Ex Parte Nagano et al

Patent Trial and Appeal Board

Feb 16, 2018

13688659 (P.T.A.B. Feb. 16, 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.
13/688,659 11/29/2012 Atsuhiro NAGANO 24933Y 5010
34375 7590 02/21/2018
NATH, GOLDBERG & MEYER
Joshua Goldberg
112 South West Street
Alexandria, VA 22314
EXAMINER
MCMILLIAN, KARA RENITA
ART UNIT PAPER NUMBER
1627
NOTIFICATION DATE DELIVERY MODE
02/21/2018 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):
USPTO@nathlaw.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte ATSUHIRO NAGANO, YOSHIHISA NISHIBE, and
KAZUYA TAKANASHI
Appeal 2016-004518
Application 13/688,659
Technology Center 1600
Before DEMETRA J. MILLS, RICHARD M. LEBOVITZ, and
RYAN H. FLAX, Administrative Patent Judges.
MILLS, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35U.S.C. § 134. The Examiner has rejected
the claims for obviousness. We have jurisdiction under 35 U.S.C. § 6(b).
We affirm.
Appeal 2016-004518
Application 13/688,659
STATEMENT OF CASE
Ciclesonide is an anti-inflammatory glucocorticoid. According to the
Specification, an “object of the present invention is to provide a ciclesonide
aqueous pharmaceutical composition that avoids variations in ciclesonide
concentration during production as well as decreases in the ciclesonide
recovery rate.” Spec. 3.
The following claims are representative of the appealed subject matter.
15. An aqueous pharmaceutical composition which comprises
ciclesonide, crystalline cellulose carmellose sodium and hydroxypropyl-
methylcellulose, wherein said crystalline cellulose carmellose sodium
concentration is 1.7% w/w, and wherein said hydroxypropyl-methylcellulose
concentration is from 0.1 % w/w to 0.5% w/w, relative to the total amount of
the composition.
16. An aqueous pharmaceutical composition according to claim 15,
which further comprises one or more types of a water-insoluble substance
and/or water-low soluble substance which is one or more types of cellulose.
29. An aqueous pharmaceutical composition according to claim 15,
further comprising at least one osmotic-pressure controlling agent.
Cited References
Karlsson WO 99/25359 May 27, 1999
Santus US2002/0077346 A1 Jun. 20,2002
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Application 13/688,659
Grounds of Rejection
Claims 15—18, 20—22, 24—28, 34, 35, 38-40, 43, and 44 stand rejected
under 35 U.S.C. §103(a) as being unpatentable over Karlsson.
Claims 29, 32, 33, 36, 37, 41, 42, and 45 stand rejected under 35
U.S.C. § 103(a) as being unpatentable over Karlsson in view of Santus.
FINDINGS OF FACT
The Examiner’s findings of fact are set forth in the Final Action at
pages 2—21. The following facts are highlighted.
1. Karlsson discloses that a glucocorticoid may be formulated with a
thickening agent. Karson 8. Karlsson further discloses:
The thickening agent may be present at about 0.1 to 3.0% w/w of
the formulation. Preferably microcrystalline cellulose and sodium
carboxymethyl cellulose (CMC) are present at about 0.5 to 2.5%,
xanthan gum at about 0.3 to 3%, carbomer at about 0.1 to 2%, guar
gum at about 0.3 to 2% and hydroxypropyl methyl cellulose at
about 0.5 to 3.0%, w/w of the formulation.
Id. at p. 9—10. Karlsson teaches that thickening agents assist in forming a
stable suspension with a minimal tendency to agglomerate. Id at p. 9.
2. Karlsson discloses that ciclesonide is a known, anti-inflammatory
glucocorticosteriod. Id. at p. 4.
PRINCIPLES OF LAW
In rendering our decision on patentability, we apply the
preponderance of the evidence standard. See, e.g., Ethicon, Inc. v. Quigg,
849 F.2d 1422, 1427 (Fed. Cir. 1988) (explaining the general evidentiary
standard for proceedings before the Office).
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Application 13/688,659
“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).
The burden of demonstrating unexpected results rests on the party
asserting them, and “it is not enough to show that results are obtained which
differ from those obtained in the prior art; that difference must be shown to
be an unexpected difference.” In re Klosak, 455 F.2d 1077, 1080 (CCPA
1972). “[UJnexpected results must be established by factual evidence. Mere
argument or conclusory statements in the specification does not suffice.” In
re DeBlauwe, 736 F.2d 699, 705 (Fed. Cir. 1984). “[W]hen unexpected
results are used as evidence of nonobviousness, the results must be shown to
be unexpected compared with the closest prior art.” In re Baxter-Travenol
Labs., 952 F.2d 388, 392 (Fed. Cir. 1991).
Obviousness Rejection over Karlsson
Appellants do not argue individual claims separately in the Brief. We
select claim 15 as representative claim. The Examiner finds that Karlsson
teaches each element claimed, however, also indicates that “Karlsson et al.
does not specifically exemplify an aqueous dispersion of powdered
ciclesonide, crystalline cellulose carmellose sodium and hydroxypropyl-
methyl cellulose. Karlsson et al. fails to teach the preferred percent weights
of the ciclesonide.” Ans. 5. The Examiner concludes, however, that
It would have been obvious to one of ordinary skill in the art at the
time the invention was made to use the teachings of Karlsson et al. to
exemplify an aqueous dispersion of powdered ciclesonide, crystalline
cellulose carmellose sodium and hydroxypropylmethyl cellulose
because Karlsson et al. teaches ciclesonide as a glucocortico-steroid
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Application 13/688,659
for use in their formulations and teaches crystalline cellulose
carmellose sodium and hydroxypropyl-methylcellulose as preferred
thickening agents for use in the formulation to minimize the tendency
for an agglomerate or sediment to form. Thus, an ordinary skilled
artisan would have been motivated to exemplify such a composition,
because of the expectation of achieving a formulation that effectively
treats an allergic and/or inflammatory condition of the nose or lungs
that does not agglomerate or sediment.
Id. at 4—5.
Appellants contend that
In view of Karlsson’s teaching that “[a]ll components, other than the
glucocorticosteroid, can be produced by sterile filtration of their
aqueous solutions”, a person of ordinary skill in the art would
recognize that only thickening agents which form a solution when
added to water (such as the preferred water soluble thickening agents
PEG and PVP) can be used in Karlsson’s formulation, while water-
insoluble or practically water-insoluble components such as
microcrystalline cellulose (MCC) would not be a suitable thickener to
use in Karlsson’s formulation, despite its inclusion in Karlsson’s list
of suitable thickeners on page 9.
App. Br. 11-12. Appellants argue that “Karlsson provides no teaching or
motivation for using a water insoluble or practically water insoluble
ingredient such as microcrystalline cellulose in its formulation,” as claimed.
App. Br. 12. In particular, Appellants argue that,
Karlsson does not use any practically water-insoluble or water-
insoluble Tdrugl ingredients, let alone MCC [microcrystalline
cellulose], in the formulations prepared in Examples 4 and 5 - wherein
“all of the components, other than the budesonide” either “were
produced” or “can be produced by sterile filtration of their aqueous
solutions.” Indeed, none of Karlsson’s example formulations include
any of the optional “thickening agents” outlined at page 9.
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App. Br. 12. Appellants further argue that, “the presently claimed subject
matter has demonstrated unexpectedly superior results over the cited
reference.” Id. 13.
ANALYSIS
We agree with the Examiner’s fact finding, statement of the rejection
and responses to Appellants’ arguments as set forth in the Answer. We
conclude that the Examiner has provided evidence to support a prima facie
case of obviousness. We provide the following additional comment to the
Examiner’s determinations set forth in the Final Rejection and Answer.
With respect to the Examiner’s prima facie case of obviousness,
Karlsson discloses glucocorticosteriods such as ciclesonide, formulated in a
preferred embodiment with overlapping ranges of crystalline cellulose
carmellose sodium or hydroxypropyl methyl cellulose with those claimed.
In cases involving overlapping ranges, we and our predecessor court
have consistently held that even a slight overlap in range establishes a
prima facie case of obviousness ....
Selecting a narrow range from within a somewhat broader range
disclosed in a prior art reference is no less obvious than identifying a
range that simply overlaps a disclosed range. In fact, when, as here,
the claimed ranges are completely encompassed by the prior art, the
conclusion is even more compelling than in cases of mere overlap.
The normal desire of scientists or artisans to improve upon what is
already generally known provides the motivation to determine where
in a disclosed set of percentage ranges is the optimum combination of
percentages.
In re Peterson, 315 F.3d 1325, 1329-1330 (Fed. Cir. 2003).
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As to Appellants’ argument that Karlsson does not use any practically
water-insoluble or water-insoluble thickening agent ingredients, such as a
microcrystalline cellulose thickening agent, the Examiner responded that
Isogai1 (of record) confirms that the microcrystalline cellulose disclosed in
Karlsson is capable of being dissolved in an aqueous sodium hydroxide
solution (abstract and pages 311—13), and an aqueous solution, as claimed.
Ans. 11. Appellants have not rebutted the Examiner’s evidence that
microcrystalline cellulose thickening agent disclosed in Karlsson (page 9,1.
31) is capable of being dissolved in an aqueous solution, as claimed.
We are also not persuaded that Appellants’ evidence of unexpected
results establishes the non-obviousness of the claimed subject matter.
Appellants direct our attention to the data presented in Table 1 of the
Specification at page 9. App. Br. 14. Appellants’comparative data
(compositions 6, 7) include two ciclesonide formulations including
crystalline cellulose carmellose sodium with either Polysorbate 80 or
Sorbitan trioleate. Spec. 8. However, Appellants have failed to compare the
claimed formulation with the closest prior art, e.g., the preferred formulation
on page 9 of Karlsson, which comprises microcrystalline cellulose and
sodium carboxymethyl cellulose (CMC)2 wherein the MCC is present at
about 0.5 to 2.5%, and hydroxypropyl methyl cellulose at about 0.5 to 3.0%,
w/w of the formulation. Appellants’ data does not show that changes in the
1 Isogai, “Dissolution of cellulose in aqueous NaOH solutions, ” 5
CELLUSOSE 309-319 (1998).
2 During the oral hearing on February 1, 2018, Appellants’ representative
stipulated that the combination of microcrystalline cellulose and sodium
carboxymethyl cellulose (CMC) form cellulose carmellose sodium.
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Application 13/688,659
amount of either the crystalline cellulose carmellose sodium or
hydroxypropyl methyl cellulose that differ from the claimed ranges, but are
within the ranges in Karlsson, provide unexpected results.
The obviousness rejection is affirmed.
Obviousness Rejection over Karlsson and Santus
Appellants do not argue individual claims separately in the Brief. We
select claim 29, which is dependent from claim 15, as a representative claim.
Appellants rely on their same arguments as set forth for the first
obviousness rejection to address this rejection. App. Br. 2. We remain
unpersuaded by these arguments.
In addition, Appellants argue that
A person of ordinary skill in the art would not modify Karlsson with
the water soluble formulation disclosed in Santus because Karlsson’s
pharmaceutical formulation includes a glucocorticosteriod, a water
insoluble active. Thus, a person of ordinary skill in the art would not
be motivated to modify the water insoluble suspension of Karlsson
with the water soluble solution taught by Santus to arrive at the
present claims particularly because problems arising with suspensions,
i.e. agglomeration or formation of sediments, simply does not occur
with solution formulations.
Id. at 28. We agree with the Examiner that
Karlsson et al. teaches a sterile pharmaceutical formulation
comprising a glucocorticosteroid and one or more pharmaceutically
acceptable additives, diluents or carriers, and examples of such
additives include surfactants, pH regulating agents, chelating agents,
agents rendering the suspension isotonic and thickening agents (page
8 lines 8-11). Karlsson et al. further teaches that agents which make
the suspension isotonic may be added which include dextrose,
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Application 13/688,659
glycerol, mannitol, sodium chloride, potassium chloride and sodium
bromide (page 9 liens [sic] 16-17).
Santus et at. also teaches therapeutic compositions for
intranasal administration (see abstract). Thus Santus and Karlsson are
clearly related since they both relate to pharmaceutical compositions
for intranasal administration for the treatment of inflammatory
conditions. Santus et al. teaches that suitable vehicles for aqueous
solutions include isotoning agents commonly used in pharmaceutics
such as sodium chloride and glucose, see [0019].
Ans. 19. Thus, we further agree with the Examiner that
it would have been obvious to one of ordinary skill in the art to use
glucose, as taught by Santus et al., as the isotonic agent of Karlsson et
al. because Santus et al. teach sodium chloride and glucose as
interchangeable isotonic agents, and Karlsson et al. teach sodium
chloride as an isotonic agent, thus, one would have been motivated to
substitute glucose for sodium chloride or add glucose with the sodium
chloride with a reasonable expectation of achieving equivalent or
better isotonic effects. Thus even though Karlsson et al. does not
teach glucose as an isotonic agent, Santus et al. teaches that glucose is
commonly used in pharmaceutical formulation which motivates one to
use glucose in the formulation of Karlsson. Moreover, it would have
been obvious to one of ordinary skill in the art at the time the instant
invention was made to incorporate the ascorbic acid of Santus et al.
into the composition of Karlsson et al. because of the expectation of
promoting absorption of the active agent. In addition, it would have
been obvious to one of ordinary skill in the art at the time the
invention was made to add the benzalkonium chloride as taught in
Santus et al. to the composition of Karlsson et al. because of the
expectation of preserving the composition and hence, increasing its
shelf life.
Id. at 20.
Rejection 2 is affirmed for the reasons of record.
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CONCLUSION OF LAW
The cited references support the Examiner’s obviousness rejections,
which are affirmed for the reasons of record. All pending, rejected claims
fall.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a). See 37 C.F.R.
§ 1.136(a)(l)(iv).
AFFIRMED
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