Ex Parte Schlutermann et al

Patent Trial and Appeal Board

Mar 22, 2019

11990100 (P.T.A.B. Mar. 22, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
11/990,100 04/11/2008
20999 7590 03/26/2019
HAUG PARTNERS LLP
745 FIFTH A VENUE - 10th FLOOR
NEW YORK, NY 10151
FIRST NAMED INVENTOR
Burkhard Schlutermann
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
ATTORNEY DOCKET NO. CONFIRMATION NO.
247004-203 2060
EXAMINER
PURDY, KYLE A
ART UNIT PAPER NUMBER
1611
NOTIFICATION DATE DELIVERY MODE
03/26/2019 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):
docket@haugpartners.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte BURKHARD SCHLUTERMANN and
MANFRED KOHLMEYER 1
Appeal2018-001473
Application 11/990, 100
Technology Center 1600
Before RICHARD M. LEBOVITZ, JOHN E. SCHNEIDER, and
DAVID COTTA, Administrative Patent Judges.
LEBOVITZ, Administrative Patent Judge.
DECISION ON APPEAL
This appeal involves claims directed to a pharmaceutical pellet
comprising a spherical core. The Examiner rejected the claims as obvious
under 35 U.S.C. § 103. Pursuant to 35 U.S.C. § 134, Appellants appeal the
Examiner's determination that the claims are unpatentable. We have
jurisdiction under 35 U.S.C. § 6(b ). The Examiner's decision is affirmed.
STATEMENT OF THE CASE
Claims 1--4, 6-10, 13-19, 24--33, and 37 stand rejected under 35
U.S.C. § 103(a) as obvious in view of Bai (US 5,840,329, issued Nov. 24,
1 The Appeal Brief ("Br." entered Apr. 7, 2017) lists ADD Advanced Drug
Delivery Technologies Ltd., as the real party in interest. Appeal Br. 1.
Appeal2018-001473
Application 11/990, 100
1998), Khan (US 2005/0112115 Al, published May 26, 2005), and Shimizu
et al. (WO 0006126, published Feb. 10, 2000) ("Shimizu"). Ans. 2.
Independent claim 1 is illustrative of the rejected claims and reads as
follows
1. A pharmaceutical pellet, comprising:
a spherical core with a smooth surface, the spherical core
comprising an active substance; and
a coating, on the core, which controls pH-independent
release of the active substance, and which does not comprise
the active substance;
wherein the core has a diameter in the range of from 0.2
to 2.0 mm; and
wherein the surface of the core has a mean roughness of
less than 10 µm and a relative mean roughness of less than 2%.
DISCUSSION
The Examiner found that Bai describes the claimed spherical core
with a coating that controls pH-independent release of a drug. Final Act. 4--
5. The Examiner found that Bai does not describe the core as having "a
mean roughness of less than 10 µm and a relative mean roughness of less
than 2%." To meet this limitation, the Examiner cited Khan as teaching that
"a smooth surface is desirable to prevent the blistering of the film, orange
peeling, uneven application of coating solutions or dispersion and mottling."
Id. at 6-7. The Examiner further cited Shimizu as describing a core
diameter overlapping with the diameter recited in the claims. Id. at 7 (i-f 20).
Appellants argue that Khan relates to a method of quantifying surface
roughness, and not of producing a product with a given surface roughness.
Appeal Br. 11. Appellants state that "Khan teaches that beads and granules
can be measured by the disclosed method, and not that beads and granules
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Application 11/990, 100
can be manufactured by any disclosed method." Id. at 12. Appellants
further argue:
Id.
The preparation of pellets or pellet cores is achieved by
particular granulation processes which are able to from
spherical pellets instead of relatively irregular granules. The
compression of a tablet from a powder or from granules plus
powder ( excipients, compression aids) or even from pellets plus
powder is a completely different process. Therefore, pellet
cores will not necessarily have the claimed values of surface
roughness given the disclosure of Khan about surface
roughness of tablets.
Appellants also contend that "Khan does not teach that a smooth
surface of a tablet was desirable." Appeal Br. 13. Rather, Appellants argue
that "Khan merely teaches that it was desirable to quantitatively measure the
surface roughness of tablets." Id.
We first begin with claim interpretation. The claim is directed to a
pellet comprising "a spherical core with a smooth surface, the spherical core
comprising an active substance." The core has a coating "which controls
pH-independent release of the active substance."
The Specification describes a core "as meaning that the entire inner
portion of the pellet [which] is enclosed beneath a coating that controls the
pH-independent release of the active substance. Spec. 12. The Specification
discloses examples of cores, including "seed cores coated with a layer of
active substance, where the layer of active substance can contain one or
more substance", "release-controlling coatings", and "protective coatings."
Id. See also claim 9 ("said spherical core comprises: a seed core not
containing the active substance; and a layer, on the seed core, which
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Application 11/990, 100
comprises the active substance."). Thus, a core can be made of a seed core
covered by a layer, including a layer comprising an active substance.
As discussed by the Examiner (Ans. 8), Khan describes coating beads
with a material comprising an active substance ("verapamil"). Khan ,r 68.
Khan teaches:
Initially the surface was rough and, at 4% weight gain, the
beads attained a relatively smoother surface. No additional
change in roughness was observed as a function of an increase
in coating weight gain. The drug-loaded beads appeared to be
porous and rough. However, coating reduced the surface
roughness and consequently a uniform film was formed.
Khan ,r 71.
Paragraph 71 of Khan states that the coating weight is increased until
a smoother surface was obtained, indicating the desirability of reducing
roughness and attaining a smoother surface. For this reason, we do not agree
with Appellants that Khan does not describe the manufacture of cores or that
"Khan does not teach that a smooth surface of a tablet was desirable."
Appeal Br. 13.
Khan teaches it is desirable to have smooth and uniform coating to
facilitate a uniform release of drug. For tablets, Khan teaches:
The Figure clearly demonstrates that a uniform membrane was
achieved at 10% wt. gain and that any further increase in
coating thickness would decrease the uniformity, resulting in an
unpredictable release pattern. For predictable membrane-
controlled dosage formulations, not only the weight gain of the
membrane matters but also the uniformity of the membrane.
Khan ,r 4 7. There is no reason to believe drug release from beads would be
any different than tablets with respect to diffusion through the surface
coating.
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While it may be true that, as asserted by Appellants (Appeal Br. 12),
the process described in the Specification results in pellets with a smooth
surface (Spec. 28-31 ), which differs from the tablet compression processes
described by Khan, Khan explicitly discloses a process of coating pellets
with a material to form a surface coating which is smooth and uniform.
Khan ,r 71. The definition of "core" in the Specification includes cores
having a coating. Spec. 12. Thus, while Khan's process differs from the
process described in the Specification, the claims are not limited to cores
made by a specific method. Khan, thus, describe a method of making
spherical cores having a smooth and uniform surface.
Appellants emphasize that "Khan is silent as to [ disclosing] any pellet
cores with the claimed roughness." Appeal Br. 14. As explained above, the
claims do not exclude the "spherical core" ( a pellet) from comprising a
coating. Khan teaches coated beads. Khan ,r 68. The coated beads are
described by Khan as having "relatively smoother surface." Khan ,r 71.
Appellants did not provide evidence that such "smoother" surface does not
have "a mean roughness of less than 10 µm and a relative mean roughness of
less than 2%." This is discussed in more detail below in the section titled
"Roughness measurements."
The Examiner found it would have been obvious to have modified Bai
to impart a smooth surface with the claimed mean roughness:
Here, the modification of Bai such that the surface to receive a
coating be made to have a surface roughness of 2.97 µm or 1.77
µm (see Table 3 of Khan) would have been obvious as applying
a known technique to a known product ready for improvement
to yield predictable results is indicative of prima facie
obviousness. See MPEP 2143(1)(D).
Ans. 7.
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Thus, it would have been obvious to one of ordinary skill in the art to
coat Bai' s seed as described in Khan to impart a smooth and uniform surface
to the seed, e.g., to give it predictable drug release rate. Again, Appellants
have not identified a deficiency in this reasoning.
Size
Appellants' argue that the diameter of the beads described in
paragraphs 68-71 of Khan does not meet the claimed limitation of "core has
a diameter in the range of from 0.2 to 2.0 mm." Reply Br. 11.
While the Examiner states that Khan's particles fall within the
claimed range (Ans. 9), the Examiner relied on paragraphs 68-71 of Khan to
establish that Khan described coating beads and measuring their mean
roughness. Ans. 8-9. The Examiner relied upon Shimizu as teaching
spherical particles with sizes that overlap with the claimed range. Final Act.
7 (i-f 20). Appellants in the Appeal Brief did not dispute the Examiner's
findings with regard to Shimizu and the obviousness of using its particles in
Bai. Appellants merely stated that "Shimizu does not teach how to prepare
pellet cores having the claimed smooth surface," ignoring the fact that the
Examiner did not rely on Shimizu for such a teaching. Appeal Br. 1 7.
Roughness measurements
The claim requires the spherical core to have "a mean roughness of
less than 10 µm and a relative mean roughness of less than 2%." The
Examiner found the ranges to be met by Khan's disclosure in Table 3 (citing
to the values listed in the table under the "Ra" roughness property). Final
Act. 6-7 (i-f 17). In the Reply Brief, Appellants argue that the roughness
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value of Ra pointed to by the Examiner in Table 3 is not the claimed
roughness value, but rather it is Rz, listed in the last column of Table 3,
which Appellants assert fall outside the claimed values for mean roughness.
Reply Br. 18-19.
First, we note that Appellants' response in the Reply Brief is a new
argument because the Examiner relied upon Table 3 in the Final Office
Action, and therefore Appellants' had the opportunity to respond to it in the
Appeal Brief, but did not. The argument is therefore waived because it was
first raised in the Reply Brief. 3 7 C.F .R. § 41.41 ( a )(2 ).
Even if we were to consider Appellants' improperly raised argument,
we would not be persuaded that the Examiner erred. The claim is drawn to
spherical cores having a "mean roughness of less than 10 µm." The
Specification defines "mean roughness" as a "root-mean-square value."
Spec. 15. Rz, cited by Appellants, is defined in Khan as "mean roughness
depth of the R-profile" and "mean peak to valley height." Khan ,r,r 11, 60.
It therefore does not appear that Rz is the same value as the "root-mean-
square value." Accordingly, Appellants did not establish that the Rz value
corresponds to the claimed "mean roughness."
The Examiner found in the Final Office Action that the Ra value
corresponded to the claimed "mean roughness."2 Final Act. 6-7 (i-f 17).
Appellants did not dispute this in the Appeal Brief, but rather waited until
the Reply Brief to address it. In the Reply Brief, Appellants made no
reference to how mean roughness is defined in the Specification and why it
would correspond to the Rz value, but not to the Ra value identified by the
2 The Examiner did not explicitly state "Ra," but pointed the Ra values in
Table 3.
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Examiner. Appellants simply made the assertion that Rz meets the claims
"mean roughness" without objective evidence to support the assertion.
Appellants also argue that no units for the R values are disclosed in
paragraphs 68-71 and Figure 4 (Reply Br. 12) in which the beads with a
smoother surface are manufactured. Figure 4 of Khan shows a graph of the
roughness parameters plotted as a function of coating weight gain. Khan
,r 71. The Y-axis does not describe the values as being in µm units.
However, the Examiner found that the units were in µm, which is consistent
with the fact that the values in Table 3 and Figure 3 of Khan are in µm. Ans.
8-9. We agree with this finding, particularly given that the examples
describe the same objective achieving a "decrease in roughness" (Kahn ,r 51)
for the tablets and "a relatively smoother surface" for the beads (Kahn ,r 71 ).
Applicants contend that Khan does not show values which meet the
claimed mean roughness. However, Figure 4 of Khan shows all roughness
values under 6 (including Ra and Rz) for the beads produced in paragraphs
68-71. Appellants have not adequately explained why these values do not
meet the claim limitation regarding mean roughness, except to argue that
that the units are not shown. In addition to this, as discussed above, the
values in Table 3 for Ra also fall within the scope of claim 1. Appellants
have not provide adequate evidence that this teaching would not have been
extended to beads as a desired roughness value, Thus, Khan shows, as well
as suggests, roughness values for coated beads within the claimed range and
describes how to manufacture them to have a smooth and uniform surface.
Appellants have not provided evidence that the claimed values are
critical or any different from those in Khan.
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While Appellants continued to dispute that Khan provides a reason to
make a pharmaceutical dosage having a smooth surface, Khan repeatedly
refers to achieving a smooth surface (i1i19, 37, 47, 49, 50, 52, 71) and
reasons for doing so: to achieve predictable drug release (i-f 47) and to have
a sufficient coating (i-f 37). For example, in addition to what has already
been cited, Khan teaches:
If the tablets are smooth initially, improper or insufficient
coating will produce higher surface roughness values. Once the
coating is complete, the surface roughness values should
decrease.
Khan ,r 37.
The increase in compression pressure from 0.5 Ton to 1.25 Ton
dramatically decreased the surface roughness (see Table 2).
Nevertheless, a further increase in compression pressure did not
decrease the roughness proportionately, perhaps because a
decrease in roughness goes in parallel with an increase in the
hardness of the tablet. There is a saturation point in the
decrease in roughness, above which any additional compression
pressure may not facilitate a reduction in smoothness
Khan ,r 51.
Even if the above disclosures are in reference to tablets, we have not
been presented with an adequate reason why they would not be applicable to
a spherical bead or pellet. The reasoning that a smooth uniform surface
would lead to predictable drug release rates would be the same for a tablet
and spherical bead because both have outer surfaces through which the drug
must be released.
Non-analogous art
Appellants argue that Khan is non-analogous art because it is not
within the inventor's field of endeavor. Appellants state: "The current
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Application relates to producing a pellet as a dosage form for an active
substance. In contrast, Khan relates to a method of measuring surface
roughness of a dosage form. Khan, [0003]-[0011]." Appeal Br. 15.
Appellants further argue that "Khan has nothing whatsoever to do with
producing a pellet. Thus, it is clear that Khan is not within the field of the
instant inventors' endeavors." Id. at 16.
This argument is not persuasive because Khan describes coating
pellets to achieve a smooth uniform surface and reduce mean roughness.
Khan ,r,r 68-71. The claims are directed to pellets having a particular degree
of mean roughness. Consequently, Khan's teaching of how to measure
surface roughness is clearly pertinent to the claims. Appellants' arguments
about the inventors endeavor relating to "addressing problems associated
with providing a pharmaceutical pellet for which the release of the active
substance can be controlled independently of the pH value and
independently of the action of enzymes" (Appeal Br. 17) ignore the explicit
language in the claim of spherical cores having "a mean roughness of less
than 10 µm and a relative mean roughness of less than 2%", values
addressed by Khan's disclosure.
Claim 2
Claim 2, depends from claim 1, and further recites "wherein the core
has a length-width ratio of less than about 1.4." The Examiner found that
because particles described in Shimizu are spherical, it would be expected
that the ratio between width and length would be 1.0. Final Act. 7.
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Appellants argue that there is no teaching in Bai, Khan, or Shimizu
about the sphericalness of any particles or granules. Appeal Br. 18. This
argument does not persuade us that the Examiner erred.
As found by the Examiner, Shimizu describes a "spherical product"
having a size which overlaps with the claimed range. Shimizu 16-17
(Section "7)"). The spherical product is made of crystalline cellulose and
lactose (a sugar). Id. Bai teaches that its seed is made or sugar/starch or
cellulose. Bai 6:3. Shimizu's spherical product therefore contains the same
components as in Bai, making it obvious to have used it in Bai's method for
its equivalency to Bai's seed. Final Act. 7 (i-f 20). Since Shimizu
characterizes its product as "spherical," and a "sphere" has the meaning of
"an object that is completely round in shape like a ball" as defined in a
general purpose dictionary, 3 one of ordinary skill in the art would reasonably
expect the width and length to about the same and about 1. 0 as found by the
Examiner.
Appellants state the depending on the method used to make it, the
resulting shape of the pellet core may be more irregular than a sugar sphere,
but provide no objective evidence to support this argument. Appeal Br. 18-
19. Moreover, the issue in this rejection is the sphericalness of Shimizu 's
product which the Examiner found could be utilized in Bai' s method.
Appellants' have not provided evidence that such product which is
characterized as "spherical" by Shimizu would not have core has a length-
width ratio of less than about 1.4 and fall outside the scope of the claim.
The teaching in Shimizu that the product is "spherical" was sufficient to
3 https://www.collinsdictionary.com/us/dictionary/english/sphere_l
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shift the burden to Appellants to show that it did not meet the limitations of
the claim.
Summary
For the foregoing reason, the obviousness rejection of claims 1 and 2
is affirmed. Claims 3, 4, 6-10, 13-18, 24--33, and 37 were not argued
separately and fall with claim 1. 37 C.F.R. § 4I.37(c)(l)(iv).
Claim 19
Appellants make the same arguments for claim 19, that they do for
claims 1 and 2. The rejection of claim 19 is affirmed for the same reasons.
TIME PERIOD
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(l )(iv).
AFFIRMED
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