Main request (the patent as granted)
1. Introduction - the patent in question
1.1 The patent in suit relates to a molecule, Simalikalactone E (hereinafter SkE), which can be extracted from the plant Quassia amara, and its use as a medicine in the prevention and treatment of malaria (patent, paragraph [0001]).
1.2 It was acknowledged in the patent that the plant Quassia amara had been used in traditional medicine against fevers and malaria throughout the north-western Amazon and as far as Central America. The respondent identified and isolated SkE using a specific method from the (dried mature) leaves of Quassia amara. This molecule was found to be active against malaria (patent, paragraph [0011] and claims 7 and 8).
1.3 Claim 1 of the main request (patent as granted) reads as follows:
"Molecule corresponding to the formula 1 below:
FORMULA/TABLE/GRAPH
1.4 The subject matter of claims 2 to 6 of the main request relates to a medicament comprising the molecule of claim 1.
1.5 Claims 7 and 8 of the main request are worded as follows:
"7. A method of isolating SkE according to claim 1 from Quassia amara leaves.
8. A method according to claim 7 for the isolation of SkE from dried mature leaves of Quassia amara, which comprises the following steps: the dried mature leaves of Q.amara are crushed and extracted with methanol, this extract is dissolved in a two-phase system based on n-heptane, ethyl acetate, methanol, water, the lower phase is collected and its volume is reduced by half by evaporation under reduced pressure, this solution is extracted with ethyl acetate, the ethyl acetate is evaporated, the residue obtained is dissolved in chloroform and washed with a slightly basic aqueous solution, the organic phase is collected, dried and concentrated under reduced pressure, this extract is dissolved in ethyl acetate and washed with water, the organic phase is evaporated under reduced pressure and the residue obtained is eluted with ethyl acetate through a silica column."
2. Public policy - Article 100a) and 53a) EPC
2.1 The appellants submitted that the commercial exploitation of the claimed invention was contrary to good morals and public policy within the meaning of Article 53(a) EPC, since it was not in accordance with morality and with all accepted standards deeply rooted in European culture. These standards concern those governing research with indigenous and local communities and the use of their traditional knowledge.
2.2 In detail, according to the applicants, in the early 2000s, the respondent conducted research on traditional anti-malarial remedies among the populations of French Guiana. As part of this project, a survey was conducted in 2001. 117 people from different communities in French Guiana responded to this questionnaire. The traditional remedies used for the treatment of malaria were collected. The project led to the identification of 45 curative recipes involving the use of 27 species of plants. The researchers studied these traditional remedies and subsequently focused their efforts on studying the plant Quassia amara. As a result, the researchers managed to identify an anti-malarial molecule, SkE.
2.3 These observations were not contested by the respondent and can therefore be considered as facts.
2.4 According to the applicants, the conduct contrary to accepted standards, including those governing research with indigenous communities and the use of their traditional knowledge, constituted a deception of indigenous and local communities and an abuse of their trust for the development of the invention in question. Indeed, it was thanks to the contribution of traditional knowledge that the respondent's researchers were able to identify the SkE molecule. However, the members of the indigenous communities contacted by the respondent were not fully and transparently informed of the nature of the research project, its objectives, the filing of the patent, and other risks and benefits of the project for the members of the communities and their knowledge. Furthermore, their consent regarding the collection of this knowledge and its use was not approved, this being even confirmed by the respondent in press articles (D54 and D55). No benefit sharing was organized between the holders of this knowledge and the researchers of the respondent. The members of the communities had neither the possibility nor the right to decide on the use of their knowledge. As a result, the communities lost control over the circulation of their knowledge with the violation of all intellectual rights over this knowledge.
2.5 The deception and breach of trust by the respondent created a climate that was harmful to research within indigenous and local communities. The commercial exploitation of the claimed invention was likely to cause serious disturbances to public order and jeopardize the relationships of trust between indigenous and local communities and researchers, with serious consequences for the advancement of science. The protection conferred by claim 1 of the contested patent would allow the respondent to prevent indigenous populations from using Quassia amara leaves for the preparation of their traditional remedies. The massive and widespread rejection of the claimed invention was documented with evidence including the reactions of indigenous representatives and other public authorities in French Guiana and France. These testimonies would make it possible to assess the public's perception of the claimed objects.
2.6 Article 53 EPC concerns exceptions to patentability. According to paragraph (a), European patents shall not be granted for inventions the commercial exploitation of which would be contrary to public policy or accepted principles of morality, and such a contradiction cannot be inferred from the sole fact that exploitation is prohibited by a statutory or regulatory provision in all or several of the Contracting States.
2.7 The appellants therefore argued that the claimed invention fell within the scope of the exception provided for in Article 53(a) EPC.
2.8 The Board does not share this view. As indicated by the respondent, none of the appellants' allegations concern the commercial exploitation of the invention, a prerequisite for concluding that the invention would be excluded under Article 53 EPC. On the contrary, the invention claimed in the main request concerns:
- the SkE molecule (claim 1),
- a medicament comprising the SkE molecule (claims 2 to 6), and
- the process for isolating SkE according to claim 1 from the leaves of Quassia amara (claims 7 and 8).
2.9 As the respondent has argued, the commercial exploitation of this molecule, of the drug containing it and of its isolation process is not contrary to morality, good customs or public order. On the contrary, there is a great need for drugs against malaria, and finding new antimalarial drugs is a mission whose aim is to treat populations at risk and save lives.
2.10 The applicants' arguments in this regard did not convince the Board. Citing decision T 356/93, the applicants argued that respect for morality and public policy must be examined in each individual case:
"The question whether a claimed invention constitutes an exception to patentability within the meaning of Article 53(a) EPC will have to be decided on the merits of the case in question, on the basis of the concepts of public policy and morality, ... . The correct approach is to examine the particular facts of each case and to ascertain, in the light of those facts, whether the case is well-founded." (Reasons, point 13, translated from English).
2.11 The appellants then argued that, as in decision G 2/06 of the Enlarged Board of Appeal, when examining the conformity of a patent application with public policy and accepted principles of morality, the EPO could not confine itself solely to the claims as formulated in the patent application. In this sense, therefore, in the present case, it was necessary to examine not only the express wording of the claims, but also "the invention". For the appellants, the "invention" underlying claim 1 included the steps prior to the development of the invention and required for its exploitation, namely the manner, described above, in which the SkE was discovered by the respondent. Thus, the respondent's conduct during the development of the invention and described above (deception and breach of trust, etc.) was linked to the commercial exploitation of the invention. It was then necessary to examine this behavior for the respect of good morals and public order in the specific case of the claimed invention.
2.12 The Board does not share this view. Decision G 2/06 concerned a claim directed to a specific cell culture comprising embryonic stem cells. In determining whether this claim was excluded from patentability, the Enlarged Board concluded that Rule 28(c) EPC, which concerns exceptions to patentability under Article 53(a) EPC for biotechnological inventions, did not refer to "claims" but to an "invention" in the context of its exploitation:
"... this rule does not refer to "claims", but to an "invention" in the context of its exploitation. It is appropriate to examine not only the express wording of the claims, but also the technical teaching of the application as a whole in relation to the manner of implementing the invention. Before using human embryonic stem cell cultures, they must be produced. In the case before the Enlarged Board, the only teaching relating to the manner of implementing the invention in order to obtain human embryonic stem cell cultures is the use (involving their prior destruction) of human embryos." (reasons, point 22)
2.13 In the same way as Rule 28(c) EPC, Article 53(a) EPC refers to an "invention" and not to "claims". However, in the case of G 2/06, the elements likely to be prejudicial to public order and morality, namely the destruction of human embryos, was a prerequisite for the preparation of the claimed cultures. Therefore, this prerequisite was also a requirement for the commercial exploitation of the invention.
2.14 In the present case, the original development of the invention and the historical process by which the SkE molecule was discovered and isolated have no relevance to the commercial exploitation of the present claims, which require only the isolation of SkE from the plant Quassia amara and its administration to patients. The development of an invention is therefore distinct from its commercial exploitation once it has been achieved.
2.15 No evidence has been provided by the applicants that this isolation and its administration would be contrary to public order or morality.
2.16 In writing, but especially during the oral proceedings before the board, the appellants also cited the decision of the opposition division in the "relaxin" case (OJ EPO 1995, 388), and decision T 315/03.
2.17 The "relaxin" decision was cited by the appellants in the same context as G 2/06. Claim 1 related to a DNA fragment coding for human preporelaxin H2. In that decision, it was argued that the subject-matter of the patent was contrary to the provisions of Article 53(a) EPC, insofar as it related to a DNA fragment coding for human relaxin H2 (Reasons, point 6.1). The opponents in that case argued that in order to reproduce, and thus to exploit, the invention, tissue had to be taken from a pregnant woman, which was an infringement of the right to self-determination of every human being (Reasons, point 6.1 (a) and (b)). The Opposition Division considered that, given that the female (DNA) donors had agreed to do so in the context of necessary gynaecological operations, there was no reason to regard this as immoral. Furthermore, there was no need to repeat the procedure for isolating the DNA in order to carry out the invention because it was possible to chemically synthesise the DNA fragment coding for human H2 relaxin (reasons 6.3.1 and 6.3.2). The contested patent was therefore not considered to infringe Article 53(a) EPC.
2.18 In the present case, the appellants argued that, since consent was necessary in the relaxin case to conclude that the claimed subject-matter was not excluded from patentability under Article 53(a) EPC, the same should apply in the present case. Since the consent of the indigenous communities had not been obtained as indicated above, the claimed subject-matter should be excluded from patentability.
2.19 The Board does not share this view. This decision does not indicate that the claimed subject-matter would have been excluded from patentability if consent had not been obtained. Specifically, since it was decided that the initial DNA isolation had been carried out with the consent of the pregnant women. It was therefore not necessary for the Opposition Division to determine whether isolation without consent, even if as such it would have been contrary to public policy or morality, would have been relevant for the claimed subject-matter, the commercial exploitation of which no longer required such a step, and that the claimed subject-matter would therefore have been excluded from patentability under Article 53(a) EPC.
2.20 Rather, the decision states that, contrary to the opponents' arguments about the reproducibility of the invention, there was no need to repeat the procedure for isolating the DNA in order to carry out the invention, since the DNA fragment encoding human H2 relaxin could simply be chemically synthesized (reasons, 6.3.2), and it was only at the initial stage of the invention that a woman was present, as a voluntary donor of the relaxin DNA (reasons, 6.3.3). Therefore, it would seem that in the relaxin case, although not explicitly stated in the decision, the collection of cells from pregnant women was not necessary for the commercial exploitation of the invention.
2.21 Therefore, this decision does not support the appellants' arguments regarding Article 53(a) EPC.
2.22 The appellants also cited decision T 315/03. This decision concerns inventions which are not patentable under Article 53(a) EPC because they fall within one of the categories set out in Rule 28 EPC, which concerns exceptions to patentability under Article 53(a) EPC for biotechnological inventions. It was cited by the appellants to argue that an invention which does not fall within one of the categories set out in Rule 28 EPC must be examined under Article 53(a) EPC.
The Board agrees. However, as stated above, the exception to patentability under Article 53(a) EPC concerns the commercial exploitation of the invention, not the manner in which it was discovered or developed.
2.23 Therefore, even if the respondent's conduct during the discovery and development of the invention as described by the appellants above were considered to be contrary to good morals and public policy, this does not concern the commercial exploitation of the invention, and therefore does not constitute a reason to exclude the claimed invention from patentability under Article 53(a) EPC.
2.24 The Board therefore concludes that the contested patent does not infringe Article 53(a) EPC. The ground of opposition of Article 100(a) in conjunction with Article 53(a) EPC therefore does not preclude the maintenance of the patent as granted.
3. Novelty – Articles 100(a) and 54 EPC
3.1 The applicants argued that the subject-matter of claims 1 to 6 as granted lacked novelty over documents D2, D3 and D5.
3.2 D2 is an article that describes a study of antimalarial remedies used in French Guiana. The study found that the most commonly used species was Quassia amara alone or in combination with other plant species (D2, page 357, "Table 1", and right column, second paragraph). D2 describes that this plant is used in the form of decoctions in water, the ingredients usually being placed in an aluminum pot and boiled for a period of time (page 357, right column, third paragraph). The decoction is then administered orally or is applied to the patient's body (page 357, last paragraph; page 358, first paragraph). D2 does not describe any active molecules and therefore does not explicitly describe the SkE molecule.
3.3 D3 is an article that concerns the evaluation of the antimalarial activity of 23 different species of plants used in French Guiana including Quassia amara (abstract; page 46, penultimate paragraph; page 47, table 1, 'Quassia amara L.'). D3 describes that the decoction prepared with the fresh leaves of Quassia amara is not toxic at 1000 mg/day and can be administered without problem for several days, whatever the active principle (D3, point 4.6, pages 51 and 52). The decoction of Quassia amara leaves is therefore presented as an interesting antimalarial remedy (page 52, left column, first paragraph). Like document D2, D3 does not describe any active molecule, and therefore does not explicitly describe the SkE molecule.
3.4 D5 is a paper that concerns the effect of Quassia amara leaf age and desiccation state on the antimalarial activity of traditional infusions prepared from leaves at different states of maturity and freshness (see page 41, point 2.2, 'Sample preparation'). In a previous study, the molecule Simalikalactone D "SkD" had been identified as the active compound (page 40, 'Introduction'). Four infusions were prepared with fresh young leaves (FJ), dried young leaves (DJ), fresh mature leaves (FM) and dried mature leaves (DM). The concentrations of SkD in each preparation and their antimalarial activity were compared (see page 41, right column, last paragraph and 'Table 1'). The infusion prepared with fresh young leaves (FJ) is the most active and contains a significant amount of SkD (4.63myg/ml; page 42, left column, first paragraph). It is also indicated in D5 that the infusion of dried young leaves has a very potent in vivo activity that does not seem to come solely from the SkD molecule (page 42, point 4, 'Conclusions').
D5 does not describe any other molecule with antimalarial activity, and therefore does not explicitly describe the SkE molecule.
3.5 Documents D2, D3 and D5 therefore do not explicitly disclose the SkE molecule or SkE in combination with other compounds. Rather, these documents disclose traditional antimalarial remedies, i.e. preparations derived from the leaves or stems of a particular plant, Quassia amara.
3.6 The applicants argued that documents D2, D3 and D5 disclosed preparations containing SkE. In this context, the applicants submitted with the statement of grounds of appeal Annex 2, to show, using high-resolution mass spectrometry, the presence of the SkE molecule in the aqueous extract of Quassia amara leaves, thus concluding that SkE must also be present in the extracts of D2, D3 and D5.
3.7 The applicants argued that claim 1 of the main request was not limited to SkE in "isolated" form. It therefore conferred absolute protection on the SkE molecule, in all circumstances and in any context, this protection therefore extending to any preparation, or even any part of a plant, in particular the leaves and extracts of Quassia amara containing the SkE molecule. Therefore, the extracts of D2, D3 and D5 fell within the scope of claim 1 of the main request, and therefore destroyed the novelty of the claimed subject-matter.
3.8 As indicated by the Board during the oral proceedings, it shares the applicants' view regarding the scope of claim 1. Therefore, all compositions containing the SkE molecule including extracts of D2, D3 and D5, to the extent that they contain the SkE molecule, are covered by the scope of claim 1.
3.9 However, the question of whether extracts from D2, D3 or D5 fall within the scope of claim 1 is not the correct criterion for assessing whether the subject-matter of that claim is novel.
3.10 According to Article 84 EPC, the claims define the subject-matter of the protection sought. According to Rule 43(1) EPC, the claims must define, by indicating the technical features of the invention, the subject-matter for which protection is sought. The technical features of claim 1 are the structural features of the SkE molecule.
3.11 According to Article 54(1) and (2) EPC, an invention is considered new if it is not included in the state of the art. The state of the art consists of everything that has been made available to the public before the filing date of the patent application, or the priority date, if applicable (see Article 89 EPC).
3.12 In assessing whether the subject-matter of a claim has been made available to the public and therefore lacks novelty, the "gold standard" has become the commonly used approach as for the addition of subject-matter (Article 123(2) EPC) and the validity of a claimed priority (Article 87 EPC) (see G 1/16, point 17 of the Reasons). It is therefore the only criterion to be applied.
3.13 According to the reference standard, a claim lacks novelty if, taking into account the general knowledge of the person skilled in the art, its subject-matter is disclosed in the prior art explicitly or implicitly, but directly and unambiguously.
3.14 Therefore, even if one accepts the presence of SkE in the extracts of D2, D3 and D5, and even interpreting the scope of claim 1 in the broadest possible manner, as the applicants argue, for example to include the plant Quassia amara and its extracts disclosed in D2, D3 and D5, a direct and unambiguous disclosure of the technical features of claim 1, or even of the SkE molecule alone or in combination with other compounds, is still necessary to conclude a lack of novelty.
3.15 As indicated above, the SkE molecule alone or in combination with other compounds is not explicitly disclosed in documents D2, D3 and D5.
3.16 Furthermore, there is no question of implicit disclosure of the SkE molecule or its combination with other compounds in these documents either. According to the consistent case law of the Boards of Appeal, a prior art document destroys the novelty of the claimed subject-matter if it follows directly and unambiguously from that document, including features implicit for the person skilled in the art. However, an alleged disclosure can only be considered "implicit" if the person skilled in the art immediately recognizes that nothing other than the alleged implicit feature is part of the disclosed subject-matter (see e.g. Case Law of the Boards of Appeal of the European Patent Office, 10**(e) edition 2022, IC4.3). This situation does not apply to the SkE molecule and its combination with other compounds.
3.17 The fact that the SkE molecule may be contained in the extracts of D2, D3 and D5 does not amount to an implicit disclosure either. According to the decision of the Enlarged Board of Appeal in G 2/88 (points 10 and 10.1 of the Reasons), the question is what has been made available to the public, not what could be inherently contained in what has been made available to the public. Even if that decision concerned a use, the same applies in the present case: the presence of the SkE molecule in the leaves of Quassia amara or their decoction has not been made available to the public by the extracts of D2, D3 or D5.
3.18 There is also no implied disclosure of the subject-matter of claim 1 in view of the decision of the Enlarged Board of Appeal in case G 1/92. According to that decision:
"The chemical composition of a product is part of the state of the art when this product as such is accessible to the public and can be analysed and reproduced by a person skilled in the art, regardless of whether it is possible to identify specific reasons for analysing this composition" (conclusion, point 1)
3.19 In the present case, for the prior art to make the SkE molecule available to the public alone or in combination with other compounds, it is necessary for the skilled person to identify the SkE in the extracts of D1, D3 or D5. Since the identification of the SkE represents an excessive effort and therefore involves an inventive step (see below the discussion on inventive step), the SkE is not part of the publicly available prior art. Therefore, also in light of decision G 1/92, the claimed subject-matter is not implicitly disclosed in D2, D3 or D5.
3.20 The Board also noted the referral to the Enlarged Board of Appeal in decision T 438/19. In that case, the question of the possibility of using the product in question (ENGAGE**(®) 8400) in the analysis of inventive step was relevant (reasons for the decision, point 24). In the present case, the question is different, namely whether the disclosure of a product necessarily discloses the components of the extract, more particularly the SkE molecule, which were unknown before the effective date of filing of the patent. In the present case, as indicated above, there can be no implicit disclosure of SkE in said extracts, at least because their identification would involve an excessive effort for the person skilled in the art.
3.21 Therefore, SkE was not disclosed in Documents D2, D3 and D5, and the molecule was not made available to the public through the use of Quassia amara leaves to prepare remedies disclosed in those documents.
3.22 The other arguments of the appellants did not convince the Board. The appellants argued that the subject-matter of a claim could not be considered novel if it was infringed by an existing use, for example, by extracts of D2, D3 or D5. In other words, the protection conferred by the patent would give the respondent the right to prohibit indigenous people from using Quassia amara leaves for the preparation of their traditional remedies.
3.23 The Board disagrees. A similar issue arose in G 2/88. Indeed, it was argued that infringement issues could arise if a finding of lack of novelty was not made at that time: the person making the previously described use was in particular at risk of being sued for infringement of a subsequently filed patent. In response to these allegations, the Enlarged Board of Appeal pointed out that under Article 54(2) EPC the question was what had been "made available" to the public, not what could be "intrinsically contained" in what had been made available. Accordingly, the question of "intrinsically contained" did not arise as such under Article 54 EPC. The Enlarged Board of Appeal also noted that the question of rights based on prior use of an invention was a matter for national law (point 10.1 of the Reasons).
3.24 The subject-matter of claim 1 of the main request, and thus also the subject-matter of claims 2 to 6, is therefore novel. The ground for opposition of Article 100(a) in conjunction with Article 54 EPC therefore does not preclude the maintenance of the patent as granted.
4. Inventive step - Articles 100(a) and 56 EPC
4.1 The applicants argued that the subject-matter of claims 1 to 8 lacked inventive step, starting from document D43 as the closest prior art.
4.2 D43 concerns the evaluation of the antimalarial activity of two plants including Quassia amara in mice. In document D43 extracts obtained from the dried leaves and stem of Quassia amara (abstract) were prepared. According to D43, the extract of the leaves in hexane and methanol shows high activity on Plasmodium berghei, a parasite involved in malaria. The results presented in Table 1 (page 323) show that the extracts of Quassia amara in methanol have a strong antimalarial activity. It is described that animals tested with these methanolic extracts have a longer life span (page 324, right column, second paragraph). D43 also indicates that it would be interesting to isolate the active components of these plants to develop potential antimalarial drugs (page 324, right column, third paragraph).
4.3 The subject matter of claims 1 to 8 is distinguished from D43 by the SkE molecule, its use as a medicament, and its isolation process.
4.4 The objective technical problem
4.4.1 According to the applicants, the technical effect of the claimed SkE was to concentrate the principle which carries the bulk of the antimalarial activity of the Quassia amara leaf extract. The objective technical problem to be solved was to provide a preparation for the treatment of malaria.
4.4.2 The Board disagrees. Although the scope of claim 1 may include preparations as set out above, the technical features of the claim relate to a specific compound. Therefore, the objective technical problem must also include the provision of a compound. Furthermore, as stated by the respondent, and not disputed by the appellants, the SkE molecule has low toxicity (see paragraph 35 of the patent).
4.4.3 The objective technical problem can therefore be formulated essentially as proposed by the respondent, namely to provide a specific compound, or a preparation comprising a specific compound having good antimalarial activity and low toxicity.
4.5 Evidence
4.6 The applicants argued that starting from D43 alone or in combination with D4 or D5, the skilled person, by carrying out conventional and routine procedures for the separation of compounds, would inevitably have come across the SkE molecule. In this context, the applicants referred to the spectra in Annex 2, which showed that there are few different compounds present in an aqueous decoction/infusion of Quassia amara and that the SkE molecule was present in significant quantities.
4.6.1 The Board does not share this view. First, the Board notes that the respondent accepts that D43 suggests to the person skilled in the art to isolate the active compounds from the plants tested. It can also be accepted that D5, cited by the applicants in this regard, also suggests to the person skilled in the art to search for other active compounds from Quassia amara.
4.6.2 However, as the respondent argues, there is no motivation in D43 that could have prompted the skilled person to set up an isolation process that includes the order and sequence of techniques and steps necessary to arrive at a compound whose identity was not known, the SkE molecule. More specifically, the steps necessary to isolate SkE are described in the patent (paragraphs [0042] and [0043]) and are detailed in claim 8 of the main request. This process requires the following steps:
- the dried mature leaves of Quassia amara are crushed and extracted with methanol,
- this extract is dissolved in a two-phase system based on n-heptane, ethyl acetate, methanol, water, the lower phase is collected and its volume is reduced by half by evaporation under reduced pressure,
- this solution is extracted with ethyl acetate, the ethyl acetate is evaporated, the residue obtained is dissolved in chloroform and washed with a slightly basic aqueous solution,
- the organic phase is collected, dried and concentrated under reduced pressure, this extract is dissolved in ethyl acetate and washed with water,
- the organic phase is evaporated under reduced pressure and the residue obtained is eluted with ethyl acetate through a silica column.
4.7 As the respondent argued, although the liquid-liquid separation and chromatographic techniques with a silica column are known and conventional in themselves, the specific solvent systems used and the order of the steps claimed to isolate SkE cannot be considered routine. More specifically, the definition of the exact conditions for each step and the sequence and chronological order of use of these steps to achieve the isolation of SkE, an unknown molecule, from a complex mixture, and to identify its activity can only be discovered on the basis of a long series of experiments and failures. As indicated by the respondent, to isolate SkE, it was necessary to use bioguided fractionation, which implies, according to the biological results, appropriate experimental techniques and conditions at each step of the isolation. It is therefore unjustified to conclude that the isolation defined in the patent could be done routinely. It is therefore not credible that the person skilled in the art, by implementing conventional separation procedures, would inevitably have come across the SkE molecule, as the applicants claim.
4.8 As indicated above, the applicants referred to Annex 2 to show that the SkE molecule had been found in a simple aqueous decoction/infusion of Quassia amara (Annex 2, first page, "Procedure"), that there were few different compounds present in the decoction, and that the SkE molecule was present in significant quantities. Using high-resolution mass spectrometry, the mass of the molecular ion [M+H]+ obtained at m/z 579.2816 corresponded to that of SkE with the addition of one hydrogen atom, showing the presence of SkE in the extract analyzed. Thus, Annex 2 showed that the SkE molecule could have been found by the skilled person in an aqueous extract, and therefore that its isolation would have been routine for the skilled person.
4.9 The Board does not share this view. As argued by the respondent, Annex 2 submitted by the applicants shows, a posteriori, the existence of the SkE molecule in its natural environment in a mixture with other molecules, having already known the chemical structure and its spectrometric characteristics, since all this information was already described in the patent.
4.10 More specifically, the Appendix shows the identification, in a mixture, of the SkE molecule, the existence of which was not known before it was isolated, identified, characterized and its activity demonstrated by the Respondent. Without the spectrometric data disclosed in the patent and in the 2014 publication cited in Appendix 2 (page 2, last paragraph), the skilled person would not have been able to know whether SkE was present in the mixture and what its formula and structure were.
4.11 Furthermore, as noted by the Respondent, none of the three chromatograms (ultra-high performance liquid phase - Appendix 2, page 2, second paragraph) of the infusion analyzed in Appendix 2 in BPI mode (Base Peak Intensity) which detect a mass range between m/z 50 and 1200, allow the detection of SkE because none of the three chromatograms shows a peak at 6 minutes corresponding to SkE (Appendix 2, fifth page). To identify SkE, it was necessary to work in SIM mode (Single Ion Monitoring), to be able to detect the peak corresponding to SkE at a retention time of 6 minutes (Appendix 2, sixth page). As the respondent explained, this peak and thus the SkE molecule were clearly identifiable in the chromatogram only because the mass detector had been programmed to see only it. This therefore shows that without the information included inter alia in the patent, there is no reason to conclude that the author of Annex 2 would have identified SkE in the tested extract.
4.12 Therefore, the steps taken by the author of Annex 2 do not correspond to the situation of the person skilled in the art before the priority date of the patent, only the latter being relevant for the assessment of inventive step. Therefore, the fact that SkE was identified in the tests of Annex 2 does not make it credible that the person skilled in the art, by implementing conventional separation procedures, would inevitably have come across the SkE molecule.
4.13 The applicants also argued that there was no inventive step where there was a reasonable expectation of success in view of the prior art documents. In the present case, the skilled person would have followed the teaching of document D43, including an incentive to search for the active components of Quassia amara leaves, and would have used the usual techniques of extraction and isolation of compounds in order to isolate and identify the active compounds with a reasonable expectation of success.
4.14 The Board does not agree. As argued by the respondent, there is no incentive in D43 or in the other documents, in particular D5 cited by the applicants, that could predict the SkE compound to be isolated from many other compounds existing in the plant Quassia amara, and the activity and toxicity of said compound. Indeed, as indicated by the respondent, the use of dry and mature leaves (used to isolate SkE according to the patent) is discouraged in D5 by the identification of these leaves as being the least active against Plasmodium falciparum ("...activity would have been denied to DM extract"; page 41, right column, "Results and discussion"). There is no incentive in D43, D4, D5 or in the other documents that the skilled person would have established the order and sequence of the different techniques and steps necessary to isolate the SkE molecule. Therefore, there is no reason to conclude that the person skilled in the art, based on document D43 and wishing to solve the above-mentioned objective technical problem, would have had a reasonable hope of success.
4.15 The applicants also submitted that even if the skilled person had no particular hope of success, given the motivation in D43 to search for active components of the plant Quassia amara, he would have at least attempted a "try and see" approach. Therefore, by implementing the usual extraction and isolation techniques, the skilled person would have had no difficulty in isolating the SkE molecule.
4.16 The Board disagrees at least for the reason that, as indicated above, the steps necessary to arrive at the SkE molecule are not considered routine or usual.
4.17 Therefore, the subject-matter of claim 1 involves an inventive step. The same conclusion applies to claims 2 to 6, which depend on claim 1 and relate to a medicament comprising the SkE molecule, and to claims 7 and 8 which relate to the process for isolating SkE. The ground for opposition of Article 100(a) EPC in conjunction with Article 56 EPC therefore does not preclude the maintenance of the patent as granted.
4.18 No grounds for opposition have been raised which would prevent the patent from being maintained, the appeal must be dismissed.
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