Ex Parte Jeon et al

Patent Trial and Appeal Board

Feb 1, 2019

14129705 (P.T.A.B. Feb. 1, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
14/129,705 03/28/2014
21125 7590 02/05/2019
NUTTER MCCLENNEN & FISH LLP
SEAPORT WEST
155 SEAPORT BOULEVARD
BOSTON, MA 02210-2604
FIRST NAMED INVENTOR
Hong-R yeol Jeon
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.
113926-00015 6769
EXAMINER
BASQUILL, SEAN M
ART UNIT PAPER NUMBER
1613
NOTIFICATION DATE DELIVERY MODE
02/05/2019 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):
docket@nutter.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte HONG-RYEOL JEON, DO-WOO KWON, BONG-SANG LEE,
SEONG-SHIN KW AK, SUN-AHE LEE, HYIN-JUNG PARK,
and JEONG-HWA Y00 1
Appeal2018-000496
Application 14/129,705
Technology Center 1600
Before FRANCISCO C. PRATS, JOHN E. SCHNEIDER, and
RACHEL H. TOWNSEND, Administrative Patent Judges.
SCHNEIDER, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal2 under 35 U.S.C. § 134 from the Examiner's
rejection of claims to pharmaceutical compositions which have been rejected
as obvious. We have jurisdiction under 35 U.S.C. § 6(b ).
We AFFIRM.
1 Appellants identify the Real Party in Interest as CTC Bio, Inc. Br. 3.
2 We have considered and herein refer to the Specification of Dec. 27, 2013
("Spec."); Final Office Action of July 8, 2016 ("Final Act."); Appeal Brief
of Nov. 29, 2016 ("Br."); and Examiner's Answer of Dec. 22, 2016
("Ans.").
Appeal2018-000496
Application 14/129,705
STATEMENT OF THE CASE
"Premature ejaculation is one of the common sexual complaints and is
estimated to affect approximately 3 0 to 40% of men." Spec. 1.
It is known that premature ejaculation may be treated by
using antidepressants comprising fluoxetine, paroxetine or
sertraline. However, the antidepressants cause side effects such
as nausea, headache, dizziness, asomnia, xerostama and
anxiety, and side effect associated with sedation,
anticholinergic actions and cardiovascular responses. Also,
considering that the antidepressants affect the nervous system,
it is necessary to finely control their dosages to ensure safety.
That is, unlike other drugs, since a drug for improving
premature ejaculation affect[s] the cardiovascular system and/or
the nervous system which may cause severe side effects, its
dosage must be carefully controlled.
Spec. 1-2.
The Specification describes "a pharmaceutical composition for
treating premature ejaculation, which can be conveniently taken just prior to
sexual activity, not for a certain period of time, to provide rapid-onset of
efficacy and exhibit outstanding effectiveness for premature ejaculation."
Spec. 2.
Claims 1, 3, 4, 7-9, and 13-19 are on appeal. Claim 1 is
representative and reads as follows:
1. A pharmaceutical composition for oral administration
configured to treat, prevent or improve premature ejaculation,
the composition being taken on demand prior to sexual activity,
wherein the composition comprises 7 to 13 wt% of
clomipramine hydrochloride in an amount of 15 mg as an active
ingredient, 70 to 80 wt % of lactose, 7 to 13 wt % of
pregelatinized starch and 1 to 5 wt % of sodium starch glycolate
based on the total weight of the composition.
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Application 14/129,705
Claims 1, 3, 4, 7-9, and 13-19 have been rejected under 35 U.S.C.
§ 103(a) as unpatentable over Tam. 3
DISCUSSION
Issue
The issue with respect to this rejection is whether a preponderance of
the evidence supports the Examiner's conclusion that the subject matter of
the claims would have been obvious over Tam.
The Examiner finds that "Tam teaches treating premature ejaculation
by the administration of a composition containing clomipramine less than
four hours prior to engaging in sexual intercourse." Final Act. 4. The
Examiner finds that Tam teaches that the composition containing
clomipramine after being administered should have the desired biological
response take place between 1.5 and 4 hours thereafter. Final Act. 5. The
Examiner finds that Tam teaches the inclusion of excipients such as "lactose
(disclosed as useful as either a carrier, a filler, or as a binder), pregelatinized
starch (disclosed as useful as a binder), polyvinylpyrrolidone (disclosed as
useful as either a disintegrant or as a binder), sodium starch glycolate
( disclosed as useful as a disintegrant ), and magnesium stearate ( disclosed as
useful as a lubricant, optimally in concentrations of no more than 2% of the
composition)." Id. The Examiner finds that Tam exemplifies embodiments
containing from 10mg to 300mg clomipramine and also teaches that the
dosage amount can be varied to achieve the desired outcome. Id. The
Examiner concludes
3 Tam et al., US 6,495,254 B 1, issued Dec. 17, 2002 ("Tam").
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it would have obvious to have selected various combinations of
various disclosed ingredient such as the instantly claimed
combination of 15 mg clomipramine HCl combined with the
claimed concentrations and quantities of each of lactose,
pregelatinized starch, PVP, and sodium starch glycolate from
within a prior art disclosure, to arrive at compositions "yielding
no more than one would expect from such an arrangement."
Final Act. 7.
Appellants contend that Tam does not teach the present invention and
actually teaches away from the claimed invention. Br. 5---6. Appellants
contend that, given that the typical dose of clomipramine is around 125-150
mg a day to treat depression and higher for Obsessive-Compulsive Disorder,
one skilled in the art would have sought to use a dose taught by Tam that
more closely matches "the end of Tam's preferred doses (20-200 mg or 25-
100 mg), closer to the known 125-150 mg therapeutic doses." Br. 7.
Appellants contend that Tam teaches away from the present invention
in that Tam teaches that "oral formulations" are undesirable and that
buccal/immediate release formulations are preferred. Br. 7-8. Appellants
further contend that "Tam does not teach or suggest anything regarding the
claimed oral administration ( e.g., for gastric dissolution)." Br. 8. Appellants
also contend that there is evidence of unexpected results sufficient to
overcome a prima facie case of obviousness. Id.
Appellants contend that Tam does not teach or suggest the amounts of
excipients recited in the claims, specifically the amounts recited in claims 13
and 17-19. Br. 9-10.
Appellants contend that Tam does not teach or suggest the dissolution
rates recited in claims 4, 14, 18, and 19. Br. 10.
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Findings of Fact
We adopt the Examiner's findings as our own, including with regard
to the scope and content of, and motivation to modify the prior art. Final
Act. 4--7. The following findings are included for emphasis and reference
purposes.
FFl. Tam discloses "methods and pharmaceutical compositions for
treating sexual dysfunction; more particularly, the invention relates to
treatment of premature ejaculation, preferably by on demand administration
of clomipramine or a pharmacologically acceptable acid addition salt
thereof." Tam col. 1, 11. 7-11.
FF2. Tam teaches that the pharmaceutical formulation "is
administered less than four hours before engaging in sexual activity." Tam.
col. 2, 11. 61---64.
FF3. Tam teaches "It is yet a further object of the invention to
provide such a method wherein the pharmaceutical formulation is
administered orally." Tam col. 3, 11. 1-3 (emphasis added).
FF4. Tam teaches
It is another object of the invention to provide a dosage
form for delaying the onset of ejaculation in a male individual,
comprising a rapid-release formulation for systemic absorption
containing an amount of an active agent selected from the group
consisting of clomipramine and pharmacologically acceptable
acid addition salts thereof effective to delay the onset of
ejaculation by the individual during sexual activity.
Tam col. 3, 11. 14--21 (emphasis added).
FF5. Tam teaches "Drug delivery may be accomplished through any
route that will provide appreciable systemic levels of clomipramine effective
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to delay the onset of ejaculation. Thus, drug delivery may be effected by,
but not limited to, oral, parenteral, buccal or pulmonary administration."
Tam col. 3, 11. 33-37. (emphasis added).
FF6. Tam teaches "[t]he pharmaceutical dosage form may be any
dosage form suitable for systemic absorption and may be, but is not limited
to, rapidly disintegrating tablets, effervescent tablets, sublingual tablets,
buccal dosage forms, sublingual sprays, gum formulations or inhalers." Tam
col. 3, 11. 55---60.
FF7. Tam defines "rapidly disintegrating" to mean
a tablet that dissolves or disperses in [a] manner that allows for
the absorption of the active agent such that "on demand"
administration of the active agent is possible. Thus, many
rapidly disintegrating tablets often, but not necessarily, include
a disintegrant in the tablet formulation or are otherwise
specially designed to quickly disintegrate upon administration.
Tam. col. 5, 11. 5-12.
FF8. Tam teaches
By the term "systemically administered" applicants
intend all non-local modes of administration that result in
appreciable drug levels in an individual's circulatory system.
Thus, a "systemically administered" drug must achieve
sufficient levels in an individual's circulatory system before the
drug is available to exert its intended pharmacological and
therapeutic activity.
Tam col. 4, 11. 34--40.
FF9. Tam teaches
It is preferred that the pharmaceutical formulation is
administered orally, buccally or transmucosally. As will be
appreciated by those skilled in the art, tablets, including
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effervescent tablets and "open matrix network" tablets, are
administered orally. These formulations are absorbed in the
gastrointestinal tract, although some absorption will take place
in the oral mucosa.
Tam col. 12, 11. 3-9 (emphasis added).
FF 10. Tam teaches that the modes of administration taught in Tam
"are not 'local' in nature and will result in systemic levels of the active
agent." Tam col. 12, 11. 23-25.
FF 11. Tam teaches that the unit dosage forms contain the active agent
in a range of from 1 to 300 mg and that the "dosing regimen can be
modulated in order to achieve satisfactory control of the onset of
ejaculation." Tam col. 12, 11. 40-51. Tam exemplifies a number of different
oral formulations with differing amounts of clomipramine hydrochloride
throughout this dosage range. Tam col. 13, 1. IO-col. 15, 1. 22.
FFI2. Example 2 of Tam discloses a formulation containing 10 mg of
clomipramine. Tam col. 13, 11. 30-50.
FF 13. Tam teaches "In addition to the active agent, the formulation,
particularly when present in a gum or oral, buccal or sublingual tablet, will
generally contain other materials such as binders, diluents, lubricants,
disintegrants, fillers, stabilizers, surfactants, coloring agents, taste-masking
agents, and the like." Tam col. 10, 1. 63 - col. 11, 1. 1.
FFI4. Tam teaches
Binders are used to impart cohesive qualities to the formulation;
suitable binder materials include, but are not limited to, starch
(including com starch and pregelatinized starch), gelatin,
sugars (including sucrose, glucose, dextrose and lactose),
polyethylene glycol, waxes, and natural and synthetic gums,
e.g., acacia sodium alginate, polyvinylpyrrolidone, cellulosic
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polymers (including hydroxypropyl cellulose, hydroxypropyl
methylcellulose, methyl cellulose, hydroxyethyl cellulose, and
the like), and Veegum®. As will be appreciated by those skilled
in the art, binders, if present, must not delay disintegration of
the formulation to such an extent that "on demand"
administration is ineffective.
Tam col. 11, 11. 1-12 (emphasis added).
FF15. Tam teaches "For solid compositions, conventional nontoxic
solid carriers include, for example, pharmaceutical grades of mannitol,
lactose, starch, magnesium stearate, sodium saccharin, talc, cellulose,
glucose, sucrose, magnesium carbonate, and the like." Tam col. 6, 11. 41--45
( emphasis added).
FF16. Tam teaches "Disintegrants are used to facilitate disintegration
of the dosage form, and are generally starches, clays, celluloses, algins,
gums or crosslinked polymers; sodium starch glycolate is particularly
preferred." Tam col. 11, 11. 21-24 (emphasis added).
FF 1 7. Tam teaches "For oral administration, the composition will
generally take the form of a tablet or capsule, or may be an aqueous or
nonaqueous solution, suspension or syrup. Tablets and capsules for oral use
will generally include one or more commonly used carriers such as lactose
and com starch." Tam col. 6, 11. 60-64.
Principles of Law
[T]he examiner bears the initial burden, on review of the
prior art or on any other ground, of presenting a prima facie
case ofunpatentability. If that burden is met, the burden of
coming forward with evidence or argument shifts to the
applicant.
After evidence or argument is submitted by the applicant
in response, patentability is determined on the totality of the
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record, by a preponderance of evidence with due consideration
to persuasiveness of argument.
In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992).
"A prima facie case of obviousness typically exists when the ranges of
a claimed composition overlap the ranges disclosed in the prior art." In re
Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003).
"The prior art's mere disclosure of more than one alternative does not
constitute a teaching away from any of these alternatives because such
disclosure does not criticize, discredit, or otherwise discourage the solution
claimed." In re Fulton, 391 F.3d 1195, 1201 (Fed. Cir. 2004).
"To be particularly probative, evidence of unexpected results must
establish that there is a difference between the results obtained and those of
the closest prior art, and that the difference would not have been expected by
one of ordinary skill in the art at the time of the invention." Bristol-Myers
Squibb Co. v. Teva Pharms. USA, Inc., 752 F.3d 967, 977 (Fed. Cir. 2014).
Analysis
We find the Examiner has established that the claims would have been
obvious to one of ordinary skill in the art at the time the invention was made
over Tam. Appellants have not produced evidence showing, or persuasively
argued, that the Examiner's determinations on obviousness are incorrect.
Only those arguments made by Appellants in the Brief have been considered
in this Decision. Arguments not presented in the Brief are waived. See 37
C.F.R. § 4I.37(c)(l)(iv) (2015). We address Appellants' arguments below.
Appellants contend that Tam teaches away from the present invention
in that the formulation asserted by the Examiner to be the "closest prior art"
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to the claimed formulation is a "buccal tablet" containing 10mg of
clomipramine, where the active agent is absorbed directly through the oral
mucosa. Br. 7. According to Appellants, such a formulation teaches away
from the claimed oral formulation because it avoids some of the problems
with oral administration which involves absorption in the gastrointestinal
tract, "e.g. slow absorption, degradation of the active agent by fluids present
in the gastrointestinal tract and/or first-pass inactivation in the liver. Id.
Appellants contend that this teaching "disparaging 'oral modes of
administration"' would lead one skilled in the art away from the claimed
composition. Id.
We have considered Appellants' arguments and are unpersuaded.
Tam indicates that a buccal tablet is "[ o ]ne type of tablet [ for oral
administration] that provides rapid release" of the active, and notes that
buccal drug delivery avoids disadvantages encountered with other oral
modes of administration. Tam col. 7, 11. 6-18. And Tam exemplifies a
buccal tablet formulation. FF12. While Tam does teach there are
advantages of buccal administration, Tam clearly teaches that the active
agent can be administered orally for absorption by the gastrointestinal tract.
FF3, 5, and 9. While oral administration may not be the most preferred
route in Tam, we do not find that Tam criticizes, discredits, or discourages
the use of oral administration such that one skilled in the art would not use
oral administration.
Appellants next argue that one skilled in the art would be led by the
teachings of Tam to use significantly higher amounts of clomipramine than
the amount recited in the claims. Br. 7. Appellants argue that the typical
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amounts of clomipramine administered to treat depression and OCD range
from 20 to 200 mg and that one skilled in the art would use this range as a
base for developing a treatment for premature ejaculation. Id. Appellants
argue that Tam does not teach or suggest using lower dosages and that one
skilled in the art would not have a reasonable expectation of success in using
a lower amount of active agent. Br. 7-8.
Again we are not persuaded by Appellants' arguments. Tam teaches
that clomipramine may be present in the dosage form in an amount ranging
from 1 to 300 mg. FF 11. The amount of clomipramine hydrochloride
required by the claims, i.e., 15 mg, falls within this range making the amount
obvious. In re Peterson, 315 F.3d at 1329. In addition, Example 2 of Tam
discloses a formulation that includes 10 mg of clomipramine. FF12. And
Tam teaches that such a formulation "is expected to be effective in treating
premature ejaculation" as are the other prepared formulations described in
Tam. Tam, col. 16, 11. 7-8. In light of these teachings, we disagree with
Appellants that one of ordinary skill "in the art would have selected from the
end of Tam's preferred doses (20-200 mg or 25-100 mg), closer to the
known 125-150 mg therapeutic doses." Br. 7. Rather, Tam's teachings
would lead one skilled in the art to consider a formulation that includes an
amount at the low end of the 1 to 300 mg range. In addition, as pointed out
by the Examiner, the art teaches that the "side effect profile of clomipramine
is dose dependent." Ans. 7-8. Tam teaches that the "dosing regimen can be
modulated in order to achieve satisfactory control of the onset of
ejaculation." FF. 11. We find that the teachings of the art would lead one
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skilled in the art to use the lowest possible does that still yielded the desired
effect.
Appellants argue that there is evidence of unexpected results which
overcomes a prima facie case of obviousness. Br. 8. In support of this
contention, Appellants offer the declaration of the inventors 4 and a clinical
trial report5 attached to the declaration. Id. The Report purports to show
that the claimed composition exhibits improved performance with reduced
side effects. Br. 8, Deel. ,r 16.
We have considered Appellants' arguments, the declaration, and the
Report and find them unpersuasive. The study discussed in the report
compared the effectiveness of a composition containing 15 mg. of
clomipramine against a placebo. Report 8. As the Examiner points out, it
does not compare the claimed composition with the closest prior art, Tam
that includes 10 mg of clomipramine to be given by mouth for treatment of
premature ejaculation. Ans. 7. Thus the data and the declarant testimony
concerning this data are insufficient to overcome a rejection for obviousness.
Appellants contend that Tam does not disclose the amounts of
excipients recited in the claims, especially the amounts recited in claims 13
and 17-19. Br. 9. Appellants argue that Tam does not disclose the general
4 Declaration ofB. Lee, Ph.D., D. Kwon, Ph.D., and H. Jeon, Ph.D. Under
37 C.F.R. 1.132, filed May 11, 2016 ("Deel.").
5 Clinical Study Report, A Randomized, Double-Blind, Placebo-controlled,
Fixed dose, Parallel Grouped, Multicenter Clinical Study to Evaluate the
Safety and Efficacy of P ED-1 in Male Patients with Premature Ejaculation,
CSR No. CTC-PE-01 v 1.1 (Aug. 27, 2012) ("Report"). We note that
Appellants have only provided selected pages of the report.
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conditions of the subject matter of the claims and that the specific amounts
would not be arrived at by routine experimentation. Id. Appellants argue
that Tam discloses a laundry list of excipients and is nothing more than an
invitation to experiment. Id. Appellants also contend that drug formulation
is challenging and unpredictable and that developing the claimed
formulation would not have been obvious. Br. 9.
Appellants' arguments are unpersuasive. Tam does not disclose a
laundry list of excipients but lists a few specific examples of carriers ( 10
including lactose), binders (17 including lactose and pre-gelatinized starch)
and disintegrants (7 with sodium starch glycolate preferred). Tam also
teaches that lactose is one of two commonly used carriers for oral
formulations. FF 17. Thus the list of excipients is finite and specifically
teaches the recited excipients. FF 13-17. "Reading a list and selecting a
known compound to meet known requirements is no more ingenious than
selecting the last piece to put into the last opening in a jig-saw puzzle. It is
not invention." Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S.
327, 335 (1945); see also Merck & Co. Inc. v. Biocraft Laboratories, Inc.,
874 F.2d 804, 807 (Fed. Cir. 1989). In addition, Tam describes the action of
the different excipients and teaches that the level of binder should be such
that it does not interfere with the disintegration of the formulation. FF 13-
16. We find that Tam provides sufficient guidance to one skilled in the art
to modify the teachings of Tam to produce a composition encompassed by
Appellants' claims.
Appellants also contend that Tam does not teach or suggest the
specific dissolution rates recited in claims. Br. 10. Appellants contend that
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the open matrix formulation cited by the Examiner is designed to
disintegrate in the mouth. Id. Appellants contend that the formulation
disclosed in Tam is unrelated to the formulation of the claims in that the
formulation in the claims is directed to gastric not oral dissolution. Id.
We remain unpersauded. The claims are silent about where
dissolution occurs; rather they at most only specify the conditions of a
dissolution test. See, e.g., claim 4, Br. 11 (Claims App'x). In addition, Tam
teaches that oral compositions, which are contemplated as part of the
invention of Tam, including open matrix formulations that are designed for
gastric absorption. FF9. Tam also teaches that the disclosed formulations
are designed for rapid dissolution or disintegration to ensure rapid release of
the formulation. FF4-7. Thus, while Tam does not recite any specific
dissolution rate, we agree with the Examiner that Tam's teachings of a rapid
disintegration rate would have lead one skilled in the art to have developed a
formulation meeting the ranges recited in the claims. Ans. 9.
Conclusion of Law
We conclude that a preponderance of the evidence supports the
Examiner's conclusion that the subject matter of the claims would have been
obvious over Tam.
SUMMARY
We affirm the rejection of claims 1, 3, 4, 7-9, and 13-19 under 35
U.S.C. § 103(a).
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TIME PERIOD FOR RESPONSE
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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