Ex Parte Ishikawa et al

Board of Patent Appeals and Interferences

Jan 17, 2012

11150861 (B.P.A.I. Jan. 17, 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.
11/150,861 06/10/2005 Muriel Y. Ishikawa 17906.20 3487
83722 7590 01/18/2012
Workman Nydegger / INVENTION SCIENCE FUND
1000 EAGLE GATE TOWER
60 EAST SOUTH TEMPLE
SALT LAKE CITY, UT 84111
EXAMINER
DUTT, ADITI
ART UNIT PAPER NUMBER
1649
MAIL DATE DELIVERY MODE
01/18/2012 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 BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte MURIEL Y. ISHIKAWA, EDWARD K.Y. JUNG,
and LOWELL L. WOOD, JR.
__________

Appeal 2011-007753
Application 11/150,861
Technology Center 1600
__________

Before DONALD E. ADAMS, ERIC GRIMES, and FRANCISCO C.
PRATS, Administrative Patent Judges.

Opinion for the Board filed by Administrative Patent Judge GRIMES.

Opinion Dissenting filed by Administrative Patent Judge PRATS.

GRIMES, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to methods
of elevating the concentrations of neurotrophin in neural tissues. The
Examiner has rejected the claims as obvious. We have jurisdiction under 35
U.S.C. § 6(b). We reverse.
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STATEMENT OF THE CASE
The Specification discloses methods “for modulating the
concentration of one or more neurotrophins within or in the vicinity of
neural tissues” by elevating the concentration of either a neurotrophin or an
inhibitor of neurotrophin degradation (Spec. 1). The Specification discloses
that the methods “may find application in conjunction with neural tissue
grafts, implants or related surgical therapies” (id. at 2). The Specification
discloses that “the neurotrophin may be cAMP” and the inhibitor of
degradation may be a phosphodiesterase (id. at 5).
Claims 49, 50, 128-134, 137, 139, 140, 144, 147-156, 159, 164, and
167-170 are on appeal. Claim 49 is representative and reads as follows:
49. A method of elevating, in a highly innervated tissue in a subject,
the concentrations of at least one neurotrophin and at least one inhibitor of
degradation of said neurotrophin, comprising:
(a) introducing into a highly innervated tissue in a subject at least one
neurotrophin to elevate a neurotrophin concentration of the at least one
neurotrophin within the highly innervated tissue;
(b) introducing into the highly innervated tissue at least one inhibitor
of degradation of the at least one neurotrophin to elevate an inhibitor
concentration of the at least one inhibitor of degradation of said neurotrophin
within the highly innervated tissue; and
(c) regulating the concentration of the neurotrophin over time,
wherein regulating includes:
monitoring, with at least one implanted sensor device, the
neurotrophin concentration to determine whether at least one desired
neurotrophin concentration target level of the at least one neurotrophin is
present; and
adding additional neurotrophin in a quantity sufficient to adjust the
neurotrophin concentration toward the at least one desired neurotrophin
concentration target level.

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Similar to claim 49, claims 50 and 170, the only other independent
claims, require monitoring the concentration of an inhibitor of neurotrophin
degradation (claim 50) or monitoring the concentration of both a
neurotrophin and an inhibitor of neurotrophin degradation (claim 170).
The Examiner has rejected claims 49, 50, 128-134, 137, 139, 140,
147-156, 159, and 167-170 under 35 U.S.C. § 103(a) as being obvious in
view of Bunge1 and Gupta.2 The Examiner has also rejected claims 144 and
1643 under 35 U.S.C. § 103(a) as being obvious in view of Bunge, Gupta,
and Lautt.4 Since the same issue is dispositive for both rejections, we will
consider them together.
The Examiner finds that Bunge discloses “the administration of
cAMP … and a phosphodiesterase inhibitor such as rolipram … using
minipumps, or a subcutaneous injection either systemically or at the site of
CNS [central nervous system] injury” (Answer 6). The Examiner also finds
that Bunge discloses “maintaining the administration of the phospho-
diesterase inhibitor and cAMP, by repetitive systemic injections or
continuous administration over longer periods of time, so as to produce a
therapeutic effect” (id.). The Examiner finds that Gupta discloses

1 Bunge et al., Patent Application Publication US 2003/0220280, Nov. 27,
2003
2 AK Gupta, Monitoring the injured brain in the intensive care unit, 48 J.
POSTGRAD. MED. 218-25 (2002)
3 Although Appellants did not list the rejection of claims 144 and 164 as a
ground of rejection to be reviewed on appeal, Appellants’ brief addresses
claims 144 and 164 (Appeal Brief 11). Thus, this appeal also involves the
rejection of claims 144 and 164.
4 Lautt et al., Patent Application Publication US 2003/0181461 A1, Sept. 25,
2003
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“implantable sensor devices … for continuous monitoring of the changes in
the CNS” (id.).
The Examiner concludes that it “would have been obvious to the
person of ordinary skill in the art … to modify [Bunge’s] method for
repetitive systemic and continuous administration of cAMP and
phosphodiesterase inhibitors over long periods … [to include Gupta’s]
method of constant monitoring of changes in various levels within the CNS
tissue using implantable sensor devices … because the implanted devices
can be applied for measuring various drug concentrations.… [T]he sensor
devices also allow the practitioner to take immediate measures for obtaining
the desired effect.” (Id. at 7.)
Appellants argue that the Examiner has not shown that Bunge
inherently discloses monitoring the levels of a neurotrophin, or an inhibitor,
over time (Appeal 13-14) and the Examiner has not provided a reason why
one of ordinary skill in the art would have been motivated to modify Bunge
to include monitoring (id. at 17). Appellants argue that “the Examiner
merely states an alleged capability of [ ] Gupta without providing any reason
from Bunge, Gupta, or knowledge common to one of ordinary skill in the art
why the capability is desirable in view of Bunge” (id.).
The Examiner responds that “Bunge teaches repetitive systemic
injections or continuous administration over longer periods of time, so as to
produce a therapeutic effect or ‘until it is deemed by the skilled practitioner
that further gain of function is unlikely,’” which “implies that Bunge teaches
regulating the concentration over time and monitoring the same” (Answer
14). The Examiner argues that, since Bunge aims to elevate the level of
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cyclic nucleotide cyclase over an extended period of time to achieve a
desired therapeutic effect, “the skilled artisan will realize that the level or
concentration needs to be checked or monitored to observe the elevation or
the desired concentration and the therapeutic effect” (id. at 15). The
Examiner concludes that “even though the word ‘monitoring’ is missing in
the Bunge reference, the reference surely suggests … checking of levels at
variable time points.… Based upon technical reasoning that naturally flows
from the Bunge teachings, no further extrinsic evidence is required to
provide support for inherency.” (Id. at 16.)
We agree with Appellants that the Examiner has not adequately
shown that the cited references would have made obvious the claimed
method because the Examiner erred in finding that Bunge discloses or
suggests monitoring the concentration of therapeutic agents. Bunge
discloses
methods of restoring motor and/or sensory function to an
animal following CNS injury.… [C]ells that provide or mimic
the functions of neural cells … are implanted at the site of CNS
injury and both a cyclic nucleotide phosphodiesterase inhibitor
and a composition that elevates intracellular levels of a cyclic
nucleotide cyclase are administered to the animal.
(Bunge, ¶ 0008.)
Bunge discloses that the “phosphodiesterase inhibitor can be
administered continuously over a long period of time (e.g. hours, days,
weeks or longer) by use of an osmotic minipump [or] by repetitive systemic
injection” (id. at ¶ 0033). Bunge discloses that “rolipram or another
phosphodiesterase inhibitor will be administered continuously … until it is
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deemed by the skilled practitioner that further gain of function is unlikely”
(id. at ¶ 0034 ).
The Examiner asserts that Bunge inherently discloses monitoring the
concentration of the therapeutic agent after administration. However, this
finding is in error because Bunge only discloses monitoring the effects, not
the concentration, of the therapeutic agent. See Bunge ¶ 0033
(“Administration of the phosphodiesterase inhibitor [rolipram] must be
maintained during and after administration of the composition that elevates
intracellular levels of a cyclic nucleotide cyclase”) and ¶ 0034 (“rolipram …
will be administered continuously … until it is deemed by the skilled
practitioner that further gain of function is unlikely”). Although the
Examiner finds that Bunge discloses that “methods of detection or
measuring such compounds can be done using techniques known to a skilled
person in the art (para 0027)” (Answer 15), the methods in the cited
paragraph are for screening compounds for their ability to activate adenylate
or guanylate cyclase (Bunge ¶ 0027), not monitoring levels of a therapeutic
agent in a patient.
The Examiner also argues that, because the goal of Bunge’s method
was to elevate the level of cyclic nucleotide cyclase over an extended period
of time to achieve a therapeutic effect, “the skilled artisan will realize that
the level or concentration needs to be checked or monitored to observe the
elevation or the desired concentration and the therapeutic effect” (Answer
15). The Examiner, however, points to no evidence showing that Bunge’s
method was intended to achieve a specific “desired concentration” of the
administered compounds or of cyclic nucleotide cyclase.
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That is, although Bunge states that its method “elevates intracellular
levels of a cyclic nucleotide cyclase” (Bunge ¶ 0008), the Examiner has not
pointed to any disclosure of a specific level to be achieved, or any other
disclosure that would provide a skilled worker with a reason to carry out the
additional steps required to monitor the level of neurotrophin and/or
inhibitor of neurotrophin degradation, as required by the claims on appeal.
Rather, Bunge directs those skilled in the art to administer the dosages of its
therapeutic agents to the site of injury, and to continue administering the
agents until no further gain of function is likely. The Examiner has not
adequately explained why a skilled worker would have had a reason to
modify this method to include a step of monitoring the level(s) of the
administered compounds.
Because the Examiner erred in finding that Bunge discloses or
suggests monitoring the concentration of the therapeutic agent, we are
compelled to reverse the rejection of independent claims 49, 50, and 170,
and dependent claims 128-134, 137, 139, 140, 147-156, 159, and 167-169.
For the same reason, we also reverse the rejection of claims 144 and 164 in
view of Bunge, Gupta, and Lautt.
SUMMARY
We reverse the rejection of claims 49, 50, 128-134, 137, 139, 140,
144, 147-156, 159, 164, and 167-170 under 35 U.S.C. § 103(a).

REVERSED

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PRATS, Administrative Patent Judge, dissenting.
I respectfully dissent.
While I agree with Appellants and my colleagues that Bunge does not
inherently describe monitoring and regulating the neurotrophin
concentration in a subject, I do not agree that the Examiner has failed to
supply an adequate reason for performing those steps. As acknowledged in
the majority opinion, when responding to Appellants’ arguments, the
Examiner ultimately finds as follows:
Since the Bunge reference aims at elevating the concentration
of cyclic nucleotide cyclase by administration of PDE inhibitor
and cAMP activator concentration over longer periods of time
(hours, days, weeks or longer) to produce the desired
therapeutic effect, the skilled artisan will realize that the level
or concentration needs to be checked or monitored to observe
the elevation or the desired concentration and the therapeutic
effect. . . . [T]he reference surely suggests that the checking of
levels at variable time points would necessarily result in
achieving the desired target level.

(Ans. 15-16.)
Although Appellants argue that this “new reasoning” is inadequate
(Reply Br. 7), given Bunge’s repeated emphasis on maintaining “elevate[d]
intracellular levels of nucleotide cyclases” (Bunge, abstract; see also id. at
[0008], [0033]), I do not agree that the Examiner erred in concluding that an
ordinary artisan would have considered it obvious to monitor a patient’s
intracellular concentration of that therapeutic agent, so as to ensure
therapeutic success.
The fact situation presented here invokes the Supreme Court’s
directives in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 (2007). In KSR, the
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Court rejected a “rigid approach” to the obviousness question, and instead
emphasized that “[t]hroughout this Court’s engagement with the question of
obviousness, our cases have set forth an expansive and flexible approach . . .
.” Id. at 415. The Court also rejected the use of “rigid and mandatory
formulas” as being “incompatible with our precedents.” Id. at 419; see also
421 (“Rigid preventative rules that deny factfinders recourse to common
sense, however, are neither necessary under our case law nor consistent with
it.”).
Rather, the Court advised, in determining whether the prior art
supplied a reason for practicing the claimed subject matter, the analysis
“need not seek out precise teachings directed to the specific subject matter of
the challenged claim, for a court can take account of the inferences and
creative steps that a person of ordinary skill in the art would employ.” Id. at
418; see also id. at 421 (“A person of ordinary skill is . . . a person of
ordinary creativity, not an automaton.”).
Here, given Bunge’s suggestion that one could simply observe the
patient’s outward response to the treatment so as to determine whether to
administer additional therapeutic agent (see Bunge [0034]), it might be true
that Bunge supplies no specific or explicit teaching that would have
prompted an ordinary to monitor the concentration of the agent within the
patient. As KSR explains however, the inquiry does not end there.
Instead, the obviousness inquiry must consider what an ordinary
artisan would have reasonably inferred from the prior art teachings. KSR,
550 U.S. at 418 (“[A] court can take account of the inferences and creative
steps that a person of ordinary skill in the art would employ.”)
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Given Bunge’s disclosure that its method requires elevation of the
level of its therapeutic agent above the normal cellular concentration, I do
not perceive error in the Examiner’s finding, and ultimate conclusion
derived therefrom, that it would have been obvious to monitor Bunge’s
patient to ensure that the therapeutic agent was present at the desired
concentration, and to administer additional agent if the level was too low.
As Appellants’ other arguments do not persuade me that the Examiner erred
in concluding that the claims would have been obvious over the cited
references, I would affirm the Examiner’s rejections.

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