Ex Parte Kuypers et al

Patent Trial and Appeal Board

Sep 13, 2018

13224064 (P.T.A.B. Sep. 13, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
13/224,064 09/01/2011
34051 7590
Stevens Law Group
1754 Technology Drive
Suite #226
San Jose, CA 95110
09/17/2018
FIRST NAMED INVENTOR
Franciscus Albertus Kuypers
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.
CHOR-00601 8684
EXAMINER
DINES, KARLA A
ART UNIT PAPER NUMBER
1639
NOTIFICATION DATE DELIVERY MODE
09/17/2018 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):
uspto@stevenslawgroup.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte FRANCISCUS ALBERTUS KUYPERS,
WON CHUL LEE, and ALBERT P. PISANO 1
Appeal2017-008679
Application 13/224,064
Technology Center 1600
Before ERIC B. GRIMES, RYAN H. FLAX, and DAVID COTTA,
Administrative Patent Judges.
GRIMES, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to an
apparatus for analyzing the composition of individual cells, which have been
rejected as obvious. We have jurisdiction under 35 U.S.C. § 6(b ).
We reverse.
STATEMENT OF THE CASE
Appellants' "invention relates to apparatus and methods for analyzing
cytoplasmic components of single cells in large heterogeneous cell
populations." Spec. ,r 2. "Single-cell analysis is ... an important tool in
1 Appellants identify the Real Party in Interest as Children's Hospital &
Research Center Oakland. Appeal Br. 1.
Appeal2017-008679
Application 13/224,064
biology." Id. ,r 5. "Current techniques ... are mainly used to define cell
surface markers. Few probes are available that penetrate the plasma
membrane and allow measurement of cytoplasmic components in single
cells." Id.
The Specification describes an apparatus "for analyzing cytoplasmic
components of single cells in large, heterogeneous cell populations." Id.
,r 30. The apparatus includes an array of open microwells disposed on a
deposition plate, and a cover plate that covers the deposition plate to form
isolated microchambers that correspond to each of the micro wells. Id.
,r,r 30-31. The array also includes a pair of electrodes associated with each
of the microchambers, so that an electric field generated by the electrodes
lyses a cell in the microchamber to facilitate analysis of its cytoplasmic
components. Id. ,r 31.
Claims 1-23 are on appeal. Claim 1 is illustrative and reads as
follows ( emphasis added):
1. An apparatus for analyzing individual cell
composition in a heterogeneous cell population, the apparatus
compnsmg:
a deposition plate having an array of micro wells disposed
therein;
a cover plate overlying the deposition plate and sealing
the microwells of the array of microwells from one another and
sealing the microwells of the array of microwells, the cover
plate having a planar lower surface, each micro well of the array
of micro wells and a portion of the planar lower surface over the
each microwell defining a sealed volume; and
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Application 13/224,064
a pair of electrodes associated with at least one microwell
in the deposition plate and configured to generate an electric
field within the at least one microwell, the pair of electrodes
being formed on the portion of the planar lower surface over the
at least one microwell.
Claim 12, the only other independent claim, is directed to a method
that includes, among other steps, covering a deposition plate with a cover
plate that "isolat[ es] a single cell in at least one microwell, the cover plate
effective to seal the microwells of the array of micro wells with respect to
one another."
DISCUSSION
The Examiner has rejected the claims as follows:
Claims 1-11 under 35 U.S.C. § I03(a) as obvious based on
Deuthsch,2 Jackman, 3 and Fuller4 (Ans. 3);
Claims 12-22 under 35 U.S.C. § I03(a) as obvious based on
Deuthsch, Jackman, Fuller, and Brown5 (Ans. 8); and
Claim 23 under 35 U.S.C. § I03(a) as obvious based on Deuthsch,
Jackman, Fuller, Brown, and Albritton6 (Ans. 15).
The same issue is dispositive for all of the rejections.
The Examiner finds that Deuthsch discloses a device meeting most of
the limitations of claim 1 but does not teach a cover plate over each
2 US 2005/0014201 Al, published Jan. 20, 2005.
3 Rebecca J. Jackman, et al., Fabricating Large Arrays of Microwells with
Arbitrary Dimensions and Filling Them Using Discontinuous Dewetting, 70
ANAL. CHEM. 2280-2287 (1998).
4 US 2006/0216203 Al, published Sept. 28, 2006.
5 Robert B. Brown, et al., Current techniques for single-cell lysis, 5 J. R.
Soc. INTERFACE S131-SI38 (2008).
6 US 2004/0058423 Al, published Mar. 25, 2004.
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Application 13/224,064
microwell that defines a sealed volume or a pair of electrodes on the lower
surface of the cover plate over each of the micro wells. Ans. 4.
The Examiner finds that Jackman teaches "sealing arrays of
microwells using a cover slip in order to prevent evaporation" (id.) and
concludes that it would have been obvious "to modify the method and
system of Deutsch [sic] et al. with the use of a cover slip, sealing the wells,
as taught by Jackman et al., ... because Jackman et al. teaches an advantage
of sealing a microwell with a coverslip, to prevent evaporation" (id. at 6).
The Examiner finds that Fuller teaches that "integrated electrodes
placed in the cover plate over a microwell [were] known in the art at the
time of the instant invention." Id. at 4. The Examiner concludes that it
would have been obvious to modify the system made obvious by Deuthsch
and Jackman by "forming electrodes in the planar lower surface over the at
least one microwell, because Deuthsch already taught two microelectrodes
associated with one well" and "Fuller et al. teach electrodes placed in the
cover over a microwell [were] known in the art at the time of the instant
invention." Id. at 6-7.
Appellants argue, among other things, that "the approach of Jackman
is simply to create microwells filled with precise amounts of reagents and
prevent their evaporation." Appeal Br. 10. Appellants argue that, "in
Deutsch [sic], a closed bath or rinsing flow is used such that individual
sealing of microwells is not required to prevent drying due to evaporation.
There is therefore no rational basis to completely reconfigure Deuthsch to
solve a problem that does not exist and which would also eliminate the
function of the bath or rinsing flow." Id. at 10-11.
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Application 13/224,064
We agree with Appellants that the cited references do not support the
Examiner's conclusion that a skilled artisan would have considered it
obvious, based on Jackman, to modify Deuthsch's device to include a cover
plate that seals the microwells, including sealing them from one another.
Jackman states that "[t]echniques for handling and analyzing small
quantities of material are important for the development of new analytical
methods in both chemistry and biology." Jackman 2280, left col. "To
perform reactions on a small scale, methods are required to confine small
volumes of liquids spatially in what we will refer to as microreactors ( to
emphasize the focus on their use as containers for chemical reactions)." Id.
at 2280, right col. Jackman thus relates to methods of carrying out chemical
reactions using small quantities of liquids.
Jackman "present[s] a method that [it] refer[s] to as discontinuous
dewetting that addresses the major problem associated with working with
large arrays of wells: filling them uniformly and rapidly with a solution."
Id. at 2281, left col. Jackman states that "a problem associated with filling
the microreactors with pure, deionized water (and other, lower boiling
solvents) ... [is] the rapid ( <1 s) evaporation of the picoliter volumes under
ambient conditions." Id. at 2284, left col.
Jackman states that "[s]olutions to this problem have included the use
of high ionic strength, buffered, aqueous solutions (which may, in any event,
be necessary for biological experiments)." Id. Jackman states that it was
able to avoid the problem of evaporation, "for some applications, [by]
seal[ing] the arrays of wells with a microscope coverslip." Id. at 2284, right
col.
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Application 13/224,064
Deuthsch discloses "an Interactive Transparent Individual Cells
Biochip Processor (ITICBP) Device, for assessing a single, individual living
cell at [an] identifiable location." Deuthsch ,r 43. The device includes:
Id.
(a) a transparent cell chip (TCC) containing optically
transparent wells each ha[ ving] a bottom and it fits in size to
hold a single cell ... ; (b) means to direct the cells and force
them to enter into the wells, or to place them in the wells
directly, or to exit or remove them from the wells; ... ( d)
means to transfer solids, liquids, and cell suspensions to the
TCC; (e) means to transfer individual viable, and/or non-viable,
cells or group of cells or cell fragments; (f) means to measure
and assess ... changes that may occur as a result of presence or
absence of contact with other cells and/or particular
biologically-active materials.
Deuthsch discloses several embodiments of its device, some of which
are "designed to attract and/or repel the cells alternatively via controlled
delicate and localized Converging and Alternating Voltage (CAV)." Id.
,r 120. In one arrangement, CA Vis used to hold a cell in a well against the
force of gravity, and turning off the cell positioning electrode releases the
cells from the wells; " [ t ]he falling cells do not accumulate in the
interrogation regions since tangential rinsing is simultaneously performed."
Id. ,r 122, see also Fig. 39a. In another embodiment, "selectively operating
CA V ... yield[ s] selective drawing-out (repelling) forces on pre-selected
cells, opposing gravity .... Again, sweeping of cells out of the interrogation
region is carried out by means of tangential rinsing." Id. ,r 124, see also Fig.
39b.
Deuthsch also discloses an embodiment that does not include CA V or
tangential rinsing. Deuthsch states that
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Application 13/224,064
FIG. 44 depicts an upper view of a circular coin (30) encircled
by a bath (31), both surrounded by a belt wall (32) being a part
of a coin holder (33). The belt wall supports a transparent or
partially opaque plate (34) that can be a regular microscope
cover slip of a suitable size to cover the overall TCC surface
and has a height, which leaves under it a space, for maintaining
solutions.
Id. ,r 140. ("The 'coin' ... is the TCC's basic unit on which the array of
wells are located." Id. ,r 136.) "The examined sample of cells may be
exposed to various types of solutions and/or reagents and/or suspensions."
Id. ,I 141.
Thus, each of Deuthsch's embodiments includes an array of wells,
each containing a cell for examination, where the cells are exposed to an
external solution, either for tangential rinsing to remove cells from the
interrogation region or for exposing the examined cells to various types of
solutions or reagents.
We agree with Appellants that the cited references do not support the
Examiner's conclusion that it would have been obvious to a person of
ordinary skill in the art to modify Deuthsch's device to include a cover plate
that seals each of the microwells in its array, including sealing them from
one another. First, Jackman relates to a problem with evaporation that
occurs when filling large arrays of wells in a microreactor with pico liter
volumes of a lower boiling solvent. Jackman states that one solution to this
problem is to use the type of aqueous solutions that may be necessary in
biological experiments, like those of Deuthsch. The Examiner has not
provided evidence that Jackman's evaporation problem would be likely to
occur in Deuthsch's device.
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Appeal2017-008679
Application 13/224,064
In any event, Deuthsch's device is designed to expose cells in the
wells of a microarray to a surrounding solution. Therefore, there is no
reason to expect that evaporation would be a problem to be addressed and
sealing the wells to form separate, sealed volumes would be contrary to
Deuthsch's purpose of allowing cells to be released or expelled from the
wells, and removed by tangential rinsing, or to expose the examined cells to
solutions or reagents in an external solution.
Because the rejection based on Deuthsch, Jackman, and Fuller is not
supported by a preponderance of the evidence, we reverse the rejection of
claims 1-11 under 35 U.S.C. § 103(a).
The rejection of claims 12-22 based on Deuthsch, Jackman, Fuller,
and Brown, and the rejection of claim 23 based on Deuthsch, Jackman,
Fuller, Brown, and Albritton, are both based on the same rationale for
combining Deuthsch and Jackman. See Ans. 13, 15. The rejections of
claims 12-23 under 35 U.S.C. § 103(a) are therefore reversed for the reasons
discussed above.
SUMMARY
We reverse all of the rejections on appeal.
REVERSED
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