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US 7,741,284 B2Granted
BMP10 propeptides and related methods
AssigneeAcceleron Pharma Inc.
InventorsJasbir Seehra, John Knopf
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Abstract
In certain aspects, the present invention provides BMP10 propeptides for use in treating a variety of disorders including heart disorders and other disorders associated with unwanted activity of the mature BMP10 polypeptide. The present invention also provides methods of screening compounds that modulate activity of BMP10.
Claims16
A pharmaceutical preparation comprising:
- a) a polypeptide comprising a variant BMP10 propeptide;
- and
- b) a pharmaceutically acceptable carrier,
- wherein the variant BMP10 propeptide comprises a sequence alteration that decreases proteolytic cleavage of the variant relative to the naturally occurring BMP10 propeptide and has an amino acid sequence at least 98% identical to the amino acid sequence of SEQ ID NO:
- 1, and wherein said variant BMP10 propeptide has one or more of the following characteristics:
- i) binds to mature BMP10 with a Kd of at least 10−5 M;
- and
- ii) inhibits BMP10 signaling in a cell.
5 more elements
A BMP10 propeptide fusion protein comprising:
- a variant BMP10 propeptide and a second portion;
- wherein the variant BMP10 propeptide comprises a sequence alteration that decreases proteolytic cleavage of the variant relative to the naturally occurring BMP10 propeptide and has an amino acid sequence at least 98% identical to the amino acid sequence of SEQ ID NO:
- 1, and wherein said variant BMP10 propeptide has one or more of the following characteristics:
- i) binds to mature BMP10 with a Kd of at least 10−5 M;
- and
- ii) inhibits BMPI 0 signaling in a cell.
3 more elements
Dependencies are inferred from the claim text.