Ex Parte MORTON et al

Patent Trial and Appeal Board

Sep 20, 2018

12967306 (P.T.A.B. Sep. 20, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
12/967,306 12/14/2010 David MORTON
22850 7590 09/24/2018
OBLON, MCCLELLAND, MAIER & NEUSTADT, L.L.P.
1940 DUKE STREET
ALEXANDRIA, VA 22314
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.
372030US68 1387
EXAMINER
HAGHIGHATIAN, MINA
ART UNIT PAPER NUMBER
1616
NOTIFICATION DATE DELIVERY MODE
09/24/2018 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):
patentdocket@oblon.com
OBLONPAT@OBLON.COM
tfarrell@oblon.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte DAVID MORTON, QI ZHOU,
and ROSSELLA MUSA
Appeal2017-002010
Application 12/967,306 1
Technology Center 1600
Before: FRANCISCO C. PRATS, JEFFREY N. FRED MAN, 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 to a capsule
for use with a dry powder inhaler. The Examiner rejected the claims on
Appeal under 35 U.S.C. § 112 as indefinite and under 35 U.S.C. § 103(a) as
obvious. We have jurisdiction pursuant to 35 U.S.C. § 6(b).
We AFFIRM.
1 According to Appellants, Chiesi Farmaceutici S.P.A. is the real party in
interest. App. Br. 2.
Appeal2017-002010
Application 12/967 ,306
STATEMENT OF THE CASE
The Specification discloses that cystic fibrosis ("CF") is associated
with "viscid mucus in the airways" which "allows bacterial colonization,
with consequent infection of the respiratory tract, contributing to ongoing
tissue damage." Spec. 1. The airway is first colonized by Haemophilus
influenza and Staphylococcus aureus followed by Pseudomonas aeruginosa
after which "the colonization becomes chronic in most CF patients, and
virtually impossible to be eradicated." Id. at 2.
"[ A ]ntibiotics belonging to the family of aminoglycosides, and in
particular tobramycin, are ... currently utilized via parenteral route" to
"oppose the CF progression by reducing pulmonary deterioration and
improving lung function." Id. "However, aminoglycosides penetrate
endobronchial secretions (sputum) poorly, necessitating large intravenous
doses to attain an efficacious concentration at the site of infection. These
high doses place the patient at risk for nephrotoxic and ototoxic effects." Id.
The Specification discloses that aqueous formulations of tobramycin are
currently marketed for use with nebulizers however, nebulizers have poor
patient compliance, are prone to bacterial contamination, and have low
efficacy. Id.
The Specification discloses that "[p ]owder formulations to be
administered by suitable devices, known as Dry Powder Inhalers (DPis) may
be considered a suitable alternative to tobramycin formulations for
nebulisation, as these systems could provide easier and more rapid drug
administration." Id. at 3. Development of an efficacious tobramycin dry
powder formulation requires solving problems "normally faced in
manufacturing said kind of formulations" including ensuring that it exhibits
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"suitable flowability, adequate chemical and physical stability in the device
before use, and give[ s] rise to a good respirable fraction as well as deliver an
accurate therapeutically active dose of the active ingredient." Id. In
addition, because "tobramycin is hygroscopic" and "humidity could also
affect flowability, particular attention should be paid in reducing the amount
of residual water as well as the water uptake after storage." Id. The
Specification asserts that the "tasks of making tobramycin formulation for
DPI appear not to be easily solved as currently no product has been
marketed yet." Id.
The Specification discloses "it is one object of the present invention to
provide novel dry powder formulations for pulmonary administration of an
antibiotic belonging to the family of aminoglycosides, which alleviate the
drawbacks discussed above." Id. at 4. This object has been achieved by:
the inventors' discovery that a dry powder formulation
for pulmonary administration comprising mechano-fused
microparticles containing particles of an antibiotic
belonging to the family of aminoglycosides in an amount
equal to or higher than 90% w/w and magnesium stearate
in an amount equal to or lower than 10% w/w, wherein
magnesium stearate coats the surface of the drug particles
by at least 50%, and optionally a physiologically
acceptable pharmacologically-inert carrier, are effective
for the treatment of bacterial endobronchial infections
associated with certain pulmonary diseases.
Id. at 4--5.
Claims 7, 8, 11, 12, 14, 15, and 28-34 are on appeal. Claim 11
below is illustrative, and reads as follows:
11. A capsule for use with a dry powder inhaler, which
contains a dry powder formulation for delivery of
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tobramycin to the lungs, said formulation comprising
mechano-fused microparticles,
wherein said mechano-fused microparticles consist
of:
(a) particles of tobramycin in an amount of 99 to
99.5 w/w; and
(b) magnesium stearate in an amount of 0.5 to 1 %
w/w,
wherein magnesium stearate coats at least 50% of
the surface of the particles of tobramycin,
wherein said microparticle have an amount of
residual water lower than 5% w/w, and
wherein said capsule contains 12 to 40 mg of said
tobramycin expressed as free base.
App. Br., Claim App.1-2.
The claims stand rejected as follows. 2
Claims 33 and 34 were rejected under 35 U.S.C. § 112 as indefinite.
Claims 7, 8, 11, 12, 14, 15, and 28-34 were rejected under 35 U.S.C.
§ 103 (a) as obvious over the combination of Staniforth, 3 Stein, 4 and
Challoner. 5
INDEFINITENESS
Claims 33 and 34 are dependent claims which recite that
administration of the claimed formulation from the capsule to the lungs of a
2 In the Examiner's Answer, the Examiner withdrew the pending rejection
of claims 33 and 34 under 35 U.S.C. § 112 for failure to comply with the
written description requirement. Ans. 2. This rejection is thus no longer a
part of this appeal.
3 Staniforth et al., US 2004/0071635 Al; published Apr. 15, 2004
("Staniforth").
4 Stein et al, Mechanofusion for High Peiformance Particles, Process
Engineering, Vol. 79, No. 4, El 1-EI5 (2002) ("Stein").
5 Challoner et al., US 2008/0214481 Al; published Sep. 4, 2008
("Chall oner").
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subject "results in rapid delivery of said tobramycin." App. Br., Claim App.
4. In finding these claims indefinite, the Examiner found that the term
"rapid" was a relative term and that the Specification "does not provide a
standard for ascertaining the requisite degree, and one of ordinary skill in the
art would not be reasonably apprised of the scope of the invention." Final
Act. 3. 6 We are not persuaded
We agree with the Examiner that the term "rapid" is a relative term.
However, relative terms are not necessarily indefinite. Interval Licensing
LLC v. AOL, Inc., 766 F.3d 1364, 1370 (Fed. Cir. 2014) ("Claim language
employing terms of degree has long been found definite where it provided
enough certainty to one of skill in the art when read in the context of the
invention."). Here, the Specification states that the dry powder inhalers,
which are used to administer the claimed capsules, "may be considered a
suitable alternative to tobramycin formulations for nebulisation, as these
systems could provide easier and more rapid drug administration." Spec. 3.
In the context of this disclosure, we agree with Appellants the skilled artisan
would have understood the term "rapid delivery" to require delivery "more
quickly than formulations administered by nebulization." Reply Br. 2.
Accordingly, we reverse the Examiner's rejection of claims 33 and 34 as
indefinite.
OBVIOUSNESS
Findings of Fact
1. Staniforth discloses:
The present invention provides a method of making a
composition for inhalation which includes the step of mixing
6 Office Action mailed January 15, 2016 ("Final Act.").
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particles of additive material having a diameter of not more
than 2 µm with active particles, wherein the additive material is
suitable for promoting the dispersal of particles upon
aerolisation of a dry powder in a dry powder inhaler.
Staniforth ,r 15.
2. Staniforth discloses:
Compositions for inhalation comprising the particles of additive
material according to the invention may demonstrate improved
dispersal of the active particles on actuation of the inhaler
and/or delayed release of the active substance after deposition
in the lungs. It is believed that those improved properties are
achieved because the additive particles are smaller than known
additive particles and can therefore more effectively surround
or coat the active particles.
Id. ,I 16.
3. Staniforth discloses:
The additive material is suitable for promoting the dispersal of
particles of active substance upon actuation of a dry powder
inhaler. Such additive materials, when included in a powder for
use in a dry powder inhaler, increase the fine particle fraction of
the active substance delivered upon actuation of the inhaler as
compared to a similar powder not comprising the additive
material.
Id. ,I 26.
4. Staniforth discloses: "Preferably, the additive material
comprises magnesium stearate." Id. ,r 32.
5. Staniforth discloses: "Preferably, the composition is a dry
powder and is suitable for use in a dry powder inhaler." Id. ,r 46.
6. Staniforth discloses: "Preferably, the active substance is a
biological macromolecule, for example, a polypeptide, a protein, or a DNA
fragment." Id. ,r 5 5.
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7. Challoner discloses: "The present invention relates to new and
improved methods for treatment of susceptible endobronchial infections in
patients with dry powder formulations of aminoglycoside antibiotics, such as
tobramycin." Challoner ,r 2.
8. Challoner discloses:
Id. ,I 16.
The present invention provides methods for the treatment
of endobronchial infections in a patient, comprising
administering to the endobronchial system of the patient a
dry powder aerosol composition comprising from 90 to
130 mg of an aminoglycoside antibiotic one to three times
a day for a first treatment period of 20 to 36 days.
9. Challoner discloses:
Id. ,I 68.
[T]he aerosol powder can include one or more excipients,
and/ or any other component that improves the
effectiveness of the aminoglycoside antibiotic .... Such
excipients may also serve to improve the dispersability of
the powder within a powder dispersion device in order to
provide more efficient and reproducible delivery of the
active agent and to improve the handling characteristics of
the active agent (e.g., flowability and consistency) to
facilitate manufacturing and powder filling.
10. Challoner discloses: "Also suitable for delivering the
aminoglycoside powders described herein are dry powder inhalers." Id.
11. Chall oner discloses a comparison between (a) systemic
concentrations of tobramycin resulting from solution administration by jet
nebulizer (TOBI®) and (b) systemic concentrations of tobramycin resulting
from administration using inhaled powder (TPI). See id. ,r,r 246, 309, 338,
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404, 408, and 410. Challoner concludes that "[ s ]ystemic exposures achieved
after administration of TOBI® Tobramycin Solution for Inhalation were
very similar to that seen after administration of 4x28 mg capsules of TIP
[sic, TPI], with an equivalent dose calculation of 115 mg of TIP [sic, TPI]."
Id.,I410.
12. Challoner discloses: "Mean serum concentration-time profiles
of tobramycin after administration of TPI and TOBI indicate that the drug is
rapidly absorbed: tmax was 1 hour in all treatments." Id. ,r 336, Table 7.
13. Challoner discloses: "Bronchodilator use may increase the
amount of the tobramycin that eventually reaches systemic circulation,
perhaps by an increase in the amount deposited in the lungs." Id. ,r 334.
14. Challoner discloses: "The powdered aminoglycoside antibiotic
formulations useful in the practice of the present invention typically contain
less than 15% by weight moisture, usually below about 11 % by weight, and
preferably below about 8% by weight." Id. f 62.
Analysis
Claim 11
In finding claim 11, the only independent claim on appeal, obvious,
the Examiner found that Staniforth disclosed particles of magnesium stearate
adhered to the surfaces of particles of active agent using a mechano-fusion
process. Final Act. 5. The Examiner found that the particles disclosed in
Staniforth included all of the elements of claim 11 except that Staniforth did
not disclose the use of tobramycin as the active, or its dosage. Final Act. 7.
To address these deficiencies, the Examiner relies on Challoner as disclosing
"the treatment of an endobronchial infection in a patient by administering to
the endobronchial system of the patient a dry powder aerosol composition
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comprising from 90 to 130 mg of an aminoglycoside antibiotic" wherein
"suitable aminoglycoside[s] include tobramycin." Id. at 7-8.
Based on the combined teachings of Staniforth, Challoner, and Stein, 7
the Examiner concluded that it would have been obvious to have used
tobramycin, as taught by Challoner, in Staniforth's mechano-fusion particles
"because Staniforth et al teach preparing a microparticles consisting of an
active agent suitable for inhalation such as antibiotic coated with magnesium
stearate by mechanofusion" and "Challoner et al teach that tobramycin as [a]
dry powder administration via inhalation is suitable for treating bronchial
infections and discloses its suitable doses." Id. at 8-9. Further, Staniforth
discloses that its microparticles "demonstrate improved dispersal of the
active particles on actuation of the inhaler and/or delayed release of the
active substance after deposition in the lungs" and that these "improved
properties are achieved because the additive particles are smaller than
known additive particles and can therefore more effectively surround or coat
the active particles." Ans. 4. The Examiner concluded that this would have
provided "reason/motivation to one of ordinary skill in the art to make and
use microparticles according to [Staniforth's] guidance." Id.
We agree with the Examiner that the combination of Staniforth,
Challoner, and Stein would have rendered the claimed capsules obvious.
We address Appellants' arguments below.
Relying on the testimony of Dr. Francesca Buttini, Appellants contend
that the skilled artisan would have understood that the particles disclosed in
7 The Examiner relied upon Stein as teaching the application of mechano-
fusion to pharmaceuticals and a process time for mechano-fusion in the
range of between 5 and 120 minutes. Final Act. 7.
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Staniforth were useful for systemic delivery of the active material. App. Br.
16-22 ( citing Buttini Deel. II). 8 Appellants further contend the skilled
artisan "would have understood that tobramycin should not be delivered
systemically but, instead, should be delivered locally." Id. at 22-24 ( citing
Buttini Deel. II). Appellants thus argue that "because one of skill in the art
would understand that: (1) the particles disclosed in Staniforth would be
effective for systemic delivery of the active material; and (2) tobramycin
should not be delivered systemically but, instead should be delivered locally,
a skilled artisan would not have looked to Staniforth when attempting to
develop a formulation for the administration of tobramycin." Id. at 24. We
are not persuaded.
Challoner teaches the administration of tobramycin in an inhalable dry
powder aerosol composition to treat endobronchial infections in patients.
FF7, FF8, FFlO. Staniforth teaches a process of making a composition for
inhalation by "mixing particles of additive material having a diameter of not
more than 2 µm with active particles." FFl. The additive material is
preferably magnesium stearate. FF4. Staniforth's process results in a dry
powder aerosol composition that "demonstrate[s] improved dispersal of the
active particles." FF2, FF3, and FF5. Accordingly, we agree with the
Examiner that it would have been obvious to use Staniforth's process for
making dry powder aerosol compositions to obtain improved dispersion of
the tobramycin dry powder aerosol composition disclosed in Challoner.
Ans. 4.
8 Declaration of Dr. Francesca Buttini, dated May 23, 2015 ("Buttini Deel.
II").
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We acknowledge the evidence presented by Appellants that
tobramycin should not be administered systemically. See, e.g., Buttini Deel.
II, ,r 15 and references cited therein. However, we are not persuaded that
this would have discouraged the skilled artisan from using Staniforth' s
process to obtain a tobramycin dry powder aerosol with improved
dispersion. In this regard, we note that both Challoner and Staniforth
disclose dry powder aerosol compositions (see FFl, FF3, FF5, FF7, FF8,
and FFlO) and that Challoner expressly contemplates the use of excipients
and other components to "improve the dispersability of the powder." FF9.
Moreover, Challoner expressly contemplates that at least some portion
of its tobramycin dry aerosol powder will be delivered systemically. FF 11-
13. Thus, while Appellants' arguments and the Buttini Declarations provide
some evidence that the skilled artisan would not combine the teachings of
Staniforth and Challoner, when these findings are weighed against the
specific teachings of Challoner and Staniforth, we find that the balance of
evidence supports the Examiner's finding that the claimed capsule would
have been obvious.
Appellants argue that "being an antibiotic, to achieve the minimum
inhibitory concentrations (MIC), tobramycin should act very fast and its
delivery at the infection site should not be delayed." App. Br. 26. This
statement, however, is not supported by evidence. See, Johnston v. IVAC
Corp., 885 F.2d 1574, 1581 (Fed. Cir. 1989) ("Attorneys' argument is no
substitute for evidence."); In re Pearson, 494 F.2d 1399, 1405 (CCPA
1974). Accordingly, we are not persuaded by Appellants' argument that "a
skilled artisan would have thought the use of magnesium stearate to be
incompatible with achieving a fast delivery of tobramycin." App. Br. 26.
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Appellants argue that tobramycin is considered a thermolabile active
substance and thus a skilled artisan would have "had concerns in regard to
processing tobramycin with a mechano-fusion apparatus" that uses heat to
soften and break the particles. App. Br. 15. However, Staniforth discloses
that its mechano-fuision process can be used with proteins and polypeptides.
FF6. The Examiner finds, and Appellants do not dispute, that proteins and
polypeptides are thermolabile. Ans. 6. Accordingly, we are not persuaded
that the skilled artisan would have been discouraged from using a mechano-
fusion process with tobramycin because it is thermolabile.
Appellants argue that when tobramycin dry powders prepared by the
mechano-fusion process described in Appellants' application were compared
with tobramycin prepared according to Challoner, the mechano-fusion dry
powder "performed better than the powder according to Challoner due to the
better flowability of these powders." App. Br. 34; see also generally, App.
Br. 27-36; Buttini Deel. I. ,r,r 11-17. 9 Dr. Buttini testifies that "[t]he
improvement in the flow properties of the mechano-fused micropowders
according to the above-identified application ... as compared to the powder
prepared by spray drying according to Challoner et al., could not have been
predicted prior to the time the invention described in the above-identified
application was made, even in view of the combined teachings of Staniforth
et al., Stein et al., and Chall oner et al." Buttini Deel. I, ,r 17. We are not
persuaded.
Staniforth teaches that particles produced by its mechano-fusion
process "demonstrate improved dispersal" and that this property is
9 Declaration of Dr. Francesca Buttini dated November 14, 2014 ("Buttini
Deel. I").
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attributable to the additive particles. FF2, FF3. Based on these teachings
the skilled artisan would reasonably have expected that applying Staniforth's
teachings to Challoner's tobramycin would improve the dispersal
characteristics - i.e. the flow - of the tobramycin. We acknowledge Dr.
Buttini's opinion that the improved flow would have been unexpected
(Buttini Deel. I, ,r 17), however, neither Appellants nor Dr. Buttini provide
persuasive evidence or argument explaining why the skilled artisan would
not have been expected that the use of mechano-fusion would improve flow
characteristics. See In re Am. Acad, of Sci. Tech Ctr., 367 F.3d 1359, 1368
(Fed. Cir. 2004) ("[T]he Board is entitled to weigh the declarations and
conclude that the lack of factual corroborations warrants discounting the
opinions expressed in the declarations."). Nor do Appellants present
persuasive evidence or argument that the magnitude of improvement in flow
characteristics is beyond what would have been expected in view of
Staniforth' s teachings. We are thus not persuaded that unexpected results
demonstrate the non-obviousness of the claimed capsules. Accordingly, we
affirm the Examiner rejection of claim 11 as obvious over the combination
of Staniforth, Challoner, and Stein.
Claim 7
Claim 7 depends from claim 11, and further requires that the
microparticles have an amount of residual water of 4.5 to 4.8% w/w.
Appellants argue that "Challoner does not remotely disclose or suggest a
capsule including microparticles including tobramycin and magnesium
stearate and having an amount of residual water in the particular range of 4.5
to 4.8% w/w." App. Br. 37. We are not persuaded because Challoner
discloses a range of moisture content that encompasses the claimed range.
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FF14. This creates a prima facie case of obviousness and shifts the burden
to the Appellants to demonstrate nonobviousness. In re Peterson, 315 F.3d
1325, 1329--30 (Fed. Cir. 2003). As Appellants have not provided
persuasive evidence demonstrating the non-obviousness of the claimed
water content, we affirm the Examiner's rejection of claim 7.
Claim 8
Claim 8 depends from claim 11, and further requires that the
formulation includes a physiologically acceptable pharmacologically-inert
carrier. Appellants argue that "there is nothing in Staniforth indicating
whether or which carriers could be incorporated into microparticles
including tobramycin and magnesium stearate" and that the Examiner
"merely identifies disclosure of a carrier but does not address the
applicability of such carrier to a formulation that is beyond the scope of
Staniforth (i.e., a formulation including tobramycin)." App. Br. 38-39
( emphasis omitted). We are not persuaded.
As the Examiner points out, claim 8 does not limit the potential
carriers. Ans. 12. As such, any carrier would meet the additional limitation
recited in claim 8. Staniforth and Challoner both disclose suitable
carriers/excipients and both list lactose. Staniforth ,r 46; Challoner ,r 70. As
both Staniforth and Challoner contemplate the use of a carrier, we agree with
the Examiner that it would have been obvious to use one. Accordingly, we
affirm the Examiner's rejection of claim 8.
Claims 28 and 29
Claim 2 8 depends from claim 11, and further requires the presence of
15 to 30 mg of the tobramycin expressed as a free base. Claim 29 depends
from claim 11, and further requires the presence of 15 mg of the tobramycin
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expressed as a free base. Appellants argue that "the formulation in
Challoner does not include magnesium stearate as required in the
microparticles of claims 28 and 29" and that the Examiner "merely identifies
disclosure of dosages of tobramycin but does not address the applicability of
such dosages to a formulation that is beyond the scope of Challoner (i.e., a
formulation including magnesium stearate)." App. Br. 40. We are not
persuaded.
Challoner exemplifies dry powder capsules including 14, 27, and 28
mg of tobramycin as a free base. Challoner ,r,r 64, 92, and 98-103 (see also,
Final Act. 8 ( discussing same)). These amounts overlap with or are very
close to the amount recited in claims 28 and 29. In re Peterson, 315 F.3d
1325, 1329-30 (Fed. Cir. 2003); Titanium Metals Corp. of America v.
Banner, 778 F.2d 775, 783 (Fed. Cir. 1985). Appellants have not provided
persuasive evidence or argument explaining why these dosages - all of
which relate to dry powder formulations - would not be applicable to
Staniforth's dry powder formulation. Accordingly, we affirm the
Examiner's rejection of claims 28 and 29.
Claims 30-32
Claim 3 0 depends from claim 11, and further requires that the capsule
is a 3 HPMC capsule or a gelatine capsule. Claim 31 depends from claim
11, and further requires that the capsule is a 3 HPMC capsule. Claim 32
depends from claim 11, and further requires that the capsule is a gelatine
capsule. Appellants argue that "[t]he examiner merely identifies disclosure
of capsules used to hold a tobramycin formulation but does not address the
applicability of such capsules to a formulation that is beyond the scope of
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Challoner (i.e., a formulation including magnesium stearate)." App. Br. 41
( emphasis omitted). We are not persuaded.
Challoner discloses using HPMC capsules and gelatin in connection
with its dry powder tobramycin formulation. See, e.g., Challoner ,r,r 83, 152.
The Examiner also finds, and Appellants do not dispute, that it was "well
known in the art to make capsules of HPMC or gelatin." Ans. 13. We thus
agree with the Examiner that it would have been obvious to use HPMC or
gelatin for capsules in Staniforth's process. In this regard, we note that
Appellants have not provided persuasive evidence or argument explaining
why Challoner's teaching to use HPMC or gelatin in its capsules of dry
powder tobramycin would not be applicable when using capsules in
connection with Staniforth's dry powder formulation. Accordingly, we
affirm the Examiner's rejection of claims 30-32.
Claims 33 and 34
Claim 3 3 depends from claim 11, and further requires that
administration of the formulation from the capsule to the lungs of a subject
results in rapid delivery of the tobramycin and local absorption of the
tobramycin by the lungs of the subject. Claim 34 depends from claim 15,
and further requires that administration of the formulation from the capsule
to the lungs of a subject results in rapid delivery of the tobramycin and local
absorption of the tobramycin by the lungs of the subject. Appellants argue
that "Staniforth is directed to compositions in which systemic delivery of an
active material is achieved by delayed release of the active material" and
that this "would have led a skilled artisan away from a capsule that, upon
administration, results in rapid delivery of tobramycin and local absorption
of tobramycin by the lungs." App. Br. 42.
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For the reasons discussed above, we are not persuaded that concerns
regarding delivery speed and/or systemic administration would have led the
skilled artisan away from using tobramyacin in capsules produced using
Staniforth's mechano-fusion process. We agree with the Examiner that
because the machano-fused tobramyacin capsules suggested by Staniforth
and Challoner are identical to the claimed capsules, the skilled artisan
"would have expected the same properties" including rapid delivery. Ans.
13. In re Spada, 911 F.2d 705, 709 (Fed. Cir. 1990). Accordingly, we
affirm the Examiner's rejection of claims 33 and 34.
Claims 12 and 14
Claim 12 is directed to a method for preparing the capsule of claim
11. The method includes: (i) feeding particles of tobramycin and
magnesium stearate particles into a driven vessel of a Mechano-Fusion
apparatus, (ii) processing the particles of tobramycin and magnesium
stearate particles for a time of at least 2 minutes, to obtain microparticles,
(iii) collecting the microparticles, and iv) filling the microparticles into a
capsule. Claim 14 depends from claim 12, and further requires that the
processing is conducted for at least 5 minutes.
Appellants argue that "a skilled artisan would have been discouraged
from processing tobramycin with a mechano-fusion apparatus which makes
the particles experience '[]enough energy to locally heat and soften, break
... the particles."' App. Br. 43. We are not persuaded for the reasons
discussed above.
Appellants further argue: "While the examiner references disclosure
in Staniforth and Stein of applying mechano-fusion for times in excess of 2
minutes ( or 5 minutes), neither reference discloses applying mechano-fusion
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to a formulation including tobramycin." Id. at 43--44. We find this
argument unpersuasive because it fails to address the combined teachings of
Challoner, Staniforth, and Stein. See In re Merck & Co., 800 F.2d 1091,
1097 (Fed. Cir. 1986) ("Non-obviousness cannot be established by attacking
references individually where the rejection is based upon the teachings of a
combination of references.").
Claim 15
Claim 15 is directed to the treatment of a Pseudomonas aeruginosa
infection associated with cystic fibrosis, including administering an effective
amount of tobramycin from the capsule of claim 11 to a subject in need of
such treatment. Appellants argue that "[ t ]he examiner merely identifies
treatment of a Pseudomonas aeroginosa infection including administering
an effective amount of tobramycin in Challoner but does not address the
applicability of a formulation that is beyond the scope of Challoner (i.e., a
formulation including magnesium stearate) to such treatment." App. Br. 45.
We are not persuaded because Challoner discloses that the active ingredient,
tobramycin, can be used to treat endobronchial infection, which Challoner
defines to include Pseudomonas aeruginosa. Challoner ,r 56. Appellants
have not provided persuasive evidence or argument explaining why the
skilled artisan would not reasonably have expected this teaching to also
apply to a tobramycin formulation that includes magnesium stearate as an
additive. Accordingly, we affirm the Examiner's rejection of claim 15.
DECISION
For the reasons provided herein and those set forth in the Examiner's
Answer and Final Action, we affirm the Examiner's rejection of claims
18
Appeal2017-002010
Application 12/967 ,306
Claims 7, 8, 11, 12, 14, 15, and 28-34 under 35 U.S.C. § 103(a) as obvious
over the combination of Staniforth, Stein, and Challoner. We reverse the
Examiner's rejection of Claims 33 and 34 under 35 U.S.C. § 112 as
indefinite.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 4I.50(f).
AFFIRMED
19