Ex Parte Wen et al

Patent Trial and Appeal Board

Feb 14, 2018

14172591 (P.T.A.B. Feb. 14, 2018)

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.
14/172,591 02/04/2014 Tian Wen 106150-1283 5148
30542 7590 02/16/2018
FOT FY Rr T ARDNFR T T P
EXAMINER
3000 K STREET N.W. FUBARA, BLESSING M
SUITE 600
WASHINGTON, DC 20007-5109 ART UNIT PAPER NUMBER
1613
NOTIFICATION DATE DELIVERY MODE
02/16/2018 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):
ipdocketing @ foley. com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte TIAN WEN, LIU LIU, MINGQI LU, JIESHAN BAI,
and Y. JOSEPH MO
Appeal 2016-003615
Application 14/172,5911
Technology Center 1600
Before DEBORAH KATZ, ULRIKE W. JENKS, and DAVID COTTA,
Administrative Patent Judges.
COTTA, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims directed to
method for treating tissue ischemia. The Examiner rejected the claims on
appeal under 35 U.S.C. § 103(a) as obvious and on the grounds of
obviousness-type nonstatutory double patenting.
We reverse the obviousness rejection, affirm the double patenting
rejections, and enter a new ground of rejection.
1 According to Appellants, the real party in interest is Nexmed Holdings,
Inc. App. Br. 2.
Appeal 2016-003615
Application 14/172,591
STATEMENT OF THE CASE
The Specification discloses that “[vjasospasm is a constriction of
blood vessels, resulting in ischemia of the tissue supplied by the blood
vessels.” Spec. 2. “Topical agents, such as magnesium sulfate, lidocaine,
papaverine and chlorpromazine have been reported to successfully relieve
vasospasm.” Id.
The Specification further discloses that prostaglandin Ei, a
commercially available derivative of prostanoic acid, “is a vasodilator useful
to maintain open blood vessels and, therefore, to treat peripheral vascular
disease among other ailments.” Id. at 3. According to the Specification,
“the potential benefits from transdermal delivery of prostaglandin Ei have
long been recognized.” Id. However, “prior efforts at developing a topical
composition for prostaglandin delivery have not been fully successful”
because prior formulations did not “sufficiently permeate the skin to provide
drug concentration levels comparable to those obtained from other drug
delivery routes.” Id. “To overcome this problem, topical drug formulations
typically include a skin penetration enhancer.” Id. The Specification
discloses that a “wide variety of compounds have been evaluated as to their
effectiveness in enhancing the rate of penetration of drugs through the skin.”
Id. at 4.
The Specification states that the inventors “found that administration
of prostaglandin compositions comprising a penetration enhancer relieves
constriction of a blood vessel in vasospasm and restores blood flow.” Id.
The Specification discloses: “The method and compositions are useful for
the relief of vasospasm in several conditions, including vasospasm occurring
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Application 14/172,591
during and following replantation surgery.” Id. “In other embodiments, the
present invention provides methods of treating tissue ischemia.” Id.
Claims 65—76 are on appeal. Claim 65 is illustrative and reads as
follows:
65. A method of treating tissue ischemia comprising:
applying directly to a surface of a tissue of a
subject needing treatment of tissue ischemia a
composition comprising:
one or more of prostaglandin El, a
pharmaceutically acceptable salt of prostaglandin El, and
a Ci to C4 alkyl ester of prostaglandin El or a
pharmaceutically acceptable salt thereof, wherein the
dose per application is about 0.08 mg to about 0.64 mg of
prostaglandin El;
a penetration enhancer selected from the group
consisting of an alkyl-(N-substituted amino) alkanoate,
an alkyl-2-(N,N-disubstituted amino) alkanoate, an (N-
substituted amino) alkanol alkanoate, an (N,N-
disubstituted amino) alkanol alkanoate, a
pharmaceutically acceptable salt thereof, and a mixture
thereof;
a shear-thinning polymer thickener selected from
the group consisting of a shearthinning polysaccharide
gum and a shear-thinning polyacrylic acid polymer;
a lipophilic component that is selected from the
group consisting of an aliphatic Ci to Cg alcohol, an
aliphatic Cg to C30 ester, a liquid polyol and a mixture
thereof; water and
a buffer system that provides a buffered pH.
App Br. 12.
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Application 14/172,591
The claims stand rejected as follows:
Claims 65—76 were rejected under 35 U.S.C. § 103(a) as obvious over
Buyuktimkin2 as evidenced by Clifford.3 Final Act.4 3.
Claim 65—76 were rejected on the ground of nonstatutory double
patenting over claims 1—27 ofU.S. Patent No. 6,046,244 (Buyuktimkin).
Final Act. 11.
Claim 65—76 were rejected on the ground of nonstatutory double
patenting over claims 1—29 ofU.S. Patent No. 6,414,028 Bl. Id.
Claim 65—76 were rejected on the ground of nonstatutory double
patenting over claims 1—37 ofU.S. Patent No. 7,105,572 B2. Id.
Claim 65—76 were rejected on the ground of nonstatutory double
patenting over claims 1—18 ofU.S. Patent No. 6,486,207 B2. Id.
Claim 65—76 were rejected on the ground of nonstatutory double
patenting over claims 1—31 ofU.S. Patent No. 6,825,234 B2. Id.
Claim 65—76 were rejected on the ground of nonstatutory double
patenting over claims 1—32 ofU.S. Patent No. 6,323,241 Bl. Id.
FINDINGS OF FACT
1. Buyuktimkin discloses “[a] topical composition ... for
transdermal application of prostaglandin Ei . . . compris[ing] prostaglandin
Ei, a penetration enhancer, a polysaccharide gum, a lipophilic compound,
and an acidic buffer system.” Buyuktimkin Abstract.
2 Buyuktimkin et al., U.S. Patent No. 6,046,244, issued Apr. 4, 2000
(“Buyuktimkin”).
3 Clifford et al., Treatment of Vasospastic Disease with Prostaglandin Ej,
281 British Medical Journal 1031-1034 (1980) (“Clifford”).
4 Office Action mailed Jan. 14, 2015 (“Final Act.”).
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Application 14/172,591
2. Buyuktimkin discloses: “Prostaglandin Ei is a vasodilator
useful to maintain open blood vessels and therefore, to treat peripheral
vascular disease among other ailments.” Id. at col. 1,11. 27—29.
3. Buyuktimkin discloses: “These compositions can be used for
prolonged treatment of peripheral vascular disease, male impotency and
other disorders treated by prostaglandin Ei.” Id. at col. 8,11. 6—8.
4. Table 1 of Buyuktimkin is reproduced below.
TABLE 1
Ibpical Pro^Agkuuuri E* OomoestLoiVi
F F 0Ingre-disnt (wt %) A B c D
Pint A: p.'djydiLkd ioeusi beau gum 3 3 3 3 3 3 3
water/buftV {pH 55) 8:1 81 81 83 S3 SI S':
:= ticrose a tea rate 0,5 0.5 0.5 0.5 0.5 0.5
Part B: p:’osiagJ:tndj>< liL 0J 0.2 0.3 0.4 0,4 0.5 0.4
ODAIF 5 5 5 5 5 5 5
ethaitoJ 5 5 5 5 5 5 10
ethyl iauiatc 5 .5 5 5 5 5 —
Id. at col. 10,11. 38—50. Table 1 “contains a list of ingredients” for
compositions A—G of Buyuktimkin. Id. at col. 8,1. 54.
5. Buyuktimkin discloses: “Prostaglandin Ei is well known to
those skilled in the art. Reference may be had to various literature
references for its pharmacological activities, side effects, and normal dosage
ranges.” Id. at col. 2,11. 52—55.
6. Buyuktimkin discloses: “The quantity of prostaglandin Ei in the
pharmaceutical compositions of the present invention is a therapeutically
effective amount and necessarily varies according to the desired dose, the
dosage form (e.g., suppository or topical), and the particular form of
prostaglandin Ei used.” Id. at col. 2,11. 63—67.
7. Buyuktimkin discloses: “The resulting topical composition,
when compared to exhibits the advantageous properties described above,
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Application 14/172,591
including improved prostaglandin Ei permeation and bioavailability without
drug overloading, reduced skin damage and related inflammation, and
increased flexibility in design of dosage forms.” Id. at col. 8,11. 1—6.
8. Buyuktimkin discloses “[application of prostaglandin Ei in a
topical composition of the present invention to the skin of a patient allows a
predetermined amount of prostaglandin Ei to be administered continuously
to the patient.” Id. at col. 8,11. 11—14.
9. The Specification discloses “[vjasospasm is a constriction of
blood vessels, resulting in ischemia of the tissue supplied by the blood
vessels.” Spec. 2.
ANALYSIS
Obviousness
Claim 65, the only independent claim on appeal, requires that the
“dose per application is about 0.08 mg to about 0.64 mg of prostaglandin
El.” In finding the pending claims to be obvious, the Examiner found that
“Buyuktimkin teaches 0.001 gram in Table 1 and from 0.1 to 0.5% which is
about 1 mg to 5 mg . . . indicating that the amount of the prostaglandin can
be varied.” Ans. 6. The Examiner then concluded that this was close
enough to the 0.64 mg recited in the claims to support a prima facie case of
obviousness. Id. at 6—7; see also id. at 9-10.
Appellants argue that Buyuktimkin discloses only the “relative
amount in wt%” and that the Examiner’s assertion that Buyuktimkin
discloses an “actual amount (in micro gram, mg, or g) of PGE1” is “pure
speculation.” App. Br. 8.
We find that Appellants have the better position. The Examiner relies
on Table 1 of Buyuktimkin as disclosing a “0.08 mg to about 0.64 mg” dose
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Application 14/172,591
of prostaglandin Ei. Final Act. 6—7; Ans. 9-10. However, Table 1 discloses
the weight of prostaglandin Ei only as a percentage of the total weight of the
composition. FF4. Buyuktimkin does not disclose total amount of the
topical composition applied. Therefore, the disclosure is insufficient to
establish the amount of active ingredient applied to the tissue. Because the
Examiner has not articulated any other basis on which to find that the cited
prior art discloses or suggests the claimed dosage, we reverse the
Examiner’s rejection of claims 65—76 as obvious over Buyuktimkin as
evidenced by Clifford.
New Ground of Rejection
As discussed above, we disagree with the Examiner that
Buyuktimkin’s Table 1 expressly discloses the claimed dosage. However,
we find that the claimed dosage would have been the obvious result of
routine optimization. We agree with the Examiner that the other elements of
the recited claims are disclosed or suggested by Buyuktimkin. Accordingly,
for the reasons discussed below, under the provisions of 37 C.F.R.
§ 41.50(b), we enter the following new ground of rejection: Claims 65—76
are rejected as obvious over Buyuktimkin.
Buyuktimkin discloses a composition comprising prostaglandin Ei, a
penetration enhancer, a polysaccharide gum, a lipophilic compound, and an
acidic buffer system. FF1. While Buyuktimkin does not expressly disclose
the claimed dosage as applied to the tissue, Buyuktimkin does disclose that
prostaglandin Ei was “well known to those skilled in the art” and suggests
consulting the literature on “normal dosage ranges.” FF5. Buyuktimkin also
discloses that its composition “allows a predetermined amount of
prostaglandin Ei to be administered” and provides “flexibility in design of
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Application 14/172,591
dosage forms.” FF7, FF8. Buyuktimkin further discloses varying the
quantity of prostaglandin Ei present in a composition “according to the
desired dose, the dosage form (e.g., suppository or topical), and the
particular form of prostaglandin Ei used.” FF6. The skilled artisan would
thus have recognized the quantity of prostaglandin Ei was a result effective
variable. See Merck & Co. v. Bio craft Labs., Inc., 874 F.2d 804, 809 (Fed.
Cir. 1989) (drug dosage limitations resulted from routine experimentation);
Eli Lilly & Co. v. Teva Pharms USA, Inc., 619 F.3d 1329, 1342 (Fed. Cir.
2010) (“[Conducting clinical trials to test for an optimal dose for a drug ‘is
generally a routine process[’].” (citation omitted)). Accordingly, we find
that the skilled artisan would have arrived at the claimed amount of
prostaglandin Ei through the process of routine optimization. In re Boesch,
617 F.2d 272, 276 (CCPA 1980) (“discovery of an optimum value of a result
effective variable in a known process is ordinarily within the skill of the
art”).
In finding the pending claims obvious, the Examiner found that
Buyuktimkin disclosed or suggested all of the remaining elements of claims
65—76. With respect to the limitation requiring application of the
composition “to a surface of a tissue of a subject needing treatment of tissue
ischemia,” the Examiner found that “[o]ne of the goals of Buyuktimkin is to
keep blood vessels open which inherently meets the goal of the claims so
that although, Buyuktimkin does not use the term of ‘tissue ischemia’ . . .
[applying the composition] would inherently . . . produce the effect of
improving tissue ischemia in skin tissue.” Final Act. 5. Alternatively, the
Examiner found that “prostaglandin Ei is a vasodilator and potent inhibitor
of platelet aggregation and is used to treat vasospastic disease as evidenced
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Application 14/172,591
in the background of Buyuktimkin and also by Clifford.” Id. at 5—6. The
Examiner thus concluded that the skilled artisan would reasonably expect
that applying Buyuktimkin’s composition would “keep blood vessels open
as a vasodilator according to the background disclosure of Buyuktimkin and
. . . provide prolonged treatment of peripheral vascular disease and other
diseases treated with prostaglandin El.” Id. at 6.
Except as discussed above, we adopt the Examiner’s findings of fact
and reasoning regarding the scope and content of the Buyuktimkin as
applied to claims 65—76. We find that Buyuktimkin discloses the remaining
limitations of claims 65—76 (i.e., the limitations other than the amount of
prostaglandin Ei present) for the reasons provided by the Examiner.
Accordingly, under the provisions of 37 C.F.R. § 41.50(b), we reject claims
65—76 as obvious over Buyuktimkin. We address Appellants’ arguments
below.
Appellants argue that the Examiner “relies on the fact that, ‘ [i]t is
known in the art that prostaglandin El is a vasodilator and potent inhibitor of
platelet aggregation and is used to treat vasospastic disease” and that this
statement is “unsubstantiated by evidence.” App. Br. 9 (emphasis omitted).
We disagree. Buyuktimkin expressly discloses that “[pjrostaglandin Ei is a
vasodilator useful to maintain open blood vessels and therefore, to treat
peripheral vascular disease among other ailments” and that its compositions
can be used for “treatment of peripheral vascular disease, male impotency
and other disorders treated by prostaglandin Ei.” FF2, FF3.
Appellants argue that “the state of the art provides no reasonable
expectation of success that PGE1 would be effective in treating vasospastic
disease, and teaches away or at the minimum provides no reasonable
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motivation to use PGE1 at the claimed dosage form to treat a vasospastic
disease.” App. Br. 10. Appellants cite Mohrland5 as “fail[ing] to
substantiate earlier reports, including by Clifford, that a 72-hr intravenous
infusion of PGE1 in patients with Raynaud’s syndrome produced clinical
benefit.” Id. at 9 (emphasis omitted). We are not persuaded.
Buyuktimkin discloses that prostaglandin Ei is a vasodilator (FF2) and
that the disclosed composition — which, like the composition recited in the
claims, includes a penetration enhancer, a polysaccharide gum, a lipophilic
compound, and an acidic buffer system (FF1) — is useful to treat peripheral
vascular disease. FF2, FF3. Accordingly, we agree with the Examiner that
tak[ing] the teaching of Buyuktimkin, one having ordinary skill
in the art at the time the invention was made would reasonably
expect that topically applying a semi-solid composition
containing prostaglandin Ei, polysaccharide gum, lipophilic
compound, penetration enhancer and buffer system that is
capable of buffering the composition at a pH of about 3 to
about 7.4 (abstract; column 2, lines 9-28) to a patient’s skin
would keep blood vessels open as a vasodilator according to the
background disclosure of Buyuktimkin and to provide
prolonged treatment of peripheral vascular disease and other
diseases treated with prostaglandin El (see column 1, lines 27-
29; column 8, lines 6-8).
Final Act. 6.
Ischemia may result from vasospasm, a constriction of the blood
vessels. FF9. While Buyuktimkin does not use the word “ischemia,”
prostaglandin Ei is a vasodilator known to maintain open blood vessels.
5 Mohrland et al., A Multiclinic Placebo-Controlled, Double-Blind Study of
Prostaglandin Ej in Raynaud’s Syndrom, 44 Annals of Rheumatic Diseases
754—760 (1985) (“Mohrland”). Morhland was cited by the Appellants as
evidence discrediting Clifford. App. Br. 9.
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FF2. The skilled artisan would thus have reasonably expected to be able to
treat ischemia by applying Buyuktimkin’s topical composition to a patient’s
skin.
The Examiner cited Clifford as evidence that administering
Buyuktimkin’s topical composition “would produce the effect [of]
improving tissue ischemia in a skin.” Final Act. 6. Appellants argue that
Mohrland “fails to substantiate” Clifford. App. Br. 9. We are not persuaded
because Clifford is not necessary to our rejection. Moreover, balancing the
weight of Mohrland’s inability to substantiate Clifford’s report that
intravenous administration of prostaglandin Ei produced significant clinical
benefit in patients with Raynaud’s syndrome against Buyuktimkin’s
subsequent disclosure of a topical composition (FF1) with advantageous
properties (FF7, FF8) that is useful to maintain open blood vessels (FF2) and
treat peripheral vascular disease (FF2, FF3), we find that a preponderance of
the evidence supports that the skilled artisan would reasonably have
expected to be able to treat ischemia by applying Buyuktimkin’s topical
composition to a patient’s skin.
Double Patenting
Appellants argue all of the double patenting rejections together. App.
Br. 10—11. As the same issue is dispositive with respect to all of the
Examiner’s double patenting rejections, we address them all together.
The full extent of Appellants’ double patenting argument is to
summarily paraphrase the claims applied,6 and then assert “[a]s is apparent,
6 For example, Appellants summarize the applied claims of three reference
patents as follows: “US Patent Nos. 6,486,207; 6,825,234 and 6,323,241
claim methods for ameliorating and/or treating female sexual arousal
disorder and/or erectile dysfunction.” App. Br. 11.
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none of the cited claims suggest present claim 65.” App. Br. 11. No further
exposition is provided. Appellants’ arguments are insufficient to properly
raise an issue on appeal. In reLovin, 652 F.3d 1349, 1357 (Fed. Cir. 2011)
(“[T]he Board reasonably interpreted Rule 41.37 to require more substantive
arguments in an appeal brief than a mere recitation of the claim elements and
a naked assertion that the corresponding elements were not found in the
prior art. Because Lovin did not provide such arguments, the Board did not
err in refusing to separately address claims 2-15, 17-24, and 31-34.”).
Accordingly, we affirm the Examiner’s rejection of claims 65—76 on
the ground of nonstatutory double patenting as being unpatentable over
claims 1—27, 1—29, 1—37, 1—18, 1—31, and 1—32 ofU.S. Patent Nos.
6,046,244, 6,414,028 Bl, 7,105,572 B2, 6,486,207 B2, 6,825,234 B2, and
6,323,241 Bl.
SUMMARY
For these reasons and those set forth in the Examiner’s Answer, and
the Final Office Action, we affirm each of the Examiner’s rejection of
claims 65—76 on the grounds of nonstatutory obviousness-type double
patenting over claims 1—27, 1—29, 1—37, 1—18, 1—31, and 1—32 ofU.S.
Patent Nos. 6,046,244, 6,414,028 Bl, 7,105,572 B2, 6,486,207 B2,
6,825,234 B2, and 6,323,241 Bl.
For the reasons set forth herein, we reverse the Examiner’s rejection
of claims 65—76 under 35 U.S.C. § 103(a) as obvious over Buyuktimkin as
evidenced by Clifford.
For the reasons set forth herein, we enter a new ground of rejection for
claims 65—76 under 35 U.S.C. § 103(a) over Buyuktimkin.
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TIME PERIOD FOR RESPONSE
This decision contains a new ground of rejection pursuant to
37 C.F.R. § 41.50(b). Section 41.50(b) provides “[a] new ground of
rejection pursuant to this paragraph shall not be considered final for judicial
review.” Section 41.50(b) also provides:
When the Board enters such a non-final decision, the appellant,
within two months from the date of the decision, must exercise
one of the following two options with respect to the new ground
of rejection to avoid termination of the appeal as to the rejected
claims:
(1) Reopen prosecution. Submit an appropriate
amendment of the claims so rejected or new Evidence relating to
the claims so rejected, or both, and have the matter reconsidered
by the examiner, in which event the prosecution will be
remanded to the examiner. The new ground of rejection is
binding upon the examiner unless an amendment or new
Evidence not previously of Record is made which, in the opinion
of the examiner, overcomes the new ground of rejection
designated in the decision. Should the examiner reject the claims,
appellant may again appeal to the Board pursuant to this subpart.
(2) Request rehearing. Request that the proceeding be
reheard under §41.52 by the Board upon the same Record. The
request for rehearing must address any new ground of rejection
and state with particularity the points believed to have been
misapprehended or overlooked in entering the new ground of
rejection and also state all other grounds upon which rehearing
is sought.
Further guidance on responding to a new ground of rejection can be
found in the MPEP § 1214.01.
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No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(1). See 37 C.F.R.
§§ 41.50(f), 41.52(b).
AFFIRMED; 37 C.F.R, $ 41.50(b)
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