Method for treating amyloid disease

• US 8,906,382 B2
• Filed: 07/19/2012
• Issued: 12/09/2014
• Est. Priority Date: 07/19/2011
• Status: Active Grant

• Current Assignee: New York University
• Original Assignee: New York University
• Inventors: Wisniewski, Thomas, Goni, Fernando R.
• Primary Examiner(s): BALLARD, KIMBERLY
• Application Number:
  US13/553,566
• Publication Number:
  US 20130022630A1
• Time in Patent Office: 873 Days
• US Class Current: 424/185.1
• CPC Class Codes: A61K 2039/542 oral/gastrointestinal
• CPC Class Codes: A61K 2039/55 characterised by the host/recipient, e.g. newborn with maternal antibodies
• CPC Class Codes: A61K 2039/555 characterised by a specific combination antigen/adjuvant
• CPC Class Codes: A61K 2039/55516 Proteins; Peptides
• CPC Class Codes: A61K 2039/55544 Bacterial toxins
• CPC Class Codes: A61K 2039/575 humoral response
• CPC Class Codes: A61K 2039/58 raising an immune response against a target which is not the antigen used for immunisation
• CPC Class Codes: A61K 38/18 Growth factors; Growth regulators
• CPC Class Codes: A61K 39/0005 Vertebrate antigens from snakes A61K39/38
• CPC Class Codes: A61K 39/0007 Nervous system antigens; Prions
• CPC Class Codes: A61K 39/39 characterised by the immunostimulating additives, e.g. chemical adjuvants
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• 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 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07K 14/4711 : Alzheimer's disease; Amyloid plaque core protein

Abstract

The invention relates to methods for treating human amyloid disease by administration of modified Aβ peptide immunogens.

Claims

1. A polymerized form of an immunogenic modified Aβ

peptide, which peptide contains Lysine substitutions in amino acid positions corresponding to amino acids 18 and 19 of Aβ

1-42, which polymerized form is soluble, non-fibrillogenic, has molecular weight less than 100 kDa, has the property of eliciting antibodies directed against the abnormal conformation of Aβ

in amyloid plaques and/or in soluble and semi-soluble Aβ

oligomers, and is produced using controlled polymerization of peptide monomers with glutaraldehyde.

2. The polymerized form of claim 1, wherein said modified Aβ

peptide is selected from the group consisting of Aβ

1-30 K₁₈K₁₉ (DAEFRHDSGYEVHHQKLKKFAEDVGSNKGA;

SEQ ID NO;

     1), Aβ

1-40 K₁₈K₁₉ (DAEFRHDSGYEVHHQKLKKFAEDVGSNKGAIIGLMVGGVV;

SEQ ID NO;

     2), Aβ

1-42 K₁₈K₁₉ (DAEFRHDSGYEVHHQKLKKFAEDVGSNKGAIIGLMVGGVVIA;

SEQ ID NO;

     3), Aβ

1-20 K₁₈K₁₉ (DAEFRHDSGYEVHHQKLKKF;

SEQ ID NO;

     4), Aβ

10-30 K₁₈K₁₉ (YEVHHQKLKKFAEDVGSNKGA;

SEQ ID NO;

     5), Aβ

10-40 K₁₈K₁₉ (YEVHHQKLKKFAEDVGSNKGAIIGLMVGGVV;

SEQ ID NO;

     6), and Aβ

10-42 K₁₈K₁₉ (YEVHHQKLKKFAEDVGSNKGAIIGLMVGGVVIA;

SEQ ID NO;

     7).

3. A pharmaceutical composition comprising one or more of the polymerized forms of claim 1 and a pharmaceutically acceptable carrier or diluent.

4. The pharmaceutical composition of claim 3, further comprising an adjuvant.