Method for treating amyloid disease

• US 9,770,496 B2
• Filed: 03/21/2016
• Issued: 09/26/2017
• Est. Priority Date: 07/19/2011
• Status: Active Grant

• Current Assignee: New York University
• Original Assignee: New York University
• Inventors: Wisniewski, Thomas, Goni, Fernando
• Primary Examiner(s): BALLARD, KIMBERLY
• Application Number:
  US15/076,122
• Publication Number:
  US 20160303208A1
• Time in Patent Office: 554 Days
• 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 covalently bonded to an adjuvant polypeptide when produced using controlled polymerization with glutaraldehyde, and is soluble and non-fibrillogenic.

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. The polymerized form of claim 1, wherein the adjuvant polypeptide is an enterotoxin, tetanus toxoid, or flagellin.

4. The polymerized form of claim 3, wherein the enterotoxin is Cholera toxin B (CTB) subunit.

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

6. The pharmaceutical composition of claim 5 formulated for mucosal administration.

7. The pharmaceutical composition of claim 5 formulated for oral administration.

8. A method for treating a patient suffering from an amyloid disease or a tauopathy comprising administering to the patient a therapeutically effective amount of the polymerized form of claim 1.

9. The method of claim 8, wherein two or more different polymerized forms are administered.

10. The method of claim 8, further comprising administering a polymerized British amyloidosis related peptide (pBri).

11. The method of claim 10, wherein the monomer of the pBri peptide has the sequence CSRTVKKNIIEEN (SEQ ID NO:

8).

12. The method of claim 8, wherein the amyloid disease is selected from the group consisting of Alzheimer'"'"'s disease, Lewy Body Dementia, Frontotemporal dementia, Parkinson'"'"'s disease, Down syndrome, Creutzfeldt-Jakob disease, Gerstmann-Straussler-Scheinker disease, chronic traumatic encephalopathy, and progressive supranuclear palsy.

13. The method of claim 8, wherein the amyloid disease is associated with accumulation of Aβ

in one or more bodily fluids.

14. The method of claim 8, wherein the polymerized form is administered mucosally.

15. The method of claim 8, wherein the polymerized form is administered orally.

16. The method of claim 8, wherein the patient is human.