Compositions comprising antibody-duocarmycin drug conjugates
Inventors
Osinga, Niels Jaap • VAN BOCKXMEER, Ernst Johannes Bernardus
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11077204-B2
Publication Date
2021-08-03
Expiration Date
Abstract
The present invention relates to lyophilized compositions comprising antibody-duocarmycin drug conjugates.
Core Innovation
The invention relates to lyophilized pharmaceutical compositions that include an antibody-drug conjugate of formula (I), a buffering agent, a lyoprotectant, and a surfactant, with a defined molar ratio of lyoprotectant to antibody-drug conjugate of 1,400-3,200 to 1. In the composition, the monoclonal antibody (mAb) is included as part of the antibody-drug conjugate. The described compositions are further characterized as buffered, lyophilized systems intended to maintain the properties of the antibody-drug conjugate during drying.
A key part of the disclosed formulation system is the selection of a buffered lyoprotectant and a nonionic surfactant system in combination with cysteine-linked ADCs derived from duocarmycin. The disclosed lyoprotectants include trehalose and sucrose, including other saccharides, and the nonionic surfactant is exemplified by polysorbate 20, with other surfactants also referenced. The antibody-drug conjugates are described with average DAR in the range of 2-3, preferably 2.6-2.9, and an example ADC includes SYD985/trastuzumab vc-seco-DUBA (formula II).
The disclosure also relates to freeze-drying constraints tied to product behavior, including relationships involving collapse temperature and glass transition temperature (Tg) under sub-atmospheric pressure conditions. An optional annealing step is described to reduce lyophilization time and improve lyophilized cake porosity and appearance. The examples report effects of changing trehalose:ADC molar ratio on lyophilized cake quality and on stability in solution, including monomer versus high molecular weight (HMW) changes and solution aggregation or sub-visible particulates.
Claims Coverage
The independent claims cover two composition formats for an antibody-drug conjugate of formula (I) with a buffering agent, a lyoprotectant, and a surfactant, defining a lyoprotectant-to-antibody-drug-conjugate molar ratio of 1,400-3,200 to 1. The inventive features center on the specified excipient system and molar ratio, with further claim limitations addressing formulation options and freeze-drying temperature relationships.
Lyophilized antibody-drug conjugate composition with defined lyoprotectant-to-ADC molar ratio
A lyophilized composition comprising an antibody-drug conjugate of formula (I), a buffering agent, a lyoprotectant, and a surfactant wherein the molar ratio of lyoprotectant to antibody-drug conjugate is 1,400-3,200 to 1, wherein mAb is a monoclonal antibody.
Buffered antibody-drug conjugate composition with water and defined lyoprotectant-to-ADC molar ratio
A composition comprising an antibody-drug conjugate of formula (I), a buffering agent, a lyoprotectant, a surfactant, and water, wherein the molar ratio of lyoprotectant to antibody-drug conjugate is 1,400-3,200 to 1, wherein mAb is a monoclonal antibody.
Overall, the claim coverage is centered on lyophilized and buffered aqueous antibody-drug conjugate compositions that include a buffering agent, a lyoprotectant, and a surfactant with a specified lyoprotectant-to-antibody-drug-conjugate molar ratio of 1,400-3,200 to 1. Dependent claims further specify particular excipient selections, narrower sub-ranges for the molar ratio, and additional formulation/process constraints including freeze-drying temperature relationships and an optional annealing step.
Stated Advantages
Improves lyophilized cake porosity and appearance.
Reduces lyophilization time.
Improves stability in solution, including reduced aggregation/particulates and controlled monomer/HMW changes.
Documented Applications
Not explicitly described in patent.
Interested in licensing this patent?