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
Applicant’s amendment and remark filed on 08/21/26 have been entered. Claims 1-9 and 11-19 remain pending and examined herein. Applicant’s amendment has overcome each and every rejection under 112(b) set forth in Office Action mailed on 04/21/26.
Status of Rejections
The non-statutory Double patenting rejection of claims 1-9 and 11-19 in view of Pat. No. 12,070,747 B2 is withdrawn by the submission and approval of Terminal Disclaimer.
The 112(b) rejection of claims 16-19 is withdrawn in view of Applicant’s amendment.
The 102(a)(1) rejection of claims 1 and 11 in view of Sawashima (US 20160247697 A1) is maintained.
The 103 rejection of claim 12 in view of Carmona-Fontaine (Metabolic origins of spatial organization in the tumor microenvironment, 2017), Cui (A microfluidic device for isolation and characterization of transcendothelial migrating cancer cells, 2017), and Anderson (US 20110201099 A1) is withdrawn in view of Applicant’s remark and amendment.
The 103 rejection of claim 1-9 and 13-15 in view of Carmona-Fontaine and Cui is maintained.
Terminal Disclaimer
The terminal disclaimer filed on 08/21/26 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of U.S. Patent No. 12,070,747 B2 has been reviewed and is accepted. The terminal disclaimer has been recorded.
Claim(s) 1 and 11 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sawashima (US 20160247697 A1) as cited in previous Office Action.
Regarding claim 1, Sawashima discloses a device (processing unit 2, Fig. 4) comprising:
a chamber (holder 25, Fig. 3-4) having a bottom layer (See Fig. 4, the holder is a square box), two sidewalls (see Fig. 3, the holder is a square box), a first end wall (see Fig. 3, the holder is a square box), a second end wall and a top plate (See the bird-eye view of holder 25 in Figure 4), wherein the bottom layer is connected to the two sidewalls, the first end wall and the second end wall at peripheral edges (the limitation is inherently met as the holder is a square/rectangular box), and wherein the first end wall comprises a plurality of openings (nozzles 26, Fig. 3) positioned between the bottom layer and the top layer (the top of holder 25 and bottom of holder 25 in Fig. 3);
a plurality of ports (main nozzle body 27, Fig. 3, 4, and 6), each port extending outward a length from the first end wall (Fig. 3, 4, and 6), and fluidly connected to an opening of the plurality of openings (the nozzle body is connected to individual tip), wherein the length of each port is different, wherein the length of each port increases incrementally along the first end wall (Fig. 6), wherein each port comprises a needle-access opening aligned with a longitudinal axis of the respective port (If a needle were to be inserted, the needle would have been able to at least aligned with a longitudinal axis of at least part of the respective port).
Claim(s) 1-4, 7, 9, and 13-15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Carmona-Fontaine (Metabolic origins of spatial organization in the tumor microenvironment, 2017) in view of Cui (A microfluidic device for isolation and characterization of transendothelial migrating cancer cells, 2017), as evidenced by Perkin-Elmer (Microplate Dimensions, Working Volumes and Packaging, 2019) as cited in previous Office Action.
Regarding claim 1, Carmona-Fontaine discloses a discrete microenvironment chamber (DIMIC) device (metabolite microenvironment chamber (MEMIC)) (Gradients of Oxygen and Lactate Orchestrate Spatial Patterns of Cell Phenotypes) (Figure 2A) comprising:
a chamber (a small chamber) (Figure 2 Description, Page 2936) having a bottom layer (See annotated figure below), two sidewalls (see annotated figure below), a first end wall (see annotated figure below), a second end wall and a top plate (cover) (Figure 2), wherein the bottom layer is connected to the two sidewalls, the first end wall and the second end wall at peripheral edges (The bottom layer appears to be connected to the two side walls and end walls in the annotated figure).
Carmona-Fontaine does not disclose at least one opening positioned between the bottom layer and the top plate; and at least one port extending outward from the first end wall, wherein the at least one port is fluidly connected to the at least one opening.
In an analogous art, Cui discloses a microfluidic device for cultivating and transporting cancer cells. The device comprises a cell collection microchamber/layer comprising cell extraction microchannels located on an end wall of the microfluidic device (Figure 1a). To avoid unwanted interference, the microchannels were situated at the corner of each compartment/microchamber. It would have been obvious to one of skill in the art before the effective filing date to incorporate the cell extraction channels/ports from Cui to the end walls, which are connected to the bottom layer, of Carmona-Fontaine’s microchamber to derive the claimed device. Doing so allows one to selectively collect/extract cells from different compartment/chamber of the microfluidic device (Abstract, Cui).
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Neither Carmona-Fontaine nor Cui nor combination of both explicitly discloses plurality of ports each have different lengths.
Regarding the limitation of the plurality of ports each have different lengths, Carmona-Fontaine already discloses the concentration gradients of the cell media/samples vary depending on the position (…experiments suggest that extracellular metabolite gradients play a key role in the phenotypic diversity of TAMs) (Gradients of Oxygen and Lactate Orchestrate Spatial Patterns of Cell Phenotypes, pg 2935, right column). Furthermore, Carmona-Fontaine suggest that the concentrations of oxygen and lactate (nutrient and waste products) are not uniform in the cell media; thus, the concentrations of nutrients and waste products vary depending on the positions (Altogether our data show that, by sensing lactate and oxygen levels, TAM scan determine their position with respect to the vasculature (or to the slit in the MEMIC)) (Positional information is interpreted via MAPK/ERK Signaling, Pg. 2937). The positional information is used to determine the location of fastest-growing tumors (Positional Information Optimizes Angiogensis and Leads to Faster-Growing Tumors, Pg. 2937-2938) (See Figure 1C, 2DEG, 3C, and 4ADH). Based on the results supplied by Carmona-Fontaine, one of ordinary skill in the art would have recognized the need to sample the cultured media at different location/position (interpreted as claimed local environment) since the concentrations would have been different. Therefore, it would have been obvious to one of ordinary skill in the art to further modified Carmona-Fontaine in view of Cui by duplicating Cui’s extraction channels and varying the penetration depth/length of each channel. Doing so allows one to sample the cell culture at different depth/distance and measure the concentration(s) of lactate and/or oxygen at the specific position. The information gathered allows one to determine the region of fastest-growing tumor (Carmona-Fontaine; Positional Information Optimizes Angiogensis and Leads to Faster-Growing Tumors, Pg. 2937-2938). Furthermore, Cui, after incorporation, would have disclosed the an opening wherein the opening aligned with a longitudinal axis of the respective port.
Regarding claims 2 and 3, Modified Carmona-Fontaine discloses the invention as discussed above in claim 1. Carmona-Fontaine does not disclose the explicit dimension of the distance between the sidewalls and end walls. Carmona-Fontaine discloses the device was designed to have the same size as microtiter plates, which allowed it to be mounted on conventional microscope stages (Supplement, Fabrication of MEMIC). Commercial microplate has length 128 mm x the width 86 mm, which would anticipate the disclosed range by Carmona-Fontaine. See Perkin-Elmer for example.
Regarding claim 4, Modified Carmona-Fontaine discloses the invention as discussed above in claim 1. Carmona-Fontaine discloses that the top plate is positioned parallel and above the bottom layer (See annotated figure above, top cover is parallel to the bottom layer), connected to the two side walls and the first end wall and creates an opening with respect to the second end wall and a small gap between the top plate and the bottom layer (see annotated figure above).
Regarding claim 7, Modified Carmona-Fontaine discloses the invention as discussed above in claim 1. Cui disclosed that there are at least two openings/microchannels for every compartment, one for extraction, one for injection (Figure 1a). Neither Carmona-Fontaine nor Cui discloses the openings distance between the at least two openings ranges approximately between about 0.05-10 mm. As discussed in MPEP 2144.04(IV)(A), where the only difference between the prior art and the claims is a recitation of relative dimensions of the claimed device and a device having the claimed relative dimensions would not perform differently than the prior art device, then the claimed device is not patentably distinct from the prior art device. See Gardner v. TEC Syst., Inc., 725 F.2d 1338, 220 USPQ 777 (Fed. Cir. 1984), cert. denied, 469 U.S. 830, 225 USPQ 232 (1984). Furthermore, as disclosed by Carmona-Fontaine, the sample size of cell culture/tumor ranges from 50-4000 micrometers (0.05-4 mm), so it would have been obvious to one of ordinary skill in the art to modify the device dimension and derive the claimed dimension based on the cell culture sample size/diameter through routine experimentation. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In reAller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). A mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.”). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416, 82 USPQ2d 1385, 1395 (2007) (identifying “the need for caution in granting a patent based on the combination of elements found in the prior art.”).
Regarding claim 9 specifically, Modified Carmona-Fontaine discloses the claimed invention as discussed above in claim 1. Though neither Carmona-Fontaine nor Cui explicitly discloses the claimed dimension, Carmona-Fontaine does disclose that the device should be size of standard/conventional microtiter plates (The MEMIC was designed to have the same size as microtiter plates) (Supporting Information, Fabrication of MEMIC). Commercial microplate has length 128 mm x the width 86 mm (See Perkin-Elmer). As discussed in MPEP 2144.04(IV)(A), where the only difference between the prior art and the claims is a recitation of relative dimensions of the claimed device and a device having the claimed relative dimensions would not perform differently than the prior art device, then the claimed device is not patentably distinct from the prior art device. See Gardner v. TEC Syst., Inc., 725 F.2d 1338, 220 USPQ 777 (Fed. Cir. 1984), cert. denied, 469 U.S. 830, 225 USPQ 232 (1984). Furthermore, Carmona-Fontaine already discloses that the device should be able to accommodate commercial microplate. it would have been obvious to one of ordinary skill in the art to modify the device dimension and derive the claimed dimension based on the length of the injection/extraction device through routine experimentation. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In reAller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). A mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.”). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416, 82 USPQ2d 1385, 1395 (2007) (identifying “the need for caution in granting a patent based on the combination of elements found in the prior art.”).
Regarding claim 13-15, Modified Carmona-Fontaine discloses the claimed invention as discussed above in claim 1. Carmona-Fontaine discloses a cell tray that covers portions of the bottom layer or completely. See annotated figure below.
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Claim 5-6 and 8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Carmona-Fontaine in view of Cui as discussed above in claim 4, and further in view of Bucci (Emergence of spatial structure in the tumor microenvironment due to the Warburg effect, 2015).
Regarding claims 5, 6, and 8, Modified Carmona-Fontaine discloses the claimed invention as discussed above in claim 4. (Claims 5 and 6) and claim 1 (Claim 8) respectively. Neither Carmona-Fontaine nor Cui discloses the specific dimensions claimed. The combination of Carmona-Fontaine and Cui teaches all the recited features in claim 4. As discussed in MPEP 2144.04(IV)(A), where the only difference between the prior art and the claims is a recitation of relative dimensions of the claimed device and a device having the claimed relative dimensions would not perform differently than the prior art device, then the claimed device is not patentably distinct from the prior art device. See Gardner v. TEC Syst., Inc., 725 F.2d 1338, 220 USPQ 777 (Fed. Cir. 1984), cert. denied, 469 U.S. 830, 225 USPQ 232 (1984). Furthermore, in another study done by Carmona-Fontaine (hereinafter Bucci), it was disclosed that a microenvironment chamber is used to study the culturing of cancer cells . The microenvironment chamber has opening of 10 mm and height of 0.73 mm (Figure 3A). It would have been obvious to one of ordinary skill in the art to modify the device dimension of Carmona-Fontaine based on that of Bucci (using opening of 10 mm and height of 0.73 mm). It would have been obvious to one of skill in the art to use the dimensions recited in Bucci to modify the device in Carmona-Fontaine. One has a motivation to do so because both arts disclose studying of culturing of cancer using microenvironment chamber with similar structure (See 2A” of Carmona-Fontaine and 3A of Bucci). Furthermore, both arts were done by Carmona-Fontaine, wherein the primary art (i.e. Carmona-Fontaine) is an extension (newer) to Bucci’s disclosure.
Allowable Subject Matter
Claims 12 and 16-19 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter:
Claims 16 is indicated allowable for reciting substantially identical subject matter as claim 1 of U.S. Pat. No. 12,070,747 B2, which is previously allowed.
Claims 17-19 are also allowable for being dependent on claim 16.
Regarding claim 12, Applicant’s arguments, see Pages 7-8, filed 08/21/26, with respect to claim(s) 12, have been fully considered and are persuasive. The rejection of claim 12 has been withdrawn.
In consideration based on prior art combination Carmona-Fontaine, Cui, and Anderson:
Specifically, Cui, after incorporation, discloses the extraction channel/port is controlled by microvalves. As such there is no sufficient reason or advantage disclosed by Anderson for substituting microvalves with syringe needle with a reasonable expectation of success. Furthermore, even if substitution is deemed successful, the combination fails to disclose an embodiment wherein the needles having a first end positioned within the chamber, a second positioned outside the chamber and a lumen therebetween.
In consideration based on prior art Sawashima:
Specifically, the ports in Swashima are angled as shown below. As such, even if it were possible to insert needles via the nozzles 26, the needle would not be able to reach chamber 25 as shown in Fig. 3. Hence, One of ordinary skill in the art would not have been able to teach an embodiment wherein the needles having a first end positioned within the chamber, a second positioned outside the chamber and a lumen therebetween as the needle would not be able to reach the chamber due to the bend in the ports
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Response to Arguments
Applicant's arguments filed 08/21/26 have been fully considered but they are not persuasive.
The remarks were directed to newly amended matter needle-access opening aligned with a longitudinal axis of the respective port (See pages 6-9). Examiner respectfully disagreed.
MPEP 2114 states ‘“[A]pparatus claims cover what a device is, not what a device does.” Hewlett-Packard Co.v.Bausch & Lomb Inc., 909 F.2d 1464, 1469, 15 USPQ2d 1525, 1528 (Fed. Cir. 1990) (emphasis in original). 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.’
First, almost any nozzle or hole could be qualified “as needle-access opening” as needle were known to have a small diameter. As such the amendment itself does not meaningfully limit the claim with this limitation as almost any nozzle or hole can accommodate a needle even if that is not the intended use of the nozzle. Furthermore, the claim recites “a longitudinal axis”. The article “a” suggests that a port may have multiple longitudinal axis. As such both Sawashima and Cui, after incorporation into Carmona-Fontaine, would still teach this limitation.
Specifically, for Sawashima, as shown in Fig. 3 above, if a needle were to be inserted into nozzle 29, the needle would at least be in alignment with longitudinal axis of part of the port (the part of the port extending from nozzle to the beginning of the angled portion). As such, Sawashima would still have taught this limitation as well.
However, upon further consideration of Applicant’s remark with respect to claim 12, the rejection of claim 12 in view of Carmona-Fontaine, Cui, and Anderson is withdrawn (Page 8-9 of the remark) as the claim explicitly requires a needle to be inserted into the chamber in a very specific orientation. See allowable subject matter section above.
For the reasons above, the rejection of claims 1-9, 11, 13-15 is maintained.
Applicant’s arguments, see Pages 7-8, filed 08/21/26, with respect to claim 12 have been fully considered and are persuasive. The rejection of claim 12 has been withdrawn.
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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/M.H./Examiner, Art Unit 1758
/MARIS R KESSEL/Supervisory Patent Examiner, Art Unit 1758
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