Case 2:17-cv-00140-RWS-RSP Document 26-6 Filed 07/13/17 Page 1 of 13 PageID #: 392
`Case 2:17-cv—00140-RWS—RSP Document 26-6 Filed 07/13/17 Page 1 of 13 PageID #: 392
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`EXHIBIT F
`EXHIBIT F
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`2013 WL 7117636 (N.D.Cal.) (Trial Pleading)
`United States District Court, N.D. California.
`San Francisco Division
`
`GENETIC TECHNOLOGIES LIMITED, an Australian corporation, Plaintiff,
`v.
`AGILENT TECHNOLOGIES, INC., a Delaware corporation, Defendant.
`
`No. 3:12-cv-01616-RS.
`December 5, 2013.
`
`Courtroom: 3
`
`Second Amended Complaint with Jury Demand
`
`Rodney B. Sorensen, Bar No. 196926, rbs@paynefears.com, Payne & Fears LLP, Attorneys at Law, One Embarcadero
`Center, Suite 2300, San Francisco, CA 94111, Telephone: (415) 398-7860, Facsimile: (415) 398-7863.
`
`Robert R. Brunelli (Admission Pro Hac Vice), rbrunelli@sheridanross.com, Benjamin B. Lieb (Admission Pro Hac
`Vice), blieb@sheridanross.com, Sheridan Ross P.C., 1560 Broadway, Suite 1200, Denver, CO 80202-5141, Telephone:
`(303) 863-9700, Facsimile: (303) 863-0223.
`
`Attorneys for Plaintiff, Genetic Technologies Limited.
`
`Judge: Hon. Richard Seeborg.
`
`Plaintiff Genetic Technologies Limited (“GTG”) files this First Amended Complaint against Defendant Agilent
`Technologies, Inc. (“Agilent”) alleging as follows:
`
`I. THE PARTIES
`
`1. Plaintiff GTG is an Australian corporation with a principal place of business in Victoria, Australia.
`
`2. Upon information and belief, Agilent is a corporation organized and existing under the laws of the state of Delaware,
`with its principal place of business located at 5301 Stevens Creek Boulevard, Santa Clara, California 95051. Agilent can
`be served with process through its registered agent, The Corporation Trust Company, Corporation Trust Center, 1209
`Orange Street, Wilmington, Delaware 19801.
`
`II. JURISDICTION AND VENUE
`
`3. This Court has exclusive jurisdiction of this action for patent infringement pursuant to 28 U.S.C. § 1338(a).
`
`4. This Court has jurisdiction over the subject matter of this action pursuant to 28 U.S.C. §§ 1331 and 1338(a).
`
`5. Venue is proper in this judicial district pursuant to 28 U.S.C. §§ 1391 and 1400.
`
`6. Upon information and belief, Agilent has minimum contacts with this judicial district such that this forum is a fair and
`reasonable one. Agilent has also each committed such purposeful acts and/or transactions in California that it reasonably
`
` © 2017 Thomson Reuters. No claim to original U.S. Government Works.
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`knew and/or expected that it could be hauled into court as a future consequence of such activity. Upon information and
`belief, Agilent has also transacted and/or, at the time of the filing of this Second Amended Complaint, is transacting
`business within the District of California. For these reasons, personal jurisdiction exists over Agilent and venue over this
`action is proper in this Court under 28 U.S.C. §§ 1391(b) and (c) and 28 U.S.C. § 1400(b).
`
`III. THE TECHNOLOGY
`
`7. This case involves technology related to deoxyribonucleic acid (“DNA”) and in particular the non-coding regions of
`DNA. Genetic information for all living things is stored in DNA. Four bases, adenine (A), cytosine (C), guanine (G) and
`thymine (T), (also known as nucleotides) are the building blocks of DNA. In order to form the double helix structure of
`DNA, the nucleotides form pairs with each other - G pairs with C and T pairs with A.
`
`8. DNA is replicated semi-conservatively via complementary strands according to basic Watson-Crick base pairing
`principles (A:T, G:C). Genes are the units of heredity and are stretches of the DNA of an organism that code for proteins
`or RNA molecules that have a function in the organism.
`
`9. The DNA of different individuals shows significant variation, and some variations in the coding regions of genes are
`associated with particular traits or diseases. An allele of a gene is one particular genetic variation of the coding region
`of that gene. It is thus important to be able to determine genetic differences, sometimes referred to as polymorphism,
`between individuals, and in particular their allelic status. A particularly common form of polymorphism is single
`nucleotide polymorphism (SNP), but other forms of polymorphism e.g., insertions and deletions (small indels, as well
`as larger genomic deletions and duplications), also exist. Early efforts at determining genetic polymorphism therefore
`focused on directly analyzing the coding region of genes to detect certain alleles of interest.
`
`10. In eukaryotes, sexual reproduction is often used to generate offspring with mixed genetic material from either parent.
`The majority of multicellular organisms are diploid for most of their lifespan - their cells have two copies of the genome
`and therefore two alleles of each gene. If both alleles of a particular gene are the same, the organism is homozygous at
`that genetic locus. If, on the other hand, the two alleles are different, the organism is heterozygous at that locus.
`
`11. During the process of sexual reproduction, diploid organisms produce haploid gamete cells (sperm and eggs where
`the genome is in single copy) by meiosis, which fuse after mating to reproduce diploid cells. Chromosomal crossover
`by homologous recombination in diploid gamete precursors means that duplicate chromosomes exchange stretches of
`DNA during meiosis. The various haploid cells so-produced thus harbor shuffled chromosomes. Certain regions of each
`chromosome tend to be inherited together, with rare crossover or shuffling sometimes occurring. These stretches of DNA
`are said to be linked, or in linkage disequilibrium.
`
`12. The term haplotype refers to the combination of alleles at adjacent loci that are inherited together. Thus haplotype
`defines a correlation between these alleles. Because of the common nature of SNPs, haplotype is also often taken to mean
`(the genotype of) a group of SNPs in linkage disequilibrium.
`
`13. Eukaryotic DNA comprises the regions of genes and intergenic regions between genes, both of which can include
`interspersed repeat sequences and repeat DNA motifs. Genes include regions coding for protein and non-coding regions.
`By way of illustration, a representative polymorphic partial genomic DNA sequence is shown below which has been
`adapted from H. K. Tabor, N. J. Risch, R. M. Myers Nature Reviews Genetics 2002, 3, 1-7.).
`
`TABLE
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` © 2017 Thomson Reuters. No claim to original U.S. Government Works.
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`The hypothetical promoter and partial gene shown above display single nucleotide polymorphism at four sites. SNPs
`1 and 4 are in non-coding regions - SNP 1 in an intergenic region and SNP4 in the first intron - and SNPs 2 and 3
`are in coding regions - both in the first exon. SNPs 2 and 3 contribute to phenotypic variation, and they are in linkage
`disequilibrium with SNPs 1 and 4 because a gene is a unit of inheritance, meaning that everything within the gene is
`linked and inherited as a block.
`
`14. The earliest filing date for U.S. Patent No. 5,612,179 (“the '179 Patent”) is August 25, 1989. The state of the art
`prior to August 25, 1989 can be appreciated from some of the literature of the time. Thus, for example, many molecular
`biology techniques were in use by 1989, such as the use of restriction endonucleases, cloning of genomic DNA, DNA
`sequencing, Southern blotting, and the use of probes in hybridisation assays. Restriction fragment length polymorphism
`was also used to directly investigate coding region polymorphism, protein sequencing using the Edman method and mass
`spectrometric sequencing was becoming an ever more useful tool. Enzyme-linked immunosorbent assays were then also
`used to detect polymorphism.
`
`15. Prior to the filing of the application for the '179 Patent, the prevailing opinion was that non-coding DNA was simply
`debris - 'junk DNA' - which was abundant because of a steady accumulation over evolutionary history. Genetic variation
`in the 'junk DNA' was known, but was dismissed as irrelevant.
`
`16. After years of research and substantial investment, the founders of GeneType AG proved that non-coding DNA is
`essential to the correct functioning of all cells. GeneType also showed that non-coding DNA variations may be linked
`to coding region alleles and that some variations in the non-coding regions may be used to detect diseases or traits that
`one associated with coding region variations. GeneType's discoveries enabled Dr. Malcolm Simons to invent and patent
`various methods by which polymorphisms found in the non-coding DNA of animals, humans and plants could be utilized
`to analyze coding region alleles of associated genes and to map gene traits of interest, including the '179 Patent.
`
`17. By way of example, Dr. Simons discovered that polymorphisms in non-coding DNA regions can be in linkage
`disequilibrium with polymorphisms in coding regions of DNA, and thus that alleles can be detected by analyzing the
`sequence of the non-coding region. SNP 4 of the hypothetical partial genomic sequence shown above in paragraph 13 is
`in linkage disequilibrium with SNPs 2 and 3, and if SNP 1 is also in linkage disequilibrium, then the genotypes of SNPs
`2 and 3 can be detected by determining the genotype of SNP1 or SNP4 as shown below.
`
`TABLE
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`The genotypes of SNPs 1-4 are thus correlated, and SNPs 1 and 4 are surrogate markers for SNPs 2 and 3.
`
`18. Before one can carry out the methods of the '179 Patent, the existence of the gene and the fact that it is polymorphic
`(multi-allelic) must be known, as does the sequence of the non-coding genomic DNA region. One also needs to have
`determined the fact that a non-coding polymorphism is serving as a surrogate marker for a desired physical characteristic,
`which is created by coding region DNA. The coding region allele or genotype produces a specific protein responsible for
`the phenotype which can be a disease trait or other desired characteristic.
`
`19. Throughout a genome, numerous groups of SNPs in linkage disequilibrium also show non-coding/coding genotypic
`correlations, but the specific details of each correlation are different because of differences between genes and different
`numbers, relative locations and genotypes of SNPs. There are also many instances where no such non-coding/coding
`genotypic correlation exists and this emphasizes the need to determine the details in relevant situations.
`
`20. Many genes are complex and there are often many haplotypes - an example of medium complexity chosen at random
`being the human SLC12A3 gene, as shown below in a figure taken from N. Tanaka et al. Diabetes 2003, 52, 2848-2853.
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` © 2017 Thomson Reuters. No claim to original U.S. Government Works.
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`TABLE
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`The genotypic correlations between non-coding and coding polymorphisms are, as shown above, therefore not generic
`and cannot be described by a mathematical relationship.
`
`21. Moreover, the correlation of non-coding DNA polymorphisms with coding region alleles is unlike Einstein's Law of
`Relativity, Archimedes' Principle of Buoyancy, or even the human body's metabolism of thiopurine drugs, all of which
`are generally applicable. Dissimilarly, linkage disequilibrium between non-coding and coding DNA is not ineluctable.
`Rather, any given linkage is specific to a particular region of the DNA of a group of individual organisms within
`a population of that species. Any given linkage is also not present in all species or even necessarily amongst other
`individuals of a particular species. Furthermore, any given linkage may not have existed in the past and may not exist in
`the future, as evolutionary inherency may transform the linkage. Finally, one non-coding polymorphism may indicate
`one, several or many haplotypes.
`
`22. Despite this, the '179 Patent reveals the discovery that non-coding region polymorphisms can be used as surrogate
`markers for coding region polymorphisms on a case-by-case basis if the sequence of the non-coding region containing
`the polymorphism is known. The inventions of the '179 Patent are based on this discovery. However, it is limited only
`to very specific methods for the direct determination of the surrogate markers and the combination was not in use at
`the time of the invention of the '179 Patent.
`
`23. Additionally, limitations recited in the claims of the '179 Patent were used in a novel way. Several claims of the '179
`Patent require the use of a primer pair. A primer is an oligonucleotide, or short strand of nucleotides, which binds to a
`specific point on a DNA strand (“original strand”) to be amplified. The primer is a man-made tool used to amplify a
`portion of a DNA or RNA strand. The primer is a complementary nucleotide sequence strand (based on the Watson-
`Crick pairing) to the initial and/or end portions of the original strand to be copied. A DNA polymerase then adds the
`next complementary nucleotide to the end of the primer. Primer pairs have two primers, one used to replicate from the
`3' end of the original strand and one to replicate from the (complement of the) 5' end of the original strand. Though
`primer pairs may indicate the use of polymerase chain reaction (PCR) for amplification, primers may be used in multiple
`applications to hybridize DNA.
`
`24. Generally, when primer pairs are used in PCR amplification, the double helix structure of the original strand of
`DNA is denatured, so that the two original strands are separated. One primer attaches to the complementary sequence
`on one of the original strands and the second primer attaches to the complementary sequence on the other original
`strand. After a polymerase is added, nucleotides are added to one end of each primer to create a replicate copy of its
`respective strand. The original strands and the replicated strands are then again denatured. This time, primers attach
`to the complementary sequence on the 3' end of the original strand, the complementary sequence on the 5' end of the
`original strand, the complementary sequence on the 3' end of the replicated strand and the complementary sequence on
`the 5' end of the replicated strand. After the strands are again denatured, shorter replicated strands are created that only
`include the complementary sequence of the primers and the nucleotides between the primers. The denaturing, primer
`addition, and replication steps are repeated to amplify the copied DNA strands. There are many variations on the basic
`PCR technique, all of which result in amplification of the extracted genomic DNA. These replicated strands are synthetic
`and do not appear in nature in that form, as they may be only a portion of a DNA strand or fragmented and chemically
`different copies of the naturally occurring form.
`
`25. The combinations recited in the claims of the '179 Patent were neither routine nor conventional at the time of the
`earliest filed application that resulted in the '179 Patent. PCR was known. However, no one had used a primer pair to
`amplify non-coding DNA to define a DNA sequence in genetic linkage with a coding region allele in order to detect that
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`allele. Furthermore, amplification was not inherent or necessary to utilizing the correlation between the polymorphism
`in the non-coding region and the polymorphism in the coding region.
`
`26. One claimed method of the '179 Patent - Claim 1 - involves the detection of at least one coding region allele of a multi-
`allelic genetic locus by amplifying a region of non-coding DNA with a primer pair, and then analyzing the amplified
`sequence to detect the allele. Claim 1 first requires “amplif [ication of] genomic DNA with a primer pair that spans a
`non-coding region sequence.” Second, the primer pair has to define “a DNA sequence which is in genetic linkage with
`said genetic locus and contain a sufficient number of non-coding region sequence nucleotides to produce an amplified
`DNA sequence characteristic of said allele.” Third, “the amplified DNA sequence [must be analyzed] to detect the allele.”
`Claim 1 of the '179 Patent thus does not simply describe a law of nature or natural phenomenon. Rather, it describes
`very specific steps for exploiting the discovery that “intron sequences that exhibit linkage disequilibrium with adjacent
`and remote loci can be used to detect alleles of those loci.”
`
`27. Claim 1 of the '179 Patent requires amplification of genomic DNA with a primer pair. The process of amplification
`requires a machine (for example a PCR machine) and transforms regions of native genomic DNA extracted from an
`organism into synthetic DNA fragments using a pair of synthetic oligonucleotide primers. The DNA of most species is
`methylated at the 5'-position of a fraction of cytosines across the genome. This methylation affects the function of the
`DNA, e.g. gene expression, and provides additional epigenetic regulation needed to govern the development of multiple
`cell types. When genomic DNA is amplified with a primer pair, the methylation is not copied and the synthetic DNA
`fragments carry cytosine at those positions corresponding to 5'-methylcytosine in the genomic DNA. Thus unmethylated
`synthetic DNA is man-made and different from the methylated naturally occurring DNA from which it was produced
`by amplification
`
`28. At the time of the earliest filing of an application that resulted in the '179 Patent, numerous methods were
`available and used to analyze both coding and non-coding region polymorphism that do not use DNA and primer pair
`amplification:
`
`1. Protein sequencing - in this method, the proteinaceous gene product is sequenced directly by determining the order of
`its constituent amino acids. Polymorphism at the genetic level manifests itself in the form of proteins with amino acid
`differences at a specific position.
`
`2. Immunological methods - in such methods, the different binding of polymorphs of a protein to antibodies enables
`their identification. A particularly widely used immunological method - enzyme-linked immunosorbent assay (ELISA)
`- uses a heterogeneous, solid-phase enzyme immunoassay to detect the allele.
`
`3. Northern blotting - in this method, RNA is electrophoretically separated by size, transferred ('blotted') to a membrane
`and interrogated by hybridisation to a labeled probe. The probe/s has/have a sequence complementary to the region of
`that RNA which is polymorphic and can discriminate alleles. Probes can be DNA, RNA or oligonucleotides. Because
`of incomplete splicing, intronic polymorphisms can be detected in this way.
`
`29. There are also a number of methods for the detection of non-coding polymorphisms that do not require primer pair
`amplification that were available and used at the time of the filing of the applications for the Patents, these included:
`
`1. Restriction fragment length polymorphism (RFLP) - this method exploits the sequence specificity of a large family
`of DNA cleaving enzymes known as restriction endonucleases. Restriction endonucleases recognize a short sequence of
`DNA - usually a 6 base pair palindrome. Because the short sequence occurs many times throughout a genome, restriction
`endonucleases cleave genomic DNA into a multitude of fragments. Polymorphism can destroy or create a restriction
`site and therefore be detected by a change in length of fragments. Thus, to detect polymorphisms using RFLP, genomic
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`DNA samples are digested with one or more restriction endonucleases and the resultant fragments are electrophoretically
`separated, Southern blotted onto a membrane and interrogated by hybridisation to a probe.
`
`2. Sequencing of cloned DNA - in this method, genomic DNA is cleaved with restriction endonucleases and 'shotgun'
`cloned into a vector such as a plasmid, bacteriophage or cosmid. Colony screening then enables clones containing the
`DNA region of interest to be identified and direct sequencing of insert DNA of clones from different individuals then
`enables polymorphisms to be detected.
`
`30. As mentioned in the foregoing, in RFLP analysis it is common to use restriction endonucleases that recognize and
`cleave a specific six base pair palindromic sequence. Any specific six base pair sequence occurs on average every about
`four kilobases in genomic DNA ceteris paribus (there are four different bases in DNA, and if summation of GC is equal to
`the summation of AT, 4 6 = 4096). RFLP analysis therefore usually relies on fragments greater than about two kilobases
`in length to detect polymorphisms.
`
`31. The use of Third Wave (now Hologic) Invader Technology - which uses two oligonucleotides and signal amplification
`to detect alleles through non-coding polymorphisms also does not require primer pair amplification. The Invader
`technology is composed of two simultaneous isothermal reactions. A primary reaction detects polymorphisms associated
`with a specific region of the target DNA. A second reaction is used for generic readout and signal amplification. If the
`variation or sequence in question is present, an overlapping structure is created with a probe and the Invader oligo on
`the target DNA region or sequence. The Invader Cleavase enzymes specifically cleave the primary probes that form
`overlapping structures with the Invader oligo, releasing the 5' flaps plus one nucleotide. In the absence of the specific
`target, no flap is released. The number of flaps released is relative to the amount of target in the sample, allowing for
`quantitative detection of the target non-coding polymorphism. Furthermore, the pending technology of nanopore single
`molecule DNA sequencing will not infringe the claims of the '179 Patent if used for detection of alleles through non-
`coding polymorphisms.
`
`IV. THE PATENT-IN-SUIT
`
`32. On March 18, 1997, the '179 Patent was duly and legally issued for an “Intron Sequence Analysis Method for
`Detection of Adjacent Locus Alleles as Haplotypes.” A true and correct copy of the '179 Patent is attached as Exhibit A.
`
`33. GTG is the owner of the '179 Patent by assignment from Genetype AG, who was originally assigned the technology
`by the inventor Dr. Malcolm Simons, with the exclusive right to enforce and collect damages for infringement of the
`'179 Patent during all relevant time periods.
`
`34. The '179 Patent claims patentable subject matter under 35 U.S.C. § 101.
`
`35. The '179 Patent is presumed valid and enforceable pursuant to 35 U.S.C. § 282.
`
`36. The '179 Patent generally relates to methods of analysis of non-coding DNA sequences.
`
`37. The Abstract of the '179 Patent relevantly provides:
`
`The present invention provides a method for detection of at least one allele of a genetic locus and can be used to provide
`direct determination of the haplotype. The method comprises amplifying genomic DNA with a primer pair that spans
`an intron sequence and defines a DNA sequence in genetic linkage with an allele to be detected. The primer-defined
`DNA sequence contains a sufficient number of intron sequence nucleotides to characterize the allele. Genomic DNA is
`amplified to produce an amplified DNA sequence characteristic of the allele. The amplified DNA sequence is analyzed to
`detect the presence of a genetic variation in the amplified DNA sequence such as a change in the length of the sequence,
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` © 2017 Thomson Reuters. No claim to original U.S. Government Works.
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`gain or loss of a restriction site or substitution of a nucleotide. The variation is characteristic of the allele to be detected
`and can be used to detect remote alleles.
`
`38. Without limitations of the claims to be asserted in this action, and for exemplary purposes only, Independent Claim
`1 of the '179 Patent reads:
`
`1. A method for detection of at least one coding region allele of a multi-allelic genetic locus comprising: a) amplifying
`genomic DNA with a primer pair that spans a non-coding region sequence, said primer pair defining a DNA sequence
`which is in genetic linkage with said genetic locus and contains a sufficient number of non-coding region sequence
`nucleotides to produce an amplified DNA sequence characteristic of said allele; and b) analyzing the amplified DNA
`sequence to detect the allele.
`
`39. The '179 Patent was previously asserted by GTG in the matter of Genetic Technologies Ltd. v. Applera Corp., Case
`No. C 03-1316-PJH, in the United States District for the Northern District of California (the “Applera Action”). The
`Applera Action was ultimately settled with Applera Corporation taking a license to the '179 Patent, among others.
`
`40. The '179 Patent was the subject of a declaratory judgment action initiated by Monsanto in the matter of Monsanto
`Company v. Genetic Technologies Ltd., Case No. 06-cv-00989-HEA, in the United States District Court for the Eastern
`District of Missouri, Eastern Division (the “Monsanto Action”). That Monsanto Action was ultimately settled.
`Monsanto has now taken three licenses to the '179 Patent, among others.
`
`41. The '179 Patent was most recently asserted by GTG in the matter of Genetic Technologies Ltd. v. Beckman Coulter,
`Inc., et al, Case No. 10-cv-0069-BBC, in the United States District Court for the Western District of Wisconsin (the
`“Beckman Coulter Action”). The Beckman Coulter Action was resolved with at least Beckman Coulter, Inc., Gen-Probe,
`Inc., Interleukin Genetics Incorporated, Molecular Pathology Laboratory Network, Inc., Orchid Cellmark, Inc., Pioneer
`Hi-Bred International, Inc., and Sunrise Medical Laboratories, Inc. all taking a license to the '179 Patent, among others.
`GTG has secured over $14.5 million in licensing revenue since the filing of the Beckman Coulter Action in 2010.
`
`42. In addition to the licenses identified in the preceding paragraphs, the '179 Patent and related patents have been licensed
`to at least the following entities: AgResearch Ltd.; ARUP Laboratories, Inc.; Australian Genome Research Facility Ltd.;
`Bio Reference Laboratories (subsidiary GeneDx); Bionomics Ltd.; BioSearch Technologies Inc.; Pfizer Animal Health;
`C Y O'Connor ERADE Village Foundation (incorporating the Immunogenetics Research Foundation and the Institute
`of Molecular Genetics and Immunology Incorporated); Crop and Food Research Ltd.; DNA Diagnostics Ltd.; General
`Electric Co. and its subsidiary GE Healthcare Bio-Sciences Corp.; Genosense Diagnostics GmbH; Genzyme Corp.;
`Innogenetics N.V.; Kimball Genetics, Inc.; Laboratory Corporation of America Holdings, Inc.; Livestock Improvement
`Corporation Ltd.; MetaMorphix, Inc.; Millennium Pharmaceuticals Inc.; Myriad Genetics, Inc.; Nanogen, Inc.; New
`Zealand Blood Service; Optigen, L.L.C.; Ovita Ltd.; Perlegen Sciences, Inc.; Prometheus Laboratories Inc.; Qiagen, Inc.;
`Quest Diagnostics Inc.; Sciona, Inc.; Sequenom, Inc.; Syngenta Crop Protection AG; Thermo Fisher Scientific Inc.; TIB
`MOLBIOL Syntheselabor GmbH; Tm Bioscience Corporation; Gen-Probe, Inc.; and others.
`
`43. On May 10, 2012, a second Ex Parte Reexamination of certain Claims 1-18 and 26-32 of the '179 Patent was requested
`by Merial Ltd. That Ex Parte Reexamination request was granted on June 28, 2012. On March 29, 2013, the USPTO
`issued an Ex Parte Reexamination Certificate confirming all of the reexamined claims. A true and correct copy of the
`March 29, 2013 Reexamination Certificate is attached as Exhibit B. On March 1, 2013, a third Ex Parte Reexamination
`of Claims 1-18 and 26-32 of the '179 Patent was requested by Merial. On September 19, 2013, the USPTO issued an Ex
`Parte Reexamination Certificate confirming all of the claims that were the subject of this Reexamination. A true and
`correct copy of the Reexamination Certificate is attached as Exhibit C.
`
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`44. The '179 Patent expired on March 9, 2010. However, GTG remains entitled to collect damages for past infringement
`occurring during the term of the '179 Patent pursuant to 35 U.S.C. §§ 284 and 286. Specifically, for infringement occurring
`in the period commencing six years prior to the filing date of GTG's original Complaint against Agilent, i.e., May 25,
`2005, through March 9, 2010.
`
`V. AGILENT'S INFRINGEMENT
`
`45. Upon information and belief, and as further described below, Agilent has manufactured, made, had made, used,
`practiced, imported, provided, supplied, distributed, sold, and/or offered for sale products and/or services in the United
`States that directly infringed one or more of Claims 1-13 and 15-18 of the '179 Patent; and/or Agilent has induced and/or
`contributed to the infringement of one or more of Claims 1-13 and 15-18 of the '179 Patent by others in the United States.
`
`46. Agilent acquired Stratagene Corporation (“Stratagene”) in June of 2007, and Stratagene became part of Agilent's Bio-
`Analytical Measurements business group. According to Stratagene marketing materials, “[i]t offers products in various
`categories, including amplification, cloning, nucleic acid analysis, quantitative PCR, cell biology, microarrays, and
`protein function and analysis. [Stratagene] also provides software for pathway analysis and microarray data analysis.”
`
`47. In 2008, $2.3 billion of Agilent's net revenue was attributed to its Bio-Analytical Measurement business group,
`which provides “instruments, software, consumables and services that enable customers to identify, quantify and analyze
`the physical and biological properties of substances and products.” In 2009, $2.1 billion of Agilent's net revenue
`was attributed to its Bio-Analytical Measurement business group. In 2010, $1.5 billion of Agilent's net revenue was
`attributed to its Life Science business group, which includes “liquid chromatography, mass spectrometry, microarrays,
`polymerase chain reaction (PCR) instrumentation, related bioreagents, electrophoresis, laboratory automation and
`robotics, software and informatics, nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) systems,
`and related consumables and services.” Many of the Agilent products responsible for these revenues were utilized by
`Agilent customers with Agilent's knowledge and encouragement to practice methods that infringed upon the '179 Patent.
`
`48. By way of example only, and upon information and belief, the Agilent 2100 Bioanalyzer product has been used by
`Agilent or an Agilent customer to determine a single nucleotide polymorphism, specifically the G20210A mutation. In
`2005, Agilent published an Application Note describing “how the Agilent 2100 bioanalyzer can be used for the detection
`of a point mutation in the human prothrombin gene. ... A single nucleotide polymorphism (SNP), i.e. a point mutation
`in the prothrombin gene results in a common hereditary predisposition to venous thrombosis.” This SNP mutation is
`“in the untranslated part of the prothrombin gene.” These activities directly read on the claims of the '179 Patent and
`therefore infringe the '179 Patent as illustrated, for exemplary purposes only, with regard to Claim 1 of the '179 Patent
`in the Table below:
`
`Claim 1
` 
`
`A method for detection of at least one
`coding region allele of a multi-allelic genetic
`locus comprising:
` 
`
`a) amplifying genomic DNA with a primer
`pair that spans a non-coding region
`sequence,
` 
`
`Statements in Application Note “Detection of
`a point mutation in the prothrombin gene with
`the Agilent 2100 bioanalyzer”
` 
`The G20210A mutation in the untranslated
`part of the multi-allelic prothrombin gene
`results in an elevated serum prothrombin
`level and an increased risk for venous
`thrombosis