Orange Book Blog

At the intersection of Patent and FDA Law

Recent Posts

  • FDA Grants Baxter’s Petition for Second 30-Month Stay Relating to Suprane

    "The MMA generally precludes multiple 30-month stays for those applications to which it applies."  That is a statement from the FDA in a draft guidance document entitled "Listed Drugs, 30-Month Stays, and Approval of ANDAs and 505(b)(2) Applications Under Hatch-Waxman, as Amended by the Medicare Prescription Drug, Improvement and Modernization Act of 2003," published in October 2004.  But in the same document, FDA also stated, "Multiple 30-month stays, however, still may be possible in certain cases."  This is one such case.

    In 2008, Minrad, Inc. (now Piramal Critical Care, Inc.) filed an ANDA for a generic version of Suprane (desfluorane, USP) and submitted a paragraph IV certification to Baxter Healthcare's U.S. Patent No. 5,617,906.  Minrad sent a paragraph IV notice letter to Baxter, which Baxter received on December 12, 2008.  Within 45 days, Baxter filed suit against Minrad for infringement of the '906 patent, triggering a 30-month stay that expired on June 12, 2011.

    On June 7, 2011, just days before the 30-month stay expired, FDA granted Baxter's citizen petition requesting that FDA confirm that Baxter is entitled to a second 30-month stay.  The FDA's petition response explains:

    On June 23, 2009, Minrad changed the container closure system for its drug product and submitted an amendment to ANDA 90-363 to include the new closure system.  Once Minrad submitted the second paragraph IV certification to the '906 patent in connection with the revised product and sent notice to Baxter, and Baxter subsequently sued Minrad within 45 days of receiving that notice, the statutory requirements for a 30-month stay with respect to this paragraph IV certification were met.

    The FDA's response continues:

    The statute is unambiguous.  When a paragraph IV certification has been made to a patent for which information was submitted to FDA before the ANDA was submitted, and an action is brought for infringement of the patent that is the subject of the certification, a 30-month stay dating from receipt of the notice applies (section 505(j)(5)(B)(iii) of the Act).  Even if the statute were ambiguous, we would interpret it, consistent with its intent to provide an opportunity to litigate questions concerning patent infringement, to begin a 30-month stay when as here, an ANDA is amended to include a new certification reflecting a change in the product covered by the ANDA.

    As a result, FDA granted Baxter second 30-month stay, which will not expire until January 7, 2012.

    The lesson for generic drug companies:  if possible, do not change your drug product during the approval process.  If you do change your product, try to avoid having to send another paragraph IV notice letter.  On the flip side, the lesson for brand-name drug companies:  if you receive another paragraph IV notice letter from a company you've already sued, file another complaint against that company.  You may earn an additional 30-month stay.

    Hat tip to Steve Auten's Hatch-Waxman ANDA Litigation Forum on LinkedIn.

    POSTSCRIPT:  The '906 patent claims an "anaesthetic agent container for supplying a liquid anaesthetic" comprising certain physical features.  None of the claims recites desflurane–or any other pharmaceutical.  Thus, Minrad may have a viable argument that the '906 patent is improperly listed in the Orange Book.  It appears from Minrad's Answer, however, that Minrad has not sought the delisting of the '906 patent.

  • U.S. Supreme Court Confronts Inducement of Infringement Under Section 271(b) for the First Time–What Does it Mean for ANDA Litigation?

    Global-Tech Appliances v. SEB, No. 10-6 (U.S. 2011)

        by Aaron F. Barkoff

    Method-of-use patents are frequently asserted in ANDA litigation.  When they are, the patent owner alleges that if the ANDA is approved, the ANDA applicant would induce infringement under 35 U.S.C. §  271(b).  Section 271(b) states:  "Whoever actively induces infringement of a patent shall be liable as an infringer."

    Proving inducement of infringement in an ANDA case is often difficult for innovator pharmaceutical companies.  Under the Federal Circuit's 2006 en banc holding in DSU Medical v. JMS, proof of inducement "requires evidence of culpable conduct, directed to encouraging another's infringement."  Such evidence may be found in the ANDA applicant's proposed labeling, which might instruct physicians that the drug is indicated for a particular (patented) use.  But when an ANDA includes a "skinny" label and a section viii statement, the proposed labeling might not be useful evidence.  When the Supreme Court agreed to hear Global-Tech Appliances v. SEB, in which the Court would construe § 271(b) for the first time, some innovator companies were hopeful that the Court would effectively overrule DSU Medical and make it easier to prove inducement of infringement.

    The issue in Global-Tech, as stated by the Court, was "whether a party who 'actively induces infringement of a patent' under 35 U.S.C. § 271(b) must know that the induced acts constitute infringement."  In the case, SEB held a patent on a deep fryer.  Global-Tech sold infringing deep fryers to Sunbeam, Fingerhut and Montgomery Ward, each of which resold them in the United States under their own trademarks.  SEB alleged that Global-Tech violated § 271(b) by actively inducing Sunbeam, Fingerhut and Montgomery Ward to sell or offer to sell Global-Tech's deep fryers in violation of SEB's patent.  Global-Tech argued that inducement of infringement under § 271(b) requires knowledge of the patent, and since Global-Tech did not actually know of SEB's patent, it was not liable for inducement under § 271(b).

    Global-Tech's arguments failed in the district court, and last year the Federal Circuit affirmed.  The Federal Circuit held that actual knowledge of the patent is not required to support a finding of induced infringement–it was enough that Global-Tech "deliberately disregarded a known risk" that it would induce infringement.  Last week, in an 8-1 decision, the Supreme Court affirmed the Federal Circuit.  The Supreme Court tweaked the test, though, holding that "induced infringement under § 271(b) requires knowledge that the induced acts constitute patent infringement," and that such knowledge may be proven through the doctrine of "willful blindness."

    Innovator pharmaceutical companies might argue that, by requiring only "knowledge that the induced acts constitute patent infringement," the Supreme Court has established the test for proving inducement of infringement under § 271(b) and effectively overruled the Federal Circuit's test enunciated in DSU Medical.  And to an innovator company, it is relatively easy to prove that an ANDA applicant knows that doctors will prescribe its ANDA product for all of the uses for which the brand drug is approved, even if the ANDA product label omits one or more of those uses–considerably easier than producing "evidence of culpable conduct, directed to encouraging another's infringement" under DSU.

    In response, generic pharmaceutical companies might argue that the Supreme Court addressed an entirely different question in Global-Tech than the Federal Circuit addressed in DSU Medical, and thus DSU Medical is still controlling law.  In support, they might cite the following portion of the Court's opinion:  "[Global-Tech argues] that § 271(b) demands more than willful blindness with respect to the induced acts that constitute infringement.  This question, however, is not at issue here."  Indeed, the Federal Circuit's en banc holding in DSU Medical was based on the Supreme Court's holding in MGM v. Grokster, and the Court gave no indication in Global-Tech that it was reconsidering Grokster.

    Furthermore, the patent-in-suit in Global-Tech was directed toward an apparatus, not a method of use.  Therefore, every sale of the apparatus was an infringing sale; there were no non-infringing uses, as there might be in an ANDA case involving a section viii statement.  And the actual question addressed in Global-Tech–whether knowledge of the patent is required–is rarely an issue in ANDA litigation, because the patents are listed in the Orange Book.

    In the end, Global-Tech might have very little impact on ANDA litigation.  Time, and the lower courts, will tell.

    RELATED READING:

  • Obama Administration Urges Supreme Court to Grant Certiorari in Case on Orange Book Patent Use Codes

    Caraco Pharm. Labs. v. Novo Nordisk, No. 10-844 (U.S. 2011)

    Last week, in response to the Supreme Court’s request for its views, the Solicitor General’s office filed an amicus brief in Caraco v. Novo Nordisk and urged the Court to take the case.  At issue is the “patent delisting counterclaim” provision of the 2003 Medicare Modernization Act.  The case is an appeal from a Federal Circuit decision last year holding that the provision is not available to compel a change to a patent use code in the Orange Book.

    Patent use codes relate specifically to method-of-use patents.  FDA regulations require an NDA holder submitting a method-of-use patent for Orange Book listing to also submit a patent use code for the patent.  The purpose of the use code is to indicate “the approved indications or other conditions of use covered by [the] patent.”  21 C.F.R. 314.53(e).

    When a company files an ANDA with a section viii statement, asserting that it does not seek approval of its drug for a patented use, FDA compares the ANDA applicant’s proposed drug labeling to the patent use code to determine whether the section viii statement is acceptable.  If there is any overlap between the proposed labeling and the use code, FDA will reject the section viii statement and require the ANDA applicant to file a Paragraph IV certification instead.

    In this case, Novo’s U.S. Patent No. 6,677,358 claimed a method for treating diabetes comprising administering repaglinide in combination with metformin and its use code for the ‘358 patent was “a method for improving glycemic control in adults with type 2 diabetes mellitus.”  Caraco filed an ANDA for a generic version of PRANDIN (repaglinide) and included a section viii statement, asserting that it sought approval for repaglinide used alone—not in combination with metformin.  In other words, Caraco sought to “carve out” the patented use from its labeling, thereby trying to avoid inducing infringement of the ‘358 patent.

    Because Caraco’s proposed use overlapped with Novo’s use code, however, FDA rejected Caraco’s section viii statement, rejected Caraco’s carve-out labeling, required Caraco to file a Paragraph IV certification, and required Caraco to copy Novo’s PRANDIN labeling.  It did not matter that Caraco’s proposed use did not overlap with Novo’s patent claim—the FDA only checks the use code.  In the Paragraph IV litigation, Caraco filed a counterclaim seeking to compel Novo to revise the use code for the ‘358 patent to more narrowly tailor the use code to the method claimed in the ‘358 patent: administering repaglinide in combination with metformin.  The district court sided with Caraco and ordered Novo to change the use code, but the Federal Circuit reversed.  Caraco then appealed to the Supreme Court.

    The Federal Circuit’s decision has caused a great deal of concern to the generic drug industry, as seen in the five amicus briefs filed in support of Caraco’s cert petition (and none opposed).  Briefs in support were filed by Apotex; the Consumer Federation of America and U.S. PIRG; the Generic Pharmaceutical Association (GPhA); Mylan; and Teva.  In March, the Supreme Court asked the Solicitor General’s office for its views on the case, which many in the generic pharmaceutical industry took as a positive sign.  After the Solicitor General filed its brief last week, urging the Court to grant certiorari, the generic industry was even more encouraged, as reflected in GPhA’s press release.

    According to the Solicitor General:

    Under the Federal Circuit's decision, a brand-name manufacturer can effectively preclude generic competition by submitting an overbroad description of its method-of-use patent to FDA.  Congress enacted the counterclaim provision at issue here to combat precisely that sort of manipulation.  The court's ruling significantly impairs ANDA applicants' ability to secure FDA approval for their products, and hence deprives consumers the full benefit of generic competition.

    Despite the complex regulatory background and policy arguments, this case presents a relatively straightforward question of statutory interpretation: does the term "patent information" in the counterclaim provision encompass patent use codes or not?  By the end of June, the Supreme Court will announce whether it has decided to take up the case.

    RELATED READING:

  • AIPLA Chemical Patent Practice Road Show: Prosecution and Litigation Strategies, Chicago, June 23

    The AIPLA will be holding a full-day seminar entitled "Chemical Patent Practice Road Show: Prosecution and Litigation Strategies," on June 23rd at the Chicago Marriott Downtown.  AIPLA describes the seminar as "covering advanced issues relating to chemical patent prosecution and litigation.  The seminar features speakers from the USPTO, chemical and pharmaceutical companies, and nationally-known private practitioners."

    The agenda includes the following presentations:

    • Strategies for Drafting Chemical Patent Applications in the Pharmaceutical Arts
    • Freedom-to-Operate Strategies and Pitfalls in the Chemical Arts
    • A View from the Board of Current Issues Relating to Reexamination, by Michael Tierney of the USPTO
    • Prosecution Strategies to Overcome Inherency Problems
    • A National IP Strategy: An Idea Whose Time Has Come
    • Panel Discussion: Important Post-KSR Case Law that Chemical Prosecutors Need to Know, with Bradley Crawford, Troy Groetken and Alan Zombeck
    • Unique Perspectives on Litigating Chemical Patents and Litigation Tips for Drafting Chemical Applications
    • Sorting Out the Inducement Standard

    For more information or to register, please click here.

  • En Banc Federal Circuit Reins In Inequitable Conduct

    Therasense, Inc. v. Becton, Dickinson & Co. (Fed. Cir. 2011) (en banc)

        by Nabeela Rasheed

    In a landmark en banc decision today, the Federal Circuit rewrote the law of inequitable conduct.  This case was of great interest to the patent community, as evidenced by the 33 amicus briefs submitted.  From the pharmaceutical industry, amicus briefs were filed by Apotex; Sanofi-Aventis; Eli Lilly & Co.; BIO; Eisai; Johnson & Johnson; PhRMA; Teva; and GPhA.  In the decision, the Federal Circuit unabashedly states that it is reining in inequitable conduct because to do so is in the interests of patent prosecutors, inventors, courts and the public at large.

    The patent-in-suit, U.S. Patent No. 5,820,551, claims disposable blood glucose test strips for diabetes management.  The strips comprise an electrode configured to be exposed directly to whole blood–i.e., without a membrane covering the electrode.  The patent application was filed by Abbott in 1984 and underwent a protracted prosecution over a period of 13 years.  A key reference cited by the PTO for anticipation and/or obviousness was another Abbott patent (the '382 patent).

    During prosecution, the prosecuting patent attorney and the Director of R&D both made contributions in order to overcome the art-based rejections.  The attorney argued that the '382 patent required a membrane and the claims under examination did not.  But the PTO was unconvinced.  Thus, the Director of R&D submitted an affidavit analyzing the '382 patent and the patent attorney represented that the affidavit showed that the art cited required a membrane barrier for whole blood.  Meanwhile, several years earlier in the European counterpart application, Abbott did not categorically deny that there was a membrane in the '382 prior art device, but instead characterized it as serving a different purpose.  So in essence there was a discrepancy in how the patentee had characterized the prior art in two different jurisdictions–the EPO and the USPTO.

    At the district court, the ‘551 patent was held unenforceable for inequitable conduct because Abbott did not disclose to the PTO the statements made in the prosecution of the European patent.  There were also findings of invalidity and non-infringement.  Abbott appealed the judgments of invalidity, unenforceability and noninfringement.  Last fall, the Federal Circuit upheld noninfringement and invalidity.  Abbott then petitioned for rehearing en banc.

    In granting Abbott’s petition, the Federal Circuit “recognize[ed] the problems created by the expansion and overuse of the inequitable conduct doctrine.”  In today’s decision, the court reviewed the “unclean hands” line of cases that initially spawned the inequitable conduct doctrine (Keystone, Hazel-Atlas and Precision).  While the unclean hands doctrine remains for egregious acts of deliberate fraud, the inequitable conduct doctrine developed further to require a two-part test of intent and materiality, where the two tests were on a sliding scale.  That is, a showing that withheld prior art was especially material would compensate if there were little evidence of bad intent.  In today's decision, the court does away with this sliding scale, noting that that it “conflate[s] and dilute[s]” both the standard of materiality and intent.

    (more…)

  • District Court Grants TRO Against Mylan’s Generic Amrix–After Finding Patents Invalid

    In Re: Cyclobenzaprine Hyldrochloride Extended-Release Capsule Patent Litigation, No. 09-md-2118-SLR (D. Del. 2011)

    In a strange turn of events, the district court that just eight days earlier found the asserted claims of the patents on Amrix invalid, granted a motion for a temporary restraining order against Mylan.

    As we previously reported, on May 12, following a seven-day bench trial conducted last September and October, the U.S. District Court for the District of Delaware held that the asserted claims of U.S. Patent Nos. 7,387,793 and 7,544,372 are invalid due to obviousness.  This decision cleared the way for Mylan, the first paragraph IV filer, to launch its generic version of Amrix.  As we reported, Mylan did so on May 13, triggering its 180-day exclusivity period.

    Notwithstanding that they lost after trial, on May 15 the plaintiffs filed a motion for a temporary restraining order.  This was followed by three rounds of briefs by each side–including briefs filed each day last week–until the district court granted the motion last Friday.

    Given that one of the legal requirements for granting a TRO is a "likelihood of success on the merits," and the district court previously found after a full trial that the plaintiffs lost on the merits, it is very surprising that the court granted the TRO.  Did the court, after reconsideration, find that its decision was wrong on the merits?  No–in its Memorandum Order, the court defended each of the findings that plaintiffs asserted to be erroneous.  But inexplicably, the court concluded that "plaintiffs' success on appeal is just as likely as not," and therefore "this factor marginally supports a temporary restraining order."

    Later on Friday, Mylan filed an Emergency Motion for Reconsideration, stating that the court "committed fundamental, material errors of law."  Specifically, according to Mylan, the court "did not find that Plaintiffs were likely to succeed on the merits but rather that 'plaintiffs' success on appeal is just as likely as not.'  As a matter of law, this sort of 50-50 assessment is insufficient to establish a likelihood of success and destroys the basis for the TRO."  Mylan, of course, is concerned that its 180-day exclusivity period will tick away while it's prevented from marketing.

    While the court granted the plaintiffs' motion, it has not yet entered an order enjoining Mylan.  The court has scheduled a hearing for tomorrow at 9:00 am, and presumably will hear argument on Mylan's emergency motion.

    UPDATES:

    • On May 24, Mylan filed a supplemental brief in support of its Emergency Motion for Reconsideration
    • Later on May 24, in this Order, the district court denied Mylan's Emergency Motion for Reconsideration
    • Also on May 24, in this Order, the district court entered an injunction against Mylan
    • Still later on May 24, Mylan filed a Notice of Appeal to the Federal Circuit
    • On May 25, in this Order, the Federal Circuit stayed the district court's May 24 injunction

  • ACI “Biosimilars” Conference, New York City, June 7-8

    American Conference Institute is holding their 2nd annual "Biosimilars" conference in New York City on July 7th and 8th, at the Millenium UN Plaza Hotel.  According to ACI, this is "the definitive forum on the legal, regulatory, and commercial realities of generic biologics."

    The agenda includes the following presentations:

    • Update on current FDA position and initiatives regarding biosimilars
    • Predicting, preparing and positioning for the FDA's implementation of the biosimilar pathway
    • Scrutinizing the costs and complexities behind biosimilar research and development
    • Debating the practical implications of a 12-year exclusivity period: Striking a balance between innovator and biosimilar interests
    • No two biologics are alike: Defining biosimilarity and meeting the heightened standard of interchangeability under the statute
    • Branding and promotional considerations for biosimilars
    • Learning from the global development of biosimilars: Enforcement and risk management strategies to protect your biologic on the international stage
    • An overview of the statutory dispute resolution mechanisms: Steering clear of any potential gaps in the litigation
    • Developing proactive procedures and strategies today for the flood of biosimilar litigation tomorrow: From early planning through the exchange of patent lists
    • Developing proactive procedures and strategies today for the flood of biosimilar litigation tomorrow: From the exchange of patents to be litigated to product launch
    • Ascertaining the type and volume of clinical data necessary to establish biosimilarity
    • Structuring a patent portfolio strategy to protect IP in light of FOB legislation
    • Alternative routes to market for biosimilars: Evaluating the benefits of using the abbreviated pathway

    In addition, there is a pre-conference science primer, "Biologics Science 101: Understanding and Deconstructing the Complicated Scientific Principles Behind Biosimilars," on June 6th; and a post-conference master class, "In-Depth Breakdown of the Biosimilar Framework in the EU," on June 9th.

    Orange Book Blog readers can receive a $200 discount by using code OBB 200.  For more information or to register, please visit the conference website.

  • Mylan Launches Generic Amrix; Cephalon Files Motion for TRO

    In Re: Cyclobenzaprine Hyldrochloride Extended-Release Capsule Patent Litigation, No. 09-md-2118-SLR

    Last Thursday, the U.S. District Court for the District of Delaware invalidated the asserted claims of two patents protecting Amrix (cyclobenzaprine), clearing the way for Mylan to launch its generic version (albeit at-risk).  On Friday, Mylan announced that it did just that, with 180-day exclusivity.

    Today, Cephalon filed a Motion for a Temporary Restraining Order in the district court, aiming to enjoin Mylan's sales of generic Amrix.  Unfortunately, Cephalon's brief and supporting declarations were filed under seal, and are therefore not publicly available.  Cephalon presumably is asking the district court to halt Mylan's sales while it seeks an emergency stay of the district court decision in the Federal Circuit.

    A TRO, however, is an extraordinary remedy.  And given that the district court did not seem to have any doubt of the invalidity of the asserted claims, it would be surprising if the TRO were granted.

    UPDATE:  On May 16, Watson Pharmaceuticals announced that it launched an authorized generic version of Amrix, supplied by Cephalon's Anesta AG subsidiary.

  • ACI “Life Sciences Collaborative Agreements and Acquisitions” Conference, San Francisco, July 20-21

    American Conference Institute is holding its "15th Advanced Forum on Life Sciences Collaborative Agreements and Acquisitions" in San Francisco, California on July 20th and 21st.  According to ACI, this conference provides an opportunity to "meet the key dealmakers who will give you the contacts and intelligence you need to launch your company and product portfolio to the next level."

    The agenda includes:

    • Market watch: Understanding the driving forces and changing dynamics impacting the current deal-making landscape
    • Integrating increasing M&A activity into your business development strategy
    • Best practices for selecting the deal structure and negotiating your most beneficial collaborative agreements yet
    • Negotiating options, staged acquisitions, hybrid transactions and straight-forward M&As
    • Streamlining entry into lucrative emerging markets via strategic partnering
    • Beyond the shadow of the valley: Alternative pathways and partnerships to facilitate funding drug discovery and development
    • Preparing for the exit: Proactively drafting critical termination provisions to protect company assets
    • Protecting current and future collaborations: The dos and dont's of partnering/negotiations
    • Aligning divergent interests to negotiate mutually beneficial collaborative research agreements with academic institutions
    • Utilizing applicable valuation models to set realistic expectations for a deal
    • Mitigating legal risks in the life sciences M&A setting: a six-step approach
    • Licensing strategies for biosimilars: Regulatory, commercial and IP considerations for the new frontier

    In addition, there is a post-conference master class, "Conducting Effective & Strategic Due Diligence for Life Sciences Partnering and M&A," on July 22nd.

    Orange Book Blog readers can receive a $200 discount by using code OBB 200.  For more information or to register, please visit the conference website.

     

  • ACI “Hatch-Waxman Boot Camp” Conference, San Diego, July 18-19

    American Conference Institute is holding a "Hatch-Waxman Boot Camp" conference in San Diego, California on July 18th and 19th, at the Hilton San Diego Resort & Spa.  ACI calls this conference "a primer on IP basics and regulatory fundamentals relative to small molecules and biologics."

    Here's the agenda:

    • Key agencies overview: Understanding the jurisdiction and interplay of the FDA and PTO in the patenting of drugs and biologics
    • Identifying and comprehending pre-commercialization concerns relative to small molecules and biologics
    • Exploring the link between the FDA approval process and the patenting of drugs and biologics
    • IP overview for drugs and biologics: Hatch-Waxman, BPCIA, trade dress, and more
    • Paragraph IV disputes and litigation
    • How the dynamics of biosimilars and changing the Hatch-Waxman landscape
    • Orange book listings, de-listings and related challenges
    • Bioequivalence and the "same active ingredient" vis-a-vis patentability
    • An in-depth look at 180-day exclusivity
    • Comprehending the intracacies of non-patent/regulatory exclusivity
    • Assessing patent protections afforded under the 271(e)(1) safe harbor
    • Examining pharmaceutical patent extensions: Patent term adjustment and patent term extension

    In addition, there is a post-conference Interactive Biosimilars Strategy Session on July 20th.

    Orange Book Blog readers can receive a $200 discount by using code OBB 200.  For more information or to register, please visit the conference website.