Ex Parte Aberg et al

Patent Trial and Appeal Board

Jun 27, 2018

13744807 (P.T.A.B. Jun. 27, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
13/744,807 01/18/2013
23413 7590 06/29/2018
CANTOR COLBURN LLP
20 Church Street
22nd Floor
Hartford, CT 06103
FIRST NAMED INVENTOR
A.K. Gunnar Aberg
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.
BPI0002US2 1138
EXAMINER
STRONG, TORI
ART UNIT PAPER NUMBER
1629
NOTIFICATION DATE DELIVERY MODE
06/29/2018 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):
usptopatentmail@cantorcolbum.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte A.K. GUNNAR ABERG and VINCENT B. CIOF ALO
Appeal2015-000463
Application 13/744,807 1
Technology Center 1600
Before DONALD E. ADAMS, ERIC B. GRIMES, and
SHELDON M. McGEE, Administrative Patent Judges.
McGEE, Administrative Patent Judge.
DECISION ON APPEAL
Pursuant to 35 U.S.C. § 134, Appellant seeks our review of the
Examiner's rejection of claims 1-3, 6-10, and 16-23.
We have jurisdiction. 35 U.S.C. § 6.
We affirm.
1 Appellant is the Applicant, Bridge Pharma, Inc., which is also identified as
the real party in interest. Appeal Br. 2.
Appeal2015-000463
Application 13/744,807
SUBJECT MATTER
Appellant claims methods for treating chronic atopic inflammatory
dermal disorders, and methods of reducing sedative side effects in the
treatment of such disorders, in a human patient, comprising orally
administering racemic norketotifen2 at a dosage of between 0.5 to 20 mg
once or more daily, wherein such administration does not produce a sedative
side effect in the patient. Claims 1, 16.
Appellant also claims a method for treating chronic atopic
inflammatory dermal disorders in a human patient, where it is first
determined whether the patient is susceptible to adverse sedative effects of
an antihistamine compound, and if such determination is positive, an oral
formulation of 0. 5 to 2 0 mg of racemic norketotifen is administered once or
more daily. Claim 17.
A copy of representative claim 1, taken from the Claims Appendix of
the Appeal Brief, appears below.
1. A method for treating chronic atopic inflammatory
dermal disorders in a human patient in need thereof,
comprising orally administering to the human patient with a
chronic atopic inflammatory dermal disorder a therapeutically
effective amount of RS-norketotifen or a pharmaceutically
acceptable salt thereof, wherein the therapeutically effective
amount of RS-norketotifen or a pharmaceutically acceptable
salt thereof is 0.5 to 20 mg dosed once or more daily, and
wherein the therapeutically effective amount of RS-
norketotifen does not produce sedative side effects in the
human patient.
2 According to i-fl2 of Appellant's Specification, racemic norketotifen is also
known as RS-norketotifen, nor-ketotifen, and norketotifen.
2
Appeal2015-000463
Application 13/744,807
STATEMENT OF THE CASE
The Examiner rejects claims 1-3, 6-10, and 16-23 under 35 U.S.C.
§ 103(a) as unpatentable over Aberg, et al. ("Aberg", US 7,226,934 Bl,
issued June 5, 2007). Final3 3; Ans. 3.
The Examiner finds that Aberg teaches using racemic norketotifen to
treat inflammatory disorders, including inflammatory atopic dermal
disorders, and that such treatment is devoid of sedative side effects. Final 6.
The Examiner finds further that Aberg teaches multiple routes of
administration, including oral administration and further teaches an oral
dosage and frequency embodiment that encompasses 0.5 mg to 20 mg given
daily. Final 6-7.
The Examiner finds that "[ w ]hile Aberg does not explicitly state
chronic atopic inflammatory dermal disorders ... Aberg exemplifies
diseases such as atopic dermatitis and psoriasis ... which are known chronic
disorders" and are encompassed by the disorders recited in the claims.
Final 7. The Examiner also finds that Aberg evinces very limited sedative
side effects occurring in a mouse model when racemic norketotifen was
administered, and determines that one of ordinary skill would have utilized
such information in Aberg "to investigate whether the ... limiting to no
sedative side effects ... would transfer to a human patient population having
a reasonable expectation of success." Final 7.
The Examiner concludes that because "[t]he instant invention utilizes
the same range of dosing from the prior art and demonstrated no sedative
side effects in humans," it would have been "prima facie obvious to one of
3 Office Action dated Feb. 19, 2014.
3
Appeal2015-000463
Application 13/744,807
ordinary skill in the art at the time of invention to treat chronic atopic
inflammatory dermal disorders with racemic norketotifen in the range of 0.5
to 20 mg while expecting no sedative side effects." Final 7-8.
OPINION
Appellant argues the patentability of claims 1-3, 6-10, and 16-23 as a
group. Appeal Br. 3-14; Reply Br. 3-19. We therefore select claim 1 as
representative and decide this appeal on the basis of claim 1 alone.
37 C.F.R. § 41.37(c)(l)(iv).
Appellant contends that the Aberg reference does not teach the
limitations "as arranged in the claims" as would be required for a rejection
under 35 U.S.C. § 102(b). Appeal Br. 6. Thus, Appellant faults the
Examiner's obviousness rejection because "the claim elements must be
assembled from different places within the Aberg reference and with
significant extrapolation from [Aberg's] disclosure." Appeal Br. 6. This
argument, without more, fails to identify reversible error in the rejection
because it is conclusory and also does not address the Examiner's specific
findings regarding Aberg. Moreover, "the mere existence of differences
between the prior art and an invention does not establish the invention's
nonobviousness." Dann v. Johnston, 425 U.S. 219, 230 (1976).
Appellant argues further that the skilled artisan "would not have been
motivated to study the effect of norketotifen on sedation in humans" because
a significant sedative effect would have been expected in humans "based on
the previous results that consistently demonstrated sedation ... in the art-
accepted mouse model." Appeal Br. 6-7. In support of this contention,
Appellant refers to Declaration evidence that, according to Appellant,
demonstrates that "norketotifen was 6-7 times less sedating than ketotifen in
4
Appeal2015-000463
Application 13/744,807
the mouse studies," and, assuming the dose-response curves in mice are
identical to those in humans, "a dose of 6-7 mg of RS-norketotifen would
produce the same, very significant sedative side effects in adult human
subjects as ketotifen in a dose of 1 mg." Reply Br. 8.
This line of argument is unpersuasive because it does not squarely
address the Examiner's rejection. Here, we agree with the Examiner (Final
4) that such arguments misunderstand the underlying basis for the rejection
and ignore the scope and content of Aberg's teaching at column 3, lines 19-
22 ("[i]t has now also been established that racemic norketotifen ... has
potent anti-inflammatory and anti-histaminic properties with little or no
sedative side effect."). Based on this disclosure, the skilled artisan would
have had a reasonable expectation that racemic norketotifen would exhibit
these properties in a human population - particular I y in view of Aberg' s
disclosure that norketotifen may be administered to "mammals, such as
humans" to treat a variety of disorders "while avoiding ... sedation and
other toxic manifestations of ketotifen and steroids." Aberg 13:30-66.
Moreover, as correctly explained by the Examiner (Ans. 7),
Appellant's claims include dosages of 0.5 to 5.0 mg, which are lower than
the 6-7 mg dose Appellant argues would be expected to produce sedation in
humans. Appellant has not demonstrated that a person of ordinary skill
would not have been motivated to study the effects of norketotifen on
sedation in humans, or otherwise treat the recited disorders, at the claimed
doses which fall below 6-7 mg. We furthermore agree with the Examiner
that, "[ w ]hile there was no established guarantee of success of predicting no
sedation in humans with administration of racemic norketotifen," only a
reasonable expectation of success is necessary to establish a prima facie case
5
Appeal2015-000463
Application 13/744,807
of obviousness. Ans. 7; Final 5---6. "Obviousness does not require absolute
predictability of success .... For obviousness under§ 103, all that is
required is a reasonable expectation of success." In re 0 'Farrell, 853 F.2d
894, 903---04 (Fed. Cir. 1988).
Appellant contends further that Aberg' s disclosure that "racemic
norketotifen ... has ... little or no sedative side effect" should be read as
only relative to ketotifen. Appeal Br. 7-8. Specifically, Appellant asserts
that "[ w ]hile Aberg states that racemic norketotifen was 'devoid of the
severe dose-limiting sedative side effects of ketotifen', there is absolutely no
suggestion in Aberg that norketotifen is non-sedative." Reply Br. 7.
We are not persuaded that Aberg's teaching regarding the sedative
side effect of norketotifen is limited to a comparison with only ketotifen, as
argued by Appellant. In particular, the disclosure relied on by the Examiner
appears under the "Summary of the Invention" heading in column 3 of
Aberg, which recites, in relevant part:
Various metabolites of ketotifen have ... been synthesized and
studied pharmacologically. It has been found that the
antihistaminic effects of racemic norketotifen are qualitatively
similar to the antihistaminic effects of racemic ketotifen. . . .
However, surprisingly and importantly, a significant qualitative
difference was found between racemic ketotifen and the
compounds described in this invention: the compounds
described here do not have the severe and dose-limiting sedative
activity of ketotifen. It has now also been established that
racemic norketotifen and particularly the isomer thereof has
potent anti-inflammatory and anti-histaminic properties with
little or no sedative side effect. Likewise, it was found that
while both isomers of ketotifen had approximately the same
antihistaminic activity, almost all the sedative side effects were
found to reside in R( + )-ketotifen. The metabolites of 10-
hydroxy-norketotifen and 10-hydroxy-ketotifen and the isomers
6
Appeal2015-000463
Application 13/744,807
of both compounds were also found to inhibit inflammation and
to block histamine H-1 receptors, while causing significantly
less sedation than ketotifen.
(Aberg, 3 :8-30, emphases added).
In the above passage, Aberg broadly compares the sedative side
effects of the "compounds described in this invention" to ketotifen. Such
compounds of the invention include "nor-ketotifen, 10-hydroxy-ketotifen,
10-hydroxy-norketotifen, or optically active isomers of ketotifen,
norketotifen, 10-hydroxy-ketotifen or 10-hydroxy-norketotifen, and
pharmaceutically acceptable salts and solvates thereof." Aberg, 1: 12-16.
Aberg, however, further distinguishes the sedative side effects observed with
"racemic norketotifen and the isomer thereof' (i.e., "little or no sedative side
effect") with those observed with "10-hydroxy-norketotifen and 10-hydroxy-
ketotifen and the isomers of both compounds" (i.e., "significantly less
sedation than ketotifen"). Id. at 3:20-30. In other words, Aberg indeed
compares the sedative side effects of the claimed racemic norketotifen, as
one of the "compounds described in this invention," and finds them to be
less "severe and dose-limiting" than the sedative side effects of ketotifen.
Id. at 3:15-19. However, Aberg goes one step further when he states that
"[i]t has now also been established that racemic norketotifen ... has potent
anti-inflammatory and anti-histaminic properties with little or no sedative
side effect." Id. at 3:20-22 (emphasis added). Additionally, we note that
Aberg discloses methods of treating inflammatory and allergic diseases,
including skin disorders by using norketotifen "while avoiding sedative
and cardiovascular side effects that are commonly associated with
antihistamines." Id. at 1 :9-24. In this passage, Aberg does not limit his
7
Appeal2015-000463
Application 13/744,807
comparison of the sedative side effects of norketotifen to ketotifen. Rather,
Aberg indicates the sedative side effects germane to antihistamines are
avoided. Id. at 1:21-23.
Thus, because Aberg' s disclosure goes beyond a simple comparison
of racemic norketotifen's sedative side effects relative to ketotifen, we
decline to read Aberg' s disclosure as narrowly as Appellant urges. "It is
well settled that a prior art reference is relevant for all that it teaches to those
of ordinary skill in the art." In re Fritch, 972 F.2d 1260, 1264 (Fed. Cir.
1992).
Appellant further argues that, because it is not possible for the same
compound to have "little or no" sedative side effects, "either [the compound]
has sedative side effects, or it does not." Appeal Br. 8. We are not
persuaded by this argument because Appellant cites to no scientific evidence
to support this assertion. Moreover, Appellant's argument contradicts
several statements (and data) contained in the Specification which suggest
that the sedative side effects of a particular compound depend on whether it
is administered to "a human patient [that is] susceptible to adverse sedative
effects of compounds" (Spec. i-f 8), and the dosage at which it is given (Spec.
,-r,-r 14, 55, 59).
Appellant further argues that Aberg only teaches topical
administration of racemic norketotifen in the treatment of dermal disorders.
We agree with the Examiner that this argument is technically erroneous, and
therefore unpersuasive, because Aberg teaches systemic administration
(intraperitoneal (ip) injection) specifically to demonstrate dermal anti-
inflammatory effects ( Aberg 9: 1-19), and furthermore "provides explicit
guidance for oral administration," without limiting the disorders for which
8
Appeal2015-000463
Application 13/744,807
oral administration is appropriate. Ans. 9-10. Appellant's response that
Aberg's injection formulation was merely a prophetic example and "a test
study performed in mice" (Reply Br. 13) does not negate Aberg's explicit
disclosure regarding oral administration forms. Aberg, 9 :49---63, 10: 5--4 7.
Finally, Appellant alleges that "[b]ased on the teaching of the Aberg
reference and the totality of the prior art ... it is not reasonable to expect no
sedative effects for racemic norketotifen" in the human population. Appeal
Br. 10. Rather, Appellant contends that, based on data contained in the
Specification and the Third Aberg Declaration, 4 it was unexpectedly
discovered that racemic norketotifen is non-sedating in humans. Id. at 10-
12; Reply Br. 17.
For several reasons, we are not persuaded by Appellant's arguments
alleging unexpected results. First, we emphasize Aberg's explicit teaching
that "racemic norketotifen and particularly the isomer thereof has potent
anti-inflammatory and anti-histaminic properties with little or no sedative
side effect" (Aberg, 3: 19-22, emphasis added). "[A] prior art publication
cited by an Examiner is presumptively enabling barring any showing to the
contrary by a patent applicant." In re Antor Media Corp., 689 F.3d 1282,
1288 (Fed. Cir. 2012). Here, Appellant has made no such showing
sufficiently challenging the enablement of the Aberg reference.
Furthermore, Aberg discloses that a preferred oral dose of
norketotifen in treating inflammatory airway disorders or a seasonal allergic
condition is from 1.0 to 20 mg. See, Aberg, 12:36-50. While we recognize
4 Declaration under 37 C.F.R. § 1.132 of A.K. Gunnar Aberg, dated Jan. 14,
2014.
9
Appeal2015-000463
Application 13/744,807
Appellant's claims are directed to treating inflammatory dermal (i.e., not
airway or seasonal allergy) disorders, a person of ordinary skill would have
reasonably expected no sedative side effects to be exhibited in a human
patient upon administering racemic norketotifen at the claimed dosages, and
particularly at the lowest dosage disclosed for an inflammatory airway
disorder, i.e., 0.5 mg. Thus, the skilled artisan would have reasonably
expected the result that Appellant avers is unexpected, and "[ e ]xpected
beneficial results are evidence of obviousness." In re Skoner, 517 F.2d 947,
950 (CCPA 1975).
We also note that "objective evidence of non-obviousness must be
commensurate in scope with the claims which the evidence is offered to
support." In re Tiffin, 448 F.2d 791, 792 (CCPA 1971). Here, Appellant's
claim 1 encompasses dosages of 0.5 to 20 mg of racemic norketotifen dosed
once or more daily. However, Appellant has not provided any evidence
which shows that one or more 20 mg dose does not produce sedative side
effects in humans. Accordingly, Appellant's evidence is not commensurate
in scope with the dose ranges recited in claim 1.
DECISION
The Examiner's obviousness rejection of claims 1-3, 6-10, and 16-23
as obvious over Aberg is sustained for the reasons expressed by the
Examiner and above.
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
10