T 1954/12 - Scope extension and process claim

Key points

• The Board accepts, under Article 123(3) EPC, the change of a granted claim for a cell into a claim for making a product, the method comprising culturing the cell. The issue is that the method claim also provides protection for the directly obtained product (a vitamin K dependent product), which the granted claim for the cell does not. However, that product was already covered by another granted claim, namely claim 4  for a " A method for improving the productivity of vitamin K dependent protein expression in a host cell". 
• " Although the methods of granted claims 4-7 are, in principle, directed to the achievement of a specific effect, namely the improvement in the productivity of VKD protein expression in a host cell, this cannot change the fact that the actual final product obtained by these methods is a VKD protein. Therefore, these claims must be considered as being directed to methods for the production, indeed, an improved productivity, of a VKD protein. Thereby, the protection conferred by these claims extends, in accordance to Article 64(2) EPC, to the product obtained, i.e. a VKD protein." 
• As a note, claim 4 does not expressly recite the step of culturing the host cell. A method of modifying a host cell to make it capable of producing more protein, seems different from a method of culturing the modified host cell.

T 1954/12 -  link

VIII. Claims 3 to 7 as granted read as follows:

"3. A cell that contains and expresses a recombinant nucleic acid comprising a nucleic acid encoding vitamin K epoxide reductase operatively associated with a heterologous promoter."
4. A method for improving the productivity of vitamin K dependent protein expression in a host cell, comprising the steps of:
(a) introducing into a host cell a nucleic acid encoding a vitamin K dependent protein;
(b) introducing into the host cell a recombinant nucleic acid encoding a vitamin K epoxide reductase (VKOR) and a recombinant nucleic acid encoding a vitamin K dependent carboxylase; and
(c) expressing the nucleic acids of steps (a) and (b).
5. A method for improving the productivity of vitamin K dependent protein expression in a host cell, comprising the steps of:
(a) providing a host cell that expresses a nucleic acid encoding a vitamin K dependent protein;
(b) introducing a recombinant nucleic acid coding for a vitamin K epoxide reductase (VKOR) into the host cell and a recombinant nucleic acid encoding a vitamin K dependent carboxylase; and
(c) expressing the nucleic acids of steps (a) and (b).
6. A method for improving the productivity of vitamin K dependent protein expression in a host cell, comprising the steps of:
(a) providing a host cell that expresses a heterologous nucleic acid encoding a vitamin K epoxide reductase (VKOR);
(b) introducing a nucleic acid coding for a vitamin K dependent protein into the host cell and a nucleic acid encoding a vitamin K dependent carboxylase; and
(c) expressing the nucleic acids of steps (a) and (b).
7. A method according to any one of claims 4, 5 or 6 wherein the nucleic acid encoding the Vitamin K dependent protein is selected from the group comprising factor VII, factor IX, factor X, prothrombin, Protein C and Protein S."

IX. The main request consists of three claims which read as follows:

"1. A cell that contains and expresses a recombinant nucleic acid comprising a nucleic acid encoding vitamin K epoxide reductase operatively associated with a heterologous promoter, and further contains and expresses a heterologous nucleic acid encoding vitamin K dependent carboxylase and expresses a nucleic acid encoding a vitamin K dependent protein, wherein said vitamin K epoxide reductase converts vitamin K epoxide to vitamin K.
2. A method of making a vitamin K dependent protein which comprises culturing a host cell that expresses a nucleic acid encoding a vitamin K dependent protein in the presence of vitamin K and produces a vitamin K dependent protein, and then harvesting the vitamin K dependent protein from the culture, the host cell containing and expressing a heterologous nucleic acid encoding vitamin K dependent carboxylase, and the host cell further containing and expressing a heterologous nucleic acid encoding vitamin K epoxide reductase (VKOR).

Reasons for the Decision

Article 123(3) EPC; Claims 2 and 3

5. According to decision G 2/88 (OJ EPO 1990, page 93), "a patent which claims a physical entity per se, confers absolute protection upon such physical entity; that is, wherever it exists and whatever its context (and therefore for all uses of such physical entity, whether known or unknown)". In accordance therewith, it follows that "a claim to a particular use of a compound is in effect a claim to the physical entity (the compound) only when it is being used in the course of the particular physical activity (the use), this being an additional technical feature of the claim. Such a claim therefore confers less protection than a claim to the physical entity per se". Thus, "a change of category from a claim to a physical entity per se ... to a physical activity involving the use of such physical entity, therefore does not extend the protection conferred by the patent, and is admissible" (cf. point 5 of the Reasons). However, a distinction is made between "a patent whose claimed subject-matter is the use of a product to achieve an effect ... [and] ... a patent whose claimed technical subject-matter is a process of manufacture of a product". For this latter case, it is stated with reference to Article 64(2) EPC that "protection is conferred not only upon the claimed process of manufacture, but also upon the product resulting directly from the manufacture" (cf. point 5.1 of the Reasons).

6. Indeed, it is also established in this decision that, when assessing Article 123(3) EPC, "it is the totality of the claims before amendment in comparison with the totality of the claims after the proposed amendment that has to be considered" (cf. point 3.2 of the Reasons). In this context, it is further stated that an amendment may involve "a change of category, or a change in the technical features of the invention, or both". In the latter case, it has to be assessed whether the features concerned are more or less narrowly defined as a result of the amendment (cf. point 4.1 of the Reasons).

7. Granted claim 3 is a product-claim in which the physical entity is a cell that contains and expresses a recombinant nucleic acid encoding a VKOR (cf. point VIII supra). There is no reference in granted claim 3 to the presence of other recombinant nucleic acids, such as those encoding a VKD carboxylase and/or a VKD protein. That means that, although their presence is not excluded, the claim is not limited to a cell obligatory containing them. Contrary thereto, the cell of claim 1 of the main request is further limited by the presence of these two specific nucleic acids and, in this respect, is more narrowly defined and does not extend the protection conferred. This has not been contested in the appeal procedure.

8. Likewise, there is no reference in granted claim 3 to any method of production of the claimed cell and thus, it may be produced by any possible method, including all methods disclosed in the patent. This includes, in particular, a method in which a recombinant nucleic acid encoding VKOR is introduced into a cell simultaneously with two other nucleic acids (encoding a VKD protein and a VKD decarboxylase), and methods in which the recombinant nucleic acid encoding the VKOR is introduced into a cell by following several defined sequential steps. All these methods result in a cell falling within the scope of granted claim 3, characterized solely by the presence of a recombinant nucleic acid encoding VKOR.

9. According to decision G 2/88 (supra), granted claim 3 confers absolute protection upon the claimed cell and a change of category of this claim to a claim directed to the use of this cell is, in principle, admissible and does not extend the protection conferred. Indeed, such a use is the subject-matter of claims 2 and 3, in which the cell of granted claim 3 (with a recombinant nucleic acid encoding VKOR and with two additional recombinant nucleic acids) is used for making a VKD protein. As in granted claim 3, there is no indication in the methods of claims 2 and 3 as regards the method of production of the cell (i.e. whether the recombinant nucleic acid encoding VKOR is introduced simultaneously with the other two recombinant nucleic acids or following several sequential steps). In fact, there is no need for such indication as these claims are directed to the use of the cell of granted claim 3 and not to a method for its production.

10. Following the distinction made for use-claims in decision G 2/88 (supra), the methods of claims 2 and 3 are directed to the manufacture of a particular product, namely a VKD protein, and thus, the protection conferred by these claims is not limited to the claimed process of manufacture but extends also to this product. The protection conferred by granted claim 3 does not extend to this product and, in this regard, the protection conferred by claims 2 and 3 goes beyond the protection conferred by granted claim 3. However, decision G 2/88 (supra) requires to compare the totality of the claims before and after the amendment (cf. point 6 supra). In doing so, the methods referred to in granted claims 4-7 are highly relevant and, the board comes to the conclusion, that they provide protection for the product obtained by the methods of claims 2 and 3 of the main request, namely a VKD protein.

10.1 Although the methods of granted claims 4-7 are, in principle, directed to the achievement of a specific effect, namely the improvement in the productivity of VKD protein expression in a host cell, this cannot change the fact that the actual final product obtained by these methods is a VKD protein. Therefore, these claims must be considered as being directed to methods for the production, indeed, an improved productivity, of a VKD protein. Thereby, the protection conferred by these claims extends, in accordance to Article 64(2) EPC, to the product obtained, i.e. a VKD protein.

10.2 Granted claims 4-7 do not only define the use of a specific cell for a certain purpose, they also contain features related to the production of said cell. In particular, they explicitly refer to several steps concerning the introduction of the three nucleic acids required in the methods of these claims, namely the nucleic acids encoding VKOR, VKD carboxylase and VKD protein. Appellant II argues that depending on the manner in which these steps are carried out, either sequentially or simultaneously, the resulting final product has different properties. In particular, appellant II refers to a different degree or level of carboxylation of the obtained VKD protein. According to appellant II, claims 2 and 3 comprise an embodiment in which all three nucleic acids are introduced simultaneously, which is not covered by granted claims 4-7. This is however contested by appellant I. In any case, following appellant II's argument, the product resulting from this embodiment is different from the product obtained from any of the methods of granted claims 4-7 (wherein several method steps are carried out in a specific sequence or order) and is not covered by the granted claims.

10.3 The board notes, that there is no evidence on file demonstrating that the VKD protein obtained by the "simultaneous" embodiment referred to by appellant II, is structurally different from a VKD protein obtained by the sequential introduction of the three nucleic acids, in whatever chronological order.

10.3.1 Post-published document D29, cited as expert opinion, refers to the transfection of a HEK293 cell line expressing a human Factor X (FX) with recombinant nucleic acids encoding VKOR and a gamma-glutamyl carboxylase (GGCX), either simultaneously or in sequential order. Whereas differences are found in the efficiency of transfection and the number of transfected (resistant) colonies obtained (cf. page 3812, left-hand column, last paragraph), there is no reference to a possible distinction in the level of FX carboxylation obtained, which is disclosed to be "essentially fully carboxylated" (cf. page 3813, left-hand column, first paragraph).

10.3.2 Whilst differences in the levels of carboxylation of VKD proteins are reported in the post-published document D5 (cited as expert opinion), the experiments reported in this document are concerned with the effect of a known inhibitor (calumenin) on the VKOR and VKD carboxylase system. Indeed, these results are also described in paragraph [0002] of the patent, wherein, with reference to methods carried out in presence of an inhibitor (warfarin), a reduced rate of carboxylation is reported. However, this has no bearing whatsoever on the methods disclosed in the patent because results of methods carried out in the presence of an inhibitor cannot be directly extrapolated to methods performed in absence of this inhibitor.

10.3.3 The board agrees with appellant II that the actual conditions and components used in performing these methods may influence the degree of carboxylation of the VKD protein obtained. However, the board also observes that neither granted claims 4-7 nor claims 2 and 3 of the main request are limited to any of these conditions and components. Therefore, also in this respect, the scope of protection conferred by claims 2-3 of the main request is not extended when compared with the protection conferred by the granted method claims 4-7.

11. Thus, it follows that the requirements of Article 123(3) EPC are fulfilled.