WO1998023289A1 - MODULATION OF IgG BINDING TO FcRn - Google Patents

MODULATION OF IgG BINDING TO FcRn Download PDF

Info

Publication number
WO1998023289A1
WO1998023289A1 PCT/US1997/021437 US9721437W WO9823289A1 WO 1998023289 A1 WO1998023289 A1 WO 1998023289A1 US 9721437 W US9721437 W US 9721437W WO 9823289 A1 WO9823289 A1 WO 9823289A1
Authority
WO
WIPO (PCT)
Prior art keywords
igg
fcrn
molecule
native
animal
Prior art date
Application number
PCT/US1997/021437
Other languages
French (fr)
Inventor
Esther Jacobowitz Israel
Neil E. Simister
Original Assignee
The General Hospital Corporation
Brandeis University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by The General Hospital Corporation, Brandeis University filed Critical The General Hospital Corporation
Publication of WO1998023289A1 publication Critical patent/WO1998023289A1/en

Links

Classifications

    • BPERFORMING OPERATIONS; TRANSPORTING
    • B82NANOTECHNOLOGY
    • B82YSPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y5/00Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6801Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
    • A61K47/6803Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6891Pre-targeting systems involving an antibody for targeting specific cells
    • A61K47/6893Pre-targeting systems involving an antibody for targeting specific cells clearing therapy or enhanced clearance, i.e. using an antibody clearing agents in addition to T-A and D-M
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides

Definitions

  • Immunoglobulin G is used intravenously to treat a number of diseases that involve immune deficiencies, including acquired immune deficiency syndrome (AIDS) , idiopathic thrombocytopenic purpura (ITP) , Kawasaki disease, Guillaine-Barre Syndrome, and dermatomyositis. Recently, there has also been increasing use in immunosuppression in transplanted patients, and in specifically directed antibody therapy, such as monoclonal antibodies used as a form of cancer chemotherapy.
  • AIDS acquired immune deficiency syndrome
  • ITP idiopathic thrombocytopenic purpura
  • FcRn in binding to IgG, sequesters it and protects it from degradation.
  • FcRn is a receptor found on the intestinal surface of the neonate, and is responsible for the shuttling of maternal milk IgG from the intestinal lumen through the intestinal epithelial cell into the systemic circulation. It is now known also to be responsible for preventing IgG from being cleared from the animal's circulation.
  • an IgG molecule that has one or more amino acid additions, deletions, or substitutions (conservative or nonconservative) in the region that binds to FcRn, thereby either increasing or decreasing the molecule's affinity for FcRn.
  • An increase in affinity would translate into the altered IgG's having a longer half-life in vivo than native IgG, while a decrease in affinity for FcRn would have the opposite effect.
  • IgG with an increased half-life in vivo would be useful in treating conditions such as acquired immune deficiency syndrome (AIDS) or idiopathic thrombocytopenic purpura (ITP) , where maintaining a higher-than-normal concentration of circulating IgG is desirable.
  • AIDS acquired immune deficiency syndrome
  • ITPP idiopathic thrombocytopenic purpura
  • a mutant IgG molecule that binds less strongly to FcRn and is therefore cleared more rapidly would be of benefit where the IgG is being used for chemotherapy or as a tumor imaging agent.
  • the mutated IgG of the invention would have amino acid substitutions in the FcRn-binding region only, resulting in altered half-life only, with no substantial change in overall immune function.
  • Also claimed is a method of removing IgG from the blood of an animal by administration of soluble FcRn, which would complex with the circulating antibody and prevent it from being sequestered by cellular FcRn. This method would be especially useful in chemotherapies, to control the ratios of tumor-bound to circulating antibodies.
  • Figure 2 is a diagram illustrating partial amino acid sequences of IgG molecules used in this study (EU numbering) . Alternative amino acid residues within an isotype are shown below the most common sequence. Sequences are from Kabat et al., 1991, Sequences of proteins of immunological interest, 5th edn. , pg. 683, NIH, Bethesda, MD. Predicted contacts with FcRn (from Burmeister et al., 1994, Nature 372:379) are underlined. Residues for binding to FcRn (Kim et al., 1994, Eur. J. Immunol. 24:2429; Raghavan et al., 1995, Biochemistry 34:14649) are marked with an asterisk.
  • FIG. 3 is an illustration depicting the proposed role for FcRn in protecting IgG from degradation.
  • IgG taken up in the fluid phase binds FcRn at acidic pH in early endosomes.
  • IgG bound to FcRn is recycled to the plasma membrane and released, whereas unbound proteins are sorted to lysosomes and degraded.
  • the altered IgG's of the invention are most readily prepared by standard reco binant DNA methods, e.g. site-directed mutagenesis or PCR.
  • the regions of IgG to be mutated corresponds to amino acids 248 through 257, 308 through 314, and 429 through 436 of IgG. Within these regions, five particular amino acid residues have been identified as being important in FcRn binding, but others can be explored as well by using DNA primer-based site-directed mutagenesis, available commercially as a kit (Amersham, Arlington Heights, Illinois) , and well known in the art.
  • the Amersham kit can be used according to the manufacturer's instructions in order to mutate specific residues within the FcRn-binding region.
  • Preliminary in vitro comparison of the binding of non-native IgG molecules relative to native IgG is done by radiolabelling the IgG molecules, incubating them with cells which express FcRn, washing the cells, and then measuring the amount of radioactivity that remains in association with the cells.
  • Suitable cells include endothelial cells, cells (such as human embryonic kidney cell line 293) transfected with a vector encoding FcRn, or intestinal epithelial cells from suckling rats or mice.
  • a brush border fraction derived from such intestinal epithelial cells prepared in accordance with standard methods (e.g., Wallace and Rees, 1980, Biochem. J. 188:9).
  • the mutant IgG antibodies can be tested for in vivo half life by radiolabelling with Na 125 I (DuPont, Wilmington, DE) using the IodogenTM method (Pierce Biochemical, Rockford, IL) . Free iodine is removed by gel filtration on Sephadex G-25 and aggregated immunoglobulins are removed by gel filtration on Sephadex G-200. The 125 I-immunoglobulin can then be diluted in 10% normal mouse serum to an injection concentration of 1 x 10 7 cpm / 150 ⁇ l.
  • mice can be injected in the jugular vein with 150 ⁇ l of the radiolabelled immunoglobulin, and subsequently bled with capillary tubes from the retro-orbital sinus at serial time points following injection.
  • Plasma would be collected by centrifugation and total radioactivity measured in a gamma counter and expressed as cpm/mg blood. The percentage radioactivity remaining in the blood after the last bleed would be calculated relative to the value 1 minute after injection. Protein-bound radioactivity would be measured by precipitation of the plasma in 10% TCA.
  • the clearance curves for the various radiolabelled antibodies can then be plotted, revealing which produce antibodies with the desired characteristics.
  • immunoprecipitation or ELISA assays can be used to ensure that the antibody does in fact complex with the antigen of interest.
  • the mutated immunoglobulins of the invention can be humanized by methods known in the art, e.g. , monoclonal antibodies can be commercially humanized (Scotgen, Scotland; Oxford Molecular, Palo Alto, CA) .
  • the antibodies can then be purified using known methods, such as absorption onto immobilized Protein A or immunoaffinity chromatography.
  • the antibodies of the invention can be administered to patients in a pharmaceutically acceptable excipient such as physiological saline.
  • the antibodies of the present invention can be administered by any standard route including intravenously, intraperitoneally, intramuscularly, or subcutaneously. It is expected that the preferred route of administration will be intravenous.
  • dosages for any one patient depends on many factors, including the patients general health, sex, size, body surface area, age, as well as the particular compound to be administered, time and route of administration, and other drugs being administered concurrently. Determination of correct dosage for a given application is well within the abilities of one of ordinary skill in the art of pharmacology.
  • the invention also includes screening methods for identifying IgG molecules with altered circulating half- lives and binding affinities relative to native IgG.
  • Example 1 Increased clearing in mice that lack 02- microglobulin.
  • the clearance experiments were done at 8 weeks of age. The mice were given 0.01% Nal in their drinking water one day prior to injection and throughout the period of monitoring clearance of the 125 I-immunoglobulins.
  • Precipitation in 10% trichloroacetic acid (TCA) showed that at least 90% of the 125 I in preparations of IgGl, IgG3, and IgY was bound to protein, and at least 80% of the radiolabel in IgG2a and IgG2b was bound to protein.
  • the 125 I-immunoglobulin was diluted in 10% normal mouse serum to achieve approximately 1 x 10 7 cpm/150 ⁇ l for injection. Clearance experiments: Under pentobarbitol anesthesia
  • mice (65 ⁇ g/g body weight) , the external jugular veins of 32m- /-, 32m+/ ⁇ f and 32m+/+ mice were exposed and injected with approximately 150 ⁇ l of the 125 I-immunoglobulin diluted in 10% normal mouse serum.
  • the mice were bled with capillary tubes from the retro-orbital sinus at serial time points following injection, under light isotharine anesthesia. Plasma was collected by centrifugation and total radioactivity was measured in a gamma counter and expressed as cpm/mg blood. After the last bleed, the animals were killed with C0 2 . The percentage radioactivity remaining in blood was calculated relative to the value 1 min. after injection. Protein-bound radioactivity was measured by precipitation of the plasma in 10% TCA. This protocol has been approved by the Institutional Animal Care and Use
  • Pharmacokinetic data analysis The data from each animal were fitted to a double exponential model, c _ e b- 2t + e a-(kl+k2)t by a non-linear least squares method with a multiplicative error structure.
  • the parameters kl and k2 were constrained to be positive.
  • the area under the curve at infinity (AUC ⁇ ) , mean residence time (MRT) , terminal elimination half life (t 1 / 2 ) , and the phase I half life were then calculated from a, b, kl, and k2.
  • Means and s.e. .s for these parameters were calculated for each genotype group. Differences between the groups were tested with an analysis of variance using Gabriel's procedure to make pairwise comparisons (Gabriel, 1978, J. Amer. Statistical Assoc. 73:724).
  • FIG. 1 is a graph showing the clearance of intravenously injected 125 I-labelled immunoglobulins in mice with and without /32- microglobulin.
  • the curves are biphasic, with phase 1 representing equilibration between the intravascular and extravascular compartments and phase 2 representing the elimination of the protein from the intravascular space.
  • the pharmacokinetic parameters are shown in Table 1. The phase 1 half lives did not differ significantly for IgGl and IgY, or between the three /32m genotypes.
  • Radiolabeled chicken IgY was cleared equally rapidly in wild type mice and in mice homozygous for the disruption in the ⁇ 2m gene ( Figure 1) .
  • the terminal half life of IgY (21-22 hours) was not significantly different than that of mouse IgGl I in /32m-/- mice (Table 1) .
  • Example 2 Generation and Screening of IgG mutants.
  • Figure 2 is a diagram showing alignment of partial amino acid sequences of immunoglobulin molecules used in Example 1 (EU numbering) .
  • Alternative amino acid residues within an isotype are shown below the most common sequence (Kabat et al., 1991, Sequences of proteins of immunological interest, 5th edn. , pp. 683, 692, NIH, Bethesda, MD) .
  • Predicted contacts (Burmeister et al., 1994, Nature: 372: 379) with FcRn are underlined. Residues required for the protection of IgG from rapid degradation and for binding to FcRn (Kim et al., 1994, Eur. J.
  • a cDNA encoding the expressed IgG Fc-binding fragment is cloned from IgG hybridoma cells.
  • Site-directed mutagenesis is used to substitute specific amino acid residues in positions 248 through 257, 308 through 314, and 429 through 436, using a commercially-available DNA primer-based site-directed mutagenesis kit (Amersham, Arlington Heights, Illinois) , according to the manufacturer's instructions.
  • the binding affinity of the mutant IgG antibodies to FcRn can be tested by immobilizing FcRn on a solid substrate e.g., a SepharoseTM bead, by standard methods .
  • An anti-IgG monoclonal antibody (of other than IgG isotype) is labelled with 125 I (Dupont, Wilmington, DE) using the IodogenTM method (Pierce Biochemical, Rockford, IL) . Free iodine is removed by gel filtration on Sephadex G-200.
  • the immobilized FcRn is contacted with 0.5 ⁇ g/ml of the test IgG plus the 125 I-labeled antibody (e.g. for 16-18 hours at 37 °C) , then washed. The amount of radioactivity remaining associated with the immobilized FcRn is measured, and the binding affinity calculated using well known methods. Alternatively, binding affinity may be evaluated using an ELISA assay known in the art.
  • FcRn-expressing cells e.g., cells transfected with a vector encoding FcRn
  • Confluent layers of FcRn-expressing cells are incubated with 0.4 ⁇ /ml 125 I-labeled native or mutant IgG to allow IgG-FcRn binding (e.g., overnight 16-18 hours at 37°C) , and washed with medium (complete RPMI, 10% FCS; Gibco, Grand Island, NY) .
  • medium complete RPMI, 10% FCS; Gibco, Grand Island, NY
  • Cells are then detached by incubation with 5 mM Na 2 EDTA in 50 mM phosphate buffer (pH 7.5) for 5 minutes.
  • the cells are pelleted and resuspended in 2 ml 2.5 mg/ml CHAPS, 0.1 M Tris-HCl (pH 8.0), 0.3 mg/ml PMSF, 25 ⁇ g/ml pepstatin and 0.1 mg/ml aprotinin and incubated for 30 minutes at room temperature.
  • the suspension is centrifuged at 12,000 x g for 30 minutes and the amount of radioactivity in pellets and supernatants determined as an indication of the level of binding of the test IgG to FcRn.
  • the test IgG can be unlabelled, and its binding detected with a labelled anti-IgG antibody as described above.
  • Example 3 Therapeutic use of IgG with increased or decreased rate of clearance.
  • mutant IgG molecules can be humanized by methods known in the art, e.g, monoclonal antibodies can be commercially humanized (Scotgene, Scotland; Oxford Molecular, Palo Alto, CA) .
  • Mutant IgG molecules can be purified using known methods, such as absorption onto immobilized Protein A or immunoaffinity chromatography. Following purification, the mutant IgG molecules of the invention or immunologically active fragments thereof can be administered to patients in a pharmaceutically acceptable excipient such as physiological saline.
  • mutant IgG molecules or other compounds of the invention can be administered by any standard route including intraperitoneally, intramuscularly, subcutaneously, or intravenously. It is expected that the preferred route of administration will be intravenous. These compounds can be administered systemically to the bloodstream.
  • dosages for any one patient depends on many factors, including the patients general health, sex, size, body surface area, age, as well as the particular compound to be administered, time and route of administration, and other drugs being administered concurrently. Dosages for compounds of the invention will vary, but a preferred dosage for intravenous administration is approximately 1 ⁇ g to 500 ⁇ g/ml/blood volume. Determination of correct dosage for a given application is well within the abilities of one of ordinary skill in the art of pharmacology. The optimal dosage may be adjusted according to the condition of the patient and response of the patient to therapy.
  • IgG carries a cytotoxic moiety
  • rapid clearance would be desired and so mutant IgGs with reduced FcRn binding are chosen.
  • nontoxic IgG molecules a decreased clearance rate is desired, and so mutant IgG molecules with increased affinity for FcRn are selected.
  • Example 4 Diagnostic use of IgG with increased rate of clearance. Labelled IgG molecules of the invention can be used diagnostically. In these situations, increased clearance of IgG is desirable so that nonspecifically bound labelled antibody is quickly removed from the body, thereby reducing background. Hybridoma strains producing IgG molecules specific for target tissue, e.g., cancer cells, are used, and the IgG molecules are mutated as described in Example 2. Testing for clearance is also conducted as in Example 2. IgG molecules with decreased binding to FcRn, compared to wild type molecules, are chosen.
  • ADDRESSEE Fish & Richardson P.C.
  • B STREET: 225 Franklin Street
  • Lys Asp Ala Leu Met lie Ser Leu Thr Pro 1 5 10

Abstract

Disclosed are mutant IgG molecules having altered amino acid sequences in the FcRn-binding region. These changes confere increased or decreased affinity for FcRn and thus, respectively, a decreased or increased rate of clearance from the systemic circulation. Such molecules can be attached to detectable labels or cytotoxic moieties for imaging tissues or for delivering cytotoxins. Also disclosed is a method for identifying IgG molecules with altered half-lives in circulation by contacting the molecules with FcRn.

Description

MODULATION OF IαG BINDING TO FcRn Background of the Invention The field of the invention is immunoglobulins. Immunoglobulin G (IgG) is used intravenously to treat a number of diseases that involve immune deficiencies, including acquired immune deficiency syndrome (AIDS) , idiopathic thrombocytopenic purpura (ITP) , Kawasaki disease, Guillaine-Barre Syndrome, and dermatomyositis. Recently, there has also been increasing use in immunosuppression in transplanted patients, and in specifically directed antibody therapy, such as monoclonal antibodies used as a form of cancer chemotherapy. Previously, immunoglobulins were extracted from pooled whole blood, but the increasing risk of infection from AIDS and the related decrease in the available blood supply precipitated increased reliance on murine monoclonal antibodies for in vivo human therapy. Initially, antibodies from such sources had problems with short half-life and inciting an immune response against the murine proteins (the HAMA response) , but both of these problems have been alleviated somewhat by the practice of humanizing the antibodies by combining the human constant region with the mouse variable region.
Although monoclonal antibodies now have a half- life similar to that of native human IgG, there are still situations where it would be desirable to have even more control over the length of time before immunoglobulins are catabolized.
This is especially true in treating immune deficiency conditions. When the concentration of IgG is increased above normal levels in the circulation, its half-life decreases. Therefore it is difficult to maintain higher-than-normal levels of the immunoglobulins during treatment, and patients require frequent injections of the antibodies. On the other hand, in situations where the antibodies are being used as a means to target a chemotherapeutic agent, such as a radionuclide or a protein toxin, to a particular tissue or cell type, the dosage is often limited by the risk of damage to the bone marrow and other normal tissues due to non-specific binding. In such cases, a shorter-than- normal half-life would be desirable.
Summary of the Invention The invention is based on the discovery that FcRn, in binding to IgG, sequesters it and protects it from degradation. FcRn is a receptor found on the intestinal surface of the neonate, and is responsible for the shuttling of maternal milk IgG from the intestinal lumen through the intestinal epithelial cell into the systemic circulation. It is now known also to be responsible for preventing IgG from being cleared from the animal's circulation. Using the guidance provided herein, one can create, using recombinant methods, an IgG molecule that has one or more amino acid additions, deletions, or substitutions (conservative or nonconservative) in the region that binds to FcRn, thereby either increasing or decreasing the molecule's affinity for FcRn. An increase in affinity would translate into the altered IgG's having a longer half-life in vivo than native IgG, while a decrease in affinity for FcRn would have the opposite effect.
Although monoclonal antibodies now have a half- life similar to that of native human IgG, there are still situations where it would be desirable to have even more control over the length of time before immunoglobulins are catabolized.
This is especially true in treating immune deficiency conditions. When the concentration of IgG is increased above normal levels in the circulation, its half-life decreases. Therefore it is difficult to maintain higher-than-normal levels of the immunoglobulins during treatment, and patients require frequent injections of the antibodies. On the other hand, in situations where the antibodies are being used as a means to target a chemotherapeutic agent, such as a radionuclide or a protein toxin, to a particular tissue or cell type, the dosage is often limited by the risk of damage to the bone marrow and other normal tissues due to non-specific binding. In such cases, a shorter-than- normal half-life would be desirable.
An IgG with an increased half-life in vivo would be useful in treating conditions such as acquired immune deficiency syndrome (AIDS) or idiopathic thrombocytopenic purpura (ITP) , where maintaining a higher-than-normal concentration of circulating IgG is desirable. A mutant IgG molecule that binds less strongly to FcRn and is therefore cleared more rapidly would be of benefit where the IgG is being used for chemotherapy or as a tumor imaging agent.
The mutated IgG of the invention would have amino acid substitutions in the FcRn-binding region only, resulting in altered half-life only, with no substantial change in overall immune function.
Also claimed is a method of removing IgG from the blood of an animal by administration of soluble FcRn, which would complex with the circulating antibody and prevent it from being sequestered by cellular FcRn. This method would be especially useful in chemotherapies, to control the ratios of tumor-bound to circulating antibodies.
Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, the preferred methods and materials are described below. All publications, patent applications, patents and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting.
Other features and advantages of the invention will be apparent from the following detailed description, and from the claims.
Brief Description of the Drawings
Figure 1 is a graph illustrating clearance of intravenously injected 125I-immunoglobulins in mice with and without /82-microglobulin. Approximately 1 x 107 counts per minute of labeled IgG was injected into the external jugular vein. Blood was collected at the time points indicated. Percent initial radioactivity = counts per minute per milligram blood at indicated time point x 100 per counts per minute per milligram blood at t0 = 1 minute after injection. Mouse IgGl is represented by the solid line, chicken IgY by a dashed line, 02m+/+ by circles, 32m+/- by triangles, and j82m-/- by diamonds; n = 5 for each group.
Figure 2 is a diagram illustrating partial amino acid sequences of IgG molecules used in this study (EU numbering) . Alternative amino acid residues within an isotype are shown below the most common sequence. Sequences are from Kabat et al., 1991, Sequences of proteins of immunological interest, 5th edn. , pg. 683, NIH, Bethesda, MD. Predicted contacts with FcRn (from Burmeister et al., 1994, Nature 372:379) are underlined. Residues for binding to FcRn (Kim et al., 1994, Eur. J. Immunol. 24:2429; Raghavan et al., 1995, Biochemistry 34:14649) are marked with an asterisk.
Figure 3 is an illustration depicting the proposed role for FcRn in protecting IgG from degradation. IgG taken up in the fluid phase binds FcRn at acidic pH in early endosomes. IgG bound to FcRn is recycled to the plasma membrane and released, whereas unbound proteins are sorted to lysosomes and degraded.
Detailed Description The altered IgG's of the invention are most readily prepared by standard reco binant DNA methods, e.g. site-directed mutagenesis or PCR. The regions of IgG to be mutated corresponds to amino acids 248 through 257, 308 through 314, and 429 through 436 of IgG. Within these regions, five particular amino acid residues have been identified as being important in FcRn binding, but others can be explored as well by using DNA primer-based site-directed mutagenesis, available commercially as a kit (Amersham, Arlington Heights, Illinois) , and well known in the art. The Amersham kit can be used according to the manufacturer's instructions in order to mutate specific residues within the FcRn-binding region.
Preliminary in vitro comparison of the binding of non-native IgG molecules relative to native IgG is done by radiolabelling the IgG molecules, incubating them with cells which express FcRn, washing the cells, and then measuring the amount of radioactivity that remains in association with the cells. Suitable cells include endothelial cells, cells (such as human embryonic kidney cell line 293) transfected with a vector encoding FcRn, or intestinal epithelial cells from suckling rats or mice. Alternatively, one could use a brush border fraction derived from such intestinal epithelial cells, prepared in accordance with standard methods (e.g., Wallace and Rees, 1980, Biochem. J. 188:9).
The mutant IgG antibodies can be tested for in vivo half life by radiolabelling with Na125I (DuPont, Wilmington, DE) using the Iodogen™ method (Pierce Biochemical, Rockford, IL) . Free iodine is removed by gel filtration on Sephadex G-25 and aggregated immunoglobulins are removed by gel filtration on Sephadex G-200. The 125I-immunoglobulin can then be diluted in 10% normal mouse serum to an injection concentration of 1 x 107 cpm / 150 μl. Anesthetized mice can be injected in the jugular vein with 150 μl of the radiolabelled immunoglobulin, and subsequently bled with capillary tubes from the retro-orbital sinus at serial time points following injection. Plasma would be collected by centrifugation and total radioactivity measured in a gamma counter and expressed as cpm/mg blood. The percentage radioactivity remaining in the blood after the last bleed would be calculated relative to the value 1 minute after injection. Protein-bound radioactivity would be measured by precipitation of the plasma in 10% TCA. The clearance curves for the various radiolabelled antibodies can then be plotted, revealing which produce antibodies with the desired characteristics. To test whether immune function is preserved, immunoprecipitation or ELISA assays can be used to ensure that the antibody does in fact complex with the antigen of interest.
For administration to human patients, the mutated immunoglobulins of the invention can be humanized by methods known in the art, e.g. , monoclonal antibodies can be commercially humanized (Scotgen, Scotland; Oxford Molecular, Palo Alto, CA) . The antibodies can then be purified using known methods, such as absorption onto immobilized Protein A or immunoaffinity chromatography. Following purification, the antibodies of the invention can be administered to patients in a pharmaceutically acceptable excipient such as physiological saline. The antibodies of the present invention can be administered by any standard route including intravenously, intraperitoneally, intramuscularly, or subcutaneously. It is expected that the preferred route of administration will be intravenous.
As is well known in the medical arts, dosages for any one patient depends on many factors, including the patients general health, sex, size, body surface area, age, as well as the particular compound to be administered, time and route of administration, and other drugs being administered concurrently. Determination of correct dosage for a given application is well within the abilities of one of ordinary skill in the art of pharmacology. The invention also includes screening methods for identifying IgG molecules with altered circulating half- lives and binding affinities relative to native IgG.
Example 1: Increased clearing in mice that lack 02- microglobulin. Animals. Mice heterozygous for the /32m gene disruption (Zijlstra et al., 1990, Nature 344:742) were mated and allowed to deliver. Tail tissue was taken from the pups for genomic DNA preparation to determine their J2m genotypes (Israel, et al., 1995, J. Immunol. 154:6246). The clearance experiments were done at 8 weeks of age. The mice were given 0.01% Nal in their drinking water one day prior to injection and throughout the period of monitoring clearance of the 125I-immunoglobulins. Preparation of 125I-immunoglobulin for injection: Mouse IgGl, IgG2a, IgG2b and IgG3 (Cappel, Durham, N.C.) and chicken IgY (Cappel) were labeled with Na125I (Dupont, Wilmington, DE) using the Iodogen™ method (Pierce Biochemical, Rockford, IL) . Free iodine was removed by gel filtration on Sephadex G-25 and aggregated immunoglobulins were removed by gel filtration on Sephadex G-200. Precipitation in 10% trichloroacetic acid (TCA) showed that at least 90% of the 125I in preparations of IgGl, IgG3, and IgY was bound to protein, and at least 80% of the radiolabel in IgG2a and IgG2b was bound to protein. The 125I-immunoglobulin was diluted in 10% normal mouse serum to achieve approximately 1 x 107 cpm/150 μl for injection. Clearance experiments: Under pentobarbitol anesthesia
(65 μg/g body weight) , the external jugular veins of 32m- /-, 32m+/~f and 32m+/+ mice were exposed and injected with approximately 150 μl of the 125I-immunoglobulin diluted in 10% normal mouse serum. The mice were bled with capillary tubes from the retro-orbital sinus at serial time points following injection, under light isotharine anesthesia. Plasma was collected by centrifugation and total radioactivity was measured in a gamma counter and expressed as cpm/mg blood. After the last bleed, the animals were killed with C02. The percentage radioactivity remaining in blood was calculated relative to the value 1 min. after injection. Protein-bound radioactivity was measured by precipitation of the plasma in 10% TCA. This protocol has been approved by the Institutional Animal Care and Use
Committee at Brandeis University.
Pharmacokinetic data analysis: The data from each animal were fitted to a double exponential model, c _ eb- 2t + ea-(kl+k2)t by a non-linear least squares method with a multiplicative error structure. The parameters kl and k2 were constrained to be positive. The area under the curve at infinity (AUC∞) , mean residence time (MRT) , terminal elimination half life (t1/2) , and the phase I half life were then calculated from a, b, kl, and k2. Means and s.e. .s for these parameters were calculated for each genotype group. Differences between the groups were tested with an analysis of variance using Gabriel's procedure to make pairwise comparisons (Gabriel, 1978, J. Amer. Statistical Assoc. 73:724).
Results: The clearance curves for radiolabeled mouse IgGl and chicken IgY are shown in Figure 1, which is a graph showing the clearance of intravenously injected 125I-labelled immunoglobulins in mice with and without /32- microglobulin. The curves are biphasic, with phase 1 representing equilibration between the intravascular and extravascular compartments and phase 2 representing the elimination of the protein from the intravascular space. The pharmacokinetic parameters are shown in Table 1. The phase 1 half lives did not differ significantly for IgGl and IgY, or between the three /32m genotypes. However, there were significant differences in the phase 2 (terminal) half lives (t1 2s) • Mouse IgGl was degraded more rapidly in /32m-/- mice than in /32m+/- or /32m+/+ littermates. Specifically, the half life was 25 hours in the /32m-/- animals compared to 5 days for the 32m+/+ mice (Fig. 1) . There was no significant difference between the clearance in heterozygous (t1 2 = 123 h) and wild type mice, suggesting that the effect on IgG catabolism was not related to the dose of the 32m gene. The radioactivity left in the serum was 95-98% precipitable by TCA at all time points (data not shown) , suggesting the radioactivity measured was indeed bound to IgG. There was little release of TCA-soluble radioactivity into the systemic circulation during the time period studied.
Radiolabeled chicken IgY was cleared equally rapidly in wild type mice and in mice homozygous for the disruption in the β2m gene (Figure 1) . The terminal half life of IgY (21-22 hours) was not significantly different than that of mouse IgGl I in /32m-/- mice (Table 1) .
Table LPharmacokinetic parameters of 125I-IgG clearance.
Figure imgf000012_0001
a = Area un er t e curve b = Mean residence time c = Terminal half life d = Mouse IgGl e = Chk en IgY
Pharmacokinetic parameters for the clearance of mouse IgGl, IgG2a, IgG2b and IgG3 compared in a separate experiment in /32m-/-, +/- and +/+ mice are shown in Table 2. The half lives of IgGl, IgG2a and IgG3 were significantly lower in 02m-/- mice than in /32m+/- or +/+ siblings. The half lives of IgG2b in mice of the three /32m genotypes were not significantly different, although degradation appeared degradation appeared more rapid in /32m-/- mice. Table 2. Pharmacokinetic parameters of mouse ^I-I G subclass clearance.
Figure imgf000013_0001
a = Area under the curve b = Mean residence time c = Terminal half life
Example 2 : Generation and Screening of IgG mutants.
Five amino acid residues (lie 253, His 310, Gin 311, His 433, and Asn 434) in the conserved portion of IgG have been identified as being important in FcRn binding. These are shown in Figure 2, which is a diagram showing alignment of partial amino acid sequences of immunoglobulin molecules used in Example 1 (EU numbering) . Alternative amino acid residues within an isotype are shown below the most common sequence (Kabat et al., 1991, Sequences of proteins of immunological interest, 5th edn. , pp. 683, 692, NIH, Bethesda, MD) . Predicted contacts (Burmeister et al., 1994, Nature: 372: 379) with FcRn are underlined. Residues required for the protection of IgG from rapid degradation and for binding to FcRn (Kim et al., 1994, Eur. J.
Immunol. 24:2429; Raghavan et al. , 1995, Biochemistry 34:14649) are marked with an asterisk. Other amino acids can be identified using known methods.
To create a mutant IgG molecule, a cDNA encoding the expressed IgG Fc-binding fragment is cloned from IgG hybridoma cells. Site-directed mutagenesis is used to substitute specific amino acid residues in positions 248 through 257, 308 through 314, and 429 through 436, using a commercially-available DNA primer-based site-directed mutagenesis kit (Amersham, Arlington Heights, Illinois) , according to the manufacturer's instructions.
The binding affinity of the mutant IgG antibodies to FcRn can be tested by immobilizing FcRn on a solid substrate e.g., a Sepharose™ bead, by standard methods . An anti-IgG monoclonal antibody (of other than IgG isotype) is labelled with 125I (Dupont, Wilmington, DE) using the Iodogen™ method (Pierce Biochemical, Rockford, IL) . Free iodine is removed by gel filtration on Sephadex G-200. The immobilized FcRn is contacted with 0.5 μg/ml of the test IgG plus the 125I-labeled antibody (e.g. for 16-18 hours at 37 °C) , then washed. The amount of radioactivity remaining associated with the immobilized FcRn is measured, and the binding affinity calculated using well known methods. Alternatively, binding affinity may be evaluated using an ELISA assay known in the art.
Further testing in a cell-based system may also be carried out. Confluent layers of FcRn-expressing cells (e.g., cells transfected with a vector encoding FcRn) are incubated with 0.4 μ/ml 125I-labeled native or mutant IgG to allow IgG-FcRn binding (e.g., overnight 16-18 hours at 37°C) , and washed with medium (complete RPMI, 10% FCS; Gibco, Grand Island, NY) . Cells are then detached by incubation with 5 mM Na2EDTA in 50 mM phosphate buffer (pH 7.5) for 5 minutes. The cells are pelleted and resuspended in 2 ml 2.5 mg/ml CHAPS, 0.1 M Tris-HCl (pH 8.0), 0.3 mg/ml PMSF, 25 μg/ml pepstatin and 0.1 mg/ml aprotinin and incubated for 30 minutes at room temperature. The suspension is centrifuged at 12,000 x g for 30 minutes and the amount of radioactivity in pellets and supernatants determined as an indication of the level of binding of the test IgG to FcRn. Alternatively, the test IgG can be unlabelled, and its binding detected with a labelled anti-IgG antibody as described above.
Final studies on in vivo clearance of the mutant IgG molecules relative to the native IgG are conducted as described in Example 1.
Example 3 : Therapeutic use of IgG with increased or decreased rate of clearance.
For administration to human patients, mutant IgG molecules can be humanized by methods known in the art, e.g, monoclonal antibodies can be commercially humanized (Scotgene, Scotland; Oxford Molecular, Palo Alto, CA) . Mutant IgG molecules can be purified using known methods, such as absorption onto immobilized Protein A or immunoaffinity chromatography. Following purification, the mutant IgG molecules of the invention or immunologically active fragments thereof can be administered to patients in a pharmaceutically acceptable excipient such as physiological saline. The mutant IgG molecules or other compounds of the invention, e.g., mutant IgG molecules linked to therapeutic agents such as cytotoxic moieties (e.g., radionuclides or toxic polypeptides such as ricin, Pseudomonas exotoxin A, and diphtheria toxin) , can be administered by any standard route including intraperitoneally, intramuscularly, subcutaneously, or intravenously. It is expected that the preferred route of administration will be intravenous. These compounds can be administered systemically to the bloodstream. As is well known in the medical arts, dosages for any one patient depends on many factors, including the patients general health, sex, size, body surface area, age, as well as the particular compound to be administered, time and route of administration, and other drugs being administered concurrently. Dosages for compounds of the invention will vary, but a preferred dosage for intravenous administration is approximately 1 μg to 500 μg/ml/blood volume. Determination of correct dosage for a given application is well within the abilities of one of ordinary skill in the art of pharmacology. The optimal dosage may be adjusted according to the condition of the patient and response of the patient to therapy. Where the IgG carries a cytotoxic moiety, as for cancer chemotherapy, rapid clearance would be desired and so mutant IgGs with reduced FcRn binding are chosen. For therapeutic use of nontoxic IgG molecules, a decreased clearance rate is desired, and so mutant IgG molecules with increased affinity for FcRn are selected.
Example 4 : Diagnostic use of IgG with increased rate of clearance. Labelled IgG molecules of the invention can be used diagnostically. In these situations, increased clearance of IgG is desirable so that nonspecifically bound labelled antibody is quickly removed from the body, thereby reducing background. Hybridoma strains producing IgG molecules specific for target tissue, e.g., cancer cells, are used, and the IgG molecules are mutated as described in Example 2. Testing for clearance is also conducted as in Example 2. IgG molecules with decreased binding to FcRn, compared to wild type molecules, are chosen.
Other Embodiments It is to be understood that while the invention has been described in conjunction with the detailed description thereof, that the foregoing description is intended to illustrate and not limit the scope of the invention, which is defined by the scope of the appended claims.
Other aspects, advantages, and modifications are within the scope of the following claims.
SEQUENCE LISTING
(1) GENERAL INFORMATION
(i) APPLICANT: Jacobowitz Israel, Esther Si ister, Neil E. (ii) TITLE OF THE INVENTION: MODULATION OF IgG
BINDING TO FcRn
(iii) NUMBER OF SEQUENCES: 15
(iv) CORRESPONDENCE ADDRESS:
(A) ADDRESSEE: Fish & Richardson P.C. (B) STREET: 225 Franklin Street
(C) CITY: Boston
(D) STATE: MA
(E) COUNTRY: USA
(F) ZIP: 02110-2804 (V) COMPUTER READABLE FORM:
(A) MEDIUM TYPE: Diskette
(B) COMPUTER: IBM Compatible
(C) OPERATING SYSTEM: DOS
(D) SOFTWARE: FastSEQ Version 2.0 (vi) CURRENT APPLICATION DATA:
(A) APPLICATION NUMBER: 00786/360002
(B) FILING DATE:
(C) CLASSIFICATION:
(vii) PRIOR APPLICATION DATA: (A) APPLICATION NUMBER: 60/031,607
(B) FILING DATE: November 27, 1996
(viii) ATTORNEY/AGENT INFORMATION:
(A) NAME: Fraser, Janis K
(B) REGISTRATION NUMBER: 34,819 (C) REFERENCE/DOCKET NUMBER: 00786/360002
(ix) TELECOMMUNICATION INFORMATION:
(A) TELEPHONE: 617-542-5070
(B) TELEFAX: 617-542-8906
(C) TELEX: (2) INFORMATION FOR SEQ ID NO:l:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 10 amino acids
(B) TYPE: amino acid (C) STRANDEDNESS: N/A
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:l:
Lys Asp Val Leu Thr lie Thr Leu Thr Pro 1 5 10
(2) INFORMATION FOR SEQ ID NO: 2:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 7 amino acids
(B) TYPE: amino acid (C) STRANDEDNESS: N/A
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 2: lie Met His Gin Asp Trp Leu 1 5
(2) INFORMATION FOR SEQ ID NO: 3:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: N/A (D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 3:
His Glu Gly Leu His Asn His His 1 5
(2) INFORMATION FOR SEQ ID NO: 4: (i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 10 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: N/A
(D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 4
Lys Asp Val Leu Met lie Ser Leu Ser Pro 1 5 10
(2) INFORMATION FOR SEQ ID NO: 5: (i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 7 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: N/A
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 5: lie Gin His Gin Asp Trp Met 1 5
(2) INFORMATION FOR SEQ ID NO: 6: (i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: N/A
(D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 6:
His Glu Gly Leu His Asn His Leu 1 5
(2) INFORMATION FOR SEQ ID NO: 7:
(i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 10 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: N/A
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 7: Lys Asp Val Leu Met lie Ser Leu Thr Pro 1 5 10
(2) INFORMATION FOR SEQ ID NO: 8:
(i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 7 amino acids (B) TYPE: amino acid
(C) STRANDEDNESS: N/A
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 8: lie Gin His Gin Asp Trp Met 1 5 (2) INFORMATION FOR SEQ ID NO: 9:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: N/A
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 9:
His Glu Gly Leu Lys Asn Tyr Tyr 1 5
(2) INFORMATION FOR SEQ ID NO: 10:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 10 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: N/A (D) TOPOLOGY: linear
( i) SEQUENCE DESCRIPTION: SEQ ID NO: 10:
Lys Asp Ala Leu Met lie Ser Leu Thr Pro 1 5 10
(2) INFORMATION FOR SEQ ID NO: 11: (i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 7 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: N/A
(D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 11: lie Gin His Gin Asp Trp Met 1 5
(2) INFORMATION FOR SEQ ID NO: 12:
(i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 8 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: N/A
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 12 His Glu Ala Leu His Asn His His 1 5
(2) INFORMATION FOR SEQ ID NO: 13:
(i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 10 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: N/A
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 13 Pro Gly Glu Leu Tyr lie Ser Leu Asp Ala 1 5 10
(2) INFORMATION FOR SEQ ID NO: 14:
(i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 7 amino acids (B) TYPE: amino acid
(C) STRANDEDNESS: N/A
(D) TOPOLOGY: linear
(Xi) SEQUENCE DESCRIPTION: SEQ ID NO: 14
Val Ser Thr Gin Asp Trp Leu 1 5
(2) INFORMATION FOR SEQ ID NO: 15:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 8 amino acids
(B) TYPE: amino acid (C) STRANDEDNESS: N/A
(D) TOPOLOGY: linear
(xi) SEQUENCE DESCRIPTION: SEQ ID NO: 15:
His Glu Ala Leu Pro Met Arg Phe 1 5

Claims

What is claimed is:
1. A non-naturally occurring IgG molecule having an altered amino acid sequence compared to native IgG, and which binds to FcRn with increased affinity relative to native IgG, the alteration comprising an addition or deletion of an amino acid within the FcRn-binding region of native IgG, or a substitution of an amino acid within said region.
2. A non-naturally occurring IgG molecule having an altered amino acid sequence compared to native IgG, and which binds to FcRn with decreased affinity relative to native IgG, the alteration comprising an addition or deletion of an amino acid within the FcRn-binding region of native IgG, or a substitution of an amino acid within said region.
3. The IgG molecule of claim 1, in which at least one of the following amino acids conserved in native IgG is substituted with another amino acid: lie 253, His 310, Gin 311, His 433, Asn 434.
4. The IgG molecule of claim 2, in which at least one of the following amino acids conserved in native IgG is substituted with another amino acid: lie 253, His 310, Gin 311, His 433, Asn 434.
5. A purified preparation of the IgG of claim 1.
6. A purified preparation of the IgG of claim 2.
7. A method of therapy comprising identifying an animal having a condition treatable with IgG and administering a therapeutically effective amount of the molecule of claim 1 to the animal.
8. A method of therapy comprising identifying an animal having a condition treatable with IgG and administering a therapeutically effective amount of the molecule of claim 2 to the animal.
9. The method of claim 7 , wherein said condition is selected from the group consisting of idiopathic thrombocytopenic purpura (ITP) , Kawasaki disease, acquired immunodeficiency syndrome (AIDS) , Guillain-Barre Syndrome, and dermatomyositis.
10. A composition comprising the molecule of claim 2 complexed to a cytotoxic moiety.
11. The composition of claim 10, wherein the cytotoxic moiety is a toxic polypeptide or a radionuclide.
12. A composition comprising the molecule of claim 2, wherein the molecule comprises a cytotoxic radionuclide.
13. A therapeutic method comprising indentifying an animal in need of treatment with an immunotoxin, and administering a therapeutically effective amount of the molecule of claim 10 to the animal.
14. A method of imaging a particular tissue in an animal, comprising
(a) providing the IgG molecule of claim 2, wherein the IgG molecule binds preferentially to said tissue and is detectably labelled; and
(b) administering the IgG molecule to the animal in an amount effective to permit the tissue to be imaged.
15. A method for identifying an IgG molecule with an altered half-life in circulation relative to native IgG, comprising
(a) contacting a molecule of FcRn with a candidate non-native IgG in vitro, and
(b) determining whether the candidate non-native IgG binds to FcRn with an affinity higher or lower than that of native IgG, wherein an affinity higher than that of native IgG indicates that the candidate non-native IgG has a half life in circulation greater than that of native IgG, and an affinity lower than that of native IgG indicates that the candidate non-native IgG has a half life in circulation shorter than that of native IgG.
16. The method of claim 15, wherein the FcRn is soluble FcRn.
17. The method of claim 15, wherein the FcRn is bound to a cell.
18. A method of increasing the rate of clearance of circulating IgG, comprising
(a) identifying an animal in need of an increased rate of clearance of circulating IgG, and
(b) administering soluble FcRn to the animal in an amount sufficient to increase the rate of clearance of circulating IgG.
19. The method of claim 18, comprising administering IgG to the animal concurrently with the soluble FcRn.
20. The method of claim 18, wherein the circulating IgG comprises IgG complexed with a cytotoxic moiety.
21. The method of claim 18, wherein the circulating IgG is a tumor imaging agent.
PCT/US1997/021437 1996-11-27 1997-11-26 MODULATION OF IgG BINDING TO FcRn WO1998023289A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US3160796P 1996-11-27 1996-11-27
US60/031,607 1996-11-27

Publications (1)

Publication Number Publication Date
WO1998023289A1 true WO1998023289A1 (en) 1998-06-04

Family

ID=21860411

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1997/021437 WO1998023289A1 (en) 1996-11-27 1997-11-26 MODULATION OF IgG BINDING TO FcRn

Country Status (1)

Country Link
WO (1) WO1998023289A1 (en)

Cited By (376)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999051642A1 (en) * 1998-04-02 1999-10-14 Genentech, Inc. Antibody variants and fragments thereof
WO2000042072A2 (en) 1999-01-15 2000-07-20 Genentech, Inc. Polypeptide variants with altered effector function
US6194551B1 (en) 1998-04-02 2001-02-27 Genentech, Inc. Polypeptide variants
US6242195B1 (en) 1998-04-02 2001-06-05 Genentech, Inc. Methods for determining binding of an analyte to a receptor
WO2002060919A2 (en) 2000-12-12 2002-08-08 Medimmune, Inc. Molecules with extended half-lives, compositions and uses thereof
US6528624B1 (en) 1998-04-02 2003-03-04 Genentech, Inc. Polypeptide variants
US6737056B1 (en) 1999-01-15 2004-05-18 Genentech, Inc. Polypeptide variants with altered effector function
WO2005037867A1 (en) * 2003-10-15 2005-04-28 Pdl Biopharma, Inc. ALTERATION OF Fc-FUSION PROTEIN SERUM HALF-LIVES BY MUTAGENESIS OF POSITIONS 250, 314 AND/OR 428 OF THE HEAVY CHAIN CONSTANT REGION OF IG
WO2006089133A2 (en) 2005-02-15 2006-08-24 Duke University Anti-cd19 antibodies and uses in oncology
US7132100B2 (en) 2002-06-14 2006-11-07 Medimmune, Inc. Stabilized liquid anti-RSV antibody formulations
US7183387B1 (en) 1999-01-15 2007-02-27 Genentech, Inc. Polypeptide variants with altered effector function
WO2006053301A3 (en) * 2004-11-12 2007-04-05 Xencor Inc Fc variants with altered binding to fcrn
US7217797B2 (en) 2002-10-15 2007-05-15 Pdl Biopharma, Inc. Alteration of FcRn binding affinities or serum half-lives of antibodies by mutagenesis
WO2007147090A2 (en) 2006-06-14 2007-12-21 Macrogenics, Inc. Methods for the treatment of autoimmune disorders using monoclonal antibodies with reduced toxicity
US7355008B2 (en) 2003-01-09 2008-04-08 Macrogenics, Inc. Identification and engineering of antibodies with variant Fc regions and methods of using same
AU2008201419A1 (en) * 2000-12-12 2008-04-24 Board Of Regents, The University Of Texas System Molecules with extended half-lives, compositions and uses thereof
US7365168B2 (en) 2002-10-15 2008-04-29 Pdl Biopharma, Inc. Alteration of FcRn binding affinities or serum half-lives of antibodies by mutagenesis
US7371381B2 (en) 2003-12-12 2008-05-13 Amgen Inc. Anti-galanin antibodies and uses thereof
US7416726B2 (en) 2000-04-13 2008-08-26 The Rockefeller University Enhancement of antibody-mediated immune responses
US7425618B2 (en) 2002-06-14 2008-09-16 Medimmune, Inc. Stabilized anti-respiratory syncytial virus (RSV) antibody formulations
WO2008136694A1 (en) 2007-05-04 2008-11-13 Technophage, Investigação E Desenvolvimento Em Biotecnologia, Sa Engineered rabbit antibody variable domains and uses thereof
US7632497B2 (en) 2004-11-10 2009-12-15 Macrogenics, Inc. Engineering Fc Antibody regions to confer effector function
US7659374B2 (en) 2004-08-16 2010-02-09 Medimmune, Llc Eph receptor Fc variants with enhanced antibody dependent cell-mediated cytotoxicity activity
US7658921B2 (en) 2000-12-12 2010-02-09 Medimmune, Llc Molecules with extended half-lives, compositions and uses thereof
WO2010015608A1 (en) 2008-08-05 2010-02-11 Novartis Ag Compositions and methods for antibodies targeting complement protein c5
US7662925B2 (en) 2002-03-01 2010-02-16 Xencor, Inc. Optimized Fc variants and methods for their generation
WO2010027364A1 (en) 2008-09-07 2010-03-11 Glyconex Inc. Anti-extended type i glycosphingolipid antibody, derivatives thereof and use
US7700097B2 (en) 2003-06-27 2010-04-20 Biogen Idec Ma Inc. Purification and preferential synthesis of binding molecules
WO2010056804A1 (en) 2008-11-12 2010-05-20 Medimmune, Llc Antibody formulation
US7740847B2 (en) 2004-08-04 2010-06-22 Applied Molecular Evolution, Inc. Variant Fc regions
WO2010070346A2 (en) 2008-12-18 2010-06-24 Medimmune Limited BINDING MEMBERS FOR INTERLEUKIN-4 RECEPTOR ALPHA (IL-4Ra) - 836
WO2010072740A2 (en) 2008-12-23 2010-07-01 Astrazeneca Ab TARGETED BINDING AGENTS DIRECTED TO α5β1 AND USES THEREOF
WO2010078526A1 (en) 2008-12-31 2010-07-08 Biogen Idec Ma Inc. Anti-lymphotoxin antibodies
EP2221316A1 (en) 2005-05-05 2010-08-25 Duke University Anti-CD19 antibody therapy for autoimmune disease
US7786270B2 (en) 2006-05-26 2010-08-31 Macrogenics, Inc. Humanized FcγRIIB-specific antibodies and methods of use thereof
US7863419B2 (en) 2003-08-22 2011-01-04 Biogen Idec Ma Inc. Antibodies having altered effector function and methods for making the same
US7867734B2 (en) 2004-10-26 2011-01-11 Chugai Seiyaku Kabushiki Kaisha Anti-glypican 3 antibody having modified sugar chain
US7871613B2 (en) 2004-08-24 2011-01-18 Chugai Seiyaku Kabushiki Kaisha Adjuvant therapy with the use of anti-glypican 3 antibody
JP2011502126A (en) * 2007-10-31 2011-01-20 ゼンコア インコーポレイテッド Fc variant having mutant binding to FcRn
WO2011020024A2 (en) 2009-08-13 2011-02-17 The Johns Hopkins University Methods of modulating immune function
EP2292264A2 (en) 2003-07-24 2011-03-09 Innate Pharma Methods and compositions for increasing the efficiency of therapeutic antibodies using NK cell potentiating compounds
JP2011507963A (en) * 2007-12-26 2011-03-10 ゼンコア インコーポレイテッド Fc variant having mutant binding to FcRn
EP2298806A1 (en) 2002-10-16 2011-03-23 Purdue Pharma L.P. Antibodies that bind cell-associated CA 125/0722P and methods of use thereof
US7919086B2 (en) 2004-07-09 2011-04-05 Chugai Seiyaku Kabushiki Kaisha Anti-glypican 3 antibody
WO2011044368A1 (en) 2009-10-07 2011-04-14 Macrogenics, Inc. Fc region-containing polypeptides that exhibit improved effector function due to alterations of the extent of fucosylation, and methods for their use
EP2316487A1 (en) 2003-04-11 2011-05-04 MedImmune, LLC Recombinant IL-9 antibodies & uses thereof
WO2011053982A2 (en) 2009-11-02 2011-05-05 University Of Washington Therapeutic nuclease compositions and methods
US7973136B2 (en) 2005-10-06 2011-07-05 Xencor, Inc. Optimized anti-CD30 antibodies
US8008443B2 (en) 2005-04-26 2011-08-30 Medimmune, Llc Modulation of antibody effector function by hinge domain engineering
EP2371389A2 (en) 2002-08-14 2011-10-05 MacroGenics, Inc. FcgammaRIIB-specific antibodies and methods of use thereof
US8039592B2 (en) 2002-09-27 2011-10-18 Xencor, Inc. Optimized Fc variants and methods for their generation
WO2011138392A1 (en) 2010-05-06 2011-11-10 Novartis Ag Compositions and methods of use for therapeutic low density lipoprotein -related protein 6 (lrp6) antibodies
WO2011138391A1 (en) 2010-05-06 2011-11-10 Novartis Ag Compositions and methods of use for therapeutic low density lipoprotein - related protein 6 (lrp6) multivalent antibodies
AU2011253690A1 (en) * 2000-12-12 2011-12-22 Board Of Regents, The University Of Texas System Molecules with extended half-lives, compositions and uses thereof
US8084582B2 (en) 2003-03-03 2011-12-27 Xencor, Inc. Optimized anti-CD20 monoclonal antibodies having Fc variants
WO2012006633A1 (en) 2010-07-09 2012-01-12 Biogen Idec Hemophilia Inc. Chimeric clotting factors
US8101720B2 (en) 2004-10-21 2012-01-24 Xencor, Inc. Immunoglobulin insertions, deletions and substitutions
WO2012022814A1 (en) 2010-08-20 2012-02-23 Novartis Ag Antibodies for epidermal growth factor receptor 3 (her3)
US8124731B2 (en) 2002-03-01 2012-02-28 Xencor, Inc. Optimized Fc variants and methods for their generation
US8188231B2 (en) 2002-09-27 2012-05-29 Xencor, Inc. Optimized FC variants
US8187593B2 (en) 2002-08-14 2012-05-29 Macrogenics, Inc. FcγRIIB specific antibodies and methods of use thereof
WO2012069466A1 (en) 2010-11-24 2012-05-31 Novartis Ag Multispecific molecules
WO2012083370A1 (en) 2010-12-22 2012-06-28 Cephalon Australia Pty Ltd Modified antibody with improved half-life
EP2505209A1 (en) 2006-06-26 2012-10-03 MacroGenics, Inc. Fcgamma-RIIB-specific antibodies and methods of the use thereof
WO2012145493A1 (en) 2011-04-20 2012-10-26 Amplimmune, Inc. Antibodies and other molecules that bind b7-h1 and pd-1
US8298533B2 (en) 2008-11-07 2012-10-30 Medimmune Limited Antibodies to IL-1R1
WO2012149440A2 (en) 2011-04-29 2012-11-01 University Of Washington Therapeutic nuclease compositions and methods
US8309690B2 (en) 2005-07-01 2012-11-13 Medimmune, Llc Integrated approach for generating multidomain protein therapeutics
US8318907B2 (en) 2004-11-12 2012-11-27 Xencor, Inc. Fc variants with altered binding to FcRn
WO2012172495A1 (en) 2011-06-14 2012-12-20 Novartis Ag Compositions and methods for antibodies targeting tem8
EP2540741A1 (en) 2006-03-06 2013-01-02 Aeres Biomedical Limited Humanized anti-CD22 antibodies and their use in treatment of oncology, transplantation and autoimmune disease
WO2013012733A1 (en) 2011-07-15 2013-01-24 Biogen Idec Ma Inc. Heterodimeric fc regions, binding molecules comprising same, and methods relating thereto
WO2013025779A1 (en) 2011-08-15 2013-02-21 Amplimmune, Inc. Anti-b7-h4 antibodies and their uses
US8388965B2 (en) 2007-10-15 2013-03-05 Sanofi Antibodies that bind IL-4 and/or IL-13 and their uses
US8388955B2 (en) 2003-03-03 2013-03-05 Xencor, Inc. Fc variants
US8394374B2 (en) 2006-09-18 2013-03-12 Xencor, Inc. Optimized antibodies that target HM1.24
WO2013039954A1 (en) 2011-09-14 2013-03-21 Sanofi Anti-gitr antibodies
EP2573114A1 (en) 2005-08-10 2013-03-27 MacroGenics, Inc. Identification and engineering of antibodies with variant Fc regions and methods of using same
US8409568B2 (en) 2005-10-14 2013-04-02 Medimmune, Llc Mutant antibody Fc domains and fusion proteins thereof
WO2013067355A1 (en) 2011-11-04 2013-05-10 Novartis Ag Low density lipoprotein-related protein 6 (lrp6) - half life extender constructs
WO2013085972A1 (en) 2011-12-05 2013-06-13 X-Body, Inc. Pdgf receptor beta binding polypeptides
WO2013084147A2 (en) 2011-12-05 2013-06-13 Novartis Ag Antibodies for epidermal growth factor receptor 3 (her3)
WO2013084148A2 (en) 2011-12-05 2013-06-13 Novartis Ag Antibodies for epidermal growth factor receptor 3 (her3) directed to domain ii of her3
EP2604628A2 (en) 2007-12-21 2013-06-19 Medimmune Limited Binding members for interleukin-4 receptor alpha (IL-4R) - 173
WO2013093762A1 (en) 2011-12-21 2013-06-27 Novartis Ag Compositions and methods for antibodies targeting factor p
US8524867B2 (en) 2006-08-14 2013-09-03 Xencor, Inc. Optimized antibodies that target CD19
US8530627B2 (en) 2002-08-14 2013-09-10 Macrogenics, Inc. FcγRIIB specific antibodies and methods of use thereof
US8546543B2 (en) 2004-11-12 2013-10-01 Xencor, Inc. Fc variants that extend antibody half-life
WO2013148296A1 (en) 2012-03-28 2013-10-03 Sanofi Antibodies to bradykinin b1 receptor ligands
WO2013169657A1 (en) 2012-05-07 2013-11-14 Sanofi Methods for preventing biofilm formation
WO2013175276A1 (en) 2012-05-23 2013-11-28 Argen-X B.V Il-6 binding molecules
WO2013185113A1 (en) 2012-06-08 2013-12-12 Biogen Idec Ma Inc. Procoagulant compounds
WO2013185114A2 (en) 2012-06-08 2013-12-12 Biogen Idec Ma Inc. Chimeric clotting factors
US8618252B2 (en) 2003-11-12 2013-12-31 Biogen Idec Ma Inc. Neonatal Fc receptor (FcRn)-binding polypeptide variants, dimeric Fc binding proteins and methods related thereto
US8647625B2 (en) 2004-07-26 2014-02-11 Biogen Idec Ma Inc. Anti-CD154 antibodies
US8647622B2 (en) 2007-08-29 2014-02-11 Sanofi Humanized anti-CXCR5 antibodies, derivatives thereof and their use
EP2703011A2 (en) 2007-05-07 2014-03-05 MedImmune, LLC Anti-icos antibodies and their use in treatment of oncology, transplantation and autoimmune disease
WO2014074905A1 (en) 2012-11-08 2014-05-15 Eleven Biotherapeutics, Inc. Il-6 antagonists and uses thereof
WO2014084859A1 (en) 2012-11-30 2014-06-05 Novartis Ag Molecules and methods for modulating tmem16a activities
WO2014089111A1 (en) 2012-12-05 2014-06-12 Novartis Ag Compositions and methods for antibodies targeting epo
WO2014100483A1 (en) 2012-12-19 2014-06-26 Amplimmune, Inc. Anti-human b7-h4 antibodies and their uses
WO2014100823A1 (en) 2012-12-21 2014-06-26 Amplimmune, Inc. Anti-h7cr antibodies
US8775090B2 (en) 2008-12-12 2014-07-08 Medimmune, Llc Crystals and structure of a human IgG Fc variant with enhanced FcRn binding
US8795667B2 (en) 2007-12-19 2014-08-05 Macrogenics, Inc. Compositions for the prevention and treatment of smallpox
WO2014127215A1 (en) 2013-02-15 2014-08-21 Biogen Idec Ma Inc. Optimized factor viii gene
WO2014160958A1 (en) 2013-03-29 2014-10-02 Alexion Pharmaceuticals, Inc. Compositions and methods for increasing the serum half-life of a therapeutic agent targeting complement c5
WO2014159239A2 (en) 2013-03-14 2014-10-02 Novartis Ag Antibodies against notch 3
US8852608B2 (en) 2009-02-02 2014-10-07 Medimmune, Llc Antibodies against and methods for producing vaccines for respiratory syncytial virus
WO2014164503A1 (en) 2013-03-11 2014-10-09 Genzyme Corporation Hyperglycosylated binding polypeptides
WO2014190356A2 (en) 2013-05-24 2014-11-27 Amplimmune, Inc. Anti-b7-h5 antibodies and their uses
US8906844B2 (en) 2007-08-09 2014-12-09 Biogen Idec Hemophilia Inc. Immunomodulatory peptides
WO2014205302A2 (en) 2013-06-21 2014-12-24 Novartis Ag Lectin-like oxidized ldl receptor1 antibodies and methods of use
WO2014205300A2 (en) 2013-06-21 2014-12-24 Novartis Ag Lectin-like oxidized ldl receptor1 antibodies and methods of use
US8937158B2 (en) 2003-03-03 2015-01-20 Xencor, Inc. Fc variants with increased affinity for FcγRIIc
US8946387B2 (en) 2002-08-14 2015-02-03 Macrogenics, Inc. FcγRIIB specific antibodies and methods of use thereof
US8951517B2 (en) 2003-01-09 2015-02-10 Macrogenics, Inc. Identification and engineering of antibodies with variant Fc regions and methods of using same
WO2015023891A2 (en) 2013-08-14 2015-02-19 Biogen Idec Ma Inc. Factor viii-xten fusions and uses thereof
US8968730B2 (en) 2002-08-14 2015-03-03 Macrogenics Inc. FcγRIIB specific antibodies and methods of use thereof
US8969526B2 (en) 2011-03-29 2015-03-03 Roche Glycart Ag Antibody Fc variants
US8980273B1 (en) 2014-07-15 2015-03-17 Kymab Limited Method of treating atopic dermatitis or asthma using antibody to IL4RA
US8986691B1 (en) 2014-07-15 2015-03-24 Kymab Limited Method of treating atopic dermatitis or asthma using antibody to IL4RA
US8993730B2 (en) 2008-04-02 2015-03-31 Macrogenics, Inc. BCR-complex-specific antibodies and methods of using same
US9012603B2 (en) 2006-02-17 2015-04-21 Biogen Idec Hemophilia Inc. Peptides that block the binding of IgG to FcRn
WO2015066557A1 (en) 2013-10-31 2015-05-07 Resolve Therapeutics, Llc Therapeutic nuclease molecules with altered glycosylation and methods
US9040041B2 (en) 2005-10-03 2015-05-26 Xencor, Inc. Modified FC molecules
US9051373B2 (en) 2003-05-02 2015-06-09 Xencor, Inc. Optimized Fc variants
US9079949B1 (en) 2014-03-07 2015-07-14 Alexion Pharmaceuticals, Inc. Anti-C5 antibodies having improved pharmacokinetics
WO2015106052A1 (en) 2014-01-10 2015-07-16 Biogen Ma Inc. Factor viii chimeric proteins and uses thereof
US9102739B2 (en) 2005-10-14 2015-08-11 Chugai Seiyaku Kabushiki Kaisha Anti-glypican-3 antibody
WO2015143271A1 (en) 2014-03-21 2015-09-24 X-Body, Inc. Bi-specific antigen-binding polypeptides
US9150656B2 (en) 2010-03-04 2015-10-06 Macrogenics, Inc. Antibodies reactive with B7-H3, immunologically active fragments thereof and uses thereof
EP2927244A1 (en) 2008-09-19 2015-10-07 MedImmune, LLC Antibodies directed to DLL4 and uses thereof
WO2015175874A2 (en) 2014-05-16 2015-11-19 Medimmune, Llc Molecules with altered neonate fc receptor binding having enhanced therapeutic and diagnostic properties
WO2015184099A1 (en) 2014-05-28 2015-12-03 4-Antibody Ag Anti-gitr antibodies and methods of use thereof
US9243069B2 (en) 2008-04-02 2016-01-26 Macrogenics, Inc. HER2/neu-specific antibodies and methods of using the same
WO2016020882A2 (en) 2014-08-07 2016-02-11 Novartis Ag Angiopoetin-like 4 (angptl4) antibodies and methods of use
WO2016020880A2 (en) 2014-08-07 2016-02-11 Novartis Ag Angiopoietin-like 4 antibodies and methods of use
US9284375B2 (en) 2005-04-15 2016-03-15 Macrogenics, Inc. Covalent diabodies and uses thereof
US9283274B2 (en) 2009-10-06 2016-03-15 Medimmune Limited RSV specific binding molecule
US9296816B2 (en) 2005-04-15 2016-03-29 Macrogenics, Inc. Covalent diabodies and uses thereof
WO2016046301A1 (en) 2014-09-26 2016-03-31 Bayer Pharma Aktiengesellschaft Stabilized adrenomedullin derivatives and use thereof
WO2016057846A1 (en) 2014-10-08 2016-04-14 Novartis Ag Compositions and methods of use for augmented immune response and cancer therapy
WO2016061286A2 (en) 2014-10-14 2016-04-21 Halozyme, Inc. Compositions of adenosine deaminase-2 (ada2), variants thereof and methods of using same
US9321831B2 (en) 2007-06-01 2016-04-26 Medimmune Limited RSV-specific binding molecules and means for producing them
WO2016081748A2 (en) 2014-11-21 2016-05-26 Bristol-Myers Squibb Company Antibodies against cd73 and uses thereof
WO2016094834A2 (en) 2014-12-12 2016-06-16 Alexion Pharmaceuticals, Inc. A method for treating a complement mediated disorder caused by an infectious agent in a patient
WO2016098079A2 (en) 2014-12-19 2016-06-23 Novartis Ag Compositions and methods for antibodies targeting bmp6
US9376495B2 (en) 2011-05-21 2016-06-28 Macrogenics, Inc. Deimmunized serum-binding domains and their use in extending serum half-life
US9376672B2 (en) 2009-08-24 2016-06-28 Amunix Operating Inc. Coagulation factor IX compositions and methods of making and using same
WO2016106221A1 (en) 2014-12-22 2016-06-30 The Rockefeller University Anti-mertk agonistic antibodies and uses thereof
WO2016115345A1 (en) 2015-01-14 2016-07-21 The Brigham And Women's Hospital, Treatment of cancer with anti-lap monoclonal antibodies
WO2016123454A1 (en) 2015-01-29 2016-08-04 Board Of Trustees Of Miching State University Cryptic polypeptides and uses thereof
US9441049B2 (en) 2010-03-04 2016-09-13 Macrogenics, Inc. Antibodies reactive with B7-H3 and uses thereof
EP3072525A1 (en) 2007-05-14 2016-09-28 MedImmune, LLC Methods of reducing basophil levels
EP3073267A1 (en) 2004-09-21 2016-09-28 Medimmune, Inc. Antibodies against and methods for producing vaccines for respiratory syncytial virus
US9475881B2 (en) 2010-01-19 2016-10-25 Xencor, Inc. Antibody variants with enhanced complement activity
US9487587B2 (en) 2013-03-05 2016-11-08 Macrogenics, Inc. Bispecific molecules that are immunoreactive with immune effector cells of a companion animal that express an activating receptor and cells that express B7-H3 and uses thereof
US9486507B2 (en) 2011-06-10 2016-11-08 Biogen Ma Inc. Pro-coagulant compounds and methods of use thereof
WO2016196228A1 (en) 2015-05-29 2016-12-08 Bristol-Myers Squibb Company Antibodies against ox40 and uses thereof
WO2016193872A2 (en) 2015-06-05 2016-12-08 Novartis Ag Antibodies targeting bone morphogenetic protein 9 (bmp9) and methods therefor
WO2016207858A1 (en) 2015-06-26 2016-12-29 Novartis Ag Factor xi antibodies and methods of use
WO2017004016A1 (en) 2015-06-29 2017-01-05 The Rockefeller University Antibodies to cd40 with enhanced agonist activity
WO2017019846A1 (en) 2015-07-30 2017-02-02 Macrogenics, Inc. Pd-1-binding molecules and methods use thereof
WO2017021893A1 (en) 2015-08-03 2017-02-09 Novartis Ag Methods of treating fgf21-associated disorders
WO2017040790A1 (en) 2015-09-01 2017-03-09 Agenus Inc. Anti-pd-1 antibodies and methods of use thereof
US9592289B2 (en) 2012-03-26 2017-03-14 Sanofi Stable IgG4 based binding agent formulations
WO2017042701A1 (en) 2015-09-09 2017-03-16 Novartis Ag Thymic stromal lymphopoietin (tslp)-binding antibodies and methods of using the antibodies
WO2017046746A1 (en) 2015-09-15 2017-03-23 Acerta Pharma B.V. Therapeutic combinations of a btk inhibitor and a gitr binding molecule, a 4-1bb agonist, or an ox40 agonist
WO2017077391A2 (en) 2015-11-04 2017-05-11 Astrazeneca Ab Dipeptidyl peptidase-4 and periostin as predictors of clinical response to eosinophil-targeted therapeutic agents in eosinophilic diseases
WO2017093947A1 (en) 2015-12-04 2017-06-08 Novartis Ag Antibody cytokine engrafted compositions and methods of use for immunoregulation
WO2017106061A1 (en) 2015-12-14 2017-06-22 Macrogenics, Inc. Bispecific molecules having immunoreactivity with pd-1 and ctla-4, and methods of use thereof
WO2017103895A1 (en) 2015-12-18 2017-06-22 Novartis Ag Antibodies targeting cd32b and methods of use thereof
US9695233B2 (en) 2012-07-13 2017-07-04 Roche Glycart Ag Bispecific anti-VEGF/anti-ANG-2 antibodies and their use in the treatment of ocular vascular diseases
US9708408B2 (en) 2006-12-08 2017-07-18 Macrogenics, Inc. Methods for the treatment of disease using immunoglobulins having Fc Regions with altered affinities for FcγRactivating and FcγRinhibiting
WO2017122130A1 (en) 2016-01-11 2017-07-20 Novartis Ag Immune-stimulating humanized monoclonal antibodies against human interleukin-2, and fusion proteins thereof
US9714282B2 (en) 2003-09-26 2017-07-25 Xencor, Inc. Optimized Fc variants and methods for their generation
WO2017125897A1 (en) 2016-01-21 2017-07-27 Novartis Ag Multispecific molecules targeting cll-1
WO2017136358A1 (en) 2016-02-01 2017-08-10 Bioverativ Therapeutics Inc. Optimized factor viii genes
US9737599B2 (en) 2006-06-26 2017-08-22 Macrogenics, Inc. Combination of FcγRIIB-specific antibodies and CD20-specific antibodies and methods of use thereof
WO2017142928A1 (en) 2016-02-17 2017-08-24 Macrogenics, Inc. Ror1-binding molecules, and methods of use thereof
WO2017152085A1 (en) 2016-03-04 2017-09-08 Bristol-Myers Squibb Company Combination therapy with anti-cd73 antibodies
WO2017151176A1 (en) 2016-03-04 2017-09-08 The Rockefeller University Antibodies to cd40 with enhanced agonist activity
US9790268B2 (en) 2012-09-12 2017-10-17 Genzyme Corporation Fc containing polypeptides with altered glycosylation and reduced effector function
WO2017180813A1 (en) 2016-04-15 2017-10-19 Macrogenics, Inc. Novel b7-h3 binding molecules, antibody drug conjugates thereof and methods of use thereof
WO2017189724A1 (en) 2016-04-27 2017-11-02 Novartis Ag Antibodies against growth differentiation factor 15 and uses thereof
US9822181B2 (en) 2013-08-23 2017-11-21 Macrogenics, Inc. Bi-specific monovalent diabodies that are capable of binding CD123 and CD3, and uses thereof
WO2017205721A1 (en) 2016-05-27 2017-11-30 Agenus Inc. Anti-tim-3 antibodies and methods of use thereof
US9845363B2 (en) 2013-08-13 2017-12-19 Sanofi Antibodies to plasminogen activator inhibitor-1 (PAI-1) and uses thereof
WO2017216724A1 (en) 2016-06-15 2017-12-21 Novartis Ag Methods for treating disease using inhibitors of bone morphogenetic protein 6 (bmp6)
WO2018005954A2 (en) 2016-07-01 2018-01-04 Resolve Therapeutics, Llc Optimized binuclease fusions and methods
EP3279215A1 (en) 2009-11-24 2018-02-07 MedImmune Limited Targeted binding agents against b7-h1
US9889197B2 (en) 2005-04-15 2018-02-13 Macrogenics, Inc. Covalently-associated diabody complexes that possess charged coil domains and that are capable of enhanced binding to serum albumin
US9908938B2 (en) 2013-03-14 2018-03-06 Macrogenics, Inc. Bispecific molecules that are immunoreactive with immune effector cells that express an activating receptor and an antigen expressed by a cell infected by a virus and uses thereof
WO2018057735A1 (en) 2016-09-21 2018-03-29 Nextcure, Inc. Antibodies for siglec-15 and methods of use thereof
US9932400B2 (en) 2013-08-23 2018-04-03 Macrogenics, Inc. Bi-specific monovalent diabodies that are capable of binding to gpA33 and CD3, and uses thereof
WO2018071500A1 (en) 2016-10-11 2018-04-19 Agenus Inc. Anti-lag-3 antibodies and methods of use thereof
WO2018075758A1 (en) 2016-10-19 2018-04-26 Alexion Pharmaceuticals, Inc. A method of quantitating unbound c5 in a sample
US9963510B2 (en) 2005-04-15 2018-05-08 Macrogenics, Inc. Covalent diabodies and uses thereof
US9975966B2 (en) 2014-09-26 2018-05-22 Chugai Seiyaku Kabushiki Kaisha Cytotoxicity-inducing theraputic agent
WO2018102760A1 (en) 2016-12-02 2018-06-07 Bioverativ Therapeutics Inc. Methods of inducing immune tolerance to clotting factors
WO2018102743A1 (en) 2016-12-02 2018-06-07 Bioverativ Therapeutics Inc. Methods of treating hemophilic arthropathy using chimeric clotting factors
WO2018106864A1 (en) 2016-12-07 2018-06-14 Agenus Inc. Antibodies and methods of use thereof
WO2018106862A1 (en) 2016-12-07 2018-06-14 Agenus Inc. Anti-ctla-4 antibodies and methods of use thereof
WO2018116267A2 (en) 2016-12-23 2018-06-28 Novartis Ag Methods of treatment with anti-factor xi/xia antibodies
WO2018119196A1 (en) 2016-12-23 2018-06-28 Immunogen, Inc. Immunoconjugates targeting adam9 and methods of use thereof
WO2018116255A1 (en) 2016-12-23 2018-06-28 Novartis Ag Factor xi antibodies and methods of use
WO2018129332A1 (en) 2017-01-06 2018-07-12 Iovance Biotherapeutics, Inc. Expansion of tumor infiltrating lymphocytes (tils) with tumor necrosis factor receptor superfamily (tnfrsf) agonists and therapeutic combinations of tils and tnfrsf agonists
WO2018129336A1 (en) 2017-01-06 2018-07-12 Iovance Biotherapeutics, Inc. Expansion of tumor infiltrating lymphocytes with potassium channel agonists and therapeutic uses thereof
WO2018128939A1 (en) 2017-01-05 2018-07-12 Gensun Biopharma Inc. Checkpoint regulator antagonists
US10023628B2 (en) 2012-07-06 2018-07-17 Bioverativ Therapeutics Inc. Cell line expressing single chain factor VIII polypeptides and uses thereof
WO2018146594A1 (en) 2017-02-08 2018-08-16 Novartis Ag Fgf21 mimetic antibodies and uses thereof
US10064952B2 (en) 2014-10-09 2018-09-04 Genzyme Corporation Glycoengineered antibody drug conjugates
WO2018187613A2 (en) 2017-04-07 2018-10-11 Bristol-Myers Squibb Company Anti-icos agonist antibodies and uses thereof
US10100121B2 (en) 2012-06-27 2018-10-16 Amgen Inc. Anti-mesothelin binding proteins
WO2018191502A2 (en) 2017-04-13 2018-10-18 Agenus Inc. Anti-cd137 antibodies and methods of use thereof
WO2018193427A1 (en) 2017-04-21 2018-10-25 Staten Biotechnology B.V. Anti-apoc3 antibodies and methods of use thereof
WO2018200422A1 (en) 2017-04-24 2018-11-01 Alexion Pharmaceuticals, Inc. Antibody immune cell inhibitor fusion proteins
WO2018204363A1 (en) 2017-05-01 2018-11-08 Agenus Inc. Anti-tigit antibodies and methods of use thereof
WO2018209115A1 (en) 2017-05-10 2018-11-15 Iovance Biotherapeutics, Inc. Expansion of tumor infiltrating lymphocytes from liquid tumors and therapeutic uses thereof
US10138291B2 (en) 2012-07-11 2018-11-27 Bioverativ Therapeutics Inc. Factor VIII complex with XTEN and von Willebrand Factor protein, and uses thereof
WO2018215937A1 (en) 2017-05-24 2018-11-29 Novartis Ag Interleukin-7 antibody cytokine engrafted proteins and methods of use in the treatment of cancer
WO2018215936A1 (en) 2017-05-24 2018-11-29 Novartis Ag Antibody-cytokine engrafted proteins and methods of use in the treatment of cancer
WO2018218056A1 (en) 2017-05-25 2018-11-29 Birstol-Myers Squibb Company Antibodies comprising modified heavy constant regions
WO2018215938A1 (en) 2017-05-24 2018-11-29 Novartis Ag Antibody-cytokine engrafted proteins and methods of use
WO2018215935A1 (en) 2017-05-24 2018-11-29 Novartis Ag Antibody-cytokine engrafted proteins and methods of use for immune related disorders
WO2018222685A1 (en) 2017-05-31 2018-12-06 Stcube & Co., Inc. Methods of treating cancer using antibodies and molecules that immunospecifically bind to btn1a1
WO2018222689A1 (en) 2017-05-31 2018-12-06 Stcube & Co., Inc. Antibodies and molecules that immunospecifically bind to btn1a1 and the therapeutic uses thereof
WO2018226671A1 (en) 2017-06-06 2018-12-13 Stcube & Co., Inc. Methods of treating cancer using antibodies and molecules that bind to btn1a1 or btn1a1-ligands
WO2018229715A1 (en) 2017-06-16 2018-12-20 Novartis Ag Compositions comprising anti-cd32b antibodies and methods of use thereof
WO2019032898A1 (en) 2017-08-09 2019-02-14 Bioverativ Therapeutics Inc. Nucleic acid molecules and uses thereof
WO2019040780A1 (en) 2017-08-25 2019-02-28 Five Prime Therapeutics Inc. B7-h4 antibodies and methods of use thereof
WO2019040674A1 (en) 2017-08-22 2019-02-28 Sanabio, Llc Soluble interferon receptors and uses thereof
EP3456736A1 (en) 2017-09-19 2019-03-20 Tillotts Pharma Ag Antibody variants
EP3456737A1 (en) 2017-09-19 2019-03-20 Tillotts Pharma Ag Antibody variants
WO2019081983A1 (en) 2017-10-25 2019-05-02 Novartis Ag Antibodies targeting cd32b and methods of use thereof
WO2019087115A1 (en) 2017-10-31 2019-05-09 Staten Biotechnology B.V. Anti-apoc3 antibodies and methods of use thereof
WO2019103857A1 (en) 2017-11-22 2019-05-31 Iovance Biotherapeutics, Inc. Expansion of peripheral blood lymphocytes (pbls) from peripheral blood
WO2019118873A2 (en) 2017-12-15 2019-06-20 Iovance Biotherapeutics, Inc. Systems and methods for determining the beneficial administration of tumor infiltrating lymphocytes, and methods of use thereof and beneficial administration of tumor infiltrating lymphocytes, and methods of use thereof
EP3505179A1 (en) 2012-01-12 2019-07-03 Bioverativ Therapeutics Inc. Chimeric factor viii polypeptides and uses thereof
WO2019133747A1 (en) 2017-12-27 2019-07-04 Bristol-Myers Squibb Company Anti-cd40 antibodies and uses thereof
WO2019129054A1 (en) 2017-12-27 2019-07-04 信达生物制药(苏州)有限公司 Triabody, preparation method and use thereof
US10344092B2 (en) 2013-08-09 2019-07-09 Macrogenics, Inc. Bi-specific monovalent Fc diabodies that are capable of binding CD32B and CD79b and uses thereof
US10358497B2 (en) 2015-09-29 2019-07-23 Amgen Inc. Methods of treating cardiovascular disease with an ASGR inhibitor
US10370430B2 (en) 2012-02-15 2019-08-06 Bioverativ Therapeutics Inc. Recombinant factor VIII proteins
WO2019152692A1 (en) 2018-02-01 2019-08-08 Bioverativ Therapeutics, Inc. Use of lentiviral vectors expressing factor viii
WO2019160829A1 (en) 2018-02-13 2019-08-22 Iovance Biotherapeutics, Inc. Expansion of tumor infiltrating lymphocytes (tils) with adenosine a2a receptor antagonists and therapeutic combinations of tils and adenosine a2a receptor antagonists
WO2019169229A1 (en) 2018-03-01 2019-09-06 Nextcure, Inc. Klrg1 binding compositions and methods of use thereof
US10415015B2 (en) 2016-10-31 2019-09-17 Iovance Biotherapeutics, Inc. Engineered artificial antigen presenting cells for tumor infiltrating lymphocyte expansion
US10421798B2 (en) 2012-02-15 2019-09-24 Bioverativ Therapeutics Inc. Factor VIII compositions and methods of making and using same
WO2019184909A1 (en) 2018-03-27 2019-10-03 信达生物制药(苏州)有限公司 Novel antibody molecule, and preparation method and use thereof
WO2019191295A1 (en) 2018-03-28 2019-10-03 Bristol-Myers Squibb Company Interleukin-2/interleukin-2 receptor alpha fusion proteins and methods of use
WO2019222682A1 (en) 2018-05-18 2019-11-21 Bioverativ Therapeutics Inc. Methods of treating hemophilia a
WO2019229701A2 (en) 2018-06-01 2019-12-05 Novartis Ag Binding molecules against bcma and uses thereof
WO2019229658A1 (en) 2018-05-30 2019-12-05 Novartis Ag Entpd2 antibodies, combination therapies, and methods of using the antibodies and combination therapies
WO2019236417A1 (en) 2018-06-04 2019-12-12 Biogen Ma Inc. Anti-vla-4 antibodies having reduced effector function
WO2020005945A1 (en) 2018-06-26 2020-01-02 Immunogen, Inc. Immunoconjugates targeting adam9 and methods of use thereof
WO2020010117A2 (en) 2018-07-03 2020-01-09 Bristol-Myers Squibb Company Fgf21 formulations
WO2020033863A1 (en) 2018-08-09 2020-02-13 Bioverativ Therapeutics Inc. Nucleic acid molecules and uses thereof for non-viral gene therapy
US10584147B2 (en) 2013-11-08 2020-03-10 Biovertiv Therapeutics Inc. Procoagulant fusion compound
EP3620472A1 (en) 2013-08-13 2020-03-11 Sanofi Antibodies to plasminogen activator inhibitor-1 (pai-1) and uses thereof
US10597453B2 (en) 2018-06-29 2020-03-24 Gensun Biopharma, Inc. Antitumor immune checkpoint regulator antagonists
US10611794B2 (en) 2013-09-25 2020-04-07 Bioverativ Therapeutics Inc. On-column viral inactivation methods
EP3632931A1 (en) 2014-11-07 2020-04-08 Sesen Bio, Inc. Improved il-6 antibodies
WO2020070678A2 (en) 2018-10-03 2020-04-09 Staten Biotechnology B.V. Antibodies specific for human and cynomolgus apoc3 and methods of use thereof
WO2020079580A1 (en) 2018-10-15 2020-04-23 Novartis Ag Trem2 stabilizing antibodies
WO2020086665A1 (en) 2018-10-26 2020-04-30 Immunogen, Inc. Epcam antibodies, activatable antibodies, and immunoconjugates, and uses thereof
WO2020096682A2 (en) 2018-08-31 2020-05-14 Iovance Biotherapeutics, Inc. Treatment of nsclc patients refractory for anti-pd-1 antibody
WO2020096989A1 (en) 2018-11-05 2020-05-14 Iovance Biotherapeutics, Inc. Treatment of nsclc patients refractory for anti-pd-1 antibody
WO2020112781A1 (en) 2018-11-28 2020-06-04 Bristol-Myers Squibb Company Antibodies comprising modified heavy constant regions
WO2020142740A1 (en) 2019-01-04 2020-07-09 Resolve Therapeutics, Llc Treatment of sjogren's disease with nuclease fusion proteins
US10717778B2 (en) 2014-09-29 2020-07-21 Duke University Bispecific molecules comprising an HIV-1 envelope targeting arm
US10745680B2 (en) 2015-08-03 2020-08-18 Bioverativ Therapeutics Inc. Factor IX fusion proteins and methods of making and using same
WO2020176497A1 (en) 2019-02-26 2020-09-03 Rgenix, Inc. High-affinity anti-mertk antibodies and uses thereof
WO2020180733A1 (en) 2019-03-01 2020-09-10 Iovance Biotherapeutics, Inc. Expansion of tumor infiltrating lymphocytes from liquid tumors and therapeutic uses thereof
WO2020206063A1 (en) 2019-04-03 2020-10-08 Genzyme Corporation Anti-alpha beta tcr binding polypeptides with reduced fragmentation
US10836830B2 (en) 2015-12-02 2020-11-17 Agenus Inc. Antibodies and methods of use thereof
WO2020236797A1 (en) 2019-05-21 2020-11-26 Novartis Ag Variant cd58 domains and uses thereof
WO2020236792A1 (en) 2019-05-21 2020-11-26 Novartis Ag Cd19 binding molecules and uses thereof
WO2020242989A1 (en) 2019-05-24 2020-12-03 Sanofi Methods for treating systemic sclerosis
WO2020254197A1 (en) 2019-06-18 2020-12-24 Bayer Aktiengesellschaft Adrenomedullin-analogues for long-term stabilization and their use
WO2020263312A1 (en) 2019-06-28 2020-12-30 Gensun Biopharma, Inc. ANTITUMOR ANTAGONIST CONSISTING OF A MUTATED TGFβ1 - RII EXTRACELLULAR DOMAIN AND AN IMMUNOGLOBULIN SCAFFOLD
WO2021030488A1 (en) 2019-08-12 2021-02-18 Bienvenue David Leonard 4-1bb and ox40 binding proteins and related compositions and methods, antibodies against 4-1bb, antibodies against ox40
WO2021042019A1 (en) 2019-08-30 2021-03-04 Agenus Inc. Anti-cd96 antibodies and methods of use thereof
EP3789399A1 (en) 2014-11-21 2021-03-10 Bristol-Myers Squibb Company Antibodies comprising modified heavy constant regions
US10947269B2 (en) 2013-08-08 2021-03-16 Bioverativ Therapeutics Inc. Purification of chimeric FVIII molecules
WO2021053559A1 (en) 2019-09-18 2021-03-25 Novartis Ag Entpd2 antibodies, combination therapies, and methods of using the antibodies and combination therapies
WO2021053560A1 (en) 2019-09-18 2021-03-25 Novartis Ag Combination therapy with entpd2 and cd73 antibodies
WO2021062323A1 (en) 2019-09-26 2021-04-01 Stcube & Co. Antibodies specific to glycosylated ctla-4 and methods of use thereof
WO2021067389A1 (en) 2019-09-30 2021-04-08 Bioverativ Therapeutics Inc. Lentiviral vector formulations
WO2021072277A1 (en) 2019-10-09 2021-04-15 Stcube & Co. Antibodies specific to glycosylated lag3 and methods of use thereof
US10995148B2 (en) 2014-03-19 2021-05-04 Genzyme Corporation Site-specific glycoengineering of targeting moieties
US11008389B2 (en) 2011-03-16 2021-05-18 Sanofi Uses of a dual V region antibody-like protein
US11008561B2 (en) 2014-06-30 2021-05-18 Bioverativ Therapeutics Inc. Optimized factor IX gene
EP3842457A1 (en) 2015-09-09 2021-06-30 Novartis AG Thymic stromal lymphopoietin (tslp)-binding molecules and methods of using the molecules
US11072653B2 (en) 2015-06-08 2021-07-27 Macrogenics, Inc. LAG-3-binding molecules and methods of use thereof
WO2021158938A1 (en) 2020-02-06 2021-08-12 Bristol-Myers Squibb Company Il-10 and uses thereof
WO2021174034A1 (en) 2020-02-28 2021-09-02 Genzyme Corporation Modified binding polypeptides for optimized drug conjugation
WO2021216899A1 (en) * 2020-04-22 2021-10-28 Kindred Biosciences, Inc. Il4/il13 receptor molecules for veterinary use
US11168125B2 (en) 2003-05-06 2021-11-09 Bioverativ Therapeutics Inc. Immunoglobulin chimeric monomer-dimer hybrids
US11174315B2 (en) 2015-10-08 2021-11-16 Macrogenics, Inc. Combination therapy for the treatment of cancer
EP3909983A1 (en) 2015-12-02 2021-11-17 STCube & Co. Inc. Antibodies and molecules that immunospecifically bind to btn1a1 and the therapeutic uses thereof
WO2021231732A1 (en) 2020-05-15 2021-11-18 Bristol-Myers Squibb Company Antibodies to garp
WO2021233834A1 (en) 2020-05-17 2021-11-25 Astrazeneca Uk Limited Sars-cov-2 antibodies and methods of selecting and using the same
US11186638B2 (en) 2011-09-12 2021-11-30 Genzyme Corporation Anti-αβTCR antibody
WO2022006153A1 (en) 2020-06-29 2022-01-06 Resolve Therapeutics, Llc Treatment of sjogren's syndrome with nuclease fusion proteins
WO2022010798A1 (en) 2020-07-06 2022-01-13 Kiromic BioPharma, Inc. Mesothelin isoform binding molecules and chimeric pd1 receptor molecules, cells containing the same and uses thereof
US11242382B2 (en) 2020-04-20 2022-02-08 Genzyme Corporation Humanized anti-complement factor Bb antibodies
US11242402B2 (en) 2016-12-23 2022-02-08 Macrogenics, Inc. ADAM9-binding molecules, and methods of use thereof
WO2022031978A1 (en) 2020-08-06 2022-02-10 Bioverativ Usa Inc. Inflammatory cytokines and fatigue in subject with a complement mediated disease
WO2022034044A1 (en) 2020-08-10 2022-02-17 Astrazeneca Uk Limited Sars-cov-2 antibodies for treatment and prevention of covid-19
US11254748B2 (en) 2005-04-15 2022-02-22 Macrogenics, Inc. Covalent diabodies and uses thereof
US11253590B2 (en) 2015-12-02 2022-02-22 Stsciences, Inc. Antibodies specific to glycosylated BTLA (B- and T- lymphocyte attenuator)
WO2022076606A1 (en) 2020-10-06 2022-04-14 Iovance Biotherapeutics, Inc. Treatment of nsclc patients with tumor infiltrating lymphocyte therapies
WO2022076952A1 (en) 2020-10-06 2022-04-14 Iovance Biotherapeutics, Inc. Treatment of nsclc patients with tumor infiltrating lymphocyte therapies
WO2022097060A1 (en) 2020-11-06 2022-05-12 Novartis Ag Cd19 binding molecules and uses thereof
WO2022108627A1 (en) 2020-11-18 2022-05-27 Kiromic Biopharma, Inc.Kiromic Biopharma, Inc. Gamma-delta t cell manufacturing processes and chimeric pd1 receptor molecules
WO2022119976A1 (en) 2020-12-01 2022-06-09 Aptevo Research And Development Llc Heterodimeric psma and cd3-binding bispecific antibodies
US11359028B2 (en) 2016-11-09 2022-06-14 Agenus Inc. Anti-OX40 antibodies and anti-GITR antibodies
WO2022125941A1 (en) 2020-12-11 2022-06-16 Iovance Biotherapeutics, Inc. Treatment of cancer patients with tumor infiltrating lymphocyte therapies in combination with braf inhibitors and/or mek inhibitors
US11365241B2 (en) 2017-07-27 2022-06-21 Alexion Pharmaceuticals, Inc. High concentration anti-C5 antibody formulations
WO2022133149A1 (en) 2020-12-17 2022-06-23 Iovance Biotherapeutics, Inc. Treatment of cancers with tumor infiltrating lymphocytes
WO2022133140A1 (en) 2020-12-17 2022-06-23 Iovance Biotherapeutics, Inc. Treatment with tumor infiltrating lymphocyte therapies in combination with ctla-4 and pd-1 inhibitors
WO2022147196A2 (en) 2020-12-31 2022-07-07 Iovance Biotherapeutics, Inc. Devices and processes for automated production of tumor infiltrating lymphocytes
US11384149B2 (en) 2013-08-09 2022-07-12 Macrogenics, Inc. Bi-specific monovalent Fc diabodies that are capable of binding CD32B and CD79b and uses thereof
US11401348B2 (en) 2009-09-02 2022-08-02 Xencor, Inc. Heterodimeric Fc variants
WO2022165260A1 (en) 2021-01-29 2022-08-04 Iovance Biotherapeutics, Inc. Methods of making modified tumor infiltrating lymphocytes and their use in adoptive cell therapy
WO2022187741A2 (en) 2021-03-05 2022-09-09 Iovance Biotherapeutics, Inc. Tumor storage and cell culture compositions
WO2022198141A1 (en) 2021-03-19 2022-09-22 Iovance Biotherapeutics, Inc. Methods for tumor infiltrating lymphocyte (til) expansion related to cd39/cd69 selection and gene knockout in tils
WO2022204564A2 (en) 2021-03-25 2022-09-29 Iovance Biotherapeutics, Inc. Methods and compositions for t-cell coculture potency assays and use with cell therapy products
WO2022204155A1 (en) 2021-03-23 2022-09-29 Iovance Biotherapeutics, Inc. Cish gene editing of tumor infiltrating lymphocytes and uses of same in immunotherapy
US11459394B2 (en) 2017-02-24 2022-10-04 Macrogenics, Inc. Bispecific binding molecules that are capable of binding CD137 and tumor antigens, and uses thereof
WO2022212645A1 (en) 2021-03-31 2022-10-06 Bioverativ Usa Inc. Reducing surgery-associated hemolysis in cold agglutinin disease patients
WO2022225981A2 (en) 2021-04-19 2022-10-27 Iovance Biotherapeutics, Inc. Chimeric costimulatory receptors, chemokine receptors, and the use of same in cellular immunotherapies
WO2022245754A1 (en) 2021-05-17 2022-11-24 Iovance Biotherapeutics, Inc. Pd-1 gene-edited tumor infiltrating lymphocytes and uses of same in immunotherapy
WO2022256820A1 (en) 2021-06-03 2022-12-08 Gensun Biopharma Inc. Multispecific antagonists
WO2022263357A1 (en) 2021-06-14 2022-12-22 Argenx Iip Bv Anti-il-9 antibodies and methods of use thereof
WO2023004074A2 (en) 2021-07-22 2023-01-26 Iovance Biotherapeutics, Inc. Method for cryopreservation of solid tumor fragments
WO2023010060A2 (en) 2021-07-27 2023-02-02 Novab, Inc. Engineered vlrb antibodies with immune effector functions
WO2023009716A1 (en) 2021-07-28 2023-02-02 Iovance Biotherapeutics, Inc. Treatment of cancer patients with tumor infiltrating lymphocyte therapies in combination with kras inhibitors
WO2023031615A1 (en) 2021-09-02 2023-03-09 Djs Antibodies Ltd Polypeptides
WO2023039488A1 (en) 2021-09-09 2023-03-16 Iovance Biotherapeutics, Inc. Processes for generating til products using pd-1 talen knockdown
WO2023049862A1 (en) 2021-09-24 2023-03-30 Iovance Biotherapeutics, Inc. Expansion processes and agents for tumor infiltrating lymphocytes
WO2023056362A1 (en) 2021-09-30 2023-04-06 Seagen Inc. B7-h4 antibody-drug conjugates for the treatment of cancer
WO2023077015A2 (en) 2021-10-27 2023-05-04 Iovance Biotherapeutics, Inc. Systems and methods for coordinating manufacturing of cells for patient-specific immunotherapy
US11642398B2 (en) 2013-03-15 2023-05-09 Bioverativ Therapeutics Inc. Factor IX polypeptide formulations
WO2023079086A1 (en) 2021-11-05 2023-05-11 Astrazeneca Uk Limited Composition for treatment and prevention of covid-19
WO2023086803A1 (en) 2021-11-10 2023-05-19 Iovance Biotherapeutics, Inc. Methods of expansion treatment utilizing cd8 tumor infiltrating lymphocytes
WO2023091968A1 (en) 2021-11-17 2023-05-25 Disc Medicine, Inc. Methods for treating anemia of kidney disease
US11685781B2 (en) 2018-02-15 2023-06-27 Macrogenics, Inc. Variant CD3-binding domains and their use in combination therapies for the treatment of disease
WO2023147488A1 (en) 2022-01-28 2023-08-03 Iovance Biotherapeutics, Inc. Cytokine associated tumor infiltrating lymphocytes compositions and methods
WO2023147486A1 (en) 2022-01-28 2023-08-03 Iovance Biotherapeutics, Inc. Tumor infiltrating lymphocytes engineered to express payloads
EP4223783A2 (en) 2012-09-12 2023-08-09 Genzyme Corporation Fc containing polypeptides with altered glycosylation and reduced effector function
US11746148B2 (en) 2018-03-27 2023-09-05 Innovent Biologics (Suzhou) Co., Ltd. Antibody molecules comprising a single-domain antigen-binding site and Fab fragments
EP4249066A2 (en) 2014-12-23 2023-09-27 Bristol-Myers Squibb Company Antibodies to tigit
US11773160B1 (en) 2022-08-05 2023-10-03 Anaveon AG Immune-stimulating IL-2 fusion proteins
WO2023196877A1 (en) 2022-04-06 2023-10-12 Iovance Biotherapeutics, Inc. Treatment of nsclc patients with tumor infiltrating lymphocyte therapies
WO2023201369A1 (en) 2022-04-15 2023-10-19 Iovance Biotherapeutics, Inc. Til expansion processes using specific cytokine combinations and/or akti treatment
US11795226B2 (en) 2017-12-12 2023-10-24 Macrogenics, Inc. Bispecific CD16-binding molecules and their use in the treatment of disease
WO2023209568A1 (en) 2022-04-26 2023-11-02 Novartis Ag Multispecific antibodies targeting il-13 and il-18
WO2023209177A1 (en) 2022-04-29 2023-11-02 Astrazeneca Uk Limited Sars-cov-2 antibodies and methods of using the same
WO2023220608A1 (en) 2022-05-10 2023-11-16 Iovance Biotherapeutics, Inc. Treatment of cancer patients with tumor infiltrating lymphocyte therapies in combination with an il-15r agonist
US11820830B2 (en) 2004-07-20 2023-11-21 Xencor, Inc. Optimized Fc variants
WO2023240124A1 (en) 2022-06-07 2023-12-14 Regeneron Pharmaceuticals, Inc. Pseudotyped viral particles for targeting tcr-expressing cells
WO2023240109A1 (en) 2022-06-07 2023-12-14 Regeneron Pharmaceuticals, Inc. Multispecific molecules for modulating t-cell activity, and uses thereof
WO2023242362A1 (en) 2022-06-15 2023-12-21 argenx BV Fcrn/antigen-binding molecules and methods of use
WO2023245048A1 (en) 2022-06-15 2023-12-21 Bioverativ Usa Inc. Anti-complement c1s antibody formulation
US11851482B2 (en) 2016-04-04 2023-12-26 Genzyme Corporation Anti-complement factor Bb antibodies and uses thereof
WO2023250507A1 (en) 2022-06-24 2023-12-28 Bioverativ Usa Inc. Methods for treating complement-mediated diseases
WO2024011114A1 (en) 2022-07-06 2024-01-11 Iovance Biotherapeutics, Inc. Devices and processes for automated production of tumor infiltrating lymphocytes
WO2024015830A1 (en) 2022-07-12 2024-01-18 Cytomx Therapeutics, Inc. Epcam immunoconjugates and uses thereof
WO2024026474A1 (en) 2022-07-29 2024-02-01 Regeneron Pharmaceuticals, Inc. Compositions and methods for transferrin receptor (tfr)-mediated delivery to the brain and muscle
WO2024026494A1 (en) 2022-07-29 2024-02-01 Regeneron Pharmaceuticals, Inc. Viral particles retargeted to transferrin receptor 1
WO2024026470A2 (en) 2022-07-29 2024-02-01 Regeneron Pharmaceuticals, Inc. Anti-tfr:payload fusions and methods of use thereof
WO2024030758A1 (en) 2022-08-01 2024-02-08 Iovance Biotherapeutics, Inc. Chimeric costimulatory receptors, chemokine receptors, and the use of same in cellular immunotherapies
WO2024050524A1 (en) 2022-09-01 2024-03-07 University Of Georgia Research Foundation, Inc. Compositions and methods for directing apolipoprotein l1 to induce mammalian cell death
US11932685B2 (en) 2020-10-23 2024-03-19 Xencor, Inc. Fc variants with altered binding to FcRn

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5623053A (en) * 1992-01-10 1997-04-22 California Institute Of Technology Soluble mammal-derived Fc receptor which binds at a pH ranging from about 5.5 to 6.5 and releases at a pH ranging from about 7.5 to 8.5

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5623053A (en) * 1992-01-10 1997-04-22 California Institute Of Technology Soluble mammal-derived Fc receptor which binds at a pH ranging from about 5.5 to 6.5 and releases at a pH ranging from about 7.5 to 8.5

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
BIOCHEMISTRY, 1995, Vol. 34, RAGHAVAN M. et al., "Analysis of the pH Dependence of the Neonatal Fc Receptor/Immunoglobulin G Interaction Using Antibody and Receptor Variants", pages 14649-14657. *
J. EXP. MED., December 1994, Vol. 180, STORY C.M. et al., "A Major Histocompatibility Complex Class I-Like Fc Receptor Cloned from Human Placenta: Possible Role in Transfer of Immunoglobulin G from Mother to Fetus", pages 2377-2381. *
NATURE, 12 January 1989, Vol. 337, SIMISTER N.E. et al., "An Fc Receptor Structurally-Related to MHC Class I Antigens", pages 184-187. *

Cited By (689)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999051642A1 (en) * 1998-04-02 1999-10-14 Genentech, Inc. Antibody variants and fragments thereof
US7741072B2 (en) 1998-04-02 2010-06-22 Genentech, Inc. Polypeptide variants
US7297775B2 (en) 1998-04-02 2007-11-20 Genentech, Inc. Polypeptide variants
US6194551B1 (en) 1998-04-02 2001-02-27 Genentech, Inc. Polypeptide variants
US6242195B1 (en) 1998-04-02 2001-06-05 Genentech, Inc. Methods for determining binding of an analyte to a receptor
US7364731B2 (en) 1998-04-02 2008-04-29 Genentech, Inc. Polypeptide variants
US6528624B1 (en) 1998-04-02 2003-03-04 Genentech, Inc. Polypeptide variants
US6538124B1 (en) 1998-04-02 2003-03-25 Genentech, Inc. Polypeptide variants
JP2003512019A (en) * 1999-01-15 2003-04-02 ジェネンテック・インコーポレーテッド Polypeptide variants with altered effector functions
KR100887482B1 (en) * 1999-01-15 2009-03-10 제넨테크, 인크. Polypeptide Variants with Altered Effector Function
US6737056B1 (en) 1999-01-15 2004-05-18 Genentech, Inc. Polypeptide variants with altered effector function
US7785791B2 (en) 1999-01-15 2010-08-31 Genentech, Inc. Polypeptide variants with altered effector function
CN1763097B (en) * 1999-01-15 2011-04-13 杰南技术公司 Polypeptide variants with altered effector function
EP2366713A3 (en) * 1999-01-15 2012-06-27 Genentech, Inc. Polypeptide variants with altered effector function
WO2000042072A3 (en) * 1999-01-15 2000-11-30 Genentech Inc Polypeptide variants with altered effector function
JP2010227116A (en) * 1999-01-15 2010-10-14 Genentech Inc Polypeptide variant with altered effector function
WO2000042072A2 (en) 1999-01-15 2000-07-20 Genentech, Inc. Polypeptide variants with altered effector function
US7183387B1 (en) 1999-01-15 2007-02-27 Genentech, Inc. Polypeptide variants with altered effector function
EP2386574A3 (en) * 1999-01-15 2012-06-27 Genentech, Inc. Polypeptide variants with altered effector function
US7790858B2 (en) 1999-01-15 2010-09-07 Genentech, Inc. Polypeptide variants with altered effector function
JP2013166770A (en) * 1999-01-15 2013-08-29 Genentech Inc Polypeptide variants with altered effector function
US7371826B2 (en) 1999-01-15 2008-05-13 Genentech, Inc. Polypeptide variants with altered effector function
EP2364997A3 (en) * 1999-01-15 2012-07-04 Genentech, Inc. Polypeptide variants with altered effector function
US8163882B2 (en) 1999-01-15 2012-04-24 Genentech, Inc. Polypeptide variants with altered effector function
US7122637B2 (en) 1999-01-15 2006-10-17 Genentech, Inc. Polypeptide variants with altered effector function
US7416727B2 (en) 1999-01-15 2008-08-26 Genentech, Inc. Polypeptide variants with altered effector function
US7332581B2 (en) 1999-01-15 2008-02-19 Genentech, Inc. Polypeptide variants with altered effector function
US7335742B2 (en) 1999-01-15 2008-02-26 Genentech, Inc. Polypeptide variants with altered effector function
AU2008229968B2 (en) * 1999-01-15 2012-08-09 Genentech, Inc. Polypeptide variants with altered effector function
EP2264072A1 (en) 2000-04-13 2010-12-22 The Rockefeller University Enhancement of antibody-mediated cytotoxicity.
US7416726B2 (en) 2000-04-13 2008-08-26 The Rockefeller University Enhancement of antibody-mediated immune responses
AU2008201419A1 (en) * 2000-12-12 2008-04-24 Board Of Regents, The University Of Texas System Molecules with extended half-lives, compositions and uses thereof
AU2011253690C1 (en) * 2000-12-12 2018-01-18 Board Of Regents, The University Of Texas System Molecules with extended half-lives, compositions and uses thereof
US8323962B2 (en) 2000-12-12 2012-12-04 Medimmune, Llc Molecules with extended half-lives, compositions and uses thereof
AU2011253690B2 (en) * 2000-12-12 2013-11-07 Board Of Regents, The University Of Texas System Molecules with extended half-lives, compositions and uses thereof
AU2002248184B2 (en) * 2000-12-12 2008-01-10 Board Of Regents, The University Of Texas System Molecules with extended half-lives, compositions and uses thereof
AU2014200579B2 (en) * 2000-12-12 2016-01-21 Board Of Regents, The University Of Texas System Molecules with extended half-lives, compositions and uses thereof
AU2014200579A1 (en) * 2000-12-12 2014-02-20 Board Of Regents, The University Of Texas System Molecules with extended half-lives, compositions and uses thereof
EP3569610A2 (en) 2000-12-12 2019-11-20 Medlmmune, LLC Molecules with extended half lives, compositions and uses thereof
US8475792B2 (en) 2000-12-12 2013-07-02 Medimmune, Llc Molecules with extended half-lives, compositions and uses thereof
JP2014050385A (en) * 2000-12-12 2014-03-20 Medimmune Llc Molecule having extended half-life, and composition and use thereof
JP2016020344A (en) * 2000-12-12 2016-02-04 メディミューン,エルエルシー Molecules with extended half-lives, compositions and uses thereof
US7658921B2 (en) 2000-12-12 2010-02-09 Medimmune, Llc Molecules with extended half-lives, compositions and uses thereof
AU2002248184C1 (en) * 2000-12-12 2018-01-04 Board Of Regents, The University Of Texas System Molecules with extended half-lives, compositions and uses thereof
AU2008201419C1 (en) * 2000-12-12 2018-01-18 Board Of Regents, The University Of Texas System Molecules with extended half-lives, compositions and uses thereof
US7670600B2 (en) 2000-12-12 2010-03-02 MedImmine, LLC Molecules with extended half-lives, compositions and uses thereof
AU2016202471C1 (en) * 2000-12-12 2017-11-09 Board Of Regents, The University Of Texas System Molecules with extended half-lives, compositions and uses thereof
US8795661B2 (en) 2000-12-12 2014-08-05 Medimmune, Llc Molecules with extended half-lives, compositions and uses thereof
US7704497B2 (en) 2000-12-12 2010-04-27 Medimmune, Llc Molecules with extended half-lives, compositions and uses thereof
AU2011253690A1 (en) * 2000-12-12 2011-12-22 Board Of Regents, The University Of Texas System Molecules with extended half-lives, compositions and uses thereof
US8012476B2 (en) 2000-12-12 2011-09-06 Medimmune, Llc Molecules with extended half-lives, compositions and uses thereof
AU2008201419B2 (en) * 2000-12-12 2011-09-01 Board Of Regents, The University Of Texas System Molecules with extended half-lives, compositions and uses thereof
US7083784B2 (en) 2000-12-12 2006-08-01 Medimmune, Inc. Molecules with extended half-lives, compositions and uses thereof
AU2016202471B2 (en) * 2000-12-12 2017-05-25 Board Of Regents, The University Of Texas System Molecules with extended half-lives, compositions and uses thereof
EP2357187A1 (en) 2000-12-12 2011-08-17 MedImmune, LLC Molecules with extended half-lives, compositions and uses thereof
EP2354149A1 (en) 2000-12-12 2011-08-10 MedImmune, LLC Molecules with extended half-lives, compositions and uses thereof
EP2341060A1 (en) 2000-12-12 2011-07-06 MedImmune, LLC Molecules with extended half-lives, compositions and uses thereof
JP2010154855A (en) * 2000-12-12 2010-07-15 Medimmune Llc Molecule with extended half-life, and composition and use thereof
US9562100B2 (en) 2000-12-12 2017-02-07 Medimmune Llc Molecules with extended half-lives, compositions and uses thereof
AU2014200579C1 (en) * 2000-12-12 2018-01-18 Board Of Regents, The University Of Texas System Molecules with extended half-lives, compositions and uses thereof
EP1355919A4 (en) * 2000-12-12 2005-02-09 Medimmune Inc Molecules with extended half-lives, compositions and uses thereof
EP1355919A2 (en) * 2000-12-12 2003-10-29 Medimmune, Inc. Molecules with extended half-lives, compositions and uses thereof
WO2002060919A2 (en) 2000-12-12 2002-08-08 Medimmune, Inc. Molecules with extended half-lives, compositions and uses thereof
US8124731B2 (en) 2002-03-01 2012-02-28 Xencor, Inc. Optimized Fc variants and methods for their generation
US8734791B2 (en) 2002-03-01 2014-05-27 Xencor, Inc. Optimized fc variants and methods for their generation
US7662925B2 (en) 2002-03-01 2010-02-16 Xencor, Inc. Optimized Fc variants and methods for their generation
US8093357B2 (en) 2002-03-01 2012-01-10 Xencor, Inc. Optimized Fc variants and methods for their generation
US9272032B2 (en) 2002-06-14 2016-03-01 Medimmune, Llc Stabilized liquid anti-RSV antibody formulations
US10604560B2 (en) 2002-06-14 2020-03-31 Arexis Ab Stabilized liquid anti-RSV antibody formulations
US7132100B2 (en) 2002-06-14 2006-11-07 Medimmune, Inc. Stabilized liquid anti-RSV antibody formulations
US9879067B2 (en) 2002-06-14 2018-01-30 Medimmune, Llc Stabilized liquid anti-RSV antibody formulations
US7425618B2 (en) 2002-06-14 2008-09-16 Medimmune, Inc. Stabilized anti-respiratory syncytial virus (RSV) antibody formulations
EP2206516A1 (en) 2002-06-14 2010-07-14 Medimmune, LLC Stabilized liquid anti-RSV antibody formulations
US11180542B2 (en) 2002-06-14 2021-11-23 Arexis Ab Stabilized liquid anti-RSV antibody formulations
US8986686B2 (en) 2002-06-14 2015-03-24 Medimmune, Llc Stabilized liquid anti-RSV antibody formulations
EP2570432A1 (en) 2002-06-14 2013-03-20 Medimmune, Inc. Stabilized anti-respiratory syncytial virus (RSV) antibody formulations
US7294336B2 (en) 2002-06-14 2007-11-13 Medimmune, Inc. Stabilized liquid anti-RSV antibody formulations
EP2327421A1 (en) 2002-06-14 2011-06-01 MedImmune, LLC Stabilized liquid anti-RSV antibody formulations
EP2371389A2 (en) 2002-08-14 2011-10-05 MacroGenics, Inc. FcgammaRIIB-specific antibodies and methods of use thereof
US8530627B2 (en) 2002-08-14 2013-09-10 Macrogenics, Inc. FcγRIIB specific antibodies and methods of use thereof
US8968730B2 (en) 2002-08-14 2015-03-03 Macrogenics Inc. FcγRIIB specific antibodies and methods of use thereof
US8946387B2 (en) 2002-08-14 2015-02-03 Macrogenics, Inc. FcγRIIB specific antibodies and methods of use thereof
US8187593B2 (en) 2002-08-14 2012-05-29 Macrogenics, Inc. FcγRIIB specific antibodies and methods of use thereof
US10184000B2 (en) 2002-09-27 2019-01-22 Xencor, Inc. Optimized Fc variants and methods for their generation
US8093359B2 (en) 2002-09-27 2012-01-10 Xencor, Inc. Optimized Fc variants and methods for their generation
US8188231B2 (en) 2002-09-27 2012-05-29 Xencor, Inc. Optimized FC variants
US10183999B2 (en) 2002-09-27 2019-01-22 Xencor, Inc. Optimized Fc variants and methods for their generation
US8039592B2 (en) 2002-09-27 2011-10-18 Xencor, Inc. Optimized Fc variants and methods for their generation
US8383109B2 (en) 2002-09-27 2013-02-26 Xencor, Inc. Optimized Fc variants and methods for their generation
US8809503B2 (en) 2002-09-27 2014-08-19 Xencor, Inc. Optimized Fc variants and methods for their generation
US8858937B2 (en) 2002-09-27 2014-10-14 Xencor, Inc. Optimized Fc variants and methods for their generation
US9353187B2 (en) 2002-09-27 2016-05-31 Xencor, Inc. Optimized FC variants and methods for their generation
US9193798B2 (en) 2002-09-27 2015-11-24 Xencor, Inc. Optimized Fc variants and methods for their generation
US7217797B2 (en) 2002-10-15 2007-05-15 Pdl Biopharma, Inc. Alteration of FcRn binding affinities or serum half-lives of antibodies by mutagenesis
US7365168B2 (en) 2002-10-15 2008-04-29 Pdl Biopharma, Inc. Alteration of FcRn binding affinities or serum half-lives of antibodies by mutagenesis
US8624007B2 (en) 2002-10-15 2014-01-07 Abbvie Biotherapeutics Inc. Alteration of Fc-fusion protein serum half-lives by mutagenesis
US7732570B2 (en) 2002-10-15 2010-06-08 Facet Biotech Corporation Alteration of Fc-fusion protein serum half-lives by mutagenesis
EP3301114A1 (en) 2002-10-16 2018-04-04 Purdue Pharma LP Fusion polypeptides of antibodies that bind cell-associated ca 125/o722p
EP2298806A1 (en) 2002-10-16 2011-03-23 Purdue Pharma L.P. Antibodies that bind cell-associated CA 125/0722P and methods of use thereof
EP2891666A1 (en) 2002-10-16 2015-07-08 Purdue Pharma L.P. Antibodies that bind cell-associated CA 125/O722P and methods of use thereof
US9028815B2 (en) 2003-01-09 2015-05-12 Macrogenics, Inc. Identification and engineering of antibodies with variant FC regions and methods of using same
US7355008B2 (en) 2003-01-09 2008-04-08 Macrogenics, Inc. Identification and engineering of antibodies with variant Fc regions and methods of using same
US8951517B2 (en) 2003-01-09 2015-02-10 Macrogenics, Inc. Identification and engineering of antibodies with variant Fc regions and methods of using same
US8735545B2 (en) 2003-03-03 2014-05-27 Xencor, Inc. Fc variants having increased affinity for fcyrllc
US8937158B2 (en) 2003-03-03 2015-01-20 Xencor, Inc. Fc variants with increased affinity for FcγRIIc
US10113001B2 (en) 2003-03-03 2018-10-30 Xencor, Inc. Fc variants with increased affinity for FcyRIIc
US9663582B2 (en) 2003-03-03 2017-05-30 Xencor, Inc. Optimized Fc variants
US8388955B2 (en) 2003-03-03 2013-03-05 Xencor, Inc. Fc variants
US8084582B2 (en) 2003-03-03 2011-12-27 Xencor, Inc. Optimized anti-CD20 monoclonal antibodies having Fc variants
US10584176B2 (en) 2003-03-03 2020-03-10 Xencor, Inc. Fc variants with increased affinity for FcγRIIc
US9657106B2 (en) 2003-03-03 2017-05-23 Xencor, Inc. Optimized Fc variants
EP2316487A1 (en) 2003-04-11 2011-05-04 MedImmune, LLC Recombinant IL-9 antibodies & uses thereof
US9051373B2 (en) 2003-05-02 2015-06-09 Xencor, Inc. Optimized Fc variants
US11168125B2 (en) 2003-05-06 2021-11-09 Bioverativ Therapeutics Inc. Immunoglobulin chimeric monomer-dimer hybrids
US8603473B2 (en) 2003-06-27 2013-12-10 Biogen Idec Ma Inc. Modified binding molecules comprising connecting peptides
US7700097B2 (en) 2003-06-27 2010-04-20 Biogen Idec Ma Inc. Purification and preferential synthesis of binding molecules
EP2292264A2 (en) 2003-07-24 2011-03-09 Innate Pharma Methods and compositions for increasing the efficiency of therapeutic antibodies using NK cell potentiating compounds
US8318917B2 (en) 2003-08-22 2012-11-27 Biogen Idec Ma Inc. Nucleic acids encoding antibodies having altered effector function and methods for making the same
US7863419B2 (en) 2003-08-22 2011-01-04 Biogen Idec Ma Inc. Antibodies having altered effector function and methods for making the same
US9714282B2 (en) 2003-09-26 2017-07-25 Xencor, Inc. Optimized Fc variants and methods for their generation
JP2007531707A (en) * 2003-10-15 2007-11-08 ピーディーエル バイオファーマ, インコーポレイテッド Modification of Fc fusion protein serum half-life by mutagenesis of heavy chain constant region positions 250, 314 and / or 428 of IG
US7217798B2 (en) 2003-10-15 2007-05-15 Pdl Biopharma, Inc. Alteration of Fc-fusion protein serum half-lives by mutagenesis
WO2005037867A1 (en) * 2003-10-15 2005-04-28 Pdl Biopharma, Inc. ALTERATION OF Fc-FUSION PROTEIN SERUM HALF-LIVES BY MUTAGENESIS OF POSITIONS 250, 314 AND/OR 428 OF THE HEAVY CHAIN CONSTANT REGION OF IG
US8618252B2 (en) 2003-11-12 2013-12-31 Biogen Idec Ma Inc. Neonatal Fc receptor (FcRn)-binding polypeptide variants, dimeric Fc binding proteins and methods related thereto
US7371381B2 (en) 2003-12-12 2008-05-13 Amgen Inc. Anti-galanin antibodies and uses thereof
US7919086B2 (en) 2004-07-09 2011-04-05 Chugai Seiyaku Kabushiki Kaisha Anti-glypican 3 antibody
US11820830B2 (en) 2004-07-20 2023-11-21 Xencor, Inc. Optimized Fc variants
US8647625B2 (en) 2004-07-26 2014-02-11 Biogen Idec Ma Inc. Anti-CD154 antibodies
US8961976B2 (en) 2004-07-26 2015-02-24 Biogen Idec Ma Inc. Anti-CD154 antibodies
US7740847B2 (en) 2004-08-04 2010-06-22 Applied Molecular Evolution, Inc. Variant Fc regions
US7659374B2 (en) 2004-08-16 2010-02-09 Medimmune, Llc Eph receptor Fc variants with enhanced antibody dependent cell-mediated cytotoxicity activity
US7871613B2 (en) 2004-08-24 2011-01-18 Chugai Seiyaku Kabushiki Kaisha Adjuvant therapy with the use of anti-glypican 3 antibody
EP3073267A1 (en) 2004-09-21 2016-09-28 Medimmune, Inc. Antibodies against and methods for producing vaccines for respiratory syncytial virus
US8101720B2 (en) 2004-10-21 2012-01-24 Xencor, Inc. Immunoglobulin insertions, deletions and substitutions
US7867734B2 (en) 2004-10-26 2011-01-11 Chugai Seiyaku Kabushiki Kaisha Anti-glypican 3 antibody having modified sugar chain
US7632497B2 (en) 2004-11-10 2009-12-15 Macrogenics, Inc. Engineering Fc Antibody regions to confer effector function
US8367805B2 (en) 2004-11-12 2013-02-05 Xencor, Inc. Fc variants with altered binding to FcRn
EP2332985A3 (en) * 2004-11-12 2012-01-25 Xencor, Inc. Fc variants with altered binding to FcRn
US8802820B2 (en) 2004-11-12 2014-08-12 Xencor, Inc. Fc variants with altered binding to FcRn
US8852586B2 (en) 2004-11-12 2014-10-07 Xencor, Inc. Fc variants with altered binding to FcRn
JP2008519860A (en) * 2004-11-12 2008-06-12 ゼンコー・インコーポレイテッド Fc variants with altered binding to FcRn
EP2325206A3 (en) * 2004-11-12 2011-10-19 Xencor, Inc. FC variants with altered binding to FCRN
US8883973B2 (en) 2004-11-12 2014-11-11 Xencor, Inc. Fc variants with altered binding to FcRn
US9200079B2 (en) 2004-11-12 2015-12-01 Xencor, Inc. Fc variants with altered binding to FcRn
US11198739B2 (en) 2004-11-12 2021-12-14 Xencor, Inc. Fc variants with altered binding to FcRn
EP2314618A3 (en) * 2004-11-12 2011-10-19 Xencor Inc. Fc variants with altered binding to FcRn
EP2325207A3 (en) * 2004-11-12 2011-10-19 Xencor, Inc. FC variants with altered binding to FCRN
WO2006053301A3 (en) * 2004-11-12 2007-04-05 Xencor Inc Fc variants with altered binding to fcrn
US10336818B2 (en) 2004-11-12 2019-07-02 Xencor, Inc. Fc variants with altered binding to FcRn
US8394925B2 (en) 2004-11-12 2013-03-12 Xencor, Inc. Fc variants with altered binding to FcRn
AU2011200066B2 (en) * 2004-11-12 2012-07-26 Xencor, Inc. Fc variants with altered binding to FcRn
US9803023B2 (en) 2004-11-12 2017-10-31 Xencor, Inc. Fc variants with altered binding to FcRn
JP4652414B2 (en) * 2004-11-12 2011-03-16 ゼンコー・インコーポレイテッド Fc variants with altered binding to FcRn
US8318907B2 (en) 2004-11-12 2012-11-27 Xencor, Inc. Fc variants with altered binding to FcRn
EP2845865A1 (en) * 2004-11-12 2015-03-11 Xencor Inc. Fc variants with altered binding to FcRn
US8324351B2 (en) 2004-11-12 2012-12-04 Xencor, Inc. Fc variants with altered binding to FcRn
US8546543B2 (en) 2004-11-12 2013-10-01 Xencor, Inc. Fc variants that extend antibody half-life
US8338574B2 (en) 2004-11-12 2012-12-25 Xencor, Inc. FC variants with altered binding to FCRN
WO2006089133A2 (en) 2005-02-15 2006-08-24 Duke University Anti-cd19 antibodies and uses in oncology
US11254748B2 (en) 2005-04-15 2022-02-22 Macrogenics, Inc. Covalent diabodies and uses thereof
US9296816B2 (en) 2005-04-15 2016-03-29 Macrogenics, Inc. Covalent diabodies and uses thereof
US10093738B2 (en) 2005-04-15 2018-10-09 Macrogenics, Inc. Covalent diabodies and uses thereof
US9889197B2 (en) 2005-04-15 2018-02-13 Macrogenics, Inc. Covalently-associated diabody complexes that possess charged coil domains and that are capable of enhanced binding to serum albumin
US9284375B2 (en) 2005-04-15 2016-03-15 Macrogenics, Inc. Covalent diabodies and uses thereof
US10093739B2 (en) 2005-04-15 2018-10-09 Macrogenics, Inc. Covalent diabodies and uses thereof
US11254747B2 (en) 2005-04-15 2022-02-22 Macrogenics, Inc. Covalent diabodies and uses thereof
US9963510B2 (en) 2005-04-15 2018-05-08 Macrogenics, Inc. Covalent diabodies and uses thereof
US8008443B2 (en) 2005-04-26 2011-08-30 Medimmune, Llc Modulation of antibody effector function by hinge domain engineering
US8697396B2 (en) 2005-04-26 2014-04-15 Medimmune, Llc Modulation of antibody effector function by hinge domain engineering
EP2221316A1 (en) 2005-05-05 2010-08-25 Duke University Anti-CD19 antibody therapy for autoimmune disease
US8309690B2 (en) 2005-07-01 2012-11-13 Medimmune, Llc Integrated approach for generating multidomain protein therapeutics
US8697071B2 (en) 2005-08-10 2014-04-15 Macrogenics, Inc. Identification and engineering of antibodies with variant Fc regions and methods of using same
EP2573114A1 (en) 2005-08-10 2013-03-27 MacroGenics, Inc. Identification and engineering of antibodies with variant Fc regions and methods of using same
US9040041B2 (en) 2005-10-03 2015-05-26 Xencor, Inc. Modified FC molecules
US7973136B2 (en) 2005-10-06 2011-07-05 Xencor, Inc. Optimized anti-CD30 antibodies
US9574006B2 (en) 2005-10-06 2017-02-21 Xencor, Inc. Optimized anti-CD30 antibodies
US10118959B2 (en) 2005-10-14 2018-11-06 Chugai Seiyaku Kabushiki Kaisha Anti-glypican-3 antibody
US9102739B2 (en) 2005-10-14 2015-08-11 Chugai Seiyaku Kabushiki Kaisha Anti-glypican-3 antibody
US9567389B2 (en) 2005-10-14 2017-02-14 Medimmune, Llc Cell display of antibody libraries
US8409568B2 (en) 2005-10-14 2013-04-02 Medimmune, Llc Mutant antibody Fc domains and fusion proteins thereof
US9012603B2 (en) 2006-02-17 2015-04-21 Biogen Idec Hemophilia Inc. Peptides that block the binding of IgG to FcRn
EP2540741A1 (en) 2006-03-06 2013-01-02 Aeres Biomedical Limited Humanized anti-CD22 antibodies and their use in treatment of oncology, transplantation and autoimmune disease
US7786270B2 (en) 2006-05-26 2010-08-31 Macrogenics, Inc. Humanized FcγRIIB-specific antibodies and methods of use thereof
WO2007147090A2 (en) 2006-06-14 2007-12-21 Macrogenics, Inc. Methods for the treatment of autoimmune disorders using monoclonal antibodies with reduced toxicity
EP2815764A1 (en) 2006-06-14 2014-12-24 Macrogenics, Inc. Methods for the treatment of autoimmune disorders using monoclonal antibodies with reduced toxicity
US9737599B2 (en) 2006-06-26 2017-08-22 Macrogenics, Inc. Combination of FcγRIIB-specific antibodies and CD20-specific antibodies and methods of use thereof
US11098125B2 (en) 2006-06-26 2021-08-24 Macrogenics, Inc. FcγRIIB-specific antibodies and methods of use thereof
US10100116B2 (en) 2006-06-26 2018-10-16 Macrogenics, Inc. FcγRIIB-specific antibodies and methods of use thereof
EP2505209A1 (en) 2006-06-26 2012-10-03 MacroGenics, Inc. Fcgamma-RIIB-specific antibodies and methods of the use thereof
US10626182B2 (en) 2006-08-14 2020-04-21 Xencor, Inc. Optimized antibodies that target CD19
US11618788B2 (en) 2006-08-14 2023-04-04 Xencor, Inc. Optimized antibodies that target CD19
US8524867B2 (en) 2006-08-14 2013-09-03 Xencor, Inc. Optimized antibodies that target CD19
US9803020B2 (en) 2006-08-14 2017-10-31 Xencor, Inc. Optimized antibodies that target CD19
US8394374B2 (en) 2006-09-18 2013-03-12 Xencor, Inc. Optimized antibodies that target HM1.24
US9040042B2 (en) 2006-09-18 2015-05-26 Xencor, Inc. Optimized antibodies that target HM1.24
US9708408B2 (en) 2006-12-08 2017-07-18 Macrogenics, Inc. Methods for the treatment of disease using immunoglobulins having Fc Regions with altered affinities for FcγRactivating and FcγRinhibiting
US11787871B2 (en) 2006-12-08 2023-10-17 Macrogenics, Inc. Methods for the treatment of disease using immunoglobulins having fc regions with altered affinities for FcgammaRactivating and FegammaRinhibiting
US10711069B2 (en) 2006-12-08 2020-07-14 Macrogenics, Inc. Methods for the treatment of disease using immunoglobulins having Fc regions with altered affinities for FcγRactivating and FcγRinhibiting
WO2008136694A1 (en) 2007-05-04 2008-11-13 Technophage, Investigação E Desenvolvimento Em Biotecnologia, Sa Engineered rabbit antibody variable domains and uses thereof
EP2737907A2 (en) 2007-05-07 2014-06-04 MedImmune, LLC Anti-icos antibodies and their use in treatment of oncology, transplantation and autoimmune disease
EP2703011A2 (en) 2007-05-07 2014-03-05 MedImmune, LLC Anti-icos antibodies and their use in treatment of oncology, transplantation and autoimmune disease
EP3072525A1 (en) 2007-05-14 2016-09-28 MedImmune, LLC Methods of reducing basophil levels
US9321831B2 (en) 2007-06-01 2016-04-26 Medimmune Limited RSV-specific binding molecules and means for producing them
US10730931B2 (en) 2007-06-01 2020-08-04 Medimmune Limited RSV-specific binding molecules and means for producing them
US10059757B2 (en) 2007-06-01 2018-08-28 Medimmune Limited RSV-specific binding molecules and means for producing them
US8906844B2 (en) 2007-08-09 2014-12-09 Biogen Idec Hemophilia Inc. Immunomodulatory peptides
US9228019B2 (en) 2007-08-29 2016-01-05 Sanofi Humanized anti-CXCR5 antibodies, derivatives thereof and their use
US8647622B2 (en) 2007-08-29 2014-02-11 Sanofi Humanized anti-CXCR5 antibodies, derivatives thereof and their use
US9815902B2 (en) 2007-08-29 2017-11-14 Sanofi Humanized anti-CXCR5 antibodies, derivatives thereof and their uses
US8980262B2 (en) 2007-08-29 2015-03-17 Sanofi Humanized anti-CXCR5 antibodies, derivatives thereof and their use
US9243067B2 (en) 2007-08-29 2016-01-26 Sanofi Humanized anti-CXCR5 antibodies, derivatives thereof and their use
US9175087B2 (en) 2007-08-29 2015-11-03 Sanofi Humanized anti-CXCR5 antibodies, derivatives thereof and their use
EP2573121A1 (en) 2007-10-15 2013-03-27 Sanofi Antibodies that bind il-4 and/or il-13 and their uses
US11453727B2 (en) 2007-10-15 2022-09-27 Sanofi Antibodies that bind IL-4 and/or IL-13 and their uses
US8388965B2 (en) 2007-10-15 2013-03-05 Sanofi Antibodies that bind IL-4 and/or IL-13 and their uses
EP3686220A1 (en) 2007-10-15 2020-07-29 Sanofi Antibodies that bind il-4 and/or il-13 and their uses
US10759871B2 (en) 2007-10-15 2020-09-01 Sanofi Antibodies that bind IL-4 and/or IL-13 and their uses
EP2573118A1 (en) 2007-10-15 2013-03-27 Sanofi Antibodies that bind IL-4 and/or IL-13 and their uses
EP2573116A1 (en) 2007-10-15 2013-03-27 Sanofi Antibodies that bind IL-4 and/or IL-13 and their uses
EP2573115A1 (en) 2007-10-15 2013-03-27 Sanofi Antibodies that bind IL-4 and/or IL-13 and their uses
US9738728B2 (en) 2007-10-15 2017-08-22 Sanofi Antibodies that bind IL-4 and/or IL-13 and their uses
EP2573119A1 (en) 2007-10-15 2013-03-27 Sanofi Antibodies that bind IL-4 and/or IL-13 and their uses
EP2574626A1 (en) 2007-10-15 2013-04-03 Sanofi Antibodies that bind IL-4 and/or IL-13 and their uses
US9732162B2 (en) 2007-10-15 2017-08-15 Sanofi Antibodies that bind IL-4 and/or IL-13 and their uses
EP2574629A1 (en) 2007-10-15 2013-04-03 Sanofi Antibodies that bind il-4 and/or il-13 and their uses
EP2574630A1 (en) 2007-10-15 2013-04-03 Sanofi Antibodies that bind il-4 and/or il-13 and their uses
EP2573117A1 (en) 2007-10-15 2013-03-27 Sanofi Antibodies that bind IL-4 and/or IL-13 and their uses
JP2011502126A (en) * 2007-10-31 2011-01-20 ゼンコア インコーポレイテッド Fc variant having mutant binding to FcRn
US8795667B2 (en) 2007-12-19 2014-08-05 Macrogenics, Inc. Compositions for the prevention and treatment of smallpox
EP3211010A1 (en) 2007-12-21 2017-08-30 Medimmune Limited Binding members for interleukin-4 receptor alpha (il-4r) - 173
EP2604628A2 (en) 2007-12-21 2013-06-19 Medimmune Limited Binding members for interleukin-4 receptor alpha (IL-4R) - 173
JP2011507963A (en) * 2007-12-26 2011-03-10 ゼンコア インコーポレイテッド Fc variant having mutant binding to FcRn
US10479831B2 (en) 2008-04-02 2019-11-19 Macrogenics, Inc BCR-complex-specific antibodies and methods of using same
US8993730B2 (en) 2008-04-02 2015-03-31 Macrogenics, Inc. BCR-complex-specific antibodies and methods of using same
US10131713B2 (en) 2008-04-02 2018-11-20 Macrogenics, Inc. HER2/neu-specific antibodies and methods of using same
US9695236B2 (en) 2008-04-02 2017-07-04 Macrogenics, Inc. BCR-complex-specific antibodies and methods of using same
US9243069B2 (en) 2008-04-02 2016-01-26 Macrogenics, Inc. HER2/neu-specific antibodies and methods of using the same
US9469692B2 (en) 2008-04-02 2016-10-18 Macrogenics, Inc. HER2/neu-specific antibodies and methods of using same
US11028183B2 (en) 2008-04-02 2021-06-08 Macrogenics, Inc. HER2/neu-specific antibodies and methods of using same
EP2837388A1 (en) 2008-08-05 2015-02-18 Novartis AG Compositions and methods for antibodies targeting complement protein C5
WO2010015608A1 (en) 2008-08-05 2010-02-11 Novartis Ag Compositions and methods for antibodies targeting complement protein c5
EP2815766A1 (en) 2008-08-05 2014-12-24 Novartis AG Compositions and methods for antibodies targeting complement protein C5
WO2010027364A1 (en) 2008-09-07 2010-03-11 Glyconex Inc. Anti-extended type i glycosphingolipid antibody, derivatives thereof and use
EP2927244A1 (en) 2008-09-19 2015-10-07 MedImmune, LLC Antibodies directed to DLL4 and uses thereof
US9200074B2 (en) 2008-11-07 2015-12-01 Medimmune Limited Antibodies to IL-1 R1 and methods of making them
US8741604B2 (en) 2008-11-07 2014-06-03 Medimmune Limited Nucleic acid molecule encoding a specific IL-1R1 antibody
US8298533B2 (en) 2008-11-07 2012-10-30 Medimmune Limited Antibodies to IL-1R1
WO2010056804A1 (en) 2008-11-12 2010-05-20 Medimmune, Llc Antibody formulation
US8775090B2 (en) 2008-12-12 2014-07-08 Medimmune, Llc Crystals and structure of a human IgG Fc variant with enhanced FcRn binding
WO2010070346A2 (en) 2008-12-18 2010-06-24 Medimmune Limited BINDING MEMBERS FOR INTERLEUKIN-4 RECEPTOR ALPHA (IL-4Ra) - 836
WO2010072740A2 (en) 2008-12-23 2010-07-01 Astrazeneca Ab TARGETED BINDING AGENTS DIRECTED TO α5β1 AND USES THEREOF
WO2010078526A1 (en) 2008-12-31 2010-07-08 Biogen Idec Ma Inc. Anti-lymphotoxin antibodies
US8852608B2 (en) 2009-02-02 2014-10-07 Medimmune, Llc Antibodies against and methods for producing vaccines for respiratory syncytial virus
US9499590B2 (en) 2009-02-02 2016-11-22 Medimmune, Llc Antibodies against and methods for producing vaccines for respiratory syncytial virus
WO2011020024A2 (en) 2009-08-13 2011-02-17 The Johns Hopkins University Methods of modulating immune function
EP3381937A2 (en) 2009-08-13 2018-10-03 The Johns Hopkins University Methods of modulating immune function
US9376672B2 (en) 2009-08-24 2016-06-28 Amunix Operating Inc. Coagulation factor IX compositions and methods of making and using same
US9758776B2 (en) 2009-08-24 2017-09-12 Amunix Operating Inc. Coagulation factor IX compositions and methods of making and using same
US11401348B2 (en) 2009-09-02 2022-08-02 Xencor, Inc. Heterodimeric Fc variants
US9283274B2 (en) 2009-10-06 2016-03-15 Medimmune Limited RSV specific binding molecule
US10723786B2 (en) 2009-10-06 2020-07-28 Medimmune, Limited RSV-specific binding molecule
US10035843B2 (en) 2009-10-06 2018-07-31 Medimmune Limited RSV-specific binding molecule
WO2011044368A1 (en) 2009-10-07 2011-04-14 Macrogenics, Inc. Fc region-containing polypeptides that exhibit improved effector function due to alterations of the extent of fucosylation, and methods for their use
US9096877B2 (en) 2009-10-07 2015-08-04 Macrogenics, Inc. Fc region-containing polypeptides that exhibit improved effector function due to alterations of the extent of fucosylation, and methods for their use
EP3202898A1 (en) 2009-11-02 2017-08-09 University of Washington Therapeutic nuclease compositions and methods
US8841416B2 (en) 2009-11-02 2014-09-23 University Of Washington Therapeutic nuclease compositions and methods
US11306297B2 (en) 2009-11-02 2022-04-19 University Of Washington Therapeutic nuclease compositions and methods
US10000745B2 (en) 2009-11-02 2018-06-19 University Of Washington Therapeutic nuclease compositions and methods
EP3460056A1 (en) 2009-11-02 2019-03-27 University Of Washington Therapeutic nuclease compositions and methods
WO2011053982A2 (en) 2009-11-02 2011-05-05 University Of Washington Therapeutic nuclease compositions and methods
US9790479B2 (en) 2009-11-02 2017-10-17 University Of Washington Therapeutic nuclease compositions and methods
EP3279215A1 (en) 2009-11-24 2018-02-07 MedImmune Limited Targeted binding agents against b7-h1
US9475881B2 (en) 2010-01-19 2016-10-25 Xencor, Inc. Antibody variants with enhanced complement activity
US9896508B2 (en) 2010-03-04 2018-02-20 Macrogenics, Inc. Antibodies reactive with B7-H3 and uses thereof
US9150656B2 (en) 2010-03-04 2015-10-06 Macrogenics, Inc. Antibodies reactive with B7-H3, immunologically active fragments thereof and uses thereof
US10683364B2 (en) 2010-03-04 2020-06-16 Macrogenics, Inc. Antibodies reactive with B7-H3, immunologically active fragments thereof and uses thereof
US9714295B2 (en) 2010-03-04 2017-07-25 Macrogenics, Inc. Antibodies reactive with B7-H3, immunologically active fragments thereof and uses thereof
US9714296B2 (en) 2010-03-04 2017-07-25 Macrogenics, Inc. Antibodies reactive with B7-H3, immunologically active fragments thereof and uses thereof
US9441049B2 (en) 2010-03-04 2016-09-13 Macrogenics, Inc. Antibodies reactive with B7-H3 and uses thereof
US10730945B2 (en) 2010-03-04 2020-08-04 Macrogenics, Inc. Antibodies reactive with B7-H3 and users thereof
WO2011138392A1 (en) 2010-05-06 2011-11-10 Novartis Ag Compositions and methods of use for therapeutic low density lipoprotein -related protein 6 (lrp6) antibodies
EP3345926A1 (en) 2010-05-06 2018-07-11 Novartis AG Compositions and methods of use for therapeutic low density lipoprotein-related protein 6 (lrp6) antibodies
EP4234698A2 (en) 2010-05-06 2023-08-30 Novartis AG Compositions and methods of use for therapeutic low density lipoprotein-related protein 6 (lrp6) antibodies
WO2011138391A1 (en) 2010-05-06 2011-11-10 Novartis Ag Compositions and methods of use for therapeutic low density lipoprotein - related protein 6 (lrp6) multivalent antibodies
US9856468B2 (en) 2010-07-09 2018-01-02 Bioverativ Therapeutics Inc. Processable single chain molecules and polypeptides made using same
WO2012006633A1 (en) 2010-07-09 2012-01-12 Biogen Idec Hemophilia Inc. Chimeric clotting factors
WO2012006635A1 (en) 2010-07-09 2012-01-12 Biogen Idec Hemophilia Inc. Processable single chain molecules and polypeptides made using same
EP3560962A1 (en) 2010-07-09 2019-10-30 Bioverativ Therapeutics Inc. Processable single chain molecules and polypeptides made using same
US10968442B2 (en) 2010-07-09 2021-04-06 Bioverativ Therapeutics Inc. Chimeric clotting factors
US10927362B2 (en) 2010-07-09 2021-02-23 Bioverativ Therapeutics Inc. Processable single chain molecules and polypeptides made using same
WO2012022814A1 (en) 2010-08-20 2012-02-23 Novartis Ag Antibodies for epidermal growth factor receptor 3 (her3)
WO2012069466A1 (en) 2010-11-24 2012-05-31 Novartis Ag Multispecific molecules
WO2012083370A1 (en) 2010-12-22 2012-06-28 Cephalon Australia Pty Ltd Modified antibody with improved half-life
US11008389B2 (en) 2011-03-16 2021-05-18 Sanofi Uses of a dual V region antibody-like protein
US8969526B2 (en) 2011-03-29 2015-03-03 Roche Glycart Ag Antibody Fc variants
EP3403672A1 (en) 2011-04-20 2018-11-21 Medlmmune, LLC Antibodies and other molecules that bind b7-h1 and pd-1
WO2012145493A1 (en) 2011-04-20 2012-10-26 Amplimmune, Inc. Antibodies and other molecules that bind b7-h1 and pd-1
US11034944B2 (en) 2011-04-29 2021-06-15 University Of Washington Therapeutic nuclease compositions and methods
US10202588B2 (en) 2011-04-29 2019-02-12 The University Of Washington Therapeutic nuclease compositions and methods
US8937157B2 (en) 2011-04-29 2015-01-20 University Of Washington Therapeutic nuclease compositions and methods
WO2012149440A2 (en) 2011-04-29 2012-11-01 University Of Washington Therapeutic nuclease compositions and methods
EP3449933A1 (en) 2011-04-29 2019-03-06 University of Washington Therapeutic nuclease compositions and methods
US9376495B2 (en) 2011-05-21 2016-06-28 Macrogenics, Inc. Deimmunized serum-binding domains and their use in extending serum half-life
US9486507B2 (en) 2011-06-10 2016-11-08 Biogen Ma Inc. Pro-coagulant compounds and methods of use thereof
EP3527218A1 (en) 2011-06-10 2019-08-21 Bioverativ Therapeutics Inc. Pro-coagulant compounds and methods of use thereof
WO2012172495A1 (en) 2011-06-14 2012-12-20 Novartis Ag Compositions and methods for antibodies targeting tem8
WO2013012733A1 (en) 2011-07-15 2013-01-24 Biogen Idec Ma Inc. Heterodimeric fc regions, binding molecules comprising same, and methods relating thereto
WO2013025779A1 (en) 2011-08-15 2013-02-21 Amplimmune, Inc. Anti-b7-h4 antibodies and their uses
US11186638B2 (en) 2011-09-12 2021-11-30 Genzyme Corporation Anti-αβTCR antibody
WO2013039954A1 (en) 2011-09-14 2013-03-21 Sanofi Anti-gitr antibodies
EP3252075A1 (en) 2011-11-04 2017-12-06 Novartis AG Low density lipoprotein-related protein 6 (lrp6) - half life extender constructs
EP3290442A1 (en) 2011-11-04 2018-03-07 Novartis AG Low density lipoprotein-related protein 6 (lrp6) half-life extender constructs
WO2013067355A1 (en) 2011-11-04 2013-05-10 Novartis Ag Low density lipoprotein-related protein 6 (lrp6) - half life extender constructs
WO2013084147A2 (en) 2011-12-05 2013-06-13 Novartis Ag Antibodies for epidermal growth factor receptor 3 (her3)
WO2013085972A1 (en) 2011-12-05 2013-06-13 X-Body, Inc. Pdgf receptor beta binding polypeptides
US11136398B2 (en) 2011-12-05 2021-10-05 X-Body, Inc. PDGF receptor beta binding polypeptides
WO2013084148A2 (en) 2011-12-05 2013-06-13 Novartis Ag Antibodies for epidermal growth factor receptor 3 (her3) directed to domain ii of her3
EP3712173A1 (en) 2011-12-05 2020-09-23 X-Body, Inc. Pdgf receptor beta binding polypeptides
EP3590538A1 (en) 2011-12-05 2020-01-08 Novartis AG Antibodies for epidermal growth factor receptor 3 (her3)
EP3330288A1 (en) 2011-12-21 2018-06-06 Novartis AG Compositions and methods for antibodies targeting factor p
WO2013093762A1 (en) 2011-12-21 2013-06-27 Novartis Ag Compositions and methods for antibodies targeting factor p
US11370827B2 (en) 2012-01-12 2022-06-28 Bioverativ Therapeutics Inc. Chimeric factor VIII polypeptides and uses thereof
EP3505179A1 (en) 2012-01-12 2019-07-03 Bioverativ Therapeutics Inc. Chimeric factor viii polypeptides and uses thereof
US10421798B2 (en) 2012-02-15 2019-09-24 Bioverativ Therapeutics Inc. Factor VIII compositions and methods of making and using same
US10370430B2 (en) 2012-02-15 2019-08-06 Bioverativ Therapeutics Inc. Recombinant factor VIII proteins
US11685771B2 (en) 2012-02-15 2023-06-27 Bioverativ Therapeutics Inc. Recombinant factor VIII proteins
US9592289B2 (en) 2012-03-26 2017-03-14 Sanofi Stable IgG4 based binding agent formulations
US10525130B2 (en) 2012-03-26 2020-01-07 Sanofi Stable IGG4 based binding agent formulations
WO2013148296A1 (en) 2012-03-28 2013-10-03 Sanofi Antibodies to bradykinin b1 receptor ligands
EP3246339A1 (en) 2012-03-28 2017-11-22 Sanofi Antibodies to bradykinin b1 receptor ligands
WO2013169657A1 (en) 2012-05-07 2013-11-14 Sanofi Methods for preventing biofilm formation
WO2013175276A1 (en) 2012-05-23 2013-11-28 Argen-X B.V Il-6 binding molecules
US11827701B2 (en) 2012-05-23 2023-11-28 argenx BV IL-6 binding molecules
WO2013175427A1 (en) 2012-05-23 2013-11-28 Argen-X B.V. Il-6 binding molecules
US11117959B2 (en) 2012-05-23 2021-09-14 Argenx Bvba IL-6 binding molecules
US10183995B2 (en) 2012-05-23 2019-01-22 Argen-X N.V. IL-6 binding molecules
WO2013185113A1 (en) 2012-06-08 2013-12-12 Biogen Idec Ma Inc. Procoagulant compounds
US10202595B2 (en) 2012-06-08 2019-02-12 Bioverativ Therapeutics Inc. Chimeric clotting factors
US10287564B2 (en) 2012-06-08 2019-05-14 Bioverativ Therapeutics Inc. Procoagulant compounds
US11261437B2 (en) 2012-06-08 2022-03-01 Bioverativ Therapeutics Inc. Procoagulant compounds
WO2013185114A2 (en) 2012-06-08 2013-12-12 Biogen Idec Ma Inc. Chimeric clotting factors
EP3693000A1 (en) 2012-06-08 2020-08-12 Bioverativ Therapeutics Inc. Procoagulant compounds
EP4079316A1 (en) 2012-06-08 2022-10-26 Bioverativ Therapeutics Inc. Procoagulant compounds
US11168316B2 (en) 2012-06-08 2021-11-09 Bioverativ Therapeutics, Inc. Chimeric clotting factors
US10919975B2 (en) 2012-06-27 2021-02-16 Amgen Inc. Anti-mesothelin binding proteins
US11866508B2 (en) 2012-06-27 2024-01-09 Amgen Inc. Anti-mesothelin binding proteins
US10100121B2 (en) 2012-06-27 2018-10-16 Amgen Inc. Anti-mesothelin binding proteins
EP3404105A1 (en) 2012-07-06 2018-11-21 Bioverativ Therapeutics Inc. Cell line expressing single chain factor viii polypeptides and uses thereof
US10023628B2 (en) 2012-07-06 2018-07-17 Bioverativ Therapeutics Inc. Cell line expressing single chain factor VIII polypeptides and uses thereof
EP3674410A1 (en) 2012-07-11 2020-07-01 Bioverativ Therapeutics Inc. Factor viii complex with xten and von willebrand factor protein, and uses thereof
US11091534B2 (en) 2012-07-11 2021-08-17 Bioverativ Therapeutics Inc. Factor VIII complex with XTEN and von Willebrand Factor protein, and uses thereof
US10138291B2 (en) 2012-07-11 2018-11-27 Bioverativ Therapeutics Inc. Factor VIII complex with XTEN and von Willebrand Factor protein, and uses thereof
EP4269431A1 (en) 2012-07-11 2023-11-01 Bioverativ Therapeutics Inc. Factor viii complex with xten and von willebrand factor protein, and uses thereof
US10683345B2 (en) 2012-07-13 2020-06-16 Roche Glycart Ag Bispecific anti-VEGF/anti-ANG-2 antibodies and their use in the treatment of ocular vascular diseases
US9695233B2 (en) 2012-07-13 2017-07-04 Roche Glycart Ag Bispecific anti-VEGF/anti-ANG-2 antibodies and their use in the treatment of ocular vascular diseases
US9790268B2 (en) 2012-09-12 2017-10-17 Genzyme Corporation Fc containing polypeptides with altered glycosylation and reduced effector function
EP4223783A2 (en) 2012-09-12 2023-08-09 Genzyme Corporation Fc containing polypeptides with altered glycosylation and reduced effector function
US10836813B2 (en) 2012-09-12 2020-11-17 Genzyme Corporation Fc containing polypeptides with altered glycosylation and reduced effector function
WO2014074905A1 (en) 2012-11-08 2014-05-15 Eleven Biotherapeutics, Inc. Il-6 antagonists and uses thereof
US11459386B2 (en) 2012-11-08 2022-10-04 Sesen Bio, Inc. IL-6 antagonists and uses thereof
EP3489258A1 (en) 2012-11-08 2019-05-29 Eleven Biotherapeutics, Inc. Il-6 antagonists and uses thereof
US9951130B2 (en) 2012-11-08 2018-04-24 Eleven Biotherapeutics, Inc. IL-6 antagonists and uses thereof
WO2014084859A1 (en) 2012-11-30 2014-06-05 Novartis Ag Molecules and methods for modulating tmem16a activities
WO2014089111A1 (en) 2012-12-05 2014-06-12 Novartis Ag Compositions and methods for antibodies targeting epo
EP3851454A1 (en) 2012-12-05 2021-07-21 Novartis AG Compositions and methods for antibodies targeting epo
WO2014100483A1 (en) 2012-12-19 2014-06-26 Amplimmune, Inc. Anti-human b7-h4 antibodies and their uses
WO2014100823A1 (en) 2012-12-21 2014-06-26 Amplimmune, Inc. Anti-h7cr antibodies
US10370431B2 (en) 2013-02-15 2019-08-06 Bioverativ Therapeutics Inc. Optimized factor VIII gene
US11787851B2 (en) 2013-02-15 2023-10-17 Bioverativ Therapeutics Inc. Optimized factor VIII gene
WO2014127215A1 (en) 2013-02-15 2014-08-21 Biogen Idec Ma Inc. Optimized factor viii gene
EP4223772A2 (en) 2013-02-15 2023-08-09 Bioverativ Therapeutics Inc. Optimized factor viii gene
EP3889173A1 (en) 2013-02-15 2021-10-06 Bioverativ Therapeutics Inc. Optimized factor viii gene
US9487587B2 (en) 2013-03-05 2016-11-08 Macrogenics, Inc. Bispecific molecules that are immunoreactive with immune effector cells of a companion animal that express an activating receptor and cells that express B7-H3 and uses thereof
EP4098663A1 (en) 2013-03-11 2022-12-07 Genzyme Corporation Hyperglycosylated binding polypeptides
US9580511B2 (en) 2013-03-11 2017-02-28 Genzyme Corporation Site-specific antibody-drug conjugation through glycoengineering
US11807690B2 (en) 2013-03-11 2023-11-07 Genzyme Corporation Hyperglycosylated binding polypeptides
WO2014164534A2 (en) 2013-03-11 2014-10-09 Genzyme Corporation Site-specific antibody-drug conjugation through glycoengineering
WO2014164503A1 (en) 2013-03-11 2014-10-09 Genzyme Corporation Hyperglycosylated binding polypeptides
EP3424956A1 (en) 2013-03-11 2019-01-09 Genzyme Corporation Hyperglycosylated binding polypeptides
US9701753B2 (en) 2013-03-11 2017-07-11 Genzyme Corporation Hyperglycosylated binding polypeptides
US11130816B2 (en) 2013-03-11 2021-09-28 Genzyme Corporation Site-specific antibody-drug conjugation through glycoengineering
EP4063389A2 (en) 2013-03-11 2022-09-28 Genzyme Corporation Site-specific antibody-drug conjugation through glycoengineering
US10214589B2 (en) 2013-03-11 2019-02-26 Genzyme Corporation Site-specific antibody-drug conjugation through glycoengineering
US10494439B2 (en) 2013-03-11 2019-12-03 Genzyme Corporation Hyperglycosylated binding polypeptides
US9908938B2 (en) 2013-03-14 2018-03-06 Macrogenics, Inc. Bispecific molecules that are immunoreactive with immune effector cells that express an activating receptor and an antigen expressed by a cell infected by a virus and uses thereof
EP3611189A1 (en) 2013-03-14 2020-02-19 Novartis AG Antibodies against notch 3
US11421031B2 (en) 2013-03-14 2022-08-23 Macrogenics, Inc. Bispecific molecules that are immunoreactive with immune effector cells that express an activating receptor and an antigen expressed by a cell infected by a virus and uses thereof
US10730947B2 (en) 2013-03-14 2020-08-04 Macrogenics, Inc. Bispecific molecules that are immunoreactive with immune effector cells that express an activating receptor and an antigen expressed by a cell infected by a virus and uses thereof
WO2014159239A2 (en) 2013-03-14 2014-10-02 Novartis Ag Antibodies against notch 3
US11642398B2 (en) 2013-03-15 2023-05-09 Bioverativ Therapeutics Inc. Factor IX polypeptide formulations
EP3473272A1 (en) 2013-03-29 2019-04-24 Alexion Pharmaceuticals, Inc. Compositions and methods for increasing the serum half-life of a therapeutic agent targeting complement c5
WO2014160958A1 (en) 2013-03-29 2014-10-02 Alexion Pharmaceuticals, Inc. Compositions and methods for increasing the serum half-life of a therapeutic agent targeting complement c5
WO2014190356A2 (en) 2013-05-24 2014-11-27 Amplimmune, Inc. Anti-b7-h5 antibodies and their uses
WO2014205302A2 (en) 2013-06-21 2014-12-24 Novartis Ag Lectin-like oxidized ldl receptor1 antibodies and methods of use
WO2014205300A2 (en) 2013-06-21 2014-12-24 Novartis Ag Lectin-like oxidized ldl receptor1 antibodies and methods of use
EP3875106A1 (en) 2013-08-08 2021-09-08 Bioverativ Therapeutics Inc. Purification of chimeric fviii molecules
US10947269B2 (en) 2013-08-08 2021-03-16 Bioverativ Therapeutics Inc. Purification of chimeric FVIII molecules
US10344092B2 (en) 2013-08-09 2019-07-09 Macrogenics, Inc. Bi-specific monovalent Fc diabodies that are capable of binding CD32B and CD79b and uses thereof
US11384149B2 (en) 2013-08-09 2022-07-12 Macrogenics, Inc. Bi-specific monovalent Fc diabodies that are capable of binding CD32B and CD79b and uses thereof
US9845363B2 (en) 2013-08-13 2017-12-19 Sanofi Antibodies to plasminogen activator inhibitor-1 (PAI-1) and uses thereof
EP3620472A1 (en) 2013-08-13 2020-03-11 Sanofi Antibodies to plasminogen activator inhibitor-1 (pai-1) and uses thereof
US10548953B2 (en) 2013-08-14 2020-02-04 Bioverativ Therapeutics Inc. Factor VIII-XTEN fusions and uses thereof
WO2015023891A2 (en) 2013-08-14 2015-02-19 Biogen Idec Ma Inc. Factor viii-xten fusions and uses thereof
US10858430B2 (en) 2013-08-23 2020-12-08 Macrogenics, Inc. Bi-specific monovalent diabodies that are capable of binding to gpA33 and CD3, and uses thereof
US9822181B2 (en) 2013-08-23 2017-11-21 Macrogenics, Inc. Bi-specific monovalent diabodies that are capable of binding CD123 and CD3, and uses thereof
US10787521B2 (en) 2013-08-23 2020-09-29 Macrogenics, Inc. Bi-specific monovalent diabodies that are capable of binding CD123 and CD3, and uses thereof
US9932400B2 (en) 2013-08-23 2018-04-03 Macrogenics, Inc. Bi-specific monovalent diabodies that are capable of binding to gpA33 and CD3, and uses thereof
EP3903599A1 (en) 2013-09-25 2021-11-03 Bioverativ Therapeutics Inc. On-column viral inactivation methods
US11578098B2 (en) 2013-09-25 2023-02-14 Bioverativ Therapeutics Inc. On-column viral inactivation methods
US10611794B2 (en) 2013-09-25 2020-04-07 Bioverativ Therapeutics Inc. On-column viral inactivation methods
US10988745B2 (en) 2013-10-31 2021-04-27 Resolve Therapeutics, Llc Therapeutic nuclease-albumin fusions and methods
WO2015066557A1 (en) 2013-10-31 2015-05-07 Resolve Therapeutics, Llc Therapeutic nuclease molecules with altered glycosylation and methods
US10584147B2 (en) 2013-11-08 2020-03-10 Biovertiv Therapeutics Inc. Procoagulant fusion compound
EP4176894A1 (en) 2014-01-10 2023-05-10 Bioverativ Therapeutics Inc. Factor viii chimeric proteins and uses thereof
WO2015106052A1 (en) 2014-01-10 2015-07-16 Biogen Ma Inc. Factor viii chimeric proteins and uses thereof
US11192936B2 (en) 2014-01-10 2021-12-07 Bioverativ Therapeutics Inc. Factor VIII chimeric proteins and uses thereof
EP3095795A1 (en) 2014-03-07 2016-11-23 Alexion Pharmaceuticals, Inc. Anti-c5 antibodies having improved pharmacokinetics
US10584164B2 (en) 2014-03-07 2020-03-10 Alexion Pharmaceuticals, Inc. Methods of treating atypical hemolytic uremic syndrome and paroxysmal nocturnal hemoglobinuria with anti-C5 antibodies
US9803007B1 (en) 2014-03-07 2017-10-31 Alexion Pharmaceuticals, Inc. Anti-C5 antibodies having improved pharmacokinetics
US9663574B2 (en) 2014-03-07 2017-05-30 Alexion Pharmaceuticals, Inc. Anti-C5 antibodies having improved pharmacokinetics
US9079949B1 (en) 2014-03-07 2015-07-14 Alexion Pharmaceuticals, Inc. Anti-C5 antibodies having improved pharmacokinetics
US9206251B2 (en) 2014-03-07 2015-12-08 Alexion Pharmaceuticals, Inc. Nucleic acids encoding anti-C5 antibodies having improved pharmacokinetics
WO2015134894A1 (en) 2014-03-07 2015-09-11 Alexion Pharmaceuticals, Inc. Anti-c5 antibodies having improved pharmacokinetics
US11434280B2 (en) 2014-03-07 2022-09-06 Alexion Pharmaceuticals, Inc. Anti-C5 antibodies having improved pharmacokinetics
US9107861B1 (en) 2014-03-07 2015-08-18 Alexion Pharmaceuticals, Inc. Methods of treating C5 mediated complement-associated conditions with anti-C5 antibodies having improved pharmacokinetics
EP3594235A1 (en) 2014-03-07 2020-01-15 Alexion Pharmaceuticals, Inc. Anti-c5 antibodies having improved pharmacokinetics
US9371377B2 (en) 2014-03-07 2016-06-21 Alexion Pharmaceuticals, Inc. Anti-C5 antibodies having improved pharmacokinetics
US10227400B2 (en) 2014-03-07 2019-03-12 Alexion Pharmaceuticals, Inc. Methods of treating atypical hemolytic uremic syndrome with anti-C5 antibodies
US11697690B2 (en) 2014-03-19 2023-07-11 Genzyme Corporation Site-specific glycoengineering of targeting moieties
US10995148B2 (en) 2014-03-19 2021-05-04 Genzyme Corporation Site-specific glycoengineering of targeting moieties
EP4015535A1 (en) 2014-03-19 2022-06-22 Genzyme Corporation Site-specific glycoengineering of targeting moieties
WO2015143271A1 (en) 2014-03-21 2015-09-24 X-Body, Inc. Bi-specific antigen-binding polypeptides
EP3712176A1 (en) 2014-03-21 2020-09-23 X-Body, Inc. Bi-specific antigen-binding polypeptides
EP3888690A2 (en) 2014-05-16 2021-10-06 MedImmune, LLC Molecules with altered neonate fc receptor binding having enhanced therapeutic and diagnostic properties
WO2015175874A2 (en) 2014-05-16 2015-11-19 Medimmune, Llc Molecules with altered neonate fc receptor binding having enhanced therapeutic and diagnostic properties
EP3498295A1 (en) 2014-05-28 2019-06-19 Agenus Inc. Anti-gitr antibodies and methods of use thereof
US10577426B2 (en) 2014-05-28 2020-03-03 Agenus Inc. Anti-GITR antibodies and methods of use thereof
US11897962B2 (en) 2014-05-28 2024-02-13 Agenus Inc. Anti-GITR antibodies and methods of use thereof
US10280226B2 (en) 2014-05-28 2019-05-07 Agenus Inc. Anti-GITR antibodies and methods of use thereof
WO2015184099A1 (en) 2014-05-28 2015-12-03 4-Antibody Ag Anti-gitr antibodies and methods of use thereof
US10800849B2 (en) 2014-05-28 2020-10-13 Agenus Inc. Anti-GITR antibodies and methods of use thereof
US10155818B2 (en) 2014-05-28 2018-12-18 Agenus Inc. Anti-GITR antibodies and methods of use thereof
US10829559B2 (en) 2014-05-28 2020-11-10 Agenus Inc. Anti-GITR antibodies and methods of use thereof
US11401335B2 (en) 2014-05-28 2022-08-02 Agenus Inc. Anti-GITR antibodies and methods of use thereof
US11008561B2 (en) 2014-06-30 2021-05-18 Bioverativ Therapeutics Inc. Optimized factor IX gene
US8980273B1 (en) 2014-07-15 2015-03-17 Kymab Limited Method of treating atopic dermatitis or asthma using antibody to IL4RA
US8986691B1 (en) 2014-07-15 2015-03-24 Kymab Limited Method of treating atopic dermatitis or asthma using antibody to IL4RA
WO2016020880A2 (en) 2014-08-07 2016-02-11 Novartis Ag Angiopoietin-like 4 antibodies and methods of use
WO2016020882A2 (en) 2014-08-07 2016-02-11 Novartis Ag Angiopoetin-like 4 (angptl4) antibodies and methods of use
EP4122957A1 (en) 2014-08-07 2023-01-25 Novartis AG Angiopoietin-like 4 antibodies and methods of use
US9975966B2 (en) 2014-09-26 2018-05-22 Chugai Seiyaku Kabushiki Kaisha Cytotoxicity-inducing theraputic agent
US11001643B2 (en) 2014-09-26 2021-05-11 Chugai Seiyaku Kabushiki Kaisha Cytotoxicity-inducing therapeutic agent
WO2016046301A1 (en) 2014-09-26 2016-03-31 Bayer Pharma Aktiengesellschaft Stabilized adrenomedullin derivatives and use thereof
US10717778B2 (en) 2014-09-29 2020-07-21 Duke University Bispecific molecules comprising an HIV-1 envelope targeting arm
WO2016057841A1 (en) 2014-10-08 2016-04-14 Novartis Ag Compositions and methods of use for augmented immune response and cancer therapy
WO2016057846A1 (en) 2014-10-08 2016-04-14 Novartis Ag Compositions and methods of use for augmented immune response and cancer therapy
US10064952B2 (en) 2014-10-09 2018-09-04 Genzyme Corporation Glycoengineered antibody drug conjugates
US11160874B2 (en) 2014-10-09 2021-11-02 Genzyme Corporation Glycoengineered antibody drug conjugates
EP3799887A1 (en) 2014-10-09 2021-04-07 Genzyme Corporation Glycoengineered antibody drug conjugates
WO2016061286A2 (en) 2014-10-14 2016-04-21 Halozyme, Inc. Compositions of adenosine deaminase-2 (ada2), variants thereof and methods of using same
US9969998B2 (en) 2014-10-14 2018-05-15 Halozyme, Inc. Compositions of adenosine deaminase-2 (ADA2), variants thereof and methods of using same
US11584923B2 (en) 2014-10-14 2023-02-21 Halozyme, Inc. Compositions of adenosine deaminase-2 (ADA2), variants thereof and methods of using same
US11142571B2 (en) 2014-11-07 2021-10-12 Sesen Bio, Inc. IL-6 antibodies
EP4268843A2 (en) 2014-11-07 2023-11-01 F. Hoffmann-La Roche Ltd Improved il-6 antibodies
EP3632931A1 (en) 2014-11-07 2020-04-08 Sesen Bio, Inc. Improved il-6 antibodies
WO2016081748A2 (en) 2014-11-21 2016-05-26 Bristol-Myers Squibb Company Antibodies against cd73 and uses thereof
EP3725808A1 (en) 2014-11-21 2020-10-21 Bristol-Myers Squibb Company Antibodies against cd73 and uses thereof
EP3789399A1 (en) 2014-11-21 2021-03-10 Bristol-Myers Squibb Company Antibodies comprising modified heavy constant regions
WO2016094834A2 (en) 2014-12-12 2016-06-16 Alexion Pharmaceuticals, Inc. A method for treating a complement mediated disorder caused by an infectious agent in a patient
WO2016098079A2 (en) 2014-12-19 2016-06-23 Novartis Ag Compositions and methods for antibodies targeting bmp6
WO2016106221A1 (en) 2014-12-22 2016-06-30 The Rockefeller University Anti-mertk agonistic antibodies and uses thereof
EP3789039A1 (en) 2014-12-22 2021-03-10 The Rockefeller University Anti-mertk agonistic antibodies and uses thereof
EP4249066A2 (en) 2014-12-23 2023-09-27 Bristol-Myers Squibb Company Antibodies to tigit
WO2016115345A1 (en) 2015-01-14 2016-07-21 The Brigham And Women's Hospital, Treatment of cancer with anti-lap monoclonal antibodies
WO2016123454A1 (en) 2015-01-29 2016-08-04 Board Of Trustees Of Miching State University Cryptic polypeptides and uses thereof
WO2016196228A1 (en) 2015-05-29 2016-12-08 Bristol-Myers Squibb Company Antibodies against ox40 and uses thereof
WO2016193872A2 (en) 2015-06-05 2016-12-08 Novartis Ag Antibodies targeting bone morphogenetic protein 9 (bmp9) and methods therefor
EP4303235A2 (en) 2015-06-08 2024-01-10 MacroGenics, Inc. Lag-3-binding moleculkes and methods of use thereof
US11858991B2 (en) 2015-06-08 2024-01-02 Macrogenics, Inc. LAG-3-binding molecules and methods of use thereof
US11072653B2 (en) 2015-06-08 2021-07-27 Macrogenics, Inc. LAG-3-binding molecules and methods of use thereof
WO2016207858A1 (en) 2015-06-26 2016-12-29 Novartis Ag Factor xi antibodies and methods of use
WO2017004016A1 (en) 2015-06-29 2017-01-05 The Rockefeller University Antibodies to cd40 with enhanced agonist activity
US11623959B2 (en) 2015-07-30 2023-04-11 Macrogenics, Inc. PD-1-binding molecules and methods of use thereof
EP3981792A1 (en) 2015-07-30 2022-04-13 MacroGenics, Inc. Pd-1-binding molecules and methods of use thereof
US10577422B2 (en) 2015-07-30 2020-03-03 Macrogenics, Inc. PD-1-binding molecules and methods of use thereof
WO2017019846A1 (en) 2015-07-30 2017-02-02 Macrogenics, Inc. Pd-1-binding molecules and methods use thereof
EP3456346A1 (en) 2015-07-30 2019-03-20 MacroGenics, Inc. Pd-1 and lag-3 binding molecules and methods of use thereof
WO2017021893A1 (en) 2015-08-03 2017-02-09 Novartis Ag Methods of treating fgf21-associated disorders
US10745680B2 (en) 2015-08-03 2020-08-18 Bioverativ Therapeutics Inc. Factor IX fusion proteins and methods of making and using same
WO2017040790A1 (en) 2015-09-01 2017-03-09 Agenus Inc. Anti-pd-1 antibodies and methods of use thereof
EP3842457A1 (en) 2015-09-09 2021-06-30 Novartis AG Thymic stromal lymphopoietin (tslp)-binding molecules and methods of using the molecules
WO2017042701A1 (en) 2015-09-09 2017-03-16 Novartis Ag Thymic stromal lymphopoietin (tslp)-binding antibodies and methods of using the antibodies
WO2017046746A1 (en) 2015-09-15 2017-03-23 Acerta Pharma B.V. Therapeutic combinations of a btk inhibitor and a gitr binding molecule, a 4-1bb agonist, or an ox40 agonist
US10358497B2 (en) 2015-09-29 2019-07-23 Amgen Inc. Methods of treating cardiovascular disease with an ASGR inhibitor
US11066472B2 (en) 2015-09-29 2021-07-20 Amgen Inc. Methods of treating cardiovascular disease with an anti-ASGR antibody or binding fragments thereof
US11174315B2 (en) 2015-10-08 2021-11-16 Macrogenics, Inc. Combination therapy for the treatment of cancer
WO2017077391A2 (en) 2015-11-04 2017-05-11 Astrazeneca Ab Dipeptidyl peptidase-4 and periostin as predictors of clinical response to eosinophil-targeted therapeutic agents in eosinophilic diseases
US11447557B2 (en) 2015-12-02 2022-09-20 Agenus Inc. Antibodies and methods of use thereof
US10836830B2 (en) 2015-12-02 2020-11-17 Agenus Inc. Antibodies and methods of use thereof
US11253590B2 (en) 2015-12-02 2022-02-22 Stsciences, Inc. Antibodies specific to glycosylated BTLA (B- and T- lymphocyte attenuator)
EP3909983A1 (en) 2015-12-02 2021-11-17 STCube & Co. Inc. Antibodies and molecules that immunospecifically bind to btn1a1 and the therapeutic uses thereof
WO2017093947A1 (en) 2015-12-04 2017-06-08 Novartis Ag Antibody cytokine engrafted compositions and methods of use for immunoregulation
US10954301B2 (en) 2015-12-14 2021-03-23 Macrogenics, Inc. Bispecific molecules having immunoreactivity with PD-1 and CTLA-4, and methods of use thereof
US11840571B2 (en) 2015-12-14 2023-12-12 Macrogenics, Inc. Methods of using bispecific molecules having immunoreactivity with PD-1 and CTLA-4
WO2017106061A1 (en) 2015-12-14 2017-06-22 Macrogenics, Inc. Bispecific molecules having immunoreactivity with pd-1 and ctla-4, and methods of use thereof
WO2017103895A1 (en) 2015-12-18 2017-06-22 Novartis Ag Antibodies targeting cd32b and methods of use thereof
WO2017122130A1 (en) 2016-01-11 2017-07-20 Novartis Ag Immune-stimulating humanized monoclonal antibodies against human interleukin-2, and fusion proteins thereof
EP3851457A1 (en) 2016-01-21 2021-07-21 Novartis AG Multispecific molecules targeting cll-1
WO2017125897A1 (en) 2016-01-21 2017-07-27 Novartis Ag Multispecific molecules targeting cll-1
EP4137570A1 (en) 2016-02-01 2023-02-22 Bioverativ Therapeutics Inc. Optimized factor viii genes
US11753461B2 (en) 2016-02-01 2023-09-12 Bioverativ Therapeutics Inc. Optimized factor VIII genes
WO2017136358A1 (en) 2016-02-01 2017-08-10 Bioverativ Therapeutics Inc. Optimized factor viii genes
WO2017142928A1 (en) 2016-02-17 2017-08-24 Macrogenics, Inc. Ror1-binding molecules, and methods of use thereof
WO2017152085A1 (en) 2016-03-04 2017-09-08 Bristol-Myers Squibb Company Combination therapy with anti-cd73 antibodies
WO2017151176A1 (en) 2016-03-04 2017-09-08 The Rockefeller University Antibodies to cd40 with enhanced agonist activity
US11851482B2 (en) 2016-04-04 2023-12-26 Genzyme Corporation Anti-complement factor Bb antibodies and uses thereof
WO2017180813A1 (en) 2016-04-15 2017-10-19 Macrogenics, Inc. Novel b7-h3 binding molecules, antibody drug conjugates thereof and methods of use thereof
US10961311B2 (en) 2016-04-15 2021-03-30 Macrogenics, Inc. B7-H3 binding molecules, antibody drug conjugates thereof and methods of use thereof
US11591400B2 (en) 2016-04-15 2023-02-28 Macrogenics, Inc. B7-H3 directed antibody drug conjugates
WO2017189724A1 (en) 2016-04-27 2017-11-02 Novartis Ag Antibodies against growth differentiation factor 15 and uses thereof
WO2017205721A1 (en) 2016-05-27 2017-11-30 Agenus Inc. Anti-tim-3 antibodies and methods of use thereof
WO2017216724A1 (en) 2016-06-15 2017-12-21 Novartis Ag Methods for treating disease using inhibitors of bone morphogenetic protein 6 (bmp6)
WO2018005954A2 (en) 2016-07-01 2018-01-04 Resolve Therapeutics, Llc Optimized binuclease fusions and methods
WO2018057735A1 (en) 2016-09-21 2018-03-29 Nextcure, Inc. Antibodies for siglec-15 and methods of use thereof
US11390675B2 (en) 2016-09-21 2022-07-19 Nextcure, Inc. Antibodies for Siglec-15 and methods of use thereof
WO2018071500A1 (en) 2016-10-11 2018-04-19 Agenus Inc. Anti-lag-3 antibodies and methods of use thereof
US10844119B2 (en) 2016-10-11 2020-11-24 Agenus Inc. Anti-LAG-3 antibodies and methods of use thereof
US10882908B2 (en) 2016-10-11 2021-01-05 Agenus Inc. Anti-LAG-3 antibodies and methods of use thereof
WO2018075758A1 (en) 2016-10-19 2018-04-26 Alexion Pharmaceuticals, Inc. A method of quantitating unbound c5 in a sample
US10415015B2 (en) 2016-10-31 2019-09-17 Iovance Biotherapeutics, Inc. Engineered artificial antigen presenting cells for tumor infiltrating lymphocyte expansion
US11667890B2 (en) 2016-10-31 2023-06-06 Iovance Biotherapeutics, Inc. Engineered artificial antigen presenting cells for tumor infiltrating lymphocyte expansion
US11359028B2 (en) 2016-11-09 2022-06-14 Agenus Inc. Anti-OX40 antibodies and anti-GITR antibodies
WO2018102743A1 (en) 2016-12-02 2018-06-07 Bioverativ Therapeutics Inc. Methods of treating hemophilic arthropathy using chimeric clotting factors
WO2018102760A1 (en) 2016-12-02 2018-06-07 Bioverativ Therapeutics Inc. Methods of inducing immune tolerance to clotting factors
WO2018106864A1 (en) 2016-12-07 2018-06-14 Agenus Inc. Antibodies and methods of use thereof
WO2018106862A1 (en) 2016-12-07 2018-06-14 Agenus Inc. Anti-ctla-4 antibodies and methods of use thereof
EP4289484A2 (en) 2016-12-07 2023-12-13 Agenus Inc. Anti-ctla-4 antibodies and methods of use thereof
WO2018116267A2 (en) 2016-12-23 2018-06-28 Novartis Ag Methods of treatment with anti-factor xi/xia antibodies
WO2018119196A1 (en) 2016-12-23 2018-06-28 Immunogen, Inc. Immunoconjugates targeting adam9 and methods of use thereof
US11242402B2 (en) 2016-12-23 2022-02-08 Macrogenics, Inc. ADAM9-binding molecules, and methods of use thereof
WO2018116255A1 (en) 2016-12-23 2018-06-28 Novartis Ag Factor xi antibodies and methods of use
WO2018128939A1 (en) 2017-01-05 2018-07-12 Gensun Biopharma Inc. Checkpoint regulator antagonists
WO2018129332A1 (en) 2017-01-06 2018-07-12 Iovance Biotherapeutics, Inc. Expansion of tumor infiltrating lymphocytes (tils) with tumor necrosis factor receptor superfamily (tnfrsf) agonists and therapeutic combinations of tils and tnfrsf agonists
WO2018129336A1 (en) 2017-01-06 2018-07-12 Iovance Biotherapeutics, Inc. Expansion of tumor infiltrating lymphocytes with potassium channel agonists and therapeutic uses thereof
WO2018146594A1 (en) 2017-02-08 2018-08-16 Novartis Ag Fgf21 mimetic antibodies and uses thereof
US11459394B2 (en) 2017-02-24 2022-10-04 Macrogenics, Inc. Bispecific binding molecules that are capable of binding CD137 and tumor antigens, and uses thereof
WO2018187613A2 (en) 2017-04-07 2018-10-11 Bristol-Myers Squibb Company Anti-icos agonist antibodies and uses thereof
WO2018191502A2 (en) 2017-04-13 2018-10-18 Agenus Inc. Anti-cd137 antibodies and methods of use thereof
WO2018193427A1 (en) 2017-04-21 2018-10-25 Staten Biotechnology B.V. Anti-apoc3 antibodies and methods of use thereof
US11643473B2 (en) 2017-04-24 2023-05-09 Alexion Pharmaceuticals, Inc. Antibody immune cell inhibitor fusion proteins
WO2018200422A1 (en) 2017-04-24 2018-11-01 Alexion Pharmaceuticals, Inc. Antibody immune cell inhibitor fusion proteins
EP4275698A2 (en) 2017-05-01 2023-11-15 Agenus Inc. Anti-tigit antibodies and methods of use thereof
WO2018204363A1 (en) 2017-05-01 2018-11-08 Agenus Inc. Anti-tigit antibodies and methods of use thereof
WO2018209115A1 (en) 2017-05-10 2018-11-15 Iovance Biotherapeutics, Inc. Expansion of tumor infiltrating lymphocytes from liquid tumors and therapeutic uses thereof
WO2018215937A1 (en) 2017-05-24 2018-11-29 Novartis Ag Interleukin-7 antibody cytokine engrafted proteins and methods of use in the treatment of cancer
WO2018215936A1 (en) 2017-05-24 2018-11-29 Novartis Ag Antibody-cytokine engrafted proteins and methods of use in the treatment of cancer
WO2018215935A1 (en) 2017-05-24 2018-11-29 Novartis Ag Antibody-cytokine engrafted proteins and methods of use for immune related disorders
WO2018215938A1 (en) 2017-05-24 2018-11-29 Novartis Ag Antibody-cytokine engrafted proteins and methods of use
WO2018218056A1 (en) 2017-05-25 2018-11-29 Birstol-Myers Squibb Company Antibodies comprising modified heavy constant regions
EP4098662A1 (en) 2017-05-25 2022-12-07 Bristol-Myers Squibb Company Antibodies comprising modified heavy constant regions
WO2018222689A1 (en) 2017-05-31 2018-12-06 Stcube & Co., Inc. Antibodies and molecules that immunospecifically bind to btn1a1 and the therapeutic uses thereof
WO2018222685A1 (en) 2017-05-31 2018-12-06 Stcube & Co., Inc. Methods of treating cancer using antibodies and molecules that immunospecifically bind to btn1a1
US11542331B2 (en) 2017-06-06 2023-01-03 Stcube & Co., Inc. Methods of treating cancer using antibodies and molecules that bind to BTN1A1 or BTN1A1-ligands
WO2018226671A1 (en) 2017-06-06 2018-12-13 Stcube & Co., Inc. Methods of treating cancer using antibodies and molecules that bind to btn1a1 or btn1a1-ligands
WO2018229715A1 (en) 2017-06-16 2018-12-20 Novartis Ag Compositions comprising anti-cd32b antibodies and methods of use thereof
US11365241B2 (en) 2017-07-27 2022-06-21 Alexion Pharmaceuticals, Inc. High concentration anti-C5 antibody formulations
WO2019032898A1 (en) 2017-08-09 2019-02-14 Bioverativ Therapeutics Inc. Nucleic acid molecules and uses thereof
WO2019040674A1 (en) 2017-08-22 2019-02-28 Sanabio, Llc Soluble interferon receptors and uses thereof
US11306144B2 (en) 2017-08-25 2022-04-19 Five Prime Therapeutics, Inc. B7-H4 antibodies and methods of use thereof
US11814431B2 (en) 2017-08-25 2023-11-14 Five Prime Therapeutics, Inc. B7-H4 antibodies and methods of use thereof
WO2019040780A1 (en) 2017-08-25 2019-02-28 Five Prime Therapeutics Inc. B7-h4 antibodies and methods of use thereof
EP3456736A1 (en) 2017-09-19 2019-03-20 Tillotts Pharma Ag Antibody variants
WO2019057567A1 (en) 2017-09-19 2019-03-28 Tillotts Pharma Ag Antibody variants
EP3456737A1 (en) 2017-09-19 2019-03-20 Tillotts Pharma Ag Antibody variants
WO2019057565A1 (en) 2017-09-19 2019-03-28 Tillotts Pharma Ag Antibody variants
WO2019081983A1 (en) 2017-10-25 2019-05-02 Novartis Ag Antibodies targeting cd32b and methods of use thereof
WO2019087115A1 (en) 2017-10-31 2019-05-09 Staten Biotechnology B.V. Anti-apoc3 antibodies and methods of use thereof
WO2019103857A1 (en) 2017-11-22 2019-05-31 Iovance Biotherapeutics, Inc. Expansion of peripheral blood lymphocytes (pbls) from peripheral blood
US11795226B2 (en) 2017-12-12 2023-10-24 Macrogenics, Inc. Bispecific CD16-binding molecules and their use in the treatment of disease
WO2019118873A2 (en) 2017-12-15 2019-06-20 Iovance Biotherapeutics, Inc. Systems and methods for determining the beneficial administration of tumor infiltrating lymphocytes, and methods of use thereof and beneficial administration of tumor infiltrating lymphocytes, and methods of use thereof
WO2019129054A1 (en) 2017-12-27 2019-07-04 信达生物制药(苏州)有限公司 Triabody, preparation method and use thereof
WO2019133747A1 (en) 2017-12-27 2019-07-04 Bristol-Myers Squibb Company Anti-cd40 antibodies and uses thereof
US11306149B2 (en) 2017-12-27 2022-04-19 Bristol-Myers Squibb Company Anti-CD40 antibodies and uses thereof
WO2019152692A1 (en) 2018-02-01 2019-08-08 Bioverativ Therapeutics, Inc. Use of lentiviral vectors expressing factor viii
WO2019160829A1 (en) 2018-02-13 2019-08-22 Iovance Biotherapeutics, Inc. Expansion of tumor infiltrating lymphocytes (tils) with adenosine a2a receptor antagonists and therapeutic combinations of tils and adenosine a2a receptor antagonists
US11685781B2 (en) 2018-02-15 2023-06-27 Macrogenics, Inc. Variant CD3-binding domains and their use in combination therapies for the treatment of disease
WO2019169229A1 (en) 2018-03-01 2019-09-06 Nextcure, Inc. Klrg1 binding compositions and methods of use thereof
US11746148B2 (en) 2018-03-27 2023-09-05 Innovent Biologics (Suzhou) Co., Ltd. Antibody molecules comprising a single-domain antigen-binding site and Fab fragments
WO2019184909A1 (en) 2018-03-27 2019-10-03 信达生物制药(苏州)有限公司 Novel antibody molecule, and preparation method and use thereof
WO2019191295A1 (en) 2018-03-28 2019-10-03 Bristol-Myers Squibb Company Interleukin-2/interleukin-2 receptor alpha fusion proteins and methods of use
WO2019222682A1 (en) 2018-05-18 2019-11-21 Bioverativ Therapeutics Inc. Methods of treating hemophilia a
WO2019229658A1 (en) 2018-05-30 2019-12-05 Novartis Ag Entpd2 antibodies, combination therapies, and methods of using the antibodies and combination therapies
WO2019229701A2 (en) 2018-06-01 2019-12-05 Novartis Ag Binding molecules against bcma and uses thereof
WO2019236417A1 (en) 2018-06-04 2019-12-12 Biogen Ma Inc. Anti-vla-4 antibodies having reduced effector function
WO2020005945A1 (en) 2018-06-26 2020-01-02 Immunogen, Inc. Immunoconjugates targeting adam9 and methods of use thereof
US10647773B2 (en) 2018-06-29 2020-05-12 Gensun Biopharma, Inc. Trispecific antagonists
US11518813B2 (en) 2018-06-29 2022-12-06 Gensun Biopharma, Inc. Trispecific antagonists
US11667716B2 (en) 2018-06-29 2023-06-06 Gensun Biopharma, Inc. Bispecific antagonist comprising a LAG-3 binding domain
US10597453B2 (en) 2018-06-29 2020-03-24 Gensun Biopharma, Inc. Antitumor immune checkpoint regulator antagonists
US11001635B2 (en) 2018-06-29 2021-05-11 Gensun Biopharma Inc. Antitumor antagonists
US11851493B2 (en) 2018-06-29 2023-12-26 Gensun Biopharma, Inc. Trispecific antagonists
WO2020010117A2 (en) 2018-07-03 2020-01-09 Bristol-Myers Squibb Company Fgf21 formulations
WO2020033863A1 (en) 2018-08-09 2020-02-13 Bioverativ Therapeutics Inc. Nucleic acid molecules and uses thereof for non-viral gene therapy
WO2020096682A2 (en) 2018-08-31 2020-05-14 Iovance Biotherapeutics, Inc. Treatment of nsclc patients refractory for anti-pd-1 antibody
WO2020070678A2 (en) 2018-10-03 2020-04-09 Staten Biotechnology B.V. Antibodies specific for human and cynomolgus apoc3 and methods of use thereof
WO2020079580A1 (en) 2018-10-15 2020-04-23 Novartis Ag Trem2 stabilizing antibodies
WO2020086665A1 (en) 2018-10-26 2020-04-30 Immunogen, Inc. Epcam antibodies, activatable antibodies, and immunoconjugates, and uses thereof
WO2020096989A1 (en) 2018-11-05 2020-05-14 Iovance Biotherapeutics, Inc. Treatment of nsclc patients refractory for anti-pd-1 antibody
WO2020112781A1 (en) 2018-11-28 2020-06-04 Bristol-Myers Squibb Company Antibodies comprising modified heavy constant regions
WO2020142740A1 (en) 2019-01-04 2020-07-09 Resolve Therapeutics, Llc Treatment of sjogren's disease with nuclease fusion proteins
WO2020176497A1 (en) 2019-02-26 2020-09-03 Rgenix, Inc. High-affinity anti-mertk antibodies and uses thereof
WO2020180733A1 (en) 2019-03-01 2020-09-10 Iovance Biotherapeutics, Inc. Expansion of tumor infiltrating lymphocytes from liquid tumors and therapeutic uses thereof
WO2020206063A1 (en) 2019-04-03 2020-10-08 Genzyme Corporation Anti-alpha beta tcr binding polypeptides with reduced fragmentation
WO2020236792A1 (en) 2019-05-21 2020-11-26 Novartis Ag Cd19 binding molecules and uses thereof
WO2020236797A1 (en) 2019-05-21 2020-11-26 Novartis Ag Variant cd58 domains and uses thereof
US11827671B2 (en) 2019-05-24 2023-11-28 Sanofi Methods for treating systemic sclerosis
WO2020242989A1 (en) 2019-05-24 2020-12-03 Sanofi Methods for treating systemic sclerosis
WO2020254197A1 (en) 2019-06-18 2020-12-24 Bayer Aktiengesellschaft Adrenomedullin-analogues for long-term stabilization and their use
WO2020263312A1 (en) 2019-06-28 2020-12-30 Gensun Biopharma, Inc. ANTITUMOR ANTAGONIST CONSISTING OF A MUTATED TGFβ1 - RII EXTRACELLULAR DOMAIN AND AN IMMUNOGLOBULIN SCAFFOLD
WO2021030488A1 (en) 2019-08-12 2021-02-18 Bienvenue David Leonard 4-1bb and ox40 binding proteins and related compositions and methods, antibodies against 4-1bb, antibodies against ox40
WO2021042019A1 (en) 2019-08-30 2021-03-04 Agenus Inc. Anti-cd96 antibodies and methods of use thereof
WO2021053560A1 (en) 2019-09-18 2021-03-25 Novartis Ag Combination therapy with entpd2 and cd73 antibodies
WO2021053559A1 (en) 2019-09-18 2021-03-25 Novartis Ag Entpd2 antibodies, combination therapies, and methods of using the antibodies and combination therapies
WO2021062323A1 (en) 2019-09-26 2021-04-01 Stcube & Co. Antibodies specific to glycosylated ctla-4 and methods of use thereof
WO2021067389A1 (en) 2019-09-30 2021-04-08 Bioverativ Therapeutics Inc. Lentiviral vector formulations
WO2021072277A1 (en) 2019-10-09 2021-04-15 Stcube & Co. Antibodies specific to glycosylated lag3 and methods of use thereof
WO2021158938A1 (en) 2020-02-06 2021-08-12 Bristol-Myers Squibb Company Il-10 and uses thereof
WO2021174034A1 (en) 2020-02-28 2021-09-02 Genzyme Corporation Modified binding polypeptides for optimized drug conjugation
US11879004B2 (en) 2020-02-28 2024-01-23 Genzyme Corporation Modified binding polypeptides for optimized drug conjugation
US11242382B2 (en) 2020-04-20 2022-02-08 Genzyme Corporation Humanized anti-complement factor Bb antibodies
WO2021216899A1 (en) * 2020-04-22 2021-10-28 Kindred Biosciences, Inc. Il4/il13 receptor molecules for veterinary use
WO2021231732A1 (en) 2020-05-15 2021-11-18 Bristol-Myers Squibb Company Antibodies to garp
WO2021233834A1 (en) 2020-05-17 2021-11-25 Astrazeneca Uk Limited Sars-cov-2 antibodies and methods of selecting and using the same
WO2022006153A1 (en) 2020-06-29 2022-01-06 Resolve Therapeutics, Llc Treatment of sjogren's syndrome with nuclease fusion proteins
WO2022010798A1 (en) 2020-07-06 2022-01-13 Kiromic BioPharma, Inc. Mesothelin isoform binding molecules and chimeric pd1 receptor molecules, cells containing the same and uses thereof
WO2022031978A1 (en) 2020-08-06 2022-02-10 Bioverativ Usa Inc. Inflammatory cytokines and fatigue in subject with a complement mediated disease
WO2022034044A1 (en) 2020-08-10 2022-02-17 Astrazeneca Uk Limited Sars-cov-2 antibodies for treatment and prevention of covid-19
WO2022076606A1 (en) 2020-10-06 2022-04-14 Iovance Biotherapeutics, Inc. Treatment of nsclc patients with tumor infiltrating lymphocyte therapies
WO2022076952A1 (en) 2020-10-06 2022-04-14 Iovance Biotherapeutics, Inc. Treatment of nsclc patients with tumor infiltrating lymphocyte therapies
US11932685B2 (en) 2020-10-23 2024-03-19 Xencor, Inc. Fc variants with altered binding to FcRn
WO2022097060A1 (en) 2020-11-06 2022-05-12 Novartis Ag Cd19 binding molecules and uses thereof
WO2022108627A1 (en) 2020-11-18 2022-05-27 Kiromic Biopharma, Inc.Kiromic Biopharma, Inc. Gamma-delta t cell manufacturing processes and chimeric pd1 receptor molecules
WO2022119976A1 (en) 2020-12-01 2022-06-09 Aptevo Research And Development Llc Heterodimeric psma and cd3-binding bispecific antibodies
WO2022125941A1 (en) 2020-12-11 2022-06-16 Iovance Biotherapeutics, Inc. Treatment of cancer patients with tumor infiltrating lymphocyte therapies in combination with braf inhibitors and/or mek inhibitors
WO2022133149A1 (en) 2020-12-17 2022-06-23 Iovance Biotherapeutics, Inc. Treatment of cancers with tumor infiltrating lymphocytes
WO2022133140A1 (en) 2020-12-17 2022-06-23 Iovance Biotherapeutics, Inc. Treatment with tumor infiltrating lymphocyte therapies in combination with ctla-4 and pd-1 inhibitors
WO2022147196A2 (en) 2020-12-31 2022-07-07 Iovance Biotherapeutics, Inc. Devices and processes for automated production of tumor infiltrating lymphocytes
WO2022165260A1 (en) 2021-01-29 2022-08-04 Iovance Biotherapeutics, Inc. Methods of making modified tumor infiltrating lymphocytes and their use in adoptive cell therapy
WO2022187741A2 (en) 2021-03-05 2022-09-09 Iovance Biotherapeutics, Inc. Tumor storage and cell culture compositions
WO2022198141A1 (en) 2021-03-19 2022-09-22 Iovance Biotherapeutics, Inc. Methods for tumor infiltrating lymphocyte (til) expansion related to cd39/cd69 selection and gene knockout in tils
WO2022204155A1 (en) 2021-03-23 2022-09-29 Iovance Biotherapeutics, Inc. Cish gene editing of tumor infiltrating lymphocytes and uses of same in immunotherapy
WO2022204564A2 (en) 2021-03-25 2022-09-29 Iovance Biotherapeutics, Inc. Methods and compositions for t-cell coculture potency assays and use with cell therapy products
WO2022212645A1 (en) 2021-03-31 2022-10-06 Bioverativ Usa Inc. Reducing surgery-associated hemolysis in cold agglutinin disease patients
WO2022225981A2 (en) 2021-04-19 2022-10-27 Iovance Biotherapeutics, Inc. Chimeric costimulatory receptors, chemokine receptors, and the use of same in cellular immunotherapies
WO2022245754A1 (en) 2021-05-17 2022-11-24 Iovance Biotherapeutics, Inc. Pd-1 gene-edited tumor infiltrating lymphocytes and uses of same in immunotherapy
WO2022256820A1 (en) 2021-06-03 2022-12-08 Gensun Biopharma Inc. Multispecific antagonists
WO2022263357A1 (en) 2021-06-14 2022-12-22 Argenx Iip Bv Anti-il-9 antibodies and methods of use thereof
WO2023004074A2 (en) 2021-07-22 2023-01-26 Iovance Biotherapeutics, Inc. Method for cryopreservation of solid tumor fragments
WO2023010060A2 (en) 2021-07-27 2023-02-02 Novab, Inc. Engineered vlrb antibodies with immune effector functions
WO2023009716A1 (en) 2021-07-28 2023-02-02 Iovance Biotherapeutics, Inc. Treatment of cancer patients with tumor infiltrating lymphocyte therapies in combination with kras inhibitors
WO2023031615A1 (en) 2021-09-02 2023-03-09 Djs Antibodies Ltd Polypeptides
WO2023039488A1 (en) 2021-09-09 2023-03-16 Iovance Biotherapeutics, Inc. Processes for generating til products using pd-1 talen knockdown
WO2023049862A1 (en) 2021-09-24 2023-03-30 Iovance Biotherapeutics, Inc. Expansion processes and agents for tumor infiltrating lymphocytes
WO2023056362A1 (en) 2021-09-30 2023-04-06 Seagen Inc. B7-h4 antibody-drug conjugates for the treatment of cancer
WO2023077015A2 (en) 2021-10-27 2023-05-04 Iovance Biotherapeutics, Inc. Systems and methods for coordinating manufacturing of cells for patient-specific immunotherapy
WO2023079086A1 (en) 2021-11-05 2023-05-11 Astrazeneca Uk Limited Composition for treatment and prevention of covid-19
WO2023086803A1 (en) 2021-11-10 2023-05-19 Iovance Biotherapeutics, Inc. Methods of expansion treatment utilizing cd8 tumor infiltrating lymphocytes
WO2023091968A1 (en) 2021-11-17 2023-05-25 Disc Medicine, Inc. Methods for treating anemia of kidney disease
WO2023147486A1 (en) 2022-01-28 2023-08-03 Iovance Biotherapeutics, Inc. Tumor infiltrating lymphocytes engineered to express payloads
WO2023147488A1 (en) 2022-01-28 2023-08-03 Iovance Biotherapeutics, Inc. Cytokine associated tumor infiltrating lymphocytes compositions and methods
WO2023196877A1 (en) 2022-04-06 2023-10-12 Iovance Biotherapeutics, Inc. Treatment of nsclc patients with tumor infiltrating lymphocyte therapies
WO2023201369A1 (en) 2022-04-15 2023-10-19 Iovance Biotherapeutics, Inc. Til expansion processes using specific cytokine combinations and/or akti treatment
WO2023209568A1 (en) 2022-04-26 2023-11-02 Novartis Ag Multispecific antibodies targeting il-13 and il-18
WO2023209177A1 (en) 2022-04-29 2023-11-02 Astrazeneca Uk Limited Sars-cov-2 antibodies and methods of using the same
WO2023220608A1 (en) 2022-05-10 2023-11-16 Iovance Biotherapeutics, Inc. Treatment of cancer patients with tumor infiltrating lymphocyte therapies in combination with an il-15r agonist
WO2023240109A1 (en) 2022-06-07 2023-12-14 Regeneron Pharmaceuticals, Inc. Multispecific molecules for modulating t-cell activity, and uses thereof
WO2023240124A1 (en) 2022-06-07 2023-12-14 Regeneron Pharmaceuticals, Inc. Pseudotyped viral particles for targeting tcr-expressing cells
WO2023242362A1 (en) 2022-06-15 2023-12-21 argenx BV Fcrn/antigen-binding molecules and methods of use
WO2023242372A1 (en) 2022-06-15 2023-12-21 argenx BV Fcrn/hsa binding molecules and methods of use
WO2023245048A1 (en) 2022-06-15 2023-12-21 Bioverativ Usa Inc. Anti-complement c1s antibody formulation
WO2023250507A1 (en) 2022-06-24 2023-12-28 Bioverativ Usa Inc. Methods for treating complement-mediated diseases
WO2024011114A1 (en) 2022-07-06 2024-01-11 Iovance Biotherapeutics, Inc. Devices and processes for automated production of tumor infiltrating lymphocytes
WO2024015830A1 (en) 2022-07-12 2024-01-18 Cytomx Therapeutics, Inc. Epcam immunoconjugates and uses thereof
WO2024026474A1 (en) 2022-07-29 2024-02-01 Regeneron Pharmaceuticals, Inc. Compositions and methods for transferrin receptor (tfr)-mediated delivery to the brain and muscle
WO2024026494A1 (en) 2022-07-29 2024-02-01 Regeneron Pharmaceuticals, Inc. Viral particles retargeted to transferrin receptor 1
WO2024026470A2 (en) 2022-07-29 2024-02-01 Regeneron Pharmaceuticals, Inc. Anti-tfr:payload fusions and methods of use thereof
WO2024030758A1 (en) 2022-08-01 2024-02-08 Iovance Biotherapeutics, Inc. Chimeric costimulatory receptors, chemokine receptors, and the use of same in cellular immunotherapies
US11773160B1 (en) 2022-08-05 2023-10-03 Anaveon AG Immune-stimulating IL-2 fusion proteins
WO2024050524A1 (en) 2022-09-01 2024-03-07 University Of Georgia Research Foundation, Inc. Compositions and methods for directing apolipoprotein l1 to induce mammalian cell death

Similar Documents

Publication Publication Date Title
WO1998023289A1 (en) MODULATION OF IgG BINDING TO FcRn
ES2240981T3 (en) NAME CITOCINE LERK-7.
Adams et al. Highly specific in vivo tumor targeting by monovalent and divalent forms of 741F8 anti-c-erb B-2 single-chain Fv
US20160000868A1 (en) Receptor-targeting reagents
KR102165464B1 (en) Antibody specific for cd22 and methods of use thereof
PT1240337E (en) Methods and compositions for prolonging elimination half-times of bioactive compounds
JPH07504883A (en) Materials containing ribosome-inactivating proteins and methods of preparing and using them
CN112094349B (en) Antibody targeting interleukin 36R and preparation method and application thereof
AU722722B2 (en) Concurrent in-vivo immunoconjugate binding to multiple epitopes of vascular permeability factor on tumor-associated blood vessels
CN105026432A (en) Aprotinin-derived polypeptide-antibody conjugates
US20130259806A1 (en) Dimeric molecular complexes with free cysteine residues and conjugates thereof
US5952471A (en) Antibody that binds to cluster w-4 polypeptide of human small cell lung carcinoma cells
Friden et al. Characterization, receptor mapping and blood-brain barrier transcytosis of antibodies to the human transferrin receptor.
KR100425627B1 (en) Method of use related to the treatment of protein and tumor extracted from liver of mammal
AU8742991A (en) Antagonists of human gamma interferon
CN113045659B (en) anti-CD73 humanized antibodies
US6416734B1 (en) Recombinant alpha-fetoprotein for treating and diagnosing cancers
JP5544626B2 (en) Interstitial pneumonia treatment
CN112794911B (en) Humanized anti-folate receptor 1 antibody and application thereof
WO1994025483A1 (en) Immunotherapeutic peptides derived from toxic shock syndrome toxin-1, antibodies thereto, their uses in pharmaceutical compositions and diagnosis
WO2023025304A1 (en) Polypeptide fusion molecule close to natural molecule
JP3268147B2 (en) Monoclonal antibody
US20230053131A1 (en) Antibodies to canine interleukin-4 receptor alpha
CN117659203A (en) anti-MET/EGFR bispecific antibody and drug conjugate thereof
CN116925220A (en) IL20RB neutralizing antibody and medical application thereof

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): CA JP

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH DE DK ES FI FR GB GR IE IT LU MC NL PT SE

121 Ep: the epo has been informed by wipo that ep was designated in this application
NENP Non-entry into the national phase

Ref country code: JP

Ref document number: 1998524782

Format of ref document f/p: F

122 Ep: pct application non-entry in european phase