[en] Today, the US leads the field of personalised medicine gene therapies, while the EU lags behind. The implementation phase of gene therapy technologies remains a significant bottleneck in Europe, with limited data on their availability, quality, safety, and efficacy. The legal framework for gene therapies differs significantly between the US and the EU as methods for the treatment of the human body by therapy are excluded from patent protection in Europe. Taking into account the creation of R&D incentives and information disclosure as core objectives of modern patent systems, this article analyses the potential to repeal the existing patentability exception to allow for patent protection for gene therapies as such. We demonstrate the contentious rationale of the exception and its inhomogeneous application and provide doubt over patent protection as a solution to the existing problems. We explore a realm that has become a neighbouring field of intellectual property law in the domain of healthcare innovation: the regulatory framework of medicinal products and regulatory exclusivities. We propose a second-tier regulatory protection mechanism, which we argue offers greater potential to address the challenges of gene therapy development in the EU healthcare market than amendments to European patent law. Specifically, we argue that granting remuneration rights for extended reporting on the administration of advanced therapy medicinal products (ATMPs) prepared under the hospital exemption might establish steering effects in the right direction.
Disciplines :
Droit économique & commercial
Auteur, co-auteur :
STIERLE, Martin ; University of Luxembourg > Faculty of Law, Economics and Finance (FDEF) > Department of Law (DL)
Valtere, Laura; UCPH - University of Copenhagen > Centre for Advanced Studies in Bioscience Innovation Law (CeBIL)
Co-auteurs externes :
yes
Langue du document :
Anglais
Titre :
Addressing the Gene Therapy Bottleneck in the EU: Patent vs. Regulatory Incentives
Date de publication/diffusion :
21 mai 2025
Titre du périodique :
Gewerblicher Rechtsschutz und Urheberrecht. Internationaler Teil
Astrid M Vicente, Wolfgang Ballensiefen and Jan-Ingvar Jönsson, ‘How Personalised Medicine Will Transform Healthcare by 2030: the ICPerMed Vision’ (2020) 18(1) J Transl Med 180. See also, Sunil Mathur and Joseph Sutton, ‘Personalized Medicine Could Transform Healthcare’ (2017) 7(1) Biomed Rep 3.
Matthew Might and Andrew B Crouse, ‘Commentary Why rare disease needs precision medicine – and precision medicine needs rare disease’ (2022) 3(2) Cell Reports Medicine, 1, 1 ff.
See European Commission, ‘Personalised Medicine’ accessed 31 December 2024.
Richard Charles Mulligan, ‘The Basic Science of Gene Therapy’ [1993] Science 926; EH Kaji and JM Leiden, ‘Gene and stem cell therapies’ (2001) 285(5) JAMA 545.
Personalized Medicine Coalition, ‘The Personalized Medicine Report. Opportunity, challenges, and the future’ (PMC, 2017) 24 accessed 31 December 2024.
Swadesh K Das and others, ‘Gene Therapies for Cancer: Strategies, Challenges and Successes’ (2015) 230(2) J Cell Physiol 259. In 2003, the first commercial gene therapy, Gendicine, was approved for the treatment of certain cancers. See Sue Pearson, Hepeng Jia and Keiko Kandachi, ‘China approves first gene therapy’ (2004) 22(1) Nature Biotechnology 3.
See World Health Organization, ‘Cancer’ accessed 31 December 2024 (reporting that cancer is the second leading cause of death globally, accounting for an estimated 9.6 million deaths, or 1 in 6 deaths, in 2018).
European Commission, ‘Personalised Medicine Conference 2016, Report’, Victoria English (ed) 7; Alliance for Regenerative Medicine and others,‘ReformoftheEUGeneralPharmaceuticalLegislation.JointPosition Paper on the Hospital Exemption Scheme for ATMPs’ (2023) 3 accessed 31 December 2024.
See Section III. below.
See Section III. below.
See Section IV.2. below.
See Section IV.1. below.
See Section VI.2. below.
Claudia Eder and Claudia Wild, ‘Technology forecast: advanced therapies in late clinical research, EMA approval or clinical application via hospital exemption’ (2019) 7 Journal of Market Access & Health Policy 1, 1.
Delphi GM Coppens and others, ‘Regulating advanced therapy medicinal products through the Hospital Exemption: an analysis of regulatory approaches in nine EU countries’ (2020) 15(8) Regen. Med. 2015, 2019.
SANCO/D5/RSR/iv(2013)ddg1.d5, ‘Regulation (EC) No. 1394/2007 on Advanced Therapy Medicinal Products. Summary of the Responses to the Public Consultation’ 3.1; Alliance for Regenerative Medicine and others (n 8) 3.
For the significant funding of drug development by the National Institutes of Health (NIH) in the US, see for example, Ekaterina Galkina Cleary and others, ‘Comparison of Research Spending on New Drug Approvals by the National Institutes of Health vs the Pharmaceutical Industry, 2010-2019’ (2023) 4(4) JAMA Health Forum 230511.
For these functions of the different legal fields, see Sections V.1. and VI.1. below.
See Section IV.1. and Section VI.2. below.
See European Commission, ‘Proposal for a Directive of the European Parliament and of the Council on the Union code relating to medicinal products for human use, and repealing Directive 2001/83/EC and Directive 2009/35/EC’ COM(2023) 192 final. See also Laura Valtere, ‘The Interface Between Patents and Regulatory Exclusivities and the View on the New EU Proposals Concerning Patent Compulsory Licensing and Regulatory Exclusivities’ [2024] GRUR International 617, 625.
See COM(2023) 192 final (n 22), Recital 18 and art 2 of the proposed Directive. The Commission addresses here data sharing obligations but not induced by legal protection. See Section VII. below.
For this discussion, see for example, Frantzeska Papadopoulou, Evergreening Patent Exclusivity in Pharmaceutical Products: Supplementary Protection Certificates, Orphan Drugs, Paediatric Extensions and ATMPs (Hart 2021) 198, 215, 231 f, 250, 255 (criticising the EU approach in adopting regulatory law without sufficient consideration of the existing IP protection system);
Daniel Gervais, ‘The Patent Option’ (2019) 20(3) N.C.J.L. & Tech. 357 (proposing an amendment to data disclosure to overcome the weakness of both systems); Valtere (n 22) 617 (addressing the interface between patents and regulatory exclusivities in light of the new EU proposals in the field of healthcare innovation).
Steven A Rosenberg and others, ‘Gene transfer into humans-immunotherapy of patients with advanced melanoma, using tumor-infiltrating lymphocytes modified by retroviral gene transduction’ (1990) 323(9) N Engl J Med; Eva Hanna and others, ‘Gene therapies development: slow progress and promising prospect’ (2016) 5(1) Journal of Market Access & Health Policy 1.
Hanna and others (n 25) 5. Its active substance is alipogene tiparvovec. It is intended to treat lipoprotein lipase deficiency, in addition. It was approved as an orphan drug. Unfortunately, the therapy is no longer authorised in the EU due to financial aspects.
Kewal K Jain, Textbook of Personalized Medicine (3rd edn, Springer 2021) 198. See also, U.S. Food and Drug Administration, ‘What is Gene Therapy?’ (25 June 2018) accessed 31 December 2024.
Viruses used in this technique are referred to as vectors. The virus is stripped of components that may cause infection or trigger an immune response in humans. Most often, adenoviruses or lentivirus are used.
Wuyuan Zhou and Xiang Wang, ‘Human gene therapy: A patent analysis’ [2021] Gene 803, 803.
European Commission, ‘Commission staff working document. Use of ‘-omics’ technologies in the development of personalised medicine’ SWD(2013) 436 final, 5; Council of the European Union, ‘Council conclusions on personalised medicine for patients’ [2015] OJ C421/03, para 8. See also Krešimir Pavelić, Sandra Kraljević Pavelić and Mirela Sedić, ‘Personalized Medicine: The Path to New Medicine’ in Nada Bodiroga-Vokobrat and others (eds), Personalized Medicine. A New Medical and Social Challenge (Springer 2016) 1, 3 f.
See Margret Ewen, ‘The Cost of Irrational Medicine Use’ (September 2011) accessed 31 December 2024 (stating that societal costs of adverse reactions were EUR 79 billion per year, according to the European Commission in 2008). See also Idar Akhmetov and others, ‘Market Access Advancements and Challenges in ‘Drug-Companion Diagnostic Test’ Co-Development in Europe’ (2015) 5 J Pers Med, 213, 214 (stating that 7% to 13% of all hospital admissions in developed European countries are caused by serious adverse drug reactions). For an economic perspective on personalised medicine for public healthcare, see Sairamesh Jakka and Michael Rossbach, ‘An economic perspective on personalized medicine’ (2013) 7(1) The HUGO Journal 1. See also Jürgen M Schneider, ‘Companion Diagnostics’ in Wolfgang Voit (ed), Transparenz/Neue Produkte. 18. Marburger Gespräche zum Pharmarecht (Nomos 2017) 295, 297.
See Hanna and others (n 25) 2; Christopher E Nelson and others, ‘In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy’ (2016) 351(6271) Science 403.
Reena Goswami and others, ‘Gene Therapy Leaves a Vicious Cycle’ (2019) 9 Frontiers in Oncology 1, 1.
See Hanna and others (n 25) 2.
The Editors, ‘Realizing DANN’s medical promise remains a costly challenge’ (2023) 616 Nature 629, 629.
See Alison Irvine, ‘Paying for CRISPR Cures: The Economics of Genetic Therapies’ (2019) accessed 31 December 2024. See also the industry surveys she refers to. For the costs of classic drug development, see the frequently cited studies: Joseph A DiMasi, Ronald W Hansen and Henry G Grabowski, ‘The price of innovation: new estimates of drug development costs’ (2003) 22 Journal of Health Economics 151 (pre-approval cost estimate of USD 802 million per drug); Christopher P Adams and Van V Brantner, ‘Estimating the cost of new drug development: is it really 802 million dollars?’ (2006) 25(2) Health Affairs 420 (estimating from around 500 million dollars to more than 2,000 million dollars, depending on therapy or developing firm); Joseph A DiMasi, Ronald W Hansen and Henry G Grabowski, ‘Innovation in the pharmaceutical industry: New estimates of R&D costs’ (2016) 47 Journal of Health Economics 20 (calculating pre-tax capitalized per approval as USD 2558 million (2013 dollars)).
Papadopoulou (n 24) 195, 220, 247, 249.
Coppens and others (n 17) 2015.
Zhou and Wang (n 29) 1, 3.
Zhou and Wang (n 29) 1, 3 (concluding that after the patient’s death in 1999 the patenting of gene therapies was rather modest until 2012 when CRISPR/Cas9 was patented and a first gene therapy in Europe was authorised).
Ricki Lewis, Human Genetics: the basics (2nd edn, Routledge 2017) 130.
European Commission, ‘Commission staff working document. Use of ‘-omics’ technologies in the development of personalised medicine’ SWD(2013) 436 final.
ibid at 6; Council of the European Union, ‘Council conclusions on personalised medicine for patients’ [2015] OJ C421/03, para 6.
Jain (n 27) 18.
Elmar Nimmesgern, Indridi Benediktsson and Irene Norstedt, ‘Personalized Medicine in Europe’ (2017) 10(2) Clin Transl Sci 61, 63.
The White House, ‘Fact Sheet: President Obama’s Precision Medicine Initiative’ (30 January 2015) accessed 31 December 2024.
George W Russell, ‘China plans leading role in ‘precision medicine’ field’ (HKU Journalism & Media, 28 February 2017) accessed 31 December 2024.
See Zhou and Wang (n 29), especially table 1 (demonstrating that the US has significantly more patents related to gene therapies) and Tim Wilsdon and others, ‘Factors affecting the location of biopharmaceutical investments and implications for European policy priorities’ (Report, CRA Project No D36423, 3 October 2022) 10 ff accessed 31 December 2024 (explaining that investment in gene therapy R&D is significantly higher in the US than in Europe). See also Alliance for Regenerative Medicine, ‘Meeting the Moment. Harnessing the Full Potential of ATMPs for European Patents’ (2022) 2 accessed 31 December 2024 (‘The number of therapeutic developers, clinical trials, and investment is stagnating in the EU-a trend in stark contrast with other regions of the world.’).
See Papadopoulou (n 24) 192 and the hospital exemption in Section IV below.
See Alliance for Regenerative Medicine and others (n 8) 3; Larry Luxner, ‘Despite Previous Gains, Europe Is Falling Behind US in Gene Therapy Research’ (Rare Disease Advisor, 26 January 2024) accessed 31 December 2024.
EMA/CAT/841175/2022 (20 October 2022), 4.
The US statistics do not distinguish between gene and cellular therapy products. See US Food & Drug Administration, ‘Approved Cellular and Gene Therapy Products’, content current as of 30 June 2023 accessed 31 December 2024. For better comparison, in Europe in the period 2009-2022, four tissue engineered products (from which two were maintained authorised) and three somatic cell therapy products (from which one was maintained authorised) were registered in the category for ATMPs besides the 16 gene therapy products mentioned.
Wilsdon and others (n 48) 61.
Zhou and Wang (n 29) 3.
See Wilsdon and others (n 48) 1 (stating that Europe falls behind the US and Asia in its R&D investment in gene therapies).
Wilsdon and others (n 48) 62 (stating that Europe performs strongly in academic research for ATMPs); Julia Dahm, ‘German researchers welcome national, EU support for gene therapy research’ (Euractiv, 30 November 2023) accessed 31 December 2024 (citing Professor Sarah Hedtrich, Charité’s Berlin Institute of Health, that there is generally sufficient support for academic research into gene therapies). See also Jakka and Rossbach (n 31) 1 (‘The greatest challenges are economic, not scientific.’).
For the distinction between push and pull incentives in the life sciences industry, see Michael Kremer and Rachel Glennerster, Strong Medicine. Creating Incentives for Pharmaceutical Research on Neglected Diseases (Princeton UP 2004) 45 ff.
Dahm (n 58).
Wilsdon and others (n 48) 62; Marta Iraola, ‘EU needs to step up to unleash gene therapies potential, stakeholders say’ (Euractiv, 27 October 2023) accessed 31 December 2024.
BioSpace, ‘Gene Therapy Market Size Poised to Surge USD 52.40 Billion by 2033’ (BioSpace, 18 April 2024) accessed 31 December 2024.
Wilsdon and others (n 48) 61.
See EMA, ‘EMA pilot offers enhanced support to academic and non-profit developers of advanced therapy medicinal products’ (EMA, 29 September 2022) accessed 31 December 2024.
art 27(1) TRIPS. See also Peter de Lange, ‘Article 53 EPC’ in Kaisa Suominen and others (ed), Visser’s Annotated European Patent Convention (Wolters Kluwer 2024) n 3 (starting that therapeutic, surgical and diagnostic methods constitute inventions). For the general distinction between product and process claims see, for example, Sirpa Soini, Ségolène Aymé and Gert Matthijs, ‘Patenting and licensing in genetic testing: ethical, legal and social issues’ (2008) 16 European Journal of Human Genetics S10, S20.
The exception also covers such treatments and diagnostic methods relating the animal bodies.
For its genesis, see, for example, T 0385/86, r.3.1 with further references to the preparatory materials.
Federal Court of Justice (BGH), [1968] GRUR 142, 145 f – Glatzenoperation. Since the beginning of the 20th century, the German practice denied patent protection for therapeutic methods. See German Patent Office, Bl. f. PMZ 1905, 4 – Badewasser. There were discussions on the legal basis as the German Patent Act did not enshrine a specific exception. For an overview of the early developments in German law, see Hans Dersin, ‘Über die Patentfähigkeit von Verfahren zur Behandlung des lebenden menschlichen Körpers (Dauerwell- u. Haarfärbeverfahren)’ [1951] GRUR 2.
Glatzenoperation (n 68).
Julia Eisenkolb, Die Patentierbarkeit von medizinischen insbesondere gentherapeutischen Verfahren (Duncker & Humblot 2008) 60; Rainer Moufang, ‘Medizinische Verfahren im Patentrecht’ [1992] GRUR Int 10, 15 (also reporting that an attempt, particularly of the UK and Ireland, to move the exclusion at least in the Implementing Regulations to the EPC, to allow for its easier amendment or repeal, remained unsuccessful).
EPO, Special Edition No 4 to OJ EPO 2007: Revision of the European Patent Convention (EPC 2000) Synoptic presentation EPC 1973/2000 – Part I: The Articles, 58;
G 1/04, r.10; G 0002/08, r.5.6. Even the German legislator realized this fact although German law had followed the approach of the decision Glatzenoperation for decades: BT-Drs. 16/4382, 11. For a discussion on the true objectives of the exclusion, see V.2. below.
Julian L Hacker, Die fehlende Legitimation der Patentierungsausschlüsse (Mohr Siebeck 2015) 133. For a definition of liberal profession, see for example, Recital 43 of DIR 2005/36 (defining a liberal profession as those practiced on the basis of relevant professional qualifications in a personal, responsible and professionally independent capacity by those providing intellectual and conceptual services in the interest of the client and the public).
CA/PL 7/99 e.
EPO, Special Edition No 4 to OJ EPO 2007: Revision of the European Patent Convention (EPC 2000) Synoptic presentation EPC 1973/2000 – Part I: The Articles, 58; G 0002/08, r.5.5;
de Lange (n 65) n 3.
See Section V.1. below.
Kurt Haertel, ‘Die Harmonisierungswirkung des Europäischen Patentrechts’ [1981] GRUR Int 479. Specifically, regarding the exception for treatments and diagnostics, Moufang (n 72) 15. For the effect in the UK, see David Bainbridge, Intellectual Property (Pearson 2018) 819 f and Peter Drahos, ‘Biotechnology Patents, Markets and Morality’ (1999) 21(9) EIPR 441, 442 (stating that English courts have pointed out that it is of the ‘utmost importance’ that the exclusions in s 1 of the UK Patent Act should have the same interpretation as the EPO gives to the exclusions contained in art 52 EPC).
In some jurisdictions (see, for example, art 4(4) of the Luxembourg Patent Act), the exception still refers to the lack of industrial applicability.
T 0024/91, r.2.7.
Rainer Moufang, ‘Patentability of pharmaceutical innovations: the European perspective’ in Josef Drexl and Nari Lee (eds), Pharmaceutical Innovation, Competition and Patent Law (Edward Elgar 2013) 54, 61.
EPO, ‘Guidelines for Examination in the European Patent Office’ (March 2024) G-II, 4.2.1 with reference to G 1/04.
Eisenkolb (n 72) 181.
Caleb Bashor and others, ‘Engineering the next generation of cell-based therapeutics’ (2022) 21 Nature Reviews Drug Discovery 655, 658 f. See also GMI, Gene Therapy Market Report 2023, 13 (GMI, May 2023) accessed 31 December 2024 (stating that 71.2% gene therapies are in vitro).
See EP2414844A2 for a European patent granted for biomarkers.
See WO9909193A1, WO0039317A1 for vector patents validated in various European states by the EPO in a PCT procedure.
G 1/04, r.6.2.1; G 0002/08, r.5.6. See also Axel Remde, Christian Ebner and Alfred Köpf, ‘Medical devices and the exclusion from patentability under Art. 53(c) EPC’ [2024] Mitteilungen der deutschen Patentanwälte 161, 166 ff with references to the case law.
G 1/04, r.6.2.1; G 0002/08, r.5.6. See, for example, EPO T 1731/12, r.32. 90 See Ex parte Brinkerhoff, 24 Dec. Comm’r 349 (1883), republished in New Decisions, 27 J. Pat. & Trademark Off. Soc’y 797 (1945). On this case: Eddy Ventose, Medical Patent Law – The Challenges of Medical Treatment (Edward Elgar 2011) 377. A method of medical treatment – a use of surgical instruments for the treatment of a human body – was held to be not patentable. For a historic background of the US methods of treatment patentability, see also Leisa Talbert Peschel,’Revisiting the Compromise of 35 U.S.C. § 287(C)’ (2008) 16 Tex. Intell. Prop. L.J. 321 and Fariba Sirjani and Dariush Keyhani, ‘35 U.S.C. § 287(C): Language Slightly Beyond Intent’ (2005) 3(1) Buffalo Intellectual Property Law Journal 13.
Leading decision from 1883: Ex parte Brinkerhoff (n 90).
103 U.S.P.Q 107.
Ventose (n 90) 374. For a concise reflection on both decisions, see Anne Sophie Wolfrum, Patentschutz für medizinische Verfahrenserfindungen im Europäischen Patentsystem und im US-Recht (Mohr Siebeck 2008) 143 f, 146 f.
For the pro-patent policy during the rise of the CACF, see Robert P Merges, American Patent Law (CUP 2023) 409 ff.
Mayo v Prometheus 566 U.S. 66, 71 (2012) quoting Gottschalk v Benson 409 U.S. 63, 67 (1972).
ibid quoting Diamond v Diehr 450 U.S. 175, 187 (1981).
Mayo v Prometheus 566 U.S. 66, 71 (2012); Alice Corp. v CLS Bank International 573 U.S. 208, 217 f (2014).
Mayo v Prometheus 566 U.S. 66, 72 f (2012); Alice Corp. v CLS Bank International 573 U.S. 208, 217 f (2014).
Alice Corp. v CLS Bank International 573 U.S. 208, 217 f (2014) citing Mayo v Prometheus 566 U.S. 66, 72 f (2012).
Notably, the USPTO and the CAFC initially held that it is not necessary for ‘method of treatment’ claims that practically apply natural relationships to include new and/or inventive steps to be considered patent eligible. See Mateo Aboy and others, ‘One year after Vanda, are diagnostics patents transforming into methods of treatment to overcome Mayobased rejections?’ (2020) 38 Nature Biotechnology 279.
Siva Thambisetty, ‘Alice and ‘something more’: the drift towards European patent jurisprudence’ (2016) 3(3) Journal of Law and the Biosciences 691, 696.
Timo Minssen and Robert M Schwartz, ‘Separating sheep from goats: a European view on the patent eligibility of biomedical diagnostic methods’ (2016) 3(2) Journal of Law and the Biosciences 365, 369.
For this distinction, Mark A Lemley, ‘Ex Ante versus Ex Post Justifications for Intellectual Property’ (2004) 71(1) U. Chi. L. Rev. 129. See also n 112.
William M Landes and Richard A Posner, The Economic Structure of Intellectual Property (Harvard University Press 2003) 14. See also Fritz Machlup and Edith Penrose, ‘The Patent Controversy in the Nineteenth Century’ (1950) 10 Journal of Economic History 1, 21 ff and Fritz Machlup, ‘An Economic Review of the Patent System’ (US Government Printing Office 1958), 23 f (both stating that the incentive-to-invent argument was one of the main arguments for modern patent systems in Europe).
Vincenzo Denicolò and Luigi Alberto Franzoni, ‘The contract theory of patents’ (2004) 23 International Review of Law and Economics 365;
Dominque Guellec, ‘Patents as an Incentive to Innovate’ in Dominique Guellec and Bruno van Pottelsberghe de la Potterie (eds), The Economics of the European Patent System (OUP 2007) 46, 74 f;
Lisa Larrimore Ouellette, ‘Do Patents Disclose Useful Information?’ (2012) 25 Harv. J.L. & Tech. 531. See also Machlup and Penrose (n 110) 25 ff and Machlup (n 110) 24 f (both stating that the incentive-to-disclose argument was one of the main arguments for modern patent systems in Europe).
The standard justification for the patent system is ex ante, before the grant of the patent: Lemley (n 109). For ex post justifications (innovation and transaction function), see the overview at Martin Stierle, Das nicht-praktizierte Patent (Mohr Siebeck 2018) 215 ff, 239 f.
This is particularly true in the life sciences industry. See, for example, Linda Martin and others, ‘How much do clinical trials cost?’ (2017) 16 Nature Reviews Drug Discovery 381, 382 for the median cost of conducting clinical trials (reporting USD 3.4 million for phase I trials involving patients, USD 8.6 million for phase II trials and USD 21.4 million for phase III trials).
Giles S Rich, ‘The Relation between Patent Practices and the Anti-Monopoly Laws’ (1942) 24 J. Pat. & Trademark Off. Soc’y 159, 177 ff;
Scott F Kieff, ‘Property Rights and Property Rules for Commercializing Inventions’ (2001) 85 Minn. L. Rev. 697; Stierle (n 112) 215 ff.
Kenneth J Arrow, ‘Economic Welfare and the Allocation of Resources for Invention’ in NBER (ed), The Rate and Direction of Inventive Activity: Economic and Social Factors (Princeton University Press 1962) 609, 614 ff;
Robert P Merges, ‘A Transactional View of Property Rights’ (2005) 20 Berkeley Tech. L.J. 1477.
See Arrow (n 115) 615 (‘there is a fundamental paradox in the determination of demand for information; its value for the purchaser is not known until he has the information, but then he has in effect acquired it without cost’).
CA/PL 7/99 e, r.1; G 1/04, r.10; G 0002/08, r.5.3;
Special Edition no. 4 to OJ EPO 2007: Revision of the European Patent Convention (EPC 2000) Synoptic presentation EPC 1973/2000 – Part I: The Articles, 58.
G 05/83, r.22; T24/91, r.2.4;
Rainer Moufang, ‘Methods of Medical Treatment Under Patent Law’ (1993) 24(1) IIC 18, 32 f. See also Aaron Kasselheim and Michelle M Melo, ‘Medical-Process Patents — Monopolizing the Delivery of Health Care’ (2006) 355(19) N Eng J Med 2036, 2041 against the patentability of medical procedures. However, they do not discuss the patentability of gene therapy, but mainly focus on patents for molecular tests.
See Section II. above.
See also Gregory F Burch, ‘Ethical Consideration in the Patenting of Medical Processes’ (1987) 65(6) Tex. L. Rev., 1139, 1158 (arguing that ethical objections to medical process patents based on restricted availability of the procedure cannot be maintained when the only alternative is that the procedure never be developed in the first place).
See also O Mitnovetski and D Nicol, ‘Are patents for methods of medical treatment contrary to the ordre public and morality or “generally inconvenient”?’ (2004) 30 J Med Ethics 470, 474 (‘Indeed, every argument raised against methods of medical treatment patents could be equally raised against patents for drugs, medical devices, and cosmetic treatment.’). See also Wolfrum (n 93) 233 f (stating that there is no objective reason to differentiate to exclude methods of treatment, instead all inventions in the field of healthcare would then be excluded) and Hacker (n 74) 127 f (stating that the different treatment of medical products and medical therapies are without justification). See also Sigrid Sterckx and Julian Cockbain, Exclusions from Patentability. How Far Has the European Patent Office Eroded Boundaries? (CUP 2012) 137 (‘purpose of Art. 53(c) EPC is not, and has never been, there to protect the medical practitioner from any accusation of patent infringement since, as the final part of Art. 53(c) EPC and the travaux préparatoires make clear, the tools of the medical practitioner, drugs and equipment, may themselves be patentable’).
Until the 1990s, pharmaceutical product patents were excluded from patent protection in many jurisdictions. See WIPO Standing Committee on the Law of Patents, ‘Exclusions from Patentability and Exceptions and Limitations to Patentee’s Rights’ (SCP/15/3, Annex I) 17 (stating that in 1987, 49 states excluded pharmaceutical products from patentability, while 44 excluded methods of treatment). See also Carlos María Correa, ‘Protection of Data Submitted for the Registration of Pharmaceuticals: Implementing the Standards of the TRIPS Agreement’ (2002) 9 accessed 31 December 2024 (stating that Spain and Portugal did not grant pharmaceutical (product) patents until 1992). These exclusions have since been discarded, at the latest in the aftermath of the adoption of art 27 TRIPS in 1994.
The same is true with Swiss type claims as the EPO BoA and the preparatory materials of the EPC 2000 pointed out. See CA/PL PV 9 e, 7 (arguing that the purpose of the exception – to keep medical practice free from patent law restrictions – was not in fact achieved in practice). Notably, the distinction between patentable second medical use claims and the exclusion of methods for treatment has become vague, as some of the second medical use patent claims direct towards customary aspects of a physician’s practice, like specific individualised dosage instructions or specific administration routes. See for example, T 51/93;
G 0002/08. They also do not contain the ‘manufacturing’ element that was originally covered by Swiss-type claims intended as both conferring industrial application and – relevant to this analysis – the barrier to hold medical practitioners as infringers since doctors regularly do not manufacture the drug. See the Swiss-type claim: ‘Use of a substance/compound X for/in the manufacture of a medicament for treating disease Y/ for the therapeutic application Z.’ After the enactment of the original EPC in 1973, the permitted claim format created by the EPO BoA in a praetorian way by a decision in case G 5/83 was the so-called Swiss-type manufacturing of a substance for a therapeutic purpose – a process claim. The complicated claim construct was created because a product claim was not possible as the substance pertained to the state of the art, but method claim could not be used as it would be equivalent to methods for treatment by therapy claim which feel in the scope of the exception of patentability. Since the revision of the EPC in 2000, the so-called EPC2000 second medical use claim is a purpose-limited product claim.
RobertoRomandini,DiePatentierbarkeitmenschlicherStammzellen: eine vergleichende Betrachtung des europäischen, deutschen und italienischen Patentrechts (Carl Heymanns 2012) 401 ff.
See art 29 UPCA.
Romandini (n 124) 402 f.
CA/PL 7/99 e, 6; T 1020/03, r.46; G 1/04, r.6.1, 6.3; G 0002/08, r.6.5.
Nuno Pires De Carvalho, The TRIPS Regime of Patents and Test Data (5th edn, Wolters Kluwer 2018) para 30.14;
Susanne von Saint-André and Alper Taşdelen in Jan Busche, Peter-Tobias Stoll and Andreas Wiebe (eds), TRIPs. Internationales und europäisches Recht des geistigen Eigentums (2nd edn, Carl Heymanns 2013) art 30 para 32. See, for example, § 11 No 3 German Patent Act. These exceptions are complaint with art 30 TRIPS. As Contracting States can exclude such methods from patentability (art 27(3)(a) TRIPS), a fortiori, they may adopt a corresponding exception to the exclusive rights of the patentee.
During the drafting of the EPC, it was discussed to add a similar exclusion from infringement to the EPC (see Doc 6498/IV/64-E, Section 3: 13; 37).
See Leisa Talbert Peschel, ‘Revisiting the Compromise of 35 U.S.C. § 287(C)’ (2008) 16 Tex. Intell. Prop. L.J. 321, 314 ff.
Inserted by Annex No 2 of the FA of 18 March 2016, in force since 1 January 2019 (AS 2017 2745, 2018 3575; BBl 2013 1).
See Eisenkolb (n 72) 229 with further references.
See Section V.1. above.
See DIR 2016/943 on the protection of undisclosed know-how and business information (trade secrets).
art 93 EPC. See CA/PL 7/99 e, 2 (arguing that the removal of the exception would achieve the desired effect that medical methods are disclosed in patent applications to a far greater extent than hitherto, thereby making them accessible to the general public).
See Iraola (n 61).
See the policy objective stated in 35 U.S. Code § 200 (Bayh–Dole Act). See also the signalling function of patents in attracting investments, Carolin Haeussler, Dietmar Harhoff and Elisabeth Mueller, ‘How patenting informs VC investors – The case of biotechnology’ (2014) 43 Research Policy 1286.
Jacob S Sherkow and Christopher Thomas Scott, ‘The Pick-and-Shovel Play: Bioethics for Gene-Editing Vector Patents’ (2019) 97 N.C. L. Rev. 1497, 1502 ff.
For other relevant factors, see for example, Jules Adam, ‘Why are there only 20 cell and gene therapies in Europe?’ (LABIOTECH, updated 24 January 2025) accessed 4 March 2025; Sanne Allers and others, ‘Patterns in the influence of funding and reimbursement on the development and implementation of healthcare innovation: A systematic review’ (2025) 11(1) Journal of Open Innovation: Technology, Market, and Complexity 100490.
David O Tyler, ‘Patent Eligibility and Investment’ (2019) 41 Cardozo L. Rev. 2019, 2066 ff. See also Robert Cook-Deegan and others, ‘Sorry you asked? Mayo, myriad, and the battles over patent-eligibility’ (2024) 11(1) Journal of Law and the Biosciences 1, 24 ff (giving and overview of the relevant literature and providing multiple references).
For example, Patent Eligibility Restoration Act in the 118th Congress (S. 2140 and H.R. 9474). For an overview Congressional Research Service, ‘Patent-Eligible Subject Matter Reform: An Overview’ (4 December 2024) accessed 31 December 2024.
For the negative effects in such situations, see Michael A Heller and Rebecca S Eisenberg, ‘Can Patents Deter Innovation? The Anticommons in Biomedical Research’ (1998) 280 Science 698.
See Section V.1. above.
Critical about the information function of the patent system, Michele Boldrin and David K Levine, ‘The Case Against Patents’ (2013) 27(1) Journal of Economic Perspectives 1, 9.
See also Gervais (n 24) 387 (‘patents require an enabling disclosure, but in the case of pharmaceuticals where disclosure happens early (typically well before human clinical trials) […], the technical jargon [is] too often used to abscond true disclosure obligations’).
See Mark A Lemley, ‘The Myth of the Sole Inventor’ (2012) 110 Michigan L. Rev. 709, 712 ff (describing the patent system as the structure for a patent race and an ‘overwhelming prevalence of simultaneous invention’).
For a positive stance on the information function, see Lisa Larrimore Ouellette, ‘Do Patents Disclose Useful Information?’ (2012) 25(2) Harv. J. L. & Tech. 531; Jason Rantanen, ‘Peripheral Disclosure’ (2012) 74 U. Pitt. L. Rev. 1.
See the principle of technological neutrality in art 27(1) TRIPS and art 52(1) EPC.
In case of prior EU legislation, see the competence of the Administrative Council to amend certain parts of the EPC, to bring it into line with an EU legislation relating to patents (art 33(1)(b) EPC). However, the provision still requires a unanimous decision from all the Contracting States (art 35(3) EPC).
See art 114 TFEU.
See the amendment of point 8 of art 4(2) of the DIR 65/65 mentioned in art 1 point 1 of DIR 87/21.
art 10(1) of DIR 2001/83 and art 14(11) of REG 726/2004.
See Papadopoulou (n 24) 66; Valtere (n 22) 619.
See art 3(1) REG 141/2000 (requiring that the condition affects not more than five in 10 thousand persons in the EU or is intended for a life-threatening, seriously debilitating or serious and chronic condition and it is unlikely that the marketing of the medicinal product would generate sufficient return to justify the required necessary investment without exclusivity, moreover, requiring that there exists no satisfactory authorized method in the EU or, if such method exists, that the medicinal product will be of significant benefit to those affected by that condition).
art 8 REG 141/2000. However, the EU has put forward a proposal to amend the obtaining requirements and term of orphan drug market exclusivity. See Valtere (n 22) 619.
ATMP is a gene therapy medicinal product, a somatic cell therapy medicinal product, or a tissue-engineered product. See the definition in art 2(1)(a) of REG 1394/2007. All ATMP types consist of either living cells or viral vectors and feature a special complexity.
See Recitals 5 and 6 of REG 1394/2007.
See Papadopoulou (n 24) 193 (stating that the regulatory framework of ATMPs does not provide post-grant economic incentives to invest in the development of ATMPs).
Code of Federal Regulations, Title 21 – Food and Drugs, § 314.108 b) (2), (5-year exclusivity) and (4) (iv) (for 3-year exclusivity) New drug product exclusivity accessed 31 December 2024.
Valerie Junod, ‘Drug Marketing Exclusivity Under United States and European Union Law’ (2004) 59(4) Food and Drug Law Journal 479, 510.
cf Trevor Cook, Pharmaceutical Biotechnology and the Law (3rd edn, LexisNexis 2016) 70.
s 7002 (k)(7)(A) Biologics Price Competition and Innovation Act of 2009.
Laura Valtere, ‘The Interaction Between Exclusivity Rights Systems: A Comparative View on Patents and Regulatory Exclusivities’ in Florent Thouvenin and others (eds), Kreation Innovation Märkte – Creation Innovation Markets, Festschrift Reto M Hilty (Springer 2024) 741, 744.
See Valtere (n 22) 619.
Some even state that one of the original objectives of data exclusivity was to compensate for the lack of patent protection for pharmaceuticals in some Member States. See Correa (n 122) 9 with further references. Rather critical about a comparison with intellectual property rights Inesa Fausch, Personalised medicine as a challenge for patent law (Carl Heymanns 2020) para 422.
Patrick Deboyser reported in European Foundation for the Advancement of Medicine in cooperation with the European Commission, ‘Workshop on “Rare Diseases and Orphan Drugs: European Perspective”’ (5 May 1998) 36 accessed 31 December 2024. See also, COM(1998) 450 final, 10 (referring to the market exclusivity as an intellectual property right). See, however, Recital 8 REG 141/2000 (stating that the market exclusivity is ‘without prejudice to existing intellectual property rights’) and art 8(1) REG 141/2000 (stating that the market exclusivity is ‘without prejudice to intellectual property law’), both suggesting that market exclusivity might not be an intellectual property right. See also Robin Feldman, ‘Regulatory Property: The New IP’ (2016) 40 Colum. J.L. & Arts. 53 (‘the new IP’); Gervais (n 24) (‘form of intellectual property’).
See Regional Court Munich I, decision of 4 August 2023, 21 O 6235/23, [2023] GRUR 1439 – Eculizumab (issuing a preliminary injunction). On appeal, the Higher Regional Court Munich, decision of 1 February 2024, 6 U 3303/23e – Eculizumab, set asides the first-instance decision and held that the regulatory exclusivity is not an absolute, exclusive right that can be enforced between private parties with an injunction. After the Higher Regional Court Munich had set aside the decision, the rightholder pursued the lawsuit on the merits before the Regional Court Munich I which has led to the preliminary reference in the following footnote. In the literature: Ralph Nack and Armin Kühne, ‘Die arzneimittelrechtliche Vermarktungsexklusivität: ein unerkanntes IP-Recht?’ [2018] GRUR Int 1152 (arguing for the market exclusivity to be an intellectual property right);
Marco Stief, ‘Die Marktexklusivität als absolutes Recht (Teil II). Im Kontext der Arzneimittel für seltene Leiden und unter Berücksichtigung der Entscheidungen des OLG München und der vorausgehenden Entscheidung des LG München I ‘Eculizumab’’ [2024] GRUR 1176 (concurring with the Higher Regional Court Munich that the orphan drug market exclusivity is not an absolute right).
Regional Court Munich I, decision of 25 October 2024, 21 O 10225/23, [2024] GRUR-RS 31059 – Eculizumab II. See also: Case C-104/13 Olainfarm v Latvijas Republikas Veselības ministrija, Zāļu valsts aģentūra ECLI:EU:C:2014:2316, where the CJEU assessed whether a holder of an MA or an original product has a subjective right to oppose the MA grant of a generic drug.
The orphan drug protection appears to provide substantial incentives since it has significantly increased therapies available for treating rare diseases. See Denis Horgan and others, ‘Time for Change? The Why, What and How of Promoting Innovation to Tackle Rare Diseases – Is It Time to Update the EU’s Orphan Regulation? And if so, What Should be Changed?’ (2020) 5(2) Biomed. Hub. 1, 3. In Europe, before orphan drug incentives, eight therapies for rare diseases were registered, while after introduction of the specific regulatory exclusivity more than 2,000 candidates were designated as potential orphan drug candidates, of which 190 were authorised. See European Medicines Agency, ‘Annual report on the use of the special contribution for Annual report on the use of the special contribution for orphan medicinal products Year 2020’ (EMA/30719/2021, 15 February 2021) 1, 3. For the US, see also Sudeep Pushpakom and others, ‘Drug repurposing: progress, challenges and recommendations’ (2019) 18 Nature Reviews Drug Discovery 41, 44 (describing that, within the 17 years before the introduction of orphan drug exclusivity (1966-1983) less than 50 drugs for rare diseases were registered in the US, while within 17 years after the introduction, 360 drugs were approved).
See European Commission, ‘Community Register of orphan medicinal products: EU/3/15/1509’ accessed 31 December 2024.
See European Commission, ‘Community Register of orphan medicinal products: EU/3/14/1266’ accessed 31 December 2024.
See art 2(1) in conjunction with art 1(2) of DIR 2001/83/EC. Gene therapies are a process and not a medicinal product.
See art 28(2) REG 1394/2007.
See Claudia Eder and Claudia Wild, ‘Technology forecast: advanced therapies in late clinical research, EMA approval or clinical application via hospital exemption’ (2019) 7 Journal of Market Access & Health Policy 1, 1 (reporting based on available data from 2018 that eight ATMPs were authorised centrally while at least 32 additional ATMPs were made available in certain EU Member States via hospital exemption).
Fausch (n 166) para 438 (referring the required customisation to individual patients).
See Navidad Cuende and others, ‘The puzzling situation of hospital exemption for advanced therapy medicinal products in Europe and stakeholders’ concerns’ (2014) 16 ISCT 1597, 1597;
Alliance for Regenerative Medicine (n 48) 4;
Fermín Sánchez-Guijo and others, ‘Role of Hospital Exemption in Europe: position paper from the Spanish Advanced Therapy Network (TERAV)’ (2023) 58 Bone Marrow Transplantation 727.
Tatjana Ivaskiene, Mykolas Mauricas and Justinas Ivaska, ‘Hospital Exemption for Advanced Therapy Medicinal Products: Issue in Application in the European Union Member States’ (2017) 12 Current Stem Cell Research & Therapy 45; Alisson Hills and others, ‘An assessment of the hospital exemption landscape across European Member States: regulatory frameworks, use and impact’ (2020) 22 Cytotherapy 772; Fausch (n 166) para 439.
European Commission, Health and Consumers Directorate-General, ‘Regulation (EC) No. 1394/2007 on Advanced Therapy Medicinal Products. Summary of the Responses to the Public Consultation’ (SANCO/D5/RSR/iv(2013)ddg1.d5.) 3.1;
Alliance for Regenerative Medicine and others (n 8) 2 f.
European Commission, Health and Consumers Directorate-General (n 179) 3.1.
Papadopoulou (n 24) 192.
Coppens and others (n 17) 2019.
Currently, pharmaceutical regulation of the EU is based on legal transplants from the US. Papadopoulou (n 24) 198, 213, 215, 231 f, 250, 255 criticises that no reference or discussion is provided with regard to any differences between the two jurisdictions that should influence the interplay of regulatory law with the intellectual property rights system.
See n 142. The concerns of the patent community applies to such situations of overlapping regulatory rights by analogy.
See, for example, DIR 2001/83 and REG 141/2000 focusing on medicinal products not medical therapies. See also REG 726/2004 laying down procedures for the authorization and supervision of medicinal products. See also Papadopoulou (n 24) 6 (describing the regulation of the pharmaceutical market in the EU as product regulation).
COM(2023) 192 final.
Proposed art 2(3) in COM(2023) 192 final.
Proposed art 2(4) in COM(2023) 192 final.
Proposed art 2(6) in COM(2023) 192 final.
Proposed art 2(7) in COM(2023) 192 final.
Alliance for Regenerative Medicine and others (n 8) 2.
See Marc Philipp Schauer, ‘Regulatorische Bestimmungen zur Klassifikation und Probleme bei der Zulassung von Advanced Therapy Medicinal Products (ATMPs) in der Europäischen Union’ [2022] PharmR 482, 489 (stating that good manufacturing practices are submarginal unless deployed in large-scale settings).
Alliance for Regenerative Medicine and others (n 8) 5.
See n 177 ff and accompanying text.
Despite being in parts rather critical about the broad scope of the hospital exemption: Papadopoulou (n 24) 248 (‘of central importance’); Hills and others (n 178) 778 (‘important pathway for the provision of much needed therapies for patients with rare and life-threatening conditions’); Fausch (n 166) para 438 (‘key gateway’); Sánchez-Guijo and others (n 177) 727 (‘valuable European legislative initiative that guarantees patient access to […] ATMPs’).
Schauer (n 192) 489.
Proposed art 2(6) in COM(2023) 192 final.
Proposed art 2(4),(6) in COM(2023) 192 final.
Coppens and others (n 17) 2019. See also Hills and others (n 178) 776 (describing, for example, an extremely far-reaching application of the hospital exemption in Germany). See also Fausch (n 166) para 462 (reporting on the replacement of multiphase clinical trials in Japan).
art 8(1) REG 141/2000. On the complexities to assess similarity already COM(1998) 450 final, ‘Proposal for a European Parliament and Council Regulation (EC) on orphan medicinal products’ (27 July 1998) 10.
On compensation payable to the data generator in regulatory law, see Michael J Carroll, ‘The importance of regulatory data protection or exclusive use and other forms of intellectual property rights in the crop protection industry’ (2016) 72 Pest Manag Sci 1631.
See Section III. above.
See Section I. above.
For push programmes in the life sciences industry, see Kremer and Glennerster (n 59) 45 ff.
ibid 55 ff.
Imagine a situation where the patient resides in Luxembourg City and the ATMP is not supplied by the authorization holder in the Grand Duchy of Luxembourg but in Arlon (BE), Metz (FR) and Trier (DE) – all cities within half an hour driving distance. Unless specific circumstances do not allow the patient to travel, the existing supply is sufficient, and EMA should not grant a hospital exemption.
art 3(7) para 2 of DIR 2001/83.
cf Fausch (n 166) para 438.
See art 168(7) TFEU. For an overview of the EU competence in the field of public health, see Papadopoulou (n 24) 10 ff.
