India: IPO Rejects Patent Application For Xtandi (Prostrate Cancer Drug)


The India Patent Office in its order issued on 18th November 20161, has denied a patent for the prostate cancer drug sold under the brand name Xtandi (generic name Enzalutamide). Xtandi was developed at the University of California, Los Angeles (UCLA) (Applicant) for fighting prostate cancer which is commercially sold in India by ASTELLAS PHARMA. The drug is currently sold at Rs 3.35 lakh2 for a pack of 112 capsules normally to be taken by a patient in a month's time, accordingly, which amounts to Rs.11,000 approximately per day.

The provision of pre-grant opposition under Indian Patents Act enables any person to file notice of opposition on Form 7A at the Indian Patent Office (IPO) after the publication of an application for patent. Therefore, by way of pre-grant oppositions any person can assist the Controller of Patents in evaluating the application for patent. IPO has seen a surge of pre-grant opposition, especially in pharmaceutical applications and the said applications are scrutinized in detail because of the same. IPO is often regarded as being stringent on allowing grant of patent on drug compositions. The TRIPS agreement3 contains flexibilities that were enhanced and clarified during the 2001 Doha Declaration on TRIPS and Public Health. The said agreement states, for instance, that for pharmaceutical patents, there is a flexibility to interpret and implement TRIPS provisions in a manner supportive of the government's right to protect public health.

Coming back to the instant case of Xtandi, the pre-grant oppositions was filed by a bunch of companies, including, Fresenius Kabi Oncology (Opponent 1), BDR Pharma (Opponent 2) and Indian Pharmaceutical Alliance (Opponent 4) as well as individuals: Mr.Umesh Shah (Opponent 3) and Ms. Sheela Pawar (Opponent 5). The main grounds of opposition were lack of novelty, lack of inventive step, and that the claimed compound did not constitute an invention under Section 3(d) relating discovery of new form of known compound and with efficacy test and Section 3(e) relating to mere admixture resulting in aggregation of properties of compounds of the Patents Act, 1970.

The Application:

The present application relates to diarylhydantoin compounds including diarylthiohydantoins and methods for synthesizing them. The claimed compounds of the said application are used for the treatment of hormone refractory prostrate cancer. The application was initially filed as PCT national phase with 46 claims. In the reply to first examination repot (FER) issued by the Patent Office, the Applicant reduced the number of claims to 15 and further only 3 claims were retained pursuant to an official hearing with the Controller of Patents.

Grounds of Opposition and Prior Art relied on:

The following are the grounds and the documents relied on by the opponents:

S. No. Sections Documents Cited Comments
1 Section 25(1)(b)- Lack of Novelty US5411981 (US'981) US6087509(US'509) 2440/DEL/1996 US 5434176(US'176) US 5750553(US'553)
  • US'981 already disclosed Enzalutamide; US'509 disclosed a family of compounds phenyl, phenylimidazolidines represented by a Markush structure including the compound claimed in the present invention. US'509 also disclosed the use of compounds for anti-androgenic activity useful against tumors.
2 Section 25(1)(e)-Lack of Inventive step US5411981(US'981)
  • Obvious selection of cyano group, CF3(Trifluoromethyl), fluoro-N-Methylbenzamide (or aryl substituted with fluoro and methylcarbamoyl) groups from the generic disclosure of US'981, US'257 and US'505
  • Formation of imidazolidine ring already a known process in view of US'578
  • US'509 disclosed compounds which are similar to enzalutamide maintain the same hydantonin moiety attached to a phenyl ring further substituted by a cyano and a trifluoromethyl group.
3 Section 25(1)(f) Not an invention u/s 3(d) Not an invention u/s 3(e) US4511981(US'981)
  • US'981 disclosed compounds which are structurally similar to Enzalutamide. Therefore, enzalutamide is a derivative of the known compounds of US'981.
  • The compounds claimed in claims 3-12 of the present application is a mere admixture of the compounds Enzalutamide as claimed in claim 1 and there is no demonstrated synergy in the present application.
4 Section 25(1)(g)- Lack of clarity and Sufficiency
  • Best mode of performing the invention is not mentioned.
  • Markush structure mentioned in the specification of present application encompasses several diaryl hydantonin compounds
  • Superiority of compound RD162' is not demonstrated in the specification.
5 Section 25(1)(h)- Section 8 requirement not completed The details with respect to all the foreign applications in respect of the same/substantially same invention were not disclosed completely in accordance with the requirement of Section 8(1) and (2) of the Act.

Applicant's Arguments:

  • With regards to lack of novelty, the applicant submitted that the cited prior art documents do not disclose any diaryl compound or any other compound that is even closer to the structure of Enzalutamide.
  • With regards to lack of inventive step, the applicant submitted that citation US'981 does not talk about methylcarbamyl group and that US'981 suggests acetamido group which is different than the methylcarbamoyl group. The Applicant further submitted that the compounds disclosed or taught under the cited documents are structurally dissimilar and have dissimilar modes of action and therefore the said documents fail to guide the person skilled in the art to perform the present invention as envisaged in the present patent application.
  • With regard to Section 3(d), the Applicant submitted that Enzalutamide the claimed compound is a New Chemical Entity (NCE) and the same is not a salt, ester, ether, polymorph, derivative, etc. of a known substance. Therefore, Enzalutamide cannot be regarded as the known substance under Section 3(d).
  • With regard to Section 3(e), the Applicant submitted that the revised claims disclose a novel diaryl thiohydathoin compound, Enzalutamide, a new chemical entity and therefore the combinations of Enzalutamide would be new and inventive which cannot be considered as an aggregation of the known properties of the components.
  • In response to ground of lack of clarity and sufficiency as per Section 25(1)(g), the Applicant submitted that the present invention is sufficiently disclosed to the fullest extent with sufficient working examples, synthetic schemes and test procedures to determine the biological activity of the disclosed compounds.

RD162 is specifically disclosed as Example 56 in the complete specification. In response to ground of non-compliance with Section 8, the Applicant submitted that, the information related to the corresponding foreign patent applications has been submitted to the Learned Controller at regular intervals, therefore the Applicant pleaded to dismiss the aforesaid ground of opposition.

Section 25(1)(b)

The Controller observed that none of the documents cited by the Opponents specifically disclosed the structure of the compound as claimed in the present application either by the way of claim or as an example. The claimed compound can only be arrived by suitable substitutions of different R group and X,Y,A,B etc. The Controller further pointed that to arrive at the structure of Enzalutamide, a person has to pick some suitable substituents from the definition given in markush structure as given in prior art and hence picking and putting is not allowable in ascertaining the novelty of the claimed invention. Therefore, the Controller dismissed the ground, reasoning that the claimed compound is novel and not anticipated in view of the cited prior art documents.

Section 25(1)(e)

The Controller observed that US'981 clearly mentioned that even moderately sized groups are not favored at ortho and meta position of the aryl ring. That leads to the only option is halogens out of the disclosure given in US'981 at this position. The Controller further mentioned that the applicant has failed to show in their application that fluoro substitution has any effect on the activity and there is no difference in activity of RD153 and compound that doesn't have fluoro substitution at this position and Enzalutamide. Also, the fluoro-N-Methylbenzamide moiety is clearly in the prior art US'257. Further, the formation of imidazolidine ring was already known in the art in view of US'578. Hence, the Controller stated that the claimed invention lacked inventive step in vide of US'981 in combination with US'257 and US'578.

Section 25(1)(f)

As the claimed compound Enzalutamide lacks novelty and inventive step due to the aforementioned reasons, the applicant's claim that the compound is a new chemical entity was denied by the Controller. Further the applicant failed to demonstrate an improvement in efficacy thereby making the claim unpatentable under section 3(d) of the Act.

The Controller further stated that the applicant in the present invention failed to show any synergistic effect when the compound Enzalutamide is used as a composition. Hence, the Controller accepted the opponent's objection to the application under to Section 3(e) of the Act.

Section 25(1)(g)

The Controller refused the ground of opposition for lack of sufficiency as the specification fully and sufficiently describes the claimed invention. Enzalutamide (RD 162') is specifically disclosed as Example 56 in the complete specification and its process for preparation is also disclosed.

Section 25(1)(h)

The Controller stated that the requirement of Section 8(1) and 8(2) was complied on different dates by filing the information regarding corresponding applications in other jurisdictions. Therefore, in view of the aforestated, the Controller dismissed the ground stated under section 8.


The Controller in his decision, refused to grant patent over Xtandi, as the claimed invention lacked inventive step under Section 2(1)(ja) and is not patentable as the claims falls under Section 3(d) and 3(e) of the Act.





The content of this article is intended to provide a general guide to the subject matter. Specialist advice should be sought about your specific circumstances.

To print this article, all you need is to be registered on

Click to Login as an existing user or Register so you can print this article.

In association with
Up-coming Events Search
Font Size:
Mondaq on Twitter
Register for Access and our Free Biweekly Alert for
This service is completely free. Access 250,000 archived articles from 100+ countries and get a personalised email twice a week covering developments (and yes, our lawyers like to think you’ve read our Disclaimer).
Email Address
Company Name
Confirm Password
Mondaq Topics -- Select your Interests
 Law Performance
 Law Practice
 Media & IT
 Real Estate
 Wealth Mgt
Asia Pacific
European Union
Latin America
Middle East
United States
Worldwide Updates
Mondaq Ltd requires you to register and provide information that personally identifies you, including what sort of information you are interested in, for three primary purposes:
  • To allow you to personalize the Mondaq websites you are visiting.
  • To enable features such as password reminder, newsletter alerts, email a colleague, and linking from Mondaq (and its affiliate sites) to your website.
  • To produce demographic feedback for our information providers who provide information free for your use.
  • Mondaq (and its affiliate sites) do not sell or provide your details to third parties other than information providers. The reason we provide our information providers with this information is so that they can measure the response their articles are receiving and provide you with information about their products and services.
    If you do not want us to provide your name and email address you may opt out by clicking here
    If you do not wish to receive any future announcements of products and services offered by Mondaq you may opt out by clicking here

    Terms & Conditions and Privacy Statement (the Website) is owned and managed by Mondaq Ltd and as a user you are granted a non-exclusive, revocable license to access the Website under its terms and conditions of use. Your use of the Website constitutes your agreement to the following terms and conditions of use. Mondaq Ltd may terminate your use of the Website if you are in breach of these terms and conditions or if Mondaq Ltd decides to terminate your license of use for whatever reason.

    Use of

    You may use the Website but are required to register as a user if you wish to read the full text of the content and articles available (the Content). You may not modify, publish, transmit, transfer or sell, reproduce, create derivative works from, distribute, perform, link, display, or in any way exploit any of the Content, in whole or in part, except as expressly permitted in these terms & conditions or with the prior written consent of Mondaq Ltd. You may not use electronic or other means to extract details or information about’s content, users or contributors in order to offer them any services or products which compete directly or indirectly with Mondaq Ltd’s services and products.


    Mondaq Ltd and/or its respective suppliers make no representations about the suitability of the information contained in the documents and related graphics published on this server for any purpose. All such documents and related graphics are provided "as is" without warranty of any kind. Mondaq Ltd and/or its respective suppliers hereby disclaim all warranties and conditions with regard to this information, including all implied warranties and conditions of merchantability, fitness for a particular purpose, title and non-infringement. In no event shall Mondaq Ltd and/or its respective suppliers be liable for any special, indirect or consequential damages or any damages whatsoever resulting from loss of use, data or profits, whether in an action of contract, negligence or other tortious action, arising out of or in connection with the use or performance of information available from this server.

    The documents and related graphics published on this server could include technical inaccuracies or typographical errors. Changes are periodically added to the information herein. Mondaq Ltd and/or its respective suppliers may make improvements and/or changes in the product(s) and/or the program(s) described herein at any time.


    Mondaq Ltd requires you to register and provide information that personally identifies you, including what sort of information you are interested in, for three primary purposes:

    • To allow you to personalize the Mondaq websites you are visiting.
    • To enable features such as password reminder, newsletter alerts, email a colleague, and linking from Mondaq (and its affiliate sites) to your website.
    • To produce demographic feedback for our information providers who provide information free for your use.

    Mondaq (and its affiliate sites) do not sell or provide your details to third parties other than information providers. The reason we provide our information providers with this information is so that they can measure the response their articles are receiving and provide you with information about their products and services.

    Information Collection and Use

    We require site users to register with Mondaq (and its affiliate sites) to view the free information on the site. We also collect information from our users at several different points on the websites: this is so that we can customise the sites according to individual usage, provide 'session-aware' functionality, and ensure that content is acquired and developed appropriately. This gives us an overall picture of our user profiles, which in turn shows to our Editorial Contributors the type of person they are reaching by posting articles on Mondaq (and its affiliate sites) – meaning more free content for registered users.

    We are only able to provide the material on the Mondaq (and its affiliate sites) site free to site visitors because we can pass on information about the pages that users are viewing and the personal information users provide to us (e.g. email addresses) to reputable contributing firms such as law firms who author those pages. We do not sell or rent information to anyone else other than the authors of those pages, who may change from time to time. Should you wish us not to disclose your details to any of these parties, please tick the box above or tick the box marked "Opt out of Registration Information Disclosure" on the Your Profile page. We and our author organisations may only contact you via email or other means if you allow us to do so. Users can opt out of contact when they register on the site, or send an email to with “no disclosure” in the subject heading

    Mondaq News Alerts

    In order to receive Mondaq News Alerts, users have to complete a separate registration form. This is a personalised service where users choose regions and topics of interest and we send it only to those users who have requested it. Users can stop receiving these Alerts by going to the Mondaq News Alerts page and deselecting all interest areas. In the same way users can amend their personal preferences to add or remove subject areas.


    A cookie is a small text file written to a user’s hard drive that contains an identifying user number. The cookies do not contain any personal information about users. We use the cookie so users do not have to log in every time they use the service and the cookie will automatically expire if you do not visit the Mondaq website (or its affiliate sites) for 12 months. We also use the cookie to personalise a user's experience of the site (for example to show information specific to a user's region). As the Mondaq sites are fully personalised and cookies are essential to its core technology the site will function unpredictably with browsers that do not support cookies - or where cookies are disabled (in these circumstances we advise you to attempt to locate the information you require elsewhere on the web). However if you are concerned about the presence of a Mondaq cookie on your machine you can also choose to expire the cookie immediately (remove it) by selecting the 'Log Off' menu option as the last thing you do when you use the site.

    Some of our business partners may use cookies on our site (for example, advertisers). However, we have no access to or control over these cookies and we are not aware of any at present that do so.

    Log Files

    We use IP addresses to analyse trends, administer the site, track movement, and gather broad demographic information for aggregate use. IP addresses are not linked to personally identifiable information.


    This web site contains links to other sites. Please be aware that Mondaq (or its affiliate sites) are not responsible for the privacy practices of such other sites. We encourage our users to be aware when they leave our site and to read the privacy statements of these third party sites. This privacy statement applies solely to information collected by this Web site.

    Surveys & Contests

    From time-to-time our site requests information from users via surveys or contests. Participation in these surveys or contests is completely voluntary and the user therefore has a choice whether or not to disclose any information requested. Information requested may include contact information (such as name and delivery address), and demographic information (such as postcode, age level). Contact information will be used to notify the winners and award prizes. Survey information will be used for purposes of monitoring or improving the functionality of the site.


    If a user elects to use our referral service for informing a friend about our site, we ask them for the friend’s name and email address. Mondaq stores this information and may contact the friend to invite them to register with Mondaq, but they will not be contacted more than once. The friend may contact Mondaq to request the removal of this information from our database.


    From time to time Mondaq may send you emails promoting Mondaq services including new services. You may opt out of receiving such emails by clicking below.

    *** If you do not wish to receive any future announcements of services offered by Mondaq you may opt out by clicking here .


    This website takes every reasonable precaution to protect our users’ information. When users submit sensitive information via the website, your information is protected using firewalls and other security technology. If you have any questions about the security at our website, you can send an email to

    Correcting/Updating Personal Information

    If a user’s personally identifiable information changes (such as postcode), or if a user no longer desires our service, we will endeavour to provide a way to correct, update or remove that user’s personal data provided to us. This can usually be done at the “Your Profile” page or by sending an email to

    Notification of Changes

    If we decide to change our Terms & Conditions or Privacy Policy, we will post those changes on our site so our users are always aware of what information we collect, how we use it, and under what circumstances, if any, we disclose it. If at any point we decide to use personally identifiable information in a manner different from that stated at the time it was collected, we will notify users by way of an email. Users will have a choice as to whether or not we use their information in this different manner. We will use information in accordance with the privacy policy under which the information was collected.

    How to contact Mondaq

    You can contact us with comments or queries at

    If for some reason you believe Mondaq Ltd. has not adhered to these principles, please notify us by e-mail at and we will use commercially reasonable efforts to determine and correct the problem promptly.

    By clicking Register you state you have read and agree to our Terms and Conditions