eplaweplaw.org/.../2020/09/nl-vonnis-biogen-sb-v-richter-en.docx · web viewthe prefilled syringes...

JUDGMENT_______________________________________________________________

DISTRICT COURT OF THE HAGUE

Trade Team

Judgment of 29 July 2020

in the case with case number / docket number: C/09/581672 / HA ZA 19-1088 of

1. BIOGEN B.V.,having its registered office in Badhoevedorp, and

2. the legal person under foreign lawSAMSUNG BIOEPIS UK LIMITED,in Brentford, United Kingdom,

plaintiffs in the main action, defendants in the cross-action, counsel: mr. G. Kuipers in Amsterdam,

versus

the legal person under foreign lawRICHTER GEDEON NYRT,in Budapest, Hungary, defendant in the main action, plaintiff in the cross-action,counsel: mr. P. Marcelis in Amsterdam,

and in the case with case number / docket number C/09/584626 / HA ZA 19-1247 of

the legal person under foreign lawRICHTER GEDEON NYRT,in Budapest, Hungary, plaintiff in the main action, defendant in the cross-action,counsel: mr. P. Marcelis in Amsterdam, versus

1. BIOGEN NETHERLANDS B.V.,in Amsterdam and

2. SAMSUNG BIOEPIS NL B.V.,in Delft,

defendants in the main action, plaintiffs in the cross-action,

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C/09/581672 / HA ZA 19-1088 and C/09/584626 / HA ZA 19-124729 July 2020_______________________________________________________________________________

counsel: mr. G. Kuipers in Amsterdam.

The parties will be referred to below as Biogen et al. and Richter. Case 19-1088 will also be referred to as “the validity case”, while case 19-1247 will be referred to as “the infringement case”. The plaintiffs in the main action in the validity case will be referred to individually as B and SB and collectively as B/SB. The defendants in the main action in the validity case will be referred to individually as BNL and SBNL and collectively as BNL et al. The reference “Biogen et al.” refers to B/SB and BNL et al. collectively.

For Biogen et al., the cases were handled substantively by their above-mentioned lawyer and by mr. B.J. Berghuis van Woortman, A.F. Kupecz and E.W. Peijster, lawyers in Amsterdam. For Richter, the cases were handled substantively by their above-mentioned lawyer, together with mr. B.J. Mooij, lawyer in Amsterdam, and assisted by drs. K.M.L. Bijvank, patent attorney.

1. The proceedings

1.1. The course of the proceedings appears from:

in case 19-1088 (the validity case):

- the order of the Preliminary Relief Judge of this Court of 16 August 2019 in which B/SB was granted leave to issue a Writ of Summons against Richter under the VRO regime (accelerated proceedings on the merits in patent cases) (hereinafter: “VRO”);

- the Writ of Summons dated 27 August 2019;- the Motion for the Submission of Exhibits EP11-EP17 on behalf of B/SB;- the Statement of Defence/Statement of Claim in the Cross-Action, with Exhibits GP1-

GP11;- the Statement of Defence in the Cross-Action, with Exhibits EP18-EP23;- the Motion for the Submission of Further Exhibits on behalf of B/SB of 1 April 2020,

with Exhibits EP24 and EP25;- the Motion for the Submission of an Additional Exhibit on behalf of Richter of 1 April

2020, with Exhibit GP12;- the Motion for the Submission of a Further Exhibit on behalf of B/SB of 15 April 2020,

with Exhibit EP26;- the Motion for the Submission of Reactive Exhibits on behalf of Richter of 15 April

2020, with Exhibits GP l3 and GP14;- the Motion for the Submission of Reactive Exhibits on behalf of B/SB of 1 May 2020,

with Exhibits EP27-EP29;1 The Exhibits in the validity case are referred to with numbers, which are preceded by either “EP” (Exhibits originating from plaintiffs B/SB) or “GP” (Exhibits originating from defendant Richter).

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- the Motion for the Submission of a Reactive Exhibit on behalf of Richter of 1 May 2020, with Exhibit GP15;

- the Motion for the Submission of a Further Exhibit on behalf of B/SB of 13 May 2020, with Exhibit EP30;

and in case 19-1247 (the infringement case) from:

- the Order given by the Preliminary Relief Judge of this Court of 26 November 2019 in which Richter was granted leave to issue a Writ of Summons against BNL et al. in the accelerated proceedings on the merits in patent cases;

- the Writ of Summons dated 26 November 2019;- the Motion for the Submission of Exhibits RP21-RP10 on behalf of Richter;- the Statement of Defence/Statement of Claim in the Cross-Action, with Exhibits BP23-

BP39;- the Statement of Defence in the Cross-Action, with Exhibits RP11-RP15;- the Motion for the Submission of Further Exhibits on behalf of BNL et al. of 1 April

2020, with Exhibits BP40 and BP41;- the Motion for the Submission of Additional Exhibits on behalf of Richter of 15 April

2020, with Exhibits RP16 and RP17;- the Motion for the Submission of a Further Exhibit on behalf of BNL et al. of 15 April

2020, with Exhibit BP42;- the Motion for the Submission of a Reactive Exhibit on behalf of Richter of 1 May

2020, with Exhibit RP l8;- the Motion for the Submission of Reactive Exhibits on behalf of BNL et al. of l May

2020, with Exhibits BP43-BP45;- the Motion for the Submission of a Reactive Exhibit on behalf of Richter of 13 May

2020, with Exhibit RP19;- the Motion for the Submission of a Further Exhibit on behalf of BNL et al. of 13 May

2020, with Exhibit BP46;

and, furthermore, in both cases from:

- the letter from mr. Kuipers dated 22 May 2020 requesting the provision of an itemised overview of the litigation costs;

- the Motion for the Submission of an Overview of the Litigation Costs on behalf of Richter, which was received on 22 May 2020;

- the Additional Overview of the Litigation Costs on behalf of Richter, received on 26 May 2020;

2 In order to distinguish the Exhibits in the validity case from those in the infringement case, the Exhibits submitted by plaintiff Richter in the infringement case are referred to with the Exhibit number preceded by the letters “RP”, and the Exhibits submitted by the defendants BNL et al. are referred to with “BP” (followed by the Exhibit number).3 No Exhibit BP1 was submitted.

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- the email from mr. Kuipers dated 28 May 2020 with an additional Overview of the Litigation Costs;

- the pleading notes submitted in writing and exchanged between the parties on 27 May 2020 (see 1.3);

- the transposition tables for the Exhibits submitted in the validity and infringement proceedings (in the case of Biogen et al.: attached to their pleading notes; in the case of Richter: submitted with its email dated 28 May 2020).

1.2. By letter dated 15 May 2020, Biogen et al. objected to Exhibits of Richter and to the (new) contentions made therein by Richter, to which Richter reacted by email dated 19 May 2020. The objection, to the extent that it concerns Exhibits submitted in accordance with the relevant VRO regimes, was rejected by the District Court by letter dated 25 May 2020. In respect of the new contentions made in a number of these Exhibits, the District Court informed the parties in that same letter that it saw no reason at that stage to honour the objection of Biogen et al.

1.3. In connection with the coronavirus pandemic, the combined oral arguments, which had been scheduled in both cases in the corresponding VRO Orders for 29 May 2020, were held in adjusted form in consultation with the parties, without the physical presence of (counsel for) the parties. The combined pleading notes were exchanged between the parties in writing on 27 May 2020. The oral arguments in both cases were then “continued” during a video hearing on 29 May 2020, in the sense that the District Court posed questions to the parties and a Reply and Rejoinder were held.

1.4. Finally, 15 July 2020 was fixed as the date for judgment to be given.

2. The facts

2.1. Adalimumab is a monoclonal antibody against TNFa, a body-produced protein which is often involved in auto-immune diseases. The antibody adalimumab is the active ingredient of a medicinal product marketed by the pharmaceutical group AbbVie under the brand name “Humira®” in the Netherlands, among other countries, for the treatment of certain auto-immune diseases, including rheumatoid arthritis, Crohn’s disease and psoriasis. Humira was approved for Europe in September 2003 by the European Medicines Agency (EMA) and was covered, until October 2018, by AbbVie's (basic) patent for adalimumab, whose protection had been extended with an additional protection certificate and the paediatric extension. Humira is the best sold medicine in the world. It is administered through an injection.

2.2. In order to formulate adalimumab in an injectable solution, excipients are used for the stability of the antibody, including buffers. A buffer is an aqueous solution of two substances – a weak acid and the salt of the accompanying base, or vice versa, a base and the salt of the accompanying acid – which form a balance at a certain pH. Changes of

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the solution which would normally cause the pH to change will not do so, at least to a much smaller extent, if a buffer is present, because the balance between the buffer substances will change instead. The buffer used in Humira is a combination of citrate and phosphate.

2.3. Richter is holder of European patent EP 3 212 667 Bl (hereinafter: “the Patent” or EP 667), which is valid in the Netherlands, among other countries, for: 'Pharmaceutical anti-TNF-alpha Antibody Formulation’. The Patent was granted on 19 September 2018 on an application dated 28 October 2015 in which the priority of the Hungarian patent application HUP 1400510 dated 28 October 2014 was invoked.

2.4. EP 667 as granted has seven claims; only the first one is an independent claim. In the original English language, the claims read as follows:

1. A pharmaceutical formulation which is free of a phosphate buffer and selected from the group consisting of:

(a) a liquid aqueous pharmaceutical formulation comprising a therapeutically effective amount of Adalimumab in a buffered solution comprising L-Histidine and citrate, said formulation having a pH of 5 to 5.5 and having a content of aggregated species of Adalimumab after storage at 5°C for 3 to 6 months of less than 5 %;(b) a liquid aqueous pharmaceutical formulation comprising a therapeutically effective amount of Adalimumab in a buffered solution comprising L-Histidine and citrate, said formulation having a pH of 5 to 5.5 and having a content of aggregated species of Adalimumab after storage at 25°C for 3 to 6 months of less than 5 %;(c) a liquid aqueous pharmaceutical formulation comprising a therapeutically effective amount of Adalimumab in a buffered solution comprising L-Histidine and citrate, said formulation having a pH of 5 to 5.5 and having a content of acidic species of Adalimumab after storage at 25°C for 3 to 6 months of less than 40 %;(d) a liquid aqueous pharmaceutical formulation comprising a therapeutically effective amount of Adalimumab in a buffered solution comprising L-Histidine and citrate, said formulation having a pH of 5 to 5.5 and having a content of aggregated species of Adalimumab under heat stress conditions for 10 minutes at 55°C of less than 5 %;(e) a liquid aqueous pharmaceutical formulation comprising a therapeutically effective amount of Adalimumab in a buffered solution comprising L-Histidine and citrate, said formulation having a pH of 5 to 5.5 and having a content of acidic species of Adalimumab under heat stress conditions for 10 minutes at 55°C of less than 40%; and(f) a liquid aqueous pharmaceutical formulation comprising a therapeutically effective amount of Adalimumab in a buffer solution comprising L-Histidine and citrate, said formulation having a pH of 5 to 5.5 and retaining TNFa neutralizing activity of at least 80% after storage of 6 months at a temperature of 5°C or 25°C, and/or after being subjected to heat stress for 10 minutes at 55°C, freeze-thaw conditions at -20°C to 5°C.and/or mechanical stress;

wherein the concentration of Adalimumab in the pharmaceutical formulation of any one of (a) to (f) is 50 mg/mL and the formulation further comprising a polyol and a surfactant which is a polysorbate, and wherein the aggregated species are measured by Size Exclusion High Performance Liquid Chromatography (HP-SEC) and the acidic species are measured by Strong Cation Exchange (SCX) High Performance Liquid Chromatography (SCX-HPLC).

2. The formulation of claim 1, which further is suitable for single use subcutaneous injection and contained in a pharmaceutical container.

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3. A pharmaceutical container comprising the formulation of claim 1 or 2 wherein the container is a prefilled syringe, injection pen, ampoule, bottle, autoinjector or an infusion bag, preferably being closed under nitrogen protective atmosphere.

4. The container of claim 3, wherein the dose strength of Adalimumab is 40 mg.

5. The formulation of claim 1 or 2 or the container of claim 3 or 4 for use as a medicament for use in the treatment of a disorder in which TNFα activity is detrimental, preferably wherein the disorder in which TNFα activity is detrimental is selected from the group consisting of an autoimmune or inflammatory disorder.

6. The formulation or container for use in accordance with claim 5, wherein the formulation is designed to be administered subcutaneously to the human subject in need thereof on a biweekly dosing regimen of every 13-15 days.

7. The formulation or container for use in accordance with claim 5 or 6, wherein the formulation is to be administered in combination with an additional therapeutic agent that inhibits TNFα production or activity, preferably methotrexate.

2.5. The Dutch translation of the claims, which has not been challenged, reads as follows: [Dutch text of the claims].

2.6. The description of EP 667 includes the following section:

[0014] Indeed, hitherto combined aqueous buffer solutions including histidine and for example acetate or citrate have been discarded as not suitable or being inferior compared to histidine as the sole buffer component or in combination with others. For example, in international application WO2014/039903 at page 88 and 89 in Table H and HI among various others two formulations, formulation 6 and 10 of a proprietary Adalimumab biosimilar with histidine-acetate and histidine citrate are described in a short-term stability test for only one and two weeks and disregarded for further investigation of a pharmaceutical formulation. Rather, W02014/039903 teaches the avoidance of for example citrate but to use histidine only or in combination with a succinate buffer.Nevertheless, in one embodiment the pharmaceutical 5 formulation of the present invention does not consist of a formulation according to formulation 6 or 10 in Table H and H 1 at page 88 and 89 W)2014/039903.(...)[0024] As used herein the term "Adalimumab" refers to the fully human recombinant monoclonal lgGI antibody which binds to human TNF-alpha (hTNFα) and which is registered at Chemical Abstracts Service (CAS) under Registry Number 331731-18-1. (...)Adalimumab is marketed by Abbott Laboratories US (now AbbVie Inc US) as liquid pharmaceutical formulation for subcutaneous administration under the trade name HUMIRA®; see also international application W)2004/016286. Adalimumab was approved by the US Food and Drug Administration (FDA) in 2002 and by the European Medicines Agency (EMA) in 2003 for the treatment of rheumatoid. Since then it received additional approval for the treatment of other TNF-mediated chronic inflammatory diseases, including psoriatic arthritis, polyarticular juvenile idiopathic arthritis, psoriasis, plaque psoriasis, ankylosing spondylitis (AS), axial spondylarthritis, axial spondylarthritis without radiographic evidence of AS, Crohn's disease, pediatric Crohn's disease and ulcerative colitis. Adalimumab can be used alone or in combination with methotrexate (MTX) or other non-biological disease modifying anti-rheumatic drugs (DMARDs). For the treatment of rheumatoid diseases, Adalimumab is typically administered by subcutaneous injection at 40 mg every one or two weeks. It is supplied in glass vials, prefilled glass syringes and as an autoinjection device (HUMIRA® Pen), as a sterile, preservative-free solution for subcutaneous administration. The solution of HUMIRA® is clear and colorless with a pH of about 5.2. The prefilled syringes and autoinjector (Pen) comprise 40 mg of Adalimumab in 0.8 mL of a buffered solution of mannitol, citric acid monohydrate, sodium citrate,

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disodium phosphate dihydrate, monosodium phosphate dihydrate, sodium chloride and Polysorbate 80.[0025] Moreover, the term "Adalimumab" as used in the present invention encloses also proteins which are "biosimilar" to Adalimumab in accordance with the working definition declared in the published guidelines drafted by the FDA and the EMA which defines a biosimilar product to be one that is "highly similar" to a reference product despite minor differences in clinically inactive components (...) In practice there can be no clinically meaningful differences between the reference product and the biosimilar product in terms of safety, purity, and potency (...). In other words, a biosimilar form/protein of Adalimumab is an antibody which a regulatory authority deems to be "highly similar" to the reference product HUMIRA® on the basis of an abbreviated regulatory submission.(...)[0027] (...) In one embodiment, the route of administration, the dosage form, and/or the strength of the biosimilar Adalimumab protein of the present invention are the same as recommended in the Summary of Product Characteristics (SMPC) and Label information for HUMIRA® as approved by the EMA and FDA, respectively.

2.7. Biogen et al. are part of the Samsung Bioepis Group (hereinafter: “the SB Group”). The SB Group, to the extent relevant here, has developed and produced a biosimilar for adalimumab. This has resulted in an approved medicinal product which has been marketed in Europe, including the Netherlands, since October 2018 under the brand name “Imraldi®”. Imraldi does not contain a phosphate buffer.

2.8. SBNL is holder of the European market authorisation for Imraldi. In the Netherlands, BNL is the point of contact for Imraldi.

2.9. Biogen Inc (a member of the SB Group which is not party to these proceedings) and SB filed opposition against the Patent on19 June 2019. SBNL subsequently intervened in the opposition proceedings and is also considered as opponent.

2.10. In the opposition proceedings, Richter filed five auxiliary claims with the Opposition Department (hereinafter: “OD”) of the European Patent Office (hereinafter: “EPO”) on 18 November 2019 (I-V). In the present proceedings, auxiliary requests IV and V are relevant. The text of these auxiliary requests, which are available in English only, is set out below in 2.10.1 and 2.10.2. The sections that have been added, compared to the Patent, have been underlined there and sections that have been removed have been crossed out.

2.10.1. Auxiliary request IV reads as follows:

1. A p harmaceutical container for use as a medicament for use in the treatment of a disorder in which TNFα activity is detrimental. comprising a pharmaceutical formulation which is free of a phosphate buffer and selected from the group consisting of:(a) a liquid aqueous pharmaceutical formulation comprising a therapeutically effective amount of Adalimumab in a buffered solution comprising L-Histidine and citrate, said formulation having a pH of 5 to 5.5 and having a content of aggregated species of Adalimumab after storage at 5°C for 3 to 6 months of less than 5 %;

(b) a liquid aqueous pharmaceutical formulation comprising a therapeutically effective amount of Adalimumab in a buffered solution comprising L-Histidine and citrate, said formulation having a pH of 5

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to 5.5 and having a content of aggregated species of Adalimumab after storage at 25°C for 3 to 6 months of less than 5 %;(c) a liquid aqueous pharmaceutical formulation comprising a therapeutically effective amount of Adalimumab in a buffered solution comprising L-Histidine and citrate, said formulation having a pH of 5 to 5.5 and having a content of acidic species of Adalimumab after storage at 25°C for 3 to 6 months of less than 40 %;(d) a liquid aqueous pharmaceutical formulation comprising a therapeutically effective amount of Adalimumab in a buffered solution comprising L-Histidine and citrate, said formulation having a pH of 5 to 5.5 and having a content of aggregated species of Adalimumab under heat stress conditions for 10 minutes at 55°C of less than 5 %;(e) a liquid aqueous pharmaceutical formulation comprising a therapeutically effective amount of Adalimumab in a buffered solution comprising L-Histidine and citrate, said formulation having a pH of 5 to 5.5 and having a content of acidic species of Adalimumab under heat stress conditions for 10 minutes at 55°C of less than 40%; and(t) a liquid aqueous pharmaceutical formulation comprising a therapeutically effective amount of Adalimumab in a buffer solution comprising L-Histidine and citrate, said formulation having a pH of 5 to 5.5 and retaining TNFα neutralizing activity of at least 80% after storage of 6 months at a temperature of 5°C or 25°C, and/or after being subjected to heat stress for 10 minutes at 55°C, freeze-thaw conditions at -20°C to 5°C and/or mechanical stress;

wherein the concentration of Adalimumab in the pharmaceutical formulation of anyoneof (a) to (t) is 50 mg/ml, and the formulation further comprises a polyol and a surfactant which is a polysorbate, and wherein the aggregated species are measured by Size Exclusion High Performance Liquid Chromatography (HP-SEC) and the acidic species are measured by Strong Cation Exchange (SCX) High Performance Liquid Chromatography (SCX-H PLC); and wherein the formulation is suitable for single use subcutaneous injection and the container is a prefilled syringe or injection pen.

2. The formulation of claim I, which further is suitable for single use subcutaneous injection and contained in a pharmaceutical container.

3. 2. A The pharmaceutical container comprising the formulation for use in accordance with claim 1 or 2, wherein the container is a prefilled syringe, injection pen, ampoule, battle, autoinjector or an infusion bag, preferably being closed under nitrogen protective atmosphere.

4. 3. The container of for use in accordance with claim 1 or 2 3, wherein the dose strength of Adalimumab is 40 mg.

5. 4 The formulation of claim 1 or 2 or the container of for use in accordance with anyone of claims 1 to 3 or 4 for use as a medicament for use in the treatment of a disorder in which TNFa activity is detrimental, preferably wherein the disorder in which TNFα activity is detrimental is selected from the group consisting of an autoimmune or inflammatory disorder.

6. 5 The formulation or container for use in accordance with claim 5 4, wherein the formulation is designed to be administered subcutaneously to the human subject in need thereof on a biweekly dosing regimen of every 13-15 days.

7. 6 The formulation or container for use in accordance with claim 5 4 or 6 5, wherein the formulation is to be administered in combination with an additional therapeutic agent that inhibits TNFa production or activity, preferably methotrexate.

2.10.2. Claims 1-7 of auxiliary request V are identical to the claims of the Patent as granted; the only difference is the following disclaimer, which has been added at the end

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of claim 1:

: wherein the formulation does not consist of 50 mg Adalimumab in l0 mM Histidine and citrate, 65 mM mannitol. 100 mM NaCl and 0.1 % polysorbate 80

2.11. The international (PCT) patent application WO2014/039903 A2 “Stable Aqueous Formulations of Adalimumab” (hereinafter: “Manning”), published on 13 March 2014, includes the following section:

Field of the InventionThe present invention relates to aqueous pharmaceutical compositions suitable for long-term storage of adalimumab (including antibody proteins considered or intended as "biosimilar" or "bio-better" variants of commercially available adalimumab), methods of manufacture of the compositions, methods of their administration, and kits containing the same. (p. 1, lines 2-7)(...)In each of the five embodiments discussed above, (...) Preferably, adalimumab formulations containing the stabilizers mentioned above also do not contain buffer systems in which phosphate buffer and citrate buffer are present in combination, and, most preferably contains buffer systems free or substantially free of citrate buffer. In particularly preferred embodiments, (i) the optional additional stabilizer present in this embodiment is not sodium chloride, or comprises sodium chloride present in amounts not to exceed about 100 mM, and comprises at least one of arginine and glycine, including combinations of the two amino acids; (ii) the buffer, when present, contains no citrate, or at least no citrate and phosphate combination, but is instead at least one of histidine and succinate, including combinations thereof; and (iii) the stabilizer when it includes a polyol is preferably mannitol in amounts exceeding about 150 mM.In further embodiments the invention is directed to an aqueous, buffered pharmaceutical composition comprising adalimumab and a buffer, wherein (i) the composition is free or substantially free of a buffer combination that comprises both a citrate buffer and a phosphate buffer; and (ii) the composition exhibits long term stability. (p. 4, line 3 and lines 10-25)(...) .It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the invention, as claimed. Further representative embodiments are set forth in the numerous formulation studies reported in the detailed description, as well as the various embodiments listed in Appendices A, B and C attached hereto and made a part hereof. (p 8, lines 5-10)(...)BLOCK H FORMULATION STUDIESThe Block H formulations focused on three aspects of the adalimumab formulation: (l) higher protein concentrations, (2) formulations with no buffers present (other than the protein), and (3) the use of various buffer combinations beside citrate-phosphate (See Table H). (p. 87, lines 5-9)

TABLE HBLOCK H STUDY DESIGN

etc.

(page 884)

4 NB in this overview the protein concentrations of the adalimumab biosimilar in the third Colum are shown in mg/ml and the polysorbate concentration (PS80) in a % (see Table A, p.32). The other concentrations are stated in millimole per litre.

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TABLE H-1Measured pH for Block H formulations at t0, t1 (one week, 40 degrees C), and t2 (two weeks, 40 degrees C)

(etc.)

(page 89)

Methods of Treatment(...)Diseases or disorders that can be treated with the provided compositions include but are not limited to rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Wegener's disease (granulomatosis), Crohn's disease (or inflammatory bowel disease), chronic obstructive pulmonary disease (COPD), Hepatitis C, endometriosis, asthma, cachexia, psoriasis, and atopic dermatitis. (p. 111, lines 27-31)(...)The provided pharmaceutical compositions may be administered to a subject in need of treatment by injection systemically, such as by intravenous injection; (p. 112, lines 4-5)(...)In one embodiment, adalimumab is administered at 40mg by single subcutaneous (SC) injection; (p.113, lines 1-2)(...)The pharmaceutical compositions of this invention are particularly useful for parenteral administration, i.e., subcutaneously, intramuscularly, intravenously, (...) (p. 113, lines 27-28)(...) the pharmaceutical compositions of the present invention are suitable for administration using these new methods, e.g., Inject-ease®, Genject®, injector pens (...) (p. 114, lines 1-3)

The pharmaceutical compositions may, if desired, be presented in a vial, pack or dispenser device which may contain one or more unit dosage forms containing the 15 active ingredient. In one embodiment the dispenser device can comprise a syringe having a single dose of the liquid formulation ready for injection. The syringe can be accompanied by instructions for administration. In another embodiment, the present invention is directed to a kit or container, which contains an aqueous pharmaceutical composition of the invention. (p. 1 14, lines 13-19)(...)WHAT IS CLAIMED IS:l . An aqueous, buffered pharmaceutical composition comprising adalimumab and a buffer, wherein(i) the composition is free or substantially free of a buffer combination that comprises both a citrate buffer and a phosphate buffer; and (ii) the composition exhibits long term stability. (p. 147)(...)29. An aqueous, buffered pharmaceutical composition exhibiting long term stability, said composition comprising: (i) adalimumab; (ii) a buffer selected from the group consisting of histidine buffer, succinate buffer, and combinations thereof; (iii) a polysorbate or poloxamer surfactant, or combinations thereof; and (iv) one or both of the following:(a) a stabilizer selected from the group consisting of glycine, alanine, glutamate, arginine methionine, EDTA, sodium chloride, sodium sulphate, withal ions, and combinations thereof; and(b) a polyol selected from sorbitol, mannitol, and trehalose, or combinations thereof.30. The composition of claim 29 further comprising a buffer selected from the group consisting of phosphate, citrate, acetate, maleate and tartrate buffers, including combinations thereof. (p. 149)

2.12. The Prior Art Publishing No. PAPDEOTT002384, of A. Bender, with the title 'Alternative buffers for pharmaceutical anti-TNFa monoclonal antibody formulations' , published on 6 February 2013 (hereinafter: “Bender”) includes the following text, on the following pages:

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[third page, at the bottom:]

However, there is still the need for alternative or improved pharmaceutical formulations for antiTNFa antibodies. In the following further suitable liquid pharmaceutical formulation alternatives for anti-TNFa antibodies are designed.(...)

[on the fourth page:]

All suggested alternatives provide sufficient buffer capacities, show good long term stability, and have a good safety record.(...)The proposed alternative Adalimumab formulations are listed in the following. The preferred concentration ranges are disclosed within squared brackets.The alternative Adalimumab compositions are designed for formulation at a pH range between pH4.9 and pH 6.5 [pH 4.9 - pH 5.5] and comprise basically: 20-

130 mg/ml Adalimumab [45-55 mg/ml],1-10 mg/ml sodium chloride [6.0-6.4 mg/ml],2-25 mg/ml mannitol [10-14 mg/ml],0.1-5 mg/ml polysorbate 20 or 80 [0.5-2 mg/ml] and0.5-30 mM of the selected buffers 1) - 9).

The proposed buffers l ) - 9) as disclosed below, are prepared by mixing reasonable concentrations of conjugated acid and respective conjugated base to achieve the desired pH or alternatively by titrating the base (salt) with the free acid until the desired pH is reached. In production processes the buffer substances are added by weight and usually sodium hydroxide is applied for final pH adjustments.

(on the fifth page:]

(...)6) Citrate + Histidine• 1-10 mM Citric acid• 0.5-10 mM Trisodium citrate• 1-30 mM L-Histidine-HCI• 1-30 mM L-Histidine

(on the sixth page:]

(...)Remark: The mixed buffer systems 2) 3) 5) 6) and 8) require as minimum one basic component from one buffer and one acidic component from the other buffer. Not always all components as listed are necessary. See tables l and 2 for possible preparation and titration schemes for the proposed mono buffer solutions l ), 4 ), 7) and 9) and the proposed buffer combinations.

(and on the seventh page:]

Table 2: Possible preparation and titration scheme for combined buffer solutionsEtc.

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2.13. The oral hearings before the OD have been scheduled for 20 and 21 October 2020. The OD’s provisional opinion of 6 April 2020 that was sent to the parties states that the claims of the Patent are considered invalid for the time being inter alia because they lack novelty and inventiveness over Manning and Bender, among others. The Patent cannot be maintained in the amended form of the filed auxiliary requests either, according to the OD in its provisional opinion.

3. The dispute in case 19-1088 (the validity case)

In the main action

3.1. B/SB have claimed that the Court should invalidate the Dutch part of EP 667, while ordering Richter to pay all the litigation costs under Section 1019h DCCP5, increased by interest and the (post-judgment) costs, and, as far as the litigation costs are concerned, in a judgment that is enforceable notwithstanding appeal or opposition.

3.2. B/SB have based their claim on the fact that the Patent lacks novelty or inventive step over Manning, Bender and Humira, and that EP 667 fails to satisfy the enablement requirement.

3.3. Richter has raised a defence. In the case documents until the oral arguments, Richter had argued that and why EP 667 was valid in its view and, in case the District Court should find that claim 1 as granted was not novel over formulation 6 in Bender or formulation H-11 in Manning, Richter relied on (the validity of) the Patent in the form of auxiliary requests IV and V (also referred to below as “the Auxiliary Requests”) as fallback position. Richter’s argument that it would “restrict itself” to the Auxiliary Requests for the dispute in the Netherlands was presented by Richter for the first time in its pleading notes.

In the cross-action

3.4 Richter has claimed that the Court should hand a declaratory judgment stating that the products sold under the name “Imraldi®”, in any event products covered by the marketing authorisations mentioned in the Writ of Summons, come under the scope of protection of EP 667 and that B/SB should be ordered to pay the litigation costs under Section 1019h DCCP in a judgment that is enforceable notwithstanding appeal or opposition. The claimed declaratory statement concerns the Netherlands only.6

3.5 In its case documents until the oral arguments, Richter had argued that the Imraldi products mentioned in the claim infringed EP 667 as granted and conditionally relied on the Auxiliary Requests, contending that the Imraldi products were also covered by the scope of protection of the Auxiliary Requests. Richter’s argument that it would

5 Dutch Code of Civil Procedure.6 As Richter explained at the hearing.

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“restrict itself” to the Auxiliary Requests was presented by Richter for the first time in its pleading notes.

3.6. B/SB have raised a defence.

4. The dispute in case 19-1247 (the infringement case)

The main action

4.1. Richter has claimed – in summary - that the Court should prohibit BNL et al. from infringing EP 667 or from acting unlawfully (otherwise) in relation to Richter, and should order BNL et al. to compensate Richter for the damage suffered by Richter as a result of the infringement or as result of the unlawful conduct, or, at the option of Richter, to transfer the profits enjoyed by BNL et al., along with an ancillary claim (submission of a statement, recall, announcement, rendering of account), with the imposition of penalties, and to order BNL et al. to pay the full litigation costs under Section 1019h DCCP, increased by interest.

4.2. For the grounds of these claims, the Court refers to 3.5. In this case Richter submitted the Auxiliary Requests in its Statement of Defence in the Cross-Action. As it is BNL et al. who are selling the products under the naam “Imraldi®” or making the marketing authorisation available for this purpose, BNL et al. can be held liable, according to Richter, for the infringement or the unlawful conduct otherwise in relation to Richter.

4.3. BNL et al. have raised a defence.

The cross-action

4.4. BNL et al. have claimed that the Court should invalidate EP 667 and order Richter to pay the litigation costs under Section 1019h DCCP, including the post-judgment costs, with interest.

4.5. For the ground of this claim and the defence raised against it by Richter, the Court refers to paragraphs 3.2 and 3.3.

In the main action and the cross-action

4.6. The Court will further deal with the parties’ contentions below, to the extent they are relevant.

5. The assessment in both cases

The main action and the cross-action

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Jurisdiction

In case 19-1088 (the validity case)

5.1. The (unchallenged) international jurisdiction of the District Court to hear the claims in the main action follows from Article 24, opening sentence, and under 4 of the Brussels I Regulation (recast)7. That jurisdiction is limited to the Netherlands. The Court’s jurisdiction in the cross-action can be based on Article 8(3) of the Brussels I Regulation (recast). The relative jurisdiction follows from Article 80(1)(a) and (2)(a) DPA8.

In case 19-1247 (the infringement case )

5.2. In this case the international jurisdiction of the District Court (which has not been challenged either) to hear the claims in the main action follows from Article 4(1) of the Brussels I Regulation (recast), as the defendants are domiciled in the Netherlands. That jurisdiction also extends to the taking of cross-border measures. The Court’s international jurisdiction to hear the claim in the cross-action seeking to invalidate the Dutch part of EP 667 follows from Article 24, opening sentence, and under 4 of the Brussels I Regulation (recast). The relative jurisdiction of this Court is founded on Article 80(1)(a) and (2)(a) DPA.

5.3. As Richter confirmed at the hearing, the injunction prohibiting the infringement of the Patent as claimed by Richter is not limited to the Netherlands; Richter has also claimed an injunction prohibiting infringement in all the other countries where EP 667 is valid. The validity defence raised by BNL et al. in this case, however, also concerns the foreign parts of EP 667, for which courts other than the Dutch courts are exclusively competent to give a decision. So although the District Court is competent to judge the cross-border part of the claim seeking an injunction, it must await the findings of the exclusively competent foreign courts regarding the validity, if Richter requests a stay of

the proceedings and must dismiss the claim if no such request is made.9 Richter requested a stay of the proceedings (during the oral arguments), so the District Court is required to stay its judgment of the alleged involvement in a patent infringement of the foreign parts of EP 667 until the courts competent to do so abroad have decided on the validity of these parts.

Exhibits

7 Regulation (EU) No 1215/2012 of the European Parliament and of the Council of 12 December 2012 on jurisdiction and the recognition and enforcement of judgments in civil and commercial matters, entry into effect: 9-1-2013, Oj EU 2012, L 351/1 (the “Brussels I Regulation (recast)”).8 Dutch Patent Act 1995.9 Judgment of the Dutch Supreme Court, HR 30 November 2007, ECLI:NL:HR:2007:BA9608 (Roche/Primus II).

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5.4. The Court considers all the Exhibits submitted by the parties as having been submitted in both cases, even if an Exhibit was submitted in only one of the cases (as is evident from the transposition table submitted by Richter). All the parties are familiar with the Exhibits and no objection was voiced during the hearing to this decision of the Court.

Objection to contentions

5.5. By letter dated 25 May 2020, the Court informed the parties that it saw no reason at that stage to honour the objection of Biogen et al. of 15 May 2020 to new contentions in a number of Exhibits (the novelty of which contentions is challenged by Richter (see 1.2)). Because the contentions at issue play no part in the Court’s assessment, no further decision has to be taken on this matter.

The Patent

5.6. The Patent concerns a formulation for the antibody “adalimumab” without a phosphate buffer. As a result, it forms an alternative which is improved – as Richter has argued and Biogen et al. dispute - for the formulation in which Humira is marketed, which formulation does contain a phosphate buffer. The formulation claimed in EP 667 is defined in claim 1 of EP 667 with the following structural features:- a liquid aqueous pharmaceutical formulation,- comprising a therapeutically effective amount of Adalimumab in a concentration of

50 mg/ml,- in a buffer solution comprising L-Histidine and citrate, - which formulation has a pH of 5 to 5.5 and also comprises - a polyol and- a surfactant comprised of a polysorbate.The claim also explicitly says that the formulation must be free of a phosphate buffer.

5.7. The invention described in claim 1 is further defined on the basis of stability features enumerated in the claim under a)-f). It is not in dispute between the parties that the stability features are intrinsic to the structural features or that, if the structural features are satisfied, this entails that the stability features are also satisfied, and that the stability features therefore do not have any technical effect. Thus the stability features as such do not restrict the claim either.

5.8. Biogen et al. have contended with arguments, to the extent relevant here, that all the structural features of claim 1 have been clearly and unambiguously disclosed in two anticipations, viz. in Manning – a published international patent application - on page 88, formulation number 11 described in table H (hereinafter: “Manning H-11”) and in Bender – a scientific publication - formulation 6 (hereinafter: “Bender 6”) and that these features are therefore not novel. This has not been

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disputed by Richter as such; to counter this, Richter has merely argued that these formulations in Manning and Bender were not disclosed as pharmaceutical formulations, which claim 1 as granted would require. The question that arises, however, is whether the merits of that point in dispute still needs to be judged by the Court.

Fallback on Auxiliary Requests IV and V

5.9. At a (very) late stage of the proceedings, viz. in its pleading notes, Richter indicated that it would “restrict itself” for the Dutch proceedings to the Auxiliary Requests. According to Richter, all the arguments it has raised with regard to the Patent as granted apply a fortiori to the Auxiliary Requests, which place the same structural (and stability) features under protection as EP 667 as granted.10

5.10. During the hearing, Biogen et al. objected to Richter’s late change in strategy, in particular in the infringement case, because Richter had not (yet) relied in that case on the Auxiliary Requests in its Writ of Summons, which Richter should have done, according to Biogen et al. Richter was actually able to do so, because the Auxiliary Requests were filed with the EPO on 18 November 2019 and the Writ of Summons in the infringement case was issued subsequently, viz. on 24 November 2019, according to Biogen et al.

5.11. The objection of Biogen et al. to the effect that the Auxiliary Requests must be disregarded for the mere reason that they were submitted out of time is invalid. The fact that Richter could, theoretically, also have submitted the Auxiliary Requests in the infringement proceedings with its Writ of Summons does not mean that the Auxiliary Requests were submitted out of time. It is impossible to see how Biogen et al. have been harmed in their defence as a result of the time of submission, which applies even more so seeing that Biogen et al. were already familiar with these Auxiliary Requests. After the Auxiliary Requests had been filed with the EPO (simultaneously with auxiliary requests I-III, which are not relevant for the present proceedings) on 18 November 2019 (to which proceedings different legal persons of the SB Group are parties), Richter submitted them in these validity proceedings with its Statement of Defence (as Exhibit GP08) and in the infringement proceedings with its Statement of Defence in the Cross-Action (as Exhibit RP13). Biogen et al. were therefore familiar with the Auxiliary Requests and also considered them in their contentions and defences.

5.12. To the extent that the objection of Biogen et al. to the late change in strategy must be understood to mean that it concerns new contentions possibly made in and/or as a result of the fallback on the Auxiliary Requests during the oral arguments (either explicitly or implicitly), the following applies. In the Court’s view, Biogen et al. have not been harmed in their defence by the late amendment of the grounds of Richter’s

10 Richter’s pleading notes, paragraphs 5 and 44; in paragraph 44 Richter refers to the “main request”. The Court assumes that this refers to the Patent as granted.

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statement of claim, to the extent that Richter is not making any new contentions within that change of strategy. To the extent that Richter did make new contentions during the oral arguments in connection with the amendment of its statement of claim, this is different of course. Such contentions will be disregarded, in view of the principle of due process, as Biogen et al. were unable to react to such contentions, (even) during the first pleading session of the oral arguments.

The argument about the validity of the Dutch part EP 667 as granted has become irrelevant

5.13. The Court must now determine what legal consequences must be attached to the fact that Richter is no longer relying on the Dutch part of EP 667 (hereinafter also referred to as: “EP NL 667”) as granted in the present proceedings.

5.14. Biogen et al. have argued that the conclusion to be attached to that litigation strategy is that Richter has waived all its invalidity defences regarding EP NL 667 as granted, and that only the admissibility and validity of the Auxiliary Requests, to the extent that they deviate from the Patent as granted, must still be judged. According to Biogen et al., this already entails without any further substantive examination, as the District Court understands their argument, that EP NL 667 as granted must be considered to be invalid, so that the claim seeking its invalidation must be admitted.

5.15. During the hearing Richter clarified that the “restriction” had to be considered as a reduction of claim, in which Richter waived the Dutch part of the Patent in the form in which it was granted, which Richter could not do pending the proceedings, according to (the patent attorney of) Richter at the hearing, in view of Section 63(2) DPA, in any event not unilaterally, in the way set out in Section 63(1) DPA. However, that does not entail, according to Richter, that the Patent as granted can be invalidated, but that its validity must be judged in the form of the Auxiliary Requests, in which all the arguments that were presented with regard to the Patent as granted must be considered.

5.16. As Richter is no longer relying on the Patent as granted in the Netherlands, this can be equated, as Richter itself has also indicated, in terms of legal consequences – regardless of the merits of Richter’s argument that it cannot waive its right in the manner prescribed in Section 63(1) DPA - with a waiver of EP NL 667 as granted. In the Court’s view, this means that the debate about the Patent in the wider form in which it was granted has become irrelevant as a result of the fallback on the more limited Auxiliary Requests. After all, given that the validity of EP NL 667 as granted is no longer being defended by Richter, it must be held that the defences against the invalidity of that Patent are not maintained and that the condition Richter had originally attached to the fallback on the Auxiliary Requests in these proceedings has de facto been complied with.11

11 See the judgment of the Court of Appeal of The Hague of 5 June 2018 (High Point/KPN), ECLI:NL:GDHA:2018:1271.

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5.17. The above entails that the Court will assume in the following that claim 1 of EP NL 667 is not novel over formulations Bender 6 and Manning H-11. Richter’s defence that these formulations are not 'pharmaceutical formulations’ and the debate about whether the Patent and the anticipations are or are not an improvement compared to (the formulation of) Humira, regardless of their merits, are not relevant anymore. Any other finding would mean that the fallback on the more limited Auxiliary Requests would in fact be meaningless.

5.18. As opposed to what Biogen et al. wish to convince the Court of, this, however, does not mean that the claim seeking the invalidation of EP NL 667 can be admitted as a result of the fallback on the Auxiliary Requests. Although the defences raised against the invalidity of claim 1 of the Patent as granted, admittedly, no longer have to be judged, the Court must determine, before being able to decide on the invalidity, whether EP NL 667 as it reads according to the Auxiliary Requests (which are apparently intended to repair the lack-of-novelty objection to the formulation claimed in claim 1 of EP 667 as granted) can mean that the Patent can be maintained in the more limited form(s) proposed therein.

The judgment of claim 1 of EP 667 according to Auxiliary Request IV

5.19. Claim l of this Auxiliary Request (see 2.10.1) is, according to Richter, a combination of granted claims 1, 2, 3 and 5. The relevant part of claim 1 of this Auxiliary Request is set out again below:

1. A pharmaceutical container for use as a medicament for use in the treatment of a disorder in which TNFa activity is detrimental, comprising a pharmaceutical formulation which is free of a phosphate buffer and selected from the group consisting of:(...)

; and wherein the formulation is suitable for single use subcutaneous injection and the container is a prefilled syringe or injection pen.

5.20. Claim I seems to be formulated here as a pseudo second medical-use claim within the meaning of Article 54(5) EPC12 (Section 4(6) DPA), as the subject of the claim is not a substance or mixture ; the subject of protection is “a pharmaceutical container for use as a medicament for the treatment of ( ...)”, in which the container contains adalimumab according to the formulation claimed in claim l of the Patent as granted and can be a “prefilled syringe” or an “injection pen”.

5.21. Apart from the question whether this Auxiliary Request satisfies the requirement of clear claims of Article 84 EPC (Biogen et al. have pointed out that the text suggests that the container itself is presented as a medicinal product, while this formulation, as opposed to what Richter has argued, is not disclosed in the application), the combination of a known formulation with a “prefilled syringe” or an “injection pen” does not make what is claimed novel. The starting-point for a novelty assessment is that

12 Convention on the Grant of European Patents (European Patent Convention).

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a measure is not novel, if all its features are explicitly or implicitly disclosed in a direct and unambiguous manner to an average skilled person, who uses his common general knowledge, in one or two prior-art sources. In this assessment, the content of the prior-art document as a whole must be considered. If different embodiments are found in one document and the novelty plea concerns a combination of different elements of these embodiments, the criterion of the test to be applied is whether the document includes a “clear teaching combining them”.13

5.22. As considered above, it is no longer in debate that the claimed formulation represented the prior art on the priority date. To the extent that the use of a known formulation in a container claimed in claim l of Auxiliary Request IV was not already implicitly disclosed in that way, given the common general knowledge of the relevant skilled person about the manner of administration of Humira, among other products (as set out in [0024] of the description of EP 667, see 2.6), Manning also clearly and unambiguously disclosed the combination of the pharmaceutical formulations disclosed therein with a method of administration as referred to in Auxiliary Request IV. After all, pages 113 and 114 of that anticipation explicitly teach the skilled person that “the pharmaceutical compositions of this invention” can be administered subcutaneously, for instance with an injection pen or “a syringe having a single dose of the liquid formulation ready for injection” (see 2.11). Manning H-11 can be considered as a “pharmaceutical composition of this invention” for the mere reason that this formulation is claimed in Manning (in claims 1 and 30, in combination with 29, see 2.11) and is therefore part of the “formulations of the invention” referred to and disclosed in Manning. The combination of this formulation Manning H-11 (as well) with a container (syringe or injection pen) for its administration is thereby clearly and unambiguously disclosed. As opposed to what Richter has argued, there is no impermissible combination of different embodiments. After all, Manning actually teaches that all the embodiments, including formulation Manning H-11, can be used in the manner set out above.

5.23. As a result, the curtain falls for claim l of Auxiliary Request IV. For the sake of completeness, the Court observes that it is impossible to see why the inclusion of a known formulation in a known container would constitute an inventive step.

5.24. Richter has also argued that Manning’s theory actually teaches away from formulation H-11, which formulation is allegedly merely a “reference formulation” which was included for comparative purposes only. Therefore that formulation, according to Richter, does not come under the scope of the invention disclosed in Manning and therefore, as the Court understands in connection with Auxiliary Request IV, it cannot be a disclosure that destroys the novelty of the combination of that formulation with a method of administration/container. Apart from the fact that Richter has actually already

13 Case Law of the Boards of Appeal of the European Patent Office (2016), p. 104, with a reference to inter alia T 1988/07, ECLl:EP:BA:2010:Tl98807.20101008.

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given up this argument by falling back on the Auxiliary Requests and that it is also not possible to see why a “reference formulation” containing all the structural features of the claimed formulation could not be novelty-destroying, the Court will ignore this defence, because Manning provides no factual basis for this argument. In support of its argument, Richter has referred to a section on page 4, lines 17-19, where Manning teaches that the buffer, if present, may not comprise citrate or in any event a combination of citrate and phosphate. That section, however, only relates to a number of embodiments, while the section immediately underneath it describes a different embodiment in which only the citrate/phosphate combination is excluded as a buffer. In the claims of Manning referred to in the previous paragraph of this judgment, formulations are therefore claimed wherein a citrate buffer is used in combination with a histidine buffer, as disclosed in Manning H-11.

5.25. In the opinion of the Court, Claim 1 of EP NL 667 is therefore also not valid in the proposed amended form of Auxiliary Request IV.

The assessment of claim 1 of EP 667 according to Auxiliary Request V

5.26. In this Auxiliary Request a disclaimer has been added to claim 1 of the Patent in order to exclude Manning H-11 (see 2.10.2). For the sake of convenience, this disclaimer is repeated below:"wherein the formulation does not consist of 50 mg Adalimumab in 10 mM Histidine and citrate, 65 mM mannitol, 100 mM NaCl and 0.1 % polysorbate 80"

5.27. In order to meet an objection of Biogen et al. regarding the lack of clarity (Article 84 EPO), Richter has relied in the alternative on a particularised Auxiliary Request V, which reads as follows:"wherein the formulation does not consist of 50 mg Adalimumab in 10 mM Histidine and 10 mM citrate, 65 mM mannitol, 100 mM NaCl and 0.1% polysorbate 80"

[underlining added by the Court in order to highlight the difference with the earlier text of Auxiliary Request V]

5.28. For the basis of the included disclaimer, Richter has referred to [0014] of the description of EP 667 (see 2.6), which section corresponds literally with a section in the application as filed (on page 14, last paragraph and page15, last paragraph). In that section, formulation 10 from table H of Manning must be read as formulation 11 (which describes a histidine/citrate buffer), according to Richter.

5.29. Even if it is assumed that the text of the Auxiliary Request is formally permitted (also because the mentioned section in the application offers sufficient basis for the exclusion and there is no added matter within the meaning of Article 123(2) EPO, as Biogen et al. have argued, and the Auxiliary Request also satisfies the requirements of Article 84 EPO), the Court finds that this Auxiliary Request cannot save the Patent. The

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reason for this is as follows.

5.30. The starting-point in the Court’s assessment, in view of Richter’s fallback on the Auxiliary Requests, is that Bender 6 is novelty-destroying for claim 1 of the Patent as granted (see ground 5.17). Richter’s argument at the hearing that Bender cannot be novelty-destroying for Auxiliary Request V, because the formulation in that document was not disclosed as a pharmaceutical formulation (an argument Richter had also raised with regard to the Patent as granted), is therefore a lost cause.

5.31. Formulation Bender 6 is a wider anticipation than Manning H-11. Bender 6, for instance, discloses a formulation with a buffer concentration in a range, while Manning H-11 only discloses specific buffer concentrations of 10 mM. Bender 6 also discloses polysorbate and mannitol (a polyol) concentrations across a range, while Manning H-11 only relates to 65 mM mannitol and 0.1% polysorbate 80.

5.32. As the disclaimer only concerns the specific concentrations mentioned in Manning H-11, formulation Bender 6 partly falls outside that exclusion. Claim 1 (also in the way it reads according to Auxiliary Request V) does not include a restriction for the polyol and polysorbate concentrations, so the wider disclosures of Bender 6 also come under the scope of that claim. Moreover, claim 1 does not restrict the concentration of the L-Histidine and citrate buffers, except that the result must have a pH value of 5 to 5.5. The preferred pH range of the formulations disclosed in Bender (4.9 to 5.5) thus corresponds with this to an important degree.

5.33. Therefore novelty-destroying formulation Bender 6 is not excluded, in any event it is only partly excluded, by the inclusion of a disclaimer relating to Manning H-11. To the extent that Bender 6 falls outside the disclaimer and falls within the claimed scope of protection of EP 667, this anticipation therefore continues to be novelty-destroying, so that the Patent cannot be maintained in the amended form of Auxiliary Request V either.

5.34. This means that in the Court’s view, claim 1 of EP NL 667 is not valid in the proposed amended form of Auxiliary Request V.

Dependent claims

5.35. For the other claims of the Auxiliary Requests that depend on claim 1, the Court observes that Richter has not defended the amended dependent claims 2-5 of Auxiliary Request IV, while Biogen et al. have argued that they are invalid. It has not been contended or appeared to the Court that these dependent claims make the Patent valid. Dependent claims 2-6 of Auxiliary Request V are identical to those of the Patent as granted. Although Richter has argued that claims 3, 4 and 6 of that Auxiliary Request are novel over Bender, because Bender does not disclose the specific pharmaceutical

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containers claimed therein, Richter has failed to clarify why the containers claimed in these dependent claims, which must be deemed to represent common general knowledge of the skilled person, can make what is claimed in claim 1 novel, so these claims will also be invalidated. In any event that application lacks inventive step. As for dependent claim 7 of Auxiliary Request V (which corresponds with claim 7 of the Patent as granted and with claim 6 of Auxiliary Request IV), Richter has not raised any defence against the contention of Biogen et al. that the administration of adalimumab (or an adalimumab formulation) in combination with methotrexate represents common general knowledge (as also set out in paragraph [0024] of the description of the Patent, see 2.6), so this dependent claim is deemed to be invalid as well.

Unlawful conduct?

In case 19-1247 (infringement case)

5.36. In the infringement case, Richter has based its claims against SBNL on unlawful conduct in the form of making available the marketing authorisation (for Imraldi) to BNL in order to sell Imraldi in the Netherlands, and to other entities in Europe in order to sell Imraldi in other European countries.

As the Dutch part of the Patent is found to be invalid, there can be no question of unlawful conduct in the Netherlands as contended by Richter either. The ground of the unlawful conduct in other countries has not been substantiated by Richter, apart from the alleged (indirectly) infringing conduct in other countries for which the judgment has been stayed, so the Court will disregard this, also in view of the rebuttal by BNL et al.

Final conclusion

In case 19-1088 (validity case)

5.37. The foregoing leads the Court to finally conclude that EP NL 667 as granted is invalid, also in the form of the proposed Auxiliary Requests, so the claim seeking the invalidation of the Dutch part of the Patent in the validity case will be admitted. This entails that the declaratory judgment sought in the cross-action will be refused.

In case 19-1247 (infringement case)

5.38. Richter’s claims in the infringement case, to the extent that they concern the infringement of the Dutch part of EP 667, will be dismissed, as it is not possible to infringe an invalid patent. The other contentions and defences, including the prior use relied on by BNL et al., do not need to be discussed.

5.39. To the extent that the claims concern a (direct or indirect) infringement of other

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national parts of EP 667, their judgment depends on the opinion about the validity of these national parts, and Biogen et al. have pleaded that they are invalid. As already considered within the scope of the Court’s jurisdiction (see 5.3), the Court will stay its decision on this part of the claims, until the invalidity has been decided on in the jurisdictions concerned. The case will be referred to the parking docket, on the understanding that the party first ready to act can arrange for the case to be placed on the docket again in order to continue litigation about this part of the claims, as soon as it has been established whether EP 667 is valid in the countries concerned.

5.40. The claim in the cross-action brought by BNL et al. in the infringement case will be dismissed, given the outcome in the validity case, due to lack of interest. A patent cannot be invalidated twice.

Litigation costs

5.41. In the invalidity case, Richter will be ordered to pay the litigation costs in the main action and in the cross-action as the party against whom judgment was for the most part given. In the infringement case, Richter will be ordered to pay the costs in the main action. In the cross-action in the infringement case, BNL et al. must pay Richter’s costs; these costs, however, are fixed at nil, because this is a repetition of moves in Richter’s invalidity defence in the validity case.

5.42. Biogen et al. have claimed that the litigation costs should be compensated in full. These costs have been itemised by Biogen et al. and amount to approx. one million euros, including disbursements and fees of three law-firms. Richter, which has presented litigation costs totalling € 323,605.01 itself, has objected to the level of the costs presented by Biogen et al. and has contended they are excessive and in any event not reasonable and proportionate. Richter has claimed that any cost award to be given against it should be reduced to the costs presented by Richter itself, or to a maximum of € 400,000.

5.43. The Court is of the opinion that the costs presented by Biogen et al., also allowing for that fact that B/SB and BNL et al. have always acted jointly in both cases and also submitted an itemisation not broken down per party, are not reasonable and proportionate in cases such as the present one, where the contentions regarding the invalidity and infringement for the most part correspond with each other in both cases. Therefore, the total litigation costs of Biogen et al. that Richter will be ordered to pay are capped at € 400,000, which amount is considered fair and proportionate by the Court. The litigation costs will be equally divided between the two cases. In the validity case € 50,000 (one quarter of the total amount) will be allocated to the defence raised in the cross-action. All the costs and disbursements will be deemed included in the amounts thus fixed. The claimed statutory interest on the litigation costs will be awarded as being undisputed, but only with effect from the date lying 14 days after the service of this

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judgment.

5.44. There is no reason for awarding the post-judgment costs as claimed in the validity case, as the cost award also constitutes an enforceable title for these post-judgment costs.14

6. The decision

The District Court:

in case 19-1088 (the validity case)

in the main action

6.1. invalidates the Dutch part of EP 3 212 667 B1;

6.2. orders Richter to pay the litigation costs estimated on the side of B/SB until today’s date at € 150,000, to be increased by the statutory interest on that amount, calculated in respect of the period from the fifteenth day after the service of this judgment until the day of full payment;

in the cross-action

6.3. dismisses the claims;

6.4. orders Richter to pay the litigation costs estimated on the side of B/SB at € 50.000 until today’s date;

in case 19-1247 (the infringement case)

in the main action

6.5. denies the claims save as provided in 6.6;

6.6. defers the decision on the claims to the extent that they concern the foreign parts of EP 667 referred to in ground 5.39;

6.7. decides that the party first ready to act can arrange for the case to be placed on the docket after the time further described in ground 5.39, last sentence;

14 Judgment of the Dutch Supreme Court HR 19 March 2010, ECLI:NL:HR:2010: BL1116.

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6.8. orders Richter to pay the litigation costs estimated on the side of BNL et al. until today’s date at € 200,000, to be increased by the statutory interest thereon, calculated in respect of the period from the fifteenth day after the service of this judgment until the day of full payment;

In the cross-action

6.9. dismisses the claims;

6.10. orders BNL et al. to pay the litigation costs estimated on the side of Richter at nil;

in both cases in the main action and the cross-action

6.11. declares that the cost awards are enforceable notwithstanding appeal or opposition.

This judgment was given by mr. M.E. Kokke, mr. M. Knijff and mr. C. Schüller and was pronounced in public by mr. D. Nobel, docket judge, on 29 July 2020.

eplaweplaw.org/.../2020/09/nl-vonnis-biogen-sb-v-richter-en.docx · web viewthe prefilled syringes...

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