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As to the claim amendments and remarks filed on 12/17/25, most of the previous 112b rejections are withdrawn. However, some rejections remain.
Regarding the claim amendments and remarks, the previous prior art rejection has been modified to address the claim amendments (see below).
Claim Status
Claims 1-4, 7-8, 10-11, 14-20 are pending with claims 1-4, 7-8, 10-11, 14 being examined and claims 15-20 deemed withdrawn.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 8, 10-11 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 pre-AIA the applicant regards as the invention.
As to claim 8, it is unclear what the difference in “a flow-focusing structure” of claim 8 is when compared to the newly amended “a flow-focusing structure” of claim 1. The claim is drafted in such a way that this implies there are distinct and separate “flow focusing structures”, but the examiner believes they are the same structure, and therefore the antecedent basis is incorrect. Further, it is unclear as to applicants intent and a potential infringer would not understand whether there are multiple structures required in claim 8 or whether claim 8 is referring to back to the previously recited structure.
Claim 10 recites that the encapsulation ratio is improved, which is unclear. Specifically, what is the encapsulation ratio improved with respect to? In this claim, an improvement is some type of comparison that conveys relativity, yet it is unclear what the baseline comparison is with respect to.
Claim 11 recites that the encapsulation ratio is suppressed, which is unclear. Specifically, what is the encapsulation ratio suppressed with respect to? In this claim, a suppression is some type of comparison that conveys relativity, yet it is unclear what the baseline comparison is with respect to.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-3, 7-8, 10, 11, 14 are rejected under 35 U.S.C. 102a1/a2 as being anticipated by Amini et al (US 20170128940; hereinafter “Amini”).
As to claim 1, Amini teaches a system for quantitative control of mitochondrial transfer based on droplet microfluidics (Amini teaches a system for droplet microfluidics; [3], Figs. 1, 3, 5-9), comprising:
a droplet generation module configured to generate droplets containing isolated mitochondria and a single recipient cell, wherein the isolated mitochondria are engulfed within the single recipient cell via endocytosis; wherein the droplet generation module comprises: a first inlet configured to receive a recipient cell suspension comprising a plurality of single recipient cells; a second inlet configured to receive an isolated mitochondria suspension comprising isolated mitochondria; a third inlet configured to receive a surfactant-added fluorinated oil, wherein the recipient cell suspension and the isolated mitochondria suspension collectively form an aqueous phase, and the surfactant-added fluorinated oil forms an oil phase; a flow-focusing structure configured to generate the droplets; and a serpentine structure positioned upstream of the flow-focusing structure and configured to align randomly distributed recipient cells into a single-cell streamline; wherein the flow-rate ratio of the oil/water phase is 6; a droplet observation module configured for observation of the generated droplets under a microscope (Amini teaches the droplet generation module defined by three inlets 302/102, 306/106, 312/112 and their corresponding channels to where the channels meet; Fig. 1, 3, [45]. Amini teaches droplet generation region has a flow focusing structure in the region of 126 that generates the droplets; [45], Fig. 1. See also figures 5-9 which show variations of the device. The examiner notes that how mitochondria are engulfed or interact with cells, and what the inlets are configured to receive is a matter of intended use, and further notes that the recipient cell and cell suspension, mitochondria, and oil are not positively recited as part of the system and do not further limit the structure beyond that of a capability. Amini teaches the droplet generation module includes mitochondrial recipient cell suspension as the cells that are used, and teaches incorporating particles in the droplets with the cells where the particles can be various molecular complexes; [11, 32, 35, 159]. Amini teaches the oil includes a surfactant; [165]. Amini teaches that channel 108/110 or 308/310 (or channels 104/304, 114/314) can be serpentine with a focusing length which helps to focus/align the components in the channels; [11, 40, 67-69], Figs. 1, 3, 4. See also Figs. 5-9. Amini teaches that channel 304/104 can also be curved; [65-66]. The flow rate ratio of the oil/water is a matter of intended use and Amini is capable of varying the flow rates; [63, 72, 83]. Amini teaches an observation module as the region of space between junction and outlet; Fig. 1, 3. The examiner notes that the observation module is just a region of space enabling observation to take place. See also figures 5-9 which show variations of the device, where figure 9 shows that the droplets are observed downstream of the formation); and
a droplet collection module configured to collect the generated droplets (Amini teaches the collection module 318/118; Fig. 1, 3, [40, 45]. The examiner notes that the collection module is just a region of space enabling collection to take place. See also figures 5-9 which show variations of the device.); wherein the droplets have a diameter equal to or less than 40 um (This limitation is related to intended use and function, and does not further limit the apparatus structure. As best understood, the droplet, mitochondria, and cell are not positively recited, and therefore the limitations do not further limit the apparatus beyond that of a capability. Amini teaches cells being used, and it is known that the average cell diameter can vary based on the cell from around 10-30 um, and therefore the single cell used would have a diameter of less than 40 um based on the type of cell used. Alternatively, Amini teaches a channel height of 0.5 um to 200 um, and with various aspect ratios such that the width is also within these dimensions, and therefore Amini teaches that the height and width can be less than 40 um, which would create a 40 um droplet; [71]. Amini teaches that channel sizes and geometries can be used; [72]. Amini also teaches that the channel size and particle size can be varied; [42]); and wherein an efficiency of mitochondrial transfer is at least 75% (This limitation is related to intended use and function, and does not further limit the apparatus structure. As best understood, the droplet, mitochondria, and cell are not positively recited, and therefore the limitations do not further limit the apparatus beyond that of a capability. The system of Amini is capable of using mitochondria and meeting this limitation as Amini teaches capturing cells and particles in droplets and where the particles can be various molecular complexes; [32, 159]. The instant application states that the transfer efficiency is based on the quality of mitochondria in [3] and Amini is capable of using high quality mitochondria. The instant application in [33] also states that the droplet size is related to the transfer efficiency where Amini is capable of forming various sized droplets; [71, 72]. The instant application in [35] and Figures 4 also states that the transfer efficiency is based on the number of mitochondria within the droplet, and Amini is capable of varying the number of particles/mitochondria in the droplet by varying the concentration and flow rate).
Note: The instant Claims contain a large amount of functional language (ex: “for…”, “configured to…”). However, functional language does not add any further structure to an apparatus beyond a capability. Apparatus claims must distinguish over the prior art in terms of structure rather than function (see MPEP 2114 and 2173.05(g)). Therefore, if the prior art structure is capable of performing the function, then the prior art meets the limitation in the claims.
As to claim 2, Amini teaches the system according to claim 1 (see above), wherein the droplet generation and observation modules are connected by a conduit (Amini teaches that a conduit channel is connecting the modules formed by the junction and the region of space after the junction; Figs. 1, 3, 5-9).
As to claim 3, Amini teaches the system according to claim 1 (see above), wherein the system is disposed on a chip (Amini; Figs. 1, 3, 5-9, [56]).
As to claim 7, Amini teaches the system according to claim 1 (see above), wherein the single recipient cell is recipient C2C12 cell (The examiner notes that the single recipient cells are not positively recited as part of the system, and therefore what the cells are defined by is functional/intended use and does not further limit the system structure beyond that of a capability. The system of the prior art is capable of using any cell. Amini teaches the droplet generation module includes mitochondrial recipient cell suspension as the cells that are used, and teaches incorporating particles in the droplets with the cells where the particles can be various molecular complexes; [11, 32, 35, 159]).
As to claim 8, Amini teaches the system according to claim 1 (see above), wherein the droplet generation module comprises a flow-focusing structure configured to separate the mitochondrial recipient cell suspension and the isolated mitochondria suspension into droplets (As best understood, Han teaches the flow focusing structure in claim 1 above. As best understood, Amini teaches flow focusing as the region of space at junction 126 where the oil is focused to create droplets, and also other focusing structures; Fig. 1, [35, 41, 45, 46, 47], See also Figs. 3, 5-9).
As to claim 10, Amini teaches the system according to claim 1 (see above), wherein the serpentine structure is configured to improve the ratio of encapsulating the single recipient cell in the droplet more than 47% (Amini teaches that channel 108/110 or 308/310 (or channels 104/304, 114/314) can be serpentine with a focusing length which helps to focus/align the components in the channels; [11, 40, 67-69], Figs. 1, 3, 4. See also Figs. 5-9. Amini teaches that channel 304/104 can also be serpentine; [65-66]. Amini shows in figure 4A the curve that achieves the focusing such that single particles/cells are ordered; Fig. 4. Amini teaches that this helps to achieve the function of 1 cell and 1 bead/particle per droplet; [38, 39, 75,89]. Applicants teach the serpentine structure itself is what focusses the cells to improve single cell encapsulation ratio and suppress the multiple cell encapsulation ratio; see [37] of the instant specification. Therefore, the presence of a serpentine structure that focuses cells is the structure that appears to achieve the claimed function/property, and any serpentine structure that was capable of focusing would be expected to behave the same, and Amini teaches the serpentine structure for focusing as seen above). When the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, the prior art products necessarily possess the characteristics of the claimed product. See MPEP 2112.01. As stated in In re Best, 562 F.2d 1252, 1255 (CCPA 1977): Where, as here, the claimed and prior art products are identical or substantially identical, or are produced by identical or substantially identical processes, the PTO can require an applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his claimed product. Whether the rejection is based on “inherency” under 35 U.S.C. § 102, on “prima facie obviousness” under 35 U.S.C. § 103, jointly or alternatively, the burden of proof is the same, and its fairness is evidenced by the PTO’s inability to manufacture products or to obtain and compare prior art products. See MPEP 2112.
As to claim 11, Amini teaches the system according to claim 1 (see above), wherein the serpentine structure is configured to suppress the ratio of encapsulating multiple recipient cells in the droplet less than 6% (Amini teaches that channel 108/110 or 308/310 (or channels 104/304, 114/314) can be serpentine with a focusing length which helps to focus/align the components in the channels; [11, 40, 67-69], Figs. 1, 3, 4. See also Figs. 5-9. Amini teaches that channel 304/104 can also be serpentine; [65-66]. Amini shows in figure 4A the curve that achieves the focusing such that single particles/cells are ordered; Fig. 4. Amini teaches that this helps to achieve the function of 1 cell and 1 bead/particle per droplet; [38, 39, 75,89]. Applicants teach the serpentine structure itself is what focusses the cells to improve single cell encapsulation ratio and suppress the multiple cell encapsulation ratio; see [37] of the instant specification. Therefore, the presence of a serpentine structure that focuses cells is the structure that appears to achieve the claimed function/property, and any serpentine structure that was capable of focusing would be expected to behave the same, and Amini teaches the serpentine structure for focusing as seen above). When the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, the prior art products necessarily possess the characteristics of the claimed product. See MPEP 2112.01. As stated in In re Best, 562 F.2d 1252, 1255 (CCPA 1977): Where, as here, the claimed and prior art products are identical or substantially identical, or are produced by identical or substantially identical processes, the PTO can require an applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his claimed product. Whether the rejection is based on “inherency” under 35 U.S.C. § 102, on “prima facie obviousness” under 35 U.S.C. § 103, jointly or alternatively, the burden of proof is the same, and its fairness is evidenced by the PTO’s inability to manufacture products or to obtain and compare prior art products. See MPEP 2112.
As to claim 14, Amini teaches the system according to claim 1 (see above), wherein the system is configured to yield at least 2x 106 recipient cells in the droplets for mitochondria transfer in 30 minutes (This limitation is related to intended use and function, and does not further limit the apparatus structure. Amini teaches creating roughly 2000 droplets/sec, and also 4000 droplets/sec; [174, 177]. Amini teaches that there is at least 1 cell/droplet; [38, 39, 75, 76]. At a rate of 2000 droplet/sec, then 3.6 x10^6 droplets would be formed in 30 minutes, and since there is at least 1 cell/droplet, then Amini teaches this limitation. Additionally, the number of cells created is based on the number of cells used in the input solution, the size of the channels, and the flow rate, all of which Amini is capable of).
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.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Amini et al (US 20170128940; hereinafter “Amini”; already of record) in view of Microfluidic Chip Shop (Microfluidic Chip Shop, Lab-on-a-chip Catalogue; published 10/2019; hereinafter "Chip Shop"; already of record).
As to claim 4, Amini teaches the system according to claim 3, with the chip (see above).
Amini does not specifically teach wherein the chip is smaller than 8 cm in length. However, Chip Shop teaches the analogous art of microfluidic chips having various configurations wherein the chip is smaller than 8 cm in length (Chip Shop teaches chips for droplet generation, where the chips are shown to scale and are smaller than 8 cm; p. 73, 76, 77. See also pages 43, 81 where the length is 7.5 cm). It would have been obvious to one of ordinary skill in the art to have modified the microfluidic chip for generating droplets of Amini to have been formed on a slide an less than 8 cm in length as in Chip Shop because Chip Shop teaches that microfluidics are known to be made on slides and also at dimensions smaller than 8 cm (Chip Shop; p. 73, 76, 77, 43, 81).
Claims 1-3, 7-8, 10, 11, 14 are rejected under 35 U.S.C. 103 as being unpatentable over Han et al (US 20220364120; hereinafter “Han”; already of record) in view of Amini et al (US 20170128940; hereinafter “Amini”; already of record).
As to claim 1, Han teaches a system for quantitative control of mitochondrial transfer based on droplet microfluidics (Han; Title), comprising:
a droplet generation module configured to generate droplets containing isolated mitochondria and a single recipient cell, wherein the isolated mitochondria are engulfed within the single recipient cell via endocytosis; wherein the droplet generation module comprises: a first inlet configured to receive a recipient cell suspension comprising a plurality of single recipient cells; a second inlet configured to receive an isolated mitochondria suspension comprising isolated mitochondria; a third inlet configured to receive a surfactant-added fluorinated oil, wherein the recipient cell suspension and the isolated mitochondria suspension collectively form an aqueous phase, and the surfactant-added fluorinated oil forms an oil phase; a flow-focusing structure configured to generate the droplets; wherein the flow-rate ratio of the oil/water phase is 6; a droplet observation module configured for observation of the generated droplets under a microscope (Han teaches three inlets; Figs. 1, 5, 8, [92]. Han teaches a droplet formation section that is a flow focusing structure converging channels to form droplets; Fig. 8. See also Figs. 1, 4, 5. The examiner notes that what the inlets are configured to receive is a matter of intended use, and further notes that the recipient cell and cell suspension, mitochondria, and oil are not positively recited as part of the system and do not further limit the structure beyond that of a capability. Han teaches the mixing of donor particles and target/recipient cells, where the particles can be small molecules and the target particles can be cells; [12, 15]. Han teaches that there are recipient cells through which genetic material is transferred; [74-79, 87]. Han teaches fluorinated oil with surfactant; [92]. Han teaches the observation module in the right side in section 5 of figure 8; [92]. The examiner notes that the observation module is just a region of space enabling observation to take place. See also Figs. 1, 4, 5, [66]. Han also teaches evaluation/observation; [48, 49]. The flow rate of the oil/water is intended use and functional and the prior art is capable of adjusting the flow rates. Han teaches varying flow rates; [56, 67]); and
a droplet collection module configured to collect the generated droplets (Han teaches the collection module as the outlet; Fig. 8, [52]. See also Figs. 1, 4, 5. The examiner notes that the collection module is just a region of space enabling collection to take place).; wherein the droplets have a diameter equal to or less than 40 um (This limitation is related to intended use and function, and does not further limit the apparatus structure. As best understood, the droplet, mitochondria, and cell are not positively recited, and therefore the limitations do not further limit the apparatus beyond that of a capability. Han teaches that droplets can be generated from several microns to several hundred microns; [44, 45, 92]. The instant application in [33] also states that the droplet size is related to the transfer efficiency where Han is capable of forming various sized droplets; [44, 45, 92].); and wherein an efficiency of mitochondrial transfer is at least 75% (This limitation is related to intended use and function, and does not further limit the apparatus structure. As best understood, the droplet, mitochondria, and cell are not positively recited, and therefore the limitations do not further limit the apparatus beyond that of a capability. The system of Han is capable of using mitochondria and meeting this limitation as Han teaches droplets with particles that can be small molecules and the target particles can be cells; [12, 15]. The instant application states that the transfer efficiency is based on the quality of mitochondria in [3] and Han is capable of using high quality mitochondria. The instant application in [33] also states that the droplet size is related to the transfer efficiency where Han is capable of forming various sized droplets; [44, 45, 92]. The instant application in [35] and Figures 4 also states that the transfer efficiency is based on the number of mitochondria within the droplet, and Han is capable of varying the number of particles/mitochondria in the droplet by varying the concentration and flow rate).
Note: The instant Claims contain a large amount of functional language (ex: “for…”, “configured to…”). However, functional language does not add any further structure to an apparatus beyond a capability. Apparatus claims must distinguish over the prior art in terms of structure rather than function (see MPEP 2114 and 2173.05(g)). Therefore, if the prior art structure is capable of performing the function, then the prior art meets the limitation in the claims.
Han teaches a serpentine structure configured to align molecules into a single streamline (Han; Figs. 1, 5, 8), but Han does not specifically teach a serpentine structure positioned upstream of the flow-focusing structure and configured to align randomly distributed recipient cells into a single-cell streamline. However, Amini teaches a system based on droplet microfluidics (Amini teaches a system for droplet microfluidics; [3], Figs. 1, 3, 5-9) with a droplet generation module with a flow-focusing structure configured to generate the droplet and a serpentine structure positioned upstream of the flow-focusing structure and configured to align randomly distributed recipient cells into a single-cell streamline (Amini teaches the droplet generation module defined by three inlets 302/102, 306/106, 312/112 and their corresponding channels to where the channels meet; Fig. 1, 3, [45]. Amini teaches droplet generation region has a flow focusing structure in the region of 126 that generates the droplets; [45], Fig. 1. See also figures 5-9 which show variations of the device. Amini teaches that channel 108/110 or 308/310 (or channels 104/304, 114/314) can be serpentine with a focusing length which helps to focus/align the components in the channels; [11, 40, 67-69], Figs. 1, 3, 4. See also Figs. 5-9. Amini teaches that channel 304/104 can also be curved; [65-66]. Amini teaches that this helps to achieve the function of 1 cell and 1 bead/particle per droplet; [38, 39, 75,89]). It would have been obvious to one of ordinary skill in the art to have modified the channel(s) upstream of the flow focusing structure of Han to have included serpentine structures as in Amini because Amini teaches that serpentine channels help to focus the components and also decrease the footprint of the device (Amini; [11, 40, 67-69], Figs. 1, 3, 4. See also Figs. 5-9) and because Amini also teaches that the serpentine structure helps to achieve the function of 1 cell and 1 bead/particle per droplet (Amini; [38, 39, 75,89]).
As to claim 2, Han teaches the system according to claim 1 (see above), wherein the droplet generation and observation modules are connected by a conduit (Han teaches that a conduit channel is connecting the modules formed by the junction and the region of space after the junction; Figs. 1, 4, 5, 8).
As to claim 3, Han teaches the system according to claim 1 (see above), wherein the system is disposed on a chip (Han; Figs. 1, 5, 8, [45]).
As to claim 7, Han teaches the system according to claim 1 (see above), wherein the single recipient cell is recipient C2C12 cell (The examiner notes that the single recipient cells are not positively recited as part of the system, and therefore what the cells are defined by is functional/intended use and does not further limit the system structure beyond that of a capability. The system of the prior art is capable of using any cell. Han teaches the mixing of donor particles and target/recipient cells, where the particles can be small molecules and the target particles can be cells; [12, 15]. Han teaches that there are recipient cells through which genetic material is transferred; [74-79, 87]).
As to claim 8, Han teaches the system according to claim 1 (see above), wherein the droplet generation module comprises a flow-focusing structure configured to separate the mitochondrial recipient cell suspension and the isolated mitochondria suspension into droplets (As best understood, Han teaches the flow focusing structure in claim 1 above. Han teaches flow focusing as the region of space at junction where the oil is focused to create droplets; Figs. 1, 5, 8. Han teaches droplet formation; [17]).
As to claim 10, Han teaches the system according to claim 1 (see above), wherein the serpentine structure is configured to improve the ratio of encapsulating the single recipient cell in the droplet more than 47% (The modification of Han to include the serpentine structure of Amini has already been discussed above. Han teaches a channel that is serpentine; Figs. 1, 5, 8. Han also teaches 1 recipient cell in each droplet; [41]. Han also teaches that the number of cells in each droplet is controlled with high accuracy; [44, 56]. Amini teaches that channel 108/110 or 308/310 (or channels 104/304, 114/314) can be serpentine with a focusing length which helps to focus/align the components in the channels; [11, 40, 67-69], Figs. 1, 3, 4. See also Figs. 5-9. Amini teaches that channel 304/104 can also be serpentine; [65-66]. Amini shows in figure 4A the curve that achieves the focusing such that single particles/cells are ordered; Fig. 4. Amini teaches that this helps to achieve the function of 1 cell and 1 bead/particle per droplet; [38, 39, 75,89]. Applicants teach the serpentine structure itself is what focusses the cells to improve single cell encapsulation ratio and suppress the multiple cell encapsulation ratio; see [37] of the instant specification. Therefore, the presence of a wave-like structure that focuses cells is the structure that appears to achieve the claimed function/property, and any serpentine structure that was capable of focusing would be expected to behave the same, and Han teaches the wave-like structure as seen above). When the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, the prior art products necessarily possess the characteristics of the claimed product. See MPEP 2112.01. As stated in In re Best, 562 F.2d 1252, 1255 (CCPA 1977): Where, as here, the claimed and prior art products are identical or substantially identical, or are produced by identical or substantially identical processes, the PTO can require an applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his claimed product. Whether the rejection is based on “inherency” under 35 U.S.C. § 102, on “prima facie obviousness” under 35 U.S.C. § 103, jointly or alternatively, the burden of proof is the same, and its fairness is evidenced by the PTO’s inability to manufacture products or to obtain and compare prior art products. See MPEP 2112.
As to claim 11, Han teaches the system according to claim 1 (see above), wherein the serpentine structure is configured to suppress the ratio of encapsulating multiple recipient cells in the droplet less than 6% (The modification of Han to include the serpentine structure of Amini has already been discussed above. Han teaches a channel that is serpentine; Figs. 1, 5, 8. Han also teaches 1 recipient cell in each droplet; [41]. Han also teaches that the number of cells in each droplet is controlled with high accuracy; [44, 56]. Amini teaches that channel 108/110 or 308/310 (or channels 104/304, 114/314) can be serpentine with a focusing length which helps to focus/align the components in the channels; [11, 40, 67-69], Figs. 1, 3, 4. See also Figs. 5-9. Amini teaches that channel 304/104 can also be serpentine; [65-66]. Amini shows in figure 4A the curve that achieves the focusing such that single particles/cells are ordered; Fig. 4. Amini teaches that this helps to achieve the function of 1 cell and 1 bead/particle per droplet; [38, 39, 75,89]. Applicants teach the serpentine structure itself is what focusses the cells to improve single cell encapsulation ratio and suppress the multiple cell encapsulation ratio; see [37] of the instant specification. Therefore, the presence of a serpentine structure that focuses cells is the structure that appears to achieve the claimed function/property, and any wave-like structure that was capable of focusing would be expected to behave the same, and Han teaches the wave-like structure as seen above). When the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, the prior art products necessarily possess the characteristics of the claimed product. See MPEP 2112.01. As stated in In re Best, 562 F.2d 1252, 1255 (CCPA 1977): Where, as here, the claimed and prior art products are identical or substantially identical, or are produced by identical or substantially identical processes, the PTO can require an applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his claimed product. Whether the rejection is based on “inherency” under 35 U.S.C. § 102, on “prima facie obviousness” under 35 U.S.C. § 103, jointly or alternatively, the burden of proof is the same, and its fairness is evidenced by the PTO’s inability to manufacture products or to obtain and compare prior art products. See MPEP 2112.
As to claim 14, Han teaches the system according to claim 1 (see above), wherein the system is configured to yield at least 2x 106 recipient cells in the droplets for mitochondria transfer in 30 minutes (This limitation is related to intended use and function, and does not further limit the apparatus structure. Additionally, the number of cells created is based on the number of cells used in the input solution, the size of the channels, and the flow rate, all of which the prior art is capable of).
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Han et al (US 20220364120; hereinafter “Han”; already of record) in view of Amini et al (US 20170128940; hereinafter “Amini”; already of record) in view of Microfluidic Chip Shop (Microfluidic Chip Shop, Lab-on-a-chip Catalogue; published 10/2019; hereinafter "Chip Shop"; already of record).
As to claim 4, Han teaches the system according to claim 3, with the chip (see above).
Han does not specifically teach wherein the chip is smaller than 8 cm in length. However, Chip Shop teaches the analogous art of microfluidic chips having various configurations wherein the chip is smaller than 8 cm in length (Chip Shop teaches chips for droplet generation, where the chips are shown to scale and are smaller than 8 cm; p. 73, 76, 77. See also pages 43, 81 where the length is 7.5 cm). It would have been obvious to one of ordinary skill in the art to have modified the microfluidic chip for generating droplets of Han to have been formed on a slide an less than 8 cm in length as in Chip Shop because Chip Shop teaches that microfluidics are known to be made on slides and also at dimensions smaller than 8 cm (Chip Shop; p. 73, 76, 77, 43, 81).
Other References Cited
The prior art of made of record and not relied upon is considered pertinent to applicant's disclosure include;
Shakoor et al (Shakoor et al. Automated Optical Tweezers Manipulation to Transfer Mitochondria from Fetal to Adult MSCs to Improve Antiaging Gene Expressions. Small, vol. 17, published 8/19/21; already of record; hereinafter “Shakoor”) teaches two inlets which make cell drops; Fig. 1. Shakoor teaches the observation module as the region of space in the middle channel with trapped cells for observation; Fig. 1. Shakoor teaches the outlets as the collection module; Fig. 1. Shakoor teaches encapsulating mitochondria in cells.
Kitani et al (Kitani et al, Internalization of isolated functional mitochondira: involvement of micropinocytosis. J. Cell. Mol. Med., vol. 18, no. 8, pp. 1694-1703, 2014; hereinafter “Kitani”; already of record) teaches a that isolated mitochondria can be transferred into cells by co-incubation.
If the mitochondrial recipient cell suspension, molecular complexes, and surfactant-added fluorinated oil were positively recited, then Katrangi et al (Katrangi et al., Xenogenic transfer of isolated murine mitochondria into human p0 cells can improve respiratory function, Rejuvenation Res., vol. 10, no. 4, pp. 561-570, 2007; hereinafter “Katrangi”; already of record) teaches the analogous art of co-culturing cells with isolated mitochondria (Katrangi teaches co-culturing cells with isolated mitochondria, such that the mitochondria in the cells are functional to restore cellular function; p. 561-562, 569-570). It would have been obvious to one of ordinary skill in the art to have modified the particles as molecular complexes that are coupled with cells within the droplet of Amini to have used mitochondira for uptake by the cells as in Katrangi because Katrangi teaches that cells will internalize the mitochondria and therefore restore mitochondrial function to the cell (Katrangi; p. 561-562, 569-570).
If the cells, and specifically the C2C12 cells were positively recited, then Katrangi et al (Katrangi et al., Xenogenic transfer of isolated murine mitochondria into human p0 cells can improve respiratory function, Rejuvenation Res., vol. 10, no. 4, pp. 561-570, 2007; hereinafter “Katrangi”; already of record) teaches that various murine and human cells underwent successful mitochondrial transfer (Katrangi; p. 561-562, 569-570). It would have been obvious to one of ordinary skill in the art to have chosen the cells undergoing mitochondrial transfer in modified Amini to have been C2C12 with a reasonable expectation of success (see KSR rationale E- MPEP 2143) because one of ordinary skill in the art would find it obvious and expect that any cell could be used to investigate mitochondrial transfer Further, it would have been obvious to use the mitochondrial transfer in cells of modified Amini in any cells, including C2C12 cells because the use of a known technique would have predictably resulting in mitochondrial transfer to any cell, including C2C12 cells (see KSR rationale C- MPEP 2143). Additionally, it is known that C2C12 cells, which are muscle cells, require functioning mitochondria in order to properly function, and it would have been obvious to one of ordinary skill in the art to have modified the mitochondrial transfer in cells of modified Amini in C2C12 muscle cells because muscle cells require functioning mitochondria to properly function and produce energy. Alternatively, Sin et al (Sin et al., Mitophagy is required for mitochondrial biogenesis and myogenic differentiation of C2C12 myoblasts. Autophagy, vo. 12, no. 2, pp. 369-380. 2016; hereinafter “Sin”; already of record) Sin teaches the analogous art of the importance of mitochondria to C2C12 cells, and how C2C12 cells are good models for cell differentiation (Sin; p. 377). It would have been obvious to one of ordinary skill in the art to have used the C2C12 cells of Sin as the cells for mitochondrial transfer in cells of modified Amini because Sin teaches the importance of mitochondrial function to C2C12 cells (Sin; p. 377).
Response to Arguments
Applicant’s arguments filed on 12/17/25 have been considered but are moot because the arguments are towards the amended claims and not the current grounds 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.
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/BENJAMIN R WHATLEY/Primary Examiner, Art Unit 1798