FERRING B.V.

Patent Trials and Appeals Board

Oct 21, 2021

2021002948 (P.T.A.B. Oct. 21, 2021)

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.
15/643,727 07/07/2017 Alfred Chi-Yeh Liang 052209-0292 6561
22428 7590 10/21/2021
FOLEY & LARDNER LLP
3000 K STREET N.W.
SUITE 600
WASHINGTON, DC 20007-5109
EXAMINER
BROWE, DAVID
ART UNIT PAPER NUMBER
1617
NOTIFICATION DATE DELIVERY MODE
10/21/2021 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):
ipdocketing@foley.com
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
_________________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
_________________

Ex parte ALFRED CHI-YEH LIANG and
NIPUL GHANSHYAMBHAI PATEL
_________________

Appeal 2021-002948
Application 15/643,727
Technology Center 1600
_________________

Before JEFFREY N. FREDMAN, DEBORAH KATZ, and
DAVID COTTA, Administrative Patent Judges.

KATZ, Administrative Patent Judge.

DECISION ON APPEAL
Appellant1 seeks our review,2 under 35 U.S.C. § 134(a), of the
Examiner’s decision to reject claims 1–7, 9–15, 19, 20, and 26–34. We have
jurisdiction under 35 U.S.C. § 6(b). We AFFIRM.

1 We use the word “Appellant” as defined in 37 C.F.R. § 1.42. Appellant
identifies the real party in interest as Ferring B.V. (Appeal Br. 3.)
2 We consider the Final Office Action issued March 18, 2020 (“Final Act.”),
the Appeal Brief filed November 2, 2020 (“Appeal Br.”), the Examiner’s
Answer issued on February 17, 2021 (“Ans.”), the Reply Brief filed March
30, 2021 (“Reply Br.”) and the oral argument held on October 7, 2021, in
reaching our decision.
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Appellant’s Specification is directed to liquid formulations useful for
treating constipation or clearing the bowel prior to X-ray examination,
endoscopy or surgery. (See Spec. ¶¶ 3–4.)
Appellant’s claim 1 recites:
A liquid pharmaceutical formulation comprising:
picosulfate;
magnesium citrate;
a carboxylic acid chosen from malic acid, malonic acid,
and gluconic acid; and
an antioxidant chosen from ascorbic acid or a salt or ester
thereof, butylated hydroxyanisole, butylated hydroxytoluene,
histidine, D-mannose, propionic acid, potassium metabisulfite,
propyl gallate, sodium metabisulfite (Na2S2O5), sodium sulfite
(Na2SO3), sodium thiosulfate, sulfur dioxide, and α-tocopherol.

(Appeal Br. 22.) Appellant’s independent claim 32 is narrower,
encompassing only certain species of claim 1, and recites:
A liquid pharmaceutical formulation comprising
picosulfate, magnesium citrate, malic acid, and sodium
metabisulfite (Na2S2O5).

(Appeal Br. 25.)
The Examiner rejected claims 1 and 32, as well as dependent claims
2–7, 11–15, 19, 20, and 26–33, and 34 under 35 U.S.C. § 103 over Nam3
and Anonymous.4 (See Final Act. 7–11.) The Examiner also rejected

3 Korean Patent Application Pub. No. KR 1420315 81 B1; published July
17, 2014. Citations are to the English language equivalent, U.S. patent
application publication 2016/0324837 A1, published November 10, 2016.
(See Final Act. 9; see Appeal Br. 11, n. 2.)
4 ChEBI https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:114786;
last modified April 12, 2016
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dependent claims 9 and 10 under 35 U.S.C. § 103 as being unpatentable over
Nam, Anonymous, and Bottom.5 (See Final Act. 11–13.)
The Examiner further rejects claims 1–7, 9–15, 19, 20, and 26–34,
provisionally, under the ground of nonstatutory double patenting as being
unpatentable over claims 1–3, 8, 10, 12, 13, 17, 21–25, 28, 31, 33, 43, 47,
49, 56, and 64–66 of copending Application No. 15/238,408. (See Final
Act. 5–7.) Appellant does not appeal this rejection. (See Appeal Br. 8, n.1.)
Accordingly, the rejection is maintained.
Analysis
The Examiner finds that Nam discloses a pharmaceutical liquid
formulation for purgative pretreatments comprising sodium picosulfate,
magnesium citrate (formed from magnesium oxide and citric acid), malic
acid, and an additional stabilizing agent and/or preservative in water;
wherein the liquid formulation is chemically and physically stable. (See
Final Act. 9; see Nam Abstr., ¶¶ 3, 5) The Examiner finds further that
Anonymous discloses that sodium metabisulfite is a suitable stabilizing
agent, preservative, and antioxidant for pharmaceutical and food
preparations. (See Final Act. 9; see Anonymous.) The record supports the
Examiner’s findings.
The Examiner determines that one of ordinary skill in the art would
have been motivated to include sodium metabisulfite as an additional
stabilizing agent/preservative in the Nam liquid formulation, with a
reasonable expectation of success, because Anonymous teaches that it is
used for chemical and physical stability. (See Final Act. 9.)

5 U.S. Patent No. 5,010,069, issued April 23, 1991.
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Appellant argues that formulating picosulfate in a composition with
an antioxidant as recited in the pending claims results in a formulation with
improved stability, inhibiting or reducing the formation of specific
impurities and degradation products. (See Appeal Br. 10, citing Spec,
13:28–31.) Appellant cites to the Specification to support the argument that
the formation of these degradation products was unknown and, thus the
solution to this unknown problem was also unknown. (See Appeal Br. 10;
see Reply Br. 3.) The Specification states:
The inventors have found that liquid formulations comprising
picosulfate (e.g., sodium picosulfate) are not stable upon
storage and form degradation products. The inventors have
surprisingly found that the formation of degradation products
can be inhibited or reduced by including antioxidants in the
formulation solution.
(Spec. 13:28–31.) According to Appellant, one of ordinary skill in the art
would not have had a reason to modify the compositions of Nam and would
not have been motivated to do so by Anonymous. (See Appeal Br. 10.)
Specifically, Appellant argues that the compositions of Nam,
including malic acid, are already “physically and chemically stable when
stored,” even without an antioxidant. (Appeal Br. 11, citing Nam ¶¶ 12, 38,
39.) Appellant argues that Nam teaches using sodium benzoate as a
stabilizer or preservative in its picosulfate compositions. (See Appeal Br.
12, citing Nam ¶ 31.) Appellant argues further that Nam teaches that malic
acid alone is sufficient to address stability issues and that the Examiner has
not provided a reason why one of ordinary skill in the art would have
departed from the teachings of Nam to use a different excipient. (See
Appeal Br. 12, citing Nam ¶ 5, 39, Table 4 (Example 4); see also Appeal Br.
14–15; see Reply Br. 3–4.) According to Appellant, nothing in Anonymous,
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or in the combination of Nam and Anonymous, could have suggested that
adding sodium metabisulfite would further improve the stability of Nam's
picosulfate composition or have provided a reasonable expectation of
success in that regard. (See Appeal Br. 13.)
We are not persuaded by these arguments because Nam teaches that in
addition to precipitation in compositions with magnesium citrate, “there
arises a problem such that sodium picosulfate becomes unstable.” (Nam
¶ 5.) Thus, the problem of instability was known to those of ordinary skill in
the art before Appellant’s filing date. In addition, Nam teaches adding
several different stabilizers to compositions of sodium picosulfate,
magnesium oxide, citric acid, in addition to malic acid. Nam teaches that
compositions of the invention can include additional ingredients, including a
stabilizer or a preservative. (See Nam ¶¶ 17–18; see Ans. 5.) Nam provides
Example 1, which includes a different preservative, disodium edetate
hydrate (“EDTA”), that was used “as a stabilizer” in addition to malic acid.
(Nam ¶ 31; see Ans. 4.)
Because Nam teaches that additional stabilizers and preservatives
could be used, we are persuaded that those of ordinary skill in the art would
have been motivated to add sodium bisulfite in addition to malic acid to a
liquid pharmaceutical composition of picosulfate as recited in claim 1. The
Examiner explains that the rejection is not based on substituting any of the
stabilizers or preservatives taught in Nam with sodium metabisulfite, but
rather that one of ordinary skill in the art would have been motivated to use
sodium metabisulfite as the stabilizer or preservative taught in paragraph 18
of Nam, if further improved stability was needed. (See Ans. 6.)
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We are persuaded by the Examiner’s findings. Although Appellant
argues that Example 4 of Nam reports that formulations including malic acid
without additional stabilizers were stable over 24 months (exhibiting
degradation of sodium picosulfate of 2.0% or less) Appellant fails to
persuade us that further stabilization would not have been desirable to those
in the art. (See Appeal Br. 12; see Reply Br. 4.) Appellant does not direct
us to evidence that there is an upper limit to stability, beyond which those in
the art do not try to achieve.
Appellant argues further that the Examiner erred in finding that
Anonymous teaches sodium metabisulfite as a preservative for
pharmaceuticals because it teaches being a preservative only for food. (See
Appeal Br. 13–14; see Reply Br. 5.) Although we agree with Appellant that
the Examiner overstates the express teachings of Anonymous, we agree with
the Examiner that one of ordinary skill in the art would have understood
from Anonymous that sodium metabisulfite is useful as a stabilizer for
human consumption. (See Ans. 7.) Because Appellant’s claimed
pharmaceutical formulation is intended for consumption, we are persuaded
that it would have been obvious to include sodium metabisulfite, absent
evidence that it would behave differently in pharmaceutical formulations
than in food. (See Spec. 2:19–21 (“To overcome the disadvantages
described above, it would be desirable to be able to supply formulations
containing picosulfate in liquid form, ready for consumption by the
patient.”).)
Appellant argues that the stability problems of picosulfate
compositions were not recognized before the date of Appellant’s
Specification was filed, and that, therefore, the claimed formulations exhibit
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stability properties that could not have been predicted or expected from the
cited combination of references. (See Appeal Br. 16; see Reply Br. 7.)
According to Appellant, the inventors “unexpectedly found that liquid
picosulfate formulations may exhibit, after a period of storage, the formation
of impurities/degradation products not previously addressed, e.g., the
Picosulfate Benzyl Alcohol, Compound RRT 1.35, and Compound RRT
1.94 impurities/degradation products discussed in the present specification.”
(Appeal Br. 10.)
This argument is unpersuasive because Nam expressly teaches that
compositions including sodium picosulfate become unstable and
Anonymous demonstrates that the preservative sodium bisulfite was known
at the time. (See Nam ¶ 5.) We agree with the Examiner’s finding that one
of ordinary skill would have expected a composition to become more stable
after including a stabilizer. (See Ans. 8.) Appellant does not direct us to
evidence that the claimed composition solves the problem of degradation to
the identified impurities (Compound RRT 1.35, and Compound RRT 1.94)
other than by acting as a generalized preservative. It is not clear how the
inventor’s alleged discovery of the nature of specific degradation products
renders the use of sodium bisulfite unexpected when it was known to be a
preservative. We agree with the Examiner that
[a]nyone of ordinary skill in the art would immediately
understand that a “stabilizer” makes the composition more
stable by preventing or attenuating the formation of degradation
products, including those that result from the degradation of the
active principle. Indeed, this is the chief function of any
“stabilizer” in the context of the formulation arts. As anyone of
ordinary skill in the art has long recognized for many decades if
not centuries, all pharmaceutical compositions are susceptible
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to degradation over time, and its universally well known that
this involves the formation of degradation compounds or
products, which sometimes lead to foul discoloration and/or
odors.
(Ans. 8.)
Appellant argues that there is no teaching or suggestion in
Anonymous, or in the combination of Nam and Anonymous, that sodium
metabisulfite would be suitable for use in a composition according to Nam.
(Appeal Br. 14.) We are not persuaded by this argument because, as noted
by the Supreme Court, “[i]n many fields it may be that there is little
discussion of obvious techniques or combinations, and it often may be the
case that market demand, rather than scientific literature, will drive design
trends.” KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 419 (2007).
Anonymous shows that sodium metabisulfite was a known preservative for
human consumption and Nam teaches that other stabilizers and
preservatives, without limitation, could be used in solutions of sodium
picosulfate. (See Nam ¶¶ 17, 18.) Thus, we are persuaded that it would
have been obvious to include sodium metabisulfite in a composition as
taught in Nam.
Appellant argues further that the claimed composition is patentable
because it was unexpectedly stable, citing to the results shown in Tables 13
and 14 of the Specification. (See Appeal Br. 15–16.) Tables 13 and 14
report that Formulation J, which includes malic acid, but not an antioxidant
as recited in the claims, is less stable than Formulations 6–10, which include
both malic acid and an antioxidant recited in the claims. (See Appeal Br.
16.)
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We are not persuaded that these results would have been unexpected
because Appellant does not direct us to evidence, such as testimony
explaining how one of ordinary skill in the art would have interpreted the
results. Appellant merely cites to the results showing that the claimed
formulation “exhibit stability . . . as compared to formulations prepared
without an antioxidant selected from the list recited in the claims . . . .”
(Appeal Br. 15–16; see also Reply Br 7.) According to Appellant, it was not
previously realized that liquid picosulfate formulations were unstable
(which, as discussed above, is contradicted by the teachings of Nam), but
Appellant does not direct us to evidence that the solution to this problem
would have been unexpected, when sodium bisulfite was a known
preservative. See In re DeBlauwe, 736 F.2d 699, 705 (Fed. Cir. 1984) (“It is
well settled that unexpected results must be established by factual evidence.
Mere argument or conclusory statements in the specification does not
suffice.”).
Appellant argues that the decisions in In re Sponnoble, 405 F.2d 578,
585–86 (CCPA 1969), and In re Omeprazole Patent Litigation, 536 F.3d
1361 (Fed. Cir. 2008), instruct that an invention stemming from the
discovery of a previously unknown problem can be non-obvious even if the
claimed solution appears obvious in hindsight. (See Appeal Br. 10, 12.) We
are not persuaded that the facts of these cases indicate Appellant’s claimed
composition would have been nonobvious.
In Sponnoble, the problem solved by the inventor (transmission of
moisture into the lower mixing compartment) was known in the art, even if
the reason for this problem (passage of moisture through, rather than around,
the plug) was not known. See Sponnoble, 405 F.2d at 585–86. The inventor
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in Sponnoble contributed to the art by proposing a solution that addressed
the specific problem (a non-porous plug) that would not have occurred to
others at the time. In contrast, Appellant proposes a solution to the problem
of degradation with a preservative known in the art. Appellant fails to
explain how this solution is specific to the degradation products reportedly
identified by the inventors or would not have been obvious given it was
known from the teachings of Nam that sodium picosulfate compositions
were unstable.
Similarly, in Omeprazole the court held that the claimed drugs would
not have been obvious because “[e]ven if a person of skill in the art would
have recognized that there would be a negative interaction between the
enteric coating and the drug core, the district court found that it would not
have been obvious to try applying a water-soluble subcoating as a means of
solving that problem.” See Omeprazole, 536 F.3d at 1380–81. In contrast,
we agree with the Examiner that the solution identified by the inventors
would have been obvious to others of ordinary skill in the art given the
knowledge of the instability of picosulfate compositions and that sodium
metabisulfite was a preservative. We are not persuaded that any solution to
an unrecognized problem is necessarily nonobvious under the holding of
Omeprazole.
Appellant fails to persuade us that the Examiner erred in rejecting
claim 1.
Claims 5, 7, and 32–34
Claims 5, 7, and 32–34 are limited to a liquid pharmaceutical
formulation wherein the antioxidant is sodium metabisulfite or potassium
metabisulfite. (See Appeal Br. 22, 25.) Appellant points to the results
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presented in Table 14 of the Specification to argue that these two
compounds exhibited greater stability than a formulation with ascorbic acid
or without antioxidant. (See Appeal Br. 17.)
For the reasons discussed above in regard to claim 1, we are not
persuaded that the formulations of claims 5, 7, or 32–34 would have been
nonobvious to one of ordinary skill in the art at the time. We note that
Appellant argues that the results reported in Table 14 demonstrate that
formulations with sodium metabisulfite or potassium metabisulfite produce
greater stability over formulations with ascorbic acid, which is also recited
in claim 1. (See id.) Appellant fails to explain what qualifies some
members of the Markush group of claim 1 as producing “particularly good”
results, while other members produce merely “unexpected” results. (Id.)
For the reasons discussed above, and in the absence of further evidence of
how those of ordinary skill in the art would have interpreted these results,
we are not persuaded that they indicate the claimed formulations would have
been nonobvious.
Claims 29–31
Claims 29–31 recite specific stability properties for the claimed
formulations when stored for one year at about 25o C and about 69% relative
humidity. (See Appeal Br. 24–25.) Appellant argues that these claims are
separately patentable because the cited references do not suggest or provide
a reasonable expectation of success for formulations that exhibit these
properties. (See Appeal Br. 17–18.)
We are persuaded that the formulations of these claims would have
been obvious for the reasons discussed above in regard to claim 1. We are
persuaded by the Examiner’s findings and reasoning that it would have been
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obvious to include sodium metabisulfite the formulation of Nam, for the
reasons discussed above. Such formulations would inherently have the
claimed properties. Appellant argues that it is improper to use inherency as
the basis for finding claimed subject matter obvious (see Appeal Br. 18–19),
but the inherency of the resulting formulation is not the reason the
formulation of claim 1 would have been obvious. The mere recitation of
inherent properties of an obvious formulation does not render the
formulation less obvious. See, e.g., PAR Pharm., Inc. v. TWI Pharm., Inc.,
773 F.3d 1186, 1194--95 (Fed. Cir. 2014) (“We have recognized that
inherency may supply a missing claim limitation in an obviousness
analysis.”).
Claims 9 and 10
Claims 9 and 10 depend on the claim 1 and recite liquid
pharmaceutical formulations with defined ranges of antioxidant
concentration. (See Appeal Br. 23.)
The Examiner cites Bottom for its teaching of a pharmaceutical liquid
formulation at pH 3–5 that comprises 0.005 M sodium metabisulfite, which
is within the ranges recited in both claims 9 and 10, as an antioxidant, and
wherein the formulation is stable and does not significantly discolor due to
decomposition for extended periods of time. (See Final Act. 12, citing
Bottom abstract; 2:42–47, Example 1.)
Appellant argues that Bottom does not teach using sodium
metabisulfite in formulations of picosulfate, but only in formulations of 5-
aminosalicyclic acid. (See Appeal Br. 19–20.) Appellant argues further that
the focus of Bottom is not the use of sodium metabisulfite as an antioxidant,
but rather the absence of buffers such as citrate or acetate buffer. (See id.)
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According to Appellant, Bottom “takes a completely different approach to
improving stability of a completely different active agent.” (Appeal Br. 20.)
We are not persuaded by Appellant’s arguments because Bottom was
cited merely for teaching that it was known to use sodium metabisulfite at a
concentration within the scope of Appellant’s claims in a liquid formulation.
(See Ans. 12–13.) For the reasons discussed above, we are persuaded that
one of ordinary skill in the art would have combined the teachings of Nam
and Anonymous to arrive at the other elements of Appellant’s claimed
formulations.
Conclusion
Upon consideration of the record and for the reasons given, we affirm
the Examiner’s rejections.
In summary:
Claims
Rejected
35 U.S.C.
§
Basis/Reference(s) Affirmed Reversed
1–7, 11–15,
19, 20, 26–
34
103 Nam, Anonymous 1–7, 11–15,
19, 20, 26–
34

9, 10 103 Nam, Anonymous,
Bottom
9, 10
Overall
Outcome
1–7, 9–15,
19, 20, 26–
34

No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136.

AFFIRMED