Ex Parte Friedl et al

Patent Trial and Appeal Board

Jun 11, 2013

10965994 (P.T.A.B. Jun. 11, 2013)

UNITED STATES PATENT AND TRADEMARK OFFICE
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BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte THOMAS FRIEDL, JOACHIM MIERAU,
ANDREAS RASCHIG, JUERGEN REESS, and
JOERGEN SCHEEL-KRUEGER
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Appeal 2012-012227
Application 10/965,994
Technology Center 1600
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Before TONI R. SCHEINER, DONALD E. ADAMS, and FRANCISCO C.
PRATS, Administrative Patent Judges.

ADAMS, Administrative Patent Judge.

DECISION ON APPEAL1,2
This appeal under 35 U.S.C. § 134 involves claims 1, 12, 19, and 22-24
(App. Br. 3; Reply Br. 2; Ans. 3).3 Examiner entered rejections under 35
U.S.C. § 103(a). We have jurisdiction under 35 U.S.C. § 6(b).
We affirm.

1 The Real Party in Interest is NEUROSEARCH A/S (App. Br. 1).
2 This Appeal is related to Appeal 2008-3908, Application 10/965,994,
Opinion Affirming Examiner entered December 22, 2008. See http://e-
foia.uspto.gov/Foia/ReterivePdf?system=BPAI&flNm=fd20083908-12-22-
2008-1.
3 Pending claims 15-18 stand withdrawn from consideration (App. Br. 3).
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STATEMENT OF THE CASE
The claims are directed to a composition (claims 1, 12, 22, and 24)
and a pharmaceutical kit (claims 19 and 23). Claim 1 is representative and is
reproduced in the Claims Appendix of Appellants’ Brief.
Claims 1, 12, 19, and 22-24 stand rejected under 35 U.S.C. § 103(a)
as unpatentable over the combination of Scheel-Krüger4 and Simonson.5
ISSUE
Does the preponderance of evidence relied upon by Examiner support
a conclusion of obviousness?
FACTUAL FINDINGS (FF)
FF 1. Scheel-Krüger suggests “tropane derivatives, [such as (1R, 2R, 3S)-
2-ethoxymethyl-3-(3,4-dichlorophenyl)-tropane),] which are valuable
monoamine neurotransmitter (dopamine, serotonin, and noradrenaline)
reuptake inhibitors for the treatment of … Alzheimer’s disease” (Ans. 5; see
also Spec. 12: 13-14 and 13: 20 (the tropane derivative may be (1R, 2R, 3S)-
2-ethoxymethyl-3-(3,4-dichlorophenyl)-tropane)); Reply Br. 7).
FF 2. Scheel-Krüger suggests that “the dosage range for the active
ingredient ... [is] between 0.1 to 100 mg” (Ans . 5).
FF 3. Scheel-Krüger suggests “compositions comprising … tropane
derivatives … [in combination with] other therapeutic ingredients” (id.).
FF 4. Scheel-Krüger “fails to disclose the acetylcholinesterase inhibitor,
donepezil” (id.).
FF 5. Simonson suggests “acetycholinesterase inhibitors[, such as
donepezil,] for the treatment of Alzheimer’s disease” (id.).

4 Scheel-Krüger et al., WO 97/30997, published August 28, 1997.
5 William Simonson, “Promising agents for treating Alzheimer’s disease,”
55 (SUPPL. 2) AM. J. HEALTH SYST. PHARM., S11-S16 (1998).
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FF 6. Simonson suggests an acetylcholinesterase inhibitor dosage of “from
5 to 10 mg” (id.).
FF 7. Simonson suggests the combination of acetycholinesterase inhibitors
with other drugs that “address symptoms that probably occur because of
deficits in serotonergic, noradrenergic, or dopaminergic function. A ChEI
[(cholinesterase inhibitor)] plus a selective serotonin-reuptake inhibitor, for
example, may improve cognition and reduce symptoms of depression”
(Simonson S15: col. 1, ll. 8-13; see also Ans. 6).
FF 8. Meier states that the combination of tesofensine and donepezil “did
not entail safety concerns compared with the single use of either drug” and
“[t]he MMSE revealed minor improvements in all groups [(a) tesofensine
given as add-on to 10 mg donepezil once daily over 14 weeks and (b)
placebo, which is reported as donepezil alone] at the end of the treatment”
(First Meier Declaration6 2-3: ¶ 9A and 3: ¶9C; see also Hyveld-Nielsen
Declaration7 2: 20-23).
FF 9. Meier states that as of the date of the Second Meier Declaration8
“[t]he state of the art pertaining to drugs that combine[] two or more active
ingredients for use in treating neurodegenerative diseases such as
Alzheimer’s Disease is unpredictable” (Second Meier Declaration 3: ¶ 10;
Hyveld-Nielsen Declaration 5: 20).
FF 10. Meir states that “not all drug combinations will provide greater
benefits than those achieved with each drug alone” (Second Meier
Declaration 4: ¶ 10, quoting Simonson S15 (emphasis added)).

6 First Declaration of Dieter H. Meier, executed of April 16, 2010.
7 Declaration of Lars Hyveled-Nielsen, executed October 3, 2011.
8 Second Declaration of Dieter H. Meier, executed April 16, 2010.
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FF 11. Meier states that “[t]here is no particular direction … to use a drug
disclosed in a reference like Scheel-Krüger to treat neurodegenerative
diseases such as Alzheimer’s Disease” (Second Meier Declaration 5: ¶ 12).
FF 12. Fox, a literature review, assesses the available data on the use of a
combination memantine-cholinesterase inhibitor (ChEI) therapy for
Alzheimer’s disease, and concludes that “the use of memantine-ChEI
combination therapy cannot be recommended as there is no evidence that
combination therapy is more effective than memantine monotherapy” (Fox9
121: Abstract; 124: col. 1, ll. 10-13).
FF 13. Atri provides the results of a clinical trial “[t]o compare the real-
world clinical effectiveness and long-term clinical trajectory in patients with
Alzheimer’s disease … treated with combination … therapy consisting of
cholinesterase-inhibitor (CI) plus memantine (MEM) versus CI alone versus
no treatment with either” and concludes that “[c]ombination therapy slows
congnitive and functional decline in AD compare to CI-monotherapy and no
treatment” (Atri10 209: Abstract).
ANALYSIS
Simonson suggests the administration of 5-10 mg of donepezil, a
acetylcholinesterase inhibitor in combination with a monoamine oxidase
inhibitor, such as a serotonergic or dopamerinergic reuptake inhibitor, for
the treatment of Alzheimer’s disease (FF 5-7). Scheel-Krüger suggests the

9 Chris Fox, et al., Memantine combined with an acetyl cholinesterase
inhibitor – hope for the future?, 2(2) NEUROPSYCHIATRIC DISEASE AND
TREATMENT 121-125 (2006).
10 Alireza Atri, et al., Long-term Course and Effectiveness of Combination
Therapy in Alzheimer’s Disease, 22(3) ALZHEIMER DIS. ASSOC. DISORD.
209-221 (2008).
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administration of 0.1-100 mg of the monoamine dopamine or serotonin
neurotransmitter reuptake inhibitor (1R, 2R, 3S)-2-ethoxymethyl-3-(3,4-
dichlorophenyl)-tropane), in combination with other therapeutic ingredients,
for the treatment of Alzheimer’s disease (FF 1-3; see also Ans. 12). Based
on the combination of Scheel-Krüger and Simonson, Examiner concludes
that, at the time Appellants’ invention was made, it would have been prima
facie obvious “to combine … [ (1R, 2R, 3S)-2-ethoxymethyl-3-(3,4-
dichlorophenyl)-tropane) as suggested] by Scheel-Krüger … with the
acetylcholinesterase inhibitor, donepezil, taught by Simonson” to treat
Alzheimer’s Disease (Ans. 6).
Simonson suggests the combination of donepezil and a monoamine
dopamine or serotonin neurotransmitter reuptake inhibitor, such as (1R, 2R,
3S)-2-ethoxymethyl-3-(3,4-dichlorophenyl)-tropane); therefore, we are not
persuaded by Appellants’ contention
that the tropane compound for use according to …
[Appellants’] invention is one out of 13 different compounds
identified in the Scheel-Krüger reference, and that the medical
indication (dementia of the Alzheimer type (‘DAT’))
contemplated according to … [Appellants’] invention is one out
of about 11 diseases/disorder also proposed in Scheel-Krüger.
(App. Br. 17; see also id. at 18 (“just because the prior art teaches that an
individual drug can be used to treat a specific disease does not mean a
claimed combination of drugs is predictable”); FF 11.) For the same reason
we are not persuaded by Appellants’ contention that “finding a suitable drug
to treat Alzheimer’s disease is not predictable, and if anything, is very
unpredictable” (App. Br. 17; see also FF 9).
We recognize, but are not persuaded by, Appellants’ contentions
regarding the BI Trial Nos.: 1198.52 and 1198.22 suggesting that the
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combination of (1R, 2R, 3S)-2-ethoxymethyl-3-(3,4-dichlorophenyl)-
tropane) and donepezil was more efficacious for the treatment of
Alzheimer’s Disease than treatment with (1R, 2R, 3S)-2-ethoxymethyl-3-
(3,4-dichlorophenyl)-tropane) alone (App. Br. 17-18; Reply Br. 10-12; see
also Hyveld-Nielsen Declaration Attachments; FF 10). Notwithstanding
Appellants’ intimation to the contrary, the evidence on this record does more
than provide “general guidance as to the particular form of the claimed
invention or how to achieve it.” See In re Kubin, 561 F.3d 1351, 1359 (Fed.
Cir. 2009) (quoting In re O'Farrell, 853 F.2d 894, 903 (Fed. Cir. 1988)).
The evidence relied upon by Examiner suggests the treatment of
Alzheimer’s Disease with a composition comprising the combination of (a)
donepezil and (b) a monoamine dopamine or serotonin neurotransmitter
reuptake inhibitor, such as (1R, 2R, 3S)-2-ethoxymethyl-3-(3,4-
dichlorophenyl)-tropane), at dosage ranges that fall within (donepezil) or
overlap ((1R, 2R, 3S)-2-ethoxymethyl-3-(3,4-dichlorophenyl)-tropane) those
required by Appellants’ claimed invention (FF 1-3 and 5-7). Therefore, the
evidence on this record fails to support a conclusion that the results obtained
through the use of Appellants’ claimed composition is more than a
“predictable use of known prior art elements.” KSR Int’l Co. v. Teleflex Inc.,
550 U.S. 398, 417 (2007); Cf. FF 8-11; App. Br. 23 (“Simonson provides a
catalogue of entirely speculative approaches, and is far from being a road to
success”). Section 103 bars patentability unless “the improvement is more
than the predictable use of prior art elements according to their established
functions.” Id. While Appellants correctly note that Simonson suggests that
“not all drug combinations will provide greater benefits than those achieved
with each drug alone,” the combination of Scheel-Krüger and Simonson
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suggest the composition of Appellants’ claim 1 (see Reply Br. 9-10; FF 10;
Cf. FF 1-3 and 5-7; see also Ans. 11 (“The reference to … Simonson is not
persuasive because it is drawn to the combination of selegiline-vitamin E,
and not to the claimed combination of the 2,3-disubstituted tropane moiety
of formula IA and the acetylcholinesterase inhibitor, donepezil”)).
For the foregoing reasons we are not persuaded by Appellants’
contention that “Donepezil … works completely differently from the
claimed compound (1)[, which is a 2,3-disubstituted tropane moiety, such as
(1R, 2R, 3S)-2-ethoxymethyl-3-(3,4-dichlorophenyl)-tropane),] and thus
there is no reasonable expectation of success in producing the instantly
claimed composition comprising a tropane derivative and an
acetylcholinesterase inhibitor” (App. Br. 24). Notwithstanding Appellants’
contention that the two components of the claims composition exhibit
different modes of action, the prior art relied upon by Examiner suggests a
composition comprising the claimed components for the treatment of
Alzheimer’s Disease (FF 1-3 and 5-7).
As discussed above, the prior art relied upon by Examiner suggests a
composition comprising dosage ranges that fall within (donepezil) or overlap
((1R, 2R, 3S)-2-ethoxymethyl-3-(3,4-dichlorophenyl)-tropane) those
required by Appellants’ claimed invention (FF 2 and 6). Therefore, we are
not persuaded by Appellants’ contention that “[t]he present invention allows
for the use of each compound in lower doses than those used in a
monotherapy, with a concomitant reduction of side effects” (App. Br. 19).
“[W]here there is a range disclosed in the prior art, and the claimed
invention falls within that range, there is a presumption of obviousness.”
Iron Grip Barbell Co. v. USA Sports, Inc., 392 F.3d 1317, 1322 (Fed. Cir.
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2004). In this regard, a person of ordinary skill in this art would reasonably
expect that lower therapeutic dosages would result in a reduction of side
effects (see Ans. 9; Cf. App. Br. 19).
We recognize, but are not persuaded by Appellants’ contentions
relating to Fox and Atri, which address a combination therapy that differs
from the combination suggested by the combination of Scheel-Krüger and
Simonson (see App. Br. 20-21; see also Reply Br. 9; FF 12-13; Cf. FF 1-7;
Ans. 11).
We recognize, but are not persuaded by Appellants’ contention that
((1R, 2R, 3S)-2-ethoxymethyl-3-(3,4-dichlorophenyl)-tropane) is not
suggested by Simonson because “the only type of reuptake inhibitor
proposed by Simonson is a selective serotonin reuptake inhibitor” (Reply Br.
8). While Simonson exemplified a selective serotonin reuptake inhibitor,
Simonson more generally suggests the combination of acetycholinesterase
inhibitors with drugs that address deficits in serotongergic, and
dopaminergic function such as the reuptake inhibitor ((1R, 2R, 3S)-2-
ethoxymethyl-3-(3,4-dichlorophenyl)-tropane) suggested by Scheel-Krüger
(FF 7; see also FF 1).
CONCLUSION OF LAW
The preponderance of evidence relied upon by Examiner supports a
conclusion of obviousness. The rejection of claim 1 under 35 U.S.C.
§ 103(a) as unpatentable over the combination of Scheel-Krüger and
Simonson is affirmed. Claims 12, 19, and 22-24 are not separately argued
and fall with claim 1.

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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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