Ex Parte Wang et al

Patent Trial and Appeal Board

Oct 12, 2017

13831706 (P.T.A.B. Oct. 12, 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.
13/831,706 03/15/2013 Yong Wang 107900.00003 3894
29880 7590 10/16/2017
FOX ROTHSCHILD LLP
PRINCETON PIKE CORPORATE CENTER
997 LENOX DRIVE
BLDG. #3
EAWRENCEVTT.TE, NJ 08648
EXAMINER
RODRIGUEZ-GARCIA, VALERIE
ART UNIT PAPER NUMBER
1626
NOTIFICATION DATE DELIVERY MODE
10/16/2017 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
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PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte YONG WANG, CANG ZHANG, and XIAOXIN TAO1
Appeal 2016-001378
Application 13/831,706
Technology Center 1600
Before JEFFREY N. FREDMAN, RICHARD J. SMITH, and
DAVID COTTA, Administrative Patent Judges.
SMITH, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a method
for treating a parasitic infection comprising administration of L-enantiomer
enriched omidazole. We have jurisdiction under 35 U.S.C. § 6(b).
We affirm.
1 According to Appellants, the real party in interest is Nanjing Sanhome
Pharmaceutical Co., Ltd. (Appeal Br. 4), which is also identified as one of
the Applicants.
Appeal 2016-001378
Application 13/831,706
STATEMENT OF THE CASE
Claims on Appeal
Claims 1, 3—6, 8—11, and 13—21 are on appeal. (Claims Appendix,
Appeal Br. 33—34.) Claims 1 and 6 are illustrative and read as follows:
1. A method for treating a parasitic infection, comprising
administering to a patient in need of treatment a therapeutically effective
amount of L-enantiomer enriched omidazole, or a pharmaceutically
acceptable salt or solvate thereof, wherein said L-enantiomer enriched
omidazole has an enantiomeric excess of at least 90.0%.
(Id. at 33.)
6. A method for treating a parasitic infection in a patient,
comprising administering to the patient a pharmaceutical composition
comprising a therapeutically effective amount of L-enantiomer enriched
omidazole, or a pharmaceutically acceptable salt or solvate thereof, and a
pharmaceutically acceptable carrier, wherein the L-enantiomer enriched
omidazole has an enantiomeric excess of at least 90.0%.
(Id.)
Examiner’s Rejections
1. Claims 1, 3—6, 8—11, and 13—21 stand rejected under 35 U.S.C.
§ 103(a) as unpatentable over Bone2 or Tian,3 Giiven,4 Weitgasser,5
2 W. Bone et al., Toxicity of omidazole and its analogs to rat spermatozoa
as reflected in motility parameters, Inti. J. Androl. 20(6), 347—55 (1997)
(“Bone”).
3 P. Tian et al., Lipase-Catalyzed Resolutions of both Enantiomers of
Omidazole and Secnidazole, Chinese J. Chem. 21, 853—57 (2003) (“Tian”).
4 A. Giiven, Amebiasis in the Newborn, Indian J. Pediatr. 70(5), 437—38
(2003) (“Giiven”).
5 H. Weitgasser, Treatment of Vaginal Trichomoniasis Using Tiberal,
Wiener Medizinische Wochenschrift 126(11—12), 162—65 (1976)
(“Weitgasser”).
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Williams,6 Ansel,7 Mahato,8 Windheuser,9 Pather,10 and Jivraj.* 11 (Ans. 3—7.)
2. Claims 1, 3—6, 8—11, and 13—21 stand provisionally rejected on the
ground of nonstatutory double patenting as being unpatentable over claims
60, 63, 64, 67—69, and 71—79 of copending Application No. 11/909,623. (Id.
at 20-21.)12
The Examiner also objected to the Specification based on use of the
trademark OPADRY, which the Examiner stated “should be capitalized
whenever it appears and be accompanied by the generic terminology.”
(Final Act. 2, dated Aug. 20, 2014.) Appellants state that they “shall amend
the specification to correct the alleged informality accordingly at the next
opportunity available.” (Reply Br. 15.)
FINDINGS OF FACT
FF 1. The Specification states that omidazole contains two
enantiomers, the (S)-(-)-enantiomer (also referred to as levo-omidazole, F-
6 Williams et al., Foye’s Principles of Medicinal Chemistry 50 (5th Ed.)
(2002) (“Williams”).
7 H.C. Ansel, Ph.D., Pharmaceutical Dosage Forms and Drug Delivery
Systems 92—182 (5th ed., Fea & Febiger) (1990) (“Ansel”).
8 R.I. Mahato, Ph.D., Dosage Forms and Drug Delivery Systems, APhA’s
Complete Review for Pharmacy, (Gourley DR, ed.), 3rd ed., Castle Connolly
Graduate Med. Publ., New York, 37—63 (2005) (“Mahato”).
9 Windheuser, US 4,289,751, issued Sept. 15, 1981 (“Windheuser”).
10 Pather et al., US 6,576,250 Bl, issued June 10, 2003 (“Pather”).
11 M. Jivraj et al., An overview of the different excipients useful for the direct
compression of tablets, Pharm. Sci. & Tech. Today 3(2), 58—63 (2000)
(“Jivraj”).
12 Appellants state that they “shall submit a Terminal Disclaimer accordingly
to overcome the provisional double patenting rejection when any of the
rejected claims is found to be allowable.” (Reply Br. 15.) Accordingly, we
will not further address this rejection.
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omidazole, or L-enantiomer) and the (R)-(+)-enantiomer (also referred to as
dextro-omidazole, D-omidazole, or D-enantiomer). (Spec. 13.)
FF 2. The Specification states that the racemic mixture of omidazole
“has been known for over 30 years and used for treatment of parasitic
infections.” (Id. 14, citing Giiven 37—38.)
FF 3. The Specification states that
the present inventors studied the two enantiomers of omidazole
more systematically on their anti-parasitic activity and toxicities,
since development of a chiral omidazole dmg using only one of
the enantiomers as the active ingredient could provide benefits
such as higher efficacy and/or better safety profile over the
existing racemic omidazole dmg. In particular, adverse events
and toxicities, mostly occurring in the central nervous system,
have limited the use of racemate omidazole, and the toxicities of
the racemic mixture of omidazole may prevent long-term use in
treating infections. Therefore, there has been a need to design
and conduct appropriate research and clinical trials in order to
realize the full potential and benefits of omidazole in treating
parasitic infections.
(Id. 17.)
FF 4. The Specification states that:
The present invention fulfills the foregoing need by providing a
single enantiomer, the L-omidazole, or L-enantiomer-enriched
omidazole, as an anti-parasitic agent based on the surprising
discovery of the differences between L- and D-isomers of
omidazole in toxicity profiles, in particular the markedly lower
toxicity of L-isomer to the central nervous system (CNS).
(Id. 1 8.)
FF 5. The Examiner finds that “Bone teaches a pharmaceutical
composition of L-enantiomer enriched omidazole (only L (S)-omidazole)
and how to obtain it.” (Ans. 4.) Bone also states that “[t]he putatively
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inactive (R)- and the active (S)-omidazole exhibited equivalent depression
of sperm motility by direct incubation.” (Bone, 347, Summary (Abstract).)
FF 6. The Examiner finds that “Tian teaches the separation of
omidazole enantiomers and preparation of a composition of L-enantiomer
enriched omidazole (see (S)-omidazole >99%ee []).” (Ans. 4, citing Tian
856.)
FF 7. The Examiner finds that Tian “teaches the motivation and
expectation for finding one enantiomer better than the other in the excerpt:
‘If the active enantiomer of the racemate could be use[d], the dos[ag]e might
be halved. So the necessity of gaining the optically pure enantiomers of
omidazole and secnidazole is quite obvious.’” (Ans. 4, citing Tian 853.)
FF 8. The Examiner finds that Williams teaches that:
[W]hen introduced into an asymmetric, or chiral, environment,
such as the human body, enantiomers will display different
physical chemical properties producing significant differences in
their pharmacokinetic and pharmacodynamic behavior. Such
differences can result in adverse side effects or toxicity due to
one of the isomers[,] or the isomers may exhibit significant
differences in absorption [(especially active transport)], semm
protein binding and metabolism.
(Ans. 5—6, citing Williams 50, col. 1.)
DISCUSSION
Except as otherwise indicated, we adopt the Examiner’s findings and
conclusions as our own, including with regard to the scope and content of,
and motivation to combine, the prior art, as set forth in the Answer (Ans. 3—
22). We discern no error in the rejection of the claims as obvious.
Issue
Whether a preponderance of evidence of record supports the
Examiner’s rejection under 35 U.S.C. § 103(a).
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Analysis
Appellants contest the obviousness rejection by arguing that a prima
facie case has not been established and, if a prima facie case of obviousness
has been established, that Appellants rebut that prima facie case with
unexpected results and secondary considerations. (See Appeal Br. 7—31 and
Reply Br. 5—15.) Appellants argue claims 1, 3—6, 8—10, and 16 as a group,
from which we select claim 1 as representative, and dependent claims 11,
13—15, and 17—21 as a group, from which we select claim 18 as
representative.
Prima Facie Obviousness
The Examiner’s position, based on the findings (see, e.g., FF 2 and 5—
8), is stated in the Answer as follows:
The enantiomers have been previously separated into a
pure composition of F-omidazole and a pure composition of D-
omidazole (Bone, Tian). The pharmaceutical composition used
in these claims was known. The treatment of parasitic infections,
e. g. trichomonas vaginalis, cecal amoeba infection, with
omidazole was known ([Guven], Weitgasser). The ordinary
skilled artisan would have been motivated to use the best
enantiomer of omidazole for the treatment of parasitic infections
treatable with racemic omidazole, because a person of ordinary
skill in the art would have known that a single isomer (e. g. a
single enantiomer) is often therapeutically superior to the
racemic mixture and to the other isomer and each separate
enantiomer was available (Bone, Tian).
(Ans. 5.)
The Examiner also states that:
ft appears as though Applicant has determined experimentally
what a person of ordinary skill in the art was expecting, that the
two enantiomers of omidazole possess substantially different
pharmacological activity. It follows that being presented only
with two options, namely the F- and D-enantiomers, the skilled
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artisan would choose the better of the two. Therefore, treatment
with said L-enantiomer enriched omidazole (of at least 90.0% ee,
or 95.0% ee, or 99% ee) as instantly claimed would have been
obvious over the known treatment with the racemic mixture.
(Id. at 6.)
Appellants ’ Arguments
Appellants argue that Bone and Tian teach away from the claimed
invention because “Bone and Tian[] disclose that there is no significant
difference in physiological activity or toxicity between the two enantiomers
of omidazole.” (Appeal Br. 8—10.) Appellants point to Bone’s statement
that “the putatively inactive (R)- and the active (S)-omidazole exhibited
equivalent depression of sperm motility by direct incubation.” (Id. at 9,
citing Bone Abstract; see FF 5.) Appellants also point to Tian’s teachings
(FF 7), which Appellants refer to as “the conventional belief,” and argue that
“the results from the present invention are in sharp contrast with Tian’s
proposition, because the efficacy difference of L- and D-omidazoles in
treating parasitic infections is only about 10%, a far cry from the ‘one active,
the other inactive’ scenario suggested by Tian and Bone.”13 (Id. at 9—10.)
Thus, according to Appellants, “the results disclosed in the present invention
. . . are unexpected in view of Bone and Tian.”14 (Id. at 10.)
13 Appellants also contend that “Tian acknowledged the teaching-away of
Bone,” referring to Tian’s Chinese patent application counterpart (CN
1400312A (“Lin”)) cited in parent Application No. 11/909,623 (“the parent
application”). (Appeal Br. 10.) Appellants appear to equate Lin with Tian.
(Id.)
14 We address unexpected results below, and view this statement as also in
support of Appellants’ “teaching away” argument.
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Appellants also point to “the substantial higher costs associated with
manufacturing a single enantiomer,” and that “separation of L-omidazole
from the racemic mixture would mean discarding the other half of only
slightly less active D-enantiomer.” (Appeal Br. 10.) Appellants also argue
that Giiven and Weitgasser only disclose use of racemic omidazole, that
Williams is cumulative to Tian and Bone, and that the USFDA Document15
does not teach that L-enantiomers are routinely less toxic. (Id. at 10—12.) In
addition, Appellants rely on the Declaration of Yong Wang16 to argue that
“there is no suggestion in [] Bone or Lin that the D-omidazole or L-
omidazole isomers possess differing characteristic regarding either
therapeutic efficacy or toxicity.”17 (Appeal Br. 12, citing Decl. 3—6.)
In response, we do not find that Bone or Tian teach away from the
claimed invention because neither reference criticizes, discredits, or
otherwise discourages the claimed invention. See In re Fulton, 391 F.3d
1195, 1201 (Fed. Cir. 2004). Bone’s teachings are directed to depression of
sperm motility (Ans. 8) and Tian actually encourages the skilled artisan to
seek optically pure enantiomers of omidazole (FF 7). The USFDA
15 USFDA, Development of New Stereoisomeric Dmgs, 1—4 (1992)
(“USFDA”). The Examiner cites USFDA in response to Appellants’
contention of unexpected results. (Ans. 7.)
16 Declaration of Yong Wang (Pursuant to 37 C.F.R. Section 132) (dated
Nov. 24, 2011) (“Wang Declaration” or “Decl.”). The Wang Declaration
was submitted in the parent application.
17 Appellants also contend, based on the Wang Declaration, that “these
references provide no reasonable expectation of success in testing a single
enantiomer on animals or humans.” (Appeal Br. 12.) However, the claims
are not directed to a testing method. Also, while Appellants argue “an undue
amount of experimentation would be needed” (id. at 13), that statement is
merely attorney argument and unsupported by evidence.
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document states that “there are instances in which toxicity has been linked to
one member of a pair of stereoisomers,” and provides several examples of
toxic D-isomers, which would have motivated the skilled artisan to explore
differences between and among stereoisomers.18 (USFDA 2.) Finally, the
Wang Declaration merely provides conclusory opinions regarding Wang and
Lin without addressing the specific substance of their respective teachings as
set forth by the Examiner. (See Deck 4 and 6.)
Unexpected Results
In addition to arguments regarding Bone and Tian, Appellants rely on
the Wang Declaration and attached data to argue that “this invention shows
that L-omidazole has markedly diminished CNS toxicity and about 10%
higher pharmacological activity than D-omidazole.” (Appeal Br. 15.)
Appellants further argue that “surprisingly, the L-isomer has slightly higher
activity but markedly lower CNS toxicity than the corresponding D-isomer,”
and that “L-omidazole possesses properties so different in kind or magnitude
that they would have been totally unexpected to one skilled in the art.” {Id.
at 16.) Appellants also argue that
nonobviousness of the invention [is] based on the fact that L- and
D-omidazoles have only about 10% different efficacy, but
markedly different CNS toxicity, which is surprising and
unexpected. The data supports superiority of L-omidazole in the
treatment of parasitic infections mainly because it would cause
less, if any, toxicity to a patient, not because it is much more
18 Appellants’ issue with respect to the Examiner’s reliance on the USFDA
document appears to relate to the Examiner’s characterization of L-
enantiomers as “routinely” less toxic. While that characterization is not
necessarily incorrect, we do not adopt the Examiner’s characterization of
“routinely” for purposes of this Decision.
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efficacious, though 10% better efficacy certainly makes L-
omidazole, to some extent, more beneficial to the patient.
(Reply Br. 11.)
Appellants rely on experiments and results summarized in paragraph 2
of the Wang Declaration. (Appeal Br. 15—16.) While those studies include
comparisons between the D- and L-enantiomers, the pertinent studies are
those comparing L-enantiomer to the racemate because the omidazole
racemate is the closest prior art.19 In re Baxter TravenolLabs., 952 F.2d
388, 392 (Fed. Cir. 1991) (“[W]hen unexpected results are used as evidence
of nonobviousness, the results must be shown to be unexpected compared
with the closest prior art.”). Studies identified in the Wang Declaration that
include a comparison between L-omidazole and the racemate include the
following:
Section 2.3 compares the effect on spontaneous activities in mice,
concluding the existence of a “dose-effect” wherein L-omidazole shows
significantly less inhibitory effects than the racemate at a dose of 160 mg/kg.
(Deck 12 and Appendix 1, 16—18.)
Section 2.4 compares the effects on motor balance and coordination in
mice, concluding that L-omidazole shows significantly less influence on
motor balance and coordination than the racemate at a dose of 160 mg/kg.
(Deck 12 and Appendix 1, 19—20.)
Section 2.5 compares the hypnotic effects, concluding that, at a dose
of 160 mg/kg, none of the mice in the L-omidazole group lost righting flex,
whereas 6 out of 10 mice in the racemate group lost righting flex, indicating
19 While the D- and L- enantiomers had been separated and Appellants focus
on the differences between them, the racemic omidazole was used to treat
parasitic infections. (FF 2, 5, and 6.)
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stronger hypnotic effects by the racemate. (Decl. 2 and Appendix 1,21—
23.)
Section 3 compares toxicity at an IV dose of 200 mg/kg in Beagle
dogs, concluding (in part) that L-omidazole exhibited mild toxicity whereas
the racemate exhibited moderate toxicity. (Decl. 12 and Appendix 1, 23—
29.)
Section 5 compares adverse events20 in clinical studies and concludes
(in part) that “[d]ata from the phase I clinical trials demonstrate that
racemate omidazole causes markedly more adverse events than levo-
omidazole at a regular human dose level of 1 gram.” (Decl. 12 and
Appendix 1, 35 40.) The Wang Declaration summarizes the Section 5
clinical trials data by stating that “patients experience significantly] less
adverse events in the levo-omidazole group than in the racemate group. All
the observed adverse events are related to inhibition of the central nervous
system.” (Id. at 40.)
Response
Appellants’ evidence of unexpected results raises at least three issues:
1. Unexpected results must be shown to be unexpected compared
with the closest prior art, and the mere recognition of latent properties in the
prior art does not render nonobvious an otherwise known invention. Baxter
Travenol, 952 F.2d at 392 (citing cases). Here, Appellants do not provide
persuasive evidence that the results obtained are unexpected compared with
the closest prior art (racemic omidazole), or other evidence that the results
20 The data identify “adverse events” as symptoms such as headache,
vomiting, and dry mouth. (See Wang Declaration, Appendix 1, 36-40.)
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reflect something other than the mere recognition of latent properties in the
prior art.
Appellants argue that Bone teaches that toxicity differences between
D- and L-enantiomers would not be expected based on its teaching of
“equivalent depression of sperm motility.” (Appeal Br. 8—10.) Appellants
also argue that the minor activity difference discovered by Appellants
(between D- and L-enantiomers) was unexpected in view of Tian’s “one
active, the other inactive” teaching, as Appellants characterize Tian’s
teaching (FF 7). (Id.; see also Reply Br. 9—10.)
As to Bone, Appellants point to Bone’s statement that “[a]
comparison of the motility-inhibiting efficacy of (R)- and (S)-omidazole
(Fig. 3) on spermatozoa directly incubated for 4 h revealed no differences
between the enantiomers (Fig. 4).” (Appeal Br. 9, citing Bone 350, rt. col.)
As reflected in Fig. 4 of Bone, the “no differences” refers to motility
parameters of straight line velocity (VSL), curvilinear velocity (VCL), and
linearity (LIN) at different concentrations of the racemic mixture and
enantiomers separately. (Bone, 349, left col. and 350, rt. col., Fig. 4.)
Appellants, however, do not provide persuasive evidence to explain how and
why the similarities in depressing sperm motility should be extended to the
toxicity associated with treating parasitic infections in patients to which the
present application is directed. (See FF 3, 4.) As to Tian’s alleged teaching
of enantiomers as “one active, the other inactive,” we note that Tian’s actual
statement is that “[i]f the active enantiomer of the racemate could be used,
the dosage might be halved.” (Tian 853; FF 7.) Tian also states that “[t]he
bioactivity test is in progress, which will reveal the relationships between
configuration and bioactivities.” (Tian 854, rt. col.) As such, we do not find
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Appellants’ argument that their results “are unexpected in view of Bone and
Tian” to be particularly persuasive.
In contrast, the prior art indicates that differences in activity and
toxicity between D- and L-enantiomers are to be expected. (FF 7; see also
USFDA 1—2.) Moreover, it has been held that a general teaching of activity
differences between two stereoisomers is sufficient to show that activity
differences between two specific isomers would be expected. See In re
Adamson, 275 F.2d 952, 955 (CCPA 1960). Accordingly, given the activity
and toxicity of racemic omidazole (FF 1—4), we find that it would not have
been unexpected that both enantiomers would have an activity and toxicity
profile and that those respective profiles would differ to some extent from
each other and the racemic omidazole.
2. Claim 1 recites administration to a “patient,” which is defined
in the Specification as “any mammalian animal that is inflicted with a
parasitic infection(s) needing treatment” (Spec. 1105), and is not limited to
a particular dosage regimen. However, evidence of unexpected results must
be commensurate in scope with the claimed invention. See In re Dill, 604
F.2d 1356, 1361 (CCPA 1979) (although affidavit of co-inventor
demonstrated “markedly superior results,” it did not establish unexpected
results because the evidence was not commensurate in scope with the
claims). Here, the experimental data was obtained from mice, Beagle dogs,
and humans. But essentially all of the pertinent data (comparing L-
omidazole to the racemate) that reflects an improvement in toxicity is
limited to a particular dosage or dosage regimen (such as 160 mg/kg) and
thus is not commensurate in scope with the claimed invention. (See above.)
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3. “[Differences in degree” of a known and expected property are
not as persuasive in rebutting obviousness as differences in “kind” (i.e., a
new property dissimilar to the known property). Bristol-Myers Squibb Co.
v. Teva Pharms. USA, Inc., 752 F.3d 967, 977 (Fed. Cir. 2014). Here, the
omidazole racemate was known to be toxic (FF 3), and any decrease in
toxicity exhibited by one of the two enantiomers would be a difference in
degree of toxicity rather than kind. The same is true with respect to any
efficacy difference.
Hindsight
Appellants argue that the Examiner erred “by relying on hindsight.”21
(Appeal Br. 16—19.) However, rather than using hindsight, the Examiner
points to specific disclosures in the prior art that describe the limitations of
Appellants’ claimed invention. (See, e.g., FF 5 and 6.) The Examiner also
provides reasoning, supported by the references, why a person of ordinary
skill in the art would have combined the teachings of the prior art. (FF 7 and
8; see also Ans. 5—6.) We therefore find that the Examiner’s obviousness
conclusion is based on sufficiently articulated reasoning that overcomes any
concerns about hindsight bias. See KSR Int’l Co. v. Teleflex Inc., 550 U.S.
398,418 (2007).
Secondary Considerations
Appellants argue failure of others, long-felt but unsolved need, praise
by others and industrial and governmental recognitions, and commercial
success. (Appeal Br. 19—22.) All of those arguments share a common
21 Appellants also contend that the Examiner erred in relying on the “obvious
to try” line of reasoning. (Appeal Br. 17.) However, the Examiner explains
that the “obvious to try” line of reasoning is not relied on. (Ans. 14—16.)
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weakness in that they are based on attorney argument rather than evidence
supported by an affidavit or declaration.
In arguing failure of others and long-felt but unsolved need,
Appellants point to Tian’s statement that the ‘“bioactivity test is in progress,
which will reveal the relationships between configuration and bioactivities
of these two chiral drugs.’” (Appeal Br. 19—20, citing Tian 854.)
Appellants contend that Tian has not published any such test data and that
(1) “such non-disclosure by Tian et al. is direct evidence of ‘failure of
others,’ because apparently Tian et al. had tried to find ‘the better of the two’
omidazole enantiomers, but failed,” and (2) “Tian et al. appeared to have felt
the need, and indeed had tried, to distinguish and identify the better between
the two omidazole enantiomers twelve years ago, but apparently they did not
succeed.” (Appeal Br. 20.) But those are mere attorney arguments, based
on speculation or conjecture, and not evidence. See Estee Lauder Inc. v.
L’Oreal, S.A., 129 F.3d 588, 595 (Fed. Cir. 1997) (attorney argument cannot
take the place of evidence). Furthermore, our reviewing court has
emphasized the importance of actual evidence because “‘[ajbsent a showing
of long-felt need or the failure of others, the mere passage of time without
the claimed invention is not evidence of nonobviousness.’” In re Kahn, 441
F.3d 977, 990-91 (2006) (citing cases).
Appellants’ arguments regarding praise refer to “numerous peer-
reviewed articles,” that “researchers from both academic and industrial
settings confirmed the benefits of the present invention,” and further
reference awards in China and patent grants in other major countries.
(Appeal Br. 20-21.) However, Appellants fail to establish with evidence any
nexus between such articles, benefits, or awards/patents and the claimed
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invention.22 See Wyers v. Master Lock Co., 616 F.3d 1231, 1246 (Fed. Cir.
2010) (“For objective evidence of secondary considerations to be accorded
substantial weight, its proponent must establish a nexus between the
evidence and the merits of the claimed invention”) (internal citation,
quotation marks, and bracketing omitted).
Appellants argue “commercial success” by stating that “since its
launch in China in 2010, the sales of the L-omidazole drug product in China
for the treatment of parasitic infections increased rapidly year over year from
2010 to 2013,[] while the sales of racemic omidazole were declining in the
same period, according to the IMS data.” (Appeal Br. 21.) Appellants
further state that “[m]ore recent data have shown that the 2014 sales of L-
omidazole by the patent holder in China have increased 57.7% to 70.98
million CNY from the 2013 sales of 45.0 million CNY, while the IMS data
on the full-year 2014 sales of racemic omidazole are not yet available at this
time.” (Id. atn.l.)
Commercial success “is relevant in the obviousness context only if
there is proof that the sales were a direct result of the unique characteristics
of the claimed invention—as opposed to other economic and commercial
factors unrelated to the quality of the patented subject matter.” In re Huang,
100 F.3d 135, 140 (Fed. Cir. 1996). “In other words, a nexus is required
between the sales and the merits of the claimed invention.” Id. Here, no
such nexus is established by Appellants. Moreover, Appellants state an
increase in sales in 2014, but “provide[] no indication of whether this
22 While corresponding patents may have been awarded in different
countries, the patent requirements often differ in significant ways from
country to country.
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represents a substantial quantity in [the relevant] market. Th[e] court has
noted in the past that evidence related solely to the number of units sold
provides a very weak showing of commercial success, if any.” Id-
Analysis of Claim 1
Appellants have presented evidence of a difference in efficacy (albeit
slight) between L-omidazole and D-omidazole, and a difference in toxicity
between L-omidazole and both D-omidazole and racemic omidazole.
However, as discussed above, we find that such evidence is not shown to be
unexpected, is not commensurate in scope with claim 1, and is a mere
difference in degree rather than kind. The arguments regarding secondary
considerations are based on attorney argument rather than evidence
supported by an affidavit or declaration that properly establishes the
respective criteria for the secondary consideration.
We weigh that evidence of unexpected results and those arguments
regarding secondary considerations with the evidence of obviousness. The
evidence of obviousness includes prior art that establishes the use of racemic
omidazole for treating parasitic infections, the existence of the D- and L-
enantiomers (including an enantiomeric excess of at least 90.0%) of L-
omidazole, a recognition that the two enantiomers may have different
properties, and a motivation to determine which of the two enantiomers
might be more advantageous. (See FF 1—8 and Ans. 5—6.) In our view, the
strong evidence of obviousness outweighs the relatively weaker evidence
and arguments of nonobviousness proffered by Appellants.
In consideration of all of the evidence and arguments, we find that the
Examiner has established a prima facie case of obviousness and that
Appellants have not persuasively overcome or rebutted that prima face case.
17
Appeal 2016-001378
Application 13/831,706
Accordingly, we find that a preponderance of the evidence supports the
Examiner’s conclusion of obviousness as to claim 1. Claims 3—6, 8—10, and
16 were not argued separately and fall with claim 1.
Dependent Claims
Appellants argue that the Examiner erred in rejecting dependent
claims 11, 13—15, and 17 “by casually throwing in general statements,” that
the Examiner “did not even explain why the method claims 18-21 are
obvious,” and that the Examiner failed “to show prima facie obviousness of
these dependent claims through making the above general statements and
assertions.” (Appeal Br. 23.)
We are not persuaded. Claim 18, which we select as representative
because the claims were not argued separately, recites “[t]he method of
claim 6, wherein the pharmaceutical composition is a pharmaceutical dosage
form suitable for an oral, intravenous, or vaginal delivery system.” (Appeal
Br. 34.) However, the Examiner cites Giiven for teaching “intravenous
administration of omidazole” and Weitgasser for teaching “administration of
omidazole orally and locally (vaginally).” (Final Act. 4.) Thus, we find that
Appellants were on notice of the Examiner’s basis for rejecting claim 18
(thereby establishing a prima facie case of obviousness), and that Appellants
failed to provide persuasive evidence or arguments in response thereto. See
In re Jung, 637 F.3d 1356, 1362-63 (Fed. Cir. 2011).
Accordingly, for the reasons of record and as set forth above, we
affirm the rejection of claim 18. Claims 11, 13—15, 17, and 19—21 were not
18
Appeal 2016-001378
Application 13/831,706
argued separately and fall with claim 18.23 See 37 C.F.R. § 41.37(c)(l)(iv);
see also In re Lovin, 652 F.3d 1349, 1357 (Fed. Cir. 2011).
Conclusion of Law
A preponderance of evidence of record supports the Examiner’s
rejection of claims 1, 3—6, 8—11, and 13—21 under 35 U.S.C. § 103(a).
SUMMARY
We affirm the rejection of all claims on appeal.
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
23 Appellants also argue at length that the Examiner erred in relying on
conclusory statements, which essentially amounts to a list of statements with
which Appellants disagree. (Appeal Br. 25—31.) We discern no reversible
error in the Examiner’s rejection of the claims as obvious.
19