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 Office Action is a response to Applicant’s Election filed May 21, 2026.
Claims 1, 2, 5, 12, 20, 24, 27, 39, 41, 42, 44, 46, 47, 49, 51, 54, 56-58, 61, 63, 66, 69 and 74-76 are pending in the instant application.
Election/Restrictions
Applicant’s election of Group I in the reply filed on May 21, 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)).
Claims 63, 66, 69, 74 and 75 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
The requirement is still deemed proper and is therefore made FINAL.
Accordingly, claims 1, 2, 5, 12, 20, 24, 27, 39, 41, 42, 44, 46, 47, 49, 51, 54, 56-58, 61 and 76 have been examined on the merits as detailed below:
Information Disclosure Statement
Applicant’s information disclosure statement (IDS) filed May 21, 2026 is acknowledged. The submission is in compliance with the provisions of 37 CFR §1.97. Accordingly, the Examiner has considered the information disclosure statement, and a signed copy is enclosed herewith.
Applicant’s IDS filed April 19, 2024 (4 pages) is acknowledged. The submission is in compliance with the provisions of 37 CFR §1.97. Accordingly, the Examiner has considered the information disclosure statement, and a signed copy is enclosed herewith.
Applicant’s IDS filed April 19, 2024 (38 pages) is acknowledged. The submission is in compliance with the provisions of 37 CFR §1.97. Accordingly, the Examiner has considered the information disclosure statement, and a signed copy is enclosed herewith.
Applicant’s IDS filed April 19, 2024 (8 pages) is acknowledged. The submission is in compliance with the provisions of 37 CFR §1.97. Accordingly, the Examiner has considered the information disclosure statement, and a signed copy is enclosed herewith.
Applicant’s IDS filed April 19, 2024 (8 pages) is acknowledged. The submission is in compliance with the provisions of 37 CFR §1.97. Accordingly, the Examiner has considered the information disclosure statement, and a signed copy is enclosed herewith.
Applicant’s IDS filed April 19, 2024 (8 pages) is acknowledged. The submission is in compliance with the provisions of 37 CFR §1.97. Accordingly, the Examiner has considered the information disclosure statement, and a signed copy is enclosed herewith.
Applicant’s IDS filed April 19, 2024 (8 pages) is acknowledged. The submission is in compliance with the provisions of 37 CFR §1.97. Accordingly, the Examiner has considered the information disclosure statement, and a signed copy is enclosed herewith.
Applicant’s IDS filed April 19, 2024 (11 pages) is acknowledged. The submission is in compliance with the provisions of 37 CFR §1.97. Accordingly, the Examiner has considered the information disclosure statement, and a signed copy is enclosed herewith.
The listing of references in the specification at pages 34-36 is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Drawings
The Drawings filed on July 11, 2023 are acknowledged. However, the Drawings are objected to because some Drawings reference the colors "red" and "blue". See Figures 1 and 4, for example. In the instant application, color drawings have been filed without an accompanying petition. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Color photographs and color drawings are not accepted unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), three sets of color drawings or color photographs, as appropriate, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37CFR 1.84(b)(2). Note that the requirement for three sets of color drawings under 37 CFR 1.84(a)(2)(ii) is not applicable to color drawings submitted via EFS-Web. Therefore, only one set of such color drawings is necessary when filing via EFS-Web.
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.
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.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) 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.
Claims 1, 2, 5, 12, 20, 24, 27, 39, 41, 42, 44, 46, 47, 49, 51, 54, 56-58, 61 and 76 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2018/232357 A1 (to MODERNATX) 20 December 2018 (submitted on the IDS filed May 21, 2026 (37 pages)) in view of Banga et al. (J. Am. Chem. Soc. 2014 Vol. 136:9866-9869) ((submitted on the IDS filed May 21, 2026 (37 pages)) and further in view of U.S. Patent No. 6,465,188.
The claims are drawn to a lipid nanoparticle spherical nucleic acid (LNP-SNA) comprising a lipid nanoparticle core and a shell of oligonucleotides comprised of oligonucleotides attached to the exterior of the lipid nanoparticle core, the lipid nanoparticle core comprising an encapsulated oligonucleotide, an ionizable lipid, a phospholipid, a sterol, and a lipid-polyethylene glycol (lipid-PEG) conjugate, wherein an oligonucleotide in the shell of oligonucleotides is covalently attached to the exterior of the lipid nanoparticle core through the lipid-PEG conjugate.
Regarding claims 1 and 61, MODERNATX teach an ionizable-lipid lipid nanoparticle having a lipid outer shell and an inner core within which RNA is encapsulated. For example, MODERNATX teach a composition comprising an enriched population of lipid nanoparticles (LNPs), wherein the LNPs have an outer shell and an inner core and comprises an ionizable lipid, a phospholipid, a PEG lipid, and a structural lipid, wherein at least 50% of the LNPs comprise RNA encapsulated within the inner core and wherein the outer shell comprises at least 95% of the total PEG lipid in the LNP. LNPs comprise inaccessible mRNA; and accessible mRNA (no more than about 50% of mRNA in the composition). See claims. Also, see Example 5.
MODERNATX further teach that the lipid-PEG conjugate is surface-accessible (e.g. disposed at and/accessible from the exterior of the lipid nanoparticle core). Further, the nucleic acid of MODERNATX is “exposed to the exterior of the LNP”.
MODERNATX teach the nucleic acid of their invention is exposed to the exterior of the LNP, but does not necessarily teach that an oligonucleotide in the shell of oligonucleotides is covalently attached to the exterior of the lipid nanoparticle core through the lipid-PEG conjugate.
Regarding claims 1 and 61, Banga et al. teach a spherical nucleic acid comprising a lipid-based (liposomal) core, the exterior of which is functionalized with a shell of oligonucleotides oriented radially about the core. See Scheme 1. Banga et al. teach that the spherical nucleic acid stabilizes the liposomal construct and facilitates cellular internalization and gene regulation without the need for ancillary transfection reagents.
Regarding claims 2, 5, and 27, according to Banga et al. the shell of oligonucleotides or encapsulated oligonucleotide comprises about 5 to about 1000 oligonucleotides. See Banga et al. page, 9867, left column.
Regarding claim 76, Banga et al. teach at least 10% of the oligonucleotides in the shell of oligonucleotides are covalently attached to the lipid nanoparticle.
Regarding claim 12, the shell of the oligonucleotides is comprised of single-stranded DNA oligonucleotides, double- stranded DNA oligonucleotides, single-stranded RNA oligonucleotides, double-stranded RNA oligonucleotides, or a combination thereof. See MODERNATX, claim 1, for example. Also, see Banga et al. Scheme 1.
Regarding claims 20 and 24, MODERNATX and Banga et al. both teach the shell of oligonucleotides or encapsulated oligonucleotide comprises an inhibitory oligonucleotide, an immunostimulatory oligonucleotide, a gene editor substrate DNA or RNA or a combination thereof.
Regarding claims 1 and 61, U.S. Patent No. 6,465,188 teach covalently attaching an oligonucleotide to the exterior of a lipid vesicle through a PEG conjugate. For example, U.S. Patent No. 6,465,188 teaches conjugating a thio-modified oligonucleotide to a DSPE-PEG-2000 bearing a reactive maleimide, thereby covalently linking the oligonucleotide to the lipid-PEG-conjugate. See Example 14.
Regarding claims 39, 42, 46, 49 and 51 MODERNATX teach the ionizable lipid is DLin-KC2-DMA; the phospholipid is DPPC; the sterol is cholesterol or a cholesterol derivative such as ergosterol; and the lipid PEG comprises 2000 Dalton PEG.
Regarding claims 41, 44, 47 and 54, MODERNATX teach the LNP-nucleic acid of their invention comprises a molar fraction of the ionizable lipid that is about 50% of the total lipid in the LNP-nucleic acid; the LNP-nucleic acid of their invention comprises a molar fraction of the phospholipid that is about 1% to about 25% of the total lipid in the LNP-nucleic acid; the LNP-nucleic acid of their invention comprises a molar fraction of the sterol that is about 25% to about 45% of the total lipid in the LNP-nucleic acid; and the LNP-nucleic of their invention comprises a molar fraction of the lipid-PEG conjugate that is about 1.5% to about 3.5% of the total lipid in the LNP-nucleic acid.
Regarding claim 56, MODERNATX teach the mass ratio between the ionizable lipid and the encapsulated oligonucleotide is about 20:1 to about 5:1.
Regarding claims 57 and 58, according to MODERNATX, the lipid LNP-nucleic acid of their invention further comprises a therapeutic agent encapsulated in the lipid nanoparticle core.
Before the effective filing date of the claimed invention, it would have been prima facie obvious to a person of ordinary skill in the art to modify the lipid nanoparticle of MODERNATX by providing a shell of oligonucleotides covalently attached to the exterior of the lipid nanoparticle core through the surface-accessible lipid-PEG conjugate, as taught and suggested by Banga et al. and U.S. Patent No. 6,465,188, thereby arriving at the claimed invention.
A person of ordinary skill in the art would have been motivated to make this modification since Banga et al. teach that arranging oligonucleotides as a radial shell on the exterior of a lipid core (the spherical nucleic acid) confers stability upon the construct and facilitates cellular internalization and gene regulation benefits.
The skilled artisan seeking to improve the cellular uptake and stability of the MODERNATX lipid nanoparticle would have looked to Banga et al. spherical nucleic acid to obtain these recognized benefits. Moreover, MODERNATX already provides the very structural feature required to carry out the attachment – teaching that its lipid-PEG conjugate is surface-accessible at the exterior of the core, thereby presenting the lipid-PEG terminus at which the shell oligonucleotide is to be attached.
The modification amounts to the combination of prior art elements according to known methods to yield predictable results, and to the use of a known technique (covalent conjugation of a modified oligonucleotide to an accessible, reactive and functional lipid-PEG terminus, as in U.S. Patent No. 6,465,188) to improve the surface-PEGylated lipid nanoparticle of MODERNATX. See KSR Int’l Co. v. Teleflex Inc. 550 U.S. 398, 416-417 (2007). Also, see MPEP 2143(A) and (C).
One of ordinary skill in the art would have had a reasonable expectation of success since thiol-maleimide conjugation of oligonucleotides to DSPE-PEG was an established and well-known and characterized technique as evidenced by U.S. Patent No. 6,465,188.
Therefore, the subject matter of claims 1, 2, 5, 12, 20, 24, 27, 39, 41, 42, 44, 46, 47, 49, 51, 54, 56-58, 61 and 76 is obvious over MODERNATX in view of Banga et al. and further in view of U.S. Patent No. 6,465,188.
Conclusion
No claims are allowable at this time.
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Terra C. Gibbs whose telephone number is 571-272-0758. The Examiner can normally be reached from 8 am - 5 pm M-F.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner's supervisor, Ram Shukla can be reached on 571-272-0735. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/TERRA C GIBBS/Primary Examiner, Art Unit 1635
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