Methods for determining steroid responsiveness
First Claim
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1. A method for determining steroid responsiveness in a subject, the method comprising the steps of:
- (a) determining a first level of expression of RNA from a first gene known or suspected to be steroid responsive in a tissue, body fluid or cell from a subject undergoing steroid treatment;
(b) determining a second level of expression of RNA from a second gene known or suspected to be non-responsive to steroids in the tissue, body fluid or cell; and
(c) comparing the first and second levels of RNA to create a ratio;
(d) determining the steroid responsiveness of the subject based on the ratio, wherein the subject is steroid responsive if the ratio is higher than a predetermined control ratio for untreated or nonresponsive subjects, or similar to prior ratios for the subject when the subject was previously determined to be responsive.
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Abstract
The invention provides a diagnostics assay for measuring the responsiveness to a drug by comparing the mRNA levels of a gene that responds to the drug, such as a steroid, to the mRNA levels of a gene that does not respond to the drug. Methods according to the invention are useful for predicting the ability of a patient (or a tissue, body fluid or cell sample in vitro) to respond to a drug or steroid at any stage of their treatment (i.e., before, during or after), and to monitor the patient (or a tissue, body fluid or cell) over time to assess continued responsiveness to the drug or steroid.
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Citations
60 Claims
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1. A method for determining steroid responsiveness in a subject, the method comprising the steps of:
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(a) determining a first level of expression of RNA from a first gene known or suspected to be steroid responsive in a tissue, body fluid or cell from a subject undergoing steroid treatment;
(b) determining a second level of expression of RNA from a second gene known or suspected to be non-responsive to steroids in the tissue, body fluid or cell; and
(c) comparing the first and second levels of RNA to create a ratio;
(d) determining the steroid responsiveness of the subject based on the ratio, wherein the subject is steroid responsive if the ratio is higher than a predetermined control ratio for untreated or nonresponsive subjects, or similar to prior ratios for the subject when the subject was previously determined to be responsive. - View Dependent Claims (8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60)
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2. A method for determining steroid responsiveness in a tissue, body fluid or cell, the method comprising the steps of:
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(a) exposing a tissue, body fluid or cell sample in vitro to a steroid;
(b) determining a first level of expression of RNA from a first gene known or suspected to be steroid responsive;
(c) determining a second level of expression of RNA from a second gene known or suspected to be non-responsive to steroids;
end(d) comparing the first and second levels of RNA to create a ratio;
(e) determining the steroid responsiveness of the tissue, body fluid or cell based on the ratio, wherein the tissue, body fluid or cell sample is steroid responsive if the ratio is higher than a predetermined control ratio for untreated or nonresponsive subjects, or similar to prior ratios for the subject when the subject was previously determined to be responsive.
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3. A method for determining steroid responsiveness in a subject, the method comprising the steps of:
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(a) determining a level of expression of an RNA from a first gene known or suspected to be responsive to steroids in a pre-treatment tissue, body fluid, or cell from a subject;
(b) determining a level of expression of an RNA from a second gene known or suspected to be un-responsive to steroids in the pre-treatment tissue, body fluid, or cell;
(c) determining a post-treatment level of RNA expressed from the first gene;
(d) determining a post-treatment level of RNA expressed from the second gene;
(e) comparing the pre-treatment level of RNA expressed from the first gene to the pre-treatment level of RNA expressed from the second gene to create a first normalized value;
(f) comparing the post-treatment level of RNA expressed from the first gene to the post-treatment level of RNA expressed from the second gene to create a second normalized value;
(g) comparing the first normalized value to the second normalized value;
(h) determining steroid responsiveness of the subject based upon the comparison of the first normalized value to the second normalized value, wherein if the first normalized value is less than the second normalized value, it is indicative of steroid responsiveness in the tissue, body fluid or cell, and/or if the first normalized value is greater than or the same as the second normalized value, it is indicative of steroid non-responsiveness in the cell, and/or wherein the difference between the first normalized value and the second normalized value correlates to the ability of the subject to respond to the steroid.
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4. A method for determining an effective dose of a steroid in a subject, the method comprising the steps of:
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(a) administering to a subject a dose of a steroid;
(b) determining a first level of expression of RNA from a first gene known or suspected to be steroid responsive in a tissue, body fluid, or cell from the subject;
(c) determining a second level of expression of RNA from a second gene known or suspected to be non-responsive to steroids in the tissue, body fluid, or cell; and
(d) comparing the first and second levels of RNA to create a ratio;
(e) determining the effective dose of the steroid in the subject based on the ratio, wherein the difference between the first RNA level and the second RNA level is indicative of the effectiveness of the steroid dose in the subject.
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5. A method for monitoring a subject'"'"'s ability to respond to a steroid, the method comprising the steps of:
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(a) administering to a subject a dose of steroid;
(b) determining a first level of expression of RNA from a first gene known or suspected to be steroid responsive in a tissue, body fluid, or cell from the subject;
(c) determining a second level of expression of RNA from a second gene known or suspected to be non-responsive to steroids in the tissue, body fluid, or cell; and
(d) comparing the first and second levels of RNA to create a ratio;
(e) monitoring the subject'"'"'s ability to respond to the steroid based upon the ratio, wherein the subject is steroid responsive if the ratio is higher than a predetermined control ratio for untreated or nonresponsive subjects, or similar to prior ratios for the subject when the subject was previously determined to be responsive.
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6. A method for determining drug responsiveness in a subject undergoing drug treatment, the method comprising the steps of:
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(a) determining a first level of expression of RNA from a first gene known or suspected to be drug-responsive in a tissue, body fluid, or cell from a subject undergoing treatment with a drug;
(b) determining a second level of expression of RNA from a second gene known or suspected to be non-responsive to the drug in the tissue, body fluid, or cell; and
(c) comparing the first and second levels of RNA to create a ratio;
(d) determining drug responsiveness in the subject undergoing drug treatment based upon the ratio, wherein the subject is drug-responsive if the first level is higher than the second level and the subject is non-responsive to drug if the second level is higher than the first level.
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7. A method for determining drug responsiveness in a tissue, body fluid or cell, the method comprising the steps of:
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(a) exposing a tissue, body fluid or cell in vitro to a drug;
(b) determining a first level of expression of RNA from a first gene known or suspected to be drug-responsive;
(c) determining a second level of expression of RNA from a second gene known or suspected to be non-responsive to the drug; and
(d) comparing the first and second levels of RNA to create a ratio;
(e) determining drug responsiveness in the tissue, body fluid, or cell based upon the ratio, wherein the tissue, body fluid or cell is drug-responsive if the first level is higher than the second level and the tissue, body fluid or cell is non-responsive to the drug if the second level is higher than the first level.
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Specification