Modified and stabilized GDF propeptides and uses thereof
First Claim
1. An isolated BMP-11 propeptide comprising an amino acid sequence that is at least 90% identical to SEQ ID NO:
- 11 and has a mutation corresponding to the aspartate residue at position 98 of SEQ ID NO;
11.
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Accused Products
Abstract
Modified and stabilized propeptides of Growth Differentiation Factor proteins, such as GDF-8 and Bone Morphogenetic Protein-11, are disclosed. Also disclosed are methods for making and using the modified propeptides to prevent or treat human or animal disorders in which an increase in muscle tissue would be therapeutically beneficial. Such disorders include muscle or neuromuscular disorders (such as amyotrophic lateral sclerosis, muscular dystrophy, muscle atrophy, congestive obstructive pulmonary disease, muscle wasting syndrome, sarcopenia, or cachexia), metabolic diseases or disorders (such as such as type 2 diabetes, noninsulin-dependent diabetes mellitus, hyperglycemia, or obesity), adipose tissue disorders (such as obesity), and bone degenerative diseases (such as osteoporosis).
67 Citations
32 Claims
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1. An isolated BMP-11 propeptide comprising an amino acid sequence that is at least 90% identical to SEQ ID NO:
- 11 and has a mutation corresponding to the aspartate residue at position 98 of SEQ ID NO;
11. - View Dependent Claims (4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19)
- 11 and has a mutation corresponding to the aspartate residue at position 98 of SEQ ID NO;
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2. An isolated BMP-11 propeptide comprising an amino acid sequence that is at least 85% identical to SEQ ID NO:
- 11, wherein the BMP-11 propeptide has a mutation corresponding to the aspartate residue at position 98 of SEQ ID NO;
11.
- 11, wherein the BMP-11 propeptide has a mutation corresponding to the aspartate residue at position 98 of SEQ ID NO;
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3. A BMP-11 propeptide comprising an amino acid sequence that is at least 95% identical to SEQ ID NO:
- 11 and has a mutation at the aspartate residue corresponding to position 98 of SEQ ID NO;
11.
- 11 and has a mutation at the aspartate residue corresponding to position 98 of SEQ ID NO;
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20. A BMP-11 propeptide comprising a non-human mammalian BMP-11 propeptide homolog of SEQ ID NO:
- 11, wherein the propeptide has a mutation that modifies an aspartate residue corresponding to position 98 of SEQ ID NO;
11.
- 11, wherein the propeptide has a mutation that modifies an aspartate residue corresponding to position 98 of SEQ ID NO;
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21. A method of treating a patient suffering from a muscular or neuromuscular disease or disorder comprising:
administering a therapeutically effective amount of a BMP-11 propeptide that has a mutation that modifies the aspartate residue corresponding to aspartate 98 of SEQ ID NO;
11 and a pharmaceutically acceptable excipient to said patient, wherein the BMP-11 propeptide comprises an amino acid sequence that is at least 85% identical to SEQ ID NO;
11 and has a mutation that modifies the aspartate residue corresponding to position 98 of SEQ ID NO;
11, thereby treating a patient suffering from the muscular or neuromuscular disease or disorder.- View Dependent Claims (22, 23, 24, 25, 26, 27, 28)
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29. A method of treating a patient suffering from a metabolic disorder or disease resulting from abnormal glucose homeostasis, comprising administering a therapeutically effective amount of a BMP-11 propeptide that has a mutation that modifies the aspartate residue corresponding to aspartate 98 of SEQ ID NO:
- 11 and a pharmaceutically acceptable excipient to said patient, wherein the BMP-11 propeptide comprises an amino acid sequence that is at least 85% identical to SEQ ID NO;
11 and has a mutation that modifies the aspartate residue corresponding to position 98 of SEQ ID NO;
11, thereby treating the metabolic disease or disorder. - View Dependent Claims (30)
- 11 and a pharmaceutically acceptable excipient to said patient, wherein the BMP-11 propeptide comprises an amino acid sequence that is at least 85% identical to SEQ ID NO;
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31. A method of treating a patient suffering from a bone degenerative disorder, comprising administering a therapeutically effective amount of a BMP-11 propeptide that has a mutation that modifies the aspartate residue corresponding to aspartate 98 of SEQ ID NO:
- 11 and a pharmaceutically acceptable excipient to said patient, wherein the BMP-11 propeptide comprises an amino acid sequence that is at least 85% identical to SEQ ID NO;
11 and has a mutation that modifies the aspartate residue corresponding to position 98 of SEQ ID NO;
11, thereby treating the bone degenerative disorder. - View Dependent Claims (32)
- 11 and a pharmaceutically acceptable excipient to said patient, wherein the BMP-11 propeptide comprises an amino acid sequence that is at least 85% identical to SEQ ID NO;
Specification