Thomas Meyer

Patent Trials and Appeals Board

Apr 20, 2020

14694122 - (D) (P.T.A.B. Apr. 20, 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.
14/694,122 04/23/2015 Thomas MEYER AURS-003/01US
320461-2019
1853
58249 7590 04/20/2020
COOLEY LLP
ATTN: IP Docketing Department
1299 Pennsylvania Avenue, NW
Suite 700
Washington, DC 20004
EXAMINER
STEELE, AMBER D
ART UNIT PAPER NUMBER
1658
NOTIFICATION DATE DELIVERY MODE
04/20/2020 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):
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PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte THOMAS MEYER
____________

Appeal 2018-006386
Application 14/694,122
Technology Center 1600
____________

Before DONALD E. ADAMS, ROBERT A. POLLOCK, and
MICHAEL A. VALEK, Administrative Patent Judges.

VALEK, Administrative Patent Judge.

DECISION ON APPEAL
Appellant1 submits this appeal under 35 U.S.C. § 134(a) involving
claims to a method of ameliorating or reducing the occurrence of acute inner
ear tinnitus induced by a cochlear insult. We have jurisdiction under
35 U.S.C. § 6(b).
We REVERSE.

1 We use the word “Appellant” to refer to “applicant” as defined in
37 C.F.R. § 1.42. Appellant identifies Auris Medical AG as the real party in
interest. Appeal Br. 3. Herein, we refer to Examiner’s office action mailed
January 27, 2017 (“Final Act.”), Appellant’s Appeal Brief filed November
22, 2017 (“Appeal Br.”), and Examiner’s Answer mailed March 30, 2018
(“Ans.”).
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STATEMENT OF THE CASE
According to the Specification, “[t]innitus, the perception of sound
without external acoustic stimulation, is a very common disorder.” Spec. ¶
3. However, “there exists no universal standard of care for tinnitus or
approved tinnitus drug, provoking substantial frustration among patients and
physicians.” Id. ¶ 4 (citations omitted). The Specification explains that
“[t]he present invention is based, in part, on the discovery that inhibition of
c-Jun N terminal kinase (JNK) in cells of the cochlea reduces the loudness of
tinnitus and leads to more frequent occurrences of complete remission of the
tinnitus, particularly in patients having severe hearing loss.” Id. ¶ 9.
Claims 1–22 are on appeal and can be found in the Claims Appendix
of the Appeal Brief. Appeal Br. 3. Claim 1 is representative and reads as
follows:
1. A method of ameliorating or reducing the occurrence of
acute inner ear tinnitus induced by a cochlear insult in a human
in need thereof comprising administering to the human a
pharmaceutical composition comprising a therapeutically
effective amount of a peptide inhibitor of c-Jun N-terminal
kinase (JNK) or a pharmaceutically acceptable salt thereof,
wherein the peptide inhibitor is no more than 50 amino acids in
length and comprises a sequence that is at least 80% identical to
the sequence of any one of SEQ ID NOs: 1 to 4 and 13 to 45.
Id. at 26. Appellant seeks review of Examiner’s rejection of claims 1–22
under 35 U.S.C. § 103 as obvious over Bonny2 and Crummer.3 See id. at

2 US 2007/0060514 A1, published Mar. 15, 2007 (“Bonny”).
3 Richard W. Crummer et al., Diagnostic Approach to Tinnitus, 69 Am.
Family Physician, 120–26 (2004) (“Crummer”).
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The issue before us is whether a preponderance of the evidence
supports Examiner’s conclusion that Appellant’s claims are obvious over the
cited prior art.
Analysis
Examiner finds that Bonny teaches that peptide JNK inhibitors having
sequences identical to Appellant’s SEQ IN NO: 1 and 2 are effective “for the
prevention of hearing loss following noise trauma.” Final Act. 2. Examiner
acknowledges that “Bonny does not show a direct correlation to the
treatment of tinnitus with treatments recommended for treating hearing
loss,” but finds that Crummer “show[s] noise-induced hearing loss to be the
most common cause of tinnitus.” Id. at 3 (citing Crummer, Abstr.).
Examiner concludes “it would have therefore been obvious to one of
ordinary skill in the art that treatment of hearing loss according to known
methods [in Bonny] would additionally treat associated tinnitus.” Id.
Appellant argues that Examiner has failed to establish a prima facie
case because Crummer read “as a whole” teaches that “hearing loss and
tinnitus are two different symptoms, which are often (but not necessarily)
caused by the same conditions.” Appeal Br. 9. In particular, Appellant cites
evidence that “the mechanisms behind the two may be different.” Id. at 9
(citing Canlon,4 2). Thus, Appellant urges that one of ordinary skill in the
art would not be motivated to combine Bonny and Crummer as articulated in
the rejection and, even if they were, there would no reasonable expectation
that “a drug capable of treating hearing loss was also capable of treating
tinnitus.” See Id. at 10–13.

4 Barbara Canlon, Pharmacological Strategies for Prevention and Treatment
of Hearing Loss and Tinnitus, 226 Hearing Res., 1–2 (2007).
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While Appellant’s arguments are not without merit, we determine that
Examiner has met the initial burden to establish a prima facie case of
obviousness. Crummer teaches, and Appellant does not dispute, that in most
instances hearing loss and tinnitus are closely associated with each other.
See Crummer, 121 (“Most cases of tinnitus result from the same conditions
that cause hearing loss.”); Appeal Br. 10 (“To be clear, Appellant does not
mean to deny the fact that tinnitus and hearing loss are often observed
together in many patients having otologic disorders.”). Thus, the record
supports Examiner’s determination (see Final Act. 3–5) that a skilled artisan
would be motivated administer Bonny’s peptide JNK inhibitor to patients
exhibiting tinnitus and would have a reasonable expectation that the
compound known to be effective for one symptom (hearing loss) would also
be effective for tinnitus at least where both symptoms resulted from the
same underlying condition.
We reach a different conclusion with respect to Appellant’s rebuttal
evidence, which we agree is sufficient to outweigh Examiner’s prima facie
showing. Appellant cites evidence of multiple examples in which
compounds known to treat hearing loss were not effective for tinnitus. See
Appeal Br. 14–16 (citing references). In particular, Appellant cites Guitton5
as evidence that “a person of ordinary skill in the art would have understood
that a JNK inhibitor . . . can treat hearing loss, but cannot treat tinnitus” and
thus that the data in the Specification is an unexpected result. Id. at 17–24.
Guitton describes results from testing of “D-JNKI-1, a peptide
inhibitor of c-Jun N-Terminal kinase” known to “protect against auditory

5 US 2005/0214338 A1, published Sept. 29, 2005 (“Guitoon”).
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hair cell death and hearing loss due to acoustic trauma” in an animal model
for tinnitus. Guitton ¶ 40. In Guitton’s model, rats were conditioned to
respond to sound, subjected to traumatizing sound, and then observed to
assess “false positives,” i.e., performance of the conditioned behavior
“without [] acoustic simulation, i.e., during periods of silence,” which “can
be interpreted as the perception of tinnitus.” Id. ¶ 48. Based on these
observations, the rats were divided into groups with “some animals
exhibiting no tinnitus at all (group 1), some only in a transitory form (group
2), and some first in a transitory form, and then permanently again for the
rest of the observation period.” Id. ¶ 59. The data for the animals
administered D-JNKI-1 show a similar number of false positives as animals
that did not receive D-JNKI-1 for all three groups. Compare Id. Fig. 3B
(false positives for animals receiving D-JNKI-1) to Fig. 2B (false positives
for control group). From this data, Guitton concludes that “[w]hile D-JNKI-
1 prevented permanent hearing loss after acute acoustic trauma, it had no
significant effect on the number of false positives and thus the prevention of
tinnitus.” Id. ¶ 62; see also ¶ 20 (describing Fig. 3).
The data in Appellant’s Specification show a very different result.
The Specification reports data from a phase IIb study with 188 patients in
the analysis set. Spec. ¶ 56. According to Appellant’s data, “a statistically
significantly higher percentage of subjects” in the “‘severe to profound
hearing loss’ subgroup,” who received the peptide JNK inhibitor AM-1116
“achieved complete tinnitus remission over the 90 days as compared with

6 AM-111 is the peptide of “SEQ ID NO:2 in which all chiral amino acids
are in the D configuration and the peptide is synthesized in the reverse
order.” Spec. ¶ 48.
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placebo (56.0% vs. 26.1%, p=0.045).” Id. ¶ 60 (Table 3). Thus, at least for
this subgroup of patients, the data in the Specification evidence the opposite
of the result that would be expected from the data in Guitton.
Examiner does not disagree that the results in the Specification would
have been unexpected in light of the teaching in Guitton, but takes issue with
the design of Guitton’s animal model.7 According to Examiner,
Guitton et al. (Exhibit K) teach various drawbacks of the animal
model utilized (see paragraph 39.) Guitton et al. teach very
small numbers of animals in the studies (e.g., 4–6; paragraph
64) which would not equate to the discussion in paragraph 39
which states that more animals are required for better results.
Ans. 13.
Appellant disagrees with Examiner’s interpretation, arguing that that
paragraph 39 of Guitton “provides a summary of factors that were
considered when Guitton et al. designed the experiment.” Appeal Br. 19.
According to Appellant, “the experiment in Guitton et al. had a reasonable
design for quality control in view of the considerations in paragraph [0039].”
Id.
We determine that Appellant has the better position. Guitton
paragraph 39 explains that because “tinnitus in general is not directly

7 In the Answer, Examiner additionally asserts that JNK inhibitors, such as
D-JNKI-1 and the others recited in claim 1, were known to “alter NMDA-
mediated signal transduction.” Ans. 14. Thus, Examiner suggests a skilled
artisan would have expected JNK inhibitors to be effective for tinnitus
because Guitton “found that permanent tinnitus was absent with treatment of
7-CK or ketamine – NMDA antagonists.” Id. Given the data in Figures 2
and 3 and Guitton’s express teaching that D-JNKI-1 “had no significant
effect on the prevention of tinnitus,” (Guitton ¶ 20) we are not persuaded
that one of ordinary skill in the art would read the reference as Examiner
suggests.
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observable . . . the definition an implementation of such an animal model
represented a substantial challenge.” Guitton ¶ 39. However, the same
paragraph indicates that the authors overcame that challenge and
successfully “developed and tested” such a model. Id. Indeed, Guitton
describes at great length the methods employed to develop and validate its
animal model. See id. ¶¶ 40–54. Based on the record before us, we see no
reason to question the validity of the experiment, data, and conclusions
reported in Guitton. See In re Soni, 54 F.3d 746, 751 (Fed. Cir. 1995)
(“[W]hen an applicant demonstrates substantially improved results . . . and
states that the results were unexpected, this should suffice to establish
unexpected results in the absence of evidence to the contrary.”).
For these reasons and on this record, we agree with Appellant that the
results evidenced by the Specification are unexpected, particularly in light of
of the teachings in Guitton concerning D-JNKI-1. Considering “the entire
merits of the matter” in light of this evidence, we determine that Appellant’s
rebuttal evidence outweighs Examiner’s prima facie case and therefore that a
preponderance of the evidence does not support the rejection. See In re
Hedges, 783 F.2d 1038, 1039 (Fed. Cir. 1986). Accordingly, we reverse.

CONCLUSION
In summary:
Claims
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
1–22 103 Bonney, Crummer 1–22

REVERSED