Ex Parte Jiang et al

Patent Trial and Appeal Board

May 15, 2018

14035622 (P.T.A.B. May. 15, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
14/035,622 09/24/2013
51957 7590 05/17/2018
ALLERGAN, INC.
2525 DUPONT DRIVE, T2-7H
IRVINE, CA 92612-1599
FIRST NAMED INVENTOR
Guang-Liang Jiang
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.
19230US (BOT) 1626
EXAMINER
FAN,LYNNY
ART UNIT PAPER NUMBER
1651
NOTIFICATION DATE DELIVERY MODE
05/17/2018 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):
patents_ip@allergan.com
pair_allergan@firsttofile.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte GUANG-LIANG JIANG and CATHERINE TURKEL
Appeal2017-005290
Application 14/035,622
Technology Center 1600
Before ERIC B. GRIMES, JEFFREY N. FREDMAN, and RYAN H. FLAX,
Administrative Patent Judges.
FREDMAN, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal 1 under 35 U.S.C. § 134 involving claims to a method
of treating osteoarthritis-mediated cartilage degradation by intra-articular
injection of a botulinum toxin type A. The Examiner rejected the claims as
obvious. We have jurisdiction under 35 U.S.C. § 6(b). We reverse.
Statement of the Case
Background
"Arthritis is one of the most prevalent chronic health problems and
one of the most common causes of disability in America. . . . The goals of
current therapies for arthritis, including osteoarthritis, are to alleviate pain
1 Appellants identify the real party in interest as the Allergan, Inc. (see App.
Br. 3).
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Application 14/035,622
and other related arthritis associated symptoms" (Spec. ,r,r 2-3). "While the
current therapies may provide short term relief for pain and other
osteoarthritis associated symptoms, they do not address the underlying
structural problem .... Thus, there is a need for treatment methods that
modify progression of arthritis, such as osteoarthritis" (Spec. ,r 4).
The Claims
Claims 19-23, 26-29, and 31 are on appeal. Independent claim 26 is
representative and reads as follows:
26. A method for modifying the levels and/or activities of at
least one agent associated with osteoarthritis-mediated cartilage
degradation in a patient in need thereof, the method comprising
locally administering a therapeutically effective amount of a
botulinum toxin type A to an osteoarthritis-affected site of the
patient, thereby mitigating the osteoarthritis-mediated cartilage
degradation; wherein the administering is by intra-articular
injection; wherein the therapeutically effective amount is
greater than 300 units; and wherein the botulinum toxin type A
is onabotulinumtoxinA.
The Issue
The Examiner rejected claims 19-23, 26-29, and 31 under 35 U.S.C.
§ 103(a) as obvious over Boon2 (Final Act. 3--4).
The Examiner finds Boon teaches
a method for evaluating the efficacy of an intra-articular
injection ofBoNT-A in patients for osteoarthritis of the knee
(p.269 col right - para 1 ), comprising intraarticularly injecting
200 units of Botox ( onabotulinumtoxinA, a botulinum toxin
type A) into the knee joint of patients (p.270 col left - para 1,3),
2 Boon et al., Efficacy of Intra-Articular Botulinum Toxin Type A in
Painful Knee Osteoarthritis: A Pilot Study, 2 PM&R 268-76 (2010).
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wherein intra-articular injection of 200 units of Botox
( onabotulinmntoxinA) results in decreases in pain (p.272 col
left- para 2).
(Final Act. 3). The Examiner acknowledges that Boon "does not specifically
identify modifying the levels and/or activities of at least one agent associated
with osteoarthritis-mediated cartilage degradation" and "does not teach the
claimed amount of Botox" (id. at 4).
The Examiner finds Boon, by "administering the same active agent to
the same treating population in the same form of administration" inherently
"must also modify the levels and/or activities of at least one agent associated
with osteoarthritis-mediated cartilage degradation." (Final Act. 4). The
Examiner also finds the ordinary artisan would have found it obvious "to
optimize the amount of Botox ( onabotulinumtoxinA) as a matter of routine
experimentation, since the appropriate dosage is generally determined on a
case by case basis by the attending physician based on the age, weight, size,
and medical condition of the patient" (id.).
The issue with respect to this rejection is: Does the evidence of
record support the Examiner's conclusion that the ordinary artisan would
have found it obvious to optimize the therapeutic dosages of
onabotulinumtoxin A to greater than 300 units as required by claims 26 and
31?
Findings of Fact
1. Boon teaches the "specific aim of the current study was to
evaluate the short-term efficacy of a single intra-articular injection of BoNT-
A in patients with chronic, symptomatic knee OA" (Boon 269, col. 2).
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2. Boon teaches
Eligible patients had to be at least 40 years of age with a
primary diagnosis of unilateral, symptomatic, mild-to-moderate
knee OA on the basis of both clinical and radiographic findings.
. . . Patients had to have knee pain 6/10 or greater on the visual
analog scale (VAS) that interfered with function most days of
the week
(Boon 269, col. 2, citation omitted).
3. Boon teaches patients were assigned "to 1 of 3 treatment
groups: intra-articular corticosteroid ( 40 mg of methylprednisolone acetate
injectable suspension), low-dose BoNT-A (100 units), or high-dose BoNT-A
(200 units)" (Boon 27 0, col. 1 ).
4. Boon teaches: "Both pain VAS and WOMAC pain scores
decreased within each treatment group; however, changes in pain VAS were
only statistically significant for the low-dose BoNT-A group" (Boon 271,
col. 2).
5. Boon teaches:
We compared a novel use of a well-known drug (BoNT-
A) to a treatment that is the current standard of care (intra-
articular corticosteroid) and demonstrated significant
improvement in WOMAC pain scores in all 3 groups. Pain
VAS scores also improved in all groups at 8 weeks but only
reached statistical significance in the low-dose BoNT-A group
(with improvement maintained up to 6 months). However, no
significant between group differences were noted, suggesting a
lack of power as the result of small sample size, a small effect
size for BoNT-A, and/or improvement noted (and expected) in
the intra-articular corticosteroid group. The authors did note
significant improvements in secondary outcomes of function in
all 3 treatment groups. The improvements in WOMAC
physical function and stiffness were similar across groups.
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Improvements in 40 meter walk time were noted in all groups
but only reached statistically significant levels in the low-dose
BoNT-A and corticosteroid groups.
(Boon 275, col. 1).
6. Boon teaches "the current study does not support the use of 200
units ofBoNT-A for intra-articular injection. Nonetheless, it was reassuring
that the high-dose BoNT-A group did not show any increase in adverse
effects in comparison with more standard-dose BoNT-A or to intra-articular
corticosteroids" (Boon 275, col. 1 ).
7. The Specification teaches the "quantity of toxin administered
and the frequency of its administration will be at the discretion of the
physician responsible for the treatment and will be commensurate with
questions of safety and the effects produced by a particular toxin
formulation" (Spec. ,r 67).
8. The Specification teaches: "The therapeutically effective
amount of the clostiridial [sic] derivative ... can vary according to the
potency of the toxin and particular characteristics of the condition being
treated, including its severity and other various patient variables including
size, weight, age, and responsiveness to therapy" (Spec. ,r 66).
9. The Specification teaches studies where a "single 200 U (2 mL)
dose of a botulinum toxin Type A (BOTOX®) was injected into the intra-
articular space of the study knee" (Spec. ,r 85, Example 1; cf Spec. ,r,r 105,
109, 113, 117, 120, Examples 7, 8, 9, 10, 11). The Specification provides
prophetic examples of treatment with 100 U injected BOTOX® (Spec.
,r 125, Example 13) and about 300 U injected BOTOX® (Spec. ,r 128,
Example 14).
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Principles of Law
"The normal desire of artisans to improve upon what is already
generally known can provide the motivation to optimize variables." In re
Ethicon, Inc., 844 F.3d 1344, 1351 (Fed. Cir. 2017). However, where "the
only evidence of motivation in the present record is that of researchers to
make smaller [compounds] ... [t]hat motivation would not have supplied
researchers with a reason to make [compounds] ... encompassing larger
[compounds]." Genetics Inst., LLC v. Novartis Vaccines & Diagnostics,
Inc., 655 F.3d 1291, 1306 (Fed. Cir. 2011).
Analysis
Appellants contend
as Boon explicitly teaches that the low-dose BoNT-A (100
units) is much more effective than the high dose BoNT-A (200
units) in reducing pain, stiffness and function and has a longer
therapeutic duration (26 weeks), a skilled artisan would not
have been motivated to use the high dose of 200units ... let
alone arbitrarily increase the dose to produce the claimed
therapeutically effective amount of greater than 300 units.
(App. Br. 13). Appellants contend "the Office has failed to provide a
rational underpinning as to why a skilled artisan would have ignored Boon's
teachings of a more effective and safer low dose BoNT-A and instead would
have randomly performed routine experimentation and increased the dose to
produce the claimed methods" (Id.).
The Examiner responds:
The teaching (of Boon) of low-dose BoNT-A (100 units)
statistically significantly decreases pain VAS, stiffness and
function and has a longer therapeutic duration compared to
high-dose BoNT-A (200 units) does not teach away from using
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greater than 300 units as recited in claim 31 (argued by the
appellant), since ... Boon does not "criticize, discredit or
otherwise discourage" administering greater than 300 units of
BoNT-A to an osteoarthritis-affected site of a patient.
(Ans. 7).
We find that Appellants have the better position. While we agree with
the Examiner that the therapeutic concentration of botulinum toxin type A is
an optimizable variable, Boon undercuts the optimization rationale by
teaching "the current study does not support the use of 200 units ofBoNT-A
for intra-articular injection" (FF 6). That is, to the extent that Boon provides
reason to optimize the amounts of botulin um toxin type A for this treatment,
Boon suggests reducing the levels below 200 units to avoid adverse effects
(FF 6) rather than increasing the levels above 200 units to the "greater than
300 units" required by independent claims 26 and 31.
While Boon's statement may not represent a teaching away, because
Boon does not directly criticize the use of higher amounts, we agree with
Appellants that the ordinary artisan would not have had reason to optimize
to higher amounts in view of the absence of evidence of improved efficacy
by a 200 unit formulation relative to a 100 unit formulation along with the
concern of increased risk of adverse effects.
Conclusion of Law
The evidence of record does not support the Examiner's conclusion
that the ordinary artisan would have found it obvious to optimize the
therapeutic dosages of onabotulinumtoxin A to greater than 300 units as
required by claims 26 and 31.
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SUMMARY
In summary, we reverse the rejection of claims 19--23, 26-29, and 31
under 35 U.S.C. § 103(a) as obvious over Boon.
REVERSED
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