Type I interferon signatures and methods of use
AssigneeJanssen Biotech, Inc.
InventorsMatteo Cesaroni, Marc Chevrier, Jarrat Jordan, Jessica Schreiter
Life of this patent
Estimating the term…
Abstract
Type I interferon (IFN-I) signatures are useful in methods of diagnosing whether a subject (or patient) with IFN-I mediated disease will be responsive to treatment with an IFN-I inhibitor and treating or refraining from treating the subjects.
Claims20
A method of treating a subject having a type I interferon (IFN-I) mediated disease that is responsive to treatment with an IFN-I inhibitor, comprising:
- a) providing a biological sample from the subject;
- b) assaying gene expression of genes DHX58, EIF2AK2, HERC5, IFI44, IFI44L, IFI6, IRF7, PARP9, PLSCR1 and SAMD9L in the biological sample;
- c) determining a combined expression value of the genes DHX58, EIF2AK2, HERC5, IFI44, IFI44L, IFI6, IRF7, PARP9, PLSCR1 and SAMD9L in the biological sample;
- and
- d) treating the subject with the IFN-I inhibitor when the combined expression value is equal to or higher than a threshold value, wherein the combined expression value is a sum of (i) normalized threshold cycle (CT) values (SUMΔCT) of genes DHX58, EIF2AK2, HERC5, IFI44, IFI44L, IFI6, IRF7, PARP9, PLSCR1 and SAMD9 and the threshold value is SUMΔCT of 57.474 or (ii) log 2 fold changes of normalized differential expression between the biological sample and a biological sample obtained from one or more healthy controls (SUMlog2(2{circumflex over ( )}−ddCT)) of genes DHX58, EIF2AK2, HERC5, IFI44, IFI44L, IFI6, IRF7, PARP9, PLSCR1 and SAMD9L and the threshold value is SUMlog2(2{circumflex over ( )}−ddCT) of 8.725.
A method of determining whether a subject having a type I interferon (IFN-I) mediated disease is responsive to treatment with an IFN-I inhibitor and deciding whether to treat the subject, comprising:
- a) providing a biological sample from the subject;
- b) assaying gene expression of genes DHX58, EIF2AK2, HERC5, IFI44, IFI44L, IF16, IRF7, PARP9, PLSCR1 and SAMD9L in the biological sample;
- c) determining a combined expression value of the genes DHX58, EIF2AK2, HERC5, IFI44, IFI44L, IF16, IRF7, PARP9, PLSCR1 and SAMD9L in the biological sample;
- d) diagnosing the subject with the IFN-I mediated disease as responsive to treatment with the IFN-I inhibitor when the combined expression value is equal to or higher than a threshold value or diagnosing the subject with the IFN-I mediated disease as non-responsive to treatment with the IFN-I inhibitor when the combined expression value is less than a threshold value;
- and
- e) administering the IFN-I inhibitor to the subject diagnosed as responsive to treatment with the IFN-I inhibitor or refraining from administering the IFN-I inhibitor to the subject diagnosed as non-responsive to treatment with the IFN-I inhibitor, wherein the combined expression value is a sum of (i) normalized threshold cycle (CT) values (SUMΔCT) of genes DHX58, EIF2AK2, HERC5, IFI44, IFI44L, IFI6, IRF7, PARP9, PLSCR1 and SAMD9L and the threshold value is SUMΔCT of 57.474, or (ii) log 2 fold changes of normalized differential expression between the biological sample and a biological sample obtained from one or more healthy controls (SUMlog2(2{circumflex over ( )}−ddCT)) of genes DHX58, EIF2AK2, HERC5, IFI44, IFI44L, IFI6, IRF7, PARP9, PLSCR1 and SAMD9L and the threshold value is SUMlog2(2{circumflex over ( )}−ddCT) of 8.725.
Dependencies are inferred from the claim text.