Ex Parte Linder et al

Board of Patent Appeals and Interferences

Aug 25, 2009

10738018 (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.
10/738,018 12/17/2003 James Linder 11.038011 7410
38732 7590 08/26/2009
CYTYC CORPORATION
Darry Pattinson, Sr. IP Paralegal
250 CAMPUS DRIVE
MARLBOROUGH, MA 01752
EXAMINER
CANELLA, KAREN A
ART UNIT PAPER NUMBER
1643
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 JAMES LINDER and BRIAN LENTRICHIA
__________

Appeal 2008-005436
Application 10/738,018
Technology Center 1600
__________

Decided: August 26, 2009
__________

Before ERIC GRIMES, LORA M. GREEN, and JEFFREY N. FREDMAN,
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 1-16. We have jurisdiction under 35
U.S.C. § 6(b).
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STATEMENT OF THE CASE
Claims 1 and 5 are representative of the claims on appeal, and read as
follows:
1. A method for detecting biomarkers in a biological sample, comprising
the steps of:
(a) obtaining a cervical pap specimen and
(b) detecting the presence of biomarkers in said sample;
wherein the presence of said biomarkers is indicative [of] the presence of a
non-cervical cancer.

5. The method of claim 1, wherein said biomarkers are selected from the
group consisting of proteins, nucleic acids, carbohydrates, fatty acids,
glycoproteins, and lipids.

The Examiner relies on the following evidence:
Xu 5,366,866 Nov. 22, 1994
Su 2003/0138793 A1 Jul. 24, 2003

G.I. Deichman, “Natural Selection and Early Changes of Phenotype of
Tumor Cells in vivo: Acquisition of New Defense Mechanisms”, 65
Biochemistry (Moscow) no. 1, 92-111 (2000).

R. D. Athavale et al., “Psammoma bodies on postmenopausal cervical
smear a rare sinister finding”, 22 Journal of Obstetrics and Gynaecology,
260-265 (2002).

Barbara J. Guidos, “Detection of Endometrial Adenocarcinoma With the
ThiPrep® Pap Test TM”, 23 Diagnostic Cytopathology no. 4, 260-265 (2000).

Lieselot Je Lammens et al., “Abnormal glandular smear: first evidence of
ovarian malignancy”, 22 Journal of Obstetric and Gynaecology, no. 6, 702
(2002).

James Linder, M.D., M.I.A.C. et al., “The ThinPrep Pap Test A review of
Clinical Studies”, 41 Acta Cytologica no. 1, 30-38 (1997).

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The following grounds of rejection are before us for review:
I) Claims 5, 10, and 15 stand rejected under 35 U.S.C. § 112, first
paragraph, as failing to comply with the written description requirement;
II) Claims 5, 10, and 15 stand rejected under 35 U.S.C. first paragraph,
on the grounds that the Specification fails to enable the full scope of the
claimed subject matter;
III) Claims 1, 2, 7, and 12 stand rejected under 35 U.S.C. § 102(b) as
being anticipated by Athavale;
IV) Claims 1, 2, 6, 12, and 16 stand rejected under 35 U.S.C. § 102(b) as
being anticipated by Guidos;
V) Claims 1-5 and 7-10 stand rejected under 35 U.S.C. § 103(a) as being
obvious over the combination of Lammens and Su;
VI) Claims 1, 2, 6, 7, 11, 12, and 15 stand rejected under 35 U.S.C.
§ 103(a) as being obvious over the combination of Athavale and Linder; and
VII) Claims 1-5, 7-10, and 12-15 stand rejected under 35 U.S.C. § 103(a)
as being obvious over the combination of Xu, Guidos, and Lammens.
We reverse grounds I and II, but affirm grounds III-VII.

ISSUE (Written Description)
The Examiner finds that claims 5, 10, and 15 fail to comply with the
written description requirement
Appellants contend that claims 5, 10, and 15 describe genera of the
“biomarkers” recited in independent claims 1, 7, and 12.
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Thus, the issue on appeal is: Have Appellants demonstrated that the
Examiner erred in finding that dependent claims 5, 10, and 15 fail to meet
the written description requirement?

FINDINGS OF FACT
FF1 The Specification teaches that the “invention allows for the detection
of markers in a biological sample, comprising the steps of obtaining a
cervical pap specimen and detecting the presence of markers in the sample
wherein the presence of the markers is indicative of the presence of cancer.”
(Spec. 3.)
FF2 The Specification teaches:
the term “marker” or “biomarker” refers to without limitation,
organic as well as inorganic substances consisting of lipids,
lipopolysaccharides, fatty acids, carbohydrates, sugars,
proteins, glycoproteins, endogenous enzymes such as kinases,
cell membrane structures, cytoplasmic, nucleotides and nucleic
acids (i.e., DNA, RNA). The markers particularly include any
markers of diagnostic interest and especially proliferation
markers such as; hormone receptors such as estrogen receptors,
progesterone receptors or androgen receptors; cytoskeleton
compounds; hematological markers; oncogene products such as
p53; cell membrane constituents; nuclear bound receptors;
chromosomal aberrations such as gene amplifications, gene
deletions, point mutations and translocations; and infectious
agents.

(Id. at 5.)
FF3 The Examiner rejects claims 5, 10, and 15 under 35 U.S.C. § 112, first
paragraph, as failing to comply with the written description requirement
(Ans. 4).
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FF4 The Examiner finds that while proteins, nucleic acids, carbohydrates,
and glycoproteins are known to serve as biomarkers, the “teachings of the art
cannot be relied upon for the description of the fatty acid genus or the lipid
genus, wherein said genuses function [as] biomarkers for the detection of
non-cervical cancer cells in a cervical pap specimen or for the discernment
of non-cervical cells from cervical cells.” (Id.)
FF5 The Examiner notes that “the art recognizes a glycosphingolipid
which is a breast tumor antigen, however this one example does not
adequately describe an entire genus characterized only by the quality of
being a lipid.” (Id.)

PRINCIPLES OF LAW
“The burden of showing that the claimed invention is not described in
the application rests on the PTO in the first instance.” In re Edwards,, 568
F.2d 1349, 1354 (CCPA 1978). A written description of an invention
involving a chemical genus, like a description of a chemical genus, “requires
a precise definition, such as by structure, formula, [or] chemical name,” of
the claimed subject matter sufficient to distinguish it from other materials.
Fiers v. Revel, 984 F.2d 1164, 1171 (Fed. Cir. 1993).

The determination of what is needed to support generic
claims to biological subject matter depends on a variety
of factors, such as the existing knowledge in the
particular field, the extent and content of the prior art,
the maturity of the science or technology, the
predictability of the aspect at issue, and other
considerations appropriate to the subject matter.

Capon v. Eshhar, 418 F.3d 1349, 1359 (Fed. Cir. 2005).
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ANALYSIS
Appellants argue that the claimed invention is drawn to a method of
detecting a biomarker in a biological sample, not the composition of the
biomarker (App. Br. 8). Appellants argue further that claims 5, 10, and 15
describe genera of biomarkers that are indicative of the cancers recited in
independent claims 1, 7, and 12 (id.). According to Appellants, “since the
claims involved are not drawn to specific species, it is not necessary for the
Appellant to expressly name members of the genuses to comply with the
written description requirement.” (Id. at 9.)
We find that Appellants have the better argument. The independent
claims, claims 1, 7, and 12 require the step of “detecting biomarkers in said
sample,” and claims 5, 10, and 15 limit the biomarker to markers selected
from the group consisting of proteins, nucleic acids, carbohydrates, fatty
acids, glycoproteins, and lipids. While we do not necessarily disagree with
the Examiner’s findings, the Examiner has not adequately explained how the
term “biomarker” is adequately described, but the narrower genus of “fatty
acids” or the genus of “lipids” is not. The Examiner improperly places the
burden of production on Appellants, when finding that “[t]here is no art of
record which would provide evidence that such a genus of fatty acids or
lipids was well known at the time of filing” (Ans. 4). With express ipsis
verbis support for the claim language, it is the Examiner’s responsibility to
provide evidence or scientific reasoning to demonstrate the lack of
descriptive support. We are thus compelled to reverse the rejection.

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CONCLUSION OF LAW
We find that Appellants have demonstrated that the Examiner erred in
finding that dependent claims 5, 10, and 15 fail to meet the written
description requirement.
We thus are compelled to reverse the rejection of claims 5, 10, and 15
under 35 U.S.C. § 112, first paragraph, as failing to comply with the written
description requirement.

ISSUE (Enablement)
The Examiner concludes that the Specification fails to enable the full
scope of the subject matter of claims 5, 10, and 15.
Appellants contend that as the Examiner concludes that the
Specification enabled the genus of the “biomarkers” recited in independent
claims 1, 7, and 12, it also enables the genus of lipids and the genus of fatty
acids listed in dependent claims 5, 10, and 15.
Thus, the issue on appeal is: Have Appellants demonstrated that the
Examiner erred in concluding that the Specification fails to enable the full
scope of the subject matter of claims 5, 10, and 15?

FINDINGS OF FACT
FF6 The Examiner rejects claims 5, 10, and 15 under 35 U.S.C. § 112, first
paragraph, on the grounds that the Specification fails to enable the full scope
of the claimed subject matter (Ans. 4).
FF7 According to the Examiner, “the [S]pecification, while being enabling
for methods of using tumor markers which are proteins, nucleic acids,
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glycoprotein and carbohydrates, does not reasonably provide enablement for
methods of using tumor markers which are fatty acids or lipids.” (Id.)
FF8 The Examiner finds that the art does not enable “the detection of fatty
acids and lipids as tumor markers.” (Id. at 5.)
FF9 The Examiner finds further that in order to practice the full scope of
the invention, “one of skill in the art would be forced to identify ‘fatty acids’
and ‘lipids’ which differed qualitatively or quantitatively between cervical
samples including potentially malignant cervical samples, and extra cervical
samples.” (Id. at 6.)
FF10 The Examiner also finds that the Specification does not teach methods
of detecting the fatty acids and lipids with enough sensitivity so as to be
diagnostic (id.).
FF11 The Examiner cites Deichman as teaching “that tumor cells acquire
the ability to release E2 type prostaglandin [a polyunsaturated fatty acid]
upon contact with NK cells, macrophage and neutrophils.” (Id. at 5.)
FF12 The Examiner notes, however, that there are no teachings that “would
indicate that the E2 prostaglandin expression could be selectively induced in
non-cervical pap smear sample and the resulting expression could be
diagnostic for non-cervical cancer.” (Id. at 5-6.)
FF13 The Examiner concludes that “[g]iven the breadth of the claims and
the complete lack of teachings in the [S]pecification, one of skill in the art
would be subject to undue experimentation in order to make and use the
broadly claimed method.” (Id. at 6.)

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PRINCIPLES OF LAW
The Examiner bears the initial burden of showing nonenablement.
See In re Wright, 999 F.2d 1557, 1561-62 (Fed. Cir. 1993). “[E]nablement
requires that the specification teach those in the art to make and use the
invention without ‘undue experimentation.’ . . . That some experimentation
may be required is not fatal; the issue is whether the amount of
experimentation required is ‘undue.’” In re Vaeck, 947 F.2d 488, 495 (Fed.
Cir. 1991) (emphasis in original).

ANALYSIS
Appellants argue that “considering the already stipulated fact that
the[re] are a number of protein, nucleic acid, and carbohydrate cancer
markers, one of skill in the art would easily be able to identify the presence
of fatty acid or lipid biomarkers (aside from the two previously identified) in
a cervical pap specimen.” (App. Br. 11.)
We conclude that Appellants have the better argument. As discussed
above with respect to the written description rejection, the independent
claims, claims 1, 7, and 12 require the step of “detecting biomarkers in said
sample,” and claims 5, 10, and 15 limit the biomarker to markers selected
from the group consisting of proteins, nucleic acids, carbohydrates, fatty
acids, glycoproteins, and lipids. The Examiner has not adequately explained
how the term “biomarker” is adequately enabled, but the narrower genus of
“fatty acids” or the genus of “lipids” are not. We are thus compelled to
reverse the rejection.

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CONCLUSION OF LAW
We conclude that Appellants have demonstrated that the Examiner
erred in concluding that the Specification fails to enable the full scope of the
subject matter of claims 5, 10, and 15.
We are thus compelled to reverse the rejection of claims 5, 10, and 15
under 35 U.S.C. first paragraph, on the grounds that the Specification fails to
enable the full scope of the claimed subject matter

ISSUE (Anticipation)
The Examiner finds that claims 1, 2, 7, and 12 are anticipated by
Athavale; and that claims 1, 2, 6, 12, and 16 are anticipated by Guidos.
Appellants contend that neither Athavale nor Guidos teaches a
diagnostic marker.
Thus, the issue on appeal is: Have Appellants demonstrated that the
Examiner erred in finding that Athavale and Guidos teach detecting a
biomarker?

FINDINGS OF FACT
FF14 The Examiner rejects claims 1, 2, 7, and 12 under 35 U.S.C. § 102(b)
as being anticipated by Athavale (Ans. 6).
FF15 The Examiner finds that Athavale discloses “the detection of
psammoma bodies in a cervical smear as being indicative of ovarian and
endometrial cancer in postmenopausal women.” (Id. at 7.)
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FF16 Athavale teaches that psammoma bodies are laminated calcospherites
that are found in association with both benign and malignant conditions of
the female genital tract (Athavale, Abstract).
FF17 The Examiner interprets biomarker, based on the teachings of the
Specification, as any marker of diagnostic interest (Ans. 16).
FF18 The Examiner rejects claims 1, 2, 6, 12, and 16 under 35 U.S.C.
§ 102(b) as being anticipated by Guidos (Ans. 7).
FF19 The Examiner finds that Guidos teaches “the detection of endometrial
endocarcinoma by the ThinPrepTM PaP Test,” noting that the “detection
[of] endometrial adenocarcinoma cells per se fulfill the limitation of
detecting endometrial cancer biomarkers in a pap smear.” (Id.)
FF20 Guidos teaches that the cells from endometrial adenocarcinoma are
identified by established cytological features, such as the size and shape of
the cell (Guidos, p. 262, second column). Guidos teaches that in well-
differentiated adenocarcinomas, the nuclei are hyperchromatic, with
irregularly shaped chromatin and micronucleoli, whereas in poorly
differentiated adenocarcinomas, the cells contain macronucleoli, the
cytoplasm is finely vacuolated and the nuclei are eccentrically located within
the cytoplasm (Id. at p. 262, second column-p. 263, first column).

PRINCIPLES OF LAW
It is axiomatic that in order for a prior art reference to serve as an
anticipatory reference, it must disclose every limitation of the claimed
invention, either explicitly or inherently. In re Schreiber, 128 F.3d 1473,
1477 (Fed. Cir. 1997).
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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). Ultimately, “absent claim language carrying a narrow meaning, the
PTO should only limit the claim based on the specification . . . when [it]
expressly disclaim[s] the broader definition.” In re Bigio, 381 F.3d 1320,
1325 (Fed. Cir. 2004); see also, In re Paulsen, 30 F.3d 1475, 1480 (Fed. Cir.
1994) (“Although an inventor is indeed free to define the specific terms used
to describe his or her invention, this must be done with reasonable clarity,
deliberateness, and precision.”).
We further decline to read limitations from the Specification into the
claims, a practice that the Court of Appeals for the Federal Circuit, our
reviewing court, cautions against. See SuperGuideCorp. v. DirecTV
Enterprises, Inc., 358 F.3d 870, 875, (Fed. Cir. 2004) (“Though
understanding the claim language may be aided by explanations contained in
the written description, it is important not to import into the claim limitations
that are not part of the claim. For example, a particular embodiment
appearing in the written description may not be read into a claim when the
claim language is broader than the embodiment.”).

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ANALYSIS
Appellants argue that Athavale does not anticipate the rejected claims
as Athavale detects the presence of psammoma bodies, which are calcium
deposits, and the skilled artisan would not consider a calcium deposit to be a
biomarker (App. Br. 16). In support of that argument, Appellants cite page 2
of the Specification (see FF 2), asserting that “[n]owhere in the
[S]pecification is it contemplated that calcium deposits could be considered
as ‘biomarkers.’” (App. Br. 17.)
Appellants also argue that Guidos does not anticipate the rejected
claims, as Guidos detects cancerous cells in a pap smear, and that
“[c]ancerous cells cannot be considered biomarkers since they are cancerous
themselves.” (App. Br. 18.) Appellants again cite page 2 of the
Specification as defining biomarkers, asserting that the ordinary artisan
“would recognize that a ‘biomarker’ is a distinctive biological or
biologically derived indicator (such as a metabolite) of a process, event, or
condition (such as cancer).” (Id. at 19.) Appellants thus assert that “a
marker for the detection of cancer would not be a cancer cell itself, but
another biological molecule which is an indicator of the presence of a cancer
cell(s) in a human body.” (Id.)
Appellants’ arguments have been considered, but are not found to be
convincing. The Specification notes the “term ‘marker’ or ‘biomarker’
refers to without limitation, organic as well as inorganic substances . . . .
The markers particularly include any markers of diagnostic interest . . . .”
(See FF 2). Thus, the examples provided by the Specification of a “marker”
or “biomarker” are merely that, examples. The Specification does not limit
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“marker” or “biomarker” to the specifically recited substances, and we also
decline to do so. Thus, giving “biomarker” the broadest reasonable
interpretation in light of the teachings of the Specification, we agree with the
Examiner that a biomarker is any marker of diagnostic interest.
Thus, we find that the psammoma bodies of Athavale are
“biomarkers” because, as found by the Examiner, they are indicative of
ovarian and endometrial cancer in postmenopausal women. Moreover, as
set forth by the Specification, a “biomarker” may be an inorganic substance.
Similarly, with respect to Guidos, the endometrial carcinoma cells are
indicative of the presence of endometrial cancer, and are thus encompassed
by the term “biomarker.”

CONCLUSIONS OF LAW
We find that Appellants have not demonstrated that the Examiner
erred in finding that Athavale and Guidos teach detecting a biomarker.
We thus affirm the rejection of claims 1, 2, 7, and 12 under 35 U.S.C.
§ 102(b) as being anticipated by Athavale; as well as the rejection of claims
1, 2, 6, 12, and 16 under 35 U.S.C. § 102(b) as being anticipated by Guidos.

ISSUE (Obviousness)
The Examiner concludes that claims 1-5 and 7-10 are rendered
obvious by the combination of Lammens and Su; that claims 1, 2, 6, 7, 11,
12, and 15 are rendered obvious by the combination of Athavale and Linder;
and that claims 1-5, 7-10, and 12-15 are rendered obvious by the
combination of Xu, Guidos, and Lammens.
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Appellants contend that there is no particular suggestion in the art to
make the specific combinations as set forth by the Examiner, and that at
best, the obviousness rejection set forth an “obvious to try” rationale.
Thus, the issue on Appeal is: Have Appellants demonstrated the
Examiner erred in combining the references as set forth in the rejections on
appeal to arrive at the invention as claimed?

FINDINGS OF FACT
FF21 The Examiner rejects claims 1-5 and 7-10 under 35 U.S.C. § 103(a) as
being obvious over the combination of Lammens and Su (Ans. 7).
FF22 Lammens is cited by the Examiner for teaching “the detection of
adenocarcinoma cells in cervical pap smears.” (Id.)
FF23 The Examiner notes that Lammens teaches that further evaluation is
needed to rule out cervical carcinoma, as ovarian cancer, fallopian tube
cancer, gastrointestinal cancer, metastatic breast cancer, and peritoneal
cancer can all give rise to an abnormal glandular smear, and can all
contribute to an abnormal cervical smear (id. at 7-8; see Lammens,
Abstract).
FF24 The Examiner relies on Lammens for teaching that “while a cervical
smear suggestive [o]f carcinoma usually represents a cervical malignancy,
other malignancies should be excluded.” (Ans. 8.)
FF25 The Examiner cites Su for teaching “a method for identifying an
origin of a tumor comprising detecting and [sic, an] expression level of at
least one gene that is diagnostic for a tumor class.” (Id.)
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FF26 The Examiner also cites Su for teaching that an antibody or mRNA
may be used to detect expression levels (id.).
FF27 The Examiner concludes that it would have been obvious to the
ordinary artisan at the time of invention “to screen cervical pap smear
samples for the presence of non-cervical cancer using the methods of Su”
because Lammens teaches “the need to investigate patients with an abnormal
cervical smear.” (Ans. 8.)
FF28 The Examiner also concludes that that the ordinary artisan “would
understand that having the probes and methods of Su . . . would enable
detection of the origin of the abnormal cells and be easier and quicker than
other invasive techniques.” (Id. at 8-9.)
FF29 The Examiner rejects claims 1, 2, 6, 7, 11, 12, and 15 under 35 U.S.C.
§ 103(a) as being obvious over the combination of Athavale and Linder
(Ans. 9).
FF30 The Examiner finds that Athavale discloses “the detection of
psammoma bodies in a cervical smear as being indicative of ovarian and
endometrial cancer in postmenopausal women.” (Id. at 9.)
FF31 The Examiner notes that Athavale does not “teach a cervical scraping
collected for liquid based cytology.” (Id.)
FF32 The Examiner relies on Linder for teaching “the thin Prep Pap Test
which is a collection of cervical scraping for liquid-based cytology,” which
provides increased sensitivity and clear presentation of cells, thus facilitating
the identification of small lesions (id.).
FF33 The Examiner concludes that it would have been obvious to the
ordinary artisan to use the ThinPrep Method of Linder in preparing the
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cervical scrapings of Athavale because of the advantages of the ThinPrep
Method taught by Linder (Ans. 9).
FF34 The Examiner rejects claims 1-5, 7-10, and 12-15 under 35 U.S.C.
§ 103(a) as being obvious over the combination of Xu, Guidos, and
Lammens (Ans. 10).
FF35 The Examiner cites Xu for teaching a method of detecting breast and
endometrial cancer by assaying for proteins that bind to the monoclonal
antibodies, OXA and OXB (id.).
FF36 The Examiner notes that Xu teaches that the antibodies may be used
in immunohistochemical staining of tumor tissue (id.). The Examiner
further relies on Xu for teaching that the antibodies may be used to detect
antigen in biological fluids such as serum, blood, and ascites (id.).
FF37 Lammens (FF22-FF24) and Guidos (FF19-FF20) are relied upon as
set forth above (Ans. 10-11).
FF38 The Examiner concludes that it would have been obvious to the
ordinary artisan at the time of invention to detect antigens bound by OXA
and OXB as taught by Xu in cervical pap samples because Lammens teaches
that extra-cervical cancers, including ovarian and breast cancer, can be a
source of abnormal cells in a pap smear, as well as the teaching of Guidos
regarding the detection of endometrial cancers by a cervical smear (id. at
11).

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;
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(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).
The Supreme Court has recently emphasized that “the [obviousness] analysis
need not seek out precise teachings directed to the specific subject matter of
the challenged claim, for a court can take account of the inferences and
creative steps that a person of ordinary skill in the art would employ.” KSR
Int’l v. Teleflex Inc., 550 U.S. 398, 418 (2007). See also id. at 421 (“A
person of ordinary skill is also a person of ordinary creativity, not an
automaton.”). “The combination of familiar elements according to known
methods is likely to be obvious when it does no more than yield predictable
results.” Id. at 416. Moreover, an “[e]xpress suggestion to substitute one
equivalent for another need not be present to render such substitution
obvious.” In re Fout, 675 F.2d 297, 301 (CCPA 1982).

ANALYSIS
As to the rejection over Lammens and Su, Appellants argue, citing In
re Dembiczak, 175 F.3d 994, 999 (Fed. Cir. 1999) that “a claim rejection
must provide a specific motivation in the art for combining elements from
cited art in order to establish obviousness of a new combination.” (App. Br.
21-22.) According to Appellants, the Examiner’s rejection “does not
provide the clear, particular suggestion in the art for making the specific
claimed combination as is required.” (Id. at 24.) Appellants assert that
neither Lammens nor Su teach or suggest the detection of a biomarker in a
pap smear, therefore, as “the Examiner has not provided the clear suggestion
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in the art for the detection of biomarkers in a pap smear, a prima facie case
of obviousness has not been established.” (Id. at 24-25.) At most,
Appellants argue, the Examiner has set forth an “obvious to try” rationale,
which is not sufficient to establish obviousness (id. at 25).
Appellants argue further that the combination does not establish a
reasonable expectation of success (id.). Appellants assert that Lammens
describes the detection of abnormal cells in a pap smear, but does not
provide an “expectation that the detection of abnormal cells . . . would be
successfully used as a diagnostic agent to the detection of non-cervical
cancers.” (Id. at 26.) Appellants argue further that “there would be no
expectation that the markers described in Su . . . could be used in a cervical
pap smear.” (Id.)
Finally, Appellants argue that the combination does not teach all of
the claim limitations, as neither reference teaches that the presence of a
biomarker in a cervical pap specimen is indicative of the presence of non-
cervical cancer. Appellants assert that they define biomarker on page 2 of
the Specification (FF 2), thus clearly setting out what species are
encompassed by the term “biomarker.”
Appellants’ arguments have been carefully considered, but are not
convincing. First, as set forth with respect to the anticipation rejection, the
term of “biomarker” has been interpreted as being any marker of diagnostic
interest, which would include the adenocarcinoma cells detected in the
cervical pap smear as taught by Lammens.
Second, Appellants are apparently arguing that as the references relied
upon in making the rejection are required to set forth a specific teaching,
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suggestion, or motivation to combine. The Supreme Court, however, in
KSR, rejected a rigid application of the teaching-suggestion-motivation test.
The Court recognized that it is often necessary to look at the interrelated
teaches of multiple references; the effects of demands of the marketplace;
and the background knowledge possessed by a person of ordinary skill, “all
in order to determine whether there was an apparent reason to combine the
known elements in the fashion claimed.” 550 U.S. at 418. Moreover, the
“obviousness analysis cannot be confined by a formalistic conception of the
words teaching, suggestion, or motivation, or by overemphasis on the
importance of published articles and explicit content of issued patents.” Id.
at 419.
As set forth by the Examiner, Lammens teaches the detection of
adenocarcinoma cells in cervical pap smears, but teaches that while a
cervical smear suggestive of carcinoma usually represents a cervical
malignancy, other malignancies should be excluded. Su teaches a method of
identifying the origin of a tumor by detecting the expression level of a gene
that is diagnostic for a tumor class. Thus, we agree with the Examiner that it
would have been obvious to the ordinary artisan to look at expression levels
of genes diagnostic of a tumor class to identify the origin of any
adenocarcinoma cells detected using the method of Lammens. Moreover, it
would have been well within the level of skill of the ordinary artisan to
determine which genes are diagnostic of a tumor class. This suffices for a
reasonable expectation of success.
As to the rejection over Athavale and Linder, Appellants again argue
that the Examiner has not set forth “the clear, particular suggestion in the art
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for making the specific combination as is required.” (App. Br. 29.)
Appellants also argue that Athavale does not teach the detection of
biomarkers in a Pap smear, and that the Examiner has relied on improper
hindsight “to provide random elements of the claim.” (Id. at 30.) At best,
Appellants assert, the Examiner has set forth an obvious to try rationale (id.).
Appellants’ arguments are again not convincing. As set forth above,
“biomarker” has been broadly interpreted as any marker of diagnostic
interest, which would include the psammoma bodies of Athavale. In
addition, Appellants have not demonstrated any error in the Examiner’s
reason for combining the references, except for arguing that the Examiner
has not set forth the clear, particular suggestion in the art for making the
specific combination as is required. As noted above, such a rigid application
of the teaching-suggestion-motivation test was rejected in KSR. Moreover,
while Appellants invoke “obvious to try,” they do not point out how the
Examiner erred in combining the references such that it was an improper
application of an “obvious to try” rationale. See, e.g., In re Kubin, 561 F.3d
1351, 1358-60 (noting that the “obvious to try” 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 improvement is more than the
predictable use of prior art elements according to their established
functions.’”); In re O’Farrell, 853 F.2d 894, 903 (Fed. Cir. 1988) (setting
forth two situations in which an “obvious to try” rationale was usually
improperly applied).
As to the rejection over Xu, Guidos, and Lammens, Appellants again
argue that the Examiner has not set forth “the clear, particular suggestion in
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the art for making the specific combination as is required.” (App. Br. 31.)
Appellants also argue that Lammens teaches the detection of malignant cells
in a pap smear, but does not teach the detection of biomarkers (id. at 32).
Appellants assert that the Examiner has relied on improper hindsight “to
provide random elements of the claims.” (Id. at 32.) At best, Appellants
assert, the Examiner has set forth an obvious to try rationale (id.). These
arguments are not found to be convincing for the reasons set forth above
with respect to the previous two combinations.

CONCLUSIONS OF LAW
We conclude that Appellants have not demonstrated the Examiner
erred in combining the references as set forth in the rejections on appeal to
arrive at the invention as claimed.
We thus affirm the rejection of claims 1-5 and 7-10 under 35 U.S.C.
§ 103(a) as being obvious over the combination of Lammens and Su; the
rejection of claims 1, 2, 6, 7, 11, 12, and 15 under 35 U.S.C. § 103(a) as
being obvious over the combination of Athavale and Linder; and the
rejection of claims 1-5, 7-10, and 12-15 under 35 U.S.C. § 103(a) as being
obvious over the combination of Xu, Guidos, and Lammens.

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SUMMARY
We reverse the rejection of:
Claims 5, 10, and 15 under 35 U.S.C. § 112, first paragraph, as failing
to comply with the written description requirement; and
Claims 5, 10, and 15 under 35 U.S.C. first paragraph, on the grounds
that the Specification fails to enable the full scope of the claimed subject
matter.
We affirm the rejection of:
Claims 1, 2, 7, and 12 under 35 U.S.C. § 102(b) as being anticipated
by Athavale;
Claims 1, 2, 6, 12, and 16 under 35 U.S.C. § 102(b) as being
anticipated by Guidos;
Claims 1-5 and 7-10 under 35 U.S.C. § 103(a) as being obvious over
the combination of Lammens and Su;
Claims 1, 2, 6, 7, 11, 12, and 15 under 35 U.S.C. § 103(a) as being
obvious over the combination of Athavale and Linder; and
Claims 1-5, 7-10, and 12-15 under 35 U.S.C. § 103(a) as being
obvious over the combination of Xu, Guidos, and Lammens.

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

Appeal 2008-005436
Application 10/738,018

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