Ex Parte Schiffers et al

Patent Trial and Appeal Board

Sep 24, 2013

11060510 (P.T.A.B. Sep. 24, 2013)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte ROBERT SCHIFFERS, PAUL KREYE,
WOLFGANG BAUMGARTEN, and ROSEMARIE COLLET
__________

Appeal 2012-003855
Application 11/060,510
Technology Center 1600
__________

Before DONALD E. ADAMS, DEMETRA J. MILLS, and
LORA M. GREEN, Administrative Patent Judges.

MILLS, Administrative Patent Judge.

DECISION ON APPEAL

This is an appeal under 35 U.S.C. § 134. The Examiner has rejected
the claims for obviousness. We have jurisdiction under 35 U.S.C. § 6(b).
Appeal 2012-003855
Application 11/060,510

2
STATEMENT OF CASE
Claim 1 is representative.

1. A process for preparing chiral N-alkyl-N-methyl-3-hydroxy-3-(2-thienyl)-
propylamine of formula I,

wherein Rl denotes a –Cl-6-alkyl group optionally substituted by phenyl, or
an acid addition salt thereof, starting from prochiral 1-(N-alkyl-N-
methylamino)-3-(2-thienyl)propan-3-one of formula II,

wherein R1 is as hereinbefore defined, or an acid addition salt thereof,
comprising subjecting the compound of formula II to asymmetric
hydrogenation in the presence of a catalyst system consisting of rhodium,
(2R, 4R)-4-(dicyclohexylphosphino )-2-(diphenylphosphino-methyl)-N-
methyl-aminocarbonyl-pyrrolidine and, optionally, an inert diluent and a
weak base.

Cited References

Jack Deeter et al., Asymmetric Synthesis and Absolute Stereochemistry of
LY248686, 31 TETRAHEDRON LETTERS, NO. 49, 7101-7104 (1990).
Appeal 2012-003855
Application 11/060,510

3
Shunji Sakuraba et al., Efficient Asymmetric Hydrogenation of β- and y-
Amino Ketone Derivatives Leading to Practical Synthesis of Fluoxetine and
Eprozinol, 43 CHEM PHARM. BULL., NO. 5, 748-753 (1995).

Bernard G. Van den Hoven et al., The First Regioselective Hydroformylation
of Acetylenic Thiophenes Catalyzed by a Zwitterionic Rhodium Complex and
Triphenyl Phosphite, 64 J. ORG. CHEM., 9640-9645 (1999).

Appellants’ evidence

L. Vradman et al. Regeneration of Poisoned Nickel Catalyst by Supercritical
CO2 Extraction, 40 IND. ENG. CHEM. RES., 1589-90 (2001).

A. J. Birch et al. Homogeneous Hydrogenation in the Presence of Sulphur
Compounds, 20 TETRAHEDRON LETTERS, 1935-36 (1967).

P. Reyes et al., RESISTANCE TO SULFUR POISONING OF Rh
SUPPORTED CATALYSTS, 67 REACT. KINET, CATAL. LETT., NO. 1, 177-182
(1999).

Rabinovich et al., US 4,399,051, Aug. 16, 1983.

Grounds of Rejection
Claims 1-30 rejected under 35 U.S.C. §03(a) as being unpatentable
over Deeter in view of Sauraba.

FINDINGS OF FACT
The Examiner’s findings of fact are set forth in the Answer at pages 6-
11.

Appeal 2012-003855
Application 11/060,510

4
Discussion
ISSUE
The Examiner concludes that, “Deeter et al. teach the synthesis of the
compound of instant formula I via an asymmetric reduction of the ketone of
instant formula II and subsequent reaction to form duloxetine. See page
7101-7102, especially the scheme on page 7102.” (Ans. 6.) The Examiner
finds that, “Deeter et al. do not teach the rhodium catalyst for the reaction.”
(id.) The Examiner, therefore, relies on Sakuraba which discloses, “the
asymmetric reduction of extremely similar compounds (phenyl instead of
thiophene) using various pressures of H2, substrate to catalyst ratios, and
with the weak base triethylamine present. Additionally, the rhodium catalyst
is the same as in the claims and is made in situ. ” (id.)
Therefore, the Examiner concludes that,
“The motivation to combine the references lies in the fact
that reaction conditions are similar for similar compounds and
that one reaction system strongly suggests to the person of
ordinary skill that the reaction system will work on a similarly
constructed compound with a reasonable expectation of
success.”

(Ans. 6-7.)
Appellants argue that
“[It] is well-known that when using transition metal
complexes, sulfur and sulfur-containing compounds are
catalytic poisons. In light of the disclosed catalytic process,
phenyl and thiophene substitutions are not obvious variants. In
fact, a skilled artisan would have been led away from applying
the rhodium catalyst system of Sakuraba used for phenyl-
substituted compounds to the thiophene substituted compounds
Appeal 2012-003855
Application 11/060,510

5
because the skilled artisan would have believed the thiophene
would be a catalyst poison.”

(App. Br. 10.)
Appellants put forth several publications as evidence that sulfur
compounds are catalytic poisons, including Vradman, Birch, Reyes and
Rabinovich. (App. Br. 10-11.)
The issue is: Does the cited prior art support the Examiner’s
conclusion that the claimed subject matter is obvious?

PRINCIPLES OF LAW
“In rejecting claims under 35 U.S.C. § 103, the examiner bears the
initial burden of presenting a prima facie case of obviousness. Only if that
burden is met, does the burden of coming forward with evidence or
argument shift to the applicant.” In re Rijckaert, 9 F.3d 1531, 1532 (Fed.
Cir. 1993) (citations omitted). In order to determine whether a prima facie
case of obviousness has been established, we consider the factors set forth in
Graham v. John Deere Co., 383 U.S. 1, 17 (1966): (1) the scope and content
of the prior art; (2) the differences between the prior art and the claims at
issue; (3) the level of ordinary skill in the relevant art; and (4) objective
evidence of nonobviousness, if present.
“[T]he term ‘prima facie obvious’ relates to the burden on the
examiner at the initial stage of the examination, while the conclusion of
obviousness vel non is based on the preponderance of evidence and
argument in the record.” In re Oetiker, 977 F.2d 1443, 1446 (Fed. Cir.
1992).
Appeal 2012-003855
Application 11/060,510

6
“The combination of familiar elements according to known methods
is likely to be obvious when it does no more than yield predictable results.”
KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007).

ANALYSIS
We agree with the Examiner’s fact finding, statement of the rejection
and responses to Appellants’ arguments as set forth in the Answer and adopt
them as our own. We find that the Examiner has provided evidence to
support a prima facie case of obviousness. The Answer finds deficiencies
with each of Appellants’ proffered references which have not been rebutted
sufficiently by Appellants. (Ans. 8-9.) On balance Appellants have failed to
rebut the Examiner’s prima facie case of obvious by a preponderance of the
evidence.

CONCLUSION OF LAW
The cited references support the Examiner’s obviousness rejection.
The rejection is affirmed for the reasons of record.
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

lp