Patents – a practical perspective

Patent Update is a regular column dedicated to the complex issues that affect patents in the genomics and proteomics field. In each issue, there are two sections compiled by patent attorneys. The first section, Patents – a Practical Perspective, is a commentary on current issues, landmark patents, useful patent resources and how to search them, and legislative changes that impact the pharma and biotech industries. The second section, Patent News, provides brief synopses of recently issued patents and other patent events, and their significance to drug discovery R&D.     

Patentes fúngicas: de Pasteur a nuestros días

At the end of the 19^th century, the American Patent Office granted the patent known as “Pasteur's application”, claiming the protection of a yeast strain. Since that date, the debate around biotechnology patents, especially for those that affect living organisms or part of them, has grown exponentially.In the present article, the Patent Law is reviewed, pointing out the particular problems about fungi or parts of them. Also, some of the fungus patents are discussed from the perspective of the ethical, economical, social and environmental aspects of these kind of patents.     

Annotated Chemical Patent Corpus: A Gold Standard for Text Mining

Exploring the chemical and biological space covered by patent applications is crucial in early-stage medicinal chemistry activities. Patent analysis can provide understanding of compound prior art, novelty checking, validation of biological assays, and identification of new starting points for chemical exploration. Extracting chemical and biological entities from patents through manual extraction by expert curators can take substantial amount of time and resources. Text mining methods can help to ease this process. To validate the performance of such methods, a manually annotated patent corpus is essential. In this study we have produced a large gold standard chemical patent corpus. We developed annotation guidelines and selected 200 full patents from the World Intellectual Property Organization, United States Patent and Trademark Office, and European Patent Office. The patents were pre-annotated automatically and made available to four independent annotator groups each consisting of two to ten annotators. The annotators marked chemicals in different subclasses, diseases, targets, and modes of action. Spelling mistakes and spurious line break due to optical character recognition errors were also annotated. A subset of 47 patents was annotated by at least three annotator groups, from which harmonized annotations and inter-annotator agreement scores were derived. One group annotated the full set. The patent corpus includes 400,125 annotations for the full set and 36,537 annotations for the harmonized set. All patents and annotated entities are publicly available at www.biosemantics.org.     

Strategic mining of cyanobacterial patents from the USPTO patent database and analysis of their scope and implications

Patent analysis with the help of the strategic mining of patents from databases is important and useful within the framework of application-oriented research and its commercialization. In the analysis reported here, we have mined cyanobacterial patents from the patent database of the United States Patent and Trademark Office (USPTO). In order to make an assessment of the commercial potentials of cyanobacteria, we conducted the patent search (from 1976 to April 2006) using certain generic terms and the 84 genera of cyanobacteria as keywords. The search was performed in two major ways – searching the abstracts and claims of the patents cumulatively and searching the entire patent documents by the mode of ‘all fields’ in USPTO. In the abstract- and claims-based search, 234 patents were obtained after the removal of overlapping patents among the keywords. An additional 31 patents were added following the ‘all fields’ search; these patents were not covered in the search that was based on abstracts and claims. The entire package of 265 patents, of which 244 were related to cyanobacteria, was then analyzed. Information derived from these patents identified five major areas of cyanobacterial utilization. Cyanobacteria have been patented as a source of a wide spectrum of products, for medical, agriculture and environmental applications, for gene-based products, for methods of cultivation and for methods of control. The chronological development in granting cyanobacterial patents was also traced. This study demonstrates that such strategic mining and analysis of patent data can be used as an index for future development.     

Metastasizing patent claims on BRCA1

Many patents make claims on DNA sequences; some include claims on oligonucleotides related to the primary patented gene. We used bioinformatics to quantify the reach of one such claim from patent 4,747,282 on BRCA1. We find that human chromosome 1 (which does not contain BRCA1) contains over 300,000 oligonucleotides covered by this claim, and that 80% of cDNA and mRNA sequences contributed to GenBank before the patent application was filed also contain at least one claimed oligonucleotide. Any “isolated” DNA molecules that include such 15 bp nucleotide sequences would fall under the claim as granted by the US Patent and Trademark Office. Anyone making, using, selling, or importing such a molecule for any purpose within the United States would thus be infringing the claim. This claim and others like it turn out, on examination, to be surprisingly broad, and if enforced would have substantial implications for medical practice and scientific research.     

An assessment of emerging molecular farming activities based on patent analysis (2002∼2006)

The products of Plant Molecular Farming are recombinant proteins or their metabolic products. In this study, patent data was employed to assess industrial trend in the research and innovation process of Plant Molecular Farming within national and international context. The US Patent and Trade Organization (USPTO), the European Patent Office (EPO) issued a total of 585 patents covering Plant Molecular Farming from 2002 through 2006. By nationality, US inventors predominated as recipients of PMF patents, followed by Germany, Denmark, and Japan. The PMF patents were catagorized in five major areas of research namely pharmaceutical and nutraceuticals with 170 patents (31%) and plant expression tools and methods for alternative production systems with 169 patents (29%) were the dominating patent applications, followed by 102 patent claims associated with antibodies (17%), 71 patents of industrial molecules (12%), 48 patents of vaccines (8%), and finally 18 patents related to post-translational protein glycosylation (3%). The greatest proportion of patentees was of US origin (52%), and PMF associated patenting activities at the USPTO and EPO were dominated with 67% by private organizations. Disclaimer: The views expressed in this study do not necessarily reflect those of the European Commission.     

Evaluation of brazilian biotechnology patent activity from 1975 to 2010

The analysis of patent activity is one methodology used for technological monitoring. In this paper, the activity of biotechnology-related patents in Brazil were analyzed through 30 International Patent Classification (IPC) codes published by the Organization for Economic Cooperation and Development (OECD). We developed a program to analyse the dynamics of the major patent applicants, countries and IPC codes extracted from the Brazilian Patent Office (INPI) database. We also identified Brazilian patent applicants who tried to expand protection abroad via the Patent Cooperation Treaty (PCT). We had access to all patents published online at the INPI from 1975 to July 2010, including 9,791 biotechnology patent applications in Brazil, and 163 PCTs published online at World Intellectual Property Organization (WIPO) from 1997 to December 2010. To our knowledge, there are no other online reports of biotechnology patents previous to the years analyzed here. Most of the biotechnology patents filed in the INPI (10.9%) concerned measuring or testing processes involving nucleic acids. The second and third places belonged to patents involving agro-technologies (recombinant DNA technology for plant cells and new flowering plants, i.e. angiosperms, or processes for obtaining them, and reproduction of flowering plants by tissue culture techniques). The majority of patents (87.2%) were filed by nonresidents, with USA being responsible for 51.7% of all biotechnology patents deposited in Brazil. Analyzing the resident applicants per region, we found a hub in the southeast region of Brazil. Among the resident applicants for biotechnology patents filed in the INPI, 43.5% were from S?o Paulo, 18.3% were from Rio de Janeiro, and 9.7% were from Minas Gerais. Pfizer, Novartis, and Sanofi were the largest applicants in Brazil, with 339, 288, and 245 biotechnology patents filed, respectively. For residents, the largest applicant was the governmental institution FIOCRUZ (Oswaldo Cruz Foundation), which filed 69 biotechnology patents within the period analyzed. The first biotechnology patent applications via PCT were submitted by Brazilians in 1997, with 3 from UFMG (university), 2 from individuals, and 1 from EMBRAPA (research institute).     

生物能源领域国际相关专利分析

随着石油资源的日益枯竭,近年来生物能源技术的开发引起了全球各界的广泛重视,加之专利保护意识的增强,生物能源领域的专利数量迅速增长,对专利信息的分析可以了解生物能源技术的发展现状和趋势,为技术创新和战略发展提供参考。本文选取目前生物能源中的三种重要技术――生物乙醇、生物柴油和生物制氢技术,利用专利计量分析的方法对其发展态势进行了研究。研究内容包括：专利申请的时间分布和空间分布,被引专利情况,主要技术领域,以及重要专利权人及其相关信息,从专利分析的角度揭示近年来这三种生物能源技术的研发状况。     

The lone inventor: low success rates and common errors associated with pro-se patent applications

A pro-se patent applicant is an inventor who chooses to represent himself while pursuing ("prosecuting") a patent application. To the author's knowledge, this paper is the first empirical study addressing how applications filed by pro-se inventors fare compared to applications in which inventors were represented by patent attorneys or agents. The prosecution history of 500 patent applications filed at the United States Patent and Trademark Office were analyzed: inventors were represented by a patent professional for 250 of the applications ("represented applications") but not in the other 250 ("pro-se applications"). 76% of the pro-se applications became abandoned (not issuing as a patent), as compared to 35% of the represented applications. Further, among applications that issued as patents, pro-se patents' claims appear to be narrower and therefore of less value than claims in the represented patent set. Case-specific data suggests that a substantial portion of pro-se applicants unintentionally abandon their applications, terminate the examination process relatively early, and/or fail to take advantage of interview opportunities that may resolve issues stalling allowance of the application.     

Gene patents and capital investment

Will the US Supreme Court''s ruling that genes can no longer be patented in the USA boost venture capital investment into biotech and medical startup companies?Three years ago, Noubar Afeyan, managing partner and CEO of Flagship Ventures, an early-stage venture capital firm in Cambridge, Massachusetts, USA, was working with a biotech start-up company developing techniques for BRCA gene testing for breast cancer risk that avoided the patents held by Myriad Genetics, a molecular diagnostics company in Salt Lake City (Utah, USA) and the only operator in the field. However, despite the promise of the start-up''s techniques, investors were put off by Myriad''s extensive patent portfolio and fiercely defensive tactics: “A lot of investors were simply not willing to take that chance, even though our technology was superior in many ways and patentably different,” Afeyan said. The effort to launch the start-up ultimately failed.…it is also not clear how the Supreme Court''s ruling will affect the […] industry at large, now that one of the most contested patents for a human gene has been ruled invalidAfeyan believes the prospects for such start-ups improved on the morning of 13 June 2013 when the US Supreme Court ruled in an unanimous vote that Myriad''s fundamental patents on the BRCA1 and BRCA2 genes themselves are invalid, opening up the field to new competitors. The court''s ruling, however, validated Myriad''s patents for BRCA cDNA and methods-of-use.The court''s decision comes at a time when venture capital investment into the life sciences is projected to decline in the years ahead. Some believe that the court''s decision sets a precedent and could provide a boost for products, diagnostics and other tests under development that would have been legally difficult in the light of existing patents on human and other DNA sequences.The US Patent Office issued the original patents for the BRCA 1 and BRCA2 genes in 1997 and 1998 for the US National Institute of Environmental Health Services, the University of Utah and Myriad Genetics. One year earlier, Myriad had launched its first diagnostic test for breast cancer risk based on the two genes and has since aggressively defended it against both private and public competitors in court. Many universities and hospitals were originally offering the test for a lower cost, but Myriad forced them to stop and eventually monopolized BRCA-based diagnostics for breast cancer risk in the USA and several other countries.“Myriad did not create anything,” Justice Clarence Thomas wrote in the Supreme Court''s decision. “To be sure, it found an important and useful gene, but separating that gene from its surrounding genetic material is not an act of invention.” Even so, the court did uphold Myriad''s patents on the methodology of its test. Ron Rogers, a spokesman for the biotech firm, said the Supreme Court had “affirmed the patent eligibility of synthetic DNA and underscored the importance and applicability of method-of-use patents for gene-based diagnostic tests. Before the Supreme Court case we had 24 patents and 520 claims. After the Supreme Court decision, we still have 24 patents. […] [T]he number of our patent claims was reduced to 515. In the Supreme Court case itself, only nine of our 520 patent claims were at issue. Of the nine, the Supreme Court ruled that five were not patent-eligible and they ruled that four were patent-eligible. We still have strong intellectual property protection surrounding our BRCA test and the Supreme Court''s decision doesn''t change that.”Within hours of the ruling, capitalism kicked into high gear. Two companies, Ambry Genetics in Alieso Viejo, California, and Gene by Gene Ltd in Houston, Texas, USA, announced that they were launching tests for the BRCA1 and BRCA2 genes for less than the US$3,100 Myriad has been charging privately insured patients and US$2,795 for patients covered by Medicare—the government health plan for the elderly and disabled. Several other companies and universities also announced they would be offering BRCA testing.Entrepreneur Bennett Greenspan, a managing partner of Gene by Gene, explained that his company had been poised to offer BRCA testing if the Supreme Court ruled against Myriad. He said, “We had written a press release with our PR firm a month before the release of the Supreme Court with the intention that if the Supreme Court overruled the patent or invalidated the patent that we would launch right away and if they didn''t, we would just tear up the press release.” His company had previously offered BRCA gene testing in Israel based on guidelines from the European Union.Myriad Genetics has not given up defending its patents, however. On 9 and 10 July 2013, it slapped Ambry and Gene by Gene with lawsuits in the US District Court in Salt Lake City for allegedly infringing on patents covering synthetic DNA and methods-of-use related to the BRCA1 and BRCA2 genes. Rogers commented that the testing processes used by the firms “infringes 10 patents covering synthetic primers, probes and arrays, as well as methods of testing, related to the BRCA1 and BRCA2 genes.”On 6 August 2013, Ambry countersued Myriad, arguing that the company “continues a practice of using overreaching practices to wrongfully monopolize the diagnostic testing of humans'' BRCA1 and BRCA2 genes in the United States and to attempt to injure any competitor […] Due to Myriad''s anticompetitive conduct, customers must pay significantly higher prices for Myriad''s products in the relevant market, often nearly twice as high as the price of Ambry''s products and those of other competitors” [1].Just as the courts will have to clarify whether the competitors in this case infringe on Myriad''s patents, it is also not clear how the Supreme Court''s ruling will affect the biotech and diagnostics industry at large, now that one of the most contested patents for a human gene has been ruled invalid. In recent years, venture capital investment into the life sciences has been in decline. The National Venture Capital Association and the Medical Innovation & Competitiveness Coalition reported from a survey that, “An estimated funding loss of half a billion dollars over the next three years will cost America jobs at a time when we desperately need employment growth” [2]. The survey of 156 venture capital firms found that 39% of respondents said they had reduced investment in the life sciences during the previous three years, and the same proportion intended to do so in the next three years. “[US Food and Drug Administration] FDA regulatory challenges were identified as having the highest impact on these investment decisions,” the report states, adding that many investors intended to shift their focus from the US towards Europe and the Asia/Pacific region.Another report from the same groups explains how public policy involving the FDA and other players in “the medical innovation ecosystem”—including the US patent system, public agencies, tax policy, securities regulation, immigration laws and private groups such as insurers—affect the decisions of investors to commit to funding medical innovation [3].Some investors think that the court decision about the patentability of human DNA will increase confidence and help to attract investors back to the life sciencesSome investors think that the court decision about the patentability of human DNA will increase confidence and help to attract investors back to the life sciences. “The clarity is helpful because for the longest time people didn''t do things because of ambiguity about whether those patents would be enforceable,” Afeyan said. “It''s one thing to not do something because of a patent, it''s another to not do something because you know that they have patents but you''re not sure what it''s going to stop you from doing because it hasn''t been really fully fleshed out. Now I think it is reasonably well fleshed out and I think you will see more innovation in the space.”Others also appreciate the clarification from the Supreme Court about what is a patentable invention in regard to human genes and DNA. “The Myriad decision was a very solid reading of the underlying purpose of our patent law, which is to reward novel invention,” commented Patrick Chung, a partner with New Enterprise Associates, a venture capital firm in Menlo Park, California, which invested in 23andMe, a personal genomics company based in Mountain View (California, USA), and who serves on the 23andMe board.But not everyone agrees that the Supreme Court''s decision has provided clarity. “You could spin it and say that it was beneficial to create some certainty, but at the end of the day, what the Court did was reduce the scope of what you''re allowed to get patent claims on,” said Michael Schuster, a patent lawyer and Intellectual Property Partner and Co-Chair of the Life Sciences Group at Fenwick & West LLP in San Francisco, California, USA. “It''s going to be a continuing dance between companies, smart patent lawyers, and the courts to try to minimize the impact of this decision.”Kevin Noonan, a molecular biologist and patent lawyer with McDonnell Boehnen Hulbert & Berghoff LLP in Chicago, Illinois, USA, commented that he does not expect the Supreme Court decision will have much of an impact on venture investments or anything else. “This case comes at a time fortunately when biotechnology is mature enough so that the more pernicious effects of the decision are not going to be quite as harmful as they would if this had happened ten, 15 or 20 years ago,” he said. “We''re now in the ‘post-genomic'' era; since the late ‘90s and turn of the century, the genomic and genetic data from the Human Genome Project have been on publicly available databases. As a consequence, if a company didn''t apply for a patent before the gene was disclosed publicly, it certainly is not able to apply for a patent now. The days of obtaining these sequences and trying to patent them are behind us.”Noonan also noted that the Myriad Genetics patents were due to expire in 2014–2015 anyway. “Patents are meaningless if you can''t enforce them. And when they expire, you can no longer enforce them. So it really isn''t an impediment to genetic testing now,” he explained. “What the case illustrates is a disconnect between scientists and lawyers. That''s an old battle.”George Church, professor of genetics at Harvard Medical School (Boston, Massachusetts, USA) and Director of the Personal Genome Project, maintains that the Supreme Court decision will have minimal influence on the involvement of venture capitalists in biotech. “I think it''s a non-issue. It''s basically addressing something that was already dead. That particular method of patenting or trying to patent components of nature without modification was never really a viable strategy and in a particular case of genes, most of the patents in the realm of bio-technology have added value to genes and that''s what they depend on to protect their patent portfolio—not the concept of the gene itself,” he said. “I don''t know of any investor who is freaked out by this at all. Presumably there are some, because the stock oscillates. But you can get stock to oscillate with all kinds of nonsense. But I think the sober, long-term investors who create companies that keep innovating are not impacted.”Church suggests that the biggest concern for Myriad now is whole-gene sequencing, rather than the Supreme Court''s decision. “Myriad should be worrying about the new technology, and I''m sure they''ve already considered this. The new technology allows you to sequence hundreds of genes or the whole genome for basically the price they''ve been charging all along for two genes. And from what I understand, they are expanding their collection to many genes, taking advantage of next generation sequencing as other companies have already,” he said.Whatever its consequences in the US, the Supreme Court''s decision will have little impact on other parts of the world, notably Europe, where Myriad also holds patents on the BRCA genes in several countries. Gert Matthijs, Head of the Laboratory for Molecular Diagnostics at the Centre for Human Genetics in Leuven, Belgium, says that even though the US Supreme Court has invalidated the principle of patenting genes in America, the concept remains in Europe and is supported by the European Parliament and the European Patent Convention. “Legally, nothing has changed in Europe,” he commented. “But there is some authority from the US Supreme Court even if it''s not legal authority in Europe. Much of what has been used as arguments in the Supreme Court discussions has been written down by the genetics community in Europe back in 2008 in the recommendations on behalf of the European Society for Human Genetics. The Supreme Court decision is something that most of us in Europe would agree upon only because people have been pushing towards protecting the biotech industry that the pendulum was so way out in Europe.”Benjamin Jackson, Senior Director of legal affairs at Myriad Genetics, commented that Myriad holds several patents in Europe that are not likely to be affected by the Supreme Court''s ruling. “The patent situation both generally and for Myriad is a lot clearer in Europe. The European Union Biotech Directive very clearly says that isolated DNA is patentable even if it shares the same sequence as natural DNA,” he said. “Right now, it''s pretty uncontroversial, or at least it''s well settled law basically in Europe that isolated DNA is patentable.” However, while the Directive states that “biological material which is isolated from its natural environment or produced by means of a technical process” might be patentable “even if it previously occurred in nature”, the European Patent Office (EPO) in Munich, Germany, requires that the subject matter is an inventive step and not just an obvious development of existing technology and that the industrial application and usefulness must be disclosed in the application.Myriad has opened a headquarters in Zurich and a lab in Munich during the past year, hoping to make inroads in Europe. In some EU countries, Myriad offers its BRCA test as part of cancer diagnosis. In other countries, BRCA testing is conducted at a fraction of what Myriad charges in the USA, either because institutions ignore the patents that are not enforced in their jurisdictions, or because these countries, such as Belgium, were not included in the patent granted by the European Patent Office. Moreover, in various countries BRCA testing is only available through the healthcare system and only as part of a more extensive diagnosis of cancer risk. In addition, as Matthijs commented, “[t]he healthcare system in Europe is very heterogeneous and that''s also of course a big impediment for a big laboratory to try and conquer Europe because you have to go through different reimbursement policies in different countries and that''s not easy.”Ultimately, it seems the Supreme Court''s decision might turn out to have little impact on biotech firms in either the USA or Europe. Technological advances, in particular new sequencing technologies, might render the issue of patenting individual genes increasingly irrelevant.     

Evolution of microalgal biotechnology: a survey of the European Patent Office database

Microalgal biotechnology is an innovative sector in the field of biotechnology and has evolved exponentially in the last 100 years. With the aim of finding out the current situation of the sector and its development, patents on microalgal biotechnology were surveyed in Espacenet, the European Patent Office database. The objective of this study was to identify the main trends in microalgae-related patents in the most commercial genera: Chlorella, Spirulina, Dunaliella, Haematococcus and model organism Chlamydomonas.     

Enabling Policy Planning and Innovation Management through Patent Information and Co-Authorship Network Analyses: A Study of Tuberculosis in Brazil

Introduction

New tools and approaches are necessary to facilitate public policy planning and foster the management of innovation in countries'' public health systems. To this end, an understanding of the integrated way in which the various actors who produce scientific knowledge and inventions in technological areas of interest operate, where they are located and how they relate to one another is of great relevance. Tuberculosis has been chosen as a model for the present study as it is a current challenge for Brazilian research and innovation.

Methodology

Publications about tuberculosis written by Brazilian authors were accessed from international databases, analyzed, processed with text searching tools and networks of coauthors were constructed and visualized. Patent applications about tuberculosis in Brazil were retrieved from the Brazilian National Institute of Industrial Property (INPI) and the European Patent Office databases, through the use of International Patent Classification and keywords and then categorized and analyzed.

Results/Conclusions

Brazilian authorship of articles about tuberculosis jumped from 1% in 1995 to 5% in 2010. Article production and patent filings of national origin have been concentrated in public universities and research institutions while the participation of private industry in the filing of Brazilian patents has remained limited. The goals of national patenting efforts have still not been reached, as up to the present none of the applications filed have been granted a patent. The analysis of all this data about TB publishing and patents clearly demonstrates the importance of maintaining the continuity of Brazil''s production development policies as well as government support for infrastructure projects to be employed in transforming the potential of research. This policy, which already exists for the promotion of new products and processes that, in addition to bringing diverse economic benefits to the country, will also contribute to effective dealing with public health problems affecting Brazil and the World.     

Patenting of university and non-university public research organisations in Germany: evidence from patent applications for medical research results

Background

Patents are one of the most important forms of intellectual property. They grant a time-limited exclusivity on the use of an invention allowing the recuperation of research costs. The use of patents is fiercely debated for medical innovation and especially controversial for publicly funded research, where the patent holder is an institution accountable to public interest. Despite this controversy, for the situation in Germany almost no empirical information exists. The purpose of this study is to examine the amount, types and trends of patent applications for health products submitted by German public research organisations.

Methods/Principal Findings

We conducted a systematic search for patent documents using the publicly accessible database search interface of the German Patent and Trademark Office. We defined keywords and search criteria and developed search patterns for the database request. We retrieved documents with application date between 1988 and 2006 and processed the collected data stepwise to compile the most relevant documents in patent families for further analysis. We developed a rationale and present individual steps of a systematic method to request and process patent data from a publicly accessible database. We retrieved and processed 10194 patent documents. Out of these, we identified 1772 relevant patent families, applied for by 193 different universities and non-university public research organisations. 827 (47%) of these patent families contained granted patents. The number of patent applications submitted by universities and university-affiliated institutions more than tripled since the introduction of legal reforms in 2002, constituting almost half of all patent applications and accounting for most of the post-reform increase. Patenting of most non-university public research organisations remained stable.

Conclusions

We search, process and analyse patent applications from publicly accessible databases. Internationally mounting evidence questions the viability of policies to increase commercial exploitation of publicly funded research results. To evaluate the outcome of research policies a transparent evidence base for public debate is needed in Germany.     

Patent pools and clearinghouses in the life sciences

The biopharmaceutical industry is slowly absorbing the idea of collaborative patent licensing models. Recently, two patent pools for developing countries have been launched: the Pool for Open Innovation against Neglected Tropical Diseases initiated by GlaxoSmithKline (GSK), which is referred to as the BIO Ventures for Global Health (BVGH) pool, and the Medicines Patent Pool (MPP) initiated by UNITAID. Various organizations have recommended using pools or clearinghouses beyond the humanitarian dimension where many patents are owned by many different actors. As a first attempt, MPEG LA, which administers patent pools in various technology fields, is now setting up a clearinghouse for patents related to molecular diagnostics. These examples as well as the results from an empirical study provide useful insights for the design and administration of future pools and clearinghouses in the life sciences.     

Are Patents Impeding Medical Care and Innovation?

Background to the debate: Pharmaceutical and medical device manufacturers argue that the current patent system is crucial for stimulating research and development (R&D), leading to new products that improve medical care. The financial return on their investments that is afforded by patent protection, they claim, is an incentive toward innovation and reinvestment into further R&D. But this view has been challenged in recent years. Many commentators argue that patents are stifling biomedical research, for example by preventing researchers from accessing patented materials or methods they need for their studies. Patents have also been blamed for impeding medical care by raising prices of essential medicines, such as antiretroviral drugs, in poor countries. This debate examines whether and how patents are impeding health care and innovation.     

干细胞专利价值评估与转移转化对策研究 *

Objective: To construct an indicator model for stem cell patent evaluation and to analyze the factors affecting stem cell patent transfer and transformation in real scenarios besides the indicators.Methods:Based on the Patent Value Analysis Indicator System edited by China Technology Exchange, a patent evaluation system suitable for stem cells patents was constructed. The weight was determined by AHP, and the operability of the indicator model was verified by case analysis.Results:Based on the technical characteristics of stem cell technologies and operability, an indicator system for evaluating stem cell patents was constructed, which included three first-level indicators including technical value, market value and legal value, and nine second-level indicators such as technological advancement, technological maturity, technological cost, et al. Technological advancement, technological maturity, policy adaptability and market demand were the four most influential indicators for the valuation of stem cell patents. In the analysis of other factors, the core advantage of the stem cell technologies was the key to affect the transformation of stem cell patents. In addition, technical feasibility, quality control and long-term benefits also had important impact on the successful transfer and transformation of stem cell technologies.Conclusion:The patent value evaluation model and factor analysis established can be used in stem cell patent evaluation, which is helpful to promote the effective development and industrialization of the patent technology.     

KSR Int'l Co. v. Teleflex, Inc.: no obvious changes for the biotechnology market

With the advent of molecular biology, genomics, and proteomics, the intersection between science and law has become increasingly significant. In addition to the ethical and legal concerns surrounding the collection, storage, and use of genomic data, patent disputes for new biotechnologies are quickly becoming part of mainstream business discussions. Under current patent law, new technologies cannot be patented if they are “obvious” changes to an existing patent. The definition of “obvious,” therefore, has a huge impact on determining whether a patent is granted. For example, are modifications to microarray protocols, popular in diagnostic medicine, considered “obvious” improvements of previous products? Also, inventions that are readily apparent now may not have been obvious when discovered. Polymerase chain reaction, or PCR, is now a common component of every biologist’s toolbox and seems like an obvious invention, though it clearly was not in 1983. Thus, there is also a temporal component that complicates the interpretation of an invention’s obviousness. The following article discusses how a recent Supreme Court decision has altered the definition of “obviousness” in patent disputes. By examining how the obviousness standard has changed, the article illuminates how legal definitions that seem wholly unrelated to biology or medicine could still potentially have enormous effects on these fieldsJust what is obvious or not is a question that has provoked substantial litigation in the Federal Circuit, the appellate court with special jurisdiction over patent law disputes. Under U.S. patent law, an inventor may not obtain a patent, which protects his invention from infringement by others, if the differences between the subject matter sought to be patented and the prior art are such that “the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill” in the patent’s subject matter area [1]. However, what was “obvious” at the time of invention to a person of ordinary skill is hardly clear and is, in effect, a legal fiction designed to approximate objectivity. As illustrated by Chief Justice John Roberts of the Supreme Court in a moment of levity, “Who do you get to ... tell you something’s not obvious … the least insightful person you can find?” [2] Despite the apparent objectivity provided by a “person of ordinary skill” obviousness standard, the difficulty lies in that such a standard is still susceptible to multiple interpretations, depending on the point of view and knowledge ascribed to the “ordinary person.” As such, how obviousness is defined and interpreted by the courts will have important implications on biotechnology patents and the biotechnology business.The issue of obviousness arose in April 2007 when the Supreme Court handed down its decision in KSR Int’l Co. v. Teleflex, Inc. [3] The facts of the case were anything but glamorous; in the suit, Teleflex, a manufacturer of adjustable pedal systems for automobiles, sued KSR, its rival, for infringement of its patent, which “describe[d] a mechanism for combining an electronic sensor with an adjustable automobile pedal so that the pedal’s position can be transmitted to a computer that controls the throttle in the vehicle’s engine.” [4] Teleflex believed that KSR’s new pedal design was too similar to its own patented design and therefore infringed upon it [5]. In defense, KSR argued that Teleflex’s patent was merely the obvious combination of two pre-existing elements and, thus, the patent, upon which Teleflex’s infringement claim was based, was invalid.Patent law relies on the concept of obviousness to distinguish whether new inventions are worthy of being protected by a patent. If a new invention is too obvious, it is not granted a patent and is therefore not a legally protected property interest. However, if an invention is deemed not obvious and has met the other patentability requirements, a patent will be granted, thereby conferring exclusive use of the invention to the patent holder. This exclusive right prohibits others from making, using, selling, offering to sell, or importing into the United States the patented invention [6]. Essentially, the definition of obviousness sets the balance between rewarding new inventions with exclusive property rights and respecting old inventions by not treating minor variations of existing patents as new patents. In this manner, the law seeks to provide economic incentives for the creation of new inventions by ensuring that the property right conferred by the patent will be protected against insignificant variations. The importance of where the line for obviousness is drawn and how clearly it is drawn is especially important in the biotechnology industry. Studies have shown that the development of a new pharmaceutical therapy can take up to 14 years with costs exceeding $800 million [7]. Such an enormous investment of time and money would not be practical if it did not predictably result in a legally enforceable property right.The standard for what constitutes a patentable discovery has evolved over the last 150 years. In 1851, the Supreme Court held in Hotchkiss v. Greenwood that a patentable discovery required a level of ingenuity above that possessed by an ordinary person [8]. Lower courts treated the Hotchkiss standard as a subjective standard, whereby courts sought to determine “what constitute[d] an invention” [9] and a “flash of creative genius” [10]. However, the attempts at imposing the Hotchkiss standard proved unworkable, and in 1952, Congress overrode the case law with the Patent Act, “mandat[ing] that patentability be governed by an objective nonobviousness standard.” [11] This new statutory standard moved the courts away from subjective determinations and toward a more workable, objective obviousness standard.While the Patent Act laid the foundation for the current obviousness standard, the Supreme Court in Graham v. John Deere Co. interpreted the statutory language in an attempt to provide greater clarity as to what exactly “obvious” meant [12]. The Supreme Court determined that the objective analysis would require “the scope and content of the prior art ... to be determined; differences between the prior art and the claims at issue ... to be ascertained; and the level of ordinary skill in the pertinent art resolved.” [13] In addition to analysis under this three-part framework, the Supreme Court called for several secondary considerations to be weighed, including “commercial success, long felt but unresolved needs, [and the] failure of others [to solve the problem addressed].” [13]Unsurprisingly, lower courts were unsatisfied with the Supreme Court’s attempts to clarify the obviousness standard and sought to provide “more uniformity and consistency” to their evaluation of obviousness than the Supreme Court’s jumble of factors provided [14]. In search of consistency, the Federal Circuit created the “teaching, suggestion, or motivation” test (TSM test) “under which a patent is only proved obvious if ‘some motivation or suggestion to combine prior art teachings’ can be found in the prior art, the nature of the problem, or the knowledge of a person having ordinary skill in the art.” [14] Through implementation of the TSM test, the Federal Circuit sought to maintain the flexibility envisioned by the Supreme Court in Graham, while at the same time providing more certainty and predictability to obviousness determinations.The issue before the Supreme Court in KSR Int’l Co. v. Teleflex, Inc. was whether the Federal Circuit’s elaboration on the statutory language of the Patent Act, the TSM test, was consistent with the terms of the Patent Act itself and the Supreme Court’s own analysis in Graham. The Supreme Court determined that while the TSM test was, on its terms, consistent with the framework set out in Graham, the rigid manner in which the Federal Circuit had taken to applying that standard was inconsistent with the flexible approach established by Graham [15]. More generally, it appears the Supreme Court was mainly interested in restoring a more rounded, thorough inquiry to the evaluation of obviousness: “Graham set forth a broad inquiry and invited courts, where appropriate, to look at any secondary considerations that would prove instructive.” [16] As stated by the Supreme Court, “[r]igid preventative rules that deny factfinders recourse to common sense, however, are neither necessary under our case law nor consistent with it.” [17] As such, the Supreme Court reversed the findings of the Federal Circuit, which had found the Teleflex patent valid, and remanded the case back to the lower court with directions to analyze, without rigid adherence to the TSM test, whether the Teleflex patent was obvious [18].The Supreme Court’s ruling in KSR Int’l Co. v. Teleflex, Inc. that the Federal Circuit apply its TSM test less rigidly may have implications for those seeking biotechnology patents in the future. As discussed above, the large investments necessary to develop a marketable biotechnology product demand that entrepreneurs making those investments be reasonably assured that they can predict any future legal hurdles in patenting their invention and in ultimately protecting their patent. As explained by the Biotechnology Industry Organization in its amicus curiae brief in KSR Int’l Co. v. Teleflex, Inc., “[i]nvestment thus is predicated on an expected return on investment in the form of products or services that are protected by patents whose validity can be fairly determined.” [19] Therefore, the Supreme Court’s insistence that the Federal Circuit no longer rigidly rely on the TSM test could increase uncertainty in the grant of future patents. However, the Supreme Court’s refusal to completely dismiss the TSM test, while in fact endorsing its continued use, albeit on a less rigid basis, has to be viewed as a profound victory for an industry with a significant stake in maintaining the status quo. Moreover, it is unclear how much the Supreme Court’s holding in KSR Int’l Co. v. Teleflex, Inc. will truly change the legal analysis of the lower courts, given the evidence that lower courts already were independently shifting away from rigid adherence to the TSM test before the Supreme Court’s ruling [20].More importantly, several aspects of the Supreme Court’s reasoning in KSR Int’l Co. v. Teleflex, Inc. seem to directly address relevant concerns of the biotechnology market in favorable ways. First, the Supreme Court made clear that though a product is the result of a combination of elements that were “obvious to try,” it is not necessarily “obvious” under the Patent Act. Retaining the possibility that “obvious to try” inventions still may be patentable is extremely important to the biotechnology industry in particular because “many patentable inventions in biotechnology spring from known components and methodologies found in [the] prior art.” [21] Rather than foreclosing all “obvious to try” inventions as being obvious, and therefore not patentable, the Supreme Court instead explained that where there is “a design need or market pressure to solve a problem and there are a finite number of identified, predictable solutions,” it is more likely that a person of ordinary skill would find it obvious to pursue “known options.” [22] Thus, the proper inquiry, as stated by the Supreme Court, is “whether the improvement is more than the predictable use of prior art elements according to their established functions.” [23] While this reasoning may prevent some “obvious to try” inventions from being patented, it is unlikely to have a substantial effect on inventions in the biotechnology market because “most advances in biotechnology are only won through great effort and expense, and with only a low probability of success in achieving the claimed invention at the outset.” [24] In other words, it would be hard to characterize the use of prior art in the biotechnology context as predictable based on the inherent unpredictability of obtaining favorable results. As such, most biotechnology inventions would presumably fall outside the Supreme Court’s “obvious to try” reasoning due to the very nature of the industry, meaning they would remain patentable under the Supreme Court’s KSR Int’l Co. v. Teleflex, Inc. decision.Second, the Supreme Court recognized the “distortion caused by hindsight bias” and the importance of avoiding “arguments reliant upon ex post reasoning,” though it lessened the Federal Circuit’s rigid protection against hindsight bias [24]. Hindsight bias requires that obviousness be viewed at the time the invention was made, because what may seem revolutionary at the time of invention may, upon the passage of time, seem “obvious.” Cognizance of hindsight bias is crucial for biotechnology patents because “there often is a long ‘passage of time between patent application filing and litigation with biotechnology inventions [that] can exacerbate the problem’ of hindsight bias.” [25] The problem is further exacerbated by the “significantly longer durations of commercial utility” biotechnology inventions enjoy as compared to those in other fields [25]. The more time between the filing of a patent and the subsequent litigation over its validity, the greater the risk that “reliable accounts of [the] context” in which the discovery is made will no longer exist [26]. As such, inventions that were not obvious when they were created will be inescapably colored by the passage of time and by new knowledge and discoveries; the likelihood of this occurrence is higher the further removed the litigation is from the patent filing date. Once again, however, it seems clear that despite the Supreme Court’s abandonment of the TSM test’s rigidity, strong protections against hindsight bias still were emphasized in the Supreme Court’s KSR Int’l Co. v. Teleflex, Inc. decision. In fact, lower courts applying KSR Int’l Co. v. Teleflex, Inc. acknowledge they are “cautious” to avoid “using hindsight” in biotechnology obviousness determinations [27].Finally, the Supreme Court seems to believe that the imposition of a more flexible approach will be more likely to benefit markets not directly at issue in KSR Int’l Co. v. Teleflex, Inc. The Supreme Court asserted, “[t]he diversity of inventive pursuits and of modern technology counsels against limiting the analysis” to the rigid TSM test of the Federal Circuit [28]. This language suggests that the Supreme Court expects lower courts to take into consideration the special considerations facing unique markets, such as the biotechnology market. As such, the specific concerns of the biotechnology market discussed above may receive more attention under the flexible framework asserted by the Supreme Court in KSR Int’l Co. v. Teleflex, Inc.Leading up to the oral argument in KSR Int’l Co. v. Teleflex, Inc., there was widespread speculation that the case could result in a watershed moment, significantly altering the definition of obviousness in patent law. For many, including those in the biotechnology industry, there was ample reason to be concerned. Any change in the definition of obviousness would effectively shift property rights from new patent holders to old, or vice versa. However, the Supreme Court acted with restraint. While the decision purports to make substantial changes by doing away with the Federal Circuit’s TSM test, the opinion seems more like a mild-mannered rebuke of lower courts that had become too complacent in the implementation of their beloved test. If anything, the Supreme Court’s insistence on a more flexible formula is simply a call for lower courts to employ common sense, in addition to considering the factors from Graham and the TSM test. Accordingly, the Supreme Court’s opinion in KSR Int’l Co. v. Teleflex, Inc. is unlikely to have a pronounced effect on the biotechnology market, despite the widespread concern generated before the actual decision was handed down.     

Is Patent “Evergreening” Restricting Access to Medicine/Device Combination Products?

Background

Not all new drug products are truly new. Some are the result of marginal innovation and incremental patenting of existing products, but in such a way that confers no major therapeutic improvement. This phenomenon, pejoratively known as “evergreening”, can allow manufacturers to preserve market exclusivity, but without significantly bettering the standard of care. Other studies speculate that evergreening is especially problematic for medicine/device combination products, because patents on the device component may outlast expired patents on the medicine component, and thereby keep competing, possibly less-expensive generic products off the market.

Materials and Methods

We focused on four common conditions that are often treated by medicine/device product combinations: asthma and chronic obstructive pulmonary disease (COPD), diabetes, and severe allergic reactions. The patent data for a sample of such products (n = 49) for treating these conditions was extracted from the United States Food and Drug Administration’s Orange Book. Additional patent-related data (abstracts, claims, etc) were retrieved using LexisNexis TotalPatent. Comparisons were then made between each product’s device patents and medicine patents.

Results

Unexpired device patents exist for 90 percent of the 49 medicine/device product combinations studied, and were the only sort of unexpired patent for 14 products. Overall, 55 percent of the 235 patents found by our study were device patents. Comparing the last-to-expire device patent to that of the last-to-expire active ingredient patent, the median additional years of patent protection afforded by device patents was 4.7 years (range: 1.3–15.2 years).

Conclusion

Incremental, patentable innovation in devices to extend the overall patent protection of medicine/device product combinations is very common. Whether this constitutes “evergreening” depends on whether these incremental innovations and the years of extra patent protection they confer are proportionately matched by therapeutic improvements in the standard of care, which is highly debatable.     

Opposition to Myriad Genetics patents and their total or partial revocation in Europe: early conclusions

The proceedings instituted against three European patents held by the US company Myriad Genetics, on the BRCA1 gene and the breast cancer diagnosis gene, resulted in the total or partial revocation of these patents. These decisions put an end to the legal monopoly claimed by Myriad Genetics on the BRCA1 gene and on breast cancer gene tests, and left the field open to European geneticists to develop and implement their test methods within the framework of a clinical not-for-profit organization. The opposition procedure, through which any actor is allowed to challenge European patents, was used by geneticists doctors in Europe to refuse the emergence of an industrial monopoly on a medical service offered in a clinical context. The decision to revoke or strongly limit these patents was based on the European Patent Office's refusal to establish an invention priority on a sequence that had errors at the time the application was filed by the patent holder, in September 1994. The patent holder was granted an invention priority only on 24 March 1995, when it filed an application for a corrected sequence of the gene. But by then the BRCA1 gene sequence had already been divulged in a public data base, Genbank, from October 1994, notably by Myriad. Myriad Genetics' patents were thus victims of the patent race that prompted the firm to file multiple patent applications on insufficiently validated sequences, and of the conflict between diffusion in the public domain and the novelty requirement. Opposition to the patents, undertaken by a coalition of medical institutions, human genetic societies, two States, Holland and Austria, an environmental protection organization (Greenpeace), and the Swiss Labour Party, made it possible to preserve and develop the clinical economy of genetic tests in Europe. It resulted in amendments to intellectual property laws in France and thus extended the possibility of using compulsory licences for public health purposes to in vitro diagnosis.