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 .
Claim Status
Claims 1, 5, 6, 9-13, 15-17, 19, 21-25, 27, 28, and 30 are currently pending.
Claims 2-4, 7, 8, 14, 18, 20, 26, and 29 are cancelled.
Claims 1, 27, 28, and 30 are withdrawn.
Claims 5, 6, 9-13, 15-17, and 21-25 are being examined on the merits.
Election/Restriction
Applicant's election without traverse Group II (claims 5, 6, 9-13, 15-17, 19 and 21-25) with species election (a) squalene for the fusogenic oil; (b) Dlin-MC3-DMA for the ionizable lipids; (c) combination of DOPE and cholesterol for the neutral lipids; and (d) DMG-PEG200 for the PEGylated lipids. The claims encompassed by Group II have been adjusted in light of Applicant’s claim amendments, in the reply filed on March 13, 2026, is acknowledged.
Claims 1, 27, 28, and 30 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 March 13, 2026.
In addition, claims 1, 27, 28, and 30 withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim. Since the applicant elected the previously listed species, the above-mentioned claims are withdrawn.
The requirement is still deemed proper and is therefore made FINAL.
Information Disclosure Statement
The Information Disclosure Statement(s) submitted on April 22,2024 and November 06, 2025, are being considered by the Examiner.
Claim Objections
Claim 9 objected to because of the following informalities: “fusagenic” should read as “fusogenic”. Appropriate correction is required.
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.
Claim 12 is 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 12 recites “wherein the fusogenic oil comprises squalene, squalane, pristane, pristene, farnesene, farnesane, retinol, phytol, a carotene, a tocopherol, a tocotrienol, phytomenadione, menaquinone, where valence permits esters thereof, and combinations thereof ”, it is unclear if the fusogenic oil is meant to be selected from the group consisting of A, B, C, D, and combinations thereof, or if the claim should state comprises squalene….or combinations thereof where applicants intend the fusogenic oils to comprise at least one of the listed oils, or if applicant’s actually intended that the fusogenic oil comprises all of the oils collectively as the claim is currently plainly written? If applicants intend the fusogenic oils to be all of the oils collectively then it is also unclear why applicants are claiming the various combinations thereof of the fusogenic oils because the use of the word “and” to link the comprising group appears to signal that all of the oils are actually required but the presence of the combinations thereof appears to signal that applicants do not intend the fusogenic oils to comprise all of the oils at once or if the language as written is actually a typo and applicants intended the language to be one of other possibilities set forth above? Because the language of the claims appears to disagree with itself based on the multiple interpretations above, the metes and bounds of what applicant’s claim for their fusogenic oils is unclear to the examiner. For purposes of compact prosecution, based on applicant’s election and the instant specification, the claim is interpreted as comprising squalene…, or combinations thereof.
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 is currently called 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 5, 6, 9-13, 15-17, 19, 21-25 are rejected under 35 U.S.C 103 as being unpatentable over Mundus et al (US9238021B2; Published on January 19, 2016; filed on January 04, 2014) in view of Garcia et al (WO2014032953A1; Published on March 6, 2015, cited on IDS) and Jianxin et al (US20100324120A1; Published on December 23, 2010, cited on IDS) and Brito et al ( WO2012006380A2; Published on January 12, 2012)
Claim 5 is drawn to, a pharmaceutical composition comprising a lipid particle encapsulating an active agent, the lipid particle comprising: from 20 mol % to 65 mol % one or more ionizable lipids; from 35 mol % to 80 mol % one or more neutral lipids; from greater than 0 mol % to 10 mol % one or more PEGylated lipids; and from 5 mol % to 50 mol % one or more fusogenic oils.
With regards to claims 5, 6, 19, 23, and 24, Mundus et al throughout teaches a liposomal preparation comprising a lipophilic active compound and a cationic liposomal preparation.
For claims 5: Mundus teaches a pharmaceutical composition comprising any one of the inventive liposomal preparations together with a pharmaceutically acceptable carrier, (column 17, line 12). Mundus also teaches an active lipophilic compound that may be loaded (reads on encapsulating of the claim) into cationic liposomes (reads on particle of the claim) of the present invention. Mundus teaches cationic lipids(reads on ionizable lipid) of at least about 30 mol % (Mundus claim 1), amphiphile (reads on neutral lipid) of up to about 69.9 mol %, a lipophilic active compound of at least about 2 mol %, and a stabilizing agent of about 0.1% (m/v) (reads on pegylated lipids of the claim) (Mundus claim 1). Mundus further states that pegylated lipids such as 1,2-diacyl-sn-glycero-3-phosphoethanolamine, including but not limited to dioleoyl (DOPE), 1,2-diacyl-glycero-3-phosphocholines, which are known stabilizing agents (Mundus column 5, line 28). Mundus further teaches that the amphiphile may be selected from an amphiphile having a neutral or anionic net charge of its hydrophilic moiety (head group) (Mundus column 5, line 22).
For claim 6: Mundus discloses a buffer substance and a stabilizing agent that has a pH value between about 3 and 7, preferably between about 4 and about 6.5 (Mundus column 5, line 36).
For claim 19: Mundus further discloses that that the amphiphile is pegylated lipid such as cholesterol…,1,2-diacyl-sn-glycero-3-phosphoethanolamine, including but not limited to dioleoyl (DOPE) (Mundus column 5 line 28).
For claim 23: Mundus teaches liposomal preparation comprises liposomes with an average particle size of about 50 nm to about 400 nm (converts to 0.05 to 0.4 micron) (Mundus claim 16).
For claim 24: Mundus teaches PI-values (reads on polydispersity of the claim) of the inventive cationic liposomal preparation are below about 0.4 and most preferred below about 0.3 (Mundus column 8, line 59).
Mundus does not appear to explicitly teach fusogenic oils, as recited in claims 5 and 9-13. Mundus does not teach molar ratio of fusogenic oil to ionizable and PEGylated lipids, as recited in claims 17 and 22. Mundus also does not teach ionizable lipids with a tertiary amine, the type of ionizable, neutral, and PEGylated lipids, or that the active agent comprises a nucleic acid, as recited in claims 15, 16, 21, and 25. Garcia, Jianxin, and Brito references are relied upon for these disclosures. Their teachings are set forth herein below.
Garcia et al teaches a nanoemulsion formulation with a nucleotide sequence delivery system with an aqueous phase and dispersed phase.
For claims 5, 9, 10, and 11: Garcia teaches a formulation comprising from 15 to 70 mol% of cationic surfactant (reads on fusogenic lipid or oil) (Garcia claim 1). Garica later discloses that cationic surfactant is optional fusogenic lipid (claim 1) Garcia further discloses a linear or branched alkyl group comprising from 1 to 12 carbon atoms and interrupted and/or substituted by at least one cationic group (Garcia claim 1). Garcia also teaches that the composition comprises at least one poly (ethylene oxide) chain (reads on the alkylene of the claim) comprising at least 25 ethylene oxide units (Garcia claim 1).
Chen et al throughout teaches a cationic lipid of Dlin-MC3-DMA
For claims 15, 16, 17, 21, and 22: Chen teaches a lipid particle that consists essentially of (i) at least one lipid of the present invention; (ii) a neutral lipid selected from DSPC, DPPC, POPC, DOPE; (iii) sterol, e.g. cholesterol; and (iv) peg-lipid, e.g. PEG-DMG (reads on PEG-myristoly diglyceride of the claim) (Chen paragraph 0020). Chen further teaches a lipid particle consists of or consists essentially of DLin-M-C3-DMA (which has a tertiary amine head group), DSPC, Chol, and PEG-DMG (reads on PEG-myristoly diglyceride of the claim), in a molar ratio of about 20-60% DLin-M-C3-DMA: 5-25% DSPC :25-55% Chol:0.5-15% PEG-DMG. In particular embodiments, the molar lipid ratio is approximately 40/10/40/10 (mol % DLin-M-C3-DMA/DSPC/Chol/PEG-DMG) (Chen paragraph 0164). Chen further discloses in another group of embodiments, the neutral lipid, DSPC, in these compositions is replaced with DOPE (Chen paragraph 0164).
For claim 25: Chen discloses that the active agent be any type of molecule or compound, including e.g., nucleic acid (Chen claim 11).
Brito et al throughout teaches an emulsion particle that is comprised of an oil core and a cationic lipid.
For claims 12 and 13: Brito teaches cationic lipid comprising of an oil core comprising of… squalene (Brito paragraph 0026). Brito further discloses the cationic lipid DLinDMA (Brito paragraph 0028)
With regards to claims 5, 9, 10, 12-13, Mundus discloses liposomal preparation cationic lipids, as discussed above. Both Garica and Brito disclose a cationic lipid as discussed. One of ordinary skill in the art would have found it prima facie obvious before the effective filing date of the instant invention to combine the teachings of Mundus, Garcia, and Brito by incorporating fusogenic lipid such as squalene into the liposomal preparation taught by Garcia. One ordinary skill in the art would have been motivated to do so for because fusogenic oils such as squalene are known for endosomal release . One of ordinary skill in the art would have had a reasonable expectation of success in doing so because both Garcia and Brito teach the incorporation of fusogenic oils in cationic lipids.
With regards to lipid characteristics (claims 15, 16, 17, 21, and 25) Mundus teaches liposomal preparation cationic lipids as discussed above. Chen exemplifies a lipid particle that consists essentially of (i) at least one lipid of the present invention; (ii) a neutral lipid selected from DOPE; (iii) sterol, e.g. cholesterol; and (iv) PEG-lipid, e.g. PEG-DMG. One ordinary skill in the art would have found it prima facie obvious before the effective filing date of the instant invention to further combine the teachings of Mundus, Garcia, and Brito discussed above with the teachings of Chen and add the specific lipids such as DLin-M-C3-DMA, DOPE, cholesterol, PEG-DMG with a nucleic acid as the active agent at desired amounts, such as 40/10/40/10 (mol % DLin-M-C3-DMA/DSPC/Chol/PEG-DMG) into the liposomal composition of the combined teachings of Mundus, Garcia, and Brito. One of ordinary skill in the art would have been motivated to do so for improvement of RNA-based formulations susceptibility to nuclease digestion in plasma as disclosed. One of ordinary skill in the art would have had a reasonable expectation of success in doing so because Mundus and Chen teach cationic liposomal compositions.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, because the combined teachings of the prior art references is fairly suggestive of the claimed invention.
Conclusion
Claims 5, 6, 9-13, 15-17, 19, 21-25 are rejected. No claims are allowed.
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/J.A.E./ Examiner, Art Unit 1616
/ERIN E HIRT/ Primary Examiner, Art Unit 1616
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