Ex Parte Becker et al

Board of Patent Appeals and Interferences

Jan 31, 2003

09163572 (B.P.A.I. Jan. 31, 2003)

The opinion in support of the decision being entered today was not written
for publication and is not binding precedent of the Board.

Paper No. 20

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte KATHERINE BECKER and
JOHN SCOTT
__________

Appeal No. 2001-0692
Application No. 09/163,572
__________

ON BRIEF
__________

Before ADAMS, GRIMES, and GREEN, Administrative Patent Judges.

GRIMES, Administrative Patent Judge.

DECISION ON APPEAL

This is a decision on appeal under 35 U.S.C. § 134 from the examiner’s
final rejection of claims 1-4, 8-10, 13-33, 36, and 37, all of the claims remaining.
Claims 1, 9, and 23 are representative and read as follows:
1. A method of simultaneously testing a plurality of compounds for
activity in a screen which is a biological assay to determine the
biological activity of the compounds comprising the steps of:

(a) placing a plurality of the compounds into at least two arrays,
each having a plurality of test zones, with multiple
compounds in each zone and at least one identical
compound in at least two arrays;

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(b) determining the array location of each compound in each
test zone;

(c) determining the response activity of the compounds in the
arrays to the testing screen; and

(d) ascertaining the compounds that had a positive response to
the testing screen.

9. The method of claim 1 wherein the activity is the ability of
compounds to hybridize to a library of genes.

23. The method of claim 1 wherein the activity is to determine a
cholesteryl ester transfer protein inhibitor.

The examiner relies on the following references:
Pomponi et al. (Pomponi) 5,446,207 Aug. 29, 1995
Evans et al. (Evans), “Physical mapping of complex genomes by cosmid
multiplex analysis,” Proc. Natl. Acad. Sci. USA, Vol. 86, pp. 5030-5034 (1989)

Claims 1-4 and 9 stand rejected under 35 U.S.C. § 102(b) as anticipated
by Evans.
Claims 8, 10, 13-33, 36, and 37 stand rejected under 35 U.S.C. § 103 as
obvious in view of Evans and Pomponi.
Claims 1-4, 8-10, 13-33, 36, and 37 stand rejected under 35 U.S.C. § 112,
second paragraph, as indefinite.
We affirm the rejection for anticipation but reverse the rejections for
obviousness and indefiniteness.
Background
The specification discloses a method of simultaneously testing a large
number of compounds in a biological assay. The disclosed method starts with a
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set of “simple plates” which each contain test compounds arranged in a row-and-
column grid. See page 5, lines 6-12. Thus, for example, a set of 10 simple
plates might each contain a grid made up of 10 columns and 8 rows (80 test
compounds per plate, or 800 test compounds in the set of 10 simple plates). See
id.
The compounds on the set of simple plates are combined to produce two
“master plates,” known as the X master plate and the Y master plate. See page
5, lines 12-22. To produce the X master plate, samples of each compound in a
specific row of a specific plate are combined into a single, specific well in the X
plate. Thus, for example, the first well of the first column of the X plate would
contain a sample of each compound from columns 1 through 10 in the first row of
plate 1, the second well in the first column of the X plate would contain a sample
of each compound from the second row of plate 1, and so on. In this way, the
contents of each simple plate are represented in a specific column of the X
master plate.
The Y master plate is produced by a different method. The Y master plate
is produced by taking a sample from the same location on each simple plate, and
combining these ten samples into a single well in the same location on the Y
plate. Thus, for example, samples of the compound found in the first column of
the first row of each of the ten simple plates are combined in the well in the first
column of the first row of the Y master plate. Thus, “[b]oth the ‘X Master plate’
and the ‘Y Master plate’ have 10 compounds in each well while each compound
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appears once on each plate. However, no two compounds have the same pair of
well locations.” Id., page 7.
After the X and Y master plates are produced, they are subjected to any of
a variety of biological assays. See, e.g., pages 25-28. The pattern of positively
reacting samples on the X and Y master plates identifies a specific compound or
set of compounds as having positive activity in the screen.
Visually, when a hit is observed at a well in the Y plate, one can
conclude that the hit resulted due to an active compound located at
the same well location in one of the ten simple plates. A hit in the
same row of the X plate can then be used to determine which of the
ten simple plates contains the active compound. Specifically, the
column number of the hit represents the simple plate which
contains the active compound.

Specification, page 18.
The advantage of this, even given the probability of testing inactive
compounds, is that the biological testers can go directly to
quantitative screening with individual compounds. There is no
need to create plates that contain the individual compounds. The
same plate pairs can be sent to multiple screens, without need to
create differently arranged plates for each screen.

Id., page 8.
Discussion
1. Indefiniteness
The examiner rejected all of the claims as indefinite. See the Examiner’s
Answer, page 7:
The preamble of claim 1 is directed to testing for activity but the
claim lacks any such step. In view of claim 1 directed to activity,
the dependent claims are not directed to activity where claims 8, 9,
13 are directed to ability, claims 14, 16 are directed to presence,
claims 15, 17 are directed to absence, and so forth.

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As amended, claim 1 now reads on determining the response
activity which is not understood. Compounds may have a response
to some reaction or an activity but not a response activity. Further,
step 1(d) is directed to a positive response where this is not an
activity and is not understood in context. The determination of
whether a reaction takes place or does not is not presently claimed.

“The definiteness of the language employed must be analyzed—not in a
vacuum, but always in light of the teachings of the prior art and of the particular
application disclosure as it would be interpreted by one possessing the ordinary
level of skill in the pertinent art.” In re Moore, 439 F.2d 1232, 1235, 169 USPQ
236, 238 (CCPA 1971). “The purpose of claims is not to explain the technology
or how it works, but to state the legal boundaries of the patent grant. A claim is
not ‘indefinite’ simply because it is hard to understand when viewed without
benefit of the specification.” S3 Incorporated v. NVidia Corp., 259 F.3d 1364,
1369, 59 USPQ2d 1745, 1748 (Fed. Cir. 2001).
We do not find the claims to be indefinite. The claim language, when read
in light of the specification, would be readily understood by those skilled in the
art. See Hybritech, Inc. v. Monoclonal Antibodies, Inc., 802 F.2d 1367, 1385,
231 USPQ 81, 94-95 (Fed. Cir. 1987) (Claims comply with 35 U.S.C. § 112,
second paragraph, if “the claims, read in light of the specification, reasonably
apprise those skilled in the art and are as precise as the subject matter
permits.”). The rejection under 35 U.S.C. § 112, first paragraph, is reversed.
2. Anticipation
The examiner rejected claims 1-4 and 9 under 35 U.S.C. § 102(b) as
anticipated by Evans. The examiner noted that Evans “teaches on page 5032
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Fig. 2 multiwell plate grids with a single clone common to both plates.”
Examiner’s Answer, page 4. See also page 8: “It is the examiner’s position that
Evans teaches the presently claimed method of testing a plurality of compounds
for activity. In the wells of Evans, a plurality of compounds is added and their
activity is determined, all simultaneously. Note that the reaction of a probe being
positive or negative is an activity determination.”
“It is well settled that a claim is anticipated if each and every limitation is
found either expressly or inherently in a single prior art reference.” Celeritas
Techs. Ltd. v. Rockwell Int’l Corp., 150 F.3d 1354, 1361, 47 USPQ2d 1516, 1522
(Fed. Cir. 1998). “[T]he description of a single embodiment of broadly described
subject matter constitutes a description of the invention for anticipation
purposes.” In re Lukach, 442 F.2d 967, 970, 169 USPQ 795, 797 (CCPA 1971).
We agree with the examiner that Evans anticipates instant claim 1. Claim
1 is directed to a screening method in which a plurality of test compounds are
placed into at least two arrays, each of which has a plurality of test zones;
multiple compounds are placed into each test zone, and at least one identical
compound is placed into each of the two arrays. After the test compounds are
placed into the arrays, the claimed method entails determining the location of
each compound in the test zones of each array, determining the response activity
of the compounds to the testing screen, and ascertaining which compounds had
a positive response to the testing screen.
In the method disclosed by Evans, different DNA molecules (cosmids) are
“organized as an ordered matrix.” Abstract; see also Figure 2. All of the cosmids
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in a particular row or column of the array are then used to generate DNA probes
corresponding to part of the DNA in each cosmid. See the legend to Figure 2.
The pooled probes are then applied to all of the cosmids in the array and
cosmids that hybridize to one of the mixed probes are identified. When the
results of hybridization to a particular row and column are compared, cosmids
that hybridize to both sets of mixed probes are identified as having DNA
sequence that overlaps the DNA sequence of the cosmid clone that is common
to both sets of probes. For example, in Evans’ Figure 2, the mixed probes
corresponded to the second row of the matrix (in the left-hand plate) and the
fourth column of the matrix (in the right-hand plate). A single cosmid (marked
with an arrow) hybridized to both sets of mixed probes. Thus, this cosmid was
identified as containing a DNA sequence that overlapped the DNA sequence of
the cosmid common to both probe sets, i.e., the cosmid located in the second
row, fourth column.
This method meets all of the limitations of instant claim 1, including any
limitations arising out of the claim’s preamble. Claim 1 is directed to a method of
“simultaneously testing a plurality of compounds for activity in a screen which is a
biological assay to determine the biological activity of the compounds.” Claim 9
makes clear that such activities include “the ability of compounds to hybridize to
a library of genes.” Evans discloses a method of simultaneously testing a
plurality of nucleic acid probes for the ability to hybridize to a library of cloned
DNA segments, which would be expected to include genes.
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The manipulative steps recited in claim 1 are also met by Evans:
(1) “placing a plurality of the compounds into at least two arrays”: Evans
places mixed probes into two arrays (see Figure 2);

(2) arrays having a plurality of test zones: each of the immobilized
cosmids constitutes a separate test zone;

(3) “multiple compounds in each zone”: Evans’ method includes applying
mixed probes (i.e., a mixture of probes generated from each of
approximately 20 different cosmids) to each test zone in a matrix;

(4) “at least one identical compound in at least two arrays”: the
experiment described in Evans’ Figure 2 involves applying the probe
generated from the cosmid at row 2, column 4 to each of the two
arrays; it is the hybridization of this probe to the cosmid marked with an
arrow that identifies that cosmid as sharing sequence identity with the
row 2, column 4 cosmid;

(5) “determining the array location of each compound in each test zone”:
in Evans’ technique the same set of compounds is applied to every test
zone in a given array;

(6) “determining the response activity of the compounds in the arrays to
the testing screen”: Evans determines hybridization of the probes with
the immobilized cosmid DNA; and

(7) “ascertaining the compounds that had a positive response to the
testing screen”: the hybridizing cosmids are identified.

Thus, we conclude that Evans identically discloses all of the limitations of
claim 1. Claim 1 is therefore anticipated. Appellants have grouped claims 1-4
and 9 together on appeal. See the Appeal Brief, page 4. Therefore, claims 2-4
and 9 fall with claim 1.
Appellants argue that “[t]hroughout the specification, Applicant [sic] has
indicated that the invention pertains to screening of large databases of
compounds.” Appeal Brief, page 5. Evans, by contrast, “does not have and
does not teach a testing of known compounds in a drug screening process. . . .
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Application No. 09/163,572

[In Evans], the libraries were not known nor [were] the RNA probes known at the
time the testing was performed. Clearly this is a process that has no relationship
to the screening of [a] large library of known compounds as called for in claim 1.”
Appeal Brief, page 7.
This argument is not persuasive. Claim 1 is not limited to a process of
screening a large library or database of known compounds. As discussed above,
the claim language is broad enough to encompass the hybridization assay
method disclosed by Evans. Since claim 1 reads on the method disclosed by
Evans, and Evans is prior art, claim 1 is anticipated.
Appellants also argue that they submitted a declaration under 37 CFR
§ 1.132 , which provided evidence that “the invention in the present case is not
disclosed in Evans.” Appeal Brief, page 6. The examiner, however, stated that
the declaration was not considered because it was not timely submitted.
Examiner’s Answer, page 8. Appellants “respectfully traversed” the examiner’s
position, on the basis that the declaration had been entered during prosecution of
the application that was the parent of the present application, and therefore
should have been considered in this application as well. See the Reply Brief,
page 4.
We decline to consider Appellants’ arguments based on the Brussolo
declaration, however, because the declaration was submitted after the final
rejection and the examiner refused to enter it. See the Examiner’s Answer, page
8. Appellants did not petition to have the examiner’s decision reversed, and this
board has no authority to review such decisions. See Manual of Patent
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Examining Procedure (MPEP) § 1002.02(c) (petitions relating to formal
sufficiency and propriety of declarations under 37 CFR § 1.132 are decided by
Technology Center Directors); § 1201 (“The line of demarcation between
appealable matters for the Board of Patent Appeals and Interferences and
petitionable matters for the Commissioner of Patents and Trademarks should be
carefully observed.”). Therefore, the Brussolo declaration is not properly a part
of the record on appeal and we have not considered it.
3. Obviousness
The examiner rejected claims 8, 10, 13-33, 36, and 37 as obvious in view
of Evans and Pomponi. The examiner relied on Evans for the disclosures
discussed above. The examiner cited Pomponi as teaching “an assay for CETP
[cholesteryl ester transfer protein] in multiple 96-well microtiter plates to test for
inhibition of various compounds where the compounds were placed in the wells
with appropriate dilution, a testing screen was performed and the inhibition was
determined.” Examiner’s Answer, page 6. The examiner concluded that
[i]t would have been obvious to one or ordinary skill in the art at the
time the invention was made to screen compounds of any type in
the method of Evans because Pomponi teaches different
compounds than Evans determined in arrays and one would have a
high expectation of success in employing known reaction formats to
perform known reactions.

Id.
“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.” In re Fritch, 972 F.2d 1260, 1265, 23 USPQ2d 1780, 1783 (Fed.
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Cir. 1992). “[I]dentification in the prior art of each individual part claimed is
insufficient to defeat patentability of the whole claimed invention. Rather, to
establish obviousness based on a combination of the elements disclosed in the
prior art, there must be some motivation, suggestion or teaching of the
desirability of making the specific combination that was made by the applicant.”
In re Kotzab, 217 F.3d 1365, 1369-70, 55 USPQ2d 1313, 1316 (Fed. Cir. 2000).
An adequate showing of motivation to combine requires “evidence that ‘a
skilled artisan, confronted with the same problems as the inventor and with no
knowledge of the claimed invention, would select the elements from the cited
prior art references for combination in the manner claimed.’” Ecolochem, Inc. v.
Southern Calif. Edison Co., 227 F.3d 1361, 1375, 56 USPQ2d 1065, 1075 (Fed.
Cir. 2000). “Combining prior art references without evidence of such a
suggestion, teaching, or motivation simply takes the inventor’s disclosure as a
blueprint for piecing together the prior art to defeat patentability—the essence of
hindsight.” In re Dembiczak, 175 F.3d 994, 999, 50 USPQ2d 1614, 1617 (Fed.
Cir. 1999).
In this case, we agree with Appellants that the examiner has not shown
that those skilled in the art would have been motivated to combine the teachings
of the cited references. The assay disclosed by Evans involves hybridization of
mixed probes with immobilized cosmid DNA to determine which cosmids share
overlapping sequences. See page 5030 (abstract). The assay disclosed by
Pomponi involved inhibition of the transfer of labeled cholesteryl ester from high
density lipoproteins to low density lipoproteins to identify compounds of potential
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use in treating atherosclerosis. See column 8, lines 35-50 and column 3, lines
43-52.
Other than the use of 96-well microtiter plates, the assays appear to have
nothing in common. The examiner has provided no evidence or scientific
reasoning to show “that ‘a skilled artisan, confronted with the same problems as
the inventor and with no knowledge of the claimed invention, would select the
elements from the cited prior art references for combination in the manner
claimed.’” Ecolochem, 227 F.3d at 1375, 56 USPQ2d at 1075.
Since the examiner has not shown that the cited references would have
suggested the instant claims to a person of ordinary skill in the art, the rejection
under 35 U.S.C. § 103 is reversed.
Other Issues
The examiner rejected claims 14-17, 32, and 33 only for obviousness over
Evans and Pomponi. For the reasons discussed above, the examiner’s rejection
must be reversed. We note, however, that claims 14-17 are directed to the
assay of claim 1, wherein the activity being assayed for is the presence or
absence of a gene associated with a malady or with a biological response. In
addition, claims 32 and 33 are directed to the assay of claim 1, where the
number of compounds in each test zone is 5-20 or 8-12, respectively.
We have concluded, supra, that Evans discloses an assay meeting the
limitations of claim 1. Since claims 14-17 are directed to assays to determine the
presence or absence of specific DNAs, and since claims 32 and 33 add only the
requirement of a specified number of compounds (e.g., probes), it may well be
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Application No. 09/163,572

that the teachings of Evans alone would have suggested these claims to a
person of ordinary skill in the art. Upon return of this case, the examiner should
review the claims individually and consider whether they would have been
obvious to a person of ordinary skill in the art based on the prior art, including
Evans.
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Application No. 09/163,572

Summary
The meaning of the claims is sufficiently clear when they are read in light
of the specification. We therefore reverse the rejection for indefiniteness. The
method defined by claim 1 reads on the assay method disclosed by Evans, and
we therefore affirm the rejection of claim 1 for anticipation. Claims 2-4 and 9 fall
with claim 1. However, we reverse the rejection for obviousness, because the
prior art would not have led those skilled in the art to combine the teachings of
the cited references. Therefore, claims 8, 10, 13-33, 36, and 37 are not subject
to any outstanding rejections.
No time period for taking any subsequent action in connection with this
appeal may be extended under 37 CFR § 1.136(a).
AFFIRMED IN PART

DONALD E. ADAMS )
Administrative Patent Judge )
)
)
) BOARD OF PATENT
ERIC GRIMES )
Administrative Patent Judge ) APPEALS AND
)
) INTERFERENCES
)
LORA M. GREEN )
Administrative Patent Judge )
Appeal No. 2001-0692 Page 15
Application No. 09/163,572

WILLIAM J. SCHRAMM
REISING, ETHINGTON, LEARMAN & McCULLOCH
P.O. BOX 4390
TROY, MI 48099

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