Drug Molecules Going Off Patent in 2010

This year at least 20 odd drug molecules will be going off-patent in the United States including (1) Merck’s anti-hypertension molecule Losartan, active ingredient of Cozaar and Hyzaar franchise, (2) Eisai’s anti-dementia molecule Donepezil, active ingredient of Aricept and Aricept ODT (3) Sanofi-Aventis’s anti-cancer molecule Docetaxel, active ingredient of Taxotere franchise, (4) Pfizer’s Latanoprost, active ingredient of Xalatan franchise, (5) Glaxo’s anti-viral molecule Lamivudine, active ingredient of Trizivir, Epivir and Combivir franchise, (6) AstraZeneca’s anti-cancer molecule Anastrozole, active ingredient of Arimidex franchise, (7) Boehringer’s anti-depressant molecule Pramipexole, active ingredient of Mirapex franchise and (8) Eli Lilly’s anti-cancer molecule Gemcitabine, active ingredient of Gemzar franchise. Novartis and Roche too are losing patent protection for their anti-viral molecule Penciclovir and antiretroviral molecule Saquinavir respectively. Other molecules losing patent protection include Cidofovir (Gilead), Imiquimod (Graceway), Naratriptan (GlaxoSmithKline), Zafirlukast (AstraZeneca), Zileuton (Critical), Topotecan (GlaxoSmithKline), Butenafine (Mylan), Adapalene (Galderma), Eprosartan (Abbott) and Tiludronate (Sanofi-Aventis).

Novartis received patent for second-line CML therapy drug

The Chennai Patent Office lately published Indian Patent No. 237430 issued to Novartis for anti-cancer drug Nilotinib, globally marketed as Tasigna. In October 2007, the United States FDA approved Nilotinib for chronic myelogenous leukaemia (CML) second-line therapy for patients who are resistant or tolerant to Imatinib Mesylate (marketed as Gleevac). The patent is granted against the mail-box Application No. 3003/CHENP/2004 claiming priority from British Application Nos. 0215676.8 and 0229893.3. We reported about Nilotinib pending patent application in early 2008 (read here). In July 2008, we also reported an advertisement by leading generic manufacturer Cipla announcing introduction of new drugs that likely included Nilotinib generic version (read here). Nilotinib belongs to the class of tyrosine kinase inhibitors. Other tyrosine kinase inhibitors that are granted patents in India include Dasatinib (IN203937 issued against the Application No. IN/PCT/2001/01138/MUM), Sunitinib (IN209251 issued against the Application No. IN/PCT/2002/00785/DEL), Lapatinib (IN221017) and Sorafenib (IN215758 issued against the Application No. 1633/MUMNP/2007). Gefitinib patent application (841/DEL/1996) was rejected by the Delhi Patent Office following pre-grant oppositions filed by Natco Pharma and JM Pharmaceuticals.

Google received Indian patent for advertising business method

Google added yet another patent in its advertising business method patent portfolio in India by protecting patent for serving content-targeted ads in emails newsletter based on publisher unique content identifier in the email content. The Chennai Patent Office lately published the Indian Patent No. 237567 issued to Google, Inc. for method and apparatus for determining content-relevant ads in emails. The patent is issued against the Application No. 1568/CHENP/2006 filed May 05, 2006 claiming priority from the US Provisional Application No. 60/509,164 which matured into US Patent No. 7,203,684. Google has been expanding its patent portfolio in India and already secured the following Indian patents for advertising business method.

236879 Determining and/or using local location information in an ad system

236106 Method and apparatus for facilitating the serving of ads having different characteristics

235451 Improving advertisement approval

230673 A method of using concepts for ad targeting

227221 Serving advertisements using a search of advertiser web information

226617 A method of serving one or more ads to a user device and an apparatus thereof

225041 Method of determining relevant advertisements

224942 An apparatus for delivering advertising

223351 Serving advertisements using information associated with e-mail

222680 A method of serving advertisements based on content

220065 Methods and apparatus for serving relevant advertisement

219140 A method and apparatus for serving content relevant advertisement with client side device support

208446 A computerized advertisement distribution and delivery system

Sanofi discontinued development of insomnia drug Eplivanserin

Following feedback from the United States FDA for additional clinical data, the French drug marker Sanofi-Aventis lately withdrawn both US and EU marketing authorization applications for insomnia drug Eplivanserin (protected by the US Patent No. 5166416). Sanofi, which over the years occupied a major share in the branded insomnia market by its Ambien Franchise, was counting high on Eplivanserin, the drug that was likely to be the first drug in the class of serotonin receptor to reach the market, particularly following Sanofi’s discontinuation of another insomnia drug Volinanserin (protected by European Patent Nos. 0.208.235 and 0.531.410) in early 2009. Other serotonin receptors that are still running under development in different clinical phases are Pruvanserin (disclosed in WO01007435) by Eli Lilly and Pimavanserin (disclosed in WO0166521) by Acadia Pharmaceuticals.

In India, Pruvanserin is protected by Patent No. 222461 issued against the mail-box Application No. IN/PCT/2002/247/KOL and Pimavanserin is protected by Patent No. 213446 issued against the mail-box Application No. IN/PCT/2002/1019/KOL. However, both Eplivanserin and Volinanserin are pre-1995 molecules and likely not protected under Indian patent law.

Fourth generic drugmaker sued for Analeptic Drug Nuvigil

Cephalon Inc. has filed a civil suit for patent infringement against the generic drugmaker Watson Pharmaceuticals Inc. for its analeptic drug Nuvigil, generically known as Armodafinil. The suit filed on Tuesday (January 05, 2009) in the US District Court for the District of Delaware is to prevent Watson from commercializing the generic Vuvigil product prior to the expiration of Orange-Book listed US Patent No. 7,132,570. Approved by the United States FDA in June 2007, Vuvigil total US sales is approximately USD 42 million for the twelve months ending September 30, 2009 according to IMS Health data. Watson is believed to be “First-to-File” applicant for the 100mg and 200mg strengths of a generic Nuvigil and may be entitled to 180 days of market exclusivity for those strengths. Notably, both 100mg and 200mg strengths got the United States FDA approval on March 26, 2009 almost 21 months later than 50mg, 150mg and 250mg strengths.

Nuvigil’s active ingredient, Armodafinil, is (-)-(R) enantiomer of the racemic drug modafinil also marketed by Cephalon under the brand name Provigil. Provigil is likely to face generics from 2012 and it is considered that Cephalon is looking to protect its sales by switching patients to Nuvigil. Already the generic competition for Nuvigil is getting intense. Earlier in December 2009, Cephalon filed similar suits in the US District for the District of Delaware against three generic manufactures, namely, Teva Pharmaceuticals Inc., Mylan, Inc. and Actavis Inc. for infringement of OB listed US Patent Nos. 7,132,570 (the ‘570 patent), 7,297,346 (the ‘346 patent) and RE37,516 (the ‘516 patent).

Is Section 3 (d) Jeopardizing Innovation?

Section 3(d) is a great piece of legal provision, carefully drafted to negate patent protection for trivial and obvious improvements, in general, made to already known pharmaceutical/chemical substances. Notably, wording of section 3(d) is not open-ended but clearly conditional which leaves room for patent protection for incremental innovations. In fact, any patent application that is rejected u/s section 3(d) must strictly fall within the condition laid down by the section 3(d). However, the application of the section 3(d) by the Indian Patent Office, and more particularly by the Indian Judiciary raised serious questions about the understanding and spirit of section 3(d). In this post, I will try to raise certain points that often puzzled me about the way section 3(d) is interpreted and applied by the Indian Patent Office and Indian Judiciary. I will sincerely welcome and appreciate comments by the readers which help to clarify and add value to the points made in the post.

In Novartis infamous Glivec case, the Madras High Court opined that the efficacy under section 3(d) need to be construed as “therapeutic” efficacy only. Strictly adhering to the Madras High Court opinion, improved efficacy does not include any enhancement in pharmacological parameters (such as bioavailability, toxicity, increased self-life, stability and so on). This mean any physical or chemical improvement made to a known drug substance cannot qualify for patent protection unless and until they do not result into enhanced therapeutic efficacy. Let us consider the Imatinib case. Novartis applied patent application for beta-crystalline form of Imatinib Mesylate which was denied by the IPO and later by the Madras High Court suggesting that improved bioavailability do not account to enhanced therapeutic efficacy.

Suppose if Novartis wanted to have a patent protection for beta-crystalline form of Imatinib Mesylate then what data they need to provide to the IPO in light of the Madras High Court decision? Simple! Novartis need to provide clinical data to prove that beta-crystalline form of Imatinib Mesylate is therapeutically enhanced in treating chronic myelogenous leukemia (CML) when compared to known Imatinib Mesylate substance. In other words, Novartis need to prove that beta-crystalline form is better than known substance not in terms of bioavailability or any other pharmacological parameters but in terms of therapeutic treatment activity (may be something like improving inhibition activity towards tyrosine kinase enzymes). Now the first point that come to my mind is that whether a polymorph or a salt of a known drug substance can improve therapeutic treatment activity, that is, mechanism of drug action of the known drug substance or they are used for improving pharmacological parameters of the know drug substances? I may be wrong in my understanding on this issue but surely would love to hear comments from readers and the industry experts. Whether the Madras High Court opinion of restricting efficacy only to therapeutic efficacy jeopardizes innovation?

Back to Blogging

After a hectic work schedule and a gap of more than two months we are back to our regular blogging. We sincerely apologize to our readers that we abruptly stopped postings without intimidating about our temporary break. However, it is always great to be back in action. We lastly left our discussion on section 3(d) incomplete which we will surely be completing in our coming posts. We will also try to cover and analyze some of recent happenings in Indian patent scenario in particularly Tenofovir patent application rejection, update on Tarceva patent dispute and Bayer Sorafenib patent decision. So let enjoy blogging again and look forward to great discussions ahead.

Is Section 3(d) Separating Wheat from the Chaff?

Prior to the third amendment, the Indian patent law categorically barred patent protection not only to chemical and drug compounds and intermediates but also to pharmaceutical compositions, drug combinations, drug deliveries and any physical/chemical modification to chemical/drug compounds (such as polymorph, co-crystals, complexes, enantiomers and so on). However, ten-year transitional period provided by TRIPS agreement mandated India to allow patent protection to all fields of technology that included drug and chemical products. This mandate was met with strong resistance and protest from local pharmaceutical companies and public health NGOs, and one of the most heated issues was ever-greening. Acknowledging industry concerns about ever-greening and weighing flexibilities provided under TRIPS agreement, the Government of India diligently amended section 3(d) to separate wheat from the chaff. In other words, section 3(d) was amended to separate genuine inventions from frivolous inventions. In patent law, a frivolous invention is an invention which fails any of three criteria of patentability, that is, novelty, inventive step and utility. But if an invention satisfies all three criteria of patentability then it is not frivolous and is patentable until and unless categorically excluded under the law (such as section 4). Notably, the criteria of patentability are same in almost every country having patent law but the benchmark to judge those criteria may differ country to country (such as judicially evolved doctrine).

What differentiate patent law from other disciplines of law is that this is the only subject of law that specifically and particularly deals with advance science and latest technology. Obviously with the advancement of scientific research and technology, certain practices that may have well thought-out inventive almost a decade back has now become more or less a customary practice to a person skilled in the art. For example, almost 10-15 years back resolution of racemic mixture into isomers/enantiomers was novel and inventive practice considering the state of technology and scientific practice prevailing at that particular point of time but now it has become known and customary to an ordinary person skilled in the art. Similarly, concepts such as bilayer tablet or controlled release formulation using HPMC that may obviously thought inventive almost a decade (or two) back is now a common formulation practice. However, despite such practices becoming customary and obvious in state-of-the-art, patents are regularly been issued for inventions using /based on such practices. Unfortunately, the patent law is not able to keep in race with the changing technology and scientific practices and in many cases still scrutinizing inventions keeping in account decade old scientific practice. Such patents are now a major point of concern in healthcare industry, which not only hamper healthy competition but also create litigious market, and is often used as a part of business strategy positively referred as Product LifeCycle Management and negatively referred as Ever-greening.

History is witness that many countries in past, from time to time, amended their patent law to support their social and economic development and India is no exception to that. In 1970, following observations and recommendations made by Ayyenger Committee, the Government of India abolished patent protection to chemical, drug and food products which was a well-thought recommendation to support social and economic situation of India. The impact of that recommendation resulted into strong indigenous generic drug industry which not only supported widely-concern public health issue but also brought new business and employment opportunities for India. In 2005, India again carefully brought changes to its patent law not only in conformity to TRIPS agreement but also to support its socio-economic development. Inclusion of amended section 3 (d) is an example of such diligent approach to balance social and economic development and at the same time keeping patent law in pace with changing technology and scientific practices.

In our continuing post, we will particularly discuss section 3(d) in detail and will also try to rationalize the spirit and scope of section 3(d). However, we will be happy to welcome comments from our readers on this post and their opinion on section 3(d). Hope we can bring some value and clarity to section 3(d).

IPO Procedures Streamlined - Recommendations of FICCI-DIPP Working Group Accepted

This is further to my blog post on “Patent Prosecution Made Easy” which reflects the initiatives taken by DIPP in making the patent prosecution easier for the applicants upon recommendations given by FICCI’s IPR Division. We would like to inform our readers that a lot more has been achieved as a result of FICCI-DIPP Consultative Working Group on Patents, Designs and Trade Marks System in India (read here).

The IPO has issued a detailed Patent Office Procedures (POP) in an attempt to streamline the procedures of the Patent Office and the POP became effective on July 1^st, 2009. Under the POP, all the functions of the Patent Office, except the administrative functions, are divided under different sections, fixing responsibilities on each individual functionary. There will be separate sections for initial receipt and screening of the patent applications, record management and information dissemination, general patent matters, examination and grant, and patent office journal.

The POP provides for quick digitization of the patent applications, including the amendments filed, in Optical Character Recognition (OCR) format and making it available online for public access. This is a welcome step as this will ease the prior art search of the filed documents which was otherwise not possible with the scanned digitized documents. Also, there are directions in the POP that ensures data verification at various levels before the application is made available to the public, so that the public is able to access the correct information. Now, by the implementation of the POP, the applicants and the patent agents will be able to easily identify the status of their applications and can easily track the movement of the applications. The applicant will easily come to know before which examiner the file is pending, for how long it is pending, etc.

Another major highlight of the POP is that now the information regarding the ‘Working of Patent’, i.e., the extent to which the patented invention has been worked in India, will be made available to the public through the official journal every year. This will prove to be valuable information both for people who are interested in filing the application for grant of compulsory license and for the Government in case the patented invention has not been worked in India. FICCI-DIPP Consultative Working Group advocated for streamlining the Patent Office procedures in various meetings. Any of our readers having any suggestions, recommendations or concerns related to patents, TMs, copyrights and designs, please send it to Sheetal Chopra, Head IPR Division of FICCI at sheetal.chopra@ficci.com so that she make take those issues during various Working Group meetings.

Incremental Patents: IPAB Creates Confusion III

As far as section 3(d) issue was concerned, it was ruled against Novartis. The Appellate Board concluded that the bioavailability is not as same as therapeutic efficacy and hence cannot be considered to prove significant efficacy under section 3(d). What is worth noting is that during discussion over section 3(d), Novartis Counsel argued to the Appellate Board that since it was already acknowledged during the hearing that patent application for beta-crystalline variant of imatinib mesylate is novel and constitute inventive step, so section 3(d) should not be applicable. In reply, the Appellate Board reasoned that since the application for beta-crystalline imatinib mesylate falls under drugs/pharmaceuticals/pharmacology, hence section is applicable.

To sum up the whole IPAB proceedings: the patent application for beta-crystalline variant of imatinib mesylate is found novel and non-obvious (inventive step) but still not allowable under section 3(d). Does this judgment really make sense? In other words, a patentable invention which is novel, non-obvious and industrially applicable will not be allowable under section 3(d). Is this the purpose behind section 3(d) to stop patentable inventions? Or was it included to stop frivolous inventions? The Appellate Board has not only made very irrational reasoning for applying section 3(d) for patentable inventions but also diluted the spirit of patent law. However, the Appellate Board reasoning does not end here they moved a step further to reject application for beta-crystalline imatinib mesylate under section 3(b) on the grounds of public morality (considering pricing issue). The Appellate Board specifically reasoned that Glivec price is too unaffordable to the poor cancer patients in India and hence not allowable under section 3(b). However, we will running a quick post analyzing section 3(d) exclusively and will try to bring clarity and spirit behind the inclusion of section 3(d).

Incremental Patents: IPAB Creates Confusion II

Continuing from our last post where we briefly discussed about the background of rejection of patent application for beta-crystalline variant of imatinib mesylate, Novartis writ petition to challenge the Chennai Patent Office decision and finally the Appellate Board denying the patent application for beta-crystalline variant. Now we will discuss and analyze the findings of the Appellate Board. The main issues raised and discussed were – (1) priority date, (2) novelty/anticipation, (3) inventive step/non-obviousness, (4) selection patent, and (5) section 3(d).

Issue regarding the priority date was decided in the favor of Novartis citing judgment made by Calcutta High Court in Agouron Pharmaceuticals Inc. v. Controller of Patents (AID No. 2 of 2001). The Appellate Board specifically reasoned that issue of priority date for mail-box application need to be considered as per situation on the date of examination not from the date of filing of application.

Novelty/anticipation issue was also decided in favor of Novartis. The Appellate Board specifically reasoned that none of prior art references produced by the Opposing parties disclose or anticipated beta crystalline variant of imatinib mesylate. Discussing anticipation, the Appellate Board also acknowledged the doctrine of enablement and concluded that a person skilled in the art just cannot predict the polymorphism and prepare beta-crystalline imatinib mesylate from EP 0564409 (disclosing imatinib free base and salts thereof) disclosure.

Inventive-step/non-obviousness issue too was decided in favor of Novartis. The Appellate Board specifically reasoned that the Opposing parties has not submitted any evidence that any person has prepared imatinib mesylate and found it to be present only in beta-crystal form prior to the application for beta-crystalline imatinib mesylate. Apart from this, the Appellate Board combined the selection patent argument made by Novartis counsel to strengthen inventive-step of the beta-crystalline form.

Selection patent issue as we already mentioned in our last post, helped Novartis to constitute inventive step for its beta-crystalline imatinib mesylate. The Appellate Board reasoned following minimum guidelines for a patent to be a selection patent.

(1) Whether there is any statement in the specification where the nature of the invention concerns with some kind of selection.

(2) Whether the selection is from a class of substances which is already generally known.

(3) Whether the selected substance in new.

(4) Whether the selection is a result of any research by human intervention and ingenuity opposed to mere verifications.

(5) Whether the selection is unexpected or unpredictable.

(6) Whether the selected substance possesses any unexpected and advantageous property.

The Appellate Board found that patent application for beta-crystalline variant of imatinib mesylate satisfied all the minimum requirements of above guidelines (though we leave it for our readers to decide the merit of the Appellate Board reasoning to reach such satisfaction).

Incremental Patents: IPAB Creates Confusion - Part I

The Intellectual Property Appellate Board (IPAB), so called specialized and apex body for patent and trademark disputes, has finally put the last nail in the three year old, high-profile dispute concerning the patentability of Novartis’s anticancer drug Glivec, specifically beta-crystalline variant of Imatinib Mesylate which earlier got rejected by the Indian Patent Office. Well we personally believe this was one of the important cases that possibly will be deciding factor for incremental patents in India. Though the Appellate Board took a lengthy period of three years to decide the matter but the decision made by the Appellate Board is nothing more than confusion and despair for the Indian Patent Law.

The application for beta-crystalline Imatinib Mesylate (1062/MAS/1998) was filed by Novartis on July 17, 1998 claiming priority from corresponding Swiss application. Importantly, when Novartis filed the application in India, Switzerland was not recognized as a conventional country to India. Technically, a priority can only be claimed to a foreign patent application filing date if the country in which the patent application is first filed is conventional country to the later filed country (concept originated from Paris Convention). In fact, claiming priority from Switzerland was one of the grounds made during the pre-grant opposition. The beta-crystalline Imatinib Meyslate application was filed in 1998 but it was not taken for examination till 2005 (mail-box application). Post 2005, the application was separately opposed by Cancer Patients Aid Association, Natco Pharma Ltd., Cipla Ltd., Ranbaxy Ltd. and Hetero Drugs Ltd. and subsequently got rejected by the Chennai Patent Office on January 25, 2006. Following refusal from the Chennai Patent Office, Novartis filed writ petitions before the Madras High Court against the Assistant Controller decision to reject patent application for beta-crystalline imatinib mesylate. However, during the pendency of the writ petitions, the Central Government by notification made the IPAB operational and following that the Madras High Court transferred the writ petitions to the Appellate Board to decide the patentability of the beta-crystalline variant of Imatinib Mesylate.

On June 26, 2009, the Appellate Board finally denied to allow beta-crystalline imatinib mesylate application for grant of a patent. In its 192-pages decision (a copy of judgment can be found on the website of SpicyIP and we sincerely appreciate Shamnad for the same), the Appellate Board detailed the lengthy arguments and counter arguments made by the parties during the hearing focusing on issues of priority date, anticipation, inventive step, selection invention and section 3(d). Odd 133 pages discussed the arguments made by the parties, however, one of the arguments that we would like to make special mention is argument made by Novartis Counsel in support of patentability of beta-crystalline imatinib mesylate. Novartis counsel interestingly brought concept of selection invention in context of polymorph which was quite unlikely. This argument was strongly opposed by the defendants. The concept of selection invention is often discussed when a particularly compound/group of compounds is claimed from earlier known markush structure, even selection of specific salt of drug compound is considered to be selection invention. During the hearing, Novartis Counsel puzzled the Appellate Board by combining two different phenomenons to make case of selection patent, first selection of mesylate salt from large number of known salts of imatinib and second selection of beta-crystal. Interestingly, Novartis Counsel was successful in making the Appellate Board accept the argument for selection invention in context of polymorph application and also to consider that such selection constitute inventive step.

Patent Prosecution Made Easy

One of our great friend and well wisher, Sheetal Chopra has updated us that the Indian Patent Office has decided to issue electronic notifications to patent applicants. This step is a landmark achievement in the history of the Patent Office and was a long felt need to the patent stakeholders. FICCI, during the fifth Consultative Working Group Meeting on Patents, Designs and Trademarks in India held in April 2009, made strong recommendations to the Patent Office about the need for initiating electronic correspondences regarding any matter related to patent prosecution. The notification has become effective on the 1st of July, 2009. This has come as a great respite for applicants or patent agents as they would now be receiving all communications from the Patent Office, including notices and examination reports, electronically. Further, the notification also directs the applicants and patent agents to provide their email ids at the time of filing the patent application.

The new mechanism of sending electronic communication will alleviate the burden of both the Patent Office and the applicants. The significance of electronic communications in the digital era has been reiterated time and again as the easiest mode of communication, with provisions for easy access and storage. Further, the applicants need not be physically present at the mailing address. Another major problem with paper communication was the delay in receiving the communication, which can even result in abandonment of the patent application. This issue also is resolved by resorting to the electronic mode of communication. Introduction of electronic correspondence is a boon for stakeholders as it will ease the task of patent prosecution in India, especially for applicants residing in foreign countries. Mr. P H Kurian, Controller General of the Patent Office, deserves to be appreciated for this major accomplishment and for his zealous efforts to reform the patent regime in India. This is a major step taken by the Patent Office to reaffirm its commitment to raise its standards and competence at par with international standards and also to expedite the patent granting process.

Patent Circle would also like to thanks and appreciate the contribution and painstaking efforts made by Sheetal and FICCI in recommending and bringing constructive changes in the working of the Indian Patent Office. We hope their efforts and hardwork will continue to bring positive changes and transparency in the Indian patent system.

Back from vacation

Sorry we have been out of blogging for quite a sometime now as we took off from our hectic work schedule and went out for vacation at Dharamshala and McLeodGanj both located in Himachal Pradesh in beautiful hills of Dhauladar Range. It was a great trip away from ever running and hectic life of Mumbai. Anyhow it’s time to get back to work and resume blogging. Also, we sincerely thank all our readers who voted for Patent Circle in IPWatchdog voting for top patent blogs. We are pleased to inform that your votes made Patent Circle stood second in the list of favorite blog after Patently-O and fourth in the list of regularly read blog. However, in overall ranking which combines Technorati and Alexa ranking, we slipped to 24th position.

Vote for the Top Patent Law Blogs

IPWatchdog is conducting voting for the top patent law blogs and has listed around 50 blogs to select from. Incidentally Patent Circle is also included in the list. If any of our reader like to vote for Patent Circle (if you think we are deserving enough for your vote) or for his/her favorite patent law blog then visit this link and vote for your favorite blog. 

Indian Patent Office Categorized Examiners and Controllers into Technology Groups

Following earlier circular dated April 29, 2009, the Controller General of Patents P.H. Kurian in its latest circular dated May 13, 2009 has categorized Examiners and Controllers in all four patent offices into Technology Groups. The move is to uniform allotment of patent applications for examination at the Patent Offices as per field of expertise to the controllers/examiners and to further improve quality of patent examination. Each group is having a Group Leader. On the first Monday of every month, the Group Leader is likely to receive required number of files from the Record Section based on the serial order of the Request of Examination pending under the Group Subject. Files will be allotted to the group members after group discussion. Group 1 is for Chemistry and Allied Subjects covering chemistry, biochemistry, pharmaceuticals, agrochemicals and food. Group 2 is for Biotechnology, Microbiology and Allied Subjects. Group 3 is for Electrical, Electronics and Related Subjects covering electrical, electronics, computer, communication and biomedical engineering and physics. Group 4 is for Mechanical Engineering and Other Subjects covering mechanical, civil, textile engineering and other subjects not specified in other groups. As a patent pracititioner, this move is highly appreciable as this will not only able to improve quality of examination but also help patent agents to effectively prosecute patent applications and put across their technical opinions.

More Problems for Tarceva

Revolutionary anticancer drug Tarceva seems to be moving more into problems now. Last month, the Delhi High Court in highly unexpected findings that may create setback for drug research companies in India concluded that if an active ingredient (Erlotinib hydrochloride) of the drug (Tarceva) is sold in a polymorphic Form then that active ingredient in not covered/protected by the compound (drug substance) patent. To cut short, Pfizer received Indian Patent No. 196774 (the ‘774 patent) for Erlotinib hydrochloride (corresponding of US 5,747,498) and had a pending application for polymorphic Form B of Erlotinib hydrochloride (corresponding of US 6,900,221) which eventually got rejected in pre-grant opposition filed by Cipla. Both corresponding US patents are listed with Orange Book as Tarceva marketed tablet formulation contain polymorphic Form B. Roche brought infringement suit against Cipla with respect to granted patent in India (the ‘774 patent) but in counter-claim Cipla argued (rather framed argument) that Tarceva sold in India is polymorphic Form B of Erlotinib hydrochloride and not Erlotinib hydrochloride per se covered by granted the ‘774 patent. The Court unhesitantly agreed with Cipla’s arguments that Tarceva sold in India is not covered by granted ‘774 patent claiming Erlotinib hydrochloride but is a polymorphic Form B for which Roche do not hold a patent. Knowing that the Indian Courts are unfamiliar with even basic understanding of pharmaceutical patents and technical know-how of pharmaceutical science, Cipla opportunistically deceived the divisional bench by arguing that the ‘774 patent covering Erlotinib hydrochloride per se is a mere admixture of polymorph A and B of Erlotinib hydrochloride. Cipla further argued that since the ‘774 patent is admixture of polymorph A and B of Erlotinib hydrochloride and marketed Tarceva tablet is polymorphic Form B, Roche cannot sue them for the ‘774 patent. Further capitalizing on admixture of polymorph A and B story, Cipla also challenged the validity of the ‘774 patent arguing that polymorph are not patentable under section 3(d). Unfortunately, the divisional bench was so inclined by Cipla’s arguments that the Court penalized Roche to pay Cipla Rs. 5 Lakhs (approx. USD 10000) for making false case against Cipla for the drug Tarceva for which Roche did not yet hold a patent. Surprisingly, the divisional bench never even bothered to look into independent claim of the ‘774 patent which reads as –

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

Clearly the independent claim is no where restricted to any polymorph form or admixture polymorph A and B of Erlotinib hydrochloride (as argued by Cipla). The independent claim is covering compound Erlotinib hydrochloride per se and technically such claim cannot be circumvented and designed around by any polymorphic Form of Erlotinib hydrochloride (even a fresher working in pharmaceutical patents reasonably knows that). Why the divisional bench do not refer to the claims of the ‘774 patent? Though after reading the case we feel even the divisional bench would have referred the claims of the ‘774 patent they would not have understood anything (we are least confident about the divisional bench familiarity with basic pharmaceutical science and claim construction). But what is really interesting is the tactic used by Cipla’s lawyers (though completely and technically fallacious) that worked in favor of Cipla. What Roche lawyers can do in a case where unexpected arguments were raised by Cipla’s lawyers (which they possibly never thought in wildest dream) and the divisional bench was not familiar with nuances of basic pharmaceutical science and patent? Just imagining what Roche counsels back in Swiss Headquarters thinking about the judgment?

At least this case gives a cautionary picture that patentees should not be surprised to hear any unexpected reasoning from the judiciary and may think twice before spending money in procuring patents in India that may worth nothing after issuance. At least such decisions will be enough to shatter confidence of small companies and inventors who spent a decent amount of money to file and procure patents in India. How such small companies and inventors will be able to enforce their patents (most of them even do not have enough money to fight litigations). Companies like Cipla will always take advantage of system shortcomings, sometimes playing trump card of public health for their business interests whereas research/innovation will continue to die the way it is dying in India for so many years, decades.

Coming back to Tarceva, lately the United States Food and Drug Administration (FDA) announced a black box warning for Tarceva (read here). In a letter dated April 2009, Genentech and OSI said that there had been reports of patients suffering gastrointestinal perforations while undergoing Tarceva therapy. This risk is greatest for patients receiving concomitant anti-angiogenic agents, corticosteroids, NSAIDs, and/or taxane-based chemotherapy, or who have prior history of peptic ulceration or diverticular disease. According to the letter, some instances of perforation had been fatal. The letter also said that some Tarceva patients had developed bullous, blistering and exfoliative skin conditions, which in some cases were suggestive of Stevens-Johnson syndrome or toxic epidermal necrolysis. Finally, the letter warned that patients treated with Tarceva had experienced corneal perforation or ulceration. Other eye disorders including abnormal eyelash growth, keratoconjunctivitis sicca and keratitis, have also been observed with Tarceva treatment. Last year in October, we reported Tarceva post-approval study reported a death. Such studies and report are often done by Innovator to avoid any post-launch tragedy.

Wyeth-Lupin Settles Effexor ER Patent Dispute

Business Standard reports on patent infringement settlement between Wyeth and Lupin over USD 3 billion antidepressant drug Effexor ER, generically known as Venlafaxine extended release capsule. As per the term of settlement, Lupin will be licensed to launch a generic version of the drug in the US after June 01, 2011, or earlier under certain circumstances (not disclosed) but not before January 01, 2011. Lupin earlier filed a paragraph IV certification challenging the validity or non-infringement to to Orange Book listed US Patent Nos. 6,274,171, 6,403,120 and 6,419,958. This settlement will give Lupin a definite launch date as OB listed patents for Effexor ER will run expiration till late September 2017, however, what would be really interesting is the profit margin that Lupin will possibly be making from this settlement considering that Wyeth had already made multiple settlements for the same drug with other generic drug manufacturers. Lupin settlement agreement is quite similar to Wyeth’s earlier settlement agreements with Impax Labs and Anchen Pharmaceuticals for the same drug. In July 2008 and November 2008, Wyeth under the terms of settlement licensed Impax and Anchen to launch their generic versions of the drug on or after June 01, 2011, or earlier under certain circumstances, but not before January 01, 2011 in return of certain percentage of profits from the generic sale. In October 2005, Wyeth settled patent lawsuit for the same drug with Teva and as per agreement licensed Teva to launch a generic version in July 01, 2010 in return of certain percentage of profits from the generic sale. In October 2007, in a significant development Wyeth issued a “Covenant Not to Sue” Sun Pharmaceuticals for generic tablet formulation of Effexor ER. Sun too filed a paragraph IV certification for the same drug. Wyeth seems to be moving good business strategy by avoiding any further legal cost in patent disputes and at the same time receiving certain percentage of profits from the generic competition.

Chantix Patent in Post Grant Proceeding

Pfizer is involved in a post-grant opposition proceeding for its patent covering hugely popular antismoking drug Chantix. The post-grant opposition is filed by Dr. Reddy’s Laboratories against the Indian Patent No. 204091 (the ‘091 patent) covering tartrate salt of Varenicline, the active ingredient of Chantix. The ‘091 patent is issued against the Application No. 863/MUMNP/2003 and corresponding of Orange Book listed US Patent Nos. 6,890,927 and 7,265,119. Last year in February, Pfizer launched the Varenicline prescription drug in India under the brand name Champix. However, in past there had been an alarming and strong adverse reports related with the use of Varenicline causing a wide spectrum of injuries, including serious accidents and falls, potentially lethal cardiac rhythm disturbances, severe skin reactions, acute myocardial infarction, seizures, diabetes, psychosis, aggression and suicide (read here). In November 2007, the United States FDA issued a safety alert for Varenicline reporting cases of suicidal thoughts and aggressive and erratic behavior in patients taking Chantix. Report also described Chantix affecting patients’ ability to drive or operate machinery. Later in May 2008, the United States FDA issued another alert highlighting important revisions made to the prescribing information for Chantix. Earlier this year in February, CBC News reported that Health Canada received 818 complaints for Canadian patients, many of them reporting mood swings, depression or suicidal thoughts.

We really wonder and concern whether the Indian Drug Regulatory had taken the Varenicline adverse reports seriously enough (read Mint story) and into consideration before giving marketing approval in India. Particularly considering that in India, it is not unusual to buy prescription drugs without doctor’s prescription – Varenicline may seriously pose high risk to Indian patients. And what if Varenicline generic versions also steps in?

Cipla Took the Delhi High Court for a Ride

Finally after quite a hectic work schedule, we got some time to bring analysis on recent judgment by the Delhi HC in a high-profile patent litigation case between Roche and Cipla. On 24^th April, the divisional bench at the Delhi HC dismissed an appeal made by Roche against a last year single judge decision (dated 19^th March 2008) that rejected their appeal for grant of temporary injunction to restrain Cipla from manufacturing, offering for sale, selling and exporting the drug Erlotinib. Almost every leading Indian newspaper covered judgment story, some even provided sort of expert analysis on the judgment. In fact, daily English newspaper Mint quoted “judgment certainly go down as a landmark ruling.” We made this judgment publicly available and downloadable on our blog for our readers on April 27. Hope many of our readers have already gone through the judgment and may also reviewed the decision for its merit both on legal and technical grounds. However, before we proceed with our (as usual) critical analysis on this judgment we would like to know from our readers – how many of our readers think the decision is a landmark judgment? And how many consider the judgment not only lacked to take into account basic technical knowledge but also lacked basic ABC of pharmaceutical patent, reflecting sheer inability of judiciary to handle even not so complex patent issues? Will this judgment possibly go down as a low of Indian patent law? We would surely love to know our readers’ comments on this. This judgment is not a mere judgment but an eye opener to many believing in intellectual property to rethink before investing in research and innovation in India. We do not know what sort of precedent will be set by this judgment but feel that it will considerably question and distort image of Indian patent law. Let us move to our analysis on the judgment. Please note statements included in bracket in bold are our remarks.

After the single judge rejected Roche’s appeal for temporary injunction against Cipla, Roche appealed the single judge decision. However, before deciding the case, the divisional bench reviewed the proceedings and conclusion of the single judge. The divisional bench particularly noted two points in Roche’s plaint made before single judge – (1) Patent No. 196774 (the ‘774 patent) is granted for Erlotinib hydrochloride marketed as Tarceva, and (2) no details of the specification of the ‘774 patent or the x-ray diffraction of Tarceva or Cipla’s generic product (Erlocip) was indicated [wonder why XRD data is asked by the single judge/divisional bench, particularly when Roche filed for infringement of Erlotinib drug compound patent not a particular polymorph patent?]. The divisional bench also noted arguments made by Cipla before single judge against the injunction application which include the following notable points.

(1) questioned the date of grant of patent, and also argued patent could not be presumed to be valid unless it was more than six years old,

(2) argued invalidity of patent under section 3(d) and obvious to a person skilled in the art, particularly argued the alleged patented product (Erlotinib) is nothing but a derivative from Gefitinib,

(3) argued patent is not worked fully and commercially in India, further adding no sales figures for the product for India provided in the plaint.

(4) argued public interest issue that the drug should be made available at cheap and affordable prices.

(5) placed US Pat. No. 6,900,221 (the ‘221 patent) on records filed by OSI for polymorphic Form B of Erlotinib hydrochloride. [this was interestingly deceptive move by Cipla]

The divisional bench also noted counter-claim arguments made by Cipla before single judge, most importantly the argument stating that the ‘221 patent clearly stated that the compound Erlotinib hydrochloride was a mixture of two polymorphs A&B and that one needed to separate and purify that polymorphic Form B so as to get to the claimed compound (Erlotinib) for acceptable efficacy. Further adding that the ‘221 patent clearly defeated the inventive step of alleged invention (the ‘774 patent). [Does this mean that later dated patent is a prior art for earlier dated patent? Quite a new concept framed by Cipla and that too for “compound per se patent”] Cipla further argued [now this is the trick that made real impact on deceiving and confusing both single judge as well as the divisional bench] the ‘774 patent had been obtained by the plaintiffs by suppression of material information stating that the patentee knowingly suppressed the fact that the claimed product is in the form of polymorph.

Cipla further filed an application to dismiss injunction suit before the single judge [this move put the final nail in the coffin]. Cipla argued that plaintiffs filed two separate applications for grant of patent in respect of the same chemical compound for polymorphic Form B. Further arguing the ‘774 patent is mixture of polymorphs A and B which was known to plaintiffs but never stated in the application made before the Patent Controller. Cipla also provided x-ray diffraction data of Tarceva before the single judge to show Tarceva tablets are polymorphic Form B, not mixture of A and B polymorph and based on x-ray data argued that Tarceva sold by Roche in India is covered by pending patent applications and not by granted ‘774 patent. [what a statement made against compound per se patent? Does this mean if an active ingredient of a drug is sold in a polymorphic form then active ingredient is not covered by compound per se patent?] Cipla further argued that case made by plaintiff is completely false and incorrect and also suppressed the fact that it has made two further patent applications for the same compound in polymorphic Form B.

During proceedings, the divisional bench particularly referred to polymorphic Form B story raised by Cipla and was of opinion that the ‘774 patent is for erlotinib hydrochloride polymorph A&B mixture and Tarceva is polymorphic Form B for which the plaintiffs did not yet hold a patent and therefore no prima facie case was made out by the plaintiffs as they were seeking an injunction against Cipla in respect of a drug for which they did not yet hold a patent. [Now this sounds something out of the world analysis that compound per se patent is circumvented by polymorph patent] The divisional bench also was of opinion that the story framed by Cipla had been suppressed by the plaintiffs both before the Controller of Patents as well as in the suit and on this sole ground injunction ought to have been refused. [Now what to expect further when the divisional bench already got preconceived by Cipla’s arguments, better Roche to forget thinking about fair judgment]

The divisional bench further was of opinion that the plaintiff were trying to mislead both the Court as well as Controller of Patents to the effect that polymorph B was subsumed in Polymorphs A and B after the divisional bench found patentee (plaintiff) argument made before the Controller of Patents that the closest prior art i.e. US ‘498 did not teach a compound of polymorph B free of polymorph A contradictory to later statement dated 18^th August 2008 by plaintiff that the earlier compound (disclosed in the ‘498 patent) included all known and unknown polymorphs. [A statement technically and patently correct and widely known to any patent practitioner in pharmaceutical area] But the divisional court opined that if Tarceva correspond to polymorphs A and B then there was no need for the plaintiffs to have applied for a separate patent in respect of polymorph B. [Obviously the divisional bench seems not able to understand basic ABC of pharma patenting]. The divisional bench also pointed that polymorphic Form B of Erlotinib hydrochloride was not known to the plaintiffs at the time they applied for a patent for Erlotinib hydrochloride as a combination of polymorphs A and B and therefore polymorphic Form B could not be said to be subsumed in the compound of combination of polymorphs A and B.

The divisional bench further discusses more issues pertaining to polymorphic Form B, polymorphs A and B mixture which was unfortunately crude, irrational and technically absurd and bizarre to read and understand. We do not even know how to pen down into words, observations made by the divisional bench is not only laughable but also annoying to read. Interestingly the divisional bench was of opinion that an applicant for a patent of a pharmaceutical product be bound to disclose the details of all other applications made by the applicant for grant of patent of derivatives or forms of such product. Also, there are some statements made by the division bench which we have no clue such as this one – “the Controller of Patents has confused the tests of inventiveness with obviousness (page 42).” Interestingly, the divisional bench also was of opinion that the Controller finding about obviousness of Erlotinib hydrochloride during pre-grant opposition is not obviousness but was about anticipation. [Does the divisional bench really understand what anticipation means in patent law?] We would request our readers to please go through the text of judgment, line by line to feel depth of absurdity.

While considering arguments framed by Cipla and observations made by the divisional bench, the Court concluded that Cipla has been able to demonstrate prima facie case that Roche do not hold a patent yet for the drug Tarceva, which is the polymorphic Form B of the substance for which they hold a patent. [Landmark ruling that active ingredient sold in polymorphic form is not covered by drug compound patent!!!] The court also concluded that Roche failure to bring the fact about filing of patent application for polymorphic Form B to the notice of the Controller of Patents was not consistent with the requirement of a full disclosure. Finally the divisional bench fined Roche to pay Rs. 5 lakhs to Cipla. [God knows why?] Is Roche penalized because the story framed by Cipla was suppressed by them?