Bone morphogenetic protein 5(BMP-5) compositions

• US 5,543,394 A
• Filed: 09/07/1993
• Issued: 08/06/1996
• Est. Priority Date: 07/01/1986
• Status: Expired due to Fees

• 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): Walsh, Stephen G.
• Application Number:
  US08/116,425
• Time in Patent Office: 1,064 Days
• Field of Search: 530/350, 530/395, 530/399, 514/12, 435/69.1, 424/484
• 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: C12N 15/85 for animal cells
• CPC Class Codes: C12N 2800/108 episomal vectors
• CPC Class Codes: C12N 2840/20 translation of more than one cistron

Abstract

Purified BMP-5 proteins and processes for producing them are disclosed. The proteins may be used in the treatment of bone and/or cartilage defects and in wound healing and related tissue repair.

Claims

1. A composition comprising an isolated and purified protein having the amino acid sequence from amino acid #317 (Ala) to amino acid #454 (His) as shown in Table III said protein further characterized by the ability to induce the formation of cartilage and bone.

5. The composition of claim 1 further comprising a matrix supporting said protein and providing a surface for bone and cartilage growth.

6. The composition of claim 5 wherein said matrix comprises a material selected from the group consisting of hydroxyapatite, collagen, polylactic acid and tricalcium phosphate.

7. A method for inducing bone and cartilage formation in a patient in need of same comprising administering to said patient an effective amount of the composition of claim 1.

2. A composition comprising an isolated and purified protein having the amino acid sequence from amino acid #323 (Asn) to #454 (His) as shown in Table III said protein further characterized by the ability to induce the formation of cartilage and bone.

17. The composition of claim 2 further comprising a matrix supporting said protein and providing a surface for bone and cartilage growth.

3. A composition comprising an isolated and purified protein produced by the steps of

(a) culturing a cell transformed with a vector comprising the DNA sequence of Table III from nucleotide #1665 to #2060;

and

(b) recovering from the resulting culture medium said protein having the amino acid sequence from amino acid #323 (Asn) to amino acid #454 (His) as shown in Table III said protein further characterized by the ability to induce the formation of cartilage and bone.

14. The composition of claim 3 wherein said transformed cell is mammalian.

4. A composition comprising a purified protein produced by the steps of

(a) culturing a cell transformed with a vector comprising the DNA sequence of Table III from nucleotide #699 to #2060;

and

(b) recovering from the resulting culture medium a protein having the amino acid sequence from amino acid #317 (Ala) to amino acid #454 (His) as shown in Table III said protein further characterized by the ability to induce the formation of cartilage and bone.

18. The composition of claim 4 wherein said transformed cell is mammalian.

8. A composition comprising an isolated and purified protein having an amino acid sequence selected from the group consisting of

a) amino acid #317 (Ala) to #454 (His) of Table III;

b) amino acid #323 (Asn) to #454 (His) of Table III;

c) amino acid #1 (Met) to #454 (His) of Table III; and

d) the amino acid sequence of Table I;

said protein characterized by the ability to induce the formation of cartilage and bone.

9. A composition comprising an isolated and purified protein having the amino acid sequence from amino acid #1 (Met) to #454 (His) of Table III said protein characterized by the ability to induce the formation of cartilage and bone.

10. A composition comprising an isolated and purified protein dimer with at least one of the subunits having the amino acid sequence from amino acid #317 (Ala) to amino acid #454 (His) of Table III said protein characterized by the ability to induce the formation of cartilage and bone.

11. A composition comprising an isolated and purified protein dimer with at least one of the subunits having the amino acid sequence from amino acid #323 (Asn) to amino acid #454 (His) of Table III said protein characterized by the ability to induce the formation of cartilage and bone.

12. A composition comprising an isolated and purified protein dimer with at least one of the subunits having the amino acid sequence from amino acid #28 (Gly) to amino acid #454 (His) of Table III said protein characterized by the ability to induce the formation of cartilage and bone.

13. A composition comprising an isolated and purified protein produced by the steps of

(a) culturing a cell transformed with a vector comprising a DNA sequence having the sequence of Table III from nucleotide #1647 to #2060;

and

(b) recovering from the resulting culture medium said protein the amino acid sequence from amino acid #317 (Ala) to amino acid #454 (His) as shown in Table III

said protein characterized by the ability to induce the formation of cartilage and bone.

19. The composition of claim 13 wherein said transformed cell is mammalian.

15. A composition comprising an isolated and purified protein encoded by the DNA sequence encoding the BMP-5 of ATCC 68019 said protein characterized by the ability to induce the formation of cartilage and bone.

16. A composition comprising an isolated and purified protein having the amino acid sequence of Table I said protein characterized by the ability to induce the formation of cartilage and bone.

20. A bone morphogenetic protein-5 (BMP-5) produced by culturing a cell transformed with a vector comprising the DNA sequence of Table III from nucleotide #699 to nucleotide #2070 and recovering said protein from the resulting culture medium.