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US 9,867,887 B1Granted
Anti-DLL3 antibody drug conjugates
AssigneeAbbvie Stemcentrx LLC
InventorsRobert A. Stull, Laura Saunders, Scott J. Dylla, Orit Foord, David Liu, Michael Torgov, Hui Shao
Life of this patent
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Abstract
Novel modulators, including antibodies and derivatives thereof, and methods of using such modulators to treat proliferative disorders are provided.
Claims30
A pharmaceutical composition comprising:
- (a) an anti-DLL3 antibody, or a pharmaceutically acceptable salt thereof, wherein the anti-DLL3 antibody comprises a light chain variable region set forth as SEQ ID NO:
- 212 and a heavy chain variable region set forth as SEQ ID NO:
- 213, and wherein the anti-DLL3 antibody is conjugated to one or more cytotoxic agents;
- and
- (b) a pharmaceutically acceptable carrier.
2 more elements
A pharmaceutical composition comprising:
- (a) an antibody drug conjugate, or a pharmaceutically acceptable salt thereof, comprising a humanized anti-DLL3 antibody conjugated to one or more cytotoxic agents via a linker, wherein the humanized anti-DLL3 antibody comprises a light chain variable region set forth as SEQ ID NO:
- 212 and a heavy chain variable region set forth as SEQ ID NO:
- 213;
- and wherein the cytotoxic agent comprises a pyrrolobenzodiazepine (PBD) comprising the formula AC:
- wherein:
- the dotted lines indicate the optional presence of a double bond, and wherein only one of the dotted lines in a given ring can be a double bond;
- R2 is selected from H, OH, ═O, ═CH2, CN, R, OR, ═CH—RD, ═C(RD)2, OSO2R, CO2R, COR, and halo, where RD is selected from R, CO2R, COR, CHO, CO2H, and halo;
- R6 and R9 are each independently selected from H, R, OH, OR, SH, SR, NH2, NHR, NRR′, NO2, Me3Sn and halo;
- R7 is selected from H, R, OH, OR, SH, SR, NH2, NHR, NRR′, NO2, Me3Sn and halo;
- R10 is the linker connected to the anti-DLL3 antibody;
- Q is selected from O, S and NH;
- R11 is either H, or R or, where Q is O, SO3M, where M is a metal cation;
- R and R′ are each independently selected from optionally substituted C1-12 alkyl, C3-20 heterocyclyl and C5-20 aryl groups, and optionally in relation to the group NRR′, R and R′ together with the nitrogen atom to which they are attached form an optionally substituted 4-, 5-, 6- or 7-membered heterocyclic ring;
- X is selected from O, S, and N(H);
- R2″, R6″, R7″, R9″, and X″ are as defined according to R2, R6, R7, R9, and X, respectively;
- and
- R″ is a C3-12 alkylene group, which comprises a chain optionally interrupted by one or more heteroatoms, one or more rings, or both one or more heteroatoms and one or more rings, wherein the optional one or more rings are optionally substituted;
- and
- (b) a pharmaceutically acceptable carrier.
16 more elements
Dependencies are inferred from the claim text.