Tuesday, October 6, 2020

Everolimus - USA


IPR decision: Oct. 05, 2020

AIA Review #

Filing Date

Institution Date




Final Written Decision




Par Pharmaceutical, Inc*.


Novartis AG

Challenged   claims patentable

*This proceeding as initially filed named Par Pharmaceutical, Inc. as the sole Petitioner. Argentum Pharmaceutical LLC was joined as a party to this proceeding via a Motion for Joinder in IPR2017-01063; West-Ward Pharmaceuticals International Limited was joined as a party via a Motion for Joinder in IPR2017-01078. Subsequently, Par and West-Ward separately requested termination of their participation in the proceeding pursuant to settlement. Argentum Pharmaceutical LLC is the sole remaining Petitioner.

US 9,006,224 (Novartis AG; Exp: 07/01/2028)

1. A method for treating pancreatic neuroendocrine tumors, comprising administering to a human subject in need thereof a therapeutically effective amount of 40-O-(2-hydroxyethyl)-rapamycin as a monotherapy and wherein the tumors are advanced tumors after failure of cytotoxic chemotherapy.

Saturday, October 3, 2020

Carvedilol – USA


On Oct 02, 2020, Federal Circuit vacated district court’s grant of JMOL and reinstated the jury verdicts of infringement and damages.

Background of the case:

Glaxo owns US 5,760,069 patent which claims treatment with a combination of carvedilol and one or more of an angiotensin-converting enzyme (“ACE”) inhibitor, a diuretic, and digoxin. GSK on Nov. 25, 2003 filed reissue application for ’069 patent, which ultimately issued as US RE40,000 on Jan. 8, 2008. This patent expired on June 7, 2015. Glaxo own another patent, US 4,503,067 which claims carvedilol and related compounds. This patent expired on March 5, 2007. Both these patents were listed in Orange Book (OB) for drug, Coreg®. USFDA initially approved carvedilol in Sep 1995. In May 1997, the FDA approved carvedilol for the additional treatment of congestive heart failure. In March 2002, Teva filed ANDA with PIII certification to US’067 patent & P-IV certification to US’069 patent. Glaxo did not sue Teva based on any of OB listed patents. Teva received FDA “tentative approval” for its ANDA in 2004. Teva, on June 9, 2004, issued a press release to this effect mentioning among other things that its product is “AB rated” to Coreg®. On expiration of the ’067 patent in 2007, Teva launched its generic carvedilol tablet. Teva’s label dated “8/2007” mentioned 2 indications:

1. Left Ventricular Dysfunction following Myocardial Infarction(MILVD)… 

2. Hypertension…

Before this final approval, Teva carved out third indication ie. Congestive Heart Failure. Thus, in September 2007, when the FDA finally approved Teva’s ANDA as an AB-rated version of GSK’s Coreg®, Teva’s skinny label was only indicated for hypertension and post-MI LVD—neither of which was covered by any patent.

Both Teva and the FDA announced the approval of generic carvedilol with a press release. Teva also announced that it would immediately begin shipping its product but did not suggest that its product should be used to treat CHF. In 2011 the FDA required Teva to amend its carvedilol label to include CHF indication. Teva, thus, amended its label to include the indication for treatment of heart failure, as required by the FDA. On July 3, 2014, GSK filed suit for induced infringement of the RE’000 patent. Jury trial was initiated. Teva presented the defenses of patent invalidity and non-infringement. Teva argued that since it had omitted (“carved out”) CHF indication from its initial 2007 label till Apr. 2011 (Skinny period) Teva could not be found to induce prescribing physicians to infringe the ’000 patent. Teva also argued that it could not be found to induce prescribing physicians to infringe the ’000 patent between May 2011 (when it amended label to include CHF) to June 2015 when patent expired (full label period).

The jury found that Teva induced infringement of claims 1–3 during the period starting January 8, 2008 to April 30, 2011 (Skinny period); and that Teva induced infringement of claims 1–3 and 6–9 during the amended label period starting May 1, 2011 and ending June 7, 2015 (full label period). The jury assessed damages based on a combination of lost profits and royalty, and found that the infringement was willful. The district court granted Teva’s motion for JMOL (judgment as matter of law), stating that the verdict of induced infringement was not supported by substantial evidence because “GSK failed to prove by a preponderance of the evidence that ‘Teva’s alleged inducement. The district court explained that: “Without proof of causation, which is an essential element of GSK’s action, a finding of inducement cannot stand.” The court stated that “even in Sep. 2007, when generic companies (including Teva) began selling carvedilol, doctors relied on guidelines and research, as well as their own experience, in addition to GSK marketing.” Therefore, a reasonable fact-finder could only have found that these alternative, non-Teva factors were what caused the doctors to prescribe generic carvedilol for an infringing use & not Teva. GSK appealed.           

Federal Circuit analysis:

Glaxo argued that Teva’s marketing of carvedilol with knowledge and intent of its infringing use, and promotion of its generic product as the same as Coreg®, meet the legal requirements of active inducement of infringement.  Teva responds that the district court correctly ruled that Teva could not be liable for inducing infringement, because cardiologists already knew of carvedilol and its uses, and Teva did not directly “cause” them to infringe. Federal Circuit said that there was substantial evidence to support the jury’s verdict of inducement to infringe the ’000 patent. The jury received evidence that Teva’s promotional materials referred to Teva’s carvedilol tablets as “AB rated” equivalents of the Coreg® tablets. This means Teva’s product can be substituted for Coreg® & since, Coreg is approved for CHF indication, Teva’s label would induce physician to prescribe for CHF indication. GSK’s witness, Dr. McCullough, testified that doctors are “completely reliant” on information provided by the generic producers, and that doctors receive Teva’s product catalogs, visit its website, and read its product guides. Dr. McCullough told the jury that the press release of Teva “indicates that we should be able to prescribe generic carvedilol for heart failure”. Dr. McCullough testified that Teva’s Spring 2008 catalog lists Teva’s carvedilol tablets next to Coreg® tablets and uses the phrase “AB rating,” and that this would lead a doctor to believe that “they’re therapeutically interchangeable.”

There was ample record evidence of promotional materials, press releases, product catalogs, the FDA labels, and testimony of witnesses from both sides, to support the jury verdict of inducement to infringe the designated claims for the period of the ’000 reissue patent. The district court, thus, applied an incorrect legal standard for granting JMOL to Teva. Federal Circuit, therefore, reversed the grant of JMOL & remanded for entry of judgment on the verdict.

Dissent form Chief Judge Prost:

Judge Prost said that this case is about whether Teva induced infringement of GSK’s reissue patent, RE40,000, by marketing its generic carvedilol of for unpatented uses through a “skinny label” & “full label” period.

With respect to skinny label, Judge Prost said that Congress provided for skinny labels for exactly these circumstances, such that the lone method covered in the ’000 patent would not foreclose access to more affordable carvedilol. Here, the Majority undermines Congress’s provision for skinny labels by substantially nullifying section viii. Teva in this acted exactly as Congress intended. Teva waited until GSK’s patent covering the carvedilol compound expired to launch its product covering two unpatented indications—hypertension and post-MI LVD. So, when GSK’s ’000 reissue patent later issued—reciting a narrow method of treating a third indication, CHF—Teva’s skinny label did not even suggest using its product according to the patented method. In marketing its generic carvedilol, Teva never stated that it was approved, or could be used, to treat CHF. Moreover, the parties agreed that when Teva launched, its skinny label did not instruct doctors to prescribe generic carvedilol to treat CHF. Also, GSK failed to present evidence showing that doctors relied on the label in making prescribing decisions. District court was right when it granted JMOL in favour of Teva a because “neither sufficient nor substantial evidence supports the jury’s finding of inducement.”

With respect to full label, Judge Prost said that at the FDA’s direction, Teva amended its label years later to include the patented method, but there was still no inducement via the full label. Nothing changed in the market, and doctors’ prescribing decisions were not affected. GSK failed to prove causation during the full label period. No evidence suggests that any affirmative act by Teva actually caused doctors to directly infringe the patented method. Specifically, no evidence suggests that doctors relied on Teva’s full label in making their prescribing decisions. The record also demonstrated that many generic carvedilol sales occurred without the doctors’ knowledge at all. In sum, to the extent the doctors prescribed generic carvedilol to treat patients according to the claimed method, no evidence shows that they did so because of any action taken by Teva. The district court’s JMOL of noninfringement during the full label period should therefore be affirmed.

Judge Post further said…”Teva did everything right—using a skinny label, taking care not to encourage infringing uses—and yet, given today’s result, it was ultimately more costly for Teva to sell an unpatented drug for unpatented uses than it would have been to stay out of the market altogether: Teva only sold $74 million worth of carvedilol during the allegedly infringing period (mostly for unpatented uses) but now owes $234 million in damages for sales made for a single indication. This irony reflects the fact that Teva’s product was dramatically less expensive—costing less than 4 cents per pill as compared with Coreg®’s price of at least $1.50 per pill. Teva should not be liable for inducement”.

Friday, October 2, 2020

Ceritinib – India

On Sep 29, 2020, Intellectual Property Appellate Board (IPAB) set aside the order of Learned Controller finding compound patent invalid.

Brief background of the case is like this. Appellant, Novartis filed patent application - IN 3951/DELNP/2009 on Jun. 16, 2009. This application claims compound, Ceritinib as tyrosine kinase receptor inhibitor. This application was granted as IN 276062 on Sep 28, 2016. Post grant opposition was filed by Natco Ltd. on Sep 26, 2017. Patentee & opponent then filed their respective written submissions.  Hearing was rescheduled few times & finally it was held on Apr. 09-10, 2019. During this period additional documents were also filed after the announcement of date of hearing. Parties filed post hearing submissions & on Aug. 16, 2019, the Learned Controller by its order revoked the patent under lack of novelty, inventive step, section 3(d) & lack of sufficiency.

Appellant filed appeal to IPAB on violation of principle of natural justice. IPAB came heavily on the reasoning of Learned Controller & found that Learned Controller did not follow the proper procedure of law. IPAB said that the Learned Controller disregarded the recommendation of the Opposition Board which found patent valid. Second, the Learned Controller considered the evidence filed by the Opponent in relation to patent term extension and orange book listing but has disregarded the rebuttal evidence filed by the Appellant. Third, the Learned Controller has failed to consider the arguments on novelty given by the Appellant and has also failed to rely upon the expert affidavit submitted along with it.

With respect to novelty, IPAB said that the entire finding of invalidity is based without any prior art cited which discloses or exemplifies Ceritinib, the compound subject matter of IN 276026. The Controller has engaged in prohibited act of “cherry picking” of the constituents, substituents, their arrangement, their positioning, their linkage and interplay from the subject patent IN 276026 and tried to locate them in the vast pool of possible substituents contained in markush claims of prior art citations. It is also settled practice that in order to demonstrate lack of novelty, the anticipatory disclosure must be entirely contained within a single document. However, if a cited document refers to a disclosure in another document in such a way as to indicate that, that disclosure is intended to be included in that of the cited document, then the two are read together as though they were a single document. Here, Learned Controller took help of two cited prior arts to attack “novelty’ of the subject patent by picking suitable equivalent substitutions, keeping inventive structure of the subject patent IN’026 in sight.

IPAB also said that the opposition was filed by M/s Natco Pharma Limited on 26/09/2017. At the time of filing of opposition, opponent paid fees as a natural person. So, filing the opposition by a legal entity and paying the prescribed fee of filing opposition with the fee which is applicable to natural person (INR 2400) is not justifiable. If the balance fee of (INR 9600) was paid on 08/11/2017 – a date much later than the last date of filing opposition, the opposition was not maintainable as per the provisions of the Patents Act and the Rules made there under. The post-grant opposition was not maintainable ab initio for lack of filing proper prescribed fee.

IPAB finally found that the impugned order is void of merit & thus set aside the order. 

Ibrutinib - India


On Sep 29, 2020, Intellectual Property Appellate Board (IPAB) set aside the order of Learned Controller finding compound patent invalid.

Brief background of the case is like this. Appellant, Pharmacyclics Inc. filed patent application - IN 1642/DELNP/2009 on Mar. 12, 2009. This application claims compound, Ibrutinib as Bruton Tyrosine Kinase inhibitor. This application was granted as IN 262968 on Oct 03, 2014. Post grant opposition was filed by Laurus labs on Sep. 24, 2015. Patentee & opponent then filed their respective written submissions.  Hearing was rescheduled few times & finally it was held on Nov 22, 2019. During this period additional  documents were also filed after the announcement of date of hearing. Parties filed post hearing submissions & on Mar 04, 2020, the Learned Controller by its order revoked the patent under lack of inventive step.

Appellant filed appeal to IPAB on many grounds under procedural & technical aspects. IPAB come heavily on these two aspects & found that Learned Controller did not follow the proper procedure of law. IPAB citing the judgment of High Court (W.P.(C) No. 12105/2019; decided on 20/11/2019) provided important pointers while dealing with the post grant opposition.

Let’s see the IPAB findings in summary:

Technical aspects (Inventive step)

1The prior arts should be analogus to the claimed invention.

[The prior art relied upon by the opponent pertains to LCK inhibitors, whereas, the invention pertains to BTK inhibitors.]

2. Reasoning of substitution of one group by another group should be justified properly.

[Here, IPAB said that Learned Controller made not only legal error but also scientific errors when deciding the issue of inventive step which is neither based on the arguments of the Appellant/Respondent, written submissions or the evidence filed by their experts.]

3. There should be proper motivation to combine the references.

[IPAB said that Motivation to attach a Michael acceptor from prior art to hypothetical compound has not even referred in the impugned order.]

4. There should not be any hindsight analysis in inventive step inquiry.

[IPAB said that the substitutions are somehow trying to trace back to the invention by keeping the invention in forefront and it amounts to “hindsight analysis”.]

Procedural aspects:

1. Trend of filing additional evidences under Rule 60 after the hearing being fixed by the Controller or place documents having evidentiary value in guise of “publication” under Rule 62(4).

[IPAB said that these actions do not find proper basis in the Rules and need to be addressed so as to smoothen the process of post–grant oppositions and reduced the timelines being consumed unduly. It should be ensured that the provisions of Rules 60 and 62 should be followed strictly.]

2. Learned Controller should provide reasons for his findings.

[IPAB said that it is well within his powers as provided in the law to disagree with the opinion of the opposition Board, but while he disagreed on this ground should have annotated the reasons thereof properly.]

3. Inventive step is mixed question of law & facts.

[Here, Learned Controller ignored the legal aspects from the determination of the “inventive step” & focused only on factual aspects.]

4. There is no concept of “ordinary” person skilled in the art in the Indian Patent Act, 1970.

[IPAB said that the determination of “inventive step” as envisaged in the Patents Act under section 2(1)(ja) clearly stipulates “person skilled in the art” & not “ordinary” person skilled in the art. Therefore, inquiry should be made in view of the person skilled in the art when dealing with inventive step attack.]

IPAB, therefore, set aside the impugned order of the Learned Controller.

Wednesday, September 30, 2020

Ezetimibe & Simvastatin – France


On Sep 25, 2020, Court of appeal of Paris found SPC for combination of ezetimibe & simvastatin product invalid.


Merck owns European Patent No. 0720599 (EP 599) entitled "Hydroxy-substituted azetidinone compounds effective as hypocholesterolemic agent” which is expired on September 14, 2014. It claims novel compound ie. Ezetimibe and also combination with other agents such as cholesterol biosynthesis inhibitor for the treatment of atherosclerosis. Specifically, dependent claims 9 to 18 claim the combination which cover simvastatin among other inhibitors. Merck granted first SPC (n°03C0028 – expired on April 17, 2018) on this basic patent which covers single ezetimibe product, EZETROL.  Merck also obtained second SPC (n°05C0040 – expired on April 2, 2019) on the same patent which covers ezetimibe & simvastatin combination product, INEGY.

Teva launched generic version of EZETROL  on April 18, 2018 and of INEGY on April 24, 2018 & requested invalidity of claims 9 to 18 of EP’599 patent and of the SPC No. 040 before court. Tribunal de Grande Instance of Paris court rejected Teva’s request & ordered Teva to pay the cost and to pay Merck the sum of 100,000 euros. Teva appealed.

Appeal courts analysis:

Article 3 of Regulation (EC) No 469/2009: SPC shall be granted if –

(a) the product is protected by a basic patent in force;

(b) a valid authorisation to place the product on the market as a medicinal product has been granted in accordance with Directive 2001/83/EC or Directive 2001/82/EC, as appropriate;

(c) the product has not already been the subject of a certificate;

(d) the authorisation referred to in point (b) is the first authorisation to place the product on the market as a medicinal product.

Court said that aforementioned articles of the Regulation must be interpreted in the light of the case law of the CJEU, in particular with regard to the Sanofi C 443/12 (Irbesartan + HCTZ) decision dated December 12, 2013, which deals with similar facts. Merck argued that this Sanofi case law is not applicable to the case at hand in that the product in question concerned the combination of irbesartan with HCTZ (hydrochlorothiazide) and that the patent did not contain a claim expressly mentioning HCTZ.  Here, in present case, claim 17 specifically mentions simvastatin and thus it is protected. The Court said that the CJEU, in its Sanofi decision, held that even if the condition laid down in Article 3(a) of Regulation No 469/2009 were satisfied, for the purpose of the application of Article 3(c) of that regulation, it cannot be accepted that the holder of a basic patent in force may obtain a new SPC, each time he places a product on the market. Court further said that Person skilled in the art after reading the patent specification would not assume this combination as “distinct product”. The description of the patent, which uses the singular to designate the invention, and uses the formula "in yet another aspect" to present the combination of a hydroxy-substituted azetidinone, object of the invention, with a cholesterol biosynthesis inhibitor, refers indifferently for hydroxy-substituted azetidinones alone and for their combination with a cholesterol biosynthesis inhibitor.

In the present proceeding, as in the Sanofi case, the EP 599 patent protecting the active ingredient in particular ezetimibe, has already led to the grant of a SPC on this active ingredient to its holder, and this first SPC relating to ezetimibe alone allowed Merck to oppose to the marketing of a drug containing ezetimibe in combination with a statin such as simvastatin and having a therapeutic indication similar to that of the drug Ezetrol. Thus, the supplementary protection certificate FR05C0040 is null and void.

Parallel proceedings related to this SPC:

France: On Feb 14, 2020 this appellate court reversed the decision of preliminary injunction granted against Sandoz & Mylan.

Norway: On December 21, 2018, Borgarting Court of Appeals affirmed lower court decision which granted preliminary injunction.

Czech Republic: On August 28, 2018, Prague Court of Justice issued preliminary injunction.

Portugal: On September 7, 2018, Portuguese Arbitral Tribunal issued preliminary injunction.

Belgium: On December 21, 2018, Commercial Court of Brussels issued preliminary injunction.

Austria: On July 10, 2019, Vienna Court of Appeals affirmed preliminary injunction.

Netherlands:  On October 23, 2018, Court of Appeal of The Hague affirmed & held SPC invalid.

Germany:  On March 15, 2019, Court of Appeal of Düsseldorf affirmed & held SPC invalid.

Spain:  On September 12, 2018, Regional Court of Barcelona found SPC invalid.

Monday, September 28, 2020

Ibrutinib - USA


IPR decision: Sep. 24, 2020


AIA Review #

Filing Date

Institution Date




Final Written Decision






Sandoz Inc.


Pharmacyclics Inc.

Some Challenged Claims Unpatentable

US 9,795,604 (Pharmacyclics LLC; Exp: 10/24/2034

1. A method of treating chronic graft versus host disease (GVHD) comprising administering to a patient having chronic GVHD a therapeutically effective amount of a compound of the structure: (Ibrutinib) thereby treating the chronic GVHD in the patient. 

54. A method of treating chronic graft versus host disease (GVHD) comprising administering to a patient having chronic GVHD from 140 mg/day to 840 mg/day of a compound of the structure: (Ibrutinib)

55. A method of treating chronic graft versus host disease (GVHD) comprising administering to a patient having chronic GVHD about 420 mg/day of a compound of the structure: (Ibrutinib)


PTAB decision summary:

PTAB found claims 1, 6–10, 24, 35, 39, 55 unpatentable & claims 4, 13, 15, 28–31, 43–46, 50–53 patentable. Petitioner primarily relied on US 2015/0140085 reference which disclosed ibrutinib, treatment of GVHD, dose range & administration part. PTAB found that US’085 anticipated those claims (1, 6–10, 24, 35, 39, and 55). With respect to other claims which PTAB found patentable were related to treatment of cGVHD where patients received prior steroid therapy. PTAB held that the field was not fully developed with respect to treatment of steroid refractory/resistant cGVHD. PTAB said that given the poor understanding of cGVHD, the lack of animal models and standardized measurement criteria, and the unpredictability in the field, it is not surprising that many potential treatments have proven unsuccessful. Therefore, POSA would not have reasonable expectation of success in treating steroid resistant/refractory cGVHD. Other prior arts also do not cure this deficiency. Thus, claims 4, 13, 15, 28–31, 43–46, 50–53 are not shown to be unpatentable.



Saturday, September 19, 2020

Weekly Patent Litigation Round-Up


Delaware judge deals Biogen another blow in Tecfidera patent fight

A federal judge in Delaware on Wednesday dealt another setback to drug company Biogen Inc in its effort to keep generic versions of its multiple sclerosis treatment Tecfidera off the market through patent litigation. Handing a win to Novartis AG unit Sandoz and other generic drug companies, U.S. District Judge Maryellen Noreika said a Biogen patent on a Tecfidera dosing regimen was invalid because it did not sufficiently describe the claimed invention...



Mylan and Development Partner, Synthon, Win Significant European Patent Office Ruling Related to Copaxone® 40mg/mL

HERTFORDSHIRE, England and PITTSBURGH, Sept. 15, 2020 /PRNewswire/ --Mylan N.V. (NASDAQ: MYL) today announced that the Technical Board of Appeal of the European Patent Office (EPO) has held that Yeda Research and Development Company, Ltd.'s European Patent no. 2 949 335 related to Teva's Copaxone® 40 mg/mL three times weekly product is invalid and revoked across Europe. With the EPO's decision, Mylan has once again overcome Teva's attempts to restrict MS patients' access to safe and affordable alternatives. Over the course of the last eleven years, Mylan has successfully defeated Teva's four waves of U.S. patent litigation, eight Citizen Petitions, injunction proceedings in India, and more than 15 regulatory challenges, patent litigations or commercial actions across Europe. The EPO's positive ruling will allow Mylan to immediately return to the market and accelerate commercialization in other markets across Europe...



Fresenius Faces French Damages Over Alimta

Fresenius Kabi must pay Eli Lilly €28m in damages after a French court of first instance found that the generics firm’s pemetrexed infringed intellectual property protecting the Alimta chemotherapy brand. The German firm has commented on possible next steps..



IPAB allowed an appeal and granted a patent to pfizer for tofacitinib and its salts

The IPAB  allowed  an appeal and granted a patent to Pfizer for Tofacitinib and its salts (application 991/MUMNP/2003. This application claimed the compound 3-{(3R, 4R)-4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-3-oxo-propionitrile and pharmaceutically acceptable salts thereof (Tofacitinib and its salts) and was refused by the patent office on various grounds, including anticipation by prior claiming and section 3(d). The main prior art cited by the controller for novelty was Document WO 0142246(D1) that claimed and disclosed the compound 3-(4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl)-3-oxo- propionitrile. The ground of anticipation by prior claiming was not raised in the hearing notice and for section 3(d) no known substance was identified.



Ibrutinib Patent Revocation: IPAB Says the Stay is Here to Stay

Latest in the Ibrutinib patent saga is IPAB’s order maintaining the interim stay over the revocation of the anti-cancer drug patent. This comes at an interesting time, as a recent report by I-MAK suggests that US-based Biopharma Company AbbVie might be attempting to build a patent wall around Imbruvica (Ibrutinib’s market brand), having secured 88 patents out of 165 applications filed. Imbruvica currently generates a whopping $4.5 billion a year for AbbVie. In India, Pharmacyclics LLC (owned by AbbVie) had been granted the patent in 2014 (IN 262968), against which Laurus Labs had filed a post-grant opposition under Section 25(2) of the Patents Act, 1970 the next year. The hearing was scheduled in November 2017, but was adjourned and rescheduled to 25th September 2019, before being ultimately held on 22nd November. Consequently, the patent was revoked on grounds of lack of inventive step in March 2020.…



Dr Reddy’s announces settlement of Revlimid capsules patent litigation with Celgene in US

Dr Reddy’s Laboratories announced the settlement of their litigation with Celgene, a wholly-owned subsidiary of Bristol Myers Squibb relating to patents for REVLIMID (lenalidomide) capsules. In settlement of all outstanding claims in the litigation, Celgene has agreed to provide Dr Reddy’s with a license to sell volume-limited amounts of generic lenalidomide capsules in the US beginning on a confidential date after March 2022 subject to regulatory approval. The agreed-upon percentages are confidential. Dr Reddy’s is also licensed to sell generic lenalidomide capsules in the US without volume limitation beginning on January 31, 2026.…


Thursday, September 17, 2020

Dimethyl fumarate - USA

On Sep. 16, 2020, Delaware Court found multiple sclerosis method of use patent invalid for lack of written description support under principles of collateral estoppel.

Plaintiffs (Biogen) sued many generic companies based on their filing of ANDAs seeking to market generic versions of Tecfidera®. This product is indicated for relapsing forms of Multiple Sclerosis (MS). The patent at issue here is U.S. Patent No. 8,399,514, relates to method of treatment of MS with 480 mg dose. Plaintiff sued all ANDA filers in Delaware court, except Mylan - sued in district court of West Virginia. Both the proceedings carried out on almost similar timelines.  On June 18, 2020, West Virginia court found that Mylan had proven by clear and convincing evidence that the Asserted Claims of the ’514 Patent are invalid for lack of written description. You can read the decision summary “here on this blog”.

The issue now before Delaware court was whether the judgment of invalidity rendered in the Mylan case should apply here under the principles of collateral estoppel. Delaware Court evaluated the collateral estoppel factors under Third Circuit law: (1) the identical issue was previously adjudicated, (2) that issue was actually litigated, (3) the previous determination was necessary to the decision and (4) the party being precluded from relitigating the issue was fully represented in the prior action.

Delaware court heard all the parties and weighing these factors ultimately found that collateral estoppel applies here. Thus, claims are invalid for lack of written description support.

Thursday, September 10, 2020

Estradiol - USA


On Sep 02, 2020, Delaware Court found estrogen transdermal patents invalid under lack of enablement & lack of written description support.

Noven pharmaceuticals (Plaintiff) sued Amneal pharmaceuticals (Defendant) under Hatch-Waxman Act as Defendant filed ANDA to market generic version of Minivelle®. Noven markets Minivelle® transdermal film in USA for the treatment of moderate to severe vasomotor symptoms due to menopause.  Noven sued Amneal for the infringement of US 9,833,419; US 9,730,900 and US 9,724,310 patents which are expiring in July 2028. Amneal countered with non-infringement, invalidity based on enablement, written description support & on-sale bar defenses. Court held bench trial in Nov. 2019 & Jan. 2020.

Claim 1 of US’419 is representative:

1. A monolithic transdermal drug delivery system for estradiol, consisting of (i) a backing layer, (ii) a single adhesive polymer matrix layer defining an active surface area and, optionally, (iii) a release liner, wherein the single adhesive polymer matrix layer comprises an adhesive polymer matrix comprising estradiol as the only drug, wherein the adhesive polymer matrix layer has a coat weight of greater than 10 mg/cm2 and includes greater than 0.156 mg/cm2 estradiol, and the system achieves an estradiol flux of from 0.0125 to about 0.05 mg/cm2/day, based on the active surface area.

Claim 1 of US’900 is representative for US’900 & US’310 evaluation :

1. A method for administering estradiol, comprising applying to the skin or mucosa of a subject in need thereof a monolithic transdermal drug delivery system consisting of (i) a backing layer and (ii) a single adhesive polymer matrix layer defining an active surface area and comprising an adhesive polymer matrix comprising estradiol as the only drug, wherein the polymer matrix has a coat weight of greater than about 10 mg/ cm2 and includes greater than 0.156 mg/ cm2 estradiol, and the system achieves an estradiol flux of from about 0.0125 to about 0.05 mg/ cm2 /day, based on the active surface area.



Infringement of US’419 patent:

Noven contented that Amneal infringed claims of US’419 patent under literal infringement. Specifically Noven argued that Amneal’s ANDA product meet the limitation of “coat weight of greater than 10 mg/cm2".” During claim construction court construed this limitation as having plain & ordinary meaning. Amneal ANDA product have inprocess coat weights above 10 mg/cm2. Specifically, the upper limits of the coat weight in the tentatively-approved product are 10.75 mg/cm2 for any individual coat weight value and 10.5 mg/cm2 for the average coat weight value. Similarly, the upper limits under Anmeal's proposed amended ANDA for individual and average coat weights are 10.45 and 10.40 mg/cm2, respectively (Amneal amended its ANDA after tentative approval to tighten the limits). Court, thus held that Anmeal's product infringes the asserted claims of the '419 patent.

Infringement of US’900 & US’310 patents:

Noven contented that Amneal infringed claims of US’900 & US’310 patents under Doctrine of Equivalents (DOE). Specifically Noven argued that Amneal’s ANDA product meet the limitation of “coat weight of greater than about 10 mg/cm2".” During claim construction court construed this limitation as - "having a coat weight which weighs more than 110% of 10 mg/cm2"; that is, a coat weight of more than 11 mg/cm2. Because the claim mentions “about” term which is defined in the specification as plus or minus 10%. Court sided with Amneal during claim construction which proposed claim construction as - 9 mg/cm2 to 11 mg/cm2.  Amneal argued that lower limit is excluded since specification mentions this lower limit with respect to the prior formulation of Noven, Vivelle-Dot®. Therefore, infringement would be found only if Amneal’s ANDA contains coat weight of greater than 11 mg/cm2. As seen in infringement of US’419 patent, Amneal product contains coat weight less than 11 mg/cm2. Thus, Amneal does not infringe under literal infringement.

Noven argued that Amneal product infringes claims under DOE. Amneal counterargued that DOE theory is barred because of prosecution history estoppel (PHE). Specifically, Amneal argued that during prosecution Noven added this coat weight limitation & thus there is an estoppel. The Court agreed with Amneal & said that the amendments to add the coat weight limitations were narrowing. Secondly, the reason for the amendment is "a substantial one relating to patentability ." The purpose of the amendment was to avoid an obviousness rejection based on prior arts and highlight the "unexpected results based on the coat weight of the polymer to achieve the claimed flux of drug delivery." Third, Noven has not rebutted the presumption that estoppel applies, because it has failed to show that the coat weight amendment is "tangential to the asserted equivalent in the Amneal ANDA Product." Court did not find Noven’s argument persuasive. Noven argued that prior art references disclosed a coat weight range of 9 to 11 mg/cm2 , so the Examiner could not have relied on the coat weight amendment to overcome rejection. Noven further argued that the Examiner had initially rejected all claims, including claim 27, which included the limitation "a coat weight of greater than about 10 mg/cm2”. Noven said that it later added this limitation into claim 1 & thus this limitation is not distinguishing feature that is responsible for allowance of claims. But court agreed with Amneal instead & said that without the coat weight limitation in the claims, Noven "would not have been able to argue that the claimed invention embodied the 'unexpected result' of higher coat weight causing higher flux rates, to overcome the obviousness rejection."

Court, therefore held that, Noven failed to prove that Amneal's ANDA product infringes the asserted claims of the '900 or '310 patents under the doctrine of equivalents.



Specification defines “transdermal” as delivery, administration or application of a drug by means of direct contact with skin or mucosa. As used herein, "dermal" includes skin and mucosa, which includes oral, buccal, nasal, rectal and vaginal mucosa.

Lack of enablement:

With respect to Lack of enablement, Amneal argued that asserted patents fail to enable the claimed transmucosal estradiol patch systems. The specification only teaches about transdermal system containing skin & not mucosa. The asserted claims are broad; they cover not just estradiol patch systems for application to the skin but also estradiol patches to be applied to any mucosal tissue, including oral, buccal, nasal, rectal, and vaginal tissue. Specification fails as to how to make or use an estradiol patch system on any mucosa (let alone all mucosae ). The specification is silent as to how much estradiol to include, or what coat weight should be used. The specification fails to identify which excipients or ingredients would be useful for making any (let alone all) of the claimed transmucosal systems. Moreover, there is no mention in the specification of whether or how the central discovery of the patents - increasing coat weight to increase flux - would apply to the various mucosae. This is perhaps not surprising, since the relationship was discovered by testing flux across skin, not mucosa! tissue. The specification's example with respect to the flux achieved with various formulations pertained only to skin, not mucosae. A POSA seeking to make a claimed transmucosal embodiment would have faced the added challenge of obtaining the claimed flux values while keeping the estradiol concentration in the claimed range and the coat weight in the claimed range above 10 or 11 mg/cm2.

Dr. Lobo (Defendant expert) explained that the physiology and drug release characteristics of oral, buccal, nasal, rectal, and vaginal mucosa could vary greatly - not only from skin, but from one another. This is primarily because the skin has an impervious barrier due to a protective outer layer, known as the "stratum comeum," which is lacking in mucosae. Drug delivery across the skin is, therefore, constant and prolonged over days, while estradiol delivery across the mucosae was known to be rapid, sometimes exhibiting a burst effect. The patents provide a POSA no guidance about how to achieve the claimed daily flux when the drug is so rapidly absorbed over mucosa.

Court said that the patents and publications Noven relied on in an effort to show that the state of the art was sufficiently advanced that a POSA would somehow have found in the specification of the Patents-in-Suit sufficient guidance to make and use a transmucosal embodiment of the claims (let alone embodiments with respect to each mucosa covered by the claims) do not suffice. Turning to the quantity of experimentation, the "nature and predictability of the field," and the level of ordinary skill, the Court found that the development and use of transmucosal patch systems constituted novel, highly unpredictable endeavors at the pertinent time. Noven's remaining arguments for enablement are unavailing. Court therefore concluded that the Asserted Claims of the Patents-inSuit are invalid for lack of enablement.

Lack of written description support:

As argued above for enablement, Court said that the specification lacks any description or example of a transmucosal estradiol system, including any description or example of any oral, buccal, nasal, rectal, or vaginal patch systems, even though such systems are within the scope of the claims. Aside from the specification's definition of"flux" and "transdermal" the words "oral," "buccal," "nasal," "rectal," or "vaginal" mucosa do not appear in the specification. The specification fails to convey to a POSA the inventor's possession or invention of the claimed transmucosal estradiol patch systems. Transmucosal delivery and formulation is a separate and distinct scientific field from transdermal formulation, each with separate bodies of specialized knowledge and separate technical literature and treatises. Court thus held that a POSA reading the specification would not have understood the inventor of the patents-in-suit to be in possession of the transmucosal embodiments. Therefore, the Asserted Claims are invalid under lack of written description support.

Saturday, September 5, 2020

Vascepa® – USA

On Sep. 03, 2020, Federal Circuit affirmed (Rule-36 judgment) Nevada district court decision finding method of treating hypertriglyceridemia patents invalid as obvious.

This appeal was filed by Amarin (Plaintiff) against the decision of Nevada district court which held claims of US 8,293,728; US 8,318,715; US 8,357,677; US 8,367,652; US 8,431,560 and US 8,518,929 invalid in Hatch-Waxman litigation. District court found that defendants (Hikma & DRL) established by clear and convincing evidence at trial that all asserted claims are prima facie obvious. You can read the district court decision summary “reported here” on this blog.