The patent relates to a pharmaceutical composition (edoxaban) useful as an anticoagulant, which comprises a component that is improved in dissolution property.
Brief outline of the case
The patent was maintained by the OD according to a MR.
Both opponents appealed the decision.
The board considered that claim 1 as maintained was novel and inventive, although the priority was not valid.
In order to come to a positive assessment of the N, the board considered that participants to clinical tests were not members of the public.
Claim 1 of the MR was also considered inventive and the appeals were dismissed, i.e. the patent maintained according to the MR. When assessing IS the clinical trials were not taken into account.
Novelty and the clinical tests
It was not in dispute that clinical trials had started before the priority date claimed for the patent and that the trials concerned edoxaban tablets which were covered by the definition of claim 1 of the MR.
Clinical trials were described in documents D19 and D20 relating respectively to phase IIa and phase IIb clinical trials.
Tablets were provided to the patients discharged from hospital before the end of the treatment. This was not contested by the proprietor.
Opponents’ point of view
The opponents did not contest that the investigators involved in the trials were bound to confidentiality and could therefore not be considered as part of the public that had access to information regarding the internal structure of the used tablets.
The opponents did further not contend that the participating patients had actually been directly informed of the internal structure of the tablets under investigation.
The opponents argued that the patients participating in the trials were not bound by any confidentiality agreement, which was evident from the statements in documents D19 and D20 that patients were encouraged to discuss their participation with their doctor, relatives and friends (see D19/D20, under “Eligibility Criteria”).
According to the opponents it would actually be unethical to bind a patient to a duty of confidence that prevented them from discussing the trial with their doctor, family members or friends.
The opponents further argued that the patients may have been requested to return unused tablets, but that in the absence of any legal sanction no parallel to a confidentiality agreement could be assumed on such basis, especially as full compliance by all patients would not be likely.
The opponents brought forward T 7/07 which also dealt with clinical trials which were carried out before the priority date.
The board’s considerations
The assessment of the ground of lack of N in view of the trials described in documents D19 and D20 crucially depended on whether the participating patients who received the tablets are to be considered as members of the public who were free to dispose over the provided tablets and thus theoretically in a position to investigate the internal structure of the tablets.
The board held that the clinical trials were carried out in accordance with the EMEA Guidelines for Good Clinical Practice. These guidelines explicitly require adherence to the prescribed protocol and assurance of drug accountability. This set-up of the trials implies that the patients who decided to participate in the trials agreed, following their informed consent, to use the provided medication according to instruction or to return the unused medication.
Accordingly, the participating patients who were provided with the tablets under investigation entered into a special relationship with the investigators of the trials and were with regard to the provided tablets not members of the public that could freely dispose over these tablets.
The board acknowledged that the statements in documents D19 and D20 encouraging patients to discuss their participation in the trials indicates that the patients were not under a duty of confidence with respect to their participation to the trials and the information regarding the trial provided to them in that context.
The board found no reason why the absence of the patients’ duty of confidence with respect to the information relevant to their participation in the trials should affect the obligations of the participating patients regarding the use and return of the tablets provided to them, which resulted from their decision to participate in the trials.
The board noted, however, that the patients’ agreement to use the provided medication according to instruction or to return the unused medication obliges the patients irrespectively of any sanction on non-compliance and therefore disqualifies the patients as members of the public with respect to the medication provided to them.
The present board dismissed the argument based on T 7/07 in that it was of the opinion that in T 7/07 on the basis of the available information that apparently the sponsor of the trial had effectively lost control over the drugs after these had been handed out to the participants of the trial as members of the public who were not bound to secrecy.
In view of the evidence submitted, inter alia redacted protocols of the clinical tests and confidentiality agreements, the board concluded like the OD that the clinical tests were not public, contrary to what the opponents asserted.
In T 7/07, the proprietor did not contest that clinical trials were carried out prior to the priority date and that the principal investigators but not the participants entered into confidentiality agreements.
In T 7/07 the proprietor further argued that the drug had not become publicly available before the priority date as according to established board of appeal case law any persons involved in clinical trials are (implicitly) bound to confidentiality. The board denied that this case law existed in the generality asserted by the proprietor. .
In T 7/07, applying G 1/92 (OJ EPO 1993, 277), the board concluded that the composition of the product under trial was publicly available and therefore was not any longer novel.
Whilst it has been acknowledged in T 7/07 that not all of the unused study drugs were returned, nothing like this is known in the present case. On the balance of probabilities, it is difficult to consider that all the patients returned the unused tablets.
In the present case the patients where encouraged to discuss their participation to the clinical trial with their doctor, relatives and friends.
It is therefore difficult to reconcile that on the one hand the present board considered the participants were not being bound by a secrecy agreement, even if it was about the participation to the trial, but on the other hand they were not members of the public because they were meant to have returned the unused tablets.
We have here again on the same basis two apparently totally different approaches to clinical trials carried out before the priority/filing date of the patent.
In this respect T 158/96, cf. the catchwords, in which phase I trials were mentioned in the prior art appears more convincing.
I would not say that a referral to the EPA is due, but it appears that not only on procedural matters, but also in matters of substance, boards are quite diverging in their views. This not enhancing reliability and predictability.
While preparing the present post, I remembered seeing a decision which was related to the present situation. I could not find it at the time. I have now found it following the comments made.
In T 239/16, the situation was similar to the present one. There was a clinical study in which patients participated without any obligation of confidentiality.
The essential question to be answered was therefore whether the recipients of D 55 = “Information for the patient concerning the study 42446 02 041” were to be considered members of the public within the meaning of Art 54(2). D55 was addressed to a number of patients suffering from osteoporosis who were asked to participate in said study.
D 57 was an affidavit signed by Prof. Verbruggen who was a clinical investigator for Novartis study 42446 02 041 and who followed a number of patients during the study.
It has not been argued by the proprietors that there was an explicit confidentiality agreement between the study sponsor and these patients or an obligation to maintain confidentiality (under national law).
For the board it remained to be seen whether there existed a special situation or some special relationship between the sponsor of the study and the patients having the consequence that the patients, as recipients of the information provided in D 55, could not be considered members of the public due to an implied obligation to maintain confidentiality.
From the information that can be gained from the affidavit it was clear that the patients participating in the study were actively encouraged to discuss the contents of D 55 with “anyone” including their family and family doctor.
For the board in T 239/16, it was established case law that if a single member of the public who is not under an obligation to maintain secrecy has the possibility to access particular information, this information is considered as being available to the public within the meaning of Art 54(2).
In view of the fact that D 55 was handed out to people who were encouraged to discuss its contents with anyone, the board came to the conclusion that the contents of D 55 have been made available to persons neither being bound by any confidentiality agreement nor being in a special relationship to the study sponsor who are thus to be classified as members of the public.
There was no apparent obligation to return unused medicaments. As soon as patients are allowed to discuss the study with anyone including their family members or their family doctor, they are members of the public.
T 670/20 is thus in clear contradiction with T 239/16.
The fact that unused medicaments had to be returned does not allow to exclude patients participating to the study from being members of the public. This is the more so since no proof of this return has been given by the proprietor.