Modified TGF-β superfamily protein
View Patent ↗The invention provides modified TGF-β family proteins having altered biological or biochemical properties, and methods for making them. Specific modified protein constructs include TGF-β family member proteins that have N-terminal truncations, “latent” proteins, fusion proteins and heterodimers.
1. A pharmaceutical composition comprising a therapeutically effective amount of an N-terminally truncated OP-1 or an N-terminally truncated mutant OP-1, wherein said N-terminally truncated OP-1 or N-terminally truncated mutant OP-1 is selected from the group consisting of:
a) a polypeptide consisting of amino acid residues 323-431 of SEQ ID NO: 39;
b) a polypeptide consisting essentially of amino acid residues 21-129 of SEQ ID NO: 89; and
c) a polypeptide consisting essentially of the amino acid sequence of SEQ ID NO: 69.
2. The pharmaceutical composition of claim 1 , wherein the N-terminally truncated mutant OP-1 is a polypeptide consisting essentially of the amino acid sequence of SEQ ID NO: 69.
3. The pharmaceutical composition of claim 1 , wherein the composition is a liquid solution or a liquid suspension.
4. The pharmaceutical composition of claim 3 , wherein the composition is an aqueous solution.
5. The pharmaceutical composition of claim 1 , further comprising a biocompatible matrix.
6. The pharmaceutical composition of claim 5 , wherein the biocompatible carrier is selected from the group consisting of hyaluronic acid, tricalcium phosphate, polybutyrate, polylactide, polyglycolide, lactide/glycolide copolymers, collagen, hydroxyapatite, ceramics and carboxymethylcellulose.
7. A method of regenerating bone in a patient, comprising the step of administering to the patient the pharmaceutical composition of any one of claims 1 to 6 .
8. A method of regenerating a non-mineralized skeletal or connective tissue in a patient, comprising the step of administering to the patient the pharmaceutical composition of any one of claims 1 to 6 .
9. The method of claim 8 , wherein the non-mineralized skeletal or connective tissue is cartilage.
10. The method of claim 8 , wherein the non-mineralized skeletal or connective tissue is selected from the group consisting of fibrocartilage, ligament, tendon, joint capsule, menisci, synovial membrane tissue, muscle and fascia.
11. The method of claim 8 , wherein the non-mineralized skeletal or connective tissue is articular cartilage.
12. The method of claim 8 , wherein the non-mineralized skeletal or connective tissue is an intervertebral disk.
13. The method of claim 7 , wherein the pharmaceutical composition is administered locally.
14. The method of claim 8 , wherein the pharmaceutical composition is administered locally.