# US 12,213,998 B2 · Adipose tissue-derived stromal stem cells for use in treating refractory complex perianal fistulas in Crohn's disease > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,213,998 B2 - Document ID: US12213998B2 - Status: Granted - Kind: B2 - Application number: 17/671,479 - Filed: 2022-02-14 - Published: 2022-08-11 - Granted: 2025-02-04 - Earliest claimed: 2016-03-14 - Assignees: Takeda Pharmaceutical Company Limited - Applicants: Takeda Pharmaceutical Company Limited - Inventors: Eduardo Bravo; Maria Pascual - Web page: https://patentgrep.com/patent/US12213998B2 ## CPC - A61K 35/35: Fat tissue; Adipocytes; Stromal cells; Connective tissues (adipose-derived stem cells A61K35/28; collagen A61K38/39) - A61K 35/28: Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells - A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system - A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants - A61P 9/14: Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers - 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) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract Provided herein are expanded allogeneic adipose tissue-derived stromal stem cells for use in treating complex perianal fistulas in Crohn's Disease. ## Claims ### Claim 1 A method of treating a complex perianal fistula in a subject having Crohn's disease comprising administering a therapeutic amount of a population of expanded allogeneic adipose tissue-derived stem cells to the subject, wherein: (i) the fistula comprises a complex fistula with 1 or 2 internal openings and/or 2 or 3 external openings; (ii) the therapeutic amount is a fixed dose of expanded allogeneic adipose tissue-derive stem cells which is administered to the subject in a single administration, wherein a further administration is excluded, wherein each fistula tract receives at least a proportion of this dose and wherein approximately half of the dose is injected into the tissue surrounding the internal opening or openings and the other half is injected into the fistula walls along the fistula tracts; and (iii) the fixed dose is about 120 million expanded allogeneic adipose tissue-derived stem cells. ### Claim 2 (depends on 1) The method according to claim 1, wherein the fistula comprises 2 internal openings. ### Claim 3 (depends on 1) The method according to claim 1, wherein the fistula comprises 2 or 3 external openings. ### Claim 4 (depends on 1) The method according to claim 1, wherein the fistula has 2 internal and 3 external openings. ### Claim 5 (depends on 1) The method according to claim 1, wherein the fistula comprises 2 or 3 tracts. ### Claim 6 (depends on 1) The method according to claim 1, wherein the subject has non-active or mildly active luminal Crohn's disease. ### Claim 7 (depends on 1) The method according to claim 1, wherein the complex perianal fistula has shown an inadequate response to at least one conventional or biologic therapy. ### Claim 8 (depends on 7) The method according to claim 7, wherein the complex perianal fistula has shown an inadequate response to one or more of antibiotics, immunosuppressants or anti-TNF therapies. ### Claim 9 (depends on 1) The method according to claim 1, wherein administering the therapeutic amount of the population of expanded allogeneic adipose tissue-derived stem cells induces combined remission at week 24. ### Claim 10 (depends on 1) The method according to claim 1, wherein administering the therapeutic amount of the population of expanded allogeneic adipose tissue-derived stem cells to the subject induces clinical remission within 18 weeks. ### Claim 11 (depends on 1) The method according to claim 1, wherein administering the therapeutic amount of the population of expanded allogeneic adipose tissue-derived stem cells to the subject induces clinical remission at week 24. ### Claim 12 (depends on 1) The method according to claim 1, wherein an improvement in a Perianal Disease Activity Index (PDAI) is achieved within 24 weeks. ### Claim 13 (depends on 12) The method according to claim 12, wherein the improvement in the PDAI is an improvement of greater than 1.5 PDAI points. ### Claim 14 (depends on 12) The method according to claim 12, wherein the improvement in the PDAI is an improvement of at least two PDAI points. ### Claim 15 (depends on 1) The method according to claim 1, wherein an improvement in Perianal Disease Activity Index (PDAI) is achieved at week 18. ### Claim 16 (depends on 15) The method according to claim 15, wherein the improvement in the PDAI is an improvement of greater than 1.5 PDAI points. ### Claim 17 (depends on 15) The method according to claim 15, wherein the improvement in the PDAI is an improvement of at least two PDAI points. ### Claim 18 (depends on 1) The method according to claim 1, wherein the subject receives neither or both of an anti-TNF therapy and an immunosuppressant therapy. ### Claim 19 (depends on 1) The method according to claim 1, wherein the fistula is monitored by magnetic resonance imaging (MRI). ### Claim 20 (depends on 1) The method according to claim 1, wherein the expanded allogeneic adipose tissue-derived stem cells express four or more of HLAI, CD29, CD44, CD59, CD73, CD90, and CD 105; and do not express four or more of HLAII, CD11b, CD11c, CD14, CD45, CD31, CD34, and CD80.