Ex Parte Wang et al

Patent Trial and Appeal Board

Jun 20, 2016

12464367 (P.T.A.B. Jun. 20, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
12/464,367 05/12/2009 YAN CHANG WANG
7590 06/21/2016
FLORIDA STATE UNIVERSITY RESEARCH FOUNDATION
95 CHIEFTAN WAY
SUITE 312
TALLAHASSEE, FL 32306
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.
00746.05.0002 1453
EXAMINER
SWOPE, SHERIDAN
ART UNIT PAPER NUMBER
1652
MAILDATE DELIVERY MODE
06/21/2016 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
Exparte YANCHANG WANG and SHU-YI SI1
Appeal2013-006414
Application 12/464,367
Technology Center 1600
Before ERIC B. GRIMES, ULRIKE W. JENKS, and JOHN G. NEW,
Administrative Patent Judges.
JENKS, Administrative Patent Judge.
uECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims directed to a
method of identifying Aurora kinase inhibitors. The Examiner rejects the
claims as lacking enablement, lacking descriptive support and obvious. We
have jurisdiction under 35 U.S.C. § 6(b).
We reverse and enter a new ground of rejection pursuant to 37 C.F.R.
§ 41.50(b) for independent claim 2.
1 According to Appellants, the Real Party in Interest is Florida State
University Research Foundation. (App. Br. 1.)
Appeal2013-006414
Application 12/464,367
STATEMENT OF THE CASE
Claims 2-6, 9-17, 19, 20, 22, 34-38, 50-53, 57, and 58 on appeal,2
and can be found in the Claims Appendix of the Appeal Brief. Claim 2 is
representative of the claims on appeal, and reads as follows:
2. A method comprising the following steps:
(a) measuring a total amount of growth over a specific period of
time of a population of wild-type yeast cells in or on a first
medium containing a test compound and a total amount of
growth over the specific period of time of a population of
hypomorphic ipll mutant yeast cells in or on a second medium
containing the test compound;
(b) comparing the total amount of growth of the population of
hypomorphic ipll mutant yeast cells to the total amount of
growth of the population of wild-type yeast cells over the
specific period of time; and
( c) determining whether the test compound is a putative Aurora
kinase inhibitor based on the comparison of step (b ),
wherein the test compound is determined to be a putative
Aurora kinase inhibitor in step ( c) if the total amount of growth
of the population of hypomorphic ipll mutant yeast cells is
lower than the total amount of growth of the population of wild-
type yeast cells over the specific period of time,
wherein the population of hypomorphic ipll mutant yeast cells
comprises ipll-321 mutant yeast cells or ipll-2 mutant yeast
cells, and
2 Appellants note that claims 59-61 were added in the After-Final
Amendment submitted Oct. 18, 2012, and entered by the Examiner in the
Advisory Action mailed Nov. 8, 2012 (App. Br. 4). We note that the claims
59-61 are not specifically addressed in the Advisory Action, but the
Examiner stated that entry of an after-final amendment is not a matter of
right and "Applicants' filing after final rejection requires further search and
consideration" (Adv. Action 2). The record therefore shows that the
Examiner did not enter claims 59-61.
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Application 12/464,367
wherein the first medium and the second medium have the
same composition exclusive of the test compound.
The other independent claims, claims 51 and 58, similarly recite the
limitation "wherein the ... populations of the hypomorphic ipll mutant
yeast cells comprise ipll-321 mutant yeast cells or ipll-2 mutant yeast
cells."
The following grounds of rejection are before us for review:
I. claims 2-6, 9-17, 19, 20, 22, 34-38, 50-53, 57, and 58 under
35 U.S.C. § 112, first paragraph as failing to provide an enabling
disclosure for identifying an Aurora inhibitor;
II. claims 2-6, 9-17, 19, 20, 22, 34-38, 50-53, 57, and 58 under
35 U.S.C. § 112, first paragraph as failing to provide a representative
number of yeast mutant species encompassed by the claims;
III. claims 2-6, 9-17, 34, 35, 50-53, 57, and 58 under 35 U.S.C.
§ 103(a) as unpatentable over Buvelot3 in view of Ditchfield;4
IV. claims 12, 14, 19, 20, and 22 under 35 U.S.C. § 103(a) as
unpatentable over Buvelot and Ditchfield in view of Pan; 5 and
V. claims 36-38 under 35 U.S.C. § 103(a) as unpatentable over
Buvelot and Ditchfield in view of Yang. 6
3 Stephanie Buvelot et al., The budding yeast Ipll/Aurora protein kinase
regulates mitotic spindle disassembly, 160 J. CELL BIO. 329-339 (2003).
4 Claire Ditchfield et al., Aurora B couples chromosome alignment with
anaphase by targeting BubRl, Mad2, and Cenp-E to kinetochores, 161 J.
CELL BIO. 267-280 (2003).
5 Witao Pan et al., Pyrimido-oxazepine as a versatile template for the
development of inhibitors of specific kinases, 15 BIOORGANIC &
MEDICINAL CHEMISTRY LETTERS 5474-5477 (2005).
6 Hao Yang et al., High level expression of His-tagged colicin 5 in E. coli
and characterization of its narrow-spectrum bactericidal activity and pore-
3
Appeal2013-006414
Application 12/464,367
1. Issue: Enablement
The Examiner takes the position that "the specification, while
being enabling for identifying an Aurora inhibitor by comparing the
effect of a test compound on growth of ipll and hypomorphic ipll-321
cells, does not reasonably provide enablement for identifying an Aurora
inhibitor by comparing the effect of a test compound on growth of a
composition comprising any combination of yeast strains expressing any
protein having any activity of any Aurora B kinase." (Ans. 4.)
Appellants contend that the Examiner "has failed to identify even a
single step ... that is not enabled by the specification ... [and thereby
has] failed to provide a reasonable explanation why the scope of
protection provided by any of the claims is not adequately enabled by the
specification." (App. Br. 5.)
The issue is: Does the Specification as filed provide an enabling
disclosure for a screening method using "hypomorphic ipll mutant yeast
cells compris[ing] ipll-321 mutant yeast cells or ipll-2 mutant yeast
cells" as claimed?
Findings of Fact
FF 1. Fig. 2B of the Specification, reproduced below shows the effect of
Jadomycin Ban aurora B inhibitor on the growth of ipll-321 yeast
cells.
forming action, 54 PROTEIN EXPRESSION AND PURIFICATION 309-317 (2007).
4
Appeal2013-006414
Application 12/464,367
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FIG. 2B shows "the relative percentages of growth measured as OD6oo for
wild-type and ipll-321 yeast cells treated with 10 µg/ml Jadomycin B
and other compounds at 25°C for 24 hours, versus untreated cells with
the results presented as means and standard deviations from three
separate experiments (p<0.05)" (Spec. iJ 17; see iii! 119, 129, and 130.)
FF2. The Specification provides:
hypomorphic mutation or allele of ~vll used in embodiments of
present screening methods may include ipll-321 described
herein and ... may [also] include ipll-2 .... [I]t is to be
understood that any known or later generated hypomorphic
mutation or allele of ipll may potentially be used according to
embodiments of present screening methods.
(Spec. ii 69.)
Principle of Law
"When rejecting a claim under the enablement requirement of section
112, the PTO bears an initial burden of setting forth a reasonable explanation
as to why it believes that the scope of protection provided by that claim is
not adequately enabled by the description of the invention provided in the
specification of the application; this includes, of course, providing sufficient
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Application 12/464,367
reasons for doubting any assertions in the specification as to the scope of
enablement." In re Wright, 999 F.2d 1557, 1561-62 (Fed. Cir. 1993).
Analysis
Based on the arguments presented by Appellants, and the Examiner
findings and conclusion, we find that Appellants have the better position.
Here, the Examiner's enablement rejection is predicated on the position that
"[t]he scope of each of these claims is not commensurate with the
enablement provided by the disclosure with regard to the extremely large
number of methods broadly encompassed by the claim. . . . [A] detailed
knowledge of the ways in which the protein's structure relates to its function
is needed" (Ans. 5). As we understand the Examiner's rejection, the
Examiner appears to interpret the claimed method as encompassing any ipll
mutation presently known as well as later discovered. Indeed, the
Specification tells us that "hypomorphic mutation or allele of ipll" could
encompass "any known or later generated hypomorphic mutation or allele of
ipll" (FF2). The claims, however, are not so broad. Specifically, claim 2
recites "wherein the population of hypomorphic ipll mutant yeast cells
comprises ipll-321 mutant yeast cells or ipll-2 mutant yeast cells." We note
that the other independent claims, claims 51 and 58, similarly recite this
limitation.
The Specification exemplifies a yeast assay comparing wild type and
ipll-321 mutant yeast cells under conditions using a variety of inhibitors as
well as different concentration of the Jadomycin B inhibitor (FFl). Thus,
the Specification has exemplified the use of a hypomorphic ipll-321 mutant
to assay for the effect of the inhibitor; the assay shows that when the
inhibitor is directed to Aurora kinase then the ipll-321 mutant growth is
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Application 12/464,367
restricted when compared to wild type and this growth is also shown to have
dose response effect (FFl). Both the ipll-321 mutant and wild type express
Aurora kinase activity, although the ipll-321 mutant contains a much lower
level of this enzyme as evidenced by the dose response effect comparing the
response of the wild type and mutant to the Jadomycin B inhibitor (FFl).
Because the claimed assay is limited by the "wherein" clause to the use of
hypomorphic ipll-321 or ipll-2 mutants we are not persuaded that the
Examiner has met the burden of setting forth a reasonable explanation as to
why the scope of protection provided by the claims is not adequately
enabled by the Specification. Accordingly, we reverse the Examiner's
enablement rejection.
II. Issue: Written Description
The Examiner's position is that the methods disclosed in the claims
represent a genus of methods, however, the "specification teaches only one
representative species of such methods. . . . [T]he specification fails to
describe any other representative species by any identifying characteristics
or properties other than the functionality of being a method for identifying
Aurora inhibitors" (Ans. 8).
We agree with Appellants' position (App. Br. 6-7) that the Examiner
has not adequately articulated a sufficient rationale to explain how the
claims are directed to a genus of methods. Claim 2 recites the limitation
"wherein the population of hypomorphic ipll mutant yeast cells comprises
ipll-321 mutant yeast cells or ipll-2 mutant yeast cells." Accordingly, claim
2 is limited to the use of either ipll-321 or ipll-2 mutant yeast cells in the
assay. Contrary to the Examiner's position, the claims are not directed to a
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Appeal2013-006414
Application 12/464,367
genus of methods but instead are limited to methods that utilize either ipll -
32 l or ipll-2 mutant yeast cells. We note that the other two independent
claims, claims 51 and 58, similarly recite the limitation "wherein the ...
populations of the hypomorphic ipll mutant yeast cells comprise ipll-321
mutant yeast cells or ipll-2 mutant yeast cells."
"[T]he written description requirement does not demand either
examples or an actual reduction to practice; a constructive reduction to
practice that in a definite way identifies the claimed invention can satisfy the
written description requirement." Ariad Pharms., Inc. v. Eli Lilly & Co., 598
F.3d 1336, 1352 (Fed. Cir. 2010) (en bane). Here, the Specification
discloses assays that utilize ipll-3 21 mutant yeast cells; this exemplifies a
description of one of the two mutants claimed (FFl and FF2) and provides
an actual reduction to practice for that mutant. Additionally, the
Specification discloses that the other mutant was known in the art at the time
of filing (FF2). Based on the evidence before us we cannot support the
Examiner's position that the Specification lacks written descriptive support
for the methods set out in the independent claims. Accordingly, we reverse
the Examiner's written description rejection.
111.-V. Issue: Obviousness over Buvelot and Ditc/1field
The Examiner has rejected all of the claims as obvious based on the
combination of Buvelot and Ditchfield (claims 2-6, 9-17, 34, 35, 50-53, 57,
and 58), or the combination of Buvelot and Ditchfield in conjunction with
either Pan (claims 12, 14, 19, 20, and 22) or Yang (claims 36-38). Because
all of these rejections rely upon the teaching of Buvelot and Ditchfield
regarding the yeast screening method as claimed, the same issue is
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Application 12/464,367
dispositive for all of these rejections, so we will consider the rejections
together.
The Examiner finds that Buvelot teaches "hypomorphic mutant yeast
strain ipll-321" and Ditchfield "teaches screening compounds for an effect
on Aurora B inhibition in vitro" (Ans. 9). The Examiner acknowledges that
Buvelot "does not teach screening for inhibitors of Aurora kinase B by
comparing the effect of test agents on growth of the parent ipl 1 strain
compared to growth of the Aurora B hypomorphic ipll-321 strain" (Ans. 9).
According to the Examiner "[t]he use of hypomorphic yeast for screening
was well known in the art" (Ans. 9; see also 16 ("It is noted that Appellants
have not requested evidence from the Office supporting the assertion that
methods of using hypomorphic yeast, as a way to screen for compounds that
affect the function of the protein whose activity has been reduced
genetically, was well known in the art").) In the Answer the Examiner cites
to Bharucha7 and Kotwaliwale8 to evidence that the use of hypomorphic
yeast is well known (Ans. 19).
Appellants contend that the combination of Buvelot and Ditchfield
"taken either alone or in combination, do not teach or suggest the claimed
feature of'( c) determining whether the test compound is a putative Aurora
kinase inhibitor based on [a comparison the total amount of growth of the
population of hypomorphic ipl 1 mutant yeast cells to the total amount of
7 Nike Bharucha et al., Yeast Genomics and Drug Target Identification,
10 COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING, 618-634
(2007).
8 Chitra V. Kotwaliwale et al., A Pathway Containing the Ipll/Aurora
Protein Kinase and the Spindle Midzone Protein Asel Regulates Yeast
Spindle Assembly, 13 DEVELOP. CELL 433--445 (2007).
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Appeal2013-006414
Application 12/464,367
growth of the population of wild-type yeast cells over a specific period of
time]."' (App. Br. 8.)
The issue is: Does the preponderance of the evidence of record
support the Examiner's position that the combination of Buvelot and
Ditchfield renders the claimed method obvious?
Findings of Fact
FF3. Buvelot teaches that "[t]he Ipll/Aurora protein kinases are key
regulators of chromosome segregation and cytokinesis." (Buvelot
329.) "In budding yeast, there is a single essential Aurora protein
kinase, Ipll. . . . In ipll mutant cells, sister chromatids are pulled to
the same spindle pole instead of opposite poles." (Buvelot 330.)
FF4. Buvelot teaches "imaging of wild-type and ipll-321 mutants
containing Tubl-GFP." (Buvelot 331.)
FF5. Ditchfield teaches ZM447439, an inhibitor of Aurora A and Aurora B.
"In in vitro kinase assays using purified recombinant proteins,
ZM447439 inhibited Aurora A and B with ICso values of 110 and 130
nM, respectively .... Based on data from model systems, we
predicted that an Aurora inhibitor should prevent cell division and
inhibit phosphorylation of histone H3 on serine 10." (Ditchfield 268;
Ans. 9.)
Principle of Law
"An examiner bears the initial burden of presenting a prima facie case
of obviousness." In re Huai-Hung Kao, 639 F.3d 1057, 1066 (Fed. Cir.
2011. In satisfying this initial burden, "[i]t is impermissible to use the
claimed invention as an instruction manual or 'template' to piece together
the teachings of the prior art so that the claimed invention is rendered
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Application 12/464,367
obvious." Jn re Fritch, 972 F.2d 1260, 1266 (Fed. Cir. 1992). Stated
differently, to establish obviousness, there must be "an apparent reason to
combine the known elements in the fashion" recited in the claims. KSR Int 'l
Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007).
Analysis
Appellants contend that the combination of Buvelot and Ditchfield
taken alone or in combination does not present a prima facie showing of
obviousness (App. Br. 8)9 because the references fail to teach or suggest "the
claimed feature of ' ( c) determining whether the test compound is a putative
Aurora kinase inhibitor based on [a comparison the total amount of growth
of the population of hypomorphic ipl 1 mutant yeast cells to the total amount
of growth of the population of wild-type yeast cells over a specific period of
time]."' (Id.)
The Examiner takes the position that it was up to Appellants to
challenge the Examiner with respect to the finding that "[t]he use of
hypomorphic yeast for screening was well known in the art" (see Ans. 16
("It is noted that Appellants have not requested evidence from the Office
supporting the assertion that methods of using hypomorphic yeast ... w[ ere]
well known in the art").)
We find that Appellants have the better position. As an initial matter,
we note that Appellants repeatedly pointed out during prosecution that
9 Appellants contend that the Examiner's Answer presents a new ground of
rejection because the Examiner relies on additional references to support the
obviousness rejection (Reply Br. 2-3). Whether an Answer includes a new
ground of rejection, however, is an issue that can be reviewed only by way
of petition. MPEP § 1207.03(IV). Appellants did not petition to have the
rejection in the Answer designated a new ground of rejection.
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Application 12/464,367
Buvelot and Ditchfield alone or in combination do not teach the determining
step ( c) as set out in the claim (App. Br. 8; see Response to Office Action
18, submitted June 6, 2012). The Examiner does not dispute that neither
Buvelot nor Ditchfield discloses or suggests "screening for inhibitors of
Aurora kinase B by comparing the effect of test agents on growth of the
parent ipll strain compared to growth of the Aurora B hypomorphic ipll-321
strain" (Ans. 9). The Examiner's position throughout the prosecution,
however, is that "[t]he use of hypomorphic yeast for screening was well
known in the art" (Ans. 9). We consider whether the Examiner properly
relies on "official notice" with respect to the claimed method elements.
It is never appropriate to rely solely on "common knowledge"
in the art without evidentiary support in the record, as the
principal evidence upon which a rejection was based. [In re]
Zurko, 258 F .3d [1379,] ... 1385 [(Fed. Cir. 1993)] ...
("[T]he Board cannot simply reach conclusions based on its
own understanding or experience-or on its assessment of what
would be basic knowledge or common sense. Rather, the
Board must point to some concrete evidence in the record in
support of these findings."). While the court explained that, "as
an administrative tribunal the Board clearly has expertise in the
subject matter over which it exercises jurisdiction," it made
clear that such "expertise may provide sufficient support for
conclusions [only] as to peripheral issues." Id. at 1385-86 ....
As the court held in Zurko, an assessment of basic knowledge
and common sense that is not based on any evidence in the
record lacks substantial evidence support. Id. at 1385.
MPEP 2144.03
Here, the Examiner points to Buvelot as disclosing wild-type and ipll-
321 mutants (Ans. 9, see FF3 and FF4) and Ditchfield as teaching "Aurora B
inhibition in vitro" (Ans. 9; see FF5). The Examiner acknowledges that
Buvelot "does not teach screening for inhibitors of Aurora kinase B by
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Application 12/464,367
comparing the effect of test agents on growth of the parent ipl 1 strain
compared to growth of the Aurora B hypomorphic ipll-321 strain" (Ans. 9).
Although Ditchfield discloses screening inhibitors for their effect on Aurora
B, the reference uses purified proteins for these assays and, therefore, does
not compare yeast growth patterns (FF5). Thus, the Examiner relies on
common knowledge to establish all method steps as presently claimed. In
other words the Examiner relies on common knowledge as the principal
evidence in the rejection which is inappropriate. See In re Zurko 258 F.3d
1379, 1385 (Fed. Cir. 1993) ("With respect to core factual findings in a
determination of patentability . . . the Board must point to some concrete
evidence in the record in support of these findings.[] To hold otherwise
would render the process of appellate review for substantial evidence on the
record a meaningless exercise.")
On balance we find that Appellants adequately traversed the
Examiner's reliance on common knowledge by arguing that the comparison
step is not suggested by the combination of references (App. Br. 9; see
Reply filed June 6, 2012, 17). We do not agree with the Examiner's
assessment "that Appellants have not [previously] requested evidence from
the Office supporting the assertion that methods of using hypomorphic yeast,
as a way to screen for compounds that affect the function of the protein
whose activity has been reduced genetically, was well known in the art"
(Ans. 16).
In the Answer the Examiner cites Bharucha10 to establish that the use
of hypomorphic yeast was known and obvious. (Ans. 19; see Ans. 9 ("[t]he
10 Nike Bharucha et al., Yeast Genomics and Drug Target Identification,
10 COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING, 618-634
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Application 12/464,367
use of hypomorphic yeast for screening was well known in the art").) We
think it appropriate to remind the Examiner that references relied on to
support a rejection under 35 U.S.C. § 103 should be included in the
statement of rejection. As stated in In re Hoch, 428 F.2d 1341, 1342 n.3
(CCPA 1970) ("Where a reference is relied on to support a rejection,
whether or not in a 'minor capacity,' there would appear to be no excuse for
not positively including the reference in the statement of the rejection.").
See also MPEP 706.02U). Where, as here, the Examiner lists two references
"relied upon in the rejection of claims under appeal" and includes those
references, and only those references, in the statement of rejection under
35 U.S.C. § 103, we have limited our review of the prima facie case of
obviousness to those references.
We conclude that the preponderance of the evidence of record does
not support the Examiner's conclusion that the combination of Buvelot and
Ditchfield alone teaches the claimed method of screening for Aurora B
inhibitors We therefore reverse the rejections under 35 U.S.C. § 103(a) that
rely on the combination of Buvelot and Ditchfield.
New Ground of Rejection for Independent Claim 2
We enter a new ground of rejection for claim 2 under 35 U.S.C.
§ 103(a) as unpatentable over the combination of Buvelot, Ditchfield, and
Bharucha.
(2007).
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Application 12/464,367
Findings of Fact
FF6. Fig. 1 of Bharucha, reproduced below, teaches the use of transposon
nmtagenesis leading to the creating of nmtagenized alleles by
replacing genomic copies.
"'~''''~~'"" i~~~l~m'.El@H•~~~~;:il
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Homologous recombination leads to the integration of the
mutagenized allele at its corresponding genomic locus,
replacing its genomic copy. Transformants displaying B-
galactosidase activity contain transposon insertions within gene
coding sequences; these transformants are further screened for
altered sensitivity to various inhibitors by growing the mutants
15
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Application 12/464,367
on plates containing sub-lethal concentrations of the particular
inhibitors and monitoring growth. A wild-type strain and
mutants grown on a plate lacking the drug are used for
comparison. Absence of growth indicates sensitivity to the
particular drug.
(Bharucha 620, Fig. l; Ans. 19.)
FF7. Bharucha teaches:
The yeast haploid gene deletion collection ... was used ... to
identify the cellular processes and pathways. . . . The principle
was that loss of a gene in a pathway affected by a drug could
lead to a synthetic lethal effect, where the combination of a
deletion and a normally sublethal drug-dose results in cell
death.
(Bharucha 621.)
FF8. Bharucha teaches that "[t]he use of multiple chemicals in this study
allowed researchers to distinguish strains with specific sensitivity to a
single class of compounds from those sensitive to more than one
unrelated compound. By performing the screens in liquid cultures,
processes more subtly affected by a chemical were also uncovered."
(Bharucha 622.)
FF9. Bharucha teaches:
[Using] the yeast deletion collection to explore the genetic
interaction between TOR (Target of Rapamycin) and other
yeast genes. . . . In this study, growth of 2,216 nonessential
gene deletion strains and fifty heterozygous essential diploid
deletion strains on plates containing rapamycin were compared
against wild type growth under the same conditions to
determine drug sensitivity.
(Bharucha 622.)
FFlO.Bharucha teaches using haploinsufficiency to study drug effects in
yeast. "The principle behind this 'drug-induced haploinsufficency' is
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Application 12/464,367
that lowering the dosage of a single gene in diploid yeast could result
in a heterozygote that is sensitized to any drug that acts on the product
of this gene." (Bharucha 622.) These heterozygous yeast strains were
grown with sublethal doses of drugs. "The growth rate was compared
to that of a wild type strain under the same conditions. The results
indicated that each mutant displayed sensitivity in the presence of the
drug that targeted its deleted gene product." (Bharucha 622.)
Bharucha explains that this type of screening is useful "not only in
validating previously known targets but also in identifying potential
new targets for many of the compounds tested." (Bharucha 622.)
FFl l.Bharucha teaches that "another advantage of these drug-screening
approaches, no prior knowledge of the mode of action of the drug is
required, allowing novel drug activities to be uncovered in a
systematic and unbiased fashion." (Bharucha 623.)
Principle of Law
"The combination of familiar elements according to known methods
is likely to be obvious when it does no more than yield predictable results."
KSR Int'! Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007). "If the claim
extends to what is obvious, it is invalid under§ 103." KSR Int'! Co. v.
Teleflex Inc., 550 U.S. 398, 419 (2007).
Analysis
Bharucha teaches the use of transposons to create homologous
recombination in yeast by inserting mutations or creating deletions in the
yeast genes (FF7). The transformed yeast and wild type yeast can be studied
side-by-side to test the effects of inhibitors (see FF6-FF11 ). Bharucha
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Application 12/464,367
explains that the yeast with haploid gene deletions can be used to study
drugs that affect particular pathways. Here, a sublethal dosage of a drug for
a wild type yeast causes cell death in yeast with the haploid gene deletion
(FF7). Bharucha also discloses comparing the growth rate of yeast carrying
heterozygote genes with the growth rate of wild type strains. Growth
sensitivity in the presence of the drug indicates that the drug affects the
deleted gene product (FFlO). Bharucha indicates that the use of these
screening methods can identify new drug targets, test and validate known
targets, as well as allowing for the testing of compounds that have unknown
drug action (FF 10 and FF 11 ). Buvelot teaches that Ipll I Aurora protein
kinases are key regulators for chromosome segregations (FF3). Buvelot
teaches the use of wild type and Ipll-321 mutants in studying the role of Ipll
in spindle disassembly using time lapse microscopy (Buvelot Abstract; FF4).
Ditchfield describes using in vitro kinase assays to screen ZM447439 for the
effect on Aurora A and B (FF5).
Applying the KSR standard of obviousness to the findings of fact, we
conclude that it would have been obvious to an ordinary artisan of ordinary
creativity to use the yeast screening methods disclosed by Bharucha in order
to determine and validate the effect of a known Aurora kinase inhibitor on a
known yeast strain that has a decreased level of Ipll I Aurora protein kinases
(FF3, FF4, FFlO). We agree with the Examiner's explanation "that
determining growth in the presence and absence of a test compound is
standard protocol [as evidenced by the teachings of Bharucha.] ...
Motivation to do so is provide by the desire to identify agents that affect
Aurora B-mediated growth and the advantage of using the ipll-32! strain
having lower Aurora B activity" (Ans. 9; see FF3-FF11). We agree with the
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Appeal2013-006414
Application 12/464,367
Examiner that when you apply a known technique (FF6-FF11) to a known
yeast mutant (FF3 and FF 4) in order to validate the effect of a known drug
(FF5) there is a high expectation of success (see Ans 10 ("The expectation of
success is high, as all reagents and steps were known in the art"). Such a
combination is merely a "predictable use of prior art elements according to
their established functions." KSR, 550 U.S. at 417.
Because the Board's function is primarily one of review, we leave it
to the Examiner to consider the patentability of claims 3-6, 9-17, 19, 20, 22,
34-38, 50-53, 57, and 58 in view of our findings in the new ground of
rejection herein. No inference should be drawn on the patentability of
dependent claims 3-6, 9-17, 19, 20, 22, 34-38, 50-53, 57, and 58 from our
decision not to enter new grounds of rejection for these claims.
SUMMARY
We reverse the rejection of claims 2-6, 9-17, 19, 20, 22, 34-38, 50-
53, 57, and 58 under 35 U.S.C. § 112, first paragraph as failing to provide
enablement for identifying an Aurora inhibitor by comparing the effect of a
test compound on growth of a composition comprising any combination of
yeast strains.
We reverse the rejection of claims 2-6, 9-17, 19, 20, 22, 34-38, 50-
53, 57, and 58 under 35 U.S.C. § 112, first paragraph as failing to provide a
representative number of species encompassed by the claims.
We reverse the rejection of claims 2-6, 9-17, 34, 35, 50-53, 57, and
58 under 35 U.S.C. § 103(a) over Buvelot in view of Ditchfield.
We reverse the rejection of claims 12, 14, 19, 20, and 22 under
35 U.S.C. § 103(a) as unpatentable over Buvelot and Ditchfield in view of
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Appeal2013-006414
Application 12/464,367
Pan.
We reverse the rejection of claims 36-38 under 35 U.S.C. § 103(a)
35 U.S.C. § 103(a) as unpatentable over Buvelot and Ditchfield in view of
Yang.
We enter a new ground of rejection for claim 2 under 35 U.S.C.
§ 103(a) as obvious over Buvelot, Ditchfield, and Bharucha. We leave it to
the Examiner to determine the patentability of the remaining pending claims
3-6, 9-17, 19, 20, 22, 34-38, 50-53, and 57- 61 in view of the new ground
of rejection for independent claim 2 based on the prior art.
TIME PERIOD FOR RESPONSE
This decision contains new ground of rejection pursuant to 37 C.F.R.
§ 41.50(b) (Sept. 13, 2004; revised, 76 FR 72270, Nov. 22, 2011, effective
Jan. 23, 2012). 37 C.F.R. § 41.50(b) provides "[a] new ground of rejection
pursuant to this paragraph shall not be considered final for judicial review."
37 C.F.R. § 41.50(b) also provides that Appellants, WITHIN TWO
MONTHS FROM THE DATE OF THE DECISION, must exercise one of
the following two options with respect to the new grounds of rejection to
avoid termination of the appeal as to the rejected claims:
(1) Reopen prosecution. Submit an appropriate amendment of the
claims so rejected or new evidence relating to the claims so rejected,
or both, and have the matter reconsidered by the Examiner, in which
event the proceeding will be remanded to the Examiner. ...
(2) Request rehearing. Request that the proceeding be reheard under
§ 41.52 by the Board upon the same record ....
REVERSED; 37 C.F.R. § 41.50(b)
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