Manipulation of cytokine levels using CD83 gene products

• US 7,618,629 B2
• Filed: 11/21/2002
• Issued: 11/17/2009
• Est. Priority Date: 11/21/2001
• Status: Expired due to Fees

• Current Assignee: Celltech Group Limited (UCB SA)
• Original Assignee: Celltech Group Limited (UCB SA)
• Inventors: Proll, Sean C., Garcia-Martinez, Leon Fernando, Ramsdell, Fred, Appleby, Mark W., Staehling-Hampton, Karen
• Primary Examiner(s): Belyavskyi; Michail A
• Application Number:
  US10/496,284
• Publication Number:
  US 20060083740A1
• Time in Patent Office: 2,553 Days
• Field of Search: None
• US Class Current: 424/139.1
• 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 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 15/02 for disorders of the vagina
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 17/14 for baldness or alopecia
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 21/04 for myasthenia gravis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 27/14 Decongestants or antiallergics
• CPC Class Codes: A61P 27/16 Otologicals
• 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 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/06 for tuberculosis
• CPC Class Codes: A61P 31/12 : Antivirals
• CPC Class Codes: A61P 31/14 : for RNA viruses
• CPC Class Codes: A61P 31/16 : for influenza or rhinoviruses
• CPC Class Codes: A61P 31/18 : for HIV
• CPC Class Codes: A61P 31/22 : for herpes viruses
• CPC Class Codes: A61P 33/02 : Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
• CPC Class Codes: A61P 33/10 : Anthelmintics
• 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: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 : Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: C07K 14/70503 : Immunoglobulin superfamily
• CPC Class Codes: C07K 16/2803 : against the immunoglobulin superfamily
• CPC Class Codes: C07K 2317/56 : variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/565 : Complementarity determining region [CDR]
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The invention provides methods for modulating cytokine levels, GM-CSF levels and the immune system using CD83 nucleic acids, CD83 polypeptides, anti-CD83 antibodies and factors that influence CD83 activity or expression. The invention also provides mice having a mutant CD83 gene and mice having a transgenic CD83 gene, which are useful for defining the role of CD83 in the immune system and for identifying compounds that can modulate CD83 and the immune system.

Claims

1. An antibody that can bind to a CD83 polypeptide of SEQ ID NO:

9, wherein activated CD4⁺ T-cells produce lower levels of interleukin-4 when said T-cells are contacted with the antibody, wherein said antibody comprises a light chain and a heavy chain, and wherein the antibody comprises a light chain sequence set forth in SEQ ID NO;

58.

3. The antibody of claim 1, wherein the heavy chain variable region CDR1 of the antibody comprises the sequence SYDMT (SEQ ID NO:

23).

9. An antibody according to any one of claims 1-2, 3-8 or wherein the antibody is a polyclonal antibody.

10. An antibody according to any one of claims 1-2, 3-8 or wherein the antibody is a monoclonal antibody.

11. The antibody of claim 1, wherein the heavy chain variable region CDR2 of the antibody comprises the sequence YASGSTYY (SEQ ID NO:

27).

12. The antibody of claim 1, wherein the heavy chain variable region CDR3 of the antibody comprises the sequence EHAGYSGDTGH (SEQ ID NO:

32).

13. The antibody of claim 1, wherein the heavy chain variable region comprises one or more of the CDR1 of the antibody comprising sequence SYDMT (SEQ ID NO:

23), the CDR2 of the antibody comprising sequence YASGSTYY (SEQ ID NO;

27) or the CDR3 of the antibody comprising sequence EHAGYSGDTGH (SEQ ID NO;

32).

2. An antibody that can bind to a CD83 polypeptide of SEQ ID NO:

9, wherein CD4⁺ T-cell proliferation is decreased when said T-cells are contacted with the antibody, wherein said antibody comprises a light chain and a heavy chain, and wherein the antibody comprises a light chain sequence set forth in SEQ ID NO;

58.

14. The antibody of claim 2, wherein the heavy chain variable region CDR1 of the antibody comprises the sequence SYDMT (SEQ ID NO:

23).

15. The antibody of claim 2, wherein the heavy chain variable region CDR2 of the antibody comprises the sequence YASGSTYY (SEQ ID NO:

27).

16. The antibody of claim 2, wherein the heavy chain variable region CDR3 of the antibody comprises the sequence EHAGYSGDTGH (SEQ ID NO:

32).

17. The antibody of claim 2, wherein the heavy chain variable region comprises one or more of the CDR1 of the antibody comprising sequence SYDMT (SEQ ID NO:

23), the CDR2 of the antibody comprising sequence YASGSTYY (SEQ ID NO;

27) or the CDR3 of the antibody comprising sequence EHAGYSGDTGH (SEQ ID NO;

32).

4. An antibody that can bind to a CD83 polypeptide of SEQ ID NO:

9, wherein activated CD4⁺ T-cells produce lower levels of interleukin-4 when said T-cells are contacted with the antibody, wherein said antibody comprises a light chain and a heavy chain, and wherein the antibody comprises the heavy chain sequence set forth in SEQ ID NO;

60.

18. The antibody of claim 4 wherein the light chain variable region CDR1 of the antibody comprises the sequence RCAYD (SEQ ID NO:

37).

19. The antibody of claim 4 wherein the light chain variable region CDR2 of the antibody comprises the sequence OSISTY (SEQ ID NO:

40.

20. The antibody of claim 4 wherein the light chain variable region CDR3 of the antibody comprises the sequence QQGYTHSNVDNV (SEQ ID NO:

44).

21. The antibody of claim 4, wherein the light chain variable region comprises one or more of the CDR1 of the antibody comprising sequence RCAYD (SEQ ID NO:

37), the CDR2 of the antibody comprising sequence OSISTY (SEQ ID NO;

40, or the CDR3 of the antibody comprising sequence QQGYTHSNVDNV (SEQ ID NO;

44).

22. The antibody of claim 4, wherein the light chain comprises the sequence set forth in SEQ ID NO:

58.

5. An antibody that can bind to a CD83 polypeptide of SEQ ID NO:

9, wherein CD4⁺ T-cell proliferation is decreased when said T-cells are contacted with the antibody, wherein said antibody comprises a light chain and a heavy chain, and wherein the antibody comprises the heavy chain sequence set forth in SEQ ID NO;

60.

23. The antibody of claim 5 wherein the light chain variable region CDR1 of the antibody comprises the sequence RCAYD (SEQ ID NO:

37).

24. The antibody of claim 5 wherein the light chain variable region CDR2 of the antibody comprises a-the sequence OSISTY (SEQ ID NO:

40.

25. The antibody of claim 5 wherein the light chain variable region CDR3 of the antibody comprises the sequence QQGYTHSNVDNV (SEQ ID NO:

44).

26. The antibody of claim 5, wherein the light chain variable region comprises one or more of the CDR1 of the antibody comprising sequence RCAYD (SEQ ID NO:

37);

the CDR2 of the antibody comprising sequence OSISTY (SEQ ID NO;

40 or the CDR3 of the antibody comprising sequence QQGYTHSNVDNV (SEQ ID NO;

44).

27. The antibody of claim 5, wherein the light chain comprises the sequence set forth in SEQ ID NO:

58.

6. An antibody that modulates the activity or expression of a CD83 polypeptide of SEQ ID NO:

9, wherein said antibody comprises a light chain and a heavy chain, and wherein the antibody comprises the heavy chain sequence set forth in SEQ ID NO;

60.

7. An antibody according to claim 6 comprising a light chain variable region comprising a CDR1 sequence of RCAYD (SEQ ID NO:

37).

8. An antibody according to claim 6, wherein the light chain comprises the sequence of SEQ ID NO:

58.

28. An antibody according to claim 6 comprising a light chain variable region comprising a CDR2 sequence of OSISTY (SEQ ID NO:

40).

29. An antibody according to claim 6 comprising a light chain variable region comprising a CDR3 sequence of QQGYTHSNVDNV (SEQ ID NO:

44).

30. The antibody of claim 6, wherein the light chain variable region comprises one or more of the CDR1 of the antibody comprising sequence RCAYD (SEQ ID NO:

37);

the CDR2 of the antibody comprising sequence OSISTY (SEQ ID NO;

40 or the CDR3 of the antibody comprising sequence QQGYTHSNVDNV (SEQ ID NO;

44).

31. An antibody that modulates the activity or expression of a CD83 polypeptide of SEQ ID NO:

9, wherein said antibody comprises a light chain and a heavy chain, and wherein the antibody comprises the light chain sequence set forth in SEQ ID NO;

58.

32. The antibody of claim 31, wherein the heavy chain variable region CDR1 of the antibody comprises the sequence SYDMT (SEQ ID NO:

23).

33. The antibody of claim 31, wherein the heavy chain variable region CDR2 of the antibody comprises the sequence YASGSTYY (SEQ ID NO:

27).

34. The antibody of claim 31, wherein the heavy chain variable region CDR3 of the antibody comprises the sequence EHAGYSGDTGH (SEQ ID NO:

32).

35. The antibody of claim 31, wherein the heavy chain variable region comprises one or more of the CDR1 of the antibody comprising sequence SYDMT (SEQ ID NO:

23), the CDR2 of the antibody comprising sequence YASGSTYY (SEQ ID NO;

27) or the CDR3 of the antibody comprising sequence EHAGYSGDTGH (SEQ ID NO;

32).