BMP products

• US 6,150,328 A
• Filed: 06/14/1991
• Issued: 11/21/2000
• Est. Priority Date: 07/01/1986
• Status: Expired due to Term

• Current Assignee: Genetics Institute LLC (Pfizer Inc.)
• Original Assignee: Genetics Institute LLC (Pfizer Inc.)
• Inventors: Wozney, John M., Wang, Elizabeth A., Rosen, Vicki A.
• Primary Examiner(s): Furman, Keith C.
• Application Number:
  US07/721,847
• Time in Patent Office: 3,448 Days
• Field of Search: 530/350, 530/395, 514/12, 435/69.1
• US Class Current: 514/8.8
• 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: A61L 24/043 Mixtures of macromolecular materials
• CPC Class Codes: A61L 27/227 Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24
• CPC Class Codes: C07K 14/51 Bone morphogenetic factor; Osteogenins; Osteogenic factor; Bone-inducing factor
• CPC Class Codes: C08L 89/00 Compositions of proteins; Compositions of derivatives thereof foodstuff preparations A23J3/00
• CPC Class Codes: Y10S 930/12 Growth hormone, growth factor other than t-cell or b-cell growth factor, and growth hormone releasing factor; related peptides

Abstract

Purified BMP-2 and BMP-4 proteins and processes for producing them are disclosed. The proteins may be used in the treatment of bone and cartilage defects and in wound healing and related tissue repair.

Claims

1. A method for induction selected from the group consisting of the induction of bone formation, cartilage formation and the formation of the combination thereof in a patient comprising administering an amount of a purified BMP-2 protein effective for inducing said formation of bone, cartilage and the combination thereof said BMP-2 protein produced by the steps of:

(a) culturing under suitable conditions a cell transformed with a DNA sequence selected from the group consisting of

(i) a cDNA comprising the nucleotide sequence from nucleotide #356 to #1543 of SEQ ID NO;

3 encoding a subunit of BMP-2; and

(ii) DNA sequences comprising a nucleotide sequence which encodes a subunit having the 98 amino acid sequence from amino acid #17 to amino acid #114 of SEQ ID NO;

4

said DNA sequence in operative association with an expression control sequence therefor

(b) recovering and purifying from said culture medium a protein wherein each subunit comprises the 98 amino acid sequence from amino acid #17 to amino acid #114 of SEQ ID NO;

4 said protein having induction activity selected from the group consisting of bone, cartilage and the combination thereof.

2. The method of claim 1 wherein said induction comprises the induction of bone formation.

3. The method of claim 1 wherein said induction comprises the induction of cartilage formation.

4. The method of claim 1 wherein said induction comprises the induction of bone and cartilage formation.

5. The method of claim 1 wherein said BMP-2 protein comprises amino acids #1-114 of SEQ ID NO:

4.

6. The method of claim 1 wherein said cell is mammalian.

7. The method of claim 1 wherein said cell is a CHO cell.

8. A method for induction selected from the group consisting of the induction of bone formation, cartilage formation and the formation of the combination thereof in a patient comprising administering an amount of a purified BMP-4 protein effective for inducing said formation of bone, cartilage and the combination thereof said BMP-4 protein produced by the steps of

(a) culturing under suitable conditions a cell transformed with a DNA sequence selected from the group consisting of

(i) a cDNA comprising the nucleotide sequence from nucleotide #403 to #1626 of SEQ ID NO:

5 encoding a subunit of BMP-4; and

(ii) DNA sequences comprising a nucleotide sequence which encodes a subunit having the amino acid sequence from amino acid #19 to #116 of SEQ ID NO;

6

said DNA sequence in operative association with an expression control sequence therefor

(b) recovering and purifying from said culture medium a protein wherein each subunit comprises the 98 amino acid sequence from amino acid #19 to amino acid #116 of SEQ ID NO;

6 said protein having induction activity selected from the group consisting of bone, cartilage and the combination thereof.

9. The method of claim 8 wherein said induction comprises the induction of bone formation.

10. The method of claim 8 wherein said induction comprises the induction of cartilage formation.

11. The method of claim 8 wherein said induction comprises the induction of bone and cartilage formation.

12. The method of claim 8 wherein said BMP-4 protein comprises amino acids #1-#116 of SEQ ID NO:

6.

13. The method of claim 8 wherein said cell is mammalian.

14. The method of claim 8 wherein said cell is a CHO cell.