Multifunctional protease inhibitors and their use in treatment of disease
First Claim
1. A protein conjugate comprising a) a first polypeptide comprising amino acids from about 1 to about 394 of SEQ ID NO:
- 2; and
b) a second polypeptide comprising amino acids from about 1 to 127 of SEQ ID NO;
6, wherein the first polypeptide is covalently linked to the second polypeptide through a disulfide bond between amino acid 127 of SEQ ID NO;
6 and a free cysteine residue of the SEQ ID NO;
2.
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Abstract
Fusion proteins of protease inhibitors are provided, in particular fusion proteins of alpha 1-antitrypsin (AAT) and a second protease inhibitor, such as secretory leukocyte protease inhibitor (SLPI) or tissue inhibitor of metalloproteases (TIMP). Polynucleotides encoding the fusion proteins, vectors comprising such polynucleotides, and host cells containing such vectors are also provided. Methods of making the fusion proteins of the invention are also provide, as well as methods of using the fusion proteins, for example to inhibit protease activity in a biological sample or in the treatment of an individual suffering from, or at risk for, a disease or disorder involving unwanted protease activity.
39 Citations
19 Claims
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1. A protein conjugate comprising a) a first polypeptide comprising amino acids from about 1 to about 394 of SEQ ID NO:
- 2; and
b) a second polypeptide comprising amino acids from about 1 to 127 of SEQ ID NO;
6, wherein the first polypeptide is covalently linked to the second polypeptide through a disulfide bond between amino acid 127 of SEQ ID NO;
6 and a free cysteine residue of the SEQ ID NO;
2. - View Dependent Claims (4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14)
- 2; and
- 2. A fusion protein comprising SEQ ID NO:
-
3. A fusion protein comprising SEQ ID NO:
- 20.
Specification