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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on September 12, 2025 has been entered.
Status of Claims/Rejections
Claims 1, 5-6, and 34-46 are currently pending in the instant application.
Newly submitted claims 42-46 are directed a non-elected invention. Note that applicant elected claims 1-27 directed to a composition in the reply filed on December 11, 2023.
Since applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claims 42-46 withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
Accordingly, claims 1, 5-6, and 34-41 are under examination on the merits in the instant application.
Any rejections not repeated in this Office action are withdrawn, and the following objections/rejections are the only objections/rejections applied in this application.
Response to Arguments
Applicant’s arguments filed on September 12, 2025 with respect to previous grounds of rejection have been considered but are moot because they do not pertain to the new rejections necessitated by claim amendments as set forth hereinbelow.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed applications, Application Nos. 63/335,485, 63/344,152, 63/390,909, and 63/409,294, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. The aforementioned provisional applications are completely silent regarding SEQ ID NO:3 and SEQ ID NO:4. Accordingly, claims 1, 5-6, and 34-41 are not entitled to the provisional filing date.
Specification
The disclosure is objected to because of the following informalities: The instant specification discloses multiple SEQ ID NOs for the same nucleotide sequence. See for instance SEQ ID NO:3 and SEQ ID NO:5. It is unclear why the same nucleotide sequence is duplicated with two different sequence identifiers. Note that a nucleotide sequence should be identified by a single sequence identifier. Applicant is required to carefully review the entire application and remove any duplicate SEQ ID NOs representing the same nucleotide/amino acid sequences.
Appropriate correction is required.
Claim Objections
Claim 39 is objected to because of the following informalities: “wherein a” in line 1 should be “wherein the”. Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
Claims 1, 5-6, and 34-41 are 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.
Claims 1, 5-6, and 34-41 are now amended to recite a targeting sequence comprising SEQ ID NO:3, which is capable of hybridizing with SEQ ID NO:5.
It is noted that the nucleotide sequence of SEQ ID NO:3 is 5’-CGGGTGCTTGCCATCTT.
It is also noted that the nucleotide sequence of SEQ ID NO:5 is 5’-CGGGTGCTTGCCATCTT.
As such, SEQ ID NO:3 and SEQ ID NO:5 are 100% identical to each other, which therefore means that SEQ ID NO:3 is incapable of hybridizing with SEQ ID NO:5. Hence, the instant claims recite structurally and functionally conflicting, impossible limitations regarding the targeting sequence of the first nanoligomer, thereby rendering the claims indefinite.
Claim 1 recites “the first neuroinflammatory protein includes NLRP3”. The term “includes” means that the protein is not necessarily limited to NLRP3. As such, it is unclear how a single sequence of SEQ ID NO:3 can possibly target multiple neuroinflammatory proteins including NLRP3.
Claim 1 recites “the first neuroinflammatory protein”. However, claim 1 and all of the dependent claims thereof do not recite a “second” neuroinflammatory protein. As such, it is unclear why the recitation of “first” is necessary when there is no subsequent (second, third) number of neuroinflammatory proteins.
Claim 6 recites “wherein the targeting sequences comprise nanostructure binding domains.” However, neither claim 1 nor claim 6 recites “nanostructure”. Hence, it is unclear why “nanostructure binding domains” should be included in the composition of claim 1.
Claim 34 recites “further comprising an embodiment for oral or injectable administration.” It is unclear what is intended and claimed by this limitation as it is incomprehensible. In particular, it is unclear what is meant by “an embodiment”.
Claim 36 recites “a period table”. This limitation is incomprehensible as such term is not recognized in the relevant art.
Claim 37 recites “an Au 22 nanoparticle capped with 18-glutathione molecules”. It is unclear what is meant by “capped”. Note that this term is not even disclosed or defined in the instant specification. As such, it is impossible to clearly determine the metes and bounds of the aforementioned limitation.
Claim 37 recites “configured to maintain spacing”. It is unclear whether “SEQ ID NO: 17” is the structure that provides the recited function “to maintain spacing” or whether other structures are required in order to be “configured” to provide the recited function. For examination purpose, the expressly recited single structure, SEQ ID NO:17, will be interpreted as being the structure that is meant to “maintain spacing”.
Claim 37 recites “peptide nucleic acid (PNA) segments of the polynucleotide binding domain”. It is unclear which of the 17-mer sequence of SEQ ID NO:3 should be the “PNA” segments.
Claim 37 recites the limitation "PNA segment" in in line 10. There is insufficient antecedent basis for this limitation in the claim. It is unclear whether the aforementioned limitation is same as or different from the PNA “segments” recited in line 6.
Claim 37 recites “thereby binding all components together”. It is unclear exactly what is referred to by “all components” as the word “component” or “components” are not recited preceding the aforementioned limitation.
Claims 38-39 recite “configured to decrease microglial and astrocytic inflammation”. However, there is no structural limitation pertaining to the recited function. That is, claims 38-39 fail to particularly point out and distinctly claim what structures of the composition of claim 1 should be required in order to be “configured” to provide the recited function.
Claims 38-39 recite “composition disease progression”. This phrase is not art-recognized and is not defined/described in the specification. Hence, it is impossible to clearly determine the metes and bounds of the aforementioned limitation.
Claim 40 recites “configured to downregulate expression of a gene”. However, there is no structural limitation pertaining to the recited function. That is, claim 40 fails to particularly point out and distinctly claim what structures of the composition of claim 1 should be required in order to be “configured” to provide the recited function.
Claim 40 recites “downregulate expression of a gene”. It is unclear whether “a gene” recited in claim 40 is a gene that is completely unrelated to NLRP3 and NF-kB recited in claim 1. If such is the case, it is unclear what “gene” should be downregulated. Further, if “a gene” should refer to one or both of the expressly recited in claim 1, “a gene” should be amended to particularly point out and distinctly claim the type of “gene” that is downregulated.
Claim 41 recites the limitation "wherein downregulation" in line 1. There is insufficient antecedent basis for this limitation in the claim. Note that the word “downregulation” is not recited in claim 1.
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 claims filed on September 12, 2025 are replete with multiple §112(b) issues as set forth above. This rejection is made only for claims 1, 5, 35, and 38, which are the only claims that can be reasonably interpreted and examined.
Solely in the interest of compact prosecution, the first nanoligomer’s targeting sequence will be interpreted as comprising SEQ ID NO:3 targeting NLRP3, and the “comprising a sequence selected…and 9,” will not be taken into consideration.
Claims 1, 5, 35, and 38 are rejected under 35 U.S.C. 103 as being unpatentable over Saltzman et al. (US 2021/0206879 A1) in view of Zhang et al. (US 2022/0354963 A1) and Dale (US 2008/0119426 A1, of record).
Saltzman teaches making a composition comprising a gold nanoparticle conjugated with “inhibitors of NfKB pathway” and “NLRP3 inhibitor” for immunosuppression, wherein target inhibitors can be an antisense molecule. See paragraphs 0014, 0155-0158, 0242, and 0296.
Saltzman does not teach that the antisense molecule that functions as the NLRP3 inhibitor comprises SEQ ID NO:3 and the antisense molecule that functions as the inhibitor of NfKB comprises SEQ ID NO:4.
Zhang discloses an antisense oligonucleotide of SEQ ID NO:104 (5’-GCGGGTGCTTGCCATCTTCA) targeting human NLRP3, wherein Zhang’s SEQ ID NO:104 comprises the entire 17-mer sequence of SEQ ID NO:3 claimed in the instant case. See the underlined sequence. See Figure 1A.
Zhang teaches that the antisense oligonucleotide can comprise “peptide nucleic acids (PNA)”, which is useful for “improving certain properties of oligonucleotides, such as affinity and/or nuclease resistance.” See paragraphs 0418-0419.
Dale discloses an antisense oligonucleotide of SEQ ID NO:50 (5’-CTGCCATTCTGAAGCCGG) targeting NF-kB-1 (NM_003998) in Table 3, wherein Dale’s SEQ ID NO:50 comprises the entire 17-mer sequence of SEQ ID NO:4 claimed in the instant case. See the underlined sequence.
Dale teaches that the antisense oligonucleotide can comprise “peptide nucleic acids” that “have shown a great promise for oligonucleotides to be used in vivo”. See paragraph 0055.
It would have been obvious to one of ordinary skill in the art before the effective filing date to use Zhang’s SEQ ID NO:104 for the “NLRP3 inhibitor” and Dale’s SEQ ID NO:50 as one of the “inhibitors of NfKB pathway” conjugated to the gold nanoparticle of Saltzman. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success because one of ordinary skill in the art would have readily recognized that Zhang’s SEQ ID NO:104 qualifies as an “antisense molecule” that is the “NLRP3 inhibitor” and Dale’s SEQ ID NO:50 qualifies as an “antisense molecule” that is one of the “inhibitors of NfKB pathway”.
One of ordinary skill in the art would also have been motivated to incorporate peptide nucleic acids (PNA) into each of the prior art’s antisense oligonucleotides of Zhang and Dale so as to improve properties of the antisense oligonucleotides because it was expressly taught by both Zhang and Dale that peptide nucleic acids (PNA) in antisense oligonucleotides are useful for improving “affinity”, “nuclease resistance”, and “in vivo” use of the oligonucleotides.
Since the composition comprising the gold nanoparticle conjugated with the human NLRP3-targeting antisense oligonucleotide of Zhang’ SEQ ID NO:104 and human NF-kB-targeting antisense oligonucleotide of Dale’s SEQ ID NO:50 fully satisfies all structural limitations set forth in the rejected claims, it necessarily follows that the composition rendered obvious in the instant rejection would inherently decrease microglial and astrocytic inflammation as recited in claim 38, absent objective evidence to the contrary.
Note that the Office does not have the facilities and resources to provide the factual evidence needed in order to determine and/or compare the specific activities of the instantly claimed composition to the composition rendered obvious in the instant rejection. In the absence of evidence to the contrary, the burden is upon the applicant to prove that the claimed composition is different from the one rendered obvious in the instant rejection, thereby establishing patentable differences. See In re Best 562F.2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ2d 1922(PTO Bd.Pat. App. & Int. 1989).
In view of the foregoing, claims 1, 5, 35, and 38 taken as a whole would have been prima facie obvious before the effective filing date.
Response to Arguments/Declaration
Applicant's arguments filed on September 12, 2025 have been considered but are moot because they do not pertain to the new rejection set forth above. However, the examiner will address applicant’s non-prior art-related arguments.
Applicant argues that “the composition (SB_NI_112)” shows the specific “results” disclosed in paragraphs 0040-0078 of the specification including the extended lifespan and increased hippocampal neuronal density in mice treated with “SB_NI_112”, wherein such results are not taught by the previously cited art. In response, it is noted that the rejected claims in the instant §103 rejection as well as the non-rejected claims under examination on the merits in the instant application are not directed to “SB_NI_112”, nor are they directed to a method of extending lifespan or increasing hippocampal neurons. Further, the paragraphs pointed out by applicant do not expressly disclose that the composition administered to mice have SEQ ID NO:3 and SEQ ID NO:4 as required by the instantly amended claims. Hence, the results are not commensurate in scope with the rejected claims.
The declaration under 37 CFR 1.132 filed on September 12, 2025 is insufficient to establish nonobviousness of the instantly rejected claims for the following reasons:
The declarant, the sole inventor of this application, states that there are “several points of distinction that demonstrate why my claimed composition is not obvious.” See paragraph 4. The declarant in particular states that the claimed composition provides “results and advantages that would not have been expected” by pointing out 13 references, most of which are post-filing. As an initial matter, it is noted that none of the references cited in the declaration have been cited in the IDS of record, nor has applicant provided a legible copy of each reference for examiner’s full consideration of each of the cited references. Hence, the examiner will solely rely on the reproduced Figures pasted in the declaration.
It appears that none of the Figures in the declaration shows a composition comprising both SEQ ID NO:3 and SEQ ID NO:4 as now claimed. Further, it remains unknown whether the compositions in the Figures, which appear to be called “SB_NI_112” and “NI112”, fully satisfy all structural limitations of the claims rejected in the instant §103 rejection. In fact, it appears that “NI112” is intended to target only NF-kB as evidenced by the Figure legend at page 23 of the declaration. It is noted that the declarant states the “SB_NI_112 is disclosed/presented in claim 1”. See page 25. In response, it is noted that the instant specification discloses “SB_NI_112 human NLRP3” in order to refer to a structure having SEQ ID NO:3-SEQ ID NO:17-SEQ ID NO:18-Au22, Glutathione 18 and “SB_NI_112 human NLRP3” in order to refer to a structure having SEQ ID NO:4-SEQ ID NO:17-SEQ ID NO:18-Au22, Glutathione 18. See Table 1. As such, “claim 1” pointed out by the declarant is far from having the “SB_NI_112” structure.
Now, regarding the results shown in the reproduced Figures, it is noted that the composition claims rejected in the instant rejection do not recite or require any of the effects, nor are the claims have the structural requirements of the “SB_NI_112”. Hence, the unexpected results pointed out by the declarant are not commensurate in scope with the rejected claims.
Note that the “objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support.” See MPEP §716.02. Further, unexpected results must also be “commensurate in scope with the degree of protection sought by the claimed subject matter.” In re Harris, 409 F.3d 1339, 1344 (Fed. Cir. 2005).
Accordingly, the §1.132 declaration is not found sufficient to support the asserted nonobviousness of the rejected claims.
Double Patenting
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.
Claims 1, 5, 35, and 38 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 and 8-24 of copending Application No. 18/079,312 in view of Zhang et al. (US 2022/0354963 A1), Dale (US 2008/0119426 A1, of record), and Lu et al. (International Immunopharmacology, 2019, 67:119-128, of record).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are an obvious variation of the ‘312 claims drawn to a composition comprising two PNAs each targeting NLRP3 and NF-kB, wherein the composition comprises a delivery nanoparticle having a hydrodynamic size of less than 2 nm. It would have been obvious to use Zhang’s SEQ ID NO:104 for the NLRP3-targeting PNA oligonucleotide and Dale’s SEQ ID NO:50 for the NF-kB-targeting PNA oligonucleotide claimed in the ‘312 claims because each of the prior art’s oligonucleotide fully satisfies the structural and functional limitations set forth in the ‘312 claims, wherein it would have been further obvious to utilize the two targets recited in claims 2-3 of the ‘312 claims for enhanced neuroinflammation inhibition because both genes were known to be involved in the neuroinflammation pathway as taught by Lu.
In the remarks filed on September 12, 2025, applicant argues that “a Terminal Disclaimer in compliance with 3 CFR 1.321 (c) or 1.321 (d) was submitted for 18/079,312 to obviate these non-statutory double patenting rejections.” Contrary to applicant’s argument, there does not appear to be any terminal disclaimer filed in this application.
Claims 1, 5-6, and 34-41 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-10, 12-15, 20-21, and 24-33 of copending Application No. 18/376,197 in view of Dale (US 2008/0119426 A1, of record) and Lu et al. (International Immunopharmacology, 2019, 67:119-128, of record).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are an obvious variation of the ‘197 claims drawn to a composition comprising a nanoligomer comprising SEQ ID NO:3 targeting NLRP3 having a hydrodynamic size of less than 2 nm. It would have been obvious to further include Dale’s SEQ ID NO:50 targeting NF-kB, thereby arriving at the instant claims for enhanced neuroinflammation inhibition because both genes were known to be involved in the neuroinflammation pathway as taught by Lu.
Conclusion
No claim is allowed.
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/DANA H SHIN/Primary Examiner, Art Unit 1635