Tissue Transplant Technology Ltd. & Human Biologics of Texas, Ltd.,v.MiMedx Group, Inc.

Patent Trial and Appeal Board

Jun 29, 2015

13954974 (P.T.A.B. Jun. 29, 2015)

Trials@uspto.gov Paper No. 13
571.272.7822 Entered: June 29, 2015

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

TISSUE TRANSPLANT TECHNOLOGY LTD. &
HUMAN BIOLOGICS OF TEXAS, LTD.,
Petitioner,

v.

MIMEDX GROUP, INC.,
Patent Owner.
____________

Case IPR2015-00320
Patent 8,709,494 B2
____________

Before LORA M. GREEN, SUSAN L. C. MITCHELL, and
CHRISTOPHER G. PAULRAJ, Administrative Patent Judges.

GREEN, Administrative Patent Judge.

DECISION
Denying Institution of Inter Partes Review
37 C.F.R. § 42.108

INTRODUCTION I.
Tissue Transplant Technology LTD (d/b/a Bone Bank Allografts) and
Human Biologics of Texas, Ltd. (collectively, “Petitioner”) filed a corrected
Petition requesting an inter partes review of claims 1–10 of U.S. Patent No.
8,709,494 B2 (Ex. 1001, “the ’494 patent”). Paper 7 (“Pet.”). MiMedx
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Group, Inc. (“Patent Owner”) filed a Preliminary Response to the Petition.
Paper 11 (“Prelim. Resp.”).
We have jurisdiction under 35 U.S.C. § 314, which provides that an
inter partes review may not be instituted “unless . . . there is a reasonable
likelihood that the petitioner would prevail with respect to at least 1 of the
claims challenged in the petition.” 35 U.S.C. § 314(a). Upon considering
the Petition and the Preliminary Response, we determine that Petitioner has
not shown a reasonable likelihood that it would prevail in showing the
unpatentability of claims 1–10. Accordingly, we decline to institute an inter
partes review of those claims.
A. Related Proceedings
Petitioner states that the ’494 patent is the subject of the copending
district court case, MiMedx Group, Inc. v. Tissue Transplant Technology
Ltd. et al., Case No. 1:14-CV-719-HLH (W. D. Tex.). Pet. 1; Paper 9.
Petitioner also filed the following petitions again Patent Owner in the
following requests for inter partes review: IPR2015-00420 (U.S. Patent No.
8,597,687 B2); IPR2015-00664 (U.S. Patent No. 8,372,437 B2); and
IPR2015-00669 (U.S. Patent No. 8,323,701 B1).
B. The ’494 Patent (Ex. 1001)
The ’494 patent issued on April 29, 2014, with John Daniel listed as
the sole inventor. Ex. 1001. The ’494 patent relates to tissue allografts, and
more particularly “to placental membrane tissue grafts (amnion and chorion)
and methods of preparing, preserving, and medical uses for the same.” Id. at
1:20–22.
As taught by the ’494 patent:
The placenta has two primary layers of tissue including
amniotic membrane and chorion. The amniotic membrane is a
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non-vascular tissue that is the innermost layer of the placenta,
and consists of a single layer, which is attached to a basement
membrane. Histological evaluation indicates that the
membrane layers of the amniotic membrane consist of
epithelium cells, thin reticular fibers (basement membrane), a
thick compact layer, and fibroblast layer. The fibrous layer of
amnion (i.e., the basement membrane) contains cell anchoring
collagen types IV, V, and VII. The chorion is also considered
as part of the fetal membrane; however, the amniotic layer and
chorion layer are separate and separable entities.
Id. at 1:36–48. Placental membrane has been used for various types of
reconstructive surgery since the early 1900s, and has also been widely used
in ophthalmic procedures. Id. at 1:26–32.
According to the ’494 patent, in order to prepare the implant,
placental tissue is collected from a hospital. Id. at 5:7–8. The placenta is
removed from the sterile shipment bag and transferred to a sterile processing
basin preferably containing hyperisotonic saline (18% NaCl) solution at
close to room temperature. Id. at 6:12–16. The placenta is gently massaged
to help separate blood clots, allowed to reach room temperature to ease the
separation of the amnion from the chorion, and then placed on a processing
tray with the amniotic membrane layer facing down. Id. at 6:16–24.
With the tissues in the processing tray, the chorion layer is lifted
gently off the amniotic membrane layer, and blood clots are removed from
the layers using a blunt instrument, a finger, or a sterile, non-particulating
gauze. Id. at 6:41–64. The tissue is chemically decontaminated, and then
dehydrated on a drying fixture. Id. at 7:11–8:18. The drying fixture may
have grooves, which may be arranged in a grid, and may also have a design
in the empty spaces of the grid, such as a logo or name. Id. at 8:13–31.
According to the ’494 patent, “[p]referably, such texture/label can be read or
viewed on the tissue in only one orientation so that, after drying and cutting,
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an end user (typically a surgeon) of the dried tissue will be able to tell the
stromal side from the basement side of the dried tissue.” Id. at 8:37–41.
The drying fixture is placed in a dehydration bag, sealed, and placed in a
frying oven at 35 to 50 degrees Celsius for 30 to 120 minutes. Id. at 8:58–
9:15. The ideal drying conditions, however, appear to be at 45 degrees
Celsius for 45 minutes. Id. at 9:5–8. Once the tissue is dehydrated, it can be
cut into specific product sizes, and each cut allograft is placed into its own
pouch. Id. at 9:22–23; 9:45–46.
C. Illustrative Claim
Petitioner challenges claims 1–10 of the ’494 patent, of which claims
1, 6, 9, and 10 are independent. Claim 1, 9, and 10 are illustrative and are
reproduced below.
1. A dehydrated, laminated tissue graft consisting essentially of
one or more washed and/or substantially cleaned amnion layers
and one or more washed and/or substantially cleaned chorion
layers, wherein at least one of the amnion layers contains its
fibroblast cell layer, and further wherein the amnion layer and
the chorion layer are directly laminated to each other.
9. A dehydrated, laminated, placental tissue graft which is a
laminate comprising two or more separated and washed layers
which layers are selected from amnion and/or chorion wherein
the layers are directly laminated to each other and at least one
of said layers is an amnion layer which retains an epithelial cell
layer.
10. A dehydrated, laminated, placental tissue graft which is a
laminate comprising two or more separated and washed layers
which layers are selected from amnion and/or chorion wherein
the layers are directly laminated to each other and at least one
of said layers is an amnion layer which retains a fibroblast
cellular layer.

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D. The Asserted Grounds of Unpatentability
Petitioner challenges the patentability of claims 1–10 of the
’494 patent on the following grounds:
References Basis Claims Challenged
Vishwakarma1 § 102(b)/103(a) 9 and 10
Gray2 § 103(a) 1–10
Gray and Vishwakarma § 103(a) 1–10
Tseng3 and Miljudin4 § 103(a) 9 and 10
Hariri5 and Vishwakarma § 103(a) 1–10
Gray and Miljudin or Tseng § 103(a) 3, 9, and 10

ANALYSIS II.
A. Claim Construction
In an inter partes review, claim terms in an unexpired patent are
interpreted according to their broadest reasonable constructions in light of
the specification of the patent in which they appear. See 37 C.F.R.
§42.100(b); In re Cuozzo Speed Techs., LLC, 778 F.3d 1271, 1280 (Fed. Cir.

1 G. K. Vishwakarma and A. K. Khare (“Vishwakarma”), Amniotic
Arthroplasty for Tuberculosis of the Hip, 68 J. BONE AND JOINT SURGERY
68–74 (1986) (Ex. 1005).
2 Saleh M. Shenaq and Kathy Jo Gray (“Gray”), Pub. No. WO 93/10722,
published Jun. 10, 1993 (Ex. 1006).
3 Tseng, US Patent No. 6,152,142, issued Nov. 28, 2000 (Ex. 1008).
4 Miljudin et al. (“Miljudin”), Silica Gel Dissication of Amniotic Membrane
with Related Epithelium Cells for Ocular Surface Reconstruction, 5 CELL
AND TISSUE BANKING 271–75 (2004) (Ex. 1007).
5 Hariri et al. (“Hariri”), Pub. No. US 2004/0048796 A1, published Mar. 11,
2004 (Ex. 1009).
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2015). Under the broadest reasonable construction standard, claim terms are
presumed to be given their ordinary and customary meaning, as would be
understood by one of ordinary skill in the art in the context of the entire
disclosure. In re Translogic Tech., Inc., 504 F.3d 1249, 1257 (Fed. Cir.
2007). An inventor may rebut that presumption by providing a definition of
the term in the specification with reasonable clarity, deliberateness, and
precision. In re Paulsen, 30 F.3d 1475, 1480 (Fed. Cir. 1994). Under that
standard, and absent any special definitions, we give claim terms their
ordinary and customary meaning, as would be understood by one of ordinary
skill in the art at the time of the invention. See In re Translogic Tech., Inc.,
504 F.3d 1249, 1257 (Fed. Cir. 2007).
i. “laminate” or “laminated”
Petitioner argues that the Specification of the ’494 patent does not
define the term “laminate” or “laminated.” Pet. 13. Petitioner does note that
the Specification of the ’494 patent teaches that multiple layers are placed on
the same drying fixture to create a laminate-type allograft material. Id. at 14
(citing Ex. 1001, 3:33–39). According to Petitioner, however, a person of
ordinary skill in the art would understand the verb “laminate” to mean
layering or uniting two layers, while the noun form would be understood as
referring to the resulting product. Id. at 13–14 (citing Ex. 1002 ¶ 37; Ex.
1014).
Patent Owner responds that laminate should be construed as
“separated and washed amnion and/or chorion layers that are adhered
together.” Prelim. Resp. 7. Patent Owner argues that the Specification of
the ’494 patent “expressly provides that the laminate is produced by
adhering two or more amnion and/or chorion layers on top of one another to
laminate the layers and thus create a single-unit multi-layer tissue graft.”
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Id. at 7–8 (citing Ex. 1001, 2:7–9, 2:45–55, 3:33–39, and 8:51–57).
According to Patent Owner, layers that do not adhere to one another would
not be able to form such a graft. Id. at 8. Finally, Patent Owner also points
to the claim language of claim 9, which recites “a laminate,” that is, Patent
Owner asserts, a single unit. Id. at 7.
For purposes of this Decision, we agree with Patent Owner, that
consistent with the Specification of the ’494, “laminate” or “laminated”
should be construed as requiring that the amnion and/or chorion layers be
adhered together. In particular, as taught by the ’494 patent, the resulting
dried laminate is cut and the resulting allograft is sealed in a pouch.
Ex. 1001, 9:22–23, 9:45–46. Petitioner does not explain how chorion and/or
amnion membranes that simply are layered on top of each other, but not
adhered together, would result in a cohesive product that can be cut to form
the tissue allograft.
ii. All Remaining Terms
We determine that, for purposes of this Decision, none of the other
terms in the challenged claims requires express construction at this time.
B. Principles of Law
In order for a prior art reference to serve as an anticipatory reference,
it must disclose every limitation of the claimed invention, either explicitly or
inherently. In re Schreiber, 128 F.3d 1473, 1477 (Fed. Cir. 1997). We must
analyze prior art references as a skilled artisan would. See Scripps Clinic &
Res. Found. v. Genentech, Inc., 927 F.2d 1565, 1576 (Fed. Cir. 1991)
(stating that to anticipate, “[t]here must be no difference between the
claimed invention and the reference disclosure, as viewed by a person of
ordinary skill in the field of the invention”), overruled on other grounds by
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Abbott Labs. v. Sandoz, Inc., 566 F.3d 1282 (Fed. Cir. 2009). “Inherency,
however, may not be established by probabilities or possibilities. The mere
fact that a certain thing may result from a given set of circumstances is not
sufficient.” In re Oelrich, 666 F.2d 578, 581 (CCPA 1981) (emphasis
added) (citation omitted).
A claim is unpatentable under 35 U.S.C. § 103(a) if the differences
between the subject matter sought to be patented and the prior art are such
that the subject matter as a whole would have been obvious at the time the
invention was made to a person having ordinary skill in the art to which said
subject matter pertains. KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 406
(2007). The question of obviousness is resolved on the basis of underlying
factual determinations including: (1) the scope and content of the prior art;
(2) any differences between the claimed subject matter and the prior art;
(3) the level of ordinary skill in the art; and (4) objective evidence of
nonobviousness. Graham v. John Deere Co., 383 U.S. 1, 17–18 (1966). An
invention “composed of several elements is not proved obvious merely by
demonstrating that each of its elements was, independently, known in the
prior art.” KSR, 550 U.S. at 418. Moreover, a determination of
unpatentability on the ground of obviousness must include “articulated
reasoning with some rational underpinning to support the legal conclusion of
obviousness.” In re Kahn, 441 F.3d 977, 988 (Fed. Cir. 2006). The
obviousness analysis “should be made explicit” and it “can be important to
identify a reason that would have prompted a person of ordinary skill in the
relevant field to combine the elements in the way the claimed new invention
does.” KSR, 550 U.S. at 418.
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C. Anticipation/Obviousness over Vishwakarma (Ex. 1005)
Petitioner asserts that claims 9 and 10 are unpatentable as being
anticipated, or rendered obvious, by Vishwakarma. Pet. 16–21.
i. Overview of Vishwakarma
Vishwakarma is drawn using an interposed, multi-layered cap of
amniotic membrane in arthroplasty of the hip. Ex. 1005, Abstract.
Vishwakarma teaches a method for preparing the amniotic cap. Id. at 69.
Specifically, Vishwakarma teaches:
The amniotic cap was prepared according to a technique
which has been standardized at this centre. Fresh placentae
were collected from the maternity centre and washed in running
tap water for 10 minutes. Amnion was separated from the
chorion, and amnion membrane, denuded of mucus, was
collected in a beaker containing normal saline. Layers were
then cut into squares and piled on a glass mould the size of a
femoral head. There were 50 to 60 layers in each cap, the
mesenchymal surface of the membrane always facing the glass
mould. The amniotic cap was dried at ambient temperature for
six to eight hours and a purse-string suture was then applied
. . . . The dried cap was sterilized in 1% β-propiolactone for
two hours before operation . . . .
Id. (citation omitted).
ii. Analysis
Petitioner asserts that claims 9 and 10 are unpatentable as being
anticipated, or rendered obvious, by Vishwakarma. Pet. 16–21. As support,
Petitioner relies on the Declaration of Dr. Daniel L. Mooradian (Ex. 1002),
as well as the Declaration of Dr. James W. Poser (Ex. 1017). Patent Owner
disagrees, relying on the deposition transcript of Dr. Mooradian (Ex. 2012).
Prelim. Resp. 26–34.
As to the requirement of claims 9 and 10 that the layers be “directly
laminated to each other,” Petitioner states that after separation of the
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placental tissue, “the amnion is collected or submerged in saline and then
laminated.” Pet. 17 (citing Ex. 1005, 69). Petitioner points also to the
teaching in Vishwakarma that the amniotic cap was dried at ambient
temperature for six to eight hours. Id. at 19 (claim chart).
Patent Owner argues that Vishwakarma does not disclose laminated
amnion layers. Prelim. Resp. 32. In particular, Patent Owner contends the
ordinary artisan, reading Vishwakarma, “would have understood that the
squares of amniotic membrane are simply ‘piled’ on the glass mold but are
not directly adhered to each other.” Id. at 32–33. In support, Patent Owner
points to the teaching of Vishwakarma that a purse string suture is applied to
hold the layers together, which would not be required if the layers had
adhered together. Id. at 33.
As discussed above, Vishwakarma teaches layering 50 to 60 squares
of amnion on a glass mold the size of a femoral head, which was then dried
at ambient temperature. Ex. 1005, 69. A purse string suture was then
applied. Id. at 69, Figure 1. Although it is possible that the amniotic layers
of Vishwakarma may have adhered to one another through cellular or tissue
interactions between the layers, inherency may not be established by mere
possibilities. Except for the disclosure that the 50 to 60 squares were
layered on a glass head and then dried, Petitioner points to no evidence, nor
provides any scientific reasoning, demonstrating that the layers of amnion
necessarily adhered to each other in the technique employed by
Vishwakarma. Thus, Petitioner has not demonstrated a reasonable
likelihood that Vishwakarma anticipates claims 9 and 10 of the ’494 patent.
As to the obviousness challenge, Petitioner asserts that it would have
been obvious to the ordinary artisan “that Vishwakarma retains the epithelial
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and fibroblast cell layers because Vishwakarma does not teach any methods
to remove those layers.” Pet. 20–21. Petitioner does not address, however,
why it would have been obvious to adhere the amnion layers of
Vishwakarma to produce a laminate.
iii. Conclusion
For the reasons set forth above, Petitioner has not established a
reasonable likelihood that claims 9 and 10 are anticipated, or rendered
obvious, by Vishwakarma.
D. Obviousness over Gray (Ex. 1006)
Petitioner contends that claims 1–10 are unpatentable as obvious over
Gray. Pet. 21–31.
i. Overview of Gray
Gray is drawn to “fetal membrane tubes for nerve and vessel grafts.”
Ex. 1006, 1:6–7. As taught by Gray, the grafts are prepared by obtaining
amnion and chorion from fresh placentas. Id. at 4:23–24. According to
Gray:
the amnion and chorion layers are separated from the placenta
and each other, cellular monolayer material overlying the basal
lamina on the fetal side of the membrane is removed, such as by
exposure to trypsin or pepsin, the amnion and chorion is rinsed
repeatedly with phosphate buffer solution-or distilled water
until clean, the amnion or chorion is then cross-linked either by
exposure to gamma radiation or chemical cross-linking such as
with glutaraldehyde, which sterilizes the tissue, provides
protection against viral disease transmission, strengthens and
permits remodeling the material from sheet to conduit form.
The amnion and chorion sheets are then wrapped in layers so
that the fetal surface, which is shiny, is directed toward the
inner surface of the finished tube. The number of wraps will
depend upon the length and diameter of the tube. The tubes are
then dried and placed in bottles which are sealed, labeled and, if
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desired, exposed to 2.5 M rads of gamma radiation to again
sterilize and further cross-link the conduit collagen. If desired,
the layers can be glued together by a suitable glue, such as a
fibrin glue, to prevent delaminating, particularly in larger
conduits, such as used for vascular grafts.
Id. at 4:25–5:9.
Gray teaches that it is also an object of the invention to provide a graft
that comprises a cylindrical wall formed by sheets of sterilized collagen,
Types I, II, and III, derived from human placenta from which the cellular
material has been substantially removed. Id. at 5:23–29.
ii. Analysis
Petitioner asserts that claims 1–10 are unpatentable as being rendered
obvious by Gray. Pet. 21–31. As support, Petitioner relies on the
Declaration of Dr. Mooradian (Ex. 1002). Patent Owner disagrees. Prelim.
Resp. 35–42.
Specifically, as to the issue of whether the grafts of Gray retain a
fibroblast or epithelial cell layer, Petitioner contends that while Gray teaches
the use of trypsin to remove the epithelial cellular layer, the ordinary artisan
would understand that treatment with trypsin “would be ineffective for
removing fibroblasts embedded in a three-dimensional extracellular such as
the fibroblast layer or spongy layer.” Pet. 22 (citing Ex. 1002 ¶ 60). In
addition, Petitioner cites claims 1 and 2 of Gray as representing an
embodiment in which “Gray teaches that cell layers are not removed.” Id. at
23.
Petitioner contends further that the ordinary artisan would understand
that “Gray specifically teaches the removal of the epithelial layer to promote
axon growth and not for anything related to the lamination or dehydration
processing steps.” Id. at 22–23 (citing Ex. 1002 ¶ 61). In particular,
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Petitioner argues that the ordinary artisan would understand that “Gray’s
disclosure of removing the epithelial layer as important for nerve grafts but
not necessary or important for blood vessel grafts.” Id. at 24 (citing
Ex. 1002 ¶ 60).
Petitioner concludes, therefore, that the ordinary artisan would
understand that not all applications of placental tissue grafts would require
exposure of the basement membrane, and would be motivated to modify the
method of Gray to allow for retention of the epithelial cell layer, which
would simplify and shorten processing of the graft. Id. at 24–25 (citing Ex.
1002 ¶¶ 61-62).
Patent Owner responds that because Gray teaches that “the collagen
tubes of the invention are processed such that ‘cellular material is
substantially removed,’ one of ordinary skill in the art reading Gray would
have understood that the goal of the invention was decellularization of the
amniotic and chorionic membranes.” Prelim. Resp. 35 (citing Ex. 1006,
5:23–35, 12:23–35). In particular, Patent Owner argues that Petitioner only
provides an unsupported assertion that the methods of Gray would not
remove the fibroblast cells or the fibroblast cell layer, but no evidence in
support of that assertion. Id. at 36. Moreover, Patent Owner contends that
the only motivation to modify Gray provided by Petitioner is to simplify the
processing, but Gray provides a specific reason to decellularize the layers,
which is to reduce immunogenicity. Id. at 37–38.
We agree with Patent Owner that Petitioner has not established a
reasonable likelihood that claims 1–10 are rendered obvious by Gray.
Notably, we agree with Patent Owner that Gray teaches a graft comprising
sheets of sterilized collagen, Types I, II, and III, derived from human
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placenta, and from which the cellular material has been substantially
removed. Ex. 1006, 5:23–29.
We have considered the disclosure of claims 1 and 2 of Gray, as well
as the Declaration of Dr. Mooradian, but they do not convince us otherwise.
The claims of Gray must be read in light of the disclosure, and Petitioner
does not point us to any teaching, nor to any claim, that specifies that the
fibroblast cell layer is retained in the placental graft of Gray. Nor does
Petitioner points us to any additional decellularization step in Gray that is
used to remove the fibroblast cell layer.
Petitioner relies on the Declaration of Dr. Mooradian to support its
assertion that the use of trypsin or pepsin will not remove the fibroblast cell
layer. Pet. 22. Dr. Mooradian, however, merely provides the conclusory
statement that the ordinary artisan would understand that trypsin acts by
disrupting the attachment of cells to the extracellular matrix, and thus, while
trypsin may be used to remove epithelial cells, “it would be ineffective for
the purpose of removing fibroblasts embedded in a three-dimensional matrix
such as would be found in the fibroblast layer or spongy layers of the
amnion.” Ex. 1002 ¶ 60. Dr. Mooradian does not provide any evidence to
support that statement, and that statement is, thus, entitled to little weight.
37 C.F.R. § 42.65(a). Moreover, Dr. Mooradian does not address the
statement in Gray that the graft comprises sheets of sterilized collagen,
Types I, II, and III, derived from human placenta from which the cellular
material has been substantially removed. Ex. 1006, 5:23–29.
iii. Conclusion
For the reasons set forth above, Petitioner has not established a
reasonable likelihood that claims 1–10 are rendered obvious by Gray.
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E. Obviousness over the Combination of Gray (Ex. 1006)
and Vishwakarma (Ex. 1005)
Petitioner contends that claims 1–10 are unpatentable as obvious over
Gray and Vishwakarma. Pet. 31–36. As support, Petitioner relies on the
Declaration of Dr. Mooradian (Ex. 1002). Patent Owner disagrees. Prelim.
Resp. 42–47.
The disclosures of Gray and Vishwakarma are discussed above.
According to Petitioner, “Vishwakarma discloses a simplified method of
placenta processing resulting in a dehydrated, non-decelled laminate
comprised of amnion,” and “Gray teaches a more complex method of
processing that includes additional washing, treatment to reduce infection
potential, and partial decellularization that results in a dehydrated laminate
comprised of amnion and/or chorion.” Pet. 31.
Petitioner contends that the ordinary artisan would understand that the
removal of cells, such as the epithelial cellular layer, is not required in
preparing placental cell grafts unless there is a need to do so. Id. (citing Ex.
1002 ¶ 65). Petitioner relies on Vishwakarma for teaching that both
lamination and dehydration are viable with amnion that has not been
decellularized, arguing that it would have been obvious “to include the more
substantial washing steps and treatment with a sterilant of Gray into the
processing of Vishwakarma to reduce infection potential without impacting
the capability of the non-decelled tissue to be laminated or dehydrated.” Id.
at 31–32.
Patent Owner responds that Petitioner has not provided a reason to
combine Gray with Vishwakarma, as the invention of Gray is premised on
the decellularization of the amniotic and/or chorionic membranes. Prelim.
Resp. 43. Instead, according to Patent Owner, Petitioner and its declarant
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state, without relying on any supporting evidence, that it would be obvious
to eliminate the decellularization step. Id.
We agree with Patent Owner that Petitioner has not demonstrated a
reasonable likelihood that the combination of Gray and Vishwakarma
renders claims 1–10 obvious. Petitioner relies on Vishwakarma as
demonstrating that lamination and dehydration are viable with amnion that
has not been decellularized. Pet. 31. As discussed above as to the challenge
of claims 9 and 10 as being anticipated or rendered obvious by
Vishwakarma, however, Petitioner has not demonstrated that Vishwakarma
provides a laminate in which the layers are adhered together. Moreover,
while Gray does teach a laminate, Petitioner and Dr. Mooradian only
provide a conclusory statement, without any articulated reasoning, that it
would have been obvious to retain the cells on the graft of Gray.
“[O]bviousness grounds cannot be sustained by mere conclusory statements;
instead, there must be some articulated reasoning with some rational
underpinning to support the legal conclusion of obviousness.” Kahn, 441
F.3d at 988.
iii. Conclusion
For the reasons set forth above, Petitioner has not established a
reasonable likelihood that claims 1–10 are rendered obvious by the
combination of Gray and Vishwakarma.
F. Obviousness over the Combination of Tseng (Ex. 1008)
and Miljudin (Ex. 1007)
Petitioner contends that claims 9 and 10 are unpatentable as obvious
over Tseng and Miljudin. Pet. 36–41.

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i. Overview of Tseng (Ex. 1008)
Tseng is drawn to “amniotic membrane grafts especially usable in the
repair of injured eyes.” Ex. 1008, 1:14–15. In preparing the graft, placenta
is rinsed with balanced saline, which preferably contains antibiotics, to
remove excessive blood clots. Id. at 4:60–65. While immersed in the
solution, the amnion is separated from the chorion by blunt dissection. Id. at
5:7–10. The separated amniotic sheet is then mounted on a substrate, such
as a sterile nitrocellulose paper, such that the epithelial surface is kept facing
up, and the stromal/fibroblastic surface is layered on the substrate. Id. at
5:10–14. According to Tseng, when used as a surgical graft to treat
ulceration of the eye, the amniotic membrane is peeled off the substrate. Id.
at 6:16–31. Tseng teaches further that one layer is generally sufficient, but
that “it is also feasible to use two or more layers.” Id. at 6:38–39.
ii. Overview of Miljudin (Ex. 1007)
Miljudin looked at the properties of amniotic membrane treated with
antibiotics, dried over silica gel, and then sterilized by gamma rays.
Ex. 1009, Abstract. Specifically, placentas are collected, and amnion is
separated from chorion that has been washed free of blood clots. Id. at 272.
The amniotic membrane is treated with glycerol, and fixed on frames over
silica gel for 18 to 24 hours, and then sterilized by gamma rays. Id. at 272–
273. The amniotic membrane still has epithelial cells, although there is a
decrease in their number, and they have lost their “vital capacity.” Id. at
273.
ii. Analysis
Petitioner asserts that claims 9 and 10 are unpatentable as obvious
over Tseng and Miljudin. Pet. 36–41. As support, Petitioner relies on the
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Declaration of Dr. Mooradian (Ex. 1002). Patent Owner disagrees. Prelim.
Resp. 47–51.
As to the requirement of a laminated, placental tissue graft, Petitioner
relies on the teaching in Tseng that two or more layers of an amnion tissue
graft may be used to fill deep ulcerations, and contends that the layering of
multiple amnion membranes creates a laminate. Pet. 37 (relying on Ex.
1008, 6:18–39; Ex. 1002 ¶ 74); see also id. at 39 (claims chart pointing to
support for laminate). Petitioner argues that it would have been obvious to
use the dehydration and processing steps of Miljudin with the multi-layer
laminate of Tseng, which would allow for the elimination of the need for
nitrocellulose paper and freezer based storage. Id. at 39 (citing Ex.
1002 ¶ 76).
Patent Owner responds that Petitioner has not established that Tseng
and Miljudin, either separately or combined, teach a placental tissue graft in
which the layers are directly laminated to one another. Prelim. Resp. 47–48.
According to Patent Owner, both Tseng and Miljudin are drawn to single
layer grafts, and although the grafts of Tseng may be layered, Dr. Mooradian
admits that the layers are not adhered to one another. Id. at 50–51 (citing
Ex. 1002 ¶ 74).
We agree with Patent Owner that Petitioner has not demonstrated a
reasonable likelihood that the combination of Tseng and Miljudin renders
claims 9 and 10 obvious. Specifically, Petitioner relies on the teaching of
Tseng that two or more layers of a placental graft may be layered to treat
deep ulcerations. We have construed the term “laminated” as requiring the
layers to be adhered together. Petitioner has provided no evidence or
scientific reasoning as to how layering two or more placental grafts in a deep
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ulceration would necessarily result in the layers adhering together to form a
laminate. Nor has Petitioner provided evidence or scientific reasoning that it
would have been obvious based on Tseng’s and Miljudin’s teachings to
create a laminate by adhering the layers.
iii. Conclusion
For the reasons set forth above, Petitioner has not established a
reasonable likelihood that claims 9 and 10 are rendered obvious by the
combination of Tseng and Miljudin.
G. Obviousness over the Combination of Hariri (Ex. 1009)
and Vishwakarma (Ex. 1005)
Petitioner contends that claims 1–10 are unpatentable as obvious over
Hariri and Vishwakarma. Pet. 41–53.
i. Overview of Hariri (Ex. 1009)
Hariri is drawn to a collagen biofabric produced from amnion. Ex.
1009 ¶ 2. The collagen biofabric is prepared by decellularizing the amniotic
membrane, and preferably, the membrane is completely decellularized. Id.
In the method of Hariri, the amniotic membrane is separated from the
chorionic membrane. Id. at ¶ 80. The membrane is then decellularized to
remove substantially all of the cells normally associated with the collagen
matrix, preferably by using a weak detergent solution. Id. at ¶¶ 83, 86.
After additional washing steps to remove any cellular debris, the membrane
is dried, preferably under vacuum. Id. at ¶¶ 93, 101.
Hariri also discloses the production of laminates. Id. at ¶ 113. The
laminates may be prepared by layering the decellularized membrane, and
then drying the layered membrane, or by layering the dried membrane. Id.
at ¶¶ 115–116. Hariri also teaches the use of an adhesive or cross-linking to
prepare the laminate. Id. at ¶ 117.
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Hariri specifically compares the use of decellularized grafts with
grafts that may have dead cells present, concluding that anecdotal evidence
is suggestive that when dead cells are present, healing times are longer and
rejection rates are higher. Id. at Table 1.
ii. Analysis
Petitioner asserts that claims 1–10 are unpatentable as being rendered
obvious by the combination of Hariri and Vishwakarma. Pet. 41–53. As
support, Petitioner relies on the Declaration of Dr. Mooradian (Ex. 1002).
Patent Owner disagrees, relying on the deposition transcript of
Dr. Mooradian (Ex. 2012). Prelim. Resp. 51–56.
An overview of Vishwakarma is presented above. Petitioner contends
that Hariri alone renders obvious claims 1–10, as “[w]ithout a specific
reason to decellularize,” the ordinary artisan would have eliminated that step
of Hariri “to simplify processing and shorten the time required.” Pet. 44
(citing Ex. 1002 ¶ 86). In the alternative, Petitioner contends that it would
have been obvious to a person of ordinary skill in the art to use non-decelled
placental tissue as taught by Vishwakarma, with the lamination techniques
and gross processing of Hariri, as Vishwakarma teaches lamination of at
least two layers on non-decelled amnion tissue with subsequent drying,
demonstrating that lamination is possible with non-decelled tissue. Id. at 44.
Patent Owner contends that the only reason provided by Petitioner to
combine Vishwakarma with Hariri is to simplify processing by removing the
decellularization step, which Petitioner characterizes as unnecessary.
Prelim. Resp. 51–52. Patent Owner argues, however, that the
decellularization step of Hariri, resulting in a collagen matrix that is devoid
of cells, allows for the transportation of biomolecules or living cells. Id. at
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52 (citing Ex. 1002 ¶ 86). In addition, Patent Owner argues that “Hariri also
states that evidence suggests that even the presence of dead cells may have
negative consequences, leading to a higher rejection rate and longer healing
time.” Id. (citing Ex. 1009, Table 1).
We agree with Patent Owner that Petitioner has not demonstrated a
reasonable likelihood that the combination of Hariri and Vishwakarma
renders claims 1–10 of the ’494 patent obvious. As to Petitioner’s argument
that it would have been obvious to not remove the cells layers in producing
the placental graft of Hariri without a specific reason to do so, we find that
to be a conclusory statement without sufficient support to conclude that
Petitioner has demonstrated a reasonable likelihood of obviousness. Kahn,
441 F.3d at 988. Moreover, as noted by Patent Owner, Table I of Hariri
provides reasons why decellularized grafts are advantageous over grafts in
which dead cells may be present. And as acknowledged by Dr. Mooradian,
Hariri teaches that the cells are removed so that the collagen matrix can
transport biomolecules or living cells. Ex. 1002 ¶ 86.
As to the combination of Hariri with Vishwakarma, Petitioner has not
demonstrated that Vishwakarma provides a laminate in which the layers are
adhered together, and thus, does not demonstrate that lamination is possible
with non-decelled tissue. Thus, Vishwakarma does not add anything to
Hariri to support Petitioner’s contention of obviousness.
iii. Conclusion
For the reasons set forth above, Petitioner has not established a
reasonable likelihood that claims 1–10 are rendered obvious by the
combination of Hariri and Vishwakarma.

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H. Obviousness over the Combination of Gray (Ex. 1006)
and Miljudin (Ex. 1007) or Tseng (Ex. 1008)
Petitioner contends that claims 3, 9, and 10 are unpatentable as
obvious over Gray and Miljudin or Tseng. Pet. 53–58. As support,
Petitioner relies on the Declaration of Dr. Mooradian (Ex. 1002). Patent
Owner disagrees. Prelim. Resp. 56–58.
The disclosures of Gray, Miljudin, and Tseng are discussed above.
Petitioner relies on Miljudin and/or Tseng for the teaching of the use of
antibiotics to treat amnion prior to use, contending that it would have been
obvious to the ordinary artisan to treat the separated amnion and chorion
layers of Gray with antibiotics prior to lamination. Pet. 53 (citing Ex. 1002
¶¶ 92–93. Petitioner does not explain, however, how either Miljudin or
Tseng remedies the deficiencies of Gray as set forth in Section II(D) above.
iii. Conclusion
For the reasons set forth above, Petitioner has not established a
reasonable likelihood that claims 3, 9, and 10 are rendered obvious by the
combination of Gray and Tseng or Miljudin.
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CONCLUSION III.
For the foregoing reasons, we are not persuaded that the Petition
establishes a reasonable likelihood that Petitioner would prevail in showing
any of claims 1–10 of the ’494 patent are unpatentable under 35 U.S.C.
§ 102(b) or 35 U.S.C. § 103(a).
ORDER IV.
In consideration of the foregoing, it is hereby:
ORDERED that the Petition is denied as to all of the challenged
claims of the ’494 patent.

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PETITIONER:
Robert McRae
Jason McKinnie
GUNN, LEE & CAVE, PC
rmcrae@gunn-lee.com
jmckinnie@gunn-lee.com

PATENT OWNER:
Keith E. Broyles
Thomas J. Parker
Christopher T. L. Douglas
ALSTON & BIRD LLP
Keith.Broyles@alston.com
Thomas.Parker@alston.com
Chris.Douglas@alston.com