Ex Parte Song

Board of Patent Appeals and Interferences

Jun 1, 2011

10638920 (B.P.A.I. Jun. 1, 2011)

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.
10/638,920 08/11/2003 Young-Ho Song 02-428 (4010/43) 5977
27774 7590 06/02/2011
MAYER & WILLIAMS PC
251 NORTH AVENUE WEST
Suite 201
WESTFIELD, NJ 07090
EXAMINER
VU, JAKE MINH
ART UNIT PAPER NUMBER
1618
MAIL DATE DELIVERY MODE
06/02/2011 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 YOUNG-HO SONG
__________

Appeal 2010-012224
Application 10/638,920
Technology Center 1600
__________

Before ERIC GRIMES, MELANIE L. McCOLLUM, and STEPHEN
WALSH, Administrative Patent Judges.

GRIMES, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a medical
device. The Examiner has rejected the claims for obviousness and,
provisionally, for obviousness-type double patenting. We have jurisdiction
under 35 U.S.C. § 6(b). We affirm.
STATEMENT OF THE CASE
The Specification discloses that “[i]mplantable or insertable medical
devices are frequently used for delivery of one or more therapeutic agents”
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(Spec. 1, ¶ 0002). “Many therapeutic agents, however, are oxidation-
sensitive. This characteristic can adversely impact the shelf life and efficacy
of medical devices containing such therapeutic agents” (id. at 1, ¶ 0003).
Claims 1-4, 6, 8-11, 15-17, 19-22, 26, and 27 are on appeal. Claims 1,
8, and 10 are representative and read as follows:
1. A medical device comprising a medical device substrate and a
therapeutic-agent containing region over said substrate, wherein said
therapeutic-agent-containing region comprises trans-retinoic acid and an
antioxidant in an amount chosen so that the amount of the therapeutic agent
that is present in unoxidized form in the medical device after three weeks of
atmospheric exposure at 25°C is at least 10 times greater than the amount of
the therapeutic agent that is present in unoxidized form in the medical device
after three weeks of atmospheric exposure at 25°C in the absence of said
antioxidant.

8. The medical device of claim 1, wherein said therapeutic-agent
containing region further comprises a polymer.

10. The medical device of claim 8, wherein said polymer is a
polystyrene-polyisobutylene-polystyrene triblock copolymer.

The claims stand rejected as follows:
• Claims 1-4, 6, 8, 16, 19-22, 26, and 27 under 35 U.S.C. § 103(a) as
being obvious over Carlyle1 in view of Herdeg2 and/or Ishii;3

1 Carlyle et al., US 2003/0204239, Oct. 30, 2003
2 Christian Herdeg et al., Effects of local all-trans-retinoic acid delivery on
experimental atherosclerosis in the rabbit carotid artery, 57 CARDIO-
VASCULAR RESEARCH 544-553 (2003)
3 Ishii et al., US 6,833,004, Dec. 21, 2004
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• Claims 1-4, 6, 8-11, 15-17, 19-22, 26, and 27 under 35 U.S.C.
§ 103(a) as being obvious in view of Carlyle, Herdeg, Ishii, Davila4 and
Bales.5
• Claims 1-4, 6, 8-11, 15-17, 19-22, and 26-27 (provisionally) for
obviousness-type double patenting based on Application No. 10/955,368,
Carlyle, and Herdeg.
I.
Issue
The Examiner has rejected claims 1-4, 6, 8, 16, 19-22, 26, and 27
under 35 U.S.C. § 103(a) as being obvious over Carlyle in view of Herdeg
and/or Ishii. Claims 2-4, 6, 8, 16, 19-22, 26, and 27 have not been argued
separately and therefore stand or fall with claim 1. 37 C.F.R.
§ 41.37(c)(1)(vii).
The Examiner finds that Carlyle discloses a stent comprising “a
therapeutic agent, such as rapamycin to reduce restenosis (see [0034]) ;
[and] antioxidants, such as butylated hydroxytoluene … to prevent the
stabilized drug from degrading” (Answer 6-7). The Examiner finds that
Herdeg and Ishii both disclose trans-retinoic acid to inhibit vascular
restenosis (id. at 7). The Examiner concludes that it “would have been
obvious to the person of ordinary skill in the art … to incorporate trans-
retinoic acid into CARLYLE’s stent composition … because CARLYLE
disclosed using a therapeutic agent that inhibits restenosis and … trans-
retinoic acid is well-known to inhibit restenosis” (id.). The Examiner

4 Davila et al., US 2002/0111590, Aug. 15, 2002
5 Bales et al., US 6,527,938, Mar. 4, 2003
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reasons that although the references do not explicitly disclose the amount of
antioxidant recited in claim 1, the amount of an ingredient “in a composition
is clearly a result effective parameter that a person of ordinary skill in the art
would routinely optimize” (id. at 7-8).
Appellant contends that one of skill in the art would not have been
motivated combine the trans retinoic acid of either Herdeg or Ishii with the
stent of Carlyle (Appeal Br. 5-6) and that the cited references do not suggest
the claimed amount of antioxidant (id. at 7).
The issue with respect to this rejection is: Does the evidence of
record support the Examiner’s conclusions that it would have been obvious
to combine the trans retinoic acid of Herdeg or Ishii with the stent of Carlyle
and that the claimed amount of antioxidant does not distinguish the claimed
device from the prior art?
Findings of Fact
1. Carlyle discloses “catheter-deployed endovascular stents with
polymeric coatings including one or more drugs with desired timed-release
properties and a preservative containing at least one antioxidant” (Carlyle
2, ¶ 0021).
2. Carlyle discloses “the use of an effective amount of preservatives
in either the drug or polymer of a drug coated stent … to reduce or prevent
drug and polymer degradation” (id. at 2, ¶ 0023).
3. Carlyle discloses that “[e]xamples of preservatives that may be
used include antioxidants such as butylated hydroxytoluene (BHT) or
vitamins A through E” (id.).
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4. Carlyle discloses that the drug or “bioactive agent may be selected
to inhibit vascular restenosis” (id. at 3, ¶ 0032).
5. Carlyle discloses that the “bioactive agent may include …
rapamycin…. Rapamycin or sirolimus is a medication that may interfere
with the normal cell growth cycle and may be used to reduce restenosis.”
(Id. at 3, ¶ 0034.)
6. Herdeg discloses that “[a]ll-trans retinoic acid (atRA) is known to
inhibit smooth muscle cell growth and thus is supposed to have favorable
effects on the incidence of restenosis after percutaneous coronary
interventions” (Herdeg, abstract).
7. Herdeg discloses that “[i]n order to avoid systemic side effects,
local delivery of atRA is preferable” (id.).
8. Herdeg discloses that “[l]ocal delivery of atRA led to limitation of
restenosis formation in [an] animal model. The concept of … local atRA
therapy might be a promising way to exploit the potential of atRA for
vascular indications.” (Id.)
9. Ishii discloses a stent that provides “sustained release of [a]
biologically/physiologically active substance, namely, slow, gradual release
of the biologically/physiologically active substance for a prolonged period”
(Ishii, col. 3, ll. 21-25).
10. Ishii discloses that “[e]xemplary biologically/physiologically
active substances include … retinoid” (id. at col. 7, ll. 54-59).
11. Ishii discloses that “[e]xemplary preferred retinoids include all-
trans retinoic acid” (id. at col. 8, ll. 29-30).
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Analysis
Carlyle discloses endovascular stents with polymeric coatings
including a drug and an antioxidant to inhibit oxidative degradation of the
drug or polymeric coating. Carlyle discloses that the drug may be one that
inhibits restenosis. Herdeg discloses that local delivery of all-trans retinoic
acid (atRA) inhibited restenosis formation in an animal model and might be
promising for vascular indications. Ishii discloses a stent that provides
sustained-release delivery of drugs, including all-trans retinoic acid. In view
of these disclosures, it would have been obvious to one of ordinary skill in
the art to modify Carlyle’s stent to include all-trans retinoic acid, because
Herdeg and Ishii disclose that atRA inhibits restenosis and can be included
in a stent for sustained release.
Appellant argues that those of skill in the art would not have been
motivated to combine Herdeg’s trans-retinoic acid with Carlyle’s stent
because the atRA of Herdeg “is delivered via a double balloon catheter and
not with any type of coated stent” (Appeal Br. 5).
This argument is not persuasive. Although Herdeg uses an animal
model to investigate the anti-restenosis effects of atRA, one of skill in the art
would have considered it obvious to combine Herdeg’s atRA with the
Carlyle’s stent in view of Herdeg’s disclosure that atRA is effective as an
anti-restenosis agent and Carlyle’s express suggestion of stents that contain
anti-restenosis agents.
Appellant also argues that Ishii is not combinable with Carlyle or
Herdeg because Ishii’s stent requires the use of a polymer layer that releases
drugs when it swells and cracks (Appeal Br. 5-6). This argument is also
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unpersuasive because the Examiner’s rejection is not based on combining
the stents of Carlyle and Ishii, but only on the obviousness of substituting
all-trans retinoic acid, a known anti-restenosis agent (Herdeg) that had been
used in stents (Ishii), for the anti-restenosis agent rapamycin suggested by
Carlyle for use in its stent.
Appellant also argues that the cited references do not suggest the
claimed amount of antioxidant and that the Examiner was in error in
reasoning that claimed amount of antioxidant would be a result-effective
variable that would be routinely optimized because Carlyle discloses
competing goals of inhibiting corrosion of metallic stents or degradation of
polymeric stents (Appeal Br. 7).
This argument is not persuasive. Claim 1 simply requires a sufficient
level of antioxidant to maintain the drug in unoxidized form for a given
period of time under specified conditions. Appellants have provided no
evidence to show that amount of antioxidant required to achieve this level
would have been outside the range of amounts that would have been used
routinely, or that the amount would have been incompatible with
maintaining the integrity of metallic or polymeric stents.
Conclusion of Law
The evidence of record supports the Examiner’s conclusions that it
would have been obvious to combine Herdeg’s trans-retinoic acid with
Carlyle’s stent and that the claimed amount of antioxidant does not
distinguish the claimed device from the prior art.
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II.
Issue
The Examiner has rejected claims 1-4, 6, 8-11, 15-17, 19-22, 26, and
27 under 35 U.S.C. § 103(a) as being obvious in view of Carlyle, Herdeg,
Ishii, Davila and Bales. Since we have affirmed the rejection of claim 1 in
view of Carlyle, Herdeg and Ishii as discussed above, we also affirm the
rejection of claim 1 in view of Carlyle, Herdeg, Ishii, Davila and Bales.
Claims 2-4, 6, 8, 11, 15-17, 19-22, 26 and 27 fall with claim 1.
Appellants have argued claims 9 and 10, as a group, separately. The
Examiner relies on Carlyle, Herdeg, and Ishii, as discussed above. The
Examiner finds that Bales discloses “that in the field [of] stents, stable
biocompatible copolymers, such as polystyrene-polyisobutylene-polystyrene
polymers (SIBS) are used to coat the stent” (Answer 10). The Examiner
concludes that it “would have been obvious to the person of ordinary skill in
the art … to incorporate a copolymer, such as polystyrene-polyisobutylene-
polystyrene polymers, into CARLYLE’s stent composition … because
BALES teaches that in the field [of] stents, stable biocompatible
copolymers, such as polystyrene-polyisobutylene-polystyrene polymers
(SIBS) are commonly used to coat the stent” (id.).
Appellant contends that Bales teaches away from using “polymeric
binding materials … [because] BALES is directed to methods of forming
alternative coatings that can be loaded with biological or chemical agents
without resorting to the use of such polymeric binders” (Appeal Br. 8).
The issue with respect to this rejection is: Does the evidence of
record support the Examiner’s conclusion that one of ordinary skill in the art
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would have considered it obvious to combine Bale’s polystyrene-
polyisobutylene-polystyrene copolymer with the stent suggested by the
combination of Carlyle and Herdeg?
Additional Findings of Fact
12. Bales discloses a process to “create a fine microporous structure
on the surface of an implant article that would allow a biological or chemical
agent to be infiltrated into the surface of the article without the need for
binding agents” (Bales, col. 3, ll. 19-21).
13. Bales discloses that
others have coated stents … with biological agents … or
chemical agents … to reduce problems associated with hyper-
plasia or inflammation. In order to attach these biological or
chemical agents to the surface of a metallic stent, the agents
have been mixed with binders such as elastomers or bio-
resorbable polymers. These binders can also create problems in
that they can cause inflammation, and they can cause the
surface of the stent to have more friction, which reduces the
ease of stent delivery.
(Id. at col. 1, ll. 36-47.)
14. Bales discloses that
[i]n the field of arterial stents, coatings have been applied to
stainless steel and titanium alloys (e.g., TiNi alloys) to retard
tissue reactions such as thrombosis, inflammation, and
hyperplasia. Such coatings have been based upon stable bio-
compatible polymers (such as styrene-isobutylene-styrene
(SIBS)).… In the work known to date, the active chemical or
biological agent is mixed with the polymeric coating material,
and the agent then elutes from the coating once the implant is
placed in the body.
(Id. at col. 2, ll. 24-32.)
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Principles of Law
“A reference may be said to teach away when a person of ordinary
skill, upon reading the reference, would be discouraged from following the
path set out in the reference, or would be led in a direction divergent from
the path that was taken by the applicant. ” In re Gurley, 27 F.3d 551, 553
(Fed. Cir. 1994).
“[I]n a section 103 inquiry, ‘the fact that a specific [embodiment] is
taught to be preferred is not controlling, since all disclosures of the prior art,
including unpreferred embodiments, must be considered.’” Merck & Co.
Inc. v. Biocraft Laboratories Inc., 874 F.2d 804, 807 (Fed. Cir. 1989).
Analysis
Claim 10 depends from claim 1 and requires that the therapeutic-agent
containing region further comprises a polystyrene-polyisobutylene-
polystyrene triblock copolymer.
As discussed above, the combination of Carlyle, Herdeg, and Ishii
suggests polymer-coated stents that comprise an antioxidant and trans-
retinoic acid as an active agent. Bales discloses that polymers are used as
binders for therapeutic agents and that coatings based upon polymers such as
styrene-isobutylene-styrene (SIBS) have been applied to stainless steel and
titanium alloy stents to inhibit tissue reactions. In view of these disclosures,
it would have been obvious to use the styrene-isobutylene-styrene polymers
of Bales in the stent made obvious by Carlyle, Herdeg, and Ishii to act as a
binder for trans retinoic acid and to inhibit tissue reactions.
Appellant argues that Bales teaches away from polymeric binding
materials in general because Bales is directed to alternative stent coatings
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that can be loaded with biological or chemical agents without the use of
polymeric binders (Appeal Br. 8). Appellant also argues that Bales teaches
that binders have been known to cause problems such as inflammation and
friction during delivery (id. at 9).
These arguments are not persuasive. Bales discloses that styrene-
isobutylene-styrene polymers are stable biocompatible polymers known in
the art for coating stents and binding active agents. The fact that Bales
teaches advantages for microporous surfaces as binding surfaces for active
agents and teaches that polymers generally, although not styrene-
isobutylene-styrene polymers specifically, have been known to be associated
with problems does not lead one of skill in the art away from the use of
styrene-isobutylene-styrene polymers because these specific polymers are
described as being stable, biocompatible, and well known for their use in
stents.
Conclusion of Law
The evidence of record supports the Examiner’s conclusion that one
of ordinary skill in the art would have considered it obvious to combine
Bale’s polystyrene-polyisobutylene-polystyrene triblock copolymer with the
stent suggested by the combination of Carlyle and Herdeg.
III.
The Examiner has provisionally rejected claims 1-4, 6, 8-11, 15-17,
19-22 and 26-27 in view of copending Application No. 10/955,368, Carlyle,
and Herdeg. Claims 2-4, 6, 8-11, 15-17, 19-22 and 26-27 have not been
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argued separately and therefore stand or fall with claim 1. 37 C.F.R.
§ 41.37(c)(1)(vii).
The Examiner relies on Carlyle and Herdeg as discussed above. The
Examiner finds that the ‘368 application claims a stent comprising a
polymeric region and phenolic compound, wherein the phenolic compound
is butylated hydroxytoluene (Answer 5). The Examiner concludes that it
“would have been obvious to the person of ordinary skill in the art … to
incorporate … trans-retinoic acid into the copending application … because
trans-retinoic acid inhibits vascular restenosis, which commonly occurs with
stent insertion into the vasculature vessels” (id.). We agree with and adopt
the Examiner’s findings and conclusion.
Appellant contends that the “rejection is … in error, based on the
deficiencies in CARLYLE and HERDEG” (Appeal Br. 3). This argument is
unpersuasive for the reasons discussed above with respect to obviousness.
SUMMARY
We affirm the rejection of claims 1-4, 6, 8-11, 15-17, 19-22, 26, 27
under 35 U.S.C. § 103(a). We also affirm the provisional obviousness-type
double patenting rejection of claims 1-4, 6, 8-11, 15-17, 19-22, 26, 27 in
view of copending Application No. 10/955,368, Carlyle, and Herdeg.

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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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