Custom Antibody Development and Manufacturing: Taking a Customer-Focused Approach

1,500-L bioreactor at Sino Biological.

Business analysts predict that the global market for monoclonal antibody (MAb) therapeutics — including human, humanized, chimeric, and murine antibodies — will expand at a compound annual growth rate (CAGR) of 14.1% from US$178.50 billion in 2021 to $451.89 billion in 2028. Strong demand for MAb products also is spurring on the global market for custom antibody manufacturing, which is projected to grow at a CAGR of 10.6% from $393 million in 2021 to $652 million by 2026 (1).

Driving much of that growth is the rapid rate at which new drug targets are being identified, particularly in the immunotherapy space. As new targets are uncovered, many companies are seeking out recombinant antibodies that can inhibit or activate them. The growing volume of gene-sequence and product-characterization data published openly online is helping researchers to accomplish that goal, which will boost further innovation in the biopharmaceutical industry.

Wide circulation of the initial SARS-CoV-2 gene sequence is one good example of how sharing scientific data helped society at large. Sequence data for SARS-CoV-2 variants continue to be made available quickly. Thus, companies such as Sino Biological can produce recombinant proteins and corresponding antibodies expediently, enabling rapid diagnostic and vaccine development.

A second important shift in the recombinant antibody market is a growing expectation among customers for high-quality products that have undergone considerable characterization. Biopharmaceutical developers want highly polished antibodies of high purity that are fully characterized, including data on their biological activity.

Increasing Numbers of Antibody Formats
In addition to growing rapidly in size, the breadth and depth of the recombinant antibody market are increasing as well. Customers continue to seek out traditional, full-length Immunoglobulin G (IgG) antibodies of human, mouse, rat, rabbit, goat, sheep, dog, and other animals. Novel formats include single-chain antibody fragments, fusion proteins, and bi- and trispecific antibodies, just to name a few. Multispecific antibodies are increasingly common as drug developers seek to overcome the disadvantages of conventional MAbs.

Sino Biological has invested significantly in building the expertise and production platforms needed to synthesize many different antibody formats. Because production needs differ significantly between conventional and novel antibody formats and from one new format to another, we control the cost of process development during early phase research and rapidly determine production conditions that will provide high yield and high purity for a given candidate.

Emergence of Theoretical Sequences
Researchers increasingly are using computational technologies and artificial intelligence (AI) to predict ideal antibody sequences based on target binding sites and other factors. When applying such technologies, there is often a gap between theory and reality. Some sequences cannot be produced readily; extensive knowledge and understanding of protein expression are required to develop expression systems that can generate novel antibodies at high yield and purity.

Sino Biological has established an AI-powered affinity-maturation platform. It applies machine-learning (ML) algorithms to predict the effects of mutations on antibody–antigen binding. Then, our scientists validate those predictions in laboratory experiments.

Continuing Industry Needs
High-Throughput Characterization: Obstacles remain with respect to antibody characterization, particularly for new antibody formats. Typically, characterization requires an array of advanced, complementary techniques, many of which have yet to be developed for high throughput. Thus, Sino Biological has established and optimized a full array of capabilities, including biolayer interferometry (BLI) and surface plasmon resonance (SPR) instruments for biomolecular-interaction analysis.

Many Approaches to Process Optimization: Process optimization for recombinant-antibody production remains a complex process comprising many methods, from codon optimization to stability improvement and yield enhancement. At Sino Biological, we optimize codons for recombinant antibodies using internally developed software. Additionally, our fully optimized platforms take into consideration the vector, host-cell line, culture medium, and culture and purification conditions.

Meeting Needs for High-Quality Recombinant Antibodies
Sino Biological was established in 2007 to focus on recombinant-protein production and antibody development. With headquarters in Beijing, China, and subsidiaries in the United States, Europe, and Japan, the company has more than 900 employees and serves researchers in academia and industry worldwide. Sino Biological works at the forefront of both the bioreagents and contract-research services industries, providing a full slate of high-quality recombinant proteins and corresponding antibodies, as well as custom development and production solutions for particularly difficult projects.

Expression Systems: Drug developers want the secondary and tertiary structures and posttranslational modifications (PTMs) of their antibodies to be as similar as possible to those found in humans. Recombinant proteins and antibodies produced in mammalian cells look and behave more like native human proteins than do those expressed in other hosts. Thus, Sino Biological has amassed an extensive collection of bioactive recombinant proteins made in mammalian cells.

Our proprietary mammalian-cell expression platforms are designed to increase chances for success during manufacture of difficult-to-express proteins and antibodies. To facilitate drug development, we also have other technologies in place, such as the baculovirus vector system for insect-cell expression and the Berkeley Lights Beacon single B-cell screening platform.

Timelines: Before the COVID-19 pandemic, drug companies had felt increasing pressure to reduce the time and cost of drug development and manufacturing. The need for rapid development of COVID-19 vaccines and therapeutics only reinforced that trend. Expectations for even shorter delivery timelines have followed for custom recombinant proteins and antibodies.

Sino Biological is positioned to meet those evolving expectations. For example, in January 2020, we produced key SARS-CoV-2 spike-protein reagents within 11 days. In December 2021, we developed the omicron variant’s receptor-binding domain protein in six days.

We have implemented high-throughput production processes and expanded our capabilities to enable simultaneous pursuit of multiple projects, and additional new laboratories are under construction. As a result, we typically have no waiting line for capacity, even though we are working on more than 1,000 projects at the same time. For example, we can produce 1,000 different antibodies for a customer in two weeks. Sino Biological also can produce material from microgram to kilogram scales. We want to ensure that every researcher worldwide can access products of consistently high quality in the quantities that they need.

Quality Control (QC) Packages: All custom recombinant antibodies manufactured by Sino Biological are delivered with a certificate of analysis that lists standard QC parameters for concentration, purity, and other such attributes. We also provide results from stability studies. Our standard QC package can be customized if, for instance, a client needs a product to exhibit greater purity, lower endotoxin levels, or other specific requirements. Sino Biological’s goals are to incorporate customer-defined specifications in our QC packages whenever possible and to perform additional or modified assays to provide the requested data.

Custom Antibody Services
When a customer needs something unusual, Sino Biological will make it. We are continually expanding our portfolio of antibodies and other bioreagents as well as our custom capabilities for research, development, and manufacturing.

Reference
1 Monoclonal Antibody Therapy Market Size, Share, and COVID-19 Impact Analysis, by Type (Human MAb, Humanized MAb, Chimeric MAb, and Murine MAb), by Application (Cancer, Autoimmune Diseases, and Others), by Distribution Channel (Hospital Pharmacy, Retail Pharmacy, and Online Pharmacy), and Regional Forecast, 2021–2028. Fortune Business Insights, August 2021; https://www.fortunebusinessinsights.com/monoclonal-antibody-therapy-market-102734.

Rob Burgess, PhD, is chief business officer; Amy Sheng, PhD, is head of the CRO program; and Lillith Elmore is an account executive, all at Sino Biological US Inc.; 1-215-583-7898; [email protected]; https://www.sinobiological.com.

This content has been created in collaboration with Pharma’s Almanac.