2022-10-11-世界卫生组织-INN_Bio_Review_2022_136页_1mb

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

Core Content

The World Health Organization (WHO) has established the International Nonproprietary Names (INN) system to provide unique, globally recognized names for medicinal substances, including biological and biotechnological ones. This system ensures that names are non-proprietary and not tied to commercial rights, allowing free use by all stakeholders. The document reviews the current status of INN naming conventions for these substances, highlighting the evolution of the system over time to accommodate new developments in biotechnology.

Main Viewpoints

• INN Purpose: To ensure global recognition and standardization of biological and biotechnological substances.
• Stem Usage: Stems are used to classify substances with similar structures or functions, aiding in identification by health professionals.
• Nomenclature Evolution: The naming system has evolved significantly, especially for monoclonal antibodies, fusion proteins, and pegylated substances.
• Policy Decisions: The WHO has made several policy decisions to manage naming complexity, particularly for substances with multiple pharmacological functions or components.

Key Information

1. Current Status of Stems or Systems

Groups with Their Stems

Groups with INN Nomenclature Schemes

• Fusion proteins with more than one pharmacological active component
• Monoclonal antibodies
• Substances for cell therapy
• Substances for cell-based gene therapy
• Substances for gene therapy
• Substances for virus-based therapy
• Engineered or synthetic scaffold proteins with non-immunoglobulin variable domain derived binding domains

Groups without Stems / Pre-stems

• Antithrombins
• Growth hormone (GH) antagonists
• Insulins
• Interferons
• Pituitary / placental glycoprotein hormones
• Thrombomodulins
• Toxins
• Various

2. General Policies

2.1 Substances Identified by Their Proper Name

• Differences in amino acid sequence are indicated by a second word (e.g., insulin argine).
• Glycosylation is indicated by a Greek letter (e.g., insulin efsitora alfa).
• Specific linker components are also indicated by a second word (e.g., hemoglobin raffiner).
• Pegylation is indicated by a prefix (e.g., peginterferon alfa-2b).

2.2 Glycosylated Substances

• Glycosylation is indicated by a Greek letter (e.g., epoetin alfa).
• For monoclonal antibodies and receptor molecules, the Greek letter is used even if not explicitly included in the name.
• Exceptions exist for interferons, where small letters indicate different glycosylation patterns.

2.3 Fusion Proteins

• Fusion proteins with one pharmacologically active component use existing stems (e.g., -mab, -cept) and prefixes (e.g., -alb, -ef).
• Fusion proteins with more than one active component use the stem -fusp and infix letters for action and targeting (e.g., -ra-, -ba-).
• Infix letters are defined in Table 1, which includes meanings for both action and targeting components.
• If the targeting component is not an antibody, receptor, or antigen, the letter -o- is used.
• Bi- or multi-specific antibodies use the new antibody nomenclature scheme.

2.4 Pegylated Substances

• Two naming approaches are used: single-word with prefix "peg-" or two-word with "pegol".
• If the peg-linker is modified, a fantasy prefix is added to the name.
• For peptides, "peg-" can be used as a prefix or infix.

2.5 Gene Therapy Substances

• A two-word nomenclature scheme is used, with the first word identifying the gene component and the second word the vector.
• The vector component is identified by specific infixes (e.g., -adeno- for adenovirus, -lenti- for lentivirus).
• The current list of gene infixes is available in Annex 7.

2.6 Cell Therapy Substances

• Non-genetically modified cell therapy substances are given a one-word name ending in "-cel".
• Manipulation or modification details are included in the description, not the name.
• Infixes are used to identify the primary cell type (e.g., -astro- for adipose stromal cells, -leu- for lymphocytes).

2.7 Cell-Based Gene Therapy Substances

• A two-word name is used, with the first word for the gene component and the second for the cell component.
• The gene component is named as in gene therapy (see Table 2).
• The cell component is named using cell-specific infixes (e.g., -tem- for stem cells, -nepro- for neural progenitor cells).

Current Challenges

The field of biological and biotechnological substances is rapidly evolving, presenting ongoing challenges in naming and classification. The increasing complexity of these substances requires continuous review and updates to the INN system to ensure clarity and consistency.

Conclusion

The INN system continues to adapt to new scientific and technological developments in biotechnology. The document serves as a living review of the naming policies and practices, with regular updates expected to reflect new substances and naming schemes. It is intended to be a comprehensive reference for all stakeholders involved in the naming and classification of biological and biotechnological substances.