Treatment of a disease of the gastrointestinal tract with a chst15 inhibitor
AssigneeProgenity, Inc.
InventorsMitchell Lawrence Jones, Sharat Singh, Christopher Loren Wahl, Harry Stylli
Life of this patent
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Abstract
This disclosure features methods and compositions for treating diseases of the gastrointestinal tract with a CHST15 inhibitor, to be administered via an ingestible device.
Claims383
A method of treating a disease of the gastrointestinal tract in a subject, comprising:
- administering to the subject a pharmaceutical formulation that comprises an CHST15 inhibitor,
- wherein the pharmaceutical formulation is released at a location in the gastrointestinal tract of the subject that is proximate to one or more sites of disease.
A method of treating a disease of the gastrointestinal tract in a subject, comprising:
- administering to the subject an ingestible device comprising a housing, a reservoir containing a pharmaceutical formulation, and a release mechanism for releasing the pharmaceutical formulation from the device;
- wherein the reservoir is releasably or permanently attached to the exterior of the housing or internal to the housing;
- wherein the pharmaceutical formulation comprises an CHST15 inhibitor, and
- the ingestible device releases the pharmaceutical formulation at a location in the gastrointestinal tract of the subject that is proximate to one or more sites of disease.
A method of treating a disease of the gastrointestinal tract in a subject, comprising:
- administering to the subject an ingestible device comprising a housing, a reservoir containing a pharmaceutical formulation, and a release mechanism for releasing the pharmaceutical formulation from the device;
- wherein the reservoir is internal to the device;
- wherein the pharmaceutical formulation comprises an CHST15 inhibitor, and
- the ingestible device releases the pharmaceutical formulation at a location in the gastrointestinal tract of the subject that is proximate to one or more sites of disease.
The method of any one of the preceding claims, wherein the formulation comprises a human equivalent dose (HED) of the CHST15 inhibitor.
A method of treating a disease of the gastrointestinal tract in a subject, comprising:
- releasing a CHST15 inhibitor at a location in the gastrointestinal tract of the subject that is proximate to one or more sites of disease, wherein the method comprises administering to the subject a pharmaceutical composition comprising a therapeutically effective amount of the CHST15 inhibitor.
The method of any one of the preceding claims, wherein the method provides a concentration of the CHST15 inhibitor in the plasma of the subject that is less than 3 μg/ml.
The method of any one of the preceding claims, wherein the location at which the CHST15 inhibitor is released is 10 cm or less from one or more sites of disease.
The method of any one of the preceding claims, wherein the location at which the CHST15 inhibitor is released is 5 cm or less from one or more sites of disease.
The method of any one of the preceding claims, wherein the location at which the CHST15 inhibitor is released is 2 cm or less from one or more sites of disease.
The method of any one of the preceding claims, wherein the CHST15 inhibitor is released by mucosal contact.
The method of any one of the preceding claims, wherein the CHST15 inhibitor is delivered to the location by a process that does not comprise systemic transport of the CHST15 inhibitor.
The method of any one of the preceding claims, further comprising identifying the one or more sites of disease by a method comprising imaging of the gastrointestinal tract.
The method of claim any one of the preceding claims, wherein the method comprises identifying the disease site prior to administering the pharmaceutical composition.
The method of any one of the preceding claims, comprising (a) identifying a subject having a disease of the gastrointestinal tract and (b) evaluating the subject for suitability to treatment.
The method of any one of the preceding claims, wherein the amount of the CHST15 inhibitor that is administered is from about 1 mg to about 500 mg.
The method of any one of the preceding claims, wherein the CHST15 inhibitor is an inhibitory nucleic acid whose nucleotide sequence is complementary to all or part of any one of SEQ ID NOs:
- 1-4).
The method of any one of the preceding claims, wherein the CHST15 inhibitor is an inhibitory nucleic acid whose nucleotide sequence is complementary to all of any one of SEQ ID NOs:
- 1-4).
The method of any one of the preceding claims, comprising administering (i) an amount of the CHST15 inhibitor that is an induction dose.
The method of any one of the preceding claims, wherein the method comprises releasing the CHST15 inhibitor at the location in the gastrointestinal tract as a single bolus.
A method of treating a disease of the large intestine of a subject, comprising:
- releasing a CHST15 inhibitor at a location in the proximal portion of the large intestine of the subject that is proximate to one or more sites of disease,
- wherein the method comprises administering endoscopically to the subject a therapeutically effective amount of the CHST15 inhibitor, wherein the method does not comprise releasing more than 20% of the CHST15 inhibitor at a location that is not proximate to a site of disease.
A method of treating a disease of the gastrointestinal tract in a subject, comprising:
- releasing a CHST15 inhibitor at a location in the proximal portion of the large intestine of the subject that is proximate to one or more sites of disease, wherein the method comprises administering endoscopically to the subject a pharmaceutical composition comprising a therapeutically effective amount of the CHST15 inhibitor, wherein the pharmaceutical composition is an ingestible device.
The method of any one of the preceding claims, further comprising administering a second agent orally, intravenously or subcutaneously, wherein the second agent is the same CHST15 inhibitor;
- a different CHST15 inhibitor;
- or an agent having a different biological target from the CHST15 inhibitor, wherein the second agent is an agent suitable for treating an inflammatory bowel disease.
The method of any one of the preceding claims, wherein the method comprising monitoring the progress of the disease.
A method of treating a disease of the gastrointestinal tract in a subject, comprising:
- releasing a CHST15 inhibitor at a location in the gastrointestinal tract of the subject that is proximate to one or more sites of disease, wherein the method comprises administering to the subject a pharmaceutical composition comprising a therapeutically effective amount of the CHST15 inhibitor the method comprising one or more of the following steps:
- a) identifying a subject having a disease of the gastrointestinal tract;
- b) determination of the severity of the disease;
- c) determination of the location of the disease;
- d) evaluating the subject for suitability to treatment;
- e) administration of an induction dose of the CHST15 inhibitor;
- f) monitoring the progress of the disease;
- and/or
- g) optionally repeating steps e) and f) one or more times.
A CHST15 inhibitor delivery apparatus comprising:
- an ingestible housing comprising a reservoir having a pharmaceutical composition comprising a therapeutically effective amount of the CHST15 inhibitor stored therein;
- a detector coupled to the ingestible housing, the detector configured to detect when the ingestible housing is proximate to a respective disease site of the one of the one or more sites of disease;
- a valve system in fluid communication with the reservoir system;
- and
- a controller communicably coupled to the valve system and the detector, the controller configured to cause the valve system to open in response to the detector detecting that the ingestible housing is proximate to the respective disease site so as to release the therapeutically effective amount of the CHST15 inhibitor at the respective disease site.
A composition comprising a therapeutically effective amount of the CHST15 inhibitor of any one of the preceding claims, wherein the composition is capable of releasing the CHST15 inhibitor at a location in the gastrointestinal tract of the subject.
A CHST15 inhibitor for use in a method of treating a disease of the gastrointestinal tract in a subject, wherein the method comprises orally administering to the subject an ingestible device loaded with the CHST15 inhibitor, wherein the CHST15 inhibitor is released by the device at a location in the gastrointestinal tract of the subject that is proximate to one or more sites of disease.
An attachable reservoir containing a CHST15 inhibitor for use in a method of treating a disease of the gastrointestinal tract, wherein the method comprises attaching the reservoir to a device housing to form an ingestible device and orally administering the ingestible device to a subject, wherein the CHST15 inhibitor is released by device at a location in the gastrointestinal tract of the subject that is proximate to one or more sites of disease.
A composition comprising or consisting of an ingestible device loaded with a therapeutically effective amount of a CHST15 inhibitor, for use in a method of treatment, wherein the method comprises orally administering the composition to the subject, wherein the CHST15 inhibitor is released by the device at a location in the gastrointestinal tract of the subject that is proximate to one or more sites of disease.
An ingestible device loaded with a therapeutically effective amount of a CHST15 inhibitor, wherein the device is controllable to release the CHST15 inhibitor at a location in the gastrointestinal tract of the subject that is proximate to one or more sites of disease.
A method for treating colitis in a subject, wherein the colitis is associated with treatment of the subject with one or more immuno-oncology agents, the method comprising releasing an CHST15 inhibitor at a location in the gastrointestinal tract of the subject that is proximate to one or more sites of disease, wherein the method comprises administering to the subject a pharmaceutical composition comprising a therapeutically effective amount of the CHST15 inhibitor.
A method for treating colitis in a subject comprising:
- determining that the subject has colitis associated with treatment of the subject with one or more immuno-oncology agents;
- and
- releasing an CHST15 inhibitor at a location in the gastrointestinal tract of the subject that is proximate to one or more sites of colitis, wherein the method comprises administering to the subject a pharmaceutical composition comprising a therapeutically effective amount of the CHST15 inhibitor. In some embodiments, the pharmaceutical composition is an ingestible device. In some embodiments, the pharmaceutical composition is an ingestible device and the method comprises administering orally to the subject the pharmaceutical composition.
A method for treating colitis, comprising releasing a CHST15 inhibitor at a location in the gastrointestinal tract of a subject who has been determined to have colitis associated with treatment of the subject with one or more immuno-oncology agents, wherein the location is proximate to one or more sites of colitis, wherein the method comprises administering to the subject a pharmaceutical composition comprising a therapeutically effective amount of the CHST15 inhibitor.
An ingestible device, comprising:
- an CHST15 inhibitor;
- one or more processing devices;
- and
- one more machine readable hardware storage devices storing instructions that are executable by the one or more processing devices to determine a location of the ingestible device in a portion of a GI tract of a subject to an accuracy of at least 85%.
An ingestible device, comprising:
- an CHST15 inhibitor;
- one or more processing devices;
- and
- one more machine readable hardware storage devices storing instructions that are executable by the one or more processing devices to determine that the ingestible device is in the cecum of a subject to an accuracy of at least 70%.
An ingestible device, comprising:
- an CHST15 inhibitor;
- one or more processing devices;
- and
- one more machine readable hardware storage devices storing instructions that are executable by the one or more processing devices to transmit data to a device capable of implementing the data to determine a location of the medical device in a portion of a GI tract of a subject to an accuracy of at least 85%.
An ingestible device, comprising:
- an CHST15 inhibitor;
- one or more processing devices;
- and
- one more machine readable hardware storage devices storing instructions that are executable by the one or more processing devices to transmit data to an external device capable of implementing the data to determine that the ingestible device is in the cecum of subject to an accuracy of at least 70%.
An ingestible device, comprising:
- a housing;
- a gas generating cell located within the housing;
- and
- a storage reservoir located within the housing,
- wherein:
- the storage reservoir stores a CHST15 inhibitor;
- and
- the ingestible device is configured so that, when the gas generating cell generates a gas, the CHST15 inhibitor exits the ingestible device via an opening in the ingestible device.
A reservoir configured for use in an ingestible device, wherein the reservoir comprises a therapeutic agent.
A kit, comprising:
- an ingestible device;
- and
- a reservoir configured for use in an ingestible device, wherein the reservoir comprises a therapeutic agent.
Dependencies are inferred from the claim text.