Indian pharma starts 2010 with infringement lawsuits in the United States

Indian pharma companies started New Year with at least two patent infringement lawsuits filed against them in the United States. First case was filed on 6^th day of the year 2010 by Teva Women’s Health (Duramed) against Pune-based generic manufacturer Lupin Limited (Teva Women’s Health, Inc. v. Lupin Ltd. et al., District Court of New Jersey, Case # 2:2010cv00080). The case was filed in the District Court of New Jersey for infringement of US Pat. No. 7,615,545 lately listed with the Orange Book for newly approved ethinylestradiol and levonorgestrel combination oral contraceptive drug LoSeasonique.

Second case was filed on January 13 by Takeda Pharmaceutical against Hyderabad-based generic manufacturer Aurobindo Pharma Limited (Takeda Pharmaceutical Company Limited et al v. Aurobindo Pharma Limited, New York Southern District Court, Case # 1:2010cv00247). However, we are not sure about the drug product for which patent infringement suit is filed. Readers any information on this.

UCB moves to the Delhi High Court against Cipla & IPO

Press Trust of India (PTI) reported that Global Biopharma major UCB Farchim yesterday approached the Delhi High Court against the Indian generic manufacturer Cipla and the Indian Patent office over rejection of its patent for a new anti-allergic drug. In its petition, UCB requested the court to quash the order passed by the Controller General of Patents on July 24, 2009, rejecting its claims. Admitting the petition, Justice S Murlidhar posted the matter for hearing on January 28, 2010. Indian Patent Office rejected UCB’s claim on the grounds of lack of inventive steps. In the process of rejection, Cipla filed a pre-grant opposition on December 04, 2008. However, news report does not mentioned information about drug name or the patent application number. Even a quick search at the official website of Indian Patent Office does not reveal any Controller’s decision for any UCB patent application. We will appreciate if any of our reader can bring more clarity over the drug and patent number in issue.

Pfizer sues Teva for Zyvox Patent, Eyeing Ratiopharm Acquisition

Pfizer Inc. has filed a civil suit against the generic drug manufacturer Teva Pharmaceutical Industries Ltd. for infringement of US patent for antibiotic drug Zyvox. The lawsuit was filed on January 15 in the US District Court, District of Delaware in response to Teva’s submission of an abbreviated new drug application (ANDA) with the US Food and Drug Administration seeking approval to market a generic version of Zyvox before the expiration of OB listed patents. Zyvox is approved for the treatment of pneumonia and skin infections with global sales of about USD 1.1 billion and US sales of about USD 575 million (Pfizer Inc. et al. v. Teva Parenteral Medicines Inc. et al., US District Court, District of Delaware, Case No. 1:2010cv00037). Notably, both Pfizer and Teva are currently involved in aggressive bidding for acquisition of Germany’s second-leading generic manufacturer Ratiopharm.

Last month, Pfizer Inc. sued Hyderabad-based Dr. Reddy’s Laboratories Ltd. for infringement of US Patent No. 5,969,156 (protecting crystalline form of atorvastatin calcium) for anti-cholesterol drug Lipitor. The lawsuit was filed on December 08 in the same district court following Dr. Reddy’s filing of an abbreviated new drug application (ANDA), seeking approval to market a generic version of Lipitor before the expiration of OB listed patents for Lipitor (Pfizer Inc. et al v. Dr. Reddy's Laboratories Ltd. et al, US District Court, District of Delaware, Case No. 1:2009cv00943).

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Post Grant Oppositions Filed in 2009

Last year, the Indian Patent Office (IPO) reported filing of eight (8) post-grant opposition applications under section 25 (2) of the Patents Act, 1970. The post-grant opposition can be filed against any granted Indian patent within twelve (12) months from the date of publication of grant. List of patents that are opposed under section 25 (2) in 2009 are:

(1) IN214103: Torrent Pharmaceuticals Limited filed opposition on January 30, 2009 against Sankyo/UBE Industries Limited’s Indian Patent No. 214103 protecting pharmaceutical compositions containing Prasugrel and Aspirin for prevention of diseases caused by thrombus or embolus. Prasugrel, marketed as Efient by Eli Lilly is a novel platelet inhibitor approved for use with acetylsalicylic acid (aspirin) for the prevention of atherothrombotic events in patients with acute coronary syndrome (ACS).

(2) IN221171: Cipla Limited filed opposition on February 16, 2009 against Glaxo’s Indian Patent No. 221171 covering Ditosylate salt of anti-cancer drug compound Lapatinib. Lapatinib Ditosylate is active ingredient of Tykerb approved for the combination therapy for breast cancer patients already using capecitabine.

(3) IN220257: Enercon (India) Limited filed opposition on March 05, 2009 against Aloys Wobben’s Indian Patent No. 220257 protecting an inverter for converting a direct current into an alternating current.

(4) IN216080: Cipla Limited filed opposition on March 06^, 2009 against Ivax’s Indian Patent No. 216080 protecting Budesonide and Formoterol combination HFA aerosol formulation.

(5) IN217464: Emcure Pharmaceuticals limited filed opposition on March 27, 2009 against Eli Lilly’s Indian Patent No. 217464 protecting Olanzapine lyophilized product for parenteral administration.

(6) IN221113: Enercon (India) Limited filed opposition on March 30, 2009 against Aloys Wobben’s Indian Patent No. 221113 protecting rotor blade.

(7) IN221017: Cipla Limited filed opposition on April 08, 2009 against Glaxo’s Indian Patent No. 221017 protecting anti-cancer drug molecule Lapatinib. This is the second opposition filed against Glaxo’s Lapatinib product by Cipla.

(8) IN220287: Ranbaxy Laboratories Limited filed opposition on May 21, 2009 against Eli Lilly’s Indian Patent No. 220287 protecting Olanzapine pamoate salts and formulations thereof.

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?