Ex Parte Sparer et al

Board of Patent Appeals and Interferences

Apr 19, 2012

10640853 (B.P.A.I. Apr. 19, 2012)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte RANDALL V. SPARER, CHRISTOPHER M. HOBOT,
SUPING LYU, and KISHORE UDIPI
__________

Appeal 2011-008263
Application 10/640,853
Technology Center 1600
__________

Before LORA M. GREEN, JEFFREY N. FREDMAN, and
STEPHEN WALSH, Administrative Patent Judges.

WALSH, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) from the rejection of
claims directed to a method of tuning the delivery of an active agent from an
implantable medical device to a subject at a target diffusivity. The Patent
Examiner rejected the claims as anticipated and obvious. We have
jurisdiction under 35 U.S.C. § 6(b). We affirm.
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Application 10/640,853

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STATEMENT OF THE CASE
According to the Specification, “[a] polymeric coating on a medical
device may serve as a repository for delivery of an active agent (e.g., a
therapeutic agent) to a subject.” (Spec. 1, ll. 14-16.) “The present invention
provides active agent delivery systems that have generally good versatility
and tunability in controlling the delivery of active agents.” (Id. at 1, ll. 31-
33.)
Claims 89, 91-104, 134-138, and 140-150 are on appeal. Claim 89 is
illustrative, and it defines a method comprising (i) receiving an implantable
medical device that comprises “an active agent delivery system,” and
(ii) contacting the device with a bodily fluid, organ, or tissue of a subject to
deliver the active agent over a period of time, the delivery not controlled by
porosity. In claim 89, the active agent delivery system is defined as “formed
by a method comprising:”
receiving a hydrophobic active agent having a molecular weight of no
greater than about 1200 g/mol;
receiving a first polymer;
receiving a second polymer selected to be miscible with the first
polymer to form a miscible polymer blend that controls the delivery of the
active agent;
wherein at least one polymer has an active agent diffusivity
higher than the target diffusivity and at least one polymer has an
active agent diffusivity lower than the target diffusivity;
wherein each of the first polymer and the second miscible
polymer has at least one solubility parameter, and the difference
between at least one solubility parameter of each of the polymers is no
greater than about 3 J1/2/cm3/2;
wherein the active agent has a solubility parameter and the
difference between the solubility parameter of the active agent and at
least one solubility parameter of at least one of the polymers is no
greater than about 3 J1/2/cm3/2;
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and further wherein each of the solubility parameters is
independently determined by at least one method selected from measuring,
obtaining the solubility parameter from a reference publication, taking an
average of calculations performed using the Hoy Method and the Hoftyzer-
van Krevelen Method, and calculating by computer simulation; and
combining the first and second polymers in amounts sufficient to form
a miscible polymer blend that controls the delivery of the active agent over a
period of time;
wherein:
the swellability of the miscible polymer blend is no
greater than 10% by volume; and
the molar average solubility parameter of the miscible
polymer blend is no greater than 25 J1/2/cm3/2;
and further wherein:
the miscible polymer blend comprises at least one
hydrophobic cellulose derivative and at least one miscible
polyvinyl homopolymer or copolymer selected from the group
consisting of a polyvinyl alkylate homopolymer or copolymer,
a polyvinyl alkyl ether homopolymer or copolymer, a polyvinyl
acetal homopolymer or copolymer, and combinations thereof;
or
the miscible polymer blend comprises a polyurethane and
a second miscible polymer that is not a hydrophobic cellulose
ester; wherein the second miscible polymer is selected from the
group consisting of a polycarbonate, a polysulfone, a
polyurethane, a polyphenylene oxide, a polyimide, a polyamide,
a polyester, a polyether, a polyketone, a polyepoxide, a styrene-
acrylonitrile copolymer, a poly(vinyl ester), a poly(vinyl ether),
a polyacrylate, a poly(methyl acrylate), a polymethacrylate, a
poly(methyl methacrylate), and combinations thereof; or
the miscible polymer blend comprises a poly(ethylene-
co-(meth)acrylate) and a second miscible polymer not including
poly(ethylenevinyl acetate); wherein the second miscible
polymer is selected from the group consisting of a poly(vinyl
alkylate) homopolymer or copolymer, a poly(vinyl alkyl ether)
homopolymer or copolymer, a poly(vinyl acetal) homopolymer
or copolymer, a poly(alkyl and/or aryl methacrylate)
homopolymer or copolymer, a poly(alkyl and/or aryl acrylate)
homopolymer or copolymer, and combinations thereof; . . . .
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Appellants seek review1 of these rejections (App. Br. 7-8):
A. Claims 89, 91, 93-104, 134-138, 140-141, and 143-150 under 35 U.S.C.
§ 102(e) as anticipated by Sirhan.2
B. Claims 89, 91, 93-104, 134-138, 140-141, and 143-150 under 35 U.S.C.
§ 102(b) as anticipated by Hossainy.3
C. Claims 89, 91, 93-104, 134-138, 140-141, and 143-150 under 35 U.S.C.
§ 102(b) as anticipated by Whitbourne.4
D. Claims 89, 91-97, 99, 101-103, 134-138, 140-143, 145, and 147-150
under 35 U.S.C. § 102(e) as anticipated by Atala.5
E. Claims 89, 91-97, 99, 101-103, 134-138, 140-143, 145, and 147-150
under 35 U.S.C. § 103(a) as unpatentable over Sirhan and Van Krevelen.6
F. Claims 89, 91-97, 99, 101-103, 134-138, 140-143, 145, and 147-150
under 35 U.S.C. § 103(a) as unpatentable over Sirhan and Coleman.7

1 Appellants have directed the Board’s attention to U.S. Patent Application
Serial Nos. 10/640,713, 10/640,823, 10/916,162, 10/640,714, 10/640,702,
and 10/916,159. (App. Br. 2.) According to Appellants, “these applications
are not technically related to the present application, [but] Appellants wish
to bring the appeals in each case to the Board's attention as potentially
bearing on the Board's decision in the pending appeal.” (Id.) Appeals in the
first three listed applications were decided in December, 2011. See Appeals
No. 2011-004734, 2011-004751, and 2011-005172. Appeals in the next two
applications are being decided concurrently with this appeal. See Appeals
No. 2011-008373 and 2011-008372. According to USPTO records,
Application No. 10/916,159 is still in prosecution.
2 Motasim Sirhan et al., US 2002/0082679 A1, published June 27, 2002.
3 Syed F.A. Hossainy et al., US 6,153,252, issued Nov. 28, 2000.
4 Richard J. Whitbourne et al., US 6,110,483, issued Aug. 29, 2000.
5 Anthony Atala, US 6,576,019 B1, issued June 10, 2003.
6 D.W. Van Krevelen, Cohesive Properties and Solubility, PROPERTIES OF
POLYMERS 189-225 (1990).
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G. Claims 89, 91, 93-104, 134-138, 140, 141, and 143-150 under 35 U.S.C.
§ 103(a) as unpatentable over Hossainy and Van Krevelen.
H. Claims 89, 91, 93-104, 134-138, 140, 141, and 143-150 under 35 U.S.C.
§ 103(a) as unpatentable over Hossainy and Coleman.
I. Claims 89, 91, 93-104, 134-138, 140, 141, and 143-150 under 35 U.S.C.
§ 103(a) as unpatentable over Whitbourne and Van Krevelen.
J. Claims 89, 91, 93-104, 134-138, 140, 141, and 143-150 under 35 U.S.C.
§ 103(a) as unpatentable over Whitbourne and Coleman.
K. Claims 89, 91, 93-104, 134-138, 140, 141, and 143-150 under 35 U.S.C.
§ 103(a) as unpatentable over Atala and Van Krevelen.
L. Claims 89, 91, 93-104, 134-138, 140, 141, and 143-150 under 35 U.S.C.
§ 103(a) as unpatentable over Atala and Coleman.

ANTICIPATION
The Examiner’s position is that each of Sirhan, Hossainy,
Whitbourne, and Atala described the same method Appellants claim. Each
reference disclosed polymers that could be used in the form of a polymer
blend on an implantable medical device to deliver an active agent. The
Examiner found that none of the references disclosed blending polymers
with solubility parameter differences no greater than about 3 J1/2/cm3/2, but
the Examiner found that each reference “teaches the mixtures of the same
polymers and active ingredients as applicants claimed invention, therefore it
is inherent that the same polymers and actives will have the same solubility
parameters.” (E.g., Ans. 4.)

7 Michael M. Coleman et al., SPECIFIC INTERACTIONS AND THE MISCIBILITY
OF POLYMER BLENDS 49-125 (1991).
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Appellants contend that although each reference may teach some of
the same classes of polymers from which the first and second polymer may
be selected, each “fail[s] to teach the specific individual polymers from
among the classes listed that one should select so that the second polymer
will be miscible with the first polymer and possess the recited difference in
solubility parameter with respect to the first polymer,” and each “fail[s] to
teach, expressly or inherently, the relationship between the active agent and
the polymers of the miscible polymer blend as recited in each of Appellants'
independent claims.” (E.g., App. Br. 11.)
The issue with respect to each of the four anticipation rejections is the
same: whether the reference described Appellants’ method, including all the
limitations arranged as claimed.
We agree with Appellants that the principle to be applied to the issue
is:
unless a prior art reference discloses within the four corners of the
document not only all of the limitations claimed but also all of the
limitations arranged or combined in the same way as recited in the
claim, it cannot be said to prove prior invention of the thing claimed
and, thus, cannot anticipate under 35 U.S.C. § 102. . . . Thus, it is not
enough that the prior art reference . . . includes multiple, distinct
teachings that the artisan might somehow combine to achieve the
claimed invention.

Net MoneyIN, Inc. v. VeriSign, Inc., 545 F.3d 1359, 1371 (Fed. Cir. 2008).
We also note that “[i]nherency . . . 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.” MEHL/Biophile Int'l. Corp. v.
Milgraum, 192 F.3d 1362, 1365 (Fed. Cir. 1999), quoting In re Oelrich,
666 F.2d 578, 581 (CCPA 1981).
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On this record, we find the evidence insufficient to establish that any
of Sirhan, Hossainy, Whitbourne, or Atala necessarily described Appellants’
method in which solubility parameter differences between blended polymers
is no greater than about 3 J1/2/cm3/2. The anticipation rejections (listed as A-
D above) are therefore reversed.

OBVIOUSNESS
I. The rejections over Sirhan, Hossainy, Whitbourne, and Atala, each
combined separately with Van Krevelen (rejections E, G, I, and K).

The four rejections are substantially similar. In each, the Examiner
relied on findings made in the respective anticipation rejections. In those
rejections, the Examiner had found that each reference described methods of
delivering an active agent via an implantable device comprising a blended
polymer (Sirhan, Hossainy, and Whitbourne) or via an implantable device
comprised of the polymer blend (Atala). Each of Sirhan, Hossainy,
Whitbourne, and Atala was “silent” regarding the solubility parameter
values of the polymers to be blended and of the active agent. (E.g., Ans. 8.)
According to the Examiner, Van Krevelen showed it was well known that
“two substances with similar solubility properties should be mutually
soluble whereas when the difference between the solubility parameters
increases the tendency towards dissolution decreases.” (Id., citing Van
Krevelen at 201 lines 1-15.) Using δ to represent solubility parameter, Van
Krevelen stated:
ΔHM = 0 [the enthalpy of mixing equals zero] if δ1 = δ2, so that two
substances with equal solubility parameters should be mutually
soluble due to the negative entropy factor. This is in accordance with
the general rule that chemical and structural similarity favours
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solubility. As the difference between δ1 and δ2 increases, the tendency
toward dissolution decreases.
We may conclude that as a requirement for the solubility of a
polymer P in a solvent S, the quantity (δP – δS)2 has to be small, as
small as possible.
(Van Krevelen 201.) Van Krevelen also disclosed a Table listing
experimental and calculated values of solubility parameters for some
polymers. (Id. at 202.) The Examiner found that Van Krevelen would have
motivated one of ordinary skill in the art “to find the solubility parameters of
the polymers found within Atala in order to calculate which polymers are
likely to form blends when mixed together.” (Ans. 9.) The Examiner also
found that “[s]ince Atala discloses the use of polymer blends but does not
describe any method for predicting which polymers would be miscible with
each other one of ordinary skill in the art could have used solubility
parameters in a table as disclosed within van Krevelen and had a reasonable
expectation of success in blending two polymers if their solubility
parameters were relatively close.” (Id.) The reasoning in the other
rejections was the same.
Appellants’ contentions mirror the similarity of the rejections.
Concerning the combination of Sirhan and Van Krevelen, for example,
Appellants contend that “while the cited combination of documents
describes classes of polymers that encompass at least some of the polymers
from which polymers used to form the miscible polymer blends in
Appellants' claims may be selected, they neither teach nor suggest the
selection criteria for the recited combinations of polymers and active
agents.” (App. Br. 22.) According to Appellants, “[t]he subsets of polymer
and active agent combinations to which Appellants' claims are drawn is
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small and specific [but] the cited combination of documents provide no
teaching or suggestion that would direct one skilled in the art to Appellants'
claimed subset of polymer and active agent combinations from among the
innumerable combinations described.” (Id. at 23.)
However, we agree with the Examiner’s findings that Van Krevelen’s
explicit teaching to select for differences “as small as possible” provided
both motivation and guidance to select from Sirhan polymers and active
agents with solubility parameter differences “as small as possible.” It
appears reasonable to conclude that Van Krevelen’s “as small as possible”
included differences no greater than about 3 J1/2/cm3/2, and Appellants do not
argue otherwise. Because Van Krevelen did provide guidance to select
polymers and active agents with solubility parameter differences as small as
possible, we conclude that rejections E, G, I, and K established prima facie
cases for obviousness.
Appellants argue their position is supported by In re Baird, 16 F.3d
380 (Fed. Cir. 1994), Ortho-McNeil Pharmaceutical, Inc. v. Mylan Labs.
Inc., 520 F.3d 1358 (Fed. Cir. 2008), and Sud-Chemie, Inc. v. Multisorb
Technologies, Inc., 554 F.3d 1001 (Fed. Cir. 2009). (E.g., App. Br. 23-24.)
The fact that distinguishes this appeal from those cases is that in this appeal,
the record includes evidence that solubility parameter difference was known
in the art as a result effective variable for selecting miscible polymers and
compounds including active agents.
Claims 73-121 have not been argued separately and therefore fall with
claim 72. 37 C.F.R. § 41.37(c)(1)(vii).

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II. The rejections over Sirhan, Hossainy, Whitbourne, and Atala, each
combined separately with Coleman (rejections F, H, J, and L).

The four rejections are substantially similar. In each, the Examiner
relied on findings made in the respective anticipation rejections and found
that each of Sirhan, Hossainy, Whitbourne, and Atala was “silent” regarding
the solubility parameter values of the polymers to be blended and of the
active agent. (E.g., Ans. 9.) According to the Examiner, Coleman
“basically states that the closer two polymers are in their solubility
parameter the greater the likelihood that they will be miscible with each
other. In fact Coleman discusses a computer program one can use that
predicts the solubility parameters of two polymers and can predict, with
some degree of accuracy whether the polymers would be miscible.” (E.g.,
id. at 9-10.) The Examiner found Coleman “too thorough” to cite detailed
teachings, but concluded that “one of ordinary skill in the art could have
used solubility parameters or a program as disclosed within Coleman and
had a reasonable expectation of success in blending two polymers if their
solubility parameters were relatively close, especially if the program
predicted the polymer would be miscible.” (E.g., id.)
“Rejections on obviousness 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.” In re Kahn, 441 F.3d 977, 988 (Fed. Cir. 2006), cited with
approval in KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 417-18 (2007).
Rejections F, H, J, and L are too cursory to pass the Kahn test, and they are
therefore reversed.

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SUMMARY
We reverse the rejection of claims 89, 91, 93-104, 134-138, 140-141,
and 143-150 under 35 U.S.C. § 102(e) as anticipated by Sirhan.
We reverse the rejection of claims 89, 91, 93-104, 134-138, 140-141,
and 143-150 under 35 U.S.C. § 102(b) as anticipated by Hossainy.
We reverse the rejection of claims 89, 91, 93-104, 134-138, 140-141,
and 143-150 under 35 U.S.C. § 102(b) as anticipated by Whitbourne.
We reverse the rejection of claims 89, 91-97, 99, 101-103, 134-138,
140-143, 145, and 147-150 under 35 U.S.C. § 102(e) as anticipated by Atala.
We affirm the rejection of claims 89, 91, 93-104, 134-138, 140, 141,
and 143-150 under 35 U.S.C. § 103(a) as unpatentable over Sirhan and Van
Krevelen.
We reverse the rejection of claims 89, 91, 93-104, 134-138, 140, 141,
and 143-150 under 35 U.S.C. § 103(a) as unpatentable over Sirhan and
Coleman.
We affirm the rejection of claims 89, 91, 93-104, 134-138, 140, 141,
and 143-150 under 35 U.S.C. § 103(a) as unpatentable over Hossainy and
Van Krevelen.
We reverse the rejection of claims 89, 91, 93-104, 134-138, 140, 141,
and 143-150 under 35 U.S.C. § 103(a) as unpatentable over Hossainy and
Coleman.
We affirm the rejection of claims 89, 91, 93-104, 134-138, 140, 141,
and 143-150 under 35 U.S.C. § 103(a) as unpatentable over Whitbourne and
Van Krevelen.
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We reverse the rejection of claims 89, 91, 93-104, 134-138, 140, 141,
and 143-150 under 35 U.S.C. § 103(a) as unpatentable over Whitbourne and
Coleman.
We affirm the rejection of claims 89, 91-97, 99, 101-103, 134-138,
140-143, 145, and 147-150 under 35 U.S.C. § 103(a) as unpatentable over
Atala and Van Krevelen.
We reverse the rejection of claims 89, 91-97, 99, 101-103, 134-138,
140-143, 145, and 147-150 under 35 U.S.C. § 103(a) as unpatentable over
Atala and Coleman.

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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