Methods, systems, and kits for treatment of inflammatory diseases targeting tl1a
AssigneePrometheus Biosciences, Inc.
InventorsFadi Towfic, Yong Wang, Olivier Laurent, Jiandong Lu, Allison Luo
Life of this patent
Estimating the term…
Abstract
Provided are methods, systems, and kits for selecting a subject for treatment with an inhibitor of Tumor necrosis factor-like cytokine 1A (TL1A) activity or expression based on a presence of one or more genotypes associated with a positive therapeutic response to the inhibitor of TL1A. Also provided are methods, systems and kits for detecting the one or more genotypes described herein.
Claims144
A method of treating an inflammatory, a fibrotic, or a fibrostenotic disease or condition in a subject, the method comprising:
- administering to the subject a therapeutically effective amount of an inhibitor of Tumor necrosis factor-like cytokine 1A (TL1A) activity or expression, wherein the subject is selected based on a Predictive Response Index (PRI) above a cutoff, wherein the PRI is calculated from a combination of polymorphisms determined from a sample from the subject and the PRI above the cutoff predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of at least about 29%.
A method of treating an inflammatory, a fibrotic, or a fibrostenotic disease or condition in a subject, the method comprising:
- (a) determining whether the subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition is suitable for treatment with an inhibitor of TL1A activity or expression by:
- (i) obtaining or having obtained a sample from the subject;
- (ii) subjecting the sample to an assay adapted to detect a combination of polymorphisms;
- (iii) calculating a Predictive Response Index (PRI) from the combination of polymorphisms, wherein the subject is determined to be suitable for treatment with an inhibitor of TL1A activity or expression if the PRI is above a cutoff;
- and
- (b) treating the subject by administering a therapeutically effective amount of the inhibitor of TL1A activity or expression to the subject.
A method of determining a Predictive Response Index (PRI) for a subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition, the method comprising:
- (a) obtaining or having obtained a sample from the subject;
- (b) subjecting the sample to an assay adapted to detect a combination of polymorphisms;
- and
- (c) calculating the PRI from the combination of polymorphisms, wherein the PRI above a cutoff indicates the subject is suitable for treatment with an inhibitor of TL1A activity or expression.
A method of selecting a subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition for treatment with an inhibitor of TL1A activity or expression, the method comprising:
- (a) obtaining or having obtained a sample from the subject;
- (b) subjecting the sample to an assay adapted to detect a combination of polymorphisms;
- (c) calculating a Predictive Response Index (PRI) from the combination of polymorphisms;
- and
- (d) selecting the subject for treatment with the inhibitor of TL1A activity or expression if the PRI is above a cutoff.
A computer-implemented method of determining a Response Probability Score (RPS) for a subject, the method comprising:
- (a) receiving genotype data obtained from a sample from the subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition, wherein the genotype data comprises a combination of polymorphisms;
- (b) analyzing the genotype data with a first statistical algorithm configured to produce a Model Risk Score (MRS) for the subject by performing operations comprising:
- (i) assigning a weighted numerical value to each polymorphism in the combination of polymorphisms to produce a plurality of weighted values;
- and
- (ii) summing the plurality of weighted values;
- (c) providing the MRS to a second statistical algorithm configured to perform a logarithmic function on the MRS to produce a Response Probability Score (RPS);
- and
- (d) applying a cutoff to the RPS, wherein the RPS relative to the cutoff is indicative that the subject is suitable for treatment with an inhibitor of TL1A activity or expression for treatment of the inflammatory, fibrotic, or fibrostenotic disease or condition.
A computer-implemented method of determining a Response Probability Score (RPS) for a subject, the method comprising:
- (a) obtaining a plurality of multi-single nucleotide polymorphism (multi-SNP) models, wherein each multi-SNP model is predictive of a positive therapeutic response to an inhibitor of TL1A activity or expression for treatment of an inflammatory, a fibrotic, or a fibrostenotic disease or condition in the subject;
- (b) receiving genotype data for a plurality of polymorphisms obtained from a sample from the subject;
- (c) calculating a Model Risk Score (MRS) utilizing one or more statistical algorithms configured to perform operations comprising:
- (i) assigning a weighted numerical value to each polymorphism of the plurality of polymorphisms to produce a plurality of weighted values, and (ii) summing the plurality of weighted values;
- and
- (d) applying a logarithmic scale and a cutoff to the MRS to produce a Response Probability Score (RPS).
A method of treating an inflammatory, a fibrotic, or a fibrostenotic disease or condition in a subject, the method comprising:
- administering to the subject a therapeutically effective amount of an inhibitor of Tumor necrosis factor-like cytokine 1A (TL1A) activity or expression, wherein the subject is selected based on a comparison of a Predictive Response Index (PRI) to a cutoff according to (1) or (2):
- (1) if the PRI has a positive correlation with a Response Probability Score (RPS), then the subject is selected if the PRI is above the cutoff;
- or
- (2) if the PRI has a negative correlation with a RPS, then the subject is selected if the PRI is below the cutoff,
- and wherein the PRI is calculated from a combination of polymorphisms determined from a sample from the subject and the comparison of the Predictive Response Index (PRI) to the cutoff according to (1) or (2) predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression with a positive predictive value of at least about 29%.
A method of treating an inflammatory, a fibrotic, or a fibrostenotic disease or condition in a subject, the method comprising:
- (a) determining whether the subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition is suitable for treatment with an inhibitor of TL1A activity or expression by:
- (i) obtaining or having obtained a sample from the subject;
- (ii) subjecting the sample to an assay adapted to detect a combination of polymorphisms;
- (iii) calculating a Predictive Response Index (PRI) from the combination of polymorphisms, wherein the subject is determined to be suitable for treatment with an inhibitor of TL1A activity or expression based on a comparison of the PRI to a cutoff according to (1) or (2):
- (1) if the PRI has a positive correlation with RPS, then the subject is determined to be suitable if the PRI is above the cutoff;
- or
- (2) if the PRI has a negative correlation with RPS, then the subject is determined to be suitable if the PRI is below the cutoff, and
- (b) treating the subject by administering a therapeutically effective amount of the inhibitor of TL1A activity or expression to the subject.
A method of determining a comparison of a Predictive Response Index (PRI) to a cutoff for a subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition, the method comprising:
- (a) obtaining or having obtained a sample from the subject;
- (b) subjecting the sample to an assay adapted to detect a combination of polymorphisms;
- and
- (c) calculating the PRI from the combination of polymorphisms, wherein the comparison is determined according to (1) or (2):
- (1) if the PRI has a positive correlation with RPS, then the subject is determined to be suitable for treatment with an inhibitor of TL1A activity or expression if the PRI is above the cutoff;
- or
- (2) if the PRI has a negative correlation with RPS, then the subject is determined to be suitable for treatment with an inhibitor of TL1A activity or expression if the PRI is below the cutoff.
A method of selecting a subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition for treatment with an inhibitor of TL1A activity or expression, the method comprising:
- (a) obtaining or having obtained a sample from the subject;
- (b) subjecting the sample to an assay adapted to detect a combination of polymorphisms;
- (c) calculating a Predictive Response Index (PRI) from the combination of polymorphisms;
- and
- (d) selecting the subject for treatment with the inhibitor of TL1A activity or expression based on a comparison of the PRI to a cutoff according to (1) or (2):
- (1) if the PRI has a positive correlation with RPS, then selecting the subject if the PRI is above the cutoff;
- or
- (2) if the PRI has a negative correlation with RPS, then selecting the subject if the PRI is below the cutoff.
A method of treating an inflammatory, a fibrotic, or a fibrostenotic disease or condition in a subject, the method comprising:
- administering to the subject a therapeutically effective amount of an inhibitor of TL1A activity or expression, based, at least partially, on a Predictive Response Index (PRI) calculated by applying one or more statistical algorithms to a combination of polymorphisms detected from a sample obtained from the subject and determining a comparison of the PRI to a cutoff to predicts a positive therapeutic response in the subject to a treatment with the inhibitor of TL1A activity or expression.
A method of treating an inflammatory, a fibrotic, or a fibrostenotic disease or condition in a subject, the method comprising:
- administering an inhibitor of TL1A activity or expression to the subject that is predicted to exhibit a positive therapeutic response to the inhibitor of TL1A activity or expression, as determined by a Predictive Response Index (PRI) that is calculated by:
- (a) detecting a presence of a combination of polymorphisms in a sample from the subject;
- (b) applying a statistical algorithm to the combination of polymorphisms detected in step (a) to generate the PRI;
- and
- (c) determining a comparison of the PRI to a cutoff.
A method of treating an inflammatory, a fibrotic, or a fibrostenotic disease or condition in a subject, the method comprising:
- (a) determining whether the subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition is suitable for treatment with an inhibitor of TL1A activity or expression by:
- (i) obtaining or having obtained a sample from the subject;
- (ii) subjecting the sample to an assay adapted to detect a combination of polymorphisms;
- (iii) calculating a Predictive Response Index (PRI) from the combination of polymorphisms, wherein the PRI is further determined in a comparison to a cutoff;
- and
- (b) treating the subject by administering a therapeutically effective amount of the inhibitor of TL1A activity or expression to the subject.
A computer-implemented system comprising at least one processor and instructions executable by the at least one processor to provide an application configured to determine a Response Probability Score (RPS) for a subject by performing operations comprising:
- (a) receiving genotype data obtained from a sample from the subject with an inflammatory, a fibrotic, or a fibrostenotic disease or condition, wherein the genotype data comprises a combination of polymorphisms;
- (b) applying a first statistical algorithm to the genotype data, the first statistical algorithm configured to produce a Model Risk Score (MRS) for the subject by performing operations comprising:
- (i) assigning a weighted numerical value to each polymorphism in the combination of polymorphisms to produce a plurality of weighted values;
- and
- (ii) summing the plurality of weighted values;
- (c) applying a second statistical algorithm to the MRS, the second statistical algorithm configured to perform a logarithmic function on the MRS to produce a Response Probability Score (RPS);
- and
- (d) applying a cutoff to the RPS, wherein the RPS relative to the cutoff is indicative that the subject is suitable for treatment with an inhibitor of TL1A activity or expression for treatment of the inflammatory, fibrotic, or fibrostenotic disease or condition
A computer-implemented system comprising at least one processor and instructions executable by the at least one processor to provide an application configured to determine a Response Probability Score (RPS) for a subject by performing operations comprising:
- (a) receiving a plurality of multi-single nucleotide polymorphism (multi-SNP) models, wherein each multi-SNP model is predictive of a positive therapeutic response to an inhibitor of TL1A activity or expression for treatment of an inflammatory, a fibrotic, or a fibrostenotic disease or condition in the subject;
- (b) receiving genotype data for a plurality of polymorphisms obtained from a sample from the subject;
- (c) calculating a Model Risk Score (MRS) utilizing one or more statistical algorithms configured to perform operations comprising:
- (i) assigning a weighted numerical value to each polymorphism of the plurality of polymorphisms to produce a plurality of weighted values, and (ii) summing the plurality of weighted values;
- and
- (d) applying a logarithmic scale and a cutoff to the MRS to produce a Response Probability Score (RPS).
Dependencies are inferred from the claim text.