Ex Parte Lizano-González et al

Patent Trial and Appeal Board

Apr 13, 2016

12613087 (P.T.A.B. Apr. 13, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
12/613,087 11105/2009 Sergio Agustin Lizana-Gonzalez
20306 7590 04/13/2016
MCDONNELL BOEHNEN HULBERT & BERGHOFF LLP
300 S. WACKER DRIVE
32NDFLOOR
CHICAGO, IL 60606
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
ATTORNEY DOCKET NO. CONFIRMATION NO.
09-056 5664
EXAMINER
HORNING, MICHELLE S
ART UNIT PAPER NUMBER
1648
MAILDATE DELIVERY MODE
04/13/2016 PAPER
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.
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte SERGIO AGUSTIN LIZANO-GONZALEZ
and LISA ANN ESTEY
Appeal2014-000696
Application 12/613,087 1
Technology Center 1600
Before LORA M. GREEN, JEFFREY N. FREDMAN, and
RYAN H. FLAX, Administrative Patent Judges.
FLAX, Administrative Patent Judge.
DECISION ON APPEAL
This is a decision on appeal under 35 U.S.C. § 134(a) involving
claims directed to methods of preparing a biological sample comprising
leukocytes for detection of analytes associated with exosomes by treatment
of a sample comprising leukocytes with an inhibitor ofN-SMase. The
Examiner rejects claims 1-15 under 35 U.S.C. § 103(a). We have
jurisdiction under 35 U.S.C. § 6(b).
We reverse.
1 The real party in interest is IDEXX Laboratories, Inc. App. Br. at 1.
Appeal2014-000696
Application 12/613,087
STATEMENT OF THE CASE
Claims 1-15 are on appeal and can be found in the Claims Appendix
of the Appeal Brief. 2 Claims 1 and 9 are the independent claims; claim 1 is
representative and reads as follows:
1. A method for preparing a biological sample compnsmg
leukocytes for detection of analytes associated with exosomes
compnsmg:
a. collecting a biological sample comprising leukocytes from a
subject;
b. adding an inhibitor ofN-SMase to the sample.
App. Br. at 13, Claims Appendix.
The Specification describes analyte detection directed to identifying
PrPsc in biological samples. Spec. 2, 11. 21-26. The Specification explains
that PrPsc is an infectious prion that can cause transmissible spongiform
encephalopathies (TS Es), such as the disease scrapie in sheep and goats,
bovine spongiform encephalopathy in cattle, mink encephalopathy, feline
spongiform encephalopathy, chronic wasting disease in deer and elk, and in
humans can cause kuru, Creutzfeldt-Jakob disease, Gerstmann-Straussler-
Scheinker Syndrome, fatal insomnia, and variant Creutzfeldt-Jacob disease.
Spec. 4, 11. 13-21.
The Specification describes that an embodiment of the invention
provides improved methods of detecting such analytes found associated with
exosomes or leukocytes by obtaining a biological sample comprising
leukocytes and adding an inhibitor ofN-SMase to the sample. Spec. 4, 11.
2 All references herein to the "Specification" or "Spec." are to the appealed
application as filed.
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22-24. The advantage of this method, so explains the Specification, is that
PrPsc can be associated with exosomes (cellular membrane-bounded
subcellular compartments found in neurons and cells of the immune system),
but that signal loss for PrPsc as an analyte occurs in the time interval
between biological sample collection and signal detection, so, by inhibiting
exosome release via an N-SMase inhibitor, one may preserve the detection
signal for a longer time. Spec. 2, 1. 28-3, 1. 6.
The following ground of rejection is on appeal:
Claims 1-15 under 35 U.S.C. § 103(a) as being unpatentable over
Prusiner,3 Fevrier,4 Zha,5 and Trajkovic.6 Final Action 2.
FINDINGS OF FACT
FF 1. PrPsc is formed from normal, cellular PrP isoform (Pr Pc)
and prion diseases result from conversion of Pr Pc into PrPsc, which is
necessary for the transmission and pathogenesis of the transmissible
neurodegenerative diseases of animals and humans, such as spongiform
encephalopathies. Prusiner col. 1, 11. 26-49.
FF2. Detecting prions and PrPsc is important to the study of
prion diseases, such as scrapie of sheep and goats, chronic wasting disease
3 U.S. Patent 6,620,629 to Prusiner et al. (issued Sept. 16, 2003; hereinafter
"Prus in er").
4 Fevrier et al., Cells Release Prions in Association with Exosomes, 101
PNAS 9683-9688 (June 29, 2004) (hereinafter "Fevrier").
5 Zha et al., Sphingomyelinase Treatment Induces ATP-independent
Endocytosis, 140 J. CELL BIO. 39--47 (Jan. 12, 1988) (hereinafter "Zha").
6 Trajkovic et al., Ceramide Triggers Budding of Exosome Vesicles into
Multivesicular Endosomes, 319 SCIENCE 1244--247 (Feb. 29, 2008)
(hereinafter "Trajkovic").
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Application 12/613,087
of deer and elk, bovine spongiform encephalopathy of cattle, kuru in
humans, Creutzfeldt-Jakob Disease in humans, Gerstmann-Straussler-
Scheinker Disease in humans, and fatal familial insomnia in humans.
Prusiner col. 1, 1. 50-col. 3, 1. 11; see also Spec. i-fi-f l, 10 (discussing
detecting PrPsc in buffy coat fractions of blood and from antemortem
transmissible spongiform encephalopathies samples).
FF3. The Specification indicates it was known that "PrPsc can
be detected in buffy coat fractions of blood" and that "[d]etection of PrPsc
from buffy coat fractions provides a way to concentrate the sample and to
remove interfering substances in plasma." Spec. i-f l (Background of the
Invention).
FF4. The Specification indicates it was known that "the
magnitude of detection [of PrPsc in buffy coat fractions of blood] is
inversely related to the age of the blood sample at the time of processing"
because "'aged' buffy coat samples retain less signal than matched buffy
coat samples that are processed immediately [upon obtaining the samples]."
Spec. i-f l (Background of the Invention).
FF5. Prusiner disclosed an "assay [for] determining levels of
total PrP8c in a sample" and that "[t]o avoid progression and/or possible
transmission of disease, it is important to identify [the presence of] PrP8c in
biological fluids." Prusiner Abstract; col. 9, 11. 51-53; see also Final Action
3 and Ans. 5---6 (discussing Prus in er' s disclosure).
FF6. Prusiner disclosed a diagnostic assay for prion infection
in samples such as "white blood cells (WBC) isolated from prion-infected
whole blood" and "used to show that the PrP8c [is] present in prion infected
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white blood cells (WBC)." Prusiner col. 4, 11. 1---6; col. 20, 11. 19-56; see
also Final Action 3 and Ans. 5---6 (discussing Prusiner's disclosure).
FF7. Prusiner did not disclose that prions are an analyte
associated with exosomes and did not disclose the use of an N-SMase
inhibitor. See Final Action 3; Ans. 6.
FF8. Fevrier disclosed that PrPsc is associated with exosomes.
Fevrier 9683, 9688; see also Final Action 3 and Ans. 6 (discussing Fevrier
disclosure).
FF9. Fevrier disclosed that exosomes bearing PrPsc are
infectious. Fevrier 9683.
FFlO. Fevrier disclosed:
There is increasing evidence that monocytes and bone marrow-
derived and follicular dendritic cells accumulate infectious
prions and play a key role in the onset of disease (4). Most of
these cells actively secrete exosomes ( 17, 18), and Pr Pc is present
in exosomes secreted by bone marro\'l/=derived dendritic cells
(our unpublished observations). Future studies are needed to
determine whether exosomes secreted by these cells participate
in the propagation of this infectious agent in vivo.
Fevrier 9688.
FFl 1. Zha disclosed that treating mammalian cells with SMase
(exogenous sphingomyelinase) "rapidly induces formation of numerous
vesicles that pinch off from the plasma membrane; the process is complete
within 10 min after adding SMase." Zha Abstract; see also Final Action 3
and Ans. 6 (discussing Zha disclosure).
FF12. Trajkovic disclosed "[ e ]xogenous SMase treatment ...
can induce the formation of vesicles" and that upon treating "Oli-neu [mouse
oligodendroglial] cells with the neutral sphingomyelinase (nSMase)
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inhibitor, GW4869[] [e]xosome release was markedly reduced" and "[t]he
effect was also observed after treatment with the two structurally unrelated
nSMase inhibitors, spiroexpoxide and glutathione." Trajkovic 1246; see
also Final Action 3--4 and Ans. 6 (discussing Trajkovic disclosure).
FF13. None of Prusiner, Fevrier, Zha, and Trajkovic disclosed
or suggested that inhibiting exosome release can enhance detection of or
prolong the detection period for an analyte associated with exosomes.
FF14. None of Prusiner, Fevrier, Zha, and Trajkovic disclosed
or suggested using an inhibitor of exosomal vesicular budding to optimize
detection of PrPsc by co-localizing and amplifying the signal of PrPsc.
FF15. None of Prusiner, Fevrier, Zha, and Trajkovic disclosed
or suggested inhibiting exosomal vesicular budding to identify which cell
type harbored the PrPsc before cellular release of PrPsc.
DISCUSSION
Appellants assert that the Examiner has not established a prima facie
case for obviousness because, in part, there has not been a sufficient
showing that there would have been motivation to combine the cited prior
art. We agree.
While the various recited elements of the claimed invention may be
identifiable in the cited prior art, an invention
composed of several elements is not proved obvious merely by
demonstrating that each of its elements was, independently,
known in the prior art. Although common sense directs one to
look with care at a patent application that claims as innovation
the combination of two known devices according to their
established functions, it can be important to identify a reason
that would have prompted a person of ordinary skill in the
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relevant field to combine the elements in the way the claimed
new invention does.
KSR Int'! Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007). Moreover,
combining references can be based on common sense as long as the
reasoning is explained sufficiently. See Perfect Web Techs., Inc. v. InfoUSA,
Inc., 587 F.3d 1324, 1328-29 (Fed. Cir. 2009) (emphasis added).
Here, the Examiner's rationale for combining the cited references
lacks sufficient explanation. The Examiner acquiesces to Appellants'
argument that the references themselves do not identify the specific problem
addressed by the invention as disclosed in the Specification, which is
improving/prolonging detection of PrPsc associated with exosomes and
leukocytes. App. Br. 5; Ans. 8-9 (acknowledging this shortcoming of the
applied references). Instead, the Examiner determined that there were two
other, alternative reasons for making the prior art combination:
(1) inhibiting exosomal vesicular budding to optimize detection of PrPsc by
co-localizing and thereby amplifying the signal of PrPsc; and/or
(2) inhibiting exosomal vesicular budding to identify which cell type harbors
the PrPsc before cellular release of PrPsc. Ans. 8-9. The Examiner,
however, does not rely on or identify any evidentiary support for these
reasons. Final Action 5; Advisory Action 2 (dated Sept. 6, 2012); Ans. 8-
10. Stated differently, the Examiner has not presented evidence showing
that inhibiting exosomal vesicular budding would optimize PrPsc detection
by co-localization/amplification or assist in identifying cell types, or that
these were established, motivating results. See In re Zurko, 258 F.3d 1379,
1386 (Fed. Cir. 2001) ("[T]he Board [or examiner] must point to some
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concrete evidence in the record in support of these findings" to satisfy the
substantial evidence test). Thus, the Examiner has failed to demonstrate by
a preponderance of the evidence that claims on appeal are rendered obvious
by the combination of Prusiner, Fevrier, Zha, and Trajkovic.
For these reasons, the rejection of claims 1-15 under 35 U.S.C.
§ 103(a) is reversed.
SUMMARY
The rejection of claims 1-15 under 35 U.S.C. § 103(a) is reversed.
REVERSED
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