Use of cytokine expression to predict skin inflammation; methods of treatment

• US 20070098727A1
• Filed: 12/08/2006
• Published: 05/03/2007
• 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: Chan, Jason, McClanahan, Terrill, Murphy, Erin, Kastelein, Robert
• Granted Patent: US 7,427,402 B2
• Time in Patent Office: Days
• US Class Current: 424/145.1
• CPC Class Codes: A61K 31/713 Double-stranded nucleic acids or oligonucleotides
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• 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: C12Q 1/6881 for tissue or cell typing, e.g. human leukocyte antigen [HLA] probes
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/106 Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
• 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, IL-19, 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 or IL-19 expression in the sample.

2. The method of claim 1, wherein the IL-17 or IL-19 expression is mRNA expression.

3. The method of claim 1, wherein the level of IL-17 or IL-19 expression is quantified by real-time PCR.

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

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

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

7. The method of claim 6, wherein the level of IL-17 expression in the skin sample is an average value between 5 and 20 fold higher than normal skin.

8. The method of claim 6, wherein the level of IL-19 expression in the skin sample is an average value of between 5 and 130 fold higher than normal skin.

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

a) a family history of psoriasis;

or

b) previously presented psoriatic symptoms.

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

11. 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;

c) an antagonist of IL-19;

or

c) an antagonist of at least two cytokines selected from the group consisting of IL-17, IL-19, and IL-23.

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

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

14. The method of claim 11, 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.

15. The method of claim 11, wherein the subject expresses an average value of at least 20 fold higher IL-19 expression in a non-lesional psoriatic skin sample compared to a normal skin sample as quantified by real-time PCR.

16. The method of claim 11, wherein the antagonist of IL-17, IL-19, and/or IL-23 is an:

a) antibody or binding fragment thereof;

b) siRNA;

or

c) a small molecule inhibitor.

17. The method of claim 16, wherein the antibody is:

a) a polyclonal antibody;

b) a monoclonal antibody;

c) a humanized antibody;

d) a bi-specific antibody.