Evergreening or extension of drug life through various product life cycle management tactics is an issue that significantly affects the generic pharmaceutical sector. Evergreening results in delayed market access for generic companies as well as higher drug prices in market for a longer duration. Both of these results are detrimental to patients. This article looks at evergreening practices seen in various countries across the develop ment index. It covers diverse countries on the development spectrum, ranging from countries like Canada and Australia to countries like India, Philippines and Thailand. It highlights the response that Governments and generic companies are taking to regulate and to counter ever-greening practices. The types of evergreening practices noted are follow-on or secondary patents, aggressive litigation practices, and finally patent mechanisms being linked with regulatory approval (linkage) introduced via Free Trade Agreements.
FaunceT. A.LexchinJ. (2007) ‘Linkage’ pharmaceutical ever greening in Canada and Australia (June 1, 2007). Australia and New Zealand Journal of Health Policy1 (4): 8, June 2007, http://ssrn.com/abstract=1405010, accessed 11 February.
Pfizer's blockbuster product — Atorvastatin Calcium (Lipitor®) — has a plethora of patents on various crystalline forms, including one patent for crystalline Forms I, IV listed on the Orange Book.
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For, for example, Desloratadine (Clarinex®) from Loratadine (Claritin ®).
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For, for example Eszopiclone (Lunesta®) from Zopiclone (Imovane ®).
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Abbott's Fenofibrate (Tricor®) capsules were earlier sold in 54 mg and 160 mg; and this was later changed to 54 mg and 160 mg tablets (Tricor®), and which was again changed to 48 mg and 145 mg.
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For, for example, Venlafaxine immediate release tablets (Effexor®) to an extended release version (Effexor XR®).
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For instance, US patent 6,333,198 for substantially pure Lamotrigine.
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For instance, US patent 6,469,012 for use of Sildenafil Citrate in erectile dysfunction.
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US patent 6, 419,958, covering therapeutic blood plasma concentration of venlafaxine over a 24h period.
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For instance, US patent 6, 455,574 covers use of Atorvastatin and Amlodipine, marketed as Caduet®.
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US patent 6,784,177 marketed as BiDil®.
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Astra switched from racemic Omeprazole (Prilosec®) to Esomeprazole (Nexium®) which is the S-enantiomer of the racemic product, with an unprecedented advertisement blitzkrieg — ‘the Purple pill’.
For instance, GlaxoSmithkline timed the issuance and listing of multiple patents for the drug Paroxetine (Paxil®) on the Orange Book, to get four successive 30-month stays to delay the approval for a generic version. The first stay for FDA approval expired in November 2000, but the US FDA was not able to approve a generic version of Paxil until September 2003.
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For instance, the US House Judiciary Committee's Subcommittee on Courts and Competition Policy held hearings on related issues in June 2009.
The medicines in question were omeprazole, amlodipine, doxazosin, loratadine, mirtazapine and ramipril. The cost numbers come from a British Generic Manufacturers Association submission to the Health Committee of the House of Commons. Details are available in ‘The Influence of the Pharmaceutical Industry’, Fourth Report on 2004–5 session, published on 5 April 2005 (page 92). The Report is available online at http://www.publications.parliament.uk/pa/cm200405/cmselect/cmhealth/42/42.pdf, accessed 26 February 2010.
According to the US Federal Trade Commission's 2002 study titled ‘Generic Drug Entry: Prior to Patent Expiration’, generic applicants prevailed in 29 out of 40 drug product litigations (or 73 per cent). This study is available online at http://www.ftc.gov/os/2002/07/genericdrugstudy.pdf, accessed 11 February 2010.
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For instance, Abbott when faced with pre-grant opposition for its application (339/MUMNP/2006) covering heat stable formulation of Lopinavir+Ritonavir, filed not one, but two divisional applications at two different patent offices — 726/MUMNP/2009 at Mumbai Patent Office and 2474/DELNP/2009 at Delhi Patent Office — with exactly same set of claims as the parent, on the day of the opposition hearing for the parent ′339.
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Gilead lost its application: 2076/Del/1997 covering Tenofovir disoproxil in an opposition, but filed a divisional — 602/DEL/2007 with similar scope; similarly its application 896/del/2002 covering Tenofovir disoproxil fumarate was rejected, but it has 1135/DEL/2007 pending, covering similar scope.
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For instance, Glaxo abandoned its original filing for Atazanavir (805/MAS/1997) but is prosecuting core claims in a later divisional — 310/CHE/2007.
BakerB. K.Professor (2007) Standing up to Abbott's decision to withhold registration and marketing of life-saving medicines — A new variant of pharmaceutical apartheid. Health GAP, 13 March 2007. Note available online at http://www.twnside.org.sg/title2/FTAs/info.service/fta.info.service083.htm, accessed 11 February 2010.
GerhardsenT. I. S. (2006) Pfizer fights IP flexibilities in the Philippines. PHM Article, http://www.phmovement.org/en/node/186, accessed 11 February 2010.
Philippine patent No. 29,149 — same as US patent 52,73,995 and its equivalents. This enantiomer patent has been focus of litigation in various countries around the world and invalidated in Australia, Austria, the Netherlands, Norway, South Korea, Germany and the United Kingdom.
HermosaJ. A. D. (2010) Pfizer suffers setback in its campaign against generic anti-cholesterol drug. Business World, 11 February 2010, http://www.bworldonline.com/main/content.php?id=6214, accessed 11 February 2010.
IsipI. (2010) Unilab to challenge more patents to bring down prices. Malaya Business Insight, 16 February 2010, http://www.malaya.com.ph/02162010/busi5.html, accessed 17 February 2010.
Aktiebolaget Hassle v Alphapharm Pty Ltd, 212 CLR 411 2002.
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ChalmersR. (2006) Evergreen or deciduous? Australian trends in relation to the ‘evergreening’ of patents. Melbourne University Law Review30 (1), http://www.austlii.edu.au/au/journals/MULR/2006/2.html, accessed 07 May 2010.
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Article 17.10.4 of the AU US FTA.
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Arrow Pharmaceuticals Ltd v Merck & Co Inc (2004) FCA 1282.
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Apotex Ltd. (formerly GenRx Pty Ltd) v Les Laboratoires Servier (No 2) (2008) FCA 607.
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FaunceT. (2008) New forms of evergreening in Australia: Misleading advertising, enantiomers and data exclusivity: Apotex v Servier and Alphapharm v Lundbeck. Medical Law Reporter, Journal of Law Medicine16: 220.
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Alphapharm Pty Ltd v H Lundbeck A/s (2008) 76 IPR 618; (2008) FCA 559.
