Use of IL-17 Expression to Predict Skin Inflammation; Methods of Treatment

• US 20090028860A1
• Filed: 09/02/2008
• Published: 01/29/2009
• Est. Priority Date: 05/03/2004
• Status: Active Grant

• Current Assignee: Merck Sharp & Dohme LLC (Merck & Co., Inc.)
• Original Assignee: Schering Corporation (Merck & Co., Inc.)
• Inventors: Kastelein, Robert A., McClanahan, Terrill K., Murphy, Erin
• Granted Patent: US 7,776,540 B2
• Time in Patent Office: Days
• US Class Current: 424/136.100
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• 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 37/02 Immunomodulators
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/158 Expression markers

Abstract

Provided are methods for diagnosing the propensity of a subject to develop skin inflammation, in particular, psoriasis. Also provided are methods of treatment with antagonists of IL-17 and/or IL-23.

Claims

1. A method of evaluating the propensity of a subject to develop an inflammatory skin disorder comprising:

a) obtaining a sample of skin from the subject; and

b) quantifying the level of IL-17 expression in the sample.

2. The method of claim 1, wherein the IL-17 expression is mRNA expression.

3. The method of claim 1, wherein the level of IL-17 expression is quantified by real-time PCR.

4. The method of claim 3, wherein the level of IL-17 expression is an average value between 5 and 20 fold higher than normal skin.

5. The method of claim 1, wherein the inflammatory skin disorder is cutaneous inflammation.

6. The method of claim 4, wherein the cutaneous inflammation is psoriasis.

7. The method of claim 1, wherein the skin sample is from non-lesional psoriatic skin.

8. The method of claim 1, wherein the subject has:

a) a family history of psoriasis;

or

b) previously presented psoriatic symptoms.

9. The method of claim 1, wherein the subject is a human.

10. A method of preventing skin inflammation comprising administering to a subject exhibiting a propensity to develop skin inflammation:

a) an antagonist of IL-17;

b) an antagonist of IL-23;

or

c) an antagonist of IL-17 and an antagonist of IL-23.

11. The method of claim 10, wherein the skin inflammation is cutaneous inflammation.

12. The method of claim 11, wherein the cutaneous inflammation is psoriasis.

13. The method of claim 10, wherein the subject expresses an average value of at least 5 fold higher IL-17 expression in a non-lesional psoriatic skin sample compared to a normal skin sample, as quantified by real-time PCR.

14. The method of claim 10, wherein the antagonist of IL-17 and/or IL-23 is an:

a) antibody or binding fragment thereof,

b) siRNA;

or

c) a small molecule inhibitor.

15. The method of claim 14, wherein the antibody is:

a) a polyclonal antibody;

b) a monoclonal antibody;

c) a humanized antibody;

d) a bi-specific antibody.