Abstract: The present invention is directed to therapeutic methods using IL-6 antagonists such as an Ab1 antibody or antibody fragment having binding specificity for IL-6 to prevent or treat disease or to improve survivability or quality of life of a patient in need thereof. In preferred embodiments these patients will comprise those exhibiting (or at risk of developing) an elevated serum C-reactive protein level, reduced serum albumin level, elevated D-dimer or other coagulation cascade related protein(s), cachexia, fever, weakness and/or fatigue prior to treatment. The subject therapies also may include the administration of other actives such as chemotherapeutics, anti-coagulants, statins, and others.

Abstract: This invention pertains to NGF antagonists including antibodies and antibody fragments thereof having binding specificity to human Nerve Growth Factor (“NGF”), and methods of treating pain. Methods of treating pain or eliciting an analgesic effect in an individual comprising administering an effective amount of an NGF antagonist inhibits the association of NGF with TrkA without inhibiting the association of NGF with p75. The methods may further comprise administering an effective amount of a second anti-human NGF antibody or fragment thereof which inhibits the association of NGF with p75, that may further also inhibit the association of NGF with TrkA.

Abstract: Antibodies and antibody fragments thereof with binding specificity to human Nerve Growth Factor (NGF) and methods of use for treating pain. Methods of treating pain or eliciting an analgesic effect comprising administering an effective amount of an anti-human NGF antibody or antibody fragment thereof, which inhibits the association of NGF with TrkA, and/or p75. These methods may optionally further comprising administering an effective amount of a second anti-human NGF antibody or fragment thereof (e.g., one which inhibits the association of NGF with p75, or one that inhibits the association of NGF with TrkA.

Abstract: The present invention is directed to antibodies and fragments thereof (especially chimeric and humanized) having binding specificity for HGF and their use in therapy and diagnosis. These antibodies inhibit or block HGF-associated activities including HGF's effects on cell proliferation, invasion, angiogenesis, metastasis and fibrosis. Particularly the antibodies may be used as a monotherapy or in combination therapies in treating cancer, other proliferative disorders and other conditions wherein inhibition of HGF and/or the HGF/HGF-R (c-met) interaction is desired.

Abstract: The present invention is directed to antibodies and fragments thereof having binding specificity for TNF-?. Another embodiment of this invention relates to the antibodies described herein, and binding fragments thereof, comprising the sequences of the VH, VL and CDR polypeptides described herein, and the polynucleotides encoding them. The invention also contemplates conjugates of anti-TNF-? antibodies and binding fragments thereof conjugated to one or more functional or detectable moieties. The invention also contemplates methods of making said anti-TNF-? antibodies and binding fragments thereof. Embodiments of the invention also pertain to the use of anti-TNF-? antibodies, and binding fragments thereof, for the diagnosis, assessment and treatment of diseases and disorders associated with TNF-?.

Abstract: The present invention is directed to therapeutic methods using IL-6 antagonists such as antibodies and fragments thereof having binding specificity for IL-6 to prevent or treat thrombosis in diseases associated with abnormal blood coagulation or fibrinolysis. In preferred embodiments these patients will comprise those exhibiting elevated D-dimer or other cogulation cascade related proteins and optionally will further exhibit elevated C reactive protein prior to treatment. The subject therapies also may include the administration of other actives such as chemotherapeutics, anti-coagulants, statins, et al.

Abstract: The present invention is directed to therapeutic methods using IL-6 antagonists such as anti-IL-6 antibodies and fragments thereof having binding specificity for IL-6 to prevent or treat mucositis (e.g., oral mucositis) including persons on a treatment regimen with a drug or chemotherapy and/or radiation for cancer (e.g., head and neck cancer) that is associated with increased risk of mucositis, including oral mucositis.

Abstract: The present invention is directed to therapeutic methods and compositions, especially subcutaneous and intravenous composition using antibodies and fragments thereof having binding specificity for IL-6 to prevent or treat cachexia, fever, weakness and/or fatigue in a patient in need thereof. In preferred embodiments, the anti-IL-6 antibodies will be humanized and/or will be aglycosylated. Also, in preferred embodiments these patients will comprise those exhibiting (or at risk of developing) an elevated serum C-reactive protein level. In another preferred embodiment, the patient's survivability or quality of life will preferably be improved.

Abstract: The present invention is directed to therapeutic methods using IL-6 antagonists such as anti-IL-6 antibodies and fragments thereof having binding specificity for IL-6 to prevent or treat rheumatoid arthritis.

Abstract: NGF antagonists including antibodies and antibody fragments thereof having binding specificity to human Nerve Growth Factor (“NGF”), and methods of treating pain. Methods of treating pain or eliciting an analgesic effect in an individual comprising administering an effective amount of an NGF antagonist inhibits the association of NGF with TrkA without inhibiting the association of NGF with p75. The methods may further comprise administering an effective amount of a second anti-human NGF antibody or fragment thereof which inhibits the association of NGF with p75, that may further also inhibit the association of NGF with TrkA.

Abstract: The invention relates to the use of anti-IL-6 antibodies or antibody fragments containing a specific epitopic specificity to treat conditions involving elevated Il-6. In some embodiments the anti-IL-6 antibodies contain specific CDRs.

Abstract: Processes for producing and purifying recombinant proteins are disclosed. In particular, the present disclosure provides processes of producing and purifying multi-subunit proteins expressed in yeast or filamentous fungal cells. The production and/or purification of such proteins are monitored for impurities, preferably using lectin binding assays, such that one or more process parameters may be adjusted to maximize the amount of desired recombinant protein and minimize the amount of glycosylated impurities. The processes can also be monitored for other undesired product-associated impurities, such as aggregates and nucleic acids. In exemplary embodiments, the recombinant proteins are multi-subunit proteins, such as antibodies, the host cell is a yeast, such as Pichia pastoris, and the glycosylated impurity is a glycovariant of the desired recombinant polypeptide, such as an N-linked and/or O-linked glycovariant.

Abstract: Methods of identifying antigen-specific antibody-secreting and antibody-forming cells, such as antigen-specific B cells, and methods for cloning the antigen-specific antibody sequences of the antibody produced by these cells are provided. In particular, the methods include enriching B cells for antigen-specific B cells, culturing the antigen-specific B cells to generate clonal B cell populations, detecting clonal B cells that produce a single antigen-specific antibody, optionally screening the clonal B cell populations for functional activity, staining and sorting the cells to isolate the antigen-specific B cells, sequencing the nucleic acids encoding the antigen-specific antibody sequences, expressing the sequences to produce an antibody, isolating the antibody and screening the antibody for antigen recognition. The methods provide improved enrichment and selection of antigen-specific antibody-secreting and antibody-forming cells, which enhances recovery of antigen-specific antibodies.

Abstract: Methods for producing heterologous proteins are disclosed. In particular, the present disclosure provides improved methods of producing desired proteins, including multi-subunit proteins such as antibodies, with a higher yield and improved purity. In exemplary embodiments, the transformed cells are a yeast, e.g., methylotrophic yeast such as Pichia pastoris.

Abstract: The present invention is directed to antibodies and fragments thereof having binding specificity for HGF. Another embodiment of this invention relates to the antibodies described herein, and binding fragments thereof, comprising the sequences of the VH, VL and CDR polypeptides described herein, and the polynucleotides encoding them. The invention also contemplates conjugates of anti-HGF antibodies and binding fragments thereof conjugated to one or more functional or detectable moieties. The invention also contemplates methods of making said anti-HGF antibodies and binding fragments thereof. Embodiments of the invention also pertain to the use of anti-HGF antibodies, and binding fragments thereof, for the diagnosis, assessment and treatment of diseases and disorders associated with HGF.

Abstract: The present invention is directed to antibodies and fragments thereof (especially chimeric and humanized) having binding specificity for HGF and their use in therapy and diagnosis. These antibodies inhibit or block HGF-associated activities including HGF's effects on cell proliferation, invasion, angiogenesis, metastasis and fibrosis. Particularly the antibodies may be used as a monotherapy or in combination therapies in treating cancer, other proliferative disorders and other conditions wherein inhibition of HGF and/or the HGF/HGF-R (c-met) interaction is desired.

Abstract: Novel promoters which are derived from P. pastoris pastoris which are inducible or repressible under specific growth conditions are provided. These promoters are useful for regulating the expression of a desired structural gene, e.g., a mammalian polypeptide. Particularly preferred is the use of these novel promoters to regulate gene expression in polyploidal yeast such as diploidal P. pastoris produced by mating or spheroplast fusion.

Abstract: Antibodies and antibody fragments thereof with binding specificity to human Nerve Growth Factor (NGF) and methods of use for treating pain. Methods of treating pain or eliciting an analgesic effect comprising administering an effective amount of an anti-human NGF antibody or antibody fragment thereof, which inhibits the association of NGF with TrkA, and/or p75. These methods may optionally further comprising administering an effective amount of a second anti-human NGF antibody or fragment thereof (e.g., one which inhibits the association of NGF with p75, or one that inhibits the association of NGF with TrkA.

Abstract: The present invention is directed to therapeutic methods using IL-6 antagonists such as antibodies and fragments thereof having binding specificity for IL-6 to improve survivability or quality of life of a patient in need thereof. In preferred embodiments these patients will comprise those exhibiting (or at risk of developing) an elevated serum C-reactive protein level or a reduced serum albumin level prior to treatment. In another preferred embodiment, the patient's Glasgow Prognostic Score will be increased and survivability will preferably be improved.

Abstract: The present invention is directed to therapeutic methods using IL-6 antagonists such as an Ab1 antibody or antibody fragment having binding specificity for IL-6 to prevent or treat disease or to improve survivability or quality of life of a patient in need thereof. In preferred embodiments these patients will comprise those exhibiting (or at risk of developing) an elevated serum C-reactive protein level, reduced serum albumin level, elevated D-dimer or other coagulation cascade related protein(s), cachexia, fever, weakness and/or fatigue prior to treatment. The subject therapies also may include the administration of other actives such as chemotherapeutics, anti-coagulants, statins, and others.