MERZ PHARMA GmbH & CO. KGaA

Patent Trials and Appeals Board

Dec 21, 2020

2020001829 (P.T.A.B. Dec. 21, 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.
15/008,646 01/28/2016 Hans-Joerg MOEBIUS MERZ 36 US DIV CONT 3 1083
25666 7590 12/21/2020
THE FIRM OF HUESCHEN AND SAGE
SEVENTH FLOOR, KALAMAZOO BUILDING
107 WEST MICHIGAN AVENUE
KALAMAZOO, MI 49007
EXAMINER
OLSON, ERIC
ART UNIT PAPER NUMBER
1623
MAIL DATE DELIVERY MODE
12/21/2020 PAPER
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.
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte HANS-JOERG MOEBIUS
____________

Appeal 2020-001829
Application 15/008,646
Technology Center 1600
____________

Before DONALD E. ADAMS, RICHARD M. LEBOVITZ, and
ULRIKE W. JENKS, Administrative Patent Judges.

ADAMS, Administrative Patent Judge.

DECISION ON APPEAL
Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from Examiner’s
decision to reject claims 1–11 (see Appeal Br. 3; Reply Br.2 2). We have
jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.

1 We use the word “Appellant” to refer to “applicant” as defined in 37
C.F.R. § 1.42. Appellant identifies the real party in interest as MERZ
PHARMA GMBH & CO. KGAA of Frankfurt, Germany” (Appellant’s
August 30, 2019 Appeal Brief (Appeal Br.) 3).
2 Appellant’s January 10, 2020 Reply Brief.
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STATEMENT OF THE CASE
Appellant’s disclosure “relates to the combinations of 1-
aminocyclohexane derivatives and acetylcholinesterase inhibitors and their
use in the treatment of dementia” (Spec.3 1). Appellant’s independent
claims 1 and 7 are reproduced below:
1. A method for providing cognitive improvement in a
subject having severe Alzheimer’s disease, wherein the
cognitive improvement exceeds that which would have been
observed with donepezil monotherapy, the method comprising
administration of a 1-aminocyclohexane derivative selected
from memantine, and salts thereof, and an acetylcholinesterase
inhibitor (AChEI) selected from donepezil, and salts thereof, in
an amount effective for said improvement.
(Appeal Br. 21.)
7. A pharmaceutical composition comprising (i) a 1-
aminocyclohexane derivative selected from memantine and
salts thereof, (ii) an acetylcholinesterase inhibitor (AChEI)
selected from donepezil, and salts thereof, and, optionally, (iii)
a pharmaceutically acceptable carrier or excipient, wherein the
1-aminocyclohexane derivative and acetylcholinesterase
inhibitor (AChEI) are present at therapeutically effective
dosages.
(Id. at 22.)
This Appeal is related to Appeal 2014-009813 (Application
12/661,639) (see Ex parte Moebius, 2017 WL 528039 (PTAB 2017)).
Moebius’ sole independent claim, claim 14, is reproduced below:
14. A method for treating Alzheimer's disease [AD]
comprising administering to a patient in need thereof a
composition for once-a-day administration comprising between
5 and 30 mg of memantine or a pharmaceutically acceptable

3 Appellant’s January 28, 2016 Specification.
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salt thereof and between 5 and 24 mg of donepezil or a
pharmaceutically acceptable salt thereof.
Moebius, 2017 WL 528039 at *1.
In Moebius the rejection of claim 14 under 35 U.S.C. § 103(a) as
unpatentable over, inter alia, the combination of Winblad,4 Feldman,5 and
Wenk,6 was affirmed. Moebius 2017 WL 528039 at *12.

In the present Appeal, we review the rejection of claims 1–11 under
35 U.S.C. § 103(a) as unpatentable over the combination of Winblad,
Feldman, and Wenk.

ISSUE
Does the preponderance of evidence relied upon by Examiner support
a conclusion of obviousness?
FACTUAL FINDINGS (FF)
FF 1. Appellant discloses that “for human administration, both the 1-
aminocyclohexane derivatives[, i.e. memantine,] and AChEIs[, i.e.
donepezil,] are administered in suitable form in doses ranging from about 1
to 200 mg per day for each drug” (Spec. 23; see also Appeal Br. 21
(Appellant’s claim 4 depends from and further limits the amount of AChEI,
i.e. donepezil, in Appellant’s claim 1 to a range of 1 to 200 mg per day)).

4 Winblad et al., Memantine in Severe Dementia: Results of the 9M-Best
Study (Benefit and Efficacy in Severely Demented Patients During
Treatment with Memantine), 14 Int. J. Geriat. Psychiatry 135–46 (1999).
5 Feldman et al., A 24-week, randomized, double-blind study of donepezil in
moderate to severe Alzheimer’s disease, 57 Neurology 613–23 (2001).
6 Wenk et al., No Interaction of Memantine With Acetylcholinesterase
Inhibitors Approved for Clinical Use, 66 Life Sciences 1079–83 (2000).
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FF 2. Winblad discloses “that memantine treatment leads to functional
improvement and reduces care dependence in severely demented patients,”
including patients with Alzheimer’s type dementia (Winblad, Abstract; see
also id. at 144 (Winblad discloses that “memantine treatment significantly
improves functional capacities in severely demented patients and that this
improvement may be considered clinically relevant . . . [and] [t]his equally
holds true for Alzheimer's disease patients”); Ans. 3).
FF 3. Winblad discloses that “patients were randomized to receive either
memantine (5 mg/day during the first week and 10 mg/day during the next
11 weeks) or matching placebo tablets” (Winblad 137; see Ans. 3; cf. FF 1).
FF 4. Examiner finds that Winblad “does not disclose a method further
comprising administering an acetylcholinesterase inhibitor or a
pharmaceutical composition further comprising an acetylcholinesterase
inhibitor” as required by claim 1 in addition to memantine (Ans. 3).
FF 5. Feldman discloses that “[d]onepezil is a reversible and highly
centrally selective inhibitor of acetylcholinesterase (AChE) that has been
shown to significantly improve cognition and maintain patient function in
placebo-controlled trials of 6-month to 1-year duration in mild to moderate
AD” (Feldman 613 (endnotes omitted)).
FF 6. Feldman’s “current study is the first placebo-controlled clinical trial
of donepezil in patients with moderate to severe AD. It was undertaken to
investigate donepezil’s efficacy on global function, cognition, activities of
daily living (ADL), and behavior as well as its safety,” where Feldman
concludes that “donepezil’s benefits extend into more advanced stages of
AD than those previously investigated, with very good tolerability”
(Feldman 613 and Abstract; see Ans. 4).
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FF 7. Feldman discloses that patients were administered donepezil at 5
mg/day for 28 days, then either 5 or 10 mg/day, for a total of 24 weeks (see
Feldman 613–14; Ans. 4; cf. FF 1).
FF 8. Wenk disclosed:
New drug therapies have been designed to either enhance
cholinergic function by inhibiti[ng] acetylcholinesterase
(AChE), e.g. . . . donepezil, or by attenuation of NMDA
receptor function, e.g. memantine. A combination of these two
therapeutic approaches may be more beneficial at slowing the
progression of the AD. The current study investigated whether
memantine would attenuate the inhibition of AChE produced
by these three drugs. The results indicate that these AChE
inhibitors do not lose their therapeutic efficacy in combination
with memantine. Our in vitro data suggest that the clinical
combination of memantine with a reversible AChE inhibitor
should be a valuable pharmacotherapeutic approach to
dementia.
(Wenk 1079; see Ans. 4.)
FF 9. Wenk disclosed “[a] combination of complementary therapeutic
approaches utilizing both memantine and an AChE inhibitor may be more
beneficial at both slowing the progression of the AD, i.e. by providing
neuroprotection from glutamate, as well as enhancing daily cognitive
performance, i.e. by augmenting the function of forebrain cholinergic
neurons” (Wenk 1080;7 see generally Ans. 4).
FF 10. Wenk concluded “that the clinical combination of memantine with a
reversible AChE inhibitor should be valuable pharmacotherapeutic approach

7 Wenk’s Figure 2 supports a finding that because memantine and donepezil
have two distinct mechanisms of action and do not interact with each other,
their combination would have been expected to be a valuable
pharmacotherapeutic approach (see Wenk 1082, Fig. 2; see also Wenk
1082–83).
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to dementia. This combination therapy should result in both neuroprotection
and further functional improvement” (Wenk 1082–83; see generally Ans. 4).
ANALYSIS
Winblad discloses a pharmaceutical composition comprising a
therapeutically effective amount of memantine for use in functionally
improving and reducing “care dependence in severely demented [AD]
patients” (FF 2–3; cf. FF 1). Feldman discloses a pharmaceutical
composition comprising a therapeutically effective amount of donepezil for
the treatment of patients with moderate to severe AD (FF 5–7; cf. FF 1).
The therapeutically effective amounts of memantine and donepezil disclosed
by Winblad and Feldman, respectively, fall within Appellant’s effective
amount of each compound (see FF 2–3 and 5–7; cf. FF 1).
Wenk discloses “that the clinical combination of memantine with a
reversible AChE inhibitor[, such as donepezil,] should be valuable
pharmacotherapeutic approach to dementia. This combination therapy
should result in both neuroprotection and further functional improvement”
(FF 10; see also FF 8–9). Thus, Examiner found that the combination of
Winblad, Feldman, and Wenk makes obvious a pharmaceutical composition
within the scope of Appellant’s claim 7, for use in the treatment of severe
AD (see, e.g., Ans. 4).
It is prima facie obvious to combine two compositions each of
which is taught by the prior art to be useful for the same
purpose, in order to form a third composition which is to be
used for the very same purpose. . . . [T]he idea of combining
them flows logically from their having been individually taught
in the prior art.
In re Kerkhoven, 626 F.2d 846, 850 (CCPA 1980). This is true when
combining two drugs, each known for treating a common disorder, but by
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different mechanisms of action, when the results of the combination would
be predicted in view of the prior art. Novo Nordisk A/S v. Caraco Pharm.
Labs., Ltd., 719 F.3d 1346, 1355-56 (Fed. Cir. 2013) (finding a claim to a
combination of two known diabetes drugs to be obvious).
Therefore, based on the combination of Winblad, Feldman, and
Wenk, we find no error in Examiner’s conclusion that, at the time
Appellant’s claimed invention was made, it would have been prima facie
obvious to a person of ordinary skill in this art
to co-administer memantine and donepezil to a patient suffering
from Alzheimer’s disease, and also to formulate these two
agents into a single pharmaceutical dosage form at a dosage of
10 mg memantine and 5-10 mg donepezil. One of ordinary
skill in the art would have been motivated to do so because the
two agents are seen to be useful for treating the same condition,
namely Alzheimer’s disease. One of ordinary skill in the art
would have reasonably expected success because
Wenk . . . discloses that the two agents can be safely and
effectively co-administered.
(Ans. 4.)
We agree with Appellant’s contention that the method of claim 1
provid[es] cognitive improvement in a subject having severe
Alzheimer’s disease, wherein the cognitive improvement
exceeds that which would have been observed with donepezil
monotherapy, the method comprising administration
of . . . memantine, and . . . donepezil . . . in an amount effective
for said improvement.
(Appeal Br. 7; see generally id. at 5–7; see also Reply Br. 2–5.) As
discussed above, however, the combination of Winblad, Feldman, and Wenk
makes obvious the administration of a composition comprising memantine
and donepezil, in amounts that fall within the scope of Appellant’s claimed
invention, to patients with severe AD (see FF 2–10; cf. FF 1). Specifically,
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each drugs had been used individually to treat Alzheimer’s, and Wenk, as
discussed above, suggested the combination of the two. Thus, even if, as
Appellant contends, the combination of Winblad, Feldman, and Wenk fails
to suggest an improvement in cognition in patients severely affected by
Alzheimer’s disease (see Appeal Br. 8–15), the administration of the
composition suggested by the prior art will, necessarily, achieve the claimed
improvement. See In re Prindle, 297 F.2d 251, 254 (CCPA 1962) (“mere
recognition of . . . latent properties [in the prior art] does not render the
otherwise obvious [invention] unobvious.”); In re Baxter Travenol Labs.,
952 F.2d 388, 392 (Fed. Cir. 1991) (“Mere recognition of latent properties in
the prior art does not render nonobvious an otherwise known invention.”).
We are not persuaded by Appellant’s contention that Winblad
“teaches away from cognitive improvement with memantine” in patients
with severe dementia, because of its disclosure that “cognitive test scores are
clinically less relevant as compared to functional aspects.” (Appeal Br. 8
(citing Winblad 143); see also id. at 16). To the contrary, we find that
Winblad discloses that its focus was on clinically relevant improvements in
the functional rather than on cognitive aspects of its patients. See DePuy
Spine, Inc. v. Medtronic Sofamor Danek, Inc., 567 F.3d 1314, 1327 (Fed.
Cir. 2009) (“A reference does not teach away . . . if it merely expresses a
general preference for an alternative invention but does not ‘criticize,
discredit, or otherwise discourage’ investigation into the invention
claimed.”) (citing In re Fulton, 391 F.3d 1195, 1201 (Fed. Cir. 2004). In
addition, Winblad’s focus on improvement in the functional aspects of its
patients, also does not diminish a finding that Appellant’s recognition of the
latent properties of administering a composition suggested by the
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combination of Winblad, Feldman, and Wenk does not render Appellant’s
obvious invention unobvious. See In re Prindle, 297 F.2d at 254; Ex parte
Obiaya, 227 USPQ at 60.
For the foregoing reasons, we are not persuaded by Appellant’s
contention that Examiner’s rejection is based on improper hindsight (see
Appeal Br. 15).
We recognize Appellant’s reference to “Therapeutic Example 4” of its
Specification (Appeal Br. 18; see Spec. 82–91). Appellant discloses that the
Therapeutic Example 4
study was aimed at evaluating the therapeutic potential in
treatment of AD of a combination therapy comprising
memantine and donepezil. Specifically, the safety and efficacy
of memantine (relative to placebo) was assessed in outpatients
with probable moderate to severe dementia of the Alzheimer’s
type who were also receiving concurrent treatment with a stable
dose of donepezil.
(Spec. 83 (emphasis added); see also id. at 84 (“The study population
consisted of male and female outpatients who were at least 50 years of age.
AD severity ranged from moderate to severe assessed on the basis of Mini
Mental State Examination Scores”) (emphasis added).) We note, however,
that Appellant’s Specification does not separately report results obtained for
the moderate and severe patient populations. Thus, as Examiner explains,
although Appellant’s claimed method provides cognitive improvement in a
subject having severe Alzheimer’s disease, where the cognitive
improvement exceeds that which would have been observed with donepezil
monotherapy, “no actual evidence is provided by [Appellant] proving that
such an effect exists in this [severe AD] patient population” (see Ans. 9).
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Möbius also fails to provide evidence addressing this patient
population (see 2018 Möbius Decl.8). According to Möbius the “treatment
of patients suffering from moderately severe to severe dementia of the
Alzheimer’s type was the focus of . . . [Möbius’] research and the foundation
of [Möbius’] invention memorialized in the instant application” (id. at 3
(emphasis added)). Although Möbius declares that its “development
program was directed toward the treatment of patients suffering from severe
Alzheimer’s disease” and “resulted in truly innovative treatment and, for the
first time, a measurable improvement in cognition in patients severely
affected by Alzheimer’s disease over the standard monotherapy with
Donepezil up to and including the moderate stage only,” the evidence, i.e.
Appellant’s Specification, fails to support the treatment of a patient
population that is limited to providing cognitive improvement in a subject
having severe AD, as claimed (id. 3 and 5 (emphasis added)).
Appellant makes reference to three different patient populations,
specifically those suffering from moderate, moderately severe, or severe
dementia of the Alzheimer’s type. Appellant’s evidence, however, fails to
provide data in support of any specific level of severity. Thus, to the extent
that Appellant would rely upon Therapeutic Example 4 of its Specification,
the 2018 Möbius Decl., or the 2011 Möbius Decl.9 to support an unexpected

8 Dr. med. Hans Jörg Möbius, Declaration under 37 C.F.R. § 1.131, signed
July 14, 2018.
9 Dr. med. Hans Jörg Möbius, Declaration under 37 C.F.R. § 1.131, signed
August 21, 2011. As Examiner explains, the 2011 Möbius Declaration
“includes pages from a notebook maintained by the declarant which includes
the phrase ‘combi mem + donepezil ̶˃ overadditive effects!! Cognition!!’,
which the declarant explains as indicating that they had observed
overadditive effects on cognition of a combination of memantine and
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result, we are not persuaded. In re Dill, 604 F.2d 1356, 1361 (CCPA 1979)
(“The evidence presented to rebut a prima facie case of obviousness must be
commensurate in scope with the claims to which it pertains.”).
CONCLUSION
The preponderance of evidence relied upon by Examiner supports a
conclusion of obviousness.
The rejection of claims 1 and 7 under 35 U.S.C. § 103(a) as
unpatentable over the combination of Winblad, Feldman, and Wenk is
affirmed. Claims 2–6 are not separately argued and fall with claim 1.
Claims 8–11 are not separately argued and fall with claim 7.

DECISION SUMMARY
In summary:
Claims
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
1–11 103(a) Winblad, Feldman,
Wenk
1–11

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

donepezil” (Ans. 10; see also 2011 Möbius Decl. 2 (Möbius declares: “I
recognized the patentability of the memantine (mem) + donepezil
combination” and “considered the overadditive effects with respect to
cognition to be patent eligible”)).