Ex Parte O et al

Patent Trials and Appeals Board

Jul 1, 2019

14107751 - (D) (P.T.A.B. Jul. 1, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
14/107,751 12/16/2013
66981 7590
HUGH MCTA VISH
MCT A VISH PA TENT FIRM
7460 Pinehurst Road
Pine Springs, MN 55115
07/01/2019
FIRST NAMED INVENTOR
Timothy J. O'Brien
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.
ll0.041US1 4933
EXAMINER
REDDIG, PETER J
ART UNIT PAPER NUMBER
1642
MAIL DATE DELIVERY MODE
07/01/2019 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
Ex parte TIMOTHY J. O'BRIEN, JOHN BEARD,
and WILBUR C. HITT JR. 1
Appeal 2018-008269
Application 14/107, 7 51
Technology Center 1600
Before DONALD E. ADAMS, ERIC B. GRIMES, and
RICHARD M. LEBOVITZ, Administrative Patent Judges.
LEBOVITZ, Administrative Patent Judge.
DECISION ON APPEAL
The claims in this appeal are directed to methods of early diagnosis of
possible cancer in a patent. The Examiner rejected the claims under 35
U.S.C. § 103 as obvious and for obviousness-type double-patenting.
Pursuant to 35 U.S.C. § 134(a), Appellants appeal the Examiner's
determination that the claims are unpatentable. We have jurisdiction for the
appeal under 35 U.S.C. § 6(b). The Examiner's decision is affirmed.
1 The Appeal Brief ("Appeal Br." entered March 7, 2018) lists Bioventures,
LLC as the Real Party in Interest. Appeal Br. 4.
Appeal 2018-008269
Application 14/107, 7 51
STATEMENT OF THE CASE
Claims 1, 3, 5-7, and 3 3-51 stand rejected by the Examiner as
follows:
1. Claims 1, 3, 5-7, 33, 36, 37, and 40-51 under pre-AIA 35 U.S.C.
§ 103(a) as obvious in view of U.S. Patent No. 6,303,318 Bl (O'Brien-318),
U.S. Patent No. 4,921,790 (O'Brien-790), and U.S. Pat. Appl. 2004/0086910
Al (O'Brien-910), Mercer (Immunology Series, 1990, 53:39-54), Hornbeck
(Current Protocols in Mol. Biol., Enzyme-Linked Immunosorbent Assays
(ELISA) 2000, 11.2.1-11.2.22), and U.S. Pat. Appl. 2010/0227335 Al
(Baker). Ans. 4.
2. Claims 1, 3, 5-7, 33, 34, and 36-51 underpre-AIA 35 U.S.C.
§ 103(a) as obvious in view ofO'Brien-318, O'Brien-790, O'Brien-910,
Mercer, Hornbeck, and U.S. Patent No. 6,602,674 Bl (O'Brien-674). Ans.
8.
3. Claims 1, 3, 5-7, 33-35, and 40-51 under pre-AIA 35 U.S.C.
§ 103(a) as obvious in view ofO'Brien-790, O'Brien-910, Mercer,
Hornbeck, and WebMD
(http:/web.archive.org/web/201005211 O/http://www.webmd.com/ovarian-
cancer/guide/ovariancancerexams-and-tests, May 21, 2010). Ans. 9.
Claim 1 and other claims as unpatentable on the ground of
nonstatutory obviousness-type double patenting over the following patents
and patent applications, and further citing Diamandis (Proc. Am. Assoc.
Cancer Res., Jul. 2003, 44, Abstract 478), Mercer, Hornbeck, O'Brien-910,
O'Brien-674, WebMD, and others:
1. O'Brien-213 (U.S. Patent No. 6,316,213, claims 1-9). Ans. 13.
2. O'Brien-318(claims 1-5). Ans.17.
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Application 14/107, 7 51
3. O'Brien-790 (claims 4 and 5). Ans. 19.
4. O'Brien-818 (U.S. Patent No. 5,976,818, claims 1-4). Ans. 23.
5. O'Brien-790 ( claims 4 and 5). Ans. 25.
6. O'Brien-818 (claims 1-4). Ans. 29.
7. O'Brien-165 (U.S. Patent No. 6,268,165, claims 1-6). Ans. 32.
8. O'Brien-344 (U.S. Patent No. 6,294,344, claims 1-6). Ans. 34.
9. O'Brien-741 (U.S. Patent No. 6,649,741, claims 1-4). Ans. 37.
10. O'Brien-978 (U.S. Patent No. 6,942,978, claims 1-7). Ans. 39.
11. Underwood & O'Brien (U.S. Patent No. 7,537,901, claims 1-9).
Ans. 42.
12. O'Brien-794 (U.S. Patent No. 8,216,794, claims 1-3). Ans. 45.
13. O'Brien-674 (claims 1-5). Ans. 47.
CLAIM 1
Claim 1, which is representative of the appealed subject matter, reads
as follows:
1. A method of early diagnosis of possible cancer in a patient
compnsmg:
(a) measuring in a human blood sample protein levels of
three or more proteins selected from the group consisting of
CA125, TADG14, TADG15, TADG12, SCCE, MMP-7, ALP,
KLK6, and hepsin;
wherein the measuring is by a sandwich ELISA assay for
each of the proteins, and each sandwich ELISA assay uses a
trapping antibody against one of the proteins and a reporting
antibody against the same protein;
(b) comparing the levels of the three or more proteins to
normal range levels of the proteins to identify whether the level
of at least one of the three or more proteins is elevated, wherein
if the level of at least one of the proteins is elevated, it indicates
a possible cancer;
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Application 14/107, 7 51
wherein the three or more proteins measured (i) comprise
CA125, TADG15, and ALP, and do not comprise MMP-7, or
(ii) comprise CA125, TADG 15, TADG 14, TADG 12, and
hepsin, or (iii) comprise CA125, TADG 15, TADG 14, SCCE,
MMP-7, hepsin, and ALP; wherein the three or more proteins
do not comprise any protein not a member of the group
consisting ofCA125, TADG14, TADG15, TADG12, SCCE,
MMP-7, ALP, KLK6, andhepsin;
( c) if at least one of the levels of the three or more
proteins is elevated, conducting one or more further tests on the
human to determine if the human has cancer, wherein the
further tests comprise an imaging method selected from the
group consisting of an X-ray, a CT scan, an MRI, a PET scan,
and an ultrasound; or wherein the further tests comprise a
biopsy; and
( d) if it is determined that the human has cancer, treating
the human for cancer.
REJECTIONS
Claim 1 requires measuring three or more proteins from one of three
panels of protein markers (i, ii, or iii) ( steps (a) and (b) of claim 1) in a blood
sample using an enzyme-linked immunosorbent assay (ELISA). Step ( c)
recites that "if at least one of the levels of the three or more proteins is
elevated, conducting one or more further tests on the human to determine if
the human has cancer." The step lists the further diagnostic tests to be
conducted. Step ( d), the last step of the claim, recites that "if it is
determined that the human has cancer, treating the human for cancer."
The Examiner rejected the claims as obvious in three different
rejections based on 35 U.S.C. § 103 and thirteen obviousness-type double-
patenting rejections. Each of the rejections cited one of more patents or
patent applications to Timothy J. O'Brien (alone or with co-inventors) for
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Application 14/107, 7 51
their disclosure of the protein markers in panels (i)-(iii). Timothy J.
O'Brien is also a co-inventor of the patent application in this appeal.
The Examiner cited Mercer in each of the rejections for its disclosure
that "the use of multiple markers to create a panel of tumor markers for
diagnosis in order to improve sensitivity and specificity is known." Ans. 5.
The Examiner found that Mercer teaches that "the use of multiple markers
for cancer diagnosis provides significant gains in sensitivity for diagnosis."
Id. Based on this teaching, the Examiner found that one of ordinary skill in
the art would have been motivated to combine the various markers cited in
the O'Brien publications to improve cancer diagnostic sensitivity and
specificity, meeting the limitations of panels (i), (ii), and (iii). Ans. 7.
Mercer also discloses the marker CA125 recited in all three panels of claim
1. Ans. 6.
The Examiner further cited Hornbeck for its teaching of ELISA assays
as required by claim 1 (Ans. 6), Baker for teaching CA125 and diagnostic
tests recited in step ( c) of claim 1 (id.), WebMD for additional diagnostic
tests recited in the claims (Ans. 12), and Diamandis for describing additional
markers recited in the claims (Ans. 14). WebMD and Diamandis are not
cited in all the rejections.
The general basis for all the rejections are substantially the same with
the main differences being the protein markers cited in the different
publications.
Appellants did not provide different arguments for the obviousness
and obviousness-type double-patenting. Appeal Br. 16-22. Consequently,
we have considered all the rejections as one group.
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DISCUSSION
Early stage detection
Appellants contend that "[ n Jothing in the prior art cited says the
percentage of any marker, even CA125, present in serum in early stage
ovarian cancer patients. Nothing in the prior art cited demonstrates that any
marker other than CA125 is present or detectable in serum at all, let alone
what the normal range is or the percentage of early stage cancer or ovarian
cancer patients having it present at levels above the 95% percentile."
Appeal Br. 11.
Claim 1 is not limited to "ovarian cancer patients." Appellants are
arguing a limitation which is not found in claim 1.
With respect the arguments about "early stage" detection, there is
ample evidence in this record that establishes the need for early detection of
cancer (Dudek Deel. 2 ,-J,-J 4-6), and evidence that markers had been identified
which enabled early detection to at least some degree. For example,
O'Brien-318 discloses that its markers (which include SCCE, TADG 12,
TADG14, and Hepsin, all of which are recited in claim 1) are "for early
detection of associated ovarian and other malignancies" (Abstract), O'Brien-
790 discloses the importance of early detection and diagnosis of cancer ( col.
1, 11. 1-20), O'Brien-910 discloses that "analysis of ovarian carcinoma
subtypes, including early stage and late stage disease, confirms
overexpression of T ADG-15 [ one of the protein markers recited in claim 1]
2 Appellants provided a declaration by Arkadiusz Z. Dudek, M.D. ( executed
Feb. 23, 2017), during the prosecution of the application. Dr. Dudek states
in his declaration that he is a practicing oncologist and the Director of the
Oncology Clinical Trials Office at the University of Illinois Chicago. Dudek
Deel. 1.
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Application 14/107, 7 51
in all carcinomas examined" (ii 128), and O'Brien-213 discloses PUMP-I
[ also known as MMP-7 which is recited in claim 1] was overexpressed in
stage I carcinoma ( col. 24, 11. 24-45). Appellants in the Appeal Brief
acknowledge that that O'Brien-674 "discloses that the overexpression of
antileukoprotease is a common event in ovarian tumors, and that assays may
be developed for the early detection of ovarian cancer based on the detection
the antileukoprotease protein." Appeal Br. 16. Antileukoprotease is "ALP"
and one of the markers recited in claim 1.
To the extent that one of the specific known markers had not been
determined to be useful for early diagnosis, it would have been obvious to
determine its expression during the different cancer stages because the
skilled worker sought to identify markers for early cancer detection (Dudek
Deel. ,i,i 5, 7). As held by the U.S. Supreme Court in KSR International Co.
v. Teleflex Inc., 550 U.S. 398, 421 (2007):
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 success, it is likely the product not of
innovation but of ordinary skill and common sense. In that
instance the fact that a combination was obvious to try might
show that it was obvious under§ 103.
In this case, the markers recited in claim 1 were known at the time of
the invention and constitute a finite number of identified, predictable
solutions, namely, present or absent in early stage cancer.
Detection in serum
Appellants also argue that the markers had not been detected in serum.
Appeal Br. 11 ("It is Applicant's discovery (1) that the markers other than
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CA125 are present in serum at all."). 3
This argument is not persuasive because various publications cited in
the rejections disclose that the markers can be detected in blood, which
compnses serum:
detecting and identifying specific proteases present in the tissue
sample from the group of proteases consisting of Stratum
Comeum Chymotrytic Enzyme (SCCE) [recited in claim l],
T ADG 12 [recited in claim 1], T ADG 13, T ADG 14 [recited in
claim l], Hepsin [recited in claim l], Pump-I [also known as
MMP-7 which is recited in claim 1] Protease M.
The biological sample may be tissue, or preferably a bodily
fluid or more preferably blood or a blood component.
O'Brien-318, col. 2, 11. 62-66; col. 3, 11. 18-20 ( emphasis added).
The present invention is directed toward a method of
diagnosing cancer in an individual, comprising the steps of: (a)
obtaining a biological sample from an individual; and (b)
detecting T ADG-15 [ recited in claim 1] in the sample.
Generally, the presence of TADG-15 in the sample is indicative
of the presence of carcinoma in the individual, and the absence
of T ADG-15 in the sample is indicative of the absence of
carcinoma in the individual. Generally, the biological sample is
blood, ascites fluid, urine, tears, saliva or interstitial fluid.
O'Brien-910, ,-J 48 (emphasis added).
3 Appellants admit that the cited prior art discloses the detection of CA 125 in
serum ("O'Brien-790 discloses a method of detecting ovarian cancer
comprising contacting the serum of an individual suspected of having
ovarian cancer with an antibody against a 40 kDa subunit of CA125
(abstract and claims 4 and 5)." Appeal Br. 9. Appellants also admit that
MMP-7 had been detected in blood ("Baker discloses compositions and
methods for diagnosing ovarian cancer or identifying patients with an
increased likelihood of having ovarian cancer involving detecting MMP-7 in
the patient's blood (abstract))." Id.
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Application 14/107, 7 51
According to the above descriptions of the present invention,
representative biological samples are blood, urine, saliva, tears,
interstitial fluid, ascites fluid, tumor tissue biopsy and
circulating tumor cells. Typically, detection of the PUMP- I is
by means such as Northern blot, Western blot, PCR, dot blot,
ELIZA sandwich assay, radioimmunoassay, DNA array chips
and flow cytometry. Generally, the cancer is ovarian, breast,
lung, colon, prostate or others in which PUMP- I is
overexpressed.
O'Brien-213, col. 9, 11. 55-63 (emphasis added).
In a particular aspect of the invention, the methods comprise
obtaining a sample ( e.g., blood or serum) from a patient,
contacting the sample with at least one MMP-7 [recited in
claim 1] monoclonal antibody of the invention, and detecting
binding of the antibody to the MMP-7 protein.
Baker, ,-J 57 ( emphasis added).
Diamandis teaches that they have developed ELISA
technologies to measure the elevation of kallikreins in serum of
patients with ovarian cancer, including hK6, hK7 /SCCE
[recited in claim l], and hK8/TADG 14 [recited in claim l].
Diamandis teaches measuring either hK6, hK7 /SCCE, or
hK8/TADG 14 in combination CA125 improved the sensitivity
and specificity of CA125 area under the ROC curve in serum of
patients with ovarian cancer.
Ans. 14 ( emphasis added).
A preponderance of the evidence therefore supports the Examiner's
findings that the cited publications described the detection of the claimed
protein markers in blood or blood serum as claimed. See also Answer 60 for
additional citations to the publications relied upon by the Examiner in
making the determination that the detection of the claimed protein markers
in blood or serum was known at the time of the invention. Appellants did
not provide adequate evidence to rebut the Examiner's findings.
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Appellants contend that the disclosures referred to by the Examiner
are prophetic and that the inventors made the discovery that the claimed
markers are present in the serum. Reply Br. 7. This argument does not
persuade us that the Examiner erred. The cited prior art, as discussed above,
describes blood and serum as samples in which the recited protein markers
may be detected. The Examiner thus had a reasonable basis to find that the
markers are detectable in such fluids, shifting the burden to Appellants to
demonstrate that such conclusion is unreasonable or would not have been
credible to one of ordinary skill in the art at the time of the invention. See
M.P.E.P. § 717.07 (Ninth Edition, Revision 08.2017, last revised January
2018). Moreover, not all the disclosures are prophetic. Diamandis made
actual measurements on the serum,4 providing additional credibility to the
so-called prophetic disclosures in the O'Brien publications.
Appellants also argue that "[ n Jothing in the prior art cited
demonstrates ... what the normal range [ of the recited protein markers] is or
the percentage of early stage cancer or ovarian cancer patients having it
present at levels above the 95% percentile." Appeal Br. 11.
This argument is not persuasive. As discussed by the Examiner,
O'Brien-318 "teaches diagnosing cancer and ovarian cancer by detecting an
increase in the expression of PUMP-l/MMP-7, SCCE, hepsin, protease-
M/KLK-6, TADG 12, and/or TADG 14 protein in blood samples compared to
normal control samples. See abstract, column 2-line 49 to column 3-line 20
4 "We have recently demonstrated the multiple markers of the human
kallikrein family of serine proteases are up-regulated or down-regulated in
ovarian, breast, and other cancers and that many of them are elevated in
serum of patients with ovarian cancer."
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and claims 1-5." Final Act. 4. The Examiner also found "O'Brien-318
teaches overexpression of these markers in ovarian cancer patients, i.e.
humans. See Tables 3-7 and Figs. 1-19 and MeSH-NCBI (KLK6 protein
human, Feb. 6 1997, of record)." Final Act. 4. Thus, contrary to
Appellants' argument, the cited prior art describes determining normal
ranges and how to do so. With respect to the argument regarding "levels
above the 95% percentile," this limitation does not appear in claim 1 or any
of the dependent claims.
Panels
Appellants contend that "none" of the three specific panels "of at least
3 proteins from a list of just 9 proteins, with no other protein levels used in
the method of early diagnosis" are "suggested by any of the [ cited]
references, or even by any combination of the references." Appeal Br. 10.
Appellants argue that none of the panels described in the prior art
correspond to the panels which are recited in claim 1. Appeal Br. 9, 10.
The Examiner recognized this deficiency in the cited prior art and
cited Mercer for its teaching that "the use of multiple markers for cancer
diagnosis provides significant gains in sensitivity for diagnosis," providing a
scientific reason to have used the known cancer markers in a panel. Ans. 58.
Appellants did not identify a deficiency in this argument, and we find it
supported by a preponderance of the evidence.
Unexpected results
A showing of "unexpected results" can be used to demonstrate the
non-obviousness of the claimed invention. In re Soni, 54 F.3d 746, 750
(Fed. Cir. 1995) ("One way for a patent applicant to rebut aprimafacie case
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of obviousness is to make a showing of 'unexpected results,' i.e., to show
that the claimed invention exhibits some superior property or advantage that
a person of ordinary skill in the relevant art would have found surprising or
unexpected.").
Appellants state:
the inventors have shown surprising success in early detection
of ovarian cancer with these three sets of proteins recited in
claim 1, without looking at levels of other proteins: 79%
success with the group of CA125, TADG 15, and ALP (Table
5); 100% success with the group ofCA125, TADG15,
TADG 14, TADG 12, and hepsin (Table 2); and 86% success
with the group ofCA125, TADG15, TADG14, SCCE, MMP-7,
hepsin, and ALP (Table 6). This surprising success would rebut
any prima facie case of obviousness, had one been made.
Appeal Br. 10.
Appellants argue that it is unexpected that "overexpression of each
marker appears to be an independent event, which makes the markers a good
panel." Appeal Br. 12 (emphasis omitted). Appellants state: "Success in
detecting 79%, 100%, and 86% of early stage ovarian cancers using the
three panels, respectively, is very good success and greater than expected."
Id.
Appellants argue that the "evidence is that elevation of any one of the
proteins listed is an indication of possible cancer." Appeal Br. 13.
Appellants further state that "one aspect of the surprising result is that the
elevation of the different proteins listed is not positively correlated with each
other. Elevation of one does not make elevation of another protein more
likely; they are almost perfectly independent of each other." Id. at 13-14.
We have considered this evidence of unexpected results, but do not
find that it is sufficient to establish patentability of the claims.
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First, the Examiner provided evidence that it was known at the time of
the invention each of the recited markers, when elevated, are associated with
cancer. Ans. 4, 8, 9, 14, 23, 32, 35, 37, 40, and 43. Appellants did not
provide adequate evidence to rebut these findings, and we find the findings
fully supported by the evidence in this record.
Second, as discussed by Mercer, it was known at the time of the
invention that utilizing more than one protein for cancer detection, increased
sensitivity in detecting the cancer. Mercer discloses:
Four panels of two markers, three panels of three markers, and
two panels of four markers are presented. All panels contained
CA 125, which is considered by many investigators to be the
most sensitive ovarian marker available. In three of the seven
panels, the combination of CA 125 with DP 3, CA 19-9, or
CEA/CA 19-9 offered only minimal gains in sensitivity
( average, 6% ). However, in six panels 10% or greater increases
in sensitivity were observed when panel results were compared
to the use of CA 125 alone. Very impressive is the study of
Negishi in which a four-test combination of CA 125, TPA,
ferritin, and IAP resulted in 100% sensitivity and 100%
specificity. Also of note is the work of Ward, who found a
marked increase in sensitivity (37%) in patients with early-
stage disease when a three-test combination of CA 125,
HMFG-2, and PLAP was used.
Mercer 46 (reference citations omitted).
Thus, one of ordinary skill in the art would have reasonably expected
some gain in the sensitivity in detecting cancer from utilizing multiple
markers, and even as much as a 100% gain in some cases.
In sum, it was not unexpected that the recited markers are elevated in
cancer and that utilizing multiple markers would show a gain in sensitivity
in detecting cancers. Appellants have not established that the gain resulting
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from the claimed combination of markers is greater than would have been
expected.
Third, Appellants' arguments about "79% success with the group of
CA125, TADG 15, and ALP (Table 5); 100% success with the group of
CA125, TADG 15, TADG 14, TADG 12, and hepsin (Table 2); and 86%
success with the group ofCA125, TADG15, TADG14, SCCE, MMP-7,
hepsin, and ALP (Table 6)" is not commensurate with scope of claim 1.
Unexpected results must be "commensurate in scope with the degree of
protection sought by the claimed subject matter." In re Harris, 409 F.3d
1339, 1344 (Fed. Cir. 2005).
As discussed by the Examiner, the claims do not require that all the
protein markers be elevated, but only require measuring three protein
markers, where only one is elevated. 5 However, the data in the Specification
relied upon by Appellants bases the percent success on all markers, not just
elevation of one of the markers in the recited sets of markers.
For example, Appellants state that table 5 shows a success rate of
79%. Table 5 is reproduced below:
5 "(b) comparing the levels of the three or more proteins to normal range
levels of the proteins to identify whether the level of at least one of the three
or more proteins is elevated, wherein if the level of at least one of the
proteins is elevated, it indicates a possible cancer."
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Table 5: CA125, TADG·lS, and ALP ei
$8/70 30/39 7/8 12/lS S/9 9/9
% 79% s3% 11% 88% so% s6% 100% 1
~ ................................................. i ................................................. 1 ................................................................ i ....................... ~ ............................. 1
Table 5 lists 79% positive results for all tested stage I and II ovarian
cancer cells, based on combined over-expression of CA125, TADG-15, and
ALP. Panel (i) of claim 1 lists all three of these protein markers, but
requires elevation of only one. In contrast, the value of 79% is based on the
detection of all three proteins, not only one which is claimed.
The same difference between what is asserted as an unexpected result
( detection of all protein markers) and what is claimed ( only one of three) is
seen for panels (ii) and (iii) of claim 1.
In response to the Examiner's argument, Appellants state that the
"Examiner misunderstands the evidence and the claims." Appeal Br. 13.
Appellants argue:
The evidence and unexpected result is not that the markers are
elevated together and an elevation of three of the proteins listed
is an indication of possible cancer. The evidence is that
elevation of any one of the proteins listed is an indication of
possible cancer. And one aspect of the surprising result is that
the elevation of the different proteins listed is not positively
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correlated with each other. Elevation of one does not make
elevation of another protein more likely; they are almost
perfectly independent of each other. That is exactly what
makes these panels good panels for early detection of cancer:
that the proteins are independently elevated in cancer, and
therefore one looks for elevation of any one of the members of
each panel, not three or more of the members.
Appeal Br. 13-14.
This argument is not persuasive because the Examiner cited evidence
that the prior art had established each of the markers alone was "an
indication of possible cancer." Id. Appellants have not demonstrated a
defect in this finding. The fact that the "elevation of the different proteins
listed is not positively correlated with each other" is not persuasive as
unexpected results because only one protein needs to be elevated to meet the
limitations in the claim.
The crux of Appellants' argument appears to be based on the panel,
itself, namely that it was unexpected that each of the markers in panels (i),
(ii), and (iii) behaved independently. However, there is no persuasive
evidence in this record that such result is unexpected. Appellants did not
direct us to a statement in Dr. Dudek' s declaration that it was unexpected
that the markers in the panels behaved independently of each other.
Appellants base the independence of the markers by multiplying
probabilities, and showing that the theoretical result is in agreement with the
actual data. Appeal Br. 12.6 To the extent these calculations are correct,
6 These calculations were made in the Appeal Brief for only Table 5 and
panel (i), and not panels (ii) and (iii). Thus, even if these results were
persuasive, the independence of the protein markers has not been established
for the markers recited in panels (ii) and (iii).
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Appellants did not establish the underlying presumption upon which the
unexpected result is asserted:
One would have expected that their overexpression was
positively correlated - that overexpression of one makes
overexpression of the others more likely. That would have
made them a worse panel. But surprisingly, their expression is
not positively correlated with each other but is independent of
one another. That makes these panels better panels and is the
reason one looks for overexpression of any one marker, not
three or more. Claim 1 therefore is precisely tailored to the
unexpected result.
Appeal Br. 14.
The only evidence that it would have been expected the
overexpression of the markers would be "positively correlated" is the
attorney argument presented in the Appeal Brief.
An applicant cannot prove unexpected results with attorney
argument and bare statements without objective evidentiary
support. See In re Lindner, 59 C.C.P.A. 920,457 F.2d 506, 508
(CCPA 1972); In re Geisler, 116 F.3d 1465, 1470 (Fed. Cir.
1997) ("attorney argument [is] not the kind of factual evidence
that is required to rebut a prima facie case of obviousness"); In
re Soni, 54 F.3d 746, 750 (Fed. Cir. 1995) ("It is well settled
that unexpected results must be established by factual evidence.
Mere argument or conclusory statements ... [do] not suffice.")
(quoting In re De Blauwe, 736 F.2d 699, 705 (Fed. Cir. 1984)).
CFMT, Inc. v. Yieldup Intern. Corp., 349 F.3d 1333, 1342 (Fed. Cir. 2003).
Summary
In sum, for the reasons discussed above, and those of the Examiner,
we conclude that the evidence of unexpected results is not sufficient to
establish patentability of the claims. Obviousness rejections 1-3 are
affirmed. Obviousness-type double-patenting rejections 1-13 are affirmed.
With the exception of claim 5, which is addressed below, Appellants did not
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Appeal 2018-008269
Application 14/107, 7 51
separately argue the rejected claims. Thus, claims 1, 3, 6, 7, and 33-51 fall
with claim 1. 37 C.F.R. § 41.37( c )(1 )(iv).
Claim 5
Claim 5 depends from claim 1 and further recites "wherein the cancer
is ovarian cancer."
Appellants assert that the Examiner conceded the claims limited to
ovarian cancer show unexpected results. Appeal Br. 13. We do not agree.
The Examiner stated:
Applicant's arguments have been considered, but have not been
found persuasive. Although CA125, TADG-15 and ALP show
a greater than expected combined elevation in detection of
ovarian cancer, the claims are not limited to ovarian cancer,
rather, the claims encompass early diagnosis of any possible
cancer. Additionally, the claims only require that one of the
three proteins be elevated for an indication of a possible cancer.
Thus, the claims do not require that all three of the proteins be
elevated for the indication of cancer. The evidence of
nonobviousness must be commensurate in scope with the
claims to rebut the prima facie case of obviousness.
Final Act. 6 ( emphasis added).
Thus, the same defects as discussed above for claim 1, namely that the
asserted unexpected results are for all three proteins, but only one is
necessary to be elevated, and the failure to establish that it was unexpected
that the markers would behave independently, are present in claim 5. The
rejection of claim 5 is affirmed.
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Appeal 2018-008269
Application 14/107, 7 51
TIME PERIOD
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § l .136(a)(l )(iv).
AFFIRMED
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