Samsung Bioepis AU Pty Ltd v Janssen Biotech, Inc

[2025] APO 32

IP AUSTRALIA

AUSTRALIAN PATENT OFFICE

Samsung Bioepis AU Pty Ltd v Janssen Biotech, Inc. [2025] APO 32

Patent Application:                2019346134

Title:Safe and effective method of treating ulcerative colitis with anti-IL12/IL23 antibody

Patent Applicant:                   Janssen Biotech, Inc.

Opponent:  Samsung Bioepis AU Pty Ltd

Delegate:  Dr A. Lim

Decision Date:  3 October 2025

Hearing Date:  18 December 2024 in Sydney

Further submissions filed 7 February 2025 and 21 February 2025

Catchwords:  PATENTS – section 59 – opposition to the grant of a patent – lack of novelty in light of documents established – whether disclosure of the results of the Phase III clinical trials is necessary for anticipation – the concept of parametritis considered – lack of inventive step in light of cited documents considered together with common general knowledge established – lack of support not established – opposition succeeds – costs awarded against applicant – opportunity to amend

Representation:  Counsel for the applicant:  Julian Cooke SC, Joseph Elks

Patent attorney for the applicant:  Davies Collison Cave

Counsel for the opponent:  Christian Dimitriadis SC,

Clare Cunliffe

Solicitor for the opponent:  Maddocks

IP AUSTRALIA

AUSTRALIAN PATENT OFFICE

Patent Application:                2019346134

Title:Safe and effective method of treating ulcerative colitis with anti-IL12/IL23 antibody

Patent Applicant:                   Janssen Biotech, Inc.

Date of Decision:                   3 October 2025

DECISION

The opposition is successful on the grounds of novelty and inventive step.  All the claims of the opposed application lack novelty in view of the cited prior art.  All the claims of the opposed application lack inventive step in light of cited prior art considered together with CGK.

The opponent has not established that any of the claims lack support from subject matter disclosed in the opposed application.

Janssen Biotech, Inc. is given two months from the date of this decision to propose amendments to overcome the deficiencies in the claims.

Costs according to Schedule 8 are awarded against Janssen Biotech, Inc..

REASONS FOR DECISION

Background

1. Patent application 2019346134 (the opposed application) was filed on 24 September 2019 under the provisions of the Patent Cooperation Treaty.  The opposed application claims priority from three US provisional applications and the earliest filing date of these applications is 24 September 2018.[1]

   [1] The three US provisional applications from which the opposed application, 2019346134, claims priority are US 62/735,501 having a filing date of 24 September 2018, US 62/769,818 having a filing date of 20 November 2018, and US 62/895,774 having a filing date of 04 September 2019.

2. The opposed application was examined and advertised accepted by the Commissioner on 12 January 2023.  Samsung Bioepis AU Pty Ltd (the opponent) filed a notice of opposition on 12 April 2023 and filed a statement of grounds and particulars (SGP) on 12 July 2023.  The opponent requested amendments to the SGP on 12 October 2023, the applicant was given an opportunity to provide comments but chose not to do so, and the requested SGP amendments were allowed.

3. Evidence in support (EIS) was filed by the opponent on 12 October 2023.  Janssen Biotech, Inc. (the applicant) filed evidence in answer (EIA) on 15 January 2024, and a request to make voluntary amendments to the claims of the opposed application on 29 January 2024.  Leave to amend the specification was granted and details of the request to amend were subsequently advertised on 28 March 2024 for opposition purposes.  No opposition was filed regarding the applicant’s amendments of 29 January 2024.  The amendments were allowed, and allowance of the amendments was published on 20 June 2024.  Consequently, the applicant’s amendments of 29 January 2024 form part of the specification and the opposition proceeds in respect of the amended claims.

4. Evidence in reply (EIR) was filed by the opponent on 18 March 2024.

5. A hearing was scheduled for Wednesday 18 December 2024 in Sydney.  In accordance with the Commissioner’s direction in the hearing notice, the opponent and applicant both filed a written summary of submissions before the hearing on the 04 December 2024 (the OS) and 11 December 2024 (the AS), respectively.  On 16 December 2024, the opponent filed further written submissions in reply to the applicant’s written submissions (the ORS).  On 17 December 2024, the applicant wrote a letter to the Commissioner alleging that the opponent’s written reply submissions “would result in significant prejudice to the Applicant if they were to be considered by the Hearing Officer without the Applicant being afforded an adequate opportunity to consider the submissions and respond in writing” (emphasis in original).  The applicant requested that the Commissioner urgently issue a direction to defer the hearing and provide the applicant with at least five business days to respond to the ORS.

6. A delegate of the Commissioner responded to the applicant’s letter on the same day and indicated that it was not necessary to vacate the hearing scheduled for 18 December 2024 to afford the applicant procedural fairness.  The delegate noted that to the extent that the applicant considered it was unable to properly respond to the ORS, the Commissioner can provide the Applicant with a period after the hearing to file written submissions that address the ORS.  The delegate suggested that the applicant raise the issue of post-hearing submissions at the hearing and indicate how much time it considers appropriate to file further submissions.  The delegate also noted that this would ensure procedural fairness while allowing the hearing to proceed.

7. At the hearing the applicant requested until 07 February 2025 to file written submissions to address the ORS.  In all the circumstances, including the time of year being close to the Christmas and New Year holidays, I considered this period reasonable.  I also agreed to the opponent’s request for an opportunity to respond to the applicant’s post-hearing submissions and gave the opponent two weeks after the filing of the applicant’s post-hearing submissions to respond.  I confirmed the provision of post-hearing submissions in a letter dated 19 December 2024 and noted that any post-hearing submissions had to be strictly limited to addressing matters in the ORS.

8. On 07 February 2025, the applicant filed post-hearing reply submissions (the APHS) to the ORS.  The opponent filed responsive submissions to the APHS on 21 February 2025 (the OPHS).  I am satisfied that the APHS have been limited to the ORS and the OPHS have been limited to the APHS.

   The opposition

9. The grounds of opposition stated in the SGP are:

   ·lack of novelty,

   ·lack of inventive step, and

   ·lack of support.

10. The evidence is summarised in the able below.

Evidence	Declarant	Exhibits	Date	Reference
In Support	Stephen James Rohl	SJR-1 to SJR-6	12 October 2023	Rohl #1
	Veysel Kayser	VK-1 to VK-4	12 October 2023	Kayser
	Paul Pavli	PP-1 to PP-11	12 October 2023	Pavli #1
In Answer	Matthew Aaron Ciorba	MAC-1 to MAC-8	14 January 2024	Ciorba
	John Kornak	JK-1 to JK-5	13 January 2024	Kornak
In Reply	Stephen James Rohl	SJR-7 to SJR-19	18 March 2024	Rohl #2
	Paul Pavli	PP-12 to PP-13	18 March 2024	Pavli #2

1. Since the opposed application was filed on 24 September 2019 this application is governed by the Patents Act 1990 (the Act) as amended by the Intellectual Property Laws Amendment (Raising the Bar) Act 2012. This includes subsection 60(3A) of the Act which states:

   (3A) If the Commissioner is satisfied, on the balance of probabilities, that a ground of opposition to the grant of the standard patent exists, the Commissioner may refuse the application.

2. The standard of proof that applies to the present opposition is the balance of probabilities, and the opponent carries the onus of proof.

   The specification

3. The field of the invention relates to

   “methods of providing a clinically proven safe and clinically proven effective treatment of ulcerative colitis, particularly moderately to severely active ulcerative colitis in patients who have had an inadequate response to or are intolerant of a conventional or existing therapy by intravenous and/or subcutaneous administration of an anti-IL-12/IL-23p40 antibody.”[2]

   [2] The specification at page 1, lines 13-17.

4. The specification as amended up to this point in time has 30 claims.  Claims 1, 17, 29 and 30 are the independent claims.  The claim set is reproduced in Annex A of this decision.

   Principles of construction

5. Before commencing to construe the specification, I note what Middleton J said in Eli Lilly and Company Limited v Apotex Pty Ltd:

   “It is well settled that the Court should, from the outset, approach the task of patent construction with a generous measure of common sense.  The Court must place itself in the position of a person skilled in the relevant art, being the subject matter of the patent.  From this perspective, the patent is to be read as a whole, in the context of the specification and in light of the prevailing common general knowledge and state of the relevant art at the priority date.”[3]

   [3] [2013] FCA 214 at [139]; 100 IPR 451.

   The person skilled in the art (PSA)

6. It is well established that many of the issues in an opposition are answered by reference to the PSA:

   “He is the person to whom the patent is addressed and who must construe it.  He is the person whose knowledge will determine whether a patent is novel.  He is the person who will judge whether a patent is obvious.”[4]

   [4] Root Quality Pty Ltd v Root Control Technologies Pty Ltd [2000] FCA 980 at [70]; 177 ALR 231.

7. However, the PSA is an artificial construct that is used as a tool of analysis, and there is a danger in trying to identify them as an actual person or persons:

   “The notional person is not an avatar for expert witnesses whose testimony is accepted by the court.  It is a pale shadow of a real person – a tool of analysis which guides the court in determining, by reference to expert and other evidence, whether an invention as claimed does not involve an inventive step.”[5]

   [5] AstraZeneca AB v Apotex Pty Ltd [2015] HCA 30 at [23]; 89 ALJR 798.

8. An understanding of the PSA is based on evidence from persons with knowledge of the art as to the things that they know and do, and what they understand to be commonly known and done.  The qualifications of the expert witnesses, relevant to the present opposition, are summarised below.  The opponent relies on the evidence of Professor Paul Pavli, Associate Professor Veysel Kayser, and Mr Stephen James Rohl.  The applicant relies on the evidence of Professor Matthew Aaron Ciorba and Professor John Kornak.

9. Professor Pavli is a gastroenterologist with almost 40 years of experience.[6]  He has worked in the field of gastroenterology since 1984 and has lectured on the pathophysiology, treatment and management of IBD for over 25 years.[7]  Professor Pavli has undertaken research focusing on the clinical and basic scientific aspects of IBD, particularly on the causes of Crohn’s disease (CD) and ulcerative colitis (UC), the role of inflammatory cells in these diseases, and treatments for these diseases.[8]  Since 1999, Professor Pavli has been involved in a number of clinical trials including investigation of new therapeutic agents and existing therapeutic agents (approved for conditions other than CD and/or UC) in the treatment of CD and/or UC as part of multinational, multicentre research programs, frequently as a principal investigator.[9]  He has also acted as an independent evaluator of applications to register new medicines and new indications for the Therapeutic Goods Administration on several occasions between 2001 and 2004, and served on the Australian Drug Evaluation Committee between 2005 and 2022.[10]

   [6] Pavli # 1 at [1].

   [7] Pavli # 1 at [15], [26].

   [8] Pavli # 1 at [27].

   [9] Pavli # 1 at [29]-[30]; Annexure PP-3 to Pavli # 1.

   [10] Pavli # 1 at [46]-[47].

10. Associate Professor Kayser is a pharmaceutical scientist with almost 20 years’ experience, particularly in relation to development, formulation and stability of biologic medicines and vaccines.  He is an Associate Professor at the University of Sydney.[11]

    [11] Kayser at [1].

11. Mr Rohl is a solicitor for the opponent.  His declarations deal with the cited prior art and particular matters the opponent considered relevant to the CGK.

12. Professor Ciorba is a gastroenterologist, Professor of Medicine, and Director of IBDs Research at Washington University in St Louis, Missouri, in the United States.[12]  Professor Ciorba has been specialising in gastroenterology since 2004 and his clinical practice and research is primarily directed to advancing care for patients affected by CD, UC and colon cancer.[13]  His research includes defining pathways and mechanism of intestinal inflammation and the transition to colon cancer.[14]  Professor Ciorba has been a principal investigator in multiple clinical trials for CD and UC treatments.[15]  He has been a member of numerous scientific panels including the Colitis Foundation of America and the American Gastroenterological Association (AGA).[16]

    [12] Ciorba at [1], Part B; Annexure MAC-2 to Ciorba.

    [13] Ciorba at [1], [12].

    [14] Ciorba at [16].

    [15] Ciorba at [18].

    [16] Ciorba at [28].

13. Professor Kornak is a biostatistician at the University of California, San Francisco, in the United States.[17]  Professor Kornak gives evidence on the role of statistical analysis in clinical studies.

    [17] Kornak at [1].

14. The opponent submitted that the role of statistical analysis in clinical studies is entirely irrelevant to the questions of novelty, inventive step and support.[18]  In the present circumstances, I consider that the grounds of opposition can be addressed adequately by considering the disclosure in the (1) cited prior art, together where appropriate, with CGK, or (2) specification.  Therefore, for this opposition I am of the view that evidence on the role of statistical analysis in clinical studies is not necessary.

    [18] The OS at [12(b)].

15. The opponent also submitted that Professor Ciorba’s evidence (1) reflects matters peculiar to the USA, not the CGK worldwide, and (2) addresses the wrong standard as he often substitutes a test for prediction for a test of expectation.[19]

    [19] The OS at [12(a)]; the ORS at [6].

16. The applicant submitted that Professor Pavli’s evidence (1) is limited to the CGK in Australia only, and (2) regarding the hypothetical task he was given for the assessment of inventive step, is tainted by hindsight because of his involvement in the Phase III clinical trial for ustekinumab (known as the UNIFI clinical trial) and his off-label experience with ustekinumab.[20]

    [20] The AS at [18], [199]; Annexure PP-3 to Pavli # 1.

17. I consider that Professor Pavli and Professor Ciorba emphasised the practices in their own jurisdiction but were aware of the CGK worldwide.  I will consider the evidence of all declarants in the context of their experience and knowledge.  The weighing and evaluating of the evidence are part of the normal work of a delegate of the Commissioner.

    The background to the invention

18. The specification describes inflammatory bowel diseases (IBDs), which include ulcerative colitis (UC), as chronic relapsing disorders characterised by destructive inflammation and epithelial injury in the gastrointestinal (GI) tract.[21]

    [21] The specification at page 1, lines 20-22.

19. The etiology of UC is described as unknown but abnormal immune responses to contents in the gut, including intestinal microbes, are thought to drive disease in genetically predisposed individuals.[22]

    [22] The specification at page 1, lines 27-29.

20. The specification describes the involvement of the IL-12/IL-23 pathway in the pathogenesis of IBD to be well-established and that an important role for the IL-12/IL-23 pathway in intestinal inflammation has been elucidated in colitis.[23]

    [23] The specification at page 2, lines 6-8.

21. Biologic therapies that are currently approved for the treatment of UC are described to be either tumour necrosis factor (TNF) or integrin inhibitors.  However, out of all the approved treatments, only vedolizumab has demonstrated efficacy in subjects who have had an inadequate response or are intolerant to anti-TNFs.[24]  Furthermore, it has been observed that there are subjects receiving vedolizumab for the treatment of UC who show inadequate response and intolerance to their treatment.[25]

    [24] The specification at page 2, lines 24-27.  I understand vedolizumab to be an integrin inhibitor.

    [25] The specification at page 2, line 29 to page 3, line 1.

22. Biologic therapies that are currently approved for the treatment of UC are described to also demonstrate efficacy in CD.[26]  The specification explains that multiple lines of evidence suggest that inflammatory bowel disease (UC and CD) is mediated by T helper 1 (Th1) or T helper 17 (Th17) cells with strong contribution from the proinflammatory cytokines, IL-12 and IL-23.[27]

    [26] The specification at page 3, lines 3-4.

    [27] The specification at page 3, lines 5-7.

23. The specification describes ustekinumab (STELARA®) to be a fully human monoclonal antibody to human IL-12/23p40 that prevents IL-12 and IL-23 bioactivity by inhibiting their interaction with the cell surface IL-12Rß1 receptor protein.  Ustekinumab effectively neutralises IL-12 (Th1)- and IL-23 (Th17)-mediated cellular responses through this mechanism of action.[28]  Ustekinumab is described as having received marketing approval in countries in North America, Europe, South America and the Asia-Pacific region, for the treatment of adults with moderately to severely active CD, moderate to severe plaque psoriasis, or active psoriatic arthritis, as well as for paediatric subjects (12 to 17 years old) with moderate to severe plaque psoriasis.  The first approval for CD was received on 11 November 2016.[29]

    [28] The specification at page 3, lines 7-12.

    [29] The specification at page 3, lines 12-17.

24. The specification explains that the efficacy and safety of intravenous ustekinumab therapy in CD have been evaluated in clinical studies.[30]  Ustekinumab is reported to demonstrate clinically significant efficacy compared with placebo and was well tolerated with a favourable safety profile.[31]

    [30] The specification a page 3, lines 18-19.

    [31] The specification at page 3, lines 27-28.

    Aim of the invention

25. The specification explains that there is a need in the art for improved methods of treating UC, particularly moderate to severely active UC in subjects who had previously failed or were intolerant of a biologic therapy or other conventional therapy, or subjects who had demonstrated corticosteroid dependence.[32]

    [32] The specification at page 4, lines 1-4.

26. The summary of the invention is described in similar terms of the field of the invention outlined above, this being:

    “clinically proven safe and clinically proven effective methods and compositions for treatment of moderately to severely active ulcerative colitis (UC), particularly in subjects who have had an inadequate response to or are intolerant of a conventional or existing therapy, by administration of an anti-IL-12/IL-23p40 antibody to subjects, thereby addressing a clear unmet medical need in this subject population.”[33]

    [33] The specification at page 4, lines 9-13.

27. I infer that the aim of the invention is to provide an alternative method of treating UC, particularly in a subject who has had an inadequate response to, or is intolerant of, a conventional or existing therapy, by administration of an anti-IL-12/IL-23p40 antibody.

28. It is useful to note here that the specification uses the terms “anti-IL-12/IL-23p40 antibody”, “IL-12/23p40 antibody”, “anti-IL-12 antibody” and “anti-IL-23 antibody”, interchangeably to refer to a monoclonal antibody (mAb) or antigen binding fragment thereof, that binds to the 40 kDa (p40) subunit shared by cytokines interleukin-12 and interleukin 23 (IL-12/23p40).[34]  Ustekinumab is an embodiment of such a mAb.[35]

    [34] The specification at page 10, lines 19-22.

    [35] The specification at page 31, lines 16-18.

    The invention as described in the specification

1. The specification uses some terms to describe various parts of an antibody that are understood by the skilled person.  It is useful to provide an explanation of some of these terms here.  Professor Ciorba provides a drawing of a typical structure of an antibody adapted from Hansel et al 2010 Nature Reviews Drug Discovery 9, 325-338).[36]  I reproduce the drawing below.

   [36] Ciorba at [73].

2. Professor Ciorba explains that:

   “Broadly speaking, an antibody molecule is made up of four polypeptide chains; two heavy chains and two light chains (colored blue and orange respectively, in [the drawing above]).  The heavy chains are partially bound together in a ‘Y’ shape, and each heavy chain is linked to a light chain by disulphide bonds.

   Each arm of the Y-shaped antibody structure is formed by the association of a light chain with the amino-terminal half of a heavy chain, to form the Fragment Antigen Binding (Fab) region that contains the antigen-binding site.  The antigen binding site contains complementarity determining regions (CDRs), which are short stretches of amino acid sequences within the variable domains of the heavy chain and light chains (VH and VL, respectively), that come into contact with the antigen (i.e., a specific site on a target molecule).  Generally speaking, the amino acid sequence of the CDRs informs the binding specificity and affinity of the antibody molecule.  The stem of the Y-shaped antibody structure is the Fragment Crystallizable (Fc) region, formed by the constant regions of the heavy chains, and is responsible for antibody effector function, as the region interacts with Fc receptors and complement proteins.  The Fc region is typically not important for targeting and neutralising soluble antigens, including soluble inflammatory cytokines.  However, the Fc region can play a role in pharmacokinetics / bioavailability.”[37] (bold font in original)

   [37] Ciorba at [73]-[74].

3. The specification describes several aspects of the invention, and each aspect generally mirrors an independent claim in the claim set (as amended on 29 January 2024) of the present invention.  A first aspect is a method of treating moderately to severely active UC in a subject in need thereof, comprising:

   ·administering to the subject a pharmaceutical composition comprising an effective amount of anti-IL-12/IL-23p40 antibody,

   wherein

   ·after treating with the antibody, the subject is a responder to treatment by at least one measure of response to treatment selected from a group consisting of seven efficacy criteria which are defined.[38]

   [38] The specification at page 4, line 14 to page 4a, line 7.  I note that two of the seven efficacy criteria were subsequently deleted from independent claim 1 in the amendments of 29 January 2024.

4. The efficacy criteria are defined by reference to (a) various indices for measurement of disease activity including a Mayo Score, or a Mayo subscore, or (b) an Inflammatory Bowel Disease Questionnaire (IBDQ) score which is an assessment of disease-specific health-related quality of life.[39]

   [39] The specification at page 4, line 25 to page 4a, line 7, and page 77, line 14.

5. The Mayo score is described as an established, validated disease activity index for mild, moderate, and severe ulcerative colitis (UC) that is calculated as the sum of the four subscores of stool frequency, rectal bleeding, findings of endoscopy, and physicians’ global assessment (PGA), and its value ranges from 0-12.  A score of 3-5 indicates mildly active disease, a score of 6-10 indicates moderately active disease, and a score of 11-12 points indicates severe disease.[40]

   [40] The specification at page 13, lines 19-24.

6. The specification defines “clinical response” as a decrease from induction baseline in the Mayo score by ≥30% and ≥3 points, with either a decrease from baseline in the rectal bleeding subscore ≥1 or a rectal bleeding subscore of 0 or 1.[41]

   [41] The specification at page 14, lines 7-10.

7. A second aspect of the invention described is a method of treating moderately to severely active UC in a subject in need thereof, comprising:

   ·(a) intravenously administering to the subject an anti-IL-12/IL-23p40 antibody in a first pharmaceutical composition at a dosage of about 6.0 mg/kg body weight of the subject or 130 mg, 260 mg, 390 mg or 520 mg per administration at week 0 of the treatment,

   and

   ·(b) subcutaneously administering to the subject the anti-IL-12/IL-23p40 antibody in a second pharmaceutical composition at a dosage of 90 mg per administration at week 8 of the treatment,

   wherein

   ·the subject is a responder to treatment by at least one measure of response to treatment selected from a group consisting of seven efficacy criteria which are defined,

   and wherein

   ·the subject had previously failed or was intolerant of at least one therapy selected from a group consisting of five defined therapies (these being, an anti-TNF, vedolizumab, corticosteroids, azathioprine (AZA), and 6 mercaptopurine (6 MP)), or the subject had demonstrated corticosteroid dependence.[42]

   [42] The specification at page 4a, line 8 to page 4b, line 5.  I note that two of the seven efficacy criteria were subsequently deleted from independent claim 17 in the amendments of 29 January 2024.

8. A third aspect of the invention described is a method of treating moderately to severely active UC in a subject in need thereof, comprising:

   ·(a) intravenously administering to the subject an anti-IL-12/IL-23p40 antibody in a first pharmaceutical composition at a dosage of about 6.0 mg/kg body weight of the subject or 130 mg, 260 mg, 390 mg or 520 mg per administration at week 0 of the treatment,

   and

   ·(b) subcutaneously administering to the subject the anti-IL-12/IL-23p40 antibody in a second pharmaceutical composition at a dosage of 90 mg per administration at week 8 of the treatment,

   ·followed by a maintenance therapy, wherein the maintenance therapy comprises subcutaneously administering to the subject the anti-IL-12/IL-23p40 antibody at a dosage of 90 mg per administration, once every 8 weeks or once every 12 weeks, wherein the maintenance therapy is provided for 44 weeks

   and

   ·after treating with the antibody, the subject is a responder to treatment by at least one measure of response to treatment selected from a group consisting of seven efficacy criteria which are defined.[43]

   [43] The specification at page 4b, line 6 to page 4c, line 4.  I note that two of the seven efficacy criteria were subsequently deleted from independent claim 29 in the amendments of 29 January 2024.

9. The anti-IL-12/IL-23p40 antibody of the first, second and third aspects of the invention is described to comprise a heavy chain variable region and a light chain variable region,

   ·the heavy chain variable region comprising a complementarity determining region heavy chain 1 (CDRH1) amino acid sequence of SEQ ID No:1, a CDRH2 amino acid of SEQ ID No:2, and a CDRH3 amino acid of SEQ ID No:3;

   and

   ·the light chain variable region comprising a complementarity determining region light chain 1 (CDRL1) amino acid sequence of SEQ ID No:4, a CDRL2 amino acid of SEQ ID No:5, and a CDRL3 amino acid of SEQ ID No:6.[44]

   [44] The specification at page 4, lines 17-23, page 4a, lines 15-21, page 4b, lines 13-19.  The amino acids of SEQ ID No: 1 to SEQ ID No: 6 are described in the sequence listings of the opposed application.

10. A fourth aspect of the invention described is a method of treating moderately to severely active UC in a subject in need thereof, comprising:

    ·(a) intravenously administering to the subject an anti-IL-12/IL-23p40 antibody comprising a heavy chain variable region of amino acid of SEQ ID No: 7 and a light chain variable region of amino acid SEQ ID No: 8 in a first pharmaceutical composition at a dosage of about 6.0 mg/kg body weight of the subject or 130 mg, 260 mg, 390 mg or 520 mg per administration at week 0 of the treatment,

    and

    ·(b) subcutaneously administering to the subject the anti-IL-12/IL-23p40 antibody in a second pharmaceutical composition at a dosage of 90 mg per administration at week 8 of the treatment,

    ·followed by a maintenance therapy, wherein the maintenance therapy comprises subcutaneously administering to the subject the anti-IL-12/IL-23p40 antibody at a dosage of 90 mg per administration, once every 8 weeks or once every 12 weeks,

    and

    ·after treating with the antibody, the subject is a responder to treatment by at least one measure of response to treatment selected from a group consisting of seven efficacy criteria which are defined.[45]

    [45] The specification at page 4c, lines 5-26.  The amino acids of SEQ ID No: 7 and SEQ ID No: 8 are described in the sequence listings of the opposed application.  I note that two of the seven efficacy criteria were subsequently deleted from independent claim 30 in the amendments of 29 January 2024.

11. In some embodiments, the methods of the opposed application are described to comprise intravenously and/or subcutaneously administering to the subject a pharmaceutical composition comprising the anti-IL-12/IL-23p40 antibody ustekinumab, which comprises a heavy chain amino acid sequence of SEQ ID 10 and a light chain amino acid sequence of SEQ ID No:11.[46]

    [46] The specification at page 6, lines 3-7.  The amino acids of SEQ ID No: 10 and SEQ ID No: 11 are described in the sequence listings of the opposed application.

12. In some embodiments, the anti-IL-12/IL-23p40 antibody is in a pharmaceutical composition for intravenous administration comprising a solution comprising 10 mM L-histidine, 8.5% (w/v) sucrose, 0.04% (w/v) polysorbate 80, 0.4 mg/mL L-methionine, and 20 µg/mL EDTA disodium salt, dehydrate, at pH 6.0.[47]

    [47] The specification at page 7, lines 18-20.  As noted in the decision, specification uses the terms “anti-IL-12 antibody”, “anti-IL-23 antibody”, “anti-IL-12/IL-23p40 antibody” and “IL-12/23p40 antibody” interchangeably to refer to a monoclonal antibody (mAb) or antigen binding fragment thereof, that binds to the 40 kDa (p40) subunit shared by cytokines interleukin-12 and interleukin 23 (IL-12/23p40), see specification page 10, lines 19-22.

13. In other embodiments, the anti-IL-12/IL-23p40 antibody is in a pharmaceutical composition for subcutaneous administration comprising a solution comprising 6.7 mM L-histidine, 7.6% (w/v) sucrose, 0.004% (w/v) polysorbate 80, at pH6.0.[48]

    [48] The specification at page 7, lines 23-24.  As noted in the decision, specification uses the terms “anti-IL-12 antibody”, “anti-IL-23 antibody”, “anti-IL-12/IL-23p40 antibody” and “IL-12/23p40 antibody” interchangeably to refer to a monoclonal antibody (mAb) or antigen binding fragment thereof, that binds to the 40 kDa (p40) subunit shared by cytokines interleukin-12 and interleukin 23 (IL-12/23p40), see specification page 10, lines 19-22.

14. Examples 1 and 2 of the specification describe an induction study and a maintenance study, respectively, designed to assess the efficacy of ustekinumab in human subjects with moderately to severely active UC who demonstrated inadequate response to, or failure to tolerate, conventional (corticosteroids or 6-mercaptopurine (6-MP) or azathioprine (AZA)) or biologic therapy (TNF-antagonist and/or the integrin antagonist, vedolizumab).[49]  Example 1 refers to a “Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Safety and Efficacy of ustekinumab Induction and Maintenance Therapy in Subjects with Moderately to Severely Active Ulcerative Colitis”.[50]  Professor Pavli and Professor Ciorba recognise Examples 1 and 2 of the specification as the induction study and the maintenance study, respectively, within a Phase III clinical trial for ustekinumab known as the UNIFI clinical trial.[51]  The UNIFI clinical trial is described in a record that was published on the ClinicalTrials.gov website, and this publication has been raised as a prior art citation (CTR 236) in the present opposition.[52]  I will discuss CTR 236 in due course.

    [49] Example 1 begins on page 63 of the specification.  Example 2 begins on page 75 of the specification.

    [50] The specification at page 63, lines 12-14, page 64, lines 14-15.

    [51] Pavli #1 at [259]; Ciorba at [237].

    [52] Pavli #1 at [259].

    Example 1

15. In the induction study, subjects were randomised at week 0 to one of three treatment groups:

    a.Placebo

    b.“low-dose ustekinumab”, which received a single 130 mg intravenous (IV) dose of ustekinumab; or

    c.“high-dose ustekinumab”, which received a single weight-range based dose of approximately 6 mg/kg IV of ustekinumab, this being 260 mg for a body weight ≤55 kg, 390 mg for a body weight ˃ 55 kg but ≤85 kg, and 520 mg for body weight ˃85 kg.[53]

    [53] The specification at page 64, line 15-17, page 65, lines 1-8.

16. All subjects were evaluated for clinical remission and clinical response at week 8.[54]  Subjects who demonstrated no clinical response at week 8 received an additional IV or subcutaneous (SC) dose of ustekinumab.[55]  Subjects who demonstrated a clinical response at week 8 or week 16 (following the additional dose) were eligible to enter the maintenance study, which is described to evaluate maintenance therapy using SC ustekinumab.[56]

    [54] The specification at page 64, lines17-18.

    [55] The dosages are described in the specification at page 65, lines 10-14.  Subjects who were randomised to placebo at Week 0 received one weight-range based dose of approximately 6 mg/kg IV of ustekinumab +placebo SC, to maintain the blind, at Week 8.  Subjects who were randomised to ustekinumab at Week 0 received one dose of 90 mg SC of ustekinumab + placebo IV, to maintain the blind, at Week 8.

    [56] The specification at page 64, lines 18-29.

17. Efficacy evaluations were collected throughout the clinical trial and the efficacy criteria for the induction study included:[57]

    [57] The specification at page 66, line 24 to page 67, line 8.

    a.clinical remission (global definition): Mayo score ≤2points, with no individual subscore ˃1;

    b.clinical remission (US definition): absolute stool number ≤3, rectal bleeding subscore of 0, and Mayo endoscopy subscore of 0 or 1;

    c.clinical response: a decrease from induction baseline in the Mayo score by ≥30% and ≥3 points, with either a decrease from baseline in the rectal bleeding subscore ≥1 or a rectal bleeding subscore of 0 or 1;

    d.endoscopic healing (i.e., improvement in the endoscopic appearance of the mucosa): Mayo endoscopy subscore of 0 or 1

    e.histological healing: based on the Geboes score and is defined as 0 to ˂5% neutrophils in the epithelium and no crypt destruction, erosion, ulcerations, or granulations;

    f.mucosal healing: both endoscopic healing and histologic healing

18. The efficacy results for the induction study are described as follows:

    “Clinical Remission at Week 8- Global Definition
    At Week 8, significantly greater proportions of subjects in the ~6 mg/kg and 130 mg groups achieved clinical remission (15.5% and 15.6%, respectively) compared with subjects in the placebo group (5.3%; p<0.001 for both comparisons; Table 1).”[58]

    [58] The specification at page 69, lines 20-24.

    “Clinical Remission at Week 8- US Definition
    At Week 8, significantly greater proportions of subjects in the ~6 mg/kg and 130 mg groups achieved clinical remission (18.9% and 16.6%, respectively) compared with subjects in the placebo group (6.3%; p<0.001 for both comparisons; Table 2).”[59]

    [59] The specification at page 70, lines 3-6.

    “Clinical Response at Week 8

    At Week 8, significantly greater proportions of subjects in the ~6 mg/kg and 130 mg groups achieved clinical response (61.8% and 51.3%, respectively) compared with subjects in the placebo group (31.3%; p<0.001 for both comparisons; Table 4).”[60]

    [60] The specification at page 71, lines 4-6.

    “Endoscopic Healing at Week 8
    At Week 8, significantly greater proportions of subjects in the ~6 mg/kg and 130 mg groups achieved endoscopic healing (27.0% and 26.3%, respectively) compared with subjects in the placebo group (13.8%; p<0.001 for both comparisons; Table 3).”[61]

    [61] The specification at page 70, lines 11-14.

    “Histologic Healing at Week 8
    Histologic healing was defined as 0 to <5% neutrophils in epithelium and no crypt destruction, erosions, ulcerations, or granulations.  At Week 8, significantly greater proportions of subjects in the ~6 mg/kg and 130 mg groups achieved histologic healing (35.6% and 37.9%, respectively) compared with subjects in the placebo group (21.9%; p<0.001 for both comparisons).”[62]

    [62] The specification at page 72, lines 15-19.

19. The specification reports that median IBDQ scores were similar across all treatment groups at baseline, and

    “[a]t Week 8, the median improvements from baseline in the IBDQ scores were significantly greater in the ~6 mg/kg and 130 mg groups (31.0 and 31.5, respectively) compared with the placebo group (10.0; p<0.001 for both comparisons).”[63]

    [63] The specification at page 71, line 11 to page 72, line 2.  While the specification does not explain the reference point for “at baseline”, the opponent’s interpretation that this is Week 0 (see OS at [34]) seems reasonable in the context of the efficacy evaluation being made for changes to IBDQ scores.

20. The specification also describes other efficacy criteria and reports the results for these other criteria.[64]  Additionally, the results for the safety, pharmacokinetics and immunogenicity of administering ustekinumab intravenously are also reported.[65]

    [64] The specification at page 67, lines 9-22, page 72, lines 3 to page75, line 7.

    [65] The specification at page 67, line 24 to page 69, line 18.

    Example 2

21. Example 2 is a “[m]aintenance Study of ustekinumab in the treatment of ulcerative colitis in humans”[66].  The specification describes the “primary” population in the maintenance study as subjects who were in clinical response to IV Ustekinumab following the induction study, specifically:

    [66] The specification at page 75, lines 9-10.

    a)Subjects who received 130 mg or ~6 mg/kg IV ustekinumab at induction week 0 and were in clinical response at induction week 8; and

    b)Subjects who received placebo at induction week 0, were not in clinical response at induction week 8 but were in clinical response at induction week 16 after receiving ~6 mg/kg IV ustekinumab at induction week 8.[67]

    [67] The specification at page 75, lines 9-21.

22. The subjects were randomised at maintenance week 0 to receive ustekinumab 90 mg SC every 8 weeks (q8w), ustekinumab 90 mg SC every 12 weeks (q12w), or placebo SC.[68]

    [68] The specification at page 75, lines 22-23.

23. The specification describes the primary endpoint for the maintenance study to be clinical remission at week 44.[69]  I understand the time for the primary endpoint to be maintenance week 44 of the study of Example 2 and diagrammatically represented in Figure 1 of the specification as “Overall Exposure” Week 52.  In other words, the primary endpoint for the maintenance study of Example 2 is 52 weeks from induction week 0 as the period for the induction study was 8 weeks.

    [69] The specification at page 77, line 23.

24. The definition of clinical remission (and the testing procedure) in the US is different to that outside the US.  Two definitions of clinical remissions were applied to all subjects in the efficacy evaluation for the primary endpoint to accommodate the differences, these being:[70]

    [70] The specification at page 77, line 23 to page 78, line 2.

    ·The global definition stated as a Mayo score ≤2 points, with no individual subscore ˃1; and

    ·The US definition stated as an absolute stool number ≤3, a Mayo score rectal bleeding subscore of 0, and a Mayo endoscopy subscore of 0 or 1.

25. The efficacy results for clinical remission are described as follows:[71]

    [71] The specification at page 80, lines 21-28.

    ·Global definition: At week 44, the proportions of subjects in clinical remission were significantly greater in the ustekinumab q8w group and ustekinumab q12w group (43.8% and 38.4%, respectively) compared with subjects in the placebo group (24.0%; p<0.001 and p=0.002, respectively).

    ·US definition: At week 44, the proportions of subjects in clinical remission were significantly greater in the ustekinumab q8w group and ustekinumab q12w group (42.6% and 39.5%, respectively) compared with subjects in the placebo group (24.6%; p<0.001 and p=0.002, respectively).

1. Additionally, the specification reports:[72]

   [72] The specification at page 82, lines 4-11.

   “[a]pplying both global and US-specific definitions of clinical remission, the proportions of subjects achieving corticosteroid-free remission for at least 90 days prior to Week 44 was significantly greater (p<0.01) in the ustekinumab q8w and q12w groups compared with that in the placebo group.  Furthermore, among subjects receiving corticosteroids at maintenance baseline, significantly greater proportions of subjects (p<0.05) were in clinical remission and not receiving concomitant corticosteroids for at least 90 days prior to Week 44 in the ustekinumab q8w and q12w groups compared with those in the placebo group.”

2. The efficacy results are also described for other efficacy criteria including maintaining clinical response, achieving endoscopic healing, achieving histologic healing and achieving mucosal healing.[73]  Additionally, the results for the safety, pharmacokinetics and immunogenicity of administering ustekinumab subcutaneously are also reported.[74]

   [73] The specification at page 81, line 7 to page 82, line 4.

   [74] The specification at page 84, line 20 to page 88.

3. The specification states that the ustekinumab maintenance study provided evidence that the two dose regimens of administering 90 mg ustekinumab SC, q8w or q12w, were both effective in adult subjects with moderately to severely active UC who had responded to a single IV ustekinumab induction dose.[75]  Additionally, the safety and efficacy data from the maintenance study support a “positive benefit/risk profile for ustekinumab SC maintenance therapy.”[76]

   [75] The specification at page 88, lines 9-12.

   [76] The specification at page 88, lines 22-23.

4. The specification observes that STELARA® (ustekinumab) for the treatment of UC was approved in Europe as of 04 September 2019.[77].  Annex 1 of the opposed application reproduces the approved label (this being, the summary of product characteristics) for 130 mg (IV) STELARA®, and 45 mg or 90 mg (SC) STELARA®.[78]

   [77] The specification at page 89, lines 1-2.

   [78] The specification reproduces the summary of product characteristics for 130mg (IV) STELARA®, at at pages 90-112, and that for 45 mg or 90 mg (SC) STELARA® at pages 113-148.

   The invention as claimed

5. The correct approach to the construction of claims was discussed by Bennett J in H Lundbeck A/S v Alphapharm Pty Ltd. (Lundbeck):

   “the words in a claim should be read through the eyes of the skilled addressee in the context in which they appear … while the claims define the monopoly claimed in the words of the patentee's choosing, the specification should be read as a whole … it is not permissible to read into a claim an additional integer or limitation to vary or qualify the claim by reference to the body of the specification … terms in the claim which are unclear may be defined or clarified by reference to the body of the specification”[79]

   [79] [2009] FCAFC 70 at [118]-[120]; 81 IPR 228.

   Claim 1

6. It is convenient to parse claim 1, the first independent claims of the opposed application as follows:

   a)A method of treating moderately to severely active ulcerative colitis (UC) in a subject in need thereof, comprising

   b)administering to the subject a pharmaceutical composition comprising an effective amount of an anti-IL-12/IL-23p40 antibody,

   c)wherein the antibody comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region comprising: a complementarity determining region heavy chain 1 (CDRH1) amino acid sequence of SEQ ID NO:1; a CDRH2 amino acid sequence of SEQ ID NO:2; and a CDRH3 amino acid sequence of SEQ ID NO:3; and the light chain variable region comprising: a complementarity determining region light chain 1 (CDRL1) amino acid sequence of SEQ ID NO:4; a CDRL2 amino acid sequence of SEQ ID NO:5; and a CDRL3 amino acid sequence of SEQ ID NO:6,

   d)wherein after treating with the antibody, the subject is a responder to treatment by at least one measure of response to treatment

   e)selected from the group consisting of: (i) clinical remission based on at least one of the global definition of clinical remission with Mayo score ≤ 2 points with no individual subscore > 1 and the US definition of clinical remission with absolute stool number ≤ 3, rectal bleeding subscore of 0 and Mayo endoscopy subscore of 0 or 1, (ii) endoscopic healing with a Mayo endoscopy subscore of 0 or 1, (iii) clinical response based on the Mayo endoscopy subscore, (iv) mucosal healing, and (v) clinical response as determined by a decrease from baseline in the Mayo score by ≥30% and ≥3 points and a decrease from baseline in the rectal bleeding subscore ≥1 points or a rectal bleeding subscore of 0 or 1.

7. I will now consider the meaning of several terms of claim 1.

   A method of treating moderately to severely active ulcerative colitis (UC) in a subject in need thereof

8. The applicant submitted that:

   “the Specification is clearly directed to ‘clinically proven safe’ and ‘clinically proven effective’ methods of treating moderately to severely active UC.  These terms, and the term ‘clinically proven’, are defined in the Specification...As Prof. Ciorba explains, upon reading the Specification, it is apparent that:

   … to ‘treat’ a condition with a drug requires administering a drug that is known at that time to be capable of treating that condition in the relevant patient population.  A drug is only known to be capable of treating a condition if both its safety and efficacy have been established by Phase III clinical trial results ([except] where there is real world data collected from a large number of patients over a prolonged period of time that establishes safety and efficacy of that drug). [emphasis added]”[80]

   [80] The AS at [72] which refers to Ciorba at [230].

9. The opponent submitted that the applicant’s position is founded on:

   “the novel proposition that, in the context of the Application, ‘treating’ moderately to severely active UC involves administering a drug that is ‘known’ at the time of treatment to be safe and effective in a patient with moderately to severely active UC in the sense that the treatment had been the subject of a successful Phase III clinical trial.  Unsurprisingly, that proposition does not reflect any definition of ‘treating’ which is incorporated into the Application.  Nor does it reflect the plain and ordinary English meaning of the term ‘treating’ and normal use or understanding by any of the experts of the term.  Further, the proposition is inconsistent with established case law in this area concerning methods of treatment, which demonstrates that the disclosure of something much less than the results of a Phase III clinical trial can anticipate: e.g., even a clinical protocol, or hypothesis, without any results or proof: see Mylan Health Pty Ltd v Sun Pharma ANZ Pty Ltd (2020) 279 FCR 354 at [104]-[111], especially [104]-[106]. Similar attempts to support the novelty or inventiveness of claimed methods of treatment based on an artificially elevated construction of ‘treatment’ have failed in other cases: see e.g. Astellas Pharma Inc v Aragon Pharmaceuticals Inc [2022] APO 36 at [49]-[146]”[81]

   [81] The OS at [9].

10. The applicant also submitted that based on a consideration of the Delegate in Astellas Pharma Inc. v Aragon Pharmaceuticals, Inc. (Astellas) a claim to a method of treatment should be understood as referring only to use in a population as distinct from one or more individual acts of treatment.[82]

    [82] [2022] APO 36 at [103], [105].

11. At the oral hearing, the opponent submitted that such a construction would lead to an odd scenario where a claim to a method of treating a condition in a subject could not be considered an improvement unless there was improvement in subjects in a whole population.  The opponent also observed that the claims in the present case are directed to a method of treating a condition in a subject.  Additionally, the opponent submitted that a consideration based on the understanding in Astellas would be inconsistent with authorities and noted the finding of Nicholas J in Apotex Pty Ltd v Warner-Lambert Company LLC (No 2) (Warner-Lambert) who stated that “a claim will be infringed if a person administers a therapeutically effective amount of the relevant compound to a patient in need of treatment… for the purpose of providing such treatment even though the treatment may not be effective in that patient.”[83]

    [83] [2016] FCA 1238; 122 IPR 17 at [129]-[131].

12. The opponent also submitted that the fact that claims are to methods of treatment does not mean that the claimed responses must be achieved in every case and noted that Professor Pavli and Professor Ciorba agreed, as a matter of fact, that not all patients will respond to a particular treatment. [84]  Furthermore, the opponent observed the results of the studies described in the present application (which are the UNIFI Phase III clinical trials) demonstrate this fact.[85]

    [84] The OS at [47], citing Pavli #1 at 118(a) and Ciorba at [121].

    [85] Ibid.

13. While I understand I am to construe the claims in the context of the specification as a whole, it is “not legitimate to narrow or expand the boundaries of monopoly as fixed by the words of a claim by adding to those words glosses drawn from other parts of the specification.”[86]  The specification does describe examples of studies within a Phase III clinical trial to assess the efficacy of ustekinumab in human subjects with moderately to severely active UC.  However, the words of claim 1 do not limit the method (a) to a treatment method that has already been clinically proven to be safe and effective, or (b) to a treatment method that is performed on any patient population.  I would be impermissibly importing the requirements that the method be clinically proven on a patient population–in other words adding a gloss–if I were to adopt the applicant’s construction of “treat”.

    [86] Jupiters Ltd v Neurizons Pty Ltd [2005] FCAFC 90 at [67]; 65 IPR 86.

14. The Macquarie Dictionary defines “treat” as “to deal with (a disease, patient, etc) in order to relieve or cure”.[87]  Therefore, I interpret the plain meaning of the phrase “[a] method of treating moderately to severely active ulcerative colitis (UC) in a subject in need thereof” as indicating a method that is used with an intended purpose to relieve or cure a patient with moderately to severely active UC.

    [87] The Macquarie Dictionary Online, accessed 05 March 2025.

15. I also interpret the method of treatment defined in claim 1 to mean the treatment of one or more individuals suffering from moderately to severely active UC and is not limited to a subject population.

    administering to the subject a pharmaceutical composition comprising an effective amount of an anti-IL-12/IL-23p40 antibody

16. I consider the PSA reading the specification would interpret this phrase to mean a subject is administered a pharmaceutical composition with a monoclonal antibody or antigen binding fragment that binds to the 40 kDa (p40) subunit shared by cytokines interleukin-12 and interleukin 23 (IL-12/23p40).[88]  This antibody includes ustekinumab which was originally marketed by the applicant as Stelara®.[89]  From a plain meaning of the words, an “effective amount” of antibody is an amount that is intended to effectively treat moderately to severely active UC.

    [88] The specification at page 10, lines 19-22.

    [89] The specification at page 31, lines 16-18; Pavli #1 at [112], [280].

    wherein the antibody comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region comprising: a complementary determining region heavy chain 1 (CDRH1) amino acid sequence of SEQ ID NO:1; a CDRH2…of SEQ ID NO:2; and a CDRH3…of SEQ ID NO:3; and the light chain variable region comprising: a complementary determining region light chain 1 (CDRL1) amino acid sequence of SEQ ID NO:4; a CDRL2…of SEQ ID NO:5; and a CDRL3…of SEQ ID NO:6

17. I consider the PSA would understand the antibody of claim 1 to have a heavy chain variable region and a light chain variable region with the amino acid sequences as defined in the claim and with reference to the specification and sequence listing of the opposed application.

18. Professor Pavli observed that:

    (a)the amino acid sequences of SEQ ID NO:1 to No:3 (heavy chain CDRs) are present in SEQ ID NO:7 (heavy chain variable region), and the amino acid sequence of SEQ ID NO:7 is present in SEQ ID NO:10 (heavy chain);

    (b)the amino acid sequences of SEQ ID NO:4 to NO:6 (light chain CDRs) are present in SEQ ID NO:8 (light chain variable region), and the amino acid sequence of SEQ ID NO:8 is present in SEQ ID NO:11 (light chain);[90] and

    [90] Pavli #1 at [282].

    (c)ustekinumab comprises a heavy chain having the amino acid sequence of SEQ ID NO:10 and a light chain having an amino acid sequence of SEQ ID NO:11.[91]

    [91] Pavli#1 at [281], [254] and cites the specification at page 31, paragraph 3 and the sequence listing of opposed application.

19. Professor Pavli stated that he understands claim 1 to refer to an antibody having the same CDRs as ustekinumab and includes ustekinumab itself.  Additionally, Professor Pavli understands the antibody of claim 1 includes an antibody with the same variable regions as ustekinumab but with different constant regions to ustekinumab.  However, he stated that he was not aware that any such antibody had been developed before 24 September 2018 nor to the day he made his statement on 12 October 2023.[92]

    [92] Pavli #1 at [282].

20. Professor Ciorba also referred to the specification and sequence listing of the opposed application when commenting on the claim 1 and observed that SEQ ID NO:1 to NO:6 are the CDR sequences of the variable regions of the heavy and light chains of ustekinumab.[93]

    [93] Ciorba at [252].

21. I have reviewed the sequence listing and description of the opposed application, and I accept the explanations of Professor Pavli and Professor Ciorba regarding how the sequences defined in claim 1 relate to those of ustekinumab.  I interpret the scope of claim 1 includes ustekinumab itself and an antibody with the same six CDRs as ustekinumab.  I note that the specification uses ustekinumab and Stelara® interchangeably and describes ustekinumab (Stelara®) as comprising a heavy chain having the amino acid sequence of SEQ ID NO:10 and a light chain having an amino acid sequence of SEQ ID NO:11.[94]  I also note Stelara® is a commercial formulation of the antibody ustekinumab that was originally marketed by the applicant.[95]  I consider the skilled person would understand that ustekinumab and Stelara® refer to an antibody having the six CDRs sequences defined in claim 1.

    [94] The specification at page 3, lines 7 and 10; page 31, lines 16-18; page 89, line 1.

    [95] Pavli # 1 at [112].

22. Professor Ciorba also explained that generally the CDRs inform the binding specificity and affinity of an antibody molecule and antibodies with the same six CDRs would be expected to have the same binding specificity and affinity as ustekinumab.[96]

    [96] Ciorba at [74], [252].

23. During the oral hearing the opponent submitted that Professor Ciorba’s statement (at [74] of his evidence) that “[g]enerally speaking, the amino acid sequence of the CDRs informs the binding specificity and affinity of an antibody”, should not be understood as a universal proposition and that it will not always be true that antibodies with the same six CDRs would have the same specificity and affinity as ustekinumab.

24. This statement by Professor Ciorba was made in the context of providing the CGK about antibodies.  Therefore, I consider it is reasonable to interpret the statement as meaning that it was generally known and accepted, at the priority date of the opposed specification, that the amino acid sequence of the CDRs informs the binding specificity and affinity of an antibody.  My interpretation is consistent with the language used in the specification to describe the influence of CDRs on the binding capacity of an antibody.  The specification states that “[i]n general, the CDR residues are directly and most substantially involved in influencing antigen binding”.[97]  I also consider it is reasonable to interpret that an antibody with the same six CDR sequences as ustekinumab would be expected to have the same binding specificity and affinity as ustekinumab.

    [97] The specification at page 18, lines 20-21.

    wherein after treating with the antibody, the subject is a responder to treatment by at least one measure of response to treatment

25. I consider that it is reasonable to interpret this phrase in the context that the method of treatment is for the intended purpose of effectively relieving or curing a subject with moderately to severely active UC.  Firstly, I interpret the phrase to mean that after treating with the antibody, the intention is that the one or more subjects suffering from moderately to severely active UC show a measure of effectiveness to the treatment which is evaluated by at least one of the efficacy criteria defined.  Secondly, I consider that the claim does not define a requirement that at least one of the defined efficacy criteria will be achieved in every case and that every subject must be sorted into one of these criteria.  This is because in any given population there will be non-responders even in actual use.  For the purposes of interpretation, I consider it is sufficient that one or more subjects show a clinical response to treatment, as defined by the efficacy criteria.  My interpretation is consistent with the description in the specification where treatment with the antibody achieves a clinical response in some subjects but not others irrespective of the efficacy criteria being evaluated.  My interpretation is also consistent with evidence of Professor Ciorba and Professor Pavli who both stated that for each medication which was approved for UC before the priority date of the opposed application, there were some patients who did not respond to the medication.[98]

    [98] Ciorba at [121]; Pavli #2 at [62].

    selected from the group consisting of: (i) clinical remission based on at least one of the global definition of clinical remission with Mayo score ≤ 2 points with no individual subscore > 1 and the US definition of clinical remission with absolute stool number ≤ 3, rectal bleeding subscore of 0 and Mayo endoscopy subscore of 0 or 1, (ii) endoscopic healing with a Mayo endoscopy subscore of 0 or 1, (iii) clinical response based on the Mayo endoscopy subscore, (iv) mucosal healing, and (v) clinical response as determined by a decrease from baseline in the Mayo score by ≥30% and ≥3 points and a decrease from baseline in the rectal bleeding subscore ≥1 points or a rectal bleeding subscore of 0 or 1

26. Claim 1 defines five efficacy criteria by reference to indices for disease activity including a Mayo score, or a Mayo subscore.  I have previously discussed the Mayo score and Mayo subscores.

    Claims 2 and 3

27. Claims 2 and 3 are appended to claim 1.  I have previously explained how the various sequences defined in claims 1, 2 and 3 relate to one another and noted that ustekinumab (Stelara®) comprises a heavy chain having the amino acid sequence of SEQ ID NO:10 and a light chain having an amino acid sequence of SEQ ID NO:11.  Therefore, I interpret the antibody of claim 3 to be ustekinumab (Stelara®).

    Claims 4 and 5

28. Claims 4 and 5 are ultimately appended to claim 1.  I interpret the antibody of claim 4 to be in a pharmaceutical composition suitable for intravenous administration having a solution with the components defined in the claim.  I interpret the antibody of claim 5 to be in a pharmaceutical composition suitable for subcutaneous administration having a solution with the components defined in the claim.

    Claim 6

    …week 0 of the treatment

29. Claim 6 is appended to claim 4.  I consider the words of claim 6 define week 0 of the treatment as a time point when the first IV induction dose of the antibody is administered to the subject, this being at week 0 of the induction study.  The antibody is administered at a dosage of 6.0 mg/kg body weight of the subject or 130 mg, 260 mg, 390 mg or 520 mg per administration.  The antibody is in a pharmaceutical composition as defined in claim 4.

    Claim 7

    ….week 8 of the treatment

1. Claim 7 is appended to claim 6.  I interpret week 8 of the treatment to be eight weeks after the time point for the first IV dose defined in claim 6.  In other words, a SC dose of the antibody is administered to the subject eight weeks after week 0 of the induction study.  The antibody administered as a SC dose is in a pharmaceutical composition as defined in claim 5.

   Claims 8 and 9

2. Each of claims 8 and 9 is appended to claim 7.  I interpret the subject of claim 8 to have previously failed or was intolerant to at least one therapy from the five therapies defined in the claim or had demonstrated corticosteroid dependence.

3. I consider the words of claim 9 to define a treatment method that includes administering a maintenance dose every 8 weeks, or every 12 weeks, after the subcutaneous administration of the antibody at week 8 of the treatment defined in claim 7.

   Claims 10 to 16

   …44 weeks after week 0

4. Each of claims 10 to 16 is appended to claim 9.  The applicant submitted:

   “The experts disagree on the meaning of the phrase ‘44 weeks after week 0’ as used in claims 10-16 of the Opposed Application, although the Opponent also does not appear to press Prof. Pavli’s contorted construction of this term in the OS…

   Prof. Pavli asserts that this phrase is a reference to ‘44 weeks after the first dose of ustekinumab (i.e. the IV induction dose referred to in claim 6)’, despite acknowledging that this construction is inconsistent with the teaching of the Specification, and in particular ‘differs from the format of the UNIFI Phase III clinical trial, in which patients were assessed at 44 weeks after the first maintenance dose of ustekinumab’, and which is the subject of the Examples.

   Consistent with the evidence of Prof. Ciorba, a PSA would understand the term ‘44 weeks after week 0’, when read in the context of the Specification as a whole, to mean ‘44 weeks after the first maintenance dose’.  In particular, Prof. Ciorba states:

   As Prof. Pavli notes, in the UNIFI Phase III trial, as reflected in Examples 1 and 2 of the Opposed Application, ‘patients were assessed at 44 weeks after the first maintenance dose of ustekinumab’.  This is also consistent with Annex I, including Label Table 6, which refers to key efficacy measures at ‘week 44; 52 weeks from initiation of the induction dose’.  I also note that elsewhere the claims state ‘week 0 of the treatment’ when referring to the first induction dose (see claims 6, 19, 33 and 34).  Therefore, it is apparent to me that the reference to ‘at least 44 weeks after week 0’ (absent the qualifier ‘of the treatment’ following ‘week 0’) in claims 10-18 is a reference to at least 44 weeks after the first maintenance dose.

   It is also clearly the case that the feature ‘44 weeks after week 0’ presented some linguistic difficulty that this terminology attempts to avoid.  This is apparent from Figure 1, which shows that subjects who achieved a clinical response at week 8 and at week 16 of the Induction Study entered the Maintenance Study.

   The Applicant submits that the evidence of Prof. Ciorba should be preferred because it represents a whole of specification approach to claim construction that involves construing the claims in ‘a practical, commonsense manner’.”[99]

5. The opponent submitted during the oral hearing that it adopts Professor Pavli’s interpretation of the phrase “44 weeks after week 0”.[100]  I also observe that Professor Pavli noted that “[presently amended claims 10-16] do not refer to 44 weeks of maintenance therapy, or 44 weeks after week 0 of maintenance therapy.”[101]

6. I tend to be of the view that if the patentee had intended week 0 of claim 10-16 to be week 0 of the maintenance therapy, the words of the claims should have been chosen to reflect this qualification.  I would be impermissibly importing a gloss from the figures and examples of the specification if I were to interpret “44 weeks after week 0” of claims 10-16 to be 44 weeks after week 0 of the maintenance therapy.

7. As there is no qualifier in the claims that week 0 is week 0 of the maintenance therapy, the plain meaning of the words indicates to me that week 0 of claim 10-16 is the time when the first IV induction dose of the antibody is administered to the subject.  In other words, week 0 of the treatment as defined in claim 6.  My interpretation would be consistent with the structure of the claim appendencies.  Additionally, claim 10 defines “week 16 of the treatment” which I interpret to be a time 16 weeks after the first IV dose as defined in claim 6.  Therefore, it seems reasonable to me that the same starting time point is intended for week 16 and week 0 in claim 10 and claims 11-16.  I consider this to be a case where “the language of the claim must be understood to mean what it actually says”.[102]

   [99] The AS at [83]-[87] citing Pavli #1 at [308], Pavli #2 at [130], Ciorba at [255] and the specification at page 75, lines 14-25.

   [100] Pavli #1 at [308], Pavli #2 at [130].

   [101] Pavli #1 at [308].

   [102] GlaxoSmithKline Consumer Healthcare Investments (Ireland) (No 2) Limited v Generic Partners Pty Limited [2018] FCAFC 71; 131 IPR 384 at [121], [139].

100. I interpret the phrase “44 weeks after week 0” of claims 10-16 to be 44 weeks after the first IV dose of the antibody is administered to the subject as defined in claim 6.

Claim 11

…corticosteroid-free clinical remission

101. I consider the plain meaning of the phrase to be that the subject in clinical remission is not receiving concurrent corticosteroids to prevent the return of the symptoms of UC.  I note that my interpretation of the phrase is consistent with the definition of this efficacy criteria provided in the specification.[103]

Claim 17

[103] The specification at page 78, lines 6-7.

102. Claim 17 is a second independent claim to a method of treating moderately to severely active UC in a subject.  I interpret the subject of claim 17 to be one or more individuals suffering from moderately to severely active UC and is not limited to a subject population.  Additionally, I interpret the subject to be one who (a) had previously failed or was intolerant to at least one therapy from the five therapies defined in the claim, or (b) had demonstrated corticosteroid dependence.  The therapies which the subject had failed or was intolerant to are (i) an anti-TNF (anti- Tumor Necrosis Factor), (ii) vedolizumab (an integrin antagonist). (iii) corticosteroids, (iv) azathioprine (AZA), and (v) 6 mercaptopurine (6 MP).

103. In the treatment method of claim 17, the subject is

·(a) administered an intravenous dose of an anti-IL-12/IL-23p40 antibody at week 0 of the treatment, and

·(b) administered a subcutaneous dose of the same anti-IL-12/IL-23p40 antibody at week 8 of the treatment.

I interpret the anti-IL-12/IL-23p40 antibody of claim 17 to be defined in identical terms as the antibody in claim 1, that is with identical CDR sequences on the heavy and light chain variable regions as those defined for claim 1.  The quantity of the intravenous dose of anti-IL-12/IL-23p40 antibody at week 0 is defined in identical terms to the dose defined in claim 6.  The quantity of the subcutaneous dose of anti-IL-12/IL-23p40 antibody at week 8 is defined in identical terms to the dose defined in claim 7.  I interpret the scope of claim 17 to include an antibody with the same six CDRs as ustekinumab and includes ustekinumab itself.

104. The subject of claim 17 is defined to be a responder to treatment by at least one measure of response to treatment.  For the same reasons as discussed for claim 1, I interpret that after administering the antibody, the intention is that one or more subjects suffering from moderately to severely active UC show a measure of effectiveness to the treatment which is evaluated by at least one of the efficacy criteria defined.  Noting that there will be non-responders to treatment in any given population, as I previously discussed, I also consider that the claim does not define a requirement that at least one of the defined efficacy criteria will be achieved in every case and that every subject must be sorted into one of these criteria.

Claims 18-21

105. Claims 18-21 are ultimately appended to claim 17 and define features in addition to those in claim 17.  The antibody of claims 18 and 19 are defined in identical terms to the antibody in claims 2 and 3, respectively.  The pharmaceutical composition of claim 20 is defined in identical terms as the composition of claim 4 which is suitable for intravenous administration.  The pharmaceutical composition of claim 21 is defined in identical terms as the composition of claim 5 which is suitable for subcutaneous administration.

Claims 22-27

106. Claims 22-27 are appended to claim 17 and each appended claim defines that the intended response is that the subject demonstrates a specific efficacy criterion by week 16 of the treatment, that is any time before and until week 16 of the treatment.  I interpret “week 16 of the treatment” to be 16 weeks after the subject is administered an intravenous dose of anti-IL-12/IL-23p40 antibody at week 0.

107. I consider that the skilled person would interpret “endoscopic healing” defined in claim 23 as improvement of the mucosal appearance as assessed by endoscopy.  This is because endoscopic appearance of the mucosa is a component of the full Mayo score which is part of the CGK.[104]

[104] Pavli # 1 at [91].

108. I consider the plain meaning of “mucosal healing” defined in claim 25 means healing of the mucosa as assessed by any method well understood by the skilled person.  This includes endoscopic assessment but is not limited to an improvement of the endoscopic mucosal appearance.  For example, the specification describes histological healing of the mucosa and explains this is based on the Geboes score.[105]  Professor Pavli stated that the Geboes score is widely known and generally accepted and used in Australia and overseas as criteria for UC clinical trials before the priority date.[106]

Claim 28

[105] The specification at page 67, lines 1-8.

[106] Pavli # 1 at [269].

109. Claim 28 is appended to claim 17.  I interpret the subject of claim 28 not to have shown a measure of effectiveness to treatment with the antibody, as evaluated by the five efficacy criteria defined in claim 17, by week 8 but does show a measure of effectiveness to treatment with the antibody by week 16.  I interpret “week 8” and “week 16 of the treatment” in claim 28 to be the number of weeks after week 0 when the subject is administered an intravenous dose of anti-IL-12/IL-23p40 antibody.

Claim 29

110. Claim 29 is a third independent claim to a method of treating moderately to severely active UC in a subject.  In the treatment method of claim 29, I interpret the subject is

·(a) administered an intravenous dose of an anti-IL-12/IL-23p40 antibody at week 0 of the treatment, and

·(b) administered a subcutaneous dose of the same anti-IL-12/IL-23p40 antibody at week 8 of the treatment, and

·(c) provided a maintenance therapy for 44 weeks following the subcutaneous dose of the antibody administered in step (b), and

·(d) it is the intention that one or more subjects show a measure of effectiveness to the treatment which is evaluated by at least one of the efficacy criteria defined, noting that there will be non-responders to treatment in any given population.

111. I interpret the maintenance therapy of claim 29 to comprise an administration of a subcutaneous dose of the anti-IL-12/IL-23p40 antibody at a dosage of 90 mg per administration, once every 8 weeks or once every 12 weeks, in the 44-week period after week 8 of the treatment.  Where the maintenance therapy is provided once every 8 weeks, the scope of claim 29 includes administration of a subcutaneous dose of the antibody 16, 24, 32 and 40 weeks after week 0 of the treatment.  Where the maintenance therapy is provided once every 12 weeks, the scope of claim 29 includes administration of a subcutaneous dose of the antibody 20, 32 and 44 weeks after week 0 of the treatment.  This is illustrated in Figure 1 of the opposed application.

112. I interpret the anti-IL-12/IL-23p40 antibody of claim 29 to be defined in identical terms as the antibody in claim 1, that is with identical CDR sequences on the heavy and light chain variable regions as those defined for claim 1.  The quantity of the intravenous dose of anti-IL-12/IL-23p40 antibody administered at week 0 is defined in claim 29 in identical terms to the dose defined in claim 6.  The quantity of the subcutaneous dose of anti-IL-12/IL-23p40 antibody administered at week 8 is defined in claim 29 in identical terms to the dose defined in claim 7.  I interpret the scope of claim 29 to include an antibody with the same six CDRs as ustekinumab and includes ustekinumab itself.

Claim 30

113. Claim 30 is a fourth independent claim to a method of treating moderately to severely active UC in a subject.  In the treatment method of claim 30, I interpret the subject is

·(a) administered an intravenous dose of an anti-IL-12/IL-23p40 antibody at week 0 of the treatment, and

·(b) administered a subcutaneous dose of the same anti-IL-12/IL-23p40 antibody at week 8 of the treatment, and

·(c) administered a maintenance therapy following the subcutaneous dose of the antibody administered in step (b), and

·(d) it is the intention that one or more subjects show a measure of effectiveness to the treatment which is evaluated by at least one of the efficacy criteria defined, noting that there will be non-responders to treatment in any given population.

114. I interpret the anti-IL-12/IL-23p40 antibody of claim 30 to be defined in identical terms as the antibody in claim 2; that is, with the heavy chain variable regions of amino acid sequence of SEQ ID NO:7 and light chain variable regions of amino acid sequence of SEQ ID NO:8.  Since the amino acid sequences of SEQ ID NO:7 and SEQ ID NO:8 are, respectively, present in the heavy chain and the light chain of ustekinumab, I interpret the scope of claim 30 to include an antibody with the same six CDRs as ustekinumab and includes ustekinumab itself.

115. The quantity of the intravenous dose of anti-IL-12/IL-23p40 antibody administered at week 0 is defined in claim 30 in identical terms to the dose defined in claim 6.  The quantity of the subcutaneous dose of anti-IL-12/IL-23p40 antibody administered at week 8 is defined in claim 30 in identical terms to the dose defined in claim 7.

116. I interpret the maintenance therapy of claim 30 to comprise an administration of an additional subcutaneous doses of the same anti-IL-12/IL-23p40 antibody as administered in step (b) which is provided at a dosage of 90 mg per administration.  The antibody is administered once every 8 weeks, or once every 12 weeks, after week 8 of the treatment.  Unlike claim 29, claim 30 does not limit the period of the maintenance therapy.  For example, the scope of claim 30 includes (1) an additional subcutaneous dose of the antibody 16, 24, 32, 40, 48 or 56 weeks after week 0 of the treatment, where the maintenance therapy is provided once every 8 weeks, or (2) an additional subcutaneous dose of the antibody 20, 32, 44, 56 or 68 weeks after week 0 of the treatment, where the maintenance therapy is provided once every 12 weeks.

Novelty

117. It is a requirement of subsection 18(1) of the Act that the invention, so far as claimed in any claim, is novel. Subsection 7(1) states that an invention is taken to be novel unless it is not novel in the light of the prior art base as it stood before the priority date. For the purposes of the present consideration, the following kinds of information are relevant:

·Prior art information made publicly available in a single document; and

·Prior art information made publicly available in two or more related documents if the relationship between the documents is such that a person skilled in the relevant art would treat them as a single source of that information

118. It is well established that the general test for lack of novelty is the reverse infringement test.  The classic formulation of this test is that given by Aickin J in Meyers Taylor Pty Ltd. v Vicarr Industries Ltd.:

“The basic test for anticipation or want of novelty is the same as that for infringement and generally one can properly ask oneself whether the alleged anticipation would, if the patent were valid, constitute an infringement”[107]

[107] [1977] HCA 19 at [20]; 137 CLR 228 at 235.

119. This test is satisfied if the alleged anticipation discloses all the essential features of the invention as claimed.[108]

[108] Nicaro Holdings Pty Ltd v Martin Engineering Co [1990] 91 ALR 513 at 517; 16 IPR 545.

120. Australian courts have often identified the principles of the UK Court of Appeal in The General Tire & Rubber Company v The Firestone Tyre and Rubber Company Limited[109] (the General Tire case) as the criteria for determining anticipation by a prior publication.  Most relevantly, to anticipate the patentee’s claim the prior publication must contain clear and unmistakable directions to do what the patentee claims to have invented:

“If the prior inventor’s publication contains a clear description of, or clear instructions to do or make, something that would infringe the patentee’s claim if carried out after the grant of the patentee’s patent, the patentee’s claim will have been shown to lack the necessary novelty, that is to say, it will have been anticipated. … if carrying out the directions contained in the prior inventor’s publication will inevitably result in something being made or done which, if the patentee’s patent were valid, would constitute an infringement of the patentee’s claim, this circumstance demonstrates that the patentee’s claim has in fact been anticipated.

If, on the other hand, the prior publication contains a direction which is capable of being carried out in a manner which would infringe the patentee’s claim, but would be at least as likely to be carried out in a way which would not do so, the patentee’s claim will not have been anticipated … To anticipate the patentee’s claim the prior publication must contain clear and unmistakeable directions to do what the patentee claims to have invented.” ^[110]

[109] [1972] RPC 457 at 485-486.

[110] Ibid.

121. In Novozymes A/S v Danisco A/S, Jessup J stated that the inevitability of outcome to which the General Tire case refers must be such as would arise from recourse to information referred to in subsection 7(1) of the Act:

“the inevitability of outcome to which General Tire refers must be such as would arise from recourse to the information referred to in the section. At the expense of repetition, it is here useful to remind ourselves of what the Court of Appeal said in that case ([1972] RPC at 485-486):

… if carrying out the directions contained in the prior inventor's publication will inevitably result in something being made or done which, if the patentee's patent were valid, would constitute an infringement of the patentee's claim, this circumstance demonstrates that the patentee's claim has in fact been anticipated.  [Emphasis added] 

This proposition is explicitly hypothetical.  It is concerned not with what has happened or with what could have happened, but with what would have happened if the directions were carried out.  As such, the proposition is in complete harmony with s 7(1), and with every other presently relevant aspect of the jurisprudence in this area.  It is not the doing of it, nor even the ability to do it, that amounts to anticipation:  it is the content of the information.  If the information contains directions which, if carried out, would constitute an infringement of the patent in suit, the invention under the latter is not novel.”[111] [Emphasis in original]

[111] [2013] FCAFC 6 at [177]; 99 IPR 417.

122. The Full Court in Mylan Health Pty Ltd v Sun Pharma ANZ Pty Ltd (the Mylan case) held that a clinical trial protocol (the Accord Protocol) without scientific proof or substantiation anticipated a claimed invention:

Conclusion on obviousness in light of CGK alone

[258] [2024] FCAC135 at [92]; 183 IPR 309.

255. I consider the opponent has not established that when considering the CGK alone, the PSA would be directly led as a matter of course to select only ustekinumab to treat moderately to severely active UC in the expectation that doing so might well produce a useful alternative to the prior art.  Consequently, I conclude that the opponent has not established that any of the claims of the opposed application lacks an inventive step in light of CGK alone before the priority date of the claims.

Obviousness in light of citations considered together with CGK

256. The opponent relies on the following documents to allege lack of inventive step:

·CTR 236;

·Abstract P759

·DDW Poster; and

·Abstract Tu1713.[259]

[259] The OS at [138]-[142].

Obviousness in light of CTR 236 considered together with common general knowledge

257. I have previously found that the disclosure of CTR 236 anticipates claims 1-3, 6-19 and 22-30 of the opposed application.  Relevant for the present purposes, there is a clear teaching of a deliberate administration of ustekinumab for the intended purpose of treating moderately to severely active UC to achieve the intended results claimed in the claims.  It follows from the discussion that each of claims 1-3, 6-19 and 22-30 lacks an inventive step in light of CTR 236 considered together with CGK.

Claims 4, 5, 20 and 21

258. CTR 236 does not disclose ustekinumab formulated with the claimed excipients.  However, before 24 September 2018, it is a fact that Stelara® was the only ustekinumab formulation that had obtained regulatory approval and marketed by Janssen.[260]  The Stelara® IV and SC formulations had the claimed excipients.[261]  The question for the purpose of inventive step is whether it would have been a matter of routine for a skilled person to use Stelara® in the UNIFI Phase III clinical trials.

[260] Pavli #1 at [186]; Pavli #2 at [34]; Ciorba at [75].

[261] Pavli # 1 at [288]-[291]; Kayser at [44]-[55].

259. Professor Pavli stated that as a practical matter an antibody must be formulated to be administered to a patient (e.g., with other constituents put into a liquid formulation for IV infusion or SC injection).  He also stated that given that Janssen was the sponsor of the UNIFI Phase III clinical trials, he understood the references to the administration of ustekinumab in CTR 236 to be references to the administration of Stelara®.[262]

[262] Pavli # 1 at [186].

260. I consider it is reasonable to infer from Professor Pavli’s evidence that it would be a matter of routine for a skilled person to use Stelara® in the methods taught by CTR 236 since this was the only ustekinumab formulation which was approved for administration in humans at the priority date.  Professor Pavli stated that gastroenterologists, including himself, would refer to Product Information documents or equivalent documents approved by the regulator of the relevant country (e.g., “Labels” approved by the FDA) for information regarding the medications.  He further stated that if provided with any of CTR 236, Abstract P759, the DDW Poster and Abstract Tu1713, he would have read each of the documents together with the Stelara 2017 PI. [263]  I understand Professor Pavli to mean that it was standard practice for a skilled person to combine the information in the Stelara 2017 PI, which included the IV and SC formulations, with the information disclosed in any one of the prior art citations.[264]  Therefore, I consider that the skilled person, having led as a matter of routine to use Stelara® in the UNIFI Phase III clinical trials, would also arrive at method of administering ustekinumab with the excipients as claimed in each of claims 4, 5, 20 and 21.  Consequently, I conclude that each of claims 4, 5, 20 and 21 lacks inventive step in light of CTR 236 considered together with CGK.

Conclusion on obviousness in light of CTR 236 considered together with CGK

[263] Pavli # 1 at [208], [234].

[264] The Stelara® IV and SC formulations are disclosed on pages 1-2 of the Stelara 2017 PI.

261. I conclude that each of claims 1-30 lacks inventive step in light of CTR 236 considered together with CGK.

Obviousness in light of Abstract P759 considered together with common general knowledge

262. I have previously found that the disclosure of Abstract P759 anticipates claims 1-9, 17-28 and 30.  Relevant for the present purposes, there is a clear teaching of a deliberate administration of ustekinumab for the intended purpose of treating moderately to severely active UC to achieve the intended results claimed in the claims.  It follows from the discussion that claims 1-9, 17-28 and 30 lack an inventive step in light of Abstract P759 considered together with the CGK.

Claims 10-16

263. I have previously found Abstract P759 to disclose that clinical remission was achieved in some patients by week 16 after the first IV dose of ustekinumab, but there is no disclosure that clinical remission continues at least 44 weeks after the first IV dose of ustekinumab.

264. Professor Pavli stated that he would have expected some participants treated with ustekinumab in accordance with the dosage regime set out in Abstract P759 to have achieved clinical remission by week 16 and continued to remain in clinical remission (1) until at least 44 weeks after the first IV induction dose of the ustekinumab, as well as (2) until at least 44 weeks after the first maintenance dose of ustekinumab (this being 52 weeks after the first IV induction dose of ustekinumab).[265]

[265] Pavli # 1 at [333], [335].

265. Professor Ciorba stated that periods of remission amongst CD and UC patients can vary, lasting weeks, months or years.  However, Professor Ciorba also stated that patients typically experience relapsing disease, which involves periods of active disease (“flares”) alternating with periods of remission.[266]

[266] Ciorba at [37], [40].

266. The question for the purposes of inventive step is whether a skilled person would have as a matter of routine continued antibody treatment with an expectation that clinical remission would continue in some subjects, for at least 44 weeks after the first IV dose of antibody, in light of the disclosure in Abstract P759.  I consider that it is reasonable to infer from the evidence of the expert witnesses that the answer is yes.  Therefore, I conclude that each of claims 10-16 lacks an inventive step in light of Abstract P759 considered together with CGK.

Claim 29

267. Whilst Abstract P759 does not explicitly disclose a maintenance period of 44 weeks, the disclosure does not limit the number of repeats of the maintenance dose (this being 90 mg ustekinumab as a SC injection every 8 weeks).  The median follow-up period was disclosed as 27 weeks with a range of 15-40 weeks.  Therefore, I consider it is reasonable that the skilled person would understand that Abstract P759 teaches a maintenance period of various lengths.  However, I consider the evidence does not establish that it would be a matter of routine for the skilled person to use a maintenance period of 44 weeks.  Consequently, I conclude it has not been established that claim 29 lacks an inventive step in light of Abstract P759 considered together with CGK.

Conclusion on obviousness in light of Abstract P759 considered together with CGK

268. I conclude that each of claims 1-28 and 30 lacks inventive step in light of Abstract P759 considered together with CGK.  However, it has not been established that claim 29 lacks an inventive step in light of Abstract P759 considered together with CGK.

Obviousness in light of DDW Poster considered together with common general knowledge

269. I have previously found that the disclosure of DDW Poster anticipates claims 1-9, 17-28 and 30 as there is a clear teaching of a deliberate administration of ustekinumab for the intended purpose of treating moderately to severely active UC to achieve the intended results claimed in these claims.  It follows from the discussion that claims 1-9, 17-28 and 30 lack inventive step in light of the DDW Poster considered together with the CGK.

Claims 10-16 and 29

270. I have previously found that the disclosure of DDW Poster is very similar to that of Abstract P759.  Therefore, the same analyses for assessing inventive step that I considered for Abstract P759 concerning claims 10-16 and 29 apply to the DDW Poster.  It follows that, for the same reasons provided for Abstract P759, I conclude that each of claims 10-16 lacks inventive step in light of the DDW Poster considered together with the CGK.  However, it has not been established that claim 29 lacks an inventive step in light of the DDW Poster considered together with the CGK.

Conclusion on obviousness in light of the DDW Poster considered together with CGK

271. I conclude that each of claims 1-28 and 30 lacks inventive step in light of the DDW Poster considered together with the CGK.  However, it has not been established that claim 29 lacks an inventive step in light of the DDW Poster considered together with the CGK.

Obviousness in light of Abstract Tu1713 considered together with common general knowledge

272. Since the disclosure in Abstract Tu1713 is virtually identical to Abstract P759, the same analyses I considered for Abstract P759 applies to Abstract Tu1713.  It follows that, for the same reasons as provided for Abstract P759, I conclude that claims 1-28 and 30 lack inventive step in light of Abstract Tu1713 considered together with CGK.  However, it has not been established that claim 29 lacks an inventive step in light of the Abstract Tu1713 considered together with the CGK.

Conclusion on obviousness

273. I conclude that each of claims 1-30 of the opposed application lacks inventive step in light of cited prior art considered together with CGK.

Support

274. Section 40(3) of the Act requires that the claims must be supported by matter disclosed in the specification.  Burley J considered the requirement of support in Merck Sharp & Dohme Corporation v Wyeth LLC (No 3) (Merck) and noted the claims will be appropriately supported if they “correspond to the technical contribution to the art”.[267]

[267] [2020] FCA 1477; 155 IPR 1 at [530]-[531] citing Walker LJ in Generics UK(HL) at 19 who referenced Fuel Oils/EXXON (T409/91) [1994] OJ EPO 653 (Exxon) at 659.

275. The technical contribution to the art is a subtle concept that is not to be confused with the inventive concept that is often discussed in relation to inventive step.  The distinction was explained by Walker LJ in Generics (UK) Limited v H Lundbeck A/S [2009] UKHL 12 (Generics UK(HL)):

“The expressions are certainly connected, but I do not think it is helpful (either in considering Lord Hoffmann's opinion, or generally) to treat them as having precisely the same meaning.  ‘Inventive concept’ is concerned with the identification of the core (or kernel, or essence) of the invention – the idea or principle, of more or less general application (see Kirin-Amgen [2005] RPC 9 paras 112-113) which entitles the inventor’s achievement to be called inventive. The invention’s technical contribution to the art is concerned with the evaluation of its inventive concept – how far forward has it carried the state of the art? The inventive concept and the technical contribution may command equal respect but that will not always be the case.”[268]

[268] Generics UK(HL) at [30].

276. An important question will often be whether the technical contribution to the art is a general principle or the specific examples in the specification.  Lord Hoffmann gave some examples in Biogen v Medeva Plc [1997] RPC 1 (Biogen):

“Thus if the patentee has hit upon a new product which has a beneficial effect but cannot demonstrate that there is a common principle by which that effect will be shared by other products of the same class, he will be entitled to a patent for that product but not for the class, even though some may subsequently turn out to have the same beneficial effect.  On the other hand, if he has disclosed a beneficial property which is common to the class, he will be entitled to a patent for all products of that class (assuming them to be new) even though he has not himself made more than one or two of them.”[269]  [citations omitted]

[269] Biogen at 49.

277. In Merck Burley J referred to CSR Building Products Limited v United States Gypsum Company [2015] APO 72 (CSR), where the delegate adopted the summary provided by Aldous J in Schering Biotech Corp’s Application, [1993] RPC 249 at 252-253, to answer the question of the claim support obligation:

“… to decide whether the claims are supported by the description it is necessary to ascertain what is the invention which is specified in the claims and then compare that with the invention which has been described in the specification.  Thereafter the court’s task is to decide whether the invention in the claims is supported by the description.  I do not believe that the mere mention in the specification of features appearing in the claim will necessarily be a sufficient support.  The word ‘support’ means more than that and requires the description to be the base which can fairly entitle the patentee to a monopoly of the width claimed.”[270]

[270] Merck at [546].

278. Burley J stated:

“That approach encapsulates broadly the claim support obligation under s 40(3). To it may be added the requirement that the technical contribution to the art must be ascertained. Where it is a product, it is that which must be supported in the sense that the technical contribution to the art disclosed by the specification must justify the breath of the monopoly claimed.”[271]

[271] Merck at [547].

279. The considerations for the approach as stated in CSR, which the Federal Court have approved, are:

“i) construe the claims to determine the scope of the invention as claimed,
 ii) construe the description to determine the technical contribution to the art, and

[272] CSR at [115].

iii) decide whether the claims are supported by the technical contribution to the art.”[272]

The opponent’s allegations

280. The opponent alleged that the claims of the opposed application include use of any anti-IL-12/IL-23p40 antibody having the same CDRs as ustekinumab to treat UC but the disclosure in the specification does not extend beyond ustekinumab.  The opponent also alleged that the scope of the claims includes an antibody with an altered Fc region which can play a role in pharmacokinetics and bioavailability.  Therefore, the opponent alleged that the work involved in identifying any other antibody which would work in the claimed method involves undue experimentation.  Consequently, the opponent alleged that a claim to any other antibody, apart from ustekinumab, exceeds the technical contribution of the application and lacks support.[273]

[273] The OS at [149]; the ORS at [39]-[40]; the OPHS at [26]-[30].

281. The opponent’s allegations rely on:

·Professor Pavli’s understanding that claim 1 includes ustekinumab itself and also an antibody with the same variable regions as ustekinumab but with different constant regions as ustekinumab; [274] and

·Professor Ciorba’s explanation of the typical structure of antibodies which included the following observations:

“…Generally speaking, the amino acid sequence of the CDRs informs the binding specificity and affinity of the antibody molecule.  The stem of the Y-shaped antibody structure is the Fragment Crystallizable (Fc) region, formed by the constant regions of the heavy chains, and is responsible for antibody effector function, as the region interacts with Fc receptors and complement proteins.  The Fc region is typically not important for targeting and neutralising soluble antigens, including soluble inflammatory cytokines.  However, the Fc region can play a role in pharmacokinetics / bioavailability.”[275] (bold font in original)

[274] Pavli # 1 at [282].

[275] Ciorba at [74].

What is the technical contribution to the art?

282. While the examples in the opposed specification describe the use of ustekinumab to treat moderately to severely active UC, the specification also provides a general disclosure that antibodies with the same six CDRs as ustekinumab can be used to treat the condition.  As previously discussed, the specification uses the term “anti-IL-12/IL-23p40 antibody” to refer to a monoclonal antibody (mAb) or antigen binding fragment thereof, that binds to the 40 kDa (p40) subunit shared by cytokines interleukin-12 and interleukin 23 (IL-12/23p40).[276]  Ustekinumab (STELARA®) is an embodiment of such a mAb and prevents IL-12 and IL-23 bioactivity by inhibiting their interaction with the cell surface IL-12Rß1 receptor protein.  Ustekinumab effectively neutralises IL-12 (Th1)- and IL-23 (Th17)-mediated cellular responses through this mechanism of action.[277]

[276] The specification at page 10, lines 19-22.

[277] The specification at page 3, lines 7-12 and page 31, lines 16-18.

283. I have also previously found that an antibody with the same six CDR sequences as ustekinumab would be expected to have the same binding specificity and affinity as ustekinumab.  Furthermore, the specification states that the affinity of an antibody can be tested using methods that are known to the skilled person.[278]  Therefore, I consider the technical contribution to the art is the use of an anti-IL-12/IL-23p40 antibody having the six defined CDRs sequences (these being amino acid sequences SEQ ID NO: 1 to SEQ ID NO: 6) to bind to the common p40 subunit of IL-12 and IL-23 and thereby neutralise the cellular responses mediated by these cytokines.

[278] The specification at page 25, lines 11-19.

284. While the specification states that certain embodiments of the antibody comprise an altered (e.g. mutated) Fc region to reduce or enhance the effector function of the antibody, the specification also discloses that effector functions can be assessed using various assays, for example Fc binding assays, ADCC assays, CDC assays, etc.[279]  I consider that a skilled person would understand the specification to teach that assays for testing effector functions are generally known and part of routine experimentation.

[279] The specification at page 20, lines 17-23; page 21 lines 1-9.

285. Therefore, while the inclusive nature of the term “comprising” means the claims can include an altered Fc region, I consider that the work involved in identifying an antibody with an altered Fc region which would work in the claimed method would be part of routine experimentation a skilled person can expect to perform.

286. I also note that apart from Professor Ciorba’s statement regarding the role of the Fc region (which was made in the context of explaining the structure of an antibody), there is no evidence that there were in fact issues of pharmacokinetics and bioavailability which involve undue experimentation.  Therefore, I consider the opponent has not discharged its burden of proof that the work involved in identifying whether any other antibody, apart from ustekinumab, would work in the claimed method involves undue experimentation.

Are the claims supported?

287. I have previously interpreted the scope of independent claims 1, 17, 29 and 30 to include use of an antibody with the same six CDRs as ustekinumab, and ustekinumab itself, in a method of treating UC.  Since the amino acid sequence of the CDRs informs the binding specificity and affinity of the antibody molecule, I consider the scope of claims 1, 17, 29 and 30 corresponds to the technical contribution to the art.

288. I also consider the scope of the appended claims 2-16 and 18-28 corresponds to the technical contribution to the art for similar reasons as discussed for the independent claims.

289. Consequently, I conclude that the opponent has not established that any of the claims lack support from the subject matter disclosed in the opposed application.

Conclusion

290. Each of claims 1-30 of the opposed application lacks novelty in view of the cited prior art.  Each of claims 1-30 of the opposed application lacks inventive step in light of cited prior art considered together with CGK.

291. It has not been established that any of the claims lack support from the subject matter disclosed in the opposed application.

292. While not certain, it is possible that there is subject matter disclosed in the specification which could be used as a basis to amend the claims to overcome my findings.  Consequently, Janssen Biotech, Inc. is given two months from the date of this decision to propose suitable amendments.

Costs

293. It is normal that costs should follow the event.  I see no reason to depart from that result.  Costs according to Schedule 8 are awarded against Janssen Biotech, Inc..

Dr A. Lim
Delegate of the Commissioner of Patents

Annex A:  The claims of the opposed specification

1. A method of treating moderately to severely active ulcerative colitis (UC) in a subject in need thereof, comprising administering to the subject a pharmaceutical composition comprising an effective amount of an anti-IL-12/IL-23p40 antibody, wherein the antibody comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region comprising: a complementarity determining region heavy chain 1 (CDRH1) amino acid sequence of SEQ ID NO:1; a CDRH2 amino acid sequence of SEQ ID NO:2; and a CDRH3 amino acid sequence of SEQ ID NO:3; and the light chain variable region comprising: a complementarity determining region light chain 1 (CDRL1) amino acid sequence of SEQ ID NO:4; a CDRL2 amino acid sequence of SEQ ID NO:5; and a CDRL3 amino acid sequence of SEQ ID NO:6, wherein after treating with the antibody, the subject is a responder to treatment by at least one measure of response to treatment selected from the group consisting of: (i) clinical remission based on at least one of the global definition of clinical remission with Mayo score ≤ 2 points with no individual subscore > 1 and the US definition of clinical remission with absolute stool number ≤ 3, rectal bleeding subscore of 0 and Mayo endoscopy subscore of 0 or 1, (ii) endoscopic healing with a Mayo endoscopy subscore of 0 or 1, (iii) clinical response based on the Mayo endoscopy subscore, (iv) mucosal healing, and (v) clinical response as determined by a decrease from baseline in the Mayo score by ≥30% and ≥3 points and a decrease from baseline in the rectal bleeding subscore ≥1 points or a rectal bleeding subscore of 0 or 1.

2. The method of claim 1, wherein the antibody comprises the heavy chain variable region of the amino acid sequence of SEQ ID NO:7 and the light chain variable region of the amino acid sequence of SEQ ID NO:8.

3. The method of claim 1, wherein the antibody comprises a heavy chain of the amino acid sequence of SEQ ID NO:10 and a light chain of the amino acid sequence of SEQ ID NO:11.

4. The method of any one of claims 1-3, wherein the antibody is in a pharmaceutical composition for intravenous administration comprising a solution comprising 10 mM L-histidine, 8.5% (w/v) sucrose, 0.04% (w/v) polysorbate 80, 0.4 mg/mL Lmethionine, and 20 μg/mL EDTA disodium salt, dehydrate, at pH 6.0.

5. The method of any one of claims 1-3, wherein the antibody is in a pharmaceutical composition for subcutaneous administration comprising a solution comprising 6.7 mM L-histidine, 7.6% (w/v) sucrose, 0.004% (w/v) polysorbate 80, at pH 6.0.

6. The method of claim 4, wherein the antibody is administered intravenously to the subject at week 0 of the treatment, at a dosage of about 6.0 mg/kg body weight of the subject or 130 mg, 260 mg, 390 mg or 520 mg per administration.

7. The method of claim 6, wherein the antibody is further administered subcutaneously to the subject at week 8 of the treatment, at a dosage of about 90 mg per administration.

8. The method of claim 7, wherein the subject had previously failed or was intolerant of at least one therapy selected from the group consisting of an anti-TNF, vedolizumab, corticosteroids, azathioprine (AZA), and 6 mercaptopurine (6 MP), or the subject had demonstrated corticosteroid dependence.

9. The method of claim 7, wherein the antibody is administered in a maintenance dose every 8 weeks after the treatment at week 8 or every 12 weeks after the treatment at week 8.

10. The method of claim 9, wherein the subject is identified as having a clinical remission based on at least one of the global definition and the US definition by week 16 of the treatment and the clinical remission continues at least 44 weeks after week 0.

11. The method of claim 9, wherein the subject is in corticosteroid-free clinical remission at least 44 weeks after week 0.

12. The method of claim 9, wherein the subject is identified as having an endoscopic healing continuing at least 44 weeks after week 0.

13. The method of claim 9, wherein the subject is identified as achieving a clinical response based on the Mayo endoscopy subscore continuing at least 44 weeks after week 0.

14. The method of claim 9, wherein the subject is identified as having a mucosal healing continuing at least 44 weeks after week 0.

15. The method of claim 9, wherein the subject is identified as having a normalization of one or more biomarkers selected from the group consisting of C-reactive protein, fecal lactoferrin and fecal calprotectin continuing at least 44 weeks after week 0.

16. The method of claim 9, wherein the subject is in clinical response as determined by a decrease from baseline in the Mayo score by ≥30% and ≥3 points and a decrease from baseline in the rectal bleeding subscore ≥1 points or a rectal bleeding subscore of 0 or 1 continuing at least 44 weeks after week 0.

17. A method of treating moderately to severely active ulcerative colitis (UC) in a subject in need thereof, comprising:

a. intravenously administering to the subject an anti-IL-12/IL-23p40 antibody in a first pharmaceutical composition at a dosage of about 6.0 mg/kg body weight of the subject or 130 mg, 260 mg, 390 mg or 520 mg per administration at week 0 of the treatment, and

b. subcutaneously administering to the subject the anti-IL-12/IL-23p40 antibody in a second pharmaceutical composition at a dosage of 90 mg per administration at week 8 of the treatment,

wherein the antibody comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region comprising: a complementarity determining region heavy chain 1 (CDRH1) amino acid sequence of SEQ ID NO:1; a CDRH2 amino acid sequence of SEQ ID NO:2; and a CDRH3 amino acid sequence of SEQ ID NO:3; and the light chain variable region comprising: a complementarity determining region light chain 1 (CDRL1) amino acid sequence of SEQ ID NO:4; a CDRL2 amino acid sequence of SEQ ID NO:5; and a CDRL3 amino acid sequence of SEQ ID NO:6; and

wherein the subject is a responder to treatment by at least one measure of response to treatment selected from the group consisting of: (i) having a clinical remission based on at least one of the global definition of clinical remission with Mayo score ≤ 2 points with no individual subscore > 1 and the US definition of clinical remission with absolute stool number ≤ 3, rectal bleeding subscore of 0 and Mayo endoscopy subscore of 0 or 1, (ii) having an endoscopic healing with a Mayo endoscopy subscore of 0 or 1, (iii) achieving a clinical response based on the Mayo endoscopy subscore, (iv) having a mucosal healing, and (v) in clinical response as determined by a decrease from baseline in the Mayo score by ≥30% and ≥3 points and a decrease from baseline in the rectal bleeding subscore ≥1 points or a rectal bleeding subscore of 0 or 1, and

wherein the subject had previously failed or was intolerant of at least one therapy selected from the group consisting of: an anti-TNF, vedolizumab, corticosteroids, azathioprine (AZA), and 6 mercaptopurine (6 MP), or the subject had demonstrated corticosteroid dependence.

18. The method of claim 17, wherein the antibody comprises the heavy chain variable region of the amino acid sequence of SEQ ID NO:7 and the light chain variable region of the amino acid sequence of SEQ ID NO:8.

19. The method of claim 17, wherein the antibody comprises a heavy chain of the amino acid sequence of SEQ ID NO:10 and a light chain of the amino acid sequence of SEQ ID NO:11.

20. The method of any one of claims 17-19, wherein the first pharmaceutical composition further comprises a solution comprising 10 mM L-histidine, 8.5% (w/v) sucrose, 0.04% (w/v) polysorbate 80, 0.4 mg/mL L-methionine, and 20 μg/mL EDTA disodium salt, dehydrate, at pH 6.0.

21. The method of claim 20, wherein the second pharmaceutical composition further comprises a solution comprising 6.7 mM L-histidine, 7.6% (w/v) sucrose, 0.004% (w/v) polysorbate 80, at pH 6.0.

22. The method of any one of claims 17-19, wherein the subject is identified as having a clinical remission based on at least one of the global definition and the US definition by week 16 of the treatment.

23. The method of any one of claims 17-19, wherein the subject is identified as having an endoscopic healing by week 16 of the treatment.

24. The method of any one of claims 17-19, wherein the subject is identified as achieving a clinical response based on the Mayo endoscopy subscore by week 16 of the treatment.

25. The method of any one of claims 17-19, wherein the subject is identified as having a mucosal healing by week 16 of the treatment.

26. The method of any one of claims 17-19, wherein the subject is identified as having a normalization of one or more biomarkers selected from the group consisting of C-reactive protein, fecal lactoferrin and fecal calprotectin by week 16 of the treatment.

27. The method of any one of claims 17-19, wherein the subject is in clinical response as determined by a decrease from baseline in the Mayo score by ≥30% and ≥3 points and a decrease from baseline in the rectal bleeding subscore ≥1 points or a rectal bleeding subscore of 0 or 1 by week 16 of the treatment.

28. The method of any one of claims 17-19, wherein the subject is not a responder to the treatment with the antibody by week 8 and is a responder to the treatment by week 16 of the treatment.

29. A method of treating moderately to severely active ulcerative colitis (UC) in a subject in need thereof, comprising:

a. intravenously administering to the subject an anti-IL-12/IL-23p40 antibody in a first pharmaceutical composition at a dosage of about 6.0 mg/kg body weight of the subject or 130 mg, 260 mg, 390 mg or 520 mg per administration at week 0 of the treatment, and

b. subcutaneously administering to the subject the anti-IL-12/IL-23p40 antibody in a second pharmaceutical composition at a dosage of 90 mg per administration at week 8 of the treatment,

wherein the antibody comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region comprising: a complementarity determining region heavy chain 1 (CDRH1) amino acid sequence of SEQ ID NO:1; a CDRH2 amino acid sequence of SEQ ID NO:2; and a CDRH3 amino acid sequence of SEQ ID NO:3; and the light chain variable region comprising: a complementarity determining region light chain 1 (CDRL1) amino acid sequence of SEQ ID NO:4; a CDRL2 amino acid sequence of SEQ ID NO:5; and a CDRL3 amino acid sequence of SEQ ID NO:6, followed by a maintenance therapy,

wherein the maintenance therapy comprises subcutaneously administering to the subject the anti-IL-12/IL-23p40 antibody at a dosage of 90 mg per administration, once every 8 weeks or once every 12 weeks, and wherein the maintenance therapy is provided for 44 weeks and after treating with the antibody, the subject is a responder to treatment by at least one measure of response to treatment selected from the group consisting of: (i) having a clinical remission based on at least one of the global definition of clinical remission with Mayo score ≤ 2 points with no individual subscore > 1 and the US definition of clinical remission with absolute stool number ≤ 3, rectal bleeding subscore of 0 and Mayo endoscopy subscore of 0 or 1, (ii) having an endoscopic healing with a Mayo endoscopy subscore of 0 or 1, (iii) achieving a clinical response based on the Mayo endoscopy subscore, (iv) having a mucosal healing, and (v) in clinical response as determined by a decrease from baseline in the Mayo score by ≥30% and ≥3 points and a decrease from baseline in the rectal bleeding subscore ≥1 points or a rectal bleeding subscore of 0 or 1.

30. A method of treating moderately to severely active ulcerative colitis (UC) in a subject
in need thereof, comprising:

a. intravenously administering to the subject an anti-IL-12/IL-23p40 antibody comprising a heavy chain variable region of the amino acid sequence of SEQ ID NO:7 and a light chain variable region of the amino acid sequence of SEQ ID NO:8, in a first pharmaceutical composition at a dosage of about 6.0 mg/kg body weight of the subject or 130 mg, 260 mg, 390 mg or 520 mg per administration at week 0 of the treatment, and

b. subcutaneously administering to the subject the anti-IL-12/IL-23p40 antibody in a second pharmaceutical composition at a dosage of 90 mg per administration at week 8 of the treatment, followed by a maintenance therapy,

wherein the maintenance therapy comprises subcutaneously administering to the subject the anti-IL-12/IL-23p40 antibody at a dosage of 90 mg per administration, once every 8 weeks or once every 12 weeks, and after treating with the antibody, the subject is a responder to treatment by at least one measure of response to treatment selected from the group consisting of: (i) having a clinical remission based on at least one of the global definition of clinical remission with Mayo score ≤ 2 points with no individual subscore > 1 and the US definition of clinical remission with absolute stoolnumber ≤ 3, rectal bleeding subscore of 0 and Mayo endoscopy subscore of 0 or 1, (ii) having an endoscopic healing with a Mayo endoscopy subscore of 0 or 1, (iii) achieving a clinical response based on the Mayo endoscopy subscore, (iv) having a mucosal healing, (v) in clinical response as determined by a decrease from baseline in the Mayo score by ≥30% and ≥3 points and a decrease from baseline in the rectal bleeding subscore ≥1 points or a rectal bleeding subscore of 0 or 1.

Annex B:

Table reproduced from Professor Ciorba’s EIA at [75] showing medications approved by the FDA for treating either CD or UC, or both, before 24 September 2018.  The green cells indicate the FDA approval date for the relevant indication.  The yellow cells indicate that the drug was either in ongoing clinical trials or no clinical trials were conducted in relation to the relevant indication.  The red cells indicate a lack of safety and/or efficacy in the relevant indication.

Table reproduced from Professor Pavli’s EIR at [34] showing biologic medications approved by the TGA for the treatment of CD or UC, or both, before 24 September 2018.