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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1 – 15 in the reply filed on 18 March 2026 is acknowledged.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 02 January 2024 was filed. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 103
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 (i.e., changing from AIA to pre-AIA ) 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 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 1 – 3, 5, 6, and 8 – 15 are rejected under 35 U.S.C. 103 as being unpatentable over Veres et al (US 20200377838 A1) in view of Lee (US 20230147702 A1) and further in view of Petropolis et al (US 20220106547 A1).
With regards to claim 1, Veres et al teaches;
The claimed layer “comprising a plurality of microfluidic channels each having an inlet and an outlet” has been read on the taught ([0057], “Each of the flanking channels 16a,b and the CR 12 has a respective set of two fluid ports 17 (inlets/outlets).”);
The claimed “a matrix channel comprising a diffusion barrier having pores” has been read on the taught ([0053], “The microfluidic device includes a microfluidic chamber with at least one fluid-permeable fencing that divides the chamber into at least 3 volumes. At least one of these volumes contains a porous bed of […] rigid particles (beads).”; [0056], “A central region 12 of the chamber 11…”; Figure 1 shows the central region containing beads.”);
The claimed “a donor cell channel structured to receive a donor cell population” and “a recipient cell channel structured to receive at least a recipient cell population” has been read on the taught ([0057], “The fencing 14 separates the chamber 11 into two flanking channels 16a,b…”; [0083], “Cells 50a,b are grown on each side of the bead bed defining respective biowalls.”);
The claimed “the diffusion barrier being structured to mimic extracellular matrix and conduit a target subject from the donor cell channel to the recipient cell channel through the pores” has been read on the taught ([0073], “…a bead bed (a packing mostly consisting of rigid powders…)”; [0073], “The powder is divided into at least two segments, and each of the segments (or any mixture of the segments of different powders) is independently treated with, for example, by surface deposition of proteins, polymers, and other biochemical or organic products… For example, […] extra-cellular matrix (ECM)…”);
The claimed “wherein upon injection of the donor cell population and the recipient cell population respective cell channels, the target subject is imaged by an imaging device couplable to the microfluidic intercellular communication analysis device and analyzed for intercellular communication thereof, and/or functional characterizations for ensuing intercellular communication effects” has been read on the taught ([0089], “FIG. 6B shows the imaging system with the chip and fluid supply system…”).
The limitations of “a donor cell population,” and “a recipient cell population” describe the material worked upon by the device, and do not provide further patentable weight to the claims as the device of Veres et al is capable of supporting cell populations; please see MPEP 2115.
The limitation of “wherein upon injection of the donor cell population and the recipient cell population respective cell channels, the target subject is imaged by an imaging device couplable to the microfluidic intercellular communication analysis device and analyzed for intercellular communication thereof, and/or functional characterizations for ensuing intercellular communication effects” is functional language describing the intended use of the device and has been given the appropriate patentable weight. Please see MPEP 2114(II), and Hewlett-Packard Co. v. Bausch & Lomb Inc., 909 F.2d 1464, 1469, 15 USPQ2d 1525, 1528 (Fed. Cir. 1990). As Veres et al teaches all of the structural limitations of the apparatus as defined in claim 1, this additional limitation does not define the instant application over the prior art.
However, Veres et al does not explicitly disclose a coverslip, and a Polydimethylsiloxane (PDMS) layer attached to upper surface of the coverslip, or the donor cell channel and the recipient cell channel each comprising inlets and outlets having an arc angle ranging from 180 degrees to 300 degrees, the arc angle being structured to prevent cell aggregation in the inlets, the outlets and/or channel surfaces of the donor cell channel and the recipient cell channel
In the analogous art of microfluidic cell culture devices, Lee teaches;
The claimed “a coverslip, and a Polydimethylsiloxane (PDMS) layer attached to upper surface of the coverslip” has been read on the taught ([0141], “The PDMS replica was then bonded to precleaned microscope glass slides…”; The PDMS replica of a microfluidic chip reads on a PDMS layer. The microscope glass slides reads on the upper surface of a coverslip.);
The claimed “the PDMS layer comprising a plurality of microfluidic channels each having an inlet and an outlet” has been read on the taught ([0003], “The present disclosure relates to an in vitro microphysiological system comprising a plurality of microfluidic channels…”; [0031], “A channel typically comprises an inlet through which a volume of liquid can be injected. Channels optionally also comprise outlets or vents…”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the device including a microfluidic chip with the PDMS layer and a coverslip as taught by Lee et al. According to MPEP 2143(I)(C), use of a known technique to improve similar devices in the same way may be prima facie obvious. In the case of the instant invention, the prior art of Veres et al teaches a “base” device, upon which the PDMS layer attached to a coverslip can be seen as an improvement. The prior art of Lee teaches a comparable microfluidic device which has been improved in the same way as the claimed invention. One of ordinary skill in the art could have applied the known technique of a PDMS chip attached to a coverslip to the generic chip taught by Veres et al, for the predictable result of creating a device which is supported on a glass base and which can be created using thermoplastic molding techniques.
However, Veres et al in view of Lee et al does not explicitly disclose inlets and outlets having an arc angle ranging from 180 degrees to 300 degrees, the arc angle being structured to prevent cell aggregation in the inlets, the outlets and/or channel surfaces of the donor cell channel and the recipient cell channel.
In the analogous art of microfluidic devices for cell culturing, Petropolis et al teaches;
The claimed “an arc angle ranging from 180 degrees to 300 degrees, the arc angle being structured to prevent cell aggregation in the inlets, the outlets and/or channel surfaces of the donor cell channel and the recipient cell channel” has been read on the taught ([0657], “…one or more of the apertures 211, 215 can be located on one or more lateral surfaces of the first structure and/or second structure such that at least one of the inlet and outlet apertures 211, 215 can be in-plane with the inlet and/or outlet channels 225, 227, respectively, and/or be oriented at an angle from the plane of the inlet and/or outlet channels 225, 227.”; The apertures being in-plane with the channels reads on an arc angle of 180 degrees.)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the device including inlets with the inlets having an arc angle of 180 degrees as taught by Petropolis et al. According to MPEP 2143(I)(C), use of a known technique to improve similar devices in the same way may be prima facie obvious. In the case of the instant invention, the prior art of Veres et al teaches a “base” device, upon which inlets having an arc angle of 180 degrees can be seen as an improvement. The prior art of Petropolis et al teaches a comparable microfluidic device which has been improved in the same way as the claimed invention. One of ordinary skill in the art could have applied the known technique of an inlet or outlet in line with the channels, for the predictable result of providing control input for fluid into the channels.
With regards to claim 2, the device of claim 1 is obvious over Veres et al in view of Lee and further in view of Petropolis et al.
The claimed “wherein the PDMS layer has a thickness of 3-4 mm” has been read on the taught ([0055], “Patterning depth is preferably at least 2-3 times a mean diameter of the cells to be cultured (e.g. 20 to 500 μm), and a thickness of the film 10 is preferably 1.2-10 times the pattern depth.”; 2 – 3 times of 20 to 500 μm creates a range of patterning depth between 40 μm and 1.5mm. 1.2 – 10 times the pattern depth means Veles et al teaches a thickness of 60 μm to 15mm.”
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the device of Veres et al having a thickness in a range of 60 μm to 15mm to have a thickness of 3 – 4 mm as a matter of routine optimization. According to MPEP 2144.05(II)(A), optimization within prior art conditions may be prima facie obvious. In the case of the instant invention, one of ordinary skill in the art would be motivated to create a device with a thickness in the range 3 – 4 mm for sufficient thickness to support the device while minimizing the amount of materials needed in construction.
With regards to claim 3, the device of claim 1 is obvious over Veres et al in view of Lee and further in view of Petropolis et al.
The limitation “wherein the matrix channel is selectively activated by a plasma pulse directed only at the matrix channel using an electrode placed in an outlet of the matrix channel and a tip of a plasma generator placed in an inlet of the matrix channel with inlets and outlets of the donor cell channel and the recipient cell channel being blocked” describes a product-by-process. Please see MPEP 2113.
However, Lee et al further teaches wherein plasma treatment is applied to bond the PDMS chip containing the channel with the coverslip, as read on the taught ([0141], “The PDMS replica was then bonded to precleaned microscope glass slides (Fisher Scientific) through plasma treatment (Harrick Plasma, Cat. No.: PDC-32G.”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the device of claim 1 with the plasma bonded channels as taught by Lee. According to MPEP 2143(I)(D), applying a known technique to a known device ready for improvement to yield predictable results may be prima facie obvious. In the case of the instant invention, the prior art of Veres et al in view of Lee contains a “base” device of a PDMS chip on a coverslip, upon which the claimed plasma bonding can be seen as an improvement. The prior art of Lee et al teaches the technique of plasma bonding. One of ordinary skill in the art would have recognized that applying the known technique of plasma bonding to the system would have yielded the predicable result of an improved system which is fluidically sealed and solidly attached to the base coverslip.
With regards to claim 5, the device of claim 1 is obvious over Veres et al in view of
Veres et al further teaches;
The claimed “wherein inlets and outlets of the donor cell channel and the recipient cell channel are structured to have a gauge such that a seal forms between surfaces of the inlets and surface of an injection device during cell population injection” has been read on the taught ([0086], “…FIG. 4C is a photograph of the chip with 6 ports thereof connected to 6 supply tubes.”; The ports read on an inlet. The supply tubes read on an injection device. Ports connected to a supply tube reads on a surface of the inlet being capable of sealing with an injection device.).
With regards to claim 6, the device of claim 1 is obvious over Veres et al in view of
Veres et al further teaches;
The claimed “wherein the donor cell channel and the recipient cell channel are structured to have a height that prevents cell aggregation in the inlets, the outlets and/or the channel surfaces thereof, the height ranging from 200µm to 400µm” has been read on the taught ([0055], “Patterning depth is preferably at least 2-3 times a mean diameter of the cells to be cultured (e.g. 20 to 500 μm)…”).
With regards to claim 8, the device of claim 1 is obvious over Veres et al in view of
The limitation “wherein inlet and outlet of the matrix channel each comprise a 16 gauge circumference so as to allow a larger pool of the diffusion barrier comprising a hydrogel to be injected into the matrix channels having inlets and outlets with an 18 gauge circumference” relates exclusively to the size of the device. According to MPEP 2144.04(IV)(A), changes in size may be prima facie obvious, provided that a device with the claimed dimensions would not perform differently than the prior art device. In the case of the instant invention, both the inlets taught by Veres et al and the 16 gauge inlets of the claimed invention would allow the insertion of substances into the matrix channel. While a larger gauge may allow a more effective flow, this is a matter of routine optimization, obvious over the prior art of Veres et al in view of Lee in view of Petropolis et al; please see MPEP 2144.05(II)(A).
With regards to claim 9, the device of claim 1 is obvious over Veres et al in view of Lee and further in view of Petropolis et al.
Veres et al further teaches;
The claimed “wherein the matrix channel comprises first and second arrays of transversely spaced-apart matrix ribs, the first array of the transversely spaced-apart matrix ribs is offset from the second array of the transversely spaced-apart matrix ribs by a transverse distance” has been read on the taught ([0059], “The fencing 14 […] may consist of a track of full depth pillars. […] Preferably, elements of the fencing 14 include gaps…”; Fencing pillars read on matrix ribs. The gaps read on a transverse distance between the ribs.).
The limitation “so as to improve diffusion barrier injection into the matrix channel as compared to diffusion barrier injection made into matrix channels having transversely aligned first and second arrays of spaced-apart matrix ribs” is functional language describing the intended use of the device and has been given the appropriate patentable weight. Please see MPEP 2114(II), and Hewlett-Packard Co. v. Bausch & Lomb Inc., 909 F.2d 1464, 1469, 15 USPQ2d 1525, 1528 (Fed. Cir. 1990). As Veres et al teaches all of the structural limitations of the apparatus as defined in claim 9, this additional limitation does not define the instant application over the prior art.
With regards to claim 10, the device of claim 1 is obvious over Veres et al in view of Lee and further in view of Petropolis et al.
Neither Veres et al nor Lee et al does not explicitly disclose wherein the donor cell channel inlet and the recipient cell channel inlet are structured to accommodate target subjects larger than isolated cells, the target subjects comprising tissues or organoids.
Petropolis et al further teaches;
The claimed “the donor cell channel inlet and the recipient cell channel inlet are structured to accommodate target subjects larger than isolated cells, the target subjects comprising tissues or organoids” has been read on the taught ([0049], “In one embodiment, the present invention provides a method of cell culture, comprising […] seeding said cell population on top of said gel so as to create seeded cells; […] In one embodiment, said cells are human organoid cells.”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the device of Veres et al in view of Lee in view of Petropolis et al to have a ports large enough to accommodate tissues or organoids as a matter of routine optimization in view of the prior art of Petropolis et al, which teaches a device suitable for use with organoids. This modification would have the predictable benefit of allowing tissues to be introduced or removed from the device intact.
The limitation “wherein the donor cell channel and the recipient cell channel each comprise inlets having a larger gauge circumference than cell channel inlets structured to accommodate only isolated cells” does not describe a structural feature of the device or a method of intended use, and has been given the appropriate patentable weight.
With regards to claim 11, the device of claim 1 is obvious over Veres et al in view of Lee and further in view of Petropolis et al.
The limitation “wherein the donor or recipient cell population is injected into respective cell channel via a tip of a pipette disposed within respective inlet for a predefined time and volume such that the cell population is transferred from the tip of the pipette to respective cell channel based on gravity, the pipette comprising the cell population” describes the intended use of the device and has been given the appropriate patentable weight. Please see MPEP 2114(II), and Hewlett-Packard Co. v. Bausch & Lomb Inc., 909 F.2d 1464, 1469, 15 USPQ2d 1525, 1528 (Fed. Cir. 1990). As Veres et al teaches all of the structural limitations of the apparatus as defined in claim 11, this additional limitation does not define the instant application over the prior art.
With regards to claim 12, the device of claim 1 is obvious over Veres et al in view of Lee and further in view of Petropolis et al.
The limitation “wherein the donor or recipient cell population is extracted from its respective cell channel via an empty pipette tip disposed within the respective outlet for a predefined volume, the cell population being pushed into the empty pipette tip by injecting cell media into respective inlet via a syringe pump” describes the intended use of the device and has been given the appropriate patentable weight. Please see MPEP 2114(II), and Hewlett-Packard Co. v. Bausch & Lomb Inc., 909 F.2d 1464, 1469, 15 USPQ2d 1525, 1528 (Fed. Cir. 1990). As Veres et al teaches all of the structural limitations of the apparatus as defined in claim 11, this additional limitation does not define the instant application over the prior art.
With regards to claim 13, the device of claim 1 is obvious over Veres et al in view of Lee and further in view of Petropolis et al.
The limitation “wherein the target subject comprises EVs, particles, proteins or nucleic acids, and wherein intercellular communication of the target subject is analyzed for disease progression, utilizing the target subject for delivering medicine, applying therapeutic effects, diagnostic purposes, regenerative medicine, providing immunization against at least infectious diseases or cancer, and any other appropriate investigative research” describes the material worked upon. According to MPEP 2115, “A claim is only limited by positively recited elements. Thus, “[i]nclusion of the material or article worked upon by a structure being claimed does not impart patentability to the claims.” In re Otto, 312 F.2d 937, 136 USPQ 458, 459 (CCPA 1963); see also In re Young, 75 F.2d 996, 25 USPQ 69 (CCPA 1935).” As such, the limitations of claim 13 do not distinguish the claimed invention from the prior art of Veres et al in view of Lee and further in view of Petropolis et al.
With regards to claim 14, Veres et al teaches;
The claimed layer “comprising a plurality of microfluidic channels each having an inlet and an outlet” has been read on the taught ([0057], “Each of the flanking channels 16a,b and the CR 12 has a respective set of two fluid ports 17 (inlets/outlets).”);
The claimed “a matrix channel comprising a diffusion barrier having pores” has been read on the taught ([0053], “The microfluidic device includes a microfluidic chamber with at least one fluid-permeable fencing that divides the chamber into at least 3 volumes. At least one of these volumes contains a porous bed of […] rigid particles (beads).”; [0056], “A central region 12 of the chamber 11…”; Figure 1 shows the central region containing beads.”);
The claimed “the diffusion barrier being structured to mimic extracellular matrix and conduit a target subject from the donor cell channel to the recipient cell channel through the pores” has been read on the taught ([0073], “…a bead bed (a packing mostly consisting of rigid powders…)”; [0073], “The powder is divided into at least two segments, and each of the segments (or any mixture of the segments of different powders) is independently treated with, for example, by surface deposition of proteins, polymers, and other biochemical or organic products… For example, […] extra-cellular matrix (ECM)…”);
The claimed “a donor cell channel structured to receive a donor cell population” and “a recipient cell channel structured to receive at least a recipient cell population” has been read on the taught ([0057], “The fencing 14 separates the chamber 11 into two flanking channels 16a,b…”; [0083], “Cells 50a,b are grown on each side of the bead bed defining respective biowalls.”);
The claimed “an imaging device” has been read on the taught ([0089], “FIG. 6B shows the imaging system with the chip and fluid supply system…”).
However, Veres et al does not explicitly disclose a coverslip, and a Polydimethylsiloxane (PDMS) layer attached to upper surface of the coverslip, or the donor cell channel and the recipient cell channel each comprising inlets and outlets having an arc angle ranging from 180 degrees to 300 degrees, the arc angle being structured to prevent cell aggregation in the inlets, the outlets and/or channel surfaces of the donor cell channel and the recipient cell channel, and an imaging device structured to automatically and continuously acquire images of the target subject within the plurality of microfluidic channels.
In the analogous art of microfluidic cell culture devices, Lee teaches;
The claimed “a coverslip, and a Polydimethylsiloxane (PDMS) layer attached to upper surface of the coverslip” has been read on the taught ([0141], “The PDMS replica was then bonded to precleaned microscope glass slides…”; The PDMS replica of a microfluidic chip reads on a PDMS layer. The microscope glass slides reads on the upper surface of a coverslip.);
The claimed “the PDMS layer comprising a plurality of microfluidic channels each having an inlet and an outlet” has been read on the taught ([0003], “The present disclosure relates to an in vitro microphysiological system comprising a plurality of microfluidic channels…”; [0031], “A channel typically comprises an inlet through which a volume of liquid can be injected. Channels optionally also comprise outlets or vents…”);
The claimed “an imaging device couplable to the microfluidic intercellular communication analysis device and structured to automatically and continuously acquire images of the target subject within the plurality of microfluidic channels for a predefined period upon injection of the donor cell population and the recipient cell population into respective cell channels” has been read on the taught ([0414], “In one embodiment, the optical imaging and video processing provide qualitative and quantitative information regarding biomarkers including, but not limited to, ciliary beat frequency, tissue-wide polarity, mucus flow velocity, and ciliated cell density.”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the device including a microfluidic chip with the PDMS layer and a coverslip as taught by Lee et al. According to MPEP 2143(I)(C), use of a known technique to improve similar devices in the same way may be prima facie obvious. In the case of the instant invention, the prior art of Veres et al teaches a “base” device, upon which the PDMS layer attached to a coverslip can be seen as an improvement. The prior art of Lee teaches a comparable microfluidic device which has been improved in the same way as the claimed invention. One of ordinary skill in the art could have applied the known technique of a PDMS chip attached to a coverslip to the generic chip taught by Veres et al, for the predictable result of creating a device which is supported on a glass base and which can be created using thermoplastic molding techniques.
However, Veres et al in view of Lee et al does not explicitly disclose inlets and outlets having an arc angle ranging from 180 degrees to 300 degrees, the arc angle being structured to prevent cell aggregation in the inlets, the outlets and/or channel surfaces of the donor cell channel and the recipient cell channel.
In the analogous art of microfluidic devices for cell culturing, Petropolis et al teaches;
The claimed “an arc angle ranging from 180 degrees to 300 degrees, the arc angle being structured to prevent cell aggregation in the inlets, the outlets and/or channel surfaces of the donor cell channel and the recipient cell channel” has been read on the taught ([0657], “…one or more of the apertures 211, 215 can be located on one or more lateral surfaces of the first structure and/or second structure such that at least one of the inlet and outlet apertures 211, 215 can be in-plane with the inlet and/or outlet channels 225, 227, respectively, and/or be oriented at an angle from the plane of the inlet and/or outlet channels 225, 227.”; The apertures being in-plane with the channels reads on an arc angle of 180 degrees.)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the device including inlets with the inlets having an arc angle of 180 degrees as taught by Petropolis et al. According to MPEP 2143(I)(C), use of a known technique to improve similar devices in the same way may be prima facie obvious. In the case of the instant invention, the prior art of Veres et al in view of Lee teaches a “base” device, upon which inlets having an arc angle of 180 degrees can be seen as an improvement. The prior art of Petropolis et al teaches a comparable microfluidic device which has been improved in the same way as the claimed invention. One of ordinary skill in the art could have applied the known technique of an inlet or outlet in line with the channels, for the predictable result of providing control input for fluid into the channels.
The limitation “wherein the acquired images are analyzed for intercellular communication of the target subject, and/or functional characterizations for ensuing intercellular communication effects” is functional language describing the intended use of the device and has been given the appropriate patentable weight. Please see MPEP 2114(II), and Hewlett-Packard Co. v. Bausch & Lomb Inc., 909 F.2d 1464, 1469, 15 USPQ2d 1525, 1528 (Fed. Cir. 1990). As Veres et al in view of Lee in view of Petropolis et al teaches all of the structural limitations of the apparatus as defined in claim 14, this additional limitation does not define the instant application over the prior art.
With regards to claim 15, the system of claim 14 is obvious over Veres et al in view of Lee and further in view of Petropolis et al.
Veres et al further teaches;
The claimed “wherein the imaging device comprises a microscope, a camera or other appropriate image capture devices” has been read on the taught ([0089], “FIG. 6B shows the imaging system with the chip and fluid supply system within a (temperature/CO.sub.2 controlled) cell culture incubator of a fluorescence microscope.”).
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Veres et al (US 20200377838 A1) in view of Lee (US 20230147702 A1) in view of Petropolis et al (US 20220106547 A1) as applied to claim 1 above, and further in view of Lee Dong Soo et al (KR 20170067128 A, cited on the PTO-892 with the relied upon translation attached).
With regards to claim 4, the device of claim 1 is obvious over Veres et al in view of Lee and further in view of Petropolis et al.
Veres et al teaches wherein the diffusion barrier includes sections with a variety of pore sizes which are capable of allowing molecules to pass, as read on the taught ([0061], “…it will be appreciated that a divided CR may be desirable, in order to distribute beads of respective functionalizations, sizes, morphology, or other properties in a controlled manner.”; [0093], “This in fact yields a more physiologically relevant interface with which to analyze cell-cell communication in response to biochemical stimuli.”).
However, Veres et al does not explicitly disclose wherein the diffusion barrier comprises a porous hydrogel having a pore size appropriate for passing the target subject from the donor cell channel into the recipient cell channel via the matrix channel, the hydrogel comprising a plurality of hydrogels each having different pore sizes, the plurality of hydrogels comprising at least Matrigel and PEGDA gel.
Lee further teaches;
The claimed “wherein the diffusion barrier comprises a porous hydrogel having a pore size appropriate for passing the target subject from the donor cell channel into the recipient cell channel via the matrix channel” has been read on the taught ([0072], “In embodiments, the extracellular matrix comprises a hydrogel.”);
The claimed “the hydrogel comprising a plurality of hydrogels” has been read on the taught ([0070], “…the extracellular matrix comprises a […] synthetic extracellular matrices, hydrogels, […] or a combination thereof.”);
Lee further teaches the use of Matrigel and PEG [0072], but not the combination of hydrogels.
Neither Veres et al, Lee, or Petropolis et al explicitly discloses the hydrogel comprising a plurality of hydrogels each having different pore sizes, the plurality of hydrogels comprising at least Matrigel and PEGDA gel.
In the analogous art of microfluidic devices Lee Dong Soo et al teaches;
The claimed “plurality of hydrogels each having different pore sizes […] the plurality of hydrogels comprising at least Matrigel and PEGDA gel” has been read on the taught ([0063], “The scaffold used in the first channel according to the present invention refers to a gelled or gelled material that is injected in fluid form and has movable pores…”; [0064], “ Such a scaffold may be selected from the group consisting of […] PEGDA (polyethylene glycol diacrylate), […] Matrigel, […] or a mixture of two or more thereof.”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the device including inlets with the inlets having an arc angle of 180 degrees as taught by Petropolis et al. According to MPEP 2143(I)(C), use of a known technique to improve similar devices in the same way may be prima facie obvious. In the case of the instant invention, the prior art of Veres et al teaches a “base” device, upon which inlets having an arc angle of 180 degrees can be seen as an improvement. The prior art of Petropolis et al teaches a comparable microfluidic device which has been improved in the same way as the claimed invention. One of ordinary skill in the art could have applied the known technique of an inlet or outlet in line with the channels, for the predictable result of providing control input for fluid into the channels.
The limitation of hydrogels having pore sizes “so as to allow for size selection of particles that diffuse across each hydrogel and for determining a population of particles that exert observed functional effects” is functional language describing the intended use of the device and has been given the appropriate patentable weight. Please see MPEP 2114(II), and Hewlett-Packard Co. v. Bausch & Lomb Inc., 909 F.2d 1464, 1469, 15 USPQ2d 1525, 1528 (Fed. Cir. 1990). As Veres et al teaches all of the °structural limitations of the apparatus as defined in claim 4 , this additional limitation does not define the instant application over the prior art.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Veres et al (US 20200377838 A1) in view of Lee (US 20230147702 A1) in view of Petropolis et al (US 20220106547 A1) as applied to claim 1 above, and further in view of Pascual et al (Pascual M, Kordraon M, Rezard Q, Jullien M-C, Champougny L. “Wettability patterning in microfluidic devices using thermally-enhanced hydrophobic recovery of PDMS.” Soft Matter, 2019, 15, 9253).
With regards to claim 7, the device of claim 1 is obvious over Veres et al in view of Lee and further in view of Petropolis et al.
However, this combination does not explicitly disclose wherein the PDMS layer is hydrophobized at a temperature ranging from 180°C to 250°C for a period ranging from 60 minutes to 70 minutes.
In the analogous art of PDMS modification techniques, Pascual et al teaches;
The claimed “wherein the PDMS layer is hydrophobized at a temperature ranging from 180°C to 250°C for a period ranging from 60 minutes to 70 minutes” has been read on the taught (Page 9256, Section 3.1 Temperature dependence of hydrophobic recovery, “The data show that the hydrophobic recovery of PDMS is complete after several months at room temperature, but can be achieved in only a few hours when the baking temperature is increased up to 180°C”; Figure 3 shows a baking time of 60 minutes.).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the PDMS device of Veres et al in view of Lee in view of Petropolis et al with the hydrophobized PDMS layer taught by Pascual et al.
According to MPEP 2143(I)(C), use of a known technique to improve similar devices in the same way may be prima facie obvious. In the case of the instant invention, the prior art of Veres et al teaches a “base” device, upon which the hydrophobized PDMS can be seen as an improvement. The prior art of Pascual et al teaches a comparable PDMS substrate which has been with the same technique as the claimed invention. One of ordinary skill in the art could have applied the known technique of baking the PDMS chip at 180 degrees for 60 minutes, for the predictable benefit of controlling the wettability of the microfluidic chip.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALISON CLAIRE GERHARD whose telephone number is (571)270-0945. The examiner can normally be reached M-F, 9:00 - 5:30pm EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lyle Alexander can be reached at (571) 272-1254. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ALISON CLAIRE GERHARD/ Examiner, Art Unit 1797 /LYLE ALEXANDER/ Supervisory Patent Examiner, Art Unit 1797
Prosecution Insights