january 2014 august 2014 newsletter - life sciences ip review · simon 10 hospira challenges...

Great expectations

Protecting therapies developed from

placenta cells4

January 2014

newsletterSouth AfricAn Pr effortS SPArk drug controverSy

generic krkA to receive dAmAgeS in Nexium cASe

cASe rePort: SuPreme court reverSeS medtroNic ruling

ASSociAtion focuS: biotecanada

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news and intelligence from life sciences intellectual property review

Page 18

hive mentality: Susana Soares and open source research

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AUGUST 2014

HUMIRA PATENT STILL INVALID

ZYDUS SUED TO PROTECT NEXIUM

MYRIAD/MAYO GUIDELINES ATTACKED

MAPPING THE IP LANDSCAPE

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102217 LSIPR Advert:Layout 1 09/04/2014 16:21 Page 1

LSIPR Newsletter 08:14 EDITOR’S LETTER/CONTENTS 3

www.lifesciencesipreview.com

Life Sciences IP Review is published by: Newton Media Limited Kingfisher House, 21-23 Elmfield RoadBromley, Greater LondonBR11LT, United Kingdom Telephone: +44 203 301 8201Director Nicholas LipinskiPublisherPeter GarnerTelephone: +44 203 301 8217Email: [email protected] Managing editorMartin Essex Telephone: +44 203 301 8211 Email: [email protected] editorLeonie MercedesSub-editorRos BromwichJournalists Ed Conlon, Max WaltersEditorial assistantDavid BrookeConsultantJohn HaleyProduction 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)

Personalised partnershipsOur expert comment this month looks at personalised medicine, but more from a business point of view than a medical one. As LSIPR readers will know, personalised medicine is all about tailoring treatment to the individual, and that, of course, can be extremely complicated.Partnerships therefore make sense, bringing together experts in a variety of fields: not just medical specialists but others who know about technology, business and, of course, IP.That’s because personalised medicine can be technologically challenging, and therefore expensive. If there’s a gap in knowledge internally, it may well make sense to bring someone in from outside. And while costs may be high, opportunities for exploiting discoveries may be too—which is where the business specialists and the patent lawyers come in.Perhaps not surprisingly, there was a substantial increase in personalised medicine patent activity in the years up to 2004. And activity has remained at a high level since, although it seems to have levelled off since 2006.So commercial interest in personalised medicine remains high and the importance of partnerships between the scientists, the accountants and the lawyers clear.Pluristem, the company whose IP strategy we look at this month, currently holds 30 patents, issued by the US, EU and countries including China, Russia and South Africa. It also has 120 applications pending.It has a number of trade secrets as well, and reckons the field it’s operating in—developing therapies using cells from the placenta—is ripe for creating new IP too. Every year it files two to six new patent families, so its IP portfolio is growing all the time.Now, it’s working with the Charité university hospital in Berlin to develop new products, and it has licensing agreements with a range of different companies that develop Pluristem products for specific indications.So Pluristem, like so many others, has recognised the importance of partnerships to ensure that it’s a success from a business point of view as well as a medical one.Martin Essex, Managing editor

Contents4 News 4 Federal Circuit upholds invalidity decision on Humira patent 4 Biotech industry reacts to USPTO’s Myriad/Mayo guidelines 5 FDA issues guidance on biologics’ exclusivity period 5 Akorn settles with FTC to allow VersaPharm merger 6 Sanofi and MannKind strike Afrezza deal 6 Merck fined $1.8m for ‘anticompetitive’ generic drug scheme 7 New Jersey court blocks Actavis’s generic Gralise 8 Celltrion files for FDA approval for Remicade biosimilar 8 Federal Circuit judges split on temazepam ‘sham’ case 9 AstraZeneca sues Zydus to protect Nexium 10 Federal Circuit strikes down Apotex patent for ‘inequitable conduct’ 10 Hospira challenges FDA’s ‘unlawful’ approval of Precedex generics 11 FDA accepts generic applications for three-times-weekly Copaxone 12 PhRMA reacts to FDA’s biosimilars guidance 12 Sandoz barred from making Remodulin generic until 2017 13 Forest sues Lupin to protect $1.5bn Namenda14 IPstrategy:Pluristem Great expectations 18 Legalupdate:Myriad/Mayo A hostile response to the USPTO’s guidelines20 Expertcomment:personalisedmedicine Mapping the IP landscape

EDITORIALPANELMaryAnneArmstrong,partner, Birch, Stewart, Kolasch & Birch LLPVictoriaBeniac-Brooks, partner, Marks & Clerk LLPWolfgangBublak, partner, Bardehle PagenbergTrevorCook, partner, Wilmer Cutler Pickering Hale and Dorr LLP GabrielDiBlasi, partner, Di Blasi & AssociatesPaulEngland,Taylor Wessing LLPJanisFraser,principal, Fish & Richardson PCPennyGilbert,partner, Powell GilbertAndrewJenner,director of IP innovation and trade, IFPMAAshwinJulka,managing partner, Remfry & SagarLarsKellberg, corporate vice president, corporate patents, Novo Nordisk A/SJudithKim, partner, Sterne, Kessler, Goldstein & FoxSimonKremer,partner, Mewburn Ellis LLPNathalieMoll, secretary general, EuropaBioMatthewNielsen, partner, Marshall Gerstein & Borun LLPCarolinePallard, partner, Nederlandsch OctrooibureauMichaelPitzner-Bruun, partner, Kromann ReumertNabeelaRasheed, shareholder, McAndrews, Held & Malloy Ltd.JasonRutt, head of patents, RouseJoséTrigueros,partner, Leyva Montenegro Trigueros Abogados SCJoachimWachenfeld, partner, Vossius & PartnerJaneWainwright, partner, Potter Clarkson LLPGordonWright, partner, Elkington & Fife LLP, on behalf of CIPAFranz-JosefZimmer,patent attorney, Grünecker

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Translating Innovation

102217 LSIPR Advert:Layout 1 09/04/2014 16:21 Page 1

NEWS4 LSIPR Newsletter 08:14


WASHINGTON DC, US

The US Court of Appeals for the Federal Circuit has upheld a lower court’s decision that a patent covering rheumatoid arthritis drug Humira (adalimumab) is invalid.

Biopharmaceutical company AbbVie makes and markets Humira, an antibody that can be used either alone or in combination with methotrexate to treat rheumatoid arthritis. It holds the licence to patent 6,270,766, which covers the combination therapy, and expired in 2012.

AbbVie brought the case to the US District Court for the Southern District of New York in 2011 after patent holder The Mathilda and Terence Kennedy Institute of Rheumatology Trust, since renamed The Kennedy Trust for Rheumatology Research (Kennedy), demanded it obtain an additional licence on the disputed patent, 7,846,442, which is due to expire in 2018.

Federal Circuit upholds invalidity decision on Humira patent

Biotech industry reacts to USPTO’s Myriad/Mayo guidelinesVIRGINIA, US

A group of 12 international biotechnology associations has written to the US Patent and Trademark Office (USPTO), raising concerns about the office’s guidelines on determining the patent eligibility of natural products in the aftermath of the Myriad and Mayo cases.

The group, known as the International Bioindustry Associations, represents thousands of businesses, academic institutions and non-profit research centres, and includes EuropaBio, the UK BioIndustry Association, AusBiotech and the Japan Bioindustry Association.

In March this year, the USPTO issued its Guidance For Determining Subject Matter Eligibility Of Claims Reciting Or Involving Laws of Nature, Natural Phenomena, & Natural Products, inviting the industry to comment and make suggestions on the guidance.

In its submission, dated July 31, the group suggested that establishing the guidelines will stymie innovation by disincentivising investment in research and development in biotechnology.

“Internationally harmonised, science-based regulatory and legal frameworks are important for competitiveness and innovation to ensure faster and more equitable access to new biotech products and processes for patients, farmers and consumers around the world,” the letter said.

The group said the guidance will be a “significant departure from internationally accepted norms of patentability,” particularly with regard to industrial, agricultural, and pharmaceutical preparations of naturally-derived substances, compositions and processes.

“Inventive preparations based on naturally-occurring substances have historically been of great importance in biotechnology, and innovation in this area has been spurred, at least in part, by the availability of patent protection,” it said.

“By singling out naturally-derived biotechnology inventions for special, disfavoured treatment, the guidance would establish peculiar disincentives for investment in research and development of entire categories of biotechnology.”

According to the letter, the group’s member companies have already received rejections

from the USPTO for patents directed at pharmaceutical formulations having purified naturally-occurring substances as active ingredients, diagnostic laboratory procedures, and other inventions that were neither considered nor discussed in the US Supreme Court’s Myriad and Mayo decisions.

“Such rejections under the new guidance, if they were to become systemic, would seriously impair investment incentives in new, socially beneficial technologies.”

A statement on the AusBiotech website said that the US government, along with governments of EU member states and those of other major trading partners including Japan and South Korea, had been working to encourage the adoption of more uniform and consistent rules relating to patents.

Since the USPTO issued the guidelines in March, it has received suggestions from associations including the Association for Molecular Pathology and the American Civil Liberties Union, and from pharmaceutical companies Amgen, Novartis and Novo Nordisk. n See page 18

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It asked for declaratory judgment that claims of the patent were invalid over the ’766 patent for obviousness-type double patenting and the district court agreed with AbbVie and dismissed Kennedy’s claim.

In its appeal to the Federal Circuit, Kennedy argued that although the claims of the ’442 patent are “encompassed by those of the 6,270,766 patent”, the claims of the 7,846,442 were separately patentable.

The 6,270,766 patent is directed towards all individuals in need of rheumatoid arthritis treatment, while the 7,846,442 patent claims treatment of a more “specific patient group”, it said.

The Federal Circuit concluded: “The ’442 patent does not claim a species manifesting unexpected results. The 7,846,442 patent would have been obvious over the 6,270,766 patent.”

Humira is one of the world’s biggest selling drugs. n

LSIPR Newsletter 08:14 NEWS 5


No to Dolly the sheep reviewThe US Court of Appeals for the Federal Circuit has refused to grant an en banc review of its ruling that cloned animals made by methods that produced Dolly the sheep cannot be patented, according to Law360.

In May, the Federal Circuit affirmed a decision by the US Patent Trial and Appeal Board (PTAB), finding that while the method for creating a genetic clone can be patent-protected, the clones themselves may not, as they do not have “markedly different characteristics from any found in nature”.

The patent examiner had rejected claims in the patent in 2008, finding them to be “anticipated and obvious”, which the PTAB later affirmed.

Kilpatrick Townsend appoints new partnerAndrew Serafini, a specialist in IP in the life sciences sector, has joined Kilpatrick Townsend & Stockton LLP.

He joins from Fenwick & West LLP and will work in the firm’s IP group’s health and life sciences team as a partner in its Seattle office.

He has experience counselling biotechnology and pharmaceutical companies on IP strategies, as well as helping them to develop patent portfolios in immunology and molecular biology.

He follows Sean DeBruine, who joined the firm’s patent litigation team in Silicon Valley last month.

“I am looking forward to leading Kilpatrick Townsend’s health and life sciences sector in Seattle,” said Serafini.

INBRIEF

MARYLAND, US

The US Food and Drug Administration (FDA) has issued guidance for biological drug makers about what information they should provide the agency to determine when their products’ marketing exclusivity period should begin, known as the “date of first licensure”.

This date will also determine when biosimilar versions of reference biologic products may be approved by the FDA.

Under Section 351(k)(7) of the Biologics Price Competition and Innovation (BPCI) Act of 2009, brought into force to speed up approvals for biosimilar products, biosimilars may be granted a licence by the FDA 12 years after the reference product’s date of first licensure.

Additionally, an application for approval for a biosimilar product cannot be submitted for review until four years after this date.

The guidance said that the determination of whether a particular biological product

qualifies for a period of exclusivity can “present unique challenges”, because of the scientific and technical complexities associated with larger, more complex molecules, as well as the processes by which they are made.

It said that, in most instances, the date of first licensure will be the date the product was first licensed in the US.

However, there are exceptions. The date of first licensure will not include licensure for supplements for the biological product, or amended applications that include a new indication, route of administration, dosing schedule, or modification to the structure of the biological product that does not result in a change in safety, purity, or potency.

The guidance was issued days after five US senators wrote an open letter urging the FDA to issue guidance on naming conventions for biosimilar products under the BPCI Act.

The senators, who included Orrin Hatch, co-sponsor of the 1984 Hatch-Waxman Act that encouraged the manufacture and use of generic drugs, said that the guidance should be issued as soon as possible.

It noted the FDA’s acceptance of Sandoz’s biosimilar application in July, and asked: “Does the FDA intend to approve the first biosimilar before policies on these key scientific questions are publicly released?” n

FDA issues guidance on biologics’ exclusivity period

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ILLINOIS, US

US-based injections maker Akorn has agreed to sell its rights to develop, manufacture and market generic tuberculosis injection rifampin to Watson Laboratories to settle charges by the US Federal Trade Commission (FTC) that its proposed acquisition of pharmaceutical company VersaPharm was likely to be anticompetitive.

The agreement will see Akorn divesting its Abbreviated New Drug Application (ANDA) for injectable rifampin, which is currently pending with the FDA, to Watson.

Akorn intends to buy VersaPharm for approximately $324 million.

According to the FTC, only VersaPharm and two other companies have FDA approval to sell a generic version of injectable rifampin, and there are no viable substitutes for injectable rifampin as a tuberculosis treatment.

It said that if Akorn’s acquisition of VersaPharm had not happened, Akorn would have been likely to enter the generic rifampin injection market, resulting in a “significant” price reduction for the drug.

By contrast, if the acquisition had gone ahead without the sale of the rifampin rights, the combined company would have probably forgone or delayed the introduction of Akorn’s generic injectable rifampin. n

Akorn settles with FTC to allow VersaPharm merger



Vivus acquires weight loss patents Pharmaceutical company Vivus has acquired a number of patents from Janssen Pharmaceuticals, a subsidiary of Johnson & Johnson, relating to the methods of using topiramate.

Topiramate is an anti-epileptic drug used to treat migraines. Patents ‘537 and ‘220 acquired by Vivus relate to the method of using topiramate to treat obesity and reduce blood glucose.

Janssen had initially filed a lawsuit alleging Vivus infringed patents ‘537 and ‘220 as well as many other patents, but has since dropped the case after the announcement of the deal.

Vivus will pay an up-front fee to Janssen and royalties pertaining to the sales of the drug using the patents.

Biosimilars: ‘big impact in five years’The chief executive of Switzerland-based Novartis has told reporters gathered at its headquarters in Basel that biosimilars will not have an impact on the pharmaceutical market for at least another five years.

According to Reuters, Joe Jimenez, chief executive of Novartis, said: “By the year 2020, which is just five years from now, you’re going to see a big impact.

“In two or three years you’re not going to see a big difference,” he added.

However, he said there will be an “inflection point” in the market in 2017, 2018 and 2019 once a number of antibody drugs lose patent protection in what many commentators describe as a ‘patent cliff’.

INBRIEFPARIS, FRANCE

French pharmaceutical company Sanofi and the US-based MannKind Corporation have entered into an exclusive licensing agreement to develop and commercialise MannKind’s Afrezza (insulin human), an inhalable insulin therapy for adults with type 1 and type 2 diabetes.

Afrezza is an insulin powder to be taken by diabetics before meals through an inhaler. It was approved by the FDA in June, and has 30 patents listed in the Orange Book. Sanofi and MannKind plan to launch the drug in the US in the first quarter of 2015.

Under the agreement, announced on August 11, Sanofi will handle global commercial, regulatory and development activities, while MannKind will manufacture the drug at its Connecticut facility. The companies will also collaborate to expand their manufacturing capacity as necessary.

MannKind, which was profiled by LSIPR last year, will receive an up-front payment of $150 million and potential milestone payments of up to $775 million.

MannKind’s chairman and chief executive Alfred Mann said: “We are so very pleased and honoured that Sanofi has joined with MannKind to bring Afrezza to patients with diabetes worldwide.

BRASÍLIA, BRAZIL

A Brazilian antitrust watchdog is fining German pharmaceutical company Merck $1.8 million for an alleged conspiracy to stop medicine distributors from working with generic drug makers.

Brazil’s Administrative Council for Economic Defence (CADE) ordered Merck to pay the BRL 4.295 million fine for forming a “cartel” with domestic units of large pharmaceutical companies.

According to The Wall Street Journal’s Pharmalot blog, in 1999, Merck met pharmaceutical companies including Bayer; Bristol-Myers Squibb; the now Pfizer-

“Sanofi is the ideal partner given its complementary product portfolio, its vast insulin market presence and a leading global commercial infrastructure. Our profit-sharing agreement aligns the interests of MannKind and Sanofi to optimise development, commercialisation and manufacturing costs.”

Pierre Chancel, senior vice president of Sanofi’s diabetes division, said: “Afrezza is a further addition to our growing portfolio of integrated diabetes solutions. It is uniquely positioned to provide patients with another insulin therapy option to manage their diabetes that does not require multiple daily injections.”n

owned Wyeth; Boehringer Ingelheim; Eli Lilly; Roche; Glaxo Wellcome (now part of GlaxoSmithKline); and Johnson and Johnson.

Merck’s agreement with the drug makers could hamper the entry of generic medicines into Brazil, harming the market and consumers, a statement on the CADE website said.

“The anticompetitive effects in practice are clear,” said CADE commissioner Alessandro Octaviani, who characterised the meeting as an attempt to boycott the Brazilian generics market.

Merck did not respond to a request for comment. n

Sanofi and MannKind strike Afrezza deal

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Merck fined $1.8m for ‘anticompetitive’ generic drug scheme



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PLATO investigation haltedUK-based pharmaceutical company AstraZeneca has announced that an investigation conducted by the US Department of Justice into the platelet inhibition and patient outcomes trial (PLATO), the clinical testing of the Brilinta drug (ticagrelor), has finished with no further action.

Brilinta is designed to treat acute coronary syndrome and was tested in the PLATO trial as part of the Parthenon research scheme, AstraZeneca’s largest ever clinical trial programme.

Allegations of misconduct over its methods of testing the drug prompted an investigation by the US Department of Justice.

INBRIEF

NEW JERSEY, US

The US District Court for the District of New Jersey has ruled that Actavis may not launch a generic version of California-based Depomed’s Gralise (gabapentin), it has been announced.

Actavis had filed an ANDA with the US FDA for approval to market a generic version of Gralise.

The court found that Actavis infringed seven of the patents that cover Gralise, and upheld the patents’ validity. Gralise is covered by nine patents listed in the Orange Book that are due to expire between 2016 and 2024.

Gralise is a tablet used to treat postherpetic neuralgia, ie, pain after shingles. In 2013, it generated sales of $36 million.

Jim Schoeneck, Depomed’s president and chief executive officer, said: “We are pleased with

this decision, as it confirms the innovation of Gralise and the strength of our patents. This ruling provides for nearly ten years of additional market exclusivity.

“We look forward to providing Gralise to postherpetic neuralgia patients and their physicians well into the next decade.”

In April, Depomed settled all litigation with pharmaceutical companies Incepta and Zydus, which were also seeking to launch generic gabapentin tablets before expiration of the Gralise patents. n

New Jersey court blocks Actavis’s generic Gralise

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WASHINGTON DC, US

The US Court of Appeals for the Federal Circuit has affirmed a district court’s decision that pharmaceutical company Tyco Healthcare’s patents directed to sleep aid drug temazepam were not infringed.

It comes after a long-running patent infringement case between Tyco (now Covidien) and generic drug maker Mutual Pharmaceuticals (now part of Sun Pharma).

In a split opinion handed down on August 6, the Federal Circuit also reversed the court’s finding that Tyco is liable for violating antitrust laws, and remanded that part of the case to the US District Court for the District of New Jersey.

However, dissenting judge Newman said

that by reversing the district court’s summary judgment dismissing Mutual’s antitrust claims, the court “creates several new grounds of antitrust liability”.

Tyco sued Mutual for patent infringement after it filed an ANDA seeking approval from the FDA to make and sell a generic version of Restoril (temazepam).

In a counterclaim, Mutual accused Tyco of violating antitrust laws by filing a citizen petition with the FDA in which it urged the agency to change the criteria for determining how bioequivalent the two drugs were. Mutual argued that Tyco’s filing of the petition delayed the FDA’s approval of its temazepam ANDA.

The case of infringement hinged on each of the drugs’ claimed surface areas (a measure of the surface area of a drug per unit of weight).

Mutual claimed in its ANDA that the surface area of its generic temazepam does not fall within the range claimed in Tyco’s patent.

The district court agreed that Mutual’s generic would not infringe Tyco’s patent.

Tyco and Mutual had measured their respective drugs’ surface areas in different ways. Despite this, it does not “convert routine patent litigation into an antitrust cause”, Newman said in her opinion.

“Although Tyco lost on the merits of the case, its Hatch-Waxman suit was not a ‘sham’,” she said.

“Litigation is deemed a ‘sham’ when ‘no reasonable litigant could realistically expect success on the merits’,” she added.” n

Federal Circuit judges split on temazepam ‘sham’ case

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INCHEON, SOUTH KOREA

South Korean biopharmaceutical company Celltrion has applied for approval from the US FDA to market a biosimilar version of Remicade (infliximab), it announced on August 11.

Remicade is a monoclonal antibody (mAb) that is administered intravenously to treat autoimmune diseases including psoriasis, Crohn’s disease and rheumatoid arthritis. Marketed by Janssen, it generated worldwide sales of $6.6 billion in 2013.

According to a statement by Celltrion, the patent for Remicade is not due to expire until the end of 2018. In March, Celltrion filed to invalidate five patents directed to the drug at the US District Court for the District of Massachusetts. The case is still pending.

Celltrion said that it expects Remsima to be the first biosimilar mAb to be filed through the FDA, and the second biosimilar. Last month, Sandoz filed the first biosimilar application with the FDA for approval to make and sell a version of Amgen’s Neupogen (filgrastim).

Celltrion has completed additional clinical trials to determine the bioequivalency of Remicade with Remsima, and said it expects to receive the FDA’s approval of the drug within a year.

Remsima has already received regulatory

Celltrion files for FDA approval for Remicade biosimilar

approval in more than 50 countries, and over the last 12 months has been approved by the European Medicines Agency, Japan’s Pharmaceutical and Medical Devices Agency, and Health Canada.

According to Celltrion, it is the first and only biosimilar mAb to be approved by the regulatory bodies.

In a statement, a Celltrion official said that the company’s application was garnering interest

from biosimilar developers and the healthcare industry “as a whole”.

“The medical community is aware that the eventual approval of sales of biosimilars in the US market will signal an age where biosimilar mAbs are globally recognised as innovative high quality biologics, with equivalency in both efficacy and safety to their originator products, available to patients in need at a more affordable price,” said the statement. n



Physicians ‘concerned about the naming of biosimilars’Physicians representing numerous health organisations have written an open letter to the commissioner of the US FDA saying they are “concerned about the naming of biosimilars”.

Organisations such as the Alliance for Patient Access, the American Academy of Neurology and the American College of Rheumatology have backed a letter sent to commissioner Margaret Hamburg arguing that generic versions of drugs “must have non-proprietary names”.

They write that “distinct non-proprietary names will help to alert physicians that each product, while safe and effective, may differ slightly”.

INBRIEF

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Anglo-Swedish pharmaceutical company AstraZeneca has sued India-based Zydus for infringing three patents related to its heartburn drug Nexium (esomeprazole magnesium).

AstraZeneca filed the case on July 31, at the US District Court for the District of New Jersey, after Zydus submitted an ANDA seeking permission from the US FDA to market a esomeprazole magnesium delayed-release tablets.

In its ANDA Notice Letter to AstraZeneca, Zydus argued that the patents are invalid and unenforceable.

AstraZeneca holds the NDA for Nexium in 20mg and 40mg doses. In the case, it asserts three patents, 6,369,085, 7,411,070 and 8,466,175, that cover the drug’s active ingredient, processes for preparing the drug’s active ingredient, and methods of treating helicobacter infections.

Helicobacter pylori is a bacterium linked to the development of gastritis and dyspepsia.

All three of the asserted patents are due to expire in 2018.

AstraZeneca has asked for a judgment that the patents are valid and enforceable, that Zydus’ ANDA infringes claims in each of the patents, and for a permanent injunction stopping Zydus from making or selling generic esomeprazole magnesium products before expiration of the patents.

Nexium, which is available over the counter in the US, made US sales of $455 million in the second quarter of 2014. n

AstraZeneca sues Zydus to protect Nexium

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ILLINOIS, US

Illinois-based drug company Hospira has sued the FDA, challenging its recent decision to approve generic versions of Precedex (dexmedetomidine hydrochloride).

Precedex is an intravenous sedative used in an intensive care setting. It has one patent listed in the Orange Book, which has been licensed to Hospira by Finnish pharmaceutical company Orion, and is due to expire in 2019.

Filing at the US District Court for the District of Maryland on August 19, Hospira asked the court to enjoin implementation of the decision, which it said was based on a “clear error of law”, and to recall any generic products sold under the decision.

It argued that the decision was an “unlawful application” of the FDA’s authority, as the generic product labels an indication that overlaps with a use covered by the branded product’s patent. The generic must propose a

and suggested that at least six months’ worth of the generic product will reach wholesale distribution channels.

One company has offered the Precedex generic at a price 45% lower than the current brand price, it said.

Mylan has announced the launch of a dexmedetomidine hydrochloride injection. Quoting figures by IMS Health, it said that the dexmedetomidine hydrochloride injection had US sales of about $156.2 million in the 12 months to June 30, 2014. n

Hospira challenges FDA’s ‘unlawful’ approval of Precedex generics

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WASHINGTON DC, US

The US Court of Appeals for the Federal Circuit has affirmed a lower court’s ruling that an Apotex patent covering a method of making a drug is unenforceable due to inequitable conduct by the company’s founder and chairman Bernard Sherman.

Apotex, Canada’s largest manufacturer of

generic drugs, appealed against the decision from the US District Court for the Southern District of Florida.

In its ruling on August 15, the Federal Circuit agreed with the district court, finding that it did not “abuse its discretion in finding inequitable conduct”.

The patent at suit, 6,767,556, covers a process

Federal Circuit strikes down Apotex patent for ‘inequitable conduct’

label that “carves out” the patented method of use from the brand drug’s labelling, it said.

“The FDA’s role is ministerial only and it may only approve such a carve-out where there is no overlap between the brand’s description of the method of use protected by the patent … and the indications remaining in the generic’s proposed labelling,” it added.

It said that the court must take immediate intervention to avoid irreparable harm to the company, adding that the “market will be flooded immediately with generic version of Precedex”,

for manufacturing moexipril tablets, which are used to treat hypertension and congestive heart failure. Sherman wrote the patent application and is listed as its main inventor.

Apotex sued drug company UCB in 2012, accusing it of infringing the ’556 patent by manufacturing and selling its moexipril products Univasc and Uniretic.

The appeals court found, however, that these products were made in accordance with a method listed in another patent that UCB licenses from Warner-Lambert.

“Specifically, the district court found that Dr Sherman was aware that Univasc was made according to his claimed process, concealed this knowledge from the USPTO, and misrepresented the nature of Univasc and the prior art through his counsel’s arguments,” it said in the appeals court’s decision.

The district court also found that Sherman had withheld prior art and submitted results of experiments that he had not conducted to support his patent application.

The appeals court approved the district court’s ruling in favour of UCB. According to Forbes, Sherman has a net worth of $3.9 billion. n



News25


LsIPR Newsletter 02:14

HOW TO FORTIFY YOUR INNOVATIONS, IDEAS AND TRADEMARKS

Innovations, models and trademarks are a valuable asset in any business. They enhance a company’s

distinguishing capacity, boost its impact, strengthen its competitive position and make it more attractive to

investors. Therefore, there is every reason to give Intellectual Property a prominent place in your business

strategy. We can support you by protecting and enriching your innovations, models and trademarks,

thanks to our extensive range of services and the expertise of our trademark, design and patent specialists

who find solutions where others don’t. We are the largest consultancy in Intellectual Property in the

Netherlands and one of the most pioneering firms in Europe. If you would like to know more, visit www.nlo.nl

MARYLAND, US

The FDA has accepted applications by generic drug makers Mylan and Novartis subsidiary Sandoz for a three-times-weekly version of blockbuster drug Copaxone (glatiramer acetate), it was announced on September 2.

Sandoz intends to develop and commercialise the Copaxone three-times-weekly generic with Massachusetts-based Momenta Pharmaceuticals, whose chief executive and president Craig Wheeler said yesterday: “We are pleased to announce the acceptance of the ANDA for our three-times-a-week generic Copaxone for review.”

Teva has been pulling out all the stops in preparation for the expiry of its US patent covering the original once-daily formulation of the multiple sclerosis drug in May. The launch of the three-times-weekly formulation

in January was its last ditch attempt at retaining its share in the market.

In July, Teva reported that more than half of all Copaxone prescriptions in the US were for its new three-times-weekly formulation.

In August, Teva received a notice that Indian pharmaceutical company Dr. Reddy’s intended to make a generic version of the three-times-weekly formulation of Copaxone, which is protected by two patents due to expire in 2030.

In a statement Teva said that it will continue to vigorously defend its IP rights whenever they are challenged, and that it intended to file a lawsuit against Dr. Reddy’s within the 45 day period provided under the Hatch-Waxman Act.

In the six months up to June 30 this year, Copaxone generated sales of $2 billion, down 6% on the same period last year. n

FDA accepts generic applications for three-times-weekly Copaxone

Scottish independence questions for life sciencesThe UK’s first minister for life sciences, George Freeman, has warned that a yes vote in the forthcoming Scottish independence referendum will damage its life sciences research industry.

According to The Independent newspaper, Freeman said, on a visit to research facilities across Scotland: “Scottish science and innovation makes a vital contribution to the UK’s world-class research base, bringing benefits for business and society as a whole.

“However, our position has been made very clear to date on this important issue: if Scotland left the UK, the current framework for research could not continue.”

INBRIEF



NEW JERSEY, US

Novartis’s generic arm Sandoz may not market a generic version of Maryland-based United Therapeutics’ Remodulin (treprostinil) hypertension drug, the US District Court for the District of New Jersey ruled on August 29.

Judge Peter Sheridan said that the 6,765,117 patent, which covers a process for preparing certain compounds, is both valid and

enforceable, and that Sandoz may not make a generic version of Remodulin until the patent expires in October 2017.

He also upheld United’s 7,999,007 patent, another patent that covers Remodulin and is due to expire in 2029, but found that Sandoz’s proposed generic product would not infringe it.

Reuters reported that Sheridan found Sandoz did not prove sufficiently that the ’117 patent was invalid, and added that it was more likely

Sandoz barred from making Remodulin generic until 2017

WASHINGTON DC, US

The Pharmaceutical Research and Manufacturers of America (PhRMA) has voiced concerns about the FDA’s draft guidance on biosimilars, which if enacted, it suggests, could have an impact on the safety of biosimilar products.

In May, the FDA released Clinical Pharmacology Data to Support a Demonstration of Biosimilarity to a Reference Product, which was intended to help drug makers design their clinical pharmacology studies, which demonstrate how similar a biological product is to its reference product.

It created four categories to help quantify the similarity of two biological products that can be used to determine whether further clinical studies need to be undertaken. The categories are “not similar”, “similar”, “highly similar”, and

“highly similar with fingerprint-like similarity”.

In its letter dated August 12, PhRMA called this hierarchy “beyond the scope of the draft guidance”, and said that the relationship between the two latter categories is unclear. It suggested that the FDA remove the four-tiered framework and, if it does not, it should “substantially revise” it, as it finds the definitions of the four categories to be “vague and confusing”.

“In particular, PhRMA suggests that FDA clarify the meaning of the new ‘similar’ category, which could be interpreted by some as being inconsistent with the Biologic Price Competition and Innovation Act’s (BPCIA’s) requirement,” it said in the letter.

PhRMA also asks the FDA to clarify when it believes clinical pharmacology data is “sufficient to demonstrate that a proposed

PhRMA reacts to FDA’s biosimilars guidance

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biosimilar has no clinically meaningful differences in safety, purity, and potency from the reference product,” as well as the content on safety and immunogenicity studies.

In the guidance, the FDA said that safety and immunogenicity data derived from clinical pharmacology studies may need to be supplemented by additional evaluations, either before or after the product has been approved, but PhRMA says that, in order to protect patient safety, a premarket evaluation of safety and immunogenicity is “essential”.

“The FDA’s standards for accepting clinical pharmacology data can have serious implications for patient safety, as well as the purity and potency of biosimilar products,” PhRMA said.

“PhRMA hopes that FDA will continue to seek stakeholder input openly and transparently as it implements the BPCIA.” n

than not that generic sales by Sandoz would infringe the patent.

United Therapeutics’ chief executive Martine Rothblatt said: “We are pleased with the court’s ruling today confirming the validity and enforceability of the ’117 patent.

“We have always emphasised our investment in scientific advances and the resulting intellectual property that allows us to bring our products to patients, and this decision is a validation of that emphasis.”

United Therapeutics said that it is analysing the court opinion and assessing its steps with respect to the ’007 patent, which may include an appeal to the US Court of Appeals for the Federal Circuit.

Remodulin is an injection used to treat pulmonary arterial hypertension. In the six months to June 30, it generated net sales of $605 million.

Sandoz filed for an ANDA with the FDA for approval to make and sell a generic version of Remodulin in 2011. In the same year it filed for summary judgment from the court that the ’117 patent was invalid, arguing that it had allegedly been previously disclosed in another patent application that was filed in 1985. n



DELAWARE, US

Actavis-owned pharmaceutical company Forest, along with US-based Adamas Pharmaceuticals, has sued Indian generic drug maker Lupin for infringing seven patents directed to its Alzheimer’s drug Namenda XR (memantine hydrochloride), a once daily version of Namenda.

Forest, which markets the drug in the US, holds one of the patents at suit. US patent 8,039,009 covers pharmaceutical compositions of Namenda’s active ingredient and is due to expire in 2029. Adamas Pharmaceuticals holds the remaining six patents, which cover methods for administering the drug.

The companies filed the case at the US District Court for the District of Delaware on Friday (August 15), in response to an Abbreviated New Drug Application (ANDA) submitted by Lupin.

In July, Lupin sent the ANDA to the US Food and Drug Administration for approval to make and sell memantine capsules in 7mg, 14mg, 21mg and 28mg strengths before the Namenda patents expire.

In its application, Lupin argued that claims in the seven patents are invalid, unenforceable, or will not be infringed by its generic products.

Forest said in its complaint that Lupin’s filing of the ANDA constitutes infringement of the six Adamas patents, although it does not allege that the ‘009 is infringed.

“To the extent that discovery in this action demonstrates that assertion of the ‘009 patent against the Lupin generic products is warranted, plaintiffs reserve the right to assert it,” Forest said in the complaint.

Forest also claimed Par Pharmaceuticals infringed the patents by filing an ANDA for approval to make and sell 28mg capsules of memantine.

It has asked for judgment that the companies have infringed the patents, and for monetary relief.

In February, Forest announced that it would discontinue Namenda to focus on its once daily version of the drug, Namenda XR, effective August 15. n

Forest sues Lupin to protect $1.5bn Namenda

Novartis sues Zydus over Alzheimer and Parkinson’s disease drugNovartis Pharmaceuticals has launched a lawsuit against generics company Zydus Noveltech and its subsidiaries, accusing them of infringing patents relating to the drug rivastigmine used to treat Alzheimer’s and Parkinson’s disease.

In a lawsuit filed at the US District Court for the District of Delaware, Switzerland-based Novartis accused Zydus and its subsidiaries Zydus Pharmaceuticals and Cadila Healthcare of infringing two of its patents.

Novartis said an ANDA submitted by Zydus to the FDA would infringe its US patents 6,316,023 and 6,335,031.

INBRIEF

LSIPR Newsletter 08:1414 IP STRATEGY: PLURISTEM


15LSIPR Newsletter 08:14 IP STRATEGY: PLURISTEM

Several years after scientists found a way to harvest stem cells efficiently from the placenta after birth, companies are turning to it increasingly as a source for

cell-based therapies.

The organ that for nine months keeps both mother and baby healthy during pregnancy and which, further research suggests, also plays a role in their long-term health, is a rich source of stem cells.

However, so understudied is the placenta that the Maryland-based Eunice Kennedy Shriver National Institute of Child Health and Human Development (NIH) has announced a Human Placenta Project, an initiative aimed at “unlocking the secrets” of the one-pound (500g) organ.

The NIH hopes that the project will create a greater understanding of the placenta’s structure, development and function. Meanwhile, one company in Israel is using the placenta’s potential to develop novel therapies for the treatment of cardiovascular diseases and pre-eclampsia.

Pluristem Therapeuticas extracts cells from donated placentas and cultures them using a proprietary technology to create its patented PLX, or ‘placental expanded’ cells, a drug delivery platform that releases therapeutic proteins in response to different inflammatory diseases.

As Zami Aberman, chairman and chief executive of Pluristem, explains, placental cells’ unique position as an intermediary between mother and baby means they’re less likely to be rejected by the body after administration.

“In nature, the placenta is a place where the mother and the baby are communicating,” he says. “Even though they have separate immunological systems, they are not attacking each other.”

Aberman continues: “PLX cells have been injected into patients in clinical studies two weeks apart, or three months apart, from the same donor, without an immune reaction, which cannot be achieved by other cells.”

Pluristem cultures its cells using a 3D scaffold, as opposed to plastic 2D plates, which can make the cells behave a certain way. “When they reach confluence on a 2D plate they send signals to stop growing,” Aberman says.

“We’re generating a 3D micro-environment for the cells that is completely different from the 2D,” Aberman explains.

“To the cells it’s a human-like micro-environment.”

15

Pluristem develops therapies using cells from the placenta that have been cultured in a

unique way. LSIPR finds out how the company protects and nourishes its technologies.

Great expectations

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IP STRATEGY: PLURISTEM LSIPR Newsletter 08:14

He continues: “The 3D cell-to-cell communication and the controlled culture environment in the bio-reactor enable us to achieve different gene expressions that allow us to generate the required secretion profiles for specific therapeutics.”

What Pluristem gets are off-the-shelf cells that can help heal damaged tissue, such as muscle, help tendon injuries and repair rotator cuffs.

ConceptionPluristem acquired the basic IP on the 3D culturing technology from the Weizmann Institute of Science and the Technion–Israel Institute of Technology in 2007.

Aberman explains that Pluristem had discovered a few years before then the importance of culturing conditions in cell therapy.

“Tiny changes in the culturing process, such as the pH levels, can generate an epigenetic change in the cell. That led us to the decision that we had to develop a manufacturing tool that would allow us to do the manufacturing in precisely the same condition every time.”

From its initial IP, the company developed a variety of technologies to control the manufacturing so that it would yield the same cells every time, and found ways of changing cell properties by altering the culture conditions, creating opportunities for creating new IP.

ProtectionThere are four levels of IP protection, Aberman explains. “The first level of protection is the 3D culturing. As a result of the 3D culturing, the cultured cells are different from cells grown on

a 2D plate, generating a unique composition of cells.

“Our innovation is to take cells from nature and grow them on the 3D scaffold, which generates a change in the cell that can be analysed in the gene profile expression.

“We generated a unique, proprietary composition of matter due to the 3D scaffold, which is the second layer of protection.”

The third layer is the therapeutic use of the cells, and the final layer is the equipment Pluristem developed to manufacture the cells.

“You have different levels of protection and you apply them as needed based on the infringement of the patent,” Aberman says.

Pluristem currently holds 30 patents, many of which cover cultured placental cells and the methods for culturing them, which have been issued by the US, EU, and countries including China, Russia and South Africa. It has 120 applications pending.

Aberman says that the company’s strategy is to start filing in the US, then make a decision as to where else to file based on the therapy’s target.

“Usually we’ll file our patents in the US, Europe, Japan, Korea and Australia, and sometimes in Russia, South Africa and South America—it depends,” he says.

Pluristem also has a number of trade secrets, mainly to protect the manufacturing processes. Patents protect the definition of 3D culturing, and the general culturing condition, but the processes that provide greater stability in the

cultured cells are protected by trade secrets, Aberman explains.

The field is ripe for creating new IP, too. “Every year we file two to six new patent families, so it’s growing all the time,” he says.

At the moment, Pluristem is working with the Charité university hospital in Berlin to develop new products, and has licensing agreements with a range of different companies that develop Pluristem products for specific indications.

“When we start developing the project, the cells are perfected by our 3D culturing,” says Aberman.

“For example, our first partner was United Therapeutics. We out-license them the marketing rights to the cells for pulmonary hypertension, while we keep the IP and the manufacturing rights, which isn’t common in this area,” Aberman says.

So far, Pluristem does not have any approved products, but it is currently conducting Phase II clinical trials for critical limb ischaemia (the sudden loss of blood flow to a limb), intermittent claudication, and muscle injury.

One of its product lines, focused on the area of pulmonary hypertension, is licensed to United Therapeutics Corporation, based in Maryland.

Long termPluristem’s goal is to receive a biologic licence application for one of its products.

“We assume our first approved product will be for an indication of severe pre-eclampsia or bone marrow transplant failures,” he says.

He says that Pluristem hopes to take advantage of the adaptive licensing provision in Europe, and the breakthrough therapy designation in the US, which allow drug makers to enter the market with their much-needed therapies faster.

“That’s very important to us as a public company,” Aberman says.

His aim is to “tune” the cells so they can be used for specific indications, as is being done with antibodies. “Just as there are antibodies for specific indications, we will have cell types for specific indications and specific fields.

“By using the 3D technology we can tune the cells’ secretion properties, and ten years down the road the world will understand that the source of the cells is important, but the culturing is more so, and we’ll have many products on the market.”

With the NIH’s efforts to promote understanding of the placenta, we could be on the brink of a new era of discovery. n

“From its initial IP, the company developed a variety of technologies to control the manufacturing so that it would yield the same cells every time.”

Client: Birch, Stewart, Kolasch & Birch, LLP (BSKB) ContaCt: Elizabeth Richards, [email protected], 703.205.8000

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18 LSIPR Newsletter 08:14


LEGAL UPDATE: MYRIAD/MAYO

Anyone who attended the 2014 BIO International Convention in San Diego in June was left in no doubt about which subject

is dominating discussion among IP lawyers working in the life sciences: the patent eligibility of natural products in the US following the Myriad and Mayo cases.

The US Patent and Trademark Office (USPTO) was therefore probably unsurprised when its request for comment on the guidelines it issued following those court decisions prompted an avalanche of replies. It may have been more surprised by how negative many were.

For those unfamiliar with this particular controversy, it begins with Section 101 of Title 35 of the US Code, the title covering patent law. The section states that: “Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.”

However, the law relating to subject matter eligibility is changing fast because of a number of recent court decisions, including Association for Molecular Pathology v Myriad Genetics, Inc (Myriad) and Mayo Collaborative Services v Prometheus Laboratories, Inc (Mayo).

To keep up with these changes Andrew Hirshfeld, the USPTO’s deputy commissioner for patent examination policy, issued a guidance memorandum in March this year titled Guidance For Determining Subject Matter Eligibility Of Claims Reciting Or Involving Laws of Nature, Natural Phenomena, & Natural Products and designed to implement a new procedure to address the changes in the law relating to subject matter eligibility.

The USPTO then asked members of the public to submit their written comments on the guidance by July 31. “The office would like for members of the public who believe that the Supreme Court decisions could be implemented in an alternative manner from the approach taken in the guidance to submit written comments presenting their alternative approach and the legal rationale for the alternative,” it said.

“The public is also invited to suggest additional examples for use by the Office to create a more complete picture of the impact of Supreme Court precedent on subject matter eligibility, and to provide comments on the subject matter eligibility of particular claims, including the

Sifting through the published comments on the USPTO’s Myriad/Mayo guidelines, LSIPR found them to be overwhelmingly negative.

sample claims discussed at the 2014 BIO International Convention,” it added.

Professional viewsThere was no shortage of responses. IP organisations and other associations, academic and research institutions, law firms, companies and individuals all weighed in with their comments.

Of these, the one that has received most publicity has been from a group of 12 national and regional biotechnology industry associations including the UK BioIndustry Association, BIO Deutschland, EuropaBio and the Japan Bioindustry Association.

As LSIPR reported, after its response was submitted, the group suggested that establishing the guidelines will stymie innovation by acting as a disincentive for investment in biotechnology research and development.

“Internationally harmonised, science-based regulatory and legal frameworks are important for competitiveness and innovation to ensure faster and more equitable access to new biotech products and processes for patients, farmers and consumers around the world,” the group said.

By contrast, the USPTO’S guidance will be a “significant departure from internationally accepted norms of patentability”, particularly

with regard to industrial, agricultural, and pharmaceutical preparations of naturally-derived substances, compositions and processes.

“Inventive preparations based on naturally-occurring substances have historically been of great importance in biotechnology, and innovation in this area has been spurred, at least in part, by the availability of patent protection,” the group said.

“By singling out naturally-derived biotechnology inventions for special, disfavoured treatment, the guidance would establish peculiar disincentives for investment in research and development of entire categories of biotechnology,” it added.

According to the submission, the group’s member companies have already received rejections from the USPTO for patents directed at pharmaceutical formulations having purified naturally-occurring substances as active ingredients, diagnostic laboratory procedures, and other inventions that were neither considered nor discussed in the US Supreme Court’s Myriad and Mayo decisions.

“Such rejections under the new guidance, if they were to become systemic, would seriously impair investment incentives in new, socially beneficial technologies,” the group said.

Other submissions were equally forthright.

A hostile response to the USPTO’s guidelines

LSIPR Newsletter 08:14 19


LEGAL UPDATE: MYRIAD/MAYO 19


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on Governmental Relations, the Association of American Universities and the Association of Public and Land‐Grant Universities.

“We are deeply concerned about the USPTO guidance memorandum and its unwarranted, as well as legally inconsistent, broad changes in examination practice,” their letter said.

“The ability of our members to bring the benefits of research to the public is significantly decreased if patents on valuable and meritorious university technology cannot be obtained. Secure and predictable protection is a prerequisite for our licensees to justify substantial investments in commercialising university discoveries.

“The guidance adversely and unnecessarily impacts our ability not only to license and commercialise future discoveries and inventions, but also the validity of many existing patents for products, particularly in life science areas which make up the majority of university patents,” it added.

Six law firms and around 40 individuals added their voices too, and again there was broad agreement. As an example, the Washington DC-based Sutherland Asbill & Brennan LLP added to the criticism.

“Joining in the apparent consensus of most IP experts in this practice area, it is our firm belief that the USPTO’s guidelines are based on an incorrect and overly broad interpretation of what no longer may be deemed patent-eligible subject matter based on relevant Supreme Court decisions discussed herein,” said its submission.

“In the words of the Mayo court: ‘This court has repeatedly emphasised a concern that law not inhibit future discovery by improperly tying up the use of laws of nature and the like. Rewarding with patents those who discover laws of nature might encourage their discovery’,” added the letter, which was signed by Sutherland associate Jana Nelson.

“In addition to the guidance being based on a fundamentally flawed analytical framework, it directly conflicts with the USPTO’s constitutional mandate to promote science and the useful arts. Notably, by restricting the scope of patent-eligible subject matter the guidance threatens to effectively suppress innovation in industries relating to biotechnology and biopharmaceuticals,” it added.

The USPTO has said it will issue an update to the guidance “once it has carefully considered all feedback and the developing law regarding subject matter eligibility”. n

35 USC §101 that adheres to established case law and does not impermissibly expand the judicial exceptions to patent-eligible subject matter under 35 USC §101,” concluded the letter, which was signed by Charles Kinzig, GSK’s vice president, patent litigation and IP policy, North and South America.

Switzerland-based pharmaceuticals company Novartis was equally hard-hitting. It shares the view of the many other stakeholders who have submitted comments that the USPTO has misinterpreted the explicitly narrow holdings of the Myriad and Mayo cases, applying them to a far broader range of subject matter than was ever intended, and overstepping the bounds of the role with which the office has been entrusted.

“However well-intentioned, the result of this guidance is the creation of new substantive law that neither Congress nor the courts have endorsed, that creates undue burdens on patent applicants operating in the biopharmaceutical field, and which has already left a trail of confusion and uncertainty that, if not corrected, will take years for the courts to sort out,” Novartis said.

“On all counts, the loser is innovation and its expansive array of beneficiaries, including patients who, like us, depend on the strong incentives that patents provide to ensure a robust future of medicine.”

The conclusion of the submission, signed by Corey Salsberg, senior legal counsel, IP litigation and policy, at Novartis International AG, was that subject matter eligibility cuts to the very heart of the patent system and that law-making in this area has a profound impact on the scope and direction of innovation.

“Such an undertaking should be left to Congress and the courts, whom the public has entrusted with this role, and in all events cannot be taken lightly,” said Novartis. “We believe it only proper for the office to withdraw its inconsistent guidance, and to issue new guidance only after careful reflection and due consideration of the points raised above and in other stakeholders’ comments.

“Should the office maintain its present approach, we at least request that it duly and carefully consider our and others’ suggested revisions,” it added.

Blunt responsesAway from the corporate sector, there were similarly forthright submissions from academic and research institutions, including one from four relevant US bodies: the Association of University Technology Managers, the Council

“Subject matter eligibility cuts to the very heart of the patent system and law- making in this area has a profound impact on the scope and direction of innovation.”

UK-based pharmaceuticals company GlaxoSmithKline (GSK), in its letter, said that “Denying patent protection to naturally occurring compounds … will disincentivise research on natural products, adversely impact the development of new medicines, and negatively impact global health.”

The guidance is not supported by case law, improperly extends the holdings of Myriad and Mayo, its factor-weighing test breaks from former USPTO guidance and it effectively creates a new legal standard, said the company.

“GSK requests that the office issue new guidance regarding patent-eligible subject matter under

20


EXPERT COMMENT: PERSONALISED MEDICINE LSIPR Newsletter 08:14

The field of personalised medicine is diverse, and a dialogue with interested technology, patent and business

experts needs to begin.

The US Food and Drug Administration’s Center for Drug Evaluation and Research has defined personalised medicine as “... using genetic or other biomarker information to make treatment decisions about patients”. The European Commission uses the term personalised medicine to refer to “a medical model using molecular profiling for tailoring the right therapeutic strategy for the right person at the right time, and/or to determine the predisposition to disease and/or to deliver timely and targeted prevention”.

Using either definition, personalised medicine includes a broad range of processes and technologies, across aspects of diagnostics, data analysis, treatments, treatment monitoring and related areas. We have summarised selected personalised medicine areas and indicated some interrelationships between these areas in Figure 1. These areas feature the application of both pre-existing technologies and emerging innovations, all of which can be the subject of patent applications.

Partnerships in personalised medicinePartnerships can be pivotal to securing value in personalised medicine, as might be expected in a technologically intense area where very diverse capabilities may be required to deliver effective solutions.

Drivers for partnerships in personalised medicine include:

• Capability gaps: personalised medicine players may lack internal capabilities spanning relevant technology and business requirements;

• Cost: capabilities can be costly to develop and maintain, making outsourcing certain capabilities a cost-effective option for even the largest of players; and

• Emerging ‘value chains’: new technologies open new opportunities to securing value (eg, new targets, more complex targets, optimised dosages), possibly increasing the complexity of commercialisation options.

Personalised medicine patent activityClear reference points and boundaries are essential to informing assessments of relative positions within an ‘IP Landscape’, a report that provides a snapshot of the patent situation of a specific technology. Defining personalised medicine and developing the axes on which to plot and interpret the vast amounts of data available are vital for useful IP Landscape mapping. For those who can draw an informative patent map and work out a good navigational route through complexity, there is an opportunity to gain significant competitive advantages.

To draw an analogy from Lewis Carroll’s The Hunting of the Snark, without boundaries, maps become meaningless plains which, while they may provide comfort, do not really improve understanding.

He had bought a large map representing the sea,

Mapping the IPLandscape

For those who can draw an informative patent map and work out a good navigational route through the complexities, there is an opportunity to gain significant competitive advantages through making the right partnerships, argue Quentin Tannock and Anna Duch.

Without the least vestige of land:

And the crew were much pleased when they found it to be

A map they could all understand.

CambridgeIP conducted a snapshot of the IP Landscape of personalised medicine in May 2014. The snapshot is not comprehensive and serves to simply illustrate high-level trends and to identify most active players and commercial focus areas. It is important to note that many relevant technologies enabling personalised medicine solutions predate the emergence of ‘personalised medicine’ as well-known terminology.

Figure 2 illustrates patent family filing trends from our personalised medicine IP Landscape snapshot.

There are around 12,000 patents and patent applications in our IP Landscape snapshot, in more than 6,000 patent families—indicating a dynamic area, with a relatively high proportion of individual innovations given

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LSIPR Newsletter 08:14 EXPERT COMMENT: PERSONALISED MEDICINE

the overall age of the area (as patent families can be considered as proxies for individual inventions).

As Figure 2 illustrates, there has been an appreciable increase in personalised medicine patent activity from around 2001 onwards. Patent activity in the area appears to have levelled from around 2006 at a relatively high level, possibly indicating sustained commercial interest in the overall area. Top patent owners (or assignees) in personalised medicine form a vibrant mix of pharmaceutical corporations and academic institutions.

Using comparative techniques, readers of IP Landscape maps can build up a detailed understanding of industry structures, trends

in commercial research and development (R&D) interests, the relationships between technology components and relationships between entities active in the relevant areas.

Fact-based investment, business, IP and R&D strategies are enabled even in highly complex technology-market spaces. For the purposes of our IP Landscape snapshot we broadly divided personalised medicine patents into three high level areas: diagnostics, therapy and data processing using International Patent Classification (IPC) codes as quick proxies for the three areas (Figure 3).

Figure 3 illustrates patent activity trends over time in the three areas we defined for this IP Landscape snapshot.

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“Using comparative techniques, readers of IP Landscape maps can build up a detailed understanding of industry structures, and trends in commercial research and development interests.”

©2014 Cambridge Intellectual Property Ltd. All rights reserved

Figure 1: Aspects of personalised medicine

In-labelleddrugs

Companiondiagnostics

Biomarkerapproach Approach

Imaging

Patient selection

Therapeuticarea

Drugs

Small molecules

Peptides

Other

Central NervousSystem (CNS)

Neurodegenerativedisease

Osteoarthristis

Inflamation

Diabetes

Arteriosclerosis Ischemia

Oncology/cancer

Proteins

Aptamers

Aptamers

Antibodies

Antibody fragments

Diagnostics

Patient data analysis

Personalisedmedicine

Personalised therapy

Therapy monitoring

Therapymonitoring

Monitoring

Dosing

Safety

Efficacy

Molecular profile

GenomicsPatient profile


Figure 2: Personalised medicine patent families over time

Number of patents by filing year: Annual and cumulative

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Number of new applicants Cumulative

22 LSIPR Newsletter 08:14


EXPERT COMMENT: PERSONALISED MEDICINE

• Diagnostics accounts for most new patent activity in the area—perhaps reflecting the pre-existence of much therapy-related IP; and

• Data processing is a theme that appears to be increasing steadily in importance since around 2000—one driver is improvements in sequencing technologies, which drive up data availability.

Case study: Myriad GeneticsMyriad Genetics, Inc is a US-based molecular diagnostics company, perhaps best known for its heriditary breast and ovarian cancer testing involving the BRCA1 and BRCA2 genes. Myriad Genetics also offers predictive tests for other cancers, including colorectal, uterine and pancreatic cancers.

Myriad Genetics’ patent portfolio includes patents from the early 1990s to the present day. Figure 4 summarises Myriad Genetics’ patent activity over time. Spikes in patent activity in 2001, 2002 and 2007 are followed by what appears to be a decline in patent activity (even after accounting for a lag in the publication of patent applications).

Consideration of the Myriad Genetics’ patent portfolio enables us to identify several phases in the Myriad Genetics IP strategy, illustrated in Figure 5. These phases are:

• A national phase, with mainly US patent filings and a ‘traditional’ patent-enforcement strategy;

• An international roll-out phase, where the national patents and enforcement strategy are rolled out around the world and the company begins to make some patent acquisitions; and

• A trade secret phase, where in more recent years Myriad Genetics begins to rely more heavily on trade secret protection—especially around ‘variants of known significance’ (VUS) data; and as older Myriad Genetics patents approach their expiry dates.

ConclusionsCo-dependences and strategic or practical reasons for relying on externally developed technologies may impact partnering and IP strategies in personalised medicine partnerships. Such co-dependencies and requirements for reliance on external parties’ developments in personalised medicine are often the result of the


Figure 3: Diagnostics, therapy and data processing trends within the personalised medicine IP Landscape snapshot

IPC Time Trend

IPC DESCRIPTION TECHNOLOGY AREA

C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES OR MICRO-ORGANISMS

DIAGNOSTICS

G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES

A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES

THERAPY

A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

G06F ELECTRIC DIGITAL DATA PROCESSING DATA PROCESSING

Patent applications may be unpublished for 18+ months. Therefore the number of reported patents for the last 2 years may be under-represented. It may take several years for a patent to be granted. Therefore the number of granted patents may be under-represented for the last few years.

.

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A61KC12Q A61PG01N G06F

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Figure 4: Myriad Genetics’ patent families over time

Number of patents by filing year: Annual and cumulative

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LSIPR Newsletter 08:14 23


EXPERT COMMENT: PERSONALISED MEDICINE

capability gaps mentioned above. To provide a simple example, a drug company may depend on a companion diagnostic for launch of the drug, while a diagnostics company depends on the drug’s success to sell the companion diagnostic to that drug.

In such cases, the focus of partners can dictate the value the partners place on particular components of a personalised medicine solution, and consequently the component-related IP they seek to own or control. For example, IP relating to diagnostics platforms will probably be of most interest to a diagnostics development company, whereas IP relating to drug products will probably be of most interest to a drug development company. This, coupled with co-dependencies, can lead to relatively balanced negotiating power between potential partners.

To continue with the simple example above, a companion diagnostic is of less value if it cannot be deployed in a drug’s key geographical market. As in other areas, personalised medicine IP-related partner selection criteria can include a Freedom to Operate (FTO)


Figure 5: Myriad Genetics patent strategy phases

Number of patent filings: Stacked Applications / Granted (based on filing year)

National patent strategy phase

(Mainly USA patents and enforcements)

International patent strategy phase

(International roll-out: increased international applications, enforcements, patent acqusitions)

Trade secrets phase

(Accumulation of private ‘variants of known significance’ (VUS) data)

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1

Quentin Tannock, LLB (Hons), LLM (Cantab), has significant IP Landscape, IP strategy and investment strategy experience. His IP-related analysis has been covered in a variety of media. He has written articles in leading international commercial law journals, has contributed chapters to textbooks on IP strategy, IP policy and commercialising early stage technologies, and presents regularly at international conferences. He has prior experience in corporate strategy, M&A and IP advisory work for blue chip companies and a nanotechnology venture capital investment group; and facilitated corporate R&D collaborations in nanotechnology and electronics at Cambridge University. He is a member of the Lambert Working Group on IP tasked by the UK government to draft model contracts for industry-university collaborations.

Anna Duch, PhD (Cantab), leads delivery of IP Landscape and IP strategy projects in health and life sciences and manages production resources for CambridgeIP. She holds a PhD in biological science from the University of Cambridge. Her areas of expertise include personalised medicine, gene therapy, medical technology and molecular diagnostics. She is regularly commissioned by international organisations such as WIPO, EPO and the European Commission to conduct research and disseminate information in the areas of health and medicine to promote research and improve universal access to healthcare. Prior to joining CambridgeIP Duch gained research experience in molecular and cell biology, and embryology in Medical Research Council and Wellcome Trust institutes, and research institutes in Poland and the US.

interesting to observe trends in this and other aspects of the personalised medicine IP Landscape over the next several years. n

Quentin Tannock is the executive chairman of CambridgeIP, a research and analysis consultancy focusing on innovation and IP. He can be contacted at: [email protected]

Anna Duch is a senior associate at CambridgeIP. She can be contacted at: [email protected]

assessment of whether you and your potential partner have FTO around key developments and in key geographical markets.

Thorough IP Landscape research is often required to help identify and rank partners, as well as to inform negotiating positions and fact-based future IP strategies. As ever, do not forget to consider what happens if your partnership fails. Partnerships can end unexpectedly, and for unexpected reasons. Think through the implications of failture from the IP perspective. For example, who will own the IP created? And how will past and future IP-related costs be distributed?

The growing importance of data and of related technologies for storing, searching and analysing data in many personalised medicine solutions is interesting and may impact partnering and IP strategies. As more information is gathered in relation to individuals and their responses to treatments and other factors, data grow in size, becoming more detailed and more valuable.

Data and data protection appear to be an increasingly important aspect of the Myriad Genetics IP strategy, for example. It will be

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