ArticleScientific reports2017
Long lasting neutralization of C5 by SKY59, a novel recycling antibody, is a potential therapy for complement-mediated diseases.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 104 citations in OpenAlex.
- Efficacy and safety of crovalimab versus eculizumab in complement inhibitor-naïve patients with paroxysmal nocturnal hemoglobinuria: Chinese subgroup analysis of the phase 3 COMMODORE 2 study.Annals of hematology · 2026Trial
- Randomized phase I trial outcomes show safe and sustainable inhibition of classical and lectin complement pathways by empasiprubart.Nature communications · 2025Trial
- Patient-reported outcomes in patients with paroxysmal nocturnal hemoglobinuria treated with crovalimab and approved C5 inhibitors in the phase III COMMODORE 2 and 1 studies.Annals of hematology · 2025Trial
- Pharmacokinetic characterization and exposure-response relationship of crovalimab in the COMMODORE 1, 2 and 3 and COMPOSER trials of patients with paroxysmal nocturnal haemoglobinuria.British journal of clinical pharmacology · 2025Trial
- Safety of Crovalimab Versus Eculizumab in Patients With Paroxysmal Nocturnal Haemoglobinuria (PNH): Pooled Results From the Phase 3 COMMODORE Studies.European journal of haematology · 2025Trial
- Trial
- Mapping of C5-Blocking Monoclonal Antibodies Reveals New C5 Inhibitory Epitopes and Novel Modes of C5 Inhibition.Immunology · 2026Article
- Crovalimab Rescue Therapy in a Case With Genetic Complement Mediated Thrombotic Microangiopathy.Kidney medicine · 2026Article
- Beyond Terminal Blockade: A Mechanism-Based Approach to Complement Inhibitor Selection in Paroxysmal Nocturnal Hemoglobinuria.Drug design, development and therapy · 2026Review
- Treatment strategies for rituximab-resistant primary membranous nephropathy: from resistance mechanisms to emerging therapies.Frontiers in immunology · 2026Review
- Therapeutic Antibodies in Hematology: Advances in Malignant and Non-Malignant Disorders.Cells · 2025Review
- A Quantitative Approach to Guiding Target Antigen Selection and Antibody Optimization in Recycling Antibody Discovery.The AAPS journal · 2025Article
- Fifty years of monoclonals: the past, present and future of antibody therapeutics.Nature reviews. Immunology · 2025Article
- Structure and function of therapeutic antibodies approved by the US FDA in 2024.Antibody therapeutics · 2025Review
- Protein-Based Degraders: From Chemical Biology Tools to Neo-Therapeutics.Chemical reviews · 2025Review
- Exploring Potential Complement Modulation Strategies for Ischemia-Reperfusion Injury in Kidney Transplantation.Antioxidants (Basel, Switzerland) · 2025Review
- Managing transient immune complex reactions in patients with paroxysmal nocturnal hemoglobinuria: clinical observations from the COMMODORE 1 and 2 studies.Therapeutic advances in hematology · 2025Article
- Complement-targeted therapeutics: Are we there yet, or just getting started?European journal of immunology · 2024Review
- Genetic variants contribute to modulation of renal function in patients with immune thrombotic thrombocytopenic purpura.Blood vessels, thrombosis & hemostasis · 2024Article
- Beyond Recycling Antibodies: Crovalimab's Molecular Design Enables Four-Weekly Subcutaneous Injections for PNH Treatment.International journal of molecular sciences · 2024Article
10 more citing papers are in PubMed but not listed here.
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Authors and funding
34 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dysregulation of the complement system is linked to the pathogenesis of a variety of hematological disorders. Eculizumab, an anti-complement C5 monoclonal antibody, is the current standard of care for paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS). However, because of high levels of C5 in plasma, eculizumab has to be administered biweekly by intravenous infusion. By applying recycling technology through pH-dependent binding to C5, we generated a novel humanized antibody against C5, SKY59, which has long-lasting neutralization of C5. In cynomolgus monkeys, SKY59 suppressed C5 function and complement activity for a significantly longer duration compared to a conventional antibody. Furthermore, epitope mapping by X-ray crystal structure analysis showed that a histidine cluster located on C5 is crucial for the pH-dependent interaction with SKY59. This indicates that the recycling effect of SKY59 is driven by a novel mechanism of interaction with its antigen and is distinct from other known pH-dependent antibodies. Finally, SKY59 showed neutralizing effect on C5 variant p.Arg885His, while eculizumab does not inhibit complement activity in patients carrying this mutation. Collectively, these results suggest that SKY59 is a promising new anti-C5 agent for patients with PNH and other complement-mediated disorders.
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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.