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  • Conference & CLE Calendar

    CalendarOctober 15, 2014 – European biotech patent law update (D Young & Co will be offering its next) – 4:00 am, 7:00 am, and 12:00 pm (ET)

    October 16, 2014 – "Patent Licensing: Advanced Tactics for Licensees Post-AIA — Structuring Contractual Protections and Responding When Licensed Patents Are Challenged in Post-Grant Proceedings" (Strafford) – 1:00 to 2:30 pm (EDT)

    October 17, 2014 – "Claim Construction Deference: Teva v. Sandoz at the U.S. Supreme Court" (Intellectual Property Owners Association) – 2:00 to 3:00 pm (ET)

    October 21, 2014 – "Recent Judicial Decisions Impacting Technology Licensing" (McDonnell Boehnen Hulbert & Berghoff LLP) – 10:00 to 11:15 am (CT)

    October 21, 2014 – "Patent Reissue: Strategic Use for Pre- and Post-AIA — Correcting Errors in Patents, Determining Whether and When to Pursue a Reissue Application, and Mastering the Recapture Rule" (Strafford) – 1:00 to 2:30 pm (EDT)

    October 21, 2014 – "America Invents Act: Patent Strategies and Reforms Counsel Needs to Know" (Commercial Law WebAdvisor) – 1:00 to 2:30 pm (Eastern)

    October 20-22, 2014 – Business of Biosimilars (Institute for International Research) – Boston, MA

    October 23, 2014 – "Making Sense of New Patent Litigation Alternatives" (ShareVault) – 11:00 am to 12:00 pm (Pacific Daylight Time)

    October 29, 2014 – "Demonstrating Patent Eligibility Post-Alice Corp. Decision — Navigating the Nuances and Leveraging Guidance From Federal Circuit and PTAB Opinions" (Strafford) – 1:00 to 2:30 pm (EDT)

    October 29-30, 2014 - Congress on PIV Litigation (Momentum) – Philadelphia, PA

    November 10-12, 2014 – 2014 Fall Intellectual Property Counsels Committee (IPCC) Conference (Biotechnology Industry Organization) – Nashville, TN

    ***Patent Docs is a media partner of this conference or CLE

  • 2014 BIO IPCC Fall Conference

    Biotechnology Industry Organization (BIO)The Biotechnology Industry Organization (BIO) will be holding its 2014 Fall Intellectual Property Counsels Committee (IPCC) Conference on November 10-12, 2014 in Nashville, TN.

    The conference will offer presentations on the following topics:

    Monday, November 10:

    • Pre-Conference Workshop: Biosimilars Strategy Update

    Tuesday, November 11:

    Session 1: Protecting Products of Nature

    Session 2: Hot Topics:  Safe Harbor, Manufacturing Patents and Patent Term Extension Pitfalls

    Session 3: An Update on ANVISA's Examination of Patent Applications in Brazil and the Status of the Unified Patent Court in Europe

    Session 4: The Evolving Landscape of Litigating Joint and Indirect Infringement

    Wednesday, November 12:

    Session 5: Double Patenting – Double Trouble

    Session 6: Update on Post Grant Review and Inter Partes Review

    In addition, there will be a welcome reception at the Wildhorse Saloon from 5:30 pm to 7:30 pm on November 10, and a dinner reception (sponsored by McDonnell Boehnen Hulbert & Berghoff LLP) at The Country Music Hall of Fame from 5:30 pm to 8:30 pm on November 11.

    A program agenda for this conference, including a list of speakers and descriptions of the presentations and events can be obtained here.

    Registration information can be found here.  Additional information regarding the conference can be found at the conference website.

    BIO IPCC

  • IPO Webinar on Teva v. Sandoz

    IPO #2The Intellectual Property Owners Association (IPO) will offer a one-hour webinar entitled "Claim Construction Deference: Teva v. Sandoz at the U.S. Supreme Court" on October 17, 2014 beginning at 2:00 pm (ET).  Paul Berghoff of McDonnell Boehnen Hulbert & Berghoff LLP, Adam Conrad of King & Spalding, and Peter Menell of the University of California at Berkeley School of Law will review and analyze the oral argument in Teva v. Sandoz, and use the questioning of the justices to give predictions on where the Court may head.

    The registration fee for the webinar is $130 (government and academic rates are available upon request).  Those interested in registering for the webinar can do so here.

  • Webinar on Patent Eligibility Post-Alice Corp.

    Strafford #1Strafford will be offering a webinar/teleconference entitled "Demonstrating Patent Eligibility Post- Alice Corp. Decision — Navigating the Nuances and Leveraging Guidance From Federal Circuit and PTAB Opinions" on October 29, 2014 from 1:00 to 2:30 pm (EDT).  Michael L. Kiklis and Stephen G. Kunin of Oblon Spivak McClelland Maier & Neustadt will examine recent decisions applying the Supreme Court’s decision in Alice Corp. v. CLS Bank on patent eligibility, and discuss the guidance from these opinions and offer best practices for addressing patent eligibility issues.  The webinar will review the following questions:

    • How are the courts applying the framework for patent eligibility created in Alice Corp.?
    • How can patent litigation defendants take advantage of the guidance for Section 101 challenges?
    • What are best practices for patent counsel to demonstrate patent eligibility?

    The registration fee for the webinar is $297 ($362 for registration and CLE processing).  Those interested in registering for the webinar, can do so here.

  • Webinar on Patent Litigation Alternatives

    ShareVaultShareVault will offer a one-hour webinar entitled "Making Sense of New Patent Litigation Alternatives" on October 23, 2014 beginning at 11:00 am to 12:00 pm (Pacific Daylight Time).  John Resek, Ph.D. of Resek Liang & Frank LLC will compare and contrast the two new proceedings for patent litigation created by the America Invents Act, Inter Partes Review (IPR) and Post-Grant Review (PGR), to provide an understanding of how they affect patent owners as well as patent challengers.  The webinar will address the following questions:

    • How can a patent owner protect their patent estate?
    • What is the advantage to the patent challenger of a post grant proceeding?
    • What important strategic issues should be considered?

    Those interested in registering for the webinar can do so here.

  • Webinar on America Invents Act

    Commercial Law WebAdvisor
    Commercial Law WebAdvisor will be offering a webinar entitled "America Invents Act: Patent Strategies and Reforms Counsel Needs to Know" on October 21, 2014 from 1:00 to 2:30 pm (Eastern).  Aaron D. Charfoos of Dykema Gossett PLLC will examine the changes to the patent system introduced by the AIA, as well as strategies in-house counsel and other attorneys advising businesses can employ to put themselves at an advantage when applying for and challenging patents.  The webinar will address the following topics:

    • How the America Invents Act altered the landscape of obtaining and challenging patents,
    • How the change from a “first-to-invent” to a “first-to-file” system affects how patents are awarded,
    • Steps counsel and businesses need to take to secure the earliest possible filing date,
    • New ways to challenge patents after they issue, specifically Inter Partes Review (IPR) and Covered Business Method Review (CBMR),
    • Procedural benefits to IPR and CBMR compared to civil proceedings, and
    • Other litigation assessment strategies.

    The registration fee for the webinar is $299.  Those interested in registering for the webinar, can do so here.

  • Teva v. Sandoz — Supreme Court Preview

    By Andrew Williams —

    Supreme Court Building #1Next week, the Supreme Court will hear oral arguments in the Teva Pharmaceuticals USA, Inc. v. Sandoz Inc. case to determine whether appellate courts should afford any deference to a trial court's claim construction determination.  Specifically, the question presented was phrased as:

        Rule 52(a) of the Federal Rules of Civil Procedure provides that in matters tried to district court, the court's "[f]indings of fact . . . must not be set aside unless clearly erroneous."

        The question presented is as follows:

        Whether a district court's factual finding in support of its construction of a patent claim term may be reviewed de novo, as the Federal Circuit requires (and as the panel explicitly did in this case), or only for clear error, as Rule 52(a) requires.

    The phrasing of the question appears to suggest the answer.  Nevertheless, instead of arguing whether Rule 52(a) applies to findings of fact in claim construction hearings, the parties instead disagreed as to whether claim construction even involves factual issues that would implicate Rule 52(a).  We have recently outlined the procedural background of this case, as well as reviewed the prior Supreme Court and Federal Circuit case law relevant to this issue (see "Supreme Court Preview — Teva Pharmaceuticals USA, Inc. v. Sandoz Inc. — The End of Cybor Corp.?").  This post will preview the position of the parties, as detailed in their briefings to the Court.

    Teva's Brief

    Teva #1Teva, not surprising, portrays claim construction as an endeavor that requires a great amount of fact finding.  "A court often cannot interpret a patent without first understanding what skilled people in the relevant art knew, and what words they used, when the patent application was filed."  Teva's Brief at 15.  As such, Teva argued, the Federal Circuit was incorrect to hold "that every aspect of claim construction, even 'allegedly fact-based questions' [are] reviewed de novo."  Id. at 18 (citing Cybor Corp).  In other words, "[t]he Federal Circuit cannot dodge [Rule 52(a)] by calling a factual question a legal one."  Id.

    In making this argument, Teva explained that patents are written for the intended audience of "persons skilled in the art."  As such, they must be interpreted from that perspective.  Therefore, Teva explained, Courts are required to consult evidence to determine if there is some specialized meaning in the art.  Courts also must look to extrinsic evidence, especially "when the relevant term does not have a single, well-established meaning."  Id. at 28.  Teva also pointed out that expert testimony is often used to elucidate the prosecution history.  Finally, as was the case here, when the validity of the patent is challenged under 35 U.S.C. § 112 ¶ 2, "the dominant inquiry will be a factual one turning on a skilled artisan's knowledge."  Id. at 29.

    The Federal Circuit's appellate review rules for claim construction as compared to other patent validity issues can result in the same evidence being reviewed under two different standards, Teva alleged.  For example, for an obviousness inquiry, the "scope and content" of the prior art is a factual determination.  Nevertheless, if the same prior art is reviewed in the claim construction context, it is treated as a legal matter.  This is also true for the level of ordinary skill in the art.  Teva pointed out that other validity issues are also reviewed deferentially, such as whether a specification enables a skilled artisan to practice an invention.  This same review of the intrinsic evidence is reviewed de novo during claim construction.

    Teva explained why the rationales provided by the Federal Circuit in Cybor Corp, and to a lesser extent Lighting Ballest, are unpersuasive.  First, the conclusion in Cybor Corp did not flow directly from the Supreme Court's Markman decision, Teva argued.  Markman allegedly only resolved who should be performing claim construction, the courts.  However, in so doing, it referenced the factual nature of claim construction several times, whether as a "mongrel practice," a "mixed question of fact and law," or a determination with "evidentiary underpinnings."  The excuse that patents are written instruments, and therefore their interpretation is not entitled to deference, was equally unpersuasive to Teva.  Finally, Teva pointed out that facts cannot be turned into law for the mere sake of uniformity.

    Instead, the brief continued, when the appellate court resorts to its own fact finding, the cost to the patent system is great.  District court judges often provide little to no reasoning for their claim construction determinations, because with de novo review, the Federal Circuit is likely to ignore it anyway.  Appellate courts also do not have the time for a deep review of the science and technology involved, the argument continued.  More importantly, with de novo review, the parties are encouraged to keep litigating, because any adverse decision for claim construction could possibly be ultimately overturned.  Teva was also not persuaded by the proclamation by some Federal Circuit judges of informal deference.  Teva concluded by pointing out that if the Court adopted the "correct" standard, this present case would have come out differently — it would have won.

    Sandoz's Brief

    Sandoz #1Perhaps in response to the wording of the question presented, Sandoz took the position that Rule 52 does not apply to claim construction, which is a "purely legal" question.  Citing Miller v. Fenton, 474 U.S. 104 (1985), Sandoz explained that the "law/fact inquiry turns on whether a judicial actor reviewing the legal standards and the record is more likely to arrive at the correct conclusion, or whether the initial factfinder is better positioned to do so because the credibility of witnesses is pivotal to the issue at hand."  Sandoz Brief at 17.  Because claim construction turns on the claims, specification, and prosecution history, and not the credibility of witnesses, Sandoz continued, any facts that are encountered are merely "legislative facts," and therefore no deference is owed.

    Sandoz explained why de novo review followed directly from Markman.  First, the question presented in that case was "whether claim construction 'is a matter of law reserved entirely for the court, or subject to a Seventh Amendment guarantee . . . .'"  Id. at 19 (citing Markman).  Sandoz did not explain, however, why this legal determination could not be based on underlying factual underpinnings.  Nevertheless, Sandoz argued that the Supreme Court's observations regard the "evidentiary underpinnings" of claim construction actually bolsters the application of de novo review, because that Court concluded that the question is "purely legal".

    The question of uniformity was also addressed.  First, Sandoz explained that uniformity was not a "free-standing principle."  Rather, because patents are federally granted rights, the claim terms should only have one meaning.  Sandoz also responded to argument that issue preclusion could accomplish the same goals of uniformity.  It explained that issue preclusion could not be applied against new alleged infringers.  Instead, by applying stare decisis, the legal precedent of a claim construction decision could not be relitigated, which would promote the "public-notice function of patent claims."  Id. at 40.

    Finally, Sandoz argued that even if the Supreme Court concludes that some deference is required, the outcome of this case would be the same.  It pointed out that Teva did not dispute that the claims are ambiguous on their face.  It was also undisputed that "average molecular weight" has no ordinary and customary meaning, and that it is critical to know which measure is intended.  Importantly, according to Sandoz, the Federal Circuit did not overturn any facts in finding that the claims were indefinite.  Instead, that court determined as a matter of law that statements in the prosecution history were irreconcilable, which resulted in claims that were ambiguous.  Thus, the outcome will be the same according to Sandoz, regardless of which standard this Court articulates.

    We will continue our review of this case next week by highlighting some of the positions found in the amicus briefs.  And, of course, we will provide an update of the oral hearing after the morning of October 15, depending of course on when the transcript is posted to the Supreme Court's web page.

  • Amgen Poised to Enter Biosimilars Market

    By Kevin E. Noonan —

    AmgenAs reported in Fierce Biotech earlier today, Amgen announced the results of a Phase III clinical trial of its biosimilar drug (designated ABP 501) for moderate-to-sever plaque psoriasis conducted in comparison with adalimumab (sold by AbbVie as Humira®).  Amgen's press release asserted that the study, aimed at assessing safety and efficacy of Amgen's biosimilar, "met its primary endpoint" compared with Humira®, where that primary endpoint was evaluated by the Psoriasis Area and Severity Index (PASI).  The result showed improvement "within the prespecified equivalence margin for ABP 501 compared to adalimumab" and that safety and efficacy of Amgen's drug were comparable to AbbVie's drug.

    Adalimumab is a human antibody that recognizes tumor necrosis factor-alpha (TNF-α) developed by collaboration between BASF and Cambridge Antibody Technologies and first approved as a treatment for rheumatoid arthritis (RA) on December 31, 2002.  The drug has been approved thereafter for additional indications, including psoriatic arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, psoriasis and juvenile idiopathic arthritis.  The drug costs an estimated $1,662 per month and had 2012 sales of $4.3 billion in the U.S. and $9.3 billion worldwide.

    The drug is protected by at least U.S. Patent No. 6,090,923, which was granted on July 18, 2000 on an application filed in 1991; the patent will thus expire on July 18, 2017.  Under the provisions of the BPCIA (that portion of the omnibus healthcare reform act commonly called "Obamacare"), AbbVie's market exclusivity expires at the end of this year.  There is no indication that Amgen has filed an application for biosimilar approval under 42 U.S.C. § 262(k) nor that it will file such an application prior to expiry of AbbVie's market exclusivity.  Accordingly, there will be no opportunity for AbbVie to invoke the patent litigation provisions of the Act, unless of course the company has other patents it can identify according to these litigation provisions.

    This scenario follows closely the scenario forecast by the Federal Trade Commission during debate over the provisions of the Act; the FTC predicted that, unlike "traditional" generic drug companies it would be more established, conventionally innovator and branded biologic drug companies that would enter the biosimilars market.  The FTC also predicted that reductions in biologic drug costs would be in the range of 20-30% of the innovator biologic drug costs which, while a significant savings is much less than the experience with small molecule generic drugs.  It also remains to be seen whether Amgen's drug, or any other biosimilar drug will be able to satisfy the as yet unenunciated standards for interchangeability, which would make any such biosimilar drug much more attractive in the marketplace.

  • Guest Post: Nature’s Indelible Marker

    Naturally abundant, stable isotopes have already protected the identity and origin of $1.5 billion in pharmaceutical materials against Intellectual property infringers

    By Anthony D. Sabatelli* —

    The pharmaceutical industry is an important segment of the world economy.  In 2013, worldwide sales of prescription drugs were over $830 billion.  If one adds in over-the-counter medicines and other health-related products such as vitamins and nutritional supplements, that market approaches nearly $1 trillion dollars annually.  With such huge markets at stake, there is the continuous threat of unauthorized sales of competing counterfeit and patent-infringing pharmaceutical products.

    In an effort to find a simple, accurate way to unequivocally identify and secure the origins of drugs and other compounds, a Niantic, Connecticut-area scientist developed an alternative, finding a way to use the naturally occurring molecular fingerprint of drug products, active pharmaceutical ingredients and their synthetic pathways to help biotech and pharmaceutical companies enforce their hard-won patent rights against counterfeiters and other bad actors looking to profit by stealing intellectual property.

    According to Dr. John Jasper, chief scientific officer for Nature's Fingerprint, a division of Molecular Isotope Technologies LLC (MIT LLC), this fingerprinting technology has real, practical, application potential.  "What we are doing is measuring chemical tracers, also known as stable isotopes, to determine the origins of drug products and pathways to help pharmaceutical companies and law enforcement authorities combat Intellectual property infringement," says Jasper.  "The distribution of natural-abundance stable isotopes in a drug product is analogous to the highly specific pattern of a human fingerprint.  It is this 'fingerprint' of nature that can be used to highly specifically identify the source or process for a given drug product."

    THE HISTORY OF ISOTOPES

    Jasper explains that large-scale scientific research involving both radioactive and non-radioactive (i.e., stable) isotopes goes back to the time of the Manhattan Project, which produced the first atomic bombs during World War II. Isotopes — whether stable or radioactive — are forms of the same chemical element having different atomic masses.  For example, uranium has an isotopic form with a mass of 235 and also an isotopic form with a mass of 238.  By 1942, isotopes had only been known for about 30 years.  Most of the research involving isotopes had been theoretical, relating to determining atomic structures and studying the then-mysterious properties of radioactivity.  The Manhattan Project changed all that.  The dire urgency of the war effort led to the development of sophisticated techniques for separating and identifying isotopes.  One of these techniques, Isotope Ratio Mass Spectrometry (or IRMS for short), which is used to measure the relative abundance of isotopes in a sample, is now an important methodology in the field of those studying and using isotopes.

    HIGHLY SPECIFIC FINGERPRINT

    In 1999, Jasper began developing the technology around the premise that naturally abundant, stable isotopes might be used to identify individual batches of pharmaceutical materials.  According to Jasper, "we had shown that every batch of pharmaceutical products had its own highly specific 'isotopic fingerprint.'  We subsequently realized the potential applications of our technology to provide evidentiary support for patent infringement and enforcement efforts had just opened up immensely."

    TWO U.S. PATENTS

    The technology is sufficiently unique that it was awarded two U.S. patents, the most recent being issued in 2013.  The latest patent relates to methods and systems to correlate a product such as a pharmaceutical to the synthetic process by which it was made.  In other words, the method is a means of finding the "smoking gun" of the patent infringer.  Even the FBI has recognized the value of this unique technology, calling upon Jasper for advice during the anthrax scare post 9/11.

    ADDING VALUE

    It is well recognized that pharmaceutical research is a high-risk and expensive undertaking.  It takes many years and huge investments to bring a new drug product to the marketplace.  This is not surprising considering that a single human Phase III clinical trial can easily top $50 million dollars to run.  Phase III is the last stage of clinical testing before a pharmaceutical developer submits an application for drug approval to the FDA.  The FDA typically requires two such "well-controlled" studies for drug approval.  According to the Tufts Center for the Study of Drug Development, which has been tracking the cost of prescription drug development for over 30 years, the cost of developing a single new drug today is estimated to cost as much as $1.2 billion.  On top of this immense cost, the average time for bringing a new drug to market from its original inception in the lab is now over 10 years.  Finally, the success rate for prescription drug development is quite low — by some estimates, only about one in 20 drugs make it all the way from initial Phase I human clinical trials to the marketplace. Going back even further to inception at the lab bench, the success rate might be just one in several thousand.

    Figure 1
    The main way to secure protection for new pharmaceutical products is through sound patent protection.  However, the cost of patent protection is high and time consuming.  The "gold standard" in patent protection for a new, small organic molecule drug product is a composition of matter patent.  Such patents specifically describe or "claim" the drug compound, and preferably a broader genus of chemical structures surrounding that compound.  Furthermore, the cost for filing, obtaining and maintaining a single patent across a broad range of countries can cost tens of thousands of dollars, and in many instances can easily top a half a million dollars.

    However, it is not always possible to obtain a "composition of matter" patent.  In other instances, because of long drug development timelines and stringent regulatory requirements and review, a significant amount of the patent term (typically 20 years) of the composition of matter patent has already ticked away by the time the product has been approved for marketing.  Even though the U.S. Patent Office, in conjunction with the FDA, provides for up to five years of patent term restoration, the restored patent term can still be relatively short.  In many cases, composition of matter patents may have expired or may not otherwise be available for reasons having nothing to do with the soundness, value or utility of the underlying drug product.

    Whether or not there is a composition of matter patent, pharmaceutical companies often supplement their patent portfolios with patents covering manufacturing processes and improvements (i.e., process patents).  These patents are sometimes referred to as secondary patents.  These patents can relate to more efficient processes or products with improved purity profiles or properties.  However, these secondary patents can be more difficult to monitor and subsequently enforce.  The reason for this is that the evidence necessary to substantiate a claim of infringement is not as easy to obtain or demonstrate as in the case of a composition of matter patent.

    Counterfeiting of pharma products and infringement of patent processes are multi-billion-dollar problems for the pharmaceutical industry.  Here is where the technology developed by Dr. Jasper can potentially be successful.  Figure 1 graphically illustrates the period of additional patent protection potentially afforded by the use of MIT LLC's stable-isotopic approach to process patent protection.

    IDENTIFYING DRUG SOURCES

    How can isotopic fingerprinting technology differentiate the source of a drug and/or the process by which it is made?  "All chemical compounds have highly specific ratios of natural stable isotopes," explains Jasper.  Thus every batch of a pharmaceutical material has its own highly specific isotopic fingerprint.  The method can be used to identify, track and classify batches of products.  The technology can identify not only the type of chemical processes used in making a drug, but also the identifying information of the specific manufacturing site as well."

    Figure 2
    VERY SENSITIVE

    This fingerprinting technology provides a means to investigate and determine facts, facts that can prove provenance and process.  Many times it is difficult to monitor and enforce process patents because of the difficulty of finding persuasive evidence of infringement.  The reason isotopic evidence can be so persuasive is because it is so sensitive.  The technology can measure very small differences in natural isotopic ratios between samples.  Because of this sensitivity the method can, with a very high degree of certainty, determine whether two or more samples or processes are the same or different.  According to Jasper, "we can perform very highly precise analyses on samples that are only a fraction of a milligram."  (To put this in perspective, a typical grain of salt weighs less than a milligram.)

    In 2005, in a blind study commissioned by the FDA, MIT LLC characterized 26 batches of the pain reliever, naproxen, to determine the product fingerprint or source characteristics for the batches.  The FDA wanted to assess the robustness of the fingerprinting method for determining the manufacturing sites for pharmaceutical products.  If the method could provide this source information, it would be an important investigative and forensic tool for drug enforcement authorities trying to determine the provenance of a product.  For this study, Jasper and his team determined the ratios of the naturally occurring carbon and oxygen isotopes for each of the naproxen batches. It turns out Jasper and his team had correctly determined that the batches had come from six different manufacturing sites from around the world (See Figure 2).

    Figure 3
    POTENTIAL APPLICATIONS

    To date, Jasper's technology has been employed in three lawsuits, with two lawsuits being decided in favor of plaintiffs claiming patent infringement against counterfeiters.  Further, his technology also helped another defendant ward off an unfounded patent infringement claim.  MIT LLC conducted a study for this defendant comparing the naturally occurring carbon-isotope ratios for the defendant's products versus the ratios for a product made by the plaintiff's patented process.  The data unequivocally showed that the defendant's product could not have been made by the patented process as alleged by the plaintiff.  Based on the data, the defendant was found not guilty of patent infringement and they were free to bring their product into a major, new international market (See Figure 3).

    These results highlight the potential impact of this fingerprinting technology, particularly to adding value to a company's patent estate.  A conservative estimate puts the value of the products protected by the technology at more than $1.5 billion in total sales over the time the settlements were in effect.

    MORE INNOVATION COMING

    What's next for Jasper's innovative identity tool?  Jasper says MIT LLC continues to expand its business development outreach while working to develop new isotope analysis tools.  For example, Nature's Fingerprint has developed new technology to evaluate naturally occurring isotopes in high molecular weight molecules and complex biological systems.  Recent studies, says Jasper, have demonstrated the successful application of the technology to biologic compounds in the 8,000 to 15,000 dalton molecular-weight range (Jasper, et al., J. Pharm. Sci. 2014, in press).  Such high molecular-weight compounds can be more than two orders of magnitude larger than the typical low-molecular weight drug compounds.  For comparison, naproxen has a molecular weight of 230.  Jasper pointed out that in principle, there is really no upper limit to the size molecules or systems to which his technique can be applied, but rather it is ancillary issues such as sample preparation and purification that may present some challenge.

    Figure 4
    Additionally, the company has developed technology for continuously monitoring the progress of chemical and biological reaction processes.  This technology is based on the partitioning of natural-abundance stable isotopes between the reactants and products of a chemical or biological process through the course of a reaction.  The technique can have a wide range of applications from monitoring the progress of a chemical reaction in a pilot plant to the large-scale production of commodity chemicals.  In theory, the isotopic composition of a reaction product can be plotted as a function of reaction yield.  For example, there is good reason to believe that the stable-isotopic composition of reaction products should be proportional to the instantaneous yield of the reaction.  That is, the isotopic composition (δ) should increase as the reaction yield for the process approaches completion (i.e., 1.0).  The symbol, ‰, designates per mil (a/k/a parts per thousand).  Jasper says he is positive about this development because it applies the isotope technology to solving real-time monitoring problems for process chemistry and other manufacturing processes (See Figure 4).

    Things have come a long way from the early 1900s when researchers first postulated the existence of different isotopic forms of the chemical elements.  Nature's Fingerprint has found a unique application of this isotope technology.  It is a company to watch, particularly as it continues to add value to and protect the pharma industry's intellectual property.

    * Dr. Sabatelli is a Partner with Dilworth IP.

    This article was originally published on September 3, 2014 on PharmaManufacturing.com.

  • Guest Post: Will Purple Become The New Orange? FDA Publishes Long-Awaited Lists Governing Biologics

    By Anthony Sabatelli* —

    FDA Purple BookSome fashion trends may come and go, but in the not too distant future the majority of prescription drug sales will be purple.1 For those of you not yet familiar with this latest trend, allow me to explain.

    Most drug products are small, synthetically produced substances.  The common pain reliever ibuprofen, for example, contains only 33 atoms and has a molecular weight of 206.  In contrast, there is a whole new class of complex drug products that are isolated or produced from biological sources such as living cells.  These biologically produced drugs, more commonly called "biologics," are orders of magnitude larger than their small molecule cousins and present special challenges in their preparation, isolation, and administration. Insulin is a common example of a biologic.  It is a protein having a molecular weight of approximately 5800.  Another example is the hormone erythropoietin (or "EPO"), which is used to treat anemia.  EPO is a far larger biological drug with a molecular weight of nearly 35,000.

    So what does this have to do with the color purple?

    First, Enter The Orange Book

    Small-molecule prescription drugs are approved by the US Food and Drug Administration (FDA).  In 1984, Congress passed the Drug Price Competition and Patent Restoration Act (commonly known as "Hatch-Waxman") to bring low-cost prescription drug products to consumers, while balancing the competing interests of the branded pharmaceutical industry and generic drug manufacturers.  Hatch-Waxman provided a unique statutory link between the patent and regulatory systems and established a framework under which generic drugs could be marketed.  Hatch-Waxman requires the FDA to publish information on approved drug products with their therapeutic equivalence information.  Also published are patent and other exclusivity information for the approved drugs, setting the grounds for the complex litigation that results when the interests of the branded and generic drug manufacturers clash.  The FDA publication in which this drug and patent information appears is known, not by its lengthy title2, but rather by its distinctive orange cover — hence, the "Orange Book."

    Now Enter the Purple Book

    Fast forward to 2014, or rather first to 2010.  In March of that year, President Obama signed into law the Patient Protection and Affordable Care Act (more commonly known as "Obamacare").  One of the Act's provisions was the Biologics Price Competition and Innovation Act ("BPCIA"), which created an abbreviated licensure pathway for biologics that are demonstrated to be either "biosimilar" to or "interchangeable" with the originally approved product.3  In other words, the legislation created a regulatory pathway for the approval and marketing of the generic equivalent of a biological drug.  This regulatory pathway is just getting off the ground.  Even though biologics have been around for a long time (synthetic insulin was marketed in 1982), no biosimilar product has as yet been approved in the United States.  In fact, it is believed that only two biosimilar applications are currently pending before the FDA.  However, this will all soon change and the first biosimilars are expected to receive approval in 2015.

    Since the passing of the BPCIA, the FDA has issued various announcements on biologics and biosimilars, including a long-awaited Draft Guidance that was published in August.  The big news, however, is that the FDA just published its first edition of the Purple Book, with the lengthy title — "Lists of Licensed Biological Products with Reference Product Exclusivity and Biosimilarity or Interchangeability Evaluations."  This publication, like its Orange Book Counterpart, lists approved biological drug products and will eventually list biosimilar and interchangeable products as they are approved. The published information, however, is still not complete.  For example the date of first licensure and the expiry of product exclusivity are only listed for three products.  Clearly, the FDA has much work ahead to compile complete information.

    Will There Be A Color Clash?

    It will be interesting to see how the Purple Book will function.  Will it clash with the Orange Book?  After all, orange and purple are not exactly complementary colors.  Only time will tell as biologics overtake the pharmaceutical market and the first biosimilar and interchangeable products begin receiving approval.

    __________________________

    [1] As explained in this article, biologically produced drugs ("biologics") will be governed by the US Food and Drug Administration's (FDA's) newly established "Purple Book."  Depending on the source and how the data is analyzed, biologics accounted for just 10 percent of annual prescription drug sales in 2010.  By 2017, that number could well surpass 50 percent.  Notwithstanding the data, the trend is clear that biologics will account for a majority of prescription drug sales.

    [2] Approved Drug Products with Therapeutic Equivalence Evaluations

    [3] "Biosimilars" and "Interchangeables" are two different types of biological generic products.

    * Dr. Sabatelli is a Partner with Dilworth IP.

    For additional information regarding this topci, please see:

    • "FDA Announces 'Purple Book'," September 16, 2014