Bio-Rad Laboratories, Inc.

Patent Trials and Appeals Board

Jul 28, 2021

IPR2020-00088 (P.T.A.B. Jul. 28, 2021)

Trials@uspto.gov Paper 41
571-272-7822 Entered: July 28, 2021

UNITED STATES PATENT AND TRADEMARK OFFICE

BEFORE THE PATENT TRIAL AND APPEAL BOARD

10X GENOMICS, INC.,
Petitioner,
v.
BIO-RAD LABORATORIES, INC.,
Patent Owner.

IPR2020-00088
Patent 9,896,722 B2

Before CHRISTOPHER M. KAISER, KIMBERLY MCGRAW, and
ELIZABETH M. ROESEL, Administrative Patent Judges.
Opinion for the Board filed by Administrative Patent Judge ROESEL.
Opinion Concurring filed by Administrative Patent Judge McGRAW.
ROESEL, Administrative Patent Judge.
DECISION
Denying Petitioner’s Request for Rehearing of Final Written Decision
37 C.F.R. § 42.71(d)
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Patent 9,896,722 B2
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I. BACKGROUND
10X Genomics, Inc. (“Petitioner”) timely filed a request for rehearing
(Paper 40, “Reh’g Req.” or “Request”) of our Final Decision (Paper 39,
“Dec.”) finding some claims of U.S. Patent No. 9,896,722 B2 (“the ’722
Patent,” Ex. 1001) unpatentable.
For the reasons that follow, we deny Petitioner’s request for rehearing.
II. STANDARD OF REVIEW
As it relates to a request for rehearing of a Board decision, in pertinent
part, 37 C.F.R. § 42.71(d) states:
The burden of showing a decision should be modified lies with
the party challenging the decision. The request must specifically
identify all matters the party believes the Board misapprehended
or overlooked, and the place where each matter was previously
addressed in a motion, an opposition, or a reply.
Thus, a request for rehearing is not an opportunity to present new arguments
or evidence or merely to disagree with the panel’s assessment of the
arguments or weighing of the evidence.
III. ANALYSIS
Petitioner challenges our determination that Petitioner did not show
by a preponderance of the evidence that dependent claims 15–17 of the ’722
Patent are unpatentable.
Claim 15 depends from claim 14 and recites: “after the separation
step, further comprising placing the droplets onto a second continuous phase
carrier fluid.” Ex. 1001, 89:4–6. Claim 16 depends from claim 15 and
recites: “wherein the second continuous phase carrier fluid comprises a de-
stabilizing surfactant.” Id. at 89:7–8. Claim 17 depends from claim 15 and
recites: “after the placing step, further comprising destabilizing the
droplets.” Id. at 89:9–10.
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A. The Petition
The Petition’s analysis of claims 15–17 is reproduced below.
Ismagilov describes reactions for creating compounds for
later use, e.g., “synthesis of macroscopic quantities of chemical
and biological compounds, e.g., the destruction of chemical
warfare agents and pharmaceuticals synthesis.” Id., 1:24–28;
see also id., 3:36–41 (“polymerizations, crystallizations
(including small molecule and proteins), nanoparticle synthesis,
formation of unstable intermediates, enzyme-catalyzed reactions
and assays, protein binding, etc.”), 50:51–52; Ismagilov 119,
¶ 117 (reaction types not limited, listing examples). These uses
would require breaking the emulsions to aggregate sufficient
quantities of reaction product.
Ismagilov also discloses what Ismagilov described as
“[f]luorosurfactants” with “biocompatibility in blood substitutes
and other biomedical applications” and that were “resistant to
protein adsorption.” To obtain the contents of droplets made
using this preferred surfactant, The POSA would look to methods
of demulsification, or breaking emulsions. To break an
emulsion, it was well-known that chemical demulsifers [sic],
including surfactants, could be used, as described in section VI.
A POSA would look to methods of demulsification. Per section
VI, 722 Patent. A POSA also knew that perfluorooctanol could
be used for droplet merging. See 21:16–29; 61:19–21 (using
“1H,1H,2H2H-perfluorooctanol.”). For example, Ismagilov
disclosed perflorooctanol [sic] “surfactant” as 10% of the carrier
fluid solution for droplet merging. Ismagilov, (“1H,1H,2H2H-
perfluorooctanol”); Ex. 1001, 48:25–28 (“1H,1H,2H,2H-
Perfluoro-1-octanol”). A second continuous carrier with a
destabilizing surfactant was obvious, including because it was
obvious to perform merging of multiple droplets (i.e., droplet
breaking).
It would be obvious to add this surfactant to stable droplets
in a tube or other vessel to de-emulsify and aggregate reaction
product, meeting Bio-Rad’s construction of continuous phase
carrier fluid. Fair, ¶¶ 190–195. . . .
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As above, it would have been obvious to add a second
continuous phase carrier fluid with a destabilizing surfactant
(perfluorooctanol) to destabilize droplets. Fair, ¶¶ 190–195.
Pet. 51–53 (heading quoting claims 16, 17 omitted; citing Ex. 1001;
Ex. 1004 (“Ismagilov 091”); Ex. 1005 (“Ismagilov 119”); Ex. 1008 (Fair
Declaration)). Cross-referenced section VI of the Petition included a
discussion of using surfactants as demulsifiers. Pet. 11–12 (citing
Exs. 1009,1 1057,2 1058,3 10594).
B. The Final Decision’s Analysis of Claims 15–17
The Final Decision’s analysis of claims 15–17 is reproduced below.
Petitioner’s contentions for claims 15–17 are not sufficiently
supported by the teachings of Ismagilov 091. Petitioner cites the
’722 Patent’s disclosure of a 1H,1H,2H,2H-perfluoro-1-octanol
as a de-stabilizing surfactant contained in a second continuous
phase carrier fluid (Ex. 1001, 48:25–28) and contends that
Ismagilov 091 discloses the same surfactant “for droplet
merging.” Pet. 52 (Ex. 1004, 21:16–29, 61:19–21). Not true.
Ismagilov 091 teaches perfluorooctanol as a surfactant to
stabilize droplets in channels, not to destabilize or merge
droplets. Ex. 1004, 21:7–35. More specifically, Ismagilov 091
teaches that “the plugs remain stable and do not leave behind any
residue as they are transported through the channels” when “the
surface tension at a plug fluid/channel wall interface . . . is set
higher than the surface tension at a plug fluid/carrier-fluid
interface . . . with a surfactant such as 10% 1H,1H,2H,2H-
perfluorooctanol.” Id. at 21:11–22. Petitioner does not direct us
to any teaching or suggestion in Ismagilov 091 that a surfactant,

1 Excerpts of Encyclopedic Handbook of Emulsion Technology (2001).
2 Excerpts of Emulsions Theory and Practice, 3rd Ed. (2001).
3 J. Wu, et al., Effect of EO and PO positions in nonionic surfactants on
surfactant properties and demulsification performance, Colloids and
Surfaces A: Physicochem. Eng. Aspects 252, 79–85 (2005).
4 Viovy et al., WO 2006/027757, published Mar. 16, 2006.
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such as perfluorooctanol, can be used to destabilize or merge
droplets.
Even if destabilizing surfactants were known in the art,
Petitioner does not direct us to evidence sufficient to establish
that it would have been obvious to place the droplets onto a
second continuous phase carrier fluid comprising a destabilizing
surfactant to destabilize the droplets, as recited in claims 15–17.
Dr. Fair’s testimony (Ex. 1008 ¶¶ 190–193) is essentially the
same as the Petition (Pet. 51–52) and suffers from the same
deficiencies.
Dec. 62–63.
Petitioner is correct that our conclusion with respect to claims 15–17
is based on two subsidiary findings: (i) that “Ismagilov 091 teaches
perfluorooctanol as a surfactant to stabilize droplets in channels, not to
destabilize or merge droplets” and that “Petitioner does not direct us to any
teaching or suggestion in Ismagilov 091 that a surfactant, such as
perfluorooctanol, can be used to destabilize or merge droplets,” and (ii) that
Even if destabilizing surfactants were known in the art, Petitioner
does not direct us to evidence sufficient to establish that it would
have been obvious to place the droplets onto a second continuous
phase carrier fluid comprising a destabilizing surfactant to
destabilize the droplets, as recited in claims 15–17.
Reh’g Req. 3; Dec. 62–63. Each of these findings provides a sufficient
independent basis for our determination as to claims 15–17.
As discussed below, Petitioner does not show that either of these
findings misapprehended or overlooked the teachings of Ismagilov 091 or
the arguments and evidence presented in the Petition.
C. Petitioner’s Attempt to Re-argue its Case for Unpatentability of
Claims 15–17 is Not Persuasive
The Request reargues Petitioner’s case for unpatentability of claims
15–17 in a way that was not presented in the Petition. Compare Reh’g Req.
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4–8, with Pet. 11–12, 51–53. For example, the Request relies on Exhibits
1009, 1057, 1058, and 1059 (Reh’g Req. 5), which were discussed in a
section of the Petition addressing the state of the art, but were not
specifically relied upon when addressing unpatentability of claims 15–17.
Pet. 11–12 (citing Exs. 1009, 1057, 1058, 1059); see also Pet. 51–53
(addressing claims 15–17).
In the Request, Petitioner argues that it was known in the art to “add[]
a liquid comprising a destabilizing surfactant to a test tube containing an
emulsion of water droplets in oil (like that produced by Ismagilov) in order
to destabilize (that is, break) the droplet emulsion.” Reh’g Req. 5 (citing
Pet. 11–13; Ex. 1008 ¶ 62; Exs. 1009, 1057, 1058, 1059). That argument
expands upon the argument in the Petition, which asserted that “[b]reaking,
merging, and coalescing droplets with surfactants was well known” (Pet. 12)
and “[i]t would be obvious to add this surfactant [1H, 1H, 2H, 2H-
perfluorooctanol (“PFO”)] to stable droplets in a tube or other vessel to de-
emulsify and aggregate reaction product” (Pet. 52).
Petitioner’s arguments about Exhibits 1009, 1057, 1058, and 1059 in
the Request differ from Petitioner’s characterization of this evidence in the
Petition. According to the Petition, Exhibit 1009 discloses “chemical
‘demulsification’ in petroleum-based emulsions” and includes “a table of
chemical demulsifiers used with crude oil.” Pet. 11 (citing Ex. 1009, 541,
564, 579, 580, Table 4). According to the Petition, Exhibit 1057 discusses
chemical demulsification using surface-active agents and breaking water/oil
emulsions, such as “industrially important oil-field emulsions.” Pet. 11–12
(citing Ex. 1057, 289, 292). According to the Petition, Exhibit 1058
discloses “demulsifiers” as a “means of breaking water-in-oil emulsions that
occur in industrial processes.” Pet. 12 (quoting Ex. 1058, Abstract).
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According to the Petition, Exhibit 1059 (“Viovy”) discloses that a “side
channel” can be configured to deliver a “solution containing a surfactant”
and that droplet coalescence is favored when the surface tension between
water droplets and the surrounding oil-based fluid is reduced by the presence
of a surfactant, such as PFO. Pet. 12 (citing Ex. 1059, 10–12).
Petitioner does not direct us to teachings in Exhibits 1009, 1057,
1058, and 1059 sufficient to support its contention that it would have been
obvious to add PFO as a destabilizing surfactant to a test tube containing an
emulsion of water droplets in oil, like that produced by Ismagilov 091, in
order to destabilize or break the droplet emulsion in order to recover the
sample contained in the droplets. The cited portions of Exhibits 1009, 1057,
and 1058 relate to demulsifying petroleum-based emulsions, and Petitioner
does not assert that any of the chemical demulsifiers disclosed in these
references would have been used to break a droplet emulsion like that
produced by Ismagilov 091. Viovy discloses microfluidic devices and
methods for coalescing a pair of droplets in a microchannel and discloses
that a surfactant may be chosen to favor the formation of oil-in-water
emulsions or to favor droplet coalescence. Ex. 1059, 5–6, 10–11. Viovy
does not disclose adding PFO as a surfactant to break an emulsion of
droplets in order to collect the contents of the droplets, and Petitioner did not
explain sufficiently how the teachings of Viovy would have led a POSITA
to use PFO in the manner asserted in the Petition. Pet. 12 (discussing
Viovy); Pet. 52 (asserting that “[i]t would have been obvious to add [PFO]
to stable droplets in a tube or other vessel to de-emulsify and aggregate
reaction product”). Petitioner had the burden to provide an evidence-
supported explanation showing that a POSITA would have understood the
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prior art as suggesting the subject matter of claims 15–17, and Petitioner
failed to do so, either in the Petition or in the Request.
The Request contains several inaccurate assertions about
Exhibit 1009. First, contrary to the Request, Dr. Fair did not rely on Exhibit
1009’s disclosure of chemical demulsifiers. Compare Reh’g Req. 5 (citing
“Fair [Ex. 1008] ¶ 62” as discussing Ex. 1009), with Ex. 1008 ¶ 62 (no
mention of Exhibit 1009). Second, Petitioner asserts that Exhibit 1009
“list[s] ‘fatty alcohols’ in Table 4 as demulsifiers used at least as early as
1935.” Reh’g Req. 5–6. Petitioner’s assertion misstates Table 4 of Exhibit
1009, which discloses that “[e]thoxylates of . . . fatty alcohols” (not fatty
alcohols themselves) were used as demulsifiers of crude oil emulsions up to
1935. Ex. 1009, 580.5 This is confirmed by the text of Exhibit 1009 that
precedes Table 4, where the same ethoxylates as listed in Table 4 are
disclosed as examples of nonionic surfactants useful as chemical
demulsifiers.6 Third, the Request asserts that “[f]atty alcohol ethers (that is,
chemicals like PFO that have a hydrocarbon tail and an alcohol head group)
have been used by those in the art as destabilizing surfactants to break water-

5 To be consistent with the Petition, we cite the original pagination of
Exhibit 1009. The Request cites the exhibit-stamped pagination, which in
this instance is pages 127–128.
6 Exhibit 1009 discloses: “Chemicals used as demulsifiers may be simple
surfactants. These may be cationic . . . ; anionic . . . ; nonionic . . . ; and
zwitterionic . . . .” Ex. 1009, 579. Examples of each type of surfactant are
disclosed. Id. The first three examples of “nonionic” surfactants are: “fatty
alcohol ethers [CH3(CH2)10CH2O(C2H4O)nH], fatty esters
[(CH3(CH2)10COO (C2H4O)nH], [and] alkyl phenol ethers [R-Ph-O-
(C2H4O)nH].” Id. These are the same three chemicals that Table 4 lists as
having been used as demulsifiers of crude oil emulsions up to 1935:
“Ethoxylates of fatty acids, fatty alcohols, and alkylphenols.” Id. at 580.
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in-oil emulsions since at least 1935.” Reh’g Req. 5 (citing Pet. 11; Ex. 1008
¶ 62; Ex. 1009, 579–580). That assertion is mere attorney argument,
supported neither by Dr. Fair’s testimony nor by Exhibit 1009.
As already mentioned, Dr. Fair did not rely on Exhibit 1009’s
disclosure of chemical demulsifiers. Exhibit 1009 discloses that fatty
alcohol ethers such as CH3(CH2)10CH2O(C2H4O)nH (an ethoxylated fatty
alcohol) were used as chemical demulsifiers of crude oil emulsions up to
1935. Ex. 1009, 579–580. But there is no support in Petitioner’s citations
for its assertion that PFO is “like” the fatty alcohol ethers that Exhibit 1009
discloses were used as chemical demulsifiers of crude oil emulsions. On the
contrary, Dr. Fair characterizes PFO as “a fluorinated carbon chain with an
alcohol” and a “fatty alcohol,” not a fatty alcohol ether or fatty alcohol
ethoxylate. Ex. 1008 ¶ 62. Even if PFO and fatty alcohol ethoxylates both
have a hydrocarbon tail and an alcohol head group, that is not enough to
prove that PFO was known in the art as a destabilizing surfactant to break
water-in-oil emulsions, as argued by Petitioner. Reh’g Req. 5. Petitioner’s
case against claims 15–17 hinged on its assertion that it would have been
obvious to use PFO to break an emulsion of droplets, but Petitioner did not
bring forward evidence to sufficient to meets its burden to show that PFO
was known for this use prior to the effective date of the ’722 Patent.7
Next, the Request argues that “PFO was known by those of ordinary
skill in the art to be a destabilizing surfactant (a fatty alcohol) useful for
breaking water-in-oil emulsions when a fluorinated oil is used (e.g., as
taught by Ismagilov).” Reh’g Req. 6 (citing Pet. 11, 52; Ex. 1008 ¶¶ 62,

7 As discussed below, we are not persuaded that Ismagilov 091 supports
Petitioner’s contention that PFO was known for emulsion-breaking.
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192, 193; Ex. 1004, 61:19–21, 64:8–65:15; Ex. 1059, 11–12). As support
for that argument, Petitioner relies on portions of Ismagilov 091 and Viovy
that were not discussed in the Petition or the Fair Declaration. Although
Petitioner and Dr. Fair cited Viovy’s disclosure of PFO (Pet. 12 (citing
Ex. 1059, 12); Ex. 1008 ¶ 62 (same)), they did not rely on Viovy to support
an argument that PFO was useful for breaking water-in-oil emulsions when a
fluorinated oil is used.
In any event, we are not persuaded that Viovy supports Petitioner’s
assertion. Like Ismagilov 091, Viovy is concerned with “reducing the risk
of interaction of the packets [droplets] with the wall of the microchannel in
the presence of the embedding fluid [carrier fluid].” Compare Ex. 1059,
11:19–21, with Ex. 1004, 21:7–35 (disclosing that a fluorinated surfactant is
used to “allow[] the formation of plugs that do not stick to the channel
walls”). Viovy teaches to reduce the risk of droplets interacting with the
microchannel walls in the same way as Ismagilov 091: by making the
surface tension between the droplets and the microchannel wall higher than
the surface tension between the droplets and the carrier fluid. Ex. 1004,
21:16–35 (“the surface tension at a plug fluid/channel wall interface . . . is
set higher than the surface tension at a plug fluid/carrier-fluid interface . . .
with a surfactant”); Ex. 1059, 11:23–32 (“the interfacial tension between the
droplet and the microchannel wall is made larger than the interfacial tension
between the droplet and the surrounding fluid, by treating the microchannel
wall and/or by including in the droplet and/or in the fluid additives. . . . The
surface tension between water and hydrogenated oil-based fluids can be
decreased by the presence of surface-active molecules.”). Like
Ismagilov 091, Viovy teaches that PFO can be used as a surfactant with a
fluorinated carrier fluid to reduce the surface tension at the droplet-carrier
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fluid interface. Ex. 1004, 21:7–35; Ex. 1059, 11:31–12:6. Contrary to
Petitioner’s assertion, Viovy does not teach PFO for breaking a droplet
emulsion, and Petitioner does explain sufficiently how the teachings of
Viovy would have led a POSITA to use PFO in the manner asserted in the
Petition.
The Request also relies on Example 4 of Ismagilov 091, asserting that
the droplet merging experiments were performed using a 10:1 mixture of
perfluorodecaline (“PFD”) and PFO. Reh’g Req. 6 (citing (Ex. 1004,
64:8–65:15)). Neither the Petition nor the Fair Declaration relied on
Example 4 of Ismagilov 091. Although the Petition and Dr. Fair asserted
that a “POSA also knew that perfluorooctanol could be used for droplet
merging” (Pet. 52 (citing Ex. 1004, 21:16–29, 61:19–21); Ex. 1008 ¶ 192
(same)), that assertion is not supported by Ismagilov 091, which provides no
teaching or suggestion that PFO can be used to destabilize or merge droplets.
Ismagilov 091 teaches forming droplets using a mixture of PFD and PFO as
the carrier fluid and further teaches that PFO prevents the droplets from
sticking to the channel walls. Ex. 1004, 21:16–29, 62:9–20, Fig. 26. As
further discussed below, Petitioner does not provide evidence or explanation
sufficient to show that it would have been obvious to add more PFO to the
droplets to break the emulsion.
Contrary to Petitioner’s argument, Example 4 of Ismagilov 091 does
not teach that PFO promotes droplet merging. PFO is not even mentioned in
the example. According to Petitioner, the examples in Ismagilov 091 were
“typically performed” using a mixture of PFD and PFO. Reh’g Req. 6.
Petitioner does not explain what would have led a POSA to conclude that
PFO promotes droplet merging, when it is used as surfactant in all or most of
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the examples, most of which do not involve droplet merging. Example 5,
for instance, illustrates splitting plugs. Ex. 1004, 65:17–57.
Ismagilov 091 illustrates the role of PFO in Example 13C, not
Example 4, which does not even mention PFO. In Example 13C, aqueous
plugs were formed in a carrier fluid flowing through a microchannel, where
the carrier fluid is a mixture of fluorinated oil and PFO. Ex. 1004,
72:37–41, 72:54–56. A microphotograph shows “water plugs attached to the
PDMS wall.” Id. at 72:48–51, Fig. 39. According to Ismagilov 091, “[t]his
attachment occurs when low concentrations of surfactant, or less-effective
surfactants are used” and “[i]n this case, [PFO] is less effective than
1H,1H,2H,2H-perfluorodecanol.” Id. at 72:51–54. The explicit discussion
of the role of PFO in Example 13C reinforces our finding that Ismagilov 091
teaches PFO for preventing droplets from sticking to the channel walls, but
does not teach or suggest that PFO promotes droplet merging.
Next, Petitioner argues that “in order to perform the synthesis of
biological compounds, pharmaceuticals, or nanoparticles and the protein
crystallizations that Ismagilov teaches as uses for its system, a POSA would
know that it would be necessary (and desirable) to break the emulsion to
collect the contents of the droplets for further use.” Reh’g Req. 7 (citing
Pet. 51; Ex. 1008 ¶¶ 190, 191). That argument differs from the Petition to
the extent it relies on desirability rather than necessity. The Petition argued
that the uses disclosed in Ismagilov 091 “would require breaking the
emulsions to aggregate sufficient quantities of reaction product.” Pet. 51
(emphasis added); see Ex. 1008 ¶ 191 (same).
Regardless of whether Petitioner’s argument now that emulsion-
breaking would have been necessary and desirable differs from Petitioner’s
original argument that emulsion-breaking would have been necessary,
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Petitioner did not provide evidence or explanation sufficient to show that
emulsion-breaking would have been either necessary or desirable when
synthesizing biological compounds, pharmaceuticals, or nanoparticles, as
disclosed in Ismagilov 091. Dr. Fair’s testimony that Ismagilov 091’s uses
“would require breaking the emulsions” is conclusory and unexplained.
Ex. 1008 ¶ 191 (testifying without explanation that Ismagilov’s “uses would
require breaking the emulsions to aggregate sufficient quantities of reaction
product”). In addition, Petitioner did not cite even this conclusory testimony
in its argument that emulsion-breaking was necessary. Pet. 51. Meanwhile,
Ismagilov 091 provides numerous examples of uses of its methods and
devices, but no suggestion that emulsion-breaking would be necessary or
desirable. Accordingly, we determined that Petitioner did not “direct us to
evidence sufficient to establish that it would have been obvious to place the
droplets onto a second continuous phase carrier fluid comprising a
destabilizing surfactant to destabilize the droplets, as recited in
claims 15–17.” Dec. 63. As discussed more fully below, none of
Petitioner’s arguments for rehearing persuades us that we erred in
determining that the evidence of record failed to show a reason why a person
of ordinary skill in the art would have used PFO to break the emulsions in
Ismagilov 091.
Dr. Fair’s testimony might have been persuasive if he had provided an
example of a synthesis or reaction from Ismagilov 091 where a POSA would
have found it necessary or desirable to add PFO to demulsify the droplets
after they had been separated. For example, Ismagilov Example 12 titled
“Nanoparticle Experiments with and without Plugs” compares two methods
of forming nanoparticles, one using microfluidics and droplet formation, and
the other without microfluidics or droplets. Ex. 1004, 70:49–71:19. A
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“UV-VIS spectrum” was used to evaluate whether the nanoparticles were
monodisperse or polydisperse. Id. at 71:5–7, 71:17–19. There is no mention
of how the samples were prepared for spectroscopy or of any need for
different steps, such as demulsification, that were necessary to prepare the
microfluidics sample, as compared with the non-microfluidics sample.
The closest Dr. Fair came to providing an example to illustrate his
testimony is droplets that have been stabilized with a biocompatible
fluorosurfactant. Ex. 1008 ¶ 192 (quoting Ex. 1004, 37:23–25). But nothing
in Ismagilov 091’s discussion of biocompatible fluorosurfactants suggests
anything about emulsion-breaking or the addition of another surfactant, such
as PFO, to break the emulsion.
In our view, Petitioner’s argument about emulsion-breaking is based
on impermissible hindsight. The ’722 Patent teaches a method of sample
recovery whereby the creamed emulsion is placed onto a second continuous
phase carrier fluid containing a de-stabilizing surfactant such as PFO.
Ex. 1001, 48:6–38. Petitioner incorrectly interprets Ismagilov 091 with the
benefit of this teaching.
The Request departs even more fundamentally from the Petition’s
theory of obviousness. The Petition and the Fair Declaration were based on
the theory that it would have been obvious to add a destabilizing
surfactant—PFO—to de-emulsify droplets that have been stabilized by a
first surfactant—“[f]luorosurfactants” with “biocompatibility in blood
substitutes and other biomedical applications.” Pet. 52 (emphasis omitted;
quoting Ex. 1004, 37:23–25); Ex. 1008 ¶¶ 192, 193. According to the
Petition and the Fair Declaration, “[t]o obtain the contents of droplets made
using this preferred surfactant, [t]he POSA would look to methods of
demulsification, or breaking emulsions.” Pet. 52; Ex. 1008 ¶ 192 (emphasis
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added). “This preferred surfactant” referred to what Ismagilov describes as
“[f]luorosurfactants” with “biocompatibility in blood substitutes and other
biomedical applications,” i.e., “[f]luorosurfactants terminated with
OEG[oligoethylene glycol]-groups.” Pet. 52; Ex. 1008 ¶ 192; Ex. 1004,
37:23–25.
The Petition explained that “the Ismagilov droplets were stabilized by
the long-fluorinated-tail surfactant.” Pet. 10 (citing Ex. 1017, 222:18–223:9,
Dr. Ismagilov’s testimony from a prior litigation); see also Ex. 1008 ¶ 60
(“Dr. Ismagilov testified that the droplets disclosed by Ismagilov were stable
because of the surfactant used.”). According to the Petition and the Fair
Declaration, the cited testimony discusses the OEG-terminated surfactants
disclosed in Ismagilov 091. Pet. 10 n.1; Ex. 1008 ¶ 60 n.1 (citing Ex. 1004,
37:23–45, Fig. 24). Dr. Fair explained that “[s]table droplets will cream or
sediment without, for example, coalescing with other droplets they are close
to.” Ex. 1006 ¶ 60. Thus, the obviousness case advanced in the Petition and
the Fair Declaration was premised on the theory that “it would have been
obvious to add this surfactant,” i.e., PFO, “to stable droplets,” i.e. droplets
that had been stabilized with fluorosurfactant, “in a tube or other vessel to
de-emulsify and aggregate reaction product.” Pet. 52 (emphasis added);
Ex. 1008 ¶¶ 192, 193; Ex. 1004, 37:23–25.
Petitioner’s Request abandons the theory of obviousness advanced in
the Petition and the Fair Declaration, making no mention of droplets
stabilized by a fluorosurfactant. Contrary to the arguments advanced in the
Request, Dr. Fair’s testimony does not support obviousness of adding a
destabilizing surfactant unless the droplets are stable. Ex. 1004 ¶ 193. The
only example Dr. Fair provided of stable droplets were those “made using
this preferred surfactant,” i.e., “[f]luorosurfactants” with “biocompatibility
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in blood substitutes and other biomedical applications.” Id. ¶ 193.
Dr. Fair’s testimony does not support the new arguments presented in the
Request, which rely on Example 4 of Ismagilov 091 as teaching PFO for
droplet merging. Reh’g Req. 6, 10–11. In that example, the droplets were
not stabilized by a fluorosurfactant.
For all of these reasons, Petitioner’s attempt to re-argue its case for
unpatentability of claims 15–17 is not persuasive.
D. The Panel Did Not Misapprehend or Overlook The Teachings of
Ismagilov 091
Petitioner argues that we misread Ismagilov 091 when finding that it
“teaches perfluorooctanol as a surfactant to stabilize droplets in channels,
not to destabilize or merge droplets.” Reh’g Req. 8; Dec. 63 (citing
Ex. 1004, 21:7–35). After considering Petitioner’s rehearing arguments, we
are not persuaded that we misapprehended or overlooked the teachings of
Ismagilov 091. Our finding is fully supported by the passage from
Ismagilov 091 quoted in the Final Decision. Dec. 63. There, we stated:
Ismagilov 091 teaches that “the plugs remain stable and do not
leave behind any residue as they are transported through the
channels” when “the surface tension at a plug fluid/channel wall
interface . . . is set higher than the surface tension at a plug
fluid/carrier-fluid interface . . . with a surfactant such as 10%
1H,1H,2H,2H-perfluorooctanol.”
Id. (quoting Ex. 1004, 21:11–22).
For the first time in the Request, Petitioner attempts to distinguish two
types of droplet stability: (1) stability against sticking to the channel walls
and (2) stability against coalescence or merger. Reh’g Req. 9–10. The
Petition drew no such distinction. Even if Petitioner is correct that the term
“destabilizing” in claims 16 and 17 refers to surfactants that promote droplet
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Patent 9,896,722 B2
17
coalescence (id.), that does not show error in our finding about
Ismagilov 091, which teaches PFO to stabilize droplets in channels and does
not teach PFO to destabilize or merge droplets.
The Request repeats the unsupported assertion from the Petition that
Ismagilov 091 discloses PFO “for droplet merging.” Reh’g Req. 10; Pet. 52
(Ex. 1004, 21:16–29, 61:19–21). Neither the Petition nor the Request points
to sufficient support for that assertion. The Request relies on Example 4 of
Ismagilov 091, which was neither cited nor discussed in the Petition. Reh’g
Req. 10–11. For the reasons discussed above, even if it is assumed that
Example 4 uses the same carrier fluid/surfactant mixture as disclosed in
Example 1, there is no suggestion in Ismagilov 091 that the surfactant (PFO)
plays any role in promoting the merging of droplets.
Petitioner does not show that the Final Decision misapprehended or
overlooked any teaching in Ismagilov 091 about the use of PFO for
destabilizing or merging droplets.
E. The Panel Did Not Misapprehend or Overlook Petitioner’s Arguments
or Evidence Relating to a Second Continuous Phase Carrier Fluid
Petitioner asserts that the Final Decision overlooked Petitioner’s
discussion of Patent Owner’s claim construction and Petitioner’s argument
that “a POSA would know that it would be necessary and desirable to break
the Ismagilov droplet emulsion to collect the contents of the droplets for
further use after performing Ismagilov’s synthesis or crystallization
reactions” and “the addition of a destabilizing surfactant such as PFO was a
routine, known way to do that.” Reh’g Req. 15 (citing Pet. 11–13, 18–19,
51–53; Ex. 1008 ¶¶ 62, 78, 79, 190–193). We did not overlook these
arguments. They are addressed by our finding that “[e]ven if destabilizing
surfactants were known in the art, Petitioner does not direct us to evidence
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18
sufficient to establish that it would have been obvious to place the droplets
onto a second continuous phase carrier fluid comprising a destabilizing
surfactant to destabilize the droplets, as recited in claims 15–17.” Dec. 63.
Although our finding does not expressly refer to the construction for
“continuous phase carrier fluid” relied upon by Petitioner (Pet. 19), that
construction does not change the fact that Petitioner did not direct us to
evidence sufficient to support its argument that Ismagilov 091’s disclosed
reactions “would require breaking emulsions to aggregate sufficient
quantities of reaction product.” Pet. 51. As discussed above, Petitioner did
not provide evidence or explanation sufficient to show that emulsion-
breaking would be necessary or even desirable when synthesizing biological
compounds, pharmaceuticals, or nanoparticles, as disclosed in
Ismagilov 091.
F. Petitioner Does Not Show Good Cause For Admitting New Evidence
Petitioner filed Exhibits 1088 and 1089 with its Request. These
exhibits were not of record at the time the Final Decision was entered.
Petitioner argues that good cause exists for admitting Exhibits 1088 and
1089 because it “was never given an opportunity to respond to the FWD’s
novel, erroneous theory that PFO is a stabilizing surfactant.” Reh’g Req. 15.
We disagree.
Petitioner had the burden of proving that the challenged claims are
unpatentable. There is no requirement for the Board to provide notice to
Petitioner and an opportunity to fill gaps in its case before issuing a final
decision that Petitioner did not meet its burden of proof. Allowing Petitioner
to submit new evidence under the circumstances presented here would be
inconsistent with the standard applicable to a request for rehearing, which
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Patent 9,896,722 B2
19
requires Petitioner to show that the Board overlooked or misapprehended
Petitioner’s arguments or evidence. 37 C.F.R. § 42.71(d) (2020).
Moreover, our finding that Ismagilov 091 teaches PFO as a surfactant
to stabilize droplets in channels (Ex. 1004, 21:7–35) is neither novel nor
erroneous. The finding is based on a portion of Ismagilov 091 relied upon in
the Petition, including for claims 15–17. Pet. 52 (citing Ex. 1004, 21:16–29
to show unpatentability of claims 15–17); see also Pet. 14 (summarizing
Ismagilov 091 and citing Ex. 1004, 21:7–35); Pet. 29–30 (quoting
Ismagilov 091’s disclosure that “the plugs remain stable and do not leave
behind any residue as they are transported through the channels,” citing
Ex. 1004, 21:7–35). Furthermore, Ismagilov 091’s teaching that PFO
surfactant stabilizes droplets in channels by reducing the surface tension at
the droplet/carrier fluid interface, as compared with the surface tension at the
droplet/channel wall interface (Ex. 1004, 21:7–35) is consistent with and
bolstered by Viovy’s teaching that adding PFO surfactant is one way to make
interfacial tension between the droplet and the microchannel wall larger than
the interfacial tension between the droplet and the surrounding fluid. Ex. 1059,
11:23–12:6.
Thus, Petitioner has not established good cause for admitting Exhibits
1088 and 1089. Consequently, although we do not exercise our authority
under 37 C.F.R. § 42.7(a) to expunge Exhibits 1088 and 1089, we do not
admit them. See Huawei Device Co. v. Optis Cellular Tech., LLC, IPR2018-
00816, Paper 19 at 3‒4 (PTAB Jan. 8, 2019) (precedential) (expunging
exhibits filed with a request for rehearing when the petitioner failed to
establish good cause for admitting the exhibits); see also Consolidated Trial
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20
Practice Guide 90 (Nov. 2019)8 (“Absent a showing of ‘good cause’ prior to
filing the request for rehearing or in the request for rehearing itself, new
evidence will not be admitted.”).
Even if we were to consider Exhibits 1088 and 1089, they do not
change our views. Exhibit 1088 is an excerpt from an expert rebuttal report
of Dr. Bruce Gale served by Patent Owner in an unrelated district court
litigation, and Exhibit 1089 is an excerpt from Dr. Gale’s deposition
testimony. Petitioner directs us to Dr. Gale’s opinion that Ismagilov 091
teaches that droplets merge when they contact each other. Reh’g
Req. 12–13 (citing Ex. 1088 ¶¶ 68, 70 (citing Ismagilov 091 [Ex. 1004],
9:5–7, 28:4–6, 28:67–29:1 and Ex. 1089, 91:11–16). None of the cited
evidence mentions PFO or any role it plays in promoting droplet merging.
Moreover, Dr. Gale opines that Ismagilov 091 does not disclose “pooling
droplets at all” (Ex. 1088 ¶ 63) and “does not provide any description of any
well or reservoir in which plugs are pooled so that they contact each other
without fusing” (id. ¶ 69), a position directly at odds with our findings about
Ismagilov 091 and Petitioner’s and Dr. Fair’s positions in this proceeding.
Dec. 27–28; Pet. 35–37; Ex. 1008 ¶¶ 127–129 (asserting that Ismagilov 091
discloses collection wells or reservoirs from which droplets can be collected
by micropipette).
Petitioner also directs us to Dr. Gale’s testimony that PFO “can be
used . . . in a variety of ways” and that using it as a destabilizing surfactant
to promote droplet merging “has been done before.” Req. Reh’g 13 (quoting
Ex. 1089, 126:16–23). Dr. Gale’s testimony does not provide persuasive
support for Petitioner’s argument because it fails to identify when PFO had

8 Available at https://www.uspto.gov/TrialPracticeGuideConsolidated.
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21
been used as a destabilizing surfactant to promote droplet merging, and it
fails to support Petitioner’s position that Ismagilov 091 discloses PFO for
droplet merging.
IV. CONCLUSION
We deny Petitioner’s Request for Rehearing because we determine
that Petitioner has not met its burden to show that, in the Final Decision, we
misapprehended or overlooked any matter.
V. ORDER
For the foregoing reasons, it is hereby:
ORDERED that Petitioner’s request for rehearing is denied; and
FURTHER ORDERED that Exhibits 1088 and 1089 are not admitted.
Trials@uspto.gov Paper 41
571-272-7822 Entered: July 28, 2021

UNITED STATES PATENT AND TRADEMARK OFFICE

BEFORE THE PATENT TRIAL AND APPEAL BOARD

10X GENOMICS, INC.,
Petitioner,
v.
BIO-RAD LABORATORIES, INC.,
Patent Owner.

IPR2020-00088
Patent 9,896,722 B2

Before CHRISTOPHER M. KAISER, KIMBERLY MCGRAW, and
ELIZABETH M. ROESEL, Administrative Patent Judges.
MCGRAW, Administrative Patent Judge, concurring.

I join the majority’s decision denying Petitioner’s Request for
Rehearing.
I write separately to highlight that the panel need not determine
whether the evidence of record establishes that perfluorooctanol (“PFO”), or
other fluorinated surfactants, can be used as a destabilizing agent to merge
droplets in order to deny Petitioner’s Request for Rehearing of our
determination that Petitioner did not show by a preponderance the evidence
that claims 15–17 are unpatentable over US 7,129,091 B2 (Ex. 1004,
“Ismagilov 091” or “Ismagilov”) and US Pub. No. 2002/0058332 A1
(Ex. 1006).
IPR2020-00088
Patent 9,896,722 B2
2
Petitioner’s arguments to show the unpatentability of independent
claim 14––e.g., that fluorosurfactants of Ismagilov 091 are used to stabilize
droplets so that the droplets will not merge together but rather, will separate
from the immiscible fluid based on density when in a separation chamber––
are inconsistent with Petitioner’s arguments to show the unpatentability of
dependent claims 15 through 17––e.g., that a fluorosurfactant disclosed in
Ismagilov 091 (i.e., PFO) is used to destabilize aqueous droplets so that the
droplets will merge together.
For example, the Petition asserts that “the Ismagilov droplets were
stabilized by the long-fluorinated-tail surfactant” and that the Ismagilov
emulsions “would pool stably and would float.” Pet. 10 (citing Ex. 1017,
222:18–223:9); see also Pet. 45–46 (asserting that Ismagilov discloses
separating droplets from immiscible fluid in a separation chamber as
required by claim 14 because “providing droplets of different density from
the immiscible fluid into an output well or reservoir and allowing those
droplets to float or sink relative to the oil” discloses the separating step); see
also Pet. 14 (stating that the plugs in Ismagilov 091 “are droplets that are
surrounded by an immiscible fluid” and “Ismagilov testifying regarding
creating stable ‘droplets’”).
In contrast, Petitioner argues with respect to claims 15–17 that a
person skilled in art would know that “PFO [a fluorosurfactant disclosed in
Ismagilov 091], could be used for droplet merging. Pet. 52 (citing Ex. 1004,
21:16–29, 48:25–28, 61:19–21). In its Request for Rehearing, Petitioner
asserts that each of the 17 examples disclosed in Ismagilov 091 use a 10:1
mixture of the fluorinated oil perfluordecaline to PFO. See Req. Reh’g 10
(citing Ex. 1004, 61:19–21; Pet. 52; Ex. 1008 ¶ 192). Petitioner further
asserts that Example 4 of Ismagilov describes experiments where plugs were
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Patent 9,896,722 B2
3
merged (coalesced) using that 10:1 mixture of perfluorodecaline and PFO.
Id. at 11 (citing Ex. 1004, 64:8–67, Figs. 33b–33c). Petitioner asserts that
these and other teachings of Ismagilov 091, together with other identified
disclosures “confirm that a POSA [person of ordinary skill in the art] was
familiar with PFO’s use as a destabilizing surfactant that can be added to the
continuous phase to promote merger/coalescence of droplets to destabilize
droplet emulsions.” Id. at 11 (citing, inter alia, Pet. 11–13, 51–53; Ex. 1008
¶ 62, 190–193).
Thus, Petitioner’s argument that the fluorosurfactants used in
Ismagilov (i.e., PFO) are used to stabilize droplets, made to support its
unpatentability argument of claim 14, is inconsistent with Petitioner’s
argument that a POSA would have known to add PFO to destabilize
Imsagilov’s stable droplets, made to support its unpatentability argument of
claims 15–17. Stated another way, Petitioner is arguing that fluorinated
surfactants, such as PFO, are used to create highly stable droplets in an
immiscible fluid of fluorinated oil that will not coalesce in the separation
chamber, while also arguing that the addition of PFO to stable droplets in an
immiscible fluid of fluorinated oil will destabilize the droplets. These
inconsistencies are not explained. As such, regardless of whether Ismagilov
discloses or suggests, or a person skilled in the art would have understood,
that PFO could be used to destabilize droplets, Petitioner has not sufficiently
explained its inconsistent positions that a PFO can also be used to stabilize
droplets.
Given these inconsistent arguments regarding independent claim 14
and its dependent claims 15–17, Petitioner’s arguments fail to show that the
panel’s decision that Petitioner has not shown by a preponderance of the
evidence that claims 15–17 are unpatentable should be modified.
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Patent 9,896,722 B2
4
For PETITIONER:

Samantha A. Jameson
Matthew D. Powers
Azra Hadzimehmedovic
Robert L. Gerrity
Gina Cremona
TENSEGRITY LAW GROUP LLP
samantha.jameson@tensegritylawgroup.com
matthew.powers@tensegritylawgroup.com
azra@tensegritylawgroup.com
robert.gerrity@tensegritylawgroup.com
gina.cremona@tensegritylawgroup.com

For PATENT OWNER:

David Bilsker
Kevin Johnson
Anne Toker
QUINN EMANUEL URQUHART & SULLIVAN, LLP
davidbilsker@quinnemanuel.com
kevinjohnson@quinnemanuel.com
annetoker@quinnemanuel.com