OSAKA UNIVERSITY et al.

Patent Trials and Appeals Board

Sep 1, 2020

2020001014 (P.T.A.B. Sep. 1, 2020)

UNITED STATES PATENT AND TRADEMARK OFFICE
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O. Box 1450
Alexandria, Virginia 22313-1450
www.uspto.gov
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
14/767,601 11/10/2015 Ken NAKATA 3190-198 1659
33432 7590 09/01/2020
KILYK & BOWERSOX, P.L.L.C.
400 HOLIDAY COURT
SUITE 102
WARRENTON, VA 20186
EXAMINER
LIU, SAMUEL W
ART UNIT PAPER NUMBER
1656
NOTIFICATION DATE DELIVERY MODE
09/01/2020 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):
LKILYK@KBPATENTLAW.COM
docketing@kbpatentlaw.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte KEN NAKATA, YUKIHIRO SATO, DAISUKE IKEDA, and
ICHIRO FUJIMOTO
__________

Appeal 2020-001014
Application1 14/767,601
Technology Center 1600
__________

Before ANTON W. FETTING, ULRIKE W. JENKS, and
RACHEL H. TOWNSEND, Administrative Patent Judges.

TOWNSEND, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims to a
collagen sponge, which have been rejected as obvious. We have jurisdiction
under 35 U.S.C. § 6(b).
We affirm.

1 We use the word “Appellant” to refer to “applicant” as defined in 37
C.F.R. § 1.42. Appellant identifies the real parties in interest as Osaka
University and Koken Co., LTD. (Appeal Br. 3.)
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STATEMENT OF THE CASE
According to Appellant’s Specification, complex cartilage injury does
not heal naturally “owing to a small number of blood streams.” (Spec. ¶ 2)
Regenerative medicine involving cartilage implant has been investigated to
repair such injuries. (Id. ¶ 3.) Appellant’s Specification explains that
a substrate to be implanted into a tissue to be subjected to a
mechanical load is required to have a structure easily bonded to
the implantation site and to have physical properties equivalent
to those of a tissue into which the substrate is to be implanted
so that a patient subjected to implantation can resume a daily
life immediately.
(Id. ¶ 5.) Appellant’s invention is directed to a collagen sponge having such
strength and a pore structure for allowing cells to infiltrate into it. (Id. ¶ 7.)
Claims 1, 5, and 8–10 are on appeal. Claim 1 is illustrative and reads
as follows:
1. A collagen sponge consisting essentially of collagen,
wherein the collagen sponge has a compressive stress of
from 10 kPa to 30 kPa when loaded with 10% strain, has in its
surface and inside a pore structure having a mean pore diameter
ranging from 50 μm to 400 μm, and has a pore diameter
standard deviation equal to or less than 40% of the mean pore
diameter.
(Appeal Br. 17.)

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The prior art relied upon by the Examiner is:
Name Reference Date
Silver et al. US 4,970,298 Nov. 13, 1990
Ken et al. JP 2008-079548 Oct. 4, 2008
The following ground of rejection by the Examiner is before us on
review:
Claims 1, 5, and 8–10 under 35 U.S.C. § 103(a) as unpatentable over
Ken2 and Silver.
DISCUSSION
The Examiner finds that Ken teaches a collagen “carrier composition”
that “has stress (compressive strength) of 10–30 kPa at 10% load after
freeze-drying the collagen dispersion liquid solution or mixture and an
insolubilization process.” (Non-Final Action 3.) The Examiner further finds
that Ken teaches the collagen composition after processing is porous. (Id.;
Ans. 5.) Furthermore, the Examiner finds that Ken teaches the desired pore
size is achieved by choosing the proper freeze-drying process. (Non-Final
Action 3, 5–6.)
The Examiner finds that the claimed mean pore diameter range and
pore diameter standard deviation of equal or less than 40% of the mean pore
diameter would have been obvious in light of the teachings of Silver. (Non-
Final Action 4; Ans. 5.3) In particular, the Examiner finds that Silver
teaches the pore size of a collagen sponge made by freeze drying a collagen
dispersion can be controlled by changing the extent of collagen fiber

2 The Examiner relied upon the computer generated English translation
provided by Appellant (Non-Final Action dated Jan. 8, 2019 at 3), as do we.
3 We refer to the Examiner’s Answer dated September 27, 2019.
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dispersion, the pH of the dispersion, and the freezing temperature. (Id.) The
Examiner further finds that Silver teaches a uniform collagen sponge whose
optimum structure has a uniform pore size where the “preferred pore size
[is] about 100 μm.” (Non-Final Action 4 (emphasis omitted); Ans. 5.) The
Examiner also finds that Silver teaches the uniform pore size is suitable for
wound healing. (Non-Final Action 4; Ans. 5–6.)
The Examiner concludes that it would have been obvious in the
process of Ken to control the parameters taught by Silver to arrive at a
sponge with the pore size and uniformity claimed and also having the
compressive strength properties taught by Ken, which is taught to result
from “lyophilizing (a freeze-drying process) a high concentration of collagen
dispersion solution (see p. 1, lines 5–7, ‘584).” (Non-Final Action 4; Ans.
6–7.)
We agree with the Examiner that the combination of Ken and Silver’s
teachings make prima facie obvious the claimed collagen composition. In
particular, Ken teaches that after freeze drying a collagen dispersion to
achieve the desired pore size (Ken ¶ 14), an insolubilization process is
performed that results in an increase in the physical strength of the freeze-
dried collagen material (Id. ¶ 15 (“By performing an insolubilization
process, physical strength can be raised.”).) Several different
insolubilization methods are mentioned for use by Ken. (Id. ¶¶ 16–17.)
Ken teaches the importance of having a cartilaginous material “which
has stress of 10-30 kPa at the time of 10% load” is so that the material will
have a particular physical strength when inside the body and receiving a load
similar to the load a living body’s cartilaginous tissue receives. (Id. ¶¶ 7, 11,
18.) The porous structure is important to Ken so that the cartilaginous
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material can “have pore for a cell to enter,” such as chondrocytes, and so
that cell culturing can be attained and thus “obtain a transplantation thing
more similar to a body tissue by culture.” (Id. at Abstract, and ¶¶ 3, 6, 8,
11.) Ken teaches that a dispersion liquid solution of 50 mg/ml or 70 mg/ml
is more desirable to use than 30 mg/ml to obtain a collagen “carrier of
physical properties similar to a cartilaginous tissue.” (Id. ¶ 11.) Ken also
teaches that the pH of the cartilaginous dispersion prior to subjecting the
dispersion to freeze drying and insolubilization is between pH 4–10. (Id. ¶
10.)
Silver teaches pore size of collagen material can be controlled by
“changing the extent of fiber dispersion, the pH of the collagen dispersion,
and the freezing temperature.” (Silver 8:15–20.) Furthermore, Silver
teaches that “[c]ell growth on collagen in cell culture is dependent on the
three dimensional structure.” (Silver 7:54–56.) Silver teaches “[f]ibrillar
structure appears to be an important parameter in the design of a biomaterial
as well as porous structure allowing tissue ingrowth into the material.” (Id.
at 8:2–5.) Silver goes on to state that “[a] fibrous structure associated with
an average pore size of 50 to 250 μm and, preferably 100μm ± 50,
containing channels is an ideal structure for a collagen-based material for
tissue ingrowth” (id. at 9:61–65), and further that “[a] collagen sponge of the
optimum structure, to aid in the healing of a wound, has pores throughout
the sponge which are relatively uniform size” (id. at 11:7–9). Silver further
teaches that
To obtain a sponge of the optimum structure, the pH of the
dispersion is between about 3.0 and about 5.0 and more
preferably between about 3.0 and about 3.5 and the freezing
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temperature is between about -30° C. and about -50° C. and
more preferably between about -30° C. and -40° C.
(Id. at 11:14–19; see also Table I, and Example 20.)
“In determining whether obviousness is established by combining the
teachings of the prior art, the test is what the combined teachings of the
references would have suggested to those of ordinary skill in the art.” In re
GPAC Inc., 57 F.3d 1573, 1581 (Fed. Cir. 1995) (internal quotations marks
and citations omitted). We find that, given the teachings of Ken and Silver
discussed above, one of ordinary skill in the art would have been motivated
by Silver to control the freeze-drying process of Ken to provide for a
collagen sponge that has relatively uniform size pores of optimally 100 μm ±
50 and then subsequently proceed with the insolubilization step of Ken to
arrive at a collagen structure that is both porous with uniform pore size and
has an increase in the physical strength of the freeze-dried collagen material
such that it has compressive strength of 10–30 kPa at the time of 10% load.
Such a collagen sponge would be a structure within the scope of Appellant’s
claim 1.
For the reasons just discussed, we disagree with Appellant that the
Examiner impermissibly picks and chooses isolated statements to arrive at
the claimed invention because “there is no teaching from either cited
reference that would tie everything together to arrive at a collagen sponge
having both the claimed compressive stress and the claimed mean pore
diameter and pore standard deviation” (Appeal Br. 14–15).
We also do not find persuasive Appellant’s argument that Ken’s
teaching of a stress of 10–30 kPa at the time of 10% load in paragraph 7 “is
not a clear and unambiguous showing of the claimed compressive stress”
(Reply Br. 5). In particular, Ken refers to testing the physical strength of the
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collagen carrier produced with a compression load where the results were 33
kPA at 20% load, 22.5 kPA at 10% load and 15 kPa at 5% load. (Ken ¶ 20.)
Further, we note that although Appellant provides the Declaration of
inventor Ichiro Fujimoto, Ph.D.4 to address non-obviousness of the claimed
invention from Ken and Silver, Dr. Fujimoto does not contradict the
Examiner’s assertion that the collagen substance taught thereby has the
claimed compressive strength. Instead, Dr. Fujimoto focuses solely on pore
diameter of working example 1 of Ken and it not being within the claimed
standard deviation range.
Consequently, we conclude that the stress of 10–30kPA at 10% load
discussed at paragraph 7 of Ken is a compression stress as is claimed.
Appellant’s argument that Silver at column 9, lines 59–63 does not
state that the pore sizes are uniform (Appeal Br. 10) is not persuasive of
Examiner error. As noted above, elsewhere, Silver explicitly states that the
“optimum structure” of the collagen sponge to aid in wound healing “has
pores throughout the sponge which are of relatively uniform size” and
preferably have a diameter of 100 μm ± 50. (Silver 11:7–14.)
Appellant’s argument that the Examiner “does not explain how the
collagen sponge of [Ken] can somehow be manipulated to maintain the
compressive strength set forth in [Ken] and yet achieve the pore diameter
standard deviation that allegedly Silver et al. provides” (Appeal Br. 10) is
unavailing. The Examiner indicates that, as taught by Silver, modifying the
dispersion parameters of pH and temperature and the extent of dispersion

4 Declaration of Ichiro Fujimoto, Ph.D. dated Nov. 22, 2018, hereinafter
Fujimoto Declaration.
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that is subsequently to be freeze-dried would control the pore size. (Ans. 9.)
As we noted above, Ken teaches preparing a dispersion liquid of collagen
before freeze drying and that the compressive strength is raised by the
insolubilization process. (Ken ¶ 15; see also id. ¶7.) Thus, we conclude that
the Examiner explains the parameters of Ken—pH, temperature, and extent
of dispersion—that are modified in order to achieve a collagen carrier with
the claimed compressive strength and pore diameter size and diameter
standard deviation claimed.
Appellant argues that Dr. Fujimoto’s declaration cannot be “ignored
or discounted” in maintaining the obviousness rejection. (Appeal Br. 9–10.)
We agree. However, we do not find Dr. Fujimoto’s declaration to establish
non-obviousness. The fact that working example 1 of Ken, reproduced by
Dr. Fujimoto (Appeal Br. 10; Fujimoto Declaration ¶ 6), does not achieve
the claimed pore diameter standard deviation does not establish non-
obviousness because the Examiner relied upon substituting the preferred pH
and temperature conditions taught in Silver to obtain uniform pore size
having the claimed standard deviation, e.g., pH 3–5 and -30 ºC – -50 ºC
(Silver 11:7–19). Working example 1 of Ken employed a pH of 9 and
freezing took place at -20 ºC. (Ken ¶¶ 19–20.) As Silver explains, “the
effect of pH is significant between -35 ºC. and -20 ºC.” (Silver 10:61–11:6.)
Indeed, Table 1 of Silver demonstrates the effects at -30 ºC. (Id. at cols. 14–
15.) At pH of 2.1, pore size was 44 ± 8 μm, whereas at pH 3, pore size was
68 ± 14 μm and at pH 3.5 pore size was 110 ± 15 μm.
Furthermore, we agree with the Examiner that working example 4 of
Silver is not the “only example relating to a collagen sponge” in Silver (Ans.
13; Appeal Br. 12), and is not, in fact, the closest prior art teaching of Silver.
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Indeed Example 20 is described as “Preparation of Collagen Sponges of
controlled Pore Size and Morphology,” whereas Example 4 is simply
described as “Preparation of Collagen-based Sponges and Sheets.” We note
that the freezing in Example 4 is carried out at -100 ºC (Silver 19:11–15),
which is at least 50 ºC cooler than what Silver explains is important to
obtain uniform pore size. And, Silver explains that using freezing
temperatures of -80 ºC compared to temperatures of -20 ºC results in smaller
pore sizes. (See, e.g., id. at 8:35–39.) Table 1 of Silver shows the change in
pore size with changes in pH and temperature, demonstrating that 110 ±15
μm pore size is achieved at pH 3.5 and -30 ºC, but pore size of 14 ±2 μm
pore size is achieved at pH 3.5 and -80 ºC. Consequently, we disagree with
Appellant and Dr. Fujimoto that Example 4 of Silver is a “relevant” example
of Silver, when it comes to demonstrating that Silver does not teach a
sponge having a claimed pore size within the claimed range and within the
claimed percent standard deviation of mean pore diameter. That is also true
with respect to the slight variations of Silver’s Example 4 prepared by Dr.
Fujimoto, as each of those variations also involved freezing the collagen
solution at -100 ºC prior to freeze-drying. (See Fujimoto Declaration
Exhibit 1 ¶¶ 3–4.)
Thus, Dr. Fujimoto’s Declaration evidence was not improperly
ignored by the Examiner. Rather, we conclude that the evidence provided as
to Example 4 of Silver and the lack of pore diameter meeting the claimed
limitation is not evidence of a comparison to the closest prior art teaching
from Silver regarding uniform pore size. We do note, however, as the
Examiner pointed out that the standard deviation for pore diameter of
Example 4 on average does fall within the 40% or less standard deviation
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claimed. (See Fujimoto Declaration Exhibit 1, Table 1, and ¶ 7 (“Even
Sponge I had a standard deviation of 40%.”).) Thus, the Declaration
supports the Examiner’s position that uniformity of pore size of about 100
μm ± 50 with a standard deviation of 40% or less following the process of
Silver with the optimum pH and temperature conditions would be expected
to be achieved.
In addition, that Example 4 of Silver did not have the claimed
compressive strength (Appeal Br. 10) is not telling of non-obviousness
because the Examiner relies on Ken’s teaching that the insolubilization step
after freeze-drying will increase the compressive stress. Appellant does not
provide any evidence to establish that one of ordinary skill in the art would
not have reasonably expected the compressive strength of any sponge
produced by the freeze-drying process of Silver (much less using the
optimum conditions to achieve an average pore size of about 100 μm ± 50
and of relatively uniform pore size) to have been increased to within the
claimed range by adding afterward the insolubilization process described in
Ken. The Declaration evidence does not address the contribution of an
insolubilization process as described in Ken at all to compressive strength.
Instead, Dr. Fujimoto simply asserts that altering the pore diameter standard
deviation will have an effect on compressive strength; they are not isolatable
properties. (Fujimoto Declaration ¶ 8.) While Dr. Fujimoto’s statement
may be true, it does not speak to the effect of an additional insolubilization
process on the collagen after having been freeze-dried on compressive
strength.
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Thus, we do not find Appellant’s evidence persuasive to establish the
sponge recited in claim 1 is not obvious from the combination of teachings
of Ken and Silver.
Regarding claim 8, which is a product-by-process claim, we agree
with the Examiner (Ans. 4) that it is the product that must be established to
be non-obvious. “The patentability of a product does not depend on its
method of production. If the product in a product-by-process claim is the
same as or obvious from a product of the prior art, the claim is unpatentable
even though the prior product was made by a different process.” In re
Thorpe, 777 F.2d 695, 697 (Fed. Cir. 1985) (citations omitted). For the
reasons discussed above, Appellant has not persuaded us with appropriate
evidence that the claimed product is not obvious from Ken and Silver. That
Silver may not use any centrifugation prior to freeze-drying (Appeal Br. 13;
Fujimoto Declaration ¶ 9), is thus not compelling of non-obviousness of the
claimed collagen composition.
Claims 5, 9, and 10 have not been argued separately and therefore fall
with claims 1 and 8. 37 C.F.R. § 41.37(c)(1)(iv).
DECISION SUMMARY
In summary:
Claims
Rejected
35 U.S.C.
§
Reference(s)/Basis Affirmed Reversed
1, 5, 8–10 103 Ken, Silver 1,5, 8–10

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TIME PERIOD FOR RESPONSE
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a). See 37 C.F.R.
§ 1.136(a)(1)(iv).
AFFIRMED