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US 9,284,364 B2Granted
Isolated nucleic acid molecule encoding a fusion protein comprising an activin receptor
AssigneeAmgen Inc.
InventorsHuiquan Han, Keith Soo-Nyung Kwak, Xiaolan Zhou
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Abstract
The present invention provides novel activin IIB5 receptor polypeptides 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 receptor polypeptides. Compositions and methods for treating muscle-wasting, metabolic and other disorders are also provided.
Claims20
An isolated nucleic acid molecule comprising a first polynucleotide encoding at least one heterologous protein and a second polynucleotide selected from the group consisting of:
- (a) a polynucleotide comprising a polynucleotide sequence at least 95% identical to the polynucleotide sequence set forth in SEQ ID NO:
- 1;
- (b) a polynucleotide encoding a polypeptide comprising an amino acid sequence at least 95% identical to the amino acid sequence set forth in SEQ ID NO:
- 2, with or without a signal sequence, wherein the polypeptide is capable of binding myostatin, activin A, or GDF-11;
- and
- (c) a polynucleotide that hybridizes to (a) or (b) or the complete complement of (a) or (b) in the presence of 50% formamide, 6× sodium chloride/sodium citrate (SSC) at 42° C. and washing conditions of 60° C., 0.5×SSC, 0.1% sodium dodecyl sulfate (SDS), and
- wherein the protein encoded by the isolated nucleic acid molecule comprises at least one of the following characteristics:
- (1) the protein has activin A neutralizing activity IC50 (nM) vs. 20 nM activin that is less than the activin A neutralizing activity IC50 (nM) vs. 20 nM activin of a control protein comprising amino acids 1-124 of the sequence set forth in SEQ ID NO:5 linked to human IgG1 Fc;
- or (2) the protein has myostatin-neutralizing activity IC50 (nM) vs. 4 nM myostatin that is less than the myostatin-neutralizing activity IC50 (nM) vs. 4 nM myostatin of the control protein.
6 more elements
Dependencies are inferred from the claim text.