Ex Parte Doyle et al

Board of Patent Appeals and Interferences

Jun 8, 2009

09916709 (B.P.A.I. Jun. 8, 2009)

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.
09/916,709 07/27/2001 Michael D. Doyle 001-1 8247
30080 7590 06/09/2009
LAW OFFICE OF CHARLES E. KRUEGER
P.O. BOX 5607
WALNUT CREEK, CA 94596-1607
EXAMINER
SMITH, CAROLYN L
ART UNIT PAPER NUMBER
1631
MAIL DATE DELIVERY MODE
06/09/2009 PAPER
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.
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte MICHAEL D. DOYLE, MAURICE J. PESCITELLI JR., BETSEY
S. WILLIAMS and GEORGE S. MICHAELS
__________

Appeal 2008-005145
Application 09/916,709
Technology Center 1600
__________

Decided:1 June 9, 2009
__________

Before ERIC GRIMES, RICHARD M. LEBOVITZ, and JEFFREY N.
FREDMAN, Administrative Patent Judges.

GRIMES, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a method
of combining image data and biological data from the same tissue sample.

1 The two-month time period for filing an appeal or commencing a civil
action, as recited in 37 C.F.R. § 1.304, begins to run from the decided date
shown on this page of the decision. The time period does not run from the
Mail Date (paper delivery) or Notification Date (electronic delivery).
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The Examiner has rejected the claims as indefinite and obvious. We have
jurisdiction under 35 U.S.C. § 6(b). We reverse both rejections.
STATEMENT OF THE CASE
The Specification discloses a process referred to as “spatial genomics”
that fulfills “a need to correlate gene expression data with morphological
structure in a useful and easy to understand manner, such as in a volume
visualization environment” (Spec. 6, ¶¶ 23, 25).
The Specification describes an example of the disclosed process, in
which a tissue sample is cut into histological thin sections, “producing two
sets of alternating serial sections” (id. at 7, ¶ 33). One set of sections is used
to generate image data via light microscopy (id.). The other set of sections
is used to generate gene expression data: a “UV laser . . . is used to incise a
grid pattern across each tissue section of the [second] set” and “each incised
section sample from each grid location of each section . . . [is transferred] to
a uniquely-coded isolation tube for lysis and further processing” for cDNA
microarray analysis (id. at ¶¶ 35-39).
“The gene expression data . . . are then spatially mapped onto the
original multidimensional morphological matrix of image data . . . [by]
superimpos[ing] the expression message distribution upon the morphological
volume image data” (id. at 8, ¶ 41).
Claims 1-4, 6, 7, and 9-11 are pending and on appeal. Claim 1 is
representative and reads as follows:
1. A method for creating a multidimensional morphological
reconstruction of biological data characterizing a biological tissue
comprising the steps of:
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cutting histologically thin sections of said biological tissue to
produce first and second sets of alternating serial sections of said
biological tissue;
mapping image data obtained from the first set of alternating
serial sections onto a tissue space coordinate system to construct a
multidimensional morphological tissue space matrix of image data of
the first set of alternating serial sections;
unattendedly micro dissecting each serial section in the second
set of alternating serial sections into a set of micro dissected section
samples;
assigning a unique code to each micro dissected section sample
micro dissected from the second set of alternating serial sections to
form a set of coded micro dissected section samples, with each unique
code indicating tissue space coordinates of each coded micro
dissected section sample in the morphological tissue space matrix;
analyzing each coded micro dissected section sample to obtain
biological data providing information on a plurality of biological
characteristics of the coded micro dissected section sample; and
spatially mapping the biological data characterizing each coded
micro dissected section sample, micro dissected from the second set
of alternating serial sections, onto the multidimensional
morphological tissue space matrix, constructed from the first set of
alternating serial sections and superimposing the biological data of the
coded micro dissected section sample upon volume image data
indicated by the code assigned to the coded micro dissected section
sample.

The claims stand rejected as follows:
• Claims 1-4, 6, 7, and 9-11 under 35 U.S.C. § 112, second
paragraph, as indefinite (Ans. 4);
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• Claims 1-3, 6, 7, and 9-11 under 35 U.S.C. § 103(a) as obvious in
view of Heppelmann,2 Cole,3 Farr,4 Emmert-Buck,5 and Lemelson6 (Ans. 5);
and
• Claim 4 under 35 U.S.C. § 103(a) as obvious in view of
Heppelmann, Cole, Farr, Emmert-Buck, Lemelson, and Bogen7 (Ans. 13).
DEFINITENESS
Issue
The Examiner has rejected claims 1-4, 6, 7, and 9-11 on the basis that
the phrase “unattendedly micro dissecting” is indefinite (Ans. 4). The
Examiner concludes that “[i]t is unclear what Applicant means by this
phrase. It is unclear by what or by whom the micro dissecting is
unattended.” (Ans. 4).
Appellants contend that when the claim is read in light of the
Specification’s paragraph 35, it is clear that “unattendedly micro dissecting”
means “micro-dissection without any selection by an investigator” (Br. 5).

2 B. Heppelmann et al., Serial sectioning, electron microscopy, and three-
dimensional reconstruction of fine nerve fibres and other extended objects,
156 Journal of Microscopy 163-172 (1989)
3 Kristina A. Cole et al., The genetics of cancer—a 3D model, 21 Nature
Genetics supplement 38-41 (1999)
4 Farr et al., US 5,811,231, issued September 22, 1998
5 Michael R. Emmert-Buck et al., Laser Capture Microdissection, 274
Science 998-1001 (1996)
6 Lemelson, US 6,058,323, issued May 2, 2000
7 Bogen et al., US 6,281,004 B1, issued Aug. 28, 2001
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The issue with respect to this rejection is: Did the Examiner err in
concluding that the phrase “unattendedly micro dissecting” makes the scope
of the claims unclear?
Findings of Fact
1. The Specification states that, in laser capture microdissection, a
“UV laser is . . . used to perform cold ablation of thin lines of tissue, creating
an incision around a specific area of the tissue section” (Spec. 4, ¶ 16).
2. The Specification states that Cole used laser capture micro-
dissection “to study the cellular-level gene expression activity associated
with prostate cancer” by precisely excising “specific tumor cells within the
prostate gland for microarray analysis of expression activity” (id. at 4, ¶ 18).
3. The Specification states that Cole’s “study focused on only small
groups of specific tissue areas, since the microdissection approach requires a
skilled operator and is extremely exacting work” (id.).
4. In describing an example of the disclosed method, the
Specification states that a “UV laser of the type described in Cole . . . is used
to incise a grid pattern across each tissue section of . . . [one] set of
alternating sections. . . . This is done with the use of said UV laser adapted
to the application end of a microarray-creation robotic apparatus.” (Id. at 7-
8, ¶ 35.)
5. The Specification states that incising a grid pattern using a laser
adapted for use by a robotic apparatus “allows for unattended section
incising of a large number of specimens” (id.).
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Principles of Law
“The test for definiteness is whether one skilled in the art would
understand the bounds of the claim when read in light of the specification.”
Miles Laboratories Inc. v. Shandon Inc., 997 F.2d 870, 875 (Fed. Cir. 1993).
“A decision on whether a claim is invalid under § 112, 2d ¶, requires a
determination of whether those skilled in the art would understand what is
claimed when the claim is read in light of the specification.” Orthokinetics
Inc. v. Safety Travel Chairs Inc., 806 F.2d 1565, 1576 (Fed. Cir. 1986).
Analysis
The Specification states that a prior art study using laser capture
microdissection to precisely excise tumor cells from prostate tissue focused
on specific tissue areas because that approach requires a skilled operator.
The Specification also states that the same type of laser can be adapted to a
robotic apparatus and used to incise a grid pattern across a set of tissue
sections, and that the robotically operated laser allows for “unattended
section incising” of the tissue specimens.
In our view, when the claim language is viewed in light of the
Specification, it is clear that “unattendedly microdissecting” is intended to
distinguish the microdissecting step in the claimed process from a process
like that of Cole, where a human operator actively controls the movement of
a laser as it is microdissecting a sample.
The Specification provides an example of unattended microdissection:
a robotic apparatus programmed to move a laser across a sample in a grid
pattern. The claimed process is, of course, not limited to the example
provided in the Specification, but the example informs the analysis of what
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the claim means by “unattendedly micro dissecting.” Read in light of the
Specification, “unattendedly micro dissecting” would be understood to mean
microdissection carried out without real-time control by a human operator of
the microdissection pattern.
Conclusion of Law
The Examiner erred in concluding that the phrase “unattendedly micro
dissecting” makes the scope of the claims unclear.
OBVIOUSNESS
Issue
The Examiner has rejected claims 1-3, 6, 7, and 9-11 under 35 U.S.C.
§ 103(a) as obvious in view of Heppelmann, Cole, Farr, Emmert-Buck, and
Lemelson (Ans. 5). The Examiner finds that the limitation of “unattendedly
micro dissecting,” as recited in each of the independent claims on appeal, is
disclosed by Emmert-Buck, which “describe[s] automatic microdissection
without manual procedure and a laser applied to specific locations of the
film to procure specifically targeted cells that can then be transferred” (id. at
9).
The Examiner finds that the other limitations of the claimed method
are taught by the other references (id. at 5-10), and concludes that the
claimed method as a whole would have been obvious in view of the
combined teachings of the references (id. at 10-13).
Appellants contend that none of the references disclose some of the
claim limitations, including “unattendedly micro dissecting each serial
sample into a set of micro dissected section samples” (Br. 8).
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The issue with respect to this rejection is: Did the Examiner err in
concluding that the cited references taught or would have suggested the
claimed method, including the step of unattendedly micro dissecting each
section in a set of alternating serial sections?
Additional Findings of Fact
6. The Examiner finds that “Heppelmann et al. do not describe
unattendedly microdissecting” (Ans. 6).
7. The Examiner finds that “Cole et al. do not teach unattendedly
microdissecting” (id. at 8).
8. The Examiner finds that “Farr et al. do not teach unattendedly
microdissecting” (id. at 9).
9. The Examiner finds that “Emmert-Buck et al. describe automatic
microdissection without manual procedure and a laser applied to specific
locations of the film to procure specifically targeted cells that can then be
transferred (page 998, third column, first full paragraph and abstract, lines
5-9) which represents unattendedly microdissecting” (id.).
10. The Examiner does not rely on Lemelson for any disclosure of
unattended microdissection (id. at 9-10).
11. Emmert-Buck discloses that “[s]everal methods have been
reported for tissue microdissection to address the problems associated with
analysis of heterogeneous tissue. These include gross dissection from frozen
tissue blocks . . . and microdissection with manual tools” (Emmert-Buck
998, middle col.).
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12. Emmert-Buck states that “although manual microdissection can
achieve good precision, it is time-consuming, labor-intensive, and requires a
high degree of manual dexterity” (id.).
13. The abstract of Emmert-Buck reads as follows:
Laser capture microdissection (LCM) under direct microscopic
visualization permits rapid one-step procurement of selected
human cell populations from a section of complex,
heterogeneous tissue. In this technique, a transparent
thermoplastic film (ethylene vinyl acetate polymer [EVA]) is
applied to the surface of the tissue section on a standard glass
histopathology slide; a carbon dioxide laser pulse then
specifically activates the film above the cells of interest. Strong
focal adhesion allows selective procurement of the targeted
cells. Multiple examples of LCM transfer and tissue analysis,
including polymerase chain reaction amplification of DNA and
RNA, and enzyme recovery from transferred tissue are
demonstrated.
(Id. at 998.)
14. Emmert-Buck discloses that “LCM has several advantages over
current tissue microdissection approaches: It is simple, requires no moving
parts, involves no manual microdissection or manipulations, and enables
one-step transfers” (id. at 998, right col., first full paragraph).
15. Emmert-Buck discloses that, in LCM, a “[t]ransparent EVA
thermoplastic film is applied to the surface of a routine tissue section
mounted on a glass slide. The tissue-EVA film sandwich is viewed under a
microscope, and the cells of interest are positioned in the center of the field.”
(Id. at 998, legend to Fig. 1A.)
16. Emmert-Buck discloses that “a single region of tissue can be
transferred to the film, or alternatively, the operator may move the slide and
transfer multiple regions to the same film” (id. at 999, left col.).
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17. Emmert-Buck discloses that “an individual glomerulus can be
completely procured from a kidney tissue section in <10 s, and hundreds of
glomeruli can be procured by an individual LCM operator in 1 hour with
minimal effort” (id. at 999, left col. to middle col.).
18. Emmert-Buck discloses that “the LCM operator visualizes the
transfer and can thus verify the specificity of the procured material” (id. at
999, middle col.).
Principles of Law
“The test of obviousness vel non is statutory. It requires that one
compare the claim’s ‘subject matter as a whole’ with the prior art ‘to which
said subject matter pertains.’” In re Ochiai, 71 F.3d 1565, 1569 (Fed. Cir.
1995) (quoting 35 U.S.C. § 103).
A proper § 103 analysis requires “a searching comparison of the
claimed invention – including all its limitations – with the teaching of the
prior art.” Id. at 1572.
“In rejecting claims under 35 U.S.C. § 103, the examiner bears the
initial burden of presenting a prima facie case of obviousness.” In re
Rijckaert, 9 F.3d 1531, 1532 (Fed. Cir. 1993).
Analysis
The Examiner relies on Emmert-Buck for disclosure of the step of
“unattendedly micro dissecting” serial sections of a tissue sample. Emmert-
Buck, however, makes clear that the LCM method relies on an operator to
select specific regions of a tissue section for procurement. See FFs 15-18.
Emmert-Buck’s statement that LCM “involves no manual microdissection”
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(FF 14) is not to the contrary. It is clear from the context that Emmert-
Buck’s reference to “manual microdissection” means the previously reported
technique of “microdissection with manual tools” (FF 11), which had the
drawbacks that it was “time-consuming, labor-intensive, and require[d] a
high degree of manual dexterity” (FF 12).
Emmert-Buck does not disclose “unattendedly micro dissecting” a
tissue section and the Examiner has pointed to nothing in any of the other
references to make up for that deficiency. The Examiner therefore has not
established that the claimed method would have been prima facie obvious
based on the cited references.
The Examiner also rejected claim 4 under 35 U.S.C. § 103(a) based
on Heppelmann, Cole, Farr, Emmert-Buck, and Lemelson, further combined
with Bogen (Ans. 13). The Examiner cited Bogen, however, only for the
“coded tissue section sample holder, as stated in claim 4” (id. at 14). Claim
4 also includes the limitation of “unattendedly micro dissecting” a tissue
section. For the same reason discussed above, the Examiner has not
established that the method of claim 4 would have been prima facie obvious
based on the cited references.
Conclusion of Law
The Examiner erred in concluding that the cited references taught or
would have suggested the claimed method, including the step of
unattendedly micro dissecting each section in a set of alternating serial
sections.
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SUMMARY
We reverse the rejections of claims 1-4, 6, 7, and 9-11 under 35
U.S.C. § 112, second paragraph, and under 35 U.S.C. § 103(a).

REVERSED
lp

LAW OFFICE OF CHARLES E. KRUEGER
P.O. BOX 5607
WALNUT CREEK CA 94596-1607