1. Introduction

2. Legal background

3. Maintenance of DE19756864 in

amended form

4. Revocation of EP1040185

5. Expert opinion and discussion

Editorial

Revocation of European patentfor neural progenitors highlightspatent challenges for inventionsrelating to human embryonicstem cellsBarbara RigbyPatent Attorney, Dehns, London, UK

Cells derived from human embryonic stem cells have great therapeutic

potential. Patents are key to allowing companies that develop methods of

generating such cells to recuperate their investment. However, in Europe,

inventions relating to the use of human embryos for commercial purposes

are excluded from patentability on moral grounds. The scope of this morality

exclusion was recently tested before Germany’s highest court and before the

European Patent Office (EPO), with diverging results. The decision by the

EPO’s Opposition Division to revoke EP1040185 relating to neural precursors

and methods for their generation has received a mixed reception. The deci-

sion has very recently been appealed, and the outcome of this Appeal should

provide more definitive guidance on the scope of the morality exclusion.

Keywords: European Patent Office, exclusion from patentability, human embryonic stem cells,

morality, neural progenitors, patents

Expert Opin. Ther. Patents (2013) 23(11):1395-1398

1. Introduction

The human nervous system appears to have a very limited regeneration potential,which represents a challenge in the treatment of nervous system diseases or injury.One promising therapeutic avenue is the transplantation of healthy neural precur-sors, which are cells that have the ability to develop into mature nervous systemcells. Parkinson’s disease is just one example of the many neurological disordersthat could potentially benefit from such treatment.

There is, however, a shortage of suitable neural precursors. Brain tissue of abortedhuman foetuses may in principle be used, but this approach is severely hamperedinter alia by the limited availability of such tissue. Genetic manipulation has beenused to try to provide larger numbers of neural precursors, but this approach isunsatisfactory because of the associated risk of cancerous growths.

In 1997 and 1998, Professor Brustle filed patent applications to seek protectionfor a method of generating neural precursor cells from human embryonic stem(hES) cells, as well as for the resulting neural precursor cells themselves. These pat-ent applications appear to have been one of the earliest reports of the conditionsunder which hES cells can be coaxed into differentiating into neural precursor cellsin vitro.

Brustle obtained a granted German patent, DE19756864, and a granted Euro-pean patent, EP1040185 [1,2]. However, both patents were challenged post-grantby third parties on moral grounds, because the claimed methods and products alleg-edly involved uses of human embryos for commercial purposes.

10.1517/13543776.2013.845170 © 2013 Informa UK, Ltd. ISSN 1354-3776, e-ISSN 1744-7674 1395All rights reserved: reproduction in whole or in part not permitted

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2. Legal background

The patentability of biotechnological inventions in theEuropean Union (EU) is governed by European Directive98/44/EC of 1998, known as the Biotech Directive, whichhas been implemented into national law by EU memberstates, as well as by the European Patent Office (EPO) [3,4].The Biotech Directive states that inventions are not patent-able where their commercial exploitation would be contraryto public order or morality, and it specifically prohibits theuse of human embryos for commercial or industrial purposes.However, the Biotech Directive neither provides a definitionof the term ‘human embryo’, nor does it explain what actsconstitute the ‘use of a human embryo’. This has createduncertainty surrounding the patentability of inventions relat-ing to hES cells.In a landmark case in 2008, the Enlarged Board of Appeal,

the highest authority of the EPO, held that inventions whichnecessarily require the destruction of a human embryo arenot patentable [5]. However, European patents could beobtained for inventions which from the filing date of the pat-ent could be worked using an existing hES cell line. hES celllines are in vitro cultures of hES cells that were originallyderived from an embryo, but which are subsequently main-tained and propagated in a laboratory to provide an essentiallyunlimited supply of hES cells.However, in 2011, in response to questions referred to it by

the German court handling DE19756864, the Court of Jus-tice of the EU (CJEU) unsettled patent practice when itheld that it is immaterial how far removed the destructionof a human embryo is from the invention [6]. Thus, accordingto the CJEU, the exclusion applies not only to those inven-tions that directly involve the destruction of an embryo butalso to those requiring the use of an hES cell that was origi-nally derived through the destruction of a human embryo.Consequently, any methods or products that involve as theirbase material cells taken from an established hES cell linewhich was originally obtained through the destruction of ahuman embryo are apparently excluded from patentability,no matter how long ago the hES cell line was originallyestablished.With regard to the meaning of the term ‘embryo’, the CJEU

held that this encompasses inter alia any fertilised egg from the

moment of fertilisation and including all subsequent stages

during the process of the development and formation of the

human body, including the blastocyst stage from which embry-

onic stem cells are typically retrieved; as well as any other cell

capable of commencing the process of development of a

human being, such as a human egg into which the genetic

material of an adult human cell has been introduced. However,

the CJEU left it to the national courts to ascertain whether an

hES cell itself should be considered to be a human embryo.The CJEU’s ruling is binding on all EU member states and,

for example, the UK Patent Office issued a practice note

reflecting the decision of the CJEU [7]. Although the EPO isnot bound by the ruling, it too changed its practice accord-ingly [8]. Following the CJEU ruling, the validity of Brustle’spatents was considered by the German Federal SupremeCourt (Bundesgerichtshof) and by the EPO respectively.

3. Maintenance of DE19756864 in amendedform

In November 2012, the Bundesgerichtshof of Germany, hav-ing considered the ruling of the CJEU, held DE19756864 tobe valid in amended form [9].

The Bundesgerichtshof ascertained that an hES cell that hasbeen obtained from a human embryo should not be regardedas a human embryo.

It ruled that the exclusion from patentability under themorality provisions may be avoided by limiting patent claimssuch that precursors which were obtained from humanembryonic stem cells obtained by destroying human embryosare not encompassed within the scope of the claims.

The Bundesgerichtshof accepted Brustle’s argument thatthe claimed invention could be carried out using humanembryonic germ cells, that is, the cells that give rise to eggsor sperm, which may be isolated from aborted foetuses. Itwas therefore satisfied that it was possible at the filing dateof the patent to carry out the method of the invention withoutdestroying a human embryo.

The Bundesgerichtshof therefore allowed the grantedclaims to be amended to include provisos which set out thatthe claimed methods do not encompass the use of humanembryonic stem cells obtained by destroying human embryos;and that the claimed products do not include precursor cellsgenerated from human embryonic stem cells obtained bydestroying human embryos. It ruled that the patent soamended does not contravene the morality provisions ofGerman patent law.

4. Revocation of EP1040185

European Patent application number 98966817.3 granted asEP1040185 in 2006 after the claims were amended toincluded a proviso that the ‘method does not include thedestruction of human embryos’ to address objections raisedunder the morality provisions.

The patent was opposed inter alia for allegedly contraven-ing the morality provisions of European patent law, extendingbeyond the scope of the application as filed and being insuffi-ciently disclosed [4,10,11]. Brustle requested the maintenance ofthe patent as granted. As an auxiliary request, a claim set witha slightly revised proviso was filed.

The Opposition Proceedings attracted a great deal ofattention and observations were filed by a number of differentparties, including Greenpeace, the European Patent Instituteand the Dutch Biotechnology Association, some of whichurged the EPO not to adopt a more restrictive interpretation

B. Rigby

1396 Expert Opin. Ther. Patents (2013) 23(11)

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of the morality provisions than the German Bundesgericht-shof had done [12]. However, in April 2013, the EPO revokedEP1040185 [13].

The EPO considers that a paper published in 2008 was thefirst report of a method of obtaining hES cells withoutdestroying a human embryo, and that therefore at the filingdate of the Brustle patent (1998), no method of obtaininghES cells without destroying a human embryo was known [14].Unlike the Bundesgerichtshof, the EPO rejected the argumentthat embryonic germ cells are equivalent to embryonic stemcells. Consequently, the Opposition Division ruled that atthe filing date of the patent, it would not have been possibleto work the invention without destroying a human embryo.

Technically, the Opposition Division’s decision to revokethe patent was based on Article 123(2) (the so-called ‘addedmatter’ provisions) of the European Patent Convention,under which patents may not be amended such that theyextend beyond the scope of the application as filed. However,it is clear that the Opposition Division’s decision was drivenby a consideration of the morality provisions.

Brustle has filed an appeal against the EPO’s decision torevoke EP1040185. At the time of writing, the reasonedgrounds of appeal had not yet been filed.

5. Expert opinion and discussion

Given that the German Bundesgerichtshof, which is bound bythe ruling of the CJEU, decided to allow the patent inamended form, it is somewhat surprising that the EPO, whichis under no obligation to follow the ruling of the CJEU, tooka stricter line than the Bundesgerichtshof.

It appears that different definitions of hES cells may haveplayed a pivotal role in these cases. The Brustle patent assertsthat the term ‘hES cells’ includes human embryonic germcells. This definition was accepted by the Bundesgerichtshof,satisfying it that at the filing date of the patent the skilled per-son was provided with at least one way of carrying out theclaimed invention, namely by using human germ cells. Bycontrast, the EPO held that whilst it is permissible to a certainextent for patent applicants to write their own dictionary in apatent application, defining germ cells as embryonic stem cellsgoes too far. Consequently, the EPO did not accept that theinvention could be worked by using germ cells. It remainsto be seen whether the German decision hinges on the partic-ular facts of this case, or whether similar patents that do notinclude any references to germ cells will also be allowablein Germany.

Questions are being raised as to whether the EPO was rightto let the ruling of the CJEU prompt a change in the practicethat had been established as a result of a ruling of the EPO’sown Enlarged Appeal Board. It is expected that this and otherissues pertaining to the scope of the morality provisions will indue course be considered by the EPO’s Appeal Board forexample as part as the appeal against the revocation ofEP1040185. A further appeal relating to the patentability of

inventions concerning hES cells is also currently pendingbefore the EPO and there is hope that this issue will eventu-ally be put to the EPO’s Enlarged Board of Appeal for moredefinitive guidance and greater legal certainty [15].

In the meantime, it is important to appreciate that the EPOconsiders that a report published in February 2008 provides amethod of isolating hES cells without destroying a humanembryo [14]. Consequently, patent applications relating tohES cells filed since February 2008 are typically outside ofthe exclusion from patentability on moral grounds.

The determination by the German Court that hES cells donot constitute a ‘human embryo’ has been welcomed, but theprecise scope of the term ‘human embryo’ remains a grey area.A recent further referral to the CJEU in this regard is likely toimpact on future practice in this field [16].

It is also worth examining whether there is a risk that thelaws which were introduced to implement the Biotech Direc-tive may be taking on a direction that is not in line with theaims of the Directive. A key aim of the Biotech Directivewas to harmonise biotech patent law across the EU and toclarify what subject matter is patentable and what is not.The divergent decisions of the German Bundesgerichtshofand the EPO signal that at least for now we are a long wayoff harmonisation of this issue across Europe.

Another key aim was to prevent the patenting of inventionswhich are contrary to morality and to exclude uses of humanembryos for industrial or commercial purposes from patent-ability. In the author’s opinion, this exclusion was nevermeant to prohibit the patenting of inventions that can bepracticed by using hES cells from an established hES cellline. The laws of most EU member states governing stemcell research and funding therefore make a clear distinctionbetween work that necessitates the use of a human embryoand work on hES cell lines; indeed, in many of these countriesthe use of cells from existing hES cell lines is encouraged toprevent the use of embryos [17]. It is a pity that the EPO’srecent revision of the Guidelines and the revocation ofEP1040185 signal that the EPO nevertheless considers theuse of hES cell lines established prior to February 2008 tobe contrary to morality. It remains to be seen whether thesetrends will be reinforced or reversed by the EPO’s AppealBoards.

The Brustle cases have fanned the debate as to why Euro-pean patent law includes any morality provisions at all. Itwould appear that the introduction of the morality provisionswas at least in part motivated by a desire to avoid the patentsystem from being seen to endorse morally questionableinventions. However, it must be appreciated that a patentdoes not automatically give the patent owner the right to prac-tice his invention. Instead, a patent is a negative right, whichallows the patent holder to stop others from working the pat-ented invention. Paradoxically, the morality provisions mayarguably be at risk of increasing the amount of research thatis carried out on human embryonic stem cells, because theyweaken the patent barriers to such work. Perhaps it would

Revocation of European patent for neural progenitors highlights

Expert Opin. Ther. Patents (2013) 23(11) 1397

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have been more appropriate to try to educate the public aboutthe rights afforded by a patent, and to leave the determinationof what is morally acceptable to legislators in non-patentfields. However, the morality provisions are firmly enshrinedin European patent law, so the challenge is to determinehow these provisions should be interpreted and applied. It isthe author’s hope that European patent practice will developto allow the patenting of inventions that can be practiced byusing hES cells from any established hES cell line, but it

remains to be seen what view the EPO’s Appeal Boards andperhaps higher instances take on this matter.

Declaration of interest

B Rigby is employed at Dehns, Patent and Trademark Attor-neys. The author states no conflict of interest and has receivedno payment in preparation of this manuscript.

BibliographyPapers of special note have been highlighted as

either of interest (�) or of considerable interest(��) to readers.

1. DE19756864 (known as the German

Brustle patent). Available from: https://

register.dpma.de/DPMAregister/pat/

PatSchrifteneinsicht?docId=

DE000019756864C1&page=1&

dpi=150&lang=en

2. EP1040185 (known as the European

Brustle patent). Available from: http://

worldwide.espacenet.com/

publicationDetails/originalDocument;

jsessionid=5F9F47DEBE74EFC9E5FA3A

09D4BF6F4C.espacenet_levelx_prod_3?

FT=D&date=20060222&

DB=&locale=en_EP&CC=

EP&NR=1040185B1&KC=B1&ND=1

3. European Directive 98/44/EC of 1998

(known as the Biotech Directive)

4. Morality provisions of European patent

convention (Article 53(a) and Rule 28(c)

EPC)

5. Decision G2/06 of the EPO’s Enlarged

Board of Appeal (also known as the

“WARF” case)

6. Decision C34/10 of the Court of Justice

of the EU

7. Practice Note of the UK Intellectual

Property Office. Available from: http://

www.ipo.gov.uk/p-pn-stemcells-

20120517.htm

8. EPO Guidelines for Examination G-II,

5.3

9. Decision X ZR 58/07 of the German

Federal Supreme Court

(Bundesgerichtshof)

10. Provisions of the European Patent

Convention governing the admissibility

of amendments: Article 123(2) EPC

11. Provisions of the European Patent

Convention governing sufficiency: Article

83 EPC

12. EPO online file wrapper of EP1040185.

Available from: https://register.epo.org/

application?number=EP98966817&

lng=en&tab=doclist

13. Decision of the Opposition Division of

the EPO to revoke EP1040185; 2013

14. Chung Y, Klimanskaya I, Becker S, et al.

Human embryonic stem cell lines

generated without embryo destruction.

Cell Stem Cell 2008;2(2):113-7

15. Appeal pending before the EPO relating

to inventions concerning human

embryonic stem cells: EP1554373 of

Technicon

16. Referral C-364/13 to the Court of

Justice of the EU from the UK High

Court in the case of International Stem

Cell Corporation v. UKIPO General of

Patents [2013] EWHC 807 (Ch).

.. The question referred is: Are

unfertilised human ova whose division

and further development have been

stimulated by parthenogenesis, and

which, in contrast to fertilised ova,

contain only pluripotent cells and are

incapable of developing into human

beings included in the term “human

embryos” in Article 6(2)(c) of

Directive 98/44IEC on the Legal

Protection of Biotechnological

Inventions?

17. Regulation of stem cell research in

Europe. Available from: http://www.

eurostemcell.org/stem-cell-regulations

AffiliationBarbara Rigby PhD

Patent Attorney, Dehns, London, UK

E-mail: brigby@dehns.com

B. Rigby

1398 Expert Opin. Ther. Patents (2013) 23(11)

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