Ex Parte Pacholski et al

Patent Trial and Appeal Board

Feb 7, 2017

12683895 (P.T.A.B. Feb. 7, 2017)

United States Patent and Trademark Office
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
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APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
12/683,895 01/07/2010 Claudia Pacholski 0321.72679D1 4076
24978 7590 02/09/2017
GREER, BURNS & CRAIN, LTD
300 S. WACKER DR.
SUITE 2500
CHICAGO, IL 60606
EXAMINER
GOUGH, TIFFANY MAUREEN
ART UNIT PAPER NUMBER
1651
NOTIFICATION DATE DELIVERY MODE
02/09/2017 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
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PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte CLAUDIA PACHOLSKI, GORDON M. MISKELLY, and
MICHAEL J. SAILOR1
Appeal 2015-007991
Application 12/683,895
Technology Center 1600
Before ERIC B. GRIMES, TIMOTHY G. MAJORS, and
RACHEL H. TOWNSEND, Administrative Patent Judges.
TOWNSEND, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35U.S.C. § 134 involving claims to a method
for biosensing, which have been rejected as anticipated and/or obvious. We
have jurisdiction under 35 U.S.C. § 6(b). We affirm-in-part.
STATEMENT OF THE CASE
Porous silicon microstructures have been used as biosensors to detect
analytes. (Spec. 2—3.) It is known that “[pjores can be tuned to trap a
particular analyte, for example based upon pore size or by preparing the
pores with a material to bind analyte.” {Id. at 2.)
1 Appellants identify the Real Party in Interest as The Regents of the
University of California. (Appeal Br. 2.)
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“Porous microstructures have been demonstrated to produce
characteristic spectral interference patterns.” {Id. at 1.) “Single layer porous
microstructures that are based on changes in the spectral interference pattern
have been used” in analyte detection. {Id. at 2.) Appellants’ Specification
indicates that “[ojthers have used multi-layer porous silicon to achieve
biosensors based on optical transduction methods other than wavelength
shifts of the interference pattern.” {Id.) Appellants’ invention is directed at
a method for biosensing using a multi-layer microporous thin film structure
where the top layer has larger pores than a second layer. {Id. at 3.)
Claims 1—13 are on appeal. Claims 1 and 5 are representative and
read as follows:
1. A method for biosensing, the method comprising:
exposing a biological analyte to a multi-layer micro-porous thin film
structure that has a top layer with larger pores than a second layer, the pores
being sized to produce multiple superimposed interference patterns that can
be resolved in the reflectivity spectrum;
exposing the multi-layer micro-porous thin film structure to light to
produce a reflectivity spectrum;
sensing the reflectivity spectrum to obtain reflectivity data;
extracting optical parameters from the reflectivity data;
determining, from the optical parameters, whether at least one
biomolecule of interest is present in said biological analyte.
5. The method of claim 1, wherein pores in the top layer are sized to
accept a first molecule of interest and pores in the second layer are sized to
accept a second molecule of interest that is smaller than the first molecule of
interest and to exclude the first molecule of interest from the second layer.
(Appeal Br. 18.)
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Application 12/683,895
The following grounds of rejection by the Examiner are before us on
review:
Claim 1 under 35 U.S.C. § 102(b) as anticipated over Zangooie.2
Claims 1—13 under 35 U.S.C. § 103(a) as unpatentable over Sailor I,3
Sailor II,4 Anglin,5 Zangooie, Allcock,6 Snow,7 and Ohkawa.8
DISCUSSION
Anticipation
The Examiner finds that Zangooie teaches a multi-layer micro-porous
thin film structure that has a top layer with larger pores than a second layer.
(Final Action 2—3; Ans. 2.) The Examiner further finds that Zangooie
teaches a method by which the thin film structure is used to determine the
presence of a biomolecule of interest in a biological material by exposing the
material to the multi-layer micro-porous thin film structure, exposing the
film to light, and determining, from optical parameters obtained from
2 S. Zangooie et al., Protein adsorption in thermally oxidized porous silicon
layers, 313—314 Thin Solid Films 825—830 (1998).
3 Sailor et al., US 2003/0146109 Al, published Aug. 7, 2003. (“Sailor I”)
4 Sailor et al., US 2005/0042764 Al, published Feb. 24, 2005. (“Sailor II”)
5 Emily J. Anglin et al., Engineering the Chemistry and Nanostructure of
Porous Silicon Fabry-Perot Films for Loading and Release of a Steroid, 20
Langmuir 11264—11269 (2004).
6 P. Allcock et al., Time-resolved sensing of organic vapors in low
modulating porous silicon dielectric mirrors, 90 J. Applied Physics (10)
5052-5057 (2001).
7 P. A. Snow et al., Vapor sensing using the optical properties ofporous
silicon Bragg mirrors, 86 J. Applied Physics (4) 1781—1784 (1999).
8 Makoto Ohkawa, US 6,645,045 B2, issued Nov. 11, 2003.
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reflectivity data obtained after exposing the thin film to light, whether at
least one biomolecule of interest is present. (Id.)
We agree with the Examiner’s factual findings and conclusion that the
method recited in claim 1 is anticipated by Zangooie. Zangooie describes
adsorption studies of samples of human serum albumin or fibrinogen in
phosphate buffered saline on multilayer porous silicon substrates. (Zangooie
826.)9 Zangooie notes that fibrinogen is a larger molecule than albumin.
(Id.) According to Zangooie, “protein adsorption is often reported to be
promoted at hydrophobic surfaces where more protein is adsorbed on these
surfaces compared with hydrophilic ones.” (Id. at 829.) In some of the
experiments, the multilayer microporous silicon substrate was first hydrated
“by immersion in a deionized water bath for 10 min.” and then “dried by
nitrogen, in order to desorb physically adsorbed water” prior to adding
biological material to the substrate, which created hydrophilic surfaces in the
outermost layer (layer 3) of the substrate. (Id. at 826—27, 829.) Zangooie
observed that for the albumin experiments on the hydrated substrate
adsorption of albumin in layer 2 increased, whereas it decreased in layer 3.
(See id. 828 Table 1 (providing results of “volume percentage of absorbed
albumin in PSD layers” of hydrated and non-hydrated substrate).) Zangooie
noted that “a lower interfacial free energy between the hydrated surfaces and
the solution causes a lower protein adsorption and shorter residence time in
layer 3 which increases the probability for a larger amount of protein
molecules to penetrate deeper in the porous layers resulting in a larger
9 Zangooie refers to the porous silicon dioxide substrate as “PSD samples”
or samples. (See, e.g., Zangooie 827.)
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volume percentage of albumin in layer 2 of the hydrated samples.” (Id. at
829.) Despite “the probability for a larger amount of protein molecules to
penetrate deeper in the porous layers” of a hydrated substrate, Zangooie
noted that no fibrinogen was found in layer 2, whether the substrate was
hydrated or not. (Id. at 828 (Table 2: reporting “Volume percentage of
absorbed fibrinogen in PSD layers” and noting percentages found only in
layer 3); id. at 829 (noting that “[cjhanges in hydrophilicity obtained by
hydration was not sufficient enough to affect the amount of adsorbed
fibrinogen as it did with albumin.”).) Zangooie, thus, notes that protein
adsorption in the layers “is also a function of molecular size, since no
fibrinogen is found in layer 2.” (Id. )
In light of the foregoing, we find the Examiner’s conclusion that the
pore size in the outermost layer (3) of the Zangooie multilayer porous silicon
substrate has larger pores than the layer below it (layer 2) is supported by a
preponderance of evidence. We do not find Appellants’ contrary arguments
persuasive. (Appeal Br. 4—7.)
In particular, we do not agree with Appellants that Zangooie teaches
hydration alone was responsible for exclusion of fibrinogen in the lower
layer (Appeal Br. 5; Reply Br. 2). As noted above, whether or not the
substrate was hydrated, fibrinogen was not determined to adsorb in layer 2.
(See e.g., Zangooie 829 (noting no fibrinogen found in layer 2 regardless of
whether the sample was hydrated); see also Zangooie 828 (compare Table 1
with Table 2: noting volume percentage of adsorbed fibrinogen in Layer 3
with no identification of any protein found in a Layer 2) and 825 (abstract
stating: “Hydration did not, however, affect the adsorption behavior of
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fibrinogen which was found to adsorb only in the outermost sublayer. This
phenomenon was attributed to the larger size of this protein.”).)
We also disagree with the argument that Zangooie provides “[m]ere
recognition that different molecules (albumin and fibrinogen) absorb
differently into Zangooie’s porous structure due to hydration” (Appeal Br. 5
(emphasis added)). While hydration was shown to affect adsorption of
different molecules differently, pore size was demonstrated to have an effect
on adsorption. Indeed, even the Declaration of inventor Sailor10 recognizes
that Zangooie implicates that pore size affects adsorption. (Sailor Dec. 14
(noting that the assertion that:
“adsorption of proteins of different sizes provides us with a rough
estimate of the pore sizes in different sublayers of the material.”
P829, right column . . . implies that the different layers in each film
under study possess[] different pore sizes.)
Zangooie specifically notes that “spectroscopic ellipsometry and the
optical models provide us with new opportunities to obtain a rough estimate
of the pore size distribution in the porous films by means of adsorption of
proteins of different sizes.” (Zangooie 829.) As discussed, supra, in
Zangooie, albumin, the smaller sized compound as compared to fibrinogen,
was observed in layers 3 and 2, whether or not the substrate was hydrated,
while fibrinogen was only observed in layer 3, whether or not the substrate
was hydrated. Whether stated or not, and regardless of the fact that porosity
and pore size may be different things (Reply Br. 3), the Zangooie
10 The Declaration is dated April 11, 2014.
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experiments demonstrated, with respect to pore size distribution in the films
used in the experiments, that layer 3 included larger pore sizes than layer 2.
Whether or not Zangooie planned or controlled the pore sizes in the
different layers to obtain the resultant film that had layer 3 with larger pore
sizes than layer 2 (Sailor Dec. 1411; Appeal Br. 6—7; Reply Br. 3) is not
decisive. Provided a prior art reference discloses every claim limitation, that
reference anticipates under 35 U.S.C. § 102(b). In re Montgomery, 677
F. 3d 1375, 1379 (Fed. Cir. 2012). For the reasons discussed, the structure
of the film used in the experiments of Zangooie necessarily had the claimed
“top layer with larger pores than a second layer” (Ans. 12). And there is no
dispute by Appellants that the following was described as having been
carried out in the prior art (1) the claimed steps of exposing the biological
sample to a multi-layer microporous thin film structure or (2) the steps of
exposing the structure to light and determining, from the optical parameters
from the reflectivity data obtained, whether a biomolecule of interest is
11 In somewhat of a non-sequitor, while discussing that Zangooie does not
imply an ability to predetermine pore size to achieve size exclusion from a
layer, Sailor also states that “in Zangooie, hydration is proposed to exclude
fibrinogen from layer 2.” (Sailor Dec. 14.) We do not read Zangooie to
demonstrate fibrinogen is excluded from layer 2 because of hydration. In
the first place, hydration is noted to inhibit adsorption of albumin in layer
3—the outer most layer—,not layer 2, due to the more hydrophilic hydrated
surfaces in layer 3. Secondly, regarding fibrinogen, as noted, supra,
Zangooie notes that hydration did not “affect the amount of adsorbed
fibrinogen [as to layer 2] as it did with albumin” where “a larger volume
percentage of albumin in layer 2 of the hydrated samples” was found as
compared to non-hydrated samples. (Zangooie 829; see also 828 Tables 1
and 2.)
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present in the sample. Thus, for the reasons discussed, Appellants do not
persuade us that the Examiner erred in rejecting claim 1 for anticipation over
Zangooie.
Obviousness: claims 1, 5, and 12
The Examiner finds that Sailor I, Sailor II, and Anglin teach “multi­
layer porous thin film structures having different or tunable pore sizes for
biosensing molecules of interest and obtaining reflectivity spectra and
interference patterns were known and disclosed by the prior art of record.”
(Ans. 16—17; Final Action 5—9.) In particular, the Examiner finds Sailor I
teaches a porous silicon structure comprising varying pore sizes wherein the
light reflected from the structure produces interference patterns, and that this
device can be used for biological molecule sensing. (Final Action 5.) The
Examiner further finds that Sailor I teaches that “one can tune pore
diameters and modify the surface to control the size and type of molecules
adsorbed (0043) for sensitive detection of analytes.” (Id.)
The Examiner finds that Sailor II teaches
exposing a biological analyte to a multi-layer micro-porous thin
film structure that has a top layer with a different porosity than
the second layer (fig. 1), the porosity being sized to produce
multiple superimposed interference patterns that can be
resolved in the reflectivity spectrum.
(Final Action 6.) The Examiner finds that Sailor II “teaches that the
variance in porosities between layers permits the tailoring of optical
signatures in the reflectivity spectrum.” (Id.) The Examiner finds, in
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addition, that Sailor II teaches “computing a fast Fourier transform of the
reflective spectrum and determining position and amplitude shifts.” (Id.)
The Examiner finds that Anglin teaches “computing a Fast Fourier
transform of reflectivity spectrums from optical parameters in porous thin
films of varying pore sizes to determine loading of an analyte.” (Final
Action 6.) The Examiner further finds Anglin teaches “that porous Si has
tunable pore sizes and allows optical reporting on molecule loading,” and
“how to adjust the pore sizes.” (Final Action 7.)
The Examiner recognizes that Sailor I, Sailor II, and Anglin do not
teach that the top layer of the film has larger pores than the second layer.
The Examiner notes however, that Zangooie teaches such a multi-layer
micro-porous thin film structure. (Final Action 7.)
The Examiner finds that “the art clearly suggest that porous thin films
can be manipulated to obtain the desired pore sizes in a multi-layer film and
said films are known to be used to obtain optical parameters of molecules
within the pore layers,” “teaches advantages of pore variance to affect
refractive index and interference patterns” (Final Action 8; Ans. 17), and
“demonstrates a top layer having larger pores than the second layer” (Ans.
17). Thus, the Examiner determines it would have been obvious to one of
ordinary skill in the art to manipulate porous thin films to obtain desired
pore sizes in different layers in light of the prior art and to use a multi-layer
porous silicon film in which the top layer has larger pores than the second
layer. (Final Action 8; Ans. 17.)12
12 We note that the Examiner’s rejection of claims 1, 5, and 12 only relies on
Sailor I, Sailor II, Anglin, and Zangooie. The rejection of dependent claim 7
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We agree with the Examiner’s finding that it would have been
obvious to provide a multilayer porous thin film where the top layer has
larger pores than the second layer as required in claims 1,5, and 12. As
discussed above, and contrary to Appellants’ position (Appeal Br. 8),
Zangooie teaches a multilayer microporous film that has such a structure,
whether intentionally made or not. Zangooie demonstrates that a small pore
size can preclude adsorption of proteins in a lower layer of a multilayer
microporous thin film. We agree that it would have been obvious to use
such a structure (which would have pores in the second layer sized to
exclude a biological molecule of a particular size but be able to accept
another smaller biological molecule) in the methods of Sailor I and II
thereby providing a structure that would provide for the ability to determine
the presence of a biomolecule of interest. Moreover, such a structure would
be able to distinguish between “filling of pores in the top layer and in the
second layer” based on differences in interference reflectivity spectrum
sensed, as demonstrated in Zangooie where filling of pores in the second
layer was determined not to occur with fibrinogen but filling of pores in the
first layer was determined to have occurred.
Appellants’ arguments that the art does not teach or suggest the
“providing” step of claims 12 and 5, because it does not suggest “the
combined selection and exclusion of first and second molecules via pore
size” and “does not suggest any ability to selectively distinguish between
first and second molecules of interest” (Appeal Br. 9—10) is also unavailing.
relies on the additional teachings of Allcock, Snow, and Ohkawa. (Final
Action 9—10.)
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Zangooie’s teaching that a larger molecule is excluded from adsorption in
the second layer because of its size provides the suggestion in combination
with Sailor I’s teaching of using thin layer microporous film for identifying
more than one analyte from a sample (Sailor I abstract).
Appellants argue that “the large number multi-reference rejection”
evidences improper hindsight. (Appeal Br. 7; see also Appeal Br. 14.) We
disagree. A reliance on a large number of references in a rejection does not,
without more, weigh against the obviousness of the claimed invention. See
In re Gorman, 933 F.2d 982, 986 (Fed. Cir. 1991). As explained above, the
prior art teaches that pore size can be “tuned” to a particular size, and that
differences in porosity and pore size between layers can provide tailoring of
the reflectivity spectrum. The Examiner’s rejection relies on these teachings
to support the obviousness of substituting the structure of Zangooie into
either or both of the Sailor references that teach the use of microporous thin
film sensors to detect biological material and to do so with a reasonable
expectation of success and, thus, meet the limitations of claims 1, 5, and 12.
Appellants contend that there is no evidence of an expectation of
success with respect to claims 5 and 12 in being able to “separately
distinguish between first and second molecules of interest” by observing
interference patterns “consisting of a sensed top layer component, a sensed
second layer component and a sensed top plus second layer component.”
(Appeal Br. 12—13.) We note that neither of claims 5 or 12 require
separately distinguishing “between first and second molecules of interest” by
analysis of the interference patterns, but rather, simply require distinguishing
between filling of pores in the top layer and in the second layer. Zangooie
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teaches this when it determines that no fibrinogen is present in the second
layer but is present in the top layer. In any event, we agree with the
Examiner that Sailor II’s teaching that “the refractive index at layer
interfaces affects the optical signature generated by the particles and, thus,
varying porosity between layers permits the tailoring of optical signatures in
the reflectivity spectrum (0022).” (Ans. 21.) And, because pore size and
porosity are related, we agree that one of ordinary skill in the art would have
had a reasonable expectation of success in using the optical measuring
taught by Sailor (and Anglin) with the Zangooie microporous structure to
distinguish the analytes in the top layer and the second layer. (Id.)
“Obviousness does not require absolute predictability of success. . . . For
obviousness under § 103, all that is required is a reasonable expectation of
success.” In re O’Farrell, 853 F.2d 894, 903-04 (Fed. Cir. 1988).
We also disagree with Appellants that the Examiner’s rejection does
not put them on notice of what references were applied to what claims. The
Examiner identified the elements of Appellants’ claims (see, e.g., Final
Action 5) and identified what element of the claims was missing from
particular references discussed, (see, e.g., Final Action 7 (noting that Sailor
I, II and Anglin do “not teach the top layer to have larger pore sizes than the
second layer”); Final Action 9 (referring specifically to the equation recited
by claim 7)) and then identified why the limitation would have been obvious
in light of the teachings of other prior art references. We conclude that the
Examiner’s rejection meets the standard required by 35 U.S.C. § 132. See In
re Jung, 637 F.3d 1356, 1363 (Fed. Cir. 2011) (“[A]ll that is required of the
office to meet its prima facie burden of production is to set forth the
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statutory basis of the rejection and the reference or references relied upon in
a sufficiently articulate and informative manner as to meet the notice
requirement of § 132.”).
Claims 2—4, 6, and 13 have not been argued separately and therefore,
fall with claims 1, 5, and 12. 37 C.F.R. § 41.37(c)(l)(iv).
Obviousness: Claim 7
The Examiner contends that Ohkawa, Allcock, and Snow disclose
methods and equations for measuring the reflectivity spectra of
porous silicon films having more than one layer and different
sized pores. Snow teaches equations 2 and 3 which teach
variables for obtaining reflectivity spectrums. Ohkawa teach[es]
Equation D and P corresponding to that of applicants!”] claim 7,
Eq.2.
(Final Action 10.) According to the Examiner, “it would have been obvious
to one of ordinary skill in the art to combine the variables in a different way
as in the equation in Claim 7,” noting that “[t]he analysis of two layers
follows a similar mathematical treatment to a single layer.”
We disagree with the Examiner that the method of claim 7 is rendered
obvious by the cited references. The Examiner has not established why one
of ordinary skill would have selected the exact combination of parameters,
with the specified relationships, set forth by claim 7’s equation as a whole.
As Appellants note “[i]t is not a fair application of obviousness to conclude
that variables concerning Bragg stacks would have rendered the model and
method of claim 7 obvious, as it does not concern a Bragg stack.” (Appeal
Br. 14.)
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SUMMARY
We affirm the rejection of claim 1 under 35 U.S.C. § 102(b) as
anticipated over Zangooie.
We affirm the rejection of claims 1—6, 12, and 13 under 35 U.S.C.
§ 103(a) as unpatentable over Sailor I, Sailor II, Anglin, and Zangooie.
We reverse the rejection of claims 7—11 under 35 U.S.C. § 103(a) as
unpatentable over Sailor I, Sailor II, Anglin, Zangooie, Allcock, Snow, and
Ohkawa.
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).
AFFIRMED-IN-PART
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