Ex Parte Buxton

Board of Patent Appeals and Interferences

Aug 25, 2009

10331375 (B.P.A.I. Aug. 25, 2009)

UNITED STATES PATENT AND TRADEMARK OFFICE
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
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
10/331,375 12/30/2002 Iain Buxton D6426 2757
7590 08/26/2009
David L. Parker
FULBRIGHT & JAWORSKI L.L.P.
600 Congress Avenue, Suite 2400
Austin, TX 78701
EXAMINER
FETTEROLF, BRANDON J
ART UNIT PAPER NUMBER
1642
MAIL DATE DELIVERY MODE
08/26/2009 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 BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte IAIN BUXTON
__________

Appeal1 2009-002838
Application 10/331,375
Technology Center 1600
__________

Decided: August 26, 2009
__________

Before LORA M. GREEN, FRANCISCO C. PRATS, and
STEPHEN WALSH Administrative Patent Judges.

GREEN, 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 2-8 and 10-25.

1 The Oral Hearing scheduled for August 4, 2009, was waived.
Appeal 2009-002838
Application 10/331,375

2
We have jurisdiction under 35 U.S.C. § 6(b).

STATEMENT OF THE CASE
The claims are directed to a method of inhibiting tumor angiogenesis
using an inhibitor of the activity of nucleoside diphosphate kinase-B.
Claims 2, 4, and 10 are representative of the claims on appeal, and read as
follows:
2. A method of inhibiting tumor cell angiogenesis in a human tumor
expressing and secreting nucleoside diphosphate kinase-B, comprising the
steps of: a) identifying a human patient having a tumor, the cells of which
express and secrete nucleoside diphosphate kinase-B; and b) contacting said
cells of such a tumor with an inhibitor of the activity of nucleoside
diphosphate kinase-B.

4. The method of claim 2, wherein the inhibitor of nucleoside
diphosphate kinase-B comprises ellagic acid, epigallocatechin gallate, or
epicatechin gallate.

10. The method of claim 4, wherein the inhibitor of nucleoside
diphosphate kinase-B comprises ellagic acid.

The Examiner relies on the following evidence:
Morre WO 00/57875 Oct. 5, 2000
Castonguay et al. Antitumorigenic and antipromoting activities of ellagic
acid, ellagitannins and oligomeric anthocyanin and procyanidin, 10 Int. J.
Oncol., 367-373 (1997).

Appellant relies on the following evidence:
Konishi N et al., Expression of nm23-H1 and nm23-H2 proteins in prostate
carcinoma, 84 Jpn J Cancer Res. 10, 1050-1054 (1993) (Abstract only).

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Martinez JA et al. Overexpression of nm23-H1 and nm23-H2 genes in
colorectal carcinomas and loss of nm23-H1 expression in advanced tumour
stages, 37 Gut. 5, 712-20 (1995) ((Abstract only).

Okabe-Kado J et al. Expression of cell surface NM23 proteins of human
leukemia cell lines of various cellular lineage and differentiation stages, 26
Leuk. Res. 6, 569-76 (2002) (Abstract only).

Mandai M et al. Expression of metastasis-related nm23-H 1 and nm23-H2
genes in ovarian carcinomas: correlation with clinicopathology, EGFR, c-
erbB-2, and c-erbB-3 genes and sex steroid receptor expression 1:54 Cancer
Res., 7, 1825-30 (1994) (Abstract only).

Chen HY et al. Prognostic value of nm23 expression in stage IB1 cervical
carcinoma, 31 Jpn J Clin. Oncol., 7, 327-32 (2001) (Abstract only).

Belev B et al. Nm23 gene product expression in invasive breast cancer--
imunohistochemical analysis and clinicopathological correlation, 41 Acta
Oncol. 4, 355-61 (2002) (Abstract only).

Sheikh Het al. NM-23 gene loss of heterozygosity and protein expression in
high-stage laryngeal squamous cell carcinomas, 15 Diagn Mol Pathol 1, 1-6
(2006) (Abstract only).

Steeg PS et al. NM23 and breast cancer metastasis. (Review), 25 Breast
Cancer Res Treat. 2, 175-87 (1993)
Sarris Met al. Cytoplasmic expression of nm23 predicts the potential for
cerebral metastasis in patients with primary cutaneous melanoma, 14
Melanoma Res. 1, 23-7 (2004) (Abstract only).

We affirm-in-part

ISSUE (Anticipation)
The Examiner finds that claims 2-8, 11, 12, 14, 15, 17, 18, 20-22, 24,
and 25 are anticipated by Morre.
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Appellant contends that that the claimed method differs from Morre’s
manipulative steps. Appellant contends further that Morre cannot anticipate
the claims because the reference does not expressly or inherently disclose a
tumor that expresses and secretes NDPK-B.
Thus, the issues on appeal are: 1) Do the manipulative steps claimed
differ from Moore’s steps? and 2) As Morre does not expressly disclose a
tumor that expresses and secretes NDPK-B, has Appellant demonstrated that
the Examiner erred in finding that Morre inherently discloses a tumor that
expresses and secretes NDPK-B, thus anticipating claim 1?

FINDINGS OF FACT
FF1 According to the Specification, “the present invention relates to
secretion of nucleoside diphosphate kinase (NDPK) from human tumors and
the effects of inhibiting nucleoside diphosphate kinase activities.” (Spec. 1-
2.)
FF2 The Specification teaches that “nucleoside diphosphate kinase-B [is]
secreted as a phosphoprotein into the extracellular environment by a variety
of human tumors (e.g. breast, lung, colon, and prostate cancer cells).” (Id. at
4-5.) The Specification teaches further that “aggressive human tumor cells
from disparate tissues were found to secrete nucleoside diphosphate kinase-
B (NDPK-B) into the extracellular environment.” (Id. at 13.)
FF3 The Specification teaches further that “a series of structurally related
non-nucleotide anticancer compounds such as ellagic acid (EA),
epigallocatechin gallate (EGCG), and epicatechin gallate (ECG) inhibit the
activity of secreted nucleoside diphosphate kinase-B as well as
angiognenis.” (Id. at 5.)
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FF4 The Examiner rejects claims 2-8, 11, 12, 14, 15, 17, 18, 20-22, 24, and
25 under 35 U.S.C. § 102(b) as being anticipated by Morre (Ans. 3). As
Appellant does not argue the claims separately, we focus our analysis on
claim 2, and claims 3-8, 11, 12, 14, 15, 17, 18, 20-22, 24, and 25 stand or
fall with that claim. 37 C.F.R. § 41.37(c)(1)(vii)
FF5 The Examiner finds that Morre teaches “a method of treating cancer
or solid tumor comprising administering a therapeutically effective amount
of a catechin to a human in need of such therapy,” wherein the cancers may
include colon, breast, prostate, and lung cancers (Ans. 3).
FF6 The Examiner further finds that “catechin’s include, but are not
limited to, epigallocatechin gallate and epicatechin gallate.” (Id.)
FF7 The Examiner finds that “[a]lthough the prior art does not teach
inhibition of nucleoside diphosphate kinase-B, the teachings of the prior art
administer the same composition for the purpose of treating cancer wherein
nucleoside diphosphate kinase-B would inherently be inhibited resulting in
inhibition of tumor cell angiogenesis.” (Id.)
FF8 The Examiner further finds that there is no difference in the
manipulative steps required by the claimed invention and that taught by
Moore (id.).
FF9 Morre relates to a method of treating cancer or solid tumors by
administering a therapeutically acceptable amount of catechins to a mammal
in need of such therapy (Morre, p. 7).
FF10 Morre teaches that the catechins may comprise epigallocatechin
gallate, epicatechin gallate, epigallocatechin, and epicatechin (id.).
FF11 Morre teaches:
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Cancers that can be treated by the methods of the present
invention include, but not limited to human sarcomas and
carcinomas, e.g., fibrosarcoma, myxosarcoma, liposarcoma,
chondrosarcoma, osteogenic sarcoma, chordoma,
angiosarcoma, endotheliosarcoma, lyrnphangiosarcoma,
lymphangioendotheliosarcoma, synovioma, mesothelioma,
Ewing’s tumor, leiomyosarcoma, rhabdomyosarcoma, colon
carcinoma, pancreatic cancer, breast cancer, ovarian cancer,
prostate cancer, squamous cell carcinoma, basal cell carcinoma,
adenocarcinoma, sweat gland carcinoma, sebaceous gland
carcinoma, papillary carcinoma, papillary adenocarcinomas,
cystadenocarcinoma, medullary carcinoma, bronchogenic
carcinoma, renal cell carcinoma, hepatoma, bile duct
carcinoma, choriocarcinoma, seminoma, embryonal carcinoma,
Wilms’ tumor, cervical cancer, testicular tumor, lung
carcinoma, small cell lung carcinoma, bladder carcinoma,
epithelial carcinoma, glioma, astrocytoma, medulloblastoma,
craniopharyngioma, ependymoma, pinealoma,
hemangioblastoma, acoustic neuroma, oligodendroglioma,
meningioma, melanoma, neuroblastoma, retinoblastoma;
leukemias, e.g., acute lymphocytic leukemia and acute
myelocytic leukemia (myeloblastic, promyelocytic,
myelomonocytic, monocytic and erythroleukemia); chronic
leukemia (chronic myelocytic (granulocytic) leukemia and
chronic lymphocytic leukemia); and polycythemia vera,
lymphoma (Hodgkin’s disease and non-Hodgkin’s disease),
multiple myeloma, Waldenström’s macroglobulinemia, and
heavy chain disease.

(Id. at 17-18.)
FF12 Appellant relies on numerous abstracts to demonstrate that not all
tumors express and secrete NDPK-B (App. Br. 7-9).
FF13 For example, Konishi teaches that “[o]f the 80 cases on nonmetastatic
prostate carcinoma examined, . . . 60% (48/80) were immunoreactive for . . .
nm23-H2 protein.” nm23-H2 is the gene encoding NDPK-B. (App. Br. 7.)

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PRINCIPLES OF LAW
Our mandate is to give claims their broadest reasonable interpretation.
In re American Academy of Science Tech Center, 367 F.3d 1359, 1364, (Fed.
Cir. 2004). “An essential purpose of patent examination is to fashion claims
that are precise, clear, correct, and unambiguous. Only in this way can
uncertainties of claim scope be removed, as much as possible, during the
administrative process.” In re Zletz, 893 F.2d 319, 322 (Fed. Cir. 1989).
“A single prior art reference that discloses, either expressly or
inherently, each limitation of a claim invalidates that claim by anticipation.”
Perricone v. Medicis Pharmaceutical Corp., 432 F.3d 1368, 1375 (Fed. Cir.
2005). In Cruciferous Sprout, the court stated “[i]t is well settled that a prior
art reference may anticipate when the claim limitations not expressly found
in that reference are nonetheless inherent in it.” In re Cruciferous Sprout
Litigation, 301 F.3d 1343, 1349 (Fed. Cir. 2002). In addition, inherent
anticipation does not require intent or recognition that a prior art process
achieve a result which is claimed. “Inherency is not necessarily coterminous
with the knowledge of those of ordinary skill in the art. Artisans of ordinary
skill may not recognize the inherent characteristics or functioning of the
prior art.” MEHL/Biophile Intern. Corp. v. Milgraum, 192 F.3d 1362, 1365
(Fed. Cir. 1999).

ANALYSIS
Appellant argues that the manipulative steps of Moore and claim 2 are
not the same, as claim 2 “require[s] first identifying a patient having a tumor
that ‘express and secrete’ NDPKB, yet nowhere does Morre teach such an
invention, either expressly or inherently.” (App. Br. 9.)
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Claim 2 recites the step of “identifying a patient having a tumor, the
cells of which express and secrete nucleoside diphoshate kinase-B.” Giving
the claim its broadest reasonable interpretation, the only manipulative step
required is identifying a patient having a tumor, which is taught by Morre.
Appellant has not directed us to a narrower definition of the treatment
method in the Specification, e.g., a method definition that requires
identifying the patient’s tumor by its secretory properties and disclaims the
broader method. The recitation “the cells of which express and secrete
nucleoside diphoshate kinase-B” is thus only an expression of an inherent
property of the tumor. As discussed below, the evidence shows that in a
certain percentage of Morre’s patients identified as having a tumor treatable
with catechins , the tumor cells expressed and secreted nucleoside
diphoshate kinase-B.
Appellant argues further that “Morre does not anticipate the claims
because it does not expressly or inherently disclose a tumor that expresses
and secretes NDPK-B.” (App. Br. 4.) Appellant cites MEHL/Biophile Int’l
Corp. v. Milgraum, 192 F.3d at 1365, for the proposition that inherency is
not established by probabilities or possibilities, and that occasional results
are not inherent (App. Br. 5). Thus, Appellant asserts, “the mere possibility
that one of the cancers set forth in Morre might contain cancer cells that
express and secrete NDPK-B is not sufficient to establish inherent
anticipation.” (Id. at 6.) Appellant relies on abstracts of relevant
publications that “demonstrate that not all tumors express and secrete
NDPK-B.” (Id. at 7; see id. at 8-9 for list of abstracts).)
Appellant’s arguments have been carefully considered, but are not
convincing. Appellant essentially appears to be arguing that as the art does
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not establish that every tumor expresses and secretes diphosphate kinase-B,
Morre cannot anticipate the claimed subject matter. That is not the standard,
however, by which anticipation is determined.
Inherent anticipation does not require intent or recognition that a prior
art process achieve a result which is claimed. “Inherency is not necessarily
coterminous with the knowledge of those of ordinary skill in the art.
Artisans of ordinary skill may not recognize the inherent characteristics or
functioning of the prior art.” MEHL/Biophile, 192 F.3d at 1365. Morre
teaches a method of treating cancer or solid tumors by administering an
inhibitor of the activity of nucleoside disphosphate kinase-B, such as
epigallocatechin gallate and epicatechin gallate. The record established by a
preponderance of the evidence that a percentage of cancers and solid tumors
are known to express and secrete nucleoside diphosphate kinase-B. See,
e.g., Ethicon, Inc. v. Quigg, 849 F.2d 1422, 1427 (Fed. Cir. 1988)
(explaining the general evidentiary standard for proceedings before the
Office); In re Kollar, 286 F.3d 1326, 1329 (Fed. Cir. 2002) (“The PTO bears
the initial burden of demonstrating that the preponderance of the evidence
establishes, prima facie, facts supporting the conclusion that the claimed
invention was on sale within the meaning of § 102(b).”).
As acknowledged by the Specification, nucleoside diphosphate is
secreted as a phosphoprotein into the extracellular environment by a variety
of human tumors (e.g. breast, lung, colon, and prostate cancer cells), and that
aggressive human tumor cells from disparate tissues were found to secrete
nucleoside diphosphate kinase-B (NDPK-B) into the extracellular
environment. The abstracts relied upon by Appellant further support the
finding that a percentage of cancers and solid tumors are known to express
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and secrete nucleoside diphosphate kinase-B. For example, Konishi teaches
that of the 80 cases of nonmetastatic prostate carcinoma examined, 60%
were immunoreactive for nm23-H2, the gene encoding NDPK-B.
It may be that not every instance in which a catechin, such as
epigallocatechin gallate, which the Specification teaches is an inhibitor of
the activity of nucleoside disphosphate kinase-B, is administered to a patient
having a cancer or a solid tumor, as taught by Morre, would result in
anticipation. But, as discussed above, the evidence shows that it is known in
the art that a variety of human tumors secrete NDPK-B into the extracellular
environment, establishing that anticipation necessarily resulted when some
percentage of Morre’s patients were treated. “Where . . . the result is a
necessary consequence of what was deliberately intended, it is of no import
that the article’s authors did not appreciate the results.” MEHL/Biophile,
192 F.3d at 1366. Anticipation does not require that Morre recognized
NDPK-B expression and secretion by the tumors to be treated. Schering
Corp. v. Geneva Pharmaceuticals, Inc., 339 F.3d 1373, 1377 (Fed. Cir.
2003).

CONCLUSION OF LAW
We conclude:
1) That the manipulative steps claimed do not differ from those
taught by Moore; and
2) Appellant has not demonstrated that the Examiner erred in finding
that Morre inherently discloses a tumor that expresses and secretes NDPK-
B.
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We thus find that Morre anticipates claim 1. As Appellant has not
argued the other rejected claims separately, we affirm the rejection of claims
2-8, 11, 12, 14, 15, 17, 18, 20-22, 24, and 25 under 35 U.S.C. § 102(b) as
being anticipated by Morre.

ISSUE (Obviousness)
The Examiner concludes that claims 10, 13, 16, 19, and 23 under 35
are rendered obvious by the combination of Morre and Castonguay.
Appellant contends Examiner has failed to establish that the ordinary
artisan would have combined Morre and Castonguay to arrive at the claimed
invention.
Thus, the issue on appeal is: Has Appellant demonstrated that the
Examiner erred in combining Morre and Castonguay?

FINDINGS OF FACT
FF14 The Examiner rejects claims 10, 13, 16, 19, and 23 under 35 U.S.C.
§ 103(a) as being obvious over the combination of Morre and Castonguay
(Ans. 3-4).
FF15 Morre is relied upon as for the anticipation rejection (id.). The
Examiner notes that Morre does not “explicitly teach that the catechin is
ellagic acid.” (Id.)
FF16 The Examiner cites Castonguay for teaching that “ellagic acid is a
breakdown product of ellagitannins and is effective at inhibiting tumor
promotion in skin tumors, as well as, lung tumorogenesis.” (Id.)
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FF17 Castonguay teaches further that ellagic acid and ellagitannins “have
different antitumorigenic and antipromoting activities.” (Castonguay,
Abstract.)
FF18 The Examiner concludes:
Thus, it would have been prima facie obvious to one of
ordinary skill in the art at the time the invention was made to
combine the teachings of the reference so as to modify the
method taught by Morre et al. to include ellagic acid in view of
the teachings of Caston[g]uay et al. One would have been
motivated to do so because Castonguay et al. teach that ellagic
acid is a breakdown product of ellagitannins and is effective at
inhibiting tumor promotion in skin tumors, as well as, lung
tumorigenesis. Thus, one of ordinary skill in the art would have
a reasonable expectation that by modifying the method taught
by Morre et al. to include ellagic acid in view of the teachings
of Caston[g]uay et al., one would achieve a method of
inhibiting tumorgenesis.

(Ans. 4.)

PRINCIPLES OF LAW
The question of obviousness is resolved on the basis of underlying
factual determinations including: (1) the scope and content of the prior art;
(2) the level of ordinary skill in the art; (3) the differences between the
claimed invention and the prior art; and (4) secondary considerations of
nonobviousness, if any. Graham v. John Deere Co., 383 U.S. 1, 17 (1966).
While the analysis under 35 U.S.C. § 103 allows flexibility in
determining whether a claimed invention would have been obvious, KSR
Int’l Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007), it still requires showing
that “there was an apparent reason to combine the known elements in the
fashion claimed by the patent at issue.” Id. “We must still be careful not to
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allow hindsight reconstruction of references to reach the claimed invention
without any explanation as to how or why the references would be combined
to produce the claimed invention.” Innogenetics, N.V. v. Abbott Labs., 512
F.3d 1363, 1374 n.3 (Fed. Cir. 2008).

ANALYSIS
Appellant argues that the Examiner has failed to establish that the
ordinary artisan would have combined Morre and Castonguay to arrive at the
claimed invention, as “Morre and Castonguay have completely different
purposes that would in no way be viewed as interchangeable by those of
skill in the art.” (App. Br. 10.)
The Court of Appeals for the Federal Circuit set forth in In re
O’Farrell, 853 F.2d 894, 903 (Fed. Cir. 1988), two situations in which an
“obvious to try” rationale was usually improperly applied. The first
situation of “what would have been ‘obvious to try’ would have been to vary
all parameters or try each of numerous possible choices until one possibly
arrived at a successful result, where the prior art gave either no indication of
which parameters are critical or no direction as to which of many possible
choices is likely to be successful.” (Id.) The second situation of “what was
‘obvious to try’ was to explore a new technology or general approach that
seemed to be a promising field of experimentation, where the prior art gave
only general guidance as to the particular form of the claimed invention or
how to achieve it.” Id. See In re Kubin, 561 F.3d 1351, 1358-60 (noting
that the rationale in O’Farrell was “affirmed in the logical inverse” in KSR,
550 U.S. at 417, in the Statement that “§103 bars patentability unless ‘the
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improvement is more than the predictable use of prior art elements according
to their established functions.’”).
Based on the above framework, we conclude that, at best, it may have
been obvious to try and substitute ellagic acid for the catechins disclosed by
Morre in the method of treating cancer and solid tumors. Castonguay
specifically teaches that ellagic acid and ellagitannins have different
antitumorigenic and antipromoting activities. Thus, we conclude that this
situation is analogous to the second situation discussed by the O’Farrell
court, wherein Morre sets forth a general approach for treating cancer or
solid tumors using catechins. There would not have been, however, a
reasonable expectation of success that the substitution of ellagic acid for the
catechin, which the prior art teaches has different activity that ellagitannins,
would have resulted in the successful treatment of cancers and solid tumors,
as set forth in Morre. See Kubin, 561 F.3d at 1361.

CONCLUSIONS OF LAW
We conclude that Appellant has demonstrated that the Examiner erred
in combining Morre and Castonguay. We thus reverse the rejection of
claims 10, 13, 16, 19, and 23 under 35 U.S.C. § 103(a) as being obvious
over the combination of Morre and Castonguay.

SUMMARY
We affirm the rejection of claims 2-8, 11, 12, 14, 15, 17, 18, 20-22,
24, and 25 under 35 U.S.C. § 102(b) as being anticipated by Morre, but
reverse the rejection of claims 10, 13, 16, 19, and 23 under 35 U.S.C.
§ 103(a) as being obvious over the combination of Morre and Castonguay.
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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
lp

DAVID L. PARKER
FULBRIGHT & JAWORSKI L.L.P.
600 CONGRESS AVENUE, SUITE 2400
AUSTIN TX 78701