Ex Parte Berndl et al

Board of Patent Appeals and Interferences

May 27, 2010

10296451 (B.P.A.I. May. 27, 2010)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
____________

Ex parte GUNTHER BERNDL, JORG BREITENBACH,
ROBERT HEGER, MICHAEL STADLER, PETER WILKE, and
JORG ROSENBERG
____________

Appeal 2009-014075
Application 10/296,451
Technology Center 1600
____________

Decided: May 27, 2010
____________

Before ERIC GRIMES, DONALD E. ADAMS, and STEPHEN WALSH,
Administrative Patent Judges.

ADAMS, Administrative Patent Judge.

DECISION ON APPEAL
This appeal under 35 U.S.C. § 134 involves claims 16-18 and 20-38,
the only claims pending in this application. We have jurisdiction under 35
U.S.C. § 6(b).

Appeal 2009-014075
Application 10/296,451

STATEMENT OF THE CASE
The claims are directed to a self-emulsifying formulation. Claims 16
and 31 are illustrative:
16. A self-emulsifying formulation comprising
i) 0.1 to 50% by weight of an active ingredient component comprising
at least one active ingredient, and having a content of active ingredient
crystals of less than 5%;
ii) 6 to 60% by weight of a lipid component comprising at least one
lipid, and having a melting point not exceeding 50ºC;
iii) 20 to 93.9% by weight of a binder component comprising one or
more binders selected from polyvinylpyrrolidones,
vinylpyrrolidone/vinylacetate copolymers, hydroxyalkylcelluloses,
hydroxyalkylalkylcelluloses, cellulose phthalates and (meth)acrylic resins;
and
iv) 0 to 30% by weight of at least one further excipient,
wherein the content of lipid component based on the binder component does
not exceed 40% by weight.

31. A self-emulsifying formulation comprising
i’) an active ingredient component comprising at least one essential
oil;
ii’) optionally another lipid component comprising at least one further
lipid;
iii’) a binder component comprising at least one binder which is
selected from polyvinylpyrrolidones, vinylpyrrolidone/vinylacetate
copolymers, hydroxyalkylcelluloses, hydroxyalkylalkylcelluloses, cellulose
phthalates and (meth)acrylic resins; and
iv’) optionally at least one further excipient,
wherein the content of the components i’) and ii’) based on the total weight
of the formulation is from 6 to 60% and the content of the components i’)
and ii’) based on the binder component does not exceed 40% by weight.

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The rejection presented by the Examiner follows:
Claims 16-18 and 20-381 stand rejected under 35 U.S.C. § 103(a) as
unpatentable over the combination of Lee,2 Piechota,3 Serajuddin,4
Rodriguez-Espinosa, 5 and Maul.6
We reverse the rejection of claims 16-18 and 20-30. We affirm the
rejection of claims 31-38, but designate the affirmance a new ground of
rejection.

Claims 16-18 and 20-30:
ISSUE
Does the preponderance of evidence on this record support the
Examiner’s conclusion that it would have been prima facie obvious to a
person of ordinary skill in the art to prepare a formulation as required by
Appellants’ claimed invention that has a content of active ingredient crystals
of less than 5%?

1 The “Status of the Claims” section of Appellants’ Brief states that claim 19
has been canceled (App. Br. 2). The Examiner states that “[t]he statement of
the status of claims contained in the brief is correct” (Ans. 2). Accordingly,
it appears that the Examiner incorrectly included cancelled claim 19 in the
statement of the rejection (Ans. 3). We find this to be a harmless
typographical error and have not considered claim 19 in our deliberations.
2 Lee, WO 00/00179, published Jan. 6, 2000.
3 Piechota et al., CA 1 270 201, issued Jun. 12, 1990.
4 Abu T. M. Serajuddin, Bioavailability enhancement of poorly water-
soluble drugs by solid dispersion in surface active and self-emulsifying
vehicles, JOURNEES GALENIQUES 43-50 (1997). While the Examiner refers
to this reference as “Abu” (see, e.g., Ans. 3-4), we will follow convention
and use the Author’s last name (Serajuddin) when referring to this reference.
5 C. Rodriguez-Espinosa, Dissolution kinetics for coprecipitates of diflunisal
with PVP K30, abstract, PubMed Identification No. 9725466.
6 Maul et al., US 6,274,727 B1, issued Aug. 14, 2001.
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FINDINGS OF FACT
FF 1. Lee’s Examples XI, XVII, and XXII teach a formulation comprising
10.5% by weight of an active ingredient (ketoconazole or cisapride), 5.3%
by weight of a lipid (oleic acid); and a binder (42.1% by weight of PEG
6000, 84.2% by weight of PEG 6000, and 84.2% by weight of PVP,
respectively) (Ans. 4).
FF 2. Piechota teaches a dentifrice composition that comprises a flavor oil
and PVP (Ans. 5).
FF 3. The Examiner finds that the combination of Lee and Piechota fails to
suggest a formulation wherein the content of active ingredient crystals is less
than 5% (id.).
FF 4. Serajuddin teaches that “[t]he most commonly used technique of
enhancing oral absorption and bioavailability of poorly water-soluble drugs
is to increase their dissolution rates” (Serajuddin 43: col. 1, ll. 1-4; Ans. 5).
In this regard, Serajuddin teaches that the “[r]eduction of particle size to as
low as the submicron range . . . leads to higher dissolution rate and higher
bioavailability of drugs” (Serajuddin 43: col. 2, ll. 10-14).
FF 5. Rodriguez-Espinosa “teaches a study about diflunisal which is a
nonsteroidal anti-inflammatory drug that is poorly soluble in water” (Ans.
6). Rodriguez-Espinosa teaches “that diflunisal is present in solid
dispersions in crystalline or amorphous state[s] depending on the PVP
content” (Ans. 6 and 11).
FF 6. Liepold7 prepared formulations corresponding to Lee’s Examples I,
XI, XIII, and XXII (Liepold Dec. 2: ¶ 6).

7 Liepold Declaration, executed December 20, 2005.

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FF 7. Liepold declares that “in the preparations described in . . . [Lee] a
considerable proportion of the active ingredients, ketoconazole and
itraconaxole, was present in crystalline form” (id.).
FF 8. Maul teaches “a composition, comprising one or more polyols,
which has prolonged deformability and can be processed to give tablets,
compacts or boiled sweets” (id.).

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). Nevertheless, “it
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.” KSR, 550 U.S. at 418.

ANALYSIS
The formulation of claim 16 requires, inter alia, an active ingredient
component, wherein the content of active ingredient crystals is less than 5%.
Claims 17, 18, and 20-30 depend directly or indirectly from claim 16.
The Examiner finds that the combination of Lee and Piechota fails to
suggest the requirement in Appellants’ claims 16-30 of an active ingredient
component, wherein the content of active ingredient crystals is less than 5%
(FF 3). The Liepold Declaration supports the Examiner’s findings (FF 7 and
8). Accordingly, the Examiner relies on Serajuddin and Rodriguez-
Espinosa to make up for this deficiency in the combination of Lee and
Piechota.
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The Examiner relies on Serajuddin to teach that a reduction in the
particle size of an active ingredient increases its dissolution rate and
provides for a higher bioavailability of the drug (FF 4). In response,
Appellants contend that “particle size reduction is not tantamount to a
reduction of the amount of crystals in a formulation” (App. Br. 13). We
agree. We recognize the Examiner’s reliance on two references, Serajuddin
II8 and Schwartz,9 newly cited in the Answer, to bridge the evidentiary gap
in the combination of Lee, Piechota, and Serajuddin (see Ans. 8 and 10).
These references, however, were not recited in the Examiner’s statement of
the rejection. Accordingly, we have not considered these references in our
deliberations. In re Hoch, 428 F.2d 1341, 1342 n.3 (CCPA 1970); Ex parte
Movva, 31 USPQ2d 1027, 1028 n.1 (BPAI 1993).
The Examiner relies on Rodriguez-Espinosa to teach that the
nonsteroidal anti-inflammatory drug diflunisal is present in solid dispersions
in a crystalline or amorphous state depending on the PVP content of the
formulation (FF 12). According to the Examiner, Rodriguez-Espinosa
“presents knowledge to people of ordinary skill in the art that PVP content in
solid dispersion is one of the factors that can control crystallinity of a drug
having poor-solubility” (Ans. 11). In response, Appellants contend that
Lee’s Example XXII has a PVP content of 84.2 % by weight, which is a
higher amount of PVP than is suggested by Rodriguez-Espinosa, yet a

8 Abu T.M. Serajuddin (Serajuddin II), Solid Dispersion of Poorly Water-
Soluble Drugs: Early Promises, Subsequent Problems, and Recent
Breakthroughs, 88 J. PHARMA. SCI. 1058-1066 (1999).
9 Joseph B. Schwartz Pharmaceutical Dosage Forms, Volume 2, 460-461
(Herbert A. Lieberman, et al., eds., Marcel Dekker, Inc., New York) (1990),
http://www.netlibrary.com/Reader/HighlightProxy.aspx?bookid=12702&lin
ks=solid,dispe. . . ., accessed February 21, 2009.
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considerable proportion of the active ingredients were present in crystalline
form (App. Br. 16; FF 7). The Examiner does not address Appellants’
contention. Instead, the Examiner simply concludes that “[i]t is the position
of the Examiner that the skilled artisan would be motivated to increase the
PVP to increase the solubility of a poorly soluble drug in a solid dispersion”
(Ans. 10-11). We are not persuaded. As Appellants explain, Lee’s
formulation already contains an increased amount of PVP relative to
Rodriguez-Espinosa.
Maul (FF 13) fails to make up for the deficiencies in the combination
of Lee, Piechota, Serajuddin, and Rodriguez-Espinosa (see App. Br. 12-13).

CONCLUSION OF LAW
The preponderance of evidence on this record fails to support the
Examiner’s conclusion that it would have been prima facie obvious to a
person of ordinary skill in the art to prepare a formulation as required by
Appellants’ claimed invention that has a content of active ingredient crystals
of less than 5%.
The rejection of claims 16-18 and 20-30 under 35 U.S.C. § 103(a) as
unpatentable over the combination of Lee, Piechota, Serajuddin, Rodriguez-
Espinosa, and Maul is reversed.

Claims 31-38:
ISSUE
Does the preponderance of evidence on this record suggest a self-
emulsifying formulation comprising an essential oil component, a lipid
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component, and a binder; wherein the combined amount of the essential oil
and lipid components (1) is from 6 to 60% by weight of the composition and
(2) does not exceed 40% by weight of the amount of binder component?

FINDINGS OF FACT
FF 9. Lee teaches a formulation comprising an active ingredient (a drug); a
binder (e.g., polyvinyl pyrrolidone (PVP)); and oils, fatty acids, or mixtures
thereof (e.g., oleic acid, Perilla extract, and peach (Prunus persica) leaf
extract) (Ans. 4; Lee 2: 17-23, 6: 8-15, 7: 12-13, and 7: 17-22).
FF 10. Lee exemplifies a formulation comprising 10.5% by weight of an
active ingredient (ketoconazole), 5.3% by weight of a lipid (oleic acid), and
84.2% by weight of a binder (PVP) (Lee 29: 15-21 (Example XXII)).
FF 11. Appellants’ Specification discloses that “the term ‘essential oil’
means mixtures of substances which are obtainable from plant raw materials
by steam distillation” (Spec. 6: 12-14).
FF 12. Essential oils within the scope of the claimed invention include
lemon oil, peppermint oil, and cinnamon oil (Spec. 5: 6-41).
FF 13. Piechota teaches a dentifrice composition that comprises PVP and an
essential oil such as peppermint, cinnamon, or lemon at a concentration of
about 0.01 to 5% by weight of the composition (Ans. 5; Piechota Abstract
and 7: 16-21).

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). It is proper to “take
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account of the inferences and creative steps that a person of ordinary skill in
the art would employ.” Id. at 418. See also id. at 421 (“A person of
ordinary skill is also a person of ordinary creativity, not an automaton.”). In
sum, the “suggestion test is in actuality quite flexible and not only permits,
but requires, consideration of common knowledge and common sense.”
DyStar Textilfarben GmbH & Co. Deutschland KG v. C.H. Patrick Co., 464
F.3d 1356, 1367 (Fed. Cir. 2006). In this regard, “[w]here the general
conditions of a claim are disclosed in the prior art, it is not inventive to
discover the optimum or workable ranges by routine experimentation.” In re
Aller, 220 F.2d 454, 456 (1955).

ANALYSIS
The claims have not been argued separately and therefore stand or fall
together. 37 C.F.R. § 41.37(c)(1)(vii). Claim 31 is representative and
requires, inter alia, that the content of the essential oil and lipid components
of the formulation is from 6 to 60% by weight. Claims 32-38 depend
directly or indirectly from claim 31.
Lee teaches a formulation comprising 10.5% by weight of an active
ingredient, 84.2 % by weight of a binder, and 5.3% by weight of a lipid (FF
9 and 10). Lee teaches that an oil may be used in place of a lipid (e.g., fatty
acid) or alternatively that a mixture of oil and fatty acid can be used (FF 9).
Accordingly, based on the teachings of Lee, it would have been prima facie
obvious to substitute an oil or mixture of an oil and lipid for the lipid
component of Lee’s exemplified formulations (see FF 10).
Lee teaches that the oil may be, inter alia, peach leaf extract (FF 9).
Appellants define an essential oil as “mixtures of substances which are
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obtainable from plant raw materials by steam distillation” (FF 11). There is
no evidence on this record to suggest that peach leaf extract is not an
essential oil as defined by Appellants. Further, Piechota teaches that
essential oils, useful in combination with PVP, that fall within the scope of
Appellants’ claimed invention and were known in the art at the time
Appellants’ invention was made (Cf. FF 12 and 13). Accordingly, we find
that it would have been prima facie obvious to have utilized essential oils,
such as peppermint, cinnamon, and lemon as set forth in Piechota, in Lee’s
formulation.
In Lee’s exemplified formulation the content of the oils, fatty acids, or
mixtures thereof based on the binder component does not exceed 40% by
weight.
Lee’s composition, however, comprises 0.7% less oil or mixture of oil
and lipid than is required by Appellants’ claim 31. The question, then, is
whether it would have been prima facie obvious to a person of ordinary skill
in this art at the time the invention was made to discover the optimum or
workable range of oil in Lee’s formulation by routine experimentation.
Given the evidence on this record, which set forth the general conditions of
the claimed composition, we are compelled to answer this question in the
affirmative. Aller, 220 F.2d at 456. Accordingly, we find that it would have
been prima facie obvious to a person of ordinary skill in this art to include
0.7% more oil in the composition set forth in Lee’s Example XXII (see FF
10).
Appellants contend that Serajuddin and Rodriguez-Espinosa “do not
address preparations which comprise essential oils or other lipids” (App. Br.
18). We agree and find that neither reference compels a conclusion that the
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invention of claim 31 would not have been prima facie obvious to a person
of ordinary skill in this art at the time the invention was made.
Appellants contend that Piechota teaches “dentifrices [that] comprise
even less oil component than the representative solid preparations of Lee . . .
[and] therefore, cannot be deemed to provide a person having ordinary skill
in the pertinent art with a motivation to increase the amount of the oil
component of Lee’s preparation” (id. (emphasis removed)). We are not
persuaded. Piechota teaches compositions comprising 1% less of an
essential oil than is required by Appellants’ claimed invention (see FF 13).
For the reasons set forth above, we are compelled to find that “it is not
inventive to discover the optimum or workable ranges by routine
experimentation.” Aller, 220 F.2d at 456.
Appellants contend that Maul teaches that “glycerides of fatty acids
and lecithins . . . are generally not needed in preparations based on polyols”
(App. Br. 18). While this may be true, Appellants have failed to explain
why this disclosure in Maul is relevant to a composition comprising an
active agent, an essential oil, and PVP as suggested by the combination of
references relied upon by the Examiner.
In sum, we find that claim 31 is prima facie obvious in view of the
combination of Lee and Piechota.
We recognize and agree with Appellants’ contention that “[t]he
Examiner did not provide separate arguments why the subject matter of
Claim 31 was deemed to be rendered prima facie obvious by the referenced
art” (App. Br. 17). Accordingly, we designate our affirmance a new ground
of rejection.

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CONCLUSION OF LAW
The preponderance of evidence on this record suggests a self-
emulsifying formulation comprising an essential oil component, a lipid
component, and a binder; wherein the combined amount of the essential oil
and lipid components (1) is from 6 to 60% by weight of the composition and
(2) does not exceed 40% by weight of the amount of binder component.
The rejection of claim 31 under 35 U.S.C. § 103(a) as unpatentable
over the combination of Lee, Piechota, Serajuddin, Rodriguez-Espinosa, and
Maul is affirmed. Claims 32-38 fall together with claim 31.

TIME PERIOD FOR RESPONSE
This decision contains a new ground of rejection pursuant to 37
C.F.R. § 41.50(b) (effective September 13, 2004, 69 Fed. Reg. 49960
(August 12, 2004), 1286 Off. Gaz. Pat. Office 21 (September 7, 2004)). 37
C.F.R. § 41.50(b) provides “[a] new ground of rejection pursuant to this
paragraph shall not be considered final for judicial review.”
37 C.F.R. § 41.50(b) also provides that the Appellant, WITHIN TWO
MONTHS FROM THE DATE OF THE DECISION, must exercise one of
the following two options with respect to the new ground of rejection to
avoid termination of the appeal as to the rejected claims:
(1) Reopen prosecution. Submit an appropriate amendment of
the claims so rejected or new evidence relating to the claims so
rejected, or both, and have the matter reconsidered by the
examiner, in which event the proceeding will be remanded to
the examiner….

(2) Request rehearing. Request that the proceeding be reheard
under § 41.52 by the Board upon the same record….

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AFFIRMED-IN-PART, 37 C.F.R. § 41.50(b)

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