Advanced Medical Technologies LLC

Patent Trials and Appeals Board

Dec 28, 2020

2020002146 (P.T.A.B. Dec. 28, 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.
13/962,241 08/08/2013 Pete O'Heeron AMTK.P0004US 4724
26271 7590 12/28/2020
NORTON ROSE FULBRIGHT US LLP
1301 MCKINNEY
SUITE 5100
HOUSTON, TX 77010-3095
EXAMINER
CLARKE, TRENT R
ART UNIT PAPER NUMBER
1651
NOTIFICATION DATE DELIVERY MODE
12/28/2020 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):
hoipdocket@nortonrosefulbright.com
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
_________________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
_________________

Ex parte PETE O’HEERON

_________________

Appeal 2020-002146
Application 13/962,241
Technology Center 1600
_________________

Before ERIC B. GRIMES, RAE LYNN P. GUEST, and
DEBORAH KATZ, Administrative Patent Judges.

KATZ, Administrative Patent Judge.

DECISION ON APPEAL
Appellant1 seeks our review2, under 35 U.S.C. § 134(a), of the
Examiner’s decision to reject claims 1 and 4–19. We have jurisdiction under
35 U.S.C. § 6(b). We AFFIRM.

1 We use the word “Appellant” as defined in 37 C.F.R. § 1.42. Appellant
identifies the real party-in-interest as Advanced Medical Technologies LLC.
(Appeal Br. 3.)
2 We consider the Non-Final Office Action issued October 12, 2018 (“Non-
Final Act.”), the Appeal Brief filed June 12, 2019 (“Appeal Br.”), the
Examiner’s Answer issued on November 27, 2019 (“Ans.”), and the Reply
Brief filed January 21, 2020 (“Reply Br.”) in reaching our decision.
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Appellant’s Specification is directed to methods for growing,
proliferating, and/or differentiating cells, including human dermal fibroblasts
(“HDFs”), into chondrocyte-like cells under mechanical stress for the
production of cartilage ex vivo, which is then placed in vivo in an individual.
(Spec. ¶ 5.) Appellant’s Specification explains that MRI or CT scans can be
used to generate a three-dimensional mold of the desired cartilage shape,
which is seeded with human dermal fibroblasts in the present invention.
(See id. ¶ 16.) The mold is then subjected to conditions that facilitate
generation of chondrocytes from fibroblasts, including low oxygen and
mechanical stress, and once the tissue is generated, it can be placed in the
body at the appropriate location. (See id. ¶ 16.)
Appellant’s claim 1 recites:3
A method of generating cartilage ex vivo, comprising the
steps of:
subjecting human fibroblasts ex vivo to conditions to
differentiate said fibroblasts into chondrocyte-like cells that
form cartilage ex vivo in a desired shape,
wherein said conditions comprise mechanical stress or
both mechanical stress and low oxygen of <5%, wherein the
method occurs in the absence of bone morphogenetic protein 2
(BMP-2), and
wherein the fibroblasts are dermal fibroblasts, tendon
fibroblasts, ligament fibroblasts, synovial fibroblasts, foreskin
fibroblasts, or a mixture thereof.

(Appeal Br. 10.)

3 Claim 1 has been modified by adding indentations to separate elements.
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The Examiner rejected claims 1, 7, 8 and 12–19 under 35 U.S.C.
§ 102(b) as being anticipated by Sevrain.4 (See Ans. 3–4.) In addition, the
Examiner rejected claims 1, 4–8 and 12–19 under 35 U.S.C. § 103(a) as
being obvious over Bhatnagar,5 Sevrain, and Bonassar6 (Ans. 5–9) and
claims 1 and 4–19 also under 35 U.S.C. § 103(a) as being obvious over
Bhatnagar, Sevrain, Bonassar, and Antonyshyn7 (Ans. 9–11). A rejection
under 35 U.S.C. § 112, first paragraph, for lack of a sufficient written
description was withdrawn in the Examiner’s Answer. (See Ans. 11–12.)
Appellant does not argue for the separate patentability of any of the
claims rejected under any of these grounds. (See Appeal Br. 7 and 8.) We
focus on claim 1 in our review. See 37 C.F.R. § 41.37(c)(1)(iv).

35 U.S.C. § 102 – Sevrain
Sevrain teaches methods and compositions for biological repair of any
kind of cartilage using a combination of an inert structure, which acts as an
in vivo bioreactor, and a living structure comprised of chondrocytes or
chondrocyte-like cells, such as cells derived from human dermal fibroblasts
(HDFs). (See Sevrain ¶ 21.) Sevrain teaches that the inert structure acts not
only as a delivery system to feed and grow a living core component, but also
acts as an inducer of cell differentiation. (See Sevrain ¶ 21.) Sevrain

Claim 1 has been modified by adding indentations to separate elements.
033 A1, published August 9, 2007.
5 Bhatnagar and Nicoll, U.S. Patent 6,197,586 B1, issued March 6, 2001.
6 Bonassar et al., U.S. Patent Application Publication 2002/0159982 A1,
published October 31, 2002.
7 Antonyshyn et al., U.S. Patent Application Publication 2012/0010711 A1,
published January 12, 2012.
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explains further that the inert structure comprises two expandable balloon-
like bio-polymers: an internal membrane (like a balloon) that is enclosed
within an external membrane (also like a balloon), creating two generally
concentric inflatable membranes that may be generally spherical but are
individual-specific and conform to the shape and size of the remaining
cavity in the joint or intervertebral disc region of the individual. (Sevrain ¶
21.)
Sevrain teaches
In certain aspects, the invention generates natural tissue in vitro,
such as from stem cells, chondrocytes, and so forth. More
particularly, but not exclusively, the present invention relates to
a method for growing and differentiating Human Fibroblasts
into chondrocyte-like cells, for example. The cells, which are
autologous in certain embodiments, are put into a scaffold
matrix made of one or more biopolymers, such as to mimic a
natural matrix. The scaffold may be seeded in vitro, and in
certain aspects growth factors are provided to the cells, the
matrix, or both. The scaffold is put into a bioreactor, which is a
system for perfusion of medium and allows application of
mechanical force to the scaffold. Following delivery of the
force, cells are assisted in differentiation, especially for
generation of cartilage.

(Sevrain ¶ 22.)
We agree with the Examiner that Sevrain teaches differentiating
HDFs into chondrocytes to generate cartilage in vitro. (See Ans. 3, citing
Sevrain ¶ 22.) We also agree that Sevrain teaches such differentiation under
conditions of mechanical stress and low oxygen of <5%. (See Ans. 3, citing
Sevrain ¶ 23 (“In specific embodiments, factors that mimic the in vivo
environment of intervertebral chondrocytes are potent stimuli for
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chondrogenic differentiation of HDFs, for example; such factors include the
following: 1) three dimensionality; 2) low oxygen tension (<5%); and 3)
mechanical stress . . . .”) We agree further that Sevrain teaches
differentiation in the absence of bone morphogenetic protein 2 (BMP-2).
(See Ans. 3–4, citing Sevrain claim 54 (“A method of preparing a
cells/scaffold composition, wherein the cells are chondrocytes or
chondrocyte-like cells, comprising: subjecting cells capable of
differentiating into a chondrocyte-like cell to the scaffold; subjecting the
cells to mechanical stress; and optionally subjecting the cells to one or more
growth factors suitable for differentiation to a chondrocyte or chondrocyte-
like cell.”).
Appellant argues that Sevrain does not teach a method of generating
cartilage ex vivo that includes “subjecting human fibroblasts ex vivo to
conditions to differentiate said fibroblasts into chondrocyte-like cells that
form cartilage ex vivo in a desired shape,” as recited in claim 1 because
Sevrain teaches using a device designed to conform to the shape of a cavity,
not forming cartilage in a desired shape ex vivo. (See Appeal Br. 5–6, citing
Sevrain ¶ 21 and ¶ 101 (“[i]n specific embodiments, the device conforms to
the shape of the cavity.”).) Appellant argues further that any particular
shape taken by the device is taken only after insertion into a subject and,
therefore, is taken in vivo, not ex vivo. (See Reply Br. 3.)
Appellant’s argument relies on an interpretation of claim 1 wherein
the phrase “subjecting human fibroblasts ex vivo to conditions to
differentiate said fibroblasts into chondrocyte-like cells that form cartilage
ex vivo in a desired shape,” excludes methods that use an implanted device
or scaffold that assumes the shape of a cavity when inserted into a patient.
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We are persuaded that the broadest reasonable interpretation of claim 1
excludes such an embodiment. See In re American Academy of Sci. Tech
Center, 367 F.3d 1359, 1364 (Fed. Cir. 2004) (“During examination, ‘claims
. . . are to be given their broadest reasonable interpretation consistent with
the specification, and . . . claim language should be read in light of the
specification as it would be interpreted by one of ordinary skill in the art.’”
(quoting In re Bond, 910 F.2d 831, 833 (Fed. Cir. 1990)).
We look to Appellant’s Specification for an understanding of the
phrase regarding forming cartilage ex vivo in a desired shape. In the
Summary of Claimed Subject Matter, Appellant states:
The desired shape may be part or all of an ear or nose
(Originally filed Specification at paras. [0008][0009] and
[0016] and claims 4-5). Certain methods of generating the
desired shape are encompassed, including generating a mold of
the desired shape, which may be facilitated by imaging a part of
the body of an individual that is or is not in need of cartilage
repair (Originally filed Specification at Abstract, paras. [0016]
and [0048], and claims 6-8.). The desired shape may be
provided to an individual (e.g., to a nose, ear, knee, shoulder,
elbow, or other area of the body), and may replace or repair
cartilage in one of more regions of the body of an individual
requiring connective tissue (Originally filed Specification at
paras. [0012] and [0016] and claims 9-11). A desired shape
may be provided to an individual with one or more supports,
which may be resorbable (e.g., may be comprised of a material
that is resorbed by the body of the individual) or may not be
resorbable (Originally filed Specification at paras. [0016],
[0025], and [0042] and claims 12-15). A desired shape may or
may not be delivered to a joint or vertebral disc (Originally
filed Specification at paras. [0012], [0023], [0033], and [0046]
and claims 18-19).

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(Amended Appeal Br. filed July 16, 2019, 3.) In portions cited by
Appellant, the Specification provides means to produce a desired shape by,
for example, imaging the defective cartilage with MRI or CT to generate a
mold of the shape and seeding fibroblasts in the mold. (See Spec. ¶ 48.)
The Specification does not provide for a balloon-like scaffold that
conforms to the shape and size of a cavity remaining from the removal of
damaged cartilage. Instead, the Specification discusses molds that are
designed to hold their own shape even when not located in the patient.
Thus, we agree with Appellant that claim 1 excludes methods using an
implanted device or scaffold that assumes the shape of a cavity when
inserted into a patient and fails to have its own shape outside of the patient.
Because the method taught in Sevrain uses such excluded methods, rather
than a mold that assumes its own shape without being inserted into the
patient, we agree with Appellant that Sevrain does not teach each and every
limitation of claim 1.
Accordingly, we agree with Appellant that Sevrain does not anticipate
Appellant’s claim 1 or the claims that depend on it.
35 U.S.C. § 103 – Bhatnagar, Sevrain, and Bonassar
Bhatnagar teaches treating fibroblast cells with an inhibitor of protein
kinase C along with hypoxic culture (oxygen tension between 1 and 7.5%) to
induce chondrogenic differentiation and allow for seeding on three-
dimensional polymer scaffolds for use in repair of articular cartilage lesions.
(Bhatnagar abstract, 4:17–34; see Ans. 5–6.) Like Sevrain, Bhatnagar
teaches that the fibroblasts can be HDFs. (See Bhatnagar 3:60–67; see Ans.
5.) Unlike Sevrain, though, Bhatnagar teaches differentiating HDFs into
chondrocyte-like cells on a mesh scaffold that “can be adapted in size and
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shape for use in repairing cartilage.” (Bhatnagar 9:35–36; see Ans. 5.)
Bhatnagar teaches further that the mesh scaffold is made of material that
forms a matrix “to allow repair cells to populate and proliferate within the
matrix and which can be degraded and replaced with cartilage during the
repair process.” (Bhatnagar 9:45–49; see Ans. 5.) Thus, Bhatnagar teaches
subjecting human dermal fibroblasts to conditions allowing for
differentiation of fibroblasts into chondrocyte-like cells that form cartilage
ex vivo in a desired shape, wherein the conditions include low oxygen, as
recited in Appellant’s claim 1.
The Examiner finds that Bhatnagar fails to teach using mechanical
stress to induce fibroblasts to differentiate into chondrocyte-like cells. (See
Ans. 6.) But the Examiner finds that those of ordinary skill in the art would
have combined the teachings of Bhatnagar and Sevrain, which teaches using
mechanical stress, along with low oxygen, to generate cartilage from HDFs
in vitro. (See Ans. 6, citing Sevrain ¶¶ 22–24, 123 (“IHP [intermittent
hydrostatic pressure] can also induce chondrogenic differentiation of HDFs.
It is known that HDFs can differentiate into chondrocyte-like cells under low
oxygen tension. Therefore, in accordance with an embodiment of the present
invention, mechanical stress, especially IHP and shear fluid stress, induce
chondrogenic differentiation of fibroblasts cultured in a three dimensional
matrix and low oxygen tension, for example.”).) The Examiner determines
that the method of Appellant’s claim 1 would have been obvious. (See Ans.
6–7.)
Appellant argues that Bhatnagar fails to teach or suggest “subjecting
human fibroblasts ex vivo to conditions to differentiate said fibroblasts into
chondrocyte-like cells that form cartilage ex vivo in a desired shape,” as
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recited in claim 1. (Appeal Br. 6.) Appellant quotes Bhatnagar to argue that
in the method it teaches “fibroblasts are first converted to chondrocyte-like
cells by treating with a combination of agents” and that the “chondrocyte-
like cells of the invention are preferably used . . . by being placed in a
suitable matrix in the desired site for repair.” (See Appeal Br. 6–7, quoting
Bhatnagar 2:53–55 and 3:22–24.) According to Appellant, Bhatnagar
teaches converting fibroblasts to chondrocyte-like cells only before being
placed on a matrix to create a desired shape of cartilage.
We are not persuaded by this argument because Appellant does not
accurately represent the full teachings of Bhatnagar. Instead of teaching
conversion to chondrocyte-like cells before culturing them on a matrix to
achieve cartilage for repair, Bhatnagar teaches:
The initial conversion of chondrocyte-like cells is preferably
where the cells are cultured in a high density micromass with
conversion occurring in a period occurring from about 12 hours
up to about 36 hours. The high density micromass culture is
preferably achieved on a biocompatible (preferably
biodegradable) scaffold. Such a scaffold assists in creating the
high density micromass and can subsequently serve as a
template for cartilage repair. The so-converted cells, when
attached to a scaffold, can thereafter be maintained with the
chondrocyte phenotype for about one to two weeks prior to
implantation by maintaining them in a chemically defined,
serum-free media.
(Bhatnagar 3:1–32; see Ans. 5.) Thus, Bhatnagar teaches that induction of
fibroblasts to become chondrocyte-like cells is “preferably achieved on a
biocompatible (preferably biodegradable) scaffold.” (Id.) Bhatnagar
teaches further that the matrix is adapted in size and shape for use in
repairing cartilage and allows repair cells to populate and proliferate within
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it and eventually to degrade it when being replaced with cartilage in the
repair process. (See id. 9:35–49.) Appellant fails to explain how these
portions of Bhatnagar fail to teach the step of claim 1 of “subjecting human
fibroblasts ex vivo to conditions to differentiate said fibroblasts into
chondrocyte-like cells that form cartilage ex vivo in a desired shape. . . .”
(Appeal Br. 10.)
In the Reply Brief, Appellant argues that “Bhatnagar says only, at
most, that its cells are useful for modification of nasoseptal and ear cartilage,
which in no way teaches or suggests the formation of cartilage, ex vivo, in a
desired shape, such as part or all of an ear (as recited in claim 4) or part or
all of a nose (as recited in claim 5).” (Reply Br. 4.) Appellant argues further
that Bhatnagar fails to teach forming mesh scaffolds into a desired shape
such as an ear or nose. (See id. 5.) Because Appellant failed to argue for the
separate patentability of claim 4 or 5 in the Appeal Brief and raises these
arguments for the first time in the Reply Brief, we consider this argument
only in regard to the argument that Bhatnagar teaches converting fibroblasts
to chondrocyte-like cells before being placed on a matrix to create a desired
shape of cartilage. As explained above, given the teaching of using a
scaffold in the conversion to chondrocyte-like cells, which is subsequently
degraded and replaced with cartilage, we are not persuaded that Bhatnagar is
deficient. (Bhatnagar 3:1–32 and 9:35–49; see Ans. 5.)
Appellant argues further that Bonassar fails to cure the deficiencies of
Bhatnagar, but because we are not persuaded of any deficiency, we are not
persuaded that the Examiner erred. (See Appeal Br. 7.) We note that
Bonassar was cited for its teaching of molds that can be used to form
cartilage in a desired shape, such as an ear or nose, in regard to Appellant’s
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claims 4 and 5. (See Bonassar ¶ 30 (“In some embodiments, the construct is
a precisely shaped piece of cartilage for the reconstruction of an external
anatomical structure, e.g., a nose or an ear.”); see Ans. 8.) Thus, even if we
were to consider Appellant’s argument in the Reply Brief that Bhatnagar
fails to teach formation of cartilage ex vivo in the desired shape of an ear or
nose, we would not be persuaded that the Examiner’s rejection was in error,
in light of the teachings of Bonassar.
In light of the entirety of Bhatnagar, we are not persuaded by
Appellant’s argument that the combination of the teachings of Bhatnagar,
Sevrain, and Bonassar fails to render the method of Appellant’s claim 1
obvious. Accordingly, we are not persuaded that the Examiner erred in
rejecting claim 1 under 35 U.S.C. § 103. Because Appellant fails to argue
separately in the Appeal Brief for the patentability of any of the claims that
depend on claim 1, we are also not persuaded that the Examiner erred in
rejecting them over the combination of the three cited references.
35 U.S.C. § 103 – Bhatnagar, Sevrain, Bonassar, and Antonyshyn
The Examiner rejected claims 1 and 4–19 as being obvious over
Bhatnagar, Sevrain, Bonassar, and Antonyshyn. (See Ans. 9–11.) Appellant
argues only that Antonyshyn fails to cure the deficiencies of Bhatnagar,
Sevrain, and Bonassar. (See Appeal Br. 8.) Because Appellant does not
persuade us of any deficiency in the teachings of these three references to
render claim 1 obvious, we are not persuaded that the rejection in light of
them along with Antonyshyn was made in error.
Conclusion
Upon consideration of the record and for the reasons given, we affirm
the Examiner’s rejection.
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In summary:
Claims
Rejected
35 U.S.C. § Basis Affirmed Reversed
1, 7, 8, 12–19 102(b) Sevrain 1, 7, 8, 12–19
1, 4–8, 12–19 103(a) Bhatnagar,
Sevrain,
Bonassar
1, 4–8, 12–19
1, 4–19 103(a) Bhatnagar,
Sevrain,
Bonassar,
Antonyshyn
1, 4–19
Overall
Outcome
1, 4–19

No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136.

AFFIRMED