Tuesday, 29 November 2011

T 945/09 – The Patient Who Knew

The opponent filed an appeal against the decision of the Opposition Division (OD) to reject the opposition.

Claim 1 as granted read:
Use of taurolidine or taurultam in the manufacture of a solution for preventing or reducing infection and sepsis in or caused by a delivery system for administration of a desired liquid material to a patient or withdrawal of a blood sample from a patient, wherein said solution is employed to fill the system between each said administration or withdrawal so as to act as an antimicrobial seal serving to prevent or reduce said infection and sepsis.
Document D3, on which a novelty attack was based, is an article published in the Journal of Parenteral and Enteral Nutrition in 1998, i.e. after the earliest priority date of the patent under consideration (December 23, 1996). This article reported on a previous use of 2% taurolidine solutions to fill catheters).

The OD considered that this use did not destroy the novelty of Claim 1 because it was covered by an implicit obligation of confidentiality. According to the OD, the evidence provided by the opponent was not sufficient to establish that there was no such obligation or that it had been violated.

The Board does not come to the same conclusion.

[3.1] In one of the alternative embodiments the claimed subject-matter of the patent in suit relates to
  • the use of taurolidine in the manufacture of a solution
  • for preventing infection and sepsis
  • in a delivery system for administration of a desired liquid material to a patient,
  • wherein said solution is employed to fill the system between each said administration
  • so as to act as an antimicrobial seal
  • serving to prevent said infection and sepsis.
[3.2] Document D3 teaches
  • the use of taurolidine in the manufacture of a solution […]
  • for preventing infection and sepsis […]
  • in a delivery system for administration of a desired liquid material to a patient […],
  • wherein said solution is employed to fill the system between each said administration […]
  • serving to prevent said infection and sepsis […].
The person skilled in the art of total parenteral nutrition at the priority date of the patent in suit knows that the catheter lumen must be sealed during times when it is not used for administration of the nutrient, and refers to it as the lock-technique. This seal may be performed using heparin solution as is referred to in document […].

Thus, the remaining feature
  • so as to act as an antimicrobial seal
is also inevitably comprised in the teaching of document D3.

Consequently, the teaching of document D3 in the form of the reported use of taurolidine solution as a lock represents all the features of claim 1 of the patent in suit.

[3.3] Concerning the question of when this teaching of taurolidine-lock was performed, and in particular when it began to be performed, there is prima facie the clear-cut normal case that a paper is ready before it is sent to a journal for publication and there is normally no need for substantial amendments after the date of receipt. First there is the record of a success, then the idea and realisation of publication follow. In the current case there is evidence for the particular date of receipt at the bottom of page 242 of document D3, left column: “Received for publication, May 28, 1997”.

Since any decision to publish a paper inevitably must lie in the period before its receipt for publication, the authors of document D3 must have decided to publish their experience in the time before May 1997. Following the time frame proposed by the respondent, this would have been just shortly after they had removed the catheter and implemented systemic antibiotic treatment (ten months after March 1996, which was January 1997) - stripped of the experience of a further 12 months free of infection.

According to these considerations, the board is satisfied that the starting date for the use of the taurolidine-lock can be set at 22 months before the date of receipt for publication, i.e. July 1995.

Doubting this normal sequence of actions, under the circumstances of the current case as set out, requires tangible evidence and not just one example of differing experience in another case and statements based on several mere assumptions […]. The maxim “reus in excipiendo fit actor” applies here. The burden is on the respondent to show that the actual facts and their sequence in truth were different.

[3.4] In document D3 it is pointed out that
“Ten months before the last infection, the patient was instructed to instil 1.5 mL taurolidine 2% daily into his central line after finishing his HPN (home parenteral nutrition) infusion and has continued to do so 2 years to date” (parenthesis inserted by the board).
Thus, the teaching according to claim 1 of the patent in suit was used by a patient while having “home parenteral nutrition” (HPN). Such a patient, aged around 30, after his long history of complications leading to multiple replacements of the catheter […] usually knows what is happening to him and he is interested in the nature of all actions intended to bring him relief. In addition, the “evaluation of the patient’s protocol of site care” mentioned in document D3 […] would not have been possible without exact explanation for instance of the purpose of the daily instillation of 1.5 mL of heparin solution. Consequently, it is also to be seen as a prerequisite that the intention connected with the heparin replacement by 1.5 mL of taurolidine solution […] was sufficiently explained to him.

In addition, there is no remark in document D3 indicating anything to the contrary.

Therefore, the board has to base its considerations and conclusions on the knowledge of the patient being clear and concise enough that he could take notice of the technique used after replacement of heparin-lock by taurolidine-lock, representing the teaching of claim 1 of the patent in suit.

There was also no reason for him to treat this knowledge as a secret, because at that time the acting doctors simply tried to apply taurolidine of whatever provenance using a technique they derived freely and easily from the state of the art common to them at that time […]. Obviously, they never saw anything special about that treatment, and consequently there is no indication of confidentiality in document D3.

[3.5] Accordingly, the board concludes that this teaching was performed beginning from July 1995 in the full knowledge of the patient without any obligation of confidentiality and thus was publicly available before the priority date of the patent in suit.

[4] In these circumstances the arguments of the respondent cannot lead to success.

[4.1] To the extent that the respondent calls for standards for a chain of evidence and arguments on the basis of the balance of probability, the board sees the argumentation of the appellant as being based on an indicative document, whereas the respondent itself tries to establish a chain of evidence and arguments to cast doubt on a document which prima facie appears to be decisive. Thus, the required standards have a priori to be applied to the arguments of the respondent.

[4.2] The respondent concludes from the age 29 mentioned at the beginning of document D3 and the following series of episodes of catheter-related bloodstream infections (CRBSIs) and line changes that the letter of authorisation dated 12 March 1996 (document D20b) is related to the same patient mentioned in this letter as “HP” at the age of 30. Since, as reported in documents (12) and (20a), it was the first shipment of taurolidine from the respondent to the Canadian team after a long break, the respondent draws the further conclusion that there were no reserves from the last shipment, and the beginning of the taurolidine treatment of the patient reported in D3 thus could not have started before this shipment of March 1996. Disclosure of document D3 was consistent with this view on the basis of a simple update before printing.

But this chain of various indicia, put together from different documents that are not all known in their full context, together with the attempt to establish the identity of the patient through indirect conclusions, is not well-founded enough to cast doubt on the straightforward starting date of taurolidine-lock treatment of catheter-related bloodstream infections derived from the disclosure of document D3. In particular, the mere statement that there was an amendment of the text of document D3 is not sufficient to make such an event a reality.

[4.3] The fact that the taurolidine-lock treatment at least at the beginning of the last twelve months (“New tunnelled subclavian” from table 1 of document D3) was accompanied by systemic therapy with vancomycin and was maybe in parallel at any time with taurolidine as an additive to the nutritional solution (Ninewell’s method) is irrelevant with respect to the clear intention of the Canadian team to interrupt the pattern of catheter-related bloodstream infections by use of the taurolidine-lock technique. The test was made using the taurolidine-lock and in full awareness of the problems of the patient with regard to repeated sepsis originating from the catheter and with the intention of fighting this problem by using this lock technique […]. Addition of systemic vancomycin occasionally during this episode merely underlines that the lock-technique per se was directed to fight the sepsis originating from the catheter and not systemic sepsis.

Finally, document D3 even reports the authors as being convinced of the success of their use of antimicrobial taurolidine-lock with respect to infection being catheter-related […].

[4.4] Since the respondent no longer maintains its argument that a real confidentiality agreement existed between itself as a supplier of taurolidine and the Canadian team as user, and since it merely affirms that confidentiality was inherent, only this inherency is to be assessed, in particular in relation to the decision of a technical board of appeal cited by the respondent (T 1057/92):

In the cited decision the acting doctor is held not to be an appropriate witness to state what information was public […].
“… In these circumstances, the Board cannot accept evidence that the person carrying out the trials believed that she was making the results available to the public already when carrying out the trials, and not only later when publishing her paper, as evidence that it was indeed made available to the public at the time of the trials. Just because Dr Hedner knew exactly what trials she was carrying out, she is not the appropriate witness to state what, if anything, was made available to the public as a result of the trials. She was not in the position of a member of the public, and thus could only make conjectures about what knowledge the public might have acquired. The Board thus does not take these trials in the hospital on human patients into account for the purpose of assessing novelty or inventive step.”
In the current case, however, it is sufficient that the patient was aware of the treatment he received, and public prior use does not depend on the doctor being a witness. In addition, in the cited decision novelty was discussed with regard to whether a trace of another compound was present or absent (see point [5] of the decision), while in the current case the straightforward use of a compound as such was crucial for assessment of novelty.

Moreover, the action in the Canadian hospital of using the taurolidine-lock was not typical of a clinical or even an experimental approach because it was dictated by the instant necessity to help a patient in a very desperate situation and thus had not been planned systematically as a scientific experiment.

[4.5] Thus, the subject-matter of the sole request does not meet the requirements of A 54.

To download the whole decision, click here.

The file wrapper can be found here.

NB: I owe the knowledge of this decision, which had escaped my scrutiny, to the 2011 FNDE meeting in Lyon.


Anonymous said...

In fact, you didn't miss this case - you reported it on 25 October 2010, and followed up with the petition to the Enlarged Board (R19/10) on 27 April 2011!

oliver said...


I knew this would happen sooner or later.

I should retire before long.

Anonymous said...

For whatever it's worth, the wikipedia entry for the claimed use states:

Taurolidine has been investigated for the prevention of central venous catheter-related infections; while there is positive in vivo and in vitro evidence supporting such an application, the current evidence is "insufficient to warrant routine use of taurolidine".[3]

I sometimes wondered whether I could use the submission date of a paper as its publication date in the sense of Art. 54(2), considering that the intent of the authors is to render the information public starting from the moment it is submitted. But is it accessible? Zat iz ze question. Even though the review process is theoretically confidential and anonymous, it also often happens that the draft is sent straight to the scientist's worst rival, who also happens to be the most qualified person for assessing his work.

For the redux, don't worry. It sometimes happened to me when I was searching prior art that the best document I found was the application itself... Doh...

I was admitted to hospital some years ago, and the toubib came to me proposing to take part in a clinical study for a further medical indication of an already approved composition (a certain brand of low molecular weight heparin). I represented an "ideal case" for the blouses blanches, and was given the consent papers to read and approve. "There I am lying in bed with my fever hardly down from 40 degrees or so, studying a 17 page single-spaced document in German, including the small print for two separate insurance policies. WHAT AM I DOING HERE?" I was already bored, and the risk appeared minimal, so I signed up, out of curiosity about the process. I did ponder about the nature of the disclosure that had taken place, and I would agree that an interested patient is in the position to know what substance is administered to him, and why. (BTW, no patent had been filed for the further medical use. Routine stuff, really).

Some years earlier another drug had been prescribed to me, and the best information I could gather about it (and my condition) were the thousands of pages of evidence filed in the opposition procedure... This is where I discovered that medicine is something more of an art than a science.

Anonymous said...

Anonymous wondered whether the submission date of a paper may be taken as its publication date in the sense of Art. 54(2).

I don't think that is tenable since there is an implicit confidentiality. Both the publisher and the reviewer are in a special relationship to the author, and are not at liberty to quote from the paper before its publication.

The case law book has T 842/91 wherein a book was not only delivered to a publisher but also unrestricted rights of publication were granted. Nevertheless, the book was not considered public until its actual publication.