Association For Molecular Pathology et al v. United States Patent and Trademark Office et al

Filing 63

RULE 56.1 STATEMENT. Document filed by American Society For Clinical Pathology, College of American Pathologists, Association For Molecular Pathology, Haig Kazazian, Arupa Ganguly, Wendy Chung, Harry Ostrer, David Ledbetter, Stephen Warren, Ellen Matloff, Elsa Reich, Breast Cancer Action, Boston Women's Health Book Collective, American College of Medical Genetics, Lisbeth Ceriani, Runi Limary, Genae Girard, Patrice Fortune, Vicky Thomason, Kathleen Raker. (Hansen, Christopher)

Association For Molecular Pathology et al v. United States Patent and Trademark Office et al Doc. 63 UNITED STATES DISTRICT COURT SOUTHERN DISTRICT OF NEW YORK --------------------------------------------------------------------------x ASSOCIATION FOR MOLECULAR PATHOLOGY; AMERICAN COLLEGE OF MEDICAL GENETICS; AMERICAN SOCIETY FOR CLINICAL PATHOLOGY; COLLEGE OF AMERICAN PATHOLOGISTS; HAIG KAZAZIAN, MD; ARUPA GANGULY, PhD; WENDY CHUNG, MD, PhD; HARRY OSTRER, MD; DAVID LEDBETTER, PhD; STEPHEN WARREN, PhD; ELLEN MATLOFF, M.S.; ELSA REICH, M.S.; BREAST CANCER ACTION; BOSTON WOMEN'S HEALTH BOOK COLLECTIVE; LISBETH CERIANI; RUNI LIMARY; GENAE GIRARD; PATRICE FORTUNE; VICKY THOMASON; KATHLEEN RAKER, Plaintiffs, 09 Civ. 4515 (RWS) ECF Case v. UNITED STATES PATENT AND TRADEMARK OFFICE; MYRIAD GENETICS; LORRIS BETZ, ROGER BOYER, JACK BRITTAIN, ARNOLD B. COMBE, RAYMOND GESTELAND, JAMES U. JENSEN, JOHN KENDALL MORRIS, THOMAS PARKS, DAVID W. PERSHING, and MICHAEL K. YOUNG, in their official capacity as Directors of the University of Utah Research Foundation, Defendants. --------------------------------------------------------------------------x Pursuant to Local Rule 56.1, plaintiffs submit the following statement of material facts. PLAINTIFFS 1. Plaintiff ASSOCIATION FOR MOLECULAR PATHOLOGY (AMP) is a notPLAINTIFFS' RULE 56.1 STATEMENT OF MATERIAL FACTS for-profit scientific society dedicated to the advancement, practice, and science of clinical molecular laboratory medicine and translational research based on the applications of genomics and proteomics. AMP members participate in basic and translational research aimed at broadening the understanding of gene/protein structure and function, disease processes, and Dockets.Justia.com molecular diagnostics, and provide clinical medical services for patients, including diagnosis of breast cancer. AMP believes that a single gene "is a product of nature and should not be patentable . . . Gene patents can serve as a disincentive to innovation in molecular testing, because they deny access to a vital baseline of genomic information that cannot be `invented around.'" D. Sobel 2, 4-5.1 2. Plaintiff AMERICAN COLLEGE OF MEDICAL GENETICS (ACMG) is a private, non-profit voluntary organization of clinical and laboratory geneticists. The Fellows of the ACMG are doctoral level medical geneticists and other physicians involved in the practice of medical genetics. With more than 1300 members, the ACMG's mission is to improve health through the practice of Medical Genetics. In order to fulfill this mission, the ACMG strives to 1) define and promote excellence in medical genetics practice and the integration of translational research into practice; 2) promote and provide medical genetics education; 3) increase access to medical genetics services and integrate genetics into patient care; and 4) advocate for and represent providers of medical genetics services and their patients. It is ACMG's position that "Genes and their mutations are naturally occurring substances that should not be patented." D. Watson 2, 4-5. 3. Founded in 1922, the plaintiff AMERICAN SOCIETY FOR CLINICAL PATHOLOGY (ASCP) is the largest and oldest organization representing the medical specialty of pathology and laboratory medicine. The ASCP has 130,000 members working as pathologists and laboratory professionals. ASCP members design and interpret the tests that detect disease, predict outcome, and determine the appropriate therapy for the patient. The ASCP is recognized for its excellence in continuing professional education, certification of laboratory professionals, 1 D. ____ identifies a declaration filed in support of the motion for summary judgment. Thus, D. Sobel is the declaration of Dr. Mark Sobel. 2 and advocacy--championing causes at the state and federal levels. ASCP is a not-for-profit entity organized for scientific and educational purposes and dedicated to patient safety, public health, and the practice of pathology and laboratory medicine. ASCP believes "the practice of gene patenting harms patients, impedes advances in medicine, and limits those in the practice of pathology and laboratory medicine from doing what they are educated to do provide high quality health care and engage in research that will enhance the practice of medicine and patient care." D. Ball 2, 5. 4. Plaintiff COLLEGE OF AMERICAN PATHOLOGISTS (CAP) is a national medical society representing more than 17,000 pathologists who practice anatomic pathology and laboratory medicine in laboratories worldwide. The College's Commission on Laboratory Accreditation is responsible for accrediting more than 6,000 laboratories domestically and abroad, and approximately 23,000 laboratories are enrolled in CAP's proficiency testing programs. It is the world's largest association composed exclusively of board-certified pathologists and pathologists in training worldwide and is widely considered the leader in laboratory quality assurance. CAP is an advocate for high-quality and cost-effective medical care. CAP "believes that genes and their variants (to include mutations) are naturally occurring substances and should not be patented." D. Scott 2, 4-5. 5. Plaintiff HAIG KAZAZIAN, MD, is the Seymour Gray Professor of Molecular Medicine in Genetics in the Department of Genetics at the University of Pennsylvania School of Medicine. He is a human genetics researcher and the previous chair of the Department. Dr. Kazazian and Arupa Ganguly, another plaintiff, designed tests to screen the BRCA1 and BRCA2 genes in their lab and provided screening to approximately 500 women per year starting in 1996 until they were forced to stop offering testing by Myriad. D. Kazazian 1-5. 3 6. Plaintiff ARUPA GANGULY, PhD, is an Associate Professor in the Department of Genetics at the Hospital of the University of Pennsylvania. Dr. Ganguly's work previously included BRCA1/2 screening for both research and clinical purposes. She was compelled to stop BRCA screening after Myriad accused her lab of violating the patents. D. Ganguly 1, 3-4. 7. Plaintiff WENDY CHUNG, MD, PhD, is an Associate Professor of Pediatrics at Columbia University. Dr. Chung is a human geneticist whose current research includes research on the BRCA1 and BRCA2 genes. Because of the patents, Dr. Chung currently cannot tell research subjects in her studies the results of their BRCA1/2 tests and cannot offer clinical BRCA testing services. D. Chung 1-9, 11-13, 16. 8. Plaintiff HARRY OSTRER, MD, is a Professor of Pediatrics, Pathology and Medicine and Director of the Human Genetics Program in the Department of Pediatrics at New York University School of Medicine. Dr. Ostrer's work has focused on understanding the genetic basis of development and disease, including disorders of sexual differentiation and genetic susceptibility to breast and prostate cancer and malignant melanoma. Dr. Ostrer is actively engaged in identifying genes that convey risk of breast cancer and that may mitigate the effects of mutations in the BRCA1 and BRCA2 genes. Dr. Ostrer is also the Director of the Molecular Genetics Laboratory of NYU Medical Center, one of the largest academic genetic testing laboratories in the United States. Because of the patents, Dr. Ostrer currently cannot tell research subjects in his studies the results of their BRCA1/2 tests and cannot offer clinical BRCA testing services. D. Ostrer 1-4, 8, 10, 12. 9. Plaintiff DAVID LEDBETTER, PhD, is a Professor of Human Genetics and Director of the Division of Medical Genetics at the Emory University School of Medicine. Dr. Ledbetter is a genetic researcher. Research in his laboratory focuses on the molecular 4 characterization of human developmental disorders. Dr. Ledbetter directs the Emory Genetics Laboratory which provides testing services for individuals with or at risk for genetic diseases. Because of the patents, Dr. Ledbetter cannot offer comprehensive BRCA genetic testing to patients. D. Ledbetter 1-8, 16. 10. Plaintiff STEPHEN T. WARREN, PhD, is the William Patterson Timmie Professor of Human Genetics, Chairman of the Department of Human Genetics, and Professor of Biochemistry and Professor of Pediatrics at Emory University. He is a past President of the American Society of Human Genetics. He personally supervises genetic research at Emory. He is also responsible for the laboratories at the Emory Genetics Laboratory. These laboratories would offer BRCA genetic testing but for the patents. D. Ledbetter 1, 16. 11. Plaintiff ELLEN MATLOFF, M.S., is Director of the Yale Cancer Genetic Counseling Program. Ms. Matloff advises women on the desirability of obtaining an analysis of their genes to determine if the women have the genetic mutations that correlate with an increased risk of breast and/or ovarian cancer. If she determines that such an analysis is warranted and the individual woman concurs, Ms. Matloff arranges for the analysis and then advises the woman of the significance of the results. Ms. Matloff would like to have the option to send patient samples to laboratories other than Myriad Genetics for BRCA1/2 sequencing. D. Matloff 1-4, 11. 12. Plaintiff ELSA W. REICH, M.S., is a Professor in the Department of Pediatrics at New York University. She is a genetic counselor. She helps women decide whether to be tested for mutations in the BRCA1 and BRCA2 genes. If they need testing, she sends samples to defendant Myriad and explains the results for the women. Ms. Reich would like to have the option to send patient samples to laboratories other than Myriad Genetics for BRCA1/2 sequencing. D. Reich 1-3, 8. 5 13. Plaintiff BREAST CANCER ACTION (BCA) is a national organization of approximately 30,000 members based in San Francisco, California. Breast Cancer Action is dedicated to carrying the voices of people affected by breast cancer in order to inspire and compel the changes necessary to end the breast cancer epidemic. Its members include breast cancer survivors, family members of people diagnosed with breast cancer and other people affected by or concerned about breast cancer. BCA advocates for policy changes directed at achieving prevention, finding better treatments, and reducing the incidence of breast cancer; provides information about breast cancer to anyone who needs it via newsletters, web sites, email and a toll-free number; and organizes people to get involved in advocacy to advance its policy goals. BCA believes that the BRCA gene patents interfere with people's ability to participate fully in decisions relating to breast cancer treatment and to gain access to information about breast cancer and quality health care. D. Brenner 1-4. 14. Plaintiff BOSTON WOMEN'S HEALTH BOOK COLLECTIVE (BWHBC), doing business as Our Bodies Ourselves (OBOS), is a nonprofit, public interest women's health education, advocacy, and consulting organization. OBOS provides clear, accurate information about health, sexuality and reproduction from a feminist and consumer perspective. OBOS vigorously advocates for women's health by challenging the institutions and systems that block women from full control over their bodies and devalue women's lives. OBOS's long-standing commitment to serve only in the public interest and its bridge-building capacity are its hallmarks. In addition, OBOS staff provide information to members of the public about genetic analysis. OBOS believes that the BRCA gene patents are a barrier to a woman's ability to know about her body and make informed health decisions. D. Norsigian 1-4, 7. 6 15. Plaintiff LISBETH CERIANI is a 43-year-old single mother who was diagnosed with cancer in both breasts in May 2008. Ms. Ceriani is insured through MassHealth, a Medicaid insurance program for low-income people. Her oncologist and genetic counselor recommended that she obtain BRCA1 and BRCA2 genetic testing, because she may need to consider further surgery in order to reduce her risk of ovarian cancer. However, Myriad will not accept the MassHealth coverage. Ms. Ceriani is unable to pay the full cost out-of-pocket. D. Ceriani 1-5. 16. Plaintiff RUNI LIMARY is a 32-year-old Asian-American woman who was diagnosed with aggressive breast cancer in 2005. Ms. Limary obtained BRCA testing through Myriad and received the following result: "genetic variant of uncertain significance." D. Limary 1-5. 17. Plaintiff GENAE GIRARD is a 39-year-old woman who was diagnosed with breast cancer in 2006. Shortly after her diagnosis, she obtained BRCA1/BRCA2 genetic testing from Myriad and tested positive for a deleterious mutation on the BRCA2 gene. She sought a second opinion of that test result but learned that Myriad is the only laboratory in the country that can provide full BRCA sequencing. D. Girard 1-7. 18. Plaintiff PATRICE FORTUNE is a 48-year-old woman who was diagnosed with breast cancer in February 2009. Ms. Fortune is insured through Medi-Cal. Her oncologist and genetic counselor recommended that she obtain BRCA1/BRCA2 genetic testing, including the supplemental testing that is offered by Myriad separate from its standard test, but told her that Myriad would not accept her insurance. Ms. Fortune is unable to pay the full cost out-of-pocket. D. Fortune 1-5. 7 19. Plaintiff VICKY THOMASON is a 52-year-old woman who was diagnosed with ovarian cancer in 2006. She obtained BRCA1/BRCA2 genetic testing from Myriad in 2007 and was found to be negative for mutations covered by that test. Her genetic counselor advised her about additional BRCA genetic testing offered by Myriad that looks for other large genetic rearrangements that are not included in Myriad's standard full sequencing test, but informed her that her insurance would not cover the full cost of that test. Ms. Thomason is unable to afford the extra cost. D. Thomason 1-8. 20. Plaintiff KATHLEEN RAKER is a 41-year-old woman whose mother and maternal grandmother died from breast cancer. She obtained BRCA1/BRCA2 genetic testing from Myriad in 2007 and was found to be negative for mutations covered by that test. Her genetic counselor advised her about additional BRCA genetic testing offered by Myriad that looks for other large genetic rearrangements that are not included in Myriad's standard full sequencing test, but informed her that it was unclear whether her insurance would not cover the full cost of that test. Ms. Raker is unable to afford the extra cost. D. Raker 1-9. EXPERT DECLARANTS 21. Dr. John Sulston, Nobel Prize winner for Physiology or Medicine and Chair of the Institute for Science, Ethics, and Innovation at the University of Manchester (UK), is qualified to express expert opinions in the area of human genetics. D. Sulston 1-9. 22. Dr. Wayne Grody, Professor in the Department of Pathology and Laboratory Medicine, Pediatrics, and Human Genetics at the UCLA School of Medicine, is qualified to express expert opinions in the area of human genetics. D. Grody 1-3. 8 23. Dr. Debra Leonard, Professor of Pathology and Laboratory Medicine at Weill Cornell Medical College and New York-Presbyterian Hospital, is qualified to express expert opinions in the area of human genetics. D. Leonard 1-10. 24. Dr. Christopher Mason, Post-doctoral Associate in the Program on Neurogenetics at Yale University, is qualified to express expert opinions in the area of human genetics. D. Mason 1-3. 25. Dr. Susan Love, Clinical Professor of Surgery at the University of California at Los Angeles and President of the Dr. Susan Love Research Foundation, is qualified to express expert opinions in the area of breast cancer treatment and research. D. Love 1-7. 26. Dr. Elizabeth Swisher, Associate Professor of Obstetrics and Gynecology at the University of Washington School of Medicine, is qualified to express expert opinions in the area of human genetics. D. Swisher 1-9. 27. Dr. Shobita Parthasarathy, Assistant Professor of Public Policy at the University of Michigan School of Public Policy, is qualified to express expert opinions in the area of the history of human genetic testing and research. D. Parthasarathy 1-7. 28. Dr. Myles Jackson, the Dibner Family Professor of the History and Philosophy of Science and Technology at the Polytechnic Institute of New York University, reviewed 12 court cases involving patents that were challenged, including 9 Supreme Court cases to compare the scientific principles and products either granted or denied patents. Dr. Jackson is qualified to express expert opinions in the area of science and patents. D. Jackson 1-6. 29. Dr. Mildred Cho, Associate Director of the Stanford Center for Biomedical Ethics, is qualified to express expert opinions on the need or lack thereof for gene patents to spur 9 research into genes and the effect of such patents on research and clinical practice. D. Cho 18. 30. Dr. Madhuri Hegde, Senior Laboratory Director at the Emory Genetics Laboratory, is qualified to express expert opinions in the area of human genetics. D. Hegde 15. 31. Dr. Roger Hubbard, President and Chief Executive Officer of Molecular Pathology Laboratory Network, Inc., is qualified to express expert opinions in the area of human genetics. D. Hubbard 1-6. 32. Dr. Jeffrey Kant, Director of the Division of Molecular Diagnostics at the University of Pittsburgh Medical Center, is qualified to express expert opinions in the area of human genetics. D. Kant 1-3. 33. Dr. Haig Kazazian is qualified to express expert opinions in the area of human genetics. D. Kazazian 1-3. 34. Dr. Arupa Ganguly is qualified to express expert opinions in the area of human genetics. D. Ganguly 1-3. 35. Dr. Wendy Chung is qualified to express expert opinions in the area of human genetics. D. Chung 1-7. 36. Dr. Harry Ostrer is qualified to express expert opinions in the area of human genetics. D. Ostrer 1-3. 37. Dr. David Ledbetter is qualified to express expert opinions in the area of human genetics. D. Ledbetter 1-6. 38. Ms. Ellen Matloff is qualified to express expert opinions in the area of human genetics. D. Matloff 1-4. 10 39. Ms. Elsa Reich is qualified to express expert opinions in the area of human genetics. D. Reich 1-2. GENES 40. Genes and human genetic sequences are not inventions of humans. They are naturally occurring and are products of nature. D. Sulston 10; D. Ostrer 14; D. Chung 25; D. Mason 33; D. Ledbetter 27; D. Leonard 15. 41. Genes are the basic units of heredity in all living organisms. A gene is a segment of DNA, the molecule that makes life possible. DNA encodes the instructions for the development and functioning of each of our cells. D. Sulston 11. 42. Each human gene has its place on one of the twenty-four chromosomes (numbered 1-22, plus the X and Y sex chromosomes), which together constitute the whole genome. D. Sulston 15. 43. Scientists have long recognized the role of genes in heredity. But it wasn't until 1953 the year that Watson and Crick identified the double-helix structure of DNA that the scientific community came to understand how DNA plays its role. This central discovery for modern biology made it immediately apparent that the structure embodies a linear digital code. This code nucleic acid sequence gets copied more or less faithfully from one generation to the next. D. Sulston 13; D. Mason 8-10, 13. 44. The genetic code is similar to the English alphabet, except that it consists of four letters (A, T, C, and G) rather than 26 (A through Z). The letters of the genetic alphabet correspond to 4 chemical bases (adenine (A), thymine (T), cytosine (C) and guanine (G)). Each gene is typically thousands of bases long, and its sequence of As, Ts, Cs and Gs usually encodes a protein. The code is a set of three-letter words for example TTT, CAG each of which 11 corresponds to one of the twenty amino acids that are the building blocks of proteins. D. Sulston 14-15. 45. When the body creates proteins, it relies on the processes of transcription and translation. During transcription, the DNA unwinds itself inside the cell and a temporary copy is created called a messenger RNA (mRNA). This mRNA contains sections that are unnecessary for the creation of proteins. These regions, known as introns, are removed by the body as a natural process because they will not be necessary for creation of a protein. The regions that remain are called exons and are necessary for creation of a protein. Translation is the naturallyoccurring process of converting the processed mRNA into a protein. The tri-nucleotide segments of mRNA (codons) are converted into amino acids, which create the poly-peptide (protein). In other words, the DNA represented by three letters creates a single amino acid. The amino acids, when linked together, create a protein and the protein does the work of the body. D. Mason 11-12. 46. The genome is contained within almost every cell of the body. It defines obvious traits such as skin tone, eye color, and sex, but also directs the manifestation of very complex traits such as Alzheimer's disease. There are approximately 25,000 genes that make up the human genome. D. Mason 4-5; see D. Sulston 10-11. 47. A genetic sequence is the sequence of letters of a specified section of the human genome. D. Sulston 16; D. Mason 13; D. Chung 10. 48. A genetic sequence is biological information. Like strings of alphabetic text, the genetic sequences are the same regardless of the medium. Whether the data reside in the DNA of an organism, a computer, or as letters on a printed page, the information is the same. The 12 physical form in which they occur is unimportant; what matters is the informational content. D. Sulston 16. 49. The information contained in the genetic sequence is a product of nature. The informational content of a human genetic sequence is fixed. While many inventive steps may have been necessary to allow scientists to extract and read a genetic sequence, the ordering of the 4 letters is determined by nature. D. Sulston 17. 50. Genes are so basic to science that any restriction that prevents scientists from looking at the genes themselves or examining the effects of the genes is fundamentally inconsistent with the advancement of human knowledge. D. Sulston 28, 37; D. Ostrer 14; D. Chung 25; D. Swisher 21; D. Ledbetter 27; D. Love 19. 51. Except for identical twins, no two humans are genetically the same. Variation in the human genome is very common, and each person is estimated to be 99.5% similar, or to have one to five differences every 1000 base pairs (bp). D. Mason 14; D. Sulston 12. 52. Small scale variation can occur, manifested as slight sequence differences between the same genes in different individuals. Thus, for example, a sequence of a gene represented by ...GACTCG... might contain a variation that omits the first C (GATCG) or that adds an extra C at that point (GACCTCG) or that reverses the order of two of the letters (CCATCG). D. Mason 16. 53. Large scale variation can also occur in the genome, such as the addition or deletion of substantial chromosomal regions. Thus, a particular gene may omit several hundred letters at one point or may add several hundred letters where they do not normally exist. Structural variants also can occur, so that up to millions of nucleotides can be missing or 13 duplicated. These extra copies or missing copies of the genome that are larger than 1000 bp are called copy number variants. D. Mason 15, 18. 54. Some variants appear to have little or no effect on the body's processes. There are also variants whose significance is currently unknown ("variants of uncertain significance"). Other variants that interfere with a body's processes, including those that appear to correlate with an increased risk of particular diseases, are called mutations. Mutations can be in the form of the insertion or deletion of a single letter, or rearrangements, deletions or repeated segments of groups of letters. D. Mason 19; D. Sulston 18. 55. Genetic sequencing is the process by which one "reads", or determines the ordering of the 4 letters (A, T, C, and G) within a specified part of the genome. In order to sequence, or read a gene, one has to remove it from the cell of an organism and place it in a form so that it can be replicated outside of the body. Most commonly, scientists use a technique called PCR to replicate small segments of the gene many times over. Amplifying these segments allows scientists to read out the genetic code. D. Sulston 20, 25; D. Chung 10. 56. Sequencing of a gene can be done by several processes that are well-known and understood by scientists. Anyone skilled in molecular biology has the knowledge and methods to sequence and examine any part of the human genome. D. Chung 10; D. Mason 24-30; D. Swisher 23-24; D. Kant 5; D. Sulston 20-21, 23; D. Ledbetter 21-22; D. Leonard 18. 57. Scientists and clinicians sequence and analyze genes literally every day. D. Chung 10-11; D. Hegde 6-7; D. Hubbard 3-6; D. Mason 22, 31; D. Sulston 21-22; D. Ledbetter 9-10, 22. 58. The process of sequencing is designed simply to illuminate the information that nature has dictated in that person's genome. In that respect, sequencing is essentially no 14 different than looking at something through a microscope. It takes something created by nature but too small to be seen and makes it visible. D. Mason 23; D. Sulston 18. 59. The process of sequencing a gene does not change the informational content of that gene. The resultant sequence is informationally and functionally identical to the sequence found inside the body. D. Sulston 27; D. Chung 10; D. Mason 32-33. 60. The alterations or mutations in the gene that scientists are able to see after sequencing the gene were made by nature, not by the process of sequencing or by scientists, and the effect of those alterations or mutations is dictated by nature, not by any scientist. D. Sulston 27; D. Chung 10. 61. Gene sequencing sometimes involves cDNA or complementary DNA. mRNA that is the result of the natural process of transcription (see supra 45) is reverse-transcribed into cDNA. Thus, the coding effect of a cDNA is the same as that of the original DNA from which it was originally derived. Thus, cDNA means a purely coding polynucleotide sequence that is produced from RNA that has had all of its non-coding regions (called introns) removed. D. Leonard 75. 62. Complementary DNA does not exist in the body but is simply a mirror of the RNA which does exist in the body. In the body, certain of the nucleotides, represented by the letters, always bind or attach to certain other nucleotides or letters. G always links to C, and A always links to T. If the RNA in the body is a G, then the cDNA in the lab is a C. Knowing that the cDNA is a C tells a scientist without exception that the RNA was a G. In other words, the cDNA is a sequence of nucleotides that "complements" the RNA. Because the RNA was a mirror of the DNA, the cDNA is again identical to the DNA. The only difference is the introns 15 have been removed. Thus, the functional sequence of the cDNA is identical to the functional sequence of the DNA. D. Mason 28-29, 32. 63. The sequence of a cDNA is dictated not by scientists but by nature. Even though the structure of cDNA does not exist in precisely the same form in the body, for literally all practical and information-based purposes its sequence is identical to that in the body. D. Mason 32. 64. "Isolated DNA" is a fragment of DNA that is separated from other cellular components. This separation could be accomplished through a number of well known techniques. D. Grody 13; D. Leonard 33. 65. "Isolating and purifying" a gene (removing it from the body and placing it in a form so that it can be sequenced and possibly used in other ways) is simply copying it into another format. D. Sulston 26. 66. Gene sequencing is used in diagnostic testing. Gene sequences are examined to determine if they contain any alterations or mutations that have been associated with a particular condition. D. Chung 10; D. Swisher 23-26; D. Mason 21; D. Sulston 24. 67. Scientists often refer to the "wild-type" or "normal" gene, which is the gene without variations. However, the notion that there exists a gene without variations is increasingly misleading. Newfound recognition of the high frequency of variation between individuals has implications for the definition (and patenting) of genes: such variation reinforces the emerging idea that no single DNA sequence can adequately capture either the human genome or a single gene, both of which occur naturally in a variety of forms. D. Mason 17. 68. Gene sequences can have alterations from the wild-type sequence that are caused by nature. D. Chung 10; D. Mason 20; D. Sulston 19, 27; D. Ledbetter 26. 16 69. Full sequencing is often the method used to identify when there is a substitution of one of the letters at a single point or where the insertion or deletion of a small number of bases has occurred. D. Swisher 23. 70. Full sequencing can miss large genomic rearrangements where whole sections of the gene have been deleted or moved to a different part of the sequence. Other tests have been developed that better detect large rearrangements. D. Swisher 23-24; D. Ledbetter 16-17. 71. When alterations or mutations are found in a gene sequence, they can be further investigated to see if they have any significance such as for increasing the propensity to a particular disease. D. Chung 10; D. Sulston 24. 72. The significance of alterations in a gene sequence is caused by nature. D. Chung, 10; D. Mason 20; D. Sulston 27; D. Ledbetter 26. 73. The significance of any person's genetic sequence, including its relationship to any disease, is dictated by nature. D. Mason 32. 74. From the beginning of the Human Genome Project, an international project initiated in 1990 with the aim of sequencing an entire human genome, most scientists and even some private companies recognized the importance of keeping the genome freely available to all. In 1994, the pharmaceutical company Merck funded a massive drive to generate genetic sequences and place them into public databases. D. Sulston 22, 29. 75. In 1996, a group of 50 of the most prominent geneticists in the world who were involved with the sequencing of the human genome adopted the Bermuda principles which included the mandate that all "human genomic sequence information should be freely available and in the public domain in order to encourage research and development and to maximize its benefit to society." D. Sulston 33. 17 BRCA1/2 GENES 76. Mutations on the BRCA1 and BRCA2 genes have been associated with a predisposition to develop breast and ovarian cancer. BRCA1 is a particular portion of DNA found on chromosome 17. BRCA2 is a particular portion of DNA found on chromosome 13. D. Leonard 39. 77. Breast cancer is the most frequently diagnosed cancer worldwide, and is heavily publicized as the leading cause of cancer death for women in Britain and the second leading cause of cancer death for women in the United States. D. Parthasarathy 8. 78. The relationship between mutations in the BRCA1/2 genes and breast and ovarian cancer incidence is complex. Estimates for elevated risk of breast cancer for women who have BRCA1 or BRCA2 mutations have ranged from 3 to 86 percent. Male carriers of mutations are also at increased risk of breast and prostate cancers. D. Love 10; D. Parthasarathy 9. 79. Ovarian cancer is the eighth most common cancer in women and causes more deaths in the Western world than any other gynecologic cancer. D. Swisher 10. 80. Between 10 and 15% of ovarian cancers are inherited genetically. For women who are diagnosed under the age of 50 years old, approximately 80% of inherited ovarian cancers are caused by BRCA1 mutations and approximately 20% are caused by BRCA2 mutations. Women with inherited BRCA1 mutations have a 40-52% cumulative risk of ovarian cancer by the time they reach 70 years old. For women with inherited BRCA2 mutations, the risk is approximately 15-25%. D. Swisher 11. 81. BRCA1/2 mutations and the correlations between the mutations and the increased risk of disease are created by nature. D. Mason 20. 18 82. The existence of BRCA1/2 mutations is an important factor in clinical care of breast and/or ovarian cancer. A patient will not only learn her risk for hereditary breast and ovarian cancer, but also can gain information that may be useful in determining prevention and treatment options. This information is useful for women who are facing difficult decisions regarding whether or not to undergo prophylactic surgery, hormonal therapy, chemotherapy, and other measures. D. Swisher 12; D. Love 8-19. 83. Testing results for the BRCA1/2 genes can be an important factor in structuring an appropriate course of cancer treatment. Certain forms of chemotherapy can be more effective in treating BRCA mutation carriers. D. Swisher 13; D. Love 18. 84. Myriad Genetics offers multiple forms of BRCA1/2 testing to the general public. Its standard test is a full sequencing test called Comprehensive BRACAnalysis. In 2006, it started offering a supplemental test to Comprehensive BRACAnalysis called the BRACAnalysis Rearrangement Test ("BART"). Unless a patient meets certain criteria, the patient must pay an extra fee for BART. Myriad also offers more limited forms of testing. D. Swisher 29-30; D. Reich 10; D. Parthasarathy 26. 85. Many researchers, clinicians, and molecular pathologists have the personnel, equipment, and expertise to sequence and analyze genes, including the BRCA1 and BRCA2 genes. D. Kazazian 11; D. Ganguly 3, 10, 14; D. Chung 11-12, 18; D. Ostrer 8-9; D. Ledbetter 16-18; D. Hegde 8-12; D. Mason 22; D. Kant 5. PATENTS 86. The United States Patent and Trademark Office (USPTO) granted the patent claims at issue in this case. Patent 5,747,282 (Claims 1, 2, 5, 6, 7, and 20), Patent 5,837,492 19 (Claims 1, 6, and 7), Patent 5,693,473 (Claim 1), Patent 5,709,999 (Claim 1), Patent 5,710,001 (Claim 1), Patent 5,753,441 (Claim 1), Patent 6,033,857 (Claims 1 and 2).2 87. 88. Patents prevent anyone from using what has been patented. 35 U.S.C. 271. Uses of the genes at stake in the patent claims in this case include research into or clinical testing of the BRCA1 and BRCA2 genes. D. Sobel 3-5; D. Watson 3-5; D. Ball 2-5; D. Scott 2-5. 89. The patent claims at issue in this case do not claim specific methods of sequencing genes. The patents. 90. If someone had the ability to sequence her own genes, she could utilize non- patented methodologies to sequence those genes, but could be infringing if she sequenced her own BRCA1 and BRCA2 genes. D. Norsigian 7. 91. A patent on a gene sequence and any mutations of that gene applies regardless of the person from whom the gene is taken or the sequencing process that is used. D. Sulston 27. 92. Certain of the patent claims at issue in this case cover the BRCA1 and BRCA2 genes without known alterations or mutations. D. Ravicher, Exs. 1, 6 (Patents `282 (Claims 1, 2, 5, 6) and `492 (Claim 1)). 93. The BRCA1 and BRCA2 genes are naturally-occurring and the sequence of nucleotides in them is created by and dictated by nature. They are products of nature. See supra 40-50. 94. The patents are on wild-type BRCA1 and BRCA2 human genes. None of the claim language covers genes that have been engineered by humans their sequence and function are dictated by nature. D. Grody 10-33, 46-48; D. Leonard 30-53, 66-68. Hereinafter, references to "The patents" includes all of the patents at issue in this case. The patents are attached as Exhibits 1-7 of the Declarations of Daniel B. Ravicher. 2 20 95. The claims that are on genes are on "isolated DNA." Isolated DNA is just a fragment of DNA that has been separated from other things in order to be read. D. Grody 13; D. Leonard 33. 96. The process of sequencing a gene does not change the informational content of that gene. The isolated sequence is informationally and functionally identical to the sequence found inside the body. D. Sulston 27; D. Chung 10; D. Mason 32-33. 97. Certain of the patent claims cover the BRCA1 and BRCA2 genes in their altered or mutated form or gene alterations or mutations. D. Ravicher, Exs. 1, 2, 6 (Patents `473 (Claim 1), `282 (Claim 7), and `492 (Claims 6 and 7)). 98. Some of Myriad's patents cover mutations that were found by other scientists. Myriad filed for a patent on the BRCA2 gene a day before a team of British researchers published the BRCA2 sequence in the scientific journal, Nature. Scientists in the breast cancer genetic community tend to credit this team for being the first to sequence BRCA2 rather than Myriad. D. Sulston 30-32; D. Parthasarathy 12-13. 99. The BRCA1 and BRCA2 gene sequences with mutations are naturally-occurring and products of nature. See supra 51-54, 60-72. 100. The "altered" or "mutated" DNA covered by the patent claims refers to naturally- occurring alterations or mutations in the BRCA1 and BRCA2 genes. D. Grody 37-39, 46-48; D. Leonard 57-59, 66-68. 101. Certain of the patent claims cover "analyzing" or looking at the genes. D. Ravicher, Ex. 3 (Patent `999 (Claim 1)). 102. "Analyzing" a BRCA1 gene sequence for an alteration, as described in `999 cl. 1, simply refers to any method of looking at a BRCA1 nucleotide sequence and inherently presumes 21 that the sequence is already provided. There are numerous methods for looking at or analyzing a sequence. D. Grody 43-45; D. Leonard 63-65. 103. Claim 1 of patent `999 patents looking at the BRCA1 gene for alterations even if that person used a non-patented methodology to do so, including simply looking at a given sequence and thinking about whether it contains an alteration. Patent `999 (Claim 1). 104. Certain of the patent claims cover comparing two genes and then thinking that they are the same or different. D. Ravicher, Exs. 4, 5, 7 ((Patents `001 (Claim 1), `441 (Claim 1), and `857 (Claims 1 and 2)). 105. "Comparing" two genetic sequences, as described in `001 cl. 1, `441 cl. 1, and `857 cls. 1 and 2, means looking at two or more sequences to see if they are different in any way. "Comparing" two sequences inherently presumes that such sequences are already provided. D. Grody 40-42; D. Leonard 60-62. 106. Claim 1 of patents `001, `441, and `857 patent the mental process of comparing two given genetic sequences and thinking "these two genes are the same" or "these two genes are different." D. Ravicher, Exs. 4, 5, 7 (Patents `001 (Claim 1), `441 (Claim 1), and `857 (Claims 1 and 2)). 107. Claim 2 of `857 patents comparing a gene with the wild-type gene, wherein an alteration in the gene indicates a predisposition to breast cancer. D. Ravicher, Ex. 7 (Patent `857 (Claim 2)). 108. Claim 2 of patent `857 patents the mental process of comparing two genes and recognizing that an alteration in the gene "indicates a predisposition to" breast cancer. Id. Patent `857 (Claim 2). 22 109. Patents on correlations or associations between a gene sequence and a greater risk of disease allow the patent holder to control the use of that medical fact. D. Leonard 19. 110. Claim 20 of `282 patents an abstract method for comparing cell growth rates to screen for a possible cancer therapeutic. The claim covers comparing the growth rates of two cells contained an altered BRCA1 gene, one of which has been exposed to the possible cancer therapeutic. Patent `282 (Claim 20). 111. The act of comparing covered by `282 claim 20 means simply looking at two or more things such as cells to determine if there is a difference between them such as growth rates. See D. Grody 40-42; D. Leonard 60-62. 112. Claim 20 of patent `282 patents the mental process of comparing the cell growth rates and "this chemical had a therapeutic impact" on a cell with a BRCA1 altered gene or "this chemical did not have a therapeutic impact." D. Ravicher, Ex. 1 (Patent `282 (Claim 20)). 113. The USPTO granted these patent claims pursuant to a formal written policy that permits the patenting of "isolated and purified" genes and pursuant to a practice that permits such patents and the patenting of correlations created by nature between natural elements of the body and a predisposition to disease. Utility Examination Guidelines, 66 Fed. Reg. 1,093 (Jan. 5, 2001). 114. It is scientifically inaccurate to compare DNA and genes to chemicals. One cannot "invent" a slightly different gene than that which occurs in nature whether natural or mutated in the way that one can invent a slightly different chemical. Because one can invent around chemicals, i.e. can synthetically produce new and better chemicals, but cannot invent around genes, they are not comparable. D. Jackson 12-16, 49. 23 115. The dye that was declared unpatentable in Cochrane v. Badische, 111 U.S. 293 (1884), is scientifically analogous to the patent claims at issue in this case. In both instances, the patent sought was over a product, not a process, and in both instances, the product is functionally identical to the product in nature. D. Jackson 7-16. 116. As with Cochrane, the paper pulp that was declared unpatentable in The Wood- Paper Patent, 90 U.S. 566 (1874), is scientifically analogous to the patent claims at issue in this case. Even though the pulp in that patent was superior in purity to previous wood pulp, it was identical in function. D. Jackson 17-25. 117. The adrenaline that was declared patentable in Parke-Davis and Co. v. H.K. Mulford, 189 F. 95 (S.D.N.Y. 1911), aff'd 196 F.496 (2nd Cir. 1912), is not scientifically analogous to the patent claims at issue in this case because the process for purifying the adrenaline relies solely on human intervention, while genes and their splicing can occur naturally without human intervention. D. Jackson 26-31. 118. The bacteria grouping that was declared unpatentable in Funk Brothers v. Kalo, 333 U.S. 127 (1948), is scientifically analogous to the patent claims at issue in this case because the bacteria grouping, though structurally different from any grouping found in nature, continued to perform in their natural way, just as the patented genes function in the same way as genes in nature. D. Jackson 32-34. 119. The patented B-12 in Merck and Co. v. Olin Mathieson, 253 F.2d 156 (4th Cir. 1958) is not scientifically analogous to the patent claims at issue in this case. The B-12 patent did not cover all uses of B-12 but the patent claims here cover all uses of the genes. In addition, the function of the patented B-12 was different from that found in nature, while the function of the patented genes in this case is identical to that found in nature. D. Jackson 35-37. 24 120. The tungsten that was declared unpatentable in G.E. v. De Forest Radio, 28 F.2d 641 (3rd Cir. 1928), is scientifically analogous to the patent claims at issue in this case. Purification of tungsten was insufficient to alter the fact that the function of the tungsten, like the functions of genes, was dictated by nature and it was therefore unpatentable. D. Jackson 3840. 121. The new bacterium that was declared patentable in Diamond v. Chakrabarty, 447 U.S. 303 (1980), is not scientifically analogous to the patent claims at issue in this case. The bacterium was newly created and genetically engineered. D. Jackson 41. 122. The mathematical algorithms that were declared unpatentable in Parker v. Flook, 437 U.S. 584 (1978) and Gottschalk v. Benson, 409 U.S. 63 (1972) are scientifically analogous to the patent claims at issue in this case. The patent claims in those cases attempted to preclude all uses of the algorithms just as the gene "composition" claims in this case preclude all uses of the genes and the method claims prevent all methods of comparing genes. D. Jackson 42-45, 47-48. 123. The mathematical algorithm that was declared unpatentable in Diamond v. Diehr, 450 U.S. 175 (1981) is not scientifically analogous to the patent claims at issue in this case for the opposite reason. It did not preclude all uses of the algorithm. D. Jackson 46-48. 124. A specific method used to sequence genes is a process that could be patented if it met other patentability requirements. Patents on processes do not apply to the data such as the genes flowing through them. This is analogous to claiming a small thing viewed through the common microscope. D. Leonard 17; D. Sulston 23. 25 ENFORCEMENT OF PATENTS 125. Dr. Kazazian and the University of Pennsylvania received several cease and desist letters from defendant Myriad as a result of work that was being done in the Genetic Diagnostic Laboratory of the Department of Genetics. Dr. Kazazian was also told by defendant Myriad's Chief Science Officer during an in-person meeting that Myriad planned to stop the BRCA testing activity that Dr. Ganguly and he were performing. In November 1998, Myriad sued the University of Pennsylvania for infringing the BRCA patents. Myriad Genetics v. University of Pennsylvania, 2:98-cv-00829 (D. Utah) (filed November 19, 1998). As a result, the laboratory directed by Dr. Kazazian was and is prohibited from doing routine screening for BRCA1 and BRCA2 genes for research or part of clinical practice without Myriad's permission as a direct result of the patents challenged by this action. D. Kazazian 4-7; D. Ganguly 4-10; D. Parthasarathy 28. 126. Dr. Kazazian and Dr. Ganguly were screening for BRCA mutations using a different methodology than that used by Myriad, but were precluded from using that methodology by Myriad because the patents are on the genes themselves, not on the methodology for screening. D. Kazazian 9; D. Parthasarathy 23. 127. Myriad sent a letter to Barbara Weber, principal investigator on a project sponsored by the National Cancer Institute, regarding how Myriad's patent position might impact research sponsored by the Institute. As a result of that letter, the University of Pennsylvania laboratory that was doing BRCA analyses for Dr. Weber, stopped doing those analyses. D. Ganguly 12. 128. Myriad sent a letter to Georgetown University demanding that Georgetown stop sending genetic samples to the University of Pennsylvania laboratory. As a result of that letter, 26 the University of Pennsylvania laboratory that was doing BRCA analyses for Georgetown stopped doing those analyses. D. Ganguly 13. 129. Myriad and Oncormed, another company that undertook BRCA-related activity, were involved in a series of lawsuits against each other regarding patents that covered various aspects of the BRCA1 gene sequence. D. Parthasarathy 27. 130. Sometime in or around December 2000, the director of the Yale DNA Diagnostics Lab received a cease and desist letter from Myriad concerning BRCA1/2 genes. As a result of that letter, Yale ceased doing BRCA1/2 testing. D. Matloff 7. 131. In 2005, Ms. Matloff contacted Myriad to obtain permission so that the Yale DNA Diagnostic Lab could do screening for mutations caused by large rearrangements, which Myriad was not then doing. Myriad denied permission. D. Matloff 8. 132. Myriad wrote to Dr. Ostrer prohibiting him from engaging in any BRCA1 or BRCA2 testing unless he entered a license, and even then the company would only allow him to do all but the most limited BRCA1 and BRCA2 testing. Dr. Ostrer refused that license because it was too narrow to allow him to do any meaningful BRCA-related activity. D. Ostrer 7. 133. A valid scientific survey of laboratory directors in the United States revealed that 25% had stopped performing a clinical test because of a gene patent or license. D. Cho 11-15. 134. A valid scientific survey of laboratory directors in the United States revealed that of those who stopped performing a clinical test because of a gene patent or license, the largest number stopped doing BRCA1 and BRCA1 testing (and the same number stopped ApoE testing). D. Cho 16. 135. Nine labs reported that they had stopped performing tests for BRCA1 and BRCA2 in response to a valid scientific survey of laboratory directors in the United States. D. Cho 16. 27 136. Labs have avoided or refrained from developing tests for BRCA1 or BRCA2 as a direct result of the gene patents held by Myriad. D. Ostrer 6; D. Ledbetter 14-16. 137. Other studies of other gene patents also reveal that labs frequently stop developing or offering clinical tests for disease as a result of gene patents. In a valid scientific survey of labs in the United States, 26% stopped doing testing for hemochromatosis as a result of gene patents. D. Cho 17-20. 138. Researchers, clinicians, and pathologists are aware that Myriad has sent cease and desist letters over the patent claims at issue in this case or are aware that it prohibits virtually all clinical testing of the BRCA1/2 genes. D. Kazazian 5-11; D. Ganguly 4-14; D. Chung 15; D. Hegde 10; D. Matloff 5-7; D. Ostrer, 4-7; D. Swisher 28; D. Hubbard 7-8; D. Kant 4; D. Ledbetter 13; D. Reich 3, 5; D. Parthasarathy 28-31. 139. Researchers, clinicians, and pathologists are prohibited from sequencing and analyzing the BRCA1 and BRCA2 genes because of the patents at issue in this case. D. Ganguly 14; D. Chung 13, 17, 18; D. Ostrer 6-8; D. Hegde 10; D. Swisher 34-35; D. Hubbard 9; D. Kant 6; D. Ledbetter 16, 18; D. Reich 3, 5. 140. Myriad does not permit researchers to tell patients involved in research the results of their BRCA1/2 testing. D. Ostrer 10; D. Chung 13. 141. The BRCA1/2 patents prevent physicians from testing for breast and ovarian cancer genetic risk (BRCA1/2 sequencing). D. Leonard 14; D. Swisher 34. EFFECTS OF BRCA1/2 GENE PATENTS 142. For a period of years, the testing done by Myriad did not reveal all known mutations in the BRCA1 and BRCA2 genes or utilize known methodologies that would have 28 revealed those additional mutations. D. Chung 19; D. Matloff 8; D. Swisher 26; D. Limary 7; D. Thomason 6; D. Raker 7-8; D. Ledbetter 16; D. Parthasarathy 29. 143. During this period, people who received Myriad's test may have gotten false negative results. A scientifically valid study from 2006 concluded that 12% of those from high risk families with breast cancer and with negative test results from Myriad carried cancerpredisposing genomic deletions or duplications in one of those genes. This result reinforced other similar studies done over the years. D. Swisher 25-26. 144. The Myriad test that Ms. Thomason, Ms. Raker, and Ms. Limary received did not look for all known large rearrangements in the BRCA genes. D. Thomason 6; D. Raker 7-8; D. Limary 7. 145. Myriad now offers a separate test called BART which looks for additional large rearrangements in the coding sequences of both BRCA1 and BRCA2. This test is offered with the standard test for a limited number of women, but most women must pay an extra fee for it. D. Swisher 29-30; D. Reich 10; D. Matloff 14. 146. The BART test is not available to many women who should have access to it as a result of the strict criteria Myriad has adopted and the price Myriad charges for the test. Myriad's standard way of offering genetic testing is a partial testing strategy because it does not reflexively offer large rearrangement testing for all women who receive negative full sequencing test results. D. Swisher 30-31, 33; D. Reich 10; D. Matloff 14; D. Ledbetter 16. 147. The sensitivity and specificity of BART has never been fully and independently validated. D. Swisher 32. 29 148. Other methods for looking for BRCA large rearrangements, such as one called MLPA, are performed around the world. Myriad has never published comparisons of BART with MLPA. D. Swisher 33. 149. Other labs are in a position to offer more comprehensive testing than Myriad's standard test and would do so were it not for Myriad's patents. Some labs would use newer testing methods (such as microarray analysis) that are expected to result in improved testing quality and efficiency. Other labs would reflexively conduct large rearrangement testing after a negative test result is received through full sequencing. D. Ledbetter 17-18; D. Chung 18; D. Ostrer 9. 150. In the event the patents were invalidated, other labs would immediately consider and/or begin offering genetic testing to include all known methods of analysis of the genes. D. Ledbetter 18; D. Ostrer 9; D. Kant 6; D. Hegde 10-11; D. Chung 17-18; D. Hubbard 9; D. Ganguly 14. 151. When Ms. Limary was tested by Myriad, she was given the following test result: "genetic variant of uncertain significance." D. Limary 5. 152. Variants of uncertain significance in the BRCA1 and BRCA2 genes are reported disproportionately for members of minority groups. D. Chung 20; D. Ostrer 12; D. Matloff 9; D. Limary 8. 153. A lack of independent BRCA1/2 testing and analysis undermines the ability of the scientific community to determine the meaning of variants of uncertain significance. Other labs would do extensive analyses for patients in the face of a result of "variant of uncertain significance." D. Chung 21; see D. Ostrer 12. 30 154. Myriad does not routinely perform genetic testing on tumor specimens preserved in paraffin from deceased family members, even though such testing can often provide valuable genetic information for living relatives and is often necessary for accurate test interpretation. Such testing could be performed in other research laboratories and would be, were it not for the patents issue in this case. D. Chung 24. 155. Because only Myriad performs full sequencing in the United States, women who receive a negative result cannot know for certain what the rate of false negatives might be. Women who receive a positive result cannot confirm the lab's findings or seek a second opinion on the interpretation of those results. D. Ledbetter 23; D. Ostrer 11. 156. After receiving a test from Myriad that indicated she was positive for a deleterious mutation on her BRCA2 gene, Ms. Girard sought confirmatory testing of that test result but learned that Myriad is the only laboratory in the country that may provide full sequencing. The patents on the BRCA genes block her from getting a second full sequencing test done. Ms. Girard has been forced to make significant medical decisions for herself based on a test result that has not been verified by another laboratory. A second opinion on Ms. Girard's test results is also crucial for her immediate family's options and screening. D. Girard 4-9. 157. BRCA genetic testing is one of the very few tests performed as part of breast cancer care and prevention for which a doctor or patient cannot get a second confirmatory test done through another laboratory. D. Love 12. 158. Before taking major surgical steps, Ms. Ceriani would want a second opinion concerning her BRCA1/2 status. D. Ceriani 9, 11. 159. Fortune 7. Ms. Fortune would want a second opinion concerning her BRCA1/2 status. D. 31 160. Other pathologists, clinical laboratory scientists, medical professionals, and researchers could provide the testing now done by the patent holders at a cost less than that charged by the patent holders. D. Kazazian 8; D. Matloff 12, 14; D. Ostrer 8; D. Reich 6, 8, 13. 161. The BRCA1/2 testing being done by Yale DNA Diagnostics Lab prior to receipt of Myriad's cease and desist letter cost less than Myriad charges. D. Matloff 7. 162. The BRCA1/2 testing being done by the University of Pennsylvania Genetic Diagnostic Laboratory prior to receipt of Myriad's cease and desist letters cost less than Myriad charges. D. Kazazian 8. 163. The BRCA1/2 testing offered by OncorMed was cheaper for patients than the testing offered by Myriad. D. Parthasarathy 24. 164. Ms. Ceriani's genetic counselor submitted a blood sample to Myriad on her behalf. However, Ms. Ceriani was notified that Myriad would not process the sample. Even though Ms. Ceriani's insurance company, MassHealth, has informed her that it would cover the BRCA genetic test, Myriad will not accept the MassHealth coverage. Ms. Ceriani is unable to pay the full cost out-of-pocket and, to date, has not been tested. D. Ceriani 5-7. 165. Ms. Fortune is insured through Medi-Cal. Her oncologist and genetic counselor recommended that she obtain BRCA1/BRCA2 genetic testing but told her that Myriad would not accept her insurance. Ms. Fortune is unable to pay the full cost out-of-pocket and, to date, has not been tested. D. Fortune 4-5. 166. Myriad's BART test is not covered by many insurers, and for most patients, they must pay separately for BART on top of the fee for the standard Comprehensive BRACAnalysis test. D. Reich 10. 32 167. Ms. Raker's genetic counselor advised her about additional BRCA genetic testing that looks for other large genetic rearrangements that are not included in Myriad's standard full sequencing test, but informed her that it was unclear whether her insurance would cover the cost of that test. Ms. Raker is unable to afford the extra cost and, to date, has not received this testing. Without these results, she cannot determine the best course of medical care for herself. D. Raker 7-11. 168. Ms. Thomason has not been able to afford the additional BRCA testing recommended by her genetic counselor. D. Thomason 8. 169. Genetic counselors would recommend additional women for testing and additional tests if the cost came down. D. Matloff 13-14; D. Reich 6-13. 170. Sulston 36. 171. The Breast Cancer Information Core (BIC), an international resource, is an open Data sharing is key to the future of genetic discoveries and bioinformatics. D. access, on-line database that is a central repository for information about BRCA genes and BRCA genetic variants. It helps facilitate identification of deleterious mutations (mutations associated with a higher risk of cancer) and provides a mechanism to collect and distribute data about genetic variants. The value of the BIC comes from the amount and quality of data provided by the scientific community. D. Swisher 15, 17; D. Chung 22; D. Ostrer 13. 172. By gathering information about variants of uncertain significance in one place, the BIC plays an important role in helping to elucidate these variants. D. Swisher 18. 173. 174. Myriad does not share its data with BIC. D. Swisher 19. If other researchers had access to the data Myriad has collected as a result of its exclusive testing, additional information about the nature of the BRCA1/2 variants and their 33 significance might be known. D. Sulston 36; D. Swisher 20-21; D. Matloff 9; D. Ostrer 12-13; D. Chung 21-22; D. Ledbetter 20. 175. 176. Gene patents inhibit research. D. Sulston 37; D. Cho 24. A scientifically valid survey of laboratory directors in the United States revealed that 53% decided not to develop a new clinical test because of a gene patent or license, 67% believed that gene patents decreased an ability to do research. A second study concluded that 46% of respondents believed that gene patents delayed or limited their research. D. Cho 10. 177. Gene patents are deleterious to unraveling the role of genes in medical conditions. D. Sulston 38. 178. New sequencing technologies are beginning to offer the option of faster and less expensive sequencing of single genes, multiple genes, and even the entire human genome. Patents on one or more genes may impede scientists' ability to develop a comprehensive test for complex diseases or provide a person with an analysis of his or her entire genome. D. Sulston 38; D. Ledbetter 24. 179. Gene patents directly interfere with the ability of physicians and researchers to investigate complex diseases. For example, BRCA1 and BRCA2 may be associated with cancers other than breast and ovarian cancer, or even other diseases, but so long as the patents on these genes remain, no one will be able to include these genes in tests for other disease predispositions. D. Ledbetter 24-25. 180. Imagine if Watson and Crick had patented the double-helix structure when they discovered it. D. Parthasarathy 28. 181. Gene patents inhibit clinical diagnostic laboratories from providing clinical tests and services. D. Cho 24. 34 182. Geneticists have refrained from developing and improving tests for diseases as a result of the impediment of gene patents. D. Ledbetter 14-15. 183. Gene patents are not necessary to create incentives for initial discoveries or the development of commercial applications, including diagnostics. D. Cho 25; D. Leonard 2021. 184. Patents have not been necessary for rapid introduction of genetic testing. Clinical genetic testing has been offered for genetic testing prior to a patent being issued. D. Cho 21. 185. A study of gene patents issued in the U.S. for genetic diagnostics showed that 67% of these patents were issued for discoveries funded by the U.S. government. D. Cho 22. 186. Another study showed that 63% of patents on gene sequences resulted from federally supported research. D. Leonard 22. 187. Significant federal funds were provided to support research to find the BRCA genes. The National Institutes of Health (NIH) funded a six-person National Institute of Environmental Health Sciences research team. NIH also provided approximately $2 million in research grants to the University of Utah for this research. NIH contributed one-third of the funding for BRCA1's discovery. D. Parthasarathy 18. 188. Patient care is promoted where more than one lab offers a particular genetic test utilizing different methodologies. D. Ostrer 11; D. Swisher 32-35; D. Leonard 24. 189. It is important for more than one lab to offer a particular genetic test in order to ensure that the testing being done is quality testing and the results are accurate. D. Chung 23; D. Swisher 32-35; D. Ledbetter 23; D. Reich 9, 11; D. Leonard 24; D. Parthasarathy 29, 31; D. Ostrer 11. 35 190. More than one lab should offer a particular genetic test because clinical laboratory testing takes place in a broader context of patient care and services. Allowing only one lab to offer testing means that one lab dictates the standards for patient care in testing for that disease. D. Parthasarathy 30, 31. 191. Research should allow for subjects to be told the results of their genetic testing as this can lead to valuable insights concerning their behavior. D. Ostrer 10. 192. Ethical standards require that physicians be able to provide genetic test results to research subjects, where such results are requested. D. Chung 14. EFFECT OF PATENTS ON PLAINTIFFS 193. AMP sues on behalf of its members, some of whom are ready, willing, and able to engage in research and clinical practice involving the BRCA1 and BRCA2 genes if the patents are invalidated. D. Sobel 3; D. Hegde 6-12. 194. ACMG sues on behalf of its members, some of whom are ready, willing, and able to engage in research and clinical practice involving the BRCA1 and BRCA2 genes if the patents are invalidated. D. Watson 3; D. Chung 4, 17-18; D. Ostrer 3, 8-9; D. Ledbetter 4, 18. 195. ASCP sues on behalf of its members, some of whom are ready, willing, and able to engage in research and clinical practice involving the BRCA1 and BRCA2 genes if the patents are invalidated. D. Ball 2; D. Hubbard 2. 196. CAP sues on behalf of its members, some of whom are ready, willing, and able to engage in research and clinical practice involving the BRCA1 and BRCA2 genes if the patents are invalidated. D. Scott 3; D. Kant 4-6. 197. The laboratory of Dr. Haig Kazazian and Dr. Arupa Ganguly at the University of Pennsylvania has all of the resources and technological capability to offer BRCA testing. If the 36 patents are invalidated, they would immediately consider resuming BRCA testing. D. Kazazian 11; D. Ganguly 14. 198. Dr. Wendy Chung's laboratory at Columbia University has the personnel, expertise and facilities to do BRCA sequencing. If the patents are invalidated, she would offer clinical testing of the BRCA genes, including BRCA testing that is more comprehensive than that which Myriad offers. Dr. Chung would be in a position to tell the subjects in her research their genetic test results. Her lab would share the results of its work with the BIC database. D. Chung 17-18. 199. Dr. Harry Ostrer's laboratory at New York University has the personnel, expertise and facilities to do BRCA sequencing. If the patents are invalidated, he would offer clinical testing of the BRCA genes. He would inform participants in his research program about the results of their BRCA1/2 genetic screening. His lab would share the r