# US 7,408,027 B1 · Tools for the diagnosis and treatment of Alzheimer's disease

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- Number: US 7,408,027 B1
- Document ID: US7408027B1
- Status: Granted
- Kind: B1
- Application number: 09/640,737
- Filed: 2000-08-17
- Granted: 2008-08-05
- Earliest claimed: 1994-11-28
- Assignees: Max-Planck Gesellschaft Zur Forderung der Wissenchaften
- Inventors: Eva-Maria Mandelkow; Eckhard Mandelkow; Birgit Lichtenberg-Kraag; Jacek Biernat; Gerard Drewes; Barbara Steiner
- Web page: https://patentgrep.com/patent/US7408027B1

## CPC

- C07K 14/4711: {Alzheimer's disease; Amyloid plaque core protein}
- C07K 16/18: against material from animals or humans
- C07K 16/40: against enzymes
- C12N 9/12: transferring phosphorus containing groups, e.g. kinases (2.7)
- C12N 9/1205: {Phosphotransferases with an alcohol group as acceptor (2.7.1), e.g. protein kinases}
- C12N 9/16: acting on ester bonds (3.1)
- G01N 33/6896: {Neurological disorders, e.g. Alzheimer's disease}
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- A61K 39/00: Medicinal preparations containing antigens or antibodies (materials for immunoassay G01N33/53)
- G01N 2333/4709: Amyloid plaque core protein
- G01N 2800/2821: Alzheimer
- 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)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- 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)

## Abstract

The invention relates to epitopes of the tau protein which are specifically occurring in a phosphorylated state in tau protein from Alzheimer paired helical filaments, to protein kinases which are responsible for the phosphorylation of the amino acids of the tau protein giving rise to said epitopes, and to antibodies specific for said epitopes. The invention further relates to pharmaceutical compositions for the treatment or prevention of Alzheimer's disease, to diagnostic compositions and methods for the detection of Alzheimer's disease and to the use of said epitopes for the generation of antibodies specifically detecting Alzheimer tau protein. Additionally, the invention relates to methods for testing drugs effective in dissolving Alzheimer paired helical filaments or preventing the formation thereof.

## Claims

### Claim 1

An immunogenic composition characterized by the ability to generate an antibody which distinguishes between phosphorylated and dephosphorylated tau comprising:
(a) a tau peptide consisting of the tau amino acid sequence Lys-Ile-Gly-Ser-Thr-Glu-Asn-Leu-Lys (residues 259-267 in SEQ ID NO: 1) conjugated to
(b) a carrier molecule, wherein the carrier molecule induces or enhances an immune response to the peptide of (a).

### Claim 2 (depends on 1)

The immunogenic composition of claim 1, wherein the Ser (residue 262 of SEQ ID NO:1) is phosphorylated.

### Claim 3

A method of producing an antibody which distinguishes between phosphorylated and dephosphorylated tau, the method comprising administering to an animal an antibody-producing amount of an immunogenic composition comprising:
(a) a peptide consisting of the tau amino acid sequence Lys-Ile-Gly-Ser-Thr-Glu-Asn-Leu-Lys (residues 259-267 in SEQ ID NO: I) conjugated to
(b) a carrier molecule, wherein the carrier molecule induces or enhances an immune response to the peptide of (a).

### Claim 4

A method of producing an antibody which distinguishes between phosphorylated and dephosphorylated tau, the method comprising administering to an animal an antibody-producing amount of an immunogenic composition comprising:
(a) a peptide consisting of the tau amino acid sequence Lys-Ile-Gly-Ser-Thr-Glu-Asn-Leu-Lys (residues 259-267 in SEQ ID NO: 1) conjugated to
(b) a carrier molecule, wherein the carrier molecule induces or enhances an immune response to the peptide of (a);
wherein the Ser (residue 262 of SEQ ID NO: 1) is phosphorylated.
