The Evidence
45 ICOS relied on three affidavits sworn by Mr Gary Baxter Cox, lawyer and patent attorney, an affidavit sworn by Dr Mark Jordan Stewart, patent attorney, an affidavit sworn by Mr Danny L Wood, patent attorney, and an affidavit sworn by Dr Malcolm Ian Mitchell, formerly Medical Director at Lilly. None of these witnesses were required for cross-examination.
46 Mr Cox is and has been a principal of Wrays Patent & Trademark Attorneys for about 20 years and Wrays Lawyers for about four years. He is the chairman of Wrays, Patent Attorneys and Wrays Lawyers (Wrays). He has practised in the area of intellectual property and, in particular, patent litigation for approximately 20 years. He has conducted numerous complex trials before the Court concerning the infringement and validity of pharmaceutical patents.
47 On 15 January 2016, Ms Arleen Palmberg, Lilly's assistant general counsel, engaged Wrays to advise Lilly in respect of a potential dispute with Apotex concerning Lilly's sale of Cialis. On 12 February 2016, Ms Palmberg sent a copy of the NOC decision to Mr Cox by email. Mr Cox outlines the details of that proceeding in his affidavits.
48 Mr Todd Shand is a registered patent attorney and a principal of Wrays Patent Attorneys. Between 12 February 2016 and 24 February 2016, he raised with Mr Cox the possibility of amending the 946 Patent in light of the findings in the NOC decision and the benefits to ICOS of doing so.
49 On 24 February 2016, Mr Cox and other members of the Wrays team discussed a number of matters with Ms Palmberg, including the NOC decision. During the course of the telephone conversation, Mr Cox raised for the first time with Ms Palmberg the possibility of amending the 946 Patent in light of the findings in respect of utility in the NOC decision. Thereafter, Mr Cox's attention was directed towards considering infringement and invalidity issues with respect to the 666 Patent, the 946 Patent and the 722 Patent.
50 As I have said, Apotex commenced its proceeding on 4 April 2016. On the following day, ICOS retained Wrays Lawyers to act as its legal representative.
51 On 15 April 2016, there was a further discussion about the NOC decision between the Wrays team and Ms Palmberg and, on this occasion, Lilly's external Canadian lawyers. I have already summarised the nature of the NOC proceeding. Thereafter, Mr Cox took steps to clarify with Apotex the precise way in which it put its case with respect to the alleged lack of utility. I do not need to detail those steps.
52 Wrays became aware of the decision in Actavis Group v ICOS shortly after it was handed down on 10 August 2016 and, unprompted by ICOS or Lilly, Wrays gave consideration to whether the validity of the 666 Patent could be strengthened by amendment.
53 On 31 August 2016, Mr Cox and other members of the Wrays team had a telephone conversation with Dr Mitchell. Mr Cox understood from that conversation that tadalafil could be safely administered to patients who were also being given organic nitrates.
54 By late August or early September 2016, Mr Cox had formed the opinion that ICOS may benefit from amending the 946 Patent to remove statements in the specification concerning the side effect profile of tadalafil when co-administered with organic nitrates. He had a number of communications with Ms Palmberg during September 2016. On 23 September 2016, he had a telephone conference with Ms Palmberg and Dr Stewart. He explained the rationale for the proposed amendments to the 946 Patent. Mr Cox said that it was his understanding that Dr Stewart believed that ICOS could successfully defend Apotex's utility case without the amendments by relying upon clinical results and evidence to be adduced from clinicians. However, Dr Stewart accepted that the amendments, if allowed, would strengthen ICOS' position because the utility issues would be avoided altogether. Mr Cox also explained to Dr Stewart that there was some uncertainty as a result of the decision in Ronneby Road v ESCO, as to whether by Australian law, a claimed invention must satisfy all or only one of the promises made in a patent specification in order to be valid. Dr Stewart instructed Wrays to proceed with the application for the amendments.
55 In relation to the 666 Patent, Mr Cox believed that the validity of the patent could be strengthened by inserting dependent claims that included integers relating to specific doses or dose ranges of tadalafil. Mr Cox believed and continues to believe that the existing claims of the patent are valid without any amendment. However, he formed a view that the addition of further dependent claims featuring doses of tadalafil could only strengthen the validity of the patent and, in particular, the claim that it involved an inventive step. As with the 946 Patent, Wrays received instructions to proceed with the proposed amendments on 23 September 2016.
56 Dr Stewart joined Lilly in 1997 and since 2010, has been a senior director in the Patent Division at Lilly. Dr Stewart has qualifications in science and law and has been a patent attorney since 1998. Between 2010 and 2015, Dr Stewart's primary responsibilities included overseeing various patent litigation and patent procurement activities in the United States and Europe. This has included patent infringement and validity challenges in a number of different courts in Europe and the United States, and patent preparation and prosecution, and offensive and defensive opposition proceedings. In 2015, Dr Stewart's responsibilities expanded to include patent litigation matters all over the world.
57 Since 2014, Dr Stewart has overseen all patent litigation in relation to Cialis in all jurisdictions in the world. He states that internal Lilly patent counsel who support or who have had responsibility for patent litigation in relation to Cialis in various jurisdictions in the world report to him.
58 Dr Stewart has the authority to decide whether or not to apply for any amendment to the 666 Patent or the 946 Patent. He states that he is not aware of any similar amendments to those proposed by ICOS in respect of the 666 Patent and the 946 Patent having been considered or applied for in respect of any equivalent patents in other jurisdictions. He said that had that occurred, he would have been aware of it and he would have consulted with the responsible attorney with respect to those matters.
59 Dr Stewart first became aware of possible amendments to the 666 Patent and the 946 Patent during a discussion with Ms Palmberg in about August 2016. He understood from his discussion with Ms Palmberg, that it was Wrays which first proposed the idea of applying to amend the two patents. He had not previously given the matter any consideration. He received an email from Ms Palmberg on 20 September 2016. He states that at that time he considered that ICOS could successfully defend a challenge to the 946 Patent on the basis of utility without there being any amendment to the patent. He did not have any comments to make in relation to the proposed amendments to the 666 Patent.
60 Dr Stewart was aware of the NOC decision. He was aware of the nature of the proceeding and he was aware that regardless of the outcome of the NOC proceeding, a patent will remain valid and enforceable unless and until it is successfully challenged in revocation proceedings in court at a later date. It did not occur to him to amend the Canadian equivalent to the 946 Patent or any other patent that was equivalent to it. Dr Stewart considered the proposed amendments on 21 September 2016 and had a telephone conference with Wrays and Ms Palmberg on 22 September 2016. Dr Stewart explained the rationale for the amendments. It is convenient to set out his explanation in full:
25. Based upon my telephone conversation with Mr Cox, my understanding of the rationale for the proposed amendments to the 666 Patent was that although Wrays thought that the existing claims of the 666 Patent would survive Apotex's challenge to those claims being obvious, the proposed amendments may strengthen ICOS's defence to Apotex's obviousness claim. In particular, I understood that Wrays thought that in light of the findings in the UK decision in Actavis v ICOS (Actavis Group PTC ehf v ICOS Corporation [2015] EWHC 1955 (Pat)) concerning the inventiveness of the 5mg dose of tadalafil, ICOS' defence to Apotex's obviousness attack could be strengthened by adding narrower dependent claims that included integers relating to specific doses or dose ranges of tadalafil. I oversaw and attended the trial in the UK and read the Actavis v ICOS decision shortly after it was handed down.
26. Based upon my telephone conversation with Mr Cox, my understanding of the rationale for the proposed amendments to the 946 Patent was that the amendments would avoid the need for Apotex's utility challenge, or at least a substantial part of that challenge, to be heard and determined and thereby would save Lilly time and resources in having to answer that case. I also recall Mr Cox mentioning that there may be some uncertainty under Australian law as to whether or not all promises in a specification had to be met by the claimed invention. I recall expressing my view that ICOS could successfully defend a utility challenge in respect of the co-administration of tadalafil with organic nitrates by relying upon clinical data and expert evidence to be adduced from clinicians. Nevertheless, while I believed (and still believe) that the statements sought to be deleted from the 946 Patent could be supported by clinical evidence, once I understood Wrays' reasons for proposing the amendments to the 946 Patent, I was content for ICOS to pursue amendments to that patent in the form proposed by Wrays.
61 Mr Wood has been employed by Lilly as a patent attorney since 2003. He has qualifications in science and law, and he was registered as a patent attorney in 2003. Since about May 2006, Mr Wood has been the Lilly patent attorney with responsibility for the portfolio of patents relating to tadalafil. Mr Wood states that his role is to support Dr Stewart who has general oversight of patent litigation relating to the tadalafil portfolio in the United States and various other parts of the world.
62 Mr Wood first became aware of the possibility that the 666 Patent and the 946 Patent might be amended after receiving an email from Ms Palmberg on 20 September 2016. Mr Wood said that he was not aware of any amendments of the nature proposed with respect to the 666 Patent being proposed or considered in relation to any patents which are equivalent to that patent in the United States or in any other jurisdictions around the world. His position is such that he would have been informed if such amendments had been proposed or considered. He makes the same observations with respect to the proposed amendments to the 946 Patent.
63 Dr Mitchell joined the Lilly ICOS team working on the development of tadalafil in July 1998. ICOS had applied to the US Food and Drug Administration (FDA) for the Investigational New Drug (IND) designation for tadalafil before he joined the team. The IND was transferred from ICOS to Lilly ICOS at some point in 1999.
64 Dr Mitchell said that he was responsible for overseeing the clinical pharmacology studies required to support the registration of tadalafil. One such category of studies examined the interaction of tadalafil with nitrates. He was responsible for all the nitrate studies other than the first one which was designated "LVAB". All the other nitrate studies, namely LVBY, LVCM, LVCP and LVDN were performed under Dr Mitchell's supervision, and the study protocols were devised by him, either alone or in collaboration with others.
65 Dr Mitchell's view has been and still is that, based on the nitrate studies, the contraindication with nitrates for tadalafil is not warranted. His view, which is based on the results of the nitrate studies and data generated since, is that tadalafil can safely be used by most patients taking nitrate therapy and that it is generally safe for patients to be prescribed tadalafil while on nitrate therapy. Furthermore, he is aware of clinicians who safely prescribe tadalafil and nitrates together.
66 Finally, Apotex relied on correspondence that passed between the delegate of the Commissioner of Patents and Wrays in 2003 with respect to the 946 Patent. The delegate raised objections on the basis of a lack of novelty and a lack of an inventive step, and in response, Wrays made certain statements about the advantages of the invention in terms of its ability to eliminate or reduce side effects. Although there is little express reference to what is said to be the advantage in terms of the co-administration of tadalafil and organic nitrates, Apotex submits that in the context of what is said in the specification, the following statements by Wrays in the correspondence would be understood as referring to that advantage:
(1) "the presently claimed invention (a) effectively treats sexual dysfunction using a low dose of a particular PDE5 inhibitor, (b) eliminates or reduces various adverse side effects associated with current PDE5 inhibitor therapy used to treat sexual dysfunction (eg VIAGRA®) and (c) increases the population treatable for sexual dysfunction using a PDE5 inhibitor";
(2) "Clinical studies have shown that the presently claimed unit dosage composition is an effective product having a reduced tendency to cause flushing or visual abnormalities in susceptible individuals";
(3) "The present invention therefore, is an improvement over the main commercial PDE5 inhibitor treatment for sexual dysfunction, i.e., VIAGRA®";
(4) A person skilled in the art would not have been motivated from '675 and '978 to provide a unit dose composition as recited in the present claims with any expectation that the unit dosage composition would provide such unexpected results in the treatment of sexual dysfunction...The present invention, therefore, not only is novel and inventive over '675 and '978, but also satisfies unmet needs in the art";
(5) "… we note that neither specification contains any further reference to the advantages of dosage forms in the 0.1-20 mg range, nor do they provide any examples of dosage forms within this range, and we respectfully submit that the present invention constitutes a selection invention within the criteria listed in I.G. Farbenindustrie AG's Patents (1930) RPC 289"; and
(6) "… the selection of the compound and dosage range is based on 'detailed experiments and clinical trials' and it is at least implicit that the selected range represents a lower threshold at the compound is dosage form [sic] of treating the relevant disease states, and an upper threshold at which, whilst the compound is obviously capable of treating the desired disease states, the undesired side effects can no longer be considered clinically insignificant. Thus it can be said that the present invention satisfies the second and third criteria set down in the I.G. Farbenindustrie case in that the whole of the selected members possess the advantages in question, and that the advantages in questions are peculiar to the selected group."