WAYNE STATE UNIVERSITY

Patent Trials and Appeals Board

Jul 20, 2020

2019006879 (P.T.A.B. Jul. 20, 2020)

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.
15/067,901 03/11/2016 MATTHEW J. ALLEN WSU0231PUSP 1062
22045 7590 07/20/2020
Brooks Kushman
1000 Town Center
22nd Floor
Southfield, MI 48075
EXAMINER
PERREIRA, MELISSA JEAN
ART UNIT PAPER NUMBER
1618
NOTIFICATION DATE DELIVERY MODE
07/20/2020 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@brookskushman.com
kdilucia@brookskushman.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte MATTHEW J. ALLEN
__________

Appeal 2019-006879
Application1 15/067,901
Technology Center 1600
__________

Before ULRIKE W. JENKS, RACHEL H. TOWNSEND, and
MICHAEL A. VALEK, Administrative Patent Judges.

TOWNSEND, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims to a
method of magnetic resonance imaging a target tissue in a subject, which
have been rejected as obvious. We have jurisdiction under 35 U.S.C. § 6(b).
We affirm in part.
STATEMENT OF THE CASE
“Redox environments are critical to the homeostasis of living
organisms.” (Spec. ¶ 4.) “[C]onsiderable research effort has focused on
developing systems to measure changes in redox environment” because

1 We use the word “Appellant” to refer to “applicant” as defined in 37
C.F.R. § 1.42. Appellant identifies the real party in interest as Wayne State
University. (Appeal Br. 2.)
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“redox stress is associated with ailments” such as cancer and cardiovascular
disease. (Id.) The invention is directed to a method of magnetic resonance
imaging of target tissue based on reduction potentials of the imaging agent
and target tissue. (Id. ¶ 6.)
Claims 1–20 are on appeal. Claims 1 and 5 are representative and
reads as follows:
1. A method of magnetic resonance imaging a target
tissue in a subject, the method comprising:
a) administering a first Eu2+ -containing complex to the
subject, the first Eu2+-containing complex having a reduction
potential that is more negative than a reduction potential for a
selected compound present in the target tissue; and
b) taking a first set of images of the target tissue in the
subject by T1-weighted magnetic resonance imaging.
5. The method of claim 1 further comprising
c) administering a second Eu2+-containing complex to the
subject, the second Eu2+-containing complex having a reduction
potential that is more positive than a reduction potential for the
selected compound present; and
d) taking a second set of images of the target tissue in the
subject by T1-weighted magnetic resonance imaging.
(Appeal Br., Claims Appendix 1–2.)

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The prior art relied upon by the Examiner is:
Name Reference Date
Allen 2016/0022842 A1 Jan. 28, 2016
Whiteford 2009/0074833 A1 Mar. 19, 2009
K. Konstantinidis, Mechanisms of Cell Death in Heart Disease, 32(7)
Arterioscler. Throm. Vasc. Biol., 1–20 (2012) (author manuscript)

The following ground of rejection by the Examiner is before us on
review:2
Claims 1–20 under 35 U.S.C. § 103(a) as unpatentable over Allen,
Konstantinidis, and Whiteford.
DISCUSSION
The Examiner finds that Allen teaches “a method of magnetic
resonance imaging of an organ or organ structure in a subject comprising a
step of administering a liposome composition of Eu2+-complex, such as
compound 4[,] and providing images of the organ subject.” (Final Action 4.)
The complex comprising a multi-dentate ligand structure that “can be used
to tune the oxidation potential over a physiologically relevant range” and the
complexes “can be used for imaging redox-active disease states.” (Ans. 9.)
The Examiner finds that compound 4 is provided as a representative
example in a finite list of Eu2+-complex compositions in Figure 2 of Allen.
(Final Action 3; Ans. 9.) According to the Examiner “it would have been
obvious to use any one of the compounds in the finite list as a lead

2 The Examiner had also rejected claims 1–4 for non-statutory double
patenting. However, this rejection has been rendered moot by the filing on
June 19, 2019, and acceptance on June 20, 2019, of a terminal disclaimer
over the co-pending application that was the foundation for the non-statutory
double patenting rejection.
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compound and tailor the complexes for imaging redox-active disease states.”
(Ans. 9.)
Regarding the requirement of certain claims for a second Eu2+-
complex, the Examiner recognizes that such is not taught by Allen, but that
using a second such compound would have been obvious in light of the
teachings of Whiteford. (See, e.g., id.) The Examiner finds that “Whiteford
teaches of the administration (e.g., intravenous) of one or more metal
coordinated bridged polycyclic compounds (e.g., cryptands) that may be
used for MRI.” (Id.) According to the Examiner, the two Eu2+ complexes
“will have [two] different potentials, not excluding one that is more negative
and one that is more positive than a reduction potential for the selected
compound present in the target tissue.” (Id.) The Examiner finds that “it
would have been obvious to one of ordinary skill in the art to utilize multiple
Eu2+-containing complexes for MRI of redox-active disease states using the
chemistry of Eu” (id. at 11), “it would have been obvious to one of ordinary
skill in the art to provide images of each compound within a subject after
administration” (id. at 10), and “[i]t would have been predictable . . . to
compare different sets of MRI images and determine location and/or
concentration of the Eu2+-cryptand contrast agents as the examination and/or
comparison of MRI images by a physician is standard and customary” (id. at
9–10).
The Examiner relied on Konstantinidis only to address the dependent
claim limitation that the target tissue be necrotic tissue. (See Ans. 3.) The
Examiner notes that although “Allen does not disclose necrotic tissue,” it
does teach targets of interest include cardiovascular disease, and
Konstantinidis evidences that “major cardiac syndromes, myocardial
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infarction and heart failure cause cells to die primarily by apoptosis or
necrosis.” (Id. at 4.) According to the Examiner, “[t]herefore, it would have
been predictable that the examination of cardiovascular diseases includes the
imaging of necrotic tissue.” (Id.)
We address the claims requiring only one Eu2+-containing complex
separately from those claims requiring two such complexes.
Claims 1–4, 10, 17, 18
We address claim 1 from this group, because Appellant does not argue
the noted dependent claims separately. We agree with the Examiner that
claim 1 is obvious over the cited references. We, however, only rely on
Allen in arriving at this conclusion. In affirming a multiple-reference
rejection under 35 U.S.C. § 103, the Board may rely on fewer than all of the
references relied on by the Examiner in an obviousness rationale without
designating it as a new ground of rejection. In re Bush, 296 F.2d 491, 496
(CCPA 1961).
Allen teaches Eu2+-containing complexes that can be used for MRI
based on the redox chemistry of Eu. (Allen ¶¶ 5, 54.) Allen teaches that
there are “targets that cause changes in redox behavior” and “are associated
with cancer, inflammation, and cardiovascular disease.” (Id. ¶ 3.) Allen
provides redox potential for hypoxic squamous cell carcinoma of the neck,
hypoglycemic coma, and septic pathology as well as healthy blood and
hemoglobin. (Id., Fig. 2.) In addition, Allen provides six (6) specific Eu2+-
containing complexes and their redox potentials, some of which have a
redox potential that is more negative than septic pathology. (Id.) We agree
with the Examiner that “it would have been obvious to use any one of the
compounds in the finite list as a lead compound and tailor the complexes for
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imaging redox-active disease states.” (Ans. 9.) “Reading a list and selecting
a known compound to meet known requirements is no more ingenious than
selecting the last piece to put into the last opening in a jig-saw puzzle. It is
not invention.” Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S.
327, 335 (1945); see also Merck & Co. Inc. v. Biocraft Laboratories, Inc.,
874 F.2d 804, 807 (Fed. Cir. 1989). Thus, even though Allen may not
explicitly state selecting a first Eu2+-containing complex that has a redox
potential that is more negative than a redox potential for a selected
compound, (Appeal Br. 5), we conclude such a selection is nevertheless
suggested. “[T]he test of obviousness is not express suggestion of the
claimed invention in any or all of the references but rather what the
references taken collectively would suggest to those of ordinary skill in the
art presumed to be familiar with them.” In re Rosselet, 347 F.2d 847, 851
(CCPA 1965). That is “the 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’l Co. v. Teleflex Inc., 550
U.S. 398, 418 (2007). Selecting one of the exemplified compounds of Allen,
which is taught to have a more negative redox potential than a target of
sepsis pathology, for example, to use to image such pathology is implicitly
suggested.
Consequently, we affirm the Examiner’s rejection of claim 1 as being
obvious over Allen.
Appellant does not separately argue claims 2–4, 10, 17, 18, and
therefore they fall with claim 1. 37 C.F.R. § 41.37(c)(1)(iv).
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Claims 5–9, 11–16, 19, and 20
Despite the foregoing, we disagree with the Examiner that the claims
requiring two Eu2+-containing complexes, one of which has a redox potential
that is more negative than a redox potential for a selected compound, and the
other having redox potential that is more positive than a redox potential for a
selected compound 2 would have been obvious from the cited references.
As Appellant correctly observes, Whiteford has a very limited
disclosure relating to MRI, specifically it contains one sentence that states
“[a]mine functionalized cryptands are well known for . . . MRI imaging.”
(Appeal Br. 6; Whiteford ¶ 250.) As for Whiteford’s teachings regarding the
use of one or more bridged polycyclic based compounds (cryptands that bind
a metal) (Ans. 5), we note that it is not concerned with, nor does it suggest,
contrary to the Examiner’s assertion, use for MRI. Rather, the disclosure
regarding the use of more than one cryptand that binds a metal is directed to
such use for the control of bone resorption or in an antimicrobial coating.
(See, e.g., Whiteford, Abs., ¶¶ 14, 16, 47.) There is nothing in Whiteford
that would suggest using multiple Eu2+-containing complexes for imaging,
much less with the characteristics claimed.
Konstantinidis also does not provide any teaching that would suggest
this. Indeed, the Examiner asserts only that this reference “was used to teach
that major cardiac syndromes, myocardial infarction and heart failure cause
cells to die primarily by apoptosis or necrosis.” (Ans. 10.)
“[T]he examiner bears the initial burden, on review of the prior art or
on any other ground, of presenting a prima facie case of unpatentability.” In
re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992). We find that the
Examiner has not met the requisite burden. Consequently, we do not affirm
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the Examiner’s rejection of claims 5–9, 11–16, 19, and 20 as being obvious
over Allen, Konstantinidis, and Whiteford.

DECISION SUMMARY
In summary:
Claims
Rejected
35 U.S.C.
§
Reference(s)/Basis Affirmed Reversed
1–20 103 Allen,
Konstantinidis,
Whiteford
1–4, 10, 17,
18
5–9, 11–16,
19, 20

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). See 37 C.F.R.
§ 1.136(a)(1)(iv).

AFFIRMED-IN-PART