Your Comments

Subsequent to our post on Tarceva Patent Litigation Analysis IV, Patent Circle received a very informative email from one of the readers, who also happens to be one of my friends in patent profession. I reproduce the email below, and would surely be interested to hear what other readers have to say about it. Such efforts by readers will surely make a difference and do help in shaping patent practice in India.

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"Is Erlotinib a derivative of Gefitinib?

1. I agree with your 29th Jan posting.

2. Erlotinib is not a derivative of Gefitinib.

3. It is not even analogue so to say.

4. Since chronologically Erlo came before Gefi, hence one may quote Erlo while describing Gefi.

In fact while I write this note, one interesting fact came to my mind.

Can one call Aceclofenac a derivative of diclofenac?

Yes. It can be (& it is) derived from Diclofenac. But it is not an analogue of diclofenac.

Why?

Because, although both are antiinflammatory, their mechanism of action is different.

Hence even structural similarity not necessarily ensures that the structures would be analogous.

Imagine Aceclofenac product patent application comes to Indian patent office.

Just because Aceclofenac is an "ester' derivative of diclofenac, would you reject it pending rigorous proof of 25-30%plus efficacy vs Diclofenac?

No. Section 3(d) wording is extremely loose and legally reckless.

Derivative: Two structures should be related by simple transformations (bio or chemical) say by 2 to 3 steps. Their functional group transformation should be short easily demonstrable or part of the common knowledge in that field. Shortness is the key. Otherwise all aromatic compounds can be termed as "derivatives" of benzene: that is absurd.

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Analogue: Two facets: Structural: Inspite of structural changes, function is same. Functional: Some property verifying agent like a bio-surface/lectin certifies the functional closeness. Analogue should always be seen in the light of external/third party/biosurface/or some property verifying agent."

Patent Circle Exclusive: Tarceva Patent Litigation Analysis IV

Does Derivative include Structural Analogues?

What is a derivative? Does derivative encompass compounds chemically similar to and synthesized from a known compound? Or does derivative also include structural analogues of a known compound? According to Oxford Advanced Learner’s Dictionary, ‘derivative’ is a word or thing that has been developed or produced from another word or thing, whereas ‘analogue’ is a thing that is similar to another thing. Giving plain dictionary meaning, a derivative is a compound chemically similar to and synthesized from a known compound, which mean that Erlotinib is a derivative of Gefitinib stands fallacious. But it would not be incorrect to state that Erlotinib is a structural analogue of Gefitinib.

In pharmaceuticals, often a new drug class is researched into a family of structural analogues sharing same chemical backbone structure, but such analogues are not necessarily derivatives of other analogue(s) in the same class. It would be absurd if word ‘derivative’ used under section 3(d) read to include structural analogues.

Is Erlotinib a selection invention? To be continue…

Patent Circle Exclusive: Tarceva Patent Litigation Analysis III

Is Erlotinib a derivative of Gefitinib?

Although Erlotinib and Gefitinib have same 4-anilinoquinazoline base structure, but significantly differs in substituents attached at quinazoline and anilino rings. In both Erlotinib and Gefitinib, quinazoline ring is unsubstituted at the 2-, 5- and 8-positions and have anilino substituent at the 4-position and a substituent attached at the 6- and 7-positions.

In Gefitinib, 6-position of quinazoline ring is substituted with 3-morpholinopropoxy and 7-position with methoxy group and anilino ring is substituted with Fluorine and Chlorine, whereas in Erlotinib 6- and 7-positions of quinazoline ring are substituted with 2-methoxy-ethoxy group and anilino ring is substituted with ethynyl radical. It is well recognized in chemistry that a derivative is a compound formed from a parent compound by replacement of one atom with another atom or group of atoms, but retaining essential elements of the parent compound, for example, Flumezapine and Olanzapine belonging to same family of thienobenzodiazepines and sharing same thienobenzodiazepine base structure.

Anyone with a reasonable understanding of organic chemistry would be able to judge that Erlotinib structurally is not a derivative of Gefitinib, even though sharing same 4-anilinoquinazoline base structure. Erlotinib differs structurally from Gefitinib, by substitution of an ethynyl radical for fluorine and chlorine atoms in Gefitinib at anilino ring and substitution of 2-methoxy-ethoxy groups for 3-morpholinopropoxy and methoxy group at the 6- and 7-positions. Then do Erlotinib need to show improved efficacy under section 3(d) of the Act over Gefitinib? According to the explanation provided therewith section 3(d), any derivative of known substance to be patentable under the Act need to differ significantly in properties with regard to efficacy. Considering that Erlotinib is structurally not a derivative of Gefitinib, triggering section 3(d) efficacy requirement will absolutely be excessive.

Does derivative include structural analogues? To be continue…

Patent Circle Exclusive: Tarceva Patent Litigation Analysis II

Erlotinib is reported to be a derivative of gefitinib, and this argument likely to heat up in Tarceva patent litigation. Cipla certainly will contest the validity of the ‘203 patent under section 3(d) of the Act and possibly extend to post-grant opposition under clause (f) of section 25(2) of the Act. Considering lack of know-how in dealing such complex validity, Indian Courts surely have a tough task ahead, and need to be diligent and detailed in delivering judgment.

Quinazoline Family

Quinazoline is a compound made of fused six-membered aromatic rings, a benzene ring and a pyrimidine ring. Gefitinib and Erlotinib belongs to a class of 4-anilinoquinazoline derivatives, an anilino (phenylamino) group attached at the 4-position of quinazoline. Over the years, compounds belonging to 4-anilinoquinazoline family are reported to be useful as an analgesic and anti-inflammatory agent and in the treatment of cancer.

Gefitinib is broadly covered within the markush 4-anilinoquinazoline structure of US Patent No. 5,457,105 (genus patent), and particularly covered within the markush 4-anilinoquinazoline structure of US Patent No. 5,770,599 (species patent). Both genus and species patents are issued to Zeneca and currently listed with the Orange Book. Erlotinib is broadly covered within the markush 4-anilinoquinazoline structure of US Patent No. 5,747,498 (the ‘498 patent). The markush 4-anilinoquinazoline structures are represented below –

Above markush structures have similar 4-anilinoquinazoline base structure, which in fact structurally resembling to anti-cancer markush 4-anilinoquinazolines disclosed in European Patent No. 0 520 722 (‘the 722 patent) issued to Imperial Chemical Industries (ICI) and markush 4-anilinoquinazolines disclosed in US Patent No. 4,464,375 (the ‘375 patent) issued to Sankyo having analgesic and anti-inflammatory properties.

According to the literature citation taken from the genus patent, none of the public disclosure (till that date) reported quinazoline derivative to have anti-cancer properties arising from receptor tyrosine kinase inhibitory properties, and most of the know quinazoline derivatives were reported to possess analgesic, anti-inflammatory, bronchodilator, hypotensive or anti-malarial properties, or tested for antiarrythmic properties. The application for genus patent was filed August 02, 1994 having foreign priority from British patent applications with earliest dated January 20, 1992. Doing some extra-research over the prior art literature, the ‘722 patent seems to be the first patent literature to report and mark a major breakthrough and discovery of new class of 4-anilinoquinazolines for cancer treatment. The ‘722 patent claims priority from British patent applications with earliest dated June 28, 1991. This, in fact, technically suggest that both Gefitinib and Erlotinib are chemical variations of markush 4-anilinoquinazolines disclosed in the ‘722 patent.

Following ICI discovery of new class of 4-anilinoquinazoline inhibitors, AstraZeneca invented first 4-anilinoquinazoline anti-cancer drug candidate Gefitinib, marketed as Iressa followed by Pfizer’s Erlotinib and Glaxo’s Lapatinib (marketed as Tykerb).

Is Erlotinib a derivative of Gefitinib? To be continue …

Happy Republic Day

Patent Granted for Hydrate form of Rosiglitazone Maleate

GlaxoSmithKline has received an Indian Patent No. 213203 (the ‘203 patent) for a novel hydrate form of Rosiglitazone Maleate against the mail-box Application No. IN/PCT/2000/00076/MUM filed December 14, 1998 claiming earliest priority from British patent application dated December 16, 1997. The ‘203 patent titled ‘Hydrate of 5-[4-[2-(N-methyl-N-(2-pyridil) amino) ethoxy] benzyl] thiazolidine-2, 4-dione maleic acid salt’ is lately published in the Patent Office Journal Issue No. 04/2008. Abstract of IN/PCT/2000/00076/MUM reads as –

A hydrate of 5-[4-[2-(N-methyl-N-(2-pryidyl) amino) ethoxy] benzyl] thiazolidine-2, 4-dione, maleic acid salt, characterised in that it: (i) contains water in the range of from 0.2 to 1.1% w/w, and (ii) provides an infrared spectrum containing peaks at 764 and 579 cm-1; and/or (iii) provides an X-ray powder diffraction (XRPD) pattern substantially as set out in Figure II; a process for the preparation of such a compound, a pharmaceutical composition containing such a compound and the use of such a compound or composition in medicine.

Rosiglitazone Maleate, globally marketed as Avandia is patented anti-diabetic drug in US and EU valid till October 2015 and September 2014 respectively. Although not sure exactly in what form claims are issued by the Mumbai Patent Office, but certainly would be interested knowing that. For close reference, refer equivalent US Patent Nos. 6,664,278 and 7,045,633.

USPTO Issued Non-Final Rejection against Gilead's Patents

United States Patent & Trademark Office has accepted Public Patent Foundation’s (PUBPAT) argument that US Patent Nos. 5,922,695, 5,935,946, 5,977,089 and 6,043,230 for Tenofovir Disoproxil Fumarate (collectively ‘Gilead’s patents’) were anticipated and made obvious by the prior art references submitted by PUBPAT during the request for an ex parte re-examination, and has issued a non-final rejection against the Gilead’s patents. USPTO also accepted PUBPAT arguments contesting the priority date of Gilead’s patents. Although Gilead’s patents are issued non-final rejection, but such non-final rejections are not uncommon in the re-examination procedure and are far from over. Gilead will certainly file a response to non-final rejection, and if the USPTO still decide to issue a Final rejection and invalidates Gilead’s patents, then Gilead can possibly appeal to the Board of Patent Appeals and Interferences by filing a notice of appeal, and then to the Court of Appeals for the Federal Circuit.

In India, Gilead’s mail-box Application Nos. 2076/DEL/1997, 963/DEL/2002 and 896/DEL/2002 for Tenofovir Disoproxil Fumarate are pending with the Delhi Patent Office, and the decision of non-final rejection by the USPTO will certainly have statutory duty on Gilead to share such information with the Patent Office under section 8 of the Patents Act 1970. Considering that the proceedings for US re-examination are far from over, it would still be immature to comment about the impact of non-final rejection on the examination and grant of patent in India.

Patent Circle Exclusive: Tarceva Patent Litigation Analysis

Indian pharma market has been a major focused area by global analysts and research-based pharmaceutical companies importantly due to cost competitiveness, world-class infrastructure with highest number of US FDA approved plants outside the US, paragraph IV certifications and overseas acquisitions made by Indian generic companies, but what caught primary attention is introduction (or rather re-introduction) of patent protection for pharmaceutical drug products. Even in India, the analysts and generic companies are largely concerned knowing what drug products been granted patents or against what mail-box drug applications pre- and post-grant oppositions are been made. Noticeably, Indian bloggers particularly Delhi-based Shamnad Basheer of SpicyIP, Hyderabad-based Sandeep Rathod of Generic Pharmaceuticals & IP, Chennai-based Feroz Ali of Pharma Patent, and Mumbai-based Vikas Dandekar of Potent Potions are been instrumental in penning down such patent updates from India. Recently, Indian pharma major Cipla launched a generic copy of patented anti-cancer drug Tarceva which eventually lead Roche to file an infringement lawsuit against Cipla in the Delhi High Court. The case is in preliminary stage of hearing, and as the case proceed it would be interesting to watch the approach of Indian judiciary in handling patent infringement matters for complex compound chemistry. Although Indian bloggers will surely keep track of Tarceva patent litigation, but Patent Circle will additionally keep posting exclusive analysis of Tarceva Patent Litigation. This is the first of our analysis.

No Statutory Exemption!

On 13^th July 2005, Erlotinib hydrochloride, an active ingredient of Tarceva got marketing approval in India for tablet dosage form in 25mg, 100mg and 150mg strengths for the treatment of metastatic non-small lung cancer (source: List of drugs approval during 2005, Central Drugs Standard Control Organization). This gives our first critical parameter in Tarceva Patent Litigation Analysis – Date of marketing approval, which may trigger infringement exemption under section 11A of the Patents Act, 1970.

Reading sub-section 7 of section 11A – (7) On and from the date of publication of the application for patent and until the date of grant of a patent in respect of such application, the applicant shall have the like privileges and rights as if a patent for the invention had been granted on the date of publication of the application: Provided that the applicant shall not be entitled to institute any proceedings for infringement until the patent has been granted: Provided further that the rights of a patentee in respect of applications made under sub-section (2) of section 5 before the 1st day of January, 2005 shall accrue from the date of grant of the patent: Provided also that after a patent is granted in respect of applications made under sub-section (2) of section 5, the patent-holder shall only be entitled to receive reasonable royalty from such enterprises which have made significant investment and were producing and marketing the concerned product prior to the 1st day of January, 2005 and which continue to manufacture the product covered by the patent on the date of grant of the patent and no infringement proceedings shall be instituted against such enterprise.

Proviso of section 11A (7) provides a statutory infringement exemption to generic companies and allow patentee to receive reasonable royalty from generic companies only if the patented product was produced and marketed prior to January 01, 2005. In case of Tarceva, Roche received the first marketing approval post 2005 and Cipla launched the generic version in 2008, which mean Cipla cannot trigger section 11A exemption.

Too Long Compulsory License Period!

Compulsory License is our second critical parameter in analysis. According to section 84 of the Act, any person interested may make an application for compulsory license after the expiration of three years from the date of the grant of a patent, but conditionally on any of three grounds, namely –

(a) reasonable requirements of the public with respect to the patented invention have not been satisfied, or

(b) patented invention is not available to the public at a reasonably affordable price, or

(c) the patented invention is not worked in the territory of India.

As section 83 statutorily limit the application for compulsory license for Tarceva only after three years from the date of the grant of a patent, giving Cipla no option for compulsory license. Tarceva was likely granted patent in July 2007, so the application for compulsory license can only be made post July 2010, which seems to be too long for Cipla to launch the generic version.

Considering both compulsory license and section 11A exemption cannot be triggered by Cipla, Roche has definite case for wilful infringement and may claim injunction and damages under section 108 of the Act. Cipla deliberately infringed Indian Patent No. 196774 (the ‘774), which will further barred Cipla from claiming relief under section 111 of the Act for paying damages.

Roche Moved to Delhi High Court

On January 19, 2008, Roche filed an infringement lawsuit in the Delhi High Court seeking an ex-parte interim injunction against Cipla. As Shamnad pointed out, Roche’s application for an ex-parte interim injunction did not even contain the complete specification of the patent and merely filed a copy of the patent certificate. May be Roche do not have the copy of specification as the ‘774 patent is granted to Pfizer/OSI Pharmaceutical (little guess). In counterclaim, Cipla questioned the validity of the ‘774 patent. The case is still in progress and will likely take some more time to have a decision from the High Court.

Post-Grant Opposition!

According to news source, Cipla is likely to move a post-grant opposition against the ‘774 patent, which is our third critical parameter in analysis. The ‘774 patent was published in the Patent Office Journal dated July 13, 2007. Under section 25 (2) of the Act, any person interested may give notice of opposition at anytime after the grant of patent but before the expiry of a period of one year from the date of publication of grant of a patent, which gives Cipla gives a valid period for filing a post-grant opposition with the Indian Patent Office. The ‘774 patent will be open for post-grant opposition till July 13, 2008.

Patent Number: 196774 Patent Application Number: 537/DEL/1996 Date of Application: 13/03/1996 Date of Priority: 30/03/1995 Title of the Invention: A Novel [6,7-bis(2-methoxyethoxy)quinazolin-4-yl]-(3-ethynylphenyl) amine hydrochloride and a process for preparing the same Name of Patentee: Pfizer Products Inc., OSI Pharmaceuticals Date of publication of Abstract u/s 11A: 11/03/2005 Appropriate Office: Delhi

Source: The Patent Office Journal dated July 13, 2007

Cipla may likely contest the validity of the ‘774 patent under clause (e) and (f) of the section 25(2) of the Act, which read as –

(e) that the invention so far as claimed in any claim of the complete specification is obvious and clearly does not involve any inventive step, having regard to the matter published as mentioned in clause (b) or having regard to what was used in India before the priority date of the claim.

(f) that the subject of any claim of the complete specification is not an invention within the meaning of this Act, or is not patentable under this Act.

To be continue…

Finally Roche Filed Patent Infringement Lawsuit Against Cipla

Cipla has finally launched a generic onslaught on anti-cancer patented drug Tarceva and reported to be convinced that Tarceva is not patentable and has strong case to oppose despite patent granted in India. Following the generic launch, Roche has filed an infringement case against Cipla in the Delhi High Court, which came up for its first hearing on Friday. Cipla launched generic Tarceva at Rs. 1600 compared to Roche Rs. 4800 per tablet.

Erlotinib hydrochloride, an active ingredient of Tarceva is granted Indian Patent No. 196774 (the ‘774 patent) by the Delhi Patent Office against the mail-box Application No. 537/DEL/1996 filed March 13, 1996. Under section 25(2) of the Patents Act 1970, the ‘774 patent statutorily can be opposed within one year from the date of grant of patent, which Cipla may likely consider opting for. Interestingly, Hyderabad-based generic company Natco filed a pre-grant opposition against the Tarceva mail-box Application but subsequently rejected by the Delhi Patent Office. According to Dr. Gopakumar Nair, “Erlotinib is a derivative of another known cancer drug gefitinib, a pre-1995 invention of European drug maker AstraZeneca. Since the Delhi Patent Office had denied a patent for this drug, a patent for its derivative will not be strong, and the generic company can get the patent revoked through a post-grant opposition.” Under section 25(2) the ‘774 patent can be opposed on any of the eleven grounds –

1. wrongfully obtained the invention,
2. prior publication,
3. subject-matter claimed in already claimed in patent of earlier priority,
4. publicly known or publicly used in India before the priority date,
5. obvious and does not involve inventive step,
6. not patentable subject-matter under the Act,
7. lack sufficient and clear description of the invention, or method by which it is to be performed,
8. filed not within 12 months from the priority date,
9. failure to disclose information under section 8 of the Act,
10. fail to disclose or wrongly disclose the source and geographical origin of biological material used in the invention, and
11. anticipated having regard to the knowledge, oral or otherwise.

Opposition Notes: Rosuvastatin

There had been some reported news in the past that Ahmedabad-based generic company Torrent Pharmaceuticals has made a pre-grant opposition against AstraZeneca blockbuster anti-cholesterol drug Rosuvastatin, but it is not clear against which Application the pre-grant opposition has been made. Globally marketed as Crestor, Rosuvastatin has three Orange Book listed patents –

1. US RE37,314 (the ‘314 patent) claiming priority from Japanese patent application dated July 01, 1991, which exclude any possibility of equivalent Indian Application. The ‘314 patent broadly covers drug compound Rosuvastatin.
2. US 6,316,460 (the ‘460 patent) claiming priority from British patent application dated January 26, 2000 and has equivalent Indian Application Nos. 1403/MUMNP/2005, IN/PCT/2002/00867/MUM and IN/PCT/2002/00112/MUM. The ‘460 patent covers marketed formulation of Rosuvastatin.
3. US 6,858,618 (the ‘618 patent) claiming priority from British patent application dated November 22, 2000 and has no equivalent Indian Application. The ‘618 patent claims method for treating heterozygous familial hypercholesterolemia, which is likely not patentable in India under section 3(i) of the Patents Act, 1970.

There are few other Applications filed by AstraZeneca for Rosuvastatin, which are pending with the Indian Patent Office (not including combination and process patent applications) –

1. IN/PCT/2002/00922/MUM for crystalline salts of rosuvastatin, claiming priority from British patent application dated February 15, 2000 (equivalent US Patent No. 6,841,554).
2. 1201/DELNP/2004 for method of preventing dementia in a patient by administering rosuvastatin, claiming priority from Swedish patent application dated October 19, 2001 (equivalent US Publication No. 20060229321).
3. 112/MUM/2000 for use of particular oral dosage ranges of rosuvastatin to alter beneficially lipid levels or lipid ratios in a human patient, claiming priority from British patent applications earliest dated June 02, 1999 (equivalent WO Publication No. WO0045819).

In above listed patent applications, the Indian equivalent(s) of the ‘460 patent seems to be critical from the generic perspective to Torrent as it cover the PDR (Physician Desk Reference) formula of rosuvastatin, which likely reasoned to be possible Application opposed by Torrent. It would be appreciable if anyone can shed some light over this pre-grant opposition.

Opposition Notes

Opposition Notes will particularly focused to cover pre- and post-grant oppositions filed with any of the Indian Patent Offices for patent applications related to drug compounds, formulations, compositions, or processes thereof under section 25 of the Patents Act, 1970 along with commentaries, preliminary analysis and latest updates. Please note the Indian Patent Office usually does not disclose any particulars about the oppositions, so information posted herein is result of information available for other secondary sources (such as news, articles, press release and so on) and personal understanding. Please do let me know, if there is any error or correction to be made in any of the posts …

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What triggered Natco to seek compulsory license?

In an unprecedented move, Hyderabad-based generic company Natco has made an application for compulsory license with respect to Indian Patent No. 196774 (the ‘774 patent) issued to Pfizer for anticancer drug Erlotinib Hydrochloride, globally marketed as Tarceva by Genentech (in US) and Roche (outside US). Although this is probably the first instance of compulsory license in India, but what is important to note that Natco is seeking compulsory license to export 30,000 tablets of Tarceva to Nepal, not for domestic market. It is also reported that Natco has offered five percent royalty to Roche. As far as compulsory license provisions are concerned, Natco seems to have triggered section 92A of the Patents Act, 1970 seeking compulsory license to manufacture and export patented Tarceva to Nepal, which if granted by the Indian Patent Office will likely make India officially second country after Canada to grant compulsory license to export generic drug under “Paragraph 6 System” as decided in August 2003 by the WTO General Council to implement paragraph 6 of the Doha Declaration on the TRIPS Agreement and Public Health. In October 2007, Canada notified TRIPS Council that it has issued a compulsory license to Apotex to export generic version of patented triple combination AIDS therapy drug, TriAvir to Rwanda following notification to import made by Rwanda in July 2007. Under section 92A, Natco can possibly trigger compulsory license if Nepal has -

1. issued compulsory license for Tarceva, or
2. officially notified/allowed importation of patented Tarceva from India.

The first condition seems to be unlikely reason what may have triggered Natco to seek compulsory license as Nepal is having a status of least-developed country under the WTO, and still have eight more years to bring provision for granting patents for drug products, which in fact exclude any possibility of Tarceva having patent protection in Nepal at least till 2016, and also excluding the possibility of compulsory license issued by Nepal for Tarceva. The second condition can only be triggered following a notification to import by Nepal to TRIPS council, similar to Rwanda.

According to Decision of the General Council over implementation of paragraph 6 of the Doha Declaration on the TRIPS Agreement and Public Health, the obligations of an exporting Member under Article 31(f) of the TRIPS Agreement shall be waived with respect to the grant of a compulsory license to the extent necessary for the purposes of production of a pharmaceutical product(s) and its export to an eligible importing Member(s) in accordance with the terms set below –

(a) the eligible importing Member(s) has made a notification to the Council for TRIPS, that:

(i) specifics the names and expected quantities of the product(s) needed;

(ii) confirms that the eligible importing Member in question other than a least developed country Member, has established that it has insufficient or no manufacturing capacities in the pharmaceutical sector for the product(s) in question in one of the ways set out in the Annex to this Decision; and

(iii) confirms that, where a pharmaceutical product is patented in its territory, it has granted or intends to grant a compulsory license in accordance with Article 31 of the TRIPS Agreement and the provisions of this Decision;

(b) the compulsory license issued by the exporting Member under this Decision shall contain the following conditions:

(i) only the amount necessary to meet the needs of the eligible importing Member(s) may be manufactured under the licence and the entirety of this production shall be exported to the Member(s) which has notified its needs to the Council for TRIPS;

(ii) products produced under the licence shall be clearly identified as being produced under the system set out in this Decision through specific labelling or marking. Suppliers should distinguish such products through special packaging and/or special colouring/shaping of the products themselves, provided that such distinction is feasible and does not have a significant impact on price; and

(iii) before shipment begins, the licensee shall post on a website the following information:

- the quantities being supplied to each destination as referred to in indent (i) above; and

- the distinguishing features of the product(s) referred to in indent (ii) above

(c) the exporting Member shall notify the Council for TRIPS of the grant of the licence, including the conditions attached to it. The information provided shall include the name and address of the licensee, the product(s) for which the licence has been granted, the quantity(ies) for which it has been granted, the country(ies) to which the product(s) is (are) to be supplied and the duration of the licence. The notification shall also indicate the address of the website referred to in subparagraph (b)(iii) above.

It would be interesting to know how Indian Patent Office is going to take this forward, and under what provision the compulsory license will be granted to Natco (if granted). It would also be interesting to know whether Nepal has made any notification to TRIPS Council for importation of Tarceva from India (or any other country). Till date, the official website of WTO does not show any notification by Nepal for importation of patented Tarceva from India.

IPO Scoreboard

IPO Scoreboard will track number of patents issued by the Indian Patent Office (Delhi, Mumbai, Kolkata and Chennai) from January 2008 onwards, and will also bring some analytical figures and numbers related to key assignees and patents. Although numbers represented here are carefully monitored, but still need to be double checked before making any possible remarks and forecasts. We hope readers’ will find it useful and interesting monitoring IPO scoreboard. So, let’s get started with few quick facts about the Indian Patent Office.

² There are four Patent Offices in India located in Delhi (Northern region), Mumbai (Central region), Kolkata (Eastern region) and Chennai (Southern region).

² Patent Offices along with Trademark Registry are situated in huge state-of-the-art Boudhik Sampada Bhawan.

² Every Friday morning, the Patent (Official) Gazette is published by the Patent Office.

² Recently Indian Patent Office made e-filing of patent and trademark applications operational.

² In Hindi, Patent is referred as Ekaswa and Intellectual Property as Boudhik Sampada.

Tyrosine Kinase Inhibitors: Patent Status in India?

Tyrosine kinase inhibitors are significantly important class of molecular target agents for the treatment of several cancers, and have considerably drawn attention in India mostly during pre/post grant oppositions. Over the last few months, three important tyrosine kinase inhibitors made news columns in India -- namely Imatinib (Gleevec), Gefitinib (Iressa), and Erlotinibe (Tarceva) -- all opposed by Indian generic companies during pre-grant opposition period. Out of these three, Gefitinib eventually lost the bid for Indian patent and is rejected by the Delhi Patent Office on the ground of prior knowledge, and Imatinib although rejected by the Chennai Patent Office but the final decision has to be come from the Intellectual Property Appellate Board. Only Erlotinib managed to escape through the pre-grant opposition and granted patent by the Delhi Patent Office, but after news spreading about the Cipla’s claim to launch generic version the game seems to be not over for Erlotinib. Apart from these already targeted tyrosine kinase inhibitors, there are some important ones pending with Indian Patent Offices including Nilotinib and Sunitinib. Not sure whether any of other below mentioned drugs are been opposed or not, but will be pleased anyone sharing information about any changes in below status.

Generic/Brand Name	Status
Imatinib Mesylate/Gleevec Novartis	Application No. 1602/MAS/98 for beta crystalline form of Imatinib rejected by the Chennai Patent Office. Novartis appeal pending for hearing in the Intellectual Property Appellate Board. Application(s) for pre-grant opposition made against Application No. 799/CHE/2004 for alpha crystalline form of Imatinib at the Chennai Patent Office.
Sunitinib Malate/Sutent Pfizer	Application No. IN/PCT/2002/00785/DEL for Sunitinib molecule is pending with Delhi Patent Office. Till date not heard any opposition made against the application.
Gefitinib/Iressa AstraZeneca	Application No. 841/DEL/1996 for Gefitinib molecule rejected by the Delhi Patent Office following pre-grant opposition by Natco Pharma and JM Pharmaceuticals on the ground of known prior use.
Nilotinib Monohydrate/Tasigna Novartis	Application No. 3003/CHENP/2004 for Nilotinib molecule is pending with Chennai Patent Office. Till date not heard any opposition made against the application.
Lapatinib Ditosylate/Tykerb GlaxoSmithKline	Application No. 1314/CAL/1997 for Lapatinib (genus) molecule is pending with Kolkata Patent Office. Till date not heard any opposition made against the application. Application No. IN/PCT/00/130 for Lapatinib (species) molecule is pending with Indian Patent Office. Till date not heard any opposition made against the application. Application No. IN/PCT/2002/1457 for Ditosylate salt of Lapatinib molecule is pending with Indian Patent Office. Till date not heard any opposition made against the application.
Sorafenib Tosylate/Nexavar Bayer	Application No. 1633/MUMNP/2007 for Sorafenib is pending with Indian Patent Office.Till date not heard any opposition made against the application.
Dasatinib/Sprycel Bristol-Myer Squibb	Application No. IN/PCT/2001/01138/MUM for Dasatinib molecule is pending with the Mumbai Patent Office. Till date not heard any opposition made against the application.

Will Cipla Going to Test or Taste the Changing IP Landscape?

Indian generic major Cipla has made the first wave of ripples in the tranquil IP landscape by informally announcing to launch the generic version of revolutionary anti-cancer patented drug Tarceva in domestic market. According to news sources, Cipla is likely to launch the generic product by next week in India and Roche (an exclusive licensee in India) too is likely to recourse for necessary legal action under the Indian Patent Law. Although largely famous for bringing cheap alternative medicines, Cipla also have the tendency fighting against third party intellectual property rights for critical life-saving drugs and is convinced that Tarceva is not patentable in India. Also, there is a possibility that Cipla may move an application for post-grant opposition at the Delhi Patent Office under section 25 (2) of the Patents Act, 1970.

If launched, this not only going to be a testing time for Cipla but a tough task for the Indian judiciary and Indian Patent Office to decide and deliver a fair and meticulous judgement, what may further decide the course of changing IP landscape in India. Delhi Patent Office has lately granted Pfizer the Indian Patent No. 196774 for Erlotinib Hydrochloride, the active ingredient in Tarceva jointly developed with OSI Pharmaceuticals. In 2000, following merger with Warner-Lambert and in order to meet the US Federal Trade Commission requirements, Pfizer granted all developmental and marketing rights for Erlotinib to OSI for a royalty-free, cashless license. OSI later commenced clinical development and trials for Erlotinib in alliance with Genentech and Roche, and entered into an agreement for the global development and commercialization of Erlotinib. Under the terms of the agreement, Genentech and OSI shared costs and profit-making for commercializing the product in the US and Roche took the responsibility for obtaining regulatory approval and commercialization in territories outside the US and pay OSI royalties on net sales of the product.

“Erlotinib is a derivative of anti-cancer drug Gefitinib” stated Dr. Gopakumar G. Nair, a Mumbai-based patent consultant, further adding that Delhi Patent Office has already denied the patent for Gefitinib and patent granted for its derivative Erlotinib “will not be strong and can be revoked through a post-grant opposition.” Even earlier during pre-grant opposition period the mail-box Application No. 537/DEL/1996 for Erlotinib was opposed by Hyderabad-based Natco Pharma, but was rejected by the Delhi Patent Office. Now only the time will tell, what will be Cipla’s next move? But surely it is going to testing or tasting time!

FICCI launches First Issue of IPR Spotlight

Over the past few years FICCI has been very vibrant in building IP awareness across the Indian industry, and also in bridging constructive dialogs between the Government bodies and various business sectors in strategizing and fuelling effective IP policies. FICCI provides business solutions through research, interactions at the highest political level and global networking.

Last month, FICCI’s IPR division brought its first online publication of bimonthly newsletter -- IPR Spotlight covering "diverse IP topics including patents, trademarks, copyrights, enforcement issues, etc. and FICCI events" with a view to keep the IP community abreast of latest happenings in world of IP. Notably, FICCI had been granted a National Non-Government Organization Observer Status by the Assemblies of the member states of the World Intellectual Property Organization. Patent Circle recommends its viewers to read IPR Spotlight and do send your invaluable suggestions and inputs regarding the same at iprspotlight@ficci.com or to its editors. You can also send a request to iprspotlight@ficci.com for sending all future issues of this newsletter at your E-mail ID or access the same at http://www.ficci.com.

Also, read press release by FICCI recommending the Government to impose exemplary punitive damages on violators of intellectual property rights to restrict the growing incidences of counterfeiting and piracy. Patent Circle would humbly request its global readers, particularly IP attorneys to share their understanding and suggestions in building an effective mechanism for such damages.

Novo Nordisk Patented Chemically Stable Aqueous Insulin

Denmark-based biotech company Novo Nordisk has lately received an Indian Patent No. 209529 (the ‘529 patent) for chemically stable aqueous insulin preparation using comparatively low halogenide (sodium chloride) concentrations (see Official Gazette Journal No. 50/2007 dated December 14, 2007). The patent is issued by the Chennai Patent Office against the mail-box Application No. 1337/MAS/1997 claiming priority from Danish Application No. 685/96 dated June 20, 1996. Interestingly, the ‘529 patent is Indian equivalent of the US Patent No. 5,866,538 which is currently been listed with the US Food and Drug Administration Orange Book for three approved Insulin Injection products -- namely Novolog (insulin aspart recombinant), Levemir (Insulin determir recombinant), and Novolog Mix 70/30 (insulin aspart protamine recombinant). Considering that stability forms a major technical issue in long-term insulin storage, the ‘529 patent seems to give Novo an edge over the generic competitors in ever-expanding domestic insulin market.

Imatinib Loss Will be Novartis Gain

Imatinib Mesylate, a revolutionary first-line therapy for chronic myelogenous leukaemia (CML) has constantly been in news for few years mostly over patent related issues involving Swiss-major Novartis, Indian Generic Companies, NGOs, and Indian Patent System and that also for its beta crystalline form. Although Novartis’s writ challenging the constitutional validity of section 3(d) had already been knocked down by the Chennai High Court, but is keen fighting against the Chennai Patent Office decision rejecting the Application No. 1602/MAS/98 for beta crystalline form of Imatinib Mesylate, which is currently pending for hearing with newly constituted Intellectual Property Appellate Board (IPAB). The Chennai High Court decision, which undoubtedly stayed away from determining the scope of section 3(d) and meaning of ‘efficacy’ came no surprise to Patent Circle, but surely will be looking forward towards IPAB decision.

Imatinib Mesylate Beta Crystalline Mail-box Application

Application Number	1602/MAS/98
Applicant	Novartis AG
Title	Crystal Modification of a N-Phenyl-2- Pyrimidineamine Derivative Processes for its Manufacture and its use
Date of Filing	July 17, 1998
Gazette Date	July 17, 1999
Convention Date	July 18, 1997
Convention	Yes

Source: Ekaswa Database, Patent Facilitating Centre, Department of Science & Technology

Unrelated from Imatinib Mesylate testing time in India, Novartis was busy discovering and conducting clinical trials for yet another breakthrough for chronic myelogenous leukaemia and subsequently obtained the US Food and Drug Administration approval for CML second-line therapy drug Nilotinib Hydrochloride Monohydrate in October last year. Globally launched as Tasigna, Nilotinib belongs to tyrosine kinase inhibitor showing therapeutic indication in patients with chronic myelogenuos leukaemia who are resistant or tolerant to Gleevac (Imatinib Mesylate). According to a press release from the University of Texas MD Anderson Cancer Center, “Nilotinib is up to 50 times more potent than Gleevec because it was designed to more efficiently bind to, and shut down, the protein enzyme responsible for the disease.” According to observation of Hagop Kantarjian, M.D., professor and chair of the Department of Leukaemia, Nilotinib seems to have fewer side effects than Gleevec. Technically, Nilotinib formerly called AMN107 during trials is a derivative of Imatinib and half of the molecule (“the working end”) is the same as Imatinib, but differing in the other half (“the trunk and tail lights”).

Although Imatinib has overall excellent survival rate and showed a remarkable ability to contain chronic myelogenous leukaemia in patients, but still not been able to cure the disease (as reported by Brian Druker, M.D. of the Oregon Health and Science University). The possibility of patients’ developing resistance to Imatinib over course of time and shifting to second-line therapy Nilotinib cannot be ruled out, which may put Nilotinib as a front-runner for the treatment of CML (watch short Nilotinib Animation). Novartis has already received the US Patent No. 7,169,791 (the ‘791) and has pending mail-box application No. 3003/CHENP/2004 with the Chennai Patent Office for Nilotinib, both claiming priorities from British Application Nos. 0215676.8 and 0229893.3. So, irrespective what will be the outcome of Imatinib beta crystalline application in India, Novartis will still gain from the Imatinib (inhibiting) loss!

Nilotinib Mail-box Application

Application Number	3003/CHENP/2004
Applicant	Novartis AG Switzerland
Title	Inhibitors of Tyrosine Kinases
Inventors	Breitenstein Werner Furet Pascal Jacob Sandra Manley Paul William
International Class	C07D
Date of Filing	December 31, 2004
Journal Date	February 17, 2006
Priority Date	July 05, 2002
Priority Country	Great Britain
Priority	Yes

Source: Ekaswa Database, Patent Facilitating Centre, Department of Science & Technology