Ex Parte Slomianny

Patent Trials and Appeals Board

Apr 25, 2019

14167676 - (D) (P.T.A.B. Apr. 25, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
14/167,676 01/29/2014 Jan Slomianny
62836 7590 04/29/2019
Brooks Kushman P.C. / BERLINER & ASSOCIATES
1000 Town Center, 22nd Floor
22nd Floor
Southfield, MI 48075
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.
HSJSOlOlPUSAl 4346
EXAMINER
DRAPER, LESLIE A ROYDS
ART UNIT PAPER NUMBER
1629
NOTIFICATION DATE DELIVERY MODE
04/29/2019 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):
docketing@brookskushman.com
nwhitlock@brookskushman.com
lwerk@brookskushman.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte JAN SLOMIANNY
Appeal2018-008136
Application 14/167,676
Technology Center 1600
Before JEFFREY N. FREDMAN, DEBORAH KATZ, and
JOHN G. NEW, Administrative Patent Judges.
FREDMAN, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal 1,2 under 35 U.S.C. § 134(a) involving claims to a
method of treatment of a virus infection. The Examiner rejected the claims
as lacking written description and enablement. We have jurisdiction under
35 U.S.C. § 6(b). We AFFIRM.
1 Appellant identifies the Real Party in Interest as Jan Slomianny (see App.
Br. 3).
2 We have considered and herein refer to the Specification of Jan. 29, 2014
("Spec."); Final Office Action of Jan. 11, 2017 ("Final Act."); Appeal Brief
of Feb. 9, 2018 ("App. Br."); and Examiner's Answer of Apr. 25, 2018
("Ans.").
Appeal2018-008136
Application 14/167,676
Statement of the Case
Background
"The treatment of virus infections in humans and animals has always
been a great challenge due to the fact that only a limited number of active
agents is available and this is also true for the family of herpesviruses"
(Spec. 1 :4--6). "Various agents were developed against herpesviruses but
these are mainly effective in that they alleviate the symptoms and generally
have merely a limited influence on the course of the disease" (Spec. 1 :21-
23). "Surprisingly, it has now been found that an active agent, piroxicam,
which belongs to the group ofNSAIDs is suited for the prophylactic and
therapeutic treatment of virus infections" (Spec. 2: 15-1 7).
The Claims
Claims 1--4, 8, and 9 are on appeal. Independent claim 1 is
representative and reads as follows:
1. A method of treatment of a virus infection caused by a virus
of the family of herpesviridae, the method comprising
administering to a patient in need of such treatment an
agent in an amount effective to treat the virus infection, wherein
the agent contains piroxicam in a carrier substance, the
piroxicam being in an amount effective to provide virucidal
activity against the virus,
wherein the administering is by topical administration,
and the agent is in the form of a cream, ointment, tincture or
gel.
2
Appeal2018-008136
Application 14/167,676
The Issues
A. The Examiner has rejected claims 1--4, 8, and 9 under 35 U.S.C. §
112(pre-AIA), first paragraph, as failing to comply with the
enablement requirement (Ans. 6-10).
B. The Examiner has rejected claims 1--4, 8, and 9 under 35 U.S.C.
§ 112(pre-AIA), first paragraph, as failing to comply with the written
description requirement (Ans. 3---6).
A. 35 U.S. C. § 112, first paragraph, enablement
The Examiner determines the claims "assert that the administration of
piroxicam in any amount that exhibits virucidal activity against any ( or all)
viruses of the herpesviridae family to a patient infected with the same will
treat the infection by deactivating or destroying the virus (i.e., 'virucidal
activity')" (Ans. 8). The Examiner finds that at the time the invention was
filed, "piroxicam was known to play an established role in analgesia and
reduction of inflammation when administered and the art was generally
unaware of any or all amounts of piroxicam that would exhibit virucidal
activity against any or all types of viruses caused by herpesviridae" (id.).
The Examiner finds it would require undue experimentation for the person
of ordinary skill in the art "to identify the full scope of amounts of piroxicam
that exhibit virucidal activity against all types of herpes virus" (see Ans. 9).
The Examiner finds "the working examples provided in the as-filed
specification do not remedy this lack of adequate enabling guidance" (Ans.
9). More specifically, the Examiner finds Appellant's "nebulous reference
3
Appeal2018-008136
Application 14/167,676
to 'signs of amelioration' provides no basis to assume that the amelioration
was, in fact, virucidal in nature" in Test Report 1 (id.). The Examiner finds:
'Test Report 2' demonstrates the in vitro virucidal activity of 'a
piroxicam-containing gel with an active content of 0.4%'
against cell cultures infected with HSVl, but fails to describe
the actual amount of piroxicam used or any in vivo virucidal
activity of piroxicam against HSVl (let alone any or all other
herpes viruses) in a patient infected with the same
(id.). The Examiner concludes:
(id.).
While the lack of adequate working examples cannot be the
sole factor in determining enablement, the unpredictable nature
of the art and the absence of substantial evidence commensurate
in scope with the breadth of the presently claimed subject
matter provides additional weight to the present conclusion of
insufficient enablement in consideration of the Wands factors as
a whole
The issue with respect to this rejection is: Does the evidence of record
support the Examiner's conclusion that the Specification does not enable the
full scope of the claimed invention?
Findings of Fact ("FF'')
Breadth of the Claims
1. Claim 1 broadly encompasses treating a virus infection caused
by a virus of the family of Herpesviridae by topically administering
piroxicam in an amount effective to provide virucidal activity against the
virus (see Claim 1 ).
2. Claim 4 requires a virus infection caused by herpes simplex
(App. Br. 15).
4
Appeal2018-008136
Application 14/167,676
3. Claim 8 requires a virus infection caused by herpes labialis
(App. Br. 15).
4. Claim 9 requires a virus infection caused by varicella zoster
virus (App. Br. 16).
Nature of the Invention
5. The Specification teaches:
The family of Herpesviridae comprises a great number of
viruses having a double-stranded DNA. Widely spread are
herpes simplex viruses of type HSV 1 and HSV 2 as well as the
herpes varicella zoster virus VZV. All cause painful infections
in the form of superficial inflammation. Herpesviruses remain
dormant within the human body for a long time so that the
outbreaks of the disease will occur repeatedly and may even
display serious symptoms.
(Spec. 1:7-12).
Presence of Working Examples
6. The Specification teaches a working example of treating human
subjects in Test Report 1 as follows:
Making use of a commercially available piroxicam gel with an
active agent content of 0.5 % w/w the inventive agent was
tested on 42 subjects with results achieved as follows:
Of the 42 test persons 26 used the agent once and 16 subjects
used it up to five times.
15 of the 42 subjects noted signs of amelioration in less than
one day ( which also included that outbreaks of the disease
could be prevented), 21 subjects reported amelioration in one to
three days and two an amelioration in four to ten days.
Tolerability of the agent was reported by 41 of the test persons
as good and one subject stated tolerability to be not so good.
One subject reported the agent had not helped.
5
Appeal2018-008136
Application 14/167,676
(Spec. 3: 18--4:3).
7. The Specification teaches an in vitro working example in Test
Report 2 as follows:
In a screening test a piroxicam-containing gel with an active
agent content of 0.4 % was tested on cultures infected by
herpesviruses of type HSVl adopting standard testing methods.
Initially, the CDso-value was found to be 2.50, with the virus
titer being 7 .00 in the beginning. After a residence time of 1, 5
and 60 min. the virus titer (log10 TCIDso/ml) was found to be
lower than 2.50 corresponding to a reduction of the virus count
by more than 99 .99 %.
(Spec. 4:14--19).
Amount of Direction or Guidance Presented
8. The Specification teaches "the agent preferably contains
piroxicam in an amount of 0.1 to 10% w/w, preferably 0.1 to 5 and
especially preferred in an amount ranging between 0.5 and 5% w/w. It may
be administering topically, orally or parenterally" (Spec. 2:25-28).
9. The Specification teaches the "agent is preferably employed for
the treatment of infections in the region of the mouth, commonly known by
the term herpes labialis. These are infections resulting from the herpes
simplex virus HSV 1 or HSV 2, with the agent also being effective against
herpes zoster VZV" (Spec. 3:1--4).
10. The Specification teaches "[t]he agent is used by patients 1 to 5
times, 1 to 2 times daily. The majority of the patients said that a single use
of the agent had been successful" (Spec. 3: 12-13).
State of the Prior Art and Unpredictability of the Art
11. The Specification teaches EP 1457202 A2 describes the use of
"non-steroidal anti-inflammatory drugs (NSAIDs) for the treatment of
6
Appeal2018-008136
Application 14/167,676
herpes infections," where "healing of lesions appeared to take five days on
average" thus shortening the normal infection duration of up to 10 days
(Spec. 2:5-14).
12. Lee 3 teaches:
The herpesviruses comprise a large family of double stranded
DNA viruses. The herpesvirus family can be divided into three
subfamilies (i.e., a, B, and y) based upon a number of biological
properties such as host range and tropism, viral life cycle, and
viral persistence and latency. Eight of the herpesviruses, herpes
simplex virus types 1 and 2 (HSV-1 and HSV-2), varicella
zoster virus (VZV), human cytomegalovirus (HCMV), Epstein-
Barr virus (EBV), and human herpes viruses 6, 7, and 8 (HHV-
6, HHV-7, and HHV-8), have been shown to infect humans.
(Lee ,r 12).
13. Lee teaches "[t]here is no treatment known to kill the herpes
virus at this time. Most of the available treatments can only help to
accelerate the healing of the lesions and the associated symptoms, but have
not been shown to be efficacious in the treatment of herpes virus infections"
(Lee ,r 16).
14. Lee teaches "NSAIDs are not widely known for treatment of
viruses, notwithstanding herpes viruses" (Lee ,r 19).
15. Lee teaches a method for treating patients with pain and/ or
inflammation associated with infection caused by herpes simplex virus
and/or varicella-zoster virus by topically applying an effective amount of
diclofenac. Optionally, diclofenac may be replaced with an NSAID, e.g.,
piroxicam (Lee ,r,r 26-27).
3 Lee et al., US 2004/018006 Al, published Sept. 16, 2004.
7
Appeal2018-008136
Application 14/167,676
16. De Benedittis4 teaches treating acute herpetic neuralgia and
post-herpetic neuralgia with piroxicam (20 mg) in ethyl ether solution
resulting in analgesic activity (see De Benedittis 3:54--59).
17. Nicholls5 teaches treating post-herpetic neuralgia following
Herpes zoster infection by topically applying 0.5% piroxicam gel (see
Nicholls 233).
Skill in the Art
18. The Examiner and Appellant agrees that the level of skill in the
art is high (Ans. 1 O; App. Br. 9).
Predictability
19. Appellant states "[ t ]he claims are biological and medical in
nature, which are considered of low predictability" (App. Br. 9).
Principles of Law
When rejecting a claim under the enablement requirement of
section 112, the PTO bears an initial burden of setting forth a
reasonable explanation as to why it believes that the scope of
protection provided by that claim is not adequately enabled by
the description of the invention provided in the [S]pecification
of the application.
In re Wright, 999 F.2d 1557, 1561---62 (Fed. Cir. 1993).
Factors to be considered in determining whether a disclosure
would require undue experimentation ... include ( 1) the
quantity of experimentation necessary, (2) the amount of
direction or guidance presented, (3) the presence or absence of
working examples, ( 4) the nature of the invention, ( 5) the state
of the prior art, ( 6) the relative skill of those in the art, (7) the
4 De Benedittis, EP 0405299 A2, published Jan. 2, 1991.
5 Nicholls, Treatment of postherpetic neuralgia with topical piroxicam gel, 9
New Zealand Med. Journal 233-234 (1993).
8
Appeal2018-008136
Application 14/167,676
predictability or unpredictability of the art, and (8) the breadth
of the claims.
In re Wands, 858 F.2d 731, 737 (Fed. Cir. 1988).
Analysis
The Examiner addresses the Wands factors and provides substantial
evidence of unpredictability and undue experimentation needed to practice
the full scope of the claims. The scope of independent claim 1 encompasses
the treatment of any virus of the family of Herpesviridae, which, as
described by the Specification and the prior art, includes "a great number of
viruses" (FFs 5, 12). The prior art explains that there was no treatment
known to kill herpes viruses (FF 13). Prior art methods for treating acute
herpes neuralgia and post-herpetic neuralagia by topically administering
NSAIDs, including piroxicam, resulted in a reduction of pain and
inflammation (FFs 11, 15-17). In contrast, the scope of independent claim 1
is directed to piroxicam in an amount effective to provide virucidal activity
against any herpes virus. As explained by the Examiner, Appellant's
specification does not distinguish between piroxicam in an amount effective
to treat herpes viruses through virucidal activity, as opposed to the prior art
amounts that mitigate herpes virus symptoms through anti-inflammatory and
analgesic activity (see Ans. 21 ).
Appellant contends "the specification describes topical application of
a gel having an active piroxicam content of 0.5% w/w that is effective for
treatment of herpes viruses, which is all that can be reasonably indicated.
From this description, a skilled person would understand how much
piroxicam to apply" (App. Br. 12). As to virucidal activity Appellant argues
the specification indicates that piroxicam can be effective in
one application (Specification at page 3, lines 12-13 and 22-
9
Appeal2018-008136
Application 14/167,676
(id.).
23) and in less than one day after application to a subject
(Specification at page 3, lines 24--25), which confirms the rapid
virucidal effects described in Test Report 2 (Specification at
page 4, lines 14--19). As such, the specification sufficiently
describes piroxicam's virucidal activity
We do not find Appellant's arguments persuasive. The Specification
does not provide evidence or reasoning that would predictably demonstrate
that the claimed treatment would be expected to treat any herpes virus,
including those without topical manifestations, such as cytomegalovirus and
Epstein-Barr virus (see FFs 12, 13). In view of the broad scope of the
claims, the lack of guidance as to all herpes viruses, and the unpredictability
and lack of known treatments of herpes viruses in the art, we agree with the
Examiner that the Specification does not enable the full scope of claim 1.
Claims 4 and 8 narrow the scope of the virus infection to Herpes
simplex and Herpes labialis, respectively (FFs 2, 3; App. Br. 13). Appellant
states that "Test Reports 1 and 2 deal with herpes simplex viruses" and "Test
Report 1 is particularly relevant for herpes labialis" (App. Br. 13). We
therefore, examine the working examples for particularly enabling the scope
of claims 4 and 8.
Appellant presents Test Report 1 as a working example for topically
administering commercially available piroxicam 0.5% gel to 42 patients (FF
6). The working example noted "signs of amelioration" in at least 38 of 42
patients, with a treatment period ranging from 1 to 10 days (id.). As stated
by the Examiner, amelioration does not necessarily indicate virucidal
activity, as opposed to analgesic or anti-inflammatory activity (see Ans. 20).
The working example does not describe the specific herpes virus that was
treated, e.g., Herpes simplex or Varicella zoster. The working example does
10
Appeal2018-008136
Application 14/167,676
not describe the treatment location, e.g., Herpes labialis or some other
exanthema. The working example does not include the use of a control or
placebo, and it is unclear whether the amelioration is the result of applying
piroxicam, placebo effect, or merely the natural progression of the disease
having a normal duration ofup to 10 days (see FF 11). Because there is no
indication that one skilled in the art would accept without question the
results of Test Report 1 and no evidence has been presented to demonstrate
that Test Report 1 resulted in virucidal activity against herpes virus by
piroxicam, we do not find the first working example to be persuasive
evidence of enablement. See Rasmusson v. SmithKline Beecham Corp., 413
F.3d 1318, 1323 (Fed. Cir. 2005).
Appellant presents Test Report 2 as a working example for the in vitro
virucidal activity of a piroxicam 0.4% gel on cultures infected by Herpes
simplex virus (HSVl) (FF 7). The working example noted a lowering of
virus titer corresponding to a reduction of the virus count by more than
99.99% (id.). As stated by the Examiner, Test Report 2 does not describe
the actual amount of piroxicam applied6 or any in vivo virucidal activity of
piroxicam against HSVl in a patient (Ans. 20). Moreover, in the absence of
a comparative test on a control composition, there is no indication that the
virucidal activity was caused by the active agent as opposed to one of the
components of the gel. As shown in the Feldene® package insert,7
commercially available piroxicam gel contains numerous excipients
including carbopol, propylene glycol, ethyl alcohol, benzyl alcohol, di-
6 Unlike topical administration to a patient, there is no reason why an exact
amount cannot be provided for an in vitro study ( Cf App. Br. 12).
7 Feldene® 0.5% w/w gel (piroxicam), Pfizer Products (2014) (submitted by
Appellant on Oct. 12, 2016).
11
Appeal2018-008136
Application 14/167,676
isopropanolamine, hydroxylethylcellulose, and purified water (Feldene®
package insert 2). Test Report 2 does not describe the contents of the
piroxicam-containing gel, nor the "cultures" used in the "standard testing
methods" (FF 7). Because Test Report 2 does not appear to be a statistically
significant test and does not follow a standard experimental procedure, we
do not accept the results without question. See In re Brana, 51 F.3d 1560,
1567 (Fed. Cir. 1995).
Weighing the evidence of virucidal activity of Test Report 2 against
the high level of unpredictability in treating herpes viruses and the lack of
previous virucidal success, including topical treatment with the same
concentration of piroxicam reported in the prior art, we do not find
Appellant's evidence supporting enablement to be persuasive. Therefore,
we agree with the Examiner that the Specification does not enable claims 4
and 8.
Claim 9 narrows the scope of virus infection to varicella zoster virus
(FF 4, App. Br. 14). Appellant contends "Test Reports 1 and 2 deal with
herpes simplex viruses ... and the related varicella zoster virus is a
particularly susceptible target" (App. Br. 14). The specification describes
"the agent also being effective against herpes zoster VZV" (FF 9). The
working examples do not describe treating varicella zoster virus. Weighing
the Wands factors, including the high level of unpredictability, state of the
art, lack of guidance, and absence of working examples for varicella zoster
virus, we agree with the Examiner that the Specification does not enable
claim 9.
12
Appeal2018-008136
Application 14/167,676
Conclusion of Law
A preponderance of the evidence of record support the Examiner's
conclusion that the Specification does not enable the full scope of claims 1,
4, 8, and 9.
B. 35 U.S. C. § 112, first paragraph, written description
The Examiner determines the claims require "that piroxicam be
incorporated into the recited agent for administration in an amount that is
effective to exhibit virucidal activity against a herpesviridae virus" (Ans. 4).
The Examiner finds that "[t]he originally filed specification and claims,
however, are entirely silent as to the particular amounts of piroxicam that
yield virucidal activity against any ( or all) viruses of the herpesviridae
family" (id.). The Examiner concludes "[a]bsent such description, Appellant
fails to inform the skilled artisan of what amounts of piroxicam actually
satisfy the claimed function. This lack of adequate description demonstrates
that Appellant was not in possession of the full scope of amounts of
piroxicam effective to provide the instantly claimed function" (Ans. 5).
The issue with respect to this rejection is: Does the evidence of record
support the Examiner's conclusion that the Specification fails to provide
descriptive support for the claims?
Principles of Law
"A claim that recites a property that is necessarily inherent in a
formulation that is adequately described is not invalid as lacking written
description merely because the property itself is not explicitly described."
Allergan, Inc. v. Sandoz Inc., 796 F.3d 1293, 1309 (Fed. Cir. 2015).
13
Appeal2018-008136
Application 14/167,676
Analysis
Appellant argues "Piroxicam is a known non-steroidal anti-
inflammatory compound that is used as an analgesic (Specification at page
4, lines 4-7), and gels, creams, [ and] ointments ... containing piroxicam are
known in the art and commercially available" (App. Br. 5). Appellant
argues:
As would be understood by a skilled person, topical application
would entail applying the agent to those areas of a patient
showing disease ... and the amount of gel applied and thus the
amount of piroxicam would vary depending on the size of the
area(s) to be covered
(App. Br. 6).
We are persuaded by Appellant's argument. We find the facts similar
to those considered in Allergan, where the claims recited a formulation in
terms of percent concentration of active agent. See Allergan, 796 F.3d at
1308. Our reviewing court found "the specification[] thus discloses the
claimed formulation as characterized by [ the claimed ingredients], and the
skilled artisan would immediately discern the claimed formulation in [the]
disclosure." Allergan, 796 F.3d at 1308-1309. Here, the Specification
describes a commercially available formulation containing a well-known
active agent in a known concentration. As to the virucidal activity, our
reviewing court in Allergan found "the inherent properties of [the]
formulation ... produce the claimed clinical profile." Allergan, 796 F.3d at
1309. Because the formulation is adequately described even if the property
14
Appeal2018-008136
Application 14/167,676
of the formulation is not, we find that the claims fulfill the written
description requirement. See id. 8
Conclusion of Law
The evidence of record does not support the Examiner's conclusion
that the Specification fails to provide descriptive support for the claims.
SUMMARY
In summary, we affirm the rejection of claims 1, 4, 8, and 9 under 35
U.S.C. § 112, first paragraph, scope of enablement. Claims 2 and 3 fall with
claim 1.
We reverse the rejection of claims 1--4, 8, and 9 under 35 U.S.C.
§ 112, first paragraph, as failing to comply with the written description
requirement.
No time period for taking any subsequent action in connection with
this appeal may be extended under 3 7 C.F .R. § 1.13 6( a).
AFFIRMED
8 We note that it is not inconsistent to affirm the enablement rejection and
reverse the written description rejection because the "written description
requirement [is] separate from an enablement requirement." Ariad Pharm.,
Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) (en bane).
15