DETAILED ACTION
Applicants’ arguments, filed 26 January 2026, have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Interpretation
Claim 1 has been amended to require that the PEG-b-PLA nanoparticle is coated with a cationic polymer. The claim has been amended such that “coated” has replaced “formulated.”
As best understood by the examiner, the amendment to recite the term “coated” excludes a particle wherein the cationic polymer is in the interior of the particle. Also, as best understood by the examiner, the claim amendment excludes a particle where the cationic polymer is covalently bound to the PEG-b-PLA. This is because in such a situation, the polymer would actually be (cationic polymer)-b-PEG-b-PLA or PEG-b-PLA-b-(cationic polymer), not PEG-b-PLA.
As such, the scope of claim 1 appears to include the following case; namely, the case in which the cationic polymer is not covalently bound to the PEG-b-PLA and the cationic polymer is on the exterior of the particle.
The examiner notes that the examples in the specification all appear to be drawn to cases in which the cationic polymer is not covalently bound to the PEG-b-PLA. This further supports the examiner’s position that the claim should be interpreted as not including the case wherein the cationic polymer is covalently bound to the PEG-b-PLA.
Withdrawn Prior Art Rejections
Previously in the prosecution history, the examiner rejected the instant claims as being anticipated by and/or obvious over Merlin et al. (US 2015/0147270 A1) and Saltzman et al. (US 2019/0133962 A1). Both references teach PEG-b-PLA, as well as polyethyleneimine, which is abbreviated as “PEI” and is a cationic polymer. However, the examiner agrees with applicant’s arguments that both references fail to teach that the PEI coats the PEG-b-PLA. See the following text from page 7 of applicant’s response.
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See also the following text from page 8 of applicant’s response, reproduced below.
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The examiner agrees with these arguments and has withdrawn the previously applied rejections. There would have been no motivation for the skilled artisan to have modified Merlin or Saltzman to have had coated the PEG-b-PLA particle of Merlin/Saltzman with PEI rather than to have loaded the PEG-b-PLA particle of Merlin/Saltzman with PEI. This is at least because PEI is being used by the prior art to electrostatically bind an active agent, which is siRNA in Merlin, paragraph 0092 and NGI-1 in Saltzman. Encapsulating the PEI/active agent complex in the nanoparticle appears to have helped protect the PEI and active agent from degradation in the body prior to release at the desired location in the prior art, and the skilled artisan would not have been motivated to have modified the prior art to have placed the PEI on the outside the particle and to thereby have removed the above-discussed protection afforded by the PEG-b-PLA.
Furthermore, there would have been no reasonable expectation that Merlin and/or Saltzman could have been successfully modified to have coated the PEG-b-PLA particle of the prior art with PEI rather than loaded the PEG-b-PLA particle of the prior art with PEI. This is at least because neither Merlin nor Saltzman teach an anionic moiety on the outside of the PEG of the PEG-b-PLA that would engage in electrostatic bonding with the positive charge of the PEI.
Relevant Prior Art – No Rejection
As relevant prior art over which the examiner has not rejected the claims, the examiner cites Sukumar et al. (ACS Applied Materials and Interfaces, Vol. 12, 2020, pages 11307-11319 and S1-S35). Sukumar et al. (hereafter referred to as Sukumar) is drawn to a triblock copolymer nanoparticle, as of Sukumar, page 11307, title, abstract, and figure in abstract, reproduced in part below.
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As an initial matter, Sukumar differs from the claimed invention because Sukumar teaches poly(D,L-lactic-co-glycolic acid) (PLGA) whereas the instant claims require polylactic acid (PLA). Nevertheless, even if, purely en arguendo, it would have been prima facie obvious for the skilled artisan to have substituted PLA in place of PLGA, the resultant composition still would not have anticipated or rendered obvious the instantly claimed invention. This is because Sukumar teaches a copolymer of PLGA-PEG-PEI where the PEI (i.e. polyethyleneimine) is covalently bound to the PEG; see e.g. Sukumar, page S10, relevant text reproduced below.
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The above-reproduced text teaches PLGA-PEG-PEI. Even if, purely en arguendo, the skilled artisan was to have substituted PLA in place of PLGA, the resultant polymer would have been PLA-PEG-PEI, with the PEI conjugated to the PEI by covalent bonding. This would not have rendered the claimed invention obvious because PLA-PEG-PEI is not the same as PEG-b-PLA, and covalent conjugation is not the same as coating.
The examiner also notes that the polymer PEI-b-PLA-b-PEG is known in the art, as of Sim et al. (Journal of Bioactive and Compatible Polymers, Vol. 32(3), 2017, pages 280-292), which teaches this polymer as of page 280, title and abstract, as well as page 282, figure 1, reproduced below.
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Nevertheless, this does not read on the instantly claimed invention. This is because PEG-b-PLA-PEI is not the same as PEG-b-PLA and covalent conjugation is not the same as coating.
Claim Rejections - 35 USC § 112(a) – Written Description
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 1-19 and 24 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.
Claim 1 has been amended in the following manner:
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It is the examiner’s position that the newly added term “coated” does not appear to be adequately supported by the original application as filed. The examiner presents the following rationale in support of this position.
The instant specification discloses the following on page 25, relevant text reproduced below.
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The phrase “PLA-PEG/PEI” refers to PEI-coated PLA-PEG; see the instant specification on page 3, paragraph 0008, relevant text reproduced below.
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The examiner also notes that the PLA-PEG in Example 1 of the instant specification appears to be methoxy-terminated on both the PLA end and the PEG end, as of instant figure 1, reproduced in part below.
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A description as filed is presumed to be adequate, unless or until sufficient evidence or reasoning to the contrary has been presented by the examiner to rebut the presumption. The examiner, therefore, must have a reasonable basis to challenge the adequacy of the written description. The examiner has the initial burden of presenting by a preponderance of evidence why a person skilled in the art would not recognize in an applicant’s disclosure a description of the invention defined by the claims. In rejecting a claim, the examiner must set forth express findings of fact regarding the above analysis which support the lack of written description conclusion. These findings should:
(A) Identify the claim limitation at issue; and
(B) Establish a prima facie case by providing reasons why a person skilled in the art at the time the application was filed would not have recognized that the inventor was in possession of the invention as claimed in view of the disclosure of the application as filed. A general allegation of "unpredictability in the art" is not a sufficient reason to support a rejection for lack of adequate written description. See MPEP 2163(III)(A) and MPEP 2163.04.
In this case, the claim limitation at issue relates to the newly introduced term “coated” on the third line of claim 1, which is understood by the examiner to refer to a non-covalent coating. It is the examiner’s position that, contrary to the position taken in the specification, the skilled artisan would not have expected that incubating PEI (a cationic polymer) with PEG-b-PLA, which was done in the examples, would have resulted in PEI coating said PEG-b-PLA particles. In contrast, the skilled artisan would have expected that incubating PEI with PEG-b-PLA would have resulted in PEG-b-PLA particles being suspended in a solvent, with the cationic polymer dissolved in said solvent but not in contact with or attached to the PEG-b-PLA particles. The examiner presents the following rationale in support of this position.
PEI is a cationic polymer comprising multiple repeating amino groups. See Jiang et al. (Topics in Current Chemistry Collections, Vol. Z, 2017, 375:34, pages 1-36), which is drawn to polyethyleneimine-based gene carriers, as of Jiang et al. (hereafter referred to as Jiang), title and abstract. Specifically, Jiang teaches polyethyleneimine as having the following structure, as of Jiang, page 5, figure 2, reproduced below.
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Low molecular weight PEI would have had a pKa in the 8-9 range, as of Mady et al. (Romanian Journal of Biophysics, Vol. 21 No. 2, 2011, pages 151-165), specifically as of page 158, Table 1, reproduced below.
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As such, the skilled artisan would have expected polyethyleneimine to have comprised multiple positively charged groups at neutral pH.
Because of the positive charge of polyethyleneimine, the skilled artisan would have expected the primary form of intermolecular interaction of polyethyleneimine to have been ion-ion interactions, in which the positive charge of polyethyleneimine engages in charge-charge attraction with a negative charge. As such, the skilled artisan would have expected a cationic polymer such as PEI to have been able to have coated a particle with a negative charge at the surface due to said ion-ion intermolecular interactions between cationic PEI and the anionic particle. However, the skilled artisan would not have expected PEI to have coated a particle without a negative charge at the surface as said ion-ion intermolecular interactions would not have been able to have formed.
The examiner conducted a search regarding polyethyleneimine (PEI) coating of any type of particle. As a result of such a search, the examiner cites Ge et al. (ACS Applied Materials & Interfaces, Vol. 7, 2015, pages 6102-6108 and S1-S16). Ge et al. (hereafter referred to as Ge) teaches PEI coated magnetic nanoparticles, as of Ge, page 6102, title and abstract. Ge teaches that uncoated magnetic nanoparticles (abbreviated as MNPs) carry a negative charge, as of Ge, page 6104, right column, last paragraph. This negative charge appears to be what causes the positively charged PEI to be able to coat the negatively charged magnetic nanoparticles.
The PEG-b-PLA disclosed by the instant application, in contrast to the particles of Ge, appears to lack negative charges on the uncoated particle. As such, ion-ion interactions would not appear to be present between the polyethylenimine (PEI) and the PEG-b-PLA. Therefore, polyethyleneimine would not have been expected to have stayed on the surface of the PEG-b-PLA nanoparticle due to the lack of charge attraction experienced during ion-ion interactions. The skilled artisan would therefore have expected that mixing polyethyleneimine and PEG-b-PLA would have resulted in the polyethyleneimine being present in solution with the PEG-b-PLA, but would not have resulted in the polyethyleneimine coating the PEG-b-PLA.
In view of this, the examiner takes the position that applicant has not adequately described a nanoparticle comprising a cationic polymer coated PEG-b-PLA.
The examiner notes that if applicant amends the claims to overcome this rejection, the examiner may reconsider the decision not to reject the instant claims as anticipated by or obvious over prior art rejections. As such, a claim amendment made by applicant could potentially result in the examiner issuing a new prior art rejection.
Non-Statutory 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 1-19 and 24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-28 of copending Application No. 17/284,262 in view of Farokhzad et al. (WO 2018/112470 A1).
Instant claim 1 is drawn to a nanoparticle comprising a PEG-b-PLA coated with a cationic polymer, and a nanoparticle. The claims recite a specific molecular weight of the PLA and PEG. Instant claim 3 recites a nucleic acid therapeutic.
Copending claim 1 is drawn to a nanoparticle comprising PLGA-PEG coated with a cationic polymer as well as a nucleic acid therapeutic agent. Copending claims 27-28 recite specific molecular weights of the PEG and PLGA.
The copending claims differ from the instant claims because the copending claims recite PLGA-PEG (i.e. PEG-b-PLGA), whereas the instant claims require PEG-b-PLA. PLGA refers to poly(lactic-co-glycolic acid) whereas PLA refers to polylactic acid.
Farokhzad et al. (hereafter referred to as Farokhzad) is drawn to delivery of nucleic acids, as of Farokhzad, title and abstract. Farokhzad utilizes a nanoparticle to deliver said nucleic acids, which may comprise either PLGA-PEG or PLA-PEG, as of Farokhzad, page 14, bottom paragraph, relevant text reproduced below.
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It would have been prima facie obvious for one of ordinary skill in the art to have substituted the PLA-PEG of Farokhzad in place of the PLA-PEG of the copending claims. The copending claims are drawn to PLGA-PEG for nucleic acid delivery. Farokhzad teaches that PLGA-PEG and PLA-PEG can be used as alternatives for nucleic acid delivery. As such, the skilled artisan would have been motivated to have substituted the PLA-PEG of Farokhzad in place of the PLGA-PEG of the copending claims for predictable delivery of the nucleic acid active agent in the copending claims with a reasonable expectation of success. The simple substitution of one element (PLA-PEG, as of Farokhzad) in place of another (PLA-PEG, as required by the instant claims) in order to achieve predictable results (nucleic acid delivery) is prima facie obvious. See MPEP 2143, Exemplary Rationale B.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
The previously applied objection for failing to include required information relating to nucleotide and/or amino acid sequences has been withdrawn in view of applicant’s submission on 26 January 2026.
The previously applied indefiniteness rejections and objections have been withdrawn in view of the claim amendments.
The previously applied prior art rejections have been withdrawn in view of the claim amendments and the cancellation of claim 20. See the section above entitled “Withdrawn Prior Art Rejections.”
The examiner previously rejected claim 20 on the ground of non-statutory double patenting over the claims of copending application 17/284,262. This rejection has been withdrawn in view of the cancellation of claim 20.
As such, the only rejection that was applied in the prior office action that is being maintained is the double patenting rejection over claims of copending application 17/284,262 in view of Farokhzad et al. (WO 2018/112470 A1). Applicant addressed this in applicant’s response on 26 January 2026 (hereafter referred to as applicant’s response) on page 11, where the relevant text is reproduced below.
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This is not persuasive. These arguments primarily relate to deficiencies in the teachings of Farokhzad. The examiner does not dispute that there are differences between Farokhzad and the claimed invention, and it is for this reason that the claims were not rejected as anticipated by Farokhzad or obvious over Farokhzad by itself. The examiner cited Farokhzad to support the idea that the skilled artisan would have been motivated to have substituted PLA-PEG in place of PLGA-PEG, at least because Farokhzad teaches these as alternatives. Applicant’s arguments regarding alleged deficiencies of Farokhzad appears to address Farokhzad by itself rather than the combination of references. One cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See MPEP 2145(IV).
Relevant Art – No Rejection Due to AIA Exception
As relevant art, the examiner cites Zhao (WO 2020/077178 A1). Zhao et al. (hereafter referred to as Zhao) is drawn to PLGA-PEG, PEI, and nucleic acid containing nanoparticles, as of Zhao, title and abstract. The is the same subject matter as the claimed invention.
Zhao was published on 16 April 2020. This is less than a year earlier than the effective filing date of the claimed invention, which is 23 February 2021 (based upon the filing date of provisional application 63/152,185). Zhao was also effectively filed earlier than the effective filing date of the instant application. Nevertheless, Zhao (WO 2020/077178 A1) has the same inventive entity as the instant application. As such, the exceptions under both AIA 35 U.S.C. 102(b)(1)(A) and 35 U.S.C. 102(b)(2)(A) would appear to be applicable; see at least MPEP 2154.01(c). As such, no rejection over Zhao (WO 2020/077178 A1) has been written by the examiner.
The examiner also notes Zhao (US 2021/0388393 A1), which was effectively filed earlier than the effective filing date of the instant application. Nevertheless, this reference is not prior art under the AIA 35 U.S.C. 102(b)(2)(A) exception for essentially the same reason that Zhao (WO 2020/077178 A1) is not prior art under the AIA 35 U.S.C. 102(b)(2)(A) exception.
Conclusion
No claim is allowed.
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 ISAAC SHOMER whose telephone number is (571)270-7671. The examiner can normally be reached 7:30 AM to 5:00 PM Monday Through Friday.
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ISAAC . SHOMER
Primary Examiner
Art Unit 1612
/ISAAC SHOMER/ Primary Examiner, Art Unit 1612