Bone morphogenic protein-5(BMP-5) and DNA encoding same

• US 5,635,373 A
• Filed: 06/06/1995
• Issued: 06/03/1997
• 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): Walsh, Stephen G.
• Assistant Examiner(s): KEMMERER, ELIZABETH
• Application Number:
  US08/469,935
• Time in Patent Office: 728 Days
• Field of Search: 435/69.1, 435/172.3, 435/240.2, 435/252.3, 435/320.1, 530/350, 530/395, 536/23.5
• US Class Current: 435/69.1
• 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 method for producing a purified bone morphogenic protein-5 (BMP-5) said method comprising the steps of

(a) culturing in a suitable culture medium cells transformed with a DNA sequence comprising the DNA sequence from nucleotide #699 to #2060 of Table III;

and

(b) isolating and purifying said protein from said culture medium.

2. An isolated DNA sequence encoding a bone morphogenic protein (BMP-5) comprising:

(a) nucleotide #1647 through #2060 of Table III; and

(b) naturally occurring allelic sequences and equivalent degenerative codon sequences thereof.

3. A vector comprising a DNA sequence of claim 2 in operative association with an expression control sequence therefor.

4. A host cell transformed with the vector of claim 3.

5. The host cell of claim 4 wherein said host cell is a mammalian cell.

6. The host cell of claim 4 wherein said host cell is a CHO cell.

7. A method for producing a bone morphogenic protein-5 (BMP-5) comprising:

(a) transforming a host cell with a vector comprising nucleotide #1647 to #2060 of Table III;

(b) culturing said transformed host cell in a suitable culture medium;

(c) isolating and purifying said BMP-5 from said culture medium.

8. The method of claim 7 wherein said host cell is CHO.

9. A method for producing a bone morphogenic protein-5 (BMP-5) comprising:

(a) transforming a host cell with a vector comprising nucleotide #1665 to #2060 of Table III;

(b) culturing said transformed host cell in a suitable culture medium;

(c) isolating and purifying said BMP-5 protein from said culture medium.

10. The method of claim 9 wherein said host cell is CHO.

11. A method for producing a bone morphogenic protein-5 (BMP-5) comprising:

(a) transforming a host cell with a vector comprising nucleotide #1 to #2060 of Table III;

(b) culturing said transformed host cell in a suitable culture medium;

(c) isolating and purifying said BMP-5 from said culture medium.

12. The method of claim 11 wherein said host cell is CHO.

13. A composition comprising an isolated and purified (1) protein having the amino acid sequence from amino acid #317 (Ala) to amino acid #454 (His) as shown in Table III or naturally occurring allelic sequences thereof, and (2) a carrier or a matrix.

14. A composition comprising an isolated and purified (1) protein having the amino acid sequence from amino acid #323 (Asn) to amino acid #454 (His) as shown in Table III or naturally occurring allelic sequences thereof, and (2) a carrier or a matrix.

15. A composition comprising an isolated and purified (1) protein having the amino acid sequence from amino acid #1 (Met) to amino acid #454 (His) as shown in Table III or naturally occurring allelic sequences thereof, and (2) a carrier or a matrix.

16. A composition comprising (1) 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 or naturally occurring allelic sequences thereof, and (2) a carrier or a matrix.

17. A composition comprising (1) 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 or naturally occurring allelic sequences thereof, and (2) a carrier or a matrix.

18. A composition comprising (1) an isolated and purified protein dimer with at least one of the subunits having the amino acid sequence from amino acid #1 (Met) to amino acid #454 (His) of Table III or naturally occurring allelic sequences thereof, and (2) a carrier or a matrix.

19. A composition comprising (1) 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 or naturally occurring allelic sequences thereof, and (2) a carrier or a matrix.

20. An isolated DNA sequence encoding a bone morphogenic protein-5 (BMP-5) comprising:

(a) nucleotide #1665 through #2060 of Table III;

or

(b) naturally occurring allelic sequences or equivalent degenerative codon sequences thereof.

21. An isolated DNA sequence encoding a bone morphogenic protein-5 (BMP-5) comprising:

(a) nucleotide #1 through #2060 of Table III;

or

(b) naturally occurring allelic sequences or equivalent degenerative codon sequences thereof.

22. An isolated DNA sequence encoding a bone morphogenic protein-5 (BMP-5) comprising:

(a) nucleotide #699 through #2060 of Table III;

or

(b) naturally occurring allelic sequences or equivalent degenerative codon sequences thereof.