Use of adipsin/complement factor D in the treatment of metabolic related disorders

• US 20030092620A1
• Filed: 07/22/2002
• Published: 05/15/2003
• Est. Priority Date: 07/26/2001
• Status: Active Grant

• Current Assignee: Serono Genetics Institute S.A. (Merck & Co., Inc.)
• Original Assignee: Genset SA
• Inventors: Lucas, John, Briggs, Kristen
• Granted Patent: US 6,867,189 B2
• Time in Patent Office: Days
• US Class Current: 514/4.8
• CPC Class Codes: A61K 38/1709 from mammals

Abstract

The present invention relates to the field of metabolic research. Metabolic disorders, such as obesity, are a public health problem that is serious and widespread. Adipsin polypeptides have been identified that are believed to be beneficial in the treatment of metabolic disorders. These compounds should be effective for reducing body mass and for treating metabolic-related diseases and disorders. These metabolic-related diseases and disorders include hyperlipidemias, atherosclerosis, insulin resistance, diabetes, and hypertension.

Claims

1. A method of reducing body mass in an individual comprising administering to said individual a composition comprising an Adipsin polypeptide selected from amino acids 21-253 or 26-253 of SEQ ID NO:

2 where amino acid 21 of SEQ ID NO;

2 is predicted to be the N-terminal amino acid of the mature Adipsin polypeptide absent the putative signal peptide and amino acid 26 of SEQ ID NO;

2 is predicted to be the N-terminal amino acid of the mature Adipsin polypeptide absent both the putative signal peptide and the putative activation peptide, amino acids 20-253 or 26-253 of SEQ ID NO;

4 where amino acid 20 of SEQ ID NO;

4 is predicted to be the N-terminal amino acid of the mature Adipsin polypeptide absent the putative signal peptide and amino acid 26 of SEQ ID NO;

4 is predicted to be the N-terminal amino acid of the mature Adipsin polypeptide absent both the putative signal peptide and the putative activation peptide, or amino acids 1-228 or 2-228 of SEQ ID NO;

6, and a proteolytically active fragment of SEQ ID NOs;

2, 4 or 6, said composition further optionally comprising Apm1 polypeptide.

2. A method of lowering circulating glucose levels in an individual comprising administering to said individual a composition comprising an Adipsin polypeptide selected from amino acids 21-253 or 26-253 of SEQ ID NO:

2 where amino acid 21 of SEQ ID NO;

2 is predicted to be the N-terminal amino acid of the mature Adipsin polypeptide absent the putative signal peptide and amino acid 26 of SEQ ID NO;

2 is predicted to be the N-terminal amino acid of the mature Adipsin polypeptide absent both the putative signal peptide and the putative activation peptide, amino acids 20-253 or 26-253 of SEQ ID NO;

4 where amino acid 20 of SEQ ID NO;

4 is predicted to be the N-terminal amino acid of the mature Adipsin polypeptide absent the putative signal peptide and amino acid 26 of SEQ ID NO;

4 is predicted to be the N-terminal amino acid of the mature Adipsin polypeptide absent both the putative signal peptide and the putative activation peptide, or amino acids 1-228 or 2-228 of SEQ ID NO;

6, and a proteolytically active fragment of SEQ ID NOs;

2, 4 or 6, said composition further optionally comprising Apm1 polypeptide.

3. A method of lowering circulating free fatty acid levels in an individual comprising administering to said individual a composition comprising an Adipsin polypeptide selected from amino acids 21-253 or 26-253 of SEQ ID NO:

2 where amino acid 21 of SEQ ID NO;

2 is predicted to be the N-terminal amino acid of the mature Adipsin polypeptide absent the putative signal peptide and amino acid 26 of SEQ ID NO;

2 is predicted to be the N-terminal amino acid of the mature Adipsin polypeptide absent both the putative signal peptide and the putative activation peptide, amino acids 20-253 or 26-253 of SEQ ID NO;

4 where amino acid 20 of SEQ ID NO;

4 is predicted to be the N-terminal amino acid of the mature Adipsin polypeptide absent the putative signal peptide and amino acid 26 of SEQ ID NO;

4 is predicted to be the N-terminal amino acid of the mature Adipsin polypeptide absent both the putative signal peptide and the putative activation peptide, or amino acids 1-228 or 2-228 of SEQ ID NO;

6, and a proteolytically active fragment of SEQ ID NOs;

2, 4 or 6, said composition further optionally comprising Apm1 polypeptide.

4. A method of lowering circulating triglyceride levels in an individual comprising administering to said individual a composition comprising an Adipsin polypeptide selected from amino acids 21-253 or 26-253 of SEQ ID NO:

2 where amino acid 21 of SEQ ID NO;

2 is predicted to be the N-terminal amino acid of the mature Adipsin polypeptide absent the putative signal peptide and amino acid 26 of SEQ ID NO;

2 is predicted to be the N-terminal amino acid of the mature Adipsin polypeptide absent both the putative signal peptide and the putative activation peptide, amino acids 20-253 or 26-253 of SEQ ID NO;

4 where amino acid 20 of SEQ ID NO;

4 is predicted to be the N-terminal amino acid of the mature Adipsin polypeptide absent the putative signal peptide and amino acid 26 of SEQ ID NO;

4 is predicted to be the N-terminal amino acid of the mature Adipsin polypeptide absent both the putative signal peptide and the putative activation peptide, or amino acids 1-228 or 2-228 of SEQ ID NO;

6, and a proteolytically active fragment of SEQ ID NOs;

2, 4 or 6, said composition further optionally comprising Apm1 polypeptide.

5. A method of lowering circulating cholesterol levels in an individual comprising administering to said individual a composition comprising an Adipsin polypeptide selected from amino acids 21-253 or 26-253 of SEQ ID NO:

2 where amino acid 21 of SEQ ID NO;

2 is predicted to be the N-terminal amino acid of the mature Adipsin polypeptide absent the putative signal peptide and amino acid 26 of SEQ ID NO;

2 is predicted to be the N-terminal amino acid of the mature Adipsin polypeptide absent both the putative signal peptide and the putative activation peptide, amino acids 20-253 or 26-253 of SEQ ID NO;

4 where amino acid 20 of SEQ ID NO;

4 is predicted to be the N-terminal amino acid of the mature Adipsin polypeptide absent the putative signal peptide and amino acid 26 of SEQ ID NO;

4 is predicted to be the N-terminal amino acid of the mature Adipsin polypeptide absent both the putative signal peptide and the putative activation peptide, or amino acids 1-228 or 2-228 of SEQ ID NO;

6, and a proteolytically active fragment of SEQ ID NOs;

2, 4 or 6, said composition further optionally comprising Apm1 polypeptide.

6. A method of increasing glucose oxidation in skeletal muscle in an individual comprising administering to said individual a composition comprising an Adipsin polypeptide selected from amino acids 21-253 or 26-253 of SEQ ID NO:

2 where amino acid 21 of SEQ ID NO;

2 is predicted to be the N-terminal amino acid of the mature Adipsin polypeptide absent the putative signal peptide and amino acid 26 of SEQ ID NO;

2 is predicted to be the N-terminal amino acid of the mature Adipsin polypeptide absent both the putative signal peptide and the putative activation peptide, amino acids 20-253 or 26-253 of SEQ ID NO;

4 where amino acid 20 of SEQ ID NO;

4 is predicted to be the N-terminal amino acid of the mature Adipsin polypeptide absent the putative signal peptide and amino acid 26 of SEQ ID NO;

4 is predicted to be the N-terminal amino acid of the mature Adipsin polypeptide absent both the putative signal peptide and the putative activation peptide, or amino acids 1-228 or 2-228 of SEQ ID NO;

6, and a proteolytically active fragment of SEQ ID NOs;

2, 4 or 6, said composition further optionally comprising Apm1 polypeptide.

7. A method of increasing free fatty oxidation in skeletal muscle in an individual comprising administering to said individual a composition comprising an Adipsin polypeptide selected from amino acids 21-253 or 26-253 of SEQ ID NO:

2 where amino acid 21 of SEQ ID NO;

2 is predicted to be the N-terminal amino acid of the mature Adipsin polypeptide absent the putative signal peptide and amino acid 26 of SEQ ID NO;

2 is predicted to be the N-terminal amino acid of the mature Adipsin polypeptide absent both the putative signal peptide and the putative activation peptide, amino acids 20-253 or 26-253 of SEQ ID NO;

4 where amino acid 20 of SEQ ID NO;

4 is predicted to be the N-terminal amino acid of the mature Adipsin polypeptide absent the putative signal peptide and amino acid 26 of SEQ ID NO;

4 is predicted to be the N-terminal amino acid of the mature Adipsin polypeptide absent both the putative signal peptide and the putative activation peptide, or amino acids 1-228 or 2-228 of SEQ ID NO;

6, and a proteolytically active fragment of SEQ ID NOs;

2, 4 or 6, said composition further optionally comprising Apm1 polypeptide.

8. A method of treating insulin resistance in an individual comprising administering to said individual a composition comprising an Adipsin polypeptide selected from amino acids 21-253 or 26-253 of SEQ ID NO:

2 where amino acid 21 of SEQ ID NO;

2 is predicted to be the N-terminal amino acid of the mature Adipsin polypeptide absent the putative signal peptide and amino acid 26 of SEQ ID NO;

2 is predicted to be the N-terminal amino acid of the mature Adipsin polypeptide absent both the putative signal peptide and the putative activation peptide, amino acids 20-253 or 26-253 of SEQ ID NO;

4 where amino acid 20 of SEQ ID NO;

4 is predicted to be the N-terminal amino acid of the mature Adipsin polypeptide absent the putative signal peptide and amino acid 26 of SEQ ID NO;

4 is predicted to be the N-terminal amino acid of the mature Adipsin polypeptide absent both the putative signal peptide and the putative activation peptide, or amino acids 1-228 or 2-228 of SEQ ID NO;

6, and a proteolytically active fragment of SEQ ID NOs;

2, 4 or 6, said composition further optionally comprising Apm1 polypeptide.

9. A method of treating type I diabetes in an individual comprising administering to said individual a composition comprising an Adipsin polypeptide selected from amino acids 21-253 or 26-253 of SEQ ID NO:

2 where amino acid 21 of SEQ ID NO;

2 is predicted to be the N-terminal amino acid of the mature Adipsin polypeptide absent the putative signal peptide and amino acid 26 of SEQ ID NO;

2 is predicted to be the N-terminal amino acid of the mature Adipsin polypeptide absent both the putative signal peptide and the putative activation peptide, amino acids 20-253 or 26-253 of SEQ ID NO;

4 where amino acid 20 of SEQ ID NO;

4 is predicted to be the N-terminal amino acid of the mature Adipsin polypeptide absent the putative signal peptide and amino acid 26 of SEQ ID NO;

4 is predicted to be the N-terminal amino acid of the mature Adipsin polypeptide absent both the putative signal peptide and the putative activation peptide, or amino acids 1-228 or 2-228 of SEQ ID NO;

6, and a proteolytically active fragment of SEQ ID NOs;

2, 4 or 6, said composition further optionally comprising Apm1 polypeptide.

10. A method of treating type II diabetes in an individual comprising administering to said individual a composition comprising an Adipsin polypeptide selected from amino acids 21-253 or 26-253 of SEQ ID NO:

2 where amino acid 21 of SEQ ID NO;

2 is predicted to be the N-terminal amino acid of the mature Adipsin polypeptide absent the putative signal peptide and amino acid 26 of SEQ ID NO;

2 is predicted to be the N-terminal amino acid of the mature Adipsin polypeptide absent both the putative signal peptide and the putative activation peptide, amino acids 20-253 or 26-253 of SEQ ID NO;

4 where amino acid 20 of SEQ ID NO;

4 is predicted to be the N-terminal amino acid of the mature Adipsin polypeptide absent the putative signal peptide and amino acid 26 of SEQ ID NO;

4 is predicted to be the N-terminal amino acid of the mature Adipsin polypeptide absent both the putative signal peptide and the putative activation peptide, or amino acids 1-228 or 2-228 of SEQ ID NO;

6, and a proteolytically active fragment of SEQ ID NOs;

2, 4 or 6, said composition further optionally comprising Apm1 polypeptide.

11. A method of treating syndrome X in an individual comprising administering to said individual a composition comprising an Adipsin polypeptide selected from amino acids 21-253 or 26-253 of SEQ ID NO:

2 where amino acid 21 of SEQ ID NO;

2 is predicted to be the N-terminal amino acid of the mature Adipsin polypeptide absent the putative signal peptide and amino acid 26 of SEQ ID NO;

2 is predicted to be the N-terminal amino acid of the mature Adipsin polypeptide absent both the putative signal peptide and the putative activation peptide, amino acids 20-253 or 26-253 of SEQ ID NO;

4 where amino acid 20 of SEQ ID NO;

4 is predicted to be the N-terminal amino acid of the mature Adipsin polypeptide absent the putative signal peptide and amino acid 26 of SEQ ID NO;

4 is predicted to be the N-terminal amino acid of the mature Adipsin polypeptide absent both the putative signal peptide and the putative activation peptide, or amino acids 1-228 or 2-228 of SEQ ID NO;

6, and a proteolytically active fragment of SEQ ID NOs;

2, 4 or 6, said composition further optionally comprising Apm1 polypeptide.

12. A method of treating atherosclerosis in an individual comprising administering to said individual a composition comprising an Adipsin polypeptide selected from amino acids 21-253 or 26-253 of SEQ ID NO:

2 where amino acid 21 of SEQ ID NO;

2 is predicted to be the N-terminal amino acid of the mature Adipsin polypeptide absent the putative signal peptide and amino acid 26 of SEQ ID NO;

2 is predicted to be the N-terminal amino acid of the mature Adipsin polypeptide absent both the putative signal peptide and the putative activation peptide, amino acids 20-253 or 26-253 of SEQ ID NO;

4 where amino acid 20 of SEQ ID NO;

4 is predicted to be the N-terminal amino acid of the mature Adipsin polypeptide absent the putative signal peptide and amino acid 26 of SEQ ID NO;

4 is predicted to be the N-terminal amino acid of the mature Adipsin polypeptide absent both the putative signal peptide and the putative activation peptide, or amino acids 1-228 or 2-228 of SEQ ID NO;

6, and a proteolytically active fragment of SEQ ID NOs;

2, 4 or 6, said composition further optionally comprising Apm1 polypeptide.

13. An isolated Adipsin polypeptide selected from amino acids 21-253 or 26-253 of SEQ ID NO:

2 where amino acid 21 of SEQ ID NO;

2 is predicted to be the N-terminal amino acid of the mature Adipsin polypeptide absent the putative signal peptide and amino acid 26 of SEQ ID NO;

2 is predicted to be the N-terminal amino acid of the mature Adipsin polypeptide absent both the putative signal peptide and the putative activation peptide, amino acids 20-253 or 26-253 of SEQ ID NO;

4 where amino acid 20 of SEQ ID NO;

4 is predicted to be the N-terminal amino acid of the mature Adipsin polypeptide absent the putative signal peptide and amino acid 26 of SEQ ID NO;

4 is predicted to be the N-terminal amino acid of the mature Adipsin polypeptide absent both the putative signal peptide and the putative activation peptide, or amino acids 1-228 or 2-228 of SEQ ID NO;

6, and a proteolytically active fragment of SEQ ID NOs;

2, 4 or 6.

14. A composition comprising a carrier and the Adipsin polypeptide of claim 13, said composition further optionally comprising Apm1 polypeptide.

15. An isolated polynucleotide, or complement thereof, encoding the Adipsin polypeptide of claim 13.

16. A composition comprising a carrier and an isolated polynucleotide according to claim 15.

17. A vector comprising an isolated polynucleotide sequence encoding the Adipsin polypeptide of claim 13.

18. A composition comprising a carrier and a vector of claim 17.

19. A transformed host cell comprising the vector according to claim 17.