Method of treating or ameliorating an immune cell associated pathology using GITR ligand antibodies

• US 7,618,632 B2
• Filed: 05/24/2004
• Issued: 11/17/2009
• Est. Priority Date: 05/23/2003
• Status: Active Grant

• Current Assignee: United States Department Of Health And Human Services
• Original Assignee: Wyeth (Pfizer Inc.), United States Department Of Health And Human Services
• Inventors: Collins, Mary, Carreno, Beatriz M., McHugh, Rebecca Suzanne, Shevach, Ethan Menahem, Whitters, Matthew James, Stephens, Geoffrey Laurence, Young, Deborah Ann, Byrne, Michael Chapman, Reddy, Padmalatha S.
• Primary Examiner(s): Landsman; Robert
• Assistant Examiner(s): Hissong; Bruce D
• Application Number:
  US10/853,032
• Publication Number:
  US 20050014224A1
• Time in Patent Office: 2,003 Days
• Field of Search: None
• US Class Current: 424/144.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• 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: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: C07K 14/47 from mammals
• CPC Class Codes: C07K 14/525 Tumour necrosis factor [TNF]
• CPC Class Codes: C07K 16/241 Tumor Necrosis Factors
• CPC Class Codes: C07K 16/2866 against receptors for cytokines, lymphokines, interferons
• CPC Class Codes: C07K 2317/73 Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
• CPC Class Codes: G01N 33/566 : using specific carrier or receptor proteins as ligand binding reagents where possible specific carrier or receptor proteins are classified with their target compounds

Abstract

The present invention provides novel isolated and purified polynucleotides and polypeptides related to a novel ligand for glucocorticoid-induced TNF receptor (GITR). The invention also provides antibodies to the GITR ligand (GITRL). The present invention also is directed to novel methods for diagnosing, prognosing, monitoring the progress of, and treating disorders arising from disregulation of the immune system (e.g., autoimmune disorders, inflammatory diseases, and transplant rejection, and cancers and infectious diseases) using GITRL and/or modulators of GITRL. The present invention is further directed to novel therapeutics and therapeutic targets and to methods of screening and assessing test compounds for the intervention (treatment) and prevention of said disorders arising from disregulation of the immune system, as related to GITRL and GITR.

Claims

1. A method of treating or ameliorating an immune cell-associated pathology in a subject for whom suppression of immune response is desired, wherein the immune cell is a T cell, comprising administering to the subject a therapeutically effective amount of a neutralizing anti-Glucocorticoid-Induced TNF Receptor Ligand antibody (anti-GITRL antibody), wherein the anti-GITRL antibody is a 5F1 antibody, a 10F12 antibody, or an antigen-binding fragment thereof, and wherein the anti-GITRL antibody treats or ameliorates the immune cell-associated pathology by blocking GITRL binding to the Glucocorticoid-Induced TNF Receptor (GITR) on effector T cells, and wherein the immune cell-associated pathology is selected from the group consisting of rheumatoid arthritis, encephalomyelitis, multiple sclerosis, osteoarthritis, autoimmune gastritis, psoriasis and other inflammatory dermatoses, asthma, allergy, organ transplant rejection, graft-versus-host disease, and inflammatory bowel diseases, including Crohn'"'"'s disease and ulcerative colitis.

2. The method of claim 1, wherein the method comprises administering the anti-GITRL antibody such that the susceptibility of effector T cells in the subject to suppression by CD4⁺CD25⁺ regulatory T cells is maintained.

3. The method of claim 1, wherein the immune cell-associated pathology is multiple sclerosis.

4. The method of claim 1, where in the effector T cells are CD4⁺CD25⁻

T cells.