Kenneth M. Evans et al.

Patent Trials and Appeals Board

Aug 12, 2019

14581536 - (D) (P.T.A.B. Aug. 12, 2019)

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.
14/581,536 12/23/2014 Kenneth M. Evans XY-7 (US-7) 1004
114661 7590 08/12/2019
XY, LLC
22575 State Highway 6 South
Navasota, TX 77868
EXAMINER
VAN BUREN, LAUREN K
ART UNIT PAPER NUMBER
1651
NOTIFICATION DATE DELIVERY MODE
08/12/2019 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):
patents@stgen.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte KENNETH M. EVANS and ERIK B. VAN MUNSTER1
__________

Appeal 2019-002784
Application 14/581,536
Technology Center 1600
__________

Before RYAN H. FLAX, RACHEL H. TOWNSEND, and
CYNTHIA M. HARDMAN, Administrative Patent Judges.

HARDMAN, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims to a
method of sorting sperm in a flow cytometer, using certain beam shaping
optics. The Examiner rejected the claims as obvious over the prior art. We
have jurisdiction under 35 U.S.C. § 6(b).
We affirm.
STATEMENT OF THE CASE
According to the Specification, “[a] significant problem with
conventional flow cytometer technologies can be the orientation of objects,
particles, or cells in the sheath fluid stream. This can be particularly
problematic when the object or cell is irregular in shape with respect to more

1 Appellants identify “XY, LLC” as the real party in interest. Br. 3.
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than one axis, such spermatozoa for example.” Spec.2 3:1–4. The
Specification states that reducing the height of the beam shape can improve
the purity of sorted populations of X- and Y- chromosome bearing bovine
sperm. Id. at 20:23–26.
Claims 14 and 17–23 are on appeal. Final Act. 5. Claim 14, the only
independent claim, reads as follows:
14. A method of sorting sperm having an associated
light emission material coupled to nuclear DNA which stains X-
chromosome bearing sperm and Y-chromosome bearing sperm
in differing amounts comprising:
a) establishing a fluid stream;
b) producing an irradiation beam directed at the fluid
stream;
c) shaping the irradiation beam into an elliptical beam
pattern having a beam height of 20 micrometers and a beam
width that provides a uniform exposure to sperm at the periphery
of the irradiation beam when the flow cytometer is operated at
event rates greater than 10,000 events per second; and
d) detecting emissions from sperm cells passing through
the beam pattern.
Br. 20 (Claims Appendix).

2 Citations to the Specification herein reference the Substitute Specification
filed Feb. 13, 2015.
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Claims 14 and 17–23 stand rejected under 35 U.S.C. § 103 as obvious
over Johnson,3 Johnson 1986,4 Unterleitner,5 Dertinger,6 and the Scientist
Article.7 Final Act. 5–6.
ANALYSIS
“[T]he examiner bears the initial burden . . . of presenting a prima
facie case of unpatentability. If that burden is met, the burden of coming
forward with evidence or argument shifts to the applicant.” In re Oetiker,
977 F.2d 1443, 1445 (Fed. Cir. 1992). We have considered those arguments
made by Appellants in the Appeal Brief; arguments not so presented in
Appellants’ brief are waived. See 37 C.F.R. § 41.37(c)(1)(iv) (2015); see
also Ex parte Borden IV, 93 USPQ2d 1473, 1474 (BPAI 2010) (informative)
(“Any bases for asserting error, whether factual or legal, that are not raised
in the principal brief are waived.”).
Appellants focus their arguments on claim 14, and do not provide any
separate arguments for the dependent claims. Accordingly, the dependent
claims stand or fall with independent claim 14. 37 C.F.R. § 41.37(c)(1)(iv).

3 Lawrence A. Johnson, Sex Preselection by Flow Cytometric Separation of
X and Y Chromosome-bearing Sperm Based on DNA Difference: a Review,
7 REPROD. FERTIL. DEV. 893–903 (1995) (“Johnson”).
4 L.A. Johnson et al., Modification of a Laser-Based Flow Cytometer for
High-Resolution DNA Analysis of Mammalian Spermatozoa, 7 CYTOMETRY
268–73 (1986) (“Johnson 1986”).
5 Fred C. Unterleitner, US 4,498,766, issued Feb. 12, 1985 (“Unterleitner”).
6 Stephen Dertinger et al., US 5,858,667, issued Jan. 12, 1999 (“Dertinger”).
7 James Kling, Flow Cytometry: It’s Not Just for Immunologists Anymore,
The Scientist, June 1997, https://www.the-scientist.com/?articles.view
/articleNo/18499/title/Flow-Cytometry-lt-s-Not-Just-For-lmmunologists-
Anymore/ (“Scientist Article”).
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The Examiner determined that the claims would have been obvious
over Johnson, Johnson 1986, Unterleitner, Dertinger, and the Scientist
Article. Final Act. 5–6. To summarize, the Examiner found that Johnson
and Johnson 1986 teach methods of using a flow cytometer to sort sperm
based on whether they carry X- or Y- chromosomes. Id. at 6–7. The
Examiner also found that Johnson 1986 teaches using a beam focused to a
16 x 200 µm ellipses, while Dertinger teaches using a beam height of 20 µm.
Id. at 7. The Examiner further found that beam height and width are result-
effective variables, as evidenced by Unterleitner. Id.
The Examiner found that the Scientist Article teaches a particular
commercially-available flow cytometer (the MoFlo by Cytomation, Inc.),
which can perform cell sorting at rates exceeding 25,000 cells per second,
and which had been used to sort chromosomes. Id. at 7–8. The Examiner
stated that “a person of ordinary skill in the art would have used routine
experimentation and optimization when adjusting the flow cytometer device
to result in the most accurate cell sorting experience permissible,” and
“[t]hus, it would have been obvious for there to have been 10,000 events per
second.” Id. at 3.
The Examiner concluded:
A person of ordinary skill in the art is going to modify the
flow cytometer device used to sort cells/chromosomes in order
to guarantee the highest sample purity and fastest speed. Johnson
provides elliptical beam dimensions of 16x200 so it is easily
conceivable that with a few optimizing adjustments on the
MoFlo device, the height could easily be adjusted to 20
micrometers and the width appropriately modified as well.
Dertinger another reference even utilizes a height of 20
micrometers when sorting cells. Unterleinter [sic] is being used
to show that parameters on the scope can be adjusted to fit the
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needs of the user. Thus, it would have made sense to have
optimized the height, the width, and the events. Unterleinter [sic]
shows that such adjustments are routinely performed and do not
rise to the level of novelty. Applicants are not claiming novel
adjustments made to the MoFlo scope or use of different/unique
lasers. Thus, it would have been expected that all consumer
available MoFlo sorting devices were capable of 10,000 events
and having uniform exposure at the periphery.
Ans. 9–10.
We adopt the Examiner’s findings of fact with respect to the scope
and content of the prior art (Final Act. 2–3, 5–8; Ans. 4–7, 8–11). We
determine that the Examiner has established a prima facie case for the
obviousness of the appealed claims. We address Appellants’ arguments
below.
Appellants argue that neither Johnson, Johnson 1986, nor the Scientist
Article disclose the claimed beam height and width parameters. Br. 11–13.
This argument is not persuasive. It is well-settled that absent unexpected
results, “[w]here the general conditions of a claim are disclosed in the prior
art, it is not inventive to discover the optimum or workable ranges by routine
experimentation,” where the optimized variable is a result-effective variable.
In re Applied Materials, Inc., 692 F.3d 1289, 1295 (Fed. Cir. 2012) (quoting
In re Aller, 220 F.2d 454, 456 (CCPA 1955)).
Here, as the Examiner pointed out (and Appellants did not dispute),
Appellants “are not claiming novel adjustments” to flow cytometry devices.
Ans. 9–10. The claimed beam height and width are selected from the range
of height and width parameters that were known in the prior art. Indeed,
Dertinger teaches using a beam height of 20 µm, demonstrating that the
claimed beam height was known in creating an elliptical beam focused at the
sample stream. Final Act. 7 (citing Dertinger 6:39–40). Further, we agree
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with the Examiner that Unterleitner teaches that beam height and width are
result-effective variables for creating an optimized energy distribution of an
elliptical focal spot thereby affecting fluorescence sensitivity. Id. (citing
Unterleitner at, e.g., 2:40–68). Specifically, Unterleitner teaches that
elongating the focal spot of the laser beam improves fluorescence sensitivity
and reduces sensitivity to particle stream flow rate (i.e., stream diameter).
Unterleitner 2:29–68. Unterleitner further teaches that this optimization
achieves “best . . . resolution of slightly differently stained subpopulations of
samples.” Id. at 2:59–65; see also id. at 2:46–49 (“As a result of the features
of the present invention optimization of measurement of almost identically
stained fluorescent particles may be made.”). Moreover, Unterleitner
suggests that such adjustments “are adaptable to” a variety of flow
cytometry devices. Id. at 2:58–68.
Appellants argue that Unterleitner does not generally teach optimizing
beam height and width, but rather teaches tilting the system’s lens to change
both beam height and width in set combinations. Br. 11–12. We are not
persuaded by this argument, because as the Examiner pointed out, “nothing
in the claim language [] actually states that parameters such as height and
w[idth] must [be] adjusted independently.” Final Act. 3. Further,
Appellants have not argued that the optimization methods taught in
Unterleitner could not have been used by one of ordinary skill in the art at
the relevant time to achieve the claimed beam height and width. We note
that we have considered the Declaration of Mike Evans Under 37 C.F.R.
§1.132, dated Jan. 5, 2018 (“Evans Decl.”), and as we discuss further below,
the declarant did not address Unterleitner.
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Appellants also argue that the sort speeds disclosed in the Scientist
Article merely “provide[] a top end, without any context with respect to the
type of cells [that] are being sorted,” and there is no reasonable expectation
of success because, e.g., the devices described in the Johnson references
“appear incapable of performing at these rates for sorting sperm.” Br. 12.
We are not persuaded by this argument. First, while the Scientist Article
does not directly link the so-called “top end” speed of the MoFlo with a
particular cell type, we do note that it, nevertheless, states that the MoFlo
has been successfully used in both cell sorting and human chromosome
sorting, i.e., sorting of particles of differing shape and DNA content.
Second, the rejection does not require that the devices described in Johnson
carry out the sort rates described for the MoFlo device. Rather, the
Examiner stated that “it would have been desirable to have utilized the
MoFlo device in place of the Epics V taught in the Johnson reference.” Ans.
11; see also Final Act. 2, 7–8. Appellants have not persuasively argued or
provided persuasive evidence that there would not have been a reasonable
expectation of success in sorting sperm at greater than 10,000 events per
second on the MoFlo device, particularly after optimizing the beam shape as
taught by Unterleitner.
Appellants additionally assert that the rejection combines features
from general embodiments with features from sperm-sorting methods, and
“does not account for the fact that sperm sorting is a unique application of
flow cytometry,” including because it “requires identifying extremely
closely related populations of cells.” Br. 13–14 (discussing 2–4% difference
between the nuclear DNA content of an X chromosome-bearing sperm and a
Y chromosome-bearing sperm). Appellants also explain that at increasing
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event rates, a wider sample stream is used, leading to increased variance in
the stain-laser interaction at the center of the laser beam versus the periphery
of the beam. Id. at 14.
We are not persuaded by Appellants’ arguments. Unterleitner teaches
that optimizing beam spot shape addresses the types of problems raised by
Appellants. Specifically, as discussed above, Unterleitner teaches that
optimizing the beam spot shape improves “resolution of slightly differently
stained subpopulations of samples.” Unterleitner 2:59–65; see also id. at
2:46–49. Unterleitner also teaches that optimizing the beam spot shape
results in improved fluorescence sensitivity and reduced sensitivity to
particle stream flow rate, i.e., stream diameter (Unterleitner 2:40–46), thus
suggesting that optimization improves uniformity of exposure as stream
width increases (e.g., due to increased event rates).
Relying on In re Stepan Co., 868 F.3d 1342 (Fed. Cir. 2017),
Appellants argue that the Examiner has failed to explain why it would have
been routine optimization to arrive at the claimed invention. Br. 14–16. We
disagree. The Examiner indicated that the goal of the routine optimization
would have been to achieve “the most accurate cell sorting experience
permissible,” and relied on portions of Unterleitner that made clear that
adjusting beam height and width improves fluorescence sensitivity and
reduces sensitivity to particle stream flow rate (i.e., stream diameter). Final
Act. 3, 7 (citing, e.g., Unterleitner 2:40–67). We find that these are credible
reasons that would have motivated a person of ordinary skill in the art to
optimize beam dimensions.
Finally, Appellants assert that their claimed invention “demonstrates
unexpectedly good results” compared to the prior art. Br. 16–17. A prima
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facie case of obviousness may be rebutted “where the results of optimizing a
variable, which was known to be result effective, are unexpectedly good.”
In re Applied Materials, Inc., 692 F.3d at 1295 (citing In re Boesch, 617
F.2d 272, 276 (CCPA 1980)). To be probative of nonobviousness,
unexpected results must be “different in kind and not merely in degree from
the results of the prior art.” Galderma Labs., L.P. v. Tolmar, Inc., 737 F.3d
731, 739 (Fed. Cir. 2013) (quoting Iron Grip Barbell Co. v. USA Sports,
Inc., 392 F.3d 1317, 1322 (Fed. Cir. 2004)).
Appellants assert that in an experiment on bovine sperm, beam
dimensions that “closely approximate” those claimed maintained Peak to
Valley Ratios (PVRs) greater than 85%, compared to about 70–75%
observed when using the beam dimensions disclosed in Johnson 1986. Br.
17 (citing Evans Decl. ¶ 23); see also Evans Decl. ¶ 16 (discussing beam
dimensions employed in the experiment). Appellants also assert that in an
experiment involving sheep sperm, beam dimensions closely approximating
those claimed maintained a PVR greater than 85%, whereas when using the
beam dimensions disclosed in Johnson 1986, PVR “fell off significantly at
an event rate[] greater than 10,000 events per second.” Id. (citing Evans
Decl. ¶ 25). Finally, Appellants assert that the Specification evinces that the
claimed optics resulted in a 2–3% improvement in the purity of sorted sperm
compared to that achieved by a prior art beam dimension (30x80 µm). Id.
(citing Evans Decl. ¶ 29).
“Results which differ by percentages are differences in degree rather
than kind, where the modification of the percentage is within the capabilities
of one skilled in the art at the time.” Galderma Labs., 737 F.3d at 739.
When differences based upon degree are asserted, the evidence must show
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that the claims and prior art “differed in such an appreciable degree that the
difference was really unexpected.” In re Merck & Co., 800 F.2d 1091, 1099
(Fed. Cir. 1986). Here, Appellants’ asserted unexpected results consist of
results which differ from the prior art by percentages—i.e., differences in
degree, rather than kind.
Even if we credit the asserted differences in PVRs and purity rates, on
this record we do not find this evidence sufficient, when considered together
with the evidence of obviousness, to establish the claims to be non-obvious.
As discussed above, Unterleitner teaches that optimizing beam shape results
in improvements in fluorescence sensitivity and reduced sensitivity to
particle stream flow rate. The Evans Declaration, however, does not address
Unterleitner’s teachings regarding optimizing elliptical beam shape to
improve fluorescent sensitivity to resolve slightly differently-stained
subpopulations of a sample. Stated differently, while the Evans Declaration
asserts that the observed differences are unexpected improvements over the
prior art beam shapes used in Johnson and reported in the Specification, it
does not address whether the differences are unexpected when considering
the improved sensitivity that results from beam optimization, as taught by
Unterleitner. Accordingly, we determine that Appellants have not presented
persuasive evidence of unexpected results.
For the reasons above, we are not persuaded that the Examiner erred
in making a prima facie case of obviousness. Nor are we persuaded that
there is evidence rebutting such a case for obviousness.
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SUMMARY
We affirm the rejection of claims 14 and 17–23 under 35 U.S.C. § 103
as obvious over Johnson, Johnson 1986, Unterleitner, Dertinger, and the
Scientist Article.
TIME PERIOD FOR RESPONSE
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(1)(iv).

AFFIRMED