Tuesday, 23 September 2014

T 1616/09 - Different claims, different enablement






Enablement in pharmaceutical claims was central in this Examination appeal. The main request contained the following claims:



1. A pharmaceutical composition comprising a DNA methylation inhibitor; and an anti-neoplastic agent   (...)

20. A combination of a DNA methylation inhibitor and an anti-neoplastic agent (...), for use in a method of treating a disease associated with abnormal cell proliferation.

22. Use of a DNA methylation inhibitor for the preparation of a pharmaceutical composition for treatment of a disease associated with abnormal cell proliferation (...)

36. A kit for treating a disease associated with abnormal cell proliferation, comprising (...)

Based on a cited document the Examining division had concluded that it is unlikely that the combination of drugs had a synergistic effect. As the application did not detail how the combination provided an improvement, the application was refused under Art. 83 EPC and Rule 42(1)(e) EPC (Enablement).


The board did not agree with this application of enablement. The board's decision discusses the requirements for enablement for each of the claim categories. The following catchword was provided:
For the purposes of Article 83 EPC, the level of disclosure in the application which is required for claims directed to pharmaceutical compositions or kits is not the same as that which is required for medical-use claims. For claims directed to pharmaceutical compositions or kits it is in principle sufficient that the application provides information which allows the skilled person to produce the composition or kit, and that there are no substantiated doubts that it could indeed be used in therapy. For second-medical-use claims on the other hand it is required not only that the composition itself is disclosed in an enabling way but also that its suitability for the claimed treatment is plausibly disclosed in the application (Reasons 6).
In the case of a claim directed to a pharmaceutical composition comprising two classes of compounds which have both already been used in therapy in the prior art, there is a priori no reason to doubt that such a pharmaceutical composition can be produced; no specific functional effect has to be demonstrated (Reasons 6.1.1 and 6.1.2).
In the case of second-medical-use claims, if the claimed therapeutic effect was already known to the skilled person at the priority date, it is not necessary to demonstrate it in the application (Reasons 6.2.2).
This decision is also discussed on PatLit.

Reasons for the Decision


2. The examining division objected to the description as not meeting the requirements of Article 83 and Rule 42(1)(e) EPC.

3. Rule 42(1)(e) EPC states that "the description shall describe in detail at least one way of carrying out the invention claimed, using examples where appropriate and referring to the drawings, if any".
Article 83 EPC states that the patent application shall disclose the invention in a manner sufficiently clear and complete for it to be carried out by a person skilled in the art. In other words, the teaching of the application as a whole must enable the skilled person to carry out, without undue burden, the invention which is defined in the claims.

4. In its decision, the examining division referred to the subject-matter not of the claims but of the description. For the purposes of Article 83 EPC as well as of Rule 42(1)(e) EPC, it is the invention, as defined by the claims, which has to be disclosed in the application in an enabling and detailed way. Examination of whether the description, as part of the application, provides such enablement and detail has thus to be done vis-à-vis the claimed subject-matter.

5. The present main request comprises product claims directed to pharmaceutical compositions (claims 1 to 19), as well as claims directed to medical uses, in the format of either purpose-restricted product claims (claims 20 and 21, and dependent claims) or Swiss-type medical-use claims (claims 22 and 23, and dependent claims), and product claims directed to kits (claims 36 to 39).

6. Clearly the level of disclosure which is required for these different categories of claims is not the same. For example, for claims directed to pharmaceutical compositions or kits - which are product claims, not restricted to any specific therapeutic effect - it is in principle sufficient that the application provides information which allows the skilled person to produce the composition or kit, and that there are no substantiated doubts that it could indeed be used in therapy. For second medical-use claims on the other hand it is required not only that the composition itself is disclosed in an enabling way but also that its suitability for the claimed treatment is plausibly disclosed in the application.

6.1 Independent claim 1: Pharmaceutical compositions

6.1.1 Claim 1 is directed to a pharmaceutical composition comprising a DNA methylation inhibitor and an anti-neoplastic agent, wherein the anti-neoplastic agent is further defined by a functional feature, namely that its activity is adversely affected by aberrant DNA methylation. As an example of DNA methylation inhibitors, cytidine analogs are mentioned and specifically decitabine (e.g. application page 7, lines 9 to 12), a compound whose use in therapy had already been disclosed in the prior art (e.g. Schwartsmann G. et al., Investigational New Drugs 18: 83-91, 2000, cited in the European search report). The application also provides a long list of available anti-neoplastic agents (page 1, line 15 to page 6, line 21), and further indicates which anti-neoplastic agents are part of the embodiments of the invention (page 7, line 13 to page 9, line 8); examples of combinations comprising specific groups of anti-neoplastic agents are also disclosed on page 17, line 26 to page 29, line 28. There is no reason to doubt that such products could be formulated as pharmaceutical compositions, since they were indeed individually available in the prior art as such and had also been used in combination (Schwartsmann et al., supra). The board thus considers that the application as filed, and in particular the description, contains sufficient information to enable the skilled person to produce the pharmaceutical compositions as claimed.

6.1.2 The arguments of the examining division were based on an alleged lack of evidence in the application showing that the technical problem as stated in the application - synergistic improvement of the effectiveness of anti-neoplastic agents - had indeed been solved, especially in view of all possible anti-neoplastic agents encompassed in the claims. Since enablement of claims conferring absolute protection for products does not require that any specific functional effect be demonstrated, but rather that the product can be produced, this argument fails. The board agrees that claim 1 has very broad limits, but these are well defined and the skilled person would know without undue burden which compounds were encompassed and which were not: all that is required is to test whether or not the anti-neoplastic activity of the anti-neoplastic agent is indeed impaired by aberrant DNA methylation (a phenomenon which is explained in the application e.g. at pages 12 and 13). The examining division has not provided any arguments, let alone substantiated by facts, that such testing would not be possible without undue burden.

6.2 Independent claims 20 to 23: Medical uses

6.2.1 Claims 20 to 23 are directed to medical uses of combinations of a DNA methylation inhibitor and an anti-neoplastic agent, wherein the medical use is for treating a disease associated with abnormal cell proliferation. By definition, attaining the claimed therapeutic effect is a functional technical feature of claims directed to medical uses. As a consequence, under Article 83 EPC, unless this is already known to the skilled person at the priority date, the application must disclose the suitability of the product to be manufactured for the claimed therapeutic application (T 609/02, reasons 9).

6.2.2 As stated above, the therapeutic application as claimed is treatment of a disease associated with abnormal cell proliferation. Undisputedly, anti-neoplastic agents are, by definition, used to treat cancer, which is an example of a disorder associated with abnormal cell proliferation, and aim, either directly or indirectly and via different mechanisms, at controlling such abnormal cell proliferation: this was state of the art for the present application. Hence, even in the absence of any data in the application showing a therapeutic effect of these agents either on cancer or on other diseases associated with abnormal cell proliferation, there is no apparent reason to doubt that anti-neoplastic agents would have a role in controlling abnormal cell proliferation both in cancer and in other diseases not related to cancer. As such, it can be considered that said claimed therapeutic effect was already known to the skilled person at the priority date and that it therefore does not have to be demonstrated in the application. The fact that the compound to be used consists of a combination with a further substance, namely a DNA methylation inhibitor, does not change this conclusion, unless there were reasons, based on verifiable facts, to believe that this substance would interfere in a negative way with the activity of the anti-neoplastic agent. On the contrary, the teaching of the application is that this further compound may enhance the activity of the anti-neoplastic agent, and this is further supported by the post-published evidence submitted by the appellant with the grounds of appeal (documents D3.1, D3.2, D3.3, D5.10).

6.2.3 The arguments of the examining division concerning an improvement or synergistic effect (supra) are also not valid for these claims, as these claims do not require such an effect. Such an argument could be of relevance in the discussion of inventive step, but not of sufficiency of disclosure.

6.2.4 As regards D4.1, cited by the examining division as an example that one of the combinations falling within the limits of the claim (decitabine plus IFN-gamma) did not have an effect, the board follows the appellant's arguments that, in fact, this document further supports the concept underlying the invention. D4.1 discloses (page 5222, last paragraph and page 5223, first paragraph) that cell lines which are non-responsive to decitabine do not show a high up-regulation of gene expression in the same genes which are up-regulated in cells that are responsive to decitabine. According to D4.1, the cutaneous melanoma cell lines that are non-responsive to decitabine do not present a high enough up-regulation of gene expression in comparison to the uveal melanoma cell lines. Re-expression of silenced genes is an outcome of the hypomethylating activity of decitabine, and D4.1 regards this difference in re-expression as the reason behind the sensitisation of uveal melanoma cell lines, but not of cutaneous melanoma cell lines, to IFN-gamma by decitabine. Finally, D4.1 does demonstrate that decitabine and IFN-gamma (and also IFN-alpha) had an effect on uveal melanoma cells.

6.3 Independent claim 36: Kits

6.3.1 Although claim 36 is directed to a "kit for treating a disease...", thus raising doubts whether it is directed to a product with no purpose restrictions, or whether it has the scope of a purpose-restricted product claim (see also below), the same considerations as discussed above apply also to this claim. Hence, for the reasons given above, this claim is also considered to fulfil the requirements of Article 83 EPC.

Remittal to the first instance

7. The examining division's decision was based only on Article 83 EPC (in conjunction with Rule 42(1)(e) EPC). Novelty and inventive step thus still have to examined and the board notes that a number of documents have been cited in the search report as X. Moreover, there is no indication on file that other EPC requirements such as Article 123(2) EPC or Article 84 EPC have yet been assessed. In particular, it has to be examined whether all new combinations of features and new dependencies of claims do have a basis in the application as filed. Also some issues of lack of clarity are readily apparent, for example as mentioned above concerning the wording of claim 36, which raises doubts as to the claim category; a similar lack of clarity is also present in claim 19.

8. Although there is no absolute right to have an issue decided upon by two instances, it is also not the function of the board to consider and decide upon issues which have not been examined at all by the department of first instance. The board thus decides to exercise its discretion under Article 111(1) EPC and remit the case to the first instance for further prosecution.

Order
For these reasons it is decided that:
1. The decision is set aside.
2. The case is remitted to the first instance for further prosecution.
 

This decision has European Case Law Identifier:  ECLI:EP:BA:2014:T161609.20140827. The whole decision can be found here. The file wrapper can be found here. Photo by  Lali Masriera obtained via Flickr.


2 comments :

  1. The remittal seems a waste of time, since the ED will still be convinced that the claims lack technical effect. The ED may just change the article number from A 83 to A 56 and give the same decision. In my opinion, the point is the lack of technical effect, not the heading under which that conclusion was arrived at.

    ReplyDelete
  2. I'm afraid that could happen. But you never know.

    ReplyDelete

Statcounter