Ex Parte 6024981 et al

Patent Trial and Appeal Board

Nov 8, 2013

90008133 (P.T.A.B. Nov. 8, 2013)

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
www.uspto.gov
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
90/008,133 09/07/2006 6024981 15514/40037 9856
21832 7590 11/08/2013
MCCARTER & ENGLISH, LLP HARTFORD
CITYPLACE I
185 ASYLUM STREET
HARTFORD, CT 06103
EXAMINER
HUANG, EVELYN MEI
ART UNIT PAPER NUMBER
3991
MAIL DATE DELIVERY MODE
11/08/2013 PAPER
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.
PTOL-90A (Rev. 04/07)
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
www.uspto.gov
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
90/007,684 08/22/2005 6024981 15514/40037 1442
21832 7590 11/08/2013
MCCARTER & ENGLISH, LLP HARTFORD
CITYPLACE I
185 ASYLUM STREET
HARTFORD, CT 06103
EXAMINER
HUANG, EVELYN MEI
ART UNIT PAPER NUMBER
3991
MAIL DATE DELIVERY MODE
11/08/2013 PAPER
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.
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

CIMA LABORATORIES, INC.
Patent Owner and Appellant
____________

Appeal 2013-006904
Reexamination Control Nos. 90/007,684 and 90/008,133
Patent 6,042,981
Technology Center 3900
____________

Before ROMULO H. DELMENDO, SALLY GARDNER LANE,
RICHARD M. LEBOVITZ, Administrative Patent Judges.

LEBOVITZ, Administrative Patent Judge.

DECISION ON APPEAL
In the March 24, 2011 Board of Patent Appeals and Interferences1
Decision on Rehearing (“the ‘3071 Reh’g Dec.”), the Board entered three
new rejections (‘3071 Reh’g Dec. 10-11). The Examiner has maintained
two of those rejections as summarized below. Upon reconsideration of the
appeal record including new evidence, we reverse the Examiner and

1 The Board of Patent Appeals and Interferences became the Patent Trial and
Appeal Board on September 16, 2012.
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withdraw the remaining two rejections.
Currently, claims 1-82 are pending in the application. Claims 66-77
have been withdrawn. Claims 37-40 are not rejected. Claims 1-36, 41-65
and 78-82 stand rejected by the Examiner and are under Appeal. The
rejections are as follows:
1. Claims 1-36, 41-65 and 78-82 under 35 U.S.C. § 103(a) as obvious
in view Alkire2 and Banker3 as evidenced by Kanig4 (‘3071 Reh’g Dec. 8).
2. Claims 1-36, 41-63 and 78-82 under 35 U.S.C. § 103(a) as obvious
in view of Wehling5 and Banker as evidenced by Alkire and Kanig (‘3071
Reh’g Dec. 8).
Independent claim 1 is representative and reads as follows:
l. A hard, compressed, rapidly dissolvable dosage form adapted
for direct oral dosing comprising: an active ingredient and a
matrix including a non-direct compression filler, and a
lubricant, said dosage form being adapted to rapidly dissolve in
the mouth of a patient and thereby liberate said active
ingredient, and having a friability of about 2% or less when
tested according to the U.S.P., said dosage form having a
hardness of at least about 15 Newtons.
Both Rejections 1 and 2 are based on the teachings in Alkire and
Wehling of a hard compressed dosage form comprising mannitol. In both
patents, the same example (Alkire, Table A at col. 10, ll. 45-53; Wehling,
Table 1 at col. 10, ll. 23-29) is disclosed of a tableting mixture comprising

2 U.S. Patent 5,607,697 issued March 4, 1997.
3 Gilbert S. Banker, Garnet E. Peck and George Baley, “Tablet Formulation
and Design” in Pharmaceutical Dosage Forms: Tablets Vol. 1, 61-80
(Herbert A. Lieberman and Leon Lachman, eds., 2d ed. 1980).
4 J.L. Kanig, “Properties of Fused Mannitol in Compressed Tablets,” 53 J.
Pharm. Sci. 2 188-192 (1964).
5 U.S. Patent 5,178,878 issued January 12, 1993.
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“Mannitol” to make a tablet, without describing whether the mannitol is a
direct or non-direct compression filler (‘3071 Reh’g Dec. 8-9). Mannitol
can be in either direct compression form in which the mannitol is modified
to improve its flow characteristics or in an unmodified, non-direct
compression form (NDCF). Based on the evidence, including the Banker
publication, it was determined in the Rehearing Decision that the recited
“mannitol” was one which had not been modified prior to compression and
therefore met the definition of a non-direct compression filler (id. at 9-10;
Decision on Appeal, dated September 28, 2009, defining “non-direct
compression filler” on page 18).
To rebut this conclusion, Patent Owner provided a declaration by
Robert O. Williams III, Ph.D. (Supplemental Williams Declaration dated
February 3, 2012 (“Suppl. Williams Decl.”). Dr. Williams has a Ph.D. in
Pharmaceutics and testified that he has extensive experience in
pharmaceutical formulation (Suppl. Williams Decl. ¶¶ 2-3). We find that
Dr. Williams is qualified to testify as to the matters in his declaration
concerning the claimed tablet formulations.

REJECTION 1 BASED ON ALKIRE
Dr. Williams testified in his declaration that a “person of skill in the
art of pharmacy or pharmaceutical formulation at the time of the invention
would understand the term ‘non-direct compression filler’ (‘NDCF’) to
mean a filler that, without physical modification, does not demonstrate
adequate flow and compression characteristics to allow it to be used in direct
compression processes and products.” (Suppl. Williams Decl., p. 6, ¶ 14.)
Dr. Williams testified that, contrary to the Board’s finding in the ‘3071
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Decision, neither Banker nor Alkire described a direct compression tablet
made with a non-direct compression filler. Rather, Dr. Williams stated that
the person of skill in the art at the time of the invention reading Alkire would
have concluded that Alkire used a modified direct compression form of
mannitol (Suppl. Williams Decl., p. 11-12, ¶ 32). Dr. Williams based his
opinion on several lines of evidence:
First, evidence that the mannitol used in Alkire was deagglomerated
and granulated prior to use (Suppl. Williams Decl. ¶ 31; Alkire, col. 15, ll.
33-40; see “1. Alkire” supra.).
Second, evidence in prior art publications that mannitol cannot be
directly compressed unless it is modified by, e.g., granulation or
agglomeration (Suppl. Williams Decl. ¶ 38; see “2. Prior art teachings on
mannitol” supra.).
Third, evidence that Banker’s “[m]annitol formulation” is a granular
modified mannitol, because granular mannitol require lubricants and glidants
(Suppl. Williams Decl. ¶ 35; see “3. Banker” supra.).
Based on this evidence, Dr. Williams testified that although Alkire
was silent on the processing steps performed on the mannitol listed in Table
A and Example V of Alkire, the skilled worker would have concluded that
the mannitol was granulated (Suppl. Williams Decl. ¶ 32). Similar
testimony applies to Wehling.

1. Alkire
Dr. Williams testified that the “person of skill in the art at the time of
the invention reading Alkire would have concluded that Alkire used a direct
compression form of mannitol.” (Williams Decl. ¶ 31.) In support of this
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opinion, Dr. Williams cited Alkire’s express teaching that mannitol required
deagglomeration.
Mannitol comprises 100% of the material that is initially
charged into the fluidized bed for the granulation process. As
received from the vendor, the mannitol has a tendency to
compact and form agglomerates during shipment. To eliminate
these agglomerates, a deagglomeration procedure was
implemented. The deagglomeration process involves passing
the mannitol through a Frewitt® oscillating granulator equipped
with a US No. 20 screen. Sufficient mannitol was
deagglomerated to generate eight batches of granulated
material.
(Alkire, col. 15, ll. 28-38.)
As indicated in the disclosure referred by Dr. Williams, the mannitol
“received from the vendor” is deagglomerated to produce a “granulated
material.” Such material would not be a NDCF, because it had been
modified prior to tablet compaction. Although Alkire does not state that the
mannitol utilized in Table A and Example V was such “granulated material,”
it is logical that the aforementioned procedure was used for all mannitol
utilized in the Alkire patent, because of its compaction during shipment.

2. Prior art teachings on mannitol
Dr. Williams cited several publications, published prior to the patent’s
filing date, which he contends establish “that when a direct compression
method was performed, the mannitol filler material must have either been
granulated in order to improve its flow and compression or a DCF [direct
compression form] version of mannitol was used” (Williams Decl. ¶ 32).
The most pertinent of those teachings are reproduced below:

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(a)
Mannitol is widely used in the form of a powder which is wet
granulated, but it is also available in granular form which can
be used in direct compression.
(Sheth (1980),6 p. 158; Suppl. Williams Decl. ¶ 36.)
(b)
Mannitol is commonly used in tablets prepared by the wet
granulation process.
. . . .
Because of its poor flowability and binding properties,
unmodified mannitol cannot be used for tablet production by
direct compression. For this reason, the product has been
modified to improve its tableting characteristics. Kanig . . .
prepared a directly compressible mannitol by the spray
congealing of a melt. . . . All modified mannitol products have
excellent flow and compression characteristics.
(Bolhuis and Chowhan7 (1995), p. 458-459 (emphasis added); Williams
Decl. ¶ 36.)
(c)
[M]annitol may be used in direct compression tablet
applications for which the granular form was especially
developed, or wet granulations, which may be readily dried. A
lubricant, such as magnesium stearate 1-2% w/w should be
used in direct compression processes.

6 Bhogi B. Sheth, “Compressed Tablets” in Pharmaceutical Dosage Forms:
Tablets Vol. 1 Herbert A. Leiberman ed.Marcel Dekker, Inc. (1980).
7 Gerad K. Bolhuis and Zak T. Chowhan, “Materials for Direct Compaction”
in Pharmaceutical Powder Compaction Technology, Drugs and the
Pharmaceutical Sciences, Vol. 71. Goran Alderborn and Nystrom Christer,
eds. Marcel Dekker, Inc., 419-500 (1996).
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Wade, 8 p. 294 (footnotes omitted); Williams Decl. ¶ 37. Thus, Wade
expressly teaches that lubricants are used with granulated, modified,
mannitol.
The evidence cited by Dr. Williams supports his testimony that
unmodified, non-direct compression mannitol is not used in tablet
production, but rather is first subjected to wet granulation or incorporated in
a granular form.
3. Banker
Banker was cited in the ‘3071 Rehearing Decision as teaching that
non-direct compression fillers had been used in tablets prior to the filing date
of the ‘981 patent (‘3071 Reh’g Dec. 9). The Decision stated:
However, Banker indicated that unmodified mannitol (i.e.,
nondirect) had been used in the tableting process (FF6 & FF7).
The presence of lubricant and glidant in these examples would
be consistent with unmodified mannitol, since Banker reported
that usually lubricant and glidant were required in greater
amounts to improve the flow properties of this unmodified form
(FF6). Thus, Alkire's disclosure reasonably suggests
incorporating nondirect compression mannitol into the example
shown in Table A.
(‘3071 Reh’g Dec. 9-10; emphasis added.)
Findings of Fact 6 and 7, referenced in the passage above, are based
on the following disclosure from Banker reproduced below:
Mannitol formulations, because of their poor flow properties,
usually require higher lubricant levels (3 to 6 times as great)
and higher glidant levels for satisfactory compression than
other diluents. Kanig . . . has reported on studies to overcome
these shortcomings by spray-congealing fused mannitol alone

8 Ainley Wade and Paul J. Weller, “Mannitol,” in Handbook of
Pharmaceutical Excipients, Am. Pharm. Ass’n 294-98 (2d ed. 1994).
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with sucrose or lactose. A wide range of tablet hardness can be
obtained with mannitol-based tablets. Mannitol is a relatively
expensive diluent, and attempts are usually made to reduce its
quantity per tablet.
(Banker (1980), p. 78.)
Dr. Williams testified that, contrary to the findings and conclusion in
the ‘3071 Decision, Banker does not teach using non-direct compression
fillers in a direct compression tableting process. Dr. Williams stated:
Banker is actually referring to formulations comprising granular
mannitol, such as, e.g., formulations for chewable vitamins,
rather than properties of physically unmodified (i.e., NDCF)
mannitol. It is well known that the flowability of granulated
fillers can vary.
(Williams Decl. ¶ 35.)
First, Dr. Williams asserts, citing facts (a) through (c) above, and prior
art disclosures about the flow characteristics of mannitol, the skilled worker
would have known that mannitol is not used in direct compression, unless is
it modified (Williams Decl. ¶¶ 35-40). In particular, Dr. Williams testified
that because of the poor flowability of unmodified mannitol, the prior art
taught that it was not used for tablet production by direct compression (id. at
¶ 35). Therefore, Dr. Williams contends the disclosure of mannitol tablet
formulations by Banker would not have been understood to be a reference to
unmodified mannitol, but rather to granulated mannitol (id. at ¶ 35), such as
a direct compression granulated form, or a mannitol subjected to a wet
granulation step (id. at ¶¶ 36-37). Dr. Williams’s testimony is factually
supported.
In the Decision, we had stated that Banker’s mention of using glidants
and lubricants in the tablets was consistent with the mannitol being
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unmodified (‘3071 Decision 9-10; reproduced above with bolded emphasis).
However, Dr. Williams provided persuasive evidence that glidants and
lubricants were used in tablets comprising granulated mannitol (Williams
Decl. ¶ 37). For example Dr. Williams quoted from disclosure by Wade on
page 297. The full passage is reproduced below:
Granulated mannitol flows well and imparts improved flow
properties to other materials. However, it usually cannot be
used with concentrations of other materials exceeding 25% by
weight. Recommended levels of lubricant are 1% w/w calcium
stearate or 1-2% w/w/ magnesium stearate. . . . Usually, 3-6
times as much magnesium stearate or 1.5-3 times as much
calcium stearate is needed for lubrication of mannitol
granulations than is needed for other excipients.
(Wade, p. 297, col. 1.)
In view of Dr. Williams’s testimony and evidence, we agree that the
evidence does not support our original finding that Banker’s mention of
using glidants and lubricants in the tablets was consistent with the mannitol
being unmodified.
4. Summary
Based on the evidence and testimony of Dr. Williams, we are
persuaded that a person of ordinary skill in the art would not have
understood the disclosure in Alkire of mannitol used in a tableting process to
have been an unmodified mannitol or to have suggested one. Accordingly,
we withdraw Rejection 1.

REJECTION 2 BASED ON WEHLING
Wehling discloses the same tableting example described in Alkire
which we found to have involved the use of a direct compression mannitol,
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not the non-direct form required by the claims. Consequently, for
substantially the same reasons as for Rejection 1 based on Alkire, we
withdraw Rejection 2 over Wehling and Banker (see also Williams Decl. ¶¶
43-49).

REVERSED

lb
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Patent 6,042,981

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FOR PATENT OWNER:

McCARTER & ENGLISH, LLP
CITYPLACE I
185 ASYLUM STREET
HARTFORD, CT 06103-3495

FOR THIRD PARTY REQUESTER:

ALAN H. NORMAN, ESQ.
THOMPSON COBURN, LLP
ONE US BANK PLAZA
ST. LOUIS, MO 63101