Compositions and methods for diagnosing and treating asthma or other allergic or inflammatory diseases

• US 20040234517A1
• Filed: 03/04/2004
• Published: 11/25/2004
• Est. Priority Date: 03/04/2003
• Status: Abandoned Application

• Current Assignee: Wyeth (Pfizer Inc.)
• Original Assignee: Wyeth (Pfizer Inc.)
• Inventors: Chen, Hang, Liu, Wei, Follettie, Maximillian T., Williams, Cara, Ellis, Debra, Bowman, Michael R., Winkler, Aaron
• Application Number:
  US10/792,280
• Publication Number:
  US 20040234517A1
• Time in Patent Office: Days
• US Class Current: 424/94.63
• 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 11/00 Drugs for disorders of the respiratory system
• 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 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: C12N 15/113 Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing when used in plants C12N15/8218
• CPC Class Codes: C12N 15/1137 against enzymes viral enzymes C12N15/1131; receptors C12N15/1138
• CPC Class Codes: C12N 2310/14 interfering N.A.
• CPC Class Codes: C12Y 305/03001 Arginase (3.5.3.1)
• CPC Class Codes: G01N 2500/10 involving cells
• CPC Class Codes: G01N 2800/122 Chronic or obstructive airway disorders, e.g. asthma COPD
• CPC Class Codes: G01N 33/6893 related to diseases not provided for elsewhere

Abstract

The present invention provides compositions and methods useful for detecting or treating asthma or other allergic or inflammatory diseases. In one aspect, the methods of the present invention include inhibiting the activity or expression of a component of an arginine metabolic pathway in tissues affected by asthma or other allergic or inflammatory diseases. In many embodiments, the component being inhibited is a cationic amino acid transporter, an arginase, or a component downstream of the arginase. In many other embodiments, the activity or expression of the component is inhibited by an agent that binds to the component. In still many other embodiments, the activity or expression of the component is inhibited by an agent that binds a polynucleotide encoding the component.

Claims

1. A method comprising administering a therapeutically effective amount of an agent to a mammal which has an allergic or inflammatory disease, wherein said agent inhibits an activity or expression of a component of an arginine metabolic pathway in a tissue affected by the disease, and said component is not a nitric oxide synthase (NOS).

2. The method of claim 1, wherein the disease is a respiratory disease.

3. The method of claim 2, wherein the respiratory disease is asthma, chronic airway remodeling, or chronic obstructive pulmonary disease (COPD).

4. The method of claim 3, wherein said agent is capable of binding to the component or a polynucleotide encoding the component.

5. The method of claim 4, wherein said component is an arginase.

6. The method of claim 4, wherein said component is a cationic amino acid transporter.

7. The method of claim 4, wherein said component is downstream of an arginase in the pathway.

8. The method of claim 2, wherein said agent inhibits the expression of the component by RNA interference or an antisense mechanism.

9. The method of claim 8, wherein said agent encodes or comprises an siRNA capable of inhibiting the expression of ARG1 in said tissue by RNA interference.

10. The method of claim 8, wherein said agent encodes or comprises an siRNA capable of inhibiting the expression of CAT2 in said tissue by RNA interference.

11. The method of claim 2, wherein said agent is α

-difluoromethylornithine.

12. The method of claim 2, wherein said agent is lysine or a cationic polypeptide.

13. The method of claim 1, wherein the mammal is a human.

14. The method of claim 13, wherein said human has asthma or COPD, and said component is an arginase or a cationic amino acid transporter, and wherein said agent is capable of binding to said component or a polynucleotide encoding said component.

15. A method for identifying an agent for treating an allergic or inflammatory disease, comprising:

contacting a molecule with a tissue affected by asthma or another allergic or inflammatory disease, wherein said molecule is capable of binding to a non-NOS component of an arginine metabolic pathway or to a polynucleotide encoding said component; and

determining if said molecule is capable of ameliorating or eliminating a syndrome or phenotype associated with said asthma or disease.

16. The method of claim 15, wherein said molecule is selected or produced based on a structure-based rational drug design or based on screening a compound library.

17. The method of claim 15, wherein said component is an arginase or a cationic amino acid transporter.

18. A method, comprising:

detecting an expression profile of at least one gene in a biological sample of a mammal; and

comparing said expression profile to a reference expression profile of said at least one gene to determine if the mammal has or is at risk for an allergic or inflammatory disease,

wherein said one gene encodes a non-NOS component of an arginine metabolic pathway.

19. The method of claim 18, wherein the disease is asthma.

20. A pharmaceutical composition comprising a pharmaceutically-acceptable carrier and an agent capable of inhibiting an activity or expression of a non-NOS component of an arginine metabolic pathway.