Orange Book Blog

At the intersection of Patent and FDA Law

Recent Posts

  • Senate Judiciary Committee Plans Hearing on Reverse Payment Settlements of Hatch-Waxman Cases

    This Wednesday, January 17, at 10 am, the Senate Judiciary Committee will hold a hearing entitled "Paying Off Generics to Prevent Competition with Brand Name Drugs: Should it Be Prohibited?"  The hearing is intended to examine the effects of "reverse payment" settlements of Hatch-Waxman litigation, in which an innovator drug company makes a cash payment to a generic drug company, who in return agrees to delay the launch of its generic drug product.

    According to the Notice of Full Committee Hearing, those called to testify include:

    Mr. Leibowitz will testify first and will be followed by a panel that includes the other four speakers.  In the past, the FTC and consumer groups have vigorously opposed reverse payment settlements.  Meanwhile, both innovator and generic drug companies have supported allowing such settlements, arguing they resolve costly litigation on terms acceptable to both sides.  The testimony provided at Wednesday’s hearing is expected to be posted on the hearing webpage.

    The Senate Special Committee on Aging, chaired by Sen. Kohl (D-WI), held a similar hearing last year.  Also last year, Senators Kohl, Leahy (D-VT), Grassley (R-IA), and Schumer (D-NY) introduced a bill called the "Preserve Access to Affordable Generics Act," which would have banned reverse payment settlements.  Sen. Kohl recently re-introduced that bill and several other bills concerning pharmaceuticals in the new Congress.

  • Ethyol Case Between MedImmune and Sun Pharma Heats Up

    MedImmune Oncology v. Sun Pharm. Indus., No. 04-2612 (D. Md. 2007)

    MedImmune earns about $100 million annually from sales of Ethyol (amifostine), an injectable drug approved for the relief of certain side effects of chemotherapy and radiation therapy.  Sun Pharmaceutical Industries filed an ANDA to market a generic version of Ethyol.  In what appears to have become the standard strategy to protect sales of a brand name drug against generic competition, MedImmune responded by filing both a patent infringement lawsuit in court and a citizen petition with the FDA.

    Last week in its patent infringement suit, MedImmune lost one battle and won another.  Judge Marvin J. Garbis of the U.S. District Court for the District of Maryland granted Sun’s motion for summary judgment of noninfringement as to MedImmune’s U.S. Patent No. 5,424,471 and denied Sun’s motion for summary judgment of nonfringement as to the other patent in suit, U.S. Patent No. 5,591,731.  Click here for the memorandum opinion and order.

    MedImmune asserted the product-by-process claims of the ‘471 patent, arguing on the basis of the Federal Circuit’s decision in Scripps v. Genentech, 927 F.2d 1565 (Fed. Cir. 1991), that the claimed product is not limited by the process steps.  The court, however, thought the better rule was set forth in Atlantic Thermoplastics v. Faytex, 970 F.2d 834 (Fed. Cir. 1991), which held that process steps of product-by-process claims do impart limitations.  Because MedImmune and Sun did not dispute the fact that Sun makes its amifostine without using the process steps recited in the ‘471 patent, the court granted Sun’s motion for summary judgment of noninfringement.  (Interestingly, other district courts have opted to follow the Scripps rule.)

    The asserted claims of the ‘731 patent are product claims, directed to "thermally-stable, sterile, crystalline amifostine trihydrate."  However, the parties disputed whether the claimed crystalline amifostine must be "vacuum dried."  Because the court found that both sides presented reasonable arguments as to the putative inclusion of a "vacuum dried" limitation, the court denied Sun’s motion for summary judgment of noninfringment of the ‘731 patent.  The court has scheduled a Markman hearing for June 6, 2007, to make a final determination on claim construction.

    MedImmune filed its citizen petition relating to Ethyol on October 10, 2006, asking the FDA "to refuse to approve any ANDA for an amifostine product with labeling that omits dosage, administration, and other information related to the consequences of using the drug to reduce the incidence of xerostomia ["dry mouth"] in head and neck cancer patients being treated with radiotherapy."  MedImmune’s petition was clearly meant to block approval of Sun’s ANDA.

    Ethyol is approved for two indications: (1) the reduction of cumulative renal toxicity associated with the repeated administration of cisplatin in patients with advanced ovarian cancer; and (2) the reduction of moderate to severe xerostomia, or dry mouth, in patients undergoing post-operative radiation treatment for head and neck cancer.  According to MedImmune’s citizen petition, Sun Pharma "carved out" the second indication from the proposed labeling in its ANDA (presumably because MedImmune has method of treatment patents covering that use) and seeks approval for only the first indication.  MedImmune asserts in its citizen petition that only 2% of patients taking Ethyol take it for the first indication, which requires a dose three times as high as that for the second indication.  MedImmune claims "it would be unsafe to approve a generic version of Ethyol, yet allow the product to contain instructions on a dose that is simply incorrect for most patients for whom the drug is indicated."

    MedImmune filed the patent infringement suit in August, 2004, and therefore the 30-month stay on approval is set to expire next month.  It will be interesting to see whether the FDA decides MedImmune’s citizen petition before then.

    RELATED READING:

  • Biovail Continues to Fight FDA, Anchen, Impax, and Teva to Protect Wellbutrin XL

    Last August, the U.S. District Court for the Central District of California granted summary judgment of noninfringment to Anchen Pharmaceuticals in its case against Biovail over generic Wellbutrin XL.  Biovail has appealed to the Federal Circuit, but in the meantime, on December 15, 2006, the FDA granted final approval to Anchen's ANDA for Wellbutrin XL (bupropion HCl), 150 mg and 300 mg.  Having obtained final approval, Anchen could have launched at risk, but it chose not to.  Instead, Anchen selectively waived its 180-day exclusivity period for the 300 mg product in favor of Impax, who, in partnership with Teva (being deep-pocketed and less risk-averse) launched its own generic Wellbutrin XL, 300 mg.  Wellbutrin XL is an extended release version of Wellbutrin, the popular antidepressant manufactured by Biovail for GlaxoSmithKline, and had over $1 billion in sales last year.

    In response to the Impax approval and launch, on December 18, 2006, Biovail filed a complaint against the FDA in the U.S. District Court for the District of Maryland, asserting that it was entitled to a 30-month stay prior to FDA approval of Impax's ANDA.  At the same time, Biovail filed a motion for temporary relief.  The FDA opposed Biovail's motion, asserting that while Biovail timely filed an infringement action against Impax on Wellbutrin XL, 150 mg, Biovail failed to timely amend its complaint to include an infringement count with respect to the 300 mg dosage form.  Teva intevened, filing its own opposition brief.  On December 21, 2006, the court denied Biovail's motion, thereby allowing Teva/Impax to continue marketing its generic product.  Patent owners must file suit within 45 days of receiving notice of a paragraph IV certification, and it appears that Biovail's delay in this case may have been costly.

    Biovail also has a suit pending against the FDA in the U.S. District Court for the District of Columbia.  In that case, on December 18, 2006, Biovail filed a motion seeking to enjoin the FDA from approving any ANDAs for generic Wellbutrin XL and to stay the effectiveness of prior approvals, focusing its attention on the Anchen approval and the December 14, 2006, FDA denial of a Biovail citizen petition concerning Wellbutrin XL.  The FDA has filed an opposition to Biovail's motion, as have Anchen and Teva/Impax (as intervenors), and Biovail has filed a reply.  Biovail's arguments center on its assertion that the FDA wrongfully approved generic Wellbutrin XL with a label that falsely and misleadingly implies that the generic product was tested for risk of seizures, while the FDA and intervenors assert that Biovail's motion is an attempt to inappropriately extend its monopoly on Wellbutrin XL.  The court has not yet decided Biovail's motion.

    RELATED READING:

  • Abbott Labs Under Scrutiny for Alleged Antitrust Violations

    Abbott Laboratories is currently fighting antitrust allegations relating to two of its best-selling drugs: Norvir, a protease inhibitor used in AIDS treatment, and Hytrin, a drug used to treat enlarged prostate and hypertension.

    Last week the Wall Street Journal ran a cover story on the Norvir case entitled "Inside Abbott’s Tactics to Protect AIDS Drug."  According to the article, in December 2003 Abbott quintupled the price of Norvir in order to protect sales of Kaletra, its more profitable AIDS medication.  Other options that Abbott considered but ultimately rejected included withdrawing Norvir from the market entirely and selling Norvir only in a liquid formulation that one Abbott executive said tastes "like someone else’s vomit."  The article is based on previously undisclosed Abbott documents (available at WSJ.com with a subscription).  Abbott’s price hike has sparked an investigation by the Illinois Attorney General’s office, as well as federal antitrust lawsuits.

    At the same time, Abbott is fighting allegations of unlawful monopolization in connection with Hytrin.  Kaiser Foundation Health Plan, a health care provider, is the plaintiff in the case.  According to Kaiser’s appeal brief, filed with the 9th Circuit last November, "Abbott extended its Hytrin monopoly by seeking objectively invalid new patents and gaming the regulatory system to delay generic competition for four additional years."  In addition, Kaiser alleged that Abbott paid Geneva Pharmaceuticals (now Sandoz) not to sell a generic version of Hytrin, "thereby violating Section 1 of the Sherman Act."  Abbott successfully defended itself in the district court by invoking Noerr-Pennington immunity, which protects petitioning the government from antitrust liability.

    RELATED READING:

    NOTE:  Thanks to David Balto for providing a copy of the Hytrin brief.

  • Supreme Court Reshapes Declaratory Judgment Jurisdiction in Patent Cases

    MedImmune v. Genentech et al., 549 U.S. ___ (2007)

    The U.S. Supreme Court handed down its highly anticipated decision in MedImmune v. Genentech today, holding by an 8-1 majority that a patent licensee is not required to terminate its license agreement before seeking a declaratory judgment that the subject patent is invalid, unenforceable, or not infringed.  (Click here for opinion; click here for dissent; click here for syllabus.)  Consistent with the Court's recent suspicion of patent quality generally, this decision will make it much easier for parties to challenge the validity of patents in court.

    The Petitioner, MedImmune, manufactures Synagis, a drug used to prevent respiratory tract disease in infants.  MedImmune entered into a license agreement with respondent, Genentech, that covered an existing patent ("Cabilly I") relating to the production of chimeric antibodies, as well as a pending patent application ("Cabilly II") relating to coexpresion of immunoglobulins in host cells.

    When Cabilly II issued as a patent, in 2001, Genentech sent a letter to MedImmune stating that Synagis was covered by it and therefore MedImmune owed royalties.  MedImmune, however, believed the Cabilly II patent was invalid and unenforceable, and therefore thought it should not owe any royalties.  Nevertheless, MedImmune considered Genentech's letter to be a clear threat to enforce the Cabilly II patent, and rather than risk treble damages, attorney fees, and an injunction prohibiting the sale of Synagis (which has accounted for 80% of MedImmune's sales), MedImmune paid the royalties to Genentech "under protest and with reservation of all its rights."

    MedImmune proceeded to sue Genentech for a declaratory judgment that the Cabilly II patent was invalid, unenforceable, and not infringed by MedImmune's sales of Synagis.  However, the district court dismissed MedImmune's complaint based on the Federal Circuit's decision in Gen-Probe v. Vysis (Fed. Cir. 2004), which held that a patent licensee in good standing cannot establish an Article II case or controversy with regard to validity, enforceability, or scope of the patent because the license agreement "obliterates any reasonable apprehension" of suit.  The Federal Circuit affirmed the district court, also relying on Gen-Probe.

    Now that the Supreme Court has reversed the Federal Circuit, the case will be remanded and MedImmune will have its day in court.  Moreover, the Federal Circuit will be forced to reexamine its "reasonable apprehension of suit" test for declaratory judgment jurisdiction in patent cases, at least insofar as it applies the test to licensees.  It remains to be seen whether the Federal Circuit will go further than that, and perhaps discard the reasonable apprehension test entirely.

    RELATED READING:

  • LSI’s Biotechnology 2007 Conference, January 28-29, 2007, San Francisco

    Law Seminars International will present its “Biotechnology 2007: Key Legal and Business Developments” conference January 28-29, 2007, in San Francisco.  Speakers include outside and inside counsel, biotechnology industry executives, and financiers.

    The first day of the conference will focus on legal developments important to the biotechnology industry, while the second day will focus on business and financing issues.  Specific talks of interest include:

    • “New Developments and the Realities of Dealing with the FDA in Today’s Regulatory Environment”
    • “Is a Thriving Generic Biotechnology Industry Just Around the Corner?” (which I’ll be presenting)
    • “Recent Federal Circuit and Supreme Court Cases Affecting Biotech Companies”
    • “Understanding the Venture Capital Climate for Biotechs Today:  What Are VC’s Looking For?”
    • “Comprehensive IP Strategies: Understanding the Ins and Outs of Your IP”

    The full program is available here.  Additional details and registration information are available on the conference website.

  • Federal Circuit Sides With Abbott in Biaxin XL Case Against Andrx

    Abbott Labs. v. Andrx Pharms. et al., No. 06-1101 (Fed. Cir. 2006)

    Abbott Labs is fending off multiple generic challenges to Biaxin XL (clarithromycin extended-release tablets), an antibiotic with annual sales of over $300 million in the United States.  Companies that have filed ANDAs for generic versions of Biaxin XL include Ranbaxy, Teva, Andrx, Roxane, and Sandoz.

    In Abbott’s case against Teva, Abbott lost a motion for a preliminary injunction on grounds that its patents on Biaxin XL were likely invalid.  Shortly after the Federal Circuit affirmed that decision, Abbott and Teva reached a settlement.  In Abbott’s case against Ranbaxy, the district court held that two of Abbott’s patents were likely unenforceable.  Now, in a unanimous opinion released last Friday, the Federal Circuit has affirmed a preliminary injunction that Abbott won against Andrx.

    On appeal, Andrx presented two main arguments:  (1) based on the findings made in Abbott’s cases against Teva and Ranbaxy, Abbott was collaterally estopped from asserting the patents in suit against Andrx; and (2) given the district court’s construction of the claim term "pharmaceutically acceptable polymer," Andrx’s generic version of Biaxin XL does not infringe the claims under the doctrine of equivalents.

    With regard to Andrx’s first argument, the Federal Circuit found that in the Teva and Ranbaxy cases, "the district court judge did not intend to ‘firmly and finally resolve the issue’ for which preclusion is asserted," as required by the Supreme Court’s Blonder-Tongue decision.  Furthermore, the court found that this case did not "present the rare circumstance in which a determination made during a preliminary injunction is sufficiently final to be accorded preclusive effect."  Therefore, the court held that Abbott was not collaterally estopped from asserting the patents in suit against Andrx.

    In addressing Andrx’s noninfringement argument, the Federal Circuit first reviewied the district court’s construction of the claim term "pharmaceutically acceptable polymer."  The court found that the district court contrued this term too narrowly, in part because it read Markush group language from the specification into the claim:

    The term ‘Markush group’ does not have any meaning within the context of a written description of a patent and therefore to the extent the district court relied on the Markush group language to limit its construction to the compounds listed in the written description, it erred.

    The court then proceeded to reject Andrx’s noninfringement position, which was based on the "specific exclusion principle" and the "doctrine of claim vitiation."  Accordingly, the court found that Andrx’s generic Biaxin XL formulation could be shown to be equivalent to Abbott’s claimed formulation.

    RELATED READING:

  • New Academic Work Sheds Light on Big Pharma Patenting Activity, Reverse Payment Settlements

    People in academia seem more interested lately in the activities of the pharmaceutical industry.  Kyle Jensen, a Research Affiliate at the Harvard-MIT Division of Health Sciences & Technology, and C. Scott Hemphill, an Associate Professor of Law at Columbia, recently contacted me and let me know about their work.

    Dr. Jensen and his group analyzed drug approval and patent data since 1982 to learn how the pharmaceutical industry uses patents.  Their findings include:  most approved drugs are protected by very few patents (2.69 patents on average); "platform technologies" are rare (most patents cover only one approved drug); drug companies are generally self-sufficient (the NDA filer owns all of the patents listed for a given NDA 60% of the time), but collaboration is still necessary; and certain families of drugs are protected by "patent thickets."  Dr. Jensen’s work can be read by clicking here.

    Prof. Hemphill is interested in reverse payment settlements of Hatch-Waxman litigation, in which the innovator company pays the generic company to delay launching its generic drug.  Prof. Hemphill calls these "pay-for-delay" settlements.  His analysis of the Hatch-Waxman Act reveals that certain features of the Act widen the potential for anticompetitive harm from pay-for-delay settlements and that the Act reflects a congressional preference for litigated patent challenges over negotiations between litigants.  Prof. Hemphill reaches a conclusion that is even more strongly anti-settlement than the FTC’s position:  "a settlement should be accorded a presumption of illegality as an unreasonable restraint of trade if the settlement both restricts the generic firm’s ability to market a competing drug and includes [any] compensation from the innovator to the generic firm."  Prof. Hemphill’s paper can be read by clicking here.

    Both Dr. Jensen and Prof. Hemphill would welcome any feedback about their work.

  • Savient Loses Motion for Preliminary Injunction in Oxandrin Case, Launches Authorized Generic, and Halts Promotion of Branded Oxandrin

    Savient Pharms. v. Sandoz, No. 07-1081 (Fed. Cir.)

    On December 28, 2006, the Federal Circuit Court of Appeals denied Savient Pharmaceuticals’ motion for a preliminary injunction, pending appeal, to prevent Sandoz and Upsher-Smith from marketing their generic Oxandrin (Oxandrolone) products.  Oxandrin, with annual sales of $60 million, is indicated for the promotion of weight gain following extensive surgery, chronic infection, or severe trauma.

    Savient appealed an earlier district court decision and had moved the Federal Circuit for a preliminary injunction, pending that appeal.  Although Savient may still pursue its appeal if it so chooses, the December 28th Order left Sandoz and Upsher-Smith free to launch their generic Oxandrin products.

    In response to the Federal Circuit’s decision, Savient announced in a December 29 press release that Watson Pharmaceuticals has launched an A-B rated authorized generic of oxandrolone tablets.  Additionally, Savient announced in a press release today that it "will discontinue its 19 person Oxandrin field sales force."  It appears that Savient is content to profit from its authorized generic deal with Watson, and will cease promotion of the branded product.

    RELATED READING:

  • ACI’s 3rd National Conference on Life Sciences IP Due Diligence, January 22-23, 2007, San Francisco

    American Conference Institute has announced that its 3rd National Conference on Life Sciences IP Due Diligence will take place in San Francisco on January 22-23, 2007.

    This event features leading IP practitioners and experienced in–house counsel from the West Coast who will address some of the unique challenges facing companies when conducting IP due diligence, including such important matters as:

    • PTO reform and new case law;
    • preparing for a future due diligence review from the target’s perspective;
    • creating a checklist;
    • protecting attorney-client privilege;
    • and performing Freedom to Operate searches.

    The event features special sessions on “Getting the Target’s House in Order” and “Conducting Due Diligence from the Suitor’s Perspective.”  In addition, there will be a panel on “Real Life Case Studies Where the Due Diligence Went Terribly Wrong.”

    Additional details are available on the conference website.