India: Novartis Denied Patent for Gleevec

Last Updated: 31 May 2006
Article by Manisha Singh Nair


Patents are available only for inventions that are novel, non-obvious as well as useful. Therefore, where novelty is a bedrock concept of all patent systems, nonobviousness is the ultimate condition of patentability but first of all an invention i.e. a product of investigation and experiment must qualify as an invention. Section 3 of the Patents Act 1970 as amended by Patents (Amendment) Act 2005, in a very succinct way provides for what are not inventions. Clause (d) disqualifies a new form of a known substance which does not result in the enhancement of the known efficacy, as an invention. The Explanation further elaborates that salts, esters, ethers, polymorphs, metabolites, pure form, particle size, isomers, mixtures of isomers, complexes, combinations and other derivatives of the known substances are to be considered the same unless they differ significantly in properties with regard to efficacy.

In the light of this amendment made to usher India into an era of product patent regime, a new era in the Indian Pharmaceutical industry, based on innovation and new drug development, has been heralded. The instant provision of the Patents Act together with the opposition provision serves as a legal tool for both generic and pioneer pharmaceutical companies to challenge the validity of a claimed invention. The recent denial of the patent application for an anti cancer drug beta crystals of Imatinib mesylate filed by the Swiss pharma major Novartis AG and opposed by a cache of Indian pharma generic producers including Cipla and Ranbaxy, is the first major decision on patent application after India complied with the TRIPS regime in 2005 and is widely seen as a scenario of the Indian pharmaceutical industry in the product patent regime wherein opposition is an important tool to thwart off frivolous claims and also to obtain commercial benefits.


An application for patent was filed by M/s. Novartis AG on July 17, 1998 for an invention titled "Crystal Modification of A N – Phenyl – 2 Pyrimidineamine derivative, processes for its manufacture and its use" claiming Switzerland priority date of July18, 1997. The patent application in effect claimed beta crystal of methanesulphonic acid salt of 4-(4-methylpiperazin-1-ylmethyl)-N-[4-methyl-3-[4-pyridine-3-yl)pyrimidine-2-ylamino)phenyl]-benzamide commercially called as imatinib mesylate.

Cipla Ltd along with other generic producers filed their representation by way of opposition under section 25(1) of the Patents Act, 1970 as amended by Patents (Amendment) Act, 2005 and rule 55 of the Patents Rules, 2003 as amended by Patents (Amendment) Rules, 2005.


The arguments of the Applicant and the Opponents were on the following issues.

[1] Not an Invention

Anticipation by Prior publication


[2] Section 3(d) of the Patents Act

[3] Priority

As regards the First Issue the opponent contention was that imatinib mesylate is known from prior publications viz. Nature Medicine (May 5, 1996), Cancer Research (Vol.56, Issue I, 1996) and Blood (Nov.1 1997) besides already known from the US Patent no. 5521184 hence the subject matter of the application is anticipated the opponents tried to prove that there is no ingenuity or human intervention or novelty and inventive step in the preparation of beta crystal salt of imatinib mesylate as that is only a new form of a known substance and not an invention under the amended Patents Act.

The opponents further argued that the beta crystalline form is the most stable form of imatinib mesylate salt, which is also evident from the affidavit submitted by the applicant, which states that the beta form of the salt is thermodynamically more stable. The affidavit was based on the studies done by two reputed government institutions namely Indian Institute of Chemical Technology, Hyderabad and Indian Institute of Technology, Delhi. From their repeated studies and experiments the salt was found to steadily exist in the beta crystalline form. Also that, it is obvious for a person skilled in the art to prepare corresponding pharmaceutically acceptable salts once the freebase is known by the disclosure of the US Patent.

The applicants argued that the disclosure made in the US Patent is of the free base, ‘imatinib’ and not its salt, imatinib mesylate, therefore the present invention involves two-fold improvement over the prior art - [1] The imatinib free base is chemically changed into a salt form and [2] A particular crystal form, beta crystal form, of the salt is made through human intervention. Further that the US Patent does not give any example for the preparation of imatinib mesylate nor are there any claims made for it, however the US Patent may embrace imatinib mesylate.

It was held that the US Patent discloses methanesulphonic acid as one of the salt forming groups and the patent specification clearly states that the required acid addition salts are obtained in a customary manner. The claims 6 to 23 of the US Patent claim a pharmaceutically acceptable salt of the base compound and the patent term extension certificate, specifically mentions imatinib mesylate as the product. Thus imatinib mesylate is already known from prior publications. Also that imatinib mesylate normally exist in the beta crystals form which is thermodynamically most stable product.

Thus the opponents succeeded in proving that the invention of Novartis is obvious and anticipated by prior publication hence not an invention.

Under the Second Issue the opponents reiterated the submissions made under the first issue and further argued that the application claims only a Polymorphic form of imatinib mesylate and as regards efficacy the Patent application itself states that wherever beta crystals are used the imatinib freebase or other salts can be used equally in the treatment of diseases or in the preparation of pharmacological agents. To further corroborate the arguments, studies were conducted by technical experts to compare the relative bioavailability of the freebase with that of the beta crystal form of imatinib mesylate. A difference of 30% was found which, it was said, could be due to difference in their solubility in water. Therefore, it was argued that, the present Patent Specification does not bring out any improvement in the efficacy of the beta crystals over the known substance.

The applicant countering the argument said that section 3 (d) couldn’t be used against the subject application as the aspect of this section, that a discovery graduating into a patentable invention solely on the basis of efficiency defies logic and therefore unable to stand legal scrutiny. Further submitted that this aspect of section 3 (d) is against the tenets of the Patents Act as well as the established principals of jurisprudence and that the beta crystal form of imatinib mesylate is an invention, a new substance and not a mere discovery.

It was concluded on the basis of the above argument by the learned judge that as rightly argued by the opponents the subject matter of this application is not patentable under section 3 (d) of the Patents Act, 1970 as amended by the Patents (Amendment) Act, 2005.

The opponent’s contention under the Third Issue was that the patent application was filed on July 17, 1998 as a convention application claiming convention priority from an earlier Swiss application whereas Switzerland was not a convention country on that date, therefore the application deserves to be rejected on the ground of legal and technical disqualification.

The applicant responded by saying that the priority claim is discretion of the applicant and only a facility to avoid anticipation by prior publication of the invention between the priority date and filing date in India.

It was held that the patent application wrongly claims priority, hence legally and technically disqualified

In view of the above findings and all the circumstances of the case the learned judge in the instant case, Asst. Controller of Patents & Designs Mr.V.Rengaswamy, refused to proceed with the application for Patent


It was widely speculated that the product patent regime would destroy almost 15% of the existing Indian pharma market as the generic producer will have to withdraw the product when the patents controller accords patent to any of the mailbox applications. However domestic pharma companies were confident that many of these applications would not be patentable, as mailbox facility was designed to facilitate patent filings for drugs discovered between 1995 and 2005 only and that the number of new chemical entities discovered during that period is around 135 only, therefore a huge majority of the pending mail box applications would either be frivolous or those for salts, isomers, metabolites, polymers, solvents or such modification of an already patented entity.

© Lex Orbis 2006

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