Ex Parte Jaekel et al

Patent Trial and Appeal Board

Dec 19, 2016

12307472 (P.T.A.B. Dec. 19, 2016)

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.
12/307,472 01/05/2009 Christoph Jaekel 336162US0PCT 3317
22850 7590 12/21/2016
OBLON, MCCLELLAND, MAIER & NEUSTADT, L.L.P.
1940 DUKE STREET
ALEXANDRIA, VA 22314
EXAMINER
SAWYER, JENNIFER C
ART UNIT PAPER NUMBER
1671
NOTIFICATION DATE DELIVERY MODE
12/21/2016 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):
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PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte CHRISTOPHE JAEKEL, WOLF-RUEDIGER KRAHNERT,
ROCCO PACIELLO, and WOLFGANG SIEGEL
Appeal 2014-006688
Application 12/307,4721
Technology Center 1600
Before DONALD E. ADAMS, JOHN G. NEW and DAVID COTTA,
Administrative Patent Judges.
COTTA, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a method
of preparing optically active 3-amino carboxylic ester compounds. The
Examiner rejected the claims on appeal as obvious under 35 U.S.C. § 103(a).
We AFFIRM.
1 According to Appellants, the real parties in interest is BASF SE, Germany.
App. Br. 1.
Appeal 2014-006688
Application 12/307,472
STATEMENT OF THE CASE
Claims 1—19 are on appeal. Claim 1 is illustrative and reads as
1. A method for preparing optically active 3-amino
carboxylic ester compounds of the general formula I, and
the ammonium salts thereof,
in which
R1 is alkyl, cycloalkyl, heterocycloalkyl, aryl, or hetaryl, and
R2 is alkyl, cycloalkyl or aryl,
in which a mixture of enantiomers, emiched in one
enantiomer, of a mono N-acylated 3-amino carboxylic
ester of the general formula (l.b),
in which R1 and R2 have the meanings indicated above,
and R3 is hydrogen, alkyl, cycloalkyl or aryl, is subjected
to a deacylation by addition of an acidic salt former, and
to a subsequent further enantiomeric emichment by
crystallization.
follows:
O
2
Appeal 2014-006688
Application 12/307,472
The Examiner rejected claim 1—19 under 35 U.S.C. § 103(a) over the
combination of Onishi,2 Boaz,3 Zhang ‘495,4 Zhang ‘604,5 and Ovenden.6
ANALYSIS
We adopt the Examiner's findings of fact and reasoning regarding the
scope and content of the prior art and agree that the claims are obvious over
Onishi, Boaz, Zhang ‘495, Zhang ‘604 and Ovenden. We address
Appellants’ arguments below.
Claims 1, 2, 4, 6—12, 15, and 16
Appellants argue claims 1, 2, 4, 6—12, 15 and 16 together as a group.
We designate claim 1 as representative of the group.
The Examiner found that Onishi disclosed the synthesis of P-amino
acids as represented in the below reaction scheme.
0 Rxn 2 0 Rxn3
r 1 •""Rx NH
X
8* ' v
A/OT
2 Onishi et. al., JP 3493206 B2, published Feb. 3, 2004 (“Onishi”).
3 Boaz et al., The Preparation of Single Enantiomer 2-Naphthy alanine
Derivatives Using Rhodium — Methyl BoPhoz-Catalyzed Asymmetric
Hydrogenation, 9 Organic Process Research & Development 2005,
472-478 (2005) (“Boaz”).
4 Zhang et al, US 2005/0119495 Al, published June 2, 2005 (“Zhang
495”).
5 Zhang, US 2005/0159604 Al, published July 21, 2005 (“Zhang ‘604”).
6 Ovenden et al., Amphilactams A-D: NovelNematocides from Southern
Australian Marine Sponges of the Genus Amphimedon, 64 (4) J. Org.
Chem., 1140-1144 (1999) (“Ovenden”).
3
Appeal 2014-006688
Application 12/307,472
Non-Final Act. 3^4. In the above reaction scheme, as described by the
Examiner, “Rxn 3 is a deacrylation reaction with an acid (e.g. hydrochloric
acid) to give the free amine” enriched in the R enantiomer. Id. at 3. The
Examine further found that Onishi taught “the generality of the reaction to
not only carboxylic acids, but also to ester compounds.” Id. at 4.
The Examiner acknowledged that Onishi did not teach enantiomeric
enrichment by crystallization as recited in claim 1, but found that this
element was supplied by Boaz. Id. at 4. The Examiner found that Boaz
taught the synthesis of a-amino acids using enantioselective hydrogenation
to give “an enriched enantiomeric mixture of the ester,” followed by “an N-
deacylation reaction ... to give the free amine as the R enantiomer.” Id.
The Examiner found that Boaz further taught that “enhancement of the ee
[enantiomeric excess] can be achieved by crystallization with
methanesulfonic acid to form the salt.” Id. The Examiner further found that
crystallization was a common laboratory procedure, and an obvious
purification method. Id. at 5.
Appellants argue that the reaction described in Onishi discloses the
stereoselective hydrogenation of an N-acylated, a-unsaturated (Z)-3 amino
carboxylic acid and that this method cannot be applied to esters. App. Br. 8—
9. We are not persuaded.
In finding that the method of Onishi could be extended to esters, the
Examiner relied on Onishi’s discussion of the “Prior art and Problems to be
Resolved by the Invention.”7 Ans 2—3; Onishi 13^4. Among the problems
7 The Examiner also found that “the acid and ester functionality are not
involved in the chemical transformation in question and are merely
bystander functional groups.” Ans. 3.
4
Appeal 2014-006688
Application 12/307,472
discussed in Onishi are asymmetric hydrogenation reactions for obtaining
esters including 3-acetamidobutanoic acid methyl ester, 3-acetamido-5-
methylhexanoic acid methyl ester and 3-acetoxy-3-phenylhexanoic acid
methyl ester. Onishi 14. Onishi describes the problems as follows:
[W]ith asymmetric hydrogenation reactions in which
ruthenium complexes are used as [a] catalyst it has been
reported [Tetrahedron Asymmetry, 1991, 2, 543-554]
that 3-acetamidobutanoic acid methyl ester was obtained
with an optical purity of 96% ee with (E)-3-acetamido-2-
butenoic acid methyl ester as substrate and that 3-
acetamido-5-methylhexanoic acid methyl ester and 3-
acetoxy-3-phenylhexanoic acid methyl ester with optical
purities of 90% ee were obtained from (E)-3-actamido-5-
methyl-2-hexenoic methyl ester and (E)-3-acetamido-3-
phenyl-2-propenoic acid methyl ester respectively, but in
this report it is also indicated that while in those cases
where the olefin-acid ester[,] which was the substrate[,]
had the (E) form configuration[,] the hydrogenated
product had a high optical purity, in those cases where
geometrical isomers which had the (Z) form
configuration were used as substrates the hydrogenated
products had a low optical purity with a maximum of 9%
ee.
Id.
After discussing the “Prior Art and Problems to be Resolved by the
Invention,” including problems with relating to ester compounds, Onishi
provides a discussion entitled “Means of Resolving These Problems.” Id. at
1 5. Onishi proceeds to discuss the stereoselective reaction relied upon by
the Examiner. Based on the plain language of Onishi, the reaction relied
upon by the Examiner, which is exemplified by an N-acylated, a-unsaturated
(Z)-3 amino carboxylic acid, solved the problems described in the “Prior Art
and Problems to be Resolved by the Invention” section. As these problems
included stereoselection in ester compounds, the record supports the
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Application 12/307,472
Examiner’s finding that Onishi’s solution — exemplified using carboxylic
acid — extended to ester compounds.
Appellants disagree with the Examiner’s interpretation of paragraph 4
of Onishi, but the Examiner’s interpretation is supported by the plain
language of the reference. Appellants argue that Onishi’s teaching that ester
isomers in the Z configuration had low optical purity would have
discouraged the person of ordinary skill from applying Onishi’s methods to
esters (App. Br. 9), and reflects the unpredictability of working with esters.
Reply Br. 5—6. As discussed above, however, Onishi teaches that its method
resolves these problems. After reviewing the record, we find that Appellants
have not established a persuasive evidentiary basis to support their
contention that the Examiner is wrong that Onishi’s teachings apply to
esters. See Johnston v. IVAC Corp., 885 F.2d 1574, 1581 (Fed. Cir. 1989);
(“Attorneys’ argument is no substitute for evidence.”); In re Pearson, 494
F.2d 1399, 1405 (CCPA 1974).
Appellants argue that the Examiner erred in combining the teachings
of Boaz with those of Onishi because Boaz relates to a-amino acids while
Onishi relates to P-amino acids. App. Br. 10. Appellants argue that the
Examiner failed to articulate a reason why a person of ordinary skill in the
art would substitute a-amino acids and P-amino acids. Id. We are not
persuaded that Appellants have identified reversible error.
The Examiner relied upon Boaz for its teaching that optical purity
could be was enhanced by crystallization. Ans. 6. The Examiner found that
crystallization was a common laboratory purification procedure. Non-Final
Act. 5. Appellants have not established a persuasive evidentiary basis on
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Application 12/307,472
which to find that a teaching that crystallization enhances the purity of a-
amino acids would not apply to P-amino acids.
Appellants allege that the claimed method provides unexpected results
in that it produces “optically active 3-amino carboxylic esters with an
enantiomeric excess (ee) of approximately at least 98%.” App. Br. 10.
Appellants contend “[tjhere is no disclosure in the prior art of a process of
forming comparably optically active 3-amino carboxylic esters.” Id. at 11.
We are not persuaded because Appellants do not compare the ee optical
purity of 3-amino carboxylic esters produced using its method to the purity
of 3-amino carboxylic esters obtained by any other method.
Accordingly, we affirm the Examiner’s rejection of claim 1 over the
combination of Onishi, Boaz and Ovenden. Because they were not argued
separately, claims 2, 4, 6—12, 15 and 16 fall with claim 1.
Claim 3
Claim 3 depends from claim 2 and additionally requires that “a 8-keto
ester of the formula 1.1 is reacted with at least one carboxamide of the
formula R3-C(0)NH2 in the presence of an amidation catalyst with removal
of the water of reaction to give a 3-amino carboxylic ester of the formula
I.a.” In their opening brief, Appellants argued that the Examiner “failed to
establish where in any of the cited references this reaction is disclosed.”
App. Br. 11. The Examiner’s Answer specifically identified this reaction as
being disclosed in Ovenden. Ans. 11—12. Appellants do provide any reason
why the Examiner’s identification of this reaction as being disclosed in
Ovenden is in error, instead arguing that claim 3 is patentable for the reasons
1, 2, 4, 6—12, 15 and 16 are patentable. Reply Br. 15—16. Accordingly, we
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Application 12/307,472
affirm the Examiner’s rejection of claim 3 for the reasons already provided
in connection with claims 1, 2, 4, 6—12, 15 and 16.
Claim 5
Claim 5 depends from claim 1 and additionally requires that “the
enantiomer-enriching crystallization is carried out with addition of an ester.”
The Examiner found that crystallization using different solvents was a
common laboratory procedure (Non-Final Act. 5), and provided several
examples where ethyl acetate — an ester — was used in purification and
recrystallization procedures. Ans. 13 (citing examples from Zhang ‘495,
Ovenden and Boaz).
Appellants argue that the examples provided by the Examiner do not
involve the claimed 3-amino carboxylic compounds and additionally, with
respect to two of the four examples cited by the examiner, do not involve
recrystallization. Reply Br. 17—21. We are not persuaded. The examples
provided by the Examiner establish that ethyl acetate, an ester, is a solvent
that is useful for purification and recrystallization. Having established,
based on Boaz, that recrystallization enhances enantiomeric purity, it would
have been obvious to carry out recrystallization with a solvent, like ethyl
acetate, that is known to be useful for purification and recrystallization.
Accordingly, we affirm the Examiner’s rejection of claim 5.
Claims 13 and 14
Claims 13 and 14 depend from claim 2 and additionally require that at
least one step of claim 2 is carried out “continuously.” Claim 14 further
specifies that the continuous reaction is hydrogenation.
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Application 12/307,472
The Examiner contends that continuous reactions are common process
modifications. Non-Final Act. 6. The Examiner notes that Boaz “teaches
the scale-up potential of the synthesis.” Id. The Examiner further notes that
Onishi discloses performing the hydrogenation reaction for 24 hours and
Boaz teaches performing hydrogenation for 6 hours. Ans. 14. Appellants
argue that the claims do not require scale up and that the disclosures
“highlight that the processes of Onishi and Boaz are carried out in a single
distinct stage rather than being performed continuously.” Reply Br. 22.
We find that the Examiner has the better position. In arguing that a 24
hour hydrogenation reaction (as disclosed in Onishi) is not “continuous”
because it is “carried out in a single distinct stage,” Appellants implicitly
contend that the term “continuous” should be construed to require that the
reaction continue indefinitely with no temporal end point (or at least for a
period longer than 24 hours). Reply Br. 22. We do not agree with this
construction. Instead, we find that the term “continuous” is more reasonably
construed to mean “without interruption.” This is consistent with how the
term is used in the Specification. See, Specification 15. Appellants do not
identify any disclosure in Onishi or Boaz teaching interruption of the
hydrogenation reaction. Accordingly, we affirm the Examiner’s rejection of
claims 13 and 14.
Claims 17 and 19
Claims 17 and 19 depend from claim 1. Claim 17 adds a limitation
requiring that “the value of ee for the solid isolated after the crystallization is
at least 98%.” Claim 19 adds a limitation requiring that the optically active
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Appeal 2014-006688
Application 12/307,472
3-amino carboxylic ester compounds produced have an enantiomeric excess
of at least 98%.”
Appellants argue that it the claimed purity would not have been
obvious because it was not predictable. Reply Br. 23—25. We disagree. A
newly-discovered result or property of an existing (or obvious) method of
use is not patentable. See Abbott Labs. v. Baxter Pharm. Prods., 471 F.3d
1363, 1368-69 (Fed. Cir. 2006); Brassica Prot. Prods. LLCv. Sunrise Farms
(In re Cruciferous Sprout Litig.), 301 F.3d 1343, 1350-51 & n.4 (Fed. Cir.
2002); and Bristol-Myers Squibb Co. v. Ben Venue Labs., 246 F.3d 1368,
1376 (Fed. Cir. 2001). Accordingly, we affirm the Examiner’s rejection of
claims 17 and 19.
Claim 18 depends from claim 1 and additionally requires that “an
optically active compound of the formula II or the ammonium salts thereof
with the following absolute configuration, or the optically active enantiomer
of this compound or salts, is obtained,
where R2 is C1-C6 alkyl.”
The Examiner’s reasoning and Appellants’ arguments with respect to
claim 18 are substantially the same as their reasoning and arguments with
respect to claim 1. Accordingly we affirm the Examiner’s rejection of claim
Claim 18
HM H O
d (II)
OR2
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Application 12/307,472
18 for the reasons discussed provided above with respect to claims 1, 2, 4,
6—12, 15 and 16.
SUMMARY
For these reasons and those set forth in the Examiner’s Answer, and
the Non-Final Office Action, the Examiner’s Final decision to reject claims
1—19 is affirmed.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(1).
AFFIRMED
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