Dirk Burdinski et al.

Patent Trials and Appeals Board

Dec 3, 2019

13379056 - (D) (P.T.A.B. Dec. 3, 2019)

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.
13/379,056 12/19/2011 Dirk Burdinski 2009P00847WOUS 1013
24737 7590 12/03/2019
PHILIPS INTELLECTUAL PROPERTY & STANDARDS
465 Columbus Avenue
Suite 340
Valhalla, NY 10595
EXAMINER
PERREIRA, MELISSA JEAN
ART UNIT PAPER NUMBER
1618
NOTIFICATION DATE DELIVERY MODE
12/03/2019 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):
katelyn.mulroy@philips.com
marianne.fox@philips.com
patti.demichele@Philips.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
________________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
________________

Ex parte DIRK BURDINSKI, JEROEN A. PIKKEMAAT,
BERTRAND SCHMITT, HOLGER GRUELL, and
SANDER LANGEREIS1
________________

Appeal 2018-007312
Application 13/379,056
Technology Center 1600
________________

Before JOHN G. NEW, SHERIDAN K. SNEDDEN, and
RICHARD J. SMITH, Administrative Patent Judges.

NEW, Administrative Patent Judge.

DECISION ON APPEAL

1We use the word “Appellant” to refer to the “applicant” as defined in 37
C.F.R. § 1.142. Appellant states the real party-in-interest is Koninklijke
Philips Electronics N.V. App. Br. 3.
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SUMMARY
Appellant files this appeal under 35 U.S.C. § 134(a) from the
Examiner’s Final Rejection of claims 1, 3–7, and 9–17. Specifically, claims
1, 3–7, and 9–17 stand rejected as unpatentable under U.S.C. § 103(a) as
being obvious over the combination of Kirpotin et al. (US 5,411,730, May 2,
1995) (“Kirpotin”), Briel et al. (US 2007/0014730 A1, January 18, 2007)
(“Briel”), P. Reimer et al., Ferucarbotran (Resovist): A New Clinically
Approved RES-Specific Contrast Agent for Contrast-Enhanced MRI of the
Liver: Properties, Clinical Development, and Applications, 13 EUR. RADIOL.
1266–76 (2003) (“Reimer”), G. Bottoni, Size Effect on the Time Dependence
of Magnetization of Iron Oxide Particles, 33 IEEE TRANS. MAG. 3049–51
(1997) (“Bottoni”), Markov et al. (WO 2008/0099346 A1, August 21, 2008)
(“Markov”), and Viglianti et al. (US 7,672,704 B2, March 2, 2010)
(“Viglianti”).
Claims 1, 3–7, and 9–17 also stand rejected as unpatentable under
U.S.C. § 103(a) as being obvious over the combination of Briel, Reimer,
Kirpotin, Bottoni, Markov, Viglianti, Fisher et al. (US 7,947,307 B2, May
24, 2011) (“Fisher”), and S. Hashimoto et al., The Measurement of Small
Magnetic Signals from Magnetic Nanoparticles Attached to the Cell Surface
and Surrounding Living Cells Using a General-Purpose SQUID
Magnetometer, 54 PHYS. MED. BIOL. 2571–83 (2009) (“Hashimoto”).
We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.

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NATURE OF THE CLAIMED INVENTION
Appellant’s invention is directed to a composition comprising a shell
structure forming a cavity, wherein said shell structure comprises a drug and
wherein said composition is associated with at least one contrast agent.
Abstr.

REPRESENTATIVE CLAIM
Claim 1 is representative of the claims on appeal and recites:
1. A composition comprising a shell structure forming a
cavity, wherein said shell structure comprises a drug and wherein
said composition is associated with at least one contrast agent;
wherein said shell structure is capable of releasing its contents
into the exterior upon the application of an external stimulus and
wherein said contrast agent comprises magnetic particles
composed of Fe, Co, Ni, Zn or Mn or alloys thereof or oxides of
any of these, preferably composed of Fe2O3 or Fe3O4, which are
capable of being detected by Magnetic Particle Imaging (MPI),
wherein at least more than 5% (w/w) of the magnetic particles
comprised in said contrast agent have a magnetic moment of at
least 10-18 m2A and wherein at least more than 5% (w/w) of said
magnetic particles have a remagnetization time of less than l0
milliseconds per particle and wherein at least more than 5%
(w/w) of said magnetic particles have a size of about 5nm to
50nm, wherein the composition includes a distribution of
magnetic particles that balances between size, remagnetization
time and magnetic moment to support MPI.

App. Br. 22.

ISSUES AND ANALYSES
We agree with, and adopt, the Examiner’s findings and conclusion
that the appealed claims are obvious over the combined cited prior art
references. We address the arguments raised on appeal by Appellant below.
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A. Rejection of the claims over Briel, Reimer, Kirpotin, Bottoni, Markov,
and Viglianti

1. Claims 1, 3–6, and 13–16
Issue 1
Appellant argues the Examiner erred in finding the combined cited
prior art references teach or suggest the limitation of claim 1 reciting:
“wherein at least more than 5% (w/w) of said magnetic particles have a
remagnetization time of less than 10 milliseconds per particle.” App. Br. 8.

Analysis
The Examiner finds that Kirpotin teaches superparamagnetic iron
oxide particles having an effective hydrodynamic diameter in the range of 5–
50 nm. Final Act. 3. The Examiner finds that Kirpotin teaches particles
displaying a magnetic moment greater than 10–15 erg/Gauss, which the
Examiner finds encompasses the claimed 10-18 Am2). Id.
The Examiner finds that Briel teaches polycrystalline magnetic iron
oxide particles (Resovist) in a pharmaceutically acceptable shell (e.g.,
dextran) and the use of these compositions in magnetic particle imaging
(“MPI”). Final Act. 3–4. The Examiner finds that Briel teaches that
Resovist comprises SPIO microparticles (magnetite-Fe3O4/Maghemite-
Fe2O3) coated with carboxydextran, as further evidenced by Reimer. Id. at
4.
The Examiner finds that Appellant’s Specification teaches that the
magnetic particles of the instant claims include Resovist. Final Act. 4
(citing Spec. 31, ll. 2–6). Therefore, the Examiner finds, the 5–50 nm
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dextran-coated iron oxide particles of Kirpotin encompass the Resovist of
the instant claims and have the same properties and are capable of the same
functions, such as at least more than 5% of the dextran-coated particles
having a size about 5 nm to 50 nm. Id.
The Examiner further finds that Bottoni teaches generally that the
variation of the magnetization in the time of the samples, in a magnetic field,
occurs with decreasing size of the particles, and that it would therefore have
been predictable to examine the magnetization of iron oxide particles of
different sizes. Final Act. 4.
Finally, the Examiner finds that Markov teaches that MPI requires
high-performance tracer materials (e.g., Resovist) that are highly magnetic
monodispersed particles with fast remagnetization behavior. Final Act. 4.
The Examiner therefore concludes that, at the time of Appellant’s
invention, it would have been obvious to a person of ordinarily skill in the
art that the remagnetization time of the iron oxide particles is less than 10
milliseconds per particle. Final Act. 4. The Examiner arrives at this
conclusion because Markov teaches that Resovist is a highly magnetic
monodispersed particles with fast remagnetization behavior and because
Bottoni teaches that the variation of the magnetization in the time of the
samples occurs with decreasing size of the particles. Id.
Appellant argues that neither Markov nor Bottoni teach or suggest the
limitation of claim 1 reciting: “wherein at least more than 5% (w/w) of said
magnetic particles have a remagnetization time of less than l0 milliseconds
per particle.” App. Br. 9. Appellant contends that, even assuming,
arguendo, that Markov teaches that Resovist is a highly magnetic
monodispersed particle with fast remagnetization behavior and that Bottoni
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teaches that the variation of the magnetization in the time of the samples
occurs with decreasing size of the particles, the combined teachings of
Markov and Bottoni still do not explicitly or implicitly disclose magnetic
particles having the specific remagnetization time of less than 10
milliseconds. Id. at 10. Instead, argues Appellant, both Markov and Bottoni
are silent with respect to the recited magnetization time of less than 10
milliseconds. Id. Therefore, Appellant asserts, a person of ordinary skill in
the art would have had no suggestion from the cited references to provide a
contrast agent having magnetic particles with a specific remagnetization
time of less than 10 milliseconds per particle. Id.
Furthermore, argues Appellant, a skilled artisan would have no
motivation to combine the teachings of Markov and Bottoni. App. Br. 10.
According to Appellant, Markov concerns magnetic particle separation for
MPI, whereas Bottoni concerns the thermal stability of magnetic particles in
a recording medium. Id. Appellant specifically notes that Bottoni does not
involve the remagnetization activity of a contrast agent, but rather teaches
the magnetic decay of a recording media in the presence of reverse field. Id.
Appellant argues that the teachings of Bottoni with respect to magnetization
decay in the presence of a reverse field to determine thermal stability of the
magnetic particle does not pertain in any way to remagnetization or the
duration of particle remagnetization time. Id. Appellant further argues that
Bottoni also does not disclose that the magnetization differences affect
properties of the magnetic particles for a contrast agent. Id. Appellant
contends that the Examiner has failed to provide any reasonable basis for a
person with ordinary skill in the art to have combined the references. Id.
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Finally, Appellant notes that the Examiner relies upon Reimer as
teaching that Resovist comprises superparamagnetic iron oxide (“SPIO”)
microparticles coated with carboxydextran. App. Br. 12 (citing Final Act. 4)
We are not persuaded by Appellant’s argument. Both Markov and
Reimer teach Resovist as suitable for use in MPI and MRI, including
possessing “fast remagnetization time.” See Bottoni Abstr.; Markov Abstr.,
col. 7, ll. 23–27. Appellant’s Specification expressly discloses Resovist as a
SPIO suitable for the purposes of the claimed invention. Specifically,
Appellant’s Specification discloses that:
Particularly preferred is a combination of MPI and MRI as
mentioned herein above, wherein MPI may preferably be used
upon the induction of a release from the composition to
determine the absolute local particle concentration at a certain
site and wherein MRI may preferably be used to visualize the
drug release event as such. This approach may be carried out with
only one type of contrast agent, which is capable of being
detected by MPI and by MRI, e.g. a contrast agent comprising
magnetic particles of different sizes or different magnetic
moments or remagnetization times such as Resovist, or by
combining typical MPI contrast agents and typical MRI contrast
agents as defined herein above.

Spec. 30–31 (emphasis added). This disclosure is directly reflected in
independent claim 1’s recitation of “wherein the composition includes a
distribution of magnetic particles that balances between size,
remagnetization time and magnetic moment to support MPI.”
We agree with the Examiner that a person of ordinary skill would
understand from the teachings of Reimer and Markov, and from the
disclosure of Appellant’s Specification, that Resovist, which was well
known in the prior art, must necessarily, and thus inherently, possess the
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claimed properties recited in claim 1 of “a distribution of magnetic particles
that balances between size, remagnetization time and magnetic moment to
support MPI,” in which “at least more than 5% (w/w) of said magnetic
particles have a remagnetization time of less than l0 milliseconds per
particle” See Final Act. 4.
With respect to Appellant’s argument that a skilled artisan would have
had no reason to combine Bottoni and Markov because the references are,
impliedly, nonanalogous art, we are similarly not persuaded. Appellant’s
claims recite magnetic particles, preferable composed of iron oxides (i.e.,
Fe2O3 or Fe3O4). Bottoni is directed to determining the dependence of the
thermal stability of the magnetization on the size of iron oxide particles, by
measuring the variation of the magnetization in presence of a reverse field.
Bottoni Abstr. Bottoni teaches that “when the size of the particles decreases,
the thermal stability of the magnetization is progressively weakened, with
increase of magnetization decay, magnetic viscosity and fluctuation field
and decrease of activation volume.” Id. The Examiner relies upon Bottoni’s
teaching that the stability of magnetization is a function of particle size,
which would have been a factor in selecting the claimed size range of iron
oxide particles. See Final Act. 4.
Markov teaches that MPI requires high-performing tracer materials
that are highly magnetic monodispersed particles with fast remagnetization
behavior. Markov Abstr. Specifically, Markov teaches that: “It is therefore
an object of the present invention to provide a method such that improved
magnetic particles result [i.e., with the requisite fast magnetization times],
especially for an application in magnetic particle imaging.” Markov teaches
that: “It is anticipated that, in a particular particle assay, there is a
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relationship between magnetic anisotropy and magnetic moment. In a
mixture of poly-grain iron[ ]oxide particles, e.g.[,] Resovist, particle
magnetic anisotropy will be set by a combination of shape and intrinsic
anisotropy.” Id. at col. 7, ll. 23–27.
Therefore, both Bottoni and Markov are related to the magnetic
stability, and the related remagnetization time of iron oxide particles,
including, in the case of Markov, Resovist. “Two separate tests define the
scope of analogous prior art: (1) whether the art is from the same field of
endeavor, regardless of the problem addressed and, (2) if the reference is not
within the field of the inventor's endeavor, whether the reference still is
reasonably pertinent to the particular problem with which the inventor is
involved.” In re Bigio, 381 F.3d 1320, 1325 (Fed. Cir. 2004). Whereas it is
true that Bottoni is silent with respect to MPI, both references are directed to
the magnetic properties, including remagentization time, of iron oxide
particles, which are recited in Appellant’s claims and are certainly pertinent
to the problem with which the inventor is concerned. Appellant’s argument
that a skilled artisan would not combine the references because they are
nonanalogous art is, consequently, not persuasive.

Issue 2
Appellant argues that the combined cited references neither teach nor
suggest the limitation of claim 1 reciting: “a shell structure forming a cavity,
wherein said shell structure comprises a drug and wherein said composition
is associated with at least one contrast agent compris[ing] metal particles,”
in which “the composition includes a distribution of magnetic particles that
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balances between size, remagnetization time and magnetic moment to
support MPI.” App. Br. 12.

Analysis
Appellant argues that Kirpotin, Briel, Viglianti, Needham, and
Reimer, taken either singly or in combination, fail to teach or suggest at least
a composition which includes “a shell structure forming a cavity, wherein
said shell structure comprises a drug and wherein said composition is
associated with at least one contrast agent compris[ing] metal particles,” in
which “the composition includes a distribution of magnetic particles that
balances between size, remagnetization time and magnetic moment to
support MPI” as recited in independent claim 1. App. Br. 12. According to
Appellant, there is no teaching or suggestion in any of these references that
the magnetic particles may be distributed specifically to balance between
size, remagnetization time and magnetic moment to support MPI. Id. at 13.
Instead, argues Appellant, these references are silent with respect to
balancing a distribution of magnetic particles with respect to size,
remagnetization time and magnetic moment. Id. Appellant asserts that the
Examiner has failed to sufficiently explain how the cited references teach
these specific features, and has therefore failed to establish a prima facie
case of obviousness with respect to these features. Id.
We disagree. Both Markov and Reimer teach Resovist, which
comprises SPIOs suitable for MPI as prior art to Appellant’s claimed
invention. As we have explained, Appellant’s Specification discloses that
Resovist is “a contrast agent comprising magnetic particles of different sizes
or different magnetic moments or remagnetization times.” Spec. 31. We
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therefore agree with the Examiner that a skilled artisan would have known
that Resovist which was known at the time of invention, inherently
possessed the recited qualities. We consequently affirm the Examiner’s
rejection of claims 1, 3–6, and 13–16.

2 Claims 7, 9–12, and 17
Issue
Appellant argues that the Examiner erred because the combined cited
prior art neither teaches nor suggests “administering a composition that is a
carrier for a controlled delivery of a drug” which has a “shell structure [that]
is capable of releasing its contents including the drug into the exterior upon
the application of an external stimulus” and “imaging the composition by
MPI to provide quantitative information concerning a release of the drug and
modifying the application of an external stimulus for releasing a drug from a
carrier based upon quantitative information concerning the release of the
drug acquired by MPI imaging.” App. Br. 14.

Analysis
Appellant relies upon the same arguments presented supra with
respect to claims 1, 36, and 13–16. App. Br. 13. Appellant argues further
that the cited prior art neither teaches nor suggests a method which includes
the features of modifying the application of an external stimulus for
releasing a drug from a carrier based upon quantitative information
concerning the release of the drug acquired by MPI imaging. App. Br. 14.
Appellant argues that the Examiner relies upon Viglianti as teaching
these features. App. Br. 14. According to Appellant, Viglianti teaches that
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the accumulation of the compound of interest may be monitored by magnetic
resonance imaging. Id. Appellant contends that Viglianti teaches only that
treatment variables may be modified to improve the uniformity of drug
delivery based on monitoring of tissue drug concentration distribution. Id.
(citing Viglianti col. 18, ll. 31–37). However, Appellant argues, Viglianti
does not teach or suggest that an external stimulus for releasing a drug from
the carrier may be modified based upon quantitative information concerning
the drug release obtained by MRI imaging. Id.
Nor, Appellant argues, does Kirpotin, upon which the Examiner
relies, teach the disputed limitation. App. Br. 15. Appellant contends that
Kirpotin teaches only that liposomes that encapsulate particles may transport
chemotherapeutic drugs, and that the release of the drugs may be induced by
localized heating. Id. (citing, e.g., Kirpotin cols. 4–5, ll. 55–13). However,
Appellant asserts, Kirpotin is silent with respect to modifying the application
of the external stimulus, such as the localized heating taught by Kirpotin,
based on imaging which provides quantitative information concerning the
release of the drug. Id.
The Examiner responds that Kirpotin teaches that its ferroliposomes
can be induced to release chemotherapeutic agents by “melting” of the
liposome structure at a tumor site via localized heating induced by
application of an oscillating electromagnetic field (i.e., an external stimulus).
The Examiner finds that the proper choice of liposome transition
temperature allows for the release of the therapeutic agent at the desired time
and place via localized heating. Ans. 19.
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The Examiner finds that Viglianti teaches an in vivo method of
monitoring the localization and distribution of a compound of interest to a
desired site in an organism by magnetic resonance imaging. Ans. 19.
The Examiner concludes that it would have been obvious to a person
of ordinary skill in the art to monitor the distribution of a compound of
interest to a desired site (e.g., drug delivery/data acquisition for the control
of a drug delivery process) in an organism by MPI with the ferroliposomes.
Ans. 19. The Examiner arrives at this conclusion because both references
are directed to the release of drugs, contrast agents, etc., from an
envirosensitive liposome to a desired site for the treatment and/or diagnosis
of a disease, and because Viglianti further teaches the advantage of real-time
monitoring of drug delivery and allows for monitoring of liposomal drug
delivery in individual patients, leading to individualized treatment that can
increase overall efficacy which encompasses determining the treatability of a
disease condition in a patient, and/or improving treatment of a patient. Id.
We agree with the Examiner. Kirpotin teaches that:
[M]agnetic particles prepared according to the invention and
encapsulated in liposomes can have an extended lifetime in the
bloodstream. Such particles largely escape the RES clearance
which is the usual fate of injected magnetic particles. Such
liposome encapsulated particles are termed ferroliposomes
herein. In addition to acting as carriers for magnetic particles, the
liposomes serve as vehicles for transport of incorporated
therapeutic agents such as chemotherapeutic drugs. By proper
choice of liposome transition temperature, the therapeutic agent
can be released at the desired time and place by localized heating
induced by application of an oscillating electromagnetic field.

Kirpotin col. 4, ll. 55–68.
Viglianti teaches:
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[M]ethods and compositions … generally relat[ing] to
employing magnetic resonance techniques to monitor drug
delivery in vivo. More particularly, the disclosure relates to the
use of liposomes encapsulating a drug and a contrast agent to
monitor drug delivery to a desired site in vivo by magnetic
resonance imaging techniques.

Specifically, Viglianti teaches that:
Yet another advantage of the present methods and compositions
is the ability to perform real time monitoring of events occurring
in vivo. A researcher can monitor, for example, the accumulation
of liposome compositions at a heated site as the accumulation is
occurring. The only delay is that delay associated with obtaining
(for example, about 0.5–4 minutes, depending on scan settings)
and processing (for example, less than about 3–6 seconds) the
nucleus relaxation times to 40 images.
This ability can be of great benefit in determining the time scale
upon which events are occurring. This can translate into an
estimate of the efficiency with which a given compound of
interest is not only delivered to a site of interest, but also how the
compound behaves once it has been delivered.
Id. at col. 16, ll. 3–46. Viglianti further teaches that:
A Site Can be Heated by Invasive/Noninvasive Techniques
In one aspect of the present disclosure, a site of interest is heated.
Heating of the site of interest leads to the accumulation of
liposome composition at the heated site over a period of time
(FIGS. 2A-2B). Without heating the site of interest, the liposome
might at best diffusely accumulate at the site (particularly if it is
a tumor) for a brief time (FIG. 2E), or not at all (FIG. 2D). The
site can be heated by invasive or noninvasive methods and can
depend on the nature of the site being heated.

Id. at ll. 47–57.
We agree with the Examiner that a person of ordinary skill in the art
would have understood that the combined teachings of Viglianti, Kirpotin,
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and the other cited references teach using the magnetic particles as an
quantitative indicator of the concentration of ferroliposomes at a target site,
via MPI, to provide quantitative information concerning a release of the
drug, and modifying the application of an external stimulus, i.e., "selecting a
liposome transition temperature, for releasing a drug from a carrier based
upon quantitative information concerning the release of the drug acquired by
MPI imaging.
We consequently affirm the Examiner’s rejection of claims 7, 9–12,
and 17.

B. Rejection of the claims over Briel, Reimer, Kirpotin, Bottoni, Markov,
Viglianti, Fisher and Hashimoto

Appellant argues that Fisher and Hashimoto fail to claim the alleged
deficiencies of the remaining references, as argued supra. App. Br. 17–20.
We have explained why we affirm the Examiner’s rejection over Briel,
Reimer, Kirpotin, Bottoni, Markov, and Viglianti, and we incorporate that
reasoning by reference here. We consequently affirm the Examiner’s
rejection of the claims.

DECISION
The Examiner’s rejection of claims 1, 3–7, and 9–15 as unpatentable
under 35 U.S.C. §103(a) is affirmed.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(1). See 37 C.F.R.
§ 1.136(a)(1)(iv).

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AFFIRMED

Claims
Rejected
35 U.S.C.
§
Basis Affirmed Reversed
1, 3–7, 9–15 103(a) Kirpotin, Briel,
Reimer, Bottoni,
Markov, Viglianti
1, 3–7, 9–15
1, 3–7, 9–15 103(a) Kirpotin, Briel,
Reimer, Bottoni,
Markov,
Viglianti,
Fisher,
Hashimoto
1, 3–7, 9–15
Overall
Outcome
1, 3–7, 9–15