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La brevetabilité des inventions dérivées des cellules souches en Europe : une mise à jour !

Koen VANHALST, Office Européen des Brevets, cabinet De Clercq & Partners

Avec le soutien de :

Patenting in Life Sciences: Stem cells

Liège Créative, May 27, 2014

Koen Vanhalst, PhD European & Belgian Patent Attorney

De Clercq & Partners E. Gevaertdreef 10a B-9830 Sint-Martens-Latem

+32(0)9 280 23 40 +32(0)9 280 23 45 www.dcp-ip.com [email protected]

Patenting hES cells:

q Legal/Moral issues

q History

q Current situation

q Future?

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q History


q Future?


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Art.53 EPC Exceptions to patentability

European patents shall not be granted in respect of: (a) inventions the commercial exploitation of which would be contrary to "ordre public" or morality; such exploitation shall not be deemed to be so contrary merely because it is prohibited by law or regulation in some or all of the Contracting States; (b) plant or animal varieties or essentially biological processes for the production of plants or animals; this provision shall not apply to microbiological processes or the products thereof; (c) methods for treatment of the human or animal body by surgery or therapy and diagnostic methods practiced on the human or animal body; this provision shall not apply to products, in particular substances or compositions, for use in any of these methods.

Moral issues were casted into legal texts

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Rule 28 EPC: Exceptions to patentability (EU Directive 98/44/EC Art. 5)

Under Article 53(a), European patents shall not be granted in respect of biotechnological inventions which, in particular, concern the following: (a) processes for cloning human beings; (b) processes for modifying the germ line genetic identity of human beings; (c) uses of human embryos for industrial or commercial purposes; (d) processes for modifying the genetic identity of animals which are likely to cause them suffering without any substantial medical benefit to man or animal, and also animals resulting from such processes.

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Moral reasons were casted into legal texts

Rule 29 EPC: The human body and its elements (EU Directive 98/44/EC Art. 6)

(1) The human body, at the various stages of its formation and development, and the simple discovery of one of its elements, including the sequence or partial sequence of a gene, cannot constitute patentable inventions. (2) An element isolated from the human body or otherwise produced by means of a technical process, including the sequence or partial sequence of a gene, may constitute a patentable invention, even if the structure of that element is identical to that of a natural element. (3) The industrial application of a sequence or a partial sequence of a gene must be disclosed in the patent application.

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Moral reasons were casted into legal texts

Main questions hence are:

Is a human embryonic stem cell a human embryo ?

and

What is commercial use?

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q History


q Future?


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The WARF case: G2/06: the claims

"1. A cell culture comprising primate embryonic stem cells which (i) are capable of proliferation in vitro [sic] culture for over one year, (ii) maintain a karyotype in which all chromosomes normally characteristic of the primate species are present and are not noticeably altered through culture for over one year, (iii) maintain the potential to differentiate to derivatives of endoderm, mesoderm, and ectoderm tissues throughout the culture, and (iv) are prevented from differentiating when cultured on a fibroblast feeder layer."

Patenting hES cells: history

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The WARF case: G2/06: the issues:

•  The Examining Division refused the application under Article 97(1) EPC 1973 for the reason that claims 1 to 7, 9 and 10 did not comply with the requirements of Article 53(a) EPC 1973 in conjunction with Rule 23d(c) [now 28(c)] EPC, because, as regards the generation of human embryonic stem cell cultures, the use of human embryos as starting material was described in the application as originally filed as being indispensable.

•  The use of a human embryo as starting material for the generation of a product of industrial application (i.e. the claimed embryonic stem cell cultures) meant a use thereof for industrial purposes within the meaning of Rule 23d(c) [now 28(c)] EPC and was thus prohibited under the said provision in conjunction with Article 53(a) EPC 1973.


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The WARF case: G2/06: reasoning:

•  “35. In view of the questions referred, this decision is not concerned with the patentability in general of inventions relating to human stem cells or human stem cell cultures.

•  It holds unpatentable inventions concerning products (here: human stem cell cultures) which can only be obtained by the use involving their destruction of human embryos.”


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The WARF case: G2/06: The answers of the EBA

•  Question 1: Rule 28(c) EPC (formerly Rule 23d(c) EPC) applies to all pending applications, including those filed before the entry into force of the rule.

•  Question 2: Rule 28(c) EPC (formerly Rule 23d(c) EPC) forbids the patenting of claims directed to products which – as described in the application – at the filing date could be prepared exclusively by a method which necessarily involved the destruction of the human embryos from which the said products are derived, even if the said method is not part of the claims.


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The EPO’s practice after G2/06 was:

•  Refuse applications, if having regard to the entire teaching of the application, the human embryonic stem cells (hESC) could at the filing date of the application only be obtained by isolation from human embryos necessarily involving their destruction:

•  Excluded from patentability are claims to process of deriving hESC, hESC as product, method applied to such hESC and any product by applying such a method to these hESCs

•  Allowable applications, if the application disclosed a way to carry out the invention whereby the hESC are not exclusively derived by destroying human embryos (or if such a way must be considered to be part of the standard general knowledge of a person skilled in the art).

•  Methods and products relating to these hESC would be patentable if they comply with all other EPC requirements

•  Patentable are also: “non-human” ESC and adult stem cells


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The Brüstle case: CJ-EU C-34/10

•  Prof. Brüstle holds a European patent on neuronal precursor cells, derived from human embryonic stem cells, for treating patients with neurological disorders such as Parkinson's disease

•  Greenpeace started invalidation proceedings before the German Federal Patent Court (Bundespatentsgericht) to have the patent revoked on the grounds that the use of human embryos for industrial or commercial purposes is excluded from patentability under Article 2 of German Patent Law, implementing the Biotechnology Directive.

•  The German Federal Patent Court partially followed the demand of Greenpeace and partially revoked the patent, after which Professor Brüstle filed an appeal against the decision with the German Federal Court (Bundesgerichtshof). The German Federal Court referred some clarifying questions to the CJ-EU before making its final decision.


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The Brüstle case: The questions referred to the CJ-EU:

1. What is meant by the term 'human embryos' in Article 6(2)(c) of Directive 98/44/EC?

(a) Does it include all stages of the development of human life, beginning with the fertilisation of the ovum, or must further requirements, such as the attainment of a certain stage of development, be satisfied?

(b) Are the following organisms also included:

1. unfertilised human ova into which a cell nucleus from a mature human cell has been transplanted;

2. unfertilised human ova whose division and further development have been stimulated by parthenogenesis?

(c) Are stem cells obtained from human embryos at the blastocyst stage also included?

Patenting hEScells: history

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The Brüstle case: The questions referred to the CJ-EU:

2. What is meant by the expression 'uses of human embryos for industrial or commercial purposes'? Does it include any commercial exploitation within the meaning of Article 6(1) of the Directive, especially use for the purposes of scientific research?

3. Is technical teaching to be considered unpatentable pursuant to Article 6(2)(c) of the Directive even if the use of human embryos does not form part of the technical teaching claimed with the patent, but is a necessary precondition for the application of that teaching,

(a) because the patent concerns a product whose production necessitates the prior destruction of human embryos,

(b) or because the patent concerns a process for which such a product is needed as base material?


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The Brüstle case: The answers of the CJ-EU “Article 6(2)(c) of Directive 98/44/EC of the European Parliament and the Council of July 1998 on the legal protection of biotechnological inventions must be interpreted as meaning that:

- any human ovum after fertilization, any non-fertilised human ovum into which the cell nucleus from a mature human cell has been transplanted and any non-fertilised human ovum whose division and further development have been stimulated by parthenogenesis constitute a ‘human embryo’ within the meaning of Article 6(2)(c) of the Directive.

- it is for the referring court to ascertain, in the light of scientific developments, whether a stem cell obtained from a human embryo at the blastocyst stage constitutes a ‘human embryo’ within the meaning of Article 6(2)(c) of the Directive”


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The Brüstle case: The answers of the CJ-EU

“The exclusion from patentability concerning the use of human embryos for industrial or commercial purposes in Article 6(2)(c) of the Directive also covers use for purposes of scientific research, only use for therapeutic or diagnostic purposes which are applied to the human embryo and are useful to it being patentable”


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The Brüstle case: The answers of the CJ-EU

“The answer to the third question is therefore that Article 6(2)(c) of the Directive excludes an invention from patentability where a technical teaching which is the subject-matter of the patent application requires the prior destruction of human embryos or their use as base material, whatever the stage at which that takes place and even if the description of the technical teaching claimed does not refer to the use of human embryos.”


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The Brüstle case: The reasoning of the CJ-EU

The Court of Justice states in its reasoning that: •  “The fact that destruction (of the human embryo) may occur at a stage

long before the implementation of the invention, as in the case of the production of embryonic stem cells from a lineage of stem cells the mere production of which implied the destruction of human embryos is, in this regard, irrelevant.”

•  “Not to include in the scope of the exclusion from patentability set out in Article 6(2)(c) of the Directive technical teaching claimed, on the ground that it does not refer to the use, implying their prior destruction, of human embryos would make the provision redundant by allowing a patent applicant to avoid its application by skilful drafting of the claim.”


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The Büstle case: To conclude:

•  hES cells = embryo’s: for the national courts to decide, but…

•  Using hES cells for which an embryo was destroyed 8 years ago in order to establish a cell-line = immoral and hence not patentable

•  What about progenitors or differentiated cells derived from such stem cells?

•  Just how far do you have to go back to be moral or immoral?


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Patenting hEScells:


q History


q Future?

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T 2221/10 (Culturing stem cells/ TECHNION) 04/02/2014

“Inventions which make use of publicly available human embryonic stem cell lines which were initially derived by a process resulting in the destruction of the human embryos are excluded from patentability under the provisions of Article 53(a) EPC in combination with Rule 28(c) EPC”

Patenting hES cells: Current status

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T 2221/10 (Culturing stem cells/ TECHNION) 04/02/2014

•  The Board interpreted certain statements in the EBA’s decision G 2/06 (see above) as meaning that “all steps preceding the claimed use of HES cells which are a necessary precondition for carrying out the claimed invention, have to be considered.” The Board noted that G 2/06 did not make a distinction between steps which have been carried out by the inventor or by any other person, or between steps which took place in direct preparation of the experiments leading to an invention and steps having taken place at a point in time further remote from these experiments.

•  The Board concluded that even the embodiment of the invention employing previously established hES cell lines was excluded from patentability


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T1836/10 (Ex-Parte Wurfel 9/04/2013)

•  Applicant tried to exclude the commercial use of the obtained stem cells by introducing an undisclosed disclaimer excluding subject-matter excluded for non-technical reasons under Articles 52-57 EPC, in accordance with Enlarged Board Decisions G1/03 and G2/03.

•  The application claimed a method for obtaining pluripotent embryonic stem cells from a (e.g. human) blastocyst, wherein the blastocyst was not destroyed while performing the claimed method steps.


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T1836/10 (Ex-Parte Wurfel 9/04/2013)

•  According to the ED the subject-matter of the claims encompassed the commercial use of human embryos (i.e. including blastocysts) without any apparent direct benefit for the embryo itself, which is excluded from patentability. According to the Examining Division, the fact that in the claimed method the embryo was not destroyed was irrelevant for this assessment.

•  The Applicant introduced the following disclaimer: “provided that the cells obtained are not used for industrial or commercial purposes”.

•  The Board did not accept this wording under Art. 123(2) and 84 EPC


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Are excluded from patentability:

(iii) Uses of human embryos for industrial or commercial purposes A claim directed to a product, which at the filing date of the application could be exclusively obtained by a method which necessarily involved the destruction of human embryos from which the said product is derived is excluded from patentability under Rule 28(c), even if said method is not part of the claim (see G 2/06). The point in time at which such destruction takes place is irrelevant. When examining subject-matter relating to human embryonic stem cells under Art. 53(a) and Rule 28(c), the following has to be taken into account:

(a) the entire teaching of the application, not only the claim category and wording, and


EPO Guidelines in examination (Part G ChII, 5.3)

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(b) the relevant disclosure in the description in order to establish whether products such as stem cell cultures are obtained exclusively by the use, involving the destruction, of a human embryo or not. For this purpose, the disclosure of the description has to be considered in view of the state of the art at the date of filing. The exclusion of the uses of human embryos for industrial or commercial purposes does not affect inventions for therapeutic or diagnostic purposes which are applied to the human embryo and are useful to it (EU Dir. 98/44/EC, rec. 42).


EPO Guidelines in examination (Part G ChII, 5.3)

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EPO’s 1st instance departments to only allow hES cell-related applications filed as of the cut-off date of January 10, 2008, when the single blastomere biopsy (SBB) process was published by Chung et al. (Cell Stem Cell. 2: 113–117, 2008), based on the notion that the SBB technique for the 1st time offered a manner to practice hES cell-related inventions by employing hES cell lines for which the preparation did not require prior destruction of human embryos


EPO Practice

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q History


q Future?

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UK High Court: further referral to the CJ-EU

In the Brustle case, the CJEU deliberated on the interpretation of the term “human embryo” as it appears in Article 6(2)(c) of the Biotechnology Directive. It concluded that the classification of “human embryo” should also apply to a parthogenetically-activated oocyte in view that it was “capable of commencing the process of development of a human being just as an embryo created by fertilisation of an ovum can do so

Patenting hES cells: Future

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The present referral to the CJEU arises from an appeal against a decision made by the UK Intellectual Property OQce (UK IPO) to refuse two patent applications, and was brought by the Applicant, International Stem Cell Corporation (ISCC). The applications in question claimed methods of producing pluripotent human embryonic stem cell lines from parthenogenetically-activated oocytes (GB 0621068.6) and methods of isolating pluripotent human embryonic stem cell lines from parthenogenetically-activated oocytes (GB 0621069.4).



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“Are unfertilized human ova whose division and further development have been stimulated by parthogenesis, and which, in contrast to fertilized 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 98/44/EC on the legal protection of biotechnological inventions?”



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•  In December 2014, a new Expert Group on the Development and Implications of Patent Law in the Field of Biotechnology and Genetic Engineering was established.

•  The European Commission’s expects that the Group and its individual Members would significantly contribute to the Commission’s better mapping of the current trends characterizing the biotechnology field, and a more precise understanding of the possible challenges deriving from those trends from the patent law angle.


New EC expert group

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•  SACEPO is pointing the EPO that there are limits in interpreting CJ-EU decisions

•  There is also a close collaboration between the EPI Biotech committee and the Biotech Directors of the EPO, in order to streamline examination of patent applications claimig hEScell-reated inventions.

•  ...


SACEPO and EPI build up pressure

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hESCells: patentable?

From: Wikipedia

?X

iPSCells

MSCells

!

CJ-EU: “embryo” =

Inventions using hES

cells

Downstream inventions

depnding on hES cells

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Thank you !

Questions?

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