Antibody Engineering Capability
Harbour Mice® transgenic mice platforms (H2L2 and HCAb) enable the generation of fully human antibodies with excellent developability for therapeutic applications. Additionally, in certain scenarios, protein engineering is required to modify molecules to acquire new properties or create innovative modalities.
Our scientific team has accumulated extensive experience in protein engineering and commits to use state-of-the-art techniques to deliver the best biologics. We leverage powerful surface display technologies to capture millions of molecular variants and employ structural biology and molecular dynamics to capture atomic changes.
Beacon® can support the separation and screening of 10,000+ cells in a single run with one 14K or 20K OptoSelect chip. Enriched plasma cells are individually loaded into NanoPen chambers on the chip. Our proprietary medium preserves the viability and facilitates antibody secretion of these plasma cells. Multiple in-chip assays can be sequentially performed to screen those plasma cells, and the cells with desired signals wll beare selected and exported one by one through OEP technology. The entire workflow is completed in just one day.
Each 20K OptoSelect chip has 20,000 individual NanoPen chambers and can separate and screen up to 20,000 cells within a single run.
With real-time fluorescent microscopy technology, different assays could be performed in-chip for plasma cell screening, including:
All these advantages make SBC platform to become highly efficient and robust antibody discovery platform.
Opto-electro positioning (OEP) technology precisely manipulates and unloads cells to 96-well plates preloaded with single-cell sequencing reagents.
We have established both phage display and yeast display technology platforms to meet various applications of directed evolution for protein engineering. These platforms facilitate the discovery of antibodies from immunized animals, human PBMCs or other sources , and facilitate tasks such as affinity maturation, PTM removal, cross-reactivity optimization, and improvement of biophysical properties.
Both phage display and yeast display technologies are suitable for multiple different applications, however, each technology has its own advantages in specific scenarios. Our scientific team selects the most suitable technology based on the nature of the molecule.
Affinity maturation stands as a crucial and widely employed application of surface display technologies in the field of antibody engineering. By combining yeast display technology with streamlined processes for FACS sorting and antibody screening, the workflow of affinity maturation has been significantly shortened, enabling the rapid generation of candidates with enhanced binding activities.
The figure below illustrates the workflow for improving the binding affinity of an HCAb molecule using the yeast display technology platform. Using an anti-PD-1 HCAb as an example,the monomeric VH domain with proper tags (e.g., His-tag) was displayed on the yeast cell surface. Mutagenic libraries were created for each CDR region using degenerated primers, which covered the potential antigen binding sites within the three CDRs. These libraries were subject to MACS sorting and sequential multiple rounds of FACS sorting by proper forms of antigens to isolate the population of yeast cells with increased binding activities. After analyzing the VH sequences of the variants from different mutagenic libraries, the “hotspot” mutations which make critical impacts on antigen binding were identified. The binding activities of the variants from each CDR mutagenic library can be ranked by FACS or Octet. The “hotspot” mutations from each CDR were then combined into a new mutagenic library to include the combinatorial mutagenesis across different CDRs. The new library was subjected to new round of FACS sorting and screening, and the new variants carrying multiple mutations with significantly increased binding activities can be retrieved.
As depicted in the figures below, VH mutants derived from Anti-PD1 parental HCAb exhibit much stronger binding activities to human PD-1 on CHO-K1 cells. Consequently, these mutants also demonstrated significantly improved activities to inhibit PD-1/PD-L1 signaling in the reporter gene assay.
With our expertise in structural and computational biology, we have the capability to design and optimize novel antibodies and other protein modalities to possess required properties such as excellent binding affinity, solubility or stability. This approach offers a faster and more cost-efficient way to generate superior biologics.
In the example below, our scientists developed a generalized approach to create “super-stable” HCAb. By introducing an additional intra-domain disulfide bond into the buried core of beta-sheets in the VH domain, a significant improvement in the thermal stability (Tm) of the antibody was achieved while other properties are kept unchanged. One of the designed variants, with the additional disulfide bond, exhibited a Tm of the VH domain-only format reaching nearly 75°C, demonstrating exceptional heat resistance.
We are building a new paradigm of antibody discovery by taking advantage of artificial intelligence and high throughput screening technologies. hyperSCREEN is a newly developed novel platform to leverage next-generation sequencing and machine learning to screen millions of sequences and enables us to identify rare sequences that are usually missed by conventional screening methods.
In one example, a panel of HCAbs specific to a novel target were identified by Beacon SBC that showed good bind activities to target cells. In parallel, another panel of HCAbs with good binding activities were identified by hyperSCREEN. Sequence analysis for the HCAbs from the two platforms showed good sequence diversity: 10 HCAbs from the two platforms were categorized into 3 clusters; each platform discovered a unique cluster containing multiple sequences, while both platforms also discovered similar overlapping sequences belonging to the same cluster. This example demonstrates the power of combining high throughput screening and artificial intelligence in antibody discovery.
Beacon® single B cell screening
Display technology
CAR-function based functional screening
Hybridoma
HCAb direct cloning screening
TCR Mimic Antibody
Functional characterization
Binding / Affinity
Antibody production
In vitro functional assay
Developability
Protein
Cell line
DNA
mRNA
Target assessment
Recombinant protein
Recombinant cell-line
Affinity maturation ▶
Humanization▶
Fc-Engineering▶
Structure-Based Protein Design
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Stable cell line
Process development
Manufacture
PK / PD
Efficacy
ADA
TOX
Dr. Jingsong Wang is Chairman of Nona Biosciences. Prior to that, Dr. Wang served as Head of China R&D and Head of Translational Medicine, Asia Pacific, at Sanofi. He is a former attending physician and clinical fellow at Harvard Medical School. Dr. Wang received his Ph.D. in Molecular Pharmacology from China Pharmaceutical University and has also completed a Molecular Immunology Research Fellowship at Dr. Laurie Glimcher’s laboratory at the Harvard School of Public Health.
Dr. Yiping Rong is our Chief Scientific Officer. He is a well-recognized scientist with about 20 years’ experience of biomedical research and drug discovery. Dr. Rong used to work at Sanofi, JNJ and Roche and built strong expertise in cancer biology and pharmacology. He led and contributed to >15 programs entering clinical trials. He is also involved in translational research work for a few drugs. Multiple mAb or bispecific antibodies generated from his team were out licensed to MNCs. Some highly innovative first-in-class projects are in clinical trials. He worked on apoptosis, epigenetics, immuno-oncology, and cancer cell signaling fields and led the drug discovery projects including kinase, enzyme, receptor/ligand, protein-protein-interaction targets by small molecules or monoclonal antibodies. Dr. Rong received his Ph.D. degree in Pharmacology from Case Western Reserve University (Cleveland, Ohio). He is the member of American Association of Cancer Research and has more than twenty publications in cancer research field, including Nature Genetics, Molecular Cell, PNAS papers. He is also the inventor of dozens of patents in drug discovery field.
Dr. Jiyong Zhang leads business development at Nona Biosciences, bringing vision and dedication to strategic growth and client satisfaction. With 15 years of experience in biotherapeutic research and development, Dr. Zhang’s understanding of market dynamics and ability to identify mission-aligned opportunities are evident.
Before overseeing business development at Nona, Dr. Zhang played key roles at Alexion and Abbvie, contributing to antibody discovery, engineering, and bispecific antibody R&D. His scientific experiences and knowledge in biotherapeutic innovation makes him a forward-thinking strategist focused on enhancing service offerings to meet evolving client needs.
With Dr. Zhang and his team driving business development, Nona Biosciences is poised to offer innovative solutions and unparalleled service. This solidifies the company’s position as a trusted and client-focused drug discovery partner in the dynamic landscape of biotherapeutic innovation.
Dr. Joe Zhao is Vice President and Head of External Innovation of Nona Biosciences. Joe holds a BS from Fudan University and a PhD from University of Delaware, followed by postdoctoral trainings at Lankenau Medical Center and Zeneca Pharmaceuticals. Prior to joining Harbour BioMed, he was in small biotechs (Pharmacopeia and Ligand Pharmaceuticals) and large MNC (BMS). Joe has 25 years of combined experience in drug discovery of both small molecules and biologics in therapeutic areas of immuno-oncology, immunology, and genetic diseases.
Mr. Louis Liu is Senior Vice President and Head of Scientific Operation of Nona Biosciences. He graduated from Bethune Medical University with Bachelor Degree of Medicine. He has over 30 years’ experience in antibody technology platform establishment, antibody discovery and discovery team management experience. Previously he worked in Syntron Bioresearch Inc as R&D manager, Strategic Diagnostic Inc as product development supervisor, Rockland Immunochemical Inc as Manager of Monoclonal Antibody service and product development, GenScript Ltd as vice president of Antibody Division, Shanghai ChemPartner as vice president of Biologics Discovery.
Dr. Yun He is Chief Technology Officer of Nona Biosciences. Before Nona Biosciences spun off from Harbour BioMed, Dr. He served as Head of Antibody Technology at Harbour BioMed. During his tenure there, Dr. He contributed to multiple discovery programs and led the team in establishing HBICE® platform. Prior to joining Harbour BioMed, Dr. He was an Investigator at Biologics Center in Novartis, where he was responsible for antibody engineering and bioinformatics. Prior to that, Dr. He was the group leader of Bioinformatics at GenScript. Dr. He received his Ph.D. from the Chinese Academy of Sciences, with a focus on molecular biology and bioinformatics.
Dr. Musheng Bao earned his Ph.D. in China and completed his postdoctoral training at MD Anderson Cancer Center and Baylor Institute for Immunology Research. Beginning his professional journey as a Scientist II at MedImmune, Dr. Bao later transitioned to Sanofi, where he served as a Principal Scientist. Following this, he joined Harbour BioMed, where he led a team dedicated to therapeutic antibody development utilizing the Harbour Mice® platform. Presently, Dr. Bao has taken on the role of Head of Biology at Nona Biosciences.
Dr. Arkinstall has demonstrated remarkable competence throughout his career. He is a respected leader in drug discovery with substantial roles under his belt, including Research Head, Chief Scientific Officer (CSO), and Chief Executive Officer (CEO) positions at various pharmaceutical or biotech companies. Dr. Arkinstall served as CEO of Elstar Therapeutics and Revitope Oncology, companies advancing novel classes of multi-specific antibody-based cancer drugs. He previously was also the CSO of Kymab, an antibody therapeutics company founded in Cambridge, UK, prior to which he spent 16 years in progressively senior research leadership roles at EMD (Merck) Serono, and its associated entities across Europe and the United States.
Dr. Grosveld is Co-founder and CSO of Harbour Antibodies and the inventor of Harbour Mice®, Professor and former Head of Department of Cell Biology and Department of Clinical Genetics at Erasmus University Medical Center, Rotterdam, a fellow of Royal Society and a member of Royal Netherlands Academy of Arts and Sciences. Dr. Grosveld’s research on the control of globin gene expression has been selected as one of the top ten achievements of Medical Research Council (UK) (MRC) in the 20th century by Higher Education and Research Opportunities in the U.K. Dr. Grosveld was awarded the Louis-Jeantet Prize for Medicine in 1991, the Spinozapremie (Spinoza Prize) in 1995.
Dr. Kamen is a Venture Partner at Third Rock Ventures. In 2005, he co-founded BioAssets Development Corporation and served as its Chairman. He currently serves as an independent non-executive Director of Harbour BioMed and a director of Jounce Therapeutics (NASDAQ:JNCE). He was previously a director of Neon Therapeutics and Harbour Antibodies. Earlier in his career, he was senior vice president of scientific affairs at the pioneering biotechnology firm named Genetics Institute, Inc. Dr. Kamen received his bachelor’s degree in biophysics from Amherst College, a Ph.D. in biochemistry and molecular biology from Harvard University Graduate School of Arts and Sciences. During his academic scientific career, he worked at the Imperial Cancer Research Fund.
Dr. Kramer serves as CSO of Portage Biotech Inc. Dr. Kramer previously served as Vice President and Head of Discovery for Oncology Therapeutics at Janssen Research & Development, LLC (the Pharmaceutical Division of Johnson and Johnson), where he was responsible for leading Global Discovery, focusing on aberrant signaling cascades in tumor cells, as well as epigenetic reprogramming and tumor immunology using both small molecule and protein-based large molecule approaches. Prior to joining Janssen Research & Development, LLC, Dr. Kramer served as VP Drug Discovery and Research for Bristol-Myers Squibb (BMS), where he provided scientific leadership and strategic oversight for many pre-clinical Oncology and Immunology programs and projects that entered development. Dr. Kramer was previously an Assistant Professor at Harvard Medical School. Dr. Kramer received his Ph.D. in pharmacology from the University of Vermont and completed his post-doctoral fellowship in Oncology at the National Cancer Institute, National Institutes of Health.
Peter Moesta, Ph.D., oversaw the development, production and worldwide launch of important medicines, such as Humira, Yervoy and Opdivo. Dr. Moesta previously served in executive roles at Bristol-Myers Squibb.
Dr. Tian is an academician of Chinese Academy of Engineering, a member of Academia Europaea and a medical immunologist. Currently, he is a professor at University of Science and Technology of China (USTC), where he also works as Dean at School of Basic Medical Sciences, and Director at Institute of Immunology. He is also the Director of the Key Lab of Innate Immunity and Chronic Diseases of Chinese Academy of Science.
Dr. Tian was awarded with the National Science Fund for Distinguished Young Scholars. He is the academic leader of Chang Jiang Scholars Program as well as the Innovation Research Program of National Natural Science Foundation of China. Dr. Tian is Head of National Science and Technology Major Project and Chief Scientist of National Major Research Plan Program.
Dr. Tian’s laboratory is credited with seminal discoveries regarding basic knowledge and clinical study of natural killer (NK) cells, particularly liver-resident NK cells, cytokine-producing NK cells, and NK cell-based immunotherapy.
