SAN DIEGO, Aug. 22, 2023 /PRNewswire/ — GemPharmatech is proud to announce the launch of NeoMab™, our independently developed fully antibody gene humanized mouse model, after four years of rigorous research and validation. NeoMab™ is specifically designed to meet the burgeoning therapeutic antibody development demands of biotechnology companies and pharmaceutical enterprises.
NeoMab™ is developed on the widely recognized BALB/c genetic background, rendering it highly suitable for industry-leading antibody discovery. This model retains the native mouse constant region encoding genes while incorporating human variable gene repertoires into endogenous loci (see Figure 1). This strategy gives rise to a formidable model that synergizes the strengths of the mouse immune system with human-specific variable regions, making it an ideal candidate for propelling antibody discovery and innovative research.
Through extensive in vitro and in vivo experimentation, the NeoMab™ mouse model has exhibited the following exceptional attributes:
Human-Like Variable Gene Usage Frequency: NeoMab™ mice employ human V(D)J genes to encode antibodies, mirroring gene usage frequency and sequence diversity remarkably similar to those observed in humans. Competent Immune System: NeoMab™ mice maintain an intact immune system, with proportions of diverse immune cell subsets akin to those found in BALB/c mice. Uninterrupted B-Cell Development: NeoMab™ mice demonstrate unimpeded antibody class switching, somatic hypermutation, and B-cell development. These mice showcase immunoglobulin levels in their serum comparable to those in BALB/c background mice. Robust Immune Response: After immunization with antigens, NeoMab™ mice exhibit antigen-specific serum titers similar to BALB/c mice.
The antibodies derived from the NeoMab™ mouse model offer the following advantages:
High Affinity: Antibodies obtained from NeoMab™ mice exhibit an affinity range of approximately 10-10 to 10-8 (as assessed by SPR detection), comparable to or even surpassing that of FDA-approved therapeutic antibody drugs. Effective In Vitro and In Vivo Functionality: The in vitro functional activity and in vivo efficacy of NeoMab™-derived antibodies closely mirror those observed in FDA-approved therapeutic antibody drugs. Reduced Risk of Immunogenicity: These antibodies are less likely to trigger immune responses, due to their higher success rate attributed to the human antibody gene background.
NeoMab™, a fully antibody gene humanized model from GemPharmatech, synergizes seamlessly with our advanced technical platform. It not only streamlines preclinical discovery and validation processes for forward-thinking pharmaceutical enterprises but also leverages licensing agreements and high-throughput screening platforms to expedite objectives efficiently and cost-effectively. This approach optimizes capital investment and galvanizes innovative drug development, ultimately paving the way for groundbreaking advancements in the field.
Comprehensive Support for Drug Development and Research
GemPharmatech’s commitment to advancing disease mechanism research, pharmaceutical development, and translational studies is exemplified through our array of model resources and support services. Our repository encompasses KOAP mice and tool mice tailored for drug screening, providing invaluable resources for target validation and pharmacological efficacy investigations. Additionally, our meticulously developed research service platforms span prominent domains such as oncology, metabolism, cardiovascular sciences, immunology, and neuroscience. By harnessing the synergy between these platforms and our model resources, we deliver comprehensive non-clinical research services across diverse fields.
NeoMab™, our fully antibody gene humanized model, stands as a pivotal addition within the GemPharmatech portfolio. This innovative platform seamlessly integrates with our expansive model resources and professional technical service platforms, elevating antibody research and discovery endeavors. Through this harmonious fusion, we empower drug development enterprises with comprehensive support, expediting the journey of uncovering and advancing new therapeutic agents. Our mission is to transform ideas into tangible solutions, foster collaborative partnerships, and achieve mutual success within the realm of scientific progress and enhanced healthcare outcomes.
Exploring the Fully Antibody Gene Humanized Model
The journey of therapeutic antibodies, since the pioneering approval of OKT3 in 1986 (Ecker, Jones et al., 2015), has witnessed rapid and transformative advancements, solidifying their status as a crucial facet of modern biopharmaceuticals. Despite this success, challenges persist, including low success rates, high costs, and extended timelines in antibody-based medication development. The issue of anti-drug antibodies (ADA) poses a significant concern, particularly for therapeutic antibodies which are classified as large-molecule drugs. Overcoming ADA formation risk in the preclinical stage remains a complex task.
In the pursuit of minimizing ADA, therapeutic antibodies have evolved through murine, chimeric, engineered, humanized, and fully human stages (Lu, Hwang, et al., 2020) (see Figure 2). Extensive research indicates that a higher proportion of human sequences within antibodies correlates with reduced ADA risk (Safdari, Farajnia et al., 2013). However, humanization entails additional costs and time, and even humanized antibodies cannot entirely eliminate ADA potential. For example, in the case of antibodies targeting PCSK9, the fully human antibodies Alirocumab and Evolocumab, derived from transgenic mice, have successfully obtained approval and been launched on the market. In contrast, Bococizumab failed to progress beyond phase III clinical trials due to its ADA (Ridker, Tardif et al., 2017). In comparison, fully human antibodies encoded exclusively by human sequences offer distinct advantages in development.
By 2022, over 160 antibody therapies had gained commercial approval, with a remarkable emphasis on fully human antibodies (Lyu, Zhao et al., 2022). Among the top 50 antibody drugs in terms of sales during that year, fully human antibodies accounted for 45%. Notably, 70% of approved fully human antibodies derived from transgenic mice, highlighting their efficacy and potential.
The first generation of fully antibody gene humanized models employed “TG+KO” technology, generating transgenic mice with human antibody gene segments while simultaneously knocking out the endogenous antibody genes. This led to platforms like HuMab (Lonberg, Taylor et al., 1994; Taylor, Carmack et al., 1994), established in 1994, and XenoMouse (Jakobovits, 1995), developed in 1997, which contributed significantly to approved 19 fully human antibodies. The subsequent generation utilizes site-specific knock-in techniques, introducing the human antibody variable region (V) gene library into the endogenous antibody gene locus of mouse while retaining the mouse constant region gene segments. One of the most renowned platforms in this field is Regeneron’s VelocImmune platform (Macdonald, Karow et al., 2014; Murphy, Macdonald et al., 2014), established in 2009, which has hitherto yielded seven approved antibodies. NeoMab™ adopts this strategy, overcomes the limitations associated with human gene segment numbers and preserves the regulation of endogenous expression and Fc-mediated signaling (Murphy, Macdonald et al., 2014), achieving an immune response closely resembling wild-type mice.
Contact us at [email protected] for further details on NeoMabTM Platform.
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