2011-12-30-世界卫生组织-INN_Bio_Review_2012_65页_307kb

Summary of International Nonproprietary Names (INN) for Biological and Biotechnological Substances

Core Content

The World Health Organization (WHO) established the International Nonproprietary Name (INN) system to provide unique, non-proprietary names for medicinal substances, ensuring global recognition and standardization. This document reviews the current status and policies of INN assignment for biological and biotechnological substances, highlighting the structure and naming conventions developed over the years.

Main Viewpoints

• INN Purpose: INNs are unique, non-proprietary names assigned to medicinal substances to facilitate identification and communication. They are not tied to any commercial rights and are considered public property.

• Historical Context: Since the early days of the INN program, names have been assigned to various biological and biotechnological substances. In 1959, the first INNs for animal insulin preparations were introduced. By 1982, the INN "insulin human" was proposed for recombinant insulin, reflecting the growing complexity of biotech products.

• Naming Conventions: Specific letter groups, called stems, are used in the names of compounds related by structure or function to aid recognition. For example, -mab is used for monoclonal antibodies, -ase for enzymes, and -kin for interleukins.

• Greek Letters in Naming: Greek letters are used to denote differences in glycosylation patterns in recombinant glycosylated proteins, such as erythropoietin derivatives (-poetin) and coagulation factors (-cog).

• INN Schemes: Certain groups have established INN schemes, such as antisense oligonucleotides with the stem -ryn, gene therapy products using a two-word system, and monoclonal antibodies with a standardized naming format.

• Current Challenges: The increasing complexity and diversity of biological and biotechnological products present challenges in naming, particularly for new categories like peptide vaccines, transgenic products, and cell therapy products. The WHO continues to review and update these naming systems to ensure they remain relevant and useful.

Key Information

1. Pharmacological Classification

• Alimentary tract and metabolism: Insulins.
• Anti-infectives: Antimicrobial, bactericidal permeability increasing polypeptides.
• Antineoplastics: Peptide vaccines / recombinant vaccines, toxins.
• Blood and agents acting on the haemopoietic system: Antithrombins, blood coagulation cascade inhibitors, blood coagulation factors, erythropoietin type blood factors, heparin derivatives, hirudin derivatives, thrombomodulins.
• Immunomodulators and immunostimulants: Colony stimulating factors, interferons, interleukin receptor antagonists, interleukin type substances, monoclonal antibodies, receptor molecules.
• Hormones and related substances: Growth hormone derivatives, growth hormone antagonists, oxytocin derivatives, pituitary / placental glycoprotein hormones, pituitary hormone-release stimulating peptides, synthetic polypeptides with corticotropin-like action, vasoconstrictors, vasopressin derivatives.
• Various: Antisense oligonucleotides, enzymes, gene therapy products, growth factors, peptides and glycopeptides, skin substitutes, transgenic products, vaccines.

2. Current Status of Stems and Systems

2.1 Groups with respective stems

• Antisense oligonucleotides: -ryn
• Blood coagulation cascade inhibitors: -cogin
• Blood coagulation factors: -cog
• Colony stimulating factors: -stim
• Enzymes: -ase
• Erythropoietin type blood factors: -poetin
• Growth factors: -ermin
• Growth hormone derivatives: som-
• Heparin derivatives: -parin
• Hirudin derivatives: -irudin
• Pituitary hormone-release inhibiting peptides: -relix
• Interleukin receptor antagonists: -kinra
• Interleukin type substances: -kin
• Monoclonal antibodies: -mab
• Oxytocin derivatives: -tocin
• Peptides and glycopeptides: -tide
• Pituitary hormone-release stimulating peptides: -relin
• Receptor molecules: -cept
• Synthetic polypeptides with corticotropin-like action: -actide
• Vasoconstrictors, vasopressin derivatives: -pressin

2.2 Groups with respective pre-stems

• Aptamers: -apt-
• Antimicrobial, bactericidal permeability increasing polypeptides: -ganan
• Neurotrophins: -neurin

2.3 Groups with INN schemes

• Antithrombins
• Gene therapy products
• Insulins
• Interferons
• Pituitary / placental glycoprotein hormones

2.4 Groups without respective stems or INN schemes

• Growth hormone antagonists
• Thrombomodulins
• Toxins

3. General Policies

• Blood Products: INNs are not assigned to natural human blood products. Recombinant versions should have names reflecting established names. If activated, "activated" should be included.
• Fusion Proteins: INNs are assigned to some fusion proteins, and if a stem exists for either part, it should be included. The term "fusion" is not used in the name.
• Gene Therapy Products: A two-word system is used, with a prefix, infix, and suffix. Examples include -adeno- for adenovirus and -vec for vector.
• Glycosylated Compounds: Greek letters are used to denote differences in glycosylation. Prefixes are used for amino acid sequence differences.
• Immunoglobulins from Plasma: No INN is assigned due to the complexity of their nomenclature.
• Monoclonal Antibodies (mAbs): The naming format includes a prefix, a substem A (target class), a substem B (species origin), and a suffix. Examples: -mab, -b, -e, -o, -u, -xizu.
• Non-glycosylated Compounds: Use of stems and prefixes to indicate differences in amino acid sequences.
• Skin Substitutes: Considered engineered tissue, thus not included in the INN system.
• Transgenic Products: If an INN exists, the same name is used with qualification to indicate transgenic origin.
• Vaccines: Not included in the INN system. Names are assigned through recommendations and pharmacopoeial monographs. Peptide vaccines are more straightforward to name.
• Cell Therapy Products: A naming scheme is under development.

4. Summary of Assigned INNs

• Antimicrobial, bactericidal permeability increasing polypeptides: iseganan (85), omiganan (89), pexiganan (78)
• Antisense oligonucleotides: afovirsen (97), aganirsen (103), alicaforsen (97), anivamersen (105), aprinocarsen (97), beclanorsen (101), cenersen (97), custirsen (99), drisapersen (106), eteplirsen (103), fomivirsen (97), gataparsen (103), mipomersen (100), miravirsen (101), oblimersen (97), radavirsen (106), trabedesen (98), trecovirsen (97)
• Antithrombins: antithrombin III (60), antithrombin alfa (93), antithrombin gamma (107)
• Blood Coagulation Cascade Inhibitors: drotrecogin alfa (activated) (86), pegnivacogin (106), taneptacogin alfa (90), tifacogin (78)
• Blood Coagulation Factors:
  • Factor VII: -eptacog → eptacog alfa (77), eptacog alfa pegol (101), vatreptacog alfa (98)
  • Factor VIII: -octocog → beroctocog alfa (98), moroctocog alfa (72), octocog alfa (73), simoctocog alfa (104), turoctocog alfa (104)
  • Factor IX: -nonacog → nonacog alfa (77), nonacog beta pegol (104), trenonacog alfa (107)
  • Factor XIII: -tridecacog → catridecacog (99)
  • Recombinant von Willebrand factor: -vonicog → vonicog alfa (102)

5. Current Challenges

• The field is becoming increasingly complex with the development of new biotech products.
• The WHO is continuously reviewing and updating naming policies to ensure clarity and consistency.
• The document serves as a living resource, with future updates expected to reflect new naming schemes and product categories.