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 .
Status of Application/Amendment/Claims
This Office action is in response to the communications filed on August 4, 2025.
Currently, claims 120, 123, 131-140, 145, and 150 are pending in the instant application. Claims 135 and 139 are withdrawn from further consideration as being drawn to a nonelected invention/species, there being no allowable generic or linking claim. Accordingly, claims 120, 123, 131-134, 136-138, 140, 145, and 150 are under examination on the merits in the instant application.
The following rejections are either newly applied or are reiterated and are the only rejections and/or objections presently applied to the instant application.
Response to Arguments and Amendments
Terminal Disclaimer
The terminal disclaimer filed on August 4, 2025 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of Application Nos. 18,283,344; 18,311,274; 18/778,439; 18/778,717 has been reviewed and is accepted. The terminal disclaimer has been recorded.
Withdrawn Rejections
Any rejections/objections not repeated in this Office action are hereby withdrawn.
Maintained Rejections
Claim Rejections - 35 USC § 112
Claims 120, 123, 131-134, 136-138, 140, and 145 remain rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement for the reasons as set forth in the Office action mailed on March 14, 2025 and for the reasons set forth below.
Applicant's arguments filed on August 4, 2025 have been fully considered but they are not persuasive. Applicant argues that the claims as amended to recite “aerosol particles” and “consists essentially of” are sufficient to overcome the rejection. Contrary to applicant’s argument, the aforementioned newly added limitations are not sufficient to comply with the written description requirement, because the species and generic description disclosed in the instant specification are not sufficient to support the entire genus of the rejected claims, which encompass the recited components at any molar %. See claims 120, 136-138, and 140 reciting no molar %; claims 123 and 131-134 reciting a range of molar % for a single component; and claim 145 reciting a range of molar % for each of the five components. As explained in the last Office action, the instant specification at best adequately describes a single molar ratio for the five components, wherein the single species is not representative of the “sufficient variety” pertaining to the required molar % of each of the five components for the LNP composition in the claimed aerosol particles. For instance, for claim 145 reciting “about 20% to about 40%” molar % for DODAP, the disclosed LNP comprising the 20 molar % DODAP combined with 19.05% for 4A3-SC7 and DOPE, 38.9% cholesterol, and 3.81% of DMG-PEG cannot reflect an aerosol particles comprising LNP with 40 molar % DODAP combined with concurrently and necessarily altered molar % for 4A3-SC7, DOPE, cholesterol, and DMG-PEG.
Accordingly, this rejection is maintained.
Claim Rejections - 35 USC § 103
Claims 120, 123, 131-134, 136-138, 140, 145, and 150 remain rejected under 35 U.S.C. 103 as being unpatentable over Cheng et al. in view of Woo et al. and Zhou et al. for the reasons as set forth in the Office action mailed on March 14, 2025 and for the reasons set forth below.
Applicant's arguments filed on August 4, 2025 have been fully considered but they are not persuasive. Applicant argues that the claims are not obvious because the instantly recited “aerosol composition comprising aerosol particles” differentiate the claimed structure from the cited art. In so arguing, applicant asserts that there is there is “insufficient” motivation to change intravenous formulation of Cheng to an aerosol composition because “a person of skill in the art would know that one could not merely leap from one administration route to another in producing effective compositions for therapeutic applications.” Applicant further alleges that the examiner failed to articulate a reason for changing from intravenous delivery to nebulized delivery. Contrary to applicant’s arguments, one of ordinary skill in the relevant art would have reasonably expected that a composition formulated for direct, local lung delivery (e.g., aerosol formulation) would be more therapeutically effective for the treatment of a lung-associated disease/condition. Note that applicant’s elected invention pertaining to an mRNA encoding DNAI1 was known to be useful “for use in the treatment of primary ciliary dyskinesia (PCD)”, wherein it was already known in the prior art to make and use an LNP-containing “aerosol” composition for “nebulized delivery of DNAI1” for the treatment of PCD as evidenced by Woo. As such, one of ordinary skill in the art would have had more than sufficient motivation to replace the intravenously formulated composition of Cheng with the aerosol composition comprising LNP encapsulating an mRNA encoding DNAI1 so as to provide “nebulized delivery of DNAI1” to “bronchioles, trachea and bronchi” of the lungs of a subject having PCD. Note that this rationale is already provided in the last Office action.
Applicant argues that the teachings of Woo “are not connected to the teachings of particular formulation in Cheng.” In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In the instant case, there is no teaching in Woo that the aerosol formulation comprising an LNP encapsulating the DNAI1 mRNA can be made only when the LNP must comprise the disclosed components. That is, there is no teaching in Woo that an aerosol formulation can only be made exclusively for the LNP disclosed in Woo but cannot be made with other types of LNP. For instance, applicant did not point out any particular passage in Woo that teaches that the aerosol formulation comprising Cheng’s LNP would fail to be delivered to the lungs or would not be useful for delivering the DNAI1 mRNA for PCD treatment purpose. In fact, Woo also teaches the following consistent with Cheng’s intravenous formulation in paragraph 0292: “Most commonly, the therapeutically effective dose comprising the mRNA encoding dynein axonemal intermediate chain protein 1 is administered to the subject by intravenous administration.” Further, consistent with Cheng’s teachings that the LNP formulation can be administered in other routes (“intranasally”, “intratracheally”, or “via inhalation”; see paragraph 0066; emphasis added), Woo also teaches the following in paragraph 0293: “Alternatively or additionally, liposomally encapsulated mRNAs and compositions of the invention may be administered in a local rather than systemic manner, for example, via injection of the pharmaceutical composition directly into a targeted tissue, preferably in a sustained release formulation. Local delivery can be affected in various ways, depending on the tissue to be targeted. For example, aerosols containing compositions of the present invention can be inhaled (for nasal, tracheal, or bronchial delivery)”. (emphasis added). Hence, one of ordinary skill in the relevant art would have reasonably deemed that the “intranasally”, “intratracheally”, and “via inhalation” routes taught by Cheng’s LNP formulation delivery do indeed encompass use of “aerosols” containing Cheng’s LNP formulation in view of Woo, and furthermore, as explained in the last Office action and reiterated hereinabove, one skilled in the relevant art would have been motivated to formulate Cheng’s LNP formulation containing the DNAI1 mRNA as an aerosol formulation for direct, local delivery of the therapeutic mRNA to the lungs for the purpose of treating PCD. As such, one of ordinary skill in the relevant art would not dismiss Woo’s teachings as being irrelevant or “not connected” to the teachings of Cheng or as being inapplicable to Cheng’s LNP.
Applicant argues that the “reduced cost” is not supported by facts. In response, it is noted that it is factually apparent that “5A2” exemplified in Cheng’s 20% DODAP-containing LNP is a longer chain than “4A3”, and similarly, “SC8” exemplified in Cheng’s 20% DODAP-containing LNP is a longer chain than “SC7” as evidenced by the express disclosures of the structures of each of 5A2, 4A3, SC7, and SC8 in Zhou. As such, it follows that more material is required to synthesize Cheng’s exemplified “5A2-SC8” than the synthesis of the shorter “4A3-SC7”, thereby supporting the examiner’s statement that “one of ordinary skill in the art would have reasonably expected that synthesis of 4A3-SC7 would be more cost-effective compared to that of Cheng’s 5A2-SC8”, wherein such statement is supported by “facts” disclosed in Zhou relating to the structural differences of 5A2, 4A3, SC7, and SC8, whose structures are clearly shown at page 9 of the last Office action.
Applicant argues that the cited references fail to provide a reasonable expectation of success because one skilled in the art would have understood that “aerosolizing LNP compositions is not a trivial task, and thus unpredictable.” In so arguing, applicant points out a post-filing reference published in the year of 2023. Since applicant did not provide a legible copy of the reference for examiner’s consideration, the examiner cannot consider and verify the teachings of the 2023 reference. Further, the passage quoted by applicant does not appear to teach that it was known to be unpredictable to make an aerosol formulation comprising an LNP encapsulating an mRNA. Note that the instantly rejected claims are merely directed to a composition, not a therapeutic method. Hence, the passage’s teaching pertaining to “therapeutic goal” is far from teaching that making an aerosol formulation comprising aerosol LNP particles was known to be technically unpredictable, thereby lacking a reasonable expectation of success in making the claimed composition before the effective filing date sought in the instant application.
Accordingly, this rejection is maintained.
Double Patenting
Claims 120, 123, 131-134, 136-138, 140, 145, and 150 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-65 of U.S. Patent No. 11,642,421 in view of Cheng et al., Woo et al., and Zhou et al. for the reasons as set forth in the Office action mailed on March 14, 2025 and for the reasons set forth below.
Applicant's arguments filed on August 4, 2025 have been fully considered but they are not persuasive. Applicant argues that the ‘421 patent claims do not recite “aerosol particles” thus the rejection should be withdrawn. In response, it is noted that the instant rejection is not an anticipation-type rejection but an obviousness-type rejection, wherein it was deemed obvious to make an aerosol formulation comprising the lipid nanoparticles (LNP) encapsulating an DNAI1 mRNA of the ‘421 patent claims in view of the teachings of Cheng, Woo, and Zhou as explained in the last Office action. Accordingly, this rejection is maintained.
Claims 120, 123, 131-134, 136-138, 140, 145, and 150 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,786,610 in view of Cheng et al., Woo et al., and Zhou et al. for the reasons as set forth in the Office action mailed on March 14, 2025 and for the reasons set forth below.
Applicant's arguments filed on August 4, 2025 have been fully considered but they are not persuasive. Applicant argues that the ‘610 patent claims do not recite “aerosol particles” thus the rejection should be withdrawn. In response, it is noted that the instant rejection is not an anticipation-type rejection but an obviousness-type rejection, wherein it was deemed obvious to make an aerosol formulation comprising the lipid nanoparticles (LNP) encapsulating an mRNA of the ‘610 patent claims reciting “for administration to lung cells of a subject” in view of the teachings of Cheng, Woo, and Zhou as explained in the last Office action. Accordingly, this rejection is maintained.
Claims 120, 123, 131-134, 136-138, 140, 145, and 150 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 125-131 of Application No. 18/282,181 in view of Cheng et al., Woo et al., and Zhou et al. for the reasons as set forth in the Office action mailed on March 14, 2025 and for the reasons set forth below.
Applicant's arguments filed on August 4, 2025 have been fully considered but they are not persuasive. Applicant argues that the ‘181 claims do not recite “aerosol particles” thus the rejection should be withdrawn. In response, it is noted that the instant rejection is not an anticipation-type rejection but an obviousness-type rejection, wherein it was deemed obvious to make an aerosol formulation comprising the lipid nanoparticles (LNP) encapsulating an mRNA of the ‘181 claims reciting “formulated for administration to lung cells of a subject” in view of the teachings of Cheng, Woo, and Zhou as explained in the last Office action. Accordingly, this rejection is maintained.
Claims 120-121, 123, 131-134, 136-138, and 145-150 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 17-18, 21-22, 24, 27, 29, 42-43, 47, and 51-53 of Application No. 18/283,523 for the reasons as set forth in the Office action mailed on March 14, 2025 and for the reasons set forth below.
Applicant's arguments filed on August 4, 2025 have been fully considered but they are not persuasive. Applicant argues that the ‘523 claims do not recite “aerosol particles” thus the rejection should be withdrawn. In response, applicant’s attention is directed to the fact that the ‘523 claims do encompass and recite “an aerosol composition.” See claims 47 and 51. As such, the “aerosol composition” comprising lipid nanoparticles (LNP) encapsulating an mRNA as claimed in the ‘523 claims do in fact inherently recite “aerosol particles”, contrary to applicant’s argument. Accordingly, this rejection is maintained.
Claims 120, 123, 131-134, 136-138, 140, 145, and 150 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-28 of U.S. Patent No. 12,257,318 B2 (issued in Application No. 18/431,504) for the reasons as set forth in the Office action mailed on March 14, 2025 and for the reasons set forth below.
Applicant's arguments filed on August 4, 2025 have been fully considered but they are not persuasive. Applicant argues that the ‘318 patent claims do not recite “aerosol particles” thus the rejection should be withdrawn. In response, applicant’s attention is directed to the fact that the ‘318 patent claims do encompass and recite “an aerosol composition.” See claim 11. See also claims 12-14 reciting “droplet size of the aerosol droplets”. As such, the “aerosol composition” comprising “aerosol droplets” comprising lipid nanoparticles (LNP) encapsulating an mRNA as claimed in the ‘318 patent claims do in fact inherently recite “aerosol particles”, contrary to applicant’s argument. Accordingly, this rejection is maintained.
Claims 120-121, 123, 131-134, 136-138, and 145-150 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 8, 10-12, 15-24, and 31-33 of Application No. 18/461,021 in view of Davis et al., Cheng et al., Woo et al., and Zhou et al. for the reasons as set forth in the Office action mailed on March 14, 2025 and for the reasons set forth below.
Applicant's arguments filed on August 4, 2025 have been fully considered but they are not persuasive. Applicant argues that the ‘021 claims do not recite “aerosol particles” thus the rejection should be withdrawn. In response, it is noted that the instant rejection is not an anticipation-type rejection but an obviousness-type rejection, wherein it was deemed obvious to make an aerosol formulation comprising the lipid nanoparticles (LNP) encapsulating an mRNA of the ‘021 claims in view of the teachings of Davis, Cheng, Woo, and Zhou as explained in the last Office action. Accordingly, this rejection is maintained.
Claims 120-121, 123, 131-134, 136-138, and 145-150 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5-6, 8-30, and 32-36 of Application No. 18/593,245 for the reasons as set forth in the Office action mailed on March 14, 2025 and for the reasons set forth below.
Applicant's arguments filed on August 4, 2025 have been fully considered but they are not persuasive. Applicant argues that the ‘245 application is a later-filed application thus the rejection should be withdrawn. In response, it is noted that the instant rejection is not the only outstanding rejection in the instant application. Hence, this rejection is maintained.
Claims 120-121, 123, 131-134, 136-138, 140, and 145-150 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of Application No. 18/596,141 for the reasons as set forth in the Office action mailed on March 14, 2025 and for the reasons set forth below.
Applicant's arguments filed on August 4, 2025 have been fully considered but they are not persuasive. Applicant argues that the ‘141 application is a later-filed application thus the rejection should be withdrawn. In response, it is noted that the instant rejection is not the only outstanding rejection in the instant application. Hence, this rejection is maintained.
Claims 120-121, 123, 131-134, 136-138, and 145-150 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 17-92 of Application No. 19/006,037 for the reasons as set forth in the Office action mailed on March 14, 2025 because applicant did not provide any substantial rebuttal arguments addressing the supposed errors of this rejection. Hence, this rejection is maintained for the reasons of record.
New Rejections Necessitated by Amendment
Claim Rejections - Improper Markush Grouping
Claim 120 is rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984).
Note that “the phrase "Markush claim” means any claim that recites a list of alternatively useable species regardless of format.” See MPEP §2173.05(h).
Note that the instant rejection is judicially approved as set forth in “Supplementary Examination Guidelines for Determining Compliance with 35 U.S.C. 112 and for Treatment of Related Issues in Patent Applications” in Federal Register, Volume 76, Number 27, published on February 9, 2011, which expressly states the following:
“A Markush claim contains an “improper Markush grouping” if: (1) The species of the Markush group do not share a “single structural similarity,” or (2) the species do not share a common use…When an examiner determines that the species of a Markush group do not share a single structural similarity or do not share a common use, then a rejection on the basis that the claim contains an “improper Markush grouping” is appropriate.” (emphasis added). See page 7166, middle column.
The list of alternatively recited species of DODAP, 14:0 EPC, and 14:0 TAP in lines 7-9 of claim 120 is improper because the alternatives defined by the Markush grouping, see the definition of “Markush claim” as set forth above, do not share a single structural similarity.
In addition, even more interestingly, the instant specification appears to categorize 14:0 EPC and 14:0 TAP as being a distinct lipid from DODAP such that DODAP is categorized as “ionizable cationic lipid”, whereas “14:0 EPC” and “14:0 TAP” are categorized as “permanently cationic lipid”. See paragraphs 0039-0041. Hence, the newly introduced limitation reciting three different species is found to contain an improper grouping of alternatively recited species.
Double Patenting
The text of the judicially created doctrine not included in this action can be found in a prior Office action.
Claims 120, 123, 132-134, 136-138, and 140 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 12,121,610 B2.
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are anticipated by the ‘610 patent claims drawn to an aerosol composition comprising the structure corresponding to 4A3-SC7 and “1,2-dioleoyl-sn-glycero-3-ethylphosphocholine” at about 20% as well as an mRNA encoding dynein exonemal intermediate chain 1.
Claims 120, 123, 132-134, 136-138, and 140 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 12,257,318 B2.
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims even including “14:0 EPC” and “14:0 TAP” are anticipated by the ‘318 patent claims drawn to an “aerosol” pharmaceutical composition comprising “14:0 TAP” (see claim 29) and “14:0 EPC” (see claim 30).
Claims 120, 123, 132-134, 136-138, and 140 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-28 of U.S. Patent No. 12,337,068 B2.
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are anticipated by the ‘068 patent claims that require an aerosolized pharmaceutical composition comprising the structure corresponding to 4A3-SC7 and “14:0 EPC” as well as an mRNA encoding dynein exonemal intermediate chain 1 (DNAI1).
Claims 120, 123, 132-134, 136-138, and 140 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 and 25 of copending Application No. 18/778,746.
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are anticipated by and/or overlap in scope with the ‘746 claims drawn to and require an aerosol composition comprising the structure corresponding to 4A3-SC7 and “ethylphosphocholine” as well as an mRNA, wherein “ethylphosphocholine” is described to read on “1,2-dioleoyl-sn-glycero-3-ethylphosphocholine” (14:0 EPC) and the mRNA is described read on “DNAI1 mRNA” in the ‘746 specification.
Claims 120, 123, 132-134, 136-138, and 140 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of copending Application No. 18/780,382.
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are anticipated by and/or overlap in scope with the ‘746 claims drawn to an aerosol composition comprising the structure corresponding to 4A3-SC7 and “1,2-dimyristoyl-3-trimethylammonium-propane” as well as a polynucleotide including an mRNA encoding dynein exonemal intermediate chain 1.
Claims 120, 123, 132-134, 136-138, and 140 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7, 10-16, and 18-21 of copending Application No. 18/797,360.
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are anticipated by and/or overlap in scope with the ‘360 claims drawn to and require an aerosol composition comprising the structure corresponding to 4A3-SC7 and “14:0 TAP” as well as a polynucleotide including an mRNA and sgRNA, wherein the mRNA is described to read on an mRNA encoding dynein exonemal intermediate chain 1 in the ‘360 specification.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DANA H SHIN whose telephone number is (571)272-8008. The examiner can normally be reached Monday-Thursday: 8am - 6:30pm.
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/DANA H SHIN/Primary Examiner, Art Unit 1635