Pyrrolobenzodiazepine-antibody conjugates
View Patent ↗Conjugates of specific PBD dimers with an antibody that that binds to CD19, the antibody comprising a VH domain having the sequence according to any one of SEQ ID NOs. 1, 2, 3, 4, 5 or 6, optionally further comprising a VL domain having the sequence according to any one of SEQ ID NOs. 7, 8, 9, 10, 11 or 12.
1. A conjugate of formula
wherein:
the drug loading is from 1 to about 8;
Ab is an antibody that binds to CD19, the antibody comprising a VH domain having the sequence according to any one of SEQ ID NOs. 1, 2, 3, 4, 5 or 6, optionally further comprising a VL domain having the sequence according to any one of SEQ ID NOs. 7, 8, 9, 10, 11 or 12.
2. The conjugate according to claim 1 wherein the antibody comprises a VH domain paired with a VL domain, the VH and VL domains having sequences selected from the group consisting of:
SEQ ID NO. 1 paired with any one of SEQ ID NOs. 7, 8, 9, 10, 11 or 12;
SEQ ID NO. 2 paired with any one of SEQ ID NOs. 7, 8, 9, 10, 11 or 12;
SEQ ID NO. 3 paired with any one of SEQ ID NOs. 7, 8, 9, 10, 11 or 12;
SEQ ID NO. 4 paired with any one of SEQ ID NOs. 7, 8, 9, 10, 11 or 12;
SEQ ID NO. 5 paired with any one of SEQ ID NOs. 7, 8, 9, 10, 11 or 12; and
SEQ ID NO. 6 paired with any one of SEQ ID NOs. 7, 8, 9, 10, 11 or 12.
3. The conjugate according to claim 2 wherein the paired VH and VL domains have the sequences of: SEQ ID NO. 1 paired with SEQ ID NO. 7, SEQ ID NO. 2 paired with SEQ ID NO. 8, SEQ ID NO. 3 paired with SEQ ID NO. 9, SEQ ID NO. 4 paired with SEQ ID NO. 10, SEQ ID NO. 5 paired with SEQ ID NO. 11, or SEQ ID NO. 6 paired with SEQ ID NO. 12.
4. The conjugate according claim 1 wherein the antibody in an intact antibody.
5. The conjugate according to claim 1 wherein the antibody is humanised, deimmunised or resurfaced.
6. The conjugate according to claim 1 , wherein the drug loading is 1, 2, 3, or 4.
7. A mixture of conjugates according to claim 1 , wherein the average value of the drug loading is about 2 to about 5.
8. A pharmaceutical composition comprising the conjugate of claim 1 and a pharmaceutically acceptable diluent, carrier or excipient.
9. The pharmaceutical composition of claim 8 further comprising a therapeutically effective amount of a chemotherapeutic agent.
10. A method of treating CD19 overexpressing cancers comprising administering to a patient the pharmaceutical composition of claim 8 .
11. The method of claim 10 wherein the patient is administered a chemotherapeutic agent, in combination with the conjugate.