DETAILED ACTION
Status of the Claims
1. Claims 1-20 are pending.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
2. Claim(s) 1-3, 9-14 and 17 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Xu et al. (US 2005/0009004).
Claim 1 and 2. Xu et al. teach a method of characterizing nanovesicles comprising entrapping and sensing the dielectric properties of said nanovesicles using an electrical impedance sensing device (determining dielectric properties of particles such as vesicles or viruses by capturing the particle in the hole of chip and measuring impedance; [0097][0124][0317][0308][0385]).
Claim 3. Xu et al. teach the nanovesicles comprise exosomes (particles could be intracellular organelle of cells or cell fragment such as vesicles; [0119]).
Claim 9. Xu et al. teach the electrical impedance sensing device comprises two or more electrodes that apply an AC field across the trapped nanovesicles (electrodes are placed on either side of the hole to apply non-uniform electric field; [0025][00241] and Fig 6).
Claim 10. Xu et al. teach the AC field applies a field in the range of from about 500 KHz to about 50 MHz (non-uniform electric field has frequency in the range of 0.01kHz to about 500 MHz; [0241]).
Claim 11. Xu et al. teach the AC field is altered in magnitude and the results of the magnitude changes are analyzed to identify one or more biophysical dielectric properties of said exosomes (electric field is altered in magnitude and analyzed to determine dielectric properties of particles; [0238][0243].
Claim 12. Xu et al. teach the AC field is altered in phase and the results of the phase changes are analyzed to identify one or more dielectric properties of said exosomes (electric field is altered in phase and analyzed to determine dielectric properties of particles; [0238][0241][0243]). .
Claim 13. Xu et al. teach the AC field is altered in magnitude and phase and the results of the magnitude and phase changes are analyzed to identify one or more dielectric properties of said exosomes (electric field is altered in magnitude and phase and analyzed to determine dielectric properties of particles; [0238][0241[0243]).
Claim 14. Xu et al. teach the electrical impedance sensing device comprises an impedance analyzer, a power supply, a micromanipulator and a signal processor (impedance is measured;[0308], thus it is apparent impedance analyzer is present, a power source, electrodes and recording circuit/processor [0022][0025][0032 and Fig 6A).
Claim 17. Xu et al. teach the two or more electrodes are placed at a distance from each other between about 20 µm and 100 µm (two electrode are placed at distance apart; [0025] such as greater than about 30 microns and less than 10 centimeters [0036]).
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.
3. Claim(s) 1-8, 11, 15 and 16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Haandbaek et al. (Lab Chip, 2014, 369-377).
Claims 1-3, Haandbaek et al. teach method of characterizing cells with vacuoles comprising entrapping and sensing cells in the sensing region and measuring the dielectric properties using impedance cytometry (see abstract and Figs 1B and 1C and page 370 and page 374, col. 2). Haandbaek et al. do not explicitly teach characterizing nanovesicles but teaches measuring permittivity of vacuole and vacuole membrane (see Table 1) and further teaches the method is very general and can be used on other cells regardless of shape and internal complexity (see page 376, col. 2), therefore, it would have been obvious to one of ordinary skill in the art that Haandbaek et al. method could be easily applicable to nanovesicles such as liposomes and exosomes.
Claim 4. Haandbaek et al. teach the nanovesicles are liposomes and they are characterized by distinguishing between liposomes with different membrane compositions (cells are differentiate by membrane capacitance; see Table 1 and Fig 5).
Claim 5. Haandbaek et al. teach nanovesicles are liposomes and they are characterized by distinguishing between liposomes loaded with RNA and liposomes without RNA (yeast cells/exosomes are distinguished based on organelles present in cytoplasm; see page 374, col. 2).
Claim 6. Haandbaek et al. teach the exosomes are characterized by distinguishing between exosomes secreted from different cellular origins (yeast cells/exosomes are distinguished from wild type strain and KanMX strain; see page 374, col. 2).
Claim 7. Haandbaek et al. teach the exosomes are characterized by distinguishing between exosomes with different size distribution but secreted from the same cellular origins (different sizes of yeast cells/exosomes i.e. mother cell and daughter cell are distinguished originated from same strain; see page 373, col. 2).
Claim 8. Haandbaek et al. teach the exosomes are characterized by distinguishing between exosomes with different cytosolic compositions (yeast cells/exosomes are distinguished based on organelles present in cytoplasm; see page 374, col. 2).
Claim 11, Haandbaek et al. teach electric field is altered in magnitude and changes in magnitude to identify dielectric property of the yeast cells/ exosomes (see page 370, col. 1 and Fig 3).
Claims 15 and 16. Haandbaek et al. teach the dielectric properties of said exosomes comprise opacity magnitude (opacity magnitude is measured; see Fig 3).
Allowable Subject Matter
Claims 18-20 are allowed.
The following is a statement of reasons for the indication of allowable subject matter: Xu et al. teach a chip onto the recording cartridge, the bottom chamber (for example, the intracellular chamber) is first loaded with the intracellular solutions, the top chamber is loaded with extra-cellular solutions using a pipette. The cartridge is then loaded onto a microscope stage. Electrical connections from the intracellular electrodes and extracellular electrodes to the connections on the preamplifier head-stage are made. The resistance through the ion transport measuring holes is monitored with an AXON patch clamp amplifier [0564]. Xu et al. do not teach a nanopipette having first end located in the first chamber and second end located in second chamber and a first sensing electrode located adjacent to the tip and second sensing electrode located adjacent to tip and opposing to the first sensing electrode.
Claims 19 and 20 are allowed based on their dependency on claim 18.
Response to Arguments
Applicant's arguments filed 8/21/2025 have been fully considered but they are not persuasive. Applicant argues on page 1 of remarks that cited reference; Xu et al. does not teach sensing the dielectric properties of nanovesicles but teaches using dielectric properties of particles for moving into position so it can be measured for ion transport activity.
In response, examiner respectfully disagrees with applicant assertion. Xu et al. teaches embodiment of ion transport measuring means used to detect or measure cell recording/properties wherein cell is captured in a hole of a chip [0366] and recording electrode as shown in Fig 6 is used to measure variety of parameters such as resistance, voltage, current or impedance [0385][0308], thus Xu et al. teaches measuring dielectric properties of the cell with an electrode and meets claim limitation.
Applicant argues on page 2 of remarks that cited reference, Haandbaek et al. do not teach method that is capable of characterizing nanovesicles as claimed. Instead Haandbaek et al. teach method is capable of analyzing larger particles in a sensing region of 400 x 100 microns (see Fig 1) and thus Haandbaek sensing region is cannot be used for nanovesicles because channel signal ratio to noise ratio would be too high to generate useful data. In response, Haandback et al. teach in an alternative method, vacuole and vacuole membrane permittivity are measured (page 375, col. 1, paragraph 3 and Table 1) the cell and vacuole membranes are modeled using contact impedances (page 372, col. 2), thus Haandbaek sensing region is not limited to analyzing larger particles but also could be configured to detect nanovesicles as claimed.
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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/GURPREET KAUR/
Primary Examiner
Art Unit 1759