Ex Parte Chang et al

Patent Trial and Appeal Board

Mar 16, 2016

12589680 (P.T.A.B. Mar. 16, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
12/589,680 10/27/2009
29085 7590 03/16/2016
HOW ARD EISENBERG, ESQ.
1220 LIMBERLOST LANE
GLADWYNE, PA 19035
FIRST NAMED INVENTOR
YunikChang
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.
767.0191 5797
EXAMINER
MAIER, LEIGH C
ART UNIT PAPER NUMBER
1673
MAILDATE DELIVERY MODE
03/16/2016 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 YUNIK CHANG and GORDON J. DOW
Appeal2013-010423
Application 12/589,680
Technology Center 1600
Before DONALD E. ADAMS, DEMETRA J. MILLS, and
JEFFREY N. FREDMAN, Administrative Patent Judges.
FREDMAN, Administrative Patent Judge.
DECISION ON APPEAL
r-T"I .. • • .. 1 .. ,..... ,_ TT r'1 I'\ l\ -1,..... Al • "1 • "1 • , ims 1s an appear unaer j) u.~.L. s U4 mvo1vmg crnnns to a
pharmaceutical composition of metronidazole. The Examiner rejected the
claims as obvious and on the ground of obviousness-type double patenting.
We have jurisdiction under 35 U.S.C. § 6(b). We affirm.
1 Appellants identify the Real Party in Interest as Dow
Pharmaceutical Sciences, Inc. (see App. Br. 3).
Appeal2013-010423
Application 12/589,680
Statement of the Case
Background
"Compositions containing metronidazole for treatment of
dermatologic disorders are available in cream, lotion and gel forms ...
Aqueous-based gel compositions are limited to a concentration of
metronidazole of 0. 7 5% because of the poor solubility of metronidazole in
water" (Spec. 2, 11. 1-17).
The Claims
Claims 6, 7, and 9-1 7 are on appeal. 2 Independent claims 6 and 14
are representative and read as follows:
6. A pharmaceutical composition comprising water,
metronidazole, niacinamide or niacin, phenoxyethanol, a
gelling agent, and optionally a water miscible organic
solvent at a concentration of 10% w/w or less, wherein the
concentration of metronidazole dissolved in the composition
is higher than 0.75% w/w, and wherein the composition is
free of ethyl alcohol.
14. An aqueous solution for topical application to skin,
the aqueous solution comprising methylparaben,
propylparaben, phenoxyethanol, hydroxyethyl cellulose in
an amount such that the aqueous solution forms a gel, a
solubility enhancing system comprising 0.75% to 2% w/w
niacin or niacinamide, and 1 % w/w metronidazole dissolved
in the aqueous solution, wherein the aqueous solution is
physically stable when stored for one week at 5° C.
The Issues
A. The Examiner rejected claims 6, 7, and 9-17 under 35 U.S.C. § 103(a)
over Borgman,3 Chien,4 Coffman,5 and Modak6 (Ans. 2--4).
2 Claims 1-5 and 8 were cancelled (see Final Action 6/27/2011).
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Appeal2013-010423
Application 12/589,680
B. The Examiner rejected claim 6, 7, and 9-17 under the judicially
created doctrine of obviousness-type double patenting as being unpatentable
over claim 3 of US Patent No. 6,881,726,7 Borgman, and Modak (Ans. 4--5).
C. The Examiner rejected claim 6, 7, and 9-17 under the judicially
created doctrine of obviousness-type double patenting as being unpatentable
over claim 33 of U.S. Patent No. 7,348,317,8 Borgman, and Modak (Ans. 5).
Findings of Fact
1. Borgman teaches " [a] composition of the invention
advantageously comprises, in general, at least about 0.1 weight percent
metronidazole .... Preferably metronidazole is present in an amount in the
range of about 0.1 % to about 2%" (Borgman, col. 14, 11. 16-20).
3 Borgman, US 5,536,743, issued July 16, 1996.
4 Chien et al., US 4,032,645, issued June 28, 1977.
5 Coffman et al., Hydrotropic Solubilization-Mechanistic Studies,
13 PHARM. RES. (10), 1460-1463 (1996).
6 Modak et al., US 5,708,023, issued Jan. 13, 1998.
7 U.S. patent No. 6,881,726, issued Apr. 19, 2005.
8 U.S. patent No. 7,348,317, issued Mar. 25, 2008.
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Appeal2013-010423
Application I2/589,680
2. Example 7 of Borgman is reproduced below:
EXA.:."\iPLE 7
CQ~slci:ws l
{B-£1!:rt:D 1'1atm.md=1'l:. Gel C=i:iria!tirui~
P~ E..~~d:tmenQ
M.ettaaM.aml!!,
"~btlm
Pra;~ilenf Glyccl
M~l~n
Prnwl ?m:l:trn
NaOH 1!J% ~;!lb:!lc:i. (q.s.~
w~~.~}
~J-1
1-2
O..O:S
0-l:'i
IHlS
1Ml2
pH. 3 .. <'5-4.25
l.00
Example 7 teaches an aqueous buffered metronidazole gel
composition comprising, inter alia, metronidazole (O. I-I wt%), Carbopol
934P, propylene glycol, methyl paraben, propyl paraben and water, which is
free of ethyl alcohol (Borgman, col. 20, 11. 20-35).
3. The Specification teaches that Carbopol 934P is an example of
a suitable gelling agent (Spec. 8, 11. 22-23).
4. Borgman teaches that "[high] concentrations of tissue-drying
ingredients (e.g. alcohols and acetone), which are found, for example, in
some preparations to promote drug solubility, are also avoided. Such
ingredients at high concentration may excessively dry the patient's vaginal
wall causing undesirable discomfort" (Borgman, col. I 6, 11. 25-30).
5. Chien teaches that:
a practical way of administering a parenteral dose of
metronidazole was not available since the aqueous solubility
of metronidazole is only about I 00 mg.II 0 ml. and a
practical dosage is in the 500-650 mg.II 0 ml. range ... it
has now been found that the required concentration of 500-
650 mg.II 0 ml. of metronidazole can be attained ... Thus, a
solvent system suitable for an injectable solution containing
500-650 mg.II 0 ml. of metronidazole is comprised of: ...
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Appeal2013-010423
Application 12/589,680
10-30% v/v aqueous buffer ... 1-5% w/v hydrotropic agent
... 5-15% v/v polyhydroxyl alcohol ... Desirable
polyhydroxyl alcohols include ... propylene glycol. . . . A
particularly preferred hydrotropic agent is nicotinamide.
(Chien, col. 1, 11. 9-13; col. 2, 11. 16---53). We take notice that nicotinamide
is an alternate name for niacinamide. 9
6. Park teaches that:
Hydrotropy refers to a solubilization process whereby the
addition of large amounts of a second solute results in an
increase in the aqueous solubility of a poorly soluble
compound ... H ydrotropic agents (or hydrotropes) are
compounds that, at high concentrations, solubilize poorly
water-soluble molecules in water .... At concentrations
higher than the minimal hydrotrope concentration,
hydrotropic agents self-associate and form noncovalent
assemblies of lowered polarity, i.e., nonpolar microdomains,
which solubilize hydrophobic solutes.
(Park ii 33).
7. Coffman teaches that: "[ n ]icotinamide, vitamin B3, was chosen
as the model hydrotropic agent because of its ability to solubilize a wide
variety of compounds" (Coffman 1460, col. 2).
8. Modak teaches that: "[e]xamples of anti-microbial agents
include ... methyl paraben ... propyl paraben ... phenoxyethanol"
(Modak, col. 4, 11. 55---61 ).
9. Claims 1-3 of US patent No. 6,881,726 read as follows:
1. An aqueous solution that is physically stable for at
least one week at 5° C. comprising metronidazole, a first
solubility enhancing agent which is betacyclodextrin, and a
9 See http://www. fda. gov IF ood/IngredientsPackagingLabeling/
GRAS/SCOGS/ucm260908.htm (accessed Mar. 2, 2016).
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Appeal2013-010423
Application 12/589,680
second solubility enhancing agent which is niacin or
niacinamide, wherein in the solution, the concentration of
metronidazole is about 1.0% w/w or higher, the
concentration ofbetacyclodextrin is 0.5% w/w or higher,
and the concentration of niacinamide or niacin is about 0.5%
w/w or higher.
2. The aqueous solution of claim 1 wherein the solubility
enhancing agent is niacinamide.
3. The aqueous solution of claim 2 which is a gel.
10. Claims 25 and 33 of US patent No. 7,348,317 read as follows:
25. An aqueous solution that is physically stable for at
least one week at 5° C. comprising metronidazole, a first
solubility enhancing agent which is betacyclodextrin, and a
second solubility enhancing agent which is niacin or
niacinamide, wherein in the solution, the concentration of
metronidazole is 0.75% w/w or higher and the first and
second solubility enhancing agents are present in amounts
that provide a synergistic effect on the solubility of
metronidazole.
33. The aqueous solution of claim 25 which is a gel.
A. 3 5 U.S. C. § 103 (a) over Borgman, Chien, Coffman and Modak
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!nt'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.
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Application 12/589,680
Analysis
We adopt the Examiner's findings of fact and reasoning regarding the
scope and content of the prior art (Ans. 2-5; FF 1-8) and agree that the
claims are rendered obvious by Borgman, Chien, Coffman and Modak. We
address Appellants' arguments below.
Appellants admit that "Borgman does disclose that the compositions
may comprise metronidazole at a concentration of from 0.1 % to 2%", but
contend that "Borgman is not an enabling reference for an aqueous
composition containing a dissolved concentration of metronidazole greater
than 0.75%" (App. Br. 13), and that "[i]n Example 1 ... Borgman does not
disclose whether the metronidazole in the composition was fully solubilized
or in solution" (App. Br. 14). Appellants further admit that "[a]dditional
compositions containing metronidazole at a concentration between 0.5% and
1 % are disclosed in Examples 2 to 8", but contend that "each of Examples 2
to 8 are prophetic examples", arguing that Example 1 utilizes the past tense,
whereas Examples 2 to 8 utilize the present tense (App. Br. 15).
We are not persuaded. "[A] prior art printed publication cited by an
examiner is presumptively enabling barring any showing to the contrary by a
patent applicant." In re Antor Media Corp., 689 F.3d 1282, 1288 (Fed. Cir.
2012). Where the prior art explicitly teaches a concentration of
metronidazole higher than 0.75% w/w in a water composition with a gelling
agent, and in the presence of solvents (water and propylene glycol), (FF 1--4)
Appellants have failed to establish a persuasive argument or evidentiary
basis to support a conclusion that "Borgman is not an enabling reference for
an aqueous composition containing a dissolved concentration of
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Application 12/589,680
metronidazole greater than 0.75%", or that the examples, prophetic or
otherwise, do not teach such a concentration (App. Br. 13-14; Reply Br. 4).
We recognize, but find unpersuasive, Appellants' argument that "all
of the examples of Borgman in which aqueous solutions of metronidazole
greater than 0.75% are disclosed would be understood by one of skill in the
art to pertain to a water-soluble analog of metronidazole" (App. Br. 16).
While Borgman defines "metronidazole" to include not only the base
compound, but also analogs and derivatives thereof (Borgman, col. 8, lines
27-33), Appellants neither identify specific support in Borgman's examples
that suggests the metronidazole ingredient necessarily encompasses an
"analog or derivative" nor do Appellants identify specific language in their
own Specification that excludes the salt or other derivative forms of
metronidazole from the scope of the instant claims. The mere statement
providing the chemical structure after the compound name at Spec. 1, 1. 11 is
insufficient to serve as a definition that excludes the salt form of the
compound. See In re Zletz, 893 F.2d 319, 322 (Fed. Cir. 1989) ("[D]uring
patent prosecution when claims can be amended, ambiguities should be
recognized, scope and breadth of language explored, and clarification
imposed.")
Appellants contend that:
[I]n Example 7 ... the composition may contain
metronidazole in aqueous solution or in aqueous suspension.
One of skill in the art, understanding that the aqueous
solubility of metronidazole is less than 1.0% would
understand that, at the lower end of the concentration range
of metronidazole, the metronidazole is in solution. However,
at the higher end of this range, the metronidazole would be
in suspension unless metronidazole were present as a salt or
an ester.
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Application 12/589,680
(App. Br. 16-17; cf Reply Br. 5---6).
We are not persuaded. The explicit language of Borgman is in the
alternative- "Aqueous Solutions or Suspensions", and of metronidazole
concentration of up to 1 % w/w (FF 2; emphasis added). Also, Appellants'
claims are directed to a pharmaceutical composition, and do not recite either
a solution or suspension per se. The arguments of counsel cannot take the
place of evidence in the record. In re Geisler, 116 F.3d 1465 (Fed. Cir.
1997) ("An assertion of what seems to follow from common experience is
just attorney argument and not the kind of factual evidence that is required to
rebut a primafacie case of obviousness.").
Appellants contend that "Chien does not disclose that niacinamide, by
itself and without the presence ofN,N-dimethylacetamide and alcohol, is
capable of increasing the concentration of metronidazole above its otherwise
saturated concentration" (App. Br. 18). Appellants also contend that "the
disclosure in Chien that niacinamide has a function as a hydrotropic agent
that works in an alcoholic/aqueous fluid with respect to the solubility of
metronidazole has no bearing on the function of niacinamide to increase the
solubility of metronidazole in an aqueous, alcohol-free, fluid" (App. Br. 20).
We are not persuaded. Even if Chien teaches a high concentration of
ethyl alcohol, Borgman teaches none in the examples, and even emphasizes
the need to avoid such in order to prevent excessively drying the patient's
vaginal wall and causing undesirable discomfort (FF 4). Moreover, Chien,
Coffman, and Park expressly teach the desirability of solubilizers, including
the combination of solubilizers such as nicotinamide with metronidazole (FF
5-7). "[O]ne cannot show non-obviousness by attacking references
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Application 12/589,680
individually where, as here, the rejections are based on combinations of
references." In re Keller, 642 F.2d 413, 426 (CCPA 1981). Further,
Appellants' use of the open transitional term "comprising" does not exclude
the presence ofN,N-dimethylacetamide or other organic solvents, with claim
6 solely excluding the presence of ethyl alcohol, and does not even exclude
other alcohols. Genentech, Inc. v. Chiron Corp., 112 F.3d 495, 501 (Fed.
Cir. 1997).
We recognize, but find unpersuasive, Appellants' separate arguments
regarding Park (see App. Br. 19) and Coffman, contending that while
"Coffman states that niacinamide is capable of solubilizing a wide variety of
compounds, Coffman does not mention or suggest metronidazole" (App. Br.
20). However, Appellants do not persuasively rebut the Examiner's reliance
on Coffman's express teaching to use niacinamide as a solubilizing agent
(FF 7), Park's teaching connecting hydrotropic and solubilizing agents (FF
6) in combination with Chien's teaching that niacinamide is a desirable
hydrotropic (i.e. solubilizing) agent for metronidazole itself (FF 5). See In
re Keller, 642 F.2d at 413.
We further recognize, but are not persuaded by Appellants arguments
regarding Modak that "if one of the listed anti-microbial agents is preferred,
it is evident that the agents in the list are not necessarily equivalents and,
therefore, the conclusion of the Examiner regarding the equivalence of
phenoxyethanol and methylparaben and propylparaben is clearly erroneous"
and that "prior art does not disclose or suggest that phenoxyethanol is an
equivalent to parabens" (App. Br. 21-22). Modak's teaching of the three
compounds as options in a list of exemplary anti-microbial agents
reasonably supports the Examiner's position that these compounds are
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Application 12/589,680
known equivalents that may be combined or substituted with one another.
This result is consistent with the Wrigley, where the Federal Circuit found a
"strong case of obviousness based on the prior art references of record. [The
claim] recites a combination of elements that were all known in the prior art,
and all that was required to obtain that combination was to substitute one
well-known ... agent for another." Wm. Wrigley Jr. Co. v. Cadbury Adams
USA LLC, 683 F.3d 1356, 1364 (Fed. Cir. 2012).
Conclusion of Law
The evidence of record supports the Examiner's conclusion that
Borgman, Chien, Coffman and Modak render claims 6 and 14 obvious under
35 U.S.C. § 103(a).
Band C. Obviousness-Type Double Patenting
Appellants contend as to both US patent 6,881,726 and US patent No.
7 ,348,317 that the claims of these patents: "call for betacyclodextrin as a
necessary feature, whereas the claims of the present application do not call
for betacyclodextrin" (App. Br. 23-24; Reply Br. 7-8).
We do not find this argument persuasive. We agree with the
Examiner that "[ n ]either, however, do the claims preclude beta cyclodextrin"
(Ans. 9; FF 9-10). That is, because claims 6 and 14 use the open
transitional phrase "comprising," these claims do not exclude the use of any
additional components such as betacyclodextrin. See Georgia-Pacific Corp.
v. U.S. Gypsum Co., 195 F.3d 1322, 1327 (Fed. Cir. 1999) (The transitional
term "comprising" is "inclusive or open-ended and does not exclude
additional, unrecited elements or method steps.")
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SUMMARY
We affirm the rejection of claims 6 and 14 under 35 U.S.C. § 103(a)
as obvious over Borgman, Chien, Coffman and Modak. Claims 7, 9-13, and
15-17 fall with claim 12. 37 C.F.R. § 41.37(c)(l)(iv).
We affirm the rejection of claim 6 on the ground of nonstatutory
obviousness-type double patenting as being unpatentable over claim 3 of
U.S. Patent No. 6,881,726, Borgman and Modak. Claims 7 and 9-17 fall
with claim 6. 37 C.F.R. § 41.37(c)(l)(iv).
We affirm the rejection of claim 6 on the ground of nonstatutory
obviousness-type double patenting as being unpatentable over claim 33 of
U.S. Patent No. 7,348,317, Borgman and Modak. Claims 7 and 9-17 fall
with claim 6. 37 C.F.R. § 41.37(c)(l)(iv).
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
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