Ex Parte Raman et al

Patent Trial and Appeal Board

Nov 6, 2018

12811292 (P.T.A.B. Nov. 6, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
12/811,292 07/30/2010 Subha V. Raman
96039 7590 11/08/2018
Meunier Carlin & Curfman LLC
999 Peachtree Street NE
Suite 1300
Atlanta, GA 30309
UNITED ST A TES OF AMERICA
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.
10336-151US 1 4911
EXAMINER
BROWE, DAVID
ART UNIT PAPER NUMBER
1617
NOTIFICATION DATE DELIVERY MODE
11/08/2018 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@mcciplaw.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte SUBHA V. RAMAN, ORLANDO P. SIMONETTI,
and JAY L. ZWEIER 1
Appeal2017-001873
Application 12/811,292
Technology Center 1600
Before MICHAEL J. FITZPATRICK, RICHARD J. SMITH, and
TA WEN CHANG, Administrative Patent Judges.
SMITH, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a method
for in vivo characterization of atherosclerotic plaque. We have jurisdiction
under 35 U.S.C. § 6(b).
We affirm the rejection under Section 103 for obviousness and reverse
the rejection under Section 101 for non-statutory subject matter.
1 According to Appellants, the real party in interest is Ohio State Innovation
Foundation. (Appeal Br. 3.)
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Application 12/811,292
STATEMENT OF THE CASE
Claims on Appeal2
Claims 1, 2, 4, and 19 are on appeal. (Claims Appendix, Br. 10-11.)
Claims 1 is illustrative and reads as follows:
1. A method for in vivo atherosclerotic plaque characterization in
a subject in need thereof, comprising:
identifying an atherosclerotic plaque in a subject;
conducting a magnetic resonance imaging (MRI) of the
atherosclerotic plaque in vivo in the subject using a MRI device;
incorporating a double inversion blood suppression pre-
imaging pulse into T2 * magnetic resonance imaging (MRI)
mapping using the MRI device;
incorporating a chemical shift selective fat suppression
pre-imaging pulse into T2* MRI mapping using the MRI device;
detecting a level of endogenous iron Fe(III) complexes in
the atherosclerotic plaque in the subject by measuring T2*,
wherein no iron-containing contrast agent is used;
characterizing the atherosclerotic plaque for intraplaque
iron content of Fe(III); and
distinguishing symptom-producing atherosclerotic plaque
from non-symptom producing atherosclerotic plaque in the
subject when Fe(III) levels are higher in non-symptom-
producing atherosclerotic plaque than in symptom producing
plaque.
2 The Examiner identifies Appellants' elected subject matter as "directed to a
method for characterizing an atherosclerotic plaque comprising i) detecting
the level of endogenous iron (III) complexes in the atherosclerotic plaque by
T2* magnetic resonance imaging (MRI) with a non-iron contrast agent using
double inversion blood suppression and fat suppression, ii) comparing the
detected value to a reference value, and iii) drawing conclusions about the
vulnerability of the plaque." (Final Office Action mailed Jan. 12, 2015,
("Final Act") 4; see also Response to Restriction Requirement dated July 23,
2012.) We limit discussion and consideration to the elected species. See Ex
parte Ohsaka, 2 USPQ2d 1460, 1461 (BP AI 1987).
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Examiner's Rejections
1. Claims 1, 2, 4, and 19 stand rejected under 35 U.S.C. § 103(a) as
unpatentable over Yuan, 3 Anderson, 4 and Stadler. 5 (Final Act. 4---6.)
2. Claims 1, 2, 4, and 19 stand rejected under 35 U.S.C. § 101 because
the claimed invention is directed to non-statutory subject matter (a natural
principle). (Id. at 2-3.)
DISCUSSION
We adopt the Examiner's findings, analysis, and conclusions
regarding the obviousness rejection, including with regard to the scope and
content of, and motivation to combine, the prior art, as set forth in the Final
Action and Answer. We discern no error in the rejection of the claims as
obvious.
Rejection No. 1
Issue
Whether a preponderance of evidence of record supports the
Examiner's rejection under 35 U.S.C. § 103(a).
Principles of Law
The test for obviousness is "what the combined teachings of the
references would have suggested to those of ordinary skill in the art" and not
3 C. Yuan et al., MRI of Atherosclerosis, J. Magnetic Resonance Imaging
19, 710-19 (2004) ("Yuan").
4 L.J. Anderson et al., Cardiovascular T2-star (T2*) magnetic resonance for
the early diagnosis of myocardial iron overload, European Heart J., The
European Soc'y of Cardiology 22, 2171-79 (2001) ("Anderson").
5 N. Stadler et al., Direct Detection and Quantification of Transition Metal
Ions in Human Atherosclerotic Plaques: Evidence of the Presence of
Elevated Levels of Iron and Copper, Arteriosclerosis, Thrombosis, and
Vascular Biology, J. Am. Heart Ass'n 24, 949-54 (2004) ("Stadler").
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"that the claimed invention must be expressly suggested in any one or all of
the references." In re Keller, 642 F.2d 413,425 (CCPA 1981) (citing cases).
An obviousness analysis "need not seek out precise teachings directed
to the specific subject matter of the challenged claim, for a court can take
account of the inferences and creative steps that a person of ordinary skill in
the art would employ." KSR Int'! Co. v. Teleflex Inc., 550 U.S. 398,418
(2007).
Analysis
Claims 1 and 19 are the only independent claims on appeal and recite
similar limitations. We limit our consideration to claim 1 because the claims
were not argued separately.
Examiner's Position
The Examiner finds that Yuan discloses a method for characterizing
atherosclerotic carotid plaque using MRI techniques, with or without
gadolinium (a non-iron contrast agent), and further using double inversion
blood suppression and fat suppression, to detect plaque constituents and
composition, comparing MRI data to standard references, and identifying
vulnerable plaque. (Final Act. 4.) The Examiner also finds that Anderson
discloses the use of T2*-MRI to detect endogenous tissue iron levels, and
that Stadler discloses the detection of elevated endogenous carotid plaque
iron (III) complexes, that positively correlate with plaque cholesterol levels
and disease progression, and that elevated iron (III) levels may affect plaque
stability and propensity to rupture. (Final Act. 5.)
Based on those findings, the Examiner concludes that the claims
would have been prima facie obvious, and that
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one of ordinary skill in the art would be motivated to
characterize an atherosclerotic carotid plaque by employing
T2*-MRI techniques with or without a gadolinium (i.e. non-
iron) contrast agent using double inversion blood suppression
and fat suppression to detect endogenous iron (III) within the
plaque, and comparing MRI data to standard references, with
the reasonable expectation that the resulting technique will
successfully correlate with disease progression and identify
vulnerable plaque.
(Final Act. 5---6.)
We find that the Examiner has established a prima facie case of
obviousness based on the combined teachings of Yuan, Anderson, and
Stadler. (Id. at 4--6.)
Appellants 'Arguments
Appellants argue that Anderson does not remedy the deficiencies of
Yuan because Anderson only teaches using the T2 *-MRI on heart tissue,
and that there is no teaching or suggestion in Anderson that a non-tissue
material, such as plaque, can be examined in vivo within a tissue such as a
carotid artery. (Br. 7 .) Appellants also argue that there is no correlation
suggested in Anderson "between heart iron levels [in] thalassemia major
patients and the intraplaque Fe(III) levels in atherosclerotic patients" or
between cardiomyopathy and symptom-producing atherosclerosis. (Id.)
We are not persuaded. We note that the rejection is based on the
combined teachings of Yuan, Anderson, and Stadler, and not just on Yuan
and Anderson. See Keller, 642 F.2d at 425. Yuan teaches the use of MRI to
examine plaque in vivo, and Anderson is cited for the use of T2*-MRI to
detect endogenous tissue iron levels. (Final Act. 5; see also Anderson 2171
("We have developed a new magnetic resonance T2-star (T2 *) technique for
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the measurement of tissue iron."). The Examiner also relies on Stadler (not
Anderson) for the correlation of "intraplaque Fe(III) levels in atherosclerotic
patients." (See Br. 7; see also Final Act. 5.)
Although the working example in Anderson may be directed to
myocardial tissue and cardiomyopathy, Anderson may still be cited because
a prior art reference is not limited to its working examples, In re Mills, 470
F.2d 649, 651 (CCPA 1972), and "'[a] reference must be considered not
only for what it expressly teaches, but also for what it fairly suggests"' In re
Baird, 16 F.3d 380, 383 (Fed. Cir. 1994) (quoting In re Burckel, 592 F.2d
1175, 1179 (CCPA 1979)). Here, Anderson fairly suggests the use of T2*-
MRI in the in vivo detection of iron levels in body tissue. (See Ans. 10-11.)
We are also unpersuaded by Appellants' distinction between tissue and
plaque, based at least on Yuan's numerous references to "plaque tissue."6
(See, e.g., Yuan 710-12 and 717.)
Appellants argue that Stadler "only describes the use of electron
paramagnetic resonance (EPR) spectroscopy and inductive coupled plasma
mass spectroscopy (ICPMS) to quantify ex vivo carotid lesions," and that
"[t]hus, there is no teaching or suggestion in Stadler[] for the conducting of
an in vivo MRI on the subject itself," or "that any tissue could be examined
in vivo." (Br. 7-8.) We are not persuaded. The combination of Yuan and
Anderson teaches the use of T2*-MRI for conducting in vivo analysis of
tissue such as plaque.
6 See also definition of plaque: "A thickened area consisting of fibrous
tissue and lipid, often with calcification, in the intima of an atherosclerotic
artery." (emphasis added). Oxford English Dictionary,
http://www.oed.com/view/Entry/145203?redirectedFrom=plaque#eid, last
visited Oct. 30, 2018.
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Appellants also argue that "Stadler[] does not distinguish[] 'symptom-
producing atherosclerotic plaque' as compared to 'non-symptom producing
atherosclerotic plaque.' Nor does Stadler[] teach or suggest that Fe(III) is
lower in symptom-producing atherosclerotic plaque than in non-symptom
producing plaque." (Br. 8.) According to Appellants, Stadler teaches the
"exact opposite" of the correlation recited by Appellants, citing Stadler' s
statement that "[t]he g:::::;4 Fe(III) species was quantified, and although the
levels varied (Figure IB), the mean value for all the plaques examined is
significantly elevated over that detected in health[y] intima samples." (Id.,
quoting Stadler 951 (emphasis added).) Appellants further argue that the
Examiner is applying a Section 101 analysis to the "distinguishing" step
because the correlation between endogenous plaque iron (III) levels and
"symptoms" is a natural phenomenon that is not patentable subject matter.
(Br. 8.) According to Appellants, a Section 101 analysis has no bearing in a
Section 103 analysis of "determining whether a claim defines over the prior
art." (Id.)
We are not persuaded. Stadler is cited for teaching a correlation
between iron (III) levels in plaque and disease progression (Final Act 5), and
Stadler concludes that "[ t ]hese data support the hypothesis that iron
accumulates in human lesions and may contribute to disease progression."
(Stadler Abstract.) Appellants' Specification also states that "the term
'harmful or symptom-producing plaque' can generally include the presence
of plaque that produces one or more atherosclerotic symptoms in a subject"
(Spec. ,r 10), which can reasonably be interpreted to mean plaque that "may
contribute to disease progression" (Stadler Abstract). We are thus not
persuaded by the argument that Stadler does not distinguish "symptom-
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producing atherosclerotic plaque from non-symptom producing
atherosclerotic plaque" as recited in claim 1.
Appellants also argue that Stadler teaches a correlation between
plaque iron levels and disease progression that is opposite to that claimed by
Appellants. (Br. 8.) However, as Appellants point out, Stadler's example is
not in vivo and does not use T2*-MRI. (Id. at 7.) Appellants' Specification
also distinguishes inductively coupled plasma mass spectroscopy and
electron paramagnetic resonance ( that Appellants argue is used by Stadler)
from T2*-MRI. (Spec. ,r,r 7-8.) Stadler's and Appellants' respective
correlations are thus not directly comparable, but a direct comparison is not
required for obviousness. (See also Spec. ,r 6 ("[S]tudies relating to iron and
atherosclerosis have provided conflicting results.").) Moreover, Stadler's
conclusion regarding "the hypothesis that iron accumulates in" plaques and
that iron accumulation "may contribute to disease progression" ( emphasis
added) is a suggestion to correlate iron levels to distinguish symptom
producing plaque versus non-symptom producing plaque (as taught by
Stadler and relied on by the Examiner), but is not a definitive statement of
what that correlation may be. Stadler is thus an appropriate reference to
combine with Yuan and Stadler to render claim 1 prima facie obvious.
Appellants' blanket contention that a Section 101 analysis has no
bearing in a Section 103 analysis is incorrect. See Praxair Distribution, Inc.
v. Malllinckrodt Hosp. Prods. IP Ltd., 890 F.3d 1024, 1032-34 (Fed. Cir.
2018) ( citing cases). Although Praxair addressed printed matter limitations
in the context of an obviousness analysis, it also applied the same analysis to
mentally-processed information. Id. at 1033-34. Here, the step of
distinguishing plaque based on Fe(III) levels is taught by the prior art
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(Stadler). The correlation of iron levels in symptom-producing plaque as
compared to non-symptom producing plaque is a natural phenomenon, and
is not accorded any patentable weight, at least because that natural
phenomenon is analyzed using "information [(i.e., the correlation)] together
with a purely mental step [(i.e., comparing Fe(III) levels)]." See Praxair,
890 F.3d at 1033-34. Moreover, "[s]cientific confirmation of what was
already believed to be true may be a valuable contribution, but it does not
give rise to a patentable invention." PharmaStem Therapeutics, Inc. v.
ViaCell, Inc., 491 F.3d 1342, 1347, 1363---64 (Fed. Cir. 2007) (reversing
nonobviousness of claims that were based on the discovery that human
umbilical cord blood could be used as a source of transplantable
hematopoietic stem cells); see Spec. ,r,r 4--7.
We are also unpersuaded by Appellants' "impermissible hindsight"
argument. (Br. 6, 8.) It is well-established that any judgment on
obviousness is in a sense necessarily a reconstruction based upon hindsight
reasoning, "but so long as it takes into account only knowledge which was
within the level of ordinary skill at the time the claimed invention was made
and does not include knowledge gleaned only from applicant's disclosure,
such a reconstruction is proper." In re McLaughlin, 443 F.2d 1392, 1395
( CCP A 1971 ). Appellants adduce no evidence that the Examiner's findings
were beyond the level of ordinary skill in the art at the time of invention, nor
do they point to any of the Examiner's findings that could have been taken
only from Appellants' Specification.
Accordingly, for the reasons of record and as set forth above, we
affirm the rejection of claim 1 for obviousness. Claims 2, 4, and 19 were not
argued separately and fall with claim 1.
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Rejection No. 2
Issue
Whether a preponderance of evidence of record supports the
Examiner's rejection under 35 U.S.C. § 101.
Analysis
The Examiner's statement of rejection reads as follows:
The above identified claims are in fact directed to a natural
principle since they are based merely on detecting the level of
endogenous iron (III) complexes in plaque using an established,
conventional technique (i.e. MRI imaging), comparing the
detected value to a reference value, and drawing conclusions.
The claimed subject matter thus amounts to diagnosing or
"characterizing" a condition based on a naturally occurring
relationship or correlation between the presence or level of an
endogenous substance when a condition/disease is present, and
do not include additional elements or steps that amount to
significantly more than the natural principle itself. Applicant is
detecting the endogenous iron (III) by a generic "T2*-MRI
imaging" method, which method is well known in the art for
detecting tissue iron levels. Thus, the manner in which the
endogenous iron (III) is being detected is commonplace, and
comparing numbers and drawing conclusions are nothing more
than abstract mental processes (i.e. "thinking").
(Final Act. 2-3.)
Appellants refer to the 2014 Interim Guidance on Patent Subject
Matter Eligibility7 to argue that "applying Step 2B, the Appellant[s] note[]
that the claims recite 'significantly more' [than] the judicial exception when
the claims are analyzed as a whole." (Br. 5---6.) Appellants proceed to
identify the steps that follow the step of identifying an atherosclerotic plaque
7 https://www.federalregister.gov/documents/2014/12/16/2014-29414/2014-
interim-guidance-on-patent-subject-matter-eligibility.
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in a subject, and conclude that the Examiner erred in concluding that the
claims "fail to meet at least Step 2B of the Alice/Mayo two-part test." (Br.
6.) The Examiner responds to Appellants' contention by stating that the
claimed steps were "well known" based on the respective references of
Yuan, Anderson, and Stadler. (Ans. 7-8.)
"[T]he examiner bears the initial burden, on review of the prior art or
on any other ground, of presenting aprimafacie case ofunpatentability." In
re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992). We find in this case that
the Examiner has failed to meet that burden.
Since the docketing of this appeal in December 2016, the Federal
Circuit issued its decision in Berkheimer v. HP Inc., 881 F.3d 1360 (Fed.
Cir. 2018), after which the US PTO published an examination procedure
entitled "Changes in Examination Procedure Pertaining to Subject Matter
Eligibility, Recent Subject Matter Eligibility Decision (Berkheimer v. HP,
Inc.)" (hereinafter "PTO Memorandum"). 8 The PTO Memorandum clarifies
that a conclusion that an element ( or combination of elements) represents
well-understood, routine, conventional activity must be based on a factual
determination as set forth in Section III of the PTO Memorandum. Section
III.A.3. is pertinent here, and reads as follows ( emphases and formatting
added):
3. A citation to a publication that demonstrates the well-
understood, routine, conventional nature of the additional
element(s). An appropriate publication could include a book,
manual, review article, or other source that describes the state
of the art and discusses what is well-known and in common use
in the relevant industry. It does not include all items that might
8 https://www.uspto.gov/sites/default/files/documents/memo-berkheimer-
20180419.PDF.
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otherwise qualify as a "printed publication" as used in 35
U.S.C. § 102.[]
Whether something is disclosed in a document that is
considered a "printed publication" under 35 U.S.C. § 102 is a
distinct inquiry from whether something is well-known, routine,
conventional activity. A document may be a printed
publication but still fail to establish that something it describes
is well-understood, routine, conventional activity. See Exergen
Corp., 2018 WL 1193529, at *4 (the single copy of a thesis
written in German and located in a German university library
considered to be a "printed publication" in Hall "would not
suffice to establish that something is 'well-understood, routine,
and conventional activity previously engaged in by scientists
who work in the field'").
The nature of the publication and the description of the
additional elements in the publication would need to
demonstrate that the additional elements are widely prevalent
or in common use in the relevant field, comparable to the types
of activity or elements that are so well-known that they do not
need to be described in detail in a patent application to satisfy
35 U.S.C. § 112(a). For example, while U.S. patents and
published applications are publications, merely finding the
additional element in a single patent or published application
would not be sufficient to demonstrate that the additional
element is well-understood, routine, conventional, unless the
patent or published application demonstrates that the
additional element are widely prevalent or in common use in
the relevant field.
(PTO Memorandum III.A.3 (internal citations omitted).)
On the record before us, we have the Examiner's conclusory
statement of rejection that the claims "do not include additional elements or
steps that amount to significantly more than the natural principle itself,"
based on the unsupported statement that the '"T2 *-MRI imaging' method
... is well known in the art for detecting tissue iron levels." (Final Act. 3.)
The Examiner elaborates on that finding in the Answer by citing to
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Anderson as support for the statement that "[ e ]mploying T2 * MRI to detect
iron (III) levels in the body is well known." (Ans. 8.)
Simply stated, we cannot reconcile the requirements of the PTO
Memorandum with the unsupported statement in the Final Action regarding
T2*-MRI imaging, and the insufficient statement regarding T2*-MRI
imaging in the Answer. Rather than describing that T2*-MRI imaging is
well known and in common use in the relevant industry, Anderson states that
"[ w ]e have developed a new magnetic resonance T2-star (T2 *) technique for
the measurement of tissue iron." (Anderson 2171 (emphasis added).)
Although that teaching may be used in an obviousness analysis, we do not
find on this record that it satisfies the required showing that the use of T2 *-
MRI imaging for detecting tissue iron levels was "widely prevalent or in
common use in the relevant field" at the time of the invention. 9 (PTO
Memorandum III.A.3.)
We find that the Examiner has failed to establish a prima facie case of
non-statutory subject matter. Accordingly, we reverse the rejection of
claims 1, 2, 4, and 19 under 35 U.S.C. § 101.
Conclusions of Law
A preponderance of evidence of record supports the Examiner's
rejection of claims 1, 2, 4, and 19 under 35 U.S.C. § 103(a).
9 "[A] showing that additional elements are obvious under 35 U.S.C. § 103
... is not by itself sufficient to establish that the additional elements are
well-understood, routine, conventional activities or elements to those in the
relevant field." (PTO Memorandum II, at 3 (citing MPEP § 2106.05 and
Berkheimer, 881 F.3d at 1369).)
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A preponderance of evidence of record fails to support the Examiner's
rejection of claims 1, 2, 4, and 19 under 35 U.S.C. § 101.
SUMMARY
We affirm the obviousness rejection and reverse the non-statutory
subject matter rejection.
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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