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 .
Receipt is acknowledged of Amendments, Remarks and an IDS filed on 07/10/2025 and an IDS filed on 05/12/2025. Claims 120, 128, 138, 141, 143 and 145 have been amended, claims 122-125 and 136 have been canceled and no new claims have been added. Accordingly, claims 120-121, 126-128 and 130-149 remain pending and claims 127-128, 133-135, 140 and 143-149 remain withdrawn. Claims 120-121, 126, 130-132, 137-139 and 141-142 are under examination on the merits.
Rejections and/or objections not reiterated from the previous Office Action are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set of rejections and/or objections presently being applied to the instant application.
Claim Objections
Claim 138 is objected to under 37 CFR 1.75 as being a substantial duplicate of claim 137. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m). Both claims 137 and 138 depend on claim 120 and are directed to the ionizable cationic lipid, 4A3-SC7, being present at a molar percentage of from about 15 to about 30%.
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.
Claims 120-121, 126, 130-132, 137-139 and 141-142 are rejected under 35 U.S.C. 103 as being unpatentable over Heartlein et al (US 20150157565) in view of Lockhart et al (WO 2017205767), Cheng et al (WO 2020051223) and Karve et al (WO 2020106946).
Heartlein et al teach compositions comprising mRNA formulated for pulmonary administration and related methods for delivery of the mRNA and/or encoded protein to a non-lung cell or tissue. The compositions and methods may be used to prevent or ameliorate the symptoms of diseases associated with the mRNA encoded protein (See abstract).
The disclosure provides a composition for pulmonary delivery of messenger RNA (mRNA) comprising mRNA encoding a protein and a lipid carrier vehicle, wherein the composition is formulated such that once administered to the lung, it results in delivery of the mRNA and the protein to a non-lung cell or tissue (See [0016] and [0066]).
It is stated that the said composition is administered to the lung by aerosolization, such as by intratracheal aerosolization, or by nebulization. The said composition is administered to the lung of a subject using a device such as a metered dose inhaler, jet-nebulizer, ultrasonic nebulizer, etc, (See [0017] and [0129]).
Further disclosed is that, the mRNA encoding a protein is involved in cellular metabolism, DNA repair, transcription and/or translation. The mRNA may encode a protein that is associated with a disease or disorder, such as a condition with mitochondrial DNA deletions (See [0019], [0021], [0069] and [0084]).
The said lipid carrier vehicle may be a liposome, comprising one or more cationic lipids, one or more non-cationic lipids, one or more cholesterol-based lipids and one or more PEG-modified lipids. The said one or more cationic lipid may be an ionizable lipid, or the one or more cationic lipid may be a cholesterol-derived cationic lipid. The said one or more cationic lipids may be selected from C12-200, HGT4003, HGT5000, HGT5001, RE-1, RE-2, RE-3, ICE, GL-67, DLinKC2-DMA, DODAP, DODMA, DLinDMA, CLinDMA, DOTMA and combinations thereof (See [0027], [0108 and [0110]).
It is further disclosed that a suitable lipid carrier vehicle maybe formulated as a lipid nanoparticle. The contemplated lipid nanoparticles may be prepared by including multi-component lipid mixtures of varying ratios employing one or more cationic lipids, non-cationic lipids, cholesterol-based lipids, and PEG-modified lipids. Examples of suitable lipids include phosphatidyl compounds (e.g., phosphatidylglycerol, phosphatidylethanolamine, etc,) (See [0101]).
Exemplary non-cationic or neutral lipids can be chosen from DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine), DOPE (1,2-dioleyl-sn-glycero-3-phosphoethanolamine), DMPE (1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine) (i.e, 14:0 EPC), cholesterol, etc. The said non-cationic lipid may comprise a molar ratio of 5% to about 90%, or preferably about 10% to about 70% of the total lipid present in the transfer vehicle (See [0111] and [0118]).
The said cationic lipid may comprise a molar ratio of about 1% to about 90%, about 10% to about 40% of the total lipid present in the transfer vehicle (See [0115]).
Heartlein et al also teach that a suitable transfer vehicle may be prepared using C12-200, DOPE, chol, DMG-PEG2K at a molar ratio of 40:30:25:5, or DODAP, DOPE, cholesterol, DMG-PEG2K at a molar ratio of 18:56:20:6, etc. The selection of cationic lipids, non-cationic lipids and/or PEG-modified lipids which comprise the lipid nanoparticle, as well as the relative molar ratio of such lipids to each other, is based upon the characteristics of the selected lipid(s), the nature of the intended target cells, the characteristics of the mRNA to be delivered (See [0119] and [0120]).
It is disclosed that the said formulations are “formulated such that they may be aerosolized or otherwise delivered as a particulate liquid or solid prior to or upon administration to the subject. Such compositions may be administered with the assistance of one or more suitable devices for administering such solid or liquid particulate compositions (such as, e.g., an aerosolized aqueous solution or suspension) to generate particles that are easily respirable or inhalable by the subject. In some embodiments, such devices (e.g., a metered dose inhaler, jet-nebulizer, ultrasonic nebulizer, dry-powder-inhalers, propellant-based inhaler or an insufflator) facilitate the administration of a predetermined mass, volume or dose of the compositions (e.g., about 0.5 mg/kg of mRNA per dose) to the subject. For example, in certain embodiments, the compositions of the invention are administered to a subject using a metered dose inhaler containing a suspension or solution comprising the composition and a suitable propellant….. In certain embodiments, compositions of the invention formulated as respirable particles are appropriately sized such that they may be respirable by the subject or delivered using a suitable device (e.g., a mean D50 or D90 particle size less than about ……10 μm, 5 μm, 2.5 μm or smaller)” (See [0129]).
Heartlein et al teach mRNA encoding a protein such as those for treating a DNA depleted condition. However, there is no express disclosure on the protein being DNAI1. This is known in the art as taught by Lockhart et al. Heartlein et al does not expressly disclose wherein the cationic lipid is 4A3-SC7. This would have been obvious over Cheng et al. Heartlein et al also is silent with regard to the concentration of polynucleotide. This is known in the art as taught by Karve et al.
Lockhart et al teach polynucleotides encoding peptides, proteins, enzymes, and functional fragments thereof which can be effectively delivered to an organ, such as the lung, and expressed within cells of the organ. The polyribonucleotides of the disclosure can be used to treat a disease or condition associated with cilia maintenance and function, impaired function of the axoneme, such as DNAI1 or DNAH5 (See abstract).
Lockhart et al show, by way of Figures, an agarose gel illustrating the production of capped and uncapped DNAI1 RNA (Fig. 1), the translations of DNAI1 mRNA in HEK-293 cells (Fig. 2), and post transcriptionally poly-adenylated RNA transcript encoding dynein axonemal intermediate chain 1 (DNAI1) (See [0011]-[0016]).
It is disclosed that the said composition comprises a nucleic acid construct encoding dynein axonemal intermediate chain 1 (DNAI1), and upon translation within the cells of a subject the construct yields a polypeptide that treats a subject having or at risk of having primary ciliary dyskinesia. The DNAI1 gene can provide instructions for making a protein that is part of a group (complex) of proteins called dynein (See [0059]).
Lockhart et al disclose a composition comprising an engineered polyribonucleotide which can be encapsulated or formulated with a pharmaceutical carrier. The formulation may be poly(lactic-co-glycolic acid) (PLGA) microspheres, lipidoids, liposome, cationic lipids, etc, and combinations thereof. The said composition can comprise from about 1% to about 99% weight by volume of a carrier system (See [0006] and [00149]). A lipidoid or lipid nanoparticle which may be used as a delivery agent may include a lipid which may be selected from the group consisting of C12-200, MD1, 98N12-5, DLin-DMA, DLin-K-DMA, DLin-KC2-DMA, DLin-MC3 -DMA, PLGA, PEG, PEG-DMG, PEGylated lipids and analogues thereof. A suitable nanoparticle can comprise one or more lipids in various ratios. For example, a composition can comprise a 40:30:25:5 ratio of C12-200:DOPE:Cholesterol:DMG-PEG2000. A nanoparticle can include at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 lipids or another suitable number of lipids. The PEG lipid may be selected from, PEG-c-DOMG, PEG-DMG. The fusogenic lipid may be DSPC (See [00154]-[00155]). A nanoparticle can be a particle of particle size from about 10 nanometers (nm) to 5000 nm, or from 10 nm to 1000 nm (See [00153]).
Lockhart et al disclose that for administration by inhalation, the active compounds can be in a form as an aerosol, a mist, a vapor, a spray, or a powder, which may be conveniently delivered in the form of an aerosol spray presentation from pressurized packs or a nebulizer. The said compositions comprising the engineered polyribonucleotides include formulating the compounds with one or more inert, pharmaceutically-acceptable excipients or carriers to form a solid, semi-solid, or liquid composition. Liquid compositions include, solutions or suspensions (See [00216] and [00221]).
Cheng et al teach compositions which shown preferential targeting or delivery of a nucleic acid composition to a particular organ, in some embodiments, the composition comprises a steroid or sterol, an ionizable cationic lipid, a phospholipid, a PEG lipid, and a permanently cationic lipid which may be used to deliver a nucleic acid (See abstract).
Cheng et al teach compositions comprising cholesterol, DMG-PEG, DOPE and further comprising 3A5-SC8, 3A3-SC8, 4A1-SC8, 4A3- SC8, 5A2-SC8 with five tails, or 5A2-SC8 with six tails, or 5A2-SC8 or DOTAP (See [0033]).
In one embodiment, the molar ratio of 5A2- SC8/DOPE/Chol/DMG-PEG were fixed as 15/15/30/3 (See [0067]).
Cheng et al teach compositions containing one or more lipids mixed with the cationic ionizable lipids to create a composition, wherein, the cationic ionizable lipids are mixed with 1, 2, 3, 4, or 5 different types of lipids. The said cationic ionizable lipids compositions comprise at least a steroid or a steroid derivative, a PEG lipid, and a phospholipid. [00143]
Cheng et al further disclose a composition comprising one or more selective organ targeting (SORT) compound which leads to the selective delivery' of the composition to a particular organ. This compound may be a lipid, a small molecule therapeutic agent, a sugar, a vitamin, or a protein. The said selective organ targeting (SORT) compound is present in the composition in a molar ratio from about 20% to about 35% (See [00133]).
Cheng et al disclose that the said pharmaceutical compositions preferentially deliver the nucleic acid to a target organ selected from the lungs. The said compositions are formulated for administration orally, intravenously, via inhalation, etc, and comprise an acceptable carrier including a solvent or solution (See [0038]).
Karve et al teach an improved method of treating cystic fibrosis (CF) in a human subject, the method comprising administering a composition comprising an mRNA encoding a cystic fibrosis transmembrane conductance regulator (CFTR) protein at a concentration of 0.5 mg/mL or greater to a human subject via nebulization, at a suitable nebulization rate, e.g, at least 0.2 mL/minute (See abstract). The concentration of the mRNA encoding the CFTR protein ranges from 0.5 mg/mL to 0.8 mg/mL, optionally wherein the concentration is 0.6 mg/mL (See [0007], [0221] and claims 1-2).
Disclosed is a particularly effective method of administering liposome-encapsulated CFTR mRNA by nebulization to the lungs of a human subject for the treatment of cystic fibrosis (See [0006]). The said liposome comprises one or more cationic lipids, one or more non-cationic lipids, and one or more PEG-modified lipids. The non-cationic lipid may be a phospholipid such as DOPE (See [0015]).
A suitable nebulizer produces droplets with an average size between 4 µm and 6 µm (See [0012]). Inhaled aerosol droplets of a particle size of 1-5 µm can penetrate into the narrow branches of the lower airways. Aerosol droplets with a larger diameter are typically absorbed by the epithelia cells lining the oral cavity, and are unlikely to reach the lower airway epithelium and the deep alveolar lung tissue (See [0208]).
In a preferred embodiment, Karve et al disclose a concentration of the CO-hCFTR mRNA being 0.6 mg/ml, wherein a nebulizer was used to administer the CO-hCFTR composition by nebulization at a nebulization rate of approximately 0.3 mL/minute (See [0338]).
Karve et al teach that the nominal nitrogen/phosphorus (N/P) charge ratio which refers to the positively charged nitrogens in the cationic lipid and the negatively charged phosphodiester linkages within mRNA is about between 1 and 10 (See [0148]).
It would have been prima facie obvious to a person of ordinary skilled in the art at the time the invention was made to have combined the teachings of Cheng et al, Karve et al and Lockhart et al with that of Heartlein et al to arrive at the instant invention.
It would have been obvious to do so because Heartlein et al teach compositions for delivery of a polynucleotide to the pulmonary system comprising a polynucleotide and a lipid carrier comprising one or more ionizable cationic lipid, one or more phospholipid, one or more cholesterol, and a polyethylene glycol-conjugated lipid wherein the formulation has a respirable particle size of less than 10 micron.
Heartlein et al teach a composition for pulmonary delivery of messenger RNA (mRNA) comprising mRNA encoding a protein and a lipid carrier vehicle, wherein vehicle may be prepared using C12-200, DOPE, chol, DMG-PEG2K at a molar ratio of 40:30:25:5, or DODAP, DOPE, cholesterol, DMG-PEG2K at a molar ratio of 18:56:20:6.
Heartlein et al teach the pulmonary delivery of mRNA encoding a protein, but do not expressly disclose an embodiment wherein the said protein is DNAI1. However, one of ordinary skill in the art would have been motivated to select DNAI1 as the said protein based on the prior art’s teachings including Lockhart et al, because Lockhart et al teach the advantages of delivering mRNA encoding DNAI1, including effective treatment of primary ciliary dyskinesia.
Heartlein et al teach the lipid carrier mixture comprising one or more of cationic lipids and provide examples of such lipids, but do not expressly disclose an embodiment wherein the said lipid is 4A3-SC7. However, one of ordinary skill in the art would have been motivated to select 4A3-SC7 or 4A3-SC8 as the said cationic lipid based on the prior art’s teachings including Cheng et al, because Cheng et al teach similar compositions wherein the cationic lipid may be 4A3- SC8, 5A2-SC8 or DOTAP.
Cheng et al teach a composition comprising 4A3- SC8, 5A2-SC8 or DOTAP. While there is no express recitation of the lipid compound 4A3-SC7, it would have been obvious to one of ordinary skill in the art to select either compound because the two compounds are homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups), which is exactly the difference between SC7 and SC8. One of ordinary skill in the art would have expect that the SC7 would function as an ionizable lipid the same as SC8 because they are so structurally similar.
In other words, the claims are rejected on the well-established principle that compounds of sufficient structure similarity are prima facie obvious even in the absence of a teaching to modify. MPEP 2144.09. Compounds 4A3-SC7 and 4A3-SC8 are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties.
Additionally, Heartlein et al teach that the said compositions can be a solution and delivered to a subject via nebulizer, but are silent with regard to the concentration of the polynucleotide in the solution (i.e the droplets). One of ordinary skill in the art wishing to follow Heartlein et al’s teachings to prepare the said formulations would have been motivated to have looked in the art for guidance on the concentrations. Karve et al teach a similar composition ion solution form for nebulization and provides guidance on the said concentrations in mg/mL. As such it would have been obvious to combine the teachings of Karve et al with that of Heartlein et al to arrive at the claimed invention.
The claims would have been obvious because a person of ordinary skill has good reasons to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.
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 120-121 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 6-7 of U.S. Patent No. 11,786, 610 in view of Heartlein et al (US 20150157565) Cheng et al (WO 2020051223) and Karve et al (WO 2020106946). The Obviousness Double Patenting rejection is appropriate because while the conflicting claims are not identical, the examined claims are not patentably distinct from the reference claims. The examined claims would have been obvious over the reference claims in view of Heartlein et al, Cheng et al and Karve et al.
Specifically, the examined claims are drawn to an aerosol composition for delivering a polynucleotide to lung cells, comprising aerosol droplets, wherein the aerosol droplets comprise the polynucleotide assembled with a lipid composition, which lipid composition comprises: (i) an ionizable cationic lipid being 4A3-SC7, (ii) a phospholipid; (iii) a cholesterol; and (iv) a polyethylene glycol-conjugated lipid (PEG-lipid), wherein the aerosol droplets have a mass median aerodynamic diameter (MMAD) from about 0.5 micron (μm) to about 10 μm and wherein the concentration of the polynucleotide in the droplets is between about 0.5 and 2 mg/mL.
The reference claims are drawn to a composition comprising a nucleic acid construct encoding a polypeptide at least 95% identical to a coiled-coil domain containing 39 (CCDC39) polypeptide, wherein said composition is formulated for administration to lung cells of a subject, wherein said composition comprises a cationic lipid; a fusogenic lipid; a cholesterol; and a polyethylene glycol (PEG) lipid; and wherein said nucleic acid construct comprises 1-methylpseudouridine.
The differences are that reference claims do not recite wherein the cationic lipid is 4A3-SC7, the droplet size or the concentration of the polynucleotide in the droplets. However, these modifications would have been obvious in view of the reference claims and the teachings of Heartlein et al, Cheng et al and Karve et al.
Heartlein et al teach compositions comprising mRNA formulated for pulmonary administration comprising mRNA encoding a protein and a lipid carrier vehicle. The lipid vehicle of Heartlein et al comprises an ionizable cationic lipid, cholesterol, phospholipid and a PEG-lipid as well as other lipids. Heartlein et al discloses that the said formulations are formulated as respirable particles with a mean D50 or D90 particle size less than about 10 μm, 5 μm, 2.5 μm or smaller. Cheng et al teach that the lipid composition may comprise one or more lipids including 4A3-SC7. Karve et al teach a similar composition ion solution form for nebulization and provides guidance on the said concentrations in mg/mL.
It would have been obvious to one of ordinary skill in the art to have looked in the art for other suitable lipids that can be added to the compositions of reference claims including a cholesterol as taught by Heartlein et al and 4A3-SC7 as taught by Cheng et al with a reasonable expectation of success.
Claims 120-121, 126, 130-132, 137-139 and 141-142 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-32 of U.S. Patent 12,121,610 in view of Lockhart et al (WO 2017205767) and Karve et al (WO 2020106946). Although the claims at issue are not identical, they are not patentably distinct from each other because the examined claims would have been obvious over the reference claims in view of Lockhart et al and Karve et al.
Specifically, the examined claims are drawn to an aerosol composition for delivering a polynucleotide to lung cells, comprising aerosol droplets, wherein the aerosol droplets comprise the polynucleotide assembled with a lipid composition, which lipid composition comprises: (i) an ionizable cationic lipid being 4A3-SC7, (ii) a phospholipid; (iii) a cholesterol; and (iv) a polyethylene glycol-conjugated lipid (PEG-lipid), wherein the aerosol droplets have a mass median aerodynamic diameter (MMAD) from about 0.5 micron (μm) to about 10 μm and wherein the concentration of the polynucleotide in the droplets is between about 0.5 and 2 mg/mL.
Reference claim 1 is drawn to a lipid nanoparticle composition for delivering a polynucleotide to the lung cells in a subject wherein the lipid nanoparticle comprises:
(i) a polynucleotide;
(ii) a dendrimer ionizable cationic lipid;
(iii) an ethylphosphocholine at a molar percentage from about 20% to about 65%;
(iv) a phospholipid;
(v) a cholesterol; and
(vi) a polyethylene glycol-conjugated lipid,
wherein the dendrimer ionizable cationic lipid is
PNG
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536
1835
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Greyscale
and
wherein the lipid nanoparticle composition is an aerosol composition.
The differences are minor and obvious. The examined claims recite a droplet size while reference claims do not expressly disclose a composition form or droplet size. Also, the examined claims identify the polynucleotide as mRNA encoding DNAI1 protein, while reference claims are broadly directed to the polynucleotide. However, the modifications are obvious in view of the secondary references including Lockhart et al and Karve et al, and the knowledge available to one of ordinary skill in the art.
Thus, one of ordinary skill in the art would have been motivated to have selected one or more lipid compounds as taught by Angel et al for the lipid composition of Lockhart et al with a reasonable expectation of success. Lockhart et al teach compositions for aerosolization into the lungs of a subject comprising a polynucleotide being mRNA encoding DNAI1 protein and a lipid composition. Karve et al teach a similar composition in solution form for nebulization and provides guidance on the said droplet size and concentrations in mg/mL.
It would have been obvious to one of ordinary skill in the art to have looked in the art for specific polynucleotides as taught by Lockhart et al and droplet size as taught by Karve et al with a reasonable expectation of success.
Response to Arguments
Applicant's arguments filed 07/10/25 have been fully considered but they are not persuasive.
Applicant’s arguments with respect to Claims 120-122, 125-126, 130-132, 137-139 and 141-142 have been considered but are moot because the new ground of rejection does not rely on the prior rejections of record.
In particular, the arguments are essentially related to the limitations added to claim 120 by amendment. The said limitations are rejected by the modified rejection including new references.
Claims 120-121, 126, 130-132, 137-139 and 141-142 are rejected. Claims 127-128, 133-135, 140 and 143-149 are withdrawn.
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 Mina Haghighatian whose telephone number is (571)272-0615. The examiner can normally be reached M-F, 7-5 EST.
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/Mina Haghighatian/
Mina Haghighatian
Primary Examiner
Art Unit 1616