Case 1:20-cv-00038-CFC-CJB Document 1 Filed 01/13/20 Page 1 of 12 PageID #: 1
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`IN THE UNITED STATES DISTRICT COURT
`FOR THE DISTRICT OF DELAWARE
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`Plaintiff,
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`Defendant.
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`C.A. No. ___________
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`JURY TRIAL DEMANDED
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`NATERA, INC.,
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`CAREDX, INC.,
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`v.
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`Natera, Inc. (“Natera”) submits this Complaint against CareDx, Inc. (“CareDx”). Natera
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`COMPLAINT
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`hereby alleges as follows:
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`NATURE OF THE ACTION
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`1.
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`Natera brings this claim for patent infringement to compel CareDx to stop
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`infringing Natera’s patent and to compensate Natera for CareDx’s blatant infringement of
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`Natera’s patented technology.
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`2.
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`Founded in 2004, Natera (f.k.a Gene Security Network) is a pioneering genetics
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`and bioinformatics company with industry-leading diagnostics products. Natera is dedicated to
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`improving disease management for reproductive health, oncology, and organ transplantation. For
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`well over a decade, Natera has been researching, developing, and commercializing non-invasive
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`methods for analyzing DNA in order to help patients and doctors manage diseases.
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`These ongoing efforts have given rise to a number of novel and proprietary genetic testing
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`services to assist with life-saving health management.
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`3.
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`Natera’s pioneering and ongoing innovation is especially evident in the area of
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`cell-free DNA (“cfDNA”)-based testing. In the cfDNA field, Natera has developed unique and
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`highly optimized cfDNA-based diagnostic methods that can be used to non-invasively test for a
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`range of conditions. Natera developed an industry-leading cfDNA test, Panorama, which
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`showcases its mastery of cfDNA in the field of non-invasive prenatal diagnostics. It is
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`considered the industry leading test in this space, with over two million tests performed
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`commercially, and with more than twenty-six peer-reviewed publications. Natera has also
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`applied its cfDNA platform to the challenge of assessing organ transplant rejection. Natera’s
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`cfDNA testing methods are simpler and less invasive than traditional biopsy methods used to
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`evaluate transplant health, and also are more sensitive and specific, and less variable, than
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`current assessment tools—including biomarkers such as serum creatine—across all types of
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`kidney transplant rejection. Natera has developed its cfDNA technology for approval in the
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`clinical setting in order to provide patients with tools for early, clinically meaningful rejection
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`assessment. As such, Natera was awarded approval for coverage by Medicare.
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`4.
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`Natera’s cfDNA platform is the product of well over a decade of hard work and
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`investment of, on average, more than fifty million dollars per year in research and development.
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`Natera has expended substantial resources researching and developing its technologies and
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`establishing its reputation among physicians, insurers, and regulators as a company committed to
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`sound science and consistently accurate, reliable results. This research, and the resulting
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`technological innovations therefrom, are protected by a substantial patent portfolio, with over
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`200 patents issued or pending worldwide.
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`5.
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`Among these patented inventions is U.S. Patent No. 10,526,658 (the “’658
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`patent”), which CareDx infringes. In its efforts to improve upon the standard of care in the
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`transplant space, Natera has leveraged its own technologies such as the inventions disclosed and
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`claimed in the ’658 patent. By contrast, CareDx has used Natera’s patented cfDNA technology
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`without permission and in violation of the patent laws, while asserting only the patents of others
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`2
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`(e.g., Stanford) to create the false impression that it is a true innovator. CareDx must be held
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`accountable for its infringement.
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`6.
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`Natera is the legal owner by assignment of the ’658 patent, which was duly and
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`legally issued by the United States Patent and Trademark Office (“USPTO”) on January 7, 2020.
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`7.
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`Natera seeks monetary damages and injunctive relief to address ongoing
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`infringement by CareDx of its valuable patent.
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`THE PARTIES
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`8.
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`Natera is a Delaware corporation with its principal place of business at
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`201 Industrial Road, Suite 410, San Carlos, California 94070.
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`9.
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`CareDx is a Delaware corporation with its principal place of business at
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`3260 Bayshore Boulevard, Brisbane, California 94005.
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`JURISDICTION AND VENUE
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`10.
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`This is a civil action for patent infringement arising under the patent laws of the
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`United States, 35 U.S.C. §§ 1 et seq.
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`11.
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`This Court has subject matter jurisdiction over the matters asserted herein under
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`28 U.S.C. §§ 1331 and 1338(a).
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`12.
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`CareDx is subject to this Court’s personal jurisdiction at least because CareDx is a
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`Delaware corporation, and because CareDx filed its own actions against Natera, Case Nos. 19-
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`cv-00567-CFC-CJB and 19-cv-00662-CFC-CJB, in this District.
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`13.
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`In addition, CareDx is subject to this Court’s personal jurisdiction because, on
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`information and belief, CareDx, directly or indirectly, uses, offers for sale, and/or sells AlloSure
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`throughout the United States and within this District. CareDx has infringed and continues to
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`infringe Natera’s patent in this District by, among other things, engaging in infringing conduct
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`within and directed at or from this District and purposely and voluntarily placing its infringing
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`3
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`

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`product, AlloSure, into the stream of commerce with the expectation that the infringing product
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`will be used in this District.
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`14.
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`Venue is proper in this District pursuant to 28 U.S.C. §§ 1391 and 1400(b). As
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`discussed above, CareDx is incorporated in this District and thus resides in this District.
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`FACTUAL BACKGROUND
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`Natera’s History of Innovation
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`15.
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`Since 2004, Natera has been a global leader in genetic testing, diagnostics, and
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`DNA testing, including cfDNA testing. Natera’s mission is to improve the management of
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`disease worldwide and focuses on reproductive health, oncology, and organ transplantation. To
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`improve the management of these conditions, Natera has developed novel technologies to make
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`significant and accurate clinical assessments from the miniscule amounts of cfDNA present in a
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`single blood sample. These
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`technologies
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`include methods
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`to manipulate cfDNA
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`in
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`unconventional ways in order to capture information about genetic variations (“polymorphisms”)
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`in cfDNA and usefully transform that information for noninvasive testing. Natera develops and
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`commercializes its own innovative, non-traditional methods for manipulating and analyzing
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`cfDNA, and offers a host of proprietary cfDNA genetic testing services to the public to assist
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`patients and doctors to evaluate and track critical health concerns.
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`16.
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`Since its founding, Natera has researched, developed, and released ten molecular
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`tests with applications in prenatal diagnostics, cancer, and organ transplants, many of which are
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`available through major health plans, or covered by Medicare or Medicaid, and therefore
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`available to most patients in need of those tests. Natera’s tests have helped more than two
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`million individuals to date. Natera’s robust laboratory now processes tens of thousands of tests
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`per month from the United States and internationally, improving the ability of physicians to
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`monitor and manage crucial health issues and patients to prosper around the world.
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`4
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`17.
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`Building on these innovations, in 2019 Natera launched its patented next-
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`generation cfDNA diagnostic test for evaluating organ transplant health called “Prospera.”
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`Prospera is designed to be the most precise medical testing regime for early, clinically
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`meaningful transplant rejection assessment. Prospera assesses the risk of transplant rejection with
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`greater precision than the existing standard of care. Earlier tools for diagnosing organ transplant
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`rejection are either invasive or inaccurate. Prospera was created to help physicians improve
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`transplant survival by enabling them to optimally suppress immune-system-mediated rejection in
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`transplant recipients while avoiding unnecessary and invasive biopsies of the transplanted organ
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`itself.
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`18.
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`Prospera has been clinically and analytically validated for performance over all
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`donor types, rejection types, and clinical presentations. Prospera also is the first diagnostic test
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`with high sensitivity to both T-cell mediated and antibody mediated rejection. Prospera’s unique
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`ability to identify T-cell mediated rejection (“TCMR”) gives a more comprehensive view of a
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`patient’s rejection status. Prospera also is the first transplant test to publish the detection of
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`subclinical rejection, which occurs in 20-25% of patients in the first two years post-
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`transplant, and is considered a major driver of transplant failure.
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`19.
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`Prospera’s validation led Medicare to issue a draft Local Coverage Determination
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`(“LCD”) for Prospera in March 2019. In its draft LCD, Medicare determined that “[t]he evidence
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`is sufficient to support that Prospera provides a non-invasive assessment tool to assess for the
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`presence of active allograft rejection.” Furthermore, the LCD established that the “evidence also
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`supports that Prospera identifies both ABMR [antibody-mediated rejection] and TCMR [T-cell
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`mediated rejection], and it is validated to detect subclinical AR [active rejection].” The LCD
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`was finalized after receiving overwhelming public support, with the vast majority of public
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`5
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`comments being positive. Natera received nearly four times as many supportive letters than not.
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`In fact, the only three letters submitted which did not support the coverage were submitted either
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`by CareDx itself, by self-identified paid advocates of CareDx or, on information and belief, by
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`known CareDx advisors—all
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`in an attempt by CareDx
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`to
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`interfere with Natera’s
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`commercialization efforts.
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`20.
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`Natera’s history of and dedication to innovation in the analysis and testing of
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`cfDNA has resulted in a world-class patent portfolio, with over 86 patents issued to date. Natera
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`has well over 100 additional patent applications currently under review before the United States
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`Patent & Trademark Office (“USPTO”) and other patent offices around the world.
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`CareDx
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`21.
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`CareDx is a molecular diagnostics company that develops and commercializes
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`testing products for transplant recipients.
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`22.
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`23.
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`CareDx markets and sells its own transplant diagnostic test, called “AlloSure.”
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`On information and belief, AlloSure infringes the ’658 patent. The ’658 patent
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`covers an innovative, non-traditional method for manipulating and measuring DNA from a first
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`individual in a biological sample of a second individual. As set forth below, CareDx’s infringing
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`product, AlloSure, incorporates or uses technology that is protected by the ’658 patent owned by
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`Natera. CareDx has used Natera’s patented technology without payment or permission.
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`The ’658 Patent
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`24.
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`The ’658 patent, issued on January 7, 2020, is titled “Methods for Simultaneous
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`Amplification of Target Loci.” Joshua Babiarz, Tudor Pompiliu Constantin, Lane A. Eubank,
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`George Gemelos, Matthew Micah Hill, Huseyin Eser Kirkizlar, Matthew Rabinowitz, Onur
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`Sakarya, Styrmir Sigurjonsson, and Bernhard Zimmerman are the named inventors, and they
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`6
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`invented this technology as part of Natera’s innovative research team. Natera is the original and
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`current owner by assignment of the ’658 patent. A true and correct copy of the ’658 patent is
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`attached hereto as Exhibit A.
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`25.
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`Claim 1 of the ’658 patent recites:
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`1. A method for measuring an amount of DNA from a first individual in a biological
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`sample of a second individual, comprising:
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`pre-amplifying at least 50 polymorphic loci from cell-free DNA of mixed origin
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`in a single reaction volume to obtain pre-amplified DNA, wherein the cell-
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`free DNA is extracted from the biological sample and comprises DNA
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`from the first individual and DNA from the second individual, wherein
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`neither the first individual nor the second individual is a fetus;
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`dividing the pre-amplified DNA into multiple aliquots; amplifying subpools of the
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`polymorphic loci in parallel in individual reaction volumes to obtain
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`amplified DNA, wherein each reaction volume comprises at least one
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`aliquot of the pre-amplified DNA; and pooling the amplified DNA into
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`one pool;
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`sequencing the amplified DNA by high-throughput sequencing and measuring an
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`amount of each allele at the polymorphic loci; and
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`determining the amount of the DNA from the first individual in the biological
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`sample using the amount of each allele at the polymorphic loci.
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`26.
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`The claims of the ’658 patent are not directed to a natural law or natural
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`phenomenon. Rather, they are directed to measuring DNA in a sample using synthetic pieces of
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`DNA, including amplification products, which are produced using synthetic tools such as
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`7
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`primers, to provide a novel and innovative solution to problems peculiar to the particular
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`problem of amplifying and measuring small amounts of DNA from one individual or organism in
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`a biological sample of another individual or organism. The ’658 patent claims are directed to
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`specific, unconventional, non-routine methods for overcoming previously unresolved problems
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`in this area. Attached hereto as Exhibit F is the Declaration of Professor John Quackenbush,
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`Ph.D., which is incorporated here by reference, who further details the technological background
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`of the ’658 patent and documents its inventive nature, including its incorporation of an inventive
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`concept.
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`CareDx’s Infringing Acts
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`27.
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`The allegations provided below are exemplary and without prejudice to Natera’s
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`infringement contentions. In providing these allegations, Natera does not convey or imply any
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`particular claim constructions or the precise scope of the claims. Natera’s claim construction
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`contentions regarding the meaning and scope of the claim terms will be provided under the
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`Court’s scheduling order and local rules.
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`28.
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`The infringing products include, but are not limited to, AlloSure, CareDx’s kidney
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`transplant diagnostic test, and any other infringing method, product, device, or test developed by
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`CareDx.
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`29.
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`As provided in more detail below, each element of at least one claim of the ’658
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`patent is literally present in AlloSure or is literally practiced by the processes through which
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`AlloSure is practiced. To the extent that any element is not literally present or practiced, each
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`such element is present or practiced under the doctrine of equivalents.
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`30.
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`On information and belief, CareDx released its AlloSure product for kidney
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`transplant recipients to the public in 2017.
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`8
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`31.
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`Prior to that release, on November 6, 2016, CareDx—through Grskovic, et al.—
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`published a paper in the Journal of Molecular Diagnostics, titled Validation of a Clinical-Grade
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`Assay to Measure Donor-Derived Cell-Free DNA in Solid Organ Transplant Recipients, Vol. 18,
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`No. 6, pp. 890-902, attached hereto as Exhibit B. As indicated by CareDx’s AlloSure website
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`under Sample Preparation (http://www.allosure.com/sample-preparation/), this paper describes
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`CareDx’s AlloSure test and methodology. See Exhibit C at 1 (Sample Preparation) (“The test
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`design, development, and validation are described in Grskovic et al., J Mol Diagn, 2016.”).
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`32.
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`Performance of CareDx’s AlloSure test, and all variants thereof, infringe at least
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`one claim of the ’658 patent in the following way. Prospera measures cfDNA from a transplant
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`donor in a biological sample of a transplant recipient. This is based on targeted amplification of
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`266 single nucleotide polymorphisms (“SNPs”) in cfDNA extracted from the transplant
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`recipient’s blood. The 266 SNPs in the cfDNA are preamplified in a single multiplex reaction.
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`The preamplified material is divided into multiple aliquots and further amplified using 48 limited
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`complexity multiplexes with 1 to 11 targets per reaction. Index sequences and Illumina
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`sequencing adapters are added to each sample DNA by polymerase chain reaction (“PCR”), and
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`up to 16 amplified samples are pooled in equimolar amounts, and then sequenced with high-
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`throughput sequencing on an Illumina Mi-Seq. The sequencing data are then used to measure the
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`amount of each allele at the polymorphic loci to determine the amount of donor-derived cfDNA
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`in the sample.
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`33.
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`As an example, attached hereto as Exhibit D is a preliminary and exemplary claim
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`chart detailing CareDx’s infringement of the ’658 patent. Exhibit D is not intended to limit
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`Natera’s right to modify this chart or any other claim chart or allege that other activities of
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`CareDx infringe the identified claims or any other claims of the ’658 patent or any other patents.
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`9
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`34.
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`CareDx has thus made extensive use of Natera’s patented technology, including
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`the technology described and claimed in the ’658 patent. Natera has no choice but to defend its
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`proprietary and patented technology. Natera thus requests that this Court award it damages
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`sufficient to compensate for CareDx’s infringement of the ’658 patent, find this case exceptional
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`and award Natera its attorneys’ fees and costs, and grant an injunction against CareDx to prevent
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`ongoing infringement of the ’658 patent.
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`COUNT I: INFRINGEMENT OF U.S. PATENT NO. 10,526,658
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`35.
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`Natera incorporates by reference and re-alleges the foregoing paragraphs as if
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`fully set forth herein.
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`36.
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`On information and belief, CareDx has infringed and continues to infringe
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`the ’658 patent pursuant to 35 U.S.C. § 271(a), literally or under the doctrine of equivalents, by
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`performing within the United States without authority the AlloSure test. As an example, attached
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`as Exhibit D is a preliminary and exemplary claim chart detailing CareDx’s infringement of
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`the ’658 patent. This chart is not intended to limit Natera’s right to modify the chart or allege that
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`other activities of CareDx infringe the identified claims or any other claims of the ’658 patent or
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`any other patents.
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`37.
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`Exhibit D is hereby incorporated by reference in its entirety. Each claim element
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`in Exhibit D that is mapped to the AlloSure test is an allegation within the meaning of the
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`Federal Rules of Civil Procedure and therefore a response to each allegation is required.
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`PRAYER FOR RELIEF
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`WHEREFORE, Natera respectfully requests the following relief:
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`1.
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`A judgment that CareDx has infringed the ’658 patent literally or under the
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`doctrine of equivalents;
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`10
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`2.
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`An order preliminarily and permanently enjoining CareDx and its officers,
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`directors, agents, servants, affiliates, employees, divisions, branches, subsidiaries, parents, and
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`all others acting on behalf of or in active concert or participation therewith, from further
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`infringement of the ’658 patent;
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`3.
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`An award of damages sufficient to compensate Natera for CareDx’s infringement
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`under 35 U.S.C. § 284;
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`4.
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`A determination that this is an exceptional case under 35 U.S.C. § 285 and that
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`Natera be awarded attorneys’ fees;
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`5.
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`6.
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`7.
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`Costs and expenses in this action;
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`An award of prejudgment and post-judgment interest; and
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`Such other and further relief as the Court may deem just and proper.
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`DEMAND FOR JURY TRIAL
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`
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`Pursuant to Rule 38(b) of the Federal Rules of Civil Procedure, Natera respectfully
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`demands a trial by jury on all triable issues.
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`
`
`OF COUNSEL:
`
`Charles K. Verhoeven
`Andrew M. Holmes
`Carl G. Anderson
`QUINN EMANUEL URQUHART
` & SULLIVAN, LLP
`50 California Street, 22nd Floor
`San Francisco, CA 94111
`(415) 875-6600
`
`
`
`
`
`
`
`
`
`
`MORRIS, NICHOLS, ARSHT & TUNNELL LLP
`
`/s/ Jack B. Blumenfeld
`
`
`
`
`Jack B. Blumenfeld (#1014)
`Derek J. Fahnestock (#4705)
`Anthony D. Raucci (#5948)
`1201 North Market Street
`P.O. Box 1347
`Wilmington, DE 19899
`(302) 658-9200
`jblumenfeld@mnat.com
`dfahnestock@mnat.com
`araucci@mnat.com
`
`Attorneys for Plaintiff Natera, Inc.
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`11
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`Case 1:20-cv-00038-CFC-CJB Document 1 Filed 01/13/20 Page 12 of 12 PageID #: 12
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`
`
`Sandra Haberny, Ph.D.
`QUINN EMANUEL URQUHART
` & SULLIVAN, LLP
`865 South Figueroa Street, 10th Floor
`Los Angeles, CA 90017
`(213) 443-3000
`
`January 13, 2020
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`12
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