Ex Parte Burton et al

Board of Patent Appeals and Interferences

Nov 8, 2010

10571437 (B.P.A.I. Nov. 8, 2010)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte MICHAEL DAVID BURTON, SR. and PAUL REUBEN KLINK
__________

Appeal 2010-007499
Application 10/571,437
Technology Center 1600
__________

Before DONALD E. ADAMS, MELANIE L. MCCOLLUM, and
JEFFREY N. FREDMAN, Administrative Patent Judges.

FREDMAN, Administrative Patent Judge.

DECISION ON APPEAL1
This is an appeal under 35 U.S.C. § 134 involving claims to
solubilized stabilized liquid formulations of ractopamine. The Examiner
rejected the claims as obvious. We have jurisdiction under 35 U.S.C. § 6(b).
We reverse.

1 The two-month time period for filing an appeal or commencing a
civil action, as recited in 37 C.F.R. § 1.304, or for filing a request
for rehearing, as recited in 37 C.F.R. § 41.52, begins to run from
the “MAIL DATE” (paper delivery mode) or the
“NOTIFICATION DATE” (electronic delivery mode) shown on
the PTOL-90A cover letter attached to this decision.
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Statement of the Case
“Ractopamine is a swine feed ingredient that directs nutrients to
improve production efficiencies and increase carcass lean gain” (Spec. 1).
The Specification teaches that the “invention relates to a solubilized
stabilized liquid formulation comprising from 5 to 30 % w/w of ractopamine
or a physiologically acceptable salt thereof; from 20 to 90% w/w of a liquid
nonionic cosolvent selected from polyethoxylated sorbitan fatty acid esters,
polyethoxylated vegetable oils, or both; and, from 5 to 75% w/w water”
(Spec. 3).
The Claims
Claims 14-20 are on appeal. Claim 14 and 20 are representative. The
remaining claims have not been argued separately and therefore stand or fall
together with claim 14. 37 C.F.R. § 41.37(c)(1)(vii). Claims 14 and 20 read
as follows:

14. A solubilized stabilized liquid formulation
comprising from 10 to 30% w/w of ractopamine or
a physiologically acceptable salt thereof; from 20
to 90% w/w of a liquid nonionic cosolvent selected
from polyethoxylated sorbitan fatty acid esters,
polyethoxylated vegetables oils, or both; and 5 to
75% w/w water.

20. The solubilized stabilized liquid formulation
of claim 19 wherein ractopamine or a
physiologically acceptable salt thereof is
ractopamine hydrochloride.

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The issues
A. The Examiner rejected claims 14-19 under 35 U.S.C. § 103(a) as
obvious over Metabolic2 and Gao3 (Ans. 4-5).
B. The Examiner rejected claim 20 under 35 U.S.C. § 103(a) as obvious
over Metabolic, Gao, and Watkins4 (Ans. 5-6).
C. The Examiner rejected claims 14-19 under 35 U.S.C. § 103(a) as
obvious over Mills5 and Gao (Ans. 6-7).
D. The Examiner rejected claim 20 under 35 U.S.C. § 103(a) as obvious
over Mills, Gao, and Watkins (Ans. 7-8).
A. and C. 35 U.S.C. § 103(a) over Metabolic and Gao or Mills and Gao
The Examiner finds that “Metabolic teaches formulations of
ractopamine (pg 3 lines 2-5) in solutions containing dispersing or wetting
agents which may include a condensation product of an alkylene oxide with
a fatty acid, for example, polyoxyethylene stearate” (Ans. 4). The Examiner
finds that “Mills et al discloses aqueous compositions which include
ractopamine . . . The actives may be mixed with commonly used diluents
and carriers, including sorbitan trioleate” (id. at 6).
The Examiner finds that “Gao et al teaches the use of various
surfactants to increase the solubility and stabilization, including

2 Belyea et al., WO 02/18436 A1, published Mar. 7, 2002, which
we will refer to as “Metabolic” for consistency with the Examiner
and Appellants.
3 Gao et al., US 6,231,887 B1, issued May 15, 2001.
4 Watkins et al., The effect of various levels of ractopamine
hydrochloride on the performance and carcass characteristics of
finishing swine, 68 J. ANIMAL SCIENCE 3588-3595 (1990).
5 Mills et al., GB 2,029,407 A, published Mar. 19, 1980.
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polyoxyethylene stearates, polyethoxylated vegetable oils (Cremophor EL)
and monolaurates (Polysorbate)” (Ans. 5).
The Examiner finds it obvious “when formulating the composition of
the primary reference, to select condensation products of an alkylene oxides
with a fatty acids, such as the surfactant/solvent compositions of the
secondary reference, given their disclosed ability to increase the solubility
and stabilize an insoluble active agent which has terminal hydroxyl groups”
(id.).
Appellants contend that the rejection improperly uses Gao “in which
certain portions of the reference are relied on while ignoring the teachings of
the reference as a whole” (App. Br. 5). Appellants contend that “the use of
Gao, either alone or in conjunction with the references relied on by the
Examiner, employs an impermissible hindsight analysis of the claimed
invention” (id.).
Appellants contend that
Gao lists the use of several solvents in column 5, lines 33-
42 which the Appellants attempted to use but found
unsuitable: propylene glycol (Example 1 - stability);
polyethylene glycol (Example 2 - stability ); glycerol (Table
4 - solubility); ethanol (Table 4 - solubility); triacetin (Table
4 - solubility); dimethyl isosorbide (Table 4 - solubility); and
dimethyl acetamide (Table 4 - solubility), for example.

(Id. at 7.) Appellants contend that the “assertion by the Examiner one could
simply pick and choose the correct solvent(s) based on Gao is not supported,
and in fact, the Appellants have demonstrated the solvents/surfactants listed
in Gao are not interchangeable with respect to the claimed invention” (id.).
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The issue with respect to this rejection is: Does the evidence of record
support the Examiner’s conclusion that either Metabolic and Gao or Mills
and Gao render obvious the claimed ractopamine stabilized liquid
formulation?
Findings of Fact
1. The Specification teaches that:
Example 3 consists of lists of liquid agents from
various chemical classes that have been investigated as
potential solvents or cosolvents for ractopamine. Not all of
the liquid agents in the lists below would be suitable for use
in livestock feed but serve as examples of liquid agents
which demonstrate one or more of 1) insufficient solvent
power to achieve a 10% solution of ractopamine; 2) result in
unacceptable degradation of ractopamine to afford related
substances; or 3) result in the formation of unacceptable
reaction product related substances.

(Spec. 12-13.)
2. The Specification teaches that solubility requires providing at
least “10% ractopamine HCl to liquid agent” in the solution (id. at 13).
3. The Specification defines “Stabilized” as “chemical stability
during storage as evaluated at, but not limited to, 25° C for at least 3 months
. . . where: 1) any new individual related substance does not exceed 0.2%
w/w of the concentration of ractopamine in an aqueous combination of
ractopamine or a physiologically acceptable salt thereof” (id. at 5).
4. Metabolic teaches that “the mammal may be a pig, and the beta
3 agonist may be either a selective or non-selective agonist to the beta 3
adrenergic receptor, such as ractopamine” (Metabolic 3, ll. 2-5).
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5. Metabolic teaches that “[a]queous suspensions normally
contain the active materials in admixture with excipients suitable for the
manufacture of aqueous suspension. Such excipients may be . . . a
condensation product of an alkylene oxide with a fatty acid, for example,
polyoxyethylene stearate” (Metabolic 9, l. 32 to 10, l. 4).
6. The Examiner finds that “Mills et al discloses aqueous
compositions which include ractopamine” (Ans. 6).
7. Mills teaches that a “phenethanolamine of the invention . . . can
be admixed with commonly used diluents and carriers, including . . .
sorbitan trioleate” (Mills 7, ll. 2-6).
8. Gao teaches:
non-ionic surfactants including Polyoxyl 40 hydrogenated
castor oil sold under the trade name, among the others,
Cremophor RH40; Polyoxyl 35 castor oil sold under the
trade name, among the others, Cremophor EL or Cremophor
EL; Polysorbates; Solutol HS-15; Tagat TO; Peglicol 6-
oleate; Polyoxyethylene stearates; Saturated Polyglycolyzed
Glycerides; or Poloxamers; all of which are commercially
available. The preferred surfactant is Cremophor RH140,
Cremophor EL or Polysorbate 80.
Saturated Polyglycolyzed Glycerides used herein
include Gelucire 44/14 or Gelucire 50/13.
Polyoxyethylene stearates used herein include Poloxyl
6 stearate, Poloxyl 8 stearate, Poloxyl 12 stearate and
Poloxyl 20 stearate.
Poloxamers used herein include Poloxamer 124,
Poloxamer 188, Poloxamer 237, Poloxamer 338 and
Poloxamer 407.
Polysorbates used herein include Polysorbate 20,
Polysorbate 40, Polysorbate 60 and Polysorbate 80.

(Gao, col. 5, ll. 43-63.)
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9. Gao teaches a composition which
comprises:
(a) a pyranone compound of formulas I, II, III or IV in an
amount of from about 1% to about 50% by weight of the
total composition,
(b) an amine in an amount of from about 0.1% to about 10%
by weight of the total composition,
(c) one or more pharmaceutically acceptable solvents in an
amount of from about 10% to about 30% by weight of the
total composition, and
(d) a pharmaceutically acceptable surfactant in an amount of
from about 10% to about 50% by weight of the total
composition.

(Gao, col. 6, ll. 20-33.)
Principles of Law
The Examiner has the initial burden of establishing a prima facie case
obviousness under 35 U.S.C. § 103. In re Oetiker, 977 F.2d 1443, 1445
(Fed. Cir. 1992).
Kubin stated that
[t]o differentiate between proper and improper applications
of “obvious to try,” this court outlined two classes of
situations where “obvious to try” is erroneously equated
with obviousness under § 103. In the first class of cases,
what would have been “obvious to try” would have been to
vary all parameters or try each of numerous possible choices
until one possibly arrived at a successful result, where the
prior art gave either no indication of which parameters were
critical or no direction as to which of many possible choices
is likely to be successful.

In re Kubin, 561 F.3d 1351, 1359 (Fed. Cir. 2009) (citing In re O’Farrell,
853 F.2d 894, 903 (Fed. Cir. 1988)).
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Analysis
The Examiner finds it obvious “when formulating the composition of
the primary reference, to select condensation products of an alkylene oxides
with a fatty acids, such as the surfactant/solvent compositions of the
secondary reference, given their disclosed ability to increase the solubility
and stabilize an insoluble active agent which has terminal hydroxyl groups”
(Ans. 5).
Appellants contend that
Gao lists the use of several solvents in column 5, lines 33-
42 which the Appellants attempted to use but found
unsuitable: propylene glycol (Example 1 - stability);
polyethylene glycol (Example 2 - stability ); glycerol (Table
4 - solubility); ethanol (Table 4 - solubility); triacetin (Table
4 - solubility); dimethyl isosorbide (Table 4 - solubility); and
dimethyl acetamide (Table 4 - solubility), for example.

(App. Br. 7.) Appellants contend that the “assertion by the Examiner one
could simply pick and choose the correct solvent(s) based on Gao is not
supported, and in fact, the Appellants have demonstrated the
solvents/surfactants listed in Gao are not interchangeable with respect to the
claimed invention” (id.).
We find that Appellants have the better position. Given the disclosure
in Appellants Specification that a very large number of solvents for
ractopamine either have unacceptable stability or insufficient solubility (FF
1, Spec. 12-18, Example 3), we do not find that this is the situation where
the selection of any solvent is merely a “predictable use of prior art elements
according to their established functions.” KSR Int’l Co. v. Teleflex Inc., 550
U.S. 398, 417 (2007). Rather, Appellants have shown extensive data in
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Example 3 which demonstrates significant unpredictability in identifying
solvents with acceptable stability and solubility. Even for the three solvents
in the Specification where ractopamine was shown to be soluble and stable,
solvent alone did not dissolve the ractopamine, and a solvent/water mixture
was required (see Spec. 19, Example 4).
We conclude that selection of solvents for ractopamine was not
predictable or simply the result of routine experimentation. Appellants’
Specification demonstrates that most of the solvents in Gao would not have
been expected to function (FF 1). In sum, there was no expectation that
selecting a solvent from Gao would predictably, or even likely, result in a
solvent which would dissolve ractopamine and remain stabilized (FF 1-3).
The instant situation fits O’Farrell’s first kind of error, since the prior art of
Metabolic, Mills, and Gao provide general guidance regarding ractopamine
and solvents (FF 2-7), but do not identify any specific guidance on
functional solvents for ractopamine.
Conclusion of Law
The evidence of record does not support the Examiner’s conclusion
that either Metabolic and Gao or Mills and Gao render obvious the claimed
ractopamine stabilized liquid formulation.
B. and D. 35 U.S.C. § 103(a) over Metabolic or Mills, Gao and Watkins
Having reversed the rejections over Metabolic, Mills, and Gao above,
from which claim 20 depends, we also reverse the obviousness rejections of
claim 20 for the reasons given above. The Examiner does not identify where
Watkins teaches predictable selection of the claimed solvents.
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SUMMARY
In summary, we reverse the rejection of claims 14-19 under 35 U.S.C.
§ 103(a) as obvious over Metabolic and Gao.
We reverse the rejection of claim 20 under 35 U.S.C. § 103(a) as
obvious over Metabolic, Gao, and Watkins.
We reverse the rejection of claims 14-19 under 35 U.S.C. § 103(a) as
obvious over Mills and Gao.
We reverse the rejection of claim 20 under 35 U.S.C. § 103(a) as
obvious over Mills, Gao, and Watkins.

REVERSED

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