Active immunization of AScr for prion disorders

• US 6,923,964 B1
• Filed: 06/01/2000
• Issued: 08/02/2005
• Est. Priority Date: 12/02/1997
• Status: Expired due to Term

• Current Assignee: Prothena Biosciences Limited
• Original Assignee: Neuralab Ltd. (Perrigo Company PLC)
• Inventors: Schenk, Dale B.
• Primary Examiner(s): Kemmerer, Elizabeth
• Assistant Examiner(s): NICHOLS, CHRISTOPHER J
• Application Number:
  US09/585,817
• Time in Patent Office: 1,888 Days
• Field of Search: 424/185.1, 514/2, 514/4, 514/12, 530/300, 530/350
• US Class Current: 424/185.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/53 DNA (RNA) vaccination
• CPC Class Codes: A61K 2039/55505 Inorganic adjuvants
• CPC Class Codes: A61K 2039/55555 Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers
• CPC Class Codes: A61K 2039/55566 Emulsions, e.g. Freund's adjuvant, MF59
• CPC Class Codes: A61K 2039/55572 Lipopolysaccharides; Lipid A; Monophosphoryl lipid A
• CPC Class Codes: A61K 2039/55577 Saponins; Quil A; QS21; ISCOMS
• CPC Class Codes: A61K 2039/6037 Bacterial toxins, e.g. diphteria toxoid [DT], tetanus toxoid [TT]
• CPC Class Codes: A61K 2039/605 MHC molecules or ligands thereof
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 38/1709 from mammals
• CPC Class Codes: A61K 38/193 Colony stimulating factors [CSF]
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61K 39/0007 Nervous system antigens; Prions
• CPC Class Codes: C07K 14/4711 Alzheimer's disease; Amyloid plaque core protein
• 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
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: G01N 33/6896 Neurological disorders, e.g. Alzheimer's disease

Abstract

Disclosed are pharmaceutical compositions and methods for preventing or treating a number of amyloid diseases, including Alzheimer'"'"'s disease, prion diseases, familial amyloid neuropathies and the like. The pharmaceutical compositions include immunologically reactive amounts of amyloid fibril components, particularly fibril-forming peptides or proteins. Also disclosed are therapeutic compositions and methods which use immune reagents that react with such fibril components.

Claims

1. A method of treating a prior disorder associated with AScr in a mammalian subject suffering from the disorder, comprising administering to the subject a dosage of an agent effective to produce an immune response comprising antibodies against the agent and an adjuvant that augments the immune response to the agent, and thereby treating the disorder, wherein the agent is PrR or AScr.

2. The method of claim 1, wherein the agent is AScr.

3. The method of claim 1, wherein said agent is PrP.

4. The method of claim 1, wherein said agent is a peptide linked to a carrier molecule.

5. The method of claim 1, wherein said adjuvant is selected from the group consisting of QS21, monophosphoryl lipid, and alum.

6. The method of claim 1, wherein said immune response is characterized by a serum titer of the antibodies of at least 1:

1000 with respect to the agent.

7. The method of claim 6, wherein said serum titer of the antibodies is at least 1:

5000 with respect to the agent .

8. The method of claim 1, wherein said immune response is characterized by a serum titer of the antibodies against the agent corresponding to greater than about four times higher than a serum titer of antibodies measured in a pre-treatment control serum sample.

9. The method of claim 8, wherein said serum titer of the antibodies is measured at a serum dilution of about 1:

100.

10. The method of claim 3, wherein the agent is selected from the following PrP genetic variants:

Leu102, Val167, Asn178, and Lys200.