University of Utah Research Foundation

Patent Trials and Appeals Board

Nov 29, 2021

2021001649 (P.T.A.B. Nov. 29, 2021)

UNITED STATES PATENT AND TRADEMARK OFFICE
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O. Box 1450
Alexandria, Virginia 22313-1450
www.uspto.gov
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
15/520,795 04/20/2017 Bruce K. Gale 00846-U5742.PCT.US 4777
20551 7590 11/29/2021
THORPE NORTH & WESTERN, LLP.
P.O. Box 1219
SANDY, UT 84091-1219
EXAMINER
BERKE-SCHLESSEL, DAVID W
ART UNIT PAPER NUMBER
1651
NOTIFICATION DATE DELIVERY MODE
11/29/2021 ELECTRONIC
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
following e-mail address(es):
patentdocket@tnw.com
warren.archibald@tnw.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte BRUCE K. GALE, DOUGLAS T. CARRELL,
KRISTIN MURPHY, JIM HOTALING, and JIYOUNG SON1

Appeal 2021-001649
Application 15/520,795
Technology Center 1600

Before ERIC B. GRIMES, TINA E. HULSE, and JOHN E. SCHNEIDER,
Administrative Patent Judges.

GRIMES, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims to a
method of separating sperm cells, which have been rejected as obvious. We
have jurisdiction under 35 U.S.C. § 6(b).
We REVERSE.
STATEMENT OF THE CASE
“Non-obstructive azoospermia (NOA) [is] the most severe form of
male factor infertility. . . . Conception for NOA patients is dependent on a
surgical procedure to extract sperm directly from the testis, called

1 Appellant identifies the real parties in interest as the University of Utah and
University of Utah Research Foundation. Appeal Br. 3. “Appellant” refers to
“applicant” as defined in 37 C.F.R. § 1.42.
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Application 15/520,795

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microsurgical testicular sperm extraction (mTESE),” which is “often
unsuccessful due to major limitations with current techniques.” Spec. 1:9–
20. “[M]icrofluidic devices that have been developed for sperm isolation
utilize the property of sperm motility. . . . However, because testicular sperm
are not motile, existing technologies are not suitable for isolating sperm
from NOA testicular tissue specimens.” Id. at 2:10–13.
The Specification states that a microfluidic separating system having a
fluid channel with a spiral configuration “takes advantage of the inertial lift
and viscous drag forces acting on particles of various sizes to achieve
differential migration, and hence separation, of microparticles, such as
sperm.” Id. at 12:16–19. More specifically, the forces within “the spiral
microchannel geometry cause the larger particles to occupy a single
equilibrium position near the inner microchannel wall. The smaller particles
migrate to the outer half of the microchannel,” forming “two distinct particle
streams which may be collected in two separate outlets.” Id. at 12:20–24.
The Specification states that “[s]perm may exhibit unique behavior
when compared to cells of a similar size using inertial microfluidic channels
because of their long tails, which should aid in their rapid purification and
collection. Thus, spiral channels can be used to separate immotile sperm
from red blood cells and other contaminating cells.” Id. at 18:22–25.
Claims 1–6, 33, 34, and 36–43 are on appeal.2 Claim 1, the only
independent claim, is illustrative and is reproduced below:

2 Claim 35 is also pending. The Examiner withdrew the rejection of claim 35
under 35 U.S.C. § 112(b). Ans. 8. Thus, claim 35 is not subject to any
outstanding rejection.
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Application 15/520,795

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1. A method of separating sperm cells, comprising:
obtaining a microfluidic separating system having a fluid
channel and a plurality of outlets;
and
disposing a sperm sample in the fluid channel,
wherein flow of the sperm sample in the fluid channel
facilitates segregation of materials in the sperm sample
based on size and shape into a plurality of size and shape
fractions, such that each one of the plurality of outlets
receives a different size and shape fraction of the
materials in the sperm sample.
Appeal Br. 24 (Claims Appendix).
OPINION
Claims 1–6, 33, 34, and 36–43 stand rejected under 35 U.S.C. § 103
based on Papautsky3 and Takayama.4 Final Action5 7. The Examiner finds
that “Papautsky teaches a method of separating particles, including viable
cells, . . . wherein the system separates the cells based upon size.” Id. The
Examiner also finds that “Papautsky does not explicitly state sperm cells as
being the target cell population for the utilization of the method. Papautsky
broadly describes any cell. See paragraph [0004].” Id. at 7–8.
The Examiner finds that “Takayama provides a method of separating
motile sperm cells from non-motile sperm cells, by subjecting the cells to a
microfluidic device.” Id. at 8. “Takayama notes that the method could be
used for improving sperm samples for in vitro fertilization.” Id.

3 2011/0096327 A1, published Apr. 28, 2011.
4 2008/0187991 A1, published Aug. 7, 2008.
5 Office Action mailed Nov. 26, 2019.
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The Examiner concludes that “Papautsky notes that the cell separation
techniques used by Takayama, and others, could damage the cells; as such,
the ordinary artisan would be motivated to utilize Pappautsky’s [sic] method
to separate sperm cells, because it would not provide the same cellular
damage that would be expected by other techniques.” Id. at 8–9.
Appellant argues, among other things, that “Takayama intentionally
targets motile sperm cells and considers non-motile sperm undesirable.”
Appeal Br. 21. Appellant also argues that “Takayama’s method of separation
relies on the activity of motile sperm cells to swim their way into a different
laminar flow location.” Id. at 22. Thus, Appellant argues,
Takayama fails to provide any rationale, motivation, or reason
to expect the system of Papautsky to be effective at separating
materials of similar or the same size since the separation
dynamics involved in Papautsky . . . are not based on motility.
Rather, since motile sperm and non-motile sperm have common
particle-diameters, under the core assumptions of Papautsky
one would expect no separation due to the Dean’s or other
forces active in that reference.
Id.
We agree with Appellant that the Examiner has not persuasively
shown that the method of claim 1 would have been obvious to a person of
ordinary skill in the art based on Papautsky and Takayama. Papautsky
discloses “a spiral microchannel particle separator for separating particles
from a particle-laden solution.” Papautsky ¶ 52. Papautsky states that “[t]he
dominant inertial forces and the Dean rotation force due to the spiral
microchannel geometry cause the larger particles to occupy a single
equilibrium position near the inner microchannel wall. The smaller particles
migrate to the outer half of the microchannel.” Id. “The combined effect of
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these forces results in the formation of distinct particle streams based on
particle size.” Id. ¶ 57.
Papautsky states that “separation of cells was also achieved.” Id. ¶ 99.
“Based on the size of the[] cells, the mixture was passed through a . . .
[microchannel] to collect the bigger ~15 μm diameter cells from outlet 206a
and the smaller ~8 μm diameter cells from outlet 206b.” Id. Papautsky also
states that “particles with a size difference of as little as 2 μm may be
separated. . . . When the channel dimensions are scaled up, larger particles
having small size difference can also be separated. For instance, white blood
cells (10–20 μm) can be separated from red blood cells (8 μm).” Id. ¶ 138.
Thus, Papautsky teaches separating particles, including cells, of
different sizes in a mixed solution based on the migration of different-sized
particles to different areas in a microchannel under the influence of inertial
lift and Dean drag forces. Papautsky discloses separating cells of different
sizes using its method, but does not mention separating sperm cells from
other components of a sample, as recited in claim 1.
Takayama states that “[t]he separation, or ‘sorting’ of motile from
lesser-motile and/or non-motile particles has numerous applications. . . . An
especially significant application is the sorting of sperm cells.” Takayama
¶¶ 5–6. Takayama states that, for in vitro fertilization, “if the donor’s sperm
count is low, and especially if contaminated with non-motile sperm, . . . and
other cells and seminal debris, the success rate is raised considerably when
the motile sperm are used.” Id. ¶ 6.
Takayama discloses a method of sorting motile and non-motile
particles “by establishing a non-turbulent and preferably laminar flow stream
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. . . containing motile and non-motile or lesser-motile particles to be sorted,
and contacting this sort stream with a second non-turbulent and preferably
co-laminar media flow stream.” Id. ¶ 10. “The mobility of the motile
particles allow them to enter the media stream along the interface between
the media and sort streams, while non-motile or lesser-motile particles
remain substantially within the sort stream.” Id.
With reference to its Figures 2a–2c, Takayama states that “[t]he sort
stream 11 contains motile 13 and non-motile sperm 14 as well as other non-
motile particles.” Id. ¶ 23. Takayama notes that “the size of the media stream
. . . is considerably greater than the sort stream” because, “[s]ince sperm . . .
assume an essentially random distribution in the total liquid within a short
period, a larger media stream volume will necessarily contain a larger
fraction of total motile sperm 13.” Id.
Takayama’s system thus achieves separation of motile sperm cells
from non-motile sperm cells based on the ability of the motile cells to move
from the input sort stream into the adjacent media stream, while the non-
motile cells remain in the sort stream. The two streams are then directed to
different outlets. Id. ¶ 10.
By contrast, Papautsky’s system is based on inertial lift and Dean drag
forces acting on particles that are passively flowing in a fluid carrier, causing
particles of different sizes to find different equilibrium positions in the
microchannel. Papautsky’s method thus depends on the particles being
incapable of moving independently of the lift and drag forces.
Because Takayama’s system is intended to separate motile sperm
from non-motile particles, based on the motility of the desired cells, while
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Papautsky’s system is intended to separate particles (including cells) on the
basis of size without accounting for motility of the desired particles, we
agree with Appellant (Appeal Br. 22) that the Examiner has not shown that
Takayama would have led a skilled artisan to use Papautsky’s method and
system to separate sperm cells.
The Examiner notes that “Appellant states ‘motile and non-motile
sperm cells have basically the same particle size.’” Ans. 13. The Examiner
states, however, that “Appellant has provided no evidence for this assertion,
since a non-motile sperm cell can include sperm cells that lack a flagellum,
possess excess flagella, have multiple heads, etc.” id.
We do not agree with the Examiner’s apparent reasoning that a skilled
artisan would be motivated to use Papautsky’s system to separate motile and
non-motile sperm based on an expectation that they would have different
sizes. The Examiner has not pointed to evidence in the record that the size of
non-motile and motile sperm would be expected to differ to a degree that
would allow them to be separated using Papautsky’s method.
Although the Examiner faults Appellant for not citing evidence
showing that motile and non-motile sperm are similar in size, the Examiner
also cites no evidence showing that they are not. “An examiner bears the
initial burden of presenting a prima facie case of obviousness.” In re Huai-
Hung Kao, 639 F.3d 1057, 1066 (Fed. Cir. 2011). “After evidence or
argument is submitted by the applicant in response, patentability is
determined on the totality of the record, by a preponderance of evidence
with due consideration to persuasiveness of argument.” In re Oetiker, 977
F.2d 1443, 1445 (Fed. Cir. 1992).
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We conclude that the rejection on appeal is not supported by a
preponderance of the evidence of record. We therefore reverse the rejection
of claims 1–6, 33, 34, and 36–43 under 35 U.S.C. § 103 based on Papautsky
and Takayama.
DECISION SUMMARY
In summary:
Claims
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
1–6, 33, 34,
36–43
103 Papautsky, Takayama 1–6, 33,
34, 36–43

REVERSED