Variant activin receptor polypeptides, alone or in combination with chemotherapy, and uses thereof
AssigneeAmgen Inc.
InventorsJeonghoon Sun, Lei-Ting Tony Tam, Huiquan Han, Keith Soo-Nyung Kwak, Xiaolan Zhou
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Abstract
The present invention provides variant activin IIB soluble receptor polypeptides and proteins capable of binding and inhibiting the activities of activin A, myostatin, or GDF-11. The present invention also provides polynucleotides, vectors and host cells capable of producing the variant polypeptides and proteins. Compositions and methods for treating muscle-wasting and other diseases and disorders are also provided.
Claims21
1-53. (canceled)
A pharmaceutical composition comprising i) an isolated protein comprising a variant activin IIB receptor polypeptide (vActRIIB) wherein vActRIIB comprises a polypeptide sequence having at least 99% identity to the amino acid sequence set forth at amino acids 25 through 134 of SEQ ID NO:
- 18, wherein the polypeptide comprises an amino acid substitution at position 28, and wherein the polypeptide is capable of binding myostatin, activin A, or GDF-11, and ii) a chemotherapeutic agent.
A method of reducing the size of a gonadal tumor mass in a subject in need of such treatment comprising administering to the subject:
- an effective amount of an isolated protein comprising a variant activin IIB receptor polypeptide (vActRIIB) wherein vActRIIB comprises a polypeptide sequence having at least 99% identity to the amino acid sequence set forth at amino acids 25 through 134 of SEQ ID NO:
- 18, wherein the polypeptide comprises an amino acid substitution at position 28, wherein the substitution at position 28 is selected from the group of amino acids consisting of A, W, and Y for E, and wherein the polypeptide is capable of binding myostatin, activin A, or GDF-11;
- and a chemotherapeutic agent.
A method of treating a gonadal cancer in a subject in need of such treatment comprising administering to the subject:
- an effective amount of an isolated protein comprising a variant activin IIB receptor polypeptide (vActRIIB) wherein vActRIIB comprises a polypeptide sequence having at least 99% identity to the amino acid sequence set forth at amino acids 25 through 134 of SEQ ID NO:
- 18, wherein the polypeptide comprises an amino acid substitution at position 28, wherein the substitution at position 28 is selected from the group of amino acids consisting of A, W, and Y for E, and wherein the polypeptide is capable of binding myostatin, activin A, or GDF-11;
- and a chemotherapeutic agent.
Dependencies are inferred from the claim text.