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Breakthrough on Novel Features of Omicron and An Anti-Omicron Antibody

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SHANGHAI, Jan. 4, 2022 — Joint research results from Biologics of Jemincare and Shanghai Institute of Materia Medica (SIMM) of Chinese Academy of Sciences (CAS) confirmed that JMB2002, an anti-SARS-CoV-2 neutralizing antibody (NAb) discovered by Biologics of Jemincare is still effective against Omicron variant of SARS-CoV-2.

A team of scientists led by Dr Su-Jun Deng from biologics of Jemincare R&D Center, and another team of scientists from SIMM of CAS, led by Professor H. Eric Xu and Dr Wanchao Yin, not only confirmed the binding and pseudovirus neutralization activity of JMB2002 against Omicron variant but also solved the structures of Omicron spike protein in complex with ACE2 and JMB2002 respectively (Figure 1 and Figure 2).

Joint research efforts revealed the mechanisms of increased infectivity and immune escape of the Omicron variant at the molecular level and demonstrated the unique binding mechanism of JMB2002 differing from all reported NAbs. Detailed findings of novel features of the Omicron variant and JMB2002 have been published on bioRxiv preprint website (Reference 1).

Figure 1. Structure of complex of SARS-CoV-2 Omicron variant spike protein RBD bound to ACE2. A. Overall structure and conformation of ACE2-RBD complex. B. RBD-ACE2 interaction interface. C. The interaction interface of RBD dimer.

Structure of complex of SARS-CoV-2 Omicron variant spike protein RBD bound to ACE2. A. Overall structure and conformation of ACE2-RBD complex. B. RBD-ACE2 interaction interface. C. The interaction interface of RBD dimer.

The latest research results indicated that JMB2002 had high binding activity to the Omicron variant and showed a potent Omicron pseudovirus neutralization function (Figure 2A, 2B).

It is encouraging considering that most approved and clinical-stage SARS-CoV-2 neutralizing antibody drugs have lost their neutralization activity or have shown significantly reduced neutralizing potency due to multiple mutations of the spike protein in Omicron variant.

One reason for the enhanced infectivity of Omicron variant is that its spike protein RBD (Receptor Binding Domain) has a higher binding ability to the SARS-CoV-2 receptor ACE2 than that of wild type. There are immediate needs for developing specific therapeutic antibodies targeting Omicron variant.

Scientists from Jemincare found that the binding affinity of JMB2002 Fab to the spike protein of Omicron variant is 4-fold higher than that of WT (Figure 2A). More importantly, professor H. Eric Xu’s group has solved the structure of the complex of Omicron spike trimer bound to JMB2002 (Figure 2C), the structure shows JMB2002 binds to the back of RBD, a unique binding epitope with novel conformation (Figure 2D).

It suggests that JMB2002 is a new class of SARS-CoV-2 neutralizing antibody with a binding mechanism different from all reported NAbs, classifying as class V NAb.

The results from the pseudovirus neutralization assay indicate that JMB2002 is a broad-spectrum neutralizing antibody targeting all WHO VOC except the Delta variant (Reference 1).

Figure 2. A. Binding of JMB2002 Fab to spike protein of Omicron and WT respectively. B. Neutralizing bioactivities to WT and Omicron variant by JMB2002 in pseudovirus neutralization assay. C. The comparison of the complex of Omicron Spike protein RBD bound to JMB2002 and ACE2. D. Novel binding epitope to Omicron Spike protein by JMB2002, classified as class V neutralizing Ab (NAb).

Figure 2. A. Binding of JMB2002 Fab to spike protein of Omicron and WT respectively. B. Neutralizing bioactivities to WT and Omicron variant by JMB2002 in the pseudovirus neutralization assay. C. The comparison of the complex of Omicron Spike protein RBD bound to JMB2002 and ACE2. D. Novel binding epitope to Omicron Spike protein by JMB2002, classified as class V neutralizing Ab (NAb).JMB2002 has finished phase Iclinical trial in ChinaIn June 2021, JMB2002 has finished Phase I clinical trial in healthy donors in China with excellent safety and desirable PK properties. In March 2021, JMB2002 has been approved for a clinical trial in the US (IND 154745).

At present, Jemincare produced enough JMB2002 drug substance for further clinical investigation at the 2000L bioreactor scale.

PRNewswire

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