# US 10,119,979 B2 · Methods of treating stroke and traumatic brain injury using humanized AQC2 anti-VLA-1 antibodies

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- Number: US 10,119,979 B2
- Document ID: US10119979B2
- Status: Granted
- Kind: B2
- Application number: 12/301,988
- Filed: 2007-05-24
- Published: 2010-09-16
- Granted: 2018-11-06
- Earliest claimed: 2006-05-25
- Assignees: Biogen MA Inc.
- Applicants: Jane K. Relton; Humphrey Gardner
- Inventors: Jane K. Relton; Humphrey Gardner
- Web page: https://patentgrep.com/patent/US10119979B2

## CPC

- G01N 33/6896: {Neurological disorders, e.g. Alzheimer's disease}
- A61K 31/00: Medicinal preparations containing organic active ingredients
- A61K 38/193: {Colony stimulating factors [CSF]}
- A61K 38/49: Urokinase; Tissue plasminogen activator
- A61P 7/04: Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 25/00: Drugs for disorders of the nervous system
- 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
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 16/2842: {against integrin beta1-subunit-containing molecules, e.g. CD29, CD49}
- A61K 2039/505: {comprising antibodies}
- G01N 2800/2871: Cerebrovascular disorders, e.g. stroke, cerebral infarct, cerebral haemorrhage, transient ischemic event
- 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)
- 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

Methods and compositions for treating stroke are disclosed.

## Claims

### Claim 1

A method of treating a traumatic brain injury (TBI) in a subject, the method comprising administering to the subject a humanized AQC2 anti-VLA-1 (Very Late Activation Antigen-I) antibody, or an antigen-binding fragment thereof, wherein the anti-VLA-1 antibody, or antigen-binding fragment thereof, is first administered within 48 hours of the TBI, and wherein the anti-VLA-1 antibody, or antigen-binding fragment thereof, reduces infarct size in a hemisphere affected by the TBI, such that the percentage of the hemisphere infarcted is 40% or less, and wherein the anti-VLA-1 antibody or antigen-binding fragment thereof is administered at a dosage from 0.1 mg/kg per day to 5 mg/kg per day.

### Claim 2 (depends on 1)

The method of claim 1, wherein the TBI is a contusion, bruise, laceration or hematoma.

### Claim 3 (depends on 1)

The method of claim 1, wherein the administering step reduces the infarct size by at least 10% in the hemisphere affected by the TBI, as compared to an infarct size in an untreated subject.

### Claim 4 (depends on 1)

The method of claim 1, wherein the administering step reduces the infarct size by at least 20% in the hemisphere affected by the TBI, as compared to an infarct size in an untreated subject.

### Claim 5 (depends on 1)

The method of claim 1, wherein the administering step reduces edema, such that the size of the hemisphere affected by the TBI is increased by no more than 10% following the TBI.

### Claim 6

A method of treating a stroke in a subject, the method comprising administering to the subject a humanized AQC2 anti-VLA-1 (Very Late Activation Antigen-1) antibody, or an antigen-binding fragment thereof, wherein the anti-VLA-1 antibody, or antigen-binding fragment thereof, is first administered within 48 hours of the stroke, and wherein the anti-VLA-1 antibody, or antigen-binding fragment thereof, reduces infarct size in a hemisphere affected by the stroke, such that the percentage of the hemisphere infarcted is 40% or less, and wherein the anti-VLA-1 antibody or antigen-binding fragment thereof is administered at a dosage from 0.1 mg/kg per day to 5 mg/kg per day.

### Claim 7 (depends on 6)

The method of claim 6, wherein the humanized AQC2 anti-VLA-1 antibody, or antigen-binding fragment thereof, is produced by a hybridoma having ATCC Deposit No. PTA3275.

### Claim 8 (depends on 6)

The method of claim 6, wherein the anti-VLA-1 antibody or antigen-binding fragment thereof is effective to improve neurologic function.

### Claim 9 (depends on 6)

The method of claim 6, wherein the stroke is an ischemic stroke.

### Claim 10 (depends on 6)

The method of claim 6, wherein the stroke is an hemorrhagic stroke.

### Claim 11 (depends on 6)

The method of claim 6, wherein the subject is a mammal.

### Claim 12 (depends on 11)

The method of claim 11, wherein the subject is a human.

### Claim 13 (depends on 6)

The method of claim 6, wherein the anti-VLA-1 antibody or antigen-binding fragment thereof is administered intravenously or parenterally.

### Claim 14 (depends on 6)

The method of claim 6, wherein the anti-VLA-1 antibody or antigen-binding fragment thereof is administered at least twice within 7 days after the stroke.

### Claim 15 (depends on 6)

The method of claim 6, wherein the administering step reduces the infarct size by at least 10% in the hemisphere affected by the stroke, as compared to an infarct size in an untreated subject.

### Claim 16 (depends on 6)

The method of claim 6, wherein the administering step reduces the infarct size by at least 20% in the hemisphere affected by the stroke, as compared to an infarct size in an untreated subject.

### Claim 17 (depends on 6)

The method of claim 6, wherein the administering step reduces edema, such that the size of the hemisphere affected by the stroke is increased by no more than 10% following the stroke.

### Claim 18 (depends on 6)

The method of claim 6, wherein the anti-VLA-1 antibody or antigen-binding fragment thereof is administered in combination with another therapeutic agent.

### Claim 19 (depends on 18)

The method of claim 18, wherein the other therapeutic agent is selected from the group consisting of an antiplatelet agent, a thrombolytic enzyme, an aggregation inhibitor, a glycoprotein IIb/IIIa inhibitor, a glycosaminoglycan, a thrombin inhibitor, an anticoagulant, heparin, coumarin, tPA, GCSF, streptokinase, urokinase, Ancrod, acetylsalicyclic acid, melatonin, and a caspase inhibitor.