Ex Parte Remick et al

Patent Trial and Appeal Board

Dec 26, 2017

15135580 (P.T.A.B. Dec. 26, 2017)

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.
15/135,580 04/22/2016 David Michael Remick X20656 4306
25885 7590 12/28/2017
FT T T TT T Y fr TOMPANY
EXAMINER
PATENT DIVISION KAROL, JODY LYNN
P.O. BOX 6288
INDIANAPOLIS, IN 46206-6288 ART UNIT PAPER NUMBER
1627
NOTIFICATION DATE DELIVERY MODE
12/28/2017 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):
patents @ lilly.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte DAVID MICHAEL REMICK, SIMON JAMES RICHARDS, and
ADAM JAN SANDERSON
Appeal 2017-009932
Application 15/135,5801
Technology Center 1600
Before ERIC. B. GRIMES, TIMOTHY G. MAJORS, and
DAVID COTTA, Administrative Patent Judges.
COTTA, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving selective
BACE1 inhibitors. Spec. 1. The Examiner rejected the claims on appeal as
obvious under 35 U.S.C. § 103(a).
We reverse.
1 According to Appellants, the real party in interest is Eli Lilly and
Company. App. Br. 1.
Appeal 2017-009932
Application 15/135,580
STATEMENT OF THE CASE
The Specification discloses:
Alzheimer’s disease is characterized by the generation,
aggregation, and deposition of Abeta [(amyloid P)] in the brain.
Complete or partial inhibition of P-secretase (P-site amyloid
precursor protein-cleaving enzyme; BACE) has been shown to
have a significant effect on plaque-related and plaque-
dependent pathologies in mouse models suggesting that even
small reductions in Abeta peptide levels might result in a long­
term significant reduction in plaque burden and synaptic
deficits, thus providing significant therapeutic benefits,
particularly in the treatment of Alzheimer’s disease.
Spec. 1. The Specification asserts that “[t]he present invention provides
certain novel compounds that are inhibitors of BACE” and, more
specifically, that are “selective inhibitors of BACE 1 over BACE2.” Id. at 2.
The Specification discloses that these compounds can be used in a method of
treating Alzheimer’s disease. Id.
Claims 1—3, 7, 8, and 19 are on appeal. Claim 1 is illustrative and
reads as follows:
1. A compound of the formula:
F
S
F
NH2
or a pharmaceutically acceptable salt thereof.
App. Br. 13.
2
Appeal 2017-009932
Application 15/135,580
The Examiner rejected claims 1—3, 7, 8, and 19 under 35 U.S.C.
§ 103(a) as obvious over Suzuki.2
ANALYSIS
In finding the pending claims obvious, the Examiner found that
Suzuki disclosed compounds that inhibit production of Ap or BACE1 and
are useful as prophylactic or therapeutic agents for treatment of
neurodegenerative disease caused by Ap, as typified by Alzheimer-type
dementia. Final Act.3 6. The Examiner further found that Example 280 of
Suzuki disclosed the synthesis of N-[3-((4aS,5S,7aS)-2-amino-5-
difluoromethyl-4a,5,7,7a-tetrahydro-4H-furo[3,4-d] [ 1,3]thiazin-7a-yl)-4-
fluorophenyl]-5-dihydropyridine-2-carboxamide. Id.
The compound of Example 280 differs from the claimed compound in
that the claimed compound contains a methyl group substituted for the
hydrogen in the difluoromethyl group as reflected in the below comparison.
difluoromethyl group
1,1*difiuQro-1-efhyi group
/ \
| F h!
F-O/ H
position 5 n\~"7Ny
$
A
..-A'
H H
F-V «
v-h
Compound 280 Elected Species
from Suzuki ot aL Example 1
The above figure was included by Appellants in the Appeal Brief and
provides a comparison of the compound of Example 280 of Suzuki to the
compound disclosed in Example 1 of the Specification. App. Br. 9.
2 Suzuki et al., US Patent No. 8,158,620 B2, issued Apr. 17, 2012
(“Suzuki”).
3 Office Action mailed February 9, 2017 (“Final Act.”).
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Appeal 2017-009932
Application 15/135,580
Based on the disclosure of compound 280, the Examiner concluded
that “[i]t would have been obvious to one of ordinary skill in the art prior to
the filing date of the invention to substitute the hydrogen of Compound 280
taught by Suzuki et al. with a methyl group to arrive at the instantly claimed
compound.” Final Act. 7. The Examiner reasoned that “[i]t is well
established that the substitution of methyl for hydrogen on a known
compound is not a patentable modification absent unexpected or unobvious
results.” Id. (citing case law). The Examiner further reasoned that “the
compounds of Suzuki et al. and the elected species of the instant invention
would have been expected to have similar properties based on close
structural and chemical similarity and the fact that both the prior art and the
applicant used the compounds as BACE1 inhibitors.” Id. at 7—8,
Appellants contend that Suzuki discloses a genus covering trillions of
compounds and exemplifies 286 compounds falling within this genus. App.
Br. 5. Appellants argue, inter alia, that neither the Examiner nor Suzuki
provides reason to select compound 280 from among this large genus of
compounds. Id. Appellants note that Suzuki provides IC50 data for 176 of
the 286 exemplified compounds, but not for compound 280. Id. Appellants
further note that Suzuki does not does not identify compound 280 as a
preferred compound, highlight compound 280, or otherwise indicate that
compound 280 provides any “benefit or special property” as compared to
any of the other compounds disclosed. Id. Finally, Appellants note that no
biological data is provided for compound 280. Id. Appellants thus assert
that “one of ordinary skill in the art would have no reason to identify
Compound 280 as a natural choice for further development efforts, and thus,
a lead compound.” Id.
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Appeal 2017-009932
Application 15/135,580
As stated in In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992):
“[T]he examiner bears the initial burden ... of presenting a prima facie case
of unpatentability.” Appellants have persuaded us that the Examiner has not
carried the burden of establishing that the claimed invention would have
been obvious over the cited art.
The Examiner relied on a lead compound analysis to find the claimed
compound obvious. Final Act. 6—8; Ans. 6—10. A lead compound is defined
as ‘“a compound in the prior art that would be most promising to modify in
order to improve upon its . . . activity and obtain a compound with better
activity.’” Otsuka Pharm. Co., Ltd. v. Sandoz, Inc., 678 F.3d 1280, 1291
(Fed. Cir. 2012) (citing Takeda Chem. Indus., Ltd. v. Alphapharm Pty., Ltd.,
492 F.3d 1350, 1357 (Fed. Cir. 2007)). Stated another way, “a lead
compound is ‘a natural choice for further development efforts.’” Id. (citing
Altana Pharma AG v. Teva Pharm. USA, Inc., 566 F.3d 999, 1008 (Fed. Cir.
2009)). “While the lead compound analysis must, in keeping with KSR, not
rigidly focus on the selection of a single, best lead compound,... the
analysis still requires the challenger to demonstrate . . . that one of ordinary
skill in the art would have had a reason to select a proposed lead compound
or compounds over other compounds in the prior art.” Daiichi Sankyo Co.,
Ltd. v. Matrix Laboratories, Ltd., 619 F.3d 1346, 1354 (Fed. Cir. 2010).
The analysis of whether a person of ordinary skill would have chosen the
prior art compound as a lead compound “is guided by evidence of the
compound’s pertinent properties” including “positive attributes such as
activity and potency,” “adverse effects such as toxicity,” “and other relevant
characteristics in evidence.” Otsuka, 678 F.3d at 1292.
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Appeal 2017-009932
Application 15/135,580
Importantly, “[ajbsent a reason or motivation based on such prior art
evidence, mere structural similarity between a prior art compound and the
claimed compound does not inform the lead compound selection.” Id.', see
also Daiichi, 619 F.3d at 1354 (“[Pjroving a reason to select a compound as
a lead compound depends on more than just structural similarity, but also
knowledge in the art of the functional properties and limitations of the prior
art compounds.”).
Suzuki discloses a genus of Ap and BACE1 inhibitory compounds
encompassing, according to Appellants, trillions of compounds. App. Br. 5.
Suzuki exemplifies 286 compounds falling within this broad genus. See,
Suzuki col. 56,1. 5 — col. 428,1. 10. The Examiner, however, does not
identity any teaching in the prior art that would have directed the skilled
artisan to select compound 280 from among the many compounds disclosed
and exemplified in Suzuki. Under Daiichi it is possible to have multiple
lead compounds, but even considering only the compounds exemplified in
Suzuki, it would not be reasonable to classify all 286 compounds as joint
lead compounds. We are therefore persuaded by Appellants that the
Examiner has not shown that a skilled artisan would have been led to treat
compound 280 as a lead compound that would have been obvious to modify.
Accordingly we reverse the Examiner’s rejection of claims 1—3, 7, 8, and 19
as obvious over Suzuki.
DECISION
For the reasons set forth herein, we reverse the Examiner’s rejection
of claims 1—3, 7, 8, and 19 under 35 U.S.C. § 103(a) as obvious over Suzuki.
REVERSED
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