Case3:12-cv-00132-SI Document133 Filed10/16/13 Page1 of 44
`
`IN THE UNITED STATES DISTRICT COURT
`FOR THE NORTHERN DISTRICT OF CALIFORNIA
`No. C 11-06391 SI
`ARIA DIAGNOSTICS, INC.,
`CLAIM CONSTRUCTION ORDER
`Plaintiff,
`
`No. C 12-00132 SI
`
`No. C 12-00865 SI
`
`No. C 12-05501 SI
`
` v.
`SEQUENOM, INC.,
`Defendant/Counterclaimant.
` /
`NATERA, INC. and DNA DIAGNOSTICS
`CENTER, INC.,
`Plaintiffs/Counterclaim-
`Defendants,
`
` v.
`SEQUENOM, INC. and ISIS INNOVATION
`LIMITED,
`
`Defendants/Counterclaimants.
` /
`VERINATA HEALTH, INC. and THE BOARD
`OF TRUSTEES OF THE LELAND
`STANFORD JUNIOR UNIVERSITY,
`Plaintiffs,
`
` v.
`SEQUENOM, INC. and SEQUENOM CENTER
`FOR MOLECULAR MEDICINE, LLC,
`Defendants/Counterclaimants.
` /
`VERINATA HEALTH, INC. and THE BOARD
`OF TRUSTEES OF THE LELAND
`STANFORD JUNIOR UNIVERSITY,
`Plaintiffs,
`
` v.
`ARIOSA DIAGNOSTICS, INC. and
`LABORATORY CORPORATION OF
`AMERICA HOLDINGS,
`Defendants/Counterclaimants.
` /
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`For the Northern District of California
`For the Northern District of California
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`United States District Court
`United States District Court
`
`Petitioner Sequenom - Ex. 1016, p. 1
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`

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`Case3:12-cv-00132-SI Document133 Filed10/16/13 Page2 of 44
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`On September 12, 2013 and September 16, 2013, the Court held Markman hearings regarding
`the construction of disputed claim terms in six patents teaching techniques for non-invasive prenatal
`testing. Having considered the arguments of counsel and the papers submitted, the Court construes the
`disputed claim terms as follows.
`
`BACKGROUND
`
`1.
`
`Procedural Background
`This dispute began in 2011, when Ariosa1 filed a declaratory relief action against Sequenom,
`seeking a declaration that its “Harmony Test” does not infringe any claims of U.S. Patent No. 6,258,540
`(“the ’540 patent”). Aria Diagnostics, Inc. v. Sequenom, Inc., C 11-6391-SI (filed Dec. 19, 2011).
`Sequenom filed a counterclaim against Ariosa, asserting infringement of the ’540 patent. Subsequently,
`two other companies, Natera and Verinata, also filed declaratory judgment actions in this Court seeking
`judgments that their products do not infringe Sequenom’s ’540 patent and asserting that the ’540 patent
`is invalid. See Natera Inc. v. Sequenom, Inc., C 12-0132-SI (filed Jan. 6, 2012) (regarding the “Non-
`Invasive Paternity Test”); Verinata Health, Inc. v. Sequenom, Inc. (Verinata I), C 12-0865-SI (filed Feb.
`22, 2012) (regarding the “Verifi Prenatal Test”). Sequenom also filed counterclaims that Natera, DNA
`Diagnostics Center, Verinata, and Stanford are infringing the ’540 patent. See id.
`Additionally, in Verinata I, Verinata and Stanford allege that Sequenom is infringing U.S.
`Patent Nos. 7,888,017 (“the ’017 patent”), 8,008,018 (“the ’018 patent”), and 8,195,415 (“the ’415
`patent”). Finally, Verinata and Stanford also filed a case alleging that Ariosa and LabCorp are
`infringing U.S. Patent Nos. 8,296,076 (“the ’076 patent”) and 8,318,430 (“the ’430 patent”). See
`Verinata Health, Inc. v. Ariosa Diagnostics, Inc. (Verinata II), C 12-5501-SI (filed Oct. 25, 2012).
`
`2.
`
`Factual Background
`These patents all involve methods to conduct non-invasive prenatal DNA testing. Fetal DNA
`
`1 Formerly known as Aria Diagnostics, Inc.
`
`2
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`Case3:12-cv-00132-SI Document133 Filed10/16/13 Page3 of 44
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`testing can aid sex determination, blood typing and other genotyping, and detection of pre-eclampsia
`in the mother. It can also detect fetal aneuploidy, which is a disorder in which the fetus has an abnormal
`number of chromosomes, instead of the normal 23 pairs. Common aneuploidy disorders include Down
`syndrome (a third copy, or “trisomy,” of chromosome 21), Edwards syndrome (a third copy of
`chromosome 18), and Patau syndrome (a third copy of chromosome 13).
`Prior to these patents, testing fetal DNA required invasive techniques that took samples from the
`fetus or placenta. However, invasive prenatal testing presented risks to both the fetus and the mother.
`Scientists began researching various techniques to make these prenatal diagnoses non-invasively.
`Initially, non-invasive research had focused on detecting fetal cells that had passed through the amniotic
`sac into the mother’s bloodstream. The fetal cells then had to be separated from the much more
`common maternal cells. This process of isolating intact fetal cells was labor-intensive and produced
`unreliable results.
`The ’540 patent followed the discovery in 1996-1997 by Drs. Lo and Wainscoat that fetal DNA
`is detectable in maternal serum or plasma samples in extra-cellular or cell-free form. According to
`Sequenom, prior non-invasive research had focused on detecting fetal cells because the presence of cell-
`free fetal DNA was not known. Evans Decl. ¶ 40. Therefore, the significance of the discovery by Drs.
`Lo and Wainscoat was that the process of isolating fetal cells was not necessary because fetal DNA was
`present outside of cells, as “extracellular” or “cell-free DNA” suspended together with the mother’s
`DNA in the maternal bloodstream. This was a more efficient and reliable method then previous non-
`invasive techniques.
`A decade later, Drs. Quake and Fan at Stanford further advanced the science in non-invasive
`prenatal testing using molecular counting techniques. Previously, researchers had believed that because
`aneuploidies do not present a mutational change in the DNA sequence (but are merely a change in the
`number of chromosomes), they would need to distinguish fetal DNA from maternal DNA in order to
`diagnose fetal aneuploidy non-invasively. The Stanford researchers used advanced DNA sequencing
`techniques, such as digital polymerase chain reaction (“PCR”) and massive parallel sequencing. They
`discovered a method to diagnose fetal aneuploidy through their molecular counting techniques, without
`needing to distinguish the maternal DNA from the fetal DNA. Stanford and Verinata claim that these
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`Petitioner Sequenom - Ex. 1016, p. 3
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`Case3:12-cv-00132-SI Document133 Filed10/16/13 Page4 of 44
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`techniques are much more efficient and effective than those utilized previously. They further refined
`their method by teaching how to correct for sequence tag density variances, how to selectively analyze
`specific DNA sequences, and how to generate a library from a pool of multiple samples. These
`advancements further increased the accuracy and the efficiency of the prenatal tests.
`
`LEGAL STANDARD
`Claim construction is a matter of law. Markman v. Westview Instr., Inc., 517 U.S. 370, 372
`(1996). Terms contained in claims are “generally given their ordinary and customary meaning.”
`Phillips v. AWH Corp., 415 F.3d 1303, 1312 (Fed. Cir. 2005). “[T]he ordinary and customary meaning
`of a claim term is the meaning that the term would have to a person of ordinary skill in the art in
`question at the time of the invention.” Id. at 1312. In determining the proper construction of a claim,
`a court begins with the intrinsic evidence of record, consisting of the claim language, the patent
`specification, and, if in evidence, the prosecution history. Id. at 1313; see also Vitronics Corp. v.
`Conceptronic, Inc., 90 F.3d 1576, 1582 (Fed. Cir. 1996). “The appropriate starting point . . . is always
`with the language of the asserted claim itself.” Comark Communications, Inc. v. Harris Corp., 156 F.3d
`1182, 1186 (Fed. Cir. 1998); see also Abtox, Inc. v. Exitron Corp., 122 F.3d 1019, 1023 (Fed. Cir.
`1997).
`
`Accordingly, although claims speak to those skilled in the art, claim terms are construed in light
`of their ordinary and accustomed meaning, unless examination of the specification, prosecution history,
`and other claims indicates that the inventor intended otherwise. See Electro Medical Systems, S.A. v.
`Cooper Life Sciences, Inc., 34 F.3d 1048, 1053 (Fed. Cir. 1994). The written description can provide
`guidance as to the meaning of the claims, thereby dictating the manner in which the claims are to be
`construed, even if the guidance is not provided in explicit definitional format. SciMed Life Systems, Inc.
`v. Advanced Cardiovascular Systems, Inc., 242 F.3d 1337, 1344 (Fed. Cir. 2001). In other words, the
`specification may define claim terms “by implication” such that the meaning may be “found in or
`ascertained by a reading of the patent documents.” Vitronics, 90 F.3d at 1584 n.6.
`In addition, the claims must be read in view of the specification. Markman, 52 F.3d at 978.
`Although claims are interpreted in light of the specification, this “does not mean that everything
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`Case3:12-cv-00132-SI Document133 Filed10/16/13 Page5 of 44
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`expressed in the specification must be read into all the claims.” Raytheon Co. v. Roper Corp., 724 F.2d
`951, 957 (Fed. Cir. 1983). For instance, limitations from a preferred embodiment described in the
`specification generally should not be read into the claim language. See Comark, 156 F.3d at 1187.
`However, it is a fundamental rule that “claims must be construed so as to be consistent with the
`specification.” Phillips, 415 F.3d at 1316. Therefore, if the specification reveals an intentional
`disclaimer or disavowal of claim scope, the claims must be read consistently with that limitation. Id.
`Finally, the Court may consider the prosecution history of the patent, if in evidence. Markman,
`52 F.3d at 980. The prosecution history limits the interpretation of claim terms so as to exclude any
`interpretation that was disclaimed during prosecution. See Southwall Technologies, Inc. v. Cardinal IG
`Co., 54 F.3d 1570, 1576 (Fed. Cir. 1995). In most situations, analysis of this intrinsic evidence alone
`will resolve claim construction disputes. See Vitronics, 90 F.3d at 1583. Courts should not rely on
`extrinsic evidence in claim construction to contradict the meaning of claims discernable from
`examination of the claims, the written description, and the prosecution history. See Pitney Bowes, Inc.
`v. Hewlett-Packard Co., 182 F.3d 1298, 1308 (Fed. Cir. 1999) (citing Vitronics, 90 F.3d at 1583).
`However, it is entirely appropriate “for a court to consult trustworthy extrinsic evidence to ensure that
`the claim construction it is tending to from the patent file is not inconsistent with clearly expressed,
`plainly apposite, and widely held understandings in the pertinent technical field.” Id. Extrinsic
`evidence “consists of all evidence external to the patent and prosecution history, including expert and
`inventor testimony, dictionaries, and learned treatises.” Phillips, 415 F.3d at 1317. All extrinsic
`evidence should be evaluated in light of the intrinsic evidence. Id. at 1319.
`
`DISCUSSION
`
`1.
`
`Sequenom’s ’540 Patent
`Sequenom is the exclusive licensee of the ’540 patent, which Sequenom licensed from Isis
`Innovation Limited. The ’540 patent is entitled “Non-Invasive Prenatal Diagnosis,” and was issued to
`Drs. Yuk-Ming Dennis Lo and James Stephen Wainscoat on July 10, 2001. The patent “relates to a
`detection method performed on a maternal serum or plasma sample from a pregnant female, which
`method comprises detecting the presence of a nucleic acid of foetal origin in the sample.” The ’540
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`Patent, Abstract. “This invention enables non-invasive prenatal diagnosis, including for example sex
`determination, blood typing and other genotyping, and detection of pre-eclampsia in the mother.” Id.
`The ’540 Patent application was originally filed in 1998, and underwent two rounds of rejections
`before the patent issued in 2001. In that process, the PTO required the applicants to include the
`limitation “paternally inherited” in claims where the applicants had wanted to use simply “nucleic acid”
`or “foetal nucleic acid.” The PTO also required the applicants to add “amplifying.”
`Relevant for the purposes of this motion, the ’540 patent claims the following:
`Claim 1. A method for detecting a paternally inherited nucleic acid of fetal origin
`performed on a maternal serum or plasma sample from a pregnant female, which method
`comprises
`amplifying a paternally inherited nucleic acid from the serum or plasma sample and
`detecting the presence of a paternally inherited nucleic acid of fetal origin in the
`sample.
`Claim 8. The method according to claim 1, wherein the presence of a foetal nucleic acid
`from a paternally-inherited non-Y chromosome is detected.
`Claim 13. The method according to claim 5, which comprises determining the
`concentration of the foetal nucleic acid sequence in the maternal serum or plasma.
`Claim 19. The method according to claim 1, wherein the sample contains foetal DNA
`at a fractional concentration of total DNA of at least about 0.14%, without subjecting it
`to a foetal DNA enrichment step.
`The ’540 Patent 23:60-67, 25:39-42 (the construction of the highlighted terms is disputed by the parties).
`Most of the claims are dependent on claim 1. The parties agree that terms should be construed
`consistently across all claims, and that “according to the method of claim 1” from claim 21 means
`“claim 21 is dependent on claim 1 and therefore incorporates all the limitations of claim 1.”
`On July 5, 2012, the Court denied Sequenom’s motion for a preliminary injunction, in the course
`of which it preliminarily construed two terms from the ’540 patent, “paternally inherited nucleic acid”
`and “amplifying.” Sequenom appealed the Court’s order. On August 9, 2013, the Federal Circuit issued
`an order rejecting the Court’s initial claim construction. Aria Diagnostics, Inc. v. Sequenom, Inc., No.
`2012-1531, 2013 WL 4034379 (Fed. Cir. Aug. 9, 2013). The Federal Circuit found that “paternally
`inherited nucleic acid” did not need to be known in advance to have been inherited only from the father.
`Id. at *2-5. The Federal Circuit also found the term “amplifying” was not limited to increasing the
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`Petitioner Sequenom - Ex. 1016, p. 6
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`concentration, but more broadly means increasing the amount. Id. at *5-6. The Court construes these
`terms and other disputed terms in the ’540 patent in accordance with the Federal Circuit order.
`“Paternally inherited nucleic acid,” therefore, is construed as “a nucleic acid that originates
`from the fetus and is inherited from the father.”2 “Amplifying,” therefore, is construed as “increasing
`the amount of the nucleic acid by making copies of it.”
`The parties dispute the construction of four other terms.
`
`A.
`
`“Detecting”
`
`Verinata’s
`Proposed
`Construction
`“isolating and
`identifying any
`paternal nucleic
`acid by
`comparison to
`maternal
`characteristics”
`
`Sequenom’s
`Proposed
`Construction
`Construe
`“detecting” as:
`“discovering or
`determining the
`existence,
`presence, or fact
`of”
`See above for
`“paternally
`inherited nucleic
`acid.”
`“Subjecting” and
`“test” have their
`ordinary and
`customary
`meanings
`
`Ariosa’s
`Proposed
`Construction
`“discovering (the
`presence of) a
`DNA sequence
`known to be
`received only
`from the father
`which is not
`possessed by the
`mother; the
`discovering is
`not based on
`differences
`between maternal
`and fetal DNA”
`
`Natera/DDC’s
`Proposed
`Construction
`“discovering (the
`presence of) a
`fetal DNA
`sequence from a
`primer binding
`region inherited
`from the father
`and previously
`known to not be
`possessed by the
`mother; the
`discovering is
`not based on
`differences
`between maternal
`and fetal DNA”
`
`Claim Term
`
`“detecting” /
`“detecting a
`paternally
`inherited nucleic
`acid” / “detecting
`the presence of a
`paternally
`inherited nucleic
`acid of fetal
`origin in the
`sample” / “to
`detect paternally
`inherited nucleic
`acid” /
`“subjecting the
`amplified nucleic
`acid to a test for
`the paternally
`inherited nucleic
`acid”
`[Claims 1, 4, 5,
`8, 15, 18, 21, 24,
`25]
`
`2 Subsequent to the Federal Circuit’s opinion, the parties revised several of their proposed
`constructions. Natera currently proposes that this term be construed as “a fetal DNA sequence from a
`primer binding region inherited from the father and previously known to not be possessed by the
`mother.” However, the Court finds that it is bound by the findings of the Federal Circuit, which require
`these constructions. Natera’s modified proposal is not consistent with the Federal Circuit opinion.
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`Sequenom, Ariosa, and Natera essentially agree that detecting means discovering, but disagree
`about whether the detecting can be based on differences between maternal and fetal DNA. Verinata’s
`amended proposed construction is based on language from the Federal Circuit’s order.
`Ariosa and Natera argue that the limitation “the discovering is not based on differences between
`maternal and fetal DNA” is required to ensure that the claims are limited to the detection of fetal nucleic
`acid known to be received from the father and not possessed by the mother. They also variously add the
`phrases “known to be received only from the father” or “previously known to not be possessed by the
`mother” to accomplish this same purpose. They cite to the prosecution history and specification as
`support for their proposed constructions. This is essentially the same argument that the parties made
`in their proposed construction for “paternally inherited nucleic acid.”
`The Federal Circuit has rejected an interpretation of the prosecution history requiring that the
`paternal origin be known in advance, finding the prosecution events “ambiguous.” Aria Diagnostics,
`2013 WL 4034379, at *4 (“This [prosecution history] record does not clearly require that the paternally
`inherited sequence must have been known in advance to have come from the father. The account of the
`prosecution history makes no reference to advance timing, let alone the clear and unmistakable
`disavowal required by controlling precedent.”). The Federal Circuit also rejected the argument that this
`known in advance limitation was required by the specification or the examples. Id. at 3-4.
`Thus, the parties cannot add the same “known in advance” limitation to the “detecting” term.
`It is not supported by the plain language of the term. There is not a clear limitation that the paternal
`inheritance must be known in advance or that the detecting cannot be not based on differences between
`maternal and fetal DNA.
`Verinata’s proposed construction is taken from the following portion of the Federal Circuit
`opinion: “Properly understood, this sentence describes the method of isolating and identifying any
`paternal characteristics by comparison to maternal characteristics, hardly a limitation to only paternal
`characteristics known in advance.” Id. at *4 (emphasis in original). However, this passage explains the
`meaning of a sentence in the specification; it does not construe the “detecting” term or any other claim
`term. Moreover, this proposed construction is not supported by the claim or specification. The word
`“identifying” is never used in the patent, and nothing in the specification requires limiting the scope of
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`detecting is limited only to “comparison to maternal characteristics.” Even if all of the examples detect
`through a comparison to maternal characteristics, the Federal Circuit opinion is clear that these examples
`do not limit the claim scope. See id. at *3 (“Instead of a clear intention to limit the claims to the
`embodiments in the examples, here the specification states that the examples ‘do not in any way limit
`the scope of the invention.’”).
`“Detecting,” therefore is construed as “discovering or determining the existence, presence, or
`
`fact of.”
`
`B.
`
`“Foetal DNA Enrichment Step”
`
`Sequenom’s
`Proposed
`Construction
`“increasing the
`concentration of
`fetal DNA
`relative to the
`maternal DNA in
`the sample”
`See above
`
`Ariosa’s
`Proposed
`Construction
`See below
`
`Verinata’s
`Proposed
`Construction
`See below
`
`Natera/DDC’s
`Proposed
`Construction
`Because claim 19
`is not asserted in
`this case, it is not
`appropriate to
`construe this
`term.
`
`“prior to the
`amplification
`step of claim 1”
`
`“prior to the
`amplification
`step of claim 1”
`
`Claim Term
`
`“foetal DNA
`enrichment step”
`[Claim 19]
`
`“without
`subjecting it to a
`foetal DNA
`enrichment step”
`[Claim 19]
`
`The parties’ dispute regarding the term “foetal DNA enrichment step” is essentially a
`continuation of the argument previously made about “amplifying.” Sequenom argues that enrichment
`is a distinct term, and should be construed differently from amplification. Ariosa and Verinata argue
`that the enrichment term is equivalent to “amplifying” in claim 1, and therefore “without subjecting it
`to a foetal DNA enrichment step” should be construed as “prior to the amplification step of claim 1.”
`Natera contends that because claim 19 is not asserted in this case, it is not appropriate to construe this
`term.
`
`The Federal Circuit rejected the argument that amplifying means increasing the concentration,
`and found that “the specification discloses that ‘enrichment’ and ‘amplification’ are distinct.” Aria
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`Diagnostics, 2013 WL 4034379, at *5. It also found that the prosecution history was insufficient to
`constitute a clear disavowal of the broad language of the claim. Id. at *6. Therefore, the “enrichment
`step” must not refer to the amplification step of claim 1, but instead describes an action, enrichment,
`which has a distinct meaning from amplification.
`The Court disagrees with Natera, and finds that this claim should be construed because it is being
`asserted against at least one of the parties.
`“Foetal DNA enrichment step” is construed as “increasing the concentration of fetal DNA
`relative to the maternal DNA in the sample.”
`
`C.
`
`“Fetal/foetal”
`
`Claim Term
`
`“fetal” / “foetal”
`
`Sequenom’s
`Proposed
`Construction
` No construction
`needed –
`ordinary and
`customary
`meaning: “of or
`from a fetus”
`
`Ariosa’s
`Proposed
`Construction
`“of pregnancies
`from 7 to 40
`weeks of
`gestation”
`
`Natera/DDC’s
`Proposed
`Construction
`
`Verinata’s
`Proposed
`Construction
`
`Ariosa contends that “fetal” should be construed as “of pregnancies from 7 to 40 weeks of
`gestation” because the specification states that “[s]ex determination has successfully been performed
`on pregnancies from 7 to 40 weeks of gestation.”
`However, this statement in the specification does not rise to the level of clear disavowal of scope
`limiting “fetus” to 7 to 40 weeks of gestation, or a clear lexicography of the term. The statement merely
`remarks on the window for successful sex determination; it says nothing about the definition of a fetus
`or the possibilities of doing other prenatal tests within this time frame. Morever, this term has an
`ordinary and plain meaning that is known to both persons having ordinary skill in the art and lay
`persons. “The ordinary meaning of claim language may be readily apparent even to lay judges, and
`claim construction in such cases involves little more than the application of the widely accepted
`meaning of commonly understood words.” O2 Micro Int’l Ltd. v. Beyond Innovation Tech. Co., Ltd.,
`521 F.3d 1351, 1360 (Fed. Cir. 2008) (quotations omitted).
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`Petitioner Sequenom - Ex. 1016, p. 10
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`

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`Case3:12-cv-00132-SI Document133 Filed10/16/13 Page11 of 44
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`Therefore, the Court finds that this term does not require construction.
`
`D.
`
`“Determining the Concentration”
`
`Claim Term
`
`“determining the
`concentration”
`[Claim 13]
`
`Sequenom’s
`Proposed
`Construction
`No construction
`needed –
`ordinary and
`customary
`meaning:
`“determining the
`concentration of
`foetal nucleic
`acid in the
`maternal sample”
`
`Ariosa’s
`Proposed
`Construction
`Ariosa does not
`propose a
`construction, as
`Sequenom has
`not asserted
`claim 13 against
`Ariosa. Ariosa
`reserves its rights
`with respect to
`this term.
`
`Natera/DDC’s
`Proposed
`Construction
`Indefinite
`
`Verinata’s
`Proposed
`Construction
`
`In the joint claim construction brief Natera argues that this term is indefinite, but in its moving
`papers it makes no argument regarding this term. The Court finds that the term is not indefinite, but has
`an ordinary and customary meaning and no construction is needed.
`
`2.
`
`The ’017 and ’018 Patents (Verinata and Stanford)
`On February 15, 2011, the PTO issued the ’017 patent, entitled “Non-invasive Fetal Genetic
`Screening by Digital Analysis,” and on August 30, 2011, it issued the ’018 patent, entitled
`“Determination of Fetal Aneuploidies by Massively Parallel DNA Sequencing.” The ’018 patent is a
`continuation of the ’017 patent, and has a nearly identical specification. Stanford is the patent owner
`and Verinata is the exclusive licensee of these patents. They allege that Sequenom is infringing these
`patents. See Verinata I.
`The patents explain that “[s]ince aneuploidies do not present a mutational change in sequence,
`and are merely a change in the number of chromosomes, it has not been possible to detect them in a
`fetus without resorting to invasive techniques,” because researchers believed that determining whether
`a fetus was carrying an extra chromosome required distinguishing fetal DNA from maternal DNA. The
`’017 Patent, Abstract. However, the patent inventors discovered that “digital amplification allows the
`detection of aneuploidy using massively parallel amplification and detection methods.” Id. By using
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`For the Northern District of California
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`United States District Court
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`Petitioner Sequenom - Ex. 1016, p. 11
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`Case3:12-cv-00132-SI Document133 Filed10/16/13 Page12 of 44
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`sophisticated molecular counting techniques, the researchers could determine small under- or over-
`representations of a chromosome that would reveal fetal aneuploidy, without the need to distinguish
`between the maternal and fetal DNA. See id. 21:10-30.
`The relevant portion of the ’017 patent claims the following:
`Claim 17. A method for determination of the presence or absence of a fetal aneuploidy
`in a maternal tissue sample comprising fetal and maternal genomic DNA, wherein the
`method comprises:
`a) obtaining a mixture of fetal and maternal genomic DNA from said maternal tissue
`sample;
`b) distributing random fragments from the mixture of fetal and maternal genomic DNA
`of step a to provide reaction samples containing a single genomic DNA molecule or
`amplification products of a single genomic DNA molecule;
`c) conducting massively parallel DNA sequencing of the random fragments of
`genomic DNA in the reaction samples of step b) to determine the sequence of said
`random fragments;
`d) identifying the chromosomes to which the sequences obtained in step c) belong;
`e) analyzing the data of step d) to determine I) the number of copies of at least one
`first target chromosome in said mixture of fetal and maternal genomic DNA,
`wherein said at least one first target chromosome is presumed to be diploid in both
`the mother and the fetus, and ii) the number of copies of a second target chromosome
`in said mixture of fetal and maternal genomic DNA, wherein said second chromosome
`is suspected to be aneuploid in the fetus;
`f) conducting a statistical analysis that compares the number of copies of said at
`least one first target chromosome to the number of copies of said second target
`chromosome; and
`g) determining the presence or absence of a fetal aneuploidy from the results of the
`statistical analysis of step f).
`The ’017 Patent 35:11-25 (the construction of the highlighted terms is disputed by the parties). Also
`relevant, the ’018 patent claims the following:
`Claim 1. A method for determining presence or absence of fetal aneuploidy in a
`maternal tissue sample comprising fetal and maternal genomic DNA, wherein the
`method comprises:
`a. obtaining a mixture of fetal and maternal genomic DNA from said maternal tissue
`sample;
`b. conducting massively parallel DNA sequencing of DNA fragments randomly
`selected from the mixture of fetal and maternal genomic DNA of step a) to determine
`the sequence of said DNA fragments;
`c. identifying chromosomes to which the sequences obtained in step b) belong;
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`For the Northern District of California
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`United States District Court
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`Petitioner Sequenom - Ex. 1016, p. 12
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`Case3:12-cv-00132-SI Document133 Filed10/16/13 Page13 of 44
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`d. using the data of step c) to compare an amount of at least one first chromosome
`in said mixture of maternal and fetal genomic DNA to an amount of at least one
`second chromosome in said mixture of maternal and fetal genomic DNA, wherein
`said at least one first chromosome is presumed to be euploid in the fetus, wherein
`said at least one second chromosome is suspected to be aneuploid in the fetus,
`thereby determining the presence or absence of said fetal aneuploidy.
`Claim 3. The method of claim 1 wherein said massively parallel DNA sequencing
`comprises I) attaching said DNA fragments to a planar optically transparent surface; ii)
`conducting solid phase amplification of the attached DNA fragments to create a high
`density sequencing flow cell, and iii) sequencing of the amplified DNA fragments in
`the high density sequencing flow cell by a four-color DNA sequencing by synthesis
`process.
`The ’018 Patent 33:58-62, 34:49-57 (the construction of the highlighted terms is disputed by the parties).
`The parties agree that the terms “aneuploidy” in both the ’017 and the ’018 patent should be construed
`as “the occurrence of one or more extra or missing chromosomes.” They dispute the construction of the
`following terms in the ’017 and ’018 patents.
`
`A.
`
`“Massively Parallel DNA Sequencing”
`
`Claim Term
`
`“massively parallel DNA
`sequencing”
`[Claim 17 of the ’017 patent]
`
`“massively parallel DNA
`sequencing of the random
`fragments of genomic DNA”
`[Claim 17 of the ’017 patent]
`
`“massively parallel DNA
`sequencing”
`[Claim 1 of the ’018 patent]
`
`“massively parallel DNA
`sequencing of DNA fragments
`randomly selected”
`[Claim 1 of the ’018 patent]
`
`Verinata’s Proposed
`Construction
`“any sequencing method that
`allows for the acquisition of
`sequence information from
`multiple DNA fragments in
`parallel (e.g., the Illumina
`sequencing platform)”
`See above
`
`“any sequencing method that
`allows for the acquisition of
`sequence information from
`multiple DNA fragments in
`parallel (e.g., the Illumina
`sequencing platform)”
`See above
`
`13
`
`Sequenom’s Proposed
`Construction
`See below
`
`“massively parallel DNA
`sequencing of the random
`fragments of genomic DNA in
`each discrete reaction sample
`to detect the presence of the
`target sequence”
`See below
`
`“random, not targeted,
`massively parallel DNA
`sequencing”
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`For the Northern District of California
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`United States District Court
`
`Petitioner Sequenom - Ex. 1016, p. 13
`
`

`