ADC Conjugation Chemistry

With over a decade of extensive experience in antibody design and optimization to fit different bio-conjugation strategies, Creative Biolabs is dedicated to antibody-drug conjugation (ADC) discovery and development including ADC antibody screening, conjugation chemistry, linker and payload service, analytical characterization and validation, fill and finish and other antibody relevant services to deliver a promising ADC.

Background

For a complete ADC, antibody is the key component to determine the target specificity with the capability to deliver the cytotoxic payload (see Fig.1).

Structure and mechanism of action of ADC. Fig.1 Structure and mechanism of action of ADC. (Tsuchikama, 2018)

Via a wide range of conjugation chemistry, the payload drugs can be attached to various sites on an antibody. We offer various solutions for multiple potential conjugation sites of endogenous amino acids. In addition, we provide special moieties conjugation engineering services to achieve more precise site-directed conjugations and a narrower distribution of drug-to-antibody ratio (DAR). Antibodies conjugation can be generated by: (see Fig.2)

Fig.2 ADC generation by targeting natural amino acids. (Dennler, Eliane & Roger, 2015)1. Natural amino acids;
2. Interchain disulfides;
3. Engineered cysteines;
4. Non-natural amino acids;
5. Carbohydrate moiety;
6. N-terminus of heavy and light chain;
7. Engineered tags;
8. Strong protein-protein interaction such as Fc-binding domains which can be used to form non-covalent antibody conjugates;
9. Nucleotide binding site which is a valuable antibody modification site for photoaffinity labeling;
10. Antibodies with catalytic activity can be developed to form bioconjugates.

ADC Conjugation Chemistry Services

Creative Biolabs offers various ADC conjugation services to help you produce specific ADC to fit your program.

Creative Biolabs offers near-physiological conditions to perform ADC conjugation reactions to ensure antibody bioactivity. With senior scientists and technicians, we established several platforms including endogenous amino acids and other sites, especially lysine conjugation, cysteine conjugation and tyrosine conjugation.

ADC Design and Engineering Services

Creative Biolabs has explored and developed a series of methodologies about antibody design and engineering services to introduce various specific and chemically versatile conjugation sites into the sequence of antibody.

To avoid heavily dispersed drug-to-antibody ratio (DAR) caused by non-uniform distribution of the conjugation sites, Creative Biolabs provides a series of solutions to achieve a narrower DAR via ADC design and engineering services including:

Except for antibody engineering, Creative Biolabs also offers enzymatic or physical approaches to develop site-specific antibody-drug conjugation through modifying the carbohydrate moiety. Once engineered or natural antibodies are generated, they will be conjugated with payload with the help of linker/payload service. We will perform analytical characterization and validation for final produced ADC such as DAR, stability, conjugation site distribution, etc.

Hightlights

An appropriate conjugation design and chemistry is critically important for the success of an ADC product. With advanced antibody design platform and solutions, Creative Biolabs is dedicated to being your best companion in producing customized ADCs tailored to best fit your project. We are committed to maximizing your success. For more information or a detailed quote, please feel free to contact us.

References

  1. Tsuchikama, Kyoji, and Zhiqiang An. "Antibody-drug conjugates: recent advances in conjugation and linker chemistries." Protein & cell 9.1 (2018): 33-46.
  2. Dennler, Patrick, Eliane Fischer, and Roger Schibli. "Antibody conjugates: from heterogeneous populations to defined reagents." Antibodies 4.3 (2015): 197-224.

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