US 9,580,487 B2 · Method of treating stomach or bowel-related disorders by administering glucagon-like-peptide-2 (GLP-2) analogues

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.

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:

(SEQ ID NO:
1) (Compound 1809)
H-HGEGTFSDELATILDALAARDFIAWLIATKITDKKKKKK-NH2,
(SEQ ID NO:
2) (Compound 1810)
H-HGEGTFSDELATILDALAARIFIAWLIATKKKKKKK-NH2,
(SEQ ID NO:
3) (Compound 1811)
H-HGDGSPSDELATILDALAARDFIAWLIATKITD-NH2,
(SEQ ID NO:
4) (Compound 1812)
H-HGEGSFSDELATILDNLAARDFIAWLIQTKITD-NH2,
(SEQ ID NO:
5) (Compound 1813)
H-HGDGSFSDELATILDALAARDFIAWLIATKITD-NH2,
(SEQ ID NO:
6) (Compound 1814)
H-HGDGSFSDELATILDNLAARDFIAWLIATKITD-NH2,
(SEQ ID NO:
7) (Compound 1815)
H-HGEGSFSDELATILDALAARDFIAWLIATKITD-NH2,
(SEQ ID NO:
8) (Compound 1818)
H-HGDGSFSSELATILDNLAARDFIAWLIQTKKKKKKK-NH2,
(SEQ ID NO:
9) (Compound 1819)
H-HGDGSFSDELSTILDNLAARDFIAWLIQTKKKKKKK-NH2,
(SEQ ID NO:
10) (Compound 1820)
H-HGDGSFTSELATILDNLAARDFIAWLIQTKKKKKKK-NH2,
(SEQ ID NO:
11) (Compound 1821)
H-HGDGSFSDELKTILDNLAARDFIAWLIQTKKKKKKK-NH2,
(SEQ ID NO:
12) (Compound 1822)
H-HGDGSFTDELKTILDNLAARDFIAWLIQTKKKKKKK-NH2,
(SEQ ID NO:
13) (Compound 1823)
H-HGDGSFTSELKTILDNLAARDFIAWLIQTKKKKKKK-NH2,
(SEQ ID NO:
14) (Compound 1824)
H-HGDGSFTDELATILDNLAARDFIAWLIQTKKKKKKK-NH2,
(SEQ ID NO:
15) (Compound 1825)
H-HGDGSFSSELATILDNLAARDFIAWLIQTK-NH2,
(SEQ ID NO:
17) (Compound 1827)
H-HGDGSFTDELSTILDNLAARDFIAWLIQTKKKKKKK-NH2,
(SEQ ID NO:
18) (Compound 1828)
H-HGDGSFTSELSTILDNLAARDFIAWLIQTKKKKKKK-NH2,
(SEQ ID NO:
19) (Compound 1829)
H-HGDGSFSSELSTILDNLAARDFIAWLIQTKKKKKKK-NH2,
(SEQ ID NO:
20) (Compound 1830)
H-HGDGSFSDELSTILDNLAARDFIAWLIQTK-NH2,
(SEQ ID NO:
21) (Compound 1831)
H-HGDGSFTDELSTILDNLAARDFIAWLIQTK-NH2,
(SEQ ID NO:
22) (Compound 1832)
H-HGDGSFTSELSTILDNLAARDFIAWLIQTK-NH2,
(SEQ ID NO:
23) (Compound 1833)
H-HGDGSFSSELSTILDNLAARDFIAWLIQTK-NH2,
(SEQ ID NO:
24) (Compound 1834)
H-HGDGSFTSELATILDNLAARDFIAWLIQTK-NH2,
(SEQ ID NO:
25) (Compound 1835)
H-HGDGSFSDELKTILDNLAARDFIAWLIQTK-NH2,
(SEQ ID NO:
26) (Compound 1836)
H-HGDGSFTDELKTILDNLAARDFIAWLIQTK-NH2,
(SEQ ID NO:
27) (Compound 1839)
H-HGDGSFSDELATILDNLAARDFIAWLIQTKITDKKKKKK-NH2,
(SEQ ID NO:
28) (Compound 1840)
H-HGDGSFSDELATILDNLAARDFIAWLIQTKITD-NH2,
(SEQ ID NO:
29) (Compound 1841)
H-HGDGSFSDELATILDNLAARDFIAWLIQTK-NH2,
(SEQ ID NO:
30) (Compound 1842)
H-HGDGSFTSELKTILDNLAARDFIAWLIQTK-NH2,
(SEQ ID NO:
31) (Compound 1843)
H-HGDGSFTDELATILDNLAARDFIAWLIQTK-NH2,
(SEQ ID NO:
32) (Compound 1844)
H-HGEGTFSSELSTILDALAARDFIAWLIATKITDKKKKKK-NH2,
(SEQ ID NO:
33) (Compound 1845)
H-HGEGTFSDELSTILDALAARDFIAWLIATKITDKKKKKK-NH2,
(SEQ ID NO:
35) (Compound 1847)
H-HGEGSFSDELSTILDALAARDFIAWLIATKITDKKKKKK-NH2,
(SEQ ID NO:
36) (Compound 1848)
H-HGEGTFSSELATILDALAARDFIAWLIATKITDKKKKKK-NH2,
(SEQ ID NO:
37) (Compound 1849)
H-HGEGSFSSELATILDALAARDFIAWLIATKITDKKKKKK-NH2,
(SEQ ID NO:
38) (Compound 1850)
H-HGEGSFSDELKTILDALAARDFIAWLIATKITDKKKKKK-NH2,
(SEQ ID NO:
39) (Compound 1851)
H-HGEGTFSDELKTILDALAARDFIAWLIATKITDKKKKKK-NH2,
(SEQ ID NO:
40) (Compound 1852)
H-HGEGTFSSELKTILDALAARDFIAWLIATKITDKKKKKK-NH2,
(SEQ ID NO:
41) (Compound 1853)
H-HGEGTFSSELSTILDALAARDFIAWLIATKITD-NH2,
(SEQ ID NO:
42) (Compound 1854)
H-HGEGTFSDELSTILDALAARDFIAWLIATKITD-NH2
(SEQ ID NO:
43) (Compound 1855)
H-HGEGSFSSELSTILDALAARDFIAWLIATKITD-NH2,
(SEQ ID NO:
44) (Compound 1856)
H-HGEGSFSDELSTILDALAARDFIAWLIATKITD-NH2,
(SEQ ID NO:
45) (Compound 1857)
H-HGEGTFSSELATILDALAARDFIAWLIATKITD-NH2,
(SEQ ID NO:
46) (Compound 1858)
H-HGEGSFSSELATILDALAARDFIAWLIATKITD-NH2,
(SEQ ID NO:
47) (Compound 1859)
H-HGEGSFSDELKTILDALAARDFIAWLIATKITD-NH2,
(SEQ ID NO:
48) (Compound 1860)
H-HGEGTFSDELKTILDALAARDFIAWLIATKITD-NH2,
and
(SEQ ID NO:
49) (Compound 1861)
H-HGEGTFSSELKTILDALAARDFIAWLIATKITD-NH2;
or a pharmaceutically acceptable salt thereof.

140 more elements

Facts

Application

14/847,938Filed 8 Sep 2015 · continuation

Priority

4 May 2005

Published

US 2015/0368314 A124 Dec 2015

Granted

28 Feb 2017

Term ends

Not estimatedThe source records don’t support an estimate.

Classification32 codes

C07K 14/605
Hormones: glucagons
A61K 9/0019
Galenical forms characterised by the site of application: injectable compositions; Intramuscular, intravenous, arterial, subcutaneous…
A61K 9/19
Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles: lyophilised , i.e.…
A61K 35/54
Reproductive organs: ovaries; Ova; Ovules; Embryos; Foetal cells; Germ cells

Family

Application60/678,066Us provisional application · filed 4 May 2005

Application11/429,168Parent of this continuation-in-part · filed 4 May 2006

Application11/595,496Parent of this continuation · filed 9 Nov 2006

Application12/643,233Parent of this continuation · filed 21 Dec 2009

Application13/536,377Parent of this continuation · filed 28 Jun 2012

Application14/792,686Parent of this continuation · filed 7 Jul 2015

US 2015/0368314 A1Pre-grant publication · published 24 Dec 2015

US 9,125,882 B2Parent of this continuation

US 8,263,552 B2Parent of this continuation

US 7,745,403 B2Parent of this continuation

US 7,563,770 B2Parent of this continuation-in-part

Application11/595,496Parent of this continuation-in-part

US 2007/0117752 A1Published application

US 2007/0231308 A1Published application

US 2011/0098222 A1Published application

US 2012/0289466 A1Published application

US 9,580,487 B2This patent

From the US filing history. Foreign family members aren’t listed.

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

Life of this patent

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

Life of this patent

Abstract

Claims20