IRR, Inc.

Patent Trials and Appeals Board

Nov 19, 2021

2021003704 (P.T.A.B. Nov. 19, 2021)

UNITED STATES PATENT AND TRADEMARK OFFICE
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
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
16/587,818 09/30/2019 Bruce Chandler May BCMAY.006C3 9615
20995 7590 11/19/2021
KNOBBE MARTENS OLSON & BEAR LLP
2040 MAIN STREET
FOURTEENTH FLOOR
IRVINE, CA 92614
EXAMINER
BERRIOS, JENNIFER A
ART UNIT PAPER NUMBER
1613
NOTIFICATION DATE DELIVERY MODE
11/19/2021 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):
efiling@knobbe.com
jayna.cartee@knobbe.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte BRUCE CHANDLER MAY
__________

Appeal 2021-003704
Application 16/587,818
Technology Center 1600
__________

Before DONALD E. ADAMS, JEFFREY N. FREDMAN, and
TAWEN CHANG, Administrative Patent Judges.

FREDMAN, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal1 under 35 U.S.C. § 134 involving claims to a method
of reducing the duration of anaphylaxis using an effective amount of a
combination of levocetirizine and montelukast. The Examiner rejected the
claims as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We affirm.

1 We use the word “Appellant” to refer to “applicant” as defined in 37
C.F.R. § 1.42. Appellant identifies the Real Party in Interest as IRR, Inc.
(see Appeal Br. 3). We have considered the Specification of Sept. 30, 2019
(“Spec.”); Final Office Action of Apr. 28, 2020 (“Final Action”); Appeal
Brief of Jan. 27, 2021 (“Appeal Br.”); Examiner’s Answer of Mar. 25, 2021
(“Ans.”); and Reply Brief of May 24, 2021 (“Reply Br.”).
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Statement of the Case
Background
“Levocetirizine is an antihistamine and montelukast is a leukotriene
receptor antagonist” (Spec. ¶ 26). “Levocetirizine, a potent H1-
antihistamine, acts primarily by downregulating the H1 receptor on the
surface of mast cells and basophils to block the IgE-mediated release of
histamine” (id. ¶ 27). “Levocetirizine has been objectively established as
the most potent of the five modem generation antihistamines” (id. ¶ 28).
“Overproduction of leukotriene is a major cause of inflammation”
(Spec. ¶ 30). “Montelukast, a leukotriene receptor antagonist, acts by
binding with high affinity and selectivity to the CysLT1 receptor to inhibit
the physiologic actions of the leukotriene LTD4” (id.). “The two molecules
[levocetirizine and montelukast] are safe, i.e., FDA approved in the United
States for allergic disorders down to age six months. They can be given
primarily or in conjunction with many of the existing therapeutic protocols
for the treatment of inflammation” (id. ¶ 34).
The Claims
Claims 1–5, 11, and 12 are on appeal.2 Claim 1 is an independent
claim, is representative and reads as follows:
1. A method of reducing the duration of anaphylaxis in a
patient in need thereof, comprising administering to the patient
an effective amount of a combination of levocetirizine and
montelukast; wherein the combination is administered at the
onset of symptoms.

2 Claims 6–10 were withdrawn from prosecution (see Amdt. at 3, filed Apr.
16, 2020).
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The Rejection
The Examiner rejected claims 1–5, 11, and 12 under 35 U.S.C.
§ 103(a) as obvious over May3 and Du4 (Final Act. 4–8).
The Examiner finds “May discloses a method of treating
inflammation in a patient in need thereof comprising administering a
combination of levocetirizine and montelukast . . . May teaches that said
combination can be used to prevent or ameliorate the risk of a systemic
reaction [0095]” (Final Act. 6). The Examiner finds May teaches a
“synergistic effect can be observed in the use of a combination of
levocetirizine and montelukast to treat . . . IgE-mediated inflammation” (id.).
The Examiner acknowledges that “May does not teaches [sic] using
levocetirizine and montelukast to reduce the duration of anaphylaxis” (Final
Act. 6). The Examiner finds “Du teaches that acute allergic reactions
including anaphylaxis, is a systemic, immediate hypersensitivity reaction
caused by exposure to a specific antigen. The immune system activates
immunoglobulin E (IgE)” (id. at 7). The Examiner finds it obvious to
use the combination of levocetirizine and montelukast and the
additional active agents as taught by May to treat anaphylaxis
in a patient in need thereof as taught by Du teaches that
levocetirizine can be used to treat anaphylaxis and May teaches
that the combination of levocetirizine and montelukast exhibits
synergistic effects and superior results when used for the
treatment of inflammation, such as those which are IgE-
mediated.
(Id.)

3 May, B., WO 2011/159821 A1, published Dec. 22, 2011.
4 Du, J., US 2012/0053563 A1, published Mar. 1, 2012.
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The Examiner finds “necessarily any patient suffering from
anaphylaxis is in need of a treatment which reduces its duration, therefore
the treatment of said condition is expected to reduce its duration, absent
evidence to the contrary” (Final Act. 8).
The issue with respect to this rejection is: Does a preponderance of
the evidence of record support the Examiner’s conclusion that May and Du
render the claims obvious?
Findings of Fact
1. May teaches “[t]here remains an important unmet need for a
therapeutic approach for . . . acute inflammation” (May ¶ 5).
2. May teaches
the combination of levocetirizine and montelukast as a
medicament for the treatment of acute, subacute and chronic
inflammation. Several embodiments relate to the combination
of levocetirizine and montelukast for the treatment of non-IgE-
mediated, IgE-mediated, and/or combined non-IgE- mediated
and IgE-mediated inflammation.
(May ¶ 58).
3. May teaches “combinations of levocetirizine and montelukast
can be used safely in conjunction with many existing treatment protocols”
(May ¶ 58).
4. May teaches that “[l]evocetirizine is an antihistamine and
montelukast is a leukotriene receptor antagonist. As described herein,
synergy between levocetirizine and montelukast shortens the course of the
disease processes, thereby decreasing morbidity and mortality” (May ¶ 59).
5. May teaches:
This syngergistic effect can be observed in the use of a
combination of levocetirizine and montelukast to treat non-IgE-
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mediated inflammation and combined non-IgE-mediated and
IgE-mediated inflammation. Not wishing to be bound by a
particular theory, the non-IgE-mediated response may be
related, at least in part, to the fact that both levocetirizine and
montelukast affect eosinophil migration.
(May ¶ 59).
6. May teaches “levocetirizine has been shown to decrease
eosinophil migration and decrease inflammatory mediators, IL-4, IL-6, and
IL-8. IL-6, a signaling protein, regulates in part: fever, the body’s response
to trauma, and the acute (immediate) phase of the allergic reaction” (May
¶ 62).
7. May teaches dosages for treatment of allergic disorders in Table
V, reproduced below:

“Table V shows the existing country guidelines for dosages in the treatment
of allergic disorders” (May ¶ 88).
8. May teaches the “two molecules [levocetirizine and
montelukast] are safe, i.e., FDA approved in the United States for allergic
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disorders down to age six months. They can be given primarily or in
conjunction with many of the existing therapeutic protocols for the treatment
of inflammation” (May ¶ 67).
9. May teaches “montelukast and levocetirizine treatment reduces
the duration of influenza. In some embodiments, montelukast and
levocetirizine treatment reduces the severity of influenza symptoms” (May
¶ 80). May also teaches “montelukast and levocetirizine treatment reduces
the duration of the cold. In some embodiments, montelukast and
levocetirizine treatment reduces the severity of cold symptoms” (id.).
10. Du teaches “[a]cute allergic reaction including anaphylaxis, is a
systemic, immediate hypersensitivity reaction caused by exposure to a
specific antigen. The immune system activates immunoglobulin E (IgE),
which reacts with effector cells (mast cells and basophils)” (Du ¶ 2).
11. Du teaches, Table 2, that levocetirizine is a third generation
antihistamine and teaches “injectable formulations of second and third
generation antihistamines, or non-sedating antihistamines, via intravenous,
intramuscular, or subcutaneous administration to provide an immediate onset
of action. Such second and third generation antihistamines are commercially
available” (Du ¶ 33).
12. Du teaches “methods of treating an acute allergic reaction
including anaphylaxis comprising administering to an individual in need
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thereof an effective amount of an injectable composition comprising a
second or third generation antihistamine” (Du ¶ 49).
13. Du teaches that levocetirizine in amounts of 2.5 mg and 5 mg is
a known second or third generation antihistamine (Du ¶ 47).
14. Du teaches that current anaphylaxis treatment uses epinephrine
which, among other activities, “suppresses histamine and leukotriene
release, reducing inflammatory responses” (Du ¶ 6).
15. Du teaches the “methods described herein optionally further
comprise administering a second active agent as well as the second or third
generation antihistamine” (Du ¶ 55).
Principles of Law
The Examiner has the initial burden of establishing a prima facie case
of obviousness under 35 U.S.C. § 103. In re Oetiker, 977 F.2d 1443, 1445
(Fed. Cir. 1992). “The combination of familiar elements according to
known methods is likely to be obvious when it does no more than yield
predictable results.” KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416
(2007).
Analysis
We adopt the Examiner’s findings of fact and conclusion of law (see
Final Act. 4–6; FF 1–15) and agree that May and Du renders the claims
obvious.
In particular, we agree with the Examiner that Du directly suggests
treatment of acute inflammatory diseases caused by activation of IgE (FF
10) such as anaphylaxis (FF 12) with a second or third generation
antihistamine such as levocetirizine (FF 13). Du teaches administration of a
second active agent (FF 15) and recognizes that current anaphylaxis
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treatments function to inhibit leukotriene release to reduce the inflammatory
response (FF 14).
We agree that May teaches the combination of the antihistamine
levocetirizine and leukotriene antagonist montelukast (FF 4). May teaches
that this combination of compounds shows synergy that “shortens the course
of the disease processes” to treat IgE mediated processes (FF 4–5). May
teaches the use of doses (FF 7) identical to those recited in the Specification
(Spec. ¶ 55). May exemplifies this combination as reducing duration of
several diseases (FF 9).
We agree with the Examiner that the combination of Du and May
would have been obvious because “Du teaches that levocetirizine can be
used to treat anaphylaxis and May teaches that the combination of
levocetirizine and montelukast exhibits synergistic effects and superior
results when used for the treatment of inflammation, such as those which are
IgE-mediated” (Ans. 5).
We address Appellant’s arguments below.
Appellant contends it is “undisputed that the May Publication fails to
teach the treatment of ‘anaphylaxis,’ much less ‘reducing the duration of
anaphylaxis,’ as recited in Claim 1” (Appeal Br. 5) (emphasis omitted).
Appellant also contends “Du should [sic] does not and should not be
assumed to teach any reduction in the duration of anaphylaxis using an
antihistamine” (id. at 6). Appellant cites the May Declaration,5 where Dr.
May states “the treatment of symptoms of anaphylaxis would not have been

5 Declaration of Dr. Bruce C. May, dated March 11, 2019.
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understood by a person of ordinary skill in the art as reducing the duration
of anaphylaxis” (May Decl. ¶ 9; cf. Appeal Br. 6–7).
We find these arguments unpersuasive for a number of reasons. First,
the combination of Du and May suggest administration of the same dosages
of the same drugs (FF 7; Spec. ¶ 55) to the same patient population with
anaphylaxis (FF 12) for treatment of the same IgE inflammatory response
(FF 1, 2, 5, 8, 10–15; cf. Spec. ¶ 67). Thus, we agree with the Examiner’s
inherency reasoning (Ans. 7) consistent with King Pharm. Inc. v. Eon Labs,
Inc., 616 F.3d 1267, 1276 (Fed. Cir. 2010), because “the prior art need only
meet the inherently disclosed limitation to the extent the patented method
does.” Montgomery explains that in King,
one of the claims covered “a method of increasing the oral
bioavailability of metaxalone” by “administering to the patient
a therapeutically effective amount of metaxalone in a
pharmaceutical composition with food.” We noted that
according to the patent itself, “the natural result of taking
metaxalone with food is an increase in the bioavailability of the
drug,” and that “[t]he prior art discloses taking metaxalone with
food,” so the preamble was “inherently anticipated.”
In re Montgomery, 677 F.3d 1375, 1381 (Fed. Cir. 2012) (citing King, 616
F.3d at 1275–76. As we compare King to the instant situation, we find that
to the extent that the natural result of taking levocetirizine and montelukast
for anaphylaxis would be to reduce the duration of anaphylaxis, the same
result would be inherent for the combination of Du and May.
Second, May expressly teaches that the combination of levocetirizine
and montelukast shows synergy and “shortens the course of the disease
processes, thereby decreasing morbidity and mortality” (FF 4). May further
teaches “montelukast and levocetirizine treatment reduces the duration of
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influenza” and colds (FF 9). Thus, as we balance these teachings in May
with the May Declaration paragraph 9, we find that the ordinary artisan
would have reasonably interpreted May as suggesting the combination
would have been expected to reduce the duration of disease.
Third, we also are not persuaded by the May Declaration paragraphs 9
and 11 that treatment of anaphylaxis in particular would not also necessarily
reduce the duration of anaphylaxis. Du teaches levocetirizine treatment of
anaphylaxis would have been expected to “provide an immediate onset of
action” (FF 11) and would be expected to reduce inflammatory response (FF
14). Because anaphylaxis is an acute life-threatening immune response and
May and Du both teach treatment of such acute immune responses with
these drugs (FF 2, 10, 12) to mitigate the threat to a patient’s life, we agree
with the Examiner that the ordinary artisan would interpret May and Du as
reducing the duration of anaphylaxis (see Ans. 8).
Appellant contends “Du does not disclose the use of any non-sedating
antihistamine for the treatment of anaphylaxis itself, much less the duration
of anaphylaxis, as recited in Claim 1” (Appeal Br. 7). Appellant further
contends
one of ordinary skill would not understand that the use of
antihistamines in Du meant treating the underlying disease state
of anaphylaxis itself, much less that it meant “reducing the
duration of anaphylaxis,” as recited in Claim 1. . . .
Accordingly, because Du is missing at least this limitation, for
at least this reason, the prima facie case has not been
established.
(id. at 8).
We find these arguments unpersuasive because the rejection is based
on the combination of Du and May, not Du alone. “Non-obviousness cannot
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be established by attacking references individually where the rejection is
based upon the teachings of a combination of references. . . . [The
reference] must be read, not in isolation, but for what it fairly teaches in
combination with the prior art as a whole.” In re Merck & Co., 800 F.2d
1091, 1097 (Fed. Cir. 1986). Moreover, we find that Du’s teaching of
immediate onset of action (FF 11) to mitigate the threat of death from
anaphylactic shock would have been reasonably understood as a treatment
that reduces the duration of anaphylaxis to prevent death from anaphylactic
shock, not just as mitigating the symptoms. While the May Declaration
asserts “symptomatic treatment (e.g., the treatment of symptoms) disclosed
in Du is different from treating an underlying disease state” (May Decl. ¶ 9),
Dr. May does not explain how Du’s immediate acting treatment of
anaphylaxis fails to reduce the duration of such anaphylaxis.
Appellant cites Kronenberg6 as a reference that “discusses the
difference between the treatment of symptoms (e.g., ‘symptomatic’
treatment) and the treatment of an underlying disease state” (Appeal Br. 8;
citing Kronenberg 9; cf. May Decl. ¶¶ 10–11). Appellant contends that,
“[j]ust as Kronenberg discloses that a symptomatic treatment does not affect
the underlying disease state, so too would one of ordinary skill understand
the disclosure of Du to be the treatment of symptoms and not the treatment
of the underlying anaphylaxis that causes those symptoms” (id. at 9).

6 Andreas Kronenberg et al., Symptomatic treatment of uncomplicated lower
urinary tract infections in the ambulatory setting: randomised, double blind
trial, 359 BMJ 1–10 (2017).
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We find this argument unpersuasive because Kronenberg is not drawn
to the same type of disease as the immune-modulated diseases such as
anaphylaxis disclosed by Du and May, but rather is drawn to lower urinary
tract infections (see Kronenberg 1). Indeed, Kronenberg contradicts
Appellant’s point by teaching that antibiotic treatment of the underlying
disease was superior to symptom control (see Kronenberg 6, col. 2
“symptomatic treatment with the non-steroidal anti-inflammatory drug
(NSAID) diclofenac was inferior to antibiotic treatment with norfloxacin in
controlling symptoms.”) Kronenberg concludes: “Symptomatic treatment is
inferior to antibiotic treatment for women with uncomplicated lower UTI in
an ambulatory setting” (Kronenberg 9).
And in the particular context of treatment of anaphylaxis, an
immediate hypersensitivity reaction modulated by IgE, both Du and May
suggest that anti-histamines treat the underlying condition of IgE mediated
inflammation (FF 2, 12). As already noted, May expressly teaches that the
combination of levocetirizine and montelukast reduces the duration of IgE
mediated inflammation (FF 4, 5, 9).
Appellant contends
one of ordinary skill in the art would have understood that the
non-sedating antihistamines of Du were used as treatments for
symptoms of anaphylaxis. Because Du discloses epinephrine as
the only “first-line” drug for treating anaphylaxis and
antihistamines as “second-line” drugs only for the treatment of
symptoms, one of ordinary skill in the art would have lacked
any reasonable expectation of success.
(Appeal Br. 10).
We do not find these arguments persuasive because both May and Du
specifically suggest that the methods will be useful in treatment of acute
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inflammation (FF 2, 5, 6, 9) and anaphylaxis in particular (FF 12–15).
Indeed, May teaches a number of working examples where the combination
of levocetirizine and montelukast results in synergistic treatment of different
diseases (May ¶¶ 105–160) and Du expressly suggests “methods of treating
an acute allergic reaction including anaphylaxis comprising administering to
an individual in need thereof an effective amount of an injectable
composition comprising a second or third generation antihistamine” (FF 12).
This is neither a case of throwing darts, as the prior art provides
specific doses of specific medications in a specific patient population, nor is
this a case of varying a variety of parameters without knowledge of which
were critical. Instead, the rejection relies in part upon a combination of
working examples in May and an express teaching in Du to provide
substantial evidence supporting a reasonable expectation of success in
reducing the duration of anaphylaxis as desired by Du using the synergistic
composition of levocetirizine and montelukast disclosed by May.
“Obviousness does not require absolute predictability of success . . . all that
is required is a reasonable expectation of success.” In re Kubin, 561 F.3d
1351, 1360 (Fed. Cir. 2009) (emphasis omitted).
In the Reply Brief, Appellant acknowledges that “the Federal Circuit
recently held that, under specific factual circumstances, two prior art
references may be combined to find inherency through obviousness” (Reply
Br. 5; citing Persion Pharm., LLC. v Alvogen Malta Operations Ltd., 945
F.3d 1184 (Fed. Cir. 2019). Appellant attempts to distinguish Persion (as
well as a number of other cases such as Montgomery, King, and PAR
Pharm., Inc. v. TWI Pharm., Inc., 773 F.3d 1186 (Fed. Cir. 2014) among
others), by contending that unlike Persion, “Du fails [to] disclose the
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combination recited in Claim 1, much less ‘[a] method of reducing the
duration of anaphylaxis in a patient,’” that “the May Publication is silent as
to anaphylaxis,” and that “neither Du nor the May Publication disclose
actual administration to the claimed patient population, those with
anaphylaxis” (Reply Br. 6) (emphasis omitted).
We find this argument unpersuasive because Montgomery explains, in
the anticipation context, that a mere proposal without working examples
would still anticipate. Montgomery, 677 F.3d at 1382. And Persion teaches
“[i]t is long settled that in the context of obviousness, the ‘mere recitation of
a newly discovered function or property, inherently possessed by things in
the prior art, does not distinguish a claim drawn to those things from the
prior art.’” Persion, 945 F.3d at 1190 (citing In re Oelrich, 666 F.2d 578,
581 (CCPA 1981). In the instant situation, efficacy of May’s synergistic
composition of levocetirizine and montelukast was inherent for use in IgE
mediated disease on IgE mediated anaphylaxis as disclosed by Du, where
Du suggests treatment of anaphylaxis using levocetirizine and additional
agents (FF 1–15). The efficacy of this combination on reduced duration of
anaphylaxis represents an inherent result necessarily possessed when the
same dosage of levocetirizine and montelukast would be administered to the
same patient population. “[A] newly-discovered result or property of an
existing (or obvious) method of use is not patentable.” Allergan, Inc. v.
Sandoz Inc., 726 F.3d 1286, 1296 (Fed. Cir. 2013) (emphasis omitted).
Conclusion of Law
A preponderance of the evidence of record supports the Examiner’s
conclusion that May and Du render the claims obvious.

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DECISION SUMMARY
In summary:
Claim(s)
Rejected
35 U.S.C. §  Reference(s)/Basis Affirmed Reversed
1–5, 11, 12 103  May, Du 1–5, 11, 12

No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a). See 37 C.F.R.
§ 1.136(a)(1)(iv).

AFFIRMED