Orally active peptides that prevent cell damage and death

• US 8,017,578 B2
• Filed: 04/14/2008
• Issued: 09/13/2011
• Est. Priority Date: 08/18/1999
• Status: Expired due to Fees

• Current Assignee: Ramot at Tel Aviv University Limited (Tel Aviv University), United States Department Of Health And Human Services
• Original Assignee: Ramot at Tel Aviv University Limited (Tel Aviv University), United States Department Of Health And Human Services
• Inventors: Giladi, Eliezer, Pinhasov, Albert, Brenneman, Douglas, Spong, Catherine Y., Gozes, Illana
• Primary Examiner(s): HAYES, ROBERT CLINTON
• Application Number:
  US12/102,760
• Publication Number:
  US 20080194488A1
• Time in Patent Office: 1,247 Days
• Field of Search: None
• US Class Current: 514/8.3
• CPC Class Codes: A61K 38/04 Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof enzyme inhibitors A61K38/005; gastrins A61K38/2207, somatostatins A61K38/31, melanotropins A61K38/34 ; protease inhibitors A61K38/55
• CPC Class Codes: A61K 38/185 Nerve growth factor [NGF]; Brain derived neurotrophic factor [BDNF]; Ciliary neurotrophic factor [CNTF]; Glial derived neurotrophic factor [GDNF]; Neurotrophins, e.g. NT-3

Abstract

This invention provides an ADNF polypeptide comprising an active core site, the active core site comprising at least one D-amino acid. The invention also provides a pharmaceutical composition comprising an ADNF polypeptide comprising an active core site, the active core site comprising at least one D-amino acid. In particular, the pharmaceutical composition of the invention is orally active. The invention further provides methods for reducing neuronal cell death, methods for reducing oxidative stress, and methods for reducing a condition associated with fetal alcohol syndrome using the ADNF polypeptides and the pharmaceutical compositions of the invention.

Claims

1. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and an Activity Dependent Neurotrophic Factor (ADNF) polypeptide, wherein the ADNF polypeptide is an ADNF III polypeptide comprising an active core site having the amino acid sequence of Asn-Ala-Pro-Val-Ser-Ile-Pro-Gln (SEQ ID NO:

2), wherein every amino acid in the active core site is a D-amino acid, and wherein the ADNF III polypeptide inhibits neuronal cell death in cell culture.

2. The pharmaceutical composition of claim 1, wherein the ADNF III polypeptide consists of Asn-Ala-Pro-Val-Ser-Ile-Pro-Gln (SEQ ID NO:

2).

3. The pharmaceutical composition of claim 1, wherein the composition is formulated for intranasal, intraperitoneal, subcutaneous, gavage, sublingual, intravenous, or oral administration.

4. The pharmaceutical composition of claim 3, wherein the composition is formulated for oral administration.

5. An Activity Dependent Neurotrophic Factor (ADNF) III polypeptide comprising an active core site having the amino acid sequence of Asn-Ala-Pro-Val-Ser-Ile-Pro-Gln (SEQ ID NO:

2), wherein every amino acid in the active core site is a D-amino acid, and wherein the ADNF III polypeptide inhibits neuronal cell death in cell culture.

6. The ADNF III polypeptide of claim 5, wherein the ADNF III polypeptide consists of Asn-Ala-Pro-Val-Ser-Ile-Pro-Gln (SEQ ID NO:

2).