T 0670/20 - Non-analysis clauses and clinical trials

Key points

•  This post is from stock. 
• Documents D19 and D20 relate to phase IIa and phase IIb clinical trials in which patients received treatment .... involving administration of edoxaban for a period of up to ten days. Document D21 (see page 15, line 8) indicates that the edoxaban formulation under investigation during the clinical studies described in documents D19 and D20 [has all the features of claim 1 directed to the pharmaceutical formulation].
• The clinical trials were carried out before the filing date of the patent, the priority being invalid.
• "the appellants [opponents] relied [] on the provision of the tablets under investigation during the trials of documents D19 and D20 to the participating patients who were discharged from hospital before the end of the treatment period. This provision of the tablets to the patients discharged from the hospital before the end of the treatment was not contested by the respondent [proprietor].
• "The assessment of the ground of lack of novelty in view of the trials described in documents D19 and D20 therefore crucially depends 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 clinical trials of documents D19 and D20 were carried out in accordance with the EMEA Guidelines for Good Clinical Practice (document D33). These guidelines explicitly require adherence to the prescribed protocol"
• "This set-up of the trials of documents D19 and D20 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 acknowledges 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. In fact, a duty of confidence regarding such information could be considered to constrain the patients in their ability to freely decide on participating in the trials on the basis of their informed consent, which would seem contrary to the above mentioned guidelines (see document D33, section 4.8). However, the Board finds 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 as explained in section 4.3 above."
• "The Board notes, 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 possibility of non-compliance to the instructed use and return of the tablets by the participating patients does not affect the essence of this agreement. Moreover, the appellants' estimation regarding the likelihood of full compliance remained speculative and therefore without consequence."
• Turning to inventive step (over other documents): " the Board considers that ...the problem to be solved may be formulated as the provision of a solid pharmaceutical composition comprising edoxaban as active ingredient which allows for excellent dissolution properties."
• " the cited prior art provided the skilled person with no reasonable expectation that the use of a combination of a sugar alcohol with pre-gelatinized starch or crystalline cellulose as a water-swelling additive allowed the dissolution of tablets comprising edoxaban to be still further enhanced by coating the tablet with a coating agent as defined in claim 1 of the main request. On the contrary, as indicated in document D23 tablet coatings were expected to have a detrimental effect on the dissolution properties or, in case of thin water-soluble polymers, to have at best no particular effect on dissolution rate of the tablets "
• "the Board agrees with the decision under appeal that the subject-matter of claim 1 of the main request also involves an inventive step."
  
  
• Kudos to the lawyer who added the clause in the protocol. 

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/t200670eu1.html

4. Novelty

4.1 Documents D19 and D20 relate to phase IIa and phase IIb clinical trials in which patients received treatment for the prevention of venous thromboembolism following hip surgery involving administration of edoxaban for a period of up to ten days. Document D21 (see page 15, line 8) indicates that the edoxaban formulation under investigation during the clinical studies described in documents D19 and D20 was the same as the formulation used for marketing. This formulation consisted of a tablet core of edoxaban tosilate with mannitol, pregelatinised starch, crospovidone, hydroxypropylcellulose and magnesium stearate and a film coating from hypromellose, macrogol 8000, titanium oxide, talc, carnauba wax, iron oxide yellow and iron oxide red (see D21, page 11, section 2.2.1).

It was not in dispute that the clinical trials described in documents D19 and D20 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 main request.

4.2 The appellants did not contest that the investigators involved in the trials were, as suggested in documents D31 and D32, 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 appellants did further not contend that the participating patients had actually been directly informed of the internal structure of the tablets under investigation.

Instead, the appellants relied with reference to document D29 (section 4.5.4) and document D30 (see section 5.1) on the provision of the tablets under investigation during the trials of documents D19 and D20 to the participating patients who were discharged from hospital before the end of the treatment period. This provision of the tablets to the patients discharged from hospital before the end of the treatment was not contested by the respondent.

The assessment of the ground of lack of novelty in view of the trials described in documents D19 and D20 therefore crucially depends 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.

4.3 Documents D29 and D30 represent the clinical trial protocols for the studies disclosed respectively in documents D19 and D20. According to document D29 (see sections 4.5.4 and 4.7.2.3) and document D30 (see sections 3.10 and sections 5.1 and 5.5) the investigators in the trials of documents D19 and D20 were instructed to ensure drug accountability and to monitor treatment compliance by taking account of the unused medication returned by the patients discharged from hospital.

As further pointed out by the respondent and not contested by the appellants the clinical trials of documents D19 and D20 were carried out in accordance with the EMEA Guidelines for Good Clinical Practice (document D33). These guidelines explicitly require adherence to the prescribed protocol (see D33, sections 2.6 and 2.12) and assurance of drug accountability (see D33, sections 4.6.1, 4.6.5 and 4.6.6).

This set-up of the trials of documents D19 and D20 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.

4.4 The appellants 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 appellants 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 Board acknowledges 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. In fact, a duty of confidence regarding such information could be considered to constrain the patients in their ability to freely decide on participating in the trials on the basis of their informed consent, which would seem contrary to the above mentioned guidelines (see document D33, section 4.8).

However, the Board finds 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 as explained in section 4.3 above.

4.5 The appellants 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 Board notes, 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 possibility of non-compliance to the instructed use and return of the tablets by the participating patients does not affect the essence of this agreement. Moreover, the appellants' estimation regarding the likelihood of full compliance remained speculative and therefore without consequence.

4.6 In T 7/07 the competent board concluded 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 (see section 3.3, pages 17-18, bridging paragraph, and section 3.6, page 22, lines lines 5-11). In view of the explanations in sections 4.3-4.5 above the Board considers that in the present case the tablets were not provided to the participants of the trial as members of the public, which distinguishes the circumstances of the trials of documents D19 and D20 from the circumstances of the trial considered in T 7/07.

4.7 Accordingly, the Board agrees with the finding in the decision under appeal (see page 22, lines 1-3) that the public did not gain access to the claimed tablets during the trials reported in documents D19 and D20 and that the main request therefore complies with the requirement of novelty.