Generation of new pancreatic beta cells

• US 8,911,776 B2
• Filed: 10/26/2012
• Issued: 12/16/2014
• Est. Priority Date: 09/27/2012
• Status: Active Grant

• Current Assignee: Claresa Levetan
• Original Assignee: Perle Bioscience, Inc.
• Inventors: Levetan, Claresa
• Primary Examiner(s): Skowronek, Karlheinz R
• Assistant Examiner(s): Milton, Schuyler
• Application Number:
  US13/662,209
• Publication Number:
  US 20140120154A1
• Time in Patent Office: 781 Days
• Field of Search: None
• US Class Current: 424/450
• CPC Class Codes: A61K 35/39 Pancreas; Islets of Langerhans Langerhans cells of epidermis A61K35/36
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: C07K 14/435 from animals; from humans
• CPC Class Codes: C07K 14/47 from mammals
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: C12N 2501/998 Proteins not provided for elsewhere
• CPC Class Codes: C12N 5/0676 Pancreatic cells

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. An isolated peptide consisting of an amino acid sequence selected from the group consisting of NVWIGLHDP (SEQ ID NO:

1), VWIGLHDP (SEQ ID NO;

4), and WIGLHDP (SEQ ID NO;

7), wherein the peptide has been modified to increase stability, increase solubility, increase protease resistance, reduce immunogenicity, increase Tmax, or increase bioavailability.

2. The isolated peptide of claim 1, wherein the peptide is blocked with a c-terminal acetyl group and n-terminal amide group.

3. The isolated peptide of claim 1, wherein the peptide includes a cysteine residue added to the n-terminal.

4. The isolated peptide of claim 1, wherein the peptide is modified by cyclization.

5. The isolated peptide of claim 1, wherein the peptide is modified by pegylation.

6. A pharmaceutical formulation comprising the isolated peptide of claim 1.

7. The pharmaceutical formulation of claim 6, wherein the formulation is optimized for oral, intravenous, or subcutaneous delivery.

8. The pharmaceutical formulation of claim 6, that is a unit dose form.

9. The pharmaceutical formulation of claim 6, further comprising one or more other active pharmaceutical ingredients (APIs).

10. The pharmaceutical formulation of claim 9, wherein the API is an agent in a soluble liposome preparation.

11. The pharmaceutical formulation of claim 10, wherein the liposome preparation allows the peptide to be administered subcutaneously, intramuscularly, intravenously, intra-arterially, or orally.

12. The pharmaceutical formulation of claim 10, wherein the formulation is optimized for systemic administration.

13. The pharmaceutical formulation of claim 10, wherein the formulation includes a targeting agent for targeted administration.