 | 2020-09-02 | Сучжоу Санкадия Биофармасьютикалз Ко., Лтд. | Stable pharmaceutical preparation based on the pd-1 antibody and its use in medicine |
EP3357508A4 (en) * | 2015-09-28 | 2019-04-24 | Suzhou Suncadia Biopharmaceuticals Co., Ltd. | Stable anti-pd-1 antibody pharmaceutical preparation and application thereof in medicine |
US11603411B2 (en) | 2015-10-02 | 2023-03-14 | Hoffmann-La Roche Inc. | Bispecific anti-human CD20/human transferrin receptor antibodies and methods of use |
US10941205B2 (en) | 2015-10-02 | 2021-03-09 | Hoffmann-La Roche Inc. | Bispecific anti-human A-beta/human transferrin receptor antibodies and methods of use |
US11369896B2 (en) | 2016-08-16 | 2022-06-28 | Regeneron Pharmaceuticals, Inc. | Methods for quantitating individual antibodies from a mixture |
US11571636B2 (en) | 2016-08-16 | 2023-02-07 | Regeneron Pharmaceuticals, Inc. | Methods for quantitating individual antibodies from a mixture |
US11850535B2 (en) | 2016-08-16 | 2023-12-26 | Regeneron Pharmaceuticals, Inc. | Methods for quantitating individual antibodies from a mixture |
US11333642B2 (en) | 2016-10-25 | 2022-05-17 | Regeneran Pharmaceuticals, Inc. | Methods and systems for chromatography data analysis |
US11680930B2 (en) | 2016-10-25 | 2023-06-20 | Regeneron Pharmaceuticals, Inc. | Methods and systems for chromatography data analysis |
US11633476B2 (en) | 2017-05-02 | 2023-04-25 | Merck Sharp & Dohme Llc | Stable formulations of programmed death receptor 1 (PD-1) antibodies and methods of use thereof |
US11845798B2 (en) | 2017-05-02 | 2023-12-19 | Merck Sharp & Dohme Llc | Formulations of anti-LAG3 antibodies and co-formulations of anti-LAG3 antibodies and anti-PD-1 antibodies |
US11884698B2 (en) | 2018-07-02 | 2024-01-30 | Regeneron Pharmaceuticals, Inc. | Systems and methods for preparing a polypeptide from a mixture |
CN114324882A (en) * | 2020-10-12 | 2022-04-12 | 广东菲鹏生物有限公司 | Protein stabilizer and application thereof |
Also Published As
Publication number | Publication date |
---|---|
AU2007229554A1 (en) | 2007-10-04 |
MA30345B1 (en) | 2009-04-01 |
CL2007000797A1 (en) | 2008-01-25 |
CN101410137A (en) | 2009-04-15 |
BRPI0709229A2 (en) | 2011-06-28 |
TW200815029A (en) | 2008-04-01 |
CR10295A (en) | 2008-10-06 |
JP2009531371A (en) | 2009-09-03 |
NO20083895L (en) | 2008-10-24 |
ECSP088778A (en) | 2008-10-31 |
AR060130A1 (en) | 2008-05-28 |
MX2008012295A (en) | 2008-10-09 |
CA2647111A1 (en) | 2007-10-04 |
IL193904A0 (en) | 2011-08-01 |
KR20080104160A (en) | 2008-12-01 |
RU2008142359A (en) | 2010-05-10 |
EP1998806A1 (en) | 2008-12-10 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
WO2007110339A1 (en) | Anti-igf-1r human monoclonal antibody formulation | |
US20100158919A1 (en) | Pharmaceutical Composition | |
KR102614259B1 (en) | Stable formulations of antibodies to human programmed death receptor pd-1 and related treatments | |
JP2020518599A (en) | Stable preparation of programmed death receptor 1 (PD-1) antibody and method of using the same | |
US20100158925A1 (en) | Lyophilized formulations of anti-egfr antibodies | |
US20100260766A1 (en) | Stable antibody formulations | |
KR20180100439A (en) | A pharmaceutical composition comprising a bispecific antibody construct | |
TW201420601A (en) | Stable formulations of antibodies to TSLP | |
WO2007095337A2 (en) | Antibody formulation | |
TWI761869B (en) | Formulation containing anti-cd47 / pd-l1 bispecific antibody and preparation and use thereof | |
CN112822999A (en) | CSF-1R antibody formulations | |
JP2023538669A (en) | Pharmaceutical formulations containing BITE, bispecific antibodies, and methionine | |
JP7475335B2 (en) | CSF-1R antibody preparation | |
KR20220044286A (en) | Formulations comprising anti-PD-1/HER2 bispecific antibodies, methods for their preparation and uses | |
CN114832102A (en) | Stable anti-EGFR antibody composition |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
DPE2 | Request for preliminary examination filed before expiration of 19th month from priority date (pct application filed from 20040101) | ||
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 07727047 Country of ref document: EP Kind code of ref document: A1 |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2007727047 Country of ref document: EP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 570970 Country of ref document: NZ |
|
WWE | Wipo information: entry into national phase |
Ref document number: 193904 Country of ref document: IL |
|
WWE | Wipo information: entry into national phase |
Ref document number: 12008502001 Country of ref document: PH |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2007229554 Country of ref document: AU |
|
WWE | Wipo information: entry into national phase |
Ref document number: CR2008-010295 Country of ref document: CR |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2647111 Country of ref document: CA Ref document number: 08100204 Country of ref document: CO |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2008091593 Country of ref document: EG |
|
WWE | Wipo information: entry into national phase |
Ref document number: MX/a/2008/012295 Country of ref document: MX Ref document number: 2009502016 Country of ref document: JP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 5187/CHENP/2008 Country of ref document: IN Ref document number: 1020087023673 Country of ref document: KR |
|
WWE | Wipo information: entry into national phase |
Ref document number: 200780011432.0 Country of ref document: CN |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
ENP | Entry into the national phase |
Ref document number: 2007229554 Country of ref document: AU Date of ref document: 20070319 Kind code of ref document: A |
|
ENP | Entry into the national phase |
Ref document number: 2008142359 Country of ref document: RU Kind code of ref document: A |
|
ENP | Entry into the national phase |
Ref document number: PI0709229 Country of ref document: BR Kind code of ref document: A2 Effective date: 20080926 |