# US 2013/0156759 A1 · Methods of treating dementia using a gm-csf antagonist

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- Number: US 2013/0156759 A1
- Document ID: US20130156759A1
- Status: Published application
- Kind: A1
- Application number: 13/774,367
- Filed: 2013-02-22
- Published: 2013-06-20
- Earliest claimed: 2006-11-21
- Assignees: KaloBios Pharmaceuticals, Inc.
- Inventors: Christopher R. Bebbington; Geoffrey T. Yarranton; Varghese Palath
- Web page: https://patentgrep.com/patent/US20130156759A1

## CPC

- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61K 31/505: Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K 31/519: ortho- or peri-condensed with heterocyclic rings
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- 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
- C07K 16/243: {Colony Stimulating Factors}
- A61K 2039/505: {comprising antibodies}
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- 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 2317/55: Fab or Fab'
- C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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

The invention is based on the discovery that GM-CSF antagonists can be used for the treatment of a patient that has Alzheimer's disease or vascular dementia, or is at risk for developing Alzheimer's disease. Accordingly, the invention provides methods of administering a GM-CSF antagonist, e.g., a GM-CSF antibody and pharmaceutical compositions comprising such antagonists.

## Claims

### Claim 1

A method for treating a patient suffering from vascular dementia or cerebral amyloid angiopathy, the method comprising administering a recombinant GM-CSF antagonist to the patient, wherein the recombinant GM-CSF antagonist is provided in a therapeutically effective amount.

### Claim 2 (depends on 1)

The method of claim 1, wherein the recombinant GM-CSF antagonist is provided in an amount to prevent cognitive decline.

### Claim 3 (depends on 1)

The method of claim 1, wherein the patient has mild cognitive impairment.

### Claim 4 (depends on 1)

The method of claim 1, wherein the patient has cerebral amyloid angiopathy.

### Claim 5 (depends on 1)

The method of claim 1, wherein the patient has elevated levels of GM-CSF in the cerebrospinal fluid (CSF) or serum, or both CSF and serum.

### Claim 6 (depends on 1)

The method of claim 1, wherein the recombinant GM-CSF antagonist is administered using intrathecal or perispinal administration.

### Claim 7 (depends on 1)

The method of claim 1, wherein the recombinant GM-CSF antagonist is a neutralizing anti-GM-CSF antibody

### Claim 8 (depends on 7)

The method of claim 7, wherein the neutralizing anti-GM-CSF antibody is an antibody fragment that is a Fab, a Fab′, a F(ab′)2, a scFv, or a dAB.

### Claim 9 (depends on 8)

The method of claim 8, wherein the antibody fragment is conjugated to polyethylene glycol.

### Claim 10 (depends on 7)

The method of claim 7, wherein the neutralizing anti-GM-CSF antibody has a KD of less than 100 pM.

### Claim 11 (depends on 7)

The method of claim 7, wherein the neutralizing anti-GM-CSF antibody is a chimeric antibody.

### Claim 12 (depends on 7)

The method of claim 7, wherein the neutralizing anti-GM-CSF antibody is a human antibody.

### Claim 13 (depends on 7)

The method of claim 7, wherein the neutralizing anti-GM-CSF antibody comprises a human variable region.

### Claim 14 (depends on 7)

The method of claim 7, wherein the neutralizing anti-GM-CSF antibody comprises a human light chain constant region and/or a human heavy chain constant region.

### Claim 15 (depends on 14)

The method of claim 14, wherein the human heavy chain constant region is a gamma subclass.

### Claim 16 (depends on 7)

The method of claim 7, wherein the neutralizing anti-GM-CSF antibody binds to the same epitope as chimeric 19/2.

### Claim 17 (depends on 7)

The method of claim 7, wherein the neutralizing anti-GM-CSF antibody comprises a heavy chain variable (VH) region having the sequence of SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, or SEQ ID NO:13.

### Claim 18 (depends on 7)

The method of claim 7, wherein the neutralizing anti-GM-CSF antibody comprises a light chain variable (VL) region having the sequence of SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, or SEQ ID NO:18.

### Claim 19 (depends on 7)

The method of claim 7, wherein the neutralizing anti-GM-CSF antibody comprises a VH region having the sequence of SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, or SEQ ID NO:13; and a VL region having the sequence of SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, or SEQ ID NO:18.