Michelle S. Bradbury et al.

Patent Trials and Appeals Board

Dec 12, 2019

14588066 - (D) (P.T.A.B. Dec. 12, 2019)

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.
14/588,066 12/31/2014 Michelle S. Bradbury 2003080-0791 9649
24280 7590 12/12/2019
CHOATE, HALL & STEWART LLP
TWO INTERNATIONAL PLACE
BOSTON, MA 02110
EXAMINER
HOFFMAN, JOANNE M
ART UNIT PAPER NUMBER
3793
NOTIFICATION DATE DELIVERY MODE
12/12/2019 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):
jnease@choate.com
patentdocket@choate.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte MICHELLE S. BRADBURY, ULRICH WIESNER,
RICHARD J.C. MEESTER, SNEHAL G. PATEL,
NADEEM R. ABU-RUSTUM, and MOHAN PAULIAH
____________

Appeal 2018-008342
Application 14/588,066
Technology Center 3700
____________

Before JOHN C. KERINS, STEFAN STAICOVICI, and
GEORGE R. HOSKINS, Administrative Patent Judges.

STAICOVICI, Administrative Patent Judge.

DECISION ON APPEAL

STATEMENT OF THE CASE.
Appellant1 appeals under 35 U.S.C. § 134 from the Examiner’s
decision in the Non-Final Office Action (dated Oct. 18, 2017) rejecting

1 We use the word “Appellant” to refer to “applicant” as defined in 37
C.F.R. § 1.42. Cornell University, Memorial Sloan-Kettering Cancer
Center, and Quest Projects B.V. are identified as the real parties in interest in
Appellant’s Appeal Brief (filed Feb. 2, 2018, hereinafter “Appeal Br.”).
Appeal Br. 2.
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claims 1–9, 11–15, 23–30, and 41–51.2 We have jurisdiction over this
appeal under 35 U.S.C. § 6(b).

SUMMARY OF DECISION
We AFFIRM.

INVENTION
Appellant’s invention is directed to “methods for simultaneously
imaging, in real-time, different fluorescent sources within a subject.” Spec.
para. 7.
Claim 1, the sole independent claim, is representative of the claimed
invention and reads as follows:
1. A method for optical imaging of a region within a
subject, the method comprising:
(a) administering to the subject two or more different
probe species each comprising a fluorescent reporter;
(b) directing excitation light into the subject, thereby
exciting the fluorescent reporters;
(c) simultaneously directing, via a prism, fluorescent
light of different wavelengths having been emitted by the
fluorescent reporters of the probe species in the subject as a
result of excitation by the excitation light onto a plurality of
spatially-separated detectors, wherein the prism directs light
received through an optical lens onto the plurality of spatially-
separated detectors via at least three discrete optical pathways;
(d) simultaneously detecting the fluorescent light of
different wavelengths so as to discriminate between signals
corresponding to the detected fluorescent light received from
each probe species; and

2 Claims 16–22 and 31–40 are withdrawn and claim 10 is canceled.
Supplemental Appeal Brief 4–6, 8–11 (filed Feb. 20, 2018, hereinafter
“Supp. Appeal Br.”).
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(e) processing the signals corresponding to the detected
fluorescent light to provide at least one image of the region
within the subject.

REJECTIONS
I. The Examiner rejects claims 1–9, 11, 12, 14, 43, 44, 48, and 50
under 35 U.S.C. § 103 as being unpatentable over Weissleder,3
Hasson,4 and Edgar.5,6
II. The Examiner rejects claim 13 under 35 U.S.C. § 103 as being
unpatentable over Weissleder, Hasson, Edgar, and van der
Vorst.7
III. The Examiner rejects claim 15 under 35 U.S.C. § 103 as being
unpatentable over Weissleder, Hasson, Edgar, and Promet.8
IV. The Examiner rejects claims 23 and 28–30 under 35 U.S.C.
§ 103 as being unpatentable over Weissleder, Hasson, Edgar,
and MatLab.9

3 Weissleder et al., US 2003/0044353 A1, published Mar. 6, 2003.
4 Hasson, US 2009/0317806 A1, published Dec. 24, 2009.
5 Edgar, US 6,593,558 B1, issued July 15, 2003.
6 We note the Examiner’s inclusion of claim 10 as part of this rejection;
however, as claim 10 is canceled, the rejection of claim 10 is moot. See
Non-Final Act. 3, 5; Supp. Appeal Br. 4.
7 J.R. van der Vorst et al., Dose Optimization for Near-Infrared
Fluorescence Sentinel Lymph Node Mapping in Melanoma Patients, 168(1)
BRITISH JOURNAL OF DERMATOLOGY 93–98 (2013).
8 Promet, Prostate Cancer Molecular Oriented Detection and Treatment of
Minimum Residual Disease 1–20 (2008) (http://www.fp6-promet.net/6.html,
last visited November 27, 2019).
9 MatLab Image Processing Toolbox, User’s Guide.
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V. The Examiner rejects claim 24 under 35 U.S.C. § 103 as being
unpatentable over Weissleder, Hasson, Edgar, and
Herzenberg.10
VI. The Examiner rejects claims 25 and 26 under 35 U.S.C. § 103
as being unpatentable over Weissleder, Hasson, Edgar,
Herzenberg, and Baecker.11
VII. The Examiner rejects claim 27 under 35 U.S.C. § 103 as being
unpatentable over Weissleder, Hasson, Edgar, and Livak.12
VIII. The Examiner rejects claim 41 under 35 U.S.C. § 103 as being
unpatentable over Weissleder, Hasson, Edgar, and AWDEH.13
IX. The Examiner rejects claims 45 and 46 under 35 U.S.C. § 103
as being unpatentable over Weissleder, Hasson, Edgar,
Herzenberg, Baecker, and AWDEH.
X. The Examiner rejects claim 42 under 35 U.S.C. § 103 as being
unpatentable over Weissleder, Hasson, Edgar, and Tan.14
XI. The Examiner rejects claims 47 and 49 under 35 U.S.C. § 103
as being unpatentable over Weissleder, Hasson, Edgar, and
Scrogin.15

10 Herzenberg et al., US 2011/0282870 A1, published Nov. 17, 2011. We
note both Appellant and Examiner refer to this reference as “Herzenbert.”
See Non-Final Act. 10; Appeal Br. 6.
11 Baecker, Workshop: Image Processing and Analysis with ImageJ and MRI
Cell Image Analyzer, Montpellier RIO Imaging, Apr. 30, 2010.
12 Livak et al., US 2005/0255485 A1, published Nov. 17, 2005.
13 AWDEH, US 2012/0330129 A1, published Dec. 27, 2012. We note that
the Examiner refers to this reference as “AWDEN” and Appellant as
“Awden.” See Non-Final Act. 13; Appeal Br. 7.
14 Tan et al., US 2004/0067503 A1, published Apr. 8, 2004.
15 Scrogin et al., US 2005/0252062 A1, published Nov. 17, 2005
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XII. The Examiner rejects claim 51 under 35 U.S.C. § 103 as being
unpatentable over Weissleder, Hasson, Edgar, and Stern.16

ANALYSIS
Rejection I
Appellant does not present arguments for the patentability of claims
2–9, 11, 12, 14, 43, 44, 48, and 50 apart from claim 1. See Appeal Br. 8–18.
Therefore, in accordance with 37 C.F.R. § 41.37(c)(1)(iv), we select claim 1
as the representative claim to decide the appeal of the rejection of these
claims, with claims 2–9, 11, 12, 14, 43, 44, 48, and 50 standing or falling
with claim 1.
The Examiner finds Weissleder discloses most of the limitations of
independent claim 1 including, inter alia, administering to a patient two or
more different imaging probes having different fluorescent properties,
illuminating the patient to excite the different fluorescent molecules so as to
emit fluorescent light of different wavelengths, and simultaneously detecting
and processing the emitted fluorescent light of different wavelengths to form
an image. Non-Final Act. 3 (citing Weissleder, paras. 26, 117, 125, claim
40). The Examiner further finds that Weissleder fails to disclose
“simultaneously directing, via a prism, fluorescent light of different
wavelengths . . . onto a plurality of spatially-separated detectors,” wherein
“the prism directs light received through an optical lens onto the plurality of
spatially-separated detectors via at least three [discrete] optical pathways.”
Id. at 3–4.

16 Stern, US 6,545,264 B1, issued Apr. 8, 2003.
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Thus, although the Examiner acknowledges Weissleder discloses
filtering and grating (citing Weissleder, paragraph 119 (“spectral separation
with a series of bandpass filters, diffraction grating or other means”)), the
Examiner turns to Hasson to specifically disclose the use of a prism to
spectrally disperse detected fluorescent light to multiple detectors. Non-
Final Act. 3 (citing Hasson, para. 53). According to the Examiner, spectral
dispersion of the fluorescent light results in light of different wavelengths.
Id. The Examiner then determines that it would have been obvious to a
person of ordinary skill in the art to employ Hasson’s prism to disperse the
fluorescent light in Weissleder because “this would be just using a well-
known light dispersing or filtering component to separate light as [any of]
gratings, filters, or prism[s] can be used.” Id. at 4.
The Examiner further turns to Edgar to disclose a “prism [that] directs
light received through an optical lens onto . . . [a] plurality of spatially-
separated detectors via at least three [discrete] optical pathways.” Non-Final
Act. 4 (citing Edgar, col. 14, ll. 8–20). According to the Examiner, in Edgar,
“prisms are used to create three colored beams which go to different sensors
and have different optical paths.” Id. The Examiner concludes that it would
have been obvious to a person of ordinary skill in the art to provide the
different light paths of Edgar to the fluorescent light in Weissleder, as
modified by Hasson, because “this would be just using a well-known light
dispersing or filtering component to separate light as gratings, filters, or
prism[s] can be used where a dichroic prism is known to split light into RBG
and have different paths.” Id.
Appellant argues that “none of the art teaches or suggests [the] use of
the prism recited in step (c)” of claim 1. Appeal Br. 11; see also Reply Br.
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12–13.17 According to Appellant, “Weissleder describes that spectral
separation requires a series of filters or gratings” (see Appeal Br. 11–12
(citing Weissleder, para. 119); see also Reply Br. 13–14, 16); “the prism of
Hasson is limited to directing light in a single direction and not directing
light received through an optical lens onto a plurality of spatially-separated
detectors via at least three discrete optical pathways” (see Appeal Br. 13
(citing Hasson paras. 38, 39, Figs. 3, 4); see also Reply Br. 16); and Edgar’s
“three sensitive layers 304 (red sensitive layer), 306 (green sensitive layer),
308 (yellow sensitive layer) are in contact with one another and are not
‘spatially-separated’ as recited by the present claim[]” (see Appeal Br. 15
(citing Edgar, col. 5, ll. 11–12, Fig. 3); see also Reply Br. 18–19). Thus,
according to Appellant, the combination of Weissleder and Hasson “direct[s]
light traveling in a single path” and the combination of Weissleder and
Edgar “direct[s] light through lenses [plural] onto a [contacting] three-layer
sensing film.” Appeal Br. 14, 16.
We are not persuaded by Appellant’s arguments because “[n]on-
obviousness cannot be established by attacking references individually
where the rejection is based upon the teachings of a combination of
references. [Each reference] must be read, not in isolation, but for what it
fairly teaches in combination with the prior art as a whole.” See In re Merck
& Co., 800 F.2d 1091, 1097 (Fed. Cir. 1986). Here, the Examiner employs
Hasson to disclose using a light collecting element 408, i.e., a single lens
408, to capture fluorescent light, and via a prism, to spectrally disperse the
captured fluorescent light onto a plurality of detectors, as an alternative to
using a diffraction grating, such as Weissleder. Ans. 16 (citing Hasson,

17 Appellant’s Reply Brief, filed Aug. 22, 2018.
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paras. 23, 56).18 As such, “[t]he Hasson reference is not used to illustrate
that there is more than one optical path,” but rather to teach using a lens and
a prism to capture and direct fluorescent light onto multiple detectors. Id.
Hence, in the combination of Weissleder and Hasson, Weissleder’s
fluorescent light is captured using a single lens and is spectrally dispersed
onto a plurality of detectors via a prism, as taught by Hasson.
As for Edgar, we agree with the Examiner that “Edgar is used [sic] to
teach that light can be split into different pathways [having different optical
paths] and that a prism is used to separate light.” Ans. 17. We appreciate
that the luminance priority color film disclosed in Edgar’s Figure 3 includes
three sensitive layers that are in contact, and, thus, not “spatially separated.”
See Appeal Br. 16; see also Reply Br. 18–19. However, we note that the
Examiner does not rely on the embodiment described in Edgar’s Figure 3,
but rather, relies on Edgar’s disclosure of CCD cameras, in particular, “three
chip” CCD cameras. See Non-Final Act. 4 (citing Edgar, col. 14, ll. 8–20).
Appellant does not persuasively explain why “three chip” CCD cameras do
not include detectors that are “spatially-separated.”
Hence, in the combination of Weissleder, Hasson, and Edgar, the
fluorescent light of Weissleder is captured by a single lens and spectrally
dispersed using a prism, as taught by Hasson, into three different pathways
having three different optical paths via Edgar’s “three chip” CCD camera.
Moreover, as Weissleder discloses spectral separation of emitted fluorescent
light using diffraction gratings and Hasson discloses using either prisms or
diffraction gratings, the substitution of a prism for a diffraction grating is
nothing more than an obvious selection between indisputably known

18 Examiner’s Answer, dated June 26, 2018.
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alternatives and the application of routine technical skills. KSR Int’l Co. v.
Teleflex Inc., 550 U.S. 398, 417 (2007). We, thus, agree with the Examiner
that it would have been obvious for a person of ordinary skill in the art to
employ a prism, as taught by Hasson, rather than Weissleder’s diffraction
grating, as they are equivalent structures that perform a similar function,
namely, spectral separation/dispersion. See Non-Final Act. 4; see also Reply
Br. 26–29. Furthermore, as Weissleder specifically discloses the use of
CCD light detection/image recording systems (see Weissleder, paragraph
124), we also agree with the Examiner’s conclusion that it would have been
obvious to a skilled artisan to employ Edgar’s “three chip” CCD camera to
detect and record an image in the process of Weissleder, as modified by
Hasson, as such cameras “produce beautiful images.” See Non-Final Act. 4;
Ans. 18; see also Reply Br. 20, 27–28.
We also do not agree with Appellant’s assessment that a person of
ordinary skill in the art would not employ Edgar’s “three chip” CCD camera
because of Edgar’s teachings that such “imaging systems are bulky . . .
require a plurality of prisms, and are expensive because they require
specialized lenses.” Appeal Br. 17; see also Reply Br. 19–20. Although we
appreciate that Edgar discloses some disadvantages of “three chip” CCD
cameras, nonetheless, “a given course of action often has simultaneous
advantages and disadvantages, and this does not necessarily obviate
motivation to combine.” Medichem, S.A. v. Rolabo, S.L., 437 F.3d 1157,
1165 (Fed. Cir. 2006). “The fact that the motivating benefit comes at the
expense of another benefit, however, should not nullify its use as a basis to
modify the disclosure of one reference with the teachings of another.
Instead, the benefits, both lost and gained, should be weighed against one
another.” Winner Int’l Royalty Corp. v. Wang, 202 F.3d 1340, 1349 n.8
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(Fed. Cir. 2000). Moreover, “[t]hat a given combination would not be made
by businessmen for economic reasons does not mean that persons skilled in
the art would not make the combination because of some technological
incompatibility. Only the latter fact would be relevant.” In re Farrenkopf,
713 F.2d 714, 718 (Fed. Cir. 1983).
In this case, Edgar discloses that although “three chip” CCD cameras
have some disadvantages, such as cost and complexity, nonetheless, such
cameras provide the benefit of “produc[ing] beautiful images, and are almost
universally used for professional studio work.” Edgar, col. 14, ll. 22–24
(emphasis added). We, thus, agree with the Examiner that although “three
chip” CCD cameras “may have drawbacks, it does not take away from the
benefits.” Ans. 18. Appellant does not persuasively explain how the
disadvantages of increased cost and technical complexity would discourage
a person of ordinary skill in the art from making the combination of
Weissleder, Hasson, and Edgar, to attain the advantage of “produc[ing]
beautiful images . . . for professional studio work,” as taught by Edgar.
Edgar, col. 14, ll. 22–24. Moreover, Appellant’s assertion that Edgar’s
“three chip” CCD cameras lack the sensitivity required for clinical
applications (see Reply Br. 20 (citing Edgar, col. 14, ll. 28–29)) is
unsupported attorney argument, as Appellant does not explain why a clinical
application requires dim light, and cannot take the place of evidence in the
record. In re Geisler, 116 F.3d 1465, 1470 (Fed. Cir. 1997).
Appellant further argues that (1) “the optics in the fiber optic probes
of Hasson are small in shape and size”; (2) “Hasson is limited to directing
fluorescent light along the same optical path, and not in at least three
discrete directions”; and (3) “Hasson is limited to collecting a single
fluorescence signal from a single location unless a scanning approach is
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used.” Reply Br. 15–18. In regards to Edgar, Appellant further argues that
Edgar: (1) “is limited to a scanning technique and therefore fails to
simultaneously detect fluorescent light” and (2) “similar to Hasson,
describes light rays traveling in the same direction.” Id. at 20–21 (citing
Edgar, col. 11, ll. 51–57), 24–25. Thus, Appellant asserts that a skilled
artisan “would quickly realize that the ‘relatively small diameter collecting
element 408’ of Hasson . . . is not combinable with the ‘bulky’ ‘three chip’
sensors described by Edgar.” Id. at 28 (citing Hasson, paras. 23, 57).
Furthermore, Appellant contends that “Weissleder in combination with
Hasson and Edgar suggest that the signal(s) emitted by the probes of
Weissleder would be detected using the fiber optic probes of Hasson and the
three-layer sensing film of Edgar (and not the bulky three chip imaging
technology discouraged by Edgar).” Id. at 29.
We are not persuaded by such arguments as Appellant once more
attacks the teachings of Weissleder, Hasson, and Edgar individually,
whereas the rejection is based on a combination of Weissleder, Hasson, and
Edgar. The Examiner is not proposing to use the particular fiber optic
probes of Hasson, which direct fluorescent light along the same optical path
in a scanning mode. “The test for obviousness is not whether the features of
a secondary reference may be bodily incorporated into the structure of the
primary reference; nor is it 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) (internal citations omitted).
Here, we note that Weissleder specifically discloses simultaneously
detecting and processing emitted fluorescent light of different wavelengths
including spectral separation with a diffraction grating and using CCD
imaging systems. See Weissleder, paras. 26, 119, 124, 125. Hasson
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discloses using a lens to capture fluorescent light and either diffraction
gratings or prisms to spectrally disperse the captured fluorescent light to
multiple detectors. See Hasson, paras. 53, 56. Edgar discloses “three chip”
CCD cameras including a prism that splits light into different pathways
having different optical paths and three spatially-separated detectors to
receive each of the split light beams. See Edgar, col. 14, ll. 8–24. As such,
in the combination of Weissleder, Hasson, and Edgar, the Examiner employs
a lens and a prism, as taught by Hasson, and a “three chip” CCD camera
having a prism and spatially-separated detectors, as taught by Edgar, to
simultaneously capture Weissleder’s fluorescent light of different
wavelengths and to spectrally disperse the captured fluorescent light to three
spatially-separated detectors. See Non-Final Act. 4.
In conclusion, for the foregoing reasons, we sustain the rejection
under 35 U.S.C. § 103 of claim 1 as unpatentable over Weissleder, Hasson,
and Edgar. Claims 2–9, 11, 12, 14, 43, 44, 48, and 50 fall with claim 1.

Rejections II–XII
Appellant relies on the same arguments discussed supra. See Appeal
Br. 18–22. Therefore, for the same reasons discussed above, we also sustain
Rejections II through XII.

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CONCLUSION

Claim(s)
rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
1–9, 11, 12,
14, 43, 44, 48,
50
103 Weissleder,
Hasson, Edgar
1–9, 11,
12, 14,
43, 44,
48, 50

13 103 Weissleder,
Hasson, Edgar, van
der Vorst
13
15 103 Weissleder,
Hasson, Edgar,
Promet
15
23, 28–30 103 Weissleder,
Hasson, Edgar,
MatLab
23, 28–30
24 103 Weissleder,
Hasson, Edgar,
Herzenberg
24
25, 26 103 Weissleder,
Hasson, Edgar,
Herzenberg,
Baecker
25, 26
27 103 Weissleder,
Hasson, Edgar,
Livak
27
41 103 Weissleder,
Hasson, Edgar,
AWDEH
41
45, 46 103 Weissleder,
Hasson, Edgar,
Herzenberg,
Baecker, AWDEH
45, 46
42 103 Weissleder,
Hasson, Edgar, Tan
42
47, 49 103 Weissleder,
Hasson, Edgar,
Scrogin
47, 49
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Claim(s)
rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
51 103 Weissleder,
Hasson, Edgar,
Stern
51
Overall
Outcome
1–9, 11–
15, 23–
30, 41–51

No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(1)(iv).

AFFIRMED