FDA logo.jpgOn November 13, 2012, Cumberland Pharmaceuticals Inc. (“Cumberland”) sued FDA, the Commissioner of Food and Drugs, and the Secretary of Health and Human Services in federal district court for the District of Columbia for denying Cumberland’s Citizen Petition and approving InnoPharma, Inc.’s (“InnoPharma’s”) abbreviated new drug application (“ANDA”) for an acetylcysteine injection. Cumberland asserted that the denial of the Citizen Petition and the approval of InnoPharma’s ANDA were “arbitrary, capricious, and abuse of discretion, and not in accordance with law, all in violation of the APA [Administrative Procedure Act]” and “violated the Federal Food, Drug, and Cosmetic Act (‘FDCA’),” according to its complaint.

Cumberland holds the approved new drug application (“NDA”) for the reference listed drug (“RLD”), Acetadote®, indicated to prevent or lessen hepatic injury in adults and children when administered intravenously within 8 to 10 hours after ingestion of a potentially hepatotoxic quantity of acetaminophen. The original formulation of Acetadote® contained edentate disodium (“EDTA”) as a chelating agent that was believed to be necessary for the stability of the product. FDA approved Acetadote® in January of 2004, but conditioned its approval on Cumberland’s agreement to perform post-approval studies to evaluate whether EDTA could be removed from the formulation in view of safety concerns. EDTA has been associated with a significant drop in serum calcium levels, which may result in fatality, hypokalemia, hypomagnesaemia, or hypotension as well as allergic reactions.

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Written by Shelly Fujikawa, Ph.D.

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As a result, Cumberland developed and obtained approval in January 2011 from FDA for a new EDTA-free formulation after, according to the complaint, surprisingly demonstrating that EDTA was unnecessary to maintain drug stability. Cumberland then withdrew the EDTA-containing formulation from the market.
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Thumbnail image for Thumbnail image for Thumbnail image for Thumbnail image for Thumbnail image for aci_header_banner.gifAmerican Conference Institute (ACI) will be holding its inaugural Legal, Regulatory and Compliance Guide to Orphan Drugs and Rare Diseases in Boston at the Hyatt Regency on November 28-29, 2012. This unique program features a distinguished faculty of over two dozen leading legal and regulatory orphan drugs and rare diseases experts – including the former director of FDA’s Office of Orphan Products Development, senior in-house pharmaceutical counsel, leading patient advocates, and preeminent FDA and patent attorneys – who will address the intricacies of the FDA’s orphan drug designation process as well as the challenges affecting orphan drug development and commercialization and overall patent portfolio considerations.

The ACI conference provides a comprehensive forum for the industry to discuss the latest legal and regulatory developments affecting orphan products and therapies for rare diseases and to analyze the strategic considerations in drug development aimed at providing patients facing an unmet medical need with safe and effective life changing therapy. In light of recent cases concerning FDA enforcement of orphan exclusivity, the conference will also feature a spotlight session on “Protecting Orphan Drug Designation and Proactively Guarding Against Potential Liability.”

More information about this event, including a full agenda, faculty list, and brochure can be accessed at www.AmericanConference.com/orphandrug

sleepingperson.pngLast week, FDA denied a Citizen Petition filed by Jazz Pharmaceuticals, Inc (“Jazz”). The May 18, 2012 Petition concerned bioequivalence studies relating to Xyrem® (sodium oxybate), Jazz’s oral solution indicated for the treatment of excessive daytime sleepiness and cataplexy in patients with narcolepsy. Before issuing its decision, FDA received and considered public comment from Roxane Laboratories (“Roxane”), who had an Abbreviated New Drug Application (“ANDA”) referencing Xyrem accepted for review in late 2010.

Jazz asked FDA to take three actions. First, Jazz asked FDA to immediately publish in The Orange Book bioequivalence requirements specifying whether in vitro or in vivo bioequivalence studies, or both such studies, are required for ANDAs referencing Xyrem®. Jazz claimed that FDA’s failure to have done so within the first 30 days of Xyrem®’s approval was a violation of the Federal Food, Drug, and Cosmetic Act (“FD&C Act”) (See 21 U.S.C. § 355(j)(7)(A)(i)-(ii).) and the Administrative Procedure Act (“APA”) (See 5 U.S.C. § 706.). FDA disagreed; the Agency found several flaws with Jazz’s arguments. First, requiring the publication of bioequivalence data type for ANDAs within 30 days of new drug approval would be inconsistent with other sections of the FD&C Act, as well as certain FDA regulations. Second, adopting Jazz’s arguments would require the Agency to generate and evaluate the scientific data needed to understand bioequivalence characteristics at the time the reference listed drug (“RLD”) was approved. FDA disfavored this position, because it would prevent FDA from gaining insight into the characteristics of the RLD during its marketing. Many products never face generic competition, or only do so after the development of acceptable bioequivalence methodologies. As such, FDA reasoned it would be a waste of Agency resources to determine what types of bioequivalence studies are needed within the first 30 days of the RLD’s approval. Third, there is no indication Congress meant the statute to require what Jazz sought, and no court has construed the statute as requiring as much. Finally, FDA noted that Jazz’s interpretation would actually prejudice those who the statute was meant to protect, i.e., the ANDA sponsors. Requiring FDA to publish bioequivalence requirements within 30 days of the RLD approval would diminish FDA’s ability to provide ANDA sponsors with information about the best ways to demonstrate bioequivalence.

Next, Jazz asked FDA not accept for review, review, or approve any ANDA referencing Xyrem® unless and until FDA has published bioequivalence requirements in the Orange Book specifying whether in vitro bioequivalence studies, in vivo bioequivalence studies, or both such studies, are required for ANDAs referencing Xyrem®. Jazz argued that to do so would violate the APA. The drug company reasoned that an ANDA must reference an RLD, and an RLD does not become an RLD until FDA issues the bioequivalence requirements. As such, Jazz concluded that an ANDA can only be accepted for review after FDA issues bioequivalence requirements. Accordingly, Jazz asked FDA to set aside its acceptance of Roxane’s ANDA because this was “agency action . . . without observance of procedure required by law,” “not in accordance with law,” “in excess of statutory jurisdiction, authority, of limitations,” and “short of statutory right.” Again, FDA declined. The Agency claimed that refusing to accept an ANDA on those grounds would conflict with various FD&C Act sections, including Section 505(j)(2)(A), which delineates what information is required in an ANDA and does not list the bioequivalence requirements, as well as certain FDA regulations. It also refused to accept an interpretation of the statute that would punish ANDA applicants, even if in compliance with the statutory requirements, for FDA’s failure to publish the bioequivalence requirements.
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Thumbnail image for Thumbnail image for Thumbnail image for Thumbnail image for aci_header_banner.gifAmerican Conference Institute’s 2nd Comprehensive Guide to Patent Reform once again unites experienced in-house counsel from top innovators, private practice experts, and senior officials from the USPTO to answer patent professionals’ most pressing questions, including:

  • What does “first to file” actually mean under the AIA requirements? Which system can you or should you file under – the current first to invent or the new first to file (or both)? And how do you avoid first-to-file bubble filings before 3/15/2013?
  • When can on-sale and public use activity be considered prior art? Has secret §102(f) prior art been eliminated?

Thumbnail image for ITC.bmpOn November 7, 2012, FLH Partner Brian J. Malkin and Associate Christopher Gosselin were in attendance at this year’s International Trade Commission Trial Lawyers Association Annual Meeting at the International Trade Commission (“ITC”) in Washington, D.C. The theme of this year’s meeting was the enforcement of ITC exclusion orders at the border, and the relationship between customs and the ITC.

ITC Chairman Irving A. Williamson opened the meeting, stressing his commitment to reducing the overall length of Section 337 Investigations from 16 months to 13.5 months. He also promised to continue efforts to reign in the cost of discovery during Section 337 Investigations.

During the refreshment break, guests were invited to view the new courtroom on the second floor, and heard brief remarks from Chief Administrative Law Judge (“ALJ”) Charles E. Bullock. The new courtroom is spacious and well equipped with modern technology ranging from video projection screens to LCD monitors at every table. The courtroom should see plenty of use once it opens for business, as even with the new courtroom, the ITC still has more ALJs than available space. Although the ITC saw a 30% decrease in newly instituted investigations in 2012 after a record setting number in 2011, the ALJs continue to manage a near record level of active investigations.
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gavelgold.jpgK-V Pharmaceutical Company (“K-V”) has taken the fight over its preterm-birth prevention drug, Makena® (17-hydroxypreogesterone caproate solution) (“HPC”), to the International Trade Commission (“ITC”). In its complaint, K-V asks the ITC to: (1) issue a temporary general exclusion order prohibiting any unauthorized importation of HPC and (2) issue a temporary cease and desist order stopping owners, importers, and consignees from importing, selling, offering for sale, distributing, or soliciting any HPC unless authorized by K-V.

K-V states that its merits argument will focus on the importation of HPC for the purpose of making compounded versions of Makena®. K-V argues that importation of HPC for use in compounding copies of Makena® is a violation of Section 337 of the Tariff Act of 1930. According to Section 337, “[u]nfair methods of competition and unfair acts in the importation of articles . . . in the United States, or in the sale of such articles by the owner, importer, or consignee, the threat or effect of which is . . . to destroy or substantially injure an industry in the United States,” are “unlawful.” 19 U.S.C. § 1337(a)(1)(A). K-V argues that, because all HPC in the United States comes from abroad, and the only use for HPC is in the manufacture of Makena® or allegedly unlawful copies of Makena®, the importation of HPC undermines federal law and K-V’s statutory orphan drug exclusivity and “is clearly an unfair act and an unfair method of competition.”

According to the Complaint, all the requisites for temporary relief are present. First, there will be immediate and irreparable harm to K-V because the pharmacies compounding copies of Makena® have diverted so much potential revenue from K-V that the drug company has had to file for Chapter 11 bankruptcy. Second, as mentioned above, there is a likelihood of success on the merits. K-V argues that the importation of HPC for the use in compounding violates the prohibition against mass-scale compounding and undermines K-V’s statutory orphan drug exclusivity. These unfair acts and unfair methods of competition are threatening to destroy K-V, i.e., the domestic industry. Third, K-V argues that the following public interest factors favors granting the desired relief: (1) prevention of preterm births; (2) ensuring safe and effective drugs; (3) preservation of a domestic industry; and (4) effectuating Congress’s intent to promote development of treatments for rare conditions. Finally, K-V states that it faces the balance of hardships. K-V argues that the compounding pharmacies have few, if any, protectable rights, whereas K-V has a “Congressionally-granted seven-year exclusive right to market Makena.” Additionally, K-V notes that its business’s survival depends on the success of Makena®, whereas the proposed respondents compound many other products and will survive if they are unable to compound Makena® during the exclusivity period.
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Thumbnail image for Thumbnail image for Thumbnail image for federalcircuit.jpgA panel of three federal circuit judges, Judges Newman, Plager, and Wallach, upheld a decision of the Board of Patent Appeals and Interferences (“Board”) in an inter partes reexamination rejecting certain claims of U.S. Patent No. 6,721,178, owned by Flo Healthcare Solutions, LLC (“Flo”), in an opinion decided on October 23, 2012. U.S. Patent No. 6,721,178 claims a mobile computer workstation for the medical profession.

While the judges disagreed with the reasoning of the Board, the conclusion by the Board was upheld. Judge Plager wrote in the opinion that “the Board erred in holding that the ‘height adjustment mechanism’ limitation of the claims invokes 35 U.S.C. § 112, ¶ 6” because the term “means” was not recited in the claims and the limitation contains a term that designates structure. However, the Board correctly held that “the claims do not require a length-adjustable vertical beam” since the claims do not recite such a limitation even though Flo had the opportunity to amend the claims to include this limitation. Thus, the panel agreed that “the prior art rejections must stand in the absence of such a limitation.”

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Written by Shelly Fujikawa, Ph.D.

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Notably, Judge Plager and Judge Newman both wrote additional views to this opinion urging the en banc review of the standard used by the Federal Circuit when reviewing claim construction decisions by the Board. Both judges were concerned that the Federal Circuit had announced conflicting standards for reviewing such claim constructions. This review would provide a clear standard for the PTO and inventors urged the judges.


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Thumbnail image for Thumbnail image for Supreme Court.jpgOn October 12, 2012, W.L. Gore & Associates Inc. (“Gore”) filed a petition for writ of certiorari with the U.S. Supreme Court, asking the High Court to review the Federal Circuit’s denial of joint-inventor status to one of Gore’s engineers. The patent-in-suit, U.S. Patent No. 6,436,135 (“the ‘135 patent”) lists Dr. David Goldfarb (“Goldfarb”) as the sole inventor (Bard is the assignee.), and Gore argues that Peter Cooper (“Cooper”), head of Gore’s vascular prosthetic research program, should be listed as a joint inventor. Gore alleges that the Federal Circuit erred in setting forth a new standard for joint inventorship that directly conflicts with legislative intent and the plain text of the Patent Act.

In the district court, the jury held that Gore willfully infringed Bard’s patent, and the judge doubled the jury’s damage award, granting $371 million to Bard. The Federal Circuit affirmed the district court’s decision in February 2012, and Gore filed a combined petition for panel rehearing and rehearing en banc. In June 2012, the Federal Circuit granted the motion for rehearing en banc, “for the limited purpose of authorizing the panel to revise the portion of its opinion addressing willfulness.” Gore then filed the instant petition.

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Written by Julie E. Kurzrok

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In the petition, Gore alleges that in 1971, it began a research program focused on the use of stretched Teflon® (“Gore-Tex®”) in vascular prosthetics, or artificial blood vessels. Gore created implantable vessels with varying features, and hired doctors to implant the vessels and to report which ones were successful. Cooper then started an additional experiment involving the porousity of the tubes. Cooper sent small, medium, and large-pore tubes to the physicians, and the results showed that the large-pore tubes (which had a greater “internodal” distance” or “fibril length”) were the winners. Based on this, Cooper conceived of the instant invention on May 1, 1973.
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energy drinks.pngAdverse event reports submitted voluntarily by doctors and companies recently released by FDA state that the deaths of five people over the past three years may have been linked to drinking Monster Energy, an energy drink containing high levels of caffeine. The reports filed using the Center for Food Safety Adverse Event Reporting System spanned a period from 2004 to June 2012, but all of the deaths occurred in 2009 or later. An FDA spokesperson, Shelly Burgess, stated that energy drink manufacturers are responsible for investigating these accusations and that the FDA is investigating these cases, but has not established a causal link between the deaths and the drinks.

The reports were released through the Freedom of Information Act (“FOIA”) to the mother of a 14-year-old girl who recently died after drinking two 24-oz. Monster Energy drinks in a 24 hours period. The parents of the girl have recently brought survival and wrongful death actions against Monster Beverage Corporation (“Monster Beverage”), the manufacturer of Monster Energy, in the Superior Court of the State of California for the County of Riverside using these reports. According to the complaint filed on October 17, 2012, the two 24-oz cans of Monster Energy consumed by the girl contained 480 milligrams of caffeine or the equivalent amount of caffeine in fourteen 12-oz. cans of Coca-Cola. The girl’s autopsy and death certificate state the cause of death as “cardiac arrhythmia due to caffeine toxicity complicating mitral valve regurgitation in the setting of Ehlers-Danlos syndrome” according to the complaint. Ehlers-Danlos syndrome can affect the body’s connective tissue, including blood vessels.

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Written by Shelly Fujikawa, Ph.D.

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The complaint further asserts that, in addition to caffeine, Monster Energy drinks contain guarana and taurine. Guarana contains caffeine and taurine effects cardiac muscles in a similar way compared to caffeine. Caffeine, guarana, and taurine have also been shown to work synergistically. The complaint also alleges that Monster Beverage “avoided meaningful regulation of its products” by FDA since it classified its drink as a “dietary supplement.” Monster Beverage has denied these allegations responding that “Monster is unaware of any fatality anywhere that has been caused by its drinks.”
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onlinepharmacy.jpgPurchasing of pharmaceuticals through on-line pharmacies is on the rise and gives rise to many potential problems. Crucially the most important issue is whether the medicinal product is genuine, contains the correct ingredients, and is an approved product in the relevant regulatory jurisdiction. Medicines supplied via on-line links can come from anywhere in the world, and this method of distribution is more open to fraudulent activity.

In Europe, the European Parliament passed Directive 2011/62/EU, which relates to medicinal products for human use, and is in regard to the prevention of the entry into the legal supply chain of falsified medicinal products. The European Commission (“EC”) has put some thought into how on-line pharmaceutical purchases can be made safe and to comply with the Directive. To that end, they have released a Concept Paper for public consultation on the introduction of a “common logo” for websites of legally-operating on-line pharmacies/retailers.

The requirements are that the logo is recognizable throughout the EU and identifies the Member State in which the on-line pharmacy/retailer is established. There is also an obligation for each Member State to set up a dedicated website providing a national list of all legally-operating on-line pharmacies/retailers. The entries in these lists must have a hyperlink to the respective on-line pharmacies/retailer’s website and a reciprocal link from the logo on the on-line pharmacies/retailer’s website back to the national list. The point being that a customer can go to either the national list to find approvable pharmacies and vice versa to the on-line pharmacies/retailer’s website and link back to the national list via the logo thus assuring authenticity.
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