After a roller coaster ride from the patent office to the High Court and back to the Patent Office, the application for Patent for Sovaldi (Sofosbuvir) has now finally seen the sun. The Indian Patent Office has upheld the patent application of Gilead for Sofosbuvir. The Dy. Controller of Patents and Designs, Mr. Rajesh Dixit, in a 58 page order has found the application for patent to be novel, inventive and outside the prohibitory ambit of Section 3(d).
The Indian Patent office had earlier in January 2015 rejected the same application under Section 3(d) of the Indian Patents Act. Instead of appointing hearings on the pre-grant oppositions, the erstwhile Controller appointed a hearing under Section 15. The Controller did not consider the data on reduced toxicity and rejected Gilead’s patent application under Section 3(d). Gilead had filed a Writ Petition before the Delhi High Court against the Order of the Controller stating that the same was biased and was largely influenced by the opposition filed to the extent that typographical errors in the oppositions filed were incorporated as it is in the order. Gilead further claimed that the order was biased as no opportunity of being heard was given to the Petitioner with regard to the grounds raised in the oppositions. The order was set aside and the matter was remanded back for a fresh hearing by the Delhi high Court.
Dr. Rajesh Dixit heard the matter at length between 23rd to 29th February 2016 and vide an order dated 9th May 2016 reversed the previous order refusing the grant. The following are noteworthy findings in the decision of the Controller:-
1) The application discloses (2’R)-21-deoxy-2’-fluoro (down)-2’-C-methyl (up) nucleosides, as well as their corresponding monophosphate, diphosphate and triphosphate forms. The claimed compounds require methyl group at the 2’(up) position and a fluorine at the 2’(down) position of the sugar ring, a cytosine or uracil base attached to the sugar ring at 1 position nitrogen in the base ring.
2) The Controller noted that this substitution is unique and there is neither exemplification nor enabling disclosure in any of the cited prior art documents, including the closest prior art WO425, of the compounds claimed in the present application. The claimed compounds which have not be exemplified in any prior art cannot be deemed to be a part of the prior art.
3) Cherry picking of substituents from prior art is not allowed and the substituent in the Markush formulae provided in the prior arts have to be understood in the context of the invention contained in the examples, process for preparation and overall teaching of the document. Arbitrary selection of the substituents to arrive at hypothetical compounds is not possible without hindsight.
(b) Inventive Step
4) The Controller held that the compounds enabled by the prior art do not have 2’-fluoro (down)-2’-C-methyl (up) substitution pattern, which has been claimed in the present application. From the teachings of prior art, in particular WO425, it is difficult for POSA to arrive at a substitution pattern as presently claimed. There is no motivation or guidance towards the unique substitution pattern of the compounds of the present application in WO425 or any other prior art document.
5) A person skilled in the art would not be motivated to select a compound for further research from prior art unless the same is enabled or listed as a promising compound. Selecting a hypothetical compound requires some motive. The opponent has not provided any motivation for selecting said imaginary compound for the inventive step analysis.
6) POSA was further well aware of the unpredictability of fluorination on drug metabolism and unpredictability of fluorination using reagents such as DAST and substantial experimentation would have been required at the priority date to arrive at the claimed compounds which therefore, cannot be obvious.
(c) Section 3(d)
7) The Controller held that the compounds claimed are outside the prohibitory ambit of Section 3(d).
8) Nucleosides and other analogues are known in the art and in further research in the field there is bound to be similarity in core structure of any new nucleoside analogue invented. This cannot be understood to mean the structural similarity in field of chemistry. Further if such compounds are considered to be structurally similar and a derivative then the issue will be that what would be the known substance against which the enhanced therapeutic efficacy has to be shown.
9) The compounds argued to be known substances for the present case are hypothetical compounds which are not exemplified. The processes described in the prior art will not lead to the claimed compounds. In other words, the claimed compounds can be visualized in the prior art only by way of hindsight. An applicant cannot be required to make a compound which was not in existence as on the priority date for showing comparative activities.
10) Further, the claimed compounds are not polymorphs, isomers, salts etc. of a known compound and therefore are not derivatives of any known compounds. The process for the preparation of the claimed compounds shows that the claimed compounds are not derived from compounds having 2’methyl (up) or 2’-hydroxyl (down) substitutions.
11) In addition, the applicant has provided comparative activity and toxicity data vis-à-vis compounds having 2’methyl (up) substitution and 2’-hydroxyl (down) substitution i.e. 2’-C-methylcytidine and 2’-C-methyladenosine. The drug cover by the claims of the present application has shown excellent efficacy as against all the known medicines for HCV.
12) Though the Opponents argued that the claimed compounds are not sufficiently described in the complete specification this claim has not been supported by any reason. The specification provides examples, schemes of synthesis, experimental data, figures, comparative activity and toxicity data. Therefore, a person skilled in art will able to perform the invention in view of the description of the patent application.