Glucagon-like-peptide-2 (GLP-2) analogues

• US 9,969,787 B2
• Filed: 08/16/2016
• Issued: 05/15/2018
• Est. Priority Date: 05/03/2012
• Status: Active Grant

• Current Assignee: Zealand Pharma A/S
• Original Assignee: Zealand Pharma A/S
• Inventors: Just, Rasmus, Bovbjerg, Kirsten Lindegaard, Riber, Ditte, Russell, Wayne Shaun
• Primary Examiner(s): LIEB, JEANETTE M
• Application Number:
  US15/238,126
• Publication Number:
  US 20160355563A1
• Time in Patent Office: 637 Days
• Field of Search: None
• CPC Class Codes: A61K 35/22 Urine; Urinary tract, e.g. kidney or bladder; Intraglomerular mesangial cells; Renal mesenchymal cells; Adrenal gland
• CPC Class Codes: A61K 35/48 Reproductive organs
• CPC Class Codes: A61K 35/54 Ovaries; Ova; Ovules; Embryos; Foetal cells; Germ cells
• CPC Class Codes: A61K 35/63 Arthropods aquatic crustaceans A61K35/612
• CPC Class Codes: A61K 35/64 Insects, e.g. bees, wasps or fleas
• CPC Class Codes: A61K 38/26 Glucagons
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• 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 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• 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 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 : Antihypertensives
• CPC Class Codes: C07K 14/605 : Glucagons

Abstract

GLP-2 analogs are disclosed which comprise one of more substitutions as compared to h[Gly2]GLP-2 and which may have the property of an altered GLP-1 activity, and their medical use. The analogs are particularly useful for the prophylaxis treatment or ameliorating of the gastro-intestinal associated side effects of diabetes.

Claims

1. The compound:

Hy-HGDGSFSSELATILDGQAARDFIAWLIQTKITD-OH or a pharmaceutically acceptable salt thereof.

2. A pharmaceutical composition comprising the compound of claim 1 in admixture with a carrier.

3. A method of treating or preventing low grade inflammation, said method comprising administering the compound of claim 1.

4. The method of claim 3, wherein said low grade inflammation is related to diabetes.

5. The method of claim 4, wherein the low grade inflammation related to diabetes is associated with a condition selected from the group consisting of:

metabolic syndrome;

obesity (e.g. abdominal obesity);

diabetes;

cardiovascular diseases;

gastrointestinal inflammation;

depression;

Alzheimer'"'"'s disease;

arthritis;

hypertension;

dyslipidaemia;

stroke;

gastrointestinal disorders in the upper gastrointestinal tract of the esophagus, the stomach, duodenum, the small intestine, colon, and rectum;

ulcers of any aetiology;

digestion disorders;

malabsorption syndromes;

short-bowel syndrome;

cul-de-sac syndrome;

inflammatory bowel disease;

celiac sprue;

tropical sprue;

hypogammaglobulinemic sprue; and

chemotherapy and/or radiation therapy induced mucositis; and

diarrhea.

6. A nucleic acid molecule comprising a nucleic acid sequence encoding the compound of claim 1.

7. An expression vector comprising the nucleic acid sequence of claim 6, in combination with control sequences to direct its expression.

8. A host cell transformed by the expression vector of claim 7.

9. A method of producing the compound of claim 1, the method comprising culturing a host cell transformed by an expression vector under conditions suitable for expressing the compound and purifying the compound thus produced, wherein said expression vector comprises a nucleic acid sequence encoding the compound of claim 1 and control sequences to direct its expression.

10. A method of treating a gastrointestinal related disorder in a patient in need thereof, said method comprising administering an effective amount of the compound of claim 1.

11. The method of claim 10, wherein the gastrointestinal related disorder is low grade inflammation associated with a condition selected from the group consisting of metabolic syndrome;

obesity (e.g. abdominal obesity);

diabetes;

cardiovascular diseases;

gastrointestinal inflammation;

depression;

Alzheimer'"'"'s disease;

arthritis;

hypertension;

dyslipidaemia;

stroke;

gastrointestinal disorders in the upper gastrointestinal tract of the esophagus, the stomach, duodenum, the small intestine, colon, and rectum;

ulcers of any aetiology;

digestion disorders;

malabsorption syndromes;

short-bowel syndrome;

cul-de-sac syndrome;

inflammatory bowel disease;

celiac sprue;

tropical sprue;

hypogammaglobulinemic sprue; and

chemotherapy and/or radiation therapy induced mucositis; and

diarrhea.

12. A therapeutic kit comprising a cancer chemotherapy drug and the compound of claim 1, optionally in combination with a pharmaceutically acceptable carrier.