Ex Parte Petersen et al

Patent Trials and Appeals Board

Apr 19, 2019

14968019 - (D) (P.T.A.B. Apr. 19, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
14/968,019 12/14/2015 Anncatrine Luisa Petersen
25006 7590 04/23/2019
DINSMORE & SHOHL LLP
900 Wilshire Drive
Suite 300
TROY, MI 48084
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.
16RGSH-H060702PA 8088
EXAMINER
PERREIRA, MELISSA JEAN
ART UNIT PAPER NUMBER
1618
NOTIFICATION DATE DELIVERY MODE
04/23/2019 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):
MichiganPatTM@dinsmore.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte ANNCATRINE LUISA PETERSEN,
JONAS ROSAGER HENRIKSEN,
PALLE HEDENGRAN RASMUSSEN, ANDREAS KJJER,
and
THOMAS LARS ANDRESEN1
Appeal2017-010204
Application 14/968,019
Technology Center 1600
Before DEBORAH KATZ, JOHN G. NEW, and JOHN E. SCHNEIDER,
Administrative Patent Judges.
NEW, Administrative Patent Judge.
DECISION ON APPEAL
1 Appellants identify the Technical University of Denmark and
Rigshospitalet as the real parties-in-interest. App. Br. 3.
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Application 14/968,019
SUMMARY
Appellants file this appeal under 35 U.S.C. § 134(a) from the
Examiner's Final Rejection of claims 39, 41, 47, 49, 51, 52, 54, and 62-74
as unpatentable under 35 U.S.C. § 103(a) as being obvious over the
combination of Farokhzad et al. (US 8,709,483 B2, April 29, 2014)
("Farokhzad"), I. Novak-Hofer et al., Copper-67 as a Therapeutic Nuclide
for Radioimmunotherapy, 29 EUR. J. NucL. MED. 821-30 (2002)
("Novak-Hofer"), Petersen et al. (US 8,920,775 B2, December 30, 2014)
("Petersen"), Haas et al. (US 2013/0259922 Al, October 2, 2013) ("Haas"),
and Sankaram et al. (US 5,993,850, November 30, 1999) ("Sankaram").
We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.
NATURE OF THE CLAIMED INVENTION
Appellants' invention is directed to a class of diagnostic compounds
comprising a novel liposome composition with encapsulated metal entities,
such as radionuclides, for example 61Cu and 64Cu copper isotopes. Abstract.
REPRESENTATIVE CLAIM
Independent claim 39 is representative of the claims on appeal and
recites:
39. A kit sufficient for preparation of a liposome loaded with
a metal cation, said kit comprising:
a) a liposome composition comprising a vesicle forming
component and a nonlipophilic chelator enclosed by the vesicle
forming component; and
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b) a metal cation-containing composition for loading into
the liposome,
wherein the kit does not comprise an ionophore capable of
transporting the metal cation across a lipid bilayer.
App. Br. 19.
ISSUE AND ANALYSIS
We are persuaded by the Examiner's findings and conclusion that the
claims on appeal are prima facie obvious over the combined cited prior art.
We address Appellants' dispositive arguments below.
Issue 1
Appellants argue that the Examiner improperly construed the claims
to include "adding an ionophore for a reaction at a later time." App. Br. 10.
Analysis
The Examiner finds that Farokhzad teaches particles, including, e.g.,
liposomes, having a diameter of less than 100 microns. Ans. 2 ( citing
Farokhzad col. 2, 11. 37-54, col. 14, 11. 44-65). The Examiner finds that
Farokhzad also teaches that its liposomes comprise one or more surfactants,
sugars, lipids, targeting moiety, etc. Id. (citing Farokhzad col. 3, 11. 15-18,
col. 47, 11. 4-12, col. 48, 11. 5-25). The Examiner finds that the surfactants
taught by Farokhzad comprise DPPC and others, and the lipids comprise
cholesterol. Id. at 3 (citing Farokhzad cols. 19-20, 11. 50-15, col. 21, 11.
12-16).
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The Examiner further finds that the liposomes taught by Farokhzad
may further comprise a therapeutic agent, diagnostic agent, etc. Ans. 3
(citing Farokhzad col. 14, 11. 56-67, col. 42, 11. 39-65, col. 44, 11.
45-67). The Examiner finds that Farokhzad teaches that these diagnostic
agents may comprise 67 Cu chelates and Gd chelates, and that these chelates
are used in imaging technologies. Id. ( citing Farokhzad col. 42, 11. 38-65).
The Examiner finds that the therapeutic agent and/or targeting agent can be
associated with the surface of, encapsulated within, surrounded by, and/or
dispersed throughout, the polymer matrix. Id. ( citing Farokhzad col. 2, 11.
55-59).
The Examiner finds that Farokhzad teaches that its liposomes may be
included in a variety of kits comprising one or more of the targeted particles,
with instructions for use. Ans. 3 ( citing Farokhzad cols. 66-67, 11. 31- 29).
The Examiner finds that the kits of Farokhzad generally include one or more
vessels or containers so that some or all of the individual components and
reagents may be separately housed, means for enclosing individual
containers, etc. Id.
Appellants argue that their claimed invention is based, in part, upon
the discovery that a liposome loaded with a metal cation can be prepared
without the use of an ionophore. App. Br. 10. Appellants assert that, in
light of the disclosures of their Specification, one of ordinary skill in the art
would understand that not only do the claimed kits exclude ionophores, but
that later addition of an ionophore to load a metal cation into a liposome is
unnecessary. Id.
Appellants contend that, contrary to the Examiner's finding, the
claims on appeal do not include a method step to exclude an ionophore, but,
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rather, explicitly recite the limitation that: "the kit does not comprise an
ionophore capable of transporting the metal cation across a lipid bilayer."
App. Br. 11 ( quoting claim 39). Appellants argue that the claims thus
expressly omits the inclusion of an ionophore in the claimed kit. Id.
Appellants argue further that the exclusion of an ionophore from the
claims is reinforced by the combination of the limitation of claim 39 quoted
supra in combination with the preamble, which recites: "A kit sufficient for
preparation of a liposome loaded with a metal cation." App. Br. 11.
Appellants dispute the Examiner's finding that: "the instant claims are
drawn to a kit for the preparation of liposomes and the constituents of the
kit. The kit of the instant claims does not exclude adding an ionophore for a
reaction at a later time." App. Br. 11 ( quoting Final Act. 3). According to
Appellants, however, the Examiner's position on the scope of the claims
contravenes the rules of claim construction. Id. Appellants contend that
construing the claim to include this future addition of an element to the
claimed kit to achieve an intended result specifically disavowed by the claim
itself is, allegedly, contrary to the rules of claim construction. Id.
Appellants point to Phillips v. AWH Corp., 415 F.3d 1303 (Fed. Cir. 2005)
as holding that: "the specification may reveal an intentional disclaimer, or
disavowal, of claim scope by the inventor. In that instance as well, the
inventor has dictated the correct claim scope, and the inventor's intention, as
expressed in the specification, is regarded as dispositive." Id. at 11-12
( quoting Phillips, 415 F .3d at 1316). Appellants assert that independent
claim 39 expressly disavows the inclusion of an ionophore in a kit to prepare
a liposome loaded with a metal cation in two separate places in claim 39: (1)
the preamble; and (2) the limitation reciting: "the kit does not comprise an
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ionophore capable of transporting the metal cation across a lipid bilayer."
Id.
Appellants assert that, in this instance, the language of the preamble is
limiting upon the claim. App. Br. 12. Appellants note that our reviewing
court has held that when "the claim drafter chooses to use both the preamble
and the body to define the subject matter of the claimed invention, the
invention so defined, and not some other, is the one the patent protects." Id.
(quoting Bell Comms. Res., Inc. v. Vitalink Comms. Corp., 55 F.3d 615, 620
(Fed. Cir. 1995)). According to Appellants, in claim 39, the preamble
recites structural limitations that bound the scope of the claim, and that the
"sufficient for" limitation requires the contents of the kit alone to result in
the desired metal cation-loaded liposomes. Id.
We are not persuaded by Appellants' arguments. Generally, the
language of the preamble to a claim is not limiting upon the claim: "where a
patentee defines a structurally complete invention in the claim body and uses
the preamble only to state a purpose or intended use for the invention."
Rowe v. Dror, 112 F.3d 473, 478 (Fed. Cir. 1997); see also Catalina Mktg.
Int'!, Inc. v. Coolsavings.com, Inc., 289 F.3d 801, 808 (Fed. Cir. 2002). The
preamble to claim 39 recites: "A kit sufficient for preparation of a liposome
loaded with a metal cation." The preamble thus recites the intended
purpose, or an intended use, of the claim, viz., the preparation of a liposome
loaded with a cation." We do not find that the language of the claim
reciting: "A kit sufficient. .. " imposes a structural limitation on the claimed
kit, because the modifier "sufficient" speaks directly to the intended purpose
of the claimed kit recited in the rest of the preamble: "prepar[ing] a liposome
loaded with a metal cation."
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We do not find, in the body of the claim, any recited method or
process for making, or instructions for making, metal cation-containing
liposomes without an ionophore. Rather, independent claim 39 is directed to
the structural components of the kit itself, i.e., "a liposome composition
comprising a vesicle forming component and a nonlipophilic chelator
enclosed by the vesicle forming component; and ... a metal cation-
containing composition for loading into the liposome." We find that the
recitation of these limitations is sufficient to structurally define the scope of
the claimed kit. We consequently accord the preambular language no
limiting weight on the remainder of the claim.
Similarly, the limitation reciting: "wherein the kit does not comprise
an ionophore capable of transporting the metal cation across a lipid bilayer"
excludes, by its language, the inclusion of ionophores from the contents of
the claimed kit. As such, it speaks negatively to the structural scope of the
claimed kit, i.e., the kit cannot contain ionophores. However, such a
limitation restricting the structure of the claimed kit, or its claimed contents,
does not, by itself, bring into the scope of the claims the preamble's
recitation of: "A kit sufficient for preparation of a liposome loaded with a
metal cation," because the intended purpose recited in the preamble is not, as
we have explained, structurally limiting upon the claim. Simply put,
because any kit containing: "a liposome composition comprising a vesicle
forming component and a nonlipophilic chelator enclosed by the vesicle
forming component; and ... a metal cation-containing composition for
loading into the liposome," and excluding an ionophore would potentially
infringe upon the claimed kit, we cannot include within the scope of the
claim, as Appellants argue, the intended purpose for which the claim is to be
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used, i.e., the preparation of metal cation-containing liposomes without the
use of an ionophore.
Appellants do not dispute that Farokhzad teaches all of the component
parts recited in claim 39, nor do they argue that Farokhzad teaches
ionophores, or the necessity of using ionophores, in construction metal
cation-containing liposomes. Appellants argue that Farokhzad does not
teach the claimed kits, because, Appellants contend, the kits of Farokhzad all
contain liposomes pre-loaded with metallic cations.
We do not agree. Farokhzad teaches, with respect to kits:
A kit may comprise multiple different targeted particles. A kit
may comprise any of a number of additional components or
reagents in any combination. All of the various combinations are
not set forth explicitly but each combination is included in the
scope of the invention.
Farokhzad col. 66, 11. 32-40. Farokhzad thus broadly teaches that a kit can
contain a targeted particle (i.e., a liposome with a marker to recognize a
target) and any number of additional components, e.g., a therapeutic agent or
a metal cation for use in imaging.
Finally, and as we discuss in more detail infra, Petersen expressly
teaches that it was known in the art that liposomes containing metal cations
can be synthesized without the use of ionophores. See Petersen col. 4, 11.
18-24. Therefore, and contrary to Appellants' arguments, a person of
ordinary skill would not necessarily have believed that inclusion of an
ionophore is necessary to the contents of a kit, as recited in claim 39. We
are therefore not persuaded that the Examiner misconstrued Appellants'
independent claim 39, or the claims dependent from it.
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Issue 2
Appellants argue that the Examiner erred by failing to demonstrate a
motivation for a person of ordinary skill in the art to combine the cited
references. App. Br. 13.
Analysis
Appellants argue that nothing in the cited references provides a
motivation to combine Farokhzad, Novak-Hofer, Petersen, Haas, and
Sankaram in the manner suggested by the Examiner. App. Br. 13-14.
Appellants assert that the Examiner's prima facie case of obviousness can be
reduced to two points: (1) kits can separately house components; and (b) the
product or class of products produced by Appellants' claimed kit is already
known and used in the field of imaging and treatment. Id. According to
Appellants, the Examiner has, based upon these two premises, improperly
employed hindsight reasoning to work backwards from Appellants' claims
to conclude that a kit that includes the separate components of a desired
product, and nothing more, would have been obvious. Id.
With respect to the teachings of Farokhzad, Appellants argue that
Farokhzad teaches liposomes and radionuclides in separate, extensive
listings of prospective particles to include in a kit. App. Br. 15 ( citing
Farokhzad col. 2, 1. 51, col. 10, 1. 3; col. 42, 11. 57-67). Appellants contend
that these general teachings of Farokhzad would fail to guide one of ordinary
skill in the art in selecting contents for any particular kit, much less motivate
this person to select a liposome composition as one component for a kit, a
metal cation-containing composition for another component, and to limit the
components of the kit to these with the understanding that the chosen
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compositions would be sufficient for preparing a liposome loaded with a
metal cation. Id.
With respect to Novak-Hofer, Appellants point to the Examiner's
finding that:
[T]he reference of Novak-Hofer was not used to teach of loading
a metal cation into a liposome without the use of ionophores but
was used to teach that 67Cu-TETA chelates and 67Cu-DOTA
chelates were known in the prior art at the time of the invention
wherein the chelates are used for 1magmg and
radioimmunotherapy.
App. Br. 15 ( quoting Final Act. 5). Appellants contend that this teaching of
Novak-Hofer relates solely to an end product known in two fields of uses
(i.e., imaging and radioimmunotherapy). Id. However, Appellants assert,
Novak-Hofer neither teaches nor suggests how to select components to
include in a kit to produce the end product. Id.
With respect to Petersen, Appellants contend that the reference
teaches away from the claimed subject matter. App. Br. 15. According to
Appellants, Petersen teaches the use of an ionophore to load a metal cation
into a liposome. Id. at 15-16 (citing Petersen col. 2, 11. 47-56). Appellants
argue that, because Petersen teaches that an ionophore is necessary, Petersen
cannot be combined with any reference to teach a kit that excludes this
component. Id. at 16. Such an alteration of the teachings of Petersen, argue
Appellants, would impermissibly change the principle of operation of
Petersen's invention. Id. (citing In re Gordon, 733 F.2d 900, 902 (Fed. Cir.
1984); see also MPEP § 2143.0l(V)).
Appellants next argue that the Examiner relies upon Haas and
Sankaram to teach the general principle of the impact of osmolarity in a
process. App. Br. 17 ( citing Final Act. 7). Appellants assert that both Haas
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and Sankaram fail to connect this general principle to the context disclosed
by Appellants' Specification. Id. Appellants argue that, because the
claimed kit is directed to loading a radionuclide into a liposome, the
scientific principle relating to a decrease in the release rate of an active agent
from a liposome is irrelevant to Appellants' claimed invention and, based
upon this principle, one of ordinary skill in the art would not be motivated to
assemble a kit according to Appellants' claims.
We do not find Appellants' arguments persuasive. As an initial
matter, we emphasize again that Appellants' claims are directed to a
composition of matter, viz., a kit containing various components but
excluding ionophores, and not to a method of making a metal ion-containing
liposome without the use of an ionophore.
As we have explained supra, Farokhzad teaches a kit containing the
recited components of claim 29 (the only independent claim), but does not
teach or suggest the use of an ionophore. We disagree with Appellants that
Farokhzad's teachings of metal cations and liposomes are unrelated to each
other, or that they would not guide a person of ordinary skill to combine
these components in a kit. Specifically, Farokhzad teaches that: "The
present invention provides targeted particles comprising a particle [i.e., a
liposome ], one or more targeting moieties, and one or more therapeutic
agents to be delivered to an organ, tissue, cell, and/or intracellular
compartment." Farokhzad col. 2, 11. 21-24. Farokhzad further teaches that:
In some embodiments, the agent to be delivered is a diagnostic
agent. In some embodiments, diagnostic agents include gases;
commercially available imaging agents used in positron
emissions tomography (PET), computer assisted tomography
(CAT), single photon emission computerized tomography, x-ray,
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fluoroscopy, and magnetic resonance imaging (MRI); anti-
emetics; and contrast agents. Examples of suitable materials for
use as contrast agents in MRI include gadolinium chelates, as
well as iron, magnesium, manganese, copper, and chromium
[i.e., metal cations].
Farokhzad col. 42, 11. 39-48 ( emphasis added). Farokhzad thus teaches that
metal cations, a component recited in claim 39, would naturally be included
in a kit with liposome materials, and that Farokhzad broadly teaches such
kits. See supra citing col. 66, 11. 32-40.
The Examiner relies upon the remaining references as teaching more
limited elements recited in the dependent claims. See Ans. 3. Dependent
claim 49, for example, recites: "wherein said chelator is selected from the
group consisting of 1, 4, 7, 1O-tetraazacyclododecane-1,4,7,10-tetraacetic acid
(DOTA), 1,4,8,11-15 tetraazacyclotetradecane-1,4,8,11-tetraacetic acid
(TE TA), 1, 4, 7, 1 O-tetraazacyclododecane-1, 4, 7, 10-tetra( methanephosphonic
acid) (DOTP), cyclam and cyclen." App. Br. 19; see also dependent claims
71, 72 (App. Br. 22-23).
The Examiner relies upon Novak-Hofer as teaching 67 Cu chelates,
such as TETA, DOTA, etc., and copper chelates in 67Cu labelling of
antibodies. Id. (citing Novak-Hofer 823, 824, Figs 2A-F). The Examiner
finds that these chelates are used for imaging and radioimmunotherapy. Id.
at 3-4 (citing Novak-Hofer Abstr., 828).
We note that Farokhzad also teaches that the use of the same chelates
with gadolinium in its liposomes for use in imaging technologies was well
known in the art:
In some embodiments, inventive targeted particles may comprise
a diagnostic agent used in magnetic resonance imaging (MRI),
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such as iron oxide particles or gadolinium complexes.
Gadolinium complexes that have been approved [Carbohydrate
Agents] for clinical use include gadolinium chelates with DTP A
DTPA-BMA, DOTA and HP-D03A (reviewed in Aime et al.,
1998, Chemical Society Reviews, 27:19).
Farokhzad col. 42, 11. 50-56. Farokhzad also teaches that:
Suitable radionuclides for forming the targeted particle of the
invention include but are not limited to 123I 125I 130I 131I 133I
' ' ' ' ' ' 13sr 47Sc n As nse 9oy ssy 97Ru 10opd 101mRh 119Sb 12sBa
' ' ' ' ' ' ' ' ' ' 197Hg 211At 212Bi 212pb 109Pd 111In 67Ga 6sGa 67Cu 7sBr nBr
' ' ' ' ' ' ' ' ' ' ' 99mTc 14c 13N 1s0 32p 33p and 1sp ' ' ' ' ' ' .
Id. at 11. 62-67 ( emphasis added). We consequently agree with the Examiner
that chelating agents like DOTA and TETA were well known in the art at
the time of invention as chelating agents for metal cations, and that they
could be employed in targeted liposomes, as taught by Farokhzad.
The Examiner relies upon Petersen as also teaching a radiolabeled
agent encapsulated in a liposome. See Ans. 4. Petersen expressly teaches
that such radionuclides are Cu(II) cations, e.g., 61 Cu, 64Cu, 67Cu,
Gadolinium, etc., as recited in dependent claims 51 and 63-68 Id. ( citing
Petersen col. 4, 11. 56-64, col. 5, 11. 21-37, col. 12, 11. 13-31).
The Examiner also finds that Petersen teaches that the composition
containing the radionuclide is delivered from the manufacturer in the form of
a (lyophilized) salt or aqueous solution. Id. ( citing Petersen col. 30, 11.
9-22). The Examiner further finds that Petersen teaches that chelating
components includes DOTA, DTPA, etc., as recited in dependent claims 49,
71, and 72. Id. (citing Petersen cols. 18-19).
These teachings of Petersen strongly overlap with those of Farokhzad
quoted supra, and we agree with the Examiner that, for that reason, a person
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of ordinary skill in the art would have found it obvious to combine the
references.
Appellants argue further that, because Petersen teaches that
ionophores are necessary for the synthesis of its liposomes, Petersen
therefore teaches away from Appellants' invention. See App. Br. 15-16.
We do not agree. Petersen teaches: "Entrapment of radionuclides such as
copper isotopes into liposomes by the aqueous phase loading of preformed
liposome can be obtained through use of chemical compounds called
ionophores capable of transporting metal ions across lipid membranes."
Petersen col. 2, 11. 47-51 (emphasis added).
However, Petersen also teaches that:
W0/2006/095234 discloses a peptidomimetic moiety binding to
integrin receptors which can be covalently linked to chelators
which bind radionuclides such as 6°Cu, 62Cu and 67 Cu for various
types of imaging. Methods for preparation of liposomes for MR-
imaging which comprise chelated Tm and Gd are also
mentioned. The method of preparation does not utilize
ionophores.
Petersen col. 4, 11. 18-24 ( emphasis added). In other words, Petersen teaches
that radionuclides, including metallic cations, can be incorporated into
liposomes via ionophores, but that methods were also known in the art for
the synthesis of liposomes incorporating metallic cation isotopes without the
use of ionophores.
A reference teaches away when "a person of ordinary skill, upon
reading the reference, would be discouraged from following the path set out
in the reference, or would be led in a direction divergent from the path that
was taken by the applicant." In re Gurley, 27 F.3d 551, 553 (Fed. Cir.
1994 ). Furthermore: [ t ]he prior art's mere disclosure of more than one
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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." In re Fulton, 391 F.3d 1195, 1201 (Fed. Cir. 2004).
Petersen teaches that metallic cation-containing liposomes can be
synthesized, either with or without ionophores. As such, it does not
constitute a teaching away from Appellants' claimed invention.
We consequently affirm the Examiner's rejection of the claims.
DECISION
The Examiner's rejection of claims 39, 41, 47, 49, 51, 52, 54, and
62-74 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. § l .136(a)(l )(iv).
AFFIRMED
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