Ex Parte Woodward et al

Board of Patent Appeals and Interferences

Sep 12, 2008

10136240 (B.P.A.I. Sep. 12, 2008)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte DAVID F. WOODWARD and GYORGY AMBRUS
__________

Appeal 2008-4070
Application 10/136,240
Technology Center 1600
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Decided: September 12, 2008
__________

Before TONI R. SCHEINER, ERIC GRIMES, and FRANCISCO C.
PRATS, Administrative Patent Judges.

PRATS, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a liquid
composition containing a cationic therapeutic component in an ion-pair
complex with an efficacy enhancing component. The Examiner has rejected
the claims as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We
reverse.
STATEMENT OF THE CASE
Appeal 2008-4070
Application 10/136,240

Claims 1, 3, 7-11, 13, 16, 17, 19, 20, 22, 25-28, and 40 are pending
and on appeal (App. Br. 5). Claims 1, 11, 20, and 40 are the appealed
independent claims. Claim 20 is representative and reads as follows:
20. A liquid composition comprising:
an ophthalmically acceptable cationic therapeutic
component selected from the group consisting of NMDA
antagonists, antibacterials, antihistamines, decongestants,
antiinflammatories, antiparasitics, miotics, anticholinergics,
adrenergics, antivirals, local anesthetics, antifungals,
amoebicidals, trichomonocidals, analgesics, mydriatics,
antiglaucoma drugs, carbonic anhydrase inhibitors, ophthalmic
diagnostic agents, ophthalmic agents used as adjuvants in
surgery, chelating agents, antineoplastics, antihypertensives,
muscle relaxants, diagnostics, and mixtures thereof
provided in a therapeutically effective amount; and
an efficacy enhancing component having one, two,
or three negative charges provided in an amount greater than
0.2% (w/v) and less than about 10% (w/v) and being effective
to enhance the pharmacokinetic disposition of the therapeutic
component, to enhance the movement of the therapeutic
component across a lipid membrane, or a biological membrane
under physiological conditions, and to enhance the permeability
of the therapeutic component, from about 80% to about 100%
of the therapeutic component present in complex with the
efficacy enhancing component, the efficacy enhancing
component being present in an ion-pair complex with the
therapeutic component so that a ratio of electrical charge from
the efficacy enhancing component to electrical charge from the
therapeutic component is at least about 1:1 the complex
remaining substantially intact in an aqueous environment, and
each of the enhanced effects being relative to the effect
obtained with the therapeutic component without the efficacy
enhancing component.

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Claims 1, 3, 7-11, 13, 16, 17, 19, 20, 22, 25-28, and 40 stand rejected
under 35 U.S.C. 103(a) as being unpatentable over Maurer1 (Ans. 3-6).2
OBVIOUSNESS
ISSUE
The Examiner cites Maurer as disclosing “a quinoxaline containing
composition and the composition comprises [a] pharmaceutically acceptable
carrier such as hydroxypropylmethyl cellulose, sodium chloride (Example
6). Hydroxypropylmethyl cellulose is a non-ionic polymer and meets the
limitation of efficacy enhancer and solubilizer in claims 1, 11, 16, 20, 25 and
40” (Ans. 3). The Examiner points out that the “quinoxaline compounds are
formulated as compositions containing pharmaceutically acceptable carriers
(column 8, lines 46-60) and the carriers suitable for the quinoxaline
compositions” include stearic acid (id. at 3-4 (citing Maurer, col. 8, l. 62,
through col. 9, l. 9)).
Based on these teachings, the Examiner finds that “[t]he quinoxaline,
an N-methyl-D-aspartate (NMDA) antagonist meets the limitation of
NMDA antagonist recited in the amended claims 1, 11, 20 and 40 and claims
3,13, and 22” (id. at 4). The Examiner also finds that “[s]tearic acid, a fatty
acid, having one carboxylic acid group and hydroxypropylmethyl cellulose
meet the limitation of the efficacy-enhancing component” (id.). The

1 U.S. Patent No. 5,834,470, issued Nov. 10, 1998.
2 The Examiner’s Answer also contains a provisional obviousness-type
double patenting rejection over certain claims of Application Serial No.
09/847,935 (Ans. 6-7). Our review of that application, however, indicates
that the conflicting application was abandoned on July 11, 2008. The
provisional double patenting rejection is therefore moot, and will not be
discussed further.
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Examiner reasons that the claimed ion-pair complex “reads on a mixture
containing a therapeutic agent and efficacy enhancing component and
specifically, the instant specification does not teach how such a complex is
formed except that it appears to be formed by bringing the TC [(therapeutic
component)] and EEC [(efficacy enhancing component)] in a solution” (id.).
The Examiner concedes that, while Maurer’s composition contains an
efficacy enhancing component and a quinoxaline therapeutic component,
Maurer does not disclose the molar ratio of the two ingredients (id. at 5).
However, the Examiner contends, “since an ion-pair complex forms between
the therapeutic component (TC) and the efficacy enhancing component
(EEC) by combining the EEC and the TC, it flows that a certain amount of
TC combines with a certain amount of the EEC” (id.).
Thus, the Examiner contends, the disclosed ingredients when
combined would have yielded the claimed molar ratio of therapeutic
component to efficacy enhancing component because the “claims broadly
claim a large number of classes of therapeutic components, [including] the
class of NMDA antagonists [which] reads on the quinoxaline of Maurer.
Secondly, the efficacy enhancing component has one, two or three negative
charges and read[s on] hydroxypropylmethyl cellulose or stearic acid” (id.).
Specifically, the Examiner contends, “the stearic acid which has one
anionic charge would combine with one cationic drug in a 1:1 ratio; the
hydroxypropylmethyl cellulose having three negative charges would
combine with a cationic drug that has one cationic side/end” (id. at 5-6).
The Examiner concludes that “[i]t therefore flows that [the claimed] molar
ratio combination between the cationic drug and the EEC would be obvious”
(id. at 6).
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Appellants contend that the Examiner has not established a prima
facie case of obviousness because the hydroxypropylmethyl cellulose used
in Maurer’s compositions is not an anionic compound capable of
complexing with the quinoxaline in those compositions (see App. Br. 16),
and because the stearic acid used in Maurer’s compositions is only used in
solid compositions, not liquid compositions as recited in the claims on
appeal (see id. at 17).
The issue with respect to the obviousness rejection, therefore, is
whether the Examiner has made a prima facie case that one of ordinary skill
in the art would have considered claims 1, 3, 7-11, 13, 16, 17, 19, 20, 22, 25-
28, and 40 obvious in view of Maurer.
FINDINGS OF FACT
1. Maurer discloses “substituted 6-(2-imidazolinylamino)quinoxaline
compounds. The compounds have been found to be selective alpha-2
adrenoceptor agonists and are useful for treatment of one or more of
respiratory disorders, particularly nasal congestion; ocular disorders,
particularly glaucoma; and gastrointestinal disorders, particularly diarrhea”
(Maurer, col. 1, ll. 9-15).
2. With respect to suitable carriers for its therapeutic compounds,
Maurer discloses:
Some examples of substances which can serve as
pharmaceutically-acceptable carriers or components thereof are
sugars, such as lactose, glucose and sucrose; starches, such as
corn starch and potato starch; cellulose and its derivatives, such
as sodium carboxymethyl cellulose, ethyl cellulose, and methyl
cellulose; powdered tragacanth; malt; gelatin; talc; solid
lubricants, such as stearic acid and magnesium stearate;
calcium sulfate; vegetable oils, such as peanut oil, cottonseed
oil, sesame oil, olive oil, corn oil and oil of theobroma; polyols
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such as propylene glycol, glycerine, sorbitol, mannitol, and
polyethylene glycol; alginic acid; emulsifiers, such as the
Tweens®; wetting agents, such sodium lauryl sulfate; coloring
agents; flavoring agents; tableting agents, stabilizers;
antioxidants; preservatives; pyrogen-free water; isotonic saline;
and phosphate buffer solutions.

(Maurer, col. 8, l. 61, through col. 9, l. 9 (emphasis added).)
3. Maurer discloses that tablets containing its therapeutic compounds
“typically comprise conventional pharmaceutically-compatible adjuvants as
inert diluents, such as calcium carbonate, sodium carbonate, mannitol,
lactose and cellulose; binders such as starch, gelatin and sucrose;
disintegrants such as starch, alginic acid and croscarmelose; lubricants such
as magnesium stearate, stearic acid and talc” (Maurer, col. 9, ll. 29-34).
4. Example 3 of Maurer discloses a tablet that contains stearic acid
(Maurer, col. 12, ll. 24-39).
5. Appellants state, and the Examiner does not dispute, that “stearic acid
has a melting temperature of 69.6 °C (157.3 °F)” (App. Br. 19).
6. Maurer discloses that sublingual and buccal dosage forms of
compositions containing its therapeutic compounds “typically comprise one
or more of soluble filler substances such as sucrose, sorbitol and mannitol;
and binders such as acacia, microcrystalline cellulose, carboxymethyl
cellulose and hydroxypropyl methyl cellulose” (Maurer, col. 9, l. 65, through
col. 10, l. 2).
7. Example 6 of Maurer discloses an intranasal gel composition that
contains hydroxypropyl methylcellulose (Maurer, col. 13, ll. 1-16).
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8. In finding that Maurer disclosed compositions having the nonionic
solubilizer recited in claim 7, the Examiner found that
“[h]ydroxypropylmethyl cellulose is a non-ionic polymer” (Ans. 3).
9. In describing compounds useful as solubilizers, the Specification
states “[e]xamples of nonionic solubilizer components include, without
limitation, poly(oxyethylene)- poly(oxypropylene) block polymers,
polysorbate 80, polyvinyl alcohol, polyvinylpyrrolidine,
hydroxypropylmethyl cellulose and the like and mixtures thereof” (Spec. 23
(emphasis added)).
10. In describing compounds useful as efficacy enhancing agents, the
Specification states “[e]xamples of anionic polymers which may have
multiple anionic charges include: . . .
cellulose derivatives:
carboxymethylcelluloses
metal carboxymethylhydroxyethylcelluloses
hydroxypropylmethylcelluloses”
(Spec. 16-17.)
PRINCIPLES OF LAW
In proceedings before the Patent and Trademark Office,
the Examiner bears the burden of establishing a prima facie
case of obviousness based upon the prior art. “[The Examiner]
can satisfy this burden only by showing some objective
teaching in the prior art or that knowledge generally available to
one of ordinary skill in the art would lead that individual to
combine the relevant teachings of the references.”

In re Fritch, 972 F.2d 1260, 1265 (Fed. Cir. 1992) (citations omitted,
bracketed material in original). Furthermore, “[e]ven when obviousness is
based on a single prior art reference, there must be a showing of a suggestion
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or motivation to modify the teachings of that reference.” In re Kotzab, 217
F.3d 1365, 1370 (Fed. Cir. 2000).
Thus, as the Supreme Court recently pointed out:
[I]t can be important to identify a reason that would have
prompted a person of ordinary skill in the relevant field to
combine the elements in the way the claimed new invention
does . . . because inventions in most, if not all, instances rely
upon building blocks long since uncovered, and claimed
discoveries almost of necessity will be combinations of what, in
some sense, is already known.

KSR Int'l Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007).
When evaluating claims for obviousness, “the prior art as a whole
must be considered. The teachings are to be viewed as they would have
been viewed by one of ordinary skill.” In re Hedges, 783 F.2d 1038, 1041
(Fed. Cir. 1986). Moreover, “‘[i]t is impermissible within the framework of
section 103 to pick and choose from any one reference only so much of it as
will support a given position, to the exclusion of other parts necessary to the
full appreciation of what such reference fairly suggests to one of ordinary
skill in the art.’” Id. (quoting In re Wesslau, 353 F.2d 238, 241 (CCPA
1965)). The test of obviousness, therefore, is “whether the teachings of the
prior art, taken as a whole, would have made obvious the claimed
invention.” In re Gorman, 933 F.2d 982, 986 (Fed. Cir. 1991).
ANALYSIS
We agree with Appellants that the Examiner has not made a prima
facie case that one of ordinary skill in the art would have considered the
rejected claims obvious in view of Maurer.
Each of independent claims 1, 11, and 20, recites a liquid composition
that contains a cationic therapeutic component and an efficacy enhancing
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component that contains one, two, or three negative charges. Independent
claim 40 recites a liquid composition that contains a cationic therapeutic
component and an efficacy enhancing component that contains a fatty acid.
We agree with the Examiner that stearic acid is a fatty acid that has a
single negative charge, and that Maurer discloses stearic acid as a suitable
carrier for its therapeutic quinoxaline compounds (see FF 2, 3). However,
we do not agree with the Examiner that one of ordinary skill in the art would
have been prompted by Maurer to combine stearic acid with the disclosed
quinoxaline compounds when making a liquid composition, as recited in the
appealed claims.
Specifically, Maurer discloses stearic acid as a “solid lubricant[]”
(Maurer, col. 8, l. 67 (FF 2)) that is used as an adjuvant ingredient when
making tablets (FF 3, 4). Maurer does not include stearic acid in any liquid
formulations. Moreover, as Appellants point out, and the Examiner does not
dispute, stearic acid has a relatively high melting point of 69.6 °C (157.3 °F)
(see FF 5). We therefore agree with Appellants that Maurer does not
provide a teaching that would have suggested to one of ordinary skill that it
would be suitable or desirable to prepare a liquid formulation that contains
stearic acid in combination with a quinoxaline compound, as recited in the
appealed claims.
The Examiner argues that the claims do not exclude meltable
compounds, and that “substances such as stearic acid, though having a
melting point 160 °F as stated by appellant can be dissolved in suitable
solvents for use” (Ans. 9). The Examiner also argues that “Appellant’s
contention about the melting point of stearic acid would also apply to
appellant’s use of fatty acids in composition of claim 16. It is also noted that
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appellant’s specification at page 14, line 23 names stearic acid as a fatty
acid” (id. at 9-10).
We are not persuaded by these arguments. The Examiner does not
point to any teaching in Maurer suggesting that it would be suitable or
desirable to provide the disclosed compositions at a temperature that would
be sufficient to melt stearic acid. Moreover, while it may be true that
compounds such as stearic acid can be converted to a liquid form at lower
temperatures given the appropriate solvent, the Examiner has not explained
where or why Maurer would have suggested to one of ordinary skill that it
would be desirable to convert Maurer’s stearic acid carrier to a liquid form
using a solvent.
We therefore do not agree with the Examiner that one of ordinary skill
would have been prompted to include stearic acid in the liquid formulations
of Maurer. The Examiner points to no other teaching or suggestion in
Maurer of combining its quinoxaline compounds with a fatty acid in a liquid
composition, as required by claim 40. We therefore reverse the Examiner’s
rejection of claim 40 as obvious over Maurer.
With respect to independent claims 1, 11, and 20, the Examiner urges
that Maurer’s hydroxypropyl methylcellulose (HPMC) meets the limitation
requiring the composition to contain an efficacy enhancing ingredient that
has one, two, or three, negative charges (Ans. 7-8). Specifically, the
Examiner urges that HPMC must meet that limitation because it is listed in
the Specification at pages 16-17 (FF 10) as being an efficacy enhancing
component that has multiple anionic charges (id.).
We are not persuaded by this argument. We note that the
Specification lists “hydroxypropylmethylcelluloses” among “cellulose
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derivatives” that “may have multiple anionic charges” (Spec. 16-17 (FF 10)
(emphasis added)). However, claims 1, 11, and 20 each require the efficacy
enhancing component to have one, two, or three negative charges.
The Examiner has not explained how the Specification’s inclusion of
hydroxypropyl methylcelluloses in a group of derivatives that may have
multiple anionic charges demonstrates that one of ordinary skill would have
recognized that Maurer’s hydroxypropyl methylcellulose necessarily has
one, two, or three negative charges.
Rather, when considering the obviousness of the claimed
compositions, the Examiner explicitly states that “[h]ydroxypropylmethyl
cellulose is a non-ionic polymer” (Ans. 3 (FF 8)). Moreover, in describing
compounds useful as solubilizers, the Specification lists
hydroxypropylmethyl cellulose as being a “nonionic solubilizer” (Spec. 23
(FF 9)). In our view, the most reasonable reading of the Specification’s
characterizeation of HPMC as nonionic and “hydroxypropylmethyl-
celluloses” as cellulose derivatives that “may have multiple charges” is that
HPMC itself is nonionic but derivatives of hydroxypropylmethylcellulose
(i.e., “hydroxypropylmethylcelluloses”) can have multiple anionic charges.
The Examiner has not explained why one of ordinary skill viewing Maurer
would have considered it obvious to use a hydroxypropyl methylcellulose
derivative having one, two, or three negative charges in Maurer’s
compositions.
Given these facts, we find that a preponderance of the evidence does
not support the Examiner’s assertion that hydroxypropyl methylcellulose
meets the limitation in claims 1, 11, and 20 requiring an efficacy enhancing
component with one, two, or three negative charges. Moreover, as discussed
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above, we do not agree with the Examiner that one of ordinary skill viewing
Maurer would have considered it obvious to include stearic acid in the liquid
composition of claims 1, 11, and 20. We therefore reverse the Examiner’s
rejection of claims 1, 11, and 20, and their dependent claims 3, 7-10, 13, 16,
17, 19, 22, and 25-28, as being obvious over Maurer.
SUMMARY
We reverse the Examiner’s rejection of claims 1, 3, 7-11, 13, 16, 17,
19, 20, 22, 25-28, and 40 under 35 U.S.C. 103(a) as being unpatentable over
Maurer.
REVERSED

cdc

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