# US 9,040,045 B2 · Methods and device to neutralize soluble toxic agents in the brain

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- Number: US 9,040,045 B2
- Document ID: US9040045B2
- Status: Granted
- Kind: B2
- Application number: 12/120,269
- Filed: 2008-05-14
- Published: 2008-11-20
- Granted: 2015-05-26
- Earliest claimed: 2007-05-14
- Assignees: Medtronic, Inc.
- Applicants: Lisa Lynn Shafer; Deepak Ramesh Thakker
- Inventors: Lisa Lynn Shafer; Deepak Ramesh Thakker
- Web page: https://patentgrep.com/patent/US9040045B2

## CPC

- C07K 16/18: against material from animals or humans
- 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
- A61K 2039/505: {comprising antibodies}
- A61K 2039/54: {characterised by the route of administration}
- A61K 2039/545: {characterised by the dose, timing or administration schedule}
- C07K 2317/54: F(ab')2
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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

Methods, agents and devices for treating a patient to reduce accumulation of certain proteins in the brain are described. Such proteins include Aβ, and the methods, agents and devices are useful for reducing the accumulation of Aβ, which is a principal constituent of the plaques associated with such diseases as Alzheimer's disease (AD). Antibodies to Aβ, when delivered systemically or directly into the central nervous system, improve cognitive deficits in a transgenic mouse model of AD. However, unlike peripheral of antibodies to Aβ, which increased cerebral vascular plaques and hemorrhages, direct central administration did not result in such an increase cerebral vascular plaques and hemorrhages.

## Claims

### Claim 1

A method for treating a subject having cerebral amyloid angiopathy, comprising:
chronically delivering to a cerebral ventricle of the subject an anti-Aβ antibody in an amount effective to treat the cerebral amyloid angiopathy,
wherein the anti-Aβ antibody is chronically delivered to the subject's cerebral ventricle from a reservoir of an implantable infusion device.

### Claim 2 (depends on 1)

The method of claim 1, further comprising introducing a composition comprising the antibody to the reservoir.

### Claim 3 (depends on 1)

The method of claim 1, wherein chronically delivering the antibody comprises delivering the antibody for a month or longer.

### Claim 4

The method of clam 3, wherein the antibody is continuously delivered for a month or longer.

### Claim 5 (depends on 4)

The method of claim 4, wherein the continuous delivery includes pulsed boluses of increased delivery rate.