Orange Book Blog

At the intersection of Patent and FDA Law

Recent Posts

  • Is a Patent that is Subject to a Terminal Disclaimer Eligible for a Patent Term Extension?

    It has always been assumed the answer is "yes."  Now the Federal Circuit will answer the question directly in Merck v. Hi-Tech Pharma., which concerns Hi-Tech’s ANDAs for generic versions of Merck’s Trusopt and Cosopt prescription eye drops.  The case was argued in December and a decision could come at any time.

    Merck owns U.S. Patent No. 4,797,413, covering dorzolamide, the active ingredient in Trusopt and Cosopt.  The ‘413 patent issued from a continuation-in-part application that claims priority from Merck’s U.S. Patent No. 4,677,115.  During prosecution of the ‘413 patent, the patent examiner rejected the claims for "obviousness-type double patenting," explaining that the claims were not patentably distinct from those of the earlier issued ‘115 patent because they "include position isomers and adjacent homologs to the previously allowed prior art compounds which are obvious variations in view thereof."  To overcome the rejection, Merck filed a terminal disclaimer, disclaiming "the terminal part of any patent granted on [the application] which would extend beyond the expiration date of U.S. patent 4,677,115, that is, June 30, 2004."

    The FDA approved Merck’s NDA for Trusopt in 1994, after several years of FDA regulatory review.  Due to the lengthy review process, the FDA granted Merck a patent term extension under 35 USC 156, thereby extending the term of the ‘413 patent to April 28, 2008.  Section 156 was enacted as part of the Hatch-Waxman Act (it is the "Patent Term Restoration" part) in a trade between innovator and generic drug companies: innovators could obtain patent term extensions and generic drug companies could develop their drug products before patent expiration.  Under Section 156, NDA holders may choose one patent for patent term extension per approved drug.  Presumably, Merck sought an extension of the ‘413 patent rather than the ‘115 patent because its claims are stronger.

    After Hi-Tech filed ANDAs for generic versions of Trusopt and Cosopt, Merck sued Hi-Tech for infringement of the ‘413 patent.  As its only defense, Hi-Tech asserted that the patent term extension on the ‘413 patent was invalid due to the terminal disclaimer that Merck voluntarily filed on the patent.  On April 25, 2006, the district court entered final judgment on the pleadings in Merck’s favor and enjoined Hi-Tech from selling generic dorzolamide products until the ‘413 patent expires.  Hi-Tech promptly appealed to the Federal Circuit, presenting the following issue for review:

    Whether a terminal disclaimer voluntarily filed to avoid double patenting, as a matter of law, precludes or disclaims the right to a patent extension under 35 USC 156 that would permit the disclaimed patent to be enforced after expiration of the earlier patent that gave rise to the disclaimer.

    According to Hi-Tech, "[t]his case arises solely because the PTO regulation implementing 35 USC 156 added words to the statute which are not there."  Thus, the arguments in the appeal center on the proper statutory interpretation of Section 156.  Hi-Tech argues that the district court misinterpreted Section 156 as overturning settled law on the irrevocable nature of terminal disclaimers.  Merck argues, on the other hand, that the structure, legislative history, and "twenty years of consistent PTO interpretation of Section 156" support the district court’s "plain language construction" of the statute that allowed the patent term extension on the ‘413 patent to stand.  Thanks to the attorneys who argued the case, links to the briefs are provided below.

    A decision in favor of Hi-Tech would have far-reaching consequences.  Many of the most valuable patents owned by innovator drug companies would lose years off their terms, potentially costing billions of dollars in lost revenue.  Innovator drug companies routinely file for patent term extensions, and terminal disclaimers are quite common simply due to the nature of pharmaceutical patenting.

    LINKS TO APPEAL BRIEFS:

  • JAMA Report Finds Economic Benefits of FDA Pediatric Exclusivity Program Vary Widely

    A recent report published in the Journal of the American Medical Association found that the FDA’s Pediatric Exclusivity Provision (PEP) does not necessarily yield lucrative returns for innovator drug companies.

    The PEP authorizes the FDA to grant innovator drug companies a six-month extension of marketing exclusivity (beyond patent expiration) in exchange for conducting studies of the drug’s effect in children.  The program sought to improve product labeling for pediatric uses.  The provision, passed as part of the Food and Drug Administration Modernization Act of 1997, is set to expire later this year.

    Critics have alleged that the PEP generates a lucrative windfall for innovator drug companies, while providing consumers with few additional benefits.  The JAMA report examined the degree to which Big Pharma has financially benefited from the program.

    The authors studied nine different drugs in a variety of therapeutic classes.  The six-month net economic return for the participating drug company varied from -$8.9 million to $507.9 million.  The return-to-cost ratios varied from -0.68 to 73.63.

    The authors found that the PEP did not consistently generate large financial returns for innovator drug companies.  In some instances, complying with the program generated a net loss.  Yet the authors found that the program has created incentives for innovators to carry out much-needed clinical drug trials in children.

    Robert S. Dailey is a third-year law student at the University of North Carolina at Chapel Hill.  He holds a Ph.D. in physical chemistry.  Rob was a member of the 2006 class of summer associates at McDonnell Boehnen Hulbert & Berghoff.

    RELATED READING:

  • Bill Aimed at Prohibiting Reverse Payment Settlements Clears Senate Judiciary Committee

    The Senate Judiciary Committee passed the "Preserve Access to Affordable Generics Act" (S. 316) today by unanimous consent.  If enacted, the bill would prohibit "reverse payment" settlements of Hatch-Waxman litigation, in which an innovator drug company pays a generic drug company to delay marketing its generic drug product.  Specifically, the bill would amend the Clayton Act by adding a new Section 28, reading in part:

    (a) It shall be unlawful under this Act for any person, in connection with the sale of a drug product, to directly or indirectly be a party to any agreement resolving or settling a patent infringement claim in which–

    (1) an ANDA filer receives anything of value; and

    (2) the ANDA filer agrees not to research, develop, manufacture, market, or sell the ANDA product for any period of time.

    (b) Nothing in this section shall prohibit a resolution or settlement of a patent infringement claim in which the value paid by the NDA holder to the ANDA filer as a part of the resolution or settlement of the patent infringement claim includes no more than the right to market the ANDA product prior to the expiration of the patent that is the basis for the patent infringement claim.

    The bill is thus a legislative solution to reverse payment settlements, which have been endorsed by federal courts in cases such as FTC v. Schering and In re: Tamoxifen Citrate Antitrust Litigation.  The FTC has been a vocal critic of such decisions.

    RELATED READING:

  • Follow-on Biologics Bill Reintroduced in Congress

    Most pharmaceuticals made using biotechnology are approved through a Biologic License Application (BLA) rather than a New Drug Application (NDA).  The FDA requires essentially the same type of evidence for both biologics and conventional (i.e., small molecule) drugs; namely, results of adequate and well-controlled clinical trials demonstrating safety and effectiveness.  However, currently there is no abbreviated pathway for the approval of generic, or “follow-on”, biologics like the Abbreviated New Drug Application (ANDA) pathway for the approval of conventional drugs.

    The “Access to Life-Saving Medicine Act,” reintroduced by Rep. Waxman, Sen. Schumer, and other lawmakers yesterday in the House and Senate, would establish an abbreviated approval process for follow-on biologics.  According to an AP story out today, a new report by Express Scripts, a pharmacy benefits manager, finds that generic biotech drugs could save patients and insurers $71 billion over 10 years.  This report from the Pharmaceutical Care Management Association, an industry trade group for pharmacy benefits managers, says Medicare Part B would save $14 billion dollars over that time.  Pharmacy benefits managers earn big profits from generic drugs.

    Rep. Waxman’s website contains a great deal of information on this issue, including a background on biologics, a summary of the proposed Act, and the full text of the Act.  Additionally, the website contains letters of support from the generic drug industry, consumer groups, and insurance companies.  Another perspective is offered by the Biotechnology Industry Organization, which represents innovator pharmaceutical and biotechnology companies.  BIO’s website has a section devoted to the issue of follow-on biologics, and contains information on developments in Europe as well as the United States.

    UPDATE:  22-Feb-07 BIO response to Express Scripts and PCMA studies

  • District Court Upholds Johnson & Johnson’s Topamax Patent, Keeping Mylan’s Generic Off the Market

    Ortho-McNeil Pharma. v. Mylan Labs. et al., No. 04-1689 (D. N.J. 2007)

    Mylan Laboratories filed an ANDA in 2001 to market a generic version of Topamax (topiramate), Johnson & Johnson’s blockbuster anticonvulsant drug, and asserted that the patent on Topamax was invalid due to obviousness.  As we previously reported, last October Judge Stanley R. Chesler of the U.S. District Court for the District of New Jersey preliminarily enjoined Mylan from selling generic Topamax, pending a final resolution of the case.  Now, Judge Chesler has granted J&J’s motion for partial summary judgment of patent validity, finding that J&J’s U.S. Patent No. 4,513,006 is not invalid as obvious.

    Judge Chesler’s opinion on summary judgment tracks his October opinion granting a preliminary injunction.  In both decisions, Judge Chesler applied the Federal Circuit’s "motivation-suggestion-teaching" test for obviousness.  That test, which is currently under review by the Supreme Court in KSR v. Teleflex, requires evidence of a teaching, suggestion, or motivation to combine or modify prior art references before making a finding of obviousness.

    The ‘006 patent covers the drug topiramate, pharmaceutical compositions containing topiramate, and a method of using topiramate to treat convulsions.  Topiramate is an inhibitor of fructose-1, 6-bisphosphatase (FBPase), a key enzyme in glucose metabolism.  Mylan asserted that the inventors sought to discover a FBPase inhibitor as a potential treatment for diabetes, and thereafter arrived at topiramate.  According to Judge Chesler, however:

    Mylan has offered no evidence that there was a suggestion from any source to use FBPase inhibitors to solve the problem of controlling blood sugar in diabetic patients; the requirements of the the "motivation-suggestion-teaching" test have not been met.  Federal Circuit law requires "rigorous application" of this test in an obviousness analysis.  Mylan has not shown a genuine issue as to any material fact; rather, there is a complete failure of proof concerning an essential element of the nonmoving party’s case.

    The ‘006 patent will not expire until September 26, 2008.  If Mylan wishes to market its generic Topamax before then, it seems that it will have to appeal to the Federal Circuit.

    UPDATES:

  • Watson Pharmaceuticals and GlaxoSmithKline Settle Patent Suit Over Wellbutrin XL

    Watson Pharmaceuticals announced today that it has settled a patent infringement suit concerning GlaxoSmithKline’s popular antidepressant Wellbutrin XL (bupropion HCl extended release tablets) for $35 million.  The suit was filed in the Southern District of Florida in December 2005 by Andrx Pharmaceuticals, which was acquired by Watson last year.  Andrx asserted that Glaxo’s formulation for Wellbutrin XL infringed its U.S. Patent No. 6,905,708, entitled "Controlled Release Oral Dosage Form."

    Andrx is seeking to market a generic version of Wellbutrin XL and has filed an ANDA with a paragraph IV certification on the Orange Book-listed patents.  Biovail, which owns those patents and manufactures Wellbutrin XL for Glaxo, filed suit against Andrx in September, 2005 in the Southern District of New York.  The timing of Andrx’s suit against Glaxo in Florida suggests that Andrx may have sought to gain the upper hand in Biovail’s case against Andrx in New York, perhaps hoping to settle the case on terms that it would allow it to sell generic Wellbutrin XL prior to the expiration of Biovail’s patents.  The New York case appears to be proceeding, with expert discovery scheduled to end this month.

    RELATED READING:

  • Amphastar and Teva Prevail Over Aventis in Generic Lovenox Trial, But Still May Not Receive FDA Approval

    Aventis Pharma v. Amphastar Pharms., No. 03-887 (C.D. Cal. 2007)

    In a ruling issued last Friday, Judge Mariana R. Pfaelzer of the U.S. District Court for the Central District of California held Aventis’s U.S. Patent No. 5,389,618 and its U.S. Reissue Patent No. 38,743 unenforceable due to inequitable conduct.  The patents cover Lovenox (enoxaparin), a low-molecular weight heparin composition exhibiting anticoagulant properties and indicated for the prevention and treatment of deep vein thrombosis.  The drug was Aventis’s top seller as of Q3 of 2006, and was on pace to gross nearly $2 billion in U.S. sales for the year.  Amphastar and Teva have filed ANDAs for generic Lovenox, and await FDA approval.

    In 2005 the district court found the same patents unenforceable on summary judgment.  On appeal last year, the Federal Circuit affirmed the district court on the materiality prong of inequitable conduct, but remanded the case for a full trial on the intent prong.  Friday's ruling follows a five day bench trial on that issue, held in December.

    The standard rule on inequitable conduct requires the defendant to prove materiality and deceptive intent independently by clear and convincing evidence judged by the totality of the circumstances.  Several recent Federal Circuit inequitable conduct opinions have come close to articulating what appears to be a burden shifting test for determining deceptive intent.  Last year’s Ferring v. Barr Labs. probably stands as the high-water mark.  Other cases in the same vein include Bruno Independent Living and Frazier.  When the facts of these cases are examined closely, however, it becomes clear that they signal no significant departure from the general rule.

    These recent cases all involve (i) highly misleading statements and/or omissions to the PTO, (ii) circumstances which the make the conduct appear particularly egregious, and (iii) plaintiffs who proffer no explanations for their conduct.  The rule could be stated as follows: A plaintiff whose conduct reeks of bad faith cannot avoid inequitable conduct simply by coming to court and remaining silent.  This is not burden shifting, but a gloss on how to apply the totality-of-the-circumstances test with a particular class of defendants.  After all, none the Federal Circuit’s post-Ferring opinions profess to abandon the totality-of-the-circumstances test in favor of a burden-shifting mechanism.  Moreover, the Federal Circuit has consistently held that defendants must prove more than an absence of good faith, and that plaintiffs are under no obligation to prove anything.

    But these nuances were lost on the district court when it ruled against Aventis last week.  In its analysis, the court made express use of a burden shifting test for determining inequitable conduct.  The court cited the aforementioned line of cases and took language from Paragon Podiatry (Fed. Cir. 1993), to craft a rule which would allow a defendant to shift its burden of proof simply by showing an unexplained violation of the duty of candor.  But Paragon Podiatry involved a summary judgment motion.  Of course the court used a burden shift in that instance because that is what courts are required to do in ruling on summary judgment motions.  This was a trial, however, not a mere summary judgment hearing.  The regular totality-of-the-circumstances test ought to have been used in this case.  Instead, the court shifted the burden to Aventis and largely forced the Aventis scientist to prove that he had in fact acted in good faith.  Aventis will most likely appeal the decision to the Federal Circuit.

    Even though last Friday's ruling is a blow to Aventis, it is far from clear that Aventis will be facing competition from Generic Lovenox anytime soon.  Neither Amphastar nor Teva has received approval from the FDA to market generic Lovenox and some analysts reportedly believe they never will.  Enoxaparin is a complex heterogeneous mixture of polysaccharides that is difficult to characterize and may be impossible for generic companies to replicate.  Indeed, Aventis filed a citizen petition in 2003 urging the FDA not to approve generic versions of Lovenox until enoxaparin is fully characterized or until the generic companies conduct full clinical trials to establish safety and efficacy.  The FDA has not yet ruled on Aventis's petition.

    Robert Dailey, Ph.D. is a physical chemist and a third-year law student at the University of North Carolina at Chapel Hill.  Dr. Dailey was a member of the 2006 class of summer associates at McDonnell Boehnen Hulbert & Berghoff.

    RELATED READING:

  • IQPC “Pharmaceutical & Biotech Patent Litigation Strategies 2007” Conference, March 27-28, London

    International Quality & Productivity Center has announced that its "Pharmaceutical & Biotech Patent Litigation Strategies 2007" conference will be held March 27-28, 2007, in London, England.  The conference will cover the evolving trends in both Europe and the United States.  Speakers include in-house counsel from major pharmaceutical companies as well as outside counsel who specialize in this area.

    Presentations that sound particularly interesting include:

    • The Future of Patent Life Cycle Management in Litigation;
    • Implementing Effective and Co-Ordinated Pan-European Patent Litigation Strategies;
    • Successfully Managing Global, Multi-Jurisdictional Patent Litigation;
    • Strategies for Patent Litigation in Emerging and Developing Markets;
    • Current Status of Follow-on Biologics/Biosimilars; and
    • The Interface Between IP, Competition and Regulatory Laws.

    Additionally, IQPC is offering three pre-conference master classes on March 26th:

    • Drafting Robust Patents to Withstand Litigation–Evaluating Your Portfolio;
    • Acquisition, Licensing, Litigation: How to Effectively Manage Technology Patents; and
    • Strategies and Tactics in Achieving Freedom to Operate.

    The conference website has additional information, including the full agenda, speaker biographies, and registration forms.

    Orange Book Blog is a media partner of this conference.

  • FTC Pursues Antitrust Case Against Barr Labs After District Court Denies Barr’s Motion to Dismiss

    Federal Trade Comm’n v. Warner Chilcott Holdings, No. 05-2179 (D. D.C. 2007)

    Judge Colleen Kollar-Kotelly of the U.S. District Court for the District of Columbia recently denied Barr Laboratories’ motion to dismiss a Federal Trade Commission lawsuit stemming from Barr’s agreement with Warner Chilcott concerning generic Ovcon 35.  The opinion is available here.

    In 2001, Barr Labs filed an ANDA for a generic version of Warner Chilcott’s oral contraceptive Ovcon 35, an older product no longer protected by patents.  Barr appeared to be close to receiving final approval from the FDA in late 2003.  Faced with losing a substantial amount of revenue to generic competition, Warner Chilcott agreed to pay Barr $20 million not to launch its generic product until five years after approval.

    The FTC responded by filing suit against both Warner Chilcott and Barr, alleging unfair methods of competition in violation of Section 5 of the FTC Act.  In its complaint, the FTC described the agreement between Warner Chilcott and Barr as a "horizontal agreement not to compete," which "on its face eliminates competition and has no plausible procompetitive justification," and is therefore "a naked restraint of trade."  The FTC sought an order enjoining Warner Chilcott and Barr from operating under their agreement, preventing the defendants from engaging in "similar and related conduct" in the future, and granting "such other equitable relief as the Court finds necessary to redress and prevent recurrence of defendants’ violation of Section 5(a) of the FTC Act."

    Last September, Warner Chilcott waived the exclusivity provisions of its agreement with Barr, which had prevented Barr from introducing its generic Ovcon 35.  Shortly thereafter, Barr launched its generic product.  Then, as we previously reported, Warner Chilcott reached a settlement with the FTC requiring Warner Chilcott "to refrain from entering into similar agreements in the future."  Barr, however, did not settle with the FTC.  Instead, Barr filed a motion to dismiss the FTC’s complaint as moot.

    Barr argued that the case was moot for three reasons: (1) Warner Chilcott waived the exclusivity provisions of its agreement with Barr; (2) Barr launched its generic Ovcon 35 product; and (3) Warner Chilcott agreed not to enter into similar future agreements with Barr.  The FTC opposed Barr’s motion on grounds that its complaint sought not only to enjoin Warner Chilcott and Barr from operating under their non-competition agreement, but also to prevent Barr from engaging in "similar and related conduct" in the future.

    Judge Kollar-Kotelly rejected Barr’s assertion that "there can be no reasonable expectation that the conduct at issue will be repeated," finding that "while Warner Chilcott may be enjoined from entering into similar agreements in the future, Barr–who did not enter into a settlement agreement with the FTC and is not bound by [Warner Chilcott’s settlement]–faces no such constraint.  Barr thus remains free to enter into the very type of agreement that the FTC would seek to enjoin through a permanent injunction."  Additionally, Judge Kollar-Kotelly noted that "Barr has thus far maintained that the exclusivity provisions of [its agreement with Warner Chilcott] are entirely lawful, and courts have found cases not to be moot where, as here, defendants have insisted upon the legality of the challenged practices."

    Thus, the FTC appears to be pressing ahead with its case against Barr, seeking to permanently enjoin Barr from entering agreements "similar and related" to the one it reached with Warner Chilcott.

    Thanks to Kurt Karst for providing a copy of the opinion.

  • ACI “FDA Boot Camp” Conference, March 26-27, NYC

    American Conference Institute has announced that its third FDA Boot Camp will be taking place March 26-27, 2007, in New York, New York.  According to ACI, the inaugural FDA Boot Camp conference, held in New York last March, was sold out, as was this past September’s FDA Boot Camp in Chicago.  Designed for product liability and patent litigators, as well as patent prosecutors and life sciences investment/securities experts, the conference promises to provide attendees with a strong working knowledge of core FDA regulatory competencies.

    ACI has assembled a distinguished faculty of top FDA regulatory experts that will share their knowledge and give critical insight on such topics as the organization, functions, and operations of the FDA; essentials of the approval process for drugs, biologics and devices, including NDAs, INDs and BLAs; and clinical trials for drugs and biologics and the clearance process for devices.  Demand for this conference is high and ACI expects another sell out; early registrations are recommended.  For more information on the event, visit ACI’s FDA Boot Camp web site: www.americanconference.com/fdabootcampnyc.

    Orange Book Blog is a media partner of this conference.