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Supreme Court stayed the Delhi High Court order of injunction against Glenmark over the Generic drug “Sitagliptin”

Reportedly, Hon’ble Supreme Court of India on Special Leave Petition filed by Glenmark stayed the Delhi High Court order which passed injunction against Glenmark for the generic drug Sitagliptin till 28th April 2015. The Delhi high court on dated 20th March 2015 set aside an order of single judge bench of Delhi High Court which rejected the injunction application by MSD against Glenmark. This article aims to analyze the Delhi High Court judgment by the Division bench in detail. The detailed judgment can be found here.

Facts of the case:

Merck Sharp & Dohme (hereafter “MSD”) aggrieved by the dismissal of its application for an ad interim injunction restraining the respondent/defendant Glenmark Pharmaceuticals (hereafter “Glenmark”) from using its patented product Sitagliptin (Indian Patent No. 209816) filed an appeal. MSD filed an application before single bench Delhi High Court for permanent injunction, restraining infringement of the patent, damages, rendition of accounts and delivery up. The suit patent relates to a drug which lowers blood sugar levels in Type 2 Diabetes Mellitus (“T2DM”) patients. Glenmark opposed the application for ad interim injunction and relied on documents produced during the hearing. The learned Single Judge rejected the injunction application. Aggrieved by the dismissal of interim injunction Merck sought to obtain an interim injunction against Glenmark seeking to restrain Glenmark from selling its Generic products Zita (generic version of Januvia) and Zitamet (generic version of Janumet, combination of sitagliptin+metmorphin).

Argument advanced by the Appellant (MSD): 

The learned Senior Counsel, Mr. T.R. Andhyarujina for MSD argues, that its drug Sitagliptin is the first in its class of compounds that inhibits the enzyme Di Peptidyl Peptidase-IV (“DPP-IV”). The learned counsel argued that the suit patent is infringed because Sitagliptin and any of its acceptable salts are covered by its claims, thus resulting in the making, using or offering for sale, importing into India etc. of Sitagliptin or any of its salts or any form amounting to infringement of the suit patent. It was further argued that Glenmark, by manufacturing, selling, offering for sale and advertising the pharmaceutical combinations Sitagliptin Phosphate Monohydrate under the brand Zita and Sitagliptin Phosphate Monohydrate and Metformin Hydrochloride under the brand name Zitamet infringes the suit patent and all its claims. It was underlined that Sitagliptin Phosphate Monohydrate cannot be prepared without manufacturing the active ingredient Sitagliptin molecule. Therefore, the use of Sitagliptin claimed by IN 209816 to prepare Sitagliptin Phosphate Monohydrate by Glenmark infringes the suit patent. MSD argued that its non-disclosure of applications (which were not pursued by it) was an inessential detail which should not have clouded the debate on whether Glenmark infringed its suit patent. It was submitted that the subject of the European Patent, and the application No. 5948/DELNP/2005 (filed on 18.06.2004 – in respect of the Phosphoric Acid Salt of a DPP-IV inhibitor that claimed Dihydrogenphosphate salt of Sitagliptin and was abandoned under Section 21(1) on 23.08.2010) could not have been the basis for refusing ad interim injunction. In India, on account of Section 3(d) and the interpretation of the expression “efficacy” by courts, MSD abandoned the phosphate salt application.

The learned counsel for MSD argued that Glenmark’s US Process Patent No. US8334385 is for “Process for the preparation of R. Sitagliptin and its pharmaceutical salts”. It was further contended that this patent clearly admits that Sitagliptin is developed for the treatment of T2DM and is the active free base. It also gives the full description of the process for preparing Sitagliptin freebase in the patent specification which is Scheme 6 in Merck’s patent. The claim of Glenmark’s patent is for a crystalline salt of Sitagliptin. The learned counsel relied upon the disclosures made to the suit patent IN 209816 to state that the basic invention for which patent protection was sought was Sitagliptin “with pharmaceutically acceptable salts thereof”. It is submitted that this is clearly stated in claims 1, 15, 17 and 19. Thus learned counsel stressed that Glenmark”s ZITA (Sitagliptin Phosphate Monohydrate) and ZITA-MET (Sitagliptin Phosphate Monohydrate and Metformin) infringe the suit patent because Sitagliptin is made and used by Glenmark in ZITA and ZITA-MET when it makes salt Sitagliptin Phosphate Monohydrate. It was underlined that the phosphoric acid salt of Sitagliptin was disclosed in the suit patent itself as one of the pharmaceutically acceptable salts.

Arguments advanced by the Respondent:

 The counsel for the respondent argued that the suit patent is obvious and does not involve an inventive step over and above previous disclosures in the prior art. It was further argued that the suit patent is anticipated by prior arts European Patent 1406622 and WO/01/34594.

Further it was argued by the Counsel for the respondent that the suit patent drug Sitagliptin as well as Sitagliptin Hydrochloride are unstable compounds possessing incapability of commercial production and industrial use.

The respondent argued that the claim goes much beyond the limited disclosures in the specification, and thus the claim is overbroad or an impermissible Markush claim that creates a false monopoly. It was also contended that the patent monopoly is too broad to be workable as it includes possibly 4.9 billion compounds and such elastic claims cannot be sustained.

It was argued that the complete specification of the suit patent does not sufficiently and fairly describe the invention and the method by which it is to be performed, since the patent does not describe the preparation of the Sitagliptin free base or Sitagliptin phosphate monohydrate, but only its hydrochloride salt.

Further it was argued that MSD did not comply with its obligation under Section 8 of the Act to disclose patent applications made for the “same or substantially the same invention” – it did not disclose 5948/DELNP/2005 (for Sitagliptin Phosphate Monohydrate), 1130/DELNP/2006 (Sitagliptin Phosphate Anhydrate), 2710/DELNP/2008 (Sitagliptin plus Metformin) or subsequent international applications for these compounds either. It was also argued that such suppression and concealment – contrary to statutory obligations – results in the invalidity of the patent, and at any rate, militates against the grant of an interim injunction that is premised on good faith and complete disclosure.

It was argued by the respondent that the suit patent by the plaintiff’s own admission is different from its product. The only exemplified salt being Sitagliptin Hydrochloride, no other salt can be claimed or covered in the impugned salt patent and the plaintiff, by its own admission equivocally, through several documents admitted that the suit patent is distinct and different from the Sitagliptin Phosphate Monohydrate (SPM) as well as its combinations with Metformin Hydrochloride. Urging that the latter two products are the subjects of separate patents, Glenmark highlighted that this is clear admission that they are not covered by the suit patent. In this respect, the details of the plaintiff’s application, i.e. 5148/DELNP/2005, especially, Claim no.1 and International Patent US 2004027983, again claim no.1 are relied upon. The said salt, i.e. SPM was also claimed to possess tremendous advantages over free base and previously disclosed hydrochloride salt. MSD‟s said patent application no. 5948/DELNP/2005 for SPM was specifically abandoned.

Conclusion:

Considering the arguments advanced by both the parties, the court evaluated the three grounds Prima facie case, irreparable injury and balance of convenience for passing interim injunction as below:

1) The court on the first ingredient held that prima facie case had been established by MSD for the fact that Glenmark uses Sitagliptin free base as the active component in its chemical formulation.

2) The court on the issue of whether the claimant would suffer irreparable injury in the absence of interim injunction or not, held in affirmative. The court rejected the argument of Glenmark that injunction should not be granted as the monetary compensation may be granted. On the contrary court opined that prices may not recover after the patentee ultimately prevails, even if it is able to survive the financial setback (or “hit”) during the interim, which may take some time.

3) On the issue of balance of convenience the court held in favor of MSD. On the issue of price difference between the commercial products by MSD and Glenmark is not so startling as to compel the court to infer that allowing Glenmark to sell the drug, at lower prices would result in increased access. However, the court observed that Permitting Glenmark to operate would not necessarily result in lowering of market prices. Hence according to court the balance of convenience lies in favor of MSD.

The court conclusively held that all the three ingredients for passing the order of injunction were established by MSD and hence injuncted Glenmark from manufacturing and selling of Zita and Zitamet.

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

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Generic v. Branded patent battles in India foray into life management diseases too

Patent wars in India between the foreign innovator companies and the Indian generics now seem to be spreading over life-management diseases segment. Till now the patent infringement cases have revolved and are still revolving over drugs for life-threatening diseases such as HIV, cancer where the public interest has played an important factor in the adjudication of the cases. However a recentlaunch of a generic version of Merck’s anti-diabetic blockbuster drug Januvia by Glenmark has opened the gates to India’s its first such patent litigation case in Diabetes market.

Merck sued Glenmark for infringing over it their product patent on Sitagliptin (marketed as Januvia) on April 01st, 2013. Merck sought to obtain an interim injunction against Glenmark seeking to restrain Glenmark from launching its Generic products Zita (generic version of Januvia) and Zita met (generic version of Janumet, combination of sitagliptin+metmorphin). The Delhi High Court however refused to grant the relief to Merck by its decision of April 5th available over here.

The arguments made by Glenmark get the case to follow in a similar direction as Roche v. Cipla. In Roche v. Cipla, Cipla argued that their generic drug Tarceva is a polymorphic form B of Erlotinib Hydrocloride which the valid product patent of Roche does not claim. In addition, Cipla argued that Roche filed a separate Indian patent application on the polymorphic form B which was rejected U/S 3d proving that polymorphic form B is a separate invention not covered in the product patent, on basis of which Cipla was successful in proving non-infringement of the Roche’s patent at the Delhi High Court (the case is now pending at the Supreme Court).One point to be noted is that Cipla sold Tarceva at ~1/3rd of the price of Roche’s marketed drug and that the drug was an anti-cancer agent.

Coming to Merck v. Glenmark, the arguments by Glenmark flowed in the similar direction wherein Glenmark argued that:

  • Merck filed a separate application on Sitagliptin phosphate via 5948/DELNP/2005 which was rejected and affirmatively abandoned by Merck.
  • Merck had also obtained separate US and EP patents on Sitagliptin phosphate wherein Merck admitted that Sitagliptin Phosphate is a new discovery over the main product patent by describing the salt as “novel salt”. Further added that if Sitagliptin phosphate had been not a distinct product from sitagliptin, Merck would not have applied for or obtained a separate patent.
  • Merck suppresses the later Indian patent filing, rejection and abandonment of  5948/DELNP/2005 covering phosphate salt
  • Merck’s ‘816 patent is for Sitagliptin Hydrochloride only and not for Sitagliptin Phosphate
  • Glenmark’s counsel also placed reliance on Novartis Judgement saying “coverage in a patent cannot be permitted to go much beyond the disclosure made by the patentee and that the scope of patent cannot be permitted to be determined by the artful drafting of its claim by skilful lawyers instead of intrinsic worth of the invention”
  • On the basis of the Roche v Cipla judgment, it is further contended that “where the role of variant outweighs the patented claim, there can be no infringement”.

Glenmark, in its arguments, thus relied mainly on separate patent filing on Sitagliptin Phosphate and proving that Merck itself acknowledges that the two are separate inventions and that Glenmark’s selling of the Sitagliptin phosphate salt will not infringe the ‘816 patent.

Merck argued that:

Sitagliptin phosphate being a derivative of Sitagliptin, could not be granted an Indian patent U/S 3d and that the application was misconceived, which was rejected and later abandoned by Merck itself. Merck contended that there are separate patents in US, EP or other countries because there is no section 3d equivalent there. Merck’s counsel also, to allay any influence of the Novartis judgement, contended that there is no price difference in the product of the plaintiffs (Merck) and defendant (Glenmark) and that it cannot be said that the product of the defendant is considerably cheaper than that of the plaintiffs.

According to Judge,

“To my mind, if the infringing product are made with the same object in view which is attained by the patented article, then a minor variation does not mean that there is no infringement. Trifling and unessential variations are to be ignored. Conversely, a miniscule advancement could be recognized as an invention.”

The Judge further added that if it is proved that Sitagliptin phosphate has material effect on the ways Sitagliptin works, defendant would not infringe the plaintiffs patent.

The Judge highlighted that it was for Merck “to have made a case of Sitagliptin Phosphate being merely a new form of sitagliptin which does not result in the enhancement of the efficacy of sitagliptin”, instead Merck only pleaded that Sitagliptin phosphate is same as Sitagliptin which they cannot be prove in light of the separate filing of the phosphate patent.

The Judge therefore did not find Merck to have made case for grant of interim relief and accordingly has dismissed the application. But the court, of course, gave directions to Glenmark to maintain and file accounts of the manufacture and sales of the infringing products every quarter before the Court and to the counsel for the plaintiffs.

Conclusion

It would be interesting to see how this case unfolds during trial, especially it would be interesting to see how strongly the Roche v. Cipla case would act as precedent for this case.  There is a similarity of arguments on separate patent application filing and rejection of new form in both cases. There is a difference however in pricing issues and public interestin this case. In Merck v. Glenmark, Plaintiff’s drug (not an anti-cancer or anti-HIV) was already launched in India with 1/5th of the prices in USA with a current price difference between plaintiff’s and defendent product being ~30% only, unlike in Roche v. Cipla where the plaintiff’s drug was 3 times more expensive than the defendant’s product and was an anti-cancer agent.

Further in Roche v. Cipla, the original product patent did not disclose polymorphic forms A or B even generically. However, in Merck v Glenmark, ‘816 patentnot only discloses pharmaceutically acceptable salts but also mentions phosphoric acid as one of salt forms among a list of other salts. The Examples though disclose only HCl salt forms.

Wouldn’t the test of infringement involve “reading” a claim of the patent onto the potential infringer’s product, wherein if the claim’s elements are found in the product, said product will infringe. In this case, claim 1 in general and claim 19 specifically covers Sitagliptin and pharmaceutical acceptable salts thereof.And thepharmaceutically acceptable salts are defined in the description as:

The term “pharmaceutically acceptable salts” refers to salts prepared from pharmaceutically acceptable non-toxic bases or acids including inorganic or organic bases and inorganic or organic acids……………………….When the compound of the present invention is basic, salts may be prepared from pharmaceutically acceptable non-toxic acids, including inorganic and organic acids. Such acids include acetic, benzenesulfonic, benzoic, camphorsulfonic, citric, ethanesulfonic, fumaric, gluconic, glutamic, hydrobromic, hydrochloric, isethionic, lactic, maleic, malic, mandelic, methanesulfonic, mucic, nitric, pamoic, pantothenic, phosphoric, succinic, sulfuric, tartaric, p-toluenesulfonic acid, and the like. Particularly preferred are citric, hydrobromic, hydrochloric, maleic, phosphoric, sulfuric, fumaric, and tartaric acids  (emphasis added)

Shouldn’t Sitagliptin phosphate gets covered in the ‘816 patent especially due to the fact thatphosphoric acid is mentioned not only in just a laundry list,but is mentioned amongst “Particularly preferred” acids in addition to just 7 other acids?

Furthermore, shouldn’t manufacturing Sitagliptin Phosphate includemaking and using of Sitagliptin,and hence infringe upon ‘816 patent anyways? Shouldn’t Merck prove that manufacturing Sitagliptin Phosphate will infringe its ‘816 patent as the defendant cannot produce Sitagliptin Phosphate without producing Sitagliptin first and thus infringing the ‘816 patent.It might prove to be a better strategy for Merck rather than proving a point that Sitagliptin phosphate and Sitagliptin are same and are claimed in a single patent because filing a separate patent for the salt, arguing in US/EP prosecution that the salt is a novel one and a new discovery over the main patent may go against Merck keeping in view the Roche v. Cipla case, which the court is very likely to follow in this case.

It would be interesting to see how all these factors will be considered by the court in deciding whether Glenmark infringes or not.

About the Author: Ms. Meenakshi Khurana, Patent Attorney at Khurana & Khurana and can be reached at: Meenakshi@khuranaandkhurana.com

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Indian Pharmaceutical Industry Licensing Deals: Case Studies

  • Glenmark Pharmaceuticals

Glenmark, research-driven, global, integrated pharmaceutical company with Research Focus on Inflammatory Diseases, Metabolic Disorders and Pain has a presence in over 80 countries around the world.

The Company has a proven track record of entering into Licensing deals with Big Pharma and entered into Outlicensing deals in 2004 with Forest laboratories for Oglemilast, a drug that was potentially indicated for chronic obstructive pulmonary disorder (COPD) and asthma and was still in the Development Phase at the time of entering into the deal. The potential value of the deal was $ 190 million in US. Glenmark later entered into an agreement with Teijin Pharma Ltd in Japan for the same molecule where the deal value was $53 million. Till date, Glenmark has received $35 million from Forest and $6 million from Teijin.

In a case of In-licensing, Glenmark announced in 2005 a collaborative agreement with Napo Pharmaceuticals for Napo’s proprietary molecule Crofelemer, indicated for four distinct disease categories. Glenmark has Crofelemer rights for diarrhea Indications in 140 Countries. Currently the drug is into the Phase 3 trial and the product launch is expected to happen sometime in mid-2010.

Glenmark entered into an outlicensing agreement with Merck in 2006 for Melogliptin, an anti diabetes target. Glenmark received $ 31 million as upfront payment for the same. But, in an unfortunate development Merck decided to drop off the agreement due to a shift from the focus on anti diabetes segment (2008). Currently, Glenmark is developing the drug on its own and have completed the Phase IIb trials.

In 2007, Glenmark’s in-house developed molecule for a potential treatment of pain was outlicensed to Eli Lilly for an upfront payment of $ 45 million. Only a year after the deal, work on the clinical trial of the molecule was stalled. Both Glenmark & Eli Lilly are currently working on the way forward on the molecule.

Despite suffering setbacks from 2 out of 3 key licensing deals, spirits at Glenmark are high, courtesy the success it is enjoying in the Generics segment. Only last week, Glenmark Generics ltd, was able to ink 3 key agreements that has not only strengthened its position in the global generics market but also established Glenmark as an aggressive player that knows how to make maximum from an opportunity.

Following two patent law suits filed by Glenmark, Medicis Pharmaceutical came to an agreement with Glenmark to let the latter launch the former’s dermatological product Vanos in 2013, long before the patent is set to expire in 2023. In a separate arrangement, Glenmark and Medicis have agreed to jointly develop a product from the former’s pipeline to treat acne. Glenmark is to receive an upfront of $5 million from Medicis. Apart from this, Glenmark had entered into a licensing deal with Sanofi-Aventis for the development and commercialization of novel molecules to treat chronic pain. It has also announced a licensing deal with Par Pharmaceutical to market Ezetimibe tablets.

Very clearly, Glenmark’s business model involve a lot of in-licensing and out-licensing arrangements and the Company wish to ride upon the success of such deals to project itself as an innovation driven global pharmaceutical player. Add to it the rapidly rising of clout of Glenmark in Generics space and its deal-signing spree with pharma majors and it is not difficult to understand on why Glenmark is set to make its mark in the Global Pharmaceutical domain.

  • Dr Reddy’s Laboratories

Dr Reddy’s has been a frontrunner in many aspects of the Indian Pharmaceutical Industry Growth Story that has been witnessed by the globe. Licensing is one of such aspect. In fact, even during the times when India had just opened its gate to a global economy, Dr Reddy’s had inked its first Outlicensing deal.

In 1997, an in-house developed anti-diabetic molecule, DRF 2593 (Balaglitazone), was licensed to Novo Nordisk. In fact, with this deal Reddy’s became the first Indian pharmaceutical company to out-license an original molecule. But, late in 2004, after phase II studies, Novo Nordisk decided to terminate further clinical development of balaglitazone, as the phase II results did not suggest a sufficient competitive advantage for balaglitazone compared to existing products. Post this development, Dr Reddy’s entered into an agreement with Rheoscience for Balaglitazone (DRF 2593). As on January 2010, Blaglitazone (DRF 2593) Phase III clinical trials were announced.

A year later, Dr Reddy’s licensed another anti-diabetic molecule, DRF 2725 (Ragaglitazar), to Novo Nordisk. In 2003, Novo Nordisk, which had suspended trials on Ragaglitazar in 1999 on finding tumors in long-term animal studies, decided to terminate further trials on the molecule completely.

In 2001, Dr Reddy’s Out-licensed DRF 4158, a potential dual-acting insulin sensitizer, to Novartis for an upfront payment of US $55 million. Later in 2003, Novartis decided to discontinue working on DRF 4158, but continued collaborating with Reddy’s for additional development compound that is a dual-acting insulin sensitizer.

Despite a low success rate from its licensing deals, Dr Reddy’s went ahead with one of its molecule and despite criticism from its original licensing partner, Reddy’s now have successfully completed Phase III trials of the same molecule. This clearly depicts the conviction and faith in one’s abilities that Dr Reddy’s has demonstrated for its first in-house developed drug molecule. This in itself stands as a testimony to Dr Reddy’s capabilities to mark new beginnings for Indian Pharma Sector.

About the Author: Mr. Abhishek Sahay is a Senior Patent Consultant at Institute of Intellectual Property Research & Development (IIPRD). Currently, He is working on Patent Licensing Issues in the Life Sciences domain and some of his success stories can be found at http://iiprd.com. He can be reached at abhishek@iiprd.com.