Y-BIOLOGICS

The Importance of Fully Human Antibody Therapeutics

What are Fully Human Antibodies?

Antibodies from human sources consisting solely of fully human sequences: No murine sequences, which are commonly used in animal testing; Produced by using phage display technology to identify the desired human antibody genes, and then introducing the desired sequences into transgenic mice; Simplifies manufacture of antibody therapeutics due to lower expected immunogenicity compared to animal-derived antibody sequences

Antibody Development Trends	1970s Murine Antibodies Mouse Antibody Sequences	1980s Chimeric Antibodies Human Antibody Sequences	1990s Humanized Antibodies Human Antibody Sequences	Reduced Immunogenicity and Side Effects 2000s Fully Human Antibodies Human Antibody Sequences
Ratios in Global Antibody Therapeutics Development	1990~1999 2000~2010

Pharmacokinetic properties determining a drug’s safety and efficacy impacted by immunogenicity
Demonstrated advantage of fully human antibodies or at least humanized antibodies in clinical trials.

Number of Approved Antibody Therapeutics (Cumulative Total)

*Source: Immunotherapy Vol. 11, No. 2

The number of humanized or fully human antibodies among FDA-approved antibody therapeutics has been increasing each year.

Human
Humanized
Chimeric
Murine

The First Step in Developing a Fully Human Antibody Therapeutic from a Targeting Protein

Phage Display Technology

In phage display, genetic information of a target protein is inserted into the genome of a phage so that the target protein is exposed on the surface of the phage, enabling the production of fully human antibodies that are nearly identical to antibodies produced by the human body.

Phages, the smallest type of viruses, mainly infect bacteria. Because of their miniscule size, hundreds of billions can exist in just 1 mL of solution.

After the antibodies are presented on the surface of a phage, the process of selecting an antibody that binds to the target antigen becomes much simpler. Antibody presentation on the surface of the phage can be accomplished by inserting the genes of a human antibody into the phage’s genome through genetic engineering.

All antibody genes produced by a human body can be inserted into phage genes to create a collection of phages displaying the diverse antibodies. This collection of antibody-presenting phages is called a phage display library or human antibody library.

The key to producing a comprehensive human antibody library is to obtain every gene for each antibody produced in the human body and use molecular biology techniques that insert the antibody genes into the phage genes without any loss.

Ymax®-ABL, the Initiation Point of all Novel Therapeutic Antibody R&D at Y-Biologics

01
World-class Fully Human Antibody Library

World-class naïve cDNA library of fully human antibodies

More than 100 billion different antibody genes presented through phage display, a technology using genetic recombination to express proteins on the surface of viruses and enabling mass production of antibodies by finding specific enzymes that bind to antibodies
02
Launchpad for Each Pipeline Projects

All novel antibodies discovered independently are selected from Ymax®-ABL
03
Increased Diversity and Excellent Antigen Binding

Diversity enhanced by using a shuffling strategy during the manufacturing process

Excellent antigen binding
04
Clinical Trials for YBL-006 in 3 Countries

YBL-006, an anti-PD-1 immune checkpoint inhibitor, is a new therapeutic antibody candidate discovered from Ymax®-ABL and developed in-house that is currently undergoing Phase 1 clinical trials in Korea, Australia, and Thailand
05
High Sequence Similarity to Human Antibodies

Lower immunogenicity, or the ability of an antigen to trigger an immune response, compared to synthetic libraries

Superior antibody productivity and physical properties compared to synthetic libraries

Discovering Suitable Antibodies through Biopanning

Biopanning is the process of selecting an antibody pool that binds to a specific antigen from an antibody library. In our pursuit of discovering top-tier antibodies, this process is just as important as the diversity of our Ymax®-ABL library.

In acknowledgement of its importance, Y-Biologics is optimizing and applying a wide range of biopanning methods. In particular, we are developing and applying novel cell panning technology to antigens for antibodies which are challenging to screen and select.

Production of Antibodies with High Potential for Development

An antibody library
with high diversity
A phage display system for labeling target proteins
Diverse biopanning methods to find the desired antibodies
An efficient system enabling prompt
analysis of discovered antibody
High quality of
antibodies discovered from the library