bYlok® technology is changing the way bispecific antibodies are designed. Achieving the correct heterodimerization of light and heavy chains during bispecific production can be challenging, and it can be difficult to remove such unwanted mispaired species as their structure is similar to the correctly paired, desired format. Whilst the knobs-into-holes technology solves heavy chain mispairing, bYlok® technology offers an easy to implement solution to address heavy chain-light chain (HC-LC) mispairing.
The bYlok® technology is an elegant modification to the natural antibody design, and has no observed negative impact on molecule stability or in silico predicted immunogenicity*. Furthermore, bYlok® bispecifics can be purified using standard downstream processes used for traditional monoclonal antibodies, alleviating the need to spend time developing new platform processes.
How it works
To solve HC-LC mispairing, the bYlok® technology involves the engineering of the native disulphide bridge, moving it from the constant domains (CH1/CL) to the variable domains (VH/VL). This modification favours the formation of correct HC-LC heterodimers and delivers >95% correct chain pairing*.
Plug and play with Lonza in Your Lab®
The bYlok® technology is readily accessible for use in your own lab, in true plug-and play format, unlocking new possibilities for discovery phase customers, from small biotech to big pharma. The technology can be easily implemented to build and retrofit bispecific antibodies through a research license from Lonza.
Read about how one of our customers has used bYlok® to develop an improved version of their bispecific antibody (CDX) ‘for the treatment of relapsed/refractory acute myeloid leukaemia (AML), a subset of acute lymphoblastic leukaemia (ALL), and potentially for conditioning in bone marrow transplantations, which has demonstrated significantly enhanced efficacy in in vitro testing. Additional in vivo studies are currently underway’ – Hemogenyx Pharmaceuticals plc.
Read the Hemogenyx development update
*Lonza internal data