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Speaker at Drug Delivery Events - Mikhail Samuilovich Goizman
Drugs Technology LLC, Russian Federation
Title : INN Darunavir. Patenting problem of active pharmaceutical substances


One of the best HIV-protease inhibitors is [(3R,3?S,6?R)-hexahydrofuro[2,3-b]furan-3-ol](1S,2R)-3-[[(4-aminophenyl) sulphonyl] (isobutyl) amino]-1-benzyl-2-hydroxypropyl]carbamate (I) (INN Darunavir). PREZISTA and KEMERUVIR drugs contain Darunavir active pharmaceutical ingredient (API): the first one – in the form of crystalline ethanolate, the second one in the amorphous form. As HIV-protease inhibitor, compound I, its chemical structure and production process were at first time described in the patent “Hydroxyethlaminosulphonamides useful as retroviral protease inhibitors”, which has been enjoying conventional priority since August 24, 1993. INN Darunavir was suggested to honor prof. Arun K. Ghosh, the author of the research work. The production process for Darunavir amorphous using its ethanolate was described 16 years later in the patent “Polymorphs of darunavir”, which has been enjoying conventional priority since January 29, 2009. With due regard to the patents, the date when clinical studies of compound I (i.e. DRV) under code name of ??? 114 began, and the decision by FDA USP dated June 23, 2006 authorizing the use of PREZISTA®tablets, containing specifically Darunavirethanolate as their API, it must be acknowledged that it has been de-facto used as API since 2001. The dosage of PREZISTA® tablets is indicated in equivalent of compound I (INN Darunavir). Despite publication of the work, Tibotec Pharmaceuticals Ltd. filed a patent application on May 16, 2002, No 02076929.5, with a title containing undefined information: “Pseudopolymorphic forms of a HIV protease inhibitor”.

The application described compound I as HIV protease inhibitor under its chemical name and without the indication of INN, which allowed, without focusing on the lack of novelty, to claim as subject of patenting a number of solvates (pseudopolymorphs) of compound I allegedly derived from its amorphous form. Among others, the ethanolate of compound I was claimed, while its clinical tests had been started back in 2001. Then, Tibotec Pharmaceuticals Ltd. filed the application No. PCT/EP2003/050176, according to which parallel patents were issued with conventional priority dated 16.05.02. The article shows that the above patents containing false information, chemical and terminological errors have no right to exist. It is obvious that the applicants neglected the requirements of ethics, because they attempted to illegally monopolize the production of vitally important API, i.e. DRV ethanolate.

Takeaway Notes:
The paper deals with specific difficulties associated with attempts to reuse patented API. It shows that re-patented work API with INN Darunavir performed in violation of ethical standards. In addition, the patent authors were allowed chemical and terminological mistakes, indicating the lack of qualifications of the authors. This report is a useful example, demonstrating a principled approach to assessing attempts at secondary patenting of APIs, for the purpose of monopolizing their production and use.


Mikhail Samuilovich Goizman was born in Moscow, in 1939. In 1961 he graduated from the Moscow Chemical Technology Institute “MHTI” (now Dmitry Mendeleev University of Chemical Technology) specializing in the technology of petrochemical synthesis, from 1965 to 1998 worked in the All-Russian Scientific Research Chemical-Pharmaceutical Institute. The author of a number of General Pharmacopeia monographs in the State Pharmacopoeia of the USSR and Russia. At present Deputy General Director of “Drugs Technology” LLC. In 1972 defended the dissertation “Thermocatalytic titration of bases in a medium of protogenic solvents”, Ph. D., Laureate of State Prize “Council of Ministers of the USSR”. Area of scientific interests: analytical chemistry, synthesis and quality control of APIs. Ethical problems of patenting in the field of pharmacy