US 12,012,462 B2
Chimeric receptors to DLL3 and methods of use thereof
Michael John Giffin, Newbury Park, CA (US); Melissa Thomas, Palo Alto, CA (US); Christopher Murawsky, Roberts Creek (CA); Ryan B. Case, Alameda, CA (US); Lawren Wu, Foster City, CA (US); Jed J. Wiltzius, Winchester, MA (US); Ruben Alvarez Rodriguez, Los Angeles, CA (US); and Jun Feng, Los Angeles, CA (US)
Assigned to Amgen Inc., Thousand Oaks, CA (US)
Appl. No. 17/046,731
Filed by AMGEN INC., Thousand Oaks, CA (US); and KiTe Pharma, Inc., Santa Monica, CA (US)
PCT Filed Apr. 10, 2019, PCT No. PCT/US2019/026840
§ 371(c)(1), (2) Date Oct. 9, 2020,
PCT Pub. No. WO2019/200007, PCT Pub. Date Oct. 17, 2019.
Claims priority of provisional application 62/655,725, filed on Apr. 10, 2018.
Prior Publication US 2021/0163621 A1, Jun. 3, 2021
Int. Cl. C07K 16/30 (2006.01); A61K 39/00 (2006.01); A61P 35/00 (2006.01); C07K 14/705 (2006.01); C12N 15/86 (2006.01)
CPC C07K 16/30 (2013.01) [A61P 35/00 (2018.01); C07K 14/70517 (2013.01); C07K 14/70521 (2013.01); C12N 15/86 (2013.01); A61K 2039/505 (2013.01); C07K 2317/565 (2013.01); C07K 2317/622 (2013.01); C12N 2740/15041 (2013.01)] 14 Claims
 
1. A chimeric antigen receptor comprising
(i) an antigen binding molecule that specifically binds to DLL3, a costimulatory domain, and an activating domain that is a signaling domain of CD3 zeta, wherein the antigen binding molecule comprises:
a variable heavy chain region comprising complementary determining regions (“CDRs”) 1, 2, and 3 with amino acid sequences SEQ ID NO:42, SEQ ID NO:43, and SEQ ID NO:44, respectively, and a variable light chain region comprising CDRs 1, 2, and 3 with amino acid sequences SEQ ID NO:47, SEQ ID NO:48, and SEQ ID NO:49, respectively; or
a variable heavy chain region comprising complementary determining regions (“CDRs”) 1, 2, and 3 with amino acid sequences SEQ ID NO:52, SEQ ID NO:53, and SEQ ID NO:54, respectively, and a variable light chain region comprising CDRs 1, 2, and 3 with amino acid sequences SEQ ID NO:57, SEQ ID NO:58, and SEQ ID NO:59, respectively; or
a variable heavy chain region comprising complementary determining regions (“CDRs”) 1, 2, and 3 with amino acid sequences SEQ ID NO:62, SEQ ID NO:63, and SEQ ID NO:64, respectively, and a variable light chain region comprising CDRs 1, 2, and 3 with amino acid sequences SEQ ID NO:67, SEQ ID NO:68, and SEQ ID NO:69, respectively; or
a VH region of SEQ ID NO:41 and a VL region of SEQ ID NO:46, or
a VH region having at least 90% identity to the amino acid sequence of SEQ ID NO: 41 and a VL region having at least 90% identity to the amino acid sequence of SEQ ID NO:46, with the proviso that the VH region comprises a variable heavy chain CDR1 of SEQ ID NO: 42, a variable heavy chain CDR2 of SEQ ID NO: 43, and a variable heavy chain CDR3 of SEQ ID NO: 44, and the VL region comprises a variable light chain CDR1 of SEQ ID NO: 47, a variable light chain CDR2 of SEQ ID NO: 48, and a variable light chain CDR3 of SEQ ID NO: 49; or
a VH region of SEQ ID NO:51 and a VL region of SEQ ID NO:56, or
a VH region having at least 90% identity to the amino acid sequence of SEQ ID NO: 51 and a VL region having at least 90% identity to the amino acid sequence of SEQ ID NO:56, with the proviso that the VH region comprises a variable heavy chain CDR1 of SEQ ID NO: 52, a variable heavy chain CDR2 of SEQ ID NO: 53, and a variable heavy chain CDR3 of SEQ ID NO: 54, and the VL region comprises a variable light chain CDR1 of SEQ ID NO: 57, a variable light chain CDR2 of SEQ ID NO: 58, and a variable light chain CDR3 of SEQ ID NO: 59; or
a VH region of SEQ ID NO:61 and a VL region of SEQ ID NO:66, or
a VH region having at least 95% identity to the amino acid sequence of SEQ ID NO: 61 and a VL region having at least 90% identity to the amino acid sequence of SEQ ID NO:66, with the proviso that the VH region comprises a variable heavy chain CDR1 of SEQ ID NO: 62, a variable heavy chain CDR2 of SEQ ID NO: 63, and a variable heavy chain CDR3 of SEQ ID NO: 64, and the VL region comprises a variable light chain CDR1 of SEQ ID NO: 67, a variable light chain CDR2 of SEQ ID NO: 68, and a variable light chain CDR3 of SEQ ID NO: 69; and
wherein the VH and VL region is linked by at least one linker to at least one costimulatory domain, wherein the costimulatory domain is a CD28 costimulatory domain which comprises a sequence that differs at no more than 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, or 0 amino acid residues from the sequence of SEQ ID NO: 2, SEQ ID NO: 4, or SEQ ID NO: 4 in combination with SEQ ID NO: 6 or SEQ ID NO: 8, or a 4-1BB costimulatory domain which comprises a sequence that differs at no more than 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, or 0 amino acid residues from the sequence of SEQ ID NO: 16, or SEQ ID NO: 16 in combination with SEQ ID NO: 8.