Ex Parte Charych et al

Board of Patent Appeals and Interferences

Nov 8, 2007

09874091 (B.P.A.I. Nov. 8, 2007)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte DEBORAH CHARYCH, ERIC BEAUSOLEIL,
and RONALD N. ZUCKERMANN
__________

Appeal 2007-2723
Application 09/874,091
Technology Center 1600
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Decided: November 8, 2007
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Before ERIC B. GRIMES, RICHARD M. LEBOVITZ, and FRANCISCO
C. PRATS, Administrative Patent Judges.

PRATS, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to an array
of protein binding agents attached to a solid support. The Examiner has
rejected the claims as obvious. We have jurisdiction under 35 U.S.C. § 6(b).
We reverse.
BACKGROUND
“In recent years, microarray technology has developed from a
specialized sub-field into an important tool for basic and applied studies in
molecular biology, microbiology, pharmaceutics, agriculture, and many
Appeal 2007-2723
Application 09/874,091

other biotechnologies. DNA microarray technology attempts to link the
genome of an organism or cell to an expressed phenotype or protein
function” (Specification 1).
However, using DNA microarrays to evaluate a cell can be
problematic because, “[i]n many cases, functional pathways cannot be
directly linked to a particular gene. Proteins often undergo a variety of post-
translational modifications, interactions, or degradations that ultimately
determine function” (id. at 2). Thus, “[e]ven the seemingly simple
evaluation of a protein's abundance cannot be directly correlated with the
level of corresponding mRNA. The only solution is to evaluate the state of
the cell, tissue or organism at the protein level” (id.).
DISCUSSION
1. CLAIMS
Claims 1, 60-73, 79-91, and 97-101 are pending and on appeal
(Appeal Br. 1). Claims 1 and 73, the two appealed independent claims, are
representative and read as follows:

1. An array of protein-binding agents stably attached to the
surface of a solid support, said array comprising:
a solid substrate having a substantially planar surface
comprising a layer of aluminum formed on a glass base
material, the aluminum coated with a silicon dioxide coating
having a thickness of between about 200 and 900Å;
a plurality of different protein-binding agents bound to
said substrate, each of said protein-binding agents comprising,
an anchoring segment stably bound to the substrate
surface,
a peptidomimetic protein-binding segment, and
a linker segment connecting and separating the anchoring
and peptidomimetic segments.
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73. A kit for use in performing a differential binding assay,
said kit comprising:
an array comprising
a solid substrate having a substantially planar
surface comprising a layer of aluminum formed on a
glass base material, the aluminum coated with a silicon
dioxide coating having a thickness of between about 200
and 900 Å;
a plurality of different protein-binding agents
bound to said substrate, each of said protein-binding
agents comprising,
an anchoring segment stably bound to the substrate
surface,
a peptidomimetic protein-binding segment, and
a linker segment connecting and separating the
anchoring and peptidomimetic segments;
one or more reagents for conducting a differential
binding assay comprising a plurality of fluorescent labels
for proteins.

2. PRIOR ART
The Examiner relies on the following references:
Gustafson US 5,478,527 Dec. 26, 1995
Barrett US 5,482,867 Jan. 9, 1996
Chenchik US 6,087,102 Jul. 11, 2000
Wagner US 6,329,209 B1 Dec. 11, 2001

3. OBVIOUSNESS -- GUSTAFSON AND CHENCHIK
Claims 1, 60, 61, 63-66, 73, 79, 80, 82-85, and 97-101 stand rejected
under 35 U.S.C. § 103 as obvious in view of Gustafson and Chenchik
(Answer 3-6, 13-16).
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The Examiner cites Gustafson as teaching a “biograting” that
comprises protein binding agents attached in a patterned arrangement to a
wafer composed of glass, aluminum, and silicon dioxide layers that meet the
limitations recited in claim 1 (id. at 3-4). With respect to claim 1 and its
dependents, the Examiner states that “[t]he array of Gustafson et al. differs
from the presently claimed invention by failing to include a plurality of
fluorescent labeled proteins” (id. at 4). With respect to claim 73 and its
dependents, the Examiner states that Gustafson “differs from the presently
claimed invention by failing to include packaging the array into a kit format
that includes a label[ed] reagent” (id. at 14).
The Examiner cites Chenchik to meet those limitations (id. at 4-5, 14-
15). The Examiner finds that persons of ordinary skill in the art would have
been motivated to incorporate Chenchik’s plurality of fluorescently labeled
proteins into Gustafson’s array “for the advantage of providing a high
throughput format that provides two types of informations, which are the
types of genes expressed and the size of the expressed products[,] since both
Gustafson et al. and Chenchik et al. disclose an array of polymeric
compounds such as proteins” (id. at 5, citations omitted). The Examiner
finds that the same rationale would have encouraged one of ordinary skill to
package Gustafson’s assay product in a kit having a plurality of
fluorescently labeled proteins (id. at 15).
Appellants argue that the combination of references advanced by the
Examiner would not have rendered the claims obvious because “Gustafson
relates to such fundamentally different arrays and assay techniques than both
Chenchik and the claimed invention that one of skill would not arrive at the
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claimed invention from the combination of Gustafson and Chenchik”
(Br. 7-8).
In proceedings before the Patent and Trademark Office,
the Examiner bears the burden of establishing a prima facie
case of obviousness based upon the prior art. “[The Examiner]
can satisfy this burden only by showing some objective
teaching in the prior art or that knowledge generally available to
one of ordinary skill in the art would lead that individual to
combine the relevant teachings of the references.”

In re Fritch, 972 F.2d 1260, 1265 (Fed. Cir. 1992) (citations omitted,
bracketed material in original). Thus, as recently pointed out by the
Supreme Court, “a patent composed of several elements is not proved
obvious merely by demonstrating that each of its elements was,
independently, known in the prior art.” KSR Int'l v. Teleflex Inc., 127 S. Ct.
1727, 1741 (2007). Rather, “[t]he test for obviousness is what the combined
teachings of the references would have suggested to one of ordinary skill in
the art.” In re Young, 927 F.2d 588, 591 (Fed. Cir. 1991).
We agree with Appellants that the Examiner has not established that
the teachings of Gustafson and Chenchik would have led one of ordinary
skill to practice the subject matter recited in the rejected claims.
Specifically, the only difference between Gustafson and claim 1
acknowledged by the Examiner is Gustafson’s “fail[ure] to include a
plurality of fluorescent labeled proteins” (Answer 4). With respect to claim
73, the only difference acknowledged by the Examiner is that Gustafson
“fail[s] to include packaging the array into a kit format that includes a
label[ed] reagent” (id. at 14). However, claims 1 and 73 both require “a
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plurality of different protein-binding agents” (emphasis added) to be bound
to the claimed array’s substrate.
We do not see, and the Examiner does not explain, where Gustafson
discloses or suggests a substrate having a plurality of different
protein-binding agents. Specifically, Gustafson discloses a “biograting,”
which is a flat surface coated with “a diffraction grating pattern of
alternating and preferably parallel linear zones of an active and deactivated
binding reagent. The zones form a diffraction grating when the active
binding reagent binds with its opposite member of the binding pair”
(Gustafson, col. 3, ll. 60-64; see also Figure 1). Thus, when a target analyte
present in a sample binds to the substrate-bound protein binding agent “the
accumulation of bound material in the patterns of a diffraction grating
creates a light disturbing grating, and light detected at the light diffraction
angles increases to a large value which correlates to the presence and
quantity of the binding partner (analyte) in the sample” (id. at col. 3, l. 67,
through col. 4, l. 5). In contrast, because a sample lacking the target analyte
will contain nothing that can bind to the substrate-bound active binding
reagent, “no significant light diffraction occurs, that is, light energy detected
at the diffraction angles is at a minimum value, approaching zero” (id. at col.
3, ll. 64-67).
Thus, Gustafson’s substrate contains only a single type of protein
binding agent attached to it in a pattern that, when bound with a protein
binding partner, diffracts light in a manner that allows for detection and
quantification of a target analyte (id. at col. 3, l. 56 through col. 4, l. 5). We
therefore agree with Appellants that Gustafson does not describe how to use
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its grating with different protein binding partners (Appeal Br. 10). To the
contrary, “the entire context of Gustafson is premised on a single target
bound on a substrate densely enough to form parallel lines that will diffract
incident light when bound to its analyte partner” (id.).
To reflect sufficient light to evaluate the light diffraction, Gustafson
discloses that the underlying substrate should have a “reflective [] layer . . .
supported on an optically flat surface of a wafer, and the reflective metal can
be aluminum” (id. at col. 2, ll. 44-46). A layer of silicon dioxide, to which
the protein binding agent will be attached, is “[p]referably . . . formed by
sputtering a thin layer of silicon dioxide or by coating an alkali metal silicate
solution on the surface of the reflective metal” (id. at col. 2, ll. 48-50).
Therefore, to the extent that Gustafson discloses or suggests a substrate
meeting the structural limitations in claims 1 and 73, Gustafson also
discloses that that substrate is designed to reflect light in a manner such that
a single analyte bound to the substrate in a patterned arrangement will
diffract light in a detectable and quantifiable manner.
Unlike Gustafson, Chenchik is not directed to detecting a single
analyte based on the light diffraction that results when the analyte binds to a
patterned substrate-bound binding partner. Instead, Chenchik uses
fluorescently labeled proteins to determine when binding has occurred
between one of the arrays’ different substrate-bound protein-binding agents
and its partner (see Chenchik, col. 8, l. 55, through col. 11, l. 24).
Because Chenchik’s fluorescence-based detection techniques do not
rely on light diffraction to detect the presence of a target analyte, we agree
with Appellants that one of ordinary skill would not have looked to
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Gustafson’s diffraction-generating biograting substrate as a support for
Chenchik’s protein-binding arrays. We also agree with Appellants that,
because Gustafson discloses that the detectable light diffraction requires a
single analyte to be bound to the substrate in a specific pattern, one of
ordinary skill would not have considered it obvious to attach a plurality of
different protein-binding agents to Gustafson’s substrate.
Therefore, because the Examiner has not shown that persons of
ordinary skill in the art would have been prompted to attach a plurality of
different protein-binding agents to a substrate having the claimed
glass/aluminum/silicon dioxide configuration, we reverse the Examiner’s
obviousness rejections of claims 1 and 73, and their dependent claims.
4. OBVIOUSNESS -- GUSTAFSON, CHENCHIK, AND WAGNER
Claims 62 and 81 stand rejected under 35 U.S.C. § 103 as obvious
over Gustafson, Chenchik, and Wagner (Answer 6-10, 16-20).
Claim 62, ultimately depending from claim 1, limits the array of claim
1 to one having a maleimide-functionalized aminosilane between the silicon
oxide layer and the protein binding agents. Claim 81, ultimately depending
from claim 73, limits the array in the kit of claim 73 to one having the same
maleimide-functionalized aminosilane linkage between the silicon oxide
layer and the protein binding agents.
The Examiner concedes that Gustafson and Chenchik do not disclose
an array having the feature recited in claims 62 and 81, and cites Wagner to
meet that limitation (Answer, 8-9, 18-19). We reverse this rejection as well.
As discussed above, we do not agree with the Examiner that one of ordinary
skill would have considered the arrays recited in claims 1 and 73 obvious in
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view of Gustafson and Chenchik. We do not see, and the Examiner does
not point to, any disclosures in Wagner that remedy the shortcomings of the
other references.
We therefore reverse the Examiner’s rejections of claims 62 and 81.
5. OBVIOUSNESS -- GUSTAFSON, CHENCHIK, AND BARRETT
Claims 67-72 and 86-91 stand rejected under 35 U.S.C. § 103 as
obvious over Gustafson, Chenchik, and Barrett (Answer 10-13, 20-23).
Claim 67, ultimately depending from claim 1, limits the array of claim
1 to one having an avidin-functionalized aminosilane between the silicon
oxide layer and the protein binding agents. Claim 68 depends from claim
67, and limits the array’s anchoring segment to biotin. Claims 71, 72, 86,
87, 90, and 91 contain similar limitations. The Examiner concedes that
Gustafson and Chenchik do not disclose an array having the features recited
in the rejected claims, and cites Barrett to meet those limitations (Answer,
12-13, 22-23). We reverse this rejection as well.
We first note that claims 69, 70, 88, and 89 do not recite the
avidin-biotin linkage which the Examiner cites as being disclosed by Barrett.
Rather, those claims appear to recite the maleimide-derivatized aminosilane
for which the Examiner cited the Wagner reference. Thus, the references
cited by the Examiner do not appear to disclose all of the limitations of the
claims included in this ground of rejection.
Moreover, as discussed above, we do not agree with the Examiner that
one of ordinary skill would have considered the arrays recited in claims 1
and 73 obvious in view of Gustafson and Chenchik. Because we do not see,
and the Examiner does not point to, any disclosures in Barrett that remedy
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the shortcomings of the other references, we reverse the Examiner’s
obviousness rejections of claims 67-72 and 86-91.
SUMMARY
We reverse the Examiner’s obviousness rejections of claims 1, 60-73,
79-91, and 97-101.

REVERSED
LP
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