DETAILED ACTION
Applicants’ arguments, filed 8 June 2026, have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Withdrawn Rejection Due to AIA Exception
Previously in prosecution, the examiner rejected the instant claims as being obvious over Smith et al. (WO 2021/155274 A1). This rejection has been withdrawn by the examiner because the above-cited reference is not prior art in view of the AIA 35 U.S.C. 102(b)(2)(C) exception. The examiner presents the following reasoning in support of this position.
In applicant’s response on 8 June 2026 (hereafter referred to as applicant’s response), applicant takes the following position:
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Exceptions under AIA 35 U.S.C. 102(b)(2)(C) are discussed in MPEP 2154.02(c). The last paragraph of MPEP 2154.02(c) emphasizes that a clear and conspicuous statement on the record is sufficient to establish the AIA 35 U.S.C. 102(b)(2)(C) exception. This paragraph of the MPEP also states that the Office will not request corroborating evidence in the absence of independent evidence which raises doubt as to the veracity of such a statement. In this case, there does not appear to be independent evidence raising a doubt to the veracity of common assignment. As such, the above-reproduced statement from applicant’s response is understood to be sufficient to invoke the exception under AIA 35 U.S.C. 102(b)(2)(C) and is sufficient to overcome the previously applied rejection over Smith et al. (WO 2021/155274 A1).
Note Regarding Claim Amendment Support
Applicant amended claim 1 to recite the following.
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In applicant’s response on 8 June 2026 (hereafter referred to as applicant’s response), applicant cites figure 5 as providing support for the above-indicated claim limitation. The examiner has reproduced figure 5 below.
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The examiner takes the position that, although there is no in haec verba support for the phrase “that is diluted relative to the intermediate step.” Nevertheless, it appears from the above-reproduced figure that the composition at the stage of “empty-LNP solution” is diluted relative to the composition at the stage of “holding step.” As such, this figure appears to adequately support the amendment to claim 1. The subject matter of the claim need not be described literally (i.e., using the same terms or in haec verba) in order for the disclosure to satisfy the description requirement. See MPEP 2163.02, last paragraph.
Claim Rejections - 35 USC § 103 – Obviousness
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.
Claim(s) 1, 5, 9, 15, 17, 19, 23, 27, 29, 32, 35-37, 114-116, 131-137, and 140 is/are rejected under 35 U.S.C. 103 as being unpatentable over Karve et al. (US 2018/0153822 A1).
Karve et al. (hereafter referred to as Karve) is drawn to a method of preparing mRNA loaded lipid nanoparticles by combining mRNA with pre-formed lipid nanoparticles, as of Karve, title, abstract, and figure 2, reproduced below.
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As to step (i-a), Karve teaches mixing lipids in a solvent which is ethanol with an aqueous citrate buffer to form empty lipid nanoparticles, as of paragraph 0167. Karve teaches that the lipids may be a cationic lipid, a helper lipid, a PEG-lipid, and a cholesterol lipid, as of Karve, paragraph 0013. Karve teaches various phospholipids as the helper lipid as of paragraph 0016. The cationic lipid may be one selected from the group taught as of paragraph 0014 of Karve, which are all ionizable cationic lipid. The cholesterol lipid of Karve reads on the required structural lipid, and Karve teaches various PEG lipids in paragraphs 0158-0159.
As to step (i-b), the skilled artisan would have expected that the empty particles of Karve, which Karve refers to as “pre-formed” particles or pre-formed LNPs (wherein the term “LNP” refers to “lipid nanoparticle”) would have been held for a time period before loading.
As to step i-c of claim 1, the skilled artisan would have been motivated to have broken the step of adding aqueous solution into a first step which reads on step i-a and a second step which reads on step i-c. This modification would have been an example of changing the sequence of adding ingredients, in which a first part of the aqueous phase was added first and a second part of the aqueous phase added second as opposed to all of the aqueous phase having been added at once. Selection of any order of mixing ingredients is prima facie obvious; see MPEP 2144.04(IV)(C). Additionally, the examiner notes that making a non-continuous process continuous is understood to be prima facie obvious; see MPEP 2144.04(IV)(E). In a similar vein, the skilled artisan would have understood that making a process that is continuous in the prior art to be discontinuous would also have been prima facie obvious. As such, a prior art method in which all of the aqueous phase is added at once is sufficient to render the claimed method, in which part of the aqueous phase is added in step i-a and the other part of the aqueous phase added in step i-c prima facie obvious.
As to step (ii) of claim 1, Karve teaches loading the empty lipid nanoparticles with nucleic acid, which may be mRNA, as of at least figure 2 of Karve. Also see Karve, paragraph 0020, as well as other portions of the Karve reference.
As to claim 1, Karve appears to teach all of the claimed requirements, but not in the same part of the reference. As such, while the prior art teaches all of the claimed components, the prior art is not anticipatory insofar as these components must be selected from various lists/locations in the prior art reference. It would have been prima facie obvious; however, to have selected the recited components from various lists/locations in the prior art reference and to have combined them together. This is because such a modification would have represented nothing more than the predictable use of prior art components according to their established functions. Combining separate prior art components (from a single prior art reference) according to known methods to yield predictable results is prima facie obvious. See MPEP 2143, Exemplary Rationale A.
As to claim 5, the filtration process of Karve, e.g. paragraphs 0186-0187, can be understood to read on a required processing step.
As to claim 9, Karve teaches a phosphate buffer in paragraph 0119.
As to claim 15, the skilled artisan would have expected that the steps of filtration, as of Karve, paragraphs 0186-0187, followed by diluting, as of Karve, paragraph 0188, would have taken more than 1 minute and less than 1 hour, as this is a reasonable amount of time that it takes to conducted a laboratory procedure. This would have resulted in a residence time in the claimed range.
As to claim 17, Karve teaches the use of pH 4.5 buffer, as of Karve, page 37, claim 31.
As to claim 19, the apparent diluting step described by paragraph 0188 of Karve would appear to entail mixing the nanoparticles of Karve with a buffer that is free of PEG-lipid.
As to claim 23, Karve teaches filtering, as of Karve, at least paragraphs 0186-0187.
As to claim 27, Karve teaches trehalose and sucrose in paragraph 0027; the skilled artisan would have understood these to have been known cryoprotectants even if Karve does not teach sucrose and trehalose for this purpose.
As to claim 29, Karve teaches a pH of 3.5-6.5 as well as narrower ranges therein, as of Karve, paragraph 0121. This would appear to overlap with the claimed range. While the prior art does not disclose the exact claimed values, but does overlap: in such instances even a slight overlap in range establishes a prima facie case of obviousness. See MPEP 2144.05(I).
As to claim 32, the method of adding phosphate buffered saline in paragraph 0188 of Karve would appear to read on the required pre-loading buffer addition step.
As to claim 35, Karve teaches mRNA as of at least paragraph 0122.
As to claim 36, Karve teaches a pH of 3.5-6.5 as well as narrower ranges therein, as of Karve, paragraph 0121. This would appear to overlap with the claimed range. While the prior art does not disclose the exact claimed values, but does overlap: in such instances even a slight overlap in range establishes a prima facie case of obviousness. See MPEP 2144.05(I).
As to claim 37, the skilled artisan would have expected that more than 5 seconds would have elapsed between preparing of the raw particles and the filtration described by Karve, paragraphs 0186-0187.
As to claim 114, Karve teaches cholesterol as of at least paragraph 0161.
As to claim 115, Karve teaches DSPC as of at least paragraph 0033.
As to claim 116, Karve teaches DMG-PEG2K in paragraph 0161, which is understood to read on the claimed requirements.
As to claim 131, while Karve teaches sucrose and trehalose in paragraph 0027, these appear to be optional ingredients. As such, the skilled artisan would have been motivated to have conducted a method in which sucrose and trehalose were not used. Additionally, the method of Karve does not appear to recite a lyophilization step; therefore, the skilled artisan would not have necessarily used sucrose and trehalose for this purpose.
As to claim 132, Karve teaches a pH of 3.5-6.5 as well as narrower ranges therein, as of Karve, paragraph 0121. This would appear to overlap with the claimed range. While the prior art does not disclose the exact claimed values, but does overlap: in such instances even a slight overlap in range establishes a prima facie case of obviousness. See MPEP 2144.05(I).
As to claim 133, Karve teaches maintaining at ambient temperature, which may be less than 25°C, 20°C, or 16°C, as of Karve, paragraph 0011.
As to claim 134, Karve teaches ethanol, as of Karve, paragraph 0042.
As to claim 135, Karve teaches a pH of 3.5-6.5 as well as narrower ranges therein, as of Karve, paragraph 0121. This would appear to overlap with the claimed range. While the prior art does not disclose the exact claimed values, but does overlap: in such instances even a slight overlap in range establishes a prima facie case of obviousness. See MPEP 2144.05(I).
As to claim 136, Karve teaches mRNA as of at least paragraph 0122.
As to claim 137, Karve teaches a pH of 3.5-6.5 as well as narrower ranges therein, as of Karve, paragraph 0121. This would appear to overlap with the claimed range. While the prior art does not disclose the exact claimed values, but does overlap: in such instances even a slight overlap in range establishes a prima facie case of obviousness. See MPEP 2144.05(I).
As to claim 140, Karve teaches cholesterol as of at least paragraph 0161, DSPC as of at least paragraph 0033, and DMG-PEG2K in paragraph 0161, which is understood to read on the claimed requirements.
Claim(s) 3, 20, and 40 is/are rejected under 35 U.S.C. 103 as being unpatentable over Karve et al. (US 2018/0153822 A1) in view of Candiani (“Non-Viral Gene Delivery Vectors” Methods in Molecular Biology 1445, Springer Protocols, Humana Press, 2016, pages i-xiii and 1-289).
Karve is drawn to a method for preparing lipid nanoparticles. See the rejection above over Karve by itself.
Karve does not teach storing empty lipid nanoparticles in the form of a solution for about 1 hour to about 5 years.
Candiani is drawn to delivery of genetic material such as DNA and RNA without viral vectors, as of Candiani, title, abstract, and preface on page v. Candiani teaches nanocarriers for delivery of RNA, as of Candiani, Chapter 13, starting on page 201. Candiani teaches that empty lipid nanoparticles can be stored at 4°C (i.e. the temperature of a refrigerator) up to 120 days, as of Candiani, page 209, Note 8.
It would have been prima facie obvious for one of ordinary skill in the art to have stored the empty particles of Karve for the time period taught by Candiani. Karve teaches preparing pre-formed empty lipid nanoparticles, followed by a later step of adding the nucleic acid. Candiani teaches that empty lipid nanoparticles can be stored for up to 120 days at refrigerator temperature. As such, the skilled artisan would have been motivated to have stored the particles of Karve for the time period taught by Candiani in order to have predictably preserved the particles of Karve prior to use with a reasonable expectation of success. The skilled artisan would have been motivated to have optimized the storage time in the case wherein the particle would have needed to have been transported from one place to another prior to use or where the particles would have needed to have been stored prior to use.
As to claim 3, the amount of time of up to 120 days overlaps with the requirement of 1 hour to about 5 years. While the prior art does not disclose the exact claimed values, but does overlap: in such instances even a slight overlap in range establishes a prima facie case of obviousness. See MPEP 2144.05(I).
As to claim 20, Candiani teaches a method in which PEG-lipid was added in the diluting step as opposed to the step of making the particle, as of Candiani, page 206, figure 1, reproduced below.
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The examiner notes that this method differs from the claimed method because the method in the above-reproduced figure uses cationic polymer rather than cationic lipid. Nevertheless, it still provides motivation for the skilled artisan to have added PEG-lipid in a later dilution step rather than in the step of making the particle.
As to claim 40, this claim is rejected for essentially the same reason that claim 20 is rejected.
Claim(s) 8, 18, 112 and 138-139 is/are rejected under 35 U.S.C. 103 as being unpatentable over Karve et al. (US 2018/0153822 A1) in view of Benenato et al. (US 2017/0210698 A1).
Karve is drawn to a method for preparing lipid nanoparticles. See the rejection above over Karve by itself.
Karve does not teach the ionizable lipid required by claim 112.
Benenato et al. (hereafter referred to as Benenato) is drawn to lipid nanoparticles for delivering RNA, as of Benanto, title and abstract. The particles of Benenato comprise ionizable cationic lipids, as of Benenato, paragraph 0005. The lipid of Benenato may have the following structure, as of Benenato, page 15, relevant compound reproduced below.
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It would have been prima facie obvious for one of ordinary skill in the art to have substituted the ionizable cationic lipid of Benenato in place of the ionizable cationic lipid of Karve to be used in the nanoparticles of Karve and the method of making the nanoparticles of Karve. Both Benenato and Karve are drawn to lipid nanoparticles comprising an ionizable cationic lipid for delivery of nucleic acid, though the chemical structures of the ionizable cationic lipids in Karve and Benenato differ from each other. Nevertheless, the skilled artisan would have been motivated to have substituted the ionizable cationic lipid of Benenato in place of that of Karve in order to have predictably delivered a nucleic acid with a reasonable expectation of success. The simple substitution of one known element (e.g. the ionizable cationic lipid of Benenato) in place of another (e.g. the ionizable cationic lipid of Karve) in order to achieve predictable results (delivery of a nucleic acid) is prima facie obvious. See MPEP 2143, Exemplary Rationale B.
As to claim 8, Benenato teaches tromethamine as a buffer in paragraph 0435. The skilled artisan would have expected that tromethamine, which is also known as “Tris”, would have had a pKa of about 8.1. This would have motivated the skilled artisan to have utilized a buffer with a pH that is equal to the pKa of tromethamine, and which is in the range required by this claim. See the section above entitled “Note Regarding Tris (i.e. Tromethamine) Buffer.”
As to claim 18, Benenato teaches an acetate buffer in paragraph 0435.
As to claim 112, the lipid of Benenato reads on the additional requirement of this claim.
As to claim 138, Benenato teaches an acetate buffer in paragraph 0435.
As to claim 139, this claim is rejected for essentially the same reason that claim 8 is rejected.
Response to Arguments Regarding Obviousness Rejection
Applicant has presented arguments regarding the previously applied obviousness rejection, as of applicant’s response on 8 June 2026 (hereafter referred to as applicant’s response). These arguments are addressed below.
In the previously applied rejection, the examiner took the position that the diafiltration step taught by Karve can read on the required step i-c. Applicant has disputed this position as of applicant’s response, paragraphs bridging pages 8-9, relevant text reproduced below.
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The examiner does not dispute the position taken in the above-reproduced text. As such, in view of applicant’s response, the examiner no longer takes the position that the diafiltration step in Karve is sufficient to read on claimed step (i-c).
With that being said, the examiner’s agreement with applicant on this issue is not sufficient to overcome the previously applied rejection. This is because, in the previously applied rejection, the examiner noted two alternative teachings from Karve intended to read on claimed step (i-c). The second alternative teaching was discussed in the paragraph bridging pages 6-7 of the prior office action and is also discussed above. Applicant provided arguments regarding this paragraph on the last two paragraphs of page 9 of applicant’s response. Select arguments from these paragraphs are reproduced below.
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Applicant also makes the following argument.
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In view of this argument, the examiner has decided to review MPEP 2143(I)(A), Example 3, citing In re Omeprazole Patent Litigation, 536 F.3d 1361, 87 USPQ2d 1865 (Fed. Cir. 2008). This is because the examiner takes the position that there are sufficient similarities between the above-cited case and the fact pattern of the instant application that the MPEP guidance regarding the above-cited example is sufficient to support the examiner’s decision to maintain the applied rejection. The examiner has explained this in greater detail below.
The examiner clarifies that, consistent with USPTO policy, the above-discussed analysis is based solely upon the MPEP summary of the cited case, and not on the text of the cited case itself.
MPEP 2143(I)(A), Example 3, states the following in the three paragraphs and the beginning of the fourth paragraph of the example:
The case of In re Omeprazole Patent Litigation, 536 F.3d 1361, 87 USPQ2d 1865 (Fed. Cir. 2008), is one in which the claims in question were found to be nonobvious in the context of an argument to combine prior art elements. The invention involved applying enteric coatings to a drug in pill form for the purpose of ensuring that the drug did not disintegrate before reaching its intended site of action. The drug at issue was omeprazole, the generic name for gastric acid inhibitor marketed as Prilosec®. The claimed formulation included two layers of coatings over the active ingredient.
The district court found that Astra’s patent in suit was infringed by defendants Apotex and Impax. The district court rejected Apotex’s defense that the patents were invalid for obviousness. Apotex had argued that the claimed invention was obvious because coated omeprazole tablets were known from a prior art reference, and because secondary subcoatings in pharmaceutical preparations generally were also known. There was no evidence of unpredictability associated with applying two different enteric coatings to omeprazole. However, Astra’s reason for applying an intervening subcoating between the prior art coating and omeprazole had been that the prior art coating was actually interacting with omeprazole, thereby contributing to undesirable degradation of the active ingredient. This degradation of omeprazole by interaction with the prior art coating had not been recognized in the prior art. Therefore, the district court reasoned that based on the evidence available, a person of ordinary skill in the art would have had no reason to include a subcoating in an omeprazole pill formulation.
The Federal Circuit affirmed the district court’s decision that the claimed invention was not obvious. Even though subcoatings for enteric drug formulation were known, and there was no evidence of undue technical hurdles or lack of a reasonable expectation of success, the formulation was nevertheless not obvious because the flaws in the prior art formulation that had prompted the modification had not been recognized. Thus there would have been no reason to modify the initial formulation, even though the modification could have been done. Moreover, a person of ordinary skill in the art likely would have chosen a different modification even if they had recognized the problem.
Office personnel should note that in this case the modification of the prior art that had been presented as an argument for obviousness was an extra process step that added an additional component to a known, successfully marketed formulation. The proposed modification thus amounted to extra work and greater expense for no apparent reason. …
The examiner takes the position that the fact pattern described above appears to have significant similarities to the fact pattern of the claimed invention. This is because in both the above-cited case and the claimed invention, the claims appear to introduce a difference that, as compared with the prior art, makes the claimed invention appear to amount to extra work and greater expense for no apparent reason. In the exemplified method of Karve, the method entails adding the entirety of the aqueous solution to the lipid solution in ethanol, followed by later addition of nucleic acid. In contrast, in the claimed method, it appears that the lipid solution in ethanol is mixed with aqueous solution in a piecemeal manner, with some of the aqueous solution being added in step (i-a) and other of the aqueous solution being added in step (i-c). This would appear to render the claimed method to be more complicated than the method of Karve, thereby amounting to extra work and greater expense for no apparent reason. This is similar to the cited case wherein addition of the subcoating in the cited case amounted to extra work and greater expense for no apparent reason.
The above-reproduced text also states that in the cited case, there was no evidence of unpredictability, no evidence of technical hurdles, and no evidence of a lack of a reasonable expectation of success in making the modification of adding the subcoating. Likewise, in the instant case, there would not have been unpredictability or technical hurdles in adding the aqueous solution in two separate steps rather than a single step, as in Karve. There would also have been no evidence to suggest that modifying Karve to have added the aqueous solution in two separate steps would have lack a reasonable expectation of success.
As such, these appear to amount to significant similarities between the fact pattern of the instant case and that of the cited case. With that being said, the fact pattern of the instant application appears to diverge from that of the cited case for the following reasons.
First, the applicant in the cited case appears to have discovered a previously unrecognized problem in the prior art that was solved by addition of the subcoating. A feature like this does not appear to be the case in the fact pattern of the instant application. This is because nothing in the instant application indicates that there is a problem in Karve caused by adding the entirety of the aqueous phase at once that was solved by adding the aqueous phase in two separate steps. Additionally, nothing in applicant’s response points to unexpectedly improved results in the claimed method as compared with the method of Karve.
Secondly, it remains the examiner’s position that the differences between Karve and the claimed invention can be whittled down to a difference in the steps of adding ingredients or the steps of mixing ingredients. This is because in the method of Karve, the aqueous solution was added to the lipid/ethanol solution all at once, whereas in the claimed method, the aqueous solution was added to the lipid/ethanol solution in two separate stages. The examiner understands this to be a difference in the order of mixing ingredients. Selection of any order of performing process steps is prima facie obvious in the absence of new or unexpected results, and selection of any order of mixing ingredients is prima facie obvious. See MPEP 2144.04(IV)(C). This would appear to support the idea that the instantly claimed method is prima facie obvious over that of Karve even if the instantly claimed method appears to be more complicated than that of Karve for no apparent reason.
As such, the factors in the cited case that were sufficient to overcome the applied prior art do not appear to be present in the fact pattern of the instant case. As such, the previously applied rejection has been maintained.
Non-Statutory 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, 5, 9, 15, 17-20, 23, 27, 29, 32, 35-37, 40, 112, 114-116 131-138 and 140 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 148-152, 154, 156-161, 163-172, and 174-176 of copending Application No. 17/792,554 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because of the following reasons:
The instant claims are drawn to a method of preparing lipid nanoparticles. The method of claim 1 entails mixing lipid solution in alcohol with aqueous solution to form empty lipid nanoparticles. These are held for a residence time then diluted. Following dilution, a loading step occurs in which a nucleic acid is loaded. Instant claim 3 recites storing for about 1 hour to about 5 years.
Copending claim 148 is drawn to a method of preparing a loaded lipid nanoparticle. The first step involves mixing a lipid solution with an aqueous acetate buffer to form an empty lipid nanoparticle solution. Following this, a loading step occurs in which nucleic acid is loaded.
Instant claim 1 and copending claim 148 differ because instant claim 1 recites a holding and a diluting step, which is not recited by copending claim 1. Nevertheless, copending claim 150 recites a pH adjusting step which entails adding a second buffering agent, as of copending claims 150-151. The skilled artisan would have understood that this would have read on the diluting step of part i-c of claim 1. As such, the skilled artisan would have been motivated to have held the intermediate solution prior to the pH change before adding the solution to change the pH. Also, the skilled artisan would have been motivated to have used ethanol as the organic solvent to dissolve the lipid components, as of copending claim 159. As such, this results in a prima facie case of obviousness-type non-statutory double patenting.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
This rejection does not apply to instant claims 8 and 139. This is because these claims recite an aqueous buffer with a pH of 8.0 to 9.5 or 10.0. This is not recited by the claims of the ‘554 application. In fact, claims 156-157 appear to recite using aqueous buffers with a maximum pH of about 5.75. This results in significant differences between the claims of the ‘554 application and the instantly claimed invention. This is because the pH values recited by the ‘554 application are most likely lower than the pKa of the ionizable cationic lipid incorporated into a lipid nanoparticle. In contrast, the recited pH values of 8.0 to 10.0 are most likely higher than the pKa of the ionizable lipid when incorporated in a lipid nanoparticle (though these pH values may be lower than or equal to the pKa of the ionizable lipid when not part of the lipid nanoparticle). Regardless, the claimed method would have been expected to have prepared a deprotonated empty lipid nanoparticle, whereas the method of the claims of the ‘554 application would have expected to have formed a protonated empty lipid nanoparticle. These nanoparticles would have had significantly different structures, as illustrated by Kulkarni et al. (Nanoscale, Vol. 11, 2019, pages 9023-9031), specifically as of page 9025, right column, top paragraph, which teaches small bilayer structures at pH 4 but larger electron dense structures at pH 7.4.
Response to Arguments Regarding Double Patenting Rejection
In applicant’s response on 8 June 2026, applicant has deferred addressing the double patenting rejection until the application is otherwise in condition for allowance, as of applicant’s response, page 11. As such, the double patenting rejection has been maintained.
Conclusion
No claim is allowed.
THIS ACTION IS MADE FINAL. 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 ISAAC SHOMER whose telephone number is (571)270-7671. The examiner can normally be reached 7:30 AM to 5:00 PM Monday Through Friday.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sahana Kaup can be reached at (571)272-6897. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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ISAAC . SHOMER
Primary Examiner
Art Unit 1612
/ISAAC SHOMER/ Primary Examiner, Art Unit 1612
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