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US 9,173,959 B1Granted
Anti-DLL3 antibody drug conjugates
AssigneeStemcentrx, Inc.
InventorsRobert A. Stull, Laura Saunders, Scott J. Dylla, Orit Foord, David Liu, Michael Torgov, Hui Shao
Life of this patent
Estimating the term…
Abstract
Pharmaceutical compositions to treat proliferative disorders are provided.
Claims30
A pharmaceutical composition comprising:
- (a) an antibody drug conjugate of the formula M-[L-D]n, or a pharmaceutically acceptable salt thereof, wherein:
- M comprises an anti-DLL3 monoclonal antibody that specifically binds to an epitope within the DSL domain of a DLL3 protein set forth as SEQ ID NO:
- 3 or 4;
- L comprises a linker;
- D comprises a pyrrolobenzodiazepine (PBD);
- and
- n is an integer from 1 to 20;
- and
- (b) a pharmaceutically acceptable carrier.
6 more elements
A pharmaceutical composition comprising:
- (a) an antibody drug conjugate of the formula M-[L-D]n, or a pharmaceutically acceptable salt thereof, wherein:
- M comprises an anti-DLL3 monoclonal antibody;
- L comprises a linker;
- D 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, O—SO2—R, 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 a linker connected to a modulator or fragment or derivative thereof;
- 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;
- R2″, R6″, R7″, R9″, and X″ are as defined according to R2, R6, R7, R9, and X, respectively;
- 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
- X is selected from O, S, and N(H);
- and
- n is an integer from 1 to 20;
- and
- (b) a pharmaceutically acceptable carrier.
18 more elements
Dependencies are inferred from the claim text.