Ex Parte Keeley et al

Patent Trial and Appeal Board

May 13, 2013

12137923 (P.T.A.B. May. 13, 2013)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte DANIEL J. KEELEY,
TERRI A. KAPUR, and GREG M. SCHORN
__________

Appeal 2011-012221
Application 12/137,923
Technology Center 3700
__________

Before FRANCISCO C. PRATS, JACQUELINE WRIGHT BONILLA, and
SHERIDAN K. SNEDDEN, Administrative Patent Judges.

PRATS, Administrative Patent Judge.

DECISION ON APPEAL
This appeal under 35 U.S.C. § 134 involves claims to a process of
intermittently dispensing a drug to a patient. The Examiner entered
rejections for obviousness.
We have jurisdiction under 35 U.S.C. § 6(b). We reverse.
STATEMENT OF THE CASE
The Specification discloses that one of the biggest challenges in
administering drugs to the brain through intracranial catheters is
unpredictability in the drugs‟ distribution in the target tissue, caused by
“backflow of the infused agent along the catheter‟s insertion track” (Spec.
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3). The Specification explains that, as the infused drug permeates the tissue
surrounding the catheter, the tissue “gradually experiences „creep‟
phenomena, whereby the fluid slowly flows alongside the exterior of the
catheter, displacing the surrounding tissue until eventually the surrounding
tissue no longer seals the catheter track and fluid reaches the entrance point
of the catheter into the tissue,” ultimately resulting in “an undesirable drug
distribution to adjacent non-target tissues” (id.).
Appellants‟ invention is directed to avoiding this problem by
dispensing the drug in pulsed intervals that allow the drug-infused tissue to
recover its shape, or recoil, against the catheter surface during periods of
reduced drug dispensation, “thereby maintaining or re-establishing a seal of
the tissue around the catheter and thus preventing fluid backflow along the
catheter track” (id. at 4).
Claims 1-14 stand rejected and appealed (App. Br. 2). Claims 1 and
9, the independent claims, illustrate the appealed subject matter and read as
follows:
1. A method of treating a mammal comprising the steps of:
a. introducing a catheter into a distensible tissue of a
mammal, said catheter being operably connected
to a drug delivery pump, and
b. intermittently operating said drug delivery pump
for one or more predetermined intervals of time to
generate a pulsatile flux of drug through said
catheter into said tissue,
wherein said time intervals of intermittent pump operation allow
sufficient time for said distensible tissue to recoil around said catheter,
thereby preventing backflow of said drug along outer wall of said
catheter.

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9. A method of treating a mammal comprising the steps of:
a. introducing a catheter into a distensible tissue of a
mammal, said catheter being operably connected
to a drug delivery pump, and
b. operating said drug delivery pump at two or more
predetermined rates of flow over two or more
predetermined time intervals to generate a pulsatile
flux of drug through said catheter into said tissue,
wherein the combination of said two or more predetermined rates of
flow over two or more predetermined time intervals allow sufficient
time for said distensible tissue to recoil around said catheter, thereby
preventing backflow of said drug along outer wall of said catheter.

The following rejections are before us for review:
(1) Claims 1, 8, 11, and 12, under 35 U.S.C. § 103(a) as obvious over
Starkebaum
1
and Kratoska
2
(Ans. 4-5);
(2) Claims 2-7, under 35 U.S.C. § 103(a) as obvious over Starkebaum,
Kratoska, and Fiering
3
(Ans. 5-7);
(3) Claim 10, under 35 U.S.C. § 103(a) as obvious over Starkebaum,
Kratoska, and Kunst
4
(Ans. 7);
(4) Claim 9, under 35 U.S.C. § 103(a) as obvious over Jasperson
5
and
Kratoska (Ans. 8); and
(5) Claims 13 and 14, under 35 U.S.C. § 103(a) as obvious over
Jasperson, Kratoska, and Kunst (Ans. 9).

1
U.S. Patent App. Pub. No. 2003/0204181 A1 (published Oct. 30, 2003).
2
U.S. Patent No. 6,090,072 (issued Jul. 18, 2000).
3
U.S. Patent App. Pub. No. 2008/0009836 A1 (published Jan. 10, 2008).
4
U.S. Patent App. Pub. No. 2004/0215173 A1 (published Oct. 28, 2004).
5
U.S. Patent App. Pub. No. 2004/0077997 A1 (published Apr. 22, 2004).
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OBVIOUSNESS – STARKEBAUM AND KRATOSKA
The Examiner found that Starkebaum described a process of using a
catheter to administer a drug into a mammal‟s distensible tissue,
substantially as required by claim 1, including delivering the drug by
“intermittently operating [a] drug delivery pump for one or more
predetermined intervals of time to generate a pulsatile flux of drug through
said catheter into said tissue” (Ans. 4 (citing Starkebaum [0060], [0080], and
Fig. 14)).
The Examiner found that Starkebaum differed from claim 1 in that,
although “Starkebaum discloses periods of time between pumped deliveries
(Para 60), [Starkebaum] does not disclose the length of those periods” (id.).
The Examiner cited Kratoska as evidence that an ordinary artisan
would have been prompted to modify the timing of Starkebaum‟s pulsed
drug delivery so as to allow sufficient time for the distensible tissue to recoil
around the catheter, and thereby prevent backflow of the drug along the
catheter‟s outer wall, as claim 1 requires (see id. at 4-5).
Specifically, the Examiner cited Kratoska as describing a process of
delivering a drug through a catheter
wherein time interval after insertion of the catheter but prior to
pump operation allows sufficient time for said distensible tissue
to recoil around said catheter, thereby preventing backflow of
fluids along outer wall of said catheter (Col 25, Lines 8-23) for
the purpose of diminishing the amount of fluid that exits the
treatment site (Col 25, Lines 20-21).

(Id. at 4-5.)
Therefore, the Examiner reasoned, an ordinary artisan would have
considered it obvious to “modify Starkebaum to include time for the
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distensible tissue to recoil around said catheter, as taught by Kratoska et al.,
for the purpose of diminishing the amount of fluid that exits the treatment
site (Col 25, Lines 20-21)” (id. at 5).
As stated in In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992):
[T]he examiner bears the initial burden . . . of presenting a
prima facie case of unpatentability. . . .
After evidence or argument is submitted by the applicant
in response, patentability is determined on the totality of the
record, by a preponderance of evidence with due consideration
to persuasiveness of argument.

Ultimately, “[i]n determining whether obviousness is established by
combining the teachings of the prior art, the test is what the combined
teachings of the references would have suggested to those of ordinary skill
in the art.” In re GPAC Inc., 57 F.3d 1573, 1581 (Fed. Cir. 1995) (internal
quotations omitted).
We agree with Appellants that a preponderance of the evidence does
not support the Examiner‟s finding that Kratoska would have suggested
modifying the timing of Starkebaum‟s pulsed drug delivery so as to allow
sufficient time for the tissue to recoil around the catheter, and thereby
prevent backflow of the drug along the catheter‟s outer wall, as required by
claim 1.
We agree with the Examiner that Starkebaum introduces its drug
through a catheter placed in the brain, a tissue Appellants do not dispute is
distensible (see Starkebaum, Fig. 14). In contrast to delivering drugs to the
brain, however, Kratoska is directed to an expandable sheath that allows
introduction of intravascular catheters, such as angioplasty catheters, into a
patient‟s blood vessels (see Kratoska, abstract; see also id. at col. 1, ll. 9-45).
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As Kratoska explains, expandable introducer sheaths are desirable
because “larger size intravascular devices require the use of a larger size
introducer sheath and accordingly, necessitate exchanging [a] first introducer
sheath for another introducer sheath having a larger inner diameter” (id. at
col. 3, ll. 17-21). Thus, in one embodiment, Kratoska‟s sheath is made of a
shape memory material allowing it to return to its original diameter after
having been expanded to a larger size (see id., abstract).
In the embodiment cited by the Examiner, Kratoska‟s sheath includes
ribs that create a space between the sheath and dilator allowing for drug
infusion (see id. at col. 24, ll. 44-56). Kratoska discloses that, if desired,
“the sheath 200 can be reduced to its original smaller diameter state by
simply removing the larger intravascular device 214 which allows the sheath
shaft 206 to contract back to its original diameter by virtue of the
elastomeric material characteristics” (id. at col 24, ll. 62-66).
Kratoska discloses, however, that, because expanding the sheath also
expands the opening in the vessel wall, “when the intravascular device 214
is removed and the sheath 200 contracts back to its smaller original
diameter, blood may flow through the puncture site 56 around the sheath”
(id. at col. 25, ll. 4-7). Kratoska discloses that this problem of blood
“„backflow‟” can be avoided by using a dilator having a tapered or stepped
diameter which is gradually withdrawn from the sheath so as to allow the
blood vessel opening to, in turn, “gradually viscoelastically recover and
retighten. This diminishes the amount of blood flow exiting the vessel
around the outer diameter of the sheath 200 and because the rod dilator is
solid, blood flow through the sheath 200 is prevented” (id. at col. 25, ll. 8-
23).
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Accordingly, Kratoska explains, “the use of a tapered diameter rod
dilator, or „stepwise‟ tapered rod dilator, increases the possibility of allowing
a hole in the vessel to recover and effectively seal about the original
diameter of the sheath shaft once the rod dilator is fully removed from the
sheath” (id. at col. 25, ll. 23-28).
We acknowledge Kratoska‟s teaching that, when performing
procedures such as angioplasty, gradually withdrawing a tapered dilating
element from an introducer sheath, so as to allow an expanded blood vessel
opening to more completely contract back to its original diameter, can avoid
blood backflow along the outside of the sheath. We are not persuaded,
however, that that teaching would have suggested to an ordinary artisan that
drug backflow would be a problem when using Starkebaum‟s brain-inserted
catheter. Indeed, the Examiner points to no clear or specific teaching in
either reference suggesting to an ordinary artisan that drug backflow in
Starkebaum‟s process was a problem that needed addressing.
Nor are we persuaded that Kratoska‟s teaching of a suitable method of
withdrawing an introducer sheath/catheter from a blood vessel would have
suggested to an ordinary artisan that the timing of drug delivery pulses to the
brain in Starkebaum‟s process should be modified so as to avoid the problem
of drug backflow along the outer wall of the brain-inserted catheter. We
acknowledge, as the Examiner argues (see Ans. 11), that Kratoska‟s device
delivers drugs. We are not persuaded, however, that the processes described
in the two references are sufficiently similar such that an ordinary artisan
would have reasoned that, because gradual withdrawal of an introducer
sheath used in a procedure such as angioplasty can avoid blood backflow,
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one should adjust the pulses of a drug intermittently delivered to the brain
through a catheter so as to avoid backflow of the drug along the catheter.
We are therefore not persuaded that the Examiner has adequately
explained why Kratoska would have prompted an ordinary artisan to modify
the timing of Starkebaum‟s pulsed drug delivery so as to allow sufficient
time for the tissue to recoil around the catheter, and thereby prevent
backflow of the drug along the catheter‟s outer wall, as required by claim 1.
As the Examiner has not adequately explained why a process having all of
the elements recited in claim 1 would have been obvious to an ordinary
artisan, we reverse the Examiner‟s rejection of that claim, as well as its
dependents, claims 8, 11, and 12, over Starkebaum and Kratoska.
In rejecting claims 2-7, which depend directly or ultimately from
claim 1, as obvious, the Examiner relied on Starkebaum and Kratoska for the
teachings discussed above, and cited Fiering as evidence that the relative
intervals of drug delivery pump operation recited in claims 2-7 would have
been obvious to an ordinary artisan (see Ans. 5-7). However, the Examiner
did not point to, nor do we see, any teaching or suggestion in Fiering that
remedies the shortcomings discussed above of Starkebaum and Kratoska as
to claim 1. We therefore reverse this rejection as well.
In rejecting claim 10, which depends from claim 1, as obvious over
Starkebaum, Kratoska, and Kunst, the Examiner again relied on Starkebaum
and Kratoska for the teachings discussed above, and cited Kunst as evidence
that it was known in the art to control drug flux by altering the number and
size of ports on a drug delivery catheter (see Ans. 7). Again, however, the
Examiner did not point to, nor do we see, any teaching or suggestion in
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Kunst that remedies the shortcomings discussed above of Starkebaum and
Kratoska as to claim 1. We therefore reverse this rejection as well.
OBVIOUSNESS – JASPERSON AND KRATOSKA
In rejecting claim 9 as obvious over Jasperson and Kratoska, the
Examiner applied a similar rationale to that discussed above when rejecting
claim 1 over Starkebaum and Kratoska (see Ans. 8). In particular, the
Examiner cited Jasperson as using a drug delivery pump operated at
different rates to achieve a pulsatile flow of drug to a patient through a
catheter. However, the Examiner conceded that although “Jasperson et al.
disclose periods of time for the deliveries (Fig 3, Table 1)[,] ... [Jasperson]
does not disclose that the combination of the intervals allows sufficient time
for said distensible tissue to recoil around said catheter” (id.).
The Examiner cited Kratoska as evidence that an ordinary artisan
would have been prompted to modify the timing of Jasperson‟s pulsed drug
delivery so as to allow sufficient time for the distensible tissue to recoil
around the catheter, and thereby prevent backflow of the drug along the
catheter‟s outer wall, as claim 9 requires (see id.).
We reverse this rejection as well.
We acknowledge Jasperson‟s disclosure of administering drugs, such
as pain medications, at different rates during different times of the day so as
to accommodate the patient‟s needs (see, e.g. Jasperson [0044]). We also
acknowledge that Jasperson does not appear to limit its catheter‟s entry point
to any particular tissue.
Again, however, the Examiner‟s arguments notwithstanding (see Ans.
13-14), the Examiner points to no clear or specific teaching in either
reference, or in the knowledge generally available to an ordinary artisan,
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suggesting to the artisan that drug backflow due to an excessive drug
infusion rate, or tissue permeation, was a problem in Jasperson‟s process that
needed addressing. Moreover, as noted above, Kratoska does not address its
problem of blood backflow by reducing its drug infusion rate.
Rather, as discussed above, Kratoska addresses the problem of blood
backflow from an expanded introducer sheath by gradually withdrawing a
tapered dilating element from the sheath, so as to allow an expanded blood
vessel opening to more completely contract to its original diameter. We are
not persuaded that Kratoska‟s teaching of a suitable method of withdrawing
an introducer sheath/catheter from a blood vessel in a procedure such as
angioplasty would have led an ordinary artisan to conclude that the timing of
Jasperson‟s pain drug delivery pulses process should be modified in a
manner that would avoid the problem of drug backflow, particularly given
the absence of any suggestion in either reference that drug backflow would
be a problem in Jasperson‟s process.
Thus, we are not persuaded that the Examiner has adequately
explained why Kratoska would have prompted an ordinary artisan to modify
the timing of Jasperson‟s pulsed drug delivery so as to allow sufficient time
for the tissue to recoil around the catheter, and thereby prevent backflow of
the drug along the catheter‟s outer wall, as required by claim 9. We
therefore reverse the Examiner‟s obviousness rejection of that claim over
those references.
In rejecting claims 13 and 14, which depend directly or ultimately
from claim 9, as obvious over Jasperson, Kratoska, and Kunst, the Examiner
relied on Jasperson and Kratoska for the teachings discussed above, and
cited Kunst as evidence that it was known in the art to treat brain tissue
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according to the methods suggested by Jasperson and Kratoska (see Ans. 9).
Again, however, the Examiner did not point to, nor do we see, any teaching
or suggestion in Kunst that remedies the shortcomings discussed above of
Starkebaum and Kratoska as to claim 9. We therefore reverse this rejection
as well.
SUMMARY
We reverse the Examiner‟s obviousness rejection of claims 1, 8, 11,
and 12 over Starkebaum and Kratoska.
We reverse the Examiner‟s obviousness rejection of claims 2-7 over
Starkebaum, Kratoska, and Fiering.
We reverse the Examiner‟s obviousness rejection of claim 10 over
Starkebaum, Kratoska, and Kunst.
We reverse the Examiner‟s obviousness rejection of claim 9 over
Jasperson and Kratoska.
We reverse the Examiner‟s obviousness rejection of claims 13 and 14
over Jasperson, Kratoska, and Kunst.

REVERSED

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