Orange Book Blog

At the intersection of Patent and FDA Law

Recent Posts

  • Mylan Launches Generic Norvasc; Other Generics to Follow Soon?

    Mylan announced in a press release today that it has launched its generic Norvasc (amlodipine besylate).  Mylan’s generic launch follows the Federal Circuit’s decision yesterday, invalidating Pfizer’s patent on Norvasc.  The case presents some very interesting issues involving the interaction between patent rights, pediatric exclusivity, and 180-day exclusivity.

    Last month, Mylan lost its patent challenge when Judge Terrence F. McVerry of the U.S. District Court for the Western District of Pennsylvania found that Pfizer’s patent is valid, enforceable and infringed by Mylan.  At the time, the district court enjoined Mylan from marketing its generic Norvasc "until after the expiration of Pfizer’s ‘303 patent term, as extended by the pediatric exclusivity period."  Pfizer’s patent expires this Sunday, March 25; Pfizer’s pediatric exclusivity expires six months later, on September 25.  Since then, Pfizer and Mylan have been busy filing motions to amend the district court’s injunction and Mylan has appealed the decision to the Federal Circuit.

    On March 8, Pfizer asked the district court to modify its injunction to include a "section 271(e)(4)(A) order" stating that the effective date of approval of Mylan’s ANDA shall not be earlier "than the date of expiration of the ‘303 patent (March 25, 2007, with attached six months of pediatric exclusivity ending on September 25, 2007, to which Pfizer is entitled)."  The FDA had already granted final approval to Mylan’s ANDA and, according to Pfizer, "in a telephone conversation on March 7, 2007, the FDA advised Pfizer that the FDA will not reset Mylan’s effective approval date without a judgment including a section 271(e)(4)(A) order."

    Mylan opposed Pfizer’s motion and filed its own motion to amend the district court’s order, asking the district court to enjoin Mylan only until Pfizer’s patent expires on March 25.  According to Mylan’s motion:

    Pediatric exclusivity does not grant a drug maker a six month patent extension, but acts [only] to prohibit FDA from granting final approval.  Here Mylan has already received final approval and is the only ANDA filer with final approval.  In effect, then, the pediatric exclusivity period applies to all generic competitors except Mylan, thus giving Mylan a six-month head start over generic competitors.

    In response, Pfizer filed a combined opposition and reply.  Pfizer argued that its proposed amended judgment was "purely formal, incorporating the precise words of the statue.  Mylan’s proposed amended judgment, on the other hand, seeks to . . . deny Pfizer its right of pediatric exclusivity without any basis whatsoever."

    On March 16, the district court reached a sort of compromise, ordering that Mylan’s ANDA shall not be approved until Pfizer’s patent expires and enjoining Mylan until then.  Mylan then filed an emergency motion to stay the court’s new order, arguing that "there is a real danger that the Court’s order will prompt the FDA to revoke [Mylan’s] approval, keeping Mylan off the market even after the patent has expired."  Mylan worried that it would lose its 180-day exclusivity rights if the FDA revoked its approval.  Three days later, Pfizer opposed the motion.  Later that same day, the court denied it.

    Yesterday, of course, the big news hit: the Federal Circuit invalidated Pfizer’s patent in a separate case against Apotex, who had filed its own ANDA to market generic Norvasc (albeit later than Mylan).  Mylan’s lawyers immediately picked up the phone, called Judge McVerry, and made "an emergency oral telephonic motion for a stay of the injunctive relief."  Recognizing that Mylan’s lawyers presented the same emergency motion to the Federal Circuit, Judge McVerry denied Mylan’s motion.

    At the same time, Mylan filed this complaint against the FDA today in the District of Columbia district court, asking the court to enjoin FDA from taking any action that would "disturb the final approval granted to Mylan’s ANDA."  Mylan indicated that in a phone call with Mylan’s counsel, "FDA counsel stated that FDA would revoke Mylan’s final approval and convert it to a tentative approval," if the Federal Circuit did not stay the March 16 order "by mid-day on March 23, 2007."  Mylan also filed this emergency TRO motion.

    Apparently the Federal Circuit granted Mylan’s motion for a stay of the March 16 order–otherwise Mylan could not have launched its generic Norvasc.  The Federal Circuit’s action seems to moot the lawsuit Mylan filed today in the D.C. district court.

    Now that Mylan has launched, the interesting question is whether the FDA will approve any other generics when Pfizer’s patent expires on Sunday.  In its press release today, Mylan states that its generic launch triggered its 180-day exclusivity period, precluding the FDA from approving any other generics.  This AP story published today, however, suggests that Apotex has a different understanding, and expects to launch its own generic Norvasc "in the very near future."

    Meanwhile, Pfizer announced late today that in response to Mylan’s generic launch, it has launched an authorized generic Norvasc through its Greenstone subsidiary.  Pfizer added that it "will continue to pursue all available legal remedies to protect the market for Norvasc through a six-month pediatric exclusivity period that expires in September, 2007."

    Stay tuned . . . this story is developing quickly.

    RELATED READING:

    UPDATES:

    • Mylan brief in support of its motion for a stay, pending appeal, of the district court’s March 16 Order
    • Pfizer brief in support of its motion to lift the Federal Circuit’s temporary stay of the March 16 Order
    • Fed. Cir. March 26 Order granting Mylan’s motion and denying Pfizer’s

  • Federal Circuit Invalidates Pfizer’s Norvasc Patent; Mylan’s Generic Expected to Launch Soon

    Pfizer v. Apotex, No. 2006-1261 (Fed. Cir. 2007)

    The U.S. Court of Appeals for the Federal Circuit invalidated Pfizer's patent on Norvasc today, clearing a major hurdle for Mylan in its bid to launch a generic version of Norvasc.  The FDA has already granted final approval to Mylan's ANDA for generic Norvasc and Mylan, as the first ANDA filer, holds the 180-day exclusivity rights.  Norvasc (amlodipine besylate) is Pfizer's blockbuster treatment for high blood pressure, with annual U.S. sales of $2.5 billion.

    Three different U.S. district courts had previously upheld the validity of Pfizer's Norvasc patent (U.S. Patent No. 4,879,303), making today's appeals court decision somewhat of a surprise.  In January 2006, the Northern District of Illinois upheld the patent in Pfizer's case against Apotex; in August 2006, the Middle District of North Carolina upheld the patent in Pfizer's case against Synthon; and last month, the Western District of Pennsylvania upheld the patent in Pfizer's case against Mylan.  All three district court decisions were appealed.  Today's Federal Circuit decision came in the case against Apotex, though the invalidity ruling affects all three cases.

    In the Federal Circuit opinion released today, a unanimous three-judge panel determined that claims 1-3 of the '353 patent, directed to amlodipine besylate and pharmaceutical and tablet formulations thereof, are invalid as obvious.  More specifically, the court concluded that amlodipine besylate would have been obvious in light of Pfizer's own U.S. Patent No. 4,572,909, which discloses amlodipine and related compounds, together with various articles describing besylate salts of different compounds.

    Generic Norvasc was not expected to hit the market until September, when Pfizer's pediatric exclusivity expires.  Now, some analysts are predicting that Mylan will launch its generic Norvasc as early as next week.  If that happens, Mylan should probably send a thank you card to Apotex for achieving the invalidity decision in the Federal Circuit.

    Before Mylan can launch its generic Norvasc, however, a court will need to lift the injunction that was entered when Pfizer defeated Mylan in the district court last month.  Pfizer, for its part, announced in a press release today that it is considering all options, including filing a request with the Federal Circuit for reconsideration of today's decision.

    RELATED READING:

  • Pfizer Defeats Teva in Celebrex Case

    Pfizer et al. v. Teva Pharms. USA, No. 04-754 (D.N.J. 2007)

    In a 201-page opinion released today, Judge John C. Lifland of the U.S. District Court for the District of New Jersey found all three of Pfizer's patents on Celebrex (celecoxib) valid, enforceable, and infringed by Teva, who had sought to market a generic version of Celebrex before the patents expire in 2015.  Celebrex is Pfizer's blockbuster treatment for arthritis.

    The patents in suit are U.S. Patent Nos. 5,466,823, 5,563,165, and 5,760,068.  They cover celecoxib (the active ingredient in Celebrex), a broad genus of compounds that includes celecoxib, pharmaceutical compositions including the compounds, and methods of using the compounds.  Teva challenged the validity of the patents on grounds of obviousness, best mode, and obviousness-type double patenting, and the enforceability of the patents on grounds of inequitable conduct.  Teva will likely appeal the decision to the Federal Circuit Court of Appeals.

    RELATED READING:

  • News From PhRMA Annual Meeting

    PhRMA held its annual meeting today and yesterday in Washington.  So far, there seems to be relatively little news coming out of the meeting–at least compared to GPhA’s annual meeting earlier this month.  Links to a few stories are provided below; I’ll add more as I find them:

    Incidentally, the Business and Media Institute recently sent me this report on media bias against the pharmaceutical industry.

  • Decision on Tamoxifen Cert Petition Expected Soon

    According to this article in today’s Legal Times, the Supreme Court may decide as early as next Monday whether or not to grant certiorari in In Re: Tamoxifen Citrate Antitrust Litigation, the latest "reverse payment" settlement case to be presented to the Court.

    In the case, patients, health insurance companies, and consumer advocacy groups are challenging the legality of a patent litigation settlement that included a $21 million payment from AstraZeneca to Barr Labs and an agreement by Barr to delay marketing its generic tamoxifen product until Astra’s patent expired.  Tamoxifen, a treatment for breast cancer, is the most widely prescribed cancer drug in the world.

    Last year, the Court denied certiorari in a similar case, FTC v. Schering.  There, the Court asked for the views of the Solicitor General, who recommended denying cert.  At the time, the Solicitor General suggested that the Tamoxifen case might present a better vehicle for addressing the issue of reverse payment settlements.  The Court has not yet asked the Solicitor General to submit an amicus brief in Tamoxifen, but that remains a possibility.

    Links to the petition stage briefs are provided below.  Thanks very much to everyone who sent me copies of the briefs.

    BRIEFS:

    RELATED READING:

    UPDATES:

    • On March 18, the Supreme Court asked the Solicitor General to file an amicus brief setting forth the Government’s position on the case.  Thus, the Court may not decide until Fall whether or not to take this case.  Patently-O has more.

  • ACI “3rd Annual In-House Counsel Forum on Pharmaceutical Antitrust,” May 15-16, New York City

    American Conference Institute has announced that it will hold the third installment of its “unique antitrust event, designed specifically for the entire pharmaceutical industry…brand names and generics alike," May 15-16, 2007, at the Warwick New York Hotel in New York City.

    The conference will feature addresses by FTC Chairman Deborah Platt Majoras, Assistant Attorney General Thomas O. Barnett, and nine other federal and state enforcement officials.  It will also feature faculty from Eli Lilly, Forest Laboratories, Mayne Pharma, Merck, Mylan, Pfizer, Purdue Pharma, Upsher-Smith, and Wyeth.

    The following timely topics will be addressed:

    • Overcoming the uncertainty that exists with patent settlements and reverse payments
    • Examining the role of authorized generics in the market and impact of the FTC study
    • Exploring new antitrust concerns with exclusive dealing, tying, and bundling
    • Addressing the implications of the FTC Staff Report on the Noerr-Pennington doctrine
    • Determining whether product improvements are exclusionary
    • Avoiding antitrust dilemmas in mergers and acquisitions
    • Drafting and executing licenses that pass antitrust law scrutiny 

    The co-chairs for the conference are Thomas Leary of Hogan & Hartson and Seth Silber of Wilson Sonsini Goodrich & Rosati.  Additional details, as well as registration information, are available at the conference website.

    ACI is offering Orange Book Blog readers a $200 discount for the conference.  When registering, use discount code 710OBB.

    Orange Book Blog is a media partner of this conference.

  • “FDA Law Blog” Goes Live

    Jeffrey Wasserstein and Kurt Karst of Hyman, Phelps & McNamara, PC, recently launched FDA Law Blog, a new site promising to provide timely updates on FDA enforcement actions, proposed rules, and important topics in food and drug law.  Already, FDA Law Blog is reporting on recent FDA warning letters, draft guidance, and ANDA suitability petitions.

    Kurt Karst has been an invaluable contributor to Orange Book Blog ever since we started the blog last May, sending us new court decisions and serving as a great resource.  We look forward to reading FDA Law Blog and continuing to collaborate.  Good luck, Kurt and Jeff!

  • Pharma News Briefs

    • Bloomberg reports that the topic of reverse payment settlements of Hatch-Waxman litigation came up in a recent Senate hearing.
    • Bloomberg TV interviewed me yesterday about reverse payment settlements.  On Pharma has the video.
    • DUSA Pharmaceuticals announced that a federal court recently lifted the preliminary injunction that prevented River’s Edge Pharmaceuticals from selling generic Nicomide, a treatment for acne.
    • Pharmalot has this post on the most recent IMS numbers, which indicate that U.S. prescription drug sales rose 8% last year to $275 billion.

  • Senate Committee on Health Hears Testimony on Follow-on Biologics

    The U.S. Senate Committee on Health, Education, Labor, & Pensions held a hearing this morning on follow-on biologics.  A complete video recording is available on the hearing web-page.  The written testimony of each witness is available on the same page (click on the red icon appearing after each person’s name).

    In opening remarks, Sen. Kennedy (D-MA), the Chairman of the Committee, noted that he recently sat down with leaders of several biotechnology companies based in his home state of Massachusetts.  He expressed his belief that any regulatory scheme for follow-on biologics must be guided by three principles: (1) it must be led by the science; (2) protecting patients’ safety is essential; and (3) innovation must be valued and promoted.  Sen. Enzi (R-WY), the Republican leader on the Committee, echoed Sen. Kennedy’s remarks.  He emphasized, “we must not rush a solution through Congress,” or else “we risk endangering lives.”  Sen. Clinton (D-NY), a co-sponsor of the Access to Life-Saving Medicine Act, which would establish an abbreviated pathway for the approval of follow-on biologics, sensed that all sides acknowledge that science has advanced far enough to make follow-on biologics a reality.  She said, “we are debating how, not if, and it will be up to this committee when.”

    Sen. Schumer (D-NY), also a co-sponsor of the Access to Life-Saving Medicine Act, was the first witness to speak.  He began by announcing that “the science is there now.”  Sen. Schumer made a few points regarding the European Union’s framework for regulating follow-on biologics (or “biosimilars,” as they’re called in Europe).  He said the EU has a highly regulated system that’s “arguably burdensome.”  He noted that Europe has approved only two biosimilars in the four years since the EU’s regulatory framework has been in place.  With regard to patent rights, Sen. Schumer said that the Hatch-Waxman Act struck a balance, but in his view created an imbalance for biologics since biologics can receive five years of New Chemical Entity exclusivity and seven years of Orphan Drug Exclusivity, but are free of competition from generics.

    Following Sen. Schumer, the Committee heard from a panel of four experts:

    • Sid Banwart, VP of Human Services for Caterpillar, noted that prescription drugs account for 25% of Caterpillar’s health care spending for its 95,000 employees worldwide.  He expressed concern that biologic drugs are the “single fastest growing category of health costs” for Caterpillar, having increased 45% since 2004, and stated that “the trend is not sustainable.”
    • Dr. Jay Siegel, President of Biotechnology R&D at Johnson & Johnson and a 20-year veteran of FDA’s Center for Biologics Evaluation and Research, provided the innovator/biotechnology company perspective.  In his view, pre-marketing clinical trials of biologics in humans should always be required.  Moreover, Dr. Siegel believes follow-on biologics should not be substitutable with innovator biologics because the two can never be identical.  Of course, substitution at the pharmacy level is the holy grail for the generics industry, since that’s where the real money is.
    • Nicholas Rossignol, Administrator of the European Commission Pharmaceuticals Unit, spoke next.  He emphasized that there is a range of complexity in biologics (e.g., a vaccine is much more complex than a small protein such as insulin), which must be considered in any regulatory scheme.  He explained that substitutability is regulated at the individual country level in Europe, and some European nations have allowed substitution of certain follow-on biologics.
    • Finally, Dr. Ajaz Hussain spoke on behalf of Sandoz and provided the generic industry’s perspective.  Dr. Hussain expressed his belief that substitutability is an important public health goal and that follow-on biologics can be made to be substitutable.

    In the question and answer session that followed, all four panelists seemed to agree that the FDA currently has the expertise and is equipped to properly regulate follow-on biologics.  Moreover, the four panelists agreed that the primary goal is ensuring patient safety.  The panelists (and certain Senators on the Committee) disagreed about whether the Access to Life-Saving Medicine Act, as currently written, adequately protects patient safety.  Sen. Hatch (R-UT) stated clearly that he cannot support the current bill due to safety concerns.  Sen. Clinton hinted at possible amendments to the Act that might represent a compromise.

    RELATED READING:

  • Senate Committee on Health to Hold Hearing on Follow-on Biologics

    The U.S. Senate Committee on Health, Education, Labor, & Pensions, chaired by Sen. Edward M. Kennedy (D-MA), is planning to hold a full committee hearing on follow-on biologics this Thursday, March 8, at 10 a.m. eastern time.  Those expected to testify include Sen. Charles Schumer (D-NY), co-sponsor of the “Access to Life-Saving Medicine Act,” as well as pharmaceutical industry executives.  Live audio and video of the hearing will be available on this page of the committee’s website. 

    Last month, lawmakers in the House and Senate re-introduced legislation that would establish an abbreviated pathway for FDA approval of follow-on biologics (sometimes also referred to as “biogenerics”).  Since then, reports have indicated that the legislation may be attached to the Prescription Drug User Fee Act, which must be renewed before October 1 of this year.  Members of both parties have recently indicated that passage of follow-on biologics legislation is a top priority for the current Congress.

    Sales of biologic drugs reached $56 billion in 2005, accounting for 20% of total pharmaceutical sales.  Understandably, generic drug makers are anxious to enter this market.  In addition, with the annual cost of some biologic drugs surpassing $100,000, state Medicare programs and health insurance companies would like to see generic versions of biologic drugs made available as soon as possible.  On the other hand, biologics are far more complex than conventional (i.e., small molecule) drugs.  Accordingly, innovator drug companies want to ensure that appropriate safety and efficacy studies are conducted before any follow-on biologics are approved.

    RELATED READING:

    UPDATES: