Ex Parte Rebec

Patent Trial and Appeal Board

Mar 30, 2016

11999530 (P.T.A.B. Mar. 30, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
111999,530 12/06/2007
71331 7590
NIXON PEABODY LLP
70 West Madison, Suite 3500
CHICAGO, IL 60602
04/01/2016
FIRST NAMED INVENTOR
Mihaila V. Rebec
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
ATTORNEY DOCKET NO. CONFIRMATION NO.
05DC042.l 8954
EXAMINER
DONOHUE, SEAN R
ART UNIT PAPER NUMBER
1618
NOTIFICATION DATE DELIVERY MODE
04/01/2016 ELECTRONIC
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.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
following e-mail address( es):
docketingchicago@nixonpeabody.com
ipairlink@nixonpeabody.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte MIHAILO V. REBEC
Appeal2013-010610
Application 11/999,530
Technology Center 1600
Before DONALD E. ADAMS, JEFFREY N. FREDMAN, and
ULRIKE W. JENKS, Administrative Patent Judges.
FREDMAN, Administrative Patent Judge.
DECISION ON APPEAL
r-T"I .. • • .. 1 .. ,..... ,_ TT r'1 I'\ l\ -1,..... Al • "1 • "1 • , ,.. .. ims 1s an appear unaer j) u.~.L. s U4 mvo1vmg crnm1s to a memoa
of using a diffusion-based, continuous monitoring system to monitor the
effectiveness of delivering a therapeutic drug. The Examiner rejected the
claims as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We affirm.
1 Appellant identifies the Real Party in Interest as Bayer
HealthCare LLC (see App. Br. 2).
Appeal2013-010610
Application 11/999,530
Statement of the Case
Background
"[T]he effect of delivering the therapeutic drugs may vary in aspects
such as how long does the drug acts [sic] for on an individual and how does
the drug react with that individual. Because of this variation, some
individuals are individually monitored. This monitoring process is referred
to as therapeutic drug monitoring" (Spec. i-f 3).
The Claims
Claims 1-23 are on appeal. Independent claim 1 is representative and
reads as follows:
1. A method of using a diffusion-based, continuous-monitoring system
to monitor the effectiveness of delivering a therapeutic drug, the method
comprising the acts of:
creating at least one diffusion channel in an area of skin;
maintaining the at least one diffusion channel for a desired duration;
continuously monitoring the levels of the therapeutic drug, the levels
of a metabolite of the therapeutic drug or the levels of a substance that is
affected by the therapeutic drug in the area of the skin for the desired
duration via a diffusion-based, continuous-monitoring device; and
analyzing the levels of the therapeutic drug, the metabolite of the
therapeutic drug or the substance that is affected by the therapeutic drug so
as to determine the effectiveness of delivering the therapeutic drug.
2
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Application 11/999,530
The Issue2
The Examiner rejected claims 1-23 under 35 U.S.C. § 103(a) over
Yuzhakov,3 Petersen,4 Patel,5 Eppstein,6 and Kellogg7 (Ans. 3-13).
Findings of fact
1. The Specification teaches that:
Examples of diffusion-enhancing materials that may
be used in the diffusion-based, continuous-monitoring
system include, but are not limited to, hydrogels, liquids and
a liquid-stabilizing layer containing a liquid or hydrogel.
The diffusion-enhancing material also desirably assists in
hydrating the skin and maintaining an opening in the skin.
By maintaining the opening, a liquid bridge is formed such
that the therapeutic drug/metabolite/affected substance
diffuses from a layer in the skin through the opening. The
liquid bridge may be between a hydrogel/liquid and a body
fluid such as ISP (interstitial fluid) or a whole blood sample.
(Spec. iTiT 38-39).
2. The Specification teaches that "[t]o increase the porosity of skin
(e.g., the stratum comium, epidermis and/or dermis), chemical agents and
physical agents may be used .... Some non-limiting examples of chemical
agents that may be used include d-limonene, L-limonene, and alpha-
terpinene" (Spec. iTiT 24--25).
2 We note that the double patenting rejection is moot in view of the
abandonment of U.S. Patent Application No. 12/531,634 on Oct. 4,
2013.
3 Yuzhakov et al., US 6,931,277 Bl, issued Aug. 16, 2005.
4 Petersen et al., US 5,534,260, issued July 9, 1996.
5 Patel et al., US 4,863,970, issued Sept. 5, 1989.
6 Eppstein, US 5,722,397, issued Mar. 3, 1998.
7 Kellogg et al., US 2006/0015058 Al, published Jan. 19, 2006.
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Application 11/999,530
3. The Specification teaches that the "chemical and physical
agents discussed above in the generally short term may also be used in
medium continuous-testing periods to increase and maintain the porosity of
the skin" (Spec. i-f 32).
4. Yuzhakov teaches that:
The present invention relates generally to medical
devices and is particularly directed to a fluid dispensing
device and a fluid sampling device of the type which, in one
embodiment penetrates the stratum comeum and epidermis,
but not into the dermis of skin, and in another embodiment
penetrates into the dermis so as to interface with blood or
other biological fluids. The invention is specifically
disclosed as an array of microneedles which painlessly and
with minimal trauma to the skin enable fluid transfer either
into a body as a dispensing device, or from the body to
sample body fluid.
(Yuzhakov, col. 1, 11. 13-22).
5. Yuzhakov teaches "to provide a microneedle array as part of a
closed-loop system to control drug delivery, based on feedback information
that analyzes body fluids, which can achieve real time continuous dosing
and monitoring of body activity" where the microneedle array can "either
deliver drugs or to facilitate biological fluid sampling (e.g., sampling
interstitial fluids and/or blood) through the hollow microneedles or pores
made through skin via solid microneedles" (Yuzhakov, col. 3, 11. 16-20; col.
4, 11. 4--11; emphasis added).
6. Yuzhakov teaches that a "[c]ontroller 720 preferably comprises
a type of microchip that contains a central processing unit" with a "liquid
crystal display" (Yuzhakov, col. 25, 11. 36-50).
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Application 11/999,530
7. Yuzhakov teaches that "[t]he use of chemical enhancers,
ultrasound, or electric fields may also be used to increase transdermal flow
rate when used with the microneedle arrays of the present invention"
(Yuzhakov, col. 5, 11. 16-20).
8. Yuzhakov teaches that:
The present invention can thereby be used with medical
devices to dispense drugs by electrophoretic/microneedle
enhancement, to sample body fluids ... and a drug delivery
system with fluid sampling feedback using a combination of the
other two devices. For example, the body-fluid sensor can be
used for a continuous or periodic sampling noninvasive
measurement of blood glucose level by extracting glucose
through the skin by reverse iontophoresis, and measuring its
concentration using a bioelectrochemical sensor. The drug
delivery portion of this invention uses the microneedle array to
provide electrodes that apply an electric potential between the
electrodes.
(Yuzhakov, col. 5, 11. 34---49).
9. Figure 28 ofYuzhakov is reproduced below:
5
,,.,.-- 600 ,
Appeal2013-010610
Application 11/999,530
"FIG. 28 depicts an electrophoretically enhanced fluidic drug delivery
apparatus that is based upon a hollow microneedle array, generally
designated by the reference numeral 600. Drug-delivery apparatus 600
includes a plurality of microneedles 630, which are each hollow"
(Yuzhakov, col. 23, 11. 43--46).
10. Yuzhakov teaches that:
The drug delivery apparatus 600 can be used for a
continuous non-invasive medical device that can
continuously deliver a fluidic drug through the skin and into
the body. For example, insulin could be delivered to the
blood stream via the microneedles 531, through the stratum
comeum 540 and epidermis 542, and also into the dermis
544
(Yuzhakov, col. 24, 11. 27-32; emphasis added).
11. Figure 49 of Yuzhakov is reproduced below:
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X; ~\ ,,.
........................
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;_r, '''-... .... ~ L:?X
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4 9 ~ ... ~iC:B~)Nf.(Q:.:: :S.EPAR'/', 110~·.: . !'..(.~-t;
"FIG. 49 is a graph showing the effect of microneedle separation versus
transdermal flux" (Yuzhakov, col. 10, 11. 31-32). Figure 49 teaches that the
"the transdermal flux rate of normal skin without any microneedles, in the
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Application 11/999,530
above units of five (5) micrograms per square centimeter per 24 hours time"
(Yuzhakov, col. 32, 11. 12-15).
12. Kellogg teaches methods "for transporting a substance across a
biological membrane comprising the steps of applying a delipidation agent
to a portion of the biological membrane, applying a hydration agent to the
portion of the biological membrane, sonicating the portion of the biological
membrane, and transporting the substance across the biological membrane"
(Kellogg, Abstract).
13. Figure 20 of Kellogg is reproduced below:
"FIG. 20 is a graph of sensor response versus blood glucose levels"
(Kellogg ii 64).
14. Kellogg teaches that "meter 212 may provide an interface that
allows information be downloaded to an external device, such as a computer.
Such an interface may allow the connection of interface cables, or it may be
a wireless interface" (Kellogg ii 102). Kellogg teaches that
Meter 404 may incorporate power and electronics to control
the periodic extraction of body fluid, to detect analyte, and
to present the analyte concentration in a continuous manner.
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Application 11/999,530
Meter 404 may contain electronics and software for the
acquisition of sensor signals, and may perform signal
processing, and may store analysis and trending information.
(Kellogg ,-r 112).
15. Petersen teaches "penetration enhancers ... are compositions
which enhance the permeation of biologically active agents (e.g. drugs)
through the skin of an animal. Such compositions include ... limonene,
terpenes" (Petersen, col. 3, 11. 14--19).
16. Patel teaches "improved compositions and methods for
improving the penetration of a broad category of pharmaceutically-active
agents which are lipophilic or hydrophilic including salts and which produce
little or no skin irritation to human or animal tissue systems" (Patel, col. 3,
11. 36-42).
17. Patel teaches that "[p ]enetration enhancers have been primarily
categorized according to their ability to enhance permeant flux via three
pathways .... The second pathway is a continuous non-polar pathway
consisting of lipids .... Solvents such as DMSO, 2-pyrrolidone, and
dimethylformamide, previously mentioned also appear able to solubilize or
fluidize lipids" (Patel, col. 1, 11. 42-60).
18. Patel teaches that "[ e ]xamples of cardiac drugs are ... digoxin"
(Patel, col. 9, 11. 1-5).
19. Eppstein teaches that "[a] method of enhancing the permeability
of the skin or mucosa to an analyte for diagnostic purposed is described
utilizing ultrasound or ultrasound plus a chemical enhancer" (Eppstein,
Abstract).
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Application 11/999,530
Principles of Law
"The combination of familiar elements according to known methods
is likely to be obvious when it does no more than yield predictable results."
KSRint'l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007). "If a person of
ordinary skill can implement a predictable variation, § 103 likely bars its
patentability." Id. at 417.
Analysis
We adopt the Examiner's findings of fact and reasoning regarding the
scope and content of the prior art (Ans. 3-13; FF 1-19) and agree that the
claims are rendered obvious by Yuzhakov, Petersen, Patel, Eppstein, and
Kellogg. We address Appellant's arguments below.
We begin with claim interpretation because before a claim is properly
interpreted, its scope cannot be compared to the prior art. During
prosecution, the USPTO interprets terms in a claim using the broadest
reasonable interpretation in light of the Specification. See In re Morris, 127
F.3d 1048, 1054 (Fed. Cir. 1997).
The phrase at issue in claim 1 is "maintaining the at least one
diffusion channel for a desired duration" with claim 14 further limiting the
"maintaining" step by "introduction to the area of skin of a chemical agent, a
physical agent, or both" and claim 18 still further limiting the "maintaining"
step to a "duration of at least one hour."
The Specification teaches that the "maintaining" may occur by contact
of liquid chemical agents with the skin (FF 1-3 ), but provides no specific
duration range that limits the "desired duration" required by claim 1. The
Specification further identifies specific chemical agents including limonene
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Application 11/999,530
and terpinene (FF 2) that "may also be used in medium continuous-testing
periods to increase and maintain the porosity of the skin" (FF 3).
We therefore interpret the "maintaining" requirement as
encompassing administration of agents including limonene to the skin during
the continuous-monitoring diffusion process of the claims to necessarily
result in "maintaining" the diffusion channel for "a desired duration."
Claim 1
Appellant contends that "Yuzhakov does not teach or suggest actively
'maintaining' the microneedle-generated penetrations for this test period (or
any other period for that matter)" (Br. 11 ). Appellant contends that
"Yuzhakov's microneedle-generated channels are allowed to naturally close,
without any active maintenance of the channels for the duration of the
testing" (Br. 11 ).
We do not find this argument persuasive because the rejection relies
upon the combination of Yuzhakov with additional references including
Peterson and Patel. Yuzhakov discloses at multiple places maintaining
"continuous" dosing through the at least one diffusion channel for a desired
duration (FF 4--11). In particular, Yuzhakov specifically teaches that
"chemical enhancers ... may also be used to increase transdermal flow rate
when used with the microneedle arrays" (FF 7), and Peterson and Patel
suggest the use of penetration enhancers (FF 15-1 7) including the specific
penetration enhancers limonene and terpinene (FF 15).
Thus, the ordinary artisan would have reasonably employed
penetration enhancers such as limonene and terpinene in the method of
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Application 11/999,530
Yuzhakov to increase flow rate of the microneedle arrays (FF 6, 15),
consistent with the Examiner's reliance on Petersen (see Ans. 10).
We note that limonene is the same agent used by Appellant's own
Specification for "maintaining" a diffusion channel (FF 2-3) and therefore
the combination of Yuzhakov method with penetration enhancers and
Peterson's specific limonene penetration enhancer would inherently achieve
the same result of "maintaining" a diffusion channel for a "desired"
duration, at least as long as therapeutic drug is being administered, and body
fluids monitored, by Yuzhakov (FF 5, 15).
We recognize, but find unpersuasive, Appellant's arguments relating
to inherency (Br. 13). Inherency may be relied upon in obviousness
determinations, and where the Examiner provides reasonable evidence
supporting a finding of inherency, as with the identity of penetration
enhancers in the prior art with the chemical agents used for "maintaining"
diffusion channels here, the burden reasonably shifts to Appellant to rebut
the Examiner's position with evidence. Appellant has not provided rebuttal
evidence. See In re Best, 562 F.2d 1252, 1255 (CCPA 1977) ("Where, as
here, the claimed and prior art products are identical or substantially
identical ... the PTO can require an applicant to prove that the prior art
products do not necessarily or inherently possess the characteristics of his
claimed product. ... Whether the rejection is based on 'inherency' under
35 U.S.C. § 102, on 'prima facie obviousness' under 35 U.S.C. § 103,
jointly or alternatively, the burden of proof is the same, and its fairness is
evidenced by the PTO' s inability to manufacture products or to obtain and
compare prior art products.").
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Application 11/999,530
We also note that Appellant's contention that Yuzhakov's channels
"are allowed to naturally close" is not based on any specific evidence that
the channels do not remain open for a "desired" duration but rather on
Figure 49, which simply shows the effect of microneedle separation versus
transdermal flux (FF 11 ). Figure 49 does not, by itself, provide sufficient
evidence to demonstrate a teaching away from the use of penetration
enhancers including the obvious use of Peterson's limonene, nor does Figure
49 even teach that the channels do not remain open for a "desired" duration.
See In re Fulton, 391 F.3d 1195, 1201 (Fed. Cir. 2004).
Appellant contends that the "nature of Yuzhakov's proposed
continuous measurement of blood-glucose levels is not clearly defined in the
reference" (Br. 12).
We are not persuaded. Yuzhakov teaches continuous monitoring (FF
8, 10), and Figure 49 suggests 24 hour time measurements (FF 11 ).
Moreover, we agree with the Examiner that Kellogg also discloses
continuous monitoring periods, specifically teaching "maintaining diffusion
channels and continuous monitoring of blood glucose for at least 350 min"
(Ans. 17, FF 13). Given this disclosure of continuous therapeutic
monitoring in both Yuzhakov and Kellogg, we agree with the Examiner that
the skilled artisan would have viewed the specific duration of the continuous
monitoring period as routinely optimizable. "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 (CCPA 1955).
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Application 11/999,530
Claims 14 and 18
Appellant contends that "Yuzhakov also fails to depict, describe, or
suggest maintaining the diffusion channel( s) 'throughout a desired duration
via introduction to the area of skin of a chemical agent, a physical agent, or
both, during the desired duration'" (Br. 12).
We are not persuaded for the reasons given above. Yuzhakov
specifically teaches administration of penetration enhancers (FF 8) and
Peterson suggests penetration enhancers such as limonene (FF 15) where the
Specification recognizes limonene as a chemical agent that maintains a
diffusion channel for a desired duration (FF 2-3). See In re Merck & Co.,
800 F.2d 1091, 1097 (Fed. Cir. 1986) ("Non-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.").
We further note that, as already discussed, the time period for
maintaining is reasonably identified as a routinely optimizable variable,
encompassing at least 350 minutes (FF 13), that overlaps the hour required
by claim 18.
Appellant separately argues that "the Examiner is unable to point to a
specific teaching within columns 25 and 26 of Yuzhakov's specification that
discloses a similarly configured communications interface that is adapted to
connect with a receiving module via a communications link" (Br. 13).
We are not persuaded. Claim 18 simply requires a "communications
interface that is adapted to connect with a receiving module via a
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Application 11/999,530
communications link." As the Examiner points out, Yuzhakov teaches a
microchip controller while Kellogg teaches that a device controller may
interface by a communications link either by cable or wireless with an
external device (FF 6, 14; cf Ans. 21 ). Appellant does not identify any
specific element that is not suggested by the combination of Yuzhakov with
Kellogg, instead arguing Yuzhakov alone without the teachings of the
Kellogg reference. In re Keller, 642 F.2d413, 425(CCPA1981).
Claim 4
Appellant contends that Yuzhakov "does not teach maintaining at
least one diffusion channel and continuously monitoring the levels of the
therapeutic drug, the levels of a metabolite of the therapeutic drug, or the
levels of a substance that is affected by the therapeutic drug for 8 or 24
hours" (Br. 14).
We are not persuaded because, even ifYuzhakov's disclosure of 24
hours is insufficient (FF 11 ), Kellogg teaches 350 minutes, or almost 6
hours, which reasonably suggests that the time period is routinely
optimizable variable as discussed above. Appellant provides no evidence
that optimizing the time to 8 hours provides any secondary consideration or
unexpected result (cf Ans. 20).
Claim 5
Appellant contends that "Yuzhakov never suggests using the hydrogel
and/or insulin to maintain the microneedle-generated channels" (Br. 15).
We are not persuaded for the reasons already given. To briefly recap,
the Examiner relies upon Yuzhakov for the suggestion of chemical
permeation enhancers (cf Ans. 9; FF 9), while relying upon Petersen to
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Application 11/999,530
suggest specific chemical enhances including limonene and terpene (cf Ans.
10; FF 15). The combination of Yuzhakov and Petersen therefore suggests
the use of chemical agents including limonene to enhance drug and
bioanalyte permeation, and inherently satisfying the requirement of claim 5
"wherein [] maintaining the at least one diffusion channel includes
introducing to the area of skin a chemical agent." Appellant provides no
evidence rebutting this position.
Claim 8
Appellant contends that "[a]t no point in this section [ofYuzhakov],
or anywhere else in the reference as for [sic] as Appellant's [sic] can tell,
does Yuzhakov teach or suggest 'continuously monitoring the levels of
[insulin] ... for the desired duration via a diffusion-based, continuous-
monitoring device"' (Br. 15).
We are not persuaded. Claim 8 simply requires that "levels of the
therapeutic drug are continuously monitored." Yuzhakov is replete with
teachings "for a continuous or periodic sampling noninvasive measurement
of blood glucose level" (FF 8; emphasis added), where the blood glucose
level represents an indirect measurement of insulin levels in the patient and
insulin dosing information (FF 10).
Claims 19 and 20
Appellant contends that "Yuzhakov does not teach either of the"
limitations of claims 19 and 20 (Br. 15) regarding transmitting drug or
metabolite levels via a communications link or receiving drug delivery
instructions via the communcations link.
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Application 11/999,530
We do not find this argument persuasive because the rejection does
not rely solely upon Yuzhakov, but includes Kellogg, who teaches that a
meter may analyze and store analyte levels as well as communicate by a
wireless interface with a computer (FF 14). This teaching, combined with
Yuzhakov's teaching of a microchip controller (FF 6) reasonably renders
obvious the requirement of claim 19 for transmitting analyte levels to a
computer as well as uploading instructions to the microchip of Yuzhakov
over Kellogg's wireless link from a computer (FF 14). The Examiner
reasons that this combination would have been obvious because "wireless
transfer of data would provide the advantage of interfacing with external
device thereby minimizing the need for integrated storage and processing of
data" on the microchip of Yuzhakov (Ans. 13).
SUMMARY
We affirm the rejection of claims 1, 4, 5, 8, 14, and 18-20 under
35 U.S.C. § 103(a) as obvious over Yuzhakov, Petersen, Patel, Eppstein, and
Kellogg. Claims 2, 3, 6, 7, 9-13, 15-17, and 21-23 fall with claims 1, 14,
and 18. 37 C.F.R. § 41.37(c)(l)(iv).
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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