GLUCAGON-LIKE-PEPTIDE-2 (GLP-2) ANALOGUES

• US 20190330295A1
• Filed: 01/03/2019
• Published: 10/31/2019
• Est. Priority Date: 05/04/2005
• Status: Abandoned Application

• Current Assignee: Zealand Pharma A/S
• Original Assignee: Zealand Pharma A/S
• Inventors: LARSEN, Bjarne Due, PETERSEN, Yvette Miata
• Application Number:
  US16/239,225
• Publication Number:
  US 20190330295A1
• Time in Patent Office: Days
• 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 47/183 Amino acids, e.g. glycine, EDTA or aspartame
• 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: C07K 14/605 Glucagons
• CPC Class Codes: C12N 15/09 Recombinant DNA-technology
• CPC Class Codes: C12N 15/63 Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
• 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 5/10 Cells modified by introduction of foreign genetic material
• 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 analogues 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 analogues 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 analogues 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 analogues.

Claims

1-48. -48. (canceled)

49. A method for treating anorexia in a patient in need thereof comprising administering to the patient a pharmaceutical composition formulated for parenteral administration comprising:

(a) the glucagon-like peptide 2 (GLP-2) analogue [Gly2, Glu3, Leu10, Ala11, 24]hGLP-2-NH₂ represented by the sequence;

50. The method of claim 49, wherein the pharmaceutically acceptable carrier further comprises a histidine buffer.

51. A method of producing the GLP-2 analogue [Gly2, Thr7, Leu10, Lys11, Ala24]hGLP-2(1-30)-K6-NH₂ represented by the sequence:

52. The method of claim 51, wherein the host cells are bacterial cells.

53. A therapeutic kit comprising:

(i) a cancer chemotherapy drug, and

(ii) the glucagon-like peptide 2 (GLP-2) analogue [Gly2, Pro6, Leu10, Ala11, 16,24, 28]hGLP-2-NH₂ represented by the sequence;

54. The therapeutic kit of claim 53, wherein the cancer chemotherapy drug is methotrexate.