Ex Parte Sun et al

Board of Patent Appeals and Interferences

Jan 20, 2012

10959780 (B.P.A.I. Jan. 20, 2012)

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.
10/959,780 10/06/2004 Wendell Sun STR.0310US 3372
84398 7590 01/23/2012
Finnegan/KCI
901 New York Avenue, NW
Washington, DC 20001
EXAMINER
SCHUBERG, LAURA J
ART UNIT PAPER NUMBER
1657
MAIL DATE DELIVERY MODE
01/23/2012 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 BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte WENDELL SUN, HERBERT DANIEL BENIKER,
and DAVID J. MCQUILLAN
__________

Appeal 2011-005384
Application 10/959,780
Technology Center 1600
__________

Before DONALD E. ADAMS, ERIC GRIMES, and JEFFREY N.
FREDMAN, Administrative Patent Judges.

GRIMES, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a
composition comprising an acellular tissue matrix. The Examiner has
rejected the claims as obvious. We have jurisdiction under 35 U.S.C. § 6(b).
We affirm.
STATEMENT OF THE CASE
The Specification discloses that tissue matrices are “used for the
repair of damaged tissues and organs” (Spec. 1: 6-7). The Specification
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discloses that “acellular tissue matrices (ATM) in which a substantial
proportion of water has been replaced with one or more water-replacing
agents can be stored for extended periods of time at ambient temperature
without substantial loss of structural or functional integrity” (id. at 1: 11-14).
The water-replacing agent may be glycerol, dimethylsulfoxide, or
polyhydroxyl compounds (id. at 1: 25-28).
Claims 1-6, 9-16, 18-22, and 94-97 are on appeal. Claim 1 is
representative and reads as follows:
1. A composition comprising:
an isolated acellular tissue matrix; and
within the acellular tissue matrix, a water-replacing reagent,
wherein the acellular tissue matrix contains not more than 30% of the
water that the matrix contains if fully hydrated, and
wherein the water-replacing reagent is present in an aqueous solvent
and the water-replacing reagent has a concentration of between about 60%
volume/volume and about 85% volume/volume in the aqueous solvent.

The claims stand rejected under 35 U.S.C. § 103(a) as follows:
• Claims 1-5, 10-12, 15, 16, 18, 20, 21, and 94 in view of Crouch;1
• Claims 6, 9, 13, 14, 19, and 22 in view of Crouch, Livesey2 and
Bronshtein;3 and
• Claims 95-97 in view of Crouch and Burgess.4

1 Crouch et al., Patent Application Publication US 2003/0135284 A1,
July 17, 2003
2 Livesey et al., Patent Application Publication US 2003/0143207 A1,
July 31, 2003
3 Bronshtein et al., US 6,872,357 B1, Mar. 29, 2005
4 Burgess et al., Patent Application Publication US 2003/0185702 A1,
Oct. 2, 2003
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Issue
The Examiner has rejected claims 1-5, 10-12, 15, 16, 18, 20, 21, and
94 under 35 U.S.C. § 103(a) as being obvious in view of Crouch. The
Examiner has also rejected claims 6, 9, 13, 14, 19, and 22 under 35 U.S.C.
§ 103(a) in view of Crouch, Bronshtein, and Livesey. Since Appellants have
waived any argument based on Bronshtein or Livesey (Appeal Br. 17-18),
we will consider the rejections together. In addition, the claims have not
been argued separately and therefore stand or fall together. 37 C.F.R.
§ 41.37(c)(1)(vii).
The Examiner finds that Crouch discloses “an invention wherein [a]
dehydrated bone or soft tissue graft, which contains less than 5% residual
moisture, is combined with a plasticizer composition that contains about
60% to 100%, but preferably 80% v/v of glycerol” (Answer 6). The
Examiner finds that Crouch discloses that “glycerol is combined with a
biocompatible solvent such as water” (id.). The Examiner finds that Crouch
discloses that the dehydrated bone or soft tissue graft is treated to remove
“bone marrow and/or cellular components … thus rendering them acellular
matrices” (id.). The Examiner concludes that “one of ordinary skill in the art
would have been motivated to include an aqueous solvent such as water in
the reference composition because Crouch et al suggest that water is a
suitable option as a solvent” (id. at 7).
Appellants contend that Crouch does not suggest the claimed amount
of water as a solvent for a plasticizer composition (Appeal Br. 13-17) and
one of skill in the art would not have had a reasonable expectation of success
in using water as a solvent in the plasticizer composition (Reply Br. 5).
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Appellants also contend that evidence of unexpected results has overcome
any prima facie case of obviousness (id. at 6).
The issues presented are: Does the evidence of record support the
Examiner’s conclusion that the acellular matrix composition of claim 1
would have been obvious in view of Crouch?
If so, have Appellants provided evidence of unexpected results that
outweighs the evidence supporting the prima facie case of obviousness?
Findings of Fact
1. Crouch discloses “a plasticized bone and/or soft tissue product that
exhibits materials properties that approximate those properties present in
normal hydrated tissue, is not brittle and does not necessitate rehydration
prior to implantation” (Crouch 3,¶ 0028).
2. Crouch discloses that “[p]lasticization … represents a method of
replacing free and loosely bound waters of hydration in the tissue with a
plasticizer composition containing one or more plasticizers” (id. at 4-5,
¶ 0055).
3. Crouch discloses that a plasticizer composition is “any
composition which includes one or more plasticizers and one or more
biocompatible solvents” (id. at 4, ¶ 0050).
4. Crouch discloses that “[s]uitable plasticizers include for example:
glycerol” (id. at 4, ¶ 0049) and “[s]uitable solvents include for example:
water” (id. at 4, ¶ 0050).
5. Crouch discloses that the “plasticizers are preferably employed at
concentrations in the range of from about 10% to 100% by weight or
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volume, preferably from about 50% v/v to about 100% v/v” (id. at 5,
¶ 0057).
6. Crouch discloses that the “plasticizer can be introduced into the
bone or soft tissue matrix at any number of steps in the processing
procedures and at a variety of concentrations with and/or without the use of
permeation enhancers” (id.).
7. Crouch discloses that, in one embodiment, “bone or soft tissue
grafts may[ ]be plasticized after cleaning and freeze-drying.… After removal
of bone marrow and/or cellular components, the tissue can be processed for
example by freeze-drying. Freeze-dried or dehydrated tissue grafts
preferably contain less than about 5% residual moisture.” (Id. at 6, ¶ 0065.)
8. Crouch discloses that the term soft tissue grafts includes
“connective tissue including ligaments and tendons, skin, vascular tissue
including arteries and veins, pericardium, dura mater, fascia, heart valves,
urethra, umbilical cord, and nerves” (id. at 4, ¶ 0053).
9. The Specification discloses that the acellular tissue matrices “can
include dermis[,] … fascia, pericardial tissue, dura, umbilical cord tissue,
placental tissue, cardiac valve tissue, ligament tissue, tendon tissue, arterial
tissue, venous tissue, neural connective tissue, urinary bladder tissue, ureter
tissue, or intestinal tissue” (Spec. 2: 4-9).
Principles of Law
“A prima facie case of obviousness typically exists when the ranges of
a claimed composition overlap the ranges disclosed in the prior art. . . .
Selecting a narrow range from within a somewhat broader range disclosed in
a prior art reference is no less obvious than identifying a range that simply
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overlaps a disclosed range.” In re Peterson, 315 F.3d 1325, 1329-30 (Fed.
Cir. 2003).
Analysis
Claim 1 is directed to a composition comprising an isolated acellular
tissue matrix that contains less than 30% of the water that the matrix
contains if fully hydrated and, within the acellular tissue matrix, a water-
replacing reagent that is present in an aqueous solvent and has a
concentration of 60% to 85% volume/volume in the aqueous solvent.
Crouch discloses a plasticization process for bone or soft tissue grafts
that replaces free and loosely bound waters of hydration in the tissue with a
plasticizer composition containing a plasticizer (e.g., glycerol) in a
biocompatible solvent (e.g., water), preferably in a concentration of about
50% to 100% v/v plasticizer. Crouch discloses that bone or soft tissue grafts
may be plasticized after cleaning to remove bone marrow and cellular
components, and freeze-drying to contain less than about 5% residual
moisture.
In view of the disclosure of Crouch, it would have been obvious to
one of ordinary skill in the art to plasticize a cleaned and dehydrated bone or
soft tissue graft with a water-based plasticizer and thereby arrive at the
acellular tissue matrix of claim 1 because Crouch expressly suggests the
benefits of plasticized bone and tissue grafts and also expressly suggests
water as a solvent for the plasticizer. The claimed concentration of water-
replacing agent in the aqueous solvent (60% to 85% v/v) is within the range
preferred by Crouch (50% to 100% v/v), and in accordance with In re
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Peterson, selecting a claimed narrower range from within a broader prior art
range is prima facie obvious.
Appellants argue that Crouch does not suggest a composition
comprising “a water replacing reagent ... wherein the water-replacing
reagent is present in an aqueous solvent,” as recited in claim 1, because
“Crouch, as a whole, is directed to ‘a plasticized dehydrated bone and/or
soft tissue.’” (Appeal Br. 13, citing Crouch at ¶ 0002). Appellants argue that
Crouch is directed to removal or replacement of free or loosely bound water
in tissue and therefore a skilled worker would not have been motivated to
use water as the solvent in its plasticizer composition (id.).
This argument is not persuasive. Crouch expressly discloses that a
plasticizer composition, comprising a solvent such as water, is used to
replace free and loosely bound waters of hydration in bone or soft tissue.
Thus, one of skill in the art would not interpret Crouch to exclude plasticizer
compositions that include water since Crouch expressly states that such
compositions could be used to obtain plasticized bone or tissue.
Appellants also argue that “the specific embodiments relied on by the
Examiner (e.g., paragraphs [0065]-[0066]) counsel against the use of water
as a solvent” (Appeal Br. 14) because these embodiments start with freeze-
dried tissue having less than about 5% residual moisture (id.) and use
isopropyl alcohol as a solvent (id. at 15). Similarly, Appellants argue that,
because “water is quite different from an alcoholic solution, a skilled artisan
would not have been able to predict … whether water would be as effective
as isopropyl alcohol in facilitating the penetration of glycerol.… That is,
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there is no reasonable expectation of success given the variability known in
the art.” (Reply Br. 5.)
This argument is not persuasive. Crouch expressly discloses that both
water and isopropyl alcohol are solvents that can be used to form the
plasticizing composition, and a finding of obviousness does not require the
replacement of isopropyl alcohol with water in any of Crouch’s specific
embodiments. Although Appellants point (Appeal Br. 15) to certain
advantages that Crouch discloses for using isopropyl alcohol in its
composition, including facilitating the penetration of glycerol, the discussion
relied on concerns using isopropyl alcohol as a permeation enhancer, not a
solvent, and Crouch discloses that its plasticizer composition can be
introduced into tissue with or without a permeation enhancer (see FF 6).
Appellants argue that “even if one were motivated to substitute water
for the compositions described in paragraphs [0064]-[0066], one would have
no reason to select the ranges as recited in the claims” (Appeal Br. 16).
This argument is not persuasive because the claimed range is within
the range recited in Crouch and therefore, in accordance with In re Peterson,
the claimed range would have been prima facie obvious based on Crouch.
The presumption of obviousness “will be rebutted if it can be shown: (1)
That the prior art taught away from the claimed invention … or (2) that there
are new and unexpected results relative to the prior art.” Iron Grip Barbell
Co. v. USA Sports, Inc., 392 F.3d 1317, 1322 (Fed. Cir. 2004). Appellants
have not shown that the prior art taught away or that the claimed range
provides unexpected results.
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Appellants also argue that “cancellous bone, which is the focus of
Crouch, has very little water compared to soft tissues like skin. Therefore,
even a relatively small amount of water in a bone storage composition will
result in bone that has more than 30% of the water that the matrix contains if
fully hydrated” (Appeal Br. 16).
This argument is not persuasive. Crouch is not limited to cancellous
bone, but also discloses plasticization of many of the same soft tissues as
described in the instant Specification (see FF 8, FF 9). Appellants have
provided no evidence to show that plasticizing these tissues, as suggested by
Crouch, would not result in an acellular tissue matrix having the water
content required by the claims.
Finally, Appellants argue that they have unexpectedly found that
reducing the water content by use of the claimed water replacing agent
“improve[s] stability and resistance to terminal sterilization with radiation”
(Reply Br. 6 (emphasis removed), citing Spec. 31-32). Appellants argue that
claim 1 therefore would not have been obvious because Crouch does not
address the problems solved by Appellants’ composition (id.).
These arguments are not persuasive. The burden of demonstrating
unexpected results rests on the party asserting them. In re Klosak, 455 F.2d
1077, 1080 (CCPA 1972). That burden has not been carried here because
Appellants have not pointed to any evidence in the record to establish that
the radiation resistance properties were unexpected. Notably, the
Specification states that “unrelated studies suggested that glycerol might
stabilize tissues against radiation damage” (Spec. 32: 1-2). Although the
Reply Brief asserts that the properties were unexpected, attorney argument is
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not evidence. In re Pearson, 494 F.2d 1399, 1405 (CCPA 1974).
Appellants’ argument Crouch does not recognize the problem Appellants
solved is not persuasive because, even in the absence of knowledge of any
radiation resistance effects, there was a reason to formulate the composition
of claim 1 because Crouch suggests such a formulation to achieve benefits
other than radiation resistance.
Conclusion of Law
The evidence of record supports the Examiner’s conclusion that the
acellular matrix composition of claim 1 would have been obvious in view of
Crouch. Appellants have not provided evidence of unexpected results that
outweighs the evidence supporting the prima facie case of obviousness.
II.
The Examiner has rejected claims 95-97 under 35 U.S.C. § 103(a) as
being obvious in view of Crouch and Burgess. Claims 96 and 97 have not
been argued separately and therefore stand or fall with claim 95. 37 C.F.R.
§ 41.37(c)(1)(vii)
Claim 95 depends from claim 1 and further requires that “the acellular
tissue matrix and water-replacing reagent have been exposed to γ, x or e-
beam radiation.”
The Examiner relies on Crouch as discussed above. The Examiner
finds that Burgess discloses “a method for sterilizing tissue to reduce the
level of one or more active biological contaminants or pathogens therein.…
The tissue includes processed tissue and acellular tissue for transplantation.”
(Answer 10.) The Examiner finds that Burgess discloses that “[r]adiation
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may be used for the sterilization such as e-beam, x- or γ-radiation” (id.).
The Examiner concludes that “one of ordinary skill in the art would have
been motivated to sterilize the composition of Crouch et al with the claimed
radiation types because Burgess et al teach that these types of radiation can
be used for sterilizing tissue such as acellular grafts to reduce the level of
one or more active biological contaminants or pathogens therein” (id.).
Appellants do not dispute that it would have been obvious, in view of
Burgess, to sterilize the bone or soft tissue products of Crouch with radiation,
but they argue that Burgess does not cure the deficiencies of Crouch in
suggesting the acellular tissue matrix of claim 1. This argument is not
persuasive for the reasons discussed above.
Appellants also argue that “nothing in either Burgess or Crouch would
have lead [sic] one of skill in the art to appreciate the advantages of the
specific ranges of water and water-replacing reagents for irradiat[ing] tissue
matrices” (Appeal Br. 18). Appellants argue that “having a specific level of
hydration within the tissue matrix, provides improved resistance to terminal
sterilization” (id. at 18-19).
This argument is not persuasive. As discussed above, the cited
references would have provided a reason to combine the limitations required
by claim 95 and Appellants have not provided any evidence that the
radiation resistance properties shown in the Specification are unexpected.
SUMMARY
We affirm the rejection of claims 1-6, 9-16, 18-22, and 94-97 under
35 U.S.C. § 103(a).
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TIME PERIOD FOR RESPONSE
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).

AFFIRMED

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