Ex Parte Binette et al

Board of Patent Appeals and Interferences

Sep 20, 2010

10374772 (B.P.A.I. Sep. 20, 2010)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte FRANCOIS BINETTE, JULIA HWANG,
SRIDEVI DHANARAJ, and ANNA GOSIEWSKA
__________

Appeal 2010-006136
Application 10/374,772
Technology Center 1600
__________

Before CAROL A. SPIEGEL, DONALD E. ADAMS, and STEPHEN
WALSH, Administrative Patent Judges.

WALSH, Administrative Patent Judge.

DECISION ON APPEAL1
This is an appeal under 35 U.S.C. § 134(a) from an obviousness
rejection of claims to a biocompatible tissue implant. We have jurisdiction
under 35 U.S.C. § 6(b). We affirm.

1 The two-month time period for filing an appeal or commencing a civil
action, as recited in 37 C.F.R. § 1.304, or for filing a request for rehearing,
as recited in 37 C.F.R. § 41.52, begins to run from the “MAIL DATE”
(paper delivery mode) or the “NOTIFICATION DATE” (electronic delivery
mode) shown on the PTOL-90A cover letter attached to this decision.
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STATEMENT OF THE CASE
Appellants seek review of the obviousness2 rejection of claims 98-
119. (App. Br. 2.) Claim 98 is illustrative and reads as follows:
98. A biocompatible tissue implant, comprising:
a first bioimplantable scaffold; and
tissue that has been processed under aseptic conditions to form a
plurality of tissue fragments said tissue fragments having viable cells,
said viable cells being capable of migrating out of the tissue
fragments;
wherein the tissue fragments have a size of about 0.1 mm3 to about
3 mm3 and are distributed on the surface of said first scaffold.

The Examiner rejected claims 98-119 under 35 U.S.C. § 103(a) as
unpatentable over Vyakarnam,3 Albrecht,4 Naughton,5 and Chvapil.6

OBVIOUSNESS
The Issue
The Examiner’s position is that each of the four cited prior art
references taught a biocompatible tissue implant comprising (i) cells seeded
and grown on the scaffold (Ans. 5, analyzing Vyakarnam’s disclosure); or
(ii) minced, very small cartilage tissue fragments including viable cells (id.

2 The claims were also rejected for nonstatutory obviousness-type double
patenting over claims in two issued patents and a copending application.
(Final Rej. 12.) Appellants acknowledge those rejections (App. Br. 1), but
do not appeal them (id. at 2).
3 US 6,534,084 B1, issued to Murty N. Vyakarnam et al., Mar. 18, 2003.
4 F. Albrecht et al., Closure of Osteochondral Lesions Using Chondral
Fragments and Fibrin Adhesive, 101 ARCH. ORTHOP. TRAUMA. SURG. 213-
217 (1983).
5 US 5,842,477, issued to Gail K. Naughton et al., Dec. 1, 1998.
6 US 5,078,744, issued to Milos Chvapil, Jan. 7, 1992.
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at 6, analyzing Albrecht’s disclosure); or (iii) periosteal/perichondrial tissue
fragments that can be sutured and closed in layers having cells/tissue
disposed within the scaffold (id. at 6-7, analyzing Naughton’s disclosure); or
(iv) cells injected into the scaffold material (id. at 7, analyzing Chvapil’s
disclosure). The Examiner found that a person of ordinary skill would have
been motivated to substitute Vyakarnam’s viable cells with tissue fragments
“because all of Albrecht et al, Naughton et al and Chvapil provide the
benefits (such as anchoring functions, acting as a source of viable cells such
as chondrocytes, stromal cells, growth factors, and immunological
compatibility . . . ) of using tissue fragments. (Id. at 7.) According to the
Examiner, the specific claim limitations concerning tissue fragment sizes
would have been obvious over the Naughton and Albrecht disclosures of
minced tissue. (Id. at 8-9.)
Appellants contend that “none of the cited references, whether taken
alone or in combination, teach or suggest tissue fragments distributed on the
surface of a scaffold.” (App. Br. 5.) According to Appellants’ assessment
of the prior art, Vyakarnam taught seeding the implant with cells, not tissue
fragments (id. at 6); “[n]either the ‘suspension of individual cells’ or
‘periostial/perichondrial tissue’ disclosed by Naughton are tissue fragments
distributed on the surface of a scaffold” (id.); Naughton taught placing a
single piece of tissue, not a plurality of tissue fragments, on the scaffold (id.
at 7); Chvapil taught cultured cells injected into a scaffold, not tissue
fragments distributed on a scaffold (id.); and Albrecht’s mixture of minced
cartilage with thrombin and fibrinogen precipitate “would, at best, result in
minced cartilage in an artificial fibrin matrix, not [tissue] fragments
distributed on the surface of a scaffold” (id. at 8).
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Appellants contend that the combined prior art teachings did not
suggest tissue fragments distributed on the surface of a scaffold (id.), nor did
the prior art suggest the claimed fragment size range (id. at 8-11), nor
recognize that fragment size range is a result effective variable (id. at 12-13).
The Declaration of Julia Hwang is said to show “that tissue fragments of the
entire claimed size range yielded unexpected results.” (Id. at 14-15.)
The issues are:
does the evidence support the Examiner’s finding that the prior art
suggested distributing tissue fragments on the surface of a scaffold;
does the evidence support the Examiner’s finding that the claimed
tissue fragment size range was suggested by the prior art;
does the preponderance of the evidence of record, including
Appellants’ evidence of unexpected results, weigh in favor of an ultimate
conclusion of obviousness?

Findings of Fact
1. We adopt the Examiner’s findings of fact.
2. Appellants rely on a “1.132 Declaration of Julia Hwang.” (App. Br.
14.)
3. The Declaration states: “[e]xperiments were performed to evaluate
the tissue size requirement for chondrocytes to migrate from minced
cartilage tissue into bioresorbable scaffolds.” (Decl. ¶6.)
4. The Declaration states: “when constructs were formed from 7mm3
tissue fragments and a scaffold were implanted on the back of SCID
mice, the implants did not exhibit an uniform fill with cartilaginous
tissue.” (Id. at ¶7.)
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5. The Declaration states: “[u]nexpectedly, only fragments 3mm3 and
smaller exhibited uniformly filled cartilaginous tissue.” (Id.)
6. The Declaration states: “fragments with a volume less than about
.004mm3 unexpectedly showed a reduction in the number of cells
migrating from the minced tissue and proliferating in the scaffold.”
(Id. at ¶9.)

Principles of Law
A rejection for obviousness must include “articulated reasoning with
some rational underpinning to support the legal conclusion.” KSR Int’l Co.
v. Teleflex Inc., 550 U.S. 398, 418 (2007), quoting In re Kahn, 441 F.3d 977,
988 (Fed. Cir. 2006). “The combination of familiar elements according to
known methods is likely to be obvious when it does no more than yield
predictable results.” KSR, 550 U.S. at 416. “After evidence or argument is
submitted by the applicant in response, patentability is determined on the
totality of the record, by a preponderance of evidence with due consideration
to persuasiveness of argument.” In re Oetiker, 977 F.2d 1443, 1445 (Fed.
Cir. 1992) (citations omitted).
[E]ven though applicant’s modification results in great
improvement and utility over the prior art, it may still not be
patentable if the modification was within the capabilities of one
skilled in the art, unless the claimed ranges “produce a new and
unexpected result which is different in kind and not merely
degree from the results of the prior art.”

In re Huang, 100 F.3d 135, 139 (Fed. Cir. 1996) (citations omitted).
“Establishing that one (or a small number of) species gives unexpected
results is inadequate proof, for it is the view of this court that objective
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evidence of non-obviousness must be commensurate in scope with the
claims which the evidence is offered to support.” In re Greenfield, 571 F.2d
1185, 1189 (CCPA 1978) (quotations omitted).

Analysis
A. Claim 98
We find the evidence supports the Examiner’s findings and
conclusion of obviousness. The Examiner made ample evidence of record
that a person of ordinary skill in the art at the time of the invention knew that
viable cells were capable of migrating out of tissue fragments. Similarly,
there is ample evidence in the record that it was well known to seed a
bioimplantable scaffold with such cells.
The Examiner articulated a reasonable basis for concluding that, based
on the known practice of using minced tissue fragments as the source of
cells for implantation, it would have been obvious to use the known minced
tissue fragments themselves as the direct source of cells in the implant.
Appellants’ Declaration evidence of unexpected results addresses cell output
by one kind of tissue, but the claims are not so limited, and include tissues of
any kind. See Greenfield, 571 F.2d at 1189. The Declaration does not
explain that similar results would be expected for tissue fragments in the
claimed size range, regardless of tissue type.
Claims 99, 103-105, 107-113, and 117-119 have not been argued
separately and therefore stand or fall with claim 98. 37 C.F.R.
§ 41.37(c)(1)(vii).
B. Claims 100-102
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Claim 100 depends from claim 99, which in turn depends from claim
98:
100. [The tissue implant of claim 98,
wherein the first bioimplantable scaffold comprises a biocompatible
polymer selected from the group consisting of a synthetic polymer, a
natural polymer, an injectable gel, a ceramic material, autogeneic
tissue, allogeneic tissue, xenogeneic tissue, and combinations thereof],
wherein the tissue implant has been incubated for a duration and
under conditions effective to allow cells within the tissue fragments to
populate the scaffold.

The Examiner found that Vyakarnum did not teach incubating the
implant under the conditions recited in claims 100-102. (Ans. 5.) However,
the Examiner found Chvapil’s teaching to seed a scaffold with cells and
cultivate the seeded scaffold before implantation was pertinent. (Id. at 7.)
The Examiner concluded that it would have been obvious to apply Chvapil’s
incubation period to Vyakarnum’s scaffold seeded with tissue fragments.
(Id. at 7-8.)
Appellants argue that “the cultured cells of Vyakarnam, Naughton,
and Chvapil are not equivalent to tissue fragments [and these references]
therefore provide no teaching or suggestion regarding an implant that has
been incubated to allow cells within tissue fragments to populate the
scaffold.” (App. Br. 17-18.)
Chvapil taught incubating small pieces of tendon to allow tenoblasts
to grow and migrate from the tendon fragments, harvesting the tenoblasts,
and injecting them into the scaffold (Chvapil, col. 5, ll. 36-42), and the
Examiner concluded it would instead have been obvious to allow tissue
fragments placed on a scaffold to incubate for a period of time while the
fragments produced cells. While we agree with Appellants that cells are not
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equivalent to fragments, Chvapil’s fragments produce cells during the
incubation period, cells which are then used to seed a scaffold. Given those
teachings, we cannot agree that the references provide “no” suggestion to
allow the tissue fragments to seed the scaffold before implantation, as
references teach that the cells proliferate in the scaffold after implantation.
Claims 101 and 102 have not been argued separately and therefore
stand or fall with claim 100. 37 C.F.R. § 41.37(c)(1)(vii).
C. Claims 106 and 114-116
Claim 106 reads:
106. The tissue implant of claim 98 further comprising a second
bioimplantable scaffold wherein the second bioimplantable scaffold is
disposed over a plurality of tissue fragment on the surface of the first
bioimplantable scaffold, such that at least a portion of the at least one
tissue fragment is disposed between at least two bioimplantable
scaffolds.

The Examiner found that an implant having at least one tissue
fragment disposed between two bioimplantable scaffolds would have been
obvious “as evident by the fact that Naughton et al teach the implantation of
the scaffold along with the tissue fragments in a defect site that can be
sutured and closed in various layers having cells/tissue disposed within the
scaffold (see Naughton et al, column 20, 2nd and 3rd paragraph, in
particular).” (Ans. 9.)
Appellants argue that “although Naughton discloses that
periosteal/perichondrial tissue ‘can be laid over or under the scaffold at the
implantation site,’ the periosteal/perichondrial tissue is not disposed over a
plurality of tissue fragments because none of the cited references, including
Naughton, teach or suggest tissue fragments disposed on the surface of a
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scaffold. Moreover, the periosteal/perichondrial tissue is not a second
bioimplantable scaffold . . . .” (App. Br. 19.)
The Examiner’s rejection is founded on the earlier conclusion that it
would have been obvious to substitute tissue fragments for the cells seeded
onto Vyakarnam’s scaffold. In light of that conclusion, we agree with the
Examiner that Naughton’s teaching to close the defect site with layers fairly
suggested the claimed implant comprising at least a tissue fragment between
at least two scaffolds.
Claims 114-116 have not been argued separately and therefore stand
or fall with claim 106. 37 C.F.R. § 41.37(c)(1)(vii).

CONCLUSIONS
The evidence supports the Examiner’s finding that the prior art
suggested distributing tissue fragments on the surface of a scaffold.
The evidence supports the Examiner’s finding that the claimed tissue
fragment size range was suggested by the prior art.
The preponderance of the evidence of record, including Appellants’
evidence of unexpected results, weighs in favor of an ultimate conclusion of
obviousness.

SUMMARY
We affirm the rejection of claims 98-119 under 35 U.S.C. § 103(a) as
unpatentable over Vyarkarnam, Albrecht, Naughton, and Chvapil.

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

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