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
This action is in response to the papers filed April 21, 2026.
Claim Amendments
Applicant’s amendment to the claims filed 04/21/2026 is acknowledged.
Claims 5, 7-10, 13, 22-25, 31-70, 72-83, 85-96 have been cancelled.
Claims 1-3, 6, 11-12, 14-15, 17-21, 26-29, 84, and 100 are amended.
Claims 102-108 are newly added.
Claims 1-4, 6, 11-12, 14-21, 26-30, 71, 84, 97-108 are pending.
Claims 26, 71, 97-101 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention.
Claims 1-4, 6, 11-12, 14-21, 27-30, 84, 102-108 are under examination.
Election/Restrictions
The following is a summary of the restriction/election requirements in the application. See the Requirement for Restriction/Election mailed 08/28/2025.
In the reply filed 10/08/2025, applicant elected without traverse:
Group 1, drawn to a composition comprising a nanoparticle;
survival motor neuron 2 (SMN2), as the gene targeted by the antisense oligonucleotide; and
Cas endonuclease targeted to the SMN-2 gene, as the gene editing reagent and target gene thereof.
As previously stated in the Office action mailed 01/23/2026, the nonelected antisense oligonucleotides targeting the survival motor neuron 1 (SMN1) gene and the DMD gene have been rejoined.
Claims 26, 71, 97-101 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 08/28/2025.
Priority
The instant application 17/913,540 was filed on 09/22/2022. This application is a national stage of international application PCT/US2021/027319 filed 04/14/2021, claiming priority based on U.S. Provisional Application No. 63/010,250 filed 04/15/2020.
Withdrawal of Prior Rejections/Objections
Rejections and/or objections not reiterated from the previous Office action mailed 01/23/2026 are hereby withdrawn. The following rejections and/or objections are either newly applied or are reiterated and are the only rejections and/or objections presently applied to the instant application. Applicant’s remarks filed 04/21/2026 have been carefully considered, but are moot in view of the new grounds of rejection necessitated by the amendment to the claims.
Claim Objections
Claims 1, 21, 30 and 84 are objected to because of the following informalities:
The phrase “into cytosol of the fetal cell” in line 11 of claim 1 should be “into the cytosol of the fetal cell” instead.
The phrase “of the fetal cell;” in line 11 of claim 1 should be “of the fetal cell; and” instead.
The phrase “composition of claim 1, the mRNA is transcribed” in claim 21 should be “composition of claim 1, wherein the mRNA is transcribed” instead.
The phrase “into cytosol of the cell of a specific type” in line 10 of claim 84 should be “into the cytosol of the cell of a specific type” instead.
The phrase “a survival motor neuron gene to inhibit alternative splicing of the SMN gene” in claim 30 should be “a survival motor neuron (SMN) gene to inhibit alternative splicing of the SMN gene” instead.
In line 2 of claim 84, the phrase “a nanoparticle; , wherein” “a nanoparticle, wherein” instead.
Appropriate action 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.
Claim 84 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.
This rejection is newly applied.
The limitation “the cell of a specific type” in line 8 of claim 84 lacks antecedent basis. For these reasons, one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-4, 6, 11-12, 14-21, 27-30, 102-108 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
This rejection is newly applied.
Claim 1 recites a nanoparticle comprising an inner region of polymer, metal or liposome and an outer region of a nucleic acid scaffold. Linked to the nucleic acid scaffold includes an antisense oligonucleotide targeting a mRNA transcribed in a fetal cell, and a gene-editing reagent, or nucleic acid encoding thereof, targeting said mRNA transcribed in a fetal cell. Dependent claims 28-29 further define the gene-editing reagent as a Cas endonuclease complexed with a guide RNA as a ribonucleoprotein, wherein the guide RNA targets the Cas endonuclease to the mRNA to inhibit formation of a splicing isoform. This instantly claimed subject matter is not found to have sufficient written description in the application as originally filed.
As described in paragraphs 98-106 and Figures 13-15 of the present application, the specification describes a composition comprising a nanoparticle comprising an outer region coated with a nucleic acid scaffold, wherein antisense oligonucleotides and gene-editing reagents may be linked to said nucleic acid scaffold. The gene editing reagents may include zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), peptide-nucleic acids (PNAs) or a Cas endonuclease (see, paragraph 125), and a Cas9-guide RNA complex hybridizes to the nucleic acids of the scaffold possessing sequence complementary to the guide RNA (see, paragraph 97 and Figure 13). However, the specification is not found to describe gene-editing reagents as targeting the mRNA, which is transcribed in a fetal cell and to inhibit formation of a splicing isoform, as instantly claimed in claims 1, 28-29. Rather, the specification describes said gene-editing reagents as targeting a gene, e.g., for correcting a variant gene that promotes an alternative splicing of mRNA that causes a disease, e.g., by insertion of a donor sequence. See, e.g., paragraphs 10, 22, 35, 37, 83, 87, 123, 125 and 138.
Accordingly, based on the evidence of record, the limitation where the gene-editing reagent is targeted to the mRNA transcribed in a fetal cell and to inhibit formation of a splicing isoform, as instantly claimed in claims 1, 28-29, is not found to have sufficient written description in the original disclosure. Therefore, the claims are rejected under 35 U.S.C. 112(a) for containing new matter. Dependent claims are included in the basis of the rejection because they do not correct the deficiencies of the claim upon which they depend.
Claim Rejections - 35 USC § 103
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.
Claim 84 is rejected under 35 U.S.C. 103 as being unpatentable over WO 2020/014270 A1 to Desai et al., of record; in view of WO 2018/175455 A1 to Mirkin et al.
This rejection is newly applied, necessitated by amendment.
Desai discloses polymeric particles that are functionalized by attaching biomolecules of interest for presentation on the surface of the particles. The polymeric particles may further encapsulate biomolecules for release in vivo. Biomolecules include therapeutic nucleic acids, peptides and proteins, as well as members of a specific-binding pair, such as an antibody. See, e.g., par. 5, 48. The first binding member, e.g., an antibody, may target a second binding member present on the surface of a cell, such as a cancer cell, a stem cell or an immune cell, e.g., T cells, NK cells, dendritic cells, macrophages, neutrophils, myeloid immune cells or B-cells. See, par. 61-63.
The particles are nanoparticles comprising an inner region comprising polymeric core, such as a PLGA core, and an outer region comprising a scaffold of DNA. See, e.g., par. 49-52, 175, 189. See especially, Figure 1A, depicting the multi-functionalization of PLGA microparticles using DNA scaffolds, wherein therapeutic proteins pre-conjugated with DNA strands complementary to scaffolds on particles are assembled on the surface through DNA hybridization. The figure further depicts biomolecules having an antibody structure assembled on the surface through DNA hybridization.
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Accordingly, Desai is found to teach or fairly suggest a composition comprising:
a nanoparticle, wherein the nanoparticle comprises:
an inner region comprising a polymer, and
an outer region comprising a scaffold of nucleic acid; and
a payload carried by the nanoparticle, wherein the payload is linked to the nucleic acid of the scaffold or encapsulated in the inner region of the nanoparticle; and
one or more targeting complexes linked to the nucleic acid of the scaffold, wherein the one or more targeting complexes target the nanoparticles to the cell of a specific type.
Desai does not teach or fairly suggest that the nanoparticle further comprises a plurality of endosomal escape peptides linked to the nucleic acid of the scaffold, wherein the endosomal escape peptides cause release of the nanoparticles into the cytosol of the cell of a specific type, as instantly claimed in claim 84.
Mirkin is relevant prior art for disclosing polymer spherical nucleic acid (SNA) conjugates comprised of a PLGA nanoparticle core and a nucleic acid shell. The nanoparticles comprise PLGA, an agent that facilitates escape of the nanoparticle from an endosome and an oligonucleotide conjugated to the surface of the nanoparticle, wherein the agent is conjugated to the surface of the nanoparticle. Said agent includes endosomal escape peptides. The nanoparticle may further comprise a therapeutic payload encapsulated in the nanoparticle or conjugated to the surface of the nanoparticle, wherein said therapeutic payload includes antibodies. See, par. 7, 16-17, 43, 73-74 (Table 1) and 103.
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to modify the nanoparticle composition of Desai by further including a plurality of endosomal escape peptides linked to the nucleic acid of the scaffold, in view of the teachings of Mirkin, with a reasonable expectation of success because Mirkin teaches decorating the surface of PLGA-SNA nanoparticles with endosomal escape peptides in order to facilitate or enhance release of the nanoparticle from an endosome.
For these reasons, claim 84 would have been prima facie obvious over the prior art.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAMES J GRABER whose telephone number is (571)270-3988. The examiner can normally be reached Monday-Thursday: 9:00 am - 4:00 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James D Schultz can be reached at (571)272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JAMES JOSEPH GRABER/Examiner, Art Unit 1631
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