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 .
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The listing of references in the specification 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.
Election/Restrictions
Applicant's election with traverse of Group I drawn to a polymeric nanoparticle formulation in the reply filed on 20 April 2026 is acknowledged. The traversal is on the grounds that search for the polymeric nanoparticle of Group I would necessarily overlap with the search of non-elected Group II as the method of group II requires the formulation of Group I. This is not found persuasive because establishment of a search burden is not a requirement for restriction of an application filed under 35 U.S.C. 371. As such, arguments concerning burden of examination are not sufficient to overcome the restriction requirement.
The requirement is still deemed proper and is therefore made FINAL.
Claims 11-12 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 20 April 2026.
Applicant’s election without traverse of a species of divinyl monomer bearing an aromatic ring of (2-nitro-1,3-phenylene)bis(methylene) diacrylate; a species of piperazine divinyl monomer of 1,4-bis(acryloyl)piperazine; a species of amino alcohol monomer of 6-amino-1-hexanol; and a species of polymer having a 50% divinyl monomer : 50% amine alcohol mole ratio in the reply filed on 20 April 2026 is acknowledged.
Claims 1-10 are examined on the merits herein.
Claim Rejections - 35 USC § 102
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.
Claims 1-10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Francisco et al. (Methods, 31 December 2020, Vol. 190, 13-25 cited on Applicant’s IDS filed 8 March 2024).
Claim 1 is drawn to a polymeric nanoparticle formulation for targeted delivery of mRNA to cells comprising a polymer made of divinyl monomers bearing an aromatic ring, piperazine containing divinyl monomers, and amino alcohol monomers, wherein the polymer is complexed with mRNA to form the nanoparticles.
Claim 2 is drawn to the formulation of claim 1, wherein the divinyl monomer bearing an aromatic ring is (2-nitro-1,3-phenylene)bis(methylene) diacrylate (Applicant’s elected species).
Claim 3 is drawn to the formulation of claim 1, wherein the piperazine divinyl monomer is 1,4-bis(acryloyl)piperazine (Applicant’s elected species).
Claim 4 is drawn to the formulation of claim 1, wherein the amino alcohol monomer is 6-amino-1-hexanol.
Francisco et al. teach polymeric nanoparticles for the delivery of mRNA (Abstract). Francisco et al. further teach nanoparticles comprising the polymer P1E28 complexed with mRNA (Fig. 5, pg. 19 left column last paragraph), wherein P1E28 comprises (2-nitro-1,3-phenylene)bis(methylene) diacrylate, 1,4-bis(acryloyl)piperazine, and 6-amino-1-hexanol (Table on pg. 24, Fig. 5B).
As such, claims 1-4 are anticipated.
Claim 5 is drawn to the formulation of claim 1, wherein the molar ratio per repeating unit of the polymer is 50% divinyl monomers:50% amino alcohol.
Francisco et al. further teach forming the polymer by combining 50µL of P1, 50µL of bisacrylamide monomer, and 100µL of the amine alcohol, wherein each monomer solution had a concentration of 1.6M (Pg. 14 left column last paragraph), corresponding to a molar ratio of 50% divinyl monomers : 50% amino alcohol.
As such, claim 5 is anticipated.
Claim 6 is drawn to the formulation of claim 1, wherein the molar ration per repeating unit of the polymer of any of the divinyl monomers varies between 5% and 45%.
Francisco et al. further teach forming the polymer by combining 50µL of P1, 50µL of bisacrylamide monomer, and 100µL of the amine alcohol, wherein each monomer solution had a concentration of 1.6M (Pg. 14 left column last paragraph), corresponding to a molar ratio for each divinyl monomer of 25%.
As such, claim 6 is anticipated.
Claim 7 is drawn to the formulation of claim 1, wherein the mass ratio of mRNA to polymer is between 1:5 and 1:200.
Claim 8 is drawn to the formulation of claim 1, wherein the mass ratio of mRNA: polymer is 1:100.
Francisco et al. further teach mass ratios of mRNA to polymer of 1:0.1 to 1:100 (Fig 5C), overlapping with the instantly claimed range.
As such, claims 7-8 is anticipated.
Claim 9 is drawn to the formulation of claim 1, wherein the nanoparticles have an average size between 200 and 600 nm.
Francisco et al. further teach the nanoparticles having an average size of 405±242 nm (pg. 17 right column second paragraph), overlapping with the instantly claimed range.
As such, claim 9 is anticipated.
Claim 10 is drawn to the formulation of claim 1, wherein the nanoparticles have a zeta potential between +5 and +25 mV.
Francisco et al. further teach the nanoparticles having a zeta potential of +12.7±8.6 mV (pg. 17 right column second paragraph), overlapping with the instantly claimed range.
As such, claim 10 is anticipated.
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.
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 1-10 are rejected under 35 U.S.C. 103 as being unpatentable over Blersch et al. (Angew. Chem. Int. Ed., 20 December 2019, Vol. 59, 1985-1991 cited on Applicant’s IDS filed 8 March 2024) in view of Islam et al. (Biomater Sci, 2015, Vol. 3, 1519-1533).
Claim 1 is drawn to a polymeric nanoparticle formulation for targeted delivery of mRNA to cells comprising a polymer made of divinyl monomers bearing an aromatic ring, piperazine containing divinyl monomers, and amino alcohol monomers, wherein the polymer is complexed with mRNA to form the nanoparticles.
Claim 2 is drawn to the formulation of claim 1, wherein the divinyl monomer bearing an aromatic ring is (2-nitro-1,3-phenylene)bis(methylene) diacrylate (Applicant’s elected species).
Claim 3 is drawn to the formulation of claim 1, wherein the piperazine divinyl monomer is 1,4-bis(acryloyl)piperazine (Applicant’s elected species).
Claim 4 is drawn to the formulation of claim 1, wherein the amino alcohol monomer is 6-amino-1-hexanol.
Blersch et al. teach polymeric nanoparticle formulations for the delivery of RNA (Abstract), further teaching nanoparticles formed of the polymer P1E28 comprising (2-nitro-1,3-phenylene)bis(methylene) diacrylate, 1,4-bis(acryloyl)piperazine, and 6-amino-1-hexanol (Fig. 1B; “Synthesis of polymers with photocleavable moieties” on pgs. 2-3 of the SI). Blersch et al. further teach complexing the nanoparticles with siRNA (“High-throughput complexation of NPs with siRNAs” on pgs. 4-5 of the SI).
Blersch et al. do not teach the RNA being mRNA.
Islam et al. teach biomaterials for mRNA delivery (Title) including polymeric nanoparticles (pgs. 7-9), further teaching mRNA as a safe genetic material for gene-based therapy as well as having predictable, consistent protein expression kinetics (Pg. 1 first paragraph). Islam et al. further teach many delivery strategies for siRNA exhibiting a promising foundation for mRNA delivery technologies (Pgs. 1-2 bridging paragraph) and polymeric nanoparticles showing great potential for mRNA delivery (Pg. 9 first paragraph) with multiple examples of polymeric nanoparticle delivery systems presented in Table 2 (Pg. 23).
Therefore, it would have been prima facie obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have modified the composition of Blersch et al. to comprise mRNA as taught by Islam et al. It would have been obvious to combine the known polymeric nanoparticle for the delivery of RNA with the known delivery of mRNA via polymeric nanoparticles for gene-based therapy to yield the predictable result of an mRNA delivery system for gene-based therapy with consistent protein expression kinetics, with a reasonable expectation of success.
Based on all of the foregoing, claims 1-4 are rejected as prima facie obvious.
Claim 5 is drawn to the formulation of claim 1, wherein the molar ratio per repeating unit of the polymer is 50% divinyl monomers:50% amino alcohol.
Claim 6 is drawn to the formulation of claim 1, wherein the molar ration per repeating unit of the polymer of any of the divinyl monomers varies between 5% and 45%.
Blersch et al. further teach the polymer being synthesized from 25µL of P1, 25µL of bisacrylamide monomer, and 50µL of the amine alcohol, wherein each monomer solution had a concentration of 1.6 M (“Synthesis of polymers with photocleavable moieties” on pgs. 2-3 of the SI), corresponding to a 50% divinyl monomer:50% amino alcohol molar ratio, with each of the divinyl monomers having a 25% molar ratio, overlapping with the instantly claimed range.
As such, claims 5-6 are rejected as prima facie obvious.
Claim 7 is drawn to the formulation of claim 1, wherein the mass ratio of mRNA to polymer is between 1:5 and 1:200.
Blersch et al. further teach the mass ratio of RNA to the polymer between 1:12.5 and 1:50 (SI pg. 2 first paragraph), overlapping with the instantly claimed range.
As such, claim 7 is rejected as prima facie obvious.
Claim 8 is drawn to the formulation of claim 1, wherein the mass ratio of mRNA: polymer is 1:100.
Blersch et al. do not teach a mass ratio of RNA to polymer of 1:100.
However, Blersch et al. teach optimization of the ratio of RNA:polymer (SI pg. 2), further teaching the ratio having a direct impact on the bioefficacy of the nanoparticle (Fig. S5B), indicating the ratio of RNA:polymer as a result-effective variable.
And, as discussed by MPEP 2144.05, “[g]enerally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical” (see also In re Aller (220 F.2d 454)): “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation…” Indeed, as further discussed by the court, “[s]uch experimentation is no more than the application of the expected skill of the [ordinarily skilled artisan] and failure to perform such experiments would, in our opinion, show a want of the expected skill”; see also In re Peterson, 315 F.3d at 1325 (Fed. Cir. 2005): “[t]he normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages” and “[o]nly if the ‘results of optimizing a variable’ are ‘unexpectedly good’ can a patent be obtained for the claimed critical range” (quoting In re Antonie (559 F.2d 618 (CCPA 1977))).
In the instant case, the mass ratio of mRNA:polymer is clearly a result-effective variable, determining the bioefficacy of the nanoparticles. Accordingly, it would have been customary for an artisan of ordinary skill in the art to determine the optimal mass ratio of mRNA:polymer in order to best achieve the desired results.
As such, claim 8 is rejected as prima facie obvious.
Claim 9 is drawn to the formulation of claim 1, wherein the nanoparticles have an average size between 200 and 600 nm.
Blersch et al. further teach 90% of the nanoparticles having a size range between 100 and 500 nm (Pg. 1986 left column third paragraph), overlapping with the instantly claimed range.
As such, claim 9 is rejected as prima facie obvious.
Claim 10 is drawn to the formulation of claim 1, wherein the nanoparticles have a zeta potential between +5 and +25 mV.
Blersch et al. further teach in Fig. S3E the P1E28 nanoparticles having a zeta potential of about +20 mV, overlapping with the instantly claimed range.
As such, claim 10 is rejected as prima facie obvious.
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 1-10 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 6-8, and 11 of copending Application No. 17/611,278 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
Claim 1 of Application No. ‘278 recites a nanoparticle library of formulations for controlled release of RNA wherein the formulations comprise: polymeric nanoparticles comprising photocleavable linker monomers; amine monomers; and bisacrylamide monomers; wherein the nanoparticles are complexed with RNA, rendering instant claim 1 obvious.
Claim 2 of Application No. ‘278 recites the formulation of claim 1, wherein the photocleavable linker is (2-nitro-1,3-phenylene)bis(methylene) diacrylate, rendering instant claim 2 obvious.
Claim 3 of Application No. ‘278 recites the formulation of claim 1, wherein the bisacrylamide monomer is bisacryloylpiperazine, rendering instant claim 3 obvious.
Claim 4 of Application No. ‘278 recites the formulation of claim 1, wherein the amine monomer is selected from a group including 3-amino-1-propanol, 4-amino-1-butanol, 5-amino-1-pentanol, and 6-amino-1-hexanol, rendering instant claim 4 obvious.
Claim 6 of Application No. ‘278 recites the formulation of claim 2, wherein the molar ratio of the polymer is 25(P1):25(bisacrylamide):50(amine), rendering instant claims 5-6 obvious.
Claim 7 of Application No. ‘278 recites the formulation of claim 1, wherein 90% of the nanoparticles have a size range between 100 and 500 nm, rendering instant claim 9 obvious.
Claim 8 of Application No. ‘278 recites the formulation of claim 1, wherein 20% of the nanoparticles have a zeta potential above 20 mV, rendering instant claim 10 obvious.
Claim 11 of Application No. ‘278 recites the formulation of claim 1, wherein the weight ratio of mRNA:NP varies between 1:5 and 1:100, rendering instant claims 7-8 obvious.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Paul Hoerner whose telephone number is (571)270-0259. The examiner can normally be reached Monday - Friday 9:00am - 5:00pm eastern.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bethany Barham can be reached at (571)272-6175. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/PAUL HOERNER/Examiner, Art Unit 1611
/CRAIG D RICCI/Primary Examiner, Art Unit 1611
Prosecution Insights