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CHIMPS Bispecific Antibodies

Bispecific Antibodies

Correlated and Harmonious Interfacial
Mutation between Protein Subunits

CHIMPS Bispecific Antibody Technology creates bispecific antibodies of natural structure and superior characteristics by substituting very limited amount of amino acids to different amino acids of similar polarity, while maintaining thermostability, physicochemical, and biological characteristics such as ADCC (Antibody-dependent Cell-mediated Cytotoxicity) and CDC (Complement-Dependent Cytotoxicity).

  • Patent TitleBispecific proteins and methods for preparing same
  • Patent No.WO2018016881A1
  • Patent Link

* Ibentrus is part of Aprogen group, and Aprogen holds the all rights for all patents held by Ibentrus

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For example, to prepare a bispecific antibody that has antigen-binding characteristics of both antibody A and antibody B, the DNA for the heavy chain (HA) and light chain (LA) of antibody A, and the heavy chain (HB) and light chain (LB) of antibody B must be transfected to the production cell line. In theory, this results in 10 different combinations of heavy-light chain antibodies. However, out of the 10 possible combinations, only HA:LA + HB:LB combination, where HA and HB are combined into a heterodimer form, HA:HB, and the Fab region of HA, the V-CH1 domain, connects the LA and LB to the Fab region of HB, is the functional bispecific antibody, and the rest of the antibody combinations are byproducts that must be removed during the purification process.

Our CHIMPS technology induces the production cell lines to produce bispecific antibodies with almost 100% purity by introducing only very few numbers of amino acid substitutive mutations that do not alter the hydrophobicity or hydrophilicity of amino acids in an antibody’s heavy and light chains. This results in only the CH2-CH3 domain or Fc of HA, the heavy chain derived from antibody A, and the CH2-CH3 domain or Fc of HB, the heavy chain derived from antibody B, forming a heterodimer. Moreover, the CH1 domain of HA binds only to the CL domain of LA, and the CH1 domain of HB binds only to the CL domain of LA. Hence, with the CHIMPS technology, we can avoid difficult purification steps in removing byproducts with unwanted heavy-light chain combinations, while efficiently producing bispecific antibodies that maintain their natural structure, function, and characteristics.

Technologies from competitors alter the natural structure of an antibody, which results in various side-effects such as 1. decreased immunological functions such as ADCC (Antibody-Dependent Cell-mediated Cytotoxicity) and CDC (Complement-Dependent Cytotoxicity), 2. reduced vascular and tissue permeability, and 3. shortened antibody half-life. CHIMPS technology, on the other hand, can produce bispecific antibodies with 100% purity, while maintaining the natural antibody’s function and properties, directly from the cell cultured media without any modifications to the conventional purification process for monoclonal antibodies.