April 7, 2022 PAO-04-022-CL-01
The global market for monoclonal antibody (mAb) therapeutics, including human, humanized, chimeric, and murine mAbs, is predicted to expand at a compound annual growth rate (CAGR) of 14.1% from $178.50 billion in 2021 to $451.89 billion in 2028.1 That strong demand is also driving an increase in 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 2026.2
Much of this growth is driven by the rapid rate at which new drug targets are being identified, particularly in the immunotherapy space. As new targets are uncovered, many companies seek to find recombinant antibodies that can inhibit or activate them. The growing volume of sequence and characterization data published openly online is making it easier for researchers to accomplish those goals, which is boosting further innovation in the industry.
The wide circulation of the sequence for the initial SARS-CoV-2 virus that causes COVID-19 is one good example of how sharing sequence data positively impacted society. Sequence data for the spike proteins of variants also continue to be made available very quickly. That allows companies like Sino Biological to produce these recombinant proteins and the corresponding antibodies extremely quickly — as fast as 12 days from nucleotide sequence announcement, which enables rapid diagnostic and vaccine development.
A second important shift in the recombinant antibody market is a growing expectation for higher-quality products with higher levels of characterization. Biopharma developers are no longer seeking simple material produced in pilot runs; they want highly polished antibodies of high purity that are fully characterized, including data on their activity.
One consequence of this shift has been a growing preference for antibodies produced via mammalian cell culture rather than microbial fermentation or using insect cell systems. Drug developers want the secondary and tertiary structures and post-translational modifications (PTMs) of antibodies to be as similar to those found in humans as possible. Recombinant proteins and antibodies produced in mammalian cells look and behave more like they would in a real biological barrier. As a result, over 85% of all proteins manufactured by Sino Biological are produced in mammalian cells today. As the global leader in recombinant technology, Sino Biological has its proprietary mammalian cell culture and recombinant expression platforms, which employ a range of proprietary reagents and processes that are specially optimized, enabling highly efficient expression of proteins and antibodies in HEK293 and CHO cells.
In addition to growing rapidly in size, the breadth and depth of the recombinant antibody market are increasing as well, both for more traditional full-length antibodies and other antibody formats. Sino Biological, for instance, has the expertise and capability to produce full-length IgG antibodies of human, mouse, rat, rabbit, goat, sheep, dog, and other animals. Other formats include single-chain antibody fragments, fusion proteins, and bispecific and trispecific antibodies, to name a few. Multispecific antibodies are becoming increasingly common as drug developers seek to overcome some of the disadvantages posed by conventional full-length mAbs.
Sino Biological has invested significantly in building the skills and expertise needed to synthesize many different antibody formats, including the development of production platforms for these special antibodies that can operate in a high-throughput fashion. Because the production needs vary significantly between conventional and novel antibody formats and from one new format to another, we are able to control the cost of process development during early-phase research and rapidly determine the production conditions that will afford high yield and high purity for a given candidate. Researchers can then put their efforts into downstream activities, such as formulation development and preclinical studies.
The expression and purification of recombinant proteins and antibodies from known sequences is a mature process — as fast as 12 days. The production of theoretical sequences generated using computational/artificial intelligence technologies can be more challenging, however. Computer algorithms are more and more frequently used to predict the ideal sequence for an antibody on the basis of the binding site of the target and other factors, and there is often a gap between the theory and reality. Some of these sequences cannot be readily produced; extensive knowledge and understanding of protein expression are required in order to develop expression systems that can generate these unique antibodies in high yield and purity.
Challenges also remain with respect to antibody characterization, particularly for the newer antibody formats. Typically, a wide range of complementary, advanced techniques must be employed, many of which have not been developed for use in a high-throughput manner. Sino Biological has a full array of capabilities, including affinity analysis, bio-layer interferometry (BLI), and surface plasmon resonance (SPR), that have been optimized in our system. However, in some cases customers require additional analyses that are difficult to achieve as part of a high-throughput screening program and require a more conventional approach.
Process optimization for recombinant antibody production is a complex process that encompasses many methods, from codon optimization to improving stability to enhancing the yield. At Sino Biological, we perform codon optimization for recombinant antibodies using internally developed software. Our system is fully optimized, taking into consideration the vector, cell line, culture media, and culture and purification conditions. As a result, customers can be confident that the processes we develop are highly optimized for their recombinant antibodies.
For mouse or human IgG antibodies, platform processes are applicable, and minimal optimization is typically required. Some antibodies, however, may be unstable and tend to aggregate or degrade under typical production conditions. These molecules can require highly specific culture and purification conditions. For others, the unique format of the antibody may require the use of less common cell lines and process conditions to achieve the process design space in order to determine optimal process conditions. For instance, we may need to screen for the right buffer solutions and potentially develop custom affinity ligands and resins rather than employ protein A to realize an optimum process solution.
Sino Biological’s mission is “To advance life science and improve human health through the provision of superior quality research reagents and CRO services,” and the company is dedicated to producing high-quality recombinant proteins and antibodies.
Sino Biological was established in Beijing and has since grown to be a multinational corporation with about 450 employees and offers alarge selection of full-length bioactive recombinant proteins, the vast majority of which are made in mammalian cells. Within our catalog, we have 6,500 recombinant proteins and a large number of antibodies strategically selected based on their specific targets. We offer both monoclonal and polyclonal antibodies, as well as newer formats and ancillary products, such as ELISA kits.
The overall portfolio of Sino Biological’s bioreagents is sold worldwide through a combination of distributors and internal sales. We received great attention during the COVID-19 pandemic due to the fact that Sino Biological produced the key spike protein reagents within a record 11 days in January 2020 and has developed a comprehensive list of research reagents to support the global fight against SARS-CoV-2, with over 400 antigens and antibodies. These products have been widely used to manufacture rapid antigen and antibody tests, and many of them have received Emergency Use Authorization from the U.S. FDA. In addition to SARS-CoV-2 reagents, moreimmunologists and virologists are now routinely buying products related to other viruses, such as proteins for influenza virus and respiratory syncytial virus (RSV), as well as the corresponding antibodies that bind to them. Sino Biological's ProVirTM collection is the world's largest viral antigen bank, carrying over 1,000 viral products from 380 strains of viruses. As a consequence, Sino Biological has become a leader in the infectious disease bioreagents and CRO services markets.
Soon after Sino Biological was established, the company began offering custom manufacturing and research services in addition to its catalog products to meet the increasing demand for outsourcing partners. The trend toward outsourcing has continued and even increased in recent years. More and more pharmaceutical, biopharmaceutical, biotech, and academic and nonprofit research labs are electing to seek custom recombinant protein and antibody generation rather than invest time and resources in in-house capabilities.
The effort and risk involved in process development for these companies are now much greater, especially for non-traditional formats. By outsourcing to Sino Biological, they can be assured that their custom antibodies will be delivered in a short time frame with high purity and accompanied by comprehensive characterization and bioactivity data. As a result, the percentage of sales revenue derived from these service offerings has grown significantly.
Before the COVID-19 pandemic, the pressure on drug companies to reduce the time and cost of drug development and manufacturing was increasing, but the rapid development of COVID-19 vaccines and therapeutics only reinforced this trend. Expectations for even shorter delivery timelines for custom recombinant proteins and antibodies have followed.
Sino Biological is positioned to meet these evolving expectations. We have implemented high-throughput production processes and expanded our capabilities to enable pursuit of multiple projects simultaneously, and additional new laboratories are under construction. As a result, there is typically no waiting line for capacity, even though we are working on more than 1,000 projects at the same time. As an example, we can deliver 1,000 different antibodies to a customer within three to four weeks.
What makes this possible is standardization of our processes for recombinant antibody production and delivery, starting with gene synthesis and continuing through expression and purification to shipping. Having an effective solution for shipping from China is crucial, as there is a perception that production in China carries significant risk owing to the need to ship product. Our logistics management enables us to provide guaranteed delivery of products, often with shipment times of one week or less. We also have a warehouse of catalog product samples in the United States, which allows us to get samples to customers in a day or two.
Leveraging our platform processes and shipment solutions, Sino Biological is addressing the market need for rapid recombinant antibody production at reasonable cost.
All recombinant antibodies custom manufactured by Sino Biological are delivered with a certificate of analysis containing standard quality control parameters for concentration, purity, and other attributes. The results of stability studies are also provided. This standard quality control package can be customized if there is a need for the purity to be greater than our standard, endotoxin content to be lower, or any other specific requirements. We can also investigate antibody stability under customized conditions (e.g., different pH, temperature, buffer). The goal at Sino Biological is to incorporate customer-defined specifications in our QC packages wherever possible and to perform the additional or modified assays necessary to provide the requested data.
From a business development perspective, there are two issues that must be balanced: speed and protection of client intellectual property. The nature of a project determines its timeline. For antibodies that are in demand and for which the sequence is in the public domain, Sino Biological will often develop production processes and manufacture these products in advance of any specific customer order. Researchers will thus receive these materials very quickly.
For customers that have confidential sequences, work cannot begin until the customer commits to the project. Most often, new relationships begin with a nondisclosure or confidentiality agreement that progresses to a supply or service agreement. These documents are prepared as quickly as possible and provide not only protection of confidentiality but product quality expectations, estimated timelines for deliverables, and cost structures for projects. Our approach, meanwhile, has streamlined the business development aspects of project initiation, minimizing the time before process development work can begin. For clients, we have found that the speed and quality of our business agreements is as advantageous as the speed and quality of recombinant protein/antibody development and manufacturing that Sino Biological provides. It is a win–win situation, because once a client is onboarded for the first time, they tend to return, whether they are seeking a catalog product or custom services.
Recombinant antibodies are complicated molecules with a wide range of physicochemical properties, as well as primary, secondary, and tertiary structures. Process development is not smooth, even when platform approaches are available. Production issues will often arise, particularly for recombinant antibodies based on computer-generated sequences and those involving new formats.
The experience Sino Biological has gained developing manufacturing processes for thousands of antibodies from well-known, conventional IgGs to novel, highly complex multifunctional molecules enables us to overcome the challenges that arise and still develop cost-effective processes that afford high yields of high-purity products within short timelines. Our experience characterizing all of these different types of antibodies also makes it possible for us to develop unique analytical methods for challenging antibodies.
Close communication and trust are also important facets of Sino Biological’s approach to providing custom antibody manufacturing services. Our scientists speak directly with our clients’ technical experts to share knowledge and discuss proposed ideas for resolving production issues. We are open about any hurdles and unexpected problems we encounter and value feedback from our clients based on their past experiences with their projects. For our clients, the interaction is more akin to collaborating with an academic lab in which a lead investigator and graduate and post-doctoral students are all committed to making the process work.
Our absolute dedication to our customers at Sino Biological and the motivation for teams to stay up until late in the night is driven by our mission to advance life science and improve human health. Even though the company has grown significantly since its founding, it still functions like a small, very well-aligned and well-run machine. We all wear different hats and work closely together to get customers exactly what they want. Our high level of quality and extensive experience, combined with great flexibility and a true commitment to our customers, gives Sino Biological a measurable competitive advantage.
Going forward, there are additional steps that Sino Biological will be taking to build on our capabilities and ensure that we continue to provide the service and support that customers will need well into the future. One of those areas will be the establishment of a platform for antibody characterization to expand our one-stop-shop capacity. Today, we offer services from gene synthesis to expression to purification to QC, but we want to increase our QC capabilities. Additions will include a cell-based assay platform and a screening platform that will enable evaluation of more pharmaceutical aspects of antibodies, which will enable us to provide more of the information that clients are looking for.
To meet growing demand for our custom services, we are also investing heavily in our research and development capabilities. Sino Biological recently announced the launch of new R&D centers in Taizhou and Suzhou, China. We also have plans to increase our warehousing capacity in Frankfurt, Germany, and Pennsylvania in order to be able to stock larger quantities of catalog products at these sites and provide overnight shipping to Europe and North America.
We are also looking to acquire new companies via acquisition and are currently strategically evaluating various candidates. In addition to gaining access to new cutting-edge technologies, these acquisitions will give Sino Biological an even larger global physical footprint. Both will help us further grow our portfolio of antibodies and other bioreagents and our custom research, development, and manufacturing capabilities.
Dr. Amy Sheng is the head of CRO Program at Sino Biological. Amy joined Sino Biological’s North America Contract Research Organization team in 2021. She has a Ph.D. in molecular and cell biology from the Georgia Institute of Technology and is an ASCP-certified molecular biologist and an ASQ-certified CSSGB.
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