S-BIOMEDICS

Patent Trials and Appeals Board

Dec 2, 2021

2021001633 (P.T.A.B. Dec. 2, 2021)

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.
15/322,003 12/23/2016 Dong Wook KIM 6680L-000190-US-NP 4900
28997 7590 12/02/2021
Harness Dickey (St. Louis)
7700 Bonhomme, Suite 400
St. Louis, MO 63105
EXAMINER
FONTAINHAS, AURORA M
ART UNIT PAPER NUMBER
1649
NOTIFICATION DATE DELIVERY MODE
12/02/2021 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):
bkamer@hdp.com
stldocket@hdp.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte DONG WOOK KIM and HAN SOO KIM
Appeal 2021-001633
Application 15/322,003
Technology Center 1600
Before JEFFREY N. FREDMAN, JOHN E. SCHNEIDER, and RACHEL
H. TOWNSEND, Administrative Patent Judges.
SCHNEIDER, Administrative Patent Judge.
DECISION ON APPEAL
STATEMENT OF THE CASE
Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from the
Examiner’s decision to reject claims 19, 21–23, 37, 39–41, and 43.2 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(a). Appellant identifies the real party in interest as S-Biomedics.
Appeal Br. 3.
2 Claims 20, 25–32, 35, and 36 are pending in the application but have been
withdrawn from consideration. Final Act. 2.
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CLAIMED SUBJECT MATTER
The claims are directed to a method for treating ischemic diseases or
neuroinflammatory diseases using neural progenitor cells. Claim 19,
reproduced below, is illustrative of the claimed subject matter:
19. A method for treating stroke the method comprising
administering a composition comprising poly-sialylated neural
cell adhesion molecule (PSA-NCAM)-positive neural precursor
cells as an active ingredient to a subject in need thereof,
wherein the PSA-NCAM-positive neural precursor cells
are separated from neural rosettes differentiated from
pluripotent stem cells, using an anti-PSA-NCAM-antibody, and
wherein the pluripotent stem cells are embryonic stem
cells or induced pluripotent stem cells (IPSCs).
REFERENCES
The prior art relied upon by the Examiner is:
Name Reference Date
Dae-Sung Kim et al., Highly Pure and Expandable PSA-NCAM-Positive
Neural Precursors from Human ESC and iPSC-Derived Neural Rosettes,
7 PLoS ONE e39715 (2012)
Serena Barral et al., Efficient neuronal in vitro and in vivo differentiation
after immunomagnetic purification of mESC derived neuronal precursors,
10 Stem Cell Res. 133–146 (2013)
Da-Jeong Chang et al., Therapeutic Potential of Human Induced
Pluripotent Stem Cells in Experimental Stroke, 22 Cell Transplantation
1427–1440 (2013)

REJECTION
The Examiner has rejected claims 19, 21–23, 37, 39–41, and 43 under
35 U.S.C. § 103 as unpatentable over Chang in view of Kim and Barral.

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OPINION
Issue
The issue with respect to this rejection is whether a preponderance of
the evidence supports the Examiner’s conclusion that the subject matter of
claims 19, 21–23, 37, 39–41, and 43 would have been obvious to one of
ordinary skill in the art at the time the invention was made over Chang in
combination with Kim and Barral.
The Examiner finds Chang teaches transplanting stem-cell derived
neural precursor cells (“NPCs”) to restore neural tissues and circuitry
thereby treating stroke. Final Act. 3–4. The Examiner finds Chang teaches
that the NPCs are obtained from induced pluripotent stem cells which
include embryonic stem cells that were isolated from rosette-like structures.
Id. at 4. The Examiner finds Chang teaches that transplantation of NPCs
promotes angiogenesis. Id. The Examiner finds
Chang teaches looking to PSA-NCAM marker as a way to
identify endogenous neurogenesis and cell migration in the
SVZ of stroke induce brain (see page 1438, 2nd column, 1st
paragraph, page 1436, bottom of 1st column and top of 2nd
column) but does not teach using PSA-NCAM positive NPCs
as required in instant claims 19 and new claim 43.

Id.
The Examiner finds Kim teaches producing PSA-NCAM positive
NPCs from human pluripotent stem cells for replacement therapies of the
nervous system. Id. at 5. The Examiner finds “Kim teaches using a PSA-
NCAM antibody to isolate PSA-NCAM positive cells from expanded
neuronal rosettes cells.” Id. The Examiner finds “Kim teaches that the PSA-
NCAM positive NPCs are able to integrate into the adult mammalian brain,
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have full capacity of neural differentiation potential in vivo and have a
significantly lower possibility of neural outgrowth when compare[d] to
unsorted and non-propagated neural rosette cells.” Id. The Examiner finds
“Kim teaches using these PSA-NCAM positive NPCs as reliable cell source
for future cell replacement therapy. Kim does not specifically teach using
these specific cells for the treatment of ischemic stroke.” Id.
The Examiner finds Barral teaches a method for isolating PSA-
NCAM positive NPCs from embryonic stem cells and derived pluripotent
cells (iPSCs) and their use for transplantation and cell replacement therapy.
Id. at 6. The Examiner finds Barral teaches “using PSA-NCAM antibodies to
help identify and isolate the PSA-NCAM positive cells.” Id. The Examiner
finds Barral “teaches that these PSA-NCAM cells have the potential for
promoting brain repair such as lesion models of ischemia and brain trauma
and teaches the administration of these sorted cells into the forebrain.” Id.
The Examiner concludes
It would have been prima facie obvious to the person of
ordinary skill in the art to arrive at the claimed invention from
the disclosures of Chang, Kim and Barral. The person of
ordinary skill in the art would have been motivated to make and
use the invention as claimed because one of ordinary skill in the
art would want to administer a cell population able to produce
neuronal cells to replace the lost cells due to ischemic stroke
without fear of leading to unwanted tumorigenesis. Chang
teaches that one of the issues with NPCs is the potential of
tumorigenesis (see page 1433, 1st column, 2nd paragraph) as
does Kim (see page 2, 1st column) and Barral (see page 143, 1st
column). Further, one would be motivated to use the cells
taught by Kim and Barral in the method of treatment for
ischemic stroke taught by Chang since these cells are capable of
integrating into the cortex and produce neurons as taught by
Barral (see page 140, 2nd column, 2nd paragraph). One of
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ordinary skill would be motivated to use these PSA-NCAM
positive cells to treat cerebrovascular ischemic injury such as
stroke as taught by Chang since Barral teaches that these PSA-
NCAM cells have the potential for promoting brain repair such
as lesion models of ischemia and brain trauma and teaches the
administration of these sorted cells into the forebrain (see page
134, 2nd column, 1st paragraph and 2nd paragraph). Further,
one of ordinary skill in the art would be motivated to administer
the sorted PSA-NCAM cells to infarct site as in instant claim 39
since one would want to administer the treatment of
replacement cells close to the area of cell loss to reduce the
amount of migration necessary to reach the site of injury and
Barral has already shown that these presorted cell are capable of
integrating into the cortex/forebrain of an animal model.
Finally, one of ordinary skill in the art would have a reasonable
expectation of increasing vascularization at the site of the lesion
in a stroke patient since NPCs also promotes angiogenesis (see
page 1438, 1st column, bottom of 1st paragraph). Accordingly,
the cumulative reference teachings render obvious the claimed
method. The person of ordinary skill in the art would have had
a reasonable expectation of success based on the cumulative
disclosures of these prior art references.

Id. at 7–8.
Appellant contends that while Chang teaches that the NPCs used have
a therapeutic potential, the equivocal language of Chang does not
specifically teach that the NPCs can be used to treat stroke. Appeal Br. 6.
Appellant also contends that Chang uses different NPCs than those claimed.
Id.
Appellant contends that Barral also does not teach or suggest using
NPCs to treat stroke let alone the use of PSA-NCAM-positive NPCs to treat
stroke. Id.
With respect to claim 43, Appellant contends that Chang suggests the
NPCs can promote angiogenesis but that angiogenesis is not the same as
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vascularization as recited in claim 43. Id. at 7. Appellant argues that the
Examiner has improperly equated angiogenesis with vascularization and has
arrived at an improper finding of obviousness. Id.
Appellant contends that one skilled in the art would not have a
reasonable expectation of success in combining the references as neither
Chang nor Barral shows any likelihood that PSA-NCAM-positive NPCs can
be used to treat stroke. Id.
Appellant contends that there is no motivation to combine the
teachings of Chang and Kim. Id. at 8. Appellant argues that the references
offer no guidance as to why one skilled in the art would replace the NPCs of
Chang with the NPCs of Kim. Id. Appellant contends that the Examiner has
not set forth a sufficient justification for modifying the method of Chang to
use the cells of Kim. Id.
Finally, Appellant contends that the rejection is based on the
impermissible use of hindsight. Id. at 9. Appellant contends that none of the
references teach or suggest the use of PSA-NCAM-positive NPCs to treat
stoke and only by using the present Specification as a road map would one
skilled in the art arrive at the presently claimed invention. Id. at 9–10.
Principles of Law
“[T]he examiner bears the initial burden, on review of the prior art or
on any other ground, of presenting a prima facie case of unpatentability. If
that burden is met, the burden of coming forward with evidence or argument
shifts to the applicant.” In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992).
“The factual predicates underlying an obviousness determination
include the scope and content of the prior art, the differences between the
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prior art and the claimed invention, and the level of ordinary skill in the art.”
In re Rouffet, 149 F.3d 1350, 1355 (Fed. Cir. 1998).
Analysis
We adopt the Examiner’s findings of fact, reasoning on scope and
content of the prior art, and conclusions set out in the Final Action and
Answer regarding this rejection. We find the Examiner has established a
prima facie showing that the subject matter of the claims would have been
obvious over Chang combined with Kim and Barral to a person of ordinary
skill in the art at the time the invention was made. Appellant has not
produced evidence showing, or persuasively argued, that the Examiner’s
determinations on obviousness are incorrect. Only those arguments made by
Appellant in the brief have been considered in this Decision. Arguments not
presented in the brief are waived. See 37 C.F.R. § 41.37(c)(1)(iv) (2015).
We have identified claim 19 as representative; therefore, all claims, except
for claim 43 which was argued separately, fall with claim 19. We address
Appellant’s arguments below.
Appellant contends that Chang does not teach or suggest the use of
NPCs to treat stroke but only states that work provides encouraging evidence
of potential therapeutic value. Appeal Br. 6. Appellant also contends that
Chang suggests the use of cells different than those recited in the claims. Id.
We are not persuaded by these arguments.
We agree with the Examiner that Chang clearly teaches the use of
NPCs to treat stroke. Ans. 8. Chang states “[o]ur results demonstrate that
iPSC-derived NPCs are effective cells for the treatment of stroke.” Chang
Abstr. Chang also states that the study of the rodent model of middle
cerebral artery occlusion model studied where iPSC-derived NPCs were
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implanted, demonstrated that iPSC-derived NPCs “show significant
reduction in inflammation, gliosis, and apoptosis, as well as significant
contribution to the endogenous neurogenesis, implying that iPSC-derived
NPCs have the unique properties of treating stroke using all the several
modes of action as described above.” Chang 1428.
With respect to Chang using different cells than those recited in the
claims, the Examiner noted this difference and cites to Kim for teaching the
use of PSA-NCAM-positive NPCs. Final Act. 4–5. Appellant’s argument is
an attack on the teachings of the individual reference and fails to address the
combined teachings of the references. “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).
Appellant contends that Barral also does not suggest the clinical use
of NPCs to treat stroke. Appeal Br. 7. Appellant contends that Barral
suggests that if NPCs could be used in humans, it might represent a
preferred strategy for exploring future therapeutic applications. Id. Appellant
contends that Barral’s equivocal statements would not lead one skilled in the
art to the claimed invention. Id.
We remain unpersuaded by Appellant’s argument. As discussed
above, Chang teaches the use of NPCs to treat stroke. It is the combined
teaching of the references that serves as the basis of the rejection, not the
individual references.
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Appellant contends that one skilled in the art would not have a
reasonable expectation of success as the Examiner mischaracterizes the
teachings of Chang and Barral. Appeal Br. 7. Appellant contends that the
Examiner improperly transitions from the preclinical experiments reported
in the references to an expectation of success without presenting any
guidance from the art or additional reasoning. Id. In support of this argument
Appellant cites to OSI Pharmaceuticals v. Apotex Inc., 939 F.3d 1375, 1384
(Fed. Cir. 2019) where our reviewing court found the disclosure of an
antibody, in the absence of any clinical, preclinical animal, or preclinical in
vitro data of the antibody’s effect on lung cancer, did not render a method of
using the antibody to treat lung cancer obvious. Id.
We have considered Appellant’s argument and are not persuaded that
the rejection is in error. The present claims only call for the treatment of
stroke, and are not limited to treatment of humans. Appeal Br. 12 (Claims
App.). Chang states the transplantation of the NPCs in animals showed
“significant reduction of stroke-induced inflammatory response, gliosis and
apoptosis, and the contribution to the endogenous neurogenesis.” Chang
Abstr. Thus, Chang presents animal data to support the conclusion that
NPCs are effective for the treatment of stroke.
The facts in the present case are distinguishable from those in OSI. In
OSI, the reference relied on failed “to disclose any in vitro or in vivo efficacy
data for erlotinib or otherwise suggest the use of erlotinib to treat NSCLC.”
OSI, 939 F.3d at 1384. This is in direct contrast to the present case where
Chang provides in vivo animal data showing the efficacy of NPCs to treat
stroke. Chang Abstr.; 1433–1438. Chang’s animal data in a relevant animal
model would have provided one of ordinary skill in the art with a reason to
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expect to be able to treat stroke. Cf. Edwards Lifesciences AG v. CoreValve,
Inc., 699 F.3d 1305, 1309 (Fed. Cir. 2012) ( “[I]t has long been recognized
that when experimentation on human subjects is inappropriate, as in the
testing and development of drugs and medical devices, the enablement
requirement may be met by animal tests or in vitro data.”)
Appellant contends that the Examiner has failed to adequately set
forth a motivation to modify the teachings of Chang with those of Kim.
Appellant contends that while the references teach that the NPCs of Kim can
be readily integrated into the cortex and produce neurons, that is insufficient
to lead one skilled in the art to use the NPCs of Kim in the method of Chang
let alone to treat stroke. Appeal Br. 8–9. This argument is also unpersuasive.
Kim teaches that the technique disclosed therein “suggests that PSA-
NCAM-targeted cell isolation enables enrichment of a homogenous
population of primitive NPCs from hPSCs and minimizes safety concerns
after transplantation. This provides a promising cell source for practical
applications, such as drug screening and regenerative medicine for central
nervous system (CNS) diseases.” Kim 2. Barral teaches that PSA-NCAM
cells have the potential for promoting brain repair such as lesion models of
ischemia and brain trauma and teaches the administration of these sorted
cells into the forebrain. Barral 134. Chang teaches that NPCs can be
effective in treating stroke. We find that the combined teachings of the
references would have motivated one skilled in the art to use the NPCs of
Kim in the method of Chang given Kim’s teaching of a homogenous
population of NPCs that have minimal safety concerns.
Appellant contends that the rejection relies on the improper use of
hindsight in that the teachings of Chang and Barral are speculative regarding
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the clinical usefulness of NPCs and Kim is silent with respect to any clinical
effect. Appeal Br. 9–10. Appellant contends that only using the present
Specification as a guide would one skilled in the art combine the teachings
of the references to produce the claimed invention. Id.
We have considered Appellant’s argument and are not persuaded that
the Examiner resorted to the improper use of hindsight.
“Any judgment on obviousness is in a sense necessarily a
reconstruction based upon hindsight reasoning, but so long as it takes into
account only knowledge which was within the level of ordinary skill at the
time the claimed invention was made and does not include knowledge
gleaned only from applicant’s disclosure, such a reconstruction is proper.”
In re McLaughlin, 443 F.2d 1392, 1395 (CCPA 1971).
In the present case, Chang specifically teaches the use of NPCs to
treat stroke. Chang Abstr. Kim teaches the advantages of using PSA-
NCAM-positive NPCs and that they can be used as “regenerative medicine
for central nervous system (CNS) diseases.” Kim 2. Thus, the references
themselves suggest the use of the NPCs of Kim in the method of Chang to
treat stroke. Appellant does not point to nor do we discern any specific
knowledge that is gleaned only from Appellant’s disclosure.
Finally, with respect to claim 43, Appellant contends that the
Examiner improperly equates angiogenesis with vascularization. Appeal Br.
7. Appellant contends that vascularization and angiogenesis are two different
process with angiogenesis focused on the protrusion of and outgrowth of
capillaries whereas vascularization is directed to formation of new blood
vessels. Id. Appellant contends that Chang only teaches the use of NPCs to
stimulate angiogenesis and not vascularization as recited in claim 43.
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Again, we find this argument unpersuasive. As the Examiner points
out, Appellant offers no evidence to support its contention that angiogenesis
and vascularization are separate processes but only offers attorney argument.
Ans. 10. “Attorney’s argument in a brief cannot take the place of evidence.”
In re Pearson, 494 F.2d 1399, 1405 (CCPA 1974).
Conclusion
Based on the foregoing we conclude that a preponderance of the
evidence supports the Examiner’s conclusion that the subject matter of
claims 19, 21–23, 37, 39–41, and 43 would have been obvious to one of
ordinary skill in the art at the time the invention was made over Chang in
combination with Kim and Barral.
CONCLUSION
The Examiner’s rejection is affirmed.
More specifically, the rejection of claims 19, 21–23, 37, 39–41, and
43 under 35 U.S.C. § 103 as unpatentable over Chang in view of Kim and
Barral is affirmed.
DECISION SUMMARY
In summary:
Claims
Rejected
35 U.S.C.
§
Reference(s)/Basis Affirmed Reversed
19, 21–23,
37, 39–41,
43
103 Chang, Kim,
Barral
19, 21–23,
37, 39–41,
43

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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