GUERBET

Patent Trials and Appeals Board

Sep 28, 2020

14762064 - (D) (P.T.A.B. Sep. 28, 2020)

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.
14/762,064 07/20/2015 Caroline Robic 51585-146888 3162
21888 7590 09/28/2020
THOMPSON COBURN LLP
ONE US BANK PLAZA
SUITE 3500
ST LOUIS, MO 63101
EXAMINER
SCHLIENTZ, LEAH H
ART UNIT PAPER NUMBER
1618
NOTIFICATION DATE DELIVERY MODE
09/28/2020 ELECTRONIC
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.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
following e-mail address(es):
IPDOCKET@THOMPSONCOBURN.COM
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
_________________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
_________________

Ex parte CAROLINE ROBIC and MARC PORT

_________________

Appeal 2020-000689
Application 14/762,064
Technology Center 1600
_________________

Before RICHARD M. LEBOVITZ, JASON V. MORGAN, and
DEBORAH KATZ, Administrative Patent Judges.

KATZ, Administrative Patent Judge.

DECISION ON APPEAL

Appellant1 seeks our review,2 under 35 U.S.C. § 134(a), of the
Examiner’s decision to reject claims 1–19. We have jurisdiction under 35
U.S.C. § 6(b). We AFFIRM.

1 We use the word “Appellant” as defined in 37 C.F.R. § 1.42. Appellant
identifies the real party-in-interest as Guerbet. (Appeal Br. 4.)
2 We consider the Non-Final Office Action issued October 26, 2017 (“Non-
Final Act.”), the Final Office Action issued July 13, 2018 (“Final Act.”), the
Appeal Brief filed April 26, 2019 (“Appeal Br.”), and the Examiner’s
Answer issued on August 1, 2019 (“Ans.”).
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The Examiner rejected claims 1–19 under 35 U.S.C. § 103(a) as being
obvious over Jarzyna3 and Port.4 (See Final Act. 2–6.) Appellant argues the
merits of the patentability of the claims as a group, focusing on claim 1.
(See Appeal Br. 7.) Accordingly, we focus on claim 1 in our analysis.
Appellant’s Specification is directed to magnetic nanoemulsions that
are used as contrast agents in magnetic resonance imaging (“MRI”). (Spec.
1:3–4.)
Appellant’s claim 1, with additional indentations to clarify claim
elements, recites:
An oil-in-water nanoemulsion composition, comprising:
50 to 90% by weight of aqueous phase;
9.5 to 49.5% by weight of lipid phase nanodroplets,
wherein the lipid phase nanodroplets comprise an oil and
magnetic particles,
wherein the oil comprises at least 70% by weight of C6-
C18 saturated fatty acid glycerides, and
wherein the magnetic particles comprise an iron
compound and are covered with one or more C8-
C22 fatty acids; and
0.38 to 4.95% by weight of a mixture of surfactants at the
interface between the aqueous and lipid phases,
wherein the mixture of surfactants comprises at least one
amphiphilic lipid and at least one amphiphilic
targeting ligand, and
wherein the mixture of surfactants is 4 to 10% by weight
of the oil;

3 Jarzyna et al., Iron oxide core oil-in-water emulsions as a multifunctional
nanoparticle platform for tumor targeting and imaging, 30 BIOMATERIALS
6947–54 (2009).
4 Port et al., International Patent Application Publication WO 2012/084981
A1, published June 28, 2012), cited to as U.S. Patent 9,770,520 B2, issued
Sept. 26, 2017.
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wherein the composition comprises more than 100 mmol of
iron per liter of composition.

(Appeal Br. 21.)
The Examiner finds that Jarzyna teaches iron oxide oil-in-water
emulsions that are multifunctional nanoparticles useful for imaging. (See
Non-Final Act. 3.) The Examiner finds further that the oil-in-water
emulsions of Jarzyna are composed of a hydrophobic oil core component,
including nanocrystals of iron oxides, and that the oil droplets are stabilized
by a lipid mixture of DSPC and PEG-DSPE to favor formation of small
particles in a size range of 30–100 nm. (See Non-Final Act. 3, citing Jarzyna
6947–48 and Fig. 1A.) Figure 1A of Jarzyna is reproduced below.

Figure 1A depicts a schematic diagram of different sized nanoemulsions
including soybean oil, oleic acid coated iron oxide nanoparticles, and the
lipids DSPC and PEG-DSPE. (See Jarzyna 6948.) Cy5.5, a near infrared
fluorophore, is incorporated into the nanoemulsion for optical imaging. (See
id.)
Jarzyna teaches several different compositions for the synthesis of
nanoemulsions. (See Jarzyna 6949.) But, as the Examiner finds, Jarzyna
does not teach an emulsion composition comprising a lipid phase of oil that
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is 70% by weight of C6–18 saturated fatty acid glycerides and does not teach
an amphiphilic targeting ligand. (See Non-Final Act. 4.)
Port teaches an oil-in-water nanoemulsion composition for MRI
comprising an aqueous phase that is 70% to 90% by weight of the
composition, a lipid phase comprising an oil, which is 9.5% to 29.5% by
weight of the composition, and a surfactant at the interface between the
aqueous and lipid phases. (See Port Abstract and 4:30–53.) Port teaches
further that the surfactant of the oil-in-water emulsion comprises at least one
amphiphilic paramagnetic metal chelate and optionally an amphiphilic lipid,
with the total content of surfactant being between 4% and 10% by weight
relative to the oil and between 0.35% and 2.95% by weight relative to the
composition. (See id.) The oil of the nanoemulsion composition of Port can
comprise at least 70% of saturated C6–C18. (See id.)
Port teaches, further, that nanoemulsions can include, in the surfactant
layer, one or more targeting biovectors or ligands that specifically recognize
a receptor or enzyme. (See Port 3:53–63.) Port teaches that amphiphilic
biovectors are 0.01% to 10% by weight of the total amount of surfactants.
(See Port 5:41–43.) Port teaches “selecting optimized compositions
comprising sufficient surfactant to stabilize the size of the nanoparticles, but
not too much so as to avoid insufficient incorporation of the biovectors.”
(Port 4:15–18.)
The Examiner finds that it would have been obvious to one of
ordinary skill in the art at the time of the invention to substitute an oil
comprising at least 70% by weight of C6–C18 saturated fatty acid glyceride
for the soybean oil in the nanoemulsions taught by Jarzyna because Port
teaches that compositions using polyunsaturated oils pose several technical
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problems, including long term stability problems due to oxidation. (See
(Non-Final Act. 6–7, citing Port 2:47–58.) The Examiner also finds that it
would have been obvious to include an amphiphilic targeting ligand because
amphiphilic biovectors allow for access to physiological zones such as the
blood brain barrier in order to locate a pathological area. (Non-Final Act. 6–
7, citing Port 5:53–62 and 5:25–28.)
The Examiner finds further that it would have been obvious to arrive
at the claimed concentrations of the aqueous phase, oil, surfactant, and iron
by routine optimization because these concentrations are result-effective
variables. (See Non-Final Act. 7–8.) Specifically, the Examiner finds that
the prior art shows that relaxation rates of a paramagnetic metal ion are a
function of the metal concentration, indicating to one of ordinary skill in the
art that metal concentration is a result-effective variable, which may be
optimized to determine the most favorable concentration for imaging. (See
Final Act. 4, citing Port 69:1–16.)
Appellant argues that a skilled artisan would not have been motivated
to modify the nanoemulsion of Jarzyna to include an amphiphilic targeting
ligand as taught in Port because doing so would interfere with the intended
purpose of Port. (See Appeal Br. 11–12.) According to Appellant,
fluorescent agents as taught in Jarzyna prevent the inclusion of vectorising
agents, such as amphiphilic targeting ligands. (See id.) Appellant cites to
the discussion of Jarzyna in the Specification in support of this argument.
(See Appeal Br. 11, n.19.) Specifically, the Specification states:
In Jarzyna et al (Biomaterials, 30, 6947-6954, 2009) are
described iron nanoparticle emulsions notably consisting of
magnetite (Fe3O4) covered with oleic acid, the oily phase of
these emulsions being mainly made from soya bean oil (in this
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case a polyunsaturated oil. These nanoemulsions are coupled
with a fluorophore Cy5.5, a fluorescent agent belonging to
cyanines. This type of compound does not give the possibility of
vectorising a nanosystem. This just gives the possibility of being
able to ascertain that what is seen in imaging is visible in
fluorescence. The described nanoemulsions have a reduced iron
loading capacity (not more than 15 mmol of iron per liter of
emulsion) and therefore do not give the possibility of obtaining
MRI images of sufficient quality.

(Spec. 3:15–23.) We do not read this portion of Appellant’s Specification to
indicate that the fluorescent agent of Jarzyna would interfere with an
amphiphilic targeting agent. Rather, this disclosure indicates that Jarzyna’s
agent does not by itself provide for amphiphilic targeting. Appellant does
not point to any explanation, either in the Specification or elsewhere, that
supports an interpretation of this portion as meaning that a fluorescent agent
would interfere with an amphiphilic targeting agent. Appellant does not
direct us to any evidence to explain why both could not exist in the same
nanoemulsion. Accordingly, this argument does not persuade us that the
Examiner erred.
Appellant also argues that a skilled artisan would not have been
motivated to replace the soybean oil of Jarzyna with the oil used in Port.
(See Appeal Br. 12–15.) First, Appellant argues that the iron oxide
nanocrystal nanoemulsions of Jarzyna are “entirely distinct” from the metal
chelate nanoemulsions of Port. (See id. at 12–13.) In support, Appellant
points to the statement in Port that the “nanoemulsion does not comprise any
metallic nanocrystals.” (See id. citing Port 4:58–59.) Appellant does not
explain this statement in Port any further. Thus, it is not clear if metallic
nanocrystals are excluded for technical reasons or for other reasons. It is
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also not clear how this statement establishes that metallic nanocrystals
nanoemulsions are “entirely distinct” from metal chelate nanoemulsions.
Second, Appellant argues that the Examiner is incorrect in finding that
a skilled artisan would have been motivated to replace the soybean oil of
Jarzyna with the oil of Port. (See Appeal Br. 13–14, citing Non-Final Act 6–
7.) Appellant argues that the soybean oil emulsion of Jarzyna is injectable
and, thus, compatible with crossing biological barriers of organs without
toxic effects. (See Appeal Br. 13, citing Jarzyna sections 2.8, 3.3, and 3.4.)
This argument is not persuasive because it does not address the teaching in
Port that unsaturated oils, such as the type of soybean oil used in Jarzyna,
are sensitive to oxidation resulting “firstly in a problem of stability of the
emulsion over time, especially for storage for several months (typically 3
years for injectable contrast agents), and secondly in a risk (associated with
the presence of oxygen) of impairment of the paramagnetic behavior of the
product for medical imaging MRI examinations.” (Port 2:52–58.) Thus, the
evidence supports the Examiner’s determination that one of ordinary skill in
would have had reason to have substituted the soybean oil in Jarzyna with
the oil of Port.
Appellant’s argument that the statement in Port does not apply to the
nanoemulsions of Jarzyna because they are taught to be stable for at least
three months, is similarly unpersuasive because Port addresses longer term
stability “typically 3 years.” (See Appeal Br. 13.) Appellant’s argument that
the concern about oxidation taught in Port is irrelevant to the metallic oxide
nanoparticles of Jarzyna, is also unpersuasive because Port specifically
addresses the unsaturated oils, not the metallic portion of the nanoparticles.
(See Appeal Br. 14.)
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Appellant argues further that the teachings in Port regarding problems
of polyunsaturated oils were made with respect to lanthanide chelate
emulsions disclosed by U.S. Patent Application Publication 2007/0148194
(“Amiji”), not with respect to soybean oil in metallic oxide nanocrystal
emulsions. (See Appeal Br. 14–15.) We are not persuaded by this argument
because regardless of the disclosure of Amiji, Port states that “unsaturated
oils are sensitive to oxidation” resulting in stability problems and
impairment in MRI examinations and soybean in one such oil. (Port 2:52–
58.)
Appellant’s arguments fail to persuade us that the problem of long
term stability due to oxidation of nanoemulsions made with unsaturated oils
is not a reason expressly taught in Port that would motivate one of ordinary
skill to look for a substitution. In light of this express teaching, we are not
persuaded that the Examiner resorted to hindsight reasoning to find a
motivation, as Appellant argues. (See Appeal Br. 15.)
Appellant argues that the Examiner erred because the combined
teachings of Jarzyna and Port do not teach or suggest an oil-in-water
nanoemulsion with more than 100 mmol iron per liter because they do not
encompass or overlap the claimed concentration. (See Appeal Br. 15–19.)
Appellant argues that although Port may teach that relaxation rate is a
function of gadolinium concentration in metal chelate emulsions, Jarzyna
teaches that the relaxation rate (relaxivity) is dependent upon the size of the
nanoparticles. (See Appeal Br. 16, citing Jarzyna 6950 (“Interestingly, we
observed r1 and r2 to be size dependent . . .”), Fig. 1.) According to
Appellant, this renders the finding that metal concentration is a result-
effective variable irrelevant to metal particle nanoemulsions. (See id.) We
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are not persuaded by Appellant’s argument because, while particle size may
be one result-effective variable, this does not mean that additional variables
would be excluded from affecting the efficacy of the emulsion in imaging.
Furthermore, Jarzyna teaches that iron content affects relaxation rate,
wherein “[t]he high payload potential of the nanoemulsions allowed us to
load high quantities of iron oxide nanocrystals, causing an remarkably high
transverse relaxivity (r2), which is desirable forT2(*)-weighted MRI.”
(Jarzyna 6953; see Ans. 7.) Thus, Jarzyna teaches that high quantities of
iron oxide nanocrystals are desirable.
Appellant argues further that the Examiner erred in determining that
an ordinarily skilled artisan would achieve the claimed metal concentration
of 100 mmol of iron per liter of composition by routine optimization because
the “general conditions” of claim 1 are not disclosed in Jarzyna or Port. (See
Appeal Br. 16–18.) According to Appellant, Jarzyna teaches a composition
with a maximum of 15 mmol of iron per liter and Port teaches a composition
of only 0.1 to 2.5 mmol of gadolinium and that the “extremely large
difference” between the claimed concentration and the range taught in
Jarzyna cannot support a finding of obviousness. (Appeal Br. 17.)
Appellant argues further that because the concentration taught in Jarzyna
would have been too low to obtain quality MRI images, the Jarzyna
composition was not vectorized, and the Port disclosure is directed to a
metal chelate nanoemulsion, the Examiner’s determination that the iron
concentration is a result-effective variable suitable for optimization through
routine experimentation is a reversible error. (See Appeal Br. 18.)
We are not persuaded by Appellant’s arguments. The cited prior art
indicates that it was known in the art that increased iron concentrations
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allow increased relaxivity in emulsions for MRI.5 (See Jarzyna 6953; Port
69:1–4.) Because Port teaches an oil-in-water emulsion with many of the
same conditions recited in claim 1 (an aqueous phase, a lipid phase with C6–
C18 saturated fatty acids, and surfactants at the interface between the
aqueous and lipid phases comprising at least one amphiphilic paramagnetic
metal chelate) we are not persuaded that the Examiner improperly relied on
In re Aller, 220 F.2d 454, 456 (CCPA 1955), to find that “where the general
conditions of a claim are disclosed in the prior art, it is not inventive to
discover the optimum or workable range by routine experimentation.”6
Appellant argues further that even if the iron concentration is a result-
effective variable that could be determined by routine optimization, the
claimed iron concentration, increasing the iron concentration nearly seven
times to yield a vectorized nanoparticle emulsion with enough iron to
produce “very great quality” MRI is a different in new and unexpected result

5 We note that Appellant’s Specification refers to a 2009 publication, which
the Specification states “the nanoemulsions described in this document also
have a reduced iron loading capacity (not more than 80 mmol of iron per
liter of emulsion) and therefore do not give the possibility of obtaining an
optimum sensitivity in MRI.” (See Spec. 3:25, citing “Senpan et al (JACS,
Vol. 3, No. 12, 3917–3926, 2009” (the correct citation appears to be
“Senpan et al., ACS Nano. 3(12):3917–3926 (2009)”).)
6 Appellant also cites to E.I. DuPont de Nemours & Company v. Synvina
C.V., 904 F.3d 996, 1011 (Fed. Cir. 2018), for the reversal of a Board
decision of non-obviousness where the prior art taught the same oxidation
reaction and taught conditions identical to or overlapping with those of the
claims. (See Appeal Br. 18.) We do not see how this case is persuasive of
Appellant’s argument, where claims were held to be obvious. Appellant
does not point to a statement by the court that obviousness can be
determined only when claims are identical or overlapping with the prior art.
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in kind, not in degree. (Appeal Br. 19, citing Spec. 4:8–20.) Appellant does
not direct us to evidence to support the assertion that this result would have
been unexpected by those of ordinary skill in the art. “Attorney’s argument
in a brief cannot take the place of evidence.” In re Pearson, 494 F.2d 1399,
1405 (CCPA 1974). Nor does Appellant compare the quality of the MRI
results obtained by the claimed emulsion with any of the prior art or direct
us to evidence that 100 mmol is a critical concentration. See In re Baxter
Travenol Labs., 952 F.2d 388, 392 (Fed. Cir. 1991) (“However, when
unexpected results are used as evidence of nonobviousness, the results must
be shown to be unexpected compared with the closest prior art.”).

Conclusion
Upon consideration of the record and for the reasons given, we affirm
the Examiner’s rejection.
In summary:
Claims
Rejected
35 U.S.C.
§
Reference(s)/Basis Affirmed Reversed
1–19 103 Jarzyna, Port 1–19

No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136.

AFFIRMED