Ex Parte Geerke et al

Board of Patent Appeals and Interferences

Sep 24, 2008

09324343 (B.P.A.I. Sep. 24, 2008)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte JOHAN H GEERKE and STEVEN F. STONE
__________

Appeal 2008-4075
Application 09/324,343
Technology Center 1600
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Decided: September 24, 2008
__________

Before DONALD E. ADAMS, LORA M. GREEN, and
FRANCISCO C. PRATS, Administrative Patent Judges.

PRATS, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to methods
of making three-layer capsule-shaped tablets. The Examiner has rejected the
claims as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We
reverse.

Appeal 2008-4075
Application 09/324,343

STATEMENT OF THE CASE
Osmotic dosage forms for drug delivery consist of an “internal
compartment containing at least one drug-containing layer, at least one
expandable polymer-containing layer and, optionally, one or more drug-free
layers to produce a desired release pattern such as delayed or pulse release”
(Spec. 2). The internal compartment “is surrounded by a membrane that is
at least partially semipermeable and at least one delivery port is formed
through the membrane at an appropriate location to permit release of drug-
containing formulation from within the compartment” (id.).
The expandable polymer layer “is known as a ‘push’ layer because,
following oral administration, fluid is imbibed through the semipermeable
membrane causing the drug-containing layer(s) and any optional drug-free
layer(s) to form a dispensable formulation and causing the polymer layer to
expand and ‘push’ the dispensable formulation through the delivery port”
(id.). Because of the importance of the delivery port’s location, a colorant is
used to distinguish the different layers from each other, thereby allowing
drilling of the appropriate portion of the tablet, usually by laser, to produce
the delivery port (id. at 3).
The Specification discloses “methods of making multi-layer capsule-
shaped osmotic tablets having an appropriate color scheme to facilitate
determination of the tablet formulation orientation by color detection at a
spot location on the side of the tablet” (id. at 4).
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Claims 18-20, 32, 33, 35, and 36 stand rejected and are on appeal
(App. Br. 2-3).1 Claims 18 and 20, the appealed independent claims, are
representative and read as follows:
18. A method of making a three-layer capsule-shaped tablet
comprising:
formulating a first layer containing a drug ingredient and
a second layer containing a drug ingredient, wherein one of the
layers comprises a first colorant;
formulating a non-drug ingredient containing third layer
comprising a second colorant that is distinguishable from the
first colorant or from no color and not containing any drug
ingredient;
compressing the first, second and third layers into a
capsule-shaped osmotic tablet wherein the first layer is located
at one end of the capsule-shaped osmotic tablet and the third
layer is located at the other end of the capsule-shaped osmotic
tablet and the second layer is located between the first layer and
the third layer such that the formulation orientation of the tablet
can be determined by detecting the color at a spot location on a
side of the tablet corresponding to one or another differently-
colored layer depending on the formulation orientation of the
tablet; and
detecting the formulation orientation of the tablet with a
color detector directed at a spot location on the side of the
tablet.

20. A method of making a three-layer capsule-shaped tablet
comprising:

1 Appellants state that the appeal has been withdrawn with respect to claim
38 (App. Br. 2-3). When prosecution resumes in this case the Examiner and
Appellants should work together to ensure that claim 38 is canceled. See Ex
Parte Ghuman,
http://www.uspto.gov/web/offices/dcom/bpai/prec/rm081175.pdf, slip op. at
5-6 (Bd. Pat. App. & Int. May 1, 2008) (precedential).

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formulating a first layer containing a drug ingredient and
not containing any colorant;
formulating a second layer containing a drug ingredient
and a first colorant, the first colorant being complementary to
no color;
formulating a third layer containing a second colorant
that is distinguishable from the first colorant or from no color
and not containing any drug ingredient;
compressing the first, second and third layers into a
capsule-shaped osmotic tablet the first layer is located at one
end of the capsule-shaped osmotic tablet and the third layer is
located at the other end of the capsule-shaped osmotic tablet
and the second layer is located between the first layer and the
third layer such that the formulation orientation of the tablet can
be determined by detecting the color at a spot location on a side
of the tablet corresponding to one or another differently-colored
layer depending on the formulation orientation of the tablet; and
detecting the formulation orientation of the tablet with a
color detector directed at a spot location in the side of the tablet.

The Examiner cites the following documents as evidence of
unpatentability:
Barclay US 5,248,310 Sep. 28, 1993
Riddle US 5,294,770 Mar. 15, 1994
Wong US 5,785,994 Jul. 28, 1998

OBVIOUSNESS
ISSUE
Claims 18-20, 32, 33, 35, and 36 stand rejected under 35 U.S.C.
§ 103(a) as being unpatentable over Barclay in view of Wong and Riddle
(Ans. 3-8).
The Examiner cites Barclay as disclosing two-layered osmotic tablets
having separate polymer and drug-containing layers that are distinguishable
from each other by a coloring agent in the non-drug polymer-containing
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layer (Ans. 4). The Examiner states that Barclay “compresses the drug and
non-drug layer together and coats the resultant solid osmotic tablet with a
translucent coating” (id. (citing Barclay, col. 17, ll. 39-51)), a hole being
then drilled through the coating to the drug-containing layer of the tablet to
allow release of the drug from the capsule (Ans. 5).
The Examiner contends that Barclay differs from the claims in that
“Barclay only fails to explicitly teach a three-layered tablet and further use a
color detector to orient the tablet formulations” (id.). The Examiner cites
Wong and Riddle “to show the general knowledge in the art to make a three
layer tablet or use a color detector to orient tablet formulations during their
manufacturing process” (id).
Specifically, the Examiner cites Wong as disclosing a “three or more
layered tablet that provides a varying pattern of drug release . . . . Such
pattern is achieved by drug concentrations in each layer of Wong’s
formulation. Wong et al. disclose that their tablets are prepared by pressing
the three layers to form a solid core” (id. at 5-6). The Examiner further
contends that Wong’s tablets have “three layers wherein [the] first layer is
drug free and is a push layer which contains a colorant such as ferric oxide .
. . and the third layer comprise a colorant . . . . Thus, adding additional drug
layers is well within the scope of Wong’s teachings” (id. at 6 (citations
omitted)).
The Examiner further contends that “[t]he only difference between
Barclay and Wong is that Barclay teaches a two layer osmotic tablet, but
Wong teaches a three layer osmotic tablet. Nevertheless, their combined
teachings do not explicitly teach the use of a color detector during their
manufacturing process” (id. at 7). The Examiner cites Riddle as disclosing
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the use of a color detector to aid in drilling the access port in the coating of
tablets of the type disclosed by Barclay and Wong (id.).
Based on these teachings, the Examiner concludes:
[I]t would have been obvious to one ordinary skilled in
the art at the time of invention to employ Barclay’s method of
detecting different layers in the three layer osmotic dosage
forms of Wong, by incorporating a coloring agent, as shown by
Barclay, in any desired layer, because the ordinary skill in the
art would have had a reasonable expectation of success to use
different colorants to facilitate ease of detection of each
formulation layer and even further employ a color detector such
as those described by Riddle to differentiate the orientation of at
the tablets during their manufacturing process for any suitable
step such as creating a delivery port.

(Ans. 8).
Appellants contend that the Examiner has failed to establish a prima
facie case of obviousness “because combination of the respective teachings
of the cited patents, even if motivated, would not have produced any claimed
invention” (App. Br. 3). Specifically, Appellants argue that the capsule-
shaped osmotic dosage forms produced by the methods recited in
independent claims 18 and 20 have a “drug/drug/no drug orientation” which
is neither taught nor suggested by the cited prior art (id.). Appellants further
argue that the Examiner’s contention, that the claimed methods would have
been within the skill in the art, is insufficient to establish a prima facie case
of obviousness “[b]ecause the Examiner failed to identify any objective
evidence that it would have been obvious (or even possible) to modify the
teachings of the prior art in a way that would have produced the three-layer,
drug/drug/no drug orientation of the present invention” (id. at 6).
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The issue with respect to this rejection, then, is whether the Examiner
has made a prima facie case that one of ordinary skill in the art would have
considered claims 18-20, 32-33, 35, and 36 obvious in view of Barclay,
Wong, and Riddle.
FINDINGS OF FACT
1. Barclay discloses “an osmotic device for the controlled delivery of a
beneficial agent to the oral cavity of an animal, and in particular a human,
for an extended period of time” (Barclay, col. 4, ll. 4-6).
2. Figure 3 of Barclay, reproduced below, shows “a side sectional view
of the osmotic device” (Barclay, col. 5, l. 59):

The figure shows device 10, which is “comprised of a wall 12 that
surrounds and forms a compartment 13 . . . . Compartment 13 comprises a
layer of a beneficial agent, identified by dots 14, that can be from insoluble
to very soluble in an exterior aqueous fluid, indicated by dashes 15”
(Barclay, col. 6, ll. 16-21). Barclay discloses:
Compartment 13 further houses a layer of an expandable
driving member 16 composed of a hydrophilic polymer,
optionally cross-linked, which possesses osmotic properties
such as the ability to imbibe external fluid and exhibit an
osmotic pressure gradient across the wall 12 against the fluid.
Wall 12 is substantially impermeable to the passage of the
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hydrophilic polymer in driving layer 16. Layer 16 absorbs fluid
imbibed into the compartment and swells.

(Id. at col. 6, ll. 40-48.)
3. Barclay discloses that, driven by the expanding polymer layer 16,
device 10 “releases agent 14 through one or more passageways 17 in wall 12
that communicates agent 14 with the exterior of device 10” (Barclay, col. 7,
ll. 1-3).
4. Barclay discloses an example of producing the osmotic dosage form
by preparing a white-colored drug-containing layer, and a reddish-brown-
colored hydrophilic polymer-containing layer colored with ferric oxide, and
pressing the two layers together in a tableting machine (Barclay, col. 17, ll.
20-40 (Example 2)). Barclay discloses that “[t] he hydrophilic polymer
layer had a reddish-brown color, due to the ferric oxide, providing a good
color contrast with the white drug-containing layer (id. at col. 17, ll. 40-43).
The two-layered tablet is then coated with a semipermeable wall through
which a single osmotic passageway is drilled into the drug-containing layer
(id. at col. 17, ll. 43-57).
5. Barclay does not disclose an osmotic dosage form having two drug
layers immediately adjacent to each other, with a non-drug layer at one end
of the dosage form, and one of the two drug layers at the other end.
6. Wong discloses “a dosage form provided as an osmotic device
comprising means for the rate-programmed delivery of a drug in time-
varying patterns to a drug recipient” (Wong, col. 1, ll. 18-20). In one
embodiment, Wong’s dosage form “delivers a first or instant dose of drug at
bed-time for providing drug during sleep, and a second or delayed drug early
in the morning for providing drug therapy on awakening from sleep” (id. at
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col. 2, ll. 37-40). Wong discloses that administering such a dosage at
bedtime is suitable for treating high blood pressure, because of the rise in
blood pressure that occurs upon waking (id. at col. 1, ll. 46-56).
7. Figure 4 of Wong, reproduced below, depicts “a dosage form
manufactured as a programmable dosage form that provides time-varying
patterns of drug delivery including drug-free intervals between drug doses of
various drug-release durations including instant drug delivery and prolonged
drug delivery with the latter delivered through a multiplicity of exit
passageways” (Wong, col. 3, ll. 7-13):

Wong describes the outer components of the dosage form shown in Figure
4 as follows:
Coat 14 provides instant drug therapy, as film coat 14
dissolves or undergoes dissolution in the presence of fluid and
concurrently therewith delivers drug 15 to drug receptor. Coat
14 comprising drug 15 provides (1) instant drug followed by a
drug-free interval, and (2) it essentially overcomes the time
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required for drug 15 to be delivered from the interior of dosage
form 10.

(Wong, col. 3, ll. 54-60.)
Figure 4 also shows wall 12, which is permeable to an exterior fluid
but not to the drug contained within the compartment (id. at col. 4, ll. 19-60),
with a multiplicity of passageways 13, that allow the drug 15 within the
capsule to exit (id. at col. 13, l. 64 through col. 14., l. 6).
8. Wong discloses that the inner components of the dosage form shown
in Figure 4, include “[l]ayer 18 [which] is drug-free. Layer 18 . . . provides
a drug-free interval between drug 15 delivered from outside coat 14 and
drug delivered from inside compartment 17” (Wong, col. 5, ll. 24-27).
Wong states that the drug-free first layer 18 “comprises a member selected
from the group consisting of an osmagent 19, represented by V, and an
osmopolymer 20, represented by squares. First layer 18 optionally
comprises a binder 21 represented by wavy lines” (id., col. 5, ll. 28-32).
9. Wong discloses that the inner components of the dosage form shown
in Figure 4 also include “[d]rug layer 22 [which] comprises a drug 15,
represented by dots” (Wong, col. 9, ll. 39-40), and which also can contain
suitable drug carriers (id. at col. 12, ll. 1-39).
10. Wong discloses that the inner compartment of the dosage form shown
in Figure 4 also has “a third layer 24 or push layer” (Wong, col. 12, l. 40),
described as follows:
The push third layer 24 comprises an osmopolymer suitable for
forming the third osmotic push layer 24. The third layer
comprises an osmopolymer that exhibits fluid imbibition
properties. The osmopolymers are swellable, hydrophilic
polymers which osmopolymers interact with water and aqueous
biological fluids and swell or expand to an equilibrium state.
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The osmopolymers exhibit the ability to swell in water and
retain a significant portion of the imbibed water within the
polymer structure. The osmopolymers swell or expand to a
very high degree, usually exhibiting a 2 to 60 fold volume
increase.

(Wong, col. 12, ll. 41-51)
11. Wong discloses an example of preparing the osmotic dosage form by
preparing a drug-free layer, a drug-containing layer, and a polymeric push
layer containing ferric oxide, and pressing the three layers onto each other
with a tableting die (Wong, col. 19, l. 54, through col. 20, l. 38). The three-
layered tablet is then coated with a semipermeable wall through which a
single drug exit port is drilled into the drug-containing layer (id. at col. 20,
ll. 38-53). A quick release composition containing the same drug contained
within the osmotic compartment is then coated onto and compressed around
the semipermeable wall (id. at col. 20, ll. 54-64.)
12. Wong does not disclose an osmotic dosage form having two drug
layers immediately adjacent to each other, with a non-drug layer at one end
of the dosage form, and one of the two drug layers at the other end.
13. Neither Barclay nor Wong explicitly discloses detecting the
formulation orientation of the disclosed osmotic dosage forms with a color
detector.
14. Riddle discloses an apparatus for “laser drilling for forming drug
release ports in pharmaceutical tablets” (Riddle, col. 1, ll. 6-8). Riddle
discloses that its device is capable of distinguishing between the differently
colored layers of a two layer osmotic tablet to drill drug release ports in the
correct, i.e. drug-containing, side of the tablet (id. at col. 7, ll. 11-33).
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15. Riddle does not disclose an osmotic dosage form having two drug
layers immediately adjacent to each other, with a non-drug layer at one end
of the dosage form, and one of the two drug layers at the other end.
PRINCIPLES OF LAW
“In proceedings before the Patent and Trademark Office, the
Examiner bears the burden of establishing a prima facie case of obviousness
based upon the prior art.” In re Fritch, 972 F.2d 1260, 1265 (Fed. Cir.
1992). “[O]bviousness requires a suggestion of all limitations in a claim.”
CFMT, Inc. v. Yieldup Intern. Corp., 349 F.3d 1333, 1342 (Fed. Cir. 2003)
(citing In re Royka, 490 F.2d 981, 985 (CCPA 1974)).
Emphasizing a flexible approach to the obviousness question, the
Supreme Court has nonetheless similarly noted that “it can be important to
identify a reason that would have prompted a person of ordinary skill in the
relevant field to combine the elements in the way the claimed new invention
does . . . because inventions in most, if not all, instances rely upon building
blocks long since uncovered, and claimed discoveries almost of necessity
will be combinations of what, in some sense, is already known.” KSR Int'l
Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) (emphasis added); see also
id. at 1740-41 (requiring a determination of “whether there was an apparent
reason to combine the known elements in the fashion claimed by the patent
at issue”) (emphasis added).
ANALYSIS
We agree with Appellants that the Examiner has not made a prima
facie case that one of ordinary skill in the art would have considered claims
18-20, 32, 33, 35, and 36 obvious in view of Barclay, Wong, and Riddle.
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Independent claims 18 and 20 both recite the step of “compressing the
first, second, and third layers into a capsule-shaped osmotic tablet” such that
“the first [(drug-containing)] layer is located at one end of the capsule-
shaped osmotic tablet and the third [(non-drug-containing)] layer is located
at the other end of the capsule-shaped osmotic tablet and the second [(drug-
containing)] layer is located between the first layer and the third layer.”
Thus, as Appellants argue, claims 18 and 20 both require preparation of an
osmotic dosage form that has a “drug/drug/no drug” orientation (App. Br. 3).
In contrast, Barclay discloses an osmotic tablet that contains only a
single drug layer and a single non-drug layer (see FF 2-4). Barclay therefore
differs from the claims in that Barclay’s dosage form does not contain two
drug layers adjacent to each other.
While Wong discloses a formulation that has two drug-containing
layers (FF 6, 7), only one of those layers (22) is compressed into the osmotic
dosage form, the other drug layer being coated about the entire exterior of
the dosage form on the semipermeable layer (FF 7-9). Also, the interior
compartment of Wong’s osmotic dosage form contains a non-drug layer (18)
between the outer drug coating and the drug-containing layer (FF 7, 8).
Thus, the interior compartment of Wong’s osmotic dosage form contains a
drug layer (22) that lies between the non-drug push layer (24) at one end of
the compartment, and the non-drug layer (18) adjacent to the exit port at the
other end of the compartment (FF 7, 9-11).
The Examiner has not explained why Wong’s disclosure of a dosage
form having two drugs separated by a non-drug layer, with one of the drugs
being coated outside the entire osmotic compartment, would have prompted
one of ordinary skill in the art to place an additional drug-containing layer
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adjacent to the drug layer of Barclay’s osmotic dosage form. Nor has the
Examiner explained how Barclay’s disclosure of a single drug-containing
osmotic dosage form would have prompted one of ordinary skill to eliminate
the non-drug layer separating the two medicaments in Wong’s dosage form,
and replace it with a drug containing layer to achieve the orientation of the
product made in independent claims 18 and 20.
Instead, the Examiner’s sole rationale for modifying the prior art
processes to arrive at the claimed processes is that “preparing a two or three
layer osmotic tablet and using a color detector to orient a tablet are well
within the level of an ordinary skill in the art,” as evidenced by Wong and
Riddle, which, respectively, “show the general knowledge in the art to make
a three layer tablet or use a color detector to orient tablet formulations during
their manufacturing process” (Ans. 5; see also 8-9).
However, as discussed above, neither Wong nor Riddle discloses that
it was desirable to include two drug layers adjacent to each other in an
osmotic dosage form. Rather, in embodiments that use two drugs, Wong
discloses the desirability of providing a two-phase drug dosage by including
one drug layer within the osmotic compartment and the other drug layer
coating the entire outside of the osmotic compartment, the two layers being
separated by a non-drug layer (FF 7-11).
The Examiner simply has not explained how an osmotic dosage form
configured in the manner disclosed in Wong would have prompted one of
ordinary skill in the art to prepare an osmotic dosage form by “compressing
the first, second, and third layers into a capsule-shaped osmotic tablet” such
that “the first [(drug-containing)] layer is located at one end of the capsule-
shaped osmotic tablet and the third [(non-drug-containing)] layer is located
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at the other end of the capsule-shaped osmotic tablet and the second [(drug-
containing)] layer is located between the first layer and the third layer,” as
recited in independent claims 18 and 20.
As the Supreme Court has pointed out, “[r]ejections on obviousness
grounds cannot be sustained by mere conclusory statements; instead, there
must be some articulated reasoning with some rational underpinning to
support the legal conclusion of obviousness.” KSR, 127 S. Ct. at 1741
(quoting In re Kahn, 441 F.3d 977, 988, (Fed. Cir. 2006) (emphasis added).
We agree with Appellants that, by simply averring to the general knowledge
of one of ordinary skill in the art, without any supporting rationale based on
the prior art or scientific reasoning, the Examiner has failed to provide the
rational underpinning required to support a prima facie case of obviousness.
Thus, because the Examiner has failed to provide sound scientific
reasons or specific evidence as to why one of ordinary skill in the art
viewing these references would have placed two drug layers immediately
adjacent to each other in an osmotic tablet in the configuration required by
independent claims 18 and 20, we are compelled to reverse the Examiner’s
obviousness rejection of those claims and their dependents.

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SUMMARY
We reverse the Examiner’s rejection of claims 18-20, 32, 33, 35, and
36 under 35 U.S.C. § 103(a) as being unpatentable over Barclay in view of
Wong and Riddle.

REVERSED

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