An isolated protein comprising a variant activin IIB receptor (vActRIIB) polypeptide wherein the polypeptide is selected from the group consisting of:n(a) a polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 18, wherein the polypeptide comprises an amino acid substitution at position 28, wherein the substitution at position 28 is A, W, Y, F, Q, V, I, L, M, K, or H for E;(b) a polypeptide comprising the amino acid sequence set forth in amino acids 19 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 A, W, Y, F, Q, V, I, L, M, K, or H for E;(c) a polypeptide comprising the amino acid sequence set forth in amino acids 23 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 A, W, Y, F, Q, V, I, L, M, K, or H for E;(d) a polypeptide comprising the amino acid sequence set forth in 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 A, W, Y, F, Q, V, I, L, M, K, or H for E; and(e) a polypeptide having at least 95% identity to any one of (a) through (d), wherein the polypeptide comprises an amino acid substitution at the position corresponding to position 28 of SEQ ID NO:18, wherein the substitution at position 28 is A, W, Y, F, Q, V, I, L, M, K, or H for E, and wherein the polypeptide is capable of binding myostatin, activin A, or GDF-11.
›2.↳ 1The protein of claim 1, wherein the substitution at position 28 of the vActRIIB polypeptide is selected from the group of amino acids consisting of A,…d2
The protein of claim 1, wherein the substitution at position 28 of the vActRIIB polypeptide is selected from the group of amino acids consisting of A, W and Y for E.
›3.↳ 1The protein of claim 1, wherein the substitution at position 28 of the vActRIIB polypeptide is W for E.d2
The protein of claim 1, wherein the substitution at position 28 of the vActRIIB polypeptide is W for E.
›4.↳ 1The protein of claim 1, wherein the isolated protein further comprises the sequence set forth in SEQ ID NO:79.d2
The protein of claim 1, wherein the isolated protein further comprises the sequence set forth in SEQ ID NO:79.
›5.↳ 1The pharmaceutical composition of claim 1, wherein the isolated protein further comprises the sequence set forth in SEQ ID NO:80.d2
The pharmaceutical composition of claim 1, wherein the isolated protein further comprises the sequence set forth in SEQ ID NO:80.
›6.↳ 1The protein of claim 1, wherein the polypeptide sequence has at least 95% identity to the amino acid sequence set forth at amino acids 25 through 134 …d2
The protein of claim 1, wherein the polypeptide sequence has at least 95% identity to the amino acid sequence set forth at amino acids 25 through 134 of SEQ ID NO: 18, and wherein the polypeptide comprises an amino acid substitution at position 28, wherein the substitution at position 28 is A, W, Y, F, Q, V, I, L, M, K, or H for E, and wherein the polypeptide is capable of binding myostatin, activin A, or GDF-11.
›7.↳ 1The protein of claim 1, wherein the polypeptide sequence has at least 95% identity to the amino acid sequence set forth at amino acids 25 through 134 …d2
The protein of claim 1, wherein the polypeptide sequence has at least 95% 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 W for E, and wherein the isolated protein further comprises an Fc domain linked to vActRIIB polypeptide via a linker.
›8.↳ 1The protein of claim 1, wherein the polypeptide sequence has at least 99% identity to the amino acid sequence set forth at amino acids 25 through 134 …d2+3
The protein of claim 1, wherein the polypeptide sequence has 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 W for E, and wherein the isolated protein further comprises a human Fc domain (SEQ ID NO:80) linked to vActRIIB polypeptide via a peptide linker (SEQ ID NO:79).
›9.↳ 8A homodimer comprising the protein of claim 8.d3+1
A homodimer comprising the protein of claim 8.
›10.↳ 9A pharmaceutical composition comprising the homodimer of claim 9 and an excipient.d4
A pharmaceutical composition comprising the homodimer of claim 9 and an excipient.
›11.↳ 8A pharmaceutical composition comprising the protein of claim 8 and an excipient.d3
A pharmaceutical composition comprising the protein of claim 8 and an excipient.
›12.↳ 1The isolated protein of claim 1, wherein the polypeptide is fused to at least one heterologous polypeptide.d2
The isolated protein of claim 1, wherein the polypeptide is fused to at least one heterologous polypeptide.
›13.↳ 1A dimer comprising the protein of claim 1.d2+3
A dimer comprising the protein of claim 1.
›14.↳ 13The dimer of claim 13, wherein the dimer is a homodimer.d3+1
The dimer of claim 13, wherein the dimer is a homodimer.
›15.↳ 14A pharmaceutical composition comprising the dimer of claim 14 and an excipient.d4
A pharmaceutical composition comprising the dimer of claim 14 and an excipient.
›16.↳ 13A pharmaceutical composition comprising the dimer of claim 13 and an excipient.d3
A pharmaceutical composition comprising the dimer of claim 13 and an excipient.
›17.↳ 1A pharmaceutical composition comprising the protein of claim 1 and an excipient.d2
A pharmaceutical composition comprising the protein of claim 1 and an excipient.
›18.↳ 1The protein of claim 1, wherein the polypeptide sequence has at least 97% identity to the amino acid sequence set forth at amino acids 25 through 134 …d2
The protein of claim 1, wherein the polypeptide sequence has at least 97% identity to the amino acid sequence set forth at amino acids 25 through 134 of SEQ ID NO: 18, and wherein the polypeptide comprises an amino acid substitution at position 28, wherein the substitution at position 28 is A, W, Y, F, Q, V, I, L, M, K, or H for E, and wherein the polypeptide is capable of binding myostatin, activin A, or GDF-11.
›19.↳ 1The protein of claim 1, wherein the polypeptide sequence has at least 98% identity to the amino acid sequence set forth at amino acids 25 through 134 …d2
The protein of claim 1, wherein the polypeptide sequence has at least 98% identity to the amino acid sequence set forth at amino acids 25 through 134 of SEQ ID NO: 18, and wherein the polypeptide comprises an amino acid substitution at position 28, wherein the substitution at position 28 is A, W, Y, F, Q, V, I, L, M, K, or H for E, and wherein the polypeptide is capable of binding myostatin, activin A, or GDF-11.
›20.↳ 1The protein of claim 1, wherein the polypeptide sequence has at least 99% identity to the amino acid sequence set forth at amino acids 25 through 134 …d2
The protein of claim 1, wherein the polypeptide sequence has at least 99% identity to the amino acid sequence set forth at amino acids 25 through 134 of SEQ ID NO: 18, and wherein the polypeptide comprises an amino acid substitution at position 28, wherein the substitution at position 28 is A, W, Y, F, Q, V, I, L, M, K, or H for E, and wherein the polypeptide is capable of binding myostatin, activin A, or GDF-11v.
