Patent

IPAB sets aside patent office order refusing crystalline form patent of Vorapaxar


Ever filed a patent application and have a rejection issued without any explanations? With the recent IPAB order, hopefully we won’t be having more of that anymore.

In this case the patentee/appellant (Plough Schering now Merck) had filed a patent application claiming a particular crystalline form of a thrombin receptor antagonist, Vorapaxar. In 2009, the patent office passed an order rejecting the patent application under Section 15 citing lack of inventive step and lack of proof regarding therapeutic efficacy of the crystalline form. The IPAB opined that the patent office had not sufficiently articulated reasons for refusing the patent and set aside the order. The IPAB then directed the patent office to consider the matter afresh by affording sufficient reasonable opportunity to the applicant/appellant to substantiate/amend their claims. The IPAB order can be accessed here.

Image from here

Factual Matrix:

The patentee had filed a patent application 2491/CHENP/2006 claiming a particular crystalline polymorph of a bisulfate salt of Vorapaxar characterized by X-ray diffraction. Vorapaxar is a thrombin receptor antagonist used in the treatment of acute coronary syndrome chest pain and is touted to become a blockbuster drug as the FDA panel recently voted in favor of approval. I couldn’t access the complete specification but the corresponding PCT application discloses that the crystalline polymorphic form is more stable and has improved thermodynamic properties over the parent compound. The Assistant Controller passed an order on June 2009 refusing the patent application on the grounds of lack of inventive step [Section 2(i) (j) (a)] and lack of evidence of enhanced therapeutic efficacy of the crystalline form [Section 3(d)].

The counsel for the patentee/appellant argued that the claims and contents raised by the appellants weren’t properly considered by the Controller and that the order did not sufficiently articulate reasons for refusal of the patent. The counsel for the Controller however contended that enough reasons were included in the order.

The IPAB order

The IPAB criticized the patent office order stating that it was very cryptic and a non-speaking one. The IPAB opined that the claims raised by the appellant were not considered in their entirety by the patent office. It also reasoned that Section 15 of the patents act affords opportunity to the applicant to make amendment in the application or to refuse the application on failure to submit any amendments.

Section 15 reads hereunder:

“Where the Controller is satisfied that the application or any specification or any other document filed in pursuance thereof does not comply with the requirements of this Act or of any rules made thereunder, the Controller may refuse the application or may require the application, specification or the other documents, as the case may be, to be amended to his satisfaction before he proceeds with the application and refuse the application on failure to do so.”

The IPAB further added stating “The reading of the above said provisions makes it abundantly clear that the learned Controller ought not to have mechanically refused the application and on the other hand he could have exercised discretion to give opportunity to the applicant/appellant by making amendments in the application.

My thoughts: 

I partially agree with the IPAB’s order and think that the patent office decisions leave much to be desired in terms of articulation skills and analytical rigor (read our previous posts on this here and here).

Having said that I also feel that, when an applicant submits a patent application with a claim for a crystalline polymorph form, they should have substantiated the claims with proof of enhanced therapeutic efficacy in the specification in the initial stages itself. After all, the Supreme Court in the Novartis decision (see Prashant’s analysis of the Novartis decision over here) made it abundantly clear that efficacy in the context of Section 3(d) should be construed as therapeutic efficacy. “What is evident, therefore, is that not all advantageous or beneficial properties are relevant, but only such properties that directly relate to efficacy, which in case of medicine, as seen above, is its therapeutic efficacy.”  For more on Section3 (d) and interpretation of the term efficacy, please read Shamnad’s paper here.

A note of caution: Foreign patent applicants.

Section 3(d) is unique to the Indian patent act. Foreign applicants typically seek patent protection by filing PCT applications designating India. Since proof of efficacy for patent applications relating to crystalline form of pharmaceutical drugs is a uniquely Indian requirement, oftentimes the specification does not include data showing proof of enhanced therapeutic efficacy and arenot specifically tailored to suit Indian patent law requirements. As a result lot of patent applications (belonging to foreign MNC’s/ applicants) end up getting refused/invalidated. Proof of enhanced therapeutic efficacy for Section 3(d) is indeed an onerous requirement, but any slackness in compliance can adversely affect the validity of the resultant patent.

Madhulika Vishwanathan

Madhulika Vishwanathan

Madhulika is a registered Indian patent agent and has completed her Master’s in Pharmacology from the Institute of Chemical Technology (ICT), Mumbai. Her interests include issues involving pharmaceutical and biotechnology patent law, regulatory aspects like Hatch Waxman litigation and antitrust law.She is currently working at law firm based out of Memphis, TN.

16 comments.

  1. Avatarkamal

    “they should have substantiated the claims with proof of enhanced therapeutic efficacy in the specification in the initial stages itself”

    i am not sure if it will be wise for applicants to wait for results of therapeutic efficacy before filing the application … it may take few years through clinical trials and all to provide any concrete proof of therapeutic efficacy… and I am not convinced that Supreme Court said the proof of efficacy should be provided in the patent application itself…. nowhere in the judgement it said that later discovered proof (therapeutic efficacy of the drug discovered after filing of patent application) may not be used … let me know if i am wrong..

    Reply
  2. Madhulika VishwanathanMadhulika Vishwanathan Post author

    Hi Kamal,
    Thanks for your comment.Interesting question.
    Therapeutic efficacy can be demonstrated by showing comparative increase in vivo absorption .It doesnt necessarily have to involve clinical trials,it can be proven in animal models.
    Also I never said that the Supreme court decision stated that the required data should be provided in the initial filing itself. I just thought it would be easier for the applicant to present the data after PCT filing,before national phase entry during the 30 months window (via art 19 or art 34 amendments).

    Reply
  3. Madhulika VishwanathanMadhulika Vishwanathan Post author

    Also for more details on standard of proof for therapeutic efficacy,please read Shamnad’s article (hyperlinked in the penultimate para of my post).
    if reasonably correlated to the particular therapeutic or pharmacological utility, data generated using in vitro assays, or from testing in an animal model or a combination thereof almost invariably will be sufficient to establish therapeutic or pharmacological utility for a compound, composition or process.

    Reply
  4. AvatarAnonymous

    Madhulika, take it from some one who knows the actual working of the patent office and the Courts in this context-(Section 3(d). Therapeutic efficacy in the specification!?
    Aha and bioavailability… I respect you guys and Shamnad too but you guys just write on the surface and most times without touch with the actual reality.

    Give me a single case which was opposed but overcame Section 3(d) in the context of therapeutic efficacy. It is like saying don’t get wet but go for a swim. If you find one, you would be right. Don’t bother with the ones where section 3(d) was waived aside by the controller in prosecution. Practitioners should appreciate the vagueness the SC helped pervade in the Novartis case.

    And yes, please don’t block this!!

    Reply
  5. Madhulika VishwanathanMadhulika Vishwanathan Post author

    Hey Anon,
    In the Section 3(d) context the applications which are opposed are typically very expensive blockbuster drugs. So public interest and a lot of other factors come into play when the decision is made.

    In the prosecution stage this case (106/DELNP/2008 ) is a good example of how the applicant proved enhanced therapeutic efficacy by showing comparative increase in in vivo absorprtion.
    http://164.100.176.38/decision/106-DELNP-2008-2054/106%20delnp2008%20decision.pdf

    Also the case I have discussed above is for a decision u/s 15 not an opposition appeal.

    Reply
  6. AvatarAnonymous

    Hi Madhulika:
    Do you have the original June 2009 order by the Controller rejecting the patent application – 2491/CHENP/2006?? Can you share please?

    Reply
  7. AvatarAnonymous

    Madhulika,
    Public interest is not a ground of opposition or revocation. It may be factored in while deciding a compulsory licensing issue or for granting injunction but is not a ground for opposition or revocation as indicated by you in so called block buster drugs.

    I understand the present decision is a Section 15 refusal case and I know about scores of cases where so called efficacy has been established in prosecution cases. However, my question is isn’t it obvious why none of these data are interpreted in contested cases in favour of the patentee/applicant? That is because the concept of ‘efficacy’ itself remains vague, which I reiterate is made murkier by the SC judgement .

    Hope you appreciate my point.

    Reply
  8. Madhulika VishwanathanMadhulika Vishwanathan Post author

    Hi Anon at 10:27pm,
    For some reason, I couldn’t access the complete specification or the order of the this Indian patent appn.

    Reply
  9. Madhulika VishwanathanMadhulika Vishwanathan Post author

    Anon at 2:28 pm:
    Please take the pains to strain your eyesight and read my comment and post carefully. I never said that public interest is a ground for opposition/revocation!

    To answer your previous question; “Give me a single case which was opposed but overcame Section 3(d) in the context of therapeutic efficacy. It is like saying don’t get wet but go for a swim. If you find one, you would be right.

    IN patent application number 413/MUM/2003 was granted as patent number 242111
    claims a crystalline form of clopidogrel besylate.

    It survived not one but 4 oppositions and filed by different opponents and each case was decided by a different controller. The patentee prevailed and proved efficacy!

    Here are the claims:
    http://ipindiaservices.gov.in/patentsearch/GrantedSearch/pdfviewer.aspx?id=12
    Also here is the link to the order:
    http://ipindiaservices.gov.in/patentdecisionsearch/VIewdoc.aspx?application_number=ZGHa8tKpOHY34RPZSvwfEbKpvxIEj1+Ugkd4X+aVplIb5LJjI/m8eqHsAQZlGhlCs22rs+6dLoZwBM2EgkWsAg==

    Hope this helps and thanks for this interesting debate 🙂

    Reply
  10. AvatarYour frequent commentor

    Dear Madhulika:

    The Clopidogrel order is mired in controversy. If you investigate, a senior patent office staff faced criminal sanctions shortly around that period.

    Regards,

    Reply
  11. Madhulika VishwanathanMadhulika Vishwanathan Post author

    Dear FC,
    Thanks. After your comment I did a little bit of research. Agreed that this case is murky.But subsequent to that around two different controllers arrived at the same conclusion. Oh well 🙂
    best-Madhulika

    Reply
  12. AvatarYour frequent commentor

    Madhulika:
    The reasons that the subsequent controllers had to come to a similar decision are not in public domain. I know of small tidbits of information (but not enough) and honestly, would not rely on Clopidogrel order from Mum IPO versus the IPAB orders on salt rejection. In any case, our conversation does not help the earlier querist on Vorapraxar.
    Good day.

    Reply
  13. AvatarAnonymous

    Hi Madhulika @ 10:43 pm on Feb 6, 2014
    Thanks for providing the link for the original 2009 Controller’s decision, however I am afraid that the link does not lead to the decision page or provide the actual decision. I think the link is incorrect and I would be grateful if you can provide the correct link or the decision, if you may have one. Thanks

    Reply
  14. AvatarSometimes anon

    Madhulika,

    I am back not with a vengeance but with a small clarification. I reproduce your text below:

    In the Section 3(d) context the applications which are opposed are typically very expensive blockbuster drugs. So public interest and a lot of other factors come into play when the decision is made.

    Ok maybe you did not say public interest is a ground for opposition BUT You are unequivocally indicating that public interest has to be factored in while deciding oppositions? Please don’t run from that. I am saying cannot be even that PERIOD!

    As far as the Cadila case is concerned, you should be intelligent enough to go through the orders and the so called enhanced efficacy provided therein to see how different is it from all the cases which has been refused? Do you even have the professional taste to cite it as precedent? It’s all about the money!

    What I would like to reiterate is that for a typical polymorph case like this ( and others like salts, esters etc) or the Novartis case, there is nothing under the sun which you can put forward to surmount Section 3(d) in a contested proceeding. It is like holding up an umbrella to defend yourself against a nuclear strike! Pointless!!

    Hope you appreciate my thoughts.

    Reply
  15. Madhulika VishwanathanMadhulika Vishwanathan Post author

    Sometimes anon:
    In your exuberance to comment, you haven’t bothered to read carefully again! I did not say public interest has to be factored in.public interest is already a factor irrespective of whether you and I like it or not.

    As for the rest of your disgruntled rant -you are entitled to your opinion.
    Its a lot better if the data required for Section 3(d) is presented in the initial stages instead of waiting for an opposition to present the data. That’s precisely the point of my post.

    Also a lot of applicants disclose the salt form in the product patent in the priority document. Then they try to claim the same salt in a separate patent. This in addition to Section 3(d) makes the salt form patent vulnerable to attack.

    Reply
  16. AvatarSometimes anon

    Madhulika!

    I reproduce you quote

    Also a lot of applicants disclose the salt form in the product patent in the priority document. Then they try to claim the same salt in a separate patent. This in addition to Section 3(d) makes the salt form patent vulnerable to attack.

    That’s how the world is- round and not square. that’s the drug discovery process!!

    I cannot help it if you cannot appreciate the big picture with your myopic view. It is just not possible to include trial data in the specification!

    Anyways, keep on with your tip of the iceberg stories. I give in..

    Reply

Leave a Reply

Your email address will not be published.