Patent ID: 11857599
Assignee: ACCELERON PHARMA INC.
Field: Pharmaceuticals (Chemistry)
Classification: CPC A  C | IPC A  C

Claim 0:
1. A method of treating spinal muscular atrophy (SMA) in a patient in need thereof, comprising administering to the patient an effective amount of a recombinant ALK4:ActRIIB heteromultimer comprising at least one ALK4-Fc fusion protein and at least one ActRIIB-Fc fusion protein, wherein
(A) the at least one ALK4-Fc fusion protein comprises an ALK4 polypeptide and an IgG1 Fc domain polypeptide, wherein the ALK4 polypeptide comprises an amino acid sequence selected from
(i) an amino acid sequence at least 90% identical to amino acid residues 34-101 of SEQ ID NO: 9; and
(ii) an amino acid sequence at least 90% identical to SEQ ID NO: 10; and

(B) the at least one ActRIIB-Fc fusion protein comprises an ActRIIB polypeptide and an IgG1 Fc domain polypeptide, wherein the ActRIIB polypeptide comprises an amino acid sequence selected from
(i) an amino acid sequence at least 90% identical to amino acid residues 29-109 of SEQ ID NO: 1;
(ii) an amino acid sequence at least 90% identical to SEQ ID NO: 2;
(iii) an amino acid sequence least sequence 90% identical to SEQ ID NO: 3;
(iv) an amino acid sequence as set forth in SEQ ID NO: 5;
(v) an amino acid as set forth in SEQ ID NO: 6;

wherein the Fc domain polypeptide of
(a) one of the ALK4-Fc and the ActRIIB-Fc fusion proteins has an amino acid sequence of SEQ ID NO: 23 and the other has an amino acid sequence of SEQ ID NO: 24;
(b) one of the ALK4-Fc and the ActRIIB-Fc fusion proteins has an amino acid sequence of SEQ ID NO: 25 and the other has an amino acid sequence of SEQ ID NO: 26;
(c) one of the ALK4-Fc and the ActRIIB-Fc fusion proteins has an amino acid sequence of SEQ ID NO: 27 and the other has an amino acid sequence of SEQ ID NO: 28;

wherein the Fc domain polypeptide of one of the ALK4-Fc and the ActRIIB-Fc fusion proteins is optionally substituted at position H213 by an arginine (H213R); or
(d) one of the ALK4-Fc and the ActRIIB-Fc fusion proteins has an amino acid sequence of SEQ ID NO: 66 and the other has an amino acid sequence of SEQ ID NO: 67;

wherein in (a)-(d), the Fc domain polypeptide may optionally be provided with the lysine (K) residue removed from the C-terminus.