Biotechnology Law ReportVol. 40, No. 3 Original ArticlesFree AccessThe EPO Guidelines They Are a-Changin’By DR. Benjamin Quest and DR. Markus GrammelBy DR. Benjamin QuestDr. Markus Grammel is a German and European patent attorney at Grünecker in Munich, Germany. E-mail for Dr. Grammel: E-mail Address: grammel@grunecker.deSearch for more papers by this author and DR. Markus GrammelDr. Benjamin Quest is a European patent attorney at Grünecker in Munich. E-mail for Dr. Quest: E-mail Address: quest@grunecker.deSearch for more papers by this authorPublished Online:7 Jun 2021https://doi.org/10.1089/blr.2021.29236.mgAboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail In the European Patent Office (EPO), examiners and formalities officers in general follow the Guidelines for Examination in the EPO1 (the Guidelines). According to the EPO, the Guidelines “give instructions on the practice and procedure to be followed in the various aspects of the examination of European applications and patents in accordance with the European Patent Convention and its Implementing Regulations.”2 The Guidelines are internal administrative instructions that are adopted by the President of the EPO in accordance with the powers provided by Article 10(2)(a) of the European Patent Convention (EPC).3American practitioners will know the Manual of Patent Examining Procedure (MPEP). The EPO Guidelines are very much the European counterpart of this document.The Guidelines do not constitute legal provisions. Therefore, in principle, if a European patent application complies with the requirements of the EPC, but contravenes certain aspects of the Guidelines, this fact, in itself, does not prejudice the allowability of the application. For the ultimate authority on the practice in the EPO, the EPC itself and the Board of Appeal's4 interpretation of the EPC has to be observed—this is even pointed out by the Guidelines (General Part, 3). The Boards of Appeal have confirmed that the departments of first instance have the discretion to deviate from the Guidelines if this is required to act in accordance with the EPC. However, experience teaches that normally, the departments of first instance in the EPO, in particular the Examining Divisions and the Opposition Divisions,5 follow the Guidelines and are very reluctant to openly deviate from the Guidelines.The Guidelines are amended annually to reflect changes in the law and in the judicial practice of the Boards of Appeal. Naturally, as the Guidelines change, the practice at the EPO changes as well. The most recent revision has brought about a number of substantial changes that need considering by practitioners and applicants alike, with a number of changes being particularly relevant or even specific for biotechnological inventions.This article reviews these recent changes and their relevance for applicants and patentees in the biotech area.EXCEPTIONS TO PATENTABILITYDespite the general patentability of biotechnological inventions, the EPC specifically bars certain biotechnological subject matter from patent protection. In particular, the EPC excludes essentially biological processes for the production of plants or animals and plants or animals exclusively obtained by means of an essentially biological process (Article 53(a) EPC and Rule 28(2) EPC) and uses of human embryos for industrial or commercial purposes (Article 53(a) in combination with Rule 28(1)(c) EPC) from patentability.Over the past couple of years, the interpretation of these exclusion clauses has been the subject of a number of high-profile appeal cases.6 The resulting case law and practice is now reflected in the Guidelines.A claim directed to a product that at the filing date of the application could only be obtained by a method which necessarily involved the destruction of human embryos (e.g., isolation of stem cells from a human blastocyst that destroys the blastocyst) is excluded from patentability under Rule 28(1)(c) EPC. If at the filing date the product could be obtained without requiring the destruction of human embryos, the product is not excluded. The Guidelines now clarify that pluripotent human stem cells, including human embryonic stem cells, the use of such stem cells, or products derived therefrom, are not excluded under Article 53(a) and Rule 28(1)(c) if the application has a filing or priority date on or after June 5, 2003, and if the technical teaching of the invention allows the use of parthenogenetically activated human oocytes.7In decision G 3/19, the Enlarged Board of Appeal decided that Article 53(b) EPC precludes the patentability of product claims and product-by-process claims directed to plants, plant material, or animals, if the claimed product is exclusively obtained by means of an essentially biological process. The Enlarged Board essentially confirmed Rule 28(2) EPC, which had been added to the Implementing Regulations earlier by the Administrative Council, largely driven by political developments in Europe. The Guidelines8 now reflect the cut-off date of July 1, 2017, that had been defined by the Enlarged Board in G 3/19. Accordingly, the exclusion from patentability of essentially biological processes for the production of plants does not have a negative effect on the allowability of a product claim directed to plants or plant material, such as fruit seeds or other plant propagation material parts, if the application or the patent has a filing date or priority date that falls before July 1, 2017. Patents and applications with an earlier relevant date will not be negatively affected by Rule 28(2) EPC, whereas applicants for later applications have to ensure that the claimed product cannot only be obtained by an essentially biological process based on the sexual crossing of whole genomes and on the subsequent selection of plants or animals.PATENTABILITY OF ANTIBODIESGiven the ever-increasing relevance of antibody-based pharmaceuticals, it does not come as a surprise that antibody applications make up a large fraction of the biotech applications in the EPO. In general, antibodies as such can be patented in the EPO, i.e., product protection is available. There is no product-of-nature doctrine or statutory exclusion that constitutes a general bar to patentability for antibody claims. Quite to the contrary, Rule 27 EPC even explicitly states that biotechnological inventions shall be patentable if they concern “biological material which is isolated from its natural environment or produced by means of a technical process even if it previously occurred in nature” or products obtained by a microbiological process. As regards the clarity, sufficiency, and inventive steps requirements, antibody inventions are in principle not treated any differently than other types of inventions. However, the Boards of Appeal and the departments of first instance over the years have developed standardized approaches to assess antibody claims. With the most recent revision of the Guidelines, many of these standards have now been added to the Guidelines.9The new section of the Guidelines provides detailed guidance on how antibody claims may be drafted.10 The Guidelines exemplarily mention that traditional antibodies, consisting of two heavy chains and two light chains, as well as variants of antibodies, such as antibody fragments, bispecific or multi-specific antibodies, and antibody fusion products, can be defined by their structure (amino acid sequences), the nucleic acid sequences encoding the antibody, by reference to the target antigen (with or without further functional features), a combination of functional and structural features, the production process, the epitope, or the hybridoma producing the antibody.Conventional antibodies consist of two identical heavy chains, each comprising three complementarity defining regions (CDRs), and two identical light chains, each comprising three additional CDRs. The three CDRs of a light chain and the three CDRs of a heavy chain make up the “paratope,” which is the antigen-binding side of the antibody that recognizes a corresponding “epitope” of the antigen. It is therefore generally accepted that antibody-antigen binding specificity is predominantly determined by the CDRs of the antibody (even though other regions of the antibody, such as the “framework regions” may also influence binding).In line with this technical understanding, the new Guidelines require that a claim recites all six CDRs, either by sequence or by a generally accepted numbering scheme, such as Kabat, Chothia, or IMGT, if the antibody is exclusively defined by its structure. If a conventional antibody, i.e., an antibody that typically comprises six CDRs, is defined by less than six CDRs, the claim is considered to lack an essential technical feature. In such a case, the requirements of Article 84 EPC are considered to be fulfilled only if it is experimentally shown that one or more of the six CDRs are dispensable for epitope recognition. Such experimental data should be included in the application at the filing date.In principle, according to the Guidelines, antibodies can also be defined by the target antigen, e.g., “antibody binding to X.” However, the fact that the identification of novel protein targets has become rare also makes this claim type a rare event. Typically, current antibody claims require additional technical features, other than antigen identity, to overcome the novelty and/or inventive step hurdle.Most of the talk about antibody claims in the EPO concerns the two extremes of the spectrum of antibody claim types. On the one end of the spectrum, there are very broad, exclusively functionally defined antibody claims, which may pose problems for competing originators that work on the same target as well as generics. On the other end of the spectrum, given the EPO's inventive step standard for antibody inventions (see below), it may be even challenging to obtain protection for a very narrow, picture-type claim for a specific antibody. The new Guidelines show that under specific circumstances, the EPO still grants broad functional antibody claims.Functional features that are exemplified in the Guidelines for defining an antibody are binding affinity, neutralizing properties, induction of apoptosis, internalization of receptors, and inhibition or activation of receptors. In principle, an antibody may be exclusively defined by such functional features. However, the Guidelines note that functional limitations will suffer from an inherent lack of novelty if the prior art discloses raising antibodies against the same antigen, using an immunization and screening protocol that arrives at antibodies having the recited functional properties. In this context, the Guidelines also refer to the novelty standard concerning “unusual parameters” and state that the burden of proof for novelty in these cases rests with the applicant. Accordingly, the applicant should be prepared to demonstrate by evidence that the recited functional features in fact distinguish the claimed antibody from the antibodies of the prior art.The combination of structural and functional features is explicitly mentioned in the Guidelines as one option to claim an antibody. If a clear functional feature is included in the claim, claiming variable domain or CDR sequences with less than 100% sequence identity is possible. Accordingly, the Guidelines recognize the general practice that a broader structural scope of an antibody claim may be compensated with functional technical features. This is particularly the case if the functional feature represents the technical effect on which the inventive step of the antibody is based, e.g., a specific binding affinity.The Guidelines also discuss the requirements for an inventive step in the case of antibody inventions.11 The section on inventive step emphasizes two key aspects when considering the inventive step requirement12 for antibody inventions.First, the Guidelines state “a novel, further antibody binding to a known antigen does not involve an inventive step unless a surprising technical effect is shown by the application,” referring to seminal decision T 735/00. In this decision, the competent Board of Appeal held that the provision of a monoclonal antibody by routine methods only involves an inventive step if the antibody shows unexpected properties. Accordingly, preparing a novel antibody to a known target typically only involves an inventive step if the antibody is associated with an unexpected, surprising technical effect.Second, the Guidelines confirm the practice that the EPO does not recognize structural non-obviousness-type arguments for an inventive step of antibodies. The mere fact that the prior art does not suggest the specific antibody sequence is not sufficient for an inventive step. Therefore, even in cases where the claim recites the entire novel antibody amino acid sequence, heavy and light chain, the application demonstrates binding to the antigen, potentially a pharmaceutical effect, and there is no pointer in the prior art to the specific sequence, this may not be enough for an inventive step to be recognized by the EPO.The name of the game is surprising technical effect—to increase the likelihood of taking the hurdle of inventive step, data should be included in the application that demonstrates unexpected improvements over prior art antibodies or particular advantages associated with the claimed antibodies (ideally in the form of comparative data). Alternatively, it may involve an inventive step if certain technical difficulties had to be overcome when producing the claimed antibodies.To summarize, the Guidelines now reflect for the first time the relatively strict approach of the EPO with respect to antibody claims, embodied in particular by the EPO's rejection of structural non-obviousness.UNITY OF INVENTIONOne section of the Guidelines that is particularly relevant for biotechnological inventions that has been widely revised is the section on unity of invention, F-V. Given that the EPO's approach to unity of invention differs significantly from the approach of the U.S. Patent and Trademark Office (USPTO), it is worthwhile to generally consider the approach of the EPO first in more detail. These different approaches to unity of the two offices are often revealed during the international phase of Patent Cooperation Treaty (PCT) applications, even though the different offices should apply the same standard following the PCT Guidelines.13 While the EPO's approach is very close to the approach adopted for PCT proceedings (i.e., a unifying special technical feature concept), the USPTO's approach is rather different. Before the USPTO, national applications are assessed according to the “independent and distinct” standard (requiring a group and species election) and this standard regularly bleeds into PCT stage unity assessments (although it should not). The key differences between the USPTO and the EPO are that the USPTO will require the applicant to restrict their claims to an elected group/species and perform a top-up search on the elected subject matter afterwards, while the EPO will stop the search and send out a Communication giving the applicant the opportunity to pay additional search fees for each invention identified by the EPO. The applicant will then be required during substantive examination to restrict the claims to a searched invention. However, practically, it is often possible to amend the EP claims during examination to include more than one searched invention as long as the new claims are then unified by a common special technical feature.Notably, the five big IP offices (EPO, USPTO, China National Intellectual Property Administration [CNIPA], JPO [Japan Patent Office], and KIPO [Korean Intellectual Property Office]) are working towards harmonization of the unity assessment, resulting in a minimum non-unity reasoning14 that was proposed at the end of 2018 for implementation. Therefore, hopefully, unity assessments of the different offices during the PCT stage will see some harmonization in the future. In fact, the majority of changes that went into the Guidelines section that relate to unity of invention implements the minimum requirements for reasoning of lack of unity based on the IP5 harmonization initiative.Prior artOne difference that the new Guidelines make over the old version is that they further specify the term “prior art at hand.”15 It is clarified that the “prior art at hand” may vary depending on the stage of the proceedings. The Guidelines state explicitly “the assessment of unity is iterative.” Accordingly, it seems likely that we will see more unity objections in later stages of the proceedings than before, where unity objections were usually confined to the search stage and were very rare in substantive examination.Unity assessmentThe prior substantive unity assessment in the Guidelines was a two-tier process of (1) determining the subject-matter that is common to the claims directed to the different claimed inventions, i.e., the technical features of the different inventions that are the same and/or corresponding; and (2) examining whether any of this common matter is special within the meaning of Rule 44(1) EPC (i.e., is prima facie novel and inventive and thus makes a contribution over the prior art; also referred to as “single general inventive concept”).This two-tiered assessment has now been replaced with a three-tiered approach (explained in detail in section F-V, 3 of the Guidelines) of (1) determining the common matter, if any, between the claims of the different claimed inventions; (2) comparing the common matter with the “prior art at hand” to examine whether the common matter makes a contribution over that prior art, namely, whether it comprises “special” technical features within the meaning of Rule 44(1) EPC; and (3) if the common matter does not comprise special technical features, analyzing any remaining technical features which are not part of the identified common matter to determine if there is a unifying technical relationship among some of the claims.It is the last step of the three-tiered approach that will likely lead to a change in practice. This step requires examiners to not stop the assessment at the level of shared technical features (common matter). Now, examiners are required to search for alternative unifying matter, before raising a unity objection. The last step of analyzing the remaining technical features is now also a structured approach that aims to group inventions by the technical problems that they are associated with, which requires the examiners to also take into account the effects that are associated with the recited features. For the grouping it is now irrelevant whether the remaining technical features are novel over the prior art at hand, which will hopefully avoid the kind of “nested” unity objections (further subdividing already identified subdivisions). The more-structured approach of the new Guidelines will hopefully lead to more a reasonable grouping of inventions than before.We may not necessarily see fewer unity objections, but we may at least expect objections where the number of inventions do no longer go overboard, as regularly seen in the biotechnological field.16The grouping of inventionsAs regards a plurality of independent claims of different categories, the Guidelines no longer regard certain combinations of claims (product + method of producing the product + use of the product) to be unitary “by definition.”17 This may give rise to the possibility that if the product claim in the example above is not new, the independent claims may now become separated into different inventions.Unity reasoningAnother prominent change is the implementation of minimum requirements for reasoning a lack of unity18 in line with the IP5 initiative. This “minimal reasoning” is minimal in name only, as it requires the EPO to produce a very detailed and structured reasoning concerning all points discussed so far. The common matter needs to be identified, reasons need be given why the common matter does not convey unity in view of the prior art at hand, and detailed reasons on any further grouping based on the remaining technical features of claim groups need to be discussed by the EPO. Notably, the EPO has to reason, e.g., why grouped alternative chemical compounds are not of a similar nature. This mandatory “minimum reasoning” is, in our view, a welcomed addition to the Guidelines as it ensures a structured approach and a more transparent reasoning.The largely revised section F-V of the new Guidelines suggests that we will not necessarily see fewer unity objections (as the “prior art at hand”–approach may invite unity objections in advanced stages of the examination), but better reasoned ones. “Better reasoned” in this case means that the structured approach may reduce the overall number of identified inventions, in particular in the biotechnological field, and that any non-unity objection will now be accompanied with a (hopefully) well-structured and comprehensive reasoning. A reduced number of individual inventions would also reduce the amount of additional search fees required to have all inventions searched, in case of a non-unity objection at the search stage.BIOLOGICAL DEPOSITSThe new Guidelines now strongly advise applicants to file copies of the deposit receipt(s), which are issued by the depository institution, since the deposit receipt shows the information required under Rule 31 EPC and also identifies the depositor, thus enabling the EPO to establish whether the application satisfies the requirements under Article 83 EPC (sufficiency of disclosure). Filing the deposit receipt is also an essential requirement for identifying the depositor, whose name needs to be established, before the EPO may certify a third party's request for the issuance of a sample of the deposited material. The new Guidelines now also adopt a new section, A-IV, 4.4, regarding how requests for samples of biological material are to be dealt with. However, no change in practice is associated with the additions in section A-IV of the Guidelines, since they were previously part of the ancillary regulations.19SEQUENCE LISTINGSOne notable change regarding the late furnishing of sequence listings (SL) occurred in section A-IV, 5 of the Guidelines. The EPO considers the late furnishing fee to compensate for the administrative efforts of issuing the communication under Rule 30(3) and delaying the transmission of the application to the search division until after availability of a World Intellectual Property Organization (WIPO) standard ST.25-compliant SL. Therefore, the late furnishing fee does not have to be paid if the WIPO standard ST.25-compliant SL is filed after the date of filing, but before the Receiving Section has issued the communication under Rule 30(3). If applicants note deficiencies in the SL, acting quickly now pays off (worth 240 EUR).SEQUENCE HOMOLOGYA new section in the Guidelines, F-IV, 4.24, now clarifies the EPO's approach of how to calculate sequence identity. The percentage of identity determines the number of identical residues over a defined length in a given alignment. If no algorithm or calculation method for determining the percentage of identity is defined, the broadest interpretation will be applied using any reasonable algorithm or calculation method known at the relevant filing date. For protein sequences defined in terms of “similarity,” the EPO considers that if no similarity-scoring matrix is defined, a claim referring to a sequence displaying a percentage of similarity to a recited sequence is considered to cover any sequence fulfilling the similarity requirement as determined with any reasonable similarity-scoring matrix known at the relevant filing date. For amino acid sequences, if a percentage of homology is used by the applicant as the only feature to distinguish the subject matter of a claim from the prior art, its use is objected to under Art. 84 EPC (lack of clarity), akin to relative terms like “thin” or “broad,” unless the determination or calculation of the percentage of homology is clearly defined in the application as filed. For nucleic acid sequences, the EPO regards the terms “homology percentage” and “identity percentage” to have the same meaning.This seems to be a change of the practice towards a stricter requirement for biological sequence definitions. That is, if no algorithm for homology/similarity is part of the application, the claims will be construed broadly, possibly attracting novelty objections. Applicants are therefore advised to prepare new filings to contain or refer to the algorithms used for determining sequence homology/similarity in order to avoid overly broad interpretation or lack of clarity objections.SECOND MEDICAL USE CLAIMSConcerning second medical use claims (in the EPO formulated as purpose-limited product claims: “substance X for use in the treatment of disease Y”), the new Guidelines implement, in section G-II, 4.2.1.2, the holding in decision T 385/09 of the Boards of Appeal. The Guidelines clarify that preventing a pathological state is regarded as therapy, but the treatment of a healthy subject (which is not likely to develop a pathological state) to avoid discomfort or to provide relief from discomfort does not constitute a therapy. Applicants in the field of, e.g., nutraceuticals or food products with health claims may be advised to phrase their claims accordingly (e.g., to draft use or method claims).With respect to products that may be claimed for a further medical use in the form of purpose-limited product claims (Art. 54(5) EPC compliant claims), the new Guidelines also provide some more detail.20 A product qualifies as a “substance or composition” in the sense of Art. 54(5) EPC if it is the active agent or ingredient in the specific medical use and if the therapeutic effect can be ascribed to its chemical properties. The Guidelines refer to decision T 1758/15, in which the Board clarified that if a material exerts a therapeutic effect due to its mechanical properties, it qualifies as a “device” and not as a “substance or composition” and is therefore not amendable to second medical use protection. The standing practice of the EPO is not changed by this clarification of the Guidelines; however, applicants are reminded that products that do not exert a therapeutic effect on their own due to their chemical properties are not eligible for second medical use claim protection. Accordingly, for applications directed to scaffolds, sustained release material, fillers, etc., attention should be paid that the claims relate to the therapeutic agent(s) as such and that the claim specifies the mode of administration, to include the scaffold/filler/etc., that is used in the composition. For example, if the invention is to a new scaffold material S that improves the therapy with the drug X, a proper claim would read: Substance X for use in a method of treating disease A, wherein X is administered in the form of a composition comprising scaffold material S.CONCLUSIONThe Guidelines are continuously updated by the EPO, and more recently, the EPO even has invited practitioners and the public to provide their comments on the Guidelines to contribute to what is hopefully a steady improvement of the Guidelines. In fact, the new section on the patentability of antibodies and unity of invention derive to a substantial degree from repeated requests by users to update the Guidelines accordingly. Overall, the Guidelines properly reflect the developing case law on the provisions of the EPC. In the same way as the written law (e.g., Rule 28(2) EPC) and the jurisprudence of the Boards of Appeal develop over time, the Guidelines develop as well. With the last update, the Guidelines have seen a major overhaul as regards the patentability of antibody inventions and the assessment of unity of invention. Examiners and practitioners alike as well as applicants and patentees have to adapt constantly to the developing situation to ensure that the EPO grants strong and valid patents. In this spirit, we close with Bob Dylan's famous lyrics “And you better start swimmin’ Or you'll sink like a stone.”1 European Patent Office (EPO), Guidelines for Examination in the European Patent Office, https://www.epo.org/law-practice/legal-texts/guidelines.html [hereinafter Guidelines].2 Id.3 European Patent Convention (EPC) as in force since December 13, 2007.4 The Boards of Appeal and the Enlarged Board of Appeal are the first and last judicial review instance within the EPO, which are vested with the authority to review and, if necessary, set aside the decisions of the EPO's departments of first instance.5 Substantive patent examination in the EPO is carried out by the Examining Divisions, consisting of three examiners, and post-grant opposition proceedings are conducted by Opposition Divisions, also typically consisting of three examiners.6 See decisions G 2/12, G2/13, and G 3/19 on essentially biological processes and plants and animals exclusively obtained by such a process; see G 2/06 and T 2221/10 on human embryonic stem cells and uses of human embryos.7 Guidelines, G-II, 5.3.8 Guidelines, G-II, 5.4.9 See Guidelines, G-II, 5.6.10 See Guidelines, G-II, 5.6.1.11 Guidelines, G-II, 5.6.2.12 Article 56 EPC.13 Patent Cooperation Treaty (PCT) International Search and Preliminary Examination Guidelines, Part III, ch. 10.14 European Patent Office, Unity of Invention—Proposal for a Non-Unity Minimum Reasoning (Nov. 15, 2018), available at Unity of Invention, Five IP Offices, https://www.fiveipoffices.org/activities/harmonisation/unity+of+invention (see link to “methodology”).15 Guidelines, F-V, 2, 3.16 See, e.g., PCT/US2018/035597 where the EPO identified 451 individual inventions.17 Previous Guidelines, F-V, 2.2.1.18 Guidelines, F-V, 3.3.1.19 OJ EPO 2010, 498; OJ EPO 2017, A60; and OJ EPO 2017, A61.20 Guidelines, G-VI, 7.1.1.FiguresReferencesRelatedDetails Volume 40Issue 3Jun 2021 InformationCopyright 2021, Mary Ann Liebert, Inc., publishersTo cite this article:By DR. Benjamin Quest and DR. Markus Grammel.Biotechnology Law Report.Jun 2021.184-190.http://doi.org/10.1089/blr.2021.29236.mgPublished in Volume: 40 Issue 3: June 7, 2021KeywordsEuropean Patent OfficeGuidelinesBiotechnologyPatentsPDF download
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