US 11,939,596 B2
Processes for production of tumor infiltrating lymphocytes and uses of same in immunotherapy
Seth Wardell, Tampa, FL (US); and James Bender, Rancho Santa Margarita, CA (US)
Assigned to Iovance Biotherapeutics, Inc., San Carlos, CA (US)
Filed by Iovance Biotherapeutics, Inc., San Carlos, CA (US)
Filed on Aug. 30, 2022, as Appl. No. 17/823,445.
Application 17/823,445 is a continuation of application No. 17/147,412, filed on Jan. 12, 2021.
Application 17/147,412 is a continuation of application No. 17/041,305, previously published as PCT/US2018/040474, filed on Jun. 29, 2018.
Application 17/041,305 is a continuation of application No. 15/940,901, filed on Mar. 29, 2018, granted, now 10,918,666, issued on Feb. 16, 2021.
Application 17/147,412 is a continuation of application No. 17/110,179, filed on Dec. 2, 2020.
Application 17/110,179 is a continuation in part of application No. 15/940,901, filed on Mar. 29, 2018, granted, now 10,918,666, issued on Feb. 16, 2021.
Application 15/940,901 is a continuation in part of application No. 15/863,634, filed on Jan. 5, 2018, granted, now 10,894,063, issued on Jan. 19, 2021.
Claims priority of provisional application 62/596,374, filed on Dec. 8, 2017.
Claims priority of provisional application 62/582,874, filed on Nov. 7, 2017.
Claims priority of provisional application 62/577,655, filed on Oct. 26, 2017.
Claims priority of provisional application 62/567,121, filed on Oct. 2, 2017.
Claims priority of provisional application 62/559,374, filed on Sep. 15, 2017.
Claims priority of provisional application 62/554,538, filed on Sep. 5, 2017.
Claims priority of provisional application 62/548,306, filed on Aug. 21, 2017.
Claims priority of provisional application 62/539,410, filed on Jul. 31, 2017.
Claims priority of provisional application 62/478,506, filed on Mar. 29, 2017.
Prior Publication US 2023/0013765 A1, Jan. 19, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. C12N 5/0783 (2010.01); A01N 1/02 (2006.01); A61K 9/00 (2006.01); A61K 31/675 (2006.01); A61K 31/7076 (2006.01); A61K 35/17 (2015.01); A61K 38/20 (2006.01); A61P 35/00 (2006.01); C12N 5/078 (2010.01); A61K 38/21 (2006.01); A61K 39/00 (2006.01)
CPC C12N 5/0636 (2013.01) [A01N 1/0284 (2013.01); A61K 9/0019 (2013.01); A61K 31/675 (2013.01); A61K 31/7076 (2013.01); A61K 35/17 (2013.01); A61K 38/2013 (2013.01); A61P 35/00 (2018.01); C12N 5/0634 (2013.01); C12N 5/0638 (2013.01); A61K 38/217 (2013.01); A61K 39/0011 (2013.01); A61K 2039/5154 (2013.01); A61K 2039/5156 (2013.01); A61K 2039/5158 (2013.01); A61K 2039/55533 (2013.01); C12N 2501/04 (2013.01); C12N 2501/2302 (2013.01); C12N 2501/2315 (2013.01); C12N 2501/2321 (2013.01); C12N 2501/24 (2013.01); C12N 2501/603 (2013.01); C12N 2502/11 (2013.01); C12N 2506/30 (2013.01)] 30 Claims
 
1. A method for expanding tumor infiltrating lymphocytes (TILs) into a therapeutic population of TILs, the method comprising:
(a) performing a first expansion by (i) thawing cryopreserved dissociated tumor materials comprising a first population of TILs from a tumor that was resected from a subject with cancer, dissociated after the resection, and cryopreserved after the dissociation, and (ii) culturing the first population of TILs in a cell culture medium comprising IL-2, and optionally OKT-3, to produce a second population of TILs, wherein the first expansion is performed in a closed system providing a first gas-permeable surface area, wherein the first expansion is performed for about 3-14 days to obtain the second population of TILs;
(b) performing a second expansion by supplementing the cell culture medium of the second population of TILs with additional IL-2, optionally OKT-3, and antigen presenting cells (APCs), to produce a third population of TILs, wherein the second expansion is performed for about 7-14 days to obtain the third population of TILs, wherein the second expansion is performed in the closed system providing a second gas-permeable surface area, and wherein the transition from step (a) to step (b) occurs without opening the closed system; and
(c) harvesting the third population of TILs, wherein the harvested third population of TILs is a therapeutic population of TILs, and wherein the transition from step (b) to step (c) occurs without opening the closed system.