Bone morphogenetic agents

• US 4,795,804 A
• Filed: 08/07/1985
• Issued: 01/03/1989
• Est. Priority Date: 08/16/1983
• Status: Expired due to Fees

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Urist, Marshall R.
• Primary Examiner(s): Foelak, Morton
• Assistant Examiner(s): Nutter, Nathan M.
• Application Number:
  US06/763,479
• Time in Patent Office: 1,245 Days
• Field of Search: 530/350, 530/417, 530/356, 530/355, 530/840, 424/95
• US Class Current: 530/350
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/51 Bone morphogenetic factor; Osteogenins; Osteogenic factor; Bone-inducing factor
• CPC Class Codes: Y10S 530/84 Bones; tendons; teeth; cartilage

Abstract

The production and isolation of bone morphogenetic peptide agents displaying the osteoinductive and immunoreactive activity of bone morphogenetic protein (BMP) and deriving from natural, synthetic or recombinant DNA sources, and said agents.

Claims

1. A bone morphogenetic peptide having an amino acid sequence, said sequence selected from the group consisting of amino acid sequences of peptide fragments (BMP-p) having a relative molecular weight (M_r) of about 4K to about 7K and derived from proteolysis of bone morphogenetic protein (BMP), said peptide fragments being osteoinductive and immunoreactive with anti-BMP antibody.

2. A bone morphogenetic peptide of claim 1, wherein the BMP is human BMP.

3. A bone morphogenetic peptide of claim 2, wherein the relative molecular weight (M_r) is about 4.7K±

0.3K.

4. A bone morphogenetic peptide of claims 1, 2 or 3 wherein the amino acid sequence contains the following amino acid sequence:

-ILE - PRO - GLN - GLN - ARG - ARG - TRP - ARG - ALA - LYS - VAL - GLN - ASN - ARG - ILE-.

5. A bone morphogenentic peptide of claim 4, further including the following amino acid sequence:

-ARG - ASP - SER - TYR - LYS - PRO - VAL - HIS - GLU - LEU - ASN-.

6. A bone morphogenetic peptide of claim 5, further including the following amino acid sequence:

-ARG - CYS - ALA - ASP - GLY - TYR - ARG - LEU - CYS-.

7. A bone morphogenetic peptide of claim 1, wherein the BMP is bovine BMP.

8. A bone morphogenetic peptide of claim 7, wherein the relative molecular weight (M_r) is about 4.1K.

9. A bone morphogenetic peptide of claim 1, 2 or 3, wherein the limited proteolysis is pepsin limited proteolysis.

10. A bone morphogenetic peptide of claim 4, wherein the limited proteolysis is pepsin limited proteolysis.

11. A bone morphogenetic peptide of claim 1, 2 or 7, wherein the limited proteolysis is trypsin limited proteolysis.

12. A composition for inducing bone formation comprising a bone morphogenetic peptide selected from the group of bone morphogenetic peptides of claims 1, 2, 3, 7 or 8.

13. A composition for inducing bone formation comprising a bone morphogenetic peptide selected from the group of bone morphogenetic peptides of claim 4.

14. A composition for inducing bone formation comprising a bone morphogenetic peptide selected from the group of bone morphogenetic peptides of claims 9.

15. A composition for inducing bone formation comprising a bone morphogenetic peptide selected from the group of bone morphogenetic peptides of claims 10.

16. A composition for inducing bone formation comprising a bone morphogenetic peptide selected from the group of bone morphogenetic peptides of claims 11.

17. A method for inducing bone formation in vertebrates which comprises administering to said vertebrate in a pharmaceutically acceptable manner an effective amount of a composition according to claim 12.

18. A method for inducing bone formation in vertebrates which comprises adminstering to said vertebrate in a pharmaceutically acceptable manner an effective amount of a composition according to claim 13.

19. A method for inducing bone formation in vertebrates which comprises administering to said vertebrate in a pharmaceutically acceptable manner an effective amount of a composition according to claim 14.

20. A method for inducing bone formation in vertebrates which comprises administering to said vertebrate in a pharmaceutically acceptable manner an effective amount of a composition according to claim 15.

21. A method for inducing bone formation in vertebraes which comprises administering to said vertebrate in a pharamceutically acceptable manner an effective amount of a composition according to claim 16.