ACell, Inc.

Patent Trials and Appeals Board

Sep 29, 2020

2020001646 (P.T.A.B. Sep. 29, 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.
14/860,781 09/22/2015 Chandra M. Valmikinathan SPV-016 8621
26486 7590 09/29/2020
BURNS & LEVINSON, LLP
125 HIGH STREET
BOSTON, MA 02110
EXAMINER
PARK, HAEJIN S
ART UNIT PAPER NUMBER
1615
NOTIFICATION DATE DELIVERY MODE
09/29/2020 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):
docketing@burnslev.com
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte CHANDRA M. VALMIKINATHAN,
NIKHIL NIRAJ GHEEWALA, BRENT DONALD YOUNG, and
THOMAS WAYNE GILBERT1
____________

Appeal 2020-001646
Application 14/860,781
Technology Center 1600
____________

Before JEFFREY N. FREDMAN, DEBORAH KATZ, and
JOHN G. NEW, Administrative Patent Judges.

NEW, Administrative Patent Judge.

DECISION ON APPEAL

1 We use the word “Appellant” to refer to “applicant” as defined in 37
C.F.R. § 1.42. Appellant identifies ACell, Inc. as the real party-in-interest.
App. Br. 3.

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SUMMARY
Appellant files this appeal under 35 U.S.C. § 134(a) from the
Examiner’s Final Rejection of claims 1, 4–8, 10, and 17–20. Specifically,
claims 1, 4–8, 10, and 17–20 stand rejected as unpatentable under 35 U.S.C.
§ 103 as being obvious over the combination of Badylak et al. (US
2008/0260831 A1, October 23, 2008) (“Badylak”), Patel et al. (US
2014/0271472 A1, September 18, 2014) (“Patel”), and Malaviya et al. (US
8,025,896 B2, September 27, 2011) (“Malaviya”).
The Examiner also rejected claim 17 under 35 U.S.C. § 112(b) as
being indefinite.
We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.

NATURE OF THE CLAIMED INVENTION
Appellant’s claimed invention is directed to a method for making a
medical foam device from an extracellular matrix (“ECM”) material. Abstr.

REPRESENTATIVE CLAIM
Claim 1 is representative of the claims on appeal and recites:
1. A method for making a medical foam device, comprising:
(a) solubilizing dehydrated extracellular matrix material
obtained from a mammalian tissue in a solution with a pH less
than 4.0 or a pH greater than 9.0 in the absence of an enzyme;
(b) blending said acidified (pH<4) or basic (pH>9)
solubilized extracellular matrix material in an industrial blender
at speeds in the range of about 500 RPM to about 2500 RPM to
form a foamy extracellular matrix material slurry;
(c) adding one or more minerals during step (b)
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(d) mixing said foamy extracellular matrix material slurry
in a buffering solution to neutralize said foamy extracellular
matrix material slurry with added minerals to a pH of about 7;
(e) introducing said neutralized foamy extracellular matrix
material slurry of step (d) into a mold;
(f) lyophilizing said neutralized molded foamy
extracellular matrix material slurry in pre-cooled lyophilizer
shelves; followed by;
(g) introducing ice crystals into said lyophilized molded
extracellular matrix material of step (f) at a temperature range
between 0°C to -40°C for periods of time ranging between 0
minutes to 240 minutes; and,
(h) sublimating said ice crystals introduced in step (g) at a
vacuum pressure in the range of 60–120mmHg to produce said
medical foam device.
App. Br. 17–18.

ISSUES AND ANALYSIS
We agree with, and expressly adopt, the Examiner’s findings,
reasoning, and conclusion that the claims are obvious and indefinite (with
respect to claim 17). We address below the arguments raised by Appellant.

A. Rejection of the claims over Badylak, Patel, and Malaviya
Issue 1
Appellant argues that the Examiner erred in finding that the combined
prior art teaches the claimed method in the claimed order of steps to make a
medical foam device. See App. Br. 9–10, 15.

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Analysis
The Examiner finds that Badylak teaches a method of preparing an
ECM-derived gel including the steps of: (1) solubilizing dehydrated
mammalian ECM by digesting with an enzyme in an acidic solution having
a pH between 2 and 4; (2) blending the acidified ECM mixture; (3)
neutralizing the ECM mixture with a buffer to form a pre-gel; (4) placing the
pre-gel in a suitable mold; and (5) gelling the mixture. Final Act. 4–5. The
Examiner acknowledges that Badylak does not teach: (1) solubilizing ECM
in the absence of an enzyme (in claimed step (a)); (2) adding one or more
minerals (claimed step (c)); and (3) the lyophilizing process (claimed steps
(f)–(h)). Id. at 6.
The Examiner finds that Patel teaches a method of preparing an ECM-
derived foam including the steps of: (1) solubilizing dehydrated mammalian
ECM by digesting in an acidic solution; (2) foaming the ECM gel mixture
with mechanical techniques, e.g., aerating; (3) neutralizing the acidic ECM
mixture; (4) casting the foamed ECM material into a mold; and (5)
lyophilizing the foamed ECM gel material to form a porous medical device.
Final Act. 6–8. The Examiner finds that Patel teaches solubilizing ECM in
an acid in the absence of an enzyme, resulting in a neutralized non-toxic
material that is free of digestive enzyme. Id. at 6. The Examiner finds that
Patel teaches adding bioactive agents to the mixture before forming the gel.
Id. at 8.
The Examiner finds that Malaviya teaches a method of preparing
ECM foams by: (1) preparing a slurry of ECM material; (2) placing the
slurry in a container; and (3) lyophilizing the slurry. Final Act. 8–9. The
Examiner finds that Malaviya teaches adding biocompatible inorganic
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materials including calcium or phosphate salts to the ECM material at the
time of manufacture, prior to forming the ECM foam. Id. at 9. The
Examiner further finds that Malaviya teaches detailed parameters for
lyophilizing, including: (1) pre-freezing a container to -20°C; (2)
lyophilizing ECM material at a temperature of -13°C for 8 hours; and (3)
sublimating ice crystals under vacuum and low temperatures. Id. at 8–9.
The Examiner therefore concludes that it would have been obvious to
a person of ordinary skill in the art to prepare an ECM foam by digesting
ECM in an acid in the absence of a digestive enzyme, foaming the ECM
mixture in a blender, adding a mineral, neutralizing the mixture, adding the
mixture to a mold, and lyophilizing the mixture under the claimed
conditions. Final Act. 9. The Examiner arrives at this conclusion because
all the references teach methods for preparing ECM-derived medical devices
including the claimed steps limited by result-effective parameters, e.g.,
digesting in acid, blending, and lyophilizing. Id. at 9–10.
Appellant argues that Badylak’s method is “fundamentally different”
from the claimed method because Badylak “is entirely about methods of
making gels.” App. Br. 6 (emphasis in original). Appellant argues that
Badylak’s blending step does not form a foamy ECM material slurry, and
Badylak’s method does not end with lyophilizing the mixture to form a
foam. Id. at 8. Likewise, Appellant argues that Patel teaches forming a gel
by alkaline treatment at elevated temperature, as opposed to blending
solubilized ECM material at speeds sufficient to form a foamy ECM slurry.
Id. at 11. Appellant argues that the Examiner “randomly” chooses from
“different sections of Patel referring to various forms of ECM materials,
including particulate, expanded, gel, dried and foam shapes.” Id. Appellant
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further argues that neither Badylak, Patel, nor Malaviya teach the order of
steps in the claimed method because the references fail to disclose all of the
ordered steps. Id. at 9–10, 15.
We are not persuaded by Appellant’s argument. We begin with
Appellant’s arguments against the references individually rather than the
combination. “Non-obviousness cannot be established by attacking
references individually where the rejection is based upon the teachings of a
combination of references.” In re Merck & Co., 800 F.2d 1091, 1097 (Fed.
Cir. 1986). Patel teaches that ECM gels, such as those taught by Badylak,
can be expanded into foamed forms, e.g., foamy slurries, by mechanical
techniques, e.g., aeration, alkaline treatment, or heat treatment. Patel ¶¶ 39,
42, 47, 71. Patel expressly teaches that acid digestion is an alternative to
enzyme digestion, resulting in a non-toxic preparation free of digestive
enzyme. Id. ¶ 31. Patel further teaches adding bioadditives before, during,
or after forming the gel, casting the foamed gel into a mold, and lyophilizing
material to form a foamed device. Id. ¶¶ 37, 71. Although the Examiner
picks and chooses from Patel’s different teachings, such picking and
choosing is entirely proper in the making of a § 103, obviousness rejection.
In re Arkley, 455 F.2d 586, 587 (C.C.P.A. 1972).
With respect to the claimed order of steps, we agree with the
Examiner that the claimed order, including the step of adding minerals to the
mixture after blending but before neutralizing the mixture, would have been
obvious to a person of ordinary skill in the art. See Final Act. 9. Patel
teaches that the bioactive materials may be added throughout the gel-
forming process. Patel ¶ 37. Specifically, Patel teaches “incorporating the
additional component(s) into an aqueous, ungelled composition of the ECM
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hydrolysate before, during (e.g. with) or after addition of the neutralization
agent.” Id. Similarly, Malaviya teaches incorporating biocompatible
inorganic materials, e.g., minerals, “prior to the formation of the ECM
foam.” Malaviya col. 12, ll. 14–16. We therefore find that the prior art
collectively suggests “doing the thing that appellant has done in this case”
and conclude that the claims would have been obvious absent evidence of
new or unexpected results due to the claimed order of steps. See In re
Burhans, 154 F.2d 690, 692 (C.C.P.A. 1946). Appellant provides no
evidence that the order of steps, particularly the sequence of “(c) adding one
or more mineral during step (b),” provides new or unexpected results over
the prior art that teaches the addition of the mineral, but does not specify at
which step the addition occurs.

Issue 2
Appellant argues that a person of ordinary skill in the art would not
have been motivated to combine the references because the combination
would render Badylak inoperable for its intended use. See App. Br. 12–14.

Analysis
Appellant argues that “adding the steps of aerating and lyophilizing
to the method of making the gel of Badylak are inappropriate modifications
for an obviousness inquiry because the modifications render the gel of
Badylak inoperable for its intended purpose.” App. Br. 12. Specifically,
Appellant argues that modifying Badylak’s gel by aerating and lyophilizing
according to Patel would change Badylak’s flowable gel into a porous solid
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structure. Id. at 13. Appellant contends that the change would frustrate
Badylak’s intended purpose of using a gel to infiltrate a porous scaffold
thereby permitting tissue in-growth. Id. at 14.
We are not persuaded by Appellant’s argument. Badylak, Patel, and
Malaviya concern reactions for processing ECM materials to form medical
devices. See supra. The references further recognize that the reaction
conditions can be varied to produce different final products. See Patel ¶¶ 39,
43, 47. Although Badylak teaches the benefits of gel formulations, Patel and
Malaviya teach the desirable properties of ECM-derived foams. For
example, Patel teaches that “[t]he more foamy and porous structure of an
expanded ECM … can allow the material to be cast or otherwise prepared
into a variety of sponge or foam shapes for use in the preparation of medical
materials and devices.” Id. ¶ 47. Malaviya teaches that “ECM foams …
provide a relatively large surface area of naturally occurring ECM … [that]
can be advantageous in providing a relatively large surface area to which …
biocompatible inorganic materials can be affixed pre-implantation.”
Malaviya 11:42–49. Appellant adduces no evidence, nor can we discern
any, to support the premise that the cited prior art teaches or suggests that
the proposed modification of converting a gel to a foam would result in an
inoperable process, or a foam with undesirable properties. Accordingly, a
person of ordinary skill in the art would have been motivated to pursue the
desirable properties of ECM foams taught by Patel and Malaviya, even at the
expense of the benefits of ECM gels taught by Badylak. See In re Urbanski,
809 F.3d 1237, 1243 (Fed. Cir. 2016).

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Issue 3
Appellant argues that the Examiner erred in finding that the combined
prior art teaches blending in an industrial blend at speeds in the range of 500
RPM to about 2500 RPM to form a foamy ECM material slurry. See App.
Br. 8–9.

Analysis
Appellant argues that “Badylak’s blending is an action associated with
solubilizing for a period of 12–48 hours.” App. Br. 8. Appellant contrasts
the claimed step (b) which “is performed ‘at speeds in the range of about
500 RPM to about 2500 RPM to form a foamy extracellular matrix material
slurry.’” Id. Appellant further argues that Patel requires neutralizing an
ECM hydrolysate prior to aerating to form a foam, and thus “Patel at least
does not teach or suggest blending solubilized ECM material at speeds
sufficient to form a foamy ECM material slurry as recited in step (b).” Id. at
11.
The Examiner responds that Badylak teaches solubilizing ECM by
blending and Patel teaches foaming ECM material by mechanically aerating.
Ans. 6. The Examiner finds that “[o]ne having ordinary skill in the art at the
time of filing would have recognized that the foamed ECM gel material
would form a slurry comprising bubbles and particulate ECM material.” Id.
With respect to the blending speed, the Examiner finds that Appellant has
not established that the claimed range is critical by showing that the claimed
speed provides unexpected results over the prior art. Id.
We are not persuaded by Appellant’s arguments. The combination of
Badylak and Patel teaches that blending an ECM digestion mixture may
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result in a foamy mixture. See Patel ¶ 39. Accordingly, the blending speed
is a result-effective variable that can be varied to adjust the ECM foam’s
properties in a predictable manner. See Urbanski, 809 F.3d at 1242. Our
reviewing court has explained that:
The law is replete with cases in which the difference between the
claimed invention and the prior art is some range or other
variable within the claims. These cases have consistently held
that in such a situation, the applicant must show that the
particular range is critical, generally by showing that the claimed
range achieves unexpected results relative to the prior art range.
In re Woodruff, 919 F. 2d 1575, 1578, 16 USPQ2d 1934, 1936 (Fed. Cir.
1990). Appellant has not submitted any evidence showing that the claimed
range achieves unexpected results relative to the prior art. Accordingly, we
are not persuaded that the Examiner erred.
We consequently affirm the Examiner’s rejection of the claims.

B. Rejection of claim 17 as indefinite
The Examiner finds that claim 17 recites a broad limitation together
with a narrow limitation that falls within the broad limitation. Final Act. 3.
Specifically, the Examiner finds claims 17 recites a genus, viz., “calcium and
phosphate salts,” and species within the genus, viz., “calcium nitrate and
tricalcium phosphate.” Id. A claim that recites both a broad limitation and a
narrow limitation within the broad limitation is indefinite under 35 U.S.C.
§ 112(b) because the boundaries of the claim are not discernible. See MPEP
§ 2173.05(c).
Appellant does not address the indefiniteness rejection in the Appeal
Brief. See generally App. Br. We consequently summarily affirm this
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rejection. See 37 C.F.R. § 41.37(c)(iv) (“[A]ny arguments or authorities not
included in the appeal brief will be refused consideration by the Board for
purposes of the present appeal”).

CONCLUSION
The Examiner’s rejection of claims 1, 4–8, 10, and 17–20 as
unpatentable under 35 U.S.C. § 103 is affirmed.
The Examiner’s rejection of claim 17 as unpatentable under 35 U.S.C.
§ 112(b) is affirmed.
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

Claims
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
1, 4–8, 10,
17–20
103 Badylak, Patel, Malaviya 1, 4–8, 10,
17–20

17 112(b) Indefiniteness 17
Overall
Outcome
1, 4–8, 10,
17–20