Method of evaluating inflammatory skin disorders using IL-17 and/or IL-19

• US 7,427,402 B2
• Filed: 12/08/2006
• Issued: 09/23/2008
• 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 R., Kastelein, Robert A., McClanahan, Terrill K., Murphy, Erin
• Primary Examiner(s): Nickol; Gary
• Assistant Examiner(s): WOODWARD, CHERIE MICHELLE
• Application Number:
  US11/635,960
• Publication Number:
  US 20070098727A1
• Time in Patent Office: 655 Days
• Field of Search: None
• 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 non-lesional skin sample from the subject;

b) quantifying the level of IL-17A, IL-17F or IL-19 expression in the skin sample; and

c) comparing the level of IL-17A, IL-17F or IL-19 in the skin sample to the level in normal skin samples, wherein higher levels of expression of IL-17A, IL-17F or IL-19 than normal skin indicate a propensity of the subject to develop an inflammatory skin disorder.

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

3. The method of claim 1, wherein the level of IL-17A, IL-17F 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 level of IL-17A or IL-17F expression in the skin sample is at least 5-fold higher than normal skin.

7. The method of claim 1, wherein the level of IL-19 expression in the skin sample is at least 20-fold higher than normal 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. The method of claim 1, wherein the level of IL-17A or IL-17F expression in the skin sample is 2 to 50 fold higher than normal skin.

11. The method of claim 10, wherein the level of IL-17A or IL-17F expression in the skin sample is 5 to 20 fold higher than normal skin.

12. The method of claim 1, wherein the level of IL-19 expression in the skin sample is 5 to 130 fold higher than normal skin.