ADC Conjugation Chemistry Service

Background

Featured Services ADC Conjugation Methods ADC Design and Engineering Services

Highlights FAQs Resources Related Sections

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, the antibody is the key component to determine the target specificity with the capability to deliver the cytotoxic payload (see Fig.1). 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). As depicted in Fig.2, antibody conjugation can be generated by:

Natural amino acids;
Interchain disulfides;
Engineered cysteines;
Non-natural amino acids;
Carbohydrate moiety;
N-terminus of heavy and light chain;
Engineered tags;
Strong protein-protein interaction such as Fc-binding domains which can be used to form non-covalent antibody conjugates;
Nucleotide binding site which is a valuable antibody modification site for photoaffinity labeling;
Antibodies with catalytic activity can be developed to form bioconjugates.

Fig.1 Structure and Mechanism of Action of ADC.^1,3

Fig.2 ADC Generation by Targeting Natural Amino Acids.^2,3

What We Provide

ADC Conjugation Methods

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.

Method	Advantages	Disadvantages	Applications
Lysine Conjugation	High payload loading	Heterogeneous DAR	Broad applicability
Cysteine Conjugation	Stable and site-specific	Requires reduction	Homogeneous ADCs
Tyrosine Conjugation	Minimal off-target modifications	Limited tyrosine residues	Specialized designs
Enzymatic Conjugation	Exceptional precision	Enzyme-substrate dependency	Homogeneous, advanced ADCs

ADC Design and Engineering Services

Creative Biolabs offers advanced methodologies for antibody design and engineering, enabling the introduction of precise and chemically versatile conjugation sites to optimize antibody-drug conjugates (ADCs). To achieve a consistent and narrower drug-to-antibody ratio (DAR), our solutions include:

Thiol Engineered Antibodies

Enhancing conjugation efficiency by engineering thiol groups at targeted sites.

Unnatural Amino Acids

Genetic incorporation of residues like p-Acetyl Phenylalanine for site-specific conjugation.

Enzyme-Mediated Modifications

Utilizing enzymes such as sortase A, transglutaminases, and formylglycine-generating enzymes for precise site modifications.

Meditope-Based Conjugations

Creating specific binding cavities to enable controlled payload attachment.

Intein-Fusion Antibodies

Facilitating modular and seamless payload conjugation through intein-based engineering.

N-Glycan Engineering

Modifying glycan moieties for site-directed drug attachment.

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.

Why Choose Us?

With expertise and dedication;
Advanced antibody design platform;
Comprehensive conjugation capabilities.

An appropriate conjugation design and chemistry is critically important for the success of an ADC product. With advanced antibody design platforms 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.

FAQs

What is DAR, and why is it important?

DAR (drug-to-antibody ratio) determines the number of payload molecules attached to each antibody. An optimized DAR ensures balanced efficacy and safety, reducing toxicity and maximizing therapeutic windows.

How does Creative Biolabs ensure site-specific conjugation?

Our advanced methodologies, including enzymatic conjugations and engineered antibodies, precisely target desired conjugation sites, minimizing off-target modifications.

What analytical methods are employed to validate ADC quality?

We use techniques like HPLC, mass spectrometry, and stability testing to validate DAR, payload distribution, and ADC integrity.

How is ADC stability ensured during the fill and finish process?

Our fill and finish services employ cryoprotectants and rigorous storage protocols to preserve ADC stability.

References

Tsuchikama, Kyoji, and Zhiqiang An. "Antibody-drug conjugates: recent advances in conjugation and linker chemistries." Protein & cell 9.1 (2018): 33-46.
Dennler, Patrick, Eliane Fischer, and Roger Schibli. "Antibody conjugates: from heterogeneous populations to defined reagents." Antibodies 4.3 (2015): 197-224.
Distributed under Open Access license CC BY 4.0, without modification.