Bone and cartilage inductive proteins

• US 7,378,392 B1
• Filed: 10/06/1994
• Issued: 05/27/2008
• Est. Priority Date: 05/16/1990
• Status: Expired due to Fees

• Current Assignee: Genetics Institute LLC (Pfizer Inc.)
• Original Assignee: Genetics Institute LLC (Pfizer Inc.)
• Inventors: Wang, Jack H., Wozney, John M., Hewick, Rodney M., Celeste, Anthony J.
• Primary Examiner(s): KEMMERER, ELIZABETH
• Application Number:
  US08/319,831
• Time in Patent Office: 4,982 Days
• Field of Search: 530/350, 530/395, 530/399, 530/300, 435/69.1, 435/69.4, 424/422, 424/423, 424/425, 424/426, 514/12, 514/21, 514/2, 536/23.51, 536/23.5
• US Class Current: 514/9.4
• 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: C07K 14/51 Bone morphogenetic factor; Osteogenins; Osteogenic factor; Bone-inducing factor

Abstract

Purified cartilage and/or bone inductive 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 purified BMP-8 protein characterized by:

(a) at least one of the following sequences;

i) Arg-His-Glu-Leu-Tyr-Val-Ser-Phe-Gln-Asp-Leu-Gly-Trp-Leu-Asp-Trp-Val-Ile-Ala-Pro-Gln-Gly-Tyr (SEQ ID NO;

     1);

ii) Leu-Ser-Ala-Thr-Ser-Val-Leu-Tyr-Tyr-Asp-Ser-Ser-Asn-Asn-Val-Ile-Leu-Arg (SEQ ID NO;

     2); and

iii) Ala-Cys-Cys-Ala-Pro-Thr-Lys (SEQ ID NO;

     3);

(b) a molecular weight of 28,000-38,000 daltons as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis; and

(c) a molecular weight of 14,400-20,000 daltons under reducing conditions as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis said protein being a disulfide linked dimer wherein each of the subunits contains the sequences set forth in part (a) and said protein having the ability to induce the formation of cartilage and/or bone.

2. A pharmaceutical formulation for bone and/or cartilage formation comprising an effective amount of a BMP-8 protein of claim 1 in a pharmaceutically acceptable vehicle.

3. A composition of claim 2 further comprising a matrix for supporting said composition and providing a surface for bone and/or cartilage formation.

4. The composition of claim 3 wherein said matrix comprises a material selected from the group consisting of hydroxyapatite, collagen, polylactic acid and tricalcium phosphate.

5. A pharmaceutical composition for wound healing and tissue repair said composition comprising an effective amount of a BMP-8 protein of claim 1 in a pharmaceutically acceptable vehicle.

6. The BMP-8 protein of claim 1, wherein the BMP-8 is human BMP-8.