DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election of Group I, claims 61-73, in the reply filed on 7/2/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 61-66 are rejected under 35 U.S.C. 102(a)(1) as anticipated by Freire et al., “Zoledronate complexes. III. Two zoledronate complexes with alkaline earth metals: [Mg(C5H9N2O7P2)2(H2O)2] and [Ca(C5H8N2O7P2)(H2O)]n,” Acta Cryst. C66 (2010), m166–m170 (“Freire”).
Regarding claim 61, Freire discloses crystalline metal-zoledronate compounds, including [Mg(Zol)2(H2O)2] and [Ca(Zol)(H2O)]n, thereby teaching the claimed bioactive Mg²⁺ or Ca²⁺ ions and zoledronate ligand molecules coordinated thereto. The Ca compound, for example, is expressly identified as [Ca(C5H8N2O7P2)(H2O)]. See entire document.
Regarding claim 62, Freire teaches coordination of the metal ions through phosphonate oxygen atoms of zoledronate. In the Ca compound, six oxygen atoms originating from bisphosphonate groups participate in metal coordination.
Regarding claim 63, Freire teaches an extended Ca-zoledronate coordination structure. The Ca coordination polyhedra form Ca₂O₂ chains extending along [010], resulting from chelating-bridging phosphonate oxygen atoms. Thus, Freire teaches at least the claimed one-dimensional chain structure.
Regarding claim 64, Freire's [Mg(Zol)2(H2O)2] has a 1:2 Mg:zoledronate ratio, while [Ca(Zol)(H2O)]n has a 1:1 Ca:zoledronate ratio, each expressly falling within the claimed alternatives.
Regarding claim 65, Freire teaches chelating coordination of zoledronate through its phosphonate oxygen atoms. In the Ca structure, atoms O22 and O32 expressly act in a chelating-bridging mode.
Regarding claim 66, Freire expressly teaches metal-coordinated water. For example, the Ca crystal contains a Ca—O1W bond of 2.4393 Å, establishing coordination of water oxygen O1W to Ca²⁺.
Claims 61 and 67 are rejected under 35 U.S.C. 102(a)(1) as anticipated by Ma et al. “Three M(II)-diphosphonate coordination polymers with N-heterocyclic group (M = Ni, Fe, Mg): Synthesis, characterization and magnetic properties” Synthetic metals 182 (2013) pages 40-48.
Regarding claim 61, Ma discloses a crystalline Mg-risedronate coordination compound having the formula: [Mg3(H2L)2(H2O)4]⋅2H2O where the ligand is derived from risedronic acid. Thus, Ma independently teaches Mg²⁺, one of the expressly recited bioactive metal ions of claim 61, coordinated with risedronate ligand molecules.
Regarding claim 67, Ma further teaches that the Mg-risedronate crystal contains both coordinated water and lattice water, as shown by the formula [Mg3(H2L)2(H2O)4]⋅2H2O. The four waters within the coordination compound are distinguished from the two waters outside the coordination entity. Ma further characterizes the compound as a two-dimensional Mg-risedronate layer structure. Thus, Ma itself supplies both the limitations inherited from claim 61 and the additional lattice-water limitation of claim 67, and therefore anticipates claim 67.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim 72 is rejected under 35 U.S.C. 103 as being unpatentable over Freire et al. in view of Lecouvey et al., “A mild and efficient one-pot synthesis of 1-hydroxymethylene-1,1-bisphosphonic acids. Preparation of new tripod ligands” Tetrahedron Letters 42 (2001), 8475–8478, and Lopez-Mejias et al., US 2021/0317149 A1.
Freire teaches the compound of claim 61 as discussed above, including Mg²⁺ and Ca²⁺ bioactive metal ions coordinated by zoledronate bisphosphonate ligands.
Freire does not teach that the ligand molecule is the particular aromatic bis-HMBP ligand depicted in claim 72.
Lecouvey teaches 1-hydroxymethylene-1,1-bisphosphonic acids (HMBPs), characterized by a P–C–P linkage, and expressly recognizes their high efficiency for binding metal ions. Lecouvey provides a mild procedure in which an acid chloride is reacted with tris(trimethylsilyl) phosphite followed by methanolysis to produce the corresponding HMBP tetraacid.
Significantly, Table 1, entry 10, teaches aromatic compound 3j, prepared from the corresponding aromatic diacid chloride 1j. As shown by the chemical structure in Table 1 on page 2, compound 3j contains two HMBP groups on the same aromatic molecule, i.e., two terminal geminal P–C(OH)–P groups and four phosphorus atoms. Lecouvey reports an 86% yield for 3j. Lecouvey expressly explains that its method permits introduction of two HMBP groups on the same molecule, including in the aromatic series, without observed side products.
Lecouvey does not expressly teach the particular extended aromatic spacer depicted in claim 72.
Lopez-Mejias teaches structurally related extended aromatic bisphosphonate ligands and their formation of crystalline coordination compounds with bioactive metal ions including Ca²⁺, Mg²⁺ and Zn²⁺.
It would have been obvious to one of ordinary skill in the art to employ the extended aromatic bis-HMBP ligand suggested by Lecouvey and Lopez-Mejias in the metal-bisphosphonate coordination compounds of Freire. Lecouvey expressly establishes that two HMBP metal-binding groups can be incorporated into the same aromatic molecule and that HMBP groups efficiently bind metal ions, while Lopez-Mejias establishes that structurally related extended aromatic bisphosphonate ligands form coordination compounds with the same Mg²⁺, Ca²⁺ and Zn²⁺ ions recited in claim 61. One of ordinary skill therefore would have had reason to employ the claim-72 aromatic bis-HMBP ligand as an alternative multidentate bisphosphonate ligand for the known bioactive-metal coordination compounds, with a reasonable expectation of forming the corresponding metal coordination compound.
Claim 73 is rejected under 35 U.S.C. 103 as being unpatentable over Mazur et al., US 2014/0339098 A1.
Mazur teaches metal-organic frameworks comprising metal ions coordinated with α-substituted bisphosphonic-acid ligands and expressly identifies Mg, Ca and Zn among the suitable metals. More particularly, Mazur claims 12 and 20 depict the ligand structure corresponding to the ligand recited in present claim 73. Mazur further teaches preparation of MOFs from its disclosed bisphosphonic acids. Paragraph [0131], for example, describes contacting a bisphosphonic acid with a metal acetate, while paragraph [0132] expressly states that MOFs could be obtained for all of the bisphosphonic acids of Examples 1–15 by the disclosed routes. Mazur therefore teaches the particular ligand required by claim 73 and teaches forming metal coordination compounds/MOFs from its bisphosphonic-acid ligands. Mazur further identifies Mg, Ca and Zn among the metals suitable for such compounds.
It would have been obvious to one of ordinary skill in the art to select Mg²⁺, Ca²⁺ or Zn²⁺ from Mazur's expressly disclosed suitable metal ions for coordination with the expressly disclosed claim-73 bisphosphonic-acid ligand because Mazur teaches those metals for forming its bisphosphonate MOFs and teaches that MOFs can be prepared from all of its disclosed bisphosphonic acids. Such a selection would have constituted the use of expressly identified metal ions for their disclosed metal-coordination function with an expressly disclosed ligand, with a reasonable expectation of obtaining the corresponding coordination compound.
Allowable Subject Matter
Claims 68-71 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TAM M NGUYEN whose telephone number is (571)272-1452. The examiner can normally be reached Mon - Frid.
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/TAM M NGUYEN/Primary Examiner, Art Unit 1771
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