DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 11/7/2025 has been entered.
Claim Status
No amendments were filed. Claims 7-12 and 20 are withdrawn. Claims 1-6, 13-19, and 21-36 are currently under examination.
Election/Restrictions
Applicant’s election without traverse of I: SEQ ID NO: 1 for claim 1; II: 1,2-dioleoyloxy-3 (trimethylammonium)propane (DOTAP) as the cationic lipid for claim 17; III: squalene as the oil for claim 19; IV: capric triglyceride as the triglyceride for claim 20; V: gold as the high atomic number elements for claim 25; and VI. a phosphorous-terminated surfactant for claim 33 in the reply filed on 10/23/2024 is acknowledged.
Applicant has elected squalene as the oil for claim 19, therefore claim 20 reciting triglycerides is withdrawn.
Claims 7-12 and 20 and the non-elected inorganic particles in claims 25 and non-elected surfactants in claim 33 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10/23/2024.
Claim Rejections - 35 USC § 103 - maintained
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-6, 13-19, 21-22, and 26-30 are rejected under 35 U.S.C. 103 as being unpatentable over Erasmus et al. (A nanostructured lipid carrier for delivery of a replicating viral RNA provides single, low-dose protection against Zika. Molecular Therapy, 26(10), 2507-2522; published 10/03/2018) and Gale et al. (US20150017207A1; published 01/15/2015).
Erasmus’s disclosure is directed to compositions comprising replicating viral RNA and highly stable nanostructured lipid carriers (NLCs) (see abstract).
Regarding claims 1 and 4-6, Erasmus teaches compositions comprising RNA and nanoparticles comprising a hydrophobic liquid oil core, such as squalene, wherein lipids present in the hydrophobic core are in liquid phase at 25 degrees Celsius; and a hydrophilic surface with surfactants (p. 2508, left column, para 3; p. 2508, right column, para 4; p. 2514, right column, para 1; p. 2518, right column, para 2; and Figure 2).
However, Erasmus does not specifically teach the nucleic acid comprising a region encoding a sequence at least 85% identical to Applicant’s elected SEQ ID NO: 1.
Gale’s disclosure is directed to compositions and methods that enable activation of innate immune responses through RIG-I like receptor signaling (see abstract). Gale teaches that identifying pathogen-associated molecular patterns (PAMPs) that induce innate immune response can be useful to serve as anti-microbial therapeutics, such as adjuvants in combating or preventing infections, and to enhance the efficacy of more traditional vaccine therapeutics (see para 0006).
Regarding claims 1 and 4-6, Gale teaches a nucleic acid comprising a region encoding a sequence set forth in SEQ ID NO: 1 that is 100% identical to Applicant’s elected SEQ ID NO: 1 (see OA.Appendix mailed with non-final rejection on 12/6/24 for Sequence Alignment). Gale further teaches compositions comprising a nucleic acids and nanoparticles (see paras 0055-0057). Gale further teaches delivery systems that can include particle formulations, such as emulsions, microparticles, immune-stimulating complexes (ISCOMs), nanoparticles, which can be, for example, particles and/or matrices, and liposomes, and the like, which are advantageous for the delivery of antigens (see para 0057).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Erasmus’s composition of rvRNA and NLCs with a nucleic acid comprising the region encoding the nucleic acid set forth in SEQ ID NO: 1, as taught in Gale, because it would have amounted to a simple substitution of one known nucleic acid for another to obtain predictable results. One would have had a reasonable expectation of success because Erasmus and Gale are directed to pharmaceutical compositions comprising nucleic acids and nanoparticle delivery systems to modulate immune responses. Thus, the claimed invention as a whole is prima facie obvious.
Regarding claims 2 and 3, Gale teaches that the nucleic acid can comprise ssRNA or dsRNA (see para 0043).
Regarding claim 3, Erasmus teaches that the nucleic acid of rvRNA derived from the alphavirus genus (which are single-stranded RNA viruses) comprises a ssRNA (p. 2508, left column, paras 2-3).
Regarding claim 13, Erasmus teaches the nanoparticle characterized as having Z-average diameter ranging from 40 nm to 100 nm, as measured by dynamic light scattering, which includes the claimed limitation of “up to 100 nm” (see p. 2509, left column, para 1; p. 2511, right column, para 1; and Table 1).
Regarding claim 14, Erasmus teaches that the nucleic acid is complexed to the nanoparticle (see p. 2508, left column, para 3; entire document).
Regarding claims 15 and 17, Erasmus teaches that the hydrophilic surface further comprises the cationic lipid DOTAP (see p. 2509, left column, para 1; Table 1; and p. 2511, left column, para 3 through right column, para 1).
Regarding claim 16, Erasmus teaches N:P ratios for ng of cationic lipid to ng of rvRNA of 50 and 15 (see p. 2517, right column, para 2; Table 1; Figure 5; and p. 2519, left column, paras 2-3). Erasmus further teaches that the N:P ratios wherein the amount of the cationic lipid is measured based on positively charged nitrogen molar amount and the amount of the nucleic acid is measured based on negatively charged phosphate molar amount (p. 2509, left column, para 2).
Regarding claims 18-19, Erasmus teaches that the hydrophobic core comprises oil, such as squalene (p. 2508, left column, para 3; p. 2508, right column, para 4; p. 2514, right column, para 1; p. 2518, right column, para 2; and Figure 2). Erasmus further teaches that the oil is a triglyceride, such as Miglyol 810 (p. 2510, left column, para 2 through right column, para 1).
Regarding claim 21, Gale teaches that nanoparticles can comprise an inorganic particle (see para 0059).
Regarding claim 22, Gale teaches that the nanoparticle comprises aluminum salts, such as aluminum phosphate and aluminum hydroxide, which are metal salts, phosphates, and hydroxides, respectively (see para 0059).
Regarding claim 26, Erasmus teaches that the nanoparticle comprises surfactants (see p. 2508, right column, para 4; p. 2510, entire page).
Regarding claim 27, Erasmus teaches that the surfactant is a hydrophilic surfactant Tween (see p. 2508, right column, para 4). Erasmus further teaches hydrophobic sorbitan ester surfactants, or Spans, used for stabilizing NLCs (see p. 2517, left column, para 2).
Regarding claim 28, Erasmus teaches that the hydrophobic surfactant is Span 60 (sorbitan monostearate), Span 80 (sorbitan monooleate), or Span 85 (sorbitan trioleate) (see p. 2517, left column, para 2 and p. 2518, right column, para 2).
Regarding claim 29, Erasmus teaches that the hydrophilic surfactant is Tween 80, which is a polysorbate as defined in the instant specification in paragraph [0108] (see p. 2509, left column, para 2; Table 1; and p. 2518, right column, para 2).
Regarding claim 30, Gale teaches that pharmaceutical compositions can comprise phosphate-terminated lipids, such as monophosphoryl lipid (MPL) and a surfactant (see paras 0056-0058 and 0061).
Claims 23-25, 31-32, and 36 are rejected under 35 U.S.C. 103 as being unpatentable over Erasmus et al. (A nanostructured lipid carrier for delivery of a replicating viral RNA provides single, low-dose protection against Zika. Molecular Therapy, 26(10), 2507-2522; published 10/03/2018) and Gale et al. (US20150017207A1; published 01/15/2015) as applied to claims 1-6, 13-19, 21-22, and 26-30 above, and further in view Chen et al. (Nanochemistry and nanomedicine for nanoparticle-based diagnostics and therapy. Chemical reviews, 116(5), pp.2826-2885; published 01/22/2016).
The combined teachings of Erasmus and Gale are applied to claims 23-25, 31-32, and 36 as they are been applied to claims 1-6, 13-19, 21-22, and 26-30 in the 35 U.S.C. 103 discussion above. In particular, the combined teachings of Erasmus and Gale teach that the nanoparticle further comprises an inorganic particle (see discussion above re: claim 21).
However, Erasmus and Gale do not specifically teach that the inorganic particle comprises iron oxide, titanium dioxide, or silicon dioxide (claim 23), the inorganic particle comprises pure iron, magnetite, Fe3O4, manganese ferrite, or cobalt ferrite (claim 24), that the inorganic particle comprises a high atomic number element, wherein the high atomic number element is gold, silver, iodine, iron, gadolinium, platinum, bismuth, or combinations thereof (claim 25), that the phosphate-terminated lipid is trioctylphosphine oxide (TOPO) (claim 31), that the nanoparticle further comprises an inorganic particle, and wherein the inorganic particle is coated with a capping ligand and the surfactant (claim 32), and that the nucleic acid is present in an amount of about 10 or 12.5 pg (claim 36).
Chen’s disclosure is directed to a review of nanochemistry and nanomedicine for nanoparticle-based diagnostics and therapy comprising nucleic acids (see title; p. 2828, right column, para 1). Chen teaches organic and inorganic nanocarriers (Figure 2).
Regarding claim 23, Chen teaches that the inorganic particle can comprise iron oxide, titanium dioxide, or silicon dioxide (see p. 2832, left column, paras 2-3; p. 2840, left column, para 3; Table 1; Figure 4; and entire document).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the combined compositions of Erasmus and Gale comprising inorganic particles with the specific examples taught in Chen, because it would have amounted to simple combination of prior art elements of nanoparticle compositions according to known methods to yield predictable results. One would have had a reasonable expectation of success because Erasmus, Gale, and Chen are directed to compositions for nanoparticle delivery systems comprising nucleic acids. Thus, the claimed invention as a whole is prima facie obvious.
Regarding claim 24, Chen teaches the inorganic particle comprises pure iron, magnetite, Fe3O4, manganese ferrite, and cobalt ferrite (see p. 2832, left column, para 2 through right column, para 2; p. 2848, whole page; and Table 1).
Regarding claim 25, Chen teaches that the inorganic particle comprises a high atomic number element, wherein the high atomic number element is gold, silver, iodine, iron, gadolinium, platinum, bismuth, or combinations thereof (see p. 2831, whole page; p. 2832, left column, para 2 through right column, para 2; p. 2840, left column, paras 2-3; p. 2848, whole page; Figure 4; p. 2850, left column, para 2). Chen teaches that the different inorganic particles can be used in applications, such as X-ray CT bioimaging, because the large atomic weight elements serve as good CT contrast agents owing to their high X-ray absorption (see p. 2849, right column, paras 2-3).
Regarding claim 31, Chen teaches that the phosphate-terminated lipid is trioctylphosphine oxide (TOPO), which is a capping ligand (see p. 2867, right column, Quantum Dots; p. 2833, right column, para 3; Table 3; p. 2840, right column, para 1).
Regarding claim 32, Chen teaches that the inorganic particle is coated with a capping ligand (e.g., TOPO) and a surfactant (see p. 2867, right column, Quantum Dots; p. 2833, right column, para 3; Table 3; and p. 2840, right column, paras 1-2).
Regarding claim 36, Chen teaches that nucleic acid is present in an amount of 10 pg in a lateral flow immunochromatographic assay (see p. 2854, left column, para 1; Figure 20; and p. 2857, left column, para 2 through right column, para 3). In paragraph [0092] of the instant Specification, Applicant defines the term "about" in reference to a number or range of numbers “to mean the stated number and numbers +/-20% thereof, or 20% below the lower listed limit and 20% above the higher listed limit for the values listed for a range”. Accordingly, Chen teaches the range of 8-12 pg, which includes “about 12.5pg”.
Claims 33-35 are rejected under 35 U.S.C. 103 as being unpatentable over Erasmus et al. (A nanostructured lipid carrier for delivery of a replicating viral RNA provides single, low-dose protection against Zika. Molecular Therapy, 26(10), 2507-2522; published 10/03/2018) and Gale et al. (US20150017207A1; published 01/15/2015) as applied to claims 1-6, 13-19, 21-22, and 26-30 above, and further in view of Geall et al. (US20180085388A1; published 03/29/2018).
The combined teachings of Erasmus and Gale are applied to claims 33-35 as they are been applied to claims 1-6, 13-19, 21-22, and 26-30 in the 35 U.S.C. 103 discussion above.
However, Erasmus and Gale do not specifically teach that the surfactant is a phosphorous-terminated lipid (claim 33), that the surfactant is distearyl phosphatidic acid (DSPA) (claim 34), and that the composition is lyophilized (claim 35).
Geall’s disclosure is directed to delivery of RNA encoding an immunogen to trigger an immune response (see abstract). Geall further teaches delivering RNA to recognize the immune receptor RIG-1 (see paras 0005, 0012, and 0180).
Regarding claims 33-34, Geall teaches that the surfactant is a phosphorous-terminated lipid and is distearyl phosphatidic acid (DSPA) (see para 0036 and Table 1).
Regarding claim 35, Geall teaches that the composition is lyophilized (see paras 0030, 0160, and 0201). Geall further teaches that microparticle compositions have advantageous over liposomes because they can be lyophilized for stable storage (see para 0030).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the combined compositions of Erasmus and Gale by adding Geall’s DSPA surfactant, because it would have amounted to simple combination of prior art elements according to known methods to yield predictable results. It would have been further obvious to have lyophilized the microparticle compositions as disclosed in Geall because it would have amounted to simple combination of prior art elements according to known methods to yield predictable results. Furthermore, as discussed above, Geall teaches that microparticle compositions can be stored stably following lyophilization. One would have been motivated to lyophilize the compositions of Erasmus, Gale, and Geall for stable storage. One would have had a reasonable expectation of success because Erasmus, Gale, and Geall are directed to pharmaceutical compositions comprising nucleic acids and nanoparticle delivery systems. Thus, the claimed invention as a whole is prima facie obvious.
Response to Arguments
Applicant's arguments filed 11/7/2025 have been fully considered but they are not persuasive. Applicant argues against the Office’s position that one would have had a reasonable expectation of success because Erasmus and Gale are directed to pharmaceutical compositions comprising nucleic acids and nanoparticle delivery systems to modulate immune responses. Applicant argues that the cited combination of publications fails to provide a reasonable expectation of success for one of skill in the art to arrive at the claimed subject matter. Applicant, on page 1, argues that MPEP 2143.02 provides guidance to Examiners that an obviousness rejection requires "that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art." Further, the U.S. Court of Appeals for the Federal Circuit has made it clear that an obviousness determination requires finding both "that a skilled artisan would have been motivated to combine the teachings of the prior art ... and that the skilled artisan would have had a reasonable expectation of success in doing so." In re Stepan Co. 868 F.3d 1342, 1346 (Fed. Cir. 2017). Moreover, "If the proposed modification or combination of the prior art would change the principle of operation of the prior art invention being modified, then the teachings of the references are not sufficient to render the claims prima facie obvious. In re Ratti, 270 F.2d 810, 123 USPQ 349 (CCPA 1959)". Applicant argues that Erasmus, the disclosure provides express guidance away from such a carrier and a strong preference for an entirely different solution because Erasmus arrives at the solution of a nanoparticle having a mixed phase lipid inner core consisting of "a liquid oil phase, such as squalene, with a solid phase lipid composed of a saturated triglyceride." (Erasmus. at p. 2508, left column, para 3). Applicant further argues that Erasmus articulates clear shortcomings and concerns from use of a nanoparticle without a solid phase lipid in the core - establishing a lack of predictability for use of such constructs and that the solution proposed by Erasmus specifically teaches away from the present invention because the improvement in stability results from a lipid nanoparticle having a solid phase lipid in the core. Applicant argues, on pages 2-3, that Erasmus specifically stated stability benefit for the NLC composition from having a mixed phase lipid core including a solid phase lipid at p. 2508, right column, para 4.
Applicant argues that to arrive at the claimed subject matter based on the teachings of Erasmus, the skilled person would have to impermissibly apply hindsight reasoning and remove the solid phase lipid of the NLC, and therefore remove the specific development discussed therein and that there is no motivation from the disclosure of Erasmus to do this, and the entire purpose of Erasmus is to teach away from lipid nanoparticles where the lipids are all in a liquid phase. Applicant repeats the same arguments for rejections of claims 23-25, 31-32 and 36 over Erasmus, Gale, and Chen and of claims 33-35 over Erasmus, Gale, and Geall.
In response to applicant’s argument that there is no motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, the claimed invention is a composition comprising a liquid oil core and a nucleic acid (with 85% sequence identity to one of SEQ ID NOs: 1-11. Again, Erasmus teaches compositions comprising RNA and nanoparticles comprising a hydrophobic liquid oil core, such as squalene, wherein lipids present in the hydrophobic core are in liquid phase at 25 degrees Celsius; and a hydrophilic surface with surfactants and further teaches compositions comprising NLCs and the nucleic acid encoding secreted alkaline phosphatase. Dale teaches a nucleic acid having 100% identity to SEQ ID NO: 1. Therefore, as detailed in the 103 rejection above, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Erasmus’s composition of rvRNA and NLCs with a nucleic acid comprising the region encoding the nucleic acid set forth in SEQ ID NO: 1, as taught in Gale, because it would have amounted to a simple substitution of one known nucleic acid for another to obtain predictable results. The only difference is the nucleic acid sequence. Therefore, one would have had a reasonable expectation of success because both references teach pharmaceutical compositions comprising nucleic acids and nanoparticle delivery systems to modulate immune responses. Thus, the claimed invention as a whole is prima facie obvious.
The Office disagrees with Applicant’s argument that Erasmus teaches away from the claimed composition. The Office relies on Erasmus to teach the lipid nanoparticle formulation for the composition of claim 1 with a nucleic acid for a number of pharmaceutical uses including therapeutics, such a vaccine, as taught in Erasmus. One of ordinary skill in the art, however, would have recognized the advances in optimizing nucleic acid-LNP compositions for purposes other than strictly vaccines. Thus, one would not have been discouraged from arriving at the claimed invention.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). In the instant case, Erasmus teaches the claimed nanoparticle composition with a hydrophobic core and hydrophilic surface and Dale teaches the claimed nucleic acid, as discussed in the 103 rejection above.
Therefore the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date.
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 1-6, 13-19, and 26-30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 7, 9, and 14-15 of U.S. Patent No. US11141377B2 in view of Gale et al. (US20150017207A1; published 01/15/2015) and Erasmus et al. (A nanostructured lipid carrier for delivery of a replicating viral RNA provides single, low-dose protection against Zika. Molecular Therapy, 26(10), 2507-2522; published 10/03/2018).
Claims 1-3, 7, 9, and 14-15 of U.S. Patent No. US11141377B2 encompasses a composition comprising a nanoparticle, wherein the nanoparticle comprises: a hydrophobic core, wherein lipids present in the hydrophobic core are in liquid phase at 25 degrees Celsius; and a hydrophilic surface; and a nucleic acid and further comprises RIG-I agonist (encoded by Applicant’s elected species of SEQ ID NO: 1). Claims 1-3, 7, 9, and 14-15 of U.S. Patent No. US11141377B2 teach an oil core comprising a mixture of a liquid phase lipid and a solid phase lipid, wherein the liquid phase lipid is squalene and the solid phase lipid is trimyristin (triglyceride), a cationic component that is DOTAP, a hydrophobic surfactant that is sorbitan monostearate, a hydrophilic surfactant that is polysorbate; and that the nucleic acid is RNA, which is single-stranded or double-stranded. Claims 1-3, 7, 9, and 14-15 of U.S. Patent No. US11141377B2 further teach that the z-average diameter of the NLC particles is from about 40 nm to about 80 nm, which covers the recited range of “up to 100 nm”.
However, claims 1-3, 7, 9, and 14-15 of U.S. Patent No. US11141377B2 do not specifically teach the nucleic acid comprising a region encoding a sequence that is at least 85%, 90%, 95% or 100% identical to Applicant’s elected SEQ ID NO: 1 (claims 1 and 4-6), wherein a ratio of amount of the cationic lipid to amount of the nucleic acid is up to about 100:1, and wherein the amount of the cationic lipid is measured based on positively charged nitrogen molar amount and the amount of the nucleic acid is measured based on negatively charged phosphate molar amount (claim 16).
The teachings of Gale and Erasmus are discussed above. In particular, the teachings of Gale regarding the teaching Applicant’s elected SEQ ID NO: 1 (claims 1 and 4-6) and Erasmus regarding the ratio of amount of the cationic lipid to amount of the nucleic acid is up to about 100:1, and wherein the amount of the cationic lipid is measured based on positively charged nitrogen molar amount and the amount of the nucleic acid is measured based on negatively charged phosphate molar amount (claim 16) are discussed above.
It would have been obvious to one of ordinary skill in the art to have modified the nanoparticle compositions of claims 1-3, 7, 9, and 14-15 of U.S. Patent No. US11141377B2 with a nucleic acid comprising the region encoding the nucleic acid set forth in SEQ ID NO: 1, as taught in Gale, because it would have amounted to a simple substitution of one known nucleic acid for another to obtain predictable results. It would have been further obvious to have modified the nanoparticle compositions of claims 1-3, 7, 9, and 14-15 of U.S. Patent No. US11141377B2 with Erasmus’s 100:1 ratio of amount of the cationic lipid to amount of the nucleic acid because it would have amounted to simple combination of prior art elements of nanoparticle compositions according to known methods to yield predictable results. One would have had a reasonable expectation of success because U.S. Patent No. US11141377B2, Gale, and Erasmus are directed to pharmaceutical compositions comprising nucleic acids and nanoparticle delivery systems to modulate immune responses.
Claims 1-6, 13-19, and 21-30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 11-25, and 27-30 of U.S. Patent No. US11896677B2 in view of Gale et al. (US20150017207A1; published 01/15/2015) and Erasmus et al. (A nanostructured lipid carrier for delivery of a replicating viral RNA provides single, low-dose protection against Zika. Molecular Therapy, 26(10), 2507-2522; published 10/03/2018).
Claims 1-4, 11-25, and 27-30 of U.S. Patent No. US11896677B2 encompasses a composition comprising a nanoparticle, wherein the nanoparticle comprises: a hydrophobic core, wherein lipids present in the hydrophobic core are in liquid phase at 25 degrees Celsius; and a hydrophilic surface; and a nucleic acid encoding for a protein region and further comprises RIG-I agonist (encoded by Applicant’s elected species of SEQ ID NO: 1). Claims 1-4, 11-25, and 27-30 of U.S. Patent No. US11896677B2 teach the lipid nanoparticles comprise: squalene, sorbitan monostearate, and polysorbate 80, the solid phase lipid is trimyristin (triglyceride), a cationic component that is DOTAP, a hydrophobic surfactant that is sorbitan monostearate, sorbitan monooleate, or sorbitan trioleate, a hydrophilic surfactant that is polysorbate; and that the nucleic acid is RNA, which is single-stranded or double-stranded. Claims 1-4, 11-25, and 27-30 of U.S. Patent No. US11896677B2 further teach that the z-average diameter of the lipid nanoparticles is from about 20 nm to about 60 nm, which covers the recited range of “up to 100 nm”. Claims 1-4, 11-25, and 27-30 of U.S. Patent No. US11896677B2 further teach that the hydrophobic core comprises a solid inorganic nanoparticle comprises metal salts, metal oxides (iron oxide), metal hydroxides, or metal phosphates and that the liquid oil is capric/caprylic triglyceride, vitamin E, lauroyl polyoxylglyceride, monoacylglycerol, sunflower oil, soybean oil, olive oil, or grapeseed oil.
However, claims 1-4, 11-25, and 27-30 of U.S. Patent No. US11896677B2 do not specifically teach the nucleic acid comprising a region encoding a sequence that is at least 85%, 90%, 95% or 100% identical to Applicant’s elected SEQ ID NO: 1 (claims 1 and 4-6), wherein a ratio of amount of the cationic lipid to amount of the nucleic acid is up to about 100:1, and wherein the amount of the cationic lipid is measured based on positively charged nitrogen molar amount and the amount of the nucleic acid is measured based on negatively charged phosphate molar amount (claim 16).
The teachings of Gale and Erasmus are discussed above. In particular, the teachings of Gale regarding the teaching Applicant’s elected SEQ ID NO: 1 (claims 1 and 4-6) and Erasmus regarding the ratio of amount of the cationic lipid to amount of the nucleic acid is up to about 100:1, and wherein the amount of the cationic lipid is measured based on positively charged nitrogen molar amount and the amount of the nucleic acid is measured based on negatively charged phosphate molar amount (claim 16) are discussed above.
It would have been obvious to one of ordinary skill in the art to have modified the nanoparticle compositions of claims 1-4, 11-25, and 27-30 of U.S. Patent No. US11896677B2 with a nucleic acid comprising the region encoding the nucleic acid set forth in SEQ ID NO: 1, as taught in Gale, because it would have amounted to a simple substitution of one known nucleic acid for another to obtain predictable results. It would have been further obvious to have modified the nanoparticle compositions of claims 1-4, 11-25, and 27-30 of U.S. Patent No. US11896677B2 with Erasmus’s 100:1 ratio of amount of the cationic lipid to amount of the nucleic acid because it would have amounted to simple combination of prior art elements of nanoparticle compositions according to known methods to yield predictable results. One would have had a reasonable expectation of success because U.S. Patent No. US11896677B2, Gale, and Erasmus are directed to pharmaceutical compositions comprising nucleic acids and nanoparticle delivery systems to modulate immune responses.
Claims 1-6, 13-19, and 21-30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 and 7-28 of U.S. Patent No. US11318213B2 in view of Gale et al. (US20150017207A1; published 01/15/2015) and Erasmus et al. (A nanostructured lipid carrier for delivery of a replicating viral RNA provides single, low-dose protection against Zika. Molecular Therapy, 26(10), 2507-2522; published 10/03/2018).
Claims 1-3 and 7-28 of U.S. Patent No. US11318213B2 encompasses a nanoparticle emulsion composition, wherein the nanoparticle comprises: hydrophobic core comprising a mixture of a liquid oil and a solid inorganic nanoparticle; a cationic lipid; a hydrophilic surfactant; a hydrophobic surfactant; and a nucleic acid, wherein the nucleic acid modulates innate immune response and is complexed with the nanoparticles and further comprises RIG-I agonist (encoded by Applicant’s elected species of SEQ ID NO: 1). Claims 1-3 and 7-28 of U.S. Patent No. US11318213B2 teach the lipid nanoparticles comprise: a cationic component that is DOTAP, a hydrophobic surfactant that is sorbitan monostearate, sorbitan monooleate, or sorbitan trioleate, a hydrophilic surfactant that is polysorbate; and that the nucleic acid is RNA, which is single-stranded or double-stranded. Claims 1-3 and 7-28 of U.S. Patent No. US11318213B2 further teach that the z-average diameter of the lipid nanoparticles is from about 40 nm to about 200 nm, which covers more than the recited range of “up to 100 nm”. Claims 1-3 and 7-28 of U.S. Patent No. US11318213B2 further teach that solid inorganic nanoparticle can be metal salts, metal oxides (iron oxide), metal hydroxides, or metal phosphates and that the liquid oil is capric/caprylic triglyceride, vitamin E, lauroyl polyoxylglyceride, monoacylglycerol, sunflower oil, soybean oil, olive oil, or grapeseed oil.
However, claims 1-3 and 7-28 of U.S. Patent No. US11318213B2 do not specifically teach the nucleic acid comprising a region encoding a sequence that is at least 85%, 90%, 95% or 100% identical to Applicant’s elected SEQ ID NO: 1 (claims 1 and 4-6), wherein a ratio of amount of the cationic lipid to amount of the nucleic acid is up to about 100:1, and wherein the amount of the cationic lipid is measured based on positively charged nitrogen molar amount and the amount of the nucleic acid is measured based on negatively charged phosphate molar amount (claim 16).
The teachings of Gale and Erasmus are discussed above. In particular, the teachings of Gale regarding the teaching Applicant’s elected SEQ ID NO: 1 (claims 1 and 4-6) and Erasmus regarding the ratio of amount of the cationic lipid to amount of the nucleic acid is up to about 100:1, and wherein the amount of the cationic lipid is measured based on positively charged nitrogen molar amount and the amount of the nucleic acid is measured based on negatively charged phosphate molar amount (claim 16) are discussed above.
It would have been obvious to one of ordinary skill in the art to have modified the nanoparticle compositions of claims 1-3 and 7-28 of U.S. Patent No. US11318213B2 with a nucleic acid comprising the region encoding the nucleic acid set forth in SEQ ID NO: 1, as taught in Gale, because it would have amounted to a simple substitution of one known nucleic acid for another to obtain predictable results. It would have been further obvious to have modified the nanoparticle compositions of claims 1-3 and 7-28 of U.S. Patent No. US11318213B2 with Erasmus’s 100:1 ratio of amount of the cationic lipid to amount of the nucleic acid because it would have amounted to simple combination of prior art elements of nanoparticle compositions according to known methods to yield predictable results. One would have had a reasonable expectation of success because U.S. Patent No. US11318213B2, Gale, and Erasmus are directed to pharmaceutical compositions comprising nucleic acids and nanoparticle delivery systems to modulate immune responses.
Claims 1-6, 13-19, and 21-30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 20-23, 26, and 28-43 of U.S. Patent No. US11654200B2 in view of Gale et al. (US20150017207A1; published 01/15/2015).
Claims 1-3, 20-23, 26, and 28-43 of U.S. Patent No. US11654200B2 encompasses a method for delivering compositions of nucleic acids comprising a nanoparticle, wherein the nanoparticle comprises: a hydrophobic core, wherein lipids present in the hydrophobic core are in liquid phase at 25 degrees Celsius; and a hydrophilic surface; and the z-average diameter of the lipid nanoparticles is from about 20 nm to about 60 nm, which covers the recited range of “up to 100 nm”. Claims 1-3, 20-23, 26, and 28-43 of U.S. Patent No. US11654200B2 further teaches that the nucleic acids comprise a RIG-I agonist (encoded by Applicant’s elected species of SEQ ID NO: 1). Claims 1-3, 20-23, 26, and 28-43 of U.S. Patent No. US11654200B2 teach the lipid nanoparticles comprise: squalene, sorbitan monostearate, and polysorbate 80, the solid phase lipid is trimyristin (triglyceride), a cationic component that is DOTAP, a hydrophobic surfactant that is sorbitan monostearate, sorbitan monooleate, or sorbitan trioleate, a hydrophilic surfactant that is polysorbate; and that the nucleic acid is RNA, which is single-stranded or double-stranded. Claims 1-3, 20-23, 26, and 28-43 of U.S. Patent No. US11654200B2 further teach that the hydrophobic core comprises a solid inorganic nanoparticle comprises metal salts, metal oxides (iron oxide), metal hydroxides, or metal phosphates and that the liquid oil is capric/caprylic triglyceride, vitamin E, lauroyl polyoxylglyceride, monoacylglycerol, sunflower oil, soybean oil, olive oil, or grapeseed oil.
However, claims 1-3, 20-23, 26, and 28-43 of U.S. Patent No. US11654200B2 do not specifically teach the nucleic acid comprising a region encoding a sequence that is at least 85%, 90%, 95% or 100% identical to Applicant’s elected SEQ ID NO: 1 (claims 1 and 4-6).
The teachings of Gale are discussed above. In particular, the teachings of Gale regarding the teaching Applicant’s elected SEQ ID NO: 1 (claims 1 and 4-6).
It would have been obvious to one of ordinary skill in the art to have modified the nanoparticle compositions of claims 1-3, 20-23, 26, and 28-43 of U.S. Patent No. US11654200B2 with a nucleic acid comprising the region encoding the nucleic acid set forth in SEQ ID NO: 1, as taught in Gale, because it would have amounted to a simple substitution of one known RIG-1 agonist nucleic acid for another to obtain predictable results. One would have had a reasonable expectation of success because U.S. Patent No. US11654200B2 and Gale are directed to pharmaceutical compositions comprising nucleic acids and nanoparticle delivery systems to modulate immune responses.
Claims 1-6, 13-19, and 21-30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-13, and 17-30 of copending Application No. 17/523442 in view of Gale et al. (US20150017207A1; published 01/15/2015) and Erasmus et al. (A nanostructured lipid carrier for delivery of a replicating viral RNA provides single, low-dose protection against Zika. Molecular Therapy, 26(10), 2507-2522; published 10/03/2018).
Claims 1, 3-13, and 17-30 of the ‘442 application encompass nanoparticle compositions comprising a hydrophobic core, with a mixture of liquid oil and a solid inorganic nanoparticle, a cationic lipid, a hydrophobic surfactant and a hydrophilic surfactant. Claims 1, 3-13, and 17-30 of the ‘442 further teach the liquid oil is squalene, the cationic component lipid is DOTAP, a hydrophobic surfactant that is sorbitan monostearate, a hydrophilic surfactant that is polysorbate; and that the nucleic acid is RNA, which is single-stranded or double-stranded. Claims 1, 3-13, and 17-30 of the ‘442 further teach that the z-average diameter of the NLC particles is from about 40 nm to about 80 nm, which covers the recited range of “up to 100 nm”. Claims 1, 3-13, and 17-30 of the ‘442 further teach the solid inorganic nanoparticle comprises iron oxide and the liquid oil is capric/caprylic triglyceride, vitamin E, lauroyl polyoxylglyceride, monoacylglycerol, squalene, squalane, or any combination thereof,
However, the copending claims do not specifically teach the nucleic acid comprising a region encoding a sequence that is at least 85%, 90%, 95% or 100% identical to Applicant’s elected SEQ ID NO: 1 (claims 1 and 4-6), wherein a ratio of amount of the cationic lipid to amount of the nucleic acid is up to about 100:1, and wherein the amount of the cationic lipid is measured based on positively charged nitrogen molar amount and the amount of the nucleic acid is measured based on negatively charged phosphate molar amount (claim 16).
The teachings of Gale and Erasmus are discussed above. In particular, the teachings of Gale regarding the teaching Applicant’s elected SEQ ID NO: 1 (claims 1 and 4-6) and Erasmus regarding the ratio of amount of the cationic lipid to amount of the nucleic acid is up to about 100:1, and wherein the amount of the cationic lipid is measured based on positively charged nitrogen molar amount and the amount of the nucleic acid is measured based on negatively charged phosphate molar amount (claim 16) are discussed above.
It would have been obvious to one of ordinary skill in the art to have modified the nanoparticle compositions of claims 1, 3-13, and 17-30 of the ‘442 application with a nucleic acid comprising the region encoding the nucleic acid set forth in SEQ ID NO: 1, as taught in Gale, because it would have amounted to a simple combination of prior art elements of nanoparticle compositions according to known methods to yield predictable results. It would have been further obvious to have modified the nanoparticle compositions of claims 1, 3-13, and 17-30 of the ‘442 application with Erasmus’s 100:1 ratio of amount of the cationic lipid to amount of the nucleic acid because it would have amounted to a simple combination of prior art elements of nanoparticle compositions according to known methods to yield predictable results. One would have had a reasonable expectation of success because the claims of the copending claims, Gale, and Erasmus are directed to pharmaceutical compositions comprising nucleic acids and nanoparticle delivery systems.
This is a provisional nonstatutory double patenting rejection.
Claims 1-6, 13-19, and 26-30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 5, 43, 45, 140-143, 153-154, and 156 of copending Application No. 17/470874 in view of Gale et al. (US20150017207A1; published 01/15/2015) and Erasmus et al. (A nanostructured lipid carrier for delivery of a replicating viral RNA provides single, low-dose protection against Zika. Molecular Therapy, 26(10), 2507-2522; published 10/03/2018).
Claims 1-2, 5, 43, 45, 140-143, 153-154, and 156 of the ‘874 application encompass a composition comprising a nanoparticle, wherein the nanoparticle comprises: a hydrophobic core, wherein lipids present in the hydrophobic core are in liquid phase at 25 degrees Celsius; and a hydrophilic surface; and a nucleic acid and further comprises an adjuvant that can be RNA. Claims 1-2, 5, 43, 45, 140-143, 153-154, and 156 of the ‘874 further teach an oil core comprising a mixture of a liquid phase lipid and a solid phase lipid, wherein the liquid phase lipid is squalene and the solid phase lipid is trimyristin (triglyceride), a cationic component that is DOTAP, a hydrophobic surfactant that is sorbitan monostearate, a hydrophilic surfactant that is polysorbate; and that the nucleic acid is RNA, which is single-stranded or double-stranded. Claims 1-2, 5, 43, 45, 140-143, 153-154, and 156 of the ‘874 further teach that the z-average diameter of the NLC particles is from about 40 nm to about 80 nm, which covers the recited range of up to 100 nm.
However, the copending claims do not specifically teach the nucleic acid comprising a region encoding a sequence that is at least 85%, 90%, 95% or 100% identical to Applicant’s elected SEQ ID NO: 1 (claims 1 and 4-6), wherein a ratio of amount of the cationic lipid to amount of the nucleic acid is up to about 100:1, and wherein the amount of the cationic lipid is measured based on positively charged nitrogen molar amount and the amount of the nucleic acid is measured based on negatively charged phosphate molar amount (claim 16).
The teachings of Gale and Erasmus are discussed above. In particular, the teachings of Gale regarding the teaching Applicant’s elected SEQ ID NO: 1 (claims 1 and 4-6) and Erasmus regarding the ratio of amount of the cationic lipid to amount of the nucleic acid is up to about 100:1, and wherein the amount of the cationic lipid is measured based on positively charged nitrogen molar amount and the amount of the nucleic acid is measured based on negatively charged phosphate molar amount (claim 16) are discussed above.
It would have been obvious to one of ordinary skill in the art to have modified the nanoparticle compositions of claims 1-2, 5, 43, 45, 140-143, 153-154, and 156 of the ‘874 application with a nucleic acid comprising the region encoding the nucleic acid set forth in SEQ ID NO: 1, as taught in Gale, because it would have amounted to a simple substitution of one known nucleic acid for another to obtain predictable results. It would have been further obvious to have modified the nanoparticle compositions of claims 1-2, 5, 43, 45, 140-143, 153-154, and 156 of the ‘874 application with Erasmus’s 100:1 ratio of amount of the cationic lipid to amount of the nucleic acid because it would have amounted to a simple combination of prior art elements of nanoparticle compositions according to known methods to yield predictable results. One would have had a reasonable expectation of success because the claims of the copending claims, Gale, and Erasmus are directed to pharmaceutical compositions comprising nucleic acids and nanoparticle delivery systems to modulate immune responses.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments filed 7/10/2025 have been fully considered but they are not persuasive.
Applicant argues that NSDP rejections of claims 1-3, 7, 9 and 14-15 of U.S. Patent No. 11,141,377 ("the '377 patent") in view of Gale and Erasmus and of claims 1-3 and 7-28 of U.S. Patent No. US11,318,213 ("the '213 patent") in view of Gale and Erasmus should be withdrawn because the patents require a liquid and solid lipid composition and argue that the present invention recites a complete liquid phase as recited in claim 1. The broadest reasonable interpretation of claim 1 of the present invention is of a composition that “comprises” a liquid phase, but does not specifically exclude a solid phase. Therefore, the rejections are maintained.
Applicant requests that the Office hold double patenting rejections of claims 1-4, 11-25 and 27-30 of U.S. Patent No. 11,896,677 ("the '677 patent") in view of Gale and Erasmus and of claims 1-3, 20-23, 26 and 28-43 of U.S. Patent No. 11,654,200 ("the '200 patent") in view of Gale in abeyance until an otherwise allowable set of claims has been agreed to by the Office, at which time Applicant will consider submitting a terminal disclaimer if so required. However, such a response is not a proper reply to the outstanding rejection of record.
Applicant argues that provisional NSDP rejections of claims 1-2, 5, 43, 45, 140-143, 153-154 and 156 of copending Application No. 17/470,874 ("the '874 application") in view of Gale and Erasmus. See above for arguments regarding the concept of a complete liquid core excluding a solid liquid phase.
Applicant requests that the Office hold provisional double patenting rejection of claims 1, 3-13 and 17-30 of copending Application No. 17/523,442 ("the '442 patent") in view of Gale and Erasmus in abeyance until an otherwise allowable set of claims has been agreed to by the Office, at which time Applicant will consider submitting a terminal disclaimer if so required. However, such a response is not a proper reply to the outstanding rejection of record.
Conclusion
No claim is allowed.
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/KHALEDA B HASAN/Examiner, Art Unit 1636
/BRIAN WHITEMAN/Primary Examiner, Art Unit 1636
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