Ex Parte Berkel et al

Patent Trial and Appeal Board

Mar 1, 2016

11668123 (P.T.A.B. Mar. 1, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
11/668,123 01129/2007
75410 7590 03/03/2016
Micheal P, Morris
Boehringer Ingelheim USA Corporation
900 Ridgebury Road
Ridgefield, CT 06877-0368
FIRST NAMED INVENTOR
Erhard Berke!
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.
01-2014 3291
EXAMINER
HAGHIGHATIAN, MINA
ART UNIT PAPER NUMBER
1616
NOTIFICATION DATE DELIVERY MODE
03/03/2016 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.e-Office.rdg@boehringer-ingelheim.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte ERHARD BERKEL,
HUBERT HOELZ, and FRIEDRICH SCHMIDT
Appeal2013-007050
Application 11/668, 123
Technology Center 1600
Before DEMETRA J. MILLS, JEFFREY N. FREDMAN, and
JACQUELINE T. HARLOW, 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
pharmaceutical preparation for propellant-driven metered-dose aerosols.
The Examiner rejected the claims as obvious and on the grounds of
obviousness-type double patenting. We have jurisdiction under 35 U.S.C.
§ 6(b). We affirm.
1 Appellants identify the Real Parties in Interest as Boehringer
Ingelheim International GMBH (see App. Br. 2).
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Application 11/668, 123
Statement of the Case
Background
"The present invention relates to new pharmaceutical formulations for
aerosols with at least two or more active substances together with at least
one surfactant for inhalative or nasal application" (Spec. 1, 11. 8-10).
The Claims
Claims 1-14, 21, 23, and 30 are on appeal. Independent claim 1 is
representative and reads as follows:
1. A pharmaceutical preparation for propellant-driven
metered-dose aerosols having a fluorinated hydrocarbon (HF A)
as propellant, which contains a combination of two or more
active substances, wherein at least one active substance is
present in dissolved form as well as at least one other active
substance in the form of suspended particles together with at
least one surfactant, the active substance present in dissolved
form being ipratropium bromide monohydrate, the active
substance present in the form of suspended particles being
salbutamol sulphate ( albuterol sulphate), the surfactant being
polyoxyethyleneglycerol trioleate, wherein the preparation does
not contain water, wherein the surfactant is present in a
concentration of 0.02% - 0.2% based on the mass of
surfactant/mass of the formulation as a whole (m/m).
The Issues
A. The Examiner rejected claims 1-14, 21, 23, and 30 under 35 U.S.C.
§ 103(a) as obvious over McNamara '2982 and Chen3 (Ans. 6-8).
B. The Examiner rejected claims 1-14, 21, 23, and 30 under 35 U.S.C.
§ 103(a) as obvious over McNamara '4644 and Geller5 (Ans. 8-10).
2 McNamara et al., US 6,423,298 B2, issued July 23, 2002.
3 Chen et al., US 2004/0092428 Al, published May 13, 2004.
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C. The Examiner rejected claims 1-14, 21, 23, and 30 under 35 U.S.C.
§ 103(a) as obvious over Lulla,6 McNamara '464, and Chen (Ans. 10-13).
D. The Examiner rejected claims 1-14, 21, 23, and 30 on the ground of
nonstatutory obviousness-type double patenting over claims 1-21 of US
6,423,298 and Chen (Ans. 14--15).
Because the same issues are dispositive for all of the rejections, we
will consider the rejections together.
The Examiner relies upon McNamara '298, McNamara '464, or the
claims of McNamara '298 to teach pharmaceutical aerosols comprising
salbutamol suspensions with dissolved ipratropium bromide that include a
poyoxyethylene surfactant (Ans. 6; cf Ans. 8, 14). The Examiner
acknowledges that these references "lack[] disclosure on the specific species
of polyoxyethylenes" (Ans. 7, 9) and relies on Chen, Geller, or Lulla to
suggest the polyoxyethyleneglycerol trioleate surfactant in pharmaceutical
formulations including aerosols (Ans. 7; cf Ans. 9, 11, 15). The Examiner
finds the "motivation for substituting them flows from their having been
used in the prior art, and from their being recognized in the prior art as
useful for the same purpose" (Ans. 7; cf Ans. 10, 12, 15).
The issue with respect to these rejection is: Does the evidence of
record support the Examiner's conclusion that the prior art renders the
claims obvious?
4 McNamara et al., WO 99/65464 Al, published Dec. 23, 1999.
5 Geller et al., US 3,632,743, issued Jan. 4, 1972.
6 Lulla et al., WO 2004/019985 Al, published Mar. 11, 2004.
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Application 11/668, 123
Findings of Fact
1. McNamara '298 teaches "stable aerosol formulations with
fluorohydrocarbons as propellants, particularly TG 134a and/or TG 227,
consisting of two or more active substances, wherein at least one active
substance is formulated as a solution and at least one active substance is
formulated as a suspension" (McNamara '298, col. 2, 11. 21-26; McNamara
'298, col. 4, claims 1, 3; cf McNamara '464 3, 11. 30-35).
2. McNamara '298 teaches that a "preferred embodiment contains
dissolved ipratropium bromide, particularly combined with salbutamol
sulphate (albuterol sulphate) as the suspended active substance" (McNamara
'298, col. 2, 11. 60-63; McNamara '298, col. 6, claim 21; cf McNamara '464
4, 1. 35 to 5, 1. 2).
3. McNamara '298 teaches that "[s]uitable surfactants and
suspension-stabilising agents include ... polyoxyethylenes ... The quantity
of surfactant may be up to 1: 1 based on the proportion by weight of the
suspended active substances; amounts of0.0001:1to0.5:1 are preferred,
whilst amounts of from 0.0001:1to0.25:1 are particularly preferred"
(McNamara '298, col. 3, 11. 16-36; McNamara '298, col. 5, claim 14; cf
McNamara '464 5, 1. 27 to 6, 1. 12).
4. Example 1 of McNamara '298 teaches the inclusion of"0.05%
by weight of surfactant" of oleic acid in a solution comprising the propellant
TG 134a, dissolved ipratropium bromide, and suspended salbutamol
sulphate (McNamara '298, col. 4, 11. 23-30; cf McNamara '464 8, 11. 5-12).
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5. Lulla teaches "a pharmaceutical composition comprising any
one of the following combinations of therapeutic agents ... (ix) salbutamol,
budesonide and ipratropium" (Lulla 3).
6. Lulla teaches "a propellant-containing dosage aerosol ... the
formulation may consist of a surface-active agent to stabilize the formulation
.... Preferred surfactants for use ... [include] oleic acid ... sorbitol
trioleate .... the surface-active agents are preferably used in the
formulations in the ratio of 0.00002 wt% ... to 20 wt% of the active
ingredients" (Lulla 5).
7. Example 21 of Lulla teaches a pharmaceutical composition
comprising salbutamol, ipratropium, and 0.02% of the surfactant oleic acid
with the propellant HFA134a (see Lulla 18).
8. Chen teaches "a pharmaceutical formulation capable of being
administered orally as discrete pharmaceutical unit dosage forms, each
containing a predetermined amount of the active ingredients, such as ...
aerosols sprays" (Chen i-f 60).
9. Chen teaches that "'surfactant of the invention' refer to a
compound including, but not limited to ... oleic acid ... Tagat TO
(polyoxyethylene glycerol trioleate )" (Chen i-f 45).
10. Chen teaches that the "pharmaceutical formulation comprises
about 5% to about 90% by volume of surfactant" (Chen i-f 82).
11. Geller teaches that "[ s ]uitable non-aqueous suspending agents
or solvents are those which are pharmacologically acceptable ... such as
oleic acid esters ... 'Labrafil M 2735' ... 'Labrafil M 2735' is
polyoxyethylene-glycerol trioleate" (Geller, col. 1, 11. 35---69).
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Principles of Law
"[W]hen a patent claims a structure already known in the prior art that
is altered by the mere substitution of one element for another known in the
field, the combination must do more than yield a predictable result". KSR
Int'! Co. v. Teleflex Inc., 550 U.S. 398, 416-417 (2007).
An "[ e ]xpress suggestion to substitute one equivalent for another need
not be present to render such substitution obvious." In re Fout, 675 F.2d
297, 301 (CCP A 1982).
Analysis
We adopt the Examiner's findings of fact and reasoning regarding the
scope and content of the prior art (Ans. 6-13; FF 1-10). We address
Appellants' arguments below.
Appellants contend that "Chen does not disclose that the
concentration of polyoxyethylene glycerol trioleate can be below 5%, which
is more than an order of magnitude greater than the upper limit of the
claimed range" (Br. 5). Appellants contend that the "formula of Geller
includes suspending agents at a very high concentration, specifically, the
combination of Miglyol and benzyl alcohol in examples 3 and 4 is 18.6%
and 19.9% respectively, by mass" (Br. 5).
We do not find these arguments persuasive because they fail to
combine the teachings of Chen and Geller with the teachings of McNamara
'298, McNamara '464, or Lulla. The primary references, McNamara '298,
McNamara '464, and Lulla, each teach surfactant ranges that fully overlap
the claimed range of 0.2% to 0.2% (FF 3, 6) for specific pharmaceutical
preparations that include the combination of salbutamol and ipratropium
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(FF 2, 5). Moreover, McNamara '298 and McNamara '464 exemplify 0.5%
surfactant (FF 4) while Lulla exemplifies 0.02% surfactant (FF 7), both
values within the claimed range. 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.")
We agree with the Examiner that the ordinary artisan would have
reasonably selected surfactant concentrations from the ranges and examples
of McNamara '298, McNamara '464, and Lulla for surfactants in aerosols of
salbutamol and ipratropium (FF 3, 6), when using known equivalent
surfactants such as the polyoxyethylene glycerol trioleate surfactant
disclosed by Chen or Geller (FF 9, 11). See In re Keller, 642 F.2d 413, 425
( CCP A 19 81) ("The test for obviousness is not whether the features of a
secondary reference may be bodily incorporated into the structure of the
primary reference . . . . Rather, the test is what the combined teachings of
the references would have suggested to those of ordinary skill in the art.")
Appellants contend that "[b ]ecause of the significant difference in
amounts of surfactant used, a person of ordinary skill in the art considering
Chen would not think that such a drastic modification would result in a
formulation that could still effectively deliver active agents to a nasal cavity"
(Br. 5). Appellants contend that the "Office Action has not considered the
portions of Chen and Geller that definitively lead a person of ordinary skill
in the art away from including the surfactant polyoxyethylene glycerol
trioleate in a concentration of 0.02% - 0.2%" (Br. 7).
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We find this argument unpersuasive because McNamara '298,
McNamara '464, and Lulla each teach selection of surfactant amounts
overlapping the claimed range for metered-dose aerosol delivery of the
specific agents required by claim 1 (FF 1-7). Appellants do not identify any
teaching that criticizes, discourages, or discredits the use of surfactants in the
amounts disclosed by McNamara '298, McNamara '464, and Lulla. See In
re Fulton, 391 F.3d 1195, 1201 (Fed. Cir. 2004) ("The prior art's mere
disclosure of more than one alternative does not constitute a teaching away
from any of these alternatives because such disclosure does not criticize,
discredit, or otherwise discourage the solution claimed").
Instead, Appellants simply identified specific embodiments in Chen or
Geller. However, disclosed examples and preferred embodiments do not
constitute a teaching away from a broader disclosure or non-preferred
embodiments. In re Susi, 440 F.2d 442, 446 n.3 (CCPA 1971). Here, the
general embodiments of Chen and Geller do not teach away from the very
specific disclosures of metered-dose aerosol delivery by McNamara '298,
McNamara '464, and Lulla.
Appellants contend that "[b ]ased on the Office Actions reasoning, any
reference at all that states polyoxyethylene glycerol trioleate is a surfactant,
would render the present claim unpatentable in view of McNamara '298.
This position is untenable and contrary to law" (Br. 6).
We disagree. The Examiner is not relying on any reference teaching
polyoxyethylene glycerol trioleate, but rather on Chen's teaching that this
surfactant is a known equivalent surfactant that may be used in
pharmaceutical aerosol sprays (FF 8-9) and on Geller' s teaching that this
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surfactant is a known equivalent that is pharmacologically acceptable (FF
11).
Indeed, the Examiner specifically recognizes the equivalence of
"surfactants such as poloxyethylenes and oleic acid" (Ans. 9), a finding well
supported by the teaching of oleic acid as a surfactant in each of the prior art
references (FF 4, 6, 9, 11) and the specific inclusion of both oleic acid and
polyoxyethylene glycerol trioleate as equivalent surfactants in Chen and
Geller (FF 9, 11 ). See Wm. Wrigley Jr. Co. v. Cadbury Adams USA LLC,
683 F.3d 1356, 1364 (Fed. Cir. 2012) ("This case presents a strong case of
obviousness based on the prior art references of record. [The claim] recites a
combination of elements that were all known in the prior art, and all that was
required to obtain that combination was to substitute one well-known ...
agent for another.")
Appellants contend that the "Office Action does not proffer, since
there is no reasonable expectation of success, why a skilled artisan would
expect that combining the primary references with the secondary references
and then drastically reducing the surfactant concentrations would result in a
successful pharmaceutical preparation" (Br. 7).
We are not persuaded. McNamara '298, McNamara '464, and Lulla
provide a very reasonable expectation of success in formulating salbutamol,
ipratropium and a surfactant where the surfactant falls within their disclosed
concentration ranges (FF 3, 6) or the 0.05% specific value disclosed by
McNamara '298 McNamara '464 (FF 4) or the 0.02% specific value
disclosed by Lulla (FF 7). Chen and Geller provide a reasonable expectation
of success is using polyoxyethylene glycerol trioleate in pharmaceutical
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preparations such as those of McNamara '298, McNamara '464, and Lulla
(FF 1-11 ). This reasoning is consistent with Kubin, which stated that
"[r]esponding to concerns about uncertainty in the prior art influencing the
purported success of the claimed combination, this court [in O'Farrell]
stated: ' [ o ]bviousness does not require absolute predictability of success ...
all that is required is a reasonable expectation of success."' In re Kubin, 561
F.3d 1351, 1360 (Fed. Cir. 2009) (citing In re O'Farrell, 853 F.2d 894, 903-
904 (Fed. Cir. 1988)).
Conclusion of Law
The evidence of record supports the Examiner's conclusion that the
prior art renders the claims obvious.
SUMMARY
In summary, we affirm the rejection of claim 1 under 35 U.S.C.
§ 103(a) as obvious over McNamara '298 and Chen. Claims 2-14, 21, 23,
and 30 fall with claim 1. 37 C.F.R. § 41.37(c)(l)(iv).
We affirm the rejection of claim 1under35 U.S.C. § 103(a) as
obvious over McNamara '464 and Geller. Claims 2-14, 21, 23, and 30 fall
with claim 1. 37 C.F.R. § 41.37(c)(l)(iv).
We affirm the rejection of claim 1under35 U.S.C. § 103(a) as
obvious over Lulla, McNamara '464, and Chen. Claims 2-14, 21, 23, and
30 fall with claim 1. 37 C.F.R. § 41.37(c)(l)(iv).
We affirm the rejection of claim 1 on the ground of nonstatutory
obviousness-type double patenting over claims 1-21 of US 6,423,298 and
Chen. Claims 2-14, 21, 23, and 30 fall with claim 1. 37 C.F.R.
§ 41.37(c)(l)(iv).
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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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