DETAILED ACTION
Claims 1-15 are currently pending and under examination.
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 .
Withdrawn Rejections
The prior objection of claims 4-15 are being improper form is withdrawn as a result of the claim amendments submitted 02/03/2025, prior to the previous office action dated 03/12/2026, thus the objection is withdrawn.
Examiner’s Note
Applicant's amendments and arguments filed 06/12/2026 are acknowledged and have been fully considered. The Examiner has re-weighed all the evidence of record. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.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.
Modified and New Rejections:
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 2-3 and 14 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.
Claim 2 recites the limitation "the mixing flow rate" in the second line. There is insufficient antecedent basis for this limitation in the claim. Instant claim 1, from which it depends contains a mixing of the first and second components, however does not recite a “mixing flow rate”. Claim 3 is further rejected as not remedying the ambiguity of claim 2.
Claim 14 contains the limitation of wherein said aqueous solution… is water. It is unclear how the aqueous solution is water, excluding additional ingredient but has a pH of less than 6.5, wherein acidic water would require additional ingredients than just water, leading to unclear metes and bounds. For examination purposes, the aqueous solution will be deemed to require water but not exclude additional ingredients.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1, 4-9 are 11-15 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2021/0284974 (previously applied) in view of US 2021/0187049 (previously applied).
Regarding claims 1 and 14, the limitation a method for the large-scale production of a composition comprising lipid nanoparticle having an average diameter of at least 140 nm, said method comprising the steps of mixing a first composition containing an ionizable lipid, a phospholipid, a sterol and a PEG lipid in an organic solvent with a second composition comprising one or more active agents in an acidic buffer, thereby obtaining a post mixing bulk is met by the ‘974 publication teaching compositions include a lipid formulation and a mRNA (abstract). Lipid nanoparticles contain the size from 10 nm to 1000 nm ([0184], [0192]). As MPEP 2144.05 recites “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine optimization”. The lipid nanoparticle is taught to include mRNA, cationic lipid, PEG lipid, neutral lipid and a sterol ([0199]-[0205]). Lipid encapsulated mRNA particles were prepared by mixing lipids (ionizable cationic lipid: DSPC: Cholesterol: PEG-DMG) in ethanol with mRNA dissolved in citrate buffer [0475]. Large scale production is taught as desired [0183].
The limitation of applying tangential flow filtration to said post mixing bulk, applying a filtration step in an aqueous solution having a pH less than 6.5 to said composition, adding a cryobuffer comprising a cryoprotectant, applying a filtration step in an aqueous solution having a pH greater than 6.5 to said composition of step d is met by the ‘974 publication teaching the mixed material diluted with phosphate buffer, ethanol removed by tangential flow filtration. Once the ethanol is removed, the buffer was exchanged with HEPES buffer (pH 7.3) and cryoprotectant. The formation was filtered to a final desired concentration by diluting with HEPES buffer and sucrose containing glycerol. The final formulation is then filtered and filled into glass vials [0475].
Regarding the limitation of sterile filtration of said composition is met by the ‘974 publication teaching final formulation was then filtered through a 0.2 um filter and filled into glass vials [0475] wherein the instant specification evidences sterile filtration is typically filtering through a 0.2 micrometer pore size (page 9, line 34-page 10, line5).
Regarding the claim limitation of LNPs comprising less than 1 mol% of PEGylated lipid is met by the ‘974 publication teaching about 0.5 mol% to 3 mol% of PEG2000-DMG [068].
Regarding claim 6, the limitation of wherein the organic solvent is an alcohol is met by the ‘974 publication teaching ethanol [0475].
Regarding claim 7, the limitation of wherein said active agent is selected from small molecules or biomolecules, wherein the biomolecules are selected form nuculid acids, antibodies, proteins, or peptides is met by the ‘974 publication teaching mRNA [0475] and nucleic acids as therapeutic agents [0012].
Regarding claim 8-9, the limitation of wherein the cryobuffer is selected from maltose, maltodextrin, dextran, mannitol trehalose glucose or sucrose and further comprise citrate, tris and pbs is met by the ‘974 publication teaches buffers and cryoprotectant including sucrose [0070], wherein buffers are taught to include HEPES, TRIS [0293].
Regarding claim 11, the limitation of wherein the post mixing bulk obtained step a) is diluted before step b) is met by the ‘974 publication teaching the mixed material is diluted with phosphate buffer [0475].
Regarding claim 12, the limitation of wherein the composition obtained in step e is diluted before step f is met by the ‘974 publication teaching diluting after filtration before the final formation was filed [0475].
Regarding claim 13 and 15, the 974 publication teaches 0.2 um filtration using PES filters [0475].
The ‘974 publication does not specifically teach TFF of step b) is performed at a shear rate of less than 4000/s (claim 1), wherein the tangential flow filtration in step b) comprises a plurality of tangential flow filtration steps, wherein the first ultrafiltration step is performed at a lower shear rate compared to other tangential flow filtration step (claim 4).
The ‘049 publication teaches purified compositions of enterovirus, pharmaceutical compositions thereof (abstract). A scalable robust enterovirus purification process involving enterovirus purification process includes the use of buffer exchange step using tangential flow filtration and a final filtration step [0018]. The purification is buffer exchanged via tangential flow filtration. TFF may be operated with a crossflow shear rate of about 1,000-8,000/s. The buffering is taught at 6-8, with an optional neutralization step, an optional filtrations step and buffer exchange. Tff of 2000/s is taught [0110], thus teaching multiple filtration steps and an optimizable shear rate. As MPEP 2144.05 recites “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine optimization”.
It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to use known flow rates for tff as taught by the ‘049 publication for the tff process taught by the ‘974 publication because the ‘974 publication and the ‘049 publication are directed to particle purification steps comprising tff and buffer exchange and the ‘974 publication is directed to particle purification using tff and buffer exchange. It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to use know flow rates for tff used in purification of particles as taught by the ‘049 publication for lipid particle purification as taught by the ‘974 publication. It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to use multiple tangential flow filtration steps at differing shear rates as the ‘049 publication teaches the use of multiple filtration steps and a range of shear rat for TFF and the ‘974 publication teaches the use of tff in the method of encapsulation.
Claim(s) 2-3 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2021/0284974 in view of US 2021/0187049 as applied to claims 1, 4-9 are 11-15 above, and further in view of US 2013/0037977 (previously applied).
As mentioned in the above 103 rejection, all of the limitations of claim 1, 4-9 are 11-15 is taught by the combination of the ‘974 publication and the ‘049 publication.
The combination of references does not specifically teach the mixing flow rate of the first comprising is lower than the mixing flow rate of the second composition (claim 2) wherein the ratio between the first and the second composition is about 1:2 (claim 3).
The ‘977 publication teaching preparation of lipid nanoparticles by encapsulating therapeutic products. The process comprising providing one or more aqueous solutions in one or more reservoirs and one or more organic solutions in one or more reservoirs, mixing said one or more aqueous solution and one or more organic solutions in a first mixing region (abstract). The mixing is taught to be qual flow rates. Lipid nanoparticles are substantially instantaneously formed. Lipid nanoparticles are formed when an organic solution including dissolved lipid and an aqueous solution (buffer) are instantaneously and continuously mixed. The pump mechanisms can be configured to provide equivalent or different flow rates of the lipid and aqueous solution into the mixing environment [0068]. One or more streams is taught to at high volume flow rate and one other stream at a lower flow rate and still achieve good micromixing, that ratio of organic to buffer solutions can be manipulated to effect better control over lipid particle properties such as particle size and stability [0069].
Thus it would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to use known mixing flow rates and optimize for the particle formation taught by the ‘974 publication because he ‘977 publication teaches known mixing rates and motivation to optimize the mixing rate of the organic and aqueous solution, to obtain the desired particle size and stability. As MPEP 2144.05 recites “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine optimization”.
Claim(s) 10 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2021/0284974 in view of US 2021/0187049 as applied to claims 1, 4-9 are 11-15 above, and further in view of US 2021/0353556.
As mentioned in the above 103 rejection, all of the limitations of claim 1, 4-9 are 11-15 is taught by the combination of the ‘974 publication and the ‘049 publication.
The ‘556 publication does not specifically teach wherein the first composition of step a) is at a temperature of 30-45 degree C (claim 10).
The ‘556 publication teaches encapsulating messenger RNA in lipid nanoparticles without the use of flammable solvents (abstract). The ambient temperature is taught to be less than 35 degrees C [0012]-[0013] wherein the mRNA solution and/or the lipid solution are at about ambient temperatures [0011]. The process is taught to include tangential flow filtration and one or more cholesterol based lipids ([0027]-[0028]). The use of a mixed flow rate is taught ([0034]-[0038]). The mRNA solution is taught by missing mRNA stock solution with buffer immediately before mixing with a lipid solution for encapsulation. Suitable mRNA solution includes buffering agent such as HEPES, sodium citrate [0100]-]0139]).
It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to use the ambient mixing temperature as taught by the ‘556 publication for the encapsulation taught by the ‘974 publication because the ‘974 publication teaching lipid and mRNA solutions to be mixed and the ’556 publication teaches ambient temperatures for mRNA and lipid solution to include less than 35 degrees C, thus teaching a known range for mRNA lipid encapsulation wherein the ‘974 publication teaches mRNA lipid encapsulation methods. It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to use known temperatures for mRNA and lipids in lipid encapsulation method for the lipid encapsulation taught by the ‘974 publication as the ‘974 publication is silent to the temperature and the ‘556 publication teaches known temperatures.
Response to Arguments:
Applicant argues the claims examined are the original claims dated 06/12/2024, wherein the most recent claims are dated 02/03/2026.
In response, the instant action is non-final based on examination of the incorrect claim set. The instant action is based on claims submitted 06/12/2026.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LYNDSEY MARIE BECKHARDT whose telephone number is (571)270-7676. The examiner can normally be reached Monday-Thursday 9am to 4pm and Friday 9am to 2pm.
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/LYNDSEY M BECKHARDT/Examiner, Art Unit 1613
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