Compositions and methods for the treatment and diagnosis of immune disorders

• US 7,172,750 B2
• Filed: 09/20/2002
• Issued: 02/06/2007
• Est. Priority Date: 03/03/1995
• Status: Expired due to Term

• Current Assignee: Millennium Pharmaceuticals Incorporated (Takeda Pharmaceutical Company Limited)
• Original Assignee: Millennium Pharmaceuticals Incorporated (Takeda Pharmaceutical Company Limited)
• Inventors: Levinson, Douglas Adam
• Primary Examiner(s): Swartz; Rodney P
• Application Number:
  US10/252,131
• Publication Number:
  US 20030158399A1
• Time in Patent Office: 1,600 Days
• Field of Search: 424/9.1, 424/9.2, 424/130.1, 424/139.1, 435/8, 536/22.1, 536/23.1, 536/23.4
• US Class Current: 424/9.2
• CPC Class Codes: A01K 2207/15 Humanized animals
• CPC Class Codes: A01K 2217/00 Genetically modified animals
• CPC Class Codes: A01K 2217/05 Animals comprising random inserted nucleic acids (transgenic)
• CPC Class Codes: A01K 2217/052 inducing gain of function
• CPC Class Codes: A01K 2217/206 Animal model comprising tissue-specific expression system, e.g. tissue specific expression of transgene, of Cre recombinase
• CPC Class Codes: A01K 2217/30 Animal model comprising expression system for selective cell killing, e.g. toxins, enzyme dependent prodrug therapy using ganciclovir
• CPC Class Codes: A01K 2227/105 Murine
• CPC Class Codes: A01K 2227/50 Amphibians, e.g. Xenopus
• CPC Class Codes: A01K 2267/03 Animal model, e.g. for test or diseases
• CPC Class Codes: A01K 2267/0325 Animal model for autoimmune diseases
• CPC Class Codes: A01K 2267/0368 Animal model for inflammation
• CPC Class Codes: A01K 2267/0381 Animal model for diseases of the hematopoietic system
• CPC Class Codes: A01K 2267/0387 Animal model for diseases of the immune system
• CPC Class Codes: A01K 67/0275 Genetically modified vertebrates, e.g. transgenic
• CPC Class Codes: A01K 67/0278 Knock-in vertebrates, e.g. humanised vertebrates
• 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 11/06 Antiasthmatics
• 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 3/08 for glucose homeostasis pancreatic hormones A61P5/48
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/04 : Antibacterial agents
• CPC Class Codes: A61P 37/00 : Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: B60G 13/003 : characterised by the mounting on the vehicle body or chassis of the damper unit
• CPC Class Codes: C07K 14/70503 : Immunoglobulin superfamily
• CPC Class Codes: C07K 16/2803 : against the immunoglobulin superfamily
• CPC Class Codes: C07K 19/00 : Hybrid peptides , i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
• CPC Class Codes: C07K 2319/00 : Fusion polypeptide
• CPC Class Codes: C12N 15/8509 : for producing genetically modified animals, e.g. transgenic
• CPC Class Codes: C12N 2800/30 : Vector systems comprising sequences for excision in presence of a recombinase, e.g. loxP or FRT
• CPC Class Codes: C12N 2830/00 : Vector systems having a special element relevant for transcription
• CPC Class Codes: C12N 9/6467 : Granzymes, e.g. granzyme A (3.4.21.78); granzyme B (3.4.21.79)
• CPC Class Codes: C12N 9/6472 : Cysteine endopeptidases (3.4.22)
• CPC Class Codes: C12Q 1/6809 : Methods for determination or identification of nucleic acids involving differential detection
• 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
• CPC Class Codes: Y10S 424/81 : involving autoimmunity, allergy, immediate hypersensitivity, delayed hypersensitivity, immunosuppression, immunotolerance, or anergy
• CPC Class Codes: Y10S 530/868 : involving autoimmunity, allergy, immediate hypersensitivity, delayed hypersensitivity, immunosuppression, or immunotolerance

Abstract

The present invention relates to methods and compositions for the treatment and diagnosis of immune disorders, especially T helper lymphocyte-related disorders. 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.

Claims

1. A method of treating asthma, allergy, or allergic rhinitis in a subject comprising administering to the subject a therapeutically effective amount of a compound that modulates a TH mediated immune response involved in causing said asthma, allergy, or allergic rhinitis so that symptoms of said asthma, allergy, or allergic rhinitis are ameliorated, wherein the compound is:

(i) a soluble polypeptide comprising the extracellular domain of a 200 gene product;

(ii) a soluble polypeptide comprising the Ig type variable set domain of a 200 gene product;

or

(iii) a fusion protein comprising the soluble polypeptide of (i) or (ii) above.

2. The method of claim 1, wherein a TH1 mediated immune response is increased.

3. The method of claim 1 or 2, wherein a TH2 mediated immune response is decreased.

4. The method of claim 1, wherein the compound is a fusion protein comprising a soluble polypeptide comprising the extracellular domain of a 200 gene product or a soluble polypeptide comprising the Ig type variable set domain of a 200 gene product and an Ig tail.

5. The method of claim 4, wherein the fusion protein comprises the extracellular domain of a 200 gene product and an IgFc.

6. The method of claim 1 or 2, wherein the subject is a human.

7. The method of claim 1, wherein the compound is a soluble polypeptide comprising the extracellular domain of a 200 gene product.

8. The method of claim 6, wherein the 200 gene product is a human 200 gene product.

9. The method of claim 8, wherein the human 200 gene product has the amino acid sequence depicted in FIG. 24 (SEQ ID NO:

24).

10. The method of claim 1, wherein the compound is administered orally, by inhalation, intravenously or intramuscularly.

20. The method of claim 1, wherein the compound is a soluble polypeptide comprising the Ig type variable set domain of a 200 gene product.

11. A method of treating asthma, allergy, or allergic rhinitis in a subject comprising administering to the subject a therapeutically effective amount of a compound that modulates a TH mediated immune response involved in causing said asthma, allergy, or allergic rhinitis so that symptoms of said asthma, allergy, or allergic rhinitis are ameliorated, wherein the compound is an antibody or fragment thereof which specifically binds the extracellular domain of a 200 gene product.

12. The method of claim 11, wherein a TH1 mediated immune response is increased.

13. The method of claim 11 or 12, wherein a TH2 mediated immune response is decreased.

14. The method of claim 11, wherein the antibody or fragment thereof is a polyclonal antibody, monoclonal antibody, humanized antibody, chimeric antibody, single chain antibody, a Fab fragment, a F(ab′

) 2 fragment, or an epitope-binding fragment of any of the foregoing.

15. The method of claim 11, wherein the antibody or fragment thereof specifically binds to the Ig type variable set domain of a 200 gene product.

16. The method of claim 11 or 12, wherein the subject is a human.

17. The method of claim 16, wherein the 200 gene product is a human 200 gene product.

18. The method of claim 17, wherein the human 200 gene product has the amino acid sequence depicted in FIG. 24 (SEQ ID NO:

24).

19. The method of claim 11, wherein the compound is administered orally, by inhalation, intravenously or intramuscularly.