ZAMBON S.P.A.

Patent Trials and Appeals Board

Aug 20, 2020

2020001434 (P.T.A.B. Aug. 20, 2020)

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.
14/356,650 05/07/2014 Alberto Moretto SS917.1003 4556
122515 7590 08/20/2020
Silvia Salvadori, P.C.
Silvia Salvadori
485 Central Park West Unit 5C
New York, NY 10025
EXAMINER
LEE, ANDREW P
ART UNIT PAPER NUMBER
1628
NOTIFICATION DATE DELIVERY MODE
08/20/2020 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):
eofficeaction@appcoll.com
silvia30121@me.com
silvia@salvadorilaw.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
________________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
________________

Ex parte ALBERTO MORETTO,
ALESSANDRA DE LAZZARI, and LUCIA DICORATO1
________________

Appeal 2020-001434
Application 14/356,650
Technology Center 1600
________________

Before ERIC B. GRIMES, JOHN G. NEW, and JAMIE T. WISZ,
Administrative Patent Judges.

NEW, Administrative Patent Judge.

DECISION ON APPEAL

1 We use the term “Appellant” to refer to the “applicant” as defined in
37 C.F.R. § 1.142. Appellant states that the real party-in-interest is
ZAMBON S.P.A. App. Br. 3.
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SUMMARY
Appellant files this appeal under 35 U.S.C. § 134(a) from the
Examiner’s Non-Final Rejection of claims 1–5, 7–11, 14–15, and 22 as
unpatentable under 35 U.S.C. § 103(a) as being obvious over Gruber (US
2009/0175940 A1, July 9, 2009) (“Gruber”).
We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.

NATURE OF THE CLAIMED INVENTION
Appellant’s invention is directed to a pharmaceutical, non-
effervescent, solid composition comprising a mixture of a pharmaceutically
effective amount of a ibuprofen salt and a pharmaceutically acceptable
strong base in a molar ratio of from 1.0:0.01 to 1.0:0.8. Abstr.

REPRESENTATIVE CLAIM
Claim 1 is representative of the claims on appeal and recites:
1. A pharmaceutical, non-effervescent, solid composition for
immediate oral administration previous dissolution in drinkable
water, said composition consisting essentially of

a mixture of a pharmaceutically effective amount of an
ibuprofen salt and a pharmaceutically acceptable base in a molar
ratio of from 1:0.01 to 1:0.8, wherein the base is selected from
an alkaline metal carbonate, an alkaline metal hydroxide and a
tribasic metal phosphate; and

one or more pharmaceutically acceptable excipients
selected from the group consisting of preservative agents,
diluting agents, sweeting agents, aromatic agents and artificial
colors,
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said composition being such that, when dissolved in said
drinkable water for dilution, imparts a pH value ranging from 9.0
to 9.5 to the obtained solution,

said pH range masking ibuprofen taste in said water
solution, avoiding sensory irritation to the oral cavity when
swallowed.

App. Br. 14.

ISSUE AND ANALYSIS
We adopt the Examiner’s reasoning, findings of fact, and conclusions
that the appealed claims are obvious over the cited prior art. We address the
arguments raised by Appellant below.

Issue 1
Appellant argues the Examiner erred because the cited prior art does
not teach or suggest Appellant’s invention. App. Br. 7.

Analysis
The Examiner finds that Gruber teaches compositions comprising
solubilized ibuprofen granulate and a base such as sodium carbonate or
sodium hydroxide. Non-Final Act. 5 (citing Gruber ¶¶ 64–66). The
Examiner also finds that Gruber teaches granulates suitable for sachets that
may also contain sweeteners. Id. (citing Gruber ¶ 85). The Examiner also
finds that Gruber teaches providing enough base to provide a pH of at least
7.5. Id. (citing Gruber ¶ 89).
The Examiner acknowledges that Gruber does not expressly teach
compositions with a pH of 9.0–9.5. Non-Final Act. 5. However, the
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Examiner concludes that it would have been obvious to person of ordinary
skill in the art to optimize the constituent concentrations to arrive at the
claimed pH range, according to the guidance provided by Gruber. Id. at 6
(citing In re Aller, 220 F.2d 454, 456 (C.C.P.A. 1955) (holding that “where
the general conditions of a claim are disclosed in the prior art, it is not
inventive to discover the optimum or workable ranges by routine
experimentation”)).
Appellant argues that Gruber provides only for pharmaceutical solid
compositions in which ibuprofen is in its native acidic form, and is first
reacted with a base to obtain a salt. App. Br. 7 (citing, e.g., Gruber ¶ 28).
Specifically, Appellant asserts that paragraph [0028] of Gruber teaches that
“[i]t has surprisingly been found that a solubilized ibuprofen can be directly
obtained in one step by reacting ibuprofen with a base in essentially dry
state.” Id. In other words, contends Appellant, the paragraphs of Gruber
relied upon by the Examiner refer to solubilized ibuprofen granulate
comprising a mixed sodium and potassium salt of ibuprofen. Id. (citing
Gruber ¶¶ 35, 61). Appellant therefore asserts that Gruber teaches the
ibuprofen salt only.
In contrast to the teachings of Gruber, argues Appellant, the claimed
composition is directed to a mixture of ibuprofen salt with a base, and not to
just an ibuprofen salt, as allegedly taught by Gruber. App. Br. 7. According
to Appellant, the difference between the claimed invention and the prior art
is that, in Appellant’s invention, the base is utilized to alkalinize the solution
of the ibuprofen salt, whereas Gruber teaches that the base has the function
of reacting stoichiometrically with ibuprofen in its native acidic form to
obtain a soluble ibuprofen salt. Id.
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In support of this contention, Appellant points to the Declaration of
Dr. Alberto Moretto (the “Moretto Declaration”), filed March 13, 2018.
App. Br. 8. Dr. Moretto attests that:
[T]he pharmaceutical solid compositions described by Gruber
only refer to mixtures of ibuprofen in its native acidic form with
a base. In contrast, the pharmaceutical composition presently
claimed is a mixture of ibuprofen salt with a base.

Thus, in the present application the base is utilized only to
alkalinize the solution of the ibuprofen salt, while in Gruber the
base has the function of reacting stoichiometrically with
ibuprofen in its native acidic form to obtain a soluble ibuprofen
salt.
….

In other words, in Gruber the ibuprofen salt is the result obtained
by adding a base to ibuprofen in its native acidic form in order to
obtain a soluble form of ibuprofen. On the other hand, in the
present application a base is added to the ibuprofen salt to obtain
a soluble form of ibuprofen which does not cause oral cavity
irritation during therapy.

Moretto Decl. ¶¶ 14–17.
We are not persuaded by Appellant’s arguments. Appellant contends
that “the pharmaceutical solid composition presently claimed is directed to a
mixture of ibuprofen salt with a base, not to just ibuprofen salt as described
in Gruber,” and that Gruber’s “ibuprofen salt is the result obtained by adding
a base to ibuprofen in its native acidic form in order to obtain a soluble form
of ibuprofen.” See App. Br. 7; Moretto Decl. ¶ 17. We agree with
Appellant that Gruber teaches that “a solubilized ibuprofen can be directly
obtained in one step by reacting ibuprofen with a base in essentially dry
state.” Gruber ¶ 28.
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Gruber also specifies that: “In the scope of the present invention, the
term ‘solubilized ibuprofen’ means water-soluble forms of ibuprofen
wherein at least part of the ibuprofen is present in salt form. Unless indicated
otherwise, ‘ibuprofen’ refers to the racemic acid form 2-(4-isobutylphenyl)
propionic acid.” Gruber ¶ 35. So we are in agreement with Appellant,
insofar as that Gruber thus teaches that solubilized ibuprofen is synthesized
by combining the free-acid form with a base to produce an ibuprofen salt.
However, Gruber also teaches:
Another aspect of the present invention is a pharmaceutical
composition comprising a solubilized ibuprofen or solubilized
ibuprofen granulate [i.e., the ibuprofen salt] prepared by the
process of the present invention. This pharmaceutical
composition may in addition to the solubilized ibuprofen or
ibuprofen granulate also comprise a basic compound which is
preferably selected form the group consisting of sodium and/or
potassium hydrogencarbonate, sodium carbonate, potassium
carbonate, tribasic sodium and potassium phosphates and
mixtures thereof. The pharmaceutical compositions may also
comprise one or more pharmaceutically acceptable excipients
which are usual for ibuprofen-based compositions.

Gruber ¶ 66 (emphasis added). Gruber thus teaches a composition that, in
addition to “an ibuprofen salt” (i.e., the solubilized ibuprofen), also contains
a base which can be “an alkaline metal carbonate” (i.e., sodium and/or
potassium hydrogen carbonate, sodium carbonate, potassium carbonate) or a
“tribasic metal phosphate” (i.e., tribasic sodium and potassium phosphates),
as required by claim 1.2 We are consequently not persuaded by Appellant’s

2 See also Gruber claims 61 and 62 (emphases added):
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arguments that Gruber does not teach a combination of ibuprofen salt and an
alkali metal base.

Issue 2
Appellant argues that the Examiner erred because Gruber, unlike
Appellant’s claimed invention, uses weak bases rather than strong bases, as
claimed. App. Br. 11.

Analysis
Appellant argues that Appellant’s claims employ strong bases, rather
than the weak bases allegedly employed by Gruber. App. Br. 11; see also
Moretto Decl. ¶ 13 (“The invention is directed to a combination of ibuprofen
salt and a strong base….”). Appellant points to pH (Titration) Curves, filed
October 1, 2018 (“pH Curves”), as demonstrating that strong bases reach
alkaline pH (9–9.5) faster and with lower volumes than weak bases. Id.
Appellant contends that pH Curves teaches that a buffer solution is formed

61. A pharmaceutical composition comprising the solubilized
ibuprofen of claim 51.

62. The pharmaceutical composition of claim 61, comprising additionally
a basic compound selected from the group consisting of sodium
and/or potassium hydrogencarbonate, sodium carbonate, potassium
carbonate, tribasic sodium and potassium phosphates and mixtures
thereof.

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when weak bases are added to strong acids, i.e., ibuprofen. Id. at 12 (citing
pH Curves 53).
Appellant argues that pH Curves thus teaches that a buffer solution is
formed containing an excess of the weak base and of its salt that resists any
large increase in pH. Id. Appellant contends that a person of ordinary skill
in the art would not have found it obvious to adjust the pH of the
composition, nor would it have been routine to adjust the pH levels to the
claimed pH range with a reasonable expectation of success. Id.
We disagree. As an initial matter, Appellant’s claims do not recite
“strong bases.” Claim 1, the only independent claim on appeal, recites “a
mixture of a pharmaceutically effective amount of an ibuprofen salt and a
pharmaceutically acceptable base … wherein the base is selected from an
alkaline metal carbonate, an alkaline metal hydroxide and a tribasic metal
phosphate.” As we have explained supra, Gruber teaches compositions of
an ibuprofen salt and an alkaline metal carbonate (i.e., sodium and/or
potassium hydrogen carbonate, sodium carbonate, potassium carbonate) or a
tribasic metal phosphate (i.e., tribasic sodium and potassium phosphates).
See Gruber ¶ 66. Gruber thus expressly teaches two of the bases directly
recited by the claims as the group of bases to be combined with an ibuprofen
salt. We are consequently not persuaded that Gruber does not teach this
limitation of the claims.

3 pH Curves has no page numbering. We consequently refer to the page
number as being the number of the page in numerical order, with the first
page designated as page “1.”
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Issue 3
Appellant argues that the Examiner erred in finding that Gruber
teaches the limitation of claim 1 reciting “a mixture of a pharmaceutically
effective amount of an ibuprofen salt and a pharmaceutically acceptable base
in a molar ratio of from 1:0.01 to 1:0.8.” App. Br. 12.

Analysis
Appellant repeats the argument, presented supra, that Gruber
describes the ratio between ibuprofen and a base, and not the ratio between
an ibuprofen salt and a pharmaceutically acceptable base as in the presently
claimed invention. App. Br. 12. Appellant therefore argues that there are no
similarities between Appellant’s claimed composition and those taught by
Gruber. Id.
We are not persuaded. As we have explained, Gruber expressly
teaches compositions comprising solubilized ibuprofen (i.e., the ibuprofen
salt) and, additionally, bases within the groups that are expressly recited in
the claim. See Gruber ¶ 66. We consequently find no merit in Appellant’s
argument that there are no similarities between the teachings of Gruber and
the claimed compositions.

Issue 4
Appellant argues that the surprising and unexpected results of the
claimed composition overcome the Examiner’s prima facie conclusion of
obviousness. App. Br. 6.

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Analysis
Appellant argues that the addition of a strong, pharmaceutically
acceptable base, i.e., an alkaline metal carbonate, an alkaline metal
hydroxide, or a tribasic metal phosphate, unexpectedly removes oral cavity
irritation when the solid composition comprising ibuprofen salt is dissolved
and swallowed as a liquid dosage formulation. App. Br. 6. Appellant argues
that this is particularly so when ibuprofen is administered at high dosage and
maintains a fast, therapeutic effect. Id. at 6–7 (citing, e.g., Spec. 1, 3–4).
Appellant argues that the claimed composition completely masks the throat
irritating effect of ibuprofen at a dosage of 600 mg in solution. Id. at 8
(citing Moretto Decl. ¶ 12).
In support of this contention, Appellant points to the study described
in the Moretto Declaration. App. Br. 9 (citing Moretto Decl. ¶ 19).
According to Appellant, Dr. Moretto attests that a composition
corresponding to an embodiment taught by Gruber comprising ibuprofen and
sodium hydroxide at a ratio of 1 to 0.95 was compared to the claimed
composition, prepared by mixing 23.74 g of ibuprofen L-arginine salt
granulate (22.100 g of ibuprofen L-arginine salt and 1.64 g of sucrose) and
1.8560 g of sodium hydroxide so the molar ratio between Ibuprofen L-
arginine salt and sodium hydroxide was 1 to 0.80; both compositions were
then dissolved in water at a concentration of 6 mg/ml. App. Br. 10 (citing
Moretto Decl. ¶¶ 20, 21). Appellant states that the pH of the Gruber
composition was 6.7, whereas that of the claimed composition was 9.4. Id.
(citing Moretto Decl. ¶¶ 24, 25).
Appellant argues that Dr. Moretto states that test subjects (n = 2)
evaluated the Gruber solution as an “irritant” to the throat, noting that the
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unpleasant sensation remained for some time after ingestion. Id. (citing
Moretto Decl. ¶ 26). Dr. Moretto opines that these results demonstrate that
only the combination presently claimed is capable of preventing throat
irritation following the ingestion of an ibuprofen solution, because inhibition
of irritation effects occurs at pH above 9.0. Id. at 10–11 (citing Moretto
Decl. ¶ 27).
We do not find these results to be probative of unexpected or
surprising properties of Appellant’s claimed composition. “[W]hen
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). We
acknowledge that Gruber is the closest prior art to Appellant’s claimed
composition, but the embodiment selected for the study described in the
Moretto Declaration was not the closest embodiment compared to
Appellant’s composition. We have explained supra how Gruber teaches
solubilizing ibuprofen with a base, and then secondarily adding additional
base(s) of the type recited in claim 1. See, e.g., Gruber Examples 28 and 29.
Those embodiments are closer to what Appellant argues is the nature of the
claimed composition, yet such embodiments were not employed for
comparison in the Moretto study. Indeed, Appellant has not explained
which specific embodiment of Gruber is represented in ¶ 20 of the Moretto
Declaration, or explained why it should be considered the closest prior art
embodiment of the compositions taught by Gruber to the claimed
compositions.
Furthermore, and perhaps more importantly, it was generally well
known in the prior art that raising the pH solution of an ibuprofen solution
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was a way of masking the irritation-inducing effects of ibuprofen, although,
prior to Gruber, the use of alkali metal carbonates and phosphates was not
thought to be suitable for oral administration because of their high pH. See
Gruber ¶ 16:
U.S. Pat. No. 5,262,179 discloses non effervescent water soluble
compositions of water soluble ibuprofen salts in which the
unpleasant taste of the salt is masked by carbonates, mono
hydrogen phosphates and tribasic citrates in aqueous solution.…
The alkaline additives have the task of so strongly buffering an
ibuprofen salt solution that when drinking the pH does not drop
so far in the mouth through saliva that the ibuprofen, which has
a low solublitiy [sic] already at a pH value of 5–6, re-precipitates
and leads to irritation of the oral mucosa.

We consequently find that the results obtained in the Moretto
Declaration are not sufficient indicia of unexpected or surprising results to
overcome the Examiner’s prima facie conclusion that the claims are obvious
over the cited prior art. We consequently affirm the Examiner’s rejection of
claims 1–5, 7–11, 14–15, and 22.

DECISION
The Examiner’s rejection of claims 1–5, 7–11, 14–15, and 22 as
unpatentable 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
1–5, 7–11,
14–15, 22
103(a) Gruber

1–5, 7–11,
14–15, 22