High-purity heterodimerization without purification complexity 

Generating correctly paired bispecific and multispecific antibodies (msAbs) at scale remains challenging. Traditional heterodimerization approaches either require extensive purification to remove mispaired species and homodimers or rely on mutations that compromise Fc stability and expression. Our proprietary Chain Exchange (ChEx) technology provides an efficient, data-driven solution for generating high-purity, correctly paired msAbs without purification bottlenecks.

The principle behind redox-driven heavy chain exchange  

ChEx uses controlled redox conditions to temporarily dissociate heavy chains while preserving heavy–light chain pairing. Engineered CH3 interface mutations then guide selective heterodimerization, allowing efficient recombination of heavy chain pairs. This elegant approach eliminates the need for complex purification while maintaining native-like Fc function and stability.

Schematic of the Chain Exchange (ChEx) process. Separate parental IgGs combine through a controlled redox step to form a defined heterodimer.

Proprietary mutations for selective pairing 

Our computationally designed mutation sets enable selective heterodimerization without compromising expression yields or biophysical properties. Structural validation is performed to confirm that mutations maintain wild-type-comparable Fc stability and domain interactions, ensuring that engineered constructs perform like native antibodies in therapeutic contexts. 

Analytical validation of dual-antigen engagement 

Comprehensive characterization by size-exclusion chromatography (SEC), ion exchange chromatography (IEX), LC-MS, and surface plasmon resonance (SPR) confirms that ChEx-generated heterodimers are single-species products with correct chain pairing and simultaneous dual-target binding. This analytical rigor ensures that products are suitable for therapeutic advancement without unexpected assembly variants. 

Results at a glance 

• Superior purity compared to alternative technologies: ChEx achieves high purity for correctly paired heterodimers, comparable to wild-type antibodies, and substantially higher than traditional approaches. 

• High-throughput format exploration enabled: A 12×12 antibody pairing matrix conventionally requires 144 individual transfections with subsequent purification. ChEx reduces this to 24 transfections with parallel generation of all combinations, enabling comprehensive format screening in weeks rather than months.  

• Confirmed dual-antigen binding: Comprehensive analytical characterization by methods such as SEC, IEX, and LC-MS confirms that ChEx products engage both target antigens simultaneously without assembly variants or off-target species. 

Accelerated development pathway 

Our high-throughput workflow allows generation and analytical characterization of diverse msAb architectures to identify the geometry that optimizes the identified therapeutic target, eliminating sequential iteration and format guessing.