# US 7,744,885 B2 · Methods of treating vascular inflammatory pathology using anti-TNF antibodies and fragments thereof

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

- Number: US 7,744,885 B2
- Document ID: US7744885B2
- Status: Granted
- Kind: B2
- Application number: 12/001,071
- Filed: 2007-12-07
- Published: 2009-01-22
- Granted: 2010-06-29
- Earliest claimed: 1991-03-18
- Assignees: Centocor, Inc.; New York University
- Inventors: Junming Le; Jan Vilcek; Peter Daddona; John Ghrayeb; David Knight; Scott Siegel
- Web page: https://patentgrep.com/patent/US7744885B2

## CPC

- C07K 16/241: {Tumor Necrosis Factors}
- A61K 31/167: having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
- A61K 31/192: having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid {(cannabinoids A61K31/658)}
- A61K 31/196: the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
- A61K 31/405: Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
- A61K 31/485: Morphinan derivatives, e.g. morphine, codeine
- A61K 31/573: substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61P 9/00: Drugs for disorders of the cardiovascular system
- C07K 14/525: Tumour necrosis factor [TNF]
- C07K 16/30: from tumour cells
- 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 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 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2319/00: Fusion polypeptide
- 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)
- 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

## Abstract

Anti-TNF antibodies, fragments and regions thereof which are specific for human tumor necrosis factor-α (TNFα) and are useful in vivo diagnosis and therapy of a number of TNFα-mediated pathologies and conditions, as well as polynucleotides coding for murine and chimeric antibodies, methods of producing the antibody, methods of use of the anti-TNF antibody, or fragment, region or derivative thereof, in immunoassays and immunotherapeutic approaches are provided.

## Claims

### Claim 1

A method of inhibiting or neutralizing TNFα in a human patient, wherein said human patient has a vascular inflammatory pathology, comprising administering to said human patient a TNFα-inhibiting effective amount of an anti-TNFα antibody or antigen-binding fragment thereof, said antibody comprising a human constant region, wherein said anti-TNFα antibody or antigen-binding fragment (i) competitively inhibits binding of A2 (ATCC Accession No. PTA-7045) to human TNFα, and (ii) binds to human TNFα with an affinity of at least 1×108 liter/mole, measured as an association constant (Ka).

### Claim 2 (depends on 1)

The method of claim 1, wherein said vascular inflammatory pathology is Kawasaki's pathology.

### Claim 3 (depends on 1)

The method of claim 1, wherein said vascular inflammatory pathology is disseminated intravascular coagulation.

### Claim 4 (depends on 1)

The method of claim 1, wherein said vascular inflammatory pathology is atherosclerosis.

### Claim 5 (depends on 1)

The method of claim 1, wherein said anti-TNFα antibody or antigen-binding fragment is administered to the human patient by means of parenteral administration.

### Claim 6 (depends on 1)

The method of claim 1, wherein said anti-TNFα antibody or antigen-binding fragment is administered to the human by means of intravenous administration, subcutaneous administration or intramuscular administration.

### Claim 7 (depends on 1)

The method of claim 1, wherein said anti-TNF antibody is of immunoglobulin class IgG1, IgG2, IgG3, IgG4 or IgGA.

### Claim 8 (depends on 1)

The method of claim 1, wherein said anti-TNF antibody is a fragment selected from the group consisting of Fab, Fab′, F(ab′)2 and Fv.

### Claim 9 (depends on 1)

The method of claim 1, wherein said anti-TNFα antibody or antigen-binding fragment comprises an IgG1 constant region.

### Claim 10

A method of inhibiting or neutralizing TNFα in a human patient, wherein said human patient has a vascular inflammatory pathology, comprising administering to said human patient a TNFα-inhibiting effective amount of an anti-TNFα antibody or antigen-binding fragment thereof, said antibody comprising a human constant region, wherein said anti-TNFα antibody or antigen-binding fragment (i) comprises the antigen-binding regions of A2 (ATCC Accession No. PTA-7045), and (ii) binds to human TNF-α with an affinity of at least 1×108 liter/mole, measured as an association constant (Ka).

### Claim 11

A method of inhibiting or neutralizing TNFα in a human patient, wherein said human patient has a vascular inflammatory pathology, comprising administering to said human patient a TNFα-inhibiting effective amount of an anti-TNFα antibody or antigen-binding fragment thereof, said antibody comprising a human constant region, wherein said anti-TNFα antibody or antigen-binding fragment (i) has epitopic specificity identical to A2 (ATCC Accession No. PTA-7045), and (ii) binds to human TNF-α with an affinity of at least 1×108 liter/mole, measured as an association constant (Ka).

### Claim 12 (depends on 1)

The method of claim 1, wherein the antibody or antigen-binding fragment comprises a human constant region and a human variable region.

### Claim 13 (depends on 1)

The method of claim 1, wherein said antibody or antigen-binding fragment comprises at least one human light chain and at least one human heavy chain.

### Claim 14 (depends on 1)

The method of claim 1, wherein said anti-TNFα antibody or antigen-binding fragment is a chimeric antibody.

### Claim 15 (depends on 1)

The method of claim 1, wherein said anti-TNFα antibody or antigen-binding fragment is a human antibody.

### Claim 16 (depends on 1)

The method of claim 1, wherein said anti-TNFα antibody or antigen-binding fragment is a humanized antibody.

### Claim 17 (depends on 1)

The method of claim 1, comprising administering a composition comprising said anti-TNFα antibody or antigen-binding fragment and a pharmaceutically acceptable carrier.

### Claim 18 (depends on 1)

The method of claim 1, wherein said TNFα-inhibiting effective amount of said anti-TNFα antibody or antigen-binding fragment comprises a single or divided dose of about 0.5-50 mg/kg.

### Claim 19 (depends on 18)

The method of claim 18, wherein the single or divided dose is 1-10 mg/kg.

### Claim 20 (depends on 13)

The method of claim 13, wherein the light chain comprises all antigen-binding regions of the light chain of A2 (ATCC Accession No. PTA-7045).

### Claim 21 (depends on 13)

The method of claim 13, wherein the heavy chain comprises all antigen-binding regions of the heavy chain of A2 (ATCC Accession No. PTA-7045).

### Claim 22 (depends on 13)

The method of claim 13, wherein the light chain comprises all antigen-binding regions of the light chain of A2 (ATCC Accession No. PTA-7045) and the heavy chain comprises all antigen-binding regions of the heavy chain of A2 (ATCC Accession No. PTA-7045).