Case 2:21-cv-09011-RGK-GJS Document 168 Filed 05/02/22 Page 1 of 39 Page ID #:4987
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`
`David A. Sergenian (SBN 230174)
`SERGENIAN LAW
`2355 Westwood Blvd. #529
`Los Angeles, CA 90064
`(213) 435-2035
`david@sergenianlaw.com
`
`John M. Desmarais (SBN 320875)
`Gabrielle E. Higgins (SBN 163179)
`DESMARAIS LLP
`101 California Street
`San Francisco, CA 94111
`T: 415-573-1900 / F: 415-573-1901
`jdesmarais@desmaraisllp.com
`ghiggins@desmaraisllp.com
`
`Counsel for Plaintiff/Counterclaim-
`Defendant Ravgen, Inc.
`
`
`Kerri-Ann Limbeek (pro hac vice)
`Benjamin N. Luehrs (pro hac vice)
`DESMARAIS LLP
`230 Park Avenue
`New York, NY 10169
`T: 212-351-3400 / F: 212-351-3401
`klimbeek@desmaraisllp.com
`bluehrs@desmaraisllp.com
`
`Counsel for Plaintiff/Counterclaim-
`Defendant Ravgen, Inc.
`
`[Additional Counsel Listed on Signature
`Block]
`
`
`UNITED STATES DISTRICT COURT
`CENTRAL DISTRICT OF CALIFORNIA
`
`
`Ravgen, Inc.,
`
`
`Plaintiff,
`
`
`v.
`
`Quest Diagnostics Incorporated and
`Quest Diagnostics Nichols Institute,
`
`Defendants.
`
`
`Case No. 2:21-cv-09011-RGK-GJS
`
`FIRST AMENDED COMPLAINT
`FOR PATENT INFRINGEMENT
`
`
`JURY TRIAL DEMANDED
`
`
`
`Quest Diagnostics Incorporated,
`
`Counterclaimant,
`
`
`v.
`
`Ravgen, Inc.,
`
`Counterclaim-Defendant.
`
`FIRST AMENDED COMPLAINT FOR PATENT
`INFRINGEMENT
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`
`Case No. 2:21-cv-09011-RGK-GJS
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`Case 2:21-cv-09011-RGK-GJS Document 168 Filed 05/02/22 Page 2 of 39 Page ID #:4988
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`Plaintiff Ravgen, Inc. (“Ravgen”), for its First Amended Complaint against
`
`Defendants Quest Diagnostics Incorporated (“Quest”) and Quest Diagnostics Nichols
`Institute (“Quest Nichols”) (collectively, “Defendants”), hereby alleges as follows:
`NATURE OF THE ACTION
`1.
`This is a civil action for infringement of United States Patent Nos.
`7,727,720 (the “’720 Patent”) and 7,332,277 (the “’277 Patent”) (collectively the
`“Patents-in-Suit”), arising under the Patent Laws of the United States, 35 U.S.C.
`§§ 271 et seq.
`
`THE PARTIES
`2.
`Plaintiff Ravgen is a Delaware corporation with its principal place of
`business at 9241 Rumsey Rd., Columbia, MD 21045. Ravgen is a pioneering
`diagnostics company that focuses on non-invasive prenatal testing. Ravgen has spent
`millions of dollars researching and developing novel methods for the detection of cell-
`free DNA to replace conventional, invasive procedures. Ravgen’s innovative cell-free
`DNA technology has various applications, including non-invasive prenatal and other
`genetic testing. Those efforts have resulted in the issuance of several patents,
`including the Patents-in-Suit.
`3.
`Defendant Quest is a Delaware corporation with its principal place of
`business at 500 Plaza Drive, Secaucus, NJ 07094. (ECF No. 152 at ¶ 3 (Quest
`Answer); Ex. 48.) Quest is registered to do business in the state of California. (Ex.
`41.) Quest has appointed Corporation Service Company (d/b/a CSC – Lawyers
`Incorporating Service Company), located at 2710 Gateway Oaks Drive, Suite 150N,
`Sacramento, CA 95833, as its agent for service of process. (Ex. 48; Ex. 42.) Quest
`maintains several places of business in this District, including patient collection
`centers that offer diagnostic tests (e.g., the QNatal Advanced test), such as at 1300
`Avenida Vista Hermosa, Suite 160, San Clemente, CA 92673; and other offices, such
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`FIRST AMENDED COMPLAINT FOR PATENT
`INFRINGEMENT
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`as at 675 Camino De Los Mares, Suite 300, San Clemente, CA 92673. (See, e.g., Ex.
`43 (https://appointment.questdiagnostics.com/find-location/as-location-finder); Exs.
`50-51 (Dun & Bradstreet reports identifying the businesses at the addresses as Quest
`Diagnostics).)
`4.
`Defendant Quest Nichols is a Delaware corporation with its principal
`place of business at 33608 Ortega Highway, San Juan Capistrano, CA 92675. (ECF
`No. 152 at ¶ 48 (Quest Answer); Ex. 49.) Quest Nichols is. 4 registered to do business
`in the state of California. (Ex. 44). Quest has appointed Corporation Service
`Company (d/b/a CSC – Lawyers Incorporating Service Company), located at 2710
`gateway Oaks Drive, Suite 150N, Sacramento, CA 95833, as its agent for service of
`process. (Ex. 49; Ex. 42.)
`5.
`Quest and Quest Nichols each have employees at the San Juan
`Capistrano location above. (See, e.g., ECF No. 21 at 13 (Quest Motion to Transfer).)
`6.
`Defendants commercialize genetic tests using cell-free DNA, including a
`non-invasive prenatal diagnostic test for the determination of fetal chromosomal
`abnormalities marketed under the trade name “QNatal Advanced.” Defendants offer
`and market this test throughout the United States, at least through the website
`www.questdiagnostics.com. (See generally Ex. 12
`(https://www.questdiagnostics.com/home/patients/health-test-info/womens-
`health/prenatal/during-pregnancy/noninvasive/).)
`JURISDICTION AND VENUE
`7.
`Ravgen incorporates by reference paragraphs 1–6.
`8.
`This action arises under the patent laws of the United States, including 35
`U.S.C. §§ 271 et seq. The jurisdiction of this Court over the subject matter of this
`action is proper under 28 U.S.C. §§ 1331 and 1338(a).
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`FIRST AMENDED COMPLAINT FOR PATENT
`INFRINGEMENT
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`9.
`Venue is proper in this District pursuant to U.S.C. §§ 1391(b), (c), (d),
`and 1400(b) because Defendants have a permanent and continuous presence in, have
`committed acts of infringement in, and maintain regular and established places of
`businesses in, this District.
`10. By registering to conduct business in California and by having facilities
`where it regularly conducts business in this District, Defendants have a permanent and
`continuous presence and regular and established places of business in the Central
`District of California.
`11. Quest maintains regular and established places of business in this
`District. (See, e.g., ECF No. 152 at ¶ 48-49 (Quest Answer); ECF No. 21 at 13.) On
`information and belief, Quest holds out at least its patient collection centers that offer
`diagnostic tests, including at 1300 Avenida Vista Hermosa, Suite 160, San Clemente,
`CA 92673, as Quest’s own, including by displaying its name at these locations, listing
`these locations and directing patients to these locations on its website located at
`https://appointment.questdiagnostics.com/find-location/as-location-finder. (See Ex.
`43; Ex. 7 at 1 (Quest Diagnostics Incorporated’s Form 10-K for Fiscal Year 2019)
`(“We conduct business through . . . our laboratories, patient service centers, offices
`and other facilities around the United States . . . .”); id. at 38 (“We also maintain
`offices . . . and patient service centers at locations throughout the United States.”).)
`Further, Quest’s places of business in this District include other laboratories, such as
`at 33608 Ortega Highway, San Juan Capistrano, CA 92675. (See Ex. 45 (Dun &
`Bradstreet report identifying the business at this location as Quest Diagnostics Nichols
`Institute); Ex. 46 (Google street view photos of this location showing “Quest
`Diagnostics”)). On information and belief, employees of Quest carry out Quest’s
`business at places of business in this District. (See, e.g., ECF No. 21 at 13)
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`FIRST AMENDED COMPLAINT FOR PATENT
`INFRINGEMENT
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`12. Quest Nichols maintains regular and established places of business in this
`District, including a laboratory at 33608 Ortega Highway, San Juan Capistrano, CA
`92675. (See ECF No. 152 at ¶ 48-49 (Quest Answer); Ex. 44; Ex. 49.) On
`information and belief, Quest Nichols holds out these places of business as its own,
`including by displaying its name at this location, listing this location and directing
`patients to this location on its website located at
`https://www.questdiagnostics.com/locations/search.html/domestic (See Ex. 47.)
`13. Defendants offer for sale and sell cell-free DNA tests that employ
`methods claimed in the Patents-in-Suit, including the QNatal Advanced test,
`throughout the United States, including through its website, which is accessible in this
`District. (See, e.g., Ex. 15
`(https://www.questdiagnostics.com/home/physicians/testing-services/by-test-
`name/noninvasive/requisition/); Ex. 16 at 2
`(https://www.questdiagnostics.com/home/physicians/testing-services/by-test-
`name/noninvasive/faq/) (“How do I order QNatal Advanced? . . . contact your sales
`representative, email a genetic counselor at GENEINFO@QuestDiagnostics.com, or
`call 1.866.GENE.INFO (1.866.436.3463).”); Ex. 17
`(https://www.questdiagnostics.com/dms/Documents/Other/QNatal-
`Requisition/QNatal%20Requisition.pdf) (physician order form for QNatal
`Advanced).)
`14. Quest has committed acts of direct infringement in this judicial District.
`For example, on information and belief, Quest commits acts of infringement in this
`District by offering for sale and selling the performance of infringing methods at
`Quest’s patient collection centers, such as at 1300 Avenida Vista Hermosa, Suite 160,
`San Clemente, CA 92673. Specifically, as detailed further below, Quest offers for
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`FIRST AMENDED COMPLAINT FOR PATENT
`INFRINGEMENT
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`sale and sells the obligation to perform the steps of the patented methods by, for
`example, offering for sale and selling the QNatal Advanced test.
`15. Quest has also committed acts of direct infringement in this judicial
`District itself and/or through its wholly owned subsidiary Quest Nichols. For
`example, on information and belief, Quest, itself and/or through its wholly owned
`subsidiary Quest Nichols, which acts as an agent and alter ego of Quest and is
`completely controlled and dominated by Quest, performs infringing methods in this
`District by using the QNatal Advanced tests, including processing the results of those
`tests, in offices and laboratories at 33608 Ortega Highway, San Juan Capistrano, CA
`92675.
`16. Quest Nichols has committed acts of direct infringement in this judicial
`District. For example, on information and belief, Quest Nichols performs infringing
`methods in this District by using the QNatal Advanced tests, including processing the
`results of those tests, in offices and laboratories at 33608 Ortega Highway, San Juan
`Capistrano, CA 92675. (ECF No. 152 at ¶ 48-49 (Quest Answer).)
`17. Venue is also proper because Quest Nichols is a wholly-owned
`subsidiary of Quest, operates as an agent and alter-ego of Quest, and is completely
`controlled and dominated by Quest. Quest directs and is involved in the activities of
`Quest Nichols, and they operate as a single company. As the corporate parent of
`Quest Nichols, Quest has participated in the commission of patent infringement in this
`judicial District, including by making, using, offering for sale, and/or selling the
`QNatal Advanced tests in this District and elsewhere that led to foreseeable harm and
`injury to Ravgen. Quest’s SEC filings confirm that at all relevant times, Quest owned
`and owns 100% of Quest Nichols, and that Quest has the right and the ability to direct
`and control the activities of Quest Nichols. (E.g., Ex. 7 at Exhibit 21.1 (“Subsidiaries,
`Joint Ventures and Affiliates” on Form 10-K).) Further, Quest directs and is involved
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`FIRST AMENDED COMPLAINT FOR PATENT
`INFRINGEMENT
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`in the activities of Quest Nichols, and they operate as a single company. (Ex. 7 at 11
`(“We maintain a nationwide network of laboratories, including advanced laboratories
`(such as our world-renowned Quest Diagnostics Nichols Institute) . . . .”).)
`Additionally, at least some members of the Quest “Management Team” work at Quest
`Nichols. For example, Jay G. Wohlgemuth, M.D. is Senior Vice President, R&D,
`Medical and Chief Medical Officer for Quest, and also works at Quest Nichols. (Ex.
`40 at 2 (https://ir.questdiagnostics.com/governance/management-team/default.aspx)
`(“Based in Quest Diagnostics Nichols Institute, in San Juan Capistrano, California,
`Dr. Wohlgemuth is responsible for Research & Development, Medical Affairs, and
`Medical/Lab Quality.”).) On information and belief, Dr. Wohlgemuth is an employee
`and/or officer of Quest, whose leadership position at Quest Nichols further enables
`Quest to exercise direction and control over the activities of its fully owned
`subsidiary, Quest Nichols.
`18. Quest is subject to this Court’s jurisdiction pursuant to due process
`and/or the California Long Arm Statute due at least to its substantial business in this
`State and judicial District, including at least regularly doing and soliciting business at
`the San Juan Capistrano facility identified above, and engaging in persistent conduct
`and/or deriving substantial revenue from goods and services provided to customers in
`the State of California, including in the Central District of California. For example,
`Quest conducts business in the District by at least offering for sale and selling
`products and services that comprise the performance of the claimed methods of the
`Patents-in-Suit, including the QNatal Advanced test, including through Quest’s
`websites, which are accessible in this District. In addition, Quest leases and operates
`patient collection centers in this District that sell, offer for sale, and support products
`and services that comprise the performance of the claimed methods of the Patents-in-
`Suit, including at least the QNatal Advanced test.
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`FIRST AMENDED COMPLAINT FOR PATENT
`INFRINGEMENT
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`19. This Court has personal jurisdiction over Quest due, inter alia, to its
`continuous presence in, and systematic contact with, this District and its registration in
`California. (See Ex. 41; Ex. 48.) Quest has established minimum contacts within the
`forum such that the exercise of jurisdiction over Quest will not offend traditional
`notions of fair play and substantial justice.
`20. Personal jurisdiction exists over Quest because Quest, directly and/or
`through subsidiaries or intermediaries, has committed and continues to commit acts of
`infringement in this District by, among other things, using products and/or services
`that infringe the Patents-in-Suit, which led to foreseeable harm and injury to Ravgen.
`21. Quest Nichols is subject to this Court’s jurisdiction pursuant to due
`process and/or the California Long Arm Statute due at least to its substantial business
`in this State and judicial District, including at least part of its infringing activities,
`regularly doing and soliciting business at its 33608 Ortega Highway, San Juan
`Capistrano, CA 92675, facilities, and engaging in persistent conduct and/or deriving
`substantial revenue from goods and services provided to customers in the State of
`California, including in the Central District of California. For example, Quest Nichols
`conducts business in the District by at least processing the QNatal Advanced tests in
`laboratories at 33608 Ortega Highway, San Juan Capistrano, CA 92675.
`22. This Court has personal jurisdiction over Quest Nichols due, inter alia, to
`its continuous presence in, and systematic contact with, this judicial District and its
`registration in California. Quest Nichols has established minimum contacts within the
`forum such that the exercise of jurisdiction over Quest Nichols will not offend
`traditional notions of fair play and substantial justice.
`23. Personal jurisdiction exists over Quest Nichols because Quest Nichols
`has committed and continues to commit acts of infringement in this judicial District
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`FIRST AMENDED COMPLAINT FOR PATENT
`INFRINGEMENT
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`by, among other things, using products and/or services that infringe the Patents-in-
`Suit, which led to foreseeable harm and injury to Ravgen.
`BACKGROUND OF THE INVENTION
`24. Dr. Ravinder S. Dhallan is the founder of Ravgen, Inc. and the inventor
`of several patents in the field of detection of genetic disorders, including chromosomal
`abnormalities and mutations. Ravgen’s mission is to provide state of the art genetic
`testing that will enrich the lives of its patients. For example, through the use of its
`novel techniques in non-invasive prenatal diagnostic testing, Ravgen gives patients the
`knowledge they need to prepare for their pregnancies and treat diseases at an early
`stage.
`25. Prior to founding Ravgen, Dr. Dhallan was a board-certified emergency
`room physician. During his time at medical school and his residency at Mass General
`(Harvard University School of Medicine), Dr. Dhallan and his wife suffered three
`miscarriages. At that time, the prenatal diagnostic testing procedures available
`included (a) non-invasive techniques with low sensitivity and specificity, and (b) tests
`with higher sensitivity and specificity that were highly invasive and therefore
`associated with a risk for loss of pregnancy. After discovering the limitations on the
`available techniques for prenatal testing, Dr. Dhallan made it his mission to invent an
`improved prenatal diagnostic exam—one that was both non-invasive and accurate. In
`September of 2000, Dr. Dhallan founded Ravgen (which stands for “Rapid Analysis
`of Variations in the GENome”) to pursue that goal.
`26. Prior to Ravgen’s inventions, scientists had recognized the need for a
`genetic testing technique that used “cell-free” or “free” fetal DNA circulating in
`maternal blood. A technique that relied on circulating free fetal DNA would require
`only a simple blood draw from the mother and would therefore be improvement over
`invasive diagnostic tests.
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`27. However, at that time, the use of free fetal DNA for detecting
`chromosomal abnormalities was limited by the low percentage of free fetal DNA that
`could be recovered from a sample of maternal blood using existing techniques. (See,
`e.g., Ex. 18 (Y.M. Dennis Lo et al., Presence of Fetal DNA in Maternal Plasma and
`Serum, 350 THE LANCET 768-75 (1997), https://doi.org/10.1016/S0140-
`6736(97)02174-0.) Dr. Dhallan recognized that a method that could increase the
`percentage of free fetal DNA relative to the free maternal DNA in a sample was
`necessary to the development of an accurate, non-invasive prenatal diagnostic test.
`28. After substantial research, Dr. Dhallan conceived that including an agent
`that impedes cell lysis (disruption of the cell membrane) if cells are present during
`sample collection, shipping, handling, and processing would permit the recovery of a
`larger percentage of cell-free fetal DNA (relative to the cell-free maternal DNA in a
`sample). Dr. Dhallan hypothesized that this new approach would decrease the amount
`of maternal cell lysis and therefore lower the amount of cell-free maternal DNA in the
`sample, thereby increasing the percentage of cell-free fetal DNA. He developed a
`novel method for processing cell-free fetal DNA that involved the addition of an agent
`that impedes cell lysis—for example, a membrane stabilizer, a cross-linker, and/or a
`cell lysis inhibitor—to maternal blood samples coupled with careful processing
`protocols. With that novel method, Dr. Dhallan was able to increase the relative
`percentage of cell-free fetal DNA in the processed sample.
`29. Having successfully increased the relative percentage of cell-free fetal
`DNA recovered, Dr. Dhallan next addressed the challenge of distinguishing between
`the cell-free maternal and cell-free fetal DNA in a sample in order to determine
`whether a chromosomal abnormality is present in the fetal DNA. Prior to Ravgen’s
`inventions, known methods for detecting fetal chromosomal abnormalities were time-
`consuming and burdensome. Many required amplification of the entire sequence of a
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`gene, or quantification of the total amount of a particular gene product in a sample.
`Dr. Dhallan developed an alternate method that greatly increased the efficiency of this
`process by taking advantage of the variation of base sequences among different
`individuals (including a mother and fetus) (“alleles”) at particular positions (“loci”) on
`chromosomes. The term “allele” refers to an alternate form of a gene, or a non-coding
`region of DNA that occurs at a particular loci on a chromosome. The alleles present
`at certain loci on chromosomes (including, for example, “single nucleotide
`polymorphisms” or “SNPs”) vary between different individuals. At such a locus, a
`fetus may therefore inherit an allele from its father that differs from the alleles present
`at that locus on its mother’s chromosome. Dr. Dhallan developed a novel method for
`quantifying the allelic ratio at such a locus (or loci) of interest in a sample comprising
`maternal and fetal cell-free DNA in order to detect whether a fetal chromosomal
`abnormality was present in the fetal DNA of the sample, without requiring physical
`separation of the fetal from the maternal cell-free DNA.
`30. Dr. Dhallan understood that his breakthroughs laid the foundation for the
`development of accurate non-invasive prenatal diagnostic tests. For example, he
`published a paper in the Journal of the American Medical Association (JAMA) in
`2004, explaining that “the methods described herein for increasing the percentage of
`cell-free fetal DNA provide a solid foundation for the development of a noninvasive
`prenatal diagnostic test.” (Ex. 19 at 1119 (R. Dhallan et al., Methods to Increase the
`Percentage of Free Fetal DNA Recovered from the Maternal Circulation, 291 JAMA
`1114–19 (2004), https://doi.org/10.1001/jama.291.9.1114).)
`31.
`JAMA also ran an editorial alongside Dr. Dhallan’s article in 2004,
`recognizing the significance of his inventions to applications in prenatal genetic
`diagnosis and cancer detection and surveillance:
`
`FIRST AMENDED COMPLAINT FOR PATENT
`INFRINGEMENT
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`10
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`Case No. 2:21-cv-09011-RGK-GJS
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`Case 2:21-cv-09011-RGK-GJS Document 168 Filed 05/02/22 Page 12 of 39 Page ID
`#:4998
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`In this issue of THE JOURNAL, the findings reported in the
`study by Dhallan and colleagues on enhancing recovery of
`cell-free DNA in maternal blood have major clinical
`implications. Developing a reliable, transportable
`technology for cell-free DNA analysis impacts 2 crucial
`areas—prenatal genetic diagnosis and cancer detection and
`surveillance. In prenatal genetic diagnosis, detecting a fetal
`abnormality without an invasive procedure (or with fewer
`invasive procedures) is a major advantage. Likewise in
`cancer surveillance (eg, in patients with leukemia),
`monitoring treatment without having to perform a bone
`marrow aspiration for karyotype also would be of great
`benefit.
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`* * *
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`With prospective studies focusing on clinical applications of
`these findings, profound clinical implications could emerge
`for prenatal diagnosis and cancer surveillance.
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`(Ex. 20 at 1135, 1137 (J.L. Simpson & F. Bischoff, Cell-Free Fetal DNA in Maternal
`Blood: Evolving Clinical Applications, 291 JAMA 1135–37 (2004),
`https://doi.org/10.1001/jama.291.9.1135).)
`32.
`In 2007, Dr. Dhallan published a second journal article in The Lancet that
`presented a study showcasing Ravgen’s ability to use its novel technology to detect
`Down’s syndrome using free fetal DNA in a maternal blood sample. (Ex. 21 (R.
`Dhallan et al., A Non-Invasive Test for Prenatal Diagnosis Based on Fetal DNA
`Present in Maternal Blood: A Preliminary Study, 369 THE LANCET 474–81 (2007),
`https://doi.org/10.1016/S0140-6736(07)60115-9).) Dr. Dhallan’s peers at The Lancet
`also recognized that his innovative test “opens a new era in prenatal screening.” (See
`Ex. 22 (A. Benachi & J.M. Costa, Non-Invasive Prenatal Diagnosis of Fetal
`Aneuploidies, 369 THE LANCET 440–42 (2007), https://doi.org/10.1016/S0140-
`6736(07)60116-0).)
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`FIRST AMENDED COMPLAINT FOR PATENT
`INFRINGEMENT
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`11
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`Case No. 2:21-cv-09011-RGK-GJS
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`Case 2:21-cv-09011-RGK-GJS Document 168 Filed 05/02/22 Page 13 of 39 Page ID
`#:4999
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`33. Dr. Dhallan’s publications received worldwide press coverage, from
`outlets such as CNN, BBC, and Washington Post. (See Ex. 23 (L. Palmer, A Better
`Prenatal Test?, CNN MONEY (Sept. 12, 2007),
`https://money.cnn.com/2007/09/07/smbusiness/amniocentesis
`.fsb/index.htm); Ex. 24 (Hope for Safe Prenatal Gene Test, BBC NEWS, Feb 2, 2007,
`http://news.bbc.co.uk/2/hi/health/6320273.stm); Ex. 25 (A. Gardner, Experimental
`Prenatal Test Helps Spot Birth Defects, WASH. POST (Feb. 2, 2007),
`https://www.washingtonpost.com/wp-
`dyn/content/article/2007/02/02/AR2007020200914.html).)
`34. The Patents-in-Suit resulted from Dr. Dhallan’s years-long research at
`Ravgen to develop these innovative new methods for detecting genetic disorders.
`PATENTS-IN-SUIT
`35. Ravgen incorporates by reference paragraphs 1–34.
`36. The ’277 Patent, entitled “Methods For Detection Of Genetic Disorders,”
`was duly and legally issued by the United States Patent and Trademark Office on
`February 19, 2008. The inventor of the patent is Ravinder S. Dhallan, and the patent
`is assigned to Ravgen. A copy of the ’277 Patent is attached hereto as Exhibit 1.
`37. Ravgen is the exclusive owner of all rights, title, and interest in the ’277
`Patent, and has the right to bring this suit to recover damages for any current or past
`infringement of the ’277 Patent. (See Ex. 3.)
`38. The ’720 Patent, entitled “Methods For Detection Of Genetic Disorders,”
`was duly and legally issued by the United States Patent and Trademark Office on June
`1, 2010. The inventor of the patent is Ravinder S. Dhallan, and the patent is assigned
`to Ravgen. A copy of the ’720 Patent is attached hereto as Exhibit 2.
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`FIRST AMENDED COMPLAINT FOR PATENT
`INFRINGEMENT
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`12
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`Case No. 2:21-cv-09011-RGK-GJS
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`Case 2:21-cv-09011-RGK-GJS Document 168 Filed 05/02/22 Page 14 of 39 Page ID
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`39. Ravgen is the exclusive owner of all rights, title, and interest in the ’720
`Patent, and has the right to bring this suit to recover damages for any current or past
`infringement of the ’720 Patent. (See Ex. 4.)
`40. The ’277 Patent is directed to, among other things, novel methods used in
`the detection of genetic disorders. For example, claim 81 of the ’277 Patent recites:
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`A method for preparing a sample for analysis comprising
`isolating free fetal nucleic acid from a the sample, wherein
`said sample comprises an agent that inhibits lysis of cells, if
`cells are present, and wherein said agent is selected from the
`group consisting of membrane stabilizer, cross-linker, and
`cell lysis inhibitor.
`
`41. The ’720 Patent is directed to novel methods for detecting a free nucleic
`acid in a sample. For example, claim 1 of the ’720 Patent recites:
`
`A method for detecting a free nucleic acid, wherein said
`method comprises: (a) isolating free nucleic acid from a
`non-cellular fraction of a sample, wherein said sample
`comprises an agent that impedes cell lysis, if cells are
`present, and wherein said agent is selected from the group
`consisting of membrane stabilizer, cross-linker, and cell
`lysis inhibitor; and (b) detecting the presence or absence of
`the free nucleic acid.
`42. The Patents-in-Suit are directed to unconventional, non-routine
`techniques for preparing and analyzing extracellular circulatory DNA, including for
`the detection of genetic disorders. The Patents-in-Suit explain that, inter alia, the
`inventions claimed therein overcame problems in the field—for example, that the low
`percentage of fetal DNA in maternal plasma makes using the DNA for genotyping the
`fetus difficult—with a novel and innovative solution—the addition of cell lysis
`inhibitors, cell membrane stabilizers or cross-linkers to the maternal blood sample,
`which increase the percentage of cell-free DNA available for detection and analysis:
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`FIRST AMENDED COMPLAINT FOR PATENT
`INFRINGEMENT
`
`13
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`Case No. 2:21-cv-09011-RGK-GJS
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`Case 2:21-cv-09011-RGK-GJS Document 168 Filed 05/02/22 Page 15 of 39 Page ID
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`The percentage of fetal DNA in maternal plasma is between
`0.39-11.9% (Pertl, and Bianchi, Obstetrics and Gynecology
`98: 483-490 (2001)). The majority of the DNA in the
`plasma sample is maternal, which makes using the DNA
`for genotyping the fetus difficult. However, methods that
`increase the percentage of fetal DNA in the maternal plasma
`allow the sequence of the fetal DNA to be determined, and
`allow for the detection of genetic disorders including
`mutations, insertions, deletions, and chromosomal
`abnormalities. The addition of cell lysis inhibitors, cell
`membrane stabilizers or cross-linkers to the maternal
`blood sample can increase the relative percentage of fetal
`DNA. While lysis of both maternal and fetal cells is
`inhibited, the vast majority of cells are maternal, and thus by
`reducing the lysis of maternal cells, there is a relative
`increase in the percentage of free fetal DNA.
`
`(Ex. 1 (’277 Patent) at 32:24–39; Ex. 2 (’720 Patent) at 33:31–46 (emphases added).)
`43. The Patents-in-Suit teach that the benefit of Dr. Dhallan’s discovery, an
`increase in the relative percentage of cell-free DNA, is realized by performance of the
`claimed method, including through the inclusion of an agent that inhibits the lysis of
`the cells in a sample:
`An overall increase in fetal DNA was achieved by reducing
`the maternal cell lysis, and thus, reducing the amount of
`maternal DNA present in the sample. In this example,
`formaldehyde was used to prevent lysis of the cells, however
`any agent that prevents the lysis of cells or increases the
`structural integrity of the cells can be used. The increase in
`fetal DNA in the maternal plasma allows the sequence of the
`fetal DNA to be determined, and provides for the rapid
`detection of abnormal DNA sequences or chromosomal
`abnormalities including but not limited to point mutation,
`reading frame shift, transition, transversion, addition,
`insertion, deletion, addition-deletion, frame-shift, missense,
`reverse