Compositions and methods for the treatment and diagnosis of immune disorders

• US 20090041752A1
• Filed: 07/31/2007
• Published: 02/12/2009
• Est. Priority Date: 03/03/1995
• Status: Abandoned Application

• Current Assignee: Millennium Pharmaceuticals Incorporated (Takeda Pharmaceutical Company Limited)
• Original Assignee: Millennium Pharmaceuticals Incorporated (Takeda Pharmaceutical Company Limited)
• Inventors: McCarthy, Sean A., Levinson, Douglas Adam, Lloyd, Clare M.
• Application Number:
  US11/888,354
• Publication Number:
  US 20090041752A1
• Time in Patent Office: Days
• US Class Current: 424/130.100
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 31/08 for leprosy
• CPC Class Codes: A61P 33/02 Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07K 14/47 from mammals

Abstract

The present invention relates to methods and compositions for the treatment and diagnosis of immune disorders, especially T helper lymphocyte-related disorders, and also for the treatment of mast cell-related processes and disorders, ischemic disorders and injuries, including ischemic renal disorders and injuries. For example, genes which are differentially expressed within and among T helper (TH) cells and TH cell subpopulations, which include, but are not limited to TH0, TH1 and TH2 cell subpopulations are identified. Genes are also identified via the ability of their gene products to interact with gene products involved in the differentiation, maintenance and effector function of such TH cells and TH cell subpopulations. The genes identified can be used diagnostically or as targets for therapeutic intervention. In this regard, the present invention provides methods for the identification and therapeutic use of compounds as treatments of immune disorders, especially TH cell subpopulation-related disorders. Additionally, methods are provided for the diagnostic evaluation and prognosis of TH cell subpopulation-related disorders, for the identification of subjects exhibiting a predisposition to such conditions, for monitoring patients undergoing clinical evaluation for the treatment of such disorders, and for monitoring the efficacy of compounds used in clinical trials. Methods are also provided for the treatment of symptoms associated with mast cell-related processes or disorders and ischemic disorders and injuries using the genes, gene products and antibodies of the invention.

Claims

1. A method for ameliorating a symptom of an ischemic disorder or injury in a mammal, comprising administering to the mammal a 200 gene product in an amount effective to ameliorate the symptom of the ischemic disorder or injury.

4. The method of claim 1, wherein the ischemic disorder or injury is an ischemic renal disease, a myocardial ischemia, an infarction, or an ischemic injury to a transplanted organ.

10. The method of claim 1, wherein the 200 gene product is a polypeptide comprising:

(a) the amino acid sequence of SEQ ID NO;

10,

(b) the amino acid sequence encoded by the nucleotide sequence of SEQ ID NO;

8,

(c) the amino acid sequence encoded by the cDNA insert of the clone E. coli DH10B(Zip)™

containing 200-P (NRRL Accession No. B-21415), 200-AF (NRRL Accession No. B-21457), or 200-0 (NRRL Accession No. B-21395),

(d) the amino acid sequence of SEQ ID NO;

24,

(e) the amino acid sequence encoded by the nucleotide sequence of SEQ ID NO;

37, or

(f) the amino acid sequence encoded by the cDNA insert of the clone feht200C (ATCC Accession No.

     69967).

11. The method of claim 1, wherein the 200 gene product is a polypeptide encoded by a nucleic acid molecule which hybridizes under highly stringent conditions to the complement of:

(a) a nucleic acid molecule which encodes the amino acid sequence of SEQ ID NO;

10;

(b) a nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO;

8,

(c) the cDNA sequence contained in the clone E. coli DH10B(Zip)™

containing 200-P (NRRL Accession No. B-21415), 200-AF (NRRL Accession No. B-21457), or 200-0 (NRRL Accession No. B-21395),

(d) to the complement of a nucleic acid molecule which encodes the amino acid sequence of SEQ ID NO;

24,

(e) to the complement of the nucleotide sequence of SEQ ID NO;

37, or

(f) to the complement of the cDNA sequence contained in the clone feht200C (ATCC Accession No.

     69967).

13. The method of claim 1, wherein said administering of the 200 gene product is parenteral, subcutaneous, intraperitoneal, intrapulmonary, intranasal, or intralesional.

28. The method of claim 1, wherein the ischemic disorder or injury is angina pectoris, a myocardial infarction, or a cortical infarction.

2. A method for ameliorating a symptom of an ischemic disorder or injury in a mammal, comprising administering to the mammal a nucleic acid molecule encoding a 200 gene product in an amount effective to ameliorate the symptom of the ischemic disorder or injury.

12. The method of claim 2, wherein the nucleic acid molecule encoding a gene 200 product comprises:

(a) a nucleotide sequence which encodes the amino acid sequence of SEQ ID NO;

10,

(b) the nucleotide sequence of SEQ ID NO;

8,

(c) the nucleotide sequence of the cDNA insert of the clone E. coli DH10B(Zip)™

containing 200-P (NRRL Accession No. B-21415), 200-AF (NRRL Accession No. B-21457), or 200-0 (NRRL Accession No. B-21395),

(d) a nucleotide sequence which encodes the amino acid sequence of SEQ ID NO;

24,

(e) the nucleotide sequence of SEQ ID NO;

37, or

(f) the nucleotide sequence of the cDNA insert of the clone feht200c (ATCC Accession No.

     69967).

15. The method of claim 2, wherein said administering of the nucleic acid is parenteral, subcutaneous, intraperitoneal, intrapulmonary, intranasal, or intralesional.

22. The method of claim 2, wherein the ischemic disorder or injury is an ischemic renal disease, a myocardial ischemia, an infarction, or an ischemic injury to a transplanted organ.

24. The method of claim 2, wherein the 200 gene product is a polypeptide comprising:

(a) the amino acid sequence of SEQ ID NO;

10,

(b) the amino acid sequence encoded by the nucleotide sequence of SEQ ID NO;

8,

(c) the amino acid sequence encoded by the cDNA insert of the clone E. coli DH10B(Zip)™

containing 200-P (NRRL Accession No. B-21415), 200-AF (NRRL Accession No. B-21457), or 200-0 (NRRL Accession No. B-21395),

(d) the amino acid sequence of SEQ ID NO;

24,

(e) the amino acid sequence encoded by the nucleotide sequence of SEQ ID NO;

37, or

(f) the amino acid sequence encoded by the cDNA insert of the clone feht200C (ATCC Accession No.

     69967).

26. The method of claim 2, wherein the 200 gene product is a polypeptide encoded by a nucleic acid molecule which hybridizes under highly stringent conditions to the complement of:

(a) a nucleic acid molecule which encodes the amino acid sequence of SEQ ID NO;

10;

(b) a nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO;

8,

(c) the cDNA sequence contained in the clone E. coli DH10B(Zip)™

containing 200-P (NRRL Accession No. B-21415), 200-AF (NRRL Accession No. B-21457), or 200-0 (NRRL Accession No. B-21395),

(d) to the complement of a nucleic acid molecule which encodes the amino acid sequence of SEQ ID NO;

24,

(e) to the complement of the nucleotide sequence of SEQ ID NO;

37, or

(f) to the complement of the cDNA sequence contained in the clone feht200C (ATCC Accession No.

     69967).

29. The method of claim 2, wherein the ischemic disorder or injury is angina pectoris, a myocardial infarction, or a cortical infarction.

3. A method for ameliorating a symptom of a ischemic disorder or injury in a mammal, comprising administering to the mammal an antibody directed against a 200 gene product in an amount effective to ameliorate the symptom of the disorder.

17. The method of claim 3, wherein said administering of the antibody is parenteral, subcutaneous, intraperitoneal, intrapulmonary, intranasal, or intralesional.

19. The method of claim 3, wherein the amount of the antibody administered is from about 1 μ

g/kg to about 100 mg/kg.

23. The method of claim 3, wherein the ischemic disorder or injury is an ischemic renal disease, a myocardial ischemia, an infarction, or an ischemic injury to a transplanted organ.

25. The method of claim 3, wherein the 200 gene product is a polypeptide comprising:

(a) the amino acid sequence of SEQ ID NO;

10,

(b) the amino acid sequence encoded by the nucleotide sequence of SEQ ID NO;

8,

(c) the amino acid sequence encoded by the cDNA insert of the clone E. coli DH10B(Zip)™

containing 200-P (NRRL Accession No. B-21415), 200-AF (NRRL Accession No. B-21457), or 200-0 (NRRL Accession No. B-21395),

(d) the amino acid sequence of SEQ ID NO;

24,

(e) the amino acid sequence encoded by the nucleotide sequence of SEQ ID NO;

37, or

(f) the amino acid sequence encoded by the cDNA insert of the clone feht200C (ATCC Accession No.

     69967).

27. The method of claim 3, wherein the 200 gene product is a polypeptide encoded by a nucleic acid molecule which hybridizes under highly stringent conditions to the complement of:

(a) a nucleic acid molecule which encodes the amino acid sequence of SEQ ID NO;

10;

(b) a nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO;

8,

(c) the cDNA sequence contained in the clone E. coli DH10B(Zip)™

containing 200-P (NRRL Accession No. B-21415), 200-AF (NRRL Accession No. B-21457), or 200-0 (NRRL Accession No. B-21395),

(d) to the complement of a nucleic acid molecule which encodes the amino acid sequence of SEQ ID NO;

24,

(e) to the complement of the nucleotide sequence of SEQ ID NO;

37, or

(f) to the complement of the cDNA sequence contained in the clone feht200C (ATCC Accession No.

     69967).

30. The method of claim 3, wherein the ischemic disorder or injury is angina pectoris, a myocardial infarction, or a cortical infarction.

5-9. -9. (canceled)

14. (canceled)

16. (canceled)

18. (canceled)

20-21. -21. (canceled)