Ex Parte Cheng et al

Patent Trial and Appeal Board

Nov 19, 2012

10921735 (P.T.A.B. Nov. 19, 2012)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte PEIWEN CHENG, PATRICE TREMBLE, WENDA CARLYLE,
DIANE JUDD, and KISHORE UDIPI
__________

Appeal 2011-012701
Application 10/921,735
Technology Center 3700
__________

Before LORA M. GREEN, JEFFREY N. FREDMAN, and
ULRIKE W. JENKS, Administrative Patent Judges.

JENKS, Administrative Patent Judge.

DECISION ON APPEAL
This is a decision on appeal under 35 U.S.C. § 134 involving claims
directed to a stent delivery system comprising stents with continuously
varying coatings. The Patent Examiner has rejected the claims as obvious.
We have jurisdiction under 35 U.S.C. § 6(b). We reverse.
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STATEMENT OF THE CASE
The invention is directed to an implantable stent. The “invention
provides a stent with a gradient coating in which at least one coating
component varies continuously with coating thickness.” (Spec. 3, ll. 23-25.)
The stent gradient coating has a “high concentration of a therapeutic agent at
the inner edge of the stent coating and a low concentration at the outer edge
of the stent coating.” (Spec. 3, ll. 29-31.)
Immediately after implantation, the coated stent delivers the
anti-inflammatory drug to treat the tissue trauma from
angioplasty and stent implantation. At a desired time, such as a
few days to a few weeks, most of the anti-inflammatory drug
will be gone and the coated stent delivers the anti-proliferative
drug to prevent restenosis and tissue growth on the stent. The
anti-proliferative drug delivery continues long term, such as a
number of months or years. The continuously varying coating
component concentration provides control over the timing and
dosage of the two drugs.

(Spec. 12, ll. 23-30.)

Claims 1, 2, 5-11, 14-18, and 44-65 are on appeal, and can be found in
the Claims Appendix of the Appeal Brief (App. Br. 27-34). Claims 1, 10,
54, 58, and 62 are independent claims. Claim 1 is representative of the
claims on appeal, and reads as follows (emphasis added):
1. A stent delivery system comprising:
a catheter;
a balloon operably attached to the catheter;
a stent disposed on the balloon; and
a continuous coating disposed on the stent, the continuous
coating having a thickness and comprising a first coating component
and a second coating component, the first coating component being
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selected from the group consisting of drugs, therapeutic agents,
polymers, co-polymers, bi-polymers, and combinations thereof;
wherein, before implantation in a lumen, concentration of the
first coating component varies continuously in a radial direction over
at least part of the thickness of the continuous coating, and
the concentration of the first coating component varies linearly
over at least part of the thickness of the continuous coating.

The following grounds of rejection are before us for review:
1. The Examiner has rejected claims 1, 2, 5-7, 9-11, 14-16, and 18
under 35 U.S.C. § 103(a) as unpatentable over Tuch1 in view of
Chandrasekaran.2
2. The Examiner has rejected claims 8 and 17 under 35 U.S.C.
§ 103(a) as unpatentable over Tuch in view of Chandrasekaran and
further in view of Harish.3
3. The Examiner has rejected claims 1, 2, 10, 11 and 44-65 under 35
U.S.C. § 103(a) as unpatentable over Schwarz4 in view of
Chandrasekaran and further in view of Harish.

ISSUES
The Examiner takes the position that “Tuch discloses varying the
concentration of the first coating component in a radial direction over at
least part of the thickness of the coating, Tuch fails to disclose that [the]
coating is varied linearly over said thickness.” (Ans. 4.) The Examiner

1 Tuch, US 5,824,048, issued Oct. 20, 1998.
2 Chandrasekaran et al., US 6,638,301 B1, issued Oct. 28, 2003.
3 Harish et al., US 2002/0122877 A1, published Sep. 5, 2002.
4 Schwarz et al., US 6,368,658 B1, issued Apr. 9, 2002.
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finds that “Schwarz discloses applying two coating components
simultaneously and varying the concentrations of coating components across
a thickness of the coating.” (Ans. 11.) The Examiner rejects the claims
based on the combination of either Tuch and Chandrasekaran, or Schwarz
and Chandrasekaran. The Examiner relies on Chandrasekaran for the
“teaching of linearly varying concentrations of coating components and its
explanation that such a concentration profile may be produced by
simultaneously applying both coating components and controlling the rates
at which each component is applied.” (Id. at 9.) The Examiner concludes
that it would have been obvious to one of ordinary skill in the art to modify
the apparatus of Tuch or to modify the procedure of applying coatings onto a
stent as disclosed by Schwarz because “Chandrasekaran teaches that it was
known to vary coating concentrations linearly and doing so would allow a
manufacturer to accurately control the release profile(s) of the active
agent(s).” (Id. 4, 7.)
Appellants contend that the combination of Tuch or Schwarz with
Chandrasekaran fails to disclose all the elements of the claimed inventions.
(App. Br. 13, 19.) Additionally, the combination would not be obvious
because the “methods of the Chandrasekaran patent require high
temperatures and/or ionization, making them unsuitable for drugs,
therapeutic agents, polymers, co-polymers, and bi-polymers as claimed”
(App. Br. 15 and 22; Reply Br. 5, 7).
The issues with these rejections are whether the Examiner has
presented a prima facie case of obviousness with respect to the combination
of Tuch and Chandrasekaran, or Schwarz and Chandrasekaran.
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FINDINGS OF FACT
FF1. The Specification provides that:
[T]he continuous coating [] can coat the whole stent [], both
inside and outside, and around the cross section of individual
stent elements. The continuous coating [] can be any coating
that can elute a therapeutic agent and maintain coverage of the
stent elements. The coating components, such as the
therapeutic agent or the polymer, vary continuously over the
thickness of the continuous coating [].

(Spec. 6, ll. 9-14)
FF2. The Specification provides that:
The concentration of the therapeutic agent in the polymer varies
continuously over the thickness of the continuous coating [].
Different profiles of the therapeutic agent can accomplish
different therapeutic results. For example, a high concentration
of therapeutic agent in the continuous coating [] near the stent
element [] with a low concentration in the continuous coating []
at the outer edge will suppress any burst release and provide a
steady long-term dose.

(Spec. 7, ll. 24-31)
FF3. Figure 4A, of the Specification, reproduced below shows a linear
concentration profile.
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12701
/921,735
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Application 10/921,735

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[T]he coating component concentration is a maximum at the
zero coating thickness at the stent element and declines to a
minimum at the coating thickness TO at the exterior of the
stent. Profile B is has a linear gradient, while profile A is
concave down and profile C is concave up. The three profiles
illustrate how a continuously varying coating component can be
tailored for a desired result.

(Spec. 11, l. 13 to 11, l. 18.)
FF5. Tuch disclosed a stent with a “polymer and a therapeutic substance on
the body of a stent, and in particular on its tissue-contacting surface, in
which the coating has a greater concentration of therapeutic substance on the
portion of the coating nearest the stent body than near the exterior surface of
the coating.” (Tuch, col. 2, ll. 37-42; Ans. 3.) “By placing the greater
concentration of the drug toward the stent body, control over the rate of
administration of the drug is significantly improved.” (Tuch, col. 2, ll. 46-
48; Ans. 4.)
FF6. Tuch disclosed “a higher drug-to-polymer ratio in the inner layers
than in the outer layers would result in a lower initial dose and a total dose
which would be delivered more evenly and over a much longer period of
time.” (Tuch, col. 3, ll. 19-23; Ans. 4.)
FF7. Tuch disclosed that when “both the drug and polymer are soluble in
the solvent, the drug and polymer are dissolved slightly in the application of
each of the coating overlayers which creates a concentration gradient of drug
in the overlayers that is sharply reduced from that in the main coating
nearest the stent body.” (Tuch, col. 3, ll. 29-34; Ans. 4.)
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12701
/921,735
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Application 10/921,735

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The release profile of the drug may also be altered by
concurrently applying several layers of gradient concentrations
to yield a multi-phasic release profile. For example, the ratio of
copolymers of polylactic acid ("PLA") and polyglycolic acid
("PGA") (Birmingham Polymers, Birmingham, Ala.) containing
0.1-10% of a peptide analog such as an analog of Somatostatin
may be varied sequentially so that the drug has multiple peak
release drug concentrations. . . . The release rate from each
layer is optionally different such that the final result is several
different peaks corresponding to the release from each
individual layer. Layers are not limited to a single drug.

(Schwarz, col. 14, ll. 41-55; Ans. 8.)
FF12. Schwarz further disclosed:
The invention includes parallel applications of drug(1)-
polymer(1)-solvent(1) and drug(2)-polymer(2)-solvent(2) to
eliminate compatibility or solubility issues- Examples include
the simultaneous application of (i) cisplatinhydroxypropyl
methyl cellulose-water and paclitaxel-PCL/PLA-chloroform
from two different feeds; (ii) albumin or gelatin solution from
one feed and gluraldehyde crosslinker from second feed; and
(iii) acrylate monomer solution from one feed and methylene
bis acrylamide as crosslinker for the second feed.

(Schwarz col. 15, ll. 19-28; Ans. 6.)

PRINCIPLES OF LAW
“The Patent Office has the initial duty of supplying the factual basis
for its rejection. It may not . . . resort to speculation, unfounded assumptions
or hindsight reconstruction to supply deficiencies” in the cited references. In
re Warner, 379 F.2d 1011, 1017 (CCPA 1967).
“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
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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).
“[R]ejections 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.” 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).

ANALYSIS
Ground 1: Obviousness over Tuch in view of Chandrasekaran
Based on the combination of Tuch and Chandrasekaran the Examiner
concludes, that at the time of the Appellants’ claimed invention it would
have been prima facie obvious to use the concept of linear deposition on a
stent as disclosed in Chandrasekaran and apply that to the polymer drug
stent depositions as disclosed in Tuch. (FFs 5-11; Ans. 3-4.)
Appellants contend that the combination of Tuch and Chandrasekaran
“fail to include each and every element of Appellants[’] invention as
claimed.” (App. Br. 13.) Appellants assert “that the Chandrasekaran patent
must be considered as a whole. The Chandrasekaran patent discloses a
radiopaque layer and a drug-releasing layer over the radiopaque layer, but
only discloses a compositional gradient of metallic materials in the
radiopaque layer.” (Reply Br. 6.)
Claim 1 requires in pertinent part the limitations of a “continuous
coating” disposed on the stent and that the component “varies linearly” over
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at least part of the thickness of the coating. The Specification provides that
in a continuous coating the “therapeutic agent in the polymer varies
continuously over the thickness” of the coating. (FFs 1-4.) The
Specification provides several variations of continuous coating profiles,
noticeable in all the examples is that there are no abrupt changes in the
component concentration over the coating thickness. (FF4.) Thus, the
limitation of a “continuous coating” disposed on the stent is interpreted to be
a smooth transition, without abrupt concentration changes or steps, in the
component concentration over the thickness of the coating layer, where the
concentration of the component can either increase or decrease from the
stent sidewall to the outer edge of the coating.
The limitation that the component “varies linearly” over at least part
of the thickness of the coating is interpreted to be a change in the component
concentration versus the thickness of the coating layer, thus, it is a
continuous coating with the additional requirement that the slope of the line
is straight (FFs 3-4). The concentration of the component can either increase
or decrease from the stent sidewall to the outer bound of the coating. (FFs 3-
4, Spec. 12, ll. 15-32, see also Figure 4C.)
We agree with the Appellants position that the Examiner has not set
out a prima facie case of obviousness. We find that the Examiner has not
adequately explained why the cited references would have prompted an
ordinary artisan to apply a therapeutic layer or a polymer layer in a linear
fashion onto a stent as claimed. The Examiner takes the position that
Chandrasekaran teaches a stent having two coating components that vary
linearly, and that the deposition of the materials is achieved by
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“simultaneously applying both coating components and controlling the rates
at which each component is applied.” (Ans. 4, 9.) The disclosure in
Chandrasekaran of a method of achieving linear coatings using ceramics and
metals does not address the reason why the ordinary artisan would seek to
make linear coatings of therapeutic drugs or polymers. Tuch already
recognized that placing the concentration of therapeutic agent close to the
stent surface is beneficial because it improves the administration of the drug
(FFs 5, 6, 8). Tuch achieves this drug elution profile by pre-eluting the drug
from the stent (FF8) or by applying an overlayer coat onto the stent (FF7).
As recognized by the Examiner “Tuch fails to disclose that coating is varied
linearly over said thickness.” (Ans. 4.) The Examiner has not, however,
explained or pointed to any evidence in Chandrasekaran or Tuch to explain
why an ordinary artisan would have looked to produce a linear gradient
deposition of a therapeutic or polymer on a stent in the first place.
The Examiner has not pointed to any evidence in Chandrasekaran or
Tuch that would lead the ordinary artisan to apply a therapeutic agent or
polymer in a linearly varying gradient across the thickness of the coating.
The Examiner relies on Chandrasekaran “for its teaching of linearly varying
concentrations of coating components and its explanation that such a
concentration profile may be produced by simultaneously applying both
coating components and controlling the rates at which each component is
applied.” (Id. at 9.) We find that Chandrasekaran disclosed a method to
make stents more visible on X-ray, so that they can be more easily
monitored once they are placed into position in the body. The problem
solved by Chandrasekaran was to take X-ray dense material that may not
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have the desired biocompatibility level and apply it in conjunction with a
biocompatible material. (Chandrasekaran, col. 4, ll. 44-61.) As
acknowledged by Appellants, Chandrasekaran disclosed adding therapeutic
agents to the stent, but these therapeutic agents are applied as an additional
layer on top of the radiopaque layer and not as a gradient. (Reply Br. 6.)
The Examiner finds that the “teaching of varying concentrations linearly is
applicable to the Tuch device since it would allow more continuous and
accurate control of the release profile of the active agent(s).” (Ans. 9.) The
Examiner has not provided any other rationale as to why an ordinary artisan
would have considered it obvious to apply the drugs in a linear fashion and
what benefits may be obtained in comparison to applying the drug coatings
as very thin layered coatings as a series of small steps (FF3). What is
missing from the Examiner's analysis is evidence that an artisan would have
a reason to produce linear coatings of therapeutic agents on a stent. See
KSR, 550 U.S at 418 (obviousness rejections require “some articulated
reasoning with some rational underpinning”).
We are not persuaded that the Examiner has made out a prima facie
case of obviousness as to claims 1 and 10. We therefore reverse the
Examiner's obviousness rejection of those claims over Tuch and
Chandrasekaran. We thus reverse the rejection of claims 1 and 10 under 35
U.S.C. § 103(a) as being obvious. As claims 2, 5-7, 9, 11, 14-16, and 18
have not been argued separately, they stand with claims 1 and 10 as
acknowledged by the Appellants (App. Br. 16). 37 C.F.R. § 41.37(c)(vii).
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Ground 2: Obviousness over Tuch, Chandrasekaran and Harish
Based on the combination of Tuch, Chandrasekaran and Harish, the
Examiner concludes, that at the time of the Appellants’ claimed invention it
would have been prima facie obvious to use the concept of linear deposition
on a stent as disclosed in Chandrasekaran and apply that to the polymer or
therapeutic agent depositions on a stent as disclosed in Tuch and Harish.
(FFs 5-11; Ans. 3-4.)
Appellants contend the “Tuch patent and the Chandrasekaran patent
and the Harish publication, alone or in combination, fail to disclose, teach,
or suggest each and every element of the Appellant's invention as claimed.”
(App. Br. 17.) “[T]he Harish publication only teaches a conventional
uniform coating, so there would be no reason for one skilled in the art to
combine the teachings of Harish publication with the teachings of the Tuch
patent and the Chandrasekaran patent.” (Id. at 18.) “The Appellant
respectfully points out that the Harish publication cautions that particular
care should be taken to ensure that the active ingredient employed in the
composition will not be adversely affected by the heat treatment applied to
the sheath formed from the composition as described below.” (Reply Br. 7.)
We agree with Appellants’ position. We are not persuaded that the
Examiner has adequately explained why the cited references would have
prompted an ordinary artisan to apply therapeutic agents or polymers in a
linear fashion onto a stent. For the reasons set out above we are not
persuaded that the combination of Tuch and Chandrasekaran would have
lead the ordinary artisan to produce linear therapeutic or polymer coatings
on a stent as claimed. The Examiner finds that “Tuch[’s] disclosure is
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compatible with a wide variety of coating components including therapeutic
agents and pharmaceutically active compounds. Anti-inflammatory agents
are considered to fall within these categories, and providing such an agent
would allow benefits such as reduced inflammation at the target site.” (Ans.
10.) However, what is missing from the Examiner's analysis is evidence that
an artisan would have a reason to produce a continuous or linear coating on
a stent in the first place. See KSR, 550 U.S at 418 (obviousness rejections
require “some articulated reasoning with some rational underpinning”).
The preponderance of evidence on this record fails to support
Examiner's finding that Tuch in view of Chandrasekaran teaches Appellants’
claimed invention. The rejection of claims 8 and 17 under 35 U.S.C. §
103(a) as being obvious over Tuch in view of Chandrasekaran and further in
view of Harish is reversed.

Ground 3: Obviousness over Schwarz, Chandrasekaran and of Harish
Based on the combination of Schwarz and Chandrasekaran, the
Examiner concludes that it would have been prima facie obvious at the time
of Appellants’ claimed invention to use the linear coating profiles on a stent
as taught by Chandrasekaran with the polymer-therapeutic agent
combination coatings as taught by Schwarz. (Ans. 6-7, 11.)
Appellants contend that “the Schwarz patent discloses a layered,
discontinuous coating, in contrast to the continuous coating as claimed. The
Schwarz patent also fails to disclose the concentration of the first coating
component varying continuously in a radial direction as claimed.” (App. Br.
21.) “[T]he Schwarz patent and the Chandrasekaran patent, alone or in
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combination, fails to disclose, teach, or suggest each and every element of
the Appellant's invention as claimed.” (App. Br. 19.)
We agree with the Appellants’ position. We find that the Examiner
has not adequately explained why the cited references would have prompted
an ordinary artisan to change the sequential layer therapeutic agent profile of
the Schwarz stents (FF11) and replace this with a continuous and/or linear
deposition profile. The Examiner reasons that because “Schwarz discloses
applying two coating components simultaneously and varying the
concentrations of coating components across a thickness of the coating.
Chandrasekaran is relied upon only for its teaching of linearly varying
concentrations of coating components. Schwarz already discloses a method
for applying two coatings simultaneously.” (Ans. 11; FF12.) The Examiner
asserts that “[a] linear concentration gradient would allow [for a] more
continuous and accurate control of the release profile of the active agents in
the Schwarz stent.” (Ans. 12.) However, Schwarz already disclosed varying
the concentration of components radially from the stent surface outward by
applying multiple layers, each having a different component concentration
(FF11). The sequential applications of multiple thin coatings would result in
a near linear concentration profile as recognized in the Specification (FF4).
The Examiner acknowledges that an ordinary artisan would “recognize that
these deposition methods [of Chandrasekaran] are not necessary for
achieving a linear concentration gradient in a stent. Although no specific
coating method is claimed, Examiner notes that such a concentration profile
could be achieved by any number of well known coating methods including,
for example, vapor deposition.” (Ans. 9-10.) What is missing from the
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Examiner's analysis is a reason that would have prompted the artisan to seek
ways of creating a linear gradient deposition on a stent in the first place. See
KSR, 550 U.S at 418 (obviousness rejections require “some articulated
reasoning with some rational underpinning”).
The preponderance of evidence on this record fails to support
Examiner's finding that Schwarz and Chandrasekaran teaches Appellants'
claimed invention. The rejection of claim 1 under 35 U.S.C. § 103(a) as
being obvious over Schwarz in view of Chandrasekaran is reversed. As
claims 2, 10, 11 and 44-65 have not been argued separately, they stand
claim 1. 37 C.F.R. § 41.37(c)(vii).

SUMMARY
We reverse the rejection of claims 1, 2, 5-7, 9-11, 14-16, and 18 under
35 U.S.C. § 103(a) as unpatentable over Tuch in view of Chandrasekaran.
We reverse the rejection claims 8 and 17 under 35 U.S.C. § 103(a) as
unpatentable over Tuch in view of Chandrasekaran and further in view of
Harish.
We reverse the rejection of claims 1, 2, 10, 11 and 44-65 under 35
U.S.C. § 103(a) as unpatentable over Schwarz in view of Chandrasekaran.

REVERSED

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