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 .
Detailed Action
Status of Application
1. Applicants’ arguments/remarks filed 8 May 2026 are acknowledged. Claims 1, 5-9, 15-16, 18-22, 24-28, and 30-48 are currently pending. Claims 2-4, 10-14, 17, 23, and 29 are cancelled. Claims 6-7, 19-21, 24-28, and 30-48 were previously withdrawn. Claims 1, 5, 8, and 16 are amended. Claims 1, 5, 8-9, 15-16, 18, and 22 are examined on the merits within.
Withdrawn Objections/Rejections
2. Applicants’ arguments, filed 8 May 2026, with respect to the claim objections have been fully considered and are persuasive. The objection of claim 14 has been withdrawn. The 35 U.S.C. 112(b) Rejection of claim 5 is withdrawn in view of the claim amendments.
Maintained Rejections
Claim Rejections – 35 U.S.C. 102
3. 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.
4. Claim(s) 1, 5, 8-9, 16, 18, and 22 is/are again rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lin et al. (WO2019028250).
Regarding instant claims 1 and 16, Lin et al. disclose a metal organic layer comprising periodic repeats of metal-based secondary building units and organic bridging ligands, wherein one or more of the secondary building units comprise a metal ion capable of absorbing x-rays. See claim 1. The metal ion capable of absorbing x-rays includes Ba, Ta, W, Re, Os, Ir, Pt, Au, Pb, and Bi or a Hf ion. See claim 2. Example 3 uses a trifluoroacetate capping group. The at least one organic bridging ligand is 5,15(p-benzoato)porphyrin (DBP). See claim 14.
Regarding instant claims 5 and 22, the metal organic layer may comprise an additional therapeutic agent, such as an immunotherapy agent. The agents can be covalently or electrostatically bonded, or sequestered in pores or channels. See page 60.
Regarding instant claims 8-9 and 18 the therapeutic agent may be imiquimod. See page 65.
The organic bridging ligand comprises nitrogen donor moiety. Examples include 4',6'-dibenzoato-[2,2'-bipyridine]-4-carboxylate (BPY), 4'-(4-carboxyphenyl)- [2,2':6',2"-terpyridine]-5,5"-dicarboxylate (TPY), and 4,4'-(2,2'-bipyridine]- 5,5'-diyl)dibenzoate (QPDC). See page 51. Example 7 uses Ir[dF(CF3)ppy]2 Cl Dimer.
Since Lin et al. disclose a metal organic layer comprising periodic repeats of metal-based secondary building units and organic bridging ligands, wherein one or more of the secondary building units comprise a metal ion capable of absorbing x-rays, the physical properties should be the same, i.e., zeta potential of at least about 5 millivolts. Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977).
Thus the instant claims are anticipated by Lin et al.
Claim Rejections – 35 U.S.C. 103
5. 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.
6. Claim(s) 1, 5, 8-9, 15-16, 18, and 22 is/are again rejected under 35 U.S.C. 103 as being unpatentable over Lin et al. (WO2019028250) in view of Ni et al. (Nature Communications, 2018).
Regarding instant claims 1 and 16, Lin et al. teach a metal organic layer comprising periodic repeats of metal-based secondary building units and organic bridging ligands, wherein one or more of the secondary building units comprise a metal ion capable of absorbing x-rays. See claim 1. The metal ion capable of absorbing x-rays includes Ba, Ta, W, Re, Os, Ir, Pt, Au, Pb, and Bi or a Hf ion. See claim 2. Example 3 uses a trifluoroacetate capping group. The at least one organic bridging ligand is 5,15(p-benzoato)porphyrin (DBP). See claim 14.
Regarding instant claims 5 and 22, the metal organic layer may comprise an additional therapeutic agent, such as an immunotherapy agent. The agents can be covalently or electrostatically bonded, or sequestered in pores or channels. See page 60.
Regarding instant claims 8-9 and 18 the therapeutic agent may be imiquimod. See page 65.
The organic bridging ligand comprises nitrogen donor moiety. Examples include 4',6'-dibenzoato-[2,2'-bipyridine]-4-carboxylate (BPY), 4'-(4-carboxyphenyl)- [2,2':6',2"-terpyridine]-5,5"-dicarboxylate (TPY), and 4,4'-(2,2'-bipyridine]- 5,5'-diyl)dibenzoate (QPDC). See page 51. Example 7 uses Ir[dF(CF3)ppy]2 Cl Dimer.
Since Lin et al. teach a metal organic layer comprising periodic repeats of metal-based secondary building units and organic bridging ligands, wherein one or more of the secondary building units comprise a metal ion capable of absorbing x-rays, the physical properties should be the same, i.e., zeta potential of at least about 5 millivolts.
Lin et al. do not teach nanoparticles.
Ni et al. teach selective delivery of photosensitizers to mitochondria of cancer cells that enhance the efficacy of photodynamic therapy. Hf-DBB-Ru is a mitochondria targeted MOF providing strong mitochondria targeting property. See abstract. The particles exhibited a positive zeta potential of 38.9 mV due to the cationic [DBB-RU]2+. See Results. The metal organic frameworks are nanoscale. See abstract. Taken together, Hf-DBB-Ru was efficiently uptaken by tumor cells and internalized into mitochondria due to its small particle size and highly delocalized positive charges on the particle. See page 5. Thus the particles are deemed nanoparticles.
It would have been well within the purview of the skilled artisan to modify the shape to a nanoparticle because Ni et al. teach the effective uptake of particles by mitochondria in the nanometer size.
Double Patenting
7. The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
8. Claims 1, 5, 8-9, 15-16, 18, and 22 are again rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 and 24-25 of U.S. Patent No. 11,826,426.
Although the claims at issue are not identical, they are not patentably distinct from each other because both the instant application and U.S. Patent No. 11,826,426 are directed to metal organic frameworks comprising metal based secondary building units and organic bridging ligands. The only difference lies in the fact that U.S. Patent No. 11,826,426 further claims the thickness of the layer and specific organic bridging ligand. Thus, the invention of the patent is in effect a "species of the "generic" invention of the instant application It has been held that the generic invention is "anticipated" by the "species". See In re Goodman, 29 USPQ2d 2010 (Fed. Cir. 1993). Thus the two are not patentably distinct.
9. Claims 1, 5, 8-9, 15-16, 18, and 22 are again rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 10,806,694.
Although the claims at issue are not identical, they are not patentably distinct from each other because both the instant application and U.S. Patent No. 10,806,694 are directed to metal organic frameworks comprising metal based secondary building units and bridging ligands. The only difference lies in the fact that U.S. Patent No. 10,806,694 further claims hafnium oxo clusters and photosensitizers. Thus, the invention of the patent is in effect a "species of the "generic" invention of the instant application It has been held that the generic invention is "anticipated" by the "species". See In re Goodman, 29 USPQ2d 2010 (Fed. Cir. 1993). Thus the two are not patentably distinct.
Response to Arguments
Applicants’ arguments filed 8 May 2026 have been fully considered but they are not persuasive.
10. Applicants argued, “Lin et al. do not disclose, teach or suggest each and every element of claims 1 and 16.”
In response to applicants’ arguments, it is unclear which element Lin et al. does not teach. Lin et al. disclose a metal organic layer comprising periodic repeats of metal-based secondary building units and organic bridging ligands, wherein one or more of the secondary building units comprise a metal ion capable of absorbing x-rays. See claim 1. The metal ion capable of absorbing x-rays includes a Hf ion. See claim 2. Example 3 uses a trifluoroacetate capping group. The at least one organic bridging ligand is 5,15(p-benzoato)porphyrin (DBP). See claim 14. This reads on the limitations of claims 1 and 16. Applicants’ arguments do not comply with 37 CFR 1.111(c) because they do not clearly point out the patentable novelty which he or she thinks the claims present in view of the state of the art disclosed by the references cited or the objections made. Further, they do not show how the amendments avoid such references or objections.
Thus this rejection is maintained.
11. Applicants argued, “Because the amendments remove a foundational premise of the asserted combination, the stated rationale for combining Lin et al. and Ni et al. no longer accounts for the amended claims as a whole. The instant application shows that TFA modified Hf-DBP leads to improved anti-tumor effect while the anti-tumor effect of Lin et al. is only exhibited in RT-TDT therapy. Ni et al. does not cure the deficiencies.”
In response to applicants’ arguments, even if the claims are no longer directed to DBB as the organic bridging ligands, the prior art of Lin et al. and Ni et al. are similar because both are directed to metal organic frameworks comprising similar components. In particular, both comprise bridging ligands containing a nitrogen donor moiety, i.e., dibenzoato-bipyridine-carboxylate group. Thus Ni et al. is relevant art that makes obvious modifying the size of the particles of Lin et al. with motivation for effective uptake of particles by mitochondria in the nanometer size. With regards to anti-tumor effect, this component is not claimed. However, Lin et al. teach the same combination of ingredients in the same manner and thus should function the same.
Thus this rejection is maintained.
12. Applicants argued, “The Patent Offices attempt to support the nonstatutory obviousness double patenting rejections amount to no more than conclusory arguments.”
In response to applicants’ arguments, U.S. Patent 11,826,426 anticipated the instant invention because both the instant application and U.S. Patent No. 11,826,426 are directed to metal organic frameworks comprising metal based secondary building units and organic bridging ligands. The only difference lies in the fact that U.S. Patent No. 11,826,426 further claims the thickness of the layer and specific organic bridging ligand. Thus, the invention of the patent is in effect a "species of the "generic" invention of the instant application It has been held that the generic invention is "anticipated" by the "species". See In re Goodman, 29 USPQ2d 2010 (Fed. Cir. 1993). U.S. Patent No. 10,806,694 is directed to metal organic frameworks comprising metal based secondary building units and bridging ligands. The only difference lies in the fact that U.S. Patent No. 10,806,694 further claims hafnium oxo clusters and photosensitizers. Thus, the invention of the patent is in effect a "species of the "generic" invention of the instant application. It has been held that the generic invention is "anticipated" by the "species". See In re Goodman, 29 USPQ2d 2010 (Fed. Cir. 1993). This is not a conclusory argument, but instead evidence of anticipation.
Thus this rejection is maintained.
Conclusion
13. THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Correspondence
14. No claims are allowed at this time.
15. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JESSICA WORSHAM whose telephone number is (571)270-7434. The examiner can normally be reached Monday-Friday (8-5).
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/JESSICA WORSHAM/Primary Examiner, Art Unit 1615
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