Fully Human Antibody and TCR Mouse Models Showcase Biocytogen’s Capabilities to Innovate the Discovery of Novel Biologic Drugs
BEIJING–(BUSINESS WIRE)–#Antibody–Biocytogen Pharmaceuticals (Beijing) Co., Ltd. (“Biocytogen”, HKEX: 02315) officially announces the RenMice® series, which includes a collection of independently developed, fully human antibody mice and TCR mice with proprietary intellectual property. The term “Ren”, defined as “human”, is derived from the Chinese pinyin for “人” (rén), which integrates Eastern cultural elements and represents Biocytogen’s commitment to developing innovative technologies that advance the discovery, development and delivery of novel therapeutics, ultimately benefiting human health. The RenMice® series encompasses five strains of fully human antibody/TCR mice: RenMab™, RenLite®, RenNano®, RenTCR™, and RenTCR-mimic™. These mice provide robust support for the discovery of fully human monoclonal antibodies, bispecific antibodies, bispecific antibody-drug conjugates (BsADCs), nanobodies, fully human T-cell receptors (TCRs), and TCR-mimic antibodies. Biocytogen is also generating more strains of fully human RenMice for MHC cluster genes, NK cell cluster genes, and other gene clusters for diverse drug development purposes, which will be integrated into the RenMice portfolio upon successful development.
Since their successive release in 2019, Biocytogen’s RenMice series has received global recognition in the biopharmaceutical and biotechnology field. As of June 30, 2023, Biocytogen has entered into RenMice licensing agreements with 20 biopharmaceutical/biotechnology companies worldwide; 42 target-nominated antibody development projects have been initiated. Additionally, 50 antibody drug co-development/out-licensing/transfer agreements have been established with partners worldwide. As Biocytogen’s Project Integrum has completed 900+ target-specific antibody discovery projects and identified 400,000-500,000 antibody molecules, the number of external therapeutic antibody co-development/out-licensing/transfer agreements are expected to increase significantly. The successful development of new RenMice platforms will further enhance Biocytogen’s technical capabilities in novel drug discovery and accelerate the development of new therapeutics in collaboration with global partners.
RenMab Mice: A Leading Model for Fully Human Monoclonal Antibody Discovery
Biocytogen developed RenMab mice using its proprietary Size-Unlimited Precise Chromosome Engineering (SUPCE) technology, which allowed for replacement of the murine antibody heavy and light chain variable region genes with the corresponding human counterparts in situ. Thus, RenMab is one of the few mouse models available that has the complete repertoire of human antibody variable region genes. Following immunization, RenMab mice generate diverse fully human monoclonal antibody sequences targeting various epitopes with affinity similar to wild-type mice. Importantly, these antibodies possess excellent specificity and physicochemical properties and do not require additional in vitro humanization, leading to substantial time and cost savings in downstream development, and an elevated likelihood of successful clinical translation. As a fully human antibody mouse model developed independently in China, RenMab received Chinese patent authorization in 2023.
RenLite Mice: A Common Light Chain Model for the Discovery of Fully Human Bispecific Antibodies and Bispecific ADCs
Similar to RenMab mice, RenLite mice feature the complete in situ replacement of human antibody heavy chain variable region genes. Unlike RenMab mice, RenLite mice possess a single human antibody light chain variable region gene. As a result, antibodies generated by RenLite mice share a common light chain, effectively reducing heavy and light chain mismatching when assembled into bispecific antibodies (BsAbs). By incorporating Knobs-into-Holes (KIH) technology, the mismatch rate of heavy-heavy chain is also significantly reduced, collectively resulting in an assembly success rate of over 95%, significantly reducing the complexity of the CMC process. BsAbs assembled from RenLite-derived antibodies resemble monoclonal antibodies and exhibit favorable physicochemical properties, and can be further developed into bispecific ADCs.
RenNano Mice: A Fully Human Heavy Chain-Only Model for Nanobody Discovery
RenNano mice were developed via genetic modification of the antibody constant region in RenMab mice. Following immunization, RenNano mice produce fully human heavy-chain-only antibodies (HCAbs) that can bind to antigens without a light chain. RenNano-derived HCAbs possess diverse CDR3 sequences and can recognize a variety of epitopes with excellent specificity and affinity. HCAbs derived from RenNano mice demonstrate robust biological function both in vitro and in vivo, making them suitable for various drug modalities, including bispecific antibodies, multispecific antibodies, and cell therapies. Using RenNano mice, Biocytogen initiated the “Nano 100 Project” in February 2023 to discover fully human therapeutic nanobodies against over 100 different targets.
RenTCR Mice: A Novel Fully Human TCR Discovery Platform
Developed using SUPCE technology, RenTCR mice can directly produce fully human TCR sequences after immunization. These mice lack tolerance to foreign antigens, such as those from humans or viruses, enabling the generation of high-affinity TCRs targeting human TAAs and viral antigens. These TCRs use human genes to avoid immunogenicity concerns. Furthermore, they do not require further mutagenesis to improve binding affinity, reducing the risk of introducing off-target toxicity. Using RenTCR mice for human TCR discovery does not require patient samples, unlike traditional tumor-infiltrating lymphocyte (TIL) therapy, and can generate a more diverse range of TCR sequences than TILs. The successful launch of RenTCR mice will accelerate collaborations with research institutions focused on therapeutic TCR molecules, including TCR-T cell therapy companies.
RenTCR-mimic Mice: Models for Fully Human TCR-mimic Antibody Discovery
RenTCR-mimic mice were developed via humanization of class I MHC molecules in RenMab and RenLite mice. Immunization of RenTCR-mimic mice with pHLA complexes yields TCR-mimic antibodies that specifically target pHLA without recognizing human HLA molecules. Unlike traditional antibodies that can only recognize cell surface or extracellular antigens, antibodies generated by RenTCR-mimic mice can target intracellular antigens by recognizing pMHC complex on the cell surface, significantly expanding the range of druggable targets. Combined with its high-throughput antibody screening platform, Biocytogen can rapidly identify highly specific and high-affinity TCR-mimic antibodies, overcoming limitations associated with low affinity and tumor immune escape caused by endogenous TCRs. Fully human TCR-mimic antibody sequences can be used in the development of T-cell engagers and CAR-T therapies. Currently, TCR-mimic antibodies against over 10 intracellular TAAs, CTAs, mutated antigens, and viral antigens have been developed.
RenMice KO Mice: Specialized Discovery for Challenging Targets and Project Integrum
Due to the presence of immune tolerance, it is difficult to use conventional mouse immunization methods to generate antibodies targeting antigens with high homology between human and mouse. Knocking out the target gene in RenMice can reduce immune tolerance to the antigen, making it possible to obtain high-affinity, highly specific fully human antibodies against both homologous and heterologous regions following immunization. This strategy can increase antibody diversity against challenging targets like GPCRs and highly homologous targets, thereby improving screening success rates. It also increases the chances of obtaining species cross-reactive antibodies, facilitating downstream multi-species in vivo efficacy and safety evaluation. Over the past three years, Biocytogen’s Project Integrum has been utilizing RenMice KO mice to develop fully human antibody drugs against over 1,000 different targets. This initiative has yielded numerous fully human antibodies capable of cross-species recognition and established an antibody library consisting of 400,000 to 500,000 antibody sequences, which can ultimately help partners significantly improve project predictability, reduce development time and cost, and increase the success rate of drug development.
Biocytogen (HKEX: 02315) is a global biotechnology company that drives the research and development of novel antibody-based drugs with innovative technologies. Using its proprietary RenMab™/RenLite®/RenNano® mice platforms for fully human monoclonal, bispecific/multispecific antibody and nanobody development, Biocytogen has integrated its in vivo drug efficacy screening platforms and strong clinical development expertise to streamline the entire drug development process. Biocytogen is undertaking a large-scale project to develop first-in-class and/or best-in-class antibody drugs for more than 1000 targets, known as Project Integrum (RenMice® HiTS Platform). As of June 30, 2023, 50 therapeutic antibody co-development/out-licensing/transfer agreements and 42 target-nominated RenMice® licensing projects have been established worldwide, including several partnerships with multinational pharmaceutical companies (MNCs). Biocytogen’s pipeline is comprised of 10 core assets, with partnerships established for multiple clinical assets. Headquartered in Beijing, Biocytogen has branches in China (Haimen Jiangsu, Shanghai), USA (Boston, San Francisco), and Germany (Heidelberg). For more information, please visit http://en.biocytogen.com.cn.
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