Creative Biolabs is an undisputed global leader in the rapidly emerging market of bispecific antibodies (BsAbs). Based on the rich experiences and advanced technology, we offer a variety of formats of BsAbs, including bispecific SEEDbodies with a strand-exchange engineered domains (SEED) CH3 heterodimers.
BsAbs provide novel opportunities to intervene in disease mechanisms and offer important advances in therapeutics. There are several methods to generate BsAbs, such as chemical crosslinking, tandem fusions of scFv or V domain antibodies, as well as their fusion to the C- or N-terminus of heavy chains. BsAbs have been produced in hybrid hybridomas, however, due to the complexity of species produced in cell culture, it is difficult and expensive to purify. There remains a requirement for engineered bispecifics with potent properties that enable to be readily formed in high yield from mammalian cell culture.
Creative Biolabs has utilized a heterodimeric Fc platform which allows the design of bispecific and asymmetric fusion proteins through devising SEED CH3 heterodimers. These derivatives of human IgG and IgA CH3 domains form complementary human SEED CH3 heterodimers. These heterodimers are made up of alternating segments of human IgA and IgG CH3 sequences. The generated pair of SEED CH3 domains preferentially combines to produce heterodimers when expressed in mammalian cells. SEEDbodies are fusion proteins with SEED CH3 heterodimers in a Fc analogue platform for asymmetric binders or immunofusions and BsAbs. SEEDbodies are made up of [IgG1 hinge]-CH2-[SEED CH3] and are able to be genetically linked to one or more fusion partners.
Figure 1. This figure shows the all CH3 and SEED domains, and the AG.GA heterodimer. The complementary AG and GA SEED CH3 domains are drawn beneath their parent IgG and IgA-derived CH3 domains, with a common axis of symmetry to emphasize their identical crossover segments. (Davis, J. H., 2010)
SEEDbody Fc architecture offers prior heterodimer generation and retention of crucial Fc properties. In this way, it enables a rapid first purification step with rpA, and combination of the SEEDbody Fc analogue to other proteins of interest. Thus, the problem of half-life extension can be solved, which is intrinsic to the use of small single scaffold binding proteins, engineered forms of the intact antibody combining site such as the scFv, or V domain binders. The mono-Fab- SEEDbody protein lends itself to formation of a bispecific by fusing a scFv to the N-terminus of the single truncated SEEDbody chain, to create a bispecific SEEDbody which averts the complications of generating mixtures of L chains in mammalian cell expression. In addition, the symmetric fusion of distinct scFv antibody binding sites or single domain binders to each of the SEEDbody Fc analogue chains is a potential and powerful approach for engineering bispecific SEEDbodies.
With the well-established bispecific SEEDbody generation platform, the experienced scientists here at Creative Biolabs are dedicated to helping you develop therapeutic BsAbs. We also provide other various services regarding BsAbs development. Please feel free to contact us for more information and a detailed quote.
Davis, J. H.; et al. SEEDbodies: fusion proteins based on strand-exchange engineered domain (SEED) CH3 heterodimers in an Fc analogue platform for asymmetric binders or immunofusions and bispecific antibodies. Protein Engineering Design and Selection. 2010, 23(4): 195-202.