DETAILED CORRESPONDENCE
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
As to the claim amendments filed on 6/26/26, the previous 101 rejections are withdrawn.
Based on the claim amendments, the previous 112(b) rejections are withdrawn.
Regarding the claim amendments and remarks filed on 6/26/26, the previous prior art rejection has been modified to address the claim amendments (see below).
Claim Status
Claims 39-50, 52-58 are pending with claims 39-50, 52, 53 being examined and claims 54-58 deemed withdrawn.
Claim Rejections - 35 USC § 103
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 39-50, 52, 53 are rejected under 35 U.S.C. 103 as being unpatentable over Link et al (US 20180353913; hereinafter “Link”; already of record) in view of Pamula et al (US 20140193807; hereinafter “Pamula”; already of record)
As to claim 39 and 52, Link teaches a method of engulfing a particle into a droplet (Link; Fig. 1, [135]), the method using a microfluidic device comprising a droplet generator and a chamber, the chamber comprising a liquid medium, where the liquid medium is disposed on a voltage supply electrode and a ground electrode, wherein the method comprises: (a) dispensing a non-encapsulated particle and a droplet into the liquid medium; (b) dielectrophoretically trapping the particle and the droplet using the voltage supply electrode and the ground electrode, wherein the particle is trapped at or proximate to the voltage supply electrode, and wherein the particle is trapped between the voltage supply electrode and the droplet; and (c) increasing a supply voltage between the voltage supply electrode and the ground electrode to produce a dielecrophoretic force sufficient to move the droplet toward the voltage supply electrode while the particle remains at or proximate to the voltage supply electrode, thereby engulfing the particle into the droplet (Link teaches dispensing two droplets, one containing cells and one containing particles; Fig. 1, [135, 198]. The particles of Link are non-encapsulated in that they are not encapsulated with the cell particles, and/or that the particles have not been coalesced yet, where the coalescence of the particles is what encapsulates them. Link teaches that the particles and droplets are dispensed to the coalescence module; Fig. 1. Link teaches that the coalescence module includes 2 electrodes through which a voltage is applied across; [137-138, 140]. Link teaches that the electrodes are used for DEP to cause the droplets and cells/particles to be trapped/moved in the coalescence module by moving according to electric field; [136, 141]. Link teaches that the cells and droplets are then moved together to fuse/coalesce in the coalescence module, meaning that the droplet engulfs the cell/particle; [135, 145, 149]).
Link discloses that the voltage can be varied based on the particle and droplet composition, where particles and droplets move based on high or low field strength and based on their polarizability (Link; [141]). Link does not specifically teach step (d) of decreasing the voltage to eject the particle from the droplet or subjecting the ejected particle to steps (b) and (c) to re-engulf the particle in a droplet. However, Pamula teaches the analogous art of droplet manipulation where the particles are ejected from the droplet through a decrease in voltage and then the ejected particles are to steps (b) and (c) to re-engulf the particle in a droplet (Pamula teaches that electrodes are used to control movement, and Pamula teaches that the particles 1522 are ejected from droplet 1524 in step d and then the particles are re-engulfed in a droplet 1528 in step e or in a droplet 1530 in step f; Figs. 15, [135-141]. Pamela teaches particles 2515 is ejected from droplet in Fig. 25b/c and then re-engulfed in droplet 2520 in fig. 25c; Figs. 25, [180]. Pamela teaches that the electrodes for moving and trapping the particle have their electric fields altered to capture/eject the particle and also to move the droplet away from the particle, where some of these electrodes would have their voltage decreased during this process to control the movement the fluid. Pamula teaches that the electrodes are 1510/2510 whereby these electrodes have their voltage changed to move the droplet; Figs. 15, 25, [135-141, 180]. Therefore, because the droplet moves away from the electrode with the particle, the particle is ejected. The examiner notes that page 2 of the instant specification appears to recite the same operation of moving the droplet to accomplish the ejection of the particle). It would have been obvious to one of ordinary skill in the art to have modified the coalescing/engulfing step of Link to have including a splitting/ejecting and re-engulfing step as in Pamula because Pamula teaches that splitting/ejecting and re-engulfing the particle with a reagent droplet enables a further treatment of the particle (Pamula; [135-141, 180]), and one of ordinary skill in the art would have been further motivated to perform this process based on the desired treatment of the particle. If it is deemed that modified Link does not specifically teach that during ejection of the particle that the voltage supply is decreased, then Link does teach that the voltage can be varied where depending on the dielectric polarizability of the particles or fluid that the particles or fluid will either move towards high or low electric field, and also that various cells and fluids have different dielectric properties that depend on various factors (Link; [141]). It would have been obvious to a person having ordinary skill in the art to modify the voltage in modified Link during the separation/ejection process of Pamula to have a negative voltage to control particle or fluid movement since the voltages for the electric field are known to vary and depend on the dielectric properties of particles or fluid and the desired movement (Link; [141]). Therefore, it is evident that Link recognizes that the voltage increase/decrease is a result effective variable since the voltages of the electrodes can vary based on desired movement and since varying the voltage depends on the dielectric properties of particles or fluid and the desired movement (Link; [141]). Therefore, it would have been obvious to optimize modified Link’s voltage during splitting/ejecting of particles in Pamula to be negative depending on the cells being treated, the fluid used, and the type of particles used treatment being performed.
As to claim 40, Link teaches the method according to claim 39, wherein the liquid medium comprises, consists essentially of, or consists of an oil (Link teaches oil; [80, 87, 93, 95, 98, 99, 130]).
As to claim 41, Link teaches the method according to claim 39, wherein voltage supply electrode is transparent (Link teaches ITO which is transparent; [138]).
As to claim 42, Link teaches the method according to claim 39, wherein voltage supply electrode is an indium tin oxide (ITO) electrode (Link; [138]).
As to claim 43, Link teaches the method according to claim 39, wherein the particle is a microparticle or a cell (Link teaches a cell; [135, 198, 239, 236, 249, 269, 272]).
As to claim 44, Link teaches the method according to claim 39, wherein the method further comprises modifying the engulfed particle (Link teaches combining a cell as the particle with a droplet that has a reagent bead; [198]. Link teaches that fluorescent markers can be used to bind/modify to cells; [191-192]. Link also teaches other modifying reactions; [159, 160, 191, 236, 239, 249]).
As to claim 45, Link teaches the method according to claim 44, wherein the modifying comprises covalently or non-covalently attaching a molecule present in the droplet to the particle (Link teaches combining cells and droplets that include molecules; [135]. Link teaches that molecules can include polypeptides or polynucleotides; [260]. Link teaches combining a cell as the particle with a droplet that has a reagent bead; [198]. Link teaches that fluorescent markers can be used to bind/modify to cells; [191-192]. Link teaches various types of reporter modifications; [274]. Link also teaches other modifying reactions; [159, 160, 191, 236, 239, 249]).
As to claim 46, Link teaches the method according to claim 45, wherein the modifying comprises covalently or non-covalently attaching a nucleotide or polynucleotide present in the droplet to the particle (Link teaches combining cells and droplets that include molecules; [135]. Link teaches that molecules can include polypeptides or polynucleotides; [260]. Link teaches combining a cell as the particle with a droplet that has a reagent bead; [198]. Link teaches that fluorescent markers can be used to bind/modify to cells; [191-192]. Link teaches that nucleotides can be bound to the particle; [191]. Link teaches various types of reporter modifications; [274]. Link also teaches other modifying reactions; [226, 227, 244], see also [159, 160, 191, 236, 239, 249]).
As to claim 47, Link teaches the method according to claim 46, wherein the attaching comprises base-pairing the nucleotide or polynucleotide to a nucleotide or polynucleotide present on the particle prior to step (d) (The examiner is unclear of what step (d) is referring to. Link teaches the base pairing as part of the amplification/PCR process, see claim 46 above).
As to claim 48, Link teaches the method according to claim 45, wherein the modifying comprises covalently or non-covalently attaching an amino acid, polypeptide, sugar or carbohydrate present in the droplet to the particle (Link teaches pairing nucleotides during coalescing; [227]. Link teaches that molecules can include polypeptides or polynucleotides; [260]. Link teaches combining a cell as the particle with a droplet that has a reagent bead; [198]. Link teaches that fluorescent markers can be used to bind/modify to cells; [191-192]. Link teaches that nucleotides can be bound to the particle; [191]. Link teaches various types of reporter modifications; [274]. Link also teaches other modifying reactions; [226, 227, 244], see also [159, 160, 191, 236, 239, 249]).
As to claim 49, Link teaches the method according to claim 39, wherein the method further comprises imaging the engulfed particle at step (c) (Link teaches detection; [151], Fig. 1. Link also teaches detecting/assessing; [159, 160, 191, 236, 239, 249]. Link teaches image analysis during droplet formation; [221]. Link also teaches detection during engulfing process where once engulfing takes place then modifications are detected; [151, 215]. Link teaches determining characteristics of cells; [158, 160]. Link teaches that expression of polypeptides can be determined; [192]).
As to claim 50, Link teaches the method according to claim 49, wherein the particle is a cell, and wherein the method comprises imaging the cell to assess for expression of a polypeptide (Link teaches determining characteristics of cells; [158, 160]. Link teaches that expression of polypeptides can be determined; [192]).
As to claim 53, Link teaches the method according to claim 39, comprising imaging the particle during one or more or more of steps (a), (b), and (d) (Link teaches image analysis during droplet formation; [221]. Link also teaches detection during engulfing process where once engulfing takes place then modifications are detected; [151, 215]).
Other References Cited
The prior art of made of record and not relied upon is considered pertinent to applicant's disclosure include;
McEwen et al (US 20200171501; hereinafter “McEwen”; already of record) teaches a droplet 820 as a reagent and a microobject/cell 830/832; Fig. 9. McEwen teaches immiscible oil [328], a droplet with reagents such as nucleic acids for affinity with a microobject such as a cell; [329]. McEwen teaches that the droplets can includes various reagents such as proteins and nucleic acids [333]. McEwen teaches DEP [334], and teaches that the chambers of have DEP configurations [318] where the configuration of the chambers of Fig. 9 can be seen in figures 4-5 [171, 172] and also in Fig. 1E [158] and in Fig. 2 [177]. McEwen teaches changing the voltage [160].
Hunt et al (US 20100255556; hereinafter “Hunt”; already of record) teaches changing the electric field to merge/engulf or split/eject the particle and droplets from each other; Fig. 6, 7, [63-67], and [68, 74, 80, 86].
Response to Arguments
Applicant’s arguments filed on 6/26/26 have been considered but are moot because the arguments are towards the amended claims and not the current rejection. However, because the examiner is relying on the same prior art in the rejection then the examiner will address applicants’ arguments in order to advance prosecution.
Applicants argue on page 7 of their remarks that the particles of Link are encapsulated. The examiner respectfully disagrees. The particles of Link are non-encapsulated in that they are not encapsulated with the cell particles, and/or that the particles have not been coalesced yet, where the coalescence of the particles is what encapsulates them.
Applicants argue on page 7 of their remarks that Link teaches flow driven proximity and that the current methods incorporate a chamber in which the particle is immobilized at/on the electrode. However, the examiner disagrees and notes that the arguments are not commensurate to the scope of the claims. In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., a chamber and not a flow through system, and in which the particle is immobilized at/on the electrode) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Applicants argue on page 7 of their remarks that Link and Pamula do not teach decreasing the voltage to eject the particle. However, the examiner respectfully disagrees. The examiner notes that applicants have not provided any arguments towards the embodiment of Pamula in [135-141] and Figure 15. Further, the modification does teach the claimed decreasing the voltage to eject the particle. Link discloses that the voltage can be varied based on the particle and droplet composition, where particles and droplets move based on high or low field strength and based on their polarizability (Link; [141]). Link does not specifically teach step (d) of decreasing the voltage to eject the particle from the droplet or subjecting the ejected particle to steps (b) and (c) to re-engulf the particle in a droplet. However, Pamula teaches the analogous art of droplet manipulation where the particles are ejected from the droplet through a decrease in voltage and then the ejected particles are to steps (b) and (c) to re-engulf the particle in a droplet (Pamula teaches that electrodes are used to control movement, and Pamula teaches that the particles 1522 are ejected from droplet 1524 in step d and then the particles are re-engulfed in a droplet 1528 in step e or in a droplet 1530 in step f; Figs. 15, [135-141]. Pamela teaches particles 2515 is ejected from droplet in Fig. 25b/c and then re-engulfed in droplet 2520 in fig. 25c; Figs. 25, [180]. Pamela teaches that the electrodes for moving and trapping the particle have their electric fields altered to capture/eject the particle and also to move the droplet away from the particle, where some of these electrodes would have their voltage decreased during this process to control the movement the fluid. Pamula teaches that the electrodes are 1510/2510 whereby these electrodes have their voltage changed to move the droplet; Figs. 15, 25, [135-141, 180]. Therefore, because the droplet moves away from the electrode with the particle, the particle is ejected. The examiner notes that page 2 of the instant specification appears to recite the same operation of moving the droplet to accomplish the ejection of the particle). It would have been obvious to one of ordinary skill in the art to have modified the coalescing/engulfing step of Link to have including a splitting/ejecting and re-engulfing step as in Pamula because Pamula teaches that splitting/ejecting and re-engulfing the particle with a reagent droplet enables a further treatment of the particle (Pamula; [135-141, 180]), and one of ordinary skill in the art would have been further motivated to perform this process based on the desired treatment of the particle. If it is deemed that modified Link does not specifically teach that during ejection of the particle that the voltage supply is decreased, then Link does teach that the voltage can be varied where depending on the dielectric polarizability of the particles or fluid that the particles or fluid will either move towards high or low electric field, and also that various cells and fluids have different dielectric properties that depend on various factors (Link; [141]). It would have been obvious to a person having ordinary skill in the art to modify the voltage in modified Link during the separation/ejection process of Pamula to have a negative voltage to control particle or fluid movement since the voltages for the electric field are known to vary and depend on the dielectric properties of particles or fluid and the desired movement (Link; [141]). Therefore, it is evident that Link recognizes that the voltage increase/decrease is a result effective variable since the voltages of the electrodes can vary based on desired movement and since varying the voltage depends on the dielectric properties of particles or fluid and the desired movement (Link; [141]). Therefore, it would have been obvious to optimize modified Link’s voltage during splitting/ejecting of particles in Pamula to be negative depending on the cells being treated, the fluid used, and the type of particles used treatment being performed.
Applicants argue on pages 8-9 that and that there is no motivation to combine Pamula with Link and that the proposed modification would change the principle of operation. However, the examiner respectfully disagrees. The examiner maintains that Pamula does not exclusively recite a stationary platform because Pamula teaches moving droplets via electrodes. Pamula teaches that the electrodes are 1510/2510 whereby these electrodes have their voltage changed to move the droplet; Figs. 15, 25, [135-141, 180]. Therefore, because the droplet moves away from the electrode with the particle, the particle is ejected. The examiner notes that page 2 of the instant specification appears to recite the same operation of moving the droplet to accomplish the ejection of the particle. Because Link uses electrodes to engulf/coalesce particles via movement and dielectric control then including the movement of droplets via the electrodes of Pamula would not change the operation of Link. The examiner maintains that there is motivation to combine. It would have been obvious to one of ordinary skill in the art to have modified the coalescing/engulfing step of Link to have including a splitting/ejecting and re-engulfing step as in Pamula because Pamula teaches that splitting/ejecting and re-engulfing the particle with a reagent droplet enables a further treatment of the particle (Pamula; [135-141, 180]), and one of ordinary skill in the art would have been further motivated to perform this process based on the desired treatment of the particle. If it is deemed that modified Link does not specifically teach that during ejection of the particle that the voltage supply is decreased, then Link does teach that the voltage can be varied where depending on the dielectric polarizability of the particles or fluid that the particles or fluid will either move towards high or low electric field, and also that various cells and fluids have different dielectric properties that depend on various factors (Link; [141]). It would have been obvious to a person having ordinary skill in the art to modify the voltage in modified Link during the separation/ejection process of Pamula to have a negative voltage to control particle or fluid movement since the voltages for the electric field are known to vary and depend on the dielectric properties of particles or fluid and the desired movement (Link; [141]). Therefore, it is evident that Link recognizes that the voltage increase/decrease is a result effective variable since the voltages of the electrodes can vary based on desired movement and since varying the voltage depends on the dielectric properties of particles or fluid and the desired movement (Link; [141]). Therefore, it would have been obvious to optimize modified Link’s voltage during splitting/ejecting of particles in Pamula to be negative depending on the cells being treated, the fluid used, and the type of particles used treatment being performed.
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 BENJAMIN R WHATLEY whose telephone number is (571)272-9892. The examiner can normally be reached Mon- Fri 8am-5pm.
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/Benjamin R Whatley/Primary Examiner, Art Unit 1798
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