Ex Parte Imboden et al

Patent Trial and Appeal Board

Oct 26, 2016

11997348 (P.T.A.B. Oct. 26, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
111997,348 02/28/2008
126354 7590 10/28/2016
Erickson Kernell IP, LLC
8900 State Line Rd, Suite 500
Leawood, KS 66206
FIRST NAMED INVENTOR
Roger Imboden
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.
3024.24 5576
EXAMINER
BECKHARDT, LYNDSEY MARIE
ART UNIT PAPER NUMBER
1613
NOTIFICATION DATE DELIVERY MODE
10/28/2016 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):
ekdkdocket@kcpatentlaw.com
bvg@kcpatentlaw.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte ROGER IMBODEN,
ERICH ROTHENBUHLER, and JUERG LUTZ
Appeal2015-004126
Application 11/997 ,348
Technology Center 1600
Before DEMETRA J. MILLS, JEFFREY N. FREDMAN, and
RYAN H. FLAX, Administrative Patent Judges.
FREDMAN, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal 1 under 35 U.S.C. § 134 involving a pharmaceutical
composition comprising either indomethacin and/or acemetacin. The
Examiner rejected the claims as indefinite, as being of improper dependent
form, and as obvious. We have jurisdiction under 35 U.S.C. § 6(b ). We
affirm.
1 Appellants identify the Real Party in Interest as the Drossapharm AG (see
Br. 3).
Appeal2015-004126
Application 11/997 ,348
Statement of the Case
Background
"[I]ndomethacin and acemetacin and their preparation are known.
The compounds have anti-inflammatory, pain-relieving and antipyretic
properties" (Spec. 1: 8-9). "[B]oth active ingredients, especially acemetacin,
have a bitter taste, making them unsuitable for peroral administration, e.g. in
the form of an effervescent preparation. Unexpectedly, the bitter taste, e.g. in
an effervescent preparation or a suspension, could not be masked with the
flavorings conventionally used in pharmacy" (Spec. 1: 19-23).
The Specification teaches that "the bitter taste of micronized
indomethacin and acemetacin is efficiently masked by the addition of
flavonoid derivatives" (Spec. 2:23-24).
The Claims
Claims 1-31 are on appeal. 2 Claim 1 is representative and reads as
follows:
1. Pharmaceutically effective composition in a
pharmaceutical form for oral administration containing at least
one of the active ingredients indomethacin and acemetacin and
optionally other additives, characterized in that
(i) this composition contains the active ingredient or a
mixture of these active ingredients in micronized form,
whereby said micronized form has been obtained by
micronization using mechanical means;
(ii) the micronized active ingredient has a particle size
distribution in the range of 0.1 µm (micron) to 1 OOµm (micron);
2 The Examiner denied entry of Appellants' amendment in the Advisory
Action mailed Jan. 17, 2014, which results in claims 1, 2, 4--11, 16, 17, 19-
22, 24, 25, and 28-31 remaining pending and claims 3, 12-15, 18, 23, 26,
and 27 being withdrawn from consideration (see Final Act. 1 and Summary).
2
Appeal2015-004126
Application 11/997 ,348
(iii) said active ingredient in micronized form being
present in the form of microcrystals;
(iv) said composition consisting of the active
ingredient(s) in a mixture with at least one compound selected
from the group consisting of: chalcone[] glycosides and
dihydrochalcone[] glycosides, and combinations thereof.
The Issues
A. The Examiner rejected claims 1, 9, and 10 under 35 U.S.C. § 112,
second paragraph, as indefinite (Ans. 2-3).
B. The Examiner rejected claim 9 under 35 U.S.C. § 112, fourth
paragraph, as failing to further limit the subject matter of a previous claim
(Ans. 3--4).
C. The Examiner rejected claims 1, 2, 4--11, 16, 17, and 28-30 under
35 U.S.C. § 103(a) as obvious over Machoczek, 3 Samejima, 4 and Felisaz5
(Ans. 5-10).
D. The Examiner rejected claims 1, 24, and 25 under 35 U.S.C. § 103(a)
as obvious over Nakamichi, 6 Samejima, and Felisaz (Ans. 10-13).
E. The Examiner rejected claims 1, 2, 4--8, 19-22, 24, 25, and 31 under
35 U.S.C. § 103(a) as obvious over Dell, 7 Samejima, Zerbe, 8 and Felisaz
(Ans. 13-19).
3 Machoczek, H., US 6,066,335, issued May 23, 2000 ("Machoczek").
4 Samejima et al., US 5,202,129, issued Apr. 13, 1993 ("Samejima").
5 Felisaz et al., US 6,599,534 B2, issued July 29, 2003 ("Felisaz").
6 Nakamichi et al., US 5,456,923, issued Oct. 10, 1995 ("Nakamichi").
7 Dell et al., US 4,900,557, issued Feb. 13, 1990 ("Dell").
8 Zerbe et al., US 5,948,430, issued Sept. 7, 1999 ("Zerbe").
3
Appeal2015-004126
Application 11/997 ,348
A. 35US.C.§112, second paragraph
The Examiner finds the "use of open and closed language in the same
claims makes the metes and bound unclear, rending claim 1 indefinite. For
examin[ ation] purposes the claim will be interpreted as open language"
(Ans. 3). The Examiner also finds that "[ c ]laims 9-10 recite[] the limitation
'flavonoid derivatives'[, and t]here is insufficient antecedent basis for this
limitation" (id.).
The issue with respect to this rejection is: Does the evidence of
record support the Examiner's finding that claims 1, 9, and 10 are indefinite?
Findings of Fact
1. Claim 9 recites: "Composition according to claim 1,
characterized in that said flavonoid derivatives being a chalcone glycosides
and/or a dihydrochalcone glycosides" (Br. 44).
Principles of Law
Miyazaki stated that "if a claim is amenable to two or more plausible
claim constructions, the US PTO is justified in requiring the applicant to
more precisely define the metes and bounds of the claimed invention by
holding the claim unpatentable under 35 U.S.C. § 112, second paragraph, as
indefinite." Ex parte Miyazaki, 89 USPQ2d 1207, 1211(BPAI2008).
Analysis
Claim 1
Appellants contend the "language from claim 1, as in the example,
specifies that the composition contain at least one active ingredient, but may
also contain other ingredients. Claim 1 then, using the closed language,
4
Appeal2015-004126
Application 11/997 ,348
limits the active ingredients to chalcone glycosides and/or dihydrochalcone
glycosides" (Br. 15).
We find that the Examiner has the better position. As Zietz notes
"during patent prosecution when claims can be amended, ambiguities should
be recognized, scope and breadth of language explored, and clarification
imposed." In re Zietz, 893 F.2d 319, 321 (Fed. Cir. 1989). Here, the instant
claim 1 is reasonably open to multiple conflicting interpretations.
One interpretation, proposed by Appellants, is that the closed
"consisting of' clause limits the active ingredients to "chalcone glycosides
and/or dihydrochalcone glycosides" (Br. 15). However, this interpretation
might be read to exclude indomethacin and acemetacin as active ingredients,
even though these compounds are expressly recited as "active ingredients."
A second interpretation is that the open "containing" phrase regarding
"active ingredients" permits the inclusion of any active ingredient, and that
the composition must further "consist" of these active ingredients with either
chalcone glycosides and/or dihydrochalcone glycosides.
A third interpretation compares the "optionally other additives"
language in the preamble of claim 1, with no constraint on any chemical
whatsoever functioning as an additive, with the "consisting of' language in
step (iv), and reasons that this language directly conflicts because, as the
Examiner points out, the claim cannot be both "open" and "closed" at the
same time.
A fourth reasonable interpretation is that the "consisting of' clause at
paragraph "iv" limits the claimed pharmaceutically effective composition to
one or both of indomethacin and acemetacin (i.e., the active ingredient(s))
5
Appeal2015-004126
Application 11/997 ,348
and one or both of chalcones glycosides and dihydrochalcones glycosides,
and nothing more. This presents issues with the subsequent depending
claims, which seek to add further components to the limited composition.
In view of the ambiguity present in claim 1, we agree with the
Examiner that claim 1 requires clarification and is reasonably interpreted as
indefinite.
Claims 9 and 10
Appellants do not dispute the Examiner's rejection of claims 9 and 10
for lack of antecedent basis for the term "said flavonoid derivatives," and we
agree that there is no literal basis for this limitation in claim 1. We therefore
agree with the Examiner that claims 9 and 10 are indefinite.
Conclusion of Law
The evidence of record supports the Examiner's finding that claims 1,
9, and 10 are indefinite.
B. 35 USC§ 112,fourth paragraph
We summarily affirm the 35 U.S.C. § 112, fourth paragraph rejection
because no arguments were presented. See MPEP § 1205.02 ("If a ground
of rejection stated by the examiner is not addressed in the appellant's brief,
that ground of rejection will be summarily sustained by the Board.").
C 35 USC§ 103(a) over Machoczek, Samejima, and Felisaz
The Examiner finds that Machoczek teaches "producing effervescent
tablets which consist of at least one active substance or a combination of
6
Appeal2015-004126
Application 11/997 ,348
active substances, of at least one binder, possibly carriers as sweeteners,
flavors ... and include indomethacin" (Ans. 5).
The Examiner acknowledges that Machoczek does not teach "the
indomethacin being micronized" and "does not teach the use of a flavonoid,
particularly the elected neohesperidin dihydrochalcone" (id.).
The Examiner finds that Samejima teaches "a process for micronizing
a slightly-soluble drug ... to produce a micronized drug having an average
diameter of less than about 2-3 mm" and that "[i]ndomethacin is taught as a
micronized drug with 50% average diameter ([µ ]m) of 1.3 and 0.3 5" (Ans.
5-6). The Examiner finds that Felisaz teaches a "masking agent for
pharmaceutical tastes comprising a sapid agent and an enhancer"; that the
agent "can have a grain size comprised between 10 and 100 [µ ]m"; and that
the enhancer may comprise "neohesperidin dihydrochalcone." Id. at 6-7.
The Examiner finds it obvious to "use micronized indomethacin ...
because micronization has long been recognized as a way to solve poor
solubility in gastrointestinal fluids of slightly soluble drugs" and finds it
obvious "to include masking agent including a sweetener and an enhancer to
enhance the sweeten flavor of the sweetener and to hide the parasitic taste of
the sweetener" and "to hide the taste of the pharmaceutical ingredient" (Ans.
6-7).
The issue with respect to this rejection is: Does the evidence of
record support the Examiner's conclusion that the prior art renders claim 1
obvious?
Findings of Fact
7
Appeal2015-004126
Application 11/997 ,348
2. Machoczek teaches "a method of producing effervescent tablets
which consist of at least one active substance or a combination of active
substances, of at least one binder, possibly of carriers as sweeteners,
flavours, colourings, scents, softeners and bleaches" (Machoczek 1:5-10).
3. Machoczek teaches the "active substances to be used in the
method and for the effervescent tablet according to the invention are not
limited at all. They include ... indomethacin" (Machoczek 2: 19-25).
4. Machoczek teaches "flavourings such as sweeteners, sugar
substitutes, flavours or additional or alternate further carriers as colourings
or scents" (Machoczek 2:35-37).
5. Samejima teaches "a process for micronizing a slightly-soluble
drug, which comprises grinding said drug in the presence of a sugar or sugar
alcohol" (Samejima 1: 10-13) and teaches "to improve bioavailability of a
drug through micronization" (Samejima 2:13-14).
6. Samejima teaches that "ultrafine particles of a slightly-soluble
drug, whose average diameter is less than about 2 to 3 µm, preferably less
than 1 µm, can be easily obtained by grinding the drug in the presence of a
grinding aid selected from a sugar and a sugar alcohol by means of a high-
speed stirring mill or impact mill" (Samejima 2:43--49).
7. Samejima teaches "[ s ]pecific examples of the slightly-soluble
drugs are ... anti-inflammatory agents such as indomethacin" (Samejima
2:67 to 3:6).
8. Table 1 of Samejima is reproduced, in part, below:
8
Appeal2015-004126
Application 11/997 ,348
TABLE l
Particle Sizes of Various Compounds
Microniud in the Presence of D·m•nnito1
iffiff" ll . ~iii~x~se Qiameter U!!!)
Before ....... ...Â¥tet Milling
compound Milling alone mixture
indometh:acin 9 1.3 0.35
"Table 1 shows that the particle size of each micronized compound is less
than 1 µm" (Samejima 5:13-14).
9. F elisaz teaches that:
Traditionally, masking agents for unpleasant pharmaceutical
tastes are used whenever the patient, especially a young child,
has to take the medicament orally. The substances used are of
various types and are generally added to the pharmaceutical
formulation as an excipient. For example, we can cite
sweeteners including saccharine and its derivatives.
(Felisaz 1 :22-28).
10. Felisaz teaches "a powdered masking agent for pharmaceutical
tastes in the form of an intimate mixture of a sap id agent and a potentiator"
(Felisaz 2:26-28).
11. Felisaz teaches "[p ]referably, the powdered masking agent
according to the invention has a particle size comprised between 10 and 100
µm" (Felisaz 2:37-39).
12. Felisaz teaches that "[a]s potentiators, one can use ...
glycosides such as neohesperidine dihydrochalcone (NHDC) . . . . These
substances insure a great lingering of the sweet taste and cover the bitter and
metallic aftertaste of saccharine and its salts" (Felisaz 3:7-12).
9
Appeal2015-004126
Application 11/997 ,348
13. F elisaz teaches the "masking agent according to the invention
can be used with a large number of pharmaceutical or therapeutic products
having unpleasant taste, belonging to many different categories thereof, for
example ... antiinflammatory ... agents" (Felisaz 3:48-54).
14. Felisaz teaches, in Example 14, that 95.5% quinine is combined
with 4.6% masking agent, specifically containing "500 mg of quinine
hydrochloride+ 23 .56 mg of masking agent" and that "a sweet and slightly
bitter taste appear at the same time, whereafter the bitter taste disappears
after 3 minutes 45 seconds, whereas the sweet taste is extended until 4
minutes 25 seconds" (Felisaz 7:30-55).
Principles of Law
"The combination of familiar elements according to known methods
is likely to be obvious when it does no more than yield predictable results."
KSR Int 'l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007). "If a person of
ordinary skill can implement a predictable variation, § 103 likely bars its
patentability." Id. at 417. As noted by the Supreme Court in KSR, "[a]
person of ordinary skill is also a person of ordinary creativity, not an
automaton." Id. at 421.
Analysis
We begin with claim interpretation. While we recognize that claim 1
is indefinite as discussed above, "each claim should be reviewed for
compliance with every statutory requirement for patentability in the initial
review of the application, even if one or more claims are found to be
deficient with respect to some statutory requirement" (MPEP § 2103 (I)).
10
Appeal2015-004126
Application 11/997 ,348
We interpret claim 1 for prior art purposes to be consistent with In re
Crish, 393 F.3d 1253, 1257 (Fed. Cir. 2004). Crish found that the
"reasonable interpretation of the claims containing both of the terms
'comprising' and 'consists' is that the term 'consists' limits the 'said
portion' language to the subsequently recited numbered nucleotides, but the
earlier term 'comprising' means that the claim can include that portion plus
other nucleotides." Crish, 393 F.3d at 1257. Applying Crish to instant
claim 1, we interpret the "said composition" limitation to require a mixture
of the active ingredient with a glycoside, but the earlier open transitional
phrase "containing" means that the claim can include additional components
along with the required active ingredient and glycoside. Therefore, we
interpret claim 1 as lacking any limitation excluding the presence of sugar or
other flavor additives. This is consistent with the depending claims, which
seek to add further components to the composition of claim 1.
We adopt the Examiner's findings of fact and reasoning regarding the
scope and content of the prior art (Final Act. 5-10; FF 2-14) and agree that
the claims are obvious over Machoczek, Samejima, and Felisaz.
Appellants contend that "Machoczek contains 23 examples, however,
not a single one of these examples refers to indomethacin and taste-masking
is never mentioned or even hinted at"; that "Samejima simply never
mentions anything about masking the bitter taste of a drug, let alone
specifically masking the bitter taste of indomethacin and/or acemetacin";
and that "F elisaz does not contain any teaching with reference to using a
chalcone glycoside and/or dihydrochalcone glycoside as a single species, let
alone that Felisaz could teach combining micronized indomethacin and/or
11
Appeal2015-004126
Application 11/997 ,348
acemetacin with a chalcone glycoside and/or dihydrochalcone glycoside
alone" (Br. 20, 22, 24).
We do not find these arguments persuasive. "Non-obviousness cannot
be established by attacking references individually where the rejection is
based upon the teachings of a combination of references." In re Merck &
Co., 800 F.2d 1091, 1097 (Fed. Cir. 1986). A reference "must be read, not
in isolation, but for what it fairly teaches in combination with the prior art as
a whole." Id.
Here, Machoczek and Samejima teach forming therapeutic tablets
using drugs including the anti-inflammatory indomethacin (FF 3, 7) that may
include flavorings (FF 4). And Samejima teaches that delivery of slightly
soluble drugs such as indomethacin is improved by micronization (FF 5, 7)
specifically teaching micrometer particles of indomethacin (FF 8). Felisaz
teaches combining masking agents with "therapeutic products having
unpleasant taste ... for example ... antiinflammatory ... agents" (FF 13)
while Samejima identifies indomethacin as an anti-inflammatory agent (FF
7).
We therefore agree with the Examiner's analysis that this combination
falls squarely within KSR's guidance that predictable combination of known
elements are likely obvious, and particularly that the use of a masking agent
with a known drug to improve the taste of that drug and "to hide the taste of
the pharmaceutical ingredient" would have been obvious (see Ans. 7). This
is consistent with the traditional adage that a spoonful of sugar helps the
medicine go down (see FF 9 "Traditionally, masking agents for unpleasant
pharmaceutical tastes are used whenever the patient, especially a young
12
Appeal2015-004126
Application 11/997 ,348
child, has to take the medicament orally .... For example, we can cite
sweeteners").
Appellants contend that "surprising and inventive feature of the
defined powdery form is that it needs only a small amount of the specific
taste-making compound to mask the taste which allows the production of
oral administration forms, such as pellets, containing a surprisingly high
amount of active ingredient" (Br. 1 7).
We find this argument unpersuasive because Felisaz suggests that
only 4.6 % masking agent was required to mask the taste of 95.5 % quinine,
a bitter pharmaceutical, suggesting that Felisaz would have expected low
amounts of the masking agent to effectively function (FF 14 ). See In re
Skoner, 517 F.2d 947, 950 (CCPA 1975) ("Expected beneficial results are
evidence of obviousness of a claimed invention. Just as unexpected
beneficial results are evidence ofunobviousness.") We note that the weight
ratio of the active agent quinine to masking agent in Example 14 is 500
mg/23.56 mg (FF 14) or 21:1, requiring lower amounts of masking agent
than any pending claim.
In addition, claim 1 includes no limitations regarding the relative
amounts of the taste-masking compound relative to the active compound, so
the claims are not commensurate in scope with this argued result. See In re
Tiffin, 448 F.2d 791, 792 (CCPA 1971) ("objective evidence ofnon-
obviousness must be commensurate in scope with the claims which the
evidence is offered to support").
Appellants contend that "[a]ccording to Samejima, a mixture of the
micronized active compound with a high amount of a sugar or a sugar
13
Appeal2015-004126
Application 11/997 ,348
alcohol is always obtained, which is undesirable for the present invention.
Without the addition of a sugar or a sugar-alcohol, the micronization as
claimed in Samejima is impossible to obtain" (Br. 21 ). Appellants
contend that in "the present invention, the active ingredient is used in a
micronized form, whereby the micronized form has been obtained by
conventional micronization without the addition of any additive, such as a
sugar or alcohol as is required by Samejima" (id.).
We find this argument unpersuasive because claim 1 does not exclude
the presence of sugar or sugar alcohols, nor does claim 1 require
micronization occur without the presence of sugar or sugar alcohols. See In
re Self, 671F.2d1344, 1348 (CCPA 1982) ("[A]ppellant's arguments fail
from the outset because ... they are not based on limitations appearing in
the claims.") Claim 1 simply requires that the "micronized form has been
obtained by micronization using mechanical means," an element taught by
Samejima, who teaches the use of mechanical mills (FF 6). Indeed, claim 1
expressly recites that the composition may contain, "optionally other
additives," positively permitting the presence of additional components such
as sugar or sugar alcohols, rather than excluding these components.
Appellants contend that "according to the present invention, a
chalcone glycoside and/or a dihydrochalcone glycoside alone is used in low
concentration. This is a surprising and unexpected occurrence which results
from a specific synergistic effect between the micronized indomethacin
and/ or acemetacin and the [] chalcone glycoside and/ or dihydrochalcone
glycoside alone" (Br. 24 ).
14
Appeal2015-004126
Application 11/997 ,348
We find this argument unpersuasive because claim 1 does not require
that the glycoside compounds are used alone, but simply requires the
presence of these compounds. As we discussed above, claim 1 lacks any
limitation excluding the presence of sugar or other flavor additives as taught
by the prior art of Samejima and Felisaz (FF 6, 10). "[L ]imitations are not to
be read into the claims from the specification." In re Van Geuns, 988 F.2d
1181, 1184 (Fed. Cir. 1993). Indeed, claim 1 expressly recites that the
composition may contain "optionally other additives," positively permitting
the presence of additional components rather than excluding these
components.
Appellants contend that:
One having skill in the art would have no motivation to
combine the teachings of Machoczek, Samejima or Felisaz in
order to create the present invention. This is due to the fact that
each of these references fail to even qualify as prior art
regarding the present invention. i\.dditionally, only hindsight
reconstruction based upon the instant specification would lead
the Examiner to the conclusion that the claims in the instant
application are rejected under § 103
(Br. 25-26).
We are not persuaded. While we are fully aware that hindsight bias
may plague determinations of obviousness, Graham v. John Deere Co., 383
U.S. 1, 36 (1966), we are also mindful that the Supreme Court has clearly
stated that the "combination of familiar elements according to known
methods is likely to be obvious when it does no more than yield predictable
results." KSR, 550 U.S. at 416. In the instant case, the ordinary artisan
applying Samejima's micronization to Machoczek's indomethacin tablets
15
Appeal2015-004126
Application 11/997 ,348
would have expected to "obtain better absorption as is taught by
[Samejima ]" (Ans. 27; cf FF 5 ("[T]o improve bioavailability of a drug
through micronization") ). The ordinary artisan would further have expected
that the Felisaz masking agent "can be used with a large number of
pharmaceutical or therapeutic products having unpleasant taste, belonging to
many different categories thereof, for example ... antiinflammatory ...
agents" (FF 13) in order to improve palatability of these agents, and would
therefore have had reason to include the masking agent in a composition
comprising the anti-inflammatory agent indomethacin (FF 7).
Conclusion of Law
The evidence of record supports the Examiner's conclusion that the
prior art renders claim 1 obvious.
D. 35 USC§ 103(a) over Nakamichi, Samejima, and Felisaz
The Examiner finds that Nakamichi teaches "[i]ndomethacin is taught
to be blended with a polymer resulting in a finely divided powder ... to be
used a powered or granules which can be used for oral administration" (Ans.
10). The Examiner relies upon Samejima and Felisaz as discussed above
(see Ans. 10-12).
The Examiner finds it would have been obvious to "use the
micronized form of indomethacin in order to increase the absorption of the
drug which would increase bioavailability" and "to use the task masking
system taught by [F elisaz] ... in order to product [sic] a more pleasant
tasting oral formulation which would result in better consumer acceptability"
(Ans. 12-13).
16
Appeal2015-004126
Application 11/997 ,348
The issue with respect to this rejection is: Does the evidence of
record support the Examiner's conclusion that the prior art renders claim 1
obvious?
Findings of Fact
15. Nakamichi teaches that "[s]olid dispersions are of use for an
enhanced solubility of drugs or for controlling the rate of release of a drug
from a dosage form or improving the bioavailability of drugs, thus being of
significant commercial value" (Nakamichi 1: 19-22).
16. Nakamichi teaches drugs including indomethacin (see
Nakamichi 3 :56) and exemplifies "[f]ive-hundred (500) grams of
indomethacin was blended with 2500 g ofhydroxypropylmethylcellulose
phthalate ... the composition was molded using a twin-screw extruder"
(Nakamichi 6:56---61 ).
Analysis
We adopt the Examiner's findings of fact and reasoning regarding the
scope and content of the prior art (Final Act. 10-13; FF 5-16) and agree that
the claims are obvious over Nakamichi, Samejima, and Felisaz.
Appellants contend that "Nakamichi fails to mention anything related
to the problem of masking the bitter taste of a drug, let alone of specifically
masking the bitter taste of indomethacin and/ or acemetacin in a micronized
state as defined in the present invention" (Br. 28).
We do not find this argument persuasive. As already noted, "[ n ]on-
obviousness cannot be established by attacking references individually
where the rejection is based upon the teachings of a combination of
references." In re Merck & Co., 800 F.2d at 1097. Here, it is the
17
Appeal2015-004126
Application 11/997 ,348
combination of references including Samejima and Felisaz that renders the
claims obvious, not Nakamichi's teaching of indomethacin in a bioavailable
tablet, alone (FF 15-16).
We recognize, but find unpersuasive, Appellants' reiterated arguments
regarding Samejima and Felisaz regarding the inclusion of additives such as
sugar or sugar alcohols (see Br. 29-32) for the reasons extensively discussed
already.
Conclusion of Law
The evidence of record supports the Examiner's conclusion that the
prior art renders claim 1 obvious.
E. 35 US.C. § 103(a) over Dell, Samejima, Zerbe, and Felisaz
The Examiner finds that Dell teaches pellet formulations "to obtain
sustained release without inhibiting bioavailability" (Ans. 13) and teaches
actives "selected from a short list which includes acemetacin ( 60 to 200 mg)
and indomethacin (10 to 60 mg)" (Ans. 14). The Examiner finds that Zerbe
teaches "citric acid and tartartaric acid are commonly used to enhance the
flavor of oral formulations" (Ans. 15). The Examiner relies upon Samejima
and Felisaz as discussed above (see Ans. 14--15).
The Examiner finds it obvious to "use micronized indomethacin as
taught by [Samejima] in the pellet taught by [Dell] because micronization
has long been recognized as a way to solve poor solubility in gastrointestinal
fluids of slightly soluble drugs" and "to include a sugar and enhancer
(flavonoid) in the formulation ... in order to mask the taste of the
pharmaceutical agent and prolong the sweetener flavor in the oral
formulation" (Ans. 15-16).
18
Appeal2015-004126
Application 11/997 ,348
The issue with respect to this rejection is: Does the evidence of
record support the Examiner's conclusion that the prior art renders claim 1
obvious?
Findings of Fact
17. Dell teaches "pellets of increased density which are lacquered
with a coating which is resistant to gastric juice are outstandingly suitable
for sustained release of substances of limited absorption (Dell I :40-44).
18. Dell teaches "[p ]referred active compounds for the pellet
formulations according to the invention are acemetacin ( 60 to 200 mg) ...
indomethacin (60 to 180 mg)" (Dell 2:38--40).
19. Zerbe teaches the "effect of flavors may be enhanced using
flavor enhancers like tartaric acid, citric acid vanillin, or the like" (Zerbe
3:35-37).
Analysis
We adopt the Examiner's findings of fact and reasoning regarding the
scope and content of the prior art (Final Act. 13-19; FF 5-14, 17-19) and
agree that the claims are obvious over Dell, Samejima, Zerbe, and Felisaz.
Appellants contend that:
Dell simply does not teach mechanically micronizing
indomethacin and/ or acemetacin. Dell also fails to teach
combining micronized indomethacin and/or acemetacin having
a defined average particle size, with a chalcone glycoside
and/or a dihydrochalcone glycoside. Dell does not contain any
teaching referring to taste-masking indomethacin and/or
acemetacin or to any other aspect of the present invention.
(Br. 35). Appellants also contend that "Zerbe does not contain any mention
or even hint at any reference to masking the bitter taste of the drugs
19
Appeal2015-004126
Application 11/997 ,348
indomethacin and/ or acemetacin and is therefore not relevant to the present
invention" (Br. 37).
We do not find these arguments persuasive. As already noted, "[n]on-
obviousness cannot be established by attacking references individually
where the rejection is based upon the teachings of a combination of
references." In re Merck & Co., 800 F.2d at 1097. Here, it is the
combination of references of Dell and Zerbe including Samejima and Felisaz
that renders the claims obvious, not Dell's teaching of acemetacin or
indomethacin in a bioavailable tablet (FF 17-18) and Zerbe's teaching of
flavor enhancers (FF 19), alone.
We recognize, but find unpersuasive, Appellants' reiterated arguments
regarding Samejima and Felisaz and the inclusion of additives such as sugar
or sugar alcohols (see Br. 36-39) for the reasons extensively discussed
above.
SUMMARY
In summary, we affirm the rejection of claims 1, 9, and 10 under
35 U.S.C. § 112, second paragraph, as indefinite.
We summarily affirm the rejection of claim 9 under 35 U.S.C. § 112,
fourth paragraph, as failing to further limit the subject matter of a previous
claim.
We affirm the rejection of claim 1 under 35 U.S.C. § 103(a) as
obvious over Machoczek, Samejima, and Felisaz. Claims 2, 4--11, 16, 17,
and 28-30 fall with claim 1.
20
Appeal2015-004126
Application 11/997 ,348
We affirm the rejection of claim 1 under 35 U.S.C. § 103(a) as
obvious over Nakamichi, Samejima, and Felisaz. Claims 24 and 25 fall with
claim 1.
We affirm the rejection of claim 1, under 35 U.S.C. § 103(a) as
obvious over Dell, Samejima, Zerbe, and Felisaz. Claims 2, 4--8, 19--22, 24,
25, and 31 fall with claim 1.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).
AFFIRMED
21