Spheron component peptides and pharmaceutical compositions

• US 7,514,407 B2
• Filed: 05/23/2003
• Issued: 04/07/2009
• Est. Priority Date: 03/04/2002
• Status: Active Grant

• Current Assignee: Nymox Corporation
• Original Assignee: Nymox Corporation
• Inventors: Averback, Paul
• Primary Examiner(s): Kolker; Daniel E.
• Application Number:
  US10/444,070
• Publication Number:
  US 20040029809A1
• Time in Patent Office: 2,146 Days
• Field of Search: None
• US Class Current: 514/1.1
• CPC Class Codes: A01K 2217/05 Animals comprising random inserted nucleic acids (transgenic)
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/4702 Regulators; Modulating activity
• CPC Class Codes: C07K 14/4711 Alzheimer's disease; Amyloid plaque core protein
• CPC Class Codes: C07K 7/06 having 5 to 11 amino acids
• CPC Class Codes: C07K 7/08 having 12 to 20 amino acids gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68

Abstract

The present invention relates to racemized proteins and racemized protein components of spherons that are useful for identifying compounds capable of preventing and/or ameliorating symptoms of Alzheimer'"'"'s Disease and/or dementia associated with cerebral amyloidosis. The invention also relates to the compounds identified by the methods, and methods of treating and/or ameliorating symptoms of Alzheimer'"'"'s Disease and/or dementia associated with cerebral amyloidosis. The invention also relates to methods of making an Alzheimer'"'"'s Disease or dementia associated with cerebral amyloidosis animal model or test animal, the animal model produced therefrom, and to a method of using the animal model to screen for effective therapies.

Claims

1. An isolated spheron component peptide consisting of the amino acid sequence of GEAAGAVQELAR (SEQ ID NO:

1) and up to 25 additional amino acids, wherein the spheron component peptide is cytotoxic.

2. The spheron component peptide of claim 1, wherein at least one of the amino acid residues of the spheron component peptide is aspartic acid or serine and wherein at least one of the aspartic acid or serine has been racemized from an L stereoisomer form to a D stereoisomer form.

3. The spheron component peptide of claim 1, wherein at least one peptide bond is substituted with a non-peptide bond.

4. The spheron component peptide of claim 1, wherein all of the peptide bonds have been substituted with non-peptide bonds.

5. A pharmaceutical composition comprising the spheron component peptide of claim 1 and a carrier thereof.

6. A pharmaceutical composition comprising the spheron component peptide of claim 3 and a carrier thereof.

7. A pharmaceutical composition comprising the spheron component peptide of claim 4 and a carrier thereof.

8. A spheron component peptide mimetic consisting of the amino acid sequence of GEAAGAVQELAR (SEQ ID NO:

1) and up to 25 additional amino acids, wherein at least one peptide bond is substituted with a non-peptide bond, and wherein the spheron component peptide mimetic is cytotoxic.

9. The mimetic of claim 8, wherein at least one of the amino acid residues of the mimetic is aspartic acid or serine and wherein at least one of the aspartic acid or serine has been racemized from an L stereoisomer form to a D stereoisomer form.

10. The mimetic of claim 8, wherein all of the peptide bonds have been substituted with a non-peptide bonds.

11. A pharmaceutical composition comprising the spheron component peptide mimetic of claim 8 and a carrier thereof.

12. A pharmaceutical composition comprising the spheron component peptide mimetic of claim 9 and a carrier thereof.