Source: https://www.orangebookblog.com/2013/02/index.html
Timestamp: 2019-04-20 06:57:09+00:00

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In an opinion issued earlier this month, Defendants moved to dismiss for lack of subject matter jurisdiction with respect to one of two asserted patents in a lawsuit involving generic versions of EMEND (fosaprepitant dimeglumine) for injection.
Merck filed a supplement to its NDA to add a 150 mg dosage strength, listing two patents, U.S. Patent Nos. 5,591,336 and 5,716,942. Upon approval, however, only the '336 patent was listed in the Orange Book. Both patents were listed in the Orange Book for the previously approved 115 mg dosage strength. Defendants filed ANDAs for the 150 mg dosage strength only and made paragraph IV certifications for the '336 patent and not the '942 patent. Merck's complaint alleges infringement of both patents.
Judge Sheridan, relying on judicial efficiency and common sense, held that subject matter jurisdiction existed despite the fact that the '942 patent was not listed in the Orange Book. Defendants alleged the same defenses for both patents and could not dispute that the '942 patent claims the use of drugs that their ANDAs concern.
The court stated that 35 USC § 271(e)(2) does not suggest that "infringement actions against ANDA filers must be based only on Orange Book listed patents." Rather, the jurisdiction standard applied by Judge Sheridan (from AstraZeneca Pharm. LP v. Apotex Corp., 669 F.3d 1370, 1377 (Fed. Cir. 2012)) was that jurisdiction exists where "a patent owner alleges that another’s filing of an ANDA infringes its patent under § 271(e)(2)."
In Cephalon v. Watson, decided earlier this month, the Federal Circuit reversed a finding of invalidity for lack of enablement where the factual record of undue experimentation was insufficient. The patented invention involved methods of oral mucosal administration of fenatanyl with tablets including effervescent agents used as penetration enhancers. The effervescent agents evolve gas as a result of exposure to a soluble acid source. The district court's claim construction of "agent" required that the dosage forms of the soluble acid source and the effervescent agent be separate but co-administered.
At trial before Judge Robinson in the District of Delaware, Watson succeeded in proving the asserted patents (U.S. Pat. Nos. 6,200,604 and 6,974,590) were invalid for lack of enablement. Watson's expert witness provided testimony that co-administration would be "difficult" and "complicated." The district court found further support for those opinions in Cephalon’s expert testimony regarding the need for experimentation.
The Federal Circuit initially corrected the district court's determination that Watson's prima facie case of lack of enablement was not rebutted by Cephalon and stated that "there is no formal burden-shifting framework when addressing the issue of enablement." The court found that, despite the district court's credibility finding, the largely unsupported testimony of Watson's expert "carries little weight in this analysis." The court also found, contrary to the district court, that Cephalon's expert testimony regarding the need for routine experimentation did not support the unsubstantiated opinions of Watson's expert. Specifically, the Federal Circuit found that Watson failed to show how much experimentation would be required for co-administration and that such experimentation would be excessive, particularly where the specification provided at least some guidance.
Notably, Watson's expert witness did not specifically analyze the Wands factors at trial. However, the Federal Circuit explained that such an analysis was not required for Watson to carry its burden, and the record lacked evidence of undue experimentation even assuming the district court's cursory consideration of the Wands factors was accurate.
Despite the Federal Circuit's reversal of the invalidity holding, Watson still prevailed, as the Federal Circuit affirmed the district court's holding of noninfringement.
Following through on its plan announced earlier this month, Momenta Pharmaceuticals recently filed a petition for a writ of certiorari in Momenta v. Amphastar. As we reported previously, the Federal Circuit's decision in this case appears to conflict with its 2011 decision in Classen v. Biogen IDEC. Both cases concern the scope of the "safe harbor" under 35 U.S.C. 271(e)(1), which exempts certain activities that otherwise would amount to patent infringement.
Recapping briefly, in Classen, the patent owner accused its competitors of infringing patents claiming methods of immunization. Specifically, Classen alleged that the defendants' post-approval studies of vaccines were infringing activities, and the defendants argued that their participation in the vaccine studies was reasonably related to the FDA requirement to report adverse events to FDA, and was therefore encompassed by the safe harbor. In a 2-1 decision, the Federal Circuit found in favor of Classen, holding that 271(e)(1) "does not apply to information that may be routinely reported to the FDA, long after marketing approval has been obtained."
The defendants in Classen petitioned the Supreme Court, and the Court asked the Solicitor General to file a brief setting forth the views of the United States government. In its brief, the Solicitor General recommended that the Court deny review, stating that the case "would provide a poor vehicle for the Court to consider the application of Section 271(e)(1) to post-approval activities." On January 14, the Court denied cert in Classen, perhaps with an eye toward taking the Momenta case instead.
Whether the use of a patented invention in the course of post-approval manufacture of a drug for commercial sale, where the FDA requires that a record of that manufacturing activity be maintained, is exempted from liability for patent infringement under Section 271(e)(1) as "solely for uses reasonably related to the development and submission of information under a Federal law which regulates the manufacture, use, or sale of drugs."
Momenta asserts in its petition that the Federal Circuit's decisions in Classen and Momenta are irreconcilable, and that both are "fundamentally wrong." Momenta argues, for instance, that "[h]ad Classen been applied in this case, Amphastar's use of Momenta's patented invention would not have been exempted from infringement. Amphastar uses Momenta's patented method in the course of routine post-approval, commercial manufacturing of its drug, not to obtain pre-marketing approval." Momenta further argues that both Classen and Momenta are inconsistent with the statutory text and Supreme Court precedents, including the Court's most recent case interpreting the safe harbor, Merck v. Integra.
Finally, Momenta argues the scope of the safe harbor "is an issue of exceptional, immediate importance to the pharmaceutical industry." According to Momenta, "The Federal Circuit's diametrically opposed interpretations of Section 271(e)(1) have created immense uncertainty in a trillion-dollar industry that develops life-saving and life-enhancing drugs." Further, Momenta states, "the Federal Circuit's ruling in this case could shield from infringement any approved activity by a pharmaceutical company for which the company must maintain a record for possible future FDA inspection. This could render numerous method, composition, and packaging patents completely worthless."
Hat tip to Alex MacCormick for the news that Momenta filed its cert petition.
In Eurand v. Impax, decided last week by the Federal Circuit, a generic defendant, Impax, settled with the patent owner, Cephalon, and a settlement agreement provided for Impax's entry date into the market.
One of the entry date triggers occurred if Cephalon licensed or authorized a third party, not entitled to first-to-file exclusivity, to sell a generic--i.e., an authorized generic. Cephalon entered into a Sales Agent Agreement with Watson, which "appointed" Watson as a sales agent to "solicit" orders for Cephalon's generic version of AMRIX®, and required Watson to notify any potential customers that it was acting as Cephalon's sales agent. Under the agreement, Cephalon maintained the right to set the floor on prices, retained title to the generic drugs until they were transferred to the customer, and the generic products were to be sold solely under Cephalon's labeling and trademarks.
Impax argued that Watson was a licensed third party under the settlement agreement, thereby triggering Impax's early entry. The Federal Circuit rejected Impax's argument and confirmed that Watson was a mere sales agent and not a third party. Thus, no early entry was triggered.
Of particular interest here is that the parties' Settlement Agreement is publicly available. We have received a few requests for examples of settlement agreements in ANDA cases. Here is one.
This morning, February 19, 2013, the Supreme Court will hear argument in one of the most important patent cases in recent years-–Bowman v. Monsanto. The case specifically addresses patent exhaustion in the progeny of soybean seeds. But the Court’s opinion in this case could impact the protection of some of the most innovative biotechnology inventions in the country--including those relating to progenitive or self-replicating technologies. The opinion may also impact the viability of conditional sales of patented products. And it could alter U.S. patent law in a way that would have significant consequences for biotech firms and other institutions involved in biotech research and development.
This afternoon, a CLE-eligible panel discussion is being hosted by the American University Washington College of Law and the Federal Circuit Bar Association. The discussion will feature counsel for the parties and selected amici, and will be held at the American University Washington College of Law in Washington, DC. For the in-person discussion, attendees will be asked to take their seats at around 4:15 pm EST.
The panel discussion may also be seen live on the internet. The free webinar will be begin at 4:30 pm EST / 1:30 pm PST on the event website. No log-in will be required.
Scott P. McBride, a partner at McAndrews Held & Malloy and contributor to Orange Book Blog, will be one of the panelists. His team submitted an amicus brief on behalf of over twenty universities and university-related associations in the case, urging the Supreme Court to affirm the Federal Circuit's decision in favor of of the patent owner, Monsanto.
For additional information about the case and panel discussion, please visit the event website.
CPhI will be holding its 2nd annual Pharma IPR India conference in Mumbai on April 10-12. This was an outstanding conference last year, and it promises to be even better this year.
Pharma IPR India 2013 will take place over three days, focusing the first day on pharmaceutical intellectual-property rights in the United States, Canada, Brazil, and Mexico; the second day on Europe, Japan, and Australia; and the third day on India, China, South Africa, Russia, and Southeast Asia.
An early-bird registration rate is available through February 15th. In addition, save an extra 10% by mentioning Orange Book Blog.
Today, in the District of Delaware, Judge Burke issued a 171-page opinion holding that claim 8 of U.S. Patent No. 5,206,244, covering the entecavir molecule, is invalid as obvious. Entecavir is the active ingredient in Baraclude tablets, which are indicated for the treatment of chronic hepatitis B virus (HBV) infection. The 30-month stay of final approval of Teva's ANDA was set to expire tomorrow.
Judge Burke devoted 140 pages of his opinion to findings and conclusions that entecavir would have been obvious in light of the prior art. The court held that "the prior art clearly would have directed the skilled artisan to select 2'-CDG, a carbocyclic analog, as a lead compound for further development efforts," finding that "in direct contrast to BMS's arguments in its briefing, the testimony of its own expert at trial repeatedly and conclusively established that researchers were, in fact, treating and using 2'-CDG as a lead compound in the relevant time period." Similarly, in holding that a person of ordinary skill would have had a reason to modify 2'-CDG by adding a carbon atom at the 5' position, the court found "that the powerful admissions by BMS's expert severely undercut BMS's arguments to the contrary regarding motivation to combine." The court likewise found BMS's arguments regarding reasonable expectation of success unpersuasive, stating, "notably, BMS's opening brief fails to address this factor of the prima facie case in any great detail."
Before concluding that claim 8 of the '244 patent is invalid as obvious, the court examined the objective evidence of nonobviousness, observing that "all evidence relevant to obviousness or nonobviousness [must] be considered, and be considered collectively." First, the court, "following the direction of the Federal Circuit and this Court's case law, [found] that Teva's choice to copy entecavir, while not irrelevant to the obviousness analysis, does not amount to compelling evidence of nonobviousness here." Next, the court found "that Baraclude has been a commercial success, though a less dynamic one than BMS asserts in its briefs." The court then analyzed the testimony of a BMS expert, Dr. Gish, relating to skepticism of those in the art, but found that "in the absence of additional corroborating evidence . . . [Dr. Gish's] verbal claim of skepticism is simply not enough to weigh in BMS's favor as to this factor regarding nonobviousness." The court similarly found evidence of failure of others to be weak.
Teva has made out a strong prima facie case of obviousness. The evidence that it put forward at trial in that regard was multi-faceted and compelling. In addition, as to almost every significant portion of the prima facie case, Teva's position was not only bolstered by the opinion of its expert, Dr. Heathcock, but also by the testimony of BMS's expert, Dr. Schneller. On cross-examination, Dr. Schneller was forced to concede the accuracy of many significant points that Teva sought to assert as to that prima facie case. The force of this evidence was clear, and it was convincing.
As noted above, the evidence as to objective considerations was mixed. Some of those considerations redounded to the benefit of BMS's position as to nonobviousness to a degree, but as to a number of other considerations, the impact of that evidence was not particularly compelling. The totality of that evidence did not strongly persuade the Court as to entecavir's nonobviousness.
In addition to obviousness, Teva argued that the '244 patent is unenforceable due to inequitable conduct. Teva based its inequitable conduct allegation on the fact that prior art disclosing 2'-CDG was not cited to the PTO during prosecution (which, incidentally, strengthened Teva's obviousness position). Here, the court sided with BMS, finding that Teva did not demonstrate "that the single most reasonable inference in this case is that [BMS] had the specific intent to deceive the PTO, nor that the evidence requires a finding of deceitful intent in light of all of the circumstances."
Though successful in the district court, it is unclear when Teva will begin marketing its generic entecavir tablets, as Teva's ANDA has apparently not yet received tentative approval. In addition, according to the Orange Book, BMS holds a three-year exclusivity on Baraclude that expires in October 2013 and another three-year exclusivity that expires in October 2015. Meanwhile, BMS will very likely appeal today's decision to the Federal Circuit.
Novo Nordisk recently became the fourth company to ask FDA for guidance concerning whether patents on pre-filled drug delivery devices should be listed in the Orange Book. Novo markets several drug products as pre-filled pen-injector systems, including insulin and growth hormone products.
Whether information on patents relating to approved pre-filled drug delivery systems should be submitted to FDA for Orange Book listing if such patents neither disclose nor claim the active ingredient or formulation of the approved drug product.
Novo Nordisk's request follows similar requests submitted by GlaxoSmith Kline in 2005; AstraZeneca in 2006 and 2007; and Forest Laboratories in 2011. According to Novo, "To date, FDA has not substantively answered the advisory opinion requests or otherwise publicly addressed the patent listing issues they raise."
The Federal Food, Drug, and Cosmetic Act requires the sponsor of a New Drug Application to submit for listing in the Orange Book "any patent which claims the drug for which the applicant submitted the application or which claims a method of using such drug and with respect to which a claim of patent infringement could reasonably be asserted if a person not licensed by the owner engaged in the manufacture, use, or sale of the drug."
FDA stated that a key factor in determining whether to list a patent, therefore, is whether the patent claims the finished dosage form of the approved drug product. FDA noted that these finished dosage forms include "metered aerosols, capsules, metered sprays, gels, and pre-filled drug delivery systems" but do not include "bottles or containers and other packaging."
FDA's distinction between pre-filled drug delivery systems and product packaging remains unclear, however, because the term "pre-filled drug delivery system" is not defined. The Orange Book does not list "pre-filled drug delivery systems" as a dosage form in Appendix C (Uniform Terms); nor does FDA's Data Standards Manual Dosage Form Monograph (C-DRG-00201) provide any useful guidance.
Novo's request notes that in at least one instance a defendant in a Hatch-Waxman case filed a "delisting counterclaim" seeking the removal of a device-related patent. That case, King Pharms. v. Intelliject (D. Del.), was dismissed before the court ruled on the counterclaim. Novo argues that an advisory opinion from FDA addressing Novo's questions "could reduce the likelihood of patent delisting litigation and is in the interest of judicial economy." Novo also argues that the "patent notice" and "early patent challenge" functions of the Hatch-Waxman Act would be advanced if FDA were to issue such an advisory opinion.
Novo concludes its request by informing FDA--just as GSK, AstraZeneca, and Forest previously informed FDA--that in the absence of guidance from FDA that the listing of patents on pre-filled drug delivery devices is improper, Novo will submit such patents for listing in the Orange Book.
I recently spoke at the Global IP Convention in Bangalore, India. My presentation concerned lifecycle management strategies used by brand-name companies and some recent legal developments that may be helpful for generic companies responding to those strategies.
3. The following are not inventions within the meaning of this Act . . .
(d) the mere discovery of a new form of a known substance which does not result in the enhancement of the known efficacy of that substance or the mere discovery of any new property or new use for a known substance or of the mere use of a known process, machine or apparatus unless such process results in a new product or employs at least one new reactant.
Explanation: For the purposes of this clause, salts, esters, ethers, polymorphs, metabolites, pure form, particle size, isomers, mixtures of isomers, complexes, combinations and other derivatives of known substance shall be considered to be the same substance, unless they differ significantly in properties with regard to efficacy.
The Indian Supreme Court is currently considering a Novartis challenge to the constitutionality of Section 3(d), but the consensus at the Global IP Convention was that the Supreme Court would uphold the provision. Section 3(d) would likely prevent much of the patenting activity employed by brand-name companies in their strategy to maintain market dominance.
I asked Mr. Caleb if he was aware of a similar provision being adopted in any other countries. He advised that a similar provision has already been adopted in the Philippines and a number of other countries are in the process of adopting such a provision. This is certainly something pharmaceutical companies should monitor in the months ahead.

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