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At the intersection of Patent and FDA Law

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  • Split Federal Circuit Panel Reinstates Jury Verdict of Induced Infringement in Coreg (carvedilol) Case

    GlaxoSmithKline v. Teva, No. 18-1976 (Fed. Cir. 2020)

         by Alex Menchaca

    In our last post, we reported that Chief Judge Stark of the District of Delaware granted Judgment as a Matter of Law of no induced infringement in a case concerning Coreg® (carvedilol) tablets, wiping away a $200 million jury verdict in favor of GSK and against Teva.

    In a precedential decision on October 2nd, a split Federal Circuit panel reversed that judgment, finding that the jury verdict was supported by substantial evidence. Judge Newman, joined by Judge Moore, wrote the majority opinion. Chief Judge Prost dissented.

    This note addresses primarily the Federal Circuit's treatment of Teva's "skinny label" as evidence of inducement. Teva sold with a skinny label from September 2007 until April 2011 and with a full label after April 2011. At the end of this note (in case you want to skip the juicy details), we state our hopes for the next steps in this case.

    A skinny label alone cannot support a determination of induced infringement. Warner-Lambert Co. v. Apotex Corp., 316 F.3d 1348, 1364-65 (Fed. Cir. 2003) ("the request to make and sell a drug labeled with a permissible (non-infringing) use cannot reasonably be interpreted as an act of infringement (induced or otherwise) with respect to a patent on an unapproved use, as the ANDA does not induce anyone to perform the unapproved acts required to infringe.").

    The question then is what was the additional evidence, as evaluated by the Federal Circuit, that justified a jury verdict of induced infringement. That additional evidence had to show "an affirmative act to encourage infringement with the knowledge that the induced acts constitute patent infringement." Power Integrations, Inc. v. Fairchild Semiconductor Int'l, Inc., 843 F.3d 1315, 1332 (Fed. Cir. 2016)).

    The claim at issue included detailed instructions for administering the drug:

    1. A method of decreasing mortality caused by congestive heart failure in a patient in need thereof which comprises administering a therapeutically acceptable amount of carvedilol in conjunction with one or more other therapeutic agents, said agents being selected from the group consisting of an angiotensin converting enzyme inhibitor (ACE), a diuretic, and digoxin,

    wherein the administering comprises administering to said patient daily maintenance dosages for a maintenance period to decrease a risk of mortality caused by congestive heart failure, and said maintenance period is greater than six months.

    According to the claim, there must be daily administering for a period greater than six months. If there is no daily administering, there is no infringement. If there is no six months of administering, there is no infringement. And, if Teva did not undertake an affirmative act to induce those administering claim limitations, there is no induced infringement. Global-Tech Appliances, Inc. v. SEB S.A., 563 U.S. 754, 766 (2011) ("we now hold that induced infringement under § 271(b) requires knowledge that the induced acts constitute patent infringement."); Ericsson, Inc. v. D-Link Sys., Inc., 773 F.3d 1201, 1219 (Fed. Cir. 2014) ("In order to prove induced infringement, the patentee must show that the alleged infringer performs, or induces another party to perform, every single step in the method.")

    So what evidence did the Federal Circuit identify that the jury relied on as an affirmative act by Teva to induce physicians to undertake daily administering for greater than six months? Spoiler – it's really hard to find.

    The evidence introduced at trial and referenced by the Federal Circuit is described below with discussion from both the majority and the dissent. There is a lot of discussion for some of the evidence, so we limited our recitation to the best quotes (unless indicated otherwise the below are direct quotes from the opinion):

    A general statement by the majority: "Teva’s promotional materials referred to Teva’s carvedilol tablets as AB rated equivalents of the Coreg® tablets."

    Majority

    • [GSK's expert], 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.

    Dissent

    • [I]n closing arguments to the jury, GSK's counsel acknowledged that "the fact that Teva said they were AB rated isn’t enough to prove inducement . . . . [W]e have to show you more than just the AB rating."
    • In marketing its generic carvedilol, Teva never stated that it was approved, or could be used, to treat CHF. In fact, the record suggests Teva hardly marketed its generic at all.
    • [E]ven if Teva's documents suggested using its carvedilol products to treat CHF, which they do not, such a suggestion would not be enough to induce infringement of the ’000 patent. ([GSK's doctor expert]agree[d] that not every CHF patient treated with carvedilol infringes the claimed method). 

    Teva June 9, 2004 press release describing Teva’s carvedilol as the "AB-rated generic equivalent of GSK's Coreg® tablets."

    Majority

    • [GSK's expert] testified that he saw the 2004 press release, in which "Teva is telling doctors that they had received tentative approval for generic carvedilol, and that its final approval is anticipated in 2007."
    • He testified that Teva was telling him, as a physician, that Teva was "expecting to have a generic version of GlaxoSmithKline Coreg that is AB rated, and that it is indicated for the treatment of heart failure."

    Dissent

    • [The 2004 press release was] published before the '000 patent issued in 2008 and therefore cannot alone be an act of infringement.
    • [T]he 2004 press release . . . reports only "tentative approval." . . . The suggestion that a practicing physician would (or should) rely on an announcement for "tentative approval" in making prescribing decisions over three years in the future seems unlikely.
    • GSK's counsel acknowledged that "the fact that Teva said they were AB rated isn't enough to prove inducement."

    Teva's 2007 press release remained on Teva's website; screenshot bearing the date "4/14/2015" with the caption . . . “Teva Announces Approval and Shipment of Generic Coreg® Tablets”

    Majority

    • [GSK's expert] told the jury that [the 2007 press] release "indicates that we should be able to prescribe generic carvedilol for heart failure."
    • [T]he 2007 press release remained on Teva's website throughout the life of the '000 patent [which the Federal Circuit characterized as] continued affirmative promotion of its carvedilol tablet as the AB generic equivalent of Coreg®.

    Dissent

    • Teva's short [2007] press release stated that it had been granted "final approval . . . to market . . . Generic . . . Coreg® (Carvedilol) Tablets."
    • [The 2007 press release was] published before the '000 patent issued in 2008 and therefore cannot alone be an act of infringement.
    • [P]assive maintenance of the pre-issuance press releases [on the Teva website] is not an affirmative act of inducement.
    • Teva's press releases . . . do not promote treating CHF at all.

    Teva Spring 2008 Product Catalog [listing the AB rating of Teva's carvedilol]

    Majority

    • [GSK's expert] 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."
    • GSK [regulatory expert] . . . explained the drug approval process, and explained that the AB-rating means that "if the generic drug is used in accordance with its label, you would expect it to have the same clinical effect" as the brand drug. She introduced Teva's product catalogs that "list the AB ratings and they compare Teva's carvedilol with Coreg on that table with carvedilol on the left and Coreg on the right,"

    Dissent

    • The product catalogs likewise said nothing about the product’s indications.
    • GSK's counsel acknowledged that "the fact that Teva said they were AB rated isn’t enough to prove inducement."
    • GSK's [regulatory expert] testified that AB rating "is an indication that the product is therapeutically equivalent when used as labeled" and [not] with respect to the off-label uses."

    None of the cited evidence supports a finding of an affirmative act by Teva to induce physicians to undertake the administering steps. As the dissent notes, "the Majority seems to rely on references to Teva's 'AB rating' or therapeutic equivalence as evidence of inducement." But that also cannot support induced infringement by Teva, GSK's counsel acknowledged that.

    With respect to the full label period, the only additional evidence was the full label and product reference guides. The reference guides stated nothing more than that Teva's generic was "AB Rated and bioequivalent to Coreg® Tablets." The full label included reference to treatment of CHF, but there was no evidence that any doctor even read the full label. Still, it seems to us, not enough.

    We think the dissent has the better position. But the dissent overstates the majority's view when it states that the "Majority [holds] that the content of Teva's skinny label can itself establish inducement." The majority did not really say that, generally stating: "[p]recedent has recognized that the content of the product label is evidence of inducement to infringe" (citing cases).

    The real problem in the majority opinion is that it conflates its treatment of the skinny label period with that of the full label period. The majority lumps the documentary evidence for both periods into one paragraph (Slip Op. pp. 12-13) and glosses over the language distinctions of the labels (Slip Op. pp. 16-17). Perhaps that is why the dissent understood the majority opinion to "nullif[y] Congress's statutory provision for skinny labels—creating liability for inducement where there should be none."

    What would we like to see happen in this case? We would like to see the panel or the en banc Federal Circuit revisit this opinion and clearly break out the skinny label period from the full label period. Everybody involved in the case understood that each period deserved its own treatment; the dissent emphasized that GSK's counsel argued "[n]o label, no inducement." There simply is no evidence to support a finding of induced infringement during the skinny label period. A clear statement to that effect following Supreme Court and Federal Circuit precedent would undo the damage this opinion could do to the rights of ANDA applicants to pursue approval of skinny labels and file Section viii statements rather than paragraph IV certifications.

    Regarding the full label period? Based on the evidence detailed in the opinions, we don’t see inducement. But that is what the jury considered and perhaps the Federal Circuit may simply rely on that jury finding.

  • Judge Stark (D. Del.) Holds Generic Label Including Patented Indication is Insufficient to Prove Inducement

    GlaxoSmithKline v. Teva, No. 14-878-LPS-CJB (D. Del.)

        by Aaron F. Barkoff

    In an opinion last week, Judge Stark of the District of Delaware granted Teva's motion for judgment as a matter of law that GSK failed to present sufficient evidence to support a jury verdict that Teva induced infringement of U.S. Patent No. RE40,000.  Judge Stark's decision effectively vacates a jury award of more than $200 million to GSK.

    Here is an abbreviated chronology of the relevant facts:

    • May 1997: GSK obtains FDA approval of Coreg® (carvedilol) tablets for the treatment of congestive heart failure (CHF)
    • June 1998: U.S. Patent No. 5,760,069 issues to GSK, claiming a method of treating CHF by administering carvedilol
    • March 2002: Teva files an ANDA for carvedilol tablets with a para. III certification to U.S. Patent No. 4,503,067, which claims the carvedilol compound, and a para. IV certification to the '069 patent
    • March 2007: the '067 patent expires
    • August 2007: Teva amends its para. IV certification against the '069 patent to a section viii statement, carving out the CHF indication from its label and leaving indications for hypertension and left ventricular dysfunction
    • September 2007: FDA approves Teva's ANDA; Teva launches generic carvedilol
    • January 2008: the '069 patent reissues as the '000 patent
    • April 2011: Teva amends its label, adding back the CHF indication, making Teva's label essentially a copy of GSK's full label
    • June 2015:  the '000 patent expires

    Judge Stark held a seven-day jury trial last year.  The jury found that Teva willfully induced infringement of certain claims of the '000 patent during two time periods: (1) January 2008 to April 2011 (the "skinny label" period); and (2) May 2011 to June 2015 (the "full label" period).  The jury awarded $234 million in lost profits and $1.4 million in reasonable royalty damages to GSK.  The parties then filed post-trial motions.

    In granting Teva's motion for JMOL, the court summarized its conclusion as follows:

    The Court agrees with Teva that neither sufficient nor substantial evidence supports the jury's finding of inducement.  GSK failed to prove by a preponderance of the evidence that "Teva's alleged inducement, as opposed to other factors, actually caused the physicians [i.e., as a class or even at least one of them] to directly infringe," by prescribing generic carvedilol and to do so for the treatment of mild to severe CHF.  Without proof of causation, which is an essential element of GSK's action, a finding of inducement cannot stand.

    The court's decision that no reasonable jury could have found that Teva induced infringement of the '000 patent during the skinny label period is not surprising.  But the court's decision of no inducement during the "full label" period is unexpected.

    The court found that many factors–but not Teva's label or marketing materials–caused doctors to prescribe generic carvedilol.  For instance, the court found:

    In addition to the knowledge and experience that ordinarily skilled cardiologists had acquired by July 2007 about the benefits of treatment with carvedilol, such doctors had access to American Heart Association and American College of Cardiology guidelines, carvedilol research studies published in the New England Journal of Medicine, The Lancet, and the British Heart Journal, GSK's own Coreg® label and product insert, and GSK's extensive promotional activity–totaling nearly $1 billion–which included sending doctors to hospitals, giving seminars, and detailing, marketing, and advertising Coreg®.

    Further, Teva showed that once generic carvedilol entered the market in September 2007, and continuing beyond 2007, doctors continued prescribing carvedilol (be it Coreg® or a generic) in the same manner as they had prior to the generics' entrance, as they based their prescription decisions on the various factors addressed above without relying on Teva's–or any other generic manufacturers'–label.  GSK's expert, Dr. McCullough, testified that he had not read Teva's generic label before he started writing prescriptions for carvedilol.  As GSK concedes, prior to the generics' entrance into the market in 2007, physicians already knew how to use carvedilol for treating CHF.  Three cardiologists testified at trial . . . and all three agreed that even in September 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.  None viewed generic labeling, including Teva's label, as impacting prescribing behavior.

    As Teva correctly notes, no direct evidence was presented at trial that any doctor was ever induced to infringe the '000 patent by Teva's label (either skinny or full).  There was no direct evidence that Teva's label caused even a single doctor to prescribe generic carvedilol to a patient to treat mild to severe CHF.  Hence, in order to uphold the verdict, the Court must find in the record substantial evidence to render it reasonable for the jury to have inferred that at least one doctor was so induced.  GSK, as the verdict winner, is entitled to the benefit of all reasonable inferences that may be drawn from the evidence presented to the jury.  The Court's determination, however, is that–given the dearth of evidence that doctors read and understand and are affected by labels, and given the vast amount of evidence that doctors' decisions to prescribe carvedilol during the relevant periods were influenced by multiple non-Teva factors–such an inference was an unreasonable one for the jury to have drawn.

    The court distinguished more typical ANDA cases that involve a method-of-use patent, in which the patent owner alleges inducement of infringement before a generic launch and the court heavily relies on the proposed ANDA label when evaluating the inducement claim:

    For instance, GSK directs the Court to Sanofi v. Watson Laboratories Inc., 875 F.3d 636, for the proposition that the marketing of a generic drug with labeling that encourages infringement can be viewed as causing infringement despite the fact that the innovator company published the results of clinical studies and promoted the patented use.  That case does not persuade the Court to reach a different conclusion than described above.  Sanofi involved the ordinary Hatch-Waxman framework, where a claim of induced infringement is filed before the generic has launched its product, and necessarily, before the generic has even attempted to communicate with any direct infringer.  In those cases, as this Court held during earlier portions of this case, the focus must be on intent, rather than actual inducement.  Here, by contrast, GSK filed its case almost seven years after Defendants launched their generic carvedilol products into the market.  Hence, GSK's inducement claims are not premised on a hypothetical, but instead must be supported by sufficient evidence as to what actually happened during the relevant time period.  This Court has decided that reliance on a label and speculation about what may occur in the future cannot substitute for actual evidence about what has actually occurred in the past when, as in this case, there has been a period of actual, past conduct that is pertinent to infringement.

    This case is relatively unique–particularly because it involved an at-risk launch.  It will be interesting to see how the case affects litigation strategies used in other ANDA cases involving method-of-use patents.  And we will certainly be paying attention to the inevitable appeal.

  • PTAB Grants Hospira’s Request for Rehearing, Institutes IPR of Herceptin Patent

    Hospira, Inc. v. Genentech, Inc., IPR2017-00731 (PTAB)

        by Aaron F. Barkoff

    Apparently it is not impossible to change the PTAB's mind.  In a rare decision last week, the Board granted Hospira's request for rehearing of its earlier decision denying institution, and instituted review of U.S. Patent No. 7,846,441.  Genentech is expected to assert the '441 patent in BPCIA litigation over biosimilar versions of Herceptin (trastuzumab).

    The '441 patent, entitled "Treatment with Anti-ErbB2 Antibodies," claims a method of treating a cancer "characterized by overexpression of ErbB2 receptor, comprising administering a combination of an intact antibody which binds to epitope 4D5 within the ErbB2 extracellular domain sequence and a taxoid, in the absence of an antracycline derivative."

    In its Petition for IPR, Hospira argued that the prior art disclosed the claim limitation "in the absence of an antracycline derivative" because:

    (1) the cardiotoxicity of anthracycline derivatives was well known in the prior art; (2) both preclinical and clinical
    studies employed the combination of an anti-ErbB2 antibody "with paclitaxel or anthracycline, not together;" and (3) Baselga ʼ94 shows that the combination with paclitaxel was superior to the combination with doxorubicin, an anthracycline derivative.

    Genentech countered that Hospira did not show that an ordinary artisan would have avoided anthracyclines when pursuing the combination therapy of antiErbB2 antibody with a taxoid."  The Board agreed, and therefore denied institution.

    In its decision on Hospira's petition for rehearing last week, the Board reversed its earlier decision, explaining:

    In its Request for Rehearing, Petitioner contends that we erred in interpreting the limitation "in the absence of an anthracycline derivative" as requiring "avoidance" of an anthracycline derivative.  According to Petitioner, this term "is a negative limitation that is satisfied by anti-ErbB2 antibody–paclitaxel combinations that do not include an [anthracycline] derivative."  After reconsidering the current record, we find Petitioner's argument persuasive.  In particular, because Baselga '94 suggests a therapeutic composition consisting of an anti-ErbB2 antibody and paclitaxel, and does not suggest that doxorubicin must necessarily be included as part of the same treatment regimen, we are persuaded that the reference satisfies the limitation "in the absence of an anthracycline derivative."

    In support of its decision, the Board cited Upsher-Smith Labs., Inc. v. Pamlab, L.L.C., 412 F.3d 1319, 1322 (Fed. Cir. 2005) for its conclusion that a claim to a composition that is "essentially free of antioxidants" is anticipated when the prior art teaches "optional inclusion" of antioxidants, "despite no express teaching to exclude the antioxidants."

    Although Hospira did not cite the Upsher-Smith case in its Petition (or propose a construction of the disputed claim limitation), it did so in its request for rehearing.

  • Functional Claiming of Antibodies: (Continue to) Proceed With Caution

    CAFC holds that later-developed antibody species may be evidence that a claimed antibody genus is invalid for lack of written description, and casts doubt on the “antibody exception”

    Amgen Inc. v. Sanofi, No. 2017-1480 (Fed. Cir. October 5, 2017)

        by Christopher P. Singer, Ph.D.

    In a precedential opinion yesterday, the Federal Circuit refined the manner in which it applies the written description requirement to antibody claims. Specifically, the court clarified that “post-priority-date evidence of a particular species can reasonably bear on whether a patent” having claims to a genus fails the written description requirement of 35 U.S.C. § 112. In addition, the court cast further doubt on the “newly characterized antigen” test–also known as the “antibody exception” to written description.

    As brief background, Amgen sued Sanofi alleging that the cholesterol-lowering drug Praluent® (alirocumab) infringed U.S. Patents 8,829,165 and 8,859,741. The patents are directed to antibodies that bind PCSK9 and their use in methods of treating hypercholesterolemia. The court identified claim 1 of the ‘165 Patent as representative:

    1. An isolated monoclonal antibody, wherein, when bound to PCSK9, the monoclonal antibody binds to at least one of the following residues: S153, I154, P155, R194, D238, A239, I369, S372, D374, C375, T377, C378, F379, V380, or S381 of SEQ ID NO:3, and wherein the monoclonal antibody blocks binding of PCSK9 to LDLR.

    Sanofi conceded infringement of the claims but alleged the patents were invalid for lack of written description and enablement, and for obviousness.

    Post-priority-date evidence

    During litigation, Sanofi offered evidence of later-developed antibodies, including alirocumab, in support of its argument that the patents were invalid for lack of enablement and written description. The district court excluded the post-priority-date evidence, reasoning that it failed to illuminate the state of the art at the time of filing and was irrelevant for any other purpose. The Federal Circuit ultimately reversed the district court on this issue and remanded for a new trial on both 112 issues.

    Citing to its 2010 en banc decision in Ariad v. Eli Lilly, the court reaffirmed that written description is determined based on the state of the art as of a patent’s priority date and that evidence which illuminates the state of the art only subsequent to the priority date is not relevant to written description. Nevertheless, it found that the circumstances of this case were distinguishable:

    Evidence showing that a claimed genus does not disclose a representative number of species may include evidence of species that fall within the claimed genus but are not disclosed by the patent, and evidence of such species is likely to postdate the priority date. If such evidence predated the priority date, it might well anticipate the claimed genus.

    Here, Appellants sought to introduce evidence not to illuminate the state of the art on the priority date but to show that the patent purportedly did not disclose a representative number of species. As a logical matter, such evidence is relevant to the representativeness question. Simply, post-priority-date evidence of a particular species can reasonably bear on whether a patent “fails to disclose a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus.” (slip opinion at 8-9, quoting Ariad).

    The court acknowledged that it had not ruled on this specific question to date, but justified its holding as following “the common-sense logic of admissibility” from recent cases including Abbott GmBH & Co., KG v. Centocor Ortho Biotech, Inc., 971 F.3d 171 (D. Mass. 2013) and Abbvie Deutschland GmbH v. Janssen Biotech Inc., 759 F.3d 1285 (Fed. Cir. 2014). It also reasoned that this case was distinguishable from In re Hogan (559 F.2d 595 (CCPA 1977), clarifying that the decision only prohibits introduction of post-priority-date evidence to illuminate the state of the art, and is silent with regard to the use of such evidence to show that a patent fails to disclose a representative number of species.

    Newly characterized antigen test

    Another issue on appeal related to whether the district court’s jury instruction concerning written description was improper for including the sentence:

    In the case of a claim to antibodies, the correlation between structure and function may also be satisfied by the disclosure of a newly characterized antigen by its structure, formula, chemical name, or physical properties if you find that the level of skill and knowledge in the art of antibodies at the time of filing was such that production of antibodies against such an antigen was conventional or routine. (slip opinion at 12).

    Finding for Sanofi, the court held the sentence to be improper, relying heavily on its decision in Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341 (Fed. Cir. 2011), and characterizing it as “the only case where we examined the ‘newly characterized antigen’ test in [ ] detail.” (slip opinion at 15). As one concern, the court indicated that the test may allow the enablement requirement (make and use) to subsume the written description requirement in clear violation of its holding in Ariad. In signaling what could be the death knell, the court stated that “the ‘newly characterized antigen’ test flouts basic legal principles of the written description requirement . . . [and] allows patentees to claim antibodies by describing something that is not the invention, i.e., the antigen” in contradiction of the quid pro quo regarding the disclosure of the invention. (slip opinion at 18).

    From a practitioner’s point of view, it will be interesting to follow this case on remand. Recent cases such as Abbvie Deutschland v. Janssen have highlighted the risk of relying on functional language, rather than sequence features, to claim antibodies. Conversely, older cases that deal with written description, such as Enzo Biochem, Inc. v. Gen-Probe Inc., 323 F.3d 956 (Fed. Cir. 2002) and Noelle v. Lederman, 355 F.3d 1343 (Fed. Cir. 2004), provide a basis to argue that functional language, coupled with some amount of structure that correlates to the recited function, can satisfy the written description requirement.

    While Amgen’s claims do not include any sequence features common to the claimed antibody genus, such as a CDR, they include some amount of structural description of the epitope to which the antibody genus binds, which distinguishes them from the purely functional/activity-based limitations in the claims at issue in the Centocor and Abbvie Deutschland cases. The court will no doubt have its hands full in determining whether the description of the epitope structure recited in Amgen’s claims will be adequate to fulfill the written description requirement (retaining some part of the “newly characterized antigen” test), and whether the strength of the post-priority-date evidence will demonstrate that the claims lack written description support.

  • Federal Circuit Holds That Specific Personal Jurisdiction Exists Anywhere an ANDA Applicant Intends to Market its ANDA Product

    Acorda Therapeutics v. Mylan Pharms., 2015-1456 (Fed. Cir. March 18, 2016)

    AstraZeneca v. Mylan Pharms, 2015-1460 (Fed. Cir. March 18, 2016)

        by Alex Menchaca

    Where is an ANDA applicant subject to personal jurisdiction when the only act of infringement is "artificial" infringement under 35 U.S.C. § 271(e)(2)(A)? This question has generated a great deal of interest recently–especially since the Supreme Court's Daimler decision two years ago. In a precedential opinion on Friday, the Federal Circuit answered the question and determined that personal jurisdiction exists in any state where the ANDA applicant intends to market its product–essentially everywhere in the United States.

    Mylan filed ANDAs in connection with Ampyra® (dalfampridine), Onglyza® (saxagliptin), and Kombiglyze® (saxagliptin/metformin). Acorda markets Ampyra® for the treatment of multiple sclerosis while AstraZeneca markets Onglyza® and Kombiglyze® for the treatment of type 2 diabetes. Both Acorda and AstraZeneca sued Mylan in Delaware, and Mylan filed motions to dismiss for lack of personal jurisdiction in both cases.

    Both motions were denied. In the dalfampridine case, Judge Stark held that Mylan was subject to both general and specific personal jurisdiction. In the saxagliptin case, Judge Sleet held that Mylan was subject to specific personal jurisdiction, but not general personal jurisdiction. Mylan sought and obtained interlocutory review by the Federal Circuit of both of those orders. The appeal attracted six amicus filings, including briefs from GPhA, Teva, BIO, and PhRMA.

    The Federal Circuit majority opinion limited its analysis to specific personal jurisdiction. The court began with the rule from International Shoe:  specific personal jurisdiction may be exercised over a defendant "when the defendant has certain minimum contacts with the forum such that the maintenance of the suit does not offend traditional notions of fair play and substantial justice." Further, "the minimum contacts requirement focuses on whether the defendant's suit-related conduct creates a substantial connection with the form State."

    In short, the Federal Circuit held that specific personal jurisdiction may be exercised over Mylan because "the minimum-contacts standard is satisfied by the particular actions Mylan has already taken–its ANDA filings–for the purpose of engaging in that injury-causing and allegedly wrongful marketing conduct in Delaware."

    The fact that the infringement at issue in the cases was "artificial" infringement under 35 U.S.C. § 271(e)(2)(A) was used by the Federal Circuit to support its holding. The court explained that this statute is directed to the real-world consequence of marketing a generic in competition with the brand name drug: "concrete, non-artificial acts of infringement." Having determined that infringement under section 271(e)(2)(A) carries real-world consequences (and is more than an "artificial" construct), the Federal Circuit analogized the lawsuits against Mylan for intended future actions to "suits for retrospective relief based on past acts" and noted that the Supreme Court has defined minimum contacts in those retrospective contexts:

    In a formulation worded to address suits for retrospective relief based on past acts, the Supreme Court has said that the minimum-contacts requirement is met when the defendant "purposefully directed" activities at the forum, and the litigation results from alleged injuries that "arise out of or relate to" those activities.

    The Federal Circuit explained that Mylan's ANDA filings constituted activities purposefully directed at Delaware and that the lawsuits resulted from injuries that the plaintiffs would sustain by Mylan's activity:

    Mylan's ANDA conduct is "suit-related" and has a "substantial connection" with Delaware because the ANDA filings are tightly tied, in purpose and planned effect, to the deliberate making of sales in Delaware (at least) and the suit is about whether that in-State activity will infringe valid patents. Thus, Mylan's ANDA filings constitute formal acts that reliably indicate plans to engage in marketing of the proposed generic drugs. Delaware is undisputedly a State where Mylan will engage in that marketing if the ANDAs are approved. And the marketing in Delaware that Mylan plans is suit-related: the suits over patent validity and coverage will directly affect when the ANDA can be approved to allow Mylan's Delaware marketing and when such marketing can lawfully take place.

    Although the majority opinion did not address the issue of general personal jurisdiction, Judge O'Malley's concurring opinion did. Judge O'Malley wrote that a straightforward application of Supreme Court precedent also establishes general personal jurisdiction in these cases. It may be, however, that the question of general personal jurisdiction is now moot given the court's analysis of specific personal jurisdiction.

  • Federal Circuit Hands Mixed Ruling to Momenta on 271(g) and 271(e)(1) Issues

    Momenta and Sandoz v. Teva, No. 2014-1274 (Fed. Cir.)

    Momenta and Sandoz v. Amphastar, No. 2014-1276 (Fed. Cir.)

        by Aaron F. Barkoff

    In a precedential opinion today, in companion cases concerning generic enoxaparin, the Federal Circuit reached two decisions that pharmaceutical companies should take note of:

    1.    Teva's enoxaparin is not "made by" a patented process within the meaning of § 271(g) because the process is used merely "to ensure that the intended product or substance has in fact been made."  In other words, the process simply "provides information regarding a substance that has already been made but does not transform it."

    2.    The safe harbor of § 271(e)(1) does not apply to Amphastar's "routine quality control testing of each batch of generic enoxaparin as part of the post-approval, commercial production process."

    Momenta and Sandoz, which were the first to market a generic version of Sanofi's anticoagulant Lovenox (enoxaparin), asserted U.S. Patent No. 7,575,886 against Teva and Amphastar.  The '886 patent claims methods for analyzing enoxaparin to determine whether it has the appropriate chemical structure.  Momenta alleged that Teva's and Amphastar's enoxaparin manufacturing processes infringe the '886 patent.

    The Federal Circuit's decision concerning § 271(g) was a split decision, with Judges Wallach and Moore in the majority and Judge Dyk dissenting.  According to the majority opinion, Momenta argued that its patented method "is used [by Teva] to select and separate batches of intermediate drug substance that conform to USP requirements for enoxaparin from batches that do not," and that selected batches are then used to make the finished drug product.  The majority concluded, "Although Momenta's arguments are not without merit, it is more consonant with the language of the statute, as well as with this court's precedent, to limit § 271(g) to the actual 'ma[king]' of a product, rather than extend its reach to methods of testing a final product or intermediate substance to ensure that the intended product or substance has in fact been made."

    Judge Dyk, in dissent, argued that "the quality control testing method of the '886 patent is a necessary intermediate step in the manufacture of enoxaparin."  He warned:

    Patents on purification methods or the quality control method at issue here, which may be integral to the regulatory or commercial viability of a product, but which do not create or transform a product, combine components, or confer new properties, could be freely infringed simply by outsourcing those processes abroad.  Congress could not have intended to create this loophole when it sought to protect process patent owners from foreign competitors using U.S. manufacturing processes abroad.

    The Federal Circuit's decision concerning the 271(e)(1) safe harbor is especially interesting because the court previously reached the opposite conclusion during the preliminary injunction phase of the case (Momenta I).  There, the court found that Amphastar's testing according to the patented method was protected by the safe harbor because it was "necessary both to the continued approval of the ANDA and to the ability to market the generic drug."  The majority in that case distinguished the facts from those in Classen, where the court held that § 271(e)(1) "does not apply to information that may be routinely reported to the FDA, long after marketing approval has been obtained."  In Momenta I, Judge Moore wrote the opinion for the majority, which included Judge Dyk, while Chief Judge Rader vigorously dissented.

    This time around, the panel (which again included Judges Dyk and Moore) unanimously held that § 271(e)(1) does not exempt Amphastar's testing.  The court states, "With the benefit of additional briefing in the current appeals, which reflects the full district court record developed by all parties after the preliminary injunction phase, we conclude Amphastar's submissions are appropriately characterized as 'routine.'"  According to the court, "The conclusion in Momenta I that Amphastar's commercial use of Momenta's patented method falls within the safe harbor of § 271(e)(1) would result in manifest injustice.  Amphastar points to no case, until Momenta I, extending immunity under § 271(e)(1) to encompass activities related to ongoing commercial manufacture and sale."  Thus, the court vacated the district court's grant of summary judgment to Amphastar and remanded the case.

  • Amgen Wins Temporary Injunction Against Sandoz in Landmark Biosimilars Case

    Amgen v. Sandoz, No. 15-1499 (Fed. Cir. May 5, 2015)

        by Aaron F. Barkoff

    In a per curium Order today, the Federal Circuit granted Amgen's Emergency Motion for an Injunction Pending Appeal, stalling, at least temporarily, Sandoz's commercial launch of Zarxio, a biosimilar version of Amgen's Neupogen (filgrastim). Zarxio is the first biosimilar product approved by FDA under the Biologics Price Competition and Innovation Act of 2009 (BPCIA). FDA approved Zarxio on March 6, and Sandoz agreed not to commercially launch the product until May 11 or a Federal Circuit ruling in its favor.

    The primary issue in the case is whether the pre-litigation information-exchange provisions of the BPCIA are mandatory, as Amgen argues, or optional, as Sandoz contends. The BPCIA states that a biosimilar applicant "shall provide" a copy of its FDA application and manufacturing information to the Reference Product Sponsor (RPS)–here, Amgen. The statute further states that in the event that a biosimilar applicant fails to provide its application and manufacturing information, the RPS may file a declaratory judgment action against the applicant. Sandoz argues that a biosimilar applicant therefore has a choice: either provide a copy of its application and manufacturing information to the RPS and proceed to the subsequent information-exchange provisions of the BPCIA (including the exchange of patent lists, invalidity and non-infringement contentions, etc.), or accept the consequence of a declaratory judgment action filed against it.

    Amgen filed suit against Sandoz last October, alleging state-law claims of unfair competition and conversion based on Sandoz's alleged failure to comply with the BPCIA, as well as patent infringement. With Sandoz's biosimilar application proceeding quickly toward FDA approval, Amgen filed a motion for preliminary injunction against Sandoz in February. On March 19, the district court denied Amgen's motion, ruling that the information-exchange provisions of the BPCIA are optional and that Sandoz fully complied with the law.

    Amgen immediately appealed to the Federal Circuit, and, two days after the district court denied Amgen's motion for injunction pending appeal, filed the emergency motion that the court granted today. Amgen's appeal attracted the support of three amicus filings, by BIO, AbbVie, and Janssen, while GPhA, Celltrion, and Hospira filed amicus briefs in support of Sandoz.

    Amgen and Sandoz requested an expedited appeal schedule, which the Federal Circuit granted.  Briefing is complete, and the court scheduled oral argument for June 3rd. The standard for granting a motion for injunction pending appeal is high–"whether the movant has made a strong showing of likelihood of success on the merits." It therefore appears likely that that Federal Circuit will ultimately reverse the district court and rule that the pre-litigation information-exchange provisions of the BPCIA are mandatory.

  • ACI “Summit on U.S. Biosimilars,” Munich, Germany, April 20-21

    McAndrews Shareholder Sandra Frantzen will be one of the featured speakers at American Conference Institute's "Summit on U.S. Biosimilars" conference in Munich, Germany, April 20-21.  Ms. Frantzen will be speaking on "Incorporating Inter-Partes Review and New USPTO Procedures into Branded and Biosimilar Litigation Strategies."

    Other speakers include in-house counsel and executives from AbbVie, Boehringer Ingelheim, IPM Biotech, PAREXEL, Sandoz, and Sanofi, as well as outside counsel from U.S. and European firms.

    The complete agenda is as follows:

    • "Diving into the Science of Biologics and Biosimilars: What Counsel Needs to Know to Formulate a Regulatory and Patent Strategy"
    • "Understanding the Structure of the USFDA and Its Role in Approving and Regulating Biosimilars"
    • "Delving into the Mechanics of the USFDA Biosimilars Approval Process and Section 351(k) Applications Under the Pathway"
    • "Mastering the Essentials of New USPTO Post-Grant Proceedings for Effective Use in the Biosimilars Space"
    • "Obtaining Adequate Patent Protection in the U.S.: Factoring Key Cases into Your Biosimilars Patent Strategy"
    • "U.S. Federal Trade Commission and State Law Updates: Understanding the Controversy Surrounding Competition, Substitution, and Naming in the Biosimilars Arena"
    • "Minimizing the Uncertainty Surrounding the Pathway: Insights Into USFDA's Current Initiatives Regarding the First Wave of Biosimilars Applications"
    • "Evaluating the Risk and Commercial Opportunity in the Emerging U.S. Biosimilars Landscape"
    • "In-House Keynote Address" by Julia Pike, Head Global IP Litigation for Sandoz
    • "Timing is Everything: A Cheat Sheet for Managing the Logistics of the BPCIA Exchange Process"
    • "Biosimilars Litigation Spotlight: Immediate Action Plans for Innovators and Biosimilars to Prepare for the Battles to Come"
    • "Incorporating Inter-Partes Review and New USPTO Procedures Into Branded and Biosimilar Litigation Strategies"
    • "Open Floor Session: Lessons Learned So Far: Comparing and Contrasting the U.S. and E.U. Biosimilars Experience"

    Orange Book Blog readers can save €100 with discount code OBB100.  For more information or to register, please visit the conference website.

  • Case or Controversy Exists Where Generic Manufacturer Seeks Declaratory Judgment of Non-Infringement of Orange Book-Listed Patent Disclaimed by Brand Manufacturer

    Apotex Inc. v. Daiichi Sankyo, Inc., Nos. 2014-1282, 2014-1291 (Fed. Cir. Mar. 31, 2015)

        by Dunstan H. Barnes

    Apotex, Inc. sued Daiichi Sankyo Co., Ltd. and Daiichi Sankyo, Inc. in the United States District Court for the Northern District of Illinois for a declaratory judgment of non-infringement of a Daiichi-owned, but Daiichi-disclaimed, patent, if Apotex were to manufacture or sell a generic drug bioequivalent of Daiichi’s Benicar®. On March 31, 2015, a three-judge Federal Circuit panel unanimously reversed the district court’s dismissal for lack of case of controversy. The Federal Circuit found that Apotex has a concrete, potentially high-value stake in obtaining a declaratory judgment, and that both Daiichi and generic manufacturer Mylan Pharmaceuticals, Inc. have a concrete, potentially high-value stake in denying Apotex that judgment and thereby delaying Apotex’s market entry.

    The factual background is key to understanding the debate. Daiichi listed two patents covering Benicar® in the Orange Book. The first, U.S. Patent No. 5,616,599, covers the active ingredient of the drug, and expires on April 25, 2016. Because Daiichi provided the FDA with pediatric test results, the FDA must wait a further six months, until October 25, 2016, to approve a generic version of the drug. The second, U.S. Patent No. 6,878,703, covers methods of treatment, and expires on November 19, 2021.

    In April 2006, Mylan filed an ANDA with a paragraph IV certification that both the ’599 and ’703 patents were invalid or not infringed by Mylan’s proposed generic drug. In July 2006, for reasons that remain unexplained, Daiichi disclaimed all claims of the ’703 patent, as permitted under 35 U.S.C. § 253. Daiichi then sued Mylan for infringing the ’599 patent. Only validity was disputed in the case, and after trial, the court upheld the validity of the ’599 patent and entered judgment of infringement against Mylan. With the validity of the ’599 patent intact, Mylan’s earliest date for market entry is October 26, 2016, six months after the ’599 patent expires. Note that as a result of the court’s decision, Mylan did not have a lawfully-maintained paragraph IV certification with respect to the ’599 patent.

    In June 2012, Apotex filed its own ANDA with a paragraph III certification stating that the ’599 patent is valid and a paragraph IV certification that Apotex would not infringe the now-disclaimed ’703 patent. Essentially, Apotex sought approval to enter the market for generic versions of Benicar® at the same time as Mylan—on October 26, 2016.

    The wrinkle is that Daiichi did not sue Apotex for infringing the disclaimed ’703 patent, and the FDA has not removed the ’703 patent from the Orange Book. Under § 355(j)(5)(B)(iv), because Mylan was the first ANDA filer and Mylan has lawfully maintained a paragraph IV certification regarding the ’703 patent, Mylan is presumptively entitled to 180 days’ exclusivity before facing competition from another generic manufacturer. Thus, if Mylan were to enter the market for generic version of Benicar® on October 26, 2016, it would presumptively be entitled to exclusivity until April 23, 2017.

    By filing its declaratory judgment action, Apotex sought to enforce a provision provided in § 355(j)(5)(D)(i)(I)(bb)(AA) for forfeiture of Mylan’s 180-day exclusivity period if Mylan has not marketed its generic drug 75 days after a court has entered a final decision from which no appeal (certiorari aside) has been or can be taken that the ’703 patent is invalid or not infringed.

    The parties did not dispute that allowing Apotex to enter the market earlier would likely transfer sales from Daiichi and Mylan to Apotex. But Daiichi maintained that there was no case or controversy because it could not assert its disclaimed ’703 patent against Apotex, and Mylan additionally argued that Apotex lacks a “tentative approval” from the FDA for its ANDA and thus any delayed-market-entry injury is unduly speculative.

    The Federal Circuit found, in contrast to the district court, that a case or controversy did exist, because the drug sales over a potential six-month period of exclusivity are concrete and substantial. The court contrasted the present parties’ substantial, concrete stakes in a judgment of non-infringement with cases in which a case or controversy was missing because the plaintiffs had generalized or bystander interest in others’ compliance with law.

    The Federal Circuit also provided a common sense reasoning regarding the fact that the now-disclaimed ’703 patent is the only barrier to Apotex entering the market at the same time as Mylan. Had Daiichi never listed the ’703 patent in the Orange Book, Mylan would not be eligible for an exclusivity period. Thus, Apotex seeks through its declaratory judgment action to eliminate the entry barrier created by Daiichi’s listing of the ’703 patent that Daiichi subsequently disclaimed.

  • ACI “Paragraph IV Disputes Master Symposium,” Chicago, September 30-October 1

    ACI's "Paragraph IV Disputes Master Symposium" returns to Chicago next week, September 30 to October 1.  According to ACI, this is an "advanced forum for brand name and generic counsel on the intricacies of Hatch-Waxman litigation."

    The agenda includes the following presentations:

    • Review of Key Supreme Court Cases that May Alter the Course of Paragraph IV Litigation
    • Identifying New Due Diligence Concerns Relative to ANDA Drug Targets and Anticipating New Paragraph IV Challenges
    • It's All About Timing:  Exploring the Surge in Premature Paragraph IV Notice Filings and Its Consequences
    • Teva v. Sandoz–A Debate on the Standard of Review for Claim Construction: De Novo vs. Deferential
    • Exploring the Use of Reissue Applications to Amend Invalidity Findings in the District Courts
    • Analyzing the Evolving Utilization of IPR and Other PTO Proceedings in Paragraph IV Litigation
    • Understanding the Importance of Abiding by Local Rules: A Magistrate's Perspective
    • A View from the Bench: The Judges Speak
    • Exploring New Developments in Double-Patenting Type Obviousness and Federal Circuit and PTO Discord on Obviousness
    • Experts, Problems of Proof, Dispositive Motions and Markman Hearings: Addressing Common Dilemmas Encountered in a Paragraph IV Trial
    • Understanding How the Supreme Court's Decision in Limelight v. Akamai Will Impact ANDA Litigation Involving Method of Treatment Patents
    • FTC Keynote: Reverse Payment Settlements and Other Antitrust Concerns Impacting Paragraph IV Litigation in the Wake of Actavis
    • The Ever Shifting Boundaries of the Safe Harbor: Determining the Scope of 271(e)(1) Protections Relative to Paragraph IV Litigation After Classen and Momenta
    • New Exclusivity Challenges for Brand Names and Generics: Exploring Their Implications for Paragraph IV Challenges
    • The Uncertain Future of At-Risk Launches: A Study of Injunctive Relief, Damages, and the Impact of the Protonix Case
    • Ethical Considerations for Paragraph IV Matters Before the PTO and District Courts

    ACI is also offering two pre-conference workshops on Monday, September 29:  "PTO Procedures Practice Boot Camp for Paragraph IV Litigators" and "A Judge's Perspective on Effectively and Ethically Communicating with the Court in Paragraph IV Matters," which will feature four former federal judges.

    Mention discount code OBB200 to save $200 on registration.  For more information, please visit the conference website.