Creative Biolabs is glad to introduce a unique antibody stability improvement service. With the consistent growth of therapeutic antibodies in global market, many efforts have been made to improve the engineering technologies, safety and efficacy of therapeutic antibodies, among which stability is one of the most important functional requirements for the use of antibodies in therapeutic and diagnostic applications.

Fig. 1 Somatic Mutations to Improve Antibody Stability. (Wang et al. 2013)

Antibody Stability Improvement Service

Creative Biolabs has extensive experience in thermal stable antibody screening and optimization services. In addition to thermal stable scFv/Fab screening, we have particularly developed a sequence-oriented, partially-rational engineering strategy for improving thermal stability of antibody and antibody fragments. Based on our expertise in antibody affinity improvement, we are familiar with the amino acid changes that have been observed in functional antibodies; we identify the minimal potential sites for stability improvement and screening for candidates which will not affect and even increase the binding affinity, through which dramatic stabilization can be achieved and the procedure can be greatly simplified compared with conventional randomization approaches. The scFv fragments with increased thermal stability can retain their binding activities at 65-70°C for over 90 minutes.

Fig. 2 Stability Assessment of Antibody Variants. (Wang et al. 2013)

Besides stability improvement of antibody fragments, Creative Biolabs' proprietary strategy has also been successfully applied to full-length therapeutic antibodies. Quite a number of the optimized anti-cancer therapeutic antibodies have been generated that have a 10 °C or higher melting temperature (T_m) compared to the wild type antibodies. Potential benefits of stabilized antibodies also include increased serum half-life as well as reduced immunogenicity. Particularly, it is worth mentioning that stabilized antibodies usually have better solubility and expression level.

Advantages of the Antibody Stability Improvement Platform

• Systematic, rapid, cost-effective and highly reliable.
• Engineered antibody is usable in less optimal and extreme environments.
• Antibody stability level can be adjusted to create multiple products from a single antibody.

Other optional antibody engineering services:

• Antibody Affinity Maturation
• Simianization of Non-monkey Antibodies
• Monoclonal Antibody Caninization Service
• Monoclonal Antibody Murinization Service
• Custom Cysteine Modification in Antibody

Published Data

• High-Throughput Screening of Antibody Variants for Chemical Stability

Fig. 3 Impact of light chain mutations on affinity for target (KD) and resistance to thermal stress-induced specific activity loss. (Danielle M. DiCara, 2018)

Evaluation of the developability of therapeutic antibody candidates facilitates drug discovery and enables early detection of undesirable antibody instability. Here, researchers developed a high-throughput method for detecting antibody candidates that was used to characterize asparagine deamidation. They used the assay to identify a mutation that stabilizes the key asparagine. In this study, a total of 90 antibody variants were incubated under thermal stress to induce deamidation and screened for affinity and total binding capacity. The results showed that mutations in five residues downstream of unstable asparagine greatly reduced deamidation. The scientists then confirmed the predictions through LC-MS analysis and evaluation. This method of high-throughput antibody stability screening at the early stages of antibody discovery will help accelerate the development of therapeutic antibodies.

FAQ

1. What is antibody stability improvement, and why is it important?

   Antibody stability improvement refers to the process of enhancing the physical and chemical stability of antibodies to extend their shelf life, improve their resistance to aggregation, and maintain functionality under various storage and operational conditions. It is crucial for therapeutic and diagnostic applications, ensuring that antibodies perform consistently and effectively in clinical settings.

2. What methods are commonly used to improve the stability of antibodies?

   Common methods for improving antibody stability include engineering the antibody's framework regions, optimizing the glycosylation patterns, adjusting the formulation conditions such as pH and buffer components, and using molecular chaperones or stabilizing agents. Each approach targets different instability issues, like aggregation, denaturation, or degradation over time.

3. How can computational tools assist in improving antibody stability?

   Computational tools can predict antibody stability by analyzing the sequence and structure to identify potential instability hotspots. These tools can guide the modification of amino acid residues prone to aggregation or deamidation. They also assist in simulating the effects of modifications on the antibody's structure and stability, thereby streamlining the development of more robust antibodies.

4. What are the challenges in antibody stability improvement?

   Challenges in antibody stability improvement include maintaining the antibody's binding affinity and specificity while enhancing stability, predicting how modifications will affect overall stability, and ensuring that the improved antibody can be produced efficiently without increased production costs. Balancing these factors is critical to successful antibody development.

5. Can antibody stability be assessed during the early stages of development?

   Antibody stability can and should be assessed early in the development process. Techniques such as differential scanning calorimetry (DSC), size-exclusion chromatography (SEC), and surface plasmon resonance (SPR) can be used to evaluate an antibody's stability profile. Early assessment helps in identifying stable candidates and optimizing them before scaling up production.

Resources

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All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.