Antibody Developability Improvement

Do you have a candidate therapeutic antibody that has suboptimal manufacturing characteristics such as low yield, high aggregation, or purification difficulties? Our dedicated team of antibody experts leverages 25 years of expertise our proprietary AI technology to transform your antibody into a successful therapeutic. Our antibody developability improvement service helps you make informed decisions, saving you time and resources in the drug development process. With 3 therapeutic antibodies on the market and 30+ antibodies in preclinical and clinical phases of development, you can trust us to deliver the insights you need to avoid antibody developability pitfalls and accelerate your clinical project.

Antibody Developability Assessment of Early-Stage Biologics

At ProteoGenix, we are proud to offer our clients antibody developability improvement services that can transform your research into life-saving treatments.

Costly delays and clinical failures can be prevented by simply identifying the developability profile of an antibody during the early stages of the drug development process. You can take the risk to analyze and improve your antibody’s developability in-house or you can hire an expert team to do it for you.

At ProteoGenix, we have the tools and experience needed to rigorously evaluate your antibody’s developability profile to help you circumvent the pitfalls associated with antibody manufacturing, clinical development, and the evaluation of clinical efficacy. We do this by leveraging our team’s 25 years of average experience and artificial intelligence to take the guesswork out of antibody developability. By identifying potential issues early, we help our clients optimize their development pipeline, reduce costs, and bring effective treatments to patients faster.

Antibody Developability Services

Our antibody developability services involve evaluating and optimizing the physical and chemical properties of your antibody to increase the probability it becomes a licensed biologic.

This includes a range of services such as assessing the antibody’s stability, liabilities, solubility, aggregation propensity, immunogenicity, and affinity to its target antigen. Other services include evaluating the antibody’s manufacturability, such as assessing the yield and purity of the antibody during production or optimizing the antibody’s formulation to improve its shelf life and stability.

Here is what you can expect when using our antibody developability improvement service:

• Feasibility Study: We begin by conducting a feasibility study on your antibody of interest to determine if it can benefit from our antibody developability service. We provide a detailed report of our analysis and give you a quote for the next step. Following our report, you can choose to proceed to our AI Developability Analysis step (Go/No-Go decision point).
• AI Developability Analysis: If the feasibility study is successful, we move on to the developability stage. We provide a detailed report of your antibody’s projected developability using our machine learning AI tool. The report includes amino acid replacement suggestions to improve your antibody’s developability. You can choose to proceed to the next optional Go/No Go decision point.
• Express Recombinant Variants: Once the AI developability analysis is complete, we proceed to express the recombinant variants in our proprietary XtenCHO cell line, generating superior antibody yields, purity, and proper antibody post-translational modifications. Following antibody expression, we deliver the following:

• Recombinant antibody variants (1 mg purified antibody)
• cDNA in the expression vector
• cDNA sequences of antibody variants

You have the option to proceed to the next stage and allow ProteoGenix to rigorously test the biophysical properties of your antibody variants (the last Go/No-Go decision point).

• Test Antibody Variants: The final stage involves testing the variants to determine if the antibody developability profile has improved. To do this we use an array of sophisticated approaches to test:

• Antigen Affinity (ELISA)
• Antibody Interactions (Biacore Surface Plasmon Resonance)
• Thermal Stability (Differential Scanning Calorimetry and Differential Scanning Fluorimetry)
• Stability (at room temperature, storage, freeze-thaw cycles, etc.
• Antibody Aggregates (Size exclusion chromatography-HPLC)

Our antibody developability improvement services identify and address potential issues early on in the drug development process, to fast-track your antibody’s progression from bench to bedside.

Antibody Developability Assays

There are various antibody development assays that we can perform to assess and improve the developability of antibodies. Here are some examples:

• Thermal stability assay: This assay evaluates the thermal stability of an antibody by measuring its unfolding temperature (Tm) using techniques such as differential scanning fluorimetry (DSF). This assay helps to identify the conditions that promote the stability of the antibody.
• Aggregation assay: This assay evaluates the propensity of an antibody to aggregate, which can impact its efficacy and safety. Techniques such as size exclusion chromatography (SEC-HPLC) can be used to measure the size and distribution of the aggregates formed.
• Solubility assay: This assay evaluates the solubility of an antibody under different conditions such as pH, salt concentration, and temperature. This assay helps to identify the conditions that promote the solubility of the antibody.

Antibody Yield Assessment: Our antibody yield analysis measures the amount of antibody produced among different antibody variants during the manufacturing process to assess their manufacturing potential. This helps to ensure that the most potent clinical antibody variant is selected that also has the best manufacturing profile. This step ensures cost-effective and efficient production of therapeutic antibodies.

Antibody Developability of Modified Antibodies

Modifying an antibody, such as creating a bispecific antibody or an antibody-drug conjugate (ADC), can change its developability profile. The process of modifying an antibody can introduce new structural features, such as additional domains or conjugated drug molecules, that can affect the antibody’s stability, solubility, and antigen-binding properties.

Therefore, it is important to evaluate the developability of modified antibodies early in the drug development process, to ensure that the modifications do not adversely affect the antibody’s therapeutic properties or its ability to be manufactured at scale. Additionally, modifying an antibody can require new analytical methods and manufacturing processes, which can also impact the developability of the final product.

Bispecific Antibody Developability

The assessment of bispecific antibody developability can involve some additional considerations compared to a traditional monoclonal antibody. This is because the dual antigen-binding properties of bispecific antibodies can impact their developability.

Some of the specific considerations when assessing the developability of a bispecific antibody include:

• Stability: Bispecific antibodies may have a higher propensity for aggregation and precipitation compared to their monoclonal antibody precursors. Therefore, assessing the stability of a bispecific antibody is critical to ensure that it can be manufactured at scale and maintain its therapeutic properties.
• Solubility: The additional antigen-binding domains in a bispecific antibody can affect its solubility. Evaluating the solubility of a bispecific antibody is important to ensure that it can be formulated and stored correctly.
• Immunogenicity: Bispecific antibodies can have a higher potential for immunogenicity compared to monoclonal antibodies. Therefore, assessing the immunogenicity of a bispecific antibody is important to ensure its safety and efficacy in patients.
• Manufacturing: Bispecific antibodies can have more complex manufacturing processes compared to monoclonal antibodies. Therefore, evaluating the manufacturability of a bispecific antibody is important to ensure that it can be produced consistently and at a reasonable cost.

The assessment of the developability of a bispecific antibody involves similar considerations to monoclonal antibodies but with some additional factors specific to the bispecific format. Therefore, it is important to tailor your antibody developability goals to the final modified antibody for the best results.

Antibody Drug Conjugate Developability

There are different ways to assess the developability of an antibody-drug conjugate (ADC) antibody compared to a traditional monoclonal antibody. ADCs are complex molecules that consist of an antibody linked to a cytotoxic drug, and this complexity can affect their developability.

Some of the key factors to consider when assessing the developability of an ADC antibody include:

• Stability: ADCs are prone to degradation, and it is important to assess their stability over time to ensure that the drug remains bound to the antibody.
• Drug-to-antibody ratio (DAR): The DAR is a measure of the number of drug molecules attached to each antibody molecule, and it is important to optimize the DAR to achieve maximum therapeutic benefit.
• Conjugation site: The site of conjugation between the antibody and the drug can affect the stability and efficacy of the ADC.
• Immunogenicity: ADCs can induce an immune response, which can affect their safety and efficacy.
• Pharmacokinetics: ADCs have complex pharmacokinetics, and it is important to assess their distribution, metabolism, and elimination from the body.

To ensure the successful development of an antibody-drug conjugate (ADC) antibody, it is crucial to assess its developability using methods that are specifically tailored to its unique characteristics. This can be achieved by either conducting the developability assessment yourself or by working with antibody experts who have the knowledge, skills, and tools to improve your antibody’s developability.