Methods for assessing response to therapy in subjects having ulcerative colitis

• US 7,943,310 B2
• Filed: 08/30/2007
• Issued: 05/17/2011
• Est. Priority Date: 08/30/2006
• Status: Active Grant

• Current Assignee: Centocor Ortho Biotech Incorporated (Johnson & Johnson)
• Original Assignee: Centocor Ortho Biotech Incorporated (Johnson & Johnson)
• Inventors: Song, Xiao-yu, Li, Xilin
• Primary Examiner(s): MYERS, CARLA J
• Application Number:
  US11/847,812
• Publication Number:
  US 20090054253A1
• Time in Patent Office: 1,356 Days
• Field of Search: None
• US Class Current: 435/6.11
• 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 2600/136 Screening for pharmacological compounds
• CPC Class Codes: C12Q 2600/158 Expression markers

Abstract

A method for prognostic or diagnostic assessment of a gastrointestinal-related disorder, such as ulcerative colitis, in a subject correlates the presence, absence, and/or magnitude of a gene in a sample with a reference standard to determine the presence and/or severity of the disorder, and/or the response to treatment for the disorder. The method enables identification of the effectiveness of candidate therapies.

Claims

1. A method for determining the likelihood that a human subject with ulcerative colitis will respond to an anti-TNFα

therapy, comprising;

a) preparing a sample of mRNA from a specimen obtained from a colon biopsy of a human subject with ulcerative colitis treated with the anti-TNFα

therapy;

b) contacting the sample with a panel of nucleic acid probes that hybridize to the nucleic acid sequences of SEQ ID NOS;

8, 9, 28, 37, and 66;

c) hybridizing the sample with the panel of nucleic probes to detect levels of the mRNAs in the sample encoded by the nucleic acid sequences of SEQ ID NOS;

8, 9, 28, 37, and 66;

d) comparing the levels of the mRNAs in the sample encoded by the nucleic acid sequences of SEQ ID NOS;

8, 9, 28, 37, and 66 against a reference standard of mRNAs encoded by nucleic acid sequences of SEQ ID NOS;

8, 9, 28, 37, and 66; and

e) determining the likelihood that the human subject will respond to the anti-TNFα

therapy based on the comparison in step d).

2. The method of claim 1, wherein the anti-TNFα

therapy is an anti-TNFα

antibody.

3. The method of claim 2, wherein the anti-TNFα

antibody is infliximab.

4. The method of claim 1, wherein the determining step comprises performing a statistical comparison of the levels of the mRNAs in the sample from the subject to a reference standard to determine the likelihood that the subject will respond to the anti-TNFα

therapy.

5. The method of claim 1, wherein the levels of the mRNAs in the sample are determined using RT-PCR.

6. The method of claim 1, wherein the specimen is obtained from the subject about 8 weeks after commencement of treatment with the anti-TNFα

therapy.

7. The method of claim 6, wherein the anti-TNFα

therapy is infliximab.

8. The method of claim 1, wherein the specimen is obtained from the subject about 30 weeks after commencement of treatment with the anti-TNFα

therapy.

9. The method of claim 8, wherein the anti-TNFα

therapy is infliximab.

10. The method of claim 1, wherein the determining step further comprises determining the likelihood that the subject will respond to the anti-TNFα

therapy if there is about a two fold change in the levels of mRNAs in the sample encoded by the nucleic acid sequences of SEQ ID NOS;

8, 9, 28, 37, and 66 as compared to the reference standard of mRNAs encoded by the nucleic acid sequences of SEQ ID NO;

8, 9, 28, 37 and 66.

11. The method of claim 1, further comprising the step of continuing treatment with the anti-TNFα

therapy if the subject is determined likely to respond to the therapy.

12. The method of claim 1, further comprising the step of discontinuing treatment with the anti-TNFα

therapy if the subject is determined not likely to respond to the therapy.