Prevention and treatment of synucleinopathic and amyloidogenic disease

• US 8,147,833 B2
• Filed: 02/22/2008
• Issued: 04/03/2012
• Est. Priority Date: 02/23/2007
• Status: Active Grant

• Current Assignee: Prothena Biosciences Limited, Regents of the University of California (University of California)
• Original Assignee: Neotope Biosciences Limited (Prothena Corp. Plc), Regents of the University of California (University of California)
• Inventors: Schenk, Dale B., Masliah, Eliezer, Buttini, Manuel J., Chilcote, Tamie J., Rockenstein, Edward, Games, Kate Dora
• Primary Examiner(s): Kolker, Daniel E
• Application Number:
  US12/528,439
• Publication Number:
  US 20100086545A1
• Time in Patent Office: 1,502 Days
• Field of Search: None
• US Class Current: 424/133.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/55566 Emulsions, e.g. Freund's adjuvant, MF59
• CPC Class Codes: A61K 2039/575 humoral response
• CPC Class Codes: A61K 39/0007 Nervous system antigens; Prions
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• 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: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• 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
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

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 treating, reducing the risk of, lessening the severity of, or delaying the outset of 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 specifically binds to human alpha-synuclein (SEQ ID:

1), wherein the antibody is 1H7 (ATCC accession number PTA-8220) or a humanized or chimeric form thereof.

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

3. The method of claim 1, wherein the antibody has the CDRs of antibody 1H7 as defined by Kabat.

4. The method of claim 1, wherein the antibody has the CDRs of antibody 1H7 as defined by Chothia.