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:
![]() 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.
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