Ex Parte Langereis et al

Patent Trial and Appeal Board

Sep 28, 2016

13062550 (P.T.A.B. Sep. 28, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
13/062,550 03/07/2011 Sander Langereis
24737 7590 09/30/2016
PHILIPS INTELLECTUAL PROPERTY & STANDARDS
465 Columbus A venue
Suite 340
Valhalla, NY 10595
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
ATTORNEY DOCKET NO. CONFIRMATION NO.
2008P01120WOUS 5333
EXAMINER
PERREIRA, MELISSA JEAN
ART UNIT PAPER NUMBER
1618
NOTIFICATION DATE DELIVERY MODE
09/30/2016 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):
marianne.fox@philips.com
debbie.henn@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 SANDER LANGEREIS, JOCHEN KEUPP, HOLGER GRUELL,
DIRK BURDINSKI, and DANIELLE BEELEN1
Appeal2014-008198
Application 13/062,550
Technology Center 1600
Before JEFFREYN. FREDMAN, ULRIKE W. JENKS, and
DEVON ZASTROW NEWMAN, Administrative Patent Judges.
NEWMAN, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a carrier
for use in delivery ofbioactive agents, which have been rejected as
anticipated and obvious. We have jurisdiction under 35 U.S.C. § 6(b).
We affirm.
1 Appellants identify the Real Party in Interest as KONINKLIJKE PHILIPS
N.V. App. Br. 4.
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Application 13/062,550
STATEMENT OF THE CASE
Background
The Specification discloses:
In a broad sense, the invention can be described with reference
to a carrier suitable for the localized delivery of a biologically
active agent, such as a drug, comprising a 19F contrast agent.
The 19F contrast agent undergoes a change in detectability upon
its release from the carrier. Particularly, in the state wherein the
19F agent is encapsulated in the carrier, the 19F MR signal of the
contrast agent is spectrally very broad. The 19F contrast agent is
thus hardly detectable. Upon release, however, the 19F contrast
agent becomes detectable, and yields a clear, preferably sharp
signal in 19F magnetic resonance.
5:23-29.
The Issues
Claims 1-19 are on appeal. The following rejections are before us to
review (Ans. 2-7):
A. Claims 1, 3, 4, 8, 9, 12, 15, 17, and 18 are rejected under pre-AIA
35 U.S.C. § 102(b) as anticipated by Unger2 as evidenced by
Keupp. 3
2 Evan C. Unger, U.S. Pat. No. 6,088,613, issued July 11, 2000 ("Unger").
3 J. Keupp and T. Shaeffer, Efficient 19F imaging of Multi-Spectral-Line
Contrast Agents: Aliasing serves to minimize time encoding. 14 PROC. INTL.
Soc. MAG. RESON. MED., 913 (2006) ("Keupp").
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B. Claims 1, 3, 4, 8, 9, and 12-19 are rejected under pre-AIA 35
U.S.C. § 103(a) as obvious over Unger as evidenced by Keupp in
view of Port4 and Bachynsky.5
C. Claims 1-19 are rejected under pre-AIA 35 U.S.C. § 103(a) as
obvious over Terreno6 in view of Lamerichs7 and Port in further
view ofKimura8, Bachynsky, and Dunand. 9
Claim 1 illustrates the subject matter and reads as follows:
1. A carrier adapted for the localized delivery of a biologically
active agent, comprising a shell capable of releasing an
enclosed biologically active agent as a result of a local
stimulus, wherein the shell encloses a 19F MR contrast agent
such that the 19F MR contrast agent undergoes a change in
detectability upon its release from the shell.
App. Br. Claims Appendix, p. 29.
4 Marc Port, WO 2006/032705 A2, published Mar. 30, 2006 ("Port").
5 Nicholas Bachynsky and Woodie Roy, U.S. 7,635,722 Bl ("Bachynsky").
6 Enzo Terreno et al, From Spherical to Osmotically Shrunken Paramagnetic
Liposomes: An Improved Generation of LIPOCEST MRI Agents with Highly
Shifted Water Protons, 46 ANGEW. CHEM. INT. ED., 966-968 (2007)
("Terreno").
7 RudolfM. J. N. Lamerichs et al, WO 2007/141767 A2, published Dec. 13,
2007 ("Lamerichs").
8 Atsuomi Kimura et al, 19F Magnetic resonance imaging of
perjluorooctanoic acid encapsulated in liposome for biodistribution
measurement, 22 MAG. RESON. IMAG., 855-860 (2004) ("Kimura").
9 Frank A. Dunand et al, First 170 NMR Observation of Coordinated Water
on Both Isomers of [Eu(DOTAM)H20}3+: A Direct Access to Water
Exchange and its Role in the Isomerization, 122 J. AM. CHEM. Soc. 1506-
1512 (2000) ("Dunand").
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Application 13/062,550
ANTICIPATION
We select claim 1 as representative of the rejected claims. 37 C.F.R.
§ 41.37(c)(l)(iv).
Where ... the claimed and prior art products are identical or
substantially identical, or are produced by identical or substantially
identical processes, the PTO can require an applicant to prove that the
prior art products do not necessarily or inherently possess the
characteristics of his claimed product. . . . Whether the rejection is
based on 'inherency' under 35 U.S.C. § 102, on 'prima facie
obviousness' under 35 U.S.C. § 103, jointly or alternatively, the
burden of proof is the same, and its fairness is evidenced by the PTO' s
inability to manufacture products or to obtain and compare prior art
products.
In re Best, 562 F.2d 1252, 1255 (CCPA 1977) (emphasis added, footnote
omitted).
The issue on appeal is whether the preponderance of evidence
supports the Examiner's conclusion that Unger in vie\'l/ of Keupp teaches the
carrier of claim 1. After considering the evidence and the arguments, we
conclude that a preponderance of the evidence favors the Examiner's
conclusion. Accordingly, we adopt the Examiner's reasoning (see Grounds
of Rejection, Ans. 2--4), and agree that the Examiner properly found
Appellants' arguments unpersuasive (see Response to Argument, Ans. 12-
16). We provide the following points for emphasis and address the
Appellants' arguments below.
Findings of Fact
1. Unger teaches
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a method of magnetic resonance imaging focused surgical and
therapeutic ultrasound comprising administering a contrast
medium for magnetic resonance imaging comprising gas filled
vesicles to a patient requiring surgery, using said contrast medium
to scan the patient with magnetic resonance imaging to identify the
region of the patient requiring surgery, and applying ultrasound to
the region to carry out surgery.
Unger 4:50-57.
2. Unger teaches "[t]he gas filled vesicles may comprise a therapeutic
which may be released to a localized region of a patient upon
ultrasound." Id. at 4:63---65.
3. Ungerteaches
[t]he present invention comprises a method for controlled delivery
of a therapeutic to a region of a patient using magnetic resonance
imaging focused therapeutic ultrasound comprising administering
to the patient vesicles comprising gas-filled vesicles comprising a
therapeutic compound; monitoring the vesicles using magnetic
resonance imaging to determine the presence of the vesicles in the
region; and rupturing the vesicles using ultrasound to release the
therapeutic in the region.
Id. at 4:66-5:8.
4. Unger teaches "focused or directed ultrasound" is the
application of ultrasound energy to a particular region of the body,
such that the ultrasound energy is concentrated to a selected area or
target zone" or alternatively "magnetic resonance which guides the
ultrasound by visualizing the vesicles and the target zone; and
simultaneous with ultrasound visualizing the disruption of tissues
thereby.
Id. at 7:12-18.
5. Ungerteaches
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[t]he stabilized gas filled vesicles useful in the present invention
are believed to rely on this phase magnetic susceptibility difference
... to provide high performance level magnetic resonance imaging
contrast medium and effective rupture of vesicles of the contrast
medium. The vesicles are formed from ... a matrix of stabilizing
compounds which permit the gas filled vesicles to be established
and thereafter retain their size and shape for the period of time
required to be useful in magnetic resonance imaging. The
compounds also permit rupture of the vesicles at a certain energy
level, which energy is preferably ultrasound energy.
Id. at 9:30-42.
6. Unger teaches "[t]he lipids and polymers employed in preparing the
vesicles of the invention are biocompatible" (Id. at 18:10-11) and
discloses example lipids for use at 19:57-21:31.
7. Unger teaches "[t]argeting ligands directed to endothelial cells are bound
to the surface of the gas filled liposomes. A targeting ligand is a
substance which is bound to a vesicle and directs the vesicle to a
particular cell type such as and not limited to endothelial tissue and/ or
cells." Id. at 27-31.
8. Unger teaches that in an example of the invention
As the vesicles expand during heating they are seen as an increased
region of low signal intensity on the magnetic resonance images
corresponding to the zone of magnetic susceptibility caused by the
vesicles. As the vesicles "pop" this is seen as a transient region of
even more demonstrable hypointensity. Thereafter the vesicles
disappear after they have "popped" and cleared. As the vesicles
pop, the doxorubicin pro-drug is released and activated in the
neoplastic lymph nodes.
Id. at 43:13-21.
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9. Unger discloses perfluorooctylbromide as a gas for use as a contrast
medium in the invention. Id. at 5: 19-24.
10. Keupp discloses that perfluorooctylbromide is a 19F contrast agent.
Keupp at 913, Fig. 1 (legend).
Appellants argue that "the cited portions of Unger ... fail to teach or
suggest at least, 'the shell encloses a 19F MR contrast agent such that the 19F
MR contrast agent undergoes a change in detectability upon its release from
the shell,' as in claim 1." App. Br. 11. Appellants argue that the effect
observed in Unger is instead "a change in [magnetic] susceptibility by
altering the phase of a precursor, (e.g. from a liquid to a gas)" and that
"while the cited portions of Unger may mention a therapeutic released from
a vesicle, there is no teaching or suggestion that a 19F MR contrast agent
undergoes a change in detectability upon its release from the shell." Id. at
11-12.
We are not persuaded that the Examiner erred in finding Unger, as
evidenced by Keupp, anticipates the rejected claims. Unger, as evidenced
by Keupp, teaches perflurooctylebromide encapsulated within liposomes,
which may also include a therapeutic substance, and which may be targeted
toward specific tissues by inclusion of a site-specific ligand bound to the
liposome surface, and that delivery of the therapeutic in the target region is
achieved by rupture of the liposomes through application of ultrasound
energy in at the target tissue region (FF 1-10). Unger teaches that the
liposomes "pop" (e.g. burst), leading to a "transient region of even more
demonstrable hypointensity." (FF 8) Appellants do not explain why the
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increase in hypointensity disclosed in Unger of the very contrast agent
Appellants recite in claim 1 (1 9F) upon the "pop" of the liposomes does not
produce a "change in detectability" upon "release from the shell." That
Unger does not specifically disclose "the precursor 'chang[ing] in
detectability upon its release from the shell'" does not preclude anticipation
because a prior art reference can anticipate a claimed invention even though
it describes the claimed subject matter using different terms. See In re
Schaumann, 572 F.2d 312, 317 (CCPA 1978) "([A]lthough appellants would
have us hold that Hildebrandt fails as an anticipation because it does not
contain a description of the subject matter of the appealed claims, ipsissimis
verb is, we cannot countenance a result which so obviously exhalts [sic] form
over substance.").
Appellants argue that Unger discloses a solid precursor that "may
remain concentrated to a distinct location even after its release and maintain
its detectability. As such, the precursor in the cited portions of Unger would
NOT 'undergo a change in detectability upon its release from the shell,' as
in claim 1." App. Br. 14. In addition, Appellants argue that the temperature
activated precursors disclosed in Unger would experience a change in
susceptibility "upon a phase change NOT 'upon its release from the shell."'
Id.
We are not persuaded. It is not necessary for every embodiment in a
reference to encompass the claimed invention in order for the reference to
anticipate the invention. Instead "the description of a single embodiment of
broadly described subject matter constitutes a description of the invention
for anticipation purposes ... , whereas the same information in a
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specification might not alone be enough to provide a description of that
invention for purposes of adequate disclosure." In re Lukach, 442 F.2d 967,
970 (CCP A 1971 ). Moreover, the scope of claim 1 does not exclude
achieving a change in detectability through altering the phase of the
precursor, and Appellants do not explain or provide evidence to clarify why
the phase change described in Unger that causes the liposomes to burst -
thereby permitting enhanced detection of the encapsulated 19F MR contrast
agent - does not cause an increase in detectability "upon its release from the
shell." Appellants' arguments are insufficient without such evidence. See In
re Geisler, 116 F.3d 1465, 1470 (Fed. Cir. 1997) ("[A]ttomey argument [is]
not the kind of factual evidence that is required to rebut a prima facie case of
obviousness").
Conclusion of Law
We affirm the Examiner's rejection of anticipation by Unger as
evidenced by Keupp. Claims 3, 4, 8, 9, 12, 15, 17, and 18 have not been
argued separately and therefore fall with claim 1. 37 C.F.R.
§ 41.37(c)(l)(iv).
OBVIOUSNESS
Rejection over Unger as evidenced by Keupp in view of Port and Bachynsky
The issue is whether a preponderance of the evidence supports the
Examiner's conclusion that Unger, as evidenced by Keupp, in view of Port
and Bachynsky suggest the carrier of claim 1.
The Examiner provides sound fact-based reasoning for combining
Unger as evidenced by Keupp with Port and Bachynsky. Ans. 4--7. We
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adopt the fact finding and analysis of the Examiner in supplement to our
conclusion discussed above that Unger, as evidenced by Keupp, anticipates
claim 1, from which all claims at issue in this rejection depend.
Appellants rely on their arguments made in response to the
anticipation rejection regarding Unger in view of Keupp (App. Br. 15-16).
For the reasons given above (FF 1-10), we find Unger, as evidenced by
Keupp, anticipates and also renders claim 1 obvious because it teaches every
limitation of claim 1. "[A] determination of anticipation, as well as
obviousness, involves two steps. First is construing the claim, ... followed
by, in the case of anticipation or obviousness, a comparison of the construed
claim to the prior art." Key Pharms. v. Hereon Labs. Corp., 161 F.3d 709,
714 (Fed. Cir. 1998). See also In re McDaniel, 293 F.3d 1379, 1385 (Fed.
Cir. 2002) (citations omitted) ("It is well settled that 'anticipation is the
epitome of obviousness'").
Appellants further argue that both Port and Bachynsky do not discuss
a " 19F MR contrast agent" and "fail to cure the deficiencies of Unger with
respect to claim 1. Id. at 17-18. These arguments are not persuasive in light
of our conclusion that Unger, in view of Keupp, teaches every element of
claim 1.
Conclusion of Law
We affirm the Examiner's rejection of obviousness over Unger,
Keupp, Port, and Bachynsky. Claims 3, 4, 8, 9, and 12-19 have not been
argued separately and therefore fall with claim 1. 37 C.F.R.
§ 41.37(c)(l)(iv).
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Rejection over Terreno in view of Lamerichs and Port in further view of
Kimura, Bachynsky, and Dunand
The issue is whether the preponderance of evidence supports the
Examiner's conclusion that Terreno in view of Lamerichs and Port in further
view of Kimura, Bachynsky, and Dunand suggest the carrier of claim 1.
The Examiner provides sound fact-based reasoning for combining
Terreno in view of Lamerichs and Port with Kimura, Bachynsky, and
Dunand. Ans. 7-12. We adopt the fact finding and analysis of the Examiner
and address the Appellants' arguments below.
Appellants note "it is unclear what reference the Examiner cites as
disclosing 'the shell encloses a 19F MR contrast agent such that the 19F MR
contrast agent undergoes a change in detectability upon its release from the
shell' in claim 1." App. Br. 24. Appellants state "the Examiner cites
Terreno in the present rejection" but argue the portions of Terreno cited by
the Examiner "discuss CEST agents" and that the Examiner admits
"'Terreno et al. does not disclose [a] 19F MR contrast agent."' Id.
According to Appellants, "it follows that the cited portions of Terreno also
fail to teach or suggest at least, 'the 19F MR contrast agent undergoes a
change in detectability upon its release from the shell,' as in claim 1" and
seek reversal of the rejection for this reason. Id.
Appellants further argue that "the cited portions of Lamerichs do not
teach or suggest at least, 'the shell encloses a 19F MR contrast agent such
that the 19F MR contrast agent undergoes a change in detectability upon its
release from the shell,' as in claim 1. Id. at 24--25. Similarly, Appellants
argue that Kimura, Dunand, Port and Bachynsky each "fail to teach or
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suggest, at least, 'a shell capable of releasing an enclosed biologically active
agent as a result of a local stimulus, wherein the shell encloses a 19F MR
contrast agent such that the 19F MR contrast agent undergoes a change in
detectability upon its release from the shell,' as in claim 1." Id. at 25-26.
The Examiner responds to Appellants' arguments with a
comprehensive recitation of the teachings for which each reference was cited
as they relate to claim 1 :
The reference of Terreno ... was used to teach ofLIPOCEST
probes with lipidic films (e.g. DPPC, DSPE-PEG2000) wherein
an amphiphilic metal complex, [Ln(l )] (below) may also be
incorporated in the liposome membrane. The reference of
Lamerichs et al. was used to teach of a lipid shell or polymer
shell filled with a perfluoro-compound or other suitable fluorine
containing particle and a CEST agent. The reference of Port
was used to teach of CEST agents within a liposome
comprising DPPC-PEG2000, DPPC-DSPE-PEG2000
(thermosensitive liposomes). The reference of Bachynsky et al.
\'l/as used to teach that thermosensitive liposomes are small
vesicles composed of lipid phosphatidylcholine moieties
constructed to contain and transport a variety of drugs.
Ans. 17-18.
"Bachynsky et al. teaches that thermosensitive liposomes composed of lipid
phosphatidylcholine moieties dissolve and effectively release their
encapsulated contents (e.g. methotrexate, doxorubicin, etc.) when passing
through an area of heated tissue." Id. at 18. "The reference of Kimura ...
was used to teach of 19F MRI wherein the perfluorooctanoic acid (PFOA) is
encapsulated in a liposome." Id. at 19. "The reference of Dunand ... was
used to teach that lanthanide containing DOT AM complexes have a
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coordination site left open for the coordination of at least one water, such as
[Eu(DOTAM)(H20)]3+." Id.
Appellants' arguments are unpersuasive as the Examiner's rejection is
based on the combined teachings of Lamerichs, Kimura, Dunand, Port, and
Bachynsky. (See Ans. 7, 17-19). We agree with the Examiner's
conclusions because nonobviousness cannot be established by attacking the
references individually when the rejection is predicated upon a combination
of prior art disclosures. In re Merck & Co. Inc., 800 F.2d 1091, 1097 (Fed.
Cir. 1986); see also In re Keller, 642 F.2d413, 426(CCPA1981) (finding
"one cannot show nonobviousness by attacking references individually
where, as here, the rejections are based on combinations of references"
(citations omitted)). Thus, whether Lamerichs, Kimura, Dunand, Port, or
Bachynsky individually fail to teach the 19F MR contrast agent undergoing a
change in detectability upon its release from the shell is not dispositive to the
sufficiency of the rationale underlying the rejection. As stated by the
Examiner, Bachynsky teaches that thermosensitive liposomes can dissolve
and release their encapsulated contents when passing through an area of
tissue. Ans. 18. When the contents are 19F as taught by Kimura (Id.), the
release would necessarily lead to a change in detectability upon release from
the shell.
Accordingly, we find the Examiner sufficiently establishes that an
ordinary artisan reading Lamerichs, Kimura, Dunand, Port, and Bachynsky
would have reasonably expected that the 19F MR contrast agent of
Lamerichs could be incorporated into the LIPOCEST probes of Terreno to
create a two contrast model (e.g., 19F giving a first signal and the CEST
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contrast agent giving a second signal) and that 19F MRI can be directly
encapsulated in a liposome as perfluorooactanoic acid (as taught by
Kimura), and further that a targeting ligand taught by Lamerichs or Port
could be incorporated into the LIPOCEST probes to permit target-specific
binding to a tissue of interest. Ans. 7-12. Such LIPOCEST probes would,
as taught by Bachynsky, be expected to dissolve and release their
encapsulated contents into the tissue of interest. Id. We therefore affirm the
rejection of obviousness over the cited references.
Claims 2-19 have not been argued separately and therefore fall with
claim 1. 37 C.F.R. § 41.37( c )(1 )(iv).
SUMMARY
For the reasons discussed above, we affirm the rejections of
anticipation and obviousness of the claims.
TIME PERIOD FOR RESPONSE
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).
AFFIRMED
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