Anti-cd22 antibodies and immunoconjugates

An immunoconjugate of formula Ab-(L-D)p, wherein:

• (a) Ab is an antibody that binds CD22;
• (b) L is a linker;
• (c) D is a cytotoxic agent;
• and
• (d) p ranges from 1-8;
• wherein D is a pyrrolobenzodiazepine of Formula A:
• wherein the wavy line indicates a covalent attachment site to the linker;
• the dotted lines indicate the optional presence of a double bond between C1 and C2 or C2 and C3;
• R2 is independently selected from H, OH, ═O, ═CH2, CN, R, OR, ═CH—RD, ═C(RD)2, O—SO2-R, CO2R and COR, and optionally further selected from halo or dihalo, wherein RD is independently selected from R, CO2R, COR, CHO, CO2H, and halo;
• R6 and R9 are independently selected from H, R, OH, OR, SH, SR, NH2, NHR, NRR′, NO2, Me3 Sn and halo;
• R7 is independently selected from H, R, OH, OR, SH, SR, NH2, NHR, NRR′, NO2, Me3Sn and halo;
• Q is independently 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;
• R12, R16, R19 and R17 are as defined for R2, R6, R9 and R7 respectively;
• R″ is a C3-12 alkylene group, which chain may be interrupted by one or more heteroatoms and/or aromatic rings that are optionally substituted;
• and
• X and X′ are independently selected from O, S and N(H);
• and wherein the antibody comprises:
• (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO:
• 9, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO:
• 10, (iii) HVR-H3 comprising the amino acid sequence of SEQ ID NO:
• 11, (iv) HVR-L1 comprising an amino acid sequence selected from SEQ ID NOs:
• 12 and 15 to 22, (v) HVR-L2 comprising the amino acid sequence of SEQ ID NO:
• 13, and (vi) HVR-L3 comprising the amino acid sequence of SEQ ID NO:
• 14.

An immunoconjugate having a formula selected from:

• wherein Ab is an antibody comprising (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO:
• 9, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO:
• 10, (iii) HVR-H3 comprising the amino acid sequence of SEQ ID NO:
• 11, (iv) HVR-L1 comprising the amino acid sequence of SEQ ID NO:
• 15, (v) HVR-L2 comprising the amino acid sequence of SEQ ID NO:
• 13, and (vi) HVR-L3 comprising the amino acid sequence of SEQ ID NO:
• 14;
• and wherein p ranges from 1 to 3.

A method for treating an individual having a CD22-positive cancer, the method comprising administering to the individual an effective amount of an immunoconjugate of formula Ab-(L-D)p, wherein:

• (a) Ab is an antibody that binds CD22;
• (b) L is a linker;
• (c) D is a cytotoxic agent;
• and
• (d) p ranges from 1-8;
• wherein D is a pyrrolobenzodiazepine of Formula A:
• wherein the wavy line indicates a covalent attachment site to the linker;
• the dotted lines indicate the optional presence of a double bond between C1 and C2 or C2 and C3;
• R2 is independently selected from H, OH, ═O, ═CH2, CN, R, OR, ═CH—RD, ═C(RD)2, O—SO2-R, CO2R and COR, and optionally further selected from halo or dihalo, wherein RD is independently selected from R, CO2R, COR, CHO, CO2H, and halo;
• R6 and R9 are independently selected from H, R, OH, OR, SH, SR, NH2, NHR, NRR′, NO2, Me3 Sn and halo;
• R7 is independently selected from H, R, OH, OR, SH, SR, NH2, NHR, NRR′, NO2, Me3Sn and halo;
• Q is independently 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;
• R12, R16, R19 and R17 are as defined for R2, R6, R9 and R7 respectively;
• R″ is a C3-12 alkylene group, which chain may be interrupted by one or more heteroatoms and/or aromatic rings that are optionally substituted;
• and X and X′ are independently selected from O, S and N(H);
• and wherein the antibody comprises:
• (i) HVR-H1 comprising the amino acid sequence of SEQ ID NO:
• 9, (ii) HVR-H2 comprising the amino acid sequence of SEQ ID NO:
• 10, (iii) HVR-H3 comprising the amino acid sequence of SEQ ID NO:
• 11, (iv) HVR-L1 comprising an amino acid sequence selected from SEQ ID NOs:
• 12 and 15 to 22, (v) HVR-L2 comprising the amino acid sequence of SEQ ID NO:
• 13, and (vi) HVR-L3 comprising the amino acid sequence of SEQ ID NO:
• 14.