摘要:
Anti-Lewis Y antibodies are described. 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. Specifically, monomeric calicheamicin derivative/anti-Lewis Y antibody conjugates, compositions comprising the conjugates and uses of the conjugates are also described.
摘要:
The present invention provides processed for preparing a calicheamicin conjugate comprising removing glycosylation of a protein and reacting (i) an activated calicheamicin—hydrolyzable linker derivative and (ii) the deglycosylated protein. In one embodiment, the protein is an antibody, such as an anti-CD33 antibody (e.g., hp67.6), an anti-CD22 antibody (e.g., G544), an anti-Lewis Y antibody (e.g., G193), an anti-5T4 antibody (e.g., H8) or an anti-CD20 antibody (e.g., rituximab). In another embodiment, the calicheamicin derivative is an N-acyl derivative of calicheamicin or a disulfide analog of calicheamicin, such as N-acetyl gamma calicheamicin dimethyl hydrazide (N-acetyl calicheamicin DMH) and the hydrolyzable linker is 4-(4-acetylephenoxy) butanoic acid (AcBut) or (3-Acetylphenyl) acetic acid (AcPAc). Also provided are calicheamicin conjugates produced by such processes.
摘要:
Anti-Lewis Y antibodies are described. 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. Specifically, monomeric calicheamicin derivative/anti-Lewis Y antibody conjugates, compositions comprising the conjugates and uses of the conjugates are also described.
摘要:
A method is provided for preparing monomeric calicheamicin derivative/carrier conjugates with higher drug loading/yield and decreased aggregation. These conjugates are prepared by incubating a calicheamicin derivative and a proteinaceous carrier in a solution comprising a non-nucleophilic, protein-compatible, buffered solution, a cosolvent selected from the group consisting of propylene glycol, ethanol, DMSO, and combinations thereof, and an additive comprising at least one C.sub.6 -C.sub.18 carboxylic acid having a pH in the range from about 4.0 to 8.5 and at a temperature ranging from about 25.degree. C. to about 37.degree. C. for a period of time ranging from about 15 minutes to about 24 hours, and recovering monomeric calicheamicin derivative/carrier conjugates. Alternatively, the conjugates can be prepared by incubating the calicheamicin derivative and a proteinaceous carrier in a solution comprising a non-nucleophilic, protein-compatible, buffered solution and a cosolvent comprising t-butanol.
摘要:
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.
摘要:
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.