Ex Parte Foelling

Patent Trial and Appeal Board

Feb 26, 2019

13577951 (P.T.A.B. Feb. 26, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
13/577,951 08/09/2012
95683 7590 02/28/2019
Ley dig, Voit & Mayer, Ltd. (Frankfurt office)
Two Prudential Plaza, Suite 4900
180 North Stetson Avenue
Chicago, IL 60601-6731
FIRST NAMED INVENTOR
Jonas Foelling
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.
812956 4589
EXAMINER
LEE,SHUNK
ART UNIT PAPER NUMBER
2884
NOTIFICATION DATE DELIVERY MODE
02/28/2019 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):
chgpatent@leydig.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte JONAS FOELLING
Appeal 2018-006811
Application 13/577 ,951
Technology Center 2800
Before ADRIENE LEPIANE HANLON, N. WHITNEY WILSON, and
JEFFREY R. SNAY, Administrative Patent Judges.
SNAY, Administrative Patent Judge.
DECISION ON APPEAL 1
Appellant2 appeals under 35 U.S.C. § 134(a) from the Examiner's
decision rejecting claims 12-15 and 17-24. We have jurisdiction under
35 U.S.C. § 6(b).
We reverse.
1 We refer to the Specification ("Spec.") filed August 9, 2012; Final Office
Action ("Final Act.") dated October 2, 2017; Appellant's Appeal Brief
("App. Br.") filed February 16, 2018; Examiner's Answer ("Ans.") dated
April 19, 2018; and Appellant's Reply Brief ("Reply Br.") dated June 19,
2018.
2 Appellant identifies Leica Microsystems CMS GmbH as the real party in
interest. App. Br. 1.
Appeal 2018-006811
Application 13/577,951
BACKGROUND
The subject matter of the application on appeal relates to fluorescence
localization microscopy. Spec. ,r,r 8-9. According to the Specification,
enhanced resolution fluorescent images of a sample may be obtained by
stochastic localization, in which partial sample images are taken under
conditions in which only a fraction of dye particles are placed in an active
state-i.e., a state in which the particles may be excited to fluoresce. Id. ,r
3--4. For each partial image, light spots having a light characteristic greater
than a predetermined threshold are identified as events-i.e., a fluorescing
particle. Id. ,r 8. Events separately identified in the partial images are
combined to provide a complete sample image. Id. The Specification
describes a process and apparatus for performing fluorescence localization
microscopy in which the threshold applied to a partial localization image is
varied at least once prior to identifying events. Id. ,r,r 9, 11. Claim 12
reads:
Claim 12: A method for setting and using a suitable
evaluation parameter for stochastic localization microscopy
imaging with a fluorescence microscope, the evaluation
parameter being useable to prepare for generation of a complete
localization
microscopy image, the method comprising:
prior to generating a complete localization microscopy
image;
exciting fluorescent dye particles in a sample to
fluoresce;
detecting fluorescent light originating from the
fluorescent dye particles;
determining, for a first one of a plurality of partial
images taken during the detecting of the fluorescent light,
a graphical representation of a distribution of the
fluorescent light that is representative of a distribution of
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Appeal 2018-006811
Application 13/577,951
a light quantity on a detector of the fluorescence
microscope;
generating a signal representative of the graphical
representation of the light distribution;
displaying the graphical representation of the light
distribution on a display unit based on the generated signal;
associating each of a plurality of subregions of the
graphical representation of the light distribution with a
respective comparison value that is representative of a light
quantity in the respective subregion;
using a predefined threshold value as an evaluation
parameter during taking of the partial images which are later
used to form the complete localization microscopy image;
comparing the comparison values to the threshold value;
marking subregions having a comparison value that is
greater than the threshold value on the display unit with
predefined markings;
changing the threshold value in accordance with a user
input while the partial images continue to be taken, the
threshold value being changed prior to defining an event and
prior to determining a point representative of the event;
comparing the comparison values to the changed
threshold value after the user input;
defining subregions having a comparison value that is
greater than the changed threshold value as events and
excluding from evaluation subregions having a comparison
value that is lower than the changed threshold value;
determining, for each of the defined events, a point
representative of a position of the respective fluorescent dye
particle that caused the event; and then
generating the complete localization microscopy image
of the sample using the partial images based on the points of the
defined events.
App. Br. 11-12 (Claims Appendix) (emphasis added to highlight a key
recitation in dispute). Claim 22 is directed to an apparatus configured to
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Appeal 2018-006811
Application 13/577,951
perform the method of claim 12. Each remaining claim on appeal depends
from claim 12 or 22.
REJECTIONS
I. Claims 12, 14, 15, and 17-24 stand rejected under 35 U.S.C. § I03(a)
as unpatentable over Egner3 and Cummings. 4
II. Claim 13 stands rejected under 35 U.S.C. § I03(a) as unpatentable
over Egner, Cummings, and Lee. 5
OPINION
The Examiner finds Egner discloses a stochastic localization
microscopy method which includes, inter alia, exciting and detecting
fluorescent dye particles in a sample, displaying a graphical representation
of the fluorescing particles, and evaluating the graphical representation using
a predefined threshold. Final Act. 3--4. With regard to Egner's use of a
predefined threshold, the Examiner finds Egner discloses use of a so-called
CLEAN algorithm which, the Examiner finds, involves comparing a
detected light quantity with a predetermined threshold value. Id. at 4 ( citing
Egner 3286, 3289). The Examiner finds Egner discloses changing the
threshold value used in the CLEAN algorithm according to a user input to
tune resolution of the final image. Id. (citing Egner 3285, 3288, 3289).
3 Alexander Egner et al., Fluorescence Nanoscopy in Whole Cells by
Asynchronous Localization of Photoswitching Emitters, 93 Biophysical J.
3285-90 (2007).
4 US 2007/0081078 Al, published April 12, 2007.
5 US 2005/0232488 Al, published October 20, 2005.
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Application 13/577,951
Appellant argues, inter alia, that Egner fails to disclose changing the
threshold value in accordance with a user input while the partial images
continue to be taken prior to defining an event and prior to determining a
point representative of the event. App. Br. 4--5. Appellant argues that
Egner' s disclosed CLEAN algorithm merely applies a single threshold value
to determine whether all identified events have values greater than the
threshold. Id. at 7. Appellant argues that Egner's change in threshold relied
upon by the Examiner occurs only after all events are identified and
localized, as a means to tune resolution by excluding some data. Id.
Appellant's arguments are persuasive of reversible error. Egner's
CLEAN algorithm is depicted in Egner's Figure 2, which we reproduce
below.
start
+ ! smooth I
find max,mum pixel
I ,focilrd !
I
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Appeal 2018-006811
Application 13/577,951
(Figure 2 is a flow chart showing a combined CLEAN/mask-fitting
algorithm used to identify and localize single emitters in individual camera
frames. Egner 3286.)
Egner explains that the algorithm is applied to determine the planar
positions of fluorophores in a sparsely activated sample. Id. Egner further
explains that, pursuant to the algorithm, a pixel having the highest photon
count is identified and compared with a threshold value. Id. If the threshold
value is exceeded, the process is stopped. Id. If not, the pixel is localized,
and the algorithm scales the image to exclude the previously identified pixel
and identifies a next pixel having the highest photon count, comparing that
pixel's photon count with the threshold value, until a pixel is identified that
exceeds the threshold. Id. As such, Egner's singular threshold value serves
as an escape point from the algorithm. Id.
Regarding the claimed step of changing the threshold value, the
Examiner principally relies on Egner's teaching at page 3289. Final Act. 4.
There, Egner explains that applying a higher threshold "would improve the
resolution further but reduce the dynamic range." Egner 3289. The
Examiner does not provide an explanation as to why Egner' s teaching
regarding the effect of chosen threshold to be used in the disclosed algorithm
would result in the claimed changing of threshold while partial images are
taken, and prior to defining and localizing an event. In short, the Examiner
appears to equate selection of a threshold value to be used throughout
Egner's CLEAN algorithm with changing that threshold value during
application of the algorithm. Absent further findings or explanation, we are
persuaded of reversible error in that regard.
The Examiner presents a different rationale in the Answer. There, the
Examiner points to Egner' s disclosure that the density of fluorescing
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Application 13/577,951
molecules can be adjusted by changing excitation intensity, applying
auxiliary activation light, or prebleaching some of the molecules. Ans. 2-3
( citing Egner 3288). The Examiner reasons that changing the excitation
illumination would result in a change in resulting background noise which,
in tum, might require a change in threshold value used in Egner' s CLEAN
algorithm. Id. at 3. Appellant persuasively argues that the Examiner's new
rationale is not substantiated by the teachings of Egner. Reply Br. 2. The
Examiner does not direct us to evidence sufficient to support a finding that
Egner teaches or suggests altering the CLEAN algorithm threshold in
response to altering the applied excitation illumination. Nor does the
Examiner explain how selecting a different excitation illumination would
lead to changing the algorithm's threshold value during excitation.
The Examiner does not point to anything in Cummings or Lee that
addresses or cures the deficiencies in Egner.
For the foregoing reasons, the rejections are not sustained.
DECISION
The Examiner's decision rejecting claims 12-15 and 17-24 is
reversed.
REVERSED
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