US 12,246,004 B2
Therapeutic treatment of microsatellite unstable cancers
Francisca Vazquez, Cambridge, MA (US); Adam Bass, Boston, MA (US); Tsukasa Shibue, Cambridge, MA (US); Edmond Chan, Boston, MA (US); James McFarland, Cambridge, MA (US); Mahmoud Ghandi, Cambridge, MA (US); and Aviad Tsherniak, Cambridge, MA (US)
Assigned to THE BROAD INSTITUTE, INC., Cambridge, MA (US); INSTITUTO CARLOS SLIM DE LA SALUD, A.C., D.F. (MX); and DANA-FARBER CANCER INSTITUTE, INC., Boston, MA (US)
Appl. No. 15/734,131
Filed by THE BROAD INSTITUTE, INC., Cambridge, MA (US); DANA-FARBER CANCER INSTITUTE, INC., Boston, MA (US); and INSTITUTO CARLOS SLIM DE LA SALUD, A.C., Colonia Granada Ampliacion (MX)
PCT Filed Jun. 3, 2019, PCT No. PCT/US2019/035130
§ 371(c)(1), (2) Date Dec. 1, 2020,
PCT Pub. No. WO2019/236448, PCT Pub. Date Dec. 12, 2019.
Claims priority of provisional application 62/853,412, filed on May 28, 2019.
Claims priority of provisional application 62/680,322, filed on Jun. 4, 2018.
Prior Publication US 2022/0133693 A1, May 5, 2022
Int. Cl. A61K 31/7105 (2006.01); A61K 31/4015 (2006.01); A61K 31/4025 (2006.01); A61K 31/473 (2006.01); A61K 31/497 (2006.01); A61K 31/519 (2006.01); A61K 31/5377 (2006.01); A61K 31/585 (2006.01); A61P 35/00 (2006.01); C12Q 1/68 (2018.01); C12Q 1/686 (2018.01); C12Q 1/6886 (2018.01)
CPC A61K 31/4025 (2013.01) [A61K 31/4015 (2013.01); A61K 31/473 (2013.01); A61K 31/497 (2013.01); A61K 31/519 (2013.01); A61K 31/5377 (2013.01); A61K 31/585 (2013.01); A61K 31/7105 (2013.01); A61P 35/00 (2018.01); C12Q 1/686 (2013.01); C12Q 1/6886 (2013.01); C12Q 2600/106 (2013.01)] 10 Claims
 
1. A method for treating a subject having or at risk of developing a cancer that exhibits microsatellite instability (MSI) and/or impaired mismatch repair (MMR), the method comprising:
(a) obtaining a sample from a subject having or at risk of developing a cancer that exhibits MSI and/or impaired MMR, wherein the subject has not responded to a previously administered programmed cell death 1 (PD-1) inhibitor immunotherapy;
(b) identifying the presence or absence in the sample of MSI and/or impaired MMR; (c)
(c) selecting a WRN inhibitor as a treatment for the subject if MSI and/or impaired MMR is identified in the sample, thereby selecting a treatment for the subject having or at risk of developing a cancer that exhibits MSI and/or impaired MMR; and
(d) administering the selected WRN inhibitor to the subject.