US 12,071,477 B2
Anti-folate receptor alpha antibody conjugated with hemiasterlins
Ryan Stafford, Emeryville, CA (US); Alice Yam, Tiburon, CA (US); Xiaofan Li, Fremont, CA (US); Gang Yin, South San Francisco, CA (US); Toni Kline, San Francisco, CA (US); Cristina Abrahams, Burlingame, CA (US); and Venita De Almeida, San Carlos, CA (US)
Assigned to SUTRO BIOPHARMA, INC., South San Francisco, CA (US)
Appl. No. 16/648,130
Filed by SUTRO BIOPHARMA, INC., South San Francisco, CA (US)
PCT Filed Sep. 17, 2018, PCT No. PCT/US2018/051322
§ 371(c)(1), (2) Date Mar. 17, 2020,
PCT Pub. No. WO2019/055909, PCT Pub. Date Mar. 21, 2019.
Claims priority of provisional application 62/560,064, filed on Sep. 18, 2017.
Prior Publication US 2020/0353076 A1, Nov. 12, 2020
This patent is subject to a terminal disclaimer.
Int. Cl. C07K 16/28 (2006.01); A61K 9/19 (2006.01); A61K 38/06 (2006.01); A61K 39/395 (2006.01); A61K 47/68 (2017.01); A61P 35/00 (2006.01); A61K 31/395 (2006.01); A61K 31/537 (2006.01); A61K 38/08 (2019.01); A61K 38/12 (2006.01); A61K 47/64 (2017.01); C07D 487/00 (2006.01)
CPC C07K 16/28 (2013.01) [A61K 9/19 (2013.01); A61K 38/06 (2013.01); A61K 39/3955 (2013.01); A61K 47/6811 (2017.08); A61K 47/6849 (2017.08); A61K 47/6851 (2017.08); A61K 47/6889 (2017.08); A61P 35/00 (2018.01); A61K 31/537 (2013.01); A61K 31/5545 (2017.08); A61K 38/08 (2013.01); A61K 38/12 (2013.01); A61K 47/6425 (2017.08); A61K 47/6803 (2017.08); A61K 47/6877 (2017.08); C07D 487/00 (2013.01); C07K 2317/60 (2013.01); C07K 2317/92 (2013.01)] 26 Claims
 
1. An antibody conjugate comprising an antibody that specifically binds to folate receptor alpha (FOLR1) linked site-specifically to at least one payload moiety, wherein the antibody conjugate is a compound according to formula E1:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt, solvate, stereoisomer, or tautomer thereof, wherein:
Ar is a divalent five- or six-membered, substituted or unsubstituted, monocyclic aryl or heteroaryl ring or a divalent eight-, nine- or ten-membered, substituted or unsubstituted, fused bicyclic aryl or heteroaryl ring;
L is absent or —CH2—;
X is

OG Complex Work Unit Chemistry
W1, W2, W3, W4, and W5 are each independently a single bond, absent, or a divalent attaching group;
EG is absent or an eliminator group;
each RT is a release trigger group, wherein each RT is optional;
RT1 is a release trigger group, or a cleavable linker, or RT1 is absent;
HP is a single bond, absent, or a divalent hydrophilic group;
HP1 is a single bond, absent, a divalent hydrophilic group, or

OG Complex Work Unit Chemistry
where RHP is a monovalent hydrophilic group;
SG is a single bond, absent, or a divalent spacer group;
R is a divalent residue of a terminal conjugating group; and
COMP is a residue of an antibody chain of FOLR1;
wherein the antibody comprises: three heavy chain CDRs and three light chain CDRs from one of the following VH/VL pairs: SEQ ID NOs: 323/367, SEQ ID NOs: 308/367, SEQ ID NOs: 309/367, SEQ ID NOs: 310/367, SEQ ID NOs: 311/367, SEQ ID NOs: 312/367, SEQ ID NOs: 313/367, SEQ ID NOs: 314/367, SEQ ID NOs: 315/367, SEQ ID NOs: 316/367, SEQ ID NOs: 317/367, SEQ ID NOs: 318/367, SEQ ID NOs: 319/367, SEQ ID NOs: 320/367, SEQ ID NOs: 321/367, SEQ ID NOs: 322/367, SEQ ID NOs: 324/367, SEQ ID NOs: 325/367, SEQ ID NOs: 326/367, SEQ ID NOs: 327/367, SEQ ID NOs: 328/367, SEQ ID NOs: 329/367, SEQ ID NOS: 330/367, SEQ ID NOs: 331/367, SEQ ID NOs: 332/367, SEQ ID NOs: 333/367, SEQ ID NOs: 334/367, SEQ ID NOs: 335/367, SEQ ID NOs: 336/367, SEQ ID NOs: 337/367, SEQ ID NOs: 338/367, SEQ ID NOs: 339/367, SEQ ID NOs: 340/367, SEQ ID NOs: 341/367, SEQ ID NOs: 342/367, SEQ ID NOs: 343/367, SEQ ID NOs: 344/367, SEQ ID NOs: 345/367, SEQ ID NOs: 346/367, SEQ ID NOs: 347/367, SEQ ID NOs: 348/367, SEQ ID NOs: 349/367, SEQ ID NOs: 350/367, SEQ ID NOs: 351/367, SEQ ID NOs: 352/367, SEQ ID NOs: 353/367, SEQ ID NOs: 354/367, SEQ ID NOs: 355/367, SEQ ID NOs: 356/367, SEQ ID NOs: 357/367, SEQ ID NOs: 358/367, SEQ ID NOs: 359/367, SEQ ID NOs: 360/367, SEQ ID NOs: 361/367, SEQ ID NOs: 362/367, SEQ ID NOs: 363/368, SEQ ID NOs: 364/368, SEQ ID NOs: 365/369, or SEQ ID NOs: 366/369, linked site-specifically to at least one payload moiety by one or more non-natural amino acids.