Ex Parte Morita et al

Patent Trial and Appeal Board

Jul 11, 2018

11455112 (P.T.A.B. Jul. 11, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
11/455, 112 06/19/2006
23373 7590 07/13/2018
SUGHRUE MION, PLLC
2100 PENNSYLVANIA A VENUE, N.W.
SUITE 800
WASHINGTON, DC 20037
FIRST NAMED INVENTOR
IkuoMorita
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.
Q95548 9297
EXAMINER
KIM, TAEYOON
ART UNIT PAPER NUMBER
1651
NOTIFICATION DATE DELIVERY MODE
07/13/2018 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):
PPROCESSING@SUGHRUE.COM
sughrue@sughrue.com
USPTO@sughrue.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte IKUO MORITA, AKIKO KOBAYASHI, HIDESHI HATTORI,
and MASATOSHI KURODA
Appeal2017-006262
Application 11/455, 112
Technology Center 1600
Before DEMETRA J. MILLS, FRANCISCO C. PRATS, and RICHARD J.
SMITH, Administrative Patent Judges.
MILLS, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134. The Examiner has rejected
the claims for obviousness. We have jurisdiction under 35 U.S.C. § 6(b ).
We affirm-in-part.
Appeal2017-006262
Application 11/455, 112
NATURE OF THE INVENTION
The present invention relates to a cell-containing sheet that is useful as
a medical implant. Spec. 1.
According to the Specification
In recent years, a technology whereby artificial alternatives or
organized culture cells are used for implantation has been under
development and gaining attention. Representative examples of such
alternatives or cells to be implanted include artificial skin, artificial
blood vessels, and tissue composed of culture cells. In the case of
artificial skin made of synthetic polymers, for example, rejection or the
like might occur, therefore such skin is not preferable for implantation.
Meanwhile, tissue composed of cultured cells is made by culturing and
organizing cells of a patient. Thus, there is no concern about rejection
when using such tissue in the patient himself/herself. Therefore, the
tissue is preferable for implantation. Such tissue composed of cultured
cells is produced by collecting cells from a patient and culturing the
cells for the patient.
Spec. 1.
STATEMENT OF CASE
The following claim is representative.
7. A method for producing a cell-containing fine pattern
sheet comprising cells and a support comprising a
bioabsorbable material that has a cell adhesion protein-
containing layer on the surface thereof, comprising the steps of:
a) providing epithelial cells, epidermal cells, renal cells,
muscle cells, neural cells, hepatocytes, Langerhans cells,
osteocytes, chondrocytes, lymphangial cells, or periodontal
ligament-derived cells;
b) contacting said cells with the surface of a substrate for
cell arrangement having a cell adhesiveness-variation pattern
comprising cell adhesiveness promoted regions having a water
contact angle from 10° to 40°, and cell adhesiveness inhibited
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Application 11/455, 112
regions, wherein said cells adhere solely to the cell
adhesiveness promoted regions of said substrate;
c) culturing said cells adhering to the surface of said
substrate;
d) contacting said substrate adherent cells with a cell
adhesion protein-containing layer on the surface of a support
wherein said substrate adherent cells also adhere to said
support,
wherein the cell adhesion protein-containing layer has
not been subjected to a patterning treatment; and
e) removing the substrate for cell arrangement to transfer
said substrate adherent cells to said support;
wherein the support comprises an amnion in which a
layer composed of cells is removed, and the support is
supported by a biodegradable polymer,
wherein the cell-containing fine pattern sheet has a
pattern not more than 3 mm in size and is an implant.
21. The method according to claim 7, wherein the
amnion consists of stratum compactum and basal lamina.
Cited References
Yui
Shimizaki
Fishman
Morita
us 5,723,010
JP 2001-161353
US 205/0027356 Al
US 2007/0122901 Al
Mar. 3, 1998
Jun. 19,2001
Feb.3,2005
May 31, 2007
Amemiya, Human Oral Epithelial and Periodontal Ligament Cells Sheets
Cultured on Human Amniotic Membrane for Oral Reconstruction, J Oral
Tissue Engin., 89-96 (2004).
Grounds of Rejection
1. Claims 7, 9-13, 20, 30, and 31 are rejected under pre-AIA 35
U.S.C. § I03(a) as being unpatentable over Morita
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Application 11/455, 112
(W02005/038011; US2007/0122901 relied on for English
translation) in view of Yui.
2. Claims 7, 9-13, and 20-29 are rejected under 35 U.S.C. §103(a) as
being unpatentable over Morita, in view of Shimazaki ( JP 2001-
16153; English translation) in further view of Fishman.
3. Claims 7, 9-13, 20, 22-28, 32, and 33 are rejected under 35 U.S.C.
§ 103(a) as being unpatentable over Morita, in view of Amemiya
and Fishman.
FINDINGS OF FACT
The Examiner's findings of fact are set forth in the Answer, at pages
2-17. The following facts are highlighted.
1. Figures 1 and 2 of the Specification are reproduced below.
(a) (
(b)
(c)
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Appeal2017-006262
Application 11/455, 112
(b)
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L."""""""'""'""""" ........ ___________________________ l (d)
Fig. 1 shows the procedures of the present invention for allowing
cells to adhere to a substrate for cell arrangement. Spec. 7.
Fig. 2 shows the procedures of the present invention for
transferring cells to a support for cell cultivation. Id. The
explanation of the symbols used in the figures is set forth below:
1: Substrate; 2: Photocatalyst-containing cell adhesiveness-variable
layer; 3: Substrate for pattern formation; 4: Photomask; 5: Energy;
6: Cell adhesiveness-variable pattern; 7: Photocatalyst treatment
layer; 8: Cell adhesiveness-variable material layer; 11: Support;
12: Photocatalyst-containing layer; 13: Photocatalyst-containing
layer-side basal plate; 14: Photocatalyst-containing layer-side light
shielding part; 15: Substrate for cell arrangement; 16: Cell
adhesion protein-containing layer; 1 7: Cell adhesiveness promoted
region; 18: Cell adhesiveness inhibited region; 19: Cells; 20: Water
repellent material; 21: Cell adhesive material; 23: Support
comprising a bioabsorbable material. Spec. 7-8.
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Application 11/455, 112
2. Morita 1, Figure 7 is reproduced below.
a. Cause cells to adhere to a substrate comprising regions
having good cell adhesiveness and regions having inhibited
cell adhesiveness patterned there()l1,
! 17 l 1 S
15->
c. When the cells have adhered along the patt€m,
- - r, ' ~.' n ••• .:: .. :& . - - - . -· ........
e. Culture the cells on the cell culture substrate.
15-.
, 11,\._:-1:.):_
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22
g. Stimulate the cells to cause the ,~ ,,..,:;)
cells to be functional, if necessary. / I lj;_,./
!iliii141111m1a1~ 16- i
b. Inoculate cells.
d. Cause the cell array substrate to which the cells
have adhered to contact with a cell culture substrate
-15
f Remove the eel! array substrate when the cells have
successfully adhered to the eel! cultt1re substrate.
-15
1mu11B1001@ullllwnmm1 l-16
Figure 7 shows FIG. a schematic view showing an example of
the method of constructing artificial cell tissue and base material of
Morita.
Cells are inoculated on a cell array substrate (15) comprising
regions having good cell adhesiveness ( 17) and regions having
inhibited cell adhesiveness ( 18) patterned thereon. The cells are
caused to adhere to form a pattern, so that a cell adhesion substrate is
prepared. Subsequently, the cell adhesion substrate is caused to
closely contact to a cell culture substrate ( 16), so as to transfer the
1 Morita is also one of the inventors in the present application.
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Application 11/455, 112
cells. The cells are then cultured. If necessary, the cells are
stimulated with a cell stimulating factor (22). Morita ,r,r 250-251.
3. According to the present Specification
The support can be produced by allowing the cell adhesion
protein-containing layer to adhere to the surface of the
biodegradable polymer material. The cell adhesion protein-
containing layer can be formed by applying a cell adhesion
protein-containing solution to the surface of the biodegradable
polymer material. ... Cell adhesion proteins are proteins having a
function of adhering to cells. Specific examples thereof include
various types of collagens, fibronectins, laminins, vitronectins,
cadherins, gelatins, fibrinogens, fibrins, and integrins. Preferably,
the cell adhesion protein-containing layer of the present invention
is a collagen-containing layer, since it is excellent in terms of cell
adhesiveness.
Spec. 10.
4. According to the Specification the
synthetic support compris[ es] a bioabsorbable material that can be
used contains a biodegradable polymer material and a cell
adhesion protein-containing layer adhering to the surface of the
material. The biodegradable polymer material is not particularly
limited as long as it can be degraded and absorbed via in vivo
hydrolysis, enzymatic degradation, or the like and as long as it has
a certain level of mechanical strength. Preferred examples of such
material that can be used include polyglycolic acid, polylactic acid,
a copolymer of glycolic acid and lactic acid, polydioxanone, a
copolymer of glycolic acid and trimethylene carbonate, and a
mixture of polyglycolic acid and poly lactic acid. The form of such
biodegradable polymer material is not particularly limited and is
designed in accordance with the purposes thereof.
Spec. 9, italicized emphasis added.
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5. According to the Specification, the support comprising a
bioabsorbable material, may be an organism derived support.
Spec. 11.
6. According to the Specification, the organism-derived support is not
particularly limited as long as it is derived from membranous tissue
in vivo and it has a low level of antigenicity. Examples thereof
include an amnion-derived support and a chorion-derived support.
Spec. 11.
7. According to the Specification
Amnion in vivo is composed of an epithelial layer, basal lamina,
stratum compactum, a fibroblast layer, and stratum spongiosum.
Preferably, a layer composed of cells is removed from the amnion
in vivo such that a membrane comprising stratum compactum and
basal lamina is used as an amnion-derived support. Since basal
lamina is rich in collagen, it functions as a cell adhesion protein-
containing layer in an organism-derived support comprising stratum
compactum and basal lamina. Also, since stratum compactum is
rich in collagen, it can function as a cell adhesion protein-
containing layer and a membrane consisting of stratum compactum
may be used as the support of the present invention.
Spec. 12.
8. According to the Specification
Origins of these collagens which may be used are not particularly
limited. In general, such collagens that can be used are obtained
from skin, bones, cartilages, tendons, organs, or the like of
mammals including primates such as humans and monkeys,
rodents such as rabbits, mice and rats, pet animals such as canines
and felines, bovines, swines, sheep, horses, and the like. In
addition, collagen-like proteins obtained from fishes, birds, or the
like also can be used.
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Application 11/455, 112
Spec. 11.
9. Fishman discloses a microfabricated tissue as a substrate for
pigment epithelial cells transplantation for ocular implants. The
tissue may be prepared by contacting membranous tissue with a
substrate including a bioabsorbable material, which may be
submersed in phosphate buffered saline, or by coating a surface of
a membranous tissue with a bioabsorbable material, and modifying
the membranous tissue either before or after coating or contacting
the tissue with the substrate. Suitable bioabsorbable materials
include collagen; glycosaminoglycans; chitosan; poly(hydroxyl-
alkanoates ); poly(a-hydroxy acids); polyglycolic acid (PGA);
polylactic acid (PLA); etc. ,r 11; Final Act. 11.
10. Fishman defines the term membranous tissue
To mean any tissue of an animal that forms a sheet or sheath;
membranous tissue commonly encloses or delimits a tissue,
or divides an organ or tissue into separate compartments.
"Ocular membranous tissue" is used herein to mean membranous
tissue derived from the eye of an animal; lens capsule tissue and
inner limiting membrane are examples of ocular membranous
tissue, as are corneal membranes, Bruch' s membrane, and other
membranous tissues of the eye. ,r 44.
11. Shimazaki (translation) discloses a cell piece for transplantation.
This cell piece for transplantation comprises an amnion, an
epithelial stem cell tissue made to adhere onto the amnion, and an
epithelial cell proliferated from the stem cell tissue so as to cover
the amnion surface. Abstract.
12. Shimazaki (translation) discloses that the amnion is pretreated to
make it easy to remove the unnecessary upper cortex and sponge
layer which constitute an amnion. The procedure of this
pretreatment can be processed with ammonia water 10%, for
example, although there is no limitation in particular. Translation
,r 42; Ans. 7.
13. Amemiya discloses the development of human amniotic
membrane (AM), which has been cultured, and comprises mucosal
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Application 11/455, 112
epithelia and periodontal ligament (PDL) cells prepared in sheet
biomaterials from human oral epithelia and PDL cells for oral
reconstruction. Synopsis; Ans. 11.
14. Amemiya discloses that the Amnionic epithelial cells were
exfoliated and eliminated just before cell culturing. P. 91, col. 1.
15. Yui et al. teach a medical device that is implantable and tissue-
regenerative including an artificial blood vessel ( col. 1, lines 6-15),
and the device consists essentially of stratum compactum of tissue
membrane including amnion (col. 3, lines 5-8; col. 4, lines 36-44).
Yui et al. teach the use of stratum compactum as a substrate for
cell culture/growth (col. 8, lines 13-18). Yui et al. teach that a
reinforcing material can be used for the membranous material
consisting of stratum compactum of amniotic membrane, and the
material is a bioabsorbable material such as polyglycolic acid,
polylactic acid or a copolymer thereof ( col. 6, lines 43-58). Ans. 3.
16. Yui discloses that its method comprises the steps of: separating
tissue membrane including stratum compactum from tissue;
sterilizing or disinfecting the separated tissue membrane; and
removing all other layers except the stratum compactum from the
sterilized or disinfected tissue membrane using an enzyme.
Abstract.
17. Yui discloses that the human amnion comprises:
epithelium and basement membrane; stratum compactum
having a width of about 10 µm; and fibroblast. A medical
device according to the present invention consists essentially
of stratum compactum, excluding epithelium, basement
membrane and fibroblast from human amnion. Col. 4, 1. 64-col.
5, 1. 3.
PRINCIPLES OF LAW
In making our determination, we apply the preponderance of the
evidence standard. See, e.g., Ethicon, Inc. v. Quigg, 849 F.2d 1422, 1427
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Application 11/455, 112
(Fed. Cir. 1988) (explaining the general evidentiary standard for proceedings
before the Office).
"The combination of familiar elements according to known methods
is likely to be obvious when it does no more than yield predictable results."
KSR Int'! Co. v. Teleflex Inc., 550 U.S. 398,416 (2007).
Obviousness Rejection 1 - Morita and Yui
The Examiner finds that
Morita et al. teach a method of producing a cell culture substrate
comprising steps of adhering cells to the surface of a cell array
substrate having a pattern of cell-adhesiveness area and cell
adhesiveness inhibiting area, and transferring the adhered cells in a
finely patterned state onto a cell culture base material ( abstract and
par. 11, 13, 19). Morita et al. particularly disclose an embodiment
using vascular endothelial cells (par. 19) which is used for forming
artificial blood vessel as intended by Morita et al.
Ans. 2.
Morita further discloses that the regions having good cell
adhesiveness and the cell adhesiveness variation pattern have water contact
angles between 10° and 40° (par. 14). Ans. 3--4. Morita teach that the
pattern is formed with lines having widths of between 20 µm and 200 µm,
the space widths are between 300 and 1000 µm (par. 19), and thus meets the
limitation of fine pattern having no more than 3 mm in size as claimed
currently. Id. The Examiner finds that the substrate of Morita has a pattern
and the cells adhering along the pattern are considered to be a cell
arrangement. Id. The Examiner admits that Morita does not particularly
teach the support being amnion in which a layer composed of cells being
removed. Ans. 3.
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The Examiner relies on Yui to make up for this deficiency. FF 16, 17.
Yui teaches "a medical device that is implantable and tissue-regenerative
including an artificial blood vessel ( col. 1, lines 6-15), and the device
consists essentially of stratum compactum of tissue membrane including
amnion (col. 3, lines 5-8; col. 4, lines 36-44). Yui et al. teach the use of
stratum compactum as a substrate for cell culture/growth (col. 8, lines 13-
18)." Ans. 3. Yui further teaches that a reinforcing material can be used for
the membranous material consisting of stratum compactum of amniotic
membrane, and the reinforcing material is a bioabsorbable material such as
polyglycolic acid, poly lactic acid or a copolymer thereof ( col. 6, lines 43-
58). Id.
Id.
The Examiner concludes that
It would therefore have been obvious for the person of ordinary
skill in the art at the time the invention was made to use the
amnion consisting of stratum compactum of Yui et al. as a
support ... [for] the patterned cells of Morita et al.
Appellants contend that Morita does not teach that the cell culture
substrate may comprise an amnion supported by a biodegradable polymer, as
required by the claimed methods. App. Br. 9. Appellants argue that, "the
basis for this rejection rests on the assumption that one of ordinary skill in
the art will consider the 'cell culture substrate' disclosed in Morita et al. as
equivalent to the amniotic membrane disclosed by the secondary reference,
Yui et al." Id. Appellants argue that this assumption is erroneous. Id.
Appellants argue that
Morita et al. provide clear guidance to one of ordinary skill in the art
regarding the intended use for the cell culture substrate such as tissue
or organ, in disclosing that "through direct transfer of cells ... to such
biomaterial, the cells can be directly cultured in a pattern on such
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tissue or organ" ([paragraph [00275]). Therefore, taken in the context
of the application of the cell culture substrate as expounded by Morita
et al., the biomaterial taught by Morita et al. will be understood by one
of ordinary skill in the art to mean organs and tissues derived from a
patient for implantation into the patient.
App. Br. 10. Appellants further rely on the Declaration of Dr. Hattori, as
evidence, and for the proposition that
one of ordinary skill in the art as of the priority date of the present
application would have understood that the cell culture substrate for
implantation mentioned in Morita et al. is limited to biomaterials derived
from the subject to be treated, or alternatively organs for transplantation
into the subject and does not extend to biomaterials for application to the
site of treatment," such as the amnion in Yui et al. (page 2 of the
Declaration).
App. Br. 10. Appellants submit that,
Dr. Hattori concludes that one of ordinary skill in the art "would
understand that, in Morita et al., the cell adhesion substrate for
implantation is an organ or tissue that the patient needs" and therefore
one of ordinary skill in the art "would not have a reason to substitute
amnion for the cell culture substrate of Morita et al., because the patient's
body does not need amnion."
App. Br. 11.
The issues are: Does the combination of Morita and Yui teach that
the cell culture substrate or support comprises an amnion in which a layer
composed of cells is removed, and the support is supported by a
biodegradable polymer, as claimed? Has the Examiner provided a reason to
combine Morita with Yui?
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ANALYSIS
We select claim 7 as representative claim for each of the pending
rejections, as Appellants have not provided separate arguments for
individual claims in the Appeal Brief. We agree with the Examiner's fact
finding, statement of the rejection and responses to Appellants' arguments as
set forth in the Answer. We find that the Examiner has provided evidence to
support a prima facie case of obviousness. We provide the following
additional comment to the Examiner's argument set forth in the Final
Rejection and Answer.
During ex parte prosecution, claims are to be given their broadest
reasonable interpretation consistent with the description of the invention in
the specification. See, Cuozzo Speed Technolgies, LLC v. Lee, 136 S. Ct.
2131, 2144 (2016); In re Zletz, 893 F.2d 319,321 (Fed. Cir. 1989).
With respect to the claim language "amnion in which cells have been
removed," we reference the Specification, which states that
Amnion in vivo is composed of an epithelial layer, basal
lamina, stratum compactum, a fibroblast layer, and stratum
spongiosum. Preferably, a layer composed of cells is removed from
the amnion in vivo such that a membrane comprising stratum
compactum and basal lamina is used as an amnion-derived support.
Spec. 12. We find that amnion material containing stratum compactum only
is amnion in which cells have been removed.
Appellants argue that
Yui et al. does not teach the use of stratum compactum as a cell
substrate, as alleged by the Examiner. See column 8, lines 19-20 of
Yui et al. (disclosing in part that "the medical device [according to the
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claimed invention] allows the regeneration, growth and self-repair of
defective tissue."). There is no teaching or suggestion in Yui et al.
regarding the use of the stratum compactum of amnion as a substrate
for culturing cells in vitro.
App. Br. 12, bracketing original, italicized emphasis added. Appellants
argue that there is no reason to substitute the stratum compactum of Yui for
the organ cells of Morita. App. Br. 10-11.
We are not persuaded by Appellants' argument. Claim 7 is directed to
"A method for producing a cell-containing fine pattern sheet comprising
cells and a support comprising a bioabsorbable material that has a cell
adhesion protein-containing layer on the surface thereof." Claim 7 is not
specifically directed to a method of use of stratum compactum of amnion as
a substrate for culturing cells in vitro. Yui fairly discloses a medical device
or tissue prosthesis which is a sandwich-like layered structure prepared by
stitching the membrane made of stratum compactum with a fibrous material
made of bioabsorbable material. Col. 7. The bioabsorbable material may be
a poly lactic acid or copolymer. Col. 7. The tissue is formed by cell growth
using the stratum compactum as a substrate (Col. 8), in a manner similar to
that claimed.
With respect to the Appellants' argument regarding motivation to
combine Morita with Yui (App. Br. 10-11), we are not persuaded. Both of
Morita and Yui are directed to artificial cell tissue for medical tissue
replacement and methods of preparing this tissue. Morita ,r 2; Yui, col. 1.
Both of the tissue replacement materials of Morita and Yui employ a
substrate for cell growth. In Morita, the substrate may be a collagen sheet or
biomaterial derived from a living body which include tissues or organs.
Morita ,r 274. In Yui, the substrate for cell growth is amnion stratum
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compactum, connected to a polylactic acid fibrous material. Col. 8. We
agree with the Examiner that it would have been obvious to one of ordinary
skill in the art at the time of the invention to replace one well known
substrate for cell growth with another, e.g., the substrate of Yui for that of
Morita. Yui's substrate for cell growth is essentially the same as that
claimed, except for cell patterning. Put another way, Morita discloses that it
was well known in the art at the time of the invention to pattern cells on a
substrate for cell growth used for preparing artificial skin, etc. Morita ,r 2.
Thus, alternatively, it would have been obvious to one of ordinary skill in
the art to modify the substrate of Yui having the substrate for cell growth is
amnion stratum compactum, connected to a polylactic acid fibrous material,
to include patterning as disclosed by Morita. This is because Morita
discloses that, "[ c ]ulture of cells on such substrate enables adhesion of a
greater number of cells to a surface on which collagen or the
like has been patterned." Morita ,r 6. In addition, an advantage of substrate
cell patterning is that
Through the formation of such cell adhesiveness variation
pattern, vascular endothelial cells caused to adhere and then
transferred in a linear pattern efficiently form a tissue; that
is, a linear capillary vessel. When a cell pattern where a
plurality of lines are arranged without crossing each other is
formed, the space widths between the lines on which cells
are adhered are each set to be equal to or above a specific
value as described above. Accordingly, the cells can be
prevented from extending pseudopodia between the lines at
the time of their tissue formation, which would distort the
lines.
Morita ,r 41.
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The Examiner, additionally, concludes that based on the given broad
definition of the term "biomaterial" for use as a substrate for cell growth in
Morita (which may be a biomaterial (tissue or organ) derived from a living
body), one skilled in the art would understand that the scope of the
biomaterial for use as a substrate for cell growth in Morita includes any
known material derived from living bodies, and includes amnion or amniotic
membrane which is derived from a placenta (an organ). Ans. 13.
The Examiner further concludes that Yui discloses that the amnion-
derived substrates are used for cell carriers, and for implantation, and one
skilled in the art would recognize that the amnion-derived substrates taught
by Yui et al., as a suitable biomaterial for the method of Morita et al. Id.
We agree with the Examiner that the evidence of record supports the
Examiner's finding that the combination of Morita and Yui teach that the
cell culture substrate or support comprises an amnion in which a layer
composed of cells is removed, and the support is supported by a
biodegradable polymer, as claimed.
We carefully considered the Declaration of Dr. Hattori, and have
considered his conclusion that from his reading of Morita, that the cell
adhesion substrate for implantation described therein is an organ or tissue
that the patient needs, for instance for the purpose of replacement.
Declaration p. 2-3.
In spite of the technical conclusion of Dr. Hattori in his Declaration
that the biomaterial substrate of Morita is limited to organs or tissues, the
Board has broad discretion as to the weight to give to declarations offered in
the course of prosecution. See Velander v. Garner, 348 F.3d 1359, 1371
(Fed. Cir. 2003) ("[A]ccord[ing] little weight to broad conclusory statements
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[in expert testimony before the Board] that it determined were unsupported
by corroborating references [was] within the discretion of the trier of fact to
give each item of evidence such weight as it feels appropriate.").
Furthermore, Dr. Hattori' s conclusion has no specific relevance as to the
legal conclusion whether it would have been obvious to one of ordinary skill
in the art to substitute one well known cell growth substrate for another, in a
tissue prosthesis.
Unexpected Results
Appellants argue that the method of the invention produces a cell-
containing fine pattern sheet that
possesses unexpected and superior properties that distinguish it as
being unobvious in the context of the cited references. Appellant had
previously highlighted that the mechanical strength of amnion allows
it to be fixed on the site to be treated by suturing. See Response filed
March 24, 2016 (describing that "[w]hen the cell containing sheet of
the present invention is sutured at the site, the cell pattern on the sheet
is fixed to the site keeping the contact between the site and the aligned
cells in a predesigned manner for a sufficient period of time,"
facilitating rapid recovery).
App. Br. 15.
The Examiner responds, arguing Appellants have not provided an
evidentiary showing of synergistic effect provided by the claimed method
and device layering, or unexpected results. Ans. 16. In particular, the
Examiner argues that,
Even if the alleged synergistic effect is considered, there is no clear
evidence supporting the unexpected synergism. The alleged
synergism is based on the use of the cell containing sheet of the
instant invention (i.e. amnion) by suturing it onto the tissue site.
Appellant alleged that Example 4 of the instant specification
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Id.
demonstrates such alleged effect. However, it is the Examiner's
position that the alleged "synergism" has not been established.
Example 4 does not show any evidence other than the use of the
periodontal ligament-derived cell containing sheet made of an
amnion-derived support, and the results obtained from the
implantation of the sheet secured by suturing on to the parietal bone.
The data shown in Example 4 compare the control group (with the
amnion sheet only) and the experimental group (with the cell-
containing sheet on which the pattern of human periodontal ligament
cells). It is the Examiner's understanding that the results of "rapid
recovery" are shown in the experimental group which contains
periodontal ligament cell in pattern compared to the control group
having no cells on the amnion-derived sheet. There is no "synergism"
shown in Example 4 based on the use of amnion and suturing as
alleged.
For the reasons cited by the Examiner, we are not persuaded by
Appellants' arguments or evidence of unexpected results.
We find no error in the Examiner's prima facie case of obviousness.
We do not find Appellants have provided evidence to rebut the Examiner's
prima facie case of obviousness. The preponderance of the evidence
supports the Examiner's obviousness rejection.
Obviousness Rejection 2 -Morita, Shimizaki, and Fishman
Morita is relied on by the Examiner for its disclosure discussed above.
The Examiner further relies on Shimazaki as teaching
an amniotic membrane (AM) carrier for cell transplantation,
and the AM carrier is obtained from amniotic membrane with a
sponge layer (stratum spongy) and an upper cortex ( epithelial
layer) being removed, resulting in a dense layer (stratum
compactum) and a basement membrane (basal lamina) left (see
par. 44 of the English translation).
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Ans. 7. The Examiner concludes that it would have been obvious to replace
the amnionic carrier for cell transplantation of Shimazaki for the cell culture
substrate of the method of Morita because both of the tissue replacement
materials of Morita and Shimazaki employ a substrate for cell growth. In
Morita, the substrate may be a collagen sheet or biomaterial derived from a
living body which include tissues or organs. Morita ,r 274. In Shimazaki,
the substrate for cell growth ( cultivation ,r 55) is amnion stratum compactum
( cells removed), which is used to prepare cell pieces for transplant.
Shimazaki translation ,r,r 1, 14, 23, 42. We agree with the Examiner that it
would have been obvious to one of ordinary skill in the art at the time of the
invention to replace one well known substrate for cell growth with another,
e.g., the substrate of Shimazaki for that of Morita.
Fishman discloses that a microfabricated membranous tissue layer
such as amniotic membrane on a carrier matrix aids in its implantation into
the body. Fishman ,II 1, 68-69, 79. The carrier matrix of Fishman may be a
biodegradable, bioabsorbable polymeric material such as polylactic acid
(par. 11, 68-69, 79). Ans. 8.
It would therefore have been obvious to a person skilled in the
art to modify the AM carrier of Shimazaki et al. to have a
biodegradable carrier matrix as a support. Since the use of the
biodegradable carrier matrix for the support of a membranous
tissue is known in the art as taught by Fishman et al., and the
AM carrier of Shimazaki et al. is considered the same
membranous tissue of Fishman et al., one skilled in the art
would combine prior art elements according to the known
method to yield predictable results.
Final Act. 8.
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Regarding this rejection, Appellants rely on their previous arguments
with respect to Morita, the Declaration of Hattori, and unexpected results.
App. Br. 18-20. We are not persuaded by these arguments for the reasons
presented herein, and the rejection Claims 7, 9-13 and 20, 22-29 is
affirmed.
Claim 21
While not specifically indicating argument of claim 21, Appellants do
argue that, "a combination of the cited references will not lead one of
ordinary skill in the art to the claimed invention, since the claimed method
comprises the use of amnion that consists of stratum compactum and basal
lamina (See Figure on page 17, Amendment filed February 7, 2012)," which
is the subject matter of claim 21. App. Br. 20.
We are not persuaded that the Examiner has provided evidence to
support a prima facie case of obviousness of claim 21. According to
Appellants' Specification, the amnion is composed of an epithelial layer,
basal lamina, stratum compactum, a fibroblast layer, and stratum
spongiosum. Shimizaki translation indicates that the amnion is treated to
remove the epithelial layer, sponge layer and upper cortex. i-fi-f l 4, 64. The
Examiner does not indicate and Shimazaki does not appear to disclose that
the fibroblast layer has been removed from the amnion. The rejection of
claim 21 is reversed.
Obviousness Rejection 3 -Morita, Amemiya and Fishman
The disclosures and arguments with respect to Morita and Fishman
are discussed above, herein. Amemiya is relied on by the Examiner for the
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disclosure of amniotic membrane (AM) carrier being used for sheets
comprising human oral epithelial cells or periodontal ligament cells for oral
reconstruction. . . . Amemiya et al. teach that amniotic epithelial cells were
exfoliated and eliminated (seep. 91, left col. "Human AM preparation").
Regarding this rejection, Appellants rely on their previous arguments
with respect to Morita, the Declaration of Hattori, and unexpected results.
App. Br. 18-20.
Appellants further argue that the amniotic membrane allegedly taught
by Amemiya "is not equivalent to the amnion of the claimed method. The
claimed method encompasses an amnion in which a layer composed of cells
is removed, which comprises stratum compactum and basal lamina as
defined by the specification (page 12, lines 6-9)." App. Br. 23.
We are not persuaded. Amemiya et al. teach that amniotic epithelial
cells were exfoliated and eliminated (seep. 91, left col. "Human AM
preparation"). Thus, Amemiya discloses removal of a layer of amnionic
cells.
The obviousness rejection is affirmed.
CONCLUSION OF LAW
The cited references support the Examiner's obviousness rejections,
which are affirmed for the reasons of record. The rejection of claim 21 over
Morita in view of Shimizaki and Fishman is reversed. Arguments not made
are waived.
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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-IN-PART
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