Truncated aggrecanase molecules
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Abstract
Truncated aggrecanase proteins and nucleotides sequences encoding them as well as processes for producing them are disclosed. Additionally, aggrecanases with amino acid mutations that lead to increased stability and expression levels in comparison with wild-type or native aggrecanases are also disclosed. Aggrecanases of the invention are especially useful for development of compositions for treatment of diseases such as osteoarthritis. Methods for developing inhibitors of the aggrecanase enzymes and antibodies to the enzymes for treatment of conditions characterized by the degradation of aggrecan are also disclosed.
23 Citations
50 Claims
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1-30. -30. (canceled)
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31. An isolated, recombinantly-produced or chemically-synthesized aggrecanase, said aggrecanase being a truncated version of the amino acid sequence of SEQ ID NO:
- 2, said truncated version comprising a truncation of at least 10 amino acid residues from the C-terminus of said amino acid sequence, wherein said at least 10 amino acid residues are located C-terminal to a disintegrin domain of said amino acid sequence.
- View Dependent Claims (32, 33, 34, 35, 36, 49)
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37. An isolated, recombinantly-produced or chemically-synthesized aggrecanase, said aggrecanase being a mutated version of the amino acid sequence of SEQ ID NO:
- 2, said mutated version comprising a deletion of at least 10 amino acid residues C-terminal to a disintegrin domain of the amino acid sequence of SEQ ID NO;
2, wherein, when aligned, the amino acid sequence of SEQ ID NO;
2 and the amino acid sequence of the mutated version are at least 70% identical. - View Dependent Claims (38, 39, 40, 41, 42, 43, 50)
- 2, said mutated version comprising a deletion of at least 10 amino acid residues C-terminal to a disintegrin domain of the amino acid sequence of SEQ ID NO;
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44. An isolated, recombinantly-produced or chemically-synthesized fusion protein consisting of:
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an amino acid sequence selected from the group consisting of SEQ ID NOs;
4, 6, 8, and 10;
at least one peptide tag; and
at least one peptide linker connecting the amino acid sequence to the at least one peptide tag. - View Dependent Claims (45, 46, 47, 48)
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Specification