Ex Parte Ungrin et al

Patent Trials and Appeals Board

Apr 8, 2019

12528135 - (D) (P.T.A.B. Apr. 8, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
12/528, 135 11/12/2010
1059 7590 04/10/2019
BERESKIN & PARR LLP/S.E.N.C.R.L., s.r.l.
40 KING STREET WEST
40th Floor
TORONTO, ON MSH 3Y2
CANADA
FIRST NAMED INVENTOR
MarkUngrin
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.
7771-Pl314US01 1860
EXAMINER
SCHUBERG, LAURA J
ART UNIT PAPER NUMBER
1657
NOTIFICATION DATE DELIVERY MODE
04/10/2019 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):
ipprocessingcentre@bereskinparr.com
PTOL-90A (Rev. 04/07)
UNITED ST ATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte MARK UN GRIN and PETER ZANDSTRA
Appeal2018-006075
Application 12/528, 135
Technology Center 1600
Before JEFFREY N. FRED MAN, DEBORAH KATZ, and JOHN G. NEW,
Administrative Patent Judges.
FRED MAN, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeaP, 2 under 35 U.S.C. § 134(a) involving claims to a
method of forming cell aggregates. The Examiner rejected the claims as
indefmite and obvious. We have jurisdiction under 35 U.S. C. § 6(b ). We
affirm.
1 Appellants identify the Real Party in Interest as STEMCELL Technologies
Canada Inc. (see App. Br. 3).
2 We have considered and herein refer to the Specification of Aug. 21, 2009
("Spec."); Final Office Action of May 9, 2017 ("Final Act."); Appeal Brief
of Oct. 6, 2017 ("App. Br."); Examiner's Answer of Feb. 21, 2018 ("Ans.");
and Reply Brief of Apr. 23, 2018 ("Reply Br.").
Appeal 2018-006075
Application 12/528, 135
Statement of the Case
Background
"[CJ ell aggregates are used for the differentiation of pluripotent stem
cells such as embryonic stem cells, in the fields of developmental biology,
cellular therapies and regenerative medicine" (Spec. 1 :5-8). Prior methods
for producing human embryonic stem cell ("hESC") aggregates known as
Embryoid Bodies ("EBs") do not address "variables that impact the
reproducibility of EB formation (such as the shape and volume of the
aggregation wells)" or "the production of EBs from higher density plate
formats or arrays of microwells" (Spec. 2:2-5). "In addition, hESC cultured
using standard techniques do not consistently form high-quality aggregates
( aggregates are often loose, poorly defined and/ or cannot be recovered
intact) using these methods" (Spec. 2:8-10). "Therefore there is a need in
the art for a method to reproducibly and efficiently generate consistent cell
aggregates, such as stem cell aggregates or embryoid bodies from
mammalian embryonic stem cells" (Spec. 2:28-30).
The Claims
Claims 82, 85, 87-92, 94, 97, 100, and 103-111 are on appeal.
Independent claim 82 is representative and reads as follows:
82. A method for forming multiple cell aggregates within a
well of a well plate, comprising:
a) depositing a plurality of cells into a volume of at least
one of a plurality of wells in a well plate, the volume of the one
well being at least partially bounded by a base having a
plurality of microwells in communication with the well volume,
each microwell extends along a microwell axis from an upper
plane to a bottom and having a microwell depth of less than
500µm in the axial direction, each microwell also comprises
one or more sidewalls that converge to a point at the bottom of
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Application 12/528, 135
the microwell to urge cells deposited in the microwell to
contact each other in the presence of a force urging the cells in
the micro well towards the bottom of the micro well;
b) conveying the plurality of cells from the volume into
at least a portion of the plurality of microwells whereby a
portion of the plurality of cells is collected and concentrated
within each of the at least a portion of the plurality of
microwells;
c) incubating the portion of the plurality cells within each
of the at least a portion of the plurality of the microwells to
form a respective cell aggregate within each of the at least a
portion of the plurality of microwells, whereby a plurality of
cell aggregates are formed within the one well.
The Rejections
A. TheExaminerhasrejectedclaim 111 under 35U.S.C. § 112,
second paragraph, as being indefmite (Final Act. 3).
B. The Examiner has rejected claims 82, 85, 88, 94, 97, 105, and 108
under 35 U.S.C. § 103(a) as obvious over Penick, 3 Ravkin, 4 and
Palecek5 (Final Act. 5-10).
C. The Examiner has rejected claims 87 and 89-91 under35 U.S.C.
§ 103(a) as obvious over Penick, Ravkin, Palecek, andDeutsch6
(Final Act. 10-11 ).
3 Penick et al., High-throughput aggregate culture system to assess the
chondrogenic potential of mesenchymalstem cells, 39 BioTechniques 687-
691 (2005).
4 Ravkin et al., US 2006/0013031 Al, published Jan. 19, 2006.
5 Palecek et al., US 2008/0026460 Al, published Jan. 31, 2008.
6 Deutsch et al., US 2005/0064524 Al, published Mar. 24, 2005.
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Application 12/528, 135
D. The Examiner has rejected claims 92, 103, 104, and 106 under 35
U.S.C. § 103(a) as obvious over Penick, Ravkin, Palecek, and
Morgan7 (Final Act. 11-14).
E. The Examiner has rejected claims 94 and 97 under 35 U.S. C.
§ 103(a) as obvious over Penick, Ravkin, Palecek, and Watanabe 8
(Final Act. 14--15).
F. The Examiner has rejected claim 100 under 35 U.S.C. § 103(a) as
obvious over Penick, Ravkin, Palecek, and Cruz 9 (Final Act. 16-
17).
G. The Examiner has rejected claims 107, 109, 110, and 111 under 3 5
U.S.C. § 103(a) as obvious over Penick, Ravkin, Palecek, and
Oldenburg10 (Final Act. 17-18).
A. 35 USC§ 112, second paragraph, indefiniteness
The Examiner determines that claim 111, depending from claim 110,
is indefmite for reciting "wherein each microwell has a width of about 400
microns" (Final Act. 3). The Examiner states that "it is unclear how a
microwell with an inverted, frusto-pyramidalconfiguration would have a
single width defming it. It is unclear if this width is referring to the opening
of the micro well, the bottom of the micro well or along the pyramid sides of
the microwell" (Final Act. 3--4).
7 Morgan et al., WO 2007/087402 A2, published Aug. 2, 2007.
8 Watanabe et al., A ROCK inhibitor permits survival of dissociated human
embryonic stem cells, 25 Nature Biotechnology 681---686 (2007).
9 Cruz, WO 2006/024966 A2, published Mar. 9, 2006.
10 Oldenburg et al., US 6,027,695, issued Feb. 22, 2000.
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Application 12/528, 135
Appellants submitted an amendment to claim 111 in the Appeal Brief
"to clarify that each microwell has a width at the upper plane" (see App. Br.
9, 46). The Examiner did not enter the after-fmal amendment (Ans. 3, see
37 C.F.R. § 41.33(b)).
Because the amendment has not yet been entered, the claim language
remains indefmite. We therefore affrrm the Examiner's indefmiteness
rejection.
B.-G. 35 USC§ 103(a)
Because these rejections rely on the combination of Penick, Ravkin
and Palecek, along with other references, we will consider them together.
The Examiner fmds Penick teaches a method of seeding stem cells
into the wells of a V Bottom microplate, centrifuging, and incubating until
the cells form high-density aggregates (see Final Act. 6-7). The Examiner
fmds "Penick discloses the advantages ofv bottom microplates where the
sidewalls of the micro wells converge toward each other in the shape of a v
(thus v bottom)" (Ans. 7). More specifically, the Examiner fmds "Penick[]
describes wherein the v-bottom microplates are chosen because they allow
cell-cell interaction as compared to microplates that had wells with wide
angle bottoms" (Ans. 9-10). The Examiner fmds that Penick does "not
teach wherein the microplate is located at the bottom of a well in a
microdevice" (Final Act. 8).
The Examiner fmds that Rav kin teaches a microwell device
containing wells with each well containing subwells (Final Act. 8). The
Examiner fmds that Rav kin teaches "[ t ]he subwells of a well also may have
any suitable shape or size (page 3 para 42) and disclose subwells with
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sidewalls that are frustoconical ( extend inwardly) (para 97, Figure 6C)" (id.).
The Examiner determines that:
One of ordinary skill in the art would have been motivated to
use the microwell device of Rav kin et al. with subwells in av-
bottom shape in the in vitro testing method of Penick et al.
because Ravkin et al. teach that their device provides numerous
advantages over standard microplates and Penick et al. teach
that it is desirable to improve the efficiency of the in vitro
testing of their cell aggregates for the examination of multiple
variables
(Final Act. 9). The Examiner acknowledges that Penick and Ravkin "are
silent with regard to the depth and width of the microwells" (id.).
The Examiner finds Palecek teaches "methods for culturing stem cells
in micro wells ... for the harvesting of aggregates of uniform size" (Final
Act. 9). The Examiner fmds Palecek teaches "[t]hemicrowells can have a
depth between 10 microns and about 1000 microns and lateral dimensions
(length and width) between about 50 microns and about 1000 microns on a
side and alternatively can be between about 100 microns and 500 microns on
a side" (id.). The Examiner determines a person of ordinary skill in the art
would have been motivated to apply the microwell dimensions of Palecek in
combination with Penick and Ravkin, "because Palecek suggests ranges that
includes these dimensions are suitable for microwells used for culturing
stem cells and forming aggregates for harvest" (Final Act. 10).
The issue with respect to this rejection is: Does a preponderance of
the evidence of record support the Examiner's conclusion that claim 82
would have been obvious?
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Findings of Fact ("FF'')
1. Appellants' Specification teaches "[i]n one embodiment, the
device is a microwell device with a high density of microwells with limited
spacing between the microwells. The high density forces cells into the wells
and not outside on the plate" (Spec. 3: 11-13).
2. The Specification teaches "[p ]roviding wells 116 with wall
components 121 that are at an angle with respect to upper plane 114 may
cause the aspect ratio of the aggregates produced to be independent of cell
number over a wide range of aggregate sizes that fit within a well" (Spec.
15:11-13).
3. The Specification teaches
in the embodiments shown, the wall components 121 meet at a
lower apex 122. Accordingly, for a well 116 of given
dimensions, any number of cells, from 2 up to the volumetric
capacity of the well 116, will be forced to contact one another
when deposited into the well 116. In alternate embodiments
however, each well 116 may further comprise a base wall (not
shown), extending between or within the one or more wall
components.
(Spec. 15:18-23).
4. The Specification teaches
Volume 118 may be of a variety of shapes, depending on the
number of wall 25 components 121 of each sidewall, the angle
of each wall component 121 with respect to upper plane 114,
and the shape of each wall component 121. For example, in the
embodiment shown, each wall component 121 is substantially
triangular. Accordingly, each volume 118 is substantially
square pyramidal. In an alternate embodiment (not shown),
wherein each well 116 comprises a single rounded wall
component 121, the volume may be substantially conical. In
yet alternate embodiments, wherein wells 116 comprise a base
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wall, volume 118 may be, for example, substantially frusto-
pyramidal, or frusto-conical.
(Spec. 15:24--32).
5. Penick teaches "an improved method for preparing cell
aggregates for in vitro chondrogenesis studies ... that replaces the original
15-mL polypropylene [ conical] tubes with 96-well plates" (Penick 687).
6. Penick teaches the "method can now be used to efficiently
study the effects of growth factors and cytokines on the chondrogenic
potential of hMSCs ... and in other experiments that require large quantities
of individual aggregates" (Penick 687).
7. Penick teaches a method of preparing a homogenous cell
suspension and dispensing two hundred-microliter aliquots "into the wells of
an autoclave-sterilized 96-well, V Bottom, 300-µL polypropylene
microplate" (Penick 688).
8. Penick teaches "the plate is centrifuged for 5 min at 500x g and
incubated at 37°C in a humidified atmosphere of95% air and 5% CO2. In
the following 12-16 h, the cells coalesce and form a high-density cell
aggregate" (Penick 688).
9. Penick teaches"[ t ]here was no central necrosis detected in the
plate or tube aggregates. However, this can become an issue, due to mass
transport limitations, if the size of the aggregates is increased significantly
beyond what is shown here" (Penick 689).
10. Penick teaches "[b ]iochemical analyses indicate that the larger
size of the plate aggregates are a result of an increase in the number of cells
as well as higher matrix production, which suggests that the 96-well plates
are a seemingly better choice for the preparation of aggregates" (Penick
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689---690). Penick explains that the prior art use of tubes was "cumbersome,
time-consuming, and expensive for experiments requiring large numbers of
replicate cultures or study variables" and that "replacing the tubes necessary
for the production of 400 aggregates with 96-well plates results in a 90%
cost savings" (Penick 690).
11. Penick teaches:
Using our method, 400 aggregates can be prepared and
maintained in about one-fourth of the time needed when using
the tubes. This time savings is due to the time required to
uncap/recap and rack the tubes. To adapt this assay for use
with microplates, we tested a variety of 96-well polypropylene
microplates ... with different-shaped bottoms to select those
which produce consistent aggregate formation ... Microplates
that had wells with wide-angle bottoms did not allow the cell-
cell interactions that are necessary for the coalescence of the
cells, while those with narrow angles limited the
circumferential growth of the aggregates as new extracellular
matrix was fabricated by the differentiating chondrocytes. The
96-well, V Bottom, 300-µL polypropylene plates ... were
found to be the most effective for the production of our
aggregates
(Penick 690).
12. Ravkin teaches a microplate wherein each well of the
microplate includes a plurality of sub-wells thereby allowing fluid
communication between samples (Ravkin ,r 32).
13. Ravkin teaches numerous advantages of the microplate with
including: 1) "simultaneously exposing multiple biological samples ... to a
continuous fluid reagent environment", 2) "increase[ing] the number of
samples that can be tested in a given time", 3) "reduc[ing] the number of
fluid transfer operations needed to perform a given number of experiments",
and/or 4) "reduc[ing] experimental uncertainties associated with possible
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variations in fluid reagent environment across multiple samples" (see Ravkin
,r 35).
14. Ravkin teaches "[t]he sub-wells of a well ... may also have any
suitable shape(s) and/or size(s) ... Sub-wells may have any suitable
depth( s ). For example, sub-wells may be formed as deep (elongate),
intermediate-depth, and/or shallow recesses" (Ravkin ,r 42).
15. Ravkin teaches sub-wells that are frustoconical(Ravkin ,r 97).
16. Rav kin teaches a method of preparing a plurality of identical
sub-wells from a continuous fluid medium by adding sample fluid to a well
greater than the height of the inner walls of the well so that the sample fluid
has access to all sub-wells of the well and then allowing the samples to
attach themselves to the bottoms of the sub-wells (Ravkin ,r 74).
17. Rav kin teaches the "methods may be generalized to include any
procedure where reagents are added to ... identically prepared samples in
one or more steps, where the method utilizes the sub-well structure of the
apparatus to facilitate [] the preparation of identical ... samples" (Rav kin ,r
77).
18. Palecek teaches a method for growing cell aggregates in
microwells having "a depth between about 10 µm and about 1000 µm and
lateral dimensions ... between about 50 µm and about 1000 µm on a side,
and alternatively can be between about 100 µm and about 500 µm on a side"
(Palecek ,r,r 12, 14).
19. Palecek teaches "[a]dvantageously, the cells can grow in the
microwells, but not outside the microwells" (Palecek if 12).
20. Palecek teaches the microwells can be of any shape, and the
"dimensions of the microwells can be constant so that the volume, cell
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number and shape of colonies cultured in the microwells are substantially
consistent among the microwells" (Palecek ,r 13).
21. Morgan teaches a cell aggregation device with "aggregation
recesses formed to contain a region of minimum gravitational energy." The
region may be "a tapered surface terminating in a point, or a wedge-shaped
tapered surface" (Morgan 7: 10-16).
22. Oldenburg teaches a microtiter plate incorporating microwells
that "have the shape of an inverted four sided pyramid" ( 0 ldenburg 5 :61---6:
8).
23. Oldenburg teaches "[Figures] 11 and 12 showyet another
embodiment in which conical microwells 40 are utilized. In this
embodiment, the inlets of the micro wells are circles and the bottoms come to
a point" (Oldenburg 6:53-56).
Principles of Law
"[W]hen the question is whether a patent claiming the combination of
elements of prior art is obvious," the answer depends on "whether the
improvement is more than the predictable use of prior art elements according
to their established functions." KSR!nt'l Co. v. Teleflex Inc., 550 U.S. 398,
417 (2007).
Analysis
We agree with the Examiner that the combination of Penick, Ravkin,
and Palecek renders claim 82 obvious (Final Act. 5-18, FF 5-23) and we
adopt the Examiner's position as our own. We consider Appellants'
arguments below.
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Appellants contend "the cited combination of Penick, Ravkin, and
Palecek fails to teach a cell aggregate formed within at least one microwell
ofa well" (App. Br. 15). Appellants argue that "each of the wells of the 96-
well plate taught in Penick is analogous to the microwell-comprising wells
recited in the claims, and not to the 'plurality of microwells' in the base of
the wells recited in the claims" (Reply Br. 4). Appellants argue that"[ s ]ince
Penick does not teach microwell-comprising wells, it is clear that Penick
cannot teach forming cell aggregates in microwells" (id.). As to the
limitation of "within," Appellants argue that "the formation of the Palecek
cell aggregates occurs largely outside ofthemicrowell itself' (App. Br. 15).
We do not find these arguments persuasive because Appellants argue
against the references individually rather than the combination of the prior
art as a whole. "Non-obviousness cannot be established by attacking
references individually where the rejection is based upon the teachings of a
combination of references . . . . [The reference] must be read, not in
isolation, but for what it fairly teaches in combination with the prior art as a
whole." In re Merck& Co., 800 F.2d 1091, 1097 (Fed. Cir. 1986).
As discussed by the Examiner, the combination of references renders
claim 82 obvious because the ordinary artisan would have combined
Ravkin's common well device with Penick's V bottom wells for forming
multiple cell aggregates (FF 11, 12) in orderto obtain the recited cell
processing advantages ofRavkin in Penick's improved cell aggregation
method(FF 10, 13).
Indeed, Penick suggests the importance of studying cell aggregates
using plasticware that permit studying "large numbers of replicate cultures"
and a variety of "study variables" (FF 10) while obtaining time and cost
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savings based in part on reduced manipulations of the plasticware (FF 10-
11 ). Ravkin directly addresses Penick's concerns because Ravkin teaches
advantages including "simultaneously exposing multiple biological samples
... to a continuous fluid reagent environment", 2) "increas[ing] the number
of samples that can be tested in a given time", 3) "reduc [ ing] the number of
fluid transfer operations needed to perform a given number of experiments",
and/or 4) "reduc[ing] experimental uncertainties associated with possible
variations in fluid reagent environment across multiple samples." (FF 13 ).
Thus, Rav kin expressly teaches that the common well device improves the
analysis of many cultures and study variables and reduces fluid transfer
operations, addressing concerns of Penick.
As to the combination with Palecek, the reference expressly teaches
embodiments where "the cells can grow in the microwells, but not outside
the microwells" (FF 19). Because the prior art combination teaches forming
cell aggregates within each of the plurality of microwells, we are not
persuaded that the Examiner erred.
Appellants contend that "the combination of Penick, Ravkin, and
Palecek fails to teach ... a microwell with one or more sidewalls that
converges to a point to urge cells deposited in the microwell to contact each
other in the presence of a force" (App. Br. 16). First, Appellants argue that
the Examiner applies "an overly broad interpretation of the claim element
'converges to a point"' (Reply Br. 2). To support their interpretation,
Appellants cited to Figures le, Id, and Figure 2 of the Specification, as well
as the description of "any number of cells, from 2 up to the volumetric
capacity of the well 116, will be forced to contact one another when
deposited into the well 116" (Reply Br. 3; FF 3 ).
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We are not persuaded by Appellants' argument and agree with the
Examiner that "Appellants' claims do not require that this point of
convergence of the sidewalls have a specific dimension or angle and thus a v
bottom shaped microwell is deemed to meet the claim limitations" (Ans. 7).
We find that the Specification describes a variety of well shapes that
converge to urge cells to contact each other, including triangular, conical,
frusto-pyramidal, and frusto-conical wells (see FF 4). "Absent an express
definition in their specification, the fact that appellants can point to
definitions or usages that conform to their interpretation does not make the
PTO's defmition unreasonable when the PTO can point to other sources that
support its interpretation." In re Morris, 127 F.3d 1048, 1056 (Fed. Cir.
1997).
Second, Appellants argue that "the phrase 'V bottom,' or the like, is
an imprecise colloquial term that is used in the industry to describe wells in
which at least a portion of the sidewalls is generally flat and generally
converge toward the bottom of the well" (App. Br. 18). Appellants submit
evidence that, at significant enlargement, commercially available V Bottom
plates include a flat bottom portion (see App. Br. 20-22).
We are not persuaded by Appellants' argument and evidence as their
focus on commercially available V bottom plates fails to consider what the
prior art would have suggested to one of ordinary skill in the art. See In re
Young, 927 F.2d 588, 591 (Fed. Cir. 1991 ). In particular, Penick teaches
that "microplates that had wells with wide-angle bottoms did not allow the
cell-cell interactions that are necessary for the coalescence of the cells, while
those with narrow angles limited the circumferential growth of the
aggregates" (FF 11 ). In view of this teaching, we fmd the prior art fairly
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suggests narrowing the angles of the sidewalls to the micro well bottom
thereby forming a point of convergence. 11 Because the prior art suggests
microwells with sidewalls that converge to a point would have been obvious,
we are not persuaded that the Examiner erred.
Appellants argue that "one of ordinary skill in the art would not
combine the cited references" (App. Br. 24). Appellants generally argue that
Penick and Ravkin are directed to different experimental procedures and
thus may not be combined, and that "the large size of the Penick aggregates
does not lend itself to an approach of culturing in arrays of subarrays" (see
App. Br. 25-26). We address each of these arguments in tum.
Appellants first argue that Penick is directed to forming isolated
aggregates and thereby teaches away from Rav kin which is directed to
culturing multiple samples under a common condition (App. Br. 25). In
particular, Appellants argue that Ravkin's common volume of culture
medium is not consistent with Penick's teaching of forming and
differentiating chondrogenic aggregates in isolation from one another under
distinct conditions (see App. Br. 27). Appellants further argue that"[ w ]hile
Rav kin may teach wells comprising subwells of samples wherein each
subwell is addressable by a common fluid, Penick teaches away from such
an experimental setup" (App. Br. 28).
We are not persuaded by Appellants' arguments as to the teachings of
Penick. Penick teaches preparing cell aggregates from a homogenous
common cell suspension (FF 7, 8). Appellants do not cite to any disclosure
11 Moreover, both Oldenburg and Morgan, cited by the Examiner to reject
independent claim 110 and dependent claim 92, respectively, expressly teach
micro wells with sidewalls that converge to a point (FF 21-23 ).
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in Penick describing distinct conditions for forming cell aggregates. A
teaching away requires a reference to actually criticize, discredit, or
otherwise discourage the claimed solution and no specific statement in
Penick that criticizes, discredits, or discourages the use ofRavkin's common
well device was identified by Appellants. See In re Fulton, 391 F.3d 1195,
1201 (Fed. Cir. 2004). Rather than discussing differentiation, Penick is
directed to an improved method of creating cell aggregates by using wells
with narrow-angle bottoms to allow cell-cell interactions (FF 5, 10, 11).
Therefore, Penick's improvement applies not only to experiments for
differentiating chondrocytes but to "other experiments that require large
quantities of individual aggregates" (FF 6).
Appellants also argue "Penick is directed to growing cells under non-
adherent conditions and Ravkin is directed to adherent conditions." (App.
Br. 25). In particular, Appellants argue that Penick teaches the use of
polypropylene materials so that the pelleted cells adhere to one another
rather than the tube walls, and Rav kin teaches "that even if the same cell
types are seeded among the subwells, they must adhere and/ or bind to
surfaces of the subwells to form a positional cellular array" (App. Br. 31-
32). Appellants argue that "the assays disclosed in Penick and Rav kin if
combined, would render the combination inoperable" (App. Br. 33).
We are not persuaded by Appellants argument as "the test for
obviousness is not whether the features of a secondary reference may be
bodily incorporated into the structure of the primary reference ... Rather,
the test is what the combined teachings of the references would have
suggested to those of ordinary skill in the art." In re Keller, 642 F.2d413,
425 (C.C.P.A. 1981). As discussed above, the Examiner cites Ravkin for the
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advantages of a common well in combination with Penick' s micro wells
which improve cell aggregation from a common cell suspension. Whether
or not the cells adhere to the wells is not relevant to the combined teaching,
and either option would have been readily available to a person of ordinary
skill in the art. "[ A] given course of action often has simultaneous
advantages and disadvantages, and this does not necessarily obviate
motivation to combine." Medi chem, S.A. v. Rolabo S.L., 437 F.3d 1157,
1165 (Fed. Cir. 2006).
Furthermore, Appellants argue that Penick' s process for forming and
differentiating chondrogenic aggregates is incompatible with Ravkin's
testing of reagents on samples (see App. Br. 25-26, 33-34). Appellants
make several statements about how one of ordinary skill in the art would
view these two processes without citing to supporting evidence either in the
references themselves or any extrinsic source (see App. Br. 33-35). "An
assertion of what seems to follow from common experience is just attorney
argument and not the kind of factual evidence that is required to rebut a
primafaciecaseofobviousness." In re Geisler, 116F.3d 1465, 1470(Fed.
Cir. 1997). In the absence of any evidence to the contrary, we are not
persuaded that the Examiner erred in finding a reason to combine the prior
art references.
Finally, Appellants argue that the Penick's cell aggregates are too
large to be cultured in the subarrays disclosed by Ravkin or the microwells
disclosed in Palecek (App. Br. 28, 36). Appellants provide a calculation of
cellularity based on 2-3 weeks of cell growth (App. Br. 29). Without
disagreeing with Appellants' method of calculation, we fmd that the size of
the cell aggregates is a result effective variable in a known process within
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the level of one of skill in the art. See In re Boesch, 617 F.2d272, 276
(CCPA1980). For example, Penickteachesthatwithin 12-16hours, the
cells form high-density aggregates and that aggregate size should be limited
to prevent necrosis (FF 8, 9). Within these parameters, it would have been
obvious to a person of ordinary skill in the art to limit the cell aggregate
growth to the appropriately sized well.
As to both claims 82 and 110, Appellants argue "the Examiner
appears to be picking and choosing features from the prior art references to
assemble the subject-matter" (App. Br. 36). We are not persuaded by this
argument as "picking and choosing may be entirely proper in the making of
a 103, obviousness rejection, where the applicant must be afforded an
opportunity to rebut with objective evidence" In re Arkley, 455 F.2d 586,
587 (CCPA 1972).
Appellants refer to commercial success to be considered when
assessing non-obviousness without providing any supporting evidence, for
example in the form of a declaration (App. Br. 8). "Moreover, information
solely on numbers of units sold is insufficient to establish commercial
success" and no market share information was provided. In re Baxter
TravenolLabs., 952 F.2d 388,392 (Fed. Cir. 1991). Finally, Appellants
provide no showing of a nexus between the claimed method and the
commercial success of a microwell plate. In the absence of persuasive
evidence of non-obviousness, we are not persuaded that the Examiner erred
in determining that claim 82 would have been obvious over the prior art.
As to claims 85, 87-92, 94, 97, 100, and 103-111, Appellants rely on
upon their arguments regarding claim 82 (see App. Br. 37--40). Because we
18
Appeal 2018-006075
Application 12/528, 135
fmd those arguments unpersuasive, we also fmd the repetition of the same
arguments for claims 85, 87-92, 94, 97, 100, and 103-111 unpersuasive.
Conclusion of Law
A preponderance of the evidence of record support the Examiner's
conclusion that claims 82, 85, 87-92, 94, 97, 100, and 103-111 would have
been obvious.
SUMMARY
We affrrm the rejection of 111 under 3 5 U.S. C. § 112, second
paragraph.
We affrrm the rejection of claims 82, 85, 88, 94, 97, 105, and 108
under 35 U.S.C. § 103(a) as obvious over Penick, Ravkin, and Palecek.
We affrrm the rejection of claims 87 and 89-91 under35 U.S.C. §
103(a) as obvious over Penick, Ravkin, Palecek, and Deutsch.
We affrrm the rejection of claims 92, 103, 104, and 106 under 35
U.S.C. § 103(a) as obvious over Penick, Ravkin, Palecek, and Morgan.
We affrrm the rejection of claims 94 and 97 under35 U.S.C. § 103(a)
as obvious over Penick, Ravkin, Palecek, and Watanabe.
We affrrm the rejection of claim 100 under 35 U.S.C. § 103(a) as
obvious over Penick, Ravkin, Palecek, and Cruz.
We affrrm the rejection of claims 107, 109, 110, and 111 under 3 5
U.S.C. § 103(a) as obvious over Penick, Ravkin, Palecek, and Oldenburg.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).
AFFIRMED
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