Ex Parte Keller et al

Patent Trial and Appeal Board

Jan 13, 2015

12006820 (P.T.A.B. Jan. 13, 2015)

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.
12/006,820 01/04/2008 Brian Charles Keller EQUA-001 7196
7590 01/13/2015
Lee Pederson
712 East Main Street
Sleepy Eye, MN 56085
EXAMINER
KISHORE, GOLLAMUDI S
ART UNIT PAPER NUMBER
1612
MAIL DATE DELIVERY MODE
01/13/2015 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 BRIAN CHARLES KELLER and NIAN WU
__________

Appeal 2012-007324
Application 12/006,820
Technology Center 1600
__________

Before JEFFREY N. FREDMAN, ULRIKE W. JENKS, and
CHRISTOPHER G. PAULRAJ, Administrative Patent Judges.

FREDMAN, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal1 under 35 U.S.C. § 134 involving claims to a method
of treating or preventing a fungal infection. The Examiner rejected the
claims as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We affirm.

1 Appellants identify the Real Party in Interest as BioZone
Pharmaceuticals, Inc. (see App. Br. 3).
Appeal 2012-007324
Application 12/006,820

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Statement of the Case
Background
“Tetrahydrofuran antibiotics are widely used as antifungal agents . . .
[t]he newer tetrahydrofurans include posaconazole and itraconazole” (Spec.
2 ¶ 2). The Specification teaches that the “invention relates to drug delivery,
particularly to delivery of tetrahydrofuran antifungal agents by
microencapsulation and liposomal formulation” (Spec. 2 ¶ 1).
The Claims
Claims 17–24 are on appeal. Independent claim 17 is representative
and reads as follows:
17. A method of treating or preventing a fungal infection
comprising selecting a tetrahydrofuran drug; selecting a
diacylglycerol PEG lipid having a melting temperature
below about 25 degrees C and having packing parameters
favorable for the formation of liposomes; combining the
drug with the lipid in an aqueous solution; and administering
the solution.

The Issues
A. The Examiner rejected claims 17–22 under 35 U.S.C. § 103(a) as
being obvious over Lucchetti2 and Keller3 (Ans. 5).
B. The Examiner rejected claims 17–24 under 35 U.S.C. § 103(a) as
being obvious over Illum,4 McLean,5 MacLachlan,6 and Keller (Ans. 6–7).

2 Lucchetti et al., WO 93/15719 A1, published Aug. 19, 1993.
3 Keller et al., US 6,610,322, B1, issued Aug. 26, 2003.
4 Illum et al., US 2002/0025337 A1, published Feb. 28, 2002.
5 McLean et al., US 2003/0235610 A1, published Dec. 25, 2003.
6 MacLachlan et al., US 2006/0051405 A1, published Mar. 9,
2006.
Appeal 2012-007324
Application 12/006,820

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A. 35 U.S.C. § 103(a) over Lucchetti and Keller
The Examiner finds that Lucchetti teaches “liposomal itraconazole
formulations for the treatment of fungal infections . . . . The liposomes
however, are not made with PEG lipids” (Ans. 5).
The Examiner finds that Keller teaches
[L]iposomal formulation containing anti-infectives and the
same PEG-lipids. According to Keller, liposomal
suspensions are not thermodynamically stable, they are
trapped into higher energy states by the energy used in their
formation and they have the problems such as aggregation,
leakage, fusion associated with liposomal material. Further
according to Keller liposomes made with instant PEG-lipids
do not have these problems and liposomes are formed
spontaneously

(Ans. 5). The Examiner finds it obvious to “use liposomes of
Keller in the method of treatment of WO 93 because of the advantages
taught by Keller” (Ans. 5).
The issue with respect to this rejection is: Does the evidence of record
support the Examiner’s conclusion that the combination of Lucchetti and
Keller render claim 17 obvious?
Findings of Fact
1. Lucchetti teaches “a topical liposomal formulation comprising
itraconazole, a phospholipid, a solvent system for itraconazole and said
phospholipid, water and conventional auxiliary formulating agents, and a
method of preparing said formulation” (Lucchetti 1, ll. 10–12).
2. Lucchetti teaches that the “liposomal itraconazole formulation
penetrates rapidly and deeply in epithelial tissues and shows excellent
Appeal 2012-007324
Application 12/006,820

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retention of the active ingredient therein. The efficacy of the composition
for treating topical fungal infections is superb” (Lucchetti 1, ll. 25–27).
3. Keller teaches that “[l]iposomes are self-closed colloidal
particles in which membranes composed of one or more lipid bilayer(s)
encapsulate a fraction of the aqueous solution in which they are suspended. .
. . Their ability to incorporate many types of molecules has resulted in
applications for drug delivery” (Keller, col. 1, ll. 12–23).
4. Keller teaches that “[m]ost, if not all, known liposome
suspensions are not thermodynamically stable. Instead, the liposomes in
known suspensions are kinetically trapped into higher energy states by the
energy used in their formation” (Keller, col. 2, ll. 62–65).
5. Keller teaches that “known liposome formulations experience
problems with aggregation, fusion, sedimentation and leakage of liposome
associated material. A thermodynamically stable liposome formulation
which could avoid some of these problems is therefore desirable” (Keller,
col. 3, ll. 1–5).
6. Keller “teaches liposome suspensions which are
thermodynamically stable at the temperature of formation. The formulation
of such suspensions is achieved by employing a composition of lipids
having several fundamental properties . . . the lipid should include
polyethyleneglycol (PEG)” (Keller, col. 3, ll. 6–13).
7. Keller teaches a “liposome suspension forms spontaneously
upon adding a diacylglycerol-PEG lipid to an aqueous solution when the
lipid has appropriate packing parameters and the adding occurs above the
melting temperature of the lipid” (Keller, abstract).
Appeal 2012-007324
Application 12/006,820

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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).
Analysis
We adopt the Examiner’s findings of fact and reasoning regarding the
scope and content of the prior art (Ans. 5; FF 1–7) and agree that the claims
are obvious over Lucchetti and Keller. We address Appellants’ arguments
below.
Appellants contend that
[T]he examiner has done nothing but rely on a merely
conclusory statement. Examples 1 through 4 on pages 11-15
of the application as filed describe a series of experiments
that resulted in the claimed invention. The experimental
designs were created by the inventors out of a myriad of
potential experimental designs, and the results of the
experiments were in no way predictable based on the prior
art. The examiner dismisses this endeavor of discovery as
the “routine experimentation an artisan” and uses this
explanation as the basis of the current rejection. This is
clearly improper under the MPEP.

(App. Br. 7.)
We are not persuaded. Lucchetti teaches a method of treating a fungal
infection with the tetrahydrofuran drug, itraconazole, in a liposome (FF 1–
2). Keller teaches that forming more thermodynamically stable liposomes
by the addition of diacylglycerol-PEG is desirable to avoid aggregation,
fusion, sedimentation and leakage of liposome associated material (FF 3–6).
We agree with the Examiner that the person of ordinary skill would have
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Application 12/006,820

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reasonably been motivated to modify Lucchetti’s liposomes containing
itraconazole for treatment of fungal infections with the diacylglycerol-PEG
of Keller in order to obtain Keller’s specifically disclosed advantages of
avoiding aggregation, fusion, sedimentation and leakage of liposome
associated material (FF 5).
We also find Appellants unpredictability argument unpersuasive.
Appellants Examples 1–11 provide no evidence suggesting any
unpredictability in combining diacylglycerol-PEG into itraconazole
containing liposomes (see Spec. 11–23). In the absence of any
unpredictability, we conclude that there would be at least a reasonable
expectation that the ordinary artisan would have been able to successfully
apply Keller’s modifications of liposomes with diacylglycerol-PEG (FF 3–7)
to Lucchetti’s fungal treatment using liposomes containing itraconazole (FF
1–2) for the benefits taught by Keller (FF 5). Kubin stated that,
“[r]esponding to concerns about uncertainty in the prior art influencing the
purported success of the claimed combination, this court [in O’Farrell]
stated: ‘[o]bviousness does not require absolute predictability of success . . .
all that is required is a reasonable expectation of success.”’ In re Kubin,
561 F.3d 1351, 1360 (Fed. Cir. 2009) (citing In re O’Farrell, 853 F.2d 894,
903-904 (Fed. Cir. 1988)).
Conclusion of Law
The evidence of record supports the Examiner’s conclusion that the
combination of Lucchetti and Keller render claim 17 obvious.
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Application 12/006,820

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B. 35 U.S.C. § 103(a) over Illum, McLean, MacLachlan, and Keller
The Examiner finds that “Illum teaches liposomal preparations
containing itraconazole for the anti-fungal treatment . . . . McLean discloses
liposomal formulations containing anti-fungal agents . . . . Similarly Mac
Lachlan teaches liposomal formulations containing anti-fungal agents such
as itraconazole” (Ans. 6). The Examiner acknowledges that the “liposomes
however, are not made with PEG lipids” (Ans. 6).
The Examiner relies upon Keller as discussed above (see Ans. 6). The
Examiner finds it obvious “to use liposomes of Keller in the method of
treatment of Illum, McLean and Mac Lachlan [sic] because of the
advantages taught by Keller” (Ans. 6).
The issue with respect to this rejection is: Does the evidence of record
support the Examiner’s conclusion that the combination of Illum, McLean,
MacLachlan, and Keller render claim 17 obvious?
Findings of Fact
8. Illum teaches that “[d]rugs can be administered by a variety of
routes to include oral and parenteral. It is often useful to have available an
injectable form of a drug in order to provide rapid onset of action” (Illum 1 ¶
2).
9. Illum teaches that “[d]rugs that are especially suitable for the
emulsion formulation are antifungal agents such as itraconazole” (Illum 4 ¶
34).
10. Example 1 of Illum teaches a liposome composed of
phospholipid, Vitamin E, water, and itraconazole (Illum 6 ¶ 66).
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Application 12/006,820

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11. McLean teaches “methods of treating . . . fungal . . . infections.
The methods involve topically, externally, or internally applying a liposome
composition . . . the infection can be a fungal infection treated by applying a
composition to the infected area” (McLean 2 ¶ 14).
12. MacLachlan teaches that:
For the delivery of therapeutic or bioactive agents, the PEG-
lipid-containing liposome compositions can be loaded with a
therapeutic agent and administered to the subject requiring
treatment. The therapeutic agents which are administered
using the compositions and methods of the present invention
can be any of a variety of drugs that are selected to be an
appropriate treatment for the disease to be treated. . . .
[including] antifungal agents, e.g., miconazole, terconazole,
econazole, isoconazole, butaconazole, clotrimazole,
itraconazole, nystatin, naftifine and amphotericin B.

(MacLachlan 20 ¶ 234.)
13. MacLachlan teaches “lipid-based carrier systems containing
polyethyleneglycol (PEG)-lipid conjugates, e.g., . . . PEG-diacylglycerol
(DAG) conjugates” (MacLachlan 7 ¶ 81).
Analysis
We adopt the Examiner’s findings of fact and reasoning regarding the
scope and content of the prior art (Ans. 6; FF 3–13) and agree that the claims
are obvious over Illum, McLean, MacLachlan, and Keller. We address
Appellants’ arguments below.
Appellants contend that “the examiner ignores the research findings
[of the] inventors, ignores the specific claim limitations arising from the
research findings, and concludes that slapping a couple references together
render the unexpected results obvious” (App. Br. 8).
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Application 12/006,820

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We are not persuaded. The Examiner has relied upon specific prior
art references which specifically teach each of the limitations of the rejected
claims, and particularly teach treatment of fungal infections (FF 9, 11) using
drugs such as itraconazole (FF 10, 12) in combination with diacylglycerol
PEG (FF 7, 13) because Keller teaches that forming more
thermodynamically stable liposomes by the addition of diacylglycerol-PEG
is desirable to avoid aggregation, fusion, sedimentation and leakage of
liposome associated material (FF 3–7). Appellants do not identify any
specific claim limitations which the Examiner failed to address, nor any
unexpected results.
Conclusion of Law
The evidence of record supports the Examiner’s conclusion that the
combination of Illum, McLean, MacLachlan, and Keller render claim 17
obvious.
SUMMARY
In summary, we affirm the rejection of claim 17 under 35 U.S.C.
§ 103(a) as being obvious over Lucchetti and Keller. Pursuant to 37 C.F.R.
§ 41.37(c), claims 18–22 fall with claim 17, as these claims were not argued
separately.
We affirm the rejection of claim 17 under 35 U.S.C. § 103(a) as being
obvious over Illum, McLean, MacLachlan, and Keller. Pursuant to
37 C.F.R. § 41.37(c), claims 18–24 fall with claim 17, as these claims were
not argued separately.

Appeal 2012-007324
Application 12/006,820

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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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