DETAILED ACTION
The amendment filed on 02/25/2026 has been entered and fully considered. Claims 1-5, 7, 10-15, 17, 19, 21, 26-28 and 30-31 are pending. Claims 1-5, 7, 10-15, 17, 19 and 21 have been withdrawn from consideration. Claims 26-28 and 30-31 are considered on merits, of which claim 26 is amended.
Response to Amendment
In response to amendment, the examiner modifies rejection over the prior art established in the previous Office 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 .
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim(s) 26-28 and 30 is/are rejected under 35 U.S.C. 103 as being unpatentable over Petrocellis et al. (British Journal of Pharmacology, 2011) (Petrocellis) in view of Gomes et al. (Cell Calcium, 1998) (Gomes) and Li et al. (Analytical Chemistry, 2005) (Li).
Regarding claim 26, Petrocellis teaches a method of determining an effect of one or more Cannabis-derived compounds on intracellular calcium concentration in a cell (page 1481), the method comprising:
isolating a cell (HEK-293 cells) (page 1481, par 4);
measuring fluorescence of the cell to determine a background fluorescence (Fmin) (page 1481, par 4);
adding a cell-permeable fluorescent calcium indicator (Fluo-4AM) to a reservoir in the device (page 1481, par 4);
measuring fluorescence of the cell and determining a first intracellular calcium concentration in the cell based on the fluorescence of the cell (page 1481, par 4);
adding the one or more Cannabis-derived compounds to the reservoir in the microfluidic device (page 1481, par 4);
measuring fluorescence of the cell and determining a second intracellular calcium concentration in the cell based on the fluorescence of the cell (page 1481, par 4);
adding ionomycin to the cell (page 1481, par 4);
measuring fluorescence of the cell to determine a maximum fluorescence (Fmax) (page 1481, par 4); and
comparing the first intracellular calcium concentration to the second intracellular calcium concentration to determine the effect of the one or more Cannabis-derived compounds on intracellular calcium concentration in the cell (page 1481, par 4).
While Petrocellis teaches measuring all parameters of the equation 1, Petrocellis does not explicitly mention the equation 1 as recited in the claim. However, Gomes teaches using the equation 1 to calculate intracellular calcium concentration in the cell based on the fluorescence of the cell (Summary). It would have been obvious to one of ordinary skill in the art to use the equation 1 for determining intracellular calcium concentration in the cell based on the fluorescence of the cell as taught by Gomes, because Petrocellis has measured all the parameters in the equation 1, the result is predictable.
Petrocellis does not specifically teach isolating a single cell in a cell retention structure in a chamber of a microfluidic device, the chamber in fluid communication with: (a) a first reservoir via a first channel. wherein the first reservoir is for introducing the single cell into the chamber and for washing: (b) a second reservoir via a second channel. wherein the second reservoir is for reagent delivery: and (c) a third reservoir via a third channel. wherein the third reservoir is a waste reservoir, wherein a depth of the channels is less than a depth of the reservoirs. However, Li teaches isolating a single cell in a cell retention structure in a chamber of a microfluidic device, the chamber in fluid communication with: (a) a first reservoir via a first channel, wherein the first reservoir is for introducing the single cell into the chamber and for washing: (b) a second reservoir via a second channel. wherein the second reservoir is for reagent delivery: and (c) a third reservoir via a third channel. wherein the third reservoir is a waste reservoir (Fig.1, page 4381, par 0), wherein a depth of the channels is less than a depth of the reservoirs (Fig. 1). Li teaches that “In this work, we developed a microfluidic method to study the contraction of a single cardiac myocyte. This method integrates on the chip the following operations: single-cell selection, cell retention, dye loading, chemical stimulation, fluorescence measurement, and quantitative analysis of intracellular calcium concentrations. Our on-chip dye loading method can minimize the damage to the cells by avoiding the use of the centrifuge. This provides an improved method to perform cellular analysis of fragile cells” (page 4321, par 9-10). It would have been obvious to one of ordinary skill in the art to isolate a single cell in a cell retention structure in a chamber of a microfluidic device, the chamber in fluid communication with: (a) a first reservoir via a first channel. wherein the first reservoir is for introducing the single cell into the chamber and for washing: (b) a second reservoir via a second channel. wherein the second reservoir is for reagent delivery: and (c) a third reservoir via a third channel. wherein the third reservoir is a waste reservoir, wherein a depth of the channels is less than a depth of the reservoirs, in order to provide an improved method to perform cellular analysis of fragile cells.
Petrocellis does not specifically teach measuring fluorescence of the background when the cell is out of an aperture of the optical imaging and fluorescent measurement system (Fmin) by moving the microfluidic device. However, Li teaches measuring fluorescence of the background when the cell is out of an aperture of the optical imaging and fluorescent measurement system (Fmin) by moving the microfluidic device (page 4321, par 3-4). It would have been obvious to one of ordinary kill in the art to measure fluorescence of the background when the cell is out of an aperture of the optical imaging and fluorescent measurement system (Fmin) by moving the microfluidic device, in order to correct for fluorescence of the background.
Regarding claim 27, Petrocellis teaches that wherein the Cannabis-derived compounds are cannabinoids and/or terpenes (page 1481, par 4).
Regarding claim 28, Petrocellis teaches that wherein the Cannabis-derived compound is CBD or CBD and myrcene (page 1481, par 3).
Regarding claim 30, Petrocellis teaches that wherein the cellpermeable fluorescent calcium indicator is Fluo-4 acetoxymethyl ester (Fluo-4 AM) (page 1481, par 4).
Claim(s) 31 is/are rejected under 35 U.S.C. 103 as being unpatentable over Petrocellis in view of Gomes and Li as applied to claims 26-28 and 30 above, and further in view of Massi et al. (The Journal of Pharmacology and Experimental Therapeutics, 2004) (Massi).
Regarding claim 31, Petrocellis references Massi for studying antitumor effect of cannabinoid on human glioma cell lines (page 1480, par 2). Thus, it would have been obvious to one of ordinary skill in the art to apply Petrocellis’s method to a glioma cell, in order to determine an effect of one or more Cannabis-derived compounds on intracellular calcium concentration in a glioma cell.
Response to Arguments
Applicant’s arguments with respect to claim(s) 26 have been considered but are moot in view of new ground of rejection.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to XIAOYUN R XU, Ph. D. whose telephone number is (571)270-5560. The examiner can normally be reached M-F 8am-5pm.
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/XIAOYUN R XU, Ph.D./ Primary Examiner, Art Unit 1797