Bone morphogenetic protein -11 (BMP-11) compositions

• US 5,700,911 A
• Filed: 05/30/1995
• Issued: 12/23/1997
• Est. Priority Date: 05/12/1993
• Status: Expired due to Term

• Current Assignee: Genetics Institute LLC (Pfizer Inc.)
• Original Assignee: Genetics Institute LLC (Pfizer Inc.)
• Inventors: Wozney, John M., Celeste, Anthony J.
• Primary Examiner(s): Walsh, Stephen
• Assistant Examiner(s): Romeo, David S.
• Application Number:
  US08/452,772
• Time in Patent Office: 938 Days
• Field of Search: 536/23.4, 536/23.5, 536/23.51, 514/8, 514/12, 530/350, 530/399, 930/120, 435/69.4, 435/240.2, 435/252.3, 435/320.1
• US Class Current: 530/350
• CPC Class Codes: A61K 38/1875 Bone morphogenic factor; Osteogenins; Osteogenic factor; Bone-inducing factor
• CPC Class Codes: A61P 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/18 Feminine contraceptives
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: C07K 14/51 Bone morphogenetic factor; Osteogenins; Osteogenic factor; Bone-inducing factor
• CPC Class Codes: C07K 14/575 Hormones derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin C07K14/665, e.g. corticotropin C07K14/695
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: C12N 2501/155 Bone morphogenic proteins [BMP]; Osteogenins; Osteogenic factor; Bone inducing factor
• CPC Class Codes: C12N 5/0619 Neurons
• CPC Class Codes: Y10S 930/12 Growth hormone, growth factor other than t-cell or b-cell growth factor, and growth hormone releasing factor; related peptides

Abstract

Purified Bone Morphogenetic Protein-11(BMP-11) proteins and processes for producing them are disclosed. Recombinant DNA molecules encoding the BMP-11 proteins are also disclosed. The proteins may be useful in regulating follicle stimulating hormone, such as for contraception. In addition, the proteins may be useful for the induction of bone, cartilage and/or other connective tissue.

Claims

1. A purified Bone Morphogenetic Protein -11 (BMP-11 ) polypeptide consisting of the amino acid sequence from amino acid #1 to #109 as set forth in SEQ ID NO:

2.

2. A purified Bone Morphogenetic Protein -11 (BMP-11) polypeptide consisting of the amino acid sequence from amino acid #1 to #109 as set forth in SEQ ID NO:

11.

3. A purified BMP-11 polypeptide of claim 2 wherein said polypeptide is a dimer wherein each subunit consists of at least the amino acid sequence from amino acid #1 to #109 of SEQ ID NO:

11.

6. A purified BMP-11 polypeptide according to claim 2, wherein said polypeptide is a dimer wherein one subunit comprises at least the amino acid sequence from amino acid #1 to amino acid #109 of SEQ ID NO:

11, and one subunit comprises an amino acid sequence for a bone morphogenetic protein selected from the group consisting of BMP-1, BMP-2, BMP-3, BMP-4, BMP-5, BMP-6, BMP-7, BMP-8, BMP-9 and BMP-10.

7. A pharmaceutical composition comprising an effective amount for inducing bone and/or cartilage formation of the BMP-11 polypeptide of claim 11 in admixture with a pharmaceutically acceptable vehicle.

8. A pharmaceutical composition comprising an effective amount for inducing bone and/or cartilage formation of the BMP-11 polypeptide of claim 2 in admixture with a pharmaceutically acceptable vehicle.

9. A pharmaceutical composition comprising an effective amount for inducing bone and/or cartilage formation of a Bone Morphogenetic Protein -11 (BMP-11) polypeptide of claim 2, which is in dimeric form with another inhibin-β

protein, in admixture with a pharmaceutically acceptable vehicle.

10. A pharmaceutical composition comprising an effective amount for inducing bone and/or cartilage formation of a Bone Morphogenetic Protein -11 (BMP-11) polypeptide of claim 2, which is in dimeric form with an inhibin-α

protein, in admixture with a pharmaceutically acceptable vehicle.

11. A pharmaceutical composition comprising an effective amount for inducing bone and/or cartilage formation of a Bone Morphogenetic Protein -11 (BMP-11) polypeptide of claim 2, which is in dimeric form with a BMP protein, in admixture with a pharmaceutically acceptable vehicle.

12. A pharmaceutical composition comprising an effective amount for inducing bone and/or cartilage formation of a Bone Morphogenetic Protein -11 (BMP-1 1) polypeptide of claim 2, which is in dimeric form, wherein said composition further comprises at least one bone morphogenetic protein.

4. A purified Bone Morphogenetic Protein -11 (BMP-11) produced by the steps of

(a) culturing a mammalian cell transformed with a DNA molecule comprising the nucleotide sequence from nucleotide #375 to #704 as shown in SEQ ID NO:

1; and

(b) recovering and purifying from said culture medium a protein comprising the amino acid sequence from amino acid #1 to amino acid #109 of SEQ ID NO;

2.

5. A purified Bone Morphogenetic Protein -11 (BMP-11) produced by the steps of

(a) culturing a mammalian cell transformed with a DNA molecule comprising the nucleotide sequence from nucleotide #760 to #1086 as shown in SEQ ID NO:

10; and

(b) recovering and purifying from said culture medium a protein comprising the amino acid sequence from amino acid #1 to amino acid #109 as shown in SEQ ID NO;

11.