DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after 16 March 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Election/Restriction
Applicant’s election without traverse of Group I, claims 1-2, 6, 10-11, 15-18, 20-25, 27-32, and 60, and the species B7-S90, Sc12-E63, 50%/50% ratio of S90/Sc12, a self-amplifying mRNA (SAM) that encodes a rabies virus glycoprotein, 1,2-dimyristoryl-rac-glycero-3-methoxypolyethylene glycol 2000 (DMG-PEG2k), MgCl2, and rabies in the reply filed on 13 May 2026, is acknowledged.
NOTE: 1,2-dimyristoryl-rac-glycero-3-methoxypolyethylene is interpreted as being 1,2-dimyristoyl-rac-glycero-3-methoxypolyethyle as recited in instant claim 18.
Status of Claims
The preliminary amendment, filed on 13 May 2026, is acknowledged.
Claim 15 has been amended.
Claims 1-2, 6, 10-11, 15-18, 20-25, 27-32, 37-41, 47-50, and 57-60 are pending in the instant Office Action.
Claims 37-41, 47-50, and 57-59 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 13 May 2026.
Claim 32 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Specifically, Applicant elected the one or more excipients recited in instant claim 31 to be MgCl2. Claim 32 further limits the one or more cryoprotectants, one or more sugars, and/or one or more sugar alcohols, which were not elected. Election was made without traverse in the reply filed on 13 May 2026.
Claims 1-2, 6, 10-11, 15-18, 20-25, 27-31, and 60 are under consideration in the instant Office Action, to the extent of the following elected species:
the specific compound of formula (I) is B7-S90, Sc12-E63, 50%/50% ratio of S90/Sc12;
the specific one or more nucleic acids is a self-amplifying mRNA (SAM) that encodes a rabies virus glycoprotein;
the specific one or more additional compounds in the nanoparticle is the lipid-polyethylene glycol (PEG) 1,2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol 2000 (DMG-PEG2k);
the specific at least three components are B7-S90, Sc12-E63, 50%/50% ratio of S90/Sc12, DMG-PEG2k, and the SAM that encodes a rabies virus glycoprotein;
the specific one or more excipients is MgCl2;
the specific disease is rabies; and
the specific contents of the kit are B7-S90, Sc12-E63, 50%/50% ratio of S90/Sc12, DMG-PEG2k, and the SAM that encodes a rabies virus glycoprotein.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 7 May 2024, was filed in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
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 16 and 22 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.
Claim 16 recites “greater than 50% of the dry particle mass” in line 2. There is insufficient antecedent basis for this limitation in the claim because neither claim 16 nor claim 1, from which claim 16 depends, recite “dry particle mass”. If Applicant intended for the compound of formula (I) to comprise >50% w/w of the entire nanoparticle or the total amount of the compound of formula (I) and the one or more nucleic acids, Applicant should amend claim 16 to replace “the dry particle mass” with one of the above phrases.
Claim 22 recites the nanoparticle of claim 1 “comprising a plurality of nanoparticles”. There is a contradiction regarding a singular nanoparticle comprising multiple nanoparticles, which does not have support in the original disclosure, rendering the claim indefinite.
NOTE: For the purpose of examination, the limitation regarding polydispersity in claim 22 is interpreted as applying to a plurality of nanoparticles according to claim 1.
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 for establishing a background for determining obviousness under 35 U.S.C. 103 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, 6, 10-11, 15-18, 20-23, 25, 27-29, and 60 are rejected under 35 U.S.C. 103 as being unpatentable over Rui (Dissertation, Johns Hopkins University, June 2021, provided by Applicant in the IDS filed on 7 May 2024) in view of Lou et al. (J. Control. Rel. 2020, 325, 370., provided by Applicant in the IDS filed on 7 May 2024, hereafter referred to as Lou).
Rui teaches the formation of nanoparticles from biodegradable poly(beta-amino ester) (PBAE) polymers to deliver mRNA (pg. 253-254, Abstract). Gene therapy with mRNA, including next generation vaccines, is taught to have spurred a great amount of research, but delivery of mRNA is taught to be difficult due to the molecule being membrane-impermeable (pg. 254, Introduction, para. 1). Delivery via nanoparticles (NPs) is taught to be a viable delivery method due to their ability to “overcome intracellular barriers” via rational design (pg. 254, Introduction, para. 2). In one embodiment, the PBAE-based NP taught by Rui is formed from the PBAE backbone with the formula in Figure 8-2A (reproduced below), which is equivalent to formula (I) in the instant claims, with R=B7, R”=S90, and R’’’=E63 and 50% Sc12 monomer, resulting in the elected species B7-S90, Sc12-E63, 50%/50% S90/Sc12 (pg. 258, Effects of PBAE Backbone Hydrophobicity and Figure 8-2). Rui further teaches that the NPs can be formed with nucleic acid “cargo”, the PBAE polymer comprising 60% w/w of the NP, and the NP to comprise 10% w/w DMG-PEG2k (Fig. 8-2, pg. 258, Effects of PBAE Backbone Hydrophobicity, and pg. 277, NP Formulation and Characterization).
PNG
media_image1.png
516
931
media_image1.png
Greyscale
Figure 8-2 reproduced from Rui
Rui does not teach the encapsulated nucleic acid to be a self-amplifying mRNA (SAM) that encodes a rabies virus glycoprotein, the nanoparticle to have a zeta-potential of -12 to +18 mV, nor the polydispersity of a composition comprising a plurality of nanoparticles. These deficiencies are offset by the teachings of Lou.
Lou teaches the delivery of SAM to develop potent vaccines via nanoparticles to “protect the SAM from degradation and achieve efficient delivery” (Abstract). Due to self-amplifying properties, Lou teaches that SAM are capable of eliciting “robust immunes responses with significantly lower doses as compared to conventional mRNA vaccines” (pg. 370, Introduction, para. 1). Due to their anionic and hydrophilic properties, Lou notes that cellular uptake of mRNA is impaired, requiring delivery via systems including nanoparticles (pg. 370-371, Introduction, para. 2). A number of SAM vaccines are taught be undergoing clinical trials, including treatment for disease caused by the rabies virus, and Lou teaches that the rabies virus glycoprotein (RVG) is “the only target for neutralizing antibodies” (pg. 371, left col., para. 1-3). Lou teaches the successful encapsulation of a SAM vaccine encoding RVG (RVG-SAM) and delivery to cells with all investigated NPs except for the NP comprising the cationic lipid 1,2-stearoyl-3-trimethylammonium-propane (DSTAP) (pg. 371, left col., para. 3, Table 1, Fig. 1, and Discussion). Investigating the physiochemical properties of the SAM-encapsulating NPs, Lou found that all of the NPs that efficiently encapsulated the RVG-SAM were monodisperse (polydispersity index (PDI) of 0.13-0.24) and exhibited a “neutral” zeta-potential (<5 mV), while the NPs formed with DSTAP had higher PDI (>0.4).
Guidelines on the obviousness of similar and overlapping ranges, amounts, and proportions are provided in MPEP § 2144.05. With respect to claimed ranges which “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). These guidelines apply to the amount of the compound of formula (I) and DMG-PEG2k in the nanoparticles, the zeta-potential, and the polydispersity of the nanoparticles. In each instance, the prior art taught values or ranges that fell within or significantly overlapped with the ranges recited in the instant claims.
It would have been prima facie obvious to a person of ordinary skill in the art, prior to the filing of the instant application, to combine the teachings of Rui and Lou to arrive at the invention of instant claims 1-2, 6, 10-11, 15-18, 20-23, 25, 27-29, and 60 because combining prior art elements according to known methods to enable new applications produces predictable results. Rui teaches NPs formed from the biodegradable PBAE polymer B7-S90, Sc12-E63, 50%/50% S90/Sc12 at 60% w/w and 10% w/w DMG-PEG2k which can encapsulate mRNA as “cargo” to act as a vaccine.
In view of the teachings of Lou, one of ordinary skill in the art would be motivated to select the RVG-SAM as the mRNA cargo because Lou teaches the nucleic acid to be capable of encoding RVG, the only target for neutralizing antibodies for rabies, and that they can be successfully and efficiently encapsulated in lipid NPs. The ordinary artisan would recognize the application of NP-encapsulated SAMs as vaccines in treating rabies and would be motivated to combine the RVG-SAM with the biodegradable NP made from B7-S90, Sc12-E63, 50%/50% S90/Sc12 and DMG-PEG2k. In addition, Lou teaches that lipid NPs that successfully and efficiently encapsulate RVG-SAM and deliver the mRNA vaccine to cells have polydispersity in the range of 0.13-0.24 and a zeta-potential of <5 mV. The ordinary artisan would desire their NPs to encapsulate and deliver the RVG-SAM successfully and would therefore be motivated to formulate their nanoparticles to have those physicochemical characteristics.
Rui and Lou are silent regarding a kit. However, the Applicant elected the specific contents of the kit to comprise the compound B7-S90, Sc12-E63, 50%/50% ratio of S90/Sc12, DMG-PEG2k, and the SAM that encodes a rabies virus glycoprotein. The teachings of Rui and Lou have rendered obvious a nanoparticle comprising the compound B7-S90, Sc12-E63, 50%/50% ratio of S90/Sc12, DMG-PEG2k, and RVG-SAM, therefore a kit comprising those three species is also obvious. As a result, there is a reasonable expectation of success in arriving at the invention of instant claims 1-2, 6, 10-11, 15-18, 20-23, 25, 27-29, and 60 in view of the teachings of Rui and Lou.
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
Claim 24 is rejected under 35 U.S.C. 103 as being unpatentable over Rui (Dissertation, Johns Hopkins University, June 2021, provided by Applicant in the IDS filed on 7 May 2024) in view of Lou (J. Control. Rel. 2020, 325, 370., provided by Applicant in the IDS filed on 7 May 2024) as applied to claims 1-2, 6, 10-11, 15-18, 20-23, 25, 27-29, and 60 above, and further in view of Green et al. (WIPO International Patent Publication No. WO 2020/077159 A1, published on 16 April 2020, provided by Applicant in the IDS filed on 7 May 2024, hereafter referred to as Green).
Rui and Lou have been described above and particularly relevant to claim 24 Rui teaches the PBAE polymer to nucleic acid ratio to be 60 w/w (pg. 277, NP Formulation and Characterization).
Rui and Lou do not teach the compound of formula (I) to be present in a ratio of 30:1 with the SAM (claim 24). These deficiencies are offset by the teachings of Green.
Green teaches biodegradable particles formed from PBAE for delivering plasmid DNA or a nucleic acid as well as compositions and kits comprising the particles (Title and Abstract). The nanoparticle is taught to be formed from a poly(beta-amino) ester polymer with substituents that in some embodiments are the biodegradable ester linkage B7, the hydrophilic S90, the alkyl chain Sc12, and an end-cap amine (claims 1, 9-10, 14, 17). The PBAE nanoparticle is further taught to encapsulate at least one DNA or RNA molecule capable of encoding a gene-editing or therapeutic protein (claim 1) and the weight ratio of PBAE polymer to encapsulated DNA is taught to be “between 5-200, and in some embodiments 30-90 w/w” (claim 22). In particular the particle formed from polymer 7,8-4-J11, which encapsulated a nucleic acid molecule at a 30 w/w ratio, was found to transfect cells more efficiently than other higher ratio PBAE polymers (Fig. 71 and 76, pg. 188 section 8.3.1, and pg. 190-191 section 8.3.4).
It would have been prima facie obvious to a person of ordinary skill in the art, prior to the filing of the instant application, to modify the invention rendered obvious by the teachings of Rui and Lou with the teachings of Green because use of a known technique in similar products to improve efficacy yields predictable results. The teachings of Rui and Lou rendered obvious NPs formed from the biodegradable PBAE polymer B7-S90, Sc12-E63, 50%/50% S90/Sc12 at 60% w/w and 10% w/w DMG-PEG2k which encapsulate RVG-SAM, have polydispersity in the range of 0.13-0.24, and have a zeta-potential of <5 mV. Rui and Lou also rendered obvious a kit comprising B7-S90, Sc12-E63, 50%/50% S90/Sc12, DMG-PEG2k, and RVG-SAM.
In view of the teachings of Green, one of ordinary skill in the art would be motivated to formulate their nanoparticle with the PBAE polymers at a 30 w/w ratio with the RVG-SAM because Green teaches this ratio to be particularly effective at delivering encapsulated nucleic acid molecules to their targeted cells and an ordinary artisan would recognize this as desirable. Rui teaches only one w/w ratio while Green teaches a range of suitable ratios, highlighting the efficacy achieved with a ratio of 30 w/w. A person of ordinary skill would desire optimal efficacy in an mRNA vaccine delivered via PBAE polymer nanoparticle and would therefore be motivated to use the 30 w/w ratio to pursue improved efficacy. As a result, there is a reasonable expectation of success in arriving at the invention of claim 24 in view of the teachings of Rui and Lou and further in view of the teachings of Green.
Claims 30-31 are rejected under 35 U.S.C. 103 as being unpatentable over Rui (Dissertation, Johns Hopkins University, June 2021, provided by Applicant in the IDS filed on 7 May 2024) in view of Lou (J. Control. Rel. 2020, 325, 370., provided by Applicant in the IDS filed on 7 May 2024) as applied to claims 1-2, 6, 10-11, 15-18, 20-23, 25, 27-29, and 60 above, and further in view of Selvaraj et al. (J. Vaccines Vaccin. 2015, 6 (4), 1000292., hereafter referred to as Selvaraj).
Rui and Lou have been described above.
Rui and Lou do not teach the nanoparticle to comprise MgCl2 (claims 30-31). These deficiencies are offset by the teachings of Selvaraj.
Selvaraj teaches the preparation of a liquid state rabies vaccine with MgCl2 as a stabilizer and adjuvant (Title and Abstract). When used in a polio vaccine administered to humans, Selvaraj teaches that MgCl2 present in the vaccine acted as both a stabilizer and adjuvant, “boosting the immune response when combined with polio vaccine” (pg. 3, right col., final para.). Selvaraj found that their rabies vaccine maintained immunogenicity with added MgCl2 (Tables 3-4 and Conclusion).
It would have been prima facie obvious to a person of ordinary skill in the art, prior to the filing of the instant application, to combine the teachings of Selvaraj with the invention rendered obvious by the teachings of Rui and Lou because combining prior art elements to impart known benefits produces predictable results. The teachings of Rui and Lou rendered obvious NPs formed from the biodegradable PBAE polymer B7-S90, Sc12-E63, 50%/50% S90/Sc12 at 60% w/w and 10% w/w DMG-PEG2k which encapsulate RVG-SAM, have polydispersity in the range of 0.13-0.24, and have a zeta-potential of <5 mV. Rui and Lou also rendered obvious a kit comprising B7-S90, Sc12-E63, 50%/50% S90/Sc12, DMG-PEG2k, and RVG-SAM.
In view of the teachings of Selvaraj, one of ordinary skill in the art would be motivated to modify the nanoparticles rendered obvious above to also comprise MgCl2 because Selvaraj teaches the excipient to provide stability to vaccines and to possible enhance the immune response of subjects following administration. An ordinary artisan would desire their NP-encapsulated mRNA vaccine to be stable and have enhanced immunogenicity and would therefore be motivated to include MgCl2 in their nanoparticles. In addition, Selvaraj teaches that a rabies vaccine is compatible with MgCl2 and that immunogenicity was maintained in the presence of the salt, which would further motivate its inclusion. As a result, there is a reasonable expectation of success in arriving at the invention of instant claims 30-31 in view of the teachings of Rui and Lou and further in view of the teachings of Selvaraj.
Claims 1-2, 6, 10-11, 15, 17-18, 20-23, 25, 27-29, and 60 are rejected under 35 U.S.C. 103 as being unpatentable over Kaczmarek et al. (Nano Lett. 2018, 18 (10), 6449., provided by Applicant in the IDS filed on 7 May 2024, hereafter referred to as Kaczmarek) in view of Green et al. (Acc. Chem. Res. 2008, 41 (6), 749., hereafter referred to as Green 2) and Lou (J. Control. Rel. 2020, 325, 370., provided by Applicant in the IDS filed on 7 May 2024).
Kaczmarek teaches the formation of nanoparticles from biodegradable poly(beta-amino ester) (PBAE) polymers and PEG-lipids to encapsulate and deliver mRNA (Abstract). Therapeutic uses of mRNA are taught to have spurred a great amount of research, but delivery of mRNA is taught to be difficult due to “a number of barriers, including RNase-mediated degradation, cellular entry, and endosomal escape” (pg. 6449, Introduction, para. 1). Kaczmarek previously demonstrated delivery of mRNA via PBAE-based nanoparticles (NPs) and reports that they have improved their delivery system, resulting in “a multiple order-of-magnitude increase in potency of mRNA delivery in vivo” (pg. 6449-6450, Introduction, para. 2). In one embodiment, the PBAE-based NP taught by Kaczmarek is formed via the synthetic method outlined in the Supplemental Information, pg. 1, in which bisphenol A glycerolate diacrylate (equivalent to B7 in the instant application following polymerization as evidenced by Table 1 of the instant spec.), 4-(2-amino ethyl) morpholine (equivalent to S90 in the instant application following polymerization as evidenced by Table 1 of the instant spec.), and dodecyl amine (equivalent to Sc12 in the instant application following polymerization as evidenced by Table 1 of the instant spec.) are polymerized in N,N-dimethylformamide and subsequently end-capped with 1,3-diaminopropane (equivalent to end-cap E1 in the instant application following polymerization as evidenced by Table 1 of the instant spec.).
Further, Kaczmarek teaches that formulating the NPs with a PEG-lipid “can enhance function” and that 7% w/w is a suitable amount to use (pg. 6450, left col., final para.). In Table S2, Kaczmarek teaches that the ratio of hydrophilic to hydrophobic monomers should be 1-1.2, which is equivalent to a range of 50%/50% to ~54.5%/45.5%. Finally, Kaczmarek teaches that their PBAE NPs successfully encapsulated luciferase-coding mRNA (pg. 6451, right col., para. 1 and Fig. 3).
Kaczmarek does not teach the end-cap of the PBAE polymer to be diethylenetriamine (E63), the encapsulated mRNA to be a self-amplifying mRNA (SAM) that encodes a rabies virus glycoprotein, the nanoparticle to have a zeta-potential of -12 to +18 mV, the polydispersity of a composition comprising a plurality of nanoparticles, nor the PEG-lipid to be DMG-PEG2k. These deficiencies are offset by the teachings of Green 2 and Lou.
Green 2 teaches a high-throughput synthesis and screening approach to designing biodegradable PBAE polymers for the purpose of gene delivery (Abstract). Green 2 found that the “terminal monomer unit of the polymer can be crucial to the efficacy of the overall polymer” and synthesized a library of polymers with various amine monomers as end-caps (pg. 756, Terminal Groups of a Polymer Are Key for Gene Delivery Efficacy and Figure 9). Green 2 highlights amine end-caps 1,3-diaminopropane (noted as 103 in Fig. 9C) and 1,3-diaminopentane (noted as 117 in Fig. 9C) as being “lead modified polymers” for encapsulating DNA, but in another embodiment Fig. 9C teaches diethylenetriamine (noted as 125 in Fig. 9C) (pg. 756, Terminal Groups of a Polymer Are Key for Gene Delivery Efficacy and Figure 9). The end-modified PBAE polymers are taught to have “gene delivery efficacy comparable to lentivirus and adenovirus”, 2 orders of magnitude higher efficacy than the previous “’gold standard’ for polymeric transfection, 25 kDa polyethylenimine”, and 2 orders of magnitude lower toxicity than 25 kDa polyethylenimine (pg. 757, left col., para. 1). Finally, Green 2 teaches that the amine end-caps on the PBAE polymers increased gene expression levels following intraperitoneal injection in mice subjects as compared to PBAE polymers without amine end-caps and that end-modification altered biodistribution, motivating “a more detailed inquiry into the structure/function relationships of [the PBAE] polymers” (pg. 757, In Vivo Gene Delivery).
Lou has been described above.
Guidelines on the obviousness of similar and overlapping ranges, amounts, and proportions are provided in MPEP § 2144.05. With respect to claimed ranges which “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). These guidelines apply to the amount of the compound of formula (I) and DMG-PEG2k in the nanoparticles, the ratio of hydrophilic to hydrophobic monomers in the PBAE polymer, and the zeta-potential and polydispersity of the nanoparticles. In each instance, the prior art taught values or ranges that fell within or significantly overlapped with the ranges recited in the instant claims.
It would have been prima facie obvious to a person of ordinary skill in the art, prior to the filing of the instant application, to combine the teachings of Kaczmarek, Green 2, and Lou to arrive at the invention of instant claims 1-2, 6, 10-11, 15-18, 20-23, 25, 27-29, and 60 because combining prior art elements according to known methods to enable new applications produces predictable results. Kaczmarek teaches NPs formed from biodegradable PBAE polymers which in one embodiment are formed from bisphenol A glycerolate diacrylate (equivalent to B7), 4-(2-amino ethyl) morpholine (equivalent to S90), and dodecyl amine (equivalent to Sc12), end-capped by a diamine. Further, Kaczmarek teaches formulating their NPs with a PEG-lipid to enhance function, a range of ratios of hydrophilic to hydrophobic monomers that contains the equivalent to 50%/50%, and the encapsulation of mRNA.
In view of the teachings of Green 2, a person of ordinary skill in the art would be motivated to use diethylenetriamine (equivalent to E63) as the amine end-cap in the PBAE polymer taught by Kaczmarek because Green 2 teaches it to be an amine suitable for use in PBAE polymers for the encapsulation and delivery of nucleic acid molecules. While Green 2 highlights the amines 1,3-diaminopropane, the same end-cap used as an example by Kaczmarek, and 1,3-diaminopentane among their group of amine end-caps, they highlight the amines for the encapsulation and delivery of DNA. The ordinary artisan would be motivated to use an end-cap that is optimal for the encapsulation and delivery of mRNA and would find it obvious to optimize for mRNA delivery with the other amines taught by Green 2 in Fig. 9C. Green 2 further teaches that the identity of the amine end-cap alters biodistribution following administration and that a more detailed inquiry into the structure/function relationships of PBAE polymers is required. It would have been within the capabilities of a person of ordinary skill to experiment and optimize within the Markush group of amines taught by Green 2 in Fig. 9C to arrive at diethylenetriamine as the end-cap for the PBAE polymer taught by Kaczmarek. See MPEP § 2144.05.II.
In view of the teachings of Lou, one of ordinary skill in the art would be motivated to select the RVG-SAM as the mRNA cargo because Lou teaches the nucleic acid to be capable of encoding RVG, the only target for neutralizing antibodies for rabies, and that they can be successfully and efficiently encapsulated in lipid NPs. The ordinary artisan would recognize the application of NP-encapsulated SAMs as vaccines in treating rabies and would be motivated to combine the RVG-SAM with the biodegradable PBAE NP. In addition, Lou teaches that lipid NPs that successfully and efficiently encapsulate RVG-SAM and deliver the mRNA vaccine to cells have polydispersity in the range of 0.13-0.24 and a zeta-potential of <5 mV. The ordinary artisan would desire their NPs to encapsulate and deliver the RVG-SAM successfully and would therefore be motivated to formulate their nanoparticles to have those physicochemical characteristics. Finally, the ordinary artisan would be motivated to select DMG-PEG2000 (equivalent to the elected DMG-PEG2k) as the PEG-lipid in the nanoparticle taught by Kaczmarek because Lou teaches DMG-PEG2000 to be suitable for use in a NP that encapsulates RNA for use as a vaccine.
Kaczmarek, Green 2, and Lou are silent regarding a kit. However, the Applicant elected the specific contents of the kit to comprise the compound B7-S90, Sc12-E63, 50%/50% ratio of S90/Sc12, DMG-PEG2k, and the SAM that encodes a rabies virus glycoprotein. The teachings of Rui and Lou have rendered obvious a nanoparticle comprising the compound B7-S90, Sc12-E63, 50%/50% ratio of S90/Sc12, DMG-PEG2k, and RVG-SAM, therefore a kit comprising those three species is also obvious. As a result, there is a reasonable expectation of success in arriving at the invention of instant claims 1-2, 6, 10-11, 15-18, 20-23, 25, 27-29, and 60 in view of the teachings of Kaczmarek, Green 2, and Lou.
Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over Kaczmarek (Nano Lett. 2018, 18 (10), 6449., provided by Applicant in the IDS filed on 7 May 2024) in view of Green 2 (Acc. Chem. Res. 2008, 41 (6), 749.) and Lou (J. Control. Rel. 2020, 325, 370., provided by Applicant in the IDS filed on 7 May 2024) as applied to claims 1-2, 6, 10-11, 15-18, 20-23, 25, 27-29, and 60 above, and further in view of Green et al. (WIPO International Patent Publication No. WO 2020/077159 A1, published on 16 April 2020, provided by Applicant in the IDS filed on 7 May 2024).
Kaczmarek, Green 2, and Lou have been described above.
Kaczmarek, Green 2, and Lou do not teach the PBAE polymer to comprise >50% w/w of the nanoparticle. This deficiency is offset by the teachings of Green 3.
Green 3 teaches PEG-PBAE co-polymers and their use for delivering genes, drugs, and other active agents (Abstract). The co-polymers are taught to form particles which may encapsulate cargo such as RNA (claims 1 and 5-6) and the weight ratio of the PBAE-containing polymer to the cargo is taught to be 30-90 w/w (claim 8). In Example 5, Green 3 teaches that a 60 w/w ratio particle is formed by mixing 3.6 mg/mL polymer solution with 0.06 mg/mL nucleic acid solution at equal volumes, demonstrating that the 60 w/w ratio also results in a particle that is 85% w/w of the entire particle which falls within the range recited in instant claim 16. Finally, Green 3 teaches that changes in the ratios of monomers can impact the function of resulting polymers and that ratios appropriate to use in PBAE polymers that will be used to encapsulate nucleic acids include 1:1, which is equivalent to the 50%/50% recited in instant claim 15 (col. 2 lines 25-28, col. 8 lines 52-54, Fig. 3, and Examples 4 and 8).
It would have been prima facie obvious to a person of ordinary skill in the art, prior to the filing of the instant application, to modify the invention rendered obvious by the teachings of Kaczmarek, Green 2, and Lou with the teachings of Green 3 because use of a known technique in similar products to improve efficacy yields predictable results. The teachings of Kaczmarek, Green 2, and Lou rendered obvious NPs formed from the biodegradable PBAE polymer B7-S90, Sc12-E63, 50%/50% S90/Sc12 at 60% w/w and 7% w/w DMG-PEG2k which encapsulate RVG-SAM, have polydispersity in the range of 0.13-0.24, and have a zeta-potential of <5 mV, as well as a kit comprising the same.
One of ordinary skill would be motivated to formulate their nanoparticle to comprise ~85% by weight PBAE polymer in view of the teachings of Green 3 because Kaczmarek, Green 2, and Lou do not teach an amount of polymer to be used in their nanoparticle and Green 3 provides information the ordinary artisan would need to complete their invention. Further, Green 3 teaches that this weight is appropriate for a nanoparticle comprising polymers that is intended to encapsulate RNA, which the ordinary artisan would recognize as relevant to their invention. As a result, there is a reasonable expectation of success in arriving at the invention of instant claim 16 in view of the teachings of Kaczmarek, Green 2, and Lou and further in view of the teachings of Green 3.
Claim 24 is rejected under 35 U.S.C. 103 as being unpatentable over Kaczmarek (Nano Lett. 2018, 18 (10), 6449., provided by Applicant in the IDS filed on 7 May 2024) in view of Green 2 (Acc. Chem. Res. 2008, 41 (6), 749.) and Lou (J. Control. Rel. 2020, 325, 370., provided by Applicant in the IDS filed on 7 May 2024) as applied to claims 1-2, 6, 10-11, 15-18, 20-23, 25, 27-29, and 60 above, and further in view of Green (WIPO International Patent Publication No. WO 2020/077159 A1, published on 16 April 2020, provided by Applicant in the IDS filed on 7 May 2024).
Kaczmarek, Green 2, and Lou have been described above.
Kaczmarek, Green 2, and Lou do not teach the compound of formula (I) to be present in a ratio of 30:1 with the SAM (claim 24). These deficiencies are offset by the teachings of Green.
Green has been described above.
It would have been prima facie obvious to a person of ordinary skill in the art, prior to the filing of the instant application, to modify the invention rendered obvious by the teachings of Kaczmarek, Green 2, and Lou with the teachings of Green because use of a known technique in similar products to improve efficacy yields predictable results. The teachings of Kaczmarek, Green 2, and Lou rendered obvious NPs formed from the biodegradable PBAE polymer B7-S90, Sc12-E63, 50%/50% S90/Sc12 at 60% w/w and 7% w/w DMG-PEG2k which encapsulate RVG-SAM, have polydispersity in the range of 0.13-0.24, and have a zeta-potential of <5 mV, as well as a kit comprising the same.
In view of the teachings of Green, one of ordinary skill in the art would be motivated to formulate their nanoparticle with the PBAE polymers at a 30 w/w ratio with the RVG-SAM because Green teaches this ratio to be particularly effective at delivering encapsulated nucleic acid molecules to their targeted cells and an ordinary artisan would recognize this as desirable. A person of ordinary skill would desire optimal efficacy in an mRNA vaccine delivered via PBAE polymer nanoparticle and would therefore be motivated to use the 30 w/w ratio to pursue improved efficacy. As a result, there is a reasonable expectation of success in arriving at the invention of claim 24 in view of the teachings of Kaczmarek, Green 2, and Lou and further in view of the teachings of Green.
Claims 30-31 are rejected under 35 U.S.C. 103 as being unpatentable over Kaczmarek (Nano Lett. 2018, 18 (10), 6449., provided by Applicant in the IDS filed on 7 May 2024) in view of Green 2 (Acc. Chem. Res. 2008, 41 (6), 749.) and Lou (J. Control. Rel. 2020, 325, 370., provided by Applicant in the IDS filed on 7 May 2024) as applied to claims 1-2, 6, 10-11, 15-18, 20-23, 25, 27-29, and 60 above and further in view of Selvaraj (J. Vaccines Vaccin. 2015, 6 (4), 1000292.).
Rui and Lou have been described above.
Rui and Lou do not teach the nanoparticle to comprise MgCl2 (claims 30-31). These deficiencies are offset by the teachings of Selvaraj.
Selvaraj has been described above.
It would have been prima facie obvious to a person of ordinary skill in the art, prior to the filing of the instant application, to combine the teachings of Selvaraj with the invention rendered obvious by the teachings of Kaczmarek, Green 2, and Lou because combining prior art elements to impart known benefits produces predictable results. The teachings of Kaczmarek, Green 2, and Lou rendered obvious NPs formed from the biodegradable PBAE polymer B7-S90, Sc12-E63, 50%/50% S90/Sc12 at 60% w/w and 10% w/w DMG-PEG2k which encapsulate RVG-SAM, have polydispersity in the range of 0.13-0.24, and have a zeta-potential of <5 mV, as well as a kit comprising the same.
In view of the teachings of Selvaraj, one of ordinary skill in the art would be motivated to modify the nanoparticles rendered obvious above to also comprise MgCl2 because Selvaraj teaches the excipient to provide stability to vaccines and to possible enhance the immune response of subjects following administration. An ordinary artisan would desire their NP-encapsulated mRNA vaccine to be stable and have enhanced immunogenicity and would therefore be motivated to include MgCl2 in their nanoparticles. In addition, Selvaraj teaches that a rabies vaccine is compatible with MgCl2 and that immunogenicity was maintained in the presence of the salt, which would further motivate its inclusion. As a result, there is a reasonable expectation of success in arriving at the invention of instant claims 30-31 in view of the teachings of Kaczmarek, Green 2, and Lou and further in view of the teachings of Selvaraj.
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 1-2, 6, 10-11, 15-18, 20-25, 27-31, and 60 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 43-44 of copending Application No. 18/859,372 in view of Green et al. (U.S. Patent No. 11,401,380 B2, priority to 28 March 2016, hereafter referred to as Green 3), Lou (J. Control. Rel. 2020, 325, 370., provided by Applicant in the IDS filed on 7 May 2024), Green (WIPO International Patent Publication No. WO 2020/077159 A1, published on 16 April 2020, provided by Applicant in the IDS filed on 7 May 2024), and Selvaraj (J. Vaccines Vaccin. 2015, 6 (4), 1000292.).
This is a provisional nonstatutory double patenting rejection.
Copending Application No. 18/859,372 recites a nanoparticle comprising a PBAE polymer of the formula 7-90_c12(50%)-63, which is identical to the elected PBAE polymer B7-S90, Sc12-E63, 50%/50% S90/Sc12, the PEGylated lipid DMG-PEG2000, which is equivalent to the elected DMG-PEG2k, and a nucleic acid which comprises mRNA (claim 43). The DMG-PEG2000 is recited as comprising 5-20% w/w of the nanoparticle and the nanoparticles are recited as having a zeta-potential of 2-6 mV (claim 44).
Copending Application No. 18/859,372 does not recite the amount of the nanoparticle by weight represented by the PBAE polymer, the ratio of substituents in the PBAE polymer, the polydispersity of a solution comprising the nanoparticles, the weight ratio of the PBAE polymer to the mRNA, the mRNA to be a self-amplifying mRNA (SAM) that encodes a rabies virus glycoprotein, nor the nanoparticle to comprise MgCl2. These deficiencies are offset by the teachings of Green 3, Lou, Green, and Selvaraj.
Green 3, Lou, Green, and Selvaraj have been described above and particularly relevant to 60, Green teaches a kit comprising a nanoparticle formed from PBAE polymer encapsulating an RNA molecule, a pharmaceutically acceptable carrier, and instruction for use (claims 1 and 27-28).
Instant claims 1-2, 6, 10-11, 15-18, 20-25, 27-31, and 60 are obvious variations of copending Application No. 18/859,372 because it would have been prima facie obvious to a person of ordinary skill in the art at the time of filing to modify the nanoparticle recited by Application ‘372 to use the amount of PBAE polymer in the nanoparticle and the ratio of substituents in the PBAE polymer taught by Green 3, to use the polydispersity of a solution comprising the nanoparticles and RVG-SAM taught by Lou, to use the weight ratio of the PBAE polymer to the mRNA taught by Green, and to comprise MgCl2 as taught by Selvaraj.
One of ordinary skill would be motivated to formulate their nanoparticle to comprise ~85% by weight PBAE polymer in view of the teachings of Green 3 because Application ‘372 does not teach an amount of polymer to be used in their nanoparticle and Green 3 provides information the ordinary artisan would need to complete their invention. Further, Green 3 teaches that this weight is appropriate for a nanoparticle comprising polymers that is intended to encapsulate RNA, which the ordinary artisan would recognize as relevant to their invention. A person of ordinary skill would also be motivated to use the ratio of substituents taught by Green 3 because Application ‘372 does not teach a ratio and Green 3 provides information the ordinary artisan would need to complete their invention, as well as teaching that this weight is appropriate for a polymer that is intended to form a nanoparticle and encapsulate RNA, which the ordinary artisan would recognize as relevant to their invention.
In view of the teachings of Lou, one of ordinary skill in the art would be motivated to select the RVG-SAM as the RNA cargo because Lou teaches the nucleic acid to be capable of encoding RVG, the only target for neutralizing antibodies for rabies, and that they can be successfully and efficiently encapsulated in lipid NPs. The ordinary artisan would recognize the application of NP-encapsulated SAMs as vaccines in treating rabies and would be motivated to combine the RVG-SAM with the NP recited in Application ‘372. In addition, Lou teaches that lipid NPs that successfully and efficiently encapsulate RVG-SAM and deliver the mRNA vaccine to cells have polydispersity in the range of 0.13-0.24 and a zeta-potential of <5 mV. The ordinary artisan would desire their NPs to encapsulate and deliver the RVG-SAM successfully and would therefore be motivated to formulate their nanoparticles to have those physicochemical characteristics.
In view of the teachings of Green, one of ordinary skill in the art would be motivated to formulate their nanoparticle with the PBAE polymers at a 30 w/w ratio with the RVG-SAM because Green teaches this ratio to be particularly effective at delivering encapsulated nucleic acid molecules to their targeted cells and an ordinary artisan would recognize this as desirable. A person of ordinary skill would desire optimal efficacy in an mRNA vaccine delivered via PBAE polymer nanoparticle and would therefore be motivated to use the 30 w/w ratio to pursue improved efficacy, particularly when Application ‘372 does not recite an appropriate ratio to be used. The ordinary artisan would also find it obvious to create a kit comprising the nanoparticle above because Green teaches it as a practical application of the nanoparticle.
Finally, in view of the teachings of Selvaraj, one of ordinary skill in the art would be motivated to modify the nanoparticles above to also comprise MgCl2 because Selvaraj teaches the excipient to provide stability to vaccines and to have the capability to enhance the immune response of subjects following administration. An ordinary artisan would desire their NP-encapsulated mRNA vaccine to be stable and have enhanced immunogenicity and would therefore be motivated to include MgCl2 in their nanoparticles. In addition, Selvaraj teaches that a rabies vaccine is compatible with MgCl2 and that immunogenicity was maintained in the presence of the salt, which would further motivate its inclusion.
Claims 1-2, 6, 10-11, 15-18, 20-25, 27-31, and 60 are directed to an invention not patentably distinct from claims 43-44 of commonly assigned copending Application No. 18/859,372 in view of Green 3, Lou, Green, and Selvaraj. Specifically, see above.
The U.S. Patent and Trademark Office may not institute a derivation proceeding in the absence of a timely filed petition. The USPTO normally will not institute a derivation proceeding between applications or a patent and an application having common ownership (see 37 CFR 42.411). Commonly assigned copending Application No. 18/859,372, discussed above, may form the basis for a rejection of the noted claims under 35 U.S.C. 102 or 103 if the commonly assigned case qualifies as prior art under 35 U.S.C. 102(a)(2) and the patentably indistinct inventions were not commonly owned or deemed to be commonly owned not later than the effective filing date under 35 U.S.C. 100(i) of the claimed invention.
In order for the examiner to resolve this issue the applicant or patent owner can provide a statement under 35 U.S.C. 102(b)(2)(C) and 37 CFR 1.104(c)(4)(i) to the effect that the subject matter and the claimed invention, not later than the effective filing date of the claimed invention, were owned by the same person or subject to an obligation of assignment to the same person. Alternatively, the applicant or patent owner can provide a statement under 35 U.S.C. 102(c) and 37 CFR 1.104(c)(4)(ii) to the effect that the subject matter was developed and the claimed invention was made by or on behalf of one or more parties to a joint research agreement that was in effect on or before the effective filing date of the claimed invention, and the claimed invention was made as a result of activities undertaken within the scope of the joint research agreement; the application must also be amended to disclose the names of the parties to the joint research agreement.
A showing that the inventions were commonly owned or deemed to be commonly owned not later than the effective filing date under 35 U.S.C. 100(i) of the claimed invention will preclude a rejection under 35 U.S.C. 102 or 103 based upon the commonly assigned case. Alternatively, applicant may take action to amend or cancel claims such that the applications, or the patent and the application, no longer contain claims directed to patentably indistinct inventions.
Claims 1-2, 6, 10-11, 15-18, 20-25, 27-31, and 60 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 11-13, and 18 of copending Application No. 19/122,923 in view of Green 3 (U.S. Patent No. 11,401,380 B2, priority to 28 March 2016), Lou (J. Control. Rel. 2020, 325, 370., provided by Applicant in the IDS filed on 7 May 2024), and Selvaraj (J. Vaccines Vaccin. 2015, 6 (4), 1000292.).
This is a provisional nonstatutory double patenting rejection.
Copending Application No. 19/122,923 recites a nanoparticle comprising a PBAE polymer and at least one mRNA molecule, wherein the PBAE polymer may have the same backbone as recited in instant claim 1, substituents B7, S90, and Sc12, and be end-capped by E63 (claims 1-5 and 11). The weight ratio of PBAE polymer to mRNA is recited to be 100:1 to 5:1, in some embodiments 30:1 (claims 12-13). Finally, Application ‘923 recites the nanoparticle to comprise a PEG-lipid (claim 18).
Copending Application No. 19/122,923 does not recite the ratio of substituents in the PBAE polymer, the amount of the nanoparticle by weight represented by the PBAE polymer, the PEG-lipid to be DMG-PEG2k, the amount of the PEG-lipid, the zeta-potential of the nanoparticles, the polydispersity of a solution comprising the nanoparticles, the mRNA to be a self-amplifying mRNA (SAM) that encodes a rabies virus glycoprotein, nor the nanoparticle to comprise MgCl2. These deficiencies are offset by the teachings of Green 3, Lou, and Selvaraj.
Green 3, Lou, and Selvaraj have been described above and particularly relevant to instant claim 20, Lou teaches that DMG-PEG2000 is appropriate to use at 2% (pg. 371, 2.3. Formulation of SAM lipid nanoparticles and Table 1).
Instant claims 1-2, 6, 10-11, 15-18, 20-25, 27-31, and 60 are obvious variations of copending Application No. 19/122,923 because it would have been prima facie obvious to a person of ordinary skill in the art at the time of filing to modify the nanoparticle recited by Application ‘923 to use the amount of PBAE polymer in the nanoparticle and the ratio of substituents in the PBAE polymer taught by Green 3, to use DMG-PEG2000 in an amount of 2%, the polydispersity of a solution comprising the nanoparticles, the zeta-potential of the nanoparticles, and RVG-SAM taught by Lou, and to comprise MgCl2 as taught by Selvaraj.
One of ordinary skill would be motivated to formulate their nanoparticle to comprise ~85% by weight PBAE polymer in view of the teachings of Green 3 because Application ‘923 does not teach an amount of polymer to be used in their nanoparticle and Green 3 provides information the ordinary artisan would need to complete their invention. Further, Green 3 teaches that this weight is appropriate for a nanoparticle comprising polymers that is intended to encapsulate RNA, which the ordinary artisan would recognize as relevant to their invention. A person of ordinary skill would also be motivated to use the ratio of substituents taught by Green 3 because Application ‘923 does not teach a ratio and Green 3 provides information the ordinary artisan would need to complete their invention, as well as teaching that this weight is appropriate for a polymer that is intended to form a nanoparticle and encapsulate RNA, which the ordinary artisan would recognize as relevant to their invention.
In view of the teachings of Lou, one of ordinary skill in the art would be motivated to select the RVG-SAM as the RNA cargo because Lou teaches the nucleic acid to be capable of encoding RVG, the only target for neutralizing antibodies for rabies, and that they can be successfully and efficiently encapsulated in lipid NPs. The ordinary artisan would recognize the application of NP-encapsulated SAMs as vaccines in treating rabies and would be motivated to combine the RVG-SAM with the NP recited in Application ‘923. In addition, Lou teaches that lipid NPs that successfully and efficiently encapsulate RVG-SAM and deliver the mRNA vaccine to cells have polydispersity in the range of 0.13-0.24 and a zeta-potential of <5 mV. The ordinary artisan would desire their NPs to encapsulate and deliver the RVG-SAM successfully and would therefore be motivated to formulate their nanoparticles to have those physicochemical characteristics. Further, the ordinary artisan would be motivated to select DMG-PEG2000 as the PEG-lipid in the invention recited by Application ‘923 because the copending Application recites the genus PEG-lipid but does not recite a specific species and Lou teaches DMG-PEG2000 to be suitable for use in a nanoparticle that encapsulates RNA for use as a vaccine. In addition, Lou teaches that DMG-PEG2000 is appropriate to use at 2% and Application ‘923 does not recite a quantity of PEG-lipid to be used, which would motivate one of ordinary skill to use the quantity taught by Lou.
Finally, in view of the teachings of Selvaraj, one of ordinary skill in the art would be motivated to modify the nanoparticles above to also comprise MgCl2 because Selvaraj teaches the excipient to provide stability to vaccines and to have the capability to enhance the immune response of subjects following administration. An ordinary artisan would desire their NP-encapsulated mRNA vaccine to be stable and have enhanced immunogenicity and would therefore be motivated to include MgCl2 in their nanoparticles. In addition, Selvaraj teaches that a rabies vaccine is compatible with MgCl2 and that immunogenicity was maintained in the presence of the salt, which would further motivate its inclusion.
Application ‘923, Green 3, Lou, and Selvaraj are silent regarding a kit. However, the Applicant elected the specific contents of the kit to comprise the compound B7-S90, Sc12-E63, 50%/50% ratio of S90/Sc12, DMG-PEG2k, and the SAM that encodes a rabies virus glycoprotein. The invention recited by Application ‘923 in view of the teachings of Green 3, Lou, and Selvaraj have rendered obvious a nanoparticle comprising the compound B7-S90, Sc12-E63, 50%/50% ratio of S90/Sc12, DMG-PEG2k, and RVG-SAM, therefore a kit comprising those three species is also obvious.
Claims 1-2, 6, 10-11, 15-18, 20-25, 27-31, and 60 are directed to an invention not patentably distinct from claims 1-5, 11-13, and 18 of commonly assigned copending Application No. 19/122,923 in view of Green 3, Lou, and Selvaraj. Specifically, see above.
The U.S. Patent and Trademark Office may not institute a derivation proceeding in the absence of a timely filed petition. The USPTO normally will not institute a derivation proceeding between applications or a patent and an application having common ownership (see 37 CFR 42.411). Commonly assigned copending Application No. 19/122,923, discussed above, may form the basis for a rejection of the noted claims under 35 U.S.C. 102 or 103 if the commonly assigned case qualifies as prior art under 35 U.S.C. 102(a)(2) and the patentably indistinct inventions were not commonly owned or deemed to be commonly owned not later than the effective filing date under 35 U.S.C. 100(i) of the claimed invention.
In order for the examiner to resolve this issue the applicant or patent owner can provide a statement under 35 U.S.C. 102(b)(2)(C) and 37 CFR 1.104(c)(4)(i) to the effect that the subject matter and the claimed invention, not later than the effective filing date of the claimed invention, were owned by the same person or subject to an obligation of assignment to the same person. Alternatively, the applicant or patent owner can provide a statement under 35 U.S.C. 102(c) and 37 CFR 1.104(c)(4)(ii) to the effect that the subject matter was developed and the claimed invention was made by or on behalf of one or more parties to a joint research agreement that was in effect on or before the effective filing date of the claimed invention, and the claimed invention was made as a result of activities undertaken within the scope of the joint research agreement; the application must also be amended to disclose the names of the parties to the joint research agreement.
A showing that the inventions were commonly owned or deemed to be commonly owned not later than the effective filing date under 35 U.S.C. 100(i) of the claimed invention will preclude a rejection under 35 U.S.C. 102 or 103 based upon the commonly assigned case. Alternatively, applicant may take action to amend or cancel claims such that the applications, or the patent and the application, no longer contain claims directed to patentably indistinct inventions.
Claims 1-2, 6, 10-11, 15-18, 20-25, 27-31, and 60 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 6, 13, 15, 17, 28, 34, and 54 of copending Application No. 18/693,984 in view of Green 3 (U.S. Patent No. 11,401,380 B2, priority to 28 March 2016) and Lou (J. Control. Rel. 2020, 325, 370., provided by Applicant in the IDS filed on 7 May 2024).
This is a provisional nonstatutory double patenting rejection.
Copending Application No. 18/693,984 recites a composition comprising a PBAE polymer wherein the PBAE polymer may have the same backbone as recited in instant claim 1, substituents B7, S90, and Sc12 and be end-capped by E63, resulting in the polymer B7-S90,Sc12-E63 with a 50%/50% ratio of S90/Sc12 which is identical to the elected PBAE polymer (claims 1-2, 6, and 13). The polymer is recited as encapsulating a nucleic acid and the weight ratio of polymer to nucleic acid is recited as being between 30-200 (claims 1 and 15). Application ‘984 recites the nucleic acid to be a SAM in one embodiment (claim 17) and the nanoparticle to comprise the lipid-PEG DMG-PEG2k (claim 28). Finally, Application ‘984 recites the composition of claim 1 to comprise the excipient MgCl2 (claim 34) and a kit comprising the PBAE polymer of formula (I) in claim 1, nucleic acids, reagents, and instructions for use (claim 54).
Copending Application No. 18/693,984 does not recite the amount of the nanoparticle by weight represented by the PBAE polymer, the amount of DMG-PEG2k, the zeta-potential of the nanoparticles, the polydispersity of a solution comprising the nanoparticles, nor the SAM to encode a rabies virus glycoprotein. These deficiencies are offset by the teachings of Green 3 and Lou.
Green 3 and Lou have been described above.
Instant claims 1-2, 6, 10-11, 15-18, 20-25, 27-31, and 60 are obvious variations of copending Application No. 18/693,984 because it would have been prima facie obvious to a person of ordinary skill in the art at the time of filing to modify the nanoparticle recited by Application ‘372 to use the amount of PBAE polymer in the nanoparticle taught by Green 3 and to use the quantity of DMG-PEG2k, to formulate the nanoparticles with the zeta-potential, to use the polydispersity of a solution comprising the nanoparticles, and to select the RNA RVG-SAM taught by Lou.
One of ordinary skill would be motivated to formulate their nanoparticle to comprise ~85% by weight PBAE polymer in view of the teachings of Green 3 because Application ‘984 does not teach an amount of polymer to be used in their nanoparticle and Green 3 provides information the ordinary artisan would need to complete their invention. Further, Green 3 teaches that this weight is appropriate for a nanoparticle comprising polymers that is intended to encapsulate RNA, which the ordinary artisan would recognize as relevant to their invention.
In view of the teachings of Lou, one of ordinary skill in the art would be motivated to select the RVG-SAM as the RNA cargo because Lou teaches the nucleic acid to be capable of encoding RVG, the only target for neutralizing antibodies for rabies, and that they can be successfully and efficiently encapsulated in lipid NPs. The ordinary artisan would recognize the application of NP-encapsulated SAMs as vaccines in treating rabies and would be motivated to combine the RVG-SAM with the NP recited in Application ‘984. In addition, Lou teaches that lipid NPs that successfully and efficiently encapsulate RVG-SAM and deliver the mRNA vaccine to cells have polydispersity in the range of 0.13-0.24 and a zeta-potential of <5 mV. The ordinary artisan would desire their NPs to encapsulate and deliver the RVG-SAM successfully and would therefore be motivated to formulate their nanoparticles to have those physicochemical characteristics. Further, the ordinary artisan would be motivated to use 2% DMG-PEG2k in the invention recited by Application ‘984 because the copending Application does not recite a quantity of DMG-PEG2k to be used, which would motivate one of ordinary skill to use the quantity taught by Lou.
Claims 1-2, 6, 10-11, 15-18, 20-25, 27-31, and 60 are directed to an invention not patentably distinct from claims 1-2, 6, 13, 15, 17, 28, 34, and 54 of commonly assigned copending Application No. 18/693,984 in view of Green 3 and Lou. Specifically, see above.
The U.S. Patent and Trademark Office may not institute a derivation proceeding in the absence of a timely filed petition. The USPTO normally will not institute a derivation proceeding between applications or a patent and an application having common ownership (see 37 CFR 42.411). Commonly assigned copending Application No. 18/693,984, discussed above, may form the basis for a rejection of the noted claims under 35 U.S.C. 102 or 103 if the commonly assigned case qualifies as prior art under 35 U.S.C. 102(a)(2) and the patentably indistinct inventions were not commonly owned or deemed to be commonly owned not later than the effective filing date under 35 U.S.C. 100(i) of the claimed invention.
In order for the examiner to resolve this issue the applicant or patent owner can provide a statement under 35 U.S.C. 102(b)(2)(C) and 37 CFR 1.104(c)(4)(i) to the effect that the subject matter and the claimed invention, not later than the effective filing date of the claimed invention, were owned by the same person or subject to an obligation of assignment to the same person. Alternatively, the applicant or patent owner can provide a statement under 35 U.S.C. 102(c) and 37 CFR 1.104(c)(4)(ii) to the effect that the subject matter was developed and the claimed invention was made by or on behalf of one or more parties to a joint research agreement that was in effect on or before the effective filing date of the claimed invention, and the claimed invention was made as a result of activities undertaken within the scope of the joint research agreement; the application must also be amended to disclose the names of the parties to the joint research agreement.
A showing that the inventions were commonly owned or deemed to be commonly owned not later than the effective filing date under 35 U.S.C. 100(i) of the claimed invention will preclude a rejection under 35 U.S.C. 102 or 103 based upon the commonly assigned case. Alternatively, applicant may take action to amend or cancel claims such that the applications, or the patent and the application, no longer contain claims directed to patentably indistinct inventions.
Claims 1-2, 6, 10-11, 15-18, 20-25, 27-31, and 60 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4-6, 8-10, 13-15, 17, and 28 of copending Application No. 18/246,063 in view of Green 3 (U.S. Patent No. 11,401,380 B2, priority to 28 March 2016), Lou (J. Control. Rel. 2020, 325, 370., provided by Applicant in the IDS filed on 7 May 2024), Green (WIPO International Patent Publication No. WO 2020/077159 A1, published on 16 April 2020, provided by Applicant in the IDS filed on 7 May 2024), and Selvaraj (J. Vaccines Vaccin. 2015, 6 (4), 1000292.).
This is a provisional nonstatutory double patenting rejection.
Copending Application No. 18/246,063 recites a composition and nanoparticle of formula (I), which is a PBAE polymer backbone identical to that recited in instant claim 1, wherein the PBAE polymer may have substituents B7, Sc12, and S90, may have an end-cap E63, and encapsulates mRNA (claims 1, 4-6, 8-9, 15, and 17). In some embodiments, the ratio of Sc12 and S90 is 15-80% (claim 10). Application ‘063 recites the composition to further comprise a PEG-lipid in an amount from 0-15% (claims 13-14) and a kit comprising the nanoparticle and composition of claim 1 (claim 28).
Copending Application No. 18/246,063 does not recite the amount of the nanoparticle by weight represented by the PBAE polymer, the PEG-lipid to be DMG-PEG2k, the zeta-potential of the nanoparticles, the polydispersity of a solution comprising the nanoparticles, the mRNA to be a self-amplifying mRNA (SAM) that encodes a rabies virus glycoprotein, the weight ratio of the PBAE polymer to the mRNA, nor the nanoparticle to comprise MgCl2. These deficiencies are offset by the teachings of Green 3, Lou, Green, and Selvaraj.
Green 3, Lou, Green, and Selvaraj have been described above.
Instant claims 1-2, 6, 10-11, 15-18, 20-25, 27-31, and 60 are obvious variations of copending Application No. 18/264,063 because it would have been prima facie obvious to a person of ordinary skill in the art at the time of filing to modify the nanoparticle recited by Application ‘063 to use the amount of PBAE polymer in the nanoparticle taught by Green 3, to use DMG-PEG2000 as the PEG-lipid, the polydispersity of a solution comprising the nanoparticles, the zeta-potential of the nanoparticles, and RVG-SAM taught by Lou, to use the weight ratio of the PBAE polymer to the mRNA taught by Green, and to comprise MgCl2 as taught by Selvaraj.
One of ordinary skill would be motivated to formulate their nanoparticle to comprise ~85% by weight PBAE polymer in view of the teachings of Green 3 because Application ‘063 does not teach an amount of polymer to be used in their nanoparticle and Green 3 provides information the ordinary artisan would need to complete their invention. Further, Green 3 teaches that this weight is appropriate for a nanoparticle comprising polymers that is intended to encapsulate RNA, which the ordinary artisan would recognize as relevant to their invention.
In view of the teachings of Lou, one of ordinary skill in the art would be motivated to select the RVG-SAM as the RNA cargo because Lou teaches the nucleic acid to be capable of encoding RVG, the only target for neutralizing antibodies for rabies, and that they can be successfully and efficiently encapsulated in lipid NPs. The ordinary artisan would recognize the application of NP-encapsulated SAMs as vaccines in treating rabies and would be motivated to combine the RVG-SAM with the NP recited in Application ‘063. In addition, Lou teaches that lipid NPs that successfully and efficiently encapsulate RVG-SAM and deliver the mRNA vaccine to cells have polydispersity in the range of 0.13-0.24 and a zeta-potential of <5 mV. The ordinary artisan would desire their NPs to encapsulate and deliver the RVG-SAM successfully and would therefore be motivated to formulate their nanoparticles to have those physicochemical characteristics. Further, the ordinary artisan would be motivated to select DMG-PEG2000 as the PEG-lipid in the invention recited by Application ‘923 because the copending Application recites the genus PEG-lipid but does not recite a specific species and Lou teaches DMG-PEG2000 to be suitable for use in a nanoparticle that encapsulates RNA for use as a vaccine.
In view of the teachings of Green, one of ordinary skill in the art would be motivated to formulate their nanoparticle with the PBAE polymers at a 30 w/w ratio with the RVG-SAM because Green teaches this ratio to be particularly effective at delivering encapsulated nucleic acid molecules to their targeted cells and an ordinary artisan would recognize this as desirable. A person of ordinary skill would desire optimal efficacy in an mRNA vaccine delivered via PBAE polymer nanoparticle and would therefore be motivated to use the 30 w/w ratio to pursue improved efficacy, particularly when Application ‘063 does not recite an appropriate ratio to be used. The ordinary artisan would also find it obvious to create a kit comprising the nanoparticle above because Green teaches it as a practical application of the nanoparticle.
Finally, in view of the teachings of Selvaraj, one of ordinary skill in the art would be motivated to modify the nanoparticles above to also comprise MgCl2 because Selvaraj teaches the excipient to provide stability to vaccines and to have the capability to enhance the immune response of subjects following administration. An ordinary artisan would desire their NP-encapsulated mRNA vaccine to be stable and have enhanced immunogenicity and would therefore be motivated to include MgCl2 in their nanoparticles. In addition, Selvaraj teaches that a rabies vaccine is compatible with MgCl2 and that immunogenicity was maintained in the presence of the salt, which would further motivate its inclusion.
Claims 1-2, 6, 10-11, 15-18, 20-25, 27-31, and 60 are directed to an invention not patentably distinct from claims 1, 4-6, 8-10, 13-15, 17, and 28 of commonly assigned copending Application No. 18/246,063 in view of Green 3, Lou, Green, and Selvaraj. Specifically, see above.
The U.S. Patent and Trademark Office may not institute a derivation proceeding in the absence of a timely filed petition. The USPTO normally will not institute a derivation proceeding between applications or a patent and an application having common ownership (see 37 CFR 42.411). Commonly assigned copending Application No. 18/246,063, discussed above, may form the basis for a rejection of the noted claims under 35 U.S.C. 102 or 103 if the commonly assigned case qualifies as prior art under 35 U.S.C. 102(a)(2) and the patentably indistinct inventions were not commonly owned or deemed to be commonly owned not later than the effective filing date under 35 U.S.C. 100(i) of the claimed invention.
In order for the examiner to resolve this issue the applicant or patent owner can provide a statement under 35 U.S.C. 102(b)(2)(C) and 37 CFR 1.104(c)(4)(i) to the effect that the subject matter and the claimed invention, not later than the effective filing date of the claimed invention, were owned by the same person or subject to an obligation of assignment to the same person. Alternatively, the applicant or patent owner can provide a statement under 35 U.S.C. 102(c) and 37 CFR 1.104(c)(4)(ii) to the effect that the subject matter was developed and the claimed invention was made by or on behalf of one or more parties to a joint research agreement that was in effect on or before the effective filing date of the claimed invention, and the claimed invention was made as a result of activities undertaken within the scope of the joint research agreement; the application must also be amended to disclose the names of the parties to the joint research agreement.
A showing that the inventions were commonly owned or deemed to be commonly owned not later than the effective filing date under 35 U.S.C. 100(i) of the claimed invention will preclude a rejection under 35 U.S.C. 102 or 103 based upon the commonly assigned case. Alternatively, applicant may take action to amend or cancel claims such that the applications, or the patent and the application, no longer contain claims directed to patentably indistinct inventions.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Sean J. Steinke, Ph.D., whose telephone number is (571) 272-3396. The examiner can normally be reached Mon. - Fri., 09:00 - 17:00 ET.
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, David Blanchard, can be reached at (571) 272-0827. 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.
/S.J.S./
Examiner, Art Unit 1619
/TIGABU KASSA/Primary Examiner, Art Unit 1619
Prosecution Insights