Friday, December 26, 2014 T 1441/13 - The difficulty of disclaiming

The examining division considered the claims not to fulfil the requirements of Article 53(a) EPC in combination with Rule 28(c) EPC - no EP patents shall be granted in respect of invention which at the filing date could exclusively be performed by use (involving the destruction) of human embryos for industrial of commercial purposes, including where the implementation of the invention presupposes such a destructive use to have taken place at some point in time before the filing date, whether or not this is described in the application (G 2/06). In appeal, the applicant tried to overcome the objection by introducing disclaimers in two  auxiliary requests, but without success: the "remaining subject-matter" test of G 2/10 was not met, and/or the claims with the disclaimer lacked clarity.

Summary of Facts and Submissions

[...]

VIII. Claims 1 and 5 of the Main Request read as follow:

"1. A method for obtaining polypeptide-secreting cells, comprising culturing pPS cells in activin A to differentiate the pPS cells to form gut endothelium, and culturing the gut endothelium in a mixture of islet cell differentiation factors comprising one or more of cyclopamine, betacellulin, exendin-4, glucagon-like peptide-1, hepatocyte growth factor, nicotinamide, IGF-1, n-butyrate, retinoic acid (all trans), growth hormone, placental lactogen, VEGF, IGF-II, IBMX, wortmannin, gastrin, cholecystokinin, NGF, EGF, KGF, PDGF, Reg or INGAP, thereby obtaining a cell population in which at least 5% of the cells secrete at least one of the following proteins from an endogenous gene: insulin, glucagon, somatostatin, and pancreatic polypeptide."

"5. A method of producing islet cells from primate pluripotent stem cells comprising

1) differentiating pPS cells to gut endoderm by culturing the pPS cells in a medium comprising activin A or retinoic acid;

2) differentiating the gut endoderm to a pancreas precursor by culturing the gut endoderm in a medium comprising a TGFß antagonist, a member of FGF family and EGF; and

3) differentiating the pancreas precursor to a mature islet cell by culturing the pancreas precursor in a medium comprising nicotinamide."

wherein "pPS" stands for "primate pluripotent stem". Claims 2-4 and 6-11 were directed to preferred embodiments of claims 1 and 5, respectively.

IX. Claims 1 and 5 of Auxiliary Request 1 were identical to claims 1 and 5 of the Main Request except for the following disclaimer at the end of both claims:

"... wherein said pPS cells are not obtained by means of a process in which human embryos are destroyed."

[..,]

X. Claims 1 and 5 of Auxiliary Request 2 were identical to claims 1 and 5 of the Main Request except for the following disclaimer at the end of both claims:

"... wherein the method does not involve use of a human embryo for industrial or commercial purposes."

[...]

Reasons for the Decision

Main Request

1. The Main Request is identical to the request on which the examining division decided to refuse the present application.

Article 53(a) EPC, Rule 28(c) EPC

2. The method of claim 1 for obtaining polypeptide-secreting cells requires the use of a culture of primate pluripotent stem cells (pPS) which, according to the description of the application, includes human embryonic stem (hES) cells (cf. page 6, lines 19 to 20 of the application as filed). In the decision G 2/06 (supra), the Enlarged Board of Appeal considered that "(b)efore human embryonic stem cell cultures can be used they have to be made" and that, if the "only teaching of how to perform the invention to make human embryonic stem cell cultures is the use (involving their destruction) of human embryos, this invention falls under the prohibition of Rule 28(c) EPC" (cf. G 2/06, supra, point 22 of the Reasons). The Enlarged Board of Appeal further decided that the argument of the appellant that, for the assessment of patentability of these inventions, "all the steps preceding an invention for the purposes of Rule 28(c) EPC" should not be taken into account, was not relevant. Thus, the Enlarged Board decided that these steps had to be considered (cf. G 2/06, supra, point 23 of the Reasons).

3. At the relevant date of the patent in suit, the known and practised method for achieving cultures of hES cells, i.e. the starting material of the method of claim 1, included preceding steps that involved the destruction of human embryos. These destructive methods are not excluded from the scope of claim 1. Thus, in accordance with decision G 2/06 (supra), the board decides that the Main Request is not allowable under Article 53(a) EPC and Rule 28(c) EPC.

Admissibility of Auxiliary Requests 1 to 4 and of the new documentary evidence

[...]

Auxiliary Request 1

8. Claims 1 and 5 of Auxiliary Request 1 contain a disclaimer that excludes methods involving the destruction of human embryos, reading: "... wherein said pPS cells are not obtained by means of a process in which human embryos are destroyed" (cf. point IX supra). This disclaimer intends to overcome the objection raised against the Main Request (cf. points 2 and 3 supra).

9. The criteria for allowability of disclaimers have been laid down in the decisions of the Enlarged Board of Appeal G 1/03 (supra, see in particular point 2.4.1 of the Reasons) and G 2/10 (supra). According to decision G 2/10 (supra), the subject-matter remaining in the claim after the introduction of the disclaimer must be - explicitly or implicitly - directly and unambiguously disclosed to the skilled person using common general knowledge, in the application as filed (cf. G 2/10, supra, Headnote answer to question 1(a)). In fact, this is "the overriding principle for any amendment to be allowable under Article 123(2) EPC ... that applies equally to the subject-matter of a claim the scope of which is determined by a disclaimer", be it an undisclosed or a disclosed disclaimer (cf. G 2/10, supra, point 4.7 of the Reasons).

10. In the present case, the subject-matter remaining in claims 1 and 5 of Auxiliary Request 1 after the introduction of the disclaimer, namely a method for obtaining polypeptide-secreting cells which includes the culture of hES cells derived only and exclusively from non-destructive methods, was not available at the priority date of the application (7 December 2001) and thus, was not directly and unambiguously disclosed to a skilled person as required by decision G 2/10 (supra). The board does not consider this "remaining subject-matter" to be disclosed in the application as filed. For the board to arrive at this decision, the following points are relevant:

10.1 According to the appellant, a single hES cell could be obtained from a human pre-implantation embryo by using methods developed in 2000 for pre-implantation genetic diagnosis (PIGD) of in vitro fertilised (IVF) embryos. Document Verlinsky et al. (2001) has been filed in order to show that a single blastomere cell could be obtained from day 3 cleaving embryos without destroying the embryo. This evidence allegedly supports the availability of hES cells at the priority date of the application by methods that do not involve the destruction of human embryos.

10.2 However, for carrying out the methods of claims 1 and 5, it is not enough to be in possession of single hES cells but it is further necessary to culture these cells in order to obtain an established culture of hES cells or a hES cell line, i.e. in vitro culturing and expansion of hES cells (derivation).

It is acknowledged that derivation methods of embryonic stem cells from mice and from some primates were known and available to a skilled person at the priority date of the application, as shown by the bibliographic references in the application as filed cited by the appellant (cf. page 6, third full paragraph and page 8, first and second full paragraphs of the application as filed). However, none of these derivation methods has been successfully used with hES cells.

Indeed, document Klimanskaya et al. (2006) states that the derivation of hES cells "currently requires the destruction of ex utero embryos" (cf. page 481, left-hand column, lines 1-2). Only by using a new method disclosed in this document, it was for the first time possible to obtain two hES cell lines (cf. page 481, right-hand column, last paragraph to page 482, left-hand column, first paragraph). In document Chung et al. (2008), this method is referred to as being highly inefficient (cf. page 1, middle column, first paragraph). Incidentally, Chung et al. (2008) also states that "(t)o date, the derivation of all human embryonic stem cell (hSEC) lines has involved destruction of embryos" (cf. page 1, left-hand column, lines 1-3).

10.3 It is worth noting that the derivation method disclosed in document Klimanskaya et al. (2006) is based on a co-culture of hES cells with green fluorescent protein (GFP)-positive hES cells (cf. page 482, left-hand column, first paragraph). The source of these GFP-positive hES is not mentioned in this document but, in view of the comments made in all these post-published documents (cf. point 10.2 supra), these hES cells were also obtained by methods involving the destruction of human embryos. It is thus only the derivation method disclosed by Chung et al. in 2008, seven years after the priority date of the present application (7 December 2001), which for the first time has allowed the provision of hES cultures (cell lines) without destroying a human embryo in any production step.

11. Appellant's further argument based on the public availability of established hES cell lines cannot be followed by the board, since these cell lines were also originally obtained using methods that, at some preceding step, involved the destruction of a human embryo (cf. point 2 supra, last sentence). This has not been contested by the appellant and there is no evidence on file to demonstrate the contrary.

In this respect, appellant's attention has also been drawn to decision T 2221/10 (supra) (cf. point V supra). In this decision, this board in a different composition considered methods using commercially or otherwise publicly available hES cell lines, including most of the hES cell lines referred to by the appellant in the present case (inter alia, Thomson et al., 1998). Although methods using these hES cell lines did not require de novo destruction of human embryos, the board concluded that all these hES cell lines were initially derived from a process which had destroyed human embryos.

Therefore, the board, following the criteria established in decision G 2/06 (supra), decided that "(i)nventions 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" (cf. T 2221/10, supra, Headnote and points 10 to 29 of the Reasons).

Accordingly, the board dismissed the appeal against the decision of the examining division to refuse European patent application No. 03 751 238.1 claiming the priority dates of 7 October 2002 and 19 February 2003, i.e. almost one year after the priority date of the present application (7 December 2001).

12. Thus, the board does not accept appellant's argument that the application discloses a method for obtaining polypeptide-secreting cells which uses hES cultures or cell lines produced without involving the destruction of a human embryo, in a manner sufficiently clear and complete for it to be carried out - without undue burden or inventive skill - by a person skilled in the art. Rather the methods available to the skilled person at the relevant date all included, at some point in time, the destruction of a human embryo.

13. In view thereof, the board does not consider it necessary to examine whether the disclaimer introduced into claims 1 and 5 of Auxiliary Request 1 fulfils the other criteria established in decision G 1/03 (supra), such as for instance whether the disclaimer is complete, i.e. whether it actually excludes all subject-matter not allowable under Article 53(a) EPC in combination with Rule 28(c) EPC (see in this respect the disclaimer introduced into Auxiliary Request 2, points 15 to 17 infra).

14. In conclusion, the board considers the disclaimer introduced into claims 1 and 5 of Auxiliary Request 1 not to be allowable since the application as filed does not disclose the "remaining subject-matter" of the invention (a method which includes the culture of hES cells derived, only and exclusively, from non-destructive methods). Only with information available seven years after the claimed priority date, a skilled person would have been in a position to put into practice this "remaining subject-matter" (cf. point 9 supra).

Auxiliary Request 1 does not meet the requirements of Article 123(2) EPC.

Auxiliary Request 2

15. Claims 1 and 5 of Auxiliary Request 2 contain a disclaimer reading: "... wherein the method does not involve use of a human embryo for industrial or commercial purposes" (cf. point X supra).

16. Without entering into the question whether this disclaimer overcomes the objection raised against the disclaimer introduced into Auxiliary Request 1 (cf. points 10 and 11 supra), the board considers the disclaimer in Auxiliary Request 2 not to be clear and to be contradictory in itself. The fact that industrial protection is sought for the claimed subject-matter, i.e. a method comprising culturing pPS cells, already indicates that a human embryo is used for industrial or commercial purposes. Thus, claims 1 and 5 of Auxiliary Request 2 are not clear and contravene the requirements of Article 84 EPC.

17. If it is the aim of the introduced disclaimer to restrict the later use of the differentiated pPS cells produced by the claimed method, namely to be used exclusively for the embryo (or the human being derived therefrom) which was used for obtaining the starting material of the claimed method, then the disclaimer is directed to subject-matter which is not covered by the claim. Such disclaimer does not meet the requirements of Article 123(2) EPC is not allowable (cf. T 1836/10 of 9 April 2013, points 11 and 13 of the Reasons).

[...]

This decision has European Case Law Identifier: ECLI:EP:BA:2014:T144113.20140909. The whole decision can be found here. The file wrapper can be found here. Photo "Islets of Langerhans by Sarah Richardson" by University of Exeter obtained via Flickr (no changes made, CC-BY-2.0 license).