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CASE STUDY: Patenting Human Genes

Authors: Nathan Romine, Mishel Stephenson, Julita Uthe, Huaxun Ye, and Liping Chen

04/22/2011; Gently Revised 2013

Background: This case study addresses the issue of ‘ownership’ of human genes. The Human Genome Project (HGP) aimed to determine the sequence of human genome. The project began in 1989 and was headed by DOE (Department of Energy) and NIH (National Institute of Health), but was first completed by Craig Ventner, whose lab developed new methods for gene mapping. The Human Genome Project quickly raised many ethical, legal, economic, and social issues. One important issue concerns the ownership of human genes. Because gene patents often have significant human and economic benefits, researchers now typically pursue patent protection for new discoveries and genetic inventions. Defenders urge that patents reflect appropriate recognition for the work of research, and that patents spur innovation and development that would otherwise not take place. Critics of gene patents argue that these patents inhibit access to research results, impede subsequent research, and constrain access to patented research results. The U.S. Patent and Trademark Office (USPTO) has issued thousands of patents on human genes that have been removed from human bodies and scientifically isolated and manipulated in a lab. Although they are occasionally challenged (as in the case under discussion here) these gene patents are now fairly settled features of U.S. patent law. However, to say that these patents are legal is not to say that they are good public policy or that they are morally justifiable. Some people argue that human gene patents are immoral even if they are entirely justifiable under existing U.S. law.

In US law, patents have their origins in the constitution (Article 1 section 8) and in the Patent act, 35 U.S.C. 101. The act states:

“Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.”

The legal question, then, is whether the claims in a patent fit under this description: that is, whether they are a new and useful process, a machine, a manufacture, a composition of matter, or a “new and useful improvement” of one of these things.

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The United States has been patenting chemical compositions based upon human extractions for over 100 years. The first patent for such a chemical was granted on March 20, 1906 for adrenaline and the second one is in 1923 for insulin. But raw natural material (organism) was not patented by USPTO until after a DNA product isolated and purified in1970s. Approximately 40,000 United States patents were related to 2,000 human genes (10% of human genome). The patent of human genes is being issued on isolated genes, methods of using the isolated genes, and methods to diagnose a disease based on an association between a gene and a disease. There is some controversy over whether these patents provide researchers an incentive to advance technology or hinder health access and medical research. There is also some controversy over whether and to what extent companies controlling gene patents hinder clinical research and practice. The price of medical treatments is also a controversy. One of the human genetic information patenting issues that has recently caused a profound public controversy was a Myriad patent on BRCA or breast cancer associated genes. After Collaborative international consortium has located the BRCA1 gene on human chromosome 17, scientist from the University of Utah who were part of the consortium created a company named Myriad. The company then commercialized the fully sequenced gene. Myriad patented the BRCA sequences isolated or outside of the human body (“sequence claims”) as well as the act of looking at individuals’ BRCA gene sequence and comparing it to known sequence (“correlation claims”). By strictly enforcing its patent rights, Myriad has been able to charge a premium price for BRCA testing. The focus of this study is a public controversy: Is it morally and ethically right to patent BRCA genes and their correlations with breast cancer? Are Myriad BRCA1 patents valid claims?

ACTIVITY: You will be assigned one of four interest groups, HUGO, Myriad Genetics, AMA, and CGS. As members of these groups, you will understand yourselves to have been called to give testimony concerning Myriad’s BRCA patents to a legislative committee. The HUGO and Myriad Genetics are groups in favor of human genes patenting while AMA and CGS are groups against human genes patenting. After reading the general background and the background for your group you will write your arguments in support of your group’s position. Be prepared to explain and defend your group’s view in class. No matter which group you are assigned into, you should articulate what you take to be the strongest arguments in favor of the position of your assigned group. All group members should participate in the presentation. As you prepare your presentation, you might find it useful to consider arguments likely to be made by opposing groups.

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Interest Groups: Group 1: Human genome Organization (HUGO) Human genome Organization (HUGO) was established in 1989 as an international organization, primarily to foster collaboration between genome scientists around the world. One of the many HUGO objectives is “ to sponsor factually-grounded dialogues on the social, legal, and ethical issues related to genetic and genomic information and championing the regionally-appropriate, ethical utilization of this information for the good of the individual and the society” HUGO believes that patenting DNA sequences may reward routine scientific discoveries. Patenting provides the necessary incentives for the ongoing development of products without interfering unduly with scientific research. However, it stands firm against patenting DNA sequences obtained by sequencing before the biological function has been discovered. HUGO also believes that licensing should be facilitated so more people are able to negotiate with patent holders and benefit from the use of patented sequences. In this way, both the patent holder can benefit from the licensing fees and a monopoly over the sequences can be avoided. As a representative of HUGO, you will argue that gene patents are appropriate and justifiable, and that the BRCA patent should be upheld. However, you should also recommend that such patents include a research exemption that permits researchers to use patented genetic materials without impedence. HUGO website: http://www.hugo-international.org/ Group 2: Myriad Genetics (BRCA)

Myriad Genetics is the corporation that owns the patents for the human genes BRCA1 and BRCA2 as well as the methods for identifying sequence mutations as indicators for a high likelihood of breast cancer. Myriad’s patents establish it as the sole source of the test to inform patients of their genetic risk of developing breast cancer.

As a representative for Myriad, you will defend the validity of the BRCA

patents, urging that such patents are a good way to promote research, and that isolated gene sequences are different from genes in their natural state and therefore are not excluded from eligibility for patent protection. Myriad Genetics website: http://www.myriad.com/

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GROUP 3: American Medical Association (AMA) Source: http://digitalcommons.wcl.american.edu/cgi/viewcontent.cgi?article=1003&context=pub_disc_briefs&sei-redir=1#search=%22amici+curae+medica+associations+against+BRCA%22 accessed March 30, 2011. Note: (Material below has been edited from the original, which can be found at

the link above.)

American Medical Association (AMA) is a private, voluntary non-profit organization of 240,000 physicians and medical students, who practice in all states and all fields of medical specialization. The AMA was founded in 1847 to promote the science and betterment of public health. From its inception, the AMA has maintained a Code of Medical Ethics, including a set of core Principles and a Code and Opinions applying those Principles.(…) In the mid-1990s, the American Medical Association amended its Code of Ethics to forbid doctors from patenting medical procedures because it found that these patents compromised patient care. Since that time, the AMA (with other medical and scientific groups) has issued numerous statements regarding the need to avoid having gene patents interfere with appropriate medical care and the development of better medical treatments and technologies, and declaring unethical any limitations on the dissemination of medical knowledge. (…) Patents are not needed to create an incentive for the discovery of human genes, and patent law does not exist to reward such scientific and medical discoveries. Rather, they must remain “free to all men and reserved exclusively to none,” both to meet shared ethical commitments and to foster further scientific discovery and more rapid sequential innovation. (…) AMA website: http://www.ama-assn.org/ Group 4: Center for Genetics and Society (CGS)

The Center for Genetics and Society (CGS) is a nonprofit information and public affairs organization working to encourage responsible uses and effective societal governance of the new human genetic and reproductive technologies. We work with a growing network of scientists, health professionals, civil society leaders, and others. The Center supports benign and beneficent medical applications of the new human genetic and reproductive technologies, and opposes those applications that objectify and commodify human life and threaten to divide human society.

The Center works in a context of support for the equitable provision of health

technologies domestically and internationally; for women's health and reproductive rights; for the protection of our children; for the rights of the disabled; and for precaution in the use of technologies that could alter the fundamental processes of the natural world.

CGS website: http://www.geneticsandsociety.org/

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READING GROUP 1: Human genome Organization (HUGO) Materials: “Statement on patenting of DNA sequences in particular response to the European Biotechnology Directive” HUGO intellectual property committee. April 2000. “Statement on the scope of gene patents research exemption, and licensing of patented gene sequences for diagnostics” HUGO intellectual property committee. December 2003. “The case for genomic patenting” by George Poste. Nature Vol 378. December 1995. URL: http://www.hugo-international.org/img/ip_gene_2003.pdf

Accessed: 19 April 2011

HUGO INTELLECTUAL PROPERTY COMMITTEE STATEMENT ON THE SCOPE OF GENE PATENTS RESEARCH EXEMPTION, AND LICENSING OF PATENTED GENE SEQUENCES FOR DIAGNOSTICS

December 2003

1 Introduction HUGO has taken the view that the granting of claims to DNA sequences in patents has the potential for a positive impact provided all the

requirements for patentability are met1. This position is consistent with

international treaties governing the field, especially the Agreement on Trade Related Aspects of Intellectual Property Rights (TRIPS) which ensures that product and process inventions in all areas of technology are eligible for patenting, and the European Directive 98/44/EC on the Legal Protection of Biotechnological Inventions. HUGO does not consider that there are any grounds to deviate from its previous statements. However, recent scientific and commercial developments in genomics have highlighted the possible conflicts which may arise between the need to provide incentives for the inventor and the need to protect the public interest. The purpose of this statement is:

- to provide additional comment on the standards for patentability of DNA molecules and their sequences in the light of new knowledge; - to draw attention to the need for a harmonised research exemption and - to suggest a possible mechanism for enabling cost effective licensing of patented DNA molecules and their sequences.

2 Standards for patentability As a result of the collaborative efforts of public institutions, databases comprising raw DNA sequences from human and other organisms are now publicly available. One effect of this development is

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that fewer patents are likely to be granted which claim such DNA sequences. In addition, growth in the annotation of raw sequence and the wide availability of sequence from model organisms is providing a sound basis for ”downstream‘ research, both broadening the basis for invention and potentially making increasingly difficult to meet the requirements for novelty and inventiveness in the isolation of DNA molecules and their sequences in general. In this regard HUGO has always emphasised the importance of the disclosure of function in respect of the criteria of patentability.

In many European countries, the acceptance of broad, product-based patents for DNA sequences is being questioned. This can partly be ascribed to the fact that a product patent traditionally covers all applications (uses) of the product, irrespective whether those uses were disclosed or claimed. HUGO notes that genes may be represented by many splice variants. Alternative splices in as many as 50% of our genes therefore complicate the definition of a gene. Moreover, biological functions in the human genome are not restricted to DNA sequences that encode proteins. From comparative genomics, it is increasingly clear that regulatory, structural and catalytic functions can be performed by DNA sequences that are transcribed but not translated (i.e. non-coding RNA) and genomic DNA directly (i.e. by sequences which are not transcribed).

HUGO takes the view that it should be generally understood that a claim on a DNA sequence does not extend to alternatively spliced transcripts if these have not been specified in the patent claim[s]. The issue raised by the question of alternative splicing is addressed by the guidance set out in HUGO‘s previous statement on the issue of the rights associated with claims to DNA sequences which overlap. In this statement, HUGO concurs with the Directive 98/44/EC (Recital 23) which states that determination of the DNA sequence as such without disclosure of its function does not constitute an invention, as well as with Recital 25, according to which, —when sequences overlap only in parts which are not essential to the invention, each sequences will be considered as an independent sequence in patent law terms.“ As HUGO pointed out in its statement of 2000, —the notion ”are not essential to the invention‘ is to be interpreted in the light of the function unambiguously disclosed by the respective applicant (patentee) and not on the basis of its objective (natural), not disclosed, importance as such.“ Regardless of how many forms of alternative splicing of a gene products exist, this guidance, developed to address the issue of overlapping sequences applies. Moreover, with reference to Article 9 of the Directive 98/44/EC, HUGO emphasizes that it should be interpreted along the same lines as Recital 25, i.e. the scope of a product patent on genetic information shall extend to all, but also only to material, in which the product (DNA molecules and their sequences) is incorporated and in which the genetic information is contained and performs its function. The performed function being that disclosed and claimed in the patent.

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In summary, HUGO has adopted the view that patents which claim DNA sequences should be available under certain conditions, namely disclosure of function. In the case of those DNA sequences which are identical with those found in nature, the invention of the product as such has to meet all the criteria of patentability. The scope of patents is determined by the courts. HUGO takes the view that it is not appropriate to advocate the introduction of a specific rule in respect of scope because to do so would limit the freedom of the courts.

3 Research Exemption HUGO considers that freedom to undertake research in genomics is fundamental to the acquisition of further knowledge and the development of applications to benefit human health. Researchers who wish to use patented technologies or products to further understanding in their work should not be unduly constrained by issues relating to licensing. In this respect, HUGO recognises the value of the exemption for research which is recognised in Europe. It is therefore of the opinion that a statutory research exemption should be introduced on a universal basis, irrespective of the final goal of research. HUGO recommends that the European statutory model of the exemption for research which covers all forms of research

for the

purpose of improving, or developing knowledge is used as a template.

4 Licensing of patented DNA molecules and their sequences for the development of diagnostics HUGO considers that the concept of the research exemption could be usefully extended to address the problems of access to patented gene sequences in the development of clinical diagnostics. The identification of DNA molecules and their sequences that are significantly implicated in a disease can provide the basis for a diagnostic test. For example, the BRCA1 gene which is implicated in some forms of breast cancer, has been used to develop such a test. The test is protected by product patents which assert rights over the DNA sequences (molecules) and the proteins they encode, and by use patents which contain claims to the use of the DNA sequences for diagnosis.

There has been considerable opposition to the grant of these patents, primarily because they confer on the owners of the patents not only an exclusive right on their own diagnostic method but also the ability to prevent others from competing with them through the development of improvements in the diagnostic methods, using the same sequences. Thus there are currently no other methods of diagnosing the presence of the breast cancer susceptibility gene BRCA1 that can be used without infringing the patents. The resulting exclusive ownership, and the fact that the owner of the patents has not licensed others to use its patents widely, have enabled the company to establish an exclusive market for the tests.

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To address the undue exclusivity that can be exercised in respect of diagnostics not only for patients with serious diseases but for a variety of other conditions, HUGO suggests the establishment of a clearing house to expedite the rapid and low cost licensing of patented DNA sequences which have potential applications in clinical diagnosis. This approach, initially suggested by the OECD, would provide mutual benefit for the owners of such patents and the research community. At present, the patent owner has to consider the onerous possibility of prosecuting infringers worldwide. The existence of a clearing house could not only obviate such outcomes but could lead to increased levels of licensing. At the same time, researchers, not the private sector, would have the option of securing licenses to patented sequences at a reasonable cost which might encourage the pursuit of research in areas which might have deterred them in the past. This approach would be of particular benefit to companies who are developing high throughput technologies for the rapid diagnosis of multiple gene variants who may need to acquire licences for large numbers of patented DNA sequences. HUGO encourages the OECD to pursue this idea, but could also itself play an active role as organizer of a Bermuda-Type conference on this issue.

HUGO Intellectual Property Committee 2003

° Professor Joseph Straus (Germany), Chair ° Professor Charles Auffray (France) ° Professor Jean-Jacques Cassiman (Belgium) ° Professor David R Cox (USA) ° Dr Peter N Goodfellow (UK) ° Dr Tim Harris (USA) ° Professor Ulf Landegren (Sweden) ° Professor Eric S Lander (USA) ° Dr Hatushi Shimizu (Japan) ° Dr Sandy Thomas (UK) ° Professor Gert-Jan B. van Ommen (NL) ° Mr Jacques Warcoin (France)

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HUGO INTELLECTUAL PROPERTY COMMITTEE STATEMENT ON PATENTING OF DNA SEQUENCES IN PARTICULAR RESPONSE TO THE EUROPEAN BIOTECHNOLOGY DIRECTIVE April 2000

http://www.hugo-international.org/img/ip_dna_2000.pdf Accessed: 19 April 2010

Since the very beginning of its activities HUGO has been closely watching patenting developments in the area of genomics and has analysed its possible impact specifically on further genome research. Notwithstanding its generally positive attitude toward patenting of useful benefits derived from genetic information, HUGO has repeatedly observed that Expressed Sequenced Tags (ESTs) constitute research tools and therefore opposed the patenting of short sequences from randomly isolated portions of genes and transcripts encoding proteins of uncertain functions. After the announcement of the US Patent and Trademark Office (US PTO) to grant patents on ESTs based on their utility as probes to identify specific DNA sequences, HUGO, in 1997, urged the US PTO and other offices with similar intention, "to rescind these decisions and, pending this, to strictly limit their claims to specified uses, since it would be untenable to make all subsequent innovation in which EST sequences would be involved in one way or other dependent on such patents."*

Since the publication of the 1997 Statement important developments have taken place: On July 6, 1998 the European Union adopted the Directive 98/44/EC of the European Parliament and of the Council on the legal protection of biotechnological inventions (OJ No. L 213/13 of 30.7.98) and on October 6, 1998 the US PTO issued to Incyte Pharmaceuticals, Inc., the US Patent No. 5,817,479 for "Human Kinase Homologs", the first patent so far known to include ESTs. Apart from this, the discovery of the importance of Single Nucleotide Polymorphisms (SNPs) for diagnostics and the attempts aimed at their patenting, led to the establishment of the non-profit SNP (TSC) Consortium of industry and academia. Co-sponsored by the Wellcome Trust and ten pharmaceutical companies, the Consortium expects to find some 300.000 SNPs in two years and put them into a publically accessible archive.

It is the view of the Intellectual Property Rights Committee of HUGO that these new developments do not change its previous positions, which in fact have been fully endorsed and confirmed by the most recent statements at the highest political level by the British Prime Minister Tony Blair and the US President Bill Clinton and also at the highest scientific level, by Bruce Alberts, President of the US National Academy of Sciences, and Sir Aaron Klug, President of the Royal Society of London.

However, HUGO's former statements require some comments and clarifications. In particular HUGO,

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--emphasizes its basic understanding that DNA molecules and their sequences, be they full-length, genomic or cDNA, ESTs, SNPs or even whole genomes of pathogenic organisms, if of unknown function or utility, as a matter of policy, in principle, should be viewed as part of pre-competitive information. Therefore efforts such as the new Consortium of industry and academia to map all SNPs and put them into public domain, are welcomed. Such Consortia will greatly contribute to innovation and stimulate international standardized use of data, which will beneficially influence, inter alia, cooperation between industry and academia;

--underscores and reiterates its previous call to patent offices not to issue patents on ESTs without having found balanced solutions for the obvious problem of arising dependencies;

-- expresses serious concerns about the negative impact on further progress of genomic research and successful exploitation of its results should broad claims of the so-called "having" and "comprising" type be issued for ESTs;

-- welcomes, in general, the adoption of the European Biotechnology Directive, in view of the necessary and beneficial clarifications it contains on such issues as patentable subject matter, specific patentability requirements, scope of protection and ethical aspects of patenting in the area of human genomics;

-- notes that the subject matter eligible for patent protection under the EU-Directive is consistent with HUGO's previous statements, in particular that a mere DNA molecule and its sequence without indication of a function does not contain any technical information and cannot constitute an invention; ñ stresses however the necessity that patent offices and courts, when examining the requirement of industrial application of the claimed DNA molecules and their sequences, to require an unambiguous indication and enabling disclosure of the function and to rigorously examine the indication of functions or the function disclosed;

-- welcomes, in principle, the attempt of the EU-Directive to provide for a statutory relief of the dependency issue by declaring sequences as independent in patent law terms, when they overlap "only in parts which are not essential to the invention," provided that:

i) the notion "are not essential to the invention" is to be interpreted in the light of the function unambiguously disclosed by the respective applicant (patentee) and not on the basis of its objective (natural), not disclosed, importance as such, and

ii) that claims of the broad "having" and "comprising" type, which cover not only the disclosed DNA sequence and its use but also products "having" or "comprising" that sequence, will be allowed only exceptionally when the information disclosed for the overlapping part is sufficiently enabling to the claimed invention;

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- maintains that SNPs, as a rule, cannot meet the requirement of inventiveness (non-obviousness);

- agrees, in principle, with the requirement of a free and informed consent of the donor, where a patent application is filed for an invention based on biological material of human origin or if it uses such material, but expresses concerns for the development of health care improvements in case national laws would require researchers and physicians to ask, over and above the required informed consent to the research planned, for specific consent for the filing of patent applications and the exploitation of research results based on such material;

- welcomes the clarification of the notion of ordre public or morality under which especially processes for cloning human beings, processes for modifying the germ line genetic identity of human beings and uses of human embryos for industrial or commercial purposes are declared unpatentable, under the reservation, however, that processes involving the culture and study of embryonic stem cells, genetically modified or not, and aimed at investigating a wide variety of diseases, aging, cancer and other health problems, are not affected by those exclusionary provisions;

- expresses concerns that reach-through patent claims and reach-through licenses, as partly accepted in the current practice, will not only seriously affect further research and development but could, eventually, discredit the entire patent system as an invaluable incentive to invent, innovate and invest in new technologies.

Members of HUGO's Intellectual Property Rights Committee:

Prof. David R. Cox Dr. Peter N. Goodfellow Dr. Tim J.R. Harris Prof. Eric Lander Dr. Kate H. Murashige Prof. Richard M. Myers Dr. Hatsushi Shimizu Prof. Joseph Straus (Chair) Maître Jacques Warcoin

In the preparation of this statement also the following HUGO Members participated:

Prof. Charles Auffray Prof. Jan-Jacques Cassiman Prof. Ulf Landegren Prof. Gert-Jan van Ommen (HUGO President 1998-99) Dr. Sandy Thomas

April 2000 © 1995 Nature Publishing Group

Reading on Following Pages: George Poste, The Case for Genomic Patenting. URL:http://www.nature.com.proxy.lib.iastate.edu:2048/nature/journal/v378/n6557/pdf/378534a0.pdf Accessed: 19 April 2011

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READING GROUP 2: Myriad Genetics (BRCA) The BRCA1 and BRCA2 gene patents include a range of different claims. This excerpt from a brief written by lawyers for Myriad Genetics focuses on the “composition claims” included in the patents in question. To make their case, Myriad must show (1) that the genes named in the patent are “patent eligible subject matter.” That is, the things covered in the patent are eligible for patent under US law. As partial support for this first claim, they argue (2) that the DNA named in the patent is a “composition of matter,” which falls under the language of US Patent law, and (3) that the DNA has been isolated and purified, so it is no longer in its natural state. Even though DNA would not be patentable in its natural state, Myriad points out that US law has supported other patents for otherwise natural compounds that have been isolated and purified. (4) In the development of patent law, judges have specified that “laws of nature, physical phenomena, and abstract ideas” are not eligible to be patented. So Myriad argues that the DNA claimed in the patent does not fall into any of these three categories. The lower court argued that the claimed DNA was a “Product of Nature,” and thus not eligible for patent, but Myriad argues (5) that products of nature are eligible for patent in some circumstances. In support of this fourth claim, they urge (6) that prohibiting patent for products of nature would be inconsistent with past practice, and (7) that such a prohibition would be “unworkable” since every composition of matter is, in some sense, a product of nature, and because the prohibition would rule out many other potentially lifesaving patent claims. As you read the brief, be sure to consider the supporting reasons provided for each of the seven main claims listed above. Materials downloaded 3/30/11 from http://www.aclu.org/files/assets/brca_appellantsbrief_20101022.pdf Paragraphs excerpted from Myriad Genetics’ appellants brief and edited for brevity (patent references removed, court case references abbreviated.) Myriad’s Research and Patents

Based on an innovative population-based study of cancer in a Utah Mormon community, the inventors of the patents-in-suit were able to unravel the genetic basis of BRCA1- and BRCA2-related cancer. By studying thousands of members of large families with clusters of cancer, the inventors amassed a large data collection, and then developed new techniques for mapping genetic polymorphisms to home in on the precise location of the BRCA1 gene within the human genome. The Myriad inventors were the first to isolate the BRCA1 DNA molecule, and they obtained patents covering their invention and associated methods for diagnosing a predisposition to breast and ovarian cancers. Myriad was then able to discover and isolate the BRCA2 molecule. The inventors obtained patents directed to this invention.

These isolated molecules are man-made chemical compositions, structurally and functionally distinct from any substance found in the human body—indeed, in all of nature. They are neither laws of nature, nor abstract ideas, nor mere

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information, but instead are useful as molecular tools (e.g., primers and probes) because of their ability to target and form stable chemical structures with a BRCA DNA sequence in a tissue sample. These isolated molecules can also be sequenced in the laboratory. These differences between the claimed isolated DNA molecules and genes found in the human body are critical to their distinct functions and real-world utilities. The claims do not cover genes in the human body. (emphasis added)

The District Court’s Ruling That DNA Patents Are Not Patent-Eligible

Plaintiffs and their amici urged the court to invalidate Myriad’s disputed patent claims under § 101, the Constitution, and for policy reasons, arguing that Myriad’s patents claims impede research, and block patient access to and increase costs for the BRCA diagnostic tests.

Myriad responded with evidence that its patents promote BRCA research, pointing out that over 18,000 researchers have conducted studies on BRCA, and over 7,000 relevant papers have been published, since the inventors disclosed these inventions to the public. Moreover, Myriad showed that patients now have ready access to the BRCA tests, 90% of which are covered by insurance (average co-pay: $100), and that Myriad provides patient assistance for those who cannot afford the test.

Plaintiffs and their amici also contended that the claimed isolated DNAs are non-patent-eligible products of nature, laws of nature, and natural phenomena. They further claimed that isolated DNAs are not “markedly different” from DNA inside the human body, yet they admitted that sequencing and detection could not be performed without those isolated molecules. Plaintiffs also urged that the claimed methods constituted mere information and thought, that the steps of the methods did not involve a transformation, that claims to “comparing” sequences cover “looking” at sequences and seeing if they are the same, and that any claims to the naturally occurring relationship between mutations and susceptibility to cancer are laws of nature and thus not patent-eligible. Myriad and its amici countered with showings that isolated BRCA DNA molecules are patent-eligible new and useful compositions of matter, that the isolated molecules do not exist in the body, and that they perform substantial utilities that cannot be performed by “native” genes in the human body.

If the Court reaches the merits, it should reverse. As to the composition-of-matter claims, each of which is drawn to isolated BRCA DNA molecules, those claims satisfy § 101. The isolated molecules fall within the literal language of that section, because they are undisputedly compositions of matter. They do not fall within any of the three narrowly cabined non-textual exceptions to § 101 (“laws of nature, physical phenomena, and abstract ideas”). To the contrary, these molecules are patent-eligible because such a holding is consistent with § 101’s command that “any” composition of matter that is “new and useful” is patent-eligible, and compelled by a long and consistent line of precedent and agency practice holding that molecules and substances isolated from naturally occurring products are “new” and thus patent-eligible compositions of matter. Moreover, they are not unpatentable because of any categorical restriction on patenting “products of nature.” Even were there a prohibition upon patenting “products of nature” that are

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not “markedly different” from the naturally occurring substances, Myriad was still entitled to summary judgment. Alternatively, the court erred by resolving fact questions against Myriad on summary judgment.

Because it is clear that Myriad’s patent claims cover patent-eligible subject matter as a matter of law, the judgment should be reversed, and summary judgment ordered in favor of Myriad. COMPOSITION CLAIMS ARE DRAWN TO PATENT-ELIGIBLE SUBJECT MATTER

If the Court reaches the merits, it should reverse and hold that Myriad’s challenged composition claims are patent-eligible under 35 U.S.C. § 101.

A. Isolated DNA Molecules Are “Compositions Of Matter” Under § 101 Section 101 of the Patent Act provides:

Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.

“In choosing such expansive terms . . . modified by the comprehensive ‘any,’ Congress plainly contemplated that the patent laws would be given wide scope.” Diamond v. Chakrabarty. This breadth “ensure[s] that ‘ingenuity should receive a liberal encouragement.’” Bilski v. Kappos.

The term “composition of matter” is to be understood “consistent with common usage.” In Shell Development, cited by the Supreme Court in Bilski and quoted with approval in Chakrabarty, the court held that the term “covers all compositions of two or more substances and includes all composite articles, whether they be results of chemical union, or of mechanical mixture, or whether they be gases, fluids, powders or solids.” Under this definition, the claimed isolated DNA molecules are unquestionably “compositions of matter,” or at the very least a “new and useful improvement” upon native DNA. As set forth at p. 6, above, DNA is a composition of “two or more substances”: nucleotides linked to each other by a phosphodiester backbone. See also In re Bergy (“the biologically pure culture of Bergy . . . clearly fit[s] into the plain terms ‘manufacture’ and ‘composition of matter’”). Indeed, plaintiffs’ district-court briefing repeatedly referred to Myriad’s “patented composition”, so there should be no dispute that isolated DNA molecules fall within the plain language of Section 101.

This is supported by the PTO’s 2001 Utility Examination Guidelines, issued after an extensive notice-and-comment process: Because Congress “specifically authorized issuing a patent to a person who ‘invents or discovers’ a new and useful composition of matter, . . . an inventor’s discovery of a gene can be the basis for a patent on the genetic composition isolated from its natural state and processed through purifying steps that separate the gene from other molecules naturally associated with it. . . . A purified DNA molecule isolated from its natural environment . . . is a chemical compound and is patentable if all the statutory requirements are met.” (emphasis in original).

Other provisions of the Patent Act—notably § 103(b), which presumes that patents are available for “nucleotide sequences”—confirm that Congress thought DNA molecules were patent-eligible. That subsection, added in 1995, requires that

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patents to “a biotechnological process” must also contain claims to the “composition of matter” that is “used in or made by” that process,” either in the same application or in another application with the same effective filing date. In § 103(b), Congress explicitly anticipated that “nucleotide sequences” would be one category of those patentable starting compositions. In Bilski, the Supreme Court concluded that § 273(a)(3) and its definition of “method” as including “a method of doing or conducting business” demonstrated that Congress did not view business methods as categorically ineligible for patenting. Section 103(b) similarly confirms that Congress viewed “nucleotide sequences” as appropriate subjects for patents; at minimum, it shows that Congress knows how to legislate in this area. Accord 141 Cong. Rec. S15220, S15222 (Oct. 17, 1995) (statement of Sen. Hatch) (“[t]he U.S. patent on the starting materials—typically a new DNA molecule, a genetically altered host cell, or a vector—can prevent others from using them in the United States in any way”).

In short, an isolated BRCA DNA molecule is a “composition of matter” by any understanding, and satisfies § 101.

B. Isolated DNA Molecules Do Not Fall Within The Three Judge- Made Exceptions To § 101

“The [Supreme] Court’s precedents provide three specific exceptions to § 101’s broad patent-eligibility principles: ‘laws of nature, physical phenomena, and abstract ideas.’” Bilski (quoting Chakrabarty). “[T]hese exceptions are not required by the statutory text,” but “they are consistent with the notion that a patentable process must be ‘new and useful.’ . . . The concepts covered by these exceptions are ‘part of the storehouse of knowledge of all men . . . free to all men and reserved exclusively to none.’” Id. (quoting Funk Bros. Seed Co. v. Kalo Inoculant Co.). As Bilski demonstrates, the touchstones of the three non-textual exceptions to patent eligibility are novelty and utility. Isolated BRCA DNA molecules fall within none of these three judicially created exceptions. They are not “laws of nature” like gravity or E=mc2, nor are they “physical phenomena” like electricity, nor are they abstract ideas like Bilski’s method of hedging in a commodity market. Rather, these isolated molecules are new chemical compositions, which were unavailable to the public until these inventors discovered and isolated them. They did not cease to be patent-eligible compositions of matter simply because one characteristic of an isolated DNA molecule is (in the words of the district court) a “physical embodiment of genetic information.”

C. “Products Of Nature” Are Not Categorically Ineligible For Patenting The district court believed that “products of nature” are categorically

excluded from “patentable subject matter under § 101,” and bottomed its rejection of Myriad’s isolated DNA molecules upon its application of that supposed exception. This ruling reflected an erroneous understanding of Supreme Court precedent.

1. “Products Of Nature” Is Not One Of The “Three Specific Exceptions” To § 101: Most simply, “products of nature” are not one of the narrowly cabined “three specific exceptions to § 101’s broad patent-eligibility principles” set forth by the Supreme Court. “[T]he Judiciary [does not have] carte blanche to impose other limitations that are inconsistent with the text and the statute’s purpose and design.” Bilski.

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2. A Sweeping “Products Of Nature” Exception Would Not Protect Valuable, New, And Useful Inventions: A sweeping exception to patent eligibility for “products of nature” would improperly exclude from patent protection truly “new” and truly “useful” discoveries, like pharmaceuticals derived from natural sources. Before the inventors performed the work resulting in the isolated BRCA1 and BRCA2 DNA molecules, those molecules did not exist. They were not naturally isolated by the body, and were unavailable (until the patented invention) to doctors and scientists for use as primers, probes, and for sequencing, in the detection and treatment of breast and other cancers. As the district court put it, “it is undisputed that the claimed compositions and methods possess utility.” Those useful molecules are true inventions, and until their invention they were not available to the public.

The decisions of this Court’s predecessor, which remain controlling precedent, compel the same conclusion. In re Bergy, (“a biologically pure culture produced by great labor in a laboratory and so claimed” is patent-eligible under § 101); In re Kratz, (claim to a “substantially purified” chemical composition naturally occurring in strawberries, 2-methyl-2-pentenoic acid, was patent-eligible “[s]ince the claims do not encompass natural compositions, in that ‘substantially pure’ 2M2PA does not apparently occur in nature”); In re Bergstrom, (“[W]hat appellants claim—pure PGE2 and PGE3 [prostaglandins]—is not ‘naturally occurring.’ Those compounds, as far as the record establishes, do not exist in nature in pure form, and appellants have neither merely discovered, nor claimed sufficiently broadly to encompass, what has previously existed in fact in nature’s storehouse, albeit unknown, or what has previously been known to exist.”). Indeed, the claimed molecules here are not only purified; they are chemically extracted (breaking their covalent bonds) and isolated from the native DNA as well, resulting in a new composition that is structurally and functionally different from native DNA.

3. Categorical Exclusion Of DNA Molecules From § 101 Would Disrespect Longstanding PTO Practice, A Long And Consistent Line Of Precedent, And Congress’s Proper Role In Making Patent Law: The court’s ruling that isolated BRCA DNA molecules are patent-ineligible “products of nature” gave insufficient respect to the PTO’s contrary determination, as well as to a long line of authority from this Court, its predecessor, and other respected jurists, holding that molecules that are newly isolated from natural products and useful are eligible for patents. Changes to such a longstanding practice should come from Congress, not the courts. This was exactly the modest judicial approach taken in J.E.M. Ag Supply, Inc. v. Pioneer Hi-Bred International, Inc., 534 U.S. 124 (2001), and echoed most recently in Bilski. In J.E.M. Ag Supply, the Supreme Court noted that § 101 has “broad scope and applicability,” and held that where a particular view of the statute’s applicability reflects a longstanding approach of the PTO and the courts, that view should be followed in the absence of any “indication from either Congress or agencies with expertise that such coverage is inconsistent with [the governing statutes].” Accord Bilski.

The district court gave this argument short shrift, misinterpreting Myriad’s position as one for “not engag[ing] the substance of Plaintiffs’ claims, but . . . instead dismiss[ing] them out of hand.” Yet it was the district court that refused to “engage

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the substance” of the PTO’s carefully considered Utility Examination Guidelines. These guidelines reflect not only an accurate summary of prior decisional law, but the PTO’s consistent practice of allowing patents, under § 101, on isolated DNA molecules: “A patent on a gene covers the isolated and purified gene but does not cover the gene as it occurs in nature.” 66 Fed. Reg. at 1093. In J.E.M. Ag Supply, the Supreme Court rejected the argument that plants were not within the scope of § 101 by noting “that the PTO has assigned utility patents for plants for at least 16 years and there has been no indication from either Congress or agencies with expertise that such coverage is inconsistent with [federal law].” 534 U.S. at 144-45. The Court further noted that the courts’ and the PTO’s practices had “led to the issuance of some 1,800 utility patents for plants,” and that “the PTO, which administers § 101 as well as the [Plant Patent Act], recognizes and regularly issues utility patents for plants.” Id. at 145.

The same salient facts are present here, and have engendered even greater public reliance. The PTO has granted utility patents for isolated DNA molecules for over 25 years. See, e.g., In re Kubin, (the patent claim at issue there, ultimately held obvious under § 103, claimed “a classic biotechnology invention—the isolation and sequencing of a human gene that encodes a particular domain of a protein”); Amgen Inc. v. Hoechst Marion Roussel, Inc., 314 (claim drawn to “non-naturally occurring” erythropoietin “avoids claiming specific subject matter that would be unpatentable under § 101.”); In re Deuel, 51 (reversing rejection of claims directed to a “purified and isolated DNA sequence”); Amgen, Inc. v. Chugai Pharm. Co., (upholding, against validity challenges, composition claims of U.S. Patent 4,703,008, issued on October 27, 1987, and directed to “a purified and isolated DNA sequence”); see generally Intervet Inc. v. Merial Ltd., (Dyk, J., dissenting in part) (“we have upheld the validity of several gene patents”).

Indeed, the Utility Examination Guidelines themselves have been in force for almost 10 years, and the longstanding agency practice reflected there has resulted in the issuance of more than 2,645 patents with claims to “isolated DNA,” and over 50,000 patents containing claims to a nucleic acid sequence. (See n.1, above.) In the face of that consistent agency and court practice, “there has been no indication from either congress or agencies with expertise that such coverage is inconsistent with” the patent statute. To the contrary, as set forth at pp. 32-33, above, § 103(b), which presumes that patents are available for “nucleotide sequences,” demonstrates that Congress thought that isolated DNA molecules are patent-eligible.

However, by refusing to give any consideration to this historical practice, and the significant industries built up in reliance thereon, the district court disregarded almost 100 years of precedent, dating back at least to Judge Learned Hand’s opinion in Parke-Davis & Co. v. H.K. Mulford Co. In the face of this consistent and long-followed view of § 101’s scope, plaintiffs’ arguments are better addressed to Congress, not to the courts. The Supreme Court has long held that courts “should not read into the patent laws limitations and conditions which the legislature has not expressed.” United States v. Dubilier Condenser Corp.

The district court erroneously dismissed all of this long-standing precedent on the ground that the cases involved questions of “novelty (a modern-day § 102 question), not of patentable subject matter (the § 101 question before this Court).”

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But Bilski—decided after the district court’s opinion—confirms that the questions of novelty and patent-eligible subject matter are inextricably intertwined, not “distinc[t],” as the district court thought. As Bilski emphasized, the non-textual exceptions to § 101’s broad applicability are “consistent with the notion that a patentable process must be ‘new and useful.’” 130 S. Ct. at 3225. That principle explains the Funk Brothers dictum on which the district court relied—matters covered by the three non-textual exceptions are not “new,” but “‘part of the storehouse of knowledge of all men . . . free to all men and reserved exclusively to none.’” Id. at 3225 (quoting Funk Bros.).

4. The District Court Misread Supreme Court Precedent As Supporting A Broad Exclusion Of “Products Of Nature” From § 101: The district court misread Chakrabarty and Funk Brothers as supporting a broad exclusion of “products of nature” from patent eligibility. The district court erroneously divined from Chakrabarty a legal standard requiring a claimed invention to be “markedly different” from a naturally occurring product in order to be patent-eligible, and applied that new standard in a sweeping, subjective manner that ignored the numerous, significant differences between isolated BRCA1 and BRCA2 DNA molecules and native DNA.

Chakrabarty did not pronounce or apply a legal standard that an invention must be “markedly different” from a naturally occurring substance in order to be patent-eligible. Rather, the Court used “markedly different characteristics” to describe the factual “contrast” between the particular bacterium in that case and the mixture of bacteria in Funk Brothers: “Here, by contrast, the patentee has produced a new bacterium with markedly different characteristics from any found in nature and one having the potential for significant utility.” 447 U.S. at 310. The proper legal standard under § 101 appears earlier in the opinion: “a nonnaturally occurring manufacture or composition of matter—a product of human ingenuity ‘having a distinctive name, character and use.’” Id. at 309-10 (citation omitted). Accord In re Kratz, (“the natural composition must inherently contain the [claimed] naturally occurring compound” and the claim must be so broad that it “encompass[es] both the known natural composition and the [claimed] naturally occurring compound” before it will be rejected). Under that standard, as shown above at pp. 35-36, and below at pp. 47-48, the isolated DNA molecule is plainly patent-eligible.

The “markedly different characteristics” identified by the Court confirmed that the organism was indeed “new,” but the opinion contains no statement or implication that the adverbial phrase “markedly different characteristics” was meant to create a new test for patent eligibility. For one, the phrase appears nowhere else in Supreme Court precedent or elsewhere in Chakrabarty itself. For another, it was unnecessary to resolving the case. But most tellingly, the term “markedly” was wholly unexplained in the opinion. Such a loose phrase, especially without further definition, invites litigants and judges to make their own subjective decisions about how different is “markedly” different. “Markedly different” is a fine term for judges to use when describing the particular facts of a particular case, as in Chakrabarty, but it surely was not meant as a legal standard to govern all future cases decided under the statute. As shown at pp. 50-52, below, the district court

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here freely applied that dubious standard by dismissing all the factual showings about the substantial differences between isolated BRCA DNA molecules and native DNA, instead concluding as a matter of law that the isolated molecules were not “markedly different.”

The court misread Funk Brothers as standing for the same proposition. The patent there claimed a product—“[a]n inoculant for leguminous plants” made up of “a plurality of selected . . . strains of different species of bacteria of the genus Rhizobium.” 333 U.S. at 128 n.1 (quoting claim 4). The Funk Brothers district court thought that “invention was not achieved” by mixing preexisting, commercially available strains of bacteria, and thereby invalidated the claims “because they did not involve invention or discovery of any new or useful art.” Kalo Inoculant Co. v. Funk Bros. Seed Co., (summarizing district-court holding). This holding of lack of “invention” did not address patent-eligibility under present § 101; rather, “invention,” under the pre- 1952 Patent Act, was the equivalent of “nonobviousness” under current § 103. See, e.g., Dann v. Johnston, (“As a judicial test, ‘invention,’ i.e., an exercise of the inventive faculty, has long been regarded as an absolute prerequisite to patentability. However, it was only in 1952 that Congress, in the interest of ‘uniformity and definiteness,’ articulated the requirement in a statute, framing it as a requirement of ‘nonobviousness.’”).

The Seventh Circuit reversed the Funk Brothers district court, finding that the claims possessed “inventive conception.” The Supreme Court then reversed the Seventh Circuit. In an opinion by Justice Douglas, the Court agreed with the district court’s conclusion and held that “the product claims do not disclose an invention or discovery within the meaning of the patent statutes.” 333 U.S. at 132 (citing Cuno Eng’g Corp. v. Automatic Devices Corp., another pre-1952 Act “invention” (obviousness) case). There was no dispute in Funk Brothers that the combination of bacteria was a patent-eligible “composition of matter”; instead, the claims were struck down for what is now obviousness under § 103.

The Funk Brothers opinion did refer to principles of patent eligibility, but only to explain the reasoning behind its obviousness determination. As Justice Douglas repeatedly explained, the only way the Court could view the inventor’s work as passing from the realm of ordinary skill to that of “invention” would have been to view the inhibitive or non-inhibitive properties of the selected bacteria as a patentable invention, since claim 4 was not limited to mixtures of any particular strains—rather, it claimed broadly all mixtures that had the desired properties: “[T]here is no invention here unless the discovery that certain strains of the several species of these bacteria are non-inhibitive and may thus be safely mixed is invention.” 333 U.S. at 132; see also id. at 130; id. at 133-34 (Frankfurter, J., concurring) (noting that the claims were so broad as to cover any composite culture possessing that natural effect, not just mixtures of the particular strains the inventor had discovered). The combination was thus ruled obvious.

The analogy chosen by Judge Dyk in his separate opinion in Intervet illustrates the important differences between Funk Brothers and this case. There, Judge Dyk suggested that “[i]t would be difficult to argue, for instance, that one could patent the leaves of a plant merely because the leaves do not occur in nature in their isolated form.” (Dyk, J., dissenting in part). Those leaves, however, would

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likely fail under §§ 102 or 103, because the mere plucking of leaves would not invent a new product or constitute a nonobvious “invention.” Or it might fail under the logic of Funk Brothers, because the plucked leaf would have exactly the same properties as the unplucked leaf— unlike here, where isolated DNA molecules possess significantly different structural and functional characteristics from native DNA. In the words of Chakrabarty, the picked leaves would not be “a product of human ingenuity,” because one of ordinary skill would be able to pluck the leaf off of the previously known plant. See also Ex parte Latimer.

Isolated DNA molecules are “products of human ingenuity” and thus fall comfortably within any definition of “invention.” (Again, it bears noting that plaintiffs only challenge Myriad’s patent claims under § 101, not §§ 102 or 103, and their utility is undisputed.) These inventors’ work yielded a new composition of matter with substantial societal benefit, which added to the body of human knowledge. That is enough to demonstrate that these compositions of matter are patent-eligible under § 101.

5. A Categorical “Products Of Nature” Exception Would Be Inconsistent With The Statute And Unworkable: A sweeping exception for “products of nature” would be at odds with cases such as Chakrabarty and J.E.M. Ag Supply, which upheld patents on living organisms and seeds, respectively. Further, such an exception would be impossible to administer from a judicial perspective—at some level, every composition of matter is a composition of natural materials, and a sweeping “products of nature” exception could potentially make patent-ineligible a wide range of truly new and useful inventions, from the purified extract of a naturally occurring plant (e.g., the cancer-fighting drug Taxol, an extract from the Pacific Yew tree) to the new and useful combination of two or more naturally occurring substances, to the potentially life-saving isolated DNA molecules at issue here. As the Supreme Court recognized in Diamond v. Diehr, “[t]o accept th[is] analysis . . . would, if carried to its extreme, make all inventions unpatentable because all inventions can be reduced to underlying principles of nature which, once known, make their implementation obvious.” 450 U.S. 175, 189 n.12 (1981). See also Merck & Co. v. Olin Mathieson Chem. Corp. (“All of the tangible things with which man deals and for which patent protection is granted are products of nature in the sense that nature provides the basic source materials.”).

These principles explain the dictum from Chakrabarty on which plaintiffs and the district court have relied in claiming a “products of nature” exception to § 101. There, the Court upheld as patent-eligible the applicant’s claim to a microorganism, noting that his claim was drawn “to a nonnaturally occurring manufacture or composition of matter—a product of human ingenuity ‘having a distinctive name, character and use.’” 447 U.S. at 309-10 (quoting Hartranft v. Wiegmann). Here, the isolated DNA claimed in the Myriad patents is “a nonnaturally occurring manufacture or composition of matter”—in the form claimed in the patents, the isolated BRCA1 and BRCA2 molecules are “nonnaturally occurring” and exist only because of “human ingenuity” in discovering and isolating them. These isolated molecules also have a “distinctive name,” and their “character and use” are unlike any found in nature: Their distinctive character allows them to be used in distinctive ways—e.g., as probes and primers, and in the diagnosis and treatment of cancers.

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See also Dolbear v. Am. Bell Tel. Co. (While “electricity, one of the forces of nature, is employed” in the telephone, electricity, left to itself, will not do what is wanted. The art consists in so controlling the force as to make it accomplish the purpose.”). These compositions are human inventions that, by their patenting, have added significantly to human knowledge, and “promote[d] the Progress of Science and useful Arts.”

These principles also distinguish the other decisions on which the district court relied. In American Wood-Paper Co. v. Fibre Disintegrating Co., the Court rejected a manufacture claim drawn to cellulose extracted from vegetable substances, because “[p]aper-pulp obtained from various vegetable substances was in common use before the original patent was granted to Watt & Burgess, and whatever may be said of their process for obtaining it, the product was in no sense new.” Id. at 596. However, “had [it] not been introduced to the public, the Watt & Burgess product might have been patented as a new manufacture.” Id. In Cochrane v. Badische Anilin & Soda Fabrik, the Court rejected a product patent where the “artificial” alizarine dye, though produced by a different process, was the same substance that had long been isolated from madder root by dyers: “It was an old article. . . . Calling it artificial alizarine did not make it a new composition of matter, and patentable as such.” Id. at 311. In American Fruit Growers, Inc. v. Brogdex Co. the Court concluded that the addition of a small amount of borax to the rind of a fresh orange did not meet the definition of a “manufacture,” because the dictionary definition of that term required the creation of “an article for use which possesses a new or distinctive form, quality, or property.” Id. at 11. The orange at issue was not a “manufacture,” in the Court’s view, because “[t]here is no change in the name, appearance, or general character of the fruit. It remains a fresh orange, fit only for the same beneficial uses as theretofore.” Id. at 12. As Bilski underscored, the patent laws are appropriately concerned that the exclusive rights granted in a U.S. patent are not used to monopolize old, preexisting matter. But, an ersatz “products-of-nature” exception to patent eligibility is too blunt a tool for sorting true, patent-eligible invention from old natural phenomena. Other portions of the Patent Act—§ 101’s utility requirement, § 102 (anticipation), § 103 (obviousness), and § 112 (written description)—provide finer, more appropriate filters for separating truly inventive additions to human knowledge from unpatentable matter. Id. at 3225; In re Bergy; see generally Dan L. Burk & Mark A. Lemley, Policy Levers in Patent Law.

In sum: The BRCA1 and BRCA2 molecules were not old matter when they were isolated from native DNA. The work of the inventors in this case constituted invention of a new composition of matter, or certainly an “improvement thereon,” which added greatly to human knowledge. Under § 101, these new compositions are patent-eligible.

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READINGS GROUP 3: American Medical Association (AMA) Source: http://digitalcommons.wcl.american.edu/cgi/viewcontent.cgi?article=1003&context=pub_disc_briefs&sei-redir=1#search=%22amici+curae+medica+associations+against+BRCA%22

Link accessed March 30, 2011. Preliminary Statement: The U.S. Constitution, Article 1, Section 8, Clause 8 and the Patent Act 35 U.S.C. § 101 et seq., limit the reach of the patent system by deeming certain categories of inventions patent eligible and prohibiting patents for certain discoveries, most notably products of nature and laws of nature. In this case, Myriad’s patents claim products of nature (gene sequences) and laws of nature (correlations between the existence of a mutation and the likelihood of developing cancer or between an affected tumor sample and normal tissue). They should be invalidated. (…)

Myriad’s Breast Cancer Genetic Sequence and Correlation Patents. Everyone has at least two genes related to breast cancer in his or her body

(known as BRCA1 and BRCA2). These genes have sequences that consist of a long string of the bases A, T, C, and G. BRCA1 has 81,154 bases and BRCA2 has 84,188 bases. There are hundreds of possible naturally occurring mutations (variations) in the BRCA1 and BRCA2 DNA sequences. Some people have DNA sequences in their BRCA1 and BRCA2 genes that do not predispose them to breast cancer and/or ovarian cancer, and some people have mutations in the sequences that do predispose them to such cancers.

Shortly after a collaborative international Consortium of scientists had located the BRCA1 gene on chromosome 17 (of the 23 human chromosomes) and was engaged in determining its various DNA sequences, a University of Utah scientist who was part of the public consortium created Myriad to commercialize the gene once it was fully sequenced. (…). Myriad’s assignor patented the naturally occurring sequences for BRCA1 and for BRCA2 (the “sequence claims”), as well as the act of looking at a person’s breast cancer gene sequence and comparing it to a known sequence (the “correlation claims”).(…) Of course, because Myriad’s patents are for “isolated DNA” or “isolated DNA molecules” and for performing the mental process of “comparing” sequences, they do not prohibit people from having such sequences or information in their bodies. Rather, they prohibit people from doing anything with their DNA once it is removed from their bodies, and from doing anything useful with the genetic sequence information that such DNA contains once it is identified, even if it is identified by methods and processes that are not patented by Myriad. Further, because the patents apply to any isolated BRCA1 or BRCA2 molecule, they prevent anyone from simply removing such DNA from a person’s body (since that would result in “isolated DNA”) or analyzing a person’s DNA gene sequence (since that would involve the use of “isolated DNA”). The correlation patents prohibit using such sequence information to diagnose disease, even if anyone could obtain the sequence information without violating Myriad’s sequence patents. If that were not enough, Myriad’s sequence patents prohibit research with

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any isolated natural DNA and some of the patents prohibit even thinking about those sequences for research or medical diagnosis and treatment.

Specifically, Myriad obtained a patent covering any “isolated DNA” having a sequence “coding for a BRCA1 polypeptide” (i.e. coding for that protein) or “at least 15 nucleotides” (DNA bases) of that sequence (claims 1 and 5 of U.S. Patent No. 5,747,282). Similarly, Myriad obtained a patent covering any “isolated DNA molecule” having a sequence “coding for a BRCA2 polypeptide” or having any “mutated form” associated with susceptibility to cancer (claims 1 and 6 of U.S. Patent No. 5,837,492). These patents cover naturally occurring genes removed from the cell and prevent all uses of the information the genes contain. Myriad has also obtained a patent on simply “analyzing a sequence”; its patent covers any method or technology for “detecting” certain mutations (“germline alteration”) in the BRCA1 gene of any “human sample” of DNA, mRNA, or cDNA (Claim 1 of U.S. Patent No. 5,709,999). Although Myriad did not develop new methods or technology for this analysis, its improperly issued patents prevent others from using any method or technology to detect these mutations in the BRCA1 gene. Further, Myriad has obtained patents on the act of “comparing” a person’s breast cancer gene sequence to the normal (“wild-type”) BRCA2 gene sequence. If the sequences are different, the patient’s gene is a “mutant” gene which “indicates” a predisposition to cancer (Claim 1 and 2 of U.S. Patent No. 6,033,857). These patents prohibit others from performing the simple mental step of comparing gene sequence information. The scope of Myriad’s patent portfolio must be fully appreciated. By staking claims on all isolated versions of the BRCA1 and BRCA2 genes, Myriad effectively controls all of the naturally occurring BRCA1 and BRCA2 breast cancer genes from everyone’s bodies. No woman (or man) can give her (or his) own breast cancer gene to a doctor or researcher to analyze for purposes of diagnosis or research, because once that gene is removed from the body Myriad’s patent claims cover it. No clinician or scientist can perform diagnosis or research using such gene sequences or the information they contain without violating the patents.

Adverse Effects of Myriad’s Patents and Similar Genetic Patents. Myriad’s patents, and patents owned by other companies, universities, and

individuals, on genetic sequences and biological correlations have serious adverse impacts on Amici and the public that they serve. These patents hamper medical discovery and innovation, interfere with the practice of medicine, and harm patients. For 20 years from the date of the filing of the patent application (and sometimes longer), a patent holder controls any use of its invention and can prevent anyone else from using, making, selling, or importing the invention. 35 U.S.C. §§ 154, 271(a) (2009). This ability to control all uses of an invention makes sense for a machine, such as a gene sequencer, but not for the molecule containing the gene sequence itself, which is not merely a tangible entity, but also the information code of the human body. There is no way to “design around” these patents. Given that there are no substitutes for analyzing a patient’s genetic makeup, the patent holder possesses a broad and unavoidable monopoly in the market for medical research, medical services, and patient care. Upstream of the end users and the market, the patent holder can prevent scientists and clinicians from undertaking research on the genetic disease related to that gene and from developing improved diagnostic

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procedures, tests, and equipment. The patent holder can charge an excessive royalty for even an inferior genetic test. Such patents prevent doctors from properly diagnosing even those patients willing and able to pay the excessive costs. The patents additionally interfere with medical care because Myriad does not look for every known or possible mutation in the breast cancer gene. [AMA] [is] very concerned that exclusivity over the use of the BRCA1 and BRCA2 sequences, and the consequent exclusive right to perform breast cancer genetic testing, has led to the misdiagnosis of patients and has precluded the deployment of improved genetic tests. (Tom Walsh et al., Spectrum of Mutations in BRCA1, BRCA2, CHEK2, and TP53 in Families at High Risk of Breast Cancer, 295 JAMA 1379-1388 (2006): 12% of the 300 people examined from high risk families had mutations the Myriad testing missed). Because Myriad has exclusive use of the breast cancer gene sequences, moreover, no woman can get an independent second opinion about her condition before deciding to have her healthy breasts or ovaries removed in order to avoid cancer. As a result, women may have their breasts or ovaries removed unnecessarily when they received a false positive on a BRCA1 or BRCA2 test because they do not have access to an independent confirmatory test. (…) Because of its patents, Myriad can preclude all others from looking at a person’s BRCA1 and BRCA2 breast cancer gene sequences to determine if she has a mutation related to cancer. With the monopoly its patents provide, Myriad charges over $3000 per test, substantially more than the cost of those tests and consequently substantially more than competitors would charge. In 2008, Myriad spent $32,340,000 to perform molecular diagnostic tests, and had revenue for its tests totaling $222,855,000. (…) In Ontario, Canada, where the regional public healthcare plan is ignoring Myriad’s patent, the testing for breast cancer is performed for a third of what it costs when done by Myriad. CBC News, Ontario to Offer New Genetic Test for Breast, Ovarian Cancer (Jan. 8, 2003), available at:

http://www.cbc.ca/health/story/2003/01/06/test_genetic030106.html. The problems with genetic sequence and correlation patents extend far beyond Myriad’s patents on breast cancer genes. For example, when a company obtained a patent on the hepatitis C genome, it was able to prevent other companies from offering inexpensive public health screening for hepatitis C, because the patent allowed it to, in essence, “own” the disease. (…) The health consequences of failing to diagnose and treat hepatitis C are serious, not only for the infected patient but for others whom that person may unknowingly infect. Patents on gene sequences have also resulted in people’s deaths. Long QT syndrome is a disorder of the heart’s electrical system that is characterized by irregular heart rhythms and a risk of sudden death. A gene associated with Long QT was patented and assigned to the University of Utah Research Foundation. U.S. Patent No. 6,207,383. The company with the exclusive license to the Long QT sequence went through corporate upheavals. For a two year period, the licensee did not offer diagnostic testing for Long QT syndrome. Other laboratories had the capability and willingness to offer the test, but were forbidden to do so by the patent licensee. During this period at least one patient, age 10, died from her undiagnosed Long QT syndrome; her death could have been prevented had testing been available. (…)

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In addition to impeding appropriate health care, the Myriad patents and similar patents related to other diseases deter medical innovation. Breast cancer researchers have been prevented by Myriad from undertaking their research. (…) A survey of members of Amicus American Society of Human Genetics found that 49% have had to limit their research due to gene patents. (Issac Rabino, How Human Geneticists in U.S. View Commercialization of the Human Genome Project, 29 Nature Genetics 15-16 (2001).

As increasingly more medical knowledge depends on an understanding of underlying genetic processes, continued patenting of genes (or enforcement of such gene patents) will likely result in significant stifling of medical research in multiple disease processes. See, e.g., Patents, Medicine, and the Interests of Patients, 109 Obstet. Gynecol. 1249-53 (2007) (Am. Coll. of Obstet. & Gynecol. Comm. Op. No. 364). As the understanding of the genetics of ovarian and related cancers expands, it has become apparent that knowledge of DNA mutation status is critical to understanding the results of therapeutic trials in ovarian cancer, as well as to appropriately caring for the participants in these trials and their family members. Clinical genetic testing for BRCA1 and BRCA2 mutations through Myriad is prohibitively expensive in all but the most well-funded trials. Research testing is occasionally available, but more frequently is not performed because of the chilling effect of Myriad’s patents. Even when research testing is available, it remains suboptimal due to Myriad’s prohibition of sharing the test results with the research participants and their families, placing researchers in an ethically untenable position. Soon technology will allow the sequencing of a person’s entire genome of 25,000 genes for $1000. (…) Adding even a seemingly modest royalty cost of $100 per gene would total an unaffordable $2,501,000 per test. Spending money on licenses for patents that are invalid and should never have been issued also diverts needed money from healthcare and research.

Myriad has manifested a clear intent to enforce its patent rights, and clinicians and researchers have therefore avoided infringement to the detriment of medical care and innovation. Even Myriad recognizes the breadth and adverse consequences of its patent portfolio and aggressive litigation posture. Although the testing of the BRCA1 and BRCA2 sequences performed by Myriad does not cover all mutations, a Myriad official stated that the use of a new technology to identify mutations in a patient that Myriad missed “would probably infringe on our patents.” Erik Stockstad, Genetic Screen Misses Mutations in Women at High Risk of Breast Cancer, 311 Science 1847 (2006).

ARGUMENT I. Gene Sequences and Correlation Claims Are Not Patentable Inventions Within the Meaning of Article I, Section 8, Clause 8 of the U.S. Constitution and 35 U.S.C. § 101

The U.S. Constitution grants Congress the power “to promote the progress of Science and the useful Arts, by securing for limited Times to Authors and Inventors the exclusive Right to their respective Writings and Discoveries.” Art. I, § 8, cl. 8. However, genetic sequences and mental correlations are not “Discoveries” of “Inventors” as these terms are used in the Constitution. Accordingly, Congress could

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not authorize and has not authorized patents for them in 35 U.S.C. § 101. Rather, they are unpatentable products of nature and laws of nature. The term “Discoveries” in the Constitution has a special meaning, and is synonymous with the modern term “inventions” in the restrictive sense of a human, physical creation or process. Writing in 1889, a patent law scholar noted that someone “may invent a machine, and may discover an island or law of nature. For doing the first of these things, the patent laws may reward him, because he is an inventor in doing it; but those laws cannot reward him for doing either of the others, because he is not an inventor in doing either.” (…) The distinction between a patentable invention of biotechnology and an unpatentable natural discovery is illustrated by the seminal 1980 Supreme Court case that first authorized patents on inventions using life forms. That case involved a man-made (genetically engineered) bacterium, which the court carefully described as not naturally occurring. The Court stated:

The laws of nature, physical phenomena, and abstract ideas have been held not patentable. Thus, a new mineral discovered in the earth or a new plant found in the wild is not patentable subject matter. Likewise, Einstein could not patent his celebrated law that E=mc2; nor could Newton have patented the law of gravity. Such discoveries are “manifestations of . . . nature, free to all men and reserved exclusively to none….” Similarly, the physiological fact that a naturally occurring mutation correlates to a disease is a law of nature like gravity. Such discoveries are “manifestations of . . . nature, free to all men and reserved exclusively to none….” Here, by contrast, the patentee has produced a new bacterium with markedly different characteristics from any found in nature and one having the potential for significant utility. (…) To allow a patent on a gene “isolated” from the body is akin to allowing the

first surgeon who removed a kidney to patent any and all “isolated” kidneys. The holder of the patent on an isolated kidney could prevent other surgeons from removing (“isolating”) diseased kidneys. The patent holder could also use its exclusive rights to charge a royalty of $3,000 or more each time a person donated a kidney to a relative.

The question of patentable subject matter is not a question of usefulness, novelty or obviousness. A plant discovered in the wild or a formula like E = MC2

is

extremely useful, and may be novel in the sense of not having previously been known and may be non-obvious in the sense of requiring someone to think creatively to search for it. Yet they are not patentable, because products of nature and laws of nature are not human inventions; they must be “free to all men” so as to encourage innovation and to reward only actual inventors. (…)

Myriad has not invented the genes that existed naturally in people’s bodies; it has only removed them from those bodies and taken them out of the cellular material, using common, long-standing techniques. Nor has Myriad invented any chemical or mechanical methods of determining whether there is a mutation in a breast cancer gene. Rather, what the patentee claims to have discovered are pre-existing genetic sequences and a natural relationship (correlation) between certain mutations and breast cancer. Patenting this discovery also effectively gives Myriad

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control over all previously and subsequently discovered means of testing for inheritable BRCA1 and BRCA2 breast cancer mutations. Further, the relationship between gene mutations and breast cancer patented by Myriad is a law of nature that exists independent of human intervention, invention, or manipulation. This relationship existed long before it was discovered, and is neither new nor an invention, but only an existing natural phenomenon. (…) Nor was the incentive provided by the patents necessary to lead to the discovery of the BRCA1 and BRCA2 sequences. The international Breast Cancer Linkage Consortium was sequencing the genes in a cooperative effort and planned to make the sequences publicly available and not patent them. (…) Yet after the BRCA1 gene was localized by a different team in the Consortium in 1990, in 1991, Mark Skolnick, a member of the Consortium, founded Myriad Genetics in order to commercially exploit the research. Had he not done so, the discovery would still have occurred, but the results would have been free to all men and reserved exclusively to none.

A. Myriad’s Sequence Claims are Unpatentable Products of Nature

(…) Even though none of its claims use the term “synthesized,” Myriad is apparently trying to avoid application of the products of nature doctrine by asserting that it is entitled to patents on the BRCA1 and BRCA2 genes because it has “synthesize[d] DNA corresponding to the genes in test tubes.” (…) The process of synthesis, routinely done today by biology students, was not invented by Myriad but is merely a way to make a copy of a gene. (…) This is not patentable invention. (…)

Under the U.S. Constitution and 35 U.S.C. § 101, isolated and purified genetic sequences are unpatentable. The mere fact of isolation and purification is not enough of a change, as the products do not have any functions that they did not have already. Similarly, “synthetic” genetic sequences that are not materially different from their naturally occurring counterparts are not patentable inventions. Myriad’s patent claims to DNA molecules and gene sequences should be invalidated.

B. Myriad’s Correlation Claims are Unpatentable Laws of Nature

The U.S. Supreme Court has consistently held that laws of nature are not patentable. “This Court has undoubtedly recognized limits to § 101 and every discovery is not embraced within the statutory terms. Excluded from such patent protection are laws of nature, natural phenomena, and abstract ideas.” (…) A newly-discovered phenomenon of nature, moreover, must be “treated as though it were a familiar part of the prior art” and free for all to use. (…) Myriad’s discovery of a relationship that has always existed between certain mutations and breast cancer is not patentable – and thus there is simply no invention left over for Myriad to patent. (…)

The U.S. Court of Appeals for the Federal Circuit in In re Bilski has reiterated that the machine-or-transformation test must be passed in order for there to be a patent-eligible invention. (…) But Myriad’s claims (1) do not include the use of any particular machines and (2) do not transform an article to a different state or thing.

Five of Myriad’s correlation claims, moreover, involve only one step – “comparing” two types of information, the sequence of the patient and a known

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sequence. Claim 1 of U.S. Pat. No. 5,709,999, Claim 1 of U.S. Pat. No. 5,710,001, Claim 1 of U.S. Pat. No. 5,753,441, Claims 1 and 2 of U.S. Pat. No. 6,033,857. These claims do not recite the use of a particular machine, and the claimed comparison can be performed mentally by simply using the sequence disclosed in the patent, defeating the quid-pro-quo of the patent grant (the ability of the public and other inventors to use information about the patented invention) even assuming such claims were eligible.(…) These claims do not even recite the steps (however performed) of obtaining the information for comparison, and thus cover solely the mental act of recognizing a similarity or a difference.

(…) Myriad has patented any and all uses of the law of nature that certain mutations are correlated with breast cancer. This overcompensates Myriad by granting rights to dominate all subsequent inventions that would use that correlation, a biological fact that Myriad did not itself invent and which thus should be free for all to us.

II. Patents on Products of Nature and Laws of Nature Violate Medical and

Scientific Ethical Tenets and Are Not Necessary to Promote Innovation (…) AMA’s Ethics Opinion 9.095 states, “The use of patents, trade secrets, confidentiality agreements, or other means to limit the availability of medical procedures places significant limitation on the dissemination of medical knowledge, and is therefore unethical.” (American Medical Association, Opinion 9.095 – The Use of Patents and Other Means to Limit Availability of Medical Procedures, (adopted June 1995), available at http://www.ama-assn.org/ama/pub/physician-resources/medical-ethics/code-medical-ethics/opinion9095.shtml.) (…) Additionally, “[b]ecause a patent claiming a gene as a composition of matter enables a patent holder to control future applications of the patented gene or sequence, such patents should not be granted.” Id. Like doctors, scientists also have long-standing, historically recognized duties to freely disseminate their discoveries of products of nature and laws of nature and not to subject those discoveries to private property rights. (…) The scientists’ ethical duty remains enshrined in the patent law to this day, because such natural discoveries must be treated as prior art and thus are not patentable. Moreover, there is no need to provide patent incentives to health care professionals, clinicians, and scientists to discover and study gene sequences and the correlations at issue in this case. Indeed, a recent report by the Secretary of Health and Human Service’s Advisory Committee on Genetics found that patents “do not serve as powerful incentives for either genetics research in the diagnostic arena or the development of genetic tests.” (…) Various members of (…) medical organizations are willing to identify gene sequences and correlations without patenting them, and there was no shortage of researchers who were trying to sequence the breast cancer genes without the desire to patent those sequences.

Public money – rather than private money – has been the engine for discovery of the genes at issue, as well as most human genes. A publicly-funded Consortium did most of the work to identify the BRCA1 and BRCA2 genes. Moreover, Myriad’s patents’ assignor utilized over $5 million of taxpayer money in the form of a direct grant from the National Institute of Health to sequence the BRCA1 gene. (…) A federal researcher for the National Institute of Environmental Health Sciences

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(NIEHS) in North Carolina also aided Myriad in its work. (…) The public thus has paid for the work underlying Myriad’s patents, yet will pay hundreds of millions of dollars more in royalties each year because of the patents at issue here. Moreover, the research occurred within the Human Genome Project – an international multi-government and private-sector funded effort that placed other sequences in the public domain, where they belong. (…)

Patents on genes and on the correlation between mutations and disease in general, and Myriad’s patents in particular, thwart rather than promote innovation. Patent law is supposed to be a bargain in which the patent holder gets a time-limited exclusive right to make, use, or sell a claimed invention of proportional scope to the inventive contribution to the field, in exchange for publishing in the patent the description of the invention that all can use to further develop the frontiers of science and technology. (…) However, the system breaks down when a patent is granted for preexisting natural phenomenon or the information disclosed by the patent itself – such as the sequence of a gene. Then the patent holder has a right to prevent others from using the disclosed information entirely.

The Myriad patents deter innovation because any new testing or treatment technology must rely on the natural materials and biological facts that were not created by Myriad but were patented by its assignor – the BRCA1 and BRCA2 genes in all of their forms, the information in the sequences that they contain, and the fact that certain BRCA1 and BRCA2 gene sequences are correlated with breast cancer.

CONCLUSION Upholding the sequence claims and correlation claims at issue here would conflict with long-standing patent jurisprudence and would continue to thwart, not promote, “the Progress of Science and the useful Arts.” This Court should follow the 150-year-long precedents of the U.S. Supreme Court that one cannot patent “laws of nature, natural phenomena, and abstract ideas.”(…) Such a holding is in keeping with the professional and ethical tenets of medicine and reflects the long-standing ethics of science. The patent claims at issue in this case deter the [AMA] from offering the best quality and most accessible health care to their patients. It is crucial to patient care and to medical research that natural biological materials and basic scientific information be allowed to be shared, analyzed, and used in an unfettered way.

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READING GROUP 4: Center for Genetics and Society (CGS) Source: http://www.biopoliticaltimes.org/article.php?id=4901

1. Human genes and their relationships with phenotypic characteristics are not patentable because they are products and laws of nature, respectively.

2. Such patents harm people by hindering health access and medical research. The patent at the center of the lawsuit covers genes associated with breast and ovarian cancer; these patents are particularly problematic for women’s health.

3. The human genome is the common heritage of humanity, and thus part of the public domain.

Argument: Competition between public group and private company. 1. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1070823/

The US biotechnology company Celera Genomics has announced that it has the

DNA sequence of 90% of the human genome in its databases, far outpacing both its own schedule and that of the publicly funded Human Genome Project, which was established in 1990. Celera, founded in May 1998 by Craig Venter, claims to have sequenced 81% of the genome on its own. It has inferred an additional 9% from the publicly available data published by the National Institutes of Health in Bethesda, Maryland and by the Sanger Centre in Cambridge, England. The company estimates that 97% of all human genes are already represented in its database, given a genome size of about 80,000 genes.

Celera, which began its sequencing project in September of 1999, expects to complete the entire sequence by June of 2000. The achievement, which ushers in the era of pharmacogenomics, is remarkable for its rapid pace and has widespread medical, ethical, and financial implications, especially because Celera is a private commercial enterprise.

The Human Genome Project is being conducted by eight university centers funded by the National Institutes of Health, and by the US Department of Energy and the Sanger Centre in Cambridge, England.

Celera takes a different sequencing approach from that of the public consortium. Celera uses a “shotgun” technique, whereby the DNA of a single anonymous male is sheared into many small and large fragments, which are then reassembled like one puts together a large jigsaw puzzle. This is accomplished by inserting the fragments into a plasmid vector and propagating them in Escherichia coli to produce millions of copies of each fragment. Linking DNA sequences of known length are added to fill in the gaps. When missing pieces are found, the linkers can be deleted. The millions of DNA base pairs are then reassembled with

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the help of a supercomputer. Celera's computer is believed to be the second most powerful in the world and is active 24 hours a day, 7 days a week. Two billion base pairs are sequenced by the Celera computer each month.

In contrast, the Human Genome Project is sequencing the DNA of multiple anonymous donors and mapping the genes to a precise location in a more painstaking manner. Their protocol entails inserting the genes into bacterial artificial chromosomes, mapping their positions on these chromosomes, and then sequencing them. The Celera approach skips the mapping and the use of bacterial artificial chromosomes, which can hold on average only 150,000 DNA bases each. Furthermore, Celera benefits from the publication by the Human Genome Project of all newly sequenced DNA fragments on its website. Under the Bermuda Agreement, the public consortium is obliged to publish newly sequenced genes onto a publicly accessible website within 24 hours. Celera is not bound by such constraints, but takes advantage of them. Because Celera is a commercial enterprise and is obtaining patents for many of the genes that it is discovering, interesting medical and ethical questions arise. The concern has been raised that the success of Celera will lead to decreased federal funding for the public initiative.

The consortium's project is important because the data are free and available to everyone, whereas Celera may choose to withhold some information, particularly that related to genetic polymorphisms, which often disclose information about genes related to certain diseases. More worrisome is the proprietary use of the human genome. Venter has stated that he will eventually make the basic genome widely available but will sell gene sequences related to certain diseases to various pharmaceutical companies and to subscribers to its genome database. Academics and universities will be allowed to subscribe at reduced prices. Celera already has agreements with several blue chip pharmaceutical companies, including Pfizer, Novartis, and Rhône-Poulenc, to provide the gene sequences related to certain diseases. 2. http://www.the-american-interest.com/article-bd.cfm?piece=653

April 12, 1955 was a day of celebration. Across the United States, church bells rang, sirens blew, and people poured into the streets singing and dancing. The rejoicing was a spontaneous response to news that field trials of Jonas Salk’s vaccine against the dread polio virus had been successful. The public had avidly followed the search for a vaccine for years. Hundreds of thousands of volunteers had participated in the trials, and tens of millions contributed dimes, quarters and dollars to the effort. According to a 1954 Gallup poll, more Americans knew about the polio field trials than knew the full name of their President, Dwight David Eisenhower. On the day the field tests were pronounced a success, Edward R. Murrow interviewed Salk live on his television show See It Now. “Who owns the patent on this vaccine?” Murrow asked. “Well, the people, I would say”, Salk replied. “There is no patent. Could you patent the sun?”

What a difference a half century makes. Today, patent applications are a part of the research routine, especially in the life sciences. Pharmaceutical and biotechnology companies, universities and governments hold patents not just on

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vaccines and other drugs and devices critical to human health, but also on things once considered beyond the reach of property law. For example, in recent decades, patents have been granted on a menagerie of laboratory-created life forms, from microbes like the oil-eating bacterium at issue in a 1980 Supreme Court case to mammals like Harvard’s OncoMouse, genetically modified to be cancer-prone.

Human bodies have also become sources of materials that can be privately claimed and commercially exploited. A wide variety of human tissues and molecules have been ruled patentable. Most troubling to many are the patents that now bedeck the human genome. The U.S. Patent and Trademark Office (USPTO) has granted somewhere between 3,000 and 5,000 patents on human genes themselves, including those associated with Alzheimer’s disease, muscular dystrophy, colon cancer, asthma and many other illnesses. A 2005 study published in Science estimated that some 20 percent of all human genes had already been patented, 63 percent of them by private firms.

Though patents on human genes are strongly supported by the biotechnology industry and its financial backers, they make many basic researchers uneasy. For example, the Human Genome Project website points out that because U.S. patent applications must remain confidential for 18 months after filing, researchers who use genetic sequences “risk facing a future injunction if those sequences turn out to be patented by a private company.”

Patents confer a great deal of power. For 20 years (after which the protected inventions are supposed to enter the public domain), they give their holders the right to prevent anyone—including doctors, patients and other researchers—from studying or testing “their” genes. They control what research can be done on the genetic sequences themselves or any mutations of them, whether for commercial or other purposes. They can determine who can do diagnostic tests involving those genes, and—through royalties—affect how much the tests cost.

In contrast to the keen public interest in Dr. Salk’s pronouncement about the ownership of the polio vaccine, few Americans outside the biotechnology industry and specialized legal and business circles are aware of what the subtitle of a recent book by attorney and philosopher David Koepsell terms The Corporate Gold Rush to Patent Your Genes (2009). Many people are shocked to learn that exclusive rights to human genes can be assigned patents at all. There has been surprisingly little public discussion of the broad social and ethical concerns raised by gene patents, or of their concrete implications for health care and biomedical research. But that may be about to change.

In May, the half-million-member American Civil Liberties Union and the Public Patent Foundation of the Benjamin Cardozo School of Law at Yeshiva University filed a lawsuit that could turn gene patents into a public controversy and change the way many biotechnology companies do business. Most previous gene patent cases have involved a battle over ownership of a particular gene in which neither side has any incentive to question the gene’s patentability. However, this lawsuit challenges the validity and constitutionality of human gene patents in general, and specifically of two genes associated with a greatly increased risk of breast and ovarian cancer. Observers are already predicting that the case will eventually wind up before the Supreme Court, which has never directly ruled on the patentability of human genes.

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In addition to the USPTO, the lawsuit names Myriad Genetics, a private corporation, and the University of Utah Research Foundation, which together hold the patents on the breast cancer genes known as BRCA1 and BRCA2. Its twenty plaintiffs include four scientific organizations representing more than 150,000 researchers and laboratory professionals; two influential women’s health organizations, Breast Cancer Action and Our Bodies Ourselves; and individual researchers, genetic counselors and breast cancer patients.

The plaintiffs give several reasons for their challenge. Genetic scientists state that Myriad has directly prevented some of their work with cease-and-desist letters, and indirectly hindered other research because of the chilling effects of its aggressive patent patrolling. And because Myriad has exclusive control over the data it collects from its tests, it has the sole power to use—or to withhold from other researchers—a large set of data with significant implications for breast cancer research.

Several women’s health organizations say that Myriad has kept the cost of the test for BRCA1 and BRCA2 unreasonably high; priced at more than $3,000, some women who need it can’t afford it. Myriad’s monopoly also means that no one can develop additional tests on the genes. Breast Cancer Action says that some women get ambiguous results from Myriad’s test, but there is no alternative to it. Breast cancer patients and their female relatives point out that they can’t get second opinions about their particular genetic variants or the interpretation of them and are thus forced to make decisions about their health care with inadequate information.

These are some of the immediately tangible consequences of Myriad’s patents and the way the company has chosen to protect them. A lawsuit, of course, also turns on precedent and technical legal issues. The ACLU and Public Patent Foundation make three core legal claims in this regard. First, they argue that gene patents violate the Federal patent statute, which—as interpreted by the courts—says that products of nature and laws of nature are not patentable subject matter. Defenders of gene patents contend they are valid because they apply to genes in their “isolated and purified” state, but the ACLU and Public Patent Foundation argue that “[h]uman genes, even when removed from the body, are still products of nature, and their associations with diseases are laws of nature.”

Second, the lawsuit claims that gene patents violate the Constitution’s patent clause, which gives Congress the authority to “promote the Progress of Science and useful Arts, by securing for limited Times to Authors and Inventors the exclusive Right to their respective Writings and Discoveries.” But awarding patents on human genes fails to promote the progress of science, the lawsuit says; in fact, it “slow[s] scientific advancement, because there is no way to invent around a gene—the gene is the basis for all subsequent research.” However, backers of gene patents highlight their utility, claiming they provide important incentives for socially beneficial discoveries.

Third, the lawsuit makes the novel argument that, because the BRCA patents and most gene patents cover the actual variation among individuals’ genes and the relationship between the genes and biology, they violate the First Amendment. The plaintiffs hold that while a gene test is a patentable invention, a claim to all of a

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gene’s tests, variants and biological roles is not. A gene, argues the lawsuit and many scientists, is both a basic research tool and an idea, and thus patents on them amount to prohibitions on thinking about the genes’ roles. Patents are meant to provide an incentive to build a better mousetrap, but human gene patents, in effect, claim the entire concept of catching mice.

Summarizing the legal and political arguments, ACLU Executive Director Anthony Romero said in a May press statement,

Knowledge about our own bodies and the ability to make decisions about our health care are some of our most personal and fundamental rights. The government should not be granting private entities control over something as personal and basic to who we are as our genes. Moreover, granting patents that limit scientific research, learning and the free flow of information violates the First Amendment. The ACLU/Public Patent Foundation suit is the first with a chance of getting the Supreme Court to consider how the “product of nature” and the “isolated and purified” doctrines should be applied to human gene patents, and the first patent challenge to invoke the First Amendment. It’s also the first challenge supported by a large number of prestigious scientists who explicitly counter the argument that gene patents are needed for scientific progress.

To date, U.S. courts have had far more to say about human gene patents than has Congress or the Executive Branch. The focus has thus been on technical legal issues rather than on social consequences and the broader public welfare. Although granting intellectual property rights on human genes strikes many people as odd if not morally wrong, and certainly as a new development that ought to be debated, the broader concerns and questions have not been much considered even by policymakers or elected officials, and certainly not by the public.

There has been at least one recent exception, however. In 2007, a bipartisan bill crafted by Representatives Xavier Becerra (D-CA) and Dave Weldon (R-FL) proposed to disallow future human gene patents. Their Genomic Research and Accessibility Act was a model of simplicity. Its 180 words would have added a “prohibition on patent of human genetic material” to the U.S. Code. In a statement on his website, Becerra argued in 2007 that “Congress has the constitutional right to proliferate and reward the advancement of invention, but it also has the responsibility to intervene should that advancement be misdirected or incorrect.”

The Becerra-Weldon bill received high-profile support from the late Michael Crichton, the best-selling author of science-based thrillers like Next (2006), whose plot centers on a greedy corporation bent on protecting its gene patents at all costs. A Wall Street Journal review said that Crichton “makes five eminently sensible policy suggestions” about human gene patents that “might chafe some biotech companies, but are essentially pro-market and pro-research.” In a February 2007 New York Times op-ed applauding the bill, Crichton wrote, “Genes aren’t human inventions, they are features of the natural world. You can’t patent snow, eagles or gravity, and you shouldn’t be able to patent genes, either.” The bill died in committee, but Becerra plans to reintroduce it soon in very similar form. Supporters of the bill are careful to make clear that they do not oppose patents in general, and that they strongly support medical research.

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The legal basis for patents derives from interpretations of the Constitution, in which the Federal government’s authority to oversee intellectual property is among its few enumerated powers. By the mid-19th century, the foundation of modern intellectual property law had been set: Patents may be granted on a “process, machine, manufacture, or composition of matter” that is novel, useful and non-obvious (the last characteristic was added by an 1850 court case).

Claims on natural substances and processes have been particularly controversial from the outset. In 1853, the Supreme Court rejected one of Robert Morse’s patent claims to the telegraph, declaring that electromagnetism itself is “a principle of nature” and thus outside the purview of patents. In subsequent cases, American courts walked a fine and sometimes seemingly contradictory line in judging the patentability of natural substances. In 1884, the Supreme Court declared that a synthesized chemical with the same structure as one found in nature cannot be patented. Then in 1912, a Federal circuit court held that “isolated and purified” adrenaline, which is found in nature but only in a more dilute form, can be subjected to patent claims. Soon after World War II, the Supreme Court ruled that a proprietary mixture of bacteria, each kind of which occurs naturally but not collectively, cannot be patented. A case often cited as a turning point in the history of patents on biological entities is Diamond v. Chakrabarty (1980), in which the Supreme Court held in a five-to-four ruling that life forms created in the laboratory are patentable. The “invention” in question in this ruling was a modified bacterium that a patent examiner had originally found to be outside the legal definition of patentable “subject matter” on the grounds that it was a living organism. Others observed that the microbe was merely a mixture of genes found in nature. But the Court majority said that it is a product of manufacture, not of nature, and that “anything under the sun that is made by man” is subject to patent claims. Despite citations of Chakrabarty in many accounts of gene patents, the ruling did not address the patentability of genes. In fact, the Supreme Court in its ruling specifically said:

The laws of nature, physical phenomena, and abstract ideas have been held not patentable. Thus, a new mineral discovered in the earth or a new plant found in the wild is not patentable subject matter. . . . Such discoveries are ‘manifestations of . . . nature, free to all men and reserved exclusively to none.’

Two years later, the USPTO granted the first patent for a human gene sequence to the University of California for the “isolated and purified” form of a gene that encodes the insulin protein. Myriad Genetics filed for its patents on the BRCA genes in 1994 and 1995. After several years of legal skirmishes, it established complete control over them by 1999.

But the gene patent gold rush really began in earnest when the private biotech company Celera, led by publicity-seeking scientist-entrepreneur Craig Venter, initiated a race with the publicly funded Human Genome Project. Celera used newly developed techniques to identify short sections of DNA that can be used to identify genes, though their function may be unknown. Its business model was to patent these DNA fragments quickly, and then to sort out their usefulness later. These patents on DNA fragments alarmed many scientists, who feared that they would interfere with subsequent research. In 2001, the USPTO tightened its regulations to

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exclude some DNA sequences, but it continues to grant patents on human genes and some DNA fragments.

If the United States has pushed the envelope on patenting human genes, its permissive policy has pulled the rest of the world in its direction. The primary international agreement governing intellectual property, the Trade-Related Intellectual Property Rights Agreement (TRIPS) of the World Trade Organization, requires nations to make patents available for inventions that are “new, involve an inventive step, and are capable of industrial application.” This standard is similar to the traditional U.S. approach, although TRIPS permits denials for reasons of public health, or if a patent would be contrary to “public order or morality.”

European Union policies are not far from those of the United States, despite its generally stronger resistance to the “commodification of life.” Unlike the United States but like TRIPS, the European Patent Office (EPO) permits public health and morality exceptions, although in practice they are almost never exercised. Its 1998 Directive on human gene patents also explicitly removes some practices, such as human cloning and genetic modification, from the purview of patent claims.

Myriad’s BRCA gene patents, in particular, have not fared well internationally. After years of challenges, the EPO only recently reached a compromise that partially allows them. Ontario, Canada’s most populous province, is simply ignoring the patent, and conducting its own BRCA tests at publicly funded labs at a far lower cost.

Public concerns about patents on genes and other biological products are often couched as opposition to “owning life.” The phrase bespeaks disquiet about the very idea of treating human tissues and genes as private property to be exploited for profit rather than managed in the public interest. Various international bodies have declared the human genome to be part of a “commons.” The Universal Declaration on the Human Genome and Human Rights, ratified by the United Nations General Assembly in 1998, states that the “human genome . . . is the heritage of humanity” and “in its natural state shall not give rise to financial gains.” In 1999, the Parliamentary Assembly of the Council of Europe, a 47-member intergovernmental human rights body, declared “that neither plant, animal nor human derived genes, cells, tissue or organs can be considered as inventions nor be subject to monopolies granted by patents.” The World Medical Association, an umbrella for 84 national medical associations, states that “human genes must be seen as mankind’s common heritage.” Defenders of gene patents scoff at such notions. They point out (correctly, in a narrow sense) that the genes residing in your body are not “owned” any more than your computer is owned by those who hold the patents for its components. They argue that without patent protection, biotech companies would be unable to fund the research and development of new drugs and treatments—processes that may be privately profitable but also publicly beneficial. They claim, in short, that without patents, there will be no cures. A response from the American Enterprise Institute to the gene patent challenge by the ACLU and Public Patent Foundation is typical. AEI resident scholar John Chalfee argued that high prices are the expectable and legitimate consequence of patents, and that gene patents haven’t really hindered research. He concludes that “gene patents are turning out to work more or less the

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way patents are supposed to work and have been working for a couple of centuries and more. The research process, and ultimately patients, are the beneficiaries.”

That many financial backers of the biotechnology industry believe patents are necessary to protect their investments was starkly illustrated by an episode in the competition between Celera and the Human Genome Project. In March 2000, in anticipation of an announcement that a “rough draft” of the genome had been completed, President Bill Clinton and British Prime Minister Tony Blair issued a 200-word joint statement, apparently aimed at Celera, applauding the Human Genome Project’s decision to “release raw fundamental information about the human DNA sequence and its variants rapidly into the public domain” and called on “other scientists around the world to adopt this policy.” Though the statement explicitly supported “intellectual property protection for gene-based inventions”, the stock prices of Celera, as well as Incyte and Human Genome Sciences, immediately plunged. The White House and National Institutes of Health quickly backpedaled.

Public interest opposition to “patents on life” has been stronger in other countries, but there have been U.S. challenges as well. In the 1980 Chakrabarty case, a public interest group led by Jeremy Rifkin filed an amicus curiae brief in support of the USPTO’s original rejection of the patent claim on the genetically modified oil-eating bacterium, on the grounds that it was a living organism. It raised social and moral concerns about “manufactured life” and contended that Congress, not the courts, was the appropriate venue for consideration of how this fundamentally new technology should be governed. Writing for the four-justice minority, William Brennan agreed that “it is the role of Congress, not this court, to broaden or narrow the reach of patent laws”, and said that Congressional guidance is crucial because “the composition sought to be patented uniquely implicated matters of public concern.”

In 1994, more than thirty organizations representing indigenous peoples formally announced their opposition to patenting genes and biological tissues taken from members of their groups. In 1995, a coalition of some 180 religious leaders issued a “Joint Appeal against Human and Animal Patenting.” The same year, Congress considered but rejected a bill that would have disallowed many kinds of gene patents. In 1996, Rifkin’s Foundation on Economic Trends put together a coalition of more than 400 women’s organizations in more than forty nations to challenge Myriad’s breast cancer gene patents. In 2000, the Council for Responsible Genetics issued its ten-point “Genetic Bill of Rights”, one of which reads, “All people have the right to a world in which living organisms cannot be patented, including human beings, animals, plants, microorganisms and all their parts.”

Less frequently, debates about human gene patents have reached into the Federal legislative and executive branches. In 2002, a bipartisan bill was introduced into Congress to institute a research and diagnostic testing exemption for gene patents, of the sort provided by many other countries’ intellectual property laws. At the same time, the Federal Trade Commission and Department of Justice were studying whether patents were stifling rather than encouraging innovation. A government panel heard from the biotech company Affymetrix, one of the dissenters from most of the industry’s support for human gene patents. The company’s general

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counsel, Barbara Caulfield, said bluntly, “There should be no patenting of gene sequences, period. They were invented by nature.”

A number of non-commercial scientific organizations are critical of at least certain aspects of U.S. patent policy. The American Society of Human Genetics and the international Human Genome Organisation, while generally supportive of gene patents, oppose claims to sequences whose functions are unknown. Similarly, the American Association of Medical Colleges argues that patents with medical uses should be widely licensed without excessive royalties. In contrast, the Association for Molecular Pathology, the American College of Medical Genetics, the American Society for Clinical Pathology and the College of American Pathologists are plaintiffs in the ACLU’s and Public Patent Foundation’s challenge to Myriad’s claims. As this sketch suggests, the legal issues are enormously complex, and various actors see their interests in many different ways.

Human gene patents raise three kinds of basic questions, and the fate of the current challenges to them—both the lawsuit against the holders of the patents for the breast cancer genes and the Congressional bill to halt human gene patents—will be determined by how they are answered. First, are human gene patents legal? The present policy evolved in incremental steps at the USPTO and in court rulings. Does the USPTO actually have the legal authority to grant these patents, or has it exceeded its authority? Although the Supreme Court has heard related cases, neither it nor Congress has ever directly addressed this question.

Second, what are the practical consequences of patents on human genes? Do they effectively balance incentives for innovation with the promotion of science? As scientists increasingly learn that segments of DNA perform multiple functions, they are concluding that the potential for complicated, overlapping intellectual property claims is significant. Myriad has become a prime target of gene patent critics for its aggressive patent enforcement, but the general problem of “patent thickets” that interfere with research and development is growing.

Third, what are the social and ethical implications of human gene patents? While the public as well as policymakers strongly support biomedical research, the extension of property claims deep into areas formerly considered outside the commercial realm has stirred great unease across the political spectrum. Patents on human genes, along with other novel biotechnology practices, introduce profound questions about our relationships to each other and the natural world. These matters overflow the boundaries of evaluative criteria based on legal precedents and economic expediency.

They go to the very core of who we think we are and how we view each other. Too often, discussions of biotech practices and products gloss over these deeper concerns. The tendency is to narrow the conversation to technical issues (for example, the legal status of patents on life, the environmental impacts of synthetic biology experiments, the health risks of efforts to clone human beings) and to procedural considerations (for example, informed consent, disclosing conflicts of interest, bio-containment precautions). All of these are important. But in grappling with emerging biotechnological innovations, public discussion must also tackle the goals and purposes of our techno-scientific enterprises; their consequences for social justice, human rights and democracy; and the ways they shape us as

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individuals, as members of communities, and as upholders of a shared humanity. Today’s debate over patents on human genes has the potential to set social, cultural and political precedents, as well as legal ones, for addressing some of the most profound questions we currently confront. Conclusion

Firstly, human genes are the products of nature, even when they are purified from body. At the same time, the human genes’ associations with diseases are also the laws of nature, nobody can prevent others from studying about them. Secondly, human gene patented will not promote the development of science. Because the gene is the basis for all the research, patent of genes will destroy this basis. Third, all the researches need use the genes as the basic tool and study about their functions. If the genes are patented, most of the research will be controlled by small amount of people or companies, which will hinder the scientific research.

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SUPPLEMENTARY MATERIALS ON US PATENT LAW:

Source: US Patent Office Website. http://www.uspto.gov/web/offices/pac/mpep/documents/appxl_35_U_S_C_101.htm

Accessed: 19 April 2010 35 U.S.C. 101 Inventions patentable.

Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.

35 U.S.C. 102 Conditions for patentability; novelty and loss of right to patent.

A person shall be entitled to a patent unless -

(a) the invention was known or used by others in this country, or patented or described in a printed publication in this or a foreign country, before the invention thereof by the applicant for patent, or

(b) the invention was patented or described in a printed publication in this or a foreign country or in public use or on sale in this country, more than one year prior to the date of the application for patent in the United States, or

(c) he has abandoned the invention, or

(d) the invention was first patented or caused to be patented, or was the subject of an inventor's certificate, by the applicant or his legal representatives or assigns in a foreign country prior to the date of the application for patent in this country on an application for patent or inventor's certificate filed more than twelve months before the filing of the application in the United States, or

(e) the invention was described in - (1) an application for patent, published under section 122(b), by another filed in the United States before the invention by the applicant for patent or (2) a patent granted on an application for patent by another filed in the United States before the invention by the applicant for patent, except that an international application filed under the treaty defined in section 351(a) shall have the effects for the purposes of this subsection of an application filed in the United States only if the international application designated the United States and was published under Article 21(2) of such treaty in the English language; or

(f) he did not himself invent the subject matter sought to be patented, or

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(g)(1) during the course of an interference conducted under section 135 or section 291, another inventor involved therein establishes, to the extent permitted in section 104, that before such person's invention thereof the invention was made by such other inventor and not abandoned, suppressed, or concealed, or (2) before such person's invention thereof, the invention was made in this country by another inventor who had not abandoned, suppressed, or concealed it. In determining priority of invention under this subsection, there shall be considered not only the respective dates of conception and reduction to practice of the invention, but also the reasonable diligence of one who was first to conceive and last to reduce to practice, from a time prior to conception by the other.

(Amended July 28, 1972, Public Law 92-358, sec. 2, 86 Stat. 501; Nov. 14, 1975, Public Law 94-131, sec. 5, 89 Stat. 691.)

(Subsection (e) amended Nov. 29, 1999, Public Law 106-113, sec. 1000(a)(9), 113 Stat. 1501A-565 (S. 1948 sec. 4505).)

(Subsection (g) amended Nov. 29, 1999, Public Law 106-113, sec. 1000(a)(9), 113 Stat. 1501A-590 (S. 1948 sec. 4806).)

(Subsection (e) amended Nov. 2, 2002, Public Law 107-273, sec. 13205, 116 Stat. 1903.)

35 U.S.C. 103 Conditions for patentability; non-obvious subject matter.

(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.

(b)

(1) Notwithstanding subsection (a), and upon timely election by the applicant for patent to proceed under this subsection, a biotechnological process using or resulting in a composition of matter that is novel under section 102 and nonobvious under subsection (a) of this section shall be considered nonobvious if-

(A) claims to the process and the composition of matter are contained in either the same application for patent or in separate applications having the same effective filing date; and

(B) the composition of matter, and the process at the time it was invented, were owned by the same person or subject to an obligation of assignment to the same person.

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(2) A patent issued on a process under paragraph (1)-

(A) shall also contain the claims to the composition of matter used in or made by that process, or

(B) shall, if such composition of matter is claimed in another patent, be set to expire on the same date as such other patent, notwithstanding section 154.

(3) For purposes of paragraph (1), the term "biotechnological process" means-

(A) a process of genetically altering or otherwise inducing a single- or multi-celled organism to-

(i) express an exogenous nucleotide sequence,

(ii) inhibit, eliminate, augment, or alter expression of an endogenous nucleotide sequence, or

(iii) express a specific physiological characteristic not naturally associated with said organism;

(B) cell fusion procedures yielding a cell line that expresses a specific protein, such as a monoclonal antibody; and

(C) a method of using a product produced by a process defined by subparagraph (A) or (B), or a combination of subparagraphs (A) and (B).

(c)

(1) Subject matter developed by another person, which qualifies as prior art only under one or more of subsections (e), (f), and (g) of section 102 of this title, shall not preclude patentability under this section where the subject matter and the claimed invention were, at the time the claimed invention was made, owned by the same person or subject to an obligation of assignment to the same person.

(2) For purposes of this subsection, subject matter developed by another person and a claimed invention shall be deemed to have been owned by the same person or subject to an obligation of assignment to the same person if -

(A) the claimed invention was made by or on behalf of parties to a joint research agreement that was in effect on or before the date the claimed invention was made;

(B) the claimed invention was made as a result of activities undertaken within the scope of the joint research agreement; and

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(C) the application for patent for the claimed invention discloses or is amended to disclose the names of the parties to the joint research agreement.

(3) For purposes of paragraph (2), the term "joint research agreement" means a written contract, grant, or cooperative agreement entered into by two or more persons or entities for the performance of experimental, developmental, or research work in the field of the claimed invention.

(Amended Nov. 8, 1984, Public Law 98-622, sec. 103, 98 Stat. 3384; Nov. 1, 1995, Public Law 104-41, sec.1, 109 Stat. 3511.)

(Subsection (c) amended Nov. 29, 1999, Public Law 106-113, sec. 1000(a)(9), 113 Stat. 1501A-591 (S. 1948 sec. 4807).)

(Subsection (c) amended Dec. 10, 2004, Public Law 108-453 , sec. 2, 118 Stat. 3596.)

35 U.S.C. 104 Invention made abroad.

(a) IN GENERAL.-

(1) PROCEEDINGS.-In proceedings in the Patent and Trademark Office, in the courts, and before any other competent authority, an applicant for a patent, or a patentee, may not establish a date of invention by reference to knowledge or use thereof, or other activity with respect thereto, in a foreign country other than a NAFTA country or a WTO member country, except as provided in sections 119 and 365 of this title.

(2) RIGHTS.-If an invention was made by a person, civil or military-

(A) while domiciled in the United States, and serving in any other country in connection with operations by or on behalf of the United States,

(B) while domiciled in a NAFTA country and serving in another country in connection with operations by or on behalf of that NAFTA country, or

(C) while domiciled in a WTO member country and serving in another country in connection with operations by or on behalf of that WTO member country, that person shall be entitled to the same rights of priority in the United States with respect to such invention as if such invention had been made in the United States, that NAFTA country, or that WTO member country, as the case may be.

(3) USE OF INFORMATION.-To the extent that any information in a NAFTA country or a WTO member country concerning knowledge, use, or other activity relevant to proving or disproving a date of invention has not been made available for use in a proceeding in the Patent and Trademark Office, a court, or any other competent authority to the same extent as such information could be made available in the United States, the Director, court, or such other authority shall draw appropriate

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inferences, or take other action permitted by statute, rule, or regulation, in favor of the party that requested the information in the proceeding.

(b) DEFINITIONS.-As used in this section-

(1) The term "NAFTA country" has the meaning given that term in section 2(4) of the North American Free Trade Agreement Implementation Act; and

(2) The term "WTO member country" has the meaning given that term in section 2(10) of the Uruguay Round Agreements Act.

(Amended Jan. 2, 1975, Public Law 93-596, sec. 1, 88 Stat. 1949; Nov. 14, 1975, Public Law 94-131, sec. 6, 89 Stat. 691; Nov. 8, 1984, Public Law 98-622, sec. 403(a), 98 Stat. 3392; Dec. 8, 1993, Public Law 103-182, sec. 331, 107 Stat. 2113; Dec. 8, 1994, Public Law 103-465, sec. 531(a), 108 Stat. 4982; Nov. 29, 1999, Public Law 106-113, sec. 1000(a)(9), 113 Stat. 1501A-582 (S. 1948 sec. 4732(a)(10)(A)).)