Rethinking the INN system for therapeutic antibodies

Abstract

In the context of a possible revision of the International Nonproprietary Names (INN) system of recombinant monoclonal antibodies, which is saturated, we propose several avenues of reflection driven by the primary goal of the INN, information of health-care professionals. Clinical considerations argue for an abandon of the substems A (target category) and B (origin category), which lengthen the INN without real added-value. On the contrary, new substems or suffixes are required to alert on the absence/presence of an Fc portion and/or multispecificity, which are essential from a pharmacological point of view. Moreover, we think it necessary to explicitly mention Fc variations since they could influence the pharmacology of these biopharmaceuticals, and hence their efficacy and side-effects. Besides indicating the subclass/isotype in the documents easily accessible to health care professionals, we propose to systematically describe both the natural variations (allotypes) by using the Gm (G marker) system, and the artificial variations by using a Ge (G engineering) system that is discussed here and could apply to all IgG constant domains (tentatively called the Fy portion).

Nomenclature of humanized mAbs: Early concepts, current challenges and future perspectives

“…Therefore the authorities decided to define a humanized antibody not by the protein engineering technique, which developed into a broad spectrum of approaches (Table 3) but rather calculated the percentage of identity to the nearest related germline, which must be of human origin. This approach was defined in 2014 but the scientific community voted rightly against this projection [30, 44, 48] since also originally human antibodies might not assign the name human (i.e. ‘umab’) or humanized (i.e.…”

Use of monoclonal antibodies in cancer immunotherapy: types and mechanisms of action

“…The names of mAb of chimeric origin are characterized by the suffix -ximab. Unlike fully murine antibodies, this antibody format usually has a prolonged half-life in humans and shows reduced immunogenicity; however, the tendency of chimeric mAbs to induce HAMA remains considerable 46 . The first FDA-approved antibody of this type was used in patients with non-Hodgkin's lymphoma and is recommended as a single agent after relapse; however, options to increase its efficacy and decrease the failure rate are still being explored 47 .…”

Past, Present, and Future of Rituximab—The World’s First Oncology Monoclonal Antibody Therapy

“…In 2013, obinutuzumab (trade name Gazvya) became the first glycoengineered antibody approved in the US as the next generation of anti-CD20 mAb for cancer treatment. The glycoengineering is accomplished by overexpressing two glycosylation enzymes, MGAT III and Golgi mannosidase II which resulted in antibodies that are mostly non-core-fucosylated and possess unique properties distinct form regular IgG1 ( 100 ). mAbs of this particular subisotype are also referred to as IgG(1E5) ( 100 ).…”

“…The glycoengineering is accomplished by overexpressing two glycosylation enzymes, MGAT III and Golgi mannosidase II which resulted in antibodies that are mostly non-core-fucosylated and possess unique properties distinct form regular IgG1 ( 100 ). mAbs of this particular subisotype are also referred to as IgG(1E5) ( 100 ). These modifications create better binding of effector immune cells and a more efficacious response compared with rituximab, although the clinical benefits have been variable.…”