Saturday, March 30, 2019

Weekly Patent Litigation Roundup


Federal Circuit Reverses Patent Ineligibility Finding at Pleading Stage in Natural Alternatives
In Natural Alternatives Int’l, Inc. v. Creative Compounds, LLC, the Federal Circuit reversed the decision of the United States District Court for the Southern District of California, which had held that a series of patents owned by Natural Alternatives International, Inc. (“Natural Alternatives”) were directed to laws of nature and lacked an inventive concept sufficient to render them patent eligible under 35 U.S.C. § 101.…

Assertio therapeutics announces favorable NUCYNTA® patent ruling
LAKE FOREST, Ill., March 28, 2019 (GLOBE NEWSWIRE) -- Assertio Therapeutics, Inc. (NASDAQ: ASRT) today announced that the United States Court of Appeals for the Federal Circuit has ruled in favor of Assertio with respect to the company’s patent litigation against three filers of Abbreviated New Drug Applications (ANDAs) for the NUCYNTA® franchise. The Federal Circuit’s ruling affirms the decision of the United States District Court (D.N.J.), which found U.S. patent No. 7,994,364 (the ‘364 Patent) to be valid and infringed by the defendants. The ‘364 Patent covers the entire NUCYNTA® franchise until December 2025….

Teva Wins Patent Case Related to Orexo Opioid-Treatment Drug
A U.S. jury on Friday rejected a claim by Sweden’s Orexo AB that two generic opioid-addiction treatments created by Teva Pharmaceutical Industries Ltd. infringed a patent for Orexo’s biggest drug, Zubsolv. A Teva unit had created copies of the drugs Suboxone and Subutex, which are made by a third company, Indivior Plc, which wasn’t party to the lawsuit. Orexo had argued that the Teva products used the same essential formula as that covered by the patent for Zubsolv. After a trial in Wilmington, Delaware, federal court jurors disagreed….

Federal Court finds invalidity allegations relating to patent for metformin formulations not justified
On March 8, 2019, Justice Fothergill granted Valeant Canada’s application for an order prohibiting the Minister of Health from issuing a notice of compliance to Generic Partners for its generic version of Valeant’s GLUMETZA, a metformin formulation: Valeant Canada v Generic Partners Canada, 2019 FC 253…..

C-443/17 - Abraxis CJEU Judgement
The CJEU has today handed down judgment in the case C-443/17 (Abraxis Bioscience), link here (English version). Thank you to Andrew Hutchinson and Nicholas Fischer of Simmons & Simmons for providing some commentary on the decision. The CJEU’s full answer is as follows:
“Article 3(d) of Regulation (EC) No 469/2009 of the European Parliament and of the Council of 6 May 2009 concerning the supplementary protection certificate for medicinal products, read in conjunction with Article 1(b) of that regulation, must be interpreted as meaning that the marketing authorisation referred to in Article 3(b) of that regulation, relied on in support of an application for a supplementary protection certificate concerning a new formulation of an old active ingredient, cannot be regarded as being the first marketing authorisation for the product concerned as a medicinal product in the case where that active ingredient has already been the subject of a marketing authorisation as an active ingredient.”

Higher Regional Court Düsseldorf, 15 March 2019, docket no. I-2 U 62/18 – (Ezetimibe/Simvastatin)
On March 15, 2019 the Higher Regional Court Düsseldorf finally dismissed MSD’s request for a preliminary injunction based on their SPC for ezetimibe and simvastatin and thereby confirmed the result of the first instance decision of the Regional Court Düsseldorf of October 2018. The facts and background of the case, including the course of the proceedings before the Regional Court Düsseldorf, have already been reported on the EPLAW blog previously here….

Celgene settles Revlimid patent dispute with Alvogen
Celgene has settled its patent infringement litigation with would-be generic competitor Alvogen Pine Brook, LLC related to top seller Revlimid (lenalidomide). Under the terms of the settlement, Alvogen will be licensed to sell volume-limited amounts of generic lenalidomide in the U.S., assuming the FDA nod on its ANDA, on an undisclosed date after the March 2022 date the company previously granted to Natco. Alvogen will be able to sell its offering without restrictions beginning January 1, 2026.

Impax Blocked Access to Generic Version of Endo Drug, FTC Finds
Impax Laboratories LLC prevented access to a generic version of Endo Pharmaceuticals’ opioid pain reliever in an unlawful reverse payment scheme, the Federal Trade Commission announced March 29. Impax entered into an agreement with Endo, which is the brand maker of Opana ER, to block a generic version of the drug. Opana is an extended-release pain reliever. Its generic is called oxymorphone ER. The FTC sued Impax for allegedly accepting more than $100 million to delay its release of a...


Friday, March 29, 2019

Oxymorphone HCl – USA


On Mar 28, 2019 Federal Circuit reversed district court’s decision & found Opana® ER patent eligible under 35 U.S.C. § 101.

Endo owns U.S. Patent No. 8,808,737 (expiring on June 21, 2027) entitled “Method of treating pain utilizing controlled release oxymorphone pharmaceutical compositions and instruction on dosing for renal impairment.” The ’737 patent relates to his discovery that patients with renal impairment in need of pain relief can be treated in a new, different way than other patients. Specifically, the inventor discovered that patients with moderately or severely impaired kidney function need less oxymorphone than usual to achieve a similar level of pain management. And this can be determined based on correlation between plasma AUC for oxymorphone and a patient’s degree of renal impairment, as indicated by their creatinine clearance rate.

Claim 1 of the ’737 patent is representative and reads:

1. A method of treating pain in a renally impaired patient, comprising the steps of:
a. providing a solid oral controlled release dosage form, comprising:
i. about 5 mg to about 80 mg of oxymorphone or a pharmaceutically acceptable salt thereof as the sole active ingredient; and
ii. a controlled release matrix;
b. measuring a creatinine clearance rate of the patient and determining it to be
(a) less than about 30 ml/min,
(b) about 30 mL/min to about 50 mL/min,
(c) about 51 mL/min to about 80 mL/min, or
(d) above about 80 mL/min; and
c. orally administering to said patient, in dependence on which creatinine clearance rate is found, a lower dosage of the dosage form to provide pain relief;  wherein after said administration to said patient, the average AUC of oxymorphone over a 12-hour period is less than about 21 ng·hr/mL.

Endo and Mallinckrodt sued Actavis and Teva for allegedly infringing the ’737 patent’s claims 1−6. Actavis moved to dismiss Endo’s patent infringement claims, arguing that the patent claims were ineligible under § 101. The magistrate judge recommended granting Actavis’s motion. The magistrate judge first analyzed step 1 of the “Alice/Mayo” test, reasoning that the claims are directed to the natural law that the bioavailability of oxymorphone is increased in people with severe renal impairment. The magistrate judge then considered step 2 of the Alice/Mayo test, analyzing whether the ’737 patent claims, though directed to a law of nature, added enough to qualify as a patentable method that applies the law of nature. The magistrate judge separated claim 1 into three steps: (1) a “providing” step, (2) a “measuring” step, and (3) an “administering” step. First, the magistrate judge reasoned that the “providing” step is similar to the administering step in Mayo because it “merely identifies the specific drug for administration.” Second, the magistrate judge concluded that the measuring/determining step, like Mayo, “just directs one to use a well-known method to measure creatinine levels to obtain the necessary information to apply a law of nature.” Finally, the magistrate judge concluded that the “administering step” is indistinguishable from Mayo: “The administering step simply limits the relevant audience to patients and prescribing physicians, who treat chronic or acute pain with oxymorphone, and instructs the administration of the correct dosage of oxymorphone depending on the severity of the renal impairment, a step very similar to Mayo, which limited the relevant audience to “doctors who treat patients with certain diseases with thiopurine drugs.”

According to the magistrate judge, “the administering step merely instructs physicians to dispense oxymorphone for the treatment of pain in a well-known manner, while utilizing the natural law to manage the dosage.” Based on this analysis, the magistrate judge concluded that the patent was not directed to a patent-eligible application of a natural law. The district court adopted the magistrate judge’s recommendation, finding the patent claims ineligible.

During appeal Federal Circuit said that the Supreme Court has established a two-step framework to determine subject matter eligibility under § 101. [Alice Corp. Pty. v. CLS Bank Int’l, 573 U.S. 208, 217–18 (2014) (citing Mayo, 566 U.S. at 72–73, 75–80)]. Accordingly, at step one, “it is not enough to merely identify a patent-ineligible concept underlying the claim; we must determine whether that patent-ineligible concept is what the claim is ‘directed to.’” The Supreme Court has cautioned that “too broad an interpretation of” ineligible subject matter “could eviscerate patent law” because “all inventions at some level embody, use, reflect, rest upon, or apply laws of nature, natural phenomena, or abstract ideas.” Federal Circuit further said that the claims recite “[a] method of treating pain in a renally impaired patient” by providing, testing & administering limitations. Consistent with the claims, the abstract, patent title, and summary of the invention all describe the invention as a “method of treating pain” in patients with renal impairment. We held similar claims patent-eligible in “Vanda Pharmaceuticals Inc. v. West-Ward Pharmaceuticals International Ltd, 887 F.3d 1117 (Fed. Cir. 2018)”. The patent at issue in Vanda related to a method of treating schizophrenia patients with a drug (iloperidone), where the administered dose is adjusted based on whether or not the patient is a “CYP2D6 poor metabolizer.” The claims at issue here are legally indistinguishable from the representative claim in Vanda.

Also like the claims in Vanda, the claims here differ from those in Mayo in material respects. Although the representative claim in Mayo recited administering a thiopurine drug to a patient, the claim as a whole was not directed to the application of a drug to treat a particular disease. Furthermore, the administering step in Mayo is distinguishable from the administering step in the ’737 patent because the administering step in Mayo is the first step in the method that simply describes giving the drug to a patient with a certain disorder. By contrast, the administering step in the ’737 patent is the step that describes giving a specific dose of the drug based on the results of kidney function testing. The inventor here recognized the relationship between oxymorphone and patients with renal impairment, but that is not what he claimed. Rather he claimed an application of that relationship—specifically, a method of treatment including specific steps to adjust or lower the oxymorphone dose for patients with renal impairment. The claims are thus directed to more than just reciting the natural relationship. Moreover, the representative claim in Mayo stated that the metabolite level in blood simply “indicates” a need to increase or decrease dosage, without prescribing a specific dosage regimen or other added steps to take as a result of that indication. In contrast, the claims here recite the steps of carrying out a dosage regimen based on the results of kidney function testing. The claims require doctors to “orally administer to said patient, in dependence on which creatinine clearance rate is found, a lower dosage of the dosage form to provide pain relief” in such a way that after administering the dose, the patient’s “average AUC of oxymorphone over a 12-hour period is less than about 21 ng·hr/mL.” These are specific treatment steps. The claims prescribe a specific dosage regimen through the wherein clause, under which the physician administers oxymorphone to achieve a specific range of AUC of oxymorphone based on the patient’s creatinine clearance rate.

Federal Circuit disagreed with Actavis’s interpretation of the claims in view of Vanda. Court said that the wherein clause identifies the appropriate schedule and dose of oxymorphone to administer, as a function of how much oxymorphone is in the patient’s system. It is the combination of the administering step and wherein clause claim language, taken together, that make the claims-at-issue as specific as those in Vanda such that the patent claims do not “tie up the doctor’s subsequent treatment decision.” Like the administering step in Vanda, the administering step and wherein clause in the present claims allow the claims to do more than just recognize a need to lower or decrease a dose. Court finally held that the ’737 patent claims are not directed to patent-ineligible subject matter & therefore it reversed the district court’s decision.

Thursday, March 28, 2019

Tadalafil - UK


On Mar 27, 2019 The UK Supreme Court ruled in favour of Actavis (Teva) and Mylan in a dosage patent dispute against Eli Lilly over Cialis®.

The dosage patent which is the subject of this appeal is EP(UK) 1173181, which is owned by ICOS and exclusively licensed to Eli Lilly. It relates to the use of tadalafil in a dosage form for the treatment of Erectile Dysfunction (ED). It claims a pharmaceutical dosage form of about 1 to about 5mg of tadalafil in a unit dosage form suitable for oral administration for the treatment of sexual dysfunction, including ED up to a maximum total dose of 5mg per day. Tadalafil is a second in class of phosphodiesterase (PDE) drug. It is another PDE5 inhibitor and operates in essentially the same way as sildenafil. An advantage which tadalafil was found to have over sildenafil was its selectivity; it was able to bind to and inhibit its target PDE5 while having significantly less effect than sildenafil on other PDE families and, in particular, PDE6. This selectivity resulted in less and a smaller number of side effects.

Prior art, Daugan patent, EP 0839040 specifically describes tadalafil. Daugan discloses tadalafil’s potency (ie IC50) against PDE5 as 2 nM. Daugan further discloses that doses of tadalafil will generally be in the range of 0.5mg to 800mg daily for the average adult patient. It gives examples of a tablet containing a 50mg dose of the active ingredient. But the Daugan patent does not discloses an appropriate dosage regime as an oral treatment of ED.  In overturning the decision of Birss J, the Court of Appeal found patent invalid, based on the findings of fact at first instance, that the disclosure in Daugan would have highly motivated a skilled person to pursue tadalafil in clinical trials. Eli Lilly appealed.

The central question in this appeal was whether in the light of the common general knowledge and the Daugan patent as the nearest prior art, the relevant claims in the ‘181 patent were obvious. Specifically, whether it was obvious thing for the skilled team to conduct a further dose ranging study or studies to investigate lower doses and determine the minimum effective dose. Lilly asserted that the essence of the invention is the discovery that tadalafil is effective in treating ED at such a low dose and with minimal side effects. This discovery has allowed the drug to be taken daily (for chronic use) rather than on demand, thus avoiding the need to anticipate when sexual activity might occur. Lilly claims that this is a significant technical advantage as sildenafil by contrast is approved for on-demand use only. Lilly also argued that it was not obvious to try a low dose like 5mg per day as there was no reason to think that it would be effective at that dosage. Lilly further said that to invalidate the claim, it would be necessary to show that at the start of the clinical programme it was obvious to the skilled team that a 5mg/day dose would be safe and effective and also would have the minimal PDE5 related side effects.

Supreme Court considered both the “Windsurfing/Pozzoli” test and the EPO’s “problem/solution approach”, noting that both are glosses on the statutory provisions and that neither should be applied in a mechanistic way. Court further said that the factors which are relevant considerations in the present case include the following (Generics (UK) v Lundbeck):
1.    whether at the priority date something was “obvious to try”;
2.    the routine nature of the research and any established practice of following such research;
3.    the burden and cost of the research programme;
4.    the necessity for and the nature of the value judgments which the skilled team would have in the course of a testing programme;
5.    the existence of alternative or multiple paths of research;
6.    the motive of the skilled person is a relevant consideration;
7.    unexpected or surprising effect;
8.    use of any hindsight, which includes knowledge of the invention, in addressing the statutory question of obviousness;
9.    whether a feature of a claimed invention is an added benefit in a context in which the claimed innovation is obvious for another purpose.

Supreme Court said that the target of the skilled person’s research is in large measure pre-determined. The skilled person would aim for a dose as low as possible consistent with effectiveness. That would normally be the appropriate dosage regime. Court recognized and respected Birss J’s finding of fact that there was no defined standard of minimal efficacy in relation to ED and that this would require the skilled team to make a value judgment. But he also found that it was common general knowledge that regulators were often interested in and could require evidence of the minimum effective dose and that the skilled team would be familiar with multiple dose ranging studies as necessary as a generality. Court said that in its view, the inventiveness of the dosage regime falls to be assessed in that context. Bearing in mind that symmetry, the starting point in the assessment of obviousness in this case is the Daugan patent. One begins therefore with the assumption that the Daugan patent has enabled the skilled person to perform the invention of the use of tadalafil for the treatment of ED. That involves finding the appropriate dosage regime having regard to safety, tolerability and effectiveness. The procedures to achieve that end are familiar and routine as the Court of Appeal found in its judgement. Kitchin LJ gave the leading judgment, in which he adopted a fact specific assessment based on the facts of this case and involving the weighing up of several factors, and Floyd and Lewison LJJ agreed with his reasoning and conclusions. The fact that a 5mg dose was so much lower than the 50mg dose, which was recommended for sildenafil, mentioned in the Daugan patent for tadalafil, and used in the notional skilled team’s Phase IIa tests, is neither here nor there. The lack of an expectation of efficacy at a 5mg dose is a factor of little weight if, as was found, the skilled team would be very likely to study such a dose in the search for a dose response relationship. For the same reason the fact that the effectiveness of tadalafil at a dose of 5mg was a surprise can carry little, if any, weight. Similarly, the finding that there was an important value judgment to be made when the therapeutic plateau was identified at the same time as a marketable dose can bear little weight when there is a finding, which is not tainted by hindsight, that the skilled team would continue their tests.

Lilly also argued that the daily dosing regimen by which a person prescribed tadalafil can take the drug once per day rather than on demand in expectation of sexual activity was enabled by the technical effect of the drug, namely the maintenance of efficacy with minimal side effects, which was not obvious and which justified the patent. Court disagreed for two reasons. First, the judge correctly treated the daily dosing regimen as obvious because it was the result of the inevitable discovery of the half-life of tadalafil in Phase 1 of the tests. Secondly, claims 7 and 10 are not confined to the daily dosing regimen but also cover on demand use of the drug subject to a maximum total dose of 5mg per day. It was obvious to embark on that exercise and carry out tests in a routine way until that appropriate dose was ascertained. Those tests included the completion of the dose-ranging studies which were the purpose of Phase IIb. The fact that tadalafil at the dose of 5mg, while remaining effective as a treatment of ED, also, and unexpectedly, had the additional benefit of reduced side effects was an added benefit which does not prevent the identification of 5mg as the appropriate dose from being obvious. The completion of the Phase IIb dose ranging studies led to the asserted invention. In this case the trial judge’s findings of what would have been the sequence of the tests, which did not depend upon hindsight, included the finding, which the evidence clearly justified, that the team, having found a therapeutic plateau, would be very likely to test lower doses and so come upon the dosage regime which is the subject matter of the patent.

Therefore ‘181 patent is invalid for lacking an inventive step.


Sunday, March 17, 2019

Job Update

................................................................................

Function: IPR-Biotech

Company: Strides pharma

Location: Bangalore

Positions: Executive / Sr. Executive

Experience: 2-4 years

Qualification: M pharmacy/Science (Biotech)

Contact info:
aprajita.bigpharmajobs@gmail.com

................................................................................

Many thanks to my friend Mr Tushar Rane for sending this job update. If you know or have any vacancy in your IP department then you can drop me an email: mahen_gunjal@yahoo.co.in

Saturday, March 16, 2019

Asenapine – USA


On Mar 14, 2019 Federal Circuit vacated & remanded district court’s judgment regarding validity & non-infringement.

Defendants, Sigmapharm, Hikma, Breckenridge, Alembic & Amneal filed ANDA with USFDA seeking to market generic versions of Saphris, a drug product sold by Forest Laboratories, LLC. Saphris is a sublingually administered, atypical antipsychotic containing asenapine maleate. Forest sued for patent infringement, asserting that Defendants proposed generic products would infringe claims 1–2, 4–6, and 9–10 of U.S. Patent No. 5,763,476. Following a bench trial, the district court held Defendants had not established claims 1–2, 4–6, and 9–10 to be invalid and held Forest had not established infringement of claims 4, 9, and 10 as to Alembic and Breckenridge. Defendants then appealed the district court’s construction of claim 1 and its determination that the claims have not been established to be invalid. Forest cross-appealed, arguing that the district court’s finding that Breckenridge and Alembic do not infringe claim 4 was clearly erroneous.

Claims 1 and 4 recite:

1. A pharmaceutical composition comprising as a medicinally active compound: trans-5-chloro-2-methyl-2,3,3a, 12b-tetrahydro-1H-dibenz[2,3:6,7]oxepino[4,5-c]pyrrole or a pharmaceutically acceptable salt thereof; wherein the composition is a solid composition and disintegrates within 30 seconds in water at 37° C.

4. A method for treating tension, excitation, anxiety, and psychotic and schizophrenic disorders, comprising administering sublingually or buccally an effective amount of a pharmaceutical composition comprising trans-5-chloro-2-methyl-2,3,3a, 12b-tetrahydro-1H-dibenz[2,3:6,7]oxepino[4,5- c]pyrrole or a pharmaceutically acceptable salt thereof.

I. Construction of Claim 1:

While claim 4 is expressly limited to sublingual or buccal formulations of asenapine, claim 1 is not and instead states that “the composition is a solid composition and disintegrates within 30 seconds in water at 37° C.” The district court nevertheless construed claim 1 to be limited to buccal and sublingual formulations. Appellants argued that the district court erred in construing claim 1 this way. But Federal Circuit saw no error in the district court’s construction.  Federal Circuit said that although claim 1 does not expressly refer to buccal or sublingual administration, the claims “must be read in view of the specification, of which they are a part.” Phillips v. AWH Corp., 415 F.3d 1303, 1315 (Fed. Cir. 2005) (en banc) (quoting Markman v. Westview Instruments, Inc., 52 F.3d 967, 979 (Fed. Cir. 1995)). That construction is further supported by additional language in the specification, which explains the benefits of sublingual and buccal treatment over the prior art. The patent is also expressly titled “Sublingual or Buccal Pharmaceutical Composition.” The specification states that “[p]referred pharmaceutical compositions are solid pharmaceutical compositions which rapidly disintegrate in the mouth of a subject, upon insertion into the buccal pouch or upon placement under the tongue.” This strongly suggests that the language “the composition is a solid composition and disintegrates within 30 seconds in water at 37° C” was meant to limit the claim to buccal and sublingual formulations. Therefore, district court properly construed claim 1 to be limited to buccal and sublingual formulations.

II. Obviousness:

The district court found that Appellants had not established that there was a motivation to combine asenapine maleate into a sublingual or buccal form, and even if there were a motivation to combine, a skilled artisan would not have had a reasonable expectation that it would work. During appeal Appellant argued that an ordinarily skilled artisan would have been motivated to administer asenapine maleate sublingually or buccally to address known compliance concerns. Second, they argued that an ordinarily skilled artisan would have been motivated to administer asenapine maleate sublingually or buccally to obtain more treatment options. Federal Circuit said that the district court already discussed compliance concerns and, citing testimony from Forest’s expert witness Dr. McIntyre, explained that “clinicians with experience in treating schizophrenic patients understand that sublingual dosage forms are more burdensome to schizophrenic patients in that they require the patient to hold the dosage form in the mouth under the tongue for a period of time, and also require that the patient refrain from drinking or swallowing for a period of time.” The court further explained that Appellants’ “own expert clinician, Dr. Hollander, agreed that sublingual administration would not improve patient compliance. Turning to Appellants’ second claimed motivation, Federal Circuit held that the district court did not clearly err in rejecting Appellants’ contention that the benefits of having multiple treatment options available would provide a motivation to combine. The district court did not clearly err, however, in concluding that a generic need for more antipsychotic treatment options did not provide a motivation to combine these particular prior art elements.

Finally, Appellants argued that the district court erred in treating the claimed invention as providing a solution to an unrecognized problem in the art. District court found that the Organon scientists discovered a “previously unknown” problem and developed the claimed sublingual dosage forms as a solution to that problem. Specifically, it found that during early clinical studies Organon discovered intravenous and oral administration of asenapine resulted in severe cardiotoxic events. As a result, those studies were terminated prior to completion. The district court found, however, that during subsequent testing on beagles, while there was “a clear trend of increased heart effects with an oral tablet,” “no such trend was observed with the sublingual forms.” The district court found that while Organon became aware of these problems, “[t]here was nothing in the prior art that would have indicated that the oral tablet had problems.” The district court further held that the solution Organon developed to address the cardiotoxic effect was also non-obvious. Therefore, Federal Circuit saw no clear error in the district court’s consideration of the unknown nature of the problem solved by the inventors and the factors that would teach away from their solution.

Federal Circuit however, in light of the district court’s failure to make an express finding as to whether compliance concerns for patients with trouble swallowing would provide a motivation to combine, remanded this issue to the district court to address it further.

Long-Felt Need: Appellants pointed to evidence that the claimed invention did not satisfy a long-felt but unmet need. Specifically, they argued there were a variety of antipsychotic drugs available at the time of the invention, there is evidence that physicians did not switch treatment preferences for patients with schizophrenia when Saphris entered the market, and there is evidence that Saphris did not have better efficacy or compliance than other antipsychotics available in 1994. They further argued that Saphris itself has many side effects and a high discontinuation rate. Federal Circuit said that in reviewing the district court’s fact findings, we do not ask whether evidence could have supported the opposing view, only whether the district court clearly erred. Here it did not. Although there were a variety of existing antipsychotics, they had debilitating negative side effects, which evidence indicates are reduced in Saphris. Thus, the district court did not clearly err in finding it weighs in favor of non-obviousness.

Unexpected Results: Here, the district court found it was “surprising and unexpected” that the claimed “sublingual route of administration successfully resolved the serious cardiotoxic event reported in the ’476 patent.” However, as the district court found, there was nothing in the prior art that indicated cardiotoxic problems existed with other routes of administration. At the time of the claimed invention, a person of ordinary skill could not have been surprised that the sublingual route of administration did not result in cardiotoxic effects because the person of ordinary skill would not have been aware that other routes of administration do result in cardiotoxic effects. The district court, therefore, erred in its analysis of unexpected results.

III. Written Description:

Appellants argued that the specification fails to describe asenapine free base in a rapidly disintegrating, sublingual, or buccal solid composition. The district court’s finding that the specification contains sufficient written description support for claims 1 and 4 was not clearly erroneous. Appellants’ expert witness Dr. Gould acknowledged asenapine free base was known in the art. The specification repeatedly refers to pharmaceutical compositions containing asenapine free base.

IV. Infringement of Claim 4:

The district court found Breckenridge and Alembic do not infringe claim 4 directly, indirectly, or under the doctrine of equivalents. Breckenridge and Alembic’s proposed generic products are indicated for the treatment of “manic episodes” associated with bipolar I disorder. Claim 4 is directed to “a method for treating tension, excitation, anxiety, and psychotic and schizophrenic disorders.” The court construed claim 4 to not cover the treatment of bipolar disorders. The claim language and the specification indicate that “excitation” refers to a symptom rather than a “disorder. Moreover, experts for both parties agree that there is no such thing as an “excitation disorder,” further indicating the claim covers treatment of the symptom “excitation” rather than treatment of an “excitation disorder.” Although excitation may be a symptom of bipolar I disorder, the district court nevertheless carved bipolar I disorder out of its construction because it concluded that the “language of the ’476 patent is directed to ‘diseases’ and ‘disorders,’ not to symptoms of such.” This misreads the plain language of the claims and specification. Because the district court erred in treating “excitation” as being limited to “excitation disorders,” Federal Circuit vacated its finding of non-infringement and construed “excitation” to refer to a symptom and remanded to the district court to assess infringement in light of this construction.

CONCLUSION:

Federal Circuit thus vacated the district court’s judgment that Claims 1 and 4 are not invalid and remanded for it to consider the limited question of whether compliance concerns with patients who have trouble swallowing would provide a motivation to combine and its impact on the obviousness analysis. Federal Circuit also vacated district court’s judgment of non-infringement of claims 4, 9, and 10 as to Breckenridge and Alembic and remanded for the court to consider whether Breckenridge and Alembic infringe under revised construction.

Thursday, March 14, 2019

Suboxone® and Subutex® - USA


On Mar 12, 2019 Delaware court denied Orexo's motion for summary judgment as it failed to meet its burden to establish the requirements for issue preclusion.

Background:

In February 2017, Orexo filed this action. Orexo alleges in its complaint that Actavis Elizabeth's manufacturing and Actavis Pharma' s distribution of generic versions of Suboxone® and Subutex® infringe the US 8,454,996 patent. In their answer to the complaint, Defendants asserted as an affirmative defense and counterclaim that "one or more claims of the #996 patent are invalid under one or more provisions of 35 U.S.C. §§ 101, 102, 103, and/or 112. Defendants, however, now seek only to assert that the #996 patent is invalid under§§ 103 and 112. Orexo filed motion for summary judgment based on issue preclusion in previous Zubsolv® case.

In an earlier case filed in this court, Orexo sued Actavis alleging, among other things, that Actavis generic versions of Zubsolv® infringe the #996 patent. In response to Orexo's complaint in the Zubsolv litigation, Actavis Elizabeth and Actavis, Inc. asserted as an affirmative defense and in a counterclaim that claims of the #996 patent are "invalid under one or more provisions of 35 U.S.C. §§ 101, 102, 103, and/or 112." However, at trial Actavis presented only theory of invalidity based on obviousness. In an opinion issued on November 15, 2016, Judge Robinson held that the asserted claims of the #996 patent "are not invalid as obvious" and that Actavis Elizabeth infringed the asserted claims. Actavis Elizabeth did not appeal this ruling.

Analysis:

"The court shall grant summary judgment if the movant shows that there is no genuine dispute as to any material fact and the movant is entitled to judgment as a matter of law." Orexo argues in its summary judgment motion that "validity is a single issue" as a matter of law and that, therefore, the doctrine of issue preclusion bars Defendants from challenging the validity of the #996 patent in this action. Defendants disagree that validity is a single issue, but they do not dispute that if validity is deemed to be a single issue then the Actavis entities are precluded from challenging the #996 patent's validity in this action. In their papers filed in opposition to Orexo' s motion, Defendants asserted as a factual matter that "[t]he identical issue of the [#]996 patent's validity was not previously litigated" in the Zubsolv litigation. In support of this assertion, Defendants stated that§ 112 defenses they intend to assert in this action and certain prior art references they intend to offer as part of an obviousness defense under§ 103 in this action were not presented in the Zubsolv litigation. Orexo does not dispute that § 112 and the prior art references cited by Defendants were not presented or adjudicated in the Zubsolv litigation. Orexo simply contends that Defendants are precluded from asserting these invalidity defenses in this action because validity is a single issue and "validity under § 103 was actually litigated, adjudicated, and necessary to the judgment [in the Zubsolv litigation.

Court said that in a patent case, Third Circuit law governs the application of issue preclusion generally, and Federal Circuit law governs those aspects of issue preclusion "that may have special or unique application to patent cases." The doctrine of issue preclusion, sometimes called collateral estoppel, bars "' successive litigation of an issue of fact or law actually litigated and resolved in a valid court determination essential to the prior judgment,' even if the issue recurs in the context of a different claim." Taylor v. Sturgell, 553 U.S. 880, 892 (2008) (quoting New Hampshire v. Maine, 532 U.S. 742, 748-49 (2001)). Parties dispute whether the identical issue was previously litigated and adjudicated in the Zubsolv litigation (requirements 1 and 2) and whether Teva was fully represented in the Zubsolv litigation (requirement 4). Resolution of the parties' dispute with respect to the first and second requirements of issue preclusion hinges on the question of whether, as a matter of law, invalidity is a single issue for purposes of issue preclusion. Court further said that neither the Third Circuit nor the Federal Circuit has addressed whether validity is a single issue for estoppel purposes. But at least 12 courts in other districts have confronted the question; each court treated validity as a single issue. But in this case Judge Connolly of Delaware court declined Orexo's invitation to adopt a per se rule that validity is a single issue for purposes of issue preclusion. His decision was largely informed by authorities not cited by the parties: Blonder-Tongue Laboratories, Inc. v. University of Illinois Foundation, 402 U.S. 313 (1971). He also found that treating validity as a single issue as a matter of law conflicts with important policies underlying the issue preclusion doctrine and the federal patent laws.

Blonder-Tongue : In Blonder-Tongue, the Supreme Court abandoned the requirement of mutuality of parties for issue preclusion and explicitly overruled Triplett. The Court's analysis in Blonder-Tongue makes clear that it understood invalidity to encompass multiple issues for purposes of issue preclusion. The Court's references to "all issues concerning patent validity" and "relitigating validity issues", and its comparison of nonobviousness to "other questions on which patentability depends," demonstrate that the Court deemed nonobviousness an issue separate from (albeit within) the broader subject of invalidity. If validity were a single issue, then there would be no reason for the district court to make a "determination that the issue in both actions was identical" where the patent was found to be invalid in the first action. That district courts are required to make that determination when a defendant seeks to preclude a plaintiff from relitigating the validity of a patent previously held to be invalid necessarily means that validity is not a single issue.

Third Circuit and Federal Circuit Case Law: The legal rules that govern the invalidity defenses available to defendants sued for infringement vary significantly. A patent is invalid under§ 101, 102, 103 or 112 and each defense requires different legal standard.  There is, in short, no uniformity among the rules that govern the invalidity defenses afforded to an accused infringer. Accordingly, applying Third Circuit and Federal Circuit precedent, court found that validity should not, as a matter of law, be treated as a single issue for estoppel purposes.

Also public policies underlying the patent laws and the doctrine of issue preclusion counsel against adopting a per se rule that validity is a single issue. Treating validity as a single issue conflicts with the "well-established policy of freely allowing challenges to the validity of claimed intellectual property protection." Nasalok, 522 F.3d at 1327.

Because validity is not a single issue for estoppel purposes and because Orexo does not challenge Defendants' factual assertion that the invalidity defense presented in the Zubsolv litigation is not identical to the invalidity defense Defendants seek to present in this action, Orexo has failed to meet its burden to establish the first two requirements for issue preclusion to apply. Therefore court denied Orexo's motion for summary judgment.

Wednesday, March 13, 2019

Pneumonia vaccine - USA


Decision on IPR: Mar 13, 2019

AIA Review
Filing Date
Institution Date
Petitioner
US Patent
Respondent
Final Written Decision
IPR2017-02131
09/19/2017
03/22/2018
Merck
9,492,559
Pfizer Inc.
claims 1–10, 16–19, & 38–45 are  unpatentable
IPR2017-02132
09/19/2017
03/22/2018
Merck
9,492,559
Pfizer Inc.
claims 1–10, 16–19, and 38–45 are unpatentable
IPR2017-02136
09/19/2017
03/22/2018
Merck
9,492,559
Pfizer Inc.
claims 11–15 and 20–37 are unpatentable
IPR2017-02138
09/19/2017
03/22/2018
Merck
9,492,559
Pfizer Inc.
claims 11–15 and 20–37 are unpatentable
Previously Merck also filed other IPRs (IPR2018-00187 & IPR2018-00188) on 11/20/2017 of which IPR’187 was instituted & IPR’188 was denied by PTAB.

US 9,492,559 (Pfizer Inc.; Exp: Jan 15, 2035) :

1. An immunogenic composition comprising a Streptococcus pneumoniae serotype 22F glycoconjugate, wherein the glycoconjugate has a molecular weight of between 1000 kDa and 12,500 kDa and comprises an isolated capsular polysaccharide from S. pneumoniae serotype 22F and a carrier protein, and wherein a ratio (w/w) of the polysaccharide to the carrier protein is between 0.4 and 2.

Sunday, March 10, 2019

Job Update


  • ....................................................................................

Function: IPR-Formulation

Company: Optimus pharma

Location: Hyderabad

Experience: 2-4 years

Qualification: M pharmacy/pharmaceutics

Contact info:
Raghavender.k@optimuspharma.com

....................................................................................

Many thanks to my friend Mr Tushar Rane for sending this job update. If you know or have any vacancy in your IP department then you can drop me an email: mahen_gunjal@yahoo.co.in

Sunday, March 3, 2019

Weekly Patent Roundup


UK court overturns Genentech patent, cites Brexit in CJEU referral [Taltz (ixekizumab)]
The patents division of the English High Court has found that a patent owned by Genentech is invalid and denied the biotechnology company’s application for a supplementary protection certificate (SPC)…..


Last Remaining Defendant Settles FTC Suit that Led to Landmark Supreme Court Ruling on Drug Company “Reverse Payments” [AndroGel (Testosterone)]
The Federal Trade Commission has reached a settlement in FTC v. Actavis, the 2009 FTC case alleging that the brand-name drug company Solvay and three generic drug companies illegally agreed to restrict generic competition to Solvay’s branded testosterone-replacement drug AndroGel for nine years…..


Judge orders Boehringer to disclose Humira biosimilar plans
A US judge has ordered Boehringer Ingelheim to release its rollout plans for a biosimilar version of Humira (adalimumab), following a request from AbbVie. On Friday, February 22, Judge Richard Lloret granted AbbVie’s request to compel the release of more information about Boehringer’s launch plans for the arthritis medication….


Hikma Case Set for Supreme Court Consideration [Fanapt (iloperidone)]
Hikma Pharmaceuticals USA Inc. v. Vanda Pharmaceuticals Inc. (Supreme Court 2019). Briefing is now complete in this important eligibility case pending before the Supreme Court. Hikma’s petition presents the following question.
Whether patents that claim a method of medically treating a patient automatically satisfy Section 101 of the Patent Act, even if they apply a natural law using only routine and conventional steps…..


No Sovereign Immunity for Patent-Asserting State University
UF’s asserted patent is titled “Managing Critical Care Physiologic Data Using Data Synthesis Technology.” U.S. Patent No. 7,062,251.  From the patent title, keen Patently-O readers will recognize a potential eligibility problem.  N.D.Fla. District Court Judge Mark Walker dismissed the case on a R.12(b)(6) motion without taking any evidence — finding the asserted claims ineligible as a matter of law. On appeal, the Federal Circuit has affirmed…..


Amgen prevails in PCSK9 patent dispute with Regeneron and Sanofi
A Delaware jury has confirmed the validity of two Amgen  patents covering high cholesterol med Repatha (evolocumab), specifically, the antibodies that bind to a specific region on PCSK9 and reduce LDL-C ("bad" cholesterol) levels in the body. The verdict follows a March 2016 trial where competitors Regeneron Pharmaceuticals and Sanof  admitted that their PCSK9 inhibitor Praluent (alirocumab) infringed on Amgen's patents (unheld by a prior jury)……


Boehringer Must Show How IP 'Thicket' Blocked Humira Rival
Law360 (February 25, 2019, 5:39 PM EST) -- Boehringer Ingelheim must hand over its launch plans for a biosimilar version of AbbVie Inc.’s hugely popular immunosuppressant Humira, a Delaware magistrate judge has ruled in a patent infringement case, finding...


Saturday, March 2, 2019

Cyclosporine – USA


On Feb 26, 2019, District Court for the District of Columbia tossed Teva’s suit because of lack of standing as Teva didn’t show evidence that it would suffer an imminent injury.

Plaintiff, Teva brought this action to obtain “immediate injunctive and declaratory relief” barring the USFDA from “depriving [Teva] of its statutory right to 180 days of marketing exclusivity for its generic version of the brand-name drug Restasis®.” Teva alleges that it qualifies as the “first applicant” to submit a Paragraph IV certification for Restasis® and that, as a result, it is entitled to 180 days of generic exclusivity. Teva fears, however, that its statutory right will be extinguished once the FDA applies the interpretation of “first applicant” it recently espoused in a letter decision relating to another drug. To avoid that loss, Teva seeks a declaratory judgment that (1) the FDA’s interpretation of “first applicant” in that letter decision is invalid under the Administrative Procedure Act (“APA”) and that (2) Teva is entitled to the 180-day exclusivity period. Teva also seeks to enjoin the FDA from “approving any [ANDA] that references Restasis® . . . other than Teva’s ANDA” during the pendency of this litigation unless that ANDA meets Teva’s definition of “first applicant.”

Background:

Allergan received FDA approval to market Restasis®, a pioneer drug to treat dry eye, on December 23, 2002. Allergan originally listed two patents associated with Restasis® in the Orange Book: US 4,839,342 and US 5,474,979. The ‘342 patent expired on August 2, 2009, and the ‘979 patent expired on May 17, 2014. Shortly before the ‘979 patent expired, Allergan added five new Restasis®-related patents to the Orange Book, beginning with US 8,629,111, which issued on January 14, 2014. The ‘111 patent is the subject of the Paragraph IV certification at issue here.

Teva filed its ANDA for cyclosporine on January 23, 2012. At the time, the “only unexpired patent listed in the Orange Book” for Restasis® was the ‘979 patent. That patent was due to expire in May 2014, and Teva filed a Paragraph III certification, indicating that it intended to enter the market after the ‘979 patent expired. According to Teva, the FDA’s initial review of its ANDA was “plagued by irregularities.” Teva alleges that the FDA failed to act on its ANDA for nearly fifteen months. Finally, the FDA issued a letter “notif[ying] Teva that it was refusing” to receive “the company’s ANDA,”—a decision the agency later rescinded in June 2015. While Teva “was considering its response to the [FDA’s letter],” the USPTO issued the ‘111 patent. That same day—January 14, 2014—Teva amended its ANDA to include a Paragraph IV certification with respect to the ’111 patent. On July 9, 2015, thirty months after Teva submitted its ANDA, the FDA issued a formal acknowledgment letter deeming Teva’s ANDA “received . . . as of January 23, 2012.” Teva, in turn, timely dispatched its Paragraph IV notices to Allergan and the ‘111 patentees. Meanwhile, the FDA indicated that “one or more” ANDAs containing “[P]aragraph IV certifications to the ‘979 patent” were submitted “before January 14, 2014.”

In late 2015, the FDA opened a docket to solicit comments regarding the 180-day exclusivity period for generic cyclosporine. The FDA revealed that “one or more” applicants had filed an ANDA containing a Paragraph IV certification referencing the ‘979 patent before the ‘111 patent was issued on January 14, 2014; however, notice was not provided to the patent owners and NDA holder because the ‘979 patent expired before the FDA accepted any ANDA for review. The FDA then sought comment on two questions:

1.       Whether “[t]he one or more applicants that submitted ANDAs or patent amendments with [P]aragraph IV certifications” with respect “to the ‘979 patent” are “first applicants” for purpose of the 180-day exclusivity.
2.       Whether that  applicant (or those applicants) forfeited generic drug exclusivity “on May 17, 2014, when the ‘979 patent expired, such that no ANDA applicant for [c]yclosporine [o]phthalmic [e]mulsion, 0.05%, is eligible for 180-day generic drug exclusivity.

Six companies responded. Four answered yes to both questions. Teva and Akorn responded no. To date, the FDA has yet to issue a decision addressing either of these questions in the cyclosporine ANDA docket, and it has represented that it will not do so before it determines that an “ANDA applicant for cyclosporine has . . . satisfied the requirements for approval.”

In October 2016, the FDA published its final rule implementing portions of the MMA. According to Teva, the Final MMA Rule clearly provides that “eligibility for 180-day exclusivity requires timely notice of the exclusivity-qualifying Paragraph IV certification;” therefore, only those who have provided notice can qualify as first applicants. The FDA disagrees, arguing that the final rule “simply does not address the circumstance . . . where an applicant with a substantially complete ANDA containing a [P]aragraph IV certification is not able to provide valid notice . . . because the relevant patent expires before the FDA sends [the applicant] an Acknowledgement Letter.”

In July 2018, the FDA issued a letter decision in an unrelated matter, which addressed this question. (“Suboxone Letter Decision”). In that matter, “on May 14, 2013, one or more first applicants submitted a substantially complete ANDA (or an amendment to a substantially complete ANDA)” for a generic version of Suboxone® “with a Paragraph IV certification.” That applicant (or those applicants), however, subsequently withdrew their application(s) and “informed [the] FDA that [they] had not given notice to the NDA holder or patent owner.” “At least one other applicant submitted a substantially complete ANDA (or an amendment to a substantially complete ANDA)” referencing Suboxone® “after May 14, 2013, with a Paragraph IV certification and provided notice to the NDA holder and patent holder.” On those facts, the FDA concluded that the May 14, 2013 applicant qualified as the “first applicant” and, “[a]bsent forfeiture,” would have been “eligible for 180-day exclusivity.” The applicant, however, forfeited its right to exclusivity when it withdrew its application, and, because the “first applicant” did not qualify for 180-day exclusivity, the FDCA imposed “no barriers to approval of subsequent applicants.” Significantly, the FDA noted that exclusivity did not roll over to the subsequent applicant. FDA thus concluded that the “first effective approach” is inconsistent with “the statutory definition of ‘[f]irst [a]pplicant’ as defined by Congress in the MMA,” and that a “first submitted approach” better coheres with the current version of the FDCA. This event triggered the present suit among other things the preliminary injunction.

Present suit:

Court said that “a preliminary injunction is an extraordinary remedy never awarded as of right.” To secure a preliminary injunction, a plaintiff “must establish that he is likely to succeed on the merits that he is likely to suffer irreparable harm in the absence of preliminary relief, that the balance of equities tips in his favor, and that an injunction is in the public interest.” Court said that before applying the four-part test, however, the Court must address a threshold issue: whether it has jurisdiction over Teva’s claim.

Teva challenges the FDA’s interpretation of “first applicant” in the Suboxone Letter Decision and contends that, if allowed to stand, that reading of the MMA will deprive Teva of its statutory right to 180 days of generic exclusivity for cyclosporine. According to Teva, the FDA erred as a matter of substance because the MMA definition of “first applicant” not only requires that the applicant be the first to file a substantially complete ANDA, but also requires that the applicant timely effect notice (i.e., the “first effective approach”). Teva also argues that the Suboxone Letter Decision must be set aside because it was issued in violation of the procedural requirements of the APA. In support of its motion for preliminary relief, Teva contends that each of the relevant factors tip in favor of issuing a preliminary injunction. For the reasons explained above, Teva contends that it is likely to prevail on the merits. It further argues that, unless the FDA is enjoined, “application of the [Suboxone] Letter Decision to Teva’s cyclosporine ANDA will harm Teva irreparably by divesting the company of its statutory right to 180-day exclusivity and imposing at least $50 million in losses that Teva can never recover.” Finally, Teva maintains that the balance of hardships and public interest weigh in favor of granting a preliminary injunction.

Court said that it cannot reach the merits of Teva’s APA challenge or its motion for a preliminary injunction, without first addressing standing, and, as the record now stands, Teva has failed to clear that threshold hurdle. Teva contends that it has pled two types of injuries sufficient to establish standing:

Loss of Exclusivity:

The parties agree that the loss of generic exclusivity is a concrete injury sufficient to confer standing. They disagree, however, about whether Teva has met its burden of plausibly alleging or otherwise showing that it will suffer an actual and imminent injury that is fairly traceable to the Suboxone Letter Decision. Teva argues that “first applicant status” constitutes a property right “no different from a patent” and that the right exists “regardless of whether the exclusivity holder uses the right itself.” But court said that Teva’s theory of “embedded value” misconceives how the Hatch-Waxman Amendments and the MMA function and what Article III demands. Teva fails to identify any precedent that has ever held that a first applicant acquires a property interest akin to a patent as soon as it files a substantially complete ANDA containing a Paragraph IV certification and provides the requisite notice. Because first and foremost, a patent differs in fundamental respects from first applicant status. Nor is the Court convinced that a putative first applicant attains an alienable interest in its status immediately upon submitting its ANDA and effecting notice of the Paragraph IV certification. In sum, Teva has failed to “show that [it] ‘has sustained or is immediately in danger of sustaining some direct injury,’ as the result of the FDA’s Suboxone Letter Decision.

Future Loss of Right to Exclude:

Teva argues, in the alternative, that it will likely suffer a concrete injury in the near future if the Suboxone Letter Decision is allowed to stand and that this imminent harm is sufficient to sustain its standing to sue. It asserts, in particular, that it will suffer “tens of millions of dollars in lost sales due to the decreased market share it will have when [the] FDA unlawfully approves its competitors during what Teva alleges to be its legally-protected exclusivity period.” Court said that the cases cited by Teva are not controlling for present purposes. Teva will, accordingly, have the right—if it is a bona fide first applicant—to challenge a decision by the FDA permitting one its competitors (other than another first applicant) to proceed to market even before Teva’s ANDA is approved. Although the presence of tentative approval was not a sine qua non of Teva’s standing in that case, it was essential to the court’s finding that Teva’s alleged injury was certain and impending. Because there is no guarantee that the FDA will approve any of the existing ANDAs. Without tentative approval as a signal or any other indication about the status of the FDA’s review, the Court has no means of assessing whether any ANDA is likely to receive approval, and if so, when that is likely to occur. Moreover, even if the FDA eventually approves an ANDA for cyclosporine, the Court can only speculate about whether Teva’s ANDA will still be under review at that point. Most significantly, the FDCA includes six “forfeiture events” that result in a first applicant’s loss of “[t]he 180-day exclusivity period. The Court, accordingly, concludes that Teva’s asserted loss of exclusivity due to the FDA’s Suboxone Letter Decision fails to satisfy the causation and redressability requirements for Article III standing.

Court further said that Teva’s second claim to standing—that it was injured by the FDA’s failure to abide by the procedural requirements set forth in the APA—fares no better. Teva alleges that, because the FDA’s Suboxone Letter Decision “adopted precisely the opposite position from the one taken in its MMA regulations,” the FDA was required to (and did not) engage in notice-and-comment rulemaking. The Supreme Court, however, has held that the allegation of “a bare procedural violation, divorced of any concrete harm,” does not “satisfy the injury-in-fact requirement of Article III.” Here, the “essential injury” to Teva’s “own interest” is the potential loss of exclusivity. And, as explained above, the Court has concluded that the “chain of causation” between the FDA’s Suboxone Letter Decision and Teva’s alleged loss of exclusivity “is speculative at best.” The Court, accordingly, holds that Teva’s asserted procedural injury also fails to satisfy the constitutional minimum for standing to sue.