Pyrrolobenzodiazepine-anti-CD22 antibody conjugates
Conjugates of an isolated humanized, anti-CD22 antibody with PBD dimers.
1. A conjugate of formula ConjA:
wherein Ab is an antibody that binds to CD22, the antibody comprising a VH domain having the amino acid sequence according to SEQ ID NO. 1 and a VL domain having the amino acid sequence of SEQ ID NO. 2; and wherein the drug loading (p) of drugs (D) to antibody (Ab) is an integer from 1 to about 8.
2. The conjugate according to claim 1 , wherein the antibody is an intact antibody.
3. The conjugate according to claim 2 , wherein the antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO. 3 paired with a light chain having the amino acid sequence of SEQ ID NO. 4.
4. The conjugate according to claim 3 , wherein the antibody comprises two heavy chains having the amino acid sequence of SEQ ID NO. 3, each paired with a light chain having the amino acid sequence of SEQ ID NO. 4.
5. The conjugate according to claim 1 , wherein the antibody is humanised, deimmunised, or resurfaced.
6. The conjugate according to claim 1 , wherein p is 1, 2, 3, or 4.
7. The conjugate according to claim 6 , comprising a mixture of the antibody-drug conjugate compounds, wherein the average drug loading per antibody in the mixture of antibody-drug conjugate compounds 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 a cancer expressing CD22 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.