As an undoubted pioneer in the bispecific antibody (BsAbs) development and manufacture, Creative Biolabs offers many different formats of BsAbs. Based on our vast experience gained from developing hundreds of antibodies, we can offer IgG(L,H)-Fv BsAbs with high affinity and low immunogenicity for both academic and clinical purposes.
The production of bispecific IgG molecules is difficult, because the antigen-binding sites are built by the variable domains of the light and heavy chain (VL, VH). A BsAb needs two different heavy chains and two different light chains, and displays asymmetry on account of the presence of, at least, two different Fv regions. Promiscuous pairing of heavy and light chains of two antibodies produced in one cell are able to theoretically lead to 10 different molecules, among which just one being bispecific and the remaining pairings forming non-functional or monospecific molecules. To direct and to drive correct assembly of correct binding sites, such as heavy and light chains, is one of the challenges of producing BsAb, and a variety of approaches have been development over the past years to solve this problem.
Figure 1. Diagram of IgG(L,H)-Fv BsAb. (Spiess, C., 2015)
IgG(L,H)-Fv BsAbs, one kind of BsAbs with the improved feature and promising therapeutic potential, are constructed by appending VH and VL domains to the C-terminal of two distinct heavy chains. It is essentially a full-length antibody with an additional C-terminal Fv region. The engineered C-terminal Fv is monovalent while the two identical N-terminal Fv regions are those of a typical full-length IgG which provide bivalent antigen binding activity. The C-terminal VH/VL pairing may further contribute to the hetero-specificity of the heavy chains, which enables the IgG(L,H)-Fv to co-engage distinctly target antigens with different valencies simultaneously.
Applications of BsAbs cover an extensive spectrum which contains diagnosis, imaging, prophylaxis and therapy. A great number of genetically engineered BsAbs are now in clinical research, some in advanced stages and some already available as drugs. These BsAbs exhibit quite different formats, with some being large and comprising constant regions and some of small size without constant regions. In practice, a majority of main format clusters are represented in one or more molecules which have advanced into the clinic.
With the well-established IgG(L,H)-Fv BsAb generation platform, the experienced scientists here at Creative Biolabs are dedicated to help you develop unique scFv1-PEG-scFv2 BsAb. We also provide other various services regarding BsAbs development. Please feel free to contact us for more information and a detailed quote.
1. Spiess, C.; et al. Alternative molecular formats and therapeutic applications for bispecific antibodies. Molecular immunology. 2015, 67(2): 95-106.
2. Brinkmann, U.; Kontermann R. E. The making of bispecific antibodies. MAbs, 2017, 9(2): 182-212.