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At the intersection of Patent and FDA Law

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  • Federal Circuit Affirms Obviousness of Novo Nordisk’s PRANDIN Patent

    Novo Nordisk v. Caraco Pharm. Labs., No. 2011-1223 (Fed. Cir.)

    In its third trip to the Federal Circuit, the court on Tuesday affirmed a decision holding claim 4 of Novo's U.S. Patent No. 6,677,358 invalid as obvious.  Claim 4 of the '358 patent, listed in the Orange Book for PRANDIN (repaglinide) tablets, is directed to "[a] method for treating non-insulin dependent diabetes mellitus (NIDDM) comprising administering to a patient in need of such treatment repaglinide in combination with metformin."  This is the same case in which the Supreme Court decided last year that a "delisting counterclaim" may be used to force amendment of an Orange Book use code.

    The Federal Circuit's opinion on Tuesday was authored by Judge Prost and joined by Judge Dyk.  Judge Newman dissented in a pointed opinion.  The court also unanimously reversed the district court's finding that the '358 patent is unenforceable due to inequitable conduct.

    The case revolved around the three bases that Novo advanced for reversal of the district court's finding of obviousness–two of which (incorrect burden shifting to the patentee and lack of deferral to fact-finding by the USPTO) were quickly dispatched by the court.  But on the third basis for reversal–that Caraco's evidence insufficiently supported the district court's ultimate obviousness finding, the judges divided sharply on their interpretation of the record.

    The majority based its affirmance of obviousness on the district court's reasoning that:

    1. the closest prior art [to the repaglinide/metformin combination] was combination therapy using metformin and a sulfonylurea;

    2. combination therapy using metformin and one of the sulfonylurea class of secretagogues was well known in the art to produce beneficial and even synergistic results in controlling glucose levels in Type II diabetes patients; [and]

    3. repaglinide was known as an insulin secretagogue having a similar mechanism of action to the sulfonylurea class of secretagogues.

    These findings outweighed Novo's evidence, both before the USPTO and during litigation, that the combination of repaglinide and metformin is, unexpectedly, eight times more effective in reducing fasting plasma glucose ("FPG") levels than metformin alone and despite repaglinide having no impact on FPG.

    The majority explained away the allegedly unexpected effect of repaglinide/metformin on FPG by noting that "[r]epaglinide and sulfonylureas are both insulin secretagogues, and they therefore have a 'similar mechanism of action'" and that "the prior art taught that metformin could be combined with certain sulfonylureas which were, like repaglinide, short-acting secretagogues."  In particular, the court noted that prior art proffered by Caraco "report[ed] that metformin/sulfonylurea combinations yielded an 'apparent synergistic effect' and 'appear[ed] to have a synergistic effect'."

    The court further picked apart Novo's evidence of unexpected results by noting that (1) the same study that found the reduction in FPG (the "Moses Study"), also showed that the near-term and long-term benefits of repaglinide/metformin "were generally inferior to the results found by prior art studies involving metformin combined with sulfonylureas"; (2) Novo's expert, Dr. Sturis, felt that the Moses Study had not mathematically or scientifically proven the existence of synergy; (3) Dr Sturis' own repaglinide/metformin study only "strongly suggest[ed]" synergy; (4) Novo's final study (Pfeiffer), showing a 35% improvement in insulin sensitivity in repaglinide/metformin combination therapy over metformin alone, had questionable reliability due to its small sample size, or results that were "explained away" by Pfeiffer in a contemporaneous report as predictable in view of the prior art; and (5) certain other tests on drug-naïve patients either did not "consistently" show a synergistic effect on FPG or did not "show statistically better results than the drugs used in monotherapy."

    On these bases, the court concluded that "it is reasonable that an artisan seeking to combine a known insulin sensitizer (like metformin) with a new insulin secretagogue (like repaglinide) would base his expectations upon prior art sensitizer/secretagogue combinations."  In fact, the Court found that it was "not erroneous . . . to conclud that the prior art predicted the results" of the combination of repaglinide and metformin on FPG.

    Judge Newman begged to differ from her colleagues' "erroneous view of the evidence and incorrect application of the law of obviousness."  In her view, the panel majority's generalization that "earlier metformin/sulfonylurea combinations were generally understood to yield synergy," was inaccurate.  Rather, only some sulfonylureas formed synergistic combinations, but "synergism was not a general property of the combinations."  According to Judge Newman, "it was well-known that not all insulin stimulants form synergistic combinations with metformin."

    Focusing on the district court's selection of the combination of metformin-glyburide to invalidate the '358 patent, Judge Newman noted the substantial differences between repaglinide and glyburide, including the substantial structural differences between the two and the fact that the latter is a long-lasting insulin secretagogue while repaglinide is a short-lasting secretagogue.  In order to provide a more equal comparison from which to draw reasonable expectations, Judge Newman suggested that "a more reasonable analysis would consider metformin in combination with nateglinide, which is structurally similar to repaglinide, or a shorter-acting sulfonylurea such as glipizide."  That is, "the 'closest prior art' is the reference having the most 'in common' with the claimed invention, not the reference that happens to describe the most impressive results."

    Reacting to the majority's dissection of Novo's evidence of unexpected results, Judge Newman reminded the majority that, "[t]o be patentable, a compound need not excel over prior art compounds in all common properties."  Rather, one must look to whether the claimed combination "would produce results superior to the additive effect of the components separately."  On a record where it was not shown that glyburide was an effective synergist in combination with metformin, Judge Newman could not conclude that repaglinide would be expected to be an effective synergist.  Ultimately, for Judge Newman, "[t]he synergy demonstrated by Novo for the metformin-repaglinide combination therapy was not predicted or predictable, and was not obvious."

  • Supreme Court Decides That “Reverse Payment” Settlements Shall be Subjected to “Rule of Reason” Antitrust Analysis

    Federal Trade Comm'n v. Actavis, Inc., 570 U.S. ____ (2013)

        by Aaron F. Barkoff

    The U.S. Supreme Court, in a 5-3 opinion, decided today that "reverse payment" settlements of ANDA litigation shall be analyzed according to the "rule of reason."  Thus, the Court compromised between the positions urged by the parties: that such settlements are presumptively illegal (FTC) or that they are virtually immune from antitrust scrutiny (Actavis).

    The case arose from ANDA litigation between Solvay and Actavis over a generic version of Solvay's AndroGel product.  The parties settled the case in 2006, agreeing that Solvay would pay Actavis $19-30 million annually until 2015, when Actavis would be permitted to market its generic product (5+ years before Solvay's patent expired).  In addition, Actavis agreed to promote AndroGel to urologists.

    The FTC sued the parties in 2009, alleging that they unlawfully agreed "to share in Solvay's monopoly profits, abandon their patent challenges, and refrain from launching their low-cost generic products to compete with AndroGel for nine years."  The U.S. District Court for the Northern District of Georgia dismissed the FTC's complaint, holding that the allegations did not set forth an antitrust violation.  The 11th Circuit affirmed the dismissal, writing that "absent sham litigation or fraud in obtaining the patent, a reverse payment settlement is immune from antitrust attack so long as its anticompetitive effects fall within the scope of the exclusionary potential of the patent."

    In affirming the dismissal of the FTC's complaint, the 11th Circuit applied the so-called "scope of the patent test," which looks primarily at whether the agreed-upon generic entry date is later than the expiration date of the patent.  Under this test, according to critics, reverse payment settlements are virtually immune to the antitrust laws.  Other circuits applying the "scope of the patent" test include the Federal Circuit (Ciprofloxacin) and 2nd Circuit (Tamoxifen).  The 3rd Circuit, on the other hand, held in the K-Dur case last year that the appropriate test is the "quick look," under which reverse payment settlements are presumptively illegal.  The Supreme Court took this case to resolve the circuit split.

    Writing for the majority, Justice Breyer summarized the Court's opinion as follows:

    In sum, a reverse payment, where large and unjustified, can bring with it the risk of significant anticompetitive effects; one who makes such a payment may be unable to explain and to justify it; such a firm or individual may well possess market power derived from the patent; a court, by examining the size of the payment, may well be able to assess its likely anticompetitive effects along with its potential justifications without litigating the validity of the patent; and parties may well find ways to settle patent disputes without the use of reverse payments.  In our view, these considerations, taken together, outweigh the single strong consideration–the desirability of settlements–that led the Eleventh Circuit to provide near-automatic antitrust immunity to reverse payment settlements.

    The Court's opinion suggests a few ways in which ANDA litigants can settle their cases without raising antitrust concerns.  First, as the FTC has stated, the parties can settle simply by compromising on a generic entry date that is somewhat earlier than the patent expiration date–without any payment.  But the Court also suggested that even certain settlements including a payment will survive a rule of reason analysis:

    Where a reverse payment reflects traditional settlement considerations, such as avoided litigation costs or fair value for services, there is not the same concern that a patentee is using its monopoly profits to avoid the risk of patent invalidation or a finding of noninfringement.  In such cases, the parties may have provided for a reverse payment without having sought or brought about the anticompetitive consequences we mentioned above.  But that possibility does not justify dismissing the FTC's complaint.  An antitrust defendant may show in the antitrust proceeding that legitimate justifications are present, thereby explaining the presence of the challenged term and showing the lawfulness of that term under the rule of reason.

    Chief Justice Roberts, joined by Justices Scalia and Thomas, would have affirmed the 11th Circuit and upheld the "scope of the patent" test.  In dissent, he wrote:

    The majority points to no case where a patent settlement was subject to antitrust scrutiny merely because the validity of the patent was uncertain.  Not one.  It is remarkable, and surely worth something, that in the 123 years since the Sherman Act was passed, we have never let antitrust law cross that Rubicon.

    Also today, the Court scheduled a June 20 conference to discuss the cert petition in K-Dur.  Presumably, the Court will issue a "GVR," granting the petition, vacating the 3rd Circuit opinion, and remanding the case to the 3rd Circuit for analysis under the rule of reason.

    RELATED READING:

  • Supreme Court Holds That Isolation of DNA Does Not Confer Patent Eligibility Under 35 U.S.C. § 101

    Ass'n for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. ____ (2013)

        by Christopher P. Singer

    "We merely hold that genes and the information they encode are not patent eligible under § 101 simply because they have been isolated from the surrounding genetic material."  –Thomas, J.

    On June 13, 2013, the U.S. Supreme Court handed down its decision in Association for Molecular Pathology v. Myriad Genetics.  In the opinion, authored by Justice Thomas, the Court unanimously held that "[a] naturally occurring DNA segment is a product of nature and not patent eligible merely because it has been isolated."  The Court also held that because cDNA is not a product of nature and does not face the same patent eligibility hurdles as naturally occuring isolated DNA, typically it is eligible for patenting.

    Isolated DNA

    Myriad owns the patents containing the claims at issue in
    this case, which are directed to isolated DNAs and cDNAs covering the human
    genes BRCA1 and BRCA2, as well as certain mutations in those genes that are
    indicative of an increased risk of developing breast or ovarian cancer.  Much of the opinion focuses on
    why the "mere isolation" of DNA from the genome is not adequate to make even
    newly formed and non-naturally occurring DNA molecules patent eligible.  Though the Court acknowledges that the
    identification and discovery of the precise location of the BRCA1 and BRCA2
    genes was important and useful, it swiftly concludes that the subsequent
    isolation of that genetic material failed to create something that constitutes
    an act of invention.  It states that
    "[t]he location and order of the nucleotides existed in nature before Myriad
    found them" and that Myriad did not "create or alter the genetic structure of
    DNA."  The Court then relies on its prior
    decisions in Diamond v. Chakrabarty, 447 U.S. 303 (1980), and Funk Brothers Seed
    Co. v. Kalo Inoculant Co.    , 33 U.S. 127 (1948), to conclude that Myriad's
    "discovery, by itself, does not render the BRCA genes 'new . . . composition[s]
    of matter,' . . . that are patent eligible."  (Slip Op. at 12-13).

    The opinion directly addresses and rejects the rationale
    articulated by the Federal Circuit when it held that the breaking of chemical
    bonds in the process of isolating DNA from the genome can create a chemical
    moiety that did not previously exist in nature:

    Nor are Myriad's claims saved by the fact that isolating
    DNA from the human genome severs chemical bonds and thereby creates a nonnaturally
    occurring molecule.  Myriad's claims are
    simply not expressed in terms of chemical composition, nor do they rely in any
    way on the chemical changes that result from the isolation of a particular
    section of DNA.  Instead, the claims
    understandably focus on the genetic information encoded in the BRCA1 and BRCA2
    genes.

    (Slip Op. at 14-15).

    The beginning of the passage is a bit puzzling–because DNA is a chemical composition regardless of whether it is described as "GATC" or "a polymer comprising a series of alternating phosphate groups and deoxyguanosine, deoxyadenosine, deoxythymidine, or deoxycytidine monomers having
    the sequence . . . ."  But the end of the passage clarifies that the Court considers the
    significance of the claimed DNA to relate to the information it contains, and that the
    differences in chemical structure between isolated and genomic DNA is
    inconsequential to patentability under § 101.

    The Court also dismissed the notion that it should give
    any deference to the 30+ years of USPTO practice granting patents directed
    to isolated genes, particularly because the U.S. Solicitor General argued that the
    Patent Office should not grant patents directed to genes.

    cDNA

    In its relatively brief analysis of the patent
    eligibility of cDNA molecules, the Court explains the difference it perceives
    between isolated genomic DNA and cDNA, stating that "creation of a cDNA
    sequence from mRNA results in an exons-only molecule that is not naturally
    occurring."  Thus, a DNA sequence that is
    created in a lab and contains only the protein coding portion of the genomic
    sequence is adequate to meet the eligibility requirements of § 101.  The Court addressed AMP's argument that cDNA
    should be held ineligible because the sequence of cDNA is determined by portions of
    the underlying gene sequence–not by an inventor.  The Court rejected that argument, stating
    that even though cDNA retains naturally occurring exons, it is distinct from
    the genomic DNA from which it was derived and therefore not a product of nature.

    Do Genetically Engineered DNA Molecules Provide a Path Forward?

    While the Court chose not to express any opinion about
    whether genetically engineered DNA molecules are patent eligible, the opinion
    suggests a simple dispositive question for determining DNA patent
    eligibility under § 101: Is the sequence
    of a claimed DNA molecule (i.e., informational component) the same as the
    sequence information as it exists in nature? 
    If the answer is yes, then the claimed DNA fails to meet the
    requirements of § 101.  This analysis
    would seem to fit within the Court’s concluding statement and caveat concerning
    cDNA at the end of Section II of the opinion:

    cDNA retains the naturally occurring exons of DNA, but it
    is distinct from the DNA from which it was derived.  As a result, cDNA is not a
    "product of nature" and is patent eligible under § 101, except insofar as very
    short series of DNA may have no intervening introns to remove when creating
    cDNA.  In that situation, a short strand of cDNA may be indistinguishable from
    natural DNA    .

    (Slip. Op. at 17,
    emphasis added). 

    This seems to indicate that the Court views
    cDNA as patent eligible only if it includes at
    least two exons that are not directly adjacent to each other in the
    genomic sequence. 
    However, if the claimed cDNA sequence–or any engineered DNA sequence
    for that matter–can be mapped directly to a naturally occurring DNA sequence,
    the claim will fail to satisfy § 101.  While
    this test has almost the exact flavor of a novelty and nonobviousness analysis
    under 35 U.S.C. §§ 102 and 103, this type of § 101 analytical framework would not
    be surprising, considering that these statutory provisions have crept into the
    Court’s recent § 101 decisions (e.g., Mayo v. Prometheus).

    The Patent Office has already issued a memorandum to the examining corps that directs
    examiners to begin issuing rejections under § 101 for claims to any naturally
    occurring nucleic acid sequences or fragments thereof.  In some ways, however, this procedure may not
    place much additional burden upon the examiners, as the Office already performs
    sequence database searches for claims directed to defined biological sequences
    (albeit for purposes of examination under § 102 and § 103).  The question may turn on whether examiners or
    applicants bear the burden of demonstrating that the claimed sequence is
    actually "naturally occurring" (barred by § 101) or simply just present in the
    prior art (eligible under § 101, but allegedly obvious under § 103).  It will be interesting to see how the Patent Office develops additional guidelines and guidance documents in the wake of this decision.

    The impact of this decision may not become apparent for some
    time.  Certainly, it does mark a
    significant change to the examination of claims directed to nucleic acid
    sequences; however, many diagnostics and biotechnology companies do not rely
    exclusively on patents to isolated nucleic acid sequences.  As long as claims to nucleic acid sequences
    are sufficiently tailored to avoid reading on a naturally occurring sequence,
    the Court’s decision provides room to continue to pursue patents directed to
    compositions of matter that include expression vectors, therapeutic nucleic
    acids, enzymatic nucleic acids, and chemically modified probes.

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  • ACI “4th Advanced Forum on Biosimilars,” New York City, June 5-7

    ACI will be holding its "4th Advanced Forum on Biosimilars" in New York City on June 5-7.  McAndrews, Held & Malloy partner Sandra Frantzen will be speaking on the written description and enablement requirements for biologics patents.  The full agenda includes the following presentations:

    • The Biosimilars Pipeline: Evaluating the Commercial Opportunity and Viability of Follow-On Products
    • Overcoming the Complicated Challenges to Establishing Biosimilarity
    • The Next Fronteir of Biosimilars Challenges: Naming and Substitution at the Pharmacy Level
    • Two Roads Diverged in a Wood: Evaluating Whether to Go Down the Biosimilars or BLA Pathway
    • In-House Keynote: Interchange or "Out of Change"–the Changing World of Biosimilars
    • In-House Roundtable Debate: Companies Weigh in on the Abbreviated Pathway
    • The Reality of the Market: Lessons Learned So Far from Global Biosimilars Development and Litigation
    • Preparing for the Impending Reality of Biosimilars Patent Litigation: Immediate Action Plans for the First Wave
    • The Post-AIA World: Revolutionizing Biosimilars Litigation Strategies in Light of Validity Assessment at the PTO
    • Practical Claim Drafting and Patent Prosecution Strategies for Biosimilars and Innovators
    • Exploring Opportunities to Strengthen Your Patent Portfolio Through Licensing
    • The Use of Citizen Petitions in the Biosimilars Context: A Case Study of AbbVie's Petition
    • Evaluating the Benefit of Trade Secret Protection Versus Patent Protection: Alternative Ways to Protect Biologic and Biosimilar Technology
    • Navigating Tricky Confidentiality and Conflicts Issues in the New Biosimilars Exchange Process

    In addition, two pre-conference workshops will take place on June 5: "Biologics 101: Translating the Underlying Science into a Strong Biosimilars Patent Portfolio Strategy" in the morning; and "Monoclonal Antibodies: Successful and Practical Strategies for Developing and Commercializing Antibody Therapies" in the afternoon.

    Orange Book Blog readers can receive discounted registration by using code OBB 200.  For additional information or to register, please visit the conference website.

  • ACI “Paragraph IV Disputes” Conference, New York City, May 7-8

    ACI will be holding its always-popular "Paragraph IV Disputes" conference in New York City next week, on May 7-8.  This year's conference–the 7th annual–looks better than ever.  The agenda includes the following presentations:

    • Anticipating a Paragraph IV Challenge: New Considerations in Light of AIA and the Patent Cliff
    • Asserting Invalidity or Non-infringement Under Paragraph IV: Exploring the ANDA Applicant's Pre-litigation Obligations and Options
    • Safe Harbor or Stormy Port?: Analyzing How New 271(e)(1) Controversies Will Impact Paragraph IV Disputes
    • Throwing Down the Gauntlet: The Paragraph IV Notice Letter
    • Obviousness in Retrospect: Making Sense of Prior Art, Obviousness-Type Double Patenting, Inherency and New AIA Controversies
    • Let the Games Begin: The Start of the Paragraph IV Law Suit — Pleadings and Other Considerations
    • A View From the Bench — with Hon. Paul R. Michel, Hon. Gregory M. Sleet, Hon. Stanley R. Chesler, Hon. Joel A. Pisano, Hon. Tonianne Bongiovvani, and Hon. Garrett E. Brown
    • Pay-for-Delay Update — presented by Markus H. Meier, Asst. Dir., Health Care Division, Bureau of Competition, Federal Trade Commission
    • Settlement of Paragraph IV Law Suits: The Industry Perspective
    • Parallel and Alternate Proceedings in Paragraph IV Disputes: Seeking Simultaneous or Sole Redress Before the PTO, ITC and Other Alternative Forums — with Hon. Garrett E. Brown, Mon. Mary Pat Thynge, Hon. Joseph A. Dickson, Hon. James Donald Smith, and Hon. Robert K. Rogers
    • FDA Proceedings and Regulatory Developments Impacting Paragraph IV Litigation
    • New Exclusivity Challenges: Brand Names Take Notice — It's Not Just a Concern for Generics Anymore
    • Examining New Rulings in Inducement of Infringement and Divided Infringement and Their Application to Method Claims in Hatch-Waxman Litigation
    • New Developments in Damages Theories and Injunctions Relative to At-Risk Launches: Legal and Economic Assessments
    • Inequitable Conduct Developments in the Courts and at the PTO: Ethical Considerations for Paragraph IV Cases

    In addition to the main conference, ACI is offering two pre-conference workshops on May 6.  In the morning will be Hatch-Waxman and BPCIA 101 — A Primer on IP Basics and Regulatory Fundamentals; and in the afternoon, Working Group Session: Assessing the Impact of New PTO Procedures Under the AIA on Paragraph IV Litigation.  Finally, on May 9 ACI is offering a post-conference Master Class on Settling Paragraph IV Disputes: Drafting and Negotiating Strategies for Brand Names and Generics — A Hands-On, Practical Approach.

    Orange Book Blog readers are eligible for a discounted registration rate by using code OBB 200.  For additional information or to register, please visit the conference website.

  • “Defective” Complaint Triggers 30-Month Stay

    Endo Pharmaceuticals v. Mylan, No. 11-220-GMS (D. Del.)

    In an opinion filed on Monday, the U.S. District Court for the District of Delaware granted leave to Endo Pharmaceuticals to file an amended complaint to
    correct a defective initial complaint. 
    In doing so, the court found that Endo's first complaint, while
    defective, properly triggered a statutory thirty-month stay.

    On January 28, 2011, Endo received a Paragraph IV notice letter from Mylan concerning generic LIDODERM (lidocaine patch 5%) and asserting that U.S. Patent No. 5,741,510 is invalid or not infringed. 
    According to Endo, LecTec Corp. (not Endo)
    was the owner of the '510 patent at the time.  On
    March 14, 2011, Endo filed a complaint alleging that (1) Mylan failed to comply
    with the statutory requirements because it failed to notify the patent owner, LecTec (Count 1); and (2) "if the court
    determines now or at a future date that Mylan has complied with its obligations
    under the Hatch-Waxman Act to provide valid notice" then Endo pleads in the
    alternative that Mylan infringed the '510 patent by submitting its ANDA (Count
    2).

    In an order dated March 30, 2012, in response to a motion to dismiss from Mylan, the court dismissed
    Endo's complaint because: (1) Endo lacked standing to challenge Mylan's
    compliance with the statutory notice provisions; and (2) the court could not reach the infringement claim of Count 2 because Endo phrased
    Count 2 to be conditioned on a determination concerning Count 1.

    Endo moved for leave to amend its initial complaint, arguing that
    the conditional language in Count 2 of the complaint was a technical
    defect in pleading.  In its opinion Monday, granting Endo's motion, the court found that
    Endo did not unreasonably delay in filing its motion and that Mylan would not
    suffer undue prejudice as a result of the amended complaint.

    In addition, the court rejected Mylan's
    argument that the amended complaint could not relate back to the initial
    complaint under Fed. R. Civ. P. 15(c). 
    Mylan had argued that the statutory 45-day time period to invoke a 30-month stay is akin to a statute of limitations, and therefore Endo's
    initial complaint should be treated as if it never existed and "should not be
    allowed to anchor a thirty-month stay."  In response, the court first noted that
    the 45-day time period for filing suit under the Hatch-Waxman Act is not
    properly characterized as a statute of limitations because failure to file suit
    within the 45-day window does not bar an infringement action.  The court further stated, "While Endo's
    complaint suffered from certain pleading defects, there is no dispute that it
    was brought within the forty-five day timeframe, and, despite its pleading
    defect, the court believes it represents 'an action . . . brought for infringement of
    the patent that is the subject of the certification' within the meaning of the
    statutory language."

    Losing this argument, however, does not appear to be a great loss for Mylan, since the thirty-month stay runs from January 28, 2011, and so will expire just four and a half months from now.

  • District of New Jersey Considers Subject Matter Jurisdiction Where No Paragraph IV Certification Is Filed

    Merck Sharp & Dohme Corp. v. Sandoz Inc., No. 12-3289 (D.N.J. 2013)

        by Katherine H. Johnson

    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)."

  • Federal Circuit Addresses Sufficiency of Factual Support Needed to Show Undue Experimentation

    Cephalon, Inc. v. Watson Pharms., Inc., No. 2011-1325 (Fed. Cir. 2013)

        by Katherine H. Johnson

    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. 

  • Momenta Pharmaceuticals Files Supreme Court Petition in 271(e)(1) Safe Harbor Case

        by Aaron F. Barkoff

    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."

    In Momenta, the patent owner accused its competitors of infringing patents claiming methods of analyzing enoxaparin.  More specifically, Momenta argued that the defendants' post-approval testing of commercial batches of enoxaparin infringed its patent.  The defendants, on the other hand, argued that their activities were reasonably related to the FDA requirement to perform quality-control testing on commercial batches of their product, and were therefore protected by the safe harbor.  This time, in another 2-1 decision, the Federal Circuit found in favor of the defendants.  The majority distinguished Classen:

    Here, the submissions are not "routine submissions" to the FDA, but instead are submissions that are required to maintain FDA approval.  . . .  Unlike Classen, where the allegedly infringing activity "may" have eventually led to an FDA submission, there is no dispute in this case that Amphastar's allegedly infringing activities are carried out to "satisfy FDA's requirements."

    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.

    In its cert petition, Momenta frames the question presented as follows:

    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.

  • Federal Circuit Interprets ANDA Litigation Settlement Agreement

    Eurand v. Impax Labs., No. 2012-1280 (Fed. Cir.)   

        by Alex Menchaca

    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.