Ex Parte Horcajada-Cortes et al

Patent Trial and Appeal Board

Mar 27, 2017

12680330 (P.T.A.B. Mar. 27, 2017)

United States Patent and Trademark Office
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O.Box 1450
Alexandria, Virginia 22313-1450
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APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
12/680,330 05/24/2010 Patricia Horcajada-Cortes 021305-00310 3603
4372 7590 03/29/2017
ARENT FOX LLP
1717 K Street, NW
WASHINGTON, DC 20006-5344
EXAMINER
PIPIC, ALMA
ART UNIT PAPER NUMBER
1617
NOTIFICATION DATE DELIVERY MODE
03/29/2017 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):
patentdocket @ arentfox. com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte PATRICIA HORCAJADA-CORTES, GERARD FEREY,
CHRISTIAN SERRE, RUXANDRA GREF, and PATRICK COUVREUR1
Appeal 2016-001728
Application 12/680,330
Technology Center 1600
Before TAWEN CHANG, RYAN H. FLAX, and
RACHEL H. TOWNSEND, Administrative Patent Judges.
FLAX, Administrative Patent Judge.
DECISION ON APPEAL
This is a decision on appeal under 35 U.S.C. § 134(a) involving
claims directed to a product for therapeutic and/or cosmetic use comprising
an isoreticular porous crystalline metal organic framework (MOF) solid.
Claims 1—3, 6, 8, 11—14, 16, and 17 are on appeal as rejected under
35 U.S.C. § 103(a). We have jurisdiction under 35 U.S.C. § 6(b).
We affirm.
1 We understand the Real Parties in Interest to be CENTRE NATIONAL DE
LA RECHERCHE SCIENTIFIQUE (CNRS) and UNIVERSITE DE
VERSAILLES - SAINTQUENTIN-EN-YVELINES. Br. 1.
Appeal 2016-001728
Application 12/680,330
STATEMENT OF THE CASE
The Specification discloses:
The MOF [metal-organic framework] solid of the present
invention may be used, for example, as a contrast agent and/or
for carrying pharmaceutical compounds. The solid of the present
invention may also be used for applications in the cosmetics
field. It may also be used for vectorizing and/or monitoring
pharmaceutical compounds in a body. It may be, for example, in
the form of crystals, powders, particles or nanoparticles.
Spec. 1:10-17.
The appealed claims can be found in the Claims Appendix of the
Appeal Brief. Claim 1 is the sole independent claim, is representative, and
reads as follows:
1. A product for therapeutic and/or cosmetic use comprising an
isoreticular porous crystalline metal organic framework (MOF)
solid comprising a three-dimensional succession of units having
formula (I) below:
MmOkXiLp
Formula (I)
in which:
each occurrence of M independently represents a metal ion
selected from the group consisting of Fe2+, Fe3+, Zn2+, Ti3+, Ti4+,
Zr2+, Zr4+, Ca2+, Cu2+, Gd3+, Mg2+, Mn2+, Mn3+, Mn4+, and Si4+;
- O is an oxygen atom;
- m and p are independently 1, 2, or 3, and k and 1 are
independently 0 or 1;
- X is a ligand selected from the group consisting of OH',
Cl', F", I', Br, S042', NOy, C104', ^-(COOy, R1-(S03y,
and R1-(P03)n', in which R1 is a hydrogen atom, a linear or
branched Ci to Cg alkyl, and n = 1 to 6;
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Application 12/680,330
- L is a spacer ligand comprising a radical R bearing q
groups A, in which
• q is 1, 2, 3, 4, 5 or 6;
• each occurrence of A is independently:
(i) a carboxylate
#
O •
#
o
II #
-p—0
(ii) a phosphonate ORA1 •
#
0
II #*—$—0
1
(iii) a sulfonate ®
*—N—RA2
(iv) an amino group ^A1 ;
#
*—C=N—
.1
(v) an imino group RA1
#
O
#
*—C—N—R*2
I
(vi) an amido group ^A1 ;
U
Q
#
(vii) a carboxyamido group * ^ ^2;
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Application 12/680,330
(viii) a pyridyl group
(ix) a pyridyl oxide group
*
â– O#
(x) an imidazolyl group * \==J ;
in which * denotes the point of attachment of the group A
to the radical R;
# denotes the possible points of attachment of the group A
to the metal ion M;
wherein RA1 and RA2 are independently a hydrogen atom,
a linear, branched or cyclic, optionally substituted Ci.^alkyl,
C2-i2alkene or C2-i2alkyne radical, or an optionally branched
and/or substituted monocyclic or polycyclic aryl comprising 6 to
50 carbon atoms;
• R represents:
(i) aCi -12 alkyl, C2-12 alkene or C2-12 alkyne radical,
(ii) a fused or non-fused monocyclic or polycyclic aryl
radical, comprising 6 to 50 carbon atoms;
(iii) a fused or non-fused monocyclic or polycyclic
heteroaryl, comprising 1 to 50 carbon atoms; or
(iv) an organic radical comprising a metal element
selected from the group consisting of ferrocene, porphyrin,
phthalocyanin and a Schiff’s base
:X1
\
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Application 12/680,330
in which Rxl and Rx2 are independently a hydrogen
atom, a linear, branched or cyclic, optionally substituted
Cm2 alkyl, C2-12 alkene or C2-12 alkyne radical, or an
optionally branched and/or substituted monocyclic or
polycyclic aryl comprising 6 to 50 carbon atoms;
and Rx3 is a linear, branched or cyclic, optionally
substituted Cm2 alkyl, C2-12 alkene or C2-12 alkyne radical,
or an optionally branched and/or substituted monocyclic
or polycyclic aryl comprising 6 to 50 carbon atoms;
the radical R being optionally substituted with one or more
groups R2 independently selected from the group consisting of
Ci-ioalkyl; C2-ioalkene; C2-ioalkyne; C3-iocycloalkyl;
Ci-ioheteroalkyl; Ci-iohaloalkyl; Cs-ioaryl; C3-ioheteroaryl;
C5-2oheterocycle; Ci-ioalkylC6-ioaryl; Ci-ioalkylC3-ioheteroaryl;
Ci-ioalkoxy; Cs-ioaryloxy; C3-ioheteroalkoxy; C3-ioheteroaryloxy;
Ci-ioalkylthio; Cs-ioarylthio; Ci-ioheteroalkylthio;
C3.ioheteroarylthio; F; Cl; Br; I; -N02; -CN; -CF3; -CH2CF3;
-CHC12; -OH; -CH2OH; -CH2CH2OH; -NH2; -CH2NH2;
-NHCOH; -COOH; -CONH2; -S03H; -CH2S02CH3; -P03H2;
-B(ORG1)2; or a function -GRG1 in which G is -0-, -S-, -NRG2-,
-C(=0)-, -S(=0)-, -S02-, -C(=0)0-, -C(=0)NRG2-, -OC(=0)-,
-NRG2C(=0)-, -0C(=0)0-, -OC(=0)NRG2-, -NRG2C(=0)0-,
-NRG2C(=0)NRG2-, -C(=S)-, -C(=S)S-, -SC(=S)-, -SC(=S)S-,
-C(=NRG2)-, -C(=NRG2)0-, -C(=NRG2)NRG3-, -OC(=NRG2)-,
-NRG2C(=NR°3)-, -NRG2S02-, -NRG2S02NRG3-, -NRG2C(=S)-,
-SC(=S)NRG2-, -NRG2C(=S)S-, -NRG2C(=S)NRG2-,
-SC(=NRG2)-, -C(=S)NRG2-, -OC(=S)NRG2-, -NRG2C(=S)0-,
-SC(=0)NRG2-, -NRG2C(=0)S-, -C(=0)S-, -SC(=0)-,
-SC(=0)S-, -C(=S)0-, -OC(=S)-, -OC(=S)0- and -S02NRG2-,
wherein when G is a divalent functional group, the radical R is
attached by one bond and RG1 is attached by the other bond, and
in which each occurrence of RG1, RG2 and RG3 is, independently
of the other occurrences of RG1, a hydrogen atom; a halogen
atom; or a linear, branched or cyclic, optionally substituted
Ci-i2alkyl, Ci-i2heteroalkyl, C2-ioalkene or C2-ioalkyne group; or
a group C6-ioaryl, C3-ioheteroaryl, Cs-ioheterocycle, Ci-ioalkylCs-
ioaryl or Ci-ioalkylC3-ioheteroaryl in which the aryl, heteroaryl or
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Application 12/680,330
heterocyclic radical is optionally substituted; or alternatively,
when G represents -NRG2-, RG1 and RG2 together with the
nitrogen atom to which they are attached form an optionally
substituted heterocycle or heteroaryl;
in which the surface is modified by adsorption, covalent
bonding, hydrogen bonding, Van der Waals bonding and/or
electrostatic interaction of at least one biocompatible organic
surface agent selected from the group consisting of an
oligosaccharide, a polysaccharide, a glycosaminoglycan, a
polymer, a vitamin, a coenzyme, an antibody or antibody
fragment, an amino acid or a peptide, so that the biodistribution,
bioadhesion, targeting and/or vectorization properties of the
surface of the MOF solid are altered for therapeutic and/or
cosmetic use.
Br. 17—20 (Claims App’x).
The following rejections are on appeal:
Claims 1—3, 6, 8, 11, 12, and 14 stand rejected under 35 U.S.C.
§ 103(a) over Francis,2 Horcajada,3 Horres,4 and Martens.5 Final Action 4.
Claims 1—3, 6, 8, 11, 13, 14, 16, and 17 stand rejected under 35 U.S.C
§ 103(a) over Francis, Horcajada, Ragheb,6 Horres, and Martens. Id. at 10.
2 U.S. Patent Application Pub. No. US 2007/0259017 A1 (published Nov. 8,
2007) (hereinafter “Francis”).
3 Patricia Horcajada et al., Metal-Organic Frameworks as Efficient
Materials for Drug Delivery, 45 Angew. Chem. Int. 5974—78 (2006)
(hereinafter “Horcajada”).
4 U.S. Patent Application Pub. No. US 2005/0060028 Al (published Mar.
17, 2005) (hereinafter “Horres”).
5 U.S. Patent No. US 8,512,734 B2 (issued Aug. 20, 2013 to Martens et al.)
(hereinafter “Martens”).
6 U.S. Patent No. US 6,730,064 B2 (issued May 4, 2004 to Ragheb et al.)
(hereinafter “Ragheb”).
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Application 12/680,330
DISCUSSION
We adopt the Examiner’s findings of fact, reasoning on scope and
content of the prior art, and conclusions set out in the Final Action and
Answer. We find the Examiner has established that the claims would have
been obvious over Francis, Horcajada, Horres, and Martens, and also
Ragheb, where relevant.
The Examiner identified the claimed invention as encompassing
porous nanoparticles of an MOF comprising a three dimensional succession
of units of Fe33+0(OH)[l,3,5-benzentricarboxylic acid]2, having a peptide-
modified surface (e.g., via Van der Waals and/or hydrogen bonding), and
where the pores in the MOF contain busulfan. Final Action 4.
The Examiner looks to Francis as disclosing drug-delivering zeolite
structures that can be loaded with, inter alia, anti-proliferative agents,
proteins, enzymes, and vitamins, and combinations thereof, for therapeutic
delivery. Final Action 4—5. The Examiner combined Horcajada with
Francis to replace the zeolite structures of Francis with an MOF structure
because Horcajada discloses MOFs are more capable drug delivery devices
as compared to zeolites or biocompatible dendritic macromolecules/
polymers. Id. at 5—6. The Examiner identified an MOF disclosed by
Horcajada called MIF-100, which is Cr3m0(0H)(H20)2[ 1,3,5-benzene
tricarboxylic acid]2, which was disclosed by Horcajada as loaded with
ibuprofen for therapeutic delivery. Id. at 6.7 The Examiner identified that
Horcajada disclosed that the Cr3+ of MIF-100 is toxic and, thus, undesirable,
7 MIF-100 is disclosed in the Spec, as an example of a suitable MOF for
Appellants’ invention. See, e.g., Spec. 39:18—22.
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Application 12/680,330
and suggested it can be replaced with Fe3+. Id. The Examiner determined
that the Francis protein added to the Horcajada MIL-100 MOF would have
“necessarily interacted with the surface of [the] MOF particles via at least
hydrogen bonding and Van der Waals bo[n]ding or forces” because “[t]he
MOF surface contains carboxylate moieties that would have interacted with
N-H groups that are present in the amide linkages that occur in a protein.”
Id. at 7.
The Examiner added Horres to the prior art combination for disclosing
the anti-proliferative agent busulfan for drug delivery via stents. Id. at 6.
We note the reference also discloses ibuprofen for the same purpose,
establishing the two drugs are interchangeable for this purpose, not
considering desired therapeutic effect. See Horres 117. The Examiner
added Martens to the prior art combination for its disclosure of drug-delivery
particles (zeolites) where drug delivery is regulated by pore size or size of
the drug-delivering particles. Final Action 9. The Examiner added Ragheb
to the prior art combination for its disclosure of rhodamine 123 as a suitable
bioactive agent for delivery via a stent. Id. at 16.
Appellants have not produced evidence showing, or persuasively
argued, that the Examiner’s determination of obviousness is incorrect. Only
those arguments made by Appellants in the Briefs have been considered in
this Decision. Arguments not presented in the Briefs are waived. See
37 C.F.R. § 41.37(c)(l)(iv) (2015). We address Appellants’ arguments
below.
Appellants contend the Examiner’s rejection fails because none of the
cited prior art discloses or suggests the recited modified surface. Br. 11.
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Application 12/680,330
Appellants argue more specifically that Francis and Horcajada do not
disclose an MOF with a surface modified as recited by claim 1. Id. at 13—
14.
With respect to the surface modification claim element, the Examiner
identifies that the rejection is not based on the references individually, but on
the combined references, and that the protein molecules of Francis added to
the MOF particles of Horcajada would necessarily result in the surface
modification recited by the claims. Ans. 17. The Examiner identifies that
the rejection is premised on the inherent properties that result from
combining the proteins of Francis with the MOF of Horcajada. Id.
Appellants did not respond to this contention, but argued that the
combination would not have been made (see infra) and, so, the surface
modification would not occur.
We find the Examiner has the better position. “Non-obviousness
cannot be established by attacking references individually where the
rejection is based upon the teachings of a combination of references.” In re
Merck & Co., 800 F.2d 1091, 1097 (Fed. Cir. 1986). Here, Francis and
Horcajada are combined, so the argument that neither individually discloses
a claim limitation is not persuasive. The Examiner has explained why
combining the proteins of Francis with the MOF of Horcajada would
necessarily result in the recited modified surface and Appellants have not
argued that the Examiner’s reasoning is incorrect.
Appellants argue that the skilled artisan would not have substituted
Horcajada’s MOFs for Francis’s zeolites, as determined by the Examiner.
Br. 12. Appellants contend Francis requires the use of zeolites to satisfy
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Application 12/680,330
Francis’s professed objective of not using co-solvents to incorporate the
drug into its carrying coating and that zeolites are necessary to act as drug
reservoirs with releasing agents to withhold drug release until a triggering
condition. Id. at 12—13. Appellants contend that because zeolites are known
to be stable in body fluids and MOFs are known to degrade more quickly in
body fluids, the two are not interchangeable in a controlled-drug-release
structure. Id. at 13 (citing Thomassen8 and Cunha9).
With respect to Appellants’ argument regarding replacing zeolites
with MOFs, the Examiner responds that Cunha and Thomassen, cited by
Appellants as evidence of divergent stability properties of zeolites and
MOFs, were not published as of the effective date10 of Appellants’
application and, so, could not have been considered by the skilled artisan
when considering combining Francis and Horcajada. Ans. 17. Further, the
Examiner identified that the combination of Francis and Horcajada is
suggested by Horcajada because it “teaches the benefits of using MOFs
compared to zeolites for the purpose of delivering drugs.” Id. at 16.
Appellants did not persuasively respond to these points.
We find the Examiner has the better position. As determined by the
Examiner, Horcajada provides ample reason and motivation to combine its
MOF with Francis’s actives for delivery — Horcajada teaches that its MOFs
8 L. Thomassen et al., Investigation of the Cytotoxicity of Nanozeolites A and
Y, 6 Nanotoxicology 472-85, Abstract (2011).
9 D. Cunha et al., Rationale of Drug Encapulation and Release from
Biocompatible Porous Metal-Organic Frameworks, 25 Chem. Mat. 2161-
lb (2013).
10 The effective filing date of the appealed application is March 26, 2010; the
actual filing date was May 24, 2010.
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Application 12/680,330
are better than Francis’s zeolites for drug delivery. Further, while it would
have been possible for the skilled artisan to consult Francis and Horcajada as
of the application’s effective date, as identified by the Examiner, this would
not have been possible for Thomassen and Cunha because they were not yet
published; thus, Thomassen and Cunha could not have dissuaded the skilled
artisan from combining the references as Appellants argue.
Appellants argue Martens’s disclosure of particle sizes of zeolites
within the claimed range is immaterial because “the presently-claimed
MOFs are not zeolites as they do not contain A1 as the metal center.” Br. 14.
The Examiner responds to this argument by identifying that Martens
suggests the claimed particle size for any particles intended for drug delivery
via a stent and teaches that particle size and pore size affect drug delivery
rate. Ans. 18. Appellants did not persuasively respond to this.
We find the Examiner has the better position. Martens teaches that
pore size and particle size are optimizable variables for drug delivery
particles; thus, its disclosure of these variables is relevant in combination
with other drug delivery particles. Moreover, Marten’s disclosure of these
variables overlaps the claim elements and, so, renders the claim elements
obvious.
Appellants argue that “Ragheb does not relate to MOFs and, therefore,
does not remedy the deficiencies of’ the other references. Br. 15.
The Examiner did not respond to this argument. However, the fact
that Ragheb does not disclose other claim elements (other than delivery of
rhodamine 123) is immaterial here because the Examiner has established
that the other cited references cover the other claim elements.
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SUMMARY
The obviousness rejections of claims 1—3, 6, 8, 11—14, 16, and 17 are
affirmed.
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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