Samyang Biopharmaceuticals Corporation

Patent Trials and Appeals Board

Jun 23, 2020

2019006487 (P.T.A.B. Jun. 23, 2020)

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.
14/556,510 12/01/2014 Ho-Jin Chung LPP20144631US 2606
66390 7590 06/23/2020
LEX IP MEISTER, PLLC
5180 PARKSTONE DRIVE, SUITE 175
CHANTILLY, VA 20151
EXAMINER
PURDY, KYLE A
ART UNIT PAPER NUMBER
1611
MAIL DATE DELIVERY MODE
06/23/2020 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
__________

Ex parte HO-JIN CHUNG, SANG-YEOB PARK, and
CHAUL-MIN PAI
__________

Appeal 2019-006487
Application1 14/556,510
Technology Center 1600
__________

Before FRANCISCO C. PRATS, ULRIKE W. JENKS, and
RACHEL H. TOWNSEND, Administrative Patent Judges.

TOWNSEND, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims to a
method for controlling tamsulosin release, which have been rejected as
obvious. We have jurisdiction under 35 U.S.C. § 6(b).
We affirm.
STATEMENT OF THE CASE
Tamsulosin is an α1 blocker that is known to be effective in oral
dosage form in treating “dysuria due to benign prostate hyperplasia.” (Spec.
1.) It “is administered in a small dose because of its very strong efficacy”

1 We use the word “Appellant” to refer to “applicant” as defined in 37
C.F.R. § 1.42. Appellant identifies the real party in interest as SAMYANG
BIOPHARMACEUTICALS. (Appeal Br. 2.)
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and it is known to have “very fast absorption in vivo.” (Id.) The
Specification explains that “if the initial blood concentration of tamsulosin is
excessively increased . . . side-effects such as orthostatic hypotension and so
on may occur despite high selectivity [of tamsulosin] to the prostatic smooth
muscle” and thus the “preferred dosage form of tamsulosin is a delayed and
sustained release type of controlled-release preparation.” (Id. at 1–2.)
Appellant’s invention “relates to a controlled-release pharmaceutical
composition [of] tamsulosin.” (Id. at 1.)
Claims 21–28 and 30–32 are on appeal. Claim 21 is representative
and reads as follows:
21. A method for controlling tamsulosin release so that upon
oral administration, 30% or less of tamsulosin is released for 2
hours and the rest of tamsulosin is gradually released for 6
hours or longer, which comprises:
administering a pharmaceutical composition which
comprises a first group of microparticles and a second group of
microparticles, each of the microparticles comprising:
a core comprising tamsulosin or pharmaceutically
acceptable salts thereof;
a controlled-release polymer coating layer formed on the
core; and
an enteric polymer outer layer formed on the controlled-
release polymer coating layer,
wherein an average thickness of the controlled-release
polymer coating layer is different between the first group of
microparticles and the second group of microparticles,
said controlled-release polymer coating layer comprises a
water-insoluble polymer an ethyl acrylate/methyl
methacrylate/trimethylammonioethyl methacrylate chloride
copolymer,
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said enteric polymer outer layer comprises methacrylic
acid/ethyl acrylate copolymer;
wherein said first group of microparticles has an average
thickness of the controlled-release polymer coating layer of 1-
20 μm, and
wherein an average thickness ratio of the controlled-
release polymer coating layer in the first group of
microparticles and the second group of microparticles is 1:1.2-
10,
a weight ratio of the first group of microparticles and the
second group of microparticles is adjusted so that a total weight
ratio of tamsulosin or pharmaceutically acceptable salts thereof
comprised in the first group of microparticles and the second
group of microparticles falls in a range of 1:0.1-4,
the controlled-release polymer coating layer of each of
the groups of microparticles has a same polymer composition;
and
said core is formed by mixing tamsulosin or
pharmaceutically acceptable salts thereof with an inert seed, or
by incorporating tamsulosin or pharmaceutically acceptable
salts thereof in the inert seed, and
wherein the pharmaceutical composition has a
dissolution pattern in which, according to a dissolution test
method of Korean Pharmacopoeia 8th revision (KP VIII) (a
second paddle method: 100 rotations per min, 500 ml of
dissolution solutions at pH 1.2 and pH 7.2):
a) with respect to a dissolution solution at pH 1.2, the
tamsulosin or pharmaceutically acceptable salts thereof are
dissolved in an amount of 1-30 wt% within 2 h, based on a total
weight thereof; and
b) with respect to a dissolution solution at pH 7.2, the
tamsulosin or pharmaceutically acceptable salts thereof are
dissolved in an amount of 10-60 wt% within 30 min, 30-80
wt% within 1 h, and 50 wt% or more within 4 h, based on the
total weight thereof.
(Appeal Br. 11–12.)
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The prior art relied upon by the Examiner is:
Name Reference Date
Shinoda et al. US 7,255,876 B2 Aug. 14, 2007
Speirs et al. US 2006/0127484 A1 June 15, 2006

The following ground of rejection by the Examiner is before us on
review:
Claims 21–28 and 30–32 under 35 U.S.C. § 103(a) as unpatentable
over Shinoda and Speirs.
DISCUSSION
The Examiner finds that Shinoda teaches a composition that
comprises sustained release particles of an active ingredient such as
tamsulosin. (Final Action 3.) The sustained release particles include a
sustained release coating layer that includes an ethyl-acrylate-methyl
methacrylate-trimethyl ammonium chloride ethyl methacrylate copolymer
and an outer enteric coating that may include methacrylic acid/ethyl acrylate
copolymer. (Id. at 3–4.) The Examiner recognizes that Shinoda does not
teach two sets of particles where each set possesses a different controlled-
release coating thickness from the other. (Id. at 4.) However, the Examiner
concludes that such would have been obvious from the teachings of Speirs.
(Id.)
In particular, the Examiner finds that “Sp[ei]rs teaches dosage forms,
similar in structure to Shinoda.” (Ans. 7.) However, explains the Examiner,
Speirs teaches a composition that has two or more sets of plurality of
particles coated with a controlled release layer that can be polymethacrylate.
(Final Action 4; Ans. 8.) The Examiner explains that Speirs teaches that by
“providing different thicknesses [of controlled release layer] on particles of
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drug” in each of a different set of particles, “the drug is released at different
locations in the intestinal tract.” (Final Action 4; Ans. 7 (citing Speirs ¶ 48
and claim 4).) The Examiner further explains that Speirs teaches the
provision of a plurality of particles with varied controlled layer thickness
provides for “targeted rel[e]ase of the drugs to parts of the intestine where
absorption would be most desired (see [0046] and Figure 6)” and a
homogeneous release profile avoiding “underdo[s]ing, overdosing or dose-
dumping” that is what occurs with “conventional controlled release dosage
forms provid[ing] release of the active agent in a time of pH-dependent
manner.” (Ans. 7.) The Examiner further explains that Speirs teaches the
coating thickness is in the range of 5% to 30%. (Final Action 4.)
The Examiner concludes that one of ordinary skill in the art “would
have been motivated to modify Shinoda such that the tamsulosin particles
were provided with controlled release coatings of different thicknesses so as
to provide a user thereof a true, sustained release of drug as the particles
transit the intestinal tract.” (Id.) The Examiner finds “that one ordinarily
skilled in the art would be able to identify useful thickness ratios of the
enteric coating so as to provide the best drug release profile.” (Id. at 5.) The
Examiner further finds with respect to the claimed weight ratio of the first
group of microparticles to the second group of microparticles such that “a
total weight ratio of tamsulosin or pharmaceutically acceptable salts thereof
comprised in the first group of microparticles and the second group of
microparticles falls in a range of 1:0.1–4,” that such “would also be within
the scope of an ordinary skilled person. At the very least, one would
envisage equal amounts of tamsulosin in the particles.”(Id.) The Examiner
explains that “[t]he modification of Shinoda by that of Sp[ei]rs is nothing
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more than providing a known technique (i.e. providing different controlled
release thickness layers) to improve (e.g. provide a targeted homogenous
drug release profile) similar products (see Shinoda) in the same way. See
MPEP 2143(I)(C).” (Ans. 7–8.)
Regarding the preamble of “controlling tamsulosin release such that
30% or less is released for 2 hours and the rest is released gradually for 6
hours,” the Examiner notes that Shinoda’s dosage forms provide “a very
similar outcome” and is a result-effective variable “identified by Shinoda as
a desired variable to optimize.” (Id. at 8–10.)
We conclude that the claimed invention would have been prima facie
obvious from the teachings of Shinoda and Speirs. We agree with the
Examiner that Speirs teaches particle formulations very similar in structure
to those described in Shinoda. (Speirs abstract.) Further, we agree with the
Examiner that Speirs teaches by varying the controlled release coating
thickness of particles, one can control the rate of release of the active
ingredient “in relation to variations in pH of transit through the intestine,
without being solely dependent upon either a specific pH being reached or a
specific time having elapsed before release of the active compound” and/or
can achieve release of the compound at various locations in the intestinal
tract. (Id. ¶¶ 41–49.) Speirs explains with respect to the different thickness
of coating on the two or more sets of particles:
The coating on the particles may be of a thickness
corresponding to a theoretical weight gain on coating of 15%
for one of the pluralities and 20% weight gain for the other and
preferably the number of particles in each plurality are present
as a ratio of 15% weight gain coated particles to 20% weight
gain coated particles of 1:3.
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(Id. ¶ 49.) This difference of weight gain by the particle where the same
coating is used is an indication that the coating layer is thicker on one set of
particles. Moreover, the ratio of “number of particles in each plurality”
being 1:3 will inherently result in a total weight of active being different in
the two sets of particle. Indeed, the ratio would appear to meet Appellant’s
claimed ratio range of between 1:0.1–4.
As the Examiner finds, and Appellant does not dispute, Shinoda
describes the desire to have a sustained-release composition of tamsulosin
where the active compound is in the core of particle that is coated with the
claimed sustained-release coating and which coating is further covered by an
enteric coating.
We agree with the Examiner that it would have been obvious to one of
ordinary skill in the art to have combined the teachings of Speirs with
Shinoda to have arrived at a composition of tamsulosin that would have
controlled release along the intestinal tract where the composition included
at least two different sets of particles with a different thickness of the same
controlled-release layer, which composition would have had the weight ratio
of tamsulosin in the sets of particles claimed. Appellant argues the
Examiner’s rejection is in error because “there is no teaching or suggestion
in the art for one of ordinary skilled person to adjust the weight ratio of the
first group of microparticles and second group of microparticles as claimed.”
(Appeal Br. 8.) For the reasons just discussed, we do not find this argument
persuasive.
Moreover, we note that in Appellant’s Appeal Brief section entitled
Summary of the Claimed Subject Matter, which section is supposed to
provide “[a] concise explanation of the subject matter defined in each of the
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rejected independent claims, which shall refer to the specification in the
Record by page and line number or by paragraph number, and to the
drawing, if any, by reference characters” (37 C.F.R. § 41.37) (emphasis
added), does not direct our attention to what in particular is meant by this
limitation. We note that as the controlled release layer thickness increases
the weight of tamsulosin per weight of the particle will change: i.e., the
thicker the particle, the lower the weight percentage of tamsulosin per
weight of particle. Although not entirely clear, the Specification seems to
suggest that the weight ratio change may be provided simply by the change
in the coating thickness or by adjusting the amount of active ingredient in
the particle or by adjusting the number of particles in the various coating
thickness groups (Spec. 15–16), and Appellant does not provide any other
explanation. As noted above, Speirs teaches in one case, a 5% difference in
weight gain for particle groups where the number of particles per group is
1:3. (Speirs ¶ 49.) However, Speirs also teaches the coating thicknesses of
the two groups can be anywhere from 5% to 30% (id. ¶ 76) and notes that
the number of particles in each group can be varied (id. ¶ 46), and thus,
recognizes these are both results-effective variables depending on the control
one desires over the release of the active ingredient. We conclude that in
whatever way one interprets the weight ratio limitation, it is a known results-
effective variable. But, even if it is determined that paragraph 49 of Speirs
does not specifically teach an embodiment within the claimed weight ratio,
we note that “discovery of an optimum value of a result effective variable in
a known process is ordinarily within the skill of the art.” In re Boesch, 617
F.2d 272, 276 (CCPA 1980); In re Aller, 220 F.2d 454, 456 (CCPA 1955)
(“[W]here the general conditions of a claim are disclosed in the prior art, it is
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not inventive to discover the optimum or workable ranges by routine
experimentation.”)
Appellant explains that “excessive release at early stage could be
prevented, as well as initial efficacy manifestation” is achieved by the
claimed weight ratio in the different particle groups “so that upon oral
administration, 30% or less of tamsulosin is released for 2 hours and the rest
of tamsulosin is gradually released for 6 hours or longer” as required by the
preamble of claim 21 and that such an effect is not taught or suggested by
the references. (Id. at 8–9.) We do not find this argument persuasive as the
weight ratio and coating thickness limitations are taught to be result effective
in the control of the release of active ingredient to achieve homogeneity of
release by Speirs. Furthermore, as just discussed, we find the weight ratio
claimed by Appellant to be taught by Speirs and there is no dispute that the
average thickness ratio of the controlled-release layer is taught by Speirs.
Consequently, because the structure of the particles is taught by Speirs, and
we find that it would have been obvious to provide tamsulosin as the active
ingredient in a composition that has these particles, we conclude that the
controlled-release rate required by the claimed structure would have been
met. “It is a general rule that merely discovering and claiming a new benefit
of an old process cannot render the process again patentable.” In re
Woodruff, 919 F.2d 1575, 1578 (Fed. Cir. 1990). Although the claimed
process is not entirely old, in that Speirs does not anticipate because
tamsulosin is not taught to be the active ingredient included in a particulate
composition that has two or more sets of particulates having different
thicknesses of the controlled-release polymer, “the rule is applicable here to
the extent that the claims and the prior art overlap.” Id. It is of no
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consequence that this characteristic of the particulate composition was not
recognized by the prior art. See, e.g., Perricone v. Medicis Pharm. Corp.,
432 F.3d 1368, 1378 (Fed. Cir. 2005).
Appellant argues further that the prior art does not teach the ratio
requirements of claim 23. (Appeal Br. 9.) However, we find that Speirs
teaches that there can be “two or more pluralities of active compound
containing particles coated with a desired thickness of a polymethacrylate
material . . . to control the release profile of the active compound” and use of
differing coating thickness on these particles to control the release profile
through the intestinal tract. (Speirs ¶ 2.) Given that Speirs also teaches one
weight ratio range to be 1:3, and provides that the weight ratio is a result-
effective variable in achieving controlled release, we conclude that it would
have been obvious to one of ordinary skill in the art to optimize a ratio
within the broadly claimed range of 1:01.–4:0.1–10. In re Boesch, 617 F.2d
at 276; In re Aller, 220 F.2d at 456.
Thus, for the reasons discussed, we affirm the Examiner’s rejection of
claims 21 and 23 as being obvious from Shinoda and Speirs.
Claims 22, 24–28 and 30–32 have not been argued separately and,
therefore, fall with claim 21. 37 C.F.R. § 41.37(c)(1)(iv).

DECISION SUMMARY
In summary:
Claims
Rejected
35 U.S.C.
§
Reference(s)/Basis Affirmed Reversed
21–28, 30–
32
103(a) Shinoda, Speirs 21–28, 30–
32

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TIME PERIOD FOR RESPONSE
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a). See 37 C.F.R.
§ 1.136(a)(1)(iv).
AFFIRMED