Recombinant bone morphogenetic protein heterodimers, compositions and methods of use

• US 7,678,885 B2
• Filed: 02/28/2003
• Issued: 03/16/2010
• Est. Priority Date: 11/04/1991
• Status: Expired due to Fees

• Current Assignee: Genetics Institute LLC (Pfizer Inc.)
• Original Assignee: Genetics Institute LLC (Pfizer Inc.)
• Inventors: Israel, David, Wolfman, Neil M.
• Primary Examiner(s): Stucker; Jeffrey
• Assistant Examiner(s): Dutt; Aditi
• Application Number:
  US10/375,150
• Publication Number:
  US 20030235888A1
• Time in Patent Office: 2,573 Days
• Field of Search: None
• 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 27/227 Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/51 Bone morphogenetic factor; Osteogenins; Osteogenic factor; Bone-inducing factor

Abstract

The present invention relates to a methods for producing recombinant heterodimeric BMP proteins useful in the field of treating bone defects, healing bone injury and in wound healing in general. The invention also relates to the recombinant heterodimers and compositions containing them.

Claims

1. An isolated recombinant dimeric protein having bone stimulating activity comprising a first bone morphogenetic protein-2 (BMP-2) subunit in association with a second BMP-2 subunit, wherein each subunit consists of an amino acid sequence selected from the group consisting of

(a) amino acids 249-396 of SEQ ID NO:

2;

(b) amino acids 266-396 of SEQ ID NO;

2;

(c) amino acids 283-396 of SEQ ID NO;

2; and

(d) amino acids 296-396 of SEQ ID NO;

2,

and wherein the first subunit and the second subunit do not have the same amino acid sequence.

2. A method for producing the dimeric protein of claim 1 comprising (a) co-expressing the first and second subunits of bone morphogenetic protein-2 in a selected host cell;

and (b) isolating the dimeric protein from the culture medium.