Ex Parte Stein

Patent Trials and Appeals Board

Apr 11, 2019

13515399 - (D) (P.T.A.B. Apr. 11, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
13/515,399 06/12/2012
32692 7590 04/15/2019
3M INNOVATIVE PROPERTIES COMPANY
PO BOX 33427
ST. PAUL, MN 55133-3427
FIRST NAMED INVENTOR
Stephen W. Stein
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.
66048US005 2623
EXAMINER
NGUYEN, JOHN P
ART UNIT PAPER NUMBER
1619
NOTIFICATION DATE DELIVERY MODE
04/15/2019 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):
LegalUSDocketing@mmm.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte STEPHEN W. STEIN
Appeal 2018-001102
Application 13/515,399
Technology Center 1600
Before ERIC B. GRIMES, JEFFREY N. FREDMAN, and
TA WEN CHANG, Administrative Patent Judges.
FREDMAN, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal 1,2 under 35 U.S.C. § 134 involving claims to a
metered dose inhaler containing an aerosol formulation. 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 the 3M Company (App.
Br. 2).
2 We have considered the Specification of December 8, 2010 ("Spec.");
Final Office Action of December 15, 2016 ("Final Act."); Appeal Brief of
May 15, 2017 ("App. Br."); Examiner's Answer of September 8, 2017
("Ans."); and Reply Brief of November 8, 2017 ("Reply Br.").
Appeal 2018-001102
Application 13/515,399
Statement of the Case
Background
"Metered Dose Inhalers (MDis) are widely used for the treatment of
respiratory diseases such as asthma, COPD, and allergic rhinitis. MDis use
high-pressure liquefied propellants to atomize the formulation into small
droplets capable of delivering drug into the regions of the respiratory tract
via oral or nasal inhalation" (Spec. 1: 10-13). "[T]wo key parameters that
influence the deposition characteristics into the respiratory tract are the mass
median aerodynamic diameter (MMAD) and the geometric standard
deviation (GSD) of the delivered aerosol" (id. at 1: 15-17).
The Claims
Claims 1, 3-10, 12, 13, and 22 are on appeal. Claim 1 is
representative and reads as follows:
1. A metered dose inhaler containing an aerosol formulation
compnsmg:
propellant;
at least one drug dissolved in the formulation;
at least one other drug in undissolved particulate form
suspended in the formulation and having a mass median
diameter of less than 1. 7 microns,
wherein the number of suspended drug particles is at
least 3 x 109 suspended particles per milliliter of formulation.
The Re} ection
The Examiner rejected claims 1, 3-10, 12, 13, and 22 under 35 U.S.C.
§ I03(a) as obvious over Oliver3 and Stein4 (Final Act. 3-8).
3 Oliver et al., US 2005/0207984 Al, published Sept. 22, 2005.
4 Stephen W. Stein, Estimating the Number of Droplets and Drug Particles
Emittedfrom MD!s, 9 AAPS PHARMSCITECH 112-15 (2008).
2
Appeal 2018-001102
Application 13/515,399
The Examiner finds Oliver teaches "a pharmaceutical aerosol
composition comprising particles of formoterol ... and a propellant" (Final
Act. 3). The Examiner finds Oliver teaches "the particles of formoterol have
a mass median diameter of including less than one micron" (id. at 4).
The Examiner acknowledges that "Oliver is silent in regards to the
number of suspended drug particles, e.g. at least 3xl09 suspended particles
per milliliter" (Final Act. 4).
The Examiner finds "Stein teaches that the mass of the drug
delivered to the patient is determined by the size and number of drug
particles delivered and that aerosols with smaller particles size distributions
have more particles per unit mass than aerosols with larger particles" (Final
Act. 5). The Examiner finds "Stein teaches that decreasing the particle size
by a factor of two results in an eightfold increase in the number of particles"
and that "the number of particles is highly dependent on ... the MMAD"
(id.).
The Examiner finds it obvious "to increase the number of drug
particles by ... decreasing the drug particle size of suspended drug
particles" because "an increase in number of drug particles provides more
particles per unit mass of delivery which enhances the efficacy of an inhaler
by increasing the amount of drug that penetrates into the respiratory tract"
(Final Act. 5).
The issue with respect to this rejection is: Does a preponderance of
the evidence of record support the Examiner's conclusion that Oliver and
Stein render the formulation of claims 1 and 12 obvious?
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Application 13/515,399
Findings of Fact
1. Oliver teaches "formulations of formoterol fumarate in
suspension and ciclesonide in solution at therapeutic effective concentrations
in HFA 134a and/or HFA 227 propellant" (Oliver ,r 14).
2. Oliver teaches:
Preferably formoterol constitutes about 0.06 to about
0.60 mg per ml .... The particles of formoterol are generally
micronized particles or particles processed by other methods,
preferably having a mass median diameter equal to or greater
than 1 micron, more particularly from 1 to 10 micron, even
more particularly from 1 to 5 micron. Smaller particles having a
mass median diameter of less than one micron may also be
suitable.
(Oliver ,r,r 37-38).
3. Oliver teaches "conventional dispensing valves, preferably
metered dose valves, can be used to deliver formulations of the invention"
(Oliver ,r 54).
4. Stein teaches
Metered dose inhalers (MD Is) are widely used for
treatment of diseases of the lung including asthma and chronic
obstructive pulmonary disease. In an MDI, drug is contained in
a formulation consisting of a liquefied propellant and optionally
cosolvent or other excipients such as surfactants. The drug may
be dissolved in the formulation or may consist of small particles
suspended in the formulation. Each time an MDI is actuated, a
precise quantity of formulation is atomized into fine droplets.
For solution MDis, each atomized droplet contains drug.
(Stein 112, col. 1 ).
5. Stein teaches the "size distribution of an MDI aerosol is a
critical parameter influencing the effectiveness of the inhaler since the
particle size distribution significantly influences the amount and location of
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Appeal 2018-001102
Application 13/515,399
deposition within the lung (4---6)" (Stein 112, col. 1). The title of reference 5
cited by Stein is "[b] eneficial effects with reduced particle size and CFC-free
extrafine aerosol steroid on lung deposition, absorption, efficacy and safety"
(see Stein 115, ref. 5).
6. Stein teaches that "[i]n addition to the particle size distribution,
the efficacy of an inhaler is related to the mass of drug in the MDI aerosol as
these two factors combine to determine the total amount of drug that
penetrates into the respiratory tract" (Stein 112, col. 1-2).
7. Figure 1 of Stein is reproduced below:
,,-..··
1oooor"/
,, •... ,, ....... ~,·
,,,···
fc_K "•"" 5
"Fig. 1. The number of drug particles, calculated using Eq. 6, in theoretical
MDI plumes containing 100 mcg of total drug mass" (Stein 113, col. 1).
"GSD is the geometric standard deviation of the size distribution" (Stein
113, co 1. 1).
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Appeal 2018-001102
Application 13/515,399
8. Stein teaches the "mass of drug delivered to the patient is
determined by the size and number of drug particles delivered. Since
smaller particles contain less mass than larger particles, aerosols with
smaller particle size distributions have more particles per unit mass than
aerosols with larger particles" (Stein 112, col. 2).
9. Stein teaches the "number of particles in MDI plumes varies by
approximately three orders of magnitude among various commercial
products and is highly dependent on the MMAD, GSD, and total mass of the
aerosol" (Stein 115, col. 2).
10. Stein teaches "for hypothetical MDI aerosols with MMADs
ranging from 1.0 to 5.0 µm and GSDs ranging from 1.3 to 2.0" that the
"number of particles ranged from approximately 2.37 million particles
(MMAD=5.0 µm; GSD=l.3) to approximately 1.89 billion particles
(MMAD=l.O µm; GSD=2.0)" (Stein 114, col. 1).
Principles of Law
"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'! Co. v. Teleflex Inc., 550 U.S. 398,416 (2007).
Analysis
We adopt the Examiner's findings of fact and conclusions of law (see
Final Act. 3-8; FF 1-10) and agree that Oliver and Stein render claims 1 and
12 obvious. We address Appellant's arguments below.
Claim 1
Appellant contends the rejection
attempts to present a case that Stein teaches that more particles
leads to greater efficacy, but that is not taught in Stein. Stein
merely teaches methodology to calculate the number of
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Application 13/515,399
particles being delivered. One needs to establish an appropriate
dose and an appropriate site of lung deposition for any
particular drug.
(App. Br. 4). Appellant further contends "[n]othing in the combination of
Oliver and Stein would lead one of skill in the art to the present claims,
namely that the number of suspended drug particles is at least 3xl09
suspended particles per milliliter of formulation prior to delivery" (App. Br.
5).
We find this argument unpersuasive because Stein expressly teaches
that the particle size distribution "significantly influences the amount and
location of deposition within the lung," citing a reference titled "[b ]eneficial
effects with reduced particle size and CFC-free extrafine aerosol steroid on
lung deposition, absorption, efficacy and safety" (FF 5). Thus, the ordinary
artisan would have been aware that smaller particles may result in superior
deposition into the lung, providing a reason to use smaller particles.
Because Stein also teaches that there is a relationship between particle size
and particle number, where smaller particles result in a larger number of
particles per unit mass (FF 7-8), we agree with the Examiner that the
ordinary artisan would have had reason to optimize particle size, and
consequently particle number, in order to improve delivery into desired lung
locations. We further note that Stein teaches that as the particle diameter
(MMAD) is reduced to 1 µm (I micron), the number of particles per
actuation is greater than 109 for particles with a size distribution having a
GSD over 1.7 (see FF 7).
Appellant contends that, based on the calculation in Stein, "arriving at
the feature of Claim 1 requires a selection of the smallest particle size in
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Application 13/515,399
Oliver, the highest concentration in Oliver, and the largest GSD in Stein"
(App. Br. 4).
While we appreciate Appellant's analysis, Appellant's own
calculation using the I micron value for MMAD and the 0.6 mg/ml
concentration, both directly taught by Oliver (FF 2) results in a particle
number falling within the scope of claim 1. This overlap results without any
optimization of particle size to smaller than 1 micron as suggested by Oliver
(see FF 2 "[ s ]maller particles having a mass median diameter of less than
one micron may also be suitable.") This overlap supports, rather than rebuts,
the Examiner's obviousness rejection. 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 primafacie case of obviousness.")
We recognize that Appellant contends that "one of skill in the art
would not look to that value as a reasonable GSD for the suspension
formulation in Oliver" (App. Br. 4), but this argument lacks factual support
because Stein teaches GSD values as high as 1.9 (FF 7) and Appellant lacks
evidence in rebuttal. "[ A ]ttomey argument [is] ... not the kind of factual
evidence that is required to rebut a prima facie case of obviousness." In re
Geisler, 116 F.3d 1465, 1470 (Fed. Cir. 1997).
Appellant contends "that controlling MMAD and/or GSD was the
problem being solved, which was not simply an exercise in optimization of
parameters" (Reply Br. 2).
We find this argument unpersuasive because the obviousness issue
depends on whether the prior art recognized the MMAD and GSD values as
optimizable, not whether Appellant "solved this problem, which, again, was
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Application 13/515,399
not simply an exercise in optimization of parameters" (Reply Br. 3). "[T]he
motivation in the prior art to combine the references does not have to be
identical to that of the applicant to establish obviousness." In re Kemps, 97
F.3d 1427, 1430 (Fed. Cir. 1996). In this case, Oliver demonstrates that both
the concentration of drug and the particle size are optimizable parameters
(FF 2) and Stein clearly shows that particle size and geometry, as
represented by MMAD and GSD, are optimizable parameters (FF 7).
"[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 (CCP A 1955).
To the extent that Appellant is arguing that the Specification
demonstrates something other than routine optimization, Appellant did not
timely provide any evidence of a secondary consideration such as
unexpected results that would, when considered with the prima facie
obviousness position, support a finding of non-obviousness.
Claim 12
Appellant separately argues "no values exist in Oliver and Stein that
could be selected to arrive at the claimed 'at least lxl010 suspended particles
per milliliter of formulation,' as included in claim 12" (Reply Br. 3).
We find this argument unpersuasive because Oliver expressly
suggests that the particle size can be less than 1 micron (FF 2), some of
which values would result in a number of particles as required by claim 12.
We agree with the Examiner that, based on the prior art (FF 5, 8), the
number of suspended drug particles in an aerosol composition
is an art-recognized result-effective variable, e.g., effects the
mass of suspended drug delivered to the patient which effects
efficacy of an inhaler, which a person of ordinary skill in the art
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Application 13/515,399
would routinely optimize. Optimization of parameters is a
routine practice that would be obvious for a person of ordinary
skill in the art to employ and reasonably would expect success.
It would have been customary for an artisan of ordinary skill to
determine the optimal number of suspended drug particles in an
aerosol composition in order to best obtain an aerosol
composition with desired a mass of suspended drug particles
delivered to a patient.
(Ans. 4).
Conclusion of Law
A preponderance of the evidence of record supports the Examiner's
conclusion that Oliver and Stein render the formulation of claims 1 and 12
obvious.
SUMMARY
We affirm the rejection of claims 1 and 12 under 35 U.S.C. § 103(a)
as obvious over Oliver and Stein. Claims 3-10, 13, and 22 fall with claims 1
and 12.
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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