Adenovirus 36 E4 orf 1 gene and protein and their uses

• US 8,008,436 B2
• Filed: 11/30/2006
• Issued: 08/30/2011
• Est. Priority Date: 11/30/2005
• Status: Active Grant

• Current Assignee: Board of Supervisors of Louisiana State University Agricultural & Mechanical College (Louisiana State University System), Wayne State University
• Original Assignee: Board of SUP of LSU and AGR & Mechanical College, Wayne State University
• Inventors: Dhurandhar, Nikhil V., Wang, Zhong Q., Holland, Thomas C.
• Primary Examiner(s): Li; Bao
• Application Number:
  US12/095,441
• Publication Number:
  US 20090264356A1
• Time in Patent Office: 1,734 Days
• Field of Search: None
• US Class Current: 530/350
• 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: A61K 48/005 characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 5/50 for increasing or potentiating the activity of insulin
• CPC Class Codes: C07K 14/005 from viruses
• CPC Class Codes: C12N 2710/10322 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2710/10332 Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent

Abstract

Expression of the E4 orf 1 gene of Ad-36 alone has been discovered to be responsible for the increased insulin sensitivity observed in Ad-36 infected animals, including increased adipogenesis. Ad-36 E4 orf 1 protein can be used to increase insulin sensitivity and ameliorate diabetes. Additionally, drugs that mimic the action of Ad-36 E4 orf 1 protein could be found. Ad-36 E4 orf 1 could also be used to increase fat cells in lipodystrophy. We have also discovered that Ad-36 infection in human skeletal muscle cells increased differentiation and insulin independent glucose uptake. It is expected that infection with Ad-36 E4 orf 1 gene will also cause these effects.

Claims

1. An isolated protein, Adenovirus-36 E4 orf 1, whose amino acid sequence comprises SEQ ID NO:

2.

2. The protein recited in claim 1, wherein the amino acid sequence of said protein is SEQ ID NO:

2.

3. A pharmaceutical composition comprising the protein of claim 1, additional comprising a pharmaceutical and a pharmaceutically acceptable carrier.

4. A method of treating or ameliorating one or more symptoms of a disease in a mammalian patient wherein the disease is chosen from the group consisting of lipodystrophy, diabetes, and insulin resistance, said method comprising administering to the patient a therapeutically effective amount of Adenovirus-36 E4 orf 1 protein whose amino acid sequence comprises SEQ ID NO:

2, wherein the patient'"'"'s symptoms improve following said administering.

5. A method as in claim 4, wherein the disease is insulin resistance, and wherein the patient'"'"'s insulin sensitivity increases following said administering.

6. A method as in claim 4, wherein the disease is lipodystrophy and wherein the number of adipose tissue cells in the patient increases following said administering.

7. A method as in claim 4, wherein the disease is diabetes and the symptom is a high concentration of serum glucose, and wherein the concentration of serum glucose decreases following said administering.

8. The method of claim 4, wherein the amino acid sequence of the Adenovirus-36 E4 orf 1 protein is SEQ ID NO:

2.

9. The method of claim 4, wherein a pharmaceutical composition comprising the Adenovirus-36 E4 orf 1 protein additionally comprises a pharmaceutical and a pharmaceutically acceptable carrier are administered to the patient.