Patent Landscape Report on Ritonavir - WIPO

of preparing a compound reaches beyond simply licensing for the initial disclosure and synthesisstrategies. One of the most important aspects that could easily be overlooked whentrying to prepare a compound is access to key synthetic intermediates. Key intermediatesare defined as a compound, which is produced in the course of a chemical synthesis, whichis not itself the final product, but is used in further reactions to produce the final product. Thekey intermediates are compounds that are converted to Ritonavir through common chemistrysynthetic routes. Often these intermediates that are critical precursor for preparing Ritonavirare under patent protection. The main key ingredient is the central portion of the moleculethat is described as 1,6-diphenylhexane. Key intermediates are also important because theycan often be used to prepare several Ritonavir analogs that are all described in the initialAbbott Laboratories patent application WO1994014436. This innovation track highlightsseveral key intermediates required to prepare Ritonavir. Using current synthetic strategiesRitonavir could not efficiently be prepared without licensing of these key intermediates.The first generation patent application WO1994014436, assigned to Abbott Laboratories, isthe first disclosure of Ritonavir. The ‘436 document claims a broad Markush structure describingRitonavir. This initial document only claims a retroviral protease inhibitor and doesnot describe possible synthetic strategies, methods or intermediates.The second generation document is WO1995011224 (Abbott) and cites the ‘436 document.This document claims a synthesis of the Markush backbone for Ritonavir in the ‘436 document.While this intermediate is not claimed to be directly converted to Ritonavir it is still animportant intermediate worth noting. Claiming synthesis of this backbone would also be importantfor protecting synthesis of Ritonavir analogs.The third generation includes two patents WO1995023793 (Daicel) and WO2001021603 (Archimica/Clariant)and a 2B document US6407252 (Clariant). WO1995023793 describesnovel synthetic methods to prepare the substituted 1,6-diaminohexane present as the backboneof Ritonavir. This document was published shortly after the key patent(WO1994014436) so this is not the only intermediate but it could be a very important documentin the future for new methods of preparing Ritonavir or similar analogs. The ‘793document and its granted EP0748801 both describe the same preparation of key intermediates.The second third-generation document is WO2001021603, and its granted patentUS6407252 (2B). These documents describe a process to prepare Ritonavir using only fiveintermediate stages. This synthetic route is extremely efficient. The important advantage ofthis synthesis is that it uses the same starting materials as the first generation ‘436 document,but performs the synthesis with fewer reactants and materials making this a particularlyattractive route because it is both environmentally and economically conservative. Theclaims are more restrictive than expected for a second generation synthesis, but due to thehighly efficient method of preparing this severely limits other patents from preparing Ritonavirin a similar manner. IT999MI01950, which is located below the ‘603 and ‘252 documentsis the priority document for this family from which the broader family members coveringsynthesis than the ‘252 document claim priority.Please note PCT application WO1995023793 (Daicel) is included in the associated database;although the database only contains documents that specifically describe or are relatedto Ritonavir. However, this document is note-worthy in the context of this report, and