Abstract: The present invention provides antibodies that bind to prolactin receptor (PRLR) and methods of using the same. According to certain embodiments, the antibodies of the invention bind human PRLR with high affinity. In certain embodiments, the invention includes antibodies that bind PRLR and block prolactin-mediated cell signaling. In other embodiments, the invention includes antibodies that bind PRLR but do not block prolactin-mediated cell signaling. The antibodies of the invention may be fully human antibodies. The invention includes anti-PRLR antibodies conjugated to a cytotoxic agent, radionuclide, or other moiety detrimental to cell growth or proliferation. The antibodies of the invention are useful for the treatment of various cancers as well as other PRLR-related disorders.

Abstract: The present invention provides antibodies that bind to prolactin receptor (PRLR) and methods of using the same. According to certain embodiments, the antibodies of the invention bind human PRLR with high affinity. In certain embodiments, the invention includes antibodies that bind PRLR and block prolactin-mediated cell signaling. In other embodiments, the invention includes antibodies that bind PRLR but do not block prolactin-mediated cell signaling. According to certain embodiments, the invention includes antibodies that bind to the first fibronectin-like type III domain of the extracellular domain of PRLR. The antibodies of the invention may be fully human antibodies. The invention includes anti-PRLR antibodies conjugated to a cytotoxic agent, radionuclide, or other moiety detrimental to cell growth or proliferation. The antibodies of the invention are useful for the treatment of various cancers as well as other PRLR-related disorders.

Abstract: A fusion polypeptide comprising (A)x-M-(A?)y, wherein A and A? are each polypeptides capable of binding a target receptor. The fusion polypeptides of the invention form multimeric proteins which activate the target receptor. A and A? may be each be an antibody or fragment derived from an antibody specific for a target receptor, such as the same or different scFv fragments, and/or a ligand or ligand fragment or derivative capable of binding the target protein, M is a multimerizing component, and X and Y are independently a number between 1-10.

Abstract: A fusion polypeptide comprising (A)x-M-(A?)y, wherein A and A? are each polypeptides capable of binding a target receptor. The fusion polypeptides of the invention form multimeric proteins which activate the target receptor. A and A? may be each be an antibody or fragment derived from an antibody specific for a target receptor, such as the same or different scFv fragments, and/or a ligand or ligand fragment or derivative capable of binding the target protein, M is a multimerizing component, and X and Y are independently a number between 1-10.

Abstract: The present invention provides antibodies that bind to interleukin-33 (IL-33) and methods of using the same. The invention includes antibodies that inhibit or attenuate IL-33-mediated signaling. The antibodies of the invention may function to block the interaction between IL-33 and ST2. Alternatively, certain antibodies of the invention inhibit or attenuate IL-33-mediated signaling without blocking the IL-33/ST2 interaction. According to certain embodiments of the invention, the antibodies are fully human antibodies that bind to human IL-33 with high affinity. The antibodies of the invention are useful for the treatment of diseases and disorders associated with IL-33 signaling and/or IL-33 cellular expression, such as inflammatory diseases, or allergic diseases.

Abstract: The present invention provides nucleic acid molecules that encode antibodies or antigen-binding fragments thereof, which specifically bind human interleukin-4 receptor (IL-4R).

Abstract: The present invention provides interleukin-33 (IL-33) antagonists comprising one or more IL-33-binding domains and one or more multimerizing domains and methods of using the same. According to certain embodiments of the invention, the IL-33-binding domains can comprise an IL-33-binding portion of an ST2 protein and/or an extracellular portion of an IL-1 RAcP protein. The IL-33 antagonists of the invention are useful for the treatment of diseases and disorders associated with IL-33 signaling and/or IL-33 cellular expression, such as infectious diseases, inflammatory diseases, allergic diseases and fibrotic diseases.

Abstract: A human antibody or an antigen-binding fragment which binds human IL-6 receptor (hIL-6R) with a KD of about 500 pM or less and blocks IL-6 activity with an IC50 of 200 pM or less, is provided. In preferred embodiments, the antibody the antibody or antigen-binding fragment binds hIL-6R with an affinity at least 2-fold higher relative to its binding monkey IL-6R.

Abstract: The present invention provides methods of preventing or treating rheumatoid arthritis using a fully human antibody or antigen-binding fragment thereof that specifically binds human interleukin-6 receptor (hIL-6R). The methods of the present invention may include administration of a second therapeutic agent, such as one or more of a non-steroidal anti-inflammatory drug (NSAID), a glucocorticoid, a disease-modifying anti-rheumatic drug (DMARD), or a TNF-alpha antagonist, T-cell blocker, anti-CD20 antibody, an IL-1, JAK or IL-17 antagonist, or any combination thereof.

Abstract: The present invention provides VEGF antagonists with improved pharmacokinetic properties. According to certain embodiments, a fusion polypeptide capable of antagonizing VEGF activity is provided comprising a modified extracellular ligand binding domain of a VEGF receptor fused to a multimerizing component.

Abstract: The present invention provides nucleic acid molecules that encode antibodies or antigen-binding fragments thereof, which specifically bind human interleukin-4 receptor (IL-4R). Also provided are expression vectors comprising nucleic acid molecule that encode anti-IL-4R antibodies, host cells comprising the expression vectors, and methods of producing anti-IL-4R antibodies or antigen-binding fragments thereof comprising growing the host cells under conditions permitting production of the antibody or fragment, and recovering the antibody or fragment so produced.

Abstract: The present invention provides antibodies that bind to CD3 and methods of using the same. According to certain embodiments, the antibodies of the invention bind human CD3 with high affinity and induce human T cell proliferation. The invention includes antibodies that bind CD3 and induce T cell-mediated killing of tumor cells. According to certain embodiments, the present invention provides bispecific antigen-binding molecules comprising a first antigen-binding domain that specifically binds human CD3, and a second antigen-binding molecule that specifically binds human CD20. In certain embodiments, the bispecific antigen-binding molecules of the present invention are capable of inhibiting the growth of B-cell tumors expressing CD20. The antibodies and bispecific antigen-binding molecules of the invention are useful for the treatment of diseases and disorders in which an upregulated or induced targeted immune response is desired and/or therapeutically beneficial.

Abstract: The present invention provides antibodies and antigen-binding fragments thereof that specifically bind proprotein convertase subtilisin/kexin-9 (PCSK9) with greater affinity at neutral pH than at acidic pH. The antibodies of the invention may possess one or more amino acid changes as compared to antibodies that do not exhibit pH-dependent binding properties. For example, the present invention includes anti-PCSK9 antibodies which possess one or more histidine substitutions in one or more complementarity determining regions. The antibodies of the invention, with pH-dependent binding properties, remain in circulation and exhibit cholesterol lowering activity for prolonged periods of time in animal subjects as compared to anti-PCSK9 antibodies that do not exhibit pH-dependent binding properties.

Abstract: The present invention provides methods for producing a fusion protein capable of binding vascular endothelial cell growth factor (VEGF). The methods of the invention comprise growing recombinant cells in suspension culture, wherein the recombinant cells contain an expression vector comprising a nucleic acid molecule encoding a fusion protein that binds VEGF, and isolating the fusion protein from the suspension culture. The fusion protein may comprise a VEGF receptor component having an immunoglobulin-like (Ig) domain 2 of a first VEGF receptor, an Ig domain 3 of a second VEGF receptor, and a multimerizing component.

Abstract: The present invention provides antibodies that bind to EGFR and methods of using same. According to certain embodiments of the invention, the antibodies are fully human antibodies that bind to human EGFR with high affinity. In certain embodiments, the antibodies of the present invention are capable of inhibiting the growth of tumor cells expressing high levels of EGFR and/or inducing antibody-dependent cell-mediated cytotoxicity (ADCC) of such cells. The antibodies of the invention are useful for the treatment of various cancers as well as other EGFR-related disorders.

Abstract: A fusion polypeptide comprising (A)x-M-(A?)y, wherein A and A? are each polypeptides capable of binding a target receptor. The fusion polypeptides of the invention form multimeric proteins which activate the target receptor. A and A? may be each be an antibody or fragment derived from an antibody specific for a target receptor, such as the same or different scFv fragments, and/or a ligand or ligand fragment or derivative capable of binding the target protein, M is a multimerizing component, and X and Y are independently a number between 1-10.

Abstract: The present invention provides methods of preventing or treating rheumatoid arthritis using a fully human antibody or antigen-binding fragment thereof that specifically binds human interleukin-6 receptor (hIL-6R). The methods of the present invention may include administration of a second therapeutic agent, such as one or more of a non-steroidal anti-inflammatory drug (NSAID), a glucocorticoid, a disease-modifying anti-rheumatic drug (DMARD), or a TNF-alpha antagonist, T-cell blocker, anti-CD20 antibody, an IL-1, JAK or IL-17 antagonist, or any combination thereof.

Abstract: A fusion polypeptide comprising (A)x-M-(A?)y, wherein A and A? are each polypeptides capable of binding a target receptor. The fusion polypeptides of the invention form multimeric proteins which activate the target receptor. A and A? may be each be an antibody or fragment derived from an antibody specific for a target receptor, such as the same or different scFv fragments, and/or a ligand or ligand fragment or derivative capable of binding the target protein, M is a multimerizing component, and X and Y are independently a number between 1-10.

Abstract: The present invention provides multispecific antigen-binding molecules and uses thereof. The multispecific antigen-binding molecules comprise a first antigen-binding domain that specifically binds a target molecule, and a second antigen-binding domain that specifically binds an internalizing effector protein. The multispecific antigen-binding molecules of the present invention can, in some embodiments, be bispecific antibodies that are capable of binding both a target molecule and an internalizing effector protein. In certain embodiments of the invention, the simultaneous binding of the target molecule and the internalizing effector protein by the multispecific antigen-binding molecule of the present invention results in the attenuation of the activity of the target molecule to a greater extent than the binding of the target molecule alone.

Abstract: A fusion polypeptide comprising (A)x-M-(A?)y, wherein A and A? are each polypeptides capable of binding a target receptor. The fusion polypeptides of the invention form multimeric proteins which activate the target receptor. A and A? may be each be an antibody or fragment derived from an antibody specific for a target receptor, such as the same or different scFv fragments, and/or a ligand or ligand fragment or derivative capable of binding the target protein, M is a multimerizing component, and X and Y are independently a number between 1-10.