Ex Parte Stern et al

Patent Trial and Appeal Board

May 31, 2016

13158672 (P.T.A.B. May. 31, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
13/158,672 06/13/2011
51957 7590 06/02/2016
ALLERGAN, INC.
2525 DUPONT DRIVE, T2-7H
IRVINE, CA 92612-1599
FIRST NAMED INVENTOR
Michael E. Stern
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.
18764(AP) 9925
EXAMINER
JIANG, DONG
ART UNIT PAPER NUMBER
1646
NOTIFICATION DATE DELIVERY MODE
06/02/2016 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 MICHAEL E. STERN and
CHRISTOPHER S. SCHAUMBURG
Appeal2014-006313
Application 13/158,672 1
Technology Center 1600
Before JEFFREY N. FREDMAN, ULRIKE W. JENKS, and
KRISTI L. R. SA WERT Administrative Patent Judges.
SA WERT, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) from the rejection of
claims 1, 2, and 8 of U.S. Patent Application No. 12/158,672 ("the '672
application"). We have jurisdiction under 35 U.S.C. § 6(b). We affirm.
Appellants identify Allergan, Inc. as the real party in interest. Br. 3.
Appeal2014-006313
Application 13/158,672
STATEMENT OF THE CASE
Claims 1, 2, and 8 stand rejected under 35 U.S.C. § 103(a) for
obviousness over De Paiva2 in view of Benson. 3 We choose independent
claim 1 as representative. See 3 7 C.F .R. § 41.3 7 ( c )(1 )(iv). Claim 1
provides:
1. A method for the treatment of an ocular condition
selected from keratoconjunctivitis sicca, diminished corneal
sensitivity, atopic keratoconjunctivitis, vernal
keratoconjunctivitis, ocular cicatricial pemphigoid, or
blepharitis, the method comprising administering to an eye
having the condition a composition comprising an anti-IL-
23p 19 antibody.
Br. 11.
FINDINGS OF FACT
We make the following findings of fact:
1. The claimed invention is directed to a method of treating certain
ocular diseases by administering an antibody that binds to the p 19
subunit of interleukin (IL)-23 (the "anti-IL-23pl9 antibody").
Spec. 2.
2. IL-23 is a cytokine made up of two subunits: p40 and pl9. The p40
subunit is shared with another interleukin, IL-12. Spec. 2.
3. In one embodiment of the claimed invention, the method may be used
2 C.S. De Paiva et al., IL-17 Disrupts Corneal Barrier Following
Desiccating Stress, 2(3) Mucosal Immunol. 243-53 (May 2009).
3 Jacqueline Benson, et al., U.S. Patent No. 7,491,391 B2 (Feb. 17,
2009).
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Application 13/158,672
to treat keratoconjunctivitis sicca, also known as "dry eye" disease.
Patients with dry eye experience chronic dryness of the cornea and
conjunctiva. Spec. 16.
4. De Paiva investigated whether T helper (Th)-17 cell immune response
pathways are involved in human and experimental murine dry eye.
Th-17 represents a subset of T helper cells implicated in immune
defense and autoimmunity. De Paiva 243 (Abstract). De Paiva
describes IL-17 as the "'signature' cytokine of the Th-17 pathway."
Id. 243 (col. 1 ).
5. De Paiva reports that previous studies have shown that differentiation
of Th-17 cells "is driven by IL-6 and transforming growth factor beta
(TGF-B) and requires the lineage-specific transcript factor, retinoid-
related orphan receptor-yt (RORyt)." De Paiva 243 (col. 2, first
paragraph). De Paiva also reports that "IL-23 has been implicated in
the survival and proliferation of Th-17 cells." De Paiva 243 (col. 2).
6. De Paiva tested for the involvement of Th-17 immune response
pathways by measuring the levels of Th-17-associated cytokines in
the conjunctiva of human dry-eye patients. De Paiva found
"[s]ignificantly higher levels ofMMP-9, TNF-a, IL-lB, IL-6, TGF-
B2, IL-23, IL-17, and IFN-y" expression in patients with dry eye than
in normal subjects. De Paiva 244 (col. 1 ). De Paiva also found "a
significant and direct correlation between the levels of expression of
IL-6, IL-23, and TGF-Bl ... with clinical severity" of dry eye.
De Paiva 244 (col. 2).
7. De Paiva also specifically looked for the upregulation of Th-17
inducers on the ocular surface in mice subjected to desiccating stress.
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De Paiva 245 (col. 1-2). De Paiva found that dry eye in mice
"induced a significant increase in IL-6 and IL-23 immunoreactivity in
the cornea and conjunctiva! epithelia," and that "[s]cattered IL-23R-
positive cells were found to infiltrate the conjunctiva! epithelium." Id.
(col. 2). De Paiva concluded that "the ocular surface is a TGF-B, IL-
6, and IL-23-rich environment," and that desiccating stress stimulated
the production of CCL20 and IL-23R, "factors that may facilitate the
influx ofIL-17-producing cells." Id. at 248 (col. 1). De Paiva also
found an increase in the number of IL-17-producing cells in the
cornea and conjunctiva, as well as an increase in IL-1 7 concentration
in tears. Id. (col. 1-2).
8. De Paiva tested the neutralization of IL-17 in vivo in mice by
administering an anti-IL-17 antibody. De Paiva 248 (col. 2).
De Paiva found that antibody neutralization of IL-1 7 ameliorated
corneal epithelial barrier dysfunction in mice with dry eye. Id.; see
also id. (Abstract).
9. De Paiva concluded that "these findings suggest that the ocular
surface environment offers an enabling cytokine milieu for the
differentiation of Th-17 cells in response to desiccating stress."
De Paiva 250 (col. 2). In particular, De Paiva noted that "[ d]ry eye
significantly stimulated the production of IL-23, IL-6, and TGF-B, the
three factors that are important in driving differentiation and survival
of Th-17 cells, in the cornea and conjunctiva." Id. (col. 1 ). De Paiva
also characterized the increased expression ofIL-l 7R and IL-23R in
the conjunctiva and the infiltration of IL-23R+ cells in the
conjunctiva! epithelium as "of particular interest." Id. De Pavia noted
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that "IL-23R is considered as one of the hallmarks of Th-17
differentiation and is not expressed by naive cells." Id.
10. De Paiva does not teach treatment of dry eye with anti-IL-23pl9
antibodies. Ans. 3.
11. Benson discloses a monoclonal anti-IL-23pl9 antibody. Benson
(Abstract).
12. Benson demonstrated that anti-IL-23pl9 antibody inhibits IL-23
receptor binding and neutralizes IL-23 biological function. Benson
(col. 54-55, Examples 2 and 3).
13. Benson teaches that IL-23 consists of two subunits, pl9 and p40, and
that the p40 subunit is shared between IL-23 and IL-12. Benson
(col. 1, 11. 44-46). Benson notes, that even though IL-23 and IL-12
share a structural similarity, the biological functions of IL-23 are
distinct from those of IL-12. Id. (col. 1, 11. 54-57). Specifically, "it is
the IL-23pl9 ligation of the second component of the IL-23 receptor
complex, IL-23R, that confers IL-23 specific intracellular signaling
(e.g., STAT3 phosphorylation) and subsequent IL-17 production by T
cells." Id. (col. 1, 11. 50-53).
14. Benson explains that "there is increasing evidence for the specific role
of IL-23 in immune-mediated disease,' and suggests that
"[ n ]eutralization of IL-23 without inhibition of IL-12 pathways could
then provide effective therapy of immune-mediated disease with
limited impact on important host defense immune mechanism."
"This," Benson suggests, "would represent a significant improvement
over current therapeutic options." Benson (col. 2, 11. 6-12).
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Application 13/158,672
LEGAL STANDARD
A claimed invention is unpatentable if the differences between it and
the prior art are "such that the subject matter as a whole would have been
obvious at the time the invention was made to a person having ordinary skill
in the art." 35 U.S.C. § 103(a) (pre-AIA). To assess whether the subject
matter would have been obvious, the Board follows guidance in Graham v.
John Deere Co., 383 U.S. 1 (1966) andKSRint'l Co. v. Teleflex, Inc., 550
U.S. 398 (2007). "Where a skilled artisan merely pursues 'known options'
from 'a finite number of identified, predictable solutions,' the resulting
invention is obvious under Section 103." In re Cyclobenzaprine
Hydrochloride Extended-Release Capsule Patent Litig., 676 F.3d 1063,
1070 (Fed. Cir. 2012) (quotingKSR, 550U.S. at421).
DISCUSSION
On appeal, the Board "reviews the obviousness rejection for error
based upon the issues identified by appellant, and in light of the arguments
and evidence produced thereon." Ex parte Frye, 94 USPQ2d 1072, 1075-76
(BP AI 2010) (Precedential). Appellants appear to raise two issues on
appeal: ( 1) whether the prior art suggests that dry eye may be treated by
targeting the IL-23 protein, and (2) whether a person of ordinary skill in the
art would have had a reasonable expectation of success in treating an ocular
disease with an anti-IL23pl9 antibody. Br. 8-9.
For the reasons stated below, we agree with the Examiner that,
although the prior art does not explicitly teach the treatment of dry eye or
other ocular diseases with an anti-IL-23pl9 antibody, it would have been
obvious to an ordinarily-skilled artisan based on the combined disclosures of
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Application 13/158,672
De Paiva and Benson to treat dry eye with an anti-IL-23pl9 antibody, as
recited in representative claim 1. Ans. 4-9. We adopt the Examiner's
Answer as our own and address Appellants' arguments as follows.
As to the first issue, Appellants argue that De Paiva "identifies many
inducers of TH-1 7 and other proteins that are elevated in the eyes subject to
desiccating stress, without offering any motivation or suggestion as to why
IL-23pl9 is the specific protein and subunit tied to the disease." Br. 8. But
as the Examiner explained, De Paiva repeatedly suggests a significant
clinical role for IL-23 in the Th-17 immune response pathway involved in
both human and experimental murine dry eye. See Ans. 5-6; see also, e.g.,
FF6 ("a significant and direct correlation between the levels of expression
ofIL-6, IL-23, and TGF-Bl ... with clinical severity" of dry eye); FF7 ("a
significant increase in IL-6 and IL-23 immunoreactivity in the cornea and
conjunctiva! epithelia" of mice with dry eye); FF9 ("[ d]ry eye significantly
stimulated the production ofIL-23, IL-6, and TGF-B, the factors that are
important to in driving differentiation and survival of Th-17 cells, in the
cornea and conjunctiva"). Because De Paiva directly points to a very limited
set of species including IL-23, this is not a situation where a skilled artisan
would have been "required to try all possibilities in a field unreduced by the
prior art." Bayer Schering Pharma AG v. Barr Labs., Inc., 575 F.3d 1341,
1350 (Fed. Cir. 2009).
Moreover, De Paiva provides clear evidence that the Th-17 immune
response pathway plays a role in corneal epithelial barrier disruption in dry
eye, and that antibody neutralization of IL-17-the "signature cytokine of
the Th-17 pathway"-ameliorates corneal epithelial barrier in mice with dry
eye. Ans. 5-6; FF4; FF8. De Paiva also specifically ties IL-23 to the
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"differentiation and survival of Th-17 cells." Ans. 6; FF8-9. Thus, as the
Examiner found and we agree, De Paiva "strongly indicates that targeting
the Th-17 inducers," such as IL-23, "can be used for treating dry eye
disease." Ans. 6.
For these reasons, we reject Appellants' argument that the prior art
discloses so many proteins that the selection of IL-23 would not have been
obvious. Instead, IL-23 represents a "known option[]" from "a finite
number of identified, predictable solutions." KSR, 550 U.S. at 421.
As to the second issue, Appellants argue that De Paiva "provides
insufficient reason for one to conclude, even considering the Benson
reference, that one can treat dry eye disease with a reasonable expectation of
success by inhibiting the pl9 subunit ofIL-23." Br. 9; see also id. (arguing
that De Paiva "does not disclose that dry eye can be treated by targeting the
IL-23 protein, let alone the pl9 subunit of the IL-23 protein"). We agree
with the Examiner that "inhibiting Th-17 response or Th-17 inducers such as
IL-23 for treating [dry eye] would become instantly obvious to a person
having ordinary skill in the art." Ans. 7.
Again, De Paiva teaches the involvement of the IL-17 immune
response pathway in both human and experimental murine dry eye. FF4.
De Paiva also teaches that antibody neutralization of IL-17 ameliorated
corneal epithelial barrier dysfunction in dry eye. Ans. 5-6; FF8. De Paiva
specifically evidences that antibody therapy using an anti-interleukin-17
antibody targeted to this pathway has the capacity to treat dry eye in an
animal model (FF8), a finding that supports the Examiner's finding of a
reasonable expectation of success using an anti-interleukin antibody targeted
to a different pathway component. And De Paiva teaches that IL-23 is one
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Application 13/158,672
of three factors "driving differentiation and survival of Th-17 cells" and that
IL-23 receptor "is considered one of the hallmarks of Th-17 differentiation."
FF9. A skilled artisan looking to treat dry eye would therefore consider
antibody neutralization of other factors involved in the Th-17 immune
response pathway for treating dry eye. Ans. 7. And IL-23 would have been
an obvious target for antibody neutralization based on De Paiva' s repeated
statements about its clinical significance. Id.; see FF6-9. Further, Benson
teaches anti-IL-23 antibodies and specifically shows that anti-IL-23pl9
antibody neutralizes IL-23 biological function. Ans. 7; FFl 1-12. "A
person of ordinary skill has good reason to pursue the known options within
his or her technical grasp." KSR, 550 U.S. at 421. And here, an artisan
seeking to neutralize IL-23 would naturally consider an antibody already
proved to provide that function. Appellants provide no persuasive evidence
that treating dry eye with antibodies directed to IL-23 would have been
outside the ordinarily-skilled artisan's technical abilities.
Moreover, we agree with the Examiner that the ordinarily-skilled
artisan would have targeted the p 19 subunit of IL-23 with a reasonable
expectation of success. Ans. 7. Benson teaches that the p 19 subunit is
specific to IL-23 whereas the only other subunit, p40, is shared with IL-12.
Ans. 7; FF13. And De Paiva shows that IL-12 does not appear to play a role
in the Th-17 immune response pathway because expression ofIL-12 was not
affected by desiccating stress-induced dry eye in mice. Ans. 7; De Paiva
245 (col. 1 ). An artisan seeking to inhibit the biological functions of IL-
23-but not those ofIL-12-would therefore select an anti-IL-23 antibody
specific for the pl9 subunit. Ans. 7; FF14. Additionally, the skilled artisan
would have had a reasonable expectation of success, given that Benson
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demonstrates that an anti-IL-23pl9 antibody neutralizes IL-23 biological
function. Ans. 7; FF 13.
Thus, we agree with the Examiner that, although the prior art does not
explicitly disclose treating an ocular disease with anti-IL-23pl9 antibody,
the prior art adequately suggests that method. Ans. 7; see In re Baird, 16
F.3d 380, 383 (Fed. Cir. 1994) (stating that a "reference must be considered
not only for what it expressly teaches, but also for what it fairly suggests"
(quotation omitted)).
SUMMARY
We affirm the rejection of claims 1, 2, and 8 under 35 U.S.C. § 103(a)
on appeal.
TIME PERIOD FOR RESPONSE
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § l.136(a).
AFFIRMED.
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