Ex Parte Bell et al

Patent Trial and Appeal Board

Mar 15, 2017

12674727 (P.T.A.B. Mar. 15, 2017)

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.
12/674,727 04/18/2011 Gordon Bell 71657-US-REG-ORG-P 8898
85981 7590 03/15/2017
Syngenta Corp Protection, Inc.
410 Swing Road
Greensboro, NC 27409
EXAMINER
HIRT, ERIN E
ART UNIT PAPER NUMBER
1616
MAIL DATE DELIVERY MODE
03/15/2017 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 GORDON BELL,
CLAIR LOUISE HARRIS, and IAN DAVID TOVEY
Appeal 2016-002243
Application 12/674,727
Technology Center 1600
Before MELANIE L. McCOLLUM, JEFFREY N. FREDMAN, and
TIMOTHY G. MAJORS, Administrative Patent Judges.
FREDMAN, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal1 under 35 U.S.C. § 134 involving a composition
the form of an emulsion concentrate. The Examiner rejected the claims
obvious. We have jurisdiction under 35 U.S.C. § 6(b).
Statement of the Case
Background
Nowadays, the Formulation Chemist is required to address a
number of environmental criteria when developing new
formulations. Ideally, a suitable solvent will display many or
all of the following properties: an excellent dissolving power
for pesticides or other biologically active compounds; made
from plant or animal renewable resources; low skin irritation;
1 Appellants identify the Real Party in Interest as the Syngenta Crop
Protection, LLC (see App. Br. 3).
Appeal 2016-002243
Application 12/674,727
an ability to reduce the skin irritation associated with aggressive
formulation components, such as sodium lauryl sulphate; low
ecotoxicity, for example to daphnia; low volatile organic
content; and a high flash point. The compositions of the
present invention comprise a solvent which displays all or many
of these attractive properties.
(Spec. 1:16-24).
The Claims
Claims 1, 2, 4—18, and 20-23 are on appeal. Claim 1 is representative
and reads as follows:
1. A composition in the form of an Emulsion Concentrate
(EC) comprising a compound of formula I
CH3CH(0H)C(=0)NR1R2 (I)
where R1 and R2 are each CEE; and
at least one biologically active compound, which
comprises at least one aromatic five and/or six membered ring
wherein the ring contains at least one nitrogen as a ring
member,
with the proviso that the biologically active compound is
not cyproconazole.
The Issues
A. The Examiner rejected claims 1, 2, 4—18, and 20-23 under 35 U.S.C.
§ 103(a) as obvious over Zima,2 Sehring,3 Razzak,4 Ohsumi,5 and EPA6
(Final Act. 4—9).
2 Zima et al., DE 1 083 501, published June 15, 1960. We rely upon a
translation of Zima, added to the record herewith, with pages numbered 1—6
(“Zima Transl.”).
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Application 12/674,727
B. The Examiner provisionally rejected claims 1 and 2 on the ground of
nonstatutory provisional obviousness-type double patenting as being
unpatentable over claim 1 of copending US application 12/674,741 (Final
Act. 2-3).
A. 35 U.S.C. § 103(a) over Zima, Sehring, Razzak, Ohsumi, and EPA
The Examiner finds “Zima teaches a compound of formula I wherein
applicant's R1 and R2 are methyl. Zima also teaches wherein these
lactamide compounds are useful for solubilizing poorly water soluble, and
water insoluble drugs and agricultural chemicals (specifically fungicides,
insecticides, herbicides)” (Final Act. 5). The Examiner finds the “active can
comprise a 5 or 6 membered aromatic ring comprising nitrogen” (Id.).
The Examiner acknowledges that “Zima does not specifically teach
wherein the composition comprises additional solvents selected from those
listed in instant claim 5 or is used to form emulsion concentrates or contain
adjuvants such as emulsifiers” but finds “Sehring teaches lactamides of
formula I as solubilizers for poorly soluble agrochemical actives,
specifically triforine and Saprol” (Id.).
3 Sehring, R., DE 41 30 189 Al, published Mar. 18, 1993. We rely upon a
translation of Sehring, added to the record herewith, with pages numbered
1-12 (“Sehring Transl.”).
4 Razzak et al., US 2003/0180350 Al, published Sept. 25, 2003
(“Razzak”).
5 Ohsumi et al., US 4,837,242, issued June 6, 1989 (“Ohsumi”).
6 EPA Pesticide Fact Sheet, Isopyrazam, http://www.epa.gov/
pesticides/chem_search/reg^actions/pending/fs_PC-129222_05-
Oct-ll.pdf (Oct. 5 2011) (“EPA”).
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Application 12/674,727
The Examiner finds “Razzak teaches microemulsion pesticidal
compositions comprising poorly water soluble avermectins” and lactamides
“are useful as solubilizing agents for these lipophilic/hydrophobic
pesticides” (Final Act. 6). The Examiner finds “EPA fact sheet teaches that
isopyrazam is a poorly water soluble fungicide” and Ohsumi teaches
“pyrazole fungicides, a class of fungicides which would include isopyrazam,
are often formulated with organic solvents” (Id.).
The Examiner finds it obvious to “try dimethyl lactamide as taught by
Zima to solubilize isopyrazam, because these compounds were well known
in the art to be useful for solubilizing poorly water soluble/water insoluble
actives, and isopyrazam is known in the art to be a very poorly soluble
agrochemical active” (Final Act. 7).
The issue with respect to these rejections is: Does the evidence of
record support the Examiner’s conclusion that the prior art renders the
claims obvious?
Findings of Fact
1. The Specification teaches
a composition comprising a compound of formula I
CH3CH(0H)C(=0)NR! R2 (I)
where R1 and R2 are each independently hydrogen; or Ci-6 alkyl,
C2-6 alkenyl or C3-6 cycloalkyl, each of which is optionally
substituted by up to three substituents independently selected
from phenyl, hydroxy, C1-5 alkoxy, morpholinyl and NR3R4
where R3 and R4 are each independently C1-3 alkyl; or phenyl
optionally substituted by up to three substituents independently
selected from C1-3 alkyl; or R1 and R2 together with the nitrogen
atom to which they are attached form a morpholinyl,
pyrrolidinyl, piperidinyl or azepanyl ring, each of which is
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Application 12/674,727
optionally substituted by up to three substituents independently
selected from C1-3 alkyl.
(Spec. 1:32 to 2:10).
2. Zima teaches
using monosubstituted or disubstituted a-oxyacid amides of the
formula
(Ri = alkyl or phenyl, R2 and R3 mean methyl or ethyl, it also
being possible for R2 to be hydrogen), in particular lactic acid
diethyl amide as solubilizers for producing aqueous solutions of
medications poorly soluble or insoluble in water.
(Zima Transl. 2).
3. Zima teaches the “main area of application of the invention is
for medications. However, it can often be advantageous to put plant growth
promoters, insecticides, fungicides, and other pesticides into an aqueous
solution by the use of the solubilizers according to the invention” (Zima
Transl. 2).
4. Zima teaches “[s]olubilizers ... are used for producing aqueous
solutions of poorly soluble or insoluble active substances” (Zima Transl. 2).
Zima also teaches the “particular advantage of the new solubilizers consists
in their very low toxicity ... A further advantage consists in the fact that the
named oxyacid amides are very stable and produce neutrally reacting
aqueous solutions” (Zima Transl. 2—3).
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5. Zima teaches an example where “25 ccm of a 12% solution of
lactic acid diethyl amide dissolve 1.25 g of l-benzyl-3-ethyl-6,7-dimethoxy-
isoquinolinehydrochloride under weak heating” (Zima Transl. 3).
6. Sehring teaches
compounds with the general formula R-CO-NH-CH2-CH2OH,
in which R = methyl, ethyl, propyl, hydroxymethyl,
hydroxyethyl (CH3-CHOH or HO-CH2CH2-) which appear in
nearly all commercial plant protection agents that are used in
the form of emulsion concentrates, can be used as extremely
favorable solvents. This substance class replaces the sometimes
hazardous and toxic aliphatic and aromatic hydrocarbons still
used in enormous amounts and which are not safe for humans,
animals and the environment.
(Sehring Transl. 3). Sehring teaches “formulation of saprol (fungicide) with
lactic acid ethanolamide can be mentioned as an example of the superiority
of the emulsion concentrate” (Sehring Transl. 4).
7. Razzak teaches components that “are present in such
proportions such that they form microemulsions” (Razzak 124) where “the
lipophilic active is selected from the group including macrocyclic lactones,
including avermectins and milbemycins” (Razzak 119) and the “the organic
solvent is selected from the group including . . . N-(B-hydroxyethyl)
lactamide . . . and other pharmaceutically acceptable excipients” (Razzak
121).
8. Razzak teaches “[a]fter devising a base formulation we
conducted further experiments to determine what other factors affect the
uptake of water into the compositions” (Razzak 134) including “varying
amounts of sesame oil, ethyl oleate and medium chain mono- and di­
glycerides while maintaining the ratio of the surfactant and solvent, in this
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Application 12/674,727
case polysorbate 80 and benzyl alcohol in a ratio of 2:15 and 7:15
respectively” (Razzak 140).
9. Ohsumi teaches fungicides that include five membered rings
with nitrogen (see Ohsumi 1:20—50) that may be “formulated into
emulsifiable concentrates” with organic solvents (see Ohsumi 8:46—64) and
that “can be used as an active ingredient of fungicides to be used for paddy
field, plowland, orchard, pasture, turf and the like” (Ohsumi 9:25—27).
10. The Examiner finds the “EPA fact sheet teaches that
isopyrazam is a poorly water soluble fungicide, which is highly soluble in a
variety of organic solvents including aromatic solvents” (Ans. 6).
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.”
KSRInt’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 (Final Act. 4—9; FF 1—10) and agree that
the claims are rendered obvious by Zima, Sehring, Razzak, Ohsumi, and
EPA. Because we rely upon translations of Zima and Sehring that were not
previously of record (see, e.g., Ans. 7)7, we will designate our affirmance of
this rejection as a New Grounds of Rejection. We address Appellants’
arguments below.
7 See MPEP § 706.02 II (“If the document is in a language other than
English and the examiner seeks to rely on that document, a translation must
be obtained so that the record is clear as to the precise facts the examiner is
relying upon in support of the rejection.”)
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Application 12/674,727
Claim 1
Appellants contend “the teaching of Zima does not guide one skilled
in the art to (1) choose dimethyl lactamide from the teaching of Zima” (App.
Br. 13).
We do not find this argument persuasive. We note that Appellants’
own disclosed genus is significantly larger than the genus disclosed by Zima
(FF 1—2), subverting Appellants’ genus/species argument.
More significantly, Petering addressed a prior art reference in an
anticipation context that disclosed a small genus of chemical compounds,
finding:
A simple calculation will show that, excluding isomerism
within certain of the R groups, the limited class we find in
Karrer contains only 20 compounds. However, we wish to
point out that it is not the mere number of compounds in this
limited class which is significant here but, rather, the total
circumstances involved, including such factors as the limited
number of variations for R, only two alternatives for Y and Z,
no alternatives for the other ring positions, and a large
unchanging parent structural nucleus. With these circumstances
in mind, it is our opinion that Karrer has described to those with
ordinary skill in this art each of the various premutations here
involved as fully as if he had drawn each structural formula or
had written each name.
In re Petering, 301 F.2d 676, 681—682 (CCPA 1962). Here, in an
obviousness context, Zima’s structure contains only six alternatives based on
selection of R2 and R3 being either methyl or ethyl or for R2 hydrogen, and
with a very limited set of additional alternatives based on R1 being limited to
alkyl or phenyl substituents (FF 2). Just as in Petering, the limited number
of variations and the basic parental structure support the Examiner’s position
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Application 12/674,727
that the selection of dimethyl lactamide from this limited genus would have
been obvious, if not anticipated, by Zima.
We recognize that “lists and genera are often treated differently” but
“[t]his distinction collapses when the class of compounds that falls within
the genus is so limited that a person of ordinary skill in the art can “at once
envisage each member of this limited class.’” In re Gleave, 560 F.3d 1331,
1337—1338 (Fed. Cir. 2009) citing Eli Lilly & Co. v. Zenith Goldline
Pharms., Inc., 471 F.3d 1369, 1376 (Fed. Cir. 2006). Zima teaches such a
limited genus that dimethyl lactamide may be immediately envisaged, and
therefore would have been obvious to the person of ordinary skill in the art.
Appellants contend that “the phrase ‘A composition in the form of an
Emulsion Concentrate (EC)’ recited in independent claim 1 limits the
structure of the claimed invention, and consequently should be given
weight” (Reply Br. 3). Appellants further contend “the teaching of Zima
does not guide one skilled in the art to subsequently (1) seek out the
divergent teachings of (a) Sehring directed to an emulsion concentrate
comprising (i) a solvent other than dimethyl lactamide, namely, solvents
having Sehring’s formula” (App. Br. 14).
We agree with Appellants that the claims require the formulation in an
emulsion concentrate form. However, we are not persuaded that the prior art
does not render the claimed emulsion concentrate obvious. Zima teaches an
organic solvent useful in solubilizing active agents like insecticides,
fungicides and pesticides (FF 3) and both Sehring and Ohsumi suggest
dissolving such active agents into emulsion concentrates using organic
solvents (FF 6, 9). Razzak also teaches dissolving active agents into
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Application 12/674,727
emulsions with organic solvents (FF 7). The ordinary artisan would have
had reason to select Zima’s solvent not only as a known structural equivalent
(cf. Final Act. 8) but because a “particular advantage of the new solubilizers
consists in their very low toxicity ... A further advantage consists in the
fact that the named oxyacid amides are very stable and produce neutrally
reacting aqueous solutions” (FF 4).
Appellants contend that:
although the teaching of Zima mentions “fungicides,
insecticides and pesticides” as possible components in Zima’s
disclosed aqueous solutions, Zima does not suggest to one
skilled in the art (1) to incorporate “poorly water soluble/water
insoluble actives of any type,” into Zima’s disclosed aqueous
solutions, or (2) that Zima’s disclosed solubilizers are suitable
for use with “poorly water soluble/water insoluble actives of
any type”
(App. Br. 14).
We are not persuaded. Zima teaches “[s]olubilizers ... are used for
producing aqueous solutions of poorly soluble or insoluble active
substances” (FF 4) and teaches “it can often be advantageous to put plant
growth promoters, insecticides, fungicides, and other pesticides into an
aqueous solution by the use of the solubilizers according to the invention”
(FF 3). Thus, the ordinary artisan would have found it obvious to use
Zima’s solubilizers for prior art known poorly soluble insecticides,
fungicides, or pesticides in general, consistent with Wrigley, which found a
“strong case of obviousness based on the prior art references of record. [The
claim] recites a combination of elements that were all known in the prior art,
and all that was required to obtain that combination was to substitute one
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Application 12/674,727
well-known . . . agent for another.” Wm. Wrigley Jr. Co. v. Cadbury Adams
USA LLC, 683 F.3d 1356, 1364 (Fed. Cir. 2012). The same situation occurs
here, where all that is required is to solubilize known insecticides,
fungicides, or pesticides using Zima’s disclosed solubilizers (FF 2—10).
Appellants contend:
the teaching of Zima guides one skilled in the art to form
aqueous solutions, not emulsion concentrates. It is difficult for
Appellants to understand why one skilled in the art, given the
teaching of Zima directed to aqueous solutions comprising a
solubilizer having Zima’s formula and an active ingredient,
would have been guided and/or motivated to seek out the
teaching of Sehring, and subsequently choose to form an
emulsion concentrate instead of an aqueous solution as guided
within the teaching of Zima.
(App. Br. 14).
We do not find this argument persuasive because Sehring teaches
emulsion concentrates are a known delivery form for fungicides (FF 6) and
Razzak and Ohsumi teach emulsions formed with organic solvents for
solubilizing specific active compounds (FF 7, 9). Thus, the prior art in
combination suggests the use of both organic solvents and emulsions,
including emulsion concentrates, while Sehring teaches “the superiority of
the emulsion concentrate” (FF 6), a specific reason to select that delivery
form. The reason need not be found in the prior art, but may be implicit
when the improvement’ is technology-independent and the combination of
references results in a product or process that is more desirable” as in the
emulsion concentrate form suggested by Sehring in the instant case. See
DyStar Textilfarben GmbH & Co. Deutschland KG v. C.H. Patrick Co., 464
F.3d 1356, 1368 (Fed. Cir. 2006).
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Application 12/674,727
Appellants contend because “Sehring clearly guides one skilled in the
art, when forming an emulsion concentrate comprising a water-insoluble
fungicide (i.e., triforine), to utilize a solubilizer having Sehring’s formula”
that “the proposed combination of the teachings of Zima, Sehring, Razzak,
Oh sum i and the EPA Fact Sheet (even if deemed a proper combination of
teachings) actually teaches away from Appellants’ claimed composition”
(App. Br. 15).
We find the teaching away argument unpersuasive. A teaching away
requires a reference to actually criticize, discredit, or otherwise discourage
the claimed solution. See In re Fulton, 391 F.3d 1195, 1201 (Fed. Cir. 2004)
(“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”). Appellants do not persuasively identify any teaching in any of
the cited prior art that criticizes, discredits, or discourages the use of Zima’s
solubilizers.
Appellants contend “‘[o]ne cannot use hindsight reconstruction’” and
therefore “the proposed combination of the teaching of Zima with the
teaching of Sehring, the teaching of Razzak, the teaching of Ohsumi and the
EPA Fact Sheet is improper” (App. Br. 15).
We are not persuaded. While we are fully aware that hindsight bias
may plague determinations of obviousness, Graham v. John Deere Co., 383
U.S. 1, 36 (1966), we are also mindful that the Supreme Court has clearly
stated that the “combination of familiar elements according to known
methods is likely to be obvious when it does no more than yield predictable
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Application 12/674,727
results.” KSR, 550 U.S. at 416. In the instant case, selection of Zima’s
solubilizer for use in emulsion concentrate delivery of fungicides, pesticides,
or insecticides as taught by Sehring, using compounds taught by Razzak, and
Ohsumi would have reasonably been expected to yield the predictable result
of an effective fungicidal, pesticidal, or insecticidal composition (FF 2—10).
Appellants contend that:
Although the holding in the Takeda case involved
motivation for modifying a known compound, Appellants
respectfully submit that a similar analysis applies to the
required motivation for (1) selecting and combining possible
composition components from hundreds, thousands (or
hundreds of thousands) of possible composition components,
and (2) forming an emulsion concentrate with the selected
composition components.
(App. Br. 16—17).
We are not persuaded. Takeda involves the situation where none of
the species in the prior art genus fell within the scope of the claim, since
“[p]ioglitazone differs from compound b in two respects, and one would
have to both homologate the methyl group of compound b and move the
resulting ethyl group to the 5-position on the pyridyl ring in order to obtain
pioglitazone.” Takeda Chem. Indus., Ltd. v. Alphapharm Pty., Ltd, 492 F.3d
1350, 1360 (Fed. Cir. 2007).
In the instant case, every compound of Zima falls within the broad
scope of Appellants’ disclosure (FF 1), and the selection of R groups to
satisfy claim 1 is limited by the very small genus size of known equivalents
in Zima as already discussed. See Merck & Co., Inc. v. Biocraft Labs., Inc.,
874 F.2d 804, 807 (Fed. Cir. 1989) (“That the ‘813 patent discloses a
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Application 12/674,727
multitude of effective combinations does not render any particular
formulation less obvious.”)
Claim 15
Appellants contend that the combination
fails to teach or suggest an emulsion concentrate comprising,
inter alia, (i) a compound of formula 1; (ii) an agrochemical;
and (iii) a solvent, wherein the ratio of (i) compound of formula
1 to (ii) the agrochemical to (iii) the solvent is 1:1:1 or 2:1:1 or
2:1:2 or 3:1:1 or 3:1:2 or 4.5:1:4.5 or 6:1:3 as recited in
dependent claim 15.
(App. Br. 19).
We are not persuaded because Razzak evidences that optimization of
the ratio of components for active agent delivery in emulsions is routine (FF
8). Therefore, we agree with the Examiner that “it would have merely been
the optimization of amounts of lactamide to isopyrazam/agrochemical active
to carrier which were already taught in the prior art in order to develop the
composition of the instant claims” (Ans. 7). See In re Aller, 220 F.2d 454,
456 (CCPA 1955) (“[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.”)
Claims 16—18, and 23
Appellants contend the prior art “fails to teach or suggest an emulsion
concentrate comprising, inter alia, (i) dimethyl lactamide and (ii) 3-
difluoromethyl-1 -methyl-1 H-pyrazole-4-carboxylic acid(9-isopropyl-
l,2,3,4-tetrahydro-l,4-methano-naphthalen-5-yl)-amide as recited in
dependent claim 16” (App. Br. 20; cf. App. Br. 24).
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Application 12/674,727
We do not find this argument persuasive because, as discussed
already, Zima suggests solvents in a limited genus including dimethyl
lactamide (FF 2) for use with fungicides (FF 3) such as isopyrazam (the
compound name for the (ii) that was suggested by EPA) (FF 10). Appellants
provide no evidence of any secondary consideration for combining these
known components. As will be discussed next, the prior art teaches
treatment of plants with fungicidal emulsions (FF 6, 9).
Claims 21 and 22
We recognize, but find unpersuasive, Appellants’ contention that the
prior art
fails to teach or suggest a method of controlling an
agricultural pest comprising application to the pest, to
a locus comprising it or to a surface on which it is
capable of being present, of a pesticidally effective
amount of a composition according to claim 1 as
recited in dependent claim 21
(App. Br. 22). Sehring specifically teaches treatment of plants with
fungicides (FF 6) as does Ohsumi (FF 9). The ordinary artisan, after
forming an emulsion concentrate containing an insecticide, fungicide, or
pesticide, would have reasonably found it obvious to apply this composition
to surfaces hosting pests such as plants (FF 9).
Conclusion of Law
The evidence of record supports the Examiner’s conclusion that the
prior art renders the claims obvious.
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B. Obviousness-type double patenting
We summarily affirm the obviousness-type double patenting rejection
because Appellants do not address the rejection (see App. Br. 5, footnote 1).
See Manual of Patent Examining Procedure § 1205.02 (“If a ground of
rejection stated by the examiner is not addressed in the appellant’s brief, that
ground of rejection will be summarily sustained by the Board.”)
SUMMARY
We affirm the obviousness and provisional obviousness double­
patenting rejections, but designate our affirmance of the obviousness
rejection as a New Ground of Rejection because we relied upon translations
not previously of record.
This decision contains a new ground of rejection pursuant to 37
C.F.R. § 41.50(b). Section 41.50(b) provides “[a] new ground of rejection
pursuant to this paragraph shall not be considered final for judicial review.”
Section 41.50(b) also provides:
When the Board enters such a non-final decision, 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 prosecution
will be remanded to the examiner. The new ground of rejection
is binding upon the examiner unless an amendment or new
Evidence not previously of Record is made which, in the
opinion of the examiner, overcomes the new ground of rejection
designated in the decision. Should the examiner reject the
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Application 12/674,727
claims, appellant may again appeal to the Board pursuant to this
subpart.
(2) Request rehearing. Request that the proceeding be
reheard under § 41.52 by the Board upon the same Record. The
request for rehearing must address any new ground of rejection
and state with particularity the points believed to have been
misapprehended or overlooked in entering the new ground of
rejection and also state all other grounds upon which rehearing
is sought.
Further guidance on responding to a new ground of rejection can be
found in the Manual of Patent Examining Procedure § 1214.01.
AFFIRMED: 37 C.F.R, § 41.500?)
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Notice of References Cited
Application/Control No.
12/674,727
Applicant(s)/Patent Under
Reexamination
Examiner
Hirt
Art Unit
1616
Page 1 of 1
U.S. PATENT DOCUMENTS
* Document Number
Country Code-Number-Kind Code
Date
MM-YYYY Name CPC Classification US Classification
A us-
B us-
C US-
D US-
E US-
F US-
G US-
H US-
1 US-
J US-
K US-
L US-
M US-
FOREIGN PATENT DOCUMENTS
* Document Number
Country Code-Number-Kind Code
Date
MM-YYYY Country Name CPC Classification
N
O
P
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R
S
T
NON-PATENT DOCUMENTS
* Include as applicable: Author, Title Date, Publisher, Edition or Volume, Pertinent Pages)
U Translation of Zima et al., DE 1 083 501, published June 15, 1960.
V Translation of Sehring, R., DE 41 30 189 Al, published Mar. 18, 1993
w
X
*A copy of this reference is not being furnished with this Office action. (See MPEP § 707.05(a).)
Dates in MM-YYYY format are publication dates. Classifications may be US or foreign.
U.S. Patent and Trademark Office
PTO-892 (Rev. 01-2001) Notice of References Cited Part of Paper No.
PTO 118567 CC=DE DATE=19930318 KIND=A1
PN=4130189
NEW EMULSION CONCENTRATES FOR USE IN PLANT PROTECTION
[Neue Emulsionskonzentrate fur den Einsatz im Pflanzenschultz]
UNITED STATES PATENT AND TRADEMARK OFFICE
Washington, D.C. February 2017
Translated By: Phoenix Translations
100 N. Avenue B
Elgin, TX 78621
PUBLICATION COUNTRY
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(43) : 19930318
(45) :
(21) : P4130189.7
(22) : 19910911
(51) : A 01 N 25/02
A 01 N 37/26
// A0IN 25/30
(52) :
(33) :
(31) :
(32) :
(53) :
(56) :
(61) : P4112873.7
(72) : Inventor will be mentioned
later
(71) : Dr. Richard H. Sehring
1
TITLE
FOREIGN TITLE
(54) : New Emulsion Concentrates
for Use in Plant Protection
(54A) : Neue Emulsionskonzentrate
fur den Einsatz im
Pflanzenschultz
2
/I
Description
It was found that compounds with the general formula
R-CO-NH-CH2-CH2OH,
in which R = methyl, ethyl, propyl, hydroxymethyl, hydroxyethyl (CH3-
CHOH or HO-CH2CH2-)which appear in nearly all commercial plant
protection agents that are used in the form of emulsion concentrates,
can be used as extremely favorable solvents. This substance class
replaces the sometimes hazardous and toxic aliphatic and aromatic
hydrocarbons still used in enormous amounts and which are not safe
for humans, animals and the environment.
All the substances are very plant-compatible and in conjunction
with emulsifiers promote penetration of the active ingredients into
the plants and therefore produce a certain systemic effect and
therefore an improvement of effect. All compounds of this type are
readily biodegradable and produce no residues in the plants or in
soil.
The compounds are easily prepared from the methyl ester of the
formula
R-CO-OCH3 with ethanolamine
at elevated temperature.
3
The formulation of saprol (fungicide) with lactic acid
ethanolamide can be mentioned as an example of the superiority of the
emulsion concentrate.
The preparation of an emulsion concentration of saprol with
aliphatic or aromatic hydrocarbons has not been possible because of
the poor solubility. An emulsion concentrate can only be obtained
with the toxicologically critical dimethylformamide. It has now been
shown that when toxicologically safe lactic acid ethanolamide is
used, a very stable and highly effective emulsion concentrate is
obtained with simultaneous addition of surfactants, like
polyoxyethylene fatty acid esters, polyoxyethylene aliphatic alcohol
ethers, alkyl sulfonates and aryl sulfonates.
Claims
1. Use of ethanolamides of the general formula
R-CO-NH-CH2-CH2OH
R = methyl, ethyl, propyl, hydroxymethyl, hydroxyethyl (CH3-CHOH
or HO-CH2CH2-) as solvents for production of emulsion concentrates
that are used for general plant protection.
2. Lactic acid ethanolamide in combination with triforine and a
surfactant, like polyoxyethylene fatty acid esters, polyoxyethylene
aliphatic alcohol ethers, alkyl sulfonates and aryl sulfonates.
3. Fungicides, insecticides or herbicides consisting of 10-40%
of a given active ingredient, 50-80% of an ethanolamide of the above
4
formula (claim 1) as well as 3-20% of a surfactant according to
example 2.
5
PUBLICATION COUNTRY (19) : DE
DOCUMENT NUMBER (11) : 1083501
DOCUMENT KIND (12) : A
(13) :
PUBLICATION DATE (43) : 19600615
PUBLICATION DATE (45) :
APPLICATION NUMBER (21) :
APPLICATION DATE (22) : 19590326
INTERNATIONAL CLASSIFICATION (51) : A 61 k
IDENTIFICATION SYMBOL
DOMESTIC CLASSIFICATION (52) : 30 h 2/30
PRIORITY COUNTRY (33) :
PRIORITY NUMBER (31) :
PRIORITY DATE (32) :
UNIVERSAL DECIMAL CODE (53) :
LIST OF PRIOR ART DOCUMENTS (56) :
INVENTOR (72) : Dr . Otto Zima et al.
APPLICANT (71) : E. Merck AG, Darmstadt
TITLE (54) : Method for Production of
Solutions of Drugs Poorly
Soluble or Insoluble in
Water
6
FOREIGN TITLE (54A) : Verfahren zur Herstellung
von Losungen in Wasser
schwer- oder unloslicher
Arzneimittel
7
/I
A number of solubilizers that have a significant (sometimes
desired, but in many cases also interfering) physiological effect in
the employed amounts are used to produce aqueous solutions of active
ingredients, especially drugs that are poorly soluble or insoluble.
On the other hand, there is a lack of agents for this purpose that
have no effect in the employed amounts.
The present invention consists of using mono- or disubstituted
a-hydroxy acid amides of the formula
\,
(Ri = alkyl or phenyl, R2 = alkyl or phenyl, R2 and R3 denote methyl or
ethyl, in which R2 can also be hydrogen), especially lactic acid
diethylamide as a solubilizer to produce aqueous solutions of drugs
that are poorly soluble or insoluble in water. The mentioned
compounds are miscible with water in any ratio. Individually or mixed
with each other in aqueous solution, they have an excellent solution
capacity for active ingredients of any type that are poorly soluble
or insoluble in water. The main area of application of the invention
lies in drugs, but plant growth agents, insecticides, fungicides and
other pesticides can often be advantageously brought into aqueous
solution by using the solubilizers according to the invention.
The special advantage of the new solubilizers is their very low
toxicity so that the harmful or even interfering side effects that
cannot be ruled out during use of many known solubilizers are
avoided. The substances according to the invention do not have an
intrinsic pharmacological effect; thus, 1 g of substance per kilogram
of body weight injected intravenously in mice is tolerated without
symptoms. Another advantage is that the mentioned hydroxy acid amides
are readily storable and produce neutral reacting aqueous solutions.
The pH value of the solution generally lies between 6 and 7.
Examples
1. 150 mg A1-dehydrocortisone is dissolved under heating in
25 cm3 of a 30% aqueous lactic acid diethylamide solution containing
10% alcohol. No crystals precipitate from the sterilized solution on
cooling.
2. 100 mg A1-dehydrocortisone is dissolved under heating in
10 cm3 of a 50% solution of lactic acid diethylamide.
/ 2
3. 25 cm3 of a 12% solution of lactic acid diethylamide dissolves
under weak heating 1.25 g l-benzyl-3-ethyl-6,7-dimethoxyisoquinoline
hydrochloride.
4. 2.5 g l-benzyl-3-ethyl-6,7-dimethoxyisoquinoline and 1 g
nicotinic acid are dissolved in 50 cm3 of an aqueous solution of
lactic acid diethylamide.
9
5. 10 cm3 of a 30% solution of lactic acid diethylamide dissolves
100 mg of strophanthin under slight heating.
6. 4 g glycolic acid diethylamide in 10 cm3 water easily
dissolves 200 mg theophylline.
7. 3 g glycolic acid diethylamide, 50 mg A1-dehydrocortisone and
1 cm3 alcohol in 10 cm3 of water produce a stable clear solution.
8. 6 g mandelic acid ethyl amide in 25 cm3 water produces a
storable solution with 6 g dimethylaminophenyldimethylpyrazolone.
9. 100 mg theophylline is smoothly dissolved in a solution of
1 g mandelic acid ethyl amide in 10 cm3 water.
10. 10 g ajmalicine ethanesulfonate, 150 g lactic acid
diethylamide, 100 cm3 alcohol and 50 cm3 IN acetic acid produce a
clear storable solution made up to 1000 cm3 with water.
11. 5 g ethylcyclohexenylbarbituric acid is dissolved in 25 g
lactic acid diethylamide and 10 g alcohol and made up to 100 cm3 with
water.
12. 0.5 g phenylethylbarbituric acid produces a storable
solution with 2.5 g lactic acid diethylamide, 1 g alcohol and 6 cm3
water.
Comparative examples were produced with the a-hydroxy acid
amides
/ 3
10
according to the invention and some known readily effective and
chemically comparable solubilizers are shown in the following table.
Dimethylaminophenyldimethylpyrazolone, theophylline and
/ 4
A1-dehydrocortisone were used as poorly soluble drugs. Ethylurethane,
ethylenediamine, triethanolamine and methylacetamide were used as
comparable solubilizers.
Ethyl­
urethane
Ethylene­
diamine
Triethan­
olamine
Methyl­
acetamide
Solubilizer
according to
the invention
Example
Dimethylaminophenyldimethylpyrazolone . . 6 g 800 mg 1.4 g 3 . 9 g 6 g 8
Theophylline ...................................................................... 190 mg 2 0 0 mg 2 0 0 mg 15 0 mg 2 0 0 mg 6
A1-Dehydrocortisone ................................................... 14 0 mg 145 mg 15 0 mg 60 mg 15 0 mg 1
A1-Dehydrocortisone ................................................... 95 mg 100 mg 90 mg 2 8 mg 100 mg 2
/ 3
The table shows how many grams or milligrams of the drug
mentioned on the left can be brought into aqueous solution under
otherwise identical conditions, using the known solubilizers listed
above and the solubilizers according to the invention. From the
figures in the table it is apparent that the a-hydroxy acid amides
according to the invention generally have a better, or at least the
same, solubilizing capacity as the known solubilizers. The
solubilizers according to the present invention do not have an
intrinsic pharmacological effect; their use is therefore also
advantageous if their solubilizing effect is only just as high as the
aforementioned known solubilizers, which have an intrinsic (in many
cases undesired) pharmacological effect.
11
/ 4
CLAIMS:
1. Method for production of solutions of drugs poorly soluble or
insoluble in water, characterized by the fact that a-hydroxy acid
amides of the formula
, id
Rt...CKOH....CO....K
(Ri = alkyl or phenyl, R2 = alkyl or phenyl, R2 and R3 denote
methyl or ethyl, in which R2 can also be hydrogen) are used as
solubilizer.
2. Method according to claim 1, characterized by the use of
lactic acid diethylamide as solubilizer.
12
PTO 118495 CC=DE DATE=19600615 KIND=B
PN=1083501
METHOD FOR PRODUCING SOLUTIONS OF MEDICATIONS POORLY SOLUBLE
OR INSOLUBLE IN WATER
[VERFAHREN ZUR HERSTELLUNG VON LOSUNGEN IN WASSER SCHWER-
ODER UNLOSLICHER ARZNEIMITTEL]
Otto Zima, et al.
UNITED STATES PATENT AND TRADEMARK OFFICE
Washington, D.C. February 2017
Translated by: FLS, Inc.
PUBLICATION COUNTRY
DOCUMENT NUMBER
DOCUMENT KIND
PUBLICATION DATE IN BULLETIN
INTERNATIONAL CLASSIFICATION
APPLICATION NUMBER
APPLICATION DATE
PRIORITY NUMBER
PRIORITY DATE
PRIORITY COUNTRY
APPLICANT
INVENTORS
TITLE
(19
(11
(12
(46
(51
(21
(22
(31
(32
(33
(71
(72
(54
DE
1083501
B
19600615
A61K 47/18
DEI 95 9M04 0 970
19590326
DEI 95 9M04 0 970
19590326
DE
E. MERCK AG
ZIMA, OTTO; SCHORRE, GUSTAV
METHOD FOR PRODUCING SOLUTIONS
OF MEDICATIONS POORLY SOLUBLE OR
INSOLUBLE IN WATER
FOREIGN TITLE [54A] : VERFAHREN ZUR HERSTELLUNG VON
LOSUNGEN IN WASSER SCHWER- ODER
UNLOSLICHER ARZNEIMITTEL
1
Description /I
Solubilizers that produce a distinct - often desirable, but in
many cases disturbing - physiological effect, are used for producing
aqueous solutions of poorly soluble or insoluble active substances, in
particular medications. However, there is a lack of agents that are
practically without effect, i.e. in the amounts used, for this
purpose. The present invention consists in using monosubstituted or
disubstituted a-oxyacid amides of the formula
Jt
iq — 0 H 0 H—G 0 “ N'
'll,
(Ri = alkyl or phenyl, R2 and R3 mean methyl or ethyl, it also being
possible for R2 to be hydrogen), in particular lactic acid diethyl
amide as solubilizers for producing aqueous solutions of medications
poorly soluble or insoluble in water. The named compounds are miscible
with water in any ratio. They possess an outstanding dissolving
capacity for substances of any kind that are poorly soluble or
insoluble in water, individually or in a mixture. The main area of
application of the invention is for medications. However, it can often
be advantageous to put plant growth promoters, insecticides,
fungicides, and other pesticides into an aqueous solution by the use
of the solubilizers according to the invention.
The particular advantage of the new solubilizers consists in
their very low toxicity, with which the harmful or quite disturbing
* Numbers in the margin indicate pagination in the foreign text.
2
side-effects that cannot be eliminated in case of using many known
solubilizers, are avoided. The substances according to the invention
do not possess any pharmacological effect; thus in the case of mice
e.g. 1 g of substance per kilogram of body weight, injected
intravenously, is tolerated without symptoms. A further advantage
consists in the fact that the named oxyacid amides are very stable and
produce neutrally reacting aqueous solutions.
The pH value of the solutions for the most part is between 6 and
7.
Examples
1. 150 mg of Zh-dehydrocortisone are dissolved under heating in
25 ccm of a 30% aqueous lactic acid diethyl amide solution, which
contains 10% alcohol. No crystals precipitate from the sterilized
solution upon cooling.
2. 100 mg of Zh-dehydrocortisone are dissolved under heating in
10 ccm of a 50% solution of lactic acid diethyl amide.
3. 25 ccm of a 12% solution of lactic acid diethyl amide
dissolve 1.25 g of l-benzyl-3-ethyl-6,7-dimethoxy-isoquinoline-
hydrochloride under weak heating.
4. 2.5 g of l-benzyl-3-ethyl-6,7-dimethoxy-isoquinoline and 1 g
of nicotinic acid are dissolved in 50 ccm of an aqueous solution of
lactic acid diethyl amide.
5. 10 ccm of a 30% solution of lactic acid dimethyl amide
dissolve 100 mg of strophantine under slight heating.
3
6. 4 g of glycolic acid diethyl amide in 10 ccm of water
smoothly dissolve 200 mg of theophylline.
7. 3 g of glycolic acid diethyl amide, 50 mg of h1-
dehydrocortisone and 1 ccm of alcohol in 10 ccm of water give a
constant clear solution.
8. 6 g of mandelic acid ethyl amide in 25 ccm of water with 6 g
of dimethyl aminophenyl dimethyl pyrazolone gives a stable solution.
9. 100 g of theophylline dissolve smoothly in a solution of 1 g
of mandelic acid ethyl amide in 10 ccm of water.
10. 10 g of ajmalicine ethane sulfonate, 150 g of lactic acid
diethyl amide, 100 ccm of alcohol, and 50 ccm 1-n acetic acid, filled
with water to 1000 ccm, give a clear stable solution.
11. 5 g of ethyl-cyclohexenyl-barbituric acid are dissolved in
25 g of lactic acid diethyl amide and 10 g of alcohol and filled with
water to 100 ccm.
12. 0.5 g of phenyl-ethyl-berbituric acid with 2.5 g of lactic
acid diethyl amide, 1 g of alcohol, and 6 ccm of water give a stable
solution.
The following table presents comparison experiments, which were
conducted with the a-oxyacid amides according to the invention and
Some known, very effective, and chemically more or less comparable [2_
solubilizers.
Dimethyl aminophenyl dimethyl pyrazolones, theophylline, and h1-
dehydrocortisone were used as the poorly soluble medications. Ethyl
4
urethane, ethylene diamine, triethanol amine, and methyl acetamide
were used as comparable solubilizers.
Ethyl-
urethane
Ethyl­
ene
diamine
Trietha­
nol amine
Methyl
acetam­
ide
Solubili­
zer
according
to the
invention
Example
Dimethyl aminophenyl dimethyl
Pyrazolone....................................... 6 g 800 mg 1.4g 3.9 g 6g 8
Theophylline............................................. 190 mg 200 mg 200 mg 150 mg 200 mg 6
ZT-dehydrocortisone.......................... 140 mg 145 mg 150 mg 60 mg 150 mg 1
ZT-dehydrocortisone.......................... 95 mg 100 mg 90 mg 2 8 mg 100 mg 2
The table shows how many grams or milligrams one of the known
medications indicated on the left can be put into an aqueous solution
under the most equal possible other conditions with the use of the
known solubilizers presented above as well as the solubilizers
according to the invention. The numbers in the table show that the a-
oxyacid amides according to the invention for the most part have a
solubilizing effect that is better than, or at least the same as, the
known solubilizers. The solubilizers according to the present
invention do have no particular pharmacological effect; therefore
their use is also advantageous when their solubilizing effect is only
as great as that of the above-mentioned known solubilizers, which
have a particular - in many case undesirable - pharmacological
effect.
5
PATENT CLAIMS
1. A method for producing solutions of medications poorly
soluble or insoluble in water, wherein a-oxyacid amides of the
formula
sv--choh--co..~n;
XR,
(Ri = alkyl or phenyl, R2 and R3 mean methyl or ethyl, it also being
possible for R2 to be hydrogen) are used as solubilizers.
2. The method according to Claim 1, characterized by the use of
lactic acid diethyl amide as solubilizer.
6