Filgrastim & Pegfilgrastim - USA

IPR decision: Jun. 23, 2020

 

AIA Review #	Filing Date	Institution Date	Petitioner	Patent	Respondent	STATUS
IPR2019-01183	06/08/2019	12/10/2019	Fresenius Kabi USA, LLC	9,643,997	Amgen Inc.	Terminated-Settled

On US’997, Kashiv bioscience filed IPR (IPR2019-00797) on 03/07/2019 which was terminated as parties settled.

US 9,643,997 (Amgen Inc.)

1. A method of purifying a protein expressed in a non-native soluble form in a non-mammalian expression system comprising: (a) lysing a non-mammalian cell in which the protein is expressed in a nonnative soluble form to generate a cell lysate; (b) contacting the cell lysate with a separation matrix under conditions suitable for the protein to associate with the separation matrix; (c) washing the separation matrix; and (d) eluting the protein from the separation matrix.

 

9. A method of purifying a protein expressed in a non-native limited solubility form in a non-mammalian expression system comprising: (a) solubilizing the expressed protein in a solubilization solution comprising one or more of the following: (i) a denaturant; (ii) a reductant; and (iii) a surfactant; (b) forming a refold solution comprising the solubilization solution and a refold buffer, the refold buffer comprising one or more of the following: (i) a denaturant; (ii) an aggregation suppressor; (iii) a protein stabilizer; and (iv) a redox component; (c) applying the refold solution to a separation matrix under conditions suitable for the protein to associate with the matrix; (d) washing the separation matrix; and (e) eluting the protein from the separation matrix.

 

 

CLENPIQ® - USA

On Jun. 22, 2020 Delaware Court granted Defendants’ Motion for Judgment on the Pleadings & did not find induced infringement of method of administration claims.

Civil Action No.   : 19-913

Plaintiffs               : Ferring Pharmaceuticals Inc. et al

Defendants          : Lupin Inc. et al

Before the Court is Defendants’ Motion for Judgment on the Pleadings pursuant to Federal Rule of Civil Procedure 12(c) for failure to state a claim upon which relief may be granted.

Background:

Plaintiffs filed this action on May 16, 2019, alleging infringement of U.S. Patent Nos. 9,827,23 and 9,669,110. The instant action is in response to Defendants filing an ANDA seeking FDA approval for a generic of Plaintiffs’ product, CLENPIQ® (sodium picosulfate, magnesium oxide, and anhydrous citric acid) Oral Solution. The ’231 patent claims a composition of sodium picosulfate, magnesium oxide, citric acid, and malic acid and methods for making and using the composition. The ’110 patent claims a method of timing a colonoscopy procedure. Only the ’110 patent is at issue in Defendants’ motion for judgment on the pleadings.

Claim 1 of the ’110 patent recites:

1. A method of timing a colonoscopy procedure performed on a patient in need thereof, comprising: administering a picosulfate bowel composition to the patient; and performing the colonoscopy procedure from about 3 hours to about 1 hour after the administration of the picosulfate bowel composition.

CLENPIQ® is indicated “for cleansing of the colon as a preparation for colonoscopy in adults.” The CLENPIQ® label describes a “Split-Dose Dosage Regimen,” which instructs:

First dose: administer during evening before the colonoscopy.

Second dose: administer the next day, during the morning prior to the colonoscopy.

The full prescribing information for the Split-Dose method for “second dose” reads:

Dose 2 – Next morning on the day of colonoscopy (start approximately 5 hours prior to colonoscopy):

• Continue to consume only clear liquids (no solid food or dairy).

• Take the second dose (the second bottle) of Sodium Picosulfate, Magnesium Oxide, and Anhydrous Citric Acid Oral Solution.

• Following the Sodium Picosulfate, Magnesium Oxide, and Anhydrous Citric Acid Oral Solution dose, drink at least three 8-ounce cups (cup provided) of clear liquids (24 ounces) at least 2 hours before the colonoscopy.

Court’ analysis:

Plaintiffs alleged that physicians and patients who use Defendants’ ANDA product in accordance with its label will directly infringe the claims of the ’110 patent by “performing the colonoscopy from about 3 hours to about 1 hour after administration of the picosulfate bowel composition.” Thus, Plaintiffs claim that Defendants will indirectly infringe the ’110 patent under 35 U.S.C. § 271(b) by inducing physicians who prescribe picosulfate solution, or patients who take it, to directly infringe. Defendants argued that Plaintiffs’ “complaint fails to state a claim [for induced infringement] because [Defendants’] ANDA label does not encourage, recommend, or promote anyone to perform the claimed use” of the ’110 patent. Regarding Dose 2, Defendants argued that because the label instructs physicians and patients to see the full prescribing instructions, and the full prescribing instructions direct that the 5.41-fluid ounce dose should be started “approximately 5 hours prior to colonoscopy,” the label therefore does not “encourage, recommend, or promote” that Dose 2 be taken less than 3 hours before the colonoscopy. Defendants continue that, even if “a patient could still be drinking the 5.41-fluid ounce dose within three hours of the colonoscopy” because the label is interpreted to “describe” or “permit” this use, the label does still not rise to the level of inducement because it is not encouraging, recommending, or promoting such use. Defendants claim that Plaintiffs cannot “create a material issue of fact” by asserting that it is possible for doctors and patients to infringe without showing that the label promotes or encourages that possible infringement.

Court agreed with Defendants & said that on its face, the label does not instruct that the Dose 2 picosulfate solution be administered less than 3 hours and more than 1 hour before the colonoscopy procedure. The label states that Dose 2 should be taken the “next day, during the morning of the colonoscopy.” It is a broad guideline for safe and effective timing of the second dose. The final step of the Split-Dose Regimen instructs that the patient should drink at least 24 ounces of clear liquid following the picosulfate solution but “at least 2 hours before the colonoscopy.” Logically, the instruction for the final step would require consumption of the picosulfate solution more than 2 hours before the colonoscopy. That instruction therefore cannot be interpreted as encouraging, recommending, or promoting consumption of the picosulfate solution less than 3 hours before the colonoscopy. The only reasonable reading of the full prescribing instructions is that they say to take the picosulfate solution no more than 5 hours before the colonoscopy and to finish it no later than 2 hours before the colonoscopy. The mere fact that the label may permit an infringing use is insufficient to show inducement, regardless of whether that fact is alleged in the complaint or stated later by an expert. See HZNP Medicines, 940 F.3d at 702. Thus, Defendants’ label cannot be the basis for a finding of any affirmative action or intent to induce infringement. Therefore Defendants’ label does not induce infringement of the ’110 patent.

Dimethyl fumarate – USA

On June 18, 2020, District Court of West Virginia found method of use patent covering Tecfidera® invalid for lack of written description support.

Background:

Biogen is the owner of US 8,399,514 patent entitled, “treatment for multiple sclerosis” expiring in Feb. 2028. This patent is listed in Orange Book for the product, Tecfidera® (Dimethyl fumarate) DR capsules. Biogen is the NDA holder & markets this product in USA.  Mylan sought approval of generic version & thus filed ANDA containing P-IV certification with USFDA to US’514 patent. Biogen sued Mylan within statutory period. Mylan also filed IPR in PTAB against same patent in Jul. 2018. PTAB issued final written decision in Feb. 2020 finding challenged claims not obvious over cited prior arts. Therefore, Mylan dropped obviousness challenge in district court & focused on lack of written description support under 35 U.S.C 112.

The independent claim 1 reads:

1. A method of treating a subject in need of treatment for multiple sclerosis comprising orally administering to the subject in need thereof a pharmaceutical composition consisting essentially of (a) a therapeutically effective amount of dimethyl fumarate, monomethyl fumarate, or a combination thereof, and (b) one or more pharmaceutically acceptable excipients, wherein the therapeutically effective amount of dimethyl fumarate, monomethyl fumarate, or a combination thereof is about 480 mg per day.

Court’s analysis:

Mylan argued that the ’514 Patent is invalid for lack of written description because the specification described in 2007 (priority date) bears no resemblance to the invention claimed in 2011. Specifically, at the time of filing POSA would not have expected the claimed invention——a 480mg/day dose of DMF (BID)——to effectively treat MS  and secondly when viewed as an integrated whole, the combination of selectively-plucked disclosures in the specification of the ’514 Patent fails to sufficiently describe the claimed invention. According to Mylan, it is only after Phase III trial in 2011 Biogen came to know the effectiveness of 480[mg/day] dose. Before the priority date of patent, only phase II results were known & that disclosed 720[mg/day] dose as effective dose to treat MS.

Court agreed with Mylan based on the facts, expert testimony & held that specification does not demonstrate that the Inventors “Possessed” the claimed invention at the time of filing of application. Court said that in order to satisfy the written description requirement of § 112, the inventor must “‘convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention, and demonstrate that by disclosure in the specification of the patent.’” Nuvo Pharm., 923 F.3d at 1376 (cleaned up) (citation omitted). Significantly, “actual ‘possession’ or reduction to practice outside of the specification is not enough.” Ariad Pharm. Inc., 598 F.3d at 1352. “[I]t is the specification itself that must demonstrate possession.” Court said that the specification of the ’514 Patent begins with a general discussion of MS but quickly turns to a discussion of how “the Nrf2 pathway may be activated in neurodegenerative and neuroinflammatory diseases as an endogenous protective mechanism.” The specification then provides five methods for screening of the compounds. Biogen argued that, “the ’514 Patent links through Method 4 each of the three recited elements of the asserted claims: (1) a method of treating MS with (2) DMF and/or MMF (3) at a dose of 480 mg per day.” But court said that Method 4 is limited in scope and makes no mention of treating MS with a 480mg/day dose of DMF (BID). Bioge then pointed out following paragraph from specification & argued that it provides support for the 480mg/day dose:

“For example, an effective dose of DMF or MMR to be administered to a subject orally can be from about 0.1 g to 1 g per pay [sic], 200 mg to about 800 mg per day (e.g., from about 240 mg to about 720 mg per day; or from about 480 mg to about 720 mg per day; or about 720 mg per day). For example, the 720 mg per day may be administered in separate administrations of 2, 3, 4, or 6 equal doses”.

Court said that this passage, however, neither “links” this “effective dose” to the treatment of MS, nor to a 480mg/day dose of DMF (BID). 480mg dosing is mentioned only once in this paragraph. Moreover, based on the results of Biogen’s Phase II study, as of the claimed priority date of February 8, 2007, a POSA would have known that 720mg/day of DMF (TID) is a therapeutically effective dose for treating MS, and that lower doses, such as 360mg/day of DMF (TID) and 120mg/day of DMF (QD), are not. Thus, on reading the specification, a POSA would be drawn to the 720mg/day dose of DMF because of its specific disclosure & not to 480mg dose. Moreover, this paragraph only discloses DMF & its dose. It does not discloses treatment of MS. Specification provides an exhaustive list of diseases that can be treated. Therefore, the method 4 can be used for a plethora of neurological diseases, and there are no “blaze marks” that would lead a POSA specifically to MS. Moreover, Biogen’s expert, Dr. Wynn, conceded on cross examination. Based on his reading of the ’514 Patent, he testified that he would not know which dose provided in this paragraph would be most effective for treating MS.

Biogen’s reliance on Example 3 fares no better which is an Experimental Autoimmune Encephalomyelitis (“EAE”) animal model used for MS. Dr. Wynn never explained how this experiment teaches a method of treating MS (in humans, not mice) with a therapeutically effective amount of DMF, i.e., 480 mg/day (BID). On the contrary, Dr. Lukashev credibly testified that the three examples in the ’514 Patent were part of his research, which “was separate from preclinical development” and unrelated to the clinical application of DMF in MS. Indeed, the results of Example 3 “provided evidence of [MMF] and [DMF] activation of NRF2 in vivo.”

Moreover, extrinsic evidence confirms the lack of written description. After getting the surprising results from phase III in 2011, Biogen filed different patent application (US 14/119,373) specifically covering the methods of treating Multiple Sclerosis with 480 mg/day dose. The specification provided and discussed in detail a wealth of data generated during Biogen’s Phase III study.  In contrast, the specification in the ’514 Patent included none of this data or information. But because of priority of May 2011, US’373 application would have faced strong invalidity challenges because of the ample availability of prior arts. Therefore, Biogen amended its title and claims of the US 12/526,296 application (parent of US’514 patent, now abandoned) without amending specification so that it can claim priority date of Feb. 2007. This strategy came with a cost, however, since Biogen was left with a specification written in 2007 that bore no resemblance to the ’514 Patent’s title and claimed invention——a method of treating MS with a therapeutically effective amount of DMF, i.e., 480mg/day —an invention that no one knew would work until April 2011 when Biogen received the results of its Phase III study.

Court said that, in sum, Biogen has attempted to satisfy the written description requirement of § 112 by selectively plucking specific words from the specification that correspond to each element of the claimed invention. The Federal Circuit has squarely rejected this approach. [Nuvo Pharm., 923 F.3d at 1380]. The ’514 Patent thus must be viewed as an integrated whole rather than a sum of its parts. As of February 8, 2007, inventors did not “possess” the claimed invention——a method of treating MS with a therapeutically effective amount of DMF, i.e., 480mg/day (BID) & thus Mylan has established by clear and convincing evidence that the asserted claims of the ’514 Patent are invalid for lack of written description.

Pomalidomide - USA

Claim Construction (District of New Jersey): Jun. 16, 2020

Civil Action No.: 17-3387

Plaintiff      : CELGENE CORPORATION

Defendants: HETERO LABS / AUROBINDO PHARMA / APOTEX INC. / MYLAN INC. / BRECKENRIDGE PHARMA / TEVA PHARMA

Before the Court is the parties’ request for claim construction. The Court held a Markman hearing on January 30, 2020.

This Markman decision involves four disputed terms from six patents stemming from two patent families: (i) United States Patent No. 8,198,262 (the “ʼ262 Patent”), United States Patent No. 8,673,939 (the “ʼ3,939 Patent”), and United States Patent No. 8,735,428 (the “ʼ428 Patent”), which are method of treatment (“MOT”) patents; and (ii) United States Patent No. 8,828,427 (the “’427 Patent”), United States Patent No. 9,993,467 (the “’467 Patent”), and the 10,555,939 (the ’5,939 Patent), which are formulation patents.

CONSTRUCTION OF DISPUTED TERMS:

1. “A method of treating multiple myeloma

Celgene: “A method of treating multiple myeloma” is limiting, such that the term requires efficacy in treating multiple myeloma

Defendants: “A method of treating multiple myeloma” is not limiting.

The Court: “A method of treating multiple myeloma” is not limiting.

2. “about 1 mg to about 5 mg per day of a compound having the formula [of pomalidomide] or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof” and “about 1 mg to about 5 mg of a compound  having the formula [of pomalidomide] or a solvate thereof

Celgene: “about 1 mg to about 5 mg per day of a compound having the formula [of pomalidomide] or a pharmaceutically acceptable salt, solvate, or stereoisomer containing about 1 mg to about 5 mg per day of a compound having the formula [of pomalidomide]” and “about 1 mg to about 5 mg per day of a compound having the formula [of pomalidomide] or a solvate containing about 1 mg to about 5 mg per day of a compound having the formula [of pomalidomide]”

Defendants: “about 1 mg to 5 mg ... of a compound having the formula [of pomalidomide] or about 1 mg to 5 mg of a pharmaceutically acceptable salt or solvate of [pomalidomide] or about 1 mg to 5 mg of any single stereoisomer of [pomalidomide]” and “about 1 mg to 5 mg ... of a compound having the formula [of pomalidomide] or about 1 mg to 5 mg of a solvate of [pomalidomide]”

The Court: “about 1 mg to about 5 mg per day of a compound having the formula [of pomalidomide] or a pharmaceutically acceptable salt, solvate, or stereoisomer containing about 1 mg to about 5 mg per day of a compound having the formula [of pomalidomide]” and “about 1 mg to about 5 mg per day of a compound having the formula [of pomalidomide] or a solvate containing about 1 mg to about 5 mg per day of a compound having the formula [of pomalidomide]”

3. “Lubricant”

Celgene: “a substance capable of reducing friction and/or reducing adhesion”

Defendants: “an excipient, in addition to the binder or filler, having the primary function of reducing

The Court: “a substance capable of reducing friction and/or reducing adhesion”

Pemetrexed – Netherlands

On Jun. 12, 2020, Supreme Court of Netherlands followed Advocate General’s Opinion and upheld preliminary injunction (PI) decision of lower court by dismissing the appeal.

The heart of the issue was the scope of the EP (NL) 1313508 patent which is held by Lilly. The patent entitled, “Combination containing an antifolate and methylmalonic acid lowering agent”. This second medical indication patent claims treatment of cancer with pemetrexed disodium in combination with vitamin B12 & folic acid. The patent is valid in the Netherlands until Jun. 14, 2021. Lilly markets the medicine Alimta® (Pemetrexed disodium). The active ingredient in Alimta® (after solution) consists of pemetrexed anions. In Alimta®, the anions are bound to sodium ions to form the pemetrexed disodium salt. The active substance in Fresenius Kabi's Pemetrexed for injection is Pemetrexed diacid with tromethamine instead of Pemetrexed disodium as in Alimta 100 mg / 500 mg powder for concentrate for solution for infusion. When reconstituted and diluted for administration, the active moiety remains the same irrespective of the salt form. The marketing authorization for Pemetrexed Fresenius was granted on July 22, 2016.

On Aug. 03, 2017 Lilly has claimed an infringement prohibition & argued that Pemetrexed Fresenius falls under the scope of protection of EP 508. Preliminary Relief Judge of the District Court of The Hague on Oct 24, 2017 issued an injunction against Fresenius Kabi’s pemetrexed product.  Court of Appeal of The Hague on May 08, 2018 affirmed the decision. Fresenius then appealed the decision. Advocate General Van Peursem provided opinion on Apr. 01, 2020 on the said matter. The actual assessment was done to see whether Pemetrexed Fresenius falls within the equivalent scope of protection of EP 508. Specifically, the question was whether the limitation of the claims introduced by Lilly during prosecution could preclude infringement under equivalence. During prosecution Lilly amended claims from antifolate to pemetrexed disodium. AG opined that in the eyes of the average skilled person, there is no conscious choice based on a technical reason, which would lead them to understand that the intention here is to claim only the disodium salt. According to the court, this technical choice cannot be deduced from the description by the person skilled in the art nor does the person skilled in the art read any indications that a salt study was carried out on which the choice for disodium salt. The average skilled person would see that disodium was just a suitable salt form. The disodium salt was only mentioned because it already existed (Alimta). The professional does not see such a deliberate limitation as intended by Fresenius on the basis of his general professional knowledge.

Moreover, the inventive idea of EP 508 lies in the use of vitamin B12 and optional folic acid in combination with the antifolate pemetrexed (not limited to pemetrexed disodium), thereby reducing the serious toxic side effects of the pemetrexed anions while the efficacy of the pemetrexed anions in the inhibition of tumor growth is maintained. The person skilled in the art knows that only the anion is responsible for the efficacy (and toxicity) of pemetrexed, he also finds confirmation for the insight that the invention relates rather to the active form of pemetrexed after administration and not to the specific disodium salt form disclosed therein , in the description of the mouse model.

Court of Appeal correctly considered that amendment to claims made during the granting procedure at the direction of the Examiner does not prevent a patent holder from relying on the application of Article 2 of the Protocol (equivalence) when determining the scope of protection. Claims were amended to avoid Art. 123(2) rejection (added matter) raised by Examiner. Added matter and scope of protection are clearly distinguishable issues. A limitation of the claims under Article 123 paragraph 2 EPC would result in the patent holder never being able to claim protection of equivalents. This could lead to too limited scope of protection.

Therefore, the appeal in cassation was dismissed & PI upheld.

Levocetirizine - USA

IPR decision: Jun. 09, 2020

AIA Review #	Filing Date	Institution Date	Petitioner	Patent	Respondent	Final Written Decision
IPR2019-00400	12/13/2018	07/15/2019	Apotex Inc.	8,633,194	UCB Biopharma Sprl	Claims 1–11 are patentable

US 8,633,194 (UCB Pharma; Exp: 10/16/2027):

1. A liquid pharmaceutical composition comprising (i) levocetirizine or a pharmaceutically acceptable salt of levocetirizine, and (ii) a preservative mixture consisting essentially of a mixture of methyl parahydroxybenzoate and propyl parahydroxybenzoate in a ratio of 9/1 expressed in weight, said mixture being present in an amount of more than 0 and up to 0.75 mg/ml of the composition, wherein said composition is substantially free of bacteria.

ORDER:

In consideration of the foregoing, it is hereby:

ORDERED that claims 1–11 of U.S. Patent No. 8,633,194 B2 are not determined to be unpatentable;

FURTHER ORDERED that Paper 44, Patent Owner’s Motion to Exclude Exhibits 1031–1038, 1040, 1041, and 1044 is denied;

FURTHER ORDERED that Paper 43, Petitioner’s Corrected Motion to Exclude Exhibits 2024, 2030, 2031, and 2034 is denied;

FURTHER ORDERED that Paper 18, Patent Owner’s First Motion to Seal is granted as to Exhibit 3005;

FURTHER ORDERED that Paper 28, Patent Owner’s Second Motion to Seal is granted as to Paper 27;

FURTHER ORDERED that Paper 35, the Parties’ Joint Motion to Seal is granted as to Exhibit 1039 only;

FURTHER ORDERED that Paper 35, the Parties’ Joint Motion to Seal is denied as to Exhibits 1042, 1043, and Paper 33 with leave to renew the request as set forth in section V(C)(2), above;

FURTHER ORDERED that, because this is a final written decision, parties to the proceeding seeking judicial review of the decision must comply with the notice and service requirements of 37 C.F.R. § 90.2.         

Dapsone – USA

On June 04, 2020, Federal Circuit denied Almirall’s request for attorney fees pursuant to 35 U.S.C. § 285.

Background:

Amneal filed IPRs against US 9,161,926 and US 9,517,219 patents in Feb. 2018 and in Oct. 2018 respectively. These patents are listed  in Orange Book for ACZONE® (dapsone) 7.5% topical gel. In Feb. 2019, Amneal filed ANDA with the FDA, submitting Paragraph IV certifications for the ’219 patent and the ’926 patent. Almirall sued amneal for infringement of ’219 patent only. Therefore, Amneal filed a counterclaim seeking declaratory judgment that the ’926 patent is invalid and is not infringed. After that parties engaged in settlement discussions between Apr. 22  - Apr. 29, 2019. It appeared that Almirall offered covenant-not-to-sue on the ’926 patent contingent on dismissal of this IPR. But the final settlement was not reached & in Aug. 2019 PTAB issued final written decision finding claims 1–6 of the ’926 patent not unpatentable. Amneal filed appeal on Oct. 28, 2019 & on Mar. 30, 2020, Amneal filed motion to voluntarily dismiss its appeal. Almirall thus sought attorney fees pursuant to 35 U.S.C. § 285. Almirall argued that Amneal litigated this matter in an unreasonable manner by continuing to litigate the IPR after the covenant-not-to-sue was offered, and Almirall had asked the FDA to remove the patent from the Orange Book. Almirall sought only fees and costs incurred during the relatively marginal window of time from [April 29, 2019], the date settlement negotiations were terminated, to the date of trial in the underlying IPR [June 5, 2019].

Court’s analysis:

Almirall specifically argued that Federal Circuit is authorised to award attorney fees in an appeal lies from the decision of PTAB. But, Federal Circuit disagreed & said that this court can award attorney fees under section 285 for work done in district court patent infringement actions. Appeals from the Board are a different matter as these are administrative proceedings. Moreover, the plain meaning of section 285’s reference to “[t]he court” speaks only to awarding fees that were incurred during, in close relation to, or as a direct result of, judicial proceedings. Though in some cases court has awarded attorney fees but these cases are different from present one. It is true that in Sullivan (Sullivan v. Hudson, 490 U.S. 877; 1989), the Supreme Court explained that fees could be awarded for administrative proceedings that are “intimately tied to the resolution of the judicial action and necessary to the attainment of the results Congress sought to promote by providing for fees.” But the “narrow class of qualifying administrative proceedings” that Sullivan was referring to were those “where ‘a suit has been brought in a court,’ and where ‘a formal complaint within the jurisdiction of a court of law’ remains pending and depends for its resolution upon the outcome of the administrative proceedings.” In another case, PPG (PPG Indus., Inc. v. Celanese Polymer Specialties Co., 840 F.2d 1565, 1569; Fed. Cir. 1988), this court allowed for the award of fees where Patent Office “proceedings substituted for the district court litigation on all issues considered by the PTO and the Board.” But it did so only with respect to fees incurred after the filing of a civil action, and the fees were awarded in that district court proceeding. The Patent Office proceedings were found by the district court to be intimately tied to the resolution of that action. Those are clearly not the circumstances here.

For these reasons, Federal Circuit rejected Almirall’s request for attorney fees under section 285.

Melatonin - UK

On Jun 03, 2020, UK high court denied Claimants, Neurim & Flynn’s application for interin injunction against Mylan.

Background:

Neurim owns patent, EP(UK) 1441702 which claims prolonged release pharmaceutical formulations of melatonin to improve the restorative quality of sleep in a patient suffering from primary insomnia characterised by non-restorative sleep. Flynn is the exclusive licensee under the Patent. The pharmaceutical formulation claimed by the Patent is sold under the brand name Circadin. More recently, Neurim has developed a paediatric version of prolonged release melatonin, Slenyto. The Patent is a “second medical use” patent & will expire on 12 August 2022. This patent was granted by EPO in May 2017 & was subsequently opposed by various opponents including Mylan. Patent was revoked by the EPO Opposition Division via written decision on 2 January 2020. Mylan intend to market a “generic” rival to Circadin as it got marketing authorisation in Dec. 2019.

Neurim and Flynn commenced proceeding for infringement and injunctive relief. Mylan counterclaims for revocation of the Patent on grounds of anticipation, obviousness and insufficiency. An expedited trial had been ordered, which is due to take place in a 5-day window floating from 26 October 2020. Hearing was held on the issue of interim injunction from May 20, 2020 to Jun 03, 2020.

Court’s analysis:

Neurim and Flynn argued that if an interim injunction were not granted, their losses would fall to be categorised under two broad heads, Period 1 (from hearing till trial i.e. from Jun. 2020 to Dec. 2020) and Period 2 (after trial till patent expiry i.e. Dec. 2020 to Aug. 2022). Mylan counterargued that the market would recover if Neurim and Flynn succeeded at trial and obtained a permanent injunction in Dec. 2020.

During hearing court heard both the parties & their respective submissions. Court said that the starting point for the current issue of interlocutory relief is the judgment given by Lord Diplock in “American Cyanamid Co v. Ethicon Ltd.” The court must weigh one need against another and determine where “the balance of convenience” lies. The balance of convenience involves a number of steps:.

Stage 1: A serious issue to be tried?

The applicant for interim relief, the claimant, must show that there is a “serious issue to be tried”.  Court said that looking simply at the issues in the proceedings, there is serious issue to be tried as to the validity of the Patent. In his oral submissions before me, Mr Vanhegan, QC, for Mylan, accepted that there was a serious issue to be tried.However, Mylan relied on the fact that the Patent had been revoked by the EPO Opposition Division in support of its contention that there was no serious issue to be tried. Mylan also argued that an interim injunction was refused in other jurisdictions. Court, however, said that in some cases, the decisions of courts of foreign jurisdictions or EPO are entitled to great weight but this is not one of those cases. The decisions of the these authorities are not binding on us.

Stage 2: Are damages an adequate remedy to the claimant?

If damages were an adequate remedy, a claimant should not obtain an interim injunction, even if the claim was very strong. Mylan contended that – even if, court found for the purposes of this application, the harm to Neurim and Flynn would extend beyond the period of competition between Circadin/Slenyto and the Generic Product in Period 1 – damages would nevertheless be an adequate remedy. Court agreed with Mylan and said that damages will prove to be an adequate remedy to both Neurim and Flynn for the following reasons:

    1.The general measure of damages in a patent infringement case is clearly stated. It is the standard tortious measure, the calculation of which was articulated in “Livingstone v. The Rawyards Coal Company”.

    2. Court see no reason why Neurim and/or Flynn’s losses during both Period 1 and Period 2 cannot properly be calculated. Clearly, Neurim and Flynn will have records of their sales to date of Circadin and Slenyto, and they will continue to keep such records. Equally, there is no difficulty in Mylan maintaining and (for the purposes of trial) providing to Neurim and Flynn records of its sales of the Generic Product.

    3. All of these losses/profits can be calculated by reference to information that is or will be in the hands of Neurim, Flynn & Mylan.

Stage 3: If damages are not an adequate remedy to the claimant, consider the adequacy of the undertaking in damages to the defendant?

If damages are an adequate remedy to the claimant, then the inquiry stops at Stage 2. However, the converse does not hold good. Court said that the question is whether Mylan’s loss, in being deprived of the opportunity of competing in the market for Circadin and Slenyto, is capable of being adequately compensated for in damages. Court said that Neurim and Flynn are prepared to offer the undertaking in damages; and that Neurim and Flynn are in a financial position to make good on that undertaking if called upon to do so. At first sight, just as in the case of Neurim and Flynn, this appears to be simply a case where damages can adequately be assessed. Instead of calculating what Neurim and Flynn lose by reason of Mylan’s competition, it is necessary in Mylan’s case to calculate what Mylan has failed to gain in being deprived of this opportunity. That said, there are a number of factors that render this assessment of damages more difficult. Therefore, it would be materially harder to assess Mylan’s loss than that of Neurim or Flynn.

Stage 4: no adequate remedy for either side

A court must consider all relevant factors when granting a discretionary remedy like an interim injunction. Court said that it already concluded that damages would be an adequate remedy for Neurim and Flynn, and a less adequate remedy for Mylan. Court said that it would merely go so far as to say that any award of damages to Mylan would be materially more uncertain than calculating Neurim and Flynn’s loss.

Court thus declined to grant interim injunction.

Beclomethasone & Formoterol - UK

On Jun 02, 2020, UK high court denied Claimant, Teva’s contention of “strike out” the infringement claim.

Background:

Defendant, Chiesi holds three patents, EP (UK) 2146704, EP (UK) 3034073, and EP (UK) 2010190, which essentially relate to a combination of beclomethasone and formoterol in an inhaler (DPI or MDI) for acute episodes of asthma attacks or for severe broncho-pulmonary diseases. These patents are due to expire in 2027/28. The defendants’ product is FOSTAIR, which is covered by these patents. Claimant, Teva commenced revocation action in Oct. 2019 against these patents. In its Defence and Counterclaim, Chiesi served infringement a quia timet basis, on the footing that the claimant threatens and intends to infringe. The case is listed for trial in October 2020, to be heard at the same time as a parallel claim between Lupin Healthcare (UK) Ltd and Chiesi . The defendant pressed the claimant for disclosure or a product description in relation to its product alleged to infringe. The claimant’s response was to apply to strike out the infringement claim. The strike out is brought primarily on the ground that the pleaded case has no real prospect of success. The claimant contends there is no evidence it threatens or intends to commit an infringing act and that no sufficient support for that allegation is pleaded in the Particulars of Infringement. Therefore, the infringement claim should be struck out.

Court’s analysis:

Court said that arguments about the basis for quia timet infringement actions come up from time to time in patent cases. The legal test is whether the relevant party threatens and intends to commit the act alleged to infringe. It is also important to have in mind that this is an application to strike out. That means that the question is not whether the pleaded material proves that the claimant threatens and/or intends to infringe, but only whether, based on the material pleaded, there is a real prospect of success of establishing that at trial.

Court said that based on witness statements claimant has put its case so far is that it has taken care to make no statement either way about its intentions. Counsel for the claimant argued that there was or should be a legal principle in patent cases that a quia timet action cannot proceed with no relevant marketing authorisation pleaded (Actavis v ICOS). Court said that the present case arises in circumstances referred to as “clearing the way”, where generic rival is thinking of entering the market by clearing hurdles such as patents associated with brand product. Like bringing court proceedings such as an action for patent revocation and/or declarations of non-infringement well before the generic launch on the market. And in this case claimant has initiated revocation proceedings against the patents. The starting point for such a claim is usually the simple inference from the fact claimant has brought revocation proceedings, that the rival presumably intends to infringe by launching a product within the period before expiry of the patent. That is a perfectly sensible inference to draw. Court thus said that there is no legal principle of the kind advanced by the claimant that a quia timet action cannot even be advanced without a marketing authorisation being pleaded. It cannot be derived from Actavis v ICOS. Moreover court noted that in “Generics v Sandoz [2017] EWHC 2276 (Pat)” in which Arnold J gave permission to allow a quia timet infringement claim to be added by amendment, there was no marketing authorisation in place at the time the decision was made.

Court said that it is important to be clear about timing. To commence a quia timet action in the first place the patentee has to show it has at that initial stage a real prospect of establishing that at trial – which may be months or years in the future – there is a sufficiently strong probability that an injunction would be required to prevent harm to the claimant occurring after trial. The question is not concerned with whether the rival may about to launch the product at the start of the action. So the fact there is no marketing authorisation in place when the claim form is issued, or otherwise when action begins, is not relevant. It is the existence of a threat and intention to start selling product sometime within the lifetime of the patent which justifies a quia timet infringement action.

With respect to pleadings of infringement, defendant relied on four points: the issue of the revocation proceedings, the expiry dates of the patents, the issue of equivalent revocation proceedings in Ireland where the claimant has a manufacturing facility which supplies the UK, and an exchange of correspondence. Court said that in this case the earliest expiry date for the patents is in 2027. The inference from the fact that the claimant has issued proceedings to revoke the patents in 2019 is that the claimant intends to sell a product protected by the patent before 2027. But, the claimant will need to obtain a marketing authorisation first to launch the product. The absence of a marketing authorisation today does not mean that there is no real prospect at trial of establishing a threat and intention to infringe. The claimant may have obtained a marketing authorisation by then. If the claimant had wished to say that it did not intend to launch unless it succeeded in revoking the patent, then it had a clear opportunity to do so in the exchange of correspondence. It did not. It is a reasonable inference from the claimant’s response in the present circumstances that the claimant wishes to reserve for itself the ability to choose to launch at risk using a product protected by the patents even if the patent(s) are found valid. The offer of two weeks’ notice does not allow the question of infringement to be decided in advance of launch. Court held that the defendant’s pleaded case has a real prospect of success at trial and court thus denied claimant’s application of strike out the infringement claim.

Buprenorphine & Naloxone

IPR decision: Jun. 02, 2020

AIA Review #	Filing Date	Institution Decision Date	Petitioner	Patent	Respondent	FINAL WRITTEN DECISION
IPR2019-00329	11/13/2018	06/03/2019	Dr. Reddy's Laboratories	9,687,454	Indivior UK Ltd	Some Challenged Claims Unpatentable

On US’ 454, DRL previously filed IPR IPR2019-00328 which was denied by PTAB on 06/03/2019.

US 9,687,454 (Indivior UK Limited; Exp: 08/07/2029) – OB listed

1. An oral, self-supporting, A mucoadhesive film comprising: (a) about 40 wt % to about 60 wt % of a water-soluble polymeric matrix; (b) about 2 mg to about 16 mg of buprenorphine or a pharmaceutically acceptable salt thereof; (c) about 0.5 mg to about 4 mg of naloxone or a pharmaceutically acceptable salt thereof; and (d) an acidic buffer; wherein the film is mucoadhesive to the sublingual mucosa or the buccal mucosa; wherein the weight ratio of (b):(c) is about 4:1; wherein the weight ratio of (d):(b) is from 2:1 to 1:5; and wherein application of the film on the sublingual mucosa or the buccal mucosa results in differing absorption between buprenorphine and naloxone, with a buprenorphine C.sub.max from about 0.624 ng/ml to about 5.638 ng/ml and a buprenorphine AUC from about 5.431 hr*ng/ml to about 56.238 hr*ng/ml; and a naloxone Cmax from about 41.04 pg/ml to about 323.75 pg/ml and a naloxone AUC from about 102.88 hr*pg/ml to about 812.00 hr*pg/ml.