Since its establishment, Kerun biology has been specialized in prokaryotic and yeast expression platforms, and has its own characteristics in the pilot process development and amplification of biological macromolecular drugs, inclusion body renaturation, long-term expression, nano antibody preparation and other technologies.

(1) Inclusion body protein refolding technology platform

After years of exploration, the company has established a set of inclusion body renaturation technology with independent technology system, and mastered a series of core technologies such as inclusion preparation technology, inclusion body denaturation technology, inclusion body renaturation technology and inclusion body renaturation technology rich in disulfide bond. The technology platform has high renaturation protein concentration (1 ~ 2G / L), high renaturation yield (30% ~ 50%), short renaturation time (20 ~ 24 hours) It is suitable for proteins rich in disulfide bonds.

This technology platform has established a 20L ~ 80L inclusion body renaturation technology platform, and completed the renaturation process development of K07 project, K12 project, 015 project and other inclusion body projects. The inclusion body renaturation technology established by our company includes a set of efficient renaturation formula screening and process design of renaturation scheme, which can quickly evaluate the protein renaturation and obtain a feasible renaturation process. At the same time, the established refolding process is scalable and can meet the application requirements of pilot scale and production scale. The inclusion body refolding technology established by our company can achieve a refolding yield of 20% ~ 50% at a high refolding protein concentration of 1 ~ 2G / L, which is at the leading level in the industry.

(2) Nano antibody technology platform

At present, the nano antibody mutant library under construction is mainly a technical platform to provide functional originals for the company's innovative drug projects.

This technology finds the active region related to the affinity of nano antibody by analyzing the protein structure of nano antibody and the amino acid sequence of antibody variable region; Then the key amino acid sites were found by alanine scanning, and then the key amino acid sites were saturated mutated to construct a saturated mutant library. Finally, through the affinity detection of nano antibody mutants in the mutant library, the functional originals of nano antibodies that meet the needs of project development are found.

(3) Long term drug technology platform for albumin nano antibody fusion

The company's long-term drug technology platform is a biomolecular long-term platform based on albumin nano antibody. Albumin nano antibody can prolong the drug half-life by means of the protective mechanism of neonatal Fc receptor (FcRn) against albumin in human body. The biological macromolecular drugs fused with albumin nano antibody can extend the half-life from several hours to 20 days. By screening the saturated mutant library of nano antibody, we can find the albumin nano antibody with appropriate affinity that meets the needs of molecular design. At the same time, we can also find pH dependent nano antibodies through the screening of mutant library, so as to help the fusion drugs obtain the maximum pharmacodynamic activity.

At present, relying on the long-term technology platform of albumin nano antibody, we have developed a long-term growth hormone. At present, the project has preliminarily completed the concept verification of drug molecules. We screened a pH dependent HSA nanoantibody (low affinity at high pH and high affinity at low pH) through the albumin nanoantibody mutant library. The nano antibody is fused with growth hormone, and the fusion protein has the characteristics of long half-life and dynamic release in human body. Compared with the existing growth hormone drugs, this molecule has better efficacy and safety, and is expected to become a first in class product. The project is expected to apply for an international patent this year. It is an innovative drug with independent intellectual property rights. The project will enter the CMC development stage in the second half of the year.

In addition, relying on the long-term technology of albumin nano antibody, we have also developed an ADC drug molecule with CD123 as the target. The project has also completed the conceptual verification of molecules. The project is positioned as a first in class innovative drug project.

(4) Yeast high density expression technology

The company has a mature yeast expression system and has been approved as the national "Eleventh Five Year Plan" major science and technology special project - "major new drug creation" yeast expression recombinant protein drug pilot scale-up technology platform.