Ex Parte Hayardeny

Patent Trial and Appeal Board

Oct 21, 2016

12806275 (P.T.A.B. Oct. 21, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
12/806,275 08/09/2010 Liat Hayardeny
23432 7590 10/21/2016
COOPER & DUNHAM, LLP
30 Rockefeller Plaza
20th Floor
NEW YORK, NY 10112
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.
2609 I
80740-A/JPW/GJG/CS
CONFIRMATION NO.
3699
EXAMINER
N ANOV A, SVETLANA M
ART UNIT PAPER NUMBER
1627
MAILDATE DELIVERY MODE
10/21/2016 PAPER
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.
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte LIAT HAY ARDENY1
Appeal2015-004928
Application 12/806,275
Technology Center 1600
Before ERIC B. GRIMES, JOHN G. NEW, and
RACHEL H. TOWNSEND, Administrative Patent Judges.
TOWNSEND, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a method
for treating Huntington's disease, which have been rejected as obvious. We
have jurisdiction under 35 U.S.C. § 6(b).
We reverse.
STATEMENT OF THE CASE
"Huntington's disease (HD) is a neurodegenerative disorder
characterized by motor, cognitive, and psychiatric symptoms and by a
progressive degeneration of neurons in basal ganglia in brain cortex." (Spec.
2.) "Patients suffering from HD have significantly lower BDNF[, i.e.,
1 Appellant identifies the Real Party in Interest as Teva Pharmaceutical
Industries, Ltd. (Appeal Br. 5.)
Appeal2015-004928
Application 12/806,275
brain-derived neurotrophic factor,] levels in serum compared to healthy
controls." (Id.) "Several agents have been identified to increase BDNF
levels including riluzole and antidepressants such as fluoxetine." (Spec. 4.)
Appellants' invention is directed at the use of "[l]aquinimod, which has been
shown to increase BDNF in humans" to treat HD. (Spec. 5.)
Claims 36--45 are on appeal. Claim 36 is representative and reads as
follows:
36. A method for treating a human subject suffering from
Huntington's disease, consisting essentially of periodically
administering an amount of laquinimod or a pharmaceutically
acceptable salt thereof effective to treat the human subject.
(Appeal Br. Ex. Al.)
The following ground of rejection by the Examiner is before us on
review:
Claims 36--45 under 35 U.S.C. § 103(a) as unpatentable over Chen,2
Polman,3 Sandberg-Wollhelm,4 Chen 2,5 and Bjork. 6
2 Chen et al., Kynurenine pathway metabolites in humans: disease and
healthy states, 2 Int. J. Tryptophan Res., 1-19 (2009).
3 Polman et al., Treatment with laquinimod reduces development of active
MRI lesions in relapsing MS, 64 Neurology, 987-91 (2005).
4 Sandberg-Wollhelm et al., 48-week open safety study with a high-dose oral
laquinimod in MS patients, Abstractverwaltung AKM AG, (2005).
5 Chen et al., Recent advances in the treatment of amyotrophic lateral
sclerosis. Emphasis on kynurenine pathway inhibitors, 9(1) Central Nervous
Sys. Agents in Med. Chem. 32-9 (2009) ("Chen 2" or "Chen2").
6 Bjork et al., US 6,077,851, issued June 20, 2000.
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Application 12/806,275
DISCUSSION
The Examiner finds that both Chen articles disclose that imbalances in
the kynurenine pathway ("KP") have been demonstrated to be involved in
Huntington's disease ("HD"), Alzheimer's disease ("AD"), amyotrophic
lateral sclerosis ("ALS") and multiple sclerosis (MS"). (Final Action 13, 15;
Ans. 5-7, 13-14.) The Examiner further finds that both Chen articles
indicate that studies suggest quinolinic acid plays a significant pathological
role in the development of neurodegenerative disorders, such as HD. (Id.)
The Examiner finds that Chen2 indicates that injection of quinolinic acid
(also called QUIN in Chen2) has been shown in in vivo testing to result in
development of lesions characteristic of HD. (Final Action 15; Ans. 7, 14.)
The Examiner further finds that Chen teaches there are "several
therapeutic agents either on the market or undergoing clinical trials, which
are either analogues of neuroprotective kynurenine or act to inhibit the
production of quinolinic acid," including laquinimod. (Final Action 13,
Ans. 5.) The Examiner finds that Chen Figure 2 discloses at what point in
the KP laquinimod acts. (Ans. 14.) The Examiner further finds that Chen
teaches "laquinimod has shown delaying of disease progression in
experimental autoimmune encephalitis (EAE) (as MS animal model), as well
as successfully reduced the development of active lesions in patients with
relapsing MS." (Final Action 13-14; Ans. 5.) According to the Examiner,
though, Chen is not "limited to [teaching] the treatment of MS" with
laquinimod, because "it discloses a role for laquinimod in overall
modification of the kynurenine pathway, not limited to MS." (Ans. 12-13.)
The Examiner finds that Chen2 also refers to the laquinimod studies in MS,
and adds that "in the treatment of ALS, there has also been an emphasis on
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Application 12/806,275
kynurenine pathway inhibitors, such as laquinimod." (Final Action 15; Ans.
14.)
The Examiner relies on Polman and Sandberg-Wollman for teaching
studies that indicate the safety, tolerability and efficacy in MS patients of
laquinimod from 0.3 mg/day up to 0.9 mg/day, and that 2.4 mg/day has been
used, but with some side effects. (Final Action 14; Ans. 6-7.)
According to the Examiner, one of ordinary skill in the art would have
found it obvious to try using laquinimod in treating HD with "a reasonable
chance" or "expectation of success" based on the foregoing. (Final Action
15-16; Ans. 6-8, 14-15, 23.) The Examiner contends one of ordinary skill
in the art would have been motivated to try laquinimod because "Chen and
Chen 2 ... disclose that studies have provided strong evidence suggesting
that quinolinic role [sic, acid] plays a pathological role in the development of
a number of neurodegenerative disorders, such as HD, MS, ALS and AD"
and because "Chen, Polman and Sandberg-Wollman show[] that laquinimod
has shown good safety and efficacy in patients with MS" and because "Chen
2, clearly contemplates laquinimod as an experimental therapeutic for other
neurodegenerative diseases beyond MS, namely ALS, and suggests a further
link between HD and these diseases." (Final Action 15-16; Ans. 6-8, 23.)
We disagree with the Examiner's factual findings regarding the
teaching of Chen2, as well as the Examiner's conclusion of obviousness.
We agree with Appellant that the references do not provide a reasonable
expectation of success of using laquinimod in HD.
The essence of the rejection is based on an improper obvious to try
argument since there is no evidence of what the mechanism of action of
laquinimod in treating MS is, much less that HD involves a similar
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mechanism of action such that laquinimod would be expected to be effective
in treating HD. Indeed, as Appellant indicates, Chen2 reports that "the
mechanism of action of laquinimod was unknown (page 34, right column)."
(Appeal Br. 16.) Furthermore, while Chen2 describes effects of the
treatment with laquinimod on MS, i.e., "inhibit[ing] disease progression and
infiltration of CD4+ T-cells and macrophages into the central nervous
system (CNS) ... shift[ing] the cytokine profile towards T helper (Th)
2/Th3 cytokines, interleukin (IL )-4, IL-10 and transforming growth factor
(TGF)-B ... [and] act[ing] synergistically with IFN-B," (Chen2 34,) there is
no indication that any one of these effects or their combination would result
in treatment of HD.
The fact that both diseases involve the kynurenine pathway (KP) and
result in the production of lesions is not sufficient. As Appellant notes,
"[t]here is no disclosure whether KP imbalance is the root cause or
consequence of HD; and, therefore, no disclosure from which a person
having ordinary skill in the art could have determined whether addressing
the KP imbalance would be helpful in treating HD." (Appeal Br. 15-16.)
That Chen2 confirms QUIN is involved in creating "lesions characteristic of
Huntington's disease" (Chen2 33), does not establish that KP imbalance is
the root cause or consequence of HD. Moreover, that Chen in Figure 2
discloses at what point in the KP laquinimod takes part, does not establish its
mechanism of action in any particular disease. Thus, we also disagree with
the Examiner (Ans. 12-13) that Chen more broadly teaches the use of
laquinimod to treat patients with diseases other than relapsing MS. (Chen
14.)
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We also disagree with the Examiner that Chen2 teaches "an emphasis
on kynurenine pathway inhibitors, such as laquinimod" in the "treatment of
ALS" (Final Action 15; Ans. 6). Chen 2, like Chen, notes the studies of
laquinimod in MS but does not go so far as to say laquinimod would be
expected to treat ALS in light of the foregoing. (Chen2 34.) Chen2
describes several drugs undergoing phase III trials for ALS and notes that
they are not directed at the kynurenine pathway.
Chen2 discloses that the KP has been recently associated with ALS
and separately identifies a list of a number of drugs known or being studied
with regard to their modulation of the KP either by ( 1) being an
"analogue[]of the neuroprotective kynurenines; [or] (2) [] inhibit[ing] the
synthesis of the neurotoxic QUIN". (Chen2 34.) Laquinimod is but one
compound in this list. (Id.)
Chen2 hypothesizes that because "compounds that regulate or inhibit
the KP have demonstrated very promising results in both preclinical and
clinical trials of neurological diseases [such as clioquinol and PBT2 in AD,
Transilast in EAE, Leflunomide in autoimmue neuritis and EAE, and
laquinimod in EAE and MS] ... there is strong evidence supporting the
possible positive outcome of testing these drugs in ALS and also in
developing therapeutic interventions aimed at targeting the KP." (Chen2
34-3 5 (emphasis added).) That there is strong evidence supporting the
possible positive outcome of testing these drugs is not the same as strong
evidence supporting a positive outcome in treating patients with ALS.
While the latter could likely support a reasonable expectation of success, the
former possibility does not. In short, at best, Chen2 indicates one has a
reason to test laquinimod in an ALS model, but it does not provide a
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reasonable expectation of success of treating ALS simply because
laquinimod modulates the KP and has been shown to provide positive results
in MS.
Thus, we disagree with the Examiner that Chen2 "clearly
contemplates laquinimod as an experimental therapeutic for other
neurodegenerative diseases beyond MS, namely ALS." (Ans. 7-8.)
Because Chen2 cannot be said to provide a reasonable expectation of
success for treating ALS with laquinimod, the mere fact that Chen2
discloses that QUIN, a neurotoxin of the KP pathway which is thought to be
involved in ALS, "results in the development of axon-sparing lesions,
characteristic of Huntington's disease" (Chen2 33) is not indicative of a
reasonable expectation of success for treating HD with laquinimod.
For the foregoing reasons, the decision of the Examiner rejecting
claims 36--45 under 35 U.S.C. § 103(a) as unpatentable over Chen, Polman,
Sandberg-Wollhelm, Chen 2, and Bjork is reversed.
SUMMARY
We reverse the rejection of claims 36--45 under 35 U.S.C. § 103(a) as
unpatentable over Chen, Polman, Sandberg-Wollhelm, Chen 2, and Bjork.
REVERSED
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