DETAILED 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 .
Response to Amendment
The Amendment filed 03/18/2026 has been entered. Claims 1-24, 26 and 28-29 are pending in the application. Claims 15-24 and 26 are withdrawn. Claims 1-14 and 28-29 are being examined herein.
Status of Objections and Rejections
The rejections of claims 2 and 3 under 35 U.S.C. 112(b) relating to “the first circular cell traps” are maintained. The remaining rejections under 35 U.S.C. 112(b) are being withdrawn in view of Applicant’s amendment.
New grounds for rejection under 35 U.S.C. 112(b) are necessitated by Applicant’s amendments.
The rejections under 35 U.S.C. 102 and 35 U.S.C. 103 are withdrawn in view of Applicant's amendment.
New grounds of rejection under 35 U.S.C. 102 and 35 U.S.C. 103 are necessitated by the amendments
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 1-14 and 28-29 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.
Claim 1 is amended to recite the limitation " wherein the cell traps within each of the one or more concentric circular arrays are positioned with a spacing relative to one another that minimizes clogging and maximizes capture of the cells of the population " in lines 8-10. It is unclear what is required structurally (e.g., dimension, placement) for the spacing to minimize clogging and maximizes capture of the cells of the population. Furthermore, it unclear how “minimizes clogging” and “maximizes capture of cells” is determined and defined (is it through experimentation? What are the thresholds for clogging and capturing of cells to be considered minimized and maximized, respectfully). Therefore, this limitation does not clearly set forth the metes and bounds of the patent protection desired. Clarification is requested.
Claims 2-14 and 28-29 are indefinite because of their dependency on claim 1.
Claims 2 and 3, as states in the previous office action, each recites the limitation “the first circular array of cell traps” in line 2. There is insufficient antecedent basis for this limitation in the claim. It is unclear, which circular array is the first circular array. It is unclear whether it is referring to (1) one of the “one or more concentric circular arrays” in claim 1, or (2) one of the circular arrays within one of the “one or more circular arrays.” The examiner notes that a concentric circular array has more than one circular arrays. Furthermore, it is also unclear which one is “the first.” Clarification is requested. For the purpose of examination, the limitation is being interpreted as “the first circular array of cell traps from the center”, and it is part one of the circular array arrays within one of the “one or more concentric circular arrays.
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.
Claim 1, 7-8, 10-11, 13-14 and 28-29 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Qin et al. (US 20170209863 A1).
Regarding claim 1, Qin teaches a microfluidic system for cell pairing and cell fusion (Fig. 1), comprising
i) a transparent layer (microfluidic aliquot MA chip) in a disc shape (para. 0080, round PDMS MA chip) ; and
ii) a support layer (petri dish)(para. 0080),
wherein the transparent layer comprises a plurality of cell traps (side wells 114)(Fig. 1 and para. 0064) and at least one central inlet port (center well 110)(abstract and Fig. 1) for receiving a sample of liquid and a population of cells in the cell traps (abstract and Fig. 1);
wherein the cell traps (114) are arranged in one r1 and r2)(Fig. 1C; the strike-through part is optional because of the “or”) around the at least one central inlet port (110) forming a ring of a circular cell trap zone (Fig. 1);
wherein the cell traps within each of the one or more concentric circular arrays are positioned with a spacing (the spacing between cell traps)(Fig. 1C) relative to one another that minimizes clogging and maximizes capture of the cells of the population (the cells are not positively recited. The spacing of the Qin’s device does not cause clogging and able to capture cells, and thus meet this limitation. See also the 35 U.S.C. 112(b) section above); and
wherein the circular cell trap zone has a thickness that is greater than the population of cells largest cell size contained therein (para. 0061 and Fig. 1A thickness of the chip is ~1 mm, which greater than any typical cells).
Regarding claim 7, Qin teaches all of the elements of the current invention as stated above with respect to claim 1. Qin further teaches wherein the transparent layer (MA chip) has a diameter between about 2 cm and about 20 cm, inclusive (para. 0068, the MA chip 100 has radius of 3 cm, which is 6 cm in diameter).
Regarding claim 8, Qin teaches all of the elements of the current invention as stated above with respect to claim 1. Qin further teaches wherein the ring of the circular cell trap zone (annular outer portion, which is between r3 to r. Fig. 1C and para. 0069)has an inner diameter (radius r3 multiplied by 2) between about 1 cm and about 4, inclusive cm (Fig. 1C and para. 0069, r3 is at least 50% of radius of MA chip, and thus r3 is at least 1.5 cm. Therefore, the inner diameter is at least 3 cm, which is within 1 cm to about 4 cm), and an outer diameter (radius of the MA chip multiplied by 2) between about 2 cm and about 10 cm, inclusive (the radius of MA chip r is 3 cm, and thus diameter is 6 cm, which is within the range of 2 and 10 cm ).
Regarding claim 10, Qin teaches all of the elements of the current invention as stated above with respect to claim 1. Qin further teaches wherein the transparent layer and the cell traps are made from polydimethylsiloxane (para. 0061, MA chip is made of polydimethylsiloxane PDMS).
Regarding claim 11, Qin teaches all of the elements of the current invention as stated above with respect to claim 1. Qin further teaches, wherein the support layer is made from glass or plastic (petri dish is made of glass or plastic), optionally with electrodes (“optionally” indicates not required, and thus does not further limit the structure of the invention).
Regarding claim 13, Qin teaches all of the elements of the current invention as stated above with respect to claim 1. Qin further teaches wherein the inlet port is connected to a robotic pipetting system for receiving the sample of liquid and the population of cells (interpreted as an intended use. A robotic pipetting system is not positively recited. The inlet port meets the structural limitation of the intended use).
Regarding claim 14, Qin teaches all of the elements of the current invention as stated above with respect to claim 1. Qin teaches wherein the inlet port is connected to a rotary union for receiving the sample of liquid and the population of cells and removing the cells and reagents passing through the chip (interpreted as an intended use. A rotary union is not positively recited. The inlet port meets the structural limitation of the intended use).
Regarding claim 28, Qin teaches all of the elements of the current invention as stated above with respect to claim 1. Qin further teaches wherein the spacing is a horizontal spacing between cell traps within each of the concentric circular arrays (para. 0064, Figs. 1A and -1C, the cell traps are horizontal to one another, and thus the spacing is also horizontal).
Regarding claim 29, Qin teaches all of the elements of the current invention as stated above with respect to claim 1. wherein the spacing is a vertical spacing between concentric circular arrays that are parallel to one another (the invention is being interpreted with the alternative of one concentric circular array. This limitation requires more than one concentric circular arrays, and thus does not apply).
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.
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.
Claims 2 and 3 are rejected under 35 U.S.C. 103 as being unpatentable over Qin et al. (US 20170209863 A1) in view of Lee et al. (US 20200238288 A1)
Regarding claim 2, Qin teaches all of the elements of the current invention as stated above with respect to claim 1. Qin teaches a microfluidic chip for capturing/trapping of single cells (Abstract). Qin teaches the chip is useful for capturing circulating tumor cancer (CTC) cells from blood (Abstract) for further analysis. Qin teaches the chip is a PDMS disc, comprises a inlet port (110) at the center, wherein the inlet port is connected to two circular arrays of cell traps 114 through the corresponding channels 112 (Fig. 1, 1A and 1B).
Qin does not teach wherein the area between the central inlet port and the first circular array of cell traps (cell traps residing at radius r1)(See the 35 U.S.C. 112(b) section above) comprises a plurality of support pillars.
However, Lee teaches a microfluidic device for single-cell trapping for capturing CTC from blood samples. Lee further teaches the device is fabricated in PDMS (par. 0138) and comprises an inlet, an inlet channels and a trapping region (Fig. 1A and para. 0150). Lee further teaches the inlet channels comprises pillar structures that function as pre-filters to prevent the introduction of cancer cell aggregates into the trapping region (para. 0150).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the inlet channels taught by Qin to include pillar structures taught by Lee in order to prevent introduction of cancer cell aggregates into the cell traps with a reasonable expectation of success (Lee, para. 0015) (MPEP 2143)(I)(G).
The teachings of Qin as modified by Lee would yield wherein the area between the inlet port (110) and the first circular array of cell traps (cell traps residing at r1)(Fig. 1C) comprises a plurality of support pillars (pillar structures taught by Lee)(Fig. 1, channel 114 are in the area between the inlet port 110 and the cell traps).
Regarding claim 3, Qin teaches all of the elements of the current invention as stated above with respect to claim 1. Qin teaches a microfluidic chip for capturing/trapping of single cells (Abstract). Qin teaches the chip is useful for capturing circulating tumor cancer (CTC) cells from blood (Abstract) for further analysis. Qin teaches the chip is a PDMS disc, comprises a inlet port (110) at the center, wherein the inlet port is connected to two circular arrays of cell traps 114 through the corresponding channels 112 (Fig. 1, 1A and 1B).
Qin does not wherein the area between the inlet port and the first circular array of cell traps (cell traps residing at radius r1)(See the 35 U.S.C. 112(b) section above) comprises a plurality of cell filters.
However, Lee teaches a microfluidic device for single-cell trapping for capturing CTC from blood samples. Lee further teaches the device is fabricated in PDMS (par. 0138) and comprises an inlet, an inlet channels and a trapping region (Fig. 1A and para. 0150). Lee further teaches the inlet channels comprises pillar structures that function as pre-filters to prevent the introduction of cancer cell aggregates into the trapping region (para. 0150).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the inlet channels taught by Qin to include pillar structures taught by Lee in order to prevent introduction of cancer cell aggregates into the cell traps with a reasonable expectation of success (Lee, para. 0015) (MPEP 2143)(I)(G).
The teachings of Qin as modified by Lee would yield wherein the area between the inlet port (110) and the first circular array of cell traps (cell traps residing at r1)(Fig. 1C) comprises a plurality of cell filters (pillar structures taught by Lee)(Lee, para. 0150, the pillar structures are used as filters), preferably arranged in one or more concentric circular arrays around the central inlet port (interpreted as merely exemplary and thus not required. See 35 U.S.C. 112(b)).
Claims 4-6 are rejected under 35 U.S.C. 103 as being unpatentable over Qin et al. (US 20170209863 A1) in view of Dura (“Deformability-based microfluidic cell pairing and fusion.” Lab Chip, 2014,14, 2783-2790)(provided by Applicant’s IDS of 06/25/2024).
Regarding claim 4, Qin teaches all of the elements of the current invention as stated above with respect to claim 1. Qin teaches, wherein the cell trap comprises a single-cell capture cup with a constriction (the opening between side well 114 and channel 112).
Qin teaches a microfluidic chip for single-cell capture. Qin teaches the chip is a PDMS disc, comprises a inlet port at the center, wherein the inlet port is connected to cell traps 114 through the corresponding channels 112 (Fig. 1, 1A and 1B). Qin teaches the chip captures and isolates single cells in a damage-free way and the captured cell can further be proliferate to form cloning within the side wells (cell traps) or retrieved for further analysis (para. 0029). Qin further teaches the device is useful for research areas including clonal mutation, tumor evolution, embryonic development, and immunological intervention (para. 0003).
Qin fails to teach the cell trap comprises a double-cell capture cup, and one or more support pillars in contact with the support layer.
However, Dura teaches a microfluidic PDMS device for sequential single-cell trapping to perform cell pairing and fusion. Dura teaches the cell trapping structure consists of a single-cell trap connected to a double-cell trap through a constriction (Fig. 1c, d). Dura further teaches support pillars are placed on each side of the traps along with openings in the middle of each sidewall provide fluid flow through the cups to direct cells into traps (p. 2784, left column). Dura further teaches the single-cell trap was tailored smaller than cell diameter to ensure capture of only one cell (p. 2784, left column). Dura further teaches that cell fusion is related to the field of embryogenesis, development and immune responses, and has further been implicated in the progression of cancer and immunotherapy (p. 2783, Introduction).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the side wells (cell traps) in the chip taught by Qin with cell trap comprises a single-cell capture cup with a constriction, a double-cell capture cup, and one or more support pillars in contact with the support layer, wherein the constriction is similar or smaller than the diameter of a single cell taught by Dura in order to perform cell pairing and fusion for research in cancer progression and immunotherapy with a reasonable expectation of success (Dura, introduction) (MPEP 2143)(I)(G).
Regarding claim 5, modified Qin teaches all of the elements of the current invention as stated above with respect to claim 4. Modified Qin further teaches wherein the opening of the constriction is similar or smaller than the diameter of a single cell (Dura, p. 2784, left col., also see claim 4) to ensure capture of only one cell (interpreted as an intended use. Moreover, modified Qin teaches this limitation as discussed in Dura, p. 2784, left column).
Regarding claim 6, modified Qin teaches all of the elements of the current invention as stated above with respect to claim 4, wherein the support pillars are placed on both sides of the trap (Dura, p. 2784, left col.) to increase the fractional flow rate through the traps (interpreted as an intended use. Moreover, modified Qin teaches this limitation as discussed in Dura, p. 2784, left column).
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Qin et al. (US 20170209863 A1) in view of Lichtenstein et al. (US 20220055031 A1).
Regarding claim 9, Qin teaches all of the elements of the current invention as stated above with respect to claim 1.
Qin teaches a microfluidic chip for capturing/trapping of single cells (Abstract). Qin teaches the chip can be used capturing circulating tumor cells from blood for further analysis (Abstract).
Qin teaches the chip has a total of 120 cell traps, and thus fails to teaches the system has a total number of cell traps between about 100,000 and 1,000,000, inclusive.
However, Lichtenstein teaches a system for capturing cells from biological fluid for analysis (para. 001). Lichtenstein further teaches system comprises a pluralities of cell extraction modules (cell traps) arranged in a single layer array, and each extraction module is configured to receive and retain a single target cell from a fluid sample (Abstract). Lichtenstein teaches the systems comprises at least of 100,000, 500,000 or 1 million cell extraction modules (para. 0020) to enable high throughput pharmaceutical testing (para. 0172).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the chip taught by Qin to have a total number of cell traps between about 100,000 and 1,000,000 as taught by Lichtenstein in order to enable high-through pharmaceutical testing with a reasonable expectation of success. (Lichtenstein, para. 0172) (MPEP 2143)(I)(G).
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Qin et al. (US 20170209863 A1) in view of Gülzow et al. (US20110003376).
Regarding claim 12, Qin teaches all of the elements of the current invention as stated above with respect to claim 1.
Qin teaches a microfluidic chip for single-cell capture. Qin teaches the chip is a PDMS disc, comprises a inlet port at the center, wherein the inlet port is connected to cell traps 114 through the corresponding channels 112 (Fig. 1, 1A and 1B). Qin teaches the chip captures and isolates single cells in a damage-free way and the captured cell can further be proliferate/culture to form cloning within the side wells (cell traps).
Qin teaches that the PDMS is directly place in a Petri dish (support layer) but fails to explicitly teach wherein the microfluidic system further comprises a plastic cover attached to the support layer to create a reservoir for collection of cells and reagents passing through the chip.
However, Gülzow (US20110003376) teaches a cell culture dish (1) for cultivating/proliferating cells (Abstract and para. 0004). Gülzow teaches cell culture dish comprises (1) a dish (2) and a lid (3), which sits sealingly on the side wall of the dish in aeration position during cell culture (para. 0014). Gülzow teaches the culture dish is made of plastic (para. 0026). Gülzow further teaches of the dish is user friendly where the lid can be put on the dish in arbitrary positions, and the user needs only one single hand for doing this (para. 0014).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the support layer (Petri dish) taught Qin with the Petri dish comprising dish 2 and lid 3 taught by Gülzow in order to order to culture cells with a user-friendly culture dish with a reasonable expectation of success (Gülzow, para. 0014) (MPEP 2143)(I)(G).
The teachings of Qin as modified by Gülzow would yield wherein the microfluidic system further comprises a plastic cover (lid 3 of Gülzow, which is made of plastic) attached to the support layer (dish 2) to create a reservoir (dish 2 and lid 3 is a reservoir) for collection of cells and reagents passing through the chip (interpreted as an intended use. Reservoir, cells and reagents are not positively recited. Dish 2 and lid 3 meets the structurally limitation of the intended use).
Response to Arguments
Applicant’s arguments, see pp. 7-8, filed 03/18/2026, with respect to the rejections under 35 U.S.C. 112(b) have been fully considered. The amendment has addressed the issues relating the broad ranges with narrow ranges. However, the amendment does not address the antecedent basis issues for claim 2 and 3 (see p. 4 of OA mailed 11/18/2025). Therefore, the rejections of claim 7 and 9 has been withdrawn, and the rejections of claim 2 and 3 are maintained.
Applicant’s arguments, see 8-11, filed 03/18/2026, with respect to the rejections under 35 U.S.C. 102 have been fully considered and are not persuasive.
The Applicant argues that claim 1 and its dependent claims are novel over Qin. In particular, the Applicant argues that Qin does not disclose the newly added limitations of claim 1, “wherein the cell traps within each of the one or more concentric circular arrays are positioned with a spacing relative to one another that minimizes clogging and maximizes capture of the cells of the population” and “wherein the circular cell trap zone has a thickness that is greater than the population of cells largest cell size contained therein.” The Applicant explains that the instant invention allows for fluids to be able to flow both into and around the cell traps to allow for the cells therein to be captured by the cell traps, with “no channels … directly connect the central inlet port and the cell traps”, and consequently a spacing between the cell traps is selected to “that minimizes clogging and maximizes capture of the cells of the population. The Applicant argues that Qin provide no disclosure relevant to the spacing because “Qin explicitly relies on direct flow from a center well to side wells via individual connecting channels and there is no flow around the side wells.” In addition, the Applicant further argues “Qin also provides no disclosure relevant to selecting a thickness of a circular cell trap zone based on the largest cell size in a population,” which is required by the amended claim 1.
The examiner respectfully disagreed. It first noted that the limitation “wherein the cell traps within each of the one or more concentric circular arrays are positioned with a spacing relative to one another that minimizes clogging and maximizes capture of the cells of the population” does not provide necessary details for one to ascertain what is required of the spacing (e.g., dimension, placement) to “minimizes clogging and maximizes capture of the cells of the population.” In addition, it is unclear how ”minimizes clogging” and “maximizes capture of cells” are defined and determined. Is it through experimentation? What are thresholds of degrees of clogging and capturing of cells that the spacing need to achieve to be considered the clogging and capturing cells are minimized and maximized, respectively? Therefore, the limitation does not clearly set forth the metes and bounds of the patent protection desired. For this reason, this limitation is indefinite as indicated in the 35 U.S.C. 112(b) above. Since Qin teaches a spacing between the side wells (cell traps), and with the spacing, there are no reported clogging issues, and the spacing also allow for capturing cells, and thus Qin teaches this limitation under the broadest reasonable interpretation.
With regard to the limitation “wherein the circular cell trap zone has a thickness that is greater than the population of cells largest cell size contained therein, Qin teaches the thickness of the chip which is also the thickness of the cell traps is ~1 mm (para. 0061 and Fig. 1A). Since ~1 mm is greater any typical cells, and thus Qin teaches this limitation.
In addition, the examiner notes that the limitation relating to a spacing in claim 1 does not require the prior art to teach flow both into and around the cell traps, or with no channels directly connecting the central inlet port and the cell traps. 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). Furthermore, "a claim containing a 'recitation with respect to the manner in which a claimed apparatus is intended to be employed does not differentiate the claimed apparatus from a prior art apparatus' if the prior art apparatus teaches all the structural limitations of the claim" (MPEP 2114 II).
Therefore this argument is unpersuasive.
Applicant’s arguments, see pp. 11-13, filed 03/18/2026, with respect to the rejections under 35 U.S.C. 103 have been fully considered and are not persuasive.
The Applicant argues that the dependent claims 2-3, 4-6, 9 and 12 are not obvious over Qin in view Lee et al. (US 20200238288 A1), Dura (“Deformability-based microfluidic cell pairing and fusion.” Lab Chip, 2014,14, 2783-2790), Lichtenstein (US 20220055031 A1), or Gülzow (US20110003376) for the reason that the above references do not cure the alleged deficiencies found in Qin’s teachings of claim 1. However, the argument does not provide any specific supposed errors in the examiner’s action, and as discussed above, the teachings of Qin teaches every limitation of claim 1, and thus have no deficiencies. Therefore, this argument is unpersuasive.
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.
/M.L.C./ Examiner, Art Unit 1758
/REBECCA M FRITCHMAN/ Primary Examiner, Art Unit 1758
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