PYRROLOBENZODIAZEPINE-ANTI-HER2 ANTIBODY CONJUGATES
Conjugates of an antibody that binds to HER2 with PBD dimers.
1 .- 116 . (canceled)
117 . A conjugate of formula
where Ab is an antibody that binds to HER2, the antibody comprising a VH domain having the sequence according to SEQ ID NO. 1; and
wherein the drug loading (p) of drugs (D) to antibody (Ab) is an integer from 1 to about 8.
118 . The conjugate according to claim 117 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.
119 . The conjugate according to claim 117 wherein the antibody in an intact antibody.
120 . The conjugate according to claim 119 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.
121 . The conjugate according to claim 120 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.
122 . The conjugate according to claim 117 wherein the antibody is humanised, deimmunised or resurfaced.
123 . The conjugate according to claim 117 , wherein p is 1, 2, 3, or 4.
124 . The conjugate according to claim 123 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.
125 . The conjugate according to claim 117 , for use in therapy.
126 . The conjugate according to claim 117 , for use in the treatment of a proliferative disease in a subject.
127 . The conjugate according to claim 126 , wherein the disease is cancer.
128 . A pharmaceutical composition comprising the conjugate of claim 117 and a pharmaceutically acceptable diluent, carrier or excipient.
129 . The pharmaceutical composition of claim 128 further comprising a therapeutically effective amount of a chemotherapeutic agent.
130 . Use of a conjugate according to claim 117 in the preparation of a medicament for use in the treatment of a proliferative disease in a subject.
131 . A method of treating cancer comprising administering to a patient the pharmaceutical composition of claim 128 .
132 . The method of claim 131 wherein the patient is administered a chemotherapeutic agent, in combination with the conjugate.