Case 1:09-cv-04515-RWS Document 158 Filed 12/23/09 Page 1 of 33
`
`UNITED STATES DISTRICT COURT
`FOR THE SOUTHERN DISTRICT OF NEW YORK
`
`~SSOCIA TION FOR MOLECULAR PATHOLOGY;
`~MERICAN 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;
`iKA THLEEN RAKER,
`
`Plaintiffs,
`
`-against-
`
`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
`r..-C'+t.. ...... T T-;-.cu:'lt.-... ..... ~..;......,T i""t.+T T+nh Da.~.an'W"roh Pn.nnrln.f~rt.'M
`U1_ UlCi UlllV~al:).llJ Vl. l.JlUl.l _l_~\o..t.:)\o..tU.L\.111 .L VU.l.l\..I.U'-_l_VJ.-1'
`
`Defendants.
`
`No. 09 Civ. 4515
`(RWS)
`
`ECF Case
`
`DECLARATION OF
`DR. GREGORY C.
`CRITCHFIELD
`
`I, Gregory C. Critchfield, declare:
`
`1.
`
`I am President of Myriad Genetic Laboratories, Inc., a wholly owned
`
`subsidiary of Myriad Genetics, Inc. (referred together as "Myriad"). I have held this
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`position since July 1998. I received my M.D. from the University of Utah, and my M.S.
`
`in Biophysical Sciences from the University of Minnesota. I am Board Certified in
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`Clinical Pathology. Before joining Myriad, I served as Senior Vice President, Chief
`
`1
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`GeneDX 1014, pg. 1
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`Case 1:09-cv-04515-RWS Document 158 Filed 12/23/09 Page 2 of 33
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`Medical and Science Officer of Quest Diagnostics Inc. A copy of my curriculum vitae
`
`and a list of publications by me are provided in the Exhibits 1 and 2, respectively.
`
`I. MYRIAD'S PATENT RIGHTS HAVE PROMOTED RESEARCH
`
`2.
`
`Myriad was founded to conduct innovative research to discover and isolate
`
`disease genes, and to commercialize genetic testing based on the disease genes. Today
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`Myriad is still active in research and discovery to develop prognostic, personalized, and
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`predictive medicine testing products. It is in Myriad's own interest that neither basic nor
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`clinical research be stifled by patents. In fact, Myriad has consistently promoted and
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`encouraged both basic and clinical research on the BRCAJ and BRCA2 genes by others,
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`by (1) allowing academic scientists to conduct research studies on the BRCAJ and
`
`BRCA2 genes freely; (2) providing direct assistance to researchers in their studies on the
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`BRCAJ and BRCA2 genes; and (3) conducting its own research on the BRCAJ and
`
`BRCA2 genes, publishing the research results and actively disseminating information on
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`the BRCAJ and BRCA2 genes.
`
`Myriad Allows Research on the BRCAJ and BRCA2 Genes Freely
`
`3.
`
`It has been, and still is, Myriad's policy and practice to allow scientists to
`
`conduct research studies on the BRCAJ and BRCA2 genes freely. This has been
`
`commonly understood by academic scientists in the field. For example, Plaintiff Wendy
`
`Chung acknowledges that researchers "could sequence the BRCAJ and BRCA2 genes for
`
`purely research purposes." D. Chung ,-r 15. In fact, Dr. Chung has been doing so. See
`
`e.g., D. Chung ,-r 11 ("As part of my molecular genetics research, we sequence human
`
`genes, including the BRCAJ and BRCA2 genes of research subjects in my research lab.
`
`We look at the sequences to determine if there are any alterations and investigate whether
`
`2
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`GeneDX 1014, pg. 2
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`

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`Case 1:09-cv-04515-RWS Document 158 Filed 12/23/09 Page 3 of 33
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`those alterations have clinical significance."). Indeed, tens of thousands of researchers
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`have been conducting research on the BRCAJ and BRCA2 genes and published thousands
`
`of research papers on the BRCAJ and BRCA2 genes. See ~ 13 below; see also, D. Parvin;
`
`D. Li; D. Baer; D. Sandbach.
`
`Myriad Provides Direct Assistance to Researchers in Their Studies
`
`4.
`
`Myriad and its collaborators published their landmark research on the
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`BRCAJ and BRCA2 genes in 1994 and 1996, respectively. Since then, Myriad has
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`provided assistance to researchers around the world in their independent studies on the
`
`genes.
`
`5.
`
`Since 1994, Myriad has provided genetic materials such as eDNA clones
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`of the BRCAJ and BRCA2 genes free to researchers at over 30 research institutions all
`
`over the world, including, among others, the University of Pennsylvania, Emory
`
`University, the University of Chicago, and the University of Rochester. These
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`researchers have since published a total of 336 peer-reviewed scientific papers related to
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`BRCAJ and BRCA2.
`
`6.
`
`Myriad also has a policy to collaborate with researchers on studies relating
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`to the BRCAJ and BRCA2 genes. In fact, since the BRCAJ and BRCA2 genes were
`
`discovered, Myriad has collaborated with over 440 outside researchers and participated in
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`more than 110 research programs/studies by outside researchers in further studies of
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`BRCA 1 andBRCA2.
`
`7.
`
`For example, in 1999, to further encourage research on the BRCAJ and
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`BRCA2 genes, I proposed to Dr. Richard Klausner, the then National Cancer Institute
`
`("NCI") Director, for Myriad to provide BRCA testing services to researchers conducting
`
`3
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`GeneDX 1014, pg. 3
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`

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`Case 1:09-cv-04515-RWS Document 158 Filed 12/23/09 Page 4 of 33
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`studies funded by NCI and other NIH Institutes. In December 1999, a Memorandum of
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`Understanding (MOU) between Myriad and NCI was signed. Under the MOU, Myriad
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`agreed to provide research testing services at a fraction of the commercial testing price to
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`researchers conducting research funded by NCI or another Institute under the National
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`Institute of Health. The MOU was renewed twice for a total of six years. During those
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`six years, 178 scientists received the discounted research testing services and 5,932
`
`individuals were tested for BRCA mutations under the MOU. This program provided
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`support for a number of key research groups that led to important publications on BRCA
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`mutation prevalence and the value of clinical intervention in BRCA mutation carriers.
`
`8.
`
`In another important area, Myriad worked with noted researchers on
`
`efforts to classify genetic variants of uncertain clinical significance ("VUS"), making
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`data available from our large sequence database. 1 In these studies, Myriad provided the
`
`researchers with information from its database of gene sequence information built upon
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`the largest scale of clinicai genetic testing on BRCAJ and BRCA2 in the world. This was
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`critical to the researchers' studies. The published research results have the potential of
`
`improving the diagnostic testing for a number of other genes.
`
`9.
`
`Myriad's contribution to research is also evidenced by the tens of millions
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`of dollars in patent royalty payments made to research institutions such as the University
`
`ofUtah, National Institute of Health, the University of Pennsylvania, the University of
`
`Toronto, and Laval University, all of which collaborated with Myriad in research to
`
`identify and isolate the BRCAJ and BRCA2 genes.
`
`1 See e.g., Abkevich et al., Analysis of Missense Variation in Human BRCAl in the Context of Interspecific
`Sequence Variation, J. MED. GENET., 40:492-507 (2004); Goldgar et al. & Breast Cancer Information Core
`(BIC) Steering Committee, Integrated Evaluation of DNA Sequence Variants of Unknown Clinical
`Significance: Application to BRCAl andBRCA2, AM. J. MED. GENET., 75:535-544 (2004).
`
`4
`
`GeneDX 1014, pg. 4
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`Case 1:09-cv-04515-RWS Document 158 Filed 12/23/09 Page 5 of 33
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`Myriad Actively Publishes Its Own Research and
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`Disseminates Scientific Information on the BRCAJ and BRCA2 Genes
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`10.
`
`Besides assisting outside researchers in their research, Myriad also has
`
`been actively conducting its own research for a better understanding of the BRCAJ and
`
`BRCA2 genes. More importantly, Myriad has been actively publishing its research
`
`findings in peer-reviewed journals, and abstracts and posters in scientific meetings. To
`
`date, Myriad has made 128 publications on the BRCAJ and BRCA2 genes in peer-
`
`reviewed journals and scientific meetings.
`
`11.
`
`Shortly after the discoveries of the BRCA genes by Myriad and its
`
`collaborators, Myriad, under no obligation to do so, worked with other researchers to
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`build the Breast Cancer Information Core ("BIC") database
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`(http:/ /www.research.nhgri.nih.gov/bicD, a central repository for information regarding
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`BRCA mutations. The BIC database is an open access on-line database that provides
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`valuable information to scientists in their early research on the BRCAJ and BRCA2 genes.
`
`Myriad is the largest contributor to this database, and made more than 20,000
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`submissions to the database.
`
`12.
`
`In addition, Myriad has published the most clinical data on mutation risk
`
`in the BRCAJ and BRCA2 genes based on its extensive experience from the largest scale
`
`of genetic testing ever conducted in the world? The mutation risk data have been
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`tabulated and posted on Myriad's website
`
`(http://www.myriadtests.com/provider/mutprevo.htm), and are frequently updated by
`
`Myriad and freely available to researchers and clinicians throughout the world. Using
`
`these mutation prevalence tables, researchers and physicians can readily determine an
`
`2 See Frank et al., Clinical Characteristics of Individuals with Germline Mutations in BRCA 1 and BRCA2:
`Analysis of 10,000 Individuals, J. CLIN. ONCOL., 20:1480-90 (2002).
`
`5
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`GeneDX 1014, pg. 5
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`Case 1:09-cv-04515-RWS Document 158 Filed 12/23/09 Page 6 of 33
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`individual's predicted risk of harboring a deleterious BRCA mutation based on his or her
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`personal cancer history and family history. See Exhibit 3. These tables have been widely
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`accessed by researchers and clinicians worldwide.
`
`Significant Progress Has Been Made in Research on the BRCA Genes
`
`13.
`
`Scientific research in BR CA -associated hereditary breast and ovarian
`
`cancers not only has been made possible by the landmark discoveries and publications by
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`Myriad and its collaborators, but also has been significantly promoted by Myriad's policy
`
`and practice as summarized above. Indeed, a recent search of the PubMed medical
`
`literature database shows that since Myriad's publications of the discoveries of the
`
`BRCAJ and BRCA2 genes in October, 1994,3 and March 1996,4 respectively, more than
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`18,000 scientists have researched the BRCA genes, publishing more than 5,600 research
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`papers on BRCAJ and over 3,000 research papers on BRCA2. Many ofthese scientists
`
`are members of the institutional Plaintiffs in this suit including the Association for
`
`Molecular Pathology, American College of Medical Genetics, American Society for
`
`Clinical Pathology, and College of American Pathologists. Among these scientists are
`
`also members of amici supporting the Plaintiffs' case including the American Medical
`
`Association, American Society of Human Genetics, American College of Obstetricians
`
`and Gynecologists, American College of Embryology, and the Medical Society of the
`
`State ofNew York. Notably, the individual plaintiffs in this suit and their supporting
`
`3 Mild eta!., A Strong Candidate for the Breast and Ovarian Cancer Susceptibility Gene BRCA1, SCIENCE,
`266:66-71 (1994).
`4 Tavtigian eta!., The Complete BRCA2 Gene and Mutations in Chromosome 13q-Linked Kindreds, NAT.
`GENET., 12:333-7 (1996).
`
`6
`
`GeneDX 1014, pg. 6
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`Case 1:09-cv-04515-RWS Document 158 Filed 12/23/09 Page 7 of 33
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`declarants alone have published a total of 48 peer-reviewed research papers on the
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`BRCAJ and BRCA2 genes. See Exhibit 4.
`
`14.
`
`Thanks in part to Myriad's active effort in promoting research, scientists
`
`have made impressive progress in understanding and even harnessing the BRCAJ and
`
`BRCA2 genes. For example, when Myriad and its collaborators identified and isolated
`
`the BRCAJ and BRCA2 genes, the data showing their association with predisposition to
`
`cancer was generated from selected Caucasian family pedigrees. Researchers now know
`
`that mutations in the BRCAJ and BRCA2 genes confer high risk for hereditary breast and
`
`ovarian cancer in a variety ofhuman population groups. 5 Also, when the genes were
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`discovered, the biological mechanism underlying their association with cancer was
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`unknown. Today, scientists understand that functional BRCA1 and BRCA2 proteins
`
`prevent mutations and cancer through homologous recombination by repairing double-
`
`stranded DNA damages.6
`
`15.
`
`Importantly, extensive clinical research has uncovered various means to
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`reduce the risk of breast and ovarian cancer once BRCA mutations carriers are identified.
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`For example, the risk of breast cancer can be reduced by up to 90% by prophylactic
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`mastectomy in BRCA mutation carriers. 7 The risk of breast cancer can be reduced as
`
`5 See James D. Fackenthal & Olufunmilayo I. Olopade, Breast Cancer Risk Associated with BRCA1 and
`BRCA2 in Diverse Populations, NAT. REV. CANCER, 7:937-948 (2007).
`6 See e.g., Gowen et al., BRCA1 Required for Transcription-Coupled Repair of Oxidative DNA Damage,
`SCIENCE, 281: 1009-12 (1998); W elcsh et al., Insights into the functions ofBRCA 1 and BRCA2, TRENDS
`GENET., 16:69-74 (2000).
`7 See e.g., Hartmann et al., Efficacy of Bilateral Prophylactic Mastectomy in BRCA1 andBRCA2 Gene
`Mutation Carriers, J. NAIL. CANCER INST., 93:1633-7 (200 1 ); Reb becket al., Bilateral Prophylactic
`Mastectomy Reduces Breast Cancer Risk in BRCA1 andBRCA2 Mutation Carriers: the PROSE Study
`Group, J. CLIN. ONCOL., 22:1055-62 (2004).
`
`7
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`GeneDX 1014, pg. 7
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`Case 1:09-cv-04515-RWS Document 158 Filed 12/23/09 Page 8 of 33
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`much as 72% by prophylactic oophorectomy in BRCA2 mutation carriers. 8 The risk for
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`ovarian cancer is reduced by 85-96% by prophylactic risk- reducing oophorectomy in
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`BRCA mutation carriers.9 In addition, mortality risk can be significantly reduced by
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`bilateral prophylactic risk-reducing salpingo-oophorectomy in BRCA mutation carriers. 10
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`Also, tamoxifen use in BRCA mutation carriers for five years reduces the odds of
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`contralateral breast cancer by 50%. 11 Finally, researchers have also found that the use of
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`oral contraceptives for at least six years is associated with a 60% decreased risk of
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`ovarian cancer. 12
`
`16.
`
`Exciting research on the BRCA genes has also suggested improved and
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`personalized chemotherapies in cancer patients. For example, scientists have found that
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`breast cancer tumors must possess intact BRCA function in order to exhibit sensitivity to
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`spindle poisons such as taxol and vinblastin, while tumors lacking BRCA function
`
`exhibit increased sensitivity to cytotoxic DNA-damaging agents such as cisplatin. 13
`
`17.
`
`Indeed, new drugs such as PARPl inhibitors are being deveioped targeting
`
`the biological pathway centering around BRCA1 and BRCA2 proteins in cancer
`
`cells. Examples of such PARP1 inhibitor drugs in development include olaparib (also
`
`8 See e.g., Kauff et al., Risk-Reducing Salpingo-Oophorectomy for the Prevention ofBRCA1- andBRCA2-
`Associated Breast and Gynecologic Cancer: A Multicenter, Prospective Study, J. CLIN. ON COL., 26:1331-7
`(2008).
`9 See e.g., Rebbeck et al., Prophylactic Oophorectomy in Carriers ofBRCA1 or BRCA2 Mutations, N.
`ENGL. J. MED., 346:1616-22 (2002).
`10 See e.g., Domchek et al., Mortality after Bilateral Salpingo-Oophorectomy in BRCA1 andBRCA2
`Mutation Carriers: A Prospective Cohort Study, LANCET ONCOL., 7:223-9 (2006).
`11 See e.g., Narod et al., Tamoxifen and Risk of Contralateral Breast Cancer in BRCA1 andBRCA2
`Mutation Carriers: A Case-Control Study, LANCET, 356:1876-1881 (2000).
`12 See e.g., Narod et al. Oral Contraceptives and the Risk of Hereditary Ovarian Cancer, N. ENGL. J. MED.,
`339:424-428 (1998).
`13 See e.g., Kennedy et al., The Role ofBRCA1 in the Cellular Response to Chemotherapy, J. NAIL.
`CANCER INST., 96:1659-68 (2004); Farmer et al., Targeting the DNA Repair Defect in BRCA Mutant Cells
`as A Therapeutic Strategy, NATURE, 434:917-21 (2005).
`
`8
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`GeneDX 1014, pg. 8
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`Case 1:09-cv-04515-RWS Document 158 Filed 12/23/09 Page 9 of 33
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`known as AZD2281) by AstraZeneca14, BSI-201 by BiPar Sciences Inc. 15, ABT-888 by
`
`Abbott Laboratories, Inc. 16, and AG014699 by Pfizer17. Screening for BRCAJ and
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`BRCA2 mutations can allow such drugs to be administered specifically to cancer patients
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`harboring such mutations. This personalized approach provides patients with optimized
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`treatment while avoiding wasteful spending on ineffective therapies. As a matter of fact,
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`Myriad has been using its expertise in BRCA mutation screening to help AstraZeneca in
`
`its development of olaparib, which has shown great promise in clinical trials.
`
`18.
`
`In summary, tremendous progress has been made in the field of BRCAJ
`
`and BRCA2 and hereditary breast and ovarian cancer. Because of all the research in this
`
`area, physicians today are able to conveniently estimate the risk of BRCA mutation in a
`
`given individual, and identify candidates for BRACAnalysis® testing. Moreover, once
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`BRCA mutations are detected, effective options validated by research are available to
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`reduce the risk of breast and ovarian cancer in healthy individuals or the risk of second
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`cancer in cancer patients. In addition, tailored chemotherapy regimens can be seiected
`
`for cancer patients based on the BRCA mutation status. More excitingly, effective
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`PARP1 inhibitors targeting tumors with BRCA mutation are on the horizon. Myriad's
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`discovery and publication ofthe BRCAJ and BRCA2 genes opened the doors to all of
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`these advances in science. Myriad's policy and practice of promoting research has
`
`14 Fong eta!., Inhibition ofPoly(ADP-ribose) Polymerase in Tumors from BRCA Mutation Carriers, N.
`ENGL. J. MED., 361:123-34 (2009).
`15 Kopetz et al., First in Human Phase I Study Of BSI-201, A Small Molecule Inhibitor of Poly ADP-Ribose
`Polymerase (PARP) in Subjects with Advanced Solid Tumors, J. CLlN. ONCOL., 26: 2008 (May 20 suppl;
`abstr 3577).
`16 Yang et al., Immunohistochemical Detection of Poly(ADP-Ribose) Polymerase Inhibition by ABT-888 in
`Patients with Refractory Solid Tumors and Lymphomas, CANCER BIOL. THER., 8:2002-7 (2009).
`17 Plummer et al., Phase I Study of the Poly(ADP-Ribose) Polymerase Inhibitor, AG014699, in
`Combination with Temozolomide in Patients with Advanced Solid Tumors, CLIN. CANCER REs., 14:7917-23
`(2008).
`
`9
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`GeneDX 1014, pg. 9
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`Case 1:09-cv-04515-RWS Document 158 Filed 12/23/09 Page 10 of 33
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`facilitated such significant progress in science and medicine. The notion advanced by the
`
`Plaintiffs that research has been stifled by the patents at issue in this lawsuit is
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`contradicted by the evidence.
`
`Myriad Has Never Stopped Scientists from Doing Research
`
`19.
`
`In the late 1990s, Myriad sent cease and desist letters to the University of
`
`Pennsylvania regarding the commercial (not research) BRCA testing activities of Drs.
`
`Haig Kazazian and Arupa Ganguly at the Genetic Diagnostic Laboratory on the campus.
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`The purpose of these letters was to request that Drs. Haig Kazazian and Arupa Ganguly
`
`cease their commercial diagnostic testing. Myriad has never requested Drs. Kazazian and
`
`Ganguly, or anyone else, to not conduct research.
`
`20.
`
`Plaintiffs Haig Kazazian and Arupa Ganguly at the Genetic Diagnostic
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`Laboratory of the University of Pennsylvania were very quick in rushing to commercially
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`exploit the fruits of the hard-earned discoveries by Myriad and its collaborators. The
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`commercial nature of their BRCA testing services in the 1990s has been admitted by
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`PlaintiffKazazian. See e.g., D. Ganguly ,-r 4; D. Kazazian, ,-r,-r 3, 4, 8 and 10 ("At the time
`
`we were forced to stop offering BRCA genetic services, we were charging patients less
`
`than Myriad was charging.") (emphasis added). As Dr. Kazazian stated, "[t]hrough the
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`Genetic Diagnostic Laboratory, Dr. Ganguly and I provide state-of-the-art DNA-based
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`diagnostic testing for a variety of genetic conditions and diseases, as well as prenatal and
`
`predictive testing and genetic counseling services." D. Kazazian, ,-r 3 (emphasis added).
`
`The commercial nature of the lab is also confirmed by the information on its website. 18
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`For example, billing (CPT) codes are associated with every genetic test the lab offers.
`
`18 See Penn Medicine: The Genetic Diagnostic Laboratory, http://www.med.upenn.edu/gdl/ (last visited
`December 8, 2009).
`
`10
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`GeneDX 1014, pg. 10
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`Case 1:09-cv-04515-RWS Document 158 Filed 12/23/09 Page 11 of 33
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`For any testing by their lab, "[p ]ayment is required with sample submission. Patients
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`may choose to pay for their testing on a major credit card or submit a money order or
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`personal check payable to the Genetic Diagnostic Laboratory." 19 See id.; see also Exhibit
`
`5.
`
`21.
`
`The BRCA testing by Dr. Ganguly offered to the Cancer Genetics Network
`
`Project in 1998-1999 was also commercial in nature. D. Ganguly~~ 12 & 13. The
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`principal involvement by Dr. Ganguly in the Project was conducting DNA testing on the
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`BRCAJ and BRCA2 genes for fees. See id. Dr. Ganguly's lab was acting as a central
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`core lab for researchers much like other commercial core labs. In a meeting in late 1999
`
`at the National Cancer Institute ("NCI") with Dr. Kazazian and Dr. Richard Klausner, the
`
`then NCI director, Dr. Klausner clearly told Dr. Kazazian that the BRCA testing Drs.
`
`Kazazian and Ganguly were conducting was clearly commercial and did not qualify as
`
`research.
`
`22. Moreover, during a personal meeting with Piaintiff Dr. Haig Kazazian
`
`sometime between 1999 and 2000, I told him that he was free to do academic research on
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`the BRCAJ and BRCA2 genes including sequencing the genes and detecting mutations in
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`the genes.
`
`23.
`
`There is simply no evidence that Myriad has stopped or deterred any
`
`scientists from conducting research.
`
`II. PATENTS HAVE PROMOTED PATIENT ACCESS TO BRCA TESTING
`
`24.
`
`I believe broad "patient access" to a genetic test requires that (1) there be
`
`significant awareness and understanding of the test by patients and their healthcare
`
`t9 Id.
`
`11
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`GeneDX 1014, pg. 11
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`Case 1:09-cv-04515-RWS Document 158 Filed 12/23/09 Page 12 of 33
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`providers, and as a result, there is a desire for the test by those patients who may benefit
`
`from the test, (2) the test be of high quality and readily available when patients need it
`
`and test results are obtained in a timely manner, and (3) the test be affordable to most
`
`patients.
`
`25.
`
`To date, Myriad has performed over 400,000 BRACAnalysis® tests for
`
`BRCA mutations. We receive tests from all 50 states. Over 40,000 healthcare providers
`
`have ordered and used the test. Presently, test results are typically available within two
`
`weeks. More than 90% of the BRACAnalysis® tests ordered by healthcare providers are
`
`covered by insurance, and the average reimbursement rate is over 90% of the cost of the
`
`test. There are more than 2,600 insurance payors who reimburse for the BRACAnalysis ®
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`test. There are more than 80,000 insurance plans that cover the BRACAnalysis ®test.
`
`This undeniable "patient access" is the very result of Myriad's enormous investment in
`
`research, development, insurance coverage, and more importantly in raising patient and
`
`physician awareness and understanding of the test. Myriad wouid not have made the
`
`investment of more than 200 million dollars in raising patient and physician awareness
`
`alone without the protection provided by the exact patents the Plaintiffs are challenging.
`
`Myriad's story stands as a clear example of societal benefit due to patent protection. I am
`
`not aware of any diagnostic or pharmaceutical company that has made, or would be
`
`willing to make, this enormous investment without the benefit of a limited period of
`
`exclusivity engendered by patent rights.
`
`The Awareness Barrier
`
`26. When Myriad launched the commercial BRACAnalysis® test in late 1990s
`
`to screen for mutations in the BRCAJ and BRCA2 genes, knowledge about the genes was
`
`12
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`GeneDX 1014, pg. 12
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`Case 1:09-cv-04515-RWS Document 158 Filed 12/23/09 Page 13 of 33
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`largely limited to genetic researchers in universities. Moreover, the greatest benefit of
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`the test is to find healthy carriers of BRCA mutations who have not developed cancer, so
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`that early surveillance and preventive measures can be offered to these individuals.
`
`Without a good understanding of the role that BRCA mutations play in hereditary breast
`
`and ovarian cancer and genetic testing, there is little motivation for healthy individuals to
`
`even seek advice on genetic testing or their risks for predisposition to hereditary cancer.
`
`27.
`
`To bring genetic testing, or the BRACAnalysis® test, to those patients who
`
`can benefit from it, Myriad had to invest significant time and money to raise the
`
`awareness and understanding of genetic testing to patients and their healthcare providers,
`
`and to educate and convince the insurance industry of the pharmacoeconomics of the test.
`
`For example, Myriad has established a 300-person sales force calling on oncologists and
`
`OBGYN doctors all over the country. Our sales representatives, genetic counselors and
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`medical specialists are well-trained and well-versed on our tests. They meet personally
`
`with physicians, nurses and genetic counselors, providing them with :research papers and
`
`educational materials, answering questions on our tests, and helping in testing logistics.
`
`Our large team of in-house genetic counselors and medical experts provide their expertise
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`to help healthcare providers understand BRCA mutations, the BRACAnalysis® test and
`
`hereditary breast and ovarian cancer. In addition, Myriad organizes hundreds of
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`educational meetings for physicians to learn about BRCA-testing and hereditary breast
`
`and ovarian cancer from thought leaders who share their experience with their peers
`
`("speakers programs"). For example, during the July- September, 2009 quarter alone,
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`Myriad organized more than 300 such speakers programs all over the country.
`
`13
`
`GeneDX 1014, pg. 13
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`

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`Case 1:09-cv-04515-RWS Document 158 Filed 12/23/09 Page 14 of 33
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`28.
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`Direct proactive approaches in patient education have been shown in
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`research studies to be especially important in getting the message across to healthy family
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`members of cancer patients about the benefit of undergoing BRCA mutation screening. 20
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`Significantly, we have invested millions of dollars in patient awareness promotions on
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`TV and other popular media to raise the awareness of hereditary breast and ovarian
`
`cancer and BRACAnalysis® testing. Such promotions introduce hereditary breast and
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`ovarian cancer and encourage people who may be at risk for hereditary cancer to speak to
`
`their healthcare providers about their personal and family history of cancer to determine
`
`if genetic testing is appropriate for them. Our patient and physician outreach has made
`
`BRCA mutation testing available even in more remote rural areas. Without patent
`
`exclusivity, Myriad would not have made these investments.
`
`29.
`
`Indeed, because of Myriad's efforts, we now routinely receive patient
`
`samples from everywhere in all 50 states. More than 40,000 physicians and genetic
`
`counselors h'!ve used the BRACAnalysis® test. Over 400,000 patients who meet testing
`
`criteria have been tested at Myriad for mutations in the BRCAJ and BRCA2 genes. To
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`say that Myriad's patent rights have limited patient access is simply ignoring the facts.
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`To the contrary, patient awareness and access to important genetic testing has been
`
`significantly enhanced as a result of the patent grants at issue in this case.
`
`30.
`
`The diagnostic labs run by the geneticists plaintiffs such as those by Drs.
`
`Kazazian and Ganguly (the Genetic Diagnostic Laboratory at the University of
`
`20 See e.g., Evans eta!., Comparison of Proactive and Usual Approaches to Offering Predictive Testing for
`BRCAl/2 Mutations in Unaffected Relatives, CLIN. GENET., 75:124-32 (2009); see also Suthers et al.,
`Letting the Family Know: Balancing Ethics and Effectiveness When NotifYing Relatives about Genetic
`Testing for A Family Disorder, J. MED. GENET., 43:665-670 (2006).
`
`14
`
`GeneDX 1014, pg. 14
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`

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`Case 1:09-cv-04515-RWS Document 158 Filed 12/23/09 Page 15 of 33
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`Pennsylvania), Dr. Harry Ostrer (the Genetic Lab at NYU Langone Medical Center) and
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`Drs. David Ledbetter and Stephen Warren (at Emory Genetics Laboratory) are all within
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`major universities typically serving only patients within the major teaching hospitals
`
`affiliated with their respective universities. None of them would have been able to make
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`the substantial capital investment to do what Myriad has done in raising awareness and
`
`understanding of BRCA testing and reaching individuals who need these test services
`
`most, even in rural communities.
`
`The Cost Barrier
`
`31.
`
`Insurance reimbursement is a major barrier for patient access to any
`
`medical product. Myriad has invested significantly in building a strong marketing
`
`department including a team of experts specialized in working with insurance payors
`
`(private insurance companies, state-run Medicaids and Medicare) for reimbursement
`
`agreements to cover the cost of genetic testing. Today, Myriad has in place over 400
`
`contracts with private insurance payors that cover over 130 million lives in the US.
`
`Additional lives are covered under Medicaid and Medicare plans. In fact, between July
`
`2007 and now, more than 2,600 insurance payors have reimbursed the BRACAnalysis®
`
`test under more than 80,000 insurance plans.
`
`32.
`
`To reduce the out-of-pocket expense for patients, Myriad has set up a
`
`large Billing and Customer Service Department. Almost 150 individuals in this
`
`department interact daily with patients, their doctors, and their insurance companies to
`
`help patients work through the complexities of insurance coverage that could potentially
`
`prevent patients from receiving important testing services. Due to their efforts, over 90%
`
`of the tests Myriad performs are covered by insurance at over 90% of the test cost. As a
`
`15
`
`GeneDX 1014, pg. 15
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`

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`Case 1:09-cv-04515-RWS Document 158 Filed 12/23/09 Page 16 of 33
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`result, for the 90% of testing covered by insurance, the weighted average out-of-pocket
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`cost to each patient is less than $100.
`
`33.
`
`At Myriad, we also understand that there are patients in our country who
`
`do not have insurance and need help. Since 1996 when BRACAnalysis® was launched,
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`Myriad has had a financial assistance program directly providing free testing to low-
`
`income, uninsured patients. Just in the last four years, more than 3,000 patients have
`
`received free BRCA testing under this program (about 55 tests a month). In addition,
`
`Myriad also makes free testing available to needy patients through independent non-
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`profit organizations such as the Cancer Resource Foundation ("CRF") in Massachusetts.
`
`See http://www.breastcancerma.org/helping-hand/#genetic. In fact, through the CRF,
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`MassHealth patients such as Plaintiff Ceriani may receive BRACAnalysis® testing at no
`
`charge.
`
`34.
`
`Plaintiffs also alleged that the cost of the BRACAnalysis® testis too high
`
`because of patent exclusivity. However, the HHS Secretary's Advisory Committee on
`
`Genetics, Health, and Society ("SACGHS") in March 2009 released a Public
`
`Consultation Draft Report on Gene Patents and Licensing Practices and Their Impact on
`
`Patient Access to Genetic Tests. This Draft Report clearly stated: "One surprising
`
`finding from the case studies was that the per-unit price of the full-sequence BRCA test,
`
`which often is cited as being priced very high, was actually quite comparable to the price
`
`of other full-sequence tests done by polymerase chain reaction (PCR), at both nonprofit
`
`and for-profit testing laboratories."21
`
`21 SECRETARY'S ADVISORY COMMITTEE ON GENETICS, HEALTH, AND SOCIETY (SACGHS), PUBLIC
`CONSULTATION DRAFT REPORT ON GENE PATENTS AND LICENSING PRACTICES AND THEIR IMPACT ON
`PATIENT ACCESS TO GENETIC TESTS 114 (2009),
`
`16
`
`GeneDX 1014, pg. 16
`
`

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`Case 1:09-cv-04515-RWS Document 158 Filed 12/23/09 Page 17 of 33
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`35.
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`In fact, the relative price ofBRACAnalysis® is actually lower than the
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`gene sequencing-based genetic tests offered by those diagnostic labs run by the geneticist
`
`plaintiffs Kazazi