Cabazitaxel - USA

On Sep. 21, 2017, Patent Trial and Appeal Board (PTAB) issued final written decision & concluded that claims of U.S. Patent No. 8,927,592 (expiring on Apr 27, 2031) are unpatentable. The ’592 patent, titled “Antitumoral Use of Cabazitaxel,” is directed to the use of cabazitaxel in the treatment of prostate cancer, particularly metastatic castration resistant prostate cancer (“mCRPC”).

Mylan Laboratories Limited (petitioner”) filed a Petition requesting an inter partes review of claims 1–5 and 7–30 of US’592. Petitioner asserts that the subject matter of claims would have been obvious to a person of ordinary skill in the art based on the combined teachings of Winquist and TROPIC. They together disclose the same treatment protocol described in Example 1 of the ’592 patent.

The fundamental dispute between Petitioner and Patent Owner concerns the relevant standard for evaluating whether a POSA would have had a reasonable expectation of “success” in achieving the claimed method. PTAB said that, Patent Owner attempted to raise the bar for the standard of “success” required to prove obviousness. Patent Owner’s argument is misplaced because it implicitly defines “success” as a clinically effective treatment where clinical benefit outweighs potential risks to the patient in the context of a phase III clinical trial designed for FDA approval.

Petitioner, therefore, need not establish a POSA reasonably would have expected successful phase III clinical trial results, FDA approval of cabazitaxel and prednisone combination therapy, or an actual increase in patient survival, to demonstrate obviousness of claims 1 and 27. (In re Montgomery, 677 F.3d, 1375, 1380 (Fed. Cir. 2012).

With respect to the secondary considerations, PTAB concluded that Patent Owner’s secondary considerations evidence does not outweigh Petitioner’s strong evidence of obviousness.

Pitavastatin - USA

On Sep 20, 2017, District court of New York issued decision upholding the validity of Livalo® (Pitavastatin) patent & found Amneal, Apotex infringing the Japanese drugmaker Kowa Co. Ltd’s patent. 

Kowa Co Ltd holds NDA for Livalo (Pitavastatin) tablet which was approved by USFDA on Aug 03, 2009. Orange book currently lists 4 patents. Kowa filed lawsuit against many ANDA filers in Apr 2014. 

While eight PIV cases were filed in defense of this product, only two ANDA applicants (Amneal and Apotex) completed trial which ended in Feb2017. In this case, the Court issued an Opinion concerning one patent (US5,856,336) which Amneal argued was invalid due to obviousness-type double patenting. As such, the District Court concluded that the ‘336 patent is valid. While no Final Judgment was entered, there is a second patent where Amneal and Apotex concluded trial over the US8,557,993 patent. New York federal judge delivered the verdict that Kowa’s patent US '993 was valid and that the defendants failed to show it was anticipated or obvious.

Tenofovir and Emtricitabine - France

On Sep. 05, 2017 the High Court of Paris issued its decision on the validity of the Gilead SPC on Truvada® covering tenofovir and emtricitabine.

Gilead Sciences Inc, is the holder of the supplementary protection certificate (SPC) no 05 C 0032 that is effectively valid until 24 February 2020, granted on the basis of the European Patent no 0915894, that expired as of 25 July 2017.  SPC covers the following combination : "tenofovir disoproxil and the salts, hydrates, tautomers and solvates thereof in combination with other therapeutic compounds such as emtricitabine" based on marketing authorisation of TRUVADA® in France.

The European Patent no 0915894 is entitled "nucleotide analogues", and covers compositions that are useful in the therapeutic treatment of several viral infections in humans or animals, in particular HIV. The compositions covered by this patent contain in particular tenofovir disoproxil, an active ingredient developed by the Gilead group for the treatment of viruses such as the HIV, and which may be used alone or, as provided for in claim no 27, in a pharmaceutical composition in combination with other therapeutic ingredients.

The Gilead group currently markets eleven medicaments for the treatment of HIV. Five of these drugs contain tenofovir disoproxil in the form of a fumaric acid salt, tenofovir disoproxil fumarate used :  VIREAD ® ,  as the sole active ingredient in the medicament

TRUVADA®, that combines tenofovir disoproxil with emtricitabine ;

ATRIPLA ®, that combines tenofovir disoproxil, emtricitabine, and efavirenz ;  

EVIPLERA ®, that combines tenofovir disoproxil, emtricitabine, and rilpivirine ;

STRIBILD ®, that combines tenofovir disoproxil, emtricitabine, elvitegravir, and cobicistat.

                                                         

In Dec 2016, Mylan received marketing authorisation for "Tenofovir disoproxil MYLAN", and "Emtricitabine  /  Tenofovir Disoproxil MYLAN". In France, the company MYLAN served summons in an action brought to invalidate the Gilead French SPC.

Court after analysing the relevant CJEU’s decision said that the claim no 27 is drafted so broadly that it does not describe any specific active ingredient that should be combined with tenofovir disproxil . It thus does not protect a combination that is likely to result in entitlement to the grant of a patent. Moreover, the combination claimed as active ingredient "tenofovir disoproxyl + emtricibatine" is not implicitly but necessarily and specifically taught in the description, there is no indication whatsoever that would enable the person skilled in the art to choose emtricibatine and it quite evidently does not constitute the core of the invention.

As a consequence, it is possible to say that the SPC is in all likelihood invalid and no preliminary injunction could be granted and requests of the GILEAD companies shall be dismissed.

Mesalamine – USA

On Sep. 12, 2017, Northern District of West Virginia issued an opinion ruling that Mylan’s proposed generic version of Apriso® does not infringe the asserted patent(s).

Salix / Valeant Pharmaceuticals hold an approved New Drug Application ("NDA") for Apriso® (Mesalamine) extended-release capsules.  It was approved by the United States Food and Drug Administration ("FDA") on Oct 31, 2008. There are total 07 patents listed in orange book (OB) of which 6 are expiring on Apr 20, 2018 & one US 8,865,688 is expiring on May 1, 2030.

Mylan Pharmaceuticals filed Abbreviated New Drug Application (ANDA) to the FDA seeking approval to market a generic version of Apriso®.  Salix sued Mylan in Jun 2015 in Northern District of West Virginia & court held bench trial in March 2017. Court decided that plaintiffs have not carried their burden to prove that Mylan’s ANDA product will infringe claim 1 of the ‘688 Patent either directly or indirectly.

Lupin is the first ANDA filer for this product & has settled the case.  Other filers are Novel & Teva. Novel’s case was dismissed in Jul 2017 & Teva’s case is under discovery.

In a parallel PTAB proceeding, on Dec. 08, 2015, Generico LLC filed Inter Partes Review over the US’688 patent & Mylan joined this IPR. On May 19, 2017, the Patent Trial and Appeal Board of the USPTO issued its Final Written Decision in an IPR proceeding & held that two claims in dispute (1 and 16) of the US’688 patent were obvious in view of the prior arts. This decision is under appeal at CAFC.

Apixaban - USA

On Sep 11, 2017, Chief Judge Leonard P. Stark of District of Delaware issued an opinion in Eliquis®; (Apixaban) case regarding motion to dismiss for improper venue by Mylan Pharmaceuticals Inc. (MPI) in light of the Supreme Court's recent decision in TCI Heartland LLC v. Kraft Food Group Brands (2017).

The venue motions are procedural - and therefore governed by the law of the regional circuit, even though the substantive questions at issue may be controlled exclusively by Federal Circuit law. Accordingly, the Court applied Third Circuit law to the procedural aspects of Defendant's improper venue motion, which places the burden on Defendant to prove improper venue. MPI, which has submitted an ANDA to the USFDA for permission to market and sell a generic version of one of Plaintiffs' (BMS/Pfizer) patent-protected drug products, bears the burden to show that it does not satisfy the requirements of the second prong of§ 1400(b).

The patent venue statute, 28 U.S.C. § 1400(b), provides:

Any civil action for patent infringement may be brought in the judicial district [1] where the defendant resides, or [2] [(a)] where the defendant has committed acts of infringement and [(b)] has a regular and established place of business.

On May 22, 2017, the Supreme Court issued its decision in TC Heartland, "hold[ing] that  a domestic corporation 'resides' only in its State of incorporation for purposes of the patent venue statute," adding that "amendments to § 1391 did not modify the meaning of§ 1400(b)." The Supreme Court did not construe the second prong of§ 1400(b), which makes venue in a patent case proper where a defendant "has committed acts of infringement and has a regular and established place of business”.

It is undisputed that under the Supreme Court's decision in TC Heartland, venue in this case is not proper in Delaware under the "resides" portion of the statute, as MPI is incorporated in West Virginia. MPI, therefore, "resides" in West Virginia, not Delaware.

The parties' dispute, then, is whether venue is proper in Delaware in accordance with the second prong of§ 1400(b). Venue in Delaware is proper under this portion of the statute unless MPI can show either that (a) MPI has not committed acts of infringement in Delaware, or (b) MPI does not have a regular and established place of business in Delaware.

(    a)    Acts of Infringement:

The first requirement of the second prong of § 1400(b) is that "the defendant has committed acts of infringement" in this District. The issue appears to be one of first impression because neither party nor court is aware of any case law related to this.

In a Hatch Waxman suit, the subject of the dispute is the generic drug product that the defendant will manufacture and sell and offer for sale in the future (after obtaining FDA approval) & not about a generic product the defendant has sold or is selling (Acorda Therapeutics Inc. v. Mylan Pharm. Inc., 817 F.3d 755, 760 (Fed. Cir. 2016). Thus, on the surface there appears to be a complete mismatch between the backward-looking nature of the patent venue statute and the forward-looking nature of Hatch-Waxman litigation.

What, then, does Hatch-Waxman define as an act of infringement? It is the submission of an ANDA to the FDA, if the ANDA seeks approval before the expiration of a patent covering the branded drug to which the generic product is bioequivalent (artificial-act of infringement).  An applicant submits an ANDA with full knowledge of the effect of its application and with the objective of marketing its drug product in the event that the application is approved. Thus, "Mylan' s [and MPI' s] ANDA filings, including, its certifications regarding the patents at issue here, were thus suit-related, and they had a substantial connection with Delaware because they reliably, non-speculatively predicted Delaware activities by Mylan”. This can be sufficient to demonstrate that the ANDA-filing Defendant "has committed" "acts of infringement" in this District.

(    b)   Regular and Established Place of Business:

In order for venue to be proper under the second prong of § 1400(b), the defendant must also have "a regular and established place of business" in the district.

In its mandamus petition, Cordis (Fed. Cir. 1985) invoked its lack of a fixed physical location as dispositive of the question whether it had a regular and established place of business in Minnesota. The Federal Circuit explicitly rejected this contention, holding that "in determining whether a corporate defendant has a regular and established place of business in a district, the appropriate inquiry is whether the corporate defendant does its business in that district through a permanent and continuous presence there and not ... whether it has a fixed physical presence in the sense of a formal office or store."

But in holding that no fixed physical presence in the sense of a formal office or store is required, Cordis should not be understood as eliminating the statutory requirement that a defendant have some regular and established ''place of business" in the venue. Consistent with what Judge had already determined before Cordis, the Court understands Cordis to mean that while no fixed space in the sense of a formal office or store is necessary, some physical presence is nevertheless required. Cordis' analysis focused on the defendant's physical presence in the district. Cordis' explanation that there needs to be a "permanent and continuous presence" in a district further confirms that the corporate defendant is required to have some sort of meaningful physical manifestation in the district. But as Cordis also demonstrates, this inquiry is factually driven and dependent on the circumstances of the case.

Pulling all of this together, the Court proceeded to analyze whether a defendant has a regular and established place of business in Delaware in the following manner. Based on both the statutory language of§ 1400(b) and Cordis, 729 F.2d at 737, the Court must determine whether a defendant has a regular and established place of business by conducting a fact intensive inquiry focused on whether the defendant does its business in this District through a permanent and continuous presence here. If all that is revealed by the record is that the defendant is registered to do business here, or only maintains a website that is accessible in Delaware, or simply ships goods to unaffiliated individuals or third-party entities here, then this District is an improper venue for the lawsuit.

Turning to the record presently before the Court, the Court is unable to determine whether MPI has a regular and established place of business in Delaware. Before the Court will evaluate whether MPI can show that it lacks a regular and established place of business here, the Court will provide BMS an opportunity to take venue-related discovery.

Such discovery will include understanding the relationships among the 40 Delaware Mylan entities and MPI. Venue in a patent infringement case [may be] proper with regard to one corporation by virtue of the acts of another intimately connected, corporation. It will also consider whether MPI (or any Mylan entity) has sales representatives who come to Delaware, who meet with doctors and hospitals here, what they do here, and how often they do it. The venue-related discovery may also include attempting to understand "the way that the industry operates, the way that sales are made, [and how] marketing and promotions are done." Further, it will explore details of MPI's (or another Mylan entity's) operations with wholesalers like McKesson, Americsource Bergen, or Cardinal Health. Finally, discovery will consider the extent to which MPI has relationships with "end users," such as pharmacies and physicians in Delaware, "that are aimed at incentivizing them to purchase MPI products from wholesalers and distributors.

CONCLUSION: For the reasons stated above, the Court denied without prejudice MPI' s motion to dismiss for improper venue. MPI has committed acts of infringement in Delaware based on its submission of an ANDA to the FDA, with the intention and for the purpose of selling products in Delaware that would allegedly infringe BMS' patents. The Court was not yet able to determine whether MPI lacks a regular and established place of business in Delaware. Hence, the Court will permit venue-related discovery and allow MPI to renew its venue challenge after such discovery is completed.

Nitric Oxide - USA

On Sep 05, 2017, District of Delaware issued its decision in INOmax® (Nitric Oxide) case & found patents-in-suit are invalid & not infringed by Defendants.

In this patent infringement action, Mallinckrodt Hospital Products IP Ltd., INO Therapeutics LLC, and Ikaria, Inc. (collectively, "Plaintiffs" or "Ikaria") alleged that Praxair Distribution, Inc. and Praxair, Inc. (collectively, "Defendants" or "Praxair") infringed the asserted claims of the patents-in-suit. The court held a seven-day bench trial in this matter, beginning on March 13, 2017. Specifically, Defendants alleged that U.S. Patent Nos. 8,282,966, 8,293,284, 8,795,741, 8,431,163, and 8,846112 (collectively, the "HF patents") are invalid under 35 U.S.C. § 101; Defendants argued that they do not infringe U.S. Patent Nos. 8,573,209, 8,776,794, 8,776,795, 9,265,911, and 9,295,802 (collectively, the "DSIR patents"); and U.S. Patent No. 9.279,794 (the "Sensor Drift Patent").

Invalidation:

The court's conclusion that the HF patents are invalid under§ 101 is supported by the marked similarity between the HF patents and the patents at issue in Mayo. The Court determined that, though human action is required by the "administering" step, the relationship between concentrations of metabolites in the blood and the effect of a dose of a thiopurine drug is a mere consequence of how a patient's body metabolizes thiopurine-an entirely natural process. Here, just like in Mayo, some of the claimed steps require human action. Nonetheless, the core of the alleged invention is the increased risk of pulmonary-capillary wedge pressure that develops when administering iNO to term or near-term patients with both hypoxic respiratory failure and left-ventricular dysfunction. That "invention" is really a patient populations' natural physiological response to 20 ppm of inhaled nitric oxide treatment. The court finds it abundantly clear that the claim limitations of the HF patents recite routine, conventional activity that does nothing to transform the law of nature at the core of the "invention." The court thus concluded that the HF patents are invalid under 35 U.S.C. § 101 because they disclose patent-ineligible subject matter without an inventive step that transforms that nature of the invention into something worthy of patent protection.

Infringement:

Praxair advanced a two-part non-infringement argument with regard to its ANDA for Noxivent. First, use of Noxivent with the DSIR device cannot directly infringe the claims of the DSIR patent because Noxivent is incompatible with the DSIR device. Second, even if the Praxair cylinder was "reasonably capable" of use with a DSIR device, as Plaintiffs' contend, such use would not satisfy the device or method claims of the DSIR patents. The court agreed with Praxair that its cylinders are incompatible with the DSIR system. There is no dispute that, without an INOmeter, the DSIR device will not deliver nitric oxide-the "therapy gas"-as required by all of the asserted claims of the DSIR patents.

Defendants did not dispute the validity of the sensor drift patent. Instead, they argued that they do not infringe. Because the sensor drift patent discloses a method and system implemented as a software upgrade to the DSIR. Defendant’s arguments for non-infringement closely followed their arguments for non-infringement of the DSIR device. The court, therefore, found that there could be no direct infringement of the sensor drift patent for similar reasons as those articulated above. Because the court finds no direct infringement, there also cannot be induced infringement of the '794 patent's method claims. Even if there was direct infringement, however, Praxair still does not induce infringement. The court will apply the same infringement standard it used when considering infringement of the DSIR patents.

Court finally having considered the entire record in this case and the applicable law concluded that the HF patents are invalid under § 101, and that Defendants do not infringe the “DSIR” or the “Sensor Drift” patents.

Methylphenidate - USA

On Sep 05, 2017, District court of Delaware issued its decision in Quillivant XR (methylphenidate ER suspension) case & found asserted claims of the patent-in-suit are invalid as obvious under 35 U.S.C. § 103.

In this Hatch-Waxman patent infringement action, plaintiff Tris Pharma, Inc. ("Tris") alleges patent infringement by defendant Actavis Laboratories FL, Inc. ("Actavis"). Plaintiff alleges that, by filing Abbreviated New Drug Applications ("AND As") seeking approval to market generic versions of Quillivant XR®, Defendant infringed U.S. Patent Nos. 8,46,765 ("the '765 patent"), 8,563,033 ("the '033 patent"), 8,778,390 ("the '390 patent"), 8,956,649 ("the '649 patent"), 9,040,083 ("the '083 patent"). The court held a five-day bench trial in this matter beginning on February 6, 2017.

Actavis challenged the validity of the asserted claims of the '765, '033, '390, '649, and '083 patents, arguing that a POSA would have found it obvious in light of the prior art to synthesize Qullivant XR® as an improved ADHD treatment. At the outset, the parties agreed that at the time of the invention, a POSA would have been motivated to make an extended release liquid methylphenidate product with an early onset of action and extended duration of effect. Actavis therefore contended that a POSA would have had both a motivation and more than a reasonable expectation of success in achieving that goal.

Aqueous MPH Formulation:  

Actavis argues that the prior art taught how to make stable liquid methylphenidate formulations having the pharmacokinetic characteristics and formulation details of the asserted claims. Specifically, Actavis relies on the combination of the Mehta, Ansel, and Connors references.  The Mehta reference discloses the use of ion exchange resin technology to make extended release formulations, including aqueous suspensions that identify methylphenidate as an active ingredient. Further Actavis relied on both the Ansel's and Connors prior art references to support its position that MPH at the claimed pH would have been obvious.

Despite Tris' arguments, for several reasons, the court was persuaded that there was a motivation to combine the teachings of the prior art references to achieve the MPH formulation, and that the skilled artisan would have had a reasonable expectation of success in doing so. In sum, the court was not convinced that the asserted claims include pH range limitations (pH of about 4 to about 4.5) that are critical to the claimed suspension's stability. Accordingly, the court concluded that Actavis has shown by clear and convincing evidence that a POSA would have been motivated to and have had a reasonable expectation of success combining MPH with water, at the claimed pH, in an ion-exchange resin to achieve the claimed liquid MPH product.

Pharmacokinetic Features & Clinical Effects:

The court next considered whether it would have been obvious to obtain the pharmacokinetic features and clinical effects of Quillivant XR®. Actavis contended that, despite the number of peaks being of little relevance to a POSA, the prior art disclosed Single Peak profiles with early onset of action and long duration of effect.

In response, Tris contended that the claimed PK features and clinical effects were not obvious. Specifically, Tris asserted that Actavis did not show why a POSA would have a reasonable expectation of success, be motivated, or have a reason to design a product with the clinical and PK features (such as Single Peak plasma profile) as claimed in a patent. In contrast, Tris further argued that, after the failure of Ritalin-SR®, the second generation of extended release solid oral MPH product-Concerta®, Metadate CD®, Ritalin® LA, and Focalin®-were developed using two components, IR and ER, to provide two peak (bimodal) profiles. Tris also contended that the state of the art second generation oral MPH products used bimodal profiles and delayed Tmax to extend effect.

While the court believed Tris' evidence regarding the second generation products is persuasive, it is not dispositive on the obviousness inquiry. Importantly, the Scicinski reference described the purpose of its invention as providing an oral dosage form of methylphenidate that has a long duration of action and rapid onset. Actavis' expert, Dr. Staller, testified that Scicinski Figure 7 discloses a target plasma profile for his methylphenidate product that has a Single Peak and a 12-hour duration of action.

Finally, although Tris' expert, Dr. McGough, testified that a POSA would not have expected a formulation with a single peak to achieve both early onset and extended duration of action, he admitted that he would "defer completely to a formulator in terms of what sort of curve could be achieved”.  As a result, the court finds the testimony of Actavis' formulator is more compelling. Accepting as credible Dr. Moreton's testimony that a formulator would have had no trouble achieving early onset of action and extended duration of effect with a Single Peak profile as of the priority date, the court finds Tris' arguments unpersuasive.

Buprenorphine & Naloxone - USA

On Aug. 31, 2017, Judge Richard G. Andrews of District of Delaware ruled that patents related to SUBOXONE (Buprenorphine & Naloxone) film are valid & not infringed by Defendants.

Plaintiffs Reckitt Benckiser Pharmaceuticals and MonoSol Rx, LLC (collectively, "Plaintiffs") brought this suit against Dr. Reddy's Laboratories; Watson Laboratories, Inc.; Par Pharmaceutical, Inc. and IntelGenx Technologies Corporation (collectively, "Defendants") with respect to U.S. Patent Nos. 8,603,514 ('"the '514 patent"); 8,900,497 ("the '497 patent") and 8,017,150 (the "'150 patent").

The '514 patent relates to Uniform Films for Rapid Dissolve Dosage Form Incorporating I Taste-Masking Compositions. The '497 patent relates to Process for Making a Film Having a Substantially Uniform Distribution of Components. The '150 patent relates to Polyethylene Oxide-Based Films and Drug Delivery Systems Made Therefrom.

Infringement:

Dried / Drying:

DRL argued that it does not infringe the "dried" limitation of the asserted claims of the '514 patent or the "drying" limitation of the asserted claim of the '497 patent. Court construed the term "dried" in the '514 patent to mean "dried without solely employing conventional convection air drying from the top." DRL argues that their ANDA process is "conventional" because -

(1) drying method used by DRL was ordinary and commonplace in the web coating industry as of 2001,

(2) DRL's ANDA products are dried solely using top air, and

(3) no bottom air or heat is used during the drying of DRL's products.

Plaintiffs argued that DRL's ANDA process is unconventional because it employs bottom drying. Court however did not agree and said that the DRL’s CL02 and CL03 dryers use a conventional exhaust system, which suggests that any bottom drying is at most a conventional amount. DRL's use of "bottom drying" is essentially that the inside of the oven simply gets hot and as a result, the bottom of film is incidentally heated. This is a conventional bottom drying method. If court were to find infringement, it would effectively be construing the drying limitation to claim all drying techniques that solve the drug content uniformity problem. This is not what the patents claim, however.

Visco-Elastic:

DRL argued that its drying process does not meet the visco-elastic solid film limitation of the '497 patent. Claim 1 of the '497 patent requires "rapidly evaporating at least a portion of said solvent upon initiation of drying to form a visco-elastic film within about the first 4.0 minutes to maintain said substantially uniform distribution of said at least one active by locking-in or substantially preventing migration of said at least one active within said visco-elastic film ....”

Court said that DRL's proposed product would lose about 20% of volatile solvent (water and alcohol) in about four minutes.  As a result, the majority of the wet matrix is still water. Rheological testing shows that the DRL's formulation is at best a visco-elastic liquid after four minutes of drying.

Drug Content Uniformity:

DRL argued that its ANDA products do not meet the drug content uniformity limitation of the '514 or the '497 patent. Court construed "without loss of substantial uniformity" to mean "such that individual dosage units do not vary by more than 10% from the intended amount of active for that dosage unit.”

Plaintiffs successfully established infringement of this limitation. DRL's ANDAs report drug content uniformity measurements for individual dosage units.

Viscosity:

DRL argues that its ANDA products do not meet the "viscosity" limitation of the '514 patent. Court construed the phrase, "said matrix has a viscosity sufficient to aid in substantially maintaining non-self-aggregating uniformity of the active in the matrix" to mean "viscosity sufficient to provide little to no aggregation of the active within the film." Viscosity plays a role to ensure that buprenorphine particles do not settle or aggregate. DRL's polymer matrix is specified to range between 5,000 centipoise to 20,000 centipoise. Further, the viscosity of all the tested lots fell within the "most preferred" range.

The ANDAs state that: "the selected compounding process ... results in acceptable drug uniformity in the final blend." Additionally, as discussed above, Plaintiffs establish infringement as to the drug content uniformity limitation. Plaintiffs have demonstrated that DRL infringes the viscosity limitation.

On similar lines Court also decided non-infringement in case of other defendants Watson & Par. Court concluded that for the foregoing reasons, Plaintiffs failed to meet their burden of showing that Defendants infringe claims of the '514 & 497 patents.

Invalidity:

Defendants argued that the asserted claims of the '514 and '497 patents are invalid as obvious. Defendants argued that a POSA would have been motivated to combine known techniques to achieve drug content uniformity. But court said that a POSA would not be motivated to combine the prior art to achieve drug content uniformity primarily because the POSA would have limited knowledge, and access to knowledge, of drying techniques. Based on the facts discussed above, a POSA would not have a reasonable expectation of success. Such a person would not have a strong grasp of prior web coating techniques to apply in the context of pharmaceutical films. A POSA would not have the experience of Dr. Gogolin with photographic film particulates, and bring it to bear into the context of pharmaceutical films. Court is not persuaded that such a POSA would be able to successfully resolve the issues with air bubbles and rippling. A POSA would have to engage in substantial experimentation in adjusting the mixing parameters, drying profile, and viscosity of the matrix to achieve drug content uniformity. A POSA would not have a reasonable expectation of success at achieving drug content uniformity.

Taking all of this evidence as a whole, Defendants have failed to demonstrate by clear and convincing evidence that the asserted claims of the '514 and '497 patents are invalid as obvious.

US’150 patent

With respect to the infringement of US’150 patent, the asserted claims required a water-soluble polymer component of PEO in combination with a HCP. The water-soluble polymer component comprises greater than 75% PEO and up to 25% HCP.

Plaintiffs argued that the sole infringement dispute is whether DRL, by substituting PVP for HCP in DRL's ANDA, infringes via the doctrine of equivalents. Defendants argued that Plaintiffs cannot apply the doctrine of equivalents to capture DRL's ANDA products because the patentees disclosed, but did not claim, PVP as an alternative to HCP. Plaintiffs argued that because there is no passage or example in the '150 patent specification that specifically discloses a combination of low and high molecular weight PEOs with PVP, the dedication-disclosure rule does not apply.

Court disagreed & said that it would be clear to a POSA reading the patent as a whole that PVP is disclosed as an alternative to the HCP element of the asserted claims. The strongest evidence that PVP can be used as an alternative to HCP is in the part of the specification where PEO, HCP, and PVP are listed as examples of useful water-soluble film-forming polymers. Further support is found in Example EA of the '150 patent, which describes films that include PEO and polyvinyl pyrrolidone (PVP) I polymeric blends." This example discloses that "the polymer component of the films contained about 80% PEO and 20% PVP, or a ratio of 4:1 PEO to PVP." Examples EI and EJ in Figure 38 also support the fact that PVP is an alternative to HCP. These examples are described as having similar properties to films made with polymer components comprised of PEO and HCP.

Because court found that the dedication-disclosure rule applies here, Plaintiffs failed to show that DRL infringes the '150 patent.

Oxymorphone - USA

On Aug. 30, 2017, Judge Richard G. Andrews of District of Delaware upheld a patent related to OPANA ER (Oxymorphone) tablet challenged by Teva/Actavis.

Plaintiffs Endo Pharma / Mallinckrodt brought this patent infringement action against Actavis defendants on Nov. 7, 2014, alleging that they had infringed U.S. Patent No. 8,871,779 ("the '779 patent") by filing ANDA 20-3930 seeking to enter the market with a generic version of Plaintiffs' Opana ER product, which is an extended-release oxymorphone tablet. The asserted claims of the '779 patent are all product claims directed to low-ABUK oxymorphone which is an impurity. In 2004, the FDA mandated that opioid manufacturers lower the levels of ABUK in opioid pharmaceuticals to less than 10 ppm.

Defendants argued that claims 1-6 of the '779 patent are invalid as obvious over the prior art.  Specifically, Defendants argued that a person of ordinary skill in the art would have been able to use routine methods known in the art to produce low-ABUK oxymorphone at the levels required by the FDA mandate. Defendants presented three "commonplace organic techniques" that they contend could be performed by "any graduate student" to produce low ABUK oxymorphone:

1) catalytic hydrogenation of the ABUK impurities;

2) sulfur addition to 10 separate out the ABUK impurities; and

 3) 0-demethylation of low-ABUK oxycodone into low ABUK oxymorphone.

Court rejected all arguments put forward by defendant & instead found Plaintiff’s expert testimony more convincing than defendant’s in reaching the decision on obviousness.

With respect to catalytic hydrogenation of the ABUK impurities, court found that that a person of ordinary skill in the art would have understood that it would not be feasible to simply run the reaction to completion as Dr. Gokel (Defendant’s expert) suggested. Longer the experiment runs, "the slower the reaction to remove the last bit of the material is going to be." Running the experiment for longer allows for side reactions to compete with the primary reaction and then "you'll start to hydrogenate other parts of the molecule and introduce other material.

With respect to sulfur addition to 10 separate out the ABUK impurities, court agreed with Plaintiffs and said that as an initial matter, court do not think Rapoport teaches that low- ABUK oxymorphone can be achieved through bisulfite addition combined with extraction. It seems that the poor partition ratio, combined with the lack of any examples of this method being used successfully, would not inform a person of ordinary skill that this was a promising method.

With respect to 0-demethylation of low-ABUK oxycodone into low ABUK oxymorphone, court again agreed with Plaintiffs and said that the starting material matters in evaluating whether a person of ordinary skill would have found low-ABUK oxymorphone obvious because 0-demethylation was available as a known method for converting oxycodone into oxymorphone. The person of ordinary skill at the time of invention would not have had access to the low-AB UK oxycodone Mallinckrodt used. As Plaintiffs point out, the prior art low-AB UK oxycodone had a different impurity profile that would result in differences in the final product of an 0-demethylation reaction. Therefore, Mallinckrodt's experiment is not relevant to the obviousness analysis.

Court also denied other grounds such as “anticipation” & “written description requirement”  and concluded that Defendants failed to prove by clear and convincing evidence that claims 1-6 of the '779 patent are invalid.