Glucagon analogues

• US 10,253,081 B2
• Filed: 05/18/2018
• Issued: 04/09/2019
• Est. Priority Date: 09/17/2012
• Status: Active Grant

• Current Assignee: Zealand Pharma A/S
• Original Assignee: Zealand Pharma A/S
• Inventors: Tolborg, Jakob Lind, Fosgerau, Keld, Norregaard, Pia, Just, Rasmus, Riber, Ditte, Hamprecht, Dieter Wolfgang, Augustin, Robert, Thomas, Leo, Rist, Wolfgang
• Primary Examiner(s): Heard, Thomas S
• Application Number:
  US15/983,822
• Publication Number:
  US 20190055296A1
• Time in Patent Office: 326 Days
• Field of Search: None
• 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 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• 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 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 3/08 for glucose homeostasis pancreatic hormones A61P5/48
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/10 Antioedematous agents; Diuretics
• 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

The invention provides materials and methods for the treatment of obesity and excess weight, diabetes, and other associated metabolic disorders. In particular, the invention provides novel glucagon analog peptides effective in such methods. The peptides may mediate their effect by having increased selectivity for the GLP-1 receptor as compared to human glucagon.

Claims

1. A compound having the formula:

R¹—

X—

OH

wherein

R¹ is H, C_1-4 alkyl, acetyl, formyl, benzoyl or trifluoroacetyl;

and X is a peptide which has the formula;

7. A compound according to claim 1 wherein one or more of the amino acid side chains in the peptide X or Z is conjugated to a lipophilic substituent.

8. A compound according to claim 7 wherein peptide X has the formula:

9. A compound according to claim 8 having the formula:

2. A compound having the formula:

R¹—

X—

Z—

R²

wherein

R¹ is H, C_1-4 alkyl, acetyl, formyl, benzoyl or trifluoroacetyl;

R² is OH or NH₂;

X is a peptide of SEQ ID NO;

15;

3. A compound according to claim 2 wherein the residue at position 20 is His.

4. A compound according to claim 2 the formula:

R¹—

X—

Z—

R²

wherein

R¹ is H, C_1-4 alkyl, acetyl, formyl, benzoyl or trifluoroacetyl;

R² is OH or NH₂;

X is a peptide of SEQ ID NO;

15;

10. A compound according claim 2 wherein one or more of the amino acid side chains in the peptide X or Z is conjugated to a lipophilic substituent.

11. A compound according to claim 10 wherein peptide X has the formula:

12. A compound according to claim 11 the formula:

5. A compound having the formula:

R¹—

X—

Z—

R²

wherein

R¹ is H, C_1-4 alkyl, acetyl, formyl, benzoyl or trifluoroacetyl;

R² is OH or NH₂;

X is a peptide of SEQ ID NO;

16;

6. A compound according to claim 5 the formula:

R¹—

X—

Z—

R²

wherein

R¹ is H, C_1-4 alkyl, acetyl, formyl, benzoyl or trifluoroacetyl;

R² is OH or NH₂;

X is a peptide of SEQ ID NO;

16;

13. A compound according claim 5 wherein one or more of the amino acid side chains in the peptide X or Z is conjugated to a lipophilic substituent.

14. A compound according to claim 13 wherein peptide X has the formula:

15. A compound according to claim 14 having the formula: