Pyrrolobenzodiazepine-antibody conjugates

1. A conjugate of formula

ConjB:

 or ConjC

wherein:

the drug loading is from 1 to 8;

Ab is an antibody that binds to PSMA, the antibody comprising a VH domain having the sequence according to any one of SEQ ID NOs. 1, 3, 5, 7, 8, 9, or 10, optionally further comprising a VL domain having the sequence according to any one of SEQ ID NOs. 2, 4, 6, 11, 12, 13, 14, 15, 16, 17, or 18.

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. 2, 4, 6, 11, 12, 13, 14, 15, 16, 17, or 18;

SEQ ID NO. 3 paired with any one of SEQ ID NOs. 2, 4, 6, 11, 12, 13, 14, 15, 16, 17, or 18;

SEQ ID NO. 5 paired with any one of SEQ ID NOs. 2, 4, 6, 11, 12, 13, 14, 15, 16, 17, or 18;

SEQ ID NO. 7 paired with any one of SEQ ID NOs. 2, 4, 6, 11, 12, 13, 14, 15, 16, 17, or 18;

SEQ ID NO. 8 paired with any one of SEQ ID NOs. 2, 4, 6, 11, 12, 13, 14, 15, 16, 17, or 18;

SEQ ID NO. 9 paired with any one of SEQ ID NOs. 2, 4, 6, 11, 12, 13, 14, 15, 16, 17, or 18; or SEQ ID NO. 10 paired with any one of SEQ ID NOs. 2, 4, 6, 11, 12, 13, 14, 15, 16, 17, or 18.

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. 2, SEQ ID NO. 3 paired with SEQ ID NO. 4, SEQ ID NO. 5 paired with SEQ ID NO. 6, SEQ ID NO. 7 paired with SEQ ID NO. 11, SEQ ID NO. 7 paired with SEQ ID NO. 12, SEQ ID NO. 7 paired with SEQ ID NO. 13, SEQ ID NO. 7 paired with SEQ ID NO. 14, SEQ ID NO. 7 paired with SEQ ID NO. 15, SEQ ID NO. 7 paired with SEQ ID NO. 16, SEQ ID NO. 7 paired with SEQ ID NO. 17, SEQ ID NO. 7 paired with SEQ ID NO. 18, SEQ ID NO. 8 paired with SEQ ID NO. 11, SEQ ID NO. 8 paired with SEQ ID NO. 12, SEQ ID NO. 8 paired with SEQ ID NO. 13, SEQ ID NO. 8 paired with SEQ ID NO. 14, SEQ ID NO. 8 paired with SEQ ID NO. 15, SEQ ID NO. 8 paired with SEQ ID NO. 16, SEQ ID NO. 8 paired with SEQ ID NO. 17, SEQ ID NO. 8 paired with SEQ ID NO. 18, SEQ ID NO. 9 paired with SEQ ID NO. 11, SEQ ID NO. 9 paired with SEQ ID NO. 12, SEQ ID NO. 9 paired with SEQ ID NO. 13, SEQ ID NO. 9 paired with SEQ ID NO. 14, SEQ ID NO. 9 paired with SEQ ID NO. 15, SEQ ID NO. 9 paired with SEQ ID NO. 16, SEQ ID NO. 9 paired with SEQ ID NO. 17, SEQ ID NO. 9 paired with SEQ ID NO. 18, SEQ ID NO. 10 paired with SEQ ID NO. 11, SEQ ID NO. 10 paired with SEQ ID NO. 12, SEQ ID NO. 10 paired with SEQ ID NO. 13, SEQ ID NO. 10 paired with SEQ ID NO. 14, SEQ ID NO. 10 paired with SEQ ID NO. 15, SEQ ID NO. 10 paired with SEQ ID NO. 16, SEQ ID NO. 10 paired with SEQ ID NO. 17, or SEQ ID NO. 10 paired with SEQ ID NO. 18.

4. The conjugate according to 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 a therapeutically effective amount of 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 prostate cancer comprising administering to a patient the pharmaceutical composition of claim 8 .

11. The method of claim 10 wherein the patient is administered a therapeutically effective amount of a chemotherapeutic agent, in combination with the conjugate.