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Delhi High Court Upholds Roche’s Patent Claims on Lung Cancer Drug (Tarceva) against Cipla

A division bench of Delhi High Court on 27th Nov 2015 held that the Indian drug manufacturer Cipla infringed Swiss pharmaceutical company Roche’s patent on Erlotinib hydrochloride, marketed under the name of “Tarceva”.

Roche was granted a patent in India on Erlotinib hydrochloride (Tarceva) in 2007. Roche sued Cipla for patent infringement in January 2008 soon after Cipla announced its intent to launch a generic version of Erlotinib (i.e. Erlocip) at Rs.1,600 per tablet, compared to Roche’s selling price of Rs.4,800 per tablet.

The verdict came on the pleas of Cipla and Roche, both of which had challenged the single judge’s order of September 7, 2012. The single judge in his order had held that Cipla was not infringing Roche’s patent and refused to grant any injunction against Cipla, and it allowed the Indian drug firm to continue selling its generic product, Erlocip. The judge had also refused to revoke the patent of the Swiss company as sought by Cipla.

A division bench of justices Pradeep Nandrajog and Justice Mukta Gupta held that the single judge “erroneously compared the products of Roche and Cipla when he ought to have mapped the claims of the suit patent against Cipla’s product”.

Cipla in its plea had urged that while the patent sought to be enforced was for polymorphs A+B of Erlotinib hydrochloride, the product under manufacture by both Roche and Cipla was polymorph B, which ought to be assumed to be in the public domain and, hence, the Indian company’s activities were non-infringing in nature.

Roche in its plea had contended that the basic patent was not confined to any polymorphic form of Erlotinib hydrochloride and, hence, as long as the compound was present in Cipla’s product Erlocip, it infringes the patent.

The division bench in its decision held that:

“This (the patent claim) is a sufficiently broad claim that is clearly not limited to any polymorphic version of erlotinib hydrochloride, but to erlotinib hydrochloride itself,”. “This compound may exist in several polymorphic forms, but any and all such forms will be subsumed within this patent. Therefore as Cipla’s Erlocip is admittedly one particular polymorphic form of the Erlotinib Hydrochloride compound (Polymorph B), it will clearly infringe IN’774 patent.”

The court, however, refused to issue any injunction against Cipla restraining it from manufacturing the medicine, after observing that the life of the patent granted to Roche was ending in March 2016. However, the Court has directed Cipla to render accounts to Roche and make payment for the patent infringement.

“…keeping in view the fact that the life of the patent in favour of Roche in India would expire in March, 2016 we do not grant the injunction as prayed for by Roche against Cipla (because as noted above there was no interim injunction in favour of Roche and due to said reason Cipla continued to manufacture and sell Erlocip),” held court.

Also, the division bench in its 106-page judgment said that as Cipla “could not establish prima facie that the suit patent was obvious”, its plea for invalidating Roche’s patent on the ground of ‘obviousness’, “fails”. In addition, Cipla had demanded Roche’s patent be revoked under Section 3(d) of the Indian Patent Act that essentially bars incremental innovations unless significant efficacy is proven.

Bringing clarity to Section 3(d), the judges wrote: “We understand Section 3(d) as a positive provision that in fact recognizes incremental innovation while cautioning that the incremental steps may sometimes be so little that the resultant product is no different from the original. The inherent assumption in this is that infringement of the resultant product would therefore be an infringement of the original i.e. the known substance and by no stretch of imagination can Section 3(d) be interpret as constituting a defence to infringement.”

Roche welcomed the decision of the Court which upheld the patent covering Erlotinib hydrochloride (Tarceva) and found Cipla to have infringed it.

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


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

CIPLA & BMS may settle patent dispute over Entecavir in India

US based pharma major Bristol-Myers Squibb (BMS) and Indian pharma company Cipla Ltd. are heading towards an amicable settlement on a long-stretched patent dispute concerning BMS’ hepatitis B drug Entecavir, a leading anti-viral drug for Hepatitis B patients that brings in more than a billion dollars each year globally for BMS.

Entecavir, 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, BMS filed a patent application for its once daily composition comprising Entecavir and got a patent in India for the same. The patent application (IN/PCT/2002/00891/MUM) was filed at Mumbai patent office by BMS in 2001 and it was granted (IN213457) in the year 2008.

Claim 1 of IN ‘457 read as:

  1. A pharmaceutical composition effective for once a day oral administration to treat Hepatitis B virus infection in a human adult patient comprising up to 1 % of entecavir, adhered to a carrier substrate of kind such as herein described, and pharmaceutically acceptable excipients such as herein described in an amount as herein described, wherein the said percentage is based on a total composition weight of 100 mg.

Claim 12 of IN ‘457 read as:

  1. A method of preparing a pharmaceutical composition of entecavir as claimed in claim 1 comprising (a) dissolving said entecavir and an adhesive substance in a solvent wherein said solvent is water or water having an acidic or basic pH, (b) spraying said solution obtained in step (a) onto a carrier substrate while said carrier substrate is in motion, (c) drying said coated carrier substrate from step (b) to remove said solvent, and (d) combining said dried coated carrier substrate from step (c) with other excepients as claimed herein above to form said pharmaceutical composition.

In 2010, Cipla, had filed a revocation application with the India’s Intellectual Property Appellate Board (IPAB) against BMS’ patent IN ‘457 covering a pharmaceutical composition comprising up to 1% of Entecavir effective for once a day oral administration to treat Hepatitis B virus infection in a human adult patient.

When the case came up before the IPAB, the counsel representing Bristol-Myers Squibb informed the patent tribunal that both the drug makers are in negotiations to settle the patent dispute. The IPAB bench comprising chairman justice KN Basha and DPS Parmar, technical member, patents, adjourned the matter since both the parties were exploring the possibilities of an amicable settlement.

BMS previously reached a settlement with Indian generic firm Natco Pharma concerning the drug. Natco and BMS had entered into a similar settlement over the Entecavir composition patent, after Natco had applied for revocation of the patent at the IPAB.

Generic drug producers such as Dr. Reddy’s and Cadila launched their generic versions of Entecavir (Baraclude) in India earlier in 2010 by designing around the once daily composition patent. Ranbaxy had also launched a generic product of the drug earlier in the Indian market.

US scenario of Entecavir: (Patent dispute between BMS & Teva)

Entecavir is protected by two patents in United States viz. US 5206244, product patent which covers the Entecavir molecule and US 6627224 which covers Entecavir compositions effective for once a day oral administration. Teva Pharmaceutical, an Isreal based generics major, challenged the Entecavir product patent in a US court and launched its generic version of Entecavir in US market. Teva successfully invalidated the Entecavir product patent based on obviousness ground and an appeal by BMS was denied by the US Court of Appeals for the Federal Circuit, in 2014.

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

News Snippet: Novartis sues Cipla for infringement of patents covering “Onbrez”

In a latest update, Novartis has sued Cipla for infringing its patents on “Onbrez” (Indacaterol) after Cipla lunched its generic version for Indacaterol in October claiming “urgent unmet need” for the drug in India.

Earlier, as we have reported here, Cipla approached Govt. of India to exercise its statutory powers to revoke the five patents covering Indacaterol granted to Novartis, which is yet to be decided.

Novartis requested high court to permanently restrain Cipla from manufacturing Indacaterol in any form and selling it in India. It also sought damages for infringing the five Indian patents covering Onbrez.. In reply, Cipla contended that “Onbrez” sold by Novartis is too expensive and is not easily available to the public. Delhi High Court has reserved its verdict on January 9 after hearing detailed arguments by both parties.

CIPLA’s plea for revocation of Novartis Patents for Onbrez may face major set back by the Government

As reported in TOI, the Indian Government has found very little merit in Cipla’s plea for waiver and cancellation of Patent rights for chronic obstructive pulmonary disease (COPD) drug over which Novartis has exclusive rights. We have reported on Cipla’s plea here.


Cipla, previously approached the Department of Industrial Policy and Promotion (DIPP) to exercise its statutory powers under Section 66 and Section 92 (3) to revoke Indian Patents IN222346, IN230049, IN210047, IN230312 and IN214320 granted to Novartis AG for the drug Indacaterol and is currently selling under the brand name Onbrez. The said drug is one of the preferred medications for COPD.

The relevant sections 66 and 92 of the Indian Patents Act are as follows:

  1. Revocation under section 66:

Section 66 states “Where the Central Government is of opinion that a patent or the mode in which it is exercised is mischievous to the State or generally prejudicial to the public, it may, after giving the patentee an opportunity to be heard, make a declaration to that effect in the Official Gazette and thereupon the patent shall be deemed to be revoked”.

  1. Special provision for compulsory licences on notifications by Central Government

Section 92 (3) states Notwithstanding anything contained in sub-section (2), where the Controller is satisfied on consideration of the application referred to in clause (i) of sub-section (1) that it is necessary in—

(i) a circumstance of national emergency; or

(ii) a circumstance of extreme urgency; or

(iii) a case of public non-commercial use,

which may arise or is required, as the case may be, including public health crises, relating to Acquired Immuno Deficiency Syndrome, Human Immuno Deficiency Virus, tuberculosis, malaria or other epidemics, he shall not apply any procedure specified in section 87 in relation to that application for grant of licence under this section:

 Provided that the Controller shall, as soon as may be practicable, inform the patentee of the patent relating to the application for such non-application of section 87.”

Cipla’s Contention in the Representation:

  • Cipla argued that the causes of COPD are several and the sheer magnitude of the disease as per the publicly available data which is sufficient for the Central Government to invoke the provisions of Section 92 and to treat it as an “epidemic” or a “public health crisis”. Such exercise of power in the present case would be in consonance with the avowed purpose for which Section 92 has been enacted.
  • Cipla also contended that Novartis has been granted these patents since 2008-09 but has chosen not to manufacture the same in India. However, Novartis merely imports a negligible quantity of these products manufactured in Switzerland through its licensee Lupin Pharma as per its own data filed before the Patent office. As submitted by Novartis in IPO in Form 27, the import for the year 2013 is a meagre 53,844 units which do not satisfy even 4,500 patients annually which is a shortage is more than 99.97 percent.
  • Further Cipla contended that cost of the drug is also very high for a patient in India. The estimated cost of the drug Indacaterol as imported and sold by Lupin Limited, under the trademark Onbrez is about Rs.2000/- per month per patient. On the contrary, the proposed drug of Cipla under name UNIBREZ would be costing approximately Rs. 400 per month.

 It is pertinent to note that Section 66 has been invoked only on two occasions earlier. Firstly it was invoked for the case of a process patent granted to Agracetus, an American company for genetically engineered cotton cell lines. The said patent was revoked by the Central Government in the year 1994 keeping in mind public interest and the fact that genetically engineered cotton, being a product of concern for the national economy, particularly for agriculturists, ought not to be the subject matter of a patent monopoly. Secondly in 2012, a patent granted to Avesthagan Limited for a “synergistic ayurvedic/ functional food bioactive composition” i.e. the composition consisting of Jamun, Lavangpatti and Chandan to be used for treatment of Diabetes. In light of the public interest in using traditional knowledge for curing and treating Diabetes, the said patent was also revoked under Section 66 of the Act. However pertinently, both the patents were revoked due to cloud over patentable subject matter.

It would be prejudiced to comment on the fate of the matter at this stage. However as per TOI the Govt. may turn down the plea of Cipla for revocation of Novartis patent.

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

Cipla Files Representation with Govt. Seeking Revocation of Novartis’ Patents

It has been recently reported in Economic times that Cipla has filed representation with the government (Department of Industrial Policy & Promotion) seeking revocation of five patents of Novartis on indacaterol, a respiratory drug for the treatment of chronic obstructive pulmonary disease (COPD) and marketed as Onbrez by Novartis. The central government, under section 66 of the Indian Patent Act, has the power to revoke patent in public interest, after giving patentee an opportunity to be heard.

According to section 66,

“Where the Central Government is of opinion that a patent or the mode in which it is exercised is mischievous to the State or generally prejudicial to the public, it may, after giving the patentee an opportunity to be heard, make a declaration to that effect in the Official Gazette and thereupon the patent shall be deemed to be revoked.”

Cipla has launched its generic version of indacaterol and alleged that Novartis held patents on indacaterol since 2008-09 without manufacturing in India and importing only in negligible amounts, as a result of which there is an urgent and unmet need to provide this drug to patients at affordable prices. According to Cipla, it has potential to manufacture adequate quantities of the drug to make available in the country.  Cipla’s launched generic version of indaceterol is reported to be 1/5th of the price of Novartis’ Onbrez.

This is the first time that an Indian generic company has asked the government to revoke patents on the ground of public interest under section 66. Otherwise, the revocation has always been sought on grounds under section 64 (for example obviousness, anticipation, insufficient disclosure, violation of section 8, 3d etc.), whether an Indian company has filed a revocation petition or a counter claim in an infringement suit. However, public health and drug price play significant role in deciding a patent’s fate in India especially in context of Compulsory Licensing of patent as it happened in Natco’s case. Even in Roche v. Cipla, public health and pricing issues were considered by the India courts, although the decision at the High Court was based on merits of the case and not in public interest.

It is highly expected that Novartis will take a legal course to challenge Cipla’s launch. Novartis has been very active to protect patents for its one of the blockbuster anti-diabetic drugs vildaglipton in India. Novartis has sought, just a few months ago, quia timet interim injunctions against several Indian generic companies including Glenmark generics, Bajaj healthcare, Cadila healthcare, Alembic pharmaceuticals against alleged patent infringement of vildaglipton even before they actually launched their generic versions and after they obtained marketing approvals from DCGI.

Thus Novartis will most likely file patent infringement suits seeking interim/permanent injunctions restraining Cipla from manufacturing and selling generic version of indacaterol in India.

On another note, Cipla could also have applied to obtain a compulsory license to manufacture and sell indacaterol before launching the drug. All three grounds of granting compulsory license under section 84(1) viz. reasonable requirements of public not being met, drug non-affordability and non-working of patent in India could have been proved by Cipla. According to Cipla, Novartis declared import of meagre 53,844 units for the year 2013 which do not satisfy even 4500 patients annually where there are more than 1.5 crore patients in need of the drug. Cipla also urged the government to consider COPD as an epidemic worthy of being qualified as a “public health crisis” as it claims 50 lakh lives annually in India, which is more than the toll from HIV-AIDS, malaria, cancer and tuberculosis.

Till now, we are not aware of any case in India wherein the government has revoked the patent in public interest under section 66. The outcome of government opinion to revoke said patents is thus eagerly awaited. This would act as precedent for all similar future cases. And if the government decides to revoke the patent under this section, the ongoing conflict between multinational innovator companies and Indian generic companies is going to intensify. Innovator companies criticize that India has weak patent laws not in compliance with international standards, whereas Indian government takes a stand that its patent laws are in compliance with TRIPs standards and are designed to meet the objectives of drug availability, affordability and accessibility.

 About the Author: Meenakshi Khurana, Partner at Khurana & Khurana, Advocates and IP Attorneys and can be reached at: meenakshi@khuranaandkhurana.com

Smart Strategizing – Protection by shielding through Patent Evergreening in Pharmaceutical Domain with special reference to Roche v Cipla

Pankaj Mohanta, an intern at Khurana and Khurana talks about patent evergreening in the pharmaceutical domain. Through this post, he gives special emphasis on the recent landmark case of Roche v Cipla, which created quite a stir in the pharmaceutical industry.

Needless to say, patent evergreening is that territory which falls in a bit of a grey area. With the recent criticisms and mushroom cloud of controversies surrounding this topic has forced the pharmaceutical companies to sweep this method piece under carpet. But perceiving the high value returns in this era of uncertainty with an insight to step a foot into the future, taking chances doesn’t really seem that compromising given the fact that colossal figures have been continually pumped into the R&D departments. The pretty recent patent litigation of Roche v Cipla was one of a kind, where the world got to have the opportunity to witness a one of a kind, call it legal or business strategy. The plaintiff here who happened to be Roche, attempted prohibiting the defendant company Cipla from manufacturing the former’s anti-cancer drug formulation – Erlotinib. This drug’s generic equivalent costs the 1/3rd the amount of the protected and patented drug formulation available as, over the counter antidote in the markets, thereby running the risk of relatively less adoption or possibly, rejection by the consumers. The plaintiff then sought an interim injunction against the defendants. But the prime hassle arose with the morphed or an altered substitute, here in this case, a Polymorphic Form B belonging from the same class of drug but wasn’t one of Roche’s patented drug, thereby rendering the court to decide in favor of the defendant along with the light of the provision mentioned in the leading statute of Section 3 [d] of the Indian Patents Act, 1970 following a stance that Cipla didn’t infringe Roche’s Indian Patent IN 196774.

The key focus at the heart of any pharmaceutical giant’s agenda, which produces patented drugs on a mass commercial scale is to incentivize and widen its sphere of operability by way of a selective monopolization driven at a speed in order to achieve a protective perpetuation for any given drug formulation of its origin. So, if we speak of a way to safeguard a prolonged scalability for pharmaceutical companies, they might consider patent evergreening as one of those techniques for future medicine which would potentially drive an evolution of smart grid initiatives ushering in a new era of pharmaceutical dynamics paving way for a paradigm shift the way pharmacokinetics, patient healing and enhanced frugality as a viable turnover alternatives interact in the health landscape.

Patent Evergreening – What and how this stuff works?

It is a term which implies a step that aims for perpetuation of a protection over a given patented drug. To be a bit comprehensive on this part, I mean a technique which describes a latency requirement which is often exercised as a strategy by assistance of which pharmaceutical players with patents involving certain drug formulations which are about to hit expiry date tacitly hold the incentive returns from those antidotes by aggressive takeover or buying out their threats or in this case, their competitors or by taking out new patents which are closely associated with the existing ones by working around their innovation and or working out on a formulation having a stark contrast with that of the existing ones effectively devising a new pharmaceutical mixture.

However, this practice may not have gone that mainstream in a given spectrum of priorities of the pharmaceutical companies in the current scenario. But, a matter of fact, having achieved high net returns when there is too much of time and money at stake, this stream definitely demands privileges in intellectual monopolies for which the pharmaceutical companies would just do whatever it takes for them to grab hold of this appealing platform despite an inherent risk of regulations powered by various statutes and bodies that makes sure that a level of hybrid governance is being taken care in this sector. Be it jurisdiction to prescribe, adjudicate or to enforce, it has been sort of a taboo for jurists to openly express about this whilst patent litigations. Here, however, no active patent ingredient over a drug composition is being taken into consideration instead the delivery channels and its general usage.

In this post, I would further focus on the peculiar grey area of patent evergreening which can effectively be crafted as a smart strategy which could potentially be an element in the pharmaceutical domain, for sizing, shaping and seizing the future. However, if the pharmaceutical terrain is mapped for competitiveness, even they are subjected to few conditions of which the companies need to comply and work along, lest to avoid an opportunity paradox and they are: generic arm patents of their own organization and re-inventing around a patented drug that are soon to expire.

Exhibit A – Pharmacogenomics

Object – Apply in a view to looking for extension of protection of the soon to expire patent by patenting a formulation which is established by evidence based facts [both clinical and lab] to prove its efficacy in functioning and delivering results.

This is an eclectic combination of Pharmacology and Genomics. This concept is pretty futuristic and relatively new in application where it aims to arrive at a certain component having desired results whilst customized and tailored to a patient’s genetic makeup.  Variant factors are responsible for a peculiarity of drug responsiveness in a given physiology of a patient’s system which may be affected by lifestyle, age, diet, environment etc. but hitting a factor that remains largely constant which includes a patient’s genetic set up can lead to instantly affirmative, uniform and scalable results with a bonus package of safety and greater efficacy.

The following positive drivers shall tentatively enable the pharmaceutical companies to be at vantage point over others those practice the traditional way & some of those drivers are:

  • Enhanced Medications
  • Safer Drugs
  • Achieving accuracy in drug delivery dosage administration
  • Advanced screening for pathophysiology
  • Re-engineered Vaccines
  • Stable Performance
  • Better chances of approval
  • Plummet in the expenses for health care

Exhibit B – Data Exclusivity

Object – Apply in a view to looking for extension of protection by way of excluding generic drug manufacturing companies from the data devising methodologies which has value of efficacy, safety and quality that gives a formulation an edge over the existing traditional drugs which are protected and are soon to expire.

Article 39.3 of the Agreement on Trade Related Aspects of Intellectual Property Rights recognizes the need to have an IP regime for protection of test data and analytical insights in the pharmaceutical sectors where the patent protection as a standalone guarding statutes or combination of such regulatory statutes. The data exclusivity evergreening is that form of protection that has the capacity to, in fact, restricting the governments for prohibiting a grant for a compulsory license on patented drugs as the monopoly would anyway prevent other pharmaceutical companies for marketing the generic products. Well, rest assured, this stays as one of the reliable methods for protection while the industry giants sought test data exclusivity in Free Trade Agreements and try fixing it by provisos with their trade counterparts. The European Union by far, has been most friendly to the pharmaceutical players with the maximum protection period of Eight years with an additional Two years of market exclusivity.

Exhibit C – Supragenerics

Object – Apply in a view to looking for extension of protection by innovations which have the feasibility of being patentable by altering them into an enhanced form of the pre-existing products that are soon to expire of that company and release into the over the counter stores in a bit advance.

Hence, the players can attempt in releasing the oxygen by implementing and deploying those above mentioned techniques which are some of the smart strategies, a pharmaceutical company can chalk out in order to hit those guaranteed sweet spots in their domain. By reinventing their offer with a continuous focus on their patent portfolio while keeping a hawk’s eye over the prevalent regulation and compliance, they can effectively secure their valuable market share and yet manage to retain their customers by driving better pharmacological patient centricity.

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Roche v Cipla: Part 2: Infringement

In continuation of the last piece over here, let’s now discuss the actual issue of infringement of IN ‘774 patent by Cipla crisply. My apologies for a long delay in writing this piece due to long travelling schedule and back-to-back heavy projects thereafter. Nevertheless, it is better to be late than never. Here it goes.

The claim 1 of IN’774 is read as:

1. A novel [6,7-bis(2-methoxyethoxy)quinazolin-4-yl]-(3-ethynylphenyl)amine hydrochloride compound of the formula A [structure]

The defendant raised several defences resisting the infringement of this claim. The defendant provided an X ray diffraction of Tarceva and concluded that the drug is actually the Polymorphic Form B and that the features of Polymorph B contained in Tarceva corresponds with the US patent 221.

Further the defendant argued that the tablet of Erlotinib Hydrochloride cannot be made by way of simply following IN’774 rather the patent US‘221 is relevant for the same purpose and this shows that there is further process of reaction of the compound of  IN’774 with that of other constituents in order to arrive at Polymorphic version. The suit patent compound is thus not automatically leading to Polymorphic version.

Roche then argued that Claim 1 of the suit patent is for the Erlotinib Hydrochloride per se, and not restricted to any particular Polymorphic form or mixture of any forms, nor claims any particular Polymorphic form and that the Active Pharmaceutical Ingredient in the Defendant‘s product Erlocip is also Erlotinib hydrochloride. Roche submitted that the defendant could not have arrived at Polymorph B form without crossing the stage of preparation of combination Polymorph A and B and therefore, the defendant product even if the same is a Polymorphic Form B of the molecule would still infringe IN‘ 774.

Cipla’s main point of argument was that the separate patent applications were filed in India (IN’507) and US (US’221) for Polymorph form B and Erlotinib Hydrochloride and that clear admissions have been made that IN’774 relates to Polymorph A+B and the second patent US‘221 and corresponding application in India IN’507 relates to Polymorph B of Erlotinib Hydrochloride. According to Cipla, if Roche filed a fresh patent on Polymorph B, they themselves believed that Polymorphic version is distinct from that of the main compound and when IN’507is rejected by the Indian Patent Office, they took a U-turn and argued that the somersault and are arguing that the second product is covered by the first patent.

The judge followed the purpotive rule of construction of the patent claim,

whether the patent claim subsumes the product or the process impugned is a matter to be examined from the standpoint as to whether the patentee could have reasonably included the said product or process in question which is he is impugning on the fair reading of the invention

According to the Judge there are some of the facts which should have been deposed by Plaintiff in order to show that there is an infringement done by the defendant by manufacturing the Polymorphic version B which is covered in the main compound. Some of those main facts are:

  • How many reactants or variants with which the main Erlotinib compound is reacted with in order to arrive at the Polymorphic Form B of?
  • Whether the properties and the characteristics of the main compound changes or varies after the said reactants or variants are reacted with or not. The plaintiff in order to show that there is an infringement should have deposed to the effect that the said properties and characteristics are not changed pursuant to the reaction.

However, the plaintiff had not been able to show as to what is the exact nature of the plaintiff and defendant products which are being sold in the market, further, whether the said products corresponds exactly with the claim of the suit patent is also not established, among other facts.

On the other hand, the defendant was able to show that the plaintiff’s suit compound is a combination of A and B and the compound needs to be converted or separated in order to arrive at the Polymorphic version B. Plaintiff argued that the plaintiffs‘ suit compound is not separated but converted, to which Judge remarked that,

Whether the said compound is covered or separated, the moot question is that there is something which is done besides the compound as contained in the suit patent in order to arrive at Polymorphic B. if the answer is in affirmative, I think, the onus is discharged”.

The issue is accordingly decided in favour of the defendant and the suit and the counter claim were dismissed.


Thus, in the Indian geography, after the patent on the main compound is obtained, firstly it is extremely difficult to get a subsequent selection patent on polymorph (or other forms) on ground of Section 3d and secondly and importantly the marketed drug based on polymorphic form would easily be prone to generic competition without infringement of the main patent.

About the Author: Meenakshi Khurana, Patent Attorney, available at meenakshi@khuranaandkhurana.com

Roche v Cipla: Part 1: Validity of Patent

In continuation of our previous post here, and following the availability of the 275 page judgement, we would discuss herein the various facets of the case and discuss one by one. This case actually involved two main issues as follows,

Issue I. Whether Roche’s Indian Patent 196774 is invalid (liable to be revoked under S. 64);

Issue II.  Whether Cipla’s manufacturing, marketing and sale of Erlocip infringes the Patent IN196774

Let’s first discuss the issue of the validity of the IN’774 patent (which runs up to 181 pages of the judgement!)

The defendant (Cipla) prayed for revocation of the IN‘774  patent by way of counter claim on the grounds mentioned in S. 64 of the Indian Patent Act, namely, obviousness (lack of inventive step), anticipation by prior publication and prior claim, insufficient disclosure, false representation, violation of section 8 and section 3(d).

Out of these, the obviousness ground was discussed and argued in detail by Defendant and Plaintiff.


According to Cipla, arriving at the IN‘774 patent is obvious to the person skilled in the art.  The structure of Erlotinib Hydrochloride as claimed in IN‘774 is:



And the structure of the compound identified as ‘Lead Compound’ by Cipla for their arguments on obviousness analysis is the one disclosed in EP’0566226 (‘226 patent) is:

EP‘226 patent: Example 51


EP‘226 patent: Example 51

Cipla contended that substitution of methyl group with ethynyl group at the third meta position would be obvious to a person skilled in the art.

The following points were main points of discussion:

  1. Selection of Lead Compound: Whether Example 51 is the Lead Compound or not?
  2. Motivation to substitute at 3 prime position
  3. Interchangeability of methyl and ethynly groups

1. Selection of Lead Compound: Whether Example 51 is the Lead Compound or not?

Cipla’s contentions:

  • Cipla contended that there is sufficient motivation to do further R&D in the preferred compounds disclosed in EP‘226(patent which is an admitted prior art in the complete specification of suit patent) which discloses a class of quinazoline derivatives having anti-cancer properties.
  • The compounds disclosed in EP‘226 are compounds which are obvious to try permutations and combinations on.
  • EP‘226 discloses 3 preferred compounds amongst which one is example 51 which is the closest prior art.

Roche contentions:

Roche very rightly contended that Cipla has not explained as to how the said EP‘226 will act as a motivation towards arriving at the suit patent invention. Following are some of the main arguments by Roche:

  • Cipla only relied upon the prior arts stated by Roche in their own patent ‘774 patent, all of which disclose -4-anilinoquinazoline derivative compounds possessing anti-cancer properties. Each of these prior arts, EP‘722, EP‘226, EP‘851, EP‘507, and EP‘498 have same core structure and are represented by Markush Structure thus encompassing millions of compounds.
  • The compounds tested in prior arts EP‘722, EP‘851, EP‘507, and EP‘498 were found to have better or similar IC50 values as compared to compounds in EP‘226. The person skilled in the art will in particular look at Example 2(5), disclosed in the EP‘851 which has the IC50 value of 1nm.( Lower the IC50 value, more potent is the drug)
  • Cipla has provided absolutely no evidence to show why EP’226 is the starting prior art as opposed to EP’851. Cipla has selected Example 51 with full knowledge of the structure of Erlotinib Hydrochloride, i.e. the defendant has selected Example 51 as the lead compound purely on the basis of hindsight.
  • EP‘226 discloses 80 examples providing 102 specific exemplified compounds, 32 specifically preferred compounds, 18 claimed compounds and five prominent compounds for which specific IC50 values are given. Example 51 does not feature amongst the five prominent compounds mentioned in EP‘226 for which IC50 value have been provided. Therefore, there is no teaching, suggestion or motivation in EP‘226, regarding any useful properties or potent and promising activity to select Example 51 as the lead compound.

2. Substitution at 3 prime position

Cipla’s contentions: Cipla provides evidence to show that substitution at the third meta position of example 51 can be tried and made following the concept of Bio-isosterism.

Roche’s contentions: Roche contended thatout of all the available substitutions, methyl is kept constant in 3’ position in 80% of the prominent compounds for which specific IC50 values are given and thus the teachings of EP‘226 direct a person skilled in the art that 3’-Methyl should be left undisturbed for good biological activity.

3. Interchangeability of methyl and ethynly groups

Cipla’s contentions

Cipla contended that methyl and ethynyl are interchangeable due to: Bio-isosterism; and Interchangeability of methyl with ethynyl in light of prior arts US’590; EP’700; US’766; US’534.

Roche’s contentions

3’-position in Markush structure (R2) in EP’226 patent stands for 45 different substituents. There is no teaching provided that a person skilled in the art will substitute methyl with only Cyano group and not other 43 substituents as none of the 32 specific preferred compounds include the Cyano substitution.

As far as five prior arts were concerned, Roche contended that these could not be taken into record as they were not disclosed prior to the filing of the Replication to the Counter Claim.

Further Roche contended that of these five patent documents, US’766 and US’534 are not even valid prior arts under Section 64(1)(f) because they were published subsequent to the priority date of the ‘774 patent.

Judge’s Remarks on obviousness

Justice Manmohan Singh rightfully concluded that on the basis of evidence by defendant (Cipla) to establish obviousness, no ground of obviousness is made out under S. 64(1)(f).


The onus was on the defendant (Cipla) again to show as to how the plaintiff‘s (Roche’s) compound of Erlotinib Hydrochloride is a new form of known substance.

According to Cipla, Erlotinib is a derivative of Quinazoline, which is known for its anti-cancer activity with no enhanced activity and hence is hit by S. 3(d).

Plaintiff contended that “Quinazoline Derivatives” is a wide class of compounds having diverse uses including non-pharma uses and Erlotinib compound is just one specific compound of this family. Thus merely the term “Quinazoline Derivatives” does not infer that the Erlotinib compound is a derivative (new form) of the known substance.

Roche also provided evidence to show efficacy by way of clinical trials and thus according to Roche even if the said derivative Ertolinib is found to be one of the forms of the EP‘226 patent, still the same being efficacious cannot be presumed to be same substance under Section 3(d). However it could not be proven during cross examination of the expert witness that whether the clinical trials were conducted on the polymorphic form b (which is the marketed product Tarceva) or the Erlotinib compound (comprising both Polymorphic A and B).

The Judge concluded that since Defendant failed to give evidence that Erlotinib compound is a new form of known substance, the ‘774 is not hit by S. 3(d).


A crisp summary of the discussion on this ground is provided herein. The few points are worth mentioning:

1. The IN’774 patent: filed on 13.3.1996; claims combination of polymorph A and B; granted in 2006.

2. The IN’507 application: filed on 1.6.2006; claims polymorphic B version of Erlotinib compound (and which is the marketed drug under name Tarceva); rejected by Controller in 2008 in pre-grant opposition proceedings.

3. US’221 is a corresponding granted patent to IN’507; filed in 2000.

Section 8 mandates the submission of information of corresponding Foreign applications (Form 3) on “same or substantially the same” inventions relating to the Indian application during the pendency of the Indian Application. We have described requirements of Section 8 & Form 3 in detail here.

In this case, the plaintiff did not furnish Form 3 containing information of US‘221 patent. They stated that US‘221 patent is a distinct invention covering different compound. The Judge concluded that since US‘221 patent relates to “same or substantially the same” invention being the polymorphic form B of compound claimed in IN‘774 patent and hence the plaintiff was required to comply with section 8 by providing information of the same. This was the only ground of revocation which was in favour of Cipla.


Cipla presented other grounds in its counter claim too, namely

  • Ground of concealments and false representation under Section 64 (1)(j); and
  • Lack of Title/Ownership in respect of plaintiffs

After the detailed discussion on the grounds, very briefly the Judge’s findings are summed up as below:

“The defendant failed to prove that that there were concealments made in relation to the prosecution before the patent office or there is an improper examination done by the patent office. Therefore, the examination and investigation process cannot be called into question by the defendant……..The challenge on the ground of ownership title and other concealments have not been established by the defendant by not discharging the onus casted upon it. No issue was framed. No evidence was led by the defendant.”


According to Judge,

There lies a discretion in the Court to proceed to revoke or not to revoke the Patent by way of usage of term the word “may” under Section 64 of the Act.”

In the present case, only one ground namely violation of section 3 is made out. However, the inconsistency on the part of defendant and the fact that no other ground relating to the revocation of the patent is satisfied under Section 64, made the Judge to exercise discretion in favour of the plaintiff. The inconsistency of the defendant lies in that the defendant at one instance, to resist infringement, argued that the compounds in US ‘221 and IN’774 are distinct and at other instance to prove violation of Section 8, argued that they are substantially the same.

The Judge thus finally concluded the IN’774 patent to be valid.

In the second part which follows soon, we would discuss the actual issue of the infringement  of the IN’774 by Cipla in detail where the Judge observed that it was scientifically proven that Cipla’s Generic Drug is the Polymorphic Form B which is not Roche’s patented Drug and thus Cipla did not infringe said patent in India.

About the Author: Meenakshi Khurana, Patent Attorney, available at meenakshi@khuranaandkhurana.com