Generation of new pancreatic beta cells

• US 9,511,110 B2
• Filed: 10/26/2012
• Issued: 12/06/2016
• Est. Priority Date: 09/27/2012
• Status: Active Grant

• Current Assignee: Claresa Levetan
• Original Assignee: Perle Bioscience, Inc.
• Inventors: Levetan, Claresa
• Primary Examiner(s): Ewoldt, Gerald R
• Application Number:
  US13/662,245
• Publication Number:
  US 20140120097A1
• Time in Patent Office: 1,502 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 38/08 Peptides having 5 to 11 amino acids A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• 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 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 16/2839 against the integrin superfamily
• CPC Class Codes: C07K 2317/34 Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: C07K 2317/75 Agonist effect on antigen

Abstract

The present invention relates to novel therapies for treatment of new and existing type 1 and type 2 diabetes, PreDiabetes, Latent Autoimmune Diabetes of Adulthood, and diseases of insulin deficiency, beta cell deficiency, insulin resistance and impaired glucose metabolism. In particular, the present invention identifies common peptides within the human Reg1a, Reg1b, Reg3a and Reg4, as signaling peptides for beta cell generation acting through the human Reg Receptor on the surface of human pancreatic extra-islet tissue. This invention identifies a specific binding region of the Reg Receptor from which peptidomimetics and stimulating antibodies have been developed for the generation of new beta cells which may be administered directly to patients with said conditions including type 1 diabetes, type 2 diabetes, PreDiabetes and other conditions of beta cell deficiency, and provides specific methodology for protecting new beta cells generated for usage in type 1 diabetes and Latent Autoimmune Diabetes of Adulthood. This invention also provides for ex-vivo generation and delivery of beta cells utilizing the inventions described within.

Claims

1. A method of treating type 1 and 2 diabetes, comprising the step of:

administering to a subject a therapeutically effective amount of a peptide that has Reg receptor binding activity, wherein the peptide consists of an amino acid sequence selected from the group consisting of SEQ ID NO;

1, SEQ ID NO;

4, SEQ ID NO;

7, SEQ ID NO;

8, and SEQ ID NO;

14.

2. The method of claim 1, wherein an immune modulator is administered before and/or in parallel with the administration of the therapeutically effective amount of the peptide that has Reg receptor binding activity.

3. The method of claim 2, wherein the immune modulator is administered at repeat dosages for the protection of newly-formed beta cells.

4. The method of claim 2, wherein the immune modulator is a general immunosuppressant agent or an antibody targeted to lymphocytes.

5. The method of claim 1, wherein a period of glucose control is optimized before the administration of the therapeutically effective amount of the peptide that has Reg receptor binding activity;

wherein the glucose control is optimized for glucose levels of between 100 to 200 mg/dl or the glucose control is optimized to prevent glucose levels from falling below 70 mg/dl.

6. The method of claim 5, wherein the period of glucose control is at least 4 weeks.

7. The method of claim 1, wherein the subject'"'"'s insulin dose is decreased based on glucose levels to prevent an episode of hypoglycemia.

8. The method of claim 1, wherein the peptide that has Reg receptor binding activity is administered through oral, intravenous, intra-arterial, or subcutaneous delivery.

9. The method of claim 1, wherein the peptide that has Reg receptor binding activity is administered directly to the pancreas or the liver.

10. The method of claim 1, wherein the peptide that has Reg receptor binding activity is administered in combination with another diabetic agent.

11. The method of claim 10, wherein the other diabetic agent is a form of insulin, liraglutide, exenatide, sitagliptin, saxagliptin, linagliptin, pramlintide, acarbose, orlistat, colesevelam, bromocriptine, biguanide, metformin, dapagliflozin, canagliflozin, a sulfonylurea, a meglitinide, a GLP-1 receptor analog, a DPP-4 inhibitor, a thiazolidinedione, an SGLT2 inhibitor, an anti-inflammatory agent, or vitamin D.

12. The method of claim 10, wherein administration of the other diabetic agent is tapered off or reduced based on daily glucose values.

13. The method of claim 12, wherein the other diabetic agent is insulin and is reduced by about 0.5-2.0% per day.

14. The method of claim 1, wherein the subject is diabetes-drug naï

ve.

15. The method of claim 1, wherein the peptide is administered at intervals to maintain a minimum number of beta cells for normal glucose metabolism.