Source: https://www.orangebookblog.com/2007/05/index.html
Timestamp: 2019-04-20 06:30:08+00:00

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American Conference Institute will hold the 2nd west coast edition of its popular "Maximizing Pharmaceutical Patent Life Cycles" conference next week in San Francisco (at the beautiful Mark Hopkins hotel). ACI calls this "the only Hatch-Waxman conference specifically designed for the biopharmaceutical industry."
According to ACI, the conference will "bring the biopharmaceutical industry the critical information that it needs regarding the legal aspects of pharmaceutical patent life cycles. An esteemed faculty of biopharmaceutical industry and Hatch-Waxman experts will provide targeted information and commentary especially for biopharmas."
Additionally, two pre- and post-conference workshops are available: "Regulatory Fundamentals and IP Basics for Small Molecules and Biologics" on June 4; and "New Strategies for Obtaining Pharmaceutical Patent Extensions" on June 7.
The co-chairs of the conference are Martin A. Voet (Sr. VP & Chief IP Counsel, Allergan, Inc. and author of The Generic Challenge) and Robert C. Funsten (Shareholder, Stradling Yocca Carlson & Rauth). Additional details and registration information are available at the conference website.
In my view, the Solicitor General was correct in recommending denial of certiorari in Joblove, but erred in its characterization of the majority opinion. For example, the Solicitor General's brief implies that at the time of the settlement the parties intended to park Barr's 180-day exclusivity, preventing market entry by other generics. In fact, at the time of the settlement, the FDA interpreted Hatch-Waxman as requiring the first ANDA filer to "successfully defend" against a suit for infringement as a prerequisite to earning 180-day generic exclusivity. See 21 C.F.R. § 314.107(c)(1) (1995). Thus, the parties settled with the understanding that Barr was forfeiting its chance for 180-day exclusivity. The Second Circuit explicitly noted this fact, and that the settlement "cleared the field" for other generic challengers, a factor weighing against a finding of antitrust violation.
The Solicitor General's brief also criticized the majority opinion for applying an insufficiently stringent standard for scrutinizing reverse payment settlements, implying that the majority test would find a settlement valid unless the underlying lawsuit was a sham or "objectively baseless in the sense that no reasonable litigant could realistically expect success on merits." The brief also implied that the majority's approach was at odds with the standard articulated by the Eleventh Circuit in Schering and Valley Drug. But in fact, the Second Circuit test would find an antitrust violation if the underlying lawsuit was objectively baseless, or, in the alternative, if the terms of the settlement created "an extension of the monopoly beyond the patent's scope." Note that these are alternative tests--an antitrust violation could be found if the agreement exceeds the scope of the patent, regardless of whether the underlying suit is objectively baseless or a sham. This test is not substantially different from the Eleventh Circuit's test, which looks to the extent that the agreement exceeds "the scope of the exclusionary potential of the patent."
Both tests leave the door open for at least some limited of assessment of the merits of the underlying patent suit, for how can a court make a determination of the exclusionary potential of a patent without at least implicitly considering validity/enforceability and construing and applying the claims? Under both the Eleventh and Second Circuit approaches, a court could find that a settlement exceeds the reasonable scope of the patent grant in a situation where at the time of settlement the patent appeared likely to be found invalid or unenforceable. Although the brief asserts that in Schering the Eleventh Circuit "did not foreclose the possibility that a party challenging a patent settlement could rely on an ex ante view of the strength of the infringement claim," it provides no citation to any text in the Schering decision that would support this view. I have looked, and I don’t think there is anything that would necessarily render the Second and Eleventh Circuit tests inconsistent.
Note also that while the brief suggests that the correct standard would assess the merits of the underlying patent case, the FTC has in the past characterized such an assessment as "not supported by law or logic." Schering, 402 F.3d 1056, 1068 n.18.
Readers interested in a further discussion explaining the basis for my assertion that there is in fact no substantial split between the Eleventh and Second Circuits (as well as Sixth Circuit) on this issue might want to take a look at my recent article on reverse payment settlements: Christopher M. Holman, Do Reverse Payment Settlements Violate The Antitrust Laws?, 23 Santa Clara Computer & High Tech. L.J. 489 (2007). The article will soon be available on SSRN, or I would be happy to send a copy to anyone that is interested. My email is holmancm@umkc.edu.
Via the Antitrust Review and Pharmalot, the Solicitor General has recommended that the Supreme Court deny certiorari in Joblove v. Barr Labs, the most recent "reverse payments" case to be appealed to the Court. Last year, the Solicitor General advised the Court not to take the FTC v. Schering case. At the time, many observers thought this case might better present the reverse payments issue.
Whether the federal antitrust laws prohibit a brand name drug patent holder and a prospective generic competitor from settling patent infringement litigation by agreeing that the generic manufacturer will not challenge the validity of the patent or market its own version of the drug until the expiration of the patent, in exchange for a substantial payment from the patent holder.
The Solicitor General's brief advised the Court that the Second Circuit adopted an insufficiently stringent standard for scrutinizing reverse payment settlements when it held that a settlement is valid unless the underlying lawsuit was "objectively baseless in the sense that no reasonable litigant could realistically expect success on merits." In the Solicitor General's view, a court evaluating a reverse payment settlement should engage in a "broader inquiry concerning the patent holder's likelihood of success on that claim."
Ultimately, however, the Solicitor General concluded that this is not an appropriate case for review, since the "federal antitrust claims in this case appear to be moot, the factual setting is atypical and unlikely to recur, and subsequent regulatory changes may undercut one of the theories of competitive harm advanced by petitioners."
The Federal Trade Commission, which has campaigned vigorously against reverse payment settlements, is probably very disappointed with the Solicitor General's recommendation to deny cert. My understanding is that the FTC will not have an opportunity to submit its own brief in this case, since the government may only submit a single amicus brief to the Supreme Court (the FTC was a party in FTC v. Schering, so of course it submitted its own brief in that case). Officials at the FTC have revealed that their current strategy is to try to create a circuit split that the Supreme Court will have no choice but to resolve.
Last month (as we reported then), the U.S. District Court for the District of Delaware granted Merck's motion to dismiss the patent suit Merck filed against Apotex concerning generic Fosamax. The court indicated at the time that an opinion would "follow at the court's earliest convenience." On Monday, the court issued the promised opinion.
Merck moved to dismiss the case after granting Apotex a covenant not to sue on any of the nine patents-in-suit. Apotex opposed the motion on grounds that it was entitled to a "court decision" of invalidity or non-infringement, which would have triggered the first ANDA filer's 180-day exclusivity period. That would have allowed Apotex to launch its own generic Fosamax sooner--either by forcing the first filer to launch its generic Fosamax earlier or by causing the first filer to forfeit its exclusivity.
Having received a covenant not to sue, Apotex does not and cannot allege "unlawful conduct" attributable to Merck. Further, Apotex's articulated injury--delayed entry to the market--is not fairly traceable to Merck. There is no evidence to conclude that Apotex's delayed entry into the market is any different than what it would have been had Merck never sued it. Thus, Apotex's advancement of this case against Merck becomes merely a means to an end, where the desired "end" is a triggering event but the means to that end, the litigation itself, is not sanctioned under the current legal framework. To proceed to a substantive "court decision" on the merits of Apotex's claims of noninfringement or invalidity would amount to an impermissible advisory opinion.
The court also addressed Apotex's motion to amend its pleadings to add an antitrust counterclaim. Apparently, in its motion to amend Apotex argued that Merck's 30-month stay on FDA approval of Apotex's ANDA would not be terminated upon dismissal of the lawsuit, causing additional antitrust injury to Apotex. My understanding has always been that dismissal of a case terminates the 30-month stay. According to the district court, however, that is not so clear.
The court acknowledged the potential for abuse "if the mere filing of a patent infringement suit can result in an irrevocable 30-month stay," but in the end, concluded that Merck's actions were perfectly legal under the Hatch-Waxman regime. Therefore, according to the court, Apotex does not have a cognizable antitrust injury.
This afternoon, the Federal Circuit denied Pfizer's petition for rehearing and rehearing en banc of Pfizer v. Apotex, in which the court invalidated claims 1-3 of Pfizer's U.S. Patent No. 4,879,303. The '303 patent covers amlodipine besylate, the active ingredient in Norvasc.
Three of the twelve judges ruling on Pfizer's petition dissented from the decision not to rehear the case en banc: Newman, Lourie, and Rader. Each of the three filed dissenting opinions.
Judge Newman voiced strong disagreement with the three-judge panel opinion, writing that "the panel's application of the obvious-to-try standard is in direct conflict with precedent" and "the panel decision changes the criteria as well as the analysis of patentability." Judge Lourie expressed his view that "the panel erred in its legal determinations, and those errors will confuse the law relating to the rebuttal of a prima facie case of obviousness of a chemical compound." Both Newman and Lourie are chemists by training. Judge Rader stated that the panel gave insufficient deference to numerous factual findings of the district court, and substituted its own judgment on those issues. He concluded: "this decision calls into question countless pharmaceutical patents, which in turn could have a profoundly negative effect on investments into the design and development of new life-saving pharmaceuticals."
The most immediate beneficiary of today's decision may be Apotex. The FDA announced last month that it would grant final approval to Apotex's ANDA for generic Norvasc when the Federal Circuit issues a mandate in Pfizer v. Apotex. In addition to denying Pfizer's petition to rehear the case today, the Federal Circuit also granted Apotex's motion for expedited issuance of the mandate and issued the mandate. Thus, Apotex's final approval appears imminent.
As we previously reported, Mylan, who currently has the only approved ANDA for generic Norvasc, filed suit to enjoin FDA from approving any other generics. Mylan lost that case and appealed to the D.C. Circuit. Mylan might now file an emergency motion with the D.C. Circuit, aiming to prevent FDA from approving Apotex's ANDA until the appeal is decided.
More drama involving amlodipine--this time with Lotrel (made by Novartis), rather than Norvasc (made by Pfizer). Lotrel contains a combination of two active ingredients--amlodipine besylate and benazepril--whereas Norvasc contains only one. Both drugs are indicated for the treatment of high blood pressure and both are blockbusters.
Teva announced in a press release today that the FDA granted final approval to Teva's ANDA for generic Lotrel on Friday, Teva began shipping the product immediately, and the U.S. District Court for the District of New Jersey granted Novartis's motion for a temporary restraining order on Saturday, halting Teva's shipments.
Novartis and Teva have been locked in litigation over Teva's ANDA for generic Lotrel since 2004. The 30-month stay expired earlier this year and, probably sensing that Teva was close to obtaining final approval (and fearing an at-risk launch), Novartis moved for a preliminary injunction in March. The district court was set to hear arguments on that motion in July.
Novartis's TRO motion recounts the events leading up to the filing of the motion on Saturday, and reveals that Teva's only invalidity defense is obviousness. Although Novartis's TRO motion does not detail the parties' arguments (instead, it incorporates by reference Novartis's motion for preliminary injunction, which was filed under seal), I suspect that if obviousness is the primary issue in the litigation, Teva was emboldened to launch at-risk by the Supreme Court's recent decision in KSR v. Teleflex. Still, Teva seems to be laying it all on the line--especially considering that it is the 180-day exclusivity holder and its commercial launch triggered that exclusivity period. The clock is ticking.
Besides temporarily enjoining Teva from selling its generic Lotrel, the Order entered by the district court on Saturday requires Teva to immediately recall any generic Lotrel already shipped to customers. The court has scheduled a hearing on the matter for tomorrow at 11 am (eastern).
The patent-in-suit is U.S. Patent No. 6,162,802.
UPDATE: Teva announced Monday that the district vacated the temporary restraining order during the hearing Monday morning. The court ordered Teva and Novartis not to sell any generic Lotrel until at least next Tuesday, May 29, when the court holds a status conference. Read the AP story.
In a May 14 Order, the district court in D.C. denied all motions for reconsideration of its April 30 decision on Norvasc pediatric and 180-day exclusivity. FDA Law Blog has all the reconsideration briefs. Apotex and Mylan have now appealed to the D.C. Circuit.
The In Vivo Blog reports that "Democratic and Republican staffers involved in the follow-on biologics debate have reported good progress on the approval pathway and safety issues for follow-on biologics."
According to Red Herring, generic drug companies in India are very excited about the Supreme Court's recent KSR decision.
Pharmalot has this recent post on a White House trade deal favoring generic drug makers.
AP reports that the Phillippines government has petitioned to void Pfizer's Norvasc patent there.
Eisai owns U.S. Patent No. 5,045,552, which claims the chemical compound rabeprazole sodium, the active ingredient in Eisai's blockbuster proton-pump inhibitor Aciphex. Dr. Reddy's, Teva and Mylan filed ANDAs for generic Aciphex with paragraph IV certifications to the '552 patent. Aciphex has annual U.S. sales of over $1 billion and accounts for a large percentage of Eisai's U.S. revenue, so naturally Eisai filed suit against the generic applicants.
Last October (as we previously reported), Judge Gerard E. Lynch of the Southern District of New York granted Eisai's motion for summary judgment of patent validity and partially granted Eisai's motion for summary judgment of no inequitable conduct. Dr. Reddy's and Teva had already stipulated to infringement. Judge Lynch held a two-week bench trial on the remaining inequitable conduct issues in March, and last Friday he issued a 62-page opinion in favor of Eisai.
Eisai omitted certain data from a Rule 132 declaration filed in the prosecution of the '552 patent, and therefore the declaration was misleading.
Judge Lynch found that Dr. Reddy's and Teva failed to prove that the co-pending application and certain rejections made during its prosecution were of such a highly material nature as to support an inference of an intent to deceive. Moreover, he concluded that the defendants utterly failed to prove any degree of an intent to deceive--finding the Eisai witnesses to be highly credible. Judge Lynch further found that Dr. Reddy's and Teva failed to prove either materiality of the international patent publication or an intent to deceive the patent office by failing to disclose it. Finally, Judge Lynch found that the Rule 132 declaration was not in fact misleading, and that Eisai had no intent to deceive the PTO by omitting certain data from it.
Though Friday's ruling came in the litigations involving Dr. Reddy's and Teva, Mylan had previously agreed to be bound by the outcome in the two cases. The ruling is an especially bitter defeat for Dr. Reddy's--since it was the first ANDA filer and the 180-day exclusivity holder. Dr. Reddy's (and perhaps Teva too) is expected to appeal the decision to the Federal Circuit.
Last Thursday, the Federal Circuit heard oral arguments in Mylan's appeal of a district court decision upholding the validity of Janssen Pharmaceutica's patent on Risperdal (risperidone), an antipsychotic medication with over $2 billion in annual U.S. sales. On Friday, the Federal Circuit affirmed the decision under Rule 36 without issuing an opinion. The case is noteworthy because the central issue on appeal was obviousness and the judges asked numerous questions about the effect KSR on the case.
Much of the oral argument focused on whether the district court erred by rigidly applying a "lead compound standard," requiring Mylan to prove at trial that one of skill in the art would have chosen a single particular starting compound from which to develop the claimed compound. The district court had called this standard, set forth in the Federal Circuit's Yamanouchi v. Merck decision, a "factually-specific application of the 'motivation-suggestion-teaching' test."
The Federal Circuit judges specifically asked whether KSR called the lead compound standard into question. Counsel for Janssen replied, "no," arguing that whether you call it "lead compound analysis," "motivation," "reason," or "common sense," the district court's analysis was correct. Janssen's attorney further expressed his belief that the Supreme Court in KSR essentially endorsed the TSM test, so long as it is not rigidly applied.
Judges Gajarsa, Prost, and Otero (by designation from the Central District of California) presided over the oral argument. If you would like to listen to the argument, search for case no. 07-1021 on the oral arguments web-page of the Federal Circuit website.
Does FDA Need a Statutory Path to Approve Follow-on Biologics?
Much of the current discussion surrounding the proposed follow-on biologics bills assumes that a "statutory path" is necessary before FDA can implement an abbreviated biologics license application (BLA) process for biotechnology-derived therapeutic proteins. In fact, FDA probably already has the authority to create such a process by regulation, but so far has declined to do so.
The argument that FDA requires a statutory path is based largely on the fact that the PHSA (the statute governing the regulation of most biotechnology-derived therapeutic proteins) does not explicitly provide an abbreviated BLA approval processes analogous to the FDCA's 505(b)(2) "paper NDA" and 505(j) abbreviated NDA (ANDA). But the FDCA explicitly requires clinical trials for the approval of an NDA, so FDA arguably needs explicit statutory authorization to implement an abbreviated process that dispenses with the requirement of clinical trials. As noted in the House Report published in connection with the passage of Hatch-Waxman, the only statutory difference between a NDA and an ANDA is the requirement of human clinical trials.
The PHSA, on the other hand, does not require clinical trials for approval of a BLA, and hence no explicit statutory path should be required for biologics. FDA's regulations require clinical trials to show safety and efficacy of biologics approved under the BLA process, but these are regulations dating back to the mid-1970s (well before the approval of any biotechnology-derived proteins), and could be updated by FDA to dispense with such a requirement in some instances, assuming the science would support such a revision, without requiring Congress to amend the PHSA.
In 1996, a district court specifically found that FDA has the statutory authority under the PHSA to approve a comparable biologic without requiring new clinical trials. Berlex Labs v. FDA, 942 F.Supp. 19 (D.D.C. 1996). Although that case dealt with a change in manufacturing process implemented by the original manufacturer, with respect to the question of statutory authority the court's rationale should apply equally to a comparable protein produced by a different manufacturer.
During recent Congressional testimony, FDA's representative Dr. Woodcock was questioned on the supposed need for a statutory path. She walked a close line, at one point indicating that a statutory path was required, but on closer questioning conceding that the PHSA does not require clinical trials, and that the only statutory requirement is that the FDA ensure the "purity, potency and safety" of biologics approved under the Act. Members of Congress also queried whether the rationale of Berlex Labs v. FDA should not also apply to biologics, but did not receive a direct answer. Earlier, in January 2007, Reps. Dingell and Stupak sent a letter to FDA questioning whether a statutory path was really necessary, and asking for a response from FDA no later than February. To my knowledge, FDA has not responded.

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