GLUCAGON RECEPTOR ANTAGONISTS

• US 20110212092A1
• Filed: 05/16/2011
• Published: 09/01/2011
• Est. Priority Date: 03/27/2008
• Status: Abandoned Application

• Current Assignee: Eli Lilly and Company
• Original Assignee: Eli Lilly and Company
• Inventors: KORYTKO, Andrew Ihor, MILLICAN, Rohn Lee JR.
• Application Number:
  US13/108,073
• Publication Number:
  US 20110212092A1
• Time in Patent Office: Days
• US Class Current: 424/133.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/50 for increasing or potentiating the activity of insulin
• CPC Class Codes: C07K 16/2869 against hormone receptors for antibodies against neuromediator receptors C07K16/286
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/55 Fab or Fab'
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

Abstract

The present invention relates to glucagon receptor polypeptide antagonists which inhibit the binding of the hormone glucagon to its receptor. More particularly, the present invention relates to high affinity glucagon receptor antibodies or Fab fragments thereof that inhibit binding of glucagon to its receptor and their use in the treatment or prevention of type 2 diabetes (NIDDM) and related disorders in mammalian species.

Claims

1-15. -15. (canceled)

16. A humanized monoclonal antibody that inhibits binding of glucagon to a glucagon receptor, wherein the antibody comprises a light chain and a heavy chain, wherein

(i) the light chain comprises

17. The humanized monoclonal antibody according to claim 16, wherein X is Y or A;

X₁ is I;

X₂ is Y;

X₃ is Q or L;

X₄ is Q or W;

X₅ is L or I;

X₆ is W or H;

X₇ is D or E;

X₈ is Y, Q, S or V;

X₉ is S;

X₁₀ is G or A;

X₁₁ is L.

18. The humanized monoclonal antibody according to claim 17, wherein X is A;

X₁ is I;

X₂ is Y;

X₃ is Q;

X₄ is Q;

X₅ is L;

X₆ is H;

X₇ is D or E;

X₈ is Y, Q or S;

X₉ is S;

X₁₀ is G or A;

X₁₁ is L.

19. A pharmaceutical composition comprising an effective amount of the humanized monoclonal antibody according to claim 18 and a pharmaceutically acceptable excipient.

20. A method of treating type 1 diabetes in a human, wherein the method comprises administrating an effective amount of the humanized monoclonal antibody according to claim 18 to a human patient in need thereof.

21. A method of treating type 2 diabetes in a human, wherein the method comprises administrating an effective amount of the humanized monoclonal antibody according to claim 18 to a human patient in need thereof.

22. A method for achieving weight loss in a human, wherein the method comprises administrating an effective amount of the humanized monoclonal antibody according to claim 18 to a human patient in need thereof.