Ex Parte Atala et al

Patent Trial and Appeal Board

Oct 14, 2015

11083602 (P.T.A.B. Oct. 14, 2015)

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.
11/083,602 03/18/2005 Anthony Atala 105447-0005 8006
21269 7590 10/14/2015
PEPPER HAMILTON LLP
500 GRANT STREET
SUITE 5000
PITTSBURGH, PA 15219-2507
EXAMINER
SCHLIENTZ, LEAH H
ART UNIT PAPER NUMBER
1618
MAIL DATE DELIVERY MODE
10/14/2015 PAPER
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.
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte ANTHONY ATALA, SHAY SOKER, JAMES YOO,
JOEL STITZEL, RICHARD CZERW, and GRACE LIM
__________

Appeal 2013-002581
Application 11/083,602
Technology Center 1600
__________

Before DEMETRA J. MILLS, ERIC B. GRIMES, and
ROBERT A. POLLOCK, Administrative Patent Judges.

MILLS, Administrative Patent Judge.

DECISION ON APPEAL

This is an appeal under 35 U.S.C. § 134. The Examiner has rejected
the claims for obviousness. We have jurisdiction under 35 U.S.C. § 6(b).
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STATEMENT OF CASE
The following claim is representative.
1. An electrospun matrix having a three-dimensional ultrastructure
of interconnected fibers and pores to permit cell attachment
comprising a vascular construct and further comprising an
internal MRI image enhancing agent embedded within the
electrospun matrix in a concentration sufficient for imaging of
the matrix, wherein the MRI image enhancing agent
comprises at least one agent selected from the group
consisting of gadolinium, cerium, samarium, terbium, erbium,
lutetium, scandium, barium, bismuth, dysprosium, europium,
hafnium, indium, lanthanum, neodymium, niobium,
praseodymium, strontium, tantalum, ytterbium, yttrium, and
zirconium.

Cited References

Simpson et al. U.S. 2002/0090725 A1 July 11, 2002
(hereinafter “Simpson”)
Shastri et al. U.S. 6,471,993 B1 Oct. 29, 2002
(hereinafter “Shastri”)
Uvdal et al. U.S. 2008/0003184 A1 Jan. 3, 2008
(hereinafter “Uvdal”)

Grounds of Rejection
Claims 1, 3–8, 10, 17, 18, and 22 are rejected under 35 U.S.C.
§ 103(a) as being unpatentable over the combination of Simpson and Shastri.
Claims 1, 3–8, 10, 17–20, and 22 are rejected under 35 U.S.C.
§ 103(a) as being unpatentable over the combination of Simpson, Shastri,
and Uvdal.

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Application 11/083,602

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PRINCIPLES OF LAW
In making our determination, we apply the preponderance of the
evidence standard. See, e.g., Ethicon, Inc. v. Quigg, 849 F.2d 1422, 1427
(Fed. Cir. 1988) (explaining the general evidentiary standard for proceedings
before the Office). The Board “determines the scope of claims in patent
applications not solely on the basis of the claim language, but upon giving
claims their broadest reasonable construction ‘in light of the specification as
it would be interpreted by one of ordinary skill in the art.’” Phillips v. AWH
Corp., 415 F.3d 1303, 1316 (Fed. Cir. 2005) (quoting In re Am. Acad. of Sci.
Tech. Ctr., 367 F.3d 1359, 1364 (Fed. Cir. 2004).
“In rejecting claims under 35 U.S.C. § 103, the examiner bears the
initial burden of presenting a prima facie case of obviousness. Only if that
burden is met, does the burden of coming forward with evidence or
argument shift to the applicant.” In re Rijckaert, 9 F.3d 1531, 1532 (Fed.
Cir. 1993) (citations omitted). In order to determine whether a prima facie
case of obviousness has been established, we consider the factors set forth in
Graham v. John Deere Co., 383 U.S. 1, 17 (1966): (1) the scope and content
of the prior art; (2) the differences between the prior art and the claims at
issue; (3) the level of ordinary skill in the relevant art; and (4) objective
evidence of nonobviousness, if present.
“The combination of familiar elements according to known methods
is likely to be obvious when it does no more than yield predictable results.”
KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007).
ISSUE
The issue is: Does the cited prior art support the Examiner’s
conclusion that the claimed subject matter would have been obvious?
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FINDINGS OF FACT
The Examiner’s findings of fact are set forth in the Answer at pages
5–10. The following facts are highlighted.
1. Shastri discloses matrices that include a macrostructure having a
semi-solid network and voids, and a microstructure having voids,
in which the microstructure is located within the semisolid network
(abstract). The porous matrices are useful as scaffolds in tissue
engineering, such as providing alternatives to prosthetic materials
currently used in plastic and reconstructive surgery and in joint
repair and replacement, in formation of organ equivalents, etc.
(column 1, lines 19–65), and including vascular grafts (col. 17, l.
7). (Ans. 7.)
2. Shastri teaches various cells can be seeded or adsorbed onto the
porous matrices to form artificial organs (column 21, lines 30–44),
where the matrix materials “include PLA, PLGA, collagen, etc.”
(column 3, lines 41–62 and Table 1). (Ans. 7.)
3. The Shastri
matrices can also be used to deliver contrast agents to
specific sites, such as imaging by MRI. Examples of
suitable materials for use as contrast agents in MRI
include gadolinium chelates DTPA and gadopentotate . . .
The contrast or diagnostic agents can be detected using
standard techniques (column 22, lines 43+). Multilayered
matrices are also disclosed (column 25, lines 40+).
(Ans. 7–8.)
4. Shastri discloses that “[m]atrices that degrade at the same rate that
tissue ingrows into the matrix, or that tissue remodeling occurs
within the matrix, can be prepared.” (Col. 20, ll. 55–57.)
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5. Simpson teaches the formation and use of electroprocessed and
electrospun collagen, “including use as an extracellular matrix, and
together with cells, its use in forming engineered tissue. The
engineered tissue can include the synthetic manufacture of specific
organs and tissues which may be implanted into a recipient
(abstract).” (Ans. 5.)
6. In Simpson, “[s]ubstances can be deposited within, or anchored to
or placed on matrices. Cells are substances which can be deposited
within or on matrices (paragraph 0065).” (Ans. 5.)
7. Simpson discloses that
Electroprocessed collagen materials, such as matrices,
are useful in formation of prostheses. One application of
the electroprocessed matrices is in the formation of medium
and small diameter vascular prostheses. Some preferred
materials for this embodiment are collagen and elastin,
especially collagen type I and collagen type III. Some
examples include, but are not limited to coronary vessels for
bypass or graft, femoral artery, popliteal artery, brachial
artery, tibial artery, radial artery, arterial bifurcation, or
corresponding veins.
(Page 22 ¶ 193.)
8. Uvdal teaches that due to their magnetic properties, chelates of
gadolinium are commonly used as contrast agents in clinical MRI.
(Abstract ¶ 4.)

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Rejection 1
ANALYSIS
Appellants contend that the claimed “combination allows for the
monitoring of the body's remodeling and assimilation of a vascular
construct. (See page 2, lines 1-3 of the Application),” and that the cited
references to not address this problem in the art. (Br. 6.) Appellants further
argue that
there is no teaching or suggestion in Simpson that such
electrically or magnetically active materials can be used for
imaging or that they are in a concentration sufficient for
imaging of the matrix. Simpson makes no mention of using
such materials for imaging and, to the contrary, Simpson
describes an entirely different use for electrically or
magnetically active materials – controlled release of drugs.

(Br. 8.)
Appellants argue that, “[t]he examiner has failed to articulate any
rationale that would lead one skilled in the art to incorporate MRI imaging
agents into an electroprocessed matrix based on Simpson’s use of
magnetically or electrical sensitive materials for drug release.” (Br. 8.)
(emphasis added.) Appellants also argue that the Examiner has not
established, “an articulated reasoning with some rational underpinning of
why someone of ordinary skill in the art would have discerned from
Simpson that there was a need for monitoring tissue remodeling.” (Br. 9.)
Appellants argue that, “[t]he Examiner has offered no reason why one of
ordinary skill in the art would look to MRI contrast agents for imaging when
Simpson teaches instead the use of genetically engineered fluorescent cells.”
(Br. 10.)
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We are not persuaded by Appellants’ arguments. While we rely on
the evidence of record cited by the Examiner, we apply the cited references
in the opposite order such that our rationale differs somewhat from the
Examiner’s. Accordingly, we affirm the rejection of claims 1, 3–8, 10, 17,
18, and 22 as obvious over the combination of Simpson and Shastri but
designate our affirmance as a new ground of rejection.
Shastri discloses a three-dimensional collagen structure, such as a
vascular construct, having pores to permit cell attachment. (FF1, 2.) The
matrix of Shastri’s construct may further comprise an MRI image enhancing
agent such as gadolinium. (FF3.) Shastri discloses the preparation of
“[m]atrices that degrade at the same rate that tissue ingrows into the matrix,
or that tissue remodeling occurs within the matrix.” (FF4.) Shastri does not
specifically disclose that the MRI image enhancing agent is embedded
within the electrospun matrix or that the three-dimensional structure is
electrospun. Simpson, however, discloses that it is well known in the art to
use electrospun collagen for the formation of tissues including vascular
grafts. (FF7.) Simpson further discloses that it is well known that
“[s]ubstances can be deposited within, or anchored to or placed on matrices.
Cells are substances which can be deposited within or on matrices.” (FF6.)
We conclude that it would have been obvious to one of ordinary skill
in the art to use Simpson’s electrospun collagen matrix as a vascular graft
with a substance deposited therein in place of Shastri’s three-dimensional
collagen structure which may be used for tissue remodeling and vascular
grafts comprising an MRI imaging agent such as gadolinium, as both the
electrospun collagen matrix of Simpson and the three-dimensional structure
of Shastri are useful for construction of vascular grafts.
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Rejection 2
Claims 1, 3–8, 10, 17–20, and 22 are similarly rejected under
35 U.S.C. § 103(a) as being unpatentable over the combination of Shastri,
Simpson, and Uvdal.
Appellants contend that, “[t]he addition of Uvdal does not cure the
deficiencies of Simpson and Shastri.” (Br. 12.) Appellants further argue
that Uvdal is non-analogous art as it is directed to injectable compositions or
reagents for cell tracking (Br. 13) and that “[s]ince a person of ordinarily
[sic] skill, upon reading Simpson and Shastri, would not have been directed
to specifically using MRI contrast agents in a vascular construct, such a
person would have had no reason to combine Simpson and/or Shastri with a
teaching of a purportedly improved contrast agent from Uvdal.” (id.)
The Examiner finds that Uvdal teaches that due to their magnetic
properties, chelates of gadolinium are commonly used as contrast agents in
clinical MRI. (Ans. 9.) We agree with the Examiner for the reasons of
record, that
It would have been obvious to one of ordinary skill in the
art at the time of the invention to substitute gadolinium oxide
nanoparticles for Gd-DTPA MRI contrast agent in a collagen
matrix for tissue engineering. One would have been motivated
to do so because Shastri teaches that it is desirable to
incorporate MRI contrast agents such as Gd-DTPA in
polymeric matrix used for tissue engineering and artificial
organ constructs and because Uvdal teaches that gadolinium
oxide nanoparticles are superior to gadolinium chelates because
of higher relaxivity. One would have had a reasonable
expectation of success in doing so because Shastri teaches
methods of inclusion of such diagnostic agents within the
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matrices, and also teaches that imaging can be performed via
standard techniques (column 22-24).

(Ans. 9–10.) Since Uvdal discloses that its contrast agents have utility in
MRI and associated techniques (abstract), we find Uvdal to be analogous art
to the MRI agents used in Shastri. Having found no deficiency in the
combination of Simpson and Shastri, Rejection 2 is affirmed. Because our
rejection relies, in part, on the reasoning set forth with respect to Rejection
1, we designate our affirmance a new ground of rejection under 37 C.F.R. §
41.50(b).

CONCLUSION OF LAW
The cited references support the Examiner’s obviousness rejections,
however, because our rationale differs from that of the Examiner, we
designate the affirmances as new grounds of rejection over Shastri in view
of Simpson, or over Shastri in view of Simpson and Uvdal.

TIME PERIOD FOR RESPONSE
This decision contains new grounds of rejection pursuant to 37 C.F.R.
§ 41.50(b). 37 C.F.R. § 41.50(b) provides “[a] new ground of rejection
pursuant to this paragraph shall not be considered final for judicial review.”
37 C.F.R. § 41.50(b) also provides that the Appellants, WITHIN
TWO MONTHS FROM THE DATE OF THE DECISION, must exercise
one of the following two options with respect to the new ground of rejection
to avoid termination of the appeal as to the rejected claims:
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(1) Reopen prosecution. Submit an appropriate amendment of the
claims so rejected or new evidence relating to the claims so rejected, or both,
and have the matter reconsidered by the examiner, in which event the
proceeding will be remanded to the examiner. . . .
(2) Request rehearing. Request that the proceeding be reheard under
§ 41.52 by the Board upon the same record. . . .
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)(iv).

NEW GROUNDS under § 41.50(b)

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