FEDERAL COURT OF AUSTRALIA ViiV Healthcare Company v Gilead Sciences Pty Limited [2020] FCA 594 File number: VID 1332 of 2019 Judge: BEACH J Date of judgment: 4 May 2020 Catchwords: PRACTICE AND PROCEDURE – patents – anti-viral pharmaceutical compound to treat HIV – polycyclic carbamoylpyridone derivatives – integrase inhibitory activity – infringement of patent – structure of alleged infringing product – Biktarvy containing bictegravir as a sodium salt – position statement on infringement – integers of claims – bicyclic ring structures – disclosure of infringement case – application dismissed Case cited: VIIV Healthcare Company v Gilead Sciences Canada Inc 2020 FC 486 (unreported, Ottawa, Ontario, 6 April 2020) Date of hearing: 1 May 2020 Registry: Victoria Division: General Division National Practice Area: Intellectual Property Sub-area: Patents and associated Statutes Category: Catchwords Number of paragraphs: 47 Counsel for the Applicants: Mr D Shavin QC with Mr B Kremer Solicitor for the Applicants: Phillips Ormonde Fitzpatrick Lawyers Counsel for the Respondent: Mr C Dimitriadis SC with Mr L Merrick Solicitor for the Respondent: Herbert Smith Freehills ORDERS VID 1332 of 2019 BETWEEN: VIIV HEALTHCARE COMPANY First Applicant SHIONOGI & CO. LTD Second Applicant AND: GILEAD SCIENCES PTY LIMITED (ACN 072 611 708) Respondent JUDGE: BEACH J DATE OF ORDER: 4 MAY 2020 THE COURT ORDERS THAT: 1. The respondent's interlocutory application be refused. 2. The respondent pay the applicants' costs of and incidental to that application. Note: Entry of orders is dealt with in Rule 39.32 of the Federal Court Rules 2011. REASONS FOR JUDGMENT BEACH J: 1 The patent in suit (Australian patent no. 2006239177) concerns polycyclic carbamoylpyridone derivatives having HIV integrase inhibitory activity. The invention relates to compounds possessing such an antiviral activity and compositions containing such an anti-HIV agent. 2 HIV is a retrovirus which causes AIDS. It is an RNA virus, rather than a DNA virus; so too of course is SARS-CoV-2 which causes COVID-19 and is presently the subject of some attention. Now an enzyme being a retroviral integrase is produced by HIV. The function of the integrase is to insert the viral genome of HIV into the chromosomal DNA of a human cell through the formation of covalent bonds. Let me explain the process. The single-stranded viral RNA is reverse transcribed into double-stranded viral DNA. This occurs once the viral RNA has entered the host human cell and after the RNA has been liberated from the viral capsid that has entered the cell through endocytosis. The double-stranded viral DNA is then transported to and enters the host cell's nucleus. Such viral DNA is then integrated into the host cell's chromosomal DNA with that process facilitated by the retroviral integrase. The functionality of the retroviral integrase is to catalyse two reactions. First, two or three nucleotides are removed from the 3' ends of the viral DNA. Second, the processed 3' ends are then covalently ligated to the host cell's chromosomal DNA. The compounds and compositions of the patent are designed to inhibit such integrase activity so achieving the desired antiviral activity. In short, the integration is stymied. The zombie macro-molecule is not activated. 3 The applicants (collectively, ViiV) have brought an infringement suit against the respondent (Gilead) concerning Gilead's product marketed as Biktarvy. The marketing and sale of Biktarvy, a pharmaceutical composition containing as one of its active ingredients bictegravir as a sodium salt, is said to infringe claims 1 to 10, 28, 29, 43, 44 and 47 of the patent. Now an issue has arisen between the parties concerning the adequacy of ViiV's amended position statement on infringement which on 19 March 2020 I ordered to be filed. But before addressing that issue I need to say something more about the patent. 4 The patent is some 277 pages in length with some further inserted pages (pp 2a to 2h). There are 53 claims, but for the present it is only necessary to set out extracts from claims 1, 5 and 6. 5 The first part of claim 1 is in the following terms: 1. A compound of the formula: wherein, A ring is optionally substituted heterocycle; R14 and RX are independently hydrogen, optionally substituted C1-C10 alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted C3-C8 cycloalkyl C1-C10 alkyl, optionally substituted C2-C8 alkenyl, optionally substituted C1-C10 alkoxy, optionally substituted C2-C8 alkenyloxy, optionally substituted aryl, optionally substituted aryl C1-C10 alkyl… … a broken line represents the presence or absence of a bond, provided that when the broken line represents the presence of a bond, RX is not present; R1 is hydrogen or C1-C10 alkyl; X is a single bond, a heteroatom group selected from O, S, SO, SO2 and NH, or C1-C6 alkylene or C2-C6 alkenylene each may be intervened by the heteroatom group; R2 is optionally substituted aryl; R3 is hydrogen, halogen, hydroxy, optionally substituted C1-C10 alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted C2-C8 alkenyl, optionally substituted C1-C10 alkoxy, optionally substituted C2-C8 alkenyloxy, optionally substituted aryl, optionally substituted aryloxy, optionally substituted heterocyclic group, optionally substituted heterocycleoxy or optionally substituted amino); or a pharmaceutically acceptable salt, or solvate thereof; and wherein: (a) a group which is optionally substituted, other than optionally substituted amino, optionally substituted carbamoyl or optionally substituted phosphoric acid, is a group which is unsubstituted or substituted at any position by 1 to 4 substituents B, which are the same or different, B being selected from hydroxy, carboxy, halogen, halo C1-C10 alkyl, halo C1-C10 alkoxy, C1-C10 alkyl, C2-C8 alkenyl, ethynyl, C3-C8 cycloalkyl, cycloalkenyl, C1-C10 alkoxy C2-C8 alkenyloxy, C1-C10 alkoxycarbonyl, nitro, nitroso, optionally substituted amino, acylamino, aralkylamino, hydroxyamino, azido, aryl, aralkyl, cyano, isocyano, isocyanate, thiocyanate, isothiocyanate, mercapt, alkylthio, alkylsulfonyl, optionally substituted alkylsulfonylamino, optionally substituted carbamoyl, sulfamoyl, acyl, formyloxy, haloformyl, oxal, thioformyl, thiocarboxy, dithiocarboxy, thiocarbamoyl, sulfino, sulfo, sulfoamino, hydrazino, azido, ureido, amizino, quanidino, phthalimide, oxo, phosphoric acid residue, C1-C10 alkyl which is substituted with a phosphoric acid residue and may be intervened with a heteroatom group(s), aryl substituted with a phosphoric acid residue, aralkyl substituted with a phosphoric acid residue, hydroxyl C1-C10 alkyl, carboxy, halogen, halo C1-C10 alkyl, halo C1-C10 alkoxy, C1-C10 alkyl, C1-C10 alkoxy, optionally substituted amino, oxo and phosphoric acid residue; … [I do not need to set out (b) and (c)] 6 Claim 5 is in the following terms: 5. A compound according to Claim 1, pharmaceutically acceptable salt, or solvate thereof, wherein A ring is an optionally substituted and optionally condensed 5- to 7- membered heterocycle containing 1 to 2 hetero atom(s). 7 Further, claim 6, in part, is in the following terms: 6. A compound of the formula: wherein, A ring is an optionally substituted and optionally condensed 5- to 7- membered heterocycle containing 1 to 2 hetero atom(s); … [No further details need be set out by me] 8 Now before proceeding further, it is necessary to say something about rings given that an integer of claim 1 is expressed as an "A ring is [an] optionally substituted heterocycle" and an integer of claim 6 is an "A ring [which] is an optionally substituted and optionally condensed 5- to 7- membered heterocycle containing 1 to 2 hetero atom(s)". For convenience and for illustrative purposes only, I have drawn on what was said by Manson J in the Federal Court of Canada in VIIV Healthcare Company v Gilead Sciences Canada Inc 2020 FC 486 (unreported, Ottawa, Ontario, 6 April 2020) at [81] to [84] where he set out a number of straight-forward propositions concerning general structural features of heterocycles that I did not understand to be presently contentious. 9 First, a heterocycle is a cyclic structure (ring) that includes one or more non-carbon atoms, also known as heteroatoms. Heterocycles can be of any ring size, and can vary as to the number, type and position of heteroatoms. 10 Second, rings can be joined together to form bicyclic or polycyclic ring structures. Relevantly to the present case, there are three realistic ways in which rings can be joined. The structures are spiro, fused, and bridged shown as follows: 11 So, in the spiro structure two rings share a single atom. In the fused structure, two rings share two adjacent atoms. In the bridged structure, two rings share two non-adjacent atoms. 12 Let me now turn to ViiV's amended position statement on infringement. 13 The Federal Court's practice note concerning intellectual property litigation provides that a position statement on infringement should concisely state the facts and matters relied upon in support of an allegation of infringement, including by reference to the particular integers of any claim said to have been infringed (at [6.12]). 14 But before addressing the adequacy of ViiV's amended position statement, some general observations on position statements on infringement should be made, although my comments are not intended to be exhaustive. 15 First, whether dealing with an allegedly infringing product, process or method there needs to be a clear identification of the precise features thereof which are said to correspond with one or more integers of the asserted claim(s) of the patent in suit. 16 Whether pharmaceutical compounds, gadgets or some other subject matter, this can usually be advantageously portrayed by the use of diagrams or photographs, where available or suitable. Indeed, three-dimensional structures can readily be portrayed in two-dimensions. So, for example, chemists use Haworth projections and more generally drawing conventions to represent the 3D stereochemistry of molecules; and Markush structures can also be expressed in a Haworth projection. Such diagrams or pictorial representations of the alleged infringing subject matter can advantageously identify, by appropriate markings, the matching integer(s) of the asserted claim(s). 17 The short point is that diagrams or other pictorial representations should be used where possible. 18 Second, it must be clear from the position statement, whether expressed or necessarily implied, what is the construction of the integer(s) and the asserted claim(s) being advanced by the applicant which is the foundational assumption upon which the said matching underpinning the alleged infringement proposition is being made. 19 But this does not mean that the applicant has to justify any such construction including explaining any reasons for advancing it by reference to the complete specification. And nor does the applicant need to anticipate any contrary construction and rebut it in advance. Of course though, the applicant may wish to put a case on alternative constructions for the purpose of saying that whichever one applies, the alleged infringer loses. But if it seeks to do this, this should be made clear. 20 The point is that the position statement needs to be clear on the foundational construction being used by the applicant concerning the relevant integer(s) and the asserted claim(s). 21 The respondent's position statement in response should mirror the applicant's format to the extent possible. 22 First, if the allegedly infringing product, process or method has been incorrectly described by the applicant, this should be pointed out and it should be correctly and fully described by the respondent. 23 Second, the respondent should explain where it takes issue with the applicant's identification of features which are said to correspond with one or more integers of the asserted claim(s). 24 If the identification is erroneous because the product, process or method has been incorrectly described, the respondent should say so. 25 If the identification is erroneous because the respondent is advancing a different construction of the relevant integer(s) or claim(s) to that advanced by the applicant, this should be stated with the different construction identified. 26 If the identification is erroneous for some other reason, this should be stated and summarised. 27 Finally, I need say nothing concerning what a position statement should say on broader acts of sale, disposition, promoting, importing or authorising others to like effect, which are more conveniently dealt with in any event as particulars of infringement delivered and updated at the appropriate time. 28 Now ViiV says that Gilead has infringed each of claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 28, 29, 43, 44 and 47 of the patent by its dealings in the pharmaceutical composition known as Biktarvy. And it has said the following in its amended position statement on infringement. 29 Biktarvy is a pharmaceutical composition indicated for the treatment or prophylaxis of an HIV infection in humans being a fixed-dose combination containing the following active ingredients: (a) bictegravir as a sodium salt, an integrase strand transfer inhibitor having a molecular formula of C21H17F3N3NaO5 and the following structural formula: (b) emtricitabine, a nucleoside reverse transcriptase inhibitor; and (c) tenofovir alafenamide as fumarate, a reverse transcriptase inhibitor. 30 ViiV says that bictegravir is a compound falling within the scope of claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 43 and 44 and the Biktarvy product is a pharmaceutical composition falling within the scope of claims 28, 29 and 47. And it goes on to give the following detail. 31 On ViiV's case, bictegravir is a compound of the formula defined in claim 1 of the patent as set out below by reference to the integers defined by the claim: (a) The A ring is a heterocycle. It can be identified as a bridged bicyclic heterocycle having a 7 membered ring with two hetero atoms being nitrogen and oxygen, and a C1 (methylene) bridge in the position shown. Alternatively, it can be identified as a 6 membered ring with two hetero atoms being nitrogen and oxygen, and a C2 (ethylene) bridge in the position shown. (b) R14 is hydrogen. (c) Rx is hydrogen. (d) R1 is hydrogen. (e) X is C1 alkylene. (f) R2 is a substituted aryl, being phenyl substituted with three fluorine atoms. (g) R3 is hydrogen. (h) Bictegravir, as a sodium salt, is a pharmaceutically acceptable salt. 32 It is not necessary for present purposes to elaborate on what ViiV says concerning the infringement of claims 2, 3 and 4. 33 ViiV says that bictegravir is a compound according to claim 5 wherein the A ring is a heterocycle as set out in [31(a)] above. The bridged bicyclic structure can be identified as a condensed heterocycle containing two hetero atoms being nitrogen and oxygen, and it is in a sodium salt form, which is a pharmaceutically acceptable salt. 34 ViiV says that bictegravir is a compound of the formula defined in claim 6 as set out below by reference to the integers defined by the claim: (a) The A ring is a heterocycle as set out in [31(a)] above. The bridged bicyclic structure can be identified as a condensed heterocycle containing two hetero atoms being nitrogen and oxygen. (b) R14 is hydrogen. (c) Rx is hydrogen. (d) R3 is hydrogen. (e) R1 is hydrogen. (f) R is a halogen (fluorine) and m is the integer 3. (g) Bictegravir, in sodium salt form, is a pharmaceutically acceptable salt. 35 For present purposes it is not necessary to elaborate on what ViiV says concerning the infringement of the other claims. 36 There are two complaints raised by Gilead as to the adequacy of the amended position statement. 37 First, Gilead said that it was unclear what meaning ViiV was giving to the expression "A ring is [an] optionally substituted heterocycle" in claim 1. But it seems to me clear enough from the amended position statement that it was giving such a meaning as to include a bridged bicyclic heterocycle, whatever other type rings might be included, such as spirocyclic or fused bicyclic. It is saying that bictegravir is a ring, it is a heterocycle and as attached fits the integer. ViiV is not required to define the outer parameters of the integer but only to make clear what construction it is using to found the allegation of infringement bringing Gilead's product within the claim. 38 Now Gilead referred to other parts of the specification to suggest that when read in context, the said integer of claim 1 does not include a bridged bicyclic heterocycle. So, for example, it pointed to other passages of the specification to suggest that only spiro and fused rings were contemplated. Contrastingly, ViiV pointed to other passages to suggest otherwise. But all of these justifications and counter-justifications for the competing positions are matters for me to consider at trial in construing the specification as seen through the lens of a person skilled in the art. They are not matters for the present. 39 Gilead also queried whether ViiV's construction of the integer took into account or was to be informed by integer (a) being "a group which is optionally substituted…". In my view an interesting question but one that ViiV did not need to presently answer, although it attempted to do so in any event. It said that it was not so informed because the relevant ring was not "a group". I think one has to be careful in dealing with the concepts of "ring", "group" and "functional group". The first may be included within the other two depending upon function, position and structure. At all events I do not need to linger on this point for the moment given that ViiV's base proposition is clear. 40 Further, it will be up to Gilead to say what it likes in its position statement. No doubt it will deny infringement by accepting that bictegravir is a bridged bicyclic heterocycle, but rather asserting that the integer when read in context only includes spirocyclic or fused bicyclic structures. And no doubt, for example, it may say that paragraph (a) of claim 1 being "a group which is optionally substituted" and the groups listed limit the meaning of "A ring is [an] optionally substituted heterocycle" in the integer under discussion. Now if it wants to justify such positions by reference to other parts of the specification it is free to do so, but it is not required to do so in its position statement. 41 There is one further matter on this aspect. Gilead says that ViiV's present position is inconsistent with ViiV's position in the Canadian litigation and Manson J's findings (see at [140] and [174] to [176]). But I am required to construe a different patent utilising, to the extent that I find useful, the expert evidence adduced before me. Whether Gilead can leverage any defence or abuse of process point off Manson J's analysis will have to await another day. 42 Second, Gilead raised an issue concerning claims 5 and 6 and the reference to "condensed". Claim 5 refers to a compound according to claim 1 where the "A ring is an optionally substituted and optionally condensed 5- to 7- membered heterocycle containing 1 to 2 hetero atoms". Recall that claim 1 in the integer previously discussed does not use the expression "optionally condensed", does not stipulate the number of members of the ring, and does not stipulate the number of hetero atoms. Claim 6 stipulates a similar integer as claim 5 although it is an independent claim given that the principal integer refers to a compound of a different formula to claim 1. 43 Now Gilead's essential point is that ViiV has not said what construction it is using for "optionally condensed". Further and for effect, Gilead pointed out that Manson J had construed "condensed" to mean "fused", such that the relevant two rings had to share adjacent atoms and the bond(s) between them, thereby backing out from the potential possibilities covered by claims 5 and 6 a bridged bicyclic structure as being "condensed" because, as I have said, in a bridged structure the rings share only two non-adjacent atoms. Again this is a jury point. Manson J was construing the patent before him on the evidence led before him in accordance with Canadian law. But my task differs in all three aspects. 44 In my view, the amended position statement makes it clear that it is being asserted that the relevant ring of bictegravir is a heterocycle containing seven members with two hetero atoms, nitrogen and oxygen; alternatively it can be a six membered ring. And as the diagrams and descriptions indicate, it is being asserted that the bridged bicyclic structure is "optionally condensed". As to the phrase "optionally substituted", ViiV said that it was at this point no part of its infringement case. 45 So ViiV's assertion is that as shown on the diagrams, by reason of the ring being a bridged bicyclic structure, it is "condensed". Now Gilead pointed to p 49 of the specification to show that "condensed" should not be construed to include bridged, but only fused. But p 49 appears to refer to a preferred embodiment which could not of itself control the construction of the integer. Further, as ViiV pointed out, other passages such as pp 2h and 54 would suggest a broader meaning of "condensed" rather than just fused. 46 Whatever be the competing arguments, they are not matters for the present. It seems clear that the amended position statement is asserting that a bridged bicyclic structure is "optionally condensed" within the meaning of the integer(s), whatever else "condensed" might mean. Moreover, it is not necessary for ViiV at this point to chart its outer bounds such as to include fused or even spiro. 47 In summary, ViiV's amended position statement adequately performs the function required. Accordingly, Gilead's application must be dismissed with costs. I certify that the preceding forty-seven (47) numbered paragraphs are a true copy of the Reasons for Judgment herein of the Honourable Justice Beach. Associate: Dated: 4 May 2020