MEXICHEM AMANCO HOLDING S.A. DE C.V.

Patent Trials and Appeals Board

Sep 23, 2020

2020001616 (P.T.A.B. Sep. 23, 2020)

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.
14/784,798 10/15/2015 Stuart Corr 9404.23122-PCT US 5697
26308 7590 09/23/2020
RYAN KROMHOLZ & MANION, S.C.
POST OFFICE BOX 26618
MILWAUKEE, WI 53226
EXAMINER
YU, HONG
ART UNIT PAPER NUMBER
1612
NOTIFICATION DATE DELIVERY MODE
09/23/2020 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):
RKMIPPatent@rkmiplaw.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
________________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
________________

Ex parte STUART CORR and
TIMOTHY JAMES NOAKES1
________________

Appeal 2020-001616
Application 14/784,798
Technology Center 1600
________________

Before FRANCISCO C. PRATS, JOHN G. NEW, and
DAVID COTTA, Administrative Patent Judges.

NEW, Administrative Patent Judge.

DECISION ON APPEAL

1 We use the term “Appellant” to refer to the “applicant” as defined in
37 C.F.R. § 1.142. Appellant identifies Mexichem Amanco Holding, S.A.
de C.V. as the real party-in-interest. App. Br. 3.
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Application 14/784,798

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SUMMARY
Appellant files this appeal under 35 U.S.C. § 134(a) from the
Examiner’s Final Rejection of claims 1–8 and 14–24. Specifically, claims
1–8 and 14–18 stand rejected as unpatentable under 35 U.S.C. § 103 as
being obvious over the combination of Lulla et al. (WO 2010/052466 A2,
May 14, 2010) (“Lulla”), Weers et al., (US 2010/0329984 A1, December 30,
2010) (“Weers”), and Daikin, HFC-152a, Product Information (May 2009)
(“Daikin”).
Claims 19–23 stand rejected as unpatentable under 35 U.S.C. § 103 as
being obvious over the combination of Lulla, Weers, and HFC-152a, and
Hoelz et al. (US 2009/0092559 A1, April 9, 2009) (“Hoelz”).
Claim 24 stands rejected as unpatentable under 35 U.S.C. § 103 as
being obvious over the combination of Lulla, Weers, and Berkel et al. (US
2007/0183982 A1, August 9, 2007) (“Berkel”).2
We have jurisdiction under 35 U.S.C. § 6(b).
We REVERSE.

NATURE OF THE CLAIMED INVENTION
Appellant’s claimed invention is directed to pharmaceutical
compositions suitable for delivery from a pressurized container, preferably
free of polar excipients and comprising: (a) a propellant component that
consists essentially of 1,1- difluoroethane (R-152a); (b) a surfactant

2 Claim 22 was also rejected by the Examiner as unpatentable under 35
U.S.C. § 112(b) as being indefinite. Final Act. 3. The Examiner has
withdrawn this rejection. Ans. 3.
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component; and (c) a drug component that consists of salbutamol sulfate,
which can be delivered using a metered dose inhaler (“MDI”). Abstr.

REPRESENTATIVE CLAIM
Claim 1 is representative of the claims on appeal and recites:
1. A pharmaceutical composition that is free of polar
excipients, said composition comprising:

(a) a propellant component consisting essentially of
1,1-difluoroethane (R-152a) propellant,

(b) a surfactant component consisting essentially of
polyvinylpyrrolidone surfactant; and

(c) a drug component consisting of solid drug particles
of salbutamol sulphate,

wherein the 1,1-difluoroethane propellant and
polyvinylpyrrolidone surfactant provide a propellant/surfactant
mixture in which the solid drug particles of salbutamol sulphate
are suspended, and

wherein the salbutamol sulphate and the
polyvinylpyrrolidone are included in the mixture with the
propellant as separate components.

App. Br. 13.

ISSUES AND ANALYSES
We decline to adopt the Examiner’s findings, reasoning, and
conclusion that the claims on appeal are prima facie obvious over the
combined cited prior art. We address the arguments raised by Appellant
below.
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Issue

Appellant argues that the Examiner erred because the combined
references neither teach nor suggest the limitation reciting “wherein the
salbutamol sulphate and the polyvinylpyrrolidone are included in the
mixture with the propellant as separate components.” App. Br. 6.

Analysis
The Examiner first construes the claim term “mixture” as including, in
its broadest reasonable interpretation consistent with Appellant’s
Specification, “any mixture, homogenous [or] non-homogenous.” Final Act.
5.
The Examiner finds that Lulla teaches aerosol compositions consisting
of: (1) at least one hydrofluoroalkane (“HFA”) propellant such as 1,1,1,2-
tetrafluoroethane (HFA-134a), 1,1,1,2,3,3,3-heptafluoropropane (HFA-227),
etc.; and (2) at least one active agent, such as salbutamol sulphate
complexed with an adjuvant such as PVP; (3) in a suitable MDI-pressurized
canister with a suitable valve. Final Act. 6. The Examiner points to
exemplified composition 5 of Lulla, which consists of 3.6 mg of active-PVP
100% complex and a propellant (with a 1:1 ratio between the active and
PVP). Id. (citing Lulla Abstr. and generally).
The Examiner finds, however, that Lulla does not expressly teach the
use of R-152a3, also an HFA, as a propellant. Final Act. 6. The Examiner
finds that Weers teaches pressurized aerosol compositions in metered dose

3 “R-152a” and “HFC-152a” both refer to 1,1, difluoroethane. See Weers ¶
20; Daikin, 1; Spec. 4.
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inhalers (“MDIs”) consisting of: (1) a medicament, including salts of
salbutamol; (2) a hydrofluorocarbon propellant such as HFA-134a, HFA-
227, R-152a, etc.; and (3) a surfactant. Final Act. 6 (citing Weems Abstr.,
¶¶ 20, 28, 30, 33–36, 77, 94, 95, 144–147,167, claims 1–4 and 10). The
Examiner finds that Weems teaches compositions containing salbutamol
sulfate4 in Example III. Id. The Examiner also points to Daikin, which the
Examiner finds teaches that HFC-152a has a lower global warming potential
compared to other fluorocarbons such as HFC-134a. Id.
The Examiner concludes that it would have been prima facie obvious
to a person of ordinary skill in the art to combine the teachings of Lulla,
Weers, and Daikin, by replacing HFA-134a or HFA-227 as a propellant, as
taught by Lulla, with R-152a. Final Act. 7. The Examiner finds that HFA-
134a, HFA-227, and R-152a are interchangeable as propellants for
delivering pressurized aerosol compositions in MDIs and, because HFC-
152a has a lower global warming potential compared to other fluorocarbons
such as HFC-134a, a skilled artisan would have been motivated to substitute
HFC-152a for the HFAs taught by Lulla. Id. The Examiner further
concludes that, absent any demonstration of unexpected result, it would have
been obvious to a skilled artisan to replace HFA-134a or HFA-227 with R-
152a, because such routine substitution would also yield predictable results.
Id.
Appellant argues that Lulla teaches that the pharmaceutical active
agent, which may apparently be salbutamol sulfate, is complexed with the

4 Except when directly quoting a reference or a brief, we employ herein the
American spelling of “sulfate.”
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adjuvant, such as polyvinylpyrrolidone (“PVP”). App. Br. 6. According to
Appellant, this complex is obtained by dissolving both the drug and the
adjuvant in a solvent system for those compounds followed by removal of
the solvent; the resulting solid complex is then dispersed in the HFA
propellant. Id. (citing Lulla 11). Appellant also points to the Declaration of
Dr. Stuart Corr5, filed September 7, 2018 (the “Corr Declaration”) in support
of this teaching of Lulla as being known in the art at the time of invention.
Id. (citing Corr Decl. ¶ 12). Appellant contends that it is evident from the
teachings of Lulla that the pharmaceutical active is dissolved in a suitable
solvent followed by the adjuvant and the resulting solution is then treated to
remove the solvent, leaving the solid drug-adjuvant complex behind. Id.
Appellant asserts that this dissolution is not possible with HFA propellants
such as R-152a (which is specifically recited in the claims), because
salbutamol sulfate has negligible solubility in HFA propellants. Id. (citing
Corr Decl. ¶ 15).
Appellant emphasizes that Lulla teaches that the PVP is complexed
with the drug and is not included in the composition as a distinct species, as
recited in the claims. App. Br. 6. Appellant contends that the claims also
require the solid drug particles of salbutamol sulfate to be dispersed or
suspended in the HFA-152a/PVP) mixture. Id. Appellant asserts that a
person of ordinary skill in the art would have understood that Appellant’s
claimed composition, in which the salbutamol sulfate and the PVP are
included in the mixture with the propellant as separate components, is

5 Dr. Corr is one of the named inventors of the claimed invention.
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inconsistent with Lulla’s teaching that the PVP is complexed with the
salbutamol sulfate. Id.
Appellant also points to Lulla’s teaching that:
The inventors further observed that the dispersion of surfactant
in the pharmaceutical aerosol composition with other
pharmaceutically acceptable excipients rendered the
composition unstable during the storage. In particular it was
observed that the fine particle mass does not remain [the] same
or decreases in timely manner during the storage. But, it was
surprisingly found that when the drug was complexed with an
adjuvant such as PVP K 25, PVP K 17 or PVP K[ ]30 etc., along
with the addition of propellant(s) or optionally with one or more
bulking agent and/or co-solvent(s), aggregation of fine drug
particles was reduced significantly and hence keeping the
composition stable during the storage period. It was also found
that the composition continued to exhibit uniform delivered dose
characteristics throughout the life of the MDI.

App. Br. 7 (quoting Lulla 6). Appellant thus asserts that Lulla expressly
teaches that unless a PVP/salbutamol sulfate complex is formed, the
resulting suspension will not be suitable, regardless of the propellant.
Therefore, Appellant argues, Lulla teaches away from the presently claimed
pharmaceutical composition in which the solid drug particles are suspended
in an HFA-152a propellant/PVP surfactant mixture. Id.
The Examiner replies that the limitation of claim 1 requiring that the
surfactant and drug “are included” in the mixture with the propellant “as
separate components” is a product-by-process limitation and reads on the
components being added at various timeframes. Ans. 4. More specifically,
the Examiner finds that the language of the claim does not exclude
salbutamol sulfate and PVP from being first combined to form a premix (i.e.,
the complex) and then being added to the propellant. Id.
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The Examiner invites us to compare the disclosures of Appellant’s
Specification and the teachings of Lulla. Specifically, the Examiner points
to pages 9–10 of the Specification, which discloses:
The pharmaceutical compositions of the invention can also be
prepared within the confines of a pressurised container, such as
an aerosol canister or vial, from which the compositions are
ultimately released as an aerosol spray using a medication
delivery device, such as a MDI. In this method, a weighed
amount of the salbutamol sulphate is introduced into the open
container. A valve is then crimped onto the container and the
152a-containing propellant component, in liquid form,
introduced through the valve into the container under pressure,
optionally after first evacuating the container through the valve.
The surfactant component can be mixed with the salbutamol
sulphate or, alternatively, introduced into the container after
the valve has been fitted, either alone or as a premix with the
propellant component. The whole mixture can then be
treated to disperse the drug in the propellant or
propellant/surfactant mixture, e.g.[,] by vigorous shaking or
using an ultrasonic bath. Suitable canisters may be made of
plastics, metal or glass.

(Emphasis added by Examiner). The Examiner notes that Lulla teaches:
The present invention further provides a process of
manufacturing a pharmaceutical aerosol dispenser for delivering
the aerosol pharmaceutical formulation to a patient in need
thereof, comprising:

(a) weighing the complexed drug particles in a suitable metal
canister,

(b) optionally mixing the complexed drug particles with one or
more suitable excipients selected from cosolvents, bulking
agents, antioxidants, lubricants and optionally with one or more
surfactants or with other similarly complexed or non-complexed
drugs,

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(c) crimping the canister with a suitable valve and charging
with HFA Propellant.

Lulla 11 (emphasis added by Examiner).
The Examiner therefore finds that Lulla teaches that the individual
components may be added in various sequences, individually or as premixes,
but, in both Lulla and the claims, one obtains a product which is a
salbutamol sulfate-PVP-propellant suspension. Ans. 5.
We find Appellant’s argument persuasive. As an initial matter, we do
not agree with the Examiner that the limitation reciting “wherein the 1,1-
difluoroethane propellant and polyvinylpyrrolidone surfactant provide a
propellant/surfactant mixture in which the solid drug particles of salbutamol
sulphate are suspended” is a product-by-process limitation, or, put more
accurately, a process limitation in a product claim. See SmithKline Beecham
Corp. v. Apotex Corp., 439 F.3d 1312, 1322 (Fed. Cir. 2006). The limitation
does not expressly or implicitly recite steps of a method or process by which
the composition is formed, or by which the limitation is a “structural” part of
the product (e.g., a molded plastic). Id. To the contrary, a plain reading of
the language of the limitation recites the component constituents of the
claimed composition, viz., an HFC-125a mixture in which the solid drug
particles of salbutamol sulfate are suspended, and in which the salbutamol
sulfate and the PVP are included in the mixture with the propellant as
separate components.
Furthermore, we do not interpret the claim language reciting “wherein
the salbutamol sulphate and the polyvinylpyrrolidone are included in the
mixture with the propellant as separate components” to recite that there is
any specific method or process for incorporating the salbutamol sulfate and
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the PVP into the composition. Rather, we interpret the claim language as
meaning that, in the composition, the salbutamol sulfate and the PVP exist
as separate components. We find that this is consistent with the preceding
limitation, which requires that the solid salbutamol sulfate particles be
suspended in the HFC-125a/PVP mixture.
We therefore construe the language of claim 1 as requiring that the
HFC-152a (i.e., the 1,1-difluoroethane) and the PVP surfactant are in a
mixture in which the solid drug particles of salbutamol sulfate are
suspended. The claim further requires that the salbutamol sulfate and the
PVP are included in the mixture as separate, i.e., discrete, components —
solid particles suspended in the HFC-125a/PVP mixture. Lulla is directed to
pharmaceutical aerosol compositions “comprising at least one
hydrofluoroalkane propellant; at least one active agent complexed with an
adjuvant; and, optionally, at least one pharmaceutically acceptable
excipient.” Lulla Abstr. (emphasis added). Lulla does not provide an
express definition of the term “complexed.” Lulla does, however, provide
examples of how the drug component (which can include salbutamol sulfate)
and the adjuvant (which can be PVP) are “complexed.” Specifically, Lulla
teaches:
In another aspect, the present invention provides a process of
manufacturing a complex of an active agent and an adjuvant
comprising:

(a) mixing the active agent in an organic solvent (e.g.
acetone),

(b) heating the mixture from step (a) to a suitable
temperature and adding water to form a clear solution;

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(c) adding the adjuvant to the above solution from step
(b);

(d) concentrating the clear solution under reduced
pressure, preferably under vacuum, to form a residue;

(e) washing the residue with the same solvent used in step
(a); and

(f) drying (for example at suitable temperature, or
preferably 50°C) the washed residue from step (e) to form a drug-
adjuvant complex.

The solvent used in the above process may be selected
from acetonitrile, methanol, water, dimethyl formamide,
acetone, tetrahydrofuran, dimethyl sulfoxide. Most preferable
solvent is acetone.

Alternatively, the complex of an active agent and an
adjuvant can be isolated by lyophilization or by flash-
evaporating the solvent using suitable techniques known in the
art such as spray-drying. Flash-evaporating technique with
respect to the present invention means removal of the solvent by
applying heat and vacuum.

Lulla 11–12. Lulla thus teaches dissolving the salbutamol sulfate and the
PVP in a heated organic solvent to form a clear solution, after which the
solvent is removed, either via concentration and drying or via lyophilization.
Appellant’s Specification teaches no comparable methods of forming
a salbutamol sulfate/PVP complex. Appellant’s Specification discloses that:
The pharmaceutical compositions of the invention can be
prepared by a simple blending operation in which the R-152a-
containing propellant component, the surfactant component, and
the salbutamol sulphate are mixed together in the required
proportions in a suitable mixing vessel. Mixing can be promoted
by stirring as is common in the art. Conveniently, the R-152a-
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containing propellant component is liquefied to aid mixing. If the
pharmaceutical composition is made in a separate mixing vessel,
it can then be transferred to pressurised containers for storage,
such as pressurised containers that are used as part of medication
delivery devices and especially MDIs.

Spec. 9 (emphasis added). The Specification also discloses:

The pharmaceutical compositions of the invention can also be
prepared within the confines of a pressurised container[…]. In
this method, a weighed amount of the salbutamol sulphate is
introduced into the open container. A valve is then crimped onto
the container and the 152a-containing propellant component, in
liquid form, introduced through the valve into the container
under pressure, optionally after first evacuating the container
through the valve. The surfactant component can be mixed with
the salbutamol sulphate or, alternatively, introduced into the
container after the valve has been fitted, either alone or as a
premix with the propellant component. The whole mixture can
then be treated to disperse the drug in the propellant or
propellant/surfactant mixture, e.g. by vigorous shaking or using
an ultrasonic bath.

Id. at 9–10 (emphasis added). Both of these methods thus employ simple
mixing (e.g., stirring, shaking) of the constituents. However, we can discern
no disclosure in the Specification that teaches “complexing” as provided for
in the teachings of Lulla.
The Examiner points to the teachings of Lulla at page 11, and quoted
supra, as supporting the finding that Lulla teaches that the individual
components may be “added in various sequences, individually or as
premixes.” See Ans. 5. We are not persuaded by this finding, because the
quoted portion of Lulla expressly states: “weighing the complexed drug
particles” and “optionally mixing the complexed drug particles with one or
more suitable excipients.” Lulla 11 (emphasis added). Lulla thus teaches
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that, in this process, the salbutamol sulfate particles have been previously
complexed with the PVP in a manner that is not consistent with the simple
“mixing” disclosed by Appellant’s Specification.
More importantly, the Examiner does not articulate any reason as to
why a person of ordinary skill in the art would have been motivated to
abandon the method of complexing the salbutamol sulfate with the PVP,
taught by Lulla as a central part of its invention, in favor of mere mixing,
stirring, or shaking as disclosed by the Specification. Furthermore, the
Examiner adduces no persuasive evidence that the complexing method of
Lulla would produce the same end result, viz., a “propellant/surfactant
mixture in which the solid drug particles of salbutamol sulphate are
suspended” as would the simple mixing of the constituents disclosed by
Appellant’s Specification. Absent any such reasoning or evidence, we are
unable to sustain the Examiner’s conclusion that the claims are prima facie
obvious over the combined cited prior art. Furthermore, because we find
that our conclusion in this respect is dispositive of this appeal, we do not
reach Appellant’s additional arguments.

CONCLUSION
The Examiner’s rejection of claims 1–8 and 14–24 under
35 U.S.C. § 103 is reversed.

REVERSED

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Claims
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
1–8, 14–18 103 Lulla, Weers,
HFC-125a

1–8, 14–18
19–23 103 Lulla, Weers,
HFC-125a, Hoelz
19–23
24 103 Lulla, Weers, and
Berkel
24
Overall
Outcome
1–8, 14–24