Glucagon receptor antagonists

• US 7,968,686 B2
• Filed: 03/17/2009
• Issued: 06/28/2011
• Est. Priority Date: 03/27/2008
• Status: Expired due to Fees

• Current Assignee: Eli Lilly and Company
• Original Assignee: Eli Lilly and Company
• Inventors: Millican, Rohn Lee Jr., Korytko, Andrew Ihor
• Primary Examiner(s): Goddard; Laura B
• Assistant Examiner(s): Natarajan; Meera
• Application Number:
  US12/405,458
• Publication Number:
  US 20090252727A1
• Time in Patent Office: 833 Days
• Field of Search: None
• US Class Current: 530/387.1
• 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. A humanized monoclonal antibody that inhibits binding of glucagon to a glucagon receptor, wherein said antibody comprises a light chain and a heavy chain, wherein

(i) the light chain comprises the CDRL1 of SEQ ID NO:

3, the CDRL2 of SEQ ID NO;

5 and the CDRL3 of SEQ ID NO;

6; and

(ii) the heavy chain comprises the CDRH1 of SEQ ID NO;

12, the CDRH2 of SEQ ID NO;

17 and the CDRH3 of SEQ ID NO;

21.

2. The humanized monoclonal antibody according to claim 1, wherein said light chain comprises the variable region sequence of SEQ ID NO:

45 and said heavy chain comprises the variable region sequence of SEQ ID NO;

47.

3. A humanized monoclonal antibody according to claim 2, comprising two light chains of SEQ ID NO:

65 and two heavy chains of SEQ ID NO;

67.

4. A pharmaceutical composition comprising an effective amount of a humanized monoclonal antibody according to claim 1 and a pharmaceutically acceptable excipient.