Ex Parte Leclerc

Patent Trial and Appeal Board

Mar 14, 2013

10202118 (P.T.A.B. Mar. 14, 2013)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte NORBERT LECLERC
__________

Appeal 2011-007529
Application 10/202,118
Technology Center 3700
__________

Before TONI R. SCHEINER, FRANCISCO C. PRATS,
and STEPHEN WALSH, Administrative Patent Judges.

SCHEINER, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 from the final rejection of
claims directed to a method for isolating a part of a biological layer. The
claims have been rejected as obvious. We have jurisdiction under 35 U.S.C.
§ 6(b).
STATEMENT OF THE CASE
Claims 1 and 5-8 are pending and on appeal. Claims 2-4 and 9-14
have been withdrawn from consideration.
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Claim 1 is representative of the subject matter on appeal:
1. A method for isolating a part of a layer of biological material,
comprising the steps of:
a) adhering the layer of biological material to one side of a
stabilization layer and applying the stabilization layer to a slide with the
biological material therebetween, wherein the stabilization layer surrounds
the biological material and is adhered along an edge to the slide for
protection of the biological material from contamination,
b) providing a substrate and applying a bonding layer to at least one
side of the substrate, and wherein the material of the bonding layer is a
material suitable for promoting adhesion between the stabilization layer and
the substrate;
c) bringing the side of the substrate with its bonding layer into contact
with the stabilization layer on the side of the stabilization layer facing away
from the layer of biological material;
d) with a focused laser beam describing a closed or substantially
closed curve at the layer of biological material to be isolated where it erodes
and excises only the biological material and the stabilization layer at the
described curve; and
e) then separating the substrate to which those excised portions of the
stabilization layer and of the biological material adhere by means of the
bonding layer.
Figures 1B-1D of the Specification are schematic representations of
an isolation method that meets the limitations of claim 1.
Figure 1B, reproduced below, generally depicts the arrangement of
layers resulting from steps a-c of claim 1:

As shown in Figure 1B, a biological material (tissue section 10) is
adhered to a stabilization layer (film 14), and the two layers are placed on a
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slide 18, with the tissue section 10 against the slide 18. Film 14 surrounds
the tissue section 10 and is itself fixed to the slide by an adhesive 16 (Spec.
¶ 45). Next, a composite layer comprising a substrate (adhesive tape 20) and
a bonding layer 22 (suitable for promoting adhesion between the substrate
and the film 14) is placed with the bonding layer against film 14 (id. at ¶ 46).
Figure 1C, reproduced below, depicts the result of step d of claim 1:

As depicted in Figure 1C, a tissue portion of interest is isolated using
the focused beam of a laser to describe a closed curve around the area of
interest, eroding only the tissue section 10 and the film 14 (id. at ¶ 47).
Figure 1D, reproduced below, depicts the result of step e of claim 1:

As depicted in Figure 1D, when adhesive tape 20 and bonding layer
22 are lifted away, the excised tissue piece 36 is lifted away as well, leaving
behind the remnant of film 14 and tissue section 10 which are still fixed to
the slide 18 by adhesive 16 (id. at ¶ 48).

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The Examiner relies on the following as evidence of obviousness:
Baer et al. WO 98/35215 Aug. 13, 1998
Lossing et al. US 2002/0132222 A1 Sep. 19, 2002
K. Schütze et al., Laser Micromanipulation Systems as Universal Tools in
Cellular and Molecular Biology and in Medicine, 44 CELL. MOL. BIOL. 735-
746 (1998).
The claims stand rejected under 35 U.S.C. § 103(a) as unpatentable
over Baer, Schütze, and Lossing.
ISSUE
The issue raised by this appeal whether the Examiner has established
that the specific series of steps, and the resultant configuration of materials
required by claim 1, would have been obvious over the combined teachings
of Baer, Schütze, and Lossing.
FINDINGS OF FACT
1. Baer teaches:
In laser capture microdissection, the operator looks
through a microscope at a tissue biopsy section mounted on a
standard glass histopathology slide, which typically contains
groups of different types of cells. A thermoplastic film is placed
over and in contact with the tissue biopsy section. Upon
identifying a group of cells of interest within the tissue section,
the operator centers them in a target area of the microscope
field and then generates a pulse from a laser . . . [which] causes
localized heating of the plastic film as it passes through it,
imparting to it an adhesive property. The cells then stick to the
localized adhesive area of the plastic tape directly above them,
whereupon the cells are immediately extracted and ready for
analysis.
(Baer 2: 1-11.)
2. Baer discloses a specialized cap and vessel for laser capture
microdissection (LCM) analysis. Specifically,
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[A]n aperture is disposed through the cap of an analysis vessel
. . . A thermoplastic lift-off substrate film is fastened across the
aperture by gluing . . . the thermoplastic around the periphery of
the aperture . . .The film itself acts as a transparent window that
allows for inspection of the lifted tissue sample.
[T]he cap and film assembly is placed in a suitable holder in the
laser capture microdissection apparatus and is aligned in contact
with the slide containing the tissue sample. The operator then
centers the cells of interest on the laser beam target and then
activates the laser pulse to weld the selected cell group to the
film.
After welding the tissue sample of interest to the film
affixed to the cap, a small volume of proteinase solution is
placed in the [analysis vessel], the cap is placed on the [vessel]
and the tube is inverted [and] [t]he tissue is dissolved[.]
(Baer 5: 1-15.)
3. Schütze discloses the laser microbeam microdissection LMM
technique in which a laser is used to “ablate[] a large, entirely material free
gap around the target cell [in a sample] to allow quick sample procurement
with a common metal needle” (Schütze 739, col. 2). “The needle was
carefully wiped over the isolated cell . . . the cell tightly adhered to the
needle and was transferred into the microfuge tube by simply cutting off the
needle tip” (id.).
4. Lossing teaches that non-specific transfer of sample material
during laser capture microdissection (LCM) can adversely affect analysis of
the sample. According to Lossing:
[W]hen Capsure™ devices[1] make contact with a tissue section
during LCM, the total working area of the Capsure ™ device

1 The CapSure™ device is similar to the specialized cap and analysis vessel
disclosed by Baer.
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touches the surface of the tissue section. Due to the friable
nature of tissue sections, loose material (whole cell or
macromolecular) is likely to adhere to the surface of the
Capsure™ device during LCM. This is known as non-specific
transfer. Since LCM sample recovery involves extraction of the
material on the surface of a Capsure ™ device, any non-specific
material transferred during LCM can cause sample
contamination and adversely affect the quality and accuracy of
downstream analyses.
(Lossing ¶ 6.)
5. Lossing teaches that the non-specific transfer of loosely adhered
tissue or cells during LCM can be reduced or eliminated by “applying a
protective barrier or coating to biological tissue sections prior to LCM, [so
that] loosely adhered tissue would be retained beneath the barrier, whereas
tissue targets adhered to the melted polymer would easily be removed with
the Capsure™ device” (Lossing ¶ 8).
DISCUSSION
The Examiner finds that Baer discloses “transporting [a] sample to a
cap (‘substrate’) by attaching a thermoplastic film (‘stabilization layer’) to
the cap (‘substrate’) using double sided tape (‘bonding layer’) and placing
the thermoplastic film (‘stabilization layer’) over a tissue sample on a slide”
(Ans. 3-4). The Examiner further finds that Schütze teaches “separating the
tissue of interest from the rest of the sample by cutting the tissue and the
overlying membrane with a laser” (id. at 4). Finally, the Examiner finds that
Lossing discloses “providing a covering to provide a barrier between the
sample and the surrounding environment” (id.).
The Examiner concludes that
It would have been obvious . . . to employ the laser cutting step
of Schütze . . . in the process of Baer . . . since this would
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assure that only the tissue of interest was sampled and would
allow the collection of non-circular portions of the tissue, to
configure the stabilization layer to surround the biological
material, since this would cause loosely adhered tissue to be
retained beneath the barrier; would improve visualization of the
sample and would stabilize and retard degradation of the
sample, as taught by Lossing[.]
(Id. at 4.)
Appellant contends, in relevant part, that “Baer does not teach step a)
. . . [or] step c) of claim 1 since in that step the bonding layer is placed on
the stabilization layer on the side facing away from the sample while the
stabilization layer is covering the sample” (App. Br. 6), “while in Baer the
sample is being welded to the [thermoplastic] liftoff film” (id.). Appellant
contends that step d, wherein a portion of the sample and a portion of the
stabilization layer are excised from the rest of the sample and stabilization
layer, is not taught by Baer either (id.).
Moreover, Appellant contends that Baer’s laser welding of the sample
to the thermoplastic film window in the cap of the analysis vessel “makes a
cutting step entirely superfluous” (id. at 7, 11), and “the Examiner fails to
address . . . how Baer would be benefitted by the cutting technique in
Schütze” (id. at 7). Appellant further contends that even if one were to
combine “the process according to Baer with the process of Schütze the
result is not the method of claim 1” (id.). Finally, Appellant contends that
“retrieving the step of lamination from the Lossing . . . reference and
‘plugging’ it into the Baer method does not result in the method as claimed”
(id. at 12).
We agree with Appellant that the Examiner has not adequately
explained how any possible combination of the references would result in
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the particular sequence of layers obtained according to steps a-c of claim 1
(i.e., slide, sample, stabilization layer adhered to both the sample and the
slide, bonding layer, and substrate, see e.g., Fig. 1B). Moreover, we agree
with Appellant that the Examiner has not provided an adequate reason why
one of ordinary skill in the art would have added a superfluous laser cutting
step (i.e., step d) to Baer’s laser capture microdissection technique, in which
a laser is used to melt a thermoplastic film above portions of the sample of
particular interest in order to adhere only those portions to the film, thereby
separating portions of interest from the rest of the sample.
CONCLUSION
The Examiner has not established that the specific steps, and the
resultant sequence of materials required by claim 1, would have been
obvious over the combined teachings of Baer, Schütze, and Lossing.
SUMMARY
The rejection of claims 1 and 5-8 under 35 U.S.C. § 103(a) as
unpatentable over Baer, Schütze, and Lossing is reversed.

REVERSED

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