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 07/14/25 and an IDS filed on 05/02/25. Claims 1, 3, 8, 15 and 17-23 have been amended, no new claims have been added and claims 2, 4-5, 14, 16, 24 and 28-31 have been canceled. Accordingly, claims 1, 3, 6-13, 15, 17-23 and 25-27 remain pending and 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Rejections and/or objections not reiterated from the previous Office Action are hereby withdrawn.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 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 1, 3, 6-13, 15, 17-23 and 25-27 are rejected under 35 U.S.C. 103 as being unpatentable over Lockhart et al (US 20190117796) in combination with Karve et al (WO 2020106946), Angel et al (WO 2016131052) and Siegwart et al (US 20170121279).
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. Disclosed are polyribonucleotides that 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 teach a method for treating a subject having or at risk of having primary ciliary dyskinesia, the method comprising administrating to the subject a composition that comprises a nucleic acid construct that encodes dynein axonemal intermediate chain 1 protein or a variant thereof, which nucleic acid construct includes codons that provide for heterologous or enhanced expression of the dynein axonemal intermediate chain 1 protein or a variant thereof within cells of the subject, thereby treating the subject having or at risk of having primary ciliary dyskinesia (See [0006]).
Lockhart et al disclose that the term “subject,” refers to a human, an animal, such as a horse, a rabbit, and various other animals (See [0044]).
At least 21 mutations in the DNAI1 gene have been found to cause primary ciliary dyskinesia. DNAI1 gene mutations result in an absent or abnormal intermediate chain 1 (See [0062]).
Lockhart et al teach and claim a pharmaceutical formulation comprising a polynucleotide that is at least 80% homologous to nucleic acids 1-1,000 of SEQ ID NO: 15, wherein said polynucleotide is an mRNA; wherein fewer than 15% of nucleotides within said polynucleotide are nucleotide analogues; and wherein said pharmaceutical formulation comprises a cationic lipid, a fusogenic lipid, a cholesterol and a polyethylene glycol (PEG) lipid (See [0156] and claims 1-4 and 7-9).
Lockhart et al teach a composition comprising a polyribonucleotide for treating a subject having or at risk of having primary ciliary dyskinesia, wherein the composition comprises at least one additional nucleic acid construct that encodes a protein selected from the group consisting of: coiled-coil domain containing 39 (CCDC39), coiled-coil domain containing 40 (CCDC40), coiled-coil domain containing 65 (CCDC65), cyclin O (CCNO), dynein axonemal heavy chain 5 (DNAH5), etc, (See [0060]).
Lockhart et al teach that encapsulation of polynucleotides with formulations that can increase the endocytotic uptake can increase the effectiveness of the said composition. To overcome this challenge, in some cases, the composition comprises a nucleic acid construct, a vector, or an isolated nucleic acid encoding dynein axonemal intermediate chain 1 (DNAI1), wherein the nucleic acid construct comprises a complementary deoxyribonucleic acid encoding dynein axonemal intermediate chain 1, which composition is formulated for administration to a subject.
Lockhart et al teach a composition comprising an engineered polyribonucleotide which can be encapsulated or formulated with a pharmaceutical carrier. The formulation may be nanoparticles, PLGA microspheres, lipidoids, lipoplex, liposome, polymers, cationic lipids, etc, (See [0148] and [0150]).
It is also disclosed that the engineered polynucleotide in a composition may be at least 0.05%, 9%, or 10%. The encapsulation efficiency of the modified mRNA in the PLGA microsphere may be at least 96%, or at least 99% (See [0151] and [0209]).
The disclosure provides formulations that can be employed for effective delivery and translation of polyribonucleotide compositions to a subject (See [0157]).
Lockhart et al teach that the said lipidoid or lipid nanoparticle can comprise one or more lipids in various ratios. A nanoparticle can include at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 lipids or another suitable number of lipids. A nanoparticle can be formed of any suitable ratio of lipids 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 (See [0155]-[0156]).
Lockhart et al further disclose that an engineered polyribonucleotide can be encapsulated in a lipidoid formulation. A lipidoid formulation can be a lipid, phospholipids, and others, such as cholesterol, DOPE, DOPC or DSPC and/or PEGylated lipids or any other lipid useful for preparing lipoplexes. The composition containing may contain about 40-60% lipidoid, about 40-60% cholesterol, and about 5-10% PEG-lipid (in percent by weight, based on the total weight of the composition). (See [0207]-[0208] and claim 7).
It is stated that the modified nucleotide compositions comprise less than 1 mg/mL of the polynucleotide (See Table 6).
The polydispersity index PDI of the nanoparticle formulation comprising the modified mRNA can be between 0.03 and 0.15 (See [0156]).
For administration by inhalation, the active compounds can be in a form of an aerosol, a mist, or a spray and may be conveniently delivered in the form of an aerosol spray presentation from pressurized packs or a nebulizer (See [0231] and [0245]).
It is further disclosed that a nucleic acid construct encoding the DNAI1 gene sequence, is prepared and after diluting it in 5% glucose (final concentration), the RNA and jetPEI solutions are combined/mixed at a ratio of 1:1 with a final N/P ratio of 8. The mRNA is then administered by nebulizing (See [0245]).
Lockhart et al disclose that in some cases the composition, vector, or a nucleic acid construct comprising a nucleic acid construct encoding dynein axonemal intermediate chain 1 is provided, wherein fewer than 15%, or fewer than 2.5% of the nucleotides encoding DNAI1 are nucleotide analogues such as pseudouridine or 1-methyl pseudouridine (See [0103] and [0144]).
Lockhart et al lack specific disclosure on the average droplet sizes or the flow rate for nebulization. These are known in the art as taught by Karve et al. Lockhart et al also is silent with regard to the lipid composition comprising DODAP or the core-repeating unit-terminating group (D-I). These are known in the art as taught by Angel et al and Siegwart et al.
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 including PEG-modified phospholipids. The non-cationic lipid may be a phospholipid such as DOPE (See [0015] and [0142]).
It is disclosed that the said cationic lipid may be DODAP, DOTAP, etc, (See [0134]-[0138]). The lipid delivery system may also comprise a cholesterol-based lipid (See [0130] and [0141]).
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 Table 9, Karve et al disclose MMAD, GSD, FPF, Mass Balance and Delivered Dose Results (VMT nebulizer 1)
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As can be seen, the MMAD and GSD values are well within the claimed values of examined claims 109 and 143-144.
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)).
Angel et al teach nucleic acid products and a method of their administration (See Title and Abstract).
The said composition contains one or more lipids that enhance uptake of RNA by cells; optionally, wherein the one or more lipids are selected from the lipids including:
1,2-dimyristoyl-3-trimethylammonium-propane (14:0 TAP),
1,2-dimyristoyl-sn-glycero-3-ethylphosphocholine (14:0 EthylPC),
1,2-dioleoyl-3-trimethylammonium-propane (DOTAP / 18:1 TAP),
1,2-dioleoyl-3-dimethylammonium-propane (DODAP / 18:1 DAP), etc, (See pages 16-17 and Table 1 and claims 20 and 30).
Routes of administration for the said formulation includes inhalation and injection (See page 19, lines 15-18). The said formulations can be administered to treat a respiratory condition (See Page 52, lines 3-8).
Siegwart et al teach dendrimers with cationic groups and lipophilic groups formulated in compositions which contain a nucleic acid and one or more helper excipients (See abstract).
Disclosed is a dendrimer of the formula: Core-(Repeating Unit)n-Terminating Group (I)
wherein the core is linked to the repeating unit and wherein:
the core has the formula:
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97
613
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wherein:
X3 is —NR6—, wherein R6 is hydrogen, alkyl(C≦8), or substituted alkyl(C≦8),
R3 and R4 are each independently amino, alkylamino(C≦12), dialkylamino(C≦12), or a substituted version of either of these groups; or a group of the formula: —(CH2CH2N)e(Rc)Rd;
wherein:
e is 1, 2, or 3;
Rc and Rd are each independently hydrogen, alkyl(C≦6), or substituted alkyl(C≦6);
c and d are each independently 1, 2, 3, 4, 5, or 6; or
wherein the repeating unit comprises a degradable diacyl and a linker;
the degradable diacyl group has the formula:
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229
804
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wherein:
A1 and A2 are each independently —O—, wherein:
Y3 is alkanediyl(C≦12), alkenediyl(C≦12), arenediyl(C≦12),
R9 is alkyl(C≦8) or substituted alkyl(C≦8);
and
the terminating group has the formula:
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154
606
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wherein:
Y4 is alkanediyl(C≦18) or an alkanediyl(C≦18),
and
R10 is hydrogen (See at least [0007], [0237-[0256] and claims).
The nucleic acid is a short interfering RNA, a messenger RNA (mRNA), etc (See [0217]-[0219]).
Siegwart et al teach that the helper lipid is a PEG lipid or a phospholipid, such as 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), or 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE). The phospholipid and the dendrimer are present in a molar ratio from about 10:1 to about 1:20 (See [0220]-[0230] and [0274]-[0275]).
It is stated that a pharmaceutical acceptable carrier is a solvent or solution and the composition is formulated for administration: orally, intraarterially, via inhalation, etc, (See [0234]).
Siegwart et al disclose in Example 10, evaluation of dendrimer nanoparticles for delivery of mRNA. It is disclosed that compositions containing either DSPC, DOPE, or no phospholipid and PEG-DHD as the PEG-lipid with the molar ratios of lipid (or dendrimer):cholesterol:phospholipid:PEG-lipid being 50:38.5:0(10):2 and a weight ratio of dendrimer to nucleic acid (mRNA) of 5, 10, 20, 30, or 40 to 1 and two different doses: a 50 ng dose and a 100 ng dose were tested. The delivery used a nanoparticle composition with 20:1 ratio N/P and DSPC as the phospholipid and PEG-DHD as the PEG-lipid (See [0499]).
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 Angel et al, Siegwart et al and Karve et al with that of Lockhart et al to arrive at the instant invention. It would have been obvious to do so because Lockhart et al and Karve et al teach methods of treating a lung disorder including primary ciliary dyskenisia or cystic fibrosis by administering via a nebulizer a formulation comprising a lipid encapsulated polynucleotide such as mRNA for effective delivery and administration of the active agents to the subject. While Lockhart et al teach nebulization as an effective mode of delivery of the said formulations, they do not expressly disclose nebulization flow rates and droplet sizes. Thus, one of ordinary skill in the art wishing to follow Lockhart et al’s guidance would have been motivated to look in the art for suggestions on the said flow rate and droplet sizes to optimize the said method. Karve et al teach a similar delivery system wherein the lipid encapsulated nucleic acids are delivered via a nebulizer and provide guidance on the suitable flow rates and droplet sizes for an effective treatment and delivery to the pulmonary system.
Accordingly, 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.
It also 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 Angel et al and Siegwart et al with the combined teachings of Karve et al and Lockhart et al to arrive at the instant invention. It would have been obvious to do so because Angel et al teach that a nucleic acid drug is formulated with one or more lipids to enhance uptake of the nucleic acid drug by cells, and the lipids are selected from lipids including 14:0 TAP, 14:0 EPC, DODAP, etc. Thus, one of ordinary skill in the art would have been motivated to select one or more effective lipids listed by Angel et al because it is disclosed that the said lipids enhance delivery of nucleic acids to the cells or organs. Siegwart et al teach delivering nucleic acids including mRNA to target cells via liposomes of different lipids including those of the structural formula of core-repeating unit-terminating group and other phospholipids and helper lipids.
Accordingly, 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.
In addition, all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention.
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 1, 3, 6-13, 15, 17-23 and 25-27 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-28 of U.S. Patent No. 12,337,068 in view of Cheng et al (WO 2020051220) and Angel et al (WO 2016131052). 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 Cheng et al and Angel et al.
Examined claim 1 is drawn to a method for treating a subject having or suspected of having a lung disorder resulting from aberrant expression or activity of a gene or a polypeptide, the method comprising: administering at a nebulization flow rate of at least 0.2 mL/minute to said subject by inhalation aerosol droplets having an average droplet size from about 0.5 micron (um) to about 10 um, the aerosol droplets comprising a lipid composition comprising at least five components and a heterologous polynucleotide assembled with the lipid composition, with a molar ratio of nitrogen in said lipid composition to phosphate in said polynucleotide (N/P ratio) of no more than about 20:1, wherein the lipid composition comprises: 1,2-Dioleoyl-3-dimethylammonium-propane (18:1 DODAP),; a phospholipid; a sterol; a polyethylene-lipid (PEG-lipid); and a compound having the structural formula: Core-Repeating Unit-Terminating Group (D-I), or a pharmaceutically acceptable salt thereof.
Reference claim 1 is drawn to a method for selectively delivering an mRNA to the lungs of a subject, wherein the method comprises nebulizing a liquid pharmaceutical composition which comprises lipid nanoparticles (LNPs) comprising said mRNA to generate an aerosolized pharmaceutical composition, and administering the aerosolized pharmaceutical composition to the subject, wherein the LNPs comprise an ionizable lipid, a phospholipid, a PEG-lipid, and a sterol, wherein the LNPs have an mRNA integrity of between 75% and 99%, and wherein the aerosolized pharmaceutical composition comprises aerosol particles having: (a) a mass median aerodynamic diameter (MMAD) of from 1 μm to 10 μm,(b) a geometric standard deviation (GSD) of from 1 to 5, and (c) a fine particle fraction (FPF) percent of at least 50%, wherein administering the aerosolized pharmaceutical composition to the subject results in minimal amounts of mRNA in the blood, liver, and spleen of the subject.
Reference claim 10 is directed to the method of claim 1, wherein the ionizable lipid is a compound having the structural formula:Core−Repeating Unit−Terminating Group (D-I),
or a pharmaceutically acceptable salt thereof, wherein:
the core is linked to two to six repeating units by removing two to six hydrogen atoms from the core and replacing the hydrogen atoms with the repeating units; wherein:
the core has the formula:
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96
595
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wherein, in Formula (D-IV):
X3 is —NR6—, —O—, or optionally substituted alkylaminodiyl(c≤8); wherein R6 is hydrogen, alkyl(c≤8), or substituted alkyl(c≤8),
R3 and R4 are each independently amino, optionally substituted alkylamino(c≤12), or optionally substituted dialkylamino(c≤12);
wherein:
c and d are each independently 1, 2, 3, 4, 5, or 6;
the repeating unit comprises a degradable diacyl group of the formula:
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229
783
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wherein, in Formula (D-VII):
A1 and A2 are each independently —O—;
Y3 is —CH2CH2—; and
R9 is —CH3; and
the terminating group has the formula:
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wherein, in Formula (D-VIII):
Y4 is alkanediyl(c≤18) or an alkanediyl(c≤18); and
R10 is hydrogen.
The differences are including examined claim being directed to a method of treating a lung condition, while reference claims are directed to a method selectively delivering the compositions to a subject’s lung and in the combination of compounds of the lipid composition. While examined claims require DODAP, reference claim 1 requires comprising an ionizable lipid, a phospholipid, a PEG-lipid, and a sterol. Reference claims 11, 13 and 15 recite specific cationic lipids and other lipids such as phospholipids. These compounds are added by way of dependent claims in the examined Application. However, as taught by Cheng et al and Angel et al, these modifications would have been obvious. Cheng et al teach compositions which shown preferential targeting or delivery of a nucleic acid composition to a particular organ, wherein the composition comprises a steroid or sterol, an ionizable cationic lipid, a phospholipid, a PEG lipid, and a permanently cationic lipid, Cheng et al teach that the said delivery to the lung treats lung conditions. Angel et al also teach that the delivery lipid formulation may comprise one or more lipid compounds including 14:0 TAP, 14:0 EPC, phospholipids, DODAP, etc. 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 Cheng et al with a reasonable expectation of success.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
1- Hefesha et al (US 20180263907).
Hefesha et al teach lipid particles comprising at least one cationic lipid, at least one water-soluble therapeutically effective compound and RNA, and pharmaceutical compositions comprising such particles for delivery to target cells (See title, abstract and [0009]).
It is disclosed that the said particles comprise at least one helper lipid, including 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine (DOPE), cholesterol (Chol), 1-palmitoyl-2-oleoyl-sn-glycero-3phosphocholin (POPC) and/or 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), preferably DOPC, DOPE and/or Chol. The at least one cationic lipid comprises 1,2-dimyristoyl-sn-glycero-3-ethylphosphocholine (DMEPC), 1,2-di-O-octadecenyl-3-trimethylammonium propane (DOTMA) and/or 1,2-dioleoyl-3-trimethylammonium propane (DOTAP), preferably DOTAP and/or DOTMA (See [0017]-[0018]).
Suitable cationic lipids comprise one cationic charge and include 1,2-dimyristoyl-sn-glycero-3-ethylphosphocholine (DMEPC), 1,2-di-O-octadecenyl-3-trimethylammonium propane (DOTMA) and/or 1,2-dioleoyl-3-trimethylammonium propane (DOTAP), 1,2-dimyristoyl-3-trimethylammonium propane (DMTAP), etc, (See [0093]).
The particles have an average diameter in the range of from about 50 nm to about 1000 nm (See [0019]).
The said RNA maybe mRNA (See [0107]).
Typical systemic routes of administration include administration by introducing the agent directly into the vascular system or oral, pulmonary, or intramuscular administration wherein the agent is adsorbed, enters the vascular system, and is carried to one or more desired site(s) of action via the blood (See [0162]).
2- Mautone et al (EP 0607118).
Mautone et al teach a phospholipid delivery system and an aerosol delivery of therapeutically active substances which can be suspended in aqueous media to serve as a drug delivery system (See abstract). The system is a complex mixture of lipids, proteins and carbohydrates (See [0005]).
Mautone et al disclose that the diameter of aerosol particles was determined in a cascade impactor. Flow through the impactor was the same as aerosol flow from the nebulizer, 200 microliters/second (i.e. 0.2 mL/s). About 95% of the particles were equal to or less than 4 microns (See [0030]).
It is also claimed that the aerosolized droplets have a mean aerodynamic diameter in the range of from 1 to 50 microns (See claim 13).
Response to Arguments
Applicant’s arguments with respect to Claims 1-31 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 the claims by amendment. The said limitations are rejected by the modified rejection including new references.
Claims 1, 3, 6-13, 15, 17-23 and 25-27 are rejected.
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