BMP-7 variants with improved properties
AssigneeXencor, Inc.
InventorsJohn R. Desjarlais, Shannon Alicia Marshall, Jonathan Zalevsky
Life of this patent
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Abstract
The invention relates to variants of BMP-7 with improved properties and methods for their use.
Claims2
A non-naturally occurring variant BMP-7 protein comprising amino acid D at position Vb(120) of the sequence:
- Fx(1-20)-Vb(21)-Fx(22-38)-Vb(39)-Fx(40-64)-Vb(65)-Fx(66-71)-Vb(72)-Fx(73-77)-Vb(78)-Fx(79-92)-Vb(93)-Fx(94-119)-Vb(120)-Fx(121-134)-Vb(135) whereinFx(1-20) corresponds to amino acid residues 1-20 of human BMP-7 (SEQ ID NO:5);
- Vb(21) is selected from the group consisting of L and G;
- Fx(22-38) corresponds to amino acid residues 22-38 of human BMP-7 (SEQ ID NO:5);
- Vb(39) is selected from the group consisting of K, A and S;
- Fx(40-64) corresponds to amino acid residues 40-64 of human BMP-7 (SEQ ID NO:5);
- Vb(65) is selected from the group consisting of Y and N;
- Fx(66-71) corresponds to amino acid residues 66-71 of human BMP-7 (SEQ ID NO:5);
- Vb(72) is selected from the group consisting of A and D;
- Fx(73-77) corresponds to amino acid residues 73-77 of human BMP-7 (SEQ ID NO:5);
- Vb(78) is selected from the group consisting of Y and H;
- Fx(79-92) corresponds to amino acid residues 79-92 of human BMP-7 (SEQ ID NO:5);
- Vb(93) is selected from the group consisting of F, H, S and T;
- Fx(94-119) corresponds to amino acid residues 94-119 of human BMP-7 (SEQ ID NO:5);
- Fx(121-134) corresponds to amino acid residues 121-134 of human BMP-7 (SEQ ID NO:5);
- Vb(135) is selected from the group consisting of A and E;
- wherein said variant comprises an amino acid substitution as compared to human BMP-7 (SEQ ID NO:5), wherein said variant retains at least 50% bioactivity relative to human BMP-7 (SEQ ID NO:5), as determined by differentiation of C2C12 cells as measured by alkaline phosphatase activity, and, wherein said variant BMP-7 protein differs from human BMP-7 (SEQ ID NO:5) by 1, 2, 3, 4 or 5 residues.
A variant BMP-7 protein comprising the substitution S210D as compared to human BMP-7 (SEQ ID NO:5), wherein said variant retains at least 50% bioactivity relative to human BMP-7 (SEQ ID NO:5), as determined by differentiation of C2C12 cells as measured by alkaline phosphatase activity, and wherein said variant BMP-7 protein differs from human BMP-7 (SEQ ID NO:5) by 1, 2, 3, 4 or 5 residues.
Dependencies are inferred from the claim text.