Il-21 as a regulator of immunoglobin production
(19)AUSTRALIAN PATENT OFFICE (54) Title 11-21 as a regulator of immunoglobin production (51)6 International Patent Classification(s) A01K 067/027 C12Q 001/68 G01N 033/53 (21) Application No: 2003251633 (22) Application Date: 2003 .06.26 (87) WIPO No: WO04/003156 (30) Priority Data (31) Number (32) Date 60/393,215 2002.07.01 (33) Country US 200511037 (43) (43) Publication Date : 2004 .01.19 Publication Journal Date : 2004 .03.04 (71) Applicant(s) THE GOVERNMENT OF THE UNITED STATES OF AMERICA as represented by THE SECRETARY OF THE DEPARTMENT OF (72) Inventor(s) Ozaki, Katsutoshi; Leonard, Warren J.; Spolski, Rosanne(-1-1) Application NoAU2003251633 A8(19)AUSTRALIAN PATENT OFFICE (54) Title 11-21 as a regulator of immunoglobin production (51)6 International Patent Classification(s) A01K 067/027 C12Q 001/68 G01N 033/53 (21) Application No: 2003251633 (22) Application Date: 2003 .06.26 (87) WIPO No: WO04/003156 (30) Priority Data (31) Number (32) Date 60/393,215 2002.07.01 (33) Country US 200511037 (43) (43) Publication Date : 2004 .01.19 Publication Journal Date : 2004 .03.04 (71) Applicant(s) THE GOVERNMENT OF THE UNITED STATES OF AMERICA as represented by THE SECRETARY OF THE DEPARTMENT OF (72) Inventor(s) Ozaki, Katsutoshi; Leonard, Warren J.; Spolski, Rosanne-1- A transgenic mouse is disclosed herein whose somatic and germ cells comprise a disrupted IL-21 receptor gene, the disruption being sufficient to inhibit the binding of IL-21 to an IL-21 receptor, and a disrupted IL-4 gene, the disruption being sufficient to inhibit the production of IL-4 or the binding of IL-4 to the IL-4 receptor. A mouse homozygous for the disrupted IL-21 receptor gene and homozygous for the disrupted IL-4 gene has diminished B cell function. A method is disclosed for altering a B cell activity. The method includes administering a therapeutically effective amount of an agent that interferes with the interaction of IL-21 with an IL-21 receptor, thereby altering the B cell activity. A method is also disclosed for of treating a subject with Job's disorder or atopic disease. A method is also disclosed for treating or preventing an allergic reaction in a subject. A method is also disclosed for treating a subject with an autoimmune or antibody mediated disorder. CLAIMSWe claim:1. A transgenic mouse whose somatic and germ cells comprise a disrupted IL-21 receptor gene, the disruption being sufficient to inhibit the binding of IL-21 to an IL-21 receptor, and a disrupted IL-4 gene, the disruption being sufficient to inhibit the production of IL-4 or the binding of IL-4 to the IL-4 receptor, the disrupted IL-21 receptor and IL-4 genes being introduced into the mouse or an ancestor of the mouse at an embryonic stage, wherein a mouse homozyogous for the disrupted IL-21 receptor gene and homozygous for the disrupted IL-4 gene has diminished B cell function.
2. The transgenic mouse of claim 1, wherein the mouse has panhypogammaglobulinemia.
3. The transgenic mouse of claim 1, wherein the mouse is deficient in the production of an immunoglobulin.
4. The transgenic mouse of claim 3, wherein the immunoglobulin is an IgG.
5. The transgenic mouse of claim 4, wherein the IgG is an IgGl, IgGl, IgG2a, IgG2b, or IgG3.
6. The transgenic mouse of claim 3, wherein the immunoglobulin is IgE.
7. A transgenic mouse whose genome is heterozygous for an engineered disruption in an IL-21 receptor gene and whose genome is heterozygous for an engineered disruption in an IL-4 gene, wherein the engineered IL-21 receptor gene and the engineered IL-4 gene in a homozygous state inhibits production of a functional IL-21 receptor and a functional IL-4, wherein the transgenic mouse is deficient for production of an immunoglobulin. <Desc/Clms Page number 60> 8. The transgenic mouse of claim 7, wherein the immunoglobulin is an IgG.
9. The transgenic mouse of claim 8, wherein the IgG is an IgGl, IgGl, IgG2a, IgG2b, or IgG3.
10. The transgenic mouse of claim 7, wherein the immunoglobulin is an IgE.
11. A method of altering a B cell activity, comprising contacting an effective amount of an agent that interferes with the interaction of IL-21 with an IL-21 receptor, thereby altering the B cell activity.
12. The method of claim 11, wherein the B cell activity is production of an immunoglobulin.
13. The method of claim 12, wherein the immunoglobulin is an IgG or an IgE.
14. The method of claim 13, wherein the IgG is an IgGl, IgG2a, IgG2b, or an IgG3.
15. The method of claim 11, wherein the agent is an antagonist of the IL-21 receptor, a soluble IL-21 receptor, or a small molecule that binds the IL-21 receptor.
16. The method of claim 11, wherein the agent is an antibody that specifically binds IL-21 and inhibits the interaction of IL-21 with its receptor.
17. The method of claim 11, wherein the agent is an antisense nucleic acid, a small inhibitory RNA, or a ribozyme that specifically binds a nucleic acid encoding the IL-21 receptor. <Desc/Clms Page number 61> 18. The method of claim 11, further comprising contacting the cell with an effective amount of an agent that interferes with the interaction of IL-4 with an IL-4 receptor.
19. The method of claim 18, wherein the agent is an antagonist of the IL-4 receptor, a soluble IL-4 receptor, or a small molecule that binds the IL-4 receptor.
20. The method of claim 18, wherein the agent is an antibody that specifically binds IL-4 and inhibits the interaction of IL-4 with its receptor.
21. The method of claim 18, wherein the agent is an antisense nucleic acid, a small inhibitory RNA, or a ribozyme that specifically binds a nucleic acid encoding the IL-4 receptor.
22. The method of claim 11, wherein the B cell is in vitro.
23. The method of claim 11, wherein the B cell is in a subject.
24. The method of claim 23, wherein the subject has an allergic reaction.
25. The method of claim 23, wherein the subject has an autoimmune disorder.
26. A method of treating a subject with Job's disorder or atopic disease, comprising administering to the subject a therapeutically effective amount of IL-21 or an agonist thereof, thereby ameliorating a sign or a symptom of Job's disorder or atopic disease.
27. The method of claim 26, wherein the agonist is a small molecule that binds the IL-21 receptor. <Desc/Clms Page number 62> 29. The method of claim 28, wherein the agent is an antagonist of the IL-21 receptor, a soluble IL21 receptor, or a small molecule that binds the IL-21 receptor.
30. The method of claim 28, wherein the agent is an antibody that specifically binds IL-21 and inhibit s the interaction of IL-21 with its receptor.
31. The method of claim 28, wherein the agent is an antisense nucleic acid, a small inhibitory RNA, or a ribozyme that specifically binds a nucleic acid encoding the IL-21 receptor.
32. The method of claim 28, further comprising administering to the subject a therapeutically effective amount of an agent that inhibits the interaction of IL-4 with its receptor.
33. The method of claim 32, wherein the agent is an antagonist of the IL-4 receptor, a soluble IL-4 receptor, or a small molecule that binds the IL-4 receptor.
34. The method of claim 32, wherein the agent is an antibody that specifically binds IL-4 and inhibit s the interaction of IL-4 with its receptor.
35. The method of claim 32, wherein the agent is an antisense nucleic acid, a small inhibitory RNA, or a ribozyme that specifically binds a nucleic acid encoding the IL-4 receptor.