Orange Book Blog

At the intersection of Patent and FDA Law

Recent Posts

  • After Court Victory over FDA, Teva Receives Final Approval of Risperidone ANDA and Launches With 180-Day Exclusivity

    Teva announced yesterday that the FDA granted final approval to its ANDA for generic Risperdal (risperidone) tablets, that it was awarded 180-day exclusivity as the first paragraph IV filer for risperidone, and that it immediately commenced a commercial launch.  FDA confirmed the final approval in a press release.  Risperdal is a schizophrenia drug marketed by Janssen, a unit of Johnson & Johnson, with annual U.S. sales of $2.8 billion.

    FDA’s decision to grant 180-day exclusivity to Teva follows an April 11, 2008, order of the U.S. District Court for the District of Columbia, granting Teva’s request to require FDA to relist Janssen’s U.S. Patent No. 5,158,952 in the Orange Book and enjoin FDA from approving any other risperidone ANDAs until Teva’s 180-day exclusivity period expires.

    Teva was the first ANDA applicant to file a paragraph IV certification on the ‘952 patent, but FDA delisted the patent in 2001, in response to a request from Janssen.  FDA argued to the district court that the ‘952 patent was delisted before Teva filed its ANDA.  Teva argued that the delisting “did not become effective until January 2002, when the official Orange Book reflected the delisting of that patent.”

    FDA has appealed the district court’s decision to the U.S. Court of Appeals for the D.C. Circuit, and oral argument is scheduled for September 12, 2008.  Meanwhile, according to the FDA website, risperidone ANDAs filed by Mylan and Pliva (a subsidiary of Barr Labs) have tentative approval.  Thus, if the D.C. Circuit reverses the district court, Teva’s 180-day exclusivity period would be cut short.

    RELATED READING:

  • Mutual Pharmaceutical Jumps the Gun By Sending Paragraph IV Notice Letter Before Acceptance of ANDA

    GlaxoSmithKline v. Mutual Pharm., No. 08-549 (E.D. Pa. 2008)

    The U.S. District Court for the Eastern District of Pennsylvania recently granted a motion for judgment on the pleadings in a paragraph IV case because the ANDA filer sent its notice letter prematurely, before FDA had accepted the ANDA for filing.  The case concerns Mutual Pharmaceutical’s generic version of GlaxoSmithKline’s heart medication Coreg CR (carvedilol phosphate).

    Mutual submitted its ANDA for carvedilol phosphate 80 mg capsules on November 19, 2007.  On December 21, Mutual filed an amendment to its ANDA, with a paragraph IV certification with respect to Glaxo’s U.S. Patent No. 7,268,156.  At the same time, Mutual sent Glaxo a paragraph IV notice letter, but FDA had not yet accepted Mutual’s ANDA at the time.

    On February 4, 2008 (the 45th day after receiving Mutual’s notice letter), Glaxo filed a complaint for declaratory judgment that, among other things, Mutual’s paragraph IV notice letter was “improper, null, void, and without legal effect.”  Mutual counterclaimed for a declaratory judgment that the ‘156 patent is invalid.  On March 17, following FDA’s acceptance of Mutual’s ANDA for filing, Mutual sent Glaxo a second notice letter.  The following day, Glaxo filed a motion for judgment on the pleadings.

    In opposition to Glaxo’s motion, Mutual argued that the relevant statute “says nothing that prohibits giving voluntary notice before the FDA has issued filing acceptance.”  According to the court, Mutual “seems to suggest that an ANDA applicant may send a Paragraph IV notice letter and thus trigger patent litigation, at any time it chooses.”

    In a decision on April 28th, however, the court concluded that “under the statute and regulations, the sending of a notice of a Paragraph IV certification is expressly predicated upon the ANDA applicant receiving its own notice and acknowledgment from the FDA that the submitted ANDA has been received.”  The court noted that the “Paragraph IV notice sequence ensures that the statutory litigation triggers do not result in unnecessary patent infringement litigation initiated by incomplete ANDAs.”  The court cited legislative history and FDA’s interpretation of the statute in support of its decision.

    Furthermore, the court rejected Mutual’s argument that even if the court dismissed Glaxo’s patent infringement claim without prejudice, it retained subject matter jurisdiction over Mutual’s counterclaim for a declaratory judgment of patent invalidity.  Here, the court contrasted the facts of the case with those of the Teva v. Novartis and Caraco v. Forest cases.  Additionally, the court reasoned that “due to the unfiled status of the ANDA, Defendants were not alleged infringers at the time this case was brought.”

    On April 30, Glaxo filed a second suit against Mutual, within the 45-day period from receipt of Mutual’s second notice letter.  Interestingly, on May 27, Mutual filed a Notice of Appeal of the district court’s decision on the first lawsuit.

  • FDA Denies King Pharma’s Citizen Petition Concerning Altace, Approves Ramipril ANDAs

    We reported last month that King Pharmaceuticals filed a citizen petition that could delay final approval of numerous ANDAs for generic versions of Altace (ramipril), which were set to earn final approval on June 7.  King's citizen petition asked FDA to require ANDA applicants for ramipril to file patent certifications with respect to newly-issued U.S. Patent No. 7,368,469, a method-of-use patent.

    On June 18, FDA denied King's citizen petition, concluding that the ANDAs may be approved with section viii "carve out" statements and that patent certifications are not necessary.  The same day, FDA granted final approval to the ANDAs.

    FDA's letter decision explains that King sought for FDA to

    confirm that label information describing cardiovascular outcomes from the Heart Outcomes Prevention Evaluation (HOPE) trial and the related indication may not be omitted from the labeling of any [ANDA or 505(b)(2) application] that relies upon an Altace product and seeks approval for treatment of hypertension.  Accordingly, the Petition seeks to confirm that ANDAs and 505(b)(2) applications that reference an Altace product must contain an appropriate patent certification to [the '469 patent] and may not contain a statement pursuant to section 505(b)(2)(B) or 505(j)(2)(A)(viii) of the Act explaining that the patent does not claim a use for which the applicant is seeking approval.

    FDA's letter concludes

    that ANDA and 505(b)(2) applicants seeking approval of ramipril products can omit from the product labeling the information from Altace labeling related to a reduction in risk of myocardial infarction, stroke, and death from cardiovascular causes (the HOPE indication) without rendering the proposed drug product less safe or effective than Altace products for the remaining conditions of use (treatment of hypertension and use in heart failure post-myocardial infarction).

    If FDA had reached the opposite conclusion and required ANDA applicants to include the HOPE indication in their labeling, the applicants would have had to file a paragraph III or IV certification to the '469 patent.  Although a paragraph IV certification would not have led to a 30-month stay of FDA approval (because the ANDAs had already been filed when King submitted the patent for listing in the Orange Book), such a certification would have allowed King to sue the applicant under 35 USC 271(e)(2) for infringement of the '469 patent.  Thus, the applicant would have had to decide whether to launch their generic ramipril product at-risk of liability for patent infringement.

    FDA's website shows that seven ramipril ANDAs were granted final approval immediately after FDA denied King's citizen petition and that Cobalt and Lupin also have final approval, for a total of nine generic ramipril products currently on the market.

  • Federal Circuit Refuses to Rehear Caraco v. Forest

    We previously reported that on April 1, in a 2-1 decision in Caraco v. Forest, the Federal Circuit held that an ANDA applicant may in some circumstances bring a declaratory judgment action for noninfringement even if the patentee has granted the applicant a covenant not to sue.  Today, the Federal Circuit denied Forest's petition for rehearing or rehearing en banc, without opinion.

    The Caraco v. Forest decision expanded declaratory judgment jurisdiction for ANDA applicants that have not been sued on an Orange Book-listed patent.  Indeed, several ANDA applicants have filed DJ complaints since the decision.

    It would not be surprising if Forest now appealed to the Supreme Court.  However, given that the Court recently decided a declaratory judgment case, MedImmune v. Genentech, and that the Federal Circuit appeared to follow that decision in Caraco v. Forest, Supreme Court review seems unlikely.

  • Mylan Prevails Over AstraZeneca in Appeal of Prilosec Case

    In re Omeprazole Patent Litigation, Nos. 2007-1476, -1477, -1478 (Fed. Cir. 2008)

    Yesterday, the Court of Appeals for the Federal Circuit affirmed a June 2007 district court decision finding that Mylan's generic version of Prilosec (omeprazole) does not infringe two AstraZeneca patents, U.S. Patent Nos. 4,786,505 and 4,853,230.

    Omeprazole is difficult to formulate because it is acid-labile.  Astra scientists developed a formulation that protects omeprazole from degradation in the acidic environment of the stomach.  Astra's formulation, which is claimed in the '505 and '230 patents, includes a core containing omeprazole and an alkaline reacting compound ("ARC"), a water soluble subcoat, and an outer enteric coating.

    Mylan's ANDA product consists of an inert sugar/starch sphere; an active coating of omeprazole, talc and HPMC; two subcoatings; and an enteric coating.  Astra argued that the talc in Mylan's formulation contains carbonates, which serve as an ARC.  However, after a forty-two day bench trial, the district court determined that Astra failed to prove the presence of carbonates in Mylan's product.  The district court also determined that talc cannot satisfy the ARC limitation of the claims because the specification of the patents indicates that talc is not an ARC but rather an ordinary excipient, and because of statements Astra made during prosecution of the European counterpart of the '505 patent.

    In the decision released yesterday, the Federal Circuit concluded that the district court's factual findings with respect to the presence or absence of carbonates in Mylan's formulation were not clearly erroneous.  Astra argued on appeal that the district court applied the wrong legal standard by requiring "conclusive evidence" that carbonates were present in the talc, but the Federal Circuit disagreed, finding that the district court correctly applied the preponderance of the evidence standard.  Having determined that the district court did not clearly err in finding that Astra failed to prove the presence of "non-negligible amounts of carbonates" in Mylan's formulation, the Federal Circuit declined to address Astra's remaining arguments.

    The omeprazole patent litigation began in 2000, when Astra sued several companies who filed ANDAs for generic Prilosec.  The lawsuits were consolidated as a multidistrict litigation and tried in two waves.  Mylan, which launched its generic Prilosec in August 2003, was part of the second wave.  Other companies in the second wave included Lek Pharmaceutical, Apotex, and Impax Labs.  In the same June 2007 decision in which it ruled in favor of Mylan, the district court also found that Lek's products do not infringe Astra's patents, and that Apotex's and Impax's products do infringe.  Those determinations were appealed separately.

    RELATED READING:

  • OBB News Briefs

    • The Federal Trade Commission announced the release of its FY 2007 Summary of Pharmaceutical Company Settlement Agreements.  For commentary, see FDA Law Blog, Pharmalot.
    • Wyeth sued Sandoz over a generic version of Protonix I.V.  The WSJ Health Blog recapped all the Protonix ANDA litigation.
    • India's drugmakers recently threatened to stop production of 33 bulk drugs, Pharmalot reports.
    • The Washington Legal Foundation announced that it filed an amicus brief urging the Federal Circuit to rehear the Caraco v. Forest Labs case.

  • C5 “Pharma Patent Lifecycles” Conference, London, June 26-27

    C5 will be holding a “Pharma Patent Lifecycles” conference June 26-27 in London.  According to C5, “since 2001, thousands of life sciences patent professionals have made C5’s Pharma Patent Lifecycles conferences their source of information for the most up-to-date legal developments surrounding patent lifecycle management.”

    The agenda includes numerous presentations that may be of interest to readers:

    • “Critical Update on European Case Law and Legislative Developments”
    • “The Impact of Regulatory Data Protection on Lifecycle Management”
    • “Recent Trends and Developments in Supplementary Protection Certificates and Paediatric Extensions”
    • “Successful Evergreening Strategies to Compete with Generics and Obtain PC’s”
    • “Effective Use of Second Medical Use (Swiss-Type) Claims to Extend Patent Lifecycles”
    • “Brand Name and Generic Litigation as a Defence or Delay Tactic?  UK and US Comparative”
    • “How to Optimise Your Product’s Lifecycle Through Successful Global Patent Lifecycle Management”
    • “Industry Case Study and Break Out Session: Insight into Pfizer’s European Lipitor Litigation”

    In addition, a pre-conference master class is offered on June 25: “Patent Settlements Master Class: A Step-by-Step Guide to Meeting EU Anti-Competition Law Guidelines.”

    For more information or to register, please visit the conference website.

  • King Pharmaceuticals Files Citizen Petition Relating to New Patent on Altace (Ramipril)

    King Pharmaceuticals markets Altace (ramipril), which is indicated for the treatment of high blood pressure.  Until last year, when the Federal Circuit invalidated King's compound patent on ramipril, King earned about $700 million annually from U.S. sales of Altace.

    Although Lupin was the ANDA filer who prevailed against King in the patent litigation, Cobalt Labs, as the first ANDA filer, won the 180-day exclusivity rights.  In a letter dated January 29, 2008, to attorneys for Lupin, FDA explained that Cobalt's exclusivity was triggered on December 10, 2007, and will expire on June 7, 2008.

    Recently, on May 16, 2008, King submitted a citizen petition requesting that FDA require ANDA applicants for generic ramipril to submit a paragraph III or IV certification to U.S. Patent No. 7,368,469, which issued May 6, 2008, prior to final approval.  The '469 patent claims methods "for reducing the risk of a cardiovascular event" by administering an ACE inhibitor such as ramipril.

    According to the FDA website, at least seven ANDA filers have tentative approval for ramipril and thus appear to have planned on obtaining final approval on June 7, when Cobalt's 180-day exclusivity expires.  Those plans may now be in doubt, as it may take FDA some time to decide how to rule on King's petition.

    RELATED READING:

  • Patent Litigation Under a Future Biosimilars Act

        Biopharmaceuticals, such as Epogen® (epoetin) and Erbitux® (cetuximab), are becoming increasingly important for the treatment of disease.  U.S. sales of such drugs were about $40 billion in 2006 and are expected to rise to over $90 billion in 2009.  Accordingly, political pressure is building to allow the sale of “biosimilar” drugs.  Inspired by the success of the Hatch-Waxman Act, which has led to the wide use of generic “small molecule” drugs, four different biosimilars bills have been introduced in Congress in the past fifteen months.  Three of the proposed bills would establish a complex scheme for patent litigation between brand-name and generic biopharmaceutical companies, especially as compared to the Hatch-Waxman Act.

    Hatch-Waxman Act

        The Hatch-Waxman Act, passed by Congress in 1984, amended the Food, Drugs and Cosmetic Act to establish an abbreviated pathway for FDA approval of small molecule drugs.  Under the Act, a company seeking to market a generic small molecule drug must demonstrate only that the generic is “bioequivalent” to the corresponding brand-name drug; it need not conduct large scale clinical trials demonstrating safety and efficacy.  The Hatch-Waxman Act, however, did not amend the Public Health Service Act, under which biopharmaceuticals are approved, and therefore it did not create an abbreviated pathway for the approval of biopharmaceuticals.
        The Hatch-Waxman Act established a relatively straightforward scheme for patent litigation.  In a New Drug Application, a brand-name drug company is required to inform the FDA of any patents claiming the drug or methods of using the drug “with respect to which a claim of patent infringement could reasonably be asserted.”  The patent information is listed in the FDA’s “Orange Book,” which the FDA updates regularly and publishes on the Internet.  When a generic drug company submits an Abbreviated New Drug Application (“ANDA”), it is required to file one of four different patent certifications with respect to any patents listed in the Orange Book for the brand-name drug.  Upon filing a Paragraph IV certification (indicating that a listed patent is invalid, unenforceable, or not infringed), the generic drug company is required to provide notice to the patent owner.  If the patent owner brings suit within 45 days of receiving notice, then the FDA may not grant final approval of the ANDA for 30 months.  This last feature – the automatic 30-month stay – is conspicuously absent from all of the proposed biosimilars bills.

    Access to Life-Saving Medicine Act

        Rep. Henry Waxman introduced the first of the four biosimilars bills, the Access to Life-Saving Medicine Act (H.R. 1038), on February 14, 2007.  The Waxman bill is regarded as the one most favorable to the generic drug industry.  It establishes a complicated system for the private exchange of patent information between brand-name and generic biopharmaceutical companies, and contains unusual provisions regarding patent litigation.

    (more…)

  • OBB News Briefs

    • As reported by FDA Law Blog, FDA determined on May 7 that Cobalt forfeited its 180-day exclusivity on acarbose and Cobalt sued FDA on May 8 for injunctive relief.  Last Friday, for some reason, Cobalt voluntarily dismissed its suit against FDA.
    • Also last Friday, FDA appealed the D.C. district court’s decision requiring relisting of Janssen’s patent on Risperdal (risperidone).
    • Ivax recently filed a declaratory judgment complaint against AstraZeneca, reportedly seeking to trigger Ranbaxy’s 180-day exclusivity on esomeprazole.  AstraZeneca and Ranbaxy settled their esomeprazole litigation last month.
    • The district court in Washington, D.C. recently transfered the FTC v. Cephalon "reverse payment" antitrust case to the Eastern District of Pennsylvania, Reuters reported, possibly throwing a wrench into the FTC’s plans to get a "reverse payment" case before the Supreme Court.
    • Pharmalot had an interesting post last week on the coming wave of generic drugs from Chinese generic drug companies.