february 2014 January 2014 newsletter · Lyrica to patients through December 30, 2018 in the US,...

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Rabbit antibodies: new cancer treatment options

January 2014

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cASe rePort: SuPreme court reverSeS medtroNic ruling

ASSociAtion focuS: biotecanada

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Gene by Gene and MyRiad settle theiR dispute

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Roche spRinGs a suRpRise in india

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Translating Innovation

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Life Sciences IP Review is published by: Newton Media Limited Kingfisher House, 21-23 Elmfield Road, Bromley, BR11LT, United Kingdom+44 203 301 8200Director Nicholas LipinskiPublisherJohn HaleyTelephone: +44 203 301 8205Email: [email protected] editorMartin EssexTelephone: +44 203 301 8211Email: [email protected] editorLeonie MercedesSub-editorRos BromwichJournalistsEd Conlon, Max WaltersProduction and designFisherman Creative©Newton Media Limited 2014All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electrical, mechanical, photocopying, recording or otherwise without the prior written permission of the publisher.The views expressed in LSIPR are not necessarily those shared by the publisher, Newton Media Limited. Wishing to reflect the true nature of the market, we have included articles from a number of sources, and the views expressed are those of the individual contributors. No responsibility or liability is accepted by Newton Media Limited for any loss to any person, legal or physical, as a result of any statement, fact or figure contained in LSIPR. This publication is not a substitute for advice on a specific transaction. The publication of advertisements does not represent endorsement by the publisher. Life Sciences IP Review (LSIPR): ISSN 2049-2359 (Print)

fighting cancerCancer remains one of the most disturbing words in the English language, so news of a drug that can activate an immune response against tumours is genuinely exciting. California-based Apexigen says its APX005 boosts the body’s immune system to fight cancers that are difficult to treat, such as pancreatic cancer. Other drugs that are on the way from Apexigen will be developed with Chinese companies and so far its partners have filed four investigational new drug applications for products using its proprietary technologies—two of which are currently in phase testing by its partners.As we report in our cover story, this should all mean new options for patients suffering from the cancers that are most worrying for patients and their families.Staying with the subject, Roche has succeeded in securing an interim injunction against Indian biopharmaceutical company Biocon and US-based Mylan, restraining them from referring to its brand names for trastuzumab, a $6 billion-a-year biological blockbuster drug for the treatment of human epidermal growth factor receptor 2-positive (HER2+) breast cancer.While Western pharmaceutical companies have generally struggled to enforce their IP rights in India, the injunction suggests that Roche has shown others the way with an unorthodox but effective stance. We have both the details and two Indian lawyers’ in-depth analysis of this important development.As I take over from Peter Scott in the hot seat here, one thing remains unchanged: we continue to welcome your comments on these stories or on anything else in this newsletter or on our website.Martin Essex, Managing Editor

Contents4 News 4 MyriadandGenebyGenesettleBRCAlitigation 4 AppealscourtrulingblocksLyricacompetition 5 ActavistobuyForestfor$25billion 6 RochesuesMylanoverHerceptinbiosimilar 7 PfizerAustraliafacesantitrustaccusations 8 MSFcriticisesUSpressureonIndianpatentpolicy 8 Novartisboostscancerimmunotherapyresearch 9 BayersettocompleteAlgetaacquisition 10 USChamberofCommerceslamsIndianpatentpractices 10 MerckandSamsungBioepisagreediabetesdeal 12 MyriadtoacquireCrescendo 12 USdistrictcourtinvalidatesMegacepatent

14 IPstrategy:Apexigen Rabbitantibodies:newcancertreatmentoptions

18 Expertcomment SPCs:thesimplestissueisindoubt

20 Casereport Beyondpatentenforcement:theHerceptinPhoenix

22 Expertcomment TheBolarexemption:thequestionofthirdparties

EditorialPanelMaryAnneArmstrong,partner,Birch,Stewart,Kolasch&BirchLLPVictoriaBeniac-Brooks,partner,Marks&ClerkLLPWolfgangBublak,partner,BardehlePagenbergTrevorCook,partner,WilmerCutlerPickeringHaleandDorrLLPGabrielDiBlasi,partner,DiBlasi&AssociatesPaulEngland,TaylorWessingLLPJanisFraser,principal,Fish&RichardsonPCPennyGilbert,partner,PowellGilbertAndrewJenner,directorofIPinnovationandtrade,IFPMAAshwinJulka,managingpartner,Remfry&SagarLarsKellberg,corporatevicepresident,corporatepatents,NovoNordiskA/SJudithKim,partner,Sterne,Kessler,Goldstein&FoxSimonKremer,partner,MewburnEllisLLPNathalieMoll,secretarygeneral,EuropaBioMatthewNielsen,partner,MarshallGerstein&BorunLLPCarolinePallard,partner,NederlandschOctrooibureauMichaelPitzner-Bruun,partner,KromannReumertJoséTrigueros,partner,LeyvaMontenegroTriguerosAbogadosSCJoachimWachenfeld,partner,Vossius&PartnerJaneWainwright,partner,PotterClarksonLLPGordonWright,partner,Elkington&FifeLLP,onbehalfofCIPAFranz-JosefZimmer,patentattorney,Grünecker

NewS4 LSIPR Newsletter 02:14


salt lake city, Us

Myriad and its rival genetic diagnostics company Gene by Gene have agreed to settle their patent infringement case related to BRCA tests.

BRCA tests assess an individual’s risk of developing breast and ovarian cancer by looking for mutations in the genetic sequences of the BRCA1 and BRCA2 genes.

Under the agreement terms, Gene by Gene will stop selling or marketing clinical diagnostic tests in North America that include analysis of the BRCA1 and/or BRCA2 genes. It may continue to sell such tests outside North America.

The parties agreed that Gene by Gene may offer its whole genome and exome—a part of the genome—products and services around the world. These include the BRCA genes and custom array products that test variants for inherited Mendelian disorders—which are caused by mutations in single genes—and may include the BRCA genes.

The agreement will remain in force until February 12, 2016, or when the last of the valid

BRCA patents involved in the case expires—whichever is earlier.

The patent owners have agreed to dismiss the patent infringement case without prejudice.

Myriad filed suit at the US District Court for the District of Utah, Central Division, on July 10, 2013. It accused Gene by Gene

Myriad and Gene by Gene settle bRca litigation

of infringing nine patents covering synthetic DNA and methods of use related to the BRCA1 and BRCA2 genes with its diagnostic tests. The company launched a series of similar cases around the same time last year.

“We believe the settlement with Gene by Gene is a good and responsible agreement,” a spokesperson for Myriad told LSIPR. ➤

Assessing the risks

Overcoming the challenge

appeals court ruling blocks lyrica competitionwashington, Dc, Us

The US Court of Appeals for the Federal Circuit has upheld a patent covering Pfizer’s pain drug Lyrica, closing the market to any generic challengers until 2018.

On February 6 it confirmed a district court’s decision that a group of generic makers, including Teva, Actavis, Sun and Mylan, had infringed a patent covering Lyrica’s active ingredient pregabalin by seeking to market a generic version of the drug.

The court also said that a challenged claim of the patent was valid, despite the generics’ arguments that there is lack of enablement, and insufficient written description or obviousness.

Lyrica is used in the treatment of fibromyalgia, nerve pain and pain after shingles. It is Pfizer’s biggest selling drug, making the company nearly $4.6 billion in revenues in 2013.

Pfizer sued the generic makers at the US District Court for the District of Delaware

the composition of matter patent covering pregabalin, US patent number 6,197,819.

“We hold that the district court did not err in its conclusion that claim 2 of ‘819 has been infringed, and that appellants failed to prove that the claim is not enabled, insufficiently described, or obvious,” Judge Prost wrote in the judgment. She added that the generics’ arguments about the validity of the other disputed patents are moot.

Pfizer’s senior vice president and associate general counsel Michael Parini said: “We are pleased with today’s decision by the Court of Appeals for the Federal Circuit ensuring Pfizer will exclusively provide pregabalin as Lyrica to patients through December 30, 2018 in the US, pending a possible rehearing or appeal of this decision and pending other litigation.”

The generic companies may now request a rehearing by the appeals court or a review by the Supreme Court.

Mylan did not respond to a request for comment. n

in 2009 after they sent Abbreviated New Drug Applications to the US Food and Drug Administration (FDA) seeking approval to market a generic version of Lyrica.

In its complaint, Pfizer initially asserted four patents, although the appeals court found that the case rested entirely on a single claim of

LSIPR Newsletter 02:14 NewS 5


Mallinckrodt to acquire Cadence sharesa subsidiary of Dublin-based Mallinckrodt Pharmaceuticals is to acquire all the outstanding shares of Cadence Pharmaceuticals, the companies have announced.

Cadence is a biopharmaceutical company specialising in commercialising products for use in hospitals. as part of the transaction, Mallinckrodt will add Cadence’s painkiller injection Ofirmev to its portfolio of core controlled substance generics.

“The acquisition of Cadence Pharmaceuticals is consistent with our goal of becoming a leading global specialty pharmaceuticals company,” said Mallinkrodt’s chief executive Mark Trudeau.

“We believe [Ofirmev] will be an outstanding addition to the brands component of Mallinckrodt’s Specialty Pharmaceutical segment.”

The transaction is subject to terms and conditions and is expected to close in mid to late March 2014.

Chicago welcomes new biotech hubMatter, a new hub for healthcare and biotech startups, has opened in Chicago’s Merchandise Mart following a $4 million state investment.

Illinois governor Pat Quinn named the hub as a priority in his State of the State address, and hopes it will drive innovation in medicine and biotechnology in the area.

“We are committed to taking our medical technology industry to the next level,” he said.

“Matter will serve as a central location to empower entrepreneurs and spur economic growth, while advancing Illinois’ role as a national leader in life sciences and health innovation.”

INBRIEF

Taking a slice of the action

DUblin, irelanD

Actavis has announced another expansion with the $25 billion acquisition of US pharmaceutical company Forest Laboratories.

If the acquisition is successfully completed, Actavis said, the companies will make combined annual revenues of more than $15 billion in 2015.

Forest makes blood pressure drug Bystolic and Alzheimer’s disease medicine Namenda. In January, it bought Aptalis Pharma for $2.9 billion, adding a suite of gastrointestinal and cystic fibrosis therapies to its portfolio.

The companies hope to develop franchises in central nervous system, gastroenterology, women’s health, urology and cardiovascular therapeutic areas, and create sustainable portfolios in the infectious disease, respiratory, cystic fibrosis and dermatology categories.

Last May, Dublin-based Actavis announced it would buy Warner Chilcott in a deal worth $5 billion. Paul Bisaro, chief executive

of Actavis, said that the combination of companies creates a “balanced offering of strong brands and generics, and a focus on strategic, lower-risk drug development”.

Forest’s chief executive Brent Saunders said the company was “a great fit” with Actavis, adding that the merger will create a “diversified portfolio and geographically balanced business”.

“The acquisition builds on our blockbuster line call strategy in central nervous system (CNS) and gastrointestinal (GI) drugs and dramatically extends our reach beyond the US market,” he added.

“By joining forces with Actavis, we become more relevant to key physicians and customers through blockbuster franchises in CNS, women’s health, GI and urology, as well as Actavis’ global generics business.”

In November 2013, Actavis and Forest settled a legal dispute related to a patent covering blood pressure drug Bystolic.

The transaction is expected to close in mid-2014 and is subject to regulatory approvals. n

actavis to buy forest for $25 billion

“It is in the best interest of the parties because it ends the uncertainty and expense of ongoing litigation.”

He added that Myriad and the other owners of the BRCA patents at issue, which include the University of Utah, the Hospital for Sick Children, Endorecherche, Inc, and the Trustees of the University of Pennsylvania, continue to believe that these patent claims related to BRCA1 and BRCA2 gene testing are valid and enforceable.

“We are in the early stages of the litigation regarding all the other infringement cases. With regard to Ambry, we are currently waiting for a ruling from Judge Shelby on our motion seeking a preliminary injunction in that case. No trial dates have been set at this time,” the spokesperson continued.

Nabeela Rasheed, a shareholder at McAndrews Held & Malloy Ltd, said that Gene by Gene had taken a “calculated approach”.

“As a business decision it likely makes sense for them to hold off for another two years,” she said.

“The litigation could potentially have taken at least until that time if Myriad were to see the matter up to the appeal process. Given their

past performance it seems quite likely they would have pursued that option.”

She added that Gene by Gene may feel it can afford to settle, saying: “There remain at least five other lawsuits pending. Myriad is going to continue to enforce its patent rights. That has always been its position and I do not think that position will change with this settlement.

“As for Ambry, I believe that company has come out and stated categorically that it will continue with its litigation with Myriad et al,” she continued.

“Ambry seems pretty confident in its position. It remains to be seen how that lawsuit will affect the rest of Myriad’s portfolio. As I have stated in the past, while the Supreme Court decision created significant mischief for the rest of the world prosecuting diagnostic type applications, it had little effect on Myriad because Myriad continued to have method claims and took the position that it would continue its enforcement of the remaining portfolio.”

Gene by Gene did not respond to a request for comment. n



Industry reflects on Strategy for UK Life SciencesThe uK life sciences sector’s four membership bodies have co-published a report about the progress of the uK government’s proposed strategies for making the uK a life sciences leader, which were outlined in a 2011 paper Strategy for UK Life Sciences.

The report described the biomedical Catalyst initiative, which provides grants to support medical research, as a success.

However, the authors said that implementation of the government’s commitments has been inconsistent and in some cases slower than had been hoped, and that progress on actions including the earlier access to Medicines Scheme had stagnated.

It put slow progress down to a lack of resources and leadership within the National Health Service (NHS) at a time of “significant organisational change”, and recommended stronger leadership and accountability between the government and NHS england.

Baker & McKenzie adds to IP teambaker & McKenzie LLP has added to its IP team with the appointment of Hiroshi Sheraton as a partner in its London office.

Sheraton is an experienced patent lawyer, having led and co-ordinated uK High Court cases and pan-european patent litigation.

He specialises in the life sciences industry and has advised clients in the fields of microarray technology, enzymatic research tools, antibody production and medical devices.

Sheraton joins from McDermott Will & emery LLP where he was a partner and co-head of its IP practice. Michael Hart, head of the IP practice at baker & McKenzie’s London office, said Sheraton was an “ideal addition” to the team.

INBRIEFDelhi, inDia

Roche’s Indian subsidiary has sued Mylan and Bangalore-based pharmaceutical company Biocon at the Delhi High Court, for launching a biosimilar of its breast cancer drug Herceptin (trastuzumab).

It has also started a case against India’s Drug Controller General (DCGI) for allowing the launch.

Roche claimed that Mylan and Biocon’s drugs were being misrepresented as “trastuzumab”, “biosimilar trastuzumab” and as a “biosimilar version of Herceptin” without following the “due process in accordance with the Guidelines on Similar Biologics for the purpose of obtaining appropriate approvals.”

It also claimed that there is no public record that shows the firms conducted phase I and II clinical trials for the drug.

Until the next hearing, the court has ordered that Mylan and Biocon do not rely upon or refer to Herceptin, or any data relating to trastuzumab marketed as Herceptin, for selling their own version of the drug.

“It is an extremely shocking, but not unexpected development, especially as Roche had decided not to pursue Indian patents for its breast cancer drug,” Biocon said in a statement.

“This proceeding is an attempt by Roche to protect its market monopoly and prevent Indian patients from accessing a more affordable trastuzumab. Canmab and Hertraz

co-developed by Biocon and Mylan are world-class products that adhere to stringent quality standards and have been developed on the basis of applicable biosimilar guidelines.

“Biocon and Mylan are committed to affordability and access and are driven by their purpose of expanding the pool of patients that can afford trastuzumab. We are confident that once we are heard by the court, this injunction placing certain limits on promotional activities will not stand.”

A spokesperson for Roche told LSIPR: “This legal action is not a patent litigation. Rather, in taking this action we are seeking to clarify whether Biocon and Mylan Inc’s products have demonstrated comparable efficacy and safety to our innovator product trastuzumab, and have been approved as biosimilar products.

“We have taken this action because as the holder of the Herceptin trademark we have a duty to ensure that if a company claims its product is a biosimilar of, or similar to, our innovator product trastuzumab, that this really is the case.”

The spokesperson continued: “As far as we are aware, the Indian regulatory authorities have approved Biocon and Mylan Inc’s products as trastuzumab, as per their regulatory process, but it is unclear whether the products meet the criteria for biosimilar products.”

He added: “Please note that while we have named the DCGI as a party, our actions have not sought to challenge the approvals.” n

For analysis, see page 20

Roche sues Mylan over herceptin biosimilar

Weighing up the evidence

How are we doing?



canberra, aUstralia

Australia’s antitrust regulator has launched proceedings against Pfizer’s Australian arm, accusing it of abusing its power when supplying cholesterol-lowering drug atorvastatin to pharmacies.

The Australian Competition and Consumer Commission (ACCC) said that Pfizer offered “significant discounts” and paid rebates accrued on atorvastatin’s originator product, Lipitor, on the condition that pharmacies acquire a minimum 12-month supply of its generic product.

Pfizer started making these offers when the patent covering Lipitor’s active ingredient expired in 2012. Before the patent expired, Lipitor was prescribed to one million Australians, and made annual sales of AU$700 million ($633 million).

“The ACCC alleges that Pfizer engaged in this conduct for the purpose of deterring or preventing competitors in the market for

atorvastatin from engaging in competitive conduct, as well as for the purpose of substantially lessening competition,” said ACCC chairman Rod Sims.

“Deterring anti-competitive conduct is an ACCC enforcement priority because of the harm that it can cause to the competitive process and ultimately to consumers, particularly with such a widely used product.

“This case also raises an important public interest issue regarding the conduct of a patent holder nearing the expiry of that patent and what constitutes permissible competitive conduct,” he continued.

The ACCC said it is seeking pecuniary penalties, declarations and costs.

A spokesperson for Pfizer told LSIPR: “Pfizer does not ordinarily comment on matters that are before the court. Pfizer believes strongly that the offers referred to by the ACCC were competitive. We will vigorously defend the proceedings.

“As the matter is before the court, it is inappropriate for us to comment further.”

A directions hearing is due to take place on March 18 in the Federal Court of Australia in Sydney. n

pfizer australia faces antitrust accusations

Accused of abuse of power



washington, Dc, Us

Humanitarian organisation Médecins Sans Frontières (MSF) has criticised the US for pressuring the Indian government to review its patent policies.

In a testimony to the US International Trade Commission (ITC) public hearing on trade investment and industrial policies in India, MSF’s director of policy and analysis Rohit Malpani urged the ITC to “evaluate the decisions made by the Indian government under international trade rules, taking in consideration their impact on public health”.

He said that MSF strongly objects to the pressure from the US on developing countries, including India, “for using legal flexibilities to protect public health”.

India’s patent law and judiciary are under pressure for policies that MSF considers “entirely in line with its obligations” as a member of the World Trade Organization, he added.

Describing India as the “pharmacy to the developing world”, Malpani said that India’s role in the treatment scale continues to be “critical”, and that governments “rely heavily” on the country as a source of quality generic medicines.

India is trying to strike a balance between “providing IP protection and having the flexibility to protect the constitutional right to health”, by

defining strict patentability criteria (which he says is in line with international trade rules), and planning to issue compulsory licences.

Treatment providers are already seeing the impact of the thousands of patents that were issued in India between 2005 and 2008, which he said delayed generic competition and kept newer medicines out of affordable reach.

MSF recognises the need to reward innovation, as Malpani said: “R&D is important, and someone needs to pay.

“The reality is that relying on high prices for medicines, backed up by IP monopolies, is a flawed paradigm to pay for medical innovation,” he added.

“We basically have a trade-off between innovation and access.”

At the same hearing, Pharmaceutical Research and Manufacturers of America’s (PhRMA) senior vice president for international affairs Rod Hunter highlighted the industry’s concerns around India’s patent policies.

India’s IP environment does not value innovation, he said. “Despite our member companies’ best efforts to engage in a productive dialogue with the Indian government about the critical link between innovation and patient health, the innovative biopharmaceutical industry continues to face significant barriers in that market,” he added.

Msf criticises us pressure on indian patent policyThe Indian government had created a “protectionist regime that harms US job creators”, he said. “Whereas the US has welcomed Indian companies … India is closing its borders to US innovators,” he added.

“While the Indian government seeks to grow its domestic generic pharmaceutical industry by undermining innovation (local and foreign), US innovative biopharmaceutical companies are merely seeking a level playing field,” Hunter continued.

India’s actions have consequences within India, he said: “It is well established that developing countries gain from high-quality and high-quantity technology transfers associated with foreign direct investment.” But weak IP protection directly discourages such R&D, he added.

He noted that many innovative companies, to ensure their therapies are accessible to patients, have developed patient access programmes. He cited India’s rejection of Novartis’ patent on Glivec (imatinib), even though Novartis provided free access to Glivec for 95 percent of patients in India.

“Our industry, the US economy, and the future of innovation cannot afford to let India continue on this path that discourages new opportunities, new knowledge, and new medicines in India and around the world,” Hunter concluded. n

basel, switzerlanD

Novartis has announced it will acquire biotechnology company CoStim Pharmaceuticals for an undisclosed sum.

CoStim is based in Cambridge, Massachusetts. It focuses on using the immune system to eliminate immune-blocking signals from cancer.

Novartis hopes the CoStim acquisition will accelerate its cancer immunotherapy programme.

It said that there is “increasing evidence” that the immune system has a role in controlling cancer, which suggests opportunities for creating oncology therapies that stimulate a targeted immune response.

Novartis is currently developing chimeric antigen receptor (CAR) technology, a

potential cancer therapy, with the University of Pennsylvania.

Its deal with CoStim adds late discovery immunotherapy programmes that are directed

to targets including PD-1, a protein thought to negatively regulate immune response.

“These medicines could benefit patients by circumventing cancer’s ability to develop resistance against current single drugs,” Novartis said.

Mark Fishman, president of the Novartis Institutes for BioMedical Research, said: “Therapy for many types of cancers is expected to rely increasingly upon rational combinations of agents.

“Immunotherapy agents provide additional arrows in our quiver for such combinations. They complement our extensive portfolio of drugs that hit genetically-defined cancer-causing pathways, and also may be relevant to expansion of CAR therapies.”

CoStim did not respond to LSIPR’s request for comment. n

novartis boosts cancer immunotherapy research

Focusing on research



leverkUsen, germany

Bayer will acquire Norwegian pharmaceutical company Algeta for €2.1 billion ($2.9 million), it announced this month.

Algeta sells cancer treatment Xofigo (radium-223 dichloride), which it has been promoting with Bayer in the US. Bayer Healthcare, a Bayer subsidiary, has the full rights to sell Xofigo outside the US.

Bayer put in an offer for Algeta in November last year. On February 24, the offer period (the time in which the offer must be accepted) was extended to February 26.

Algeta and Bayer have been jointly developing Xofigo since 2009. The US FDA approved the drug in May last year. Bayer received European marketing authorisation for it in November.

Bayer said that all regulatory approvals related to the Algeta transaction have been obtained, but the offer is still subject to certain closing conditions.

When contacted by LSIPR, Bayer said that it had no further comment about the transaction. n

bayer set to complete algeta acquisition

Salix cleared of contract breach allegationsa New york jury has decided that North Carolina-based Salix Pharmaceuticals did not breach its contract with one of its partners, Napo Pharmaceuticals.

It said that Salix had complied with its contractual obligations in commercialising fulyzaq, a drug indicated for HIV patients suffering from diarrhoea.

Napo filed the case against Salix at the Supreme Court of the State of New york in 2011 to break its agreement with Salix. It also sought damages of $150 million.

“We are pleased with the verdict and appreciate the thoughtfulness with which the jury approached this case. Salix takes its contractual obligations to its partners very seriously,” Salix’s chief executive Carolyn Logan said.

INBRIEF

Doing the deal

News25


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washington, Dc, Us

The US Chamber of Commerce has criticised India’s “recent pattern of pharma patent denials”, which it says “are not about access to medicine”.

The chamber’s report, released on February 7, aimed to “shine … a spotlight” on “inadequate and ineffective” IP protection and enforcement in different jurisdictions, and recommended actions for the US government to take.

It highlighted India as having “particular challenges” and designated it as a “Priority Foreign Country”, which makes it subject to investigation.

“Over the last two years, the IP environment in India has deteriorated rapidly,” the report said.

According to the chamber’s International IP Index, which measures the IP environment in 25 countries around the world based on international standards and best practice, India has “the weakest IP environment of all countries”.

It said that India’s policies are “clearly discriminatory”, and laments that other countries including South Africa, Brazil and China are closely monitoring this “Indian IP model”.

It focused on the recent denials of patents on pharmaceutical products that were deemed patentable in other jurisdictions. It referenced one product that was denied by India’s Supreme Court, even though it had been patented in 40 other jurisdictions.

“India’s actions are not about access to medicine,” the report said.

“In many of these cases, the drug maker gave the drug to Indian consumers either free of charge or at a greatly reduced cost. In the case of Glivec, Novartis provided the leukaemia drug to 95 percent of the 16,000 patient population for free, while the remaining 5 percent was heavily subsidised,” it added.

“The annual cost for Glivec generic treatment is approximately $2,100 or three to four times the average annual income in India. Thus, it is actually more expensive for Indian patients to obtain access to these medicines after the patent revocation than it was before.” n

us chamber of commerce slams indian patent practices

Indian government declines to meet USITC officialsThe Indian government has decided not to meet officials from the uS International Trade Commission (uSITC), according to The Economic Times.

“uSITC officials are coming to India and they have sought meetings with officials of different ministries, including commerce and industry, finance and external affairs. but India has decided not to entertain them,” an official said.

“The country’s IPr laws are fully compliant with international laws including WTO [World Trade Organization]. If they have any issues with our laws, they can raise that in the WTO and at that forum we can have consultations with them,” the official continued.

The uSITC has accused India’s IP laws of discriminating against uS pharmaceutical companies. This month it held a hearing on the country’s trade investment and industrial policies.

Takeda files patent infringement case against LupinJapanese companies Takeda Pharma and Tenjin Pharma have filed a patent infringement case against uS-based Lupin Pharma.

The case, filed at the uS District Court for the District of Delaware, relates to uloric, a drug that lowers uric acid levels in sufferers of gout.

Tenjin owns the patent covering uloric, which it has licensed to Takeda for marketing in the uS.

“as litigation is pending, Takeda does not wish to comment beyond stating we will defend uloric patents,” a spokesperson for Takeda told LSIPR.

INBRIEF

Not about access

Rejection

new jersey, Us

Pharmaceutical company Merck and Samsung Bioepis, a joint venture between South Korean firm Samsung and Biogen, have agreed to work on a diabetes treatment.

The firms will develop, manufacture and commercialise MK-1293, an insulin glargine (insulin analogue) candidate for treating patients with type 1 and type 2 diabetes. Phase III clinical studies in type 1 and type 2 diabetes will begin soon.

“We look forward to collaborating with Samsung Bioepis on this insulin glargine candidate, as diabetes is a top priority for the company,” said Matt Strasburger, senior vice president, diabetes, global human health at Merck.

“Merck is strengthening its leadership in diabetes through our own work and in collaboration with others, and this agreement will help build our portfolio across the spectrum of the disease,” he added.

Christopher Hansung Ko, chief executive of Samsung Bioepis, said: “Samsung Bioepis is very pleased to extend the partnership with Merck to the field of diabetes. This collaboration will bring better access to patients with diabetes worldwide.”

Under the terms of the agreement, the companies will collaborate on clinical development, regulatory filings and manufacturing. If approved, Merck will commercialise the candidate.

The collaboration builds on an agreement made by the two companies in February 2013 to develop and commercialise multiple biosimilar candidates. n

Merck and samsung bioepis agree diabetes deal

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Jubilant Biosys expands drug discovery alliance with Janssenbangalore-based Jubilant biosys, a subsidiary of Jubilant Life Sciences, has expanded its drug discovery alliance with Johnson and Johnson-owned Janssen Pharmaceutica in belgium.

first established in 2011, the companies’ collaboration had the aim of delivering preclinical candidates to Janssen for potential development and commercialisation. The new agreement includes multiple therapeutic areas following Jubilant’s diversification.

Most research will take place at Jubilant biosys in India, with some at the Jubilant Discovery Center in the uS.

“We are pleased to announce the expansion of the Janssen-Jubilant collaboration and look forward to discovering novel chemical entities that address the unmet medical needs in these important disease areas,” said Jubilant’s president of global drug discovery services, Subir basak.

Evolva signs cosmetics agreement with L’Oréalevolva Holding, a Swiss company that uses fermentation to make products for the health and nutrition industries, has signed a collaboration agreement with L’Oréal to co-develop novel biosynthetic production routes for an undisclosed ingredient that has “broad applications in the cosmetics industry”.

The companies will use evolva’s fermentation technology platform to develop yeast strains to create a sustainable, cost-effective production of the ingredient.

The collaboration has begun immediately and is due to conclude in late 2016, although it includes an option to expand the ingredient focus.

under the terms of the agreement, L’Oréal will pay evolva research fees, and evolva may receive payments based on the achievement of research objectives.

INBRIEF

Paying research fees

salt lake city, Us

Myriad Genetics has entered into a definitive agreement to acquire inflammatory and autoimmune diagnostics company Crescendo Bioscience for $270 million.

The transaction is due to close by the end of Myriad’s fiscal year 2014 and depends on regulatory approval.

Under terms of the agreement, Crescendo will keep its name and operate as a wholly owned subsidiary of Myriad Genetics.

In a statement on its website, Myriad said that it sees the deal as a “major growth opportunity”, and that the acquisition will complement its current disease focus which includes products in oncology, women’s health, urology and dermatology.

It said that Crescendo’s core product Vectra DA, which tests for rheumatoid arthritis disease activity in patients, represents a $3 billion global market opportunity. More than 1.5 million people in the US suffer from rheumatoid arthritis.

“Crescendo Bioscience fits well into our diagnostic portfolio that is focused on saving lives and improving the quality of life of patients across major diseases,” said Myriad chief executive and president Peter Meldrum.

“Crescendo has pioneered protein-based diagnostics for monitoring disease activity in patients with rheumatoid arthritis and this acquisition diversifies our business into a new high growth, multibillion dollar market opportunity. We are pleased to welcome the 130 employees of Crescendo to the Myriad team and look forward to the impact of this innovative and dedicated group on our organisation.”

President and chief executive of Crescendo William Hagstrom said: “Crescendo has built a strong and growing position in the rheumatoid arthritis diagnostic market, and I believe Myriad will enable us to move to the next level in terms of scale and growth.

“We envision multiple opportunities over the next several years where, as a combined company, we can expand our presence into international markets and provide new innovative products that help improve the lives of patients suffering from autoimmune diseases.”

A spokesperson for Myriad told LSIPR: “At this time, we have publicly disclosed that Crescendo is pursuing a broad IP strategy with patent filings on its testing methods and biomarker algorithms that when issued will extend into the 2030s.” n

us district court invalidates Megace patent

Myriad to acquire crescendo

Ruling for TWi

marylanD, Us

The US District Court for the District of Maryland has ruled that Taiwanese company TWi Pharmaceuticals’ generic version of Par Pharmaceuticals’ Megace ES drug does not infringe US patent 7,101,576.

Megace ES (megestrol acetate) is used in the treatment of appetite loss, severe malnutrition or unexplained significant weight loss in AIDS patients. Since 2005, Megace ES has made more than $600 million in net sales.

Par filed the case in September 2011 to stop TWi from launching a generic version of the drug.

On February 21, the court found the patent to be invalid on the grounds of obviousness. TWi may now launch a generic version of the drug pending approval from the US FDA.

TWi told LSIPR that it is pleased that the judge ruled in its favour.

“As the first applicant to file the ANDA for Megace ES, TWi may be entitled to 180-day generic market exclusivity,” it said in a statement. n



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IP StRategy14 LSIPR Newsletter 02:14


LSIPR Newsletter 02:14 IP StRategy 15


There’s no shortage of drugs formulated with antibodies derived from people or from mice. But California-based Apexigen has

turned elsewhere, developing treatments with antibodies derived from rabbits.

Rituxan (rituximab) and Herceptin (trastuzumab) are just two examples of drugs that use antibodies derived from mice or humans, or humanised antibodies derived from mice. However, rabbits can generate a much broader diversity of antibodies for a target than a mouse, a human or many other species, says Mark Nevins, vice president of business development at Apexigen.

Using a process called gene conversion, rabbits’ immune systems can create antibodies that are generally of a higher quality, and have greater affinity, creating a stronger bond between the antibody and the antigen.

Rabbit-derived antibodies are also effective against targets that many other therapies cannot see, and therefore bind to.

Against this background, Apexigen is currently working on seven different programmes and is “aggressively” pushing forward its lead cancer programme APX005, a humanised monoclonal antibody that received $20 million in financing in August.

Apexigen has a variety of related patents and Nevins says that thanks to the novelty of its

products it doesn’t expect many difficulties getting claims for its antibody programmes.

First isolated in the 1970s, monoclonal antibodies have been heralded as a new hope for cancer therapy. With the capacity to be grown indefinitely, monoclonal antibodies mimic antibodies the body uses in immune response.

Many monoclonal antibodies work by binding to specific antigens and making them more visible to the immune system, while some can slow or stop the growth of a tumour by blocking growth signals from proteins, which attach to receptors on the surface of normal cells.

Other monoclonal antibody-based treatments deliver radiation or chemotherapy to cancer cells, for targeted therapy.

According to the Mayo Clinic, treatments using monoclonal antibodies generally have fewer side effects than traditional chemotherapy treatments.

The US Food and Drug Administration approved the first monoclonal antibody, muromonab, for human use in 1986. Muromonab is indicated to reduce acute rejection in patients who have undergone organ transplants. There have since been around 30 more monoclonal antibody therapies approved, many as cancer treatments, with hundreds more in clinical trials.

combating disease: apexigen using rabbit antibodiesApexigenusesantibodiesderivedfromrabbitstodeveloptherapiesfordiseasesthataredifficulttotreat. LSIPRfoundouthowitprotectsitsnoveltechnologies.



IP StRategy16 LSIPR Newsletter 02:14


historyApexigen was established as an independent company in July 2010 after being spun off from Epitomics, a firm that makes and uses rabbit antibodies in research. Epitomics was subsequently acquired by Abcam.

It has an exclusive licence from Epitomics to use the antibodies as therapeutic agents, and develops technologies in two main areas: rabbit hybridoma, the process of creating hybrid cell lines to culture monoclonal antibodies, and the rabbit antibody humanisation process, which makes the antibodies suitable for use in humans.

Epitomics continues to use the technology for its service business. But “we own all the rights to therapeutic use and we use them as a service provider,” Nevins says.

“We employ Epitomics to do a lot of our lab work, such as antibody discovery work. We’re operating on a virtual model, and rely both on them and other contract labs,” Nevins says.

Apexigen’s seven humanised monoclonal antibody programmes are aimed at developing treatments in oncology, inflammatory disease and ophthalmology.

For four of these programmes, it is collaborating with Chinese biotech firms Simcere Pharmaceutical Group, 3SBio, Jiangsu T-mab Biotechnology and Shanghai Duyiwei Biotechnology.

“The Chinese partners have responsibility to develop and commercialise the product in China—we lend them assistance as they need it,” Nevins says.

Apexigen is also licensing out the use of its antibody platform. It has three partnerships in place: one with Janssen Biotech, another with Alcon, Novartis’ eye-care unit, and another with an undisclosed pharmaceutical company. These are using Apexigen’s technologies to develop their own treatments: “We are always interested in doing more antibody technology deals,” Nevins says.

competitionApexigen’s patents cover the rabbit hybridoma fusion partner technology and the antibody humanisation process. Has it been challenging securing patents on these technologies?

“It’s certainly become a more crowded field over the last number of years,” Nevins says. However the novelty of the product has certainly worked in Apexigen’s favour.

“Since we are one of the few using rabbit-derived humanised antibodies, we haven’t seen

and don’t expect to see a lot of difficulties for getting claims for our antibody programmes.”

According to IMS Health, by 2016 global spending on biologic medicines will reach $200 billion, up from $157 billion in 2011. Spending on biosimilars will account for two percent of this figure, a five-fold increase in the same time period.

In addition, with the introduction of the Patient Protection and Affordable Healthcare Act in the US, the use of biosimilars is being actively encouraged.

But with so little clinical experience with rabbit-derived antibodies in the literature, Nevins isn’t concerned about emerging biosimilar competition affecting Apexigen’s work.

“There is not a long clinical track record for the performance of rabbit antibodies compared with others,” he says.

In addition, the method of scaling up the production has been tried and tested: “The CMC [chemistry, manufacturing and control] processes for scaling up are very similar to those for other antibodies, so there are no difficulties there,” Nevins says.

There are enough data to show that there aren’t any toxicities or untoward effects caused by rabbit-derived antibodies, as opposed to mouse- or human-derived antibodies, he adds.

However, information about the different antibodies’ performance in the human body, and what the body does to the drug after administration, is, for the time being, thin on the ground, leaving little for biosimilar firms to work with.

“In terms of trying to develop a biosimilar you want something that’s going to perform very similarly, so you would probably have to use a rabbit antibody to get a biosimilar, unless you want to spend an awful lot of time tweaking a mouse antibody to perform like a rabbit’s,” Nevins says.

pipelineApexigen will file an Investigational New Drug (IND) Application in the US on APX005 soon, and Nevins expects clinical trials to start in the near future. The firm has hired Boehringer Ingelheim as its contract manufacturer for its clinical trials.

“APX005 is a CD40 agonist, so it activates an immune response against tumours—we’re very excited about it,” Nevins says.

As well as boosting the body’s immune system to fight cancers that are difficult to treat, such as pancreatic cancer, the drug has also shown the potential to kill tumours directly.

The other drugs in Apexigen’s pipeline are either partnered or due to be partnered with firms in China for development.

“We believe the best use of our technology is going to be to go after some of the more difficult targets—targets that companies want to be able to develop antibodies against, but have been frustrated with using other technologies,” he says.

Some proteins are difficult to generate antibodies against because of their structure, Nevins explains. The GBCR class of receptor, for example, has small transmembrane loops that the antibody binds to, though “there’s not very much there for the antibody to see”.

So far Apexigen’s partners have filed four INDs for products using its proprietary technologies—two of which are currently in phase I testing by its partners.

Just two rabbit-derived antibodies are going through clinical trials at the moment, Nevins says, each created by companies that generate antibodies from other animals as well as rabbits. But given the potential of this new technology, he predicts more rabbit-derived antibodies going through the clinic in the near future, creating new options for patients suffering from the most difficult to treat cancers. n

“Apexigen’s patents cover the rabbit hybridoma fusion partner technology and the antibody humanisation process.”

Little clinical experience



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18


exPeRt commeNt LSIPR Newsletter 01.14

RecentCJEUdecisionsonSPCshavebroughtlittleclaritytothe

meaningof‘product’,andarecentAdvocateGeneralopinionin

Bayer CropScience AGthreatenstomuddythewatersevenfurther,

saysPaulEngland.

There has been a considerable amount of activity in the Court of Justice of the European Union (CJEU) recently on the subject of

supplementary protection certificates (SPCs). A number of rulings have come down, and others have been referred to the court. Some of these have concerned what ought to be regarded as one of the most simple elements of the legislation: what is meant by a ‘product’, as defined, for the purpose of being capable of protection by an SPC?

But this question has proved to be anything but simple. This is unfortunate, because if something qualifies as a ‘product’ then it is potentially capable of up to five years’ additional exclusivity protection when the patent that protects it expires.

The recent rulings from the CJEU on products have concerned SPC protection for medicinal products, under Regulation (EC) No 469/2009 (the medicinal SPC regulation). These have been controversial. The reason is that under earlier authorities it had been understood that a product, as the regulation itself stipulates, is restricted to an active ingredient or combination of active ingredients. As a result, products which are, for example, new salts of previously authorised active ingredients are not capable of SPC protection.

However, this consensus was disrupted in July 2012 by the CJEU’s controversial Neurim decision. Neurim concerns an application for an SPC on the basis of a marketing authorisation (MA) and a patent for use of the active ingredient circadin-melatonin in the treatment of insomnia in humans. The same active ingredient had previously been authorised for improving the reproductive activity of sheep in the veterinary product Regulin.

The question therefore arose of whether the MA for Regulin meant that the product was the subject of an earlier MA, thereby preventing the grant of an SPC for circadin-melatonin for the new use. The CJEU ruled that it is possible to obtain SPC protection for second medical use products even when the active ingredient at issue has already been the subject of an earlier MA. The reasoning of the decision was based largely on the understanding that the SPC regulation is intended to protect the investment made in pharmaceutical research to discover new therapeutic uses of products.

Soon afterwards, and relying in part on the investment argument that was successful

the equivalent of an ‘active ingredient’ in the medicinal SPC regulation.

The substance in question in Bayer CropScience AG is a safener called isoxadifen. Safeners are defined in the Plant Protection Products Regulation 1107/2009 (the PPP regulation) as “substances or preparations which are added to a plant protection product to eliminate or reduce phytotoxic effects of the plant protection product on certain plants”. But, under the PPP regulation, safeners are not regarded as active. Indeed, the same regulation defines ‘active substances’ differently, although the use of both must be approved in the same way under the PPP regulation.

Furthermore, as with the medicinal SPC regulation, CJEU rulings so far on ‘active substances’ have been strictly construed to mean compounds that act on harmful organisms, plants, parts of plants or plant products.

In his opinion in Bayer CropScience, the AG now casts doubt on a generally applicable, strict reading of ‘active substance’. First, in his opinion, the term ‘active substance’ in

in Neurim, GSK Biologicals sought an SPC on an adjuvant to a vaccine (GSK Biologicals [C-210/13]). However, in this case, the CJEU ruled that an adjuvant cannot be properly regarded as an active ingredient, because it merely assists the working of a vaccine, rather than having activity itself. An adjuvant is therefore not a ‘product’ for the purpose of the medicinal SPC regulation. The court also affirms the Neurim decision, but appears to try to draw a line under it as a special case.

similar questions As if the law in this area had not become unsettled enough, an opinion of Advocate General (AG) Niilo Jääskinen has now been published in Bayer CropScience AG (Case C-11/12), a case decided under the related Regulation (EC) No 1610/96 concerning SPCs for plant protection products. It is related legislation because both regulations are concerned with SPCs and are drafted similarly. Hence, as the AG remarks, rulings on the medicinal SPC regulation can be used to elaborate the interpretation of Regulation 1610/96. In this case the AG was addressing the similar question of what an ‘active substance’ is,

spcs: the siMplest

issue is in doubt

LSIPR Newsletter 02:14 19


exPeRt commeNt

same product and the subject of a single MA (as here), by granting an SPC for one of them—the herbicidal ingredient—and not the other—the safener.

It remains to be seen how the CJEU will rule on this issue. As a rule of thumb, the CJEU follows the opinion of the AG, but by no means always. With the somewhat inconsistent, some would say erratic, decision-making that has characterised rulings from the CJEU in the area of SPCs, no presumptions can be made.

However, by issuing an opinion that a safener may qualify as an active substance, in particular the reasoning (i) that a substance could qualify as an active ingredient; (ii) that investment is a factor in this; and (iii) by virtue of an indirect action—apparently at odds with the decision under the medicinal SPC regulation in GSK Biologicals—the rules on SPCs are once again thrown into doubt on the simplest issue. n

Paul England is a senior associate at Taylor Wessing LLP. He can be contacted at: [email protected]

mechanism or activity of the substance at issue that should be taken into account to determine whether it is an ‘active substance’. Ultimately, this is an issue of fact for the national court to determine.

However, the reasoning of the AG then becomes more subtle and potentially significant in understanding what an active substance is and, by analogy, what an active ingredient is under the medicinal SPC regulation. The AG suggests that the definition of active substance should not be limited to substances which merely act directly on harmful organisms for the purpose of plant protection. Instead, the AG indicates that an active substance should also include substances that trigger a chemical or biological pathway within a plant which results indirectly in such protection.

What about the Neurim case? This case is not referred to by the AG, but its influence is clear: given the economic purpose of SPCs to encourage innovation by lengthening exclusivity protection, it would be somewhat artificial, the AG says, to distinguish between two or more substances that are patented, included in the

“TheAGsuggeststhatthedefinitionofactivesubstanceshouldnotbelimitedtosubstanceswhichmerelyactdirectlyonharmfulorganismsforthepurposeofplantprotection,andthatinvestmentprotectionmatters.”

Regulation 1610/96 is to be interpreted to cover any substance which meets the conditions laid down in Regulation 1610/96, including, where appropriate, safeners. In other words the treatment and definition of an active substance in Regulation No 1107/2009 is essentially irrelevant to how it is to be understood under Regulation 1610/96—the regulation must be understood on its own terms.

However, this seems to be a somewhat circular way of dealing with the issue and leaves open the original question of what an ‘active substance’ is and whether it does include safeners.

As well as expressly drawing the comparison between the two SPC regulations, the AG also refers to the GSK Biologicals SA case (C-210/13) discussed above. The AG recognises that such earlier decisions, both under the medicinal SPC regulation and Regulation 1610/96, must be taken into account. However, at the same time, he emphasises that Regulation 1610/96 must be applied on a case-by-case basis according to the effects of the particular substance at issue.

This requires an analysis in each case to determine whether there is a special

caSe RePoRt20 LSIPR Newsletter 02:14


Beyondpatentenforcement:theHerceptinphoenix

Roche sprung a surprise of sorts at the expense of Indian biopharmaceutical company Biocon and US drugmaker Mylan when it succeeded in securing an interim injunction restraining them from relying upon, or otherwise referring to, Herceptin, Herclon or Biceltis or using any data relating to the drug trastuzumab marketed as Herceptin, Herclon or Biceltis including data relating to its manufacturing process, safety, efficacy and sales.

The injunction extended to any press releases, public announcements, promotional or other materials for their drugs Canmab and Hertraz and stopped them claiming any similarity with Herceptin, Herclon or Biceltis.

Trastuzumab is a $6 billion per year biological drug sold by Roche under the brand names Herceptin, Herclon or Biceltis and is a blockbuster drug for the treatment of human epidermal growth factor receptor 2-positive (HER2+) breast cancer. Roche obtained approval

for import and marketing of trastuzumab in India in 2002 and patent protection for ‘Herceptin’ was also secured under Indian patent 205534, which had a term up to May 2019.

There is interesting history to this drug. The Indian Ministry of Health had mooted the idea of issuing a compulsory license under Section 92 of the Indian Patents Act, 1970, which pertains to compulsory licences in circumstances of national emergency or extreme urgency or public non-commercial use, mainly owing to prohibitive pricing in India. However, in July 2013, the Department of Industrial Policy and Promotion (DIPP) refused to grant a compulsory licence, following which the Ministry of Health recommended the government exercise its powers under Section 66 of the patents statute to revoke the Herceptin patent in the public interest. In a remarkable turn of events, Roche chose to let its Indian Herceptin patent lapse prematurely by not paying the renewal fee. Apparently, pursuant to the lapse

of the Herceptin patent, Biocon and Mylan co-developed a purportedly biosimilar version of trastuzumab under the brand names Canmab and Hertraz respectively.

IP enforcement of a biological drug is unprecedented in the developing hotbed of Indian IP jurisprudence—big ticket pharma patent battles have so far stuck to the more traditional turf of chemical pharmaceuticals. Biosimilars differ from generic chemical drugs because their active ingredients are huge molecules with intricate structures which are almost impossible to replicate in minute detail. A biosimilar drug is similar to the innovator biopharmaceutical product only in view of the structural and manufacturing complexities involved in the production of biopharmaceuticals. Due to the unique starting material and complex manufacturing processes, it is not possible to precisely reproduce a biological in the same way a pharmaceutical chemical generic can be reproduced.

WhileWesternpharmaceuticalcompaniesstruggletoenforcetheirIPrightsinIndia,Rochehastakenanunorthodoxbutsurprisinglyeffectivestance,asDebashishBanerjeeandShukadevKhuraijamexplain.

LSIPR Newsletter 02:14 caSe RePoRt 21


In the matter at hand, Roche’s argument was two-pronged. Its first allegation was that Biocon and Mylan were allegedly misrepresenting their drugs as “trastuzumab”, “biosimilar trastuzumab” and a “biosimilar version of Herceptin” without following the due process for their drugs being approved as biosimilars in accordance with the Guidelines on Similar Biologics issued in 2012. The second limb of its challenge accused Biocon and Mylan of passing off their goods as “Trastuzumab”, “biosimilar Trastuzumab” and a “biosimilar version of Herceptin”. The Drug Controller General of India (DGCI) was also made a party to the suit for giving permission to Mylan and Biocon to launch Canmab and Hertraz.

The guidelines prescribe specific standards for the development and evaluation of biosimilar biologics and seek to ensure the comparability of safety, efficacy and quality between the innovator biologic and the biosimilar molecule, prior to approving the latter as a biosimilar product. A “similar biologic” is defined thus: a “biological product/ drug produced by genetic engineering techniques and claimed to be ‘similar’ in terms of safety, efficacy and quality to a reference biologic, which has been granted a marketing authorization in India by the DCGI on the basis of a complete dossier, and with a history of safe use in India.”

At the first hearing—heard ex parte—Roche contended that all applications for manufacturing and marketing authorisation of similar biologics in India are required to be evaluated under the guidelines and only approved products may be represented as biosimilar products. Roche argued that Biocon’s and Mylan’s approvals could not be said to have satisfied the requirements for a biosimilar drug under the guidelines, because the protocol and design study for Canmab was filed and approved by the DCGI prior to the guidelines becoming effective. Further, the approval had had been granted very quickly which made a weak case for compliance with the guidelines.

Roche also drew the court’s attention to the fact that there was no publicly available record of registration of Phase I and Phase II clinical trials by Biocon and Mylan for the “purportedly biosimilar trastuzumab”. This clearly contravened an official notification effective June 15, 2009, stipulating that

registration of all phases of a clinical trial with the Clinical Trials Registry in India was mandatory prior to the initiation of any such clinical trials.

Roche sought to restrain Biocon and Mylan from introducing their drugs to the Indian market as biosimilar products, until appropriate tests and studies prescribed under the guidelines were conducted and appropriate approvals obtained.

In addition, Roche also sought to restrain Biocon and Mylan from using its trademark Herceptin and the reputation and goodwill attached to it.

After hearing the arguments, Biocon was directed by the court to disclose the nature of approvals it had obtained for its biosimilar product at the time of the next hearing, which was fixed for February 28, 2014. Further, the court agreed with Roche that the misrepresentations made by Biocon and Mylan by referencing the brand name Herceptin amounted to passing off since the latter companies’ impugned statements alleged their drugs were of the same safety, efficacy and quality as Herceptin. These misrepresentations were likely to deceive patients, the court found. It held that Biocon and Mylan were likely to derive unfair advantage from the reputation and goodwill enjoyed by Herceptin, and that Roche would suffer prejudice and irreparable injury if an interim order were not passed in the matter. It therefore granted the injunction, pending the February 28 hearing.

Biocon and Mylan responded swiftly and challenged the order by filing appeals before the Division Bench (two judge bench) of the Delhi High Court. After hearing the appeals, the bench directed they be treated as

applications and listed before the same judge who had granted the injunction. When the applications were heard, Biocon and Mylan conveyed that they would forbear from using the trademarks Herceptin, Herclon or Biceltis in any press releases or public announcements for their drugs Canmab and Hertraz. However, Biocon and Mylan pressed for modification or vacation of the earlier order in view of the hardship it was causing them, given the drugs in question had already been launched.

The primary bone of contention at the hearing was whether Biocon and Mylan were entitled to use the package insert currently in circulation while marketing their drugs in the country. It was their contention that the package insert was duly approved by the Drug Authority, making it fit for use while marketing the drugs in question, unless the approval was first revoked by the Drug Controller.

Roche argued against the use of the package insert since no approval had been granted by the Drug Controller for the package insert per se. It asserted that Biocon’s package insert slavishly reproduced its own package insert, albeit with various misrepresentations. While Biocon had submitted evidence to prove that the label, carton and package insert were submitted to the Drug Controller, no document established that the package insert in question had been specifically approved.

Weighing the circumstances, the court allowed Biocon to use the package insert in question until the February 28 hearing, with the caveat that it should have the necessary approval of the package insert in the first place. The court clarified that if the approval had not been obtained, the interim order passed earlier would continue without modification.

Biocon and Mylan would have not seen this action coming. The proceeding is significant in that it heralds something unparalleled in the area of biologic drugs enforcement. It remains to be seen whether Roche is triumphant with a confirmatory order or whether Biocon and Mylan manage a reprieve. n

Debashish Banerjee is a managing associate at Remfry & Sagar. He can be contacted at: [email protected]

Shukadev Khuraijam is a partner – designate at Remfry & Sagar. He can be contacted at: [email protected]

“Theprimaryboneofcontentionwas

whetherBioconandMylanwereentitled

tousethepackageinsertcurrentlyincirculation.”

22 LSIPR Newsletter 02:14


exPeRt commeNt

By order dated December 5, 2013, the Court of Appeals in Düsseldorf (docket no. I-2 U 68/12) referred various questions to the Court of Justice of the European Union (CJEU). The court asks for guidance on whether (and under what conditions) the supply of patented compounds by a third party to a (domestic) generic company, which

authorisation. European pharma legislation (Directives 2004/27/EC and 2004/24/EC) provides for respective EU-wide provisions that shield the generic company from being held liable for patent infringement when using the compounds / substances for these purposes (so-called “Bolar exemption”). The EU member states have incorporated the

the Bolar exemption: thequestionofthirdpartiesAnewreferraltotheCJEUshouldshedlightontheextentoftheso-calledBolarexemptioninEurope,saysBerndAllekotte.

intends to use the compounds for obtaining a marketing authorisation for a generic drug, is covered by the Bolar exemption.

legal backgroundGeneric companies are allowed to use a patented compound / substance in the studies and trials that are required for obtaining a marketing

LSIPR Newsletter 02:14 23


exPeRt commeNt

“ThroughoutEurope,thesamerulesshouldapply.Itishardlyacceptablethatthirdpartydeliveriesareexemptinonecountry,butheldtoinfringeinanother.”

2. If this is to be answered in the affirmative:

a) Does the privilege status of the third party depend on whether the delivered compound is actually used for privileged studies / trials, or does it depend on whether the third party may assume that they are used accordingly?

b) Is the party obliged to take precautions that the substance is indeed used for privileged studies / trials? Or do the precautionary measure differ, depending on whether the substance is merely offered or actually delivered.”

[Questions abbreviated by the author]

implications in practiceIt would seem that the Court of Appeals in Düsseldorf correctly regards the wording of Sec. 11 no. 2b German Patent Act (which is, in essence, identical to the wording of Article 10 par. VI Directive 2001/83/EC) to be unclear with respect to deliveries of third parties. Whether and under what conditions such deliveries may benefit from the privilege has been discussed for years.

It should be noted that the Court of Appeals in Düsseldorf endorses, at least in general, that such deliveries may benefit from the privilege. However, the court says it is necessary to safeguard that the compound is actually used for the privileged studies and trials.

The decision of the CJEU will be important for the pharmaceutical market in the EU. Often, generic companies are dependent on supplies of APIs from third parties. This is particularly true for midsized generic companies that cannot manufacture the compounds by themselves. But there are also relatively big generic companies that have compounds delivered from third parties.

Whether supplies of patented compounds are permitted under the Bolar exemption remains unclear until now. Throughout Europe, the same rules should apply. It is hardly acceptable that third party deliveries are exempt in one country, but held to infringe in another. This would lead to significant competitive advantages for certain EU member states over others, which is contrary to what EU-Directives 2004/27/EC and 2004/24/EC aim at. Therefore, the referral should be welcomed. A decision is expected in 2015. n

Dr Bernd Allekotte is a partner at Grünecker. He can be contacted at [email protected]

benefit from the exemption according to Sec. 11 no. 2 German Patent Act.

This part of the decision is hardly surprising.

Second, with respect to the Bolar exemption (which is contained in Sec. 11 no. 2b German Patent Act), the decision of the Court of Appeals in Düsseldorf ’s decision is long overdue.

As noted above, in Germany, the Bolar exemption relates to:

“Studies and trials and the respective practical requirements that are necessary for obtaining drug authorisation for the bringing into commerce in the European Union or for obtaining drug authorisation in the EU member states or in third countries.”

What is not addressed explicitly in this provision is whether deliveries of third parties—and if so under what conditions—may benefit from the exemption. Against this background, the Court of Appeals Düsseldorf refers the following questions to the CJEU:

“1. Must Article 10 par. 6 of Directive 1/83 EC be interpreted as meaning that acts of delivery from a third party are also covered, ie, exempted from patent protection, if such third party offers a patented active substance to a generic company, which uses it to obtain market authorization according to Article 10 par. 6 of Directive 2001/83 EC?

respective provisions in their national laws. However, it is undecided whether not just the generic company, or also third parties that supply a patented substance / compound to the generic company, may benefit from the Bolar exemption.

düsseldorf caseIn the case at hand, a third party domiciled in Poland shipped and offered patented compounds into Germany. Upon being sued, it provided the plaintiff / patentee with a cease and desist declaration with respect to any offering and sale of the patented compound. However, it expressly carved out any deliveries and offers of the compound if they served for “test purposes”.

In first instance, the District Court in Düsseldorf held that this supply by a third party was exempted by the (German) Bolar provision only under very limited conditions. According to the court, the third party needed to act as co-organiser of the trials and studies carried out in order to be exempt. It would not suffice for the third party to know that its customer intended to conduct trials and studies, nor for the third party to put its customer under a contractual obligation to use the delivered compound just for these purposes. In the case at hand, the third party was held to not benefit from the Bolar exemption by the district court.

The Court of Appeals in Düsseldorf discussed two exemptions that may apply under German law: first, whether the delivery of the third party may be privileged under Sec. 11 no. 2 of the German Patent Act, relating to trials conducted by the customer. However, this provision only applies if the trials relate to the patented invention. In the case at hand, the customer wanted to conduct bioequivalency studies (which are usual for generics seeking to bring their products to market based on the authorisation for the original). Such studies aim at proving that two drugs that contain the same active pharmaceutical ingredient (API), but differ with respect to their manufacturing process and / or the compounds contained, can be substituted without any risk to the patient.

Therefore, such studies do not aim at findings regarding the patented compound, but serve the sole purpose of establishing that the generic drug has the same (reliable) effect as the original. Therefore, the studies and trials conducted by the customer were held not to

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