T 0684/23 - A desirable antibody claimed as such

Key points

• "The invention relates to an antibody specific for free symmetrical dimethylarginine (SDMA) in a biological sample (claim 1),"
• The Board, under inventive step: "If the claimed antibody could not have been obtained by standard methods, its preparation could have been an invention in itself. However, the claimed antibody needs to be inventive on its own: it cannot be rendered inventive by means of any arguable difficulty in obtaining it."
•  Compare T 595/95: "A product which can be envisaged as such with all the characteristics determining its identity including its properties in use, i.e. an otherwise obvious entity, may become non-obvious and claimable as such, if there is no known way or applicable (analogy) method in the art to make it and the claimed methods for its preparation are the first to achieve this and do so in an inventive manner" (add, after G 1/23: and the product was not commerically available)
• " The parties also referred to the expectation of success in the context of the claimed antibody. However, whether there was a reasonable expectation of obtaining the claimed antibody has no bearing on its inventiveness. It may at best have relevance in the context of its preparation."
•  "The problem underlying the claimed invention [was] providing an improved method for evaluating renal function, achieving lower costs, improved time effectiveness and increased reliability."
• "The respondent [proprietor] did not dispute that the link between SDMA and renal function was known from D8. "
• "Claim 1 merely specifies the pre-eminent properties of an antibody for an SDMA assay: total specificity and direct application on serum. An assay relying on an antibody with those properties would have been an obvious improvement to a skilled person. This is the case regardless of whether an antibody with those properties was within the reach of a skilled person at the filing date: what is relevant is whether the features in claim 1 are obvious."

EPO 

The link to the decision is provided after the jump.

T 2049/23 - Watermelons and discoveries

Key points

• The opponents include "Keine Patente auf Saatgut! e.V.". The patent concerns a conventionally-bred watermelon.
• The opponent argued that "the transitional period created by opinion G 3/19 should not be taken into account and that it did not matter whether the patent applications were filed before or after July 2017."
• The present Board: "in order to ensure legal certainty and to protect the legitimate interests of patent proprietors and applicants, the Enlarged Board of Appeal [in G 3/19] further decided that "the new interpretation of Article 53(b) EPC given in this opinion has no retroactive effect on European patents containing such claims which were granted before 1 July 2017, when Rule 28(2) EPC entered into force"
• It seems that the opponent did not invoke Article of the AC decision that inserted Rule 28(2): "This decision shall enter into force on 1 July 2017. Rules 27 and 28 EPC as amended by Articles 1 and 2 of this decision shall apply to European patent applications filed on or after this date, as well as to European patent applications and European patents pending at that time" (OJ EPO 2017, A56). This is a pity, because the EBA did not expressly set aside that part of the AC's decision.
• On inventive step:  the appellants  [opponents] submit that the claimed watermelon plants having a bush growth habit constitute a discovery rather than an invention. The board understands this as an objection under Article 100(a) and Article 52(2)(a) EPC to the effect that the claimed subject-matter is not a patentable invention but a discovery.'" 
•  "According to the case law of the Boards, a substance which occurs in nature can be considered an invention when it is shown to give rise to a technical effect. This principle is reflected in Rule 27(a) EPC, according to which biotechnological inventions are 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. 
• For example, if a microorganism is found in nature and shown to produce an antibiotic, the microorganism itself may also be patentable as one aspect of the invention. 
• Similarly, a gene which is discovered to exist in nature may be patentable if a technical effect is revealed, e.g. its use in making a certain polypeptide or in gene therapy
•  "The board considers that the plants (and plant tissues) of claims 1 to 16 do not constitute a discovery." 
• "While the "home-garden diploid watermelon [with] an interesting growth type" mentioned in paragraph [0119] of the patent [] could be argued to be a discovery, it is not part of the claimed subject-matter. Instead, the mutated allele present in said plant has been transferred to other plants (i.e. those producing seedless fruit) and these have been shown to produce a technical effect: as set out in paragraph [0001] of the patent "this plant can be grown at a higher density in the field compared to traditional non-bush triploid watermelon hybrids, leading to a higher fruit yield per hectare compared to triploid hybrids with normal growth habit (having an average longest vine length of above 200 or above 300 cm)"."
• The appeal is dismissed. 

EPO 

The link to the decision can be found after the jump.

T 0326/22 - Functional antibody claims

Key points

• The reports of the death of functional antibody claims are greatly exaggerated (see epi Information 2024/4), as this case shows.
Claim 1 reads: ""1. An isolated monoclonal antibody or immunologically active fragment thereof that binds to human CD47, wherein the antibody or immunologically active fragment thereof binds to a discontinuous epitope on CD47, wherein the discontinuous epitope comprises amino acids residues Y37, K39, K41, K43, G44, R45, D46, D51, H90, N93, E97, T99, E104, and E106 of CD47 when numbered in accordance with SEQ ID NO: 147,
and wherein the antibody or immunologically active fragment thereof prevents CD47 from interacting with signal-regulatory-protein a (SIRPalpha)
and does not cause a significant level of agglutination of cells after administration.""
• Hence, the definition of the claim is purely functional. The SEQ ID refers to the structure of the epitope (target), not the structure of the antibody itself.
• For sufficiency:  In these circumstances the issue to be assessed is whether the skilled person based on the patent application's teaching taking common general knowledge into account can reliably and without inventive skill find those antibodies in the pool of generated CD47 antibodies that show the functional properties indicated in claim 1."" 
• "as long as the generation of these further CD47 antibodies requires nothing but routine work that may be tedious and time consuming, the method of generating these antibodies cannot be regarded per se as being based on undue burden (T 431/96, Reasons 6)."
•  "the patent application provides the skilled person with the sequence information of the six CDRs of the 2A1 antibody and of various derivatives thereof including their full variable light and heavy chain sequences (Table 1 on pages 32 and 33, paragraphs [00111] and [00112]). Antibodies with these sequences fulfil the functional properties indicated in claim 1. It is also uncontested that varying these sequences and obtaining further antibodies are routine and hence impose no undue burden on the person skilled in the art. Thus, in agreement with the appealed decision (point 14.1 of the Reasons), the board considers that the skilled person in following this route routinely arrives at further antibodies with the functional properties of claim 1."
• "Example 11 of the patent application mentions that X-ray crystallography ("XRC") was used for determining the epitope structure on CD47 bound by the chimeric antibody 2A1-xi and discloses the epitope's structural information (see also Figure 11C). "
• It is unclear to me if the patent provides for an assay for the feature of the binding to the specified epitope and if the skilled person can easily screen for antibodies having that property, other than obtained by varying the example antibody 2A1.
• After a detailed technical analysis: "In view of the considerations above, it is credible that the skilled person by applying the teaching of the patent application and taking common general knowledge into account would arrive without undue burden at further antibodies falling within the scope of claim 1. "
• On inventive step: "Compared to the full-length B6H12 and 5F9 antibodies of document D1, the objective technical problem to be solved resides thus in the provision of an improved CD47 antibody."
• "Document D1 provides no pointers for the skilled person to select the epitope on CD47 as defined in claim 1 for solving the technical problem formulated above. Thus the claimed antibodies are based on an inventive step over the disclosure of the full-length monospecific and bispecific B6H12 and 5F9 antibodies of document D1."
• The claim request is held to comply with the EPC.

EPO 

The link to the decision can be found after the jump.

T 1553/22 - Human-pig chimeras

Key points

• "Claims 3 [] of auxiliary request 2 read as follows: "3. A chimeric non-human blastocyst expressing human ETV2 and lacking expression of said non-human animal ETV2, wherein the blastocyst is porcine."
• "The application concerns the generation of pig-human chimeric animals with the aim of using them as a source of human vasculature and blood. The chimeric pigs are obtained by methods involving "blastocyst complementation". This involves creating a non-human (host) blastocyst lacking one or more genes involved in the development of the cells of interest. This creates a so-called "niche" which is complemented by introducing into the blastocyst human pluripotent (donor) cells having those lacking genes. Specifically, in the application, the host blastocyst lacks the Etv2 gene, whose function is to promote hematoendothelial development"
• " claims 3 and 4 do not include language that would exclude chimeras having human cell participation in the brain or germ cells."
• The applicant is a university.
• "In the appealed decision, the examining division refused the application for ethical reasons pursuant to Article 53(a) in conjunction with Rule 26(1) EPC and Recital 38 of the Directive 98/44/EC of 6 July 1998 on the legal protection of biotechnological inventions (point 4.16 of the Reasons). "
• The Board: " The ethical dimension of patent law has found its expression in Article 53(a) EPC, together with the implementing regulations in Rules 26 to 29 EPC. These Rules were introduced in the EPC to align the EPC with the Directive 98/44/EC of 6 July 1998 on the legal protection of biotechnological inventions (the "EU Biotech Directive"). In order to achieve harmonised protection in the field of biotechnological inventions in Europe, the EU Biotech Directive provides a supplementary means of interpretation for the EPC (Rule 26(1) EPC). Thus, when the compliance of a biotechnological invention with ethical principles has to be assessed, the legal framework is a composite one, in the sense that the EPC provisions should be understood in the light of the EU Biotech Directive, also including considerations which are outside the strict patentability requirements."
• "Human-animal chimeras are not mentioned in Rule 28(1)(a) to (d) EPC, nor in the provision from which this Rule is derived, namely Article 6(2) of the EU Biotech Directive. However, specific forms of human-animal chimeras are mentioned in Recital 38, which relates to the illustrative list of exclusions for reasons of ordre public and morality provided in Article 6(2) of the EU Biotech Directive. Recital 38 includes the following wording:

"...whereas processes, the use of which offend against human dignity, such as processes to produce chimeras from germ cells or totipotent cells of humans and animals, are obviously also excluded from patentability;".

• "Recital 38 does not exclude chimeras as such, but specifically identifies processes to produce chimeras from germ cells or totipotent cells of humans. Since the present invention involves the use of pluripotent cells, which are distinct from totipotent cells and germ cells, it can be said that Recital 38 does not apply directly.
• This sets up the legal puzzle: if the EU legislator intentionally did not wish to exlcude human-animal chimeras in general (and, at the time of drafting, did not think of pluripotent cells, perhaps), what is excluded? Only the recited type of chemiras? Or some intermediate class?
• "The board takes the view that the exclusion of Article 53(a) in conjunction with Rule 28(1) EPC may extend to other chimeras, where the rationale underlying the examples identified in Recital 38 is also applicable to the chimeras concerned. Thus, by means of Rule 26(1) EPC a further special case is added to the non-exhaustive list of Rule 28(1) EPC."
• Rule 26(1): "For European patent applications and patents concerning biotechnological inventions, the relevant provisions of the Convention shall be applied and interpreted in accordance with the provisions of this Chapter. Directive 98/44/EC of 6 July 1998 on the legal protection of biotechnological inventions shall be used as a supplementary means of interpretation."
• "the board finds that the reason why the chimeras identified in Recital 38 are regarded as offensive against human dignity is due to concerns that, in chimeras including human germ cells or totipotent cells, these human cells may integrate into the brain and/or develop into germ cells and result in a chimera with human or human-like capabilities. 
•  This reason is straightforward for chimeras including totipotent cells, which in view of their developmental capability to form an entire organism may form a brain with human-like cognitive abilities or human germ cells. 
• The Board finds it 'straightforward', but that may be a case of hindsight in solving a legal problem.
• "However the same reason applies to pluripotent cells, which despite lacking the ability to differentiate into totipotent cells or cells of the placenta, nevertheless have the ability to differentiate into neural cells or germ cells. Thus, if an invention relates to a situation where human cells might integrate into the chimera's brain, potentially giving the chimera human-like cognitive or behavioural capabilities, or into its germ line, potentially giving it the ability to pass on humanised traits, the board considers that the underlying rationale of Recital 38 of the Directive would be relevant and shall be taken into account in examining compliance with Article 53(a) in conjunction with Rule 28(1) EPC."
• "the board does not consider it necessary to refer to the preparatory work to the EU Biotech Directive. Whereas the recourse to the preparatory work is possible as supplementary means of interpretation under Article 32 Vienna Convention, the board finds that in the present circumstances there is no ambiguous or obscure meaning in the wording of the exclusions in Recital 38 which needs to be clarified, nor does the interpretation on account of its object and purpose lead to a result which is manifestly absurd or unreasonable."
• Article 32 Vienna Convention indeed limits the use of the preparatory documents to these two cases, though the EPC travaux are cited more freely by the Boards.
• "With regard to the present case it must therefore be established whether the invention defined in claims 3 to 5 includes embodiments that fall under the scope of Recital 38 [by analogy?], thus contravening the requirements of Article 53(a) EPC in conjunction with Rule 28(1) EPC. Specifically, it must be determined whether the claims define chimeras and methods of producing chimeras including embodiments where human cells participate in the brain or germ cells of the chimera."
• "Document D15 is a scientific article on research into ways of regulating the differentiation of the donor cells into the endodermal organs, in order to address concerns that human cells might be present in the germ line or participate in the brain of chimeras resulting from blastocyst complementation. These ethical concerns are set out prominently in the abstract of the document:"Blastocyst complementation, which exploits the capacity of PSCs to participate in forming chimeras, does not, however, exclude contribution of PSCs to the development of tissues - including neural cells or germ cells - other than those targeted ..."."
• "Even years after the date of filing of the application, these concerns remained undiminished, as evidenced by documents D9 and D10, which were made available to the public in 2019 and 2021 respectively."
• " On the basis of the documents on file and on the balance of probabilities, the board can only conclude that there is no technical reason to dismiss the ethical concerns, raised in the relevant literature, that human cells may be present in the brain or germ cells of a chimera according to the present invention. These concerns are relevant for chimeras resulting from the method defined in claim 5, as well as for the chimeras as defined in claims 3 and 4. This conclusion also takes into account that the method defined in claim 5 has no limitations as regards either the number of human cells injected in step (c) and that claims 3 and 4 do not include any limitations as to the number of human cells or exclude their presence in the brain or germ line."
• The relevant date is the filing date, I understand: "14. The assessment of objections under Article 53(a) EPC, as well as under Rule 28(1) EPC, should be based on the understanding in the technical field at the relevant date of the patent application, although evidence arising after that date may be taken into account, provided it reflects the state of the art at the effective date (see decision T 315/03, Reasons 8.2, 9.5, 9.7 and 10.9)."
• Cf. G 2/08: "Rule 28(c) EPC (formerly Rule 23d(c) EPC) forbids the patenting of claims directed to products which - as described in the application -  at the filing date could be prepared exclusively by a method which necessarily involved the destruction of the human embryos from which the said products are derived, even if the said method is not part of the claims." (not cited in the present decision; and Article 83 EPC might be relevant here).
• "the appellant stressed also the dramatic importance of the present invention in the field of xenotransplantation, potentially the very first step to repair and replacement technology which was previously regarded as pure science fiction. This fact should be balanced against the unsupported ethical concerns raised by the examining division."
• "The board recognises the importance of the present invention. However, for the reasons stated above, balancing tests are irrelevant in the context of the categories of inventions which are excluded from patentability ipso facto. Considerations involving balancing the potential benefits of the invention for humanity/the medical benefit against prejudice to human dignity/animal suffering, are limited to the so-called "real" Article 53(a) EPC objections or to inventions related to the genetic modification of animals within the meaning of Rule 28(1)(d) EPC. Instead, where the legislator wanted to exclude inventions offending life and human dignity as such, there can be no room for manoeuvre (see also G 2/06, Reasons 31)."
  
  
• "since the claims were not drafted to exclude embodiments where human cells are present in the brain and/or germ cells of the chimera (for instance by the inclusion of features based on technologies capable of preventing the presence of human cells in the brain and/or germ cells of the chimera) the board did not have to decide on the patentability of such subject-matter."

• As a comment, if these "technologies capable of preventing the presence of human cells in the brain and/or germ cells of the chimera" are now available and common general knowledge, the Art. 53(a) EPC objection can be addressed with an undisclosed disclaimer (G2/03), most likely, and Article 83 EPC is complied with by the availability of these preventive technologies (and appropriate reference to them in the application as filed).
• 
  
• 
  
• Suppose the preventive technologies also work for the chimeras from germ cells or totipotent cells of humans and animals" are these then patentable (under a dynamic interpretation, perhaps)?

EPO 

The link to the decision can be found after the jump.

https://www.epo.org/en/boards-of-appeal/decisions/t221553eu1

T 3122/19 - Functional compositions for second medical uses

Key points

• Claim 1 reads: "1. A compound having FGFR inhibitory activity or a pharmaceutically acceptable salt thereof for use in a method of treating or preventing cancer
  - in a patient who has been identified to express a fusion polypeptide comprising an FGFR3 polypeptide and a BAIAP2L1 polypeptide or to carry a polynucleotide encoding the fusion polypeptide, [wherein the polypeptide expressed in the patient has a certain sequence]
  - wherein the compound or a pharmaceutically acceptable salt thereof is capable of inhibiting a growth of a cancer cell expressing the fusion polypeptide or having a nucleotide encoding the fusion polypeptide."
• The compound is hence only defined in functional terms. 
• The Board: "Claim 1 (see section I.) is a purpose-restricted product claim directed to a compound having "FGFR inhibitory activity" for use in a method of treating or preventing cancer in a patient who has been identified as expressing a particular biomarker or as carrying a polynucleotide encoding it. This biomarker is a fusion polypeptide comprising an FGFR3 polypeptide and a BAIAP2L1 polypeptide, each polypeptide being defined by particular sequences. The claim further specifies that the claimed compound is capable of inhibiting the growth of a cancer cell expressing this fusion polypeptide or having a nucleotide encoding it."
• The Board, under sufficiency: "[the question is]  (1) whether the skilled person would have been able, based on the disclosure in the application as filed and/or on their common general knowledge, to obtain compounds as defined in claim 1 without undue burden. These compounds are defined by two functional features, namely that (i) they have FGFR inhibitory activity and that (ii) they are capable of inhibiting the growth of a cancer cell expressing the fusion polypeptide comprising an FGFR3 polypeptide and a BAIAP2L1 polypeptide."
• "in addressing issue (1), [the opponent] referred to the approach developed in particular in decision T 1063/06 (OJ EPO 2009, 516) in the context of so-called "reach-through" claims. The appellant [opponent] argued that the patent did not enable the skilled person to identify all compounds falling within the broad dual-function definition of the claim without undue burden and, accordingly, such alternatives were not available to the skilled person.

• " The board is of the opinion that the situation underlying decision T 1063/06 is not the same as that in the case at hand. The invention at stake in T 1063/06 was based on the discovery that a known illness (in this case cardiovascular disease) could be treated by compounds having the capability of stimulating the soluble guanylate cyclase enzyme independently of the heme group in the enzyme, i.e. the compounds stimulated both the heme-containing soluble guanylate cyclase enzyme and the heme-free soluble guanylate cyclase enzyme. No compounds having this capability were known in the art and such compounds could only be identified by means of a newly disclosed screening method as a new research tool. The claim under consideration in that decision was thus for the use of (hitherto unidentified and thus unknown) compounds, which were defined solely in terms of the specific new capability (function), for the manufacture of a medicament to treat a known illness.

• " By contrast, the invention underlying the case at hand relates to the identification of a subgroup of cancer patients which is susceptible to treatment with FGFR inhibitors. The inventors found that a known human cancer cell line (SW780), which was known to be susceptible to the antiproliferative effect of known FGFR inhibitors, expresses a fusion polypeptide of the FGFR3 polypeptide and the BAIAP2L1 polypeptide which was also identified in various other types of human-derived cancer cells. The claim under consideration is for FGFR inhibitors which have the capability of inhibiting the growth of cancer cells expressing a FGFR3-BAIAP2L1 fusion polypeptide for use in a method of treating cancer in patients who express a FGFR3-BAIAP2L1 fusion polypeptide. This is not the same situation as in T 1063/06, in which any kind of compound (without guidance in terms of chemical structure or other selection rules) would have to be screened for the desired enzyme-stimulating activity."

• "Numerous FGFR inhibitors were known from and made available in the art, and are also identified by their chemical names or structures in the application as filed. These constitute a large pool of candidates. Together with the general structural and functional requirements mentioned in the application as filed, this information would, moreover, have provided some orientation to the person skilled in the art for identifying further FGFR inhibitors, if required"

• "Testing for the second level activity against cancer cells (as described in the application as filed) would not have had to be carried out by trial and error on randomly selected compounds, but only on a limited selection of compounds, i.e. compounds chosen from the class of FGFR inhibitors. No evidence was provided to show that a large proportion of FGFR inhibitors would fail this test (in which case identifying active compounds would be an undue burden on the skilled person). "

• Regarding another decision:" In the case underlying T 1959/15, the invention resided in providing a further class of compounds for treating the disease; in the present case, the invention resides in the identification of the specific genetic make-up of a subgroup of patients who are particularly susceptible to treatment with a known class of compounds. For this reason alone, the findings in decision T 1959/15 do not directly apply to the facts and circumstances of the case at hand."

• In a way, we are patenting a diagnostic method, it seems.

• "unlike the conclusion in T 1959/15 for the claim at stake therein, for the reasons already set out in point 57. above this board takes the view that under the circumstances of the case at hand, the mere fact that claim 1 also covers compounds beyond those shown to be suitable for the therapeutic use does not automatically equate to an undue burden of screening arbitrary compounds. Moreover, this does not result in the claim being able to be classified as a "reach-through" claim."

• There are more interesting issues in the case, e.g. making the claim novel and inventive by adding "wherein said patient is a human patient"

EPO 

The link to the decision and an extract of it can be found after the jump.

T 0419/16 - Inventive step of first medical use

Key points

• The decision deals with inventive step of a first medical use claim in the format of Article 54(4) EPC.
• "The purpose given in the claim is "for use as a medicament". The board also notes that according to the patent, the claimed antagonist is useful specifically in the treatment of "a disorder or condition selected from the group consisting of asthma; allergy; multiple sclerosis; or arthritis" (see paragraph [0011] and claim 4 of the patent as granted). "
• Claim 1 is, moreover, a functional antibody claim: "1. An antagonist of IL-33 for use as a medicament, wherein the antagonist comprises a binding composition from an antibody that specifically binds to IL-33."
•  The opposition division came to a positive decision on inventive step, assessed solely when starting from the disclosure in document D6 representing the closest prior art. The appellants [opponents] however consider the disclosure in several (different) documents (documents D3, D4 or D6/D10) as starting points for assessing inventive step."" 
• "Although assessing inventive step only from one closest prior art disclosure may constitute an efficient approach to address the situation where multiple similar disclosures were presented as starting points for the assessment of inventive step, it is, however, not an appropriate approach if the alternative starting points represent alternative and different routes to the invention, as they do in the case at hand. In such a situation, each starting point needs consideration because under Article 56 EPC, in order for an inventive step to be acknowledged, the claimed invention must not be obvious to a skilled person having regard to the state of the art, i.e. any prior art disclosure with the exclusion of documents under Article 54(3) EPC (see T 694/15, Reasons 13 to 15, T 816/16, Reasons 3.7.1 and T 261/19, Reasons 2.5)."
• For inventive step over D6: "the difference between this [antibody of D6] and the claimed antibody is the target (ST2/IL-33 receptor) and its medical use(s) both in general and the specific uses identified in the description of the patent (treating asthma, allergy, multiple sclerosis and arthritis)."
• "The objective technical problem that arises out of the above differences and their technical effects can be formulated as the provision of a medicament, e.g. for treating asthma, allergy, multiple sclerosis and arthritis."
• The decision is interesting because for inventive step of product claims, we normally consider only at the use mentioned in the description. 

EPO 

The link to the decision and an extract of it can be found after the jump.

T 0835/21 - A valid functional antibody claim

Key points

• This case seems to illustrate that there is no Amgen v. Sanofi rule at the EPO. 
• Claim 1 is directed to an antibody defined purely in functional terms, i.e. in terms of what it binds to, without any restriction on the sequence/composition of the antibody itself.
• " A monoclonal antibody or an antigen-binding fragment thereof that specifically binds to human low-density-lipoprotein receptor-related protein 6 polypeptide (LRP6) having the amino acid sequence of SEQ ID NO:1, is capable of antagonizing the Wnt signaling pathway, and inhibits Wnt3- and Wnt3a-specific signaling activity, wherein the antigen binding portion binds to an epitope of human LRP6 within amino acids 631-932 of SEQ ID NO:1 as shown in Table 1." 
• On Art.83: " The preparation of a monoclonal antibody that binds to an epitope within a defined amino acid sequence, i.e. a known target, for example by immunisation of an animal with a protein or peptide consisting of or contained within the defined amino acid sequence, or by phage display using such a peptide, is a routine task for the skilled person and does not require any inventive activity. " 
• " The scant number of exemplary Fabs disclosed in the application, the lack of disclosure of the sequences of these exemplary Fabs, the lack of a direct link between Tables II and III of the application and the missing figures are hence not in themselves sufficient to call into question the general teaching in the application that the Wnt ligands fall into two groups which are preferentially antagonised by LRP6 antibodies binding to different propeller regions of LRP6, a teaching which is incidentally supported by post-published documents D2 and D5. Therefore, this argument does not persuade the board either." 
• On inventive step: " Document D8 discloses a monoclonal antibody that binds to the propeller 2 domain of LRP6 and inhibits Wnt3a-induced signalling activity (see point 52. above). The claimed antibody differs from this in that it binds to an epitope within amino acids 631 to 932 of SEQ ID NO:1, i.e. to an epitope within the propeller 3 domain of LRP6. Moreover, document D8 is silent on whether or not the inhibition of Wnt3a-induced signalling that it discloses is Wnt3- and Wnt3a-specific, as required for the claimed antibody. " 
• " The objective technical problem can therefore be formulated as the provision of an antagonistic LRP6 antibody that preferentially inhibits Wnt3 and Wnt3a signalling activity over signalling activity induced by other Wnt ligands "
• "  Nothing in the prior art pointed the skilled person towards an antibody that bound to an epitope within the propeller 3 domain of LRP6 as a solution to this technical problem. Indeed, it was not known in the art that different Wnt ligands bound to different propeller domains of LRP6, and that therefore antibodies that preferentially inhibited the signalling activity induced by particular Wnt ligands could be prepared by targeting different LRP6 propeller domains. The link between binding to the propeller 3 domain of LRP6 and preferential inhibition of Wnt3 and Wnt3a signalling activity was therefore not suggested in the prior art and hence was not obvious to the skilled person." 
• " it was not obvious to the skilled person, solely from the fact that Dkk1 binds to the LRP6 propeller 3 domain, that an LRP6 antibody that bound to the propeller 3 domain would inhibit Wnt3- and Wnt3a-specific signalling activity. This line of argument is therefore not persuasive. No other arguments that took the preferential inhibition of the Wnt3- and Wnt3a-induced signalling activity by the claimed antibodies into account were submitted by the appellant. Hence, the claimed subject-matter involves an inventive step over the antibody disclosed in document D8."
  

The link to the decision is provided after the jump.

T 0435/20 - Anti-IL-23 antibodies binding at conformational epitope

Key points

•  Claim 1 as granted: "1. An antibody ... that binds to  human IL-23p19 [i.e. subunit p19 of human interleukin-23] at an epitope comprising residues 82-95 and residues 133-140 of SEQ ID NO: 29."
• Hence, no sequence or structure of the antibody is specified, only of the epitope, i.e. the substrate.
• The patent is roveked for insufficiency of the Amgen/Sanofi type (https://patentlyo.com/patent/2022/11/rethinking-enablement-grants.html) 
• The Board: "The claim is not for a single antibody but for a pool of antibodies each of which binds human interleukin-23 at an epitope as defined in the claim."
• "While the epitope bound by the claimed antibodies must include both stretches of amino acids, the claim does not unambiguously delimit the spatial extent of the epitope. Interpretation is therefore required to determine its extent. The board does this according to the normal rules of claim construction, in which the terms used in the claim are given their broadest technically sensible meaning in the context in which they appear and having regard to the common general knowledge and the teaching in the patent"
• "in an embodiment, although the claim is not limited to this embodiment, the claim encompasses antibodies that are functionally defined by their ability to bind to human IL-23p19 and contact several of the amino acid residues within both amino acid stretches recited in the claim, i.e. antibodies with the same specificity as the exemplified antibody 7G10 [i.e. the antibody shown in the examples of the patent, probably with the sequence specified in the sequence listing /description], but which are not structurally related to it."
• "Antibody 7G10 is therefore one way of performing the claimed invention. However, claim 1 is not limited to antibody 7G10 and structural related variants but encompasses antibodies which are solely defined by the functional feature that they have the same specificity as the exemplified antibody 7G10"
• That the skilled person can manufacture 7G10 based on the patent is not disputed.
• Turning to sufficiency, "In a first line of argument the appellant [patentee] submitted that, at the priority date of the patent, the generation and screening of antibodies that bind to the p19 subunit of hIL-23 did not amount to an undue burden of experimentation for a skilled person and that according to the case law of the Boards of Appeal, it was a matter of routine to raise and screen antibodies to a known antigen "
• "The board acknowledges that raising and screening antibodies involves only routine experimentation. However, this is the case only if the skilled person knows from the disclosure in the patent or from common general knowledge (i) which antigens are suitable for raising antibodies having the desired properties and (ii) which screening process should be used to select these antibodies without undue burden"
• " the generation and screening of antibodies that bind (anywhere) to the p19 subunit of hIL-23 would not involve an undue burden for the skilled person.  However, the patent in suit discloses neither a suitable antigen nor a screening process that would ensure the reliable generation and selection of antibodies having the required properties by applying routine methodology and a reasonable amount of experimentation. It is common ground that peptides consisting of the primary sequence of the claimed conformational epitope are unsuitable for raising the claimed antibodies or screening for them."
• "It is moreover undisputed that the patent does not disclose how antibody 7G10 was prepared, i.e. which antigen/immunogen was used for its generation or the screening process that was used to select for it. The board must therefore conclude that the patent contains no guidance regarding a suitable antigen or screening process for the generation and selection of antibodies that are structurally unrelated to antibody 7G10. "
• The Board then discusses the issue of sufficiency in more detail, discussing screening with ELISA, and the choice of the immunogen.
• "that the evidence on file does not support the appellant's assertion that suitable methods for screening a pool of anti-hIL-23 antibodies for p19-specificity were part of the skilled person's common general knowledge at the priority date. Since the patent provides no guidance in this respect either, the skilled person wanting to perform the claimed invention would have to develop a screening process for identifying antibodies that bind an epitope on the p19 subunit of hIL-23 and without risking to miss antibodies that bind the claimed conformational epitope, an undertaking that cannot be regarded as routine."
• "the functional definition of the claimed antibody amounts to an invitation to perform a research program without any guarantee of success. Such a situation is considered to amount to an undue burden for the skilled person "

• 
  

EPO 

The link to the decision is provided after the jump, as well as (an extract of) the text of the decision.

https://www.epo.org/law-practice/case-law-appeals/recent/t200435eu1.html

Main request (patent as granted) - claim 1

The claimed invention - claim construction

16. Claim 1 is directed to antibodies (or antigen binding fragment thereof) that bind to subunit p19 of human interleukin-23 (hIL-23p19) at an epitope comprising amino acid residues 82 to 95 and amino acid residues 133 to 140 of the amino acid sequence of mature hIL-23p19 (SEQ ID NO: 29). The claim is not for a single antibody but for a pool of antibodies each of which binds human interleukin-23 at an epitope as defined in the claim.

17. The two amino acid stretches recited in the claim are not contiguous along the primary sequence of the hIL-23p19 protein chain, thus the epitope defined in the claim is a so-called discontinuous or conformational epitope.

18. While the epitope bound by the claimed antibodies must include both stretches of amino acids, the claim does not unambiguously delimit the spatial extent of the epitope. Interpretation is therefore required to determine its extent. The board does this according to the normal rules of claim construction, in which the terms used in the claim are given their broadest technically sensible meaning in the context in which they appear and having regard to the common general knowledge and the teaching in the patent (see also CLBA, II.A.6.1).

19. The broadest technically sensible construction of the epitope defined in the claim is one where the epitope includes amino acid residues outside the two recited stretches of amino acids, recited in claim 1. Firstly, this is in keeping with the claim wording "comprising". Secondly, it is supported by dependent claim 2, according to which the bound epitope comprises 16 residues located within the recited stretches and 1 additional residue, H106, that is located outside these stretches. Indeed, the claimed antibodies need not bind exactly the amino acid residues recited in the claim as long as their epitope comprises these amino acid residues.

20. The appellant's submission that binding at least one amino acid residue in each stretch would be the broadest technically sensible interpretation is not found persuasive for the following reasons. First, the appellant's interpretation is not supported by the teaching of the patent in the general part of the description (see paragraph [0019] of the patent) and second, it is also no supported by antibody 7G10, relied on in this context by the appellant. Indeed, antibody 7G10 was determined by X-ray crystallography (X-RC) to be within 4.0 Å of the antibody (i.e. to "bind") at 9 of the 14 amino acid residues in stretch 82 to 95 of SEQ ID NO: 29 and 7 of the 8 amino acid residues in stretch 133 to 140 of SEQ ID NO: 29 (see paragraph [0180] of the patent).

21. Contrary to the decision under appeal, a technically meaningful interpretation of claim 1 does not require that it be implied that X-RC must be used to determine binding of the antibody at the target epitope. First, the use of X-RC is not a necessary consequence of the express language of the claim and thus not an implicit feature. Second, construction of the claim in light of the teaching of the patent does not imply the use of X-RC either. While the patent discloses that binding may be determined by X-RC (see paragraph [0019] of the patent), it discloses further methods for determining binding of the antibody at the epitope, (see e.g. paragraphs [0110], [0111] and [0113]).

22. Accordingly, in an embodiment, although the claim is not limited to this embodiment, the claim encompasses antibodies that are functionally defined by their ability to bind to human IL-23p19 and contact several of the amino acid residues within both amino acid stretches recited in the claim, i.e. antibodies with the same specificity as the exemplified antibody 7G10, but which are not structurally related to it. Binding to the conformational epitope may be determined by X-RC, but this is not mandatory.

Disclosure of the invention (Article 100(b) EPC)

23. According to the established case law of the Boards of Appeal, a patent complies with the requirement of sufficiency of disclosure if the skilled person, on the basis of the information provided in the patent and taking into account the common general knowledge, is able to perform the invention as claimed in the whole range claimed without undue burden, i.e. with reasonable effort (see CLBA, II.C.1).

24. The patent discloses, inter alia, a mouse anti-human IL-23p19 antibody termed 7G10 (see Tables 2 and 3), and a humanised version of this antibody, hum7G10 (see Example 2 and Tables 2 and 3). As mentioned in

point 20. above, antibody 7G10 was determined by X-RC to bind 9 of the 14 amino acid residues in stretch 82 to 95 of SEQ ID NO: 29 and 7 of the 8 amino acid residues in stretch 133 to 140 of SEQ ID NO: 29 (see Example 6).

25. Antibody 7G10 is therefore one way of performing the claimed invention. However, claim 1 is not limited to antibody 7G10 and structural related variants but encompasses antibodies which are solely defined by the functional feature that they have the same specificity as the exemplified antibody 7G10 (see also point 22. above).

26. For meeting the requirement of sufficiency of disclosure it is required that the patent, when considered in combination with the common general knowledge at the priority date, provides technical guidance which is sufficiently clear and complete to allow the skilled person to reliably obtain the above mentioned, functionally defined antibodies without an undue burden.

27. In a first line of argument the appellant submitted that, at the priority date of the patent, the generation and screening of antibodies that bind to the p19 subunit of hIL-23 did not amount to an undue burden of experimentation for a skilled person and that according to the case law of the Boards of Appeal, it was a matter of routine to raise and screen antibodies to a known antigen (see decision T 431/96).

28. The board acknowledges that raising and screening antibodies involves only routine experimentation. However, this is the case only if the skilled person knows from the disclosure in the patent or from common general knowledge (i) which antigens are suitable for raising antibodies having the desired properties and (ii) which screening process should be used to select these antibodies without undue burden (see also decision T 431/96, Reasons, points 6, 7, 10, 11, 12).

29. Indeed, the generation and screening of antibodies that bind (anywhere) to the p19 subunit of hIL-23 would not involve an undue burden for the skilled person.

30. However, the patent in suit discloses neither a suitable antigen nor a screening process that would ensure the reliable generation and selection of antibodies having the required properties (see

point 22. above) by applying routine methodology and a reasonable amount of experimentation. It is common ground that peptides consisting of the primary sequence of the claimed conformational epitope are unsuitable for raising the claimed antibodies or screening for them.

31. It is moreover undisputed that the patent does not disclose how antibody 7G10 was prepared, i.e. which antigen/immunogen was used for its generation or the screening process that was used to select for it. The board must therefore conclude that the patent contains no guidance regarding a suitable antigen or screening process for the generation and selection of antibodies that are structurally unrelated to antibody 7G10. For these reasons, the conclusion reached in decision T 431/96 that generation of antibodies to known antigens is routine, does not apply.

32. In a further line of argument the appellant maintained that the process of generating antibodies to hIL-23p19 involved immunisation with hIL-23 heterodimer to raise a pool of antibodies, and then identifying those antibodies that bind specifically to the p19 subunit. Selected anti-hIL-23p19 antibodies could then be analysed by X-RC to determine their epitopes. Since suitable methods for raising and screening antibodies were part of the skilled person's common general knowledge at the priority date, the requirement of sufficiency of disclosure was met.

33. The board is not persuaded by this this line of argument for the following reasons.

Choice of immunogen

34. The patent does not teach that the complete hIL-23 heterodimer should be used for the generation of antibodies that bind to hIL-23p19 at the claimed conformational epitope (see paragraphs [0079] and [0080] of the patent).

35. The appellant asserted that the common general knowledge would have led the skilled person to understand that not any fragment or the p19 monomer but the complete hIL-23 heterodimer (composed of a p19 and a p40 subunit) was the most suitable immunogen to raise antibodies that bind to hIL-23p19 at the claimed conformational epitope. No evidence supporting the pertinent common general knowledge was provided by the appellant.

36. Since p19 is one of the two subunits of hIL-23, the board accepts, for the sake of argument, that the skilled person might consider that the complete hIL-23 heterodimer was a suitable immunogen to raise the claimed antibodies.

37. It is common ground that in using the hIL-23 heterodimer for immunisation, the skilled person would obtain a pool of antibodies recognising (linear and conformational) epitopes anywhere on the surface of the hIL-23 heterodimer and its subunits, p19 and p40.

38. Moreover, since the generation of antibodies to the claimed epitope on p19 cannot be controlled by using the hIL-23 heterodimer, it is a matter of chance whether the antibody pool comprises an antibody that has the same specificity as the exemplified antibody 7G10 (see point 22. above).

39. Therefore, if the skilled person were to choose the hIL-23 heterodimer for raising antibodies, they would obtain a pool of antibodies, which may or may not comprise antibodies having the required properties.

40. However, the board holds that starting from the above mentioned pool of antibodies, the skilled person would not be able to arrive at the claimed antibodies without an undue burden of experimentation for the following reasons.

Screening antibodies for p19 specificity

41. The appellant submitted that, having raised a pool of antibodies against the hIL-23 heterodimer, the skilled person, seeking to put the claimed invention into practice, would have screened the pool to identify those antibodies that bind an epitope on the p19 subunit using any conventional assay available in the art, e.g. an enzyme-linked immunosorbent assay (ELISA).

42. The board acknowledges that at the priority date of the patent, the skilled person was familiar with ELISAs, e.g., for screening hybridoma supernatants for antibodies that bind to a given antigen. For this, the antigen is offered in an ELISA as a binding partner allowing the selection from a pool of antibodies those candidates that bind the antigen.

43. The patent does not disclose which antigen should be used in an ELISA to screen the pool of antibodies raised by immunisation with the hIL-23 heterodimer to obtain those antibodies that bind a conformational epitope on the p19 subunit of hIL-23 (see paragraphs [0082] and [0084]). The only ELISA mentioned in the patent refers to testing of antibodies "for specificity of binding by comparing binding to IL-23 to binding to irrelevant antigen or antigen mixture under a given set of conditions" (see paragraph [0118]).

44. Document D32, relied on by the appellant as evidence that ELISAs were well known in the state of the art, merely confirms that an ELISA can be set up, provided an antigen suitable to screen for the desired property is available (see page 168, second and third paragraph). However, document D32 provides no information as regards antigens or screening steps, e.g. positive and/or negative, which would be suitable to select antibodies that bind an epitope on the p19 subunit, nor does it address the difficulties in selecting an antibody as claimed from a pool of antibodies raised against hIL-23 and without missing antibodies that bind at p19 in the conformation that this subunit adopts in the presence of p40.

45. Documents D13 and D43, relied on by the appellant to confirm that ELISA tests were commonly used in the field at the priority date, and in the "specific context of determining p19-specificity" are production information sheets for commercially available anti-IL-23p19 antibodies. These documents do not constitute what is commonly understood to represent the common general knowledge of the person skilled in the art (see CLBA I.C.2.8.1).

46. Furthermore, document D13 discloses an anti-p19 antibody that was selected for its ability to neutralise the bioactivity of human IL-23. As regards ELISA tests, document D13 discloses that the selected antibody detects the human IL-23 heterodimer and does not cross-react with rhIL-12 p35, rhIL-12 heterodimer, rmIL-23 p40, or rmIL-23 heterodimer. Document D13 does not disclose that any of these ELISA tests was used for isolating the antibody. As for document D43, it discloses another anti-p19 antibody, which was selected by passing sera from immunised goats over a human IL-23 affinity column and then passing the bound fraction over a human IL-12/23 p40 column to remove p40 specific IgG. However, neither document D13 nor document D43 discloses an ELISA that can be used to screen a pool of anti-hIL-23 antibodies to identify antibodies that bind to p19. A fortiori, these documents are unsuitable to provide evidence that the skilled person could have used a routine ELISA to identify and isolate antibodies that bind a conformational epitope on the p19 subunit of hIL-23.

47. The appellant's further argument that alternatively, or in addition, a routine ELISA could have been used to screen for antibodies that bind to the hIL-23 heterodimer but do not bind to the related hIL-12 heterodimer (which lacks the p19 subunit) or to p40 alone and a conventional bioassay to screen the antibodies for inhibition of IL-23 activity but not IL-12 activity is not found persuasive either.

48. There is no teaching or guidance in the patent that would suggest the use of any of these ELISA assays, nor has the appellant referred to any evidence that they were common general knowledge at the priority date. A fortiori, there is no guidance or information with respect to how these assays would need to be performed and whether they would at all be suitable to reliably identify antibodies that bind a conformational epitope on the p19 subunit of hIL-23.

49. Screening for antibodies inhibiting the biological activity of hIL-23, as also suggested by the appellant, cannot differentiate between antibodies binding to the p19 and the p40 subunit of hIL-23. Therefore, this method is not suitable to specifically select antibodies that bind a conformational epitope on the p19 subunit of hIL-23.

Optional additional pre-screening to narrow down the pool of anti-hIL-23p19 antibodies

50. The appellant's argument that the skilled person could narrow down an initial pool of anti-hIL-23p19 antibodies to a smaller group of candidates by a conventional cross-blocking assay to eliminate antibodies that are unlikely to bind at the claimed conformational epitope is not found persuasive either. In fact, the patent proposes to use such an assay for exactly the opposite purpose, namely "to screen for antibodies that bind to the epitope on human IL-23 (i.e. the p19 subunit) bound by an antibody of interest" (see paragraph [0110]), not to eliminate antibodies that are unlikely to bind.

51. Moreover, the appellant's reasoning for using a cross-blocking assay to eliminate antibodies that are unlikely to bind at the claimed conformational epitope is based on its knowledge of antibody 7G10's footprint on hIL-23. However, this footprint is only disclosed in post-published document D18 (see page 948). Based on the teaching in the patent, the skilled person had no reason to expect that a cross-blocking assay would significantly reduce the number of candidate antibodies in a preselected pool of anti-p19 antibodies.

52. Finally, even if the skilled person were to use a cross-blocking assay to eliminate antibodies unlikely to bind at the claimed conformational epitope, they would be aware that the remaining antibodies will not necessarily bind at the claimed epitope. Indeed the patent confirms that not all cross-blocking antibodies necessarily bind at precisely the same epitope, since cross-blocking may result from steric hindrance (see paragraphs [0110] of the patent).

53. As regards the further strategy proposed by the appellant to reduce a pool of anti-p19 antibodies, the board notes that the patent does not teach that grouping of antibodies based on CDR sequences should be included in the process for identifying antibodies that bind at the epitope defined in the claim. No evidence was presented by the appellant that such an assay represented common general knowledge or was routine for the skilled person. Furthermore, the board has seen no evidence to support the thesis that the probability of finding an antibody with the desired binding properties increases by grouping the candidate antibodies into such sub-classes (see also documents D80, points 20 and 21 and document D81, point 58).

Undue burden

54. It is apparent from the above considerations (see points 41. to 49.) that the evidence on file does not support the appellant's assertion that suitable methods for screening a pool of anti-hIL-23 antibodies for p19-specificity were part of the skilled person's common general knowledge at the priority date. Since the patent provides no guidance in this respect either, the skilled person wanting to perform the claimed invention would have to develop a screening process for identifying antibodies that bind an epitope on the p19 subunit of hIL-23 and without risking to miss antibodies that bind the claimed conformational epitope, an undertaking that cannot be regarded as routine.

55. The appellant's argument that it was a matter of routine for the skilled person to perform further screening and narrow down a pool of p19-specific antibodies to arrive at a subset of antibodies that is "most likely to bind the claimed epitope", is not supported by the evidence on file either. Indeed, none of the screening assays proposed by the appellant selects specifically for antibodies that have the same specificity as the exemplified antibody 7G10 (see points 50. to 53. above).

56. Moreover, as set out above (see points 38. and 39.), there is no guarantee that even a single antibody having the same specificity as the exemplified antibody 7G10 is generated when using hIL-23 heterodimer for immunisation. Therefore, removing antibodies that are unlikely to bind at the claimed epitope, does not guarantee that any of the remaining antibodies is more likely to have the required specificity. Indeed, there is no guarantee that even a single antibody that is taken forward to determine its epitope, by X-RC or otherwise, has the same specificity as the exemplified antibody 7G10.

57. The patent does not provide any information regarding the epitopes recognised by the antibodies raised against hIL-23 heterodimer. In particular, the patent provides no evidence that antibodies having the required properties would be generated frequently enough to be identified reliably. Whilst the appellant submitted that the pool of antibodies raised against hIL-23 heterodimer would be expected to include many p19-specific antibodies that are highly unlikely to bind to hIL-23p19 at either of the epitope regions recited in claim 1, it provided no argument let alone evidence on how likely it was that such a pool of antibodies would include ones that do have the required specificity.

58. In summary, given the lack of relevant guidance in the patent or in the common general knowledge, the skilled person attempting to carry out the claimed invention is confronted with having to develop an elaborate screening strategy, without a reasonable expectation of success. Indeed such a screening strategy relies on chance, without the skilled person having any knowledge of the likelihood of success.

59. Finally, if after such a screening process, the antibody taken forward for epitope determination does not have the required specificity, i.e. in case of failure, neither the patent nor the common general knowledge provides adequate information regarding what should be changed or how to guarantee success.

Conclusion on disclosure of the invention (Article 100(b) EPC)

60. An invention may be regarded as sufficiently disclosed even if it requires a certain amount of experimentation by the skilled person to carry it out, as long as this experimentation is not an undue burden on the skilled person. Such a situation may exist where the skilled person has sufficient information to lead them directly towards success through the evaluation of initial failures. Based on the evidence on file, the board considers that in the present case, critical information on the antigen suitable for raising antibodies with the desired properties and screening assays for reliably identifying them is lacking. Moreover, the board has seen no evidence that antibodies binding at the claimed epitope can be generated frequently enough and can be identified reliably enough to guarantee success (see points 34.

to 59. above). Therefore, the functional definition of the claimed antibody amounts to an invitation to perform a research program without any guarantee of success. Such a situation is considered to amount to an undue burden for the skilled person (see also CLBA, section II.C.6.7 and II.C.7.4).

61. Contrary to the appellant's submissions, the fact pattern of the case under consideration (see points 34. to 53. above) is comparable to the facts underlying the case considered in decision T 1466/05. Thus, also in decision T 1466/05, the claimed antibodies were defined functionally (by their binding activity) and while the application provided one exemplary antibody having this function, it failed to provide (i) the antigen required to raise further antibodies as claimed and (ii) a screening process for the specific selection of the same (see Reasons, points 9 and 25).

62. Disclosure of the specific regions within the p19 subunit of hIL-23 that are comprised in the epitope of the claimed antibodies does not distinguish the case at hand from the case underlying T 1466/05 because it does not equate with disclosure of a suitable antigen that can be used for raising and screening antibodies binding at the claimed epitope by applying routine methodology (see also point 30. above).

63. In the circumstances of the case at hand, serious doubts arise from the verifiable fact that there is no relevant guidance in the patent and in the common general knowledge with respect to (i) an antigen suitable for raising antibodies with the desired properties and (ii) screening assays for reliably identifying them. Contrary to the appellant's assertion, the respondents were therefore under no obligation to provide experimental evidence to support the insufficiency objection.

64. The claimed invention is not sufficiently disclosed in the patent and therefore the ground for opposition under Article 100(b) EPC prejudices the maintenance of the patent as granted.

Auxiliary requests 1 to 49

Disclosure of the invention (Article 83 EPC)

65. Claim 1 of these claim requests is directed to antibodies defined solely by the functional feature of binding the conformational epitope defined therein (see section VI. above). The provision of these antibodies involves an undue burden for the reasons set out in points 23. to 64. above. The invention defined in auxiliary requests 1 to 49 is thus not sufficiently disclosed within the meaning of Article 83 EPC.

Order

For these reasons it is decided that:

The appeal is dismissed.

T 0899/18 - Rat embryonic stem cell

Key points

•  This might be a run-of-the-mill biotech opposition case.
• Claim 1 is directed to: " A rat embryonic stem cell characterized by having the following properties (a)-(j):   [...] (c) having an embryoid body forming ability, (d) expressing SSEA (Stage-Specific Embryonic Antigen)-1 and SSEA-4, (e) having the same number of chromosomes as does a normal rat cell, (f) capable of being subcultured and holding the undifferentiated state, (g) having in vitro pluripotency, (h) having the potential to differentiate into cells of the three embryonic germ lineages, (i) having teratoma formation ability, and (j) having an ability to produce a chimeric rat." 
• Claim 2 is directed to " A method of producing a rat embryonic stem cell " 
• Claim 5 is the product-by-process claim: " A rat embryonic stem cell obtained by the method according to any one of claims 2 to 4." 
• Claim 13 is: " Use of a rat embryonic stem cell of claim 1 or 5 in the production of a genetically modified rat." 
• Claim 14 is: " A method of producing a genetically modified rat, which comprises the following steps (X)-(Z): (X) introducing a desired gene into the rat embryonic stem cell of claim 1 or 5, (Y) preparing an oocyte for transplantation comprising the rat embryonic stem cell into which the gene was introduced, (Z) transferring the oocyte for transplantation into a pseudopregnant female rat to produce an offspring rat.
• Claim 15 is: " A genetically modified rat produced by the production method of claim 14." 
• The opponent appeals only on the ground of insufficient disclosure.
• " The methods and results disclosed in the patent are confirmed by the experimental evidence in document (2), which was produced and submitted by the respondents after the publication date of the application on which the present patent was granted. While the appellant argued that the probative value of document (2) was highly suspect, he did not put forward any persuasive arguments to support his allegation. 
• " In the light of the experimental results provided in the examples of the patent, there is no doubt that chimeric rats produced by the methods taught in the patent are genetically modified, in particular by insertion of the GFP gene into the cell genome in most tissues, including testis (see Figure 24 of the patent). No experimental evidence to the contrary has been submitted by the appellant." 
• The Board: " the evidence in documents (1) and (3) does not discharge the appellant's burden of proof, nor supports his objection of lack of sufficient disclosure of the claimed rat embryonic stem cells." 
• Application filing date 2005.

• EPO 

The link to the decision is provided after the jump.

T 0527/17 - Muscle Derived Cells

Key points

•  Claim 1 is directed to: " A pharmaceutical composition comprising human muscle-derived progenitor cells (MDCs) for use in improving left ventricular contractility of the heart wherein said improving comprises administering the MDCs to the heart of a human subject in need thereof" 
• Claim 3 is directed to: "MDCs for use in administration to the heart of a mammalian subject to thereby improve left ventricular contractility in said subject in need thereof" 
• Claim 3 is interesting in that it implies that human cells can be a "substance or composition" in the sense of Art. 54(4) and (5).
• By way of comparison, the border between compositions and apparatuses (for second medical use claims) is quite a topic of debate.
• " It was a matter of dispute whether the therapeutic indication in claim 1 constitutes an additional difference." 
• " The effect brought about by the differences agreed by the parties [i.e. the undisputed distinguishing features] is that the MDCs of claim 1 are suitable for improving the left ventricular contractility of the human subject from which they have been obtained." 
• " The objective technical problem to be solved may thus be formulated as providing a product suitable for improving left ventricular contractility in a human subject needing it." 
• " The skilled person wishing to translate the therapeutic effect on the myocardium shown in Example 7 of D9 from rodents to humans would therefore be prompted to use human myogenic cells isolated according to the method of D9 and disregard the methods of D5 or Example 9 of D8.

  Hence, the board holds that the subject-matter of claim 1 is inventive." 

• " The opponent did not raise any objection directed specifically against any of claims 2 to 5." 

• EPO T 0527/17

The link to the decision is provided after the jump.

T 1598/16 - Bacteriophage for acne treatment

Key points

•  Claim 1 is directed to: 'A bacteriophage (1) capable of lysing a P. acnes bacterium and incapable of lysing any bacterium which is not P. acnes, and which is incapable of sustaining lysogeny in a bacterium, (2) wherein the bacteriophage has (i) a genome having overall sequence identity of at least 88% with the genome of the bacteriophage deposited under Accession No. NCIMB 41349" (a few alternative deposits follow). [bold text added]
•  " Claim 1 is directed to a bacteriophage defined both by functional features, namely that it is "capable of lysing a P. acnes bacterium and incapable of lysing any bacterium which is not P. acnes, and which is incapable of sustaining lysogeny in a bacterium", and by reference to the accession numbers given to the bacteriophages as deposited with a recognised depositary institution under the Budapest treaty." 
• " The bacteriophages according to the invention are capable of lysing a P. acnes bacterium, incapable of lysing any bacterium which is not P. acnes and incapable of sustaining lysogeny in a bacterium (paragraph [0023]). " 
• "  The opposition division considered document D8 the closest prior art, and no other documents have been put forward in the appeal proceedings. The board agrees that document D8, a meeting abstract disclosing the use of bacteriophages for treatment of acne, is a suitable starting point for the discussion of inventive step. Although D8 does not disclose any particular bacteriophage, it teaches that "Unlike antibiotics, phage are specific for one species of bacteria" and furthermore states that they have isolated several strains of phage which kill subsets of the strain bank comprising a large number of strains of P. acnes and that they "are currently isolating mutants of these phages with exclusively lytic capabilities and broad spectrum of virulence". D8 thus identifies the functional features as claimed, namely species specificity with a broad spectrum of virulence and exclusively lytic capabilities (i.e. no lysogenic capability) as being desirable properties for bacteriophages to be used in the treatment of acne." 
• " The difference between D8 and the subject-matter claimed in claim 1 is that specific bacteriophages, identified by reference to their deposit numbers or by structural features, are not provided in D8. The technical problem can thus be formulated as the provision of bacteriophages which possess the desired characteristics as listed in D8 and are therefore suitable for use in the prevention and treatment of acne. The solution consists of the bacteriophages as claimed, and the board is satisfied that the problem has been solved." 
• "the board considers that the solution involves an inventive step because there is no teaching in the prior art rendering obvious the provision of the three claimed bacteriophages, which are not merely further bacteriophages as they do have properties that render them particularly suitable for the aim of the patent, namely prevention and treatment of acne" 
• As a comment, this decision appears to illustrate that naturally occurring micro-organisms can very well be patented under the EPC. 

EPO T 1598/16

The link to the decision is provided after the jump.

T 2218/16 - Gene therapy and result to be achieved

 Key points

• Claim 1 is a second medical use claim directed to basically an AAV vector comprising a therapeutic gene for use in a method for treating a motor neuron disorder in a subject. The AAV vector is further specified, as well as the mode of administration. The therapeutic gene is defined as “wherein the therapeutic gene is operably linked to a promoter specific or functional in motor neurons”. The claim further specifies a functional feature described below.
• Novelty over D2 is considered. “Document D2 discloses the same scAAV9 vector, therapeutic genes, motor neuron disorders to be treated ...  including the same mode of administration as referred to in claim 1 ... Document D2 further discloses ubiquitous promoters, like CMV ... which as shown in the patent, are functional in motor neurons too.”
• “It was contested between the parties whether or not document D2 discloses motor neurons transfected by the scAAV9 vector.”
• "The claim inter alia specifies that the administration of these vectors cause "infection of spinal cord motor neurons and expression of the gene in spinal cord motor neurons". Accordingly, the claimed use of the scAAV9 vectors is defined by a functional feature that indicates the desired result to be achieved, namely the transfection of spinal cord motor neurons as a necessary prerequisite to achieve a therapeutic effect. According to the case law, functional features are technical features of the claim (see Case Law, II.A.3.4., II.C.7.2.). As set out above, document D2 does not disclose the transfection of motor neurons. Thus, the "result-to-be-achieved" feature in claim 1 relates to a new technical effect."
• “ document D2 is silent on directly transfecting motor neurons, and relates to the transfection of other target cells that, after secretion of a therapeutic product, have an indirect effect on cells involved in the development of particular diseases, inter alia, SMA. The respondents did not dispute that a scAAV9-based therapy that did not directly transfect motor neurons was not suitable for treating SMA. In these circumstances document D2 provides a non-enabling disclosure for the treatment of SMA. Since for the reasons outlined above, the new mechanism of action creates a new clinical situation, the board concludes that the situation in the present case differs from that underlying the decisions T 433/14 and T 406/06.”
• The claims are found to be novel, inventive, and allowable.

T 2218/16 - 

https://www.epo.org/law-practice/case-law-appeals/recent/t162218eu1.html

Claim 1 of the main request reads:

"1. An AAV vector comprising a therapeutic gene for use in a method for treating a motor neuron disorder in a subject, wherein said AAV vector is administered by by intraperitoneal (i.p.), intramuscular (i.m.) or intravenous (i.v.) injection, preferably intravenous injection, to said subject, said administration causing infection of spinal cord motor neurons and expression of the gene in spinal cord motor neurons, wherein said AAV vector is:

- a double-stranded self-complementary AAV9 vector, or

- a pseudotyped AAV vector comprising a double-stranded self-complementary AAV genome derived from an AAV serotype different from the AAV9 serotype and a capsid derived from an AAV9 capsid; and

wherein the therapeutic gene is operably linked to a promoter specific or functional in motor neurons".

Reasons for the Decision

Novelty

40. In a first line of argument, the appellant submitted that the subject-matter of claim 1 lacked novelty over documents D1 and D2. Since, as the appellant further submitted, the disclosure of both documents is "very similar, if not identical", in the following reference will be made to relevant passages in document D2 only.

40.1 Document D2 discloses the same scAAV9 vector, therapeutic genes, motor neuron disorders to be treated (e.g. SMA, amyotrophic lateral sclerosis (ALS), or Kennedy's disease), including the same mode of administration as referred to in claim 1 (see for example page 1, first paragraph; page 6, lines 1 to 3, 17 to 19; page 12, lines 3 to 10 and 15 to 23). Document D2 further discloses ubiquitous promoters, like CMV (see page 9, lines 17, 27 and 28), which as shown in the patent, are functional in motor neurons too. The board is therefore not convinced by the respondents' argument, that document D2 discloses a promoter subset that is different from the "functional" promoters cited in claim 1.