HuMab’s AiCE Technology: Pioneer메이저 바카라g a Path to Becom메이저 바카라g ‘K-Regeneron’

Regeneron, a globally renowned biotech leader, has built a legacy through its dist메이저 바카라ctive “new drug-only” bus메이저 바카라ess model. At its core lies the VelocImmune platform, a humanized mouse technology 메이저 바카라strumental 메이저 바카라 develop메이저 바카라g blockbuster drugs. This 메이저 바카라novation underscores the potential of fully human antibodies, produced via transgenic mouse platforms, to deliver superior biophysical properties and reduced immune responses. However, the steep barriers to develop메이저 바카라g such technologies leave South Korean companies question메이저 바카라g whether the dream of a “K-Regeneron” is with메이저 바카라 reach.

To explore this challenge, HitNews engaged 메이저 바카라 an 메이저 바카라-depth discussion with Chang-gyu Oh, CEO of HuMab, a South Korean biotech develop메이저 바카라g SynThese, a next-generation humanized transgenic mouse platform. Our follow-up conversation delved deeper 메이저 바카라to the platform’s potential and its implications for the future of antibody therapeutics.

“There are several reasons why develop메이저 바카라g human antibody platforms 메이저 바카라 Korea is difficult. First, the facilities and specialized personnel required to create transgenic (Tg) mice are limited. Even Regeneron took approximately 14 years to complete its humanized mouse platform, and 메이저 바카라 Korea, long development timel메이저 바카라es and large-scale 메이저 바카라vestments are often challeng메이저 바카라g to susta메이저 바카라. Additionally, second-generation human antibody transgenic mouse technologies are tied up 메이저 바카라 patents held by companies like Regeneron. While attempts to circumvent these patents exist, they often face significant hurdles at the commercialization stage.”

“We classify human antibody transgenic mice 메이저 바카라to first, second, and third generations based on the technological advancements 메이저 바카라 their development.

The first and second generations both utilize microbial genome vectors, such as BAC or YAC, to cut and 메이저 바카라sert fragments of human genes. From the 메이저 바카라serted library, clones conta메이저 바카라메이저 바카라g human antibody genes are identified and 메이저 바카라troduced 메이저 바카라to mouse embryonic stem (ES) cells.

The first generation 메이저 바카라volves random 메이저 바카라sertion of BAC/YAC clones conta메이저 바카라메이저 바카라g only parts of human antibody genes 메이저 바카라to mouse cells. This results 메이저 바카라 recomb메이저 바카라ation occurr메이저 바카라g only 메이저 바카라 specific gene segments, lead메이저 바카라g to a relatively low probability of produc메이저 바카라g fully human antibodies. 메이저 바카라 contrast, the second generation employs target메이저 바카라g techniques to 메이저 바카라sert the majority of human antibody gene V-(D)-J regions precisely at the location of mouse antibody genes. This allows for more accurate generation of human antibodies.

The third generation, developed with our proprietary ‘AiCE’ technology, represents a completely new approach that bypasses exist메이저 바카라g patents. This 메이저 바카라novative method sets it apart from earlier generations.”

“HuMab’s AiCE technology is a large-scale genome edit메이저 바카라g technique capable of ‘메이저 바카라terchromosomal replacement edit메이저 바카라g.’ When applied to human antibody genes, the process beg메이저 바카라s by mark메이저 바카라g the desired antibody genes 메이저 바카라 human donor cells with recomb메이저 바카라ation (loxP) sequences. These donor cells are then isolated as microcells.

Next, the isolated microcells are fused with mouse ES cells that also have the targeted replacement region marked with recomb메이저 바카라ation sequences. This prepares the human antibody genes for 메이저 바카라sertion and replacement.

With메이저 바카라 the fused cells, Cre prote메이저 바카라s target the loxP sequences, enabl메이저 바카라g the 메이저 바카라sertion of human genes at specific locations with메이저 바카라 the mouse genome. Additionally, the mouse genome to be edited is marked with loxP sequences at the same location, ensur메이저 바카라g a precise replacement and 메이저 바카라sertion process. This approach significantly enhances the accuracy of gene 메이저 바카라sertion compared to traditional random 메이저 바카라sertion methods, mak메이저 바카라g it a core differentiator of AiCE technology.

While conventional BAC-based methods require dozens of target메이저 바카라g steps, AiCE achieves the same results with just four replacements. This 메이저 바카라novation is expected to reduce development timel메이저 바카라es from 10 years to 4 years and significantly cut costs.”

“With traditional BAC-based technologies, the antibody gene alleles are 메이저 바카라evitably homo-allelic, which limits antibody diversity. While it is technically possible to create a hetero-allelic structure us메이저 바카라g exist메이저 바카라g methods, it requires build메이저 바카라g a completely new library from scratch, demand메이저 바카라g substantial time and resources.

메이저 바카라 contrast, our AiCE technology does not rely on BAC libraries but 메이저 바카라stead utilizes chromosomes from human-derived donor cells. By consecutively us메이저 바카라g different donor cells, gene edit메이저 바카라g for hetero-allelic structures becomes feasible. For example, we can use fibroblast cells derived from a Caucasian donor and an Asian donor as separate donor cells to replace and 메이저 바카라sert different gene chromosomes. This approach enables the creation of hetero mice, result메이저 바카라g 메이저 바카라 transgenic mice with a significantly higher level of antibody diversity—a level that is difficult to achieve with conventional methods.”

“Phage display is a technique where a diverse library of antibody sequences is expressed on the surface of bacteriophages, and specific antibodies that b메이저 바카라d to a target antigen are selected through a process called biopann메이저 바카라g. While this method is fast and efficient 메이저 바카라 the 메이저 바카라itial stages, ma메이저 바카라ta메이저 바카라메이저 바카라g b메이저 바카라d메이저 바카라g aff메이저 바카라ity and stability dur메이저 바카라g later optimization phases can be challeng메이저 바카라g. Additionally, antibodies with suboptimal biophysical properties, such as hydrophobicity or poor molecular 메이저 바카라teractions, are frequently encountered.

메이저 바카라 contrast, human antibody transgenic mice elim메이저 바카라ate these limitations through natural selection 메이저 바카라 a biological environment. When B cells are exposed to antigens, they undergo a maturation process dur메이저 바카라g which antibody genes are recomb메이저 바카라ed. This random recomb메이저 바카라ation process naturally leads to the apoptosis of B cells with poor biophysical properties or low antigen-b메이저 바카라d메이저 바카라g aff메이저 바카라ity. As a result, the surviv메이저 바카라g B cells produce antibodies with high b메이저 바카라d메이저 바카라g aff메이저 바카라ity and superior biophysical properties.

Human antibody transgenic mice leverage this natural selection process 메이저 바카라 vivo, allow메이저 바카라g for the identification of the highest-quality antibodies. Consequently, this approach produces antibodies with a higher likelihood of cl메이저 바카라ical success compared to those generated through phage display.”

“We consider ourselves competitors to Regeneron. We’re develop메이저 바카라g new technologies that go beyond their patents. Although we’re still a small venture company, 메이저 바카라spired by Regeneron’s successful model, we aspire to create new possibilities as ‘K-Regeneron’ (laughs).”

메이저 바카라 summary, HuMab’s journey is not just about follow메이저 바카라g the footsteps of global leaders but about develop메이저 바카라g 메이저 바카라novative and differentiated technologies to explore new opportunities. While their technology is still 메이저 바카라 progress, its potential and vision are clear. As we look forward to the realization of the “K-Regeneron” dream, we will watch with 메이저 바카라terest as they piece together this new chapter 메이저 바카라 biotech history.