Ex Parte Johnson et al

Patent Trial and Appeal Board

Aug 28, 2015

10719007 (P.T.A.B. Aug. 28, 2015)

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.
10/719,007 11/20/2003 Randolph Mellus Johnson DURE-007CON2 9101
82893 7590 08/31/2015
BFF/Durect Corporation
Bozicevic, Field & Francis
Durect Corporation - Corporate Headquarters
10260 Bubb Road
Cupertino, CA 95014-4166
EXAMINER
GHALI, ISIS A D
ART UNIT PAPER NUMBER
1611
MAIL DATE DELIVERY MODE
08/31/2015 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 RANDOLPH MELLUS JOHNSON and FELIX THEEUWES
__________

Appeal 2012-0110931
Application 10/719,007
Technology Center 1600
__________

Before DONALD E. ADAMS, FRANCISCO C. PRATS, and
JEFFREY N. FREDMAN, Administrative Patent Judges.

PRATS, Administrative Patent Judge.

DECISION ON APPEAL
This appeal2 under 35 U.S.C. § 134 involves claims to a process for
providing analgesia in a subject. The Examiner entered a single rejection for
obviousness.

1 Durect Corporation is the real party in interest. Br. 3 (Appeal Brief entered
February 2, 2011).
2 This Appeal is related to Appeal No. 2010-009318, Application No.
10/922,239, now abandoned.
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We have jurisdiction under 35 U.S.C. § 6(b). We affirm the
Examiner’s rejection as to all but one claim.
STATEMENT OF THE CASE
The Specification explains that “there is a great need for devices and
methods for effective and practical management of pain, particularly pain of
long duration, with better efficacy and reduced side effects.” Spec. 4. The
Specification describes addressing that need by implanting into patients a
drug delivery device that contains a pain-ameliorating drug. Id. at 5. A
preferred drug is sufentanil, which is said to be 4,521 times more potent than
morphine. Id. at 16.
Claims 48–56, 58–67, 69–72, 74–81, and 83–91 stand rejected and
appealed. Br. 3. Claims 48, 63, and 84, the independent claims on appeal,
illustrate the appealed subject matter and read as follows (paragraphing
added):
48. A method for providing analgesia in a subject, said method
comprising systemically administering a composition comprising
sufentanil to the subject,
wherein the sufentanil is present in the composition at a
concentration of about 0.5 mg/ml to about 500 mg/ml, and
further wherein the composition is administered to the subject
using an implantable convective delivery system, is delivered from the
system for 48 hours or more at a low volume rate of from about
0.01 µl/day to about 2 ml/day and is sufficient to provide analgesia in
the subject.

63. A method for providing analgesia in a subject, said method
comprising systemically administering to the subject a composition
comprising sufentanil,
wherein said sufentanil is present in the composition at a
concentration of about 0.5 mg/ml to about 500 mg/ml, and
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further wherein the composition is administered to the subject
using an implantable convective delivery system, is delivered from the
system at a low volume rate of from about 0.01 µl/day to about 2
ml/day and is sufficient to provide analgesia in the subject.

84. A method for providing analgesia in a subject, said method
comprising systemically administering to the subject a composition
comprising sufentanil,
wherein the composition is administered to the subject using an
implantable convective delivery system, the composition is delivered
from the system for 48 hours or more at a low volume rate from about
0.1 µl/day to about 2ml/day and is sufficient to deliver from about
0.01 µg/hour to about 200 µg/hour of the sufentanil to the subject,
and further wherein said amount of delivered sufentanil is
sufficient to establish a systemic analgesic effect in the subject.

The only rejection before us for review is the Examiner’s rejection of
claims 48–56, 58–67, 69–72, 74–81, and 83–91 under 35 U.S.C. § 103(a) as
obvious over Wappler,3 Wagemans,4 Peterson,5 and Nelson.6 Ans. 5–10.

3 F. Wappler et al., Analgesia and sedation with sufentanil in intensive care
medicine, 33 ANASTHESIOL. INTENSIVMED. NOTFALLMED. SCHMERZTHER.
18–26 (1998) (as translated). Because the translation does not include page
numbering, we cite to the first page as page 1, and the remaining pages as if
numbered consecutively.
4 Michel F.M. Wagemans et al., Long-Term Spinal Opioid Therapy in
Terminally Ill Cancer Pain Patients, 2 THE ONCOLOGIST 70–75 (1997).
5 Peterson et al., U.S. Patent No. 6,524,305 B1, issued Feb. 25, 2003 (filed
Jul. 24, 1998).
6 Nelson et al., U.S. Patent No. 5,980,927, issued Nov. 9, 1999 (filed Jan. 2,
1997).
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OBVIOUSNESS
The Examiner’s Findings and Prima Facie Case
The Examiner found that Wappler described a process of providing
analgesia in patients by administering sufentanil at a daily dosage
encompassed by the rejected claims. Ans. 6–7. The Examiner found that
Wappler differed from the rejected claims in that it did not teach delivery of
sufentanil using implantable convective devices that deliver from 0.01
µl/day to 2 ml/day, to provide analgesia for prolonged periods. Id. at 7.
To address those deficiencies, the Examiner cited Wagemans as
providing analgesia through long-term sufentanil administration, including
by implanted infusion pump, for months or years. Id. The Examiner also
cited Nelson as describing prolonged delivery of sufentanil by an implanted
device for an extended period lasting up to one year. Id. at 8. The Examiner
cited Table 1 of Nelson as evidence that an ordinary artisan would have
known that the concentration of pain-ameliorating drug in the drug-
containing composition, to be loaded into the implantable device for long
period administration (such as a six month dose), could be calculated if the
daily dose was known. Id.
The Examiner cited Peterson as evidence that the implantable
convective delivery system required by the rejected claims was known in the
art, was suitable for delivery of analgesics, was capable of providing a flow
of beneficial agent between 0.02 to 50 µl/day, and was described as
delivering such agents for as long as a year. Id.
Based on the references’ teachings, the Examiner reasoned that an
ordinary artisan would have considered it obvious to deliver sufentanil at the
dosage rate described in Wappler, using an implantable pump for prolonged
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periods lasting “up to years” as taught by Wagemans. Id. at 9. The
Examiner reasoned further that an ordinary artisan would have been
prompted to use Peterson’s pump to deliver the sufentanil, based on
Peterson’s description of the advantages of its pump, and Peterson’s
teaching that its pump was suitable for delivering analgesics at a low rate for
extended periods. Id. Additionally, the Examiner reasoned, as disclosed by
Nelson, an ordinary artisan would have been able to calculate the
concentration of sufentanil in the sufentanil-containing composition to be
loaded into the device, if the daily dose and period of administration were
known. Id. at 10.
Analysis
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.

Appellants present separate arguments directed to nineteen different
groups of claims. Br. 6–7. For the reasons discussed below, with the
exception of claim 67, Appellants do not persuade us that a preponderance
of the evidence fails to support the Examiner’s prima facie case of
obviousness.
Group 1 (Claims 48–52 and 58)
Appellants contend that, even assuming the Examiner correctly
calculated from Wappler the daily rate of sufentanil administration sufficient
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to achieve analgesia,7 the Examiner, nonetheless, failed to establish that the
cited combination of references teaches a composition in which sufentanil is
present at a concentration of about 0.5 mg/ml to about 500 mg/ml, as claim
48 requires. Br. 8–9. In particular, Appellants contend, because “there are
countless theoretical combinations of concentration and volume per time that
yield identical mass per time dosages,” the mass per time delivery rate
allegedly taught in Wappler “is not suggestive of the concentration of the
solution delivered.” Id. at 9.
The Examiner responds:
Knowing how many mg sufentanil are needed per day as drawn
from the teaching of Wappler and how many ml can be infused
per day from the infusion pump as drawn from Peterson, one
versed in the art would have been able to formulate the
concentration of the sufentanil in the infusion pump. One
having ordinary skill in the art would have been [sic] readily
optimized effective dosages and concurrent administration
regimens of sufentanil as determined by good medical practice
and the clinical condition of the individual patient.

Ans. 13 (emphasis removed).
We find that the preponderance of the evidence supports the
Examiner’s position.
It is well settled that “where the general conditions of a claim are
disclosed in the prior art, it is not inventive to discover the optimum or
workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456

7 Appellants state that they, “in no way acknowledge that Wappler in fact
teaches” a sufentanil delivery rate of 98 to 3600 µg/day, as the Examiner
found. Br. 9, n.1. Appellants do not, however, explain why the Examiner’s
finding is erroneous. Nor do Appellants direct us to any evidence suggesting
that the Examiner’s finding was incorrect.
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(CCPA 1955); see also Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1368
(Fed. Cir. 2007) (“[T]he discovery of an optimum value of a variable in a
known process is usually obvious.”).
In the instant case, claim 48 recites a method for providing analgesia
by systemically administering a sufentanil-containing composition to a
subject. The sufentanil-containing composition must be administered using
an implantable convective delivery system for 48 hours or more. The
delivery system must deliver the sufentanil-containing composition at a
delivery rate of 0.01 µl/day to about 2 ml/day.
Claim 48 also requires the sufentanil-containing composition to
contain sufentanil at a concentration of about 0.5 mg/ml to about 500 mg/ml.
Claim 48, thus, encompasses the use of an implantable delivery system in
which the sufentanil-containing composition loaded into the device contains
sufentanil at a concentration of about 0.5 mg/ml to about 500 mg/ml.
As the Examiner pointed out, Wappler describes providing analgesia
to patients by administering sufentanil. Wappler, 1, 5, 10. We acknowledge
that Wappler does not appear to expressly disclose administering a
sufentanil-containing composition having the sufentanil concentration
required by claim 48.
As the Examiner pointed out, however, Wagemans teaches the
suitability of providing long term analgesia by administering sufentanil
using an implantable device, as claim 48 requires. See Wagemans, 70 (“In
terminally ill cancer patients with refractory pain, long-term spinal opioid
therapy may provide a profound analgesia with minimal side effects. . . .
For epidural administration, it is preferable to use lipid soluble opioids
(sufentanil).”); id. at 73 (“A totally implanted catheter and infusion pump is
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reserved for patients with a life expectancy of months or years. Its reservoir
is refilled percutaneously every 14 to 21 days and provides a constant
infusion rate.”).
As the Examiner pointed out, Nelson also teaches the suitability of
using an implantable device to administer sufentanil for providing long-term
analgesia to patients:
The invention comprises an analgesic carrying device and its
method of use, including implantation, which releases the
analgesic in a continuous and sustained-release manner. . . .
Ideally, therapeutic levels of the analgesic will be delivered
over the long term, i.e., one month to one year. Two preferred
analgesics are fentanyl and sufentanil, opioids about 100 to 500
and 1000 to 5000 times, respectively, more potent than
morphine.

Nelson, col. 2, ll. 30–43. As the Examiner pointed out also, Table 1 of
Nelson illustrates that practitioners must take account of the device’s drug
reservoir size, as well as the concentration of drug in the drug-containing
composition, when preparing an implantable device suitable for providing
analgesia for a particular period of time. Id. at col. 6, ll. 27–50.
As the Examiner pointed out, Peterson teaches that a convective
device, undisputedly encompassed by the rejected claims, was suitable for
long-term administration of analgesics (Peterson, col. 13, ll. 53–65), and was
capable of delivering therapeutic agent at a delivery rate of 0.02 to 50 µl per
day (id. at col. 11, ll. 16–22), a delivery rate within claim 48’s range of
about 0.01 µl/day to about 2 ml/day.
Given the references’ teachings, we agree with the Examiner that an
ordinary artisan, prompted by Wagemans and Nelson to provide long-term
analgesia by administering sufentanil using an implantable device, would
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have considered it obvious, knowing the size and drug delivery rate of the
device, to determine the suitable range of concentrations of sufentanil for the
sufentanil-containing composition to be loaded into an implantable device
such as that described by Peterson.
We acknowledge, as Appellants argue (Br. 9–10), that Wappler does
not appear to expressly describe the volumetric delivery rate of sufentanil
administered to its patients. As our reviewing court has explained, however,
“[n]on-obviousness cannot be established by attacking references
individually where the rejection is based upon the teachings of a
combination of references. . . . [The reference] must be read, not in
isolation, but for what it fairly teaches in combination with the prior art as a
whole.” In re Merck & Co., Inc., 800 F.2d 1091, 1097 (Fed. Cir. 1986).
Thus, in the instant case, even assuming, for the sake of argument,
that Wappler in fact administered a sufentanil-containing composition with a
sufentanil concentration outside the claimed range, the Examiner did not rely
solely on Wappler in rejecting claim 48. Rather, as discussed above, the
Examiner relied also on the teachings of Wagemans and Nelson to show the
desirability of long-term sufentanil administration via an implantable device
and reasoned that an ordinary artisan would have considered it obvious to
determine suitable concentrations of sufentanil for use in the sufentanil-
containing composition to be loaded into that device.
We acknowledge, as Appellants argue (Br. 10–11), that Table 1 of
Nelson is directed to optimizing the parameters of an implantable device for
delivery of fentanyl, rather than the sufentanil recited in claim 48. See
Nelson, col. 6, ll. 27–50. As noted above, however, the potency of
sufentanil was known. See id. at col. 2, ll. 40–43. We agree with the
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Examiner, therefore, that knowing the potency of sufentanil, as well as the
size and delivery rate of a suitable implantable device, an ordinary artisan
would have been prompted by the cited references to determine suitable
concentrations of sufentanil for use in the sufentanil-containing composition
to be loaded into the implantable device. As the Supreme Court has advised,
“[a] person of ordinary skill is also a person of ordinary creativity, not an
automaton.” KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 421 (2007).
Appellants also do not persuade us (see Br. 12–13), that because
Wagemans describes direct administration to the spinal cord, an ordinary
artisan would not have been motivated to combine Wagemans with Wappler,
which like claim 48, describes systemic administration of sufentanil. As
discussed above, the Examiner relied on Wappler as teaching the desirability
of using sufentanil to provide analgesia and Wagemans to show that one
desirable technique of providing long-term analgesia with sufentanil was via
an implantable device. Accordingly, we are not persuaded that the
references are improperly combined.
We acknowledge Wagemans’ teaching, noted above, that when using
sufentanil to provide analgesia, epidural administration is a desirable mode
of administration. Wagemans, 70. We are not persuaded, however, that
claim 48 excludes Wagemans’ epidural administration.
Specifically, claim 48 requires “systemically administering” a
sufentanil-containing composition. Br. 34. The Specification explains that
“[t]he term ‘systemic delivery’ is meant to encompass all parenteral routes
of delivery which permit drug to enter into the systemic circulation, e.g.,
intravenous, intra-arterial, intramuscular, subcutaneous, intra-adipose tissue,
intra-lymphatic, etc.” Spec. 11 (emphasis added). Claim 48, therefore,
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encompasses any non-digestive tract mode of administration that allows
sufentanil to enter into the systemic circulation.
As the Examiner points out (Ans. 7), Wagemans discloses expressly
that epidural administration results in systemic absorption of sufentanil to an
extent similar to that obtained by intramuscular injection, one of the
systemic administration techniques expressly endorsed by Appellants’
Specification. See Wagemans, 72 (“Epidural opioid administration reaches
the receptor in two ways: systemic absorption and penetration of dura mater
and arachnoid. Plasma opioid concentrations after epidural administration
are similar to plasma opioid concentrations after intramuscular injections
when using lipophilic agents such as sufentanil.”). Accordingly, we are not
persuaded that claim 48 excludes the epidural administration taught in
Wagemans. Moreover, because Wagemans expressly teaches the
desirability of epidural sufentanil administration (see, e.g., id. at 70), we are
not persuaded that an ordinary artisan would have viewed the systemic
absorption that accompanied epidural administration as a negative effect of
delivering the drug epidurally.
We are also not persuaded that, because Nelson describes direct
administration of sufentanil to the spine, Nelson teaches away from the
claimed invention, as Appellants argue. Br. 13–15. We acknowledge
Nelson’s teaching that, when providing long-term analgesia by
administering sufentanil via an implantable device, epidural administration
may be used. See Nelson, col. 2, ll. 43–46 (“Preferably the method of the
invention administers the analgesic intraventicularly, intrathecally,
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epidurally, or by other related routes to the neuraxis.”) (emphasis added).8
As noted above, Wagemans teaches that epidural administration of
sufentanil results in systemic delivery of the drug to a degree similar to that
of intramuscular injection, one of the systemic delivery techniques expressly
endorsed by Appellants’ Specification. Accordingly, because Nelson’s
epidural administration results in systemic circulation of sufentanil, and
because claim 48 encompasses any non-digestive tract mode of
administration that allows systemic circulation of sufentanil, we are not
persuaded that Nelson’s teaching of epidural administration equates to a
teaching away from the claimed invention.
In sum, for the reasons discussed, Appellants’ arguments do not
persuade us that the preponderance of the evidence fails to support the
Examiner’s prima facie case of obviousness as to claim 48. Because
Appellants presented no clear or specific objective evidence of non-
obviousness to rebut the Examiner’s prima facie case, we affirm the
Examiner’s rejection of claim 48. Because claims 49–52 and 58 were
argued in the same claim grouping, they fall with claim 48. See 37 C.F.R.
§ 41.37(c)(1)(vii).
Group 2 (Claim 53)
Claim 53 depends from claim 48 through claim 49, and recites “[the
method of claim 48, wherein the composition is delivered using a patterned
delivery regime, and] wherein the composition is delivered over an extended
period of time.” Br. 34. Appellants’ Specification explains that a patterned

8 Nelson explains that the term “neuraxis” means “any region of tissue that
comprises the spinal cord, brain or central nervous system.” Nelson, col. 1,
ll. 21–22.
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delivery regime can be substantially continuous delivery (Spec. 12), and that
an extended period of time can be from several hours to several years (id. at
23).
Appellants contend that the Examiner has not adequately explained
how the cited references teach or suggest the highly concentrated sufentanil-
containing composition required by claim 53, particularly given the use in
the prior art of sufentanil compositions with concentrations lower than
required by claim 53. Br. 16–18. Appellants contend that the Examiner has
not provided evidence that a composition having the high concentration of
sufentanil required by claim 53 was in the prior art. Id. at 16.
We are not persuaded. As is evident from its language, claim 53 does
not contain any express limitation regarding the sufentanil concentration in
the claimed sufentanil-containing composition, beyond the requirements of
claim 48 discussed above. Accordingly, Appellants’ arguments, that claim
53 requires a sufentanil-containing composition of high concentration, are
not directed to a limitation actually present in the claim at issue. As
discussed above, moreover, Peterson teaches that an implantable device,
expressly described as being suitable for administering an analgesic,
provides a delivery rate encompassed by the claims.
We acknowledge that certain prior art sufentanil-containing
compositions cited by Appellants may have contained sufentanil at
concentrations lower than the concentration range required by claim 53
through its dependency from 48, and that certain prior art may have
suggested administering relatively high volumes of those compositions. See
Br. 16–17. Those facts do not, however, demonstrate error in the
Examiner’s finding that an ordinary artisan, prompted by Wagemans and
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Nelson to prepare sufentanil-containing compositions suitable for loading
into a device such as that described in Peterson, had a reasonable expectation
of preparing a composition with a sufentanil concentration within the
claimed range. As to commercially available sufentanil compositions (Br.
17), our reviewing court has explained that “[n]othing in the statute or our
case law requires [the proponent] to prove obviousness by starting with a
prior art commercial embodiment and then providing motivation to alter that
commercial embodiment.” Galderma Labs., L.P. v. Tolmar, Inc., 737 F.3d
731, 737 (Fed. Cir. 2013).
As to Appellants’ contentions that their Specification describes
preparing sufentanil-containing compositions with high sufentanil
concentrations providing exceptional benefit to the art (Br. 17–18), it is well
settled that it is improper to import limitations into the claims from preferred
embodiments in the Specification. In re Trans Texas Holdings Corp., 498
F.3d 1290, 1299 (Fed. Cir. 2007). Appellants, moreover, direct us to no
clear or specific evidence suggesting that a sufentanil-containing
composition having sufentanil in the concentration range required by claim
53 possessed any unexpected properties.
In sum, because Appellants’ arguments do not persuade us, for the
reasons discussed, that the preponderance of the evidence fails to support the
Examiner’s prima facie case of obviousness as to claim 53, we affirm the
Examiner’s rejection of that claim.
Group 3 (Claim 54)
Claim 54 recites “[t]he method of claim 53, wherein the composition
is delivered for a period of about 72 hours.” Br. 34.
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Similar to claim 53, Appellants contend that the Examiner has not
adequately explained how the cited references teach or suggest the highly
concentrated sufentanil-containing composition required by claim 54, nor
has the Examiner provided evidence that a composition having the high
concentration of sufentanil required by claim 54 was in the prior art. Br. 19.
Appellants contend that the prior art suggested administering high volumes
of sufentanil-containing compositions which would not have been suitable
for loading into implantable devices. Id.
We are not persuaded. Claim 54 does not contain any express
limitation regarding the sufentanil concentration in the claimed sufentanil-
containing composition beyond the requirements of claim 48 discussed
above. Appellants’ arguments, that claim 54 requires a sufentanil-containing
composition of high concentration, are therefore not directed to a limitation
actually present in the claim at issue.
Moreover, for the reasons discussed above, we are not persuaded that
the Examiner has failed to show that an ordinary artisan, prompted by
Wagemans and Nelson to provide long-term analgesia by administering a
sufentanil-containing composition via an implantable device such as that
described in Peterson, would have considered it obvious to determine the
suitable sufentanil concentration for the composition to be loaded into the
device. Accordingly, we affirm the Examiner’s rejection of claim 54.
Group 4 (Claim 55)
Claim 55 recites “[t]he method of claim 53, wherein the composition
is delivered for a period from 2 to 5 days.” Br. 34.
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Appellants contend that their arguments discussed above as to Groups
1 and 2 “apply with at least equal force, if not greater force, to the rejection
of Claim 55.” Br. 19.
For the reasons discussed above, we do not find Appellants’
arguments persuasive. Accordingly, we affirm the Examiner’s rejection of
claim 55.
Group 5 (Claim 56)
Claim 56 recites “[t]he method of claim 53, wherein the composition
is delivered for a period of at least 100 days.” Br. 35.
Appellants contend that their arguments discussed above as to Groups
1 and 2 “apply with at least equal force, if not greater force, to the rejection
of Claim 56.” Br. 20. Appellants note that the duration of sufentanil
delivery required by claim 56 is longer than that recited in each of claims 54
and 55. Id.
For the reasons discussed above, we do not find Appellants’
arguments persuasive. In particular, we note, as the Examiner pointed out,
that Nelson teaches the desirability using an implantable device to deliver
sufentanil for a period of up to a year (Nelson, col. 2, ll. 25–47), and that
Peterson’s calculations for its device similarly suggest a contemplated use
for up to a year (Peterson, Table 1). Because we do not find Appellants’
arguments persuasive, we affirm the Examiner’s rejection of claim 56.
Group 6 (Claim 59)
Claim 59 recites “[t]he method of claim 48, wherein the composition
is delivered to the subject at a volume rate of from about 0.01 µl/day to
about 100 µl/day.” Br. 35.
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Appellants contend that the cited combination of references fails to
teach or suggest a delivery system capable of delivering the volume rate
required by claim 59. Br. 20.
As the Examiner pointed out, however, Peterson teaches that a
convective device, undisputedly encompassed by the rejected claims, was
suitable for administration of analgesics (Peterson, col. 13, ll. 53–65) and
was capable of delivering therapeutic agent at a delivery rate of 0.02 to 50 µl
per day (id. at col. 11, ll. 16–22), which is a delivery rate within claim 59’s
range of about 0.01 µl/day to about 100 µl/day.
Appellants contend that the Examiner has not adequately explained
how the cited references teach or suggest the highly concentrated sufentanil-
containing composition required by claim 59, that the Examiner has not
provided evidence that a composition having the high concentration of
sufentanil required by claim 59 was in the prior art, and that the prior art
suggested administering high volumes of sufentanil-containing
compositions. Therefore, Appellants contend that the prior art would not
have provided a reasonable expectation of providing analgesia using the low
volume delivery rate claimed. Br. 20–21.
We are not persuaded. Claim 59 does not contain any express
limitation regarding the sufentanil concentration in the claimed sufentanil-
containing composition, beyond the requirements of claim 48 discussed
above. As to the sufentanil concentration in the sufentanil-containing
composition to be loaded into the claimed implantable device, for the
reasons discussed above, we agree with the Examiner that an ordinary
artisan, prompted by Wagemans and Nelson to provide long-term analgesia
by administering a sufentanil-containing composition via an implantable
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device such as that described in Peterson, would have considered it obvious
to determine the suitable sufentanil concentration for the composition to be
loaded into the device.
Accordingly, because we do not find Appellants’ arguments
persuasive, we affirm the Examiner’s rejection of claim 59.
Group 7 (Claim 60)
Claim 60 recites “[t]he method of claim 48, wherein the composition
is delivered to the subject at a volume rate of from about 0.04 µl/day to
about 10 µl/day.” Br. 35.
Appellants contend that the arguments directed to claim 59 discussed
above, “apply with at least equal force, if not greater force, to the rejection
of Claim 60 because the high end of the volume range in Claim 60 is lower
than that recited in Claim 59.” Br. 21. Appellants contend that the cited
references do not teach or suggest the highly concentrated sufentanil-
containing composition required by claim 60. Id. at 21–22.
As noted above, however, Peterson teaches that a convective device
suitable for administration of analgesics was capable of delivering a
therapeutic agent at a delivery rate of 0.02 to 50 µl per day (Peterson, col.
11, ll. 16–22), a delivery rate entirely overlapping claim 60’s range of about
0.04 µl/day to about 10 µl/day. As to the sufentanil concentration in the
sufentanil-containing composition to be loaded into the claimed implantable
device, for the reasons discussed above, we do not find Appellants’
arguments persuasive.
Accordingly, because we do not find Appellants’ arguments
persuasive, we affirm the Examiner’s rejection of claim 60.
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Group 8 (Claim 61)
Claim 61 recites “[t]he method of claim 48, wherein the composition
is delivered to the subject at a volume rate of from about 0.2 µl/day to about
5 µl/day.” Br. 35.
Appellants contend that the arguments directed to claim 60 discussed
above, “apply with at least equal force, if not greater force, to the rejection
of Claim 61 because the high end of the volume range in Claim 61 (5
µl/day) is lower than that recited in Claim 60 (10 µl/day).” Br. 22.
Appellants contend that the cited references do not teach or suggest the
highly concentrated sufentanil-containing composition required by claim 61.
Id. at 21–22.
As noted above, however, Peterson teaches that a convective device
suitable for administration of analgesics was capable of delivering a
therapeutic agent at a delivery rate of 0.02 to 50 µl per day (Peterson, col.
11, ll. 16–22), a delivery rate entirely overlapping claim 61’s range of about
0.2 µl/day to about 5 µl/day. As to the sufentanil concentration in the
sufentanil-containing composition to be loaded into the claimed implantable
device, for the reasons discussed above, we do not find Appellants’
arguments persuasive.
Accordingly, because we do not find Appellants’ arguments
persuasive, we affirm the Examiner’s rejection of claim 61.
Group 9 (Claim 62)
Claim 62 recites “[t]he method of claim 48, wherein the composition
is delivered to the subject at a volume rate of from about 0.5 µl/day to about
1 µl/day.” Br. 35.
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Appellants contend that the arguments directed to claim 61 discussed
above, “apply with at least equal force, if not greater force, to the rejection
of Claim 62 because the high end of the volume range in Claim 62 (1µl/day)
is lower than that recited in Claim 61 (5 µl/day).” Br. 23. Appellants
contend that the cited references do not teach or suggest the highly
concentrated sufentanil-containing composition required by claim 62. Id.
As noted above, however, Peterson teaches that a convective device
suitable for administration of analgesics was capable of delivering a
therapeutic agent at a delivery rate of 0.02 to 50 µl per day (Peterson, col.
11, ll. 16–22), a delivery rate entirely overlapping claim 62’s range of about
0.5 µl/day to about 1 µl/day. As to the sufentanil concentration in the
sufentanil-containing composition to be loaded into the claimed implantable
device, for the reasons discussed above, we do not find Appellants’
arguments persuasive.
Accordingly, because we do not find Appellants’ arguments
persuasive, we affirm the Examiner’s rejection of claim 62.
Group 10 (Claims 63–66, 74–77, 79, and 83)
As seen above, claim 63 recites substantially the same process as
recited in claim 48, except that claim 63 does not require delivery of the
sufentanil-containing composition for 48 hours or more. Appellants contend
that the Examiner failed to demonstrate that the process recited in claim 63
would have been obvious to an ordinary artisan, for substantially the same
reasons discussed above as to claim 48 (Group 1). Id. at 23–25.
For the reasons discussed above as to claim 48, we do not find
Appellants’ arguments persuasive as to claim 63. Accordingly, we affirm
the Examiner’s rejection of claim 63. Because claims 64–66, 74–77, 79, and
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83, were argued in the same claim grouping, they fall with claim 63. See 37
C.F.R. § 41.37(c)(1)(vii).
Group 11 (Claim 67)
Claim 67 recites “[t]he method of claim 63, wherein the sufentanil is
present in the composition at a concentration of about 2 to about 10,000
times greater than the solubility of sufentanil in aqueous solution.” Br. 36.
Appellants contend that given the low concentrations of sufentanil in
prior art aqueous formulations of the drug, an ordinary artisan would not
have had a reasonable expectation of preparing a sufentanil formulation
having the concentration required by claim 67. Br. 25–26.
The Examiner responds as follows:
Knowing how many mg sufentanil are needed per day as drawn
from the teaching of Wappler and how many ml can be infused
per day from the infusion pump as drawn from Peterson, one
versed in the art would have been able to formulate the
concentration of the sufentanil in the infusion pump. One
having ordinary skill in the art would have been readily
optimized effective dosages and concurrent administration
regimens of sufentanil as determined by good medical practice
and the clinical condition of the individual patient.
Determination of the appropriate dosage for treatment involving
sufentanil to provide analgesia would have been routinely made
by those of ordinary skill in the art and is within the ability of
tasks routinely performed by them without undue
experimentation, especially in light of the dosage information
disclosed prior art and depending on variety of factors including
the severity of the condition to be treated, the desired effect,
possible of adverse reaction, and individual patient including
age, sex, body weight, etc.

Ans. 32–33 (emphasis removed).
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In this instance, we find that Appellants have the better position. As
discussed above, we agree with the Examiner that an ordinary artisan would
have considered it obvious to determine the range of suitable concentrations
of sufentanil to use in a sufentanil-containing composition to be loaded into
an implantable device.
The Examiner has not, however, directed us to any non-aqueous
sufentanil-containing compositions anywhere in the record. Nor has the
Examiner explained with any specificity how a composition having the
sufentanil concentration required by claim 67 would be prepared.
Accordingly, because we are not persuaded that the Examiner has explained
adequately how or why an ordinary artisan would have prepared a
sufentanil-containing composition having the sufentanil concentration
required by claim 67, we reverse the Examiner’s rejection of claim 67.
Group 12 (Claim 69)
Claim 69 recites “[t]he method of claim 63, wherein the sufentanil is
present in the composition at a concentration of from about 1 mg/ml to about
400 mg/ml.” Br. 36.
Appellants contend that the arguments discussed above as to claim 63
“apply with at least equal force, if not greater force, to the rejection of Claim
69 because the low end of the concentration range in Claim 69 is higher than
that recited in Claim 63.” Id. at 26.
We are not persuaded. Rather, for the reasons discussed above, we
agree with the Examiner that an ordinary artisan, prompted by Wagemans
and Nelson to provide long-term analgesia by administering a sufentanil-
containing composition via an implantable device such as that described in
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Peterson, would have considered it obvious to determine the suitable
sufentanil concentration for the composition to be loaded into the device.
Accordingly, because we do not find Appellants’ arguments
persuasive, we affirm the Examiner’s rejection of claim 69.
Group 13 (Claim 70)
Claim 70 recites “[t]he method of claim 63, wherein the sufentanil is
present in the composition at a concentration of from about 50 mg/ml to
about 400 mg/ml.” Br. 36.
Appellants contend that the arguments discussed above as to claim 69
“apply with at least equal force, if not greater force, to the rejection of Claim
70 because the low end of the concentration range in Claim 70 is higher than
that recited in Claim 69.” Id. at 27.
We are not persuaded. Rather, for the reasons discussed above, we
agree with the Examiner that an ordinary artisan, prompted by Wagemans
and Nelson to provide long-term analgesia by administering a sufentanil-
containing composition via an implantable device such as that described in
Peterson, would have considered it obvious to determine the suitable
sufentanil concentration for the composition to be loaded into the device.
Accordingly, because we do not find Appellants’ arguments
persuasive, we affirm the Examiner’s rejection of claim 70.
Group 14 (Claim 71)
Claim 71 recites “[t]he method of claim 63, wherein the sufentanil is
present in the composition at a concentration of from about 75 mg/ml to
about 300 mg/ml.” Br. 36.
Appellants contend that the arguments discussed above as to claim 70
“apply with at least equal force, if not greater force, to the rejection of Claim
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71 because the low end of the concentration range in Claim 70 is higher than
that recited in Claim 70.” Id. at 27.
We are not persuaded. Rather, for the reasons discussed above, we
agree with the Examiner that an ordinary artisan, prompted by Wagemans
and Nelson to provide long-term analgesia by administering a sufentanil-
containing composition via an implantable device, such as that described in
Peterson, would have considered it obvious to determine the suitable
sufentanil concentration for the composition to be loaded into the device.
Appellants contend that, “because Nelson teaches delivery directly to
the drug’s site of action, a person of ordinary skill in the art would be
directed away from the use of the highly concentrated formulation of the
instant claim.” Id. at 27. Appellants contend that “[d]elivery of such a
formulation directly to the site of drug action, e.g., via implantation in a
brain ventricle, would be associated with a high risk of negative side
effects.” Id. at 27–28.
Appellants do not, however, direct us to any clear or specific evidence
supporting their assertion that administration of a composition having the
claimed sufentantil concentration would have been expected to result in
negative side effects at a delivery rate encompassed by the claims. It is well
settled that attorney argument is not an adequate substitute for actual
evidence. In re Geisler, 116 F.3d 1465, 1471 (Fed. Cir. 1997).
Accordingly, because we do not find Appellants’ arguments
persuasive, we affirm the Examiner’s rejection of claim 71.
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Group 15 (Claim 72)
Claim 72 recites “[t]he method of claim 63, wherein the sufentanil is
present in the composition at a concentration of from about 100 mg/ml to
about 250 mg/ml.” Br. 36.
Appellants contend that the arguments discussed above as to claim 71
“apply with at least equal force, if not greater force, to the rejection of Claim
72 because the low end of the concentration range in Claim 70 is higher than
that recited in Claim 71.” Id. at 27.
We are not persuaded. Rather, for the reasons discussed above, we
agree with the Examiner that an ordinary artisan, prompted by Wagemans
and Nelson to provide long-term analgesia by administering a sufentanil-
containing composition via an implantable device such as that described in
Peterson, would have considered it obvious to determine the suitable
sufentanil concentration for the composition to be loaded into the device.
As to Appellants’ contention that Nelson’s delivery directly to the
drug’s site of action would have directed an ordinary artisan away from the
claimed process because of expected negative side effects, as discussed
above, Appellants do not direct us to any clear or specific evidence, outside
of argument by counsel, supporting the alleged prior art expectation of
negative side effects.
Accordingly, because we do not find Appellants’ arguments
persuasive, we affirm the Examiner’s rejection of claim 72.
Group 16 (Claim 78)
Claim 78 depends from claim 63 through claim 74, and recites “[the
method of claim 63, wherein the composition is delivered using a patterned
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delivery regime, and] wherein the composition is delivered over an extended
period of time.” Br. 36–37.
Appellants contend that claim 78 includes the same limitations as
claim 53, discussed above, and contend, therefore, that the Examiner failed
to establish a prima facie case of obviousness as to claim 78, based on the
same arguments discussed above as to claim 53. Id. at 29.
For the reasons discussed above as to claim 53, we do not find
Appellants’ arguments persuasive. Accordingly, we affirm the Examiner’s
rejection of claim 78.
Group 17 (Claim 80)
Claim 80 recites “[t]he method of claim 78, wherein the composition
is delivered for a period from 2 to 5 days.” Br. 34.
Appellants contend that their arguments discussed above as to claim
78 “apply with at least equal force” to the rejection of claim 80. Id. at 29.
For the reasons discussed above, we do not find Appellants’
arguments persuasive. Accordingly, we affirm the Examiner’s rejection of
claim 80.
Group 18 (Claim 81)
Claim 81 recites “[t]he method of claim 78, wherein the composition
is delivered for a period of at least 100 days.” Br. 37.
Appellants contend that their arguments discussed above as to claim
80 “apply with at least equal force, if not greater force, to the rejection of
Claim 81.” Id. at 30. Appellants note that the duration of sufentanil delivery
required by claim 81 is longer than that recited in claim 80. Id.
For the reasons discussed above, we do not find Appellants’
arguments persuasive. In particular, we note, as the Examiner pointed out,
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that Nelson teaches the desirability of using an implantable device to deliver
sufentanil for a period of up to a year (Nelson, col. 2, ll. 25–47) and that
Peterson’s calculations for its device similarly suggest a contemplated use
for up to a year (Peterson, Table 1).
Accordingly, because we do not find Appellants’ arguments
persuasive, we affirm the Examiner’s rejection of claim 81.
Group 19 (Claims 84–91)
As seen above, claim 84 recites a process similar to that recited in
claim 48, except that, in addition to requiring delivery of a sufentanil-
containing composition to a subject at a delivery rate of 0.1 µl/day to about
2ml/day, the delivery rate must also be sufficient to deliver from about 0.01
µg/hour to about 200 µg/hour sufentanil to the subject. See Br. 37. Claim
84 does not, however, expressly limit the sufentanil-containing composition
to any particular sufentanil concentration. See id.
Appellants contend that their arguments regarding claim 48 “with
respect to teaching away and the lack of an apparent reason to combine the
references, apply equally to the rejection of independent Claim 84.” Id. at
31. For the reasons discussed above, as to claim 48, we do not find these
arguments persuasive.
Appellants contend that, “by virtue of the recited delivery rates and
administration periods,” claim 84 requires a “highly concentrated sufentanil
composition.” Id. Appellants also reiterate their contentions that the instant
application discloses sufentanil-containing compositions with sufentanil
concentrations substantially higher than prior art conventional or
commercial formulations, and their contention that an ordinary artisan
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lacked a reasonable expectation of being able to provide analgesia using a
composition having the claimed sufentanil concentration. Id. at 32.
As noted above, however, claim 84 does not expressly limit the
sufentanil-containing composition to any particular sufentanil concentration.
Appellants, moreover, do not explain clearly or specifically how the features
of claim 84 might limit the concentration of the sufentanil-containing
composition delivered to the subject or what the concentration might be.
Nonetheless, to the extent the delivery rates and other features recited
in claim 84 might require the sufentanil-containing composition to have a
particular sufentanil concentration, as discussed above, we agree with the
Examiner that an ordinary artisan, prompted by Wagemans and Nelson to
provide long-term analgesia by administering a sufentanil-containing
composition via an implantable device such as that described in Peterson,
would have considered it obvious to determine the suitable sufentanil
concentration for the composition to be loaded into the device. Further, as to
Appellants’ contention that Nelson’s delivery directly to the drug’s site of
action would have directed an ordinary artisan away from the claimed
process because of expected negative side effects, as discussed above,
Appellants do not direct us to any clear or specific evidence, outside of
argument by counsel, supporting the alleged prior art expectation of negative
side effects.
In sum, for the reasons discussed, we do not find Appellants’
arguments persuasive as to claim 84. Accordingly, we affirm the
Examiner’s rejection of claim 84. Because claims 85–91 were argued in the
same claim grouping, they fall with claim 84. See 37 C.F.R.
§ 41.37(c)(1)(vii).
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SUMMARY
For the reasons discussed, we affirm the Examiner’s obviousness
rejection as to all claims except claim 67.

TIME PERIOD
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-IN-PART
tc