DSM IP ASSETS B.V.

Patent Trials and Appeals Board

Aug 27, 2020

15697723 - (D) (P.T.A.B. Aug. 27, 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.
15/697,723 09/07/2017 Werner BONRATH BHD-4662-3503 4600
23117 7590 08/27/2020
NIXON & VANDERHYE, PC
901 NORTH GLEBE ROAD, 11TH FLOOR
ARLINGTON, VA 22203
EXAMINER
PATEL, SAGAR S
ART UNIT PAPER NUMBER
1626
NOTIFICATION DATE DELIVERY MODE
08/27/2020 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):
PTOMAIL@nixonvan.com
pair_nixon@firsttofile.com
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte WERNER BONRATH, KUN PENG,
LEI ZHANG, and ZHIBIN ZHU

Appeal 2019-006507
Application 15/697,723
Technology Center 1600
____________

Before RICHARD M. LEBOVITZ, ULRIKE W. JENKS, and
TAWEN CHANG, Administrative Patent Judges.

JENKS, Administrative Patent Judge.

DECISION ON APPEAL
Pursuant to 35 U.S.C. § 134(a), Appellant1 files this appeal from
Examiner’s decision to reject claims as obvious. We have jurisdiction under
35 U.S.C. § 6(b).
We AFFIRM.

1 Appellant identifies the real party in interest as DSM IP Assets, BV. Br. 2.
We use the word “Appellant” to refer to “applicant” as defined in 37 C.F.R.
§ 1.42(a).
Appeal 2019-006507
Application 15/697,723
2
STATEMENT OF THE CASE
Claims 1–10 are on appeal, and can be found in the Claims Appendix
of the Appeal Brief. Claim 1, is representative of the claims on appeal, and
reads as follows:
1. A process for the preparation of a substituted
imidazothiazolone compound of formula (I), or a stereoisomer
thereof, or a stereoisomeric mixture thereof, which comprises:
reacting a compound of formula (II), or a stereoisomer thereof,
or a stereoisomeric mixture thereof, with a nucleophile in the
presence of a fluoride-free Lewis acid to provide the compound
of formula (I), or a stereoisomer thereof, or a stereoisomeric
mixture thereof:

wherein R is H, alkyl or alkylcarbonyl; R1 is benzyl; and R2 is
alkyl group.
Br. 14 (Claims Appendix).
REJECTION
Appellant requests review of Examiner’s rejection under 35 U.S.C.
§ 103 of claims 1–10 as obvious in view of US ’3282 and Schmitt.3

2 Chavan et al., US 6,486,328 B1, issued Nov. 26, 2002 (“US ’328”).
3 Schmitt and Reissig, Lewis Acid-Promoted Reactions of y-Lactols with
Silyl Enol Ethers – Stereoselective Formation of Functionalized
Tetrahydrofuran Derivatives, Eur. J. Org. Chem. 1169–74 (2001)
(“Schmitt”).
Appeal 2019-006507
Application 15/697,723
3
OBVIOUSNESS OVER US ’328 AND SCHMITT
The issue in this rejection is whether the preponderance of evidence of
record supports Examiner’s conclusion that the use of a fluoride-free Lewis
acid is obvious in a reaction set out in US ’328, which uses silyl enol ether
as a nucleophile.
A. Findings of Fact (FF)
FF1. Example 5 of US ’328 teaches the production of 6-Benzyl-7-(1-
trimethylsilyloxy-2-oxocyclohexyl)-3-phenyl-(3S, 7R, 7aR)-
perhydroimidazo[1,5-C][1,3]thiazole-5-one. US ’328, 6:30–57. The
starting reactant was mixed with dichlorormethane and 1,2-
bistrimethylsilyloxy cyclohexene, the Lewis acid boron trifluoride
etherate (BF3Et2O) was added, and the reaction was stirred for 10 min
at 0°C. Id. The product yield was 22%. Id. at 6:54.
FF2. Examiner finds that the chemical compounds in the reaction
described in Example 5 of US ’328 have the following
structures:

The figure shows the chemical structures of the reactants in US ’328
Example 5. Ans. 4. Examiner finds that the product of the reaction
depicted above is encompassed by the claimed structure, wherein R is
H, R1 is benzyl, and R2 is l-hydroxyl-2-oxocyclohexyl. Id. at 5.
Appeal 2019-006507
Application 15/697,723
4
FF3. Example 6 of US ’328 teaches the production of 6-Benzyl-7-(1-
trimethylsilyloxy-2-oxocyclohexyl)-3-phenyl-(3S, 7R, 7aR)-
perhydroimidazo[1,5-C][1,3]thiazole-5-one. US ’328 6:60–
7:11. This is the same compound produced in Example 5. The
starting reactant was mixed with dichlorormethane and 1,2-
bistrimethylsilyloxy cyclohexene, followed by adding the
Lewis acid boron trifluoride etherate (BF3Et2O), and then the
reaction was stirred for 10 min at 10°C. Id. The product yield
was 98%. Id. at 7:11.
FF4. Schmitt teaches a Lewis acid promoted reaction with γ-lactols.
Schmitt, Abstract. The phenyl-substituted γ-lactol gives a fairly
high trans-selective reaction with silyl enol ether in the
presence of zinc chloride as shown below in scheme 3:

The figure above shows the chemical structures involved in the
reaction of the phenyl-substituted γ-lactol (1b) with silyl enol ether in
the presence of the Lewis acid ZnCl2. Schmitt 1170.
The transformation of the silyl enol ether into substitution
product using two different Lewis acids is shown below as scheme 4:
Appeal 2019-006507
Application 15/697,723
5

The figure above shows the chemical structures involved in the
reaction of a γ-lactol (1c) with silyl enol ether in the presence of the
Lewis acid ZnCl2 or BF3Et2O. Id. Scheme 4 shows that “the
diastereoselectivity of the γ-lactol reactions is independent of the
Lewis acid employed. With BF3Et2O and with ZnC12 almost identical
trans:cis ratios were observed, but the milder zinc Lewis acid [ZnCl2
with a product yield of 61%] afforded a considerably higher yield.”
Id.
B. Analysis
Examiner finds that US ’328 teaches the preparation of a substituted
imidazothiazolone compound of formula (I) of claim 1. Ans. 4; FF1–FF3.
Examiner acknowledges that in US ’328 the reaction occurs “in the presence
Appeal 2019-006507
Application 15/697,723
6
of [fluoride containing] Lewis acid, Boron trifluoride etherate, and the
organic solvent, Dichloromethane.” Ans. 4; FF1–FF3. Examiner
acknowledges that US ’328 does not disclose using a fluoride-free Lewis
acid and achieving selectivity greater than 83% and higher as recited in
claims 9 and 10, which depend from claim 1. Ans. 6.
Examiner looks to Schmitt for teaching that “zinc chloride is the most
suitable Lewis acid over boron trifluoride etherate and diethylaluminium
chloride, when silyl enol ethers are employed as nucleophiles for the
treatment of γ-lactols.” Ans. 8 (emphasis removed); FF4.
Based on the combined teaching of US ’328 and Schmitt, Examiner
concludes that
it would have been obvious to a person having ordinary skill in
the art at the time the invention was filed to perform routine
experimentation and incorporate the teachings of zinc chlorides
[with silyl enol ethers as nucleophiles] as set forth by Schmitt
with the process of using silyl enol ethers as nucleophiles as set
forth by US ’328 in order to enhance the preparation method
and increase the product yield of substituted imidazothiazolone
compounds, with a reasonable expectation of success.
Ans. 8.
Upon consideration of the evidence on this record, and each of
Appellant’s contentions, we find that the preponderance of evidence
supports the Examiner’s conclusion that the subject matter of Appellant’s
claims is unpatentable. Accordingly, we affirm Examiner’s rejections for the
reasons set forth in the Answer and Final Action. We address Appellant’s
contentions below.
Appellant contends that there is a lack of reasonable expectation of
success because the starting molecule acted on by the Lewis acid in US ’338
and Schmitt are structurally different. Br. 9. Appellant contends:
Appeal 2019-006507
Application 15/697,723
7
Firstly, the compound of formula (II) employed in the process
of the herein claimed invention [and disclosed in US ’328] is an
imidazothiazolone compound having two rings whereas the γ-
lactols employed in the process of the Schmitt et al publication
have only one ring. Secondly, it will be observed that the
compound of formula (II) employed in the process of the herein
claimed invention has three heteroatoms, i.e., one oxygen atom
(0) and two nitrogen atoms (N), while the γ-lactols employed in
the process of the Schmitt et al publication have only one
heteroatom (O).
Br. 8.
We are not persuaded by Appellant’s contention that the starting
molecules in US ’328 and Schmitt are structurally so different that a skilled
artisan would not have expected a silyl enol ether as a nucleophile in
conjunction with a Lewis acid to react with the different starting molecules
to produce the substituted product. Specifically, Appellant’s argument that
because of the “substantial structural differences, a person ordinarily skilled
in the art could not reasonably predict the success of the Lewis acid
BF3•Et2O and ZnCl2 in the reaction of the compound of formula (II)” is
unsupported attorney argument and, therefore, unpersuasive. See In re De
Blauwe, 736 F.2d 699, 705 (Fed. Cir. 1984) (explaining that arguments and
conclusions unsupported by factual evidence carry no evidentiary weight).
As Examiner explains, “the process of using fluoride-free Lewis acids
with silyl enol ethers as nucleophiles is/would have been a commonly
known technique to a person skilled in the art.” Ans. 11; FF4. We agree that
the record supports Examiner’s position that when using silyl enol ethers as
nucleophiles in conjunction with a Lewis acid in a reaction, the fluoride
based (BF3Et2O) or fluoride-free (ZnCl2) Lewis acids are interchangeable as
specifically taught by Schmitt. See FF4. Appellant did not provide objective
Appeal 2019-006507
Application 15/697,723
8
evidence that it would have been unpredictable that Schmitt’s Lewis acid
would work in the reaction described in US ’328, particularly when the
underlying nucleophile chemistry is the same in both reactions. Furthermore,
“[o]bviousness does not require absolute predictability of success. . . . For
obviousness under § 103, all that is required is a reasonable expectation of
success.” In re O’Farrell, 853 F.2d 894, 903-04 (Fed. Cir. 1988).
Appellant contends that it was surprising to achieve such high yield in
the presence of fluoride-free Lewis acid. Br. 12 (The method “provides
unexpectedly higher yield4 of the compound of formula (I) as compared to
the processes as disclosed in US ’328 and Schmitt et al. For example, when
the Lewis acid ZnCl2 is used, the yield is 91 % of the compound 3.”).
We agree with Examiner that Appellant’s contentions with respect to
high yield is not persuasive. As Examiner explains, in US ’328 examples 5
and 6 disclose the production of compound of formula (I). See Ans. 12; FF1,
FF3. The same compound is produced in both examples. While the reactants
are the same, the reaction temperature is different between these two
examples. Compare FF1 with FF3. As Examiner points out example 6 has
product yield of 98%. Ans.12. This increase in product yield is achieved by
raising the reaction condition by 10°C. FF1. Compare FF1 with FF3. In
addition, Examiner explains that “Schmitt teaches that ZnCl2 afforded a
considerably higher yield as a Lewis acid over boron trifluoride etherate,
BF3•Et2O, and diethylaluminium chloride.” Ans. 12; FF4. Schmitt shows

4 Appellant argues “high yield,” which is different from “high selectivity.”
See Spec. 6, table 1. Based on the disclosure in the Specification, we
interpret “high yield” to be the amount of product (formula (I)) made as
opposed to any by-product.
Appeal 2019-006507
Application 15/697,723
9
that the product yield using BF3•Et2O is 20% while substituting ZnCl2 in the
same reaction results in a product yield of 61%. FF4. Based on the
advantages of ZnCl2 as a Lewis acid as taught in Schmitt we agree with
Examiner that that there is ample motivation to substitute ZnCl2 as the Lewis
acid in the reaction as taught in US ’328 with an expectation of achieving a
high yield. Examiner’s position is that through performing routine
experimentation there would have been a reasonable expectation to achieve
higher product yields. See Ans. 12. We agree that the record supports the
position that changing either the temperature of the reaction or the Lewis
acid are ways to increase product yield. FF1, FF3, FF4. Picking one of a
finite number of known solutions to a known problem is obvious. KSR Int’l
Co. v. Teleflex Inc., 550 U.S. 398, 421 (2007).
For the foregoing reasons we affirm Examiner’s obviousness
rejections.
C. Conclusion
We conclude that the evidence cited by Examiner supports a prima
facie case of obviousness with respect to claim 1, and Appellant has not
provided persuasive evidence to rebut the prima facie case. As Appellant
does not argue the claims separately, claims 2–10 fall with claim 1.
37 C.F.R. § 41.37 (c)(1)(iv).

Appeal 2019-006507
Application 15/697,723
10
DECISION SUMMARY
In summary:
Claims
Rejected
35 U.S.C.
§
Reference(s)/Basis Affirmed Reversed
1–10 103 US ’328, Schmitt 1–10

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