Ex Parte Robinson et al

Patent Trial and Appeal Board

May 23, 2017

12214670 (P.T.A.B. May. 23, 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.
12/214,670 06/20/2008 William H. Robinson STAN-528 (S06-380) 2625
77974 7590 05/25/2017
Stanford University Office of Technology Licensing
Bozicevic, Field & Francis LLP
201 REDWOOD SHORES PARKWAY
SUITE 200
REDWOOD CITY, CA 94065
EXAMINER
EWOLDT, GERALD R
ART UNIT PAPER NUMBER
1644
NOTIFICATION DATE DELIVERY MODE
05/25/2017 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):
docket@bozpat.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte WILLIAM H. ROBINSON,
MICHAEL HOLERS, and KEVIN DEANE1
Appeal 2016-003281
Application 12/214,670
Technology Center 1600
Before ULRIKE W. JENKS, JOHN E. SCHNEIDER,
and TIMOTHY G. MAJORS, Administrative Patent Judges.
MAJORS, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims to
methods of prognosis for the probability of developing rheumatoid arthritis.
The claims have been rejected for lack of adequate written description, as
indefinite, as claiming non-statutory subject matter, and as obvious. We
have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.
1 Appellants identify the Real Party in Interest as the Board of Trustees of
the Leland Stanford Junior University and the Regents of the University of
Colorado. (Br. 1.)
Appeal 2016-003281
Application 12/214,670
STATEMENT OF THE CASE
The Specification discloses that “[ajutoimmune disease occurs when a
specific adaptive immune response is mounted against self antigens. . . .
Autoimmunity may be initiated by the activation of antigen-specific T cells,
although the specific triggering mechanism remains unknown.” (Spec. 12.)
The Specification also discloses that “[rjheumatoid arthritis [RA] may be
caused by TH1 cells specific for antigens present in joints. Engagement with
this antigen triggers the T cells to release lymphokines that initiate local
inflammation within the joint.” {Id. at 13.) According to the Specification,
“[rjheumatoid arthritis is a complex disease and also involves antibodies,
often including an IgM anti-IgG autoantibody called rheumatoid factor
[RF].” {Id.)
Appellants’ invention relates to methods
for prognostic classification of individuals into subtypes with
respect to development of autoimmune disease, which subtypes
are informative of the patient’s probability of developing overt
autoimmune disease. The patterns of circulating levels of serum
autoantibodies and/or cytokines identified herein provides for a
signature pattern that can discriminate individuals who have a
high probability of developing overt autoimmune disease from
those who have a low probability of developing overt
autoimmune disease.
{Id. at 19.)
Claims 1, 4—8, and 18—22 are on appeal. Claim 1 is illustrative:
1. A method for the prognosis of an individual prior to signs
of overt autoimmune disease for the probability of development
of overt rheumatoid arthritis, the method comprising:
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determining a cytokine signature pattern for median levels
of interleukin 6 (IL-6) from a blood sample obtained from said
individual;
determining an autoantibody signature pattern for median
levels of at least 3 autoantibody specificities from a sample
obtained from said individual;
comparing said cytokine and autoantibody signature
patterns with a control signature pattern to generate a
determination of prognosis for said individual; wherein a
statistically significant match with a positive pattern for an
increase in median levels of IL-6 and an increase in median
levels of at least 3 autoantibodies for pre-disease subtype or a
statistically significant difference from a normal pattern for said
increase in median levels of IL-6 and said increase in median
levels of at least 3 autoantibodies is indicative that said individual
has an increased probability of developing overt rheumatoid
arthritis; and providing said individual with said determination
of prognosis.
(Br. 22 (Claims App’x).)
The claims stand rejected as follows:
I. Claims 1, 4—8, and 18—22 under 35 U.S.C. § 112, first
paragraph (pre-AIA), for failure to comply with the written
description requirement.
II. Claim 19 under 35 U.S.C. § 112, second paragraph (pre-AIA),
for indefmiteness. (The rejection of claim 7 as indefinite was
withdrawn; see Ans. 8.)
III. Claims 1, 4—8, and 18—22 under 35 U.S.C. § 101 for claiming
patent-ineligible subject matter.
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IV. Claims 1, 4, and 6—8 under 35 U.S.C. § 103(a) over
Mangialaio2 and Rantapaa-Dahlqvist.3
V. Claims 5,19, and 20 under 35 U.S.C. § 103(a) over Mangialaio,
Rantapaa-Dahlqvist, Nielen,4 and Hitchon.5
I - WRITTEN DESCRIPTION
“In order to satisfy the written description requirement, the disclosure
as originally filed does not have to provide in haec verba support for the
claimed subject matter at issue.” Purdue Pharma L.P. v. Faulding, Inc., 230
F.3d 1320, 1323 (Fed. Cir. 2000). The disclosure must, nevertheless,
convey with reasonable clarity to ordinarily skilled persons that the inventor
was in possession of the invention at the time of filing. See id.
The Examiner rejected claims 1, 4—8, and 18—22, finding “the
specification does not contain a written description of the claimed invention
. . . [or] reasonably convey to one skilled in the relevant art that the
inventor(s) had possession of the claimed invention at the time the
application was filed.” (Ans. 5.)
2 Mangialaio et al., WO 2006/008183 Al, published Jan. 26, 2006.
3 Rantapaa-Dahlqvist et al., Antibodies Against Cyclic Citrullinated Peptide
and IgA Rheumatoid Factor Predict the Development of Rheumatoid
Arthritis, 48:10 Arthritis & Rheumatism 2741^49 (2003).
4 Nielen et al., Increased Levels of C-Reactive Protein in Serum From Blood
Donors Before the Onset of Rheumatoid Arthritis, 50:8 Arthritis &
rheumatism 2423-27 (2004).
5 Hitchon et al., A Distinct Multicytokine Profile Is Associated with Anti-
Cyclical Citrullinated Peptide Antibodies in Patients with early Untreated
Inflammatory Arthritis, 31:12 The Journal of Rheumatology 2336-46
(2004).
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The Examiner’s position is, in effect, that the Specification and claims
as originally filed fail to support determining the levels of the various
combinations of cytokines and autoantibodies that are presently recited in
the claims. For instance, with respect to claim 4, the Examiner finds “the
specification does not provide support for a method of determining medial
levels of IL-6, at least three (Previously two) additional cytokines, and at
least three autoantibodies.” (Id.)
We are unpersuaded. As Appellants point out, support for the claims
is found throughout the Specification and the original claims. For example,
Appellants identify paragraph 131, which describes arrays with “reagents for
quantification of at least two, at least three, at least four, at least five or more
markers are selected from IP-10 (CXCL-10), MCP-1, CRP, eotaxin, GM-
CSF . . . IL-ip, IL-6, and TNF-a,” thus disclosing numerous combinations
of cytokines. (Br. 6 (citing Spec. 1131).) Appellants identify original
claims 1,2, and 9 as providing support for determining the levels of cytokine
(like IL-6) and at least three autoantibodies. (Id. at 4 (citing original-
dependent claim 9 (“said signature pattern comprises quantitative data for at
least 3 autoantibodies.”).) Appellants further identify Table 11 and Table 12
of the Specification, which describe various combinations of cytokines and
autoantibodies used to test samples. (Br. 7.) This includes, for example,
“Anti-CCP and/or any 2 RFs [thus at least 3 autoantibodies] and >5
cytokines/chemokines positive.” (Spec. 51, Table 11; see also id. at Table
10 (identifying IL-6 among various other cytokines).)
The Examiner provides additional grounds for rejecting the claims
under § 112, first paragraph. (Ans. 6—7.) More specifically, the Examiner
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finds the Specification and original claims fail to provide support for the
comparing step “to generate a determination of prognosis for said
individual” and the step of “providing said individual with said
determination” as recited in claims 1,18, and 19. (Id.) The Examiner
further finds the step of “providing a specific therapeutic agent to treat said
individual” as recited in claim 7 lacks written description support. (Id.)
These additional grounds are also unpersuasive. As Appellants note,
the comparing step to generate a determination of prognosis is supported by
at least paragraphs 98 and 100 of the Specification. (Br. 8; Spec. 98,
100.)6 The Specification expressly discloses that “[t]he resulting
information [i.e., a prognosis] may be transmitted to a patient or health
professional.” (Spec. 1120.) And, after describing numerous therapeutic
agents (see id. at || 73—96), the Specification discloses “biomarkers may
identify patients likely to respond to specific therapeutic agents, and could
thereby be used to guide selection of the most appropriate agent(s) to treat
individual patients” (id. at 197).
In short, Appellants’ disclosure, while broad in many respects, is not
lacking adequate written description as asserted by the Examiner. Based on
the preponderance of the evidence, we are unpersuaded the skilled person
would not recognize possession of (i) the various combinations of cytokines
and autoantibodies for use in Appellants’ claimed method of prognosis, or
6 Certain cites in Appellants’ Brief to paragraphs of the Specification appear
to be one number off. For example, Appellants’ Brief cites to paragraphs 97
and 99 (Br. 8), but the applicable paragraphs appear to be paragraphs 98 and
100. Reference to the Specification in this Decision refers to the version
filed on June 6, 2008.
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(ii) the steps of comparing to generate a prognosis, providing an individual
with the prognosis, or providing a therapeutic agent to treat the individual.
We, thus, reverse the rejections under § 112, first paragraph.
II-INDEFINITENESS
The Examiner finds the term “classification” in claim 19 is vague,
undefined in the Specification, and thus indefinite. (Ans. 4, 11.)
Appellants disagree, citing paragraphs 9 and 11 in the Summary of the
Invention portion of the Specification. Paragraph 9 discloses, in relevant
part, that “methods are provided for prognostic classification of individuals
into subtypes with respect to development of autoimmune disease, which
subtypes are informative of the patient’s probability of developing overt
autoimmune disease.” (Spec. 19 (emphasis added).) Paragraph 11 provides
numerous examples of potential classifications: “with regard to pre-disease
states, one can classify individuals as: normal (N); RF+ anti-CCP- and pre­
disease (RFPD); RF+ anti-CCP- not pre-disease (RFNPD); anti-CCP+ RF-
pre-disease (CCPRFNPD). . . and overt RA (RA).” (Spec. 111.) The
Specification provides further examples of sub-classifications of overt RA
(e.g., “very early disease (< 6 months of symptoms)”). (Id.; see also id. at
1116 (“Classification of interest include, without limitation, the assignment
of a sample to one or more of the autoimmune disease states: i) autoimmune
state vs. non-autoimmune state, (ii) pre-disease vs. normal, (iii) progression
to severe vs. mild disease . . . .”).)
Appellants have the better position. The term “classification” may be
broad, but we are unpersuaded it would not be reasonably understood by
skilled persons when read in light of the Specification. In re Miller, 441
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F.2d 689, 693 (CCPA 1971) (“[BJreadth is not to be equated with
indefiniteness.”) The Examiner has not met the burden to establish that
claim 19 is indefinite. In re Packard, 751 F.3d 1307, 1311 (Fed. Cir. 2014).
Ill - SUBJECT MATTER ELIGIBILITY
Claim 1
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. CLS Bank Inti, 134 S.Ct. 2347, 2355 (2014). According
to that framework, first “we determine whether the claims at issue are
directed to one of those patent-ineligible concepts.” Id. “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,
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).
With the exception of claim 7, addressed separately below, Appellants
argue the patentability of the claims rejected under § 101 as a group. We
select claim 1 as representative. 37 C.F.R. § 41.37(c)(l)(iv).
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The Examiner finds that the invention of claim 1 is drawn to patent-
ineligible subject matter. (Final Act. 8; Ans. 7, 11—14.) More specifically,
the Examiner finds “the methods of the instant claims, determining increased
cytokine and autoantibody levels as a predictor of RA, recite a judicial
exception.” (Final Act. 8.) According to the Examiner, “[t]he steps simply
describe the judicial exception, i.e., the natural relationship between certain
biological markers and the possible development of rheumatoid arthritis.”
(Id.) And, with respect to the claimed steps individually and in combination,
the Examiner finds they “are no more than nominally or insignificantly
related to the judicial exception” and “are conventional and routine within
the art.” (Id.) For example, the Examiner finds that “determining of
cytokine or autoantibody levels, are routinely used by others.” (Id.)
We agree with and adopt the Examiner’s findings of fact, reasoning,
and conclusion that claim 1 is ineligible for patenting under 35 U.S.C. § 101.
(Final Act. 8; Ans. 7, 11—14.) Claim 1 is directed to a law of nature or
natural principle — the correlation between levels of cytokines and
autoantibodies in an individual’s blood sample and the likelihood of that
individual developing rheumatoid arthritis. As Appellants’ Specification
confirms, the invention is, in effect, simply making a prognosis of
rheumatoid arthritis based on this natural correlation. (Spec. Tflf 9—14.)
Turning to step 2 of the Alice/Mayo framework, the claim as a whole,
considering the elements individually and as an ordered combination do not
impart a sufficient inventive concept. As noted by the Examiner, “the
natural correlation of elevated protein marker and autoantibody levels in RA
patients is the only allegedly novel concept set forth in the specification and
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claims.” (Ans. 13.) Indeed, Appellants expressly acknowledge that the
claimed steps relating to determining signature patterns for median levels of
cytokines and autoantibodies involve well-known and conventional assaying
steps known to skilled persons. (See, e.g., Spec. 198 (“A variety of different
assays can be utilized to quantitate the presence of cytokines. Many such
methods are known to one of skill in the art, including ELISA, fluorescence
immunoassays, protein arrays, [etc.]”); see also id. at 1113; Deane Deck 4
(“the rheumatoid factor and anti-CCP2 assays are considered ‘standard’
because they are commercially available”)7.)
The claimed step reciting “comparing said cytokine and autoantibody
signature patterns with a control signature pattern to generate a
determination of prognosis” itself encompasses an abstract mental process.
It is also not materially different than routine steps employed by those
skilled in the art, where cytokine and autoantibody levels in a patient sample
are compared against a healthy control. (See, e.g., Mangialaio 12:13—17
(“increased amounts of the at least two biomarkers and optionally of RF in
the sample from the subject relative to the amounts ... in a control sample
. . . indicates that the subject has or is likely to develop RA”).) 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 a law.”); see also Parker v. Flook, 437 U.S. 584, 590
(1978) (“The notion that post-solution activity, no matter how conventional
7 See the Declaration of co-inventor Kevin Deane, M.D., Ph.D., dated
November 4, 2014 (“Deane Deck”).
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or obvious in itself, can transform an unpatentable principle into a patentable
process exalts form over substance.”)
The step of “providing said individual with said determination of
prognosis” also fails to impart a sufficient inventive concept. This is nothing
more than a generic instruction to apply the natural law — informing the
patient of the prognosis based on the patent-ineligible natural correlation.
Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371, 1377 (Fed. Cir.
2015), cert, denied 136 S.Ct. 2511 (2016) (‘“simply appending conventional
steps, specified at a high level of generality,’ [is] not enough to supply an
inventive concept.”) (quoting Mayo, 132 S.Ct. at 1300); Mayo, 132 S.Ct. at
1294 (“one must do more than simply state the law of nature while adding
the words ‘apply it.’”) (citation omitted).
In short, the claim limitations individually and in combination are
insufficient to transform the patent-ineligible natural law into patent-eligible
subject matter.
We address Appellants’ arguments below:
Appellants contend “others can still apply and use the natural
principle in other methods” for example by “using less than the recited
subset of markers or using alternative markers.” (Br. 12; see also id. at 14
(“others may detect expression of autoantibodies using a method that does
not require a blood sample”.) In other words, Appellants contend that
claim 1 does not preempt all practical applications of the natural principle.
Appellants’ suggestion that complete preemption of all practical
applications of the law of nature is required to sustain a rejection under
§ 101 is unpersuasive. The extent of preemption is a consideration, but the
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absence of complete preemption is not dispositive. On this point, the
Federal Circuit’s analysis in Ariosa is instructive. Ariosa Diagnostics, Inc.
v. Sequenom, Inc., 788 F.3d 1371 (Fed. Cir. 2015), cert, denied 136 S.Ct.
2511 (2016). In Ariosa, the patent owner 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.” (Id. at 1378.) The Federal Circuit rejected that argument
and held that “[wjhile preemption may signal patent ineligible subject
matter, the absence of complete preemption does not demonstrate patent
eligibility.” (Id. at 1379.)8 And, according to the Federal Circuit, “[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.)9
8 See also Ultramercial Inc. v. Hulu LLC, 722 F.3d 1335, 1346 (Fed. Cir.
2013) (“the Supreme Court has stated that, even if a claim does not wholly
pre-empt an abstract idea, it still will not be limited meaningfully if it
contains only insignificant or token pre- or post-solution activity—such as
identifying a relevant audience, a category of use, field of use, or
technological environment.”) (citations omitted), vacated and remanded,
Wildtangent, Inv. v. Ultramercial LLC, 134 S.Ct. 2870 (2014) (remanding
for consideration in light of Alice Corp. Pty. Ltd. v. CLS Banklnt’l, 134
S.Ct. 2347 (2014)).
9 See also Flook, 437 U.S. at 589-90 (rejecting patent applicant’s argument
that “[h]e does not seek to wholly preempt the mathematical formula, since
there are uses of his formula outside the petrochemical and oil-refining
industries that remain in the public domain.”). Updated Patent Office
guidance related to subject-matter eligibility also recognizes that “the courts
do not use preemption as a stand-alone test for eligibility” and instructs that
“while a preemptive claim may be ineligible, the absence of complete
preemption does not guarantee that a claim is eligible.” (See July 2015
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Appellants’ argument fares no better than the similar, but rejected,
argument in Ariosa. Here, as in Ariosa, Appellants’ “attempt to limit the
breadth of the claims by showing alternative uses of [the law of nature]
outside of the scope of the claims does not change the conclusion that the
claims are directed to patent ineligible subject matter.” Ariosa, 788 F.3d at
1379. For claim 1, Appellants determine the levels of IL-6 and at least three
autoantibodies. But we are unpersuaded this makes claim 1 patentable under
Section 101. As discussed above in the Section I, related to the written
description rejection, the Specification discloses numerous potential
combinations of cytokines and autoantibodies that are assayed through
routine techniques. Given this broad disclosure, even if claim 1 did not
foreclose certain combinations of cytokines and autoantibodies at present,
the draftsperson may pursue these combinations through future claims, thus
expanding the preemptive reach of Appellants’ invention drawn to the
natural law.10 Cf. In re BRCA1- and BRCA2-Based Hereditary Cancer Test
PatentLitig., 774 F.3d 755, 764 n. 4 (Fed. Cir. 2014) (“The preemptive
nature of the claims is not ameliorated even if we accept Myriad’s argument
that other methods of comparison exist. If the combination of certain routine
steps were patent eligible, so too would different combinations of other
routine steps.”)
Update on Subject Matter Eligibility, 80 Fed. Reg. 45429 at 8 (July 30,
2015) (footnotes and citations omitted).)
10 Although claim 1 recites “a blood sample,” the Specification discloses that
tissue samples can derive from numerous sources such as synovial fluid,
saliva, milk, urine, and several others. (Spec. 1102.)
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Appellants argue “the elements [of claim 1 ] relate to the natural
principle in a significant way” and it “is clearly an important and practical
application of the alleged natural correlation.” (Br. 12—13.) But even
important and useful discoveries may fail to satisfy § 101. See, e.g.,
Association for Molecular Pathology v. Myriad Genetics, Inc., 133 S.Ct.
2107, 2117 (2013) (“[Myriad] found an important and useful gene . . . [but]
[groundbreaking, innovative, or even brilliant discovery does not by itself
satisfy the § 101 inquiry.”) The method claimed in Mayo, for example, was
useful for determining the efficacy or toxicity of certain drug dosages, yet
the Court held the method was unpatentable because it merely informed the
relevant audience about certain laws of nature with additional steps that
consisted of conventional activity. Mayo, 132 S.Ct. at 1295, 1298.11 The
same is true here. As described above, claim 1 merely appends generic,
routine, and conventional steps that are little more than an instruction to
apply a natural correlation and make a prognosis about rheumatoid arthritis.
Appellants argue “a step of assaying expression levels requires a
transformation of a biological molecule . . . into a detectable signal (e.g., a
fluorescent signal[,] which is detectable by a man-made instrument, e.g., a
PCR machine[)].” (Br. 13.) As an initial matter, claim 1 does not recite any
particular assay or machine required in the process. To the contrary, it
merely recites “determining a cytokine signature pattern for median levels”
of 1L-6 and autoantibodies. The Court in Mayo also rejected a position
11 Cf. Mayo, 132 S.Ct. at 1305 (“We need not determine here whether, from
a policy perspective, increased protection for discoveries of diagnostic laws
of nature is desirable.”)
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similar to the one advanced by Appellants. That is, the Court rejected the
reasoning that the processes were patent eligible because they involve
“transforming the blood by analyzing it to determine metabolite levels.”
Mayo, 132 S.Ct. at 1302-03. In so doing, the Court held that, while the
“machine or transformation” test provides a clue to patentability, it does not
trump the law-of-nature exclusion. Id. at 1303. Here, to the extent there is
any alleged transformation of a biological molecule (e.g., a biomarker in a
blood sample), it involves only an obvious and routine step that applies the
natural law. This fails to transform claim 1 into eligible subject matter. Id.
at 1299 (“Post-solution activity that is purely conventional or obvious . . .
cannot transform an unpatentable principle into a patentable process.”)
(internal quotation marks and alterations omitted).
Inasmuch as Appellants 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”) (Br. 10—14), 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.
Claim 7
Claim 7 depends from claim 1 and adds the step of “providing a
specific therapeutic agent to treat said individual if prognosed with an
increased probability of developing rheumatoid arthritis.” (Br. 22.)
Appellants argue claim 7 satisfies § 101 because it includes a
treatment step. In support, Appellants cite Classen Immunotherapies v.
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Biogen IDEC, 659 F.3d 1057 (Fed. Cir. 2011) and a portion of “Examiner
training slides.” (Br. 14.)
Appellants’ argument is unpersuasive. Classen was decided before
Alice and Mayo and, in view of these later and controlling precedents, does
not support the notion that reciting a treatment step in a claim drawn to a
natural law necessarily transforms the claim into patent-eligible subject
matter. We are not persuaded that appending a generic, routine, and obvious
post-solution treatment step — as recited in Appellants’ claim 7 — provides
a sufficient inventive concept to satisfy § 101. See also Mayo, 132 S.Ct. at
1297 (holding the claimed “‘wherein’ clauses simply tell a doctor about the
relevant natural laws, at most adding a suggestion that he should take those
laws into account when treating his patient.”)
As to the “Examiner training slides” cited by Appellants, these slides
are not the law. In addition, in the very same slide cited by Appellants, it
provides an example of a claim that does recite a law of nature: “Identifying
a disease using a naturally occurring relationship between the presence of a
substance in the body and incidence of disease.”12 This resembles
Appellants’ claims, which are drawn to the natural correlation between
cytokine and autoantibody levels in a blood sample, and the incidence or
prognosis of developing rheumatoid arthritis. Appellants have simply added
a generic step of treating the individual with a therapeutic agent. No new or
12 (See Evaluating Subject Matter Eligibility Under 35U.S.C. § 101: March
2014 Update at slide 21 (slides dated March 19, 2014 available at
https ://www.uspto. gov/patents/law/ exam/ myriad-
may o_slides_20140319.pdf) (last visited May 12, 2017).
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unconventional agent or medical procedure is actually recited. Accordingly,
claim 7 fails to recite patent-eligible subject matter under § 101.
For the reasons above, we conclude the Examiner established by a
preponderance of the evidence that claims 1 and 7 are patent ineligible under
35U.S.C. § 101. Claims 4—6, 8, and 18—22 have not been argued separately
and fall with claim 1.
IV & V - OBVIOUSNESS
Claims 1, 4, and 6—8 Over Mangialaio and Rantapaa-Dahlqvist
Appellants argue the patentability of the claims as a group and we
select claim 1 as representative.
The Examiner finds that Mangialaio “teaches a method for the
prognosis of the development of rheumatoid arthritis.” (Ans. 2.) More
specifically, the Examiner finds that Mangialaio teaches “determining if said
[individual] has significantly increased levels of the cytokines TNF-a, MCP-
1, IL-6, and/or IL-ip, in combination with increased levels of RF (an
autoantibody).” (Id. (citing Mangialaio 12).)
The Examiner finds Mangialaio “differs from the claimed method
only in that it does not teach the employing of an autoantibody pattern of at
least three autoantibodies.” (Id. at 2—3.) The Examiner thus turns to
Rantapaa-Dahlqvist and finds it “teach[es] that the autoantibodies anti-CCP,
IgG-RF, IgM-RF, and IgA-RF are all found at significantly elevated levels
in pre-RA patients.” (Id. at 3 (citing Rantapaa-Dahlqvist Table 1).)
The Examiner concludes it would have been obvious “to perform the
prognosis method of [Mangialaio] including a profile of anti-CCP, IgG-RF,
IgM-RF, and IgA-RF autoantibodies in addition to the profile of the
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cytokines . . . taught by the primary reference.” (Id. at 3.) The Examiner
reasons that the skilled person would have predictably modified the prior art
in this way “to perform a more specific and accurate method of prognosing
the development of RA.” (Id.)
We adopt the Examiner’s fact finding, reasoning, and conclusion that
claim 1 would have been obvious over Mangialaio and Rantapaa-Dahlqvist.
(Ans. 2—3, 14—17.) We address Appellants’ arguments below.
Appellants contend Mangialaio “fails to provide a disclosure that
enables prognosis of disease prior to onset of clinical symptoms, and fails to
teach a combination of multiplex cytokine and multiplex autoantibody
specificities for such a purpose.” (Br. 16.)
We are unpersuaded. As the Examiner correctly points out,
Mangialaio teaches “a method for determining whether a subject has or is
likely to develop rheumatoid arthritis.” (Mangialaio 12:8—9 (emphasis
added); Ans. 14.) Mangialaio does so by assaying levels of at least two
biomarkers (e.g., various cytokines, including IL-6) and RF (an
autoantibody) in a patient sample and comparing against a control sample
from a healthy individual. (Id. at 12:13—20.)13
Although Mangialaio does not expressly teach determining the
amounts of multiple autoantibodies (apparently preferring IgM-RF (see id. at
15:18—19)), that teaching is supplied by Rantapaa-Dahlqvist. (Rantapaa-
Dahlqvist 2741 (“Anti-CCP antibody and RFs of all isotypes predated the
13 Mangialaio teaches “[miniaturized and multiplexed immunoassays may
also used to screen a biological sample for the presence or absence of
proteins such as antibodies.” (Mangialaio 11:8—9.)
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onset of RA by several years. . . . The specificity for RA can be further
increased by combining the presence of anti-CCP antibody with the presence
of rheumatoid factor.”) Table 1 of Rantapaa-Dahlqvist shows the prevalence
of anti-CCP antibodies and IgG, IgM, and IgA RFs in dozens of RA “pre­
patients” meaning those “whose blood samples were obtained before the
onset of any RA symptoms.” {Id. at Table 1.) Rantapaa-Dahlqvist further
teaches “[combining anti-CCP antibodies with any RF isotype increased the
specificity, reaching 100% in some analyses (Table 2).” {Id. at 2745.)
Absent persuasive argument or evidence to the contrary, it would have
been obvious to combine the teachings of Mangialaio and Rantapaa-
Dahlqvist, both of which relate to biomarkers indicating a likelihood of
developing rheumatoid arthritis. Appellants do not persuasively rebut the
Examiner’s reasoning that assaying for additional biomarkers, known for
their association with RA, would have been obvious and would have been
expected to produce more specific and accurate prognoses. (Ans. 3.)
Appellants, citing declaratory evidence, then argue that using
“multiple autoantibodies as well as cytokines and chemokines can be used to
predict the timing of onset of future RA.” (Br. 17.) For example,
Appellants contend certain combinations “could be used to predict
‘imminent’ RA as defined as onset of RA within 2 years.” {Id. at 18.)
Notably, claim 1 is not so narrow and, instead, recites a more general
prognostic method (e.g., “said individual has an increased probability of
developing overt rheumatoid arthritis.”) See also In re Self, 671 F.2d 1344,
1348 (CCPA 1982) (“[AJppellanf s arguments fail from the outset because
. . . they are not based on limitations appearing in the claims.”). In any
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event, the preponderance of the evidence persuades us that combining
Mangialaio and Rantapaa-Dahlqvist in the manner proposed by the
Examiner would predictably allow for a prognosis of the likelihood of
developing RA. Indeed, that is precisely what the references suggest. (See,
e.g., Mangialaio 12:9-29; Rantapaa-Dahlqvist 2741, 2746 (Table 2).)
Appellants contend “results disclosed in the present application
provide for an unexpected benefit.” (Br. 18; Deane Decl. 3.) As noted by
the Examiner, however, “[i]t is unclear if the Inventor intends to actually
claim unexpected results.” (Ans. 16.) Appellants submitted no Reply Brief
to clarity that, in fact, secondary considerations comprising unexpected
results are being alleged. That being said, with respect to the results
Appellants are identifying (Br. 18—20; Deane Decl. 4—8), Appellants have
not shown that such results are commensurate in scope with claim 1 or
reflect more than a difference in degree that would have been expected
based on the combination of known RA-associated biomarkers. In re
Lindner, 457 F.2d 506, 508 (CCPA 1972) (“It is well established that the
objective evidence of nonobviousness must be commensurate in scope with
the claims.”); In re Skoner, 517 F.2d 947, 950 (CCPA 1975) (“Expected
beneficial results are evidence of obviousness of a claimed invention.”). In
short, assaying for multiple cytokines and RA-related autoantibodies may
“lead[] to improved diagnostic accuracy for established disease” as asserted
by Appellants (Br. 20), but we are unpersuaded that provides sufficient
evidence of nonobviousness that outweighs the evidence of obviousness.
The preponderance of the evidence supports the Examiner’s
conclusion that claim 1 would have been obvious over Mangialaio and
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Rantapaa-Dahlqvist. Claims 4 and 6—8 were not argued separately and fall
with claim 1.
Claims 5,19, and 20 Over Mangialaio, Rantapaa-Dahlqvist, Nielen, and
Hitchon
We adopt the Examiner’s findings of fact, reasoning, and conclusion
of obviousness with respect to claims 5, 19, and 20. (Ans. 2-4; 14—18.)
Appellants provide no separate substantive argument in support of the
patentability of claims 5, 19, or 20. Appellants assert that “a combined
profile is significantly more powerful than the sum of its parts” and “[wjhile
any individual marker may have a small predictive ability, the power to
genuinely make a prognosis requires analysis of a complex pattern.” (Br.
21.) These general assertions fail to show error in the Examiner’s
determination of obviousness for the reasons explained above.
SUMMARY
We reverse the rejection of claims 1, 4—8, and 18—22 under 35 U.S.C.
§112, first paragraph, for failure to satisfy the written description
requirement.
We reverse the rejection of claim 19 under 35 U.S.C. § 112, second
paragraph, for indefmiteness.
We affirm the rejection of claims 1, 4—8, and 18—22 under 35 U.S.C.
§ 101 for claiming patent-ineligible subject matter.
We affirm the rejection of claims 1, 4, and 6—8 under 35 U.S.C.
§ 103(a) over Mangialaio and Rantapaa-Dahlqvist.
We affirm the rejection of claims 5, 19, and 20 under 35 U.S.C.
§ 103(a) over Mangialaio, Rantapaa-Dahlqvist, Nielen, and Hitchon.
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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)(l)(iv).
AFFIRMED
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