Nur, Israel et al.

Patent Trials and Appeals Board

Apr 7, 2020

12665810 - (D) (P.T.A.B. Apr. 7, 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.
12/665,810 04/27/2010 Israel Nur ETH5481USPCT 4023
27777 7590 04/07/2020
JOSEPH F. SHIRTZ
JOHNSON & JOHNSON
ONE JOHNSON & JOHNSON PLAZA
NEW BRUNSWICK, NJ 08933-7003
EXAMINER
KIM, TAEYOON
ART UNIT PAPER NUMBER
1632
NOTIFICATION DATE DELIVERY MODE
04/07/2020 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):
jnjuspatent@corus.jnj.com
lhowd@its.jnj.com
pair_jnj@firsttofile.com
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte ISRAEL NUR, ROBERTO MEIDLER, and LILIANA BAR
Appeal 2019-003265
Application 12/665,810
Technology Center 1600
Before TAWEN CHANG, TIMOTHY G. MAJORS, and
MICHAEL A. VALEK, Administrative Patent Judges.
CHANG, Administrative Patent Judge.
DECISION ON APPEAL
Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from the
Examiner’s decision to reject claims 1, 4, 16, 64, 69, 72, 73, 75–81. 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 party in interest as Omrix
Biopharmaceuticals, LTD. Appeal Br. 3.
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BACKGROUND
According to the Specification,
[f]ibrin glue is formed by an enzymatic reaction involving inter
alia, fibrinogen, thrombin and Factor XIII. The thrombin
converts the fibrinogen to fibrin by enzymatic action at a rate
determined by the concentration of thrombin. Factor XIII[] is
typically present in the fibrinogen component of the glue and is
an enzyme of the blood coagulation system that cross-links and
stabilizes the fibrin clot.
Spec. 1:14–18.
Further according to the Specification,
[f]ibrin glues are used increasingly in surgery to reduce
bleeding, and adhesions, to sealing or filling surfaces and/or
improve wound healing. The up-to-date fibrin glue
formulations are colorless; therefore applying the preparation to
the oozing site remains difficult to control. Addition of a
visualization agent improves the application targeting qualities
of the fibrin glue, e.g. simplifies locating the application area,
enables the user to asses[s] the thickness of the applied material
and improves the visibility of the applied material. However, it
was found . . . that . . . increased concentrations of visualization
agents . . . affects the activity of thrombin.
Also, it was found according to the invention that
different visualization agents affected differently thrombin
clotting activity or clot formation.
. . . .
Advantageously, according to the invention the
visualization agent is added to the fibrin glue or a component
thereof at a concentration that is low enough to be
enzymatically-permissive but which is sufficient to clearly stain
the application site in a manner that the area can be located, the
thickness of the applied material can be assessed and/or the
applied material can be distinguished.
Id. at 3:8–26 (formatting added).
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CLAIMED SUBJECT MATTER
The claims are directed to a dyed fibrin film on a tissue surface or a
fibrin glue formulation. Claim 1 is illustrative:
1. A dyed fibrin film on a tissue surface from a solution
comprising: fibrin, thrombin, a visualization agent and water,
wherein said visualization agent is methylene blue or indigo
carmine; wherein the concentration of the visualization agent in
the solution is in the range of 0.005 to 0.025% for methylene
blue and 0.005 to 0.01% for indigo carmine, wherein the
solution comprises a costabilizer; and wherein said thrombin in
the solution retains more than 90% clotting activity in-the
presence of the visualization agent.

REJECTION(S)
Claims 1, 4, 16, 64, 69, 72–73 and 75–81 are rejected under 35 U.S.C.
§ 103(a) as being unpatentable over Sterk,2 Pathak,3 the Material Safety
Data Sheet (MSDS) for methylene blue,4 and Tse.5

DISCUSSION
A. Issue
The Examiner finds that Sterk teaches almost all of the limitations of
claim 1, except that it does not explicitly teach a dyed fibrin “film,” the
concentration of the visualization agent, and the limitation regarding

2 Sterk, US 2005/0049178 A1, published Mar. 3, 2005.
3 Pathak et al., US 7,009,034 B2, issued Mar. 7, 2006.
4 Science Lab.com, Material Safety Data Sheet: Methylene Blue MSDS
(2012).
5 Tse, US 5,792,835, issued Aug. 11, 1998.
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“thrombin . . . retain[ing] more than 90% clotting activity in the presence of
the visualization agent.” Ans. 4, 6.
With regard to the limitation of a fibrin “film,” the Examiner finds
that Sterk’s “mixed solution of fibrinogen . . . and . . . thrombin . . . would
form fibrin clots, [which] when applied onto a target surface . . . would
inherently form a film on the surface after polymerization/crosslinking.” Id.
at 4. The Examiner also finds that Pathak teaches that “polymeric hydrogels
such as fibrin glue can be applied as a thin coating or film on a tissue.” Id.
The Examiner concludes that, therefore, it would have been obvious to a
skilled artisan that the “fibrin glue/clot” taught in Sterk “can be a thin
coating or [in] film form.” Id.
With regard to the limitations relating to the concentration of the
visualization agent, the Examiner finds that Pathak teaches “the use of
methylene blue as biocompatible visualization agents for synthetic polymers
including fibrin glue, and the concentration of the visualization agents in the
final reactive precursor species mix more than 0.05 mg/ml (i.e. 0.005%),
preferably at 0.1 to 4 mg/ml (i.e. 0.01 % - 0.4%).” Ans. 5. The Examiner
concludes that “[i]t would have been obvious to one skilled in the art [to]
modify the concentration of the dye in the thrombin solution of Sterk in
order to obtain desired visibility of the glue after mixing with the fibrinogen
solution based on the teaching of Pathak . . . by routine experimentations.”
Id. at 5–6.
Finally, “[w]ith regard to the limitation directed to the thrombin in the
solution retaining more than 90% clotting activity in the presence of the
visualization agent,” the Examiner finds that limitation is inherently met by
the composition suggested by the composition of Sterk and Pathak, because
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the limitation “is interpreted . . . as a result obtainable when the claimed
concentration of the dye (visualization agent) in the claimed product is
within the claimed range.” Id. at 6.
Appellant contends that Sterk is not relevant prior art. Appeal Br. 5.
Appellant further contends that Sterk and Pathak are not related and that
they are not combinable in the manner suggested in the rejection. Id. at 6.
Finally, Appellant contends that the subject matter of the claims exhibits
unexpected results. Id. at 7.
Appellant does not separately argue the claims. We therefore focus
our analysis on claim 1 as representative. The issues with respect to this
rejection are (1) whether a preponderance of evidence supports the
Examiner’s conclusion that a skilled artisan would have had reason to
combine Sterk and Pathak to arrive at the subject matter of claim 1, with a
reasonable expectation of success, and, if so, (2) whether Appellant has
provided evidence of unexpected results that, when considered together with
the evidence of obviousness, shows claim 1 to be non-obvious.
B. Findings of Fact
1. Sterk teaches that “[f]ibrin glues have . . . proven useful as
agents for the occlusion of vessels” but that “the use of conventional fibrin
glue in oncology surgery has the disadvantage that . . . it has been very
difficult or impossible to distinguish between the diseased tissue to be
removed and the healthy tissue.” Sterk ¶ 4.
2. Sterk teaches “an agent for occluding blood vessels”
comprising at least “an agent for bringing about a vascular occlusion and a
physiologically acceptable dye,” which stains the occluded blood vessels
and “allows a safe distinction between healthy and diseased tissue and
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[which] can therefore be used advantageously during the surgical removal of
the diseased tissue.” Id. at Abstract, ¶¶ 5–6, 8; see also id. ¶ 52.
3. Sterk teaches that “[e]specially preferred is an agent that
comprises a liquid fibrinogen solution to effect the occlusion of the vessel
and can be used in cooperation with a liquid thrombin preparation.” Id. ¶ 6.
4. Sterk teaches that the tissue glue of the invention “can contain
an added preparation containing the blood coagulation factor XIII” or have
“the blood coagulation factor XIII [mixed] into the fibrinogen preparation
from the beginning.” Id. ¶ 13. The Examiner finds, and Appellant does not
dispute, that blood coagulation factor XIII is “a catalyst capable of inducing
crosslinking of fibrin.” Ans. 4.
5. Sterk teaches that “[t]he fibrin glue usable in accordance with
the invention is preferably comprised of a stabilized, liquid fibrinogen- and a
liquid thrombin preparation.” Sterk ¶ 12.
6. Sterk teaches that its fibrinogen preparation can comprise,
among other things, one or more amino acids as stabilizers. Id. ¶ 16.
7. Sterk teaches that examples of suitable dyes include methylene
blue. Id. ¶ 12.
8. Sterk teaches that the dye is “added to one of the two
preparations, generally to the thrombin preparation.” Id. ¶ 7.
9. Pathak teaches that “[a]lmost every surgical treatment carries a
risk that bodily tissue exposed during the course of the surgery will adhere to
each other, a condition termed an adhesion,” and that “[o]ne approach to the
treatment of adhesions has been to coat surgically exposed tissues with a gel
before closing the surgical site.” Pathak 1:30–32, 39–41.
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10. Pathak teaches that “polymers [may] be added to the patient ‘in
situ’ in a solution and then chemically reacted inside the patient so that the
polymers form covalent crosslinks to create a polymer network,” and that
“[t]his approach lets the polymer be formed in a way that closely conforms
to the shape of the tissues in the body.” Id. at 1:44–51.
11. Pathak teaches that “[p]olymeric hydrogels, for example, fibrin
glue, . . . are essentially colorless” and that “[t]his problem is often even
more acute when the hydrogel is applied as a coating on a tissue because
tissue coatings conventionally are thin,” and “[t]he resulting colorless
solution or film is therefore difficult to visualize.” Id. at 2:4–10.
12. Pathak teaches including visualization agents with the
biocompatible crosslinked polymers used for, among other things,
prevention of post-operative adhesions, wound dressings and surgical
sealants. Id. at Abstract, see also id. at 3:46–51 (describing uses of
biocompatible crosslinked polymers of the invention).
13. Pathak teaches that “use of color in biocompatible crosslinked
polymers . . . greatly improves their performance in a surgical environment,”
and “the better visibility available with the use of color also permits efficient
use of materials and avoids wastage.” Id. at 2:18–24; see also id. at 4:60–
65, 5:26–27 (explaining that “use of a visualization agent is especially
preferred when a hydrogel is used to coat a substrate”).
14. Pathak teaches “[a]n embodiment of [its] invention [that] is a
hydrogel for use on a substrate such as a patient’s tissue,” where “[t]he
hydrogel coats the tissue and forms a coating” and “has water, a
biocompatible visualization agent, and reactive hydrophilic polymers that
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form a crosslinked hydrogel after contact with the tissue.” Id. at 2:25–30;
see also id. at 5:37–38 (“A preferred substrate is a tissue of a patient.”).
15. Pathak teaches an embodiment that is “a hydrogel that is coated
onto a tissue and has a maximum thickness of between 0.1 to 10.0 mm.” Id.
at 2:44–46.
16. Pathak teaches that “[t]he hydrophilic polymers may be natural
polymers, for example proteins e.g., . . . fibrinogen . . . and fibrin.” Id. at
2:37–39; see also id. at 6:30–33, 26:14–25 (teaching fibrin glue or fibrin
sealant as crosslinked biodegradable hydrogel networks that may be used for
drug delivery in accordance with the invention), 40:3–5 (claim 2).
17. Pathak teaches that “[p]referred biocompatible visualization
agents are FD&C Blue #1, #2, #3, D&C Green #6, and methylene blue.” Id.
at 2:47–48; see also id. at 6:57–58, 10:58–60.
18. Pathak teaches that “[t]he preferred color [of the visualization
agent] is green or blue because it has better visibility in presence of blood or
on a pink or white tissue background.” Id. at 10:58–60; see also id. at
11:24–27.
19. Pathak teaches that the visualization agents “are preferably
present in the final electrophilic-nucleophilic reactive precursor species mix
at a concentration of more than 0.05 mg/ml and preferably . . . at least 0.1 to
about 12 mg/ml, and more preferably . . . 0.1 to 4.0 mg/ml.” Id. at 6:59–65.
Pathak teaches that “[t]hese concentration ranges were found to give a color
to the hydrogel that was desirable without interfering with crosslinking times
(as measured by the time for the reactive precursor species to gel).” Id. at
6:65–7:2.
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20. Pathak further teaches that “[t]he visualization agent may be
used in small quantities, preferably less than 1% weight/volume, more
preferably less than 0.01% weight/volume and most preferably less than
0.001% weight/volume concentration.” Id. at 11:1–4.
C. Analysis
Unless otherwise noted, we adopt the Examiner’s findings of fact and
reasoning regarding the Examiner’s rejection of claim 1 under 35 U.S.C.
§ 103(a) (Final Act. 4–7, 9–10; Ans. 3–6, 8–15) and agree that claim 1 is
obvious over Sterk, Pathak, the Material Safety Data Sheet (MSDS) for
methylene blue, and Tse. Only those arguments timely made by Appellant
in the briefs have been considered; arguments not so presented in the briefs
are waived. See 37 C.F.R. § 41.37(c)(1)(iv) (2017); see also Ex parte
Borden, 93 USPQ2d 1473, 1474 (BPAI 2010) (informative) (“Any bases for
asserting error, whether factual or legal, that are not raised in the principal
brief are waived.”). We address Appellant’s arguments below.
Appellant argues that Sterk is not relevant prior art. Appellant first
argues that Sterk describes agents for occlusion of blood vessels and that the
components of these occlusion agents are thus not provided onto tissue as a
film as recited in claim 1. Appeal Br. 5.
We are not persuaded. Two criteria have evolved for determining
whether prior art is analogous and thus may be relied on as a basis for
rejection of a claim: “(1) whether the art is from the same field of endeavor,
regardless of the problem addressed, and (2) if the reference is not within the
field of the inventor’s endeavor, whether the reference still is reasonably
pertinent to the particular problem with which the inventor is involved.” In
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re Clay, 966 F.2d 656, 658–59 (Fed. Cir. 1992). Sterk satisfies both of these
criteria.
First, the Specification describes the field of the claimed invention as
“a proteolytic enzyme composition which is capable of forming fibrin when
it reacts with fibrinogen, a fibrin-glue kit and a fibrin-glue formulation
comprising an enzymatically-permissible concentration of a visualization
agent.” Spec. 1:6–8. Sterk similarly relates to a composition comprising an
agent for bringing about a vascular occlusion, such as fibrin glue, and a
visualization agent (i.e., dye). FF1–FF4, FF7, FF8.
Second, the Specification describes the problem allegedly solved by
the claimed invention as determining a concentration of a visualization agent
to be “added to the fibrin glue . . . that is low enough to be enzymatically-
permissive but . . . sufficient to clearly stain the application site in a manner
that the area can be located, the thickness of the applied material can be
assessed and/or the applied material can be distinguished.” Spec. 3:8–26.
Sterk, which deals among other things with adding a dye to occlusion agent
such as fibrin/fibrinogen so as to stain the occluded blood vessel and
distinguish between healthy and diseased tissue, is reasonably pertinent to
the same problem. See FF1–FF2.
Appellant further argues that thrombin is an optional component in
Sterk’s occlusion agent and that, “[h]ence, Sterk did not need to consider the
potential interaction of dye and thrombin activity with respect to
fibrinogen.” Appeal Br. 5. Appellant contends that “[o]ne skilled in the art
upon viewing Sterk could not foresee that a particular dye type and
concentration were critical for visibility and reactivity” and that,
“[c]onsequently, one skilled in the art would not have started with Sterk as
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relevant prior art for production of fibrin film and fibrin glue formulations,
each having (fibrin)ogen, thrombin and a dye.” Id. at 5–6.
We are not persuaded. First, Sterk describes the combination of
fibrinogen and thrombin as “especially preferred” and specifically teaches
the addition of the dye to the thrombin preparation. FF3, FF8. Thus, we
disagree that Sterk would not have considered the potential interaction of
dye and thrombin activity.
Second, “[i]t is well settled that a prior art reference is relevant for all
that it teaches to those of ordinary skill in the art,” In re Fritch, 972 F.2d
1260, 1264 (Fed. Cir. 1992), and, “[i]n determining whether the subject
matter of a patent claim is obvious, neither the particular motivation nor the
avowed purpose of the patentee controls.” KSR Int’l Co. v. Teleflex Inc.,
550 U.S. 398, 419 (2007). Thus, assuming for the sake of argument that a
skilled artisan reading Sterk “could not foresee that a particular dye type and
concentration were critical for visibility and reactivity,” this still would not
render Sterk irrelevant as prior art.
Finally, we note that “[n]on-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).
In this case, the obviousness rejection includes Pathak, and Pathak teaches
that the dye concentration should be selected in an amount sufficient to
provide color while avoiding potential interference with formation of
crosslinked polymer such as fibrin glue. FF19.
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Appellant argues that “Sterk and Pathak are not related or combinable
in the manner urged by the Examiner.” Appeal Br. 6 (formatting omitted).
In particular, while Appellant concedes that Pathak discloses that fibrinogen
or fibrin may be crosslinked using reactive precursor species with
electrophilic functional groups, Appellant contends that the crosslinkers
taught in Pathak are neither thrombin, nor factor XIII, which is disclosed in
Sterk and induces the crosslinking of fibrin. Id. at 6–7; FF4. Appellant
contends that “Pathak could not teach or motivate one to do routine
experimentations with a thrombin solution and visualization agents when
Pathak does not teach thrombin for this purpose.” Id. at 7. Appellant
contends that
[u]sing dye concentrations in the cross-linker precursors taught
in Pathak cannot foresee any problem exerted by visualization
agents on liquid thrombin. Accordingly, there is no motivation
to limit the concentration of a specific dye in a thrombin
solution. Therefore, Pathak cannot motivate the skilled in the
art aware of Sterk to limit the concentration of a specific dye in
a thrombin solution.
Appeal Br. 7.
We are not persuaded. Sterk and Pathak, like the claimed invention,
are both directed to biocompatible crosslinked polymers useful in surgical
procedures. FF4, FF10. The references are also both reasonably pertinent to
at least one of the problems the claimed invention is attempting to solve, i.e.,
visualization of the polymer during surgical procedures. FF1, FF2, FF11–
FF13.6 Accordingly, the references are analogous art for purposes of

6 Appellant argues that Pathak categorizes fibrin sealants as “other” adhesive
sealants and thus “confirms that fibrin sealants are different than sealants
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determining obviousness, and we disagree with Appellant’s assertion that
they are not related.
Neither are we persuaded by Appellant’s argument that a skilled
artisan would not have had reason to use the visualization agent
concentrations taught in Pathak in Sterk’s composition, and to further
optimize such concentration through routine experimentation, simply
because Pathak does not explicitly teach blood coagulation factor XIII, the
catalyst in Sterk’s composition capable of inducing fibrin crosslinking, or
the combination of thrombin with fibrinogen.
As the Supreme Court has explained, in analyzing “whether there was
an apparent reason to combine . . . known elements in the way a patent

disclosed in Pathak.” Appeal Br. 7. We are not persuaded. The paragraphs
in Pathak cited as support by Appellant in fact shows that the Pathak’s
claimed invention is intended to encompass fibrin sealants. See, e.g., Pathak
2:25–38 (disclosing an embodiment of a hydrogel comprising reactive
hydrophilic polymers that form a crosslinked hydrogel after contacting
tissue, wherein the hydrophilic polymers may be fibrinogen); 6:30–33
(disclosing that “[n]atural polymers . . . e.g., collagen, fibrinogen . . . and
fibrin, may be crosslinked using reactive precursor species with electrophilic
functional groups); 25:6–14 (disclosing that “biocompatible crosslinked
polymers and their precursors described above may be used in a variety of
applications,” which are reviewed in a reference entitled “Fibrin Sealant”).
As to Appellant’s argument that Pathak categorizes fibrin sealants as “other”
adhesive sealants, Appeal Br. 7 (citing Pathak 25:18–22), the sentence in
question states: “The various methodologies and devices for performing ‘in
situ’ gelation, developed for other adhesive or sealant systems such [as]
fibrin glue or sealant applications, may be used with the biocompatible
crosslinked polymers of this invention.” Pathak 25:18–22. While this
statement suggests that there may be fibrin glue or sealant applications that
do not fall within the scope of Pathak’s claims, it does not suggest, as
Appellant appears to argue, that the claimed sealants are distinct from and do
not encompass any fibrin sealant.
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claims, it is not necessary to “seek out precise teachings directed to the
specific subject matter of the challenged claim, for a court can take account
of the inferences and creative steps that a person of ordinary skill in the art
would employ.” KSR, 550 U.S. at 418. In this case, Sterk discloses
concentration ranges of visualization agents that were found to “give a color
to the hydrogel that was desirable without interfering with crosslinking.”
FF19. A skilled artisan would have reason to use these visualization agent
concentrations in Sterk’s composition as a starting point and to further
optimize them for the particular ingredients of the composition such that a
desirable color is achieved without interfering with the activities (e.g.,
crosslinking) of other components of the composition. See MPEP
§ 2144.05.II(A) (“Generally, differences in concentration . . . will not
support the patentability of subject matter encompassed by the prior art
unless there is evidence indicating such concentration . . . is critical.”) (citing
cases).
Finally, Appellant contends that the recited concentrations of the
claimed visualization agent in claim 1 produce unexpected results. Appeal
Br. 7–8. Appellant contends that a skilled artisan “could not have
anticipated that [t]he selected dyes and concentrations would have achieved
the desired results of [thrombin] activity and [film] visibility,” because none
of the cited references suggests the effect of visualization agent on thrombin
activity. Id. at 8. Citing the Nur Declaration,7 Appellant contends that “[i]t
was surprisingly found that thrombin activity is affected by dyes” and that
“indigo carmine and methylene blue can be present in a thrombin solution of

7 Rule 132 Declaration of Israel Nur Ph.D. (Dec. 17, 2015).
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a fibrin sealant formulation . . . within a narrow-claimed concentration . . .
without compromising the activity of thrombin or visualization of a fibrin
film on a tissue surface.” Id. at 7–8.
We are not persuaded. As an initial matter, assuming for the sake of
argument that none of the references suggests that the concentration of
visualization agents would affect thrombin activity, Appellant’s observation
of that property does not demonstrate unexpected results we find sufficient
to overcome the evidence of obviousness on this record. As discussed
above, the combination of Sterk and Pathak renders the film of claim 1
prima facie obvious. “Mere recognition of latent properties in the prior art
does not render nonobvious an otherwise known invention.” In re Baxter
Travenol Labs., 952 F.2d 388, 392 (Fed. Cir. 1991). Instead, “any superior
property must be unexpected to be considered evidence of non-
obviousness,” Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1371 (Fed. Cir.
2007) (finding Appellant’s evidence of non-obvousness “must fail because
the record is devoid of any evidence of what the skilled artisan would have
expected”). Appellant has not provided persuasive evidence as to what, if
anything, a skilled artisan would have expected with respect to the potential
interaction between thrombin and visualization agents.
Indeed, in this case Pathak suggests that, depending on their
concentration, visualization agents such as methylene blue can interfere with
crosslinking in the formation of polymer systems. See FF19. Thus, if
anything, the evidence of record suggests that a skilled artisan would have
expected the potential interaction between these agents and other
components in the formation of a crosslinked polymer such as fibrin.
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Neither has the Appellant shown persuasive evidence of other
unexpected results. Dr. Nur first states that it was “surprisingly found that
only blue dyes are suitable for the purpose” of the invention. Nur Decl. 2:3–
6; see also id. at 5:9–6:11.
We are not persuaded. “[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) (quoting In re De Blauwe, 736 F.2d 699, 705
(Fed. Cir. 1984)). In addition,
[t]he 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 [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.’).
In re American Acad. of Science Tech Ctr., 367 F.3d 1359, 1368 (Fed. Cir.
2004) (alterations in original).
In this case, Dr. Nur describes an “experiment [in which] the colors
[of] fibrin sealant mixtures [were] tested for visibility in a laparoscopic
procedure by 6 different assessors.” Nur Decl. 5:13–6:11. However, while
Dr. Nur declares that the blue color was assessed to be “exceptional” and
that “[a]ll participants expressed their genuine astonishment that the blue
dyes that have color shading as blue veins would be the collective choice,”
Nur Decl. 6:5–11, no supporting data was provided that would allow the
Board to evaluate these conclusory statements. For instance, the Nur
Declaration does not provide any details regarding the standards by which
the visualization agents were assessed or whether the differences between
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the different colors were statistically significant. Indeed, it is not even clear
that the “blue color” used in the experiment falls within the claims, as claim
1 recites only methylene blue and indigo carmine. Given the lack of
sufficient supporting details, we find that the declaration does not weigh
heavily or overcome the evidence of obviousness here.
In addition, we note that Pathak teaches that “[t]he preferred color [of
the visualization agent] is green or blue because it has better visibility in
presence of blood or on a pink or white tissue background.” FF18. Thus,
we are further unpersuaded on this record that a skilled artisan would have
found it unexpected that blue dyes such as methylene blue and indigo
carmine are suitable for use (indeed, advantageous) as visualization agents in
a fibrin film to be used on a tissue surface.8
Appellant also argues that the claimed invention exhibits unexpected
results because, according to Dr. Nur, “surprisingly, we found that . . .
utilizing a very narrow [range] dye concentrations can resolve the problem”
of the detrimental effect of methylene blue dye on thrombin when exposed
to light in a liquid mixture. Nur Decl. 2:16–19. Dr. Nur cites to Tables 2
and 3 of the Specification as evidencing that “among various dyes tested,
only methylene blue and indigo carmine at the narrow claimed
concentrations do not compromise the thrombin activity.” Id. at 3:10–15.

8 We acknowledge the statement in the Nur Declaration that a skilled artisan
“will not refer to Pathak . . . or combine Pathak with Sterk since Pathak is
not dealing with biological sealants and/or to thrombin mixtures and thus is
not relevant to dyes or dye concentrations in the pharmaceutical entities of a
biological FS, such as thrombin.” Nur Decl. 6:13–16. However, we are not
persuaded for reasons already discussed above with respect to the
Examiner’s prima facie case of obviousness.
Appeal 2019-003265
Application 12/665,810

18
We are not persuaded. First, the tables in the Nur Declaration and the
Specification do not provide data on indigo carmine, which is also recited in
claim 1. Thus, at the very least, Appellant has not shown unexpected results
commensurate with the scope of the claim. In re Dill, 604 F.2d 1356, 1361
(CCPA 1979) (“The evidence presented to rebut a prima facie case of
obviousness must be commensurate in scope with the claims to which it
pertains.”). Second, based on Dr. Nur’s analysis, the concentrations of
methylene blue tested appears to be limited to 0.05% and 0.1%, which is
outside of the claimed concentration of 0.005% to 0.025%.9 Spec. 22:1–10
(Table 2), 23:16–19 (Table 3); Nur Decl. 3:10–5:5. Thus, Appellant has not
sufficiently demonstrated that there is a “nexus” between its evidence and
the concentration of visualization agents recited in claim 1. In re GPAC
Inc., 57 F.3d 1573, 1580 (Fed. Cir. 1995) (“For objective evidence [of
nonobviousness] to be accorded substantial weight, its proponent must

9 Claim 1 recites the concentration of the visualization agents in a solution
that also comprises fibrin, thrombin, a co-stabilizer, and water. Tables 2 and
3 in the Specification sets forth only the concentration of the dye (i.e.,
visualization agent) in the thrombin component. Thus, it is unclear how one
would convert the dye concentrations in Tables 2 and 3 to a concentration
relevant to claim 1 (i.e., the concentration of the dye in the solution recited
in claim 1). In his Declaration, Dr. Nur appears to assume that the dye
concentration relevant to claim 1 would be the concentration of the dye in a
1:1 fibrinogen:thrombin solution and that this concentration would be half of
the concentration of the dye in the thrombin solution. Nur Decl. 4:1–5:5.
While we are not persuaded of the soundness of Dr. Nur’s assumptions, we
make the same assumptions in our discussion of Appellant’s unexpected
results argument, because even under these assumptions Appellant’s
proffered factual evidence is unpersuasive.
Appeal 2019-003265
Application 12/665,810

19
establish a nexus between the evidence and the merits of the claimed
invention.”).
CONCLUSION
In summary:

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

Claims
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
1, 4, 16, 64,
69, 72, 73,
75–81
103(a) Sterk, Pathak, the
Material Safety
Data Sheet
(MSDS) for
methylene blue,
Tse
1, 4, 16, 64,
69, 72, 73,
75–81