Carbohydrate-Based Method for Generating Site-Specific Antibody-Drug Conjugates
- *Abstract
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Application
- Linking drugs to antibodies for targeteddisease treatment, such as cancer
- Selectively linking flurophores, DNA, proteinor any other desirable biochemical compound to antibodies for diagnostic,therapeutic, or research purposes
ProblemsAddressed
- Conjugation is not limited to antibodies
- Natural method of conjugation; carbohydratescan be added to antibodies either in vitro or in vivo
- Conjugation chemistry does not require a toxicmetal catalyst for antibody conjugation, thereby lessening safety concerns
- Conjugation occurs at well-defined positionsand does not impact antibody specificity or stability
- Methods used to produce the ADCs are moreattractive than conventionally used electrophilic conjugation methods for ADCpreparation
TechnologySummary
The use of antibody drug conjugates (ADCs) is attractive asan anti-cancer therapeutic. Antibodiesthat recognize oncogenic cells are conjugated to cytotoxic drugs and used amechanism to selectively destroy cancer cells. The typical conjugation chemistry often involves the use of toxic metalcompounds, which must be removed from solution before the antibodies can beused as a therapeutic. Additionally,many ADCs are made using methods that yield unpredictable heterogeneousmixtures of conjugates, some of which cause a decreased antibody stability orspecificity.
The technology presented is a next-generation antibody drugconjugate. The unique benefit of thistechnology is that the antibody is modified with a carbohydrate at a preciselocation and naturally attached through post-translational modification of theantibody heavy chain. A simpleincubation with a glycosyl-transferase followed a metal-free click chemistryallows predictable, controllable, and reproducible conjugation of biochemicalcompounds. This carbohydrate conjugationmethod has the ability to not only link to drugs, but easily link othercompounds such as: fluorophores, DNA, protein, or any other desirablebiochemical compound to the antibody.
Inventors
• Geert-JanBoons, Distinguished Professor in Biochemical Sciences
• JasonWang
Theresearch of the Boons Group deals with the synthesis and biological functionsof carbohydrates and glycocongugates. The diversity of topics to which thegroup has significantly contributed include the development of new and bettermethods for synthesizing exceptionally complex molecules, the use of newmethods in the synthesis and study of properties of complex carbohydrates ofincreasing size and complexity, the development of synthetic cancer andbacterial vaccines, the design and synthesis of glycosidase inhibitors and theuse of synthetic compounds for the study of innate immunity
https://www.ccrc.uga.edu/~gjboons/boons/Home.htm
TechnologyDevelopment and IP Status
· Pre-clinical research stage
· PCT publication WO 2015/024969
- 國家/地區
- 美國
