Antibody inhibitors of GDF-8 and uses thereof
AssigneeWyeth
InventorsNeil M. Wolfman, Denise O'Hara, Monique V. Davies, Geertruida M. Veldman, Kristie Grove Bridges, Lisa-Anne Whittemore
Life of this patent
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Abstract
The disclosure provides novel antibodies against growth and differentiation factor-8 (GDF-8), including antibody fragments, which inhibit GDF-8 activity in vitro and in vivo. The disclosure also provides methods for diagnosing, preventing, or treating degenerative disorders of muscle, bone, or insulin metabolism.
Claims35
An isolated antibody that specifically binds to amino acids 1–50 of the polypeptide of SEQ ID NO:15, wherein the antibody reduces GDF-8 activity associated with negative regulation of muscle mass.
An isolated antibody that specifically binds to the polypeptide of SEQ ID NO:5, wherein the antibody reduces GDF-8 activity associated with negative regulation of muscle mass.
An isolated monoclonal antibody that specifically binds to amino acids 1–50 of the polypeptide of SEQ ID NO:15, wherein the antibody has the same specificity as an antibody produced by a cell having ATCC Deposit Designation Number PTA-4236.
An antibody produced by the cell having ATCC Deposit Designation Number PTA-4236.
An isolated antibody that specifically binds to the polypeptide of SEQ ID NO:2, wherein the antibody reduces GDF-8 activity associated with negative regulation of muscle mass.
An isolated antibody that specifically binds to the polypeptide of SEQ ID NO:5, wherein the antibody reduces GDF-8 activity associated with negative regulation of muscle mass.
An isolated antibody having the same amino acid sequence as an antibody produced by a cell having ATCC Deposit Designation Number PTA-4236.
An isolated antibody that specifically binds to the polypeptide of SEQ ID NO:2, wherein the antibody comprises at least one single chain CDR chosen from amino acids 30–35 of the polypeptide of SEQ ID NO:1, amino acids 50–66 of the polypeptide of SEQ ID NO:1, and amino acids 99–102 of the polypeptide of SEQ ID NO:1.
An isolated antibody that specifically binds to the polypeptide of SEQ ID NO. 10, wherein the antibody binds to a mature GDF-8 protein with greater affinity than to a mature BMP-11 protein and reduces GDF-8 activity associated with negative regulation of muscle mass.
An antibody comprising a heavy chain variable region that comprises an amino acid sequence, wherein the amino acid sequence is SEQ ID NO:1, and wherein the antibody specifically binds to a mature GDF-8 protein and reduces one or more biological activities associated with the GDF-8 protein, relative to a GDF-8 protein that is not bound by the same antibody.
An isolated antibody that specifically binds to the polypeptide of SEQ ID NO:8, wherein the antibody comprises at least one single chain CDR chosen from amino acids 30–35 of the polypeptide of SEQ ID NO:1, amino acids 50–66 of polypeptide of SEQ ID NO:1, and amino acids 99–102 of the polypeptide of SEQ ID NO:1, and wherein the antibody reduces GDF-8 activity associated with negative regulation of muscle mass.
An antibody comprising a heavy chain variable region that comprises an amino acid sequence at least 95% identical to SEQ ID NO:1, wherein the antibody comprises CDRs of the amino acids 30–35 of the polypeptide of SEQ ID NO:1, amino acids 50–66 of the polypeptide of SEQ ID NO:1, and amino acids 99–102 of the polypeptide of SEQ ID NO:1, and wherein the antibody reduces GDF-8 activity associated with negative regulation of muscle mass.
Dependencies are inferred from the claim text.