AAV mediated exendin-4 gene transfer to salivary glands to protect subjects from diabetes or obesity

Patent metadata

Field	Value
Publication number	US-9511103-B2
Application number	US-201214112790-A
Country	US
Kind code	B2
Filing date	Apr 19, 2012
Priority date	Apr 20, 2011
Publication date	Dec 6, 2016
Grant date	Dec 6, 2016

Abstract

The invention relates to a gene transfer-based method to protect a subject from diabetes or obesity. The method comprises administering to a salivary gland of the subject an AAV virion comprising an AAV vector that encodes an exendin-4 protein. Also provided are exendin-4 proteins and nucleic acid molecules that encode such exendin-4 proteins. Also provided are AAV vectors and AAV virions that encode an exendin-4 protein. One embodiment is an exendin-4 protein that is a fusion protein comprising an NGF secretory segment joined to the amino terminus of an exendin-4 protein domain.

First claim

What is claimed is:

1. A method to protect a subject from Type II diabetes or obesity, the method comprising administering to a salivary gland of the subject an adeno-associated virus (AAV) virion comprising an AAV vector that encodes an exendin-4 fusion protein comprising a secretory segment joined to an exendin-4 protein.

2. The method of claim 1 , wherein the secretory segment is a nerve growth factor (NGF) secretory segment.

3. The method of claim 2 , wherein the NGF secretory segment is cleavable from the exendin-4 protein by a furin protease.

4. The method of claim 2 , wherein the NGF secretory segment comprises SEQ ID NO:10.

5. The method of claim 1 , wherein the exendin-4 protein comprises the amino acid sequence of SEQ ID NO:8.

6. The method claim 1 , wherein the AAV vector comprises a nucleic acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5 and SEQ ID NO:7.

7. The method of claim 1 , wherein the exendin-4 fusion protein comprises SEQ ID NO:2.

Assignees

• Chiorini John A
• Di Pasquale Giovanni
• Mannucci Edoardo
• Us Health

Inventors

• Chiorini John A
• Di Pasquale Giovanni
• Mannucci Edoardo

Classifications

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P3/04

  Anorexiants; Antiobesity agents · CPC title

• C07K2319/50

  containing protease site · CPC title

• C07K2319/055

  containing a signal for localisation to secretory granules (for exocytosis) · CPC title

• C07K14/57563

  Vasoactive intestinal peptide [VIP]; Related peptides · CPC title