Ligand/lytic peptide compositions and methods of use

US6635740B1 · kind B1 · utility

Assignee

• BOARD OF SUPERVISORS OF LOUISIANA STATE UNIVERSITY AND AGRICULTURAL AND MECHANICAL COLLEGE · US

Inventors

• Frederick M. Enright · Baton Rouge, US
• Jesse M. Jaynes · Baton Rouge, US
• William Hansel · Baton Rouge, US
• Kenneth L. Koonce · Baton Rouge, US
• Samuel M. McCann · Baton Rouge, US
• Wen H. Yu · Baton Rouge, US
• Patricia A. Melrose · Baton Rouge, US
• Lane D. Foil · Baton Rouge, US
• Philip H. Elzer · Baton Rouge, US

Key dates

• Filing date: Sep 24, 1999
• Grant date: Oct 21, 2003
• Expiry date: Sep 24, 2019

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07K2319/00
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Amphipathic lytic peptides are ideally suited to use in a ligand/cytotoxin combination to specifically inhibit cells that are driven by or are dependent upon a specific ligand interaction; for example, to induce sterility or long-term contraception, or to attack tumor cells, or to selectively lyse virally-infected cells, or to attack lymphocytes responsible for autoimmune diseases. The peptides act directly on cell membranes, and need not be internalized. Administering a combination of gonadotropin-releasing hormone (GnRH) (or a GnRH agonist) and a membrane-active lytic peptide produces long-term contraception or sterilization in animals in vivo. Administering in vivo a combination of a ligand and a membrane-active lytic peptide kills cells with a receptor for the ligand. The compounds are relatively small, and are not antigenic. Lysis of gonadotropes has been observed to be very rapid (on the order of ten minutes.) Lysis of tumor cells is rapid. The two components—the ligand and the lytic peptide—may optionally be administered as a fusion peptide, or they may be administered separately, with the ligand administered slightly before the lytic peptide, to activate cells w…