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 .
Response to Amendment
Applicant’s amendment filed on 06/22/26 has been entered. Claim 19 is added. Claims 9-14 remain withdrawn. Claims 4, 7-8, and 17-18 are examined herein. Applicant’s amendment and remark have overcome each and every rejection under 112(b) in Office Action mailed on 09/23/25.
Claim Rejections - 35 USC § 112
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.
Claims 4, 7, and 17-19 is/are 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 4 recites a “determining a correlation index of a delivery efficiency of the objective substance to the cell relative to an abundance ratio of the first lipid particles in the lipid particle group. Applicant cites line 27, page 7-line 13, page 9 for support. Though the specifications disclose abundance ratio being used an index, it is not clear if this is indeed the claimed correlation index since the claim does not disclose how the index is being used after being determined. Furthermore, the claim recites another step of determining the abundance ratio after the correlation index and comparing the determined abundance ratio to a threshold (which is unclear if the threshold is the correlation index. This indicates the correlation index is a value distinct from the abundance ratio. As there is no support for the correlation index, the subject matter is determined to be new matter.
Dependent claims 7 and 17-19 are also being rejected for failing to cure the deficiency of claim 4.
Claim Rejections - 35 USC § 101
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 4, 7-8 and 17-19 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more.
Regarding claim 4, the claim recites steps of determining an index and an abundance ratio and comparing the ratio to a threshold. The claim later recites that the determination of the ratio includes calculating based on data collected.
The limitation of determination of a ratio based on calculation from data collected, as drafted, is a process that, under its broadest reasonable interpretation, covers an abstract idea in the form of mathematical concept. (Step 2A, Prong 1).
The limitation of determination of an index and comparing the ratio to a threshold, as drafted, is a process that, under its broadest reasonable interpretation, covers an abstract idea in the form of mental processes”) (Step 2A, Prong 1).
This judicial exception is not integrated into a practical application because after the evaluation is completed, nothing is done with the information other than selecting a product that passes the threshold. Therefore, there is no integration of the information produced/determined much less a practical one after the information is obtained. Accordingly, this does not integrate the abstract idea into a practical application because it does not impose any meaningful limits on practicing the abstract idea (Step 2A, Prong 2).
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because preparing sample and lipid particles(first having a substance encapsulated, second not containing the substance), irradiating the sample and acquiring experimental data (before the abstract idea) appears to be routine and convention ways of collecting data using light scattering or fluorescence analysis. Routine and conventional ways of collecting data from known source/database cannot provide an inventive concept. The claim is not patent eligible. See MPEP 2106.05(g). (Step 2B)
Regarding claims 7-8, the claim(s) recite(s) the identity of the objective substance and the size of the lipid particles. Specifying the identity of the sample or the size of the sample does not appear to be an inventive step. The claims are not patent eligible.
Regarding claim 17-18, the claim(s) recite(s) the numbers of particles are measured using the intensity/momentum of scattered light as an index/device for measuring the number of particles. The claim does not cure the deficiency highlighted above. The claim simply further recites how the device (scatter light or fluorescence) functions in obtaining the number of particles (acquiring experimental data). Accordingly, routine and conventional ways of collecting data cannot provide an inventive concept. The claims are not patent eligible.
Regarding claim 19, the claim(s) recite(s) a step of administering the product selected for delivery of the objective substance to the cell to a person in need of the objective substance. This does not cure the deficiency. This limitation is recited at such a high level of generality that it does not recite any form of treatment or administration (injection, oral, etc.) or any specific requirement for the individual or patient for receiving the substance, making the limitation nominal at best.
Claim Rejections - 35 USC § 103
Claim(s) 4, 7-8, and 17-19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zhu (Light-Scattering Detection below the Level of Single Fluorescent Molecules for High-Resolution Characterization of Functional Nanoparticles, 2014; cited in previous OA) in view of Patel (Boosting Intracellular Delivery of Lipid Nanoparticle-Encapsulated mRNA, 2017).
Regarding claims 4 and 19, Zhu (Light-Scattering Detection below the Level of Single Fluorescent Molecules for High-Resolution Characterization of Functional Nanoparticles, 2014), discloses an analysis method for determining quantity of first lipid particles containing an objective substance encapsulated within a lipid membrane (siRNA-loaded lipid nanoparticles; hereinafter LNP) in a lipid particle group which contains a plurality of lipid particles:
comprising: mixing a solution of the lipid particle group being analyzed for quality with a first substance, wherein
a first substance which has a lipid membrane permeability (SYTO 82) which binds to the objective substance (Si-RNA), and includes a dye that generates fluorescence (SYTO 82, a cell-permeant dye that labels nucleic acids; 11004) (Staining of siRNA-Loaded Lipid Nanoparticles, 11005);
irradiating a solution including the lipid particle group with light (laser, Figure 1a) (We implemented HSFCM to characterize siRNA-loaded LNPs with the same composition as those currently being used in clinical test…the empty and siRNA-loaded LNP samples were analyzed upon fluorescent staining with SYTO 82, a cell-permeant dye that labels nucleic acids.) (Page 11003, right col., paragraph 1-Page 11004, left col., paragraph 1);
calculating the total number of the lipid particle group (the particle concentration of siRNA-loaded LNPs (with an siRNA concentration of 0.1 mg/mL) was measured to be 7.0 x 1012 particles/mL (Figure 5a); characterization is done by HSFCM (a flow cytometer); 11004) and determining a fraction of SiRNA loading (the fraction of siRNA loading was determined to be approximately 100%. 11004), wherein the first measuring step is total number of lipid particle is detected be scattered light (Light-scattering detection of single particles in the low nanometer range using HSFCM; Figure 2; every single particle is counted once)
and calculating a number of the first lipid particles, wherein the measuring of the first lipid particles is detected by fluorescence (siRNA-loaded LNP samples were analyzed upon fluorescent staining with SYTO 82, a cell-permeant dye that labels nucleic acid…the fraction of siRNA loading was determined to be approximately 100%. Page 11003) (all of the siRNA sample are nanoparticles encapsulated with si-RNA).
Zhu does not explicitly disclose the comparison step and contacting/delivering step. Zhu is concerned with developing nanodelivery vectors (Through concurrent fluorescence detection, quantitative multiparameter characterization of clinical nanomedicine is demonstrated through investigations of doxorubicin encapsulated liposomes and small interfering RNA (siRNA)-loaded lipid nanoparticles. page 10999). Therefore, it would have been obvious for one of ordinary skill in the art to have used the method to assess encapsulation characteristics of the particles, with those sample with desired and acceptable encapsulation % and characteristics being determined to be suitable for use (read as claimed contacting the cells).
Though Zhu does not explicitly disclose the formula (I), Zhu discloses determining the total number of si-RNA loaded sample (regardless if the samples have si-RNA or not) using light scattering and a second number of analyzing amount of si-RNA loaded sample that actually contains si-RNA (which was determined to be “approximately 100%. Page 11003”. As such, the abundance ratio and encapsulation efficiency based on the formula of Patel (II. Lipid-Based Nanoparticles (LNPs), Particle Characterization) would have been equal to each other equaling to 1.
Regarding claim 7, Modified Zhu discloses the claimed invention as discussed above in claim 4. Zhu discloses the objective substance is nucleic acid (siRNA).
Regarding claim 8, Modified Zhu discloses the claimed invention as discussed above in claim 4. Zhu discloses the plurality of lipid particles have a particle size of less than 1 micrometers (45 to 54 nm) (page 11004, left col., first paragraph).
Regarding claim 17, Modified Zhu discloses the claimed invention as discussed above in claim 4. Zhu discloses the number of the first lipid particles and the number of the second lipid particles are measured using an intensity as an index (HSFCM produces intensity/peak during detection; see peaks in Figure 5).
Regarding claim 18, Modified Zhu discloses the claimed invention as discussed above in claim 4. Zhu discloses the number of the first lipid particles and the number of the number of the second lipid particles are measured using a DLS (See Figure 5d, SS--which stands for side scattering--burst area to events) (Even though SS is primarily used for particle size, SS notes each particle as distinct event as seen in dots on the chart bivariate dot-plot represents a distinct event/particle of Figure 5d, thus the total number can be found).
Response to Arguments
Applicant's arguments filed 06/22/26 have been fully considered but they are not persuasive. Regarding applicant’s argument with the prior art rejection in pages 13-14, the argument is directed to a newly amended matter that is determined to be new matter. As such, the argument is moot until the issue has been resolved.
Specifically, regarding the 101 rejection, other than the issue of correlation index, which is considered as a new matter, the claim and argument is directed toward the calculation being unconventional (para. 1-3, page 12), however the claim limitation is not practically integrated as step of “selecting” or “administering” is recited in such a high level of generality that it does not recite any form of treatment or administration (injection, oral, etc.) or any specific requirement for the individual or patient for receiving the substance, making the limitation nominal at best.
Conclusion
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.
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/M.H./ Examiner, Art Unit 1758
/REBECCA M FRITCHMAN/ Primary Examiner, Art Unit 1758
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