Excerpt (section I) from BIOTECHNOLOGY, TECHNOLOGY POLICY, AND PATENTABILITY: NATURAL PRODUCTS AND INVENTION IN THE AMERICAN SYSTEM, by John M. Golden*. Click here for entire article.

* Law clerk for the Honorable Michael Boudin of the United States Court of Appeals for the First Circuit. J.D., Harvard Law School; Ph.D., Harvard University. I thank William W. Fisher III, and Thomas H. Lee for their comments on earlier drafts. I am also grateful for the aid and advice of Mario Biagioli and Douglas Melton. Any errors should, of course, be attributed to me, rather than to those who provided assistance.

SUMMARY:
... What specific environments and individuals produce invention, and what can patent law do to speed inventive progress? The rational construction of patent law demands answers to these questions, particularly in the United States, where the Constitution explicitly gives patent law the purpose of promoting scientific and technological progress. ... Moreover, because the "small company" approach to biotechnology has, at the very least, not prevented the United States from being the world's acknowledged biotechnology leader, a complete overhaul of existing patent law does not currently appear in order, irrespective of concerns about patents' encroachment on the traditional territory of public sector science. ... The biotechnology industry's growth was by no means independent of patent law. ... Consideration of the "small company" model naturally leads to a last, backstop theory of patent protection, one that has been widely accepted within United States policymaking circles but not so triumphantly touted in the patent law literature. ... Consequently, at a time when patents threaten to lay claim to segments of the life sciences' core subject matter, patent law must devise a way to police the public property line - to permit the continued flourishing of public sector science, while still protecting a private domain consistent with a healthfully humbled "small company" theory of biotechnological invention. ...  

 
What is this world? What asketh men to have? n1

TEXT:
 [*101]  Introduction
 
What specific environments and individuals produce invention, and what can patent law do to speed inventive progress? The rational construction of patent law demands answers to these questions, n2 particularly in the United States, where the Constitution explicitly gives patent law the purpose of promoting scientific and technological progress. n3 Nonetheless, legal com-  [*102]  mentators traditionally treat such questions only briefly and superficially, before moving to the more peculiarly "legal" work of analyzing doctrine as established through statutes and case law. n4 Although this tendency may accord with a modest sense of scholarly competence, it cannot, by itself, ensure that patent law sensibly advances its constitutional purpose. Study that confines itself to formal legal materials cannot answer whether patent monopolies, on balance, promote or impede innovation, for such study ignores an institutional and social context that provides independent spurs to innovation, spurs that may already suffice to inspire potentially patentable inventions. Only by studying the broader context of patent law, and - in particular - only by locating patent law within a modern world of both publicly funded and privately funded research, can one hope to identify the optimal balance between motivation and constraint that patent monopolies would ideally provide. Recognizing that the institutional and social context of patent law varies from industry to industry, this Article concentrates on developing an understanding of this context, and its significance for patent law, in one particular industry - that of biotechnology, the industry that seeks to produce marketable products through the manipulation of our and other creatures' genetic codes. n5

As anyone who follows the news can surmise, the choice of biotechnology is not a matter of chance. n6 With the mapping of the human genetic code nearly (and, for many practical purposes, already) complete, the present moment cries out for a study of the wider social and institutional context of biotechnological innovation. The rapid developments in this field do more than challenge the boundaries of patent law. Biotechnological developments hold the very real potential to have a substantial impact on the welfare of almost every human on the planet - a prospect that has led many to proclaim that we have just  [*103]  embarked upon the "biotech century." n7 This sense that we have entered a new age based on the microscopic manipulation of organic matter has stimulated hopes, sometimes bordering on the euphoric, that we can now begin to build a more livable and "living" society from the molecular level on up. Envisioning a world enriched by genetically modified organisms and a new breed of individually targeted therapies, technological optimists see the era of biomolecular engineering as offering an unprecedented capacity to combat human want and disease. n8 For such optimists, the crucial question is how best to speed progress so that biotechnology's bounty becomes most abundantly available in the least possible time.

The optimists do not stand unopposed. Less sanguine individuals warn that biotechnological advances threaten ethical, ecological, or individual disaster. n9 Moreover, governments themselves have begun to struggle with the questions of ethics and privacy that are naturally produced by humanity's newfound ability to probe and control our biological foundations. n10

 [*104]  Nonetheless, although "biotechnology pessimists" have legitimate political claims, it is the optimists' vision that patent law seeks to advance. n11 United States patent law is, under the Constitution, dedicated to "promoting the Progress of Science and useful Arts" n12 - without reference to morality. n13 It is, therefore, the "optimist's question" of how to speed biotechnological advance that concerns patent law, and it is this "optimist's question" that this Article seeks to address. The question is primarily one of policy, rather than abstract principle, n14 and therefore requires attention not only to patent law's developed history, doctrines, and practices, but also to the "inventive" institutions and individuals with which patent law interacts.

Indeed, the importance of attention to context becomes clear once one appreciates that patent law's answer to the "optimist's question" is necessarily a tricky and contingent one, involving a delicate balance between two prongs of social desire: the desire to encourage initial invention and the desire to ensure the availability of that invention both for its initially intended use and for its use as a basis for further invention. Consistent with Congress's constitutional authority to "promote the Progress of Science and useful Arts," n15 patents are meant to provide temporary monopolies that give innovators an  [*105]  incentive "to bring forth new knowledge." n16 However, because patents provide this spur to progress through a monopoly grant, there is an ever-present concern that they will overreach - granting property rights beyond what inventors legally deserve, or (of more fundamental concern) beyond what best promotes the development and dissemination of technological products. n17

In the world of biotechnology, the question whether patent law has overshot its mark is currently a subject of heated debate. For decades, it has been clear that "inventors" can patent purified versions of naturally occurring organic molecules, n18 as well as purified strains of living organisms. n19 Now, however, with private companies rushing to patent fragments of deoxyribonucleic acid ("DNA"), n20 patent office officials, n21 scientists, n22 outside  [*106]  commentators, n23 and even heads of state n24 have worried that patent law may be protecting too much. Nevertheless, a consensus that patent protection is the lifeblood of modern biotechnology remains strong, n25 and representatives of biotechnology firms are generally undaunted in their assertions that patent protection, and even stronger or more widely available patent protection, is necessary for them to bring biotechnology products to the market. n26

 [*107]  There is, no doubt, substantial interest in ensuring that the biotechnology industry can do its job. The United States is the world leader in both the production and consumption of biotechnology n27 and is already reaping the benefits of its technological leadership. The United States' biotechnology industry generated $ 18.6 billion in revenues in 1999, n28 and in the past decade President Clinton made clear his conviction that the industry was important for its capacity to create "high-wage American jobs." n29 Of course, the industry is also valuable for its ability to produce life-saving products. On this "life-saving" front, the biotechnology industry already has provided the means for diagnosing susceptibility to a variety of diseases, n30 has produced several hundred-million-dollar-a-year drugs, n31 and has developed hundreds of ad-ditional drugs currently in clinical trials. n32

Given the obvious benefits, both present and potential, of a thriving biotechnology industry, there is a natural conflict between the desire to protect this American success story and the sense that the industrial protagonists of this story advocate more protection than serves the public interest.  [*108]  Consequently, in the realm of biotechnology, United States patent law faces a series of difficult questions. Is the current allowance for the patenting of "purified" or "isolated" versions of naturally occurring substances ill-considered? Does the current scope of patentability threaten to inhibit rather than to promote further advances in biotechnology? If current patent pro-tection goes too far, should we limit it through categorical rules against patenting certain types of substances, or should we instead limit it through stricter enforcement of the more technical standards for patentability (novelty, nonobviousness, and utility)? Alternatively, should patent law instead try to limit patents' effects by construing their scope narrowly or by making greater allowances for non-infringing use? Finally, if patent law cannot achieve the ideal balance between the incentives for invention and dissemination, should Congress provide biotechnology with a special regime of protection, analogous to that created by the Plant Patent Act of 1930 n33 or the Plant Variety Protection Act of 1970? n34

These questions are fundamentally questions of policy, of the "law in action." n35 Consistent with patent law's utilitarian calculus, they necessarily center on practical questions of effectiveness and efficiency, questions of what people do and why they do it. It naturally follows that study of the ambitions and work environments of those who make and fund innovation is necessary to know whether patent law is well designed to promote science and technological progress. Thus, this Article embraces, and seeks by example to support, the thesis that to arrive at a truly informed understanding of the effectiveness of patent law, one must know not only what the law is and could be, but also upon what and whom the law acts.

A primary point to recognize is that proper patent policy is inseparable from effective technology policy. To date, legal studies of patent law have given this point routine, but usually no more than perfunctory, recognition. Legal commentators have frequently acknowledged the obvious fact that patent law looks to promote innovation and industry. n36 However, they have routinely  [*109]  neglected to study the wide variety of mechanisms, outside of patent law and the general money economy, that society uses to stimulate invention. In particular, they have largely ignored the details of the multi-billion dollar system of investment, mostly public and mostly university-based, that provides most of the researchers and basic research that drives modern biotechnology. Even when legal commentators have recognized a conflict between the ideals of a monopoly-seeking market-based economy and a credit-seeking university-based economy, n37 they have still failed to give more than only the barest outlines of the institutional settings in which patent policy operates. This omission needs to be corrected. Without devoting attention to the details of who supports innovation and who forms biotechnology's "inventor class," prior work has left patent law's social utility arguments unanchored, and therefore vulnerable to guesswork or an arbitrary choice of platitudes.

This Article seeks to begin the task of filling in the details of the nature of the biotechnology enterprise as a scientific, governmental, and industrial whole. In short, it seeks to anchor the study of biotechnology patent law in an understanding of the totality of "the American system of innovation." n38 To that end, this Article examines the roles of each of the major players in  [*110]  American biotechnology: the federal government, private investors and industry, the university, n39 and scientific researchers themselves. What is discovered is that, while American industry plays a crucial role in turning inventions into marketable products, publicly funded research still plays a dominant role in fostering the basic scientific and technological advances that drive biotechnology forward. Moreover, this Article suggests that, even in the present age of "entrepreneurial science" n40 and even within industry itself, the values and incentives that motivate biotechnology researchers tend to be closer to the "public sector values" associated with university-based science than to the values associated with a market-oriented focus on maximum financial profit.

What do the background dominance of publicly funded research and public sector values tell us about the foreground issues of patent law? Most fundamentally, they tell us that current concerns about the possible over-extension of American patent law are justified. By extending its reach to subject matter traditionally reserved for the public domain of natural science, patent law risks creating obstacles to future research and invention without adding proportionately to the actual motivations of those who do the inventing. Furthermore, over-emphasis on patent protection risks displacing a system of public sector values that appears to have served science and society well. Continued pressure to extend patent law's money economy at the expense of science's traditional economy of reputational credit could create impediments to future progress while providing less effective, or at least insufficiently effective, countervailing rewards. An understanding of the social and institutional context that produces biotechnology makes real the concern that excessive patent protection could slow, rather than speed, the rate of biotechnological development. In sum, a biotechnology optimist and a "biotechnology patent optimist" are different classes of creatures.

This is not to say that biotechnology patent optimists do not have a case. The conclusion that patent law may impede innovation must be balanced by an understanding of how it can and does facilitate it. This Article shows that, at  [*111]  the level of basic biotechnology, patent law facilitates innovation not so much by "spurring" invention as by "enabling" it, by providing small biotechnology firms, which are the heart of the American biotechnology industry, with an intermediate "product" - patents - that they can use to attract investment. Moreover, because the "small company" approach to biotechnology has, at the very least, not prevented the United States from being the world's acknowledged biotechnology leader, a complete overhaul of existing patent law does not currently appear in order, irrespective of concerns about patents' encroachment on the traditional territory of public sector science.

Nonetheless, this Article eschews a "no holds barred" or even a "stand pat" position with regard to the continued expansion of patent law's reach. Because the concerns about patent law's encroachment on public sector science are rooted in reality, and because the "small company" model itself presumes a vibrant environment of university-based research, this Article argues for stricter enforcement of the basic hurdles to patentability - novelty, non-obviousness, and especially utility - as the best way to serve patent law's "optimistic" goal. Would-be "victors" in the race for biotechnology patents must, at least to some limited extent, be saved from themselves, lest their legal triumphs close off routes to further innovation that could enrich themselves and society.

The structure of this Article is as follows. Part I provides an introduction to American biotechnology, technology policy, and patent law. Part I.A chronicles the growth of American biotechnology from its beginnings in the 1970s. Part I.B then traces concurrent developments in American technology policy, which from the 1970s on increasingly embraced a "cooperative model" of research and development that linked government, university, and industry. Finally, Part I.C follows these histories of technology and technology policy with a "doctrinal review" of United States patent law. This review provides a detailed description and analysis of the recent history and current status of the doctrinal rules that determine the patentability of biotechnology's most characteristic products: artificially modified organisms or cultures, and purified organic molecules.

Building upon the background provided by Part I's discussion of the science, policy, and law of biotechnology, Part II presents a current account of the American biotechnology enterprise. Part II.A analyzes the nature and size of both public and private investment in biotechnology, placing emphasis on the substantial role of publicly funded research in advancing basic science and  [*112]  stimulating the conversion of that science to commercial applications. Part II.B follows with a detailed account of the motivations and milieu of biotechnology's characteristic "inventors" - the thousands of doctorate-holding researchers upon whose ingenuity and diligence biotechnological advance depends. The combination of Part II.A's "money trail" and Part II.B's "motivation analysis" leads to the conclusion that public sector research and values remain a primary and necessary ingredient of the American biotechnology industry's remarkable success.

Part III builds on this conclusion by examining how Part II's understanding of the biotechnology enterprise can inform patent policy in practice. In light of Part II's conclusions, Part III.A rejects the most common legal justifications for patent protection and finds that the theory that best supports strong biotechnology patents is one of "investment attraction." This "small company" or "resources for innovation" theory of patent protection justifies patents as a way to create "intermediate products" that allow biotechnology companies and their investors to "cash in" before completion of the typically long and treacherous path to a viable commercial product. As Part III.A points out, however, the theory is limited, and cannot provide a general defense to charges of patent-monopoly overreach.

Given the "small company" model's limitations and the strong evidence that patent-monopoly overreach is a present or imminent reality, Part III.B explores how patent law can best be brought into line with the "small company" theory's limited warrant. Part III.B argues that, given the continuing success of the American biotechnology enterprise, a complete overhaul of the system for protecting biotechnological invention is neither necessary nor justified. Nevertheless, to ensure that the biotechnology industry's success continues, existing patent law doctrines, and in particular the utility requirement for patentability, must be carefully construed and enforced. In particular, the Patent and Trademark Office ("PTO") and courts should use the utility requirement to impose real, albeit not insurmountable, obstacles to the patenting of genetic sequences. In line with this determination, the Conclusion emphasizes the importance of developing a flexible but firm way of policing the limits of patentability.

 [*113] 

I. Biotechnology, Technology Policy, and Patent Law in the Twentieth Century's Last Quarter
 
The enterprise of American biotechnology is the product of a confluence of developments in the last quarter of the twentieth century - developments in science and industry, government policy, and patent law. Most fundamental to the birth of the biotechnology enterprise was the invention of modern genetic engineering in the early 1970s. This scientific invention made possible a new industry that promised to use cutting-edge science to produce a new generation of diagnostic techniques, treatments, and cures. Entering where opportunity had knocked, a host of small biotechnology firms began springing up around research universities. While these new firms appeared and developed, the federal government was busy re-evaluating its approach to the promotion of science and technology. Not entirely coincidentally, the government's eventual shift to a "cooperative model" of academic, industrial, and federal research fit the needs and mindset of the biotechnology industry almost perfectly, and helped spur the biotechnology boom of the 1980s. Patent law itself showed a similarly propitious ability to serve the biotechnology industry's needs. Under the influence of a new federal appellate court and a series of legislative initiatives, patent law moved with the spirit of the day, producing doctrines and policies sufficiently "modern" to provide enforceable property rights in a substantial share of the purified natural substances that were biotechnology's most characteristic products. n41

A. The Emergence of Genetic Engineering and the Biotechnology Industry
 
As a prelude to discussing how government policy and patent law have combined to promote the biotechnology industry, it is necessary to describe that industry's subject matter and structure. Biotechnology consists of the products and processes of isolating, preparing, and replicating fragments of deoxyribonucleic acid ("DNA") and ribonucleic acid ("RNA"), and using these DNA and RNA fragments to produce proteins, n42 the molecules that, among  [*114]  other things, regulate the various chemical and physical processes that comprise the biological phenomenon of "life." n43 DNA and RNA are the two basic kinds of molecules that carry the genetic code, a series of chemical "letters" that, in sequences called genes, n44 provide cells with the instructions for building proteins. n45 In the 1970s, scientists developed recombinant DNA techniques, in which a fragment of DNA from one cell (for example, that of a human) is inserted into the genetic sequence of another host cell (for example, a bacterium) and then activated so that the host begins to produce the corresponding protein. n46 Recombinant DNA thus allows for the deliberate genetic modification of individual organisms, and, if the host cell reproduces rapidly enough, provides a potential source for mass quantities of the proteins that are the biologically active constituents of many modern medications. n47

Historically, much of the difficulty in using recombinant DNA techniques has consisted in locating, isolating, and sequencing (reading off the successive  [*115]  "letters" of) the genes associated with particular proteins. n48 However, advances in technology and in laboratory techniques have eased and automated much of this process, substantially routinizing a variety of tasks that had previously required considerable effort and ingenuity. n49 Indeed, automation has made possible sequencing the DNA of whole species: n50 researchers using automated sequencers have already sequenced the genomes of a number of small species, n51 and the sequencing of others has become only a matter of attention and time. n52 The Human Genome Project ("HGP"), a thirteen-year international effort n53 backed by public funds, n54 promises to sequence the entire human genome and to catalog all its estimated 100,000 genes by the end of 2003. n55 In the meantime, the HGP and Celera Genomics, a privately funded company, have already announced completion of "rough drafts" of most of the  [*116]  genome. n56 With sequencing reduced to routine and with the results of the HGP and other public sector genome projects n57 being placed in information repositories freely accessible via the internet, n58 it is expected that the next several years will witness a shift in the focus of genetics research toward the more inherently intractable problems of understanding gene and protein function, n59 problems expected to occupy biotechnology researchers for decades to come. n60

Meanwhile, an ever-growing industry of about 1,300 firms specializing in biotechnology n61 seeks to capitalize on the field's obvious practical potential. Biotechnology firms began springing up soon after the development of biotechnology itself - particularly around prestigious universities in New England and the San Francisco Bay Area. n62 The firms' proximity to major centers of publicly funded research has not been accidental. Scientists from major universities have played a crucial role in providing such firms with energy, expertise, and (for the benefit of potential investors) scientific legitimacy. n63 Research scientists have participated in founding most bio-  [*117]  technology firms. n64 Even when not among the founders, present or former university researchers have been pervasive in their presence - as employees, consultants, or members of firms' scientific advisory boards. n65 Moreover, the "presence" of publicly funded research goes beyond the mere provision of people and names. The fact that 71.6% of citations to research papers in biotechnology patents are to publicly funded research n66 gives one measure of the extent to which bio-technology firms depend on continued close relations with the university. n67 The fact that university patents have historically accounted for one tenth to one fifth of the patents in biotechnology-related fields provides another. n68 There is little cause to dispute the characterization of biotechnology as one of a few distinctively "science-based industries." n69

In fact, the biotechnology industry is distinctive not only for its scientific basis but also for its small-firm structure. In marked contrast with most research universities and pharmaceutical companies, biotechnology firms are mostly young, n70 small, n71 and privately held. n72 Although some successful firms  [*118]  have developed profitable product lines, n73 the typical small biotechnology company has little prospect of producing a commercial product in the immediate future. The road to developing a marketable new drug is long and costly, typically requiring five to ten years and at least a few hundred million dollars. n74 Partly because of these long development times, biotechnology firms tend to live on the margins of insolvency. Indeed, it is generally accepted that most such firms will fail. n75 Frequently, their primary assets are knowledge, ideas, trained personnel, and patents. n76 Before they develop a commercial product, they naturally seek financing through joint development projects with larger firms such as pharmaceutical companies, in which they trade intellectual property and technical expertise for cash and business savvy. n77 The resulting  [*119]  "cooperative" structure of the biotechnology industry is well documented: in the mid-1990s, 81.8% of United States biotechnology companies had a drug company research partner, n78 70.5% had a university research partner, 50% had a fellow biotechnology research partner, and 47.7% had a research institute research partner. n79 As the pervasiveness of university alliances indicates, small firms' desperate need to have the best available technology and personnel all but ensures continued strong ties to the knowledge-breeding grounds of the university.

B. The Rise of the Government-Technology Complex
 
Probably not entirely by chance, the development of modern biotechnology in the 1970s and 1980s coincided with a shift toward a "cooperative model" of research and development. This model extols continual interactions between academia and industry, and between different players in industry, as the surest route to expedite technological progress without the need for additional government expenditure. n80 Adoption of this "cooperative model" entailed a substantial abandonment of a traditional post-World War II model for innovation, in which information was viewed as flowing on a predominantly one-way street - from basic research to applied research to commercial development. n81 By emphasizing the need for a more equal to-and-fro between industrial development and academic research, the new model to some extent denied the primacy of basic research, n82 but more affirmatively, emphasized the desirability of lowering the barriers to cross-fertilization between "science" and "technology," each being best understood as existing in a symbiotic relation with the other. n83

 [*120]  The shift toward this "cooperative model" resulted largely from a sense, in the 1970s and early 1980s, that the United States was losing its technological edge n84 and was forfeiting to foreign "free riders" commercial profits derived from the fruits of American investment in basic and applied research. n85 Perturbed policymakers responded with a series of congressional acts and executive actions that sought not only to increase American inventors' capacity to keep their ideas under American control, but also to increase the capacity of, and incentives for, American scientists to assist in the first stages of converting their discoveries to commercial use. n86 Two acts that Congress passed in 1980, the Stevenson-Wydler Act n87 and the Bayh-Dole Act, n88 formed the foundations of the new approach of actively encouraging research collaborations between government laboratories, universities, and industry. n89 The Stevenson-Wydler Act directly endorsed the cooperative model by requiring federal laboratories to facilitate technology transfer to private industry. n90 The Bayh-Dole Act, in turn, sought to stimulate such technology transfer by allowing government grantees and contractors to patent inventions and to sell exclusive licenses for their use. n91 In so doing, the Bayh-Dole Act epitomized the newfound con-fidence in strong intellectual property rights as the route to quick and cheap commercialization. n92

 [*121]  Later acts and executive actions of the 1980s and 1990s elaborated on the approaches of the Stevenson-Wydler and Bayh-Dole Acts. The Trademark Clarification Act of 1984 n93 and Federal Technology Transfer Act of 1986 n94 gave broader technology transfer authority to government-owned, contractor-operated laboratories, and permitted government-owned, government-operated laboratories both to enter Cooperative Research and Development Agreements ("CRADAs") with non-federal entities and to require that federal employees receive a fraction of patent royalties. n95 Subsequent acts reduced the risk of antitrust prosecution for firms performing collaborative research, n96 provided for direct government funding of innovative small businesses, n97 gave further incentives for government actors to enter CRADAs with industry, n98 and fortified statutory protection of intellectual property rights. n99 At the same time that Congress was producing such legislation, the Reagan and Bush administrations relaxed enforcement of the antitrust laws and initiated such  [*122]  government-industry joint ventures as the semiconductor research consortium. n100

Significant sectors of private industry have acted in accord with these government initiatives. Having abandoned the model of large corporate laboratories engaged in basic research, private companies have tended increasingly to meet their research needs through "research joint ventures" and "strategic alliances" with other firms, and through collaborative relationships with university laboratories. n101 Biotechnology has proven to be a particularly fruitful field for such collaboration, n102 both because of bigger firms' interest in diffusing the risks of biotechnology investment among a variety of small firms, n103 and because of the field's comparatively well-established (and perhaps inherent) integration of science and technology. n104 Indeed, the biotechnology industry - dominated by small, young firms that rely for their continued existence on a complex network of collaborative research relationships n105 - emerged in the 1990s as perhaps the leading exemplar of the cooperative approach to innovation through "entrepreneurial science." n106

C. Patent Doctrine in the Age of Biotechnology
 
The biotechnology industry's growth was by no means independent of patent law. After all, for any conception of "entrepreneurial science" to flourish, it requires something to sell. As remarked above, patent law--in particular, 101 of the Patent Act n107 - provides young biotechnology firms  [*123]  with one of their few "assets" - saleable intellectual property rights in some of the most fundamental constituents of life. Prior to 1980, it was not clear that patent law would be so accommodating. In addition to meeting the traditional requirements of novelty, n108 utility, n109 nonobviousness, n110 and enablement, n111 an application for a patent must show that the claimed invention is patentable subject matter. n112 Under 101, patentable subject matter consists of a "process, machine, manufacture, or composition of matter," n113 categories that courts have traditionally held to exclude "products of nature." n114 The Court of  [*124]  Customs and Patent Appeals suggested as late as 1974 that a new strain of microorganisms isolated from a soil sample was an unpatentable natural product, n115 and Congress's passage of the Plant Variety Protection Act in 1970 indicated, at the very least, that the national legislature worried that 101 did not permit the patenting of living things. n116

Nonetheless, in 1980, the Supreme Court substantially alleviated fears that 101 was too doctrinally rigid to accommodate the biotechnology industry's desire to patent its cellular and molecular products. n117 In its decision in Diamond v. Chakrabarty, the Court for the first time, and by a bare majority of five Justices, recognized 101 patentability for "nonnaturally occurring" living things. n118 Moreover, the Court stated a rule of construction likely to produce even broader lower court endorsements of biotechnology patents. According to the Court, Congress intended that allowances for patentability be construed expansively: courts "should not read into the patent laws limitations and conditions which the legislature has not expressed." n119 Although the Court did reaffirm the unpatentability of "the laws of nature, physical phenomena,  [*125]  and abstract ideas," n120 its decision cleared the way for broad patent protection of biotechnology's most characteristic products - genetically modified organisms and purified (and sometimes slightly modified) natural proteins.

The patentability of the latter might have seemed questionable if Chakrabarty had stood alone as an interpretation of modern patent law. However, courts had long since determined that new molecules n121 and, in general, artificial variants of naturally occurring substances are patentable. n122 Furthermore, significantly more purified versions of naturally occurring or known substances had been recognized as patentable "variants" of otherwise natural or known products - at least so long as the difference in purity sufficed to render the product "for every practical purpose a new thing." n123 In 1979, the Court of Customs and Patent Appeals had extended this "greater purity" rationale to biological products, endorsing the view that a particular pure bacterial culture was a "product of a microbiologist," rather than a product of nature. n124

Thus, with the Supreme Court's decision in Chakrabarty, the stage was set for a decade of aggressive expansion of biotechnology patenting. Led by the new Court of Appeals for the Federal Circuit, n125 lower federal courts did not block a zeitgeist that led to a fivefold increase in worldwide biotechnology patenting from 1980 to 1990. n126 Indeed, commentators have generally credited the Federal Circuit with helping to weaken the force of such requirements for  [*126]  patentability as utility and nonobviousness, n127 as well as with helping to allow patents for ever wider ranges of subject matter. n128 Between these doctrinal relaxations and the Federal Circuit's statistical tendency to affirm patent validity, n129 there was reason to believe that Judge Rich, a charter member of the Federal Circuit, captured the court's spirit by responding to concerns about patents' widening reach with the succinct statement, "The more the better." n130

Indeed, whether as a result of a pro-patent judiciary or as a consequence of the natural extension of prior legal doctrine, by the early 1990s patent law had resolved many fundamental issues in favor of biotechnology's patentability. n131  [*127]  Consequently, it is now clear that living matter or organic molecules are patentable if they are distinguishable from naturally occurring organisms or substances and if they meet the traditional requirements of utility, novelty, nonobviousness, and enablement. Moreover, as the Federal Circuit made clear in Amgen, Inc. v. Chugai Pharmaceutical Co., n132 purified and isolated DNA sequences are no exception: DNA's status as "the prime molecule of life" n133 gives it no immunity from the normal rules of patent law. n134 Furthermore, consistent with the sense of Chakrabarty, it is clear that inventors can obtain patents for genetically modified macroscopic plants as well as for genetically modified microorganisms. n135 They can also obtain patents on genetically modified multicellular animals n136 - albeit perhaps with greater difficulty. n137

The question that remains is how much traction traditional requirements for patentability retain. With regard to the "product of nature," novelty, and enablement doctrines, the answer is, practically speaking, "Not much." The "product of nature" doctrine, although still extant, is effectively toothless, because biotechnology by nature involves isolating and replicating biological materials to produce "unnatural" levels of purity. n138 Thus, with respect to  [*128]  biotechnology, the century-old "purification exception" tends to swallow the rule.

The novelty and enablement doctrines are similarly unconstraining. Once a product is shown to be "non-natural," the novelty requirement imposes no more than its usual bite, with the characteristics of originality and priority being ones that biotechnological inventions, considered as a class, easily possess. n139 Likewise, although the enablement requirement does place significant constraints on inventor "behavior," n140 it does little to regulate the patentability of biotechnology per se, unless used as a cover for enforcing the requirement of utility. Instead, by preventing overbroad or ill-described claims, the enablement requirement primarily serves only to narrow the scope of individual patents and to enforce the monopoly-for-disclosure bargain that patent law traditionally requires. n141

Thus, with regard to the patenting of biotechnological subject matter, the real questions that remain at the start of the new century concern the standards for utility and nonobviousness. In recent decades, courts have tended to construe the utility requirement loosely, proclaiming the requirement satisfied by "evidence of any practical utility." n142 Indeed, the requirement has often been described as only demanding that a claimed invention be minimally adept  [*129]  at doing what the patent application says it does. n143 However, the Supreme Court's 1996 decision in Brenner v. Manson n144 remains the leading case on the meaning of "utility." Moreover, its holding that a process is not "useful" merely because it "produces a compound whose potential usefulness is under investigation by serious scientific researchers" n145 could provide a meaningful utility backstop for a patent system that currently faces a flood of DNA sequence claims. Brenner's demand that a patentable invention provide a "currently available" and "specific" benefit n146 could be used to block patents for DNA sequences for which "practical utilities" are more posited than proven - a description that might apply to most existing DNA patent claims. n147

Furthermore, the prospect of meaningful application of the Brenner standard is no pipe dream. The standard has had sporadic force in post-1980 legal practice. The Federal Circuit has itself enforced Brenner's utility requirement on occasion. n148 Perhaps most significantly, the PTO's new guidelines respond to concerns about DNA patents by specifically invoking Brenner as part of a reaffirmation of the need for either "well-established" or "specific and substantial" utility. n149 Thus, although the utility requirement may frequently seem to do no more than bare its teeth, it at least still appears to have teeth, and therefore retains the potential to be a significant barrier to the patentability of biotechnology.

In the abstract, the demand for nonobviousness would seem to have even greater potential to act as a hurdle to biotechnology patentability. However, judicial formulations of the requirement have made it hard to make arguments  [*130]  of nonobviousness stick with regard to biotechnological invention. n150 The courts have settled on a standard that finds an invention obvious only when the prior art sufficed not only to motivate the inventive understanding, but also to enable n151 one skilled in the art to pursue the invention with a "reasonable expectation of success." n152 Moreover, even if the prior art provided the required motivation and enablement, an invention is still nonobvious if it exhibits "unexpected properties." n153 Given the general unpredictability of bio-technological invention n154 and the fact that such invention, when it does occur, often results from sifting through a great variety of individually unlikely possibilities, n155 it is no wonder that nonobviousness has proven difficult to enforce. Furthermore, because the standard revolves around whether the invention was "obvious at the time the invention was made[,] to a person having ordinary skill in the [relevant] art," n156 it is inherently hard for judges and patent examiners to apply the standard sensibly in a rapidly developing field. n157 It is comparatively easy to yield to the zeitgeist and acknowledge the patentability of yet another biotechnology invention. n158

To summarize, what might have seemed to be entrenched doctrines of patent law prior to 1980 have shown remarkable flexibility in the face of the  [*131]  biotechnology industry's craving for expansive intellectual property rights. The patentability of most basic biotechnological products is now well established, and supposedly central requirements such as utility and nonobviousness have often merely nibbled at the margins of patentability's broad realm. Nevertheless, the PTO's new guidelines, and analysis of patent law's relevant doctrine, suggest that the utility requirement may, at least, provide the basis for something more than "nibbling." The purpose of Part II is to try to help us understand why "something more" is desirable.


FOOTNOTES

• n1. Geoffrey Chaucer, The Canterbury Tales, in 1 The Riverside Chaucer 2777, at 62 (Larry D. Benson ed., 3d ed. 1987) (from Arcite's dying statements in The Knight's Tale).

• n2. Although Professor Merges has argued that the indicated answers are irrelevant to the justification of the patent system as a whole, he does acknowledge that they can be significant for developing standards of patentability that best advance net social welfare. See Robert P. Merges, Uncertainty and the Standard of Patentability, 7 High Tech. L.J. 1, 9-10 (1992).
• n3. See U.S. Const. art. I, 8, cl. 8 (giving Congress the power to grant patents "to promote the Progress of Science and useful Arts"); Diamond v. Chakrabarty, 447 U.S. 303, 315 (1980) ("The subject-matter provisions of the patent law have been cast in broad terms to fulfill the constitutional and statutory goal of promoting "the Progress of Science and the useful Arts' with all that means for the social and economic benefits envisioned by Jefferson."). The Federal Circuit has not shied from asserting that patent law imposes a continuing duty to adapt doctrine and practice to speed technology's advance. See Pioneer Hi-Bred Int'l, Inc. v. J.E.M. AG Supply, Inc., 200 F.3d 1374, 1376 (Fed. Cir. 2000) ("Although there remain the traditional categories that have never been viewed as patentable subject matter, viz., laws of nature, natural phenomena, and abstract ideas, the policy underlying the patent system fosters its application to all areas of technology-based commerce."); In re Lundak, 773 F.2d 1216, 1220 n.1 (Fed. Cir. 1985) ("The [Patent and Trademark Office] must continue to adapt its procedures to facilitate the advance of science and technology."). In a recent article, Professors Merges and Reynolds carry this assertion to its logical limit, arguing that the Constitution's stated purposes for intellectual property protection might be used to impose restraints on patent and copyright protection. See Robert Patrick Merges & Glenn Harlan Reynolds, The Proper Scope of the Copyright and Patent Power, 37 Harv. J. on Legis. 45, 46 (2000).
• n4. See Robert P. Merges & Richard R. Nelson, On the Complex Economics of Patent Scope, 90 Colum. L. Rev. 839, 880 (1990) (observing that "while most analyses of the effects of the patent system on invention assume implicitly that technical advance proceeds similarly in all industries, this assumption is mistaken").
• n5. More precisely, this Article focuses on patent law in the field of non-agricultural biotechnology. Partly because of a different set of statutory protections available for genetically modified plants, see infra note 107, but mainly because the agricultural biotechnology industry has a significantly different institutional structure, see infra note 389 and accompanying text, the study of intellectual property protection for "plant biotech" is outside the scope of this work.
• n6. See, e.g., Carol Ezzell, The Business of the Human Genome, Sci. Am., July 2000, at 48 (cover story); Frederic Golden & Michael D. Lemonick, The Race Is Over, Time, July 3, 2000, at 19 (cover story on the mapping of the human genome); A Survey of the Human Genome, Economist, July 1-7, 2000, at 3 (cover story featured in a special insert).
• n7. See, e.g., Jeremy Rifkin, The Biotech Century: Harnessing the Gene and Remaking the World (1998); Kenneth I. Shine, Welcome, in National Research Council, U.S. Dep't of Energy, Serving Science and Society in the New Millennium 1, 1 (1998) (proclaiming that, whereas "the 20th century will be known as the century of physics and astronomy," "the 21st century will be the century of the life sciences in all their ramifications").
• n8. See, e.g., Biotech's Benefits, Boston Globe, Mar. 26, 2000, at E6; Geoffrey Cowley & Anne Underwood, A Revolution in Medicine, Newsweek, Apr. 10, 2000, at 58; Michael D. Lemonick, Brave New Pharmacy, Time, Jan. 15, 2001, at 58, 60; Michael D. Lemonick, The Genome Is Mapped. Now What?, Time, July 3, 2000, at 24; David Stipp, Blessings from the Book of Life: Decoding the Human Genome Will Yield a Bounty of Biotech Miracles That Will Transform Our Lives in the Next 40 Years, Fortune, Mar. 6, 2000, at F-21; Marc Wortman, Medicine Gets Personal, Tech. Rev., Jan./Feb. 2001, at 72, 73-78.
• n9. See Patricia A. Lacy, Comment, Gene Patenting: Universal Heritage vs. Reward for Human Effort, 77 Or. L. Rev. 783, 783 (1998) (noting special privacy concerns with respect to genetic knowledge); Carrie F. Walter, Note, Beyond the Harvard Mouse: Current Patent Practice and the Necessity of Clear Guidelines in Biotechnology Patent Law, 73 Ind. L.J. 1025, 1025 (1998) (recounting ethical and religious concerns, as well as concerns about the potential catastrophic effects of genetically modified organisms on health and the environment); Sharon Begley, Decoding the Human Body, Newsweek, Apr. 10, 2000, at 50, 55-57 (reporting moral concerns about the use of genetic knowledge to discriminate against and to "re-engineer" human beings); Raphael Lewis & Jamal E. Watson, Biotech Protest Draws 2,500, Boston Globe, Mar. 27, 2000, at B1 (reporting various moral and ethical concerns that motivated protestors); Thomas D. Mays, Biotech Incites Outcry: Public Policy Debates Arise over Human-Animal Hybrid Patents and Germline Therapy, Nat. L.J., June 22, 1998, at C1 (describing outrage and fear provoked by the patenting of living beings); J. Madeleine Nash, Grains of Hope, Time, July 31, 2000, at 38 (discussing the controversy over genetically modified foods).
• n10. See, e.g., Michael Balter, France Rebels Against Gene-Patenting Law, 288 Science 2115, 2115 (2000); Raja Mishra, Mass. Poised to OK Genetic Privacy Bill: Measure Would Ban Discrimination, Boston Globe, Aug. 3, 2000, at A1.
• n11. The "pessimist's question" concerns how best to regulate biotechnological advance, whether by channeling or slowing it, to ensure that it does not lead to an episode of humanity playing God badly. Such issues are generally recognized to be beyond the scope of existing United States patent law, at least as interpreted by the Patent and Trademark Office ("PTO") and the courts. See Diamond v. Chakrabarty, 447 U.S. 303, 317 (1980) (describing such issues as "matters of high policy for resolution within the legislative process"). However, Congress has responded to pessimistic concerns in the past, barring patents for inventions that are useful solely to help create atomic weapons, see 42 U.S.C. 2181(a) (1994), and providing that the federal government can withhold patents for reasons of national security, see The Invention Secrecy Act, 35 U.S.C. 181-188 (1994).
• n12. U.S. Const. art. I, 8, cl. 8.
• n13. The especially "utilitarian" tilt of United States patent law is generally recognized. See, e.g., Robert P. Merges et al., Intellectual Property in the New Technological Age 23 (1997) ("Patent law is the classic example of an intellectual property regime modeled on the utilitarian framework."). Because of the acknowledged utilitarianism of United States patent law, this Article does not consider how patent law might be shaped in conformity with other prominent theories of intellectual property theory, such as those emphasizing natural rights to the products of one's labor, the promotion of "human flourishing," or the fostering of "a just and attractive culture," William W. Fisher III, Property and Contract on the Internet, 73 Chi.-Kent L. Rev. 1203, 1212-15 (1998).
• n14. See Ronald Dworkin, Hard Cases, 88 Harv. L. Rev. 1057, 1059 (1975) (distinguishing between "arguments of policy," which justify action by reference to a collective goal, and "arguments of principle," which justify action by reference to an individual or group right).
• n15. U.S. Const. art. I, 8, cl. 8.
• n16. Graham v. John Deere Co., 383 U.S. 1, 9 (1966); see also Merges et al., supra note 13, at 135 (stating that the "central theory behind patent law" relies on its value in providing "a market-driven incentive to invest in innovation").
• n17. See Merges et al., supra note 13, at 15 (observing that the usual justification for patent protection requires that the protection be tuned to achieve a proper balance between the benefits of encouraging invention and the costs of temporarily restricting the invention's use).
• n18. See In re Bergstrom, 427 F.2d 1394, 1401 (C.C.P.A. 1970) (reversing the patent examiner's rejection of claims for purified prostaglandins); Parke-Davis & Co. v. H. K. Mulford Co., 189 F. 95, 103 (S.D.N.Y. 1911) (Hand, J.), aff'd, 196 F. 496 (2d Cir. 1912) (upholding a patent for purified adrenaline); 1 Donald S. Chisum, Chisum on Patents 1.02[9] (1991) (chronicling the development of an allowance for patents of purified natural products, beginning with the upholding of a patent on aspirin in 1910).
• n19. See In re Bergy, 563 F.2d 1031, 1036 (C.C.P.A. 1977) (declaring a biologically pure strain of bacteria to be patentable subject matter), cert. granted & vacated sub nom. Diamond v. Bergy, 444 U.S. 924 (1979) (mem.), vacated in part sub nom. Parker v. Bergy, 438 U.S. 902 (1978) (mem.), on remand sub nom. In re Bergy, 596 F.2d 952 (C.C.P.A. 1979), cert. granted sub nom. Diamond v. Chakrabarty, 444 U.S. 1028 (1980) (mem.), aff'd, 447 U.S. 303 (1980).
• n20. The pace of patenting has been so fierce that one industry analyst has remarked that current applications may seek to patent the human genome eight times over. See Tom Abate, Worms and Germs Bait Biotech's Hooks, S.F. Chron., Jan. 12, 2000, at D1.
• n21. The PTO has itself been puzzled. Most of the thousands of applications for patents on gene fragments "have been stalled because of enduring questions over exactly what can be patented." Martin Enserink, Patent Office May Raise the Bar on Gene Claims, 287 Science 1196, 1196 (2000). In response to complaints that its standards for patenting gene fragments were too lax, the PTO has published new guidelines that reflect a determination to require more substantial showings of patent utility. See Utility Examination Guidelines, 66 Fed. Reg. 1092, 1098 (2001) (requiring that examiners reject patent applications for inventions that lack "a well-established utility" and for which the applicant has disclosed no "specific and substantial utility"); see also Enserink, supra, at 1197 (quoting the PTO's director of biotechnology as predicting that many gene fragments "will have a difficult time" meeting the "clarified" utility requirement).
• n22. Concerned about restrictions on future research or about insults to science's own "economy of credit," Mario Biagioli, The Instability of Authorship: Credit and Responsibility in Contemporary Biomedicine, 12 Life Sci. Forum 3, 3-5 (1998) (describing a scientific "economy of credit," in which individuals must put discoveries in the public domain if they wish to accumulate rewards of status and reputation), scientists and representatives of scientific organizations have repeatedly spoken out against the awarding of monopolies on genetic materials, particularly the patenting of genetic sequences of unknown biological function. See, e.g., Declan Butler & Paul Smaglik, Celera Genome Licensing Terms Spark Concerns Over "Monopoly', 403 Nature 231, 231 (2000); Enserink, supra note 21, at 1196 (citing the concern of an official at the National Institutes of Health that gene patents could act as "a big disincentive for biomedical research"); Eliot Marshall, Patent on HIV Receptor Provokes an Outcry, 287 Science 1375, 1377 (2000) (reporting the frustration of Dr. Robert Gallo, director of the University of Maryland's Institute of Human Virology, with the unfairness of awarding a gene patent to a company that had filed a patent application before academic researchers did the hard work of determining its connection to HIV). Others have expressed ethical and religious concerns about the patenting of genes. See Ronald Cole-Turner, Religion and Gene Patenting, 270 Science 52, 52 (1995).
• n23. For examples of commentators who have criticized expansion of the reach of patent protection, see Roberto Mazzoleni & Richard R. Nelson, The Benefits and Costs of Strong Patent Protection: A Contribution to the Current Debate, 27 Res. Pol'y 273, 279, 281 (1998) (expressing amazement at the rush to patent gene fragments and arguing that "a general broadening and strengthening of patent rights" lacks economic justification), and Michael S. Greenfield, Note, Recombinant DNA Technology: A Science Struggling with the Patent Law, 44 Stan. L. Rev. 1051, 1091-92 (1992) (suggesting that awarding patents for gene fragments could distort current market incentives for research and inhibit future technological advance). Such academic expressions of anxiety have had company in the popular press. See, e.g., Richard Saltus, Priceless Letters, Boston Globe, Mar. 28, 2000, at D1 ("Many people suddenly seem baffled and outraged at how the essence of humanity - the DNA blueprint - has become the genetic equivalent of the Yukon Territory, with private biotech prospectors staking patent claims right and left."); Robert Krulwich, Genetic Code Landlords: Is Business Getting in the Way of Good Scientific Research?, in The World News Tonight (ABC television broadcast, Feb. 28, 2000) <http://abcnews.com/onair/CloserLook/wnt<uscore>000228<uscore>CL<uscore> Genomics<uscore>feature.html> (raising concerns that gene patents could block, or at least slow, research into cures for disease). Lobbyists for medical research have gone so far as to call gene-patenting companies "the robber barons of the genetic age." Genetic Face-Off: Scientists, Corporation Feud Over Gene Patent, in The World News Tonight (ABC television broadcast, Feb. 28, 2000) <http://abcnews.go.com/sections/living/Daily News/genepatent000228. html>.
• n24. See Eliot Marshall, Clinton and Blair Back Rapid Release of Data, 287 Science 1903, 1903 (2000) (reporting an exhortation by the British and American heads of state that private companies make raw genetic data publicly available and use patents responsibly).
• n25. See Lewis M. Branscomb & James H. Keller, Towards a Research and Innovation Policy, in Investing in Innovation: Creating a Research and Innovation Policy That Works 462, 472, 476 (Lewis M. Branscomb & James H. Keller eds., 1998) (concluding that the biotechnology and pharmaceuticals industries demand strong patent protection); Walter, supra note 9, at 1048 ("Denying patents for bio-technology will result in the inhibition of competitively priced goods and a reduced initial incentive to engage in biotechnological studies.").
• n26. See, e.g., Saltus, supra note 23, at D1 (quoting the statement of an official of the Biotechnology Industrial Organization that "for patients awaiting therapies and cures for deadly disease, there is hardly a more important issue than patents"); S. M. Thomas et al., Ownership of the Human Genome, 380 Nature 387, 387 (1996) (observing that companies view patent monopolies "as essential to successful commercial exploitation"). As late as 1998, this view seemed that of the PTO's director of biotechnology examination, John Doll. See John J. Doll, The Patenting of DNA, 280 Science 689, 689-90 (1998) ("It is only with the patenting of DNA technology that some companies, particularly small ones, can raise sufficient venture capital to bring beneficial products to the marketplace or fund further research.").
• n27. The United States was the priority country for 63% of the sets of international patents filed in the first half of the 1990s, and for 59% of the most highly cited biotechnology inventions. See Lawrence M. Rausch, International Patenting Trends in Biotechnology: Genetic Engineering, Division of Sci. Resources Stud. Issue Brief (Nat'l Sci. Found., Arlington, Va.), NSF 99-351, June 18, 1999.
• n28. See Lewis & Watson, supra note 9, at B1.
• n29. President's Statement on Signing S. 1111, 31 Weekly Comp. Pres. Doc. 1966 (Nov. 1, 1995) (affirming the desirability of strong patent protection because "American companies working to commercialize breakthrough products should not be required to face unfair competition from overseas"). Critics of patent protection have characterized America's role as an international champion of strong patent protection as "heavily freighted with national interest." Mazzoleni & Nelson, supra note 23, at 273.
• n30. See Saltus, supra note 23, at D4.
• n31. See id. at D1 (listing eight drugs that produce over $ 100 million in revenue each year). According to the editor of the Medical Technology Stock Letter, "more than half of all new drugs approved today are coming out of the biotech sector." Daniel Kadlec, A Biotech Wreck, Time, Apr. 3, 2000, at 93.
• n32. See Kadlec, supra note 31, at 93; Ronald Rosenberg, Great Expectations: Surge in FDA Applications Seen Paying Dividends in 2001, Boston Globe, Jan. 10, 2001, at D4; Wall $ treet Roundup, Genetic Engineering News, Feb. 1, 2000, at 10. Although agricultural biotechnology is not a primary concern of this Article, it is worth pointing out that American citizens who have not benefited from modern biotechnology in a trip to the doctor have almost certainly encountered it in a trip to the grocery: more than 30% of American-grown crops such as corn and soybeans derives from genetically modified seeds. See Peter J. Howe, Biotech Leaders, Foes Come to Town: Events Reflect Two Sides on Genetic Engineering, Boston Globe, Mar. 26, 2000, at A1; see also Martin Teitel, A Bill of Rights for Everyone's Protection, Boston Globe, Mar. 26, 2000, at E7 (claiming that "60% of our processed food is genetically engineered"). Furthermore, many believe that biotechnology has only begun to tap into its potential to produce new methods of diagnosis and treatment. See A Survey of the Human Genome, supra note 6, at 5-8. Although still in its infancy and not without setbacks, see Cowley & Underwood, supra note 8, at 61, gene therapy - therapy through the manipulation and alteration of an individual's genes - has already helped some individual heart patients and offers the possibility of a new breed of "miracle" cures. See Stipp, supra note 8, at F-23.
• n33. 35 U.S.C. 161-164 (1994 & Supp. IV 1998).
• n34. 7 U.S.C. 2321-2582 (1994).
• n35. Roscoe Pound, Law in Books and Law in Action, 44 Am. L. Rev. 2, 15 (1910).
• n36. See, e.g., Kenneth J. Burchfiel, Biotechnology and the Federal Circuit 4.2, at 51-52 (1995) (asserting that patent law's requirement of "practical utility" "depends on continuing agreement with respect to the policy that best promotes the "useful arts,' and the balance of competition and compensation in the pharmaceutical or biotechnology fields"); D. Benjamin Borson, The Human Genome Projects: Patenting Human Genes and Biotechnology. Is the Human Genome Patentable?, 35 IDEA 461, 496 (1995) (hoping for patent legislation that will better "serve the [biotechnology] industry's needs"); Yusing Ko, Note, An Economic Analysis of Biotechnology Patent Protection, 102 Yale L.J. 777, 804 (1992) (recognizing that patent law's purpose is "the promotion of technological progress"); Walter, supra note 9, at 1025 (affirming that "patents stimulate the growth of industry, and the industry of biotechnology welcomes any patent protection that it receives"). The Court of Appeals for the Federal Circuit has acknowledged the significance of practical concerns in its rulings on patent validity. See In re Brana, 51 F.3d 1560, 1568 (Fed. Cir. 1995) (observing that requiring human clinical trials to show a drug's "utility" would eliminate financial incentives to develop many "potential cures"). One commentator has gone so far as to say that "many of the core issues affecting biotechnology patents essentially involve declarations of economic policy by the Federal Circuit." Burchfiel, supra, 18.5, at 473.
• n37. See, e.g., Rebecca S. Eisenberg, Patents and the Progress of Science: Exclusive Rights and Experimental Use, 56 U. Chi. L. Rev. 1017, 1017-18 (1989) (observing that "the idea that exclusive rights in new knowledge will promote scientific progress is counterintuitive to many observers of research science, who believe that science advances most rapidly when the community enjoys free access to new discoveries"); Rebecca S. Eisenberg, Proprietary Rights and the Norms of Science in Biotechnology Research, 97 Yale L.J. 177, 179 (1987) ("examining the interaction of intellectual property rights with research science norms in biotechnology-related fields" (internal citation omitted)); Eyal H. Barash, Comment, Experimental Uses, Patents, and Scientific Progress, 91 Nw. U. L. Rev. 667, 669 (1997) (noting that universities and nonprofit research institutions rely on "the free dissemination of knowledge").
• n38. Lewis M. Branscomb & Richard Florida, Challenges to Technology Policy in a Changing World Economy, in Investing in Innovation, supra note 25, at 3, 21 (calling for systematic consideration of United States policy toward innovation). David Mowery defines a "national innovation system" broadly to include both "the policy instruments and institutions conventionally associated with science and technology policy" and "regulatory policy, higher education, competition, and trade policies." David C. Mowery, The Changing Structure of the US National Innovation System: Implications for International Conflict and Cooperation in R & D Policy, 27 Res. Pol'y 639, 640 n.1 (1998).
• n39. This Article uses "the university" to refer generally to universities, colleges, and research institutes, a grouping that does not seem unreasonable, given that research institutes typically replicate graduate school research environments and are often associated with a hospital or university. See Max Charlesworth et al., Life Among the Scientists: An Anthropological Study of the Australian Scientific Community 52, 57 (1989).
• n40. Henry Etzkowitz, The Norms of Entrepreneurial Science: Cognitive Effects of the New University-Industry Linkages, 27 Res. Pol'y 823, 823-24 (1998).
• n41. It was not initially clear that a patent system developed for an era of mechanical invention, see Pierre-Benoit Joly & Marie-Angele de Looze, An Analysis of Innovation Strategies and Industrial Differentiation Through Patent Applications: The Case of Plant Biotechnology, 25 Res. Pol'y 1027, 1028 (1996) (describing the patent system as "originally designed to protect mechanical inventions"), would prove so accommodating. See infra Part I.C.
• n42. This narrow definition of biotechnology, essentially coterminous with what some call more precisely molecular biotechnology, see Bernard R. Glick & Jack J. Pasternak, Molecular Biotechnology: Principles and Applications of Recombinant DNA 7-9 (1994), is intended to be consistent with the definitions currently used by the National Science Board, see National Science Board, Science and Engineering Indicators-1996, at 6-5 (1996), and the National Science Foundation, see Rausch, supra note 27. It seeks to avoid the confusion and awkwardness often engendered by broader definitions, which can sometimes be construed to encompass techniques for the breeding and use of living organisms that are as old as civilization itself. See Burchfiel, supra note 36, ch. 2, at 17; Martin Kenney, Biotechnology: The University-Industrial Complex 1-2 (1986); see also Glick & Pasternak, supra, at 7 (observing that a Hungarian engineer coined the term biotechnology in 1917 to describe a procedure for pig farming that used sugar beets as feed).
• n43. See James D. Watson et al., Recombinant DNA 3-5 (2d ed. 1992) (describing the biologic functions of proteins). For quick introductions to biotechnological science, see In re O'Farrell, 853 F.2d 894, 895-99 (Fed. Cir. 1988); Borson, supra note 36, at 464-66; or Kathleen S. Matthews, Overview of Terminology and Advances in Biotechnology, in Biotechnology: Science, Engineering, and Ethical Challenges for the Twenty-First Century 3, 3-13 (Frederick B. Rudolph & Larry V. McIntire eds., 1996). For a more detailed and technical introduction to recombinant DNA technology and gene-sequencing techniques, see chapters two and three of Glick & Pasternak, supra note 42, at 17-82.
• n44. The full genetic sequence of an organism is called its genome. See Robert Cook-Deegan, The Gene Wars: Science, Politics, and the Human Genome 20 (1994). A strip of DNA that contains the code for a particular protein is called a gene. See Matthews, supra note 43, at 6.
• n45. See Matthews, supra note 43, at 5. There are four chemical "letters" in the genetic code's "alphabet." See id. at 4-5. Combinations of three such "letters" specify particular amino acids, molecules that are linked together in a chain-like sequence to form proteins. See id. at 5; see also Joel Davis, Mapping the Code 45-48 (1990) (describing the process of producing proteins). Proteins are typically 100 or more amino acids in length. See Biochemical Components of Organisms, in 14 Encyclopaedia Britannica 884, 885 (15th ed. 1992).
• n46. See Davis, supra note 45, at 60-66. For a quick review of the study of genetics from Mendel through the modern recombinant DNA revolution, see Eric S. Lander & Robert A. Weinberg, Genomics: Journey to the Center of Biology, 287 Science 1777, 1777-82 (2000).
• n47. See Burchfiel, supra note 36, 2.1, at 18-22 (describing recombinant DNA techniques and their characteristic products); see also Watson et al., supra note 43, at 453-581 (discussing practical applications of recombinant DNA technology).
• n48. See Burchfiel, supra note 36, 2.1, at 20.
• n49. See Cook-Deegan, supra note 44, at 64-71 (chronicling the automation of DNA and protein sequencing in the 1980s); see also Anita Varma & David Abraham, DNA Is Different: Legal Obviousness and the Balance Between Biotech Inventors and the Market, 9 Harv. J.L. & Tech. 53, 73 (1996) (criticizing the decision in In re Bell, 991 F.2d 781 (Fed. Cir. 1993), for failing to recognize that more modern genetic engineering procedures had routinized previously "nonobvious" results). Success in DNA sequencing has produced the predictable spin-off benefit of greatly facilitating the identification of new proteins: Nature reported in December of 1999 that, whereas ten years earlier a researcher "would have been happy to identify two or three proteins a year," new genome data and mass spectrometry techniques make it possible for a single researcher "to identify hundreds of proteins within a week." Alison Abbott, A Post-Genomic Challenge: Learning to Read Patterns of Protein Synthesis, 402 Nature 715, 715 (1999).
• n50. One might wonder how it is possible to sequence the DNA of a species, given the existence of genetic variations among individual members of a species. A first answer might be that genetic variations within a species are frequently not as significant as one might think: variations between individual humans are confined to a mere 0.1% of the entire human genome. See Francis Collins, Director of the National Human Genome Research Institute, Speech at the Harvard Center for Genomics Research Seminar (Mar. 22, 2000). (By way of comparison, the chimpanzee and human genomes are 98% identical. See Ann Gibbons, Building a Case for Sequencing the Chimp, 289 Science 1267, 1267 (2000).) A second answer is that when researchers "sequence a species," they look to sequence the genomes of multiple individuals in that species, thereby accounting for most of the major variations. See Collins, supra; Golden & Lemonick, supra note 6, at 23.
• n51. See Richard Saltus, In Scientific Coup, Fruit Fly Genes Are Deciphered in Full, Boston Globe, Mar. 24, 2000, at A1.
• n52. See Paul Smaglik, Protein Structure Groups Seek to Draft Common Ground Rules, 403 Nature 691, 691 (2000); see also Philip E. Ross, Gene Machine, Forbes, Feb. 21, 2000, at 98, 100 (stating that the latest breed of automated DNA sequencers "would do to DNA workers what the steam shovel did to John Henry").
• n53. See Human Genome Program, U.S. Dep't of Energy, Human Genome Project Information (visited Feb. 29, 2000) <http://www.ornl.gov/TechResources/ Human<uscore>Genome/home.html>.
• n54. The United States government and Britain's Wellcome Trust have been the chief financial sponsors of the project, the cost of which was reported, in the spring of 2000, as somewhere in the vicinity of $ 250 million. See Begley, supra note 9, at 52.
• n55. See Richard Saltus, Project Reaches Milestone in Race to Decode Genetic Map, Boston Globe, Mar. 30, 2000, at A16.
• n56. See Kathryn Brown, The Human Genome Business Today, Sci. Am., July 2000, at 50, 50-51; Golden & Lemonick, supra note 6, at 19-20.
• n57. Among the latest targets of public DNA sequencing are the mouse, see Elizabeth Pennisi, Mouse Sequencers Take Up the Shotgun, 287 Science 1179, 1179 (2000), and the puffer fish, see David Gyranoski & Paul Smaglik, Puffer Fish Joins Genome Stampede, 408 Nature 6, 6-7 (2000).
• n58. See Eliot Marshall, Public-Private Project to Deliver Mouse Genome in 6 Months, 290 Science 242, 242-43 (2000); Antonio Regalado, Mining the Genome, Tech. Rev., Sept./Oct. 1999, at 56, 58.
• n59. See Smaglik, supra note 52, at 691.
• n60. See J. Craig Venter, President of Celera Genomics, Speech at Harvard Center for Genomics Research Seminar (Mar. 8, 2000).
• n61. See G. Steven McMillan et al., An Analysis of the Critical Role of Public Science in Innovation: The Case of Biotechnology, 29 Res. Pol'y 1, 2 (2000). The Biotechnology Industry Organization, a trade group headquartered in Washington, D.C., estimates that the industry consists of about 1,200 companies earning $ 13 billion in sales each year. See Antonio Regalado, The Great Gene Grab, Tech. Rev., Sept./Oct. 2000, at 48, 50.
• n62. See McMillan et al., supra note 61, at 2. Currently, about 65% of biotechnology firms specializing in genetic or protein engineering are located in California, the Northeast, or the Mid-Atlantic states. See CorpTech Demographic Analysis Reports: Biotechnology - Genetic Engineering Systems Demographics (visited Mar. 11, 2000) <http://www.corptech.com/Demographics/DemogReport.cfm?report=pbio-ge>; Corp-Tech Demographic Analysis Reports: Biotechnology - Proteins/Protein Engineering Systems Demographics (visited Mar. 11, 2000) <http://www.corptech.com/Demographics/DemogReport.cfm?report=pbio-pe>.
• n63. See Lynne G. Zucker & Michael R. Darby, Costly Information: Firm Transformation, Exit, or Persistent Failure, 39 Am. Behav. Scientist 959, 960, 963-64 (1996) (describing the value of "star" scientists and observing that the productivity of biotechnology firms bore a strong positive correlation to the intensity of ties with such "stars"). According to Zucker and Darby, in the early 1990s, one third of America's 207 "star" bioscientists?"bioscientists with more than 40 genetic sequence discoveries or 20 articles reporting such discoveries by 1990 in GenBank"?had affiliations or joint research projects with private firms. Id. at 963-64.
• n64. See, e.g., Eric J. Bolland & Charles W. Hofer, Future Firms: How America's High Technology Companies Work 46 (1998) ("Almost invariably, the firms are started by people with PhDs in genetics or related sciences."); Kenney, supra note 42, at 94 ("All of the earliest genetic engineering companies were founded by professors.").
• n65. Biotechnology firms' close ties to the university are a somewhat intensified version of the relations between universities and "life science" companies as a whole. A 1996 survey indicated that more than 90% of United States life-science companies had ties with universities: 88% hired faculty as consultants, 59% funded university research, and 38% helped fund university training and education. See David Blumenthal et al., Relationships Between Academic Institutions and Industry in the Life Sciences - An Industry Survey, 334 New Eng. J. Med. 368, 369 (1996).
• n66. See McMillan et al., supra note 61, at 5. The figure increases to 83.5% if one includes papers produced by efforts that enjoyed both private and public funding. See id.
• n67. This measure does not strongly distinguish biotechnology from other high technology fields, however. See id.
• n68. In 1990, university patents constituted 18% of United States patents in genetic engineering and recombinant DNA technologies; 16% of United States patents in natural resins, peptides, and proteins; 12% of those in chemicals produced through techniques of microbiology or molecular biology; and 11% of those in organic compounds in patent class #536. See National Science Board, supra note 42, at 8-7. Notably, the three Cohen-Boyer patents for recombinant DNA technology, granted in 1980, 1984, and 1988 after prosecution by Stanford University, are commonly described as part of the foundation for the biotechnology industry. See F.M. Scherer, New Perspectives on Economic Growth and Technological Innovation 55-56 (1999); see also Merges & Nelson, supra note 4, at 905-06 (describing the unpatented Kohler-Milstein techniques for mass-producing monoclonal antibodies and the patented Cohen-Boyer techniques for gene splicing as the bases for the biotechnology industry).
• n69. Merges & Nelson, supra note 4, at 904.
• n70. In 1994, approximately 70% of United States biotechnology companies were less than 15 years old. See National Science Board, supra note 42, at 6-28.
• n71. Analysts estimate that there are about 1000 biotechnology companies that have less than 100 employees. See CorpTech Employment Trend Reports: Biotechnology Industry Report (visited Nov. 16, 2000) <http://www.corptech.com/EmpTrends/empreport.cfm?report=ibio>.
• n72. See Committee on Technology, Management and Capital in Small High-Tech Companies, National Academy of Engineering, Risk & Innovation: The Role and Importance of Small High-Tech Companies in the U.S. Economy 16 (1995) (visited Mar. 19, 2001) <http://books.nap.edu/ books/0309053765/html/R1.html>. Recent figures for the two subdivisions of biotechnology that most clearly relate to the subject matter of this Article - genetic and protein engineering - confirm the general impression that most such companies are no more than 20 years old (roughly 70% to 75%), have less than 100 employees (roughly 70% to 75%), and are private (roughly 55% to 65%). See CorpTech Demographic Analysis Reports: Biotechnology?Genetic Engineering, supra note 62; CorpTech Demographic Analysis Reports: Bio-technology?Proteins/Protein Engineering Systems, supra note 62.
• n73. Amgen Inc., the leading example, listed in a recent Form 10-K four commercial drugs that it manufactures and markets: sales of its two leading drugs generated more than $ 3 billion in revenue in 1999 alone. See Amgen Inc., Form 10-K, Note 10 to the Consolidated Financial Statements (Mar. 7, 2000) <http://www.sec.gov/Archives/edgar/data/318154/0000898430-00-000676.tx>.</NT 2>
• n74. See Liz Kowalczyk & Ronald Rosenberg, Insurers Ask Proof of New Drugs' Efficacy, Boston Globe, Mar. 29, 2000, at A24; see also Competing in the New Millennium: Challenges Facing Small Biotechnology Firms: Hearing Before the Subcomm. on Tech. of the House Comm. on Science, 106th Cong. 12 (1999) (statement of Dr. John W. Holaday, Chairman and CEO of EntreMed, Inc., a biotechnology firm based in Rockville, Md.) ("Holaday Statement") (asserting that "only one in 5,000 discoveries results in an approved drug twelve years later, at a cost in excess of $ 350 [million]"). In addition to the inherent difficulties of developing a safe and effective commercial drug, various regulatory hurdles help account for the long time needed to go from laboratory to market. See Wall $ treet Roundup, supra note 32, at 10 ("Biotech companies must overcome some of the highest hurdles facing any industry for getting products on the market."). Approval of a biotechnology patent frequently requires more than three years (more than the 18 months, on average, required to process patents in general), and a patentholder looking to market a drug must undergo a separate process, involving human clinical trials, before obtaining approval from the Food and Drug Administration. See Lisa Raines, Biotechnology and Patent Term Extension Issues, 54 Food & Drug L.J. 237, 237-38 (1999).
• n75. See Holaday Statement, supra note 74, at 13.
• n76. See Bolland & Hofer, supra note 64, at 44-47; see also Michael B. Davis, The Patenting of Products of Nature, 21 Rutgers Computer & Tech. L.J. 293, 335-36 (1995) ("Patents are frequently the primary property interest available to biotechnology companies for persuading possible investors, who generally do not understand the underlying technology, to take the necessary risks." (internal citations omitted)).
• n77. See D. Jane Bower & Erica Whittaker, Client Communication and Innovative Efficiency in US and UK Biotechnology Companies, in New Technology-Based Firms in the 1990s, at 36, 40 (Ray Oakey ed., 1994); cf. Peter S. Cohan, The Technology Leaders: How America's Most Profitable High-Tech Companies Innovate Their Way to Success 73-75 (1997) (describing Amgen Inc.'s strategic use of more than 37 "alliances" from 1984 to 1997).
• n78. In this context, "research partner" indicates that the two entities in question had entered some arrangement either jointly to conduct or to share the results of their research. See Bower & Whittaker, supra note 77, at 36.
• n79. See id. at 41.
• n80. See Branscomb & Florida, supra note 38, at 16-18.
• n81. See Donald E. Stokes, Pasteur's Quadrant: Basic Science and Technological Innovation 9-11 (1997).
• n82. See Branscomb & Florida, supra note 38, at 16 (recounting the new sense that technology responded as much to demands for products and better processes, as to advances in basic research).
• n83. See Stokes, supra note 81, at 12-23. The "cooperative model" of research and development might be understood as the triumph of the vision of science as "an organic whole, with complex interrelationships throughout," rather than as "the sum of two discrete parts, one pure and the other applied." Id. at 102 (internal quotation marks omitted) (quoting Report of the Panel on the McKay Bequest to the President and Fellows of Harvard College 7 (1950)).
• n84. See Branscomb & Florida, supra note 38, at 15.
• n85. See id. at 28 (noting the protectionist and nationalist concerns of "strong voices within both of the dominant political parties").
• n86. See id. at 17-18.
• n87. Stevenson-Wydler Technology Innovation Act of 1980, Pub. L. No. 96-480, 94 Stat. 2311 (1980) (codified as amended at 15 U.S.C. 3701-3714 (1994 & Supp. III 1998)) (requiring federal laboratories to facilitate technology transfer to private industry).
• n88. Patent and Trademark Amendments Act, Pub. L. No. 96-517, 94 Stat. 3015 (1980) (codified as amended in scattered sections of 35 U.S.C.).
• n89. See Branscomb & Florida, supra note 38, at 17-18.
• n90. See 15 U.S.C. 3710.
• n91. See David C. Mowery et al., The Effects of the Bayh-Dole Act on U.S. University Research and Technology Transfer, in Industrializing Knowledge: University-Industry Linkages in Japan and the United States 269, 274 (Lewis M. Branscomb et al. eds., 1999). Although Mowery and his co-authors suggest that the economic theory behind the Bayh-Dole Act is "based on little evidence," David Silverstein's historical account suggests that it might at least be supported by historical precedent. David Silverstein, Patents, Science and Innovation: Historical Linkages and Implications for Global Technological Competitive-ness, 17 Rutgers Computer & Tech. L.J. 261, 280-92 (1991) (describing the patent system's pre-industrial role "as an important link between the users and the early practitioners of science").
• n92. The hope that patent law could produce (politically and financially) cheap technological progress was apparently not new in our nation's history. Edward Walterscheid has concluded that the Constitutional Convention adopted the Intellectual Property Clause because "from the perspective of delegates seeking to devise a form of governance for a fledgling and impecunious national government, granting limited-term exclusive rights in the works of authors and inventors seemed the perfect solution to encouraging the progress of science and useful arts with the least expense." Edward Walterscheid, To Promote the Progress of Science and Useful Arts: The Background and Origin of the Intellectual Property Clause of the United States Constitution, 2 J. Intell. Prop. L. 1, 34-35 (1994).
• n93. Pub. L. No. 98-620, 98 Stat. 3335 (codified at 15 U.S.C. 1051 note (1994)).
• n94. Pub. L. No. 99-502, 100 Stat. 1785 (1986) (codified as amended at 15 U.S.C. 3701-3714 (Supp. III 1998)).
• n95. See David H. Guston, Technology Transfer and the Use of CRADAs at the National Institutes of Health, in Investing in Innovation, supra note 25, at 221, 224.
• n96. National Cooperative Research Act of 1984, Pub. L. No. 98-462, 98 Stat. 1815 (1984) (codified as amended at 15 U.S.C. 4301-4305 (1994)).
• n97. Small Business Innovation Development Act of 1982, Pub. L. No. 97-219, 96 Stat. 217 (1982) (codified at 15 U.S.C. 631 (1994)). Henry Etzkowitz interprets the United States' adoption of direct-funding programs such as the Small Business Innovation Research program as especially symbolic of "a substantive if not ideological commitment to a greater role for government in innovation." Henry Etzkowitz, Bridging the Gap: The Evolution of Industry-University Links in the United States, in Industrializing Knowledge: University-Industry Linkages in Japan and the United States, supra note 91, at 203, 229.
• n98. Omnibus Trade and Competitiveness Act of 1988, Pub. L. No. 100-418, 102 Stat. 1107 (1988) (codified as amended at 19 U.S.C. 2411-2420 (1994)).
• n99. Commentators have counted at least 14 congressional acts that strengthened intellectual property protection in the 1980s. See Mowery et al., supra note 91, at 302 n.5 (citing Michael L. Katz & Janusz A. Ordover, R&D Competition and Cooperation, Brookings Papers on Economic Activity: Micro-economics 137-92 (1990)). Fortification of the patent laws continued in the 1990s: among prominent enactments were the Biotechnological Process Patents Act of 1995, Pub. L. No. 104-41, 109 Stat. 351 (1995) (codified in scattered sections of 35 U.S.C.), which increased protections from foreign infringers, and the American Inventors Protection Act of 1999, a part of the Consolidated Appropriations Act of 2000, Pub. L. No. 106-113, 113 Stat. 1501, 1501A-552 to -554 (1999) (codified at 35 U.S.C.A. 297 (Supp. 2000)), which allowed for extensions of the 20-year-patent term to compensate for delays in processing patent applications.
• n100. See Mowery, supra note 38, at 643. The National Science Board acknowledges that since 1980 the federal role in science and technology has changed from one of funding "mission-oriented [research and development]" to "speeding the development, application, and commercialization of new technologies in areas likely to contribute to economic growth and other societal needs." National Science Board, supra note 42, at 4-18. According to the Board, in fiscal year 1994 the federal government was engaged in more than 70 federal cooperative technology programs, absorbing a total of about $ 2.7 billion in federal funds. See id. at 4-19.
• n101. See Mowery, supra note 38, at 646-48.
• n102. See Jackie Hutter, A Definite and Permanent Idea? Invention in the Pharmaceutical and Chemical Sciences and the Determination of Conception in Patent Law, 28 J. Marshall L. Rev. 687, 721-24 (1995) (describing the large pharmaceutical companies' increasing reliance on collaborations with small bio-technology companies and universities).
• n103. See Bower & Whittaker, supra note 77, at 40-41.
• n104. See Stokes, supra note 81, at 137-38; see also supra Part I.A.
• n105. See supra Part I.A.
• n106. Etzkowitz, supra note 40, at 823-24.
• n107. 35 U.S.C. 1-376 (1994). This Article focuses on 101 patents, rather than protections granted under the Plant Patent Act of 1930, 35 U.S.C. 161-164, or the Plant Variety Protection Act of 1970, 7 U.S.C. 2321-2582, each of which represents another statutory system potentially applicable to plant inventions. For a discussion of the Plant Patent Act by the Court of Appeals for the Federal Circuit, see Imazio Nursery, Inc. v. Dania Greenhouses, 69 F.3d 1560, 1562-68 (Fed. Cir. 1995). For a recent important decision involving the Plant Variety Protection Act, see Asgrow Seed Co. v. Winterboer, 513 U.S. 179 (1995) (holding that a farmer may sell seed for reproductive use only if that seed was originally saved for replanting the farmer's own land).
• n108. See 35 U.S.C. 102.
• n109. See id. 101.
• n110. See id. 103.
• n111. See id. 112 (requiring that claims be sufficiently precise, and their specification sufficiently informative, to allow a person skilled in the relevant art to use the invention).
• n112. See Robert L. Harmon, Patents and the Federal Circuit 2.1, at 39-40 (4th ed. 1998); Merges et al., supra note 13, at 131; see also In re Warmerdam, 33 F.3d 1354, 1358 (Fed. Cir. 1994). Harmon suggests that the sum of the three statutory categories may be more restrictive than the Supreme Court-endorsed super-category "anything under the sun that is made by man," Diamond v. Chakrabarty, 447 U.S. 303, 309 (1980) (internal quotation marks omitted) (quoting the legislative history of the Patent Act of 1952, S. Rep. No. 1979, at 5 (1952)). Harmon, supra, 2.1, at 40. Chisum disagrees, arguing that "the better and emerging view is that the three product classes exhaust all the kinds of structural entities made by mankind," 1 Chisum, supra note 18, 1.02, at 1-8; accord Harmon, supra, 2.2(a)(i), at 41 ("In general, those words have a meaning as broad as the human mind can range ... .").
• n113. 35 U.S.C. 101; see also Kewanee Oil v. Bicron Corp., 416 U.S. 470, 483 (1974) (requiring that a discovery fall "within one of the express categories of patentable subject matter").
• n114. See 1 Chisum, supra note 18, 1.02[7], at 1-32, 1-33. The classic statement of the "product of nature" doctrine came in Ex parte Latimer, 1889 Dec. Comm'r Pat. 123 (Comm'r Patents 1889), in which the patent commissioner asserted that the applicant could not obtain an exclusive right to a plant fiber that "nature had intended to be equally for the use of all men." Id. The Supreme Court appeared to embrace the doctrine in Funk Brothers Seed Co. v. Kalo Inoculant Co., 333 U.S. 127 (1948), in which the Court held invalid a patent for a mixed bacterial culture on the ground that the invention amounted to "no more than the discovery of some of the handiwork of nature" and was therefore "part of the storehouse of knowledge of all men." Id. at 130-31. The Supreme Court reaffirmed the doctrine in Chakrabarty, stating that "laws of nature, physical phenomena, and abstract ideas" are unpatentable, as are "a new mineral discovered in the earth or a new plant found in the wild." Chakrabarty, 447 U.S. at 309. The doctrine survives, see Ex parte Allen, 2 U.S.P.Q.2d (BNA) 1425, 1426 n.1 & 1427 (B.P.A.I. 1987) ("If the claimed subject matter occurs naturally, it is not patentable subject matter under Section 101."), but remains in tension with the sense that "the discovery of phenomena in nature, in applied form, is the rationale of the patent system," Harmon, supra note 112, 2.2(a)(ii), at 43. Judges and commentators have questioned whether the doctrine adds anything beyond what the doctrines of utility, novelty, and nonobviousness already require. See, e.g., Merck & Co. v. Olin Mathieson Chem. Corp., 253 F.2d 156, 162 (4th Cir. 1958) ("Where the requirements [for patentability] are met, patents upon products of nature are granted and their validity sustained."); 1 Chisum, supra note 18, 1.02[7], at 1-33. But see Harmon, supra note 112, 2.2(a)(ii), at 43 (suggesting that the "product of nature" doctrine may have independent force when novelty and nonobviousness are unclear).
• n115. See In re Mancy, 499 F.2d 1289, 1294 (C.C.P.A. 1974) (dictum) (stating that a strain of micro-organisms found in a soil sample was presumably unpatentable because "the strain, while new in the sense that it is not shown by any art of record, is, as we understand it, a "product of nature'"). But see In re Bergy, 563 F.2d 1031, 1036, 1038 (C.C.P.A. 1977) (declaring the Mancy dictum to have been "ill-considered," and finding a biologically pure strain of bacteria used in "an industrial process" to be a "manufacture" or "composition of matter"), cert. granted & vacated sub nom. Parker v. Bergy, 438 U.S. 902 (1978) (mem.), on remand sub nom. In re Bergy, 596 F.2d (C.C.P.A. 1979), cert. granted sub nom. Diamond v. Bergy, 444 U.S. 924 (1979) (mem.), vacated in part sub nom. Diamond v. Chakrabarty, 444 U.S. 1028 (1980) (mem.), aff'd, 447 U.S. 303 (1980).
• n116. See Chakrabarty, 447 U.S. at 320 (Brennan, J., dissenting) (asserting that the 1930 Plant Patent and 1970 Plant Variety Protection Act demonstrated Congress's understanding that 101 excludes living things); 1 Chisum, supra note 18, 1.02[7], at 1-50.1 to 1-50.2.
• n117. Just as this Article focuses on 101 patents to the exclusion of alternative protections for plant inventions, see supra note 107, it focuses in this Section on the law regarding 101 utility patents for biotechnology products, rather than the generally less controversial, and now to a large extent statutorily explicit, see supra note 99, standards for patenting biotechnology processes. Given that the Biotechnological Process Patents Act of 1995, Pub. L. No. 104-41, 109 Stat. 351 (1995) (codified in scattered sections of 35 U.S.C.), amended 35 U.S.C. 103 to allow the patenting of otherwise obvious biotechnological processes that operate on or produce a novel and nonobvious composition of matter, see 35 U.S.C. 103(b) (Supp. II 1996), the most fundamental residual problems in determining the patentability of biotechnology process patents largely overlap with the questions concerning the patentability of the processes' inputs or outputs.
• n118. 447 U.S. at 308-09 (holding that a genetically engineered bacterium was "a product of human ingenuity" that "plainly qualified as patentable subject matter").
• n119. Id. at 308 (internal quotation marks omitted) (quoting United States v. Dubilier Condenser Corp., 289 U.S. 178, 199 (1933)). Contrast the Court's rule of construction with that of Justice Brennan's dissent, which recalled "this Nation's deep-seated antipathy to monopolies" as reason to "be careful to extend patent protection no further than Congress has provided." Id. at 319 (Brennan, J., dissenting).
• n120. Id. at 309 (majority opinion).
• n121. See Schering Corp. v. Gilbert, 153 F.2d 428, 432 (2d Cir. 1946).
• n122. See In re Irani, 427 F.2d 806, 809 (C.C.P.A. 1970) (reversing the Patent Office's rejection of a patent for a crystalline form of a substance, as distinct from its non-crystalline form); In re Cofer, 354 F.2d 664, 667, 668 (C.C.P.A. 1966) (reversing the Patent Office's rejection of a patent for "free-flowing crystals," as distinct from a viscous liquid).
• n123. Parke-Davis & Co. v. H.K. Mulford & Co., 189 F. 95, 103 (S.D.N.Y. 1911) (L. Hand, J.), aff'd, 196 F. 496 (2d Cir. 1912) (upholding a patent for purified adrenaline); see also Kuehmsted v. Farbenfabriken of Elberfeld Co., 179 F. 701, 704-05 (7th Cir. 1910) (finding that re-crystallized aspirin was therapeutically different from the prior art).
• n124. In re Bergy, 596 F.2d 952, 972-73 (C.C.P.A. 1979) (internal quotation marks omitted) (quoting Bergy's response to the examiner's rejection of his claim), vacated in part as moot, Diamond v. Chakrabarty, 444 U.S. 1028 (1980) and aff'd in part, Diamond v. Chakrabarty, 447 U.S. 303 (1980).
• n125. The Federal Courts Improvement Act of 1982, Pub. L. No. 97-164, 96 Stat. 25 (1982), created the Court of Appeals for the Federal Circuit and gave it exclusive jurisdiction over all appeals of patent cases originally heard in the federal district courts. See Burchfiel, supra note 36, 1.2, at 5. In its first decision, the Federal Circuit held prior rulings of the Court of Claims and of the Court of Customs and Patent Appeals to be binding precedent. See South Corp. v. United States, 690 F.2d 1368, 1370 (Fed. Cir. 1982) (en banc).
• n126. See Joly & de Looze, supra note 41, at 1030 (reporting that international patents for distinguishable families of biotechnology inventions increased from about 500 per year in 1980 to about 2500 per year at the start of the 1990s).
• n127. See, e.g., Eisenberg, Patents, supra note 37, at 1018 (remarking a trend to increased availability of patents for biotechnology); Robert Harris, The Emerging Primacy of "Secondary Con-siderations" as Validity Ammunition: Has the Federal Circuit Gone Too Far?, 71 J. Pat. & Trademark Off. Soc'y 185, 201 (1989) (questioning the weakening of the test for nonobviousness); Varma & Abraham, supra note 49, at 56 (asserting that the Federal Circuit has tilted the nonobviousness standard too much in favor of biotechnology patent applicants). Significant decisions included the Federal Circuit's holding in Cross v. Iizuka, 753 F.2d 1040, 1050 (Fed. Cir. 1985), that a showing of in vivo utility was not necessary to patent an invention claiming a specific pharmacological effect, and the Federal Circuit's rejection, in In re Sigco Research, 36 U.S.P.Q.2d (BNA) 1380, 1382 (Fed. Cir. 1995), and In re Dow Chemicals Co., 837 F.2d 409, 472-73 (Fed. Cir. 1988), of the suggestion that an invention was obvious if prior art had rendered it "obvious to try."
• n128. See Mazzoleni & Nelson, supra note 23, at 274; Silverstein, supra note 91, at 310-12.
• n129. From 1982 through 1987, the Federal Circuit upheld 89% of district court findings of patent validity, a massive increase from the 30% rate of affirmation prior to the Circuit's creation. See Mazzoleni & Nelson, supra note 23, at 274 (citing D.R. Dunner, Special Committee on the Court of Appeals of the Federal Circuit, in American Bar Association, Section of Patent, Trademark, and Copyright Law, Annual Report 314-25 (1988)). In 1991, David Silverstein observed that "statistics as well as perceptions of the patent bar" showed the Federal Circuit to be "pro-patent," "the only significant exceptions to [Federal Circuit] decisions favoring patent owners having been with respect to issues that affect the reliability of and public confidence in the patent system." Silverstein, supra note 91, at 310-11.
• n130. In re Bergy, 596 F.2d 952, 985 (C.C.P.A. 1979) (internal quotations omitted), vacated in part as moot, Diamond v. Chakrabarty, 444 U.S. 1028 (1980), and aff'd in part, Diamond v. Chakrabarty, 447 U.S. 303 (1980).
• n131. At least one commentator feels, however, that the courts and, particularly, the PTO have still been insufficiently accommodating, giving unfavorable treatment to biotechnology patents in general and patents of multicellular animals in particular, at least when compared to patents of other kinds of inventions. Burchfiel, supra note 36, 6.11(d), at 143 ("The biotechnology industry has a right to an explanation of why it is easier to patent a mousetrap in [the PTO's] Group 320 than a mouse in Group 180, and to demand from the courts and Congress that disparate and unique standards of patentability no longer be applied to biotechnology inventions."). Undeniably, the PTO has historically taken significantly longer than average to process biotechnology patent applications. See Raines, supra note 74, at 237-38 (observing that it can take more than three years to obtain approval or denial of a biotechnology patent); Joly & de Looze, supra note 41, at 1029-30 (reporting that in July 1988, 5850 biotechnology patent applications still awaited action by the PTO and that, on average, examination of biotechnology patents did not begin until 15.5 months after the filing date). However, PTO delays may principally reflect the novelty of biotechnology's subject matter, rather than truly disparate treatment by the PTO. See Raines, supra note 74, at 237. In any case, Congress has now provided for relief in the event of a PTO-induced delay. The American Inventors Protection Act of 1999, part of the Consolidated Appropriations Act of 2000, Pub. L. No. 106-113, 113 Stat. 1501, 1501A-552 to -554 (1999) (codified at 35 U.S.C.A. 297 (2000)), allows an extension of a patent's 20-year term to compensate for a processing delay caused by PTO (in)action or by appeals or interference proceedings. See US Okays Patent Reform Bill, 17 Nature Biotech. 939, 939 (1999).
• n132. 927 F.2d 1200, 1218 (Fed. Cir. 1991) (upholding a patent for a DNA sequence coding for a known therapeutic agent).
• n133. Watson et al., supra note 43, at 1.
• n134. See Amgen, 927 F.2d at 1206 ("A gene is a chemical compound, albeit a complex one ... ."); see also Burchfiel, supra note 36, 2.2(a), at 23-24 ("Product claims may be directed to the DNA sequence of a gene or a portion of a gene, to novel protein products, to known proteins having a specified degree of purity or minimum activity, or to various products containing the DNA sequence.").
• n135. See Pioneer Hi-Bred Int'l, Inc. v. J.E.M. AG Supply, Inc., 200 F.3d 1374, 1378 (Fed. Cir. 2000) (holding that modified seeds and seed-grown plants are patentable subject matter); Ex parte Hibberd, 227 U.S.P.Q. (BNA) 443, 444 (B.P.A.I. 1985); Burchfiel, supra note 36, 3.4, at 46.
• n136. See Ex parte Allen, 2 U.S.P.Q.2d (BNA) 1425, 1426-27 (B.P.A.I. 1987) (declaring that oysters made polyploid through the application of hydrostatic pressure were patentable subject matter); see also U.S. Patent No. 4,736,866 (Leder et al.) (issued Apr. 12, 1988) (patent for a genetically engineered mouse).
• n137. See Burchfiel, supra note 36, 2.5, at 32 (commenting that the PTO had effectively imposed a moratorium on higher-vertebrate patents); Walter, supra note 9, at 1036-37 (noting that "sensitivity to political pressures has affected the number of patents and the willingness of the PTO to actually grant animal patents," and that no court has yet decided whether the PTO exceeded its powers in granting patents for genetically modified multicellular animals). In 1999, the PTO rejected an application for a patent that described a human being. See Rick Weiss, US Ruling Aids Opponent of Patents for Life Forms, Wash. Post, June 17, 1999, at A2.
• n138. In Amgen, Inc. v. Chugai Pharmaceutical Co., 13 U.S.P.Q.2d (BNA) 1737 (D. Mass. 1989), aff'd in part, rev'd in part, vacated in part, 927 F.2d 1200 (Fed. Cir. 1991), the district court made the traditional symbolic obeisance to the doctrine, declaring that the DNA sequence at issue was only patentable because it was the ""purified and isolated' DNA sequence encoding EPO [erythropoietin]" and was "not ... the DNA sequence encoding human EPO," which was "a nonpatentable natural phenomenon." Id. at 1759.
• n139. See Burchfiel, supra note 36, 5.4, at 65; Harmon, supra note 112, 3.1, at 69.
• n140. See, e.g., Regents of the Univ. of Cal. v. Eli Lilly & Co., 119 F.3d 1559, 1574 (Fed. Cir. 1997) (holding that the district court did not commit clear error in finding a patent's written description inadequate); Fiers v. Revel, 984 F.2d 1164, 1170-71 (Fed. Cir. 1993) (holding that, if a DNA sequence is claimed, the specification must describe the DNA itself, not just "a potential method for isolating it"). But see In re Lundak, 773 F.2d 1216, 1224 (Fed. Cir. 1985) (reversing the PTO's rejection of a patent application for failure to meet the deposit requirement before the filing date). In 1999, Congress re-emphasized the importance of disclosure by providing for pre-approval publication, within 18 months of filing, of patent applications also filed abroad. See U.S. Dep't of Commerce, Commerce Secretary William M. Daley Applauds Passage of American Inventors Protection Act (press release of Nov. 22, 1999) <http://osecnt13.osec.doc.gov/public. nsf/docs/1B5218DEB6A5F440852568320051D4ED>.
• n141. See Amgen, Inc. v. Chugai Pharm. Co., 927 F.2d 1200, 1213-17 (Fed. Cir. 1991) (invalidating certain broad and vague claims as insufficiently enabled).
• n142. Raytheon Co. v. Roper Corp., 724 F.2d 951, 958 (Fed. Cir. 1983); see also Brooktree Corp. v. Advanced Micro Devices, Inc., 977 F.2d 1555, 1571 (Fed. Cir. 1992) (stating that challenger to a patent's utility needs to show that the challenged invention is "totally incapable of achieving a useful result"); Stiftung v. Renishaw PLC, 945 F.2d 1173, 1180 (Fed. Cir. 1991) (holding that there is no need for an invention to represent "the best or the only way to accomplish a certain result," or to be completely satisfactory in accomplishing that result); Harmon, supra note 112, 2.3(a), at 54 (noting that utility is generally loosely construed); Merges et al., supra note 13, at 129 ("Utility ... has devolved over the years into a rather minimal obstacle to obtaining a patent.").
• n143. See Sheldon W. Halpern et al., Fundamentals of United States Intellectual Property Law: Copyright, Patent, and Trademark 2.4, at 217-18 (1999).
• n144. 383 U.S. 519 (1966).
• n145. Id. at 531; see also Bindra v. Kelly, 206 U.S.P.Q. (BNA) 570, 575-76 (B.P.A.I. 1979) (finding, in an interference hearing (where the threshold for showing practical utility is heightened), that practical utility was not established for a compound claimed to be useful in preparing a prostaglandin, where the prostaglandin-producing reaction had not been carried out); In re Kirk, 376 F.2d 936, 942, 945-46 (C.C.P.A. 1967) (holding that a substance was not "useful" when its only known use was as an intermediate substance in the production of a compound that itself lacked a known utility); In re Joly, 376 F.2d 906, 908-09 (C.C.P.A. 1967) (same).
• n146. Brenner, 383 U.S. at 534-35.
• n147. See Enserink, supra note 21, at 1196; Krulwich, supra note 23.
• n148. See In re Ziegler, 992 F.2d 1197, 1203 (Fed. Cir. 1993).
• n149. Utility Examination Guidelines, 66 Fed. Reg. 1092, 1094 (2001); see also Enserink, supra note 21, at 1197 (quoting the PTO's director of biotechnology as saying that many DNA fragment applications "will have a difficult time" meeting the new utility requirement, which demands a "substantial, real-world utility," rather than "throwaway" utilities such as claimed potential uses in forensic science); see also Paul Smaglik, ... As US Tightens Up on "Speculative' Claims, 403 Nature 3, 3 (2000).
• n150. See Varma & Abraham, supra note 49, at 56 (arguing that, under the Federal Circuit's tutelage, the requirement for nonobviousness has weakened substantially).
• n151. See In re Vaeck, 947 F.2d 488, 494 (Fed. Cir. 1991) (affirming the dual requirement of motivation and enablement); Ex parte Tanksley, 37 U.S.P.Q.2d (BNA) 1382, 1386 (B.P.A.I. 1994) (same).
• n152. In re O'Farrell, 853 F.2d 894, 903-04 (Fed. Cir. 1988) (asserting that the predictability of success is the crucial factor in determining obviousness).
• n153. Ex parte Gray, 10 U.S.P.Q.2d (BNA) 1922, 1924-25 (B.P.A.I. 1988) (recognizing the existence of unexpected properties as sufficient to rebut prima facie obviousness); see also Burchfiel, supra note 36, 6.5, at 95 (citing as examples of unexpected properties "superior purity or specific activity ... , or unexpected yield").
• n154. See, e.g., Burchfield, supra note 36, 6.9, at 118 (observing that because of the general lack of understanding of the relation between protein function and structure, "even very close homology ... may provide no motivation").
• n155. See In re Bell, 991 F.2d 781, 784 (Fed. Cir. 1993) (upholding a patent that claimed only a few of 10[su'36'] possible nucleotide sequences for a known protein).
• n156. 35 U.S.C. 103 (1994).
• n157. Judging nonobviousness may not be as difficult with regard to semiconductor chip technology because, although that field is rapidly developing, disputes are more likely to surface soon after invention or discovery. See Eliot Marshall, Biotech Giants Butt Heads over Cancer Drug, 288 Science 2303, 2303 (2000). By way of contrast, because biotechnology products typically take years to develop, patent disputes may not take shape until the bounds of "obviousness" have changed substantially from their position at the time of invention. See id.
• n158. See Varma & Abraham, supra note 49, at 73 (arguing persuasively that the Federal Circuit was fooled by clever attorney arguments in In re Bell, 991 F.2d at 781?in particular, by citation of the large, but largely irrelevant, number (10[su'36']) of potential DNA sequences that could code for a given protein).
• n159. Graham v. John Deere Co., 383 U.S. 1, 6 (1966).
• n160. Henry Etzkowitz & Loet Leydesdorff, The Dynamics of Innovation: From National Systems and "Mode 2" to a Triple-Helix of University-Industry-Government Relations, 29 Res. Pol'y 109, 111 (2000).