从Myriad案谈基因专利的正当性及美国对基因专利授权实质性要件分析

按照专利制度构建的本质,基因专利的作用在于激励产业创新,促进基因研究的发展。但基因专利从产生以来就一直存在着争议。2011年美国Myriad案对分离DNA序列的可专利性具有不同的观点,从Myriad I案认为分离的DNA是不可专利的客体,到Myriad II上诉案中联邦巡回上诉法院推翻地方法院的观点,认为分离的DNA具有不同的化学结构,满足专利客体的适格性,但同时也反射出了对DNA序列可专利性的怀疑。Myriad案引起了美国、欧洲和澳大利亚司法审判中就基因专利适格性问题的较大争议。本文结合美国Myriad案来分析DNA序列作为专利客体的适格性以及目前美国对基因专利授权的实质性条件。     

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.     

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.     

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.     

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。     

Decoding the research exemption

While debate continues as to whether genetic sequences, which many argue represent natural phenomena rather than inventions, should be subject to standard patent protections, issuance of patents that claim DNA sequences remains common practice. In an attempt to insulate researchers from patent claims that could hinder scientific progress, many countries have provided general exemptions for scientific research. However, there is no international consensus about the extent of required protections, and even existing exemptions vary widely in clarity and are limited in practical application. We believe that gene patents raise several unique issues that are inadequately handled by the current research exemptions.     

A patent landscape on application of microorganisms in construction industry

Construction biotechnology includes research and development of construction materials and processes that make use of various microbes. The present technology landscape gives a perspective on how microbes have been used in construction industry as cement and concrete additives by analyzing patents filed in this technology arena. All patents related to the technology of interest published globally to date have been reviewed. The earliest patent filing in this technology domain was recorded in the year 1958 and the patenting activity reached its peak around mid to late 1990s. The early technology was mainly focused on microbial polysaccharides and other metabolic products as additives. Year 2002 onwards, biomineralization has taken precedence over the other technologies with consistent patent filings indicating a shift in innovation focus. Japan has been the global leader with highest number of patents filed on application of microbes in construction industry. Southeast University, China has topped the patent assignee list with maximum number of filings followed by Kajima Corp. and Shin-Etsu Chemical Co., Ltd. Most patent applications have claimed microbe based bio-products. Construction-related microbial technologies are mainly based on activity of different microorganisms such as urease-producing, acidogenic, halophilic, alkaliphilic, nitrate and iron-reducing bacteria. Sporosarcina pasteurii has been the most widely used microbe for biomineralization.     

Extending the market exclusivity of therapeutic antibodies through dosage patents

Dosage patents are one way to extend the market exclusivity of an approved drug beyond the lifetime of the patent that protects the drug as such. Dosage patents may help to compensate the applicant for the long period where the active pharmaceutical ingredient as such is already under patent prosecution, but not on the market yet, due to lengthy development and approval procedures. This situation erodes part of the time the drug is marketed under patent protection. Dosage patents filed at a later date can provide remedy for this problem. Examples of successful and unsuccesful attempts, and the reasons for the respective outcomes, are provided in this article.     

An Empirical Analysis of Primary and Secondary Pharmaceutical Patents in Chile

We analyze the patent filing strategies of foreign pharmaceutical companies in Chile distinguishing between “primary” (active ingredient) and “secondary” patents (patents on modified compounds, formulations, dosages, particular medical uses, etc.). There is prior evidence that secondary patents are used by pharmaceutical originator companies in the U.S. and Europe to extend patent protection on drugs in length and breadth. Using a novel dataset that comprises all drugs registered in Chile between 1991 and 2010 as well as the corresponding patents and trademarks, we find evidence that foreign originator companies pursue similar strategies in Chile. We find a primary to secondary patents ratio of 1:4 at the drug-level, which is comparable to the available evidence for Europe; most secondary patents are filed over several years following the original primary patent and after the protected active ingredient has obtained market approval in Chile. This points toward effective patent term extensions through secondary patents. Secondary patents dominate “older” therapeutic classes like anti-ulcer and anti-depressants. In contrast, newer areas like anti-virals and anti-neoplastics (anti-cancer) have a much larger share of primary patents.     

Patent searches as a complement to literature searches in the life sciences--a 'how-to' tutorial

This communication provides an easy-to-follow protocol for using the free Internet-accessible scientific search engine, Scirus, to search for and subsequently retrieve published patents from several patent offices in portable document format (PDF). Hints on how to 'read' patents and how to extract relevant information, as well as how to export bibliographic data from Scirus and how to cite patents, are also given. The reason for providing such a protocol is that a vast amount of information, also of potential interest to life scientists, is largely hidden for those not knowing how to access these data. Several examples are provided that highlight the reasons to include patent searches into the workflow of life scientists. These include early access to data before publication, patents as a source of data that never appear in the literature and patents as a source of critical information otherwise hard to get from commercial suppliers. Finally, alternative free patent search services are briefly discussed, and their differences are highlighted.     

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.     

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.     

基于专利信息分析的中国3D生物打印技术发展与产业化研究*

目的:基于专利信息对我国3D生物打印技术的发展态势进行分析。方法:本文基于incopat和TDA两大专利分析平台对中国3D生物打印的专利发展态势从专利统计分析与专利计量分析两个维度进行了跨库组合分析,总结了我国3D生物打印技术的专利前沿动态特征。结果:研究发现,中国3D生物打印技术从2013年起进入专利激增态势,中国作为潜在技术市场的国际竞争日趋激烈,本文还从专利申请人、技术领域分布、专利文本关键词聚类、专利价值、专利合作等方面进行了深度挖掘分析。结论:最后,结合对中国3D生物打印专利申请人的专利产业化案例深度分析与专利特征总结,为中国3D生物打印技术发展与产业化提供参考建议。     

Polymorphs and Prodrugs and Salts (Oh My!): An Empirical Analysis of “Secondary” Pharmaceutical Patents

Background

While there has been much discussion by policymakers and stakeholders about the effects of “secondary patents” on the pharmaceutical industry, there is no empirical evidence on their prevalence or determinants. Characterizing the landscape of secondary patents is important in light of recent court decisions in the U.S. that may make them more difficult to obtain, and for developing countries considering restrictions on secondary patents.

Methodology/Principal Findings

We read the claims of the 1304 Orange Book listed patents on all new molecular entities approved in the U.S. between 1988 and 2005, and coded the patents as including chemical compound claims (claims covering the active molecule itself) and/or one of several types of secondary claims. We distinguish between patents with any secondary claims, and those with only secondary claims and no chemical compound claims (“independent” secondary patents).We find that secondary claims are common in the pharmaceutical industry. We also show that independent secondary patents tend to be filed and issued later than chemical compound patents, and are also more likely to be filed after the drug is approved. When present, independent formulation patents add an average of 6.5 years of patent life (95% C.I.: 5.9 to 7.3 years), independent method of use patents add 7.4 years (95% C.I.: 6.4 to 8.4 years), and independent patents on polymorphs, isomers, prodrug, ester, and/or salt claims add 6.3 years (95% C.I.: 5.3 to 7.3 years). We also provide evidence that late-filed independent secondary patents are more common for higher sales drugs.

Conclusions/Significance

Policies and court decisions affecting secondary patenting are likely to have a significant impact on the pharmaceutical industry. Secondary patents provide substantial additional patent life in the pharmaceutical industry, at least nominally. Evidence that they are also more common for best-selling drugs is consistent with accounts of active “life cycle management” or “evergreening” of patent portfolios in the industry.     

基于国际专利数据的真菌黑色素创新发展趋势分析

【背景】黑色素具有抗肿瘤、抗辐射等多种生物活性,在生产和生活中具有巨大的应用潜力,通过真菌生产是获取黑色素的一条重要途径,它与动植物相比具有更短的生产周期和更高的产量,并且易于实现商业应用。【目的】揭示真菌黑色素的生产及应用发展情况和创新趋势,为致力于真菌黑色素产业的科研人员和企业提供参考。【方法】基于Inco Pat科技创新情报平台,通过对全球真菌黑色素相关专利进行检索统计,从专利涉及的菌株、专利技术构成、申请人专利价值等多维度对真菌黑色素相关专利进行深入分析。【结果】真菌黑色素在生产制备领域申请专利数量最多(50.56%),作为化工染料和化妆品原料应用的专利申请数量最少(13.48%),涉及的真菌菌属主要有层孔菌属、短梗霉属、木耳属、纤孔菌属、粒毛盘菌属、灵芝属和曲霉属。目前真菌黑色素专利技术申请的热点领域主要在C12 (微生物发酵、培养基、突变或遗传工程)类和A61 (医学)类,并且在未来一段时间内,C12和A61将继续作为热点技术申请领域。中国申请的真菌黑色素专利数量最多,但拥有的高价值专利比例较低,较国外仍具有一定差距。【结论】我国科研人员需要加强在医药和化工领域核心专利技术的创新应用与海外布局,增强与企业的合作研发和技术转移,以抢占真菌黑色素在这些领域的应用市场,并推动真菌黑色素相关专利向高质量发展。     

基于专利分析的3D生物打印产业发展态势研究

目的:揭示3D生物打印产业技术研发态势和专利布局,以期为相关机构提供竞争情报,为行业发展提供数据支撑。方法:基于3D生物打印领域产业调研和技术分解,构造检索式获取数据,多维度量化分析领域专利。结果:3D生物打印产业发展可分为孕育期、萌芽期和高速发展期;该产业集中度较低,处于分散竞争阶段;申请人多依据地缘因素选择合作对象,合作方之间多为不同类型的机构;中国申请人的专利申请量占全球的比重已接近50%,但美国申请人的专利篇均被引频次仍远超中国;美国申请人更关注海外市场。结论:3D生物打印产业尚未形成规模效应,有必要整合业内资源,打造产业集群;中、美两国在该产业都具有优势地位,中国亟待加强海外专利布局;综合权衡专利数量和质量,美国申请人的专利竞争力仍高于中国,中国需培育更多核心专利。     

Patenting genome research tools and the law

Patenting genes encoding therapeutic proteins was relatively uncontroversial in the early days of biotechnology. Controversy arose in the era of high-throughput DNA sequencing, when gene patents started to look less like patents on drugs and more like patents on scientific information. Evolving scientific and business strategies for exploiting genomic information raised concerns that patents might slow subsequent research. The trend towards stricter enforcement of the utility and disclosure requirements by the patent offices should help clarify the current confusion.     

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.