| US 7,612,040 B2 | ||
| Lefty polypeptides and derivatives thereof | ||
| John Knopf, Carlisle, Mass. (US); Jasbir Seehra, Lexington, Mass. (US); and Ravindra Kumar, Shrewsbury, Mass. (US) | ||
| Assigned to Acceleron Pharma Inc., Cambridge, Mass. (US) | ||
| Filed on Jun. 30, 2006, as Appl. No. 11/479,181. | ||
| Claims priority of provisional application 60/696226, filed on Jul. 01, 2005. | ||
| Prior Publication US 2007/0042958 A1, Feb. 22, 2007 | ||
| Int. Cl. A61K 38/16 (2006.01); A61K 38/18 (2006.01); A61K 38/19 (2006.01); C07K 14/00 (2006.01); C07K 14/475 (2006.01); C07K 14/51 (2006.01) | ||
| U.S. Cl. 514—12 [514/2; 530/350] | 33 Claims |
| 1. A recombinant Lefty derivative polypeptide comprising an amino acid sequence as set forth in the formula: W-A-X-B-Y,
wherein A consists essentially of an amino acid sequence at least 85% identical to the sequence of Region 2 of SEQ ID NO:
1;
wherein B consists essentially of an amino acid sequence at least 85% identical to the sequence of Region 4 of SEQ ID NO:
1;
wherein X consists of zero, one or more than one amino acid;
wherein W consists of zero, one or more than one amino acid;
wherein Y consists of zero, one or more than one amino acid;
wherein the recombinant Lefty derivative polypeptide binds to one or more of Nodal, myostatin and GDF-11;
wherein the recombinant Lefty derivative polypeptide is not a wild-type Lefty polypeptide;
wherein the recombinant Lefty derivative polypeptide comprises an amino acid sequence that is at least 95% identical to a
human Lefty polypeptide sequence selected from the group consisting of amino acids 78-353 of SEQ ID NO: 1 and amino acids
78-353 of SEQ ID NO:2; and
wherein the recombinant Lefty derivative polypeptide comprises one or more mutations within the RXXR cleavage sequence corresponding
to amino acid residues 132-135 of SEQ ID NO: 1 or 2 so as to prevent cleavage at the mutated sequence.
|