Ex Parte Baker et al

Patent Trial and Appeal Board

Dec 1, 2016

12950732 (P.T.A.B. Dec. 1, 2016)

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.
12/950,732 11/19/2010 Joffre B. BAKER GHI-040/US 8330
80811 7590 12/05/2016
Genomic Health, Inc. / McNeill Baur PLLC
301 Penobscot Road
Redwood City, CA 94063
EXAMINER
BROWN, MINDY G
ART UNIT PAPER NUMBER
1636
NOTIFICATION DATE DELIVERY MODE
12/05/2016 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):
genomic_docketing@cardinal-ip.com
docketing @ mcneillbaur. com
eofficeaction @ appcoll.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte JOFFRE B. BAKER, MAUREEN T. CRONIN,
FRANCOIS COLLIN and MEI-LAN LIU1
Appeal 2015-002690
Application 12/950,732
Technology Center 1600
Before JEFFREY N. FREDMAN, JOHN G. NEW
and TIMOTHY G. MAJORS, Administrative Patent Judges.
MAJORS, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to methods
of predicting cancer recurrence, which have been rejected as being directed
to non-statutory subject matter and nonenabled. We have jurisdiction under
35 U.S.C. § 6(b).
We affirm.
1 Appellants identify the Real Party in Interest as Genomic Health, Inc.
(App. Br. 3.)
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STATEMENT OF THE CASE
Appellants’ “invention provides a set of genes, the expression levels
of which are associated with a particular clinical outcome in cancer.” (Spec.
^ 7.) According to the Specification, “the clinical outcome could be a good
or bad prognosis assuming the patient receives the standard of care. The
clinical outcome may be defined by clinical endpoints, such as disease or
recurrence free survival, metastasis free survival, overall survival, etc.” (Id.)
The Specification further discloses
the present invention concerns a method of predicting a clinical
outcome of a cancer patient, comprising (a) obtaining an
expression level of an expression product (e.g., an RNA
transcript) of at least one prognostic gene [such as IL6ST]... (b)
normalizing the expression level of the expression product of the
at least one prognostic gene . . . and (c) calculating a risk score
based on the normalized expression value, wherein increased
expression of prognostic genes ... are positively correlated with
good prognosis.
(Id. at 9.)
Claims 1, 6, 19-22, 24, 26, and 28-30 are on appeal. Claim 1 is
illustrative:
1. A method predicting whether a human patient diagnosed
with breast cancer has an increased or decreased likelihood of
cancer recurrence comprising:
(a) quantitatively measuring a level of an mRNA
transcript of IL6ST in a fixed, paraffin-embedded tissue sample
obtained from a tumor of the patient;
(b) normalizing the level of the mRNA transcript of
IL6ST against one or more reference mRNA transcripts in the
sample to obtain a normalized IL6ST expression level;
(c) using a computer implemented program to compare
the normalized IL6ST expression level to a statistical model-
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predicted relationship between normalized IL6ST expression
level and likelihood of cancer recurrence determined from a
population of patients with breast cancer and with known clinical
outcome; and
(d) generating a report comprising a prediction whether
the patient has an increased or decreased likelihood of cancer
recurrence.
(App. Br. 33 (Claims App’x).)
The claims stand rejected as follows:
Claims 1, 6, 19-22, 24, 26, and 28-30 under 35 U.S.C. § 101 as
directed to non-statutory subject matter.
Claims 1, 6, 19-22, 24, 26, and 28-30 under 35 U.S.C. § 112, first
paragraph, as failing to comply with the enablement requirement.
DISCUSSION
Patentable Subject Matter — 35 U.S.C. ft101
In analyzing patent eligibility under 35 U.S.C. § 101, the Supreme
Court has set forth a “framework for distinguishing patents that claim
[patent-ineligible] laws of nature, natural phenomena, and abstract ideas
from those that claim patent-eligible applications of those concepts.” Alice
Corp. Pty. Ltd. v. CLSBanklnt’l, 134 S. Ct. 2347, 2354 (2014). According
to that framework, first “we determine whether the claims at issue are
directed to one of those patent-ineligible concepts.” Id. at 2355. “If so, we
then ask, ‘[w]hat else is there in the claims before us?’” Id. (quoting Mayo
Collaborative Servs. v. Prometheus Labs., Inc., 132 S. Ct. 1289, 1297
(2012).) To answer this second question,
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we consider the elements of each claim both individually and as
an ordered combination to determine whether the additional
elements transform the nature of the claim into a patent-eligible
application. [The Supreme Court has] described step two of
this analysis as a search for an inventive concept — i.e., an
element or combination of elements that is sufficient to ensure
that the patent in practice amounts to significantly more than a
patent upon the [ineligible concept] itself.
Id. (internal citations and quotation marks omitted).
Appellants argue the patentability of the claims as a group. We select
claim 1 as representative. 37 C.F.R. § 41.37(c)(l)(iv).
The Examiner rejected claim 1, finding that the claim is directed to a
patent-ineligible law of nature. (Ans. 2.) According to the Examiner, “[t]he
claims are drawn to a method for determining a likelihood of cancer
recurrence of a human patient diagnosed with breast cancer” yet “[t]he
correlation between the expression level of an RNA transcript and the
patient’s likelihood of cancer recurrence is considered a Taw of nature’ in
accordance with Mayo Collaborative Services v. Prometheus Laboratories,
Inc.” (Id.; see also id. at 12-15; see also Final Act. 3.)
The Examiner finds that “[t]he additional steps of measuring,
normalizing, applying a statistical method, and generating a report are well
understood steps that are routinely conducted to analyze an mRNA transcript
. . . [and are] claimed at a high level of generality.” (Final Act. 3; see also
Ans. 3—4.) As the Examiner explains, “[a] claim that recites a law of nature
or natural correlation, with additional steps that involve well-understood,
routine, conventional activity previously engaged in by researchers in the
field is not patent-eligible.” (Ans. 4.) Thus, according to the Examiner,
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“considered as a whole, the steps taken together amount to no more than
recognizing the law of nature itself.” (Final Act. 3.)
We agree with, and adopt, the Examiner’s findings and conclusion
that claim 1 is ineligible for patenting under § 101. (Ans. 2-5 and 12-15;
Final Act. 2-3.) Analyzing claim 1 according to the Alice/Mayo framework,
we agree with the Examiner that claim 1 is directed to a law of nature or
natural phenomenon that is a correlation or association between an
expression product (mRNA of IL6ST) and cancer risk. With respect to the
claim elements individually and as an ordered combination — step two of
the Alice/Mayo framework — the Examiner finds the steps of measuring,
normalizing, comparing, and generating a report are conventional and
routine steps previously engaged in by those in the field. See Mayo, 132
S.Ct. at 1298 (“well-understood, routine, conventional activity previously
engaged in by scientists who work in the field ... is normally not sufficient
to transform an unpatentable law of nature into a patent-eligible application
of such law.”) Appellants have not persuasively shown otherwise.
We address below Appellants’ arguments.
Appellants argue “the instant claims are not directed to a natural
phenomenon . . . [and instead] recite a statistical model-predicted
relationship between normalized IL6ST expression level or a normalized
IL6ST amplicon level and likelihood of cancer recurrence.'''’ (App. Br. 8.)
As such, Appellants contend, the claims are “NOT a product of nature, but []
rather a product of human ingenuity and human intervention.” (Id. at 9.)
This argument is unpersuasive. At its core, claim 1 is drawn to a
natural phenomenon or law of nature — the correlation between expression
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levels of an mRNA of IL6ST and a risk of cancer recurrence. We are not
persuaded that the recitation of a statistical model does significantly more
than exploit and inform a relevant audience about the correlation itself. See
Mayo, 132 S. Ct. at 1297 (“The process that each claim recites tells doctors
interested in the subject about the correlations that the researchers
discovered.”); Digitech Image Techs. LLC v. Elecs. For Imaging, Inc., 758
F.3d 1344, 1351 (Fed. Cir. 2014) (“Without additional limitations, a process
that employs mathematical algorithms to manipulate existing information to
generate additional information is not patent eligible.”)
Appellants further argue “prediction of the likelihood of an outcome
using a statistical model is not a natural phenomenon” and instead “takes
human action and human ingenuity to make such a prediction.” (App. Br.
9.) This argument fails to persuade us that claim 1 is drawn to patent-
eligible subject matter. On this point, we turn to the Supreme Court’s
guidance in Mayo. The claims in Mayo recited a “method of optimizing
therapeutic efficacy for treatment” requiring, inter alia, “administering” and
“determining” steps that “take[] human action” and were “not themselves
natural laws.” Mayo, 132 S.Ct. at 1295, 1297. The claims further required
that the outcome of the “determining” step would indicate [to the doctor] a
need to either increase or decrease the amount of drug administered to a
patient. Id. Notwithstanding these claim elements requiring human
intervention, the Court held that the claims were drawn to patent-ineligible
“laws of nature—namely, relationships between concentrations of certain
metabolites in the blood and the likelihood that a dosage of thiopurine drug
will prove ineffective or cause harm.” Id. at 1296.
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Claim 1 is analogous to the patent-ineligible claims in Mayo.
Although the “statistical model” and “prediction” recited in Appellants’
claim 1 may involve human (or computer) intervention, we are not
persuaded those elements transform claim 1 into a patentable application of
the natural law or phenomenon.2 Id. at 1295-96; see also Alice, 134 S. Ct.
2358 (“the mere recitation of a generic computer cannot transform a patent-
ineligible abstract idea into a patent-eligible invention.”)
Appellants further argue that, even if the claims recite a law of nature
or natural phenomenon, the claims as a whole recite something
“significantly different.” (App. Br. 9.) In this respect, Appellants contend
claim 1 is meaningfully limited, and thus does not foreclose others from
using the natural phenomenon, because the claims relate to a single type of
cancer, analyte, gene, and sample type. {Id. at 10-11.) Appellants further
contend “the pending claims do not claim a known, proven, direct
mechanistic connection between a biological marker and a particular
disease” but rather “a statistical correlation between one or more
physiochemical characteristics of specific biomarkers and the underlying
disease.” {Id. at 11.) In other words, Appellants argue, “the pending claims
2 The Examiner found that “Applicant has not recited [in claim 1] a specific
statistical model.” (Final Act. 3.) Appellants acknowledge as much, but
contend “one of ordinary skill in the art reading the claims in light of the
specification would understand the statistical methods encompassed,” and
Appellants cite paragraph 133 of the Specification as an example. (App. Br.
8.) Claim 1 broadly recites “a statistical model-predicted relationship” and
we decline to read limitations from the example cited by Appellants into the
claims. In re Bigio, 381 F.3d 1320, 1325 (Fed. Cir. 2004).
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are drawn to a clinically useful statistical approximation of a biological
reality identified by scientists, not simply to a law of nature.” (Id.)
These arguments are unpersuasive. With respect to Appellants’
contention that the claims do not foreclose all uses of a natural phenomenon,
the Federal Circuit’s analysis in Ariosa is instructive. Ariosa Diagnostics,
Inc. v. Sequenom, Inc., 788 F.3d 1371 (2015), cert, denied 579 U.S.__
(2016). In Ariosa, Appellants argued “the particular application of the
natural phenomena that the [] patent claims embody are narrow and specific”
and thus did not “preclude alternative methods [of using cffDNA] in the
same field.” Ariosa, 788 F.3d at 1378. The Federal Circuit nevertheless
held that “the absence of complete preemption does not demonstrate patent
eligibility” and noted that “[t]he Supreme Court cases [] have not
distinguished among different laws of nature or natural phenomenon
according to whether or not the principles they embody are sufficiently
narrow.” Id. at 1379. The Federal Circuit further held that “[wjhere a
patent’s claims are deemed only to disclose patent ineligible subject matter
under the Mayo framework, . . . preemption concerns are fully addressed and
made moot.” Id.
Appellants’ argument here that the claims are narrow and not wholly
preemptive fares no better than the similar, but unsuccessful, argument in
Ariosa. As noted above, under the Alice/Mayo framework, Appellants’
claims are drawn to a patent ineligible natural phenomenon, and Appellants
have not persuasively shown that the Examiner erred in finding the claim
elements, individually and in combination, are conventional steps previously
employed by skilled persons that do not impart an inventive concept. (Ans.
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2-5; See, e.g., Spec. TJ 64 (“The present disclosure provides methods that
employ, unless otherwise indicated, conventional techniques of molecular
biology (including recombinant techniques), microbiology, cell biology, and
biochemistry, which are within the skill of the art. Such techniques are
explained fully in the literature.”) Appellants’ argument concerning
preempting or foreclosing others from access to the claimed natural
phenomenon or law of nature is thus unpersuasive.
Appellants’ contention that they are claiming a “statistical correlation”
and not “a known, proven, direct mechanistic connection” between mRNA
expression levels and risk of breast cancer recurrence also fails to persuade
us that claim 1 is patentable under § 101. According to Appellants, “as any
statistician will tell you, ‘correlation does not imply causation.’” (App. Br.
11.) Yet, whether Appellants discovered a cause or a correlation between
expression levels and cancer risk, the discovery remains drawn to a patent-
ineligible natural phenomenon or law of nature, just as the natural laws at
issue in Mayo were “correlations between metabolite levels and likely harm
or ineffectiveness.” Mayo, 132 S. Ct. at 1295 (emphasis added). We are
also unpersuaded on the present record that reducing a naturally-occurring
correlation to a statistical model, or expressing as a statistical relationship,
provides a sufficient inventive concept. Cf. Alice, 134 S. Ct. 2356-57 (“One
of the claims in Bilski reduced hedging to a mathematical formula, but the
Court in did not assign any special significance to that fact, much less the
sort of talismanic significance petitioner claims.”); see also Digitech, 758
F.3d at 1351.
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Inasmuch as Appellants also address the § 101 rejection based on the
2014 Procedure for Subject Matter Eligibility Analysis of Claims Reciting or
Involving Laws of Nature/Natural Principles, Natural Phenomena and/or
Natural Products (“the 2014 Guidance”) (see, e.g., App. Br. 12-14; Reply
Br. 2-7), the 2014 Guidance is encompassed by analysis under the
Alice/Mayo framework. And, for the reasons discussed above, Appellants’
arguments concerning the patentability of claim 1 under the 2014 Guidance
are unpersuasive.
We conclude the preponderance of the evidence supports the
Examiner’s determination that claim 1 is unpatentable under 35 U.S.C.
§101. Claims 6, 19-22, 24, 26, and 28-30 were not argued separately and
thus fall with claim 1.
Enablement — 35 U.S.C. ft112, First Paragraph
The Examiner rejected claims 1, 6, 19-22, 24, 26, and 28-30 under 35
U.S.C. § 112, first paragraph, as failing to comply with the enablement
requirement. The issue with respect to this rejection is: has the Examiner
established by a preponderance of the evidence that the Specification does
not enable the claimed invention?
Principles of Law
When rejecting a claim under the enablement requirement
of section 112, the PTO bears an initial burden of setting forth a
reasonable explanation as to why it believes that the scope of
protection provided by that claim is not adequately enabled by
the description of the invention provided in the specification of
the application.
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In re Wright, 999 F.2d 1557, 1561-62 (Fed. Cir. 1993). “[T]o be enabling, the
specification of a patent must teach those skilled in the art how to make and use the
full scope of the claimed invention without ‘undue experimentation.’” Id. at 1561.
Factors to be considered in determining whether a disclosure
would require undue experimentation ... include (1) the quantity
of experimentation necessary, (2) the amount of direction or
guidance presented, (3) the presence or absence of working
examples, (4) the nature of the invention, (5) the state of the prior
art, (6) the relative skill of those in the art, (7) the predictability
or unpredictability of the art, and (8) the breadth of the claims.
In re Wands, 858 F.2d 731, 737 (Fed. Cir. 1988).
Findings of Fact/Wands Factors
Breadth of Claims and Nature of the Invention
1. The Examiner finds “[t]he claims are broadly drawn to a method
for determining a likelihood of cancer recurrence of a human patient
diagnosed with breast cancer.” (Ans. 6.) The Examiner further finds that
specific “aspects considered broad are: (i) the use of an RNA transcript of
IL6ST, and (ii) the range of level of increase of the RNA transcript or
expression product thereof.” {Id. at 7-8.)
2. The Examiner finds “the nature of [Appellants’] invention is within
the broad genera of using a gene expression level to predict breast cancer
patient prognosis.” (Ans. 7.)
Predictability and State of the Art
3. The Examiner finds that “[w]ith respect to the correlation between
an[] increased level of an RNA transcript of IL6ST and a ‘good prognosis’,
the art teaches that an increased level of an RNA transcript of IL6ST is
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associated with invasive, metastatic breast tumors indicative of a poor
prognosis.” (Ans. 8 (citing Garcia-Tunon3).) According to the Examiner,
from the nature of the invention and the state of the art, the
Artisan would not reasonably predict that the increase of RNA
transcript level of IL6ST would be indicative of a reduced cancer
recurrence, as broadly claimed by the rejected claims, and in fact
the prior art teaches the increased level of an RNA transcript of
IL6ST is indicative of a “poor prognosis.”
(Ans. 9.)
4. Garcia-Tunon discloses “[i]n invasive breast tumours, the
percentage of cases showing immunoreactivity for IL-6, gpl30 and IL-6Ra
was much higher (from 74.0% to 92% of cases) than in non-malignant
lesions (23.0-53.8%), and the intensity of expression was two to three times
higher.” (Garcia-Tunon 87.) The Examiner thus finds that Garcia-Tunon
“teach a gpl30 (gpl30 is another name for IL6ST) expression level increase
of 74-92% in invasive breast tumors . . . [and] describe[s] only a weak
expression of gpl30 is observed in benign lesions.” (Ans. 8.)
5. The Examiner finds that “Crichton [] observed that the IL-6
receptor (IL6ST) was not observed in tissue surrounding a tumor, was only
observed in the tumor tissue, and that IL-6 and the IL-6 receptor promote
tumor progression.” (Ans. 8 (citing Crichton4).) According to the
3 Garcia-Tunon et al., IL-6, its receptors and its relationship with bcl-2 and
bax proteins in infdtrating an in situ human breast carcinoma, 47
Histopathology 82-89 (2005).
4 Crichton et al., Expression of transcripts of interleukin-6 and related
cytokines by human breast tumors, breast cancer cells, and adipose stromal
cells, 118 Molecular and Cellular Endocrinology 215-220 (1996).
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Examiner, “[a]s evidenced by Karczewska . . . IL-6 is known to be a
promoting or inhibitory factor in various types of tumors (page 2062) further
demonstrating the unpredictability of making any prognosis by examining
the levels of components of this [gpl30 signaling] pathway.” (Ans. 17-18
(citing Karczewska5).)
6. The Examiner finds that “Gao et al. detected a reduction of IL-6 by
RNA interference leading to a decrease in tumorgenesis . . . [and] further
stat[ed] that IL-6 leads to activation of the gpl30 signaling pathway.” (Ans.
8 (citing Gao6).) Thus, the Examiner finds, “when the IL-6 expression is
decreased it does not activate the gpl30 signaling pathway and tumorgenesis
is decreased. The prior art indicates that the activation of the IL-6/gpl30
pathway leads to an increase in tumorgenesis.” {Id. at 9)
7. The Examiner finds that, “[b]ecause the claims encompass
detecting any level... of gene expression in a sample from an individual. . .
it is relevant to point out the unpredictability associated with gene
expression in any individual.” (Ans. 9.) Also, the Examiner finds “the
claims broadly encompass determining that an RNA transcript level is
‘increased’, with no standard or references with regard to what would be
considered, for example, a normal level.” {Id. (citing Cheung7).)
5 Karczewska et al., Expression of Interleukin-6, Interleukin-6 Receptor, and
Glycoprotein 130 Correlates with Good Prognoses for Patients with Breast
Carcinoma, 88:9 Cancer 2061-2071 (2000).
6 Gao et al., Mutations in the EGFR kinase domain mediate STAT3
activation via IL-6 production in human lung adenocarcinomas, 117:12
Journal of Clinical Investigation 3846-3856 (2007).
7 Cheung et al., Natural variation in human gene expression assessed in
lymphoblastoid cells, 33 Nature Genetics 422^125 (2003).
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Amount of Direction/Guidance and Presence of Working Examples
8. The Specification discloses examples including “a study [] of
breast cancer tumor samples obtained from 136 patients with breast cancer
(‘Providence study’)” and an example involving “samples obtained from 78
evaluable cases from a Phase 11 breast cancer study conducted at Rush
University Medical Center” (“Rush study”). (Spec. 130-132 and 134—
135.)
9. The Examiner finds that Appellants’ Specification provides only
“generic guidance” with respect to the examples. (Ans. 9-10.) For instance,
the Examiner finds the Specification provides “a general reference to an
increase or decrease in RNA transcript after normalization” and “a reference
to a correlation between an increased RNA transcript level and a ‘good
prognosis’ . . . .” (Id. at 10.) The Examiner further finds that
[wjhile “prognosis” is defined [0024] and “good prognosis
. . . may be an expectation of no recurrences or metastasis” the
working example does not provide any patient data to define
“cancer recurrence” in the invention. There is no data to suggest
a time period for cancer recurrence or any patient data for that
matter to indicate the correlation between 1L6ST expression
levels and patient outcome. ... A cancer-related event is not
defined and no patient data is provided to indicate how this term
is applied in a clinical context. Furthermore, the Providence
Study, Providence Phase 11 Study, and a phase 11 breast cancer
study are referenced without providing any information about the
patient outcome and how that outcome relates to cancer
recurrence.. . . [In] Table 1 the gene IL6ST is listed as having a
negative z score without any reference to individual patient
scores or a comparison to the patient’s outcome. Therefore, the
specification does not reasonably demonstrate that a specific
patient’s increase in RNA transcript level is predictive of a
reduction in cancer recurrence in breast cancer patients.
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(Id. at 10-11.)
Amount of Experimentation Necessary
10. The Examiner finds “a large and prohibitive amount of
experimentation [would be] required to make and use the claimed invention
in the full scope as encompassed by the claims.” (Id. at 11.) For example,
according to the Examiner, “[o]ne would have to establish that any level of
increase in IL6ST RNA transcript that will result in a negative z score, is in
fact indicative that a patient has a reduced likelihood of cancer recurrence”
and “one would have to establish what the correlation [is] between reduced
‘cancer recurrence’ and an increased level [of] IL6ST RNA transcript
through clinical trials that detail patient outcome.” (Id.)
Analysis
Appellants argue the patentability of the claims subject to the
enablement rejection as a group. We select claim 1 as representative.
Based on the findings concerning the Wands factors as noted above,
the Examiner concludes there “would be an undue amount of
experimentation required to make and use the invention” and thus claim 1 is
not enabled by the Specification. (Ans. 11; see also Ans. 6-10 and 15-21.)
Appellants argue the Examiner has not sufficiently explained why the
Examiner considers claim 1 broad. (App. Br. 17.) According to Appellants,
claim 1 is, in fact, “narrowly drawn to embodiments measuring transcript
expression levels of a single gene encoding IL6ST . . ., normalizing those
expression levels to account for variability,. . . and computer-based
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implementation of a statistical model to predict... an increased or reduced
likelihood of breast cancer recurrence.” (App. Br. 23.)
This argument is unpersuasive. We agree with the Examiner that
claim 1 is broad. (FF 1-2.) Among other things, claim 1 recites
“quantitatively measuring” and “normalizing” a level of an mRNA transcript
of IF6ST. But the claim provides no range or other limitation of the level,
nor does the claim include limitations specifying any particular level or
range that correlates to an increased or decreased likelihood of cancer
recurrence. Insofar as the correlation is embodied in the “statistical-model
predicted relationship,” that claim element is itself broadly phrased. The
Specification suggests that increased expression of an expression product of
IF6ST is positively correlated with a “good prognosis,” but claim 1 is
broader than even this expansive disclosure. (See, e.g., Spec. ^ 9.)
Moreover, although Appellants defined terms like “prognosis” and
“recurrence,” those definitions are themselves broad. (See, e.g., id. at 38
(defining recurrence as “local or distant (metastasis) recurrence of cancer.”)
Appellants contend that, contrary to the Examiner’s findings, “the art
is not unpredictable.” (App. Br. 23-29; Reply Br. 10-11) Appellants argue
the “references [cited by the Examiner] are not relevant to assessing
patentability of the claimed invention, and they do not demonstrate that the
art is not [sic] unpredictable.” (Reply Br. 11.)
More specifically, Appellants argue “Crichton does not disclose
measuring expression IL6ST . . . but only cytokines of the IL-6 family and
IL-6 receptor alpha” and thus is irrelevant to expression of IL-
6R[3/gpl 30/IL6ST. (App. Br. 24.) Appellants argue “Gao is similarly
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irrelevant” because “it discloses only measuring expression of some
components of the IL-6 signaling pathway in human lung cancer-derived
cell lines, not in breast cancers.” {Id.) Appellants contend Garcia-Tunon
does not reflect the state of the art because it was published in 2005 — more
than four years before the alleged priority date of the present application.
(App. Br. 25.) Appellants also contend Garcia-Tunon does not show that the
art is unpredictable because it measured IL6ST protein levels, not the level
of IL6ST mRNA. (Id. at 25-26.) According to Appellants, protein levels do
not necessarily correlate with RNA expression levels (id. at 26) as shown in
literature (see, e.g., id. at 27 (“one skilled in the art cannot predict whether
expression levels of a particular RNA and protein will correlate without
experimental verification”) (citing Hanash8).) Appellants argue Cheung
does not render the art unpredictable because, even if Cheung discloses
natural variation in gene expression among individuals, the claims include a
“normalizing” step “because it is necessary to account for such variability.”
(App. Br. 28.)
Although Appellants’ contentions raise questions concerning how
much weight, if any, to assign each of the references cited by the Examiner,
the preponderance of the evidence of record supports the Examiner’s
determination that the art was unpredictable. Indeed, considered together,
the references including at least Garcia-Tunon, Crichton, and Gao suggest
unpredictability existed concerning the associations between cancer and IL-6
8 Hanash et al., Operomics: Integrated genomic andproteomic profiling of
cells and tissues, 1:1 Briefings in Functional Genomics and Proteomics
10-22 (2002).
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and its receptors (including gpl30/IL6ST). (FF 3-6.) As the Examiner
noted, at least Garcia-Tunon arrives at a conclusion concerning this
association that is seemingly at odds with Appellants’ discovery. (Ans. 19.)
Appellants seek to diminish Garcia-Tunon because it examined IL6ST
protein levels not mRNA levels; we note, however, that Appellants’
Specification defines “gene product” and “expression product” as including,
for example, both mRNA and “polypeptide translation products.” (Spec.
34.) And, as the Examiner points out, Appellants have “not provided
evidence that the mRNA expression levels of IL6ST do not correspond with
protein expression.” (Ans. 20.) Appellants also question Garcia-Tunon’s
relevance because it was published four years before Appellants’ filing. But
Appellants submitted no evidence reflecting a material change in the state of
the art in the years between 2004 and 2009. Moreover, in the face of the
Examiner’s evidence of unpredictability in the art, and even assuming the
artisan is highly skilled (App. Br. 23), Appellants provided no countervailing
argument or evidence demonstrating that the art was predictable.
Regarding the amount of guidance or direction provided by the
inventors, including working examples, Appellants contend “[t]he
specification discloses that IL6ST is a prognostic gene, increased expression
of which positively correlates with good prognosis, a finding that is
supported by data disclosed in the Examples and presented in the
accompanying Tables.” (App. Br. 20-21.) In response to the Examiner’s
findings on the absence of specific data about levels of IL6ST mRNA
transcript and patient outcomes, Appellants contend “[o]ne of ordinary skill
. . . would understand that information about patient outcome is taken into
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account while performing the statistical analysis described in the Examples.”
(App. Br. 29; see also Reply Br. 12.) Appellants argue “the skilled artisan
would understand the standard time periods over which cancer recurrence or
survival is measured” and also “the specification defines the relevant terms,
including ‘long-term survival[,]’ ‘good prognosis[,]’ and ‘recurrence-free
survival[.]”’ (App. Br. 29; see also Reply Br. 12-13.)
We have considered Appellants’ arguments and the cited data from
the Specification but it does not outweigh other evidence favoring the
Examiner’s determination that the full scope of claim 1 is not enabled.9 The
detail concerning the Examples provided in the Specification is wanting: as
the Examiner noted, “Applicant has not provided patient data in regards to
clinical outcome regarding cancer recurrence” and “has provided no measure
to indicate how ‘cancer recurrence’ is measured or if it in fact was
measured.” (Ans. 17; FF 8-9.) Given the breadth of the claims, including
what constitutes a “known clinical outcome” and “an increased or decreased
likelihood of cancer occurrence,” the Examiner was reasonable in pointing
out the missing data. Appellants argue the patient outcomes are accounted
for in the statistical analysis and would be understood by skilled persons, but
do not support that argument with sufficient persuasive evidence. See In re
Geisler, 116 F.3d 1465, 1471 (Fed. Cir. 1997) (argument by counsel cannot
take the place of evidence).
9 Appellants provide no citation or persuasive argument on appeal
concerning the Mar. 15, 2013 declaration of co-inventor Mei-Lan Liu, Ph.D.
(“Liu Declaration.”) In any event, the details in the Liu Declaration are not
included in the Specification and so were not part of an enabling disclosure.
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Finally, with respect to the amount of experimentation required,
Appellants argue the Examiner essentially asserts that the skilled person
“would have to repeat the analysis” in the Specification “without providing a
shred of evidence giving any reason whatsoever to doubt the objective truth
of the disclosure.” (App. Br. 31.) We are unpersuaded. As the Examiner
explained, “to make and use the claimed invention, one of ordinary skill. . .
would necessarily need information about the outcome of the patients from
which the level of IL6ST was determined” and, because this information is
absent in the Specification, “[a] study covering an unidentified number of
years would need to be undertaken to determine a cancer recurrence in those
patients.” (Ans. 21; FF 10.)
Upon considering and weighing all the Wands factors, the
preponderance of the evidence supports the Examiner’s conclusion that
undue experimentation would be required to practice the full scope of claim
1. Claims 6, 19-22, 24, 26, and 28-30 were not argued separately and thus
fall with claim 1.
SUMMARY
We affirm the rejection of claims 1, 6, 19-22, 24, 26, and 28-30 under
35 U.S.C. § 101 as directed to non-statutory subject matter.
We also affirm the rejection of claims 1, 6, 19-22, 24, 26, and 28-30
under 35 U.S.C. § 112, first paragraph, for lack of enablement.
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TIME PERIOD FOR RESPONSE
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).
AFFIRMED
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