GRÜNENTHAL GMBH

Patent Trials and Appeals Board

Mar 18, 2021

2021000498 (P.T.A.B. Mar. 18, 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.
15/823,918 11/28/2017 KLAUS WENING 107101-230 (200) KGB 5988
27384 7590 03/18/2021
Briscoe, Kurt G.
Norris McLaughlin, PA
7 Times Square, 21st Floor
New York, NY 10036-6524
EXAMINER
ARNOLD, ERNST V
ART UNIT PAPER NUMBER
1613
NOTIFICATION DATE DELIVERY MODE
03/18/2021 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):
jarcher@norris-law.com
nmanfredi@norris-law.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
________________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
________________

Ex parte KLAUS WENING, ANJA GEIßLER,
JANA DENKER, and LUTZ BARNSCHEID1
________________

Appeal 2021-000498
Application 15/823,918
Technology Center 1600
________________

Before ULRIKE W. JENKS, JOHN G. NEW, and RYAN H. FLAX,
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 identifies Grünenthal GmbH as the real
party-in-interest. 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 95–101 as unpatentable under
35 U.S.C. §103 being obvious over Arkenau-Maric et al. (WO 2008107149,
Mar. 7, 2007 (the Examiner relies upon US 2009/0004267 A1, January 1,
2009) as the English translation) (“Arkenau-Maric”), J. Fitzpatrick, The
Influence of Superdisintegrants on Immediate Release, 23(6)
PHARMACEUTICAL TECHNOL. EUROPE (2011), available at:
https://www.pharmtech.com/view/ influence-superdisintegrants-immediate-
release (last visited February 19, 2021) (“Fitzpatrick”), D.J. Heal et al.,
Amphetamine, Past and Present: A Pharmacological and Clinical
Perspective, 27(6) J. PSYCHOPHARMACOL. 479–496 (2013) (“Heal”), S.
Lefnaoui et al., Synthesis and Evaluation of the Structural and
Physicochemical Properties of Carboxymethyl Pregelatinized Starch as a
Pharmaceutical Excipient, 23 SAUDI PHARM. J. 698–711 (2015)
(“Lefnaoui”), J. Lopez-Solis et al., Effect of Disintegrants with Different
Hygroscopicity on Dissolution of Norfloxacin/Pharmatose DCL 11 Tablets,
216 INT. J. PHARMS. 127–135 (2001) (“Lopez-Solis”), and V. Buhler,
POLYVINYLPYRROLIDONE EXCIPIENTS FOR PHARMACEUTICALS: POVIDONE,
CROSPOVIDONE AND COPOVIDINE, 149–164 (Springer 2010) (“Buhler”).
Claims 95–101 also stand provisionally rejected under the
nonstatutory doctrine of obviousness-type double patenting as being
unpatentable over claims 29–32, 34, 35, 43, 44, 46–53, 58, and 59 of
copending US Appl. Ser. No. 16/116,282 (the “’282 application”).
Claims 95–101 also stand provisionally rejected under the
nonstatutory doctrine of obviousness-type double patenting as being
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unpatentable over claims 11–25 of copending US Appl. Ser. No. 16/217,839
(the “’839 application”).
Claims 95–101 stand further provisionally rejected under the
nonstatutory doctrine of obviousness-type double patenting as being
unpatentable over claims 2–4, 6–9, 17, 20, 26–30, 36, 40, 44, 68–73, and
75–79 of copending US Appl. Ser. No. 15/260,643 (the “’643 application”).
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 tamper-resistant
pharmaceutical dosage form comprising a multitude of particles comprising
a pharmacologically active compound, a polyalkylene oxide, and a
disintegrant. Spec. Abstr.

REPRESENTATIVE CLAIM
Independent claim 95 is representative of the claims on appeal
and recites:
95. A tamper-resistant pharmaceutical dosage form
comprising a multitude of particles each of which particles
comprises a homogeneous mixture of a pharmacologically
active compound, a polyalkylene oxide, and a disintegrant;

wherein the pharmacologically active compound is
selected from the group consisting of amphetamine,
dexamphetamine, and the physiologically acceptable salts
thereof;

wherein the disintegrant is pregelatinized starch;

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wherein the polyalkylene oxide is polyethylene oxide;

wherein the content of the disintegrant is more than 5.0
wt.-%, based on a total weight of the pharmaceutical
dosage form and/or based on a total weight of the particles;

wherein the content of the polyalkylene oxide is at least 25
wt.-%, based on the total weight of the pharmaceutical
dosage form and/or based on the total weight of the
particles;

wherein the particles exhibit a breaking strength of at least
300 N; and

wherein the pharmaceutical dosage form simultaneously
provides:

(a) a dissolution release profile such that under in vitro
conditions in 600 ml 0.1 M HCl (pH 1) at 75 rpm
after 30 min at least 80 wt.-% of the
pharmacologically active ingredient that was
originally contained in the dosage form have been
released; and

(b) a resistance to solvent extraction as determined by
a process comprising:

(i) dispensing the particles in 5 ml of boiling
water;

(ii) boiling the particles in the boiling water for 5
minutes to obtain a liquid;

(iii) attempting to draw a quantity of the liquid up
into a syringe having needle 21G equipped
with a cigarette filter; and

(iv) determining by high-performance liquid
chromatography the amount of the
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pharmacologically active ingredient
contained in any quantity of liquid that could
be drawn up into the syringe, wherein said
any quantity of liquid that could be drawn up
into the syringe contains less than 10 wt.% of
the pharmacologically active compound
originally contained in the dosage form.

App. Br. 26–27.

ISSUES AND ANALYSES
We adopt the Examiner’s findings, reasoning, and conclusion that the
claims on appeal are prima facie obvious over the combined cited prior art.
We address the arguments raised by Appellant below.

Issue 1

Appellant argues that the Examiner erred because the combined cited
prior art neither teaches nor suggests the limitation of claim 95 reciting “a
dissolution release profile such that under in vitro conditions … wherein said
any quantity of liquid that could be drawn up into the syringe contains less
than 10 wt% of the pharmacologically active compound originally contained
in the dosage form.” App. Br. 8.

Analysis
The Examiner finds that Arkenau-Maric teaches a multiparticulate
pharmaceutical form, in the form of a tablet or capsule, which impedes
abuse (thus, is tamper resistant), including at least one active ingredient with
the potential for abuse (A), at least one synthetic or natural polymer (C),
optionally at least one natural, semi-synthetic, or synthetic wax (D), at least
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one disintegrant (E), and optionally one or more additional physiologically
tolerable excipients (B), wherein the individual particles of the
pharmaceutical form have a breaking strength of at least 500 N and an active
ingredient release of at least 75% after 45 minutes, measured in the paddle
mixer under in vitro conditions with 80% being released after 30 minutes.
Final Act. 4–5 (citing Arkenau-Maric Abstr., ¶¶ 17, 166, 170, 172, claims 1–
12, 20).
The Examiner finds that Arkenau-Maric teaches that the active
ingredient is mixed in the matrix of (C), which reads on a homogenous
mixture. Id. at 5 (citing Arkenau-Maric claim 23). The Examiner finds that
Arkenau-Maric teaches that active ingredient (A) can be a stimulant such as
amphetamines, methylphenidate, or pseudoephedrine. Id. (citing Arkenau-
Maric claim 17, ¶ 24). The Examiner also finds that Arkenau-Maric teaches
that polymer (C) can be polyalkylene oxides with a molecular weight of at
least 500,000 or from 1,000,000 to 15,000,000 in an amount of 35–99.9
wt%. Id. (citing Arkenau-Maric claims 1–6, ¶ 30).
The Examiner finds that Arkenau-Maric further teaches that the
dosage form contains from 0.5–25 wt%, 0.1–15 wt% and preferably 1–10
wt% of a disintegrant like polysaccharides such as croscarmellose, modified
maize starch, sodium carboxymethylcellulose, sodium carboxymethyl starch,
as well as the polyvinylpryrrolidone crospovidone. Final Act. 5 (citing
Arkenau-Maric ¶ 31, claims 1–12). The Examiner further finds that
Arkenau-Maric teaches immediate release dosage forms. Final Act. 5 (citing
Arkenau-Maric ¶ 21).
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The Examiner finds that Fitzpatrick teaches that an artisan would
choose an optimal disintegrant. Final Act. 5. Specifically, the Examiner
finds that Fitzpatrick teaches:
It is important to consider the impact of the superdisintegrant
with respect to the performance of the final dosage form. As
drug dissolution is essential for absorption by the body,
formulators no longer select disintegrants based on the lowest
disintegration time because it is important to also consider the
effect of the superdisintegrant on dissolution. Additionally, the
ionic nature of both the API and the superdisintegrants must also
be considered. Anionic superdisintegrants, such as
croscarmellose sodium and sodium starch glycolate, can interact
with cationic APIs and retard dissolution.

Id. at 5–6 (quoting Fitzpatrick 1). The Examiner concludes that a skilled
artisan in the pharmaceutical arts would have understood that the choice of
disintegrant impacts dissolution performance. Id. at 6. The Examiner also
finds that Fitzpatrick also teaches:
Crospovidone possesses unique pyrrolidone chemistry and a
highly porous particle morphology that results in high surface
area. The high surface area combined with unique chemistry
results in high-interfacial activity that serves to enhance the
dissolution of poorly soluble drugs in a way that is not possible
with other disintegrant technologies.

Id. (citing Fitzpatrick 1).
The Examiner finds that Heal teaches that amphetamines are
commonly administered as a sulfate salt that has two optically active forms:
the dextro-, or d-, and levo-, or l-. Final Act. 6 (citing Heal, 481, Table 1,
479). The Examiner concludes that Heal thus renders obvious
dexamphetamine, because amphetamine naturally includes dexamphetamine.
Id.
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The Examiner finds that Buhler teaches that crospovidone and
carboxymethyl starch (4%), in equal amounts, have similar disintegration
rates. Id. (citing Buhler, Table 138).
The Examiner finds that Lefnaoui teaches that modified maize starch
is pregelatinized maize starch and has advantages such as cold water
solubility, high viscosity, and moisture sorption and swelling, with excellent
disintegration/dissolution properties. Final Act. 7 (citing Lefnaoui 699).
The Examiner finds that Lopez-Solis teaches the differences between
the disintegrants Starch 1500 (pregelatinized starch) and crosslinked
polyvinylprryolidone. Final Act. 7 (citing Lopez-Solis Abstr., 129, 2.1).
The Examiner finds that Lopez-Solis also teaches that Starch 1500 can form
a swollen matrix that restricts dissolution process after about 12%
dissolution, and can form a gelatinous mass. Id. (citing Lopez-Solis, 131).
The Examiner further finds that Lopez-Solis teaches that, in contrast,
crosslinked polyvinylpyrrolidone has little tendency to gel and increases
dissolution, opposed to Starch 1500. Id. (citing Lopez-Solis 133, 134).
The Examiner concludes that it would have been obvious to a person
of ordinary skill in the art to combine the compositions of Arkenau-Maric
with a pregelatinized starch disintegrant, as taught by both Lopez-Solis and
Lefnaoui, and a stimulant, including dexamphetamine sulfate, as taught by
of Heal. Final Act. 9. The Examiner reasons that the resulting composition
would have an increased resistance to solvent extraction, as taught by
Fitzpatrick, exhibiting simultaneous dissolution of at least 80% after 30 min
and increased resistance against solvent, as recited in claim 95. Id.
The Examiner further concludes that a skilled artisan would have been
motivated to so combine the references, because doing so follows the
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guidelines set forth by Arkenau-Maric. Final Act. 9. The Examiner notes
that, with regard to pregelatinized starch, Arkenau-Maric teaches using a
“modified maize starch.” Id. (citing Arkenau-Maric claim 13). The
Examiner finds that a person of ordinary skill in the art would understand
that a “modified maize starch” is pregelatinized maize starch, which possess
the advantages of cold water solubility, high viscosity, and moisture sorption
and swelling, with excellent disintegration/dissolution properties. Id. at 9–
10. The Examiner also reasons that a person of ordinary skill in the art
would understand, from the teachings of Lopez-Solis and Lefnaoui, that a
pregelatinized starch, such as the conventional and commercially-available
Starch 1500, has functional properties dependent upon the amount employed
in the dosage form: viz., that a large quantity of Starch 1500 can gel, and
thus restrict dissolution. Id. at 10. The Examiner concludes that an
ordinarily-skilled artisan would therefore not only have been motivated to
use pregelatinized maize starch for its desirable properties but would also
have had a reasonable expectation of success in using pregelatinized starch
with the dosage forms taught by Arkenau-Maric. Id.
Appellant contends that the combined cited prior art neither teaches
nor suggests the limitation of independent claim 95 reciting:
[W]herein the pharmaceutical dosage form simultaneously provides:

(a) a dissolution release profile such that under in vitro
conditions in 600 ml 0.1 M HCl (pH 1) at 75 rpm after 30
min at least 80 wt.-% of the pharmacologically active
ingredient that was originally contained in the dosage
form have been released; and

(b) a resistance to solvent extraction as determined by
a process comprising:
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…

wherein said any quantity of liquid that could be drawn up into
the syringe contains less than 10 wt.% of the pharmacologically
active compound originally contained in the dosage form.

App. Br. 8. According to Appellant, the Examiner argues that the functional
elements of the pending claims are inherently disclosed in the prior art. Id.
(citing Final Act. 10).
Appellant argues first that a rejection for inherent anticipation (which
Appellant defines as a rejection for inherency in view of a single prior art
reference) is only proper where the composition is identical to a composition
disclosed in the single reference. App. Br. 8. Appellant contends that, in the
appeal presently before us, the Examiner has acknowledged that the
composition disclosed in Arkenau-Maric, is not identical to the claimed
composition. Id. at 8–9. Specifically, Appellant argues that Arkenau-Maric
does not teach the use of the claimed disintegrating agent (pregelatinized
starch) and dexamphetamine. Id. at 9 (citing Final Act. 12). Appellant
points out that, for this reason, the outstanding rejection is a § 103 rejection,
not a § 102 rejection. Id. Appellant therefore approaches the Examiner’s
rejection as an inherent obviousness rejection, i.e., the functional limitations
are inherently disclosed in Arkenau-Maric together with the secondary
references, Lopez-Solis, Lefnaoui, and Heal. Id.
Appellant argues that the Examiner has failed to establish that “the
limitation at issue necessarily must be present, or the natural result of the
combination of elements explicitly disclosed by the prior art.” App. Br. 9
(quoting Par Pharm., Inc. v. TWI Pharms., Inc., 773 F.3d 1186, 1196 (Fed.
Cir. 2014)). Specifically, argues Appellant, the Examiner has not provided
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any factual basis to conclude that the recited claim limitations are
necessarily present in the prior art. Id.
Appellant points to the Examiner’s finding that:
The ordinary artisan fully understands that starch disintegrants
and crospovidone can both function with similar disintegration
times and dissolution times when the same low amount is
employed, as taught by Buhler, but the amount of pregelatinized
starch disintegrant is a result effective variable where larger
amounts of pregelatinized starch can gel and decrease dissolution
of the active agent thus providing resistance to solvent extraction
under the conditions instantly claimed. This is entirely obvious
given that the active agent is entrapped in the gel which would
resist passage through a needles and thus would prevent any
liquid to be drawn into the syringe resistance solvent extraction
method of instant claim 95.

App. Br. 9–10 (quoting Final Act. 10). Appellant contends that this
rationale does not support the conclusion that both the dissolution and
resistance to extraction properties recited in the pending claims are
necessarily present in the prior art. Id. at 10. According to Appellant, the
Examiner finds that a small amount of pregelatinized starch would show
good dissolution properties while a larger amount of pregelatinized starch
would show good solvent extraction properties. Id. But, Appellant argues,
the Examiner does not find that the same amount of pregelatinized starch
would exhibit both properties simultaneously, let alone the specific
dissolution properties recited in the pending claim or resistance to solvent
extraction, measured as recited in the pending claim. Id. Appellant
contends that, whereas inherency can be used to supply a missing claim
limitation, it is an error to utilize inherency without satisfying the requisite
evidentiary showings. Id.
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We do not find Appellant’s arguments persuasive. The limitations in
question relate to how the composition performs under certain prescribed
conditions, i.e., they are functional limitations.
[W]here the Patent Office has reason to believe that a functional
limitation asserted to be critical for establishing novelty in the
claimed subject matter may, in fact, be an inherent characteristic
of the prior art, it possesses the authority to require the applicant
to prove that the subject matter shown to be in the prior art does
not possess the characteristic relied on.

In re Best, 562 F.2d 1252, 1254–55 (C.C.P.A. 1977) (quoting In re
Swinehart, 439 F.2d 210, 212–13 (C.C.P.A. 1971)). Furthermore,
Where, as here, the claimed and prior art products are identical
or substantially identical, or are produced by identical or
substantially identical processes, the PTO can require an
applicant to prove that the prior art products do not necessarily
or inherently possess the characteristics of his claimed product.
Whether the rejection is based on ‘inherency’ under 35 U.S.C.
§ 102, on ‘prima facie obviousness’ under 35 U.S.C. § 103,
jointly or alternatively, the burden of proof is the same, and its
fairness is evidenced by the PTO’s inability to manufacture
products or to obtain and compare prior art products.

Best, 562 F.2d at 1255 (citation omitted).
We disagree with Appellant and find that the Examiner’s rejection is
properly based on inherency under § 103 and our reviewing court’s
precedent. Here, the Examiner finds (and Appellant does not contest) that
the combined prior art, and particularly Arkenau-Maric and Lefnaoui,
teaches or suggests all of the structural limitations of the claimed
composition, the burden of showing that the combined teachings of the cited
prior art would not inherently possess the claimed functional characteristics
falls upon Appellant. Appellant has adduced no evidence of record to show
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that Examiner’s findings that the composition arrived at by combining the
teachings of the cited prior art would not possess the functional properties
recited in the limitations at issue. We are consequently not persuaded by
Appellant’s arguments with respect to this issue.

Issue 2
Appellant argues that, because the Examiner has failed to establish a
motivation or reason to combine the teachings of the cited prior art
references, the Examiner has impermissibly relied upon hindsight analysis.
App. Br. 11.

Analysis
Appellant notes that the Examiner finds that Arkenau-Maric discloses
“modified maize starch,” and that a skilled artisan would understand that
Lefnaoui teaches that modified maize starch is pregelatinized maize starch,
with certain desirable properties. App. Br. 11 (citing Final Act. 9–10).
Appellant contends that, although Arkenau-Maric broadly teaches modified
maize starch as a disintegrant, this does not mean that the reference provides
guidance to utilize a disintegrant that is not specifically taught, i.e.,
pregelatinized starch. Id. at 11–12. Appellant argues that this is true even
though pregelatinized starch is taught as having desirable properties in the
other cited references. Id. at 12. According to Appellant, the fact that a
claimed species or subgenus is encompassed by a prior art genus is not
sufficient by itself to establish a prima facie case of obviousness. Id. (citing
In re Baird, 16 F.3d 380, 382 (Fed. Cir. 1994); In re Jones, 958 F.2d 347,
350 (Fed. Cir. 1992)).
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Appellant therefore argues that the Examiner’s substitution of the
“modified maize starch” of Arkenau-Maric with Lefnaoui’s pregelatinized
starch is impermissible hindsight, because Arkenau-Maric does not
expressly teach pregelatinized starch. App. Br. 12 (citing Personal Web
Techs., LLC v. Apple, Inc., 848 F.3d 987, 993–94 (Fed. Cir. 2017)).
Furthermore, argues Appellant, the Examiner overlooks the teachings
of the references that, when read as a whole, teach that the ability of
pregelatinized starch to function as a disintegrant in pharmaceutical dosage
forms depends upon: (1) the pharmaceutical active agent; (2) the amount of
the starch used; and (3) the precise starch used. App. Br. 12. Specifically,
Appellant contends, the Examiner overlooks: (1) Lopez-Solis’ teaching that
the ability for starch to function as a disintegrant is dependent upon the
water solubility properties of the major components of the dosage form,
including drugs with different solubilities; (2) Lopez-Solis’ teaching that the
ability of starch to function as a disintegrant is dependent upon the amount
used and, in particular, that “if the quantity of Starch 1500 is big enough, the
matrix does not disintegrate”; (3) the teaching of Lopez-Solis that the
identity of the starch matters; and (4) the teaching in Lefnaoui that the
identity of the starch matters and, specifically, that pregelatinized starch
tablets showed higher friability and less hardness compared with
carboxymethyl pregelatinized starch. Id. at 12–13 (citing Lopez-Solis 128,
131, 133; Lefnaoui 707–708).
Furthermore, Appellant argues, Lefnaoui actually teaches that
“[p]regelatinized maize starch is physically modified maize starch,” whereas
an artisan of ordinary skill would have understood that physical modification
is only one method of modifying maize starch; chemical and enzymatic
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methods are also well-known strategies in the art for modifying maize
starch. App. Br. 13–14 (citing, e.g., Wikipedia, Modified starch, available
at: https://en.wikipedia.org/wiki/Modified_starch (last visited February 24,
2021)). Appellant therefore contends that the Examiner’s finding that a
skilled artisan would have selected pregelatinized starch from the various
modified starches available in the prior art constitutes impermissible
hindsight. Id. at 14.
The Examiner responds that a disintegrant functions as a disintegrant
regardless of the active pharmaceutical species. Ans. 6. The Examiner
further notes that Appellant also ignores the specific teaching in Lefnaoui
about the highly desirable properties of pregelatinized starch, viz., “cold
water solubility, high viscosity, and moisture sorption and swelling.… It
provides uniform filling of dies to ensure correct dosage, and has excellent
disintegration/dissolution properties.” Id. (quoting Lefnaoui 699). The
Examiner therefore finds that an ordinary artisan would have been motivated
to select pregelatinized maize starch as the modified maize starch of
Arkenau-Maric, so as to obtain these advantageous properties. Id.
We are not persuaded by Appellant’s arguments. Arkenau-Maric
teaches:
Physiologically acceptable disintegra[n]ts agents, such as are
used for the preparation of pharmaceutical dosage forms can be
used as disintegra[n]ts (E). Preferred for use as disintegrat (E) is
at least one disintegra[n]t selected from the group consisting of
crosslinked sodium carboxymethyl cellulose
(crossca[r]mellose), modified maize starch, sodium
carboxymethyl starch, crosslinked polyvinylpyrrolidone
(crosspovidone). The dosage forms according to the invention
preferably contain from 0.5 to 25% by weight, more preferably
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from 1 to 10% by weight, based on the total weight of the dosage
form, of at least one disintegrating agent (E).

Arkenau-Maric ¶ 31 (emphasis added); see also claim 13. Arkenau-Maric
thus expressly teaches that a modified maize starch is one of a limited list of
preferred disintegrants. It therefore follows that a person of ordinary skill in
the art would have looked to, inter alia, acceptable forms of modified maize
starch to incorporate into the compositions of Arkenau-Maric.
Lefnaoui teaches, generally that:
Starches are mainly used in oral solid dosage forms as fillers,
binders or disintegrants. However they have some limitation
properties. To improve their properties such as flowability,
gelatinizing temperature, gel viscosity, hydrophilicity, or
swelling characteristic, starches have been modified.
Modifications including physical, chemical and genetic
modification were introduced as matrices forming excipients for
oral sustained-release dosage forms.

Lefnaoui 699 (internal references omitted). Lefnaoui then teaches, in the
immediately succeeding paragraph:
Pregelatinized maize starch is physically modified maize starch
with main advantages such as cold water solubility, high
viscosity, and moisture sorption and swelling. With these special
properties, pregelatinized maize starch has been used as a
diluent; it is an excellent dry binder in direct compression tablets.
It provides uniform filling of dies to ensure correct dosage, and
has excellent disintegration/dissolution properties.

Id. (internal references omitted). Lefnaoui thus teaches that it was well
known in the art that modified starches could be improved by modification
and that pregelatinized, and therefore modified, maize starch provided
excellent properties as a disintegrant.
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We consequently agree with the Examiner that a person of ordinary
skill in the art would have been motivated by these teachings of Lefnaoui to
combine pregelatinized maize starch as a disintegrant with the compositions
of Arkenau-Maric, because the latter reference teaches that modified maize
starches are preferred disintegrants, and Lefnaoui teaches that pregelatinized
maize starch is a superior disintegrant.
Appellant questions how a person of ordinary skill in the art would
have known to look specifically to the teachings of Lefnaoui to select
pregelatinized maize starch as the “modified maize starch” taught by
Arkenau-Maric, and alleges this selection is reflective of impermissible
hindsight analysis by the Examiner. We disagree. A skilled artisan in the
art of dosage form design, would have had knowledge of disintegrants in
general, which are an integral part of dosage forms (see, e.g., Arkenau-Maric
¶ 31), and also of the specific teachings of Lefnaoui. See Custom
Accessories, Inc. v. Jeffrey-Allan Industries, Inc., 807 F.2d 955, 962 (Fed.
Cir. 1986) (holding that “[t]he person of ordinary skill is a hypothetical
person who is presumed to be aware of all the pertinent prior art”).
Consequently, a person of ordinary skill in the art would have been
motivated to use pregelatinized maize starch, so as to obtain the
advantageous qualities taught by Lefnaoui.
Appellant also argues that Lopez-Solis teaches that the ability for
starch to function as a disintegrant is dependent upon the water solubility
properties of the major components of the dosage form. We do not find that
this would dissuade a person of ordinary skill, because Arkenau-Maric
expressly teaches that modified maize starch is a preferred disintegrant with
its compositions. See App. Br. 12–13. Similarly, the teachings of Lopez-
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Soils and Lefnaoui concerning the identity and amount of starch to be used
in general, and the properties of pregelatinized maize starch in particular
(see id.), do not rebut the specific teachings of Lefnaoui concerning the
advantageous properties of pregelatinized maize starch, indeed, they would
act to further guide the skilled artisan in its employment.
Finally:
Any judgment on obviousness is in a sense necessarily a
reconstruction based upon hindsight reasoning, but so long as it
takes into account only knowledge which was within the level of
ordinary skill at the time the claimed invention was made and
does not include knowledge gleaned only from applicant’s
disclosure, such a reconstruction is proper.

In re McLaughlin, 443 F.2d 1392, 1395 (C.C.P.A. 1971). Appellant makes
no argument, nor adduces any evidence of record, to demonstrate that the
Examiner relied upon knowledge derived solely from Appellant’s
Specification and not from the teachings and suggestions of the prior art or
the knowledge of an artisan of ordinary skill. We consequently find
Appellant’s arguments to be without merit.

Issue 3
Appellant next argues that the Examiner failed to demonstrate that a
person of ordinary skill would have had a reasonable expectation of success
in combining the references. App. Br. 14.

Analysis
Appellant argues that the Examiner: (1) makes conclusory statements,
e.g., “[f]rom the teachings of the references, it is apparent that one of
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ordinary skill in the art would have had a reasonable expectation of success
in producing the claimed invention”; (2) cites Lefnaoui’s teaching regarding
the “‘excellent… dissolution properties’ of pregelatinized starch and
Fitzpatrick as teaching ‘resistance against solvent extraction’”; and (3)
makes findings that the dissolution properties of pregelatinized starch vary.
App. Br. 15 (citing Final Act. 8, 10, 11).
Appellant repeats the prior argument that the pending claims do not
recite “excellent dissolution properties,” rather, the pending claims recite a
specific dissolution profile. App. Br. 15. Similarly, Appellant argues, the
pending claims do not recite “resistance against solvent extraction,” but
recite resistance against solvent extraction by a specific method. Id.
Appellant argues further that the Examiner did not establish that
excellent dissolution properties or resistance to solvent extraction would
have been obvious for a given amount of pregelatinized starch. App. Br. 16.
Appellant contends that the Examiner makes a case that a low amount of
pregelatinized starch should show dissolution similar to crospovidone
(generally good), while a higher amount of pregelatinized starch should
show solvent extraction superior to crospovidone (generally not good). Id.
(citing Final Act. 10). However, Appellant argues, the Examiner nowhere
explains how the same amount of pregelatinized starch should or could
simultaneously exhibit dissolution properties similar to crospovidone, yet
also display solvent extraction properties that are a “night and day
difference” from crospovidone. Id.
Appellant also argues that the language cited by the Examiner (e.g.,
“varies,” “depends”) would undermine any skilled artisan’s reasonable
expectation of success, and further demonstrates the unpredictability of the
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art. App. Br. 16. Particularly, Appellant asserts, changing the identity and
amount of a component of a pharmaceutical dosage form unpredictably
changes the overall properties of the product. Id. Rather, Appellant
contends, the Examiner has not acknowledged the unpredictability of the art.
Id.
Finally, Appellant argues, the Examiner erroneously conflates a
result-effective variable with a reasonable expectation of success. App. Br.
16. Appellant points to the Examiner’s findings that “[t]he ordinary artisan
fully understands that… [but] the amount of pregelatinized starch
disintegrant is a result effective variable where larger amounts of
pregelatinized starch can gel and decrease dissolution” and “[c]onsequently
it is merely routine optimization within the amounts taught and suggested by
Arkenau-Maric” to arrive at the proper amount of pregelatinized starch to
achieve the dissolution limitation of the pending claims. App. Br. 16–17
(quoting Final Act. 10). Appellant asserts that, even though a component of
a composition may be considered a “results effective variable,” that does not
mean that an ordinary artisan would have had a reasonable expectation of
success. Id.
We fail to see the relevance of Appellant’s arguments. As we have
explained supra, Arkenau-Maric teaches that a modified maize starch is a
preferred disintegrant for its compositions, and Lefnaoui teaches that, among
modified starch disintegrants, pregelatinized maize starch has advantageous
properties as a disintegrant. Arkenau-Maric 31; Lefnaoui 699. We agree
with the Examiner that those teachings alone would be sufficient to give a
person of ordinary skill in the art of designing drug dosage forms a
reasonable expectation of success in combining the references.
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Furthermore, we have also explained why the burden showing that the
composition arrived at by combining the teachings of the references would
not obviously possess the properties recited by the functional limitations of
the claims rests with Appellant. See Best, 562 F.2d at 1254–55. Appellant
has not met this burden.
Finally, we agree with the Examiner that, Appellant’s burden
notwithstanding, a person of ordinary skill in the art of designing drug
dosage forms would understand that the amount of disintegrant (or other
constituent) in a given drug dosage form would be critical (i.e., a result-
effective variable) to the performance of that dosage form. See, e.g., Lopez-
Solis 131:
Starch 15002 can form, under certain conditions, a swollen
matrix that restricts the dissolution process. The problem with
this type of disintegrants is that they absorb water to produce
swelling and disintegration, but if the quantity of Starch 1500 is
big enough, the matrix does not disintegrate. The result would
be a sticky or gelatinous mass similar to hydrophilic sustained
release matrices, which resist break up of the tablets.

We therefore agree with the Examiner that it would have been well
within the skill of a person of ordinary skill in the art to optimize the amount
of pregelatinized maize starch to obtain the functional properties of the drug
dosage composition recited in the claims. See In re Boesch, 617 F.2d 272,
276 (C.C.P.A. 1980) (holding that “discovery of an optimum value of a
result effective variable … is ordinarily within the skill of the art”).

2 Starch 1500 is pregelatinized maize starch. Lopes-Solis 129; see also
Colorcon, Starch 1500®, available at: https://www.colorcon.com/products-
formulation/all-products/ excipients/tablets/starch-1500 (last visited
February 25, 2021).
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Issue 4
Appellant argues that the Examiner erred in failing to properly
consider Appellant’s rebuttal arguments and evidence. App. Br. 18.
Specifically, Appellant argues that the Examiner: (1) largely dismissed the
three Declarations of Dr. Klaus Wening, one of the named inventors (the
“Wening Declarations I–III,” filed August 22, 2018, January 15, 2019, and
June 10, 2019, respectively); and (b) misapplied the law of unexpected
results. Id. at 18, 23. We consider each argument in turn.

Analysis
1. The Wening Declarations
Appellant argues that, in Wening Declaration I, Dr. Wening discusses
the interplay between the claimed properties of dissolution rate and solvent
extraction. App. Br. 18 (citing, e.g., Wening Decl. I ¶¶ 3–7). According to
Appellant, Dr. Wening then reproduces the experiments reported as Example
5 in Appellant’s Specification, which demonstrate similar dissolution results,
but drastically different resistance to solvent extraction results for the same
disintegrants. Id. (citing Wening Decl. I ¶¶ 8–14). Appellant then points to
Dr. Wening’s testimony that the demonstrated results are “surprising and
unexpected.” Id. (citing Wening Decl. I ¶ 15).
Appellant next points to Wening Declaration II, in which Dr. Wening
testifies that “[i]t is evident that even in dosage forms such as Arkenau-
Maric’s that already contain polyethylene oxide[,] the presence of a
disintegrant can have a critical effect on the susceptibility of the dosage form
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to solvent extraction.” Ap. Br. 19 (citing Wening Decl. II ¶ 2). Dr. Wening
further opines that these results are “surprising and unexpected.” Id.
Appellant asserts that, in response, the Examiner finds that: (1)
Fitzpatrick teaches that “[c]rospovidone possesses unique pyrrolidone
chemistry and a highly porous particle morphology that results in high
surface area. The high surface area combined with unique chemistry results
in high-interfacial activity that serves to enhance the dissolution of poorly
soluble drugs in a way that is not possible with other disintegrant
technologies”; and (2) Bess teaches that it is expected that starches and
celluloses will serve as “separation inhibitors” for amine active agents such
as amphetamine, thereby enhancing resistance to solvent extraction. App.
Br. 19–20 (citing Non-Final Office Act. 9–10, filed June 27, 2019).
However, argues Appellant, the Examiner has not properly considered the
language of claim 95, which requires that the resistance to solvent extraction
and the dissolution profile occur simultaneously. Id. at 20. Appellant
asserts that the Examiner has not therefore explained why the results are
reasonably expected and more specifically, why both the solvent extraction
result and the dissolution profile result would have been expected. Id.
Appellant also disputes the Examiner’s finding that Wening I
compares the claimed pregelatinized starch to crospovidone (cross-linked
polyvinylpyrrolidone), the latter of which, the Examiner finds, does not
swell and form a gel. App. Br. 20 (citing Non-Final Act. 12–13). Appellant
argues, however, that the cited prior art does not suggest anywhere that the
same amount of pregelatinized starch could cause the dosage form to exhibit
a release of the active ingredient of at least 80 wt% within 30 minutes and
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simultaneously protect the dosage form from abuse by solvent extraction by
limiting the extractable amount of active ingredient. Id.
Appellant argues that, at most, the Examiner makes a case that a low
amount of pregelatinized starch should show dissolution similar to
crospovidone, whereas a higher amount of pregelatinized starch should show
solvent extraction superior to crospovidone. App. Br. 20. However, asserts
Appellant, the Examiner does not explain how the same amount of
pregelatinized starch could show similar dissolution to crospovidone, and
yet, simultaneously exhibit a difference to crospovidone in solvent
extraction resistance. Id. at 20–21.
Appellant argues further that the dosage forms tested by Dr. Wening
containing 20 wt% of either pregelatinized starch or crospovidone, more
than the approximately 12%, as taught by Lopez-Solis. App. Br. 21.
Appellant argues that the references cited by the Examiner suggest that the
dissolution properties of a dosage form containing high amounts of
pregelatinized starch would be negatively affected, compared to
crospovidone. Id. Appellant points to the Examiner’s finding that “[t]he
artisan fully understand that starch disintegrants and crospovidone can both
function with similar disintegration times and dissolution times when the
same low amount is employed.” Id. (quoting Final Act. 10 (citing Buhler)).
However, Appellant notes, Buhler does not teach using a pregelatinized
starch. Id. Appellant asserts that the Wening tests employ an amount of
starch greater than the 12% Lopez-Solis suggests as the swelling threshold.
Id. Therefore, argues Appellant, the same phenomenon that the Examiner
alleges leads to swelling and preventing the active ingredient from being
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drawn into a syringe would also prevent the active ingredient from
dissolving in Dr. Wening’s dissolution tests. Id. at 21–22.
Summarizing, Appellant argues that the Examiner fails to address
both sets of results together, and allegedly fails to appreciate that they are
coming from the same dosage form having a single, unchanging amount of
pregelatinized starch. App. Br. 22. Appellant contends that the Examiner
has not explained how this dosage form containing 20 wt% of pregelatinized
starch provides dissolution after 30 minutes is slightly superior to
crospovidone, and yet simultaneously provides solvent extraction results that
the Examiner admits are different from, and superior to, crospovidone. Id.
We do not find Appellant’s arguments persuasive. The experiments
summarized by Dr. Wening in Wening Declaration I demonstrate that:
In short, while all the formulations showed good in vitro
dissolution, from the standpoint of abuse of the dosage forms
there are stark differences. The data clearly and surprisingly
show that the choice of disintegrant is critical for this latter
property; and further that use of Haswani’s preferred
crospovidone may render the dosage form more susceptible to
this type of abuse. The use of the inventive polysaccharides,
starches, starch derivatives, cellulose derivatives and gas
releasing substances, on the other hand, are demonstrated to
increase the resistance of the dosage form to solvent extraction
abuse attempts. This remains surprising and unexpected in my
opinion.

Wening Decl. I ¶ 15 (emphasis omitted). Dr. Wening thus opines that use of
the genus comprising “inventive polysaccharides, starches, starch
derivatives, cellulose derivatives and gas releasing substances” as a
disintegrant displays superior properties to use of crospovidone as a
disintegrant, because although both demonstrate good dissolution properties,
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crospovidone displays markedly less resistance to solvent extraction than the
claimed pregelatinized maize starch, and therefore greater potential for
extraction of the drug and subsequent potential abuse. Dr. Wening therefore
concludes that this property of using the claimed “inventive polysaccharides,
starches, starch derivatives, cellulose derivatives and gas releasing
substances” as disintegrants is “surprising and unexpected.”
The relatively advantageous properties of pregelatinized maize starch
versus crospovidone as a disintegrant, as described by Dr. Wening, may
indeed be real, but that does not alter the fact that the prior art expressly
teaches the use of pregelatinized maize starch (a “modified maize starch”) as
a preferred disintegrant for use with potential drugs of abuse. See Arkenau-
Maric Abstr., ¶ 31; Lefnaoui 699. Dr. Wening may have demonstrated a
hitherto unappreciated property of using pregelatinized maize starch,
compared to crospovidone, when employed as a disintegrant, but that is not
sufficient to overcome the Examiner’s prima facie case of obviousness when
the combined teachings of the cited prior art teaches the use of
pregelatinized maize starch as a disintegrant used in dosage forms of
potential drugs of abuse. See In re Baxter Travenol Labs., 952 F.2d 388,
392 (Fed. Cir. 1991) (holding that “[m]ere recognition of latent properties in
the prior art does not render nonobvious an otherwise known invention”).
Appellant also argues that, in effect, Lopez-Solis teaches away from
using greater than 12% pregelatinized maize starch. See App. Br. 20 (noting
that “the Examiner also found that ‘Lopez-Solis et al. teach that Starch 1500
can form a swollen matrix that restricts dissolution process after about 12%
and can form a gelatinous mass’” (citing Lopez-Solis, 131), and arguing
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that, at concentrations greater that 12%, “the dissolution would be negatively
affected compared to crospovidone”).
We do not find this to reflect an accurate reading of the teachings of
Lopez-Solis. As an initial matter, the compositions tested in Lopez-Solis do
not reflect either the claimed compositions or those taught by the
combination of Arkenau-Maric and Lefnaoui. The latter references teach
compositions:
[C]ontaining least one active substance with potential for misuse
(A), at least one synthetic or natural polymer (C), optionally at
least one natural, semi-synthetic or synthetic wax (D), at least
one disintegrant (E) and optionally one or more additional
physiologically compatible excipients (B), wherein the
individual particles of the dosage form display a breaking
strength of at least 500 N and a release of active substance of at
least 75% after 45 minutes….

and where the disintegrant is pregelatinized maize starch. Arkenau-Maric
Abstr., ¶ 31, Lefnaoui, 699. By contrast, Lopez Solis compares the
dissolution properties of Norfloxacin (a fluoroquinolone antibiotic) and
Norfloxacin plus 25% Pharmatose DCL 11 (lactose monohydrate), when
varying concentrations of, inter alia, pregelatinized maize starch3 are used as
a disintegrant. See Lopez-Solis Abstr., 129. Consequently, a direct
comparison of the dissolution properties of the claimed compositions and
those of Lopez-Solis is not possible.
Indeed, the variability demonstrated by the results of the experiments
taught by Lopez-Solis demonstrates why a direct comparison of the Lopez-

3 See n.2 supra.
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Solis results to the dissolution properties of the claimed compositions is
confounded. Figure 2 of Lopez-Solis is reproduced below:

Figure 2 of Lopez-Solis depicts the effects of the addition of
Starch 1500® [pregelatinized maize starch] on percent
dissolution, at 30 min. of Norfloxacin and Norfloxacin plus
25% Pharmatose DCL 11 tablets.

Figure 2 of Lopez-Solis thus demonstrates that, for Norfloxacin (the
active ingredient alone), combination with greater than 12% pregelatinized
maize starch results in a decrease of the percent of Norfloxacin dissolution.
It is by no means evident from the data, however, that, at concentrations of
15%, or even 20% (as employed by Dr. Wening), the pregelatinized maize
starch “does not disintegrate […. forming] a sticky or gelatinous mass
similar to hydrophilic sustained release matrices….,” as argued by
Appellant. Lopez-Solis, 131.
However, Figure 2 also demonstrates that, when the active agent
Norfloxacin is combined with 25% Pharmatose DCL 11, the dissolution rate
at 15% does not demonstrate decreasing percent dissolution, but rather
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exhibits a steady-state between 12% and at least 15%. It is thus evident
from the teachings of Lopez-Solis that, at least, the dissolution properties of
an active agent in the presence of pregelatinized maize starch can be altered
by the presence of excipients, such as, e.g., 25% Pharmatose DCL 11 and
those recited in the claims. We therefore conclude that the teachings of
Lopez-Solis concerning the dissolution properties of pregelatinized maize
starch as a disintegrant are not comparable to its properties when employed
in the claimed compositions, and are therefore not probative of the
arguments made by Appellant.4 For these reasons, we do not find
Appellant’s arguments persuasive.

2. The law of unexpected results
Appellant next argues that the Examiner misapplies the law of
unexpected results. App. Br. 23. Appellant points to the Examiner’s finding
that: “Applicant has not compared pregelatinized starch against a modified
maize starch taught by Arkenau-Maric et al. Crospovidone is not the closest
prior art disintegrant. Therefore, Applicant’s Declaration data is not
probative and arguments relying upon the Declaration data are moot.” Id.
(quoting Final Act. 13). Appellant argues that Arkenau-Maric’s dosage

4 We also observe that Appellant expressly argues that the prior art teaches
that the ability of pregelatinized starch to function as a disintegrant in
pharmaceutical dosage forms depends upon, at least, the identity of the
particular pharmaceutical active agent. See App. Br. 12. This further
confounds comparisons between the experiments of Lopez-Solis, as
depicted in Figure 2 (which employ an antibiotic as the active agent), and
the compositions of Arkenau-Maric and the claims (which relate to
amphetamines, as well as various excipients).
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forms, as modified, in the rejection do not exist, and that the claimed dosage
forms are novel. Id. According to Appellant, hypothetical compositions
constructed by an Examiner in the making of an obviousness rejection
cannot possess properties, inherent or otherwise. Id. Appellant contends
that it was only when Appellant invented the claimed novel dosage form that
a dosage form was created whose properties could be ascertained. Id. (citing
In re Geiger, 815 F.2d 686, 689 (Fed. Cir. 1987)). In other words, argues
Appellant, requiring Appellant to compare the composition that is suggested
by the combination of references relied upon in the rejection of the claimed
invention under 35 U.S.C. § 103 “would be requiring comparison of the
results of the invention with the results of the invention.” Id. at 23–24
(quoting In re Chapman, 357 F.2d 418, 422 (C.C.P.A. 1966)).
We disagree. Arkenau-Maric teaches the structural elements of the
claimed composition, expressly teaching, inter alia, the use of modified
maize starch as a preferred disintegrant. Arkenau-Maric ¶ 31. Lefnaoui
teaches that pregelatinized maize starch is a modified maize starch with
advantageous properties. Lefnaoui 699. We agree with Appellant that the
cited prior art references do not teach the functional limitations recited by
claim 95. However, and as we have explained with respect to issue 1 supra:
Where, as here, the claimed and prior art products are identical
or substantially identical, or are produced by identical or
substantially identical processes, the PTO can require an
applicant to prove that the prior art products do not necessarily
or inherently possess the characteristics of his claimed
product.… Whether the rejection is based on ‘inherency’ under
35 U.S.C. § 102, on ‘prima facie obviousness’ under 35 U.S.C.
§ 103, jointly or alternatively, the burden of proof is the same,
and its fairness is evidenced by the PTO’s inability to
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manufacture products or to obtain and compare prior art
products.

Best, 562 F.2d at 1255 (citation omitted). The burden of evidence, then,
falls upon Appellant to show that the substantially identical composition
taught by the combined prior art references do not possess these functional
limitations. Appellant’s arguments and evidence, the opinions expressed in
the Wening Declarations notwithstanding, have, for the reasons we have
explained, not met this burden of proof. We consequently affirm the
Examiner’s rejection of the claims.

Issue 5
The Examiner has additionally provisionally rejected claims 95–101
as unpatentable under the nonstatutory doctrine of obviousness-type double
patenting over certain claims of the ’282, ’839, and ’643 applications. Final
Act. 15–17. Appellant’s Appeal Brief does not address these rejections. We
consequently summarily affirm this rejection. See 37 C.F.R.
§ 41.37(c)(1)(iv) (“[A]ny arguments or authorities not included in the appeal
brief will be refused consideration by the Board for purposes of the present
appeal.”).

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CONCLUSION
The Examiner’s rejection of claims 95–101 under 35 U.S.C. § 103 is
affirmed.
The Examiner’s provisional rejections of claims 95–101 under the
nonstatutory doctrine of obviousness-type double patenting are 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). See 37 C.F.R.
§ 1.136(a)(1)(iv).

AFFIRMED
Claim(s)
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
95–101 103 Arkenau-Maric,
Fitzpatrick, Heal,
Lefnaoui, Lopez-
Solis, Buhler

95–101
95–101 Obviousness-
Type Double
Patenting
’282, ’839, and
’643 applications 
95–101   
Overall
Outcome
    95–101