Humanization and Affinity Maturation

Humanization and Affinity Maturation Overview

Methods for humanizing antibodiesSince the approval of Orthoclone Okt3, a mouse-derived monoclonal antibody drug that reduces the natural immunity of organ recipients (such as kidneys) by the US FDA in 1986, monoclonal antibody drugs have been developed for nearly 36 years. During this period, the development of monoclonal antibody drugs has been flourishing, and new technological forms have emerged one after another.

What is humanization of antibodies?

The first chimeric antibody drug is Abciximab. Chimeric antibodies are composed of mouse antibodies and human antibodies. The constant region is composed of human amino acid sequences, while the variable region responsible for binding to antigens is composed of mouse amino acid sequences. Then came the humanized antibody drugs, which further replaced the mouse-derived amino acids in the variable region of the chimeric antibodies with human-derived amino acids, so that in the end, except for the key amino acids in regions such as CDR still retaining mouse-derived amino acids, other parts were replaced with human-derived amino acids. Finally, in humanized monoclonal antibodies, the proportion of human-derived amino acid sequences reached 90%, or even more than 95%.

Why is it necessary to humanize antibodies?

The amino acid composition of murine monoclonal antibody drugs differs from that of humans, which can attract the attention of the immune system, thereby causing an immune response in the body. This leads to the production of human anti-murine antibodies (HAMA), which results in the rapid clearance of murine monoclonal antibodies in the human body, shortening the half-life, and thus limiting the clinical efficacy of murine antibodies. In a few cases, murine antibodies can cause severe allergic reactions, even leading to the death of individual patients.

Methods for humanizing antibodies

The biggest drawback of humanized monoclonal antibody technology is the lack of a universal method. Each antibody molecule needs to be humanized through individual analysis, molecular modeling, extensive modification, and trial and error.

Kyinno has independently developed an AI and structure-based fully automatic antibody humanization integrated algorithm platform. This platform integrates powerful functions such as antibody structure modeling, selection of human templates, CDR-grafting, CDR/SDR transplantation, modification site modification, patent analysis, solubility, stability, charge and half-life, immunogenicity and a series of antibody humanization and drug-related analysis and modification optimization.

The process is shown in the following figure. The degree of humanization can reach 95%-97% or even higher. At the same time, the final humanization design also removes related potential risk points, such as potential post-translational modification sites (deamination, isomerization, oxidation, glycosylation, etc.), immunogenic sites. It also includes optimization of isoelectric point and surface charge, surface hydrophilicity and hydrophobicity, solubility, stability and so on. Relying on the establishment of this platform, it avoids individual analysis, molecular modeling, extensive modification and trial and error in the process of humanization, not only improves efficiency and success rate, but also greatly shortens the entire R&D cycle of antibody drugs, reduces costs and reduces error rates.

The final humanized antibody also avoids a series of problems caused by post-translational modifications and immunogenicity that lead to poor drug properties and high risks in the later stages.

All Antibody Discovery Services

Hybridoma technology is the bedrock of antibody discovery, merging immunized cells to generate monoclonal antibodies. This ensures consistency, high specificity, and high yield for therapeutic and diagnostic applications.

Single B cell screening represents a breakthrough in antibody discovery. Using state-of-the-art technology to isolate, sequence, and analyze individual B cells, ensuring precise identification of specific antibodies for novel treatments.

Utilizing advanced biotechnology, our engineered bispecific antibodies bind two distinct targets. This innovation has the potential to revolutionize therapeutic strategies, heightening specificity, expanding treatment options, and paving the way for future medical advancements.

Taking advantage of camelid-derived nanobodies, we present a distinct antibody structure providing exceptional therapeutic versatility. This innovation leads to innovative approaches to treatments and diagnostics and broadens the modern medical solutions.
In silico developability assessment, transforming biomedicine by providing groundbreaking approaches to predicting antibody developability. Leveraging advanced computational insights, streamline research processes, enhance therapeutic product robustness, and accelerate innovative drug discovery.
With our profound expertise, we optimize antibodies for human compatibility, boosting therapeutic outcomes. Reducing adverse reactions, we lay the groundwork for innovative, patient-focused personalized medicine, customized for each individual.
Our comprehensive assessment of drug potential and immune responses guarantees therapeutic safety and efficacy. This rigorous process is vital in bridging the transition from lab research to successful clinical stage implementation.
Using antibodies with high specificity, we guarantee precise binding targets for CAR-T cells and biologics. This meticulous approach is foundational to therapeutic success and patient outcomes. Promoting next-generation healthcare solutions.
Targeting G-protein coupled receptors, we access an expansive therapeutic domain. Concentrating on these essential proteins, we not only enhance drug efficacy but also pioneer breakthroughs, broadening horizons in modern drug development.
Nanobodies, featuring high affinity and stability, revolutionize therapeutic approaches. Their unique properties make them invaluable, especially in the areas of targeted drug delivery, advanced diagnostics, and innovative disease intervention strategies.
KYINNO sets the standard, prioritizing high-quality antibody production. We emphasize unmatched consistency, purity, and reliability, setting industry guidelines, fostering trust, and accelerating groundbreaking drug discovery and innovative research endeavors.
Bispecific antibodies from KY-CLC bind two distinct antigens, offering advanced therapeutic avenues, enhancing drug delivery, and increasing the potential for successful patient outcomes.
Nanobodies, known for their small molecular weight, high affinity, stability, permeability, and cost-effectiveness, have demonstrated tremendous potential in disease …