# US 6,875,434 B1 · Methods of treatment of Alzheimer's disease

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 6,875,434 B1
- Document ID: US6875434B1
- Status: Granted
- Kind: B1
- Application number: 09/724,953
- Filed: 2000-11-28
- Granted: 2005-04-05
- Earliest claimed: 1997-12-02
- Assignees: Neuralab Limited
- Inventors: Dale B. Schenk
- Web page: https://patentgrep.com/patent/US6875434B1

## CPC

- G01N 33/6896: {Neurological disorders, e.g. Alzheimer's disease}
- A61K 38/1709: {from mammals}
- A61K 38/193: {Colony stimulating factors [CSF]}
- A61K 39/0007: {Nervous system antigens; Prions}
- C07K 14/4711: {Alzheimer's disease; Amyloid plaque core protein}
- C07K 16/18: against material from animals or humans
- A61K 39/00: Medicinal preparations containing antigens or antibodies (materials for immunoassay G01N33/53)
- A61K 2039/505: {comprising antibodies}
- A61K 2039/53: {DNA (RNA) vaccination}
- A61K 2039/55505: {Inorganic adjuvants}
- A61K 2039/55555: {Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers}
- A61K 2039/55566: {Emulsions, e.g. Freund's adjuvant, MF59}
- A61K 2039/55572: {Lipopolysaccharides; Lipid A; Monophosphoryl lipid A}
- A61K 2039/55577: {Saponins; Quil A; QS21; ISCOMS}
- A61K 2039/6037: {Bacterial toxins, e.g. diphteria toxoid [DT], tetanus toxoid [TT]}
- A61K 2039/605: {MHC molecules or ligands thereof}
- C07K 2317/34: Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
- C07K 2319/00: Fusion polypeptide
- G01N 2800/2821: Alzheimer
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)

## Abstract

Disclosed are pharmaceutical compositions and methods for preventing or treating a number of amyloid diseases, including Alzheimer's disesase, 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

### Claim 1

A method of treating Alzheimer's disease in a mammalian subject, comprising administering to the subject a dosage of; (a) an immunogenic Aβ fragment effective to produce an immune response comprising antibodies against Aβ; and, (b) an adjuvant that augments the immune response to Aβ, thereby treating Alzheimer's disease.

### Claim 2 (depends on 1)

The method of claim 1 wherein said Aβ fragment induces an immune response directed against a neoepitope formed by amyloid deposits with respect to amyloid precursor protein (APP).

### Claim 3 (depends on 1)

The method of claim 1, wherein said adjuvant is selected from the group consisting of STIMULON QS-21, 3-De-O-acylated-monophosphoryl lipid A, and alum.

### Claim 4 (depends on 1)

The method of claim 1, wherein said immune response is characterized by a serum titer of the antibodies of a least 1:1000 with respect to Aβ.

### Claim 5 (depends on 4)

The method of claim 4, wherein said serum titer of the antibodies is at least 1:5000 with respect to Aβ.

### Claim 6 (depends on 1)

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

### Claim 7 (depends on 6)

The method of claim 6, wherein said serum titer of the antibodies is measured at a serum dilution of about 1:100.

### Claim 8 (depends on 1)

The method of claim 1, wherein the subject has a known risk of Alzheimer's disease.

### Claim 9 (depends on 1)

The method of claim 1, wherein said Aβ fragment is linked to a carrier molecule to form a conjugate.

### Claim 10 (depends on 1)

The method of claim 1, wherein said Aβ fragment is Aβ1-3.

### Claim 11 (depends on 10)

The method of claim 10, wherein said Aβ fragment is linked to a carrier molecule to form a conjugate.

### Claim 12 (depends on 1)

The method of claim 1, wherein said Aβ fragment is Aβ1-4.

### Claim 13 (depends on 12)

The method of claim 12, wherein said Aβ fragment is linked to a carrier molecule to form a conjugate.

### Claim 14 (depends on 1)

The method of claim 1, wherein said Aβ fragment is Aβ1-5.

### Claim 15 (depends on 14)

The method of claim 14, wherein said Aβ fragment is linked to a carrier molecule to form a conjugate.

### Claim 16 (depends on 1)

The method of claim 1, wherein said Aβ fragment is Aβ1-6.

### Claim 17 (depends on 16)

The method of claim 16, wherein said Aβ fragment is linked to a carrier molecule to form a conjugate.

### Claim 18 (depends on 1)

The method of claim 1, wherein said Aβ fragment is Aβ1-7.

### Claim 19 (depends on 18)

The method of claim 18, wherein said Aβ fragment is linked to a carrier molecule to form a conjugate.

### Claim 20 (depends on 1)

The method of claim 1, wherein said Aβ fragment is Aβ1-10.

### Claim 21 (depends on 20)

The method of claim 20, wherein said Aβ fragment is linked to a carrier molecule to form a conjugate.

### Claim 22 (depends on 1)

The method of claim 1, wherein said Aβ fragment is Aβ1-12.

### Claim 23 (depends on 22)

The method of claim 22, wherein said Aβ fragment is linked to a carrier molecule to form a conjugate.

### Claim 24 (depends on 1)

The method of claim 1, wherein said Aβ fragment is Aβ13-28.

### Claim 25 (depends on 24)

The method of claim 24, wherein said Aβ fragment is linked to a carrier molecule to form a conjugate.

### Claim 26 (depends on 1)

The method of claim 1, wherein said Aβ fragment is Aβ25-35.

### Claim 27 (depends on 26)

The method of claim 26, wherein said Aβ fragment is linked to a carrier molecule to form a conjugate.

### Claim 28 (depends on 1)

The method of claim 1, wherein said Aβ fragment is Aβ33-42.

### Claim 29 (depends on 28)

The method of claim 28, wherein said Aβ fragment is linked to a carrier molecule to form a conjugate.

### Claim 30

A method of prophylaxis of Alzheimer's disease in a mammalian subject, comprising administering to the subject a dosage of: (a) an immunogenic Aβ fragment effective to produce an immune response comprising antibodies against Aβ and, (b) an adjuvant that augments the immune response to the Aβ, thereby effecting prophylaxis of Alzheimer's disease.

### Claim 31 (depends on 30)

The method of claim 30, wherein said Aβ fragment induces an immune response directed against a neoepitope formed by amyloid deposits with respect to amyloid precursor protein (APP).

### Claim 32 (depends on 30)

The method of claim 30, wherein said adjuvant is selected from the group consisting of STIMULON QS-21, 3 De-O-acylated-monophosphoryl lipid A, and alum.

### Claim 33 (depends on 30)

The method of claim 30, wherein said immune response is characterized by a serum titer of the anti-Aβ antibodies of at least 1:1000 with respect to Aβ.

### Claim 34 (depends on 33)

The method of claim 33, wherein said serum titer of the antibodies is at least 1:5000 with respect to Aβ.

### Claim 35 (depends on 30)

The method of claim 30, wherein said immune response is characterized by a serum titer of the anti-Aβ antibodies corresponding to greater than about four times higher than a serum titer of anti-Aβ antibodies measured in a pre-treatment control serum sample.

### Claim 36 (depends on 30)

The method of claim 30, wherein said serum titer of the antibodies is measured at a serum dilution of about 1:100.

### Claim 37 (depends on 30)

The method of claim 30, wherein the subject has a known genetic risk of Alzheimer's disease.

### Claim 38 (depends on 30)

The method of claim 30, wherein said Aβ fragment is linked to a carrier molecule to form a conjugate.

### Claim 39 (depends on 30)

The method of claim 30, wherein said Aβ fragment is Aβ1-3.

### Claim 40 (depends on 39)

The method of claim 39, wherein said Aβ fragment is linked to a carrier molecule to form a conjugate.

### Claim 41 (depends on 30)

The method of claim 30, wherein said Aβ fragment is Aβ1-4.

### Claim 42 (depends on 41)

The method of claim 41, wherein said Aβ fragment is linked to a carrier molecule to form a conjugate.

### Claim 43 (depends on 30)

The method of claim 30, wherein said Aβ fragment is Aβ1-5.

### Claim 44 (depends on 43)

The method of claim 43, wherein said Aβ fragment is linked to a carrier molecule to form a conjugate.

### Claim 45 (depends on 30)

The method of claim 30, wherein said Aβ fragment is Aβ1-6.

### Claim 46 (depends on 45)

The method of claim 45, wherein said Aβ fragment is linked to a carrier molecule to form a conjugate.

### Claim 47 (depends on 30)

The method of claim 30, wherein said Aβ fragment is Aβ1-7.

### Claim 48 (depends on 47)

The method of claim 47, wherein said Aβ fragment is linked to a carrier molecule to form a conjugate.

### Claim 49 (depends on 30)

The method of claim 30, wherein said Aβ fragment is Aβ1-10.

### Claim 50 (depends on 41)

The method of claim 41, wherein said Aβ fragment is linked to a carrier molecule to form a conjugate.

### Claim 51 (depends on 30)

The method of claim 30, wherein said Aβ fragment is Aβ1-12.

### Claim 52 (depends on 51)

The method of claim 51, wherein said Aβ fragment is linked to a carrier molecule to form a conjugate.

### Claim 53 (depends on 30)

The method of claim 30, wherein said Aβ fragment is Aβ13-28.

### Claim 54 (depends on 53)

The method of claim 53, wherein said Aβ fragment is linked to a carrier molecule to form a conjugate.

### Claim 55 (depends on 30)

The method of claim 30, wherein said Aβ fragment is Aβ25-35.

### Claim 56 (depends on 55)

The method of claim 55, wherein said Aβ fragment is linked to a carrier molecule to form a conjugate.

### Claim 57 (depends on 30)

The method of claim 30, wherein said Aβ fragment is Aβ33-42.

### Claim 58 (depends on 57)

The method of claim 57, wherein said Aβ fragment is linked to a carrier molecule to form a conjugate.