Mouse mAbs Development

Overview

Our team has decades of experience on high quality monoclonal antibody development services. DIMA’s mAb development platform is a revolutionary technology platform for monoclonal antibody development. Different from hybridoma fusion platform, we can directly isolate IgG genes from B cells of immunized animals. At present, we have successfully completed a number of custom development projects with high satisfaction (Please see our customer testimonials).

Advantages

Mouse is the best animal model system to study human diseases. Before clinical trial, mouse disease model is commonly used to simulate the pathogenesis of human diseases and test the drug responses. Till today, more than 90% of the therapeutic antibody drugs were developed from mouse or humanized mouse. There are well-established systems to humanize mouse monoclonal antibodies. Therefore, mouse is still the first choice when coming for a therapeutic antibody drug developmental program.

Although mouse hybridoma technology was developed several decades ago, it is still the major working horse people commonly using for monoclonal antibody development. However, there are limitations in the preparation of monoclonal antibodies by traditional hybridoma methods, such as low fusion efficiency of hybridoma, long preparation process, unstable hybridoma cells, etc. DIMA’s mAbs technology platform for mouse monoclonal antibody development is a total revolution, which has a number of advantages.

Service Consultation

     

    Mouse DIMA mAbsHybridoma mouse monoclonal antibody
    Short development process (4-5 months)Long development process (8-10 months)
    High project success rate（80-90%）Low project success rate（50%）
    High cloning efficiency (thousands of clones from one immunized animal)Low cloning efficiency
    Direct acquisition of antibody IgG gene sequence, easy to maintain and transmit informationHigh cost of hybridoma cell preservation, Need separate cloning step to clone IgG gene
    High quality consistency between batches, and possible to automate the processHybridoma cells are unstable and might loss during passage
    No need to kill animals (PBMCs are good enough)Animals need to be killed to separate the splenocytes

    Application Scenario

    Therapeutic antibody drug development
    Since the first mouse monoclonal antibody drug muromonab OKT3 was developed in 1986, now close to 100 monoclonal antibody drugs have been approved by FDA and it is a multi-hundred billion dollars market. Monoclonal antibodies have been used to treat different diseases, including cancer, infectious diseases, immunological disorders, etc. Many therapeutic antibody drugs become multi-billion dollar blockbuster, such as Humira (anti-tumor necrosis factor (TNF), Keytruda (anti-Pd-1), Praluent (anti-PCSK9), etc. In the future, the research and development trend of mouse monoclonal antibody will focus on new targets, new indications, new combinatorial treatment and so on.

    The top 5 therapeutic antibody drugs in global sales by 2018 (Source: Genetic Engineering and Biotechnology News 2019-03-11)

    RankDrug name (trade name)CompanyBillion dollars
    1HumiraAbbVie19.9
    2OpdivoBMS7.6
    3KeytrudaMerck7.2
    4HerceptinRoche7.0
    5AvastinRoche6.8

    Major diseases treated by antibody drugs

    DiseasesMechanism/targetRepresentative drugs
    Cancerblocking ligand bindingcetuximab
    CDC EffectRituximab
    ACDC EffectTrastuzumab
    Block cell signalPertuzumab
    Inhibition of angiogenesisBevacizumab
    ImmunosuppressantPD-1/L1 Monoclonal Antibody
    OtherBasiliximab, etc
    Immunological DisordersReceptor blocking and regulationOmalizumab
    Block cytokinesAdalimumab
    Depletion antigen producing cellRituximab

    Application in clinical diagnosis
    Since the approval of Herceptin and HER2 IHC detection reagents by FDA in 1998, mouse monoclonal antibodies have played an important role in clinical diagnosis. As of 2018, FDA has approved 35 companion diagnostic products and quite a number of immunological assaysuse mouse monoclonal antibodies. In addition, mouse monoclonal antibodies have also been widely used in the field of in vitro diagnosis.

    Application in scientific research
    In the past 30 years, mouse monoclonal antibodies have played an important role in scientific research and are the basic reagents for a lot of immunological assays.

    Comparisonsbetween rabbit monoclonal antibody and mouse monoclonal antibody

    Comparison itemsRabbit monoclonal antibodyMouse monoclonal antibody
    Affinity+++++++
    New IHC clones++++++++
    Oldand Common IHC clones+++++++
    Maturity for antibody drug development+++++++
    Common IVD clones++++++

    Service details

    Custom mouse mAbs development procedure&deliverables

    StepService detailsDeliverablesEstimated production cycle (week)
    Immunogen preparationPlasmid construction, mammalian cell produced immunogens or supplied by customer7-10 weeks
    Animal immunizationImmunize two animals (mice) against the same antigenCrude sera and ELISA data on anti-serum titer test8-12 weeks
    Collect mouse splenocytesDissect animal and cryopreservation; target positive B cell enrichment and single B cell expansion100ul B cell supernatant;B cell supernatant ELISA test data4 weeks
    DIMA mAbs cDNA cloning, sequencing and storageIgG gene cloning, Expression vector construction; small-scale antibody production and validation; select 1-2 positive clones for full-length IgG sequencing and sequence analysisSequencing report of one clone; ELISA data2 weeks
    DIMA mAbs production and validationAntibody production and identification antibody mass production and purification; antibody function identificationAntibody production, purification and QC validation4 weeks