Ex Parte Jang

Patent Trial and Appeal Board

Sep 26, 2012

11332606 (P.T.A.B. Sep. 26, 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.
11/332,606 01/12/2006 Eun-Hyun Jang 04-0415 (4010/337) 6563
27774 7590 09/26/2012
MAYER & WILLIAMS PC
251 NORTH AVENUE WEST
Suite 201
WESTFIELD, NJ 07090
EXAMINER
FISHER, ABIGAIL L
ART UNIT PAPER NUMBER
1616
MAIL DATE DELIVERY MODE
09/26/2012 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 PATENT TRIAL AND APPEAL BOARD
__________

Ex parte EUN-HYUN JANG
__________

Appeal 2012-000140
Application 11/332,606
Technology Center 1600
__________

Before DEMETRA J. MILLS, ERIC GRIMES, and MELANIE L.
McCOLLUM, Administrative Patent Judges.

GRIMES, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a coated
medical device. 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 drug-eluting medical devices having a
coating that “comprises a biologically active material that is present in a first
form and a second form” (id. at 2:22-27). The Specification discloses that
the first form and second form “refer to the same biologically active material
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at different physical or chemical states,” and “can include … a free acid
form or a free base form or a salt form of the biologically active material”
(id. at 2:27 to 3:4).
Claims 1, 5-7, 9, 10, and 13-26 are on appeal. Claims 1 and 18 are
representative and read as follows:
1. A coated medical device comprising:
a medical device having a surface suitable for exposure to a body
tissue; and
a coating comprising one or more layers disposed on at least a portion
of the surface, wherein the coating comprises a first polymer and a
biologically active material,
wherein the biologically active material is present in a first form and a
second form,
wherein the coating releases the first form and the second form of the
biologically active material at different rates, and
wherein said medical device is selected from a vascular stents,
surgical staples, central venous catheters, arterial catheters, cardiac
pacemaker leads or lead tips, cardiac defibrillator leads or lead tips,
implantable vascular access ports, vascular grafts, heart valves,
cardiovascular sutures, total artificial hearts and ventricular assist pumps.

18. The coated medical device of [claim 1, wherein the coating
comprises a plurality of coating layers], wherein the plurality of coating
layers comprises a first coating layer and a second coating layer, wherein the
first coating layer comprises the first polymer and the first form of the
biologically active material, and wherein the second coating layer comprises
a second polymer and the second form of the biologically active material,
and wherein the first polymer and the second polymer may be the same or
different.

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The claims stand rejected under 35 U.S.C. § 103(a) as follows:
• Claims 1, 5-7, 9, 10, 13-20, and 22-26 in view of Nagler,1 Oshlack,2
and Rowland;3 and
• Claims 1, 5-7, 9, 10, and 13-26 in view of Nagler, Oshlack,
Rowland and Cheng.4
Issue
The Examiner has rejected most of the claims on appeal as obvious
based on Nagler, Oshlack, and Rowland, and has rejected all of the claims
on appeal based on Nagler, Oshlack, Rowland and Cheng. With respect to
both rejections, Appellant argues the claims in two groups: claims 5-7, 9, 10,
13-17, 22, and 24-26 stand or fall with claim 1; claims 19, 20, and 23 stand
or fall with claim 18. 37 C.F.R. § 41.37(c)(1)(vii).
The Examiner finds that Nagler discloses “intracoronary stents
containing quinazolinone derivatives,” preferably halofuginone (Answer 4).
The Examiner finds that Nagler’s “Example 1 is directed to the coating of a
metal stent with a polymeric matrix comprising … polyethylene vinyl
acetate and 0.1 % of halofuginone free base” (id. at 4-5). The Examiner
finds that Nagler discloses that the “hydrophilicity or hydrophobicity of the
polymer carrier will determine the release rate of halofuginone,” that both

1 Nagler et al., US 6,159,488, Dec. 12, 2000.
2 Oshlack et al., US 4,443,428, Apr. 17, 1984.
3 Rowland et al., Patent Application Publication US 2004/0039441 A1, Feb.
26, 2004.
4 Cheng, Patent Application Publication US 2004/0215313A1, Oct. 28,
2004.
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hydrophilic and hydrophobic polymers may be used, and that the drug
release profile depends on several factors (id. at 5).
The Examiner finds that Oshlack discloses a “pharmaceutical
composition comprising a slow release matrix having dispersed therein both
the pharmacologically active [salt] form … and the free base form [of] the
same medication” (id. at 6). The Examiner finds that Oshlack discloses that
the dissolution rate of the active substance is “extended when a balanced
proportion of the pharmacologically active moiety in its free or base form is
combined with the salt form of the substance in the slow release matrix”
(id.). The Examiner finds that Rowland discloses a medical device having a
coating that “comprises one or more pharmaceutical substances incorporated
into a polymer matrix so that the pharmaceutical substance is released … in
a slow or controlled-release manner” (id.), where the “release kinetics of a
drug … depends on the hydrophobicity of the drug” (id. at 7).
The Examiner concludes that it would have been obvious to
“incorporate both the free base and salt form of the drug into the polymer
matrix of Nagler et al. as a different way of manipulating the release rate of
the drug” (id. at 8) because Oshlack discloses that using “both forms of a
drug in a slow release matrix can provide a sustained extended release of the
active moiety” and Rowland discloses that “a hydrophobic drug releases at a
slower rate than a hydrophilic drug and that manipulation of the release rate
of a drug from a polymeric matrix is desirable for stent coatings” (id.).
Appellant contends that Oshlack is non-analogous art to Rowland and
Nagler (Appeal Br. 6-7) and that, even if the references were combined, they
would not have made obvious a coated medical device comprising “a
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combination of a biologically active material in a first form (i.e., free base
form) and a second form (i.e., a salt form),” as required by claim 1 (Appeal
Br. 7-8). Appellant also argues that a skilled worker would not have had a
reasonable expectation that the coated stent asserted by the Examiner would
be successful (id. at 8).
The issues presented are: Does the evidence of record support the
Examiner’s conclusion that the cited references would have made obvious a
medical device comprising a coating with a “biologically active material …
in a first form and a second form, wherein the coating releases the first form
and the second form … at different rates,” as recited in claim 1, and a
coating having the first and second layers required by claim 18?
Findings of Fact
1. Nagler discloses “a stent coated with a composition for the
inhibition of restenosis, comprising a quinazolinone derivative … as active
ingredient” (Nagler, col. 1, ll. 12-17).
2. Nagler discloses that the quinazolinone derivative can be either the
free base form, or a salt (id. at col. 10, ll. 2-23; col. 7, ll. 64-67).
3. Nagler discloses that halofuginone is a preferred quinazolinone
derivative (id. at col. 1, ll. 28-30; col. 3, ll. 1-2).
4. Nagler discloses a metal stent coated with halofuginone in a
polymer carrier (id. at col. 7, l. 63 to col. 8, l. 1).
5. Nagler discloses that the “hydrophilicity or hydrophobicity of the
polymer carrier will determine the release rate of halofuginone from the
stent surface” (id. at col. 8, ll. 18-20).
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6. Nagler exemplifies a stent coated with a polymer coating
comprising polyethylene vinyl acetate and halofuginone free base by dipping
the stent in the coating (id. at col. 7, l. 63 – col. 8, l. 1).
7. Nagler discloses that if a “thicker coating is desired, the dipping
process is repeated several times” (id. at col. 8, ll. 1-3).
8. Nagler discloses that
[t]he drug release profile … can be altered by altering the
coating thickness, the polymer carrier, the drug content in the
polymer, composition of the coating (hydrophilic or
hydrophobic additives; blends of polymers), the drug content
within the various layers of coating, the configuration of the
stent, and the properties of the rate-controlling membrane.
(Id. at col. 8, ll. 50-56.)
9. Oshlack discloses extended release pharmaceutical compositions
(Oshlack, col. 3, ll. 13-16).
10. Oshlack discloses that “the dissolution rate of a pharma-
cologically active substance from a slow release composition is materially
extended when a balanced proportion of the pharmacologically active
moiety in its free or base form is combined with the salt form of the
substance in the slow release matrix” (id. at col. 3, ll. 52-57).
11. Oshlack discloses that
the use of the electrically uncharged and lipid favoring base
material does not accelerate dissolution time or stimulate
absorption, and therefore increases bioavailability as taught in
the prior art, but rather slows absorption and extends
dissolution time and bioavailability.
(Id. at col. 5, ll. 1-7.)
12. Oshlack provides several working examples showing that the
addition of the free base form of a pharmaceutical to the salt form of the
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same pharmaceutical extends the dissolution time of the dosage form, as
compared to a dosage form containing the salt form alone, in simulated
intestinal juice (id. at col. 12, ll. 35-59; col. 14, ll. 1-20; col. 15, ll. 12-38;
col. 16, ll. 45-60).
13. Rowland discloses medical devices such as “stents and synthetic
grafts which are coated with a controlled-release matrix comprising a
medicinal substance” (Rowland 1, ¶ 0002).
14. Rowland discloses that the matrix comprises “a bioabsorbable
material … and at least one pharmaceutical substance or composition for …
[delivery] to the site of implantation. The pharmaceutical substance …
inhibits smooth muscle cell migration, and prevents restenosis.” (Id. at 2,
¶ 0018.)
15. Rowland discloses that the “release of the pharmaceutical
substance in a controlled manner allows for smaller amounts of drug or
active agent to be released for a long period of time” (id. at 4, ¶ 0033).
16. Rowland discloses that “the release kinetics of a drug further
depends on the hydrophobicity of the drug, i.e., the more hydrophobic the
drug is, the slower the rate of release of the drug from the matrix” (id.).
17. Rowland discloses that the “matrix composition can be altered
according to the drug to be delivered in order to maintain the concentration
of drug required at the site for a longer period of time … [which] is more
efficient in preventing restenosis and minimizes the side effects of the
released pharmaceutical substances” (id.).
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Principles of Law
Even when prior art is not in the same field of endeavor as the claimed
invention, it is still analogous prior art if it is “reasonably pertinent to the
particular problem with which the inventor is involved.” In re Bigio, 381
F.3d 1320, 1325 (Fed. Cir. 2004).
“A reference is reasonably pertinent if, even though it may be in a
different field from that of the inventor's endeavor, it is one which, because
of the matter with which it deals, logically would have commended itself to
an inventor’s attention in considering his problem.” In re Clay, 966 F.2d
656, 659 (Fed. Cir. 1992).
Analysis
Claim 1 is directed to a medical device having at least a partial
coating comprising a polymer and a biologically active material in two
different forms with different rates of release. Nagler discloses stents coated
with compositions containing a polymer carrier and a quinazolinone
derivative, preferably halofuginone, to inhibit restenosis. Nagler discloses
that the halofuginone can be used in a free base form or a salt form, and
discloses that the release profile depends on various factors.
Oshlack discloses extended release pharmaceutical compositions
comprising an active agent in free base form and in a salt form. Rowland
discloses stents which are coated with a controlled-release matrix
comprising a medicinal substance to prevent restenosis. Rowland also
discloses that hydrophobic drugs are released from the matrix at a slower
rate than hydrophilic drugs, and that the matrix composition can be altered
according to the drug to be delivered.
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In view of these disclosures, it would have been obvious to one of
ordinary skill in the art to construct Nagler’s stent with a surface coating that
comprises a polymer and both the free base form and a salt form of
halofuginone, because Rowland teaches that the release rate of
pharmaceutical agents from a coating matrix depends on the hydrophobicity
or hydrophilicity of the active substances, and because Oshlack discloses
that the release rate of an active substance can be controlled by combining
the free base and salt form of the substance in a composition.
Appellant argues that Oshlack cannot be properly combined with
Nagler and Rowland because the references “constitute nonanalogous art,
with the teachings regarding the salt and base forms in the oral tablets of
Oshlack having no pertinence to the stents in Rowland and Nagler” (Appeal
Br. 7). Appellant cites evidence showing that simulated gastric juice and
simulated intestinal juice, as used by Oshlack, have pHs of 1.2 and 7.50
respectively, which is different from that of the vascular environment (pH ~
7.4) (id. at 6).
This argument is unpersuasive. All of the references relate to the
formulation of slow release compositions for the delivery of pharmaceutical
agents. Thus, all of the references relate to the same field of endeavor, even
if the slow release compositions were targeted to different tissues. In
addition, even if Oshlack was not in the same field of endeavor as the
claimed invention, it is still pertinent to the problem involved, because
Oshlack pertains to the problem of formulating slow release compositions.
Finally, Appellant’s own evidence shows that the pH of simulated intestinal
juice is very close to that of the vascular environment, and therefore
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provides no basis for concluding that Oshlack’s findings would not have
been considered pertinent to the stents of Nagler and Rowland.
Appellant argues that one of ordinary skill in the art would “at best,
employ a composition comprising 100% of the hydrophobic (base) form in
order to ‘maintain the concentration of the drug required for a longer period
of time which is more efficient in preventing restenosis and minimizing the
side effects of the pharmaceutical substances.’” (Appeal Br. 85). Appellant
argues that “there would be no reason to employ a combination of a
biologically active material in a first form (i.e., free base form) and a second
form (i.e., a salt form) as claimed” (id.).
As we understand it, Appellant’s argument is that, because Rowland
teaches the desirability of maintaining the concentration of a drug over a
long period of time and teaches that a hydrophobic drug is released more
slowly, at best it would have been obvious to use only a hydrophobic (base)
form of a drug in order to maximize the length of time that it is released.
The argument is not persuasive.
Oshlack expressly discloses that it is the “balanced combination of a
salt . . . and the free active base” (Oshlack, col. 3, ll. 18-19, emphasis added)
that provides the beneficial slow release of its composition. Oshlack also
discloses that the salt form and free base form can be mixed in different
proportions (id. at col. 3, ll. 46-51), but does not teach using 100% base
form. In addition, Oshlack discloses that “solubility, per se, is not found to
be a controlling factor” (id. at col. 5, ll. 8-9) in its combination of a salt form

5 Appellant does not provide a citation for the quoted passage. The
“quotation” appears to be a paraphrasing of Rowland’s ¶ 0033.
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and free base form of a pharmaceutical. Thus, we agree with the Examiner’s
conclusion that a skilled worker familiar with both Rowland and Oshlack
would have considered it obvious to use a combination of a free base form
and a salt form of a given pharmaceutical in a stent coating.
Appellant argues that due to “differences between the gastrointestinal
environment and the vascular environment (including pH and enzymatic
content), there would not be a reasonable expectation that one could
successfully achieve results in a vascular environment that are like those
observed in a gastrointestinal environment” (Appeal Br. 8).
This argument is not persuasive. As discussed above, Appellant’s
evidence shows that simulated intestinal juice has a pH similar to the
vascular pH. Appellant’s argument that the gastrointestinal and vascular
environments differ in enzymatic content is not persuasive because
Appellant has not explained why one of skill in the art would expect the
difference in enzymes to affect dissolution rates.
Appellant argues that “[e]xpectations of success are particularly low in
the present case where the expected results in the gastrointestinal tablet art of
Oshlack are reversed relative to the expectations in the stent art of Rowland
(and Nagler)” (id., citing Oshlack, col. 5, ll. 1-7; Rowland, 4 ¶ 0033).
This argument is not persuasive. The cited passage in Oshlack states
that the use of the electrically uncharged and lipid favoring base material
extends dissolution time, and Rowland discloses that hydrophobic drugs are
released at a slower rate than hydrophilic drugs. Thus, the cited portions of
Oshlack and Rowland appear to be in agreement, not reversed as Appellant
argues.
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Appellant also argues that claim 18 would not have been obvious.
Claim 18 depends from claim 1 and further requires that the coating
comprises two layers that comprise, respectively, the first form and the
second form of the biologically active material. The Examiner concludes
that it would have been obvious to “utilize multiple coatings in order to
increase the coating thickness … [because] Nagler et al. teach that this is one
way [to] vary the thickness of the coating as well as effect [sic] the drug
release profile” (Answer 9). We agree with the Examiner’s reasoning.
Appellant argues that “[n]othing remotely resembling such a coating
[as required by claim 18] is found in Nagler, Oshlack and Rowland” (Appeal
Br. 8).
This argument is not persuasive. As discussed above, Nagler,
Oshlack, and Rowland, considered together, would have made obvious a
stent with a coating layer comprising a biologically active material in both
first form and a second form. Nagler discloses applying a thicker coating by
repeatedly dipping a stent in a coating composition. Repeated dipping a
stent in a coating composition comprising two forms of a biologically active
material would result in a stent with “a first coating layer and a second
coating layer, wherein the first coating layer comprises a first polymer and a
first form of the biologically active material and the second coating layer
comprises a second polymer and a second form of the biologically active
material,” as required by claim 18. While the two layers would each
comprise both the first and second form of the biologically active material,
claim 18’s “comprises” language does not exclude that result. Claim 18
explicitly allows the first and second polymer to be the same.
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Conclusion of Law
The evidence of record supports the Examiner’s conclusion that the
cited references would have made obvious a medical device comprising a
coating with a “biologically active material … in a first form and a second
form, wherein the coating releases the first form and the second form … at
different rates,” as recited in claim 1, and a coating having the first and
second layers required by claim 18.
SUMMARY
We affirm the rejection of claims 1, 5-7, 9-10 and 13-26 under 35
U.S.C. § 103(a).
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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