Ex Parte Sipka et al

Board of Patent Appeals and Interferences

Jun 11, 2012

10651136 (B.P.A.I. Jun. 11, 2012)

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.
10/651,136 08/28/2003 Sandor Sipka 22740-2 8175
24256 7590 06/11/2012
DINSMORE & SHOHL LLP
1900 CHEMED CENTER
255 EAST FIFTH STREET
CINCINNATI, OH 45202
EXAMINER
ROONEY, NORA MAUREEN
ART UNIT PAPER NUMBER
1644
MAIL DATE DELIVERY MODE
06/11/2012 PAPER
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.
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte SANDOR SIPKA, LORAND BERTOK,
GEZA BRUCKNER, and SCHNITZER FERENC
__________

Appeal 2011-007060
Application 10/651,136
Technology Center 1600
__________

Before TONI R. SCHEINER, MELANIE L. McCOLLUM, and
JEFFREY N. FREDMAN, Administrative Patent Judges.

McCOLLUM, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a process
for decreasing allergic asthma development. The Examiner has rejected the
claims as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We affirm-
in-part.
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Application 10/651,136

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STATEMENT OF THE CASE
Claims 1-3, 5, 10, 13, 17, 18, and 22-25 are on appeal (App. Br. 2).1
We will focus on claims 1, 22, and 25, the only independent claims on
appeal, which read as follows:
1. A process for decreasing development of allergic asthma, the
process comprising exposing a neonatal or immature mammal to irradiation-
detoxified lipopolysaccharide (IR-LPS) derived from extracted bacterial
endotoxin and operable to stimulate the Th 1 arm of the mammal’s immune
system, wherein exposure comprises at least weekly administration during
maturation of the mammal via application of the IR-LPS to a living
environment of the mammal.
22. A process for decreasing development of allergic asthma in a
mammal maturing in an overly sterile environment by restoring normal
immune system development, the process comprising exposing a neonatal or
immature mammal to irradiation-detoxified lipopolysaccharide derived from
extracted E. coli bacteria endotoxin and operable to stimulate the Th 1 arm
of the mammal’s immune system, wherein exposure occurs via
administration of the IR-LPS during maturation of the mammal.
25. A process for decreasing development of allergic asthma, the
process comprising exposing a neonatal or immature human of up to about
2 years of age to irradiation-detoxified lipopolysaccharide derived from
extracted bacterial endotoxin and operable to stimulate the Th 1 arm of the
human’s immune system while reducing interleukin 1(IL-1) stimulation
caused by the native form of the lipopolysaccharide derived from extracted
bacterial endotoxin, wherein exposure comprises administration on an at
least weekly basis of an aerosol spray composition comprising the
irradiation-detoxified lipopolysaccharide at a concentration of 5-15 µg/ml.

1 Claims 6-9, 11, 12, 14-16, 20, and 21 are also pending but have been
withdrawn from consideration (App. Br. 1).
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Claims 1-3, 5, 10, 13, 17, 18, and 22-25 stand rejected under
35 U.S.C. § 103(a) as obvious over Cochran2 in view of Previte3 and
Baldridge4 (Ans. 3).
Claims 1-3, 5, 10, 13, 17, 18, and 22-25 stand rejected under
35 U.S.C. § 103(a) as obvious over Khan5 in view of Previte and Baldridge
(Ans. 8).
I
The Examiner relies on Cochran for teaching:
A process for decreasing development of allergic asthma (OVA
induced asthma) comprising exposing an infant, neonatal or
immature mammal maturing in an overly sterile environment
shortly after birth (2-3 week old laboratory mice) to
lipopolysaccharide derived from extracted bacterial endotoxin
(E.coli LPS) by administering an aerosol spray composition of
the mammal to a living environment/space (saline and air
during nasal aspiration) during maturation of the mammal (at 2-
3 weeks) . . . .
(Ans. 3.) In particular, the Examiner finds:

2 John R. Cochran et al., Influence of Lipopolysaccharide Exposure on
Airway Function and Allergic Responses in Developing Mice, 34 PEDIATRIC
PULMONOLOGY 267-277 (2002).
3 Joseph J. Previte et al., Detoxification on Salmonella typhimurium
Lipopolysaccharide by Ionizing Radiation, 93 JOURNAL OF BACTERIOLOGY
1607-1614 (1967).
4 Jory R. Baldridge et al., Monophosphoryl lipid A enhances mucosal and
systemic immunity to vaccine antigens following intranasal administration,
18 VACCINE 2416-2425 (2000).
5 Amir M. Khan et al., Functional and Immune Response to
Lipopolysaccharide and Allergens in Developing Mice, PEDIATRIC
RESEARCH, vol. 51, Abstract 2766 (2002).
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Cochran . . . teaches that “recent studies raised the intriguing
hypothesis that exposure to LPS may interact with the immune
system in early life and produce a protective environment
against the development of asthma and atopy. Despite the
potential importance of this phenomenon in the pathogenesis of
childhood asthma, only recently have animal models been used
to study the interactions between endotoxin and allergic
responses as a function of age” and “patients become
symptomatic in their first 5 years of life” (In particular,
page 268, left column).
(Ans. 3-4.)
The Examiner relies on Previte for teaching “the detoxification of
isolated LPS of S. typhimurium, S. enteritidis and E. coli using 4, 4.8 and
4.5 Mrad (about 25 to about 150 kGy) ionizing radiation” (id. at 5). The
Examiner finds that the “detoxification eliminates lethality induced by its
lethal determinants (changes the structure), while retaining antigenticity [sic]
(maintaining its Th1 stimulatory effect ) and pyrogenicity” (id.). The
Examiner concludes that it would have been “obvious to use a safer, less
toxic form of LPS in neonatal or immature mammals to decrease allergic
asthma” (id. at 7).
The Examiner relies on Baldridge for teaching “the weekly intranasal
vaccination of mice with the adjuvant monophosphoryl lipid A (MPL),
which is derived from lipopolysaccharide and has retained immuno-
stimulatory properties and decreased toxicity, resulting in increased Th1
responses” (id. at 5). The Examiner concludes that it “would have been
obvious to administer the detoxified LPS at least weekly because Baldridge
et al. teaches that the weekly intranasal administration of the detoxified LPS
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adjuvant monophosphoryl lipid A results in the generation of a Th1
response” (id. at 7).
Analysis
Appellants argue that “the combination of Cochran, Previte, and
Baldridge fails to teach or suggest the limitation ‘to a living environment of
the mammal’” (App. Br. 15-16). We agree.
Claim 1 recites that the exposure to IR-LPS comprises administration
“via application of the IR-LPS to a living environment of the mammal.” We
agree with Appellants that this language requires application “to the
environment external to the mammal - - that is, the mammal’s external living
surroundings” (App. Br. 15). The Examiner finds that this definition “is not
supported by the facts,” noting that “arguments of counsel cannot take the
place of evidence in the record” (Ans. 19). However, the Specification
supports Appellants’ interpretation, stating that “the exposure may be
achieved by administering an aerosol spray composition comprising the
irradiation-detoxified lipopolysaccharide to surrounding environment or
directly to the subject” (Spec. 6-7 (emphasis added)). Thus, we do not agree
with the Examiner that Appellants’ definition is not supported by the facts.
Both of Cochran and Baldridge disclose intranasal administration
(Cochran 267: Abstract & Baldridge 2416: Abstract). Previte discloses
intraperitoneal administration (Previte 1607). The Examiner has not set
forth a prima facie case that it would have been obvious to instead
administer the LPS “via application . . . to a living environment of the
mammal,” as recited in claim 1. We therefore reverse the obviousness
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rejection over Cochran, Previte, and Baldridge of claim 1 and of claims 2, 3,
5, 10, 13, 17, and 18, which depend from claim 1.
However, neither of claims 22 and 25 requires administration “via
application of the IR-LPS to a living environment of the mammal.” Thus,
this argument does not apply to claims 22 and 25. In addition, we are not
persuaded by Appellants additional arguments for the reasons discussed
below.
First, Appellants argue:
A person of ordinary skill in the art seeking methods to
prophylactically decrease development of allergic asthma
would be discouraged from employing the IR-LPS of Previte in
the protocol of Cochran, as Previte teaches a single relative
high dose to adult rats which results in an unacceptably high
death rate among the subjects.
(App. Br. 12-13.) We are not persuaded.
We note initially that Cochran discloses administering LPS to
“developing mice” (Cochran 267: Abstract). According to Appellants,
“Previte teaches only administration by injection of IR-LPS to adult
mammals to test for a decrease in toxicity, reporting death of nearly a third
of the subjects 6 days post-administration (see, e.g., Fig. 3)” (App. Br. 11).
However, in Figure 3, Previte discloses the death of subjects after a 1 day or
6 day challenge with Salmonella typhimurium (Previte 1611). Thus,
Appellants have not identified where Previte reports the death of nearly a
third of the subjects 6 days after IR-LPS administration. In any event,
Previte discloses that irradiation of LPS provides an “almost complete
elimination of lethality (Fig. 1) with only a slight decrease in antigenicity
(Fig. 3) and retention of pyrogenicity (Fig. 2)” (Previte 1613). Thus, we do
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not agree with Appellants that one of ordinary skill in the art would have
been discouraged from employing the less toxic IR-LPS in the protocol of
Cochran.
Appellants also argue that “the application of Baldridge for the
limitation of weekly administration of IR-LPS amounts to nothing more than
improper hindsight reasoning” (App. Br. 14). We note initially that claim 22
does not require weekly administration. However, even with regard to
claim 25, we are not persuaded.
As noted by Appellants, Baldridge relates to the use of MPL, a
derivative of LPS, as a vaccine adjuvant (Baldridge 2416-2417; App.
Br. 13). However, Baldridge does disclose giving the vaccines “at 1-4 week
intervals” (Baldridge 2417). In addition, we agree with the Examiner that
the “dosing schedule is an art-recognized results-effective variable which is
well within the purview of those of ordinary skill in the art at the time the
invention was made” (Ans. 19). Thus, we conclude that the Examiner has
set forth a prima facie case that weekly administration would have been
obvious, which Appellants have not adequately rebutted.
In addition, Appellants argue that the March 2009 Declaration6
“demonstrates unexpected results,” which rebut any prima facie case of
obviousness (App. Br. 18-20). We are not persuaded.
The Declaration demonstrates that there is a reduction in neutrophils
and an increase in TNFα and IL-5 using IR-LPS spray compared to both
water (controls) and LPS (Dec. ¶¶ 5-6). The Declaration concludes that “the
prolonged pre-treatment of the environment of infant mice with IR-LPS acts

6 Declaration of Dr. Sándor Sipka, submitted on March 2, 2009.
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to prevent the intensity of ragweed specific allergic reaction differentially
when compared to native LPS” (id. at ¶ 6). However, the Examiner
questions the significance of these differences, specifically whether these
differences are indicative of a decrease in the development of allergic
asthma (Ans. 22). We note that the Declaration refers to the “surprisingly
superior effect of IR-LPS over native LPS in protecting against the
development of a hyper-immune response to an allergen” (Dec. ¶ 7).
However, we agree with the Examiner that Appellants have not adequately
explained how this conclusory statement is supported by the evidence of
record.
The evidence of record supports the Examiner’s conclusion that
claims 22 and 25 would have been obvious. We therefore affirm the
obviousness rejection of claims 22 and 25. Claims 23 and 24 have not been
argued separately and therefore fall with claim 22. 37 C.F.R.
§ 41.37(c)(1)(vii).
II
The Examiner relies on Khan for teaching:
A process for decreasing development of allergic asthma (OVA
induced asthma) comprising exposing an infant, neonatal or
immature mammal maturing in an overly sterile environment
shortly after birth (3 week old laboratory mice) to
lipopolysaccharide derived from extracted bacterial endotoxin
(LPS) by administering an aerosol spray composition of the
mammal to a living environment/space (saline and air during
intratracheal aspiration) during maturation of the mammal (at
3 weeks) . . . .
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(Ans. 8.) In particular, the Examiner finds that Khan “teaches that ‘recent
evidence has suggested that post-natal exposure to endotoxin may protect
against the development of allergen sensitization and asthma’” (id.).
The Examiner relies on Previte and Baldridge as discussed above (id.
at 10).
Analysis
Appellants argue “that Khan explicitly teaches away from the use of
LPS in reducing subsequent allergic responses, . . . since Khan states that
‘airway exposure to LPS produces transient AHR (airway hyper-
responsiveness) and inflammation in developing mice and does not appear to
influence functional and immune responses induced by subsequent allergen
sensitization’” (App. Br. 30). We agree. We therefore reverse the
obviousness rejection over Khan in view of Previte and Baldridge.
SUMMARY
We affirm the obviousness rejection of claims 22-25 over Cochran in
view of Previte and Baldridge. However, we reverse the obviousness
rejection of claim 1-3, 5, 10, 13, 17, and 18 over Kahn in view of Previte and
Baldridge and the obviousness rejection of claims 1-3, 5, 10, 13, 17, 18, and
22-25 over Kahn in view of Previte and Baldridge.
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. § 1.136(a).

AFFIRMED-IN-PART
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