Ex Parte Petereit et al

Patent Trial and Appeal Board

Nov 7, 2012

10532831 (P.T.A.B. Nov. 7, 2012)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte HANS-ULRICH PETEREIT, MARKUS RUDOLPH,
JENNIFER DRESSMAN, and THOMAS BECKERT
__________

Appeal 2011-000113
Application 10/532,831
Technology Center 1600
__________

Before JEFFREY N. FREDMAN, STEPHEN WALSH, and
JACQUELINE WRIGHT BONILLA, Administrative Patent Judges.

BONILLA, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims directed to a
multilayer dosage form comprising a core and inner and outer coatings
comprising methacrylate copolymers. The Examiner has rejected the claims
as obvious. We have jurisdiction under 35 U.S.C. § 6(b). An oral hearing
was held November 2, 2012. We affirm.

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STATEMENT OF THE CASE
The Specification describes a multilayer dosage form with a neutral
methacrylate copolymer as a binder for the active substance (Spec. 1). The
Specification states that in prior art multilayer dosage forms ―active
substance release characteristics are evidently influenced by the ionic
strength of the surrounding medium,‖ i.e., depend on water and food intake
in vivo, which may ―lead to active ingredient substances release
characteristics which are not always reproducible‖ (id. at 4).
Claims 1-3, 8, 9, 13, 14 and 16 are on appeal. Independent claim 1 is
representative and reads as follows:
1. A multilayer dosage form comprising
a) a neutral core,
b) an inner methacrylate copolymer coating comprising at least
90% by weight of (meth)acrylate monomers having neutral radicals,
wherein the methacrylate copolymer has a minimum film-forming
temperature as specified in DIN 53 787 not exceeding 30°C, and a
pharmaceutically active substance bound to the methacrylate polymer,
wherein the inner coating does not comprise plasticizer; and
c) an outer coating which comprises a (meth)acrylate
copolymer which is composed of 10 to 30% by weight methyl
methacrylate, 50 to 70% by weight methyl acrylate and 5 to 15% by
weight methacrylic acid,
wherein the values for the percentage release of active
substance in a hypotonic and an isotonic release medium based on
phosphate buffer pH 6.8 do not differ from one another at any time in
the period from 1 to 5 hours by more than 10%.
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All pending claims stand rejected under 35 U.S.C. § 103(a) as (I)
obvious over Ulmius
1
in view of Beckert et al.,
2
and (II) obvious over
Ulmius in view of Gang et al.
3

I.
Issues
The Examiner rejects pending claims as obvious over Ulmius

in view
of Beckert (Ans. 4). The Examiner finds that Ulmius discloses a multilayer
dosage form having a neutral core, the inner coating b) of claim 1, i.e., an
inner coating comprising a relevant methacrylate polymer, Eudragit
®
NE
30D, and a pharmaceutically active substance (budesonide) bound to the
methacrylate polymer, and an outer coating (id. at 4-5). The Examiner
acknowledges that Ulmius does not disclose a multilayer dosage form
having an inner layer comprising Eudragit
®
NE 30D with an outer layer as
recited in c) of claim 1, such as Eudragit
®
FS (id. at 5). The Examiner finds
that Beckert discloses a similar multilayer dosage form having a neutral
core, an inner polymer coating, and the outer coating c) of claim 1, i.e., an
outer coating comprising a relevant methacrylate polymer, Eudragit
®
FS
(id.).

1
Ulmius, U.S. Pat. No. 5,643,602, issued Jul. 1, 1997
2
Beckert et al., WO 01/68058 (citations from the English equivalent U.S.
Pat. Appl. Publ. No. 2002/0192282 A1, published Dec. 19, 2002).
3
Gang et al., Studies on Coated Theophylline Tablets for Colon-Specific
Delivery System Using Eudragit NE
®
30D, 7 PROCEEDINGS OF THE 7TH SCEJ
165-169 (2001) (cited on IDS submitted Jul. 23, 2009).

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The Examiner concludes it would have been obvious to use the outer
coating of Beckert in the dosage form described in Ulmius (id. at 6). The
Examiner also notes that the ―discovery of a previously unappreciated
property of a prior art composition, or of a scientific explanation for the
prior art’s functioning, does not render the old composition patentably new
to the discoverer‖ (Ans. 9-10 (quoting Atlas Powder Co. v. Ireco Inc., 190
F.3d 1342, 1347 (Fed. Cir. 1999), and citing In re Best, 562 F.2d 1252, 1254
(CCPA 1977)).
Appellants assert that although Ulmius describes an inner layer
including different types of polymers, such as Eudragit® polymers, none of
the Examples in Ulmius describe an inner coating comprising the polymer
recited in b) of claim 1 (App. Br. 8). According to Appellants, neither
Ulmius nor Beckert provides the necessary direction to select polymer b) of
claim 1 as an inner coating (id. at 8, 12). Appellants also argue that Beckert
teaches away from the claimed dosage form because this reference places
the active substance onto the core and not bound in the inner coating, and
uses a different Eudragit
®
inner coating (id. at 12).
In addition, Appellants argue that it was unknown, and one would not
have predicted nor had a reasonable expectation of success, that the dosage
form recited in claim 1 ―was not affected by the ionic strength of the
dissolution medium‖ (id. at 8-12, 5-7). Appellants emphasis the
―unexpected‖ result of similar active substance release in hypotonic versus
isotonic release medium, as recited in the last clause of claim 1, relying on
Examples 1, 5, and 6, and Figures 2, 5, and 6 in the Specification (id. at 5-7,
9-12).
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The issues with respect to this rejection are: Does the Examiner
present a prima facie case of obviousness of claim 1 over Ulmius

in view of
Beckert, and if so, do Appellants come forward with arguments and/or
evidence sufficient to rebut a conclusion of obviousness based on a totality
of the evidence?
Findings of Fact
1. Both Ulmius and Beckert teach relevant multilayer dosage forms
comprising a core, inner coating, and outer coating, for the preferential
release of an active drug, such as a glucocorticosteroid, to the colon (Ulmius,
col. 4, ll. 50-60; col. 5, ll. 2-4; Beckert [0001], [0006], [0043]).
2. Ulmius teaches that the inner layer comprises an active substance and
a polymer that acts ―both as a binder for‖ the active substance and as ―a rate-
limiting layer for release‖ of active substance (Ulmius, col. 5, ll. 12-17).
3. Regarding the inner layer, Ulmius further teaches that ―[p]referred
film-forming polymers are ethylcellulose or copolymers of acrylic and
methacrylic acid esters (Eudragit NE, Eudragit RL, Eudragit RS)….‖
(Ulmius, col. 5, ll. 24-27.)
4. Ulmius discloses that an outer layer may comprise ―partly esterified
methacrylic acid polymers such as Eudragit L, Eudragit L100-55 and
Eudragit S,‖ but does not expressly refer to Eudragit
®
FS (Ulmius, col. 5, ll.
32-48).
5. Beckert teaches that an inner coating may comprise methacrylate
copolymers, but Beckert does not refer to Eudragit
®
NE or indicate that the
inner coating comprises an active ingredient (Beckert [0074] – [0082]).
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6. Becker discloses that ―[p]articularly suitable (meth)acrylate
copolymers‖ for the outer coating are ―those composed of 10 to 30% by
weight methyl methacrylate, 50 to 70% by weight methyl acrylate and 5 to
15% by weight methacrylic acid (EUDRAGIT
®
FS type)‖ (id. at [0087]).
Analysis
We agree with the Examiner that it would have been prima facie
obvious to create a multilayer dosage form having all elements recited in
claim 1 (Ans. 6). Because both Ulmius and Beckert describe relevant
multilayer dosage forms for the preferential release of an active drug, such
as a glucocorticosteroid, to the colon (FF 1), one would have had reason to
use the outer coating of Beckert (comprising Eudragit® FS) in the dosage
form of Ulmius having the inner coat comprising Eudragit
®
NE (e.g.,
Eudragit
®
NE 30D) and a pharmaceutically active substance (FF 2-6).
We disagree with Appellants that Beckert (or any other cited
reference) teaches away from the claimed dosage form (App. Br. 12) simply
because the reference(s) describes different dosages forms. As correctly
noted by the Examiner, a ―prior art’s mere disclosure of more than one
alternative does not constitute a teaching away from any of these alternatives
because such disclosure does not criticize, discredit, or otherwise discourage
the solution claimed ….‖ (Ans. 12 (quoting In re Fulton, 391 F.3d 1195,
1201 (Fed. Cir. 2004)).
We also find, and Appellants do not dispute, that the ―wherein‖ clause
of claim 1, relating to a small difference in percentage release values in
hypotonic versus isotonic release medium, corresponds to an inherent
property of a dosage form comprising core a), inner coating b) and outer
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coating c) as recited in claim 1. Case law indicates that recognition of latent
properties ―does not render nonobvious an otherwise known invention.‖ In
re Baxter Travenol Labs, 952 F.2d 388, 392 (Fed. Cir. 1991); In re Zierden,
411 F.2d 1325, 1328 (CCPA 1969) (stating that a ―mere statement of a new
use for an otherwise old or obvious composition cannot render a claim to the
composition patentable‖); see also Ans. 9-10).
Moreover, In re Kubin addresses the question of whether inherency
may be used in an obviousness analysis. Alcon Research, Ltd. v. Apotex
Inc., 687 F.3d 1362, 1369 (Fed. Cir. 2012) (quoting In re Kubin, 561 F.3d
1351, 1357 (Fed. Cir. 2009). Specifically, Kubin states that inherency
applies if the ―application itself instructs that [the wherein element] is not an
additional requirement imposed by the claims [on the recited
composition]…, but rather a property necessarily present in the [recited
composition].‖ (Id. (quoting Kubin, 561 F.3d at 1357); see also In re Huai-
Hung Kao, 639 F.3d 1057, 1070 (Fed. Cir. 2011) (similarly quoting Kubin).)
We find that the record here indicates, as found by the Examiner (Ans. 9-
10), that the ―wherein‖ clause of claim 1 recites an inherent property without
providing any additional requirement on the recited dosage form beyond that
recited in a), b) and c) of claim 1 (see, e.g., Spec. 4-5; App. Br. 5).
Because the Examiner presents a prima facie case of obviousness, we
consider whether Appellants submits sufficient evidence or argument in
rebuttal. In re Rijckaert, 9 F.3d 1531, 1532 (Fed. Cir. 1993). Evidence
rebutting a prima face case of obviousness may include ―[e]vidence of
unexpected results.‖ Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1369 (Fed.
Cir. 2007).
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Asserting unexpected results, Appellants refer to Examples 1, 5, and
6, and Figures 2, 5, and 6 in the Specification (App. Br. at 5-7, 9-12).
According to Appellants, Example 1 has budesonide (active substance)
embedded in an inner coating of Eudragit
®
NE 30D (encompassed by b) in
claim 1) but has no outer coating; Example 5 adds the outer coating of
Eudragit
®
L30D-55 (encompassed by c) in claim 1); and Example 6 has the
same outer coating as Example 6, but has a different inner coating of
Eudragit
®
RL 30D (not encompassed by b) in claim 1) (id. at 5-6). Citing
results shown in Figures 2, 5, and 6, Appellants assert the following:
These results show that the replacement of Eudragit® NE30D
with Eudragit® RL30D as the inner coat to which the active is bound
had differential release depending on the osmotic conditions of the
release medium. Taken together, Examples 1, 5 and 6 as well as FIGs
2, 5 and 6 demonstrate that the inner methacrylate polymer, e.g.,
Eudragit® NE30D was responsible for this unexpected effect.
(Id. at 7.)
Notably, however, Examples 1, 5 and 6 differ from one another,
leading us to find that Appellants compare apples to oranges in relation to
the cited data. For example, the Specification indicates that the inner coat of
Example 5 is the same as the inner coat of Example 3, not Example 1 (Spec.
29, Table). Elsewhere, the Specification indicates that Example 1 differs
from Example 3 (and therefore Example 5) in the amount of Eudragit® NE
30D, budesonide, talc, TEC, and water present in the inner coating (id. at 27,
Table). Most notably, however, is the difference between Example 5 and 6.
Not only do the amounts of Eudragit®, active substance, talc, TEC, and
water differ between these two examples, but Example 6 includes a different
active substance altogether, i.e., aminosalicylic acid, rather than budesonide
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(id. at 34). Thus, Appellants’ arguments asserting ―unexpected results‖
based on this data do not carry persuasive weight.
After an Appellant provides argument or evidence in response to an
Examiner’s prima facie case, we determine patentability ―on the totality of
the record, by a preponderance of evidence with due consideration to
persuasiveness of argument‖ submitted by Appellant. In re Oetiker, 977
F.2d 1443, 1445 (Fed. Cir. 1992). Here, Appellants’ arguments and
evidence relating to unexpected results do not persuade us that the Examiner
fails to establish that claim 1 would have been obvious by a preponderance
of the evidence. Because Appellants do not argue the dependent claims
separately, claims 2, 3, 8, 9, 13, 14, and 16 fall with claim 1. 37 C.F.R.
§ 41.37(c)(1)(vii).
Conclusion of Law
We conclude that the Examiner presents a prima facie case of
obviousness of claim 1 over Ulmius

in view of Beckert. Further, Appellants
do not provide arguments and/or evidence sufficient to rebut a conclusion of
obviousness based on a totality of the evidence.
II.
Issue
Does the Examiner present a prima facie case of obviousness of claim
1 over Ulmius

in view of Gang, and if so, do Appellants come forward with
arguments and/or evidence sufficient to rebut a conclusion of obviousness
based on a totality of the evidence?
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Additional Finding of Fact
7. Gang discloses ―a colon specific drug delivery system, which
comprises a conventional tablet coated with Eudragit
®
NE 30D and an outer
coat of pH-dependcnt polymer Eudragit® FS‖ (Gang 165, ¶3 of
Introduction). Gang teaches coating theophylline tablets (a core) with these
inner and outer coatings (id. at 165, abstract; 166).
Analysis
As noted by the Examiner, Gang discloses the exact combination of
inner and outer polymers in inner and outer coatings as recited in claim 1,
although this reference does not expressly teach binding an active substance
to the methacrylate polymer in the inner coat (FF 7; Ans. 14, App. Br. 14).
Ulmius, relating to a similar multilayer dosage system, teaches that the inner
layer may comprise an active substance and a polymer (Eudragit
®
NE
30D—same inner coating polymer as in Gang) that acts ―both as a binder
for‖ the active substance and as ―a rate-limiting layer for release‖ of active
substance (FF 2; Ans. 6).
We agree with the Examiner that it would have been prima facie
obvious to create a multilayer dosage form having all elements recited in
claim 1 in light of these references (Ans. 8). Because both Ulmius and Gang
describe relevant multilayer dosage forms for the preferential release of an
active drug to the colon (FF 1, 7), one would have had reason to use the
outer coating of Gang (comprising Eudragit® FS) in the dosage form of
Ulmius having the inner coat comprising Eudragit
®
NE (e.g., Eudragit
®
NE
30D) and a pharmaceutically active substance (FF 2-4).
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While the Examiner presents a prima facie case of obviousness, we
must again consider whether Appellants submits sufficient evidence or
argument in rebuttal. In relation to this rejection, Appellants rely on the
same asserted unexpected results discussed above based on Examples 1, 5,
and 6, and Figures 2, 5, and 6 in the Specification (App. Br. 14-15). Thus,
for the same reasons already mentioned, Appellants’ arguments and
evidence relating to unexpected results do not persuade us that the Examiner
fails to establish that claim 1 would have been obvious by a preponderance
of the evidence. Because Appellants do not argue the dependent claims
separately, claims 2, 3, 8, 9, 13, 14, and 16 fall with claim 1. 37 C.F.R.
§ 41.37(c)(1)(vii).
Conclusion of Law
We conclude that Examiner presents a prima facie case of
obviousness of claim 1 over Ulmius

in view of Gang. Further, Appellants do
not provide arguments and/or evidence sufficient to rebut a conclusion of
obviousness based on a totality of the evidence.
SUMMARY
We affirm the rejection of claims 1-3, 8, 9, 13, 14 and 16 under 35
U.S.C. § 103(a) as obvious over Ulmius in view of Beckert, as well as the
rejection of the same claims as obvious over Ulmius in view of Gang.

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TIME PERIOD FOR RESPONSE
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).

AFFIRMED

cdc