Abstract: The present invention provides methods of treating, ameliorating, or inhibiting tumor growth, cancer, or pathological angiogenesis by administering to a subject in need thereof a human antibody or fragment thereof that specifically binds to human delta-like ligand 4 (hDll4) and blocks hDll4 binding to a Notch receptor. The anti-hDll4 antibody or fragment thereof of the present invention have a high affinity with the KD of 500 pM or less, as measured by surface plasmon resonance.

Abstract: Non-human animal cells and non-human animals comprising a humanized Asgr1 locus and methods of using such non-human animal cells and non-human animals are provided. Non-human animal cells or non-human animals comprising a humanized Asgr1 locus express a human ASGR1 protein or an Asgr1 protein, fragments of which are from human ASGR1. Methods are provided for using such non-human animals comprising a humanized Asgr1 locus to assess in vivo efficacy of human-ASGR1-mediated delivery of therapeutic molecules or therapeutic complexes to the liver and to assess the efficacy of therapeutic molecules or therapeutic complexes acting via human-ASGR1-mediated mechanisms.

Abstract: An human antibody or antigen-binding fragment of a human antibody that specifically binds and inhibits human proprotein convertase subtilisin/kexin type 9 (hPCSK9) characterized by the ability to reduce serum LDL cholesterol by 40-80% over a 24, 60 or 90 day period relative to predose levels, with little or no reduction in serum HDL cholesterol and/or with little or no measurable effect on liver function, as determined by ALT and AST measurements.

Abstract: Non-human animal cells and non-human animals comprising a humanized Asgr1 locus and methods of using such non-human animal cells and non-human animals are provided. Non-human animal cells or non-human animals comprising a humanized Asgr1 locus express a human ASGR1 protein or an Asgr1 protein, fragments of which are from human ASGR1. Methods are provided for using such non-human animals comprising a humanized Asgr1 locus to assess in vivo efficacy of human-ASGR1-mediated delivery of therapeutic molecules or therapeutic complexes to the liver and to assess the efficacy of therapeutic molecules or therapeutic complexes acting via human-ASGR1-mediated mechanisms.

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 antibodies that bind to the class Ill variant of EGFR (EGFRvIII) and methods of using the same. According to certain embodiments, the antibodies of the invention bind human EGFRvIII with high affinity. The antibodies of the invention may be fully human antibodies. The invention includes anti-EGFRvIII 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.

Abstract: Methods are disclosed for treating osteoarthritis in a human subject in need thereof, comprising administering to the subject a therapeutically effective amount of an anti-human NGF antibody, or antigen-binding fragment thereof, wherein at least one symptom associated with osteoarthritis is prevented, ameliorated or improved.

Abstract: Genetically modified non-human animals are provided that express an immunoglobulin variable domain that comprises at least one histidine, wherein the at least one histidine is encoded by a substitution of a non-histidine codon in the germline of the animal with a histidine codon, or the insertion of a histidine codon in a germline immunoglobulin nucleic acid sequence. Immunoglobulin genes comprising histidines in one or more CDRs, in an N-terminal region, and/or in a loop 4 region are also provided. Immunoglobulin variable domains comprising one or more histidines (e.g., histidine clusters) substituted for non-antigen-binding non-histidine residues. Non-human animals that are progeny of animals comprising modified heavy chain variable loci (V, D, J segments), modified light chain variable loci (V, J segments), and rearranged germline light chain genes (VJ sequences) are also provided. Non-human animals that make immunoglobulin domains that bind antigens in a pH-sensitive manner are provided.

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 treating, ameliorating, or inhibiting tumor growth, cancer, or pathological angiogenesis by administering to a subject in need thereof a human antibody or fragment thereof that specifically binds to human delta-like ligand 4 (hDll4) and blocks hDll4 binding to a Notch receptor. The anti-hDll4 antibody or fragment thereof of the present invention have a high affinity with the KD of 500 pM or less, as measured by surface plasmon resonance.

Abstract: Genetically modified non-human animals are provided that express an immunoglobulin variable domain that comprises at least one histidine, wherein the at least one histidine is encoded by a substitution of a non-histidine codon in the germline of the animal with a histidine codon, or the insertion of a histidine codon in a germline immunoglobulin nucleic acid sequence. Immunoglobulin genes comprising histidines in one or more CDRs, in an N-terminal region, and/or in a loop 4 region are also provided. Immunoglobulin variable domains comprising one or more histidines (e.g., histidine clusters) substituted for non-antigen-binding non-histidine residues. Non-human animals that are progeny of animals comprising modified heavy chain variable loci (V, D, J segments), modified light chain variable loci (V, J segments), and rearranged germline light chain genes (VJ sequences) are also provided. Non-human animals that make immunoglobulin domains that bind antigens in a pH-sensitive manner are provided.

Abstract: An human antibody or antigen-binding fragment of a human antibody that specifically binds and inhibits human proprotein convertase subtilisin/kexin type 9 (hPCSK9) characterized by the ability to reduce serum LDL cholesterol by 40-80% over a 24, 60 or 90 day period relative to predose levels, with little or no reduction in serum HDL cholesterol and/or with little or no measurable effect on liver function, as determined by ALT and AST measurements.

Abstract: The present invention provides nucleic acid molecules that encode antibodies or antigen-binding fragments thereof, which specifically bind human interleukin-4 receptor (lL-4R). Also provided are expression vectors comprising nucleic acid molecule that encode anti-lL-4R antibodies, host cells comprising the expression vectors, and methods of producing anti-lL-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 the class Ill variant of EGFR (EGFRvIII) and methods of using the same. According to certain embodiments, the antibodies of the invention bind human EGFRvIII with high affinity. The antibodies of the invention may be fully human antibodies. The invention includes anti-EGFRvIII 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.

Abstract: An human antibody or antigen-binding fragment of a human antibody that specifically binds and inhibits human proprotein convertase subtilisin/kexin type 9 (hPCSK9) characterized by the ability to reduce serum LDL cholesterol by 40-80% over a 24, 60 or 90 day period relative to predose levels, with little or no reduction in serum HDL cholesterol and/or with little or no measurable effect on liver function, as determined by ALT and AST measurements.

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: Methods are disclosed for treating osteoarthritis in a human subject in need thereof, comprising administering to the subject a therapeutically effective amount of an anti-human NGF antibody, or antigen-binding fragment thereof, wherein at least one symptom associated with osteoarthritis is prevented, ameliorated or improved.

Abstract: Methods are disclosed for treating osteoarthritis in a human subject in need thereof, comprising administering to the subject a therapeutically effective amount of an anti-human NGF antibody, or antigen-binding fragment thereof, wherein at least one symptom associated with osteoarthritis is prevented, ameliorated or improved.

Abstract: The present invention provides antibodies that bind to the class III variant of EGFR (EGFRvIII) and methods of using the same. According to certain embodiments, the antibodies of the invention bind human EGFRvIII with high affinity. The antibodies of the invention may be fully human antibodies. The invention includes anti-EGFRvIII 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.

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.