Treatment and delay of onset of synucleinopathic and amyloidogenic disease

• US 7,919,088 B2
• Filed: 08/20/2007
• Issued: 04/05/2011
• Est. Priority Date: 10/31/2003
• Status: Active Grant

• Current Assignee: Prothena Biosciences Limited, Regents of the University of California (University of California)
• Original Assignee: Elan Pharmaceuticals Incorporated (Perrigo Company PLC), Regents of the University of California (University of California)
• Inventors: Rockenstein, Edward, Masliah, Eliezar, Games, Kate Dora, Buttini, Manuel J., Chilcote, Tamie J., Schenk, Dale B.
• Primary Examiner(s): Kolker; Daniel E
• Application Number:
  US11/842,054
• Publication Number:
  US 20080175838A1
• Time in Patent Office: 1,324 Days
• Field of Search: None
• US Class Current: 424/133.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 2317/34 Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues

Abstract

The invention provides improved agents and methods for treatment of diseases associated with synucleinopathic diseases, including Lewy bodies of alpha-synuclein in the brain of a patient. Such methods entail administering agents that induce a beneficial immunogenic response against the Lewy body. The methods are particularly useful for prophylactic and therapeutic treatment of Parkinson'"'"'s disease.

Claims

1. A method of reducing the risk of, lessening the severity of, delaying the outset of or treating a disease characterized by Lewy bodies or alpha-synuclein aggregation in the brain, the method comprising administering to a patient having or at risk of the disease an effective regime of an antibody that comprises complementarity determining regions (CDRs) of monoclonal antibody 8A5 deposited at American Type Culture Collection PTA-6909, wherein the antibody specifically binds to intact human alpha-synuclein.

2. The method of claim 1, wherein the antibody is a humanized or chimeric version of mouse monoclonal antibody 8A5 deposited at American Type Culture Collection PTA-6909.

3. The method of claim 1, wherein the antibody is monoclonal antibody 8A5 deposited as ATCC accession number PTA-6909.

4. The method of claim 1, wherein the disease is Parkinson'"'"'s disease.

5. The method of claim 1, wherein the antibody is an antibody of human IgG1 isotype.

6. The method of claim 1, wherein the antibody is administered with a pharmaceutical carrier as a pharmaceutical composition.

7. The method of claim 6, wherein the antibody is administered at a dosage of 0.0001 to 100 mg antibody/kg body weight.

8. The method of claim 6, wherein the antibody is administered in multiple dosages over at least six months.

9. The method of claim 6, wherein the antibody is administered intraperitoneally, orally, subcutaneously, intracranially, intramuscularly, topically, intranasally or intravenously.

10. A method of reducing the risk of, lessening the severity of, delaying the outset of or treating a disease characterized by Lewy bodies or alpha-synuclein aggregation in the brain, the method comprising administering to a patient having or at risk of the disease an effective regime of a humanized or chimeric version of an antibody produced from the cell line JH4.8A5.25.7.36 deposited at American Type Culture Collection PTA-6909, wherein the antibody specifically binds to intact human alpha-synuclein.

11. The method of claim 10, wherein the disease is Parkinson'"'"'s disease.

12. The method of claim 10, wherein the antibody is administered with a pharmaceutical carrier as a pharmaceutical composition.

13. The method of claim 10, wherein the antibody is administered at a dosage of 0.0001 to 100 mg antibody/kg body weight.

14. The method of claim 10, wherein the antibody is administered in multiple dosages over at least six months.

15. The method of claim 10, wherein the antibody is administered intraperitoneally, orally, subcutaneously, intracranially, intramuscularly, topically, intranasally or intravenously.