Long lasting insulinotropic peptides

• US 6,329,336 B1
• Filed: 09/05/2000
• Issued: 12/11/2001
• Est. Priority Date: 05/17/1999
• Status: Expired due to Fees

• Current Assignee: ConjuChem LLC (Colabor Group, Inc.)
• Original Assignee: ConjuChem, Inc. (Colabor Group, Inc.)
• Inventors: Bridon, Dominique P., Ezrin, Alan M., St. Pierre, Serge, Leblanc, Anouk, Holmes, Darren L., LʼArcheveque, Benoit
• Primary Examiner(s): Horlick, Kenneth R.
• Assistant Examiner(s): Strzelecka, Teresa
• Application Number:
  US09/623,618
• Time in Patent Office: 462 Days
• Field of Search: 514/12, 514/2
• US Class Current: 514/5.9
• 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: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 25/22 Anxiolytics
• 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 3/04 Anorexiants; Antiobesity agents
• 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 35/00 Antineoplastic agents
• CPC Class Codes: A61P 41/00 Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
• CPC Class Codes: C07K 14/005 from viruses
• CPC Class Codes: C07K 14/605 Glucagons
• CPC Class Codes: C12N 2740/16122 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes

Abstract

Modified insulinotropic peptides are disclosed. The modified insulinotropic peptides are capable of forming a peptidase stabilized insulinotropic peptide. The modified insulinotropic peptides are capable of forming covalent bonds with one or more blood components to form a conjugate. The conjugates may be formed in vivo or ex vivo. The modified peptides are administered to treat humans with diabetes and other related diseases.

Claims

1. An insulinotropic peptide modified with a reactive group which reacts with amino groups, hydroxyl groups or thiol groups on blood components to form a stable covalent bond, the insulinotropic peptide being selected from the group consisting of SEQ ID NO:

16, SEQ ID NO;

17, SEQ ID NO;

18, SEQ ID NO 19, SEQ ID NO;

20 and SEQ ID NO;

21.

5. A method for treating diabetes in a patient, comprising administering to the patient an effective amount of a modified insulinotropic peptide as claimed in claim 1.

7. A method for enhancing the expression of insulin in a patient, comprising administering to the patient an effective amount of a modified insulinotropic peptide as claimed in claim 1.

9. A method for extending the in vivo half-life of an insulinotropic peptide as claimed in claim 1, the method comprising coupling to the peptide said reactive group which is capable of forming a covalent bond with a blood component in vivo, thereby forming a modified insulinotropic peptide having an in vivo half-life longer than the in vivo half-life of the insulinotropic peptide.

10. A method as claimed in claim 9 wherein the reactive group is a maleimide and the blood component is serum albumin.

11. A conjugate comprising a modified insulinotropic peptide as claimed in claim 1 covalently bonded ex vivo to a blood component.

12. A conjugate as claimed in claim 11 wherein the blood component is serum albumin.

2. A composition comprising a derivative of an insulinotropic peptide, said derivative comprising a reactive group which reacts with amino groups, hydroxyl groups or thiol groups on blood components to form stable covalent bonds wherein said reactive group is selected from the group consisting of succinimidyl and maleimido groups for use in a method of treating diabetes in a human, and wherein the insulinotropic peptide is selected from the group consisting of SEQ ID NO:

16, SEQ ID NO;

17, SEQ ID NO;

18, SEQ ID NO;

19, SEQ ID NO;

20, SEQ ID NO;

21 and SEQ ID NO;

22.

3. A derivative of an insulinotropic peptide, said derivative comprising a maleimido group which reacts with a thiol group on human serum albumin to form a covalent bond, the insulinotropic peptide being selected from the group consisting of SEQ ID NO:

16, SEQ ID NO;

17, SEQ ID NO;

18, SEQ ID NO;

19, SEQ ID NO;

20, SEQ ID NO;

21 and SEQ ID NO;

22.

6. A method for treating diabetes in a patient, comprising administering to the patient an effective amount of a modified insulinotropic peptide as claimed in claim 3.

8. A method for enhancing the expression of insulin in a patient, comprising administering to the patient an effective amount of a modified insulinotropic peptide as claimed in claim 3.

13. A conjugate comprising a modified insulinotropic peptide as claimed in claim 3 covalently bonded ex vivo to a blood component.

14. A conjugate as claimed in claim 13 wherein the blood component is serum albumin.

4. A composition comprising a derivative of an insulinotropic peptide, said derivative comprising a maleimido group which reacts with a thiol group on human serum albumin to form a covalent bond for use in a method of treating diabetes in a human, the insulinotropic peptide being selected from the group consisting of SEQ ID NO:

16 SEQ ID NO;

17, SEQ ID NO;

18, SEQ ID NO;

19, SEQ ID NO;

20, SEQ ID NO;

21 and SEQ ID NO;

22.