# US 10,869,840 B2 · Methods and articles for delivering viable cells into solid tissue > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,869,840 B2 - Document ID: US10869840B2 - Status: Granted - Kind: B2 - Application number: 15/455,075 - Filed: 2017-03-09 - Published: 2017-09-14 - Granted: 2020-12-22 - Earliest claimed: 2016-03-09 - Assignees: InCube Labs, LLC - Applicants: InCube Labs, LLC - Inventors: Mir Imran; Joel Harris - Web page: https://patentgrep.com/patent/US10869840B2 ## CPC - A61K 9/4816: {Wall or shell material} - A61B 5/14507: {specially adapted for measuring characteristics of body fluids other than blood (devices for taking samples of body liquids A61B10/0045)} - A61B 5/14539: {for measuring pH} - A61B 5/14546: {for measuring analytes not otherwise provided for, e.g. ions, cytochromes} - A61B 5/6861: {Capsules, e.g. for swallowing or implanting} - A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration} - A61K 9/06: Ointments; Bases therefor; {Other semi-solid forms, e.g. creams, sticks, gels (composition of ointments, creams or gels A61K47/00)} - A61K 9/4891: {Coated capsules; Multilayered drug free capsule shells (with drug coating for immediate release A61K9/4808; osmotic devices A61K9/0004)} - A61K 35/12: Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells (vaccines or medicinal preparations containing antigens or antibodies A61K39/00) - A61K 35/28: Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells - A61K 35/30: Nerves; Brain; Eyes; Corneal cells; Cerebrospinal fluid; Neuronal stem cells; Neuronal precursor cells; Glial cells; Oligodendrocytes; Schwann cells; Astroglia; Astrocytes; Choroid plexus; Spinal cord tissue - A61K 35/39: Pancreas; Islets of Langerhans (Langerhans cells of epidermis A61K35/36) - A61M 25/1002: {characterised by balloon shape (A61M25/1006, A61M25/1009 take precedence)} - A61M 31/002: {Devices for releasing a drug at a continuous and controlled rate for a prolonged period of time (artificial gland structures or devices A61F2/022; intra-uterine contraceptive devices A61F6/14; tampons for introducing into the vagina A61F13/20, A61L15/00; suppositories or bougies for intra-vaginal or intra-uterine application A61K9/02; physical forms of medicinal preparations for sustained or differential drug release A61K9/20, A61K9/50)} - A61P 3/10: for hyperglycaemia, e.g. antidiabetics - A61P 5/00: Drugs for disorders of the endocrine system - A61P 5/48: of the pancreatic hormones - A61P 5/50: for increasing or potentiating the activity of insulin - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - A61B 5/4255: {Intestines, colon or appendix} - A61M 2025/105: {having a balloon suitable for drug delivery, e.g. by using holes for delivery, drug coating or membranes} - A61M 2205/3633: thermally insulated - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D) - A61M: DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY (introducing media into or onto the bodies of animals A61D7/00; means for inserting tampons A61F13/26; devices for administering food or medicines orally A61J; containers for collecting, storing or administering blood or medical fluids A61J1/05); DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY (surgery A61B; chemical aspects of surgical articles A61L); DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR {(Electrotherapy, e.g. producing anaesthesia by the use of alternating or intermittent currents A61N1/36021)} - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract Embodiments provide swallowable devices, preparations and methods for delivering viable cells (VC) into the GI tract including GI wall tissue or other tissue site. Particular embodiments provide a swallowable device such as a capsule for delivering VC into an intestinal wall or other site. The VC can be contained within a tissue-penetrating shell disposed in the capsule that protects the VC as they pass through the GI tract until they are inserted into GI tract tissue or other location. The shell desirably has shape, size and material consistency to be contained in a swallowable capsule, delivered from the capsule into solid tissue by the application of force on the shell and biodegrade within the solid tissue to release the VC into the tissue. Within the shell or other structure the VC can be maintained in a viability-sustaining gel that preserves the viability of the VC for selected time periods. ## Claims ### Claim 1 An article for delivering viable cells into solid GI tissue of a patient, the article comprising: a shell configured for penetration into the GI solid tissue, the shell having a tissue penetrating end, a force application end, and a shell wall defining an interior of the shell; and a mass of viable cells within the interior of the shell; wherein the cells are present in a viability-sustaining gel; wherein the shell has a shape and material to: i) protect the viability of the cells from the external environment, ii) be contained in a swallowable capsule, iii) be delivered from the capsule into solid GI tissue by the application of force on the force application end, and iv) biodegrade within the solid tissue to release the viable cells into the solid GI tissue; and wherein the shell wall has fenestrations dimensioned to allow the passage of fluids and small molecules but to contain the cells and gel. ### Claim 2 (depends on 1) The article of claim 1, wherein the solid GI tissue is intestinal wall tissue, small intestine wall tissue or peritoneal wall tissue. ### Claim 3 (depends on 1) The article of claim 1, wherein the shell includes a moisture barrier on at least a portion of an interior surface of the shell wall, the moisture barrier configured to slow or prevent degradation of the shell due to moisture present in the interior of the shell, including moisture from the viability sustaining gel. ### Claim 4 (depends on 3) The article of claim 3, wherein the moisture barrier is configured to mechanically shear or degrade from external forces within tissue in the body when the shell wall biodegrades or the barrier is not fully supported by the shell wall. ### Claim 5 (depends on 3) The article of claim 3, wherein the moisture barrier comprises a coating. ### Claim 6 (depends on 1) The article of claim 1, wherein the viability-sustaining gel comprises at least one of an alginate, a hydrogel, a protein, a glycosaminoglycan, and polysaccharide. ### Claim 7 (depends on 1) The article of claim 1, further comprising a shock absorbing structure positioned on an interior surface of the shell opposite the tissue penetrating end, the shock absorbing structure configured to absorb a portion of the force imparted from the force application end when the article is inserted into solid tissue so as to minimize damage to the viable cells. ### Claim 8 (depends on 1) The article of claim 1, wherein a viscoelastic property of the gel is selected such that gel acts as a shock absorbing medium to absorb a portion of the force imparted from the force application end when the article is inserted into solid tissue so as to minimize damage to the viable cells. ### Claim 9 (depends on 8) The article of claim 8, wherein the viscoelastic property comprises a storage modulus in a range from about 200 to about 1000 Pascal's. ### Claim 10 (depends on 1) The article of claim 1, wherein the shell is configured to biodegrade over a time period of at least about 12 hours. ### Claim 11 (depends on 10) The article of claim 10, wherein the time period is in a range from 12 hours to 5 days. ### Claim 12 (depends on 1) The article of claim 1, wherein the shell comprises a biodegradable metal. ### Claim 13 (depends on 12) The article of claim 12, wherein the biodegradable metal is selected from a group consisting of magnesium, iron, and zinc. ### Claim 14 (depends on 1) The article of claim 1, wherein the shell comprises a biodegradable polymer. ### Claim 15 (depends on 14) The article of claim 14, wherein the biodegradable polymer is selected from a group consisting of poly lactic acid (PLA), poly lactic-co-glycolic acid (PGLA), and maltose. ### Claim 16 (depends on 1) The article of claim 1, wherein the fenestrations have a width in the range from 0.5 mm to 5 mm or an area in the range from 0.8 mm2 to 80 mm2. ### Claim 17 (depends on 1) The article of claim 1, wherein the fenestrations are shaped and dimensioned to function as an echogenic marker for the article when ultrasonically imaged. ### Claim 18 (depends on 17) The article of claim 17, wherein the fenestrations are configured to provide an indication of a degree of degradation when ultrasonically imaged. ### Claim 19 (depends on 1) The article of claim 1, wherein the cells are therapeutic cells, enteroendocrine cells, gastric enteroendocrine cells, or intestinal enteroendocrine cells. ### Claim 20 (depends on 19) The article of claim 19, wherein the viable cells are selected from a group consisting of pancreatic B-cells, L-cells, K-cells, G-cells, I cells, immune cells, stem cells, mesenchymal stem cells, and hematopoietic stem cells. ### Claim 21 (depends on 1) The article of claim 1, wherein the shell is thermally insulative to slow a thawing and reanimation of chilled or frozen cells due to heating as the article moves through the patient's intestinal tract. ### Claim 22 (depends on 1) The article of claim 1, wherein the shell comprises a material resistant to structural damage from freezing. ### Claim 23 (depends on 1) The article of claim 1, wherein the shell is only partially filed with the viability sustaining gel to provide room for expansion of the gel upon freezing such that article is not structurally damaged from expansion of the frozen gel. ### Claim 24 (depends on 1) The article of claim 1, wherein a volume of the shell interior is only partially filed with the viability sustaining gel to provide room for expansion of the gel upon freezing such that article is not structurally damaged from expansion of the frozen gel. ### Claim 25 (depends on 1) The article of claim 1, wherein the shell interior volume is about 50 to 90% filled with the gel. ### Claim 26 (depends on 25) The article of claim 25, wherein the shell interior volume is about 90 to 91% filled with the gel. ### Claim 27 (depends on 1) The article of claim 1, wherein the viability-sustaining gel is at least partially saturated with oxygen to preserve the viability of the cells. ### Claim 28 An article for delivering viable cells into solid GI tissue of a patient, the article comprising: a shell configured for penetration into the GI solid tissue, the shell having a tissue penetrating end, a force application end, and a shell wall defining an interior of the shell; and a mass of viable cells within the interior of the shell; wherein the cells are present in a viability-sustaining gel; wherein the shell has a shape and material to: i) protect the viability of the cells from the external environment, ii) be contained in a swallowable capsule, iii) be delivered from the capsule into solid GI tissue by the application of force on the force application end, and iv) biodegrade within the solid tissue to release the viable cells into the solid GI tissue; and wherein a viscoelastic property of the gel is selected such that gel acts as a shock absorbing medium to absorb a portion of the force imparted from the force application end when the article is inserted into solid tissue so as to minimize damage to the viable cells. ### Claim 29 (depends on 28) The article of claim 28, wherein the viscoelastic property comprises a storage modulus in a range from about 200 to about 1000 Pascal's. ### Claim 30 An article for delivering viable cells into solid GI tissue of a patient, the article comprising: a shell configured for penetration into the GI solid tissue, the shell having a tissue penetrating end, a force application end, and a shell wall defining an interior; and a mass of viable cells within the interior of the shell; wherein the cells are present in a viability-sustaining gel at least partially saturated with nitrogen or other inert gas to preserve the viability of the cells; and wherein the shell has a shape and material to: i) protect the viability of the cells from the external environment, ii) be contained in a swallowable capsule, iii) be delivered from the capsule into solid GI tissue by the application of force on the force application end, and iv) biodegrade within the solid tissue to release the viable cells into the solid GI tissue. ### Claim 31 (depends on 30) The article of claim 30, wherein the shell includes a moisture barrier on at least a portion of an interior surface of the shell wall, the moisture barrier configured to slow or prevent degradation of the shell due to moisture present in the interior defined by the shell wall, including moisture from the viability sustaining gel. ### Claim 32 (depends on 31) The article of claim 31, wherein the moisture barrier is configured to mechanically shear or degrade from external forces within tissue in the body when the shell wall biodegrades or the barrier is not fully supported by the shell wall. ### Claim 33 (depends on 30) The article of claim 30, wherein the shell is thermally insulative to slow a thawing and reanimation of chilled or frozen cells due to heating as the article moves through the patient's intestinal tract. ### Claim 34 (depends on 30) The article of claim 30, wherein a viscoelastic property of the gel is selected such that gel acts as a shock absorbing medium to absorb a portion of the force imparted from the force application end when the article is inserted into solid tissue so as to minimize damage to the viable cells.