Blanchard, Carine et al.

Patent Trials and Appeals Board

Sep 13, 2019

14429147 - (D) (P.T.A.B. Sep. 13, 2019)

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.
14/429,147 03/18/2015 Carine Blanchard 3712036-02395 3259
29157 7590 09/13/2019
K&L Gates LLP-Chicago
P.O. Box 1135
Chicago, IL 60690
EXAMINER
THOMAS, TIMOTHY P
ART UNIT PAPER NUMBER
1611
NOTIFICATION DATE DELIVERY MODE
09/13/2019 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):
USpatentmail@klgates.com
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte CARINE BLANCHARD and SEBASTIEN HOLVOET
__________

Appeal 2019-003848
Application 14/429,147
Technology Center 1600
__________

Before DEMETRA J. MILLS, FRANCISCO C. PRATS, and
DAVID COTTA, Administrative Patent Judges.

MILLS, Administrative Patent Judge.

DECISION ON APPEAL

This is an appeal under 35 U.S.C. § 134(a). The Examiner has rejected
the claims for obviousness. We have jurisdiction under 35 U.S.C. § 6(b).
We reverse.
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STATEMENT OF CASE

The following claim 1 is representative.
1. A method for treatment of eosinophilic esophagitis in
an individual in need thereof, the method comprising
administering to the individual a composition comprising plant
phenols that are plant extracts from thyme, pomegranate, and
green coffee.

Cited References
Straumann et al., “Pediatric and adult eosinophilic esophagitis:
similarities and differences,” 67 Allergy 477–490 (2012).

Singh et al., “Dietary polyphenols in the prevention and treatment
of allergic diseases,” Clinical & Experimental Allergy 1–14 (2011).

Farah et al., “Chlorogenic Acids from Green Coffee Extract are
Highly Bioavailable in Humans,1,2 ” 138 J. Nutr. 2309–2315
(2008).

Rogerio et al., “The activity of medicinal plants and secondary
metabolites on eosinophilic inflammation,” 62 Pharmacological
Research 298–307 (2010).

Sanbongi et al., “Rosmarinic acid in perilla extract inhibits allergic
inflammation induced by mite allergen, in a mouse model,” 34 Clin.
Exp. Allergy 971–977 (2004).

Grounds of Rejection

Claims 1, 6, 9–11, 15–17, and 20 are rejected under pre-AIA 35 U.S.C.
§ 103(a) as being unpatentable over Straumann in view of Singh,
Farah, Rogerio, and Sanbongi.

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FINDINGS OF FACT
The Examiner’s findings of fact are set forth in the Answer at pages
3–22. The following facts are highlighted.
1. Straumann teaches that evidence has accumulated that
eosinophilic esophagitis (EoE) represents a T-helper (Th)2-type
inflammatory disease; remodeling of the esophagus is a
hallmark of EoE, leading to esophageal dysfunction and bolus
impaction; there is a significant allergic bias in the EoE
population, with the majority of patients having concurrent
allergic rhinitis, asthma, eczema and/or a history of atopy; in
children, EoE seems to be primarily a food antigen-driven
disease (abstract). Final Act. 5.

2. Straumann teaches that eosinophils are not normally found in
the esophageal epithelium, and the quantity of intraepithelial
eosinophils is a crucial component in the diagnosis of EoE;
over time, in children, intraepithelial eosinophils may increase
(p. 479, 3rd paragraph). Final Act. 5.

3. Straumann teaches that Drug therapies include systemic and
topical corticosteroids, effective in evoking histologic and
symptomatic EoE remission (p. 484–485) and biologic agents,
including mepolizumab, a humanized anti-lL-5 antibody and
monoclonal anti-lL-5 antibodies used in adult and pediatric
clinical trials, and elimination diets, which eliminate
foodsensitizers (p. 185). Final Act. 5.

4. Straumann does not specifically discuss plant phenols
administered, or any of the plant extracts of claim 5.

5. Straumann establishes eosinophilic esophagitis (EoE) is a T-
helper (Th)2-type inflammatory disease, with a majority of
children having food antigen-driven disease; characteristic of
the disease is the presence of eosinophils in the inflamed
esophagus. Final Act. 5-6.
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6. Singh teaches allergic disorders encompass skin, food and
respiratory allergies. Sensitization to a normally harmless
allergen results in the immune system being biased to a
predominant T-helper type 2 response. Abstract. Re-exposure
to the same allergen leads to a robust secretion of allergy-
related mediators that eventually triggers symptoms. Our
understanding of these disorders has enabled the search of
therapeutic approaches that can either modulate the
sensitization process or impact on allergic mediators, thus
helping manage allergic symptoms. Abstract; Final Act. 6.

8. Singh teaches that polyphenols are one such class of
compounds that are found in foods and plant sources and have
been investigated for their anti-allergic effect in different
disease models and in human clinical trials. Their anti-
inflammatory profile is known to impact on the recruitment of
immune cells to the skin and in preventing the development of
secondary infections following disruption of the skin barrier.
The interaction of polyphenols with proteins can modulate the
process of allergic sensitization and their direct effect on
allergic effector cells such as mast cells inhibit mediator
release, resulting in the alleviation of symptoms. In addition,
their endogenous antioxidant ability limits the extent of cellular
injury from free radicals during the allergic insult. Final Act. 6.

9. Singh teaches that polyphenols hold promise as anti-allergy
agents capable of influencing multiple biological pathways and
immune cell functions in the allergic immune response and
deserve further investigation (Summary; p. 2). Dietary
polyphenols are a class of bioactive compounds that are found
in abundance in plant (tea, cocoa, coffee, etc.) and fruit (apple,
grapes, pomegranate, etc.) sources and have been studied
extensively in numerous disease models. The safety profile of
dietary polyphenols and their presence in the daily diet suggest
that these compounds should be evaluated further as antiallergy
agents (pp. 1-2, bridging paragraph). Final Act. 7.

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10. Singh, Figure 2, displays the mechanism of action of
polyphenols in allergic disorders: Polyphenols can impact the
development of allergic immune responses at two critical
stages: allergic sensitization and during re-exposure to the
allergen. Polyphenols can form insoluble complexes with
allergenic proteins and render them hypoallergenic. This leads
to inefficient antigen presentation by specialized cells such as
dendritic cells (DCs). Polyphenols can also directly modulate
DC maturation and function. During re-exposure, polyphenols
can inhibit T cell proliferation and cytokine production and also
impact on antibody production via B cells. Polyphenols such as
quercetin can inhibit mediator release from allergic effector
cells such as mast cells (p. 5). Final Act. 7.

11. Singh teaches polyphenols include ellagic acid (Figure 1),
luteolin, found in thyme (Table 1), chlorogenic acid, a phenolic
acid found in coffee (Table 1), caffeic acid (Table 3), luteolin,
rosmarinic acid and rutin, found in thyme (Table 3);
chlorogenic and caffeic acid, from coffee (Table 4).
Chlorogenic and caffeic acid inhibited pulmonary eosinophilia
and reactive oxygen species; chlorogenic acid decreased
specific IgE and Th2 cytokines (Table 4). The section bridging
pp. 8-9 indicates polyphenols inhibit airway inflammation and
tissue eosinophilia, inhibiting Th-2-driven allergic
inflammation in animal models of allergic airway disease. Final
Act. 8.

12. Singh teaches routes of administration of polyphenols include
oral (p. 10, 7th paragraph); oral administration of apple extract
was used in a clinical study (p. 10, 2nd paragraph). Use as
dietary interventions (construed as administration of plant
extracts as part of oral nutritional supplements) (p. 10, 8th
paragraph); it is noted that plant extracts, such as those
administered orally in a clinical trial at p. 10, 2nd paragraph are
also construed as oral nutritional supplements. Final Act. 8.

13. Singh establishes that a series of polyphenols function to treat
allergic disorders, including those that involve activating a T-
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helper type 2 response; some polyphenols, including
chlorogenic acid and caffeic acid, in coffee, inhibit eosinophilia
and reactive oxygen species, and chlorogenic acid decreased
specific IgE and Th2 cytokines. Final Act. 8.

14. Farah teaches chlorogenic acids (CGA) are produced from
green coffee, which is a major source of CGA found in nature
(abstract); the major CGA in green coffee include 3-
caffeoylquinic acid (3-CQA; p. 2309, 2nd paragraph). As
shown in Table 1 (p. 2310) the contents of green coffee extract
includes 3-CQA, in the second highest amount. 15. Farah
establishes that chlorogenic acid, taught to be in coffee by
Singh, may be obtained from green coffee extract as a major
plant source of this polyphenol compound. Final Act. 8.

15. Rogerio teaches eosinophils are leukocytes that are present in
several body compartments and in the blood at relatively low
numbers under normal conditions. However, an increase in the
number of eosinophils, in the blood or in the tissues, is
observed in allergic or parasitic disorders. Plant-derived
secondary metabolites are the basis for many drugs currently
used to treat pathologic conditions, including eosinophilic
diseases. Final Act. 10.

16. Rogerio discloses several studies have demonstrated that plant
extracts and secondary metabolites can reduce eosinophilia and
eosinophil recruitment in different experimental animal models.
In this review, we summarize these studies and describe the
anti-eosinophilic activity of various plant extracts, such as
Ginkgo biloba, Allium cepa, and Lafoensia pacari, as well as
those of secondary metabolites (compounds isolated from plant
extracts), such as quercetin and ellagic acid. In addition,
Rogerio highlights the medical potential of these plant-derived
compounds for treating eosinophil-mediated inflammation,
such as asthma and allergy (abstract). Initial exposure of the
immune system to allergens or parasitic antigens leads to the
activation of a subset of T cells, known as T helper 2 (TH2)
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cells, which orchestrate the immune response to these
exogenous antigens by secreting cytokines, including IL-4, IL-5
and IL-13 (p. 299, 2nd paragraph). Initial exposure of the
immune system to allergens or parasitic antigens leads to the
activation of a subset of T cells, known as T helper 2 (TH2)
cells, which orchestrate the immune response to these
exogenous antigens by secreting cytokines, including IL-4, IL-5
and IL-13 (p. 299, 4th paragraph). Although the drugs
described above have potent anti-inflammatory activity
(individually or combined), they also have adverse side effects
that severely limit their long-term use (p. 299, last paragraph).
Among the secondary metabolites with anti-eosinophil activity,
Table 3 names ellagic acid, as a polyphenol. Final Act. 11.

17. Rogerio discusses studies using extracts of L pacari, including
in an asthma model induced by T. canis infection, which
decreased the number of eosinophils recruited to several tissues
and compartments; in an OVA-induced asthma model, where
the extract was effective in decreasing eosinophil recruitment
and the production of IL-4, IL-5 and IL-13; in a model of
peritonitis induced in mice by exposure to H. capsulatum yeast
wall, the assay permitted isolation and chemical characteri-
zation of the compound ellagic acid, a polyphenol, as the major
active component in the L pacari extract, the first study to
demonstrate the ability of ellagic acid to inhibit eosinophil
recruitment; it was shown that ellagic acid, at 1 and 10 mg/kg,
p.a. (Applicant elected oral administration of a composition
comprising plant phenols), induced reduction in the numbers of
eosinophils and lung parenchyma in the asthma model; and
ellagic acid was effective in decreasing the concentrations of
IL-4, IL-5 and IL-13. Ellagic acid also demonstrates several
other biologic effects, including anti-oxidant, anti-cancer and
antiallergic activity. Concerning its toxicity, intake of
pomegranate juice (extract of pomegranate; construed as an oral
nutritional supplement) with an equivalent concentration of 121
mg/L of ellagic acid produced no toxic effect in humans over 3
years and conferred the benefits of reduced common carotid
intima-media thickness, blood pressure and low-density
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lipoprotein (LDL) oxidation (p. 202, 1st paragraph). Final Act.
12.
18. Rogerio establishes that ellagic acid, in the form of
pomegranate juice, is effective in decreasing eosinophil levels,
and reducing cytokines IL-4, IL-5 and IL-13 and has other
effects, including anti-oxidant, and anti-allergic activity. Final
Act. 12-13.

19. Sanbongi teaches perilla and its constituent rosmarinic acid
have been suggested to have anti-allergic activity (Summary;
Background). The purpose was to evaluate the effect of oral
administration of perilla leaf extract, which contains high
amount of rosmarinic acid, on a murine model of allergic
asthma induced by house dust mite allergen (Summary;
Objective). C3H/He mice were sensitized by intratracheal
administration of Dermatophagoides farinae (Der f). Final Act.
12–13.

20. Sanbongi teaches that mice were orally treated with rosmarinic
acid in perilla extract (PE) (1.5 mg/mouse/day) (Summary;
Methods). Der f challenge of sensitized mice elicited
pulmonary eosinophilic inflammation, accompanied by an
increase in lung expression of IL-4 and IL-5, and eotaxin.
Daily treatment with rosmarinic acid in PE significantly
prevented the increases in the numbers of eosinophils in
bronchoalveolar lavage fluids and also in those around murine
airways. Final Act. 13.

21. Sanbongi teaches Rosmarinic acid in PE treatment also
inhibited the enhanced protein expression of IL-4 and IL-5, and
eotaxin in the lungs of sensitized mice. Der f [Dermatopha-
goides farina] challenge also enhanced allergen-specific lgG1,
which were also inhibited by rosmarinic acid in PE (Summary;
Results). These results suggest that oral administration of
perilla-derived rosmarinic acid is an effective intervention for
allergic asthma, possibly through the amelioration of increases
in cytokines, hemokines, and allergen-specific antibody
(Summary; Conclusion). Final Act. 13.
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22. Sanbongi establishes that the polyphenol compound rosmarinic
acid is effective to reduce levels of eosinophils in a mouse
model of allergic asthma, and is accompanied by decreases in
IL-4, IL-5 and eotaxin levels, as well as IgG1 levels relative to
untreated challenge sensitized mice. Abstract; Final Act. 13.

PRINCIPLES OF LAW
In making our determination, we apply the preponderance of the
evidence standard. See, e.g., Ethicon, Inc. v. Quigg, 849 F.2d 1422, 1427
(Fed. Cir. 1988) (explaining the general evidentiary standard for proceedings
before the Office).

Obviousness Rejection
Claims 1, 6, 9–11, 15–17, and 20 are rejected under pre-AIA 35
U.S.C. 103(a) as being unpatentable over Straumann in view of Singh,
Farah, Rogerio, and Sanbongi.
The Examiner finds that Straumann teaches eosinophilic esophagitis
(EoE) is a T-helper (Th) 2-type inflammatory disease. Ans. 5; FF1. Singh
teaches allergic disorders and food allergies are a Th-2 inflammatory
condition. FF6. The Examiner finds that Singh discloses that polyphenols
are a
class of compounds that are found in foods and plant sources
and have been investigated for their anti-allergic effect in
different disease models and in human clinical trials. Their
anti-inflammatory profile is known to impact on the recruitment
of immune cells to the skin and in preventing the development
of secondary infections following disruption of the skin barrier.
The interaction of polyphenols with proteins can modulate the
process of allergic sensitization and their direct effect on
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allergic effector cells such as mast cells inhibit mediator
release, resulting in the alleviation of symptoms.

Final Act 6. Singh discloses that polyphenols modulate different phases of
the allergic response. P.2, col. 1, FF8. Singh discloses that, using animal
models of allergic airway disease, polyphenols have been shown to inhibit
Th-2-driven allergic inflammation. P. 8, col. 2, FF11. According to the
Examiner, “[p]olyphenols can form insoluble complexes with allergenic
proteins and render them hypoallergenic.” Final Act. 7. Singh specifically
mentions that the effect of many plant polyphenols on respiratory allergies
have been studied, including coffee polyphenols. P. 9, FF 11. Farah teaches
chlorogenic acids (CGA) are produced from green coffee. Final Act. 8.
The Examiner concludes that
the skilled artisan would have found it obvious at the time of
the instant invention to administer polyphenols taught by Singh,
including those found in extracts from green coffee taught by
Farah, i.e., containing chlorogenic acid, in treating the children
with eosinophilic esophagitis (EoE), a T-helper (Th)2-type
inflammatory disease, including the majority of children having
this food antigen-driven disease, taught by Straumann. The
motivation would have been the expectation that the inhibition
of eosinophilia and ROS [reactive oxygen species] by
chlorogenic acid and caffeic acid from coffee taught by Singh
would have been expected to provide a benefit in these
children, where increased levels are present, by reducing the
number of eosinophils and ROS in symptoms and pathology.
Additionally, the decreases in IgE and Th2 cytokines taught by
Singh from chlorogenic acid would have been expected to
reduce the severity of inflammation associated with
eosinophilic esophagitis. Additionally, reduction of the severity
of other allergic conditions present in the majority of these
children would also have motivated administration of green
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coffee extract to these children, including those in Applicant
elected age range from 6 to 18 years.

Final Act. 8–9.

Rogerio and Sanbongi teach well known polyphenols for the
treatment of eosinophilic inflammation and allergic inflammation, generally
(not specific to esophageal eosinophilic inflammation). Rogerio and
Sanbongi Abstracts. The Examiner concludes that
it would have been obvious to one of ordinary skill in the art at
the time of the instant invention, to combine … [the] elected
combination of an extract of green coffee, containing
chlorogenic acid, an extract of pomegranate, containing ellagic
acid, and an extract of thyme, containing rosmarinic acid (i.e.,
the combination of claims 1 & 15), and to orally administer this
combination composition as an oral nutritional supplement to
children with eosinophilic esophagitis, giving the methods of
the instant claims.

Final Act. 14.

Appellants contend that

eosinophilic esophagitis is an inflammatory condition of the
esophagus that can be triggered by an antigen. Symptoms
include functional abdominal pain, vomiting, difficulty to
thrive, swallowing difficulty, food impaction, and heartburn.
The disease was initially described in children, but occurs in
adults as well. See specification, page 1, second paragraph.
Appellant has surprisingly discovered that extracts of
thyme, pomegranate, green coffee, and mixtures thereof
decrease the presence of eosinophils. Administration of a
composition comprising these extracts is useful for the
treatment of eosinophilic esophagitis, which is characterized by
an increase of the number of eosinophils in certain tissues. See
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specification, page 6, first paragraph; and page 7, second
paragraph.

App. Br. 5.

Appellants argue that, “there is no reason or motivation for the skilled
artisan to combine or modify the teachings of Straumann with the teachings
of the other references to administer a composition comprising plant phenols
that are plant extracts from thyme, pomegranate, and green coffee to an
individual having eosinophilic esophagitis.” App. Br. 6. Appellants contend
that, “the skilled artisan would not have combined these [the cited]
references to arrive at the claimed invention with a reasonable expectation
of success.” App. Br. 13.

ANALYSIS
Appellants’ have made the following elections in the application:
(i-c) each plant extract containing a plant polyphenol from claim 5
(i.e., a mixture of extracts from thyme, pomegranate and green
coffee);
(ii) oral administration from claim 6;
(iii-b) an oral nutritional supplement from claim 11; and
(iv-b) an older child between the ages of 6–18 years from claim 10.

When the examiner has required the applicant to elect single chemical
species for examination, the issue on appeal is the patentability of the single
elected species. Accordingly, we limit our discussion to that single issue
and take no position respecting the patentability of the broader generic
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claims, including the remaining, non-elected species. See Ex parte Ohsaka,
2 USPQ2d 1461 (BPAI 1987).
To support patentability, and in response to the Examiner’s prima
facie case, the Appellants rely on two Declarations of Carine Blanchard
dated May 24, 2017 (Dec I), and January 29, 2018 (Dec II).
Appellants contend that, “the skilled artisan would not have combined
these [the cited] references to arrive at the claimed invention with a
reasonable expectation of success.” App. Br. 13. Appellants argue that,
Declaration I and Declaration II and the experimental
data therein (e.g., the data demonstrating that apple extract did
not reduce eosinophilia in the esophagus and lungs), establish
that contrary to the allegation by the Examiner, the skilled
artisan would not have extrapolated the results disclosed by the
cited references to eosinophilic esophagitis[,] and moreover
would not have had a reasonable expectation of success even if
such extrapolation was attempted.

App. Br. 13.
Appellants argue that the Declaration evidence shows that
polyphenols which act on the lung do not predictably act in the esophagus to
reduce eosinophil levels. Reply Br. 3. In particular, Appellants argue that
there is no evidence in the record that the polyphenols
having effects on lung inflammation as disclosed in the cited
references would have the same or similar effects on
eosinophilic esophagitis.
Further, as discussed in Declaration II, Appellant found
that some [polyphenol] ingredients were potent on EoE, but
were not able to significantly decrease clinical skin score of
atopic dermatitis or lung inflammation. Not all polyphenols
are equivalent at decreasing allergic features, and the model
used or the type of allergen may influence the potency of the
polyphenols. See Declaration 11, paragraphs 3-26.
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Reply Br. 3. Polyphenol treatment effectiveness of various tissues are
shown in the tables below, and are reproduced from Declaration I ¶ 6.

The above Tables from Declaration I ¶ 6 show that some polyphenols
tested were not effective in the lungs but were effective in the esophagus,
and that whether a specific polyphenol is effective in the esophagus or other
tissues is not predictable. See also Declaration II ¶¶ 15, 18, 26.
This table shows that thyme, pomegranate and green coffee polyphenols
were effective in the esophagus to reduce eosinophil counts but were not
effective in the lungs. Thus, the cited references dealing with polyphenols
effective for the treatment of pulmonary eosinophilia and asthma are not
reliable predictors of efficacy in the esophagus.
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We produce the Table from paragraph 15 of Declaration II. The main
objective of this study was to confirm that Thyme extracts given in
management reduce the TEWL (Transepidermal water loss) scores
(compared to the positive control group) during the first 3 days after patch 2
(thyme) removal. This reducing effect was indeed observed, especially at
day 3.

In response, the Examiner argues that
the rejection is based on the documentation that each of
the plant extracts from thyme, pomegranate and green coffee
reduce eosinophils and inflammatory cytokines, including IL-4,
IL-5 and IL-13, and have anti-inflammatory and anti-allergy
effects in an allergic asthma or other allergy animal model.
Even though the allergic models differ from EoE, based on the
teachings of Straumann that EoE is believed to be triggered by
aero- and food allergens, the allergic disorders scheme of Singh
Figure 2, is directly relevant for applying polyphenols with
desirable characteristics to treating EoE.

Ans. 17. The Examiner argues that, “While there are differences in effects
of eosinophils in lungs (thyme and pomegranate having no effect, but green
coffee having decrease), it is not clear how this is being argued to overcome
obviousness.” Ans. 26. What is missing from the Examiner’s analysis is an
understanding that differences in polyphenol response in the lungs versus the
esophagus have a bearing on the finding of an expectation of success and
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ultimately on the obviousness determination. In fact, Dr. Blanchard
concluded in Declaration II, ¶ 26 that,

While the results with apple extract is surprising considering the
previous published data, this emphasizes that all polyphenols may not
be equivalent at decreasing allergic features and that the model used
(IgE mediated, IgG mediated or T cell mediated) or the type of
allergen may influence the potency of the polyphenols. An extract
containing a variety of polyphenols, such as cocoa containing both
epicatechin and procyanidins may thus cover a larger spectrum of
allergic diseases.

The question of obviousness is resolved on the basis of underlying
factual determinations including: (1) the scope and content of the prior art;
(2) the level of ordinary skill in the art; (3) the differences between the
claimed invention and the prior art; and (4) secondary considerations of
nonobviousness, if any. Graham v. John Deere Co., 383 U.S. 1, 17 (1966).
“When prima facie obviousness is established and evidence is submitted in
rebuttal, the decision-maker must start over.” In re Rinehart, 531 F.2d 1048,
1052 (CCPA 1976); In re Hedges, 783 F.2d 1038, 1039 (Fed. Cir. 1986) (“If
a prima facie case is made in the first instance, and if the applicant comes
forward with reasonable rebuttal, whether buttressed by experiment, prior art
references, or argument, the entire merits of the matter are to be
reweighed”).
On weighing the evidence presented in the Blanchard Declarations,
we find that Appellants have established a lack of expectation of success on
the part of one of ordinary skill in the art. The evidence presented in
Declarations I and II shows that the polyphenols used in the prior art to treat
allergies and pulmonary eosinophilia do not produce predictable results in
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different body tissues and therefore the cited references do not provide an
expectation of success for the treatment of esophageal eosinophilia.
KSR Int’l v. Teleflex Inc., 550 U.S. 398, 418–19 (2007) held that,
“[t]he combination of familiar elements according to known methods is
likely to be obvious when it does no more than yield predictable results.”
Id. at 416 emphasis added. Singh, p. 2, discloses that different polyphenols
modulate different phases of the allergic response. Thus, consistent with
Appellants’ arguments and Declaration evidence, it appears that different
polyphenols act upon different tissues in different ways. The only cited
reference dealing with eosinophilic esophagitis, Straumann, did not mention
polyphenols, let alone the combination of three polyphenols claimed. The
facts of the present case do not establish an expectation of success or yield
predictable results, and thus do not support a finding of obviousness.
The obviousness rejection is reversed.

CONCLUSION OF LAW
The Examiner’s obviousness rejection is reversed with respect to the
elected species.

REVERSED