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
Response to Restriction
Applicants’ election without traverse of Group I (Claims 1-32) and Species of 1) Small molecule immunomodulator and 2) small molecule comprising a phosphate or carboxylate group (claims 8-9 and 18) in the reply filed on 24 December 2025 is acknowledged.
Status of Application
The instant application is a national stage entry of PCT/US2021/033886 filed 24 May 2021. Claims 1-48 are currently pending. Claims 6-7, 19-21, 24-28, and 30-48 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention and species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 24 December 2025. Claims 1-5, 8-18, 22-23, and 29 are examined on the merits within.
Claim Objections
3. Claim 14 is objected to because of the following informalities: “The MOF clam 10” should instead recite “The MOF of claim 10”. Appropriate correction is required.
Claim Rejections – 35 U.S.C. 112(b)
4. The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
5. Claim 5 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
6. Claim 5 recites the limitation "the two- or three-dimensional network" in line 3. There is insufficient antecedent basis for this limitation in the claim. This language is also found in claim 8. Claim 1 however recites “a two- or three-dimensional matrix”.
Claim Rejections – 35 U.S.C. 102
7. 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.
8. Claim(s) 1-5, 8-10, 12-14, 16-18, and 22-23 is/are 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.
Regarding instant claims 2 and 17, 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.
Regarding instant claim 3, Example 3 uses a trifluoroacetate capping group.
Regarding instant claims 4 and 23, 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.
Regarding instant claim 10, 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.
Regarding instant claims 12-13, Example 7 uses Ir[dF(CF3)ppy]2 Cl Dimer.
Regarding instant claim 14, 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
9. 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.
10. Claim(s) 1-5, 8-18, 22-23, and 29 is/are 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.
Regarding instant claims 2 and 17, 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.
Regarding instant claim 3, Example 3 uses a trifluoroacetate capping group.
Regarding instant claims 4 and 23, 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.
Regarding instant claim 10, 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.
Regarding instant claims 12-13, Example 7 uses Ir[dF(CF3)ppy]2 Cl Dimer.
Regarding instant claim 14, 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 or DBB.
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 obvious to one of ordinary skill in the art as of the effective filing date of the invention to substitute one nitrogen donor organic bridging ligand with another to yield predictable results because Ni et al. teach the effectiveness of using DBB in metal organic frameworks to selectively target mitochondria. One would have been motivated, with a reasonable expectation of success, to enhance cancer therapy. The resultant product should have a positive zeta potential due to the cationic [DBB-RU]2+ as taught by Ni et al. 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
11. 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.
12. Claims 1-5, 8-18, 22-23, and 29 are 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.
13. Claims 1-5, 8-18, 22-23, and 29 are 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.
Conclusion
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