Apoptosis inducing molecule II and methods of use

• US 6,635,743 B1
• Filed: 03/10/2000
• Issued: 10/21/2003
• Est. Priority Date: 03/22/1996
• Status: Expired due to Term

• Current Assignee: Human Genome Sciences Incorporated (GlaxoSmithKline PLC)
• Original Assignee: Human Genome Sciences Incorporated (GlaxoSmithKline PLC)
• Inventors: Ullrich, Stephen, Zhai, Yifan, Yu, Guo-Liang, Ebner, Reinhard, Ruben, Steven M.
• Primary Examiner(s): Romeo, David S.
• Application Number:
  US09/523,323
• Time in Patent Office: 1,320 Days
• Field of Search: 530/387.1, 530/387.3, 530/388.1, 530/388.23, 530/389.1, 530/389.2, 435/7.1, 930/144
• US Class Current: 530/388.23
• 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 2317/73 Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
• 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
• CPC Class Codes: Y10S 930/144 Tumor necrosis factor

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. An isolated antibody or portion thereof that binds to a protein selected from the group consisting of:

a) a protein whose sequence consists of an immunogenic fragment of the amino acid residues 68-240 of SEQ ID NO;

2;

b) a protein whose sequence consists of a fragment of amino acids residues 68-240 of SEQ ID NO;

2, wherein said fragment comprises at least 30 animo acid residues; and

c) a protein whose sequence consists of a fragment of amino acid residues 68-240 of SEQ ID NO;

2 wherein said fragment comprises at least 50 amino acids.

2. The antibody or portion thereof of claim 1 which is a monoclonal antibody.

3. The antibody or portion thereof of claim 1 which is a polyclonal antibody.

4. The antibody or portion thereof of claim 1 which is a chimeric antibody.

5. The antibody or portion thereof of claim 1 which is a single chain antibody.

6. The antibody or portion thereof of claim 1 which is a Fab fragment.

7. An isolated cell that produces the antibody of claim 1.

8. A hybridoma that produces the antibody of claim 1.

9. A method of detecting in a biological sample a protein that binds the antibody or portion thereof of claim 1 comprising:

(a) contacting the biological sample with the antibody or portion thereof; and

(b) detecting the protein in the biological sample.

10. A composition comprising the antibody or portion thereof of claim 1 and a carrier.

11. A hybridoma that produces the antibody of claim 5.

12. The method of claim 9 wherein the antibody is a monoclonal antibody.

13. The method of claim 9 wherein the antibody is a polyclonal antibody.

14. The method of claim 9 wherein the antibody is a chimeric antibody.

15. The composition of claim 10, wherein the antibody or portion thereof is a monoclonal antibody.

16. The composition of claim 10, wherein the antibody or portion thereof is a chimeric antibody.

17. The composition of claim 10, wherein the antibody or portion thereof is a single chain antibody.

18. The composition of claim 10, wherein the antibody or portion thereof is a Fab fragment.

19. An isolated antibody or portion thereof produced by immunizing an animal with a protein selected from the group consisting of:

a) a protein whose sequence consists of an immunogenic fragment of the amino acid residues 68-240 of SEQ ID NO;

2;

b) a protein whose sequence consists of a fragment of amino acids residues 68-240 of SEQ ID NO;

2, wherein said fragment comprises at least 30 amino acid residues; and

c) a protein whose sequence consists of a fragment of amino acids residues 68-240 of SEQ ID NO;

2 wherein said fragment comprises at least 50 amino acids;

wherein said antibody or portion thereof binds the protein of a), b), or c).

20. A method of detecting in a biological sample a protein that binds the antibody or portion thereof of claim 19 comprising:

(a) contacting the biological sample with the antibody or portion thereof; and

(b) detecting the protein in the biological sample.

21. A composition comprising the antibody or portion thereof of claim 19 and a carrier.

22. The method of claim 20 wherein the antibody is a monoclonal antibody.

23. The method of claim 20 wherein the antibody is a polyclonal antibody.

24. The method of claim 20 wherein the antibody is a chimeric antibody.

25. The method of claim 20 wherein the antibody is a humanized antibody.

26. The method of claim 20 wherein the antibody is a single chain antibody.

27. The composition of claim 21, wherein the antibody or portion thereof is a monoclonal antibody.

28. The composition of claim 21, wherein the antibody or portion thereof is a chimeric antibody.

29. The composition of claim 21, wherein the antibody or portion thereof is a single chain antibody.

30. The composition of claim 21, wherein the antibody or portion thereof is a Fab fragment.

31. An isolated antibody or portion thereof that binds to a protein whose sequence consists of amino acid residues 68 to 240 of SEQ ID NO:

2.

32. The antibody or portion thereof of claim 31 which is a monoclonal antibody.

33. The antibody or portion thereof of claim 31 which is a polyclonal antibody.

34. The antibody or portion thereof of claim 31 which is a chimeric antibody.

35. The antibody or portion thereof of claim 31 which is a single chain antibody.

36. The antibody or portion thereof of claim 31 which is a Fab fragment.

37. An isolated cell that produces the antibody of claim 31.

38. A hybridoma that produces the antibody of claim 31.

39. A hybridoma that produces the antibody of claim 31.