Ex Parte Zhang et al

Patent Trials and Appeals Board

Jul 9, 2019

14003663 - (D) (P.T.A.B. Jul. 9, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
14/003,663 11/18/2013
32692 7590 07/11/2019
3M INNOVATIVE PROPERTIES COMPANY
PO BOX 33427
ST. PAUL, MN 55133-3427
FIRST NAMED INVENTOR
Ying Zhang
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.
67337US004 1000
EXAMINER
PHAN, DOANTHI-THUC
ART UNIT PAPER NUMBER
1613
NOTIFICATION DATE DELIVERY MODE
07/11/2019 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):
LegalUSDocketing@mmm.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte YING ZHANG,
KRISTEN J. HANSEN, and AMY S. DETERMAN
Appeal 2018-001177
Application 14/003,663
Technology Center 1600
Before DONALD E. ADAMS, FRANCISCO C. PRATS, and
JEFFREY N. FREDMAN, Administrative Patent Judges.
FREDMAN, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal 1,2 under 35 U.S.C. § 134(a) involving claims to a
medical device comprising an array of microneedles. The Examiner rejected
the claims as obvious and on the ground of obviousness-type double
patenting. We have jurisdiction under 35 U.S.C. § 6(b). We affirm.
1 Appellants identify the Real Party in Interest as 3M Company and its
affiliate 3M Innovative Properties Company (see App. Br. 2).
2 We have considered the Specification of Sept. 6, 2013 ("Spec."); Final
Office Action of Sept. 22, 2016 ("Final Act."); Appeal Brief of June 12,
2017 ("App. Br."); Examiner's Answer of Sept. 18, 2017 ("Ans."); and
Reply Brief of Nov. 14, 2017 ("Reply Br.").
Appeal 2018-001177
Application 14/003,663
Statement of the Case
Background
"Delivery of a desired amount of an agent by mechanically
penetrating the stratum comeum can be compromised because of the
mechanical and surface properties of skin. For example, skin can deflect
and resist puncturing by very small piercing elements, causing non-uniform
penetration of the skin" (Spec. 1 :24--28). "Microneedle devices, comprising
solid microneedles coated with or containing certain local anesthetics in
solid form, have now been made, which provide a controlled, immediate,
and sustained dose of the local anesthetic to tissue underlying the stratum
comeum, such as the epidermis" (Spec. 2:12-15).
The Claims
Claims 1 and 5-20 are on appeal. Independent claim 1 is
representative and reads as follows:
1. A medical device, comprising:
an array of microneedles, and
a solid coating disposed on the microneedles,
wherein the solid coating comprises:
a local anesthetic selected from the group
consisting of lidocaine, prilocaine, and a combination
thereof; and
a local anesthetic dose-extending component
selected from the group consisting of alpha 1 adrenergic
agonists, alpha 2 adrenergic agonists, and a combination
thereof;
wherein the local anesthetic is present in an
amount of at least 1 wt-% based upon total weight of
solids in the coating, and
wherein the dose-extending component/local
anesthetic weight ratio is at least O.0001 : 1.
2
Appeal 2018-001177
Application 14/003,663
The Issues 3
A. The Examiner rejected claims 1 and 5-20 under 35 U.S.C. § I03(a) as
obvious over Gill, 4 Tokumoto, 5 Bharti, 6 and Chasin7 (Ans. 3-8).
B. The Examiner provisionally rejected claims 1 and 5-20 on the ground
of nonstatutory obviousness-type double patenting as being unpatentable
over claims 1 and 6-16 of copending Application No. 14/003,693 in view of
Tokumoto (Ans. 9-10).
A. 35 US.C. § 103(a) over Gill, Tokumoto, Bharti, and Chasin
The issues with respect to this rejection are:
(i) Does a preponderance of the evidence of record support the
Examiner's conclusion that Gill, Tokumoto, Bharti, and Chasin render the
method of the claims obvious?
(ii) If so, have Appellants presented evidence of secondary
considerations, that when weighed with the prior art evidence of
obviousness, is sufficient to support a conclusion of non-obviousness?
Findings of Fact
1. Gill teaches "[ c ]oated microneedle devices and methods of
coating microneedles have been developed to produce microneedles and
3 We note the rejection under 35 U.S.C. 112(b) was withdrawn (see Ans.
11 ).
4 Gill et al., US 2008/0213461 Al, published Sept. 4, 2008.
5 Tokumoto et al., WO 2008/139648 Al, published Nov. 20, 2008 (The
Examiner relies upon the English language equivalent US 2010/0280457
Al, published Nov. 4, 2010).
6 Bharti et al., Effect of Addition of Clonidine to Local Anaesthetic Mixture
for Peribulbar Block, 30 ANAESTH INTENSIVE CARE 438--41 (2002).
7 Chasin et al., US 2003/0185873 Al, published Oct. 2, 2003.
3
Appeal 2018-001177
Application 14/003,663
microneedle arrays having a variety of coatings improvements, enabling a
wide range of drug materials to be controllably coated onto microneedles
and then delivered into biological tissues, particularly for transdermal drug
delivery" (Gill ,r 34).
2. Gill teaches in "a preferred embodiment, the coating is adapted
to come off of the microneedle rapidly. Rapid dissolution is equal to or less
than 15 minutes, preferably less than 5 minutes ... This embodiment would
be particularly useful to deliver vaccines, local anesthetics ( e.g., lidocaine )"
(Gill ,r 58).
3. Gill teaches "[ e ]xamples of suitable hydrophobic drugs include
... clonidine" (Gill ,r 78).
4. Gill teaches in "another embodiment, the coating liquid is free
of excipients all together ... An example of a suitable drug for use in this
coating method is lidocaine, clonidine, and the like" (Gill ,r 80).
5. Tokumoto teaches "a microneedle coating method of coating
the microneedles formed on a microneedle device precisely, easily and in a
mass producible manner" (Tokumoto ,r 19).
6. Tokumoto teaches the "liquid coating solution or suspension
can contain an efficacious physiologically active substance in a
concentration of typically 0.1 to 65% by weight, preferably 1 to 30% by
weight, and more preferably 3 to 20% by weight" (Tokumoto ,r 74).
7. Tokumoto teaches the use of compositions including lidocaine
and clonidine (Tokumoto ,r 77).
8. Tokumoto teaches "[t]hese drugs are used singly or two or
more may be used in combination" (Tokumoto ,r 78).
4
Appeal 2018-001177
Application 14/003,663
9. Bharti teaches "Clonidine, a centrally active a2-agonist ... has
been extensively studied as an adjunct to general and regional anaesthesia"
(Bharti 438, col. 1 ).
10. Bharti teaches "[ a ]dmixture of clonidine to local anaesthetics
prolongs the duration of both anaesthesia and analgesia after various
neuraxial and peripheral nerve blocks" (Bharti 438, col. 1 ).
11. Bharti teaches "[ o ]ur results have shown that a combination of
clonidine 1 µg/kg with 2% lignocaine8-hyaluronidase mixture significantly
improved the duration of anaesthesia and analgesia after peribulbar block
compared to lignocaine alone" (Bharti 441, col. 1 ).
12. Chasin teaches "where the augmenting agent is included in the
formulation with the local anesthetic, the augmenting agent may be included
in controlled release form or in immediate release form" (Chasin ,r 33).
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."
KSR Int'! Co. v. Teleflex Inc., 550 U.S. 398,416 (2007).
"[W]here 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).
Analysis
We agree with the Examiner that Gill, Tokumoto, Bharti, and Chasin
render the claims obvious (Ans. 3-8; FF 1-12) and we adopt the Examiner's
position as our own. We consider Appellants' arguments below.
8 We note that lignocaine is an alternate name for lidocaine (see
https://www.dictionary.com/browse/lignocaine; accessed June 28, 2019).
5
Appeal 2018-001177
Application 14/003,663
Claim 1
Appellants contend
Gill does not give any reason to combine lidocaine with
clonidine in a solid microneedle coating, it also does not give
any reason to combine them in the amount or ratio recited in
claim 1 .... Tukomoto also fails to provide any reason why
clonidine and lidocaine would be formulated together in a
microneedle coating ... Bharti also teaches a system that is
specially adapted for use as a peribulbar block, and is
specifically not relevant or useful in topical delivery as are the
microneedles of the present claims ... Chasin does not teach
that clonidine and local anesthetic can be combined in a solid,
dissolvable coating.
(App. Br. 5).
We find Appellants' argument unpersuasive because it fails to
recognize that the rejection is based on the combination of references, not
any single reference alone. In re Keller, 642 F.2d 413,426 (CCPA 1981).
As the Examiner has pointed out, Gill and Tokumoto teach microneedle
medical devices with solid coatings composed of components including both
lidocaine and clonidine (FF 18). Tokumoto teaches drugs including
lidocaine and clonidine "may be used in combination" (FF 8) and Chasin
teaches that two component anesthetic compositions may be in different
forms (FF 12).
Bharti provides a strong reason to combine lidocaine and clonidine for
anaesthetic use because "[ o ]ur results have shown that a combination of
clonidine 1 µg/kg with 2% lignocaine-hyaluronidase mixture significantly
improved the duration of anaesthesia and analgesia after peribulbar block
compared to lignocaine alone" (FF 11 ).
Thus, the ordinary artisan interested in maximizing duration of
6
Appeal 2018-001177
Application 14/003,663
anesthesia using the microneedle devices of Gill and Tokumoto would have
reasonably combined clonidine and lidocaine because Bharti teaches the
combination improves duration (FF 10-11 ).
Appellants contend "the data of Chasin, shows that clonidine
sometimes increases and sometimes decreases the duration of local
anesthetic action. Thus, the skilled artisan would understand Chasin as
showing that the effect of clonidine on a local anesthetic's duration of action
is unpredictable" (App. Br. 6).
We find this argument unpersuasive. While Chasin does show that a
higher clonidine concentration decreases duration of anesthesia of buvacaine
(Chasin, Table 3), the obviousness rejection is drawn to a combination of
lidocaine and clonidine, not buvacaine. And Bharti expressly teaches that "a
combination of clonidine 1 µg/kg with 2% lignocaine-hyaluronidase
mixture significantly improved the duration of anaesthesia and analgesia"
(FF 11 ). Thus, as we balance the evidence, we find that Bharti, directed to a
combination within the scope of claim 1, is more persuasive of efficacy of
the combination of clonidine and lidocaine than Chasin, directed to a
combination that is not within the scope of claim 1.
Appellants contend that
the prior art (i) provides no reason for a person of ordinary skill
in the art would to combine clonidine with a local anesthetic in
a dissolvable solid coating on micro[ n ]eedles; and (ii) indicates
that the person of skill in the art would not reasonably expect to
succeed in obtaining any advantageous results by doing so.
(App. Br. 6).
We are not persuaded. As to the use of a dissolvable solid coating,
Gill teaches in "a preferred embodiment, the coating is adapted to come off
7
Appeal 2018-001177
Application 14/003,663
of the microneedle rapidly .... This embodiment would be particularly
useful to deliver vaccines, local anesthetics (e.g., lidocaine)" (FF 2). This is
a direct teaching to use anesthetics with microneedles and coatings that
rapidly dissolve. As to the expectation of success, both Gill and Tokumoto
support a general expectation of success in delivering anesthetics by
microneedles, and Bharti provides strong evidence that the combination of
clonidine and lidocaine would be expected to have superior analgesia
duration (FF 1-11 ). "Obviousness does not require absolute predictability of
success ... all that is required is a reasonable expectation of success." In re
Kubin, 561 F.3d 1351, 1360 (Fed. Cir. 2009).
Claim 1 - unexpected results
Appellants contend:
The examples in the present specification show that, when
formulated as solid, dissolvable coatings on microneedles in
accord with the current claims, combinations of a local
anesthetic dose-extending component and a local anesthetic
selected from the group consisting of lidocaine, prilocaine, and
a combination thereof can extend the duration of action the
local anesthetic ( as measured by extending the concentration of
local anesthetic in the tissue after administration). This result is
unexpected over the prior art, which shows at best that such a
combination has an unpredictable effect on the duration of the
local anesthetic.
(App. Br. 6-7).
We find this argument unpersuasive for a number of reasons. First, as
evidenced by Bharti, the combination of lidocaine and clonidine would be
expected to result in increased duration of analgesic and anesthetic effect
(FF 10-11 ), so this is the expected result, not an unexpected result. See In re
Skoner, 517 F.2d 947, 950 (CCPA 1975) ("Expected beneficial results are
8
Appeal 2018-001177
Application 14/003,663
evidence of obviousness of a claimed invention. Just as unexpected
beneficial results are evidence of unobviousness").
Second, Appellants do not point to any specific results in the
Specification, nor do Appellants identify any comparison of any specific
results with the closest prior art of Bharti ( or even Gill or Tokumoto ). See In
re Baxter Travenol Labs., 952 F.2d 388,392 (Fed. Cir. 1991) ("[W]hen
unexpected results are used as evidence of nonobviousness, the results must
be shown to be unexpected compared with the closest prior art.").
Third, not only do Appellants fail to demonstrate the unexpected
results, but Appellants fail to show that the breadth of alpha 1 adrenergic
agonist or alpha 2 adrenergic agonist or combinations thereof with lidocaine
or prilocaine produce the asserted unexpected results. Thus, the evidence is
not commensurate in scope with the recitations in claim 1. Unexpected
results must be "commensurate in scope with the degree of protection sought
by the claimed subject matter." In re Harris, 409 F.3d 1339, 1344 (Fed. Cir.
2005).
Claim 19
Appellants contend "the cited prior art does not provide any reason to
mix the required drugs in a solid dissolvible matrix in a dissolvable
microneedle (as differentiated from a dissolvable coating on a microneedle
that does not dissolve)." (App. Br. 7).
We find this argument unpersuasive because both Gill and Tokumoto
suggest dissolvable microneedles (see, e.g., Ans. 17-18). In particular, Gill
teaches "[b ]iodegradable microneedles can provide an increased level of
safety compared to non-biodegradable ones, such that they are essentially
harmless even if inadvertently broken off into the biological tissue" (Gill
9
Appeal 2018-001177
Application 14/003,663
,r 43). Similarly, Tokumoto teaches that for microneedles "particularly
preferable materials are biodegradable polymers" (Tokumoto ,r 52).
Claim 20
Appellants contend:
Claim 20 is similar to claims 1, and also recites "wherein upon
topically delivering the local anesthetic and the local anesthetic
dose-extending component to mammalian tissue, the
concentration of the local anesthetic in the mammalian tissue 30
minutes after delivery is not less than about 35% of the
concentration of the local anesthetic in the mammalian tissue
immediately after delivery." Not only do the arguments
presented above with respect to claim 1 apply to claim 20, but
claim 20 is also unobvious because the prior art does not
provide any suggestion of this feature.
(App. Br. 7).
We find this argument unpersuasive because Gill suggests "[ r ]apid
dissolution is equal to or less than 15 minutes, preferably less than 5
minutes" (FF 2). Thus, Gill suggests a desirability of delivery of all of the
composition within less than 15 minutes, exceeding the requirement of claim
20 for delivery within 30 minutes of at least 35% of the anesthetic. To the
extent that Gill differs from claim 20, Gill certainly demonstrates that
delivery time is an optimizable variable, and Appellants provide no evidence
that the delivery rate recited in claim 20 is anything other than optimized.
"[D]iscovery of an optimum value of a result effective variable in a known
process is ordinarily within the skill of the art." In re Boesch, 617 F.2d 272,
276 (CCPA 1980).
Claim 15
Appellants contend the "examples in the specification, while
representative of all of the dose extending components of claim 1, focus on
10
Appeal 2018-001177
Application 14/003,663
clonidine, apraclonidine, guanfacine. Thus, to the extent that the showing of
unexpected results in the specification is insufficient with regard to the
breadth of claim 1, it is certainly sufficient with regard to claim 15" (App.
Br. 8).
We find this argument unpersuasive for the same reason as discussed
above for claim 1, because the improved duration of anesthesia resulting
from the combination of lidocaine and clonidine is an expected result based
on the disclosure of Bharti (FF 10-11 ), not an unexpected result.
Conclusions of Law
(i) A preponderance of the evidence of record supports the
Examiner's conclusion that Gill, Tokumoto, Bharti, and Chasin render the
method of the claims obvious.
(ii) Appellants have not presented evidence of secondary
considerations, that when weighed with the evidence of obviousness, is
sufficient to support a conclusion of non-obviousness.
B. Provisional obviousness-type double patenting
Appellants contend that "there is no showing that the tetracaine,
ropivacaine, bupivacaine, and procaine recited in the claims of the
copending application are alpha 1 or alpha 2 adrenergic agonists" (App. Br.
9). Appellants contend that "[t]here is no rational basis for substituting
alpha I adrenergic agonists, alpha 2 adrenergic agonists, and a combination
thereof for the tetracaine, ropivacaine, bupivacaine, and procaine recited in
the copending claims" (App. Br. 9).
The Examiner responds that "Tokumoto mentions not only tetracaine
and procaine ( the local anesthetic dose-extending component of the
11
Appeal 2018-001177
Application 14/003,663
copending application), but clonidine (the local anesthetic dose-extending
component of claimed invention; clonidine is an alpha 2 adrenergic agonist"
(Ans. 20).
We agree with the Examiner. Claim 1 of the related US 14/003,693
application recites:
1. A medical device, comprising:
an array of microneedles, and
a coating disposed on the microneedles, wherein the
coating comprises:
a local anesthetic selected from the group consisting of
lidocaine, prilocaine, and a combination thereof; and
a local anesthetic dose-extending component selected
from the group consisting of tetracaine, ropivacaine,
bupivacaine, procaine and a combination thereof;
wherein the local anesthetic is present in an amount of at
least 1 wt-% based upon total weight of solids in the coating,
and
wherein the local anesthetic and the local
anesthetic_dose-extending component are in a non-eutectic
weight ratio;
wherein the coating further comprises at least one
excipient; and wherein upon topically delivering the local
anesthetic and the local anesthetic doseextending component to
mammalian tissue, a concentration of the local anesthetic in the
mammalian tissue 30 minutes after delivery is about 31 % to
about 54% than a concentration of the local anesthetic in the
mammalian tissue immediately after delivery.
(US 14/003,693, Arndt. Filed Nov. 27, 2018).
As already discussed above, Tokumoto teaches microneedles (FF 5)
that may be coated with lidocaine and clonidine (FF 7) in combination
(FF 8). Thus, we agree with the Examiner that the ordinary artisan would
have found it obvious to incorporate the known clonidine compound, known
12
Appeal 2018-001177
Application 14/003,663
for use in combination with lidocaine on microneedles, because Tokumoto
teaches such a combination (FF 5-8).
SUMMARY
We affirm the rejection of claims 1 and 5-20 under 35 U.S.C.
§ 103(a) as obvious over Gill, Tokumoto, Bharti, and Chasin.
We affirm the provisionally rejection of claims 1 and 5-20 on the
ground of nonstatutory obviousness-type double patenting as being
unpatentable over claims 1 and 6-16 of copending Application No.
14/003,693 in view of Tokumoto.
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
13