Methods of Treating Hepatitis With Anti-TNF alpha Antibodies

• US 20130183298A1
• Filed: 03/05/2013
• Published: 07/18/2013
• Est. Priority Date: 03/18/1991
• Status: Abandoned Application

• Current Assignee: Janssen Biotech, Inc. (Johnson & Johnson), New York University
• Original Assignee: Janssen Biotech, Inc. (Johnson & Johnson), New York University
• Inventors: Le, Junming, Vilcek, Jan T., Daddona, Peter E., Ghrayeb, John, Knight, David M., Siegel, Scott A.
• Application Number:
  US13/786,445
• Publication Number:
  US 20130183298A1
• Time in Patent Office: Days
• US Class Current: 424/133.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/167 having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• CPC Class Codes: A61K 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• CPC Class Codes: A61K 31/196 the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
• CPC Class Codes: A61K 31/405 Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: 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
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61K 45/00 Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: C07K 14/525 Tumour necrosis factor [TNF]
• CPC Class Codes: C07K 16/241 Tumor Necrosis Factors
• CPC Class Codes: C07K 16/30 from tumour cells
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/34 Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/92 : Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
• CPC Class Codes: C07K 2319/00 : Fusion polypeptide

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

1. A method of treating hepatitis in a human in need thereof, comprising administering to the human an effective TNFα

-inhibiting amount of an anti-TNFα

chimeric antibody or antigen-binding fragment thereof for a sufficient period of time to treat the hepatitis, wherein said anti-TNFα

chimeric antibody or antigen-binding fragment (i) competitively inhibits binding of A2 (ATCC Accession No. PTA-7045) to human TNFα and

(ii) binds to a neutralizing epitope of human TNFα

with an affinity of at least 1×

10⁸ liter/mole, measured as an association constant (Ka), as determined by Scatchard analysis, wherein the hepatitis is alcohol-induced hepatitis.

2. The method of claim 1, wherein said anti-TNFα

chimeric antibody or antigen-binding fragment comprises an IgG1 constant region.

3. The method of claim 1, further comprising administering to the human an effective amount of a therapeutic agent selected from the group consisting of:

an antirheumatic, a muscle relaxant, a narcotic, a non-steroid anti-inflammatory drug (NSAID), an analgesic, an anesthetic, a sedative, a local anethetic, a neuromuscular blocker, an antimicrobial, an antipsoriatic, a corticosteriod, an anabolic steroid, a diabetes related agent, a mineral, a nutritional, a thyroid agent, a vitamin, a calcium related hormone, an antidiarrheal, an antitussive, an antiemetic, an antiulcer, a laxative, an anticoagulant, an erythropoietin, a filgrastim, a sargramostim, an immunization, an immunoglobulin, an immunosuppressive, a growth hormone, a hormone replacement drug, an estrogen receptor modulator, a mydriatic, a cycloplegic, an alkylating agent, an antimetabolite, a mitotic inhibitor, a radiopharmaceutical, an antidepressant, an antimanic agent, an antipsychotic, an anxiolytic, a hypnotic, a sympathomimetic, a stimulant, donepezil, tacrine, an asthma medication, a beta agonist, an inhaled steroid, a leukotriene inhibitor, a methylxanthine, a cromolyn, an epinephrine, an epinephrine analog, dornase alpha, a cytokine and a cytokine antagonist.

4. The method of claim 1, further comprising administering to the human an effective amount of a disease modifying anti-rheumatic drug.

5. The method of claim 1, further comprising administering to the human an effective amount of an anti-inflammatory agent.

6. The method of claim 1, further comprising administering to the human an effective amount of methotrexate.

7. The method of claim 1, further comprising administering to the human an effective amount of a pain control agent.

8. The method of claim 1, further comprising administering to the human an effective amount of at least one therapeutic agent selected from the group consisting of:

at least one antibiotic and at least one steroid.

9. The method of claim 1, wherein the anti-TNFα

chimeric antibody or antigen-binding fragment is administered at a dose of 1.0-5 mg/kg or 5-10 mg/kg.

10. The method of claim 1, wherein the anti-TNFα

chimeric antibody or antigen-binding fragment is administered to the human by means of parenteral administration.

11. The method of claim 1, wherein the anti-TNFα

chimeric antibody is of immunoglobulin class IgG1, IgG2, IgG3, IgG4 or IgM.

12. The method of claim 1, wherein the antigen-binding fragment is a fragment selected from the group consisting of Fab, Fab′

, F(ab′

)₂ and Fv.

13. The method of claim 1 comprising administering to the human an initial 5 mg/kg dose of the anti-TNFα

chimeric antibody or antigen-binding fragment, followed by another 5 mg/kg dose of said anti-TNFα

chimeric antibody or antigen-binding fragment at two weeks, six weeks and every six weeks thereafter for a sufficient period of time to treat the alcohol-induced hepatitis, wherein said anti-TNFα

chimeric antibody or antigen-binding fragment competitively inhibits binding of TNFα

to monoclonal antibody cA2.

14. The method of claim 1, wherein the light chain of the antibody comprises all antigen-binding regions of the light chain of A2 (ATCC Accession No. PTA-7045).

15. The method of claim 1, wherein the heavy chain of the antibody comprises all antigen-binding regions of the heavy chain of A2 (ATCC Accession No. PTA-7045).

16. The method of claim 1, wherein the light chain of the antibody comprises all antigen-binding regions of the light chain of A2 (ATCC Accession No. PTA-7045) and the heavy chain of the antibody comprises all antigen-binding regions of the heavy chain of A2 (ATCC Accession No. PTA-7045).

17. A method of treating hepatitis in a human in need thereof, comprising administering to the human an effective TNFα

-inhibiting amount of an anti-TNFα

chimeric antibody or antigen-binding fragment thereof for a sufficient period of time to treat the hepatitis, wherein said anti-TNFα

chimeric antibody or antigen-binding fragment (i) competitively inhibits binding of A2 (ATCC Accession No. PTA-7045) to human TNFα and

(ii) binds to a neutralizing epitope of human TNFα

with an affinity of at least 1×

10⁸ liter/mole, measured as an association constant (Ka), as determined by Scatchard analysis, wherein the hepatitis is hepatitis C.