Combination of antibody-drug conjugate with parp inhibitor
A technology of conjugates and inhibitors, applied in the field of pharmaceutical compositions
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Embodiment 1
[0654] Example 1: Generation of Anti-HER2 Antibody-Drug Conjugate (1)
[0655] According to the production method described in International Publication No. WO 2015 / 115091 and using an anti-HER2 antibody (antibody comprising a heavy chain and a light chain, the heavy chain consisting of amino acid residues 1 to 449 of SEQ ID NO: 1 , and the light chain consists of the amino acid sequence consisting of amino acid residues 1 to 214 of SEQ ID NO: 2), resulting in an anti-HER2 antibody-drug conjugate, wherein the drug-linker represented by the following formula is via a thioether bond Conjugated with anti-HER2 antibody (hereinafter referred to as "HER2-ADC (1)"):
[0656] [Formula 23]
[0657]
[0658] Where A represents the linking position with the antibody. The DAR of HER2-ADC (1) was 7.7 or 7.8.
Embodiment 2
[0659] Example 2: Generation of Anti-TROP2 Antibody-Drug Conjugate (1)
[0660] According to the production method described in International Publication No. WO 2015 / 098099 and International Publication No. 2017 / 002776 and using an anti-TROP2 antibody (an antibody comprising a heavy chain and a light chain consisting of amino acid residues of SEQ ID NO: 5 5 to 470, and the light chain consists of the amino acid sequence consisting of amino acid residues 21 to 234 of SEQ ID NO:6), resulting in an anti-TROP2 antibody-drug conjugate, wherein represented by The drug-linker was conjugated to the anti-TROP2 antibody via a thioether bond (hereinafter referred to as "TROP2-ADC (1)"):
[0661] [Formula 24]
[0662]
[0663] Where A represents the linking position with the antibody. The DAR of TROP2-ADC (1) was 3.5 to 4.5.
Embodiment 3
[0664] Embodiment 3: the generation of compound (1)
[0665] According to the production methods described in International Publication No. WO 2014 / 057687 and International Publication No. 2015 / 115091, a compound represented by the following formula (hereinafter referred to as "compound (1)") was produced:
[0666] [Formula 25]
[0667] .
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