DNA sequences encoding

• US 5,116,738 A
• Filed: 04/26/1991
• Issued: 05/26/1992
• 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., Rosen, Vicki, Wang, Elizabeth A.
• Primary Examiner(s): Ellis, Joan
• Application Number:
  US07/692,827
• Time in Patent Office: 396 Days
• Field of Search: 435/69.1, 435/91, 435/172.3, 435/235.1, 435/320.1, 435/252.3, 435/252.33, 435/240.1, 435/240.2, 435/255, 435/256, 536/27, 530/350, 935/18, 935/31, 935/32, 935/58, 935/62, 935/70, 935/72, 935/73
• 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

Abstract

Purified BMP-3 proteins and processes for producing them are disclosed. They may be used in the treatment of bone and cartilage defects and in wound healing and related tissue repair.

Claims

1. An isolated DNA sequence encoding an osteoinductive protein said DNA sequence comprising a coding sequence selected from the group consisting of

(a) nucleostide #414 through nucleotide #746 of FIG. IA and #305 through nucleotide #493 of FIG. IB,

(b) nucleotide #321 through nucleotide #1736 of FIG. II,

(c) naturally occurring allelic sequences and equivalent degenerative codon sequences of (a) and (b);

and

(d) sequences which

(1) hybridize to any of sequences (a) and (b) or (c) under stringent hybridization conditions; and

(2)encode a protein characterized by the ability to induce the formation of bone and/or cartilage.

5. A vector comprising a DNA sequence of claim 1 in operative association with an expression control sequence for said DNA sequence.

8. A host cell transformed with the vector of claim 5 wherein said host cell is selected from the group consisting of mammalian, bacterial, yeast and insect cells.

13. A method of producing an osteoinductive protein, said method comprising the steps of

(a) culturing in a suitable culture medium said transformed host cell of claim 8;

and

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

14. The method of claim 13 wherein said host cell is a mammalian cell.

2. An isolated DNA sequence encoding an osteoinductive protein said DNA sequence comprising nucleotide #414 through #746 of FIG. 1A and nucleotide #305 through #493 of FIG. 1B.

3. An isolated DNA sequence encoding an osteoinductive protein said DNA sequence comprising nucleotide #321 through #1736 of FIG. 2.

6. A vector comprising a DNA sequence of claim 3 in operative association with an expression control sequence for said DNA sequence.

9. A host cell transformed with the vector of claim 6.

11. The host cell of claim 9 wherein said host is mammalian.

15. A method for producing an osteoinductive protein comprising the steps of:

(a) culturing in a suitable culture medium a host cell transformed with the vector of claim 6; and

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

17. The method of claim 15 wherein said host cell is a mammalian cell.

4. An isolated DNA sequence encoding an osteoinductive protein said DNA sequence comprising nudeotide #1 through #1794 of FIG. 2.

7. A vector comprising a DNA sequence of claim 4 in operative association with an expression control sequence for said DNA sequence.

10. A host cell transformed with the vector of claim 7.

12. The host cell of claim 10 wherein said host is mammalian.

16. A method for producing an osteoinductive protein comprising the step of:

(a) culturing in a suitable culture medium a host cell transformed with the vector of claim 7; and

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

18. The method of claim 16 wherein said host cell, is a mammalian cell.