Calicheamicin derivative-carrier conjugates
Methods for preparing monomeric cytotoxic drug/carrier conjugates with a drug loading significantly higher than in previously reported procedures and with decreased aggregation and low conjugate fraction (LCF) are described. Cytotoxic drug derivative/antibody conjugates, compositions comprising the conjugates and uses of the conjugates are also described. Monomeric calicheamicin derivative/anti-CD22 antibody conjugates, compositions comprising the conjugates and uses of the conjugates are also described.
1. A composition comprising a drug conjugate, wherein said drug conjugate comprises calicheamicin derivatives and an antibody and has the formula:
wherein the antibody comprises SEQ ID NO: 1 for CDR-H1, residues 50-66 of SEQ ID NO: 27 for CDR-H2, SEQ ID NO: 3 for CDR-H3, SEQ ID NO: 4 for CDR-L1, SEQ ID NO: 5 for CDR-L2 and SEQ ID NO: 6 for CDR-L3;
wherein n is 3 to 9; and
wherein the composition is less than 10% by weight of unconjugated antibody.
2. The composition of claim 1 , wherein the antibody comprises a light chain variable region as set forth in SEQ ID NO: 19 and a heavy chain variable region as set forth in SEQ ID NO: 27.
3. The composition of claim 1 , wherein the antibody comprises a light chain consisting of residues 21 to 239 of SEQ ID NO: 28 and a heavy chain consisting of residues 20 to 466 of SEQ ID NO: 30, and wherein the antibody is expressed in a mammalian cell.
4. The composition of claim 1 , wherein the antibody comprises a light chain consisting of an amino acid sequence resulting from the expression of SEQ ID NO: 29 in a mammalian cell and a heavy chain consisting of an amino acid sequence resulting from the expression of SEQ ID NO: 31 in a mammalian cell.
5. A pharmaceutical composition comprising the composition of claim 1 and a pharmaceutically acceptable excipient, diluent or carrier.