BMP-4 products

• US 6,245,889 B1
• Filed: 09/09/1997
• Issued: 06/12/2001
• 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): Romeo, David S.
• Application Number:
  US08/925,779
• Time in Patent Office: 1,372 Days
• Field of Search: 530/350, 530/300, 514/12, 435/69.1
• 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: 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 BMP-4 protein produced by

(a) culturing a host cell transformed with a DNA sequence comprising nucleotides 1279 through 1626 of FIG. 3;

and

(b) recovering said BMP-4 protein comprising amino acids 311 through 408 of FIG. 3.

2. A purified BMP-4 protein comprising amino acids 293 through 408 of FIG. 3.

3. A pharmaceutical composition comprising a cartilage and/or bone inducing amount of a BMP-4 polypeptide of claim 2.

4. The protein of claim 2 wherein said protein is a disulfide-linked dimer comprising two subunits wherein each of said subunits comprises amino acids 293 through 408 of FIG. 3.

5. A pharmaceutical composition comprising a cartilage and/or bone inducing amount of a BMP-4 protein of claim 2 in admixture with a pharmaceutically acceptable vehicle.

6. A composition of claim 5 comprising a matrix for supporting said composition and providing a surface for bone and/or cartilage growth.

7. The composition of claim 6 wherein said matrix comprises a material selected from the group consisting of hydroxyapatite, collagen, polylactic acid and tricalcium phosphate.

8. A composition for bone and/or cartilage formation comprising a bone and/or cartilage inducing amount of a BMP-4 protein of claim 2 in a pharmaceutically acceptable vehicle.

9. A composition comprising a bone and/or cartilage inducing amount of a BMP-4 protein comprising amino acids 311 through 408 of FIG. 3 in a pharmaceutically acceptable vehicle.

10. A composition of claim 9 further comprising a matrix for supporting said composition and providing a surface for bone and/or cartilage growth.

11. The composition of claim 10 wherein said matrix comprises a material selected from the group consisting of hydroxyapatite, collagen, polylactic acid and tricalcium phosphate.

12. A purified bone morphogenetic protein-4 (BMP-4 ), wherein said BMP-4 is a disulfide-linked dimer comprising two subunits wherein each of said subunits comprises amino acids 311 through 408 of FIG. 3.

13. A BMP-4 protein produced by

(a) culturing a host cell transformed with a DNA sequence comprising nucleotides 1333 through 1626 of FIG. 3;

and

(b) recovering said BMP-4 protein comprising amino acids 311 through 408 of FIG. 3.

14. A purified bone morphogenetic protein (BMP)-4 wherein said BMP is a disulfide-linked heterodimer comprising two subunits wherein one subunit comprises an amino acid sequence selected from the group consisting of

(a) amino acids 293 through 408 of FIG. 3, and

(b) amino acids 311 through 408 of FIG. 3;

and wherein the other subunit is selected from the group consisting of a subunit of a BMP selected from the group consisting of BMP-2, BMP-3, BMP-5, BMP-6, BMP-7, and BMP-8.

15. A purified bone morphogenetic protein (BMP)-4 wherein said BMP is a disulfide-linked dimer comprising two subunits wherein one subunit comprises an amino acid sequence selected from the group consisting of

(a) amino acids 293 through 408 of FIG. 3, and

(b) amino acids 311 through 408 of FIG. 3;

and wherein the other subunit comprises an amino acid sequence selected from the group consisting of

(a) amino acids 293 through 408 of FIG. 3, and

(b) amino acids 311 through 408 of FIG. 3.