Common Light Chain Antibody

Kyinno's Bispecific Antibody Platform with Common Light Chain Mice

Bispecific antibody (BsAb) is engineered antibody that can simultaneously bind to two antigens or epitopes. Due to this multifunctionality, it have gradually become the focus of antibody drug development. BsAb can activate immune cells by connecting them to tumor cells via molecular bridging; it can also block the interation between the two antigens and their corresponding ligands, leads to the inhibition of the antigen-mediated signaling pathways which were related to tumor cell proliferation, differentiation and metastasis; bispecific ADC (Antibody-Drug-Conjugated), which was building on the BsAb, has been an important direction for the future development of ADC, with the high specificity, high endocytosis and low cytotoxicity. As of August 2023, twelve BsAbs were approved and the global market size was $ 5.8 billion. The expected market will reach to at least tens of billions by the year 2030.

The concept of bispecific antibodies



In the year 2022, we witnessed an explosion of bispecific antibodies with a total of six BsAbs gaining regulatory approval and entering the market. This number exceeds the total for previous years. Towards the end of the year, two novel bispecific antibodies were featured in the prestigious New England Journal of Medicine. The bispecific antibody field is poised for success, with nine bispecific antibody drugs having received regulatory approval to date. Analyzing the nine approved bispecific antibodies, five maintain the natural antibody conformation, indicating a potentially higher success rate in developing these new structural drugs. Among these five, Emicizumab is a common light chain bispecific antibody, while Amivantamab and Teclistamab are based on Genmab’s duobody technology. Mosunetuzumab and Faricimab employ Genentech’s Crossmab technology. While Genmab’s duobody technology requires the development of two antibodies and their in vitro assembly, Crossmab technology is still under patent, and its development process is complex. When considering aspects like production and pharmaceutical development, the common light chain technology undoubtedly holds several advantages.
approved bispecific antibodies

To support the development of bispecific antibodies, Kyinno has successfully developed the Common Light Chain (KY-CLCTM) Mouse technology platform. The KY-CLC-mouse features no lambda (λ) light chain expression and fully identical kappa (κ) light chains, which offer excellent solubility and stability (protected by patent). KY-CLC-mouse enables rapid and efficient screening for high-affinity, highly specific antibodies against all validated targets. Bispecific antibodies assembled using this platform are comparable to monoclonal antibodies in terms of expression, purification, stability, and other critical attributes.

We welcome collaboration to explore the opportunities this platform provides.

Common Light Chain (KY-CLCTM) Mouse technology platform

Affinity tests of LAG3/PD1, PD-L1/EGFR, MET/EGFR bispecific antibodies：

Affinity tests of LAG3 PD1, PD-L1 EGFR, MET EGFR bispecific antibodies

Case Study

1. LAG3/PD1 bispecific antibody

Binding affinities of bispecific antibody KA-1833 against PD1 and LAG3 to PD1-HIS and LAG3-HIS

LAG3 PD1 bispecific antibody

 

2. Blocking activity of bispecific antibody KA-1833 against PD1 and LAG3

Blocking activity of bispecific antibody KA-1833 against PD1 and LAG3

3. SEC-HPLC and SDS-PAGE

SEC-HPLC and SDS-PAGE

4. PD1

PD1

5. LAG3

LAG3

6. PDL1

PDL1

7. EGFR

EGFR

7. CD47

CD47

References:

  1. Labrijn AF, Janmaat ML, Reichert JM, Parren PWHI. Bispecific antibodies: a mechanistic review of the pipeline. Nat Rev Drug Discov. 2019 Aug;18(8):585-608.
  2. Bispecific antibodies targeting dual tumor-associated antigens in cancer therapy. Review – Cancer Research. 28 September 2020