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 .
Notice of Pre-AIA or AIA Status
DETAILED ACTION
Status of the Claims
Claims 1-29, 49, and 51-53 are cancelled. Claims 54-56 are new. Claims 30-48, 50 and 54-56 are pending and under examination.
Priority
This application is a national stage entry of PCT/US2022/016902 filed on 2/18/2022, which claims priority from US provisional applications 63/191,655 filed on 5/21/2021, 63/182,428 filed on 4/30/2021 and 63/151,523 filed on 2/19/2021.
Information Disclosure Statement
The information disclosure statements filed on 11/15/2023, 12/29/2023 and 5/19/2025 have been considered by the examiner.
Election/Restriction
Applicant's election with traverse of group II in the reply filed on 11/7/2025 is acknowledged. The traversal is on the ground(s) that Brader does not break unity since the claims address an unrecognized problem. This is not found persuasive because Brader does teach the use of various techniques of applicant’s claims including low temperatures, pH values near 7, buffers, chelators and antioxidants with its compositions that include lipid nanoparticles of ionizable lipids with tertiary amines and mRNA/polynucleotides. The amount of adduct impurities is the occurrence of treating such compositions in these ways. Brader also recognizes the use of these techniques to reduce impurities produced in the composition, and thus, is toward the problem that applicant addresses in the claims.
The requirement is still deemed proper and is therefore made FINAL.
It is noted that applicant has amended claims of other groups to be part of the method of group II or cancelled claims of other groups. Thus, no claims are withdrawn at this time.
Claim Objections
Claims 30-48 are objected to for appearing before the claim(s) on which they depend. Dependent claims need to appear after the claim on which they depend on.
Claims 45 and 46 are objected to for “aminoxy”, which is appropriately spelled as “aminooxy”.
Claims 30, 42, 44, 46, 50, 54, 55 and 56 are objected to for “selected from…and….” And “one or more of….and….” which more appropriately use “or” as the conjunction to connect the alternatives as the claim does not follow the structure of “selected from the group consisting of….and…”. In events were combinations are allowed, applicant may end the claim with “or a combination thereof”. Thus, applicant could opt to use “selected from the group consisting of ….and…” language for such groups or alternatively can amend to say “selected from…or…” or “one or more of….or….”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 45 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. Claim 45 includes an “aminoxy functionality-containing scavenging agent”, which is meant to cover a genus of compounds/derivatives with an aminooxy (-O-NR2, -O-NH2) group that also have scavenging activity. Paragraph 765 teaches “(O-(2,3,4,5,6-Pentafluorobenzyl)hydroxyl amine hydrochloride) (PFBHA), methoxyamine (e.g., methoxyamine hydrochloride), benzyloxyamine (e.g., benzyloxyamine hydrochloride), ethoxy amine (e.g., ethoxyamine hydrochloride), 4-[2-(aminooxy)ethyl]morpholine dihydrochloride, butoxyamine (e.g., tert-butoxyamine hydrochloride)” as species that would be aminooxy scavenging agents. Paragraph 899 provides for amino-oxy PEG as a scavenger. There is written description for these species, but there is no written description for other aminooxy group containing compounds that would also be capable of functioning as scavengers. Other compounds of this genus could have a wide variety of compounds for the aminooxy group to be attached to as well as various alkyl or aryl groups that could be attached to the nitrogen atom. There is no definition of particular structures associated with scavenging activity or sufficient number of species of compounds with scavenging activity with aminooxy groups in the specification that would cover the entire possible genus (e.g. various other polymers or compound structures that might also carry some form of aminooxy groups). Without description of all the possible compounds of various structures in this genus that can also act as scavengers, the applicant does not show sufficient ownership of the compounds in this genus. However, as noted applicant does describe some species of more particular structure that are known to function as scavengers. Applicant may provide a Markush group of such described compound species to obtain a claim that has adequate description.
Claim Rejections - 35 USC § 112(b)
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.
Claims 30-48, 50 and 54-56 are 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.
Claims 50, 35, and 36 are indefinite for the recitations of “less than about 10% of the polynucleotide in the composition is in the form of ionizable lipid-polynucleotide adduct impurity” and “less than about 5% or (1%) of the mRNA in the composition is in the form of the ionizable lipid-polynucleotide adduct impurity” as they do not dictate the conditions time and possibly temperature of storage at which point the composition was checked for these adduct impurities. For example, all the compositions might fit these percentages after very short storage times (1 minute, 5 minutes) or even claimed compositions with treatment can be outside the range under very long storage times (e.g. 2 years or more). Additionally, different types of “treating” can provide different results, and thus, it would be unclear if what effect is established for one treatment type will be applicable to another treatment type (e.g. what happens to adducts with specific chelator like EDTA vs. storage at 4 degrees C vs. adjusting pH to 7 vs Tris buffer). Thus, it is unclear how this limitation should be considered for the scope of the claims. For the purpose of compact prosecution, if the prior art teaches treating a composition by techniques provided by applicant (e.g. changing temperature, changing pH, adding buffers, or adding chelators and/or reducing agents (antioxidants) and/or sequestering agents, then it will be considered as being capable to provide this effect on adduct impurities. Applicant should consider providing a time and any relevant conditions in which the compositions were checked for adduct-impurities that would be comparable.
Claims 31-34, 37-48, and 54-56 are rejected as being dependent on indefinite claims.
Claim 45 is indefinite as claim 54 provides “treating with a scavenging agent before combining the ionizable lipid and polynucleotide”, but claim 45, which depends on claim 54, provides for treating with an aminoxy functionality containing scavenging agent without any requirement for “before combining”. It is unclear if this limitation is supposed to place an additional limitation to the “treating with a scavenging agent..” recited in claim 54 or if it is meant to be a separate and new limitation to the group that is presented in claim 54, which isn’t bound to the “before combining” part of the limitation. For the purpose of compact prosecution, the examiner will consider the limitation as not being bound to “before combining”.
Claim 46 is rejected for being dependent on an indefinite claim.
Claim 45 is indefinite for aminoxy functionality containing scavenger agent as the applicant does not define all the other structure that can be incorporated with the aminoxy
Claim 54 recites the limitation "the buffer" in the claim without a prior recitation of “a buffer” in the claim or claim 50, on which it depends. Buffer is an additional component and not a property/characteristic of the composition. There is insufficient antecedent basis for this limitation in the claim.
Claims 41-46 and 56 are rejected as being dependent on an indefinite claim.
Claim 55 is indefinite as the claim depends on itself. It is unclear what claim the claim should actually be dependent on. The contents in the claim beginning with “the” will also lack antecedent basis as the claim does not refer to a claim where these items are introduced. For the purpose of compact prosecution, the examiner will consider the claim as being dependent on claim 54.
Claim Rejections – 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 30-33, 35-36, 38-41, 43-44, 47-48, 50, 54, and 56 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Brader US 20190336452A1 as evidenced by Packer et al (Nature communications, Nov 2021, https://doi.org/10.1038/s41467-021-26926-0).
Recitation of “less about about 50 ppm” would include down to zero for the given item.
Recitation of less than about 10%, (5% or 1%) will include down to zero for the given item.
In regards to the wherein clause “wherein less than about 10% of the polynucleotide in the composition is in the form of ionizable lipid-polynucleotide adduct impurity, as measured by reverse phase ion pair high performance liquid chromatography (RP-IP HPLC)”, this provides a characteristic of the formulation as found by a technique, but does not impart a step in the process.
Since the composition of Brader include ionizable lipids (including teachings of species in the claims) and mRNA, they are capable of forming ionizable lipid-mRNA (polynucleotide) adducts such as aldehyde-polynucleotides or lipid aldehydes. Brader teaches lipid nanoparticles with a plurality of lipid nanoparticles and a stabilizing agent that mitigates the degradation of the LNPs or a subpopulation thereof (abstract). Brader teaches the lipid nanoparticles include therapeutics like RNA (abstract). Brader teaches each of the LNPs comprises an ionizable lipid and a structural lipid, and the stabilizing agent comprises a surfactant, a cryoprotectant, a chelator, an antioxidant, or any combination thereof (claim 1 of Brader). Brader teaches liposomes and lipoplexes (paragraph 259). Brader teaches preservatives that can be included such as antioxidants (reducing agents), chelating agents, alcohol preservatives, acidic preservatives and others (paragraph 487). Brader teaches mRNA included with the LNP (paragraph 493). Brader teaches lipids with a central amine group such as in formula I (paragraphs 222-224 and also paragraphs 204-221). R4 is allowed to be C1-C6 alkyl that can be substituted (paragraph 189). Paragraph 233 provides for compounds including :
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. These lipids are noted as being cationic or ionazable (paragraph 232). Brader teaches 1-methyl-pseudouridine and other useful nucleotides (paragraphs 335 and 350). Brader teaches the formulation being substantially free of impurities with less than 1% and less than 0.5% of impurities (claim 88 of Brader). Brader teaches “impurities include aggregates of the phase-separated structure lipid (e.g., cholesterol crystals) and aggregates of the phase-separated ionizable lipid (e.g., ionic lipid microglobules)” (paragraphs 44-45). Brader teaches “A method of screening for a stabilizing agent for mitigating degradation of lipid nanoparticles in a lipid nanoparticle (LNP) formulation, the method comprising:
(a) providing a first LNP formulation absent a stabilizing agent and a second LNP formulation comprising the stabilizing agent, wherein the first and second LNP formulations are identical except for the stabilizing agent and each of the LNPs in the first and second LNP formulations comprises an ionizable lipid and a structural lipid; (b) determining the degradation of the LNPs in the first and second LNP formulations upon storage at about −20° C. or lower for a period of time or upon one or more freeze/thaw cycles; and (c) selecting the stabilizing agent if the degradation of the second LNP formulation is less than that of the first LNP formulation (Claim 131 of Brader). Brader teaches “chemical stability is improved by including a chelator (such as DTPA) in the LNP formulation (either liquid or lyophilized) that is stored at about 4° C. or higher. See, e.g., FIG. 3. In some embodiments, including a chelator improves chemical stability of a lyophilized LNP formulation containing a nucleic acid (such as an mRNA) that has about 900 nucleotides in length or shorter. Without wishing to be bound by the theory, the chelator prevents the nucleic acids from degradation via reacting with metal ions such as Cu2+ and Fe2+.” (paragraph 142). Thus, it appears that adjusting tempature and adding chelators are seen as allowing for better chemical stability in teachings of Brader. Brader teaches “DTPA improvies mRNA (with a length of 2000 nucleotides) stability at various storage temperatures for 2 months (PBS, pH 7.4)” (paragraph 102, also see paragraph 103, paragraph 142 provides DTPA as a chelator). Thus, here pH of a composition with mRNA is adjusted to 7.4, it’s in a buffer (PBS) and a chelator is included to increase stability. Paragraph 103 provides “effects of various antioxidants (antioxidants are reducing agents) on chemical stability of LNP formulations stored at 40° C., wherein LNP formulation (mRNA with a length of 2000 nucleotides, Tris, sucrose, pH 7.4) with 1 mM DTPA (the chelator) is used as control”. Paragraph 577 provides for lipid particles with RNA in a buffer with Tris and EDTA that is at pH 7.5. A combination of treatments as provided in applicant’s claims is provided in these examples. Brader teaches “chelator comprises diethylenetriamine pentaacetic acid (DTPA), ethylenediaminetetraacetic acid (EDTA), iminodisuccinic acid, polyaspartic acid, ethylenediamine-N,N′-disuccinic acid (EDDS), methylglycinediacetic acid (MGDA), L-glutamic acid N,N-diacetic acid (GLDA), or a salt thereof. For example, the antioxidant comprises ascorbic acid, citric acid, malic acid, methionine, monothioglycerol, phosphoric acid, potassium metabisulfite, alpha-tocopherol, or any combination thereof (paragraphs 179-180). Example 2 of Brader provides for stability of frozen LNP formulations with mRNA when in a Tris buffer (paragraphs 578-580). Brader teaches effect of cryoprotectants on frozen mRNA-LNP (examples 3-5). Brader teaches “ isotonic formulations of propylene glycol (PG) and glycerol in 20 mM Tris buffer, pH 7.4 are identified as potentially improved formulation vehicles and warrant further evaluation” (paragraph 580). Brader teaches formulations with buffers including Tris buffers (paragraphs 589-594). Brader teaches citric acid as an antioxidant (paragraph 41).
Thus, as examples and teachings of Brader anticipate the treating of mRNA and ionizable lipids in forming or with after formed lipid nanoparticles with buffers including Tris, pH adjustment including to 7.4, temperature control (freezing) and stabilizing agents including chelating agents and reducing agents (antioxidants) in order to stabilize the composition from forming impurities it will lead to the reduced amounts of adducts or other impurities as dictated in the claims. As Brader provides for such treatments of the claimed compositions and recognizes down to less than 0.5% impurities, it is anticipated to have the same effects to reduce adducts and other impurities mentioned in the claims. Note in MPEP 2112 – “There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003) (rejecting the contention that inherent anticipation requires recognition by a person of ordinary skill in the art before the critical date and allowing expert testimony with respect to post-critical date clinical trials to show inherency); see also Toro Co. v. Deere & Co., 355 F.3d 1313, 1320, 69 USPQ2d 1584, 1590 (Fed. Cir. 2004) ("[T]he fact that a characteristic is a necessary feature or result of a prior-art embodiment (that is itself sufficiently described and enabled) is enough for inherent anticipation, even if that fact was unknown at the time of the prior invention.")” In this instance, formation of the adducts/impurities and the decrease thereof is inherent to the tertiary amine-lipids with the mRNA and the use of stabilizing techniques like freezing (lowering temperature), buffers, pH value adjustment to values around 7.4-7.5, antioxidants (reducing agents) and chelators that are all taught for use with such components and compositions as provided by Brader’s examples, claims and disclosure and its additional teachings that such methods stabilize the product to not form as many impurities. Packer et al evidences that loss of mRNA activity in lipid nanoparticle systems is the result of reactions that occur between the mRNA and the lipids (see Discussion of Packer, also Results). The discussion of Packer also evidences that the adducts were missed by use of other analysis techniques (Discussion of Packer).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 34, 37, 42, 45 and 55 in addition to claims 30-33, 35-36, 38-41, 43-44, 47-48, 50, 54, and 56 are rejected under 35 U.S.C. 103 as being unpatentable over Brader US 20190336452A1.
Brader teaches the claims as discussed above.
Brader does not teach an embodiment where there is N1-methyl-pseudoridine in the mRNA, where there is a halide or halogen group that could form an alkyl halide-polynucleotide, one that uses potassium metabisulfite, or where there is an aminoxy functionality-containing scavenging agent.
Brader teaches 1-methyl-pseudouridine as a nucleic acid that is useful (paragraph 335) and alternative uracil such as N1-methyl-pseudouridine (paragraph 350). Brader teaches various nucleobases that have chloro (paragraph 352), bromo (paragraph 354) or fluoro (paragraph 354) groups allowing for halogens to be present. Brader also allows alkyl groups to be substituted with halogen groups (paragraph 241). Brader teaches potassium metabisulfite as an antioxidant preservative (paragraph 487 and claim 71 of Brader). Brader teaches a surfactant that is myristamine oxide (an aminoxy compound) (paragraph 181) and cryoprotectant including trimethylamine N-oxide (paragraph 15).
One of ordinary skill in the art before the time of filing would have used the teachings of Brader to provide for other components that they teach for making the mRNA or the stable formulations allowing one of ordinary skill in the art a reasonable expectation of success in making more stable formulations of polynucleotides and ionizable tertiary amine lipids. In addition, one of ordinary skill in the art would be able to optimize stabilizing agents and conditions to reduce impurities caused by free radical and oxidation activity to low levels as recognized by Brader through its teachings. This would allow formulations of the applicant’s claims having similar functionality.
Claims 30-45, 47-48, 50, 54, 55 and 56 are rejected under 35 U.S.C. 103 as being unpatentable over Brader US 20190336452A1 and Chen US 20150166465A1.
Brader teaches the claims as discussed above.
Brader does not teach all the reducing agents or scavenging agents of applicant’s claims.
Chen teaches an improved lipid formulation with cationic lipid of formula I, a tertiary amine (abstract). Chen teaches other antioxidants such as lipoic acid, uric acid, glutathione and others (paragraph 76). Chen teaches RNAs (paragraphs 3 and 4). Chen teaches DTT, or other reducing agent (paragraph 332). Chen teaches antioxidant (e.g. a radical scavenger) (paragraph 76).
One of ordinary skill in the prior art before the time of filing would have sought out other antioxidants/reducing agents of the prior art to preserve and stabilize its polynucleotide/lipid formulations with a reasonable expectation of success as each reference recognizes the use of antioxidants in formulations with ionizable lipids and RNA molecules. Brader provides the basis for using such compounds as stabilizers to protect against increased impurities.
Obviousness-type 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 30-33, 35-40, 47-48, 50, 54 and 56 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9, 12-19, 22-29 of U.S. Patent No. 11524023. Although the claims at issue are not identical, they are not patentably distinct from each other because although claims of ‘023 are to a composition, applicant’s claims only require treatment of a composition with ionizable, tertiary amine containing lipid and polynucleotide/mRNA with treatments including a number of items as provided in applicant’s claim 54. Since ‘023 teaches such amounts of adduct impurity as well as the storage under controlled temperature and inclusion of a buffer like Tris, its claims obviate the method claims of applicant. In regards to lipoplexes and liposomes, these are seen as other acceptable forms of lipid particles.
Claims 30-40, 47-48, 50, 54 and 56 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of U.S. Patent No. 11622972. Although the claims at issue are not identical, they are not patentably distinct from each other because although claims of ‘972 are to a composition, applicant’s claims only require treatment of a composition with ionizable, tertiary amine containing lipid and polynucleotide/mRNA with treatments including a number of items as provided in applicant’s claim 54. Since ‘972 teaches such amounts of adduct impurity as well as the storage under controlled temperature and inclusion of a buffer like Tris, its claims obviate the method claims of applicant. In regards to lipoplexes and liposomes, these are seen as other acceptable forms of lipid particles.
Claims 30-40, 47-48, 50, 54 and 56 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 12508278. Although the claims at issue are not identical, they are not patentably distinct from each other because although claims of ‘278 are to a method of administering to a subject, applicant’s claims only require treatment of a composition with ionizable, tertiary amine containing lipid and polynucleotide/mRNA with treatments including a number of items as provided in applicant’s claim 54. Since ‘278 teaches such amounts of adduct impurity as well as the storage under controlled temperature and inclusion of a buffer like Tris, its claims obviate the method claims of applicant. In regards to lipoplexes and liposomes, these are seen as other acceptable forms of lipid particles.
Claims 30-33, 35-44, 50, and 54-56 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7, 10-15, 17-19, 24-25 of U.S. Patent No. 11583504. Although the claims at issue are not identical, they are not patentably distinct from each other because although claims of ‘504 are to a formulation, applicant’s claims only require treatment of a composition with ionizable, tertiary amine containing lipid and polynucleotide/mRNA with treatments including a number of items as provided in applicant’s claim 54. Since ‘504 teaches the storage under controlled temperature and inclusion of a buffer like Tris, its claims obviate the method claims of applicant. ‘504 also provides for, pH such as 7.4, addition of chelators or antioxidants (reducing agents). ‘504 is silent to amounts of adduct impurities, but as it provides for formulations that would include treatments of applicant’s claims along with the components of the composition of applicant’s claims, it is capable of having such adduct impurity amounts. In regards to lipoplexes and liposomes, these are seen as other acceptable forms of lipid particles.
Claims 30-33, 35-44, 50, and 54-56 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 8, 18-21 of U.S. Patent No. 12144895. Although the claims at issue are not identical, they are not patentably distinct from each other because although claims of ‘895 are to a lipid nanoparticle formulation, applicant’s claims only require treatment of a composition with ionizable, tertiary amine containing lipid and polynucleotide/mRNA with treatments including a number of items as provided in applicant’s claim 54. Since ‘895 teaches the storage under controlled temperature via cryoprotectant, its claims obviate the method claims of applicant. ‘895 also provides for, pH such as 7.4, addition of chelators or antioxidants (reducing agents). ‘895 is silent to amounts of adduct impurities, but as it provides for formulations that would include treatments of applicant’s claims along with the components of the composition of applicant’s claims, it is capable of having such adduct impurity amounts. In regards to lipoplexes and liposomes, these are seen as other acceptable forms of lipid particles.
Claims 30-33, 35-48, 50 and 54-56 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-34 of copending Application No. 19/384,380 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because ‘380 provides for compositions and a process that address amounts of adduct impurities as well as treatments/treated forms that formulations with ionizable lipid and mRNA as in the applicant’s claims. In regards to lipoplexes and liposomes, these are seen as other acceptable forms of lipid particles.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Advisory Notice
Claim 46 is free of the prior art. However, note that it is currently rejected under USC 112(b) as being dependent on claim 45 (indefinite) and indirectly dependent on claim 50 (indefinite). If the applicant corrects the claims to overcome the 112(b) rejections along with any other issues (objections, double patenting, etc) and imports the limitation of claim 46 into claim 50. The applicant will have an independent claim that is free of the prior art (potentially allowable if no other issues are introduced in the amendment). Note that adding the limitation of claim 46 into claim 50 may necessitate changes to any dependent claims after such an incorporation.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARK V STEVENS whose telephone number is (571)270-7080. The examiner can normally be reached M-F 9:00 am to 6:00 pm EST.
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/MARK V STEVENS/Primary Examiner, Art Unit 1613