Litigation Updates

There were few important judgments published fortnight while I was on hiatus. Now I am back & will provide the summary of those judgments in due course of time. But for time being here are those in case you missed. Keep reading!!

Asenapine - USA

On Nov 15, 2018, Delaware court found Sigmapharma’s ANDA infringes claim 1 of U.S. Patent No. 5,763,476 which covers Saphris®. Court held that Sigmapharm’s accused product disintegrates within 30 seconds in water at 37°C. Forest has proven that 6/6 tablets disintegrated within 30 seconds for at least one run each from representative batches.

Naproxen & Esomeprazole - USA

On Nov 19, 2018, New Jersey court found claims covering Vimovo® invalid as indefinite in summary judgment proceeding. Court held that claims of U.S. Patent Nos. 9,220,698 and 9,393,208 are indefinite because of the claim term ‘target’. Specifically it is not possible to comprehend what these phrases mean, because pills cannot be said to set goals or have targets.

Buprenorphine & Naloxone (Suboxone®) - USA

On Nov 20, 2018, Federal Circuit vacated preliminary injunction granted by district court which was on erroneous interpretation of claim scope of US 9,931,305. Court held that the ’305 claims are patentably indistinct from the ’514 claims (decided previously) and that claim preclusion is likely to apply. As a result, Indivior has not shown that it is likely to succeed on the merits of its infringement claim against Dr Reddy’s.

Methylphenidate (Quillivant XR®) – USA

On Nov 20, 2018, Federal Circuit vacated invalidity decision of Delaware court as it was based on inadequate fact-findings. Patents-in-suit were U.S. Patent Nos. 8,465,765 (’765 patent), 8,563,033 (’033 patent), 8,778,390 (’390 patent), 8,956,649 (’649 patent), and 9,040,083 (’083 patent).

Fulvestrant – Netherlands

On Nov 27, 2018, The Court of Appeal confirmed the validity of AstraZeneca’s patent and vacated the first instance decision.

Pregabalin - UK

On Nov 14, 2018, UK Supreme Court in a landmark judgment in Warner-Lambert v Generics (UK) (Mylan) case found Lyrica® pain patent invalid & not infringed by generic filers.

This appeal to UKSC raises the question of how the concepts of sufficiency and infringement are to be applied to a “Swiss-form patent” relating to a specified medical use of a known pharmaceutical compound. Herein below providing the summary given by court in understanding the decision. The full judgment of the Court is available at: http://supremecourt.uk/decided-cases/index.html.

The Appellant (“Warner-Lambert”/ Pfizer) is the proprietor of European Patent No. 0641330 for Isobutylgaba. This is used for the treatment of seizure disorders, including epilepsy. Pregabalin, a derivative compound of Isobutylgaba, is marketed by Warner-Lambert under the “Lyrica®” brand. Patent No. 0641330 expired on 17 May 2013. This appeal concerns a second European Patent No. EP(UK) 0934061 entitled “Isobutylgaba and its derivatives for the treatment of pain”. The claims of the Patent (which define the scope of the patent protection) are all purpose limited. Most relevant are Claims 1-3 on the use of pregabalin for treating (1) pain, (2) inflammatory pain and (3) neuropathic pain. Lyrica has marketing authorisation in the EU for treatment of peripheral and central neuropathic pain, epilepsy and generalised anxiety disorder. It is one of Pfizer’s most successful drugs in the UK. The First Respondent (“Mylan”) and the Second Respondent, Actavis Group PTC EHF (“Actavis”), are pharmaceutical companies mainly engaged in marketing generic pharmaceutical products. 

Actavis markets a generic pregabalin product under the brand name “Lecaent”, launched in 2015. In these proceedings, Mylan and Actavis claimed the revocation of the Patent on the grounds of lack of inventive step and insufficiency. Warner-Lambert claims that Actavis infringes Claims 1 and 3 above.

At first instance, Arnold J rejected the arguments based on lack of inventive step. These are no longer in issue. Further, he held that Claim 1 (pain) and Claim 3 (neuropathic pain) were invalid because he construed Claim 1 as extending to all pain and Claim 3 as extending to all neuropathic pain. He found that there was sufficient disclosure in the specification to support the claim that pregabalin was efficacious in the treatment of inflammatory and peripheral neuropathic pain, but not central neuropathic pain. Both claims therefore failed for insufficiency. The result of the judge’s decision was to remove patent protection for the manufacture of pregabalin for the treatment of both peripheral and central neuropathic pain. Arnold J also rejected as an abuse of process an application concerning an amendment to narrow the Patent.

The Court of Appeal (Floyd, Kitchin and Patten LJJ) upheld the judge’s findings, and his decision on the amendment application. The judge and Court of Appeal differed in their approach to infringement in patent cases confined to manufacture for a particular use.

On appeal to the Supreme Court, Warner-Lambert contended that all the claims of the Patent were valid. Their main aim is to establish the validity of their claims relating to neuropathic pain or, at least, peripheral neuropathic pain. Actavis and Mylan cross-appealed, arguing that none of the claims as to neuropathic pain are valid. They only accept as valid the claims limited to inflammatory pain, for which there is no marketing authorization. This gives rise to four issues on appeal: (i) the construction of the claims (in particular, Claim 3 as to neuropathic pain); (ii) amendment and abuse of process; (iii) the sufficiency of the disclosure in the specification; and (iv) the test for infringement of a patent in relation to manufacturing for a limited use.

The Supreme Court unanimously affirmed issues i & ii: (1) the view of both courts that Claim 1 extends to all pain and Claim 3 to all neuropathic pain, whether peripheral or central, and (2) Arnold J’s decision rejecting Warner-Lambert’s application to amend the Patent to narrow it.

Issue (iii) – Sufficiency of disclosure in specification for Claims 1 and 3:

The court holds, by a majority that the disclosure in the specification supports the claims in relation to inflammatory pain, but not neuropathic pain, whether peripheral or central. Claims 1 and 3 therefore fail for insufficiency. Thus, the appeal is dismissed and the cross-appeal allowed. The majority’s approach requires the patentee to demonstrate that the specification discloses some scientific reason why the implied assertion of efficacy in the patent claim may well be true. More than a bare assertion or mere possibility of therapeutic efficiency is required, though a priori reasoning (not necessarily only experimental data) may suffice. This respects the principle that the patentee cannot claim a monopoly of new use for an existing compound without real disclosure. Lord Hodge (dissenting) proposes an alternative approach to sufficiency, preferring a lower standard of plausibility, and would have dismissed the cross-appeal. Lord Mance agrees with Lord Hodge on this issue, concluding that the majority’s approach imposes too high a threshold.

Issue (iv) – Correct test for infringement of patent manufactured for a limited use:

The court unanimously holds that if Claims 1 and 3 had been valid, they would not have been infringed by Actavis. The reasons for arriving at this agreed result differ substantially. Lord Sumption and Lord Reed consider that the intention of the alleged infringer, whether subjective or objective, is irrelevant and that the sole criterion of infringement is whether the product as it emerges from the manufacturing process, including any labelling or accompanying leaflet, is presented as suitable for the uses which enjoy patent protection – the “outward presentation” test. On the facts of this case, it is not disputed that “Lecaent” was sold with labels and patient information to the effect that it was for the treatment of seizure disorders and general anxiety disorder. Lord Mance agrees that the test depends on the objective appearance and characteristics of the product as it is prepared, presented and put on the market, but considers that in rare cases the context may make it obvious that these are not to be taken at face value. Lord Briggs and Lord Hodge prefer the view of Arnold J that the test is whether the alleged infringer subjectively intended to target the patent-protected market (Arnold J found they had not so intended).

Cyclosporine – USA

On Nov. 13, 2018, Federal Circuit affirmed (Rule 36 judgment) Texas judge’s decision that patents covering Allergan’s Restasis® are invalid.

Previously, on Oct. 16, 2017, Judge Bryson of Eastern District of Texas issued an opinion & found patents [U.S. Patent Nos. 8,629,111; 8,633,162; 8,642,556; 8,648,048; 8,685,930 and 9,248,191] invalid as obvious (reported here on this blog).  In short, the obviousness dispute in this case centered on Allergan’s assertion that the Restasis formulation exhibited unexpected results compared to the prior art. Allergan stated that the prior art patent discloses ranges of amounts of cyclosporin (0.05% to 0.40%) and castor oil (0.625% to 5.0%) that cover Restasis. Allergan argued however, that the particular combination in Restasis of 0.05% cyclosporin and 1.25% castor oil is a critical value that produces unexpected results far better than would be expected for the range of values disclosed in prior arts. For that reason, Allergan contended that the critical value of 0.05% cyclosporin with 1.25% castor oil is patentable, even though it falls within the ranges disclosed and claimed in prior art patent. Court, however, found that a person of skill reviewing prior arts & the underlying Phase 2 data, would not conclude that the 0.1% cyclosporine /1.25% castor oil formulation was more effective than the 0.05% cyclosporin/0.625% castor oil formulation. A person of skill reviewing those papers would come to the conclusion that neither formulation was more effective than the other in Phase 2. That person of skill would reach the same conclusion for Phase 3. The court finally held that based on the extensive amount of pertinent prior art, Allergan is not entitled to renewed patent rights for Restasis in the form of a second wave of patent protection. The Court therefore held that while Allergan has proved by a preponderance of the evidence that the defendants have infringed the asserted claims of the Restasis patents, the defendants have proved by clear and convincing evidence that the asserted claims of the Restasis patents are invalid for obviousness.

Rituximab - USA

Decision on IPR: Nov 08, 2018

AIA Review	Filing Date	Institution Date	Petitioner	US Patent	Respondent	Status
IPR2018-00186	12/01/2017	06/14/2018	Pfizer, Inc.	9,296,821	Biogen Inc.	Terminated

On US’821 patent, Celltrion previously filed IPR (IPR2017-01095) in which Board on Oct 04, 2018 issued final written decision & found claims 1-6 unpatentable.

US 9,296,821 (Biogen Inc; Exp: Jun 11, 2019) – Non OB

1. A method for treating low grade or follicular non-Hodgkin's lymphoma (NHL) comprising administering to a patient a therapeutically effective amount of rituximab during a chemotherapeutic regimen, wherein the chemotherapeutic regimen consists of cyclophosphamide, vincristine, and prednisone (CVP therapy), wherein the method comprises administering 375 mg/m² of rituximab, and wherein the method provides a beneficial synergistic effect in the patient.

2. A method for treating low grade or follicular non-Hodgkin's lymphoma (NHL) comprising administering to a patient 375 mg/m² of C2B8 during a chemotherapeutic regimen consisting of cyclophosphamide, vincristine, and prednisone (CVP therapy).

3. A method for treating low grade or follicular non-Hodgkin's lymphoma (NHL) comprising administering to a patient 375 mg/m² of a chimeric anti-CD20 antibody during a chemotherapeutic regimen consisting of cyclophosphamide, vincristine, and prednisone (CVP therapy), wherein the chimeric anti-CD20 antibody is produced from nucleic acid encoding a light chain variable region comprising the amino acid sequence in SEQ ID NO: 1 and a heavy chain variable region comprising the amino acid sequence in SEQ ID NO: 2, and comprises human gamma 1 heavy-chain and kappa light-chain constant region sequences.

4. A method for treating low grade or follicular non-Hodgkin's lymphoma (NHL) comprising administering to a patient a therapeutically effective amount of rituximab during a chemotherapeutic regimen, wherein the chemotherapeutic regimen consists of cyclophosphamide, vincristine, and prednisone (CVP therapy), wherein the method comprises administering 375 mg/m.sup.2 of rituximab once every 3 weeks for 8 doses, and wherein the method provides a beneficial synergistic effect in the patient.

5. A method for treating low grade or follicular non-Hodgkin's lymphoma (NHL) comprising administering to a patient 375 mg/m² of C2B8 once every 3 weeks for 8 doses during a chemotherapeutic regimen consisting of cyclophosphamide, vincristine, and prednisone (CVP therapy).

6. A method for treating low grade or follicular non-Hodgkin's lymphoma (NHL) comprising administering to a patient 375 mg/m² of a chimeric anti-CD20 antibody once every 3 weeks for 8 doses during a chemotherapeutic regimen consisting of cyclophosphamide, vincristine, and prednisone (CVP therapy), wherein the chimeric anti-CD20 antibody is produced from nucleic acid encoding a light chain variable region comprising the amino acid sequence in SEQ ID NO: 1 and a heavy chain variable region comprising the amino acid sequence in SEQ ID NO: 2, and comprises human gamma 1 heavy-chain and kappa light-chain constant region sequences.

Propofol – USA

On Nov. 07, 2018, Federal Circuit affirmed (Rule 36 judgment) Patent Trial and Appeal Board’s decision that a patent covering Fresenius’ Diprivan® is invalid.

Previously, PTAB on Jun 07, 2017 in IPR2018-00186 issued final written decision & found certain claims of US 8,476,010 (expiring on 06/01/2025) unpatentable under obviousness. The ’010 patent relates to pharmaceutical formulations of propofol that are stored in containers having nonreactive, inert closures. PTAB in summary considering the trial record as a whole found that the use of silicone oil on the rubber stoppers was repeatedly identified as a solution to normal rubber stopper problem. PTAB credited the testimony of Dr. Feinberg that a person of ordinary skill in the art would have had a reasonable expectation of success in substituting a siliconized rubber stopper for an uncoated rubber stopper. It also would have been expected that this substitution would not have resulted in less stability for the emulsion nor in increased propofol degradation. In doing so, PTAB determined that Petitioner has shown by a preponderance of the evidence that claims 1, 13–15, 17, 18, 20, and 24–28 are unpatentable as obvious over prior arts.

Pemetrexed - Italy

On Oct 15, 2018, The Court of Milan reversed first instance decision regarding method of use patent & found infringement.

Previously, by order of Sep 10, 2017, first instance Judge issued a declaration of non-infringement that antitumor drug “Pemetrexed Fresenius Kabi 100 mg” and “Pemetrexed Fresenius Kabi 500 mg” powder for concentrate for solution did not infringe the Italian portion of patent EP 1313508 owned by ELI LILLY. In short, in the first instance preliminary proceedings the Judge held that the literal wording of claims 1 and 12 showed that the patent claimed a specific chemical compound, i.e. the disodium salt of the antifolate pemetrexed (pemetrexed disodium), and this was confirmed by the description of the patent (whereby “the antifolate or antifolate drug for use in this invention” was exclusively “pemetrexed disodium (ALIMTA) as manufactured by ELI LILLY”), so that the alleged infringement by the petitioners’ product had to be excluded, on the grounds that it includes another component, i.e. pemetrexed diacid. In support of the above conclusion, the first instance Judge also relied on the file history of EP 1313508 and, in particular, on the progressive limitations introduced by the patent holder following the objections raised by the Examiner against the original wording of the patent application, which initially claimed the entire class of antifolates, was subsequently limited to the antifolate pemetrexed and then further limited, in its final version, to pemetrexed disodium alone. Therefore, the Judge concluded that this construction of the scope of protection of EP 1313508 excludes its infringement by equivalents because patentee limited the claim scope to pemetrexed disodium only.

Court of appeal however disagreed & said that in the present case, the reconstruction of the examination phase of EP 1313508 carried out by the Panel of Experts confirmed that an objection was raised against the first limitation submitted by ELI LILLY & Co., according to which the compound pemetrexed – which had replaced the wider term “antifolates” used in the original wording of claim 1 – could be challenged under Article 123, paragraph 2, EPC. In fact, this remark did not imply any objection of lack of novelty or lack of inventive step. It must be acknowledged that in such event – unlike limitations arising from prior art objections – a limitation introduced further to an objection of added matter cannot materially affect the application of the doctrine of equivalents, since such objection only concerns formal issues regarding the literal wording of the amended claims, as compared to the patent application as filed. Thus, in present case it can thus be safely ruled out that the amendment made by the applicant and introduced in the text as granted may per se be considered to restrict the interpretation of the patent’s scope of protection in such a manner as to exclude compounds that are equivalent to pemetrexed disodium.

Moreover, according to reply filed by Eli Lilly there was no intention to restrict the scope of protection to the pharmaceutical form of pemetrexed disodium. There is absolutely no hint of any such exclusion, especially considering that the invention does not regard the selection of a pemetrexed salt but is rather aimed at reducing the toxic effects of the active moiety of said active ingredient, i.e. the anion. As confirmed by the Panel of Experts, at the filing date of EP 1313508 the person skilled in the art was aware that the active moiety of the ingredient pemetrexed – i.e. the one capable of penetrating inside the cells and exerting both its inhibiting but also its toxic effects – is the anion & not salt. Therefore, the person skilled in the art would not attach any particular significance to the fact that the antifolate pemetrexed was in the disodium salt form. The person skilled in the art would treat this as a clearly non-essential element of the invention, since the invention is aimed to solve a clinical issue of toxicity by associating vitamin B12 to the active (and toxic) moiety of pemetrexed disodium, i.e. the anion.

The Panel of Experts thus next conducted the so-called “Triple Test” to assess whether – once literal infringement has been excluded – infringement by equivalents exists between pemetrexed fresenius and the pemetrexed disodium of EP 1313508. The Panel established that both have the same therapeutic function, highlighting the SmPC (Summary of Product Characteristics) portion of the Fresenius. The administration of Pemetrexed Fresenius according to the methods described in the SmPC – after reconstitution in 5% glucose solution and subsequent dilution of a powder containing also mannitol, hydrochloric acid and trometamol – necessarily leads to forming the anionic species having trometamol (or tromethamine) as a counterion instead of sodium. Since the active moiety is the same both in Fresenius’ pemetrexed diacid and in ELI LILLY & Co.’s pemetrexed disodium, and since such active moiety is used in combination with vitamin B12 and folic acid, the Panel of Experts concluded that the mechanism of action of Pemetrexed Fresenius is the same as pemetrexed disodium according to the medical use defined in EP 1313508.

The Panel of Experts thus concluded that Pemetrexed Fresenius infringes the scope of protection of patent EP 1313508 by direct equivalence.

Adalimumab - USA

Decision on IPR: Nov 02, 2018

AIA Review	Filing Date	Institution Date	Petitioner	US Patent	Respondent	Status
IPR2017-02105	09/14/2017	04/03/2018	Sandoz Inc.	9,090,689	AbbVie	Terminated - Settled
IPR2017-02106	09/14/2017	04/03/2018	Sandoz Inc.	9,067,992	AbbVie	Terminated - Settled

US 9,090,689 (AbbVie Biotechnology, Ltd; Exp: Jul 18, 2023)

1. A method of administering adalimumab for treatment of moderate to severe chronic plaque psoriasis, comprising filling adalimumab into vessels and subcutaneously administering 40 mg of said adalimumab to a patient having moderate to severe chronic plaque psoriasis every other week.

7. A method of preparing adalimumab for treating moderate to severe chronic plaque psoriasis, comprising filling adalimumab into vessels and providing said adalimumab for treatment, wherein said treatment comprises subcutaneously administering 40 mg of said adalimumab to a patient having moderate to severe chronic plaque psoriasis every other week.

US 9,067,992 (AbbVie Biotechnology, Ltd; Exp: Jul 18, 2023)

1. A method of treatment of moderate to severe active psoriatic arthritis in adult patients, wherein each said patient has .gtoreq.3 swollen and .gtoreq.3 tender joints prior to the treatment and has failed NSAID therapy, comprising subcutaneously administering to each said patient 40 mg of adalimumab every other week, wherein 23% of said patients achieve 70% reduction in American College of Rheumatology (ACR) score at week 24 of the treatment.

Ezetimibe & Simvastatin - Netherlands

On Oct 23, 2018, The Court of Appeal in interlocutory proceedings ruled that SPC for the combination product of ezetimibe and simvastatin is likely to be found invalid.

The Hague Court confirms in its preliminary opinion that the combination SPC for ezetimibe + simvastatin has been granted in violation of article 3 (c) of the SPC-Regulation as the combination is not the object of the invention protected by the basic patent. Also as interpreted by the CJEU, condition has not been met in this case, because SPC had already been granted for ezetimibe single product and the combination with simvastatin is not inventive concept of the Basic Patent.

The ruling of the Court of Appeal is in line with the earlier ruling of the District Court of Dusseldorf delivered on Oct 01, 2018 where Dusseldorf court revoked preliminary injunction granted based on same combination SPC.

Rituximab - USA

Decision on IPR: Oct 31, 2018

AIA Review	Filing Date	Institution Date	Petitioner	US Patent	Respondent	Final Written Decision
IPR2017-01168	04/28/2017	11/06/2017	Pfizer, Inc.	8,821,873	Biogen Inc.	Claims 1–5 are unpatentable

US 8,821,873 (Biogen Inc; Exp: Jul 28, 2020)

1. A method of treating a patient with diffuse large cell lymphoma comprising administering anti-CD20 antibody and chemotherapy to the patient, wherein the patient is >60 years old, wherein the chemotherapy comprises CHOP (cyclophosphamide, hydroxydaunorubicin/doxorubicin, vincristine, and prednisone/prednisolone), and wherein the anti-CD20 antibody is administered to the patient in combination with stem cell transplantation regimen.

5. A method of treating a patient with diffuse large cell lymphoma comprising administering rituximab and CHOP (cyclophosphamide, hydroxydaunorubicin/doxorubicin, vincristine, and prednisone/prednisolone) to the patient, in combination with stem cell transplantation, wherein the patient is >60 years old.