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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 3 August 2026 has been entered.
Response to Amendment
This is an office action in response to Applicant’s arguments and remarks filed on 3 August 2026. Claims 1-2, 4-18, 21-23, and 25-39 are currently pending in the application. Claims 21-23 and 25-39 are previously withdrawn. Claims 3, 19-20, and 24 are previously canceled. Claims 1-2 and 4-18 are being examined herein.
Status of Objections and Rejections
The rejection of claims 12-14 under 35 U.S.C. § 112(b) is withdrawn in view of amendments.
The rejections of claims 1, 5-7, and 13-15 under 35 U.S.C. § 103 in view of Chun (KR 20160133812 A; as previously cited in office action dated 16 June 2025) in view of Bien Chia Sheng, et. al. (WO 2012050420 A1; hereinafter Sheng; as previously cited in office action dated 14 August 2025), Van Reis ( US 20020108907 A1), and Gagnon (US 20170173537 A1) are withdrawn in view of amendments.
The rejection of claim 2 under 35 U.S.C. § 103 in view of Chun (KR 20160133812 A; as previously cited in office action dated 16 June 2025) in view of Bien Chia Sheng, et. al. (WO 2012050420 A1; hereinafter Sheng; as previously cited in office action dated 14 August 2025), Van Reis ( US 20020108907 A1), and Gagnon (US 20170173537 A1) in further view of Kim (US 20170088807 A1; as previously cited in office action dated 16 June 2025) are withdrawn in view of amendments.
The rejections of claims 4, 8-12, and 16-18 under 35 U.S.C. § 103 in view of Chun (KR 20160133812 A; as previously cited in office action dated 16 June 2025) in view of Bien Chia Sheng, et. al. (WO 2012050420 A1; hereinafter Sheng; as previously cited in office action dated 14 August 2025), Van Reis ( US 20020108907 A1), and Gagnon (US 20170173537 A1) in further view of Issadore, et. al. (US 20160158756 A1; as previously cited in office action dated 16 June 2025) are withdrawn in view of amendments.
Response to Arguments
Applicant’s arguments, see Remarks, page 10, par. 07 – page 12, par. 01, filed 3 August 2026, with respect to the rejections of claims 1, 5-7, and 13-15 under 35 U.S.C. § 103 in view of Chun (KR 20160133812 A; as previously cited in office action dated 16 June 2025) in view of Bien Chia Sheng, et. al. (WO 2012050420 A1; hereinafter Sheng; as previously cited in office action dated 14 August 2025), Van Reis ( US 20020108907 A1), and Gagnon (US 20170173537 A1) have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Kameoka, et. al. (US 20220364076 A1; provision filing date of 2 July 2019) in view of Tringe, et. al. (US 20130306549 A1) and Yen, (US 4968429 A).
Applicant offers no additional arguments against Kim and Issadore aside from not curing deficiencies present in independent claim 1 (Remarks, pg. 11). Examiner continues to present Kim and Issadore as prior art for rejections of dependent claims (see below).
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1, 5-6, and 12-15 are rejected under 35 U.S.C. 103 as being unpatentable over Kameoka, et. al. (US 20220364076 A1; provision filing date of 2 July 2019) in view of Tringe, et. al. (US 20130306549 A1) and Yen, (US 4968429 A).
Regarding claim 1, Kameoka teaches a microfluidic platform for selective isolation of a flowing sample (Abstract) specifically for isolation of exosomes (par. 0031) (a system for isolating exosomes). Kameoka teaches the microfluidic platform comprises a top channel layer and a center channel layer separated by a first porous membrane creating horizontally aligned microchannels (a first chamber) (a second chamber) separated by the first porous membrane (a membrane) (Fig. 1B, 4A; par. 0034) (a membrane positioned between the first and second chambers). The first porous membrane has a first side/surface that faces the microchannel in the top layer (and comprising a first membrane surface facing and at least partially defining the first chamber) and a second side/surface that faces the microchannel of the center channel layer (a second membrane surface facing and at least partially defining the second chamber) (Fig. 1B, 4A). Kameoka teaches the first porous membrane comprises a plurality of pores having a first pore size, wherein the pores extend through the entire thickness of the membrane (Fig. 1B; 4A; par. 0034) (a plurality of… nanopores extending between the first and second membrane surfaces). Kameoka teaches the first pore size to be 100 nm (par. 0035) (wherein each nanopore includes a first nanopore opening at the first membrane surface having a first diameter of between about 5 nm and about 300 nm).
Kameoka teaches the microchannel of the top layer extends across a top surface of the first porous membrane and has a top inlet at one end of the microchannel and an outlet at a second, opposite end of the microchannel (Fig. 1A-B) (wherein the first chamber defines a flow channel extending longitudinally along the first membrane surface, the flow channel comprising an inlet and an outlet). As seen in Figure 4A, a flow is created that extends in a parallel direction over the top surface of the first porous membrane (configured to direct tangential fluid flow in a direction parallel to the first membrane surface).
Kameoka teaches the sample is first applied to the microchannel of the top channel layer (Fig. 2) (a sample comprising exosomes positioned within the first chamber), wherein the sample comprises exosomes from patient samples (par. 0055-0056) (the sample comprising one or more of… a sample obtained from an animal subject).
Kameoka teaches a general pumping systems fluidically connected to the microchannels, wherein a first solution (a sample or test solution serving as a sample) is pumped into the top microchannel and a buffer solution is pumped into the center microchannel (par. 0042) (pump fluidically coupled to the tangential-flow filtration chip and configured for inducing… flow of the sample across the membrane in the first chamber) (pump fluidically coupled to the tangential-flow filtration chip and configured for inducing tangential fluid flow of a… buffer solution… in a direction along… the membrane). This implies the pumping of the sample and the buffer are separated. Kameoka teaches the system is configured for exosomes of less than 150 nm (par. 0058) and move from the top microchannel to the second microchannel (Fig. 4A) (exosomes having a diameter of about 50 nm to about 200 nm are isolated from the sample in the second chamber).
Kameoka is silent to the nanopore being an asymmetrically shaped nanopores; wherein the a second nanopore opening at the second membrane surface having a second diameter that is greater than the first diameter but less than about 5 µm.
Tringe teaches a nanoporous membrane with an array of frustum-shaped pores (Abstract) to be used for filtration/isolation of samples (par. 0003). Tringe teaches the porous array having a "predetermined width that is substantially a function of the desired pore size" (Fig. 14, 15; par. 0010) (a plurality of asymmetrically shaped nanopores extending between the first and second membrane surfaces). Tringe teaches the pore widths/diameters are highly tunable based on desired pore size (the smaller opening) (par. 0057). Tringe teaches pore formation follows the equation
w
2
=
w
1
-
2
tan
θ
d
, wherein w2 is the pattern width (equivalent to the larger pore width/diameter), w1 is the pore width (equivalent to the smaller pore width/diameter), and d is the thickness of the silicon (par. 0054-0055). Tringe teaches a method where the pattern width/larger pore size (a second nanopore opening) is 1 µm to create a pore size/smaller pore size (a first nanopore opening) on a nanometer-sale (par. 0055) (and a second nanopore opening at the second membrane surface having a second diameter that is greater than the first diameter but less than about 5 µm). As seen in Figure 15, Tringe teaches the nanopore is frustum-shaped wherein the flow direction for the completed membrane directs the fluid through the smallest opening first and the largest opening second. Tringe teaches this flow direction minimizes fouling and increases flow rates through the pores (par. 0058).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to modify the shape of the pore in the membrane of Kameoka to be asymmetrically shaped nanopores, wherein the a second nanopore opening at the second membrane surface has a second diameter that is greater than the first diameter as taught by Tringe because the asymmetric shape prevents fouling on the membrane through increased flow rates through the pores (Tringe, par. 0058) with reasonable expectation of success. MPEP § 2143(I)(G).
Modified Kameoka is silent to a first pump fluidically coupled to the tangential-flow filtration chip and configured for inducing tangential fluid flow of a recirculating buffer solution through the flow channel in a direction along the first membrane surface; and a second pump fluidically coupled to the tangential-flow filtration chip and configured for inducing pressure driven flow of the sample across the membrane in the first chamber; wherein the first pump and the second pump are configured to operate simultaneously such that: the first pump induces tangential fluid flow of the recirculating buffer solution through the flow channel in a direction along the first membrane surface; and the second pump induces pressure driven flow of the sample in a direction through the asymmetric conically-shaped nanopore of the membrane.
Examiner notes it is specifically the bolded limitations that are not taught or fairly disclosed by Kameoka in view of Tringe.
Yen teaches a filtering method and apparatus for generating pressure through pump to generate flow across a membrane wherein positive pressure causes a portion of the suspension to pass through the membrane to be collected/isolated from the bulk suspension (Abstract). Yen teaches a flow filter arrangement 140 comprising a first pump 146 downstream filter 148 and is configured to recirculate suspension 142 from a holding tank 144, through the filter 148, across the filter membrane 150 (tangentially), and back to holding tank 144 through negative pressure (Fig. 3; col. 10, lines 6-26) (a first pump fluidically coupled to the tangential-flow filtration chip and configured for inducing tangential fluid flow of a recirculating buffer solution through the flow channel in a direction along the first membrane surface) (wherein the first pump… are configured to operate simultaneously such that: the first pump induces tangential fluid flow of the recirculating buffer solution through the flow channel in a direction along the first membrane surface). Yen teaches the system further comprises a second pump 160 that generates a positive pressure to allow a filtrate (or permeate or particle of interest) to pass through the filter membrane (Fig. 3, col. 10, lines 25-40) (a second pump fluidically coupled to the tangential-flow filtration chip and configured for inducing pressure driven flow of the sample across the membrane in the first chamber) (the second pump induces pressure driven flow of the sample in a direction through the asymmetric conically-shaped nanopore of the membrane). Yen teaches the second pump to generate a positive pressure that moves the sample fluid, particularly the particle of interest through the membrane, when paired with the first pump to generate a negative pressure to move bulk fluid across the membrane prevents clogging (col. 4, line 66 - col. 5, line 26).
It would have been obvious for one or ordinary skill in the art before the effective filing date of the invention to modify the pumping system of modified Kameoka to comprise at least two pumps, a first pump for inducing tangential fluid flow of a recirculating solution across a first membrane surface and a second pump to induce a pressure driven flow across/through the membrane as taught by Yen because the two pressures from the two pumps prevents clogging of the filtration membrane (Yen, col. 4, line 66 - col. 5, line 26) with reasonable expectation of success. MPEP 2143(I)(G).
Examiner notes the second pump is only functionally required to induce a pressure driven flow of the sample across the membrane in the first chamber. In other words, the second pump generates a pressure that moves the sample fluid across the membrane (from the first chamber to the second chamber) through creating a pressure differential. Examiner notes this can be done (as taught by Yen) without the second pump pumping the sample fluid itself. Therefore, the first pump can pump the buffer solution AND the sample solution.
Regarding claim 5, modified Kameoka teaches the first pore size to be 100 nm (Kameoka, par. 0035) (wherein the first diameter is between about 10 nm and about 200 nm).
Regarding claim 6, modified Kameoka in view of Tringe teaches a method where the pattern width/larger pore size (a second nanopore opening) is 1 µm to create a pore size/smaller pore size (a first nanopore opening) on a nanometer-sale (Tringe, par. 0055) (wherein the second diameter is less than about 2 µm).
Regarding claim 7, modified Kameoka teaches the porous membranes is made of polycarbonate (Kameoka, par. 0039) (wherein the membrane is formed from one or more materials comprising one or more of… a polycarbonate (PC)).
Regarding claim 12, modified Kameoka teaches a solution is pumped into the top microchannel at a flow rate of 5 µL/min (corresponding to 0.3 mL/hr) (Kameoka, par. 0042) to up to 20 µL/min (1.2 mL/hr) (Kameoka, par. 0051) (wherein the first pump generates a flow rate of between about 0.01 mL/hour to about 1000 mL/hour).
Regarding claim 13, modified Kameoka in view of Yen teaches first pump 146 generates a negative pressure to move fluid through the filtration system, wherein the system has an overall negative pressure to prevent clogging of the filter membrane (Yen, col. 10, lines 30-40) (wherein the first pump generates a pressure less than about 1 atm).
Regarding claim 14, modified Kameoka teaches miniaturized versions of common macro-pump systems can be used to minimize size (Kameoka, par. 0030) (wherein the first pump comprises… a micropump).
Regarding claim 15, modified Kameoka teaches the top microchannel receives a bulk sample fluid wherein a first portion of the bulk sample fluid comprising smaller particles passes through the nanoporous filter membrane and a second portion of the bulk sample fluid comprising larger particles passes across the surface of the nanoporous membrane (Kameoka, Fig. 2, 4A) (wherein a first portion of the sample passes through the membrane or filter and a second portion of the sample passes parallel to the membrane). Modified Kameoka in view of Yen teaches the solution that does not pass through the filter membrane is recirculated (Yen, Fig. 3; col. 10, lines 6-26) (a second portion of the sample… is recirculated).
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Kameoka, et. al. (US 20220364076 A1; provision filing date of 2 July 2019) in view of Tringe, et. al. (US 20130306549 A1) and Yen, (US 4968429 A) as applied to claim 1 above, and further in view of Kim (US 20170088807 A1; as previously cited in office action dated 16 June 2025).
Regarding claim 2, modified Kameoka teaches the top channel layer has an upper surface of PDMS (a wall) opposite to the first porous membrane (Fig. 2) (wherein the first chamber comprises a wall opposite of the first membrane surface). Kameoka teaches electrodes are used in the microchannel to indue elastic life force to encourage particles through the membrane filters (par. 0028).
Modified Kameoka is silent to wherein the wall comprises one or more baffles.
Kim teaches a multichannel microfluidic device with membranes to mimic a biomolecular environment (par. 0006-0009). Kim teaches within the chambers there are baffles 425 along the wall of the channel 421 opposite to the porous membrane 430 (wherein the first chamber comprises a wall opposite of the first membrane surface that comprises one or more baffles) (Fig. 5; par. 0040). Kim teaches these baffles induce dynamic mixing of the sample (par. 0009) as well as provide structural integrity to the channel (par. 0039).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to modify the wall opposite to the nanopore membrane of Chun to include baffles as taught by Kim because doing so would dynamically mix the sample and provide structural supported to the stacked layers (Kim, par. 0009, 0039) with reasonable expectation of success. MPEP § 2143(I)(G).
Further, it would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to substitute the electrodes for inducing flow through the membranes of modified Kameoka to instead be baffles on a wall opposite the membrane as taught by Kim. One would be motivated to do so because baffles dynamically mix the sample and provide structural supported to the stacked layers (Kim, par. 0009, 0039) and involves the simple substitution of one known element (electrodes) for another (baffles) to obtain predictable results (dynamic mixing of fluid in microchannel). MPEP 2143(I)(B).
Claims 4, 8-11, and 16-18 are rejected under 35 U.S.C. 103 as being unpatentable over Kameoka, et. al. (US 20220364076 A1; provision filing date of 2 July 2019) in view of Tringe, et. al. (US 20130306549 A1) and Yen, (US 4968429 A) as applied to claim 1 above, and further in view of Issadore, et. al. (US 20160158756 A1; as previously cited in office action dated 16 June 2025).
Regarding claim 4, modified Kameoka teaches the limitations as applied to claim 1 (see above).
Modified Kameoka is silent to wherein the first membrane surface is coated with a magnetic alloy.
Issadore teaches a magnetic separation device with a membrane with pores (Abstract). Issadore teaches a separation device comprising open layers (first chamber, second chamber) separated by a membrane with a plurality of pores embedded into the membrane (membrane positioned between the first and second chambers... plurality of nanopores). Issadore teaches a magnetic material layered along the top of the membrane surface (wherein the first membrane surface is coated with a magnetic alloy) (Fig. 1a, 4a; par. 0032). Issadore teaches the addition of a magnetic alloy to the surface of the membrane improves sorting efficiency and greater throughput while keeping costs low (par. 0006).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to modify the nanopore membrane of Chun to include a magnetic alloy as taught by Issadore because doing so would increase efficiency and throughput of the separation device (Issadore, par. 0006) with a reasonable expectation of success. MPEP § 2143(I)(G).
Regarding claim 8, modified Kameoka teaches wherein the device can comprise a plurality of layers for filtering, thus creating a plurality of center chambers and center layers (Kameoka, par. 0008).
Modified Kameoka is silent to a third chamber and a filter positioned between the third chamber and the first chamber and the filter comprising a first filter surface facing and at least partially defining the third chamber, a second filter surface facing and at least partially defining the first chamber and a plurality of filter pores extending between the first and second filter surfaces.
Issadore teaches a magnetic separation device with a membrane with pores (Abstract). Issadore teaches a separation device comprising open layers (first chamber, second chamber) separated by a magnetic filter membrane with a plurality of pores embedded into the membrane (membrane positioned between the first and second chambers... plurality of nanopores) (Fig. 1a, 4a; par. 0032). Issadore teaches an embodiment that comprises up to 10 layers of the magnetic filter membrane with an open space between each layer (a third chamber and a filter positioned between the third chamber and the first chamber) (par. 0056). Each magnetic filter membrane helps define the open layers they separate (the filter comprising a first filter surface facing and at least partially defining the third chamber, a second filter surface facing and at least partially defining the first chamber and a plurality of filter pores extending between the first and second filter surfaces) (Fig. 4a). Issadore teaches adding more layers of filter membranes increases the enrichment of the sample after each additional layer (par. 0056).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to modify the two chambers and nanopore membrane of modified Kameoka in include a third chamber with a second filter membrane with a plurality of pores between the first and third chamber, as taught by Issadore because doing so would increase enrichment of the sample through each pass through of a filter (Issadore, par. 0056) with a reasonable expectation of success. MPEP § 2143(I)(G).
Regarding claim 9, modified Kameoka in view of Issadore teaches the pores in the membrane filter range from 100 nm to 100 µm (Issadore, par. 0007; 0038). Issadore teaches the pore size selected based on sample (Issadore, par. 0038-0039). Since this particular parameter is recognized as result-effective variable, i.e., a variable which achieves a recognized result, the determination of the optimum or workable ranges of said variable can be characterized as routine experimentation. MPEP § 2144.05(II)(A)-(B). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filling date of the invention through routine optimization for the diameter of the pores of the filter membrane to be between 200 nm to 5 microns to create nanopores to accommodate the size of the molecules in the sample.
It additionally would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to modify the diameter of the second pore as taught by Issadore because doing so would allow for the pore size to be optimized for the biomolecules in the sample with a reasonable expectation of success. MPEP § 2143(I)(G). Furthermore, in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP § 2144.05(I).
Regarding claim 10, modified Kameoka in view of Issadore teaches the filters are made of polycarbonate (Issadore, par. 0066) (wherein the filter is formed from one or more materials comprising... polycarbonate (PC)).
Regarding claim 11, modified Kameoka teaches a second porous membrane (a second membrane) opposite the first porous membrane (the membrane), wherein the second porous membrane has a first surface defining a bottom of the center microchannel (the second chamber) and a second surface defining a top of the bottom microchannel (a fourth chamber) (Kameoka, Fig. 1B, 4A; par. 0034) (further comprising a fourth chamber and a second membrane positioned between the fourth chamber and the second chamber) (the second membrane comprising a first surface… at least partially defining the second chamber and a second surface facing and at least partially defining the fourth chamber).
Modified Kameoka is silent to the second membrane comprising a first surface coated with a magnetic alloy.
Issadore teaches a magnetic separation device with a membrane with pores (Abstract). Issadore teaches a separation device comprising open layers (second chamber, fourth chamber) separated by a membrane with a plurality of pores embedded into the membrane (membrane positioned between the fourth and second chambers). Issadore teaches a magnetic material layered along the top of the membrane surface (the second membrane comprising a first surface coated with a magnetic alloy) (Fig. 1a, 4a; par. 0032). Issadore teaches the addition of a magnetic alloy to the surface of the membrane improves sorting efficiency and greater throughput while keeping costs low (par. 0006).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to modify the second membrane of modified Kameoka to include a first surface coated with a magnetic alloy as taught by Issadore because doing so would increase efficiency and throughput of the separation device (Issadore, par. 0006) with a reasonable expectation of success. MPEP § 2143(I)(G).
Regarding claim 16, modified Kameoka in view of Issadore teaches the magnetic layer is a nickel and iron alloy (Issadore, par. 0045) (wherein the magnetic alloy is nickel- iron).
Regarding claim 17, modified Kameoka teaches the system is specifically for isolation of exosomes (Kameoka, par. 0031).
Modified Kameoka is silent to wherein the exosomes are bound to a probe that is coupled to a magnetic bead.
Issadore teaches bacteria are tagged with a magnetic nanoparticle that will influence how the sample interacts with the magnetic filters. The magnetic nanoparticles used for tagging interact with antibodies (wherein the exosomes are bound to a probe that is coupled to a magnetic bead) (par. 0068). This allows the biological sample to interact with the magnetic filter membrane to separate the sample (0077-0082).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to modify the exosome sample of modified Kameoka to include a probe (antibody) coupled with a magnetic bead (magnetic nanoparticle) as taught by Issadore because doing so allows the sample to interact with the magnetic filter membrane (Issadore, 0077-0082) with a reasonable expectation of success. MPEP § 2143(1)(G).
Regarding claim 18, modified Kameoka in view of Issadore teaches the magnetic nanoparticles used for tagging interact with antibodies (the probe is an antibody) (Issadore, par. 0068, 0077-0082).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MADISON T HERBERT whose telephone number is (571)270-1448. The examiner can normally be reached Monday-Friday 8:30a-5:00p.
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, Maris Kessel can be reached at (571) 270-7698. 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.
/M.T.H./Examiner, Art Unit 1758
/MARIS R KESSEL/Supervisory Patent Examiner, Art Unit 1758
Prosecution Insights