Scott Dorfner

Patent Trials and Appeals Board

Dec 23, 2019

13162129 - (D) (P.T.A.B. Dec. 23, 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.
13/162,129 06/16/2011 Scott Dorfner D0099-3U1 6873
54380 7590 12/23/2019
FLASTER/GREENBERG P.C.
1810 Chapel Avenue West
Cherry Hill, NJ 08002
EXAMINER
AFREMOVA, VERA
ART UNIT PAPER NUMBER
1653
NOTIFICATION DATE DELIVERY MODE
12/23/2019 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):
robin.graham@flastergreenberg.com
thomas.durling@flastergreenberg.com
usp@flastergreenberg.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
________________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
________________

Ex parte SCOTT DORFNER1
________________

Appeal 2019-001443
Application 13/162,129
Technology Center 1600
________________

Before JEFFREY N. FREDMAN, JOHN G. NEW, and
JAMIE T. WISZ, Administrative Patent Judges.

NEW, Administrative Patent Judge.

DECISION ON APPEAL

1 We use the word “Appellant” to refer to the “applicant” as defined in
37 C.F.R. § 1.142. Appellant identifies Tecoppa Biopharma, LLC as the
real party-in-interest. App. Br. 4.
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SUMMARY
Appellant files this appeal under 35 U.S.C. § 134(a) from the
Examiner’s Final Rejection of claims 93–118. Specifically, claims 93–116
stand rejected as unpatentable under 35 U.S.C. § 112, first paragraph, for
lack of enablement.
Claims 93–118 stand rejected as unpatentable under 35 U.S.C.
§ 103(a) as being obvious over the combination of T. Arvola et al.
Prophylactic Lactobacillus GG Reduces Antibiotic-Associated Diarrhea in
Children with Respiratory Infections: A Randomized Study, 104(5)
PEDIATRICS 1–4 (1999) (“Arvola”), D.L. Witsell et al., Effect of
Lactobacillus acidophilus on Antibiotic-Associated Gastrointestinal
Morbidity: A Prospective Randomized Trial, 24(4) J. OTOLARYNGOL. 230–
233 (1995) (“Witsell”), Farmer (US 7,807,151 B2, October 5, 2010)
(“Farmer”), and Fitzpatrick et al. (US 2009/0252708 A1, October 8, 2009)
(“Fitzpatrick”).
We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.

NATURE OF THE CLAIMED INVENTION
Appellant’s claimed invention is directed to a method of treating a
patient with a formulation comprising: (1) a therapeutically effective amount
of at least one antibiotic; and (2) a therapeutically effective amount of at
least one probiotic material. Abstr.

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REPRESENTATIVE CLAIM
Claim 93 is representative of the claims on appeal and recites:
93. A method of treatment of a patient having a non-
gastrointestinal tract infection selected from bacterial sinusitis, a
sexually transmitted disease of bacterial origin, pharyngitis,
otitis, otitis media, bacterial bronchitis, bacterial pneumonia, a
urinary tract infection, and skin and skin structure infections,
cellulitis, abscesses, furuncles, impetigo, pyoderma, wound
infections, acne, nail infections, chronic bacterial prostatitis, and
pyelonephritis while simultaneously preventing a Clostridium
difficile infection of a gastrointestinal tract of the patient
comprising:

administering a formulation to the gastrointestinal tract of the
patient comprising at least one antibiotic in an amount sufficient
to be systemically therapeutically effective for the
nongastrointestinal tract infection of the patient and at least one
probiotic material, wherein the formulation is a dosage form for
delivery to the gastrointestinal tract and the antibiotic and the
probiotic material are in physical contact with one another in the
formulation whereby the nongastrointestinal tract infection is
treated and the patient is prevented from developing a
Clostridium difficile infection of the gastrointestinal tract.

App. Br. 23.

ISSUES AND ANALYSES
We agree with, and adopt, the Examiner’s findings, reasoning, and
conclusion that the claims on appeal are not enabled and are obvious over
the combined cited prior art. We address the arguments raised by Appellant
below.

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A. Rejection of claims 93–116 under 35 U.S.C. § 112, first paragraph
Issue
Appellant argues that the Examiner erred in concluding that
Appellant’s Specification does not reasonably enable treating all claimed
non-gastrointestinal disorders and/or infections. App. Br. 10; see also Final
Act. 2.

Analysis
The Examiner finds that the scope of the claims encompasses
prevention of Clostridium difficile infections for a long list of “non-
gastrointestinal tract” diseases (claim 93), or for a long list of pathogens
causing non-gastrointestinal tract infections that are also pathogens of
gastrointestinal tract (claim 105), for several long lists of various and nearly
all possible antibiotics (claims 95–99, 108–11) and for a large list
comprising generic bacterial species (claims 101, 113). Final Act. 2–3.
The Examiner finds that guidance disclosed by Appellant’s
Specification is generic with regard to specific combinations of probiotic
and antibiotic for specific patients under treatment. Final Act. 3. The
Examiner similarly finds that the guidance in the two working examples
disclosed by the Specification is limited to only two patients: (1) a patient
diagnosed with pneumonia treated with levofloxacin compounded together
with Lactobacillus acidophilus in a single capsule; and (2) a second patient
with a middle ear infection treated with a suspension comprising
amoxicillin, clavulonic acid and L. acidophilus. Id. The Examiner finds that
the Specification discloses that the condition of patients was resolved
without adverse gastrointestinal effects, but it is uncertain that the
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Specification discloses whether or not patients were at any risk of
developing of a C. difficile infection, because no bacteriological analysis for
potential presence of C. difficile was performed or considered. Id.
The Examiner finds that the prior art teaches the unpredictability of
probiotic administration, including treatments of seriously ill patients with
sepsis, pneumonia, etc. Final Act. 3 (citing, e.g., L.E. Morrow, Probiotics in
the Intensive Care Unit, 15(2) CURR. OPIN. CRIT. CARE 144–48 (2009)
(“Morrow”)). The Examiner finds that Morrow teaches that the success of a
probiotic agent in any one clinical setting does not guarantee a similar in
another. Id. (citing Morrow 147). Moreover, the Examiner finds that the
claimed generic genus of probiotic bacteria, including Lactobacillus and
Bifidobacteria, are sensitive to certain antibiotics including those that are
listed in the pending claims. Id. (citing, e.g., S. Delgado et al., Antibiotic
Susceptibility of Lactobacillus and Bifidobacterium Species from the Human
Gastrointestinal Tract, 50(4) CURR. MICRIBIOL. 202–07, Abstr. (2005)
(“Delgado”)).
The Examiner concludes that it would have required undue
experimentation to practice the invention as claimed, because of the limited
amount of guidance and limited number of working examples in Appellant’s
Specification, the nature of the invention, the state of the prior art, the
breadth of the claims and the unpredictable nature of the art at the time of
invention. Final Act. 4. The Examiner further bases this conclusion due to
the quantity of experimentation necessary to identify specific combination of
antibiotics and probiotics for specific patients with specific diseases, the
limited amount of guidance and limited number of working examples in the
specification directed to treatment while preventing C. difficile infection, the
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unpredictable nature of an invention directed to the use of generic bacterial
species as probiotics in combination with any and all antibiotics, the
unpredictability in the art with regard to probiotics and breadth of the
present claims directed to unlimited lists of infections, antibiotics and
generic bacterial species as probiotics. Id. (citing In re Wands, 858 F.2d
731, 737 (Fed. Cir. 1988).
Appellant argues that, contrary to the Examiner’s findings, a review of
the Wands factors illustrates that any experimentation required to perform
the methods within the full scope of the invention is not undue. App. Br. 10.
First, Appellant argues that the level of required skill in the art is
extremely high, requiring that a person of skill likely be a medical clinician
with experience in diagnosis of infections and pharmacotherapy. App. Br.
11.
Next, Appellant argues that the claims are relatively narrow in scope;
each of the treatable “non-gastrointestinal inflections” and the suitable
“antibiotics” is recited in the claims and are fairly common conditions, the
treatment of which would have been routinely encountered and/or studied by
a person of ordinary skilled person in the art.2 App. Br. 11. Similarly,
Appellant contends, the claims recite the probiotic(s) that may be used to

2 Appellant actually states that the claims recite: “fairly common
condition[s,] the treatment of which would have been routinely
encountered and/or studied by the highly skilled person in the art….” We
remind Appellant that the actual standard of enablement to be applied in an
analysis under the first paragraph of 35 U.S.C. § 112 is that of a person of
ordinary skill in the art. See, e.g., In re Fisher, 427 F.2d 833, 839
(C.C.P.A. 1970) (holding that “the scope of the claims must bear a
reasonable correlation to the scope of enablement provided by the
specification to persons of ordinary skill in the art”) (footnote omitted)).
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create the dosage form of the invention. Id. Appellant notes that the
Specification provides guidance in the form of identification of the treatable
Non-gastrointestinal infections, the suitable antibiotic(s) and/or the
probiotic(s) that one may use to create the dosage form of the invention, as
well as teaching related to the various known dosage forms that can be
prepared for use in the methods. Id.
Appellant argues further that the nature of the claimed invention is an
extension of a well-developed area of technology, viz., medical treatment of
infections using systemically administered antibiotics. App. Br. 11.
Appellant asserts that the technology from which the invention extends
cannot be characterized as nascent or frontier, rather, it is relatively
predictable and any experimentation required to optimize success of the
invention is quotidian to a medical practitioner, such as the person of skill in
the art. Id. at 11–12. According to Appellant, the technology of the
invention is no more unpredictable than the ordinarily and usual practice of
pharmacotherapy, in which variations routinely occur because of the endless
variety of patients’ current physical and physiological makeups. Id. at 12.
Appellant contends that the Examiner’s reliance upon Morrow as
establishing the unpredictability of the art is misplaced: Appellant argues
that Morrow discloses, at most, the well-understood concept that prognoses
of any type for critically ill patients in the Intensive Care Unit may be
unreliable. Id.
We are not persuaded by Appellant’s arguments.
Section 112 requires that the patent specification enable “those
skilled in the art to make and use the full scope of the claimed
invention without ‘undue experimentation’” in order to extract
meaningful disclosure of the invention and, by this disclosure,
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advance the technical arts. Because such a disclosure
simultaneously puts those skilled in the art on notice of the
enforceable boundary of the commercial patent right, the law
further makes the enabling disclosure operational as a limitation
on claim validity. “The scope of [patent] claims must be less than
or equal to the scope of the enablement. The scope of
enablement, in turn, is that which is disclosed in the specification
plus the scope of what would be known to one of ordinary skill
in the art without undue experimentation.”

Invitrogen Corp. v. Clontech Labs. Inc., 429 F.3d 1052, 1070–71 (Fed. Cir.
2005) (internal citations omitted).
In analyzing whether Appellant’s Specification discloses sufficient
guidance to permit a person of ordinary skill to practice the claimed
invention without undue experimentation, we are guided by the factors set
forth by our reviewing court in Wands. These factors include: (1) the
quantity of experimentation necessary; (2) the amount of direction or
guidance presented; (3) the presence or absence of working examples; (4)
the nature of the invention; (5) the state of the prior art; (6) the relative skill
of those in the art; (7) the predictability or unpredictability of the art; and (8)
the breadth of the claims. Wands, 858 F.2d at 737.
With respect to Wands factor (2) and (3), Appellant’s Specification
addresses the dosages of both the antibiotic component and the probiotic
component as follows:
The unit dose and the dosage regimen of each the antibiotic(s)
and the probiotic material(s) will be dictated by the specific
antibiotic(s) and probiotic material(s) selected the dosage form
and the medical particulars of the patient. In general, the unit
dose and the dosage regimen will parallel that of the antibiotic if
it were to be administered alone. For example, if the antibiotic
recommended dosage is 200 mgs at two hour intervals, the
antibiotic dosage in the formulation will remain substantially the
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same, as would the frequency of administration of the entire
formulation. However, the therapeutically effective dosage of
any specific antibiotic or agent will vary somewhat from
antibiotic to antibiotic and/or probiotic material to probiotic
material, patient to patient, and will depend upon the condition
of the patient and the dosage form.

Spec. ¶ 26. More specifically, and with respect to the probiotic component,
the Specification discloses that:
In general, the probiotic material per unit dose may be preferred
to be at about 2 billion colony forming units (CFUs) to about 50
billion CFUs, about 4 billion CFUs to about 10 billion CFUs, or
about 6 billion CFUs to about 8 billion CFUs, depending on the
medical particulars of the patient, including age and weight.

Id. ¶ 27.
Appellant’s Specification provides two predictive examples, each a
case study featuring a single patient. In Example I, “A 78 year old patient is
diagnosed with nosocomial pneumonia and is prescribed a course of
levofloxicin and probiotic material to be administered in single dose units
…. each filled capsule contain[ing] a single dose of 750mg levofloxicin and
the equivalent of 8 CFUs of probiotic material” daily for 14 days. Spec. ¶
32. In Example II, the Specification discloses a study featuring “A 5 year
old patient [ ] diagnosed with a middle ear infection” who is administered a
10 ml dose of “250 mg amoxicillin, 31.25 mg clavulonic acid in a potassium
salt, and 4 CFUs of probiotic material” daily for 10 days. Id. at ¶¶ 34–36.
With the exception of these two examples, and the additional
exemplary mention in paragraph [0026] quoted supra, Appellant’s
Specification does not disclose prescribed dosages for a given antibiotic for
a given bacterial infection. We do not, however, find this determinative,
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because the antibiotic dosage prescriptions for a given type of specific
bacterial infection are well-known in the art of medicine and would be
dependent upon the nature of the bacterial infection, the nature of the
antibiotic, the age, health, size, and gender, etc., of the individual patient.
The prescription of antibiotics for a given type of infection is routine and
certainly well understood by practitioners of ordinary skill in the art of
medicine (Wands factors 4–7).
The disclosures of the Specification with respect to the probiotic
component of the claims, however, presents us with a conundrum. The
Specification describes individual dosage units of “2 billion colony forming
units (CFUs) to about 50 billion CFUs, about 4 billion CFUs to about 10
billion CFUs, or about 6 billion CFUs to about 8 billion CFUs, depending on
the medical particulars of the patient, including age and weight.” Spec. ¶ 27.
However, the two individual case studies presented in Examples I and II
consist of daily dosages of 8 and 4 CFUs3 respectively, a very considerable
disparity from the preferred dosages disclosed in paragraph [0027].
We find this large disparity between the preferred ranges recited in
paragraph [0027] of the Specification, and those actually administered in the
Specification’s Examples I and II to be so wide (more than 9 orders of
magnitude) so as to provide little reliable guidance to a practitioner of
ordinary skill in the art, even as we acknowledge that a general dosage range
for probiotics may well be generally known in the art. We conclude that, to
practice the claimed invention successfully, a practitioner of ordinary skill,

3 We note that if these dosages are in error, a fact not clearly in evidence of
record, correction should avoid the inclusion of new matter.
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confronted with a vast range of possible dosages – between 4 CFUs and 8
billion CFUs – would necessarily have to perform an undue amount of
experimentation to find the proper dosage required to practice the invention.
We consequently affirm the Examiner’s rejection upon this ground.

B. Rejection of claims 93–118 under 35 U.S.C. § 103(a)
Issue 1: claims 93–104, 117, and 118
Appellant argues that the Examiner erred in finding that the combined
cited prior art references teach or suggest a method using a single dosage
form (containing both probiotic and antibiotic) to act systemically to treat a
non-gastrointestinal infection and to prevent a C. difficile infection in the GI
tract. App. Br. 16.

Analysis
The Examiner finds that Witsell and Arvola each teach methods of
treatment with combined antibiotic-probiotic therapies of patients having
nongastrointestinal infections and/or disorders while preventing
gastrointestinal disorders, including antibiotic-associated diarrhea caused by
infections, including by C. difficile infection. Final Act. 5.
Specifically, the Examiner finds that Witsell teaches that treatment of
middle ear infections, in which concomitant administration of a probiotic
bacteria Lactobacillus acidophilus together with two antibiotics, amoxicillin
and clavulanate, is associated with a significant decrease in patient
complaints of gastrointestinal effects during antibiotic therapy for
otolaryngology patients. Final Act 5–6 (citing Witsell Abstr.). The
Examiner finds that Witsell expressly teaches that patients were diagnosed
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with otitis media, sinusitis and/or bacterial pharyngitis, and given antibiotic
therapy for these conditions. Id. at 6 (citing Witsell 231). The Examiner
also finds that Witsell additionally teaches that simultaneous administration
of a probiotic with the antibiotic prevents and/or minimizes gastrointestinal
infection by C. difficile. Id. The Examiner finds that Witsell teaches that the
combined therapy resulted in a significant decrease in patient complaints of
gastrointestinal effects during antibiotic therapy in patients with
otolaryngological problems. Id.
The Examiner finds that Arvola teaches treatment of patients with
pneumonia and middle ear infection by concomitant or simultaneous
administration of a probiotic bacteria Lactobacillus rhamnosus with
antibiotics, including penicillin, amoxicillin, cephalosporin, erythromycin,
trimethoprim. Final Act. 6. The Examiner finds that administration of this
therapy to patients with respiratory infections associated with otitis,
pneumonia, bronchitis significantly reduced the incidence of antibiotic-
induced disturbances of intestinal flora and diarrhea. Id. (citing Arvola, e.g.,
Table 1). The Examiner also finds that Arvola teaches that analysis of fecal
samples in the treated patients for C. difficile demonstrated that only 2 cases,
(out of 199 patients), were found positive or C. difficile, indicating
prevention of C. difficile infections. Id. at 6–7.
The Examiner finds that, although Witsell and Arvola teach
concomitant and simultaneous administration of antibiotics and probiotics,
neither reference teaches that “the antibiotic and probiotic material are in
physical contact with one another in the formulation,” as recited in claim 93.
Final Act. 7. However, the Examiner finds, it was well known in the art at
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the time of invention to provide both an antibiotic and a probiotic in the
same one formulation. Id.
By way of example, the Examiner points to Fitzpatrick, which teaches
co-administration of the probiotic bacteria E. coli and antibiotic(s) in one
formulation, such as the same tablet or in a suspension. Final Act. 7 (citing
Fitzpatrick ¶¶ 145, 153).
The Examiner also cites Farmer, which the Examiner finds teaches
co-administration of the probiotic bacteria Bacillus coagulans and broad-
spectrum antibiotic(s) in one formulation or in the same tablet/capsule.
Final Act. 7 (citing Farmer col. 23, ll. 44–48). The Examiner finds that
Farmer teaches that the probiotic in the formulation minimizes
gastrointestinal infections including, C. difficile. Id. (citing Farmer col. 8, ll.
51–59).
The Examiner therefore concludes that it would have been obvious to
a person of ordinary skill in the art to modify the co-administration methods
of Witsell and Arvola by using a single formulation containing both
antibiotic and probiotic components in contact with each other. Final Act.
7–8. The Examiner further concludes that a skilled artisan would have had a
reasonable expectation of success in so modifying the methods of Witsell
and Arvola, because both Farmer and Fitzpatrick teach the use of a single
dose formulation of antibiotic and probiotic constituents. Id. at 8.
Appellant argues that Witsell and Arvola are each silent with respect
to contemporaneous ingestion of the separate dosage forms of antibiotic and
probiotic so that both forms are present in the gut at the same time, as is the
consequence of the claimed method. App. Br. 16.
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Appellant argues that neither Farmer nor Fitzpatrick cure the alleged
deficiencies of Witsell or Arvola. App. Br. 16. According to Appellant,
Farmer is directed to methods of treating infections at, and closely adjacent
to the, the location where the therapy is applied. Id. at 16–17 (citing, e.g.,
Farmer col 8, ll. 41–63 (teaching that the Farmer method is directed to
infections of the gastrointestinal tract); col. 11, ll. 55–57 (teaching treatment
of vaginal infections by applying intra-vaginally); col. 11, ll. 61–65 (treating
skin infections by applying topically to skin); col. 26, ll. 24–29 (treating oral
infections by applying directly to the oral cavity).
Similarly, Appellant argues, Fitzpatrick teaches localized treatment in
the GI track of anaerobe bacterial infection, such as microbial infection,
irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and
pouchitis, which are caused by anaerobic bacteria. App. Br. 17.
We are not persuaded by Appellant’s arguments. Arvola teaches that:
Antibiotic use was continued for 7 to 10 days, and the dosage
was divided into two or three doses and given every 8 to 12
hours. The patients were randomized by means of a computer
program to receive placebo (microcrystalline cellulose) in
capsule or 2 x 1010 colony-forming units of Lactobacillus GG in
capsules given twice daily during the antimicrobial treatment.

Arvola 2. We agree with Appellant that Arvola does not expressly teach that
the antibiotic and probiotic were administered simultaneously, nevertheless,
the reference does teach that the constituents were administered on or about
the same schedule over the course of the study. More importantly, there is
no teaching or suggestion by Arvola indicating any reason why the antibiotic
and probiotic could or should not be administered at the same time.
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Similarly, Witsell teaches that:
[All patients] were counseled by the nursing staff to take the
amoxicillin/clavulanate three times a day with food and eat a
normal, balanced diet. Patients entered in the Augmentin-and-
Lactinex group were also instructed to take the Lactinex (L.
acidophilus and L. bulgaricus) as three tablets, four times daily
(1.2 x 108 organisms/day).

Witsell 231. Again, although Witsell does not expressly teach simultaneous
administration of antibiotics and probiotics, it teaches “concomitant
administration” (Witsell 232) of the two on similar schedules and, again,
there is no teaching or suggestion of Witsell that antibiotics and probiotics
could not, for the sake of convenience, have been administered
simultaneously.
Farmer teaches:
The present invention is discloses the recent discovery that non-
pathogenic, lactic acid-producing bacterial species (i.e.,
“probiotic bacteria”), such as the exemplary Bacillus coagulans,
may be utilized in combination with antibiotic compounds or
other functional anti-microbial drugs and supplements so as to
form therapeutic compositions for use in ameliorating and/or
controlling the colonization of pathogenic bacteria with the
gastrointestinal tract of both humans and animals.

Farmer col. 10, ll. 51–59. Farmer also teaches that: “In a preferred
embodiment, Bacillus coagulans spores, a therapeutically-effective
concentration of an antibiotic, antifungal, etc., and, if so desired, various
other components (e.g., bifidogenic oligosaccharide, binders, etc.) are
encapsulated.” Id. at col. 23, ll. 44–49. Finally, Farmer teaches that:
In preferred embodiments of the present invention, the Bacillus
coagulans strain is combined with a therapeutic dose of an
antibiotic such as Gentamicin; Vancomycin; Oxacillin;
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Tetracyclines; Nitroflurantoin; Chloramphenicol; Clindamycin;
Trimethoprim-Sulfamethoxasole; a member of the Cephlosporin
antibiotic family (e.g., Cefaclor, Cefadroxil, Cefixime,
Cefprozil, Ceftriaxone, Cefuroxime, Cephalexin, Loracarbef,
and the like); a member of the Penicillin family of antibiotics
(e.g., Ampicillin, Amoxicillin/Clavulanate, Bacampicillin,
Cloxicillin, Penicillin VK, and the like); with a member of the
Fluoroquinolone family of antibiotics (e.g., Ciprofloxacin,
Grepafloxacin, Levofloxacin, Lomefloxacin, Norfloxacin,
Ofloxacin, Sparfloxacin, Trovafloxacin, and the like); or a
member of the Macrolide antibiotic family (e.g., Azithromycin,
Erythromycin, and the like).

Id. at col. 23, ll. 18–33. We note that this list of antibiotics overlaps heavily
with that recited both in Appellant’s claims (see claims 95–99, 107–111) for
treatment of non-gastrointestinal diseases, but also include the antibiotics
used in Arvola and Witsell for treatment of non-gastrointestinal diseases.
Just as importantly, we find no teaching in Farmer expressly limiting
the co-administration of probiotics and antibiotics at, or closely adjacent to
the, the location where the therapy is applied, as Appellant argues. See, e.g.,
Farmer claim 1, which recites:
1. A method for reducing gastrointestinal colonization by a
pathogenic Clostridium bacterium, comprising identifying a
mammalian subject having an infection with said pathogenic
Clostridium bacterium, and orally administering a
therapeutically-effective concentration of Bacillus coagulans
bacteria within a pharmaceutically-acceptable carrier suitable for
administration to the gastrointestinal tract of said subject, and
further comprising the administration of a therapeutically-
effective dose of an antibiotic, wherein the Bacillus coagulans
bacteria reduce colonization of the pathogenic Clostridium
bacteria.

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Farmer teaches that the aim of its invention is to protect the bacterial
infauna of the gastrointestinal tract from the deleterious effect, well-known
in the art, of, inter alia, antibiotic therapy: “While the gastrointestinal
microflora presents a microbial-based barrier to invading organisms,
pathogens often become established when the integrity of the microbiota is
impaired through stress, illness, antibiotic treatment, changes in diet, or
physiological alterations within the G.I. tract.” Farmer col. 2, ll. 49–53
(emphasis added).
Appellant points to the various exemplary embodiments where the
antibiotics and probiotics may be administered locally, but such examples do
not define the scope of the claims. See Merck & Co., Inc. v. Biocraft Labs.,
Inc., 874 F.2d 804, 807 (Fed. Cir. 1989) (holding that “all disclosures of the
prior art, including unpreferred embodiments, must be considered”). Rather,
we understand the exemplary embodiments of Farmer as demonstrating the
flexibility of simultaneous probiotic and antibiotic administration in
different applications.
Similarly, Fitzgerald teaches that:
The present invention is of a novel biotherapeutic composition
containing a probiotic bacterial strain and an antibiotic to which
the bacterial strain is resistant, which can be efficiently used in
treating or preventing a condition caused by anaerobic bacteria.
Specifically, the present invention is of a novel biotherapeutic
composition, which comprises a probiotic Escherichia coli strain
and an anaerobic bacteria antibiotic such as metronidazole, and
of uses thereof in the treatment of gastrointestinal disorders such
as pouchitis.

Fitzgerald ¶ 98. We acknowledge that Fitzgerald makes specific reference
to diseases of the gastrointestinal tract, but Appellant points to no teaching
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or suggestion of Fitzgerald that limits its invention to such applications. See,
e.g., Fitzgerald claim 1.
In the larger sense, however, Appellant’s argument rather misses the
point of the Examiner’s rejection. Arvola and Witsell teach that probiotics
and antibiotics can be co-administered on a daily basis for the treatment of
non-gastrointestinal diseases while also protecting the gastrointestinal tract
from C. difficile infections. The Examiner relies upon Farmer and Fitzgerald
as showing that probiotics and antibiotics can be combined into a single dose
without the constituents having adverse effects upon each other. “[I]t was
manifestly obvious to combine two well-known drugs—which had
previously been administered together—in a single tablet.” Ortho-McNeil
Pharm., Inc. v. Teva Pharm. Industries, Ltd., 344 Fed. Appx. 595, 602 (Fed.
Cir. 2009). We agree with the Examiner’s conclusion that it would have
been obvious to combine the teachings of the references to arrive at
Appellant’s injection.

Issue 2: claims 105–116
Appellant argues that the Examiner erred because the combined cited
prior art neither teaches nor suggests:
[U]se of a single dosage form (containing both probiotic and
antibiotic) to act to systemically treat a non-GI infection and to
prevent a Clostridium difficile infection in the GI tract, where the
non-GI infection is one caused by [any one or more of]
Haemophilus influenzae, Haemophilus parainfluenzae,
Moraxella catarrhalis, Staphylococcus aureus, Staphylococcus
epidermidis, Staphylococcus saprophyticus, Pseudomonas
aeruginosa, Serratia marcescens, Escherichia coli, Klebsiella
pneumoniae, Streptococcus pneumoniae, Streptococcus
pneumonia parainfluenzae, Streptococcus pyogenes, Chlamydia
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pneumoniae, Legionella pneumophila, Mycoplasma
pneumoniae, Vibrio cholerae, Bacillus anthracis, Eikenella
corrodens, Neisseria gonorrhoeae, Enterococcus faecalis,
Enterobacter cloacae, Proteus mirabilis, bacteria of the genus
Bacteroides, including Bacteroides fragilis, bacteria of the genus
Fusobacterium, and bacteria of the genus Peptostreptococcus, as
recited in the claims 105–116.

App. Br. 17–18.

Analysis
Appellant argues that Witsell, Avola, and Farmer are silent on the
pathogens infecting the patients in their studies. App. Br. 18. Appellant also
notes that Fitzpatrick discloses bacterial pathogens, but only for the
gastrointestinal infections its composition is intended to treat. Id.
The Examiner responds, by way of example, that Witsell teaches
treatment of patients with sinusitis; and that sinusitis is commonly caused
infections of bacterial origin including claimed Streptococcus pneumoniae,
Haemophilus influenzae, and Moraxella catarrhalis. Ans. 15.
We agree with the Examiner. Witsell teaches treatment of patients
with bacterial infections including otitis media, pharyngitis, and sinusitis.
Witsell 231. It is generally well known in the medical arts generally that
certain bacteria are commonly associated with sinusitis, including
Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella
catarrhalis. See, e.g., Spec. ¶ 30. We are consequently no persuaded by
Appellant’s argument.

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Issue 3
Appellant argues that the Examiner erred because a person of ordinary
skill in the art would not have been motivated to combine the references to
arrive at the invention recited in claims 93–118. App. Br. 18.

Analysis
Appellant argues that the methods of both Farmer and Fitzpatrick are
intended for the treatment of a gastrointestinal tract infection or disorder that
already exists, and that neither discloses a method that simultaneously treats
a non-gastrointestinal tract infection or any non-gastrointestinal infection at
all. App. Br. 18. Appellant also argues that neither Witsell nor Arvola teach
a dosage containing the two claimed components, or that the
antibiotic/antimicrobial should be taken contemporaneously with the
probiotic. Id. Appellant argues further that neither reference teaches that
contemporaneous co-administration is necessary or beneficial for any
reason. Id.
Furthermore, Appellant contends, Arvola teaches away from use of
probiotics to treat or prevent CD infection, because it explicitly discloses
that the best method of treating such infection is still “use of
[anti]microbials,” which are locally administered into the gastrointestinal
tract. App. Br. 18.
We are not persuaded by Appellant’s arguments. As an initial matter,
a reference can be said to teach away from an invention when “a person of
ordinary skill, upon reading the reference, would be discouraged from
following the path set out in the reference, or would be led in a direction
divergent from the path that was taken by the applicant.” In re Gurley, 27
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F.3d 551, 553 (Fed. Cir. 1994). However, teaching an alternative or
equivalent method, however, does not teach away from the use of a claimed
method. In re Dunn, 349 F.2d 433, 438 (C.C.P.A. 1965).
The passage of Arvola quoted by Appellant reads, in its entirety:
“The most effective way to prevent antibiotic-associated diarrhea is still
critical use of antimicrobials, as recommended recently for the treatment of
acute otitis media in children. However, when antimicrobial treatment is
indicated, Lactobacillus GG is a safe and useful adjunctive therapy to
prevent diarrhea.” Arvola 3–4. In other words, Arvola expressly
recommends a combination of antimicrobial and probiotic in the treatment
of diarrhea associated with the treatment of a non-gastrointestinal infection
(otitis media) in children. We conclude that this does not constitute a
“teaching away” by the Arvola reference.
With respect to the motivation to combine the references, Appellant
contends that neither Witsell nor Arvola teaches or suggests that
contemporaneous co-administration is necessary or beneficial for any
reason. This is not the standard that we apply in determining obviousness;
rather, it is what the combination of references would have taught or
suggested to the person of ordinary skill in the art. See, e.g., In re Chevalier,
500 Fed. App’x 932, 934 (Fed. Cir. 2013).
We agree with the Examiner that Witsell and Arvola both teach
concomitant administration of antibiotics and probiotics in the treatment of
non-gastrointestinal bacterial infections as a way of protecting against
related gastrointestinal infection of C. difficile. Both Farmer and Fitzpatrick
teach that antibiotics and probiotics can be combined into a single dosage
form in which the constituents are in physical contact with each other. We
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conclude, together with the Examiner, that a person of ordinary skill in the
art would have been motivated, when considering treatment of non-
gastrointestinal tract infections, to physically combine the antibiotic and
probiotic to be administered into a single dosage form, to improve patient
convenience and effective compliance with the regime and to prevent or
minimize possible C. difficile infection.

Issue 4
Appellant argues that the Examiner erred because secondary
considerations of nonobviousness are sufficient to overcome the Examiner’s
conclusion that the claims are prima facie obvious. App. Br. 18.
Analysis
Appellant first argues that the claimed invention satisfies a long-felt,
though hitherto unrealized need. App. Br. 19. In support of this contention,
Appellant points to the Declaration of Dr. Scott Dorfner, D.O. (the “Dorfner
Declaration”), filed on March 30, 2017.4 Id. According to Appellant, the
inventive methods satisfy a long felt need for a way to prevent development
of a C. difficile infection when undergoing systemic antibiotic treatment for
a non-gastrointestinal infection that is clinically and practically effective. Id.
By “clinically effective,” Appellant means that the prevention of a C.
difficile infection occurs. App. Br. 19. By “practically effective,” Appellant
means that patients are able to comply with the binary dosage routine. Id.
Appellant argues that “clinical medical practice” involves treating patients
experiencing minor infections of various anatomical regions, excluding

4 Dr. Dorfner is the inventor of record of the claimed invention on appeal.
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infections of the gastrointestinal tract. Id. Appellant asserts that Dr. Dorfner
states, by way of example, that an average general medical practice may see
up to 15–20 patients per day with non-gastrointestinal tract infections,
including, e.g., bronchitis, sinusitis, ear or eye infections, wound or skin
infections, animal bite infections, pneumonia, nail infections, acnes,
bacterial infections of a sexually transmitted origin, and urinary tract
infections. Id. (citing Dorfner Decl. ¶ 13).
Appellant cites the Dorfner Declaration as providing an overview of
how C. difficile infections constitute a common and harmful side effect of
treating patients with non-gastrointestinal infections with antibiotics;
Appellant contends that it is therefore apparent that the challenge of
preventing C. difficile infection in patients undergoing a course of systemic
antibiotic treatment for a non-gastrointestinal infection has been well
appreciated for many years. Id. at 19–20 (citing Dorfner Decl. ¶¶ 15–20).
Appellant notes that the prior art, including Witsell and Arvola,
teaches using administration of probiotics to prevent C. difficile infections
have been made by providing probiotic supplements to patients undergoing
antibiotic therapy. App. Br. 20. Appellant asserts that, in a clinical context,
patients undergoing antibiotic treatment for infections are often unwilling or
unable to take probiotic supplements, even when advised to do so by their
prescribing doctor. Id. at 21.
Appellant points out that Arvola was published in 1999, and Witsell in
1995 and teaches other similar experiments dating back to the early 1990s.
App. Br. 21. According to Appellant, in the ensuing 25-plus years since
these experiments, no one has developed the claimed method which includes
administration of the binary dosage form (i.e., a binary dosage form with
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antibiotic and probiotic in contact with one another). Id. This, Appellant
argues, is possibly due to the commonly held conception in the art that
mixing an antibiotic with a probiotic would effectively react with or kill the
probiotic, rendering it therapeutically useless. Id. Therefore, argues
Appellant, no person of skill in the art considered a binary form as a
potential solution to the two-fold problem of preventing C. difficile infection
and increasing/improving patient compliance, prior to Appellant’s invention.
Id. (citing Dorfner Decl. ¶ 27).
We are not persuaded by Appellant’s argument in this respect.
Appellant’s argument that there was a long-felt and hitherto unmet demand
for their invention is entirely inferential and not supported by objective
evidence of record; even Dr. Dorfner’s opinion is not supported by any
objective indicia of a long-felt need for the claimed invention.
Where, as here, the obviousness determination turns on whether
one of ordinary skill in the art would have expected that a
particular formulation of an extended-release drug would be
successful—in other words, would render a therapeutically
effective treatment—objective indicia of failure of others and
longfelt need are particularly telling.

In re Cyclobenzaprine Hydrochloride Extended-Release Capsule Patent
Litig., 676 F.3d 1063, 1083 (Fed. Cir. 2012) (emphasis added). We accord
due weight to Dr. Dorfner’s explanation that secondary gastrointestinal C.
difficile infections represent a medical problem, although we also note that
Dr. Dorfner’s statements to this effect are entirely unsupported by objective
evidence of record. Nor does the Dorfner Declaration, or Appellant, provide
objective evidence of a long-felt need, or evidence that others have
unsuccessfully attempted to make or apply the solution Appellant claims for
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its invention. In the absence of any such objective evidence of record, we do
not find Appellant’s arguments that its invention answers a long-felt need
are persuasive.
Appellant next argues that, over the past five years, and in clinical
experience with hundreds of patients, Dr. Dorfner has formulated and
compounded multiple antibiotics for treatment of non-gastrointestinal
infections with multiple species of probiotics into a single delivery system
which patients have successfully used in the practice of the claimed method
to avoid C. difficile infections. App. Br. 21 (citing Dorfner Decl. ¶ 29).
Appellant argues that it was observed that gastrointestinal side effects,
including antibiotic-associated diarrhea have been almost completely
eradicated. Id. at 22. In addition, asserts Appellant, patient compliance and
completion of therapy was also markedly improved, and the incidence of C.
difficile infection and colitis, secondary to the administration of oral
antibiotics, has also been significantly and vastly reduced in low, medium,
and high-risk patients. Id.
We are not persuaded by Appellant’s argument that the argued effects
with respect to prevention and improved patient compliance constitute
sufficient objective of surprising or unexpected results sufficient to
overcome the Examiner’s prima facie conclusion of obviousness. Again, we
note that the Dorfner Declaration provides no objective evidence beyond Dr.
Dorfner’s unsupported assertions. See Dorfner Decl. ¶¶ 29–30. “It is well
settled that unexpected results must be established by factual evidence. Mere
argument or conclusory statements … [do] not suffice.” In re Soni, 54 F.3d
746, 750 (Fed. Cir. 1995) (citation omitted). Neither Appellant’s Brief nor
the Dorfner Declaration cite any such objective evidence of record. See In
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re Am. Academy of Sci. Tech Center, 367 F.3d 1359, 1370 (Fed. Cir. 2004)
(“[T]he Board is entitled to give such weight to declarations as it deems
appropriate.”)
Furthermore, “when unexpected results are used as evidence of
nonobviousness, the results must be shown to be unexpected compared with
the closest prior art.” In re Baxter Travenol Labs., 952 F.2d 388, 392 (Fed.
Cir. 1991). Appellant points to no such comparison of their allegedly
unexpected or surprising results with any prior art of record. As such, we
conclude that, in the absence of any objective evidence supporting the
argument that Appellant’s results are surprising or unexpected has little or
no probative value, and we affirm the Examiner’s rejection of the claims.

CONCLUSION
The Examiner’s rejection of claims 93–116 under 35 U.S.C.
§ 112, first paragraph, is affirmed.
The Examiner’s rejection of claims 93–118 under 35 U.S.C.
§ 103(a) 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)(iv).

AFFIRMED

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Claims
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
93–116 112, first
paragraph
Enablement 93–116
93–118 103(a) Witsell, Arvola,
Farmer, Fitzpatrick
93–118
Overall
Outcome
93–118