Patent ID: 9352050
Filing Date: 2016-05-31
CPC Classification: A61K,A61P,C07D

Claim Text:
1. A process for preparing a compound according to formula 5a comprising (i) reacting 9a and 11 together in the presence of 1-propanephosphonic acid anhydride (T3P) to create compound 13a (ii) catalytic hydrogenation with Pd/C of compound 13a in a THF:H (iii) combining a solution of 14a in THF with a compound according to formula 15 in a reaction substantially free of base to produce compound 6a (iv) reacting a compound according to the formula 6a with a compound according to formula 19a in THF in the presence of DCC to produce compound 20a (v) combining 20a with a ε-amino containing peptide 2 dissolved in an aprotic polar (vi) dissolving compound 3a in DMSO; (vii) adding histidine buffer at pH between about 5.5 to about 7.5 to the solution of DMSO and 3a of step (vi); (viii) Adding an antibody comprising a variable light region comprising SEQ ID NO:5 and a variable heavy region comprising SEQ ID NO:6 to the solution of step (vii), so as to have a peptide:antibody molar ratio of between about 1.8:1 to about 3:1; (ix) Agitating the mixture formed in step (viii) at a medium speed so as to avoid foaming the reaction mixture for at least about 1 hr at between about pH 5.5 and about pH7.5 and at a temperature of between about 5° C. and 35° C.; and (x) Filtration of the solution from (ix) to extract the resultant peptide-linker antibody conjugate 5a wherein q=1, 2, 3, 4, or 5, X=F or Cl, and m=3, 4, or 5.