2023-06-28-世界卫生组织-INN_Proposed_List_129_-COVID-_6页_470kb

Summary of Proposed International Nonproprietary Names: List 129 - COVID-19 (Special Edition)

Core Content

This document outlines the proposed International Nonproprietary Names (INNs) for new active substances related to COVID-19 vaccines, specifically mRNA-based vaccines and recombinant spike proteins. The list is part of the World Health Organization (WHO) INN Programme, which aims to provide a unique, globally recognized name for medicinal products. The special edition of List 129 is a response to the exceptional circumstances of the pandemic and is open for public consultation for only two weeks, instead of the usual four months.

The proposed names are in Latin, English, and French (with some Spanish translations), and are intended for use in the naming of active substances in mRNA vaccines and recombinant proteins. These names are subject to public comments or formal objections within the specified timeframe.

Key Information

• Publication Date: 30 June 2023
• Consultation Period: 14 July 2023 (two weeks from publication)
• Special Edition Context: Due to the pandemic, the consultation period is shortened to two weeks.
• Electronic Structure: Available on MedNet at https://extranet.who.int/soinn/.
• Procedure Reference: "INN for Variant COVID-19 Vaccine Active Substances" can be found at https://www.who.int/publications/i/item/inn-21-520.

Proposed INNs

1. andusomeranum

• Chemical Description: mRNA, 5' capped, encoding a full-length, codon-optimized pre-fusion stabilized conformation variant (K982P and V983P) of the SARS-CoV-2 spike (S) glycoprotein (Omicron variant XBB.1.5), with two additional stop codons, flanked by an artificial 5' and 3' UTR derived from the human alpha globin gene (HBA1), modified to include an IDR sequence, and terminated by a 3' polyadenylation tail.
• Molecular Formula: Not explicitly provided.
• CAS Registry Number: 2918977-08-7
• Use: Immunological agent for active immunization (anti-SARS-CoV-2)

2. pitozinameranum

• Chemical Description: mRNA, 5' capped, encoding a full-length, codon-optimized pre-fusion stabilized conformation variant (K982P and V983P) of the SARS-CoV-2 spike (S) glycoprotein (Omicron sub-lineage XBB.1.16), flanked by 5' and 3' UTRs and a 3' polyadenylation tail.
• Molecular Formula: Not explicitly provided.
• CAS Registry Number: 2920299-36-9
• Use: Immunological agent for active immunization (anti-SARS-CoV-2)

3. raxtozinameranum

• Chemical Description: Similar to pitozinameranum, but with a different CAS registry number and UTR origin.
• Molecular Formula: Not explicitly provided.
• CAS Registry Number: 2887554-49-4
• Use: Immunological agent for active immunization (anti-SARS-CoV-2)

4. tegrenmeranum

• Chemical Description: mRNA, 5' capped, encoding the codon-optimized receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) glycoprotein (Omicron sub-lineages BA.4 and BA.5), with specific amino acid substitutions (R664 > Q, R665 > Q, R667 > Q, K968 > P, V969 > P), expressed as a fusion protein with the S glycoprotein signal peptide, and flanked by UTRs from the human beta globin gene.
• Molecular Formula: Not explicitly provided.
• CAS Registry Number: 2889466-36-6
• Use: Immunological agent for active immunization (anti-SARS-CoV-2)

5. upalsecovateinum

• Chemical Description: SARS-CoV-2 Omicron lineage B.1.1.529.5 (BA.5) spike glycoprotein (1-1255), stable pre-fusion conformation variant, trimer, produced in Spodoptera frugiperda (Sf9) insect cells, glycoform alpha.
• Molecular Formula: Not explicitly provided.
• CAS Registry Number: 2918783-99-8
• Use: Immunological agent for active immunization (anti-SARS-CoV-2)

6. vintesomeranum

• Chemical Description: mRNA, 5' capped, encoding a full-length, codon-optimized pre-fusion stabilized conformation variant (K982P and V983P) of the SARS-CoV-2 spike (S) glycoprotein (Omicron variant XBB.1.16), with two additional stop codons, flanked by an artificial 5' UTR and a 3' UTR derived from the human alpha globin gene (HBA1), modified to include an IDR sequence, and terminated by a 3' polyadenylation tail.
• Molecular Formula: Not explicitly provided.
• CAS Registry Number: 2923391-66-4
• Use: Immunological agent for active immunization (anti-SARS-CoV-2)

Additional Details

• Monomer Sequences: Provided in a table with sequences in Latin, English, and Spanish.
• Mutations:
  • R664 > Q, R665 > Q, R667 > Q, K968 > P, V969 > P (specific to tegrenmeranum).
• Post-translational Modifications:
  • Disulfide Bonds: Intra-chain positions are listed.
  • N-glycosylation Sites: N45, N56, N104, N131, N147, N216, N264, N313, N325, N585, N598, N639, N691, N699, N783, N1056, N1080, N1116, N1140, N1155, N1176.
  • O-glycosylation Sites: Experimentally confirmed with uncertainty on specific residues.

Main Points

• The proposed INNs are for mRNA-based vaccines and recombinant spike proteins targeting SARS-CoV-2.
• The special edition allows for shortened public consultation due to the pandemic context.
• The names are intended to ensure global standardization and clear communication of vaccine components.
• The mRNA vaccines use modified nucleosides such as N1-methylpseudouridine and 5-methyluridine or 5-methylcytidine.
• The spike proteins are pre-fusion stabilized and codon-optimized to enhance vaccine efficacy.
• The procedure for assigning INNs to variant vaccines is publicly accessible via the WHO website.