I. European patent No. 2 697 251, entitled "A method for controlling the main complex N-glycan structures and the acidic variants and variability in bioprocesses producing recombinant proteins", was granted on the basis of European patent application No. 12 713 737.0, filed as an international application published as WO 2012/140138.
II. Two parties filed oppositions, invoking Article 100(a) EPC, in combination with Articles 54 and 56 EPC, and Article 100(b) and (c) EPC, as grounds for opposition.
The opposition division decided to reject the oppositions. Both opponent 1 (appellant I) and opponent 2 (appellant II) appealed this decision.
III. With the reply to the appeals, the patent proprietor (respondent) submitted arguments and claim sets of auxiliary requests 1 to 6, auxiliary requests 1 to 3 being identical to those filed in opposition proceedings.
IV. The board summoned the parties to oral proceedings. In a communication pursuant to Article 15(1) RPBA 2020, it informed them of its preliminary opinion on some of the substantive and legal matters concerning the appeal.
V. Oral proceedings were held by videoconference. At the oral proceedings the respondent maintained its main request and auxiliary request 1, made auxiliary request 5 its auxiliary request 2, filed a new set of claims as auxiliary request 3, and withdrew all other claim requests.
At the end of the oral proceedings, the chair announced the board's decision.
VI. Claim 1 of the main request (patent as granted) reads as follows.
"1. A method of controlling quality and quantity of posttranslational modification of a recombinantly produced polypeptide/protein (glycoprotein), wherein the posttranslational modification is selected from bG0 structures and bG1 structures, and wherein the polypeptide/protein (glycoprotein) production is in eukaryotic host cells, the method comprising the following steps:
a) cultivating the eukaryotic cells in a suitable medium under conditions which allow the expression of the polypeptide/protein, wherein the content of the dissolved CO2 (pCO2) in the medium is at a first value during the initial growth phase of the eukaryotic cells, allowing the eukaryotic cells to grow, and
b) increasing or decreasing the content of the dissolved CO2 (pCO2) in the medium during the production phase of the eukaryotic cells to a second value."
Claim 1 of auxiliary request 1 reads as claim 1 of the main request except for step b), which reads as follows.
"b) increasing the content of the dissolved CO2 (pCO2) in the medium during the production phase of the eukaryotic cells to a second value to increase the amount of bG0 structures and to decrease the amount of bG1 structures, relative to the amounts obtained by a method with no pCO2 regulation, or decreasing the content of the dissolved CO2 (pCO2) in the medium during the production phase of the eukaryotic cells to a second value to decrease the amount of bG0 structures and to increase the amount of bG1 structures, relative to the amounts obtained by a method with no pCO2 regulation."
Claim 1 of auxiliary request 2 reads as claim 1 of auxiliary request 1 except for step b), which reads as follows (differences highlighted by the board, using underlining for additions and strike-through for deletions).
"b) increasing the content of the dissolved CO2 (pCO2) in the medium during the production phase of the eukaryotic cells to a second value to increase the amount of bG0 structures and to decrease the amount of bG1 structures, relative to the amounts obtained by a method with no pCO2 regulation,
wherein the first pCO2 value is set at <=10% and the second pCO2 value is set at >10%
[deleted: or decreasing the content of the dissolved CO]2[deleted: (pCO]2[deleted: ) in the medium during the production phase of the eukaryotic cells to a second value to decrease the amount of bG0 structures and to increase the amount of bG1 structures, relative to the amounts obtained by a method with no pCO]2[deleted: regulation]."
Claim 1 of auxiliary request 3 reads as claim 1 of auxiliary request 2 except for step b), which reads as follows (differences highlighted by the board, using underlining for additions and strike-through for deletions).
"b) increasing the content of the dissolved CO2 (pCO2) in the medium during the production phase of the eukaryotic cells to a second value to increase the amount of bG0 structures and to decrease the amount of bG1 structures, relative to the amounts obtained by a method with no pCO2 regulation,
wherein the first pCO2 value is set in the range of 3.5% to 6.5% [deleted: at <=10%], and the second pCO2 value is set 12% to 35%[deleted: at >10%]."
VII. The following documents are referred to in the present decision.
D1: WO 95/12684
D2: Zanghi et al., Biotechnol. Bioeng., 65(2), 1999, pages 182-191.
VIII. The appellants' arguments, where relevant to this decision, may be summarised as follows.
Main request - Claim 1
Claim interpretation
The core of the invention was the influencing of galactosylation, as also acknowledged by the respondent. Thus, the term "controlling" was to be interpreted as "influencing".
In claim 1, the purpose of the method merely stated the effect that inevitably arose when carrying out method steps a) and b). According to the patent, that purpose was achieved simply by regulating nothing more than pCO2 (see paragraph [0021]), without any additional steps being implied (see paragraph [0022]). There was no indication in claim 1 or in the description that the claimed method contained additional steps. In particular, there was no indication of how "controlling" was to be carried out.
In decision T 1930/14, the board considered such a situation and decided that the purpose of the method was not a limiting feature of the claim. Moreover, the board in decision T 304/08 considered that the purpose of the method as stated in the claim did not imply any technical features. In decision T 1931/14, the board concluded that the purpose stated in a method claim could define an application of a method or, alternatively, the effect inevitably arising from carrying out the method steps. The latter applied to claim 1.
Novelty (Articles 100(a) and 54 EPC)
Documents D1 and D2 disclosed the method steps a) and b) of claim 1, including distinct growth and production phases.
The structures bG0 and bG1 were part of the preamble of claim 1 and therefore not a feature of the claimed method. Thus, in considering the question of novelty it was irrelevant whether the cited prior-art documents disclosed bG0 and bG1 structures. These structures were the result of carrying out the method steps a) and b). Therefore, for the claim to lack novelty it sufficed that these same steps were disclosed in a prior-art document.
Furthermore, the patent and document D1 both used CHO cells, and so the respective methods resulted in identical glycosylation patterns.
Therefore, the subject-matter of claim 1 was not novel in view of each of documents D1 and D2 (see document D1, page 5, lines 4 to 8 and the whole of example 1, in particular on page 10, line 35 (CHO cells), page 13, lines 12 to 15 (CO2 during growth phase), page 14, lines 18 and 19 (CO2 during production phase)).
Contrary to the respondent's argument, the wording of claim 1 did not require the culture medium to be the same in steps a) and b). Furthermore, feeding solutions were used in the patent (see example 3). This amounted to a change in the medium.
Auxiliary request 1 - Claim 1
Novelty (Article 54 EPC)
The respondent had not argued that the additional feature was a further limitation of the method steps.
This feature defined the result of the increase in pCO2 and was not limiting, for the same reasons as submitted for the purpose stated in claim 1 of the main request. Consequently, claim 1 was not novel in view of the disclosure in each of documents D1 and D2.
Auxiliary request 2 - Claim 1
Admittance into the appeal proceedings
There was no substantiation in the written proceedings as to why this request overcame the objections under Article 54 EPC. Moreover, in the context of Article 83 EPC, the passage in the reply to the appeals that was referred to by the respondent did not provide a substantiation of this request either.
Auxiliary request 3
Admittance into the appeal proceedings (Article 13(2) RPBA)
Admittance of this request was governed by Article 13(2) RPBA, which required exceptional circ*mstances. No exceptional circ*mstances had been put forward. Nor were there any, since the objections under Article 54 EPC were present from the outset of the appeal.
For the purpose of procedural economy, and given the complexity of new issues raised, the request should not be admitted into the proceedings. The new features represented a selection from the ranges specified in dependent claim 5 of the patent as granted. The combination of these selected ranges with an increase in pCO2 had not previously been present in the claims. Claim 1 did not comply with the requirements of Articles 123(2) and 84 EPC.
IX. The respondent's arguments, where relevant to this decision, may be summarised as follows.
Main request - Claim 1
Claim interpretation
The core of the invention was that galactosylation could be influenced by pCO2. The purpose stated in the claim required the bG0 and bG1 profile to be determined and controlled. These steps of determining and controlling were implicit in the claim. Therefore, the purpose of "controlling the quality and quantity" was a feature of the method defined in claim 1.
Paragraph [0021] of the patent did not support the appellants' interpretation of the claim, since it referred to "regulating" the parameter pCO2, and thus used a term similar to "controlling". Controlling of processes generally required adapting the process parameters in order to obtain the desired result, in the present case a desired glycosylation profile.
As in the case underlying decision T 1931/14, the purpose of the method implied method steps in addition to the steps recited in the claim. The claim was directed to a method of controlling and not to a method of production.
Novelty (Articles 100(a) and 54 EPC)
Claim 1 was novel over the disclosure in each of documents D1 and D2, for the following reasons.
These documents did not disclose proteins displaying bG0 and bG1 structures.
Additionally, neither of these documents disclosed that method steps a) and b) were both carried out in the same medium. On the contrary, in both documents the method involved a complete exchange of the medium between steps a) and b). This was to be distinguished from changes to the medium caused by addition of feed, as in example 3 of the patent. Since claim 1 referred in step b) to "the medium", it required the medium to be the same in steps a) and b). Therefore, the claim was novel.
As regards document D2, there was no disclosure of a recombinant protein or of a distinction between a growth and a production phase. These were additional differences from the method in claim 1.
Auxiliary request 1 - Claim 1
Novelty (Article 54 EPC)
The additional feature further defined the steps of controlling. These should be taken into account as steps of the method defined in claim 1. Since these steps of controlling were not disclosed in documents D1 and D2, claim 1 was novel.
Auxiliary request 2
Admittance into the appeal proceedings
This request was filed in response to the objection under Article 83 EPC in the statement setting out the grounds of appeal of appellant II (see pages 19 to 20).
The reasons for filing the request were provided with the reply to the appeals (see page 3, point 2, last sentence).
Auxiliary request 3
Admittance into the appeal proceedings (Article 13(2) RPBA)
The features added to claim 1 of this request were present in claim 5 of the patent as granted. The claimed method included two distinct set values for pCO2. The higher-ranking requests also included different set values for the growth and production phases, so this feature did not give rise to new aspects not yet discussed.
X. Appellant I and appellant II requested that the decision of the opposition division be set aside and the patent be revoked in its entirety.
The respondent requested that the decision of the opposition division be upheld and the patent be maintained as granted (main request), or, alternatively, that the patent be maintained in amended form on the basis of the claim sets according to auxiliary requests 1 to 3, wherein auxiliary request 1 was filed with the reply to the appeals, auxiliary request 2 was filed as auxiliary request 5 with the reply to the appeals, and auxiliary request 3 was filed during the oral proceedings.
