Weon Ik Choi et al.

Patent Trials and Appeals Board

Oct 27, 2020

13386111 - (D) (P.T.A.B. Oct. 27, 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.
13/386,111 01/20/2012 Weon Ik Choi HI-1 US (044284.0002) 9732
27104 7590 10/27/2020
FENNEMORE CRAIG, P.C.
1700 Lincoln Street Suite 2400
DENVER, CO 80203
EXAMINER
MCNEIL, STEPHANIE A N
ART UNIT PAPER NUMBER
1653
MAIL DATE DELIVERY MODE
10/27/2020 PAPER
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.
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte WEON IK CHOI, WOOK CHUN, and
JAE DEUK JUNG
____________

Appeal 2019-006870
Application 13/386,111
Technology Center 1600
____________

Before FRANCISCO C. PRATS, ULRIKE W. JENKS, and
MICHAEL A. VALEK, Administrative Patent Judges.

VALEK, Administrative Patent Judge.

DECISION ON APPEAL
Appellant1 submits this appeal2 under 35 U.S.C. § 134(a) involving
claims to a method of processing an allograft of viable skin for
transplantation. We have jurisdiction under 35 U.S.C. § 6(b).
We REVERSE.

1 We use the word “Appellant” to refer to “applicant” as defined in
37 C.F.R. § 1.42. Appellant identifies CG BIO CO., LTD. as the real party
in interest. Appeal Br. 2. Herein, we refer to the Final Action mailed
October 11, 2018 (“Final Act.”); Appellant’s Appeal Brief filed June 5, 2019
(“Appeal Br.”); Examiner’s Answer mailed July 31, 2019 (“Ans.”); and
Appellant’s Reply Brief filed September 23, 2019 (“Reply Br.”).
2 This Appeal is related to Appeal 2019-006119 (Application 13/392,596),
decision entered August 10, 2020.
Appeal 2019-006870
Application 13/386,111
2
STATEMENT OF THE CASE
The Specification states
[t]he present invention relates to a method of processing
allograft skin for transplantation and a cryopreserved allograft
skin produced thereby. More specifically, the present invention
relates to a method in which a cryoprotectant is prepared by
adding sucrose to basic constituents comprising dimethyl
sulfoxide, an animal cell culture medium and fetal bovine
serum, and then the resulting solution is used to subject skin
tissue for transplantation to a freezing process.
Spec. ¶ 1. The Specification explains that using “the optimal mixing ratio of
sucrose, fetal bovine serum and dimethyl sulfoxide [in the cryoprotectant
solution] improves cell viability.” Id. ¶ 11. According to the Specification,
sucrose is preferably dissolved in the basic constituents-mixed
solution as 25 to 40 wt% in the final concentration. If the
concentration of sucrose is less than 25 wt%, the effects of
sucrose to protect and stabilize cell membranes and cell
membrane proteins needed to improve cell viability may be
insufficient. If the concentration of sucrose is greater than 40
wt%, cell death rate may be increased due to high concentration
of sugar ingredients.
Id.
Claims 1, 3, and 5–7 are on appeal and can be found in the Claims
Appendix of the Appeal Brief. See Appeal Br. 21–22. Claim 1 is
representative and reads as follows:
1. A method of processing allograft of viable skin for
transplantation comprising:
i) mixing a cryoprotectant solution to include dimethyl
sulfoxide, sucrose, an animal cell culture medium and fetal
bovine serum to obtain a cryoprotectant solution in which the
mixing ratio of dimethyl sulfoxide, the animal cell culture
medium and fetal bovine serum is 1 : 3-5 : 4-6 based on weight,
and the sucrose has a final concentration of 25% to 40% by
weight of the cryoprotectant solution;
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ii) penetrating the cryoprotectant solution into a separated
allograft of viable living skin for 6 to 24 hours; and
iii) freezing the cryoprotectant-penetrated skin in a
controlled rate freezer at a freezing rate of from -0 .1 to -7°C per
minute.
Id. at 21.
Appellant seeks review of the following rejections:
I. Claims 1, 3, and 5 under 35 U.S.C. § 103 as unpatentable over
Gabbai,3 in view of Livesey,4 Applegate,5 Taylor,6 and Brockbank;7
and
II. Claims 6, and 7 under 35 U.S.C. § 103 as unpatentable over Gabbai,
in view of Livesey, Applegate, Taylor, Brockbank, and Wang.8
See Appeal Br. 3–19.
Analysis
Both of Examiner’s obviousness rejections are premised on the same
combination of Gabbai, Livesey, Applegate, Taylor, and Brockbank as
applied to independent claim 1. Final Act. 6 (rejecting claims 6 and 7 as
obvious over these references as applied to claim 1). Accordingly, we
consider the obviousness rejections together, focusing on claim 1 as
representative of the claims on appeal. The issue is whether a

3 US 2009/0029340 A1, published Jan. 29, 2009 (“Gabbai”).
4 US 2006/0210960 A1, published Sept. 21, 2006 (“Livesey”).
5 L.A. Applegate et al., Whole-Cell Bioprocessing of Human Fetal Cells for
Tissue Engineering of Skin, 22 Skin Pharmacol Physiol 63–73.
(2009)(“Applegate”).
6 US 6,492,103 B1, issued Dec. 10, 2002 (“Taylor”).
7 US 2004/0067480 A1, published April 8, 2004 (“Brockbank”).
8 X. Wang et al., The Cryopreservation of a Tissue Engineered Dermal
Replacement by Programmed Freezing, Proceeding of the 2005 IEEE, Eng’g
in Medicine and Biology 27th Annual Conf. (2005)(“Wang”).
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preponderance of the evidence supports Examiner’s conclusion that cited
prior art renders the method of claim 1 obvious.
Examiner finds Gabbai teaches a method for cryopreserving skin
involving the use of a cryoprotective composition that includes
“dimethylsufoxide (DMSO), sucrose, and culture medium” as
“cryoprotective agents” and fetal calf serum as a stabilizer. Final Act. 2–3.
Examiner acknowledges “Gabbai is silent as to the ratio [of] DMSO, fetal
bovine serum, and culture medium, and the percent sucrose.” Id. at 3.
Examiner determines Livesey teaches cryoprotectant solutions “contain[ing]
between 6% and 12% sucrose” that also “comprise a mixture of other
sugars/nonpenetrating cryoprotectants, and that the total amount of these
compounds is up to 46% of the solutions.” Id. (referring to amounts of
“dextran, raffinose, PVP, trehalose, and sucrose” in “formulations VS2 –
VS4” in Livesey ¶¶ 88–90, 145). Examiner further determines that Taylor
and Brockbank teach cryoprotectant solutions containing sucrose in ranges
(i.e., “1% to 30%” and “in a concentration of 0.1 to 2 M”) that partially
overlap with the “25% to 40% by weight” range in claim 1. Id. at 4–5.
Moreover, Examiner finds Applegate discloses a cryoprotectant solution
containing DMSO, animal cell culture medium, and fetal bovine serum at a
ratio within the “1 : 3–5 :4–6” range recited in claim 1. Id. at 4.
Based on these teachings, Examiner concludes it would have been
obvious to “use the amounts of cryopreservation solution components taught
by Applegate and Taylor because . . . Gabbai teaches each of the
components is useful . . . and Applegate and Taylor provide examples of
amounts that are useful for cryopreservation of tissues.” Id. at 6. Examiner
further concludes that it would have been obvious to combine Livesey’s
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teaching regarding freezing rate and Brockbank’s teaching regarding
incubation time to arrive at the claimed method. Id.
Appellant disputes Examiner’s obviousness rejections in several
respects. In particular, Appellant contends the rejection relies on “improper
hindsight” to arrive at the components and concentrations of the
cryoprotectant solution recited in step i) of claim 1. See Appeal Br. 11–14.
Accordingly to Appellant, Gabbai “merely provides a list of
cryoprotectants––good and bad––that are in common use” and does not
recommend the selection of any particular component, much less the
particular combination of ingredients, recited in claim 1. Id. at 13–14.
Moreover, Appellant urges that the ranges Examiner points to in Taylor and
Brockbank9 relate to “less preferred” solutions for preserving different types
of tissue. Id. at 14. According to Appellant, Examiner
is unable to explain . . . why it is that a person of ordinary skill
at the time of the invention would . . . go[] outside the most
preferred ranges of sucrose concentrations taught by Taylor and
Brockbank to experiment on skin within the bounds of a
broader less preferred range that includes also in large portion a
sucrose content substantially below the 25% minimum that is
now claimed.
Id. In addition, Appellant argues the data in Table 1 of the Specification
show that the 25–40% sucrose range recited in claim 1 provides
“unexpectedly good” results as compared to amounts within the broader
ranges taught in the prior art. See Appeal Br. 18 (citations omitted).

9 Appellant calculates that the “0.1 to 2.0M” range taught in Brockbank is
equivalent to “about 0.3% to 68%” and that Brockbank’s more preferable
“0.2 to 0.6M” range is equivalent to “about 7% to 20%.” Appeal Br. 8.
Examiner does not dispute Appellant’s calculations and, indeed, relies upon
them in the Answer. See Ans. 8–9 (stating Brockbank “is cited for []
teaching that sucrose can be used at concentrations up to 68%”).
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Based on the current record, we determine that Appellant has the
better position. Examiner’s rejection of claim 1 is premised on the
conclusion that it would have been obvious for a skilled artisan to select two
of the cryoprotectants (i.e., DMSO and sucrose) from the much longer list of
known cryoprotectants taught in Gabbai, combine them with culture medium
and fetal bovine serum, and then adjust the amounts of those components to
the recited ranges. The evidence Examiner relies on for the recited sucrose
range are teachings in Taylor and Brockbank regarding different solutions
comprising sucrose along with an array of other ingredients in a wide range
of amounts. See, e.g., Taylor 11:54–13:57 (describing various “exemplary”
base solutions comprising a multitude of ingredients other than sucrose);
Brockbank ¶¶ 32–33 (providing a long, non-exclusive list of cryoprotectants
to be used in combination with various sugars, including sucrose).
Appellant does not dispute that some of the ranges taught in Taylor and
Brockbank partially overlap with the sucrose range recited in claim 1. But
Examiner has not sufficiently explained why it would have been obvious for
one of ordinary skill to select those ranges from the much broader array of
solutions and ingredients described in these references for the purpose of
modifying the cryoprotectant solution in Gabbai’s method. Instead, as
Appellant urges, “[t]he Rejection presumes a guidance to use sucrose and
DMSO to increase cell viability of living skin that does not exist” in the
cited references, at least as those references are presented by Examiner. See
Appeal Br. 14.
Appellant’s argument that the results in the Specification show that
solutions containing “25–40% by weight” sucrose, as recited in claim 1,
exhibit improved results is also persuasive. See Appeal Br. 18.
Experimental Example 2 in the Specification describes a study “[t]o
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investigate the change of the cell death rate according to the difference of
sucrose concentration” in the cryoprotectant solution for “cryopreserved
allograft skin.” Spec. ¶ 29. According to the Specification, the skin samples
in this study were penetrated with cryoprotectant solutions composed of
DMSO, an animal cell culture medium, and fetal bovine serum in a 1: 4 : 5
by weight mixing ratio and varying amounts of sucrose (i.e., “5, 10, 15, 20,
25, 39, 35 and 40 wt%”) for 12 hours, frozen, and then assayed to determine
the “cell death rate.” Id. ¶¶ 22, 29. The data in Table 1 and Figure 6 of the
Specification support that skin allographs penetrated with a solution
containing 25–40% sucrose had a lower average death rate than allographs
prepared with a solution containing 5–20% sucrose. Id. ¶ 29, Fig. 6.
Examiner does not dispute that these results demonstrate that
solutions containing an amount of sucrose within the recited range provide
improved results as compared to solutions with sucrose concentrations
outside that range. Instead, Examiner faults Appellant for not “provid[ing]
any showing as to why their observed improvement would not be expected.”
Ans. 13. Such criticism is beside the point because it is the patent examiner,
not the applicant, who bears the burden to present a prima facie showing for
the rejection. In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992) (“[T]he
examiner bears the initial burden, on review of the prior art . . . of presenting
a prima facie case of unpatentability.”). As explained above, Examiner here
has not sufficiently articulated why a skilled artisan, absent improper
hindsight guided by Appellant’s disclosure, would have combined Taylor or
Brockbank’s teachings regarding a sucrose range with Gabbai’s method of
processing a skin allograft. The data in the Specification showing that the
recited sucrose range provides improved results as compared to other
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sucrose concentrations further highlights that Examiner has not presented a
sufficient prima facie case.
For these reasons, we determine that Examiner’s rejection of claim 1
as obvious over the cited prior art is not supported by the preponderance of
the evidence and, therefore, reverse. We reverse the obviousness rejections
of dependent claims 3 and 5–7 for the same reasons.

CONCLUSION
In summary:
Claims
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
1, 3, 5 103 Gabbai, Livesey,
Applegate, Taylor,
Brockbank
1, 3, 5
6, 7 103 Gabbai, Livesey,
Applegate, Taylor,
Brockbank, Wang
6, 7
Overall
Outcome
1, 3, 5–7

REVERSED