Methods of treating intestinal fibrosis using smad7 inhibition
AssigneeCelgene Corporation
InventorGiovanni MONTELEONE
Life of this patent
Estimating the term…
Abstract
The present invention relates to methods of treating, preventing or managing intestinal fibrosis by inhibiting SMAD7. The invention is also directed to methods of monitoring effectiveness of treatment or management of intestinal fibrosis using a SMAD7 antisense oligonucleotide, as well as methods of regulating SMAD7 antisense oligonucleotide treatment, based on analysis of Transforming Growth Factor-β (TGF-β) levels, α-Smooth Muscle Actin (a-SMA) levels, and/or phosphorylated Mothers Against Decapentaplegic Homolog 3 (p-SMAD3) levels.
Claims175
A method of treating, preventing or managing intestinal fibrosis or preventing collagen deposition, comprising inhibiting SMAD7 in a patient suffering from intestinal fibrosis or collagen deposition.
A method of treating, preventing or managing intestinal fibrosis or preventing collagen deposition, comprising inhibiting SMAD7 in an intestinal cell.
A method of treating, preventing or managing intestinal fibrosis in a patient, comprising administering to the patient an effective amount of a specific inhibitor of SMAD7.
A method for treating, preventing or managing intestinal fibrosis in a patient having intestinal fibrosis, wherein the method comprises (a) administering to the patient an initial dose of a SMAD7 antisense oligonucleotide;
- (b) analyzing the level of TGF-β (Transforming Growth Factor-β) in the patient;
- and (c) if the level of TGF-β is above normal levels of TGF-β, then administering to the patient a subsequent dose that is greater than or equal to the initial dose, or, if the level of TGF-β is below normal levels of TGF-β, then administering to the patient a subsequent dose that is equal to or smaller than the initial dose.
A method for treating, preventing or managing intestinal fibrosis in a patient having intestinal fibrosis, wherein the method comprises (a) analyzing the level of TGF-β in the patient;
- and (b) if the level of TGF-β is above normal levels of TGF-β, then administering to the patient an initial dose of a SMAD7 antisense oligonucleotide.
A method for treating, preventing or managing intestinal fibrosis in a patient having intestinal fibrosis, wherein the method comprises:
- (a) establishing a control level of TGF-β for the patient;
- (b) administering to the patient an initial dose of a SMAD7 antisense oligonucleotide;
- (c) analyzing the level of TGF-β in the patient;
- and (d) if the level of TGF-β is lower than the control level, then administering to the patient a subsequent dose that is the same as the initial dose or smaller than the initial dose, or, if the level of TGF-β is unchanged or increased compared to the control level, then administering to the patient a subsequent dose that is the same as the initial dose or greater than the initial dose or terminating the treatment.
A method for treating, preventing or managing intestinal fibrosis in a patient with intestinal fibrosis having above normal TGF-β levels following administration of a dose of a SMAD7 antisense oligonucleotide, said method comprising administering to said patient a further dose of said oligonucleotide that is greater than or equal to the prior dose.
A method for treating, preventing or managing intestinal fibrosis in a patient with intestinal fibrosis having below normal TGF-β levels following administration of a dose of SMAD7 antisense oligonucleotide, said method comprising administering to said patient a further dose of said oligonucleotide that is less than or equal to the prior dose.
A method of treating, preventing or managing intestinal fibrosis in a patient with intestinal fibrosis having above normal TGF-β levels, said method comprising administering to said patient a dose of a SMAD7 antisense oligonucleotide.
A method of monitoring the treatment or management of intestinal fibrosis in a patient with intestinal fibrosis, the method comprising analyzing TGF-β levels in the patient following each SMAD7 antisense oligonucleotide administration, wherein the absence of a decrease in TGF-β levels indicates that the treatment or management is not effective.
A method of treating, preventing or managing intestinal fibrosis in a patient with intestinal fibrosis having above normal levels of TGF-β, comprising increasing the amount of a SMAD7 antisense oligonucleotide administered to the patient until TGF-β levels in the patient decrease.
A SMAD7 antisense oligonucleotide for use in a method for treating, preventing or managing intestinal fibrosis in a patient having intestinal fibrosis, wherein the method comprises analyzing the level of TGF-β in the patient to determine appropriate levels of SMAD7 antisense oligonucleotide administration.
A SMAD7 antisense oligonucleotide for use in a method for treating, preventing or managing intestinal fibrosis in a patient having intestinal fibrosis, wherein the method comprises (a) analyzing the level of TGF-β in the patient;
- and (b) if the level of TGF-β is above normal levels of TGF-β, then administering to the patient an initial dose of the SMAD7 antisense oligonucleotide.
A method for treating, preventing or managing intestinal fibrosis in a patient having intestinal fibrosis, wherein the method comprises (a) administering to the patient an initial dose of a SMAD7 antisense oligonucleotide;
- (b) analyzing the level of p-SMAD3 in the patient;
- and (c) if the level of p-SMAD3 is above normal levels of p-SMAD3, then administering to the patient a subsequent dose that is greater than or equal to the initial dose, or, if the level of p-SMAD3 is below normal levels of p-SMAD3, then administering to the patient a subsequent dose that is equal to or smaller than the initial dose.
A method for treating, preventing or managing intestinal fibrosis in a patient having intestinal fibrosis, wherein the method comprises (a) analyzing the level of p-SMAD3 in the patient;
- and (b) if the level of p-SMAD3 is above normal levels of p-SMAD3, then administering to the patient an initial dose of a SMAD7 antisense oligonucleotide.
A method for treating, preventing or managing intestinal fibrosis in a patient having intestinal fibrosis, wherein the method comprises:
- (a) establishing a control level of p-SMAD3 for the patient;
- (b) administering to the patient an initial dose of a SMAD7 antisense oligonucleotide;
- (c) analyzing the level of p-SMAD3 in the patient;
- and (d) if the level of p-SMAD3 is lower than the control level, then administering to the patient a subsequent dose that is the same as the initial dose or smaller than the initial dose, or, if the level of p-SMAD3 is unchanged or increased compared to the control level, then administering to the patient a subsequent dose that is the same as the initial dose or greater than the initial dose or terminating the treatment.
A method for treating, preventing or managing intestinal fibrosis in a patient with intestinal fibrosis having above normal p-SMAD3 levels following administration of a dose of a SMAD7 antisense oligonucleotide, said method comprising administering to said patient a further dose of said oligonucleotide that is greater than or equal to the prior dose.
A method for treating, preventing or managing intestinal fibrosis in a patient with intestinal fibrosis having below normal p-SMAD3 levels following administration of a dose of SMAD7 antisense oligonucleotide, said method comprising administering to said patient a further dose of said oligonucleotide that is less than or equal to the prior dose.
A method of treating, preventing or managing intestinal fibrosis in a patient with intestinal fibrosis having above normal p-SMAD3 levels, said method comprising administering to said patient a dose of a SMAD7 antisense oligonucleotide.
A method of monitoring the treatment or management of intestinal fibrosis in a patient with intestinal fibrosis, the method comprising analyzing p-SMAD3 levels in the patient following each SMAD7 antisense oligonucleotide administration, wherein the absence of a decrease in p-SMAD3 levels indicates that the treatment or management is not effective.
A method of treating, preventing or managing intestinal fibrosis in a patient with intestinal fibrosis having above normal levels of p-SMAD3, comprising increasing the amount of a SMAD7 antisense oligonucleotide administered to the patient until p-SMAD3 levels in the patient decrease.
A SMAD7 antisense oligonucleotide for use in a method for treating, preventing or managing intestinal fibrosis in a patient having intestinal fibrosis, wherein the method comprises analyzing the level of p-SMAD3 in the patient to determine appropriate levels of SMAD7 antisense oligonucleotide administration.
A SMAD7 antisense oligonucleotide for use in a method for treating, preventing or managing intestinal fibrosis in a patient having intestinal fibrosis, wherein the method comprises (a) analyzing the level of p-SMAD3 in the patient;
- and (b) if the level of p-SMAD3 is above normal levels of p-SMAD3, then administering to the patient an initial dose of the SMAD7 antisense oligonucleotide.
A method for treating, preventing or managing intestinal fibrosis in a patient having intestinal fibrosis, wherein the method comprises (a) administering to the patient an initial dose of a SMAD7 antisense oligonucleotide;
- (b) analyzing the level of α-SMA in the patient;
- and (c) if the level of α-SMA is above normal levels of α-SMA, then administering to the patient a subsequent dose that is greater than or equal to the initial dose, or, if the level of α-SMA is below normal levels of α-SMA, then administering to the patient a subsequent dose that is equal to or smaller than the initial dose.
A method for treating, preventing or managing intestinal fibrosis in a patient having intestinal fibrosis, wherein the method comprises (a) analyzing the level of α-SMA in the patient;
- and (b) if the level of α-SMA is above normal levels of α-SMA, then administering to the patient an initial dose of a SMAD7 antisense oligonucleotide.
A method for treating, preventing or managing intestinal fibrosis in a patient having intestinal fibrosis, wherein the method comprises:
- (a) establishing a control level of α-SMA for the patient;
- (b) administering to the patient an initial dose of a SMAD7 antisense oligonucleotide;
- (c) analyzing the level of α-SMA in the patient;
- and (d) if the level of α-SMA is lower than the control level, then administering to the patient a subsequent dose that is the same as the initial dose or smaller than the initial dose, or, if the level of α-SMA is unchanged or increased compared to the control level, then administering to the patient a subsequent dose that is the same as the initial dose or greater than the initial dose or terminating the treatment.
A method for treating, preventing or managing intestinal fibrosis in a patient with intestinal fibrosis having above normal α-SMA levels following administration of a dose of a SMAD7 antisense oligonucleotide, said method comprising administering to said patient a further dose of said oligonucleotide that is greater than or equal to the prior dose.
A method for treating, preventing or managing intestinal fibrosis in a patient with intestinal fibrosis having below normal α-SMA levels following administration of a dose of SMAD7 antisense oligonucleotide, said method comprising administering to said patient a further dose of said oligonucleotide that is less than or equal to the prior dose.
A method of treating, preventing or managing intestinal fibrosis in a patient with intestinal fibrosis having above normal α-SMA levels, said method comprising administering to said patient a dose of a SMAD7 antisense oligonucleotide.
A method of monitoring the treatment or management of intestinal fibrosis in a patient with intestinal fibrosis, the method comprising analyzing α-SMA levels in the patient following each SMAD7 antisense oligonucleotide administration, wherein the absence of a decrease in α-SMA levels indicates that the treatment or management is not effective.
A method of treating, preventing or managing intestinal fibrosis in a patient with intestinal fibrosis having above normal levels of α-SMA, comprising increasing the amount of a SMAD7 antisense oligonucleotide administered to the patient until α-SMA levels in the patient decrease.
A SMAD7 antisense oligonucleotide for use in a method for treating, preventing or managing intestinal fibrosis in a patient having intestinal fibrosis, wherein the method comprises analyzing the level of α-SMA in the patient to determine appropriate levels of SMAD7 antisense oligonucleotide administration.
A SMAD7 antisense oligonucleotide for use in a method for treating, preventing or managing intestinal fibrosis in a patient having intestinal fibrosis, wherein the method comprises (a) analyzing the level of α-SMA in the patient;
- and (b) if the level of α-SMA is above normal levels of α-SMA, then administering to the patient an initial dose of the SMAD7 antisense oligonucleotide.
Dependencies are inferred from the claim text.