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US 2009/0253133 A1Published application
Enhanced t cell receptor-mediated tumor necrosis factor superfamily and chemokine mrna expression in peripheral blood leukocytes in patients with crohn's disease
AssigneesHitachi Chemical Company, Ltd., Hitachi Chemical Research Center, Inc., Cedars-Sinai Medical Center
InventorsMasato Mitsuhashi, Stephan R. Targan
Life of this patent
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Abstract
A method is disclosed for determining whether a human having Crohn's disease is likely to respond to a therapy targeting a TNFSF member or a cytokine by measuring the level of certain mRNAs in response to a stimulus. A method of evaluating the effectiveness of a Crohn's disease therapy in a human is also disclosed. Furthermore, a method of screening compounds for use in the treatment of Crohn's disease is disclosed. A method of monitoring the disease state over time in Crohn's disease patients is also disclosed.
Claims30
A method of determining whether a human having Crohn's disease is likely to respond to a therapy, comprising:
- stimulating leukocytes in vitro in a first sample that comprises leukocytes from the human;
- after the stimulation, measuring the amount of an mRNA selected from the group consisting of tumor necrosis factor superfamily (“TNFSF”)-2, TNFSF-5, TNFSF-6, TNFSF-14, chemokine (C-C motif) ligand (“CCL”)-2, CCL-3, CCL-4, and chemokine (C-X-C motif) ligand (“CXCL”)-10 in the first sample;
- stimulating leukocytes in vitro in a second sample comprising leukocytes from the human with a control stimulus;
- measuring the amount of the mRNA in the second sample after stimulation;
- and
- determining a ratio of the amount of the mRNA in the first sample to the amount of the mRNA in the second sample, wherein the human is likely to respond to the therapy if the ratio is about 1.7:1 or greater.
3 more elements
A method of evaluating the effectiveness of a Crohn's disease therapy in a human, comprising:
- stimulating leukocytes in vitro in a first sample comprising leukocytes from the human;
- stimulating leukocytes in vitro in a second sample comprising leukocytes from the human with a control stimulus;
- measuring the amount of an mRNA selected from the group consisting of tumor necrosis factor superfamily (“TNFSF”)-2, TNFSF-5, TNFSF-6, TNFSF-14, chemokine (C-C motif) ligand (“CCL”)-2, CCL-3, CCL-4, and chemokine (C-X-C motif) ligand (“CXCL”)-10 in the first and second samples after stimulation;
- calculating a first ratio of the amount of the mRNA in the first sample to the amount of the mRNA in the second sample;
- administering the therapy to the human;
- stimulating leukocytes in vitro in a third sample comprising leukocytes from the human obtained after the administration of therapy;
- stimulating leukocytes in vitro in a fourth sample comprising leukocytes from the human obtained after the administration of therapy with the control stimulus;
- measuring the level of the mRNA in the third and fourth samples after stimulation;
- calculating a second ratio of the amount of the mRNA in the third sample to the amount of the mRNA in the fourth sample;
- and
- comparing the first and second ratios, wherein a significant difference in the ratios is indicative of an effective therapy.
8 more elements
A method of identifying a putative agent for treating Crohn's disease, comprising:
- obtaining first, second, third, and fourth samples comprising leukocytes from a human whose leukocytes demonstrate at least a 1.7-fold increase in the transcription of an mRNA selected from the group consisting of tumor necrosis factor superfamily (“TNFSF”)-2, TNFSF-5, TNFSF-6, TNFSF-14, chemokine (C-C motif) ligand (“CCL”)-2, CCL-3, CCL-4, and chemokine (C-X-C motif) ligand (“CXCL”)-10 when exposed to an anti-T cell receptor antibody;
- stimulating leukocytes in vitro in the first sample;
- stimulating leukocytes in vitro in the second sample with a control stimulus;
- measuring the amount of the mRNA in the first and second samples after stimulation;
- calculating a first ratio of the amount of the mRNA in the first sample to the amount of the mRNA in the second sample;
- exposing the third and fourth samples to the agent;
- stimulating leukocytes in vitro in the third sample after the exposure;
- stimulating leukocytes in vitro in the fourth sample with the control stimulus after the exposure;
- measuring the level of the mRNA in the third and fourth samples after stimulation;
- calculating a second ratio of the amount of the mRNA in the third sample to the amount of the mRNA in the fourth sample;
- and
- comparing the first and second ratios, wherein a significant difference in the ratios is indicative of a putative agent.
9 more elements
A method of evaluating the state of Crohn's disease in a human, comprising:
- stimulating leukocytes in vitro in a first sample that comprises leukocytes and is obtained at a first time from the human;
- after the stimulation, measuring the amount of an mRNA selected from the group consisting of tumor necrosis factor superfamily (“TNFSF”)-2, TNFSF-5, TNFSF-6, TNFSF-14, chemokine (C-C motif) ligand (“CCL”)-2, CCL-3, CCL-4, and chemokine (C-X-C motif) ligand (“CXCL”)-10 in the first sample;
- stimulating leukocytes in vitro with a control stimulus in a second sample comprising leukocytes obtained from the human at the first time;
- measuring the amount of the mRNA in the second sample after stimulation;
- determining a first ratio of the amount of the mRNA in the first sample to the amount of the mRNA in the second sample;
- stimulating leukocytes in vitro in a third sample that comprises leukocytes and is obtained from the human at a second time that is subsequent to the first time;
- after the stimulation, measuring the amount of the mRNA in the third sample;
- stimulating leukocytes in vitro with a control stimulus in a fourth sample comprising leukocytes obtained from the human at the second time;
- measuring the amount of the mRNA in the fourth sample after stimulation;
- determining a second ratio of the amount of the mRNA in the third sample to the amount of the mRNA in the fourth sample;
- and
- comparing the first and second ratios, wherein a significant difference in the first and second ratios is indicative of a change in the disease state.
9 more elements
Dependencies are inferred from the claim text.