TREATMENT OF A DISEASE OF THE GASTROINTESTINAL TRACT WITH AN IMMUNOMODULATOR

1 .- 323 . (canceled)

324 . A method of treating a gastrointestinal (GI) inflammatory disease or condition in a subject in need thereof, comprising:

topically administering to the subject a pharmaceutical formulation comprising a therapeutically effective amount of a glycoprotein, said topical administration comprising:

orally administering an ingestible device to the subject, said device containing the pharmaceutical formulation; and

releasing the pharmaceutical formulation from the device (a) to a section or subsection of the subject's GI tract containing one or more inflammatory disease sites; or (b) proximal to a section or subsection of the subject's GI tract containing one or more inflammatory disease sites;

thereby treating at least one of the one or more disease sites.

325 . The method of claim 324 , wherein the device comprises a self-localization mechanism configured to determine a device location within the subject's GI tract, and the method further comprises determining the device location within the subject's GI tract via the device self-localization mechanism.

326 . The method of claim 325 , wherein determining the device location within the subject's GI tract via the device self-localization mechanism comprises detecting one or more device transitions between portions of the subject's GI tract; optionally, the one or more device transitions occurs between portions of the GI tract selected from the group consisting of: mouth and stomach; esophagus and stomach; stomach and duodenum; duodenum and jejunum; jejunum and ileum; ileum and cecum; and cecum and ascending colon; and combinations of any two or more of the foregoing.

327 . The method of claim 326 , wherein the device self-localizes to the stomach, duodenum, jejunum, ileum, cecum, ascending colon, or traverse colon with at least 80% accuracy; optionally, with at least 85% accuracy.

328 . The method of claim 324 , wherein the release of the formulation from the device is autonomously triggered based on the self-localization of the device to a pre-selected location within the subject's GI tract; optionally, the pre-selected location is selected from the group consisting of the stomach, the duodenum, the jejunum, the ileum, the cecum, the ascending colon, and the traverse colon.

329 . The method of claim 328 , wherein the release of the formulation from the device occurs at substantially the same time as the device self-localizes to the pre-selected location.

330 . The method of claim 324 , wherein the method provides a ratio of glycoprotein concentration in the subject's GI tissue to glycoprotein concentration in the subject's blood, serum, or plasma ranging from about 2:1 to about 3000:1, about 2:1 to about 2000:1, about 2:1 to about 1000:1, or about 2:1 to about 600:1.

331 . The method of claim 324 , wherein the therapeutically effective amount of the glycoprotein is an induction dose.

332 . The method of claim 324 , wherein the therapeutically effective amount of the glycoprotein is a maintenance dose.

333 . The method of claim 324 , wherein the glycoprotein is a peptide.

334 . The method of claim 324 , wherein the glycoprotein is a granulocyte-macrophage colony-stimulating factor (GM-CSF), optionally selected from sargramostim and molgramostim or a biosimilar thereof.

335 . The method of claim 324 , wherein the glycoprotein is a small molecule, and the pharmaceutical formulation containing the glycoprotein optionally comprises one or more pharmaceutically acceptable excipients.

336 . A method of treating an inflammatory bowel disease (IBD) in a subject in need thereof, the method comprising:

topically administering a pharmaceutical formulation comprising a therapeutically effective amount of a granulocyte-macrophage colony-stimulating factor (GM-CSF), (a) to a section or subsection of the gastrointestinal (GI) tract of the subject; or (b) proximal to a section or subsection of the GI tract of the subject; wherein said section or subsection contains one or more inflammatory disease sites;

thereby treating at least one of the one or more inflammatory disease sites.

337 . The method of claim 336 , wherein the pharmaceutical formulation is contained in an ingestible device, said device comprising a self-localization mechanism configured to determine a device location within the subject's GI tract, and the method further comprises determining the device location within the subject's GI tract via the device self-localization mechanism.

338 . The method of claim 336 , wherein the topical administration comprises:

orally administering the ingestible device to the subject; and

releasing the pharmaceutical formulation from the device (a) to a section or subsection of the subject's GI tract containing one or more inflammatory disease sites; or (b) proximal to a section or subsection of the subject's GI tract containing one or more inflammatory disease sites.

339 . The method of claim 337 , wherein determining the device location within the subject's GI tract via the device self-localization mechanism comprises detecting one or more device transitions between portions of the subject's GI tract; optionally, the one or more device transitions occurs between portions of the GI tract selected from the group consisting of: mouth and stomach; esophagus and stomach; stomach and duodenum; duodenum and jejunum; jejunum and ileum; ileum and cecum; and cecum and ascending colon; and combinations of any two or more of the foregoing.

340 . The method of claim 336 , wherein the method provides a ratio of the granulocyte-macrophage colony-stimulating factor, or the biosimilar thereof, concentration in the subject's GI tissue to granulocyte-macrophage colony-stimulating factor, concentration in the subject's blood, serum, or plasma ranging from about 2:1 to about 3000:1, about 2:1 to about 2000:1, about 2:1 to about 1000:1, or about 2:1 to about 600:1.

341 . An ingestible device comprising:

a pharmaceutical formulation comprising a therapeutically effective amount of a glycoprotein;

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 (a) determine a location of the ingestible device in the GI tract of the subject; and (b) release the formulation from the device at a pre-selected location of the GI tract;

wherein the ingestible device is a self-localizing ingestible device configured for use in treating an inflammatory gastrointestinal disease or condition in a subject.

342 . The ingestible device of claim 341 , wherein the device self-localizes in the pre-selected location of the GI tract of the subject with an accuracy of at least 80%; optionally, the pre-selected location is selected from the group consisting of stomach, duodenum, jejunum, ileum, cecum, ascending colon, and traverse colon.

343 . The ingestible device of claim 342 , further comprising:

a housing;

a force generator located within the housing; and

a storage reservoir located within the housing, wherein the storage reservoir stores the pharmaceutical formulation;

wherein the ingestible device is configured such that the force generator generates a force, thereby initiating the release of the formulation from the ingestible device into the pre-selected location of the GI tract.