Case 1:20-cv-01734-JLH Document 151 Filed 07/10/23 Page 1 of 16 PageID #: 12922
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`IN THE UNITED STATES DISTRICT COURT
`FOR THE DISTRICT OF DELAWARE
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`RAVGEN, INC.,
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`v.
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`Plaintiff,
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`ARIOSA DIAGNOSTICS, INC., ROCHE
`SEQUENCING SOLUTIONS, INC., ROCHE
`MOLECULAR SYSTEMS, INC., and
`FOUNDATION MEDICINE, INC.,
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`Defendants.
`______________________________________
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`RAVGEN, INC.,
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`v.
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`Plaintiff,
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`MYRIAD GENETICS, INC. and MYRIAD
`WOMEN’S HEALTH, INC.,
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`Defendants.
`______________________________________
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`RAVGEN, INC.,
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`Plaintiff,
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`V.
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`BIORA THERAPEUTICS, INC.,
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`Defendant.
`______________________________________
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`C.A. No. 20-1646-RGA-JLH
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`C.A. No. 20-1730-RGA-JLH
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`C.A. No. 20-1734-RGA-JLH
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`Case 1:20-cv-01734-JLH Document 151 Filed 07/10/23 Page 2 of 16 PageID #: 12923
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`REPORT AND RECOMMENDATION
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`Before the Court are the parties’ disputes over the construction of claim terms in United
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`States Patent Nos. 7,727,720 (the “ʼ720 patent”), and 7,332,277 (the “ʼ277 patent”). The Court
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`held a Markman hearing on May 31, 2023 (“Tr __.”), and announced its recommendations from
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`the bench on June 1, 2023. I recommend that the Court adopt the constructions set forth below.
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`Term
`“agent that [inhibits cell lysis to inhibit the
`lysis of cells / inhibits lysis of cells / impedes
`cell lysis] . . . wherein said agent is selected
`from the group consisting of membrane
`stabilizer, cross-linker, and cell
`lysis
`inhibitor” / “an agent that impedes [or
`inhibits] cell lysis” (ʼ277 patent, claims 8,
`55, and 81; ʼ720 patent, claim 1)
`“cell lysis inhibitor” (ʼ277 patent, claims 8,
`55, and 81; ʼ720 patent, claim 1)
`
`Court
`“a substance that inhibits the lysis of cells
`that is selected from the group consisting of
`membrane stabilizer, cross-linker, and cell
`lysis inhibitor, and does not include EDTA
`nor endogenous substances”
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`“chemical substance that prevents the lysis
`of cells or preserves the structural integrity
`of cells”
`“chemical substance that stabilizes the
`“membrane stabilizer” (ʼ277 patent, claims
`membranes of cells”
`8, 55, and 81; ʼ720 patent, claim 1)
`“free fetal DNA separated from non-nucleic
`“free fetal DNA isolated” / “isolating free
`acid” / “separating free fetal nucleic acid
`fetal nucleic acid” (ʼ277 patent, claims 55
`from non-nucleic acid”
`and 81)
`“non-cellular fraction” (ʼ720 patent, claim 1) “portion that is substantially free of cells”
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`1
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`4
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`5
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`I.
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`LEGAL STANDARDS
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`A.
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`Claim Construction
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`The purpose of the claim construction process is to “determin[e] the meaning and scope of
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`the patent claims asserted to be infringed.” Markman v. Westview Instruments, Inc., 52 F.3d 967,
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`976 (Fed. Cir. 1995) (en banc), aff’d, 517 U.S. 370 (1996). When the parties have an actual dispute
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`regarding the proper scope of claim terms, their dispute must be resolved by the judge, not the
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`jury. Id. at 979. The Court only needs to construe a claim term if there is a dispute over its
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`Case 1:20-cv-01734-JLH Document 151 Filed 07/10/23 Page 3 of 16 PageID #: 12924
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`meaning, and it only needs to be construed to the extent necessary to resolve the dispute. Vivid
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`Techs., Inc. v. Am. Sci. & Eng’g, Inc., 200 F.3d 795, 803 (Fed. Cir. 1999).
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`“[T]here is no magic formula or catechism for conducting claim construction.” Phillips v.
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`AWH Corp., 415 F.3d 1303, 1324 (Fed. Cir. 2005). But there are guiding principles. Id.
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`“The inquiry into how a person of ordinary skill in the art understands a claim term provides
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`an objective baseline from which to begin claim interpretation.” Id. at 1313. In some cases, the
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`ordinary meaning of a claim term, as understood by a person of ordinary skill in the art, is readily
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`apparent even to a lay person and requires “little more than the application of the widely accepted
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`meaning of commonly understood words.” Id. at 1314. Where the meaning is not readily apparent,
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`however, the court may look to “those sources available to the public that show what a person of
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`skill in the art would have understood disputed claim language to mean.” Innova/Pure Water, Inc.
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`v. Safari Water Filtration Sys., Inc., 381 F.3d 1111, 1116 (Fed. Cir. 2004). Those sources include
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`“the words of the claims themselves, the remainder of the specification, the prosecution history,
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`and extrinsic evidence concerning relevant scientific principles, the meaning of technical terms,
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`and the state of the art.” Id.
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`“The claims themselves provide substantial guidance as to the meaning of particular claim
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`terms.” Phillips, 415 F.3d at 1314. For example, “the context in which a term is used in the
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`asserted claim can be highly instructive.” Id. Considering other, unasserted, claims can also be
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`helpful. Id. “For example, the presence of a dependent claim that adds a particular limitation
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`gives rise to a presumption that the limitation in question is not present in the independent claim.”
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`Id. at 1314–15.
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`Case 1:20-cv-01734-JLH Document 151 Filed 07/10/23 Page 4 of 16 PageID #: 12925
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`In addition, the “claims must be read in view of the specification, of which they are a part.”
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`Id. at 1315 (quoting Vitronics Corp. v. Conceptronic, Inc., 90 F.3d 1576, 1582 (Fed. Cir. 1996)).
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`The specification “is always highly relevant to the claim construction analysis.” Id. (quoting
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`Vitronics, 90 F.3d at 1582). The specification may contain a special definition given to a claim
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`term by the patentee, in which case, the patentee’s lexicography governs. Id. at 1316. The
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`specification may also reveal an intentional disclaimer or disavowal of claim scope. Id. However,
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`“even when the specification describes only a single embodiment, the claims of the patent will not
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`be read restrictively unless the patentee has demonstrated a clear intention to limit the claim scope
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`using words or expressions of manifest exclusion or restriction.” Hill-Rom Servs., Inc. v. Stryker
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`Corp., 755 F.3d 1367, 1372 (Fed. Cir. 2014) (internal marks omitted).
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`Courts should also consider the patent’s prosecution history. Phillips, 415 F.3d at 1317.
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`It may inform “the meaning of the claim language by demonstrating how the inventor understood
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`the invention and whether the inventor limited the invention in the course of prosecution, making
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`the claim scope narrower than it would otherwise be.” Id. Statements made by a patentee or patent
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`owner during inter partes review may also be considered. Aylus Networks, Inc. v. Apple Inc., 856
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`F.3d 1353, 1362 (Fed. Cir. 2017).
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`In appropriate cases, courts may also consider extrinsic evidence, which “consists of all
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`evidence external to the patent and prosecution history, including expert and inventor testimony,
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`dictionaries, and learned treatises.” Markman, 52 F.3d at 980. For example, dictionaries,
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`especially technical dictionaries, can be helpful resources during claim construction by providing
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`insight into commonly accepted meanings of a term to those of skill in the art. Phillips, 415 F.3d
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`at 1318. Expert testimony can also be useful “to ensure that the court’s understanding of the
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`Case 1:20-cv-01734-JLH Document 151 Filed 07/10/23 Page 5 of 16 PageID #: 12926
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`technical aspects of the patent is consistent with that of a person of skill in the art, or to establish
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`that a particular term in the patent or the prior art has a particular meaning in the pertinent field.”
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`Id.; see also Teva Pharm. USA, Inc. v. Sandoz, Inc., 574 U.S. 318, 331–32 (2015).
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`B.
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`Indefiniteness
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`Section 112 of Title 35 imposes a definiteness requirement on patent claims. 35 U.S.C.
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`§ 112(b) (requiring that the claims “particularly point[] out and distinctly claim[] the subject matter
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`which the inventor . . . regards as the invention”). “The primary purpose of the definiteness
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`requirement is to ensure that the claims are written in such a way that they give notice to the public
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`of the extent of the legal protection afforded by the patent, so that interested members of the public,
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`e.g., competitors of the patent owner, can determine whether or not they infringe.” All Dental
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`Prodx, LLC v. Advantage Dental Prod., Inc., 309 F.3d 774, 779–80 (Fed. Cir. 2002).
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`“A patent is invalid for indefiniteness if its claims, read in light of the specification
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`delineating the patent, and the prosecution history, fail to inform, with reasonable certainty, those
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`skilled in the art about the scope of the invention.” Nautilus, Inc. v. Biosig Instruments, Inc., 572
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`U.S. 898, 901 (2014). Definiteness, like claim construction, should be assessed from the viewpoint
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`of a person of ordinary skill in the art at the time the patent was filed, and it should be considered
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`in view of the patent’s specification and prosecution history. Id. at 908.
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`The party asserting indefiniteness has the burden to prove it by clear and convincing
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`evidence. BASF Corp. v. Johnson Matthey Inc., 875 F.3d 1360, 1365 (Fed. Cir. 2017).
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`II.
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`THE COURT’S RULING
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`My Report and Recommendation regarding the disputed claim terms of the ʼ277 and ʼ720
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`patents was announced from the bench on June 1, 2023, as follows:
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`Case 1:20-cv-01734-JLH Document 151 Filed 07/10/23 Page 6 of 16 PageID #: 12927
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`I’m prepared to issue a report and recommendation on the
`claim construction disputes that were argued yesterday, May 31,
`2023. The parties resolved a number of the briefed disputes before
`the hearing yesterday. To the extent that the parties agree on those
`constructions or any other constructions, they should file a proposed
`order for Judge Andrews’s signature.
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`With respect to the terms that are still in dispute, I will not
`be issuing a separate written report and recommendation. I want to
`emphasize that, while I’m not issuing a separate written report and
`recommendation, we have followed a full and thorough process
`before making the recommendation that I’m about to state.
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`There was full briefing on each of the disputed terms. The
`parties submitted their briefing in accordance with my procedures,
`so each side had the opportunity to submit two briefs, and they were
`combined into one joint claim construction brief incorporating all
`arguments. The parties’ joint claim construction chart and brief also
`included numerous exhibits with intrinsic and extrinsic evidence,
`including expert declarations. My oral ruling will cite to the
`evidence cited by the parties that I conclude best supports my
`proposed constructions, but my failure to cite to other evidence
`provided by the parties does not mean that I ignored or failed to
`consider it.
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`I’m not going to read into the record my understanding of
`the general legal principles of claim construction. I set forth the
`legal standards in my opinion in 3Shape v. Align,1 and I incorporate
`that articulation by reference. Defendants have also argued that
`several of the disputed terms are indefinite. My understanding of
`the law of indefiniteness is also set forth in 3Shape v. Align.2
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`The first set of disputes comprise the majority of the parties’
`claim construction briefing. These disputes pertain to claims 8, 55,
`and 81 of the ʼ277 patent and claim 1 of the ʼ720 patent. Each of
`those four claims has an “agent” phrase with a similar format. Claim
`8 of the ʼ277 patent, for example, requires “an agent that inhibits
`cell lysis to inhibit the lysis of cells . . . wherein the agent is selected
`from a group consisting of membrane stabilizer, cross-linker and
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`1 3Shape A/S v. Align Tech., Inc., No. 18-886, 2020 WL 2188857, at *1–2 (D. Del. May
`6, 2020), report and recommendation adopted, 2020 WL 7695898 (D. Del. Dec. 28, 2020).
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` Id. at *2–3.
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`Case 1:20-cv-01734-JLH Document 151 Filed 07/10/23 Page 7 of 16 PageID #: 12928
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`cell lysis inhibitor.” Breaking that phrase down, it requires “an
`agent that inhibits cell lysis” where the agent is selected from a
`group of three things. The first is a membrane stabilizer. The
`second is a cross-linker. The third thing the agent that “inhibits the
`lysis of cells” can be is a cell lysis inhibitor.
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`Claim 55 has a similar format for the agent phrase. It
`requires “an agent that inhibits lysis of cells” where the agent is
`selected from the group of the same three things. Claim 81 is similar
`and requires “an agent that inhibits cell lysis” where the agent is
`selected from the group of three things. And finally, claim 1 of the
`ʼ720 patent similarly requires “an agent that impedes cell lysis”
`where the agent is selected from the group of three things.
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`The parties have a number of sub-disputes relating to this
`agent phrase. In the first sub-dispute, Defendants say that two of the
`three things on the list of possible agents—the terms “cell lysis
`inhibitor” and “membrane stabilizer”—are indefinite because they
`are not terms of art and because the specifications do not provide
`guidance for a POSITA to determine whether a particular substance
`qualifies as one of those types of agents. I find that, on this record,
`Defendants have failed to demonstrate by clear and convincing
`evidence that those terms are indefinite.
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`As for “membrane stabilizer,” Plaintiff says that a POSITA
`would understand it to mean “a chemical substance that stabilizes
`the membranes of cells.” I recommend adopting that construction.
`It is consistent with the claim language. It is also consistent with the
`extrinsic declaration of Plaintiff’s expert who says that the list of
`exemplary membrane stabilizers in the specification are chemical
`substances known to a POSITA as being capable of stabilizing the
`membrane of cells and that a POSITA reading that list would
`understand that a membrane stabilizer is a chemical substance that
`stabilizes the membrane of cells.3
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` also note that my conclusion that the term “membrane
`stabilizer” has not been shown to be indefinite is consistent with the
`conclusion reached by Judge Albright in the Ravgen v. Quest case
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` I
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`3 (No. 20-1646, D.I. 151, Ex. P3 ¶¶ 54–59.) All docket citations are to No. 20-1646
`unless otherwise noted.
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`Case 1:20-cv-01734-JLH Document 151 Filed 07/10/23 Page 8 of 16 PageID #: 12929
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`in Texas.4 While his determination is, of course, not binding on this
`Court, I do agree with his conclusion.
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`Turning to “cell lysis inhibitor,” Plaintiff’s brief proposed
`construing it as a chemical substance that preserves the structural
`integrity of cells. To the extent that Plaintiff’s proposed
`construction limits the mechanism by which the claimed agent has
`to inhibit cell lysis, I think that definition is too narrow. Nothing in
`the claim language suggests that the claimed cell lysis inhibitor has
`to inhibit cell lysis by a particular mechanism. Likewise, the
`specification does not suggest that the inhibition has to operate
`through a particular mechanism. Plaintiff’s expert points out that
`some of the items on the list of cell lysis inhibitors set forth at
`column 31, lines 4–21 of the ʼ277 patent, as well as Table XXIII
`beginning in column 226; and column 31, lines 43–54 of the ʼ720
`patent, as well as column 32 line 65 to column 33 line 28, and Table
`XXIII beginning in column 216, operate by preserving the structural
`integrity of the cells by cross linking.5 But that is not a reason to
`import a cross-linking limitation into the term “cell lysis inhibitor,”
`and doing so would not be consistent with another portion of the
`specification at column 91, lines 46–49 that says that “any agent that
`prevents the lysis of cells or increases the structural integrity of cells
`can be used.” In other words, the specification does not limit the
`cell lysis inhibitor to those agents that work by a particular
`mechanism.
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`During the hearing, I asked Plaintiff’s counsel if, consistent
`with that portion of the specification, the “cell lysis inhibitor” could
`instead be construed as a chemical substance that prevents the lysis
`of cells or preserves the structural integrity of cells. Counsel
`agreed.6 Accordingly, I agree with Plaintiff that Defendants haven’t
`demonstrated indefiniteness, and I recommend that “cell lysis
`inhibitor” be construed as “a chemical substance that prevents the
`lysis of cells or preserves the structural integrity of cells.”
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`Before I turn to the next sub-dispute, I’ll make a few
`comments about Defendants’ arguments on
`indefiniteness.
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`4 Ravgen Inc., v. Quest Diagnostics, Inc., No. 20-972, D.I. 65 at 5–6 (W.D. Tex. Oct. 5,
`2021) (D.I. 151, Ex. P14).
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` (D.I. 151, Ex. P3 ¶¶ 48–53.)
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` (Tr. 72:25–75:2.)
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`Case 1:20-cv-01734-JLH Document 151 Filed 07/10/23 Page 9 of 16 PageID #: 12930
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`Defendants recognize that a claim limitation defined by its function
`is not necessarily indefinite, but Defendants argue that a POSITA
`wouldn’t be able to determine if a given agent was a cell lysis
`inhibitor or a membrane stabilizer. I don’t take Defendants to be
`arguing that a POSITA couldn’t test an agent to see if it inhibits cell
`lysis or stabilizes cell membranes, and, in fact, the specification
`provides an example of such a test for inhibition of cell lysis.
`Instead, Defendants’ real point appears to be a that the claimed
`“membrane stabilizer” and “cell lysis inhibitor” are very broad and
`that a person of skill could not determine ex ante if a compound
`inhibits cell lysis under particular conditions. However, as the
`Federal Circuit explained in the BASF case, breadth is not
`indefiniteness.7 Moreover, as the Federal Circuit explained in the
`Nevro case, definiteness does not require that a potential infringer
`be able to determine ex ante if a particular act infringes the claims.8
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`Plaintiff’s expert opines that a POSITA reading the
`specifications and claims would have understood how to determine
`whether an agent is a membrane stabilizer or a cell lysis inhibitor.9
`Taking into account that extrinsic evidence and the intrinsic
`evidence, I find that, on this record, Defendants have failed to
`demonstrate that a POSITA could not determine whether a
`particular agent is a cell lysis inhibitor or a membrane stabilizer.
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` I
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` also reject Defendants’ argument that, in order for the
`claims to be definite, the specification or claims need to specify how
`much lysis inhibition or membrane stabilization is required. In a
`similar argument, some, but not all, of the Defendants argue that the
`terms “membrane stabilizer” and “cell lysis inhibitor” are terms of
`degree that fail to provide objective boundaries to a POSITA. I
`reject that argument because I disagree that the terms are terms of
`degree.
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`As Defendants point out, the list of items in the Markush
`group overlap; that is, a certain substance may be both, for example,
`a cell lysis inhibitor and a cross-linker. Moreover, the Court’s
`proposed construction of “cell lysis inhibitor” to include any
`chemical substance that inhibits cell lysis means that the “cell lysis
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`7 BASF Corp. v. Johnson Matthey Inc., 875 F.3d 1360, 1367 (Fed. Cir. 2017).
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` 8
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` Nevro Corp. v. Boston Scientific Corp., 955 F.3d 35, 40 (Fed. Cir. 2020).
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`9 (D.I. 151, Ex. P3 ¶¶ 42–59.)
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`inhibitor” species in the Markush group is essentially as broad as the
`genus “agent that inhibits cell lysis.” Defendants agreed at the
`hearing, however, that the mere overlap does not result in
`indefiniteness, and I agree with them on that.10 I’m not aware of
`any case that says that a Markush group expression is indefinite if
`its species overlap or even if a particular species is coextensive with
`its genus. It seems to me that if a POSITA could understand the
`bounds of the term regardless of the overlap, they are not
`indefinite.11
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`Defendants also point out that a particular agent might
`operate as a membrane stabilizer or cell lysis inhibitor under certain
`conditions but not others. I do not think that makes those terms
`indefinite. As I already noted, the definiteness inquiry does not
`require that a POSITA be able to determine ex ante if a particular
`agent falls within the scope of the claims, and I agree with Plaintiff
`that there’s no requirement in the claims or the intrinsic record that
`the agent must stabilize cell membranes in every possible chemical
`environment in order to qualify as a membrane stabilizer or cell lysis
`inhibitor.
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`Another sub-dispute has to do with the word “lysis.”
`Plaintiff’s proposed construction substitutes the word “rupture” in
`for “lysis.” Defendants say that’s inappropriate. Defendants’
`argument is hard to follow, but they seem to be arguing that even if
`cells ruptured, that would not necessarily increase the ratio of
`maternal to fetal DNA if a nuclear membrane in the cell is intact.
`Here is what I will say about this dispute: the extrinsic evidence does
`indeed suggest that “cell lysis” means the same thing as the “rupture
`of cells,” but I don’t understand at this point how replacing one word
`for another resolves any dispute for the parties or would clarify
`anything for the jury. The parties are free to bring this up at a later
`stage in the case if it appears that it’s going to have a material
`impact. For now, we’ll leave it as “lysis.”
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`The next set of sub-disputes have to do with Plaintiff’s
`proposal that the Court construe the agent phrase to exclude
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`10 (Tr. 41:23–42:5.)
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`11 (D.I. 151, Ex. P14 at 4–5 (citing Lexington Luminance LLC v. Amazon.com, Inc., 601
`F. App’x. 963, 968 (Fed. Cir. 2015) (“Definiteness involves more than an examination of the
`technical correctness of the use of a Markush expression that may have slipped past the
`examining process. It involves evaluation of the claim in light of the written description.”)).)
`10
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`Case 1:20-cv-01734-JLH Document 151 Filed 07/10/23 Page 11 of 16 PageID #: 12932
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`“chelators used as anticoagulants” and “endogenous substances.”
`I’ll take “endogenous substances” first. I agree with Plaintiff that
`the agent phrase is not met by “endogenous substances.” Construing
`the agent term to be met by something that’s already in the blood
`sample is contrary to the intrinsic evidence, and I don’t think the
`cited portions of the prosecution history support Defendants’
`argument. I also note that this same argument was rejected by Judge
`Albright in the Ravgen v. Natera case, and I agree with his reasoning
`and conclusion.12
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`The last sub-dispute is Plaintiff’s proposal to entirely
`exclude from the agent phrase “chelators used as anticoagulants.”
`On this dispute, I do not entirely agree with Plaintiff or with Judge
`Albright. Plaintiff’s argument goes like this: the specification
`contains an example experiment in which the test sample was treated
`with the cell lysis inhibitor formaldehyde in an EDTA tube, and the
`control sample was put in an EDTA tube. The control experiment
`was referred to in the example as having been analyzed “in the
`absence . . . of inhibitors of cell lysis.” (ʼ277 patent, 89:1–34.) This
`suggests that the patentee did not consider EDTA to be an inhibitor
`of cell lysis in this experiment. EDTA is not included in the
`exemplary lists of cell lysis inhibitors, membrane stabilizers, and
`cross-linkers in the specification of either patent.
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`During prosecution of the ʼ277 patent, the examiner rejected
`certain claims as anticipated by Lo, stating, “Lo et al. teach
`collecting maternal blood into a tube comprising EDTA (i.e. an
`agent that inhibits cell lysis.”13 The patentee responded in pertinent
`part:
`
`
`In addition to being improperly supported by
`documentary evidence, the assertion by the Office
`that EDTA is a cell lysis inhibitor is simply incorrect.
`Applicant asserts that EDTA is not an “agent that
`inhibits cell lysis.” Rather, EDTA is a well-known
`chelator of calcium and magnesium. EDTA is
`routinely added to blood during the blood collection
`process as an anticoagulant due to its ability to
`chelate calcium. In fact, EDTA is sometimes
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`12 Ravgen, Inc. v. Natera, Inc., No. 20-692, D.I. 176 at 6–8 (W.D. Tex. Nov. 8, 2021)
`(D.I. 151, Ex. P5).
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`13 (D.I. 151, Ex. P6 at 5.)
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`Case 1:20-cv-01734-JLH Document 151 Filed 07/10/23 Page 12 of 16 PageID #: 12933
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`included as an ingredient in cell lysis buffers. . . .
`EDTA is clearly referred to as a chelator in
`Applicant’s specification, not as a cell lysis inhibitor.
`. . . As shown in Example 4, discussed above, the
`addition of formalin, even in the presence of EDTA,
`to samples has a dramatic effect on the amount of
`free fetal DNA isolated from the samples. The fact
`that the addition of formalin can have such a
`dramatic effect on the percentage of free fetal DNA
`serves to demonstrate that formalin and EDTA have
`very different properties and cannot be equated to
`each other.
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`Since Lo et al. does not teach or suggest the use of an
`agent that inhibits cell lysis, Lo et al. does not teach
`and every element of [the rejected claims] . . . and
`since the Office’s assertion that EDTA is a cell lysis
`inhibitor is wholly unsupported by documentary
`evidence or reasoning, the rejection of [the claims] is
`improper.14
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`Plaintiff further points out that at various points during the
`prosecution of the asserted patents, the examiner treated references
`as not having disclosed the claimed agent notwithstanding the fact
`that when one goes back and looks at those references, they teach
`addition of the compounds EDTA and ACD, both of which are
`anticoagulant chelators. According to Plaintiff, this intrinsic
`evidence makes clear that anticoagulant chelators cannot be an agent
`that inhibits cell lysis or a cell lysis inhibitor. Judge Albright
`accepted that argument, as did the PTAB in one of the IPRs.15
`
`Defendants say that, at best, the intrinsic evidence shows that
`the patentee disavowed coverage of EDTA as a “cell lysis inhibitor”
`but that EDTA could still be an “agent that inhibits cell lysis” if it,
`in fact, performed that function in a particular product or reference.
`
` I
`
` agree with Plaintiff and the PTAB to the extent they
`conclude that the patentee disclaimed coverage of EDTA as a cell
`
`14 (D.I. 151, Ex. P7 at 33.)
`
`15 Ravgen, Inc. v. Natera, Inc., No. 20-692, D.I. 176 at 4–5 (D.I. 151, Ex. P5); Illumina,
`Inc. v. Ravgen, Inc., No. IPR2021-01271, D.I. 45 at 15–23 (P.T.A.B. Jan. 25, 2023) (D.I. 169,
`Ex. 2).
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`Case 1:20-cv-01734-JLH Document 151 Filed 07/10/23 Page 13 of 16 PageID #: 12934
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`lysis inhibitor and an agent that inhibits cell lysis. The patentee’s
`statements in the prosecution history demonstrate a clear disavowal
`of EDTA as a cell lysis inhibitor and an agent that inhibits cell lysis.
`
`But I disagree with Plaintiff and the PTAB to the extent that
`they conclude that the disclaimer extends more broadly to other
`anticoagulant chelators. The only clear disavowal in the prosecution
`history is the disavowal of EDTA.
`
` don’t think the specification supports Plaintiff’s argument
`that anticoagulant chelators cannot be the claimed agent. If
`anything, the specification suggests that anything can be the claimed
`agent if it has the effect of inhibiting cell lysis. For example, at
`column 91 lines 48–49, it says, “Any agent that prevents the lysis of
`cells or increases the structural integrity of cells can be used.” The
`specification is also clear that the claimed cell lysis inhibitor and
`membrane stabilizers are “not limited to” the chemicals listed in the
`specification. Plaintiff points out that EDTA is referred to in the
`specification as a chelator, but there is nothing in the specification
`that suggests that chelators in general cannot be the claimed agent.
`Rather, the specification is clear that anything that inhibits cell lysis
`can be the claimed agent.
`
`In sum, I conclude that the genus phrase should be construed
`as “a substance that inhibits the lysis of cells that is selected from
`the group consisting of membrane stabilizer, cross-linker, and cell
`lysis inhibitor, and does not include EDTA nor endogenous
`substances.”
`
`“Cell lysis inhibitor” should be construed as “chemical
`substance that prevents the lysis of cells or preserves the structural
`integrity of cells.” And “membrane stabilizer” should be construed
`as “chemical substance that stabilizes the membranes of cells.”
`
`The next set of disputed terms are the isolating terms. The
`parties briefed a dispute about the phrase “isolating free nucleic
`acid” which appears in claim 1 of the ʼ720 patent. I’m not sure that
`there was a real dispute there that needed resolution, and at the
`hearing, the parties appeared to have agreed. They’re going to meet
`and confer and propose a construction to the extent appropriate.
`
`However, there remains a dispute about the phrases “free
`fetal DNA isolated,” which appears in claim 55 of the ʼ277 patent;
`and “isolating free fetal nucleic acid,” which appears in claim 81 of
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`Case 1:20-cv-01734-JLH Document 151 Filed 07/10/23 Page 14 of 16 PageID #: 12935
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`the ʼ277 patent. The essence of the dispute between the parties is
`the question of what the fetal DNA has to be isolated or separated
`from. Defendants say the phrase requires the fetal DNA to be
`separated from non-nucleic acid materials and the maternal DNA.
`Plaintiff says the fetal DNA is separated from nonnucleic acid
`components, but it doesn’t have to be isolated from the maternal
`DNA.
`
`
`While the language of the claims, read in isolation, might
`suggest that the fetal DNA has to be separated from all of the rest of
`the components of a sample, it’s not unambiguous on that point.
`Certainly, the claim does not say that the fetal DNA has to be
`separated from the maternal DNA.
`
`Read in view of the specification, I am persuaded that the
`disputed phrases require separation of the fetal DNA from the non-
`nucleic acid components of the sample but that there is no
`requirement that it be separated from the maternal DNA. As
`Plaintiff points out, every example in the specification uses isolation
`techniques that do not separate the free fetal DNA from the free
`maternal DNA, so Defendants’ proposal would exclude every
`example in the specification.
`
`I’ve also examined the portions of the prosecution history
`cited by Defendants in support of their construction. However, I
`agree with Plaintiff that the prosecution history indicates that the
`word “fetal” was added to the claims not to specify that the fetal
`DNA needs to be isolated from the maternal DNA, but rather to
`indicate that the analysis is performed on a sample obtained from a
`pregnant female that contains fetal DNA.16
`
` I
`
` also note that my recommendation is consistent with the
`construction adopted by Judge Albright in the Ravgen v. Labcorp
`case.17 While his construction is, of course, not binding on the
`Court, I do agree with his conclusion.
`
`
`
`16 (D.I. 83, Ex. 8 at 10, 25.)
`
`17 Ravgen, Inc. v. Laboratory Corporation of Am. Holdings, No. 20-969, D.I. 62 at 3–6
`(W.D. Tex. Oct. 5, 2021) (D.I. 151, Ex. P19).
`
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`Case 1:20-cv-01734-JLH Document 151 Filed 07/10/23 Page 15 of 16 PageID #: 12936
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`For these reasons, I recommend adopting Plaintiff’s
`alternative proposal,18 which resolves the actual dispute between the
`parties. “Free fetal DNA isolated” should be construed as “free fetal
`DNA separated from non-nucleic acid” and “isolating free fetal
`nucleic acid” should be construed as “separating free fetal nucleic
`acid from non-nucleic acid.”
`
`The final remaining disputed term is “non-cellular fraction.”
`That term is found in claim 1 of the ʼ720 patent. Plaintiff’s proposed
`construction is “portion that is substantially free of cells.”
`Defendants propose “a fraction that does not contain cells.”
`
`The dispute between the parties is whether “non-cellular
`fraction” must be entirely free of cells or instead substantially free
`of cells.
`
` agree with Plaintiff. Starting with the language of the
`claims, Defendants say it supports them because the word “non-
`cellular” means “no cells.” I don’t think it’s as clear as Defendants
`suggest. The claims don’t say no cells. They say “non-cellular
`fraction,”