Methods and compositions for decreasing T-cell activity

• US 7,964,190 B2
• Filed: 02/28/2003
• Issued: 06/21/2011
• Est. Priority Date: 03/22/1996
• Status: Expired due to Fees

• Current Assignee: Human Genome Sciences Incorporated (GlaxoSmithKline PLC)
• Original Assignee: Human Genome Sciences Incorporated (GlaxoSmithKline PLC)
• Inventors: Ruben, Steven M, Ullrich, Stephen, Zhai, Yifan, Yu, Guo-Liang, Ebner, Reinhard
• Primary Examiner(s): Landsman; Robert
• Assistant Examiner(s): DANG, IAN D
• Application Number:
  US10/375,680
• Publication Number:
  US 20040009147A1
• Time in Patent Office: 3,035 Days
• Field of Search: None
• US Class Current: 424/130.1
• 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 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: C07K 14/4747 Apoptosis related proteins
• CPC Class Codes: C07K 14/70575 NGF/TNF-superfamily, e.g. CD70, CD95L, CD153, CD154 NGF C07K14/48, TNF C07K14/525
• CPC Class Codes: C07K 16/2866 against receptors for cytokines, lymphokines, interferons
• CPC Class Codes: C07K 16/2875 against the NGF/TNF superfamily, e.g. CD70, CD95L, CD153, CD154 against NGF C07K16/22, against TNF C07K16/241
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• 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 2317/622 Single chain antibody (scFv)
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: C07K 2319/30 Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
• CPC Class Codes: C12N 2799/026 where the vector is derived from a baculovirus
• CPC Class Codes: C12N 2799/027 where the vector is derived from a retrovirus

Abstract

The present invention relates to a novel member of the TNF-Ligand superfamily. More specifically, isolated nucleic acid molecules are provided encoding a human Apoptosis Inducing Molecule II (AIM II). AIM II polypeptides are also provided, as are vectors, host cells and recombinant methods for producing the same. The invention further relates to screening methods for identifying agonists and antagonists of AIM II activity. Also provided are therapeutic methods for treating lymphadenopathy, aberrant bone development, autoimmune and other immune system diseases, graft versus host disease, rheumatoid arthritis, osteoarthritis and to inhibit neoplasia, such as tumor cell growth.

Claims

1. A method for decreasing a T-cell activity in an individual suffering from acute graft-versus-host disease comprising administering to the individual therapeutically effective amounts of:

a) a first therapeutic agent comprising an antibody which specifically binds to the polypeptide consisting of SEQ ID NO;

2, wherein the antibody decreases a T-cell activity in vitro; and

b) a second therapeutic agent selected from the group consisting of;

(i) a tumor necrosis factor;

(ii) an immunosuppressive agent;

(iii) an antibiotic;

(iv) an anti-inflammatory agent;

(v) a chemotherapeutic agent;

(vi) a cytokine;

(vii) an angiogenic agent; and

(viii) a fibroblast growth factor;

wherein decreasing a T-cell activity comprises one or more of;

decreasing T-cell proliferation;

decreasing gamma-IFN secretion by T-cells; and

decreasing the activation of CD8+ T-cells.

2. The method of claim 1, wherein said first and second therapeutic agents are administered to the individual at the same time.

3. The method of claim 1, wherein said tumor necrosis factor is selected from the group consisting of:

a) TNF-α

;

b) TNF-β

; and

c) TNF-γ

.

4. The method of claim 1, wherein said immunosuppressive agent is selected from the group consisting of:

a) cyclosporine;

b) cyclophosphamide methylprednisone;

c) prednisone;

d) azathioprine;

e) FK-506; and

f) 15-deoxyspergualin.

5. The method of claim 1, wherein said cytokine is selected from the group consisting of:

a) IL-2;

b) IL-3;

c) IL-4;

d) IL-5;

e) IL-6;

f) IL-7;

g) IL-10;

h) IL-12;

i) IL-13;

j) IL-15; and

k) IFN-γ

.

6. A method for decreasing a T-cell activity in an individual suffering from acute graft-versus-host disease comprising administering to said individual an effective amount of a composition comprising an isolated antibody which specifically binds to the polypeptide consisting of SEQ ID NO:

39, wherein the antibody decreases a T-cell activity in vitro;

wherein decreasing a T-cell activity comprises one or more of;

decreasing T-cell proliferation;

decreasing gamma-IFN secretion by T-cells; and

decreasing the activation of CD8+ T-cells.

7. A method for decreasing a T-cell activity in an individual suffering from acute graft-versus-host disease comprising administering to said individual an effective amount of a composition comprising an isolated antibody which specifically binds to the polypeptide consisting of SEQ ID NO:

39, and a pharmaceutically acceptable carrier;

wherein the antibody decreases a T-cell activity in vitro, and

wherein decreasing a T-cell activity comprises one or more of;

decreasing T-cell proliferation;

decreasing gamma-IFN secretion by T-cells; and

decreasing the activation of CD8+ T-cells.

8. A method for decreasing a T-cell activity in an individual suffering from acute graft-versus-host disease comprising administering to said individual an effective amount of a composition comprising an isolated antibody which specifically binds to the polypeptide consisting of SEQ ID NO:

2, wherein the antibody decreases a T-cell activity in vitro, and

wherein decreasing a T-cell activity comprises one or more of;

decreasing T-cell proliferation;

decreasing gamma-IFN secretion by T-cells; and

decreasing the activation of CD8+ T-cells.

9. An isolated antibody which specifically binds to the polypeptide consisting of amino acid residues selected from the group consisting of:

a) amino acids 69-79 of SEQ ID NO;

2;

b) amino acids 85-94 of SEQ ID NO;

2;

c) amino acids 167-178 of SEQ ID NO;

2;

d) amino acids 184-196 of SEQ ID NO;

2; and

e) amino acids 221-233 of SEQ ID NO;

2.

10. A composition comprising the antibody of claim 9 and a pharmaceutically acceptable carrier.

11. A method for decreasing a T-cell activity in an individual suffering from acute graft-versus-host disease comprising administering to said individual an effective amount of a composition comprising the isolated antibody of claim 9 and a pharmaceutically acceptable carrier;

wherein the antibody decreases a T-cell activity in vitro, and wherein decreasing a T-cell activity comprises one or more of;

decreasing T-cell proliferation;

decreasing gamma-IFN secretion by T-cells; and

decreasing the activation of CD8+ T-cells.

12. An isolated antibody which specifically binds to a polypeptide consisting of amino acid residues selected from the group consisting of:

a) amino acids 13-20 of SEQ ID NO;

2; and

b) amino acids 23-36 of SEQ ID NO;

2.