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 .
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.
Election/Restrictions
Applicant's election with traverse of Group I, claims 25-42 and the species election of W21.7 as the imidazolium-based cationic lipid of formula (I) and mRNA as the nucleic acid in the reply filed on 09/28/2026 is acknowledged.
The traversal is on the ground(s) that the claims of the identified groups are related as a product and process of use of said product and therefore have unity of invention.
The Examiner disagrees. Groups I-V lack unity of invention because even though the inventions of these groups require the technical features of a nucleic acid and a lipid nanoparticle comprising an ionizable lipid, a phospholipid, a sterol, a PEG-lipid, and an imidazolium-based cationic lipid of formula (I), these technical features are not special technical features as they do not make a contribution over the prior art in view of Hennessy et al. (US 2022/0047518 A1) and Stock (WO 2020/089342 A1) (see pg. 5-6 of restriction requirement). Groups I-V lack unity of invention, and do not make a contribution to the art, in view of Hennessy and Stock.
The requirement is still deemed proper and is therefore made FINAL.
Claims 43-50 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claim Objections
Claims 25, 27, 29, 31, 33, and 35 are objected to because of the following informalities:
Claim 25, line 15 reads “linear or branched hydrocarbon chain selected among” and should read “linear or branched hydrocarbon chain selected from
In claim 27 names of compounds are unnecessarily capitalized such as Heptadecan-9-yl 8-{(2- hydroxyethyl)[6-oxo-6-(undecyloxy)hexyl]amino Ioctanoate and [(4- Hydroxybutyl)azanediyl]di(hexane-6,1-diyl) bis(2-hexyldecanoate).
In claim 29 names of compounds are unnecessarily capitalized, such as 1,2-Dioleoyl-sn-glycero-3-phosphoethanolamine.
In claim 31 “1” is listed as a sterol in line 2 and should be deleted.
In claim 33 names of compounds are unnecessarily capitalized, such as 1,2-Dimyristoyl-sn-glycero-3-methoxypolyethylene glycol and 1,2-Distearoyl-rac-glycero-3-methylpolyoxyethylene.
Claim 35 requires a period at the end of the claim. See MPEP 608.01(m).
Appropriate correction is required.
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 25-42 are rejected under 35 U.S.C. 103 as being as being obvious over Karve et al. (US 2021/0353556 A1) in view of Stock et al. (WO 2020/089342 A1).
Regarding claim 25, Karve discloses a composition comprising mRNA-loaded lipid nanoparticles for mRNA delivery in therapeutic use [abstract] [0004] where the lipid nanoparticles include a cationic lipid (e.g., MC-3; known synonym in the art for DLin-MC3-DMA), a non-cationic lipid (e.g., DSPC or DOPE), a cholesterol-based lipid (e.g., cholesterol) and a PEG-modified lipid (e.g., DMG - PEG2K) [0234] [0316]-[0341]. The nucleic acid is encapsulated in the lipid nanoparticle [0031] [0316]-[0341].
Karve does not disclose an imidazolium-based cationic lipid of formula (I).
Stock discloses a composition comprising mRNA, at least one neutral lipid (such as DOPE, pg. 11, lines 18-19; pg. 73-75), and a cationic lipid of formula (I) (abstract). Compound W21.7 is disclosed as a preferred compound of formula (I) (pg. 16, bottom - pg. 17, top).
PNG
media_image1.png
365
615
media_image1.png
Greyscale
Stock teaches that the composition with the cationic lipid is able to interact with cell membranes (pg. 8, lines 8-10) and that the neutral lipid and cationic lipid are efficient in transfecting mRNA into a cell (pg. 20, lines 19-20; pg. 73-75).
Since Karve generally teaches a lipid formulation for the delivery of mRNA with neutral lipids, such as DOPE, it would have been prima facie obvious to one of ordinary skill in the art to include a cationic lipid of formula (I), such as W21.7, within the teachings of Karve, because Stock teaches W21.7 as a preferred cationic lipid to be used in combination with a neutral lipid (such as DOPE) in a lipid formulation for the delivery of mRNA. An ordinarily skilled artisan would have been motivated to use a cationic lipid, such as W21.7, because Stock teaches that the composition with the cationic lipid is able to interact with cell membranes (pg. 8, lines 8-10) and that the combination of the neutral lipid and cationic lipid is efficient in transfecting mRNA into a cell (pg. 20, lines 19-20; pg. 73-75).
Claims 26 and 41 are rendered prima facie obvious because Karve discloses mRNA is loaded in the lipid nanoparticles [abstract] [0004].
Claims 27, 29, 31, and 33 are rendered prima facie obvious because Karve discloses the lipid nanoparticles include a cationic lipid (e.g., MC-3; known synonym in the art for DLin-MC3-DMA), a non-cationic lipid (e.g., DSPC or DOPE), a cholesterol-based lipid (e.g., cholesterol) and a PEG-modified lipid (e.g., DMG - PEG2K) [0234] [0316]-[0341].
Claims 28, 30, 32, and 34 are rendered prima facie obvious because Karve discloses, the molar ratio of cationic lipid(s) (e.g., MC-3) to non-cationic lipid(s) (e.g. DSPC or DOPE) to cholesterol-based lipid(s) to PEG-modified lipid(s) in the LNPs may be between about 35-55:5-35:20-40:1-15, respectively. In particular embodiments, the molar ratio of cationic lipid(s) (e.g. MC-3) to non-cationic lipid(s) (e.g. DSPC or DOPE) to cholesterol-based lipid(s) to PEG-modified lipid(s) in the LNPs is about 50:10:35:5 [0234] [0316]-[0341]. In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. See MPEP 2144.05 A.
Regarding claims 35-36, and 42, while Karve does not disclose compound W21.7, it would have been prima facie obvious to include W21.7, as taught by Stock, within the teachings of Karve, as previously discussed.
Regarding claim 37, Karve does not disclose from 5 mole % to 40 mole % of the imidazolium-based cationic lipid.
However, the amount of the imidazolium-based cationic lipid would have been a matter of routine experimentation within the combined teachings of the prior art.
Karve discloses that the amount of non-cationic lipid (such as DOPE) to be used in the lipid nanoparticle formulation is between about 5-35 mol % [0234] [0316]-[0341].
Stock teaches that the molar ratio of the cationic lipid of formula (I) to the at least one neutral lipid (such as DOPE, pg. 11, lines 18-19; pg. 73-75) ranges from 1:1 to 1:2 (pg. 17, lines 13-14) and the composition is efficient in transfecting mRNA into a cell in this range (pg. 73-75). Furthermore, Stock teaches that the ratio of cationic lipids and neutral lipids in the composition modulates the surface charge density of the composition (pg. 8, lines 11-13).
Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. See MPEP 2144.05(II)(A). In this case, the general conditions of the amount/ratio of neutral lipid and cationic lipid of formula (I) have been taught by the combined teachings of the prior art (neutral lipid in an amount of 5-35 mol % and ratio of cationic lipid of formula (I) to neutral lipid of 1:1-1:2), as such, it would not have been inventive for the skilled artisan to have formulated the lipid nanoparticles of Karve to include the claimed amount of imidazolium-based cationic lipid via routine experimentation. The ratio of cationic lipids to neutral lipids is known to be results effective as Stock teaches that the ratio modulates the surface charge density of the composition (pg. 8, lines 11-13). As such, result effective variables can be optimized by routine experimentation, and it would have been prima facie obvious to optimize the amount of imidazolium-based cationic lipid in relation to the neutral lipid in the lipid nanoparticles of Karve for optimized surface charge density for efficient transfection of mRNA into a cell.
Claim 38 is rendered prima facie obvious because Karve discloses the encapsulation efficiency of the mRNA in the LNPs is greater than about 80% [0031], such as 90%, 97%, and 99% [0316]-[0341]. A prima facie case of obviousness exists because of overlap, as previously discussed.
Claim 39 is rendered prima facie obvious because Karve discloses the mRNA encodes a protein [0076] [0098].
Claim 40 is rendered prima facie obvious because Karve discloses the mRNA is used as a therapeutic agent [abstract] [0098].
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Ashlee E Wertz whose telephone number is (571)270-7663. The examiner can normally be reached Monday - Friday, 8 AM - 5 PM.
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, Sahana Kaup can be reached at 571-272-6897. 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.
/ASHLEE E WERTZ/Examiner, Art Unit 1612
Prosecution Insights