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
Applicant’s response to the restriction requirement filed on June 30. 2026 has been received and entered. Claims 9-20, 23-30, 33-35, 37, 43-46, 48, and 50-52 have been previously cancelled and claims 1-8, 21, 22, 31, 32, 36, 38-42, 47, and 49 are pending in this instant application.
Election/Restrictions
Applicant’s election of the following species SA3 as the single cationic agent dispersed primarily on the outer surface of the core, Compound 18 as the ionizable lipid of the nanoparticle core, DSPC as the4 phospholipid of the nanoparticle core, cholesterol as the structural lipid of the nanoparticle core, and DMG-PEG 2K as the PEG-lipid of the nanoparticle core in the reply filed on June 30, 2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.03(a)).
Claims 1-8, 21, 22, 31, 32, 36, 38-42, 47, and 49 read on the elected species read on the elected species and are under consideration. The election of species is deemed proper and made Final.
Priority
Acknowledgment is made of applicant's claim for priority to the filing dates of the PCT Application No. PCT/US 2023/062315 filed on Feb. 9, 2023, which claims priority to the United States Provisional Patent Application Serial No. 63/437,070, filed on January 4, 2023; United States Provisional Patent Application Serial No. 63/308,409 filed on February 9, 2022; and United States Provisional Patent Application Serial No. 63/408,409 filed on September 21, 2022.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on June 30. 2026 and November 11, 2024, are in compliance with the provisions of 37 CFR 1.97, except where noted. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Claim 21 is objected to because of the following informalities: there appears to be a typo in claim 21 as it repeats “greater than 95%”. Appropriate correction is required.
42 is objected to because each claim should be complete in themselves and avoid referencing figures in the specification. Please insert the structures with the designations in the claims. %”. Appropriate correction is required.
Claim Rejections - 35 USC § 103
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.
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.
Claim(s) 1-8, 21, 22, 31, 32, 36, 38-42, 47, and 49 are rejected under 35 U.S.C. 103 as being unpatentable over the combination of Lokugamage et al. (Nat Biomed Eng. 2021 Sep; 5(9): 1059-1068 IDS), Viger-Gravel et al. ( J. Phy. Chem. 9, 2018, 122, 2023-2081), Patel et al. (Pub. No.: US 2020/0129445; Pub. Date: Apr. 30, 2020), and Hahn et al. (Pub. No.: US 2015/0297749; Pub. Date: Oct. 22, 2015).
The claims recite a method for inducing a mucosal immune response, comprising administering to a mucosal surface of a subject a composition comprising an mRNA encoding an antigen and a nanoparticle, wherein the nanoparticle comprises a lipid nanoparticle core comprising an ionizable lipid, a phospholipid, a structural lipid, a PEG-lipid, and a cationic agent dispersed primarily on the outer surface of the core in an effective amount to induce a mucosal immune response, wherein applicant has elected the cationic agent SA3, ionizable lipid Compound 18, the phospholipid DSPC, cholesterol, and the PEG-lipid DMG-PEG 2K).
Regarding claims 1, 5-8, 31, 32, 36, 38-42, 47, and 49, Lokugamage discloses efficient delivery of therapeutic mRNA via nebulization to the lungs (respiratory mucosal cells) utilizing optimized lipid nanoparticles (LPNs) (abstract). The LPN comprising ionizable or cationic lipids, PEG-lipid, cholesterol and phospholipids (Page 2 paragraph 2); wherein the mRNA encodes and antigens, nucleases, antibodies, or other proteins (page 1 paragraph 1) that encodes for COVID-19 vaccines (page 2 paragraph 3); and wherein the phospholipid is DSPC (page 10 bottom paragraph).
But Lokugamage does not disclose the arrangement of lipid nanoparticle, the ionizable lipid as Compound 18, the PEG-lipid as DMG-PEG 2K, or the cationic lipid on the shell of the nanoparticle.
However, in the same field of endeavor comprising LPN comprising DSPC, cholesterol, PEG-lipid, and ionizable lipid encapsulating mRNA (abstract), Gravel discloses wherein the DSPC, cholesterol, PEG-lipid, and ionizable lipid encapsulating mRNA (abstract) are in the core of the LPN (page 2074 Scheme 1 LPN Structure).
Additionally in the same field of endeavor of lipid containing particles for delivery of nucleic acids comprising sterols, PEG lipids, and ionizable lipids [0004], discloses Patel discloses cationic lipids in addition to the ionizable lipid [0004], wherein the ionizable lipid is the instantly elected species Compound 18
PNG
media_image1.png
252
1270
media_image1.png
Greyscale
(page 32) and the lipid nanoparticle has the formulation of Compound 18, DSPC, Cholesterol, and PEG 2K-DMG with mRNA (page 109Table 2), the cationic compound is
PNG
media_image2.png
192
260
media_image2.png
Greyscale
or
PNG
media_image3.png
160
324
media_image3.png
Greyscale
(page 113 right column) which is the instantly claimed SA1 and SA2. However, Patel does not disclose the instantly elected species of cationic agent SA3.
Additionally, in the same field of endeavor of lipid nanoparticles for delivery of nucleic acids, Hahn discloses wherein the outer shell comprises cationic lipids ([0022]-[0023]).
Regarding claim 2, Lokugamage discloses wherein the mRNA is encapsulated within the lipid nanoparticle (page 11 bottom paragraph).
Regarding claims 2 and 22, Patel discloses wherein the mRNA is encapsulated in the nanoparticle (claim 70 and page 109 Table 2).
Regarding claim 3, Patel discloses where the nanoparticle composition may include one or more cationic and/or ionizable lipids (e.g., lipids that may have a positive or partial positive charge at physiological pH) [0336] and a zeta potential of from +5 mV to about +20 mV [0484].
Regarding claim 4, Hahn discloses the cationic lipid is 28 % w/w of the nanoparticle ([0103]/Table 2) and that the weight of the active RNA is 1/30 the weight of, the nanoparticle [0106] which is encompassed by the instantly claimed range of claim 4.
Regarding claim 21, Hanh discloses wherein the cationic agent is only on the shell and not the core [0078]
It would have been prima facie obvious to one of ordinary skill in the
art, before the effective filing date of the claimed invention to have the lipid nanoparticle arranged in a core shell configuration wherein the DSPC, cholesterol, PEG-lipid, and ionizable lipid encapsulating mRNA (abstract) are in the core of the LPN (page 2074 Scheme 1 LPN Structure) as disclosed by Gavel. One of ordinary skill in the art would be motivated to have the DSPC, cholesterol, PEG-lipid, and ionizable lipid in the core of the LPN (page 2074 Scheme 1 LPN Structure) because the drug encapsulation and delivery properties can be dependent on the structure of the LPN and the LPN are self-assembling as evidenced by Gavel (page 2073 column 2 paragraph 1-2). One or ordinary skill in the art would be motivated have a lipid nanoparticle with ionizable lipid as Compound 18, the PEG-lipid as DMG-PEG 2K, cholesterol, a cationic lipid, and phospholipid is DSPC in order to have nanoparticles with enhance cellular uptake and mRNA delivery as evidenced by Patel ([0078] and [0555]- [0556]/Tables 2-7). One of ordinary skill in the art would be motivated to include a cationic agent dispersed primarily on the outer surface of the particle so that the particle can interact by binding electrostatically with drugs, particularly nucleic acid genes forming complexes for drug delivery as evidenced by Hahn [0033]. One who would have practiced this invention would have had reasonable expectation of success because the combination of Lokugamage and Gavel had already disclosed self assembling lipid nanoparticles for delivery of mRNA to mucosal tissue, the nanoparticle comprising ionizable or cationic lipids, PEG-lipid, cholesterol and phospholipids, while Patel provided guidance with respect to the species of each components, and Hahn provided guidance to the addition of a cationic moiety to the surface of a lipid nanoparticle. Based on the combination of components disclosed by Patel it would have only required routine experimentation to arrive at the instantly claimed lipid nanoparticle.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references.
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.
Claim 1-8, 21, 22, 31, 32, 36, 38-42, 47, and 49 are rejected on the grounds of nonstatutory obviousness-type double patenting as being unpatentable over claim 1, 123-125, and 128-137 of copending application 18/709,314. Although the conflicting claims are not identical, they are not patentably distinct from each other because independent the claims application ‘314 recite the same lipid nanoparticle comprising an ionizable lipid, a phospholipid, a sterol, a PEG-lipid, a cationic agent on the surface of the particle, and a payload of polynucleotide as these instant claims, wherein the dependent claims of both application recite overlapping species of each component.
The difference between claims the instant claims and the claims of application ‘314 is that the instant claims are directed to a method for inducing a mucosal immune response, comprising administering to a mucosal surface of a subject a composition comprising an mRNA encoding an antigen and a nanoparticle. However, the specification ‘314 provides for delivery of nucleic acid molecules (mRNA0 by LPN for treatment of disorders associated with the airway epithelium [0004]. Attention is directed to MPEP 804(II)(1) In AbbVie Inc. v. Kennedy Institute of Rheumatology Trust, 764 F.3d 1366, 112 USPQ2d 1001 (Fed. Cir. 2014), the court explained that it is also proper to look at the disclosed utility in the reference disclosure to determine the overall question of obviousness in a nonstatutory double patenting context. See Sun Pharm. Indus., Ltd. v. Eli Lilly & Co., 611 F.3d 1381, 95 USPQ2d 1797 (Fed. Cir. 2010); Pfizer, Inc. v. Teva Pharm. USA, Inc., 518 F.3d 1353, 86 USPQ2d 1001 (Fed. Cir. 2008); Geneva Pharmaceuticals Inc. v. GlaxoSmithKline PLC, 349 F3d 1373, 1385-86, 68 USPQ2d 1865, 1875 (Fed. Cir. 2003). Thus the instant claims and the claims of ‘314 are obvious variants.
This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
Claim 1-8, 21, 22, 31, 32, 36, 38-42, 47, and 49 are rejected on the grounds of nonstatutory obviousness-type double patenting as being unpatentable over claim 1-9, 17, 38, 39, 42, 47-55, 58, and 62-64 of copending application 18/040,485. Although the conflicting claims are not identical, they are not patentably distinct from each other because independent the claims application ‘485 recite the same lipid nanoparticle comprising an ionizable lipid, a phospholipid, a sterol, a PEG-lipid, a cationic agent on the surface of the particle, and a payload of polynucleotide with identical features as these instant claims, wherein the dependent claims of both application recite overlapping species of each component.
The difference between claims the instant claims and the claims of application ‘485 is that the instant claims are directed to a method for inducing a mucosal immune response, comprising administering to a mucosal surface of a subject a composition comprising an mRNA encoding an antigen and a nanoparticle. However, the specification ‘485 provides for delivery of nucleic acid molecules (mRNA) by LPN for treatment of disorders associated with the airway epithelium [0004]. Attention is directed to MPEP 804(II)(1) In AbbVie Inc. v. Kennedy Institute of Rheumatology Trust, 764 F.3d 1366, 112 USPQ2d 1001 (Fed. Cir. 2014), the court explained that it is also proper to look at the disclosed utility in the reference disclosure to determine the overall question of obviousness in a nonstatutory double patenting context. See Sun Pharm. Indus., Ltd. v. Eli Lilly & Co., 611 F.3d 1381, 95 USPQ2d 1797 (Fed. Cir. 2010); Pfizer, Inc. v. Teva Pharm. USA, Inc., 518 F.3d 1353, 86 USPQ2d 1001 (Fed. Cir. 2008); Geneva Pharmaceuticals Inc. v. GlaxoSmithKline PLC, 349 F3d 1373, 1385-86, 68 USPQ2d 1865, 1875 (Fed. Cir. 2003). Thus the instant claims and the claims of ‘485 are obvious variants.
This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ANNA R FALKOWITZ whose telephone number is (571)270-3386. The examiner can normally be reached Monday - Friday 9am - 5pm.
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, Zachariah Lucas can be reached at (571) 272-0905. 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.
/ANNA R FALKOWITZ/
Primary Examiner, Art Unit 1600
Prosecution Insights