Ex Parte Horcajada-Cortes et alDownload PDFPatent Trial and Appeal BoardMar 27, 201712680330 (P.T.A.B. Mar. 27, 2017) Copy Citation 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. 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; 2 Appeal 2016-001728 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; 3 Appeal 2016-001728 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 \ 4 Appeal 2016-001728 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 5 Appeal 2016-001728 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 “Francisâ€). 3 Patricia Horcajada et al., Metal-Organic Frameworks as Efficient Materials for Drug Delivery, 45 Angew. Chem. Int. 5974—78 (2006) (hereinafter “Horcajadaâ€). 4 U.S. Patent Application Pub. No. US 2005/0060028 Al (published Mar. 17, 2005) (hereinafter “Horresâ€). 5 U.S. Patent No. US 8,512,734 B2 (issued Aug. 20, 2013 to Martens et al.) (hereinafter “Martensâ€). 6 U.S. Patent No. US 6,730,064 B2 (issued May 4, 2004 to Ragheb et al.) (hereinafter “Raghebâ€). 6 Appeal 2016-001728 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. 7 Appeal 2016-001728 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. 8 Appeal 2016-001728 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 9 Appeal 2016-001728 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. 10 Appeal 2016-001728 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. 11 Appeal 2016-001728 Application 12/680,330 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 12 Copy with citationCopy as parenthetical citation