Hisatoshi Kobayashi et al.

Patent Trials and Appeals Board

Sep 11, 2019

13848738 - (D) (P.T.A.B. Sep. 11, 2019)

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.
13/848,738 03/22/2013 HISATOSHI KOBAYASHI 46311-US-599 7301
31561 7590 09/11/2019
JCIPRNET
P.O. Box 600 Taipei Guting
Taipei City, 10099
TAIWAN
EXAMINER
HILL, NICHOLAS E
ART UNIT PAPER NUMBER
1767
NOTIFICATION DATE DELIVERY MODE
09/11/2019 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):
Belinda@JCIPGROUP.COM
USA@JCIPGROUP.COM
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte HISATOSHI KOBAYASHI, DOHIKO TERADA,
MASAMI TODOKORO, AKIKO SHIMATANI, and
YUKINORI KATAOKA1
____________

Appeal 2017-011513
Application 13/848,738
Technology Center 1700
____________

Before JANET A. GONGOLA, Vice Chief Administrative Patent Judge,
ROMULO H. DELMENDO, and JAMES T. MOORE, Administrative
Patent Judges.

GONGOLA, Vice Chief Administrative Patent Judge.

DECISION ON APPEAL
Appellant files this appeal under 35 U.S.C. § 134(a) from a final
rejection of claims 1–12. We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.

1 JNC CORPORATION is listed as the Applicant and the real party in
interest. Application Data Sheet filed March 22, 2013 at 5; Appeal Brief
filed April 25, 2017 (“App. Br.”) 1.

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Application 13/848,738

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BACKGROUND
The claims on appeal are directed to a method of producing a
nano-fiber by electrospinning a solution containing a synthetic collagen and
a polymer. Specification filed March 22, 2013 (“Spec.”) ¶ 11. The synthetic
collagen is a polypeptide having a peptide fragment represented by the
formula -(Pro-Y-Gly)n- wherein Y represents hydroxyproline or proline.
Spec. ¶ 12. The Specification discloses that electrospinning is a known
method for producing nanofibers. Spec. ¶ 2. The Specification also
discloses the claimed method results in uniform and long fibers. Spec. ¶ 7.
Claim 1 is representative of the subject matter on appeal and is
reproduced below:
1. A method of producing a nano-fiber that contains a
polypeptide having a peptide fragment represented by Formula
(1):

-(Pro-Y-Gly)n- (1),

wherein Y represents a hydroxyproline or proline, and n
is an integer ranging from 5 to 9000, the producing method
comprising:

preparing a spinning solution containing the polypeptide
and a polymer, and

spinning with an electrospinning method using the
spinning solution, wherein a solvent in the spinning solution
comprises an organic solvent.

App. Br. 19 (Claims App’x)(paragraphing added).
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Independent claims 7 and 12 differ from claim 1 in that they recite
“the polymer comprises one, two or more selected from the group consisting
of natural collagen and polyvinyl alcohols,” among other features. App. Br.
19–20.
REJECTIONS ON APPEAL
1. The Examiner rejected claims 1–6 under 35 U.S.C. § 103(a) as
unpatentable over Huang,2 Shibasaki,3 and Matthews.4 Final Office Action
entered December 12, 2016 (“Final Act.”) 2–5.
2. The Examiner rejected claims 7–12 under 35 U.S.C. § 103(a) as
unpatentable over Huang, Shibasaki, Matthews, and Simpson.5 Final Act.
5–11.
Appellant states that the independent claims, 1, 7, and 12 may be
taken as representative of the claims on appeal. See Appeal Br. 5.
Accordingly, we select these claims as representative of the dependent
claims and decide this appeal based on the rejection of claims 1, 7, and 12.
37 C.F.R. § 41.37(c)(1)(iv). We combine the discussion of the rejections
that involve the same references hereinafter.

2 Huang, L. et al., Engineered collagen-PEO nanofibers and fabrics,
12 J. Biomater. Sci. Polymer Edn. 979–993 (2001) (“Huang”).
3 Shibasaki, Y. et al., Collagen-Like Polypeptide Poly(Pro-Hyp-Gly)
Conjugated with Gly-Arg-Gly-Asp-Ser and Pro-His-Ser-Arg-Asn Peptides
Enhances Cell Adhesion, Migration, and Stratification, 96 Peptide Science
302–315 (2010) (“Shibasaki”).
4 Matthews, J. A. et al., Electrospinning of Collagen Nanofibers, 3
Biomacromolecules 232–238 (2002) (“Matthews”).
5 Simpson et al., U.S. Pat. Pub. No. 2004/0037813 A1, published February
26, 2004 (“Simpson”).
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DISCUSSION
I. Obviousness of Claims 1–6 over the Combination of Huang,
Shibasaki, and Matthews
The Examiner finds that “Huang teaches a method of preparing
nanofibers by (i) preparing a solution of type I collagen and polyethylene
oxide (i.e., a polymer); and (ii) electrospinning the solution.” Final Act. 3,
citing Huang Abst. The Examiner acknowledges that Huang teaches a
spinning solution that is aqueous HCl and not an organic solvent. Id.
However, the Examiner finds “Matthews teaches that the organic solvent
1,1,1,3,3,3-hexafluoro-2-ispropanol (i.e., HFP) is the solvent of choice for
electrospinning collagen because its lower boiling point promotes the
evaporation of the solvent under conventional atmospheric conditions.” Id.,
citing Matthews 234. The Examiner also acknowledges that Huang does not
teach the claimed peptide fragment of Formula (1). Id. But the Examiner
finds that Shibasaki teaches a collagen-like synthetic peptide containing a
poly(Pro-Y-Gly)n- peptide fragment, wherein Y is hydroxyproline, and n is
equal to about 50. Id., citing Shibasaki Abst.; 306. The Examiner
determines:
[i]t would have been obvious to a person having ordinary skill
in the art at the time of the invention to have replaced the type I
collagen of Huang with the collagen-like peptide of Shibasaki,
and the motivation to have done so would have been, as
Shibasaki suggests, that poly(Pro-Hyp-Gly[])-based collagen-
like polypeptides enhance cell adhesion, migration, and
stratification, and, consequently, may be useful scaffolds for
tissue regeneration.

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Id.
Appellant presents a series of arguments in attempt to overturn the
Examiner. First, Appellant contends “Huang merely indicates that natural
collagen is soluble in acidic water . . . and can be electrospun . . . but
mentions nothing about . . . synthetic collagen.” App. Br. 7 (emphases in
original). Appellant contends that “Shibasaki mentions nothing about fiber
spinning using a syntheticcollagen . . . .” Id. (emphasis omitted). Appellant
contends that “Matthews only teaches using an organic solvent . . . as a
solvent for electrospinning a natural collagen . . . but also fails to disclose
i) whether or not a synthetic collagen could be dissolved in an organic
solvent . . . or ii) any other property of the synthetic collagen in an organic
solvent . . . .” Id. (emphases in original).
We are not persuaded by Appellant’s arguments. Appellant
erroneously argues the prior art references on an individual basis.
“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).
Here, the Examiner identified each component of the claims in the
combined prior art. Therefore, the question is whether it would have been
obvious to one of ordinary skill in the art, working with the Huang,
Matthews, and Shibasaki references before them, to apply an electrospinning
method to synthetic collagen in an organic solvent to produce nano-fibers.
In re Keller, 642 F.2d 413, 425 (CCPA 1981) (“the test [for obviousness] is
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what the combined teachings of the references would have suggested to
those of ordinary skill in the art”). We address this question below.
Second, Appellant contends “that synthetic collagen and natural
collagen have remarkably different properties” and, therefore, there
would be no reasonable expectation of success in combining the references.
App. Br. 7–8 (emphasis in original). To support this argument, Appellant
submits a Declaration describing two different experiments comparing
natural to synthetic collagen.6 Appellant contends that Experiment 1 proves
the viscosity of natural collagen varies significantly at different pHs, but the
viscosity of synthetic collagen does not vary at different pHs. App. Br. 8–9.
Appellant contends that Experiment 2 proves the triple helix structure of
natural collagen is destroyed at high temperatures, but the triple helix
structure of synthetic collagen is maintained at high temperatures. App. Br.
10–12.
We are not persuaded by Appellant’s arguments. We agree with
Appellant that natural and synthetic collagen have different physical
properties. But Appellant has not shown that these different properties
would preclude one of ordinary skill in the art from combining the
references. “Obviousness does not require absolute predictability of
success. . . . For obviousness under § 103, all that is required is a reasonable
expectation of success.” In re O’Farrell, 853 F.2d 894, 903–04 (Fed. Cir.
1988).
Moreover, because Shibasaki itself acknowledges that natural
collagen has several drawbacks such as “low thermal stability,” (Shibasaki

6 Declaration of Hideaki Fukushi, filed October 12, 2016 (“Fukushi Decl.”)
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302), Shibasaki teaches the chemical synthesis of poly(Pro-Hyp-Gly), which
forms a stable triple-helical structure at temperatures up to 80° C and does
not present the same drawbacks as natural collagen (Id. at 303). Appellant’s
argument that a skilled artisan would not consider synthetic collagen over
natural collagen, App. Br. 9, thus is not supported by the evidence of record.
Accordingly, Appellant has not provided persuasive evidence that a person
of ordinary skill in the art would not expect Shibasaki’s synthetic collagen to
be applicable to Huang’s electrospinning methods using Matthews’ organic
solvent.
Third, Appellant contends that modifying the use of natural collagen
in Huang with synthetic collagen as taught by Shibasaki draws away from
the original purpose of Huang. App. Br. 12.
We are not persuaded by Appellant’s argument. Appellant does not
identify any teaching in Huang that would have suggested that the
electrospinning method would not apply to synthetic collagen. See Syntex
(U.S.A.) LLC v. Apotex, Inc., 407 F.3d 1371, 1380 (Fed. Cir. 2005) (“a
reference will teach away when it suggests that the developments flowing
from its disclosures are unlikely to produce the objective of the applicant’s
invention”). Rather, substituting synthetic collagen into the known method
of electrospinning natural collagen would have been considered by a skilled
artisan as the “mere substitution of one element for another known in the
field,” that yields a predictable result. KSR Int’l Co. v. Teleflex Inc., 550
U.S. 398, 416 (2007).
Finally, Appellant argues that “Shibasaki teaches that in order to
enhance cell adhesion, migration and stratification, the collagen-like
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polypeptide Poly(Pro-Hyp-Gly) is conjugated with Gly-Arg-Gly-Asp-Ser
and Pro-His-Ser-Arg-Asn peptides.” App. Br. 13. Appellant argues that
combining the references without the conjugated peptide fragments is
hindsight gleaned from the instant application. Id.
We are not persuaded by Appellant’s arguments. In rejecting the
claimed invention as obvious, we find that the Examiner has taken into
account only knowledge which was within the level of ordinary skill at the
time the claimed invention was made, and has not applied improper
hindsight. In re McLaughlin, 443 F.2d 1392, 1395 (CCPA 1971) (“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 . . . such a reconstruction is proper”).
Shibasaki teaches that conjugation of peptides with natural collagen
enhance cell adhesion and differentiation. See Shibasaki 303. Appellant has
not identified any teaching in Shibasaki that conjugated peptides are
necessary to address the drawbacks of natural collagen, nor any limitation in
the claims that would necessarily exclude the conjugated peptides.
Appellant raises similar arguments to distinguish Matthews
individually. See App. Br. 13–14. In particular, Appellant argues that
Matthews only teaches using HFP to dissolve natural collagen (App. Br. 13)
and that the Fukushi Declaration establishes that synthetic collagen has
“much higher” stability than natural collagen (App. Br. 14). Therefore,
Appellant argues there is no reasonable expectation of success in combining
the references. App. Br. 14; see also Reply Brief filed September 12, 2017
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(“Reply Br.”) 1–2. Moreover, Appellant argues the Examiner has not
provided a reason for combining Matthews with Huang and Shibasaki. Id.
We are not persuaded by Appellant’s arguments. Matthews
unambiguously states “[p]reliminary experimentation identified HFP as the
solvent of choice for electrospinning collagen.” Matthews 234. Matthews’
teaching establishes a reasonable expectation of success in applying HFP as
a solvent for electrospinning various collagens, including synthetic collagen.
“A person of ordinary skill is also a person of ordinary creativity, not an
automaton.” KSR, 550 U.S. at 421.
Appellant has not identified any teaching in Matthews that suggests
HFP is unlikely to work for electrospinning synthetic collagen. Appellant’s
evidence that natural and synthetic collagen dissolve differently in aqueous
solutions of different pHs does not outweigh the Examiner’s showing that a
person of ordinary skill in the art would have had a reasonable expectation
of success in using HFP as an electrospinning solvent for synthetic collagen.
Accordingly, the preponderance of evidence supports the Examiner’s
determination that claims 1–6 would have been obvious over the
combination of Huang, Shibasaki, and Matthews, and we affirm the
Examiner’s rejection.
II. Obviousness of Claims 7–12 over Huang, Shibasaki, Matthews,
and Simpson
The Examiner finds that the combination of Huang, Shibasaki, and
Matthews teaches a method of producing a nano-fiber by electrospinning a
solution of synthetic collagen and a polymer in an organic solvent. Final
Act. 6–7. The Examiner acknowledges that “Huang does not teach that the
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spinning solution contains a polymer that is natural collagen or a polyvinyl
alcohol.” Id. at 7. The Examiner cites Simpson for teaching “both
polyethylene oxide and polyvinyl alcohol are suitable synthetic materials
that may be combined with collagen in electrospinning collagen fibers.” Id.,
citing Simpson ¶¶ 92, 96, and 99. The Examiner finds the motivation to
substitute polyvinyl alcohol for polyethylene oxide as taught by Huang is
that the prior art teaches the two polymers are equivalents for the same
purpose. Id.
Appellant advances that “no Example of Simpson used polyethylene
oxide or polyvinyl alcohol” and that “polyvinyl alcohol is not even a
preferred polymer of Simpson.” App. Br. 16.
We do not find Appellant’s argument persuasive. “[A]ll disclosures
of the prior art, including unpreferred embodiments, must be considered.”
In re Lamberti, 545 F.2d 747, 750 (CCPA 1976). Here, Simpson teaches
that electroprocessed collagen may be combined with other materials,
including synthetic materials such as poly(vinyl alcohol) and poly(ethylene
oxide). Simpson ¶ 99. That Simpson does not list polyvinyl alcohol as a
preferred synthetic material does not demonstrate nonobviousness of the
claims.
Appellant also argues that the claimed method provides the
unexpected effect of “a uniform and long fibrous nano-fiber.” App. Br. 16,
citing Spec. ¶¶ 7, 8, 36, 41, and 42.
We do not find Appellant’s argument persuasive. Both Huang (Abst.)
and Simpson (¶ 134) teach electrospun collagen nanofibers having diameters
of 100–150 nm, which qualify as “uniform and long.” See Spec.
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¶ 33. Indeed, Huang states: “Uniform fibers with a diameter range of 100–
150 nm were produced.” Huang Abst. Moreover, Appellant does not
submit any evidence that the resulting nano-fibers were unexpected. “[I]t is
well settled that unexpected results must be established by factual evidence.
Mere argument or conclusory statements in the specification does not
suffice.” In re Geisler, 116 F.3d 1465, 1470 (Fed. Cir. 1997). Moreover,
we do not see such a limitation contained within the claims.
Accordingly, the preponderance of evidence supports the Examiner’s
determination that claims 7–12 would have been obvious over Huang,
Shibasaki, Matthews, and Simpson, and we affirm the Examiner’s rejection.
SUMMARY
In summary, we affirm the Examiner’s rejections of claims 1–6 under
35 U.S.C. § 103(a) as unpatentable over Huang, Shibasaki, and Matthews.
We affirm the Examiner’s rejections of claims 7–12 under 35 U.S.C.
§ 103(a) as unpatentable over Huang, Shibasaki, Matthews, and Simpson.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(1).

AFFIRMED