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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 08/25/25 has been entered.
Response to Amendment
Applicant’s amendment filed on 08/25/25 has been entered. Claims 1-3, 5, 6, 15, and 16 are cancelled. Claims 17-18 are added. Claims 4, 7-14, 17, and 18 are pending. Claims 9-14 are withdrawn from consideration. Claims 4, 7, 8, 17, and 18 are examined herein. Applicant’s amendment/argument have overcome each and every objection set forth in Office Action mailed on 03/24/25.
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 17-18 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 determining of a ratio, comparing the ratio to a threshold, evaluating the quality. 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 comparing the ratio to a threshold and evaluating the quality, as drafted, is a process that, under its broadest reasonable interpretation, covers an abstract idea in the form of mental processes (i.e. mentally determining that a value is arbitrarily “good” or “bad”). (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 a generic recitation of delivery of the “good” product to a cell. 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, 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.
Claim Rejections - 35 USC § 112
Claims 4, 7-8, and 17-18 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.
Regarding claim 4, the claim recites “mixing the solution with a first substance”. There is insufficient antecedent basis for the term “the solution”. It is unclear if “the solution” recited in line 14 is referring to “a solution including the lipid particle group” in line 18.
Claims 7-8 and 17-18 are also rejected for being dependent on claim 4.
Claim Rejections - 35 USC § 103
Claim(s) 4, 7-8, and 17-18 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 ofPatel (Boosting Intracellular Delivery of Lipid Nanoparticle-Encapsulated mRNA, 2017).
Regarding claim 4, , 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 (siRNA-loaded lipid nanoparticles; hereinafter LNP) in a lipid particle group which contains a plurality of lipid particles:
comprising: mixing with a solution with 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 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, Zhu discloses the claimed invention as discussed above in claim 4. Zhu discloses the objective substance is nucleic acid (siRNA).
Regarding claim 8, 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, 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, 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 08/25/25 have been fully considered but they are not persuasive.
Regarding applicant’s first argument, the applicant argues the inclusion of “a threshold” set a practical limit to the application. Examiner respectfully disagrees. It is generally known in the art that for the purpose of evaluating a product and assigning a quality grade to the product (“Good” in the case of the application), the product must pass one or a series of criteria (thresholds). However, the claim, as drafted, does not provide any practical application or the purpose of the invention or how the threshold is being set/determined. As such, the threshold as claimed could be an arbitrary parameter set up by a person of ordinary skill in the art. Therefore, the limitation is not practically limiting as argued.
Regarding applicant’s second argument, the applicant argues that the judicial exception, the application of Formula (I), is distinct from the conventional technology available at a time, which applies an inclusion rate equation as argued in Page 8 of the remark. Examiner respectfully disagrees. MPEP 2106.05(f)(3) states “a claim having broad applicability across many fields of endeavor may not provide meaningful limitations that integrate a judicial exception into a practical application or amount to significantly more.” At the moment, calculated abundance ratio from Formula (I) is used to compare the threshold value, which is generically recited and not practically limiting as discussed above. Without recitation of how the threshold is being set in a non-abstract manner, the step of calculation after data gathering using Formula (I) as claimed is at best a mere instruction to apply an exception.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICKEY HUANG whose telephone number is (571)272-7690. The examiner can normally be reached M-F 9:30-5:30 PM ET.
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/M.H./Examiner, Art Unit 1758
/JILL A WARDEN/Supervisory Patent Examiner, Art Unit 1798