ArticlePloS one2013
Identification and multidimensional optimization of an asymmetric bispecific IgG antibody mimicking the function of factor VIII cofactor activity.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 161 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
161 citing papers in PubMed, 1 synthesis or guideline pooled it, 318 citations in OpenAlex.
- Outcomes of Emicizumab in Acquired Hemophilia Patients: A Systematic Review.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/HemostasisPooled it
- Final Analysis Results from the AGEHA Study: Emicizumab Prophylaxis for Acquired Hemophilia A with or without Immunosuppressive Therapy.Thrombosis and haemostasis · 2025Trial
- Trial
- Pharmacokinetics and Pharmacodynamics of Emicizumab in Persons with Hemophilia A with Factor VIII Inhibitors: HAVEN 1 Study.Thrombosis and haemostasis · 2021Trial
- Evaluation of the Pharmacokinetics, Pharmacodynamics, and Safety of a Single Dose of Emicizumab in Healthy Chinese Subjects.Clinical pharmacology in drug development · 2021Trial
- Relative and Absolute Bioavailability Study of Emicizumab to Bridge Drug Products and Subcutaneous Injection Sites in Healthy Volunteers.Clinical pharmacology in drug development · 2019Trial
- A Pharmacometric Approach to Substitute for a Conventional Dose-Finding Study in Rare Diseases: Example of Phase III Dose Selection for Emicizumab in Hemophilia A.Clinical pharmacokinetics · 2018Trial
- Trial
- A bispecific antibody targeting conserved hemagglutinin epitopes confers broad protection against H7 avian influenza and accelerates viral clearance via localized respiratory delivery.Emerging microbes & infections · 2026Article
- Cost-effectiveness analysis of emicizumab use in hospitalized older individuals with acquired hemophilia A.Blood vessels, thrombosis & hemostasis · 2026Article
- Discovery and development of a bispecific antibody for the treatment of hemophilia.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Kunihiro Hattori, Tomoyuki Igawa, and Takehisa Kitazawa share Lasker Award honors for revolutionary hemophilia A therapy.The Journal of clinical investigation · 2026Article
- Bispecific antibodies for cancer therapy: evolution of structural formats and co-targeting strategies from wet-lab to AI-driven in silico modeling.Cancer letters · 2026Review
- Plasma emicizumab concentrations and bleeding rates in children and adults with severe hemophilia A.Research and practice in thrombosis and haemostasis · 2026Observational
- A Jehovah's Witness with Acquired Hemophilia A Who Successfully Avoided Blood Transfusions by Receiving Emicizumab.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2026Article
- Emicizumab enhances the ex vivo coagulant potential in plasma samples from patients with von Willebrand disease.International journal of hematology · 2026Article
- Emerging Role of Bispecific Antibodies in Precision Medicine, Cancer and Modern Therapeutics.Current oncology reports · 2026Review
- Next-generation FVIIIa-mimetic bispecific antibody NXT007: evaluation in preclinical models of hemostasis and thrombosis.Blood advances · 2026Article
- Review: application and opportunities for machine learning and artificial intelligence in preclinical immunogenicity risk assessment.Frontiers in immunology · 2026Review
- Systematic Production of IgG-Like Bispecific Antibodies via Intein-Mediated Protein Trans-Splicing.Methods in molecular biology (Clifton, N.J.) · 2026Article
101 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
19 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In hemophilia A, routine prophylaxis with exogenous factor VIII (FVIII) requires frequent intravenous injections and can lead to the development of anti-FVIII alloantibodies (FVIII inhibitors). To overcome these drawbacks, we screened asymmetric bispecific IgG antibodies to factor IXa (FIXa) and factor X (FX), mimicking the FVIII cofactor function. Since the therapeutic potential of the lead bispecific antibody was marginal, FVIII-mimetic activity was improved by modifying its binding properties to FIXa and FX, and the pharmacokinetics was improved by engineering the charge properties of the variable region. Difficulties in manufacturing the bispecific antibody were overcome by identifying a common light chain for the anti-FIXa and anti-FX heavy chains through framework/complementarity determining region shuffling, and by pI engineering of the two heavy chains to facilitate ion exchange chromatographic purification of the bispecific antibody from the mixture of byproducts. Engineering to overcome low solubility and deamidation was also performed. The multidimensionally optimized bispecific antibody hBS910 exhibited potent FVIII-mimetic activity in human FVIII-deficient plasma, and had a half-life of 3 weeks and high subcutaneous bioavailability in cynomolgus monkeys. Importantly, the activity of hBS910 was not affected by FVIII inhibitors, while anti-hBS910 antibodies did not inhibit FVIII activity, allowing the use of hBS910 without considering the development or presence of FVIII inhibitors. Furthermore, hBS910 could be purified on a large manufacturing scale and formulated into a subcutaneously injectable liquid formulation for clinical use. These features of hBS910 enable routine prophylaxis by subcutaneous delivery at a long dosing interval without considering the development or presence of FVIII inhibitors. We expect that hBS910 (investigational drug name: ACE910) will provide significant benefit for severe hemophilia A patients.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.