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 .
Election/Restrictions
Applicant's election with traverse of invention group I, claims 1-6, 12-14, 31, 37-38, 42, 44, 48-49, 68 in the reply filed on 10/14/2025 is acknowledged. The traversal is on the ground(s) that prior art does not teach special technical feature. This is not found persuasive because Veneziano et al. (Us20190156911) indeed teaches nanoparticle comprising lipid ([0417]) and mRNA to be delivered ([0430]), thus Veneziano et al. teaches the special technical feature. Furthermore, in the following 103 rejection, the special technical feature is also taught by Nakei et al.
The requirement is still deemed proper and is therefore made FINAL.
Claims 78, 80, 88-89, 110-111 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 10/14/2025.
Applicants further elected Lipid A (structure in claim 13) as special lipid, siRNA as specific rigid nucleic acid, GalNAC as specific targeting ligand. Claims 1-6, 13, 31, 37-38, 42, 44, 48 read on the elected species and are under examination; claims 12, 14, 49 (transgene is part of DNA, not part of RNA) and 68 do not read on the elected species and are withdrawn from consideration.
Claims 1-6, 12-14, 31, 37-38, 42, 44, 48-49, 68, 78, 80, 88-89, 110-111 are pending, claims 1-6, 13, 31, 37-38, 42, 44, 48 are under examination.
Priority
Acknowledge made that this application is national stage of international patent application of PCT/US2021/042033, filed on 07/16/2021; which claims priority from US provisional application 63/053274, filed on 07/17/2020 and US provisional application 63/194620, filed on 05/28/2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 03/27/2023, 11/19/2024 and 10/14/2025 is being considered by the examiner.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 48 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 48 contains the trademark/trade name “doggyboneTM”. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe the source of goods, accordingly, the identification/description is indefinite.
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 1-6, 13, 31, 42, 44 and 48 are rejected under 35 U.S.C. 103 as being unpatentable over Nakai et al. (US20210023008).
Determination of the scope and content of the prior art
(MPEP 2141.01)
Nakai et al. teaches a cationic lipid and lipid membrane structure (abstract). Nakai et al. teaches cationic lipid O-Ph-P4C2 (page 7, Table 1; page 13, Table 2, example 3).
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In one embodiment, the lipid membrane structure of the present invention is preferably lipid nanoparticles (LNP). The lipid membrane structure of the present invention may further contain other constituent components in addition to the cationic lipid of the present invention. Examples of other constituent component include lipid phospholipid (phosphatidylinositol, phosphatidylethanolamine, phosphatidylserine, phosphatidic acid, phosphatidylglycerol, phosphatidylcholine etc.), glycolipid, peptide lipid, cholesterol, cationic lipid other than the cationic lipid of the present invention, PEG lipid etc.), surfactant (e.g., 3-[(3-cholamidopropyl)dimethylammonio]propanesulfonate, sodium cholate salt, octylglycoside, N-D-gluco-N-methylalkanamides etc.), polyethylene glycol, protein and the like. The content of other constituent components in the lipid membrane structure of the present invention is generally 5-95 mol %, preferably 10-90 mol %, more preferably 30-80 mol % ([0137-0139]). While the content of the cationic lipid of the present invention to be contained in the lipid membrane structure of the present invention is not particularly limited, when the lipid membrane structure is used as the below-mentioned nucleic acid-introducing agent, it is generally an amount sufficient for introducing the nucleic acid. For example, the cationic lipid of the present invention is contained in 5-100 mol %, preferably 10-90 mol %, more preferably 20-70 mol %, of the total lipid (0140]). A nucleic acid can be introduced into a cell in vivo and/or in vitro by encapsulating the nucleic acid in the lipid membrane structure containing the cationic lipid of the present invention and contacting the lipid membrane structure with the cell. Therefore, the present invention provides a nucleic acid-introducing agent, containing the above-mentioned cationic lipid or lipid membrane structure of the present invention ([0143]). The nucleic acid-introducing agent of the present invention can introduce any nucleic acid into a cell. Examples of the kind of nucleic acid include, but are not limited to, DNA, RNA, chimera nucleic acid of RNA, DNA/RNA hybrid and the like. The type of the RNA that can be used in the present invention is not particularly limited, and can be selected as appropriate according to the purpose of use. For example, siRNA, miRNA, shRNA, antisense RNA, messenger RNA (mRNA) ([0144-0146]). One form of the lipid membrane structure encapsulating a nucleic acid is, for example, LNP encapsulating a nucleic acid by forming an electrostatic complex between the nucleic acid and a cationic lipid. The particle size of the lipid membrane structure of the present invention encapsulating a nucleic acid is not particularly limited, and is preferably 10 nm-500 nm, more preferably 30 nm-300 nm. The particle size can be measured by using a particle size distribution measuring device such as Zetasizer Nano (Malvern) or the like. The particle size of the lipid membrane structure can be appropriately adjusted by the method for preparing the lipid membrane structure ([0150-0151]). The concentration of the lipid membrane structure to be contacted with the cells is not particularly limited as long as the desired introduction of the nucleic acid into the cells can be achieved. The lipid concentration is generally 1-100 nmol/ml, preferably 10-50 nmol/ml, and the concentration of the nucleic acid is generally 0.01-100 μg/ml, preferably 0.1-10 μg/ml ([0160]). In on example, cationic lipid O-Ph-P4C2 is used, and cationic lipid/phospholipid/Chol/DMG- PEG2k = 60/10/30/3 ([0260], Table 5); siRNA is encapsulated with cationic lipid/Chol/DMG-PEG2k - 70/30/1.5 ([0266], Table 10).
Ascertainment of the difference between the prior art and the claims
(MPEP 2141.02)
The difference between the instant application and Nakai et al. is that Nakai et al. is not specific enough for anticipation.
Finding of prima facie obviousness
Rational and Motivation (MPEP 2142-2143)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to produce the instant invention.
Regarding claims 1-6, 13, 42 and 48, Nakai et al. teaches lipid nanoparticle comprising siRNA encapsulated by cationic lipid O-Ph-P4C2 (same as applicant’s specific lipid A and cationic lipid in claim 13) with particle size of 30nm -300nm.
Regarding claim 31, Nakai et al. teaches additional phospholipid (non-cationic lipid), Cholesterol, DMG- PEG2k (PEGylated lipid).
Regarding claim 44, Nakai et al. teaches lipid concentration 1-100 nmol/ml, preferably 10-50 nmol/ml, and the concentration of the nucleic acid is generally 0.01-100 μg/ml. For cationic lipid O-Ph-P4C2 (MW 1173.78), 1 nmol is 1.17 ug, 10 nmol is 11.7 ug, for 0.1 ug of RNA, the ratio is from 1.17/0.1 to 11.7/0.1 = 11.7/1 to 117/1, encompassing claimed range of about 15:1 or about 50:1.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. 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, especially in the absence of evidence to the contrary.
Claims 37-38 are rejected under 35 U.S.C. 103 as being unpatentable over Nakai et al. (US20210023008), as applied for the above 103 rejection for claims 1-6, 13, 31, 42, 44 and 48, in view of Jadhav et al. (US20100015218).
Determination of the scope and content of the prior art
(MPEP 2141.01)
Nakai et al. teaching has already been discussed in the above 103 rejection and is incorporated herein by reference.
Jadhav et al. teaches nanoparticles delivery of active ingredients such as siNA and miRNA by lipids (abstract, claim 1). In one embodiment, a composition of the invention further comprises a targeting ligand for a specific cell of tissue type. Non-limiting examples of such ligands include sugars and carbohydrates such as galactose, galactosamine, and N-acetyl galactosamine; hormones such as estrogen, testosterone, progesterone, glucocortisone, adrenaline, insulin, glucagon, cortisol, vitamin D, thyroid hormone, retinoic acid, and growth hormones; growth factors such as VEGF, EGF, NGF, and PDGF; cholesterol; bile acids; neurotransmitters such as GABA, Glutamate, acetylcholine; NOGO; inostitol triphosphate; diacylglycerol; epinephrine; norepinephrine; Nitric Oxide, peptides, vitamins such as folate and pyridoxine, drugs, antibodies and any other molecule that can interact with a receptor in vivo or in vitro. The ligand can be attached to any component of a formulated siNA composition of invention (e.g., cationic lipid component, neutral lipid component, PEG-DAG component, or siNA component etc.) using a linker molecule, such as an amide, amido, carbonyl, ester, peptide, disulphide, silane, nucleoside, abasic nucleoside, polyether, polyamine, polyamide, peptide, carbohydrate, lipid, polyhydrocarbon, phosphate ester, phosphoramidate, thiophosphate, alkylphosphate, or photolabile linker. In one embodiment, the linker is a biodegradable linker ([0176, 0206, 0213]).
Ascertainment of the difference between the prior art and the claims
(MPEP 2141.02)
The difference between the instant application and Nakai et al. is that Nakai et al. do not expressly teach targeting ligand. This deficiency in Nakai et al. is cured by the teachings of Jadhav et al.
Finding of prima facie obviousness
Rational and Motivation (MPEP 2142-2143)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the invention of Nakai et al., as suggested by Jadhav et al., and produce the instant invention.
One of ordinary skill in the art would have been motivated to include targeting ligand N-acetyl galactosamine (GalNAc) on surface of lipid nanoparticle because targeting ligand guides lipid nanoparticle to target a specific cell of tissue type as suggested by Jadhav et al. Since it is advantage to do so, it is obvious for one of ordinary skill in the art to include targeting ligand N-acetyl galactosamine (GalNAc) on surface of lipid nanoparticle and produce instant claimed invention with reasonable expectation of success.
Regarding claim 38, since applicants elected GalNAc (a single grouping of patentably indistinct species) as specific targeting ligand, each of GalNAc recited in claim 38 is patentably indistinct from each other, thus GalNAc reads on each of GalNAc in claim 38. Furthermore, applicants submitted in response to restriction that GalNAc read on claim 38. Therefore, the limitation of claim 38 is met.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. 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, especially in the absence of evidence to the contrary.
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 1-6, 13, 31, 37-38, 42, 44, 48 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4-5, 11, 14, 19, 21, 23, 25, 29 of copending Application No. 17632262 in view of Nakai et al. (US20210023008). The reference application teaches lipid nanoparticle comprising cationic lipid and DNA, in view of Nakai et al. teaching siRNA is another nucleic acid encapsulated by cationic lipid, it is obvious to prepare lipid nanoparticle comprising cationic lipid and siRNA and produce applicant’s claimed invention with reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
Claims 1-6, 13, 31, 37-38, 42, 44, 48 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 20-25, 31,36,43,46-47,51 and 55-56 of copending Application No. 17642314 in view of Nakai et al. (US20210023008). The reference application teaches lipid nanoparticle comprising ionizable lipid and nucleic acid, in view of Nakai et al. teaching siRNA is suitable nucleic acid encapsulated by cationic lipid O-Ph-P4C2, it is obvious to prepare lipid nanoparticle comprising cationic lipid O-Ph-P4C2 and siRNA and produce applicant’s claimed invention with reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
Claims 1-6, 13, 31, 37-38, 42, 44, 48 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 36, 38, 40, 65, 73-74 of copending Application No. 17913498 in view of Nakai et al. (US20210023008). The reference application teaches lipid nanoparticle comprising ionizable lipid and nucleic acid siRNA (in claim 38), in view of Nakai et al. teaching siRNA encapsulated by cationic lipid O-Ph-P4C2, it is obvious to prepare lipid nanoparticle comprising cationic lipid O-Ph-P4C2 and siRNA and produce applicant’s claimed invention with reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
Claims 1-6, 13, 31, 37-38, 42, 44, 48 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 20, 22, 24, 31, 38, 47-49, 51 of copending Application No. 17925404 in view of Nakai et al. (US20210023008). The reference application teaches lipid nanoparticle comprising ionizable lipid and nucleic acid siRNA (in claim 22), in view of Nakai et al. teaching siRNA encapsulated by cationic lipid O-Ph-P4C2, it is obvious to prepare lipid nanoparticle comprising cationic lipid O-Ph-P4C2 and siRNA and produce applicant’s claimed invention with reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
Claims 1-6, 13, 31, 37-38, 42, 44, 48 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 55-65, 68-69 of copending Application No. 18287751 in view of Nakai et al. (US20210023008). The reference application teaches lipid nanoparticle comprising ionizable lipid and nucleic acid siRNA (in claim 57), in view of Nakai et al. teaching siRNA encapsulated by cationic lipid O-Ph-P4C2, it is obvious to prepare lipid nanoparticle comprising cationic lipid O-Ph-P4C2 and siRNA and produce applicant’s claimed invention with reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
Claims 1-6, 13, 31, 37-38, 42, 44, 48 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 34-49, 51 of copending Application No. 18569623 in view of Nakai et al. (US20210023008). The reference application teaches lipid nanoparticle comprising lipid and nucleic acid siRNA (in claim 36), in view of Nakai et al. teaching siRNA encapsulated by cationic lipid O-Ph-P4C2, it is obvious to prepare lipid nanoparticle comprising cationic lipid O-Ph-P4C2 and siRNA and produce applicant’s claimed invention with reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
Claims 1-6, 13, 31, 37-38, 42, 44, 48 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7, 17-19, 27, 36, 38, 43, 47-48, 60, 64 of copending Application No. 18871840 in view of Nakai et al. (US20210023008) and Jadhav et al. (US20100015218). The reference application teaches lipid nanoparticle comprising lipid and nucleic acid siRNA (in claims 1, 17-19 and 27) but silent about particle size of LNP and targeting ligand, in view of Nakai et al. teaching siRNA encapsulated by cationic lipid O-Ph-P4C2 with particle size of 30nm-300nm, Jadhav et al. teaching targeting ligand N-acetyl galactosamine (GalNAc) on surface of lipid nanoparticle to target a specific cell of tissue type, it is obvious to prepare lipid nanoparticle with particle size at about 20 nm to about 75 nm comprising cationic lipid O-Ph-P4C2 and siRNA and produce applicant’s claimed invention with reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
Claims 1-6, 13, 31, 37-38, 42, 44, 48 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 12263228 in view of in view of Nakai et al. (US20210023008). The reference application teaches lipid nanoparticle comprising lipid and nucleic acid siRNA (in claim 4), in view of Nakai et al. teaching siRNA encapsulated by cationic lipid O-Ph-P4C2, it is obvious to prepare lipid nanoparticle comprising cationic lipid O-Ph-P4C2 and siRNA and produce applicant’s claimed invention with reasonable expectation of success.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JIANFENG SONG. Ph.D. whose telephone number is (571)270-1978. The examiner can normally be reached M-F 8-5.
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/JIANFENG SONG/Primary Examiner, Art Unit 1613