Pacific Biosciences of California, Inc v Oxford Nanopore Technologies Ltd & Anor

This is an application by the defendants, Oxford Nanopore Technologies Limited ("ONT") for an order compelling the claimant, Pacific Biosciences of California Incorporated ("PacBio") to answer a request for further information, made in late February, and the subject of the application issued on 1st March.

The case is far advanced. Expert evidence was meant to have been exchanged on 27th February; but by agreement between the parties, it is not expected to be exchanged before 28th March. As matters stand, reply expert evidence is the subject of an order that it should be delivered on 3rd April; but I understand that an agreement either has been reached or is expected to be reached between the parties that it shall be served on 17th April. A pre-trial review has been set for a period commencing on 18th April, and the trial itself is due to start on 8th May.

Within this context, clarity in the case

to be addressed in the expert evidence and in the reply evidence,

to be defined in a statement of issues for the PTR, and then

to be debated at trial,

The case concerns sequencing of DNA. I have been taken, in the simplest of terms, to the processes that are involved. Double-stranded DNA consists of two connected polynucleotide chains, with the top strand mirroring the bottom strand. These two strands are connected by hydrogen bonds. PacBio has a process for sequencing double-stranded DNA. It synthesizes a DNA chain, and it then adds a “hairpin” linker to one end of the double strand, so that on the outside there is, in effect, a continuous strand that can be read along the bottom strand, through the linker, and back on to the top strand; both strands being bonded together whilst this sequencing takes place.

As it was put in one of the descriptions I have read in the papers, the strands are linked by way of contiguous nucleotides connected by covalent bonds. This is the subject of European Patent UK No. 30045542 (the '542 patent) of which there is a divisional, but for present purposes, I can simply look at the '542 patent.

Claim 1 of the patent speaks of a method of generating nucleotide sequence data for a nucleic acid sequencing template, comprising providing a nucleic acid sequencing template comprising a double-stranded portion, a double-stranded portion comprising two nucleic acid strands that are complementary to each other and are linked at one end by “a connecting nucleic acid” that links a 3' end of one strand of the two nucleic acid strands to a 5' end of another strand of the two nucleic acid strands and performing a single molecule sequencing process on the said nucleic acid sequencing template, thereby generating nucleotide sequence data for both of the said two nucleic acid strands of the said nucleic acid sequencing template. (I have emphasised the key part of the claim for the purposes of the issue before me).

ONT has developed its own sequencing process for double-stranded DNA, by separating the two strands of DNA and separately sequencing each strand, by passing them through a nanopore in a membrane, and by recording variations in the electric current as each strand passes through the nanopore. These two results can then be compared in order to produce an accurate record of one strand of the DNA. This process it calls 1D². To achieve this result, it uses adapters which are inserted into each strand of the DNA. I will have to explain in a little more detail the importance of this when I come to the nature of the dispute.

ONT sought, first, an acknowledgement, by PacBio, that this technique did not infringe patent '542. After some tactical skirmishing, which I do not think relevant to anything I have to decide today, on 27th November 2017, ONT counterclaimed for a declaration of non-infringement, to which PacBio responded defensively, but then on 23rd February 2018, responded positively by alleging infringement, notwithstanding the apparent absence in the ONT process of the connecting nucleic acid which the part of the patent, (claim 1 which I have read) placed emphasis upon.

This state of affairs resulted in an agreed order whereby PacBio would set out its infringement case, which it did in a document entitlement "Statement of case on infringement of the 1D² process". This dealt with two separate cases. The first was a case of literal infringement of patent '542, construed according to ordinary standards of construction. It focused on the part of the claim which I have read out and says that the adapters are connecting nucleic acids. However, there was a second aspect to the infringement claim, based on infringement by equivalence. This was set out in paragraphs 51 following of the statement of case.

This, of course, was a reference to the sort of infringement that was ruled upon in Actavis UK v Eli Lilly [2017] UKSC 48, discussed by Lord Neuberger, from paragraph 53 onwards, and resulted in the identification of three questions to be asked, for a case of infringement by equivalence to be made good.

The language in which the questions were framed was acknowledged to need adaptation to the specific facts of a particular case, but broadly, the reformulated questions were, firstly, whether, notwithstanding that an act was not within the literal meaning of the relevant claims, does the variant used by the defendant achieve substantially the same result in substantially the same way as the invention, i.e., as the inventive concept revealed by the patent?

This would require one to identify the inventive concept revealed by the patent, to identify the variant which the defendant utilises, to identify whether that variant achieves a particular result and to identify the way in which that result is achieved.

The second question then focuses on the result that has been achieved and on the way it is achieved. It poses the question, whether it would be obvious to a skilled person in the art, reading the patent at the priority date, that it did achieve substantially the same result in substantially the same way; the focus of the question being whether the way is obvious.

Then the third question is whether a reader of the patent would have concluded that the holder of the patent had none the less intended that strict compliance with the literal meaning was an essential requirement for the invention.

It is this case, based on equivalence, to which the request for further information is assessed. The ONT process requires that each end of a double strand of DNA must have a sequencing adapter. This is a block of five bases on the bottom strand, which pair with complementary bases on the top strand, using a bond that is slightly stronger than the normal hydrogen bond, though the degree of “stickiness” may be one of the matters that requires examination.

The stickiness is produced by bridged nucleic acids, or BNAs. Shortly put, the function of the BNAs is to stop the double sequence fraying until such time as the top strand of the double-stranded DNA has been inserted (through the passage of ions through the nanopore) into the nanopore and, at that point, to cause the bond between the two strands to disintegrate, allowing the top strand to pass through the pore, and then for the ion current to drag the lower strand through the pore after a short break.

The claimant’s case on equivalence says that although, contrary to the argument on literal construction, the BNAs are not “connecting nucleic acids”, they are the equivalent of the “hairpin” linker, so PacBio will have to address the questions I have identified as being reformulated in Actavis.

It is all very well to say that the ONT process has elements which are ”the equivalent of the connecting nucleic acid”, but how is this to be proven at trial? What evidence will be led? Will it be the case that no evidence at all is led and there will be a simple reliance upon the face of the patent and the face of the product and process description that has been provided by ONT? Or will the claimant call an expert who will say that the BNAs are the equivalent of the connecting nucleic acid, simply because he says so? Or will the claimant call an expert who points to particular facts and then gives his opinion on equivalents, based on those facts? If the expert is going to refer to facts, what facts are they?

It is this, in my judgment, that lies behind the request for further information. A request for further information, under CPR 18, arises really as part of the responsibility of the court to manage cases and the parties to co-operate in the just and efficient disposal of the issues between them. The function of a request is to identify the material facts that are going to be relied upon at trial, but not to plead evidence that will be led to prove those facts. The identification of the material facts, ideally, ought to be with the same degree of particularity as will be relied on at the trial itself. That way, everyone knows where they stand.

A major objective of case management is to ensure that statements of case do set out the parties' cases, and define the dispute between them. As part of its responsibility for managing cases, the court must ensure that parties plainly state the factual ingredients of their case, so that the true nature and scope of the dispute can be identified. I read from paragraph 18.0.1 of the White Book.

Defining issues has, I think, two aspects. First of all, identifying what will be debated and, secondly, eliminating what will not be debated. The second aspect is every bit as important as the first. It is essential that by 8th May, each expert will have addressed the same issues and will only have addressed those issues that are relevant to the cases on either side.

Defining issues for trial and issues to which the evidence must be directed, by means of statements of case, is not the only method of doing it. Sometimes, it is better to say that the parties must agree the terms of, for example, the instructions that are to be sent to experts, but this case is too far down the line for that to be done.

Therefore, the question is whether it is necessary for the just and efficient disposal of this case that there should be some further definition on the claimant's side of the nature of the case on equivalence.

I should note that the defendants have accepted that there should be some further definition of particular aspects of their Defence, in particular relating to the BNAs, which ought to be the subject of further information which is to be provided today or tomorrow.

The defendants' request for further information, launched on 1st March, seeks particulars of paragraph 52 of the statement of case on infringement. The statement of case uses words of generality; the claimant either generally reserving the right to rely on further information or describing the information on which it intends to rely without prejudice to its potential reliance on other matters.

The first request asks the claimant to identify any further matters upon which it intends to rely, other than those specifically mentioned in inclusive terms in the pleading itself, or to confirm that no further matters are to be replied upon.

The genesis of the words of generality was, the claimant says, because there was only piecemeal disclosure by the defendants, the PPD going through several iterations. However, the time has now come, in my judgment, for there to be a snapshot taken of what the claimant says it intends to rely on by way of fact.

If further matters emerge after the exchange of expert evidence, then the claimant must provide voluntary particulars of the additional matters on which it seeks to rely. The question whether those voluntary particulars can fairly be served might have to be addressed, either at the PTR or by the trial judge, but at least one will know that all of the facts on which the claimant intends to rely may be found somewhere in its statement of case on infringement and that there will not be new facts introduced which have not been the subject of consideration by the experts.

The second question reflects the three questions to which I made reference arising out of Actavis. It asks that if the claimant is saying that ONT's sequencing adapters achieve the same result as the connecting nucleic acid referred to in claim 1 of patent '542 in substantially the same way, then the claimant must identify what is said to be the result, what is alleged to be the way in which its connecting nucleic acid achieves that result and what is alleged to be the way in which it is said the sequencing adapter achieves that result. Each of these is, in my judgment, a fair and proper question to be asked for the definition of the case on equivalents.

Paragraph 2(d) of the request asks the claimant to state in what respect PacBio's way and ONT's way are substantially the same, but that, it seems to me, is a request to set out argument, which is not the function, in general, of requests for particulars. I would understand (and would permit) a request which asked what, if any, facts are relied on to establish that ONT's way is substantially the same as PacBio's way, but if no facts are relied on, the matter is simply one for argument.

The third request also reflects those three questions arising from Actavis. Referring to particular allegations which are made in the statement of case, it enquires whether they are directed to the assertion that they demonstrate that ONT's sequencing adapter achieves the same result or whether they are directed to the question whether ONT's sequencing adapter achieves the result in substantially the same way. That is Important for the second question formulated in Actavis.

I regard these as fair and proper questions to ask and which the claimant must answer. They must know what they say is relevant to each of the Actavis questions. But this request goes on to ask PacBio to explain how it is alleged that those facts and matters support the allegation. That, I do not regard as permissible, although undoubtedly helpful, because it in effect asks for argument to be set out in the request for further information.

ONT knows the general nature of the case being advanced. If the proper questions are answered it will know the specific facts that are being relied on in support of that case, and it will know whether those facts are being adduced in relation to question 1, in each of its three limbs, or question 2. That should suffice to enable it to know what case it has to meet.

The fourth request refers to the allegation in the statement of case on infringement, that ONT's sequencing adapter "increases the likelihood that the antisense strand of the double-stranded DNA will interact with the nanopore after the sense strand which thereby enables the generation of the nucleotide sequence data for both of the said strands".

Question 4 asks whether this fact relates to the result which is achieved or to the way in which that result is achieved. Again, I regard that as a fair question necessary to define the issues.

Question 5 relates to one of the general allegations made in the statement of case, demonstrating that the claimant intends to rely on all aspects of the functionality of the sequencing adapter, and seeks that the claimant should identify, in reality, which aspects are relied upon. I regard that as a fair question.

Question 6 asks for the claimant to identify what part of the teaching in the patents is to be relied upon as demonstrating the purpose of the invention, i.e. its inventive core. Although on its face this appears a sensible request, the claimant objects to it, because it is submitted it has not been the practice for over 40 years to permit particularisation of the teaching of the patent, at least so far as construction of the patent according to normal principles is concerned.

However, after Actavis, it seems to me that rather different questions arise and one has to grapple with what counsel for the claimant herself acknowledged were rather difficult-to-grasp questions. She referred to “hand-waving phrases”, which I think captures the difficulty.

In the instant case, I see no difficulty in the claimant identifying those parts of the patent which they say demonstrate its inventive core; a factor which I accept bears upon the question of whether the same result is achieved in substantially the same way for the purposes of the doctrine of equivalence.

Question 7 in the request for information simply asks for clarity as to what certain pleaded words mean and, in general, I accept it as a proper request, but it includes two subbranches to which counsel for the claimant drew attention, expressed as, "and, if so, what the basis for such an allegation is".

I agree that these words are not properly included, since they seek to elicit what argument will be advanced. It would be different, and I would permit a request, if it said, "and, if so, all facts and matters relied on in support of the allegation". In that way, one could be sure that the factual basis was set out and both sides could address it.

Question 8, I would address in largely the same way. It seeks clarity about the nature of the pleaded case, but I do not think it proper that it should include a passage that begins, "in any event, please explain", to the end of the request. This is directed to what is apparently a further or alternative case, which seems to say that the patents are about obtaining data from both strands to increase sequence accuracy, i.e. that any technique or process which obtains data from both strands of the DNA and compares them to produce a single accurate sequence, is somehow within the scope of the patent.

“What is the pleaded case?” is a question that does need to be answered, if it really is what the claimant is saying. However, if it is not what the claimant is saying, I do not see that any further particularity is required; and if it is what the claimant is saying, then what is said seems to be perfectly straightforward and not to require any greater level of particularity.

Therefore, the form of the para 18 request is, itself, in my judgment, subject to those modifications, a proper one that might correctly be served. The question is whether, as a matter of discretion, I ought to order answers to such a request.

The claimant says that it is, in essence, pointless to do so, because their expert evidence will, under the agreed timetable, be served on 28th or 29th March, and the answer to the request for further information will also be served that day so that, in essence, the defendants will not have the assistance of an answer to the RFI when preparing their expert evidence-in-chief.

Whilst that is true, in my judgment, expert evidence and particularity in the statement of case serve two different functions. The function of the expert evidence is not to advance a claimant's case. The function of the expert evidence is to provide opinion evidence, agreeing or disagreeing with allegations which are contained in the claimant's case. It is important that the distinction between the two is maintained.

The fact that expert evidence will be served at or about the same time as the request for further information is, in my judgment, not a determinative factor. I shall, therefore, order the claimant to answer the request for further information in the form in which I have approved it. The parties are agreed as to the timetable which will apply in the event that the request has to be answered.

The defendants have been successful in their application. The normal rule is that the defendants should have their costs. Before making an order in those terms, I am required to consider the other factors set out in CPR 44.3, to see whether a departure from that general rule is justified.

I do not consider that there is anything in the conduct of the defendants or in relation to any of the other factors set out in CPR 44 that would cause me to depart from the general rule.

I shall therefore order that the claimant shall pay the defendants their costs of and occasioned by this application.