Ex Parte Maus et al

Board of Patent Appeals and Interferences

Apr 28, 2010

11485486 (B.P.A.I. Apr. 28, 2010)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
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Ex parte JOACHIM MAUS, PETER JURGEN CNOTA,
ISTVAN SZELENYI, and BEATRIX FYRNYS
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Appeal 2009-0011475
Application 11/485,486
Technology Center 1600
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Decided: April 28, 2010
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Before DONALD E. ADAMS, RICHARD M. LEBOVITZ, and
FRANCISCO C. PRATS, Administrative Patent Judges.

LEBOVITZ, Administrative Patent Judge.

DECISION ON APPEAL
This is a decision on an appeal under 35 U.S.C. § 134 by the Patent
Applicant from the Patent Examiner’s rejections of claims 21, 25-32, and
35-39 in U.S. Patent Application No. 11/485,486. The Board’s jurisdiction
for this appeal is under 35 U.S.C. § 6(b). The rejections are affirmed.

Appeal 2009-011475
Application 11/485,486

STATEMENT OF THE CASE
The claims are directed to a combination of R,R-glycopyrrolate and
Roflumilast for treatment of respiratory diseases, such as asthma and chronic
obstructive pulmonary disease (COPD).
The only pending claims in the application are claims 21, 25-32, and
35-39. The claims stand rejected by the Examiner as follows:
1) Claims 21, 25-32, and 35-39 under 35 U.S.C. § 103(a) as obvious
in view of Bannister (US Published Pat. App. 2003/0068280 A1, Apr. 10,
2003) and Amschler (US Pat. No. 5,712,298, Jan. 27, 1998); and
2) Claims 21, 25-32, and 35-371 on the grounds of nonstatutory
obvious-type double patenting as obvious in view of claims 1-3, 5, 6, 8, and
12-18 of copending US App. Serial No. 11/642,967 (Ans. 3).
Appellants did not argue the claims separately. We select claim 21 as
representative to decide both rejections in the appeal and the remaining
claims stand or fall with claim 21. 37 C.F.R. § 41.37(c)(1)(vii).
21. A combination of topical R,R-glycopyrrolate or a
physiologically acceptable salt thereof with Roflumilast or a
physiologically acceptable salt thereof for the treatment of
respiratory diseases, including bronchial asthma and chronic
obstructive pulmonary disease (COPD).

1 In the Examiner’s Answer, the Examiner listed the rejected claims as
claims 21, 25-32, and 35-39. However, in the Final Office action, claims 38
and 39 were not included in the statement of the rejection, and consequently
Appellants did not address these as rejected in their Appeal Brief. As the
Examiner did not state that a new grounds of rejection was made over
claims 38 and 39, we have treated their inclusion in the double patenting
rejection as an error.
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Application 11/485,486

OBVIOUSNESS OVER BANNISTER AND AMSCHLER
Statement of the Issues
The issues in this rejection are as follows:
• Whether Appellants provided adequate rebuttal evidence to establish
nonobviousness of the claimed combination of R,R-glycopyrrolate and
Roflumilast; and
• Whether the prior art would reasonably have suggested the claimed
“combination” comprising R,R-glycopyrrolate.

Principles of Law
The question of obviousness is resolved on the basis of underlying
factual determinations including: (1) the scope and content of the prior art;
(2) the level of ordinary skill in the art; (3) the differences between the
claimed invention and the prior art; and (4) secondary considerations of
nonobviousness, if any. Graham v. John Deere Co., 383 U.S. 1, 17-18
(1966).
“Often, it will be necessary . . . to look to interrelated teachings of
multiple [references] . . . and the background knowledge possessed by a
person having ordinary skill in the art, all in order to determine whether
there was an apparent reason to combine the known elements in the fashion
claimed.” KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007). “[T]his
analysis should be made explicit,” and it “can be important to identify a
reason that would have prompted a person of ordinary skill in the relevant
field to combine the elements in the way the claimed new invention does.”
Id.
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Once prima facie obviousness has been established, an applicant for a
patent can rebut it with
a showing of “unexpected results,” i.e., to show that the
claimed invention exhibits some superior property or advantage
that a person of ordinary skill in the relevant art would have
found surprising or unexpected. The basic principle behind this
rule is straightforward – that which would have been surprising
to a person of ordinary skill in a particular art would not have
been obvious.
In re Soni, 54 F.3d 746, 750 (Fed. Cir. 1995).
The unexpected results must also be “commensurate in scope with the
degree of protection sought by the claimed subject matter.” In re Harris,
409 F.3d 1339, 1344 (Fed. Cir. 2005).

Claim Interpretation
Claim 21 is drawn to a “combination of topical R,R-glycopyrrolate or
a physiologically acceptable salt thereof with Roflumilast or a
physiologically acceptable salt thereof for the treatment of respiratory
diseases.” While the claim expressly requires the presence of the R,R-
enantiomer, we discern no language in the claim that would limit the
combination to only R,R-glycopyrrolate. Rather, absent an express
definition in the Specification, we interpret the term “combination” to have
its ordinary and customary meaning,2 i.e., “a collection of things.”3 Thus,

2 The words in a claim “are generally given their ordinary and customary
meaning.” Vitronics Corp. v. Conceptronic, Inc., 90 F.3d 1576, 1582 (Fed.
Cir. 1996). The “ordinary and customary meaning of a claim term is the
meaning that the term would have to a person of ordinary skill in the art in
question at the time of the invention, i.e., as of the effective filing date of the
patent application.” Phillips v. AWH Corp., 415 F.3d 1303, 1313 (Fed. Cir.
2005). “[A] person of ordinary skill in the art is deemed to read the claim
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we construe the claimed combination to be open-ended and not restricted to
the two pharmaceutical agents listed in the claim. Consequently, while R,R
glycopyrrolate must be present in the combination, other ingredients are
permitted by the claim language, including other glycopyrrolate
enantiomers.

Scope and content of the prior art
In making an obvious determination, we must first identify the scope
and content of the prior art. Graham, 383 U.S. at 17. The following
numbered findings of fact (“FF”) summarize the prior art relied upon by the
Examiner in setting forth the basis of the rejection (Ans. 3):
Bannister
1. Bannister describes a pharmaceutical composition for pulmonary
delivery comprising glycopyrrolate (Bannister, 1: ¶ 11).
2. The “glycopyrrolate can be used to treat airway disease, particularly
COPD, asthma or cystic fibrosis.” (Id. at 2: ¶ 22.)
3. “Any suitable pharmaceutically effective drug which is used for the
treatment of a respiratory disease may also be co-administered with the
glycopyrrolate compositions of the invention.” (Id. at 2-3: ¶ 33.)
4. Among the list of additional therapeutics that can be administered
with glycopyrrolate are “PDE4 inhibitors” (id. at 3: ¶ 34).
term not only in the context of the particular claim in which the disputed
term appears, but in the context of the entire patent, including the
specification.” Id.
3 http://wordnetweb.princeton.edu/perl/webwn?s=combination. Retrieved,
April 16, 2010.
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5. “Glycopyrrolate has two stereogenic centres and hence exists in four
isomeric forms. Each individual isomer may be delivered to optimise the
efficacious effect of the drug, and reduce systemic exposure to those isomers
that are responsible for systemic side-effects.” (Id. at 3: ¶ 36.)
6. “A formulation of active isomers may be used, in which the ratio of
isomers is 1:1, or less than 1:1. Alternatively, the formulation of active
isomers is non-racemic, or the formulation ensures that the of [sic] active
isomers are delivered at different rates.” (Id. at 3: ¶ 37.)
Amschler
7. Amschler describes
cyclic nucleotide phosphodiesterass [sic, phosphodiesterase]
(PDE) inhibitors (specifically of type IV) . . . suitable on the
one hand as bronchial therapeutics (for the treatment of airway
obstructions on account of their dilating action but also on
account of their respiratory rate- or respiratory drive-increasing
action), but on the other hand especially for the treatment of
disorders, in particular of an inflammatory nature, e.g. of the
airways (asthma prophylaxis)

(Amschler, col. 11, ll. 34-42).
8.
On account of their PDE-inhibiting properties, the compounds
according to the invention can be employed in human and
veterinary medicine as therapeutics, where they can be used, for
example, for the treatment and prophylaxis of the following
illnesses: acute and chronic (in particular inflammatory and
allergen-induced) airway disorders of varying origin
(bronchitis, allergic bronchitis, bronchial asthma)

(id. at col. 11, 52-59).
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9. Amschler describes Roflumilast as one of its PDE4 (PDE, type IV)
inhibitors (Ans. 5; Amschler, col. 9, l. 40).

Differences between the prior art and the claimed invention
Once the scope and content of the prior art has been determined, the
next step is to identify the differences between the prior art and the claimed
invention. Graham, 383 U.S. at 17. The following numbered findings of fact
are pertinent to this issue:
10. Claim 21 is directed to a “combination” of “R,R-glycopyrrolate or a
physiologically acceptable salt thereof” and “Roflumilast.”
11. As found by the Examiner and supported by the evidence, Bannister
describes a composition comprising glycopyrrolate isomers as in claim 21,
which can be co-administered with PDE4 inhibitors, but which are not
specifically combined with Roflumilast (Ans. 5; FF1-6).
12. However, Amschler describes Roflumilast as a PDE4 inhibitor (Ans.
5; FF9).

Reason to combine the prior art
After ascertaining the differences between the prior art and the
claimed invention, the next step is to identify a reason why persons of
ordinary skill in the art would have been prompted to combine the prior art
to have made the claimed invention. KSR, 550 U.S. at 418. The following
findings are relevant to this determination:
13. Persons of ordinary skill in the art would have been prompted to have
combined glycopyrrolate and Roflumilast, each which were described as
effective for respiratory diseases (“airway disorders”), in view of Bannister’s
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teaching that any effective drug which is used for the treatment of a
respiratory disease may be co-administered with the Bannister
glycopyrrolate compositions (FF3).
14. “[O]ne skilled in the art would have assumed the combination of two
individual agents, each well-known to treat a respiratory disease such as
bronchial asthma and chronic obstructive pulmonary disease (COPD) into a
single composition would give an additive effect in the absence of evidence
to the contrary.” (Ans. 6.)
Analysis
Appellants contend that the “present invention is based on the
synergistic influence of R,R,-glycopyrrolate on the anti-inflammatory
activity of PDE4 inhibitors as shown in the examples of the present
application.” (App. Br. 5.) Citing evidence described in the Specification,
Appellants argue that the “anti-inflammatory effect of the PDE4 inhibitor
rolipram [a PDE4 inhibitor] is significantly enhanced by R,R glycopyrrolate
(page 7).” (Id.) R,R-glycopyrrolate alone did not influence the LPS-
induced TNF-α release (id.; Spec. 7). However, when combined with
rolipram, R,R-glycopyrrolate “significantly and surprisingly in an
overadditive manner” enhanced rolipram’s activity (Spec. 7).
A patent applicant can rebut a prima facie case of obviousness by a
showing of “’unexpected results.’” In re Soni, 54 F.3d at 750. The showing
of unexpected results must be factual; argument or conclusory statements do
not suffice. In re Geisler, 116 F.3d 1465, 1470 (Fed. Cir. 1997).
Unexpected results must be commensurate with the scope of the claim.
Harris, 409 F.3d at 1344.
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In this case, as pointed out by the Examiner, the rebuttal evidence
provided by Appellants was for one PDE4 inhibitor, rolipram, in
combination with R,R-glycopyrrolate. Rolipram is not covered by claim 21.
Rather, claim 21 recites a different compound, “Roflumilast.” Therefore,
the issue is whether persons of ordinary skill in the art would have believed
that “overadditive” and synergistic results would have been obtained with
Roflumilast and R,R-glycopyrrolate based on the results with rolipram and
R,R-glycopyrrolate.
Appellants have not given a logical reason or explanation as to why
the skilled worker, seeing the alleged synergy with rolipram and R,R-
glycopyrrolate, would have reasonably expected that such “surprising” result
would be obtained for a different combination of therapeutic agents.
Consequently, the data on page 7 of the Specification is insufficient to rebut
the Examiner’s determination that the claimed combination of Roflumilast
and R,R-glycopyrrolate would have been obvious to a person of ordinary
skill in the art.
Appellants also contend that there “is no suggestion in the cited prior
art that would lead a skilled artisan to the use of R,R,-glycopyrrolate.”
(App. Br. 6.)
Claim 21 is not limited to R,R-glycopyrrolate. The properly
interpreted claim is open to the inclusion of other glycopyrrolate
enantiomers, and is not restricted to only the R,R-form. Consequently, to
meet the claim limitation, it was necessary that the prior art taught the use of
glycopyrrolate enantiomers that included R,R,-glycopyrrolate, as the
Examiner concluded it did, and Appellants did not dispute.

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Application 11/485,486

OBVIOUSNESS TYPE DOUPLE-PATENTING
Claims 1-3 of copending application 11/642,967 read as
follows:
1. A combination of at least three different pharmaceutically
active substances or their physiologically acceptable salts
selected from the group consisting of anticholinergics, PDE4
inhibitors, glucocorticoids, B2-adrenoceptor agonists and
Leukotriene-receptor antagonists for the treatment of
inflammatory diseases.

2. The combination according to claim 1 wherein the
anticholinergic is racemic glycopyrrolate, one of its
enantiomers, one of its diastereoisomers or their physiologically
acceptable salts or a mixture thereof.

3. The combination according to claim 1 wherein the PDE4
inhibitor is selected from the group consisting of rolipram,
roflumilast, cilomilast, AWD-12-281 and their physiologically
acceptable salts.

Analysis
The Examiner found that copending Application Serial No.
11/642,967 disclosed the claimed combination of Roflumilast and R,R-
glycopyrrolate (Ans. 3). Appellants contend that the Examiner erred
because
copending ‘967 application requires at least three different
pharmaceutically active substances selected from the group
consisting of anticholinergics, PDE4 inhibitors, glucocorticoids,
β2-adrenoceptor agonists and Leukotiene-receptor antagonists.
It is respectfully submitted that it would not have been obvious
to select from this large list of possibilities the presently
claimed combination, topical R,R-glycopyrrolate and
Roflumilast.
(App. Br. 4.)
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Claim 2 of the copending application is directed to a glycopyrrolate.
Claim 3 is to a list of four different PDE4 inhibitors; the instantly claimed
Roflumilast is one of the four. To have made the claimed invention, a
person of ordinary skill in the art would have had to select the glycopyrrolate
of claim 2 as the anticholinergic of claim 1; and Roflumilast from the list of
four compounds of claim 3 as the PDE4 inhibitor of claim 1, an easily
traversed and small number of choices. Anticholinergics and PDE4
inhibitors are among a list of only five classes of therapeutic agents recited
in copending claim 1, and as three of the classes are required to be present in
the claim, the choice is limited and all combinations, could be easily written
out by the ordinary skilled worker by following the pattern of preferences
reflected in claims 2 and 3.

SUMMARY
The obviousness rejections of claim 21 under section 103 and
nonstatutory double-patenting are affirmed. Claims 25-32 and 35-39 fall
with claim 21.

TIME PERIOD FOR RESPONSE
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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