Pyrrolobenzodiazepine—antibody conjugates
View Patent ↗Conjugates of specific PBD dimers with an antibody that binds to CD22, the antibody comprising a VH domain having the sequence according to SEQ ID NO. 1.
1. A conjugate of formula
wherein:
the drug loading is an integer from 1 to about 8;
Ab is an antibody that binds to CD22, the antibody comprising a VH domain having the sequence according to SEQ ID NO. 1.
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 of SEQ ID NO. 1 paired with SEQ ID NO. 2.
3. The conjugate according to claim 1 wherein the antibody in an intact antibody.
4. The conjugate according to claim 3 wherein the antibody comprises a heavy chain having the sequence of SEQ ID NO. 3 paired with a light chain having the sequence of SEQ ID NO. 4.
5. The conjugate according claim 4 wherein the antibody comprises two heavy chains having the sequence of SEQ ID NO. 3, each paired with a light chain having the sequence of SEQ ID NO. 4.
6. The conjugate according to claim 1 wherein the antibody is humanised, deimmunised or resurfaced.
7. The conjugate according to claim 1 , wherein the drug loading is 1, 2, 3, or 4.
8. A mixture of conjugates according to claim 1 , wherein the average value of the drug loading is about 2 to about 5.
9. A pharmaceutical composition comprising the conjugate of claim 1 and a pharmaceutically acceptable diluent, carrier or excipient.
10. The pharmaceutical composition of claim 9 further comprising a therapeutically effective amount of a chemotherapeutic agent.
11. A method of treating CD22 overexpressing cancers comprising administering to a patient the pharmaceutical composition of claim 9 .
12. The method of claim 11 wherein the patient is administered a chemotherapeutic agent, in combination with the conjugate.