Ex Parte ROTH et al

Patent Trials and Appeals Board

Apr 3, 2019

12422632 - (D) (P.T.A.B. Apr. 3, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
12/422,632 04/13/2009
33072 7590 04/05/2019
KAGAN BINDER, PLLC
SUITE 200, MAPLE ISLAND BUILDING
221 MAIN STREET NORTH
STILLWATER, MN 55082
UNITED ST A TES OF AMERICA
FIRST NAMED INVENTOR
JOHANNES ROTH
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O. Box 1450
Alexandria, Virginia 22313-1450
www .uspto.gov
ATTORNEY DOCKET NO. CONFIRMATION NO.
IPM0032/US/2 7057
EXAMINER
FOSTER, CHRISTINE E
ART UNIT PAPER NUMBER
1641
NOTIFICATION DATE DELIVERY MODE
04/05/2019 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):
docketing@kaganbinder.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte JOHANNES ROTH and CLEMENS SORG 1
Appeal2018-004056
Application 12/422,632
Technology Center 1600
Before RYAN H. FLAX, RACHEL H. TOWNSEND, and
CYNTHIA M. HARDMAN, Administrative Patent Judges.
HARDMAN, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims to
methods of monitoring the status of a rheumatoid arthritis ("RA") patient
based on the biomarker calgranulin C ("CAL C"), and adjusting the patient's
treatment. The Examiner rejected the claims as being directed to patent-
ineligible 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 Westfaelische Wilhelms-
Universitaet Muenster. (Br. 3.) Herein we reference the Oct. 18, 2017
Appeal Brief ("Br."); the Specification ("Spec.") attached to the Appeal
Brief; the Nov. 17, 2016 Final Office Action ("Final Act."); and the Dec. 22,
2017 Examiner's Answer ("Ans.").
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Application 12/422,632
STATEMENT OF THE CASE
According to the Specification, "there is a need for a reliable
diagnostic tool especially in the early stages of an acute inflammatory
exacerbation and/or for determining the risk of relapse and/or to discriminate
between diseases with similar symptoms in order to apply an appropriate
medication." (Spec. 8:23-26.) Thus, per the Specification, "[t]he present
invention is directed to a method for diagnosing inflammatory diseases,
particularly for diagnosing specific stages of inflammatory diseases and/or
for determining the risk of relapse and/or for discriminating between
diseases with similar symptoms based on the marker CALGRANULIN C."
(Id. at 1 :3-6.)
Claims 43--47, 56, 59, 62, 77, 80-83, 86, and 87 are on appeal. Claim
43 is illustrative and reads as follows:
43. A method for monitoring the status of a patient
suffering from an inflammatory disease, the inflammatory
disease being rheumatoid arthritis, and treating said patient,
comprising steps of:
a) obtaining a serum sample from a rheumatoid arthritis
patient;
b) determining the amount and/or concentration of
CALGRANULIN C polypeptide present in said serum sample;
c) comparing the amount and/ or concentration of
CALGRANULIN C polypeptide determined in said serum
sample with the amount and/or concentration of
CALGRANULIN C polypeptide as determined in a serum
sample obtained at an earlier time from said patient wherein in
said comparison a decrease in the amount and/ or concentration
of CALGRANULIN C polypeptide is representative for an
efficient treatment, and an increase in the amount and/ or
concentration of CALGRANULIN C polypeptide is
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representative for disease exacerbation or of an increased risk
of relapse in said patient; and
d) adjusting treatment of said patient based on said
comparison.
(Br. 28.)
The claims stand rejected as follows:
(a) Claims 43--47, 56, 59, 62, 77, 80-83, 86, and 87 under 35
U.S.C. § 101 as directed to patent-ineligible subject matter. (Final Act. 7.)
(b) Claims 43--47, 56, 59, 62, and 77 under 35 U.S.C. § 103 as
obvious over Trepicchio. 2 (Id. at 13.)
(c) Claims 80-83, 86, and 87 under 35 U.S.C. § 103 as obvious
over Trepicchio and Hellerqvist. 3 (Id. at 23, 25.)
(d) Claims 43--47, 56, 59, 62, and 77 under 35 U.S.C. § 103 as
obvious over Pittman4 and Frosch. 5 (Id. at 19.)
(e) Claims 80-83, 86, and 87 under 35 U.S.C. § 103 as obvious
over Pittman, Frosch, and Hellerqvist. (Id. at 26, 29.)
(f) Claims 43--47, 56, 59, 62, and 77 under 35 U.S.C. § 103 as
obvious over Guild6 and Alters. 7 (Id. at 30.)
2 Trepicchio et al., WO 01/086002 A2, published Nov. 15, 2001.
3 Hellerqvist et al., US 6,028,060, issued Feb. 22, 2000.
4 Pittman et al., US 2003/0154032 Al, published Aug. 14, 2003.
5 Frosch et al., Myeloid-Related Proteins 8 and 14 are Specifically Secreted
During Interaction of Phagocytes and Activated Endothelium and are Useful
Markers for Monitoring Disease Activity in Pauciarticular-Onset Juvenile
Rheumatoid Arthritis, 43(3) ARTHRITIS & RHEUMATISM 628-37 (Mar. 2000).
6 Guild et al., WO 03/060465 A2, published July 24, 2003 (provisional
application filed Dec. 19, 2001).
7 Alters et al., US 2002/0072484 Al, published June 13, 2002.
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(g) Claims 80-83, 86, and 87 under 35 U.S.C. § 103 as obvious
over Guild, Alters, and Hellerqvist. (Id. at 33, 35.)
DISCUSSION
Subject Matter Eligibility
An invention is patent-eligible if it claims a "new and useful process,
machine, manufacture, or composition of matter." 35 U.S.C. § 101.
However, the Supreme Court has long interpreted 35 U.S.C. § 101 to include
implicit exceptions: "[l]aws of nature, natural phenomena, and abstract
ideas" are not patentable. See, e.g., Alice Corp. v. CLS Bankint'l, 573 U.S.
208,216 (2014).
In determining whether a claim falls within an excluded category, we
are guided by the Supreme Court's two-step framework, described in Mayo
and Alice. Id. at 217-18 ( citing Mayo Collaborative Servs. v. Prometheus
Labs., Inc., 566 U.S. 66, 75-77 (2012)). In accordance with that framework,
we first determine what concept the claim is "directed to." See Alice, 573
U.S. at 219 ("On their face, the claims before us are drawn to the concept of
intermediated settlement, i.e., the use of a third party to mitigate settlement
risk.").
If the claim is "directed to" an abstract idea, we tum to the second
step of the Alice and Mayo framework, where "we must examine the
elements of the claim to determine whether it contains an 'inventive
concept' sufficient to 'transform' the claimed abstract idea into a patent-
eligible application." Alice, 573 U.S. at 221 ( quotation marks omitted). A
claim that recites a law of nature must include "additional features that
provide practical assurance that the process is more than a drafting effort
designed to monopolize the law of nature itself." Mayo, 566 U.S. at 77. "A
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patent, for example, [cannot] simply recite a law of nature and then add the
instruction 'apply the law."' Id. at 77-78.
The U.S. Patent and Trademark Office recently published revised
guidance on the application of§ 101. USPTO's 2019 Revised Patent
Subject Matter Eligibility Guidance ("Guidance"). 8 Under that guidance, in
determining what concept the claim is "directed to," we first look to whether
the claim recites:
(1) any judicial exceptions, including certain groupings
of abstract ideas (i.e., mathematical concepts, certain methods
of organizing human activity such as a fundamental economic
practice, or mental processes); and
(2) additional elements that integrate the judicial
exception into a practical application (see MPEP § 2106.05(a}-
(c), (e}-(h)).
Only if a claim (1) recites a judicial exception and (2) does not integrate that
exception into a practical application, do we then look to whether the claim
contains an "'inventive concept' sufficient to 'transform"' the claimed
judicial exception into a patent-eligible application of the judicial exception.
Alice, 573 U.S. at 221 ( quoting Mayo, 566 U.S. at 82). In so doing, we thus
consider whether the claim:
(3) adds a specific limitation beyond the judicial
exception that is not "well-understood, routine, conventional"
in the field (see MPEP § 2106.05(d)); or
8 2019 Revised Patent Subject Matter Eligibility Guidance, 84 Fed. Reg. 50-
57 (January 7, 2019).
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(4) simply appends well-understood, routine,
conventional activities previously known to the industry,
specified at a high level of generality, to the judicial exception.
See Guidance.
We adopt the Examiner's findings and rationale underpinning the
§ 101 rejection (Final Act. 7-12; Ans. 3-8, 31-39), and agree that
Appellants' claimed methods are patent-ineligible.
Step 1, Prong 1
As to the first step of the inquiry under the Guidance, we agree with
the Examiner that the claims recite a judicial exception, namely a law of
nature or natural phenomenon. (Final Act. 7.) As noted above, the claims
recite, "b) determining the amount and/or concentration of CALGRANULIN
C polypeptide present in said serum sample," which is measuring the
amount of CAL C in a sample of serum, and further recite, "c) comparing
the amount and/or concentration of CALGRANULIN C polypeptide
determined in said serum sample with ... a serum sample obtained at an
earlier time from said patient wherein ... a decrease ... is representative for
an efficient treatment, and an increase ... is representative for disease
exacerbation or of an increased risk of relapse in said patient." This claims
the natural relationship between CAL C levels and exacerbation or
progression of RA. This natural relationship to which the claims are
directed is a law of nature. See, e.g., Mayo, 566 U.S. at 1296 (relationships
between concentrations of metabolites in the blood and the likelihood that a
dosage of drug will be ineffective or cause harm was a patent-ineligible law
of nature).
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Appellants argue that the claims are not directed to a natural
phenomenon because "non-natural factors contribute to the etiology of RA
as well as likely variations in certain genetic loci found to be associated with
risk of increased RA." (Br. 14--15.) They cite three references in support of
this argument. (Id. at 14, n.1-3.) We are not persuaded. As an initial
matter, we agree with the Examiner that Appellants have not specifically
pointed out where in the three cited references the relevant teachings are
found. (Ans. 39.) In any event, we adopt the Examiner's statement that
"even if RA might in some cases be triggered by multiple factors some of
which are non-natural, the relation between CAL C and RA/RA status itself
is one that exists in principle apart from any human action." (Id. at 38-39.)
Step 1, Prong 2
Moving to the next inquiry under the Guidance, we find that the
claims do not integrate this law of nature or natural phenomenon into a
practical application. With respect to claims 43 and 80, once the level of
CAL C over time is ascertained, the only practical application of using this
information resides in the claim limitation of "adjusting treatment."
However, like the Examiner, we find that this step
does not clearly call for any specific activity to be performed or
any particular treatment made. Rather, this step when given its
broadest reasonable interpretation merely informs a relevant
audience about the judicial exception, through whatever
process the doctor would wish to use in 'adjusting' treatment;
amounting to general instruction to apply or use the judicial
exception.
(Final Act. 9, emphasis added.) Similarly, we find that the "basing or
altering a treatment scheme" limitation in claim 62 is so general that it
merely amounts to a general instruction to apply or use the judicial
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exception. Such highly generalized treatment limitations-which do not
require any specific treatment for RA----do not amount to sufficient practical
application to provide patentability. As the Supreme Court stated in Mayo,
"simply appending conventional steps, specified at a high level of generality,
to laws of nature ... cannot make those laws ... patentable." Mayo, 566
U.S. at 82.
The level of generality in Appellants' claims stands in contrast to the
treatment claims found patent-eligible in Vanda Pharm. Inc. v. West-Ward
Pharm. Int'! Ltd., 887 F.3d 1117 (Fed. Cir. 2018) and Natural Alternatives
Int'! v. Creative Compounds LLC, 2017 WL 1216226 (Fed. Cir. Mar. 15,
2019). The claims at issue in Vanda recited administering a specific drug
(iloperidone) at specific dosage ranges based on a patient's genotype.
Vanda, 887 F.3d at 1135. Accordingly, the court found that although the
inventors recognized the relationships between iloperidone, a patient's
genotype, and QTc prolongation, what they claimed is "an application of
that relationship," i.e., "'a new way of using an existing drug' that is safer
for patients because it reduces the risk of QTc prolongation." Id. (quoting
Mayo, 566 U.S. at 87). The Federal Circuit characterized the Vanda claims
as being directed to "a specific method of treatment for specific patients
using a specific compound at specific doses to achieve a specific outcome."
Id. at 1136. Similarly, the Federal Circuit found that the claims in Natural
Alternatives "contain specific elements that clearly establish they are doing
more than simply reciting a natural law," such as specifying a patient
population, particular results to be obtained, specific compounds to be
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administered to achieve the claimed results, and dosages via an "effective"
limitation. Natural Alternatives, 2017 WL 1216226, *4--5.
In contrast to the claims at issue in Vanda and Natural Alternatives,
we find that Appellants' claims do not specify a particular result to be
obtained, a compound to be administered to achieve a claimed result, or any
specific dosage of a specific compound. Cf Natural Alternatives, 2017 WL
1216226, at * 5. Instead, we find that the instructions to "adjust treatment"
or "bas[ e] or alter[] a treatment scheme depending on progression of
rheumatoid arthritis" are directed to any and all treatments, including no
treatment at all (discontinuing treatment), based on CAL C levels. In short,
the process does not limit the claim to a particular application; instead the
effect of the treatment limitation of the claims "is simply to tell doctors to
apply the law somehow when treating their patients." Mayo, 566 U.S. at 81-
82.
Step 2
Because the claims (1) recite a judicial exception and (2) do not
integrate that exception into a practical application, we next determine
whether the claims add specific limitation(s) beyond the judicial exception
that are not "well-understood, routine and conventional in the field" (see
MPEP § 2106.05(d)), or whether they simply append well-understood,
routine, conventional activities previously known to the industry, specified
at a high level of generality, to the judicial exception. See Guidance.
In addition to reciting the relationship between CAL C and RA and
the "treatment" limitations discussed above, claims 43 and 80 recite steps of
obtaining a serum sample, determining an amount or concentration of CAL
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C polypeptide in the serum sample, and comparing the amount or
concentration of CAL C to an amount determined in an earlier sample. (Br.
28-30.) Claim 62 similarly recites a "comparing" step. (Id. at 29.) The
Examiner found that measurement of CAL C in blood samples from RA
patients was known, as was a comparison of marker levels relative to
controls, e.g., as disclosed in Pittman and Guild. (Final Act. 9; Ans. 32.)
We adopt these findings and agree with the Examiner that
[t]here is no meaningful limitation, such as a particular or
unconventional machine or a transformation of a particular
article, in the step that distinguishes it from well-understood,
routine, and conventional data gathering activity engaged in by
scientists prior to applicant's invention, and at the time the
application was filed, e.g., the routine and conventional
techniques of detecting a protein by well-known immunoassay
methods.
(Final Act. 10-11.) As stated in Mayo, "[p]urely 'conventional or obvious'
'[pre ]-solution activity' is normally not sufficient to transform an
unpatentable law of nature into a patent-eligible application of such a law."
Mayo, 566 U.S. at 79 (second brackets in original) (citing Parker v. Flook,
437 U.S. 584, 590 (1978)); see also Athena Diagnostics v. Mayo
Collaborative Servs., 915 F.3d 743, 752 (Fed. Cir. 2019) ("Because the
specification defines the individual immunoprecipitation and iodination
steps and the overall radioimmunoassay as conventional techniques, the
claims fail to provide an inventive concept.").
Appellants do not dispute that the individual claimed steps represent
well-understood, conventional, and routine activities, but rather focus on the
"sequence of the diagnosing step followed by the adjusting treatment step,"
arguing that "[a]s an ordered combination the additional element transforms
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the nature of the claim into something significantly more and a patent
eligible application." (Br. 13, emphasis in original.) We are not persuaded
by this argument. Rather, we agree with the Examiner that the evidence of
record indicates that it was well-understood, routine, and conventional to
both measure CAL C and to administer treatments for RA, and in particular
to do both of these steps in combination for the same patient. (Ans. 32.)
Appellants also argue that the claims require a machine or
transformation, e.g., "non-natural mixtures of serum and detection agent,
and the use of machinery to detect and quantify the concentration of CAL C
in the sample." (Br. 14.) Appellants also assert that the step of adjusting
treatment is also "transformative as it alters the subject that has been
diagnosed." (Id.) We are not persuaded by these arguments. First, we find
that the claims do not recite use of any "non-natural compositions of
matter," any particular machinery, or require any alteration to the subject. 9
Limitations not recited in the claims cannot be properly read into the claims.
Second, even if these factors were relevant, "the use of a man-made
molecule is not decisive if it amounts to only a routine step in a conventional
method for observing a natural law." Athena Diagnostics, 915 F.3d at 752.
As described above, the steps of obtaining a serum sample and determining
the amount of CAL C therein were routine steps taught in the art. (See, e.g.,
Spec. 9:22-12: 18, which describes various techniques known in the art that
can be used for determining the amount and/or concentration of CAL C.)
9 We also find that claim 62 does not require that CAL C be measured as
part of the claimed method. Rather, the measurement is indicated to have
been performed previously.
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Appellants next argue that "the claims, taken as a whole, do not
preempt correlating RA with Cal C levels," because they "require diagnostic
information from multiple steps of measurement which accordingly provides
an understanding of the relationship between CAL C concentrations at an
earlier and at a later time point," and because they recite a step of "adjusting
treatment." (Br. 13, emphasis in original.) We are not persuaded by this
argument. We find that the claims do not actually require performing
multiple measurements ( as opposed to comparing multiple measurements),
and moreover, "the naturally occurring correlation is still substantially and
effectively preempted given that for a chronic, ongoing and progressive
disease like RA, it would be the norm to assay a marker at multiple points in
time." (Ans. 34.) Further, we agree that because "the highly general steps
'adjusting treatment' or 'basing or altering a treatment scheme' would
encompass any and all treatments[,] this does not meaningfully address the
issue of preemption as this would effectively preempt all treatments." (Id. at
35.) Finally, "while preemption may signal patent ineligible subject matter,
the absence of complete preemption does not demonstrate patent eligibility."
Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371, 1379 (Fed. Cir.
2015).
For the reasons set forth above, we affirm the rejection of claims 43-
47, 56, 59, 62, 77, 80-83, 86, and 87 under 35 U.S.C. § 101.
Obviousness Rejections Involving Trepicchio and Hellerqvist
The Examiner rejected claims 43--47, 56, 59, 62, and 77 as obvious
over Trepicchio, and claims 80-83, 86, and 87 as obvious over Trepicchio
and Hellerqvist. (Final Act. 13, 23, 25.) We find no error in the Examiner's
determinations on obviousness. We adopt the Examiner's findings of fact
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and rationale regarding the obviousness of the claims over the cited art. (See
id. at 13-16, 17-19, 23-26; Ans. 8-13, 17-20, 39-43, 46-48.) We address
Appellants' arguments below.
With respect to the rejection of claims 43--47, 56, 59, 62, and 77 based
on Trepicchio alone, Appellants assert that Trepicchio is not enabled and/or
is inoperable, particularly in view of the state of the art, which Appellants
assert was highly unpredictable. (Br. 16-18.) Appellants argue that "many
patients with psoriasis develop no arthritis, which argues that there must be
very different biomarkers for psoriatic skin inflammation and arthritis." (Id.
at 17.) Appellants assert that "[ c ]urrent scientific findings reveal RA and
psoriasis have different pathomechanisms and are not THI cell-associated
diseases," which they argue "removes Trepicchio's basis for arguing genetic
markers indicative for psoriasis can also be useful as genetic markers for
RA." (Id. at 16, 17.) Appellants cite articles published in 2016 and 2017,
which they assert show that THI 7 cells, not THI cells, "have been lately
reported as being associated with psoriasis, but not with RA." (Id. at 1 7,
n.4--5.)
Appellants' argument is not persuasive. Even if "recent scientific
information" casts doubt on the accuracy of Trepicchio' s assertion that both
psoriasis and RA are THI-associated diseases, "obviousness is evaluated at
the time of invention, and so it is not clear how such recent information
would address the issue of whether one skilled in the art at the time of the
invention would have viewed the teachings of Trepicchio as unreliable or
unpredictable." (Ans. 42; see also Velander v. Garner, 348 F.3d 1359, 1379
(Fed. Cir. 2003) (noting that obviousness and reasonable expectation of
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success are "measured from the perspective of a person of ordinary skill in
the art at the time the invention was made").) Appellants' arguments and
evidence do not persuade us that, at the time of the invention, persons of
ordinary skill in the art would have had reason to doubt Trepicchio' s
teaching that biomarkers relevant to psoriasis would also be relevant to RA.
Appellants further argue that "[ t ]he identification of a serum protein
biomarker is extremely challenging and associated with a very high level of
unpredictability because there is no certainty that gene upregulation results
in increased presence of the corresponding protein in the serum," and, thus,
"one of skill could not have made any reasonable predictions about serum
proteins as biomarkers based on Trepicchio." (Br. 17 .) They also argue that
"[ m Jost of the upregulated genes of Trepicchio 's gene expression studies,
including two other members of the S 100 family, S 1 OOA2 and S 1 OOA 7 ( see
Tables 6 and 8), have not been found to be useful as serum protein
biomarkers for either psoriasis or RA." (Id. at 18.) We are not persuaded by
these arguments because they are not supported by evidence. See Johnston
v. IVAC Corp., 885 F.2d 1574, 1581 (Fed. Cir. 1989) (noting that attorney
argument is "no substitute for evidence"). Further, Appellants have not
demonstrated that this information would have been known to persons of
ordinary skill in the art at the relevant timeframe, i.e., the time of the
invention.
Finally, Appellants argue that "[ a ]nalysis of Trepicchio' s data
underscores the underlying unpredictability in this technical area." (Br. 18.)
Specifically, they argue that "while skin samples taken from psoriasis
patients show an increased expression of S100A12 (Table 8), gene
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expression in THI-cells (neonatal blood) appears not to be associated with
increased S100A12 expression (Table 5)." (Id.) Appellants' argument is
unclear because we do not find S100A12 listed in either Table 5 or Table 8
of Trepicchio. (Trepicchio 101 (Table 5), 104 (Table 8).) Further, we find
that Appellants' argument is contrary to Trepicchio 's statement that
S100A12 is found in both skin and blood samples: "While several genes
appear in both the skin and blood results (e.g., S100A12 or SCYA4), the
remainder are unique either to the blood results (Table 10) or to the skin
results (Tables 1 and 2)." (Id. at 79:24--26, emphasis added.)
In contrast to claims 43--47, 56, 59, 62, and 77, which are directed to
patients with RA, Appellants' claims 80-84, 86, and 87 are directed to
patients with systemic onset juvenile rheumatoid arthritis ("SOJRA"). The
Examiner rejected claims 80-84, 86, and 87 based on the combination of
Trepicchio and Hellerqvist. Appellants acknowledge that the Examiner cites
Hellerqvist "for its teaching that RA includes any disease that [] meets the
diagnosing criteria set forth by the American Rheumatism Association for
RA, and thus, RA also includes juvenile RA." (Br. 21.) Appellants,
however, argue that "although Hellerqvist discloses that the diagnostic
criteria for RA and juvenile RA may be the same, it does not automatically
mean that monitoring a RA [patient] using a certain serum marker will be
equally suitable for monitoring SOJRA." (Id.) We are not persuaded by this
argument for the reasons given by the Examiner, including because
Appellants do not cite evidence to show that a person of ordinary skill in the
art would have viewed different types of RA as disparate. (Ans. 47--48.)
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With respect to claim 86, Appellants additionally argue that
"Trepicchio is silent with regards to discriminating any disease condition
(including psoriasis or RA) over a bacterial infection." (Br. 21.) This
argument also does not persuade us of error, because as the Examiner
pointed out (and Appellants did not dispute), claim 86 does not require any
active steps relating to such "discrimination." (Final Act. 25; Ans. 47 .)
Rather, we find that because Trepicchio discloses the active method steps
recited in claim 86, the method of Trepicchio would necessarily permit the
"discrimination" recited in claim 86.
With respect to claim 87, Appellants argue that Trepicchio does not
teach SOJRA. (Br. 25.) However, this is not persuasive of error, because as
the Examiner notes, SOJRA is taught by Hellerqvist. (Ans. 48.) "[O]ne
cannot show non-obviousness by attacking references individually where, as
here, the rejections are based on combinations of references." In re Keller,
642 F.2d 413,426 (CCPA 1981).
Obviousness Rejections Involving Pittman, Frosch, and Hellerqvist
The Examiner rejected claims 43--47, 56, 59, 62, and 77 as obvious
over Pittman and Frosch, and claims 80-83, 86, and 87 as obvious over
Pittman, Frosch, and Hellerqvist. (Final Act. 19, 26, 29.) We again adopt
the Examiner's findings of fact and rationale establishing that the claims
would have been obvious over the cited art. (See id. at 19--23, 26-28, 29;
Ans. 13-17, 20-23, 43--46, 48.) We address Appellants' arguments below.
Appellants acknowledge that Pittman teaches that the S 100A12 gene
is over-expressed in RA, but asserts that "one of skill would not have
extrapolated Pittman's data on expression of a certain gene to increased ( or
decreased) presence of the corresponding protein in serum." (Br. 19.) They
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contend that "one of skill could not have made any reasonable predictions
about serum proteins as biomarkers based on Pittman," because "there is no
current scientific information that establishes [that] any of the other genes
identified in Pittman as being upregulated are useful as serum protein
biomarkers for RA." (Id., emphasis added.) Appellants rely on the
discussion of Sekigawa 10 that appears in the February 21, 2014 Declaration
of Johannes Roth. (Id. at 19--20, citing Roth Declaration (Br. Ex. 2) ,r 18.)
According to Appellants, Sekigawa is a "post-filing document" that
"describes changes in serum protein/peptide profiles of infliximab-treated
RA patients using a proteomic research tool." (Br. 19-20.) According to
Appellants:
Aside from S 1 OOA8/ A9, no proteins corresponding to any of
the nineteen different genes found as overexpressed in the
studies of Pittman were identified in the serum of treated RA
patients in the Sekigawa study. If Pittman's gene expressions
studies were an appropriate predictor of the presence of the
corresponding proteins in serum of treated RA patients, one of
skill would expect most or all of Pittman's proteins to be
represented in Figure 2 of Sekigawa.
(Id. at 20.)
Similar to the discussion above regarding the 2016 and 2017 "recent
scientific information," this argument does not persuade us of error, because
it is not grounded in the appropriate timeframe. Sekigawa is dated many
years after Appellants' priority date. Appellants have not persuaded us that,
at the time of the invention, persons of ordinary skill in the art would have
10 Sekigawa et al., Protein Biomarker Analysis by Mass Spectrometry in
Patients With Rheumatoid Arthritis Receiving Anti-Tumor Necrosis Factor-a
Antibody Therapy, 26 CLIN. EXP. RHEUMATOL. 261---67 (2008).
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had reason to doubt Pittman's teachings that the level of expression of genes
such as S100A12 could be detected by measuring the level of protein
encoded by the gene. (Pittman ,r,r 22, 179.)
With respect to Frosch, Appellants acknowledge that this reference
"describes two other S 100 proteins, A8 and A9 ... which ... are present in
the serum at concentrations useful as markers for monitoring local
inflammation in JRA Uuvenile rheumatoid arthritis]." (Br. 20.) Appellants
argue, however, that "the information that Cal C is a member of S 100
proteins was not sufficient at the time of the invention to predict that it also
would have been useful as a maker [sic] for monitoring local inflammation
in JRA," because there are few "structural or functional commonalities with
members of the S 100 protein family." (Id.)
The Examiner responded that:
This is not found persuasive because the rejection is not
based on Frosch alone, and so the issue at hand is not whether
one would predict from Frosch that CAL C is a marker of JRA.
Rather, Pittman already identifies CAL Casa marker of RA,
and further teaches that it can be measured in blood. There is
nothing that would clearly cast doubt on this teaching, and so it
is maintained that one skilled in the art would have reasonably
expected CAL C to be detectable in blood as taught by Pittman.
It was also well known in the prior art that serum is blood with
the clotting factors removed, and CAL C was known not to be a
clotting factor. Accordingly, one skilled in the art would have
reasonably expected to find CAL C in blood serum; and Frosch
provides additional direction to serum in establishing that other
family members are present in serum in the context of RA.
Appellant does not point to evidence supporting that 39%
identity would have been viewed as corresponding to "little
structural or functional commonalities", but regardless of
sequence homology, it is evident that CAL C was viewed in the
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prior art to have commonalities as it is identified as a
recognized member of this known family of proteins.
(Ans. 46.)
We adopt the Examiner's findings and reasoning, and agree that
because the rejection is not based on Frosch alone, the issue at hand is not
whether one would have predicted from Frosch that CAL C is a marker of
JRA. Pittman already identifies the CAL C gene as a marker of RA (e.g.,
Pittman ,r 22), and further teaches that the level of gene expression can be
measured by measuring protein in blood (e.g., id. at ,r,r 85, 179). Appellants
have not persuaded us that a person of ordinary skill in the art at the time of
the invention would have had reason to doubt these teachings. We agree
with the Examiner's findings that, because serum is blood with the clotting
factors removed, and CAL C was not known to be a clotting factor, one of
ordinary skill in the art would have reasonably expected to find CAL C in
blood serum. (Ans. 46; see also 45.) We also agree with the Examiner's
findings that Frosch provides additional direction to serum in establishing
that other family members are present in serum in the context of RA. (Id. at
46.) Accordingly, for this reason and the other reasons provided by the
Examiner, Appellants' arguments regarding Frosch do not persuade us of
any Examiner error.
With respect to the addition of Hellerqvist for claims 80-84, 86, and
87, Appellants make arguments similar to those made with respect to the
Trepicchio-based rejections. (See Br. 22-23.) We do not find these
arguments persuasive, for the same reasons discussed above.
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Obviousness Rejections Involving Guild and Alters
The Examiner rejected claims 43--47, 56, 59, 62, and 77 as obvious
over Guild and Alters, and claims 80-83, 86, and 87 as obvious over Guild,
Alters, and Hellerqvist. (Final Act. 30, 33, 35.)
Appellants first argue that the Examiner relies on disclosure in Guild
WO 03/060465 ("Guild '465") that is not present in Guild's provisional
application (US 60/341,942, "Guild Provisional '942"). (Br. 24.)
Appellants argue that this is improper because Guild '465 has an
international filing date (17 December 2002) and publication date (24 July
2003) falling after Appellants' priority date, which the Office acknowledged
to be February 15, 2002 (the filing date ofUS 10/077,600). (Id.)
Appellants, therefore, assert that if the rejections based on Guild are
maintained, they should be based on its disclosure only to the extent it is
supported in Guild Provisional '942. (Id.)
In response, the Examiner noted that Appellants' petition regarding its
priority claim was filed and decided after mailing of the Final Rejection.
(Ans. 48--49.) The Examiner then cited disclosure from Guild Provisional
'942 that was determined to have rendered the claims obvious. (Id. at 23-
30, 48-50.)
We agree that to be used as prior art, disclosure in Guild '465 must
find support in Guild Provisional '942. See MPEP § 2136.03(II) (discussing
critical reference date for international applications that claim priority from
US provisional applications). Here, we find that the Examiner has relied on
disclosure in Guild '465 that is sufficiently supported in Guild Provisional
'942 to support the rejections. As such, we again adopt the Examiner's
findings and rationale establishing that the claims would have been obvious
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over Guild and Alters (claims 43--47, 56, 59, 62, and 77) and Guild, Alters,
and Hellerqvist (claims 80-83, 86, and 87). (Ans. 23-30, 48-50.)
Appellants argue that "Guild [Provisional] '942 only provides
experimental results of a study of a vast number of proteins that are
upregulated in synovial fluid (not human serum)," and that "Guild
[Provisional] '942 only mentions serum generically, but does not even
suggest that S100A12 should be tested according to the methods of the
current disclosure." (Br. 24, emphasis in original.) We are not persuaded.
We agree with the Examiner that Guild teaches that the disclosed methods of
assessing the amount or concentration ofbiomarkers, including proteins, can
be carried out using serum samples. (See Ans. 49, citing Guild Provisional
'942 at, e.g., 17:19-25, 19:18-21; Guild '465 at 16:17-23.) Appellants have
not persuaded us that persons of ordinary skill in the art at the time of the
invention would have had reason to doubt these teachings. See Johnston,
885 F.2d at 1581 (noting that attorney argument is "no substitute for
evidence").
Appellants further argue that Guild Provisional '942 does not suggest
that S 1 OOA12 should be tested according to the disclosed methods,
particularly because it "describes that its Table 4 has markers especially
useful for new detection ('screening') and detection of recurrence of RA, but
S1001A12 is not listed in Table 4." (Br. 24--25, emphasis in original.)
Appellants' argument is not persuasive. As the Examiner found, S 100A12 is
listed in Tables 1 and 2, which identify proteins that are useful as markers of
RA. (See Ans. 49; Guild Provisional '942 at 94: 16-20, Tables 1 and 2;
Guild '465 at 13: 17-21, Tables 1 and 2.) Moreover, contrary to Appellants'
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assertion, Table 4 of Guild Provisional '942 does in fact disclose S100A12.
Table 4 of Guild Provisional '942 is reproduced below:
Tabfo4
Table 4 provides a list of markers obtained using the protocol described in
Guild. Guild Provisional '942 at 94. Row 1 in Table 4 recites "S100A12
protein." See also Guild '465 at Table 4.
Finally, Appellants argue that Guild Provisional '942 does not teach
that "an increase in CAL C is useful for indicating disease exacerbation or
risk of relapse [in] rheumatoid arthritis." (Br. 25.) We are not persuaded by
this argument. Rather, we agree with the Examiner that
while not explicitly taught in these terms, this is believed to be
obvious as Guild teaches that the marker is elevated in the
disease state and that a decrease indicates effective therapy.
Accordingly, while Guild may not explicitly state the converse
situation, it is maintained that in view of these teachings it
would have been obvious to correlate an increase in levels after
treatment as indicating disease exacerbation or risk of relapse.
(Ans. 49.) Moreover, Guild Provisional '942 teaches that the disclosed
markers can be used to monitor the progression of RA in a patient, and that
"[a] significantly higher level of expression of the marker in the sample at
the subsequent time point from that of the sample at the first time point is an
indication that the RA has progressed." (Guild Provisional '942, 5:24---6:2;
see also Guild '465 at 15:18-21.) Accordingly, we find that Guild does
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disclose that an increase in CAL C is useful for indicating disease
progression, i.e., disease exacerbation.
As to Alters, Appellants argue that it does not discuss CAL C. (Br.
25.) This argument is not persuasive because, as the Examiner notes, CAL
C is taught by Guild, which is used in combination with Alters. (Ans. 49.)
Again, Appellants cannot show non-obviousness by attacking references
individually. In re Keller, 642 F .2d at 426.
With respect to the addition of Hellerqvist for claims 80-84, 86, and
87, Appellants make arguments similar to those made with respect to the
Trepicchio-based rejections. (See Br. 26.) We do not find these arguments
persuasive, for the same reasons discussed above.
Aside from claims 86 and 87 (which are addressed above), Appellants
have not separately argued patentability based on the additional limitations
of dependent claims 44--47, 56, 59, 77, and 81-83. Accordingly these
claims fall for the same reasons discussed above. 37 C.F.R.
§ 4I.37(c)(l)(iv).
SUMMARY
We affirm the rejection of claims 43--47, 56, 59, 62, 77, 80-83, 86,
and 87 under 35 U.S.C. § 101 as directed to patent-ineligible subject matter.
We affirm the rejection of claims 43--47, 56, 59, 62, and 77 under
35 U.S.C. § 103 as obvious over Trepicchio.
We affirm the rejection of claims 80-83, 86, and 87 under
35 U.S.C. § 103 as obvious over Trepicchio and Hellerqvist.
We affirm the rejection of claims 43--47, 56, 59, 62, and 77 under
35 U.S.C. § 103 as obvious over Pittman and Frosch.
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We affirm the rejection of claims 80-83, 86, and 87 under
35 U.S.C. § 103 as obvious over Pittman, Frosch, and Hellerqvist.
We affirm the rejection of claims 43--47, 56, 59, 62, and 77 under 35
U.S.C. § 103 as obvious over Guild and Alters.
We affirm the rejection of claims 80-83, 86, and 87 under 35
U.S.C. § 103 as obvious over Guild, Alters, and Hellerqvist.
TIME PERIOD FOR RESPONSE
No time period for taking any subsequent action in connection with
this appeal may be extended under 3 7 C.F .R. § 1.13 6( a )(1 )(iv).
AFFIRMED
24