1. Introduction to the Project

1.1 Introduction to technical achievements

The project developed a technical method for rapid screening and preparation of specific monoclonal antibodies against BK virus based on whole human CA mouse combined with single-cell sequencing technology. This technology utilizes in-vitro cultivation, purification, and self-assembly of BK virus capsid protein (BK-VLP) to immunize all human CA mice. Through a specific immune cycle, the mice are stimulated to produce a large number of B cells secreting specific antibodies; Through FACS screening of specific fluorescent antigens and antibodies, a large number of target B cells were obtained, and then subjected to GEX sequencing + VDJ sequencing combined analysis and high-throughput screening according to specific standards to obtain the target antibody sequence. Then, the target antibody is obtained through in vitro expression and purification. The antibody affinity is detected by ELISA and a pseudovirus attack protection test is performed to verify the specificity and effectiveness of the obtained antibody. Finally, one or several specific human monoclonal antibodies against BK virus are obtained.

1.2 Technical analysis and advantages

The commonly used anti-BK infection method today is still to reduce immune suppression and restore the immune function of patients. However, this method can easily lead to immune rejection, and the consequences are difficult to control; Antiviral drugs are a clinical auxiliary measure second only to immunosuppressants, and these drugs do have the effect of reducing virus titers and controlling infection progression in vitro experiments; but with low bioavailability and significant toxic side effects in the human body, it is not the best treatment. IVIG (immunoglobulin intravenous injection) therapy has the advantages of mild intensity, good specificity, and significant effects, but its cost is high and there is an abnormal increase in viral load; the adoptive T cell therapy is currently an emerging hot treatment method, but it is expensive and can result in many uncontrollable outcomes when injected back into the patient's body. Therefore, there is currently no specific therapy for BK virus infection both domestically and internationally, posing a serious threat to human health.

This project has one invention patent for a Raman homogeneous non diagnostic detection method that utilizes antibodies to recognize binding antigens. This technology has a solid foundation in preliminary experiments, as well as laboratory conditions and related experimental facilities for industrial commercialization. Unlike its competitors, this technology not only has high-throughput and rapid screening functions, but also can obtain a large number of target B cells that can secrete specific antibodies from all human CA mice, and further obtain one or more specific IgG1 antibodies against the BK virus. The developed specific antibodies have a high specific protective effect, breaking through the clinical lack of efficiency or gentleness, it can be used for the barrier for treatment for immune compromised patients to resist BK virus infection.

1.3 Main products and applications of technical achievements

Specific anti BK viremia monoclonal antibodies can be used to prevent and treat BK virus infection with specific anti BK virus monoclonal antibody drugs.

(1) Preventing BK virus related kidney disease in kidney transplant recipients: Typically, within the first three months after transplantation, about 30% -40% of patients will experience BK virus urine, and 10% -20% of patients will experience BK viremia; within one year after transplantation, approximately 1-10% of kidney transplant recipients will develop BK virus related kidney disease, ultimately resulting in graft dysfunction or graft loss. Currently, immunosuppressive therapy is commonly used in clinical practice for self-recovery, but it can easily trigger immune rejection reactions; therefore, in the process of immunosuppressive therapy after kidney transplantation surgery, prophylactic use of BK monoclonal antibodies can prevent the occurrence of BK virus reinfection while avoiding immune rejection reactions;

(2) Preventing hemorrhagic cystitis in bone marrow transplant patients: About 10% -12% of transplant recipients are prone to developing hemorrhagic cystitis within 6 months after transplantation, with varying degrees of severity, often manifested as BK viruria and painful hematuria. Severe cases may even require blood transfusion, clot removal treatment, and in some cases may even lead to death; therefore, prophylactic use of BK monoclonal antibodies after bone marrow transplantation can eliminate potential BK viruses in the body and prevent the occurrence of hemorrhagic cystitis;

(3) Treatment of BK virus infection in HIV patients: HIV patients have weakened immune system and physical constitution, making them susceptible to BK virus infection. Research surveys have shown that about 74% of HIV infected individuals have BK virus infection in multiple tissues, which often leads to salivary gland related complications and neurological diseases such as meningitis and/or meningoencephalitis. Therefore, BK virus monoclonal antibodies can be used to treat BK virus infection in HIV patients after infection. Conventional chemical drugs (such as cetuximab, leflunomide, or quinolone) have unstable therapeutic effects and significant side effects, which can easily cause secondary harm to HIV patients. However, the use of monoclonal antibodies not only has strong targeting and significant therapeutic effects, but also has extremely low toxic side effects on patients;

(4) Preventing tumor diseases induced by BK virus: BK virus is also considered a potential or auxiliary factor in tumor occurrence. BK virus has been dormant in human urinary tract cells, and is considered to be the potential cause of urinary system tumors, such as prostate cancer and bladder cancer; in addition, the persistent presence of BK virus in the central nervous system after infection will increase the incidence rate of head and neck tumors. Therefore, monoclonal antibody drugs against BK virus can be used to eliminate the potential BK virus in the body and prevent the occurrence of related cancer diseases.

1.4 Technical achievement commercialization stage

The project has completed the small-scale process of preparing BK VLP capsid protein antigen, screening, expression, and purification of antibody proteins, and is currently conducting pilot-scale commercialization experiments.

1.5 Technical team

The technical team of this project is the Modern Biology Research Group of the School of Pharmacy, Jilin University. In recent years, the team has mainly engaged in drug research and development, and has carried out a series of work in the field of drug screening using Raman spectroscopy technology. In the past five years, one of the developed varieties has been approved for clinical trials by the US FDA and one has been approved for clinical trials by the Chinese CDE.

The head of the research group is deeply involved in the interdisciplinary application fields of spectroscopy technology, drug development, and cell biology, and has collaborated with relevant professors from the School of Chemistry, Jilin University. The multidisciplinary research team is very stable. More than ten Chinese invention patents and one utility model patent have been authorized. He has hosted 1 National Natural Science Foundation project, 1 National Natural Science Foundation Youth Fund project, and 3 Jilin Provincial Department of Science and Technology projects. He has received the Second Prize of Jilin Province Science and Technology Progress Award.

2. Market Potential Analysis

BK virus has an infection rate of 80% -90% in the population, and is suppressed by the normal immune defense mechanism of the human body. After infection, BK virus will be in a “dormant” state in the cells of urinary organs such as the ureter. If the human body undergoes long-term immunosuppressive treatment, it will cause a significant decline in the body’s immune function, and the dormant BK virus will “make a comeback”.

The current various clinical therapies for anti BK virus have high toxic side effects and are not suitable for clinical use in immunocompromised patients. Antibody therapy alone has attracted a large number of industry professionals and unprecedented market demand due to its high specificity and extremely low side effects. However, currently, there are only two known antibody drugs developed by Novartis and the University of Zurich that are known to be used for clinical anti BK virus infections and have not been marketed, The development of antibodies against BK virus infection both domestically and internationally is currently in its infancy, with great research and development space and market potential waiting to be explored. According to statistics, the world market size of BK virus monoclonal antibody drugs in 2025 (estimated launch time of Novatis products), 2026, and 2027 corresponds to a total of 7 billion US dollars, 10.5 billion US dollars, and 14.8 billion US dollars, respectively. The market share has been increasing year by year, and the market prospects are becoming increasingly broad.

Nowadays, many foreign companies such as Boehringer Ingelheim, Johnson & Johnson, Pfizer, and Merk have begun to seize the lead in the antibody drug market, and have formulated their own market positioning and strategies, invested heavily in marketing funds and technological research and development. At present, the development of antibody drugs for viral therapy worldwide is still in its early stages, and the market has not yet opened up. Antibody drugs with therapeutic efficacy and potential for use in human treatment are only the MAU868 antibody protein developed by Novartis, which has entered clinical phase III. It is not difficult to predict that its subsequent market investment will increase year by year. Therefore, seizing the antibody market for treating BK virus infection will undoubtedly bring huge market profits.

3. Financing Needs and Financing Purposes

The project is planned to raise 30 million yuan, with the funds mainly used for antibody development. It will jointly apply for IND for the development of this pipeline; It will enter the industrial park, carry out industrialization, and achieve the goal of achievement commercialization.

4. Analysis of Technical Achievements and Benefits

4.1 Economic benefits

The currently popular monoclonal antibody drugs, such as Adalimumab, are used to treat rheumatoid arthritis and ankylosing spondylitis. In 2021, the market size of Adalimumab in China was approximately 1.6 billion yuan, a year-on-year increase of 45.5%. The sales revenue in the Chinese market in 2022 reached 4.15 billion yuan, and it is expected to have reached 24.01 billion yuan by 2030; in 2021, the global market size of Adalimumab exceeded 152.4 billion yuan. In 2022, the global sales exceeded 20 billion US dollars, and it is expected to have reached 262.4 billion yuan by 2028. The average market price of BK virus monoclonal antibody after its launch is about 2000 yuan/piece; the minimum preventive dose for each patient is an average of 2 doses per month, including preventive treatment for BK virus induced cancer. The antibody dosage can be adjusted based on different levels of BK virus incubation in the body and individual factors. The antibody dosage for treating BK virus infection in HIV patients can be doubled. Based on this, it is estimated that the annual market share of BK virus monoclonal antibody drugs will reach billions of yuan within three years after initial approval for marketing, Conservatively, it is estimated that the growth rate will increase by 30% -40% year by year, and the market share will gradually climb above the 20 billion yuan mark within five years.

4.2 Social benefits

The construction of the project conforms to industrial policies, helps to build a healthy China, increases people’s well-being, and becomes a driving force for economic growth. After project operation, it can increase the local fiscal revenue and play a positive role in promoting the regional economic growth.

5. Contact Method

Contact person: Xu Wan

Tel: 13756652164