Ex Parte Liang

Patent Trial and Appeal Board

Jun 14, 2013

10995942 (P.T.A.B. Jun. 14, 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.
10/995,942 11/24/2004 Likan Liang 063089-1600 5549
90368 7590 06/14/2013
Foley & Lardner LLP
3000 K STREET NW
SUITE 500
WASHINGTON DC, DC 20007-5109
EXAMINER
KISHORE, GOLLAMUDI S
ART UNIT PAPER NUMBER
1612
MAIL DATE DELIVERY MODE
06/14/2013 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
____________

Ex parte LIKAN LIANG
____________

Appeal 2011-010367
Application 10/995,942
Technology Center 1600
____________

Before FRANCISCO C. PRATS, ULRIKE W. JENKS, and JOHN G. NEW,
Administrative Patent Judges.

JENKS, Administrative Patent Judge

DECISION ON APPEAL
This is an appeal
1
under 35 U.S.C. § 134 involving claims directed to
reverse micelles. The Patent Examiner has rejected the claims as obvious.
We have jurisdiction under 35 U.S.C. § 6(b). We affirm.

1
Appellant states that the Real Party in Interest is Supernus
Pharmaceuticals, Inc. (App. Br. 3).
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Application 10/995,942

2
STATEMENT OF THE CASE
The Specification is directed to compositions that are in “the form of
reverse micelles, which are comprised of one or more non-ioinic [sic]
surfactants or a mixture of non-ionic and ionic surfactants, a hydrophilic
phase composed of one or more hydrophilic solvents and/or solubilizers
and/or aqueous media, and one or more therapeutically active, hydrophobic
agents.” (Spec. 3.)
Claims 1, 4-8, 15, 16, 19, 20, 23-25, and 27-34 are on appeal,
2
and can
be found in the Claims Appendix of the Appeal Brief (App. Br. 11-14).
Claim 1 is representative of the claims on appeal, and reads as follows:
1. A composition comprising a reverse micelle system, the
system comprising:
(a) a hydrophilic phase;
(b) a hydrophobic continuous phase; and
(c) at least one biologically active hydrophobic
therapeutic agent selected from the group consisting of
carbamazepine, oxcarbazepine, cyclosporine, eprosartan,
griseofulvin, angiotensin converting enzyme (ACE) inhibitors
or neutral endopeptidase (NEP) inhibitors, fibric acid,
fexofenadine, flutamide, glipizide, glyburide, isradipine,
loratadine, lovastatin, melphalan, nifedipine, proton pump
inhibitors, mitogen-activated protein (MAP) kinase inhibitors,
pralnacasan, pseudoephedrine, indomethacin, topiramate,
naproxen, phenytoin, sumatriptan, ergotamines, cannabinoids,
and pharmaceutically acceptable derivatives thereof,
wherein said composition comprises less than 10% of
triglycerides,
wherein all of the therapeutic agent is dissolved in the
hydrophobic continuous phase, and
wherein both phases comprise surfactants, solubilizers or
combinations thereof.

2
Claims 9-11 are withdrawn.
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3
The Examiner has rejected the claims as follows:
I. claims 1, 4-8, 15, 16, 19, 20, 23-25, and 27-33 under 35 U.S.C.
§ 112, second paragraph;
II. claims 1, 4-8, 15, 16, 19, 20, 23-25, and 27-33 under 35 U.S.C.
§ 103(a) as being unpatentable over Carlsson
3
in view of
Constantinides;
4

III. claims 1, 4-8, 15, 16, 19, 20, 23-25, and 27-33 under 35 U.S.C.
§ 103(a) as being unpatentable over Evans
5
alone or in
combination with Stergiopoulos;
6
and
IV. claims 1, 4-8, 15, 16, 19, 20, 23-25, and 27-33 under 35 U.S.C.
§ 103(a) as being unpatentable over Constantinides in view of
Stergiopoulos.
As Appellant does not argue the claims separately, we focus our
analysis on claim 1, and claims 4-11, 15, 16, 19, 20, 23-25, and 27-33 stand
or fall with that claim. 37 C.F.R. § 41.37 (c)(1)(vii).

I. Indefiniteness under 35 U.S.C. §112, second paragraph
The Examiner finds that claim 1 is unclear because it recites
“„wherein said composition comprises less than 10 % of triglycerides,
wherein all of the therapeutic agent is dissolved in the hydrophobic
continuous phase.” The Examiner finds that this is confusing; triglycerides

3
Anders Carlsson et al., US 5,716,639, issued Feb. 10, 1998.
4
Panos P. Constantinides et al., WO 03/047493 A2, published June 12,
2003.
5
Richard M. Evans et al., US 5,292,499, issued Mar. 8, 1994.
6
Nicholas Stergiopoulos et al., US 2003/0055028 Al, published Mar. 20,
2003.
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are hydrophobic and it is unclear whether the hydrophobic continuous phase
contains the triglycerides or the reverse micelles. (Ans. 5.)
The Examiner also finds that “[i]t is unclear . . . as to what the
reverse micelles are made of and if the active agent is present only in the
continuous phase, then what is the purpose of the reverse micelles?” (Id.)

Principle of Law
“The test for definiteness is whether one skilled in the art would
understand the bounds of the claim when read in light of the specification.”
Miles Laboratories, Inc. v. Shandon Inc., 997 F.2d 870, 875 (Fed. Cir.
1993).

Analysis
Appellant contends “that a plain reading of the claims leaves no doubt
that the claimed compositions as a whole comprise less than 10%
triglycerides.” (App. Br. 5.)
We find that Appellant has the better position. Here, the claim begins
with “a composition” and then continues with “wherein said composition
comprises less than 10% of triglycerides.” We agree with Appellant that the
claim makes it clear that “said composition . . .” is referring to a composition
comprising a reverse micelle system. Here the reverse micelle system
contains a hydrophilic phase and hydrophobic continuous phase, thus, the
triglycerides of the system being hydrophobic molecules would partition into
the hydrophobic phase.
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Appellant asserts that “the „purpose‟ of the claimed reverse micelles
or its components is irrelevant to the issue of definiteness as is their intended
use (i.e., „what does [the solubilizer] solubilize?).” (Reply Br. 5.)
We agree with the Appellant‟s position. In a reverse micelle the
hydrophobic phase is found on the outside of the micelle, and the
hydrophilic phase is on the interior. Just because in most reverse micelle
systems the active ingredient is packaged into the interior of the micelle does
not make it unclear that Appellant desires to do just the opposite.
We reverse the rejection of claims 1, 4-8, 15, 16, 19, 20, 23-25, and
27-33 under 35 U.S.C. § 112, second paragraph.

II. The Issue: Obviousness over Carlsson and Constantinides
The Examiner takes the position that Carlsson disclosed reverse
micelles containing cyclosporin in a continuous phase (Ans. 5) and that the
combination with Constantinides teaches lowering the triglyceride levels to
under 10% (id. at 6). “[T]he examiner points out . . . since a hydrophobic
agent will dissolve in a hydrophobic phase and not in an aqueous phase, it is
a scientific fact that if the continuous phase is a hydrophobic phase, it will
sequester within this hydrophobic phase.” (Id. at 9.)

Findings of Fact
The following finding of fact (“FF”) are supported by a
preponderance of the evidence of record.
1. Constantinides disclosed the production of “reverse micelle
compositions comprising a surfactant (e.g., a P-glycoprotein inhibitor), a
hydrophilic phase, and one or more biologically active molecules.”
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(Constantinides 6; Ans. 5.) “[T]he reverse micelle compositions comprise
less than 15%, less than 10%, less than 5%, or less than 2% by weight of
triglycerides.” (Constantinides 7; Ans. 5-6.)
2. Constantinides disclosed therapeutic agents such as: acyclovir,
azithromycin, clarithromycin, and dirithromycin. (Constantinides 24-27;
Ans. 5.)
3. Carlsson disclosed that “[l]ipophilic carriers may be organised
[sic] solutions, such as microemulsions or reverse micellar solutions, reverse
vesicles or water-in-oil emulsions.” (Carlsson, col. 1, ll. 36-38; Ans. 5.)
4. Carlsson disclosed that the “bioactive substance can be a
lipophilic drug such as . . . cyclosporin.” (Carlsson, col. 4, ll. 51-65; Ans.
5.)
5. The Specification provides that therapeutic hydrophobic agents
include: albuterol, acyclovir, carbamazepine, clarithromycin, cyclosposrin,
and dirithromycin, to name a few. (Spec. 33, original claims.)

Principle of Law
“In United States v. Adams, . . . [t]he Court recognized that when a
patent claims a structure already known in the prior art that is altered by the
mere substitution of one element for another known in the field, the
combination must do more than yield a predictable result.” KSR Int’l Co. v.
Teleflex Inc., 550 U.S. 398, 416 (2007).

Analysis
Appellant asserts that “[t]he Examiner has provided no rationale or
reason in support of the allegedly „obvious‟ modification.” (App. Br. 5.)
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We are not persuaded. Applying the KSR standard of obviousness to
the findings of fact, we agree with the Examiner that the ordinary artisan
would have reasonably selected cyclosporin as a hydrophobic drug as taught
by Carlsson (FF 4) with the reverse micelle composition as disclosed by
Constantinides (FF 1). Carlsson disclosed the production of reverse micelles
including cyclosporin, a known hydrophobic drug (FF 4). Constantinides
disclosed the production of reverse micelles including therapeutic
compounds such as acyclovir, azithromycin, clarithromycin, and
dirithromycin (FF 2), compounds that are known to be hydrophobic. The
Specification provides that these compounds are known hydrophobic drugs
(FF 6). The mere substitution of one hydrophobic molecule for another
hydrophobic molecule would have been obvious as long as it provided a
predictable result as it does under the present facts. KSR, 550 U.S. at 416.
Appellant asserts that the Carlsson and Constantinides cannot be
combined as a matter of law “because „a proposed modification cannot
render the prior art unsatisfactory for its intended purpose.” (App. Br. 6.)
We are not persuaded. A prior art reference is said to teach away
from an Applicant‟s invention “when a person of ordinary skill, upon
reading the reference, would be discouraged from following the path set out
in the reference, or would be led in a direction divergent from the path that
was taken by the applicant.” In re Gurley, 27 F.3d 551, 553 (Fed. Cir.
1994). “The prior art‟s mere disclosure of more than one alternative does
not constitute a teaching away from any of these alternatives because such
disclosure does not criticize, discredit, or otherwise discourage the solution
claimed.” In re Fulton, 391 F.3d 1195, 1201 (Fed. Cir. 2004). The
Examiner‟s position is that hydrophobic drug will sequester in a
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“hydrophobic phase and not in an aqueous phase, it is a scientific fact that if
the continuous phase is a hydrophobic phase, it will sequester [the drug]
within this hydrophobic phase.” (Ans. 9.) We find nothing in the
references, and Appellant has not directed us to any teaching in the
references, that would discourage the artisan from exchanging one
hydrophobic therapeutic compound for another, or suggesting that including
cyclosporine in Constantinides‟ composition would not result in a useful
therapeutic.
The Examiner finds that “both references are directed to same reverse
micellar compositions containing lipophilic active agents. One of ordinary
skill in the art reading both references would come to the conclusion that
triglyceride levels are not critical (one teaching high levels and the other
lower levels).” (Ans. 9.) Appellant has not provided evidence or any
persuasive technical reasoning to show that known hydrophobic drugs
behave differently in the system of Constantinides than in their system. We
agree with the Examiner and find nothing in the teachings of Carlsson and
Constantinides that would dissuade the ordinary artisan from making the
combination to arrive at reverse micelles containing a hydrophobic
therapeutic agent and having less than 10% triglyceride content.
Appellant asserts that the combination “fail[s] to teach reverse micelle
systems compositions „wherein all of the therapeutic agent is dissolved in
the hydrophobic continuous phase‟. The Examiner does not dispute this fact,
but intimates that „if the drug is hydrophobic, one would expect [the drug] to
be in the continuous‟ hydrophobic phase just as in the invention.‟” (App.
Br. 7.)
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We find that the Examiner has the better position. The Examiner has
provided sound reasoning for making the combination and arriving at the
conclusion that the hydrophobic drug will move into the hydrophobic phase.
Specifically, the Examiner finds that “a hydrophobic agent will dissolve in a
hydrophobic phase and not in an aqueous phase, it is a scientific fact that if
the continuous phase is a hydrophobic phase, it will sequester within this
hydrophobic phase.” (Ans. 9.) We recognize, but are not persuaded by,
Appellant‟s contention that Carlsson and Constantinides “fail to teach
reverse micelle systems compositions „wherein all of the therapeutic agent is
dissolved in the hydrophobic continuous phase.‟” (App. Br. 7.) Appellant
fails to identify any evidentiary basis on this record that rebuts the
Examiner‟s reasoning that like dissolves like. In re Geisler, 116 F.3d 1465,
1471 (Fed. Cir. 1997) (Argument of counsel cannot take the place of
evidence).
We conclude that the preponderance of the evidence of record
supports the Examiner‟s conclusion that the combination of Carlsson and
Constantinides renders obvious reverse micelle system of claim 1. We thus
affirm the rejection of claim 1 under 35 U.S.C. § 103(a) as being obvious; as
claims 4-8, 15, 16, 19, 20, 23-25, and 27-33 were not argued separately, they
fall with claim 1, and we affirm the rejection as to those claims as well. 37
C.F.R. § 41.37 (c)(1)(vii).

III. The Issue: Obviousness over Evans and Stergiopoulos
The Examiner takes the position that the composition is obvious over
the disclosure of Evans and Stergiopoulos because “[o]ne of ordinary skill in
the art would be motivated to use drugs such as cyclosporin in Evans with a
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reasonable expectation of success since Stergiopoulos teaches that steroids
and cyclosporin could be formulated in reverse micelle compositions.”
(Ans. 6-7.)

Findings of Fact
6. Evans disclosed pharmaceutical compositions such as steroids,
corticosteroids and prostaglandins can be incorporated into reverse micelle
vesicles. (Evans, 7, ll. 11-54; Ans. 6.)
7. Stergiopoulos disclosed that
Hydrophobic therapeutic agents, while poorly soluble in
aqueous solution, may be sufficiently lipophilic such that
therapeutically effective concentrations can be prepared in
triglyceride-based solvents forming colloidal oil particles, with
broad particle size distribution and relatively large sizes,
ranging from several hundred nanometers to several microns in
diameter. Reverse micelles containing oil(s), surfactant(s) and
an aqueous phase are also characterized as water-in-oil
microemulsions.
(Stergiopoulos, 4, ¶ 0028; Ans. 7.)
8. Stergiopoulos disclosed that “[t]he reverse micellar phase is
also known as L2. In the L2 phase, water forms the internal phase and the
hydrophobic tails of the lipid form the continuous phase.” (Stergiopoulos, 4,
¶ 0025; Ans. 7.)
9. Stergiopoulos disclosed using “cyclosporin.” (Stergiopoulos, 7,
claim 19; Ans. 7.)

Analysis
Appellant asserts that “Evans' undisputed description of an active
compound contained in reverse micelles and the present invention's active
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compound contained outside reverse micelles can be reconciled if Evans is
interpreted to teach hydrophilic drugs (as argued), and the claimed invention
is properly understood to encompass hydrophobic drugs.” (App. Br. 9.)
The Examiner contends that:
Although Evans uses the term, 'hydrophilic drug', certainly he
teaches both hydrophilic and hydrophobic drugs. If Evan's
intent is to convey that the hydrophobic drugs are derivatized so
that they would be hydrophilic, certainly he would not have
recite[d] some steroids in salts forms and some as free bases
which are hydrophobic.
(Ans. 10.) “Evans clearly teaches the use of Albuterol base and not a salt of
Albuterol. In addition, in claim 7, Evans clearly claims „mixing said
surfactant with salbutamol in its base or salt form‟ Albuterol (salbutamol)
is known in the art as a hydrophobic compound.” (Id.) The Examiner
contends that “[a] hydrophobic drug in a reverse micellar system in a
hydrophobic phase will not behave in a certain way in one composition and
behave in a different way in applicant's compositions.” (Ans. 11.)
We find that the Examiner has the better position. While the
Examiner recognized that Evans does not disclose any of the specific drugs
listed in the claims, the Examiner‟s position is that Evans did include the use
of hydrophobic drugs. The Examiner finds that:
Evans states, "the present invention include the following:
steroids such as beclametasone dipropionate, acetate, valerate
and free alcohols there of, atropine base, prednisolone,
formoterol base, hydrochlorine, fumarate and hemisulphate".
Furthermore, on col. 11, lines 64-66, Evans clearly teaches the
use of Albuterol base and not a salt of Albuterol. In addition, in
claim 7, Evans clearly claims "mixing said surfactant with
salbutamol in its base or salt form" Albuterol (salbutamol) is
known in the art as a hydrophobic compound.
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(Ans. 10.) We agree with the Examiner‟s finding that Evans teaches both
hydrophobic compounds as well as their hydrophilic salt derivatives. We
agree with the Examiner‟s position that the ordinary artisan would expect
that “a hydrophobic drug to behave the same way whether it is in applicant's
invention or in Evans, that is, to partition into the hydrophobic phase.” (Id.
at 11.) We agree with the Examiner‟s conclusion that substituting the
hydrophobic cyclosporin in the reverse micelles of Evans would lead to the
claimed composition. The mere substitution of one hydrophobic molecule
for another hydrophobic molecule is obvious. KSR, 550 U.S. at 416.
We conclude that the preponderance of the evidence of record
supports the Examiner‟s conclusion that the combination of Evans and
Stergiopoulos renders obvious reverse micelle system of claim 1. We thus
affirm the rejection of claim 1 under 35 U.S.C. § 103(a) as being obvious; as
claims 4-8, 15, 16, 19, 20, 23-25, and 27-33 were not argued separately, they
fall with claim 1, and we affirm the rejection as to those claims as well. 37
C.F.R. § 41.37 (c)(1)(vii).

IV. The Issue: Obviousness over Constantinides and Stergiopoulos
The Examiner takes the position that “[Constantinides] discloses
reverse micelle compositions containing the same surfactants, solubilizers
and active agents such as acyclovir, vitamins and anti-cancer agents such as
Adriamycin, Irinotecan (which is hydrophobic).” (Ans. 7.) The Examiner
concludes that “[o]ne of ordinary skill in the art would be motivated to use
drugs such as cyclosporin in [Constantinides] with a reasonable expectation
of success since Stergiopoulos teaches that steroids and cyclosporin could be
encapsulated in reverse micelles.” (Id.)
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Analysis
Appellant asserts that in “the reverse micelle system of
[Constantinides], by contrast, „[t]he biologically active molecule is
contained within the hydrophilic phase,‟ Stergiopoulos, even if presumed to
be combined properly with [Constantinides], provides no relief.” (App. Br.
9.)
We are not persuaded. Under KSR the mere substitution of one
hydrophobic molecule for another hydrophobic molecule is obvious. KSR,
550 U.S. at 416. Appellant has not provided evidence or any persuasive
technical reasoning to show that known hydrophobic drugs would not
sequester into the hydrophobic phase in the reverse micelles of
Constantinides or Stergiopoulos.
We conclude that the preponderance of the evidence of record
supports the Examiner‟s conclusion that the combination of Constantinides
and Stergiopoulos renders obvious reverse micelle system of claim 1. We
thus affirm the rejection of claim 1 under 35 U.S.C. § 103(a) as being
obvious; as claims 4-8, 15, 16, 19, 20, 23-25, and 27-33 were not argued
separately, they fall with claim 1, and we affirm the rejection as to those
claims as well. 37 C.F.R. § 41.37 (c)(1)(vii).

V. Non Statutory Obvious Type Double Patenting
Appellant does not contest the provisional obviousness-type double
patenting rejection (Reply Br. 5). Therefore, we summarily affirm, and will
not further discuss, this rejection. See MANUAL OF PATENT EXAMINING
PROCEDURE § 1205.02 (“If a ground of rejection stated by the examiner is
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not addressed in the appellant's brief, that ground of rejection will be
summarily sustained by the Board.”)

SUMMARY
We reverse the rejection of claims 1, 4-8, 15-16, 19-20, 23-25, and
27-34 under 35 U.S.C. § 112, second paragraph, as being indefinite for
failing to particularly point out and distinctly claim the subject matter.
We affirm the rejection of claims 1, 4-8, 15-16, 19-20, 23-25, and 27-
34 under 35 U.S.C. § 103(a) as unpatentable over Carlson and
Constantinides.
We affirm the rejection of claims 1, 4-8, 15-16, 19-20, 23-25, and 27-
34 under 35 U.S.C. § 103(a) as unpatentable over Evans and Stergiopoulos.
We affirm the rejection of claims 1, 4-8, 15-16, 19-20, 23-25, and 27-
34 under 35 U.S.C. § 103(a) as unpatentable over Constantinides and
Stergiopoulos.
We affirm the rejection of claims 1, 4-8, 15-16, 19-20, 23-25, and 27-
34 on the ground of nonstatutory obviousness-type double patenting as being
unpatentable over claims 1-4, 15-28, and 35-44 of copending Application
No.10/497,775 by itself or in combination with Constantinides.

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).

AFFIRMED
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