Sengun, Mehmet Z. et al.

Patent Trials and Appeals Board

Apr 21, 2020

13250086 - (D) (P.T.A.B. Apr. 21, 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.
13/250,086 09/30/2011 Mehmet Z. Sengun 47062-032F01US 9894
30623 7590 04/21/2020
Mintz Levin/Boston Office
One Financial Center
Boston, MA 02111
EXAMINER
CLARKE, TRENT R
ART UNIT PAPER NUMBER
1651
NOTIFICATION DATE DELIVERY MODE
04/21/2020 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):
IPDocketingBOS@mintz.com
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PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte MEHMET Z. SENGUN,
WILLIAM PARRISH, GREGORY R. WHITTAKER,
DOUGLAS A. FIFOLT, and BROOKS J. STORY
Appeal 2019-003273
Application 13/250,086
Technology Center 1600
Before DONALD E. ADAMS, ERIC B. GRIMES, and TAWEN CHANG,
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, 5–10, 13, 17–20, and 53. 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 the real party in interest as DePuy Mitek,
LLC. Appeal Br. 1.
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BACKGROUND
According to the Specification, “[u]pon injury to the skin, a set of
complex biochemical events takes place in a closely orchestrated cascade to
repair the damage. Within minutes post-injury, platelets (thrombocytes)
aggregate at the injury site to form a fibrin clot. This clot acts to control
active hemostasis.” Spec. ¶ 3.
Further according to the Specification,
[i]t has been discovered that dimensionally stable, fibrin constructs
can be reproducibly obtained from clotted blood and can substantially
promote wound healing. For example, fibrin constructs are useful for
local administration to a wound site or region. The fibrin constructs
can also include components that promote wound healing, such as
platelets, growth factors, white blood cells, aggregated fibrin and
growth factors and/or other proteins.
Spec. ¶ 70.
CLAIMED SUBJECT MATTER
The claims are directed to a method of reproducibly preparing a
growth factor enriched fibrin construct. Claim 1, the only independent
claim, is illustrative:
1. A method of reproducibly preparing a growth factor
enriched fibrin construct, comprising:
(a) collecting a human blood sample comprising
unaggregated fibrin, wherein collecting the blood sample
comprises exposing the blood sample to an anti-coagulant;
(b) mixing the blood sample in a borosilicate glass
container with a coagulation activator consisting of a calcium
salt to initiate aggregation of the fibrin;
(c) exposing the blood mixture to a separation force,
thereby producing a dimensionally stable, suturable growth
factor enriched fibrin construct comprising a fibrin layer, a
platelet layer and a red blood cell layer, wherein said separation
force is a single centrifugation with a speed of about 2000g to
about 3,000g;
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wherein the fibrin construct has a growth factor enriched
surface concentrated with blood cells and platelets and an
opposed, growth factor depleted surface; wherein the growth
factor enriched surface is capable of releasing a growth factor
and wherein the released growth factor comprises at least about
5ng of vascular endothelial growth factor (VEGF) within 24
hours.
Appeal Br. App. A: Claims on Appeal, A.
REJECTION(S)2
A. Claims 1, 5–10, 13, 20, and 53 are rejected under pre-AIA 35 U.S.C.
§ 103(a) as being unpatentable over Harrison,3 Hood,4 Sorvall,5
Thermo Scientific,6 and Ariëns.7
B. Claims 1, 5–10, 13, 17–20, and 53 are rejected under pre-AIA 35
U.S.C. § 103(a) as being unpatentable over Harrison, Hood,
Ehrenfest,8 Beretta,9 Sorvall, Thermo Scientific, and Ariëns.

2 In the Answer, the Examiner withdrew both of the rejections originally on
appeal and issued the two new grounds of rejection discussed herein. Ans.
3, 12.
3 Sophia Harrison et al., Platelet Activation by Collagen Provides Sustained
Release of Anabolic Cytokines, 39 AM. J. SPORTS MED. 729 (2011).
4 Hood, III, US 5,733,545, issued Mar. 31, 1998.
5 Kendro Laboratory Products, Sorvall® RC-3C Plus and RC-3B Plus
(2000).
6 Thermo Fisher Scientific Inc., Large Capacity Rotors: Thermo Scientific
H-12000 Blood Processing Rotor (2010).
7 Robert A.S. Ariëns et al., Role of Factor XIII in Fibrin Clot Formation and
Effects of Genetic Polymorphisms, 100 BLOOD 743 (2002).
8 David M. Dohan Ehrenfest et al., Review, Classification of Platelet
Concentrates: from Pure Platelet-rich Plasma (P-PRP) to Leucocyte- and
Platelet-rich Fibrin (L-PRF), 27 TRENDS IN BIOTECHNOLOGY 158 (2008).
9 Beretta et al., US 7,745,106 B2, issued June 29, 2010.
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OPINION
A. Issue
The Examiner rejects claims 1, 5–10, 13, 20, and 53 as obvious over
Harrison, Hood, Sorvall, Thermo Scientific, and Ariëns. The Examiner also
rejects claims 1, 5–10, 13, 17–20, and 53 as obvious over Harrison, Hood,
Ehrenfest, Beretta, Sorvall, Thermo Scientific, and Ariëns. The same issues
are dispositive for both rejections; we therefore discuss them together.
The Examiner finds that Harrison suggests almost all of the
limitations of claim 1, except that it (1) does not explicitly “specify the
centrifugal force provided by their centrifugation step;” (2) does not
explicitly teach “a dimensionally stable, suturable growth factor enriched
fibrin construct comprising a fibrin layer, a platelet layer and a red blood cell
layer,” wherein “the fibrin construct has a growth factor enriched surface
concentrated with blood cells and platelets and an opposed, growth factor
depleted surface” and wherein “the growth factor enriched surface is capable
of releasing a growth factor and . . . the released growth factor comprises at
least about 5ng of vascular endothelial growth factor (VEGF) within 24
hours”; and (3) “teaches using bovine thrombin with 10% calcium chloride,
and doesn’t teach using calcium chloride as the sole coagulation activator
(i.e. a coagulation activator consisting of a calcium salt).” Ans. 5–8
(emphasis added).
With respect to the limitation relating to centrifugal force, the
Examiner finds that Harrison teaches centrifuging the blood mixture at 2500
rpm in the supernatant extraction step. Ans. 5. The Examiner finds that
Harrison uses a Sorvall RC3 centrifuge from Thermo Scientific, which has
an “effective radius (r) [of rotation] of 26.26 cm,” which in turn “would
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apply a centrifugal force of ~ 1820 x g.” Id. The Examiner further finds
that “Harrison is studying how the parameters of clot formation, e.g. platelet
concentration and . . . activators, affect the kinetics of growth factor release
from the fibrin constructs (clots),” and that a skilled artisan
would have found it obvious that centrifugal force used in
formation of the fibrin constructs would affect the structure of
the fibrin constructs (e.g. greater centrifugal force would
produce a more compressed construct) which would affect
growth factor release, i.e. centrifugal force is a result effective
variable affecting growth factor release from the constructs;
hence, the ordinarily skilled artisan would find it obvious to
adjust the centrifugal force to optimize the constructs produced
and arrive at the claimed invention.
Id. at 5–6.
With respect to the limitation relating to the amount of VEGF being
released within 24 hours by the growth factor enriched surface of the fibrin
construct, the Examiner finds that Harrison teaches measuring the amount of
VEGF released into 5 ml of blood at 7 different time points and that “the clot
from each time point . . . releases about 0.2 ng VEGF/ml,” or 1 ng of VEGF
released from each of 7 time points. Ans. 6. The Examiner finds that,
accordingly, “a . . . clot not distributed over a time course would be capable
of releasing at least 7 ng VEGF in 24 h.” Id.
The Examiner also finds, with respect to this limitation and the
limitations relating to certain other structural and functional characteristics
of the claimed fibrin construct (i.e., “dimensionally stable,” “suturable,”
“growth factor enriched,” “comprising a fibrin layer, a platelet layer and a
red blood cell layer,” having “a growth factor enriched surface concentrated
with blood cells and platelets” capable of releasing a growth factor and “an
opposed, growth factor depleted surface”) to be inherently disclosed,
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because “the method made obvious by Harrison for producing a therapeutic
clot meets all of the positively recited steps of the claimed method.” Ans. 8.
Finally, with respect to the limitation regarding “a coagulation
activator consisting of a calcium salt,” the Examiner finds that
Hood teaches that calcium chloride alone is sufficient . . . for
clot formation from human anticoagulated (ACD) plasma-buffy
coat concentrate (which comprises white blood cells and
platelets and has had red blood cells removed . . .), teaches that
no thrombin was added . . . , teaches that the calcium chloride
neutralizes the free citrate from the ACD . . . and that the
calcium ions alone are sufficient for clot formation.
Id. at 7. The Examiner further finds that “Hood teaches ‘[a]n advantage of
use of calcium over other techniques for initiating clotting is the absence of
need for exogenous thrombin, the source of some number of patient
complications.’” Id. (brackets added).
The Examiner concludes that, given Hood’s teachings, a skilled
artisan would have found it obvious to use “calcium chloride as the sole
coagulation activator to initiate aggregation of the fibrin (i.e. wherein the
coagulation activator consists of a calcium salt),” in place of the bovine
thrombin and calcium chloride taught in Harrison. Ans. 7.
Appellant contends among other things that the cited combination of
reference do not “disclose or suggest the claimed method of reproducibly
preparing a growth factor enriched fibrin construct” that includes at least the
step of “exposing the blood mixture to a separation force, thereby producing
a dimensionally stable, suturable growth factor enriched fibrin construct
comprising a fibrin layer, a platelet layer and a red blood cell layer,” wherein
the fibrin construct has the characteristics recited in the claims. Reply Br. 3.
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B. Analysis
We agree with Appellant that the Examiner has not established a
prima facie case that the claims are obvious over the cited prior art.
The claims require “exposing the . . . mixture [of a human blood
sample and a coagulation activator consisting of a calcium salt] to a
separation force, thereby producing a dimensionally stable, suturable growth
factor enriched fibrin construct comprising a fibrin layer, a platelet layer and
a red blood cell layer, wherein the separation force is a single centrifugation
with a speed of about 2000g to about 3,000g.” Appeal Br. App. A: Claims
on Appeal, A. The Examiner asserts that the cited prior art combination
teaches this limitation because Harrison teaches preparing whole blood and
platelet-rich plasma (PRP) samples containing bovine thrombin reconstituted
with 10% calcium chloride, allowing the samples to clot, and then extracting
“supernatant exuded from [the] clot” by centrifuging the sample at 2500 rpm
for 10 minutes. Ans. 5. Based on Harrison’s disclosure that a Sorvall RC3
centrifuge from Thermo Scientific was used to extract the supernatant, the
Examiner calculates that the centrifuge would apply 1820g of centrifugal
force at 2500 rpm.
The Examiner does not assert that 1820g meets the limitation of
“about 2000g to about 3,000g.” However, the Examiner finds that
centrifugal force is a known result effective variable affecting growth factor
release from the constructs and that, therefore, “the ordinarily skilled artisan
would find it obvious to adjust the centrifugal force to optimize the
constructs produced and arrive at the claimed invention.” Ans. 6.
We are not persuaded. While “it is not inventive to discover the
optimum or workable ranges by routine experimentation” where “the general
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conditions of a claim are disclosed in the prior art,” In re Aller, 220 F.2d
454, 456 (CCPA 1955), the centrifugation in Harrison cited by the Examiner
is not used to form a fibrin construct, as recited in the claims, but rather to
extract the supernatant exuded from already formed clots. Harrison 3
(supernatant collected at 2 hours and 1, 2, 3, 4, 5, and 6 days after blood
sample preparation). Indeed, Harrison explains that, after the supernatant
was removed by centrifugation, the tubes containing the clots (i.e., the fibrin
construct) were discarded. Id. Thus, the Examiner has not persuasively
shown that a skilled artisan would have had reason to adjust the
centrifugation speed for purposes of optimizing fibrin constructs rather than
to optimize supernatant extraction.
For the reasons discussed above, we reverse the Examiner’s rejection
of claim 1 as obvious over Harrison, Hood, Sorvall, Thermo Scientific, and
Ariëns. Similarly, the Examiner cites Beretta and Ehrenfest only for the
additional limitations in dependent claims 17–19 relating to, respectively,
blotting, folding, and layering a second fibrin construct on top of the fibrin
construct. Ans. 24–25. Accordingly, we reverse the Examiner’s rejection of
claim 1 as obvious over Harrison, Hood, Ehrenfest, Beretta, Sorvall, Thermo
Scientific, and Ariëns for the same reasons already discussed. We likewise
reverse the rejection of claims 5–10, 13, 17–20, and 53, all of which depend
from claim 1. In re Fine, 837 F.2d 1071, 1076 (Fed. Cir. 1988) (“Dependent
claims are nonobvious under section 103 if the independent claims from
which they depend are nonobvious.”).

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CONCLUSION
In summary:
Claims
Rejected
35 U.S.C.
§
Reference(s)/Basis Affirmed Reversed
1, 5–10, 13,
20, 53
103(a) Harrison, Hood,
Sorvall, Thermo
Scientific, Ariëns

1, 5–10, 13,
20, 53
1, 5–10, 13,
17–20, 53
103(a)

Harrison, Hood,
Ehrenfest, Beretta,
Sorvall, Thermo
Scientific, Ariëns

1, 5–10, 13,
17–20, 53
Overall
Outcome

1, 5–10, 13,
17–20, 53

REVERSED