Ex Parte Mertz et al

Board of Patent Appeals and Interferences

Feb 27, 2009

10235079 (B.P.A.I. Feb. 27, 2009)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte JANET E. MERTZ, STEPHEN D. JOHNSTON,
RICHARD J. KRAUS, and ERIC A. ARIAZI
__________

Appeal 2008-3751
Application 10/235,079
Technology Center 1600
__________

Decided: 1February 27, 2009
__________

Before DONALD E. ADAMS, LORA M. GREEN, and
RICHARD M. LEBOVITZ, Administrative Patent Judges.

GREEN, Administrative Patent Judge.

DECISION ON APPEAL

1 The two-month time period for filing an appeal or commencing a civil
action, as recited in 37 C.F.R. § 1.304, begins to run from the decided date
shown on this page of the decision. The time period does not run from the
Mail Date (paper delivery) or Notification Date (electronic delivery).
Appeal 2008-3751
Application 10/235,079

2
This is a decision on appeal under 35 U.S.C. § 134 from the
Examiner’s final rejection of claims 1-5 and 7-10. We have jurisdiction
under 35 U.S.C. § 6(b).
STATEMENT OF THE CASE
The claims are directed to a method for determining breast cancer
prognosis and a method of categorizing breast cancer patients based on
expression of ERRα. Claims 1 and 2 are representative of the claims on
appeal, and read as follows:
1. A method for determining breast cancer prognosis, comprising the
steps of:
determining the level of estrogen-related receptor (ERR) α expression
in breast cancer cells of a breast cancer patient; and
comparing the ERRα level of the patient to a median ERRα level of a
suitable number of breast cancer patients as expressed in their breast cancer
cells wherein, on average, breast cancer patients with an ERRα level higher
than the median level have a shorter survival time than breast cancer patients
with an ERRα level lower than the median level.

2. A method for categorizing breast cancer patients based on ERRα
status comprising the steps of measuring the expression level of ERRα in the
breast cancer cells of a breast cancer patient and determining whether the
expression level is high or low by comparing the ERRα level of the patient
to a median ERRα level of a suitable number of breast cancer patients as
expressed in their breast cancer cells.

The Examiner relies on the following references:
Chun Yang et al. (Yang), "Modulation of Aromatase Expression in the
Breast Tissue by ERRα Orphan Receptor," 58 CANCER RESEARCH 5695-00
(1998)

Gary M. Clark, Ph.D. and William L. McGuire, M.D. (Clark), "Prognostic
factors in primary breast cancer," 3 BREAST CANCER RESEARCH AND
TREATMENT 69-72 (1983)

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Michele Relf et al. (Relf), "Expression of the Angiogenic Factors Vascular
Endothelial Cell Growth Factor, Acidic and Basic Fibroblast Growth Factor,
Tumor Growth Factor ß-1, Platelet-derived Endothelial Cell Growth Factor,
Placenta Growth Factor, and Pleiotrophin in Human Primary Breast Cancer
and Its Relation to Angiogenesis," 57 CANCER RESEARCH 963-69 (1997)
Toshiaki Utsumi et al. (Utsumi), "Correlation of Cyclin D1 MRNA Levels
With Clinico-Pathological Parameters and Clinical Outcome in Human
Breast Carcinomas," 89 INT. J. CANCER (PRED. ONCOL.) 39-43 (2000)
Takashi Suzuki et al. (Suzuki), "Estrogen-Related Receptor α in Human
Breast Carcinoma as a Potent Prognostic Factor," 64 CANCER RESEARCH
4670-76 (2004)
Jean-Marc Vanacker et al. (Vanacker), "Transcriptional targets shared by
estrogen receptor-related receptors (ERRs) and estrogen receptor (ER) α, but
not by ERß," 18 THE EMBO JOURNAL 4270-79 (1999)
Desheng Lu et al. (Lu), "Transcriptional Regulation of the Estrogen-
inducible pS2 Breast Cancer Marker Gene by the ERR Family of Orphan
Nuclear Receptors," 61 CANCER RESEARCH 6755-61 (2001)
Zhiping Zhang and Christina T. Teng (Zhang), "Estrogen receptor α and
estrogen receptor-related receptor α1 compete for binding and coactivator,"
172 MOLECULAR AND CELLULAR ENDOCRINOLOGY 223-33 (2001)

We reverse.

ISSUE
The Examiner concludes that claims 1-5 and 7 are rendered obvious
by the combination of Yang, Clark, and Relf or Utsumi.
Appellants contend that the combination as set forth by the Examiner
does not render the claimed invention obvious, and in particular, the
combination does not render obvious the limitation of “comparing the ERRα
level of the patient to a median ERRα level of a suitable number of breast
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cancer patients as expressed in their breast cancer cells” (claim 1), nor the
limitation of “determining whether the expression level is high or low by
comparing the ERRα level of the patient to a median ERRα level of a
suitable number of breast cancer patients as expressed in their breast cancer
cells” (claim 2).
Thus, the issue on Appeal is: Has the Examiner established that the
limitations of “comparing the ERRα level of the patient to a median level of
a suitable number of breast cancer patients as expressed in their breast
cancer cells” (claim 1) and “determining whether the expression level is high
or low by comparing the ERRα level of the patient to a median ERRα level
of a suitable number of breast cancer patients as expressed in their breast
cancer cells” (claim 2) are rendered obvious by the combination of
references as set forth by the Examiner?

FINDINGS OF FACT
FF1 The Examiner rejects claims 1-5 and 7-10 under 35 U.S.C. § 103(a) as
being rendered obvious by the combination of Yang, Clark, and Relf or
Utsumi (Ans. 4).
FF2 Yang is the only reference cited by the Examiner that discusses
ERRα.
FF3 The Examiner cites Yang for teaching the detection of ERRα-1
mRNA in breast cancer tissue by RT-PCR, and that ERRα-1 is expressed at
higher levels in cancer tissue (id. (citing Yang p. 5697, right column, second
paragraph)).
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FF4 The Examiner finds that Yang teaches “that the expression of ERRα-1
is upregulated by estrogen in mouse uterus and ERRα-1 modulates the
activation effect on estrogen on a number of gene promoters by both direct
DNA-binding competition and through ER-ERR-1 protein-protein
interaction.” (Ans. 4 (citing Yang, p. 5699, left column, lines 26-32).)
FF5 The Examiner finds further that Yang teaches that aromatase is
expressed at higher levels in breast cancer tissue than non-cancerous tissue,
and that “ERRα-1 can modulate aromatase expression/estrogen
biosynthesis.” (Ans. 4-5 (citing Yang, p. 5699, right column, first
paragraph).)
FF6 The Examiner also finds that Yang teaches of the ability of ERRα-1 to
interact with ER, as well as its ability to modulate aromatase expression and
estrogen biosynthesis, ERRα -1 could be crucial in normal breast
development, and may play an important role in the pathogenesis and
maintenance of breast cancer (Ans. 5 (citing Yang, p. 5699, right column,
first paragraph, and p. 5700, left column, second paragraph)).
FF7 According to the Examiner:
Based on the teachings of the prior art that estrogen, ER and
aromase [sic, aromatase] all play important role in the
pathogenesis of breast cancer, and ER is a prognostic marker
for breast cancer, further in view of the teaching of Yang's
reference that ERRα directly modulates estrogen synthesis and
ER action, one skilled in the art would have been motivated to
use ERRα-1 or ERRα-1 in combination with ERα as a
prognostic marker for predicting the survival of breast cancer
patients or response to hormonal treatment.

(Ans. 10.)
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FF8 The Examiner notes that Yang does not teach the use of ERRα-1 as a
prognostic indicator for breast cancer, or its use in categorizing breast
cancer, and also fails to teach comparing levels of ERRα-1 in a breast cancer
patient to median levels of breast cancer patients (Ans. 5).
FF9 The Examiner cites Clark for teaching that ERα is a prognostic
indicator of breast cancer, and for teaching that several prognostic indicators
may be used simultaneously (id.)
FF10 The Examiner cites Relf and Utsumi to demonstrate that comparing
the levels of a cancer marker in a cancer patient to the median level in cancer
patients in determining cancer patients is well known in the art (Ans. 5).
FF11 The Examiner concludes that it would have been obvious to use ERRα
for the prognosis and categorizing of breast cancer because Yang teaches
“that ERRα-1 modulates aromatase expression/estrogen biosynthesis, and
may play [an] important role in the pathogenesis and maintenance of breast
cancer, and further in view of the fact that estrogen, ERα and aromatase all
play important role in the pathogenesis of breast cancer, and Clark [ ]
teach[es] that ERα is a well-known prognostic marker for breast cancer and
can be used together with other prognostic factor for prognosis of breast
cancer.” (Id. at 6.)

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
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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, ___, 127 S. Ct. 1727, 1741 (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 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
Appellants argue that the combination of references as set forth by the
Examiner does not render the claimed invention obvious (App. Br. 9).
Appellants argue that the markers of Relf and Utsumi are unrelated to
ERRα, and thus comparing the markers to median levels in breast cancer
patients as taught by those two references cannot be extrapolated to ERRα
(id. at 19).
We conclude that Appellants have the better argument. Yang is the
only reference that discusses ERRα (FF2). As noted by the Examiner, Yang
teaches that ERRα-1 is present in higher amounts in cancerous breast tissues
than in non-cancerous tissues (FF3). We also agree that Yang teaches the
ability of ERRα-1 to interact with ER, as well as its ability to modulate
aromatase expression and estrogen biosynthesis (FF6), but at best, we
conclude that it would suggest comparing the levels of ERRα in cancerous
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tissue to non-cancerous tissue, not comparing levels to median levels in
cancerous tissue from other breast cancer patients. Relf and Utsumi do not
make up that deficiency because, as noted by Appellants, they are unrelated
to ERRα.
We acknowledge that it may have been “obvious to try” comparing
the amount of ERRα to median levels in cancerous tissue from other breast
cancer patients based on the teachings of Rel and Utsumi, and acknowledge
that “obvious to try” is sometimes sufficient to support a conclusion of
obviousness. KSR, 127 S. Ct. at 1742. However, the Court states that
“obvious to try” may be sufficient when there is
a design need or market pressure to solve a problem and there
are a finite number of identified, predictable solutions, a person
of ordinary skill has good reason to pursue the known options
within his or her technical grasp. If this leads to the anticipated
technical success, it is likely the product not of innovation but
of ordinary skill and common sense.
Id. at 1742. As Yang is the only reference that discusses ERRα, as the
mechanisms underlying cancer are very unpredictable, and as the Examiner
has not established that the markers of Relf and Utsumi are related to ERRα,
we conclude that the Examiner has not established that the combination sets
forth a predictable solution that would lead to anticipated technical success.

CONCLUSIONS OF LAW
We conclude that the Examiner has not established that the limitations
of “comparing the ERRα level of the patient to a median ERRα level of a
suitable number of breast cancer patients as expressed in their breast cancer
cells” (claim 1) and “determining whether the expression level is high or low
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by comparing the ERRα level of the patient to a median ERRα level of a
suitable number of breast cancer patients as expressed in their breast cancer
cells” (claim 2) are rendered obvious by the combination of references as set
forth by the Examiner.
We thus reverse the rejection of claims 1-5 and 7-10 under 35 U.S.C.
§ 103(a) as being rendered obvious by the combination of Yang, Clark, and
Relf or Utsumi.

REVERSED

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