Ex Parte Petereit et al

Patent Trial and Appeal Board

Mar 8, 2018

10532831 (P.T.A.B. Mar. 8, 2018)

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
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APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
10/532,831 03/09/2006 Hans-Ulrich Petereit 267336US0PCT 8866
22850 7590 03/12/2018
OBLON, MCCLELLAND, MAIER & NEUSTADT, L.L.P.
1940 DUKE STREET
ALEXANDRIA, VA 22314
EXAMINER
WESTERBERG, NISSA M
ART UNIT PAPER NUMBER
1618
NOTIFICATION DATE DELIVERY MODE
03/12/2018 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):
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PTOL-90A (Rev. 04/07)
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 2016-003903
Application 10/532,831
Technology Center 1600
Before RICHARD M. LEBOVITZ, JEFFREY N. FREDMAN, and
ELIZABETH A. LaVIER, Administrative Patent Judges.
FREDMAN, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal1,2 under 35 U.S.C. § 134(a) involving claims to a
multilayer dosage form. The Examiner rejected the claims as obvious. We
have jurisdiction under 35 U.S.C. § 6(b). We affirm.
Statement of the Case
Background
“The use of so-called neutral methacrylate copolymers, which are
methacrylate copolymers which consist predominantly of (at least 95%)
(meth)acrylate monomers with neutral radicals, such as methyl methacrylate
1 Appellants identify the Real Party in Interest as Evonik Rohin GMBH {see
App. Br. 2).
2 We note that this case was subject to a previous appeal, Appeal 2011-
000113, dated Nov. 9, 2012.
Appeal 2016-003903
Application 10/532,831
or ethyl acrylate, as coating agents and binders for dosage forms with
delayed release of active substances has been known” (Spec. 1:14-20). The
prior art teaches multilayer dosage forms that permit “the adjustment of
variable release profiles and a delivery of active substance which is precise
and reproducible under defined conditions” (Spec. 3:20-23).
However, “[production thereof is comparatively complicated due to
the multilayer structure” and one “problem is that the active substance
release characteristics are evidently influenced by the ionic strength of the
surrounding medium (Spec. 3:25-26, 4:3-5).
The Claims
Claims 1-3, 8, 9, 13, 14, and 17-20 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,
c) an outer coating which comprises a copolymer that is
composed of 40 to 60% by weight methacrylic acid and 60 to
40% by weight methyl methacrylate or ethyl acrylate, and
d) optionally an emulsifier and/or a release agent,
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%.
2
Appeal 2016-003903
Application 10/532,831
The Issue
The Examiner rejected claims 1-3, 8, 9, 13, 14, and 17-20 under 35
U.S.C. § 103(a) as obvious over Ulmius3 and Beckert4 (Ans. 2-6).
The Examiner finds Ulmius teaches “multilayer compositions of
corticosteroids” with “a core and two layers on that core” where the “core
can either be formulated with the glucocorticosteroid homogenously
throughout the core or the active ingredient can be applied to the exterior of
the seed” (Ans. 2). The Examiner finds EUDRAGIT® NE 30D is a
preferred methacrylate copolymer “that meets the monomer requirements for
the inner coating” and “as the composition of [EUDRAGIT® NE 30D and
the claimed polymers] are the same, the film-forming temperature of the
polymer will necessarily meet the [recited] limitations” (Ans. 3).
The Examiner finds Ulmius teaches a release profile “such that no
release occurs in the stomach but is released in either the small intestine or
caecum” (Ans. 3). The Examiner finds Ulmius teaches application of
second layers of EUDRAGIT® L or S to the core (id.).
The Examiner acknowledges Ulmius “does not explicitly prepare a
composition in which the active ingredient is provided in a EUORAGIT®
NE 300 layer with an outer coating of EUORAGIT® L or S” (Ans. 3).
The Examiner finds the multilayer dosage form of claim 1 obvious
because “selection of the polymer components for the various layers from
those disclosed by Ulmius et al. is well within the skill of the person of
3 Ulmius, J., US 5,643,602, issued July 1, 1997.
4 Beckert et al., WO 01/68058 Al, published Sept. 20, 2001 (the Examiner
relies upon US 2002/0192282 Al, published Mar. 9, 2001, as the English
language translation of the German WO document).
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Application 10/532,831
ordinary skill in the art” (Ans. 4). The Examiner further finds it obvious “to
determine the optimal amount of each ingredient to add in order to best
achieve the desired results such as the particular release profile of the active
agent” {id.).
The issues with respect to this rejection are:
(i) Does the evidence of record support the Examiner’s conclusion
that Ulmius and Beckert render claim 1 obvious?
(ii) If so, have Appellants presented evidence of secondary
considerations, that when weighed with the evidence of obviousness, is
sufficient to support a conclusion of non-obviousness?
Findings of Fact
1. Ulmius teaches “oral pharmaceutical compositions for use in
the treatment of inflammatory bowel diseases and the use of certain
glucocorticosteroids” (Ulmius 1:10-12).
2. Ulmius teaches: “Each unit comprises a core, a first layer on the
core and a second layer on the first layer” (Ulmius 5:3—4).
3. The Specification teaches “neutral cores for the coatings are
tablets, granules, pellets, crystals of regular or irregular shape. The size of
granules, pellets or crystals is usually between 0.01 and 2.5 mm” (Spec. 7:6-
9).
4. Ulmius teaches the “core consists of a non-pareil seed,
preferably having a diameter between 0.2 and 1.0 mm” (Ulmius 5:5-6).
5. The Specification teaches a first coating of “Eudragit® NE 30
D (copolymer of 65% by weight ethyl acrylate and 35% by weight methyl
methacrylate)” (Spec. 26:10-12; emphasis omitted).
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Application 10/532,831
6. Ulmius teaches the “first layer on the non-pareil seeds
comprises the glucocorticosteroid and a water-soluble or water-insoluble
polymer . . . Preferred film-forming polymers are ethylcellulose or
copolymers of acrylic and methacrylic acid esters (Eudragit NE, Eudragit
RL, Eudragit RS) in aqueous dispersion form” (Ulmius 5:12-27).
7. The Specification teaches, regarding the outer coating, that
“Suitable anionic (meth)acrylate copolymers are those composed of 40 to
60% by weight methacrylic acid and 60 to 40% by weight methyl
methacrylate or 60 to 40% by weight ethyl acrylate (Eudragit® L or
Eudragit® L 100-55 types)” (Spec. 19:38 to 20:3).
8. Ulmius teaches “[t]he polymers in the second layer may be
selected from the group of anionic carboxylic polymers suitable for
pharmaceutical purposes and being soluble with difficulty at a low pH but
being soluble at a higher pH . . . such as Eudragit L, Eudragit LI00-55 and
Eudragit S” (Ulmius 5:34 42).
9. Ulmius teaches
When the dosage form has been emptied from the stomach the
transit through the small intestine takes 3 to 5 hours. The
residence time in the large intestine is considerably longer, 25
to 50 hours. Ideally, as long as the dosage form remains in the
stomach no release should occur. If Crohn’s disease in small
intestine is going to be treated the release should continue
during about 5 hours after the dosage form has left the stomach.
(Ulmius 4:30-39).
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Application 10/532,831
10. Figures 5 and 6 of the Specification are reproduced below:
£is. 5
“The release investigation, the results of which are depicted graphically in
Fig. 5, shows that the release from the pellet behaves very robustly in respect
of changes in the release medium.” (Spec. 33:15-18). Figure 6 shows
“Release profiles of Example 6 aminosalicylic acid pellets with a release-
slowing coating of Eudragit RL 30 D and a gastro-resistant coating of
Eudragit L 30 0-55 in phosphate buffer differing in osmolarity” (Spec. 34:3-
V)
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Application 10/532,831
Principles of Law
The Examiner has the initial burden of establishing a prima facie case
obviousness under 35 U.S.C. § 103. In re Oetiker, 977 F.2d 1443, 1445
(Fed. Cir. 1992). “The combination of familiar elements according to
known methods is likely to be obvious when it does no more than yield
predictable results.” KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416
(2007).
Prima facie obviousness can be rebutted by presenting evidence of
secondary considerations and when such evidence is submitted, all of the
evidence must be considered anew. In re Piasecki, 745 F.2d 1468, 1472-
1473 (Fed. Cir. 1984). Secondary considerations include: long-felt but
unsolved needs, failure of others, unexpected results, commercial success,
copying, licensing, and praise. In re Rouffet, 149 F.3d 1350, 1355 (Fed. Cir.
1998).
Analysis
We adopt the Examiner’s findings of fact and reasoning regarding the
scope and content of the prior art (Ans. 2-6; FF 1-10) and agree that claim 1
is obvious over Ulmius and Beckert. We further agree that the “wherein”
clause of claim 1, relating to a 10% difference in percentage release values
in hypotonic versus isotonic release medium, corresponds to an inherent
property of a dosage form comprising the specific and obvious amounts of
core a), inner coating b) and outer coating c) as recited in claim 1. The
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); see also In re Zierden, 411 F.2d 1325, 1328 (CCPA 1969)
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Application 10/532,831
(stating that a “mere statement of a new use for an otherwise old or obvious
composition cannot render a claim to the composition patentable”).
Appellants contend:
The data of record shows that it is the selection of the inner
coating polymer in which the active is bound/embedded that
leads to the unexpected effect in terms of the percentage release
in various release medium. Specifically, Figure 5 includes an
inner NE30 coating with the addition of the outer
gastrointestinal resistant L30D (Copolymer of 50%
ethylacrylate and 50% methacrylic acid) and resulted in no
substantial difference in the different media whereas Figure 6 is
similar to Figure 5 with the only difference being the inner
coating polymer (changed from NE30D to RL30D) with the
same outer coating polymer (L30 D-55 is a copolymer of 50%
ethylacrylate and 50% methacrylic acid) but with this change in
the inner coating polymer there was clearly a variance in the
release under different media.
(App. Br. 4-5).
We find this argument unpersuasive because Appellants provide no
evidence that this result is unexpected or surprising to one of ordinary of
ordinary skill in the art, whether by way of Declaration or citation to a
statement in the Specification. “Mere improvement in properties does not
always suffice to show unexpected results. . . . [HJowever, when an
applicant demonstrates substantially improved results, . . . and states that
the results were unexpected, this should suffice to establish unexpected
results in the absence of evidence to the contrary In re Soni, 54 F.3d 746,
751 (Fed. Cir. 1995).
We also agree with the Examiner that:
[t]he compositions tested and the drug release shown in
examples 5 and 6 differ in more than the polymer used for the
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Application 10/532,831
inner coating layer. The amounts of Eudragit®, active
substance, talc, TEC and water differ and the active substances
themselves are not the same - aminosalicylic acid in figure 6
and budesonide in figure 5.
(Ans. 7). A comparison of two very different compositions provides no
evidence or support for a finding that any particular one of the differences
resulted in any change in properties.
Appellants contend: “Rather than considering Applicants’ showing of
unexpected results as rebuttal evidence to an alleged prima facie case, the
Examiner has dismissed it and, in fact, has clearly convinced herself that
unexpected results cannot exist when she thinks she has made a prima facie
case” (App. Br. 7).
We find this argument unpersuasive. The Examiner directly
considered the asserted evidence but found it insufficient for the reasons
given above. As we noted in the previous appeal in this application,
“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” (Appeal
2011-000113, slip op. at 8). Appellants do not address these concerns and
provide no evidence supporting why data for different active substances can
be compared on release rates to demonstrate that the other components are
causing the difference, rather than the different active substances
themselves.
Conclusion of Law
(i) The evidence of record supports the Examiner’s conclusion that
Ulmius and Beckert renders claim 1 obvious.
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Application 10/532,831
(ii) Appellants have not presented evidence of secondary
considerations, that when weighed with the evidence of obviousness, is
sufficient to support a conclusion of non-obviousness.
SUMMARY
In summary, we affirm the rejection of claim 1 under 35 U.S.C.
§ 103(a) as obvious over Ulmius and Beckert. Claims 2, 3, 8, 9, 13, 14, and
17-20 fall with claim 1.
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
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