Orange Book Blog

At the intersection of Patent and FDA Law

Recent Posts

  • Sandoz Requests TRO to Block FDA Approval of Generic Zocor Tomorrow

    Bloomberg News is reporting tonight that Sandoz, the generics arm of Novartis AG, filed a request for a temporary restraining order today in an attempt to prevent the FDA from granting Ivax and Ranbaxy final approval tomorrow to market generic Zocor (simvastatin).

    The motivation behind Sandoz’s eleventh hour request is not entirely clear, especially because it appears from the FDA website that Sandoz does not have an ANDA on file to market its own generic version of Zocor.  In the Bloomberg News article, Sandoz seems to explain that it filed its TRO request in order to avoid a precedent that might affect other ANDA approvals in the future.  However, that justification seems suspicious–the FDA has appealed the district court decision that effectively ordered the FDA to grant final approval to Ivax and Ranbaxy, and the appeal is on an expedited schedule.  If the FDA’s appeal is successful, the precedent Sandoz fears would be avoided.

    Besides Ivax and Ranbaxy, the other simvastatin ANDA applicants are Aurobindo, Cobalt, and Teva.  Ivax is itself a unit of Teva.

    According to the Bloomberg News article, a hearing is scheduled for 10 a.m. tomorrow in the U.S. District Court for the District of Columbia to decide Sandoz’s request for a TRO.  Teva says it will vigorously fight Sandoz’s request.

    UPDATES:

  • Merck Launches Pre-Emptive Strike Against Generic Zocor

    In advance of Merck’s patent on Zocor expiring tomorrow (Friday), and the expected launch of generic versions of Zocor by Ivax (a Teva unit) and Ranbaxy, Merck has made deals with some insurance companies to sell branded Zocor for less than Ivax and Ranbaxy planned to charge for their generics.  Teva’s stock price dropped about 10% yesterday on the news.  And Sen. Charles Schumer (D-NY) announced that he has written a letter to the FTC, requesting an investigation of Merck.

    With Zocor going off-patent, Merck had already planned to stem its losses by cutting a deal with Dr. Reddy’s to sell an authorized generic version of Zocor.  Now, in this new strategy (new to me, at least–please let me know if you’ve heard of it before), Merck plans to take on the generics directly by offering its branded drug for less than the generics.

    Many good articles have been written about this in the last couple days.  Here are a few:

    Also, an Israeli business website, Globes, has published this very interesting interview with Teva CEO Isreal Makov regarding Merck’s surprising move.

  • Bill Proposed in House to Provide Escape for Late Patent Term Extension Filings

    After a Massachusetts drug company missed–by a single day–a non-extendable deadline for filing for a patent term extension, H.R. 5120 was recently proposed in the U.S. House of Representatives to amend 35 U.S.C. 156, the statute governing patent term extensions based on regulatory review delay.  Some people are calling H.R. 5120 the "Dog Ate My Homework Act."

    Under the current version of 35 U.S.C. 156, a patent applicant has 60 days after approval under the relevant regulatory review (generally FDA review and approval of new drugs) in which to submit an application to the U.S. Patent Office for patent term extension; no allowance is made for a late filing.  H.R. 5120 would amend 35 U.S.C. 156 to provide the U.S. Patent Office with discretion in accepting late applications, so long as (a) the application was filed within 5 days after expiration of the 60-day period, and (b) the delay was unintentional.

    As drafted, the amendment would go into effect on the day of its enactment, and would apply not only to applications for patent term extension pending on or filed after the date of enactment, but also to those applications which are "the subject of a request for reconsideration of a denial of a patent term extension," such as the Medicine Company's, or which have "been denied a patent term extension . . . in which the period for seeking reconsideration of such denial has not yet expired."

    The 2005 Medicines Company annual report indicates that the company continues to explore alternatives to extend the term of the patent.  If enacted as proposed, H.R. 5120 might be such an alternative.

    The Medicines Company, based in Massachusetts, licensed a patent owned by Biogen covering the drug Angiomax and its use in preventing blood clots from forming during angioplasty.  The Medicines Company application for a patent term extension was filed on the 61st day following FDA approval of Angiomax; as a result, the U.S. PTO denied the request for patent term extension.  The Medicines Company has filed a request for reconsideration of the application for patent term extension.  A copy of the file history of the relevant patent, including the application for patent term extension, decision on the petition, and request for reconsideration, can be found here.

    The House bill was sponsored by Representative Jenkins (TN), and co-sponsored by Representatives Andrews (NJ), Delahunt (MA), Frank (MA), Hyde (IL), Meehan (MA), Sessions (TX), Boucher (VA), Duncan (TN), Gallegly (CA), Jones (OH), and Rothman (NJ).  The bill has been referred to the House Committee on the Judiciary.

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  • FTC Files Supplemental Brief in FTC v. Schering, in Supreme Court

    The FTC last week filed a supplemental brief in the Supreme Court, in response to the Solicitor General’s brief, in FTC v. Schering.  The case involves the legality of "reverse payment" settlements–those from an innovator drug company to a generic drug company–in Hatch-Waxman cases.  The Solicitor General, whose views on the case were requested by the Supreme Court, argued in his brief last month that the Court should deny FTC’s petition for certiorari.  Now, in its supplemental brief, the FTC takes issue with many of the Solicitor General’s arguments.

    The FTC argues forcefully that the Solicitor General failed to appreciate the practical effects of allowing reverse payment settlements of Hatch-Waxman litigation.  According to the FTC, "the economic impact of the ruling below on consumers of prescription drugs–including the States–is staggering.  Indeed, billions of dollars in added prescription drug costs annually are at stake."

    Nevertheless, the FTC seems to acknowledge the Solicitor General’s point that other reverse payment cases may be more appropriate for Supreme Court review.  In a footnote in its Supplemental Brief, the FTC states:  "In light of the pendency of the petition for rehearing in Tamoxifen [in the 2nd Circuit], and the possibility of the filing of a petition for certiorari in that case, the Court may wish to hold the present case pending final resolution of that case."  Links to the briefs in the Tamoxifen case are provided below.

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  • Supreme Court Denies Certiorari in SKB v. Apotex

    Following the Solicitor General’s advice, the Supreme Court today denied SmithKline Beecham’s petition for certiorari in SKB v. Apotex, No. 05-489.  The issue presented was whether inherent anticipation occurs only when one of skill in the art recognizes the prior creation of the invention.  The Federal Circuit had held that inherent anticipation may occur regardless of such recognition.

    The case concerns Apotex’s application to market a generic version of Paxil.  Apotex has been on the market with its generic Paxil since 2004.

    RELATED READING:

  • SDNY: Orange Book Listing Does Not Provide Notice Under Patent Marking Statute

    In a case of first impression, the U.S. District Court for the Southern District of New York held, on cross motions for summary judgment regarding available remedies, that an Orange Book listing of patents protecting an approved drug was not effective public notice under the patent marking statute, 35 U.S.C. 287(a).  Merck & Co. v. Mediplan Health Consulting, No. 05 Civ. 3650 (S.D.N.Y. June 14, 2006).  As a result, the damages available to Merck were limited to those accruing after the date on which the lawsuit was filed, rather than those accruing after the date on which Merck listed the patent in suit in the Orange Book.

    The case involves Mediplan's operation of an on-line Canadian pharmacy that offered a generic version of Zocor (simvastatin) for sale to U.S. customers, prior to expiration of Merck's simvastatin patents.  Mediplan apparently did not file an ANDA, as is required for FDA approval of generic drugs in the U.S.  Merck sued Mediplan for infringement of U.S. Patent No. 4,444,784, which included both composition and method claims to simvastatin.  As required under the Hatch-Waxman Act, Merck listed the '784 patent in the Orange Book.

    It was undisputed at trial that Merck failed to "mark" its Zocor product, as called for by 35 U.S.C. 287(a).  Merck asserted only the method of use claims against Mediplan, and argued that it was not required to comply with the marking requirement, which does not apply to patents for only a method or process, since no physical item exists to be marked.  The court held that marking is required where the patent includes both composition and method claims, even if only the method claims are asserted.

    The court then turned to Merck's argument that its Orange Book listing served as effective public notice under the marking statute.  The court noted the lack of precedent in the case, and proceeded to focus its analysis on the judicial interpretation of the marking statute as requiring a specific infringement charge against a specific product, and that general statements to the industry about the patent's existence do not meet this standard.  The court, finding that the Orange Book "is merely a catalog that informs the public of the patent's existence," held as a matter of law that Orange Book listing of the simvastatin patents was not adequate notice under the marking statute.

    In rebutting Merck's arguments that the Orange Book is not just a generalized warning, the court noted that Merck did not send a copy of the relevant listing to Mediplan, or reference Mediplan or their products.  The court rebuffed Merck's policy arguments, as beyond the appropriate inquiry of the court.

    The court's ruling is sure to raise eyebrows.  Orange Book listing of patents covering an FDA-approved drug is required under federal law.  The listing regulations make clear that the drug maker can list only those patents on which it could reasonably sue a third party for patent infringement for making or using the drug without the drug maker's approval.  Generic drug manufacturers seeking to gain FDA approval to market a generic version of an FDA-approved drug are required to make a certification with respect to patents listed in the Orange Book for the relevant FDA-approved drug.

    Thus, any generic manufacturer operating within federal law is required to consult the Orange Book prior to filing its ANDA to determine whether its manufacture of a specific drug is likely to result in patent infringement, and will identify the relevant listed patents.  This certainly would appear to provide notice of the existence of patents covering the drug, as required under the patent marking statute.  It is not clear why a generic manufacturer operating outside the federal scheme for generic drug approval, like Mediplan in this case, should benefit by avoiding review of the Orange Book listings for drugs they intend to market in the United States.

  • Merck and Integra Submit Post-Hearing Letters to Federal Circuit, Urging the Court Not to Address Research Tools Issue

    As reported in a post last week, the Federal Circuit recently heard oral arguments in Merck KGaA v. Integra LifeSciences following remand from the Supreme Court.  Since the hearing, both Merck and Integra have submitted letters to the Federal Circuit, urging the court not to decide the issue of whether Merck’s use of Integra’s patented compounds fell outside the 271(e)(1) FDA exemption as "research tools," in which case Merck would be liable for patent infringement.

    Merck asserted in its letter that a Federal Circuit decision based on the research tool issue would be improper because Integra never argued–in the district court, Federal Circuit, or Supreme Court–that the jury verdict for Integra should be sustained on the basis that Merck used Integra’s patented compounds as research tools.  Integra, in its own letter, agreed with Merck, stating that while the research tool question is extremely important, it should be answered in a case in which the issue has been "squarely raised and thoroughly vetted" in the trial court.

    At oral argument, Judge Rader, in particular, seemed gung ho to remand the case to the district court to determine whether Merck used Integra’s compounds as research tools and therefore was not entitled to the 271(e)(1) FDA exemption.  If the other two members of the panel, Judges Newman and Prost, follow the parties’ advice and ignore that issue, then the Federal Circuit will limit its opinion to the narrower technical question of whether Merck’s JMOL motion was properly denied by the district court.

    NOTE:  Thanks to Dennis Crouch for providing the parties’ letters!

  • Barr Labs Pays $22.5 Million to Sandoz to Settle Antitrust Case Involving Warfarin

    Barr Labs announced today in a press release that it has paid $22.5 million to settle antitrust claims brought in 1998 by Invamed and Apothecon, both of which are subsidiaries of Sandoz.  The settlement comes on the same day that a trial in the case was scheduled to begin in the Southern District of New York.

    The plaintiffs’ allegations stem from a 1995 exclusive supply agreement between Barr and ACIC/Brantford for clathrate, the primary raw material used to make warfarin.  According to the plaintiffs, the agreement delayed their market entry for 16 months because ACIC/Brantford was the only supplier of clathrate at the time.  Because of the agreement Barr was able to launch its generic warfarin product before the plaintiffs, and locked up much of the market as the first mover.

    In May 2002, the district court (Sweet, J.) granted summary judgment to Barr on the plaintiffs’ antitrust claims of monopolization.  However, the court also held that the plaintiffs could proceed to trial on their state law claims of tortious interference with contract.  In October 2004, the Second Circuit reversed the district court’s grant of summary judgment, holding that the plaintiffs’ antitrust claims should also be heard.

    RELATED READING:

  • FTC Publishes Public Comments on its Authorized Generics Study

    The FTC has begun posting public comments relating to its proposed authorized generics study on its website.  The public comment period ended Monday.

    In addition to the comment by the Ohio Public Employees Retirement System, available on the FTC website, a helpful reader provided comments from the following consumer and public interest groups:

    All of the comments made available so far encourage the FTC to proceed with its study, and even to broaden the study’s scope to investigate other allegedly anticompetitive practices in the pharmaceutical industry.

    The FTC is expected to update its website by posting additional comments in the coming days and weeks.  The FTC plans to complete its study in 2007.

    RELATED READING:

  • Federal Circuit Hears Oral Arguments in Integra v. Merck, After Remand from Supreme Court

    A Federal Circuit panel of Judges Newman, Rader, and Prost heard oral arguments Monday in Integra LifeSciences v. Merck KGaA, No. 02-1052.  An mp3 audio file of the 45-minute session is available here (be patient when downloading this; it’s a 40 mB file).

    The case involves the scope of the "FDA exemption" under 35 U.S.C. 271(e)(1), which exempts activities "reasonably related to the development and submission of information" to the FDA from charges of patent infringement.  Last year, the Supreme Court reversed the Federal Circuit’s earlier decision in the case, and remanded it to the Federal Circuit for further proceedings.  The Supreme Court held that the FDA exemption "extends to all uses of patented inventions that are reasonably related to the development and submission of any information under the FDCA," including all clinical and preclinical studies of patented compounds appropriate for submission to the FDA.

    At this stage of the proceedings, Merck stated the issue as follows:

    The Supreme Court has now clarified that the FDA exemption immunizes an experiment from patent infringement claims where (1) it is reasonable for a scientist to believe that a drug candidate "may work through a particular biological process, to produce a particular physiological effect"; and (2) the experiment "uses the compound in research that, if successful, would be appropriate to include in a submission to the FDA."  There is no dispute that, by the time Scripps scientists conducted the accused experiments at issue here, Merck and Scripps had discovered that the accused compounds shrank tumors in animals, and that every accused experiment was reasonably designed to yield data on topics that the Supreme Court has confirmed are relevant to the FDA.  Should judgment be entered as a matter of law?

    The oral arguments grew heated early, with intense questioning by Judge Rader focusing on whether "research tools" are protected by the FDA exemption under the Supreme Court’s decision.  Judge Rader called this the "central issue we’re going to be dealing with here."  Merck’s attorney tried to refocus the court on whether Merck’s specific experiments with Integra’s patented compounds are entitled to the FDA exemption (arguing they are), saying, "I’ve only got 10 more minutes."  But Judge Rader would have none of it, replying, "You’re going to spend them on this issue, so you might as well get used to it."

    The question whether research tools fall under the FDA exemption is especially important to small biotechnology companies.  The Supreme Court decision left this question unanswered.

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