GLP-1 analog fusion proteins

• US 8,273,854 B2
• Filed: 10/31/2008
• Issued: 09/25/2012
• Est. Priority Date: 06/12/2003
• Status: Active Grant

• Current Assignee: Eli Lilly and Company
• Original Assignee: Eli Lilly and Company
• Inventors: Glaesner, Wolfgang, Millican, Rohn Lee Jr., Vick, Andrew Mark
• Primary Examiner(s): Tsang, Cecilia J
• Assistant Examiner(s): Niebauer, Ronald T
• Application Number:
  US12/262,832
• Publication Number:
  US 20090074769A1
• Time in Patent Office: 1,425 Days
• Field of Search: None
• US Class Current: 530/324
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• 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 5/48 of the pancreatic hormones
• CPC Class Codes: C07K 14/503 basic FGF [bFGF]
• CPC Class Codes: C07K 14/605 Glucagons
• CPC Class Codes: C07K 16/26 against hormones ; against hormone releasing or inhibiting factors
• 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 invention provides specific GLP-1 analogs fused to specific IgG4-Fc derivatives. These fusion proteins have an increased half-life, decreased immunogenicity, and reduce effector activity. The fusion proteins are useful in treating diabetes, obesity, irritable bowel syndrome and other conditions that would be benefited by lowering plasma glucose, inhibiting gastric and/or intestinal motility and inhibiting gastric and/or intestinal emptying, or inhibiting food intake.

Claims

1. A method of treating a patient with non-insulin dependent diabetes mellitus comprising administering to the patient a therapeutically effective amount of a heterologous fusion protein comprising:

a GLP-1 analog comprising SEQ ID NO;

1

5. The method according to any one of claims 1 to 4 wherein the fusion protein is produced by expressing the fusion protein in a mammalian host cell.

6. The method according to claim 5 wherein the host cell is a CHO cell.

2. A method of treating a patient with non-insulin dependent diabetes mellitus comprising administering to the patient a therapeutically effective amount of a heterologous fusion protein consisting of:

a GLP-1 analog consisting of SEQ ID NO;

1

3. A method of treating a patient with non-insulin dependent diabetes mellitus comprising administering to the patient a therapeutically effective amount of a heterologous fusion protein comprising a dimer comprising two chains joined together by disulfide bonds wherein each chain has:

a GLP-1 analog consisting of SEQ ID NO;

1

4. A method of treating a patient with non-insulin dependent diabetes mellitus comprising administering to the patient a therapeutically effective amount of a heterologous fusion protein comprising a dimer comprising two chains joined together by disulfide bonds wherein each chain has:

a GLP-1 analog consisting of SEQ ID NO;

1