NCEs Outside the Scope of Sec. 3(d), Efficacy Data not Required - II

Continued from our last post where we briefly discussed about the rejection of pre-grant opposition filed by Cipla for the Application Number 3003/CHENP/2004 for anti-cancer drug Nilotinib which later matured into issued Patent Number 237430. The opposition proceedings was fought on the grounds of lack of (1) inventiveness u/s 25(1)(e) and (2) enablement u/s 25(1)(g).

Interestingly during the opposition proceedings Cipla argued against the narrowing of claims which the Controller clearly opined that narrowing of claims are well permissible within the patent law. Cipla also relied on two documents (one of which suggested that polymorphic form B of nilotinib was used for further drug development) published well after the filing date of the Application to contest the utility of the Nilotinib which the Controller rightly rejected from considering to decide the patentability of the Application.

Here again Cipla tried to take the Chennai Patent Office for a ride the way it took the Delhi High Court in infamous Tarceva patent litigation where it convinced the learned Judge that Cipla’s generic Tarceva tablets contain polymorphic form of Erlotinib whereas the patent issued to Roche protects Erlotinib per se and hence non-infringing. Now here Cipla went the opposite way arguing that when the Nilotinib drug development contains polymorphic form B (disclosed in pending Application Number 9925/DELNP/2007 for which pre-grant opposition decision is pending) then patent should not be issued to Nilotinib per se. In other words, if the marketed drug contains polymorphic form of active ingredient then patent should not be granted to active ingredient per se. However, the Chennai Patent Office rightly applied its reasoning rather getting carried away by Cipla’s arguments. 

To be continued…

NCEs Outside the Scope of Sec. 3(d), Efficacy Data not Required - I

Patent Circle earlier posted the issuance of Indian Patent Number 237430 to Novartis against the Application Number 3003/CHENP/2004 for anticancer drug Nilotinib, globally marketed as Tasigna. Like Imatinib and Erlotinib, Nilotinib too belongs to the class of tyrosin kinase inhibitors which is extensively discussed on our blog (read here, here and here). Notably, the Application for Nilotinib before maturing into an issued patent overcame a pre-grant opposition brought by Cipla. The opposition filed at the Chennai Patent Office is one of the well-reasoned and matured decisions (till date) ruled by the Indian Patent Office which is worth discussing here.

The opposition was filed on February 16, 2009 and hearing was held on September 15, 2009. Cipla opposed the Application on the grounds of.

1. Prior publication
   
2. Lack of inventiveness
   
3. Not invention u/s 3(d)
   
4. Lack of enablement
   
5. Failure to disclose information u/s 8
   

However, during the opposition proceedings Cipla dropped most of the grounds and focused on (1) lack of inventiveness u/s 25 (1) (e) and (2) lack of enablement u/s 25 (1) (g). Cipla argued that the use of nilotinib to treat imatinib resistant patients was not disclosed in the specification and was suppressed by or not known to the Applicant at the time of filing the Application. In response, the Applicant argued that the Application is not directed to salts or polymorphs but is directed to New Chemical Entity (NCE) and further argued that the invention is not improving the efficacy of the known compounds but relates to new compounds. Responding to Cipla’s argument, the Asst. Controlled Dr. S.P. Subramaniyan opined that the technical details and use of present invention is clearly described in the specification in accordance with Sec. 10(4) of the Act. He further added that efficacy data is required where substance of any claimed invention falls within the scope of Sec. 3(d) but the present invention is related to New Chemical Entity (NCE) and therefore efficacy data are not required for NCEs.

Patent Circle unquestionably agrees with the reasoning of the Asst. Controller that the NCEs fall outside the scope of Sec. 3(d) and does not require efficacy data to qualify for patent protection within the Indian patent law but the problem lies in Sec. 3(d) itself. In absence of proper guidelines and technical explanation, Sec. 3(d) time and again is used against the NCEs in the shadow of ‘other derivatives of known substance’ used in explanation part of Sec. 3(d). Now can anybody explain that in hardcore synthetic chemistry are there any compounds which are not derivative of known substance (structure)? Even a chemistry graduate can acknowledge the fact that every synthetic compound, whether old or new, are derived from one or the other known substances. In fact, in the drug discovery process the selection of ‘lead’ substance also starts from known substances (not necessarily marketed drug substances). Does that mean identifying a potent drug substance (NCE) from thousands or millions of compounds make NCE a mere derivative and put it in Sec. 3(d) test?

If drug discovery and NCE identification would have been so easy (the way it is portrayed in pre-grant and post-grant oppositions) then one out of every fifth Indian pharma company would have already rolled out their own new drug candidates. Frankly, a country which is still waiting to witness its first indigenous drug candidate to hit the market should not make a patent law that makes drug discovery or NCE identification look like child's play for a person skilled in the art. I wonder does the case of ERLOTINIB and GEFITINIB similar to the case of AMLODIPINE and (Z)-4-[(2-{[4-(2-chlorophenyl)-3-(ethoxycarbonyl)-5-(methoxycarbonyl)-6-methyl-1,4-dihydro-2-pyridinyl]methoxy} ethyl)amino]-4-oxo-2-butenoic acid (AMLODIPINE AMIDE DERIVATIVE) as disclosed in US Patent Number 6,602,893? Are both these cases fall within the scope of derivative? If yes then what is the threshold limit to distinguish NCEs from the derivatives covered in Sec. 3(d)? Obviously one cannot expect the Indian Courts to distinguish NCEs from derivatives especially when they failed to understand even a simple concept that polymorph cannot circumvent compound patent. There is no doubt that the word ‘derivative’ is loosely used in Sec. 3(d) without giving a proper thought about its meaning and scope, which now need explanation about its scope and threshold limit. In fact, the MNCs lately met and asked PMO officials to review and clarify the scope of Sec. 3(d).

To be continued... 

Cipla knocks down key patent blocking i-pill

In another post-grant opposition decided earlier this month, the Mumbai Patent Office revoked Indian Patent Number 202297 issued to Richter Gedon protecting emergency contraceptive pill containing 1.5mg Levonorgestrel, the active ingredient of Cipla’s money spinner i-pill (recently sold to Piramal Healthcare) and Mankind’s Unwanted 72. The ‘297 patent was issued against the Indian Patent Application Number 1119/MUMNP/2003 filed on December 09, 2003. The post-grant opposition was filed by Cipla on February 05, 2008 and hearing was fixed on May 03, 2010. During the hearing, Cipla contested the novelty, prior public use, lack of inventive step, section 3(d), section 3 (e), enablement requirement and failure to disclosed information u/s section 8. The Controller found Cipla’s arguments regarding novelty, lack of inventive step, section 3(d) and section persuasive and subsequently ordered revocation of the ‘297 patent. The ‘297 patent is one of the two patents protecting 1.5mg Levonorgestrel, other is IN206098 issued against the Application Number 75/MUMNP/2004.

Novartis loses DULERA patent in India

Earlier this month, the Swiss Multinational Novartis lost DULERA post-grant opposition to Mumbai-based Cipla as the Chennai Patent Office revoked Indian Patent Number 202350 on the ground of obviousness/lack of inventive step. The ‘350 patent protecting FORMOTEROL FUMARATE and MOMETASONE FUROATE inhalation aerosol combination, the active ingredients of lately approved fixed-dose combination asthma drug DULERA (marketed by Merck) was issued against the Indian Patent Application Number IN/PCT/01/1168/CHE filed on August 20, 2001. The post-grant opposition was filed on February 04, 2008 and hearing was made on July 07, 2010. During the hearing, Cipla argued that the ‘350 patent lacked inventive step as the combination of bronchodilators and steroids for the treatment of an inflammatory or obstructive airways disease are well taught in the art and obvious to a person skilled in the art. Interestingly, the similar combination (having different dose quantity than that of DULERA) was approved in India on December 30, 2009.

APJ Abdul Kalam Speaks

One of the finest scientists India ever produced – APJ Abdul Kalam urges Indian scientists to become pioneers in innovation and technology in his recent speech at the Tata Institute of Fundamental Research. He categorically stressed that India’s present growth has been achieved based on patents generated elsewhere sometime ago as well as innovations and technology developed elsewhere. He also emphasized the need for green energy (read here). PatentCircle whole-heartedly welcomes and appreciates Dr. Kalam views, at least there are people in India who do understand the value of innovation and need to move on from copying to research. We are not sure for how long our country will afford to stay in shades of copying when other Asian countries (China, Taiwan and Korea) aggressively continue to foster in innovation and technology and back here in our country, we continue to discuss the same age old issues of religion, reservation, caste, poverty and corruption. In India, we have objections regarding patents in pharmaceuticals and software because of the vested business interests of Indian companies associated with blatant copying of drugs and software but when it comes to patents in green energy, nanotechnology and stem cell development we have no issues because we have no vested business interests (and possibly no expertise and know-how) as of now to copy them. It is quite unfortunate that despite we have so much potential and caliber to fuel innovation and technology development in India but because of our government ill policies and governance we are contributing far below to our par. India has tremendous potential to become IP and innovation capital of the world but thanks to our copying business industry that we are not able to match our own potential even after 60 years of independence.

Novartis Sues Macleods Over Famciclovir Patent

Novartis has lately filed a civil lawsuit against the Mumbai-based generic manufacturer Macleods Pharmaceuticals Limited for infringement of US Patent No. 5,866,581 listed with the Orange Book for Famvir tablets, generically Famciclovir. The lawsuit is filed in the US District Court for the District of Columbia in response of Macleods submission to the FDA an abbreviated new drug application (ANDA) seeking approval to market generic Famciclovir 125mg, 250mg and 500mg tablets before the expiration of the ‘581 patent. With this development, Macleods is another Indian company that joined the league of Paragraph IV challengers from India.

Piramal acquired i-pill from Cipla

Lately Cipla sold its money-spinning contraceptive brand product “i-pill” to Piramal Healthcare for INR. 95 crores. I-pill is an emergency contraceptive pill containing 1.5mg of Levonorgestrel which was launched by Cipla in the Indian market, followed by another Indian pharma company Mankind under the brand name Unwanted 72. In past, the Government of India criticized and banned airing of i-pill advertisements on television due to irresponsible advertising.

In Europe, 1.5mg Levonorgestrel is marketed as Postinor-1 by Hungarian company Gedeon Richter which holds patent protection for 1.5mg dose of Levonorgestrel as claimed by EP-B1-1.448.207. Bayer and HRA Pharma are two other companies marketing 1.5mg Levonorgestrel in the Europe as Levonelle One Step and NorLevo under license from Richter. In the United States, Gedeon Richter developed and manufactured 1.5mg Levonorgestrel tablet in partnership with Teva Pharmaceutical Industries Ltd. and currently marketed by Duramed Pharmaceuticals under the brand name Plan B One-Step. Gedeon currently has two pending US Application Nos. 20050032755 and 20050288264 for 1.5mg Levonorgestrel.

In India, Gedeon Richter holds two Indian Patent Nos. 206098 and 202297 covering 1.5mg dose of Levonorgestrel. Interestingly, Gedeon that aggressively licensed 1.5mg Levonorgestrel in various developed and developing markets including Canada and the US never initiated any legal proceedings against Cipla and Mankind for launching 1.5mg dose of Levonorgestrel in India. May be Gedeon had no faith in Indian patent system particularly after witnessing big pharma giants like Bristol-Myers, Bayer and Roche miserably failing to stop Cipla from launching generic copies of their patented drugs and enforcing their patent rights in India. Already it is slowly becoming well-known fact that Indian patent has no value, not even worth a paper on which it is issued – thanks to Indian judiciary which went on creating one after one biased and flawed precedents with respect to pharma patents.

As far as my understanding of patent law is concerned, a patent right excludes third party including the Government from the act using, manufacturing or selling the patented product without the permission of patentee. However, the Government may still manufacture or use the patented product under the Government-use exemption. Ironically in India, the Government’s own agency is involved in issuing licenses to third party to manufacture and sell the patented drugs that clearly contravenes the spirit of patent right (obviously allowing third party to manufacture and sell patented drugs from commercial use do not fall within the Government-use exemption) but still Indian judiciary is finding hard to understand that such act of granting licenses to manufacture and sell patented drug constitute violation of patent right under section 47 of the Patents Act, 1970.

Ranbaxy settles with Takeda, is Japanese connection coming into picture?

Diachii-owned Ranbaxy has lately entered into a settlement agreement with the Japanese drug manufacturer Takeda Pharmaceuticals to end patent lawsuit for anti-diabetic drug Actos, generically known as Pioglitazone Hydrochloride. Under the terms of the agreement, Ranbaxy received non-exclusive royalty free license to Takeda’s patents covering Actos and will be able to launch the generic version in the US market on August 17, 2012. Interestingly, Ranbaxy seems to be getting business friendly with Japanese pharma companies, earlier it was Astellas for Flomax and now it is Takeda. No wonder if Japanese connection is coming into picture. Coming back to Actos, Takeda also signed similar sort of agreement with Watson to end patent lawsuits for Actos, allowing Watson to launch the generic version on August 17, 2012.

New Sources (1) the pharmaletter (2) the Economic Times

Para IV lawsuit against Mylan and Famy Care for OC pills

Teva has lately filed civil actions against the generic manufacturers Mylan and Mumbai-based Famy Care Limited for infringement of US Pat No. 7,320,969 and 7,615,545 listed with the OB for oral contraceptive (OC) pills Seasonique and LoSeasonique respectively. Both Seasonique and LoSeasonique are combination of Ethinylestradiol (estrogen) and Levonorgestrel differing only in dose amount, designed for 91 days regimen cycle with 84 consecutive combination pill days followed by 7 consecutive Ethinylestradiol pill days. In past, Teva sued Watson and Lupin for both Seasonique and LoSeasonique, with Watson having the First-to-File (FTF) state for Seasonique but not very clear which generic applicant is having FTF status for LoSeasonique. The lawsuits are filed in the US District Court District of New Jersey.

Does Ranbaxy intentionally forfeited 180-day exclusivity for monetary benefit?

Often strategic business moves are played within the closed walls of the Management Boardroom that can even take market analysts with surprise. Lately, Ranbaxy failed to launch its generic version of Flomax which was expected to go on sales in the US market on March 02 with 180-day market exclusivity. Ranbaxy in its statement reasoned regulatory delay in obtaining final approval for its failure to launch generic Flomax.

Flomax is marketed by Boehringer Ingelhiem in the US and its active ingredient, tamsulosin hydrochloride is protected by the US Patent No. 4,703,063 issued to Astellas Pharma Inc. Ranbaxy had “First-to-File” status for generic version of Flomax, with Impax Laboratories in paragraph IV race. Ranbaxy got sued by Boehringer and Astellas for patent infringement but in November 2007 announced out-of-the-court settlement that allowed Ranbaxy to launch its generic Flomax on March 02, 2010 i.e., eight weeks ahead of the expiration date of ‘063 patent. Similarly, Impax got sued for patent infringement and in October 2009 announced out-of-the-court settlement with Boehringer and Astellas interestingly having similar sort of arrangement (as that of Ranbaxy) that allowed Impax to launch its generic Flomax on March 02, 2010.

Now the question is when Astellas/Boehringer already entered into a settlement deal to allow FTF generic company Ranbaxy to launch its generic Flomax on March 02, 2010 knowing that the Ranbaxy also entitled to 180-day market exclusivity then how Astellas/Boehringer made similar sort of agreement with Impax to allow its generic Flomax launch on March 02, 2010? Does Ranbaxy which received tentative approval for its generic Flomax more than two-and-half years back (June 2007) seriously failed to obtain regulatory clearance despite settling patent dispute back in November 2007 with clear idea of launch date? Or does Ranbaxy made some strategic deal to allow Impax to launch its generic version on March 02, 2010? If yes, then with whom --- Astellas/Boehringer or Impax? Interestingly, a news piece by Livemint.com is suggesting that Ranbaxy may likely to receive one-time payment for enabling the launch of generic version in the US market, and also that Ranbaxy itself allowed Boehringer to bring in Impax for launching generic Flomax.

Delhi High Court directs UCB to approach IPAB

Manish Rajan of livemint.com reported that the Delhi High Court on Monday dismissed the petition filed by Global Biopharma major UCB Frachim against the Indian generic major 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. The High Court directed UCB Farchim to file its appeal before the Intellectual Property Appellate Board instead of a High Court. However, still we are not sure which drug and patent application is subject of dispute. Even the Indian Patent Office does not have the Controller decision uploaded on the IPIRS database.

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).

"7,091,187"

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?