Ex Parte Fung

Patent Trial and Appeal Board

Mar 29, 2017

12422530 (P.T.A.B. Mar. 29, 2017)

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.
12/422,530 04/13/2009 Eric T. Fung 052903.00102 6863
78905 7590 03/31/2017
Saul Ewing LLP (Philadelphia)
Attn: Patent Docket Clerk
Centre Square West
1500 Market Street, 38th Floor
Philadelphia, PA 19102-2186
EXAMINER
YAO, LEI
ART UNIT PAPER NUMBER
1642
NOTIFICATION DATE DELIVERY MODE
03/31/2017 ELECTRONIC
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.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
following e-mail address(es):
patents@saul.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte ERIC T. FUNG1
Appeal 2016-004829
Application 12/422,530
Technology Center 1600
Before ULRIKE W. JENKS, RICHARD J. SMITH,
and JOHN E. SCHNEIDER, Administrative Patent Judges.
SCHNEIDER, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35U.S.C. § 134 involving claims to methods
for identifying patients with ovarian cancer, which have been rejected as
being directed to non-statutory subject matter and as obvious. We have
jurisdiction under 35 U.S.C. § 6(b).
We affirm.
STATEMENT OF THE CASE
The Specification describes a method for determining the prognosis of
patients with ovarian cancer. Spec. 1,11. 12—13. The method involves
1 Appellant identifies the Real Party in Interest as Vermillion, Inc. Br. 2.
Appeal 2016-004829
Application 12/422,530
measuring biomarkers in a sample taken from a patient and then correlating
the levels of the biomarker with the duration of ovarian cancer survival.
Spec. 1,11. 12-15.
Claims 1, 17, 29, 31, 55, and 60 are on appeal. Claim 1 is
representative of the rejected claims and reads as follows:
1. A method of identifying a subject for referral to a gynecologic
oncologist, comprising:
(a) using mass spectroscopy or immunoassay to
determine the concentration or expression levels or peak
intensity values of biomarkers transthyretin (TTR) and-beta-2
microglobin (B2M) in a sample from the subject;
(b) correlating the measurements with ovarian cancer
patient length of survival, wherein the expression or up-
regulation of beta-2 microglobulin and the down-regulation of
transthyretin is indicative of short survival; and
(c) identifying a subject having a short survival time for
referral to a gynecologic oncologist.
The claims stand rejected2 as follows:
Claims 1, 17, 29, 31, 55, and 60 have been rejected under 35 U.S.C.
§ 101 as being directed to non-statutory subject matter.3
2 The pending claims were also rejected for obviousness-type double
patenting over then pending applications 11/922,621, 12/384,246, and
13/909,022. Final Act. 2. The cited applications have since been abandoned
rendering these rejections moot.
3 Claim 18 was rejected in the Final Office action, however, Appellant
cancelled claim 18 when the Appeal Brief was submitted. Br. 2—3.
2
Appeal 2016-004829
Application 12/422,530
Claims 1, 29, 31, 55, and 60 have been rejected under 35 U.S.C.
§ 103(a) as unpatentable over Zhang4 as evidenced by SGO.5
Claims 1, 17, 29, 31, 55, and 60 have been rejected under 35 U.S.C.
§ 103(a) as unpatentable over Zhang as evidenced by SGO in view of
Engel.6
Claims 1, 29, 55, and 60 have been rejected under 35 U.S.C. § 103(a)
as unpatentable over Kozak7 or Gericke8 in view of Hemadi9 or Ozguroglu10
as evidenced by SGO.
Claims 1, 17, 29, 31, 55, and 60 have been rejected under 35 U.S.C.
§ 103(a) as unpatentable over Kozak or Gericke in view of Hemadi or
Ozguroglu as evidenced by SGO further in view of Engel.
4 Zhang et al., WO 2007/002264 A2, published Jan. 4, 2007 (“Zhang”).
5 Soc. Gyn. Oncol., What is a gynecologic oncologist?,
www.sgo.org/patients-caregivers-survivors/what-is-a-gynecologic-
oncologist/ (last visited Sept. 30, 2014) (“SGO”).
6 Engel et al., Moderate progress for ovarian cancer in the last 20 years:
prolongation of survival, but no improvement in the cure rate, 38 Eur. J.
Cancer 2435 (2002) (“Engel”).
7 Kozak et al., Characterization of serum biomarkers for detection of early
stage ovarian cancer, 5 Proteomics 4589 (2005) (“Kozak”).
8 Gericke et al., Microheterogeneity of transthyretin in serum and ascetic
fluid of ovarian cancer patients, 5 BMC Cancer 133 (2005) (“Gericke”).
9 Hemadi et al., The follow-up of ovarian cancer patients with Beta-2 -
Microglobin and CA-125, 114 Zent. Bl. Gynakol. 6 (1992) (“Hemadi”).
Citations are to the English translation.
10 Ozguroglu et al., Significance or Serum Beta-2 Microglobulin in
Epithelial Ovarian Cancer (Meeting Abstract) (1999),
http://www.asco.org/ascov2/Meetings/Abstracts?&vmview=abst_detail_vie
w&confID=17 (last visited June 23, 2011) (“Ozguroglu”).
3
Appeal 2016-004829
Application 12/422,530
THE REJECTION UNDER 35 U.S.C. § 101
Issue
The issue with respect to this rejection is whether a preponderance of
evidence supports the Examiner’s finding that claims are directed to patent
ineligible subject matter under 35 U.S.C. § 101.
The Examiner finds that the claims encompass a law of nature or
natural phenomenon and do not recite something significantly different in
that the additional limitations are conventional. Final Act. 3. The Examiner
finds that, applying the test outlined in the 2014 Guidance,11 the factors
weigh against finding the claims to be patentable. Final Act. 6—9.
Appellant contends that his invention recites something significantly
more than a law of nature in that methods used to measure the biomarkers
and the step of identifying a subject with a short survival time for referral to
a gynecologic oncologist are not routine or conventional. Br. 7—8.
Appellant argues that the factors recited in the 2014 Guidance weigh in
favor of finding the claims to be patentable. Br. 8—10.
11 Guidance for Determining Subject Matter Eligibility of Claims Reciting or
Involving Law of Nature, Natural Phenomena, & Natural Products, Issued
Mar. 4, 2014, www.uspto.gov/patents/law/exam/myriad-mayo_guidance.pdf
(“2014 Guidance”). The 2014 Guidance was superseded by the 2014
Interim Guidance on Patent Subject Matter Eligibility, 79 Fed Reg. 74618
(Dec. 16, 2014).
4
Appeal 2016-004829
Application 12/422,530
Analysis
As stated in In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992):
[T]he examiner bears the initial burden ... of presenting a
prima facie case of unpatentability. . . .
After evidence or argument is submitted by the applicant
in response, patentability is determined on the totality of the
record, by a preponderance of evidence with due consideration
to persuasiveness of argument.
As discussed below, we find that a preponderance of the evidence
supports the Examiner’s conclusion that the rejected claims recite subject
matter ineligible for patenting under 35 U.S.C. § 101.
35 U.S.C. § 101 states that “[wjhoever invents or discovers any new
and useful process, machine, manufacture, or composition of matter, or any
new and useful improvement thereof, may obtain a patent therefor, subject to
the conditions and requirements of this title.”
The Supreme Court has “long held that this provision contains an
important implicit exception: Laws of nature, natural phenomena, and
abstract ideas are not patentable.” Alice Corp. Pty. Ltd. v. CLS Bank Intern.,
134 S. Ct. 2347, 2354 (2014) (quoting Assoc, for Molecular Pathology v.
Myriad Genetics, Inc., 133 S. Ct. 2107, 2116 (2013)).
Our reviewing court has summarized the Supreme Court’s two-part
test for distinguishing between claims to patent-ineligible exceptions, and
claims to patent-eligible applications of those exceptions, as follows:
Step one asks whether the claim is “directed to one of
[the] patent-ineligible concepts.” [Alice, 134 S. Ct. at 2354], If
the answer is no, the inquiry is over: the claim falls within the
ambit of § 101. If the answer is yes, the inquiry moves to step
two, which asks whether, considered both individually and as
an ordered combination, “the additional elements ‘transform the
5
Appeal 2016-004829
Application 12/422,530
nature of the claim’ into a patent-eligible application.” Id.
(quoting Mayo [Collaborative Services v. Prometheus Labs,
Inc., 132 S. Ct. 1289, 1297 (2012)]).
Step two is described “as a search for an ‘inventive concept.’”
Id. (quoting Mayo, 132 S. Ct. at 1294). At step two, more is
required than “well-understood, routine, conventional activity
already engaged in by the scientific community,” which fails to
transform the claim into “significantly more than a patent upon
the” ineligible concept itself. Mayo, 132 S. Ct. at 1298, 1294.
Rapid Litigation Mgmt. Ltd. v. CellzDirect, Inc., 827 F.3d 1042, 1047 (Fed.
Cir. 2016) (paragraphing added).
In the present case, claim 1 recites the step of “correlating the
measurements with ovarian cancer patient length of survival, wherein the
expression or up-regulation of beta-2 microglobulin and the down-regulation
of transthyretin is indicative of short survival.” Br. 23 (claim 1).
We agree with the Examiner that, as to part one of the Supreme
Court’s test, Appellant’s claim 1 is expressly directed to the law of nature
discovered by Appellant—that the up-regulation of B2M and the down-
regulation of TTR in patients with ovarian cancer correlates with a short
survival.
As to part two of the Supreme Court’s test, the other steps in
Appellant’s claim 1, using either mass spectroscopy or immunoassay to
determine the concentration of TTR and B2M and identifying a subject for
referral to a gynecologic oncologist, are well understood, conventional, and
routine, as explained by the Examiner and the prior art. Final Act. 5; Zhang
1192, 108-110; SGO.
6
Appeal 2016-004829
Application 12/422,530
We, therefore, agree with the Examiner that, under the Supreme
Court’s two-part test, claim 1 recites subject matter ineligible for patenting
under § 101.
Appellant’s arguments do not persuade us to the contrary.
Appellant contends that the combination of biomarkers was not
conventionally measured by skilled artisans and that this represents an
unconventional step. Br. 7. We are not persuaded. Zhang specifically
teaches “measuring and correlating at least one biomarker selected from the
group consisting of’ TTR and B2M. Zhang 117. Hemadi, Kozak, Gericke,
and Ozguroglu all teach measuring two or more biomarkers for ovarian
cancer. We agree with the Examiner that measuring the concentration of
TTR and B2M would have been conventional. Ans. 10.
Appellant also argues that the steps in claims 1, 55, and 60, which call
for application of the findings and taking direct action, distinguishes the
present invention from the claims in Mayo and do not involve a routine or
conventional step. Br. 8. Again, we are unpersuaded. Zhang teaches:
In certain embodiments of the methods of qualifying
ovarian cancer status, the methods further comprise managing
subject treatment based on the status. Such management
includes the actions of the physician or clinician subsequent to
determining ovarian cancer status. For example, if a physician
makes a diagnosis of ovarian cancer, then a certain regime of
treatment, such as prescription or administration of therapeutic
agent, might follow.
Zhang 1110. SGO teaches that “[i]t is important to consult with a
gynecologic oncologist before treatment is started so that the best treatment
regimen is chosen for you.” SGO. We agree with the Examiner that the
7
Appeal 2016-004829
Application 12/422,530
additional steps recited in the claims would have been conventional and
routine. Ans. 10.
With respect to Appellant’s application of the factors recited in the
2014 Guidance, we find them unpersuasive for the reasons set forth by the
Examiner, which we adopt as our own. Final Act. 7—9.
In sum, for the reasons discussed, Appellant does not persuade us that
a preponderance of the evidence fails to support the Examiner’s conclusion
that Appellant’s claim 1 is patent-ineligible under § 101. Accordingly, we
affirm the Examiner’s rejection of claim 1 on that ground. Because they
were not argued separately, claims 17, 29, 31, 55, and 60 fall with claim 1.
See 37 C.F.R. § 41.37(c)(l)(iv).
THE REJECTIONS UNDER 35 U.S.C. § 103(a)
In discussing the rejections under 35 U.S.C. § 103(a) we find claim 1
to be representative of the rejected claims. Claim 1 is directed to a method
for identifying a patient for referral to a gynecologic oncologist using a
correlation of TTR and B2M levels to indicate the survival interval of the
patient.
ZHANG AS EVIDENCED BY SGO
Issue
The issue with respect to this rejection is whether a preponderance of
the evidence supports the Examiner’s finding that claim 1 would have been
obvious over Zhang as evidenced by SGO.
The Examiner finds that Zhang discloses a method for determining an
ovarian cancer patient’s prognosis by determining the level of certain
proteins including TTR and B2M using mass spectrometry (MS-SELDI-
8
Appeal 2016-004829
Application 12/422,530
based immunoassay). Final Act. 10—11. The Examiner finds that Zhang
discloses that the down regulation of TTR and up-regulation of B2M
correlates with cancer status including stage of disease in a subject which, in
turn, correlates with survival rate. Id. The Examiner goes on to find that
while Zhang does not teach selecting a patient for referral to a specialist, “it
is known that ovarian cancer is a gynecological cancer, which would be
taken care by the specialist as evidenced by online publication of SGO
(society of gynecological oncology).” Id. at 11. The Examiner concludes,
[I]t would have been prima facie obvious to one of
ordinary skill in the art at the time the claimed invention was
made to refer the ovarian patient having short survival time to a
gynecologic oncologist for treatment and care with expected
result. One of ordinary skill in the art at the time the invention
was made would have been motivated with reasonable
expectation of success to send the short survival ovarian
patients to a gynecologic oncologist because Zhang et al have
shown the levels of B2M and TTR correlate to the ovarian
cancer stage. One would arrive at current invention with step 3
of the base claims without unexpected result because ovarian
cancer is a gynecological cancer and the gynecological
oncologist is the best doctor to take care the patients.
Id.
Appellant contends that the cited references do not teach the
correlation between the makers TTR and B2M with the length of patient
survival. Br. 11—12. Appellant argues that the limitation of identifying a
patient for referral to a gynecologic oncologist is also not taught by the
references. Br. 12. Appellant argues that the Examiner improperly took
official notice of that the step of “identifying a subject having a short
survival time for referral to a gynecologic oncologist” is well known. Br
12—13. Appellant argues that referral of a patient to a gynecologic
9
Appeal 2016-004829
Application 12/422,530
oncologist is not a well-known step. Br. 13. Appellant also argues that the
Examiner has failed to explain why the differences between the invention
and the cited art would have been obvious to one skilled in the art. Id-
Findings of Fact
We adopt as our own the Examiner’s findings and analysis. The
following findings are included for emphasis and reference convenience.
FF1. Zhang teaches
a protein-based biomarker that is useful in qualifying ovarian
cancer status in a patient. In particular, the biomarker of this
invention is useful to classify a subject sample as ovarian
cancer or non-ovarian cancer. The biomarker can be detected
by SELDI mass spectrometry.
Zhang, Abstract
FF2. Zhang teaches that
the method for qualifying ovarian cancer status further
comprises measuring and correlating at least one biomarker
selected from the group consisting of CA125, transferrin,
haptoglobin, ApoAl, transthyretin, ITIH4 internal fragment,
beta 2-microglobulin, hepcidin, prostatin, osteopontin,
esoinophil-derived neurotoxin, leptin, prolactin, IGF-II,
hemoglobin and modified forms thereof with ovarian cancer
status.
Zhang 117.
FF3. Zhang discloses that the up-regulation of B2M and the down-
regulation of TTR correlate with cancer status including the stages and
progression of the disease. Zhang Table 3.
FF4. Zhang discloses that the stages of ovarian cancer correlate with
a step survival gradient and that a later stage of cancer means a lower
survival rate. Zhang || 106—107.
10
Appeal 2016-004829
Application 12/422,530
FF5. Zhang teaches:
In certain embodiments of the methods of qualifying
ovarian cancer status, the methods further comprise managing
subject treatment based on the status. Such management
includes the actions of the physician or clinician subsequent to
determining ovarian cancer status. For example, if a physician
makes a diagnosis of ovarian cancer, then a certain regime of
treatment, such as prescription or administration of therapeutic
agent, might follow.
Zhang 1110.
FF6. SGO teaches that “[i]t is important to consult with a
gynecologic oncologist before treatment is started so that the best treatment
regimen is chosen for you.” SGO
Principles of Law
“The factual predicates underlying an obviousness determination
include the scope and content of the prior art, the differences between the
prior art and the claimed invention, and the level of ordinary skill in the art.”
In reRouffet, 149 F.3d 1350, 1355 (Fed. Cir. 1998).
“[Wjhile an analysis of obviousness always depends on evidence that
supports the required Graham factual findings, it also may include recourse
to logic, judgment, and common sense available to the person of ordinary
skill that do not necessarily require explication in any reference or expert
opinion.” Perfect Web Techs., Inc. v. InfoUSA, Inc., 587 F.3d 1324, 1329
(Fed. Cir. 2009).
Analysis
We agree with the Examiner that the subject matter of claim 1 would
have been obvious to one skilled in the art at the time the invention was
11
Appeal 2016-004829
Application 12/422,530
made. Zhang teaches determining the level of the biomarkers TTR and B2M
for ovarian cancer as well as their correlation to the disease stage and
progression of the cancer. FF1 4. Zhang teaches managing treatment of a
patient by a physician or clinician. FF5. SGO teaches the importance of
consulting a gynecologic oncologist before starting treatment for a
gynecologic cancer. FF6. We agree with the Examiner that it would have
been obvious to refer a patient to a gynecologic oncologist when the patient
has levels of the biomarkers TTR and B2M recited in the claims.
Appellant contends that the references do not teach that TTR and
B2M are indicative of the patient’s length of survival. Br. 11—12. Appellant
argues that ovarian cancer survival is independent of the stage of cancer. Br.
12. We are unpersuaded. Appellant points to nothing in the record to
support the argument that length of survival is independent of cancer stage.
As the Examiner points out, one skilled in the art would understand that the
higher the stage of the cancer or quicker progressed cancer would result in
short survival time for the patient. Ans. 11. This finding is supported by
evidence of record including Appellant’s own Specification. Ans. 11; Spec.
Fig. 15 A.
Appellant contends that the Examiner improperly took official notice
of the fact that the references teach referral to a gynecologic oncologist. Br.
13. We are unpersuaded. Zhang teaches management of the treatment of
ovarian cancer by a physician or clinician. FF5. SGO teaches that a
gynecologic oncologist is the best person to lead the decision-making
process relative to treatment of gynecologic cancers. FF6. The Examiner’s
finding is a logical conclusion based on the teachings of the references.
Perfect Web Techs., 587 F.3d at 1329.
12
Appeal 2016-004829
Application 12/422,530
Appellant argues that the New York Times12 article indicating that
many patients do not receive care from a gynecologic oncologist supports
the argument that referral to such a specialist is not a well-know or common
practice. Br. 13. We remain unpersuaded. The test for obviousness is what
the combined teachings of the references as a whole would have suggested
to those of ordinary skill in the art. In re Keller, 642 F.2d 413, 425 (CCPA
1981). The references teach one skilled in the art to refer a patient with
ovarian cancer who has a short life expectancy to a gynecologic oncologist.
See, FF5 and 6.
Appellant argues that the Examiner has failed to explain the rationale
for combining the references. We do not agree. The Examiner has shown
that Zhang teaches all of the elements of claim 1 with the exception of the
specific limitation regarding referral to a gynecological oncologist. Ans.
11—12. SGO teaches the importance of having a gynecological oncologist
coordinate the treatment of a patient with a gynecologic cancer, such as
ovarian cancer. FF6. As the Examiner points out, a gynecologic oncologist
is the specialist a patient with ovarian cancer is most likely to see for
treatment. Ans. 12.
Conclusion of Law
We conclude that a preponderance of the evidence supports the
Examiner’s finding that claim 1 would have been obvious over Zhang as
evidenced by SGO.
12 Denise Grady, Widespread Flaws Found in Ovarian Cancer Treatment,
N.Y. Times, Mar. 11,2013.
13
Appeal 2016-004829
Application 12/422,530
Claims 29, 31, 55, and 60 have not been argued separately and
therefore fall with claim 1. 37 C.F.R. § 41.37(c)(l)(iv).
ZHANG COMBINED WITH ENGEL AND EVIDENCED BY SGO
Issue
The issue with respect to this rejection is whether a preponderance of
the evidence supports the Examiner’s finding that claims 1, 17, 29, 31, 55,
and 60 would have been obvious over Zhang combined with Engel as
evidenced by SGO.
The Examiner’s findings with respect to Zhang are discussed above.
The Examiner notes that Zhang does not teach survival by years post
diagnosis. Final Act. 12. The Examiner finds that Engel teaches ovarian
cancer status of survival and correlates stage of cancer with survival time
with or without treatment. Id. The Examiner concludes:
It would have been prima facie obvious to one of
ordinary skill in the art at the time the claimed invention was
made to combine the methods to predict the progress of an
ovarian cancer and survival time based on the stage of the
cancer and send the patients with poor prognosis (short survival
time at high stage of the cancer) to gynecologic oncologists
with expected results. One of ordinary skill in the art at the
time the invention was made would have been motivated to
document the patients information including levels of
biomarkers in the samples, the ages, and stage of the cancer of
said patients in order to give better view or predicting for
cancer prognosis and survival time and further evaluate and get
treatment by gynecologic oncologists. One skilled in the art
would do so with reasonable expectation of success because
Zhang et al have shown the levels of biomarkers associated
with the cancer stage and Engel et al teach that a statistical
method of survival status of the patients based on the age of the
patient and stage of the cancer. Therefore, the references in
combination teach each and every limitation of the claims and
14
Appeal 2016-004829
Application 12/422,530
the invention as a whole would have been prima facie obvious
to one of ordinary skill in the art at the time the invention was
made, absent unexpected results.
Final Act. 12—13.
Appellant contends that one skilled in the art would not have a
reasonable expectation of success in combining Engel with Zhang as Engel
does not teach a clear correlation between a patient’s length of survival and
the stage of ovarian cancer. Br. 15. Appellant also argues that the
references fail to teach the limitations regarding correlation of the levels of
TTR and B2M with length of survival and identifying a patient for referral to
a gynecologic oncologist. Id-
Findings of Fact
FF7. Figure 1 of Engel reproduced below shows overall survival
differentiated by FIGO-stage (cancer stage). Engel 2437.
Fig. L Overall survival according 1o FTGO-sIngc.
PIGO
\ a (0=4-11 19.6%)
:b {rtsiBB 4.2%)
:c irivai0 9.8%)
:ia [n=70 3-3%)
Ifc {0=133 0.3%)
]]C tn.~m 4,6%)
Ilia (n=$02A%)
ilib
Hto (.0^11 24.3%)
N (n=4m ?.1.9%)
Engel 2440, Figure 1.
15
Appeal 2016-004829
Application 12/422,530
Analysis
We agree with the Examiner’s finding that claim 1 would have been
obvious to one skilled in the art at the time the invention was made. Engel
provides a correlation of cancer stage with expected survival in years. FF7.
We agree with the Examiner that the combination of references teach all of
the limitations of the claims.
Appellant contends that the survival rates in Engel are dependent on a
number of factors, not just the stage of the cancer. We are not persuaded.
Engel specifically states that the data in Figure 1 is for survival
differentiated based on cancer stage. FF7. We agree with the Examiner that
Engel teaches a correlation between cancer stage and survival length. Final
Act. 13.
Conclusion of Law
We conclude that a preponderance of the evidence supports the
Examiner’s finding that claim 1 would have been obvious over Zhang
combined with Engel as evidenced by SGO.
Claims 17, 29, 31, 55, and 60 have not been argued separately and
therefore fall with claim 1. 37 C.F.R. § 41.37(c)(l)(iv).
KOZAK OR GERICKE COMBINED WITH HERNADI OR
OZGUROGLU AS EVIDENCED BY SGO
Issue
The issue with respect to this rejection is whether a preponderance of
the evidence supports the Examiner’s finding that claim 1 would have been
obvious over Kozak or Gericke combined with Hemadi or Ozguroglu as
evidenced by SGO.
16
Appeal 2016-004829
Application 12/422,530
The Examiner finds that Kozak and Gericke teach that patients with
ovarian cancer have lower levels of TTR compared to normal and teaches
that the level of TTR is related to the stage of the cancer. Final Act. 13. The
Examiner finds that both Kozak and Gericke teach the use of SELDI-MS to
determine the level of TTR. Final Act. 13—14.
The Examiner finds that Hemadi teaches a method for determining the
prognosis of ovarian cancer patients by detecting the levels of biomarkers
including B2M. Final Act. 14. The Examiner finds that Ozguroglu also
teaches determining the prognosis of ovarian cancer patients by detecting the
levels of biomarkers including B2M. Id. The Examiner finds that
Ozguroglu teaches a correlation of up-regulation of B2M with
advanced-stage ovarian cancer, which represents a lower probability of the
patient surviving ovarian cancer. Id. While the Examiner notes that neither
Hemadi nor Ozguroglu teaches referring a patient to a gynecologic
oncologist, one skilled in the art would arrive at the current invention
“because ovarian cancer is a gynecological cancer, [a] gynecological
oncologist is best doctor to take care [of] the patients as evidenced by [the]
publication of SGO.” Final Act. 14—15.
The Examiner concludes:
It is prima facie obvious to combine two compositions
each of which is taught by the prior art to be useful for the same
purpose, in order to form a third composition to be used for the
very same purpose. The idea of combining them flows
logically from their having been individually taught in the prior
art.[] SEE In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ
1069, 1072 (CCPA 1980) and MPEP 2144.06. One of ordinary
skill in the art would have been motivated with a reasonable
expectation of success to combine the two biomarkers of TTR
and B2M in order to increase the accuracy of prognosing
17
Appeal 2016-004829
Application 12/422,530
ovarian cancer and then send the patients to Gynecologic
Oncologist because the references teach two biomarkers, up-
regulated of B2M and down regulated of TTR in the serum of
ovarian cancer patients, which are correlated with the prognosis
and survival of the cancer and then the patients would be
treated by a Gynecologic Oncologist as evidenced by SGO
publication.
Final Act. 15.
Appellant contends that none of the references teach or suggest that
TTR and B2M, either alone or in combination, is indicative of how long an
ovarian cancer patient will survive. Br. 16. Appellant argues that length of
survival is independent of cancer stage. Id. Appellant argues that Gericke
does not teach a correlation between the level of TTR and the stage of
cancer, rather Gericke teaches that TTR level is independent of cancer stage.
Br. 17. Appellant contends that Kozak does not teach a correlation between
TTR level and length of survival. Id. Appellant goes on to argue that there
is nothing in the references to teach or suggest combining the references.
Br. 18. Appellant argues that there is nothing in the record to support the
Examiner’s position that increasing the number of biomarkers would
increase the accuracy of prognosing cancer. Id.
Findings of Fact
FF8. Kozak teaches the detection of TTR and other biomarkers in
patients with ovarian cancer using mass spectrometry. Kozak 4589
Abstract.
FF9. Kozak teaches that “[t]he 5-year survival for patients with early
stage disease ranges from 50—95%, but it is less than 25% for
advanced-stage disease.” Kozak 4589.
18
Appeal 2016-004829
Application 12/422,530
FF10. Kozak teaches “[mjultivariate analysis of these markers, in
combination with CA125, resulted in improved detection of early stage
ovarian cancer.” Kozak 4590.
FF11. Kozak discloses:
Using specific antibodies, we further confirmed the differential
expression of TTR, Hb, and TF in serum samples from normal
individuals, and patients with early stage (I/II) or late stage
(Ill/IV) ovarian cancer by Western blotting. Membranes probed
with anti-TTR or anti-sero-TF showed a decrease in protein
levels (Fig. 4), while anti-Hb antibody showed an increase in
expression between nolmal, early and late stage ovarian cancer
(Fig. 4).
]5t[4kDa
7:&VQij
Figure 4, TTR, Hb.,- and TF differentially expressed In serum from
ovarian cancer patients as determined by Western analysis. Total
serum protein was determined by Bradford assay (Sigma-Aldrichl
using BSA standards and equal protein concentrations were
loaded onto SDS-FAGB for TTR, Hb and TF. For the TTR Western,
1 jjg total serum protein was resolved on a 15% get TTR primary
antibody was used at a 1:1000 dilution and the secondary anti-
rabbit HRP at 1;4QQ0, FortbeHbWestern, 30 pg total serum protein
was resolved on a 15% gel Hb primary antibody was used at a
1:1000 dilution and the secondary anti-goat HRP at 1:4000. For the
TF Western, 0,1 jig total serum protein was resolved on s 4-16%
gradient gei, TF primary antibody was- used at a 1:2000 dilution
and secondary anti-rabbit HRP at 1:4600. Molecular weight
protein markers correlating to each gsi are Indicated,
Kozak 4592-93.
FF12. Gericke teaches measuring levels of TTR in patients with
ovarian cancer using mass spectrometry. Gericke 1, Abstract.
19
Appeal 2016-004829
Application 12/422,530
FF13. Gericke teaches that the “mean levels of TTR and RBP in
serum showed a tendency to decrease with the severity of the disease.”
Gericke 1, Abstract, 4, Table 1.
FF14. Gericke teaches that “[t]umor stage is one of the most
important prognostic factors in ovarian cancer. The 5-year survival rate for
FIGO stage III ranges from 25 to 45%, whilst for patients diagnosed at
FIGO stage I or II, survival rates are between 85 and 95%.” Gericke 2
(citations omitted).
FF15. Hemadi teaches the use of B2M as a biomarker for ovarian
cancer. Hemadi 2, Abstract.
FF16. Hemadi teaches that secretion of B2M by cancer cells is higher
than normal cells and “seems to be related to the stage and course of the
disease.” Hemadi 2—3.
FF17. Hemadi teaches that the combination of biomarkers C125 and
B2M is a reliable method of biochemical monitoring of ovarian carcinoma.
Id.
FF18. Hemadi teaches that biomarkers can be used for predicting
cancer prognosis and that the higher stage indicates lower survival. Hemadi
5, Table 1.
FF19. Ozguroglu teaches the measurement of B2M in patients with
ovarian cancer and that the level of B2M increase with the stage of cancer.
Ozguroglu Abstract.
Analysis
We agree with the Examiner that the subject matter of claim 1 would
have been obvious to one skilled in the art at the time the invention was
made. Kozak and Gericke both teach the correlation of lower TTR levels
20
Appeal 2016-004829
Application 12/422,530
with higher stages of cancer. FF11 and 13. Hemadi and Ozguroglu teach
that increased levels of B2M correlated with later stages of cancer. FF16
and 19. Kozak, Hemadi, and Ozguroglu teach that the use of two or more
biomarkers increases the accuracy of the assay. FF10, 17, and 18. Kozak,
Gericke, and Hemadi teach the correlation between cancer stage and length
of survival. FF9, 14, and 18. SGO teaches the importance of seeing a
gynecologic oncologist to ensure that the best treatment regimen is chosen.
FF6. We agree with the Examiner that the present invention would have
been obvious over Kozak or Gericke combined with Hemadi or Ozguroglu
as evidenced by SGO. Final Act. 15.
Appellant contends that length of survival is independent of cancer
stage. Br. 16. As discussed above, Appellant offers no support for this
statement. Moreover, Kozak, Gericke, and Hemadi all teach that there is a
correlation between cancer stage and length of survival. FF9, 14, 18.
Appellant argues that Gericke teaches that there is no correlation
between TTR levels and the stage of cancer. Br. 17. We are unpersuaded.
As the Examiner points out, Gericke specifically teaches that levels of TTR
decrease with the severity of the disease. Ans. 14; FF13.
Appellant contends that Kozak does not teach that TTR levels is a
significant maker in late stage cancer. Br. 17. We agree with the Examiner
that Kozak teaches that a patient has different levels of TTR depending on
the stage of cancer and that a low level of TTR is indicative of later stage
cancer. Ans. 14;FF11.
Appellant contends that Hemadi and Ozguroglu teach using B2M
with biomarkers other than TTR and that the references teach that simply
increasing the number of biomarkers does not necessarily increase the
21
Appeal 2016-004829
Application 12/422,530
accuracy of the prognostication. Br. 18. We remain unpersuaded. Hemadi
and Ozguroglu teach that up-regulation of B2M is associated with late stage
cancer. FF16 and 19. As the Examiner points out, the present claims do not
exclude the presence of other biomarkers. Ans. 15. Kozak and Hemadi
teach that using more than one biomarker results in improved levels of
detection. FF10 and 17. The teachings that two or more biomarkers
increases detection would motivate one skilled in the art to combine the
teachings of the references.
Conclusion of Law
We conclude that a preponderance of the evidence supports the
Examiner’s finding that claim 1 would have been obvious over Kozak or
Gericke combined with Hemadi or Ozguroglu and evidenced by SGO.
Claims 29, 31, 55, and 60 have not been argued separately and
therefore fall with claim 1. 37 C.F.R. § 41.37(c)(l)(iv).
KOZAK OR GERICKE COMBINED WITH HERNADI OR
OZGUROGLU AND ENGEL AS EVIDENCED BY SGO
The arguments and evidence presented by the Examiner and
Appellant are the same as discussed above. Br. 20; Ans. 15—16. For the
reasons stated above, we affirm this rejection.
SUMMARY
We affirm the rejection based on35U.S.C. § 101.
We affirm the rejections based on 35 U.S.C. § 103(a).
22
Appeal 2016-004829
Application 12/422,530
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
23