US 11,965,025 B2
Method of treating solid cancers with bispecific interleukin-anti-TCRß molecules
Seng-Lai Tan, Sudbury, MA (US); Brian Edward Vash, Cambridge, MA (US); Jonathan Hsu, Waltham, MA (US); Dilini Charmain Gunasekera, Cambridge, MA (US); Sangeetha Sagar Palakurthi, East Walpole, MA (US); and Andreas Loew, Boston, MA (US)
Assigned to Marengo Therapeutics, Inc., Cambridge, MA (US)
Filed by Marengo Therapeutics, Inc., Cambridge, MA (US)
Filed on Aug. 18, 2022, as Appl. No. 17/820,794.
Application 17/820,794 is a continuation of application No. 17/256,917, granted, now 11,845,797, previously published as PCT/US2019/040592, filed on Jul. 3, 2019.
Claims priority of provisional application 62/693,653, filed on Jul. 3, 2018.
Claims priority of provisional application 62/737,829, filed on Sep. 27, 2018.
Claims priority of provisional application 62/788,674, filed on Jan. 4, 2019.
Claims priority of provisional application 62/808,700, filed on Feb. 21, 2019.
Prior Publication US 2023/0272074 A1, Aug. 31, 2023
Int. Cl. C07K 16/28 (2006.01); A61K 35/17 (2015.01); A61K 39/00 (2006.01); A61P 35/00 (2006.01); C12N 5/078 (2010.01)
CPC C07K 16/2809 (2013.01) [A61K 35/17 (2013.01); A61P 35/00 (2018.01); C07K 16/2803 (2013.01); C07K 16/283 (2013.01); C07K 16/2878 (2013.01); C12N 5/0634 (2013.01); A61K 2039/505 (2013.01); C07K 2317/24 (2013.01); C07K 2317/31 (2013.01); C07K 2317/55 (2013.01); C07K 2317/622 (2013.01); C07K 2317/92 (2013.01)] 26 Claims
 
1. A method of treating a solid cancer in a human subject in need thereof, wherein the solid cancer is a solid cancer selected from the group consisting of colon cancer, breast cancer, renal cancer, melanoma, prostate cancer, lung cancer, rectal cancer, colorectal cancer and cervical cancer, the method comprising administering a therapeutically effective amount of a pharmaceutical composition comprising a multispecific molecule,
wherein the multispecific molecule comprises a first domain that binds to a first target molecule expressed by a subset of T cells of the human subject and a second domain that binds to a second target molecule expressed by T cells of the human subject;
wherein the first target molecule is a human T cell receptor beta chain (TCR(3) subfamily member;
wherein the multispecific molecule is a TCR agonist;
wherein the second domain comprises a cytokine, wherein
(i) the cytokine is a human IL-2 having a sequence with at least 90% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 2191, 2270, 2280,
(ii) the cytokine is a human IL-12 having a sequence with at least 90% sequence identity to SEQ ID NO: 2290;
(iii) the cytokine is a human IL-15 having a sequence with at least 90% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 2170 and 2320, or
(iv) the cytokine is a human IL-21 having a sequence with at least 90% sequence identity to SEQ ID NO: 2193;
wherein the multispecific molecule binds to a human T cell receptor beta variable region (TCRβV) of the human TCRβ expressed by the subset of T cells of the human subject; and
wherein binding of the first domain to the TCRβV and binding of the second domain to the second target molecule promote the subset of T cells to kill cancer cells.