Ex Parte Vejarano Restrepo

Patent Trial and Appeal Board

Nov 7, 2018

13553615 (P.T.A.B. Nov. 7, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
13/553,615 07/19/2012
20995 7590 11/09/2018
KNOBBE MARTENS OLSON & BEAR LLP
2040 MAIN STREET
FOURTEENTH FLOOR
IRVINE, CA 92614
FIRST NAMED INVENTOR
Luis Felipe Vejarano Restrepo
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.
LFV.OOlA 2951
EXAMINER
HUANG, GIGI GEORGIANA
ART UNIT PAPER NUMBER
1613
NOTIFICATION DATE DELIVERY MODE
11/09/2018 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):
j ayna.cartee@knobbe.com
efiling@knobbe.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte LUIS FELIPE VEJARANO RESTREPO
Appeal 2017-011478 1
Application 13/553,615
Technology Center 1600
Before RICHARD M. LEBOVITZ, MICHAEL J. FITZPATRICK, and
JOHN E. SCHNEIDER, Administrative Patent Judges.
LEBOVITZ, Administrative Patent Judge.
DECISION ON APPEAL
This appeal involves claims directed to an ophthalmic formulation.
The Examiner rejected the claims under 35 U.S.C. § 103 as obvious.
Appellant appeals the Examiner's determination that the claims are
unpatentable. We have jurisdiction under 35 U.S.C. § 6(b). The§ 103
rejections are affirmed.
STATEMENT OF THE CASE
Claims 1, 4---6, 9, 11, and 12 stand finally rejected by the Examiner as
follows:
1 The Appeal Brief ("Br.") identifies Luis Felipe Vejarano Restrepo as the
real-party-in-interest.
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1. Claims 1 and 4--6 under pre-AIA 35 U.S.C. § I03(a) as obvious in
view of Abad (U.S. Pat. Pub. 2014/0200211 Al, published July 17, 2014)
and Kaufman (U.S. Pat. Pub. 2011/0152274 Al, published June 23, 2011).
Ans. 2.
2. Claims 1 and 4--6 under pre-AIA 35 U.S.C. § I03(a) as obvious in
view of Kaufman. Ans. 4.
3. Claim 1 under pre-AIA 35 U.S.C. § I03(a) as obvious in view of
Lubkin (U.S. Pat. 5,041,434, issued Aug. 20, 1991). Ans. 5.
4. Claims 4 and 5 under pre-AIA 35 U.S.C. § I03(a) as obvious in
view of Lubkin and Conway (U.S. Pat. 4,902,696, issued Feb. 20, 1990).
Ans. 6.
5. Claim 6 under pre-AIA 35 U.S.C. § I03(a) as obvious in view of
Lubkin and Boldrini (WO 00/64425, published Nov. 2, 2000). Ans. 7.
6. Claims 9, 11, and 12 under pre-AIA 35 U.S.C. § I03(a) as obvious
in view ofLubkin and York (U.S. Pat. 5,192,780, issued Mar. 9, 1993).
Ans. 7.
A declaration under 37 C.F.R. § 1.132 by the sole inventor, Luis
Felipe Vejarano Restrepo ("Restrepo Deel."), M.D., dated September 25,
2015, was submitted with the Response to the Office Action dated
September 28, 2015 and is relied upon in this Appeal by Appellant.
Claim 1, the only independent claim on appeal, is reproduced below:
1. An ophthalmic formulation comprising an effective amount
of pilocarpine or a pharmaceutically acceptable salt thereof,
phenylephrine or a pharmaceutically acceptable salt thereof,
and naphazoline or a pharmaceutically acceptable salt
thereof.
App. Br. 9 (Claims Appendix).
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1. REJECTION BASED ON ABAD AND KAUFMAN
Findings of Fact ("FF'')
The following findings of fact are pertinent to the rejection:
Abad
FF 1. Abad teaches a composition for treating presbyopia, mild
hyperopia, and irregular astigmatism. Abad, Abstract.
FF2. The composition includes 1) a cholinergic agent and 2) an
alpha-stimulant agonist having an imidazoline group or a non-steroidal anti-
inflammatory agent (NSAID) having COX-2 selectivity. Abad ,r 11.
FF3. Among the list of cholinergic agents (muscarinic acetylcholine
receptor M3 agonists) disclosed by Abad is pilocarpine. Abad ,r 11.
FF4. Among the list of alpha-stimulant agonists having an
imidazoline group disclosed by Abad is naphazoline. Abad ,r 11.
FF5. Abad discloses a composition comprising pilocarpine and
naphazoline. Abad ,r 41.
Kaufman
FF6. Kaufman teaches a composition "to create optically beneficial
miosis to, for example, temporarily treat presbyopia." Kaufman, Abstract.
FF7. The composition comprises 1) one or more
parasympathomimetic drugs or cholinesterase inhibitors and 2) "one or more
alpha agonists" or antagonists. Kaufman, Abstract.
FF8. Kaufman describes one embodiment in which the 1)
parasympathomimetic is pilocarpine and the 2) alpha agonist is brimonidine.
Kaufman ,r 1 7.
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FF9. Kaufman defines an alpha agonist as a compound that stimulates
"both alphal and alpha2" adrenoceptors. Kaufman ,r 24.
FFlO. Among the list of alpha agonists disclosed by Kaufman is
naphazoline and phenylephrine. Kaufman ,r 24.
FF 11. In claim 2 of Kaufman, the alpha agonist is brimonidine or
naphazoline.
Discussion
The Examiner found Abad discloses a composition for treating
presbyopia that comprises pilocarpine and naphazoline as required by claim
1. Final Act. 4; FF3-FF5. The Examiner found that Abad does not disclose
that the composition comprises phenylephrine as required by claim 1. Final
Act. 4. However, the Examiner found that Kaufman discloses a composition
for treating presbyopia, the same indication described by Abad, in which the
composition comprises the exemplified pilocarpine and one or more alpha
agonists of which naphazoline and phenylephrine appear in a list. Id. at 4--5;
FFl, FF6.
The Examiner determined it would have been obvious to one of
ordinary skill in the art to have incorporated phenylephrine into Abad's
composition because it was taught for the same purpose by Kaufman. Final
Act. 5.
Appellant argues that phenylephrine is a well-known mydriatic - a
compound that induces dilation of the pupil - which would have been
expected "to cancel out miosis", the constriction of the pupil of the eye
"produced by pilocarpine." Br. 5. Appellant contends that, for this reason,
"a person of ordinary skill in the art would not have been motivated to add
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phenylephrine to a formulation containing pilocarpine for temporarily
treating, ameliorating, or reducing presbyopia." Id.
This argument does not persuade us that the Examiner erred. Despite
Appellant's contention that phenylephrine would have the opposite effect of
pilocarpine, phenylephrine is expressly disclosed as a useful alpha
adrenergic receptor drug by Kaufman to treat the same indication as Abad
(FF 1, FF6), and in combination with a parasympathomimetic drug, such as
the preferred pilocarpine. 2 FF8, FF9, FFIO.
Appellant makes a similar argument for Abad, arguing that Abad
teaches utilizing alpha-2 adrenergic agonists, such as brimonidine and
naphazoline, which constrict the pupil, while phenylephrine is an alpha- I
agonist, which dilates it. Br. 5.
While it is true that Abad discloses these apparently opposing effects
of alpha- I and alpha-2 agonists (Abad ,r 5), Kaufman contains an express
teaching that phenylephrine is useful to treat presbyopia. FFIO. The fact
that it appears in a list of other alpha adrenergic agonists does not detract
from this teaching. Rather, the list of compounds are expressly disclosed as
suitable alpha agonists, indicating that Kaufman believed all such drugs in it
are efficacious for treating the identified eye disorder. Appellant has not
provided adequate objective scientific evidence that outweighs the explicit
2 Appellant did not address the issue of combining pilocarpine and
phenylephrine in the declaration by inventor Luis Felipe Vejarano Restrepo,
M.D. We note that Appellant discloses several publications which describe
the application of pilocarpine and phenylephrine to the eye, including,
Mapstone, British J. of Opthalmol., 1977, 61:510-511; Tabandeh et al., Eye,
1995, 9:452-455.
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disclosure in Kaufman of utilizing one or more alpha agonists to treat
presbyopia, where the list of drugs includes phenylephrine. An argument
made by counsel in a brief does not substitute for evidence lacking in the
record. Estee Lauder, Inc. v. L 'Orea!, S.A., 129 F.3d 588, 595 (Fed. Cir.
1997). Thus, Appellant has not established a lack of a reasonable
expectation of success by objective scientific evidence.
Appellant also argues that Kaufman teaches "that brimonidine
potentiates the effect of pilocarpine on the pupil" and that, in view of this
teaching, "a person of ordinary skill in the art would have only been
motivated to try other alpha agonist[ s] that may potentiate the effect of
pilocarpine on the pupil." Br. 5.
This argument is not persuasive. Kaufman has explicit disclosure that
the alpha agonist can be brimonidine or naphazoline (FF 10, FF 11 ), both of
which are alpha-agonists having an imidazoline group. Because pilocarpine
is preferred by Kaufman (FF8), one of ordinary skill in the art would have
had reason to combine it with either brimonidine or naphazoline since both
are described as suitable by Kaufman.
Moreover, with regard to Appellant's argument about the potentiation
of pilocarpine by brimonidine (Br. 5), Abad contains a broader teaching that
other alpha agonists could potentiate the action of pilocarpine:
The compositions of the present invention were surprisingly
and unexpectedly found to potentiate the action of and decrease
the side effects of a cholinergic agent such as pilocarpine, such
that a cholinergic agent can be effectively used in combination
with an alpha-stimulant agonist having an imidazoline group or
a non-steroidal anti-inflammatory agent (NSAID) having COX-
2 selectivity to contract the ciliary and pupillary sphincter
muscles for treating ocular conditions, such as presbyopia ...
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without the patient experiencing the undesirable side effects
normally associated with pilocarpine therapy.
Abad ,r 12 (emphasis added).
In sum, we are persuaded by the evidence that the Examiner
established that claim 1 is primafacie obvious in view of Abad and
Kaufman.
Declaration
Appellant provided a declaration by inventor Luis Felipe Vejarano
Restrepo, M.D. to establish the nonobviousness of the claimed subject
matter. The declaration is said by Appellant to show surprising and
unexpected results compared to other ophthalmic formulation containing
pilocarpine, establishing the nonobviousness of the claimed invention. Br.
7.
A showing of "unexpected results" can be used to demonstrate the
non-obviousness of the claimed invention. In re Soni, 54 F.3d 746, 750
(Fed. Cir. 1995) ("One way for a patent applicant to rebut aprimafacie case
of obviousness is to make a showing of 'unexpected results,' i.e., to show
that the claimed invention exhibits some superior property or advantage that
a person of ordinary skill in the relevant art would have found surprising or
unexpected.")
Dr. Restrepo states that "one drop of a formulation containing 0.26°/o
pilocarpine, 0.50°/o phenylephrine, and 0.003°/o naphazoline
(Formulation A)" ( emphasis added) was administered to patients to test its
efficacy in treating presbyopia. Deel. ,r 11. Dr. Restrepo states that near
vision improved with Formulation A, while far vision was not adversely
affected as might have been expected "due to miosis caused by pilocarpine."
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Id. Furthermore, Dr. Restrepo stated "The fact that effectiveness of
Formulation A remained after 1 month of administering only one drop was
unexpected and surprising." Id.
Dr. Restrepo also compared Formulation A to:
1) one drop of a formulation containing 0.25°/o pilocarpine, and one
drop of a formulation containing 0.2 °/o brimonidine ( which he referred to as
the "Kaufman formulation"); and
2) one drop of a formulation that contains 1 °/o pilocarpine and
0.025°/o oxymetazoline (which he referred to as the "Abad formulation").
Kaufman
With respect to the "Kaufman formulation," Dr. Restrepo stated that
Figure 3 of his declaration showed that "Formulation A not only resulted in
a greater improvement in the near vision compared to the Kaufman
formulation; Formulation A also achieved a longer lasting efficacy."
Restrepo Deel. § 12. Dr. Restrepo concluded: "Compare[d] to Kaufman
formulation, which contains about the same amount of pilocarpine,
Formulation A was able to achieve better near visual acuity. Furthermore,
Formulation A retained a longer lasting effect on near visual acuity - for at
least one month." Id. at ,r 13.
Abad
With respect to the "Abad formulation," Dr. Restrepo states:
The Abad formulation seems to have a very similar effect on
the near vision compared to Formulation A. However, Abad
formulation contains 1 % pilocarpine, while Formulation A
contains only 0.26% pilocarpine, which is close to quarter of
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the amount of pilocarpine in Abad formulation. Figure 4 below
shows the overlay plots of changes in far UCV A following
administration of Formulation A and Abad formulation. The
Abad formulation was unable to avoid the adverse effect of
decreasing far vision.
Restrepo Deel. ,r 12.
Dr. Restrepo concluded that "Compare[d] to Abad formulation,
Formulation A was able to achieve similar results for the first 5 hours with
about a quarter of the pilocarpine. In addition, Formulation A also improved
the far visual acuity while Abad formulation decreased it." Id. at ,r 13.
Analysis
We agree with the Examiner that Appellant's showing of unexpected
results is not commensurate with the full scope of the claim. As discussed
by the Examiner, claim 1 is unrestricted as to the amount of each of
pilocarpine, phenylephrine, and naphazoline present in the ophthalmic
formulation, but only one concentration of each drug was tested by Dr.
Restrepo. Ans. 10. When unexpected results are proffered by an appellant
to rebut a prima facie case of obviousness, the appellant must "provide[] an
adequate basis to support the conclusion that other embodiments falling
within the claim will behave in the same manner" in order to "establish that
the evidence is commensurate with [the] scope of the claims." In re Kao,
639 F.3d 1057, 1068 (Fed. Cir. 2011). One data point is insufficient "to
ascertain a trend in the exemplified data which would allow [ one having
ordinary skill in the art] to reasonably extend the probative value thereof."
In re Kollman, 595 F.2d 48, 56 (CCPA 1979). Consequently, we find the
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evidence inadequate to establish unexpected results for the claim's full
scope.
To establish unexpected results, the claimed subject matter must be
compared with the closest prior art. 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"). Abad has an example of pilocarpine and
naphazoline, the same two drugs recited in claim 1. FF5. However, the only
comparison made in the declaration is with pilocarpine and oxymetazoline.
Consequently, the comparison should have been between the claimed
subject matter and Abad's example of pilocarpine and naphazoline.
Accordingly, for the reasons set forth above, we conclude that the
showing provided by Appellant is insufficient, when the evidence is
considered anew, to establish the non-obviousness of claim 1 based on Abad
and Kaufman.
Conclusion
The obviousness rejection of claim 1 based on Abad and Kaufman is
affirmed. Claims 4--6 were not separately argued and fall with claim 1. 37
C.F.R. § 4I.37(c)(l)(iv).
2. OBVIOUSNESS BASED ON KAUFMAN
The Examiner rejected the composition of claim 1 comprising
pilocarpine, phenylephrine, and naphazoline as obvious based on Kaufman.
Final Act. 6; Ans. 4. The Examiner found that Kaufman discloses a
composition for treating presbyopia in which the composition comprises the
exemplified pilocarpine, a parasympathomimetic drug, and one or more
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alpha agonists, which include the claimed naphazoline and phenylephrine in
a list of compounds. Final Act. 6-7. The Examiner found that Kaufman
teaches that the parasympathomimetic drug can be combined with "one or
more alpha agonists," making it obvious to have selected naphazoline and
phenylephrine from the list of drugs described as suitable for treating
presbyopia. Id. at 7.
Appellant argues that there would have been a lack of a reasonable
expectation of success "in view of the mydriatic effect [ dilation of the pupil]
of phenylephrine [alpha-I agonist] and the Kaufman's emphasis on selecting
alpha-2 agonist for the ophthalmic composition." Br. 6. While it is true that
Kaufman exemplifies brimonidine, an alpha-2 agonist, Kaufman expressly
discloses that "alphal and alpha2" adrenoceptor agonists are suitable for its
composition and expressly lists phenylephrine as an example of one. FF9,
FFIO. Appellant did not provide adequate evidence or scientific reasoning
as to why one of ordinary skill in the art would have not have selected these
two alpha agonists for the purposes described in Kaufman. See also
discussion above under Abad and Kaufman rejection,
Appellant also argues the claimed subject matter exhibits unexpected
results over Kaufman. Br. 6-7. However, for the reasons already discussed,
we find the results insufficient to establish nonobviousness of the full scope
of claim 1. Consequently, the rejection of claim 1 as obvious in view of
Kaufman is affirmed. Claims 4---6 were not separately argued and fall with
claim 1. 37 C.F.R. § 4I.37(c)(l)(iv).
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3. OBVIOUSNESS BASED ON LUBKIN
The Examiner rejected the composition of claim 1 comprising
pilocarpine, phenylephrine, and naphazoline as obvious based on Lubkin.
Final Act. 9; Ans. 5. The Examiner cited the following disclosure from
Lubkin:
D. 17-beta Estradiol or its water soluble derivatives combined
with one or more of the following active ingredients for the
purpose of treating associated ophthalmologic conditions in
conjunction with dry eye syndrome:
1. Anti-infectives: gentamicin sulfate, neomycin sulfate,
sulfacetamide sodium, chloramphenicol
2. Anti-inflammatory: dexamethasone, dexamethasone
phosphate, prednisolone, prednisolone phosphase
3. Antiviral: idoxuridine
4. Antihistamine: naphazoline HCl
5. Cycloplegic: tropicamide, atropine sulfate
6. Local anesthetics: proparacaine, lidocaine
7. Miotics: pilocarpine
8. Vasoconstrictors: phenylephrine HCl
Lubkin 4:33--49 (emphasis added).
As found by the Examiner, Lubkin discloses all three drugs recited in
claim 1, making their selection obvious to one of ordinary skill in the art.
Final Act. 10.
Appellant contends that Lubkin teaches that the composition is for
treating dry eye, and not for ameliorating or treating presbyopia. Br. 7.
Appellant states that "A person of ordinary skill in the art trying to develop
an ophthalmic formulation for ameliorating presbyopia would not have been
motivated to specifically combine these three active ingredients." Id. This
argument is not persuasive because claim 1 is directed to a composition and
the composition is not limited to treating a specific ophthalmic disorder.
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Appellants also argue the claimed subject matter exhibits unexpected
results over Lubkin. Br. 7. However, for the reasons already discussed, we
find the results insufficient to establish nonobviousness of the full scope of
claim 1. Appellant did not separately address Lubkin in Dr. Restrepo's
declaration. Consequently, the rejection of claim 1 as obvious in view of
Lubkin is affirmed.
4, 5, 6. OBVIOUSNESS REJECTIONS BASED ON LUBKIN AND
CONWAY, BOLD RINI, OR YORK
Claims 4, 5, 6, 9, 11, and 12 are rejected by the Examiner as obvious
in view of Lubkin combined with Conway, Boldrini, or York. Appellant
states that neither Conway, Boldrini, nor York "cure the defect ofLubkin."
Br. 8. As we find the arguments against Lubkin to be unavailing, we affirm
Rejection 4, 5, and 6 for the same reasons as for Lubkin.
Appellant also argues the claimed subject matter exhibits unexpected
results over Lubkin. Br. 7. However, for the reasons already discussed, we
find the results insufficient to establish nonobviousness of the full scope of
claim 1. As noted, Appellant did not address Lubkin in Dr. Restrepo' s
Declaration.
The rejections of claims 4, 5, 6, 9, 11, and 12 as obvious is affirmed.
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)(l)(iv).
AFFIRMED
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