US 11,926,676 B2
Masked chimeric antigen receptor specific to tyrosine-protein kinase like 7 (PTK7) and immune cells expressing such
Jason Sagert, Cambridge, MA (US); Jui Dutta-Simmons, Cambridge, MA (US); and Jonathan Alexander Terrett, Cambridge, MA (US)
Assigned to CRISPR THERAPEUTICS AG, Zug (CH)
Filed by CRISPR THERAPEUTICS AG, Zug (CH)
Filed on May 6, 2021, as Appl. No. 17/313,121.
Claims priority of provisional application 63/020,794, filed on May 6, 2020.
Prior Publication US 2021/0347913 A1, Nov. 11, 2021
Int. Cl. C07K 16/40 (2006.01); A61K 35/17 (2015.01); A61K 38/00 (2006.01); A61K 39/00 (2006.01); A61P 35/00 (2006.01); C07K 7/08 (2006.01); C07K 14/47 (2006.01); C07K 14/705 (2006.01); C07K 14/725 (2006.01); C12N 5/0783 (2010.01)
CPC C07K 16/40 (2013.01) [A61K 35/17 (2013.01); A61P 35/00 (2018.01); C07K 7/08 (2013.01); C07K 14/47 (2013.01); C07K 14/7051 (2013.01); C07K 14/70517 (2013.01); C07K 14/70521 (2013.01); C07K 14/70578 (2013.01); C12N 5/0636 (2013.01); A61K 38/00 (2013.01); A61K 2039/505 (2013.01); A61K 2039/5156 (2013.01); A61K 2039/5158 (2013.01); C07K 2317/622 (2013.01); C07K 2317/72 (2013.01); C07K 2317/73 (2013.01); C07K 2317/76 (2013.01); C07K 2317/92 (2013.01); C07K 2319/02 (2013.01); C07K 2319/03 (2013.01); C07K 2319/30 (2013.01); C07K 2319/33 (2013.01); C07K 2319/50 (2013.01); C12N 2510/00 (2013.01)] 30 Claims
 
1. A masked chimeric antigen receptor (CAR) specific to tyrosine-protein kinase-like 7 (PTK7), the masked CAR comprising:
(i) an extracellular antigen binding domain, which comprises a single chain variable fragment (scFv) that binds PTK7 and a mask peptide linked to the N-terminus of the scFv via a protease cleavage site; and
(ii) one or more intracellular signaling domains,
wherein the mask peptide comprises the amino acid sequence selected from the group consisting of:
 
 (a)
 
 (SEQ ID NO: 1)
 
 EVAPGKRWFYNHVKQVPHLV,
 
 
 
 (b)
 
 (SEQ ID NO: 2)
 
 HEEVHMRPNKLSLTWAYTGPQLR,
and
(c) X1CX2X3X4X5X6X7X8X9X10X11X12X13, in which X1 is V, W, or absent; X2 is T, H, or Y; X3 is M, F, Y, I, or H; X4 is P, G, or V; X5 is P, N, S, Y, K, L, V, or A; X6 is S, T, W, A, H, R, or Q; X7 is P, T, V, H, I, M, A, F, or W; X8 is R, M, A, H, V, Y, or absent; X9 is S, Q, Y, T, P, A, M, or I; X10 is K, R, I, C, S, Q, H, or absent; X11 is V, T, R, L, F, W, or A; X12 is I, F, L, W, or H; and X13 is C, I, or M.