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 .
Priority
The application was filed 06 September 2022 and the Applicant claims priority to provisional application 63/241,317 filed 07 September 2021. Therefore, the effective filing date of the application is 07 September 2021.
Examiner’s Note
The Applicant's amendments and arguments filed 12 February 2026 are acknowledged and have been fully considered. The Examiner has re-weighed all the evidence of record. Rejections not reiterated from previous office actions are hereby withdrawn. The following rejections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application. In the Applicant’s response, filed 12 February 2026, it is noted that claims 1, 6, and 101 have been amended, claims 2-5, 7-9, 11-26, 28-49, 51-54, 56-100, 102, and 104-107 are canceled, and no claims have been newly added. The amendments have been made for clarity purposes. No new matter has been added.
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 (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 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.
Claim(s) 1, 6, 10, 27, 50, 55, 101, 103, 108, 109, 111, and 113, 114 is/are rejected under 35 U.S.C. 103 as being unpatentable over Benenato et al. (US 11,597,698 B2) and Schrader et al. (US 2023/0270842 A1), as evidenced by pubchem.
Benenato et al. teach lipid nanoparticle compositions that may include RNA (abs) or mRNA (col. 73, ln. 41), ionizable lipids (col. 1, lns. 40-43), and polymers (col. 82, lns. 8-12), addressing claims 1, 109, 111, and 114. The polymer may be used to encapsulate the nanoparticle composition (col. 82, lns. 13-15) and the therapeutic agent is encapsulated by the lipid nanoparticle (col. 91, lns. 16-21), addressing claim 1. The composition may include heptadecane-9-yl 8-((2-hydroxyethyl)(8-(nonyloxy)-8-oxooctyl)amino)octanoate (col. 115, lns. 11-12), which is lipid 5 (evidenced by pubchem, pg. 1), addressing claim 6. The polymers and copolymers may be PVP or PVA (col. 82, lns. 39-41), where it is interpreted that the copolymers may consist of both PVP and PVA together as repeating units, addressing the copolymer limitation in claim 1. Since Benenato teaches general copolymers, it is interpreted to include random and block copolymers. The nanoparticle composition may have a diameter between 50 and 300 nm (col. 66, lns. 63-67), which addresses the diameter of the nanoparticle in claim 10. In some embodiments, a cryoprotective agent, such as PEG of various lengths, may be included, such as DMG-PEG2000 (col. 86, ln. 40). The lipid component may be DOPE phospholipid or cholesterol (col. 86, lns. 39-41), addressing claim 113 since the composition may include lipid 5, DOPE, cholesterol, and DMG-PEG2000. The composition may be in a solid form (col. 94, ln. 52), addressing claim 108. The composition may comprise sucrose as an excipient (col. 63, lns. 29-54) in an amount of at least 50% (col. 92, lns. 1-9), addressing claim 27.
Benenato et al. do not teach a microneedle device, a w/w ratio of the copolymer to lipid nanoparticle, a mass ratio of 1:1: PVA:PVP, or a concentration of the biomolecule in claims 1, 50, 55, and 101.
Schrader et al. teach a microneedle device and composition (abs). One embodiment may include a lipid nanoparticle, such as an mRNA/RNA vaccine encapsulated by a lipid nanoparticle (para. 87, claim 36). In other embodiments, the lipid nanoparticle may comprise an ionizable lipid (para. 558), a polymeric material (para. 149) such as PVA or PVP (para. 167), and sucrose (para. 166). The nanoparticle may have a diameter of 200-1,000 nm (para. 556). The composition may comprise 5-15% sucrose (para. 175).
In regards to selecting the combination of copolymers, RNA, and lipid nanoparticle, “[w]hen a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious.” KSR v. Teleflex, 127 S.Ct. 1727, 1740 (2007) (quoting Sakraida v. A.G.Pro, 425 U.S. 273, 282 (1976)). “When the question is whether a patent claiming the combination of elements of prior art is obvious,” the relevant question is “whether the improvement is more than the predictable use of prior art elements according to their established functions.” (Id.). Addressing the issue of obviousness, the Supreme Court noted that the analysis under 35 USC 103 “need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” KSR at 1741. The Court emphasized that “[a] person of ordinary skill is… a person of ordinary creativity, not an automaton.” Id. at 1742.
Consistent with this reasoning, it would have been obvious to have selected various
combination of various disclosed ingredients from within a prior art disclosure, to arrive at compositions “yielding no more than one would expect from such an arrangement.”
Benenato teaches lipid nanoparticle compositions comprising RNA, ionizable lipids, and polymers, whereas the claimed invention is directed towards a composition comprising a polymer/copolymer and a lipid nanoparticle or biomolecule. Since Benenato teaches the individual components of the claimed composition, it is obvious for one of ordinary skill in the art to select the different combinations of ingredients to arrive at the claimed invention with a reasonable expectation of success.
Benenato teaches 0.1-100% of lipid nanoparticles (col. 92, lns. 25-27), 1-10% of an active ingredient (biomolecule) (col. 96, ln. 61-65), and sucrose as an excipient (col. 63, lns. 29-54) in an amount of at least 50% (col. 92, lns. 1-9). Schrader teaches polymers in an amount of 0.001-75% (para. 418) and 5-15% sucrose (para. 175). That being said and in lieu of objective evidence of unexpected results, the mass and w/w ratios of claim 1, w/w ratio in claim 101, mass ratio of PVA, PVP, and sucrose in claim 103, and concentration in claim 50 can be viewed as variables that achieves the recognized result of successfully making the lipid nanoparticle microneedle composition. The optimum or workable ranges of ratio and concentration can be accordingly characterized as routine optimization and experimentation (see MPEP 2144.05 (II)B). “[Discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art.” In re Boesch, 617 F.2d 272, 276 (CCPA 1980). Applicants provide no evidence of any secondary consideration such as unexpected results that would render the optimized amounts of ratios and concentrations as nonobvious.
Since Benenato et al. teach short needle devices (col. 96, lns. 43-56) but do not specify using a microneedle device, a mole ratio of the polymer to lipid nanoparticle, or a concentration of the biomolecule in claim 55, one of ordinary skill in the art would have been motivated to use the amount of polymers and microneedle teaching from Schrader et al. to address these deficiencies, as both Benenato and Schrader are directed towards lipid nanoparticle vaccine compositions comprising mRNA or RNA.
Claim(s) 1, 6, 10, 27, 50, 55, 101, 103, 108-114 is/are rejected under 35 U.S.C. 103 as being unpatentable over Benenato et al. (US 11,597,698 B2), Schrader et al. (US 2023/0270842 A1), and echelon-inc.com, as evidenced by pubchem.
In regards to claim(s) 1, 6, 10, 27, 50, 55, 101, 103, 108, 109, 111, 113, 114, Benenato and Schrader, as applied supra, is herein applied in its entirety for its teachings of a lipid nanoparticle composition.
Benenato et al. teach lipid nanoparticle compositions that may include RNA (abs) or mRNA (col. 73, ln. 41), ionizable lipids (col. 1, lns. 40-43), and polymers (col. 82, lns. 8-12), addressing claim 112.
Benenato does not teach CKK-E12 in claim 110.
Echelon-inc teaches that CKK-E12 is useful for delivery RNA-based therapeutics because of its low toxicity and selectivity for the liver (pgs. 1-2).
Since Benenato does not teach CKK-E12 in claim 110, one of ordinary skill in the art would have been led to use Echelon-inc’s teaching of CKK-E12 for delivery of RNA-based therapeutics. One of ordinary skill in the art would have been led to combine the teachings since Benenato teaches lipid nanoparticle compositions for delivery of mRNA and Echelon-inc teaches that CKK-E12 is commonly used because of its low toxicity and selectivity for the liver cells.
Response to Arguments
Applicant's arguments filed 12 February 2026 have been fully considered but they are not persuasive.
The Applicant argues that the claims are now commensurate in scope with the alleged unexpected results (Remarks, pgs. 6-8).
Applicant’s argument is not found persuasive. The Applicant shows encapsulation efficiency and stabilization when PVA/PVP is used, as opposed to when PVA/PVP is absent or sucrose/maltose buffer or PBS are used in the two declarations filed. The Applicant summarizes and alleges that the previously-filed declarations establish that after a drying and redissolution cycle, RNA in lipid nanoparticles remained encapsulated only when the nanoparticles were further encapsulated in a 1:1 mass ratio of PVA and PVP, but did not remain encapsulated when the additional encapsulation is absent (Remarks, pg. 7). The Supplemental Figures indicate that mRNA did not remain encapsulated after a cycle of drying and rehydrating when 1:1 PVA:PVP was not used to dry the nanoparticles. PVA and PVP are commonly used polymers known in the art to act as stabilizers and encapsulation efficiency for nanoparticles (Dixit, pgs. 302, 305). Furthermore, a 1:1 blend of PVA and PVP is suggested to provide stability due to the intermolecular interactions, especially in the context of biomaterials and drug delivery (El-Mohdy, pg. 2).
Additionally, the data provided in the declarations only appear to compare PVA/PVP at one mass ratio and do not compare PVA/PVP to other polymers but to different buffers. It is unclear why the Applicant is showing data comparing PVA/PVP to different buffers other than other polymers. It would be helpful for the Applicant to show more comparative data between different polymers and different mass ratios of PVA/PVP or other polymers. Therefore, it is unclear that the presence of PVA/PVP aiding in the encapsulation efficiency and stabilization of the lipid nanoparticles is surprising or unexpected without substantial comparative data.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Danielle Kim whose telephone number is (571)272-2035. The examiner can normally be reached M-F: 9-5 p.m. PST.
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/D.A.K./Examiner, Art Unit 1613
/ANDREW S ROSENTHAL/Primary Examiner, Art Unit 1613