Method of treating stomach or bowel-related disorders by administering glucagon-like-peptide-2 (GLP-2) analogues

• US 9,580,487 B2
• Filed: 09/08/2015
• Issued: 02/28/2017
• Est. Priority Date: 05/04/2005
• Status: Active Grant

• Current Assignee: Zealand Pharma A/S
• Original Assignee: Zealand Pharma A/S
• Inventors: Larsen, Bjarne Due, Petersen, Yvette Miata
• Primary Examiner(s): Bunner, Bridget E
• Application Number:
  US14/847,938
• Publication Number:
  US 20150368314A1
• Time in Patent Office: 539 Days
• US Class Current: 1/1
• CPC Class Codes: A61K 35/54 Ovaries; Ova; Ovules; Embryos; Foetal cells; Germ cells
• CPC Class Codes: A61K 35/74 Bacteria therapeutic use of a bacterial protein A61K38/00
• 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: A61K 38/26 Glucagons
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/19 lyophilised , i.e. freeze-dried, solutions or dispersions lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/12 Antidiarrhoeals
• CPC Class Codes: A61P 1/14 Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• 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 31/04 Antibacterial agents
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 39/00 General protective or antinoxious agents
• CPC Class Codes: A61P 39/02 Antidotes
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/00 : Drugs for disorders of the endocrine system
• CPC Class Codes: C07K 14/605 : Glucagons
• CPC Class Codes: C12N 2710/10043 : viral genome or elements thereof as genetic vector
• CPC Class Codes: C12N 2710/20043 : viral genome or elements thereof as genetic vector
• CPC Class Codes: C12N 2710/22043 : viral genome or elements thereof as genetic vector
• CPC Class Codes: C12N 2760/20243 : viral genome or elements thereof as genetic vector
• CPC Class Codes: C12N 7/00 : Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00

Abstract

GLP-2 analogs are disclosed which comprise one of more substitutions as compared to [hGly2]GLP-2 and which improved biological activity in vivo and/or improved chemical stability, e.g., as assessed in in vitro stability assays. More particularly, preferred GLP-2 analogs disclosed herein comprise substitutions at one or more of positions 8, 16, 24 and/or 28 of the wild-type GLP-2 sequence, optionally in combination with further substitutions at position 2 (as mentioned in the introduction) and one or more of positions 3, 5, 7, 10 and 11, and/or a deletion of one or more of amino acids 31 to 33 and/or the addition of a N-terminal or C-terminal stabilizing peptide sequence. The analogs are particularly useful for the prophylaxis or treatment of stomach and bowel-related disorders and for ameliorating side effects of chemotherapy. Also disclosed are methods and kits for selecting a patient from populations suited for treatment with GLP-2 analogs.

Claims

1. A method of treating a patient having a stomach or bowel-related disorder, said method comprising administering an effective amount of a glucagon-like peptide-2 (GLP-2) analog to said patient, wherein said analog is selected from the group consisting of:

2. The method according to claim 1, wherein the GLP-2 analogue is selected from the group consisting of:

3. The method according to claim 1, wherein the GLP-2 analogue is selected from the group consisting of:

4. The method according to claim 1, wherein the GLP-2 analogue is

5. A method of treating a patient having a stomach or bowel-related disorder, said method comprising administering an effective amount of a glucagon-like peptide-2 (GLP-2) analogue to said patient, wherein the GLP-2 analogue is selected from the group consisting of:

6. A method of treating a patient having a stomach or bowel-related disorder, said method comprising administering an effective amount of a glucagon-like peptide-2 GLP-2 analog to said patient, wherein said analog is selected from the group consisting of:

7. The method of claim 6, wherein said stomach or bowel-related disorder is ulcers.

8. The method of claim 6, wherein said stomach or bowel-related disorder is a digestion disorder.

9. The method of claim 6, wherein said stomach or bowel-related disorder is a malabsorption syndrome.

10. The method of claim 6, wherein said stomach or bowel-related disorder is a cul-de-sac syndrome.

11. The method of claim 6, wherein said stomach or bowel-related disorder is celiac sprue.

12. The method of claim 6, wherein said stomach or bowel-related disorder is tropical sprue.

13. The method of claim 6, wherein said stomach or bowel-related disorder is hypogammaglobulinemic sprue.

14. The method of claim 6, wherein said stomach or bowel-related disorder is enteritis or regional enteritis (Crohn'"'"'s disease).

15. The method of claim 6, wherein said stomach or bowel-related disorder is ulcerative colitis.

16. The method of claim 6, wherein said stomach or bowel-related disorder is small intestine damage.

17. The method of claim 16, wherein said stomach or bowel-related disorder is small intestinal damage due to toxic or other chemotherapeutic agents.

18. The method of claim 6, wherein said stomach or bowel-related disorder is short bowel syndrome.

19. A method of treating a patient having short-gut syndrome, said method comprising administering an effective amount of a glucagon-like peptide-2 (GLP-2) analog to said patient, wherein said analog is selected from the group consisting of:

20. A method of treating a patient having a stomach or bowel-related disorder, said method comprising administering an effective amount of a glucagon-like peptide-2 (GLP-2) analog to said patient, wherein said analog is selected from the group consisting of: