Benyacoub, Jalil et al.

Patent Trials and Appeals Board

Oct 2, 2019

15468961 - (D) (P.T.A.B. Oct. 2, 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.
15/468,961 03/24/2017 Jalil Benyacoub 3712036-02865 7905
29157 7590 10/02/2019
K&L Gates LLP-Chicago
P.O. Box 1135
Chicago, IL 60690
EXAMINER
HINES, JANA A
ART UNIT PAPER NUMBER
1645
NOTIFICATION DATE DELIVERY MODE
10/02/2019 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 JALIL BENYACOUB, BLAISE CORTHESY,
STEPHANIE BLUM-SPERISEN, and LAURENT FAVRE 1
____________

Appeal 2019-003679
Application 15/468,961
Technology Center 1600
____________

Before JEFFREY N. FREDMAN, DEBORAH KATZ, and JOHN G. NEW,
Administrative Patent Judges.

NEW, Administrative Patent Judge.

DECISION ON APPEAL

1 We use the term “Appellant” to refer to “applicant” as defined in 37 C.F.R.
§ 1.42. Appellant identifies the Real Party in Interest as Nestec S.A. App.
Br. 2.

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SUMMARY
Appellant files this appeal under 35 U.S.C. § 134(a) from the
Examiner’s Final Rejection of claims 1–17 as unpatentable under 35 U.S.C.
§ 112 (pre-AIA), first paragraph, for failing to comply with the enablement
requirement.
We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.

NATURE OF THE CLAIMED INVENTION
Appellant’s invention is directed to a method of treating non-viral
infections by administering a combination of probiotics and secretory IgA
(“SIgA”). Spec. ¶¶ 2, 38.

REPRESENTATIVE CLAIM
Claim 1 is representative of the claims on appeal and recites:
1. A method for treating non-viral infections, the method
comprising the step of:

administering to a subject in need thereof a
therap[e]utically-effective amount of a composition comprising
SIgA and probiotic microorganisms,

wherein the SIgA and the probiotic microorganisms are
present in the form of a complex with each other, and

the SIgA and the probiotic micro-organisms are present in
the composition in a stoichiometric ratio of at least 100:1.

App. Br. 10.
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ISSUES AND ANALYSIS
We agree with, and expressly adopt, the Examiner’s findings,
reasoning, and conclusion that the claims fail to comply with the enablement
requirement. We address the arguments raised by Appellant below.

Issue
Appellant argues that the examples of the Specification provide
enablement for the presently claimed method. App. Br. 6.

Analysis
The Examiner determines that “[t]he specification does not enable any
person skilled in the art to which it pertains, or with which it is most nearly
connected, to make and/or use the inventions commensurate in scope with
these claims.” Ans. 3. In making the determination, the Examiner addresses
the factors set forth in In re Wands, 858 F.2d 731, 737 (Fed. Cir. 1988). Id.
at 4. The Examiner finds the scope of the claims encompasses “treating any
and all non-viral infections such as bacterial, parasites, fungi, prion and
protozoan infections, by administering to any kind[] of subject, … a
therapeutically effective amount of a composition comprising SIgA and
probiotic microorganisms.” Id. at 5. The Examiner finds that the “art is
highly unpredictable.” Id. The Examiner finds that the “instant
specification fails to provide any experiments that show that a method for
treating any and all non-viral infections for individuals at risk for infection
by various species of non-viral microorganisms which would be effective in
protecting a human or other animal against any type of non-viral infection.”
Id.
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In considering the in vitro tests disclosed by the Specification, the
Examiner finds Appellant has “failed to demonstrate a reasonable correlation
to the treatment of any non-viral infection.” Ans. 6. The Examiner finds
that “[t]here is no evidence that the examples within the specification are
predictive of a method of treating any non-viral infection. The in vitro
experiments do not correlate to treatment of any specific non-viral disease.”
Id. at 9.
With respect to the Declaration of Jalil Benyacoub, Ph.D., filed June
4, 2018 (the “Benyacoub Decl.”), the Examiner finds that the “Declarant
does not correlate the in vitro experiments to any specific condition.” Ans.
16. The Examiner finds “Declarant has not provided [] extrapolative
evidence to correlate the in vitro experiments to any specific non-viral
infection.” Id. More specifically, the Examiner finds evidence that the
probiotic-SIgA complex: 1) induces activation of transcription factor nuclear
factor kappa-light-chain-enhancer of activated B cells (“NF-κB”), 2) induces
production of thymic stromal lymphopoeitin (“TSLP”), and 3) increases
expression of polymeric Ig receptor (“pIgR”), is not correlated to the
treatment of any non-viral infection. See id. at 16–20.
Appellant argues that “the examples in the specification provide
experimental evidence that SIgA and probiotics are responsible for
increasing the immune response involved in the treatment and reduction of
all kind of non-viral infections.” Reply Br. 2. Appellant argues that the
Benyacoub Declaration and accompanying references disclose “that the
experimental examples in the specification ‘correlate’ with the presently
claimed invention and therefore, constitute ‘working examples’ that provide
enablement for the claimed invention.” Id. at 3 (emphasis omitted).
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The Benyacoub Declaration discloses that the probiotic-SIgA
complex induces activation of transcription factor NF-κB. Benyacoub Decl.
2, citing Spec. Example 3; Mathias A., et al., Potentiation of Polarized
Intestinal Caco-2 Cell Responsiveness to Probiotics Complexed with
Secretory IgA, 285 J. BIOL. CHEM. 33906–33913 (2010) (“Mathias 2010”).
“Broad activation [of NF-κB] will predispose the immune system to be more
reactive and efficient to antigenic challenges which is key to support
defences [sic] against multiple infections of various []etiologies.” Reply Br.
3. The Benyacoub Declaration discloses that the probiotic-SIgA complex
promotes the production of TSLP. Id., citing Mathias 2010. “This cytokine
is instrumental in activation of dentritic cells as well as B cells, two major
immune components for the defences [sic] against pathogens irrespective of
pathogen[] origin, could it be bacteria or parasites or helminths. Id. The
Benyacoub Declaration discloses that the probiotic-SIgA complex increases
expression of pIgR. Id. at 2–3, citing Spec. Fig. 7. “pIgR is essential for the
secretion of the SIgA produced by the host and is thus a key factor[] in
protection of the host against infections, including of non-viral []etiology.”
Id. The Benyacoub Declaration discloses the probiotic-SIgA complex can
lead to enhanced production of mucosal IgA in a host. Id. at 3, citing
Mathias A., et al., Role of secretory IgA in the mucosal sensing of
commensal bacteria, 5 GUT MICROBES 685–695 (2014) (“Mathias 2014”).
“The overall role of SIgA in protecting the host against pathogens is well
documented and this includes bacteria, parasites or helminths.” Id.
Appellant argues that “the skilled artisan, given the level of knowledge and
skill in the art, would be able to correlate the experimental examples in the
application with the claimed methods of treating non-viral infections and
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therefore, be able to practice the claimed invention without undue
experimentation.” Reply Br. 4.
We are not persuaded by Appellant’s arguments. “Whether undue
experimentation is needed is not a single, simple factual determination, but
rather is a conclusion reached by weighing many factual considerations.”
Wands, 858 F.2d at 737. Appellant does not dispute the Examiner’s findings
that the claims have a very broad scope, i.e., treating any non-viral
infection.2 The references cited by Appellant confirm the Examiner’s

2 We note that the extreme breadth of “non-viral infection” as disclosed in
the Specification includes a very large and diverse set of diseases:

Typical bacterial infectious diseases that can be treated or
prevented by the present invention include salmonellosis,
shigellosis, typhoid fever, bacterial meningitis, anthrax,
botulism, brucellosis, campylobacteriosis, cat scratch disease,
cholera, diphtheria, epidemic typhus, gonorrhea, impetigo,
legionellosis, leprosy (Hansen's Disease), leptospirosis,
listeriosis, lyme disease, melioidosis, rheumatic fever, MRSA
infection, nocardiosis, pertussis (whooping cough), plague,
pneumococcal pneumonia, psittacosis, Q fever, Rocky Mountain
Spotted Fever (RMSF), scarlet fever, syphilis, tetanus, trachoma,
tuberculosis, tularaemia, typhus, and/or urinary tract infections.

Typical parasitic infectious diseases that can be treated or
prevented by the present invention include african
trypanosomiasis, amebiasis, ascariasis, babesiosis, Chagas
disease, clonorchiasis, cryptosporidiosis, cysticercosis,
diphyllobothriasis, dracunculiasis, echinococcosis, enterobiasis,
fascioliasis, fasciolopsiasis, filariasis, free-living amebic
infection, giardiasis, gnathostomiasis, hymenolepiasis,
isosporiasis, kala-azar, leishmaniasis, malaria, metagonimiasis,
myias1s, onchocerciasis, pediculosis, pmworm infection,
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finding of a high level of unpredictability in the art. See In re Goodman, 11
F.3d 1046, 1051 (Fed. Cir. 2005) (“the references cited by [Appellant] to
show enablement support the Board’s position that great uncertainties
encumbered [the technology]”). For example, Mathias 2010 discloses that
“[t]he role of probiotic and commensal bacteria in the physiology of the
gastrointestinal tract is incompletely understood, … [and] the mechanisms
underlying the beneficial effects of probiotics … are still in need of
investigation.” Mathias 2010, 33912. Mathias 2014 discloses that “[t]he
importance of commensal bacteria in the maintenance of the integrity of
intestinal epithelial cell (IEC) barrier and the control of the underlying
immune mechanisms ensuring homeostasis is a fundamental process, whose
multiple and complex features are not yet fully understood.” Mathias 2014,
689.
Given the broad reach of the claims in an unpredictable field,
Appellant relies on the in vitro examples of the Specification as enabling the
claims. “An in vitro or in vivo animal model example in the specification, in
effect, constitutes a ‘working example’ if that example ‘correlates’ with a

scabies, schistosomiasis, taeniasis, toxocariasis, toxoplasmosis,
trichinellosis, trichinosis, trichuriasis, trichomoniasis, and/or
trypanosomiasis.

Typical fungal infectious diseases that can be treated or
prevented by the present invention include aspergillosis,
blastomycosis, candidiasis, coccidioidomycosis, cryptococcosis,
histoplasmosis, and/or tinea pedis.

(Spec. ¶¶ 47–49).

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disclosed or claimed method invention. Edwards Lifesciences AG v.
CoreValve, Inc., 699 F.3d 1305, 1310 (Fed. Cir. 2012). Only a reasonable
correlation is necessary “where the disclosure of pharmacological activity is
reasonable based on the probative evidence.” Cross v. Iizuka, 753 F.2d
1040, 1050 (Fed. Cir. 1985). As discussed in detail below, we conclude that
the in vitro examples and references cited in the Benyacoub Declaration are
not reasonably correlated to the pharmacological activity of treating any
non-viral infection.
Example 1 discloses that SIgA improves probiotic binding capacity to
Caco-2 epithelial cells. Spec. ¶¶ 78–84. Example 2 discloses incubating
epithelial cells with probiotic-SIgA complex increases transepithelial
electrical resistance (“TER”). Spec. ¶¶ 85–89. Appellant does not explain
any correlation between either of Examples 1 and 2 and treating non-viral
infections.
Example 3 discloses incubating epithelial cells with probiotic-SIgA
complex “reduced NF-κB activation” as compared to exposure to the
probiotic (Lactobacillus rhamnosus (“LPR”)) alone, or to pathogenic
bacteria. Spec. ¶¶ 90–95. According to Mathias 2010, “[t]his indicates that
exposure of epithelial cells to certain probiotic microorganisms such as LPR
… maintains a low, if not basal, degree of NF-κB activation that may be
instrumental for the maintenance of homeostasis.” Mathias 2010, 33912.
Moreover, “induction of NF-κB after exposure to ... SIgA-probiotic
complexes did not lead to the production by Caco-2 cells of chemokines
involved in the recruitment of pro-inflammatory cells.” Id. We do not find
this in vitro example to be probative evidence of treating a non-viral
infection.
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Example 4 discloses pre-treating epithelial cells with the probiotic-
SIgA complex “reduced the infection of polarized Caco-2 cell monolayer by
S. flexneri.” Spec. ¶¶ 96–100. This example arguably discloses the
pharmacological activity of one probiotic complex with one bacterial
infection. However, Appellant has not established a correlation between this
specific example and the breadth of the claims, in particular, establishing a
“therapeutically-effective amount” for a subject for treating any non-viral
infection. Cf. Cross, 753 F3d. at 1052 (“This is not a case such as In re
Gardner, 427 F.2d 786, 166 USPQ 138 (1970), where the CCPA held that
the applicant’s disclosure was nonenabling because inventive skill and
undue experimentation would be required to discover appropriate dosages
for humans, i.e., a therapeutic use.”)
Example 5 discloses incubating epithelial cells with the probiotic-
SIgA complex increased pIgR synthesis. Spec. ¶¶ 101–107. According to
Mathias 2010, “[t]hese results indicate that the interaction between a
probiotic-SIgA complex and epithelial Caco-2 cells prompts these latter to
synthesize more pIgR involved in mucosal defense.” Mathias 2010, 33911.
We do not find this in vitro example to be probative evidence of treating a
non-viral infection.
We further consider examples of the probiotic-SIgA complex
increasing production of TSLP and mucosal IgA as disclosed in the
Benyacoub Declaration. There is no teaching in the Mathias references for a
correlation between these mechanisms and treating a non-viral infection.
Like the other interactions between the probiotic-SIgA complex and the
immune system of the gastrointestinal tract, “[t]hese data provide partial
clues as to the still puzzling issue of how SIgA contributes to the complex
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mechanisms of actively regulating mucosal immune homeostasis, in
particular discrimination between noxious and resident microorganisms.”
Mathias 2014, 691.
Because Appellant has not shown a reasonable correlation between
the disclosed in vitro utility and an in vivo activity, we conclude that
Appellant’s disclosure is nonenabling for the full scope of the claimed
invention, as inventive skill and undue experimentation would be required to
discover appropriate methods for treating non-viral infection. See Cross,
753 F.2d at 1052. “Thus, at the end of the day, the specification, even read
in the light of the knowledge of those skilled in the art, does no more than
state a hypothesis and propose testing to determine the accuracy of that
hypothesis. That is not sufficient.” In re ’318 Patent Infringement Litig.,
583 F.3d 1317, 1327 (Fed. Cir. 2009). Accordingly, we sustain the
Examiner’s rejection.

CONCLUSION

The rejection of claims 1–17 as unpatentable under 35 U.S.C. §112,
first paragraph, is affirmed.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(1).

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AFFIRMED

Claims
Rejected
35 U.S.C. § Basis Affirmed Reversed
1–17 112, first paragraph Enablement 1–17
Overall
Outcome
1–17