Methods of increasing lean tissue mass using OB protein compositions

• US 20050176107A1
• Filed: 01/11/2005
• Published: 08/11/2005
• Est. Priority Date: 11/22/1995
• Status: Active Grant

• Current Assignee: Amgen Inc.
• Original Assignee: Amgen Inc.
• Inventors: Pelleymounter, Mary Ann, Toombs, Christopher Francis, Mann, Michael Benjamin
• Granted Patent: US 7,208,577 B2
• Time in Patent Office: Days
• US Class Current: 435/69.700
• CPC Class Codes: A61K 38/2264 Obesity-gene products, e.g. leptin
• CPC Class Codes: C07K 14/5759 Products of obesity genes, e.g. leptin, obese (OB), tub, fat
• CPC Class Codes: C07K 2319/30 Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto

Abstract

The present invention provides methods of creating and using OB protein compositions with an antibody constant region or portion thereof fused to an OB protein. The fusion protein is created by attaching the polyamino acids to the OB protein moiety. The fusion proteins can then be used for various therapeutic uses.

Claims

1. An isolated fusion protein comprising an Fc portion of an antibody attached at the N-terminus of an OB protein moiety comprising SEQ ID NO:

2 or an analog or derivative thereof.

2. A process of producing the fusion protein of claim 1, wherein the process comprises expressing a DNA sequence comprising a nucleic acid encoding the Fc portion of an antibody attached to SEQ ID NO:

1.

3. The isolated fusion protein of claim 1, wherein the Fc portion and the OB protein moiety are attached via a linker.

4. A process of producing the fusion protein of claim 3, wherein the process comprises expressing a DNA sequence comprising a nucleic acid encoding the Fc portion of an antibody attached to a nucleic acid encoding a linker, which linker nucleic acid is attached to SEQ ID NO:

1.

5. A vector comprising the DNA sequence of claim 2.

6. An isolated host cell transformed or transfected with the DNA sequence of claim 2.

7. The host cell of claim 6, wherein the host cell produces the fusion protein for use in increasing insulin sensitivity.

8. The host cell of claim 6, wherein the host cell produces the fusion protein for a use selected from decreasing the dose of insulin required for the treatment of diabetes, regulating bone resorption, and controlling serum glucose levels.

9. The host cell of claim 6, wherein the host cell produces the fusion protein for use in increasing lean tissue mass.

10. An isolated fusion protein comprising an Fc portion of an antibody attached at the N-terminus of an OB protein moiety comprising SEQ ID NO:

4 or an analog or derivative thereof.

11. The isolated fusion protein of claim 10, wherein, in the 146 residue sequence of SEQ ID NO:

4, lysine is substituted at position 35 and isoleucine is substituted at position 74.

12. A process of producing the isolated fusion protein of claim 11, wherein the process comprises expressing a DNA sequence comprising a nucleic acid encoding the Fc portion of an antibody attached to SEQ ID NO:

3, wherein the sequence of SEQ ID NO;

3 encoding position 35 of SEQ ID NO;

4 encodes lysine and the sequence of SEQ ID NO;

3 encoding position 74 of SEQ ID NO;

4 encodes isoleucine.

13. The isolated fusion protein of claim 10, wherein the Fc portion and the OB protein moiety are attached via a linker.

14. A process of producing the fusion protein of claim 13, wherein the process comprises expressing a DNA sequence comprising a nucleic acid encoding the Fc portion of an antibody attached to a nucleic acid encoding a linker, which linker nucleic acid is attached to SEQ ID NO:

3, wherein the sequence of SEQ ID NO;

3 encoding position 35 of SEQ ID NO;

4 encodes lysine and the sequence of SEQ ID NO;

3 encoding position 74 of SEQ ID NO;

4 encodes isoleucine.

15. A vector comprising the DNA sequence of claim 12.

16. An isolated host cell transformed or transfected with the DNA sequence of claim 12.

17. The host cell of claim 16, wherein the host cell produces the fusion protein for use in increasing insulin sensitivity.

18. The host cell of claim 16, wherein the host cell produces the fusion protein for use in decreasing the dose of insulin required for the treatment of diabetes.

19. The host cell of claim 16, wherein the host cell produces the fusion protein for use in regulating bone resorption or controlling serum glucose levels.

20. The host cell of claim 16, wherein the host cell produces the fusion protein for use in increasing lean tissue mass.