Sunday, March 02, 2014
Wednesday, October 09, 2013
The Practising Law Institute has very kindly provided Biolaw a copy of its EPA Compliance and Enforcement Answer Book for 2013. Edited by by Adam Sowatzka and Richard E. Glaze, Jr., this volume reviews the full array of laws enforced by the United States Environmental Protection Agency, including federal laws that delegate enforcement authority to the states. The Compliance and Enforcement Answer Book provides practical details on compliance and enforcement — the real work of individuals, firms, and state and local government officials who deal day-to-day with the EPA. PLI's stated goal is to give these actors, and their lawyers, one compact tool for dealing with EPA's vast army of inspectors, investigators, scientists, and lawyers.
Biolaw appreciates PLI's generosity and wishes its readers much success with this environmental law resource.
Wednesday, November 21, 2012
Recently received in the Jurisdynamics Network's mailbox:
At a ceremony announcing the completion of the first draft of the human genome in 2000, President Bill Clinton declared, "I believe one of the great truths to emerge from this triumphant expedition inside the human genome is that in genetic terms, all human beings, regardless of race, are more than 99.9 percent the same." Yet despite this declaration of unity, biomedical research has focused increasingly on mapping that .1 percent of difference, particularly as it relates to race.
This trend is exemplified by the drug BiDil. Approved by the FDA in 2005 as the first drug with a race-specific indication on its label, BiDil was originally touted as a pathbreaking therapy to treat heart failure in black patients and help underserved populations. Upon closer examination, however, Jonathan Kahn reveals a far more complex story. At the most basic level, BiDil became racial through legal maneuvering and commercial pressure as much as through medical understandings of how the drug worked.
Using BiDil as a central case study, Kahn broadly examines the legal and commercial imperatives driving the expanding role of race in biomedicine, even as scientific advances in genomics could render the issue irrelevant. He surveys the distinct politics informing the use of race in medicine and the very real health disparities caused by racism and social injustice that are now being cast as a mere function of genetic difference. Calling for a more reasoned approach to using race in biomedical research and practice, Kahn asks readers to recognize that, just as genetics is a complex field requiring sensitivity and expertise, so too is race, particularly in the field of biomedicine.
Wednesday, October 31, 2012
Patent rights that encumber components and methods have long been a concern among those in synthetic biology, especially as a perceived threat to the field’s prominent ethos of open biological innovation. Currently, there is little evidence that patent rights adversely affect synthetic biological research...In fact, the patent-eligibility of DNA molecules has been put in doubt by several conflicting U.S. court decisions...What is certain is that the synthetic biology community is unusually attuned to debates surrounding intellectual property and standards setting, and views its engagement in these debates as vital to ensure the continued success of synthetic biology.
Anyone interested in learning more about synthetic biology, biotechnology, and intellectual property law is welcome to download free copies of the following articles: (1) Synthesizing Law for Synthetic Biology, (2) Gene Concepts, Gene Talk, and Gene Patents, (3) DNA Copyright, and (4) Planted Obsolescence: Synagriculture and the Law.
For more biolaw, visit LEXVIVO.
Sunday, October 21, 2012
Jim Chen, Bioprospect Theory, available at http://ssrn.com/abstract=2164848 or http://bit.ly/BioprospectTheory. To be presented at the University of Akron School of Law's sixth annual Intellectual Property Scholars Forum.
Conventional wisdom treats biodiversity and biotechnology as rivalrous values. The global south is home to most of earth's vanishing species, while the global north holds the capital and technology needed to develop this natural wealth. The south argues that intellectual property laws enable the industrialized north to commit biopiracy. By contrast, the United States has characterized calls for profit-sharing as a threat to the global life sciences industry. Both sides magnify the dispute, on the apparent consensus that commercial exploitation of genetic resources holds the key to biodiversity conservation.
Both sides of this debate misunderstand the relationship between biodiversity and biotechnology. Both sides have overstated the significance of bioprospecting. It is misleading to frame the issue as whether intellectual property can coexist with the international legal framework for preserving biodiversity. Any lawyer can reconfigure intellectual property to embrace all of the intangible assets at stake, including raw genetic resources, advanced agricultural and pharmaceutical research, and ethnobiological knowledge.
The real challenge lies in directing biodiversity conservation and intellectual property toward appropriate preservation and exploitation of the biosphere. Commercial development aids biodiversity primarily by overcoming perverse economic incentives to consume scarce natural resources that may turn out to have greater global, long-term value. We continue to debate these issues not because we are rational, but precisely because we are not.
Indeed, legal approaches to biodiversity and to biotechnology are so twisted that they represent an extreme application of prospect theory. Losing supposedly hurts worse than winning feels good. The law of biodiversity and biotechnology appears to reverse this presumption. Biodiversity loss is staggering and undeniable. Humans are responsible for the sixth great extinction spasm of the Phanerozoic Eon. By contrast, gains from bioprospecting are highly speculative. Even if they are ever realized, they will be extremely concentrated. There is no defensible basis for treating ethnobiological knowledge as the foundation of a coherent approach to global economic development.
In spite of these realities, the global community continues to spend its extremely small and fragile storehouse of political capital on this contentious corner of international environmental law. Global economic diplomacy should be made of saner stuff. The fact that it is not invites us to treat the entire charade as a distinct branch of behavioral law and economics: bioprospect theory.
Saturday, October 20, 2012
Friday, September 14, 2012
After public debates spanning half a human lifespan, Portland, Oregon, has finally elected to fluoridate its water. Portland's city council has voted unanimously to add fluoride beginning in 2014, at a projected cost of $5 million.
By any strictly scientific calculus of public health costs and benefits, this is an easy and obvious decision. The Centers for Disease Control and Prevention rank fluoridation among the 20th century's ten most significant advances in public health. Citing Brian A. Burt & Steven A. Eklund, Dentistry, Dental Practice, and the Community 204-20 (1999), the CDC has observed:
Fluoridation of drinking water began in 1945 and in 1999 reaches an estimated 144 million persons in the United States. Fluoridation safely and inexpensively benefits both children and adults by effectively preventing tooth decay, regardless of socioeconomic status or access to care. Fluoridation has played an important role in the reductions in tooth decay (40%-70% in children) and of tooth loss in adults (40%-60%).
In an open letter to his constituents, Mayor Sam Adams defended fluoridation on classic, straightforward grounds of social justice. Tooth decay, the mayor wrote, disproportionately afflicts poor and minority populations. Young children are especially vulnerable to tooth decay; those who suffer from it face negative lifelong consequences for their health and for their economic well-being. At $5 million, fluoridation may be Portland's most cost-effective way of delivering a positive dental health benefit to its citizens, especially the most socially vulnerable.
The public backlash in this proudly liberal city will undoubtedly be fierce. Given an opportunity to vote on fluoridation, Portlanders voted "no" in 1980. For all their trouble and their prudent acts on behalf of public health, Mayor Adams and the city council members who finally propelled Portland into the
Saturday, August 04, 2012
Mitt Romney may become our next president. Will he continue to espouse one-factor explanations for multicausal problems, and fail to understand history and the modern world? If so, he will preside over a declining nation squandering its advantages of location and history.One suspects that Romney may not win Diamond's vote come November.
More biolaw at Lexvivo.
Thursday, June 28, 2012
Supporters of GM agriculture have had a long row to hoe in achieving public acceptance for the safety of this important technology. Controversy has surrounded the foundational technology of recombinant DNA methods, the application of genetic engineering to crop plants and livestock, the safety of GM “Frankenfoods” as sources of human and animal nutrition, the potential environmental threats posed by the possible development of GM “superweeds,” and the corporate control over GM agriculture exercised by a relatively small number of agricultural companies armed with vast financial resources and powerful patent portfolios. Nevertheless, as exemplified by the United States and Canadian Supreme Court cases, Diamond v. Chakrabarty, J.E.M. v. Pioneer Hi-Bred, Monsanto Canada v. Schmeiser, and Monsanto v. Geertson, the law, and the society it reflects, have finally managed to accommodate the important technology of GM agriculture. However, a new paradigm in biological science — synthetic biology — has begun to remake the face of GM agriculture. Synthetic biology seeks to purge biology of some of its fundamental inefficiencies through the rigorous application of engineering principles. Rather than tinkering around the edges, biological engineering would remake living organisms from first principles, and employ standard parts to make qualitatively new biological devices and systems. Traditional arguments that GM crops and livestock are simply slightly-modified versions of their conventional counterparts may no longer be either appropriate or accurate in the face of synthetic biological approaches to engineering new plants. Moreover, both synthetic biology and do-it-yourself biology (“DIYbio”) seek to shift biological research and development out of traditional laboratories and the hands of credentialed biologists, and, instead, allow any interested and motivated user to become a research biologist, biotinkerer, or synthetic biological engineer. Home and community laboratories are already springing up at a rapid rate, and farm laboratories are sure to follow, as participation in this new, open, and democratized movement burgeons. In short, large numbers of individual and collaborating users, spread over many small and local laboratories, are beginning fundamentally to reengineer genes, cells, organisms, and systems composed of organisms or their substituent parts. The comfortable acceptance of GMOs at which society has only recently begun to arrive may soon be misplaced in the face of both fundamentally new scientific approaches and the democratization of innovation. The results for agriculture may be beneficial: enhanced rates of agricultural innovation through new biological approaches and wide participation. Moreover, synthetic biological agriculture (“synagriculture”) may prove to be as safe as GM agriculture or even conventional agriculture. However, assumptions about current GM crops and livestock may not easily apply to synthetic versions, nor may the current paradigm of GM regulation be possible when innovation becomes atomized among millions of farmers. Some of the “settled” legal issues surrounding GM crops and livestock may have to be revisited as new perceived or actual threats and benefits arise. One irony may be that the same patent system that has so often been criticized in the past for providing agricultural companies with too much control over farmers may soon represent one of the most effective methods for monitoring and regulating GM agricultural innovation. Although some farmer innovators may eschew patent coverage for their agricultural inventions, others may opt to seek patent protection for their innovative new synthetic crops and livestock. Because the USPTO will have to examine any new GM crop inventions prior to issuing letters patent, disclosures to the USPTO synthetic biological inventors who opt for patent protection may become a vital centralized locus for monitoring and regulating otherwise highly-decentralized synagricultural innovation. New methods of biological engineering and new models of user, collaborative, and open innovation are soon to affect the trajectory of GM agricultural innovation. Even if such changes turn out to be salutary, they will be changes nevertheless. To ensure that society receives the full benefits of open and democratized synthetic biological innovation in crops and livestock, it would be well and wise for the law to prepare itself to reexamine the brave new world of synagriculture with brand new eyes.Henri Alain once wrote that "Life on a farm is a school of patience; you can't hurry the crops or make an ox in two days." Toutes les bonnes choses ont une fin.
Thursday, April 12, 2012
The language of the genes has a simple alphabet, not with twenty-six letters, but just four. These are the four different DNA bases—adenine, guanine, cytosine and thymine (A, G, C and T for short). The bases are arranged in words of three letters such as CGA or TGG. Most of the words code for different amino acids, which themselves are joined together to make proteins, the building blocks of the body.The letters in the alphabet of DNA nucleotide bases can form words that, in turn, can express meaning. Synthetic biology allows works of expressive authorship to be fixed in the tangible medium of DNA expression. Thus, DNA may be eligible for copyright protection, as I argue in a recently-published (and freely-downloadable) article, DNA Copyright. Here is the abstract:
Copyright law has traditionally afforded protection to works of authorship such as books, magazines, photographs, paintings, music, and sculpture. The Copyright Act has proved admirably flexible at accommodating novel categories of authorship, specifically contemplating future developments by covering “original works of authorship fixed in any tangible medium of expression, now known or later developed.” This has led to explicit copyright protection for nontraditional subject matter, such as works of architecture and computer software. Sequences of DNA should also be acknowledged as eligible for copyright protection. Unaltered genomic DNA sequences would seem poor candidates for copyright protection. The case is stronger for copyright protection of recombinant DNA sequences. Strongest is the case for the copyright eligibility of synthetic DNA sequences designed nucleotide by nucleotide and chemically constructed de novo. Whereas DNA copyright has previously remained a largely hypothetical prospect, advances in synthetic biology may now force recognition of copyright protection as an alternative (or complement) to patent protection. A DNA copyright regime would differ substantially from the current DNA patent regime. Notably, acquiring copyright protection for DNA would be less expensive and much more rapid than pursuing patent protection. While patent law recognizes few and weak exceptions to infringement, copyright law offers a robust fair use exception for copying done in contexts such as scholarship and research. Furthermore, copyright protection would be limited in the case of DNA molecules whose structures are dictated by functional constraints, thus providing the public greater and salutary access to useful genes. Copyright protection for DNA lies pregnant within current copyright law. What is required is an effort to make use of this existing protection. A DNA copyright regime would not only allow a more robust set of safe harbors for use of particular DNA sequences, especially in genetic research, it would also facilitate the possibility of an open source biology movement. Finally, just as the prospects of patent protection for at least some forms of DNA have become uncertain, copyright protection could fill any resulting gap by affording a reasonable level of intellectual property protection, while simultaneously allowing society to enjoy some of the benefits of genetic knowledge more freely than patent protection currently allows.In light of its March 20, 2012, decision, Mayo Collaborative Services v. Prometheus Laboratories, Inc. (U.S. 2012) (previously discussed on LEXVIVO) the United States Supreme Court vacated and remanded the July 29, 2011, Court of Appeals for the Federal Circuit ("CAFC") decision, The Association for Molecular Pathology, et al. v. Myriad Genetics, Inc., et al. (also previously discussed on LEXVIVO), that had upheld the patent eligibility of DNA sequences.
Unless the CAFC can safely navigate gene patents past the patent eligibility perils of Scylla (Bilski v. Kappos (U.S. 2009)) and Charybdis (Mayo v. Prometheus), copyright may soon be seen as the best hope for securing intellectual property protection of DNA inventions.
More biolaw is available at LEXVIVO.
Wednesday, March 21, 2012
In vivo conversion is a process, often metabolic in nature, wherein one substance, usually a chemical compound, is altered significantly by physiological pathways in the body into one or more different substances. For example, when a patient ingests a therapeutic drug, that drug is often converted by the natural physiology of the digestive system into one or more chemically different metabolites. The end products of in vivo conversion sometimes possess therapeutic efficacy. Many patent applications have claimed such therapeutic metabolites, either as compositions per se or as parts of methods of treatment. Although the United States Patent and Trademark Office has granted patent claims to such products generated by in vivo conversion of ingested drugs, and courts have noted the eligibility of such products as patentable subject matter, never has a United States court of final appeal upheld such a patent claim as valid, enforceable, and infringed. The unanimity of results in cases involving patent infringement triggered by in vivo conversion is striking. In fact, its very improbability suggests a common underlying explanation for why in vivo conversion does not ever seem to trigger patent infringement. Explanations based on inherency or a lack of evidence provide a satisfactory explanation for only a minority of in vivo cases. The "Physiological Steps Doctrine," which suggests that products and processes of in vivo conversion are unpatentable subject matter under United States patent law, offers an explanation that spans all in vivo conversion cases. Though the rationales offered to explain the results in a number of in vivo conversion cases are suggestive, there are several advantages for a more explicit recognition of the Physiological Steps Doctrine. Consistent with much international, European, and U.S. patent law, the Physiological Steps Doctrine provides a theoretical underpinning to explain the results in cases involving products and processes of in vivo conversion. This theoretical underpinning not only has explanatory power for interpreting previous case law but is also useful in predicting the outcome of future in vivo conversion cases. In addition, the Physiological Steps Doctrine increases the understanding of where inventions involving human beings, and the biological products and processes thereof, fit within the spectrum of patentable subject matter.On March 20, 2012, the United States Supreme Court unanimously confirmed Physiological Steps Doctrine by holding invalid Prometheus Laboratories' patent claims to uses of in vivo conversion products in diagnosis and therapy. The decision, Mayo Collaborative Services v. Prometheus Laboratories, Inc. (U.S. 2012), may not only sound the formal death knell of in vivo conversion patents, but also cast severe doubt on the patent eligibility of wide swaths of the personalized medicine and genomics fields. LEXVIVO has discussed previous chapters in the Prometheus saga by the Supreme Court and the Court of Appeals for the Federal Circuit ("CAFC").
It would now be unsurprising if the Supremes were to vacate and remand the July 29, 2011, CAFC decision in The Association for Molecular Pathology, et al. v. Myriad Genetics, Inc., et al. (previously discussed on LEXVIVO) that upheld the patent eligibility of gene patents. If so, genome-derived DNA patents could be the next domino to fall in the recently turbulent game of patentable subject matter.
More biolaw is available at LEXVIVO.
Thursday, January 12, 2012
Editor's note: This is the third installment of a three-part series.
In Parts 1 and 2, we learned that it is both possible and valuable to import empirical scientific methods typically used in the hard sciences to the study of law. In fact, in our analysis of patent law and policy we can move beyond patent valuation to assess how and indeed whether a given piece of law or policy is working in conjunction to its so-called original policy intent. This includes the assessment of innovation within the context of the patent bargain, and whether governments that have accepted linkage laws are being rewarded in their twin policy goals of producing more new and innovative drugs and facilitating timely generic entry. Put another way, can we assess using the new tools of empirical legal research whether, as Senator Hatch put it at the time the U.S. linkage legislation came into force, the public is in fact “receiving the best of both worlds - cheaper drugs today and better drugs tomorrow.”
We can attempt to address this possibility using the innovation index discussed in Part 2 in combination with 3-D spatiotemporal models such as those used in the medical sciences. Over the last few decades, these models have been used increasingly for studying protein, DNA, RNA, and other structure-function relationships, including using x-ray and other crystallography techniques. Consistent with their use in medicine, 3-D legal models can be used to construct data for both descriptive (structural) and prescriptive (functional) law-making and law-reform purposes.
Read the rest of this post . . . .For example, in our Northwestern study, we developed a 2-D model of identifying patents in relation to “new and innovative” drugs and “follow-on” drugs that tracked the functional and temporal evolution of drug forms and associated patents over time. The example below is for the combination of Salmeterol and Fluticasone into one of several available forms of Advair®. We referred to this technique as a “patent tree” method and used it specifically to identify legally-related drug forms, associated patents, and patent types.
Fig. 1. Example of Convergent Patent Tree Analysis for Forth Generation Product Advair Diskus.®Patents were identified using the specific and general search strings described in our Berkeley study. In addition to quantifying patents per drug, the patent tree method allows assessment of how specific drugs evolve into related drug forms or (in this case) drug products representing combinations of known drugs. In addition, the patent tree analysis allows for identification of relevant patent types based on the classification nomenclature described in the Northwestern study. Finally, the patent tree analysis provides data relating to drug development, but also on the type of patents selected by pharmaceutical companies for listing on the patent register in order to prevent generic entry.This method can be extended, as shown below, to identify “product clusters.” In particular, the patent tree method can easily be expanded to include patents listed on the patent register under linkage law, and a diagonally increasing axis of cumulative spatiotemporal growth. The resulting model represents a constellation of legally and functionally related new and follow-on drug forms and regulatory approvals, patents associated with these drug forms, the fraction of total patents listed on the patent register in order to slow down generic entry under linkage laws, and how each of the data classes relate to one another over time.
Fig. 2 Product Cluster-Based Model of Drug Development.Product clusters begin at some point in time with the first new and innovative drug (●; NCE) and associated originating patent (●). With time, and vetting by the market and regulators, further follow-on drug approvals (●) and patents (●) are granted within the cluster, and an increasing number of these patents are listed on the patent register (●). Listed patents can be used increasingly over time to prohibit generic entry not only on the originating new and innovative drug, but also on all drugs in the cluster that are deemed under law to be relevant to the originating drug.We are now in a position to take our 2-D product cluster model above, first reported in 2011, and combine it with the innovation index depicted in Part 2 of this series, reproduced below for convenience.
Fig. 3. Innovation Index Data for Total Approval Cohort. Bar graphs showing the number of total approvals expressed as a function of the level of innovation (LOI) before (a) and after (b) of generic approval data. c Brand approvals expressed as a function of LOI. Solid line is a fit of the data to a single exponential function. d Cumulative normalized brand approvals expressed as a function of LOI. Solid line is fit using a sigmoidal function.The combination of the drug nomenclature, product cluster and innovation index described in Fig. 4 yields a potentially new way of looking at the impact of regulatory and market incentives on drug development by multinational firms, As shown clearly by the data in the Boston study, this clearly includes both brand-name firms and generic firms, as both are pursuing cluster-based models of drug development. The resulting analytical model focuses on drug development driven by purposeful policy, and cumulative vetting of serial products by regulators and the market.
Described in detail in a forthcoming book, drug clusters denoted ‘on deck’, ‘at bat’, and ‘home run’ represent a theoretical mock-up of how drug clusters grow in time from a spatiotemporal perspective. In this model, product-patent clusters begin their life as single-drug products or small groupings at the most innovative end of the index and, with increased vetting of products in the cluster over time by regulators and the market grow in scope to encompass an increasing number of products and patents. As this occurs, the cluster may be anticipated to ‘swing up and to the left’ of the innovation index, moving from a high level of innovation with a low number of patents and listed patents to first a moderate and then a much lower level of innovation but with greater spatiotemporal characteristics. The model shown here is for 2,087 drug approvals over an eight year study period; similar results have been obtained using patents and chemical components.
Fig. 4. Combining Innovation Index and Product Cluster Models to Study Portfolio-Based Drug Development and Hedging.Product clusters are hypothesized to begin life at the most innovative end of the spectrum, with few patents and a small or negligible number of listed patents. Over time, and increased vetting by regulators and the market, the cluster expands to include more products, patents and listed patents but, as a whole becomes less and less innovative. The desired end point (the “home run”) is a substantial but low level cluster with numerous products, patents and listed patents, and the widest scope of market exclusivity and cumulative patent protection. Prior to this point, clusters are “at bat”, as they reach a critical state prior to moving into an expanded spatiotemporal state or merely “on deck” as firms await critical regulator and market vetting.An important observation with regard to product-patent drug clusters is that as a given cluster grows spatiotemporally over time, it grows not only in scope but also in the scale of the interrelatedness of its functional components over time.
As noted in 2001 by Kingston and later by Polk & Parchomovsky and, notably, the EC Pharmaceutical Sector Inquiry, the strength of patent portfolios and related product clusters from an intellectual property law perspective is “greater than the sum of its parts”. This “more is different” element, originally described in 1972 by PW Anderson, is characteristic of complex systems, including complex legal systems such as those described by JB Ruhl and many others in the mid-1990s. As noted in Part 1, we have referred to the complex multidirectional interrelationships and interdependencies between drug development, drug regulation and intellectual property law in our previous McGill and Berkeley studies as a regulated Therapeutic Product Lifecycle, or rTPL.
Of interest, our data show that the profit of a given molecule is strongly related to the number of patents, regulatory approvals, the number of patents listed on the register, and the range of drugs and regulatory approvals that are legally related but separated by only very minimal changes to existing uses and chemistry. This is true even for drugs thought be innovative such as those with First in Class and New Active Substance (New Chemical Entities), owing to regulatory loopholes.
Somewhat surprisingly, in light of global innovation policy over the last 50 years, the greater the number and scope of these metrics the lower is the calculated level of innovation of a basket of drugs in a product cluster. As market and regulator vetting increases with time, one sees generally (1) more patents, regulatory approvals, fractional patent listing, patent classifications per marketed drug, (2) a greater follow-on-to-new drug ratio in the cohorts studied, and (3) greater profitability for less innovative drugs.
Indeed, drug clusters driven by line extension, or follow-on, drugs are proving to be very profitable. For example, we found that the vast majority of approval, patenting and chemical development activity associated with brand pharmaceutical products is directed to the development of Me Too drugs, in particular follow-on Me Too drugs. Of the top 25 most profitable drugs in 2006, 48% (12) were line extension Me Too drugs. The combined sales of these drugs were US $45.7 billion dollars. Follow-on First in Class drugs represented 28% of the top 25 selling drugs, and 7 of the top 15 selling drugs. Profit on this group of drugs was US $39.7 billion dollars in 2006.
Combined, follow-on Me Too and First in Class drugs accounted for 19 of 25 of the most profitable drugs, with total sales of US $85.5 billion in a single year.
From a "science of law" perspective, a major advantage of the rTPL and product cluster models is that there is, in fact, considerable empirical evidence available for study for all interested parties. This includes the various types of new and follow-on drugs, patents, patent classifications, listed patents, related litigation, as well as the relation of these metrics to one another over time. This wide array of empirically observable metrics and the observation that they change over time sets up the possibility that, akin to protein folding and X-ray crystallography models, the data can be expressed in 3-D spatiotemporal form.
Indeed, the goal of our empirical work over the last four years involving new and follow-on drugs, patent trees, patent types, WHO Anatomical Therapeutic Classification (ATC) data, litigation data, the innovation index, and product cluster model is to convert the cumulative data into 3-D formats used in the medical sciences. For example, the protein-RNA model presented below underscores the utility of 3-D “rotational” models to both identify and quantify the complex structural and functional characteristics in a given network of biological components, here those between an RNA strand and protein components in the context of Multiple Sclerosis.
Fig. 5. Medical Sciences Template for Rotational 3-D Spatiotemporal Models of Cluster-Based Drug Development. From: Joint Evolutionary Tree Method for Study of MS.
As discussed previously, rotational 3-D drug product-drug patent cluster models would be particularly useful to policy-makers and law-makers in order to enable visual and numerical quantification of the impact of intellectual property law on drug development, generic entry, and access to essential medications in the same manner that one might look at a car from behind (highlighting the ‘gas tank,’ or original drug product and associated patent tandems) as well as from the side (from the rear to the front of the vehicle, underscoring how and when approvals, patents, and listed patents increase over time with market and regulator vetting).
In this manner, extrapolating the empirical techniques conventionally used in the hard sciences to the study of law, including patent law and innovation policy, offers an important opportunity to not only quantify the effect of a given piece of law or policy, but also to help determine the vires of such laws after they have been put in motion and to guide law reform efforts in light of objective arm’s length evidence.
It is hoped this series of articles has shed some light on the utility of traditional scientific methods for quantitative and qualitative assessment of patent value, and whether laws made decades ago to enhance innovation in the pharmaceutical sector and to facilitate timely generic entry are producing intended effects, unintended effects, or some combination of both. A second consideration is whether empirical legal research can be a valuable tool to assess the convergence of public health law and industrial law such as that which has evolved in most developed nations over the last three decades.
In any event, it will be interesting to see whether, as in other fields such as medicine and engineering that are accustomed to taking an “evidence-based” approach to problem identification and problem solving, whether we in the legal field may also include empirical evidence in our expanding toolkit of legal assessment and interpretation methods.
Tuesday, January 03, 2012
Editor's note: This is the second installment of a three-part series.
In new work by our group, we have outlined a tandem of new methodological tools to identify and quantify new and follow-on drugs and patent valuation. The first is a harmonized method to quantify drug approvals, patents and associated chemical components that summarizes and extends our previous work on topic. The second provides a new “innovation index” that incrementally grades the value, not only for patents in the life sciences and other technology-intensive sectors, but also for associated regulatory approvals, chemical components, patent characteristics, etc. The innovation index values are based on evidentiary hurdles and prioritizations for several classes of “new” and “follow-on” drugs disclosed by drug regulators. As indicated by the titles of the articles, one focuses on the quantitative side while the other focuses on the qualitative side of the analysis.
The Boston Article presents a harmonized method to collect, compare, and quantify regulatory approval data from multiple cohorts of new and follow-on drugs. We looked in some detail at about 2,000 regulatory approvals, 5,000 patents, and 130 chemical components. The analysis encompasses all drug classes enumerated, described and prioritized by domestic drug regulators. The drug classes were gleaned from the usual literature reviews, supplemented by several hours of consultation with Health Canada regulators and review of Health Canada Guidance Documents on topic. A second purpose of this work was to go beyond simplified descriptors of new and follow-on drugs found in the literature, to categorize classes of new, line extension and generic approvals according to the nomenclature used by regulators themselves. This latter point is relevant is relevant, as we found different scholars use different approaches and nomenclatures, sometimes very different, and that these approaches were not always the same as those used by regulators themselves.
Read the rest of this post . . . .The innovation index work described in the companion Santa Clara Article was driven by the fact that almost all published patent assessment methods measure innovation using primarily quantitative methods, otherwise referred to as ‘counting methods.’ For reasons discussed in work on topic by Kingston at Trinity, Lemley at Stanford and Polk and Parchomovsky at Penn, and the sources cited therein, while quantitative models are widely considered to be problematic, a model that assesses patent value using qualitative methods that track, or are at least designed to track social benefits, has not yet emerged. A second reason for developing the two methods is that is that even when many scholars and commentators do look at the “innovative” aspect of the data, they simply accept data provided by regulators in their respective annual reports in a per se manner.
While developing a novel scientific method for either obtaining or analyzing legal data is fraught with its own problems, this step nevertheless forms a necessary component of the “trial and error” heuristic typical in the hard sciences. As more individuals with prior experience in medical science enter law and legal scholarship, we will undoubtedly see more and more scientific studies of law, including importing of fundamental mathematical, statistical, curve fitting, modeling, and graphing methods. In the Santa Clara paper, a qualitative innovation index is reported that we hope may fill some of the gaps in patent valuation. One of the figures from this work, relating to regulatory approvals, is shown below.
Fig. 1. Innovation Index Data for Total Approval Cohort. Bar graphs showing the number of total approvals expressed as a function of the level of innovation (LOI) before (a) and after (b) of generic approval data. c Brand approvals expressed as a function of LOI. Solid line is a fit of the data to a single exponential function. d Cumulative normalized brand approvals expressed as a function of LOI. Solid line is fit using a sigmoidal function.The figure presents data for many classes of new and follow-on drugs and categorizes these classes using a linear scheme. Raw data values are given in the Y axis of Fig. 1a and 1b, the difference being generic data were subtracted in Fig. 1b to isolate data only from ‘innovator’ firms. The X axis in both panels represents the innovation index data. The innovation index data are referred to as transformed data, because the raw data pertaining to drug approvals, drug patents, and chemical components are transformed into qualitative values on a linear scale (0-15) using the methods outlined in the Santa Clara paper.
The strengths and weaknesses of the hybrid “subjective-objective” nature of data transformation, and the similarities to subjective-objective hybrid models that are already widely accepted for use in the fields of drug approval, patent grant, and the adjudication of patent claims by the courts are discussed more fully there.
Data can, of course, be fit to many types of numerical functions, linear or non-linear; increasing or decreasing. Fig. 1c above shows that the data in the bar graph of Fig. 1b fit to a declining exponential function. As can be seen by the close fit of the data to the function, the choice of an exponential relationship was well founded. The data are interesting as they demonstrate an exponential decline in the numbers of drugs in classes with relatively high innovation index values. In other words, the vast majority of drugs approved in Canada have a very low index value, and indeed are primarily follow-on Me Too drugs.
Fig. 1d represents the normalized cumulative data fit to a sigmoid (S-shaped log) function, which is a numerical approximation of “how fast” the innovation index data rise to their maximal peak. A fast rise, as we see here, suggests that most of the drugs approved over nearly a decade are in the low index bins and that the data in the low index bins accumulate much more rapidly than do the data in the higher index bins. Similar, though not identical, results were obtained with several indicator Cohorts studied, including a wide Cohort of 2,087 drugs, a narrower Cohort of 95 of the most profitable drugs, and a similar Cohort of associated patents and chemical components.
The innovation index provides a means of weighing legitimate patent protection against perceived societal benefit. As such, it affords a qualitative measure of the innovative nature of drug patents that, when compared to counting methods, may more adequately reveal the outcome of development incentives for firms and regulating bodies insofar as these parties have conflicting interests.
The results from our analysis indicate that it is not the most innovative or even strongly innovative drugs that are attracting the greatest firm patenting effort. Rather, when gauged against development priorities publicly disclosed by regulators and governments, including specifically in the United States and Canada where linkage first came into force, it is the least innovative drugs of all classes investigated that display the strongest regulatory approval and patenting efforts. This issue is touched on in more detail in Part 3 of the series.
In this manner, our data are contrary to the established dogma that the strength of patent protection is proportional to the "strength" of innovation of a given product. As discussed more fully in Part 3, the data obtained also support the conclusion that cluster-based, or portfolio-based, drug development has become the dominant innovation strategy for both brand and generic firms. Indeed, data from our Boston study demonstrates conclusively that generic firms are accruing more patents than their brand counter-parts, especially in the new drug approval category.
Finally, the data suggest that the perception on the part of governments and the public to the effect that societal benefit comes as a kind of “natural consequence” of patenting may need to be reconsidered.
Saturday, December 03, 2011
Patent valuation has become a hot button issue of late, particularly in the area of pharmaceuticals. In the effort to win the global innovation race, substantial policy and economic efforts are being made by developed and developing nations alike in support of innovation, both in terms of understanding it and making more of it when innovation does occur.
The issue of patent valuation presents to an increasingly educated lay audience as a kind of titanic contest of wills between those who prefer big incentives for innovation and those who focus of the social benefits, or outcomes, of innovation.
Many studies of innovation and patent valuation use economic models to assess the business value associated with patents at a given point in time, as well as ways of maximizing value from those patents. Although there are certainly many skeptics, innovation and patenting have nevertheless become synonymous in economic discussions of national productivity and prosperity in a wide variety of debates, including scholarly, political, civil service, and in the media.
Read the rest of this post . . . .In the world of life sciences products, a distinction can be made between an economic analysis - even one cast in a law and economics light - and a patent law analysis. This is because one is primarily (though not exclusively) in service of utilitarian benefit and the other is primarily (though not exclusively) in service of equity, equality and the terms of the traditional patent bargain. As instructed by the courts when pharmaceutical patents are at issue, the patent bargain is itself to be interpreted through the public health mandate as it is bound by the unique trifecta of patent law, food and drug law and linkage law.
This places patent valuation front and center of any discussion of law reform focused on pharmaceutical innovation, as well as discussions and law reform aimed at reducing drug costs and expenditures. The fact that, unlike in many other industries, follow-on products may offer little benefit compared to existing products raises the bar on this discussion, as does the fact that patents associated with these products can be used as more of a sword than a shield to evergreen older product lines and keep drug prices high.
Because the availability, costs and expenditures of drugs are regulated by such a complex array of legal, policy and political vehicles, their analysis is quite amenable to “complexity”-based frameworks, which by design place significant emphasis on feedback loops between multiple interrelated nodes.
In this case the nodes, or spheres to use the nomenclature of Walzer, are industrial, economic, public health, and political in nature but also play out in numerous intersecting ways in statutory, regulatory, policy, and judicial terms. In our Berkeley study, we presented the model below for the development, consumption and regulation of drug products, referring to it as a regulated Therapeutic Product Lifecycle (rTPL).
Through diagrams such as these, one can see that patent rights and incentives permeate all stages of the rTPL. As we have noted elsewhere, even assuming a relatively linear innovation process, because of regulatory incentives that allow the public to gain access to therapeutic products prior to conventional Phase 3 trials, and because linkage laws allow for the development of clusters of interrelated new and follow-on drugs and associated patents, the regulatory lifecycle for drugs has become at once increasingly complex, intertwined, and collapsed. Linkage laws in particular complicate the picture as they are intended to both facilitate industrial development in the form of new drugs and to satisfy the public health mandate by yielding cost savings on generic entry.
One might argue that the convergence of public health and industrial policy of this nature calls for a clear and concise set of policy levers governing the complex innovation ecology for therapeutic products, particularly in jurisdictions where the availability of both brand and generic drugs are regulated by linkage laws.
Yet, as noted in the recent decision of the High Court of Delhi in India, where (like the E.U.) linkage was rejected, the court held that worldwide there is a "raging debate on whether patent linkage should be permitted," concluding there is "no uniformity in the policy of different countries."
In North America, the birthplace of linkage, the Supreme Court of Canada held in its seminal decisions in Biolyse and AstraZeneca that linkage regulations tying generic entry to brand-name patents must be made in a patent-specific manner. The court's pronouncement highlights the importance of the qualitative and quantitative nature of the balance inherent to the patent bargain, especially when read in light of the so-called “special provisions” of linkage laws when parsing pharmaceutical patents.
As pointed out by the Global Consortium on Pharmaceutical Linkage in a recent article, patent law is also antecedent to linkage in the United States, which was the first jurisdiction globally to promulgate linkage laws. This was made clear by the seminal reports of the Committee on the Judiciary (COJ) and the Committee on Energy and Commerce (CEC) prior to the coming into force of Hatch Waxman. Both the COJ and CEC made it clear that the twin policy goals of linkage laws were to encourage the development of “new and innovative” drugs and to facilitate the “timely” entry of generic drugs.
Both of these competing policy goals depend on patents, and so again we arrive at a pivotal role for patent valuation in determining outcomes related to the twin policy goals at issue.
So, what evidence is there to assess whether these two policy goals have been met by patent, food and drug, and linkage laws? What evidence is there to determine the role of “strong” and “weak” patents in producing outcomes, including unintended consequences that may have been completely unanticipated by law-makers at the time pharmaceutical law and policy came to the fore in the early 1980s and 1990s?
This will be the subject of Parts2 and Part 3 of the series.
Thursday, December 01, 2011
Take my friends and my home - as an outcast I'll roam: Take the money I have in the bank: It is just what I wish, but deprive me of fish, And my life would indeed be blank.This ichthyophile brother would surely be alarmed at the crisis now facing wild salmon stocks on the Pacific coast of North America.
Salmon can contract an influenza-related virus that causes infectious salmon anemia ("ISA"). For the past few decades ISA has been devastating salmon populations from Norway and Scotland to the Canadian Maritimes and Chile, sometimes killing more than 9 out of every 10 fish. Critics of salmon farming have blamed the spread of ISA on the high densities of fish kept together in ocean-borne cages, along with frequent piscine jailbreaks into the wild.
In October, 2011, ISA was diagnosed among wild pacific salmon in British Columbia by the ISA Reference Laboratory at the Atlantic Veterninary College, in Prince Edward Island. Although these diagnoses were quickly disputed by the Canadian Food Inspection Agency, it now appears that Canada may have made similar diagnoses as long ago as 2002. If so, it seems that Canada failed in its obligations to inform the United States and the World Organization for Animal Health.
Salmon farming is especially controversial on the Pacific coast of North America, because of the existence of a thriving wild salmon fishery. Fears that escapees from fish farms there could spread diseases to these wild populations have generally been dismissed by fish farmers.
If ISA has indeed infected wild Pacific salmon populations, Carroll's other, ichthyophobic, brother would surely be delighted:
What? a higher delight to be drawn from the sight of fish full of life and of glee? What a noodle you are! ‘Tis delightfuller far to kill them than let them go free!Too bad Dudley Do-Right did not do right by the salmon.
More biolaw at LEXVIVO.
The I=PAT formula is an identity. I represents environmental impact, P population, A affluence, and T technology. While human population (that is, number of people) and affluence (that is, wealth per person) have tended to push I upwards over the last few thousand years, the technology factor (impact per wealth) has tended to decrease I by providing increasingly efficient means for accomplishing tasks. Because I is calculated as the product of P, A, and T, each factor is equally important.
Thus, while population growth certainly contributes to environmental impact, so do affluence growth and technological improvement. Welcome, G. Septem. Now that you have joined us, we will watch with fascination how wealthy you become, and how quickly technology improves during your lifetime.
More biolaw at LEXVIVO.
Monday, September 26, 2011
Friday, September 16, 2011
SEC. 33. LIMITATIONS ON ISSUANCE OF PATENTSNo one yet knows what "directed to or encompassing a human organism" means. The United States Patent and Trademark Office will have the first opportunity to apply this restriction as the initial arbiter of patent applications. Inevitably, the federal courts will weigh in to provide more authoritative interpretations. Eventually, Congress may have to amend this provision to clarify it. Meanwhile, the inclusion of this restriction on patenting "a human organism" directly within the patent statute strongly signals that at least some biotechnological advances have unsettled both Congress and the President.
(a) LIMITATION.-Notwithstanding any other provision of law, no patent may issue on a claim directed to or encompassing a human organism.
(b) EFFECTIVE DATE.-
(1) IN GENERAL.-Subsection (a) shall apply to any application for patent that is pending on, or filed on or after, the date of the enactment of this Act.
(2) PRIOR APPLICATIONS.-Subsection (a) shall not affect the validity of any patent issued on an application to which paragraph (1) does not apply.
Friday, August 12, 2011
Tuesday, August 02, 2011
Question: What's the difference between a patent attorney and a tax attorney?Answer: Patent attorneys are like tax attorneys, but without the scintillating personalities!
Why would a company rent an office in a tiny town in East Texas, put a nameplate on the door, and leave it completely empty for a year? The answer involves a controversial billionaire physicist in Seattle, a 40 pound cookbook, and a war waging right now, all across the software and tech industries. We take you inside this war, and tell the fascinating story of how an idea enshrined in the US constitution to promote progress and innovation, is now being used to do the opposite.
Wednesday, July 06, 2011
As discussed previously on LEXVIVO, on December 17, 2010, Prometheus, Inc., a San Diego-based biotechnology company, prevailed in appealing a district court's grant of summary judgment that had found claims in Prometheus' exclusively licensed patents (U.S. Pat. Nos. 6,355,623 and 6,680,302) invalid as drawn to non-statutory subject matter under 35 U.S.C. §101. In Prometheus v. Mayo, a unanimous panel of the Federal Circuit "again [held] that Prometheus' method claims recite patentable subject matter under §101." The court's previous finding that Prometheus' claims constituted statutory subject matter was successfully appealed by defendants-appellees Mayo Collaborative Services and Mayo Clinic Rochester (hereafter, "Mayo") to the Supreme Court, which vacated and remanded the Federal Circuit's decision on April 29, 2010, "for further consideration in light of Bilski v. Kappos," a business method patent case the Supreme Court had decided the day before. It would appear that the Supreme Court has now called two strikes on the Federal Circuit on this issue.
The claims at issue cover methods for determining the optimal dosage of thiopurine drugs, such as 6-mercaptopurine and azathiopurine, used to treat inflammatory bowel diseases that include Crohn's disease and ulcerative colitis. For example, claim 1 of the '623 patent involves (1) administering a drug capable of producing 6-thioguanine inside a patient suffering from a gastrointestinal disorder, (2) determining the concentration of 6-thioguanine in the patient's blood, and (3) indicating the need to increase or decrease the drug's dosage depending on whether the drug's blood concentration is outside of the therapeutically desired range of 230-400 pmol per 80,000,000 red blood cells.
Now, the Supreme Court will have an opportunity to clarify the patentability of inventions directed to methods of diagnosing medical conditions, as well as those that combine such diagnostic methods with methods of treatment. Any optimism the biotechnology industry might have derived from the Federal Circuit's December 17, 2010, decision in Prometheus v. Mayo may now be tempered by the specter of the Supreme Court adopting the argument that Justice Stephen Breyer (joined by now-retired Justices John Paul Stephens and David Souter) made in his vigorous dissent to the dismissal of the writ of certiorari of a kindred case, Laboratory Corporation v. Metabolite Laboratories, Inc.. In his dissent, Breyer described the medical diagnostic method contested in that case as follows:
A similar conclusion in Prometheus v. Mayo by a majority of the Supreme Court could redraw the boundaries of patentable biological subject matter in United States patent law.
At most, respondents have simply described the naturallaw at issue in the abstract patent language of a "process." But they cannot avoid the fact that the process is no more than an instruction to read some numbers in light of medical knowledge.
See more biolaw at LEXVIVO.
Wednesday, June 15, 2011
Canada geese represent a serious urban menace. Their molting season presents local governments a short, annual window of opportunity to respond by culling geese en masse. After an outcry over the failure in 2010 to convert culled geese into low-cost, high-protein food, New York officials will not consign this year's harvest to the landfill. Instead, geese from Brooklyn's Prospect Park are destined for slaughter and distribution to food banks.