US 12,226,490 B2
Anti-ROR1 antibody conjugates, compositions comprising anti ROR1 antibody conjugates, and methods of making and using anti-ROR1 antibody conjugates preliminary class
Amandeep Gakhal, San Mateo, CA (US); Abigail Yu, San Jose, CA (US); Ryan Stafford, Foster City, CA (US); Jeffrey Hanson, Oakland, CA (US); Alice Yam, Belmont, CA (US); Krishna Bajjuri, Union City, CA (US); Andreas Maderna, Walnut Creek, CA (US); Cristina Abrahams, Burlingame, CA (US); Xiaofan Li, Belmont, CA (US); Gang Yin, South San Francisco, CA (US); Miao Wen, Union City, CA (US); Kristin Bedard, Bellevue, WA (US); Daniel Calarese, Millbrae, CA (US); and Helena Kiefel, South San Francisco, CA (US)
Assigned to Sutro Biopharma, Inc., South San Francisco, CA (US)
Filed by Sutro Biopharma, Inc., South San Francisco, CA (US)
Filed on Jul. 10, 2023, as Appl. No. 18/349,337.
Application 18/349,337 is a continuation of application No. PCT/US2023/026769, filed on Jun. 30, 2023.
Claims priority of provisional application 63/357,442, filed on Jun. 30, 2022.
Claims priority of provisional application 63/389,741, filed on Jul. 15, 2022.
Claims priority of provisional application 63/382,262, filed on Nov. 3, 2022.
Claims priority of provisional application 63/487,706, filed on Mar. 1, 2023.
Claims priority of provisional application 63/489,926, filed on Mar. 13, 2023.
Claims priority of provisional application 63/495,635, filed on Apr. 12, 2023.
Prior Publication US 2024/0058467 A1, Feb. 22, 2024
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 47/68 (2017.01); A61K 31/502 (2006.01); A61P 35/00 (2006.01)
CPC A61K 47/6869 (2017.08) [A61K 31/502 (2013.01); A61K 47/6803 (2017.08); A61K 47/6805 (2017.08); A61K 47/6809 (2017.08); A61K 47/6849 (2017.08); A61K 47/6889 (2017.08); A61P 35/00 (2018.01)] 38 Claims
 
1. An antibody conjugate comprising an antibody that specifically binds to receptor tyrosine kinase orphan receptor 1 (ROR1) linked site-specifically to at least one payload moiety, wherein the antibody comprises one or more non-natural amino acids and wherein the antibody conjugate is according to the structure of Formula I:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein
COMP is a residue of the anti-ROR1 antibody comprising one or more non-natural amino acids;
L1 is —C1-6 alkylene-;
Y is —X1—C1-6 alkylene-[X1—C1-6 alkylene]n-[X1]p—, —X1—C2-6 alkenylene-[X1—C2-6 alkenylene]n-[X1]p—, —X1—C2-6 alkynylene-[X1—C2-6 alkynylene]n-[X1]p—, wherein at least one alkylene, alkenylene or alkynylene in Y is substituted with one or more substituents selected from R50; and
wherein the alkylene, alkenylene, or alkynylene in Y is optionally substituted with one or more substituents selected from R51;
R50 is —C1-6 alkylene-X2—[C1-6 alkylene]m-POLY, —C2-6 alkenylene-X2—[C2-6 alkenylene]m-POLY, or —C2-6 alkynylene-X2—[C2-6 alkynylene]m-POLY, wherein each alkylene, alkenylene or alkynylene of R50 is optionally substituted with one or more substituents selected from halogen, —CN, —NO2, —OH, —N(R10)2, —C(O)N(R10)2, —C(O)—, —C(S)—, —C(O)OCH2C6H5, —NHC(O)OCH2C6H5, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-12 carbocycle, 3- to 12-membered heterocycle, and C1-10 haloalkyl;
R51 is independently selected from halogen, —CN, —NO2, —OH, —N(R10)2, —C(O)N(R10)2, —C(O)—, —C(S)—, —C(O)OCH2C6H5, —NHC(O)OCH2C6H5, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-12 carbocycle, 3- to 12-membered heterocycle, and C1-10 haloalkyl;
X1 and X2 are independently selected from —C(O)— and —N(R10)C(O)—;
R10 is independently selected at each occurrence from hydrogen, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-12 carbocycle, 3- to 12-membered heterocycle, and C1-10 haloalkyl;
POLY is a water-soluble polymer;
n is an integer selected from zero, one, two, and three;
m is an integer selected from zero and one;
p is an integer selected from zero and one;
Su is a hexose form of a monosaccharide;
D is a drug moiety; and
RL is a reactive group residue.