Ex Parte Spilburg

Patent Trial and Appeal Board

Oct 24, 2012

11291126 (P.T.A.B. Oct. 24, 2012)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte CURTIS A. SPILBURG
__________

Appeal 2011-002786
Application 11/291,126
Technology Center 1600
__________

Before JEFFREY N. FREDMAN, STEPHEN WALSH, and
JACQUELINE WRIGHT BONILLA, Administrative Patent Judges.

FREDMAN, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a solid
anhydrous drug delivery composition. The Examiner rejected the claims as
obvious. We have jurisdiction under 35 U.S.C. § 6(b). We affirm.

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Statement of the Case
Background
“This invention relates to a general method for enhancing the
bioavailability of hydrophobic drug active compounds, using naturally-
occurring formulation ingredients that are present in the diet” (Spec. 1, ll.
11-13). According to the Specification, the “formulation method described
contains a minimum of three components, an emulsifier(s), a sterol and a
hydrophobic active or drug compound” (Spec. 7, ll. 30-31).
The Claims
Claims 1-6, 8, 9, and 28-30 are on appeal. Independent claim 1 is
representative and reads as follows:
1. A solid, anhydrous drug delivery composition for
normally difficultly soluble hydrophobic drug actives, which
when added to water creates suspended liposomes having a
mean particle size of at least 1.0 microns, comprising:
an amphiphile or emulsifier;
a sterol;
a drug active effective amount of a hydrophobic drug
with the weight ratio of said amphiphile or emulsifier to the
sterol and drug active combination being less than 3.0 and
greater than 0.05.

The issue
1

The Examiner rejected claims 1-6, 8, 9, and 28-30 under 35 U.S.C. §
103(a) as obvious over Orthoefer
2
(Ans. 4-8).

1
The Examiner did not restate the § 112 rejections from the Final
Office action in the Examiner‟s Answer. We consider these
rejections to have been withdrawn by the Examiner.
2
Orthoefer, F., WO 00/45770 A2, published Aug. 10, 2000.
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The Examiner finds that in “one example, Orthoefer teaches a
formulation comprising 33% plant sterols and 67% powdered
phospholipids” (Ans. 4). The Examiner finds that “Orthoefer suggests that
the amount of phospholipids added is equal to between 20% and 100% of
the total composition . . . and that other additives are present in an amount of
0.01 % to 80% by weight of the total composition” (Ans. 4). The Examiner
finds that “Orthoefer suggests the inclusion of drugs such as HMG-CoA
reductase inhibitors (statins) including fluvastatin” (Ans. 4). The Examiner
finds that the “composition of Orthoefer is described as a pro-liposome in an
extruded tablet form, which is converted into a liposome when hydrated by
water in the small intestine” (Ans. 4).
The Examiner finds it obvious to “have selected various combinations
of various disclosed ingredients specifically phospholipids, a sterol, and a
drug from within a prior art disclosure” (Ans. 6). The Examiner finds that
“Orthoefer does not explicitly teach that the composition forms liposomes of
a particle size of at least 1.0 microns . . . However, the prior art
compositions appear to be substantially the same as those of the claims, and
as such, would be expected to have the same properties” (Ans. 6).
Appellant contends that “Orthoefer fails to show Applicant[‟]s
liposomes, fails to show a mean particle size of greater than 1 micron, and
fails to show the ratio of emulsifier to sterol plus drug, being less than 3.0
and greater than .05” (App. Br. 3).
Appellant contends that the “specification and the example in
Applicant‟s description taken together demonstrate the essential nature of
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these limits for providing bioavailability of difficultly soluble hydrophobic
drugs in order to provide consistent pharmacologic responses” (App. Br. 6).
Appellant contends that “Applicant has discovered a system to allow
normally difficultly soluble drugs to be made bioavailable in pill form, a
much preferred delivery form, not previously available to obtain predictable,
sustained pharmaceutical affect” (App. Br. 7). Appellant contends that in
“the absence of any articulated logical reasoning as to why, this cannot be
successfully argued as obvious to one of ordinary skill in the art” (App. Br.
7).
The issue with respect to this rejection is: Does the evidence of
record support the Examiner‟s conclusion that Orthoefer renders claim 1
obvious?
Findings of Fact
1. Orthoefer teaches in Example 12 that:
Oral LCP tablets similar to the tablets discussed in Example
8 were prepared, but in place of a portion of the
phospholipid, 33% by weight of plant sterols were mixed
with 67% powdered phospholipid in a commercial grade
mixer. The phospholipid- sterol preparation was extruded in
an APV Baker model MPF 50 extruder at a pressure of 850
psig and exited the die as a continuous, smooth-feeling rope
which was cut into dosage units of 400 milligrams each.
These extruded tablets developed a hard texture upon
cooling suitable for an orally administered dosage form. The
product of this Example were consumed to reduce the
cholesterol in the blood.

(Orthoefer 24, l. 15 to 25, l. 2).

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2. Orthoefer teaches in Example 17 that:
A study was performed to compare the effects of cholesterol
reduction using the 2% LCP alone, .01% Lescol (a HMG
CoA reductase inhibitor) alone, and a combination of .01 %
Lescol mixed with the phospholipids and extruded to create
the LCP. The dosage was administered to Golden Syrian
hamsters which were bled after two weeks to determine the
cholesterol lowering effects. Table 3 shows that the LCP and
Lescol act additively to reduce the serum cholesterol levels.

(Orthoefer 27, l. 19, to 28, l. 2).
3. Orthoefer teaches that the “solid LCP composition is made by
placing a desirable amount of the phospholipids in a means for compressing
the powdered or granular phospholipid. The amount of the phospholipids
added is equal to between about 20% and 100%, or preferably from 30% to
100% by weight of the LCP composition” (Orthoefer 14, ll. 16-19).
4. Orthoefer teaches that an “amount of an additive can be placed
in the pressure means with the powdered phospholipid, with the additive or
additives added in an amount equal to between 0.01% by weight and about
80% by weight of the total solid LCP composition” (Orthoefer 15, ll. 15-18).
5. Orthoefer teaches that a “variety of additives can be mixed with
the powdered phospholipid to form said LCP compositions, including . . .
herbal extracts, essential fatty acids, drugs, phytochemicals” (Orthoefer 15,
ll. 18-21).
6. Orthoefer teaches that the “phospholipid tablet can also contain
pharmaceutical constituents which are desirable for oral administration, such
as . . . HMG-CoA reductase inhibitors are prescribed for those persons who
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suffer from high plasma cholesterol levels and the consequential threat of
cardiovascular disease” (Orthoefer 16, ll. 1-6).
7. Orthoefer teaches “a solid phospholipid composition which
may contain active ingredients for oral ingestion in extruded tablet form,
which tablets are pro-liposomes that are converted into liposomes when they
are hydrated by water in the small intestine” (Orthoefer 10, ll. 9-12).
8. The Examiner finds that the “combination of the drug from
Example 17 and the plant sterols from Example 12 would have resulted in a
composition with a weight ratio of phospholipids to the combination of
sterol and drug of close to 2, which is within the range of claim 1” (Ans. 6).
9. The Specification teaches, regarding the prior art methods
disclosed in pages 2 and 3 of the Specification, that the “goal of all these
methods is to produce a solid that can be re-hydrated at a later time to form
liposomes that can deliver a biologically active substance to a target tissue or
organ” (Spec. 3, ll. 32-34).
10. The Specification teaches that:
the goal is to produce an emulsified mixture of drug, sterols
and amphiphile that has a mean particle size of at least 1.0
µm. To achieve this end, the amount of amphiphile in the
system is minimized relative to the other two components so
that the ratio of amphiphile to the drug sterol combination is
3.0 or less. On the other hand, sufficient amphiphile must be
present to allow emulsification such that the ratio of
amphiphile to the sterol drug combination is 0.05 or greater.

(Spec. 9, ll. 23-29).
11. The Specification teaches that a “preferred emulsifier is
lecithin” (Spec. 8, l. 1).
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12. The Specification teaches that “[p]lant-derived sterols,
especially those derived from soy and tall oil, are the preferred choice”
(Spec. 8, ll. 22-23).
13. The Specification teaches that “potential drugs may be selected
from any therapeutic class including but not limited to . . . cardiovascular
agents” (Spec. 8, l. 35 to 9, l. 3).
14. The Specification teaches that the “solid material so prepared
can then be compressed at elevated pressure and extruded into a rope. The
rope can be cut in segments to form tablets” (Spec. 10, ll. 9-11).
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). “If a person of
ordinary skill can implement a predictable variation, § 103 likely bars its
patentability.” Id. at 417.
Once a prima facie case of obviousness has been established, the
burden shifts to the Appellant to prove that the prior art product does not
necessarily or inherently possess the characteristics of the claimed product.
In re Best, 562 F.2d 1252, 1255 (CCPA 1977) (“Where, as here, the claimed
and prior art products are identical or substantially identical, or are produced
by identical or substantially identical processes, the PTO can require an
applicant to prove that the prior art products do not necessarily or inherently
possess the characteristics of his claimed product.”).

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Analysis
Orthoefer teaches in Example 12 that “[o]ral LCP tablets . . . were
prepared . . . 33% by weight of plant sterols were mixed with 67% powdered
phospholipid in a commercial grade mixer. . . .The product of this Example
were consumed to reduce the cholesterol in the blood” (Orthoefer 24, l. 15 to
25, l. 2; FF 1). Orthoefer teaches that the “phospholipid tablet can also
contain pharmaceutical constituents which are desirable for oral
administration, such as . . . HMG-CoA reductase inhibitors . . . for those
persons who suffer from high plasma cholesterol levels and the
consequential threat of cardiovascular disease” (Orthoefer 16, ll. 1-6; FF 6).
In Example 17, Orthoefer compared “the effects of cholesterol reduction
using the 2% LCP alone, .01% Lescol (a HMG CoA reductase inhibitor)
alone, and a combination of .01 % Lescol mixed with the phospholipids . . .
Table 3 shows that the LCP and Lescol act additively to reduce the serum
cholesterol levels” (Orthoefer 27, l. 19, to 28, l. 2; FF 2).
Applying the KSR standard of obviousness to the findings of fact, we
conclude that the person of ordinary skill would have modified Orthoefer‟s
cholesterol lowering formulation of Example 12 to further incorporate an
HMG-CoA reductase inhibitor additive since Orthoefer teaches that
inclusion of the HMG-CoA reductase inhibitor acts additively with the LCP
to reduce cholesterol in blood (FF 1-6). Such a combination is merely a
“predictable use of prior art elements according to their established
functions.” KSR, 550 U.S. at 417.
Appellant contends that “Orthoefer fails to show Applicant[‟]s
liposomes, fails to show a mean particle size of greater than 1 micron, and
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fails to show the ratio of emulsifier to sterol plus drug, being less than 3.0
and greater than .05” (App. Br. 3).
We are not persuaded, and will address these three points separately.
Addressing the issue of liposomes, Orthoefer teaches “a solid phospholipid
composition which may contain active ingredients for oral ingestion in
extruded tablet form, which tablets are pro-liposomes that are converted into
liposomes when they are hydrated by water in the small intestine” (Orthoefer
10, ll. 9-12; FF 7). Thus, Orthoefer directly teaches that the tablets form
liposomes in the small intestine (FF 7). This is consistent with Appellant‟s
own Specification, which discusses liposome methods on pages 2 and 3,
specifically discussing Orthoefer and concluding that the “goal of all these
methods is to produce a solid that can be re-hydrated at a later time to form
liposomes that can deliver a biologically active substance to a target tissue or
organ” (Spec. 3, ll. 32-34; FF 9). Thus, the weight of the evidence presented
supports the Examiner‟s finding that Orthoefer‟s tablets result in liposome
formation when hydrated by water (FF 7, 9).
Addressing Appellant‟s ratio argument next, the Examiner finds that
the “combination of the drug from Example 17 and the plant sterols from
Example 12 would have resulted in a composition with a weight ratio of
phospholipids to the combination of sterol and drug of close to 2, which is
within the range of claim 1” (Ans. 6; FF 8). That is, Example 12 uses 67 %
phospholipid, 33% sterols and Example 17 adds only 0.01% drug, so that the
weight ratio of phospholipid to sterol + drug would be roughly 2:1, falling
within the 0.05:1 to 3:1 ratio required by claim 1 (FF 1-2, 8). This directly
satisfies the requirements of claim 1.
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Lastly, regarding Appellant‟s second point about the 1 micron mean
particle size, the Examiner finds that “the prior art compositions appear to be
substantially the same as those of the claims, and as such, would be expected
to have the same properties” (Ans. 6). The Examiner‟s inherency argument
is consistent with the evidence of record. That is, the Specification teaches
that to achieve a mean particle size of 1 micron, a ratio of phospholipid to
sterol and drug within a 0.05:1 to 3:1 ratio is required (FF 10). The
Specification also requires an emulsifier where lecithin is preferred (FF 11),
a sterol where plant sterols are preferred (FF 12), and a drug which may
include cardiovascular agents (FF 13).
Orthoefer teaches a composition with a 2:1 ratio of lecithin to plant
sterols and suggests inclusion of a small amount of a cardiovascular agent,
lescol, as an additive for cooperative effects with the lecithin (FF 1, 2, 4-6).
Orthoefer‟s obvious composition is structurally identical to the preferred
composition of the Specification (FF 10-13) and would therefore reasonably
be expected to have the same inherent properties of the composition of the
Specification, including a mean particle size of 1 micron. As noted in Best,
“[w]here, as here, the claimed and prior art products are identical or
substantially identical, or are produced by identical or substantially identical
processes, the PTO can require an applicant to prove that the prior art
products do not necessarily or inherently possess the characteristics of his
claimed product. . . . Whether the rejection is based on „inherency‟ under 35
U.S.C. § 102, on „prima facie obviousness‟ under 35 U.S.C. § 103, jointly or
alternatively, the burden of proof is the same, and its fairness is evidenced
by the PTO‟s inability to manufacture products or to obtain and compare
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prior art products” In re Best, 562 F.2d 1252, 1255 (CCPA 1977). On this
record, Appellant has proffered no evidence or proof that Orthoefer‟s
obvious composition, composed of identical reagents in identical amounts to
those claimed, does not inherently satisfy the 1 micron liposome requirement
(FF 7).
Appellant contends that the “specification and the example in
Applicant‟s description taken together demonstrate the essential nature of
these limits for providing bioavailability of difficultly soluble hydrophobic
drugs in order to provide consistent pharmacologic responses” (App. Br. 6).
We are not persuaded. In fact, the Specification provides no evidence
that the composition of claim 1 differs in any material way from the obvious
composition of Orthoefer, and the evidence of record supports the
Examiner‟s reliance on the inherency doctrine (FF 1-13).
Appellant contends that “Applicant has discovered a system to allow
normally difficultly soluble drugs to be made bioavailable in pill form, a
much preferred delivery form, not previously available to obtain predictable,
sustained pharmaceutical affect” (App. Br. 7). Appellant contends that in
“the absence of any articulated logical reasoning as to why, this cannot be
successfully argued as obvious to one of ordinary skill in the art” (App. Br.
7).
We are not persuaded. The Examiner reasonably relies upon
Orthoefer, particularly examples 12 and 17, where example 12 teaches a
lecithin/sterol composition which differs from the claim only in the absence
of a drug, and teaches that the composition reduces cholesterol levels in
blood. Example 17 teaches inclusion of a drug which reduces cholesterol
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levels in blood and teaches that the drug works additively with a lecithin
composition to achieve cholesterol lowering effects. We agree with the
Examiner that it would have been obvious to incorporate the cholesterol
lowering drug of example 17 into the cholesterol lowering lecithin/sterol
composition of example 12 in order to obtain the additive benefits of
improved reduction of cholesterol levels in patients (FF 1-6).
Appellant also contends that “by his own experimental findings and in
his own words, Orthoefer asserts that he has a surprising new form of
lecithin that is different than the powdered lecithin „old element‟ that is used
to start in the instant application” (Reply Br. 2).
We are not persuaded. As Appellant notes, Orthoefer teaches that the
“phospholipid- sterol preparation was extruded in an APV Baker model
MPF 50 extruder at a pressure of 850 psig and exited the die as a continuous,
smooth-feeling rope which was cut into dosage units” (Orthoefer 24, ll. 15-
20; FF 1). This is identical to a method used by the Specification in
formulation of tablets, where the Specification teaches that the “solid
material so prepared can then be compressed at elevated pressure and
extruded into a rope. The rope can be cut in segments to form tablets” (Spec.
10, ll. 9-11; FF 14). The method of tableting in the Specification is identical
to that disclosed by Orthoefer (FF 1, 2, 14).
Appellant contends that “there is no data that supports the proposition
that either proliposomes or liposomes are formed when this „new form‟ of
lecithin is exposed to water. And if it truly forms wax, it is unlikely” (Reply
Br. 3).
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We are not persuaded. There is specific evidence that supports the
finding that Orthoefer‟s preparation forms liposomes, which is the express
teaching by Orthoefer that “a solid phospholipid composition which may
contain active ingredients for oral ingestion in extruded tablet form, which
tablets are pro-liposomes that are converted into liposomes when they are
hydrated by water in the small intestine” (Orthoefer 10, ll. 9-12; FF 7). By
contrast, Appellant only provides attorney argument without any supporting
evidence whatsoever. See In re Pearson, 494 F.2d 1399, 1405 (CCPA 1974)
(“Attorney‟s argument in a brief cannot take the place of evidence.”).
Appellant then asserts that the data of Examples 14-16 in Orthoefer
“do not support the formation of proliposomes, which would be rapidly
converted into liposomes on exposure to the aqueous medium of the gut. In
fact, the data is most consistent with a wax-like structure in which a poorly
water soluble drug is slowly leeched out of the wax-like matrix” (Reply Br.
5).
We are not persuaded. First, Appellant has provided no evidence that
liposomes are not formed, but simply speculate to this effect based upon
release rates of drug, without any evidence of the stability of any liposomes
formed by these components or any other parameters. This also simply
represents attorney argument, and attorney argument which was not raised
until the Reply Brief, depriving us of the opinion of the Examiner. Second,
these arguments are based upon Examples 14-16, which are not the
examples upon which the Examiner relied. Thus, to the extent that these
examples yield different results than those of Examples 12 and 17, they are
not relevant to the prior art elements being relied upon to render the claimed
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invention obvious. Finally, if Appellant is suggesting that there is an
unexpected result, Appellant has provided no evidence that the results are
unexpected relative to the closest prior art of Orthoefer, which would be
Example 12, not Examples 14-16. In fact, Appellant provides no direct
comparison with the prior art. See In re Baxter Travenol Labs., 952 F.2d
388, 392 (Fed. Cir. 1991) (“[W]hen unexpected results are used as evidence
of nonobviousness, the results must be shown to be unexpected compared
with the closest prior art.”).
Appellant also discusses the micron size of “typical liposomes” (see
Reply Br. 6). We do not find this discussion persuasive because the issue is
not whether Orthoefer teaches “typical liposomes” but rather whether the
composition of Orthoefer, structurally identical to that claimed, inherently
forms liposomes which satisfy the 1 micron requirement. Consistent with
Best, Appellant provides no evidence that this composition fails to inherently
meet this requirement.
Conclusion of Law
The evidence of record supports the Examiner‟s conclusion that
Orthoefer renders claim 1 obvious.
SUMMARY
In summary, we affirm the rejection of claim 1 under 35 U.S.C. §
103(a) as obvious over Orthoefer. Pursuant to 37 C.F.R. § 41.37(c)(1), we
also affirm the rejection of claims 2-6, 8, 9, and 28-30 as these claims were
not argued separately.

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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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