Ex Parte Chaudry

Patent Trial and Appeal Board

May 28, 2013

10414682 (P.T.A.B. May. 28, 2013)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte IMTIAZ CHAUDRY
__________

Appeal 2012-002355
Application 10/414,682
Technology Center 1600
__________

Before MELANIE L. McCOLLUM, JEFFREY N. FREDMAN, and
SHERIDAN K. SNEDDEN, Administrative Patent Judges.

FREDMAN, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal
1
under 35 U.S.C. § 134 involving claims to a nasal
pharmaceutical formulation of fluticasone. The Examiner rejected the
claims as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We affirm.

1
Appellant identifies the Real Party in Interest as Dey, L.P. (App.
Br. 3).
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2
Statement of the Case
Background
The Specification teaches “a nasal pharmaceutical formulation
comprising a drug substance having a specific particle size distribution
profile which provides increased bioavailability, increased efficacy or
prolonged therapeutic effect of the drug substance” (Spec. 2).
The Claims
Claims 1, 4, 6-9, 11-16, 28, 31, 33-36, 38, 50-56, 58, and 68-71 are on
appeal. Claim 1 is representative and reads as follows:
1. A nasal pharmaceutical formulation comprising an
aqueous suspension of a therapeutically effective amount of
fluticasone, wherein the aqueous suspension comprises
0.04% to 0.06% by weight of suspended solid fluticasone
particles having the following particle size distribution
profile:
about 10% of the fluticasone particles have a particle
size of less than 0.4 microns;
about 25% of the fluticasone particles have a particle
size of less than 0.75 microns;
about 50% of the fluticasone particles have a particle
size of less than 1.5 microns;
about 75% of the fluticasone particles have a particle
size of less than 3.0 microns; and
about 90% of the fluticasone particles have a particle
size of less than 5.3 microns;
wherein the fluticasone is suitable for administration
to an individual via intranasally.

The issue
The Examiner rejected claims 1, 4, 6-9, 11-16, 28, 31, 33-36, 38, 50-
56, 58, and 68-71 under 35 U.S.C. § 103(a) as obvious over Physician’s
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Desk Reference (PDR®),
2
Drug Information Handbook,
3
Bernini,
4
and
Osbakken
5
(Ans. 5-10).
The Examiner finds that
FLONASE® is a commercially available nasal spray
sold in a metering, atomizing, spray pump containing therein
an aqueous suspension of suspended microfine fluticasone
propionate (16 g bottle delivering 120 individual 50
microgram doses per actuation; i.e. 0.0375% w/w
fluticasone propionate), microcrystalline cellulose,
carboxymethylcellulose sodium dextrose, 0.02% w/w
benzalkonium chloride, polysorbate 80, 0.25% w/w
phenylethyl alcohol wherein the aqueous suspension has a
pH between 5 and 7

(Ans. 5). The Examiner finds that the “DIH demonstrates that FLONASE®
was a commercially available product at least in 1999” (id. at 6).
The Examiner finds that Bernini teaches “preparation of suspensions
of drug particles for inhalation deliver either nasal or pulmonary, providing
optimized particle size and distribution” (id.). The Examiner finds that
Bernini teaches compounds “used in the form of micronized powder, in the
form of particles having a MMAD of less than preferably 5 µm” (id.).
The Examiner finds that Osbakken teaches that “aerosolized anti-
infective particles are surprisingly effective when they have a mass median

2
Physician’s Desk Reference (PDR), Flonase entry, accessed on
December 1, 2007 at
www.thomsonhc.com/pdrel/librarian/ND_PR/Pdr/SBK/l//PFPUI/0
SlHrZu2aVaNqC/DDAK (We will hereinafter refer to this
reference as “PDR”).
3
Lacey et al., Drug Information Handbook 447 (1999-2000).
4
Bernini et al., US 6,464,958 B1, issued Oct. 15, 2002.
5
Osbakken et al., US 2002/0061281 A1, published May 23, 2002.
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aerodynamic diameter (MMAD) of about 1.0 to 5.0 microns” (Ans. 7). The
Examiner finds that Osbakken teaches that “[a]erosolization/atomization of
the formulations for nasal inhalation by a patient will result in liquid aerosol
cloud particles having a MMAD of preferably between about 0.5 microns
and 10 microns” (id.). The Examiner finds that Osbakken teaches the use of
fluticasone (id.).
The Examiner finds it obvious, based on the prior art “to modify the
particle size distribution of a composition comprising fluticasone because it
is well known in the art that the particle size distribution of an aerosolized
drug composition is very important to the therapeutic efficacy of the drug
when delivered by inhalation” (id.). The Examiner finds “the physical
characteristics (e.g. size and shape) of particulate compositions are clearly
result specific parameters that a person of ordinary skill in the art would
routinely optimize” (id. at 8).
The issues with respect to this rejection are:
(i) Does the evidence of record support the Examiner’s conclusion
that the cited prior art renders claim 1 obvious?
(ii) If so, has Appellant presented evidence of secondary
considerations, that when weighed with the evidence of obviousness, is
sufficient to support a conclusion of non-obviousness?
Findings of Fact
The following findings of fact (“FF”) are supported by a
preponderance of the evidence of record.
1. Flonase (PDR) teaches that:
FLONASE Nasal Spray, 50 mcg is an aqueous suspension
of microfine fluticasone propionate for topical
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administration to the nasal mucosa by means of a metering,
atomizing spray pump. FLONASE Nasal Spray also
contains microcrystalline cellulose and
carboxymethylcellulose sodium, dextrose, 0.02% w/w
benzalkonium chloride, polysorbate 80, and 0.25% w/w
phenylethyl alcohol, and has a pH between 5 and 7.

(Flonase 1.)
2. The Drug Information Handbook teaches fluticasone,
demonstrating the drug was known in 1999 (see DIH 445).
3. Bernini teaches that “[o]ne of most critical parameters
determining the proportion of inhalable drug which will reach the lower
respiratory tract of a patient is the size of the particles emerging from the
device” (Bernini, col. 1, ll. 30-33).
4. Bernini teaches that “[o]ther important characteristics for a
correct administration and therefore for the therapeutic efficacy, are the size
distribution and the homogeneous dispersion of the particles in the
suspension” (Bernini, col. 1, ll. 39-42).
5. Bernini teaches that “in case of steroids, it is possible to tighten
the distribution particle curve in such a way as that the mean diameter of at
least 90% of the particles is lower than or equal to 5 µm by keeping the
operating pressures between 500 and 1000 bar” (Bernini, col. 2, ll. 44-48).
6. Table 2 of Bernini is partially reproduced below:

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Table 2 shows particle sizes for the inhaled steroid BDP where 10% was
0.76 µm, 50% was 3.01 µm, and 90% was 9.42 µm.
7. Osbakken teaches that “the sinus passages must be open to
allow drainage and the circulation of air through the nasal passage. When
one or more of these processes or factors are amiss, causing obstruction of
the sinus passage, an infection called sinusitis develops” (Osbakken 1 ¶
0004).
8. Osbakken teaches “using a nebulizer to treat sinusitis patients.
. . . Kondo et al. suggests that the preferred aerosol particle size is about 2-4
µm in diameter for deposition of a higher level of antibiotic in the maxillary
sinus” (Osbakken 3 ¶¶ 0027, 0029).
9. Osbakken teaches “that aerosolized anti-infective particles are
surprisingly effective therapeutically when they have a mass median
aerodynamic diameter (MMAD) of about 1.0 to 5.0 microns for deposition
in the sinuses in a preferred size range” (Osbakken 6 ¶ 0081).
10. Osbakken teaches that “[e]xamples of steroidal anti-
inflammatories include, but are not limited to . . . fluticasone” (Osbakken 10
¶ 0139).
11. Osbakken teaches that after “determining the medications to be
used in the formulation, each ingredient is weighed/measured out
individually, added together, mixed with diluent, for example, sterile water,
and filtered with a coarse filter and then a fine filter (5 micron, 2 micron, 1
micron, 0.45 micron, or 0.22 micron)” (Osbakken 8 ¶ 0104).
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12. Osbakken teaches nasal delivery of an aqueous suspension,
teaching “the topical delivery of medications to the nasal cavity and sinuses
by aerosolizing aqueous solutions or suspensions” (Osbakken 6 ¶ 0081).
13. Figure 3 of Chemimage
6
is reproduced below:

Figure 3 shows the particle size of fluticasone in Flonase and in a generic
equivalent.
Principles of Law
“In proceedings before the Patent and Trademark Office, the
Examiner bears the burden of establishing a prima facie case of obviousness
based upon the prior art.” In re Fritch, 972 F.2d 1260, 1265 (Fed. Cir. 1992).

6
Chemimage, Comparison of Drug Particle Sizing of Innovator
and Generic Nasal Spray Formulation Based on Raman Chemical
Imaging, www.chemimage.com (2009).
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“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’l Co. v. Teleflex lnc., 550 U.S. 398, 416 (2007). “If a person of
ordinary skill can implement a predictable variation, § 103 likely bars its
patentability.” Id. at 417.
Analysis
Prima Facie Obviousness
Osbakken teaches treatment of fungus induced sinusitis in a mammal
(FF 8-9) comprising the use of the anti-inflammatory fluticasone (FF 10).
While Osbakken does not teach the precise particle size distribution profile
of claim 1, Osbakken teaches “that aerosolized anti-infective particles are
surprisingly effective therapeutically when they have a mass median
aerodynamic diameter (MMAD) of about 1.0 to 5.0 microns for deposition
in the sinuses in a preferred size range” (Osbakken 6 ¶ 0081; FF 9).
Osbakken’s range of particle sizes, with a low value of 1.0 microns,
reasonably overlaps the range recited in claim 1. See In re Peterson, 315
F.3d 1325, 1329 (Fed. Cir. 2003) (“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.”)
The particle size distribution of Flonase, as disclosed by Chemimage,
is d10 1, d50 4.7, d90 13.5 (FF 13). Bernini teaches that particle size
distribution is an optimizable variable, where Bernini teaches that “[o]ne of
most critical parameters determining the proportion of inhalable drug which
will reach the lower respiratory tract of a patient is the size of the particles
emerging from the device” (Bernini, col. 1, ll. 30-33; FF 3).
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We conclude that the person of ordinary skill and creativity would
have predictably optimized the distribution of fluticasone particles for the
treatment of sinusitis since the prior art references suggest that particle size
distributions were known as a results effective variable, critical for
determining the deposition of the particles into the sinus (FF 3, 6, 8, 9, 13).
“[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) (citing In re
Dreyfus, 73 F.2d 931 (CCPA 1934); In re Waite, 168 F.2d 104 (CCPA
1948)).
Appellant contends that
one skilled in the art would have no rational basis for
modifying Flonase to have the particular particle size
distribution recited in each of the currently pending
independent claims. Such a modification would require a
substantial alteration of the Flonase particle size
distribution, particularly considering the lack of any
teaching in the art to make such a modification

(App. Br. 13).
We are not persuaded. Osbakken teaches “that aerosolized anti-
infective particles are surprisingly effective therapeutically when they have a
mass median aerodynamic diameter (MMAD) of about 1.0 to 5.0 microns
for deposition in the sinuses in a preferred size range” (Osbakken 6 ¶ 0081;
FF 9). The discovery of an optimum value of a results-effective variable in a
known process is normally obvious. In re Antonie, 559 F.2d 618, 620
(CCPA 1977). As discussed above, particle size distributions for sinusitis
drugs were known, results-effective variables (FF 3, 6, 8, 9, 13) and
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Osbakken suggests particle sizes including a 1.0 micron particle size which
overlaps with the distribution claimed by Appellant. See In re Peterson, 315
F.3d at 1329 (“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.)
Unexpected Results
Appellant contends that “[c]omparison of the Dey FP Low Dose
Group with the Flonase Low Dose Group shows that the currently claimed
invention provides a notable and surprising improvement from the
symptoms of SAR despite both groups receiving the same amount of active”
(App. Br. 14).
Appellant “submits that one skilled in the art (and one suffering from
the symptoms of seasonal allergic rhinitis) would recognize the
aforementioned percentages of TNSS improvement as not merely a minor
difference of degree” (id. at 15). Table 1 in Appellant’s brief shows a range
of improvements from 9% to 38% between the claimed particle distribution
and the Flonase low dose group, based upon data in the figures (see id.).
We are not persuaded. We note that the “Table 1” presented in both
the Appeal Brief and Reply Brief is not found in the Specification or
Drawings. Appellant does not indicate or explain where the data was
obtained for Table 1. It is unclear if this data was generated by Appellant’s
attorney from the Figures, generated using original data, or obtained in some
other fashion. This Table is therefore not persuasive as evidence to
overcome the Examiner’s prima facie case.
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We have reviewed figures 1-4 and Example 6 of the Specification and
do not find that the results are unexpected. Example 6 directly rebuts the
unexpected results argument of Appellant, since Example 6 states that
“[t]here was no statistically significant differences between Dey-FP and
FLONASE High and Low Dose groups for any efficacy endpoint analysis
(relief of signs and symptoms of SAR)” (Spec. 28).
Figures 1 and 2 are reproduced below:

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FIGs. 1 and 2 show the change from baseline in AM and PM reflective
TNSS over time in the ITT or PP populations over a 14 day study period. A
careful review of Figure 1 supports the position of the Examiner, which is
that the Dey fluticasone low values were substantially the same as those of
Flonase low values, with minimal difference over the 14 days. Figure 2 of
the Specification shows a virtual overlap between the two groups on days 5,
9, and 10, and very close numbers on day 14. This is consistent with the
evidence of Example 6 of the Specification that there is no significant or
unexpected differences. See In re Klosak, 455 F.2d 1077, 1080 (CCPA
1972) (“[i]t 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”).
There is no evidence of record which explains why the data in “Table
1” or the data in the Specification is unexpected. At best, there is attorney
argument in the Reply Brief that “[s]urprisingly, the recited PSD has been
shown to provide individuals with an increased reduction in the total
symptoms of rhinitis as compared to the results realized by individuals
receiving the same amount of active from Flonase” (Reply Br. 3). However,
unexpected results must be established by factual evidence, and attorney
statements are insufficient to establish unexpected results. See In re Geisler,
116 F.3d 1465, 1470-71 (Fed. Cir. 1997). We here emphasize that Appellant
has not identified any location in the Specification where Appellant
characterizes these results as unexpected. It is only the Appellant’s attorney
in the Brief and Reply Brief who describes these results as unexpected.
Attorney’s arguments in a brief cannot take the place of evidence. In re
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Pearson, 494 F.2d 1399, 1405 (CCPA 1974). See also In re De Blauwe, 736
F.2d 699, 705 (Fed. Cir. 1984) (Arguments and conclusions unsupported by
factual evidence carry no evidentiary weight.)
Conclusion of Law
(i) The evidence of record supports the Examiner’s conclusion that the
cited prior art renders Claim 1 obvious.
(ii) Appellant has not presented evidence of secondary considerations,
that when weighed with the evidence of obviousness, is sufficient to support
a conclusion of non-obviousness.
SUMMARY
In summary, we affirm the rejection of claim 1 under 35 U.S.C. §
103(a) as obvious over Physician’s Desk Reference (PDR®), Drug
Information Handbook, Bernini, and Osbakken. Pursuant to 37 C.F.R. §
41.37(c)(1), we also affirm the rejection of claims 4, 6-9, 11-16, 28, 31, 33-
36, 38, 50-56, 58, and 68-71 as these claims were not argued separately.

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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