Ex Parte Annat et al

Patent Trial and Appeal Board

Aug 22, 2018

13813006 (P.T.A.B. Aug. 22, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
13/813,006 04/08/2013
23911 7590 08/30/2018
CROWELL & MORING LLP
INTELLECTUAL PROPERTY GROUP
P.O. BOX 14300
WASHINGTON, DC 20044-4300
FIRST NAMED INVENTOR
Jocelyne Annat
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.
102846.65274US 5872
EXAMINER
FAY,ZOHREHA
ART UNIT PAPER NUMBER
1617
NOTIFICATION DATE DELIVERY MODE
08/30/2018 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):
edocket@crowell.com
tche@crowell.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte JOCELYNE ANNAT, HELENE-CELINE HUGUET,
OLIVIER LACOMBE, and LUC LEBRETON
Appeal 2017-007961 1
Application 13/813,006
Technology Center 1600
Before FRANCISCO C. PRATS, ULRIKE W. JENKS, and
TIMOTHY G. MAJORS, Administrative Patent Judges.
PRATS, Administrative Patent Judge.
DECISION ON APPEAL
This appeal under 35 U.S.C. § 134(a) involves claims to methods of
treating non-infectious uveitis. The Examiner rejected the claims for
obviousness.
We have jurisdiction under 35 U.S.C. § 6(b)(l).
We affirm.
STATEMENT OF THE CASE
The sole rejection before us for review is the Examiner's rejection of
claims 26-30 and 34--37 under 35 U.S.C. § 103(a) as being unpatentable
1 Appellants identify Laboratoires Fournier SA as the real party in interest.
Br. 1.
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over Nishi2 and Renaut. 3 Final Act. 3---6; Ans. 2--4.
Claim 26, the only independent claim on appeal, is representative and
reads as follows:
26. A method of treating non-infectious uveitis, severe
conjunctivitis, dry eye syndrome or diabetic retinopathy, which
comprises administering to the eye of a subject in need thereof
a pharmaceutical composition comprising a therapeutically
effective amount of a compound of formula (I) or of a
pharmaceutically acceptable salt thereof as sole active
ingredient of said composition, together with excipients suitable
for ocular administration:
(l)
in which:
- n is equal to 6 or 8,
- A is a bond, a group CH2, a group CH(OH), a group CHF, a
group CH(OCH3), a group CH2NH or a group CH20,
- R is H or CH3.
Br. A-1 (Claims App.).
DISCUSSION
The Examiner's Prima Facie Case
In rejecting claims 26-30 and 34--37 for obviousness, the Examiner
cited Nishi as disclosing the "use of a group of compounds in a
pharmaceutical formulation as immunosuppressant, which can be in
2 EP 1 471 054 Al (published Oct. 27, 2004).
3 EP O 600 762 Bl (published Jul. 10, 1996). In citing to Renaut, we cite to
US 5,476,870 (issued Dec. 19, 1995) as the English language equivalent, as
do Appellants. See Br. 2; see also Ans. 3 (citing US 5,476,870 when citing
to Renaut).
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combination with other immunosuppressive agents, such as [Appellants']
claimed compounds for the treatment of conditions, such as, uveitis and
diabetic retinopathy." Ans. 3 ( citing Nishi ,r 17 and pp. 30, 31 ).
The Examiner found that Nishi differs from the rejected claims "in the
use of the composition in the form of an eye drop or by an injectable or
implantable system." Id.
As evidence that the claimed methods would nonetheless have been
obvious to an ordinary artisan, the Examiner cited Renaut as "teach[ing] the
use of [Appellants'] claimed compounds in a pharmaceutical formulation as
immunosuppressant" and found that Renaut taught "ocular and topical
administration" of those compounds. Id.
Based on the references' combined teachings, the Examiner reasoned
that an ordinary artisan would have considered it obvious "to use the
claimed compounds topically for the treatment of uveitis and diabetic
retinopathy, motivated by the teachings of [Renaut ], which teaches the
ophthalmic and ocular administration of the claimed compounds as old and
well known." Id. at 3--4.
In particular, the Examiner reasoned, the references' combined
teachings "make clear that the claimed compounds have immunosuppressive
activity and have been used in combination with other immunosuppressive
agents for the treatment of uveitis. The secondary reference [Renaut] makes
clear that the ophthalmic use of the claimed compounds is considered to be
old and well known." Id. at 4.
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Analysis
As stated inJn re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992):
[T]he examiner bears the initial burden ... of presenting a
prima facie case of unpatentability ....
After evidence or argument is submitted by the applicant in
response, patentability is determined on the totality of the
record, by a preponderance of evidence with due consideration
to persuasiveness of argument.
In the present appeal, although we find that the Examiner's
interpretation of claim 26, as encompassing active ingredients in addition to
the compound of formula (I), is not consistent with the express language in
the claim, we find that the preponderance of the evidence nonetheless
supports the Examiner's conclusion of obviousness as to claim 26.
Specifically, claim 26 recites a method of treating non-infectious
uveitis, severe conjunctivitis, dry eye syndrome, or diabetic retinopathy. Br.
A-1 (Claims App.). Claim 26 recites "administering to the eye of a subject
in need thereof a pharmaceutical composition comprising a therapeutically
effective amount of a compound of formula (I) or of a pharmaceutically
acceptable salt thereof as sole active ingredient of said composition." Id.
( emphasis added).
Because claim 26 expressly states that the compound of formula (I) or
its salt is the sole active ingredient in the administered composition, the
Examiner does not persuade us (see Ans. 4), that claim 26 permits active
ingredients other than the compound of formula (I) or its salt in the
compound administered according to claim 26.
We acknowledge, as the Examiner contends (see id.), that Appellants'
dependent claim 36 recites administering another active agent (see Br. A-2-
A-3). However, the second active ingredient is recited as being in "a second
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pharmaceutical composition" that is administered separately from the
composition administered according to claim 26. See id. Accordingly, the
Examiner does not persuade us that the composition recited in claim 36
compels interpreting claim 26 as permitting active ingredients other than the
compound of formula (I) or its salt in the administered compound.
Turning to the cited prior art, as the Examiner found, and Appellants
do not dispute, Renaut teaches that compounds encompassed by claim 26 's
formula (I) "have a greater activity in the field of immunosuppression than
the known products of the prior art." Renaut 1 :47--49; see also id. at 2:22-
23 ( disclosing the use of its compounds in "a drug intended for use in
therapeutics to combat immune disorders").
As the Examiner found, Renaut discloses that its compounds may be
administered in a variety of ways, including "orally, by injection, especially
intramuscular or intra venous injection, topically, especially in the form of a
cream for local application or eye drops, transdermally, by suppository or by
inhalation." Id. at 24:2-5.
Given these teachings, we discern no error in the Examiner's finding
(see Ans. 5), that Renaut suggests administering its compounds, which are
undisputedly encompassed by formula (I) in Appellants' claim 26, as the
sole active agent in an immune-suppressing composition in the form of eye
drops. We acknowledge, as Appellants contend (Br. 7), that Renaut does not
disclose administering its compounds to the eye for the treatment of uveitis,
severe conjunctivitis, dry eye syndrome, or diabetic retinopathy, as claim 26
reqmres.
Nishi, however, discloses that uveitis and diabetic retinopathy are
disorders that are treatable using immune-suppressing agents, as the
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Examiner found. See Nishi ,r 17 ( disclosing its inventive "new compounds
having excellent immunosuppressive activity" as being "useful as preventive
or therapeutic agents for autoimmune diseases or other immunology-related
diseases such as ... uveitis ... and diabetic retinopathy").
Nishi, moreover, discloses that the compounds of its invention may be
combined with other "'[i]mmunosuppressants"' including "tresperimus" and
"anisperimus" (id. ,r 82), both of which are described in Appellants'
Specification as being preferred compounds encompassed by claim 26 's
formula (I). See Spec. 4: 1-3.
Thus, on the current record, the cited references establish that uveitis
and diabetic retinopathy were among disorders suitable for treatment with
immunosuppressant compositions that include tresperimus and anisperimus
(Nishi), and also establish that those compounds were useful by themselves
in immunosuppressant compositions formulated as eye drops (Renaut).
Given those teachings, Appellants do not persuade us that an ordinary
artisan lacked an adequate reason for, or lacked a reasonable expectation of
success in, using Renaut's eye drops for treating uveitis and/or diabetic
retinopathy.
Given the discussed teachings in Nishi and Renaut, moreover,
Appellants do not persuade us (see Br. 10) that an ordinary artisan would
have arrived at the method recited in claim 26 only through improper
hindsight. As to Appellants' contentions that the teachings in the cited
references are not enabling (id. at 7-8), our reviewing court has advised that
"[u]nder § 103, ... a reference need not be enabled; it qualifies as a prior art,
regardless, for whatever is disclosed therein." Amgen, Inc. v. Hoechst
Marion Roussel, Inc., 314 F.3d 1313, 1357 (Fed. Cir. 2003) (remanding case
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to district court to reconsider obviousness without reference to whether prior
art patent at issue was enabled).
That Nishi included uveitis and diabetic retinopathy in a list of about
100 other disorders treatable with immunosuppressants, and that Nishi did
not include examples relating to uveitis and diabetic retinopathy (see Br. 5-
7), do not persuade us that Nishi would have failed to suggest using known
immunosuppressants, such as tresperimus and anisperimus, to treat uveitis
and/or diabetic retinopathy. See Merck & Co. v. Biocraft Labs., Inc., 874
F.2d 804, 807 (Fed. Cir. 1989) (species claim held obvious where it recited
one of 1200 possible combination embodiments disclosed by reference and
where reference suggested no preference for claimed embodiment); see also
In re Mills, 470 F.2d 649, 651 (CCPA 1972) ("All the disclosures in a
reference must be evaluated, including nonpreferred embodiments, and a
reference is not limited to the disclosure of specific working examples."
( Citations omitted)).
We acknowledge, as Appellants contend (Br. 5), that Nishi discloses
using tresperimus and anisperimus as immunosuppressants in combination
with the other compounds described in Nishi, rather than as a sole active
ingredient as required by Appellants' claim 26. As noted above, however,
Nishi discloses that tresperimus and anisperimus were known
immunosuppressant compounds. See Nishi ,r,r 82, 83. Accordingly, despite
Nishi' s preference for combining those compounds with other
immunosuppressant compounds, Appellants do not persuade us that an
ordinary artisan lacked adequate reason for, or a reasonable expectation of
success in, using one of those compounds as the sole active ingredient when
treating uveitis and/or diabetic retinopathy, particularly given Renaut's
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disclosure of formulating eye drops containing those compounds as the sole
active ingredient. See Renaut 24:4.
We acknowledge, but are not persuaded by, Appellants' assertions
that "prior to Appellant's specification, it was believed by the skilled artisan
that various immunosuppressants, including compounds of formula (I)
would likely trigger an overactive immune response in patients, causing
undesired side effects" and that, "[i]n light of the highly immunosuppressive
properties of tresperimus and anisperimus, a skilled artisan would have
expected tresperimus or anisperimus to provoke a systemic immune
response upon administration." Br. 9. Appellants cite to no specific
evidence supporting these assertions. It is well settled that unsupported
attorney argument is entitled to little probative weight in relation to the
question of obviousness. See In re Geisler, 116 F.3d 1465, 1471 (Fed. Cir.
1997). Accordingly, on the present record, we do not find these assertions
persuasive as to what an ordinary artisan would have expected based on the
teachings in Renaut and Nishi.
that
Br. 9.
We acknowledge, but are not persuaded by Appellants' contention
as reflected by the Thompson Pharma ® database reports, noted
in the Reply to Office Action dated April 23, 2015, although
both tresperimus and anisperimus were developed in the late
1990's as potential immunosuppressant drugs for use in
autoimmune disease or organ transplant rejection, the
development of both drugs was halted in 2003.
MPEP § 1205.02 explains (emphasis added):
It is essential that the Board be provided with a brief fully
stating the position of the appellant with respect to each ground
of rejection presented for review in the appeal so that no search
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of the Record is required in order to determine that position.
Thus, the brief should not incorporate or reference previous
responses.
In addition to improperly referencing a previous response, Appellants
fail to identify any specific teaching in the cited report that explains with
particularity why development of tresperimus and anisperimus was
discontinued, such that the alleged discontinuation of the compounds'
development in drug formulations might be indicative of, or linked to, the
compounds' use as immunosuppressants in treating uveitis or diabetic
retinopathy.
We acknowledge also Appellants' contention that, even if a skilled
artisan were motivated to formulate tresperimus or anisperimus for ocular
administration, the artisan would not have expected those compounds to
reach "the posterior chamber of the eye where such compounds may display
activity against ocular inflammatory disease without triggering an immune
response that would militate against use of such drugs. This is because the
posterior chamber of the eye is filled with aqueous humor." Br. 10 ( citing
Spec. at Fig. 5).
Appellants, however, do not explain specifically, or identify
persuasive supporting evidence explaining, how or why the presence of the
aqueous humor, or the uveitis data in Appellants' Figure 5, demonstrate that
a skilled artisan lacked a reasonable expectation of success in administering
a composition containing only tresperimus or anisperimus to the eye for
treating uveitis or diabetic retinopathy.
In sum, for the reasons discussed, Appellants do not persuade us that
the prior art evidence of obviousness advanced by the Examiner fails to
suggest the process recited in Appellants' claim 26.
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Turning to the objective evidence of nonobviousness, Appellants cite
to the following passages from the Specification as evidence that the process
recited in claim 26 produces unexpected results:
The present invention is based on unexpected results
demonstrating that the compounds of formula (I) (hereafter
referred to as "compounds of the invention") and their
pharmaceutically acceptable salts are able, when administered
locally, to improve clinical signs in uveitis models, and
especially protect the blood ocular barrier and the ocular tissues
of the anterior and posterior chamber without modification of
the systemic immune response. The compounds of the
invention are likewise useful for the treatment of severe
conjunctivitis, dry eye syndrom[ e] and diabetic retinopathy.
Spec. 3 :2-9.
[I]njection of tresperimus in the posterior pole of the eye, in the
posterior zone of the ciliary body, enabled its diffusion in the
anterior and posterior segments of the eye as shown by its
efficacy on the anterior and posterior ocular inflammation in
EAU [Experimental Auto-Immune Uveoretinis in rat].
Moreover, low levels ( < 90ng/mL) of tresperimus were found
in the plasma without any effect on the immune system
response. In fact, the effect of tresperimus was limited to the
eye, which confirms that no effective diffusion took place in the
general circulation.
We have shown that three intravitreal injections of tresperimus
after immunization with S-Ag [purified retinal autoantigen]
during the afferent phase of the disease (days 6, 9, 12) are
effective to reduce the clinical ocular inflammation and protect
the retinal photoreceptors.
Id. at 22:22-32.
In response to Appellants' contention that it was unexpected that
intravitreal administration of tresperimus improved clinical signs of uveitis
in the rat model, without modification of the systemic immune response, the
Examiner posits that the "response of systemic administration and
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ophthalmic administration locally in the eye are not considered to be the
same. Furthermore, in view of the secondary reference [Renaut], the
ophthalmic administration of the claimed compounds prior to the appellant's
invention is considered to be as old and well know[n]." Ans. 5---6.
The Examiner contends further:
It is the examiner's position that the secondary reference
[Renaut] teaches the ophthalmic use of the claimed compounds.
In the absence of any difference between the claimed
composition and the composition of the secondary reference,
the penetration of the composition of the secondary reference to
the posterior section of the eye flows logically from being the
same composition as the claimed composition.
Id. at 6.
As discussed above, however, while Renaut discloses including its
compounds in eye drop formulations, Renaut does not disclose
administering its eye drops for treating any of the disorders recited in
Appellants' claim 26. We are not persuaded, therefore, that the Examiner's
reliance on the alleged inherent result of Renaut's teachings is sufficient to
rebut the evidence of unexpected results advanced by Appellants.
Moreover, because Renaut does not disclose administering its eye
drops for treating any of the disorders recited in Appellants' claim 26, we
are not persuaded that Appellants failed to compare the claimed process to
the closest prior art. See Millennium Pharmaceuticals, Inc. v. Sandoz, Inc.,
862 F. 3d. 1356, 1368 (Fed Cir. 2017) (An applicant "is not required to
create prior art, nor to prove that his invention would have been obvious if
the prior art were different than it actually was.") ( quotation marks and
citation removed).
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Nonetheless, it is well settled that "[ e ]vidence of secondary
considerations must be reasonably commensurate with the scope of the
claims. . . . This does not mean that an applicant is required to test every
embodiment within the scope of his or her claims." In re Kao, 639 F.3d
1057, 1068 (Fed. Cir. 2011). To the contrary, "[i]f an applicant
demonstrates that an embodiment has an unexpected result and provides an
adequate basis to support the conclusion that other embodiments falling
within the claim will behave in the same manner, this will generally
establish that the evidence is commensurate with scope of the claims." Id.
( emphasis added).
In the present case, as seen above, the evidence advanced to show
unexpected results is limited to the use of a single compound, tresperimus,
whereas claim 26 encompasses a variety of compounds differing
significantly in structure from tresperimus. Compare formula (I) of
Appellants' claim 26 (Br. A-1 (Claims App.)) to Nishi 30:50-56 (structural
formula of tresperimus ). And Appellants identify no specific evidence, in
the Specification or in the form of a declaration, that supports a conclusion
that compounds encompassed by the full breadth of formula (I) would
exhibit the same properties as shown in Appellants' Specification.
Also, we note that claim 26 encompasses any mode of administering
the claimed composition to the eye, whereas the experimental results cited
by Appellants are limited to intravitreal injection. See Spec. 22:8.
Appellants identify no specific evidence, in the Specification or in the form
of a declaration, that supports a conclusion that administering the claimed
compositions by other modes encompassed by claim 26, for example topical
administration, would achieve the same results as shown in Appellants'
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Specification. In that regard, we note the Specification's disclosure that
"[t]he eye is a site of immunological privilege." Id. at 16:34.
In sum, for the reasons discussed, Appellants do not persuade us that
the prior art evidence of obviousness advanced by the Examiner fails to
suggest the process recited in Appellants' claim 26. For the reasons
discussed, we are also not persuaded that the evidence advanced by
Appellants is sufficient to demonstrate that the full scope of the process
recited in claim 26 produces an unexpected result sufficient to outweigh the
prior art evidence of obviousness advanced by the Examiner. Accordingly,
we find that, on the current record, the preponderance of the evidence
supports the Examiner's conclusion of obviousness as to claim 26.
We, therefore, affirm the Examiner's rejection of claim 26 over Nishi
and Renaut. Because they were not argued separately, claims 27-30 and
34--37 fall with claim 26. See 37 C.F.R. § 4I.37(c)(l)(iv).
SUMMARY
For the reasons discussed, we affirm the Examiner's rejection of
claims 26-30 and 34--37 under 35 U.S.C. § 103(a) as being unpatentable
over Nishi and Renaut.
TIME PERIOD
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).
AFFIRMED
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