Category Archives: Section 3(D)

Germany’s Boehringer Repudiated Patent on HIV Drug- Nevirapine

The Indian Patent Office has repudiated Germany’s Boehringer Ingelheim patent on its key HIV drug- Nevirapine, Patent Application Number: 4724/DELNP/2009 entitled “Extended release formulation of Nevirapine”, for a version sold as Viramune XR (extended release), once again forestalling attempts by Big Pharma for “exclusivity” extension on their patented drugs to reportedly block entry of reasonably priced generics.

Boehringer Ingelheim, one of the few family-owned pharma company globally, is working on biosimilars, immuno-oncology and, new treatment options for psychiatric disorders like forms of depression or schizophrenia etc. Globally, it has a strong pipeline in oncology, respiratory, stroke and diabetes prescription medicines – all of which are of importance to the demographics in India, and some of which have already been launched in India. At present, the company has several patented drugs in the domestic market – Xovoltib (afatinib), two biologics Metalyse and Actilyse, Pradaxa anticoagulant, and two diabetes medicines named Trajenta and Trajenta duo.

Some Facts

Boehringer Ingelheim had filed a patent application (application number: 4724/DELNP/2009) in India on extended release of the HIV drug on 20th July 2009, against which, Cipla had filed a pre-grant opposition in 2011, and later on launched its generic version.

Reportedly, the applicant (Boehringer) did not respond to the pre-grant opposition and also did not appear at the hearing fixed for the same on September 15, 2015. N R Meena, deputy controller of Patents & Designs, said in the order, since the applicant did not appear in the hearing fixed under section 25(1) before the controller, and no arguments were offered to rebut the objections raised in the FER (first examination report), and by the opponent, the application for grant of patent is refused.

Objections raised in the First Examination Report (FER)

Some of the below mentioned objections were raised in the first examination report (FER):

  1. Claims1-7, 8-10, 11-14, 15-20 and 21-24 are rejected u/s 3(e) of the Patents (Amended)Act, 2005 as the said claims define a mere admixture resulting only in aggregation of the properties of components thereof.
  2. It is not clear if thecombined agents act together to provide a technical effect that is greater thanjust the sum of the two or more agents alone, or whether the combination is in fact a mere juxtaposition with no interaction of the agents.
  3. Claim 1 and dependent claims thereof do not constitute an invention under section
    2[1(j)] of Patents Act 1970 (as amended in 2005) as the claims lack inventive step in view of following patent documents:
  • US2002/0006439
  • WO00/035419
  • WO2007/047371
  • US2002/0068085

Grounds of Opposition

Some of the grounds of opposition that were raised and relied upon by the opponent in the pre-grant opposition include:

  1. Section 25(1)(e): Obviousness and Lack of Inventive Step

Opponent had presented numerous prior arts to demonstrate obviousness and lack of inventive steps for the claims of the impugned application.

  1. Section 25(1)(f): Not Patentable/ Not an Invention –
  • Claim lack inventive step under Section 2(1)(ja)

The claims of the impugned application falls under section 2(1)(ja) i.e. being devoid of inventive step. The definition of inventive step states that the invention should be a technical advancement over the prior art or it should show economical significance or both and should not be obvious to a person skilled in the art. It was also stated that the alleged invention is neither a technical advancement nor does it give any economic significance.

  • Claims not a invention as per section 2(1)(ta)

The challenged invention falls under Section 2(1)(ta), being devoid of inventive step as according to the definition of ‘pharmaceutical substance’.

  • Claims not patentable as per Section 3(d)

The alleged pharmaceutical product (dosage form) as claimed in the impugned patent application does not provide any additional advantage or therapeutic efficacy over the form(s) known in the prior art i.e. 400 mg immediate release form or 200 mg immediate release form.

  • Claims not patentable as per Section 3(e)

The claimed invention i.e. claims 1 and 2, falls under the Section 3 (e) which clearly states that a substance obtained by a mere admixture results only in a aggregation of properties of components thereof is not patentable. The alleged invention in the impugned patent application is a mere admixture of nevirapine and conventional excipients for extended release for once-daily administration without any demonstration of improvement over the prior art.

Previously, an objection under section 3(e) to the dosage form (pharmaceutical product) in claims 15 and 21 of the original claims was also raised in the First Examination Report.

  1. Section 25(1)(g): the complete specification does not sufficiently and clearly describe the invention or the method by which it is to be performed

Conclusion

After hearing all the parties and considering all facts, the Controller denied patent on HIV drug under Section 3(d) of Indian Patent act.

Please refer to the link (http://goo.gl/uw21Kh) for further information.

About the Author: Sugandhika Mehta, Patent Associate at Khurana & Khurana, Advocates and IP Attorneys and can be reached at:sugandhika@khuranaandkhurana.com.

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Revocation of Valganciclovir patent by Controller of Patents, Chennai

Recently in a matter remanded from IPAB to Controller of Patents, Chennai, a decision of revoking Roche’s patent IN207232 for Valganciclovir was delivered after hearing both the parties. The subject patent was granted on January, 2009 followed which post grant oppositions were separately filed by CIPLA, Matrix, Ranbaxy and Bakul Pharma along with two NGOs Delhi Network of Positive People and lndian Network for People living with HIV/AIDS & The Tamil Nadu Networking People with HIV/AIDS (hereinafter INP+ and TNNP+), wherein INP+ and TNNP+ were allowed by the Apex court to raise all contentions in the form of an intervention cum affidavit before the Assistant Controller and the parties agreed to be heard along with CIPLA, Matrix, Ranbaxy and Bakul Pharma. In the opposition proceedings, the patent was revoked limiting it to single process claim by the Controller of Patents on 30.04.2010 and being aggrieved by this decision, Roche filed an appeal at IPAB challenging the decision. IPAB on 30.01.2014 set aside the Patent Controller’s decision to revoke the patent on technical grounds and remanded it to the Controller for re-consideration.

Issues before the controller:

  • Determining whether the expert evidence was prior art publication or disclosure

Answering the issue, controller observes that the expert evidence is not a prior art document to be relied upon for deciding a case, but it may be considered for understanding the prior art documents, if the evidence covers such prior art documents. The opinion of the expert evidence, if it is based on further laboratory or animal study of a given subject matter, it cannot be considered for concluding such invention because it is later acquired knowledge, but it can be used for understanding the present invention. Therefore, expert evidences cannot be considered as prior publications/disclosures, but it can be taken as opinion on the prior arts.

  • Deciding upon the obviousness of the present invention

The next issue which the controller addressed was whether the present invention was obvious with respect to prior art references. The controller observes that the present invention is obvious against two prior arts US 4957924 and EP 0375329A2.

Claim 1 of the present invention recites,

  1. The compound 2-{2-amino-1, 6-dihydro-6-oxo-purin-9-yl} methoxy-3-hydroxy-1-propanyl-L-valinate or a pharmaceutically acceptable salt thereof, in the form of its (R) or (S)- diastereomers, on in the form of mixtures of the two diastereomers.

Regarding this , the controller states that the monovaline ester of ganciclovir is disclosed in the form of Markush formula in EP ‘329, which covers both monovaline and di-valine ester of ganciclovir where support for the both mono and di-valine ester of gancicloviris is provided in the specification. Thus the disclosure of EP ‘329 is clear and unmistakable direction to the mono valine ester of ganciclovir. Hence, a skilled person working in the synthetic chemistry field can easily arrive at the present invention without further experimentation. Therefore mono valine ester of present invention is anticipated by EP’329. Controller further emphasizes that claim 1 of EP ‘329 clearly and unambiguously discloses as at least one of the substituents is valine residue which indicate the presence of mono valine ester. Therefore, EP’329 undoubtedly disclosed mono valine ester of ganciclovir.

With respect to process claim, controller observes that the synthetic method for preparing mono valine ester of ganciclovir as claimed in independent claim 12 of present invention may not be explicitly disclosed in EP ‘329, but said method is just a general method for coupling acid group in the amino acid with hydroxyl group, which can be adopted for any type of alcohols. Therefore, using EP’329, a person working in the synthetic chemistry can easily prepare ester of ganciclovir with lysine without undue burden.

Further the controller observes that the object of the present invention is to provide a prodrug of ganciclovir with improved oral bioavailability. Controller notes that the solution for poor absorption in the gastrointestinal tract for acyclovir is disclosed in US ‘924 patent. Therefore a person skilled in the art can perceive to prepare mono valine ester of ganciclovir from the teachings of both EP’329 and US’924 references. Thus all the claims including process claim are obvious to a skilled person in the art.

  • Deciding upon the efficacy of substance under the subject patent under section 3 (d)

Deciding upon the efficacy of substance under the subject patent, the Controller observes that the new form L-monovaline ester of ganciclovir molecule has shown improvement in oral bioavailability than bis-valine ester of ganciclovir and ganciclovir, whereas there is no support in the specification pertaining to efficacy. Controller observes that the ester modification of the present invention was made to protect the substance from destruction in the gastrointestinal tract and make the molecule more bioavailable. Thus the controller has ruled that while bioavailability is one of the factors affecting efficacy, it cannot be directly equated to efficacy. Citing Hon’ble Supreme Court of India’s decision on Novartis case, the Controller rules that: “lmprovement in bioavailability of the new form cannot be considered directly related to efficacy. Even any unforeseen property observed in new form, unless such property directly relate to efficacy, it will be considered as inherent property of such substance. Since there is no direct relation shown for the improved bioavailability of new form of ganciclovir in the description with regard to significant difference in the efficacy, and therefore such a new form shall be considered as a same substance. Thus new form of the present case Monovaline ester of ganciclovir is considered as a same substance i.e. ganciclovir because,the difference in enhanced efficacy is not shown in the complete specification.” According to the controller, since there is no direct relation shown for the improved bioavailability of new form of ganciclovir in the description with regard to significant difference in the efficacy, therefore such a new form shall be considered as a same substance. Further regarding process used for preparing present invention, the controller held that the process used to prepare new form is a conventional process as it is already known process as disclosed in EP ‘329. Thus, the Controller rules that the present patent was a ‘mere use of a known process’ which was not patentable under S. 3(d), Patents Act.

  • Locus standi of the two NGOs as “person interested” under section 2(1)(t)

Deciding the locus standi of the two NGOs, as person interested under section 2 (1)(t) of patent act, Controller notes that NGOs would fall under the ambit of persons interested as the criteria of locus standi in post grant opposition is to be viewed in broader perspective to grant quality patent. According to the Controller, the two NGOs are the end users or directly affecting parties, if the patent is granted. Thus it is held by the controller that viewing in to the broader prospective, the two NGOs falls under the purview of under section 2 (1)(t) of the patent act and hence the parties have locus standi to oppose the patent.

Thus hearing all the parties and considering all facts and relevant arguments, the Controller revoked the patent granted for the drug Valganciclovir under section 25(4) of Indian Patent act.

About the Author: Mr. Sitanshu Singh, Patent Associate at Khurana & Khurana, Advocates and IP Attorneys and can be reached at: sitanshu@khuranaandkhurana.com.

Section 3(D) of Indian Patent Act Strikes Again

India revoked yet another drug patent granted to a German MNC, Boehringer Ingelheim, for its respiratory drug, Spiriva (crystalline tiotropium bromide monohydrate) at a time when the US is putting pressure on Indian government for not providing adequate patent protection to multinational drug companies. In its decision, the patent office held that Boehringer failed to establish any technical advancement or any economic significance for the compound, and the monohydrate crystal form also fails to demonstrate any new therapeutic efficacy and therefore cannot fulfill the requirement of a patentable invention under Section 3(d) of the Patents Act.

Facts and highlights of the case:

  • Boehringer Ingelheim filed a patent application (558/DELNP/2003) for crystalline tiotropium bromide monohydrate in Patent Office, Delhi on 16th April, 2003.
  • A pre-grant opposition was filed by Intermed Labs Pvt. Limited on 05th November, 2007 against the grant of this patent application. The said pre-grant opposition was heard by the then Learned Controller Mr. S.K.Roy. However, the application was recommended for Grant of the Patent on 21st December, 2012 and was allotted the Patent No. IN254813.
  • CIPLA filed a post-grant opposition to Boehringer’s patent, claiming the drug was ‘obvious’, and the crystalline tiotropium bromide monohydrate did not demonstrate any significant change in ‘therapeutic efficacy’.
  • Indian Patent office issued an order on March 2015 to revoke the Boehringer’s patent (IN 254813) covering crystalline tiotropium bromide monohydrate.

This is considered as a landmark case as the patent was revoked after it was granted, with much scrutiny and examination, and after the pre-grant opposition had been dismissed a few years back.

Tiotropium bromide, being a pre-1995 molecule, was not patented in India as the Indian patent law did not provide patent protection for “products” till 1995. However, Boehringer filed a patent application for the crystalline tiotropium bromide monohydrate on the grounds that the monohydrate form is stable under rigorous manufacturing condition and post manufacture, and this specific form exhibits stable particle size distribution make it effective as an inhalable drug.

Cipla had filed an post-grant opposition to Boehringer’s patent in 2013, claiming the drug was ‘obvious’, and the monohydrate crystal form of tiotropium bromide did not demonstrate any significant change in ‘therapeutic efficacy’ as required under Section 3(d) of the Patents Act.

In its decision, the Patent office ordered,

            “The physical stability of the compound during formulation cannot be considered as a sole factor for improvement of therapeutic efficacy of the drug under as required under section 3 (d) of the Indian Patent Act, adding the compound is “a product of mere trial and error” and does not “involve any inventive skill”.

            “The data as submitted by the applicant relating to stability test provided in the reply statement fails to prove clearly the superior properties of the Monohydrate form in comparison with the prior art form, as stability does not have any relation with the therapeutic efficacy”, Assistant controller Ajay Thakur said.

            “In the present case, I would say that the Patentee achieved lowering of crystal growth of the active during the micronization process and such reduced particle size is effective to penetrate the lungs. But this cannot be considered to translate or exhibit enhanced therapeutic activity over the known substance “, Assistant controller Ajay Thakur said.

The Assistant controller further added that,

            “Grant of a patent in other countries cannot be cited as a proof of inventiveness, the fact as clear from the Chinese prosecution, where the Supreme People’s Court of People’s Republic of China upheld the invalidity of Boehringer’s crystalline tiotropium bromide monohydrate patent application reasoning that it lacked ‘unexpected technical effects’ and hence was not ‘creative'”.

Cipla (an Indian Pharma major) has been marketing the generic version of tiotropium bromide monohydrate under the brand name “Tiova” since 2003. The revocation of the patent paves the way for the Indian firm to continue selling its generic version in the Indian market.

Boehringer Ingelheim has a three month window to appeal to the Intellectual Property Appellate Board to seek a review on the order issued by the patent office.

The Section 3(d) was incorporated in the amended Patent Act with the objective of blocking the pharmaceutical companies’ attempt to claim patent right for incremental innovation involving new forms of a known molecule with no significantly enhanced efficacy. MNCs have been constantly trying to circumvent this provision ever since the Patent Act was amended in 2005. In view of the Public interest, the Indian government does not want pharmaceutical companies to unjustifiably profiteer from pharmaceutical substances that involve only incremental innovation.

About the Author: Antony David, Senior Patent Associate at Khurana & Khurana, Advocates and IP Attorneys and can be reached at: antony@khuranaandkhurana.com

Recent decision of Delhi High Court in the case of GILEAD PHARMASSET, LLC V. UNION OF INDIA & ANR

Recently, the Delhi high court on dated 30th January 2015 set aside an order of the Deputy Controller of Patents and Designs. The impugned order rejected a patent to US drug maker Gilead for its hepatitis C drug “Sovaldi” on dated 13th January 2015. The detailed judgment can be found here.

Facts of the case:

M/S GILEAD PHARMASSET, INC, USA, filed a patent application on 30/05/2003 in USA and the corresponding application was filed in India through PCT on 27/12/2005 vide application no. 6087/DELNP/2005 (“A (2’R)-2′-DEOXY-2’FLUORO-2′-C-METHYL NUCLEOSIDE”). Two Entities, NATCO Pharma Ltd. and Delhi Network of Positive People +IMAK filed applications for pre-grant opposition, under Section 25 of the Act on dated 13 March 2014 and 17 March 2014 respectively. On 13th January 2015, the Patent Office rejected Gilead’s Hepatitis C drug, sofosbuvir (Sovaldi) on the basis of it failing to clear Section 3(d) of Indian patent act 1970 which prevents evergreening of patents and provides that no new form of an existing substance shall be patented unless the new form is more effective than the old one. The copy of the decision made by Controller General of Patents can be accessed here.  Being aggrieved by the order, the GILEAD filed the present writ petition under Article 226 of the Constitution of India.

Arguments advanced by the petitioner:

It was argued by the Counsel for the applicant that while passing the impugned order, Indian Patent Office (IPO) had taken recourse to the material and objections, which were placed on record by the applicants, who had filed their applications to oppose the grant of patent to the petitioner, under Section 25 of the Act. Further it was submitted that this aspect, was clearly demonstrable from the fact that, not only the grounds taken in opposition and documents cited were considered, while passing the impugned order, but even, the typographical errors contained in the applications, filed under Section 25 of the Act, got incorporated in the said order.

It was further contended that the once notice was issued to the petitioner for a hearing under Section 14 of the Act, to consider, whether to grant a patent as requested, IPO should also have heard the petitioner regarding objections raised in the application, under Section 25 of the Act. The learned counsel contended that, while documents in opposition filed by the entities, which had preferred applications under Section 25 of the Act were supplied, no opportunity, was given, to meet the objections raised by them.

Further it was submitted that the impugned order, had created a peculiar situation whereby, while it had returned a finding that the claims presented by the petitioner represented “novelty and inventive steps”, it sustained, the challenge, under Section 3 (d) of the Act, though the applicants, which had opposed grant of patent, had raised objections, on both counts.

Arguments advanced by the Respondent

On the other hand, the opponent contended that the exercise carried out by IPO under Section 14 and 15 of the Indian Patent Act, is quite different, from that, which IPO carries out while hearing applications filed under Section 25 of the Act. Further it was submitted that, while the material and/or objections filed by opponents, which had preferred applications under Section 25 of the Act, was supplied to the petitioner, IPO did not rely upon the same, while passing the impugned order.

Decision of the Hon’ble Court:

The hon’ble court observed that while petitioner’s request for a hearing under Section 14 of the Act was pending, two pre-grant oppositions were filed. Though, the documents filed by the opponents were supplied to the petitioner, no notice was issued to the petitioner with regard to the applications filed under Section 25 of the Act. Therefore, when hearing under Section 14 was finally granted to the petitioner on 24.07.2014, there was no clarity as to the extent and scope of objections, which it was required to meet while pressing ahead with its request for grant of patent. The petitioner, at best, would have prepared itself to rebut the objections raised in the FER. Further the court observed that combining S. 25 and the S. 14 proceedings, if Gilead would have been given an opportunity to be heard on both counts, it could have save not only time, effort but also have avoided the allegation of bias.

 The court accepted the Gilead’s claim and set aside the impugned order given by IPO and remanded for a fresh decision. The court also ordered IPO to fix a date of hearing both for Sections 14 and 25 proceedings and asked to send written communication to all concerned parties including the petitioner.

 Thus it would be interesting to see the decision by IPO after fresh consideration to the facts and circumstances in view of the fact that Gilead has already entered into license agreements with Generic companies of India for the drug “Sovaldi” as per the reported news in September 2014.

About the Author: Mr Sitanshu Singh, Patent Associate at Khurana & Khurana, Advocates and IP Attorneys and can be reached at:Sitanshu@khuranaandkhurana.com