On September 2nd, the Patent Trial and Appeals Board (PTAB) entered judgment in an inter partes review styled Ariosa Diagnostics v. Isis Innovation Ltd. (IPR 2012-00022). The Board found that Ariosa demonstrated, by a preponderance of the evidence of record, that claims 1, 2, 4, 5, 8, 19, 20, 24, and 25 of U.S. Patent No. 6,258,540 are unpatentable under 35 U.S.C. § 102(b). But the Board found that Ariosa did not carry its burden of showing by a preponderance of the evidence that claims 3, 12, 13, 15, 18, 21, and 22 of the '540 patent were unpatentable under 35 US.C. § 103(a).
The claims under inter partes review are as follows:
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.
2. The method according to claim 1, wherein the foetal nucleic acid is amplified by the polymerase chain reaction.
3. The method according to claim 2, wherein at least one foetal sequence specific oligonucleotide primer is used in the amplification.
4. The method according to claim 1, wherein the foetal nucleic acid is detected by means of a sequence specific probe.
5. The method according to claim 1, wherein the presence of a foetal nucleic acid sequence from the Y chromosome is detected.
8. The method according to claim 1, wherein the presence of a foetal nucleic acid from a paternally-inherited non-Y chromosome is detected.
12. The method according to claim 5, for determining the sex of the foetus.
13. The method according to claim 5, which comprises determining the concentration of the foetal nucleic acid sequence in the maternal serum or plasma.
15. The method according to claim 13, for the detection of a maternal or foetal condition in which the level of foetal DNA in the maternal serum or plasma is higher or lower than normal.
18. The method according to claim 13, for detection of a foetal chromosomal aneuploidy.
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.
20. The method according to claim 19, wherein the fractional concentration of foetal DNA is at least about 0.39%.
21. A method of performing a prenatal diagnosis, which method comprises the steps of:
(i) providing a maternal blood sample;
(ii) separating the sample into a cellular and a non-cellular fraction;
(iii) detecting the presence of a nucleic acid of foetal origin in the non-cellular fraction according to the method of claim 1;
(iv) providing a diagnosis based on the presence and/or quantity and/or sequence of the foetal nucleic acid.
22. The method according to claim 21, wherein the non-cellular fraction as used in step (iii) is a plasma fraction.
24. A method for detecting a paternally inherited nucleic acid on a maternal blood sample, which method comprises:
removing all or substantially all nucleated and anucleated cell populations from the blood sample,
amplifying a paternally inherited nucleic acid from the remaining fluid and subjecting the amplified nucleic acid to a test for the Paternally inherited fetal nucleic acid.
25. A method for performing a prenatal diagnosis on a maternal blood sample, which method comprises
obtaining a non-cellular fraction of the blood sample
amplifying a paternally inherited nucleic acid from the non-cellular fraction
and performing nucleic acid analysis on the amplified nucleic acid to detect paternally inherited fetal nucleic acid.
(Italics indicating claims found unpatentable by the PTAB.)
The decision provided the following synopsis of the asserted grounds of unpatentability:
wherein the cited references are:
• Lo et al., Presence of Fetal DNA in Maternal Plasma and Serum, 350 LANCET 485–487 (1997).
• Simpson et al., Isolating Fetal Cells in Maternal Circulation for Prenatal Diagnosis, 14 PRENATAL DIAGNOSIS 1229–1242 (1994).
• Kazakov et al., Extracellular DNA in the Blood of Pregnant Women, 37(3) CYTOLOGY (TSITOLOGIA) 232–236 (1995).
• Bianchi et al., Fetal Cells in Maternal Blood: Determination of Purity and Yield by Quantitative Polymerase Chain Reaction, 171 AM. J. OBST.GYNECOL. 922–26 (1994).
• Schallhammer et al., Phenotypic Comparison of Natural Killer Cells from Peripheral Blood and from Early Pregnancy Decidua, 3 EARLYPREGNANCY: BIOLOGY AND MEDICINE 15–22 (1997).
The decision noted that Ariosa abandoned at oral argument its first two grounds of unpatentability set forth above.
Arriving at its bases for deciding the questions before it, the Board reiterated its decision (as set forth in its Decision on Petition) rejecting Isis's arguments that Ariosa lacked standing under § 315 to petition for inter partes review based on the litigation between the parties. Specifically, the Board addressed Isis's contention that "it 'is of no moment'" that Ariosa raised its validity challenge as an affirmative defense (in the face of Isis's infringement allegations prompted by Ariosa's declaratory judgment action for judgment of non-infringement). Isis also argued unsuccessfully that the exception under § 315(a)(3) does not apply because Isis (and its licensee, Sequenom) did not initiate the civil action. Finally, Isis argued (again unsuccessfully) that granting Ariosa's petition for inter partes review would "thwart the intent of Congress," inter alia, by permitting "patent owner harassment." For clarity, the Board set forth the precise question decided in granting Ariosa's petition:
[W]hether filing a Declaratory Judgment of non-infringement in District Court bars Ariosa from later filing a petition for Inter Partes Review under 35 U.S.C. § 315(a), and whether the express mention of a counterclaim of invalidity in 35 U.S.C. § 315(a)(3) mandates interpreting the statute such that raising an affirmative defense of invalidity in response to a compulsory counterclaim of infringement deprives Ariosa of standing to file for inter partes review.
The Board's decision to grant Ariosa's petition was based on its determination that the plain meaning of the statute, as interpreted by the definitions of "filing" and "a civil action" provided by the Federal Rules of Civil Procedure, is that the bar arises when a petitioner has filed a complaint prior to filing the inter partes review petition. The Board also distinguished between raising an affirmative defense and filing a counterclaim, based on its understanding of the differences defined by the Supreme Court in Altvater v. Freeman, 319 U.S. 359 (1943). In that case, the Court decided that a counterclaim is "justiciable" even in the face of a determination of non-infringement, while an affirmative defense of invalidity under similar circumstances would be to "decide a hypothetical case." Citing Cardinal Chem. Co. v. Morton Int'l, Inc., 508 U.S. 83 (1993), the Board decided that "it is clear []that there is a fundamental difference between an affirmative defense of invalidity and a counterclaim of invalidity," and thus that the declaratory judgment of non-infringement by Ariosa in this case did not fall within the activities the statute provides would bar the grant of the inter partes review petition.
The Board also rejected Isis's contention that § 315(b) barred grant of the petition because Isis had filed its infringement lawsuit more than a year before filing the inter partes review petition, because the infringement complaint had been dismissed without prejudice, citing the Board's prior decision to this effect in Macauto U.S.A. v. BOS GmbH & KG, Case IPR2012-00004 (PTAB January 24, 2013).
In the last of the procedural issues discussed in the decision, the Board rejected Isis's contention that granting Ariosa's Motion for Joinder (of two separate inter partes actions against different combinations of claims) was improper (despite the statutory language being limited to joinder of parties; § 315(c)) based on its practice in prior proceedings permitting such joinder, including Microsoft Corp. v. Proxycann, Inc., Case IPR2013-00109 (PTAB February 25, 2013), and Samsung Elecs. Co., Ltd. v. Virginia Innovation Scis., Inc., Case IPR2014-00557 (PTAB June 13,2014). The Board found no prohibition of issue joinder in either the statutory language or the legislative history, and relied on its rules (37 CFR § 42.1(b)) implementing § 316, specifying that "[t]he rules are to be construed so as to ensure the just, speedy, and inexpensive resolution of a proceeding."
Turning to the merits of Ariosa's invalidity contentions, the Board construed the claim term "detecting." In doing so, the Board made the following claim construction determination applying the "broadest reasonable interpretation" standard under 37 C.F.R. § 42.100(b):
"detecting" means that the amplified DNA was detected, but not that such DNA be identified as being of paternal or fetal origin.
This construction, according to the Board, is consistent with the construction used by Isis's expert at trial, and further that in the context of the claims Isis could have limited what was detected to paternal and fetal DNA by stating that "only" this DNA was detected (but, says the Board, "they chose not to do so," implying a decision point that there is no evidence Isis ever encountered). While the Board relies on claim construction canons (such as not reading limitations from the specification into the claims), it is incongruous that the Board rendered this construction decision (which is dispositive; see below) in interpreting the scope and meaning of claims specifically directed towards detecting paternal or fetal DNA in pregnant female blood.
With this construction established, the decision turned to the cited references. Regarding the Kazkov reference, asserted against claims 1, 2, 4, 5, 8, 19, 20, 24 and 25, the Board found that the practice of the methods disclosed in the reference inherently anticipated these claims, because amplification of DNA from maternal blood would necessarily detect "paternally inherited nucleic acid of fetal origin." Specifically, the Board found that the reference taught that: 1) extracellular DNA is present in human blood; 2) the amount of this DNA increases with pregnancy; 3) this DNA was detected using PCR; 4) the amplified DNA was detected (using gel electrophoresis); and 5) the primers Kazakov used would have detected paternal DNA (insofar as the primers amplified sequences present (albeit not exclusively) on the Y chromosome).
Under the Board's construction, "Kazakov discloses the same method of claim 1." The Board stated that "all that is required by the amplification step of claim 1 is a step of amplifying nucleic acid from a serum or plasma sample from a pregnant female, such as by PCR, as such amplified nucleic acid would necessarily include fetal nucleic acid, and the fetal nucleic acid necessarily includes paternally inherited nucleic acid," so long as "the detecting step does not require that the detected nucleic acid specifically be identified as being inherited from the father or even as being from the fetus, only that it be identified as containing some level of nucleic acid, which would include, necessarily, nucleic acid from the fetus that was inherited from the father." The Board further reasoned that:
[I]f the ordinary artisan were to follow the teachings of Kazakov, and perform PCR on the serum obtained from the blood obtained from a pregnant female, that blood would inherently contain paternally inherited fetal nucleic acid. That nucleic acid would be amplified and detected by the experiments of Kazakov as such a result is necessarily inherent. That is, the amplification and detection of paternally inherited fetal nucleic acid would be a new benefit of a known process.
The Board further "credited" the testimony of Ariosa's expert, that the methods disclosed in Kazakov were all "conventional," although there is no discussion on the significance of these findings to the Board's decision. And Isis's arguments that the possibility that fetal or paternal DNA would not be detected received no traction with the Board in refuting its inherent anticipation determination (which is not surprising, because the Board's error was in claim construction not the application of the facts to the incorrectly construed claims).
Having made this determination regarding claim 1, the Board did not find (and in some cases Isis did not provide) any basis for the same reasoning not to be applied to claims 2, 4, 5, 8, 19, 20, 24, and 25, and thus found these claims to also be inherently anticipated by the Kazakov reference.
Regarding obviousness, the Board held that Ariosa had not borne its burden of establishing invalidity by a preponderance of the evidence. Limiting its considerations to the combination of the Kazakov and Simpson references, the Board found that the Simpson reference taught detection of fetal cells, not fetal cell-derived DNA in maternal whole blood, and that the art taught that detecting fetal cells in maternal blood was "a rare occurrence." Under these circumstances, the Board found that:
[T]he ordinary artisan would not have used the serum sample of Kazakov, which is a cell-free sample, for the whole blood sample of Simpson, which contains the cellular fraction, for the analysis of fetal DNA as taught by Simpson. The ordinary artisan would not have had a reasonable expectation that the fetal DNA would have been present in maternal serum in sufficient quantities for detection using amplification methods such as PCR given the understanding in the art that fetal cells were a rare occurrence in maternal blood. Moreover, Kazakov's lack of teaching that the increase in extracellular DNA in the serum of pregnant females is due to the presence of cell-free fetal DNA in the serum further supports that conclusion.
Ironically, the Board's decision on obviousness relies on the failure of the art to recognize that fetal or paternal DNA could be detected in maternal blood, a distinction that the Board did not credit in its claim construction leading to its contrary decision regarding (inherent) anticipation by the Kazakov reference.
The Board also rejected Ariosa's obviousness contentions based in the combination of the Kazakov, Simpson, Schallhammer (earlier determined by the Board to be cumulative over the teachings of the Simpson reference) and Bianchi references (wherein Bianchi taught Y-chromosome specific primers), based on the same lack of expectation that fetal cells (or their DNA) would be expected by the skilled artisan to be present in maternal blood.
The Board also denied Isis's motion to amend its claims, once again rendering a decision that contradicts the rationale for construing claims according to the broadest reasonable interpretation of its terms (i.e., that when before the PTO the patentee can amend her claims). The proposed amended claims are as follows, and were proposed to overcome the Board's broad construction of the term "detected" in the patented claims:
28. 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 by determining that the paternally inherited fetal nucleic acid contains a sequence not possessed by the pregnant female.
31. 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 by determining that the paternally inherited nucleic acid of fetal origin contains a sequence not possessed by the pregnant female,
and
determining fetal sex, fetal chromosomal aneuploidy, fetal mutation, fetal RhD status, or fetal paternally-inherited DNA polymorphism.
In a Kafka-esque fashion, the Board denied the motion because the patentee is under a burden of showing she is "entitled" to the "relief" of amending claims, and the burden imposed is to establish that the claims are patentable under all sections of the Patent Act. Even though inter partes review is limited to the issues of anticipation and obviousness based on prior art, the Board permits a challenge on the patentability of amended claims on all the statutory sections. Here, citing the District Court's decision (and in the face of the pending Federal Circuit appeal), the Board determined that Isis had failed to carry its burden of showing that the proposed amended claims are patent-eligible under § 101.
PTAB recognized that claims 1, 2, 4, 5, 8, 19–22, 24, and 25 of the '540 patent were declared invalid in Ariosa Diagnostics v. Sequenom. With the exception of claim 21, this outcome suggests that Ariosa could have invalidated the claims in the district court under § 102(b) and done much less violence to the patent system in doing so. It also raises the possibility that Sequenom may move the Federal Circuit to vacate the District Court's judgment based on § 101 in view of the Office's determination that the claims are invalid under § 102(b).
The Board's decision provides Isis with another opportunity to appeal to the Federal Circuit, this time on the PTAB's decision invalidating these claims. Assuming that the Court reverses the District Court on the patent eligibility issue, the Board has provided for review by the Court with issues of claim construction as well as procedural questions decided by the Board in instituting the petition in the first place.
