Ex Parte Kolter et al

Patent Trial and Appeal Board

Oct 11, 2018

13416558 (P.T.A.B. Oct. 11, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
13/416,558 03/09/2012
20995 7590 10/15/2018
KNOBBE MARTENS OLSON & BEAR LLP
2040 MAIN STREET
FOURTEENTH FLOOR
IRVINE, CA 92614
UNITED ST A TES OF AMERICA
FIRST NAMED INVENTOR
Karl Kolter
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.
BASF.040A 1014
EXAMINER
CABRAL, ROBERTS
ART UNIT PAPER NUMBER
1618
NOTIFICATION DATE DELIVERY MODE
10/15/2018 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):
j ayna.cartee@knobbe.com
efiling@knobbe.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte KARL KOLTER, SILKE GEBERT, SANDRA KRUSE, and
MICHAELSCHONHERR
Appeal2017-000602
Application 13/416,558 1
Technology Center 1600
Before DONALD E. ADAMS, RICHARD M. LEBOVITZ, and
RACHEL H. TOWNSEND, Administrative Patent Judges.
TOWNSEND, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a
pharmaceutical formulation in the form of granules, which have been
rejected as anticipated. We have jurisdiction under 35 U.S.C. § 6(b).
We reverse.
STATEMENT OF THE CASE
"Tablets which rapidly disintegrate and/or rapidly dissolve in the
mouth are achieving ever greater importance for the oral administration of
drugs." (Spec. 1.) "Rapidly disintegrating tablets often consist of sugars
and sugar alcohols, ... [and] customary disintegrants." (Id.) In addition to
1 Appellants identify the real party in interest as BASF SE. (Appeal Br. 3.)
Appeal2017-000602
Application 13/416,558
being able to disintegrate within a short time, rapidly disintegrating tablets
"should be easy to manufacture ... have high mechanical strength so that
they withstand packaging procedures, transportation and also the squeezing
out from packs in an undamaged manner." (Id.) The invention relates to a
pharmaceutical formulation in the form of granules that can be used in
rapidly disintegrating tablets. (Spec. 3.)
Claims 1-13 are on appeal. 2 Claim 1 is representative and reads as
follows:
1. A pharmaceutical formulation in the form of granules,
the granules comprising
a) about 60-96% by weight of one or more non-film-
forming sugars or sugar alcohols,
b) about 1-10% by weight of one or more film-forming
sugars or sugar alcohols,
c) about 3-25% by weight of one or more disintegrants,
d) about 0-10% by weight of one or more water-
insoluble, film-forming polymers, and
e) about 0-15% by weight of one or more
pharmaceutically customary auxiliaries,
wherein the sum of components a) to e) is 100% by
weight, wherein components a) to e) are in the form of
agglomerates in the granule.
(Appeal Br. Claims Appendix filed Jan. 21, 2016)
2 Claims 14--23 are also pending, but have been withdrawn from
consideration. (Final Action (Office Action Summary: "Disposition of
Claims* 5)".)
2
Appeal2017-000602
Application 13/416,558
The following ground of rejection by the Examiner is before us on
review:
Claims 1-13 under 35 U.S.C. § I02(b) (pre-AIA) as anticipated by
Norman. 3
DISCUSSION
The Examiner finds that Norman teaches a co-processed carbohydrate
system that includes a co-processed carbohydrate, such as mannitol and
sorbitol, plus a disintegrant (e.g., cross-linked polyvinylpyrrolidone
("PVP")) and a glidant. (Ans. 3--4; Non-final Action dated Oct. 3, 2013, 2-3
("Non-final 2013").) The Examiner explains that the sugar alcohols are
present in the composition in the claimed range and that the composition is a
quick dissolving composition that can be directly compressible. (Non-final
2013.) The Examiner further contends that Norman teaches "that '[p]article
size can range from 0.1 to 500 microns." (Id. at 3.)
The Examiner notes that"[ w ]hile Norman may not expressly state that
the 'co-processed carbohydrate system' has the ingredients in the form of
agglomerates in the granule, the 'co-process carbohydrate system' is
believed to result in agglomerates of the ingredients since the process is
understood to be similar to that used for the instant claimed composition."
(Non-final Action dated Oct. 3, 2014, 3 ("Non-final 2014").) In this regard,
the Examiner notes that "both use a liquid solution of the film forming sugar
alcohol mixed with the other ingredients (cf para [0086] of the instant
specification and page 11, lines 18-20 of Norman), which afterward the
composition is spray-dried in a spray drier which 'can also be used for
3 Norman et al., WO 03/05133 Al, published June 26, 2003.
3
Appeal2017-000602
Application 13/416,558
agglomerating, congealing, encapsulating, cooling and/or conditioning the
composition of the present invention.' See page 11, line 29--page 12, line 4."
(Id.)
In addition to the foregoing, the Examiner notes that "Norman teaches
that the 'co-processed system is superior over simply the dry-blending of
ingredients." (Final Action 3.4) The Examiner explains that Norman
teaches at pages 11-12 that the spray drying equipment's main use is for
drying "but the equipment can also be used for agglomerating . .. the
composition of the present invention," which includes a "co-processed
carbohydrate system." (Ans. 4.) The Examiner concludes that from this
disclosure, one of ordinary skill in the art would understand that "the 'co-
processed carbohydrate system' would agglomerate as well." (Id.) The
Examiner also explains that the spray-drying process of Norman results in
agglomerates and that the "[a]ddi[tion] of a disint[e]grant has not been
show[ n] to prevent agglomerate even if added after the fact." (Final Action
2-3.)
We disagree with the Examiner's factual finding that Norman would
have been understood by one of ordinary skill in the art to teach a
composition that includes mannitol (the non-film-forming sugar alcohol of
a) of claim 1 ), sorbitol (the film-forming sugar alcohol ofb) of claim 1 ), and
a disintegrant ( component c) of claim 1) that together form an agglomerate
in a granule as required by all the rejected claims. In particular, we note that
the Examiner's conclusion is premised on the position that Norman's
process for forming the co-processed carbohydrate system is similar to that
4 The Final Action is dated May 7, 2015.
4
Appeal2017-000602
Application 13/416,558
described in the specification for forming the agglomerate. We disagree
with the Examiner's premise.
The present Specification identifies mannitol as a non-film forming
sugar alcohol, sorbitol as a film-forming sugar alcohol, and cross-linked
PVP as a disintegrant. (Spec. 3:12-18; see also claims 3, 4, and 5.) The
Specification explains that the non-film-forming sugar alcohol (mannitol) is
introduced along with the disintegrant (e.g., cross-linked PVP) and
agglomerated with an aqueous solution of the film-forming sugar alcohol
(sorbitol). (See, e.g., Spec. 4:17-19; 9:16-27; 10:9-20; 15:15-20.) The
Specification notes that the agglomeration can "take[] place in a fluidized-
bed granulator, mixer, paddle dryer or spray tower" (Spec. 4:24--25; see also
9: 17-19) and describes each such process (Spec. 10: 10-13: 11).
In particular, the Specification teaches that "to give granules" in the
fluidized bed process there is an "initial charge" of powder that is a
"fluidizing mixture of non-film-forming sugar or sugar alcohol and
crosslinked PVP." (Spec. 9: 24--26.) The Specification explains further that
cross-linked PVP can also be suspended in the aqueous film-forming sugar
alcohol granulating liquid. (Spec. 9:29-31.) However, that does not change
the fact that non-film-forming sugar alcohol and disintegrant are first
combined as the initial charge and then mixed with the aqueous solution of
film-forming sugar alcohol.
The Specification describes production of granules in spray towers,
similarly, involving the introduction of the non-film-forming sugar alcohol
to the cross-linked PVP and then spraying in the aqueous solution of the
film-forming sugar alcohol. (Spec. 10:9-20.) Thus, like the fluidized bed
process, the non-film-forming sugar alcohol and disintegrant are first
5
Appeal2017-000602
Application 13/416,558
combined and then added to an aqueous solution of the film-forming sugar
alcohol.
For a granulation process in a multistage spraying process, the
Specification indicates an initial charge of materials ( defined earlier as a
fluidizing mixture of non-film-forming sugar or sugar alcohol and cross-
linked PVP) is wetted either with water or a low concentration of the
aqueous spray solution of film-forming sugar alcohol and then the
concentration of the aqueous spray solution of film-forming sugar alcohol is
increased to start agglomeration to granules. (Spec. 11 :25-32.) Thus, here
again, the non-film-forming sugar alcohol and disintegrant are first
combined and then that composition is contacted with an aqueous solution of
the film-forming sugar alcohol, albeit at separate concentrations in the
multistage spraying process.
Similarly to the fluidized bed and spray tower processes, in the paddle
dryer process, the Specification teaches that "an initial charge of materials"
( as a fluidizing mixture of non-film-forming sugar or sugar alcohol and
cross-linked PVP) is sprayed with a solution of the film-forming sugar or
sugar alcohol in water and then dried. (Spec. 12:27-28.)
And finally, granulation formulation in "a mixer by means of a
continuously operated mixing aggregation" is described. (Spec. 12:31-
13:3.) In that process, the solid starting materials ("the fine non-film-
forming sugar or sugar alcohol crystals and the particles of crosslinked
PVP") are intensively mixed with the granulating liquid comprising the film-
forming sugar alcohol. (Spec. 12:31-13: 11.)
In short, in each described process, the non-film-forming sugar
alcohol (e.g., mannitol) and disintegrant are put in contact with each other
6
Appeal2017-000602
Application 13/416,558
prior to or at the same time as the addition of the aqueous solution of the
film-forming sugar alcohol ( e.g., sorbitol). This is a different process than
that described by Norman, as will be discussed below.
Norman is directed at providing a tablet that can be processed in high
speed tableting machines that has low friability and sufficient hardness but
that has rapid disintegration or dissolving properties. (Norman 9:30-10: 18.)
Norman explains that a co-processed carbohydrate system is part of that
formulation and it "include[ s] a co-processed carbohydrate plus a
disintegrant and a glidant." (Norman 9:25-26.) Norman indicates that it is
thought that the "co-processed carbohydrate is the ingredient of the
formulation that provides compactibility of the composition" whereas the
disintegrating agent of the dosage form "aids in achieving maximal rapid
disintegration." (Id. at 9:23-25).
As Appellants' explain, Norman teaches that a co-processed
carbohydrate according to its invention is where at least two polyols 5 are
processed "together to make a single product." (Norman 9:21-24; Appeal
Br. 7.) Norman explains different manners of achieving the co-processed
carbohydrates. The list includes co-granulating (a) two or more granular
pol yo ls, or (b) two spray-dried pol yo ls, or ( c) a granular polyol and a spray-
dried polyol. (Norman 10:28-31.) Also included in the list is co-spray
drying at least two polyols. (Id. at 10:31-32; see also id. at 15:31-33).)
Norman teaches that the carbohydrates that can be co-processed include
mannitol and sorbitol. (Id. at 11: 1-10.)
5 Sugar alcohols, such as sorbitol and mannitol, are polyols. (Spec. 2:9-10.)
7
Appeal2017-000602
Application 13/416,558
Norman describes preparation of the co-processed carbohydrate
system as combining a co-processed carbohydrate with disintegrant and
glidant. (See e.g., Id. at 11-13, see also id. at 3--4) When read in its
entirety, it is clear that Norman describes the co-processed carbohydrate
system as being created by first forming the co-processed polyol
composition and then adding to that co-processed polyol additional
ingredients, such as disintegrant. (Id. at 7: 16-29 (noting Figure 11 is a
graph depicting in-vivo disintegration times for co-spray dried
mannitol:sorbitol mixtures seeded with dry blends of mannitol:sorbitol in the
same ratio at varying feed rates, and optionally, followed by a dilution of the
co-spray dried polyol product with Manno gem EZ and Polyplasdone ); id. at
11-13 ( describing preparation of a co-processed carbohydrate system
formulation with mannitol and sorbitol being the polyols to make the co-
processed polyol composition using a co-spray drying process and then
diluting that co-processed polyol with a "co-granulated blend of mannitol
and a disintegrant"); id. at 31-32 ("Example 7: Dilution of the Co-Processed
Product with MANNOGEM EZâ„¢ and POL YPLASDONE XLâ„¢"
describing after the co-spray drying process that the formulations were
diluted with Mannogem and Polyplasdone).)
Norman cannot be fairly read, as the Examiner contends (Ans. 4
(citing Norman pages 11-12 discussing the use of "spray drying
equipment")), to disclose or suggest that the co-processed carbohydrate
system is "agglomerated" with the spray drying equipment. Rather, Norman
simply explains (referring to the flow diagram depicted in Figure 6) that the
spray dryer can be used in a process of making the co-processed
carbohydrate system to both dry the co-polyol solution and to agglomerate
8
Appeal2017-000602
Application 13/416,558
that co-polyol. In particular, Norman states that a "prepared mannitol
powder and sorbitol powder dissolved in hot water" is first made (Norman
11:18-20) and then it is explained "[a]t this point, the polyol composition is
spray-dried" (Id. at 11:29). It is noted that "[a]ny spray dryer" can be used
for so drying the polyol composition, and that is the spray dryer's main use,
but indicating that the spray drying "equipment can also be used for
agglomerating ... the [polyol] composition." (Id. at 11:29-12:4.)
Norman then proceeds to explain with reference to Figure 6 how the
spray dryer is used for both agglomerating the co-polyol and drying it. (Id.
at 12:3--4.) It is explained that the co-polyol enters the top of the spray dryer
(4) where the liquid feed of the polyol from feed line (3) is sprayed via an
atomizer in fine droplets into a hot air stream that enters the top of the dryer
through hot air duct (8) "caus[ing] rapid drying due to the large liquid area
exposed." (Id. at 12:5-12 and Figure 6.) The agglomeration of the co-
polyol takes place in the wet zone (11 ), where co-polyol fines have been
recycled back to the top of the spray dryer where the co-polyol feed enters
the spray dryer. (Id. at 12:13-19.) The agglomerated co-polyol enters "the
integrated fluid bed 1 O" which is fed with hot air where it is dried and when
the desired particle size is achieved, the co-polyol product is collected. (Id.
at 12: 17-29.) Thus, Norman's reference to the use of the spray drying
equipment for agglomerating the composition of "the present invention" is
clearly an indication only that the spray-drying equipment both dries the co-
polyol solution that was fed into it, as well as agglomerating that co-polyol.
The use of spray drying is not mentioned in the production of the co-
processed carbohydrate system that is made by the addition of disintegrant to
the dried co-polyol particle having the desired ratio of polyols and being of a
9
Appeal2017-000602
Application 13/416,558
particularly desired size. Instead, Norman describes formation of that
system as being made by dry blending the ingredients in a Mixer. (See, e.g.,
Norman 20-21 (Formulation Band C).)
In short, Norman's process that involves first obtaining a co-polyol
(by either co-granulation or co-spray drying) wherein the co-polyol is dried
then adding a disintegrant to that dried agglomerated co-polyol is not the
same or similar to the process described in the present Specification to
obtain granules of agglomerated non-film forming sugar alcohol, film-
forming alcohol, and disintegrant. The process described in the present
Specification that achieves the claimed product6 involves combining a liquid
sorbitol as the granulating fluid with a mannitol and disintegrant to form
agglomerates of all three components in the granule.
Moreover, Norman teaches that the co-polyol is a single product
(Norman 9:21-22 ("The term 'co-processed carbohydrate' means the
processing of at least two polyols together to make a single product"), as
indicated by Appellants (Appeal Br. 8-9). There is nothing in Norman to
suggest that when that single co-polyol product is combined with the
disintegrant as described in Norman, i.e., through dilution by dry-blending
an agglomerated dried mannitol/sorbitol co-polyol product with a
disintegrant, that a granule is formed that contains mannitol, sorbitol, and
disintegrant as an agglomerate. Nor has the Examiner pointed to anything in
6 We note that, contrary to Appellants' position (Appeal Br. 8), the
composition of claim 1 does not require "one or more water insoluble, film-
forming polymers, and one or more pharmaceutically customary auxiliaries"
because these named ingredients may be present in the composition at 0%.
(Appeal Br. Claims Appendix (claim 1).)
10
Appeal2017-000602
Application 13/416,558
the art that would indicate such an agglomerated composition would be an
inherent result. The issue is not, as the Examiner indicates (Final Action 2-
3), whether "[ a ]dding of a disint[ e ]grant has not been show[ n] to prevent the
agglomerate even if added after the fact," but whether Norman would be
understood to teach or suggest that the disintegrant, when added to the
agglomerated co-pol yo 1, would result in an agglomerate of the disintegrant
with the co-polyol. We find the Examiner's evidence lacking in this regard.
Contrary to the Examiner's assertion (Non-final 2013 at 3), Norman
does not teach the co-polyol agglomerate plus disintegrant forms a particle
in a particular size range. Rather, Norman teaches that in the spray-drying
process where the solution of a film-forming and non-film forming
carbohydrate is fed into a spray-dryer, agglomeration of those carbohydrates
takes place and the desired co-polyol particle size is achieved in the drying
chamber. (Norman 11 :7-12:31.) That agglomerated co-polyol particle is
what is later combined with a disintegrant. (Norman 13:4--19.) The
Examiner did not establish an evidentiary basis that would indicate that the
combined co-polyol with disintegrant would form a new agglomerate that
includes the disintegrant with the co-polyol, rather than, providing a
composition of individual co-polyol particles with disintegrant particles.
It is true, as the Examiner notes (Final Action 3), that Norman teaches
the co-processed carbohydrate system is superior over the dry-blend of
ingredients of two separate polyols plus disintegrant and glidant. (Norman
23:3-5.) However, this does not confirm that the addition of disintegrant to
the co-polyol results in an agglomerate of the co-polyol and disintegrant.
The comparison does not address what form the composition that includes
the co-polyol and disintegrant take on at all. Norman notes the superiority
11
Appeal2017-000602
Application 13/416,558
of the co-processed carbohydrate system in a comparison of (1) a co-
processed mannitol:sorbitol composition (Formulations A and D)7 that is
blended together with (a) a disintegrant and (b) a glidant and then tableted
after being dry blended with an active pharmaceutical agent and other
pharmaceutically customary auxiliaries to (2) a composition in which spray
dried mannitol (80% of total formulation) is dry-blended with (a) granular
sorbitol (10% of total formulation) or a spray-dried sorbitol (10% of total
formulation), (b) a disintegrant, and ( c) a glidant (Formulations B and C,
respectively) and then tableted after being dry blended with active
pharmaceutical agents and other pharmaceutically customary auxiliaries.
(Norman 19--22.)8 That comparison does not demonstrate anything with
respect to whether the disintegrant added after the agglomerated co-polyol
particles are formed results in an agglomerated disintegrant and co-polyol.
It simply demonstrates that an agglomerated co-polyol plus disintegrant and
glidant results in a tablet that has superior hardness compared to a tablet that
7 Formulation A is a mannitol:sorbitol co-polyol in a 90: 10 ratio and
formulation Dis a mannitol:sorbitol co-polyol in a ratio of 80:20.
8 While not mentioned by the Examiner, we note that Formulations Band C
of Norman include the claimed ingredients in the claimed amounts.
However, the ingredients, which were all dried particles were "dry-blended"
to obtain the formulation. (Norman 20:15-20, 21:2-7.) The Specification
explains that the agglomerated granules are formed through a very different
process as discussed in detail above. In particular, it is explained that an
aqueous solution of the film-forming sugar alcohol is added to solid particles
of the non-film-forming sugar alcohol and the disintegrant or to a solution of
non-film-forming sugar alcohol plus a disintegrant. Consequently, we do
not understand Formulations Band C to form granules of an agglomerated
film-forming sorbitol, non-film forming mannitol, and disintegrant as
required by the claims.
12
Appeal2017-000602
Application 13/416,558
was made by dry blending a composition of the same two polyols but added
as separate particles that also had the same glidant and disintegrant added.
(Norman 22-23.)
"[T]he [E]xaminer bears the initial burden, on review of the prior art
or on any other ground, of presenting a prima facie case of unpatentability."
In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992). In light of the above
discussion, we determine that the Examiner has failed to establish a prima
facie case that the co-processed carbohydrate system described in Norman
includes granules comprising agglomerates of a disintegrant, a non-film
forming sugar alcohol, together with a film-forming sugar alcohol.
Consequently, we do not sustain the Examiner's rejection of claims 1-13
under 35 U.S.C. § 102(b) as being anticipated by Norman.
SUMMARY
We reverse the rejection of claims 1-13 under 35 U.S.C. § 102(b) as
being anticipated by Norman.
REVERSED
13