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Sanofi-Aventis Deutschland GmbH, Sanofi Winthrop Industrie S.A., Sanofi-Aventis Groupe v. Amgen, Inc.
ACT_459505/2023
Munich (DE) Central Division - Section
Revocation Action
EN
EP3666797B1
Action n°: UPC 1/2023
Revocation action
Central division (Section Munich) delivered on 16 July 2024 concerning EP 3 666 797 B1
HEADNOTES:
in the prior art and/or (would) have been pursued by others. The decisive question that has to be answered is whether the claimed solution is non-obvious.
KEYWORDS: Revocation, claim interpretation, priority, inventive step, starting point, obviousness, inventive contribution, arbitrary selection out of several possibilities
represented by Agathe Michel-de Cazotte, Daniel Wise (Carpmaels & Ransford)
also at the hearing by: Emily Nikolić (Carpmaels & Ransford) and Gregor König (König Szynka - Tilmann - Von Renesse).
Amgen, Inc. , One Amgen Center Drive - CA 91320-1799 - Thousand Oaks - US
represented by Koen Bijvank (Brinkhof)
also at the hearing by: Daan de Lange, Rik Lambers, Jonathan Santman, Roza Rijpkema (Brinkhof), Johannes Heselberger and Axel Berger (Bardehle Pagenberg) and H. Ulrich Dörries (df-mp).
European patent EP 3 666 797 B1, hereafter referred to as ' EP 797 ' or as 'the Patent'.
Panel 1 of the Central Division (Munich Section)
This decision has been delivered by the presiding judge Ulrike Voß, the legally qualified judge András Kupecz as judge-rapporteur and the technically qualified judge Casper Struve.
February 2024 (ORD_392/2024), the Local Division Munich, with the agreement of the parties, referred the Counterclaim of Regeneron to the Central Division.
1 The Statement of Revocation, Defence to Revocation, Reply to the Defence to Revocation and
Rejoinder to the Reply to the Defence to Revocation in case 459505/2023 are herein referred to as ´. The parties each made a further
´ SR ´, ´ DtR ´, ´ RtD ´ and ´ R ´, respectively. The counterclaim for revocation in CC_586764/2023 is referred to as ´ CC ´ and the Defence to the Counterclaim as ´ DtCC submission in CC_586764/2023, referred to as ´ RtDCC ´ and ´ RCC ´, respectively.
published as WO2009/026558 (A1), and entered the European regional phase as EP Application No. 08798550.3 (granted as EP 2 215 124).
treating or preventing hypercholesterolemia or an atherosclerotic disease related to elevated serum cholesterol levels;
or for use in reducing the risk of a recurrent cardiovascular event related to elevated serum cholesterol levels;
wherein the monoclonal antibody or the antigen-binding fragment thereof binds to the catalytic domain of a PCSK9 protein of the amino acid sequence of SEQ ID NO: 1, and prevents or reduces the binding of PCSK9 to LDLR.
ischaemic or hemorrhagic stroke, angina pectoris, cerebrovascular disease, acute coronary syndrome, or myocardial infarction.
and:
-dismisses the Defendant's Application to amend the Patent, as the amendments are not allowable and the Patent in suit cannot be maintained as requested in Auxiliary Requests (AR) 1-17.
3.3 The Defendant has put forward various defences including a (conditional) application to amend the Patent which was lodged together with the Defence to Revocation.
3.4 Defendant requests (as clarified during the oral hearing) that:
-the Revocation Action be rejected as being unfounded and the Patent be maintained as granted (Main Request; or 'MR');
or failing that
5.1 An antibody is a type of protein (also called an immunoglobulin, 'Ig') that is produced by the immune system in response to a foreign substance. Each antibody recognizes a particular target, also referred to as an 'antigen'. Like all proteins, antibodies are made up of amino acids. Each amino acid has distinct chemical and physical properties. The amino acid sequence of an antibody is a major factor affecting how the antibody protein will fold into a three-dimensional structure, which in turn helps to determine which antigen or antigens the protein can bind, and how the antibody functions.
5.2 Each antibody is made up of two pairs of identical polypeptide chains (chains of amino acids linked together by peptide bonds) that form a flexible Y shape. Each pair comprises a heavy chain polypeptide (the green segments depicted in the figure below) and a light chain polypeptide (the blue segments depicte d in the figure below) that are held together by disulfide bonds (' -SS' in the figure). Each polypeptide chain, light or heavy, has a 'constant' and a 'variable' domain. The ordering of amino acids in the heavy and light chain protein sequences of an antibody is encoded by the heavy and light chain genes for that antibody.
5.3 The variable domains are referred to as such because the amino acid sequence in these domains differs between antibodies. The variable domains make up the antigen-binding sites of an antibody, with each of the two antigen-binding sites within a particular antibody being identical.
5.4 The epitope is the region of an antigen that is bound by an antibody. When the antigen is a protein, the binding of an antibody to its antigen occurs via interactions between the amino acid residues on the antibody and the amino acid residues on the antigen.
5.5 As of the earliest priority date of the Patent in 2007, methods of making antibodies were well-established.
5.6 For example, antibodies can be made by immunizing mice. That involves immunizing mice with the desired target antigen, harvesting the mice, collecting the antibody-producing mouse B cells and fusing them with 'immortal' cells to create 'hybridomas.' Antibodies generated by the mouse immune system are then collected from the hybridomas for screening, each hybridoma cell producing a single antibody.
Figure 4 in the CC.
5.9 The Patent relates to antigen binding proteins that bind to proprotein convertase subtilisin kexin type 9 (´PCKS9´) and methods of using and making the antigen binding proteins.
5.10 As regards the background to the invention, the Patent initially states that PCSK9 is a serine protease involved in regulating the levels of the low density lipoprotein receptor (LDLR) protein (para. [0002]). LDLR is a protein receptor expressed on the surface of liver cells that is important for removing Low density lipoprotein cholesterol (LDL-C), which is transported by Low density lipoprotein (LDL) throughout the body. Typically, LDLRs on the cell surface bind to LDL-C, transport LDL-C into the cell where it is broken down for the use by the body, and are then recycled to the cell where they can continue transporting LDL-C from the bloodstream into the cell.
5.11 Still according to the background section of the Patent, in vitro experiments had shown that adding PCSK9 to HepG2 cells lowers the levels of cell surface LDLR. Experiments with mice had shown that increasing PCSK9 protein levels decreases levels of LDLR protein in the liver, while PCSK9k knockout mice have increased levels of LDLR in the liver. Additionally, various human PCSK9 mutations that result in either increased or decreased levels of plasma LDL had been identified. PCSK9 had been shown to directly interact with the LDLR protein, be endocytosed along with the LDLR, and to co-immunofluoresce with the LDLR throughout the endosomal pathway.
5.12 Moreover, according to the background section of the Patent, it had been found that PCSK9 binds to the EGFa domain within the LDLR, referencing Zhang et al. , 2007 (submitted as C4 in these proceedings). As the Patent further states, degradation of the LDLR by PCSK9 had not been observed and the mechanism through which it lowers extracellular LDLR protein levels is uncertain. Selective inhibition of the PCSK9 gene in hyperlipidemic mice using an antisense oligonucleotide (ASO) resulted in significant reductions in hepatic PCSK9 mRNA levels, with concomitant reductions in total cholesterol and LDL (para. [0002]).
5.13 The Patent explains as further background that PCSK9 is a prohormoneproprotein convertase in the subtilisin (S8) family of serine proteases (para. [0003]). Prohormone-proprotein convertases are expressed as zymogens and they mature through a multistep process. Humans have nine prohormoneproprotein convertases. Crystal and NMR structures of different domains from mouse furin and PC1 revealed subtilisin-like pro- and catalytic domains, and a P domain directly C-terminal to the catalytic domain. Based on the amino acid sequence similarity within this subfamily, all seven members were predicted to have similar structures.
5.14 Prohormone-proprotein convertases are expressed as zymogens and they mature through a multi-step process. The function of the pro-domain in this process is two-fold. The pro-domain first acts as a chaperone and is required for proper folding of the catalytic domain. Once the catalytic domain is folded, autocatalysis occurs between the pro-domain and catalytic domain. Following this initial cleavage reaction, the pro-domain remains bound to the catalytic domain where it then acts as an inhibitor of catalytic activity. When conditions are correct, maturation proceeds with a second autocatalytic event at a site within the pro-domain. After this second cleavage event occurs the pro-domain and catalytic domain dissociate, giving rise to an active protease (para. [0004]).
5.15 Finally, the background section of the Patent explains that autocatalysis of the PCSK9 zymogen occurs between Gln152 and Ser153 (VFAQ|SIP), and had been shown to be required for its secretion from cells. A second autocatalytic event at a site within PCSK9's pro -domain had not been observed. Purified PCSK9 is made up of two species that can be separated by nonreducing SDSPAGE; the pro-domain at 17 Kd, and the catalytic plus C-terminal domains at 65 Kd. PCSK9 has not been isolated without its inhibitory pro-domain, and
measurements of PCSK9's cat alytic activity have been variable (para. [0005] of the Patent description).
F2.1 in treating or preventing hypercholesterolemia or an atherosclerotic disease related to elevated serum cholesterol levels;
or
F2.2 in reducing the risk of a recurrent cardiovascular event related to elevated serum cholesterol levels.
6.3 The Court of Appeal of the UPC has laid down the following legal framework for the interpretation of patent claims (Order dated 26 February 2024 in UPC_CoA_335/2023, NanoString/10x Genomics , p. 26-27 of the original German language version, also see CoA UPC 13 May 2024, VusionGroup/Hanshow ).
6.4 In accordance with Art. 69 EPC and the Protocol on its interpretation, a patent claim is not only the starting point, but the decisive basis for determining the scope of protection of a European patent. The interpretation of a patent claim does not depend solely on the strict, literal meaning of the wording used. Rather, the description and the drawings must always be used as explanatory aids for the interpretation of the patent claim and not only to resolve any ambiguities in the patent claim. However, this does not mean that the patent claim merely serves as a guideline and that its subject-matter also extends to what, after examination of the description and drawings, appears to be the subject-matter for which the patent proprietor seeks protection.
6.5 The patent claim is to be interpreted from the point of view of a person skilled in the art.
6.6 When interpreting a patent claim, the person skilled in the art does not apply a philological understanding, but determines the technical meaning of the terms used with the aid of the description and the drawings. A feature in a patent claim is always to be interpreted in light of the claim as a whole (CoA UPC 13 May 2024, VusionGroup/Hanshow , point 29). From the function of the individual features in the context of the patent claim as a whole, it must be deduced which technical function these features actually have individually and as a whole. The description and the drawings may show that the patent specification defines terms independently and, in this respect, may represent a patent´s own lexicon. Even if terms used in the patent deviate from general usage, it may therefore be that ultimately the meaning of the terms resulting from the patent specification is authoritative.
6.7 In applying these principles, the aim is to combine adequate protection for the patent proprietor with sufficient legal certainty for third parties.
6.8 As held by the Court of Appeal, these principles apply also to the assessment of validity. Accordingly, these principles will also be applied by the Central Division to claim construction in the context of the present revocation action. The relevant point in time for interpreting a patent claim for the assessment of validity is the filing (or priority) date of the application that led to the patent in suit.
methods of obtaining the antibody or antigen-binding fragment thereof. The description mentions multiple ways of obtaining antibodies. It was common general knowledge that antibodies can be produced using various methods. The skilled person therefore understands that the claim covers antibodies made using any such method. The antibody is (only) characterised in more detail by means of (functional) features F.3 and F.4 and its uses (F.2).
2 Individual amino acids are often denoted by thre e letter codes (such as 'Gln' for Glutamine, 'Ser' for serine) and their position in a sequence (e.g. 'Gln152'). Amino acids can also be denoted by a one letter code. For instance 'V' stand for valine, F for 'phenylalanine' etc.
description of the Patent, SEQ ID NO:3 corresponds to SEQ ID NO:1, whereby SEQ ID NO:1 lacks the signal sequence. Accordingly, in Figure 1A the underlining of the prodomain ends at Gln ('Q') 122 (cf. par. [0058] of the description). The skilled person thus understands from the description that the pro-domain of PCSK9 ends at Gln122 and, accordingly, that the catalytic domain of PCSK9 starts at Ser123 of human PCSK9 (SEQ ID NO: 1).
ordinary, technically sensible meaning, i.e. the antibody must bind to at least one amino acid residue that lies within the catalytic domain. The claim leaves open where the binding (to the catalytic domain) must take place. The claim does not further specify what 'binds to' means in qualitative nor in quantitative terms as long as the antibody 'binds'.
6.18 The claim is not limited to antibodies that bind exclusively (or even predominantly) to amino acid residues that lie within (in other words to antibodies that bind to an epitope that lies within) the catalytic domain. Antibodies that bind to the catalytic domain and also to the other (i.e. the pro or V-) domains of PCSK9 fulfil feature F.3.
6.19 The description of the Patent does not lead to a different (narrower) interpretation of feature F.3. Par [0036] mentions an antibody that ' binds to an epitope within residues 31-447 of SEQ ID NO: 3. ' However, in the same paragraph, it is said that in some instances the antibody ' binds to the catalytic domain '. The description also mentions other antibodies that bind to PCSK9 within a certain distance of particular amino acid residues (see e.g. par. [0037]). In addition, paragraphs [0400]-[0404] (Example 28) describe that the EGFa domain of LDLR binds to the catalytic domain of PCKS9. A crystal structure of PCKS9 bound to EGFa is shown and specific PCSK9 core interaction residues were defined. However, with regard to the binding site or location, the claim is not limited to the region where, according to the Patent's findings, binding between PCKS9 and LDRL actually takes place. Rather, the claim is formulated more broadly and specifies a larger region, the catalytic domain, as the region to which binding must take place.
6.20 A technical functional reason why the antibodies must bind to the catalytic domain is not provided by the Patent. It is clear from the description that the requirement of binding of the antibody to the catalytic domain of PCKS9 is unrelated to any (auto)catalytic function of PCKS9. There is furthermore no apparent causal technical connection between binding to the catalytic domain and the function of the antibody. Such a technical connection is also not explained by the section of the Patent description that discusses exemplary epitopes (par. [0235]-[0256] of the description). To the contrary, par. [0238] states that ' In some cases, antigen binding proteins disclosed herein bind specifically to N-terminal prodomain, a subtilisin like catalytic domain and/or a C-terminal domain '. No reason is given for the requirement of binding to the (subtilisin like) catalytic domain.
6.21 The skilled person furthermore derives from the description that while the binding site of PCSK9 and LDLR is located within the catalytic domain, the binding of PCSK9 and LDLR involves only particular amino acid residues that are part of a smaller area within the catalytic domain. This confirms that the LDLR binding site on PCSK9 and the catalytic domain of PCSK9 are not congruent. The catalytic domain is (significantly) larger than the part of PCSK9 that interacts with the (EGFa domain on) LDLR. The description indeed points out in par. [0420] that: ' it is clear that antigen binding proteins that bind to PCSK9 can also inhibit the interaction between PCSK9 and the LDLR by clashing with various regions of the LDLR (not just the site at which LDLR and PCSK9 interact)… ' and in some instances an antibody ' binds to PCSK9 at a position that is further away from [a location that overlaps with the interaction locations between PCSK9 and EFGa, Ab 31H4, and/or Ab 21B12] ' and ' can still be an effective neutralizing antigen binding molecule. ' (par. [0423]).
6.22 That it is not excluded that the antibodies (or fragments) claimed besides binding to the catalytic domain, additionally bind to a region outside the catalytic domain such as the pro-domain or the V-domain, is furthermore consistent with the description and the position of both parties, as exemplified by antibody 31H4 which, undisputedly, is an embodiment falling within the scope of the claims of the Patent, and which binds to the catalytic domain of PCSK9, but also makes contact with amino acid residues from the pro-domain (see Example 29).
6.23 However, feature F.3 should not be considered in isolation. Rather, its meaning must be determined in light of the claim as a whole and the underlying problem. In particular, features F.4 (and F.2) must also be considered. The skilled person recognises that the binding of the antibody required in F.3 is intended to have a consequence . Namely that which is mentioned in F.4: the antibody is intended to prevent or reduce the binding of PCKS9 to LDLR .
6.24 In the description it is explained that the antigen binding proteins can interfere with, block, reduce or modulate the interaction between PCSK9 and LDRL (par. [0421], [0426] of the Patent) and that the antigen binding proteins can bind to the catalytic domain in a manner such that PCSK9 cannot bind or bind as efficiently to LDLR (par. [0147], [0149] of the Patent). The binding according to feature 3 must therefore allow for this result to occur.
6.25 That it would be necessary for the binding to take place exclusively or primarily within the catalytic domain in order to fulfil this technical function is neither submitted by the parties nor otherwise apparent. To the contrary, as already discussed, antibody 31H4 binds to the catalytic domain of PCSK9, but also makes contact with amino acid residues from the pro-domain (see Example 29). The skilled person will therefore understand any binding which also takes place in the catalytic domain and which fulfils this technical purpose - preventing or reducing the binding of PCSK9 to LDLR - to suffice. In fact, the description also points out in par. [0424] of the Patent : ' As will be appreciated by one of skill in the art, when the antigen binding molecules are large enough, such as a full antibody, the antigen binding molecule need not directly bind to the EGFa binding site in order to interfere with the binding of EGFa to PCSK9. '
6.26 Consequently, the skilled person interprets the claims of the Patent as not being limited to antibodies that bind solely to amino acid residues within the catalytic domain, let alone to those amino acid residues (within the catalytic domain) that are directly involved in the interaction between PCSK9 and the EGFa domain of the LDLR. The skilled person will also bear in mind that the claims are not limited to any particular degree of reduction of the binding of PCSK9 to LDLR (as long as the antibodies are still suitable for the claimed medical use, see below feature F.2). Par. [0130] covers a very wide range of reducing percentages: ' …reduces the quantity of binding partner bound to the ligand by at least about 1-20, 20-30%, 30-40%, 40-50%, 50-60%, 60-70%, 70-80%, 80-85%, 85-90%, 90-95%, 95-97%, 97-98%, 98-99% or more (as measured in an in vitro competitive binding assay). '
6.27 The 'medical use features' F2.1 and F2.2 specify that the antibodies are for use in treating or preventing hypercholesterolemia or an atherosclerotic disease related to elevated serum cholesterol levels. Alternatively, the antibodies are for use in reducing the risk of a recurrent cardiovascular event related to elevated serum cholesterol levels.
6.28 The Defendant has argued that the skilled person would understand that, even though acknowledging that no complete cure is required, the claims are limited to ' therapeutically meaningful ' treatments (e.g. par. 48 SoDCC). Claimants on the other hand say that ' any lowering of an elevated cholesterol level fulfils the characteristics of the treatment of hypercholesterolaemia ' (CC, 124).
6.29 As mentioned above, F2.1 and F2.2 require that the antibody used must be objectively suitable for the claimed use(s). As such, the antibodies must be able to be used for the treatment, prevention or reduction specified in the claim. However, this does not say anything about the 'degree of effectiveness'. What is meant by the general terms 'treating' , 'preventing' or 'reducing the risk', in particular the degree to which this should be achieved, is not specified in the claim. The description gives a broad interpretation of treatment of hypercholesterolemia (see e.g. Example 20, ' reduced serum cholesterol levels in comparison to arthritis patients not receiving the treatment prevention '), as well as of the term 'prevention' see e.g. par. [0144] of the Patent : ' …the likelihood of the occurrence of the event has been reduced in the presence of the compound or method. '
6.30 In view of the teaching of the Patent as a whole, the skilled person would understand the claimed treatment not to be limited to a particular lowering of cholesterol levels as long as there is some (measurable) reduction of cholesterol levels in vivo and provided the therapy is safe. The Central Division furthermore notes that the claimed use encompasses the administration of the claimed antibodies together with at least one other cholesterol-lowering agent, notably statins (claims 6 and 7 of the Patent). This confirms the understanding of the skilled person that also a (very) small cholesterol-lowering effect caused by the claimed antibodies can be 'therapeutically effective' in the sense of the claimed treatments.
6.31 Based on the above interpretation, which combines an adequate protection for the patent proprietor with sufficient legal certainty for third parties, the Central Division accepts the position of the Defendant that not all antibodies that may conceivably bind to the catalytic domain are covered by the claim. By the same token, the skilled person will understand that antibodies that do not bind to the catalytic domain (but exclusively to the pro- or V-domain) are not covered by the claims. Thus, F.3, F.4 and F.2 indeed limit the number of antibodies falling under the claim. On the other hand, the claims are not limited to antibodies which , like 'reference antibodies' 21B12 and 31H4, are able to directly or sterically block PCSK9 from binding to LDLR by binding to or near residues that overlap with the EGFa binding region of PCSK9 (as suggested by Defendant, see e.g. 34 DtCC, also see above). For the skilled person, it will apparent that the patentee has chosen the present broader claim wording instead of defining the claimed antibodies in a narrower way.
7.5
In accordance with Article 87 EPC any person who has duly filed an application for a patent, a utility model or a utility certificate, or his successor in title, shall enjoy, for the purpose of filing a European patent application in respect of the same invention, a right of priority during a period of twelve months from the date of filing of the first application. This right can be
claimed in accordance with Article 88 EPC. The effect of a right of priority is that the priority date counts as the filing date of the European patent application for determining the state of the art (Article 89 in connection with 54(2) and (3) EPC).
7.7 Applying the above legal standard to the case at hand, the Central Division is of the opinion that the invention claimed in the Patent is disclosed in previous application P3 and that the Patent therefore validly claims priority of P3.
7.8 The skilled person derives from P3 that PCSK9 is a prohormone-proprotein convertase in the subtilisin (S8) family of serine proteases containing a prodomain, catalytic domain, and V-domain (or C-terminal domain) (e.g. par. [0003], [0004] P3). This is not disputed by the Claimants. From par. [0004], [0005], [0031]-[0032] in combination with Figs. 1A-1B in P3, the skilled person derives that the pro-domain means amino acids 31-152. A signal sequence is formed by amino acids 1-30 and is followed by the three domains. This is still not in dispute. Example 27, which describes a method for determining where various antibodies bind to PCSK9 (par. [0418]-[0419] in P3), discloses that the ProCat domain means amino acid residues 31-449 and V-domain means amino acid residues 450-692. This teaching is confirmed in par. [0431] of Example 30 (which shows that antibody 21B12 binds to the catalytic domain of PCSK9), par. [0453] of Example 34 and par. [0456] of Example 35 which all refer to residue 449 as the last residue of the catalytic domain. Example 33 in par. [0448] of P3 also mentions a PCSK9 ProCat together with a V-domain (450-692) sample. From this information, the skilled person will derive (directly and unambiguously) that the catalytic domain spans amino acids 153-449 (and that the V-domain starts at amino acid 450), corresponding to amino acids 123-419 in the numbering of SEQ ID NO: 1 without the signal sequence.
7.9 The fact that P3 in Example 33 also mentions a PCSK9 ProCat protein/variant consisting of amino acids 31-4 54 does not lead the skilled person to conclude that there is no (or at best an ambiguous) definition of the catalytic domain of PCSK9 in P3. This construct was generated for expression in bacoluvirus infected insect cells and subsequent purification, and was a construct that did not have a V-domain. In the case of the construct ' PCSK9 449TEV , a TEV ' protease cleavage site was, as brought forward by Defendant (44 SoD) and not (specifically) contested by Claimants, deliberately inserted between PCSK9 residues 449 and 450 to generate PCSK9 ProCat (31-449) and Vdomain samples. This confirms the skilled person´s understanding of the ProCat (and thereby also the 'Cat') domain ending at amino acid 449 (corresponding to residue 419 without the signal sequence).
7.10 The meaning of 'catalytic domain' as follows from P3 corresponds to how the skilled person interprets said term in the claims of the Patent as granted (see above, 6.12 et seq .).
7.11 Figure 26, which indeed has been added in P4 and which is also included in the Patent, is consistent with the above interpretation but does not contain any new information with respect to the amino acid sequence of the catalytic domain of PCSK9. Contrary to what the Claimants have argued, as also follows from the discussion under claim interpretation above, the skilled person does not see Figure 26 as the (sole) definition of the catalytic domain in P4 or the Patent. Rather Figure 26, whilst keeping consistent with the understanding of the pro-, catalytic and V-domains as follows from P3, shows a sequence comparison of the PCSK9 amino acid sequence ('PCSK9parent') and residues that were mutated in certain PCSK9 variants ('PCSK9mutants'). With respect to the definition of PCSK9´s catalytic domain, Figure 26 therefore does not add or change any technical information vis-à-vis the disclosure of P3 nor does it comprise the sole definition of 'catalytic domain' in the Patent (see above, 6.16 which reasoning applies mutatis mutandis here).
7.12 The mere fact that various prior art documents contain different definitions of which amino acid residues make up the catalytic domain of PCSK9, as pointed out by the Claimant, does not affect the skilled person´s understanding of the priority documents and the Patent. To the contrary, absent the existence of a commonly accepted state of the art definition of the catalytic domain of PCSK9 (the existence of which has not been brought forward by any of the parties), the skilled person will derive the meaning of 'catalytic domain' first and foremost from the priority and Patent documents themselves.
7.13 In conclusion, as the claimed subject matter is disclosed in P3, the arguments of the Claimants fail and the Patent can successfully claim priority from (at least) P3. Accordingly, the relevant date for assessing the contents of the prior art that will be used by the Central Division is 9 January 2008 .
8.5
8.6
8.7
8.8
It is only relevant what the claimed invention actually contributes to the prior art.
Inventive step is to be assessed from the point of view of the skilled person on the basis of the state of the art as a whole including the skilled person´s common general knowledge. The skilled person is assumed to have had access to the entire publicly available art on the relevant date. The decisive factor is whether the claimed subject matter follows from the prior art in such a way that the skilled person would have found it on the basis of their knowledge and skills, for example by obvious modifications of what was already known.
In order to assess whether or not a claimed invention was obvious to a skilled person, it is first necessary to determine a starting point in the state of the art. There has to be a justification as to why the skilled person would consider a particular part of the state of the art as a realistic starting point . A starting point is realistic if its teaching would have been of interest to a skilled person who, at the priority date of the patent at issue, was seeking to develop a similar product or method to that disclosed in the prior art which thus has a similar underlying problem as the claimed invention (cf. Court of Appeal Nanostring/10x Genomics , p. 34 under 'cc' in the German original version, ' Für eine Fachperson, die sich zum Prioritätszeitpunkt des Verfügungspatents vor die Aufgabe gestellt sah war […] D6 von Interesse' ) . There can be several realistic starting points. It is not necessary to identi fy the 'most promising' starting point.
Comparing the claimed subject matter, after interpretation following the guidelines provided above under 'claim interpretation', and the prior art, the subsequent question is whether it would be obvious for the skilled person to, starting from a realistic prior art disclosure, in view of the underlying problem, arrive at the claimed solution. If it was not obvious to arrive there, the claimed subject matter meets the requirements of Article 56 EPC.
In general, a claimed solution is obvious if, starting from the prior art, the skilled person would be motivated (i.e. have an incentive or in German: ' Veranlassung ', see the CoA in NanoString/10x Genomics , p. 34) to consider the claimed solution and to implement it as a next step (' nächster Schritt ', CoA in NanoString/10x Genomics , p. 35, second par.) in developing the prior art. On the other hand, it may be relevant whether the skilled person would have expected any particular difficulties in taking any next step(s). Depending
on the facts and circumstances of the case, it may be allowed to combine prior art disclosures.
Lagace (C3)
'The biological activity of PCSK9 was revealed through overexpression studies in mice. Overexpression of PCSK9 posttranscriptionally reduced the amount of LDLR protein in liver (3, 8 -10). Confirmation that PCSK9 functions normally to regulate LDLR protein levels came from loss-of-function studies in humans and mice.
Individuals who are heterozygous for a nonsense mutation in allele PCSK9 have significantly lower plasma LDL cholesterol levels, suggesting that a reduction in PCSK9 activity leads to an increase in LDLRs (11). These conclusions were supported by studies in PCSK9-knockout mice, which revealed that loss of PCSK9 resulted in increased numbers of LDLRs in hepatocytes, accelerated plasma LDL clearance, and significantly lower plasma cholesterol levels (12). In the most recent studies, humans heterozygous for loss-of-function mutations in PCSK9 were shown to have a significant reduction in the long-term risk of developing atherosclerotic heart disease (13)' (underline CD)
'The genetic data from humans and the in vivo studies in mice demonstrate that one function of PCSK9 is to reduce the number of the LDLRs and that this function is manifest in humans in the basal state. The mechanism by which PCSK9 reduces the number of LDLRs is still undetermined. For example, it is unclear whether PCSK9 acts to destroy LDLRs in the secretory pathway or whether it acts outside of the cell. In the current studies, we provide evidence that extracellular PCSK9 can be internalized by cultured liver cells and fibroblasts in a manner that is largely dependent on LDLRs. Incubation with extracellular PCSK9 led to loss of LDLRs .' (underl ine CD)
'The genetic data from humans with loss -of-function mutations in PCSK9 combined with the studies in knockout mice that lack PCSK9 clearly indicate that inhibitors of the protease would be of therapeutic benefit for the treatment of hypercholesterolemia. Inasmuch as overexpression of the catalytically inactive form of PCSK9 in mice did not alter LDLR protein levels (9), an inhibitor of PCSK9's protease activity in the ER should be sufficient to block its ability to reduce LDLR protein levels. If PCSK9 functions as a secreted factor as suggested by the current data, then additional approaches to neutralize its activity, including the development of antibodies to block its interaction with the LDLR or inhibitors to block its action in plasma, can be explored for the treatment of hypercholesterolemia .' (underline CD)
'These measurements demonstrate that considerable amounts of PCSK9 circulate in plasma and provided a range of physiologically relevant PCSK9 concentrations' (Lagace, p. 2996, lh col. second par.)
3 D374Y stands for a substitution of the amino acid aspartic acid (D) for the amino acid tyrosine (Y)
at position 374 in the amino acid sequence of PCSK9.
shows that the PCSK9 uptake in wild-type cells was high and was markedly reduced in the Ldlr-/- mice that did not produce LDLR. In Figure 4B and 4C it is shown by immunofluorescence staining of the cells that LDL-R and PCSK9 co-localize intracellularly in endocytic vesicles after uptake. According to the authors ' Considered together, the data … suggest that PCSK9 and LDL -R are taken up together into the cell and travel together to endosomes/lysosomes ' (Lagace, p. 2997, lh. col. last par.-p.2998 right col. first par.), which is a compartment in the cell that degrades proteins and explains the reduction in LDLR (175 CC, not disputed by the Defendant). Another experiment showed that PCSK9 still associated with cells in the absence of ARH (a protein that was known to be involved in LDLR internalisation, E2, par. 14). The experiment showed that ' internalization is required for PCSK9 to reduce the cell-surface expression of LDLR protein ' (Lagace, p. 2999, rh . col. first par.).
'As shown in Figure 7A, transgenic overexpression of human PCSK9 eliminated LDLR protein expression in liver and caused a marked increase in plasma LDL cholesterol levels (Figure 7B). The increase in plasma LDL cholesterol was similar to that measured in Ldlr - - mice that lacked LDLRs in all tissues.' /
Defendant´s arguments as to the speculative nature of the teaching of Lagace are to be discussed in the context of obviousness, but do not support the conclusion that the skilled person would not have been interested in Lagace at the relevant date.
'If PCSK9 functions as a secreted factor as suggested by the current data, then additional approaches to neutralize its activity, including the development of antibodies to block its interaction with the LDLR or inhibitors to block its action in plasma, can be explored for the treatment of hypercholesterolemia .' (underline CD)
Pursuing that route the skilled person would have ended up with antibodies as defined in the claims without inventive skill.
PCSK9 was a genetically validated target for lowering LDL levels in the blood
8.32 At the hearing, the Defendant disputed that at the relevant date PCSK9 was considered as a (genetically) 'validated' target for the treatment of hypercholesterolemia. Defendant argued that there was ' a possibility that PCSK9 might be a therapeutic target. ' In its Case Summary (par. 2), Defendant refers to PCSK9 as a ' potentially interesting therapeutic target '. The Defendant furthermore brought forward that PCSK9 antibodies were the first antibody treatment in the cardiovascular area of medicine.
8.33 According to the Central Division, even though there was no approved therapy at the relevant date targeting PCSK9 and the target may not have been a 'validated therapy' in that sense, the relevance of and significant (commercial) interest in PCSK9 as a target for the treatment of hypercholesterolemia had been well established and was generally accepted at the relevant date, in particular on the basis of the then available genetic data. This is confirmed in Lagace itself (see above, e.g. introduction and last paragraph of the Discussion) and is moreover corroborated by the fact that at the relevant date a considerable number of pharmaceutical companies were pursuing various (according to Defendant ' essentially all ', cf. oral hearing slide 27) options to target (inhibit) PCSK9. One of these companies was BMS, where Defendant´s expert Dr. was employed, who declares: ' As I explain above, the discovery of the gene encoding PCSK9 was made in 2003. The association of PCSK9 with hypercholesterolemia was a significant breakthrough. The possibility of reducing the prevalence of hypercholesterolemia and its established connection with ASCVD [atherosclerotic cardiovascular disease, CD] meant that there was significant value in targeting PCSK9. ' (E5, par. 203). This is also confirmed in the joint expert report of Dr. and Prof. prepared for Australian proceedings between the parties : ' We agree that the human genetic validation was very strong, and it was clearly desirable to seek a PCSK9 inhibitor to reduce LDL levels. The genetic validation of a drug target is rare and in this case was the reason multiple pharmaceutical companies had PCSK9 inhibition programs. ' (D95, 2.2). It is not in dispute that the relationship between elevated cholesterol levels and atherosclerosis was commonly known at the relevant date (see Dr. above, also 442 SoD).
8.34 There was accordingly a strong incentive at the relevant date for the skilled person to seek a PCSK9 inhibitor to reduce LDL levels in order to be able to treat hypercholesterolemia (and atherosclerotic diseases).
8.35 The skilled person faced with the task of finding a treatment for hypercholesterolemia targeting PCSK9 would according to Defendant not have pursued an antibody approach to targeting PCSK9, at least not with a reasonable expectation of success. Defendant gives the following reasons. First, the biological mechanism of PCSK9, in particular its site of action, were still unknown at the priority date. Second, it was not known which domains of PCSK9 interact with LDLR which would complicate an antibody approach. Besides these (fundamental) issues, there were further reasons why the skilled person would not have a had a reasonable expectation of success for an antibody approach. Given all of these unknowns, the skilled person would rather follow an 'agnostic approach', such as ASOs (as Graham did in D19). Finally, the Defendant submits, even if the skilled person would have considered an antibody approach, they would not inevitably have ended up with antibodies that fall within the scope of the claim. These arguments do, however, not convince the Central Division.
Lagace teaches the skilled person that PCSK9 functions extracellularly in vivo
' considerable amounts of PCSK9 circulate in plasma and provided a range of physiologically relevant PCSK9 concentrations .' (C3 2996, rh. col., second par.)
and on p. 3002, lh. col. last par. - 3002, rh. col. top:
' Considered together, the available data now suggest that PCSK9 can function both extra- and intracellularly, but we do not know which pathway predominates under normal and/or pathologic conditions. Currently, all studies suggesting that the protein functions intracellularly have been performed using PCSK9 overexpression via a strong CMV promoter. Overexpression may permit association of PCSK9 and the LDLR in an intracellular compartment that does not occur physiologically. In the current studies, we were able to demonstrate that physiologically relevant concentrations of PCSK9 could significantly reduce the number of cell-surface LDLRs ' (underline CD).
every experiment in a prior art document in isolation with a view to the questions it does not answer but will rather be inclined to accept published (and peer reviewed) research results and reasonable conclusions drawn from those results at face value.
'A potential artifact of the cell -culture studies, adenoviral studies in the liver and the parabiosis studies relates to the supraphysiological amounts of PCSK9 used to generate LDLR degradation. Overexpression might promote an interaction between PCSK9 and the LDLR in a cellular compartment that does not usually occur.' (quote in 137 DtR, 36 Case Summary, underline CD).
' To address this issue, the circulating levels of PCSK9 in human plasma were measured and found to range form ~50 to ~600 ng ml-1. The concentration of purified PCSK9 needed to promote LDLR degradation (~500 ng ml-1) falls within this range [23].' (reference 23 is Lagace, underline added CD) (C11, p. 73 lh. col., last sentence, rh. col. first sentence, underline CD).
(C3a, Supplemental Figure 1)
accepted (there is no question mark in Figure 2 at the extracellular pathway, depicted on the right):
8.48 The acceptance of the extracellular pathway is furthermore confirmed in Qian et al . (C6). This article was published by a research team from the pharmaceutical company Eli Lilly. In early 2007, they report:
'…we have demonstrated that 1) secreted recombinant PCSK9 is fully functional in reducing LDLR protein levels both in cultured cells and in vivo; 2) PCSK9 undergoes LDLR-mediated endocytosis; and 3) PCSK9 binding to LDLR is critical for PCSK9 function.' (C6, p. 1494, rh. col. second par.).
This conclusion is based on the authors´ own research, including in vivo mice experiments ( see Figure 3, concluding in the caption to Figure 3 that ' PCSK9 recombinant protein reduces hepatic LDLR and increases plasma LDL cholesterol in vivo. ') and including an in vitro experiment showing that disrupting PCSK9 binding to the cell surface LDLR extracellular domain was sufficient to markedly attenuate PCSK9 function (Fig. 6 and p. 1497, lh. col. first par.). Qian et al . also refer back to the Lagace paper (reference 20 in Qian et al .). Based on these findings, Qian et al . provide a 'working model' in Figure 7 showing the role of PCSK9 acting (exclusively) as a secreted (extracellular) protein that interacts with LDLR.
8.49 The publications relied on by the Defendant, even if the Central Division were to accept in favour of the Defendant that, although most of these do not form part of the state of the art, their contents are representative of what was (not) known at the priority date about PCSK9´s mechanism of action, would not have raised substantial doubts in the mind of the skilled person on the existence of the extracellular pathway. At most these publications raise questions concerning the relative contribution of the extracellular pathway and a possible intracellular pathway. Lopez 2008 (C14) , for example, states ' [a]nother open question is whether PCSK9 acts primary [sic] as an intracellular or a secreted factor. ' (p. 189, lh. col. unde r 'Conclusion'). Grefhorst 2008 (D23, p. 1303) states: ' [c]urrently, the relative contribution of the intracellular pathway versus the exogenous pathway of PCSK9-mediated LDLR degradation is not known. ' (underline Central Division). Thus, none of these references calls into question the existence of the extracellular pathway as such. This is also true for McNutt (D25, published in 2009) which, despite the citation from the Abstract highlighted by the Defendant in par. 108 DtCC, indeed also seems to presuppose the existence and relevance of an extracellular pathway, e.g. see the further quote by Defendant in par. 199 DtCC : ' address an unresolved issue in PCSK9 biology, whether PCSK9 functions primarily intracellularly to degrade LDLRs or as a secreted protein that acts on LDLRs at the cell surface. ' (underline CD.). Poirier (D26) likewise focussed on the ' relative contribution of the intra- versus extracellular pathway ' (see citation 202 DtCC, underline CD). In fact, Poirier confirms that
even if there was uncertainty in relation to the relative contribution of the intra- versus the extracellular pathway, this would not affect the viability of an approach directed towards the extracellular pathway for the treatment of hypercholesterolemia, see D26, Abstract, la st sentence: ' Therefore, targeting either pathway, or both, would be an effective method to reduce PCSK9 activity in the treatment of hypercholesterolemia and coronary heart disease. ' (underline CD).
is mentioned as one of the inventors, it is stated: ' The secreted form of PCSK9 appears to be the physiologically-active species ' (C37, par. [0006]).
'The low plasma LDL-C levels associated with loss-of-function mutations in PCSK9 indicate that inhibition of PCSK9 either through small molecules, antibodies or RNAi should be effective cholesterol-lowering drugs independently of statins.' (C11, p. 75, lh col. second par., last sentence).
'Genetic evidence suggests that PCSK9 is an attractive target for the treatment of cardiovascular disease. In theory, PCSK9 could be targeted by a cell-permeable protease inhibitor that prevents its self-processing and secretion and so delivers an effect similar to those of PCSK9 loss-of-function mutations. As plasma LDLR binding and receptor dependent endocytosis is probably the rate-determining step for PCSK9 function, antibodies or small molecules that bind plasma PCSK9 and disrupt its association to LDLR may also be effective inhibitors of PCSK9 function. Our structure reported here, and ultimately that of the PCSK9-LDLR complex, will be valuable for designing novel therapies.' (C8, p. 418, underline CD)
of other 'inhibitors' than inhibitory antibodies does not imply that the skilled person would not have pursued the obvious route of antibodies or would have lacked a reasonable expectation to do so. Equally, the fact that Graham (D19) investigated antisense inhibition of PCSK9 and concludes that this is an attractive and novel therapeutic approach for treating hypercholesterolemia in human (Graham, Abstract, last sentence) does not, realistically, mean that the skilled person would not, or with necessarily lower expectations, follow up on the suggestion in Lagace to follow an antibody approach.
8.59
Defendant argues that PCSK9 in plasma would have been considered as ' functionally inert ' by the skilled person because of its low binding affinity to LDLR at neutral pH in combination with its plasma concentration (RtCC 9.a). This would amount to a reason why the skilled person would have no reasonable expectation of success to take an antibody approach. However, the existence of such doubts is not supported by the prior art documents relied upon by Defendant. Cunningham (C11), despite the statement referred to by the Defendant in 212 RtCC, concludes that ' antibodies … that bind plasma PCSK9 and disrupt its association to LDLR may also be effective inhibitors ' (underline CD). Likewise, Lagace discloses to the skilled person, and Dr. as an inventor (see citation above, 8.50) included in a contemporaneous patent application, that extracellular PCSK9 was a promising target indeed whereby Lagace explicitly measured and discussed the plasma levels of PCSK9 in humans. Fischer 2007 (C7) does not say anything that would lead the skilled person to a different conclusion. To the contrary, they conclude: ' Together, the results of our biochemical and cellbased experiments suggest a model in which secreted PCSK9 binds to LDLR and directs the trafficking of LDLR to the lysosomes for degradation. ' (final
sentence, Abstract, underline CD).
8.60 It has therefore not been established that the skilled person would see the plasma concentrations of PCSK9 and/or the binding affinity to LDLR at neutral pH as a serious obstacle to developing an antibody treatment for hypercholesterolemia and the related conditions claimed.
8.61 In a similar vein, the Defendant has not made sufficiently plausible that the possible 'sequestration' o f therapeutic antibodies would have been a real concern for the skilled person who was considering to develop an antibody therapy directed against the PCSK9/LDLR interaction. Sequestration by a ' pool of inert PCSK9 in the circulation ' (227 DtCC) would acco rding to the Defendant cause the skilled person to doubt that the administration of antibodies would achieve sufficient concentrations at the liver cell surface to have any therapeutic effect. First of all, none of the prior art documents on file mention sequestration of antibodies as a problem, let alone in relation to proposed anti-PCSK9 antibodies. Even if it would be accepted that PCSK9 antibodies would after injection or infusion encounter PCSK9 in the circulation, given the expected relevance of plasma PCSK9 as a therapeutic target (see above), the Defendant has not made clear how such 'sequestering' of antibodies by PCSK9 would be anything different from (therapeutically useful) binding to PCSK9 to block its interaction with the LDLR.
8.62 According to the Defendant, the skilled person would furthermore lack a reasonable expectation of success because there would be doubts that antibodies would be able to reach the relevant sites of action at the liver surface due to the architecture of liver cells. The Claimants rebut stating that (to the contrary) the skilled person would have expected a protein expressed in the liver such as PCSK9 to be particularly accessible to antibodies and amenable to antibody therapy. The issue of liver architecture can remain open (whereby the Central Division does note that the claims of the Patent are not limited to a use in the treatment of atherosclerotic vascular disease as the Defendant and Dr. seem to wrongfully presume in their rejoinder to Claimants´ reply on this point, see 170 R, with reference to par. 7.1-7.2 E11) as the skilled person would have expected PCSK9 in plasma to be a relevant therapeutic target (as argued by the Claimants, also see above). Accessing the surface of liver cells would therefore not have been considered as a necessity for the skilled person whose aim was to find a treatment of the conditions as defined in the claims.
8.63 There were according to Defendant further doubts because of PCSK9´s presumed high turnover rate in vivo (232 DtCC). The existence of such doubts,
let alone that these doubts would have affected the skilled person´s reasonable expectation of success at the relevant date has not been adequately substantiated by the Defendant, especially given Claimants´ responses. Document D23 ( Grefhorst ) which is relied upon in this context ' ' does not form part of the prior art and therefore cannot -without further explanation which is lacking -contribute to the skilled person´s expectations on the relevant date. It has furthermore not been disputed by the Defendant that antibodies against protein targets having a high turnover rate in vivo , such as TNFα, were commonly known and had been successful in the clinic before the relevant date. Even if it would be accepted that the skilled person would realise that antibodies were not a ' panacea for neutralizing proteins with high turnover rates ' (181 DtCC) and even if the knowledge about anti -TNFα antibodies would have been regarded as irrelevant as argued by the Defendant, this in any event does not support the conclusion, that at the relevant date there would be no reasonable expectation of success for the skilled person absent any concrete information about the turnover rate of PCSK9 and the conclusions the skilled person would draw therefrom in the prior art.
8.64 Finally, the Defendant argued that there were doubts that antibodies binding to the catalytic domain could disrupt PCSK9/LDLR interaction. In this respect, the Central Division does not attach weight to the statement in a Schering patent application (C38, filed on 27 October 2008 with a priority date of 26 October 2007, published 30 April 2009) that finding a blocking antibody would be unlikely given the large sizes of the proteins PSCK9 and LDLR. In any event, C38 was published on 30 April 2009 and is not part of the prior art and therefore cannot 'teach away' as argued by the Defendant (236 DtCC). The Central Division also does not see how Zhang (C4) would teach away from the claimed subject matter. First of all, Zhang (from the same research group as Lagace and Horton) confirms to the skilled person that recombinant human PCSK9 binds the LDLR on the surface of cultured hepatocytes and promotes degradation of the receptor after internalization (see Abstract), in other words: the extracellular pathway. The research of Zhang adds to previous publications that the binding site of PCSK9 on LDLR was localised to the EGFa domain of LDLR (Abstract). If anything, the teaching of Zhang would confirm to the skilled person that blocking the LDLR-PCSK9 interaction, as suggested by Lagace, (with the additional knowledge that PCSK9 interacts with the EGFa domain within the extracellular domain of the LDLR) was indeed a promising avenue to pursue. The fact that Zhang used a non-blocking polyclonal antibody as a research tool (for immunoprecipitation) has no bearing on the reasonable expectation of success of the skilled person to generate
(therapeutically useful) blocking monoclonal antibodies. The Central Division also fails to see why Cunningham (C8) and Piper (C12) would teach away by suggesting that other domains from PCSK9 may be important for the PCSK9/LDLR interaction, already for the reason that the claimed antibodies are not limited to antibodies that bind solely to the catalytic domain and cover antibodies that (in addition to binding to the catalytic domain) bind to the pro and V-domain of PCSK9 as well.
The skilled person would arrive at antibodies falling under the claim
transgenic mice. It is also not in dispute between the parties that these methods were known and routine at the priority date (cf. the technical background section above and E6, par. 39-41).
PCSK9 antibodies disclosed in the Patent (e.g. 304 DtCC). Defendant refers to the antibody generation and screening protocols which are disclosed in the Patent and were ' critical for success ' (with reference to D93, the declaration of Mr. Pan, an employee of the Defendant, who was involved in the PCSK9 project as of July 2006). The steps referred to by the Defendant mainly relate to the immunisation protocol and the immobilisation method for PCSK9 used for screening. At the oral hearing, the Defendant for the first time took the position that the skilled person would not have found antibodies falling under the claim using routine methods.
skilled person would not arrive at an antibody falling under the scope of the Patent claims using routine methods of antibody generation and selection as the Claimants have credibly argued supported by references to the common general knowledge (see e.g. 3.2.8 CC, 2.11 Case Summary) and as also follows from the above discussion.
' Binds to the catalytic domain '
by Lagace, they would ' pass the screen' and would meet the functional requirements of the claim. There would have been no technical reason for the skilled person to (include or) exclude any (functional, inhibiting) antibodies based on their binding location. This is already evidenced by 'reference antibody' 31H4 which binds to the catalytic domain and to the pro-domain. Conversely, as acknowledged by the Defendant, not all antibodies that bind to the catalytic domain will block PCSK9/LDLR binding and/or will have a therapeutic effect (R, 51). There is furthermore no teaching in the prior art that leads the skilled person away from antibodies binding to the catalytic domain (see above par. 8.64).
Conclusion on inventive step
that PCSK9 was seen as a very promising target for the treatment of these diseases at the relevant date. The skilled person would have developed such antibodies using routine techniques.
Application to amend (auxiliary requests)
9.2 The Defence to Revocation in the Revocation action and the Defence to the Counterclaim for Revocation in the Infringement action both include the same conditional application to amend the Patent (Rule 30 RoP which applies mutatis mutandis in a revocation action based on Rule 50 RoP). Various amendments were proposed by way of multiple alternative sets of claims (auxiliary requests 1-17 divided in five different ' sets ' of auxiliary requests ).
9.3 The Claimants have not argued that the Defendant´s application to amend does not meet the requirements of Rule 30.1 RoP. The Central Division sees no reason to find otherwise. The application to amend is therefore admissible.
9.4 The Claimants have raised several objections in relation to the requirements of Articles 84 and 123(2) EPC. It is not necessary for the Central Division to decide on these objections since the proposed claim amendments cannot in any event remedy the lack of inventive step found for the Main Request.
9.5 The proposed amendments were summarised by the Defendant as follows (Table 1, DtR, same Table 3 DtCC):
9.6 As follows from the submissions of the Defendant, auxiliary requests AR1AR9 (sets 1, 2 and 3) were filed to address various added matter objections raised by the Claimants (478 DtR). Auxiliary requests AR10-AR13 (set 4) were filed to address the priority attack (481 DtR). Auxiliary requests AR14-AR17 were also filed to address the priority attack (484 DtR).
9.7 The Central Division found that the claims of the Patent as granted (Main Request) lack inventive step. However, as can be seen from the Defendant´s submissions, none of the Auxiliary Requests has been submitted to address a lack of inventive step. As regards inventive step, the Defendant has merely stated that the claims of the auxiliary requests are inventive for the same reasons as the Main Request without providing any further explanation. Despite the extensive debate between the parties on (claim interpretation and) inventive step, at no point did the Defendant submit -and it is not apparent to the Central Division -that and how any of the auxiliary requests could serve as a basis for revocation of the Patent in part considering a lack of inventive step of the Main Request. Therefore, also taking into account
Table 1: summary of Auxiliary Requests
Article 76 UPCA, according to which a decision on the merits may only be based on grounds, facts and evidence, which were submitted by the parties, the Central Division concludes that Auxiliary Requests 1-17 lack inventive step for the same reasons as the Main Request.
9.8
Having heard the parties on all relevant aspects of the case, the Central Division:
Presiding judge: Ulrike Voß
Legally qualified judge and judge-rapporteur: András Kupecz
Technically qualified judge: Casper Struve
For the Deputy-Registrar
Natalie Gnaß
András Ferenc Kupecz Digital unterschrieben von András Ferenc Kupecz Datum: 2024.07.12 10:52:41 +02'00'
Casper af Casper Struve
Struve
Digitalt signeret
Dato:
2024.07.12
11:29:13 +02'00'
Ulrike Voß Digital unterschrieben von Ulrike Voß Datum: 2024.07.12 12:34:37 +02'00'
Natalie Digital unterschrieben von Natalie Gnaß Datum: 2024.07.15 09:55:33 +02'00'
Gnaß
An appeal against the present Decision may be lodged at the Court of Appeal, by any party which has been unsuccessful, in whole or in part, in its submissions, within two months of the date of its notification (Art. 73(1) UPCA, R. 220.1(a), 224.1(a) RoP).
Art. 82 UPCA, Art. Art. 37(2) UPCS, R. 118.8, 158.2, 354, 355.4 RoP.
An authentic copy of the enforceable decision will be issued by the Deputy-Registrar upon request of the enforcing party, R. 69 RegR.