Ex Parte Kopke et al

Patent Trials and Appeals Board

Jul 9, 2019

13391772 - (D) (P.T.A.B. Jul. 9, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
13/391,772 02/22/2012 Richard Dana Kopke
22428 7590 07/11/2019
FOLEY & LARDNER LLP
3000 K STREET N.W.
SUITE 600
WASHINGTON, DC 20007-5109
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
ATTORNEY DOCKET NO. CONFIRMATION NO.
109255-0003 9507
EXAMINER
DRAPER, LESLIE A ROYDS
ART UNIT PAPER NUMBER
1629
NOTIFICATION DATE DELIVERY MODE
07/11/2019 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):
ipdocketing@foley.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte RICHARD DANA KOPKE and ROBERT A. FLOYD
Appeal2018-004305
Application 13/391, 772 1
Technology Center 1600
Before DEMETRA J. MILLS, JEFFREY N. FREDMAN, and
DAVID COTTA, 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 and obviousness-type double patenting. We have
jurisdiction under 35 U.S.C. § 6(b).
We reverse.
1 According to Appellants, the real parties in interest are Hough Ear Institute
and Oklahoma Medical Research Foundation. App. Br. 2.
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Application 13/391,772
STATEMENT OF CASE
The following claim is representative.
30. A method for treating sensorineural hearing loss,
comprising orally delivering to a patient in need thereof a
composition comprising a pharmaceutically effective amount of
2,4-disulfonyl a-phenyl tertiary butyl nitrone.
Cited References
Camey
Kopke '434
Kopke '621
Kopke '595
Kopke
us 5,488,145
US 6,177,434 Bl
US 6,649,621 B2
US 8,420,595 B2
WO 2008/013866 A2
Jan.30, 1996
Jan.23,2001
Nov. 18, 2003
Apr. 16, 2013
Jan. 31, 2008
Erin E. Leary Swan et al., INNER EAR DRUG DELIVERY FOR
AUDITORY APPLICATIONS, 60 Advance Drug Delivery Reviews
1583-99 (2008) (hereinafter "Swan").
Juha Kuokkanen et al., EFFICIENCY OF HYPERBARIC OXYGEN
THERAPY IN EXPERIMENT AL ACUTE ACOUSTIC TRAUMA FROM
FIREARMS, 543 Acta Otolaryngol 132-34 (2000) (hereinafter
"Kuokkanen").
Marie-Pierre Dehouck et al., IN VITRO BLOOD-BRAIN BARRIER
PERMEABILITY AND CEREBRAL ENDOTHELIAL CELL UPTAKE OF
THE NEUROPROTECTIVE NITRONE COMPOUND NXY-059 IN
NORMOXIC, HYPOXIC AND ISCHEMIC CONDITIONS, 955 Brain
Research 229-35 (2002) (hereinafter "Dehouck").
Helen E. Williams et al., INVESTIGATING THE FREE RADICAL
TRAPPING ABILITY OFNXY-059, S-PBN AND PBN, 41 Free
Radical Research 1047-52 (2007) (hereinafter "Williams").
Maples et al., COMPARISON OF THE TRADICAL TRAPPING
ABILITY OF PBN, S-PBN AND NXY-059, Free Radical Research,
34:417-426 (2001 ), (Exhibit 1 to Floyd Declaration; currently
attached as Exhibit B).
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Grounds of Rejection
1. Claims 5-7, 21, 22, 25-28, and 30 are rejected under pre-AIA 35
U.S.C. §103(a) as being unpatentable over Kopke in view of
Williams, Dehouck, Kuokkanen, and Swan.
2. Claims 5-7, 21, 22, 25-28, and 30 are rejected on the ground of
nonstatutory double patenting as being unpatentable over claims
1--4, 6, 8, 11, and 12 ofU.S. Patent No. 5,488,145 in view of
Kopke, Williams, Dehouck, Kuokkanen, and Swan.
3. Claims 5-7, 21, 22, 25-28, and 30 are rejected on the ground of
nonstatutory double patenting as being unpatentable over claims
1, 2, 5, 6, and 9 of U.S. Patent No. 6,177,434 or claims 6 and 8 of
U.S. Patent No. 6,649,621, each alternatively taken in view of
Kopke, Williams, Dehouck, Kuokkanen, and Swan.
4. Claims 5-7, 21, 22, 25-28, and 30 are rejected on the ground of
nonstatutory double patenting as being unpatentable over claims
1-23 and 31-34 of U.S. Patent No. 8,420,595 in view of Kopke,
Williams, Dehouck, Kuokkanen, and Swan.
FINDINGS OF FACT
The Examiner's findings of fact are set forth in the Answer at pages
3-22. The following facts are highlighted.
1. Kopke teaches treating sensorineural hearing loss arising from
acute acoustic trauma (AAT) by administering a
pharmaceutically effective amount of a composition selected
from the group consisting of 4-hydroxy-a-phenyl butyl nitrone
(4-0HPBN), derivatives of 4-0HPBN, and phenyl-N-tert-butyl
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nitrone (PBN) to an organism in which AAT has been induced
(para. 4, 6, and 10). Ans. 4.
2. Kopke states that 4-0HPBN is a free radical trap and
antioxidant. Kopke 3.
3. Williams teaches that the nitrone compounds 2,4-
disulphophenyl-N-tert-butyl nitrone (NXY-059), 2-
sulphophenyl-N-tert-butyl nitrone (S-PBN) and a-phenyl-N-
tert-butyl nitrone (PBN) function to trap free radicals, and that
NXY-059 traps a greater number of hydroxyl and methanol
radicals than the other two nitrones. Williams Abstract.
4. Dehouck teaches that NXY-059 crosses the blood-brain barrier
(BBB) under conditions of ischemia or hypoxia. Dehouck p.
234, col. 1, first full paragraph; Fig. 2a.
5. Kuokkanen teaches that AA T is characterized by hypoxia in the
inner ear and that the condition is frequently treated by
exposure to a hyperbaric oxygen environment. Kuokkanen
Abstract; p. 133, col. 2.
6. Swan teaches that the inner ear has a blood-cochlear barrier
(BCB) that is similar in structure and function to the BBB.
Swan p. 1584, col. 1; p. 1586, sections 3 .1.1 and 3 .1.2.
7. STN Reg. No. 168021-79-2 is cited solely for its teaching that
NXY-059 is synonymous with Appellants instantly claimed
compound 2,4-DSPBN, as evidenced by their identical
chemical structure. See, e.g., the as-filed Specification at p. 3,
para. 20.
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PRINCIPLES OF LAW
In making our determination, we apply the preponderance of the
evidence standard. See, e.g., Ethicon, Inc. v. Quigg, 849 F.2d 1422, 1427
(Fed. Cir. 1988) (explaining the general evidentiary standard for proceedings
before the Office).
Obviousness Rejection
The Examiner finds that
Kopke et al. teaches treating sensorineural hearing loss
arising from acute acoustic trauma ( AA T) by administering a
pharmaceutically effective amount of a composition selected
from the group consisting of 4-hydroxy-a-phenyl butyl nitrone
(4-0HPBN), derivatives of 4-0HPBN, and phenyl-N-tert-butyl
nitrone (PBN) to an organism in which AAT has been induced
(para.4, 6, and 10).
Ans. 4 ( emphasis omitted). Kopke states that the related compound, phenyl
butyl nitrone, is a free radical trap and antioxidant. Kopke 3. Kopke does
not explicitly teach treating AAT with 2,4-DSPBN. Ans. 4. The Examiner
relies on Williams for the disclosure of the claimed 2,4-disulfonyl a-phenyl
tertiary butyl nitrone (NXY-059) as a free radical trap. Williams Abstract,
Table I.
The Examiner concludes that
A person of ordinary skill in the art at the time the instant
invention was made would have had a reasonable expectation
of success in substituting NXY-059 (i.e., the claimed compound
2,4-DSPBN) for 4-0HPBN in the treatment of AAT-related
hearing loss described by Kopke et al.[,] because Kopke et al.
teaches that AAT-related hearing loss was effectively treated
using nitrone free radical traps to minimize deafness from
oxidative stress; Kuokkanen teaches that AAT is characterized
by hypoxic conditions in the inner ear; Dehouck teaches that
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NXY-059 crosses the BBB[2] under low-oxygen conditions;
and Swan teaches that the BCB of the inner ear operates
similarly to the BBB. The skilled artisan would, therefore,
reasonably have predicted that NXY-059 would cross the
hypoxic BCB inherently present in Kopke's AAT subject,
where it would proceed to trap hydroxyl radicals as discussed
by Williams. The skilled artisan would have been motivated to
substitute NXY-059 for 4-0HPBN because Williams teaches
that NXY-059 was an extremely effective free-radical
scavenger and because Dehouck teaches that it crosses the BBB
(and, given the teachings of Swan, the BBB by extension)
effectively under hypoxic conditions, such as those inherently
present in Kopke's AAT subject, according to Kuokkanen.
Ans. 5.
Appellants contend that, in a Declaration under 37 CPR 1.132, Dr.
Floyd testified that,
it would appear that the Examiner's reliance on the work of
Williams et al. should be given little weight, if any, as the
highly acidic (pH 3 .2 and 1. 8) in vitro conditions utilized by
these authors have very little bearing on what might happen
under practical in vivo conditions, as the authors, themselves,
admit freely.
Floyd Declaration, paragraph 7. Appellants argue that, "[t]he Examiner's
interpretation of Dehouck is ... selective and incomplete." App. Br. 6.
Appellants argue that, "the authors of Dehouck explicitly admitted that
"[t]he results clearly demonstrate that the cell uptake of [2,4-DSPBN] is
negligible in normoxic, hypoxic or ischemic conditions in vitro." App. Br. 7
( emphasis omitted).
2 Blood brain barrier.
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Appellants argue that the person of ordinary skill in the art would
lack sufficient motivation to choose 2,4-DSPBN over PBN for free radical
trapping in the inner ear region. App. Br. 8. Appellants argue that
the likelihood of PBN entering blood circulation after oral
administration is nearly two orders of magnitude higher than
that of 2,4-DSPBN .... Accordingly, one of ordinary skill in
the art would have expected much more PBN than 2,4-DSPBN
to be available for free radical trapping in the inner ear region
(i.e., 85x20=1,700 times more), when the same amounts of
PBN and 2,4-DSPBN are administered orally.
App. Br. 8.
Finally, Appellants argue that "[t]he claimed oral administration of
2,4-DSPBN leads to unexpected success in treating sensorineural hearing
loss." App. Br. 11.
ANALYSIS
We find that the Examiner has provided evidence to support a prima
facie case of obviousness, but that Appellants' rebuttal evidence relating to a
reasonable expectation of success, has overcome the Examiner's prima facie
case.
With respect to the Examiner's prima facie case of obviousness,
Kopke teaches a PBN compound (which is structurally related to the claimed
2,4-DSPBN), for the treatment of AAT which is a free radical trap with
antioxidant properties. Williams teaches the claimed 2,4-DSPBN is also a
free radical trap. According to Kopke, "[t]hese compounds preclude the
generation of intracellular reactive oxygen species (ROS) which leads to
oxidative stress and damage of the mitochondria. Oxidative damage of the
mitochondria is known to cause apoptosis and necrosis leading to cell
death." Kopke 3. Williams disclosed that, "results obtained showed that
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NXY-059 trapped a greater number of hydroxyl and methanol radicals than
the other two nitrones" (PBN, S-PBN), which are the cause of hearing loss.
Williams Abstract.
Thus, based on the cited references, one of ordinary skill in the art
would have been prima facie motivated to substitute the better free radical
trap, 2,4-DSPBN, for PBN in a method of treatment of AAT, because free
radicals are indicated to be a cause of hearing loss. The Examiner further
established that one of ordinary skill in the art would have reasonably
expected 2,4-DSPBN to cross the BBB under hypoxic conditions, albeit at a
rate significantly less than that of PBN. A reference may be relied upon for
all that it would have reasonably suggested to one having ordinary skill the
art, including non-preferred embodiments. Merck & Co. v. Biocraft Labs.,
874 F.2d 804, 807 (Fed. Cir. 1989). In addition, Camey (Ans. 19, and of
record) discloses successful in vivo administration of the claimed 2,4-
DSPBN compound for treating central nervous system oxidation. Abstract.
Camey suggests that this compound be administered orally, and is more
effective in treating neuronal loss, in vivo, than PBN. Abstract, Example 5,
col. 12.
In the present case, structurally related free radical traps were known
in the art for the treatment of nervous system oxidation, including AA T, and
it would have been prima facie obvious to one of ordinary skill in the art to
select from available free radical traps that were structurally related to PBN
for the treatment of AAT with some expectation of success.
Appellant bears the burden of providing factual evidence of non-
obviousness to rebut the Examiner's primafacie case. Ex parte Phillips, 28
USPQ2d 1302 (BPAI 1993). "Rebuttal is merely 'a showing of facts
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supporting the opposite conclusion,' and may relate to any of the Graham
factors including so-called secondary considerations. If rebuttal evidence
of adequate weight is produced, the holding of prima facie obviousness,
being but a legal inference from previously uncontradicted evidence, is
dissipated." In re Piasecki, 745 F.2d 1468, 1472 (Fed. Cir. 1984). Bold
emphasis added.
In the present case, Appellants have provided adequate evidence of
lack of expectation of success at the time of the invention to rebut the
Examiner's prima facie case of obviousness. A preponderance of the
evidence supports Appellants' position with respect to lack of expectation of
success. We have carefully considered all Declarations of record, with
emphasis on the Floyd and Kopke Declarations.
In particular, the Floyd Declaration, paragraph 11, evidences the
failure of PBN to treat acoustic trauma. The Declaration states that,
"PBN administration appeared to reduce auditory
impairment in animals exposed to noise alone, but the
difference was not found to be statistically significant." (See,
Rao et al., Toxicology and Applied Pharmacology) 2000. 167:
125-131, attached as Exhibit 2.) (See, also, Fetcher et al., JARD
2004. 5:90-98. attached as Exhibit 3: "However PBN at the
dose and time interval given was ineffective in protecting
auditory function in subjects exposed to noise alone.")
Floyd Declaration ,r 11. Therefore, we agree with Appellants that one of
ordinary skill in the art, (understanding that the compound (PBN), a
structurally related spin trap compound to the claimed 2,4-DSPBN
compound, was ineffective in providing a statistically significant, protective
effect in treating acoustic trauma), would not have been provided with an
expectation of success that the claimed 2,4-DSPBN compound would have
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been effective in treating acoustic trauma. The above facts, combined with
the fact that Dehouk teaches that 2,4-DSPBN has negligible ability to cross
the BBB (Floyd Declaration ,r 9); and that 2,4-DSPBN has very poor
bioavailability upon oral administration (Floyd Declaration ,r 13, and App.
Br. Exhibit I); would not have provided one of ordinary skill in the art, at the
time of the invention, with a reasonable expectation of success that the 2,4-
DSPBN compound would have been effective to treat acoustic trauma.
In sum, Appellants have provided convincing evidence to rebut the
Examiner's prima facie case of obviousness by showing a lack of a
reasonable expectation of success, and the obviousness rejection is reversed.
Double Patenting Rejections
With respect to each of the obviousness-type double patenting
rejections, Appellants argue that the cited patents and additional cited
references fail to teach anything about treating sensorineural hearing loss
using 2,4-DSPBN. App. Br. 20.
Appellants further argue that
none of Kopke, Williams, Dehouck, Kuokkanen, and Swan,
alone or in combination, would have provided sufficient
guidance for one of ordinary skill in the art to arrive at the
present invention. And the fact that 2,4-DSPBN succeeded in
treating sensorineural loss, while PBN - which has nearly two
orders of magnitude higher oral bioavailability than 2,4-
DSPBN, has at least 20 times higher permeability across BBB
than 2,4-DSPBN, and is a better free radical trapping agent than
2,4-DSPBN at physiological condition- failed to treat the same
indication, also teaches away from treating sensorineural
hearing loss using 2,4-DSPBN. Nothing in the cited claims of
US 5,488,145, US 6,177,434, US 6,649,621 and US 8,420,595
could have bridged the gap between the present invention and
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the prior art such as Kopke, Williams, Dehouck, Kuokkanen,
and Swan.
App. Br. 20.
ANALYSIS
Obviousness-type double patenting entails a two-step analysis. First,
the allegedly conflicting claims are construed and, second, the difference(s)
between the claims are considered to determine whether the claims are
patentably distinct. See Eli Lilly & Co. v. Barr Labs., Inc., 251 F.3d 955,
968, 58 USPQ2d 1869, 1878 (Fed. Cir. 2001). "A later patent claim is not
patentably distinct from an earlier patent claim if the later claim is obvious
over, or anticipated by, the earlier claim." Id.
We preliminarily note that there does not appear to be application
continuity, or restriction requirement between any of the cited patents and
the present patent application.
Obviousness-type Double Patenting Rejection 1
Claims 5-7, 21, 22, 25-28, and 30 are rejected on the ground of
nonstatutory double patenting as being unpatentable over claims 1--4, 6, 8,
11, and 12 of U.S. Patent No. 5,488,145 ('145) in view of Kopke, Williams,
Dehouck, Kuokkanen, and Swan.
Claim 1 of the '145 patent reads:
1. 2,4-disulfonyl o-phenyl tertiary butyl nitrone.
In contrast, pending claim 30 is directed to "[a] method for treating
sensorineural hearing loss, comprising orally delivering to a patient in need
thereof a composition comprising a pharmaceutically effective amount of
2,4-disulfonyl a-phenyl tertiary butyl nitrone."
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Because the pending claims are directed to a method and the claims of
the '145 patent are directed to a compound with no specified medical
application, we reverse the obviousness-type double patenting rejection. We
find that the Examiner has not shown why one of ordinary skill in the art
would have selected, or have been provided with an expectation of success,
that the claimed 2,4 DSPBN compound would successfully treat
sensorineural hearing loss, for the same reasons indicated for the
obviousness rejection discussed above. Appellants' rebuttal evidence with
respect to a reasonable expectation of success is convincing over the claims
of the '145 patent combined with the disclosures of Kopke, Williams,
Dehouck, Kuokkanen, and Swan.
The claims of the pending application are not obvious over, or
anticipated by, the earlier cited claims of the' 145 patent. The obviousness-
type double patenting rejection over '145 patent is reversed.
Obviousness-type Double Patenting Rejection 2
Claims 5-7, 21, 22, 25-28, and 30 are rejected on the ground of
nonstatutory double patenting as being unpatentable over claims 1, 2, 5, 6,
and 9 of U.S. Patent No. 6,177,434 or claims 6 and 8 of U.S. Patent No.
6,649,621, each alternatively taken in view of Kopke, Williams, Dehouck,
Kuokkanen, and Swan.
Claim 1 of the '434 patent reads as follows:
1. A method of reducing, restoring, or protecting a subject against
hearing loss by administering to a subject a pharmaceutically effective
amount of antioxidant compounds.
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2. The method of claim 1 wherein the compound is selected from the
group consisting of R-PIA, L-NAC, and glutathione monoethyl ester.
Claim 6 of the '621 patent reads as follows:
6. A method for preventing and treating sensorineural hearing loss,
comprising: ( c) selecting subjects experiencing said hearing loss or at risk
for acute exposure to noise, toxins, or other stressors causing said hearing
loss, and
( d) administering to said subjects a pharmaceutically effective amount
of a mixture of compounds selected from the group consisting of:
N-L-acety lcysteine;
an ester of salicylic acid;
a salt of salicylic acid; and
any combination thereof.
In contrast, pending claim 30 is directed to "A method for treating
sensorineural hearing loss, comprising orally delivering to a patient in need
thereof a composition comprising a pharmaceutically effective amount of
2,4-disulfonyl a-phenyl tertiary butyl nitrone."
We find that the Examiner has not shown why one of ordinary skill in
the art would have selected and been provided with a reasonable expectation
of success, that the claimed 2,4 DSPBN compound could be used for the
treatment of sensorineural hearing loss in combination with additional
antioxidants, for the same reasons indicated for the obviousness rejection
discussed above. Appellants' rebuttal evidence with respect to a reasonable
expectation of success is convincing over the cited claims of the '434 and
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'621 patents combined with the disclosures of Kopke, Williams, Dehouck,
Kuokkanen, and Swan.
The obviousness-type double patenting rejection over '434 and '621
patents is reversed.
Obviousness-type Double Patenting Rejection 3
Claims 5-7, 21, 22, 25-28, and 30 are rejected on the ground of
nonstatutory double patenting as being unpatentable over claims 1-23 and
31-34 of U.S. Patent No. 8,420,595 in view of Kopke, Williams, Dehouck,
Kuokkanen, and Swan.
Claim 1 of the '595 patent reads:
1. A method for treating sensorineural hearing loss comprising:
delivering to an organism which has experienced sensorineural hearing loss
a pharmaceutically effective amount of a composition comprising 4-
hydroxy-0-phenylbutyl nitrone.
To begin, claim 1 of the '595 patent is directed to 4-hydroxy-0-
phenylbutyl nitrone, a different compound than the claimed 2,4-DSPBN.
We find that the Examiner has not explained or shown why one of ordinary
skill in the art would have selected the claimed 2,4 DSPBN compound for
the treatment of sensorineural hearing loss, for the same reasons indicated
for the obviousness rejection discussed above. Appellants' rebuttal evidence
with respect to a reasonable expectation of success is convincing over the
cited claims of the '595 patent combined with the disclosures of Kopke,
Williams, Dehouck, Kuokkanen, and Swan.
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The claims of the pending application are not obvious over, or
anticipated by, the earlier cited claims of the '595 patent. The obviousness-
type double patenting rejection over '595 patent is reversed.
CONCLUSION OF LAW
The obviousness rejection and obviousness-type double patenting
rejections are reversed.
REVERSED
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