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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 10/01/2025 has been entered.
Claim Status
1. The amendment filed 10/01/2025 has been entered. Claims 1 – 18 and 22 remain pending.
Election/Restrictions
2. Applicant’s election without traverse of Group I (claims 1 – 20) in the reply filed on 09/12/2024 is acknowledged.
3. Claim 22 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 09/12/2024.
4. Claims 1 – 18 are under consideration.
Priority
5. The present application is US national stage of international application PCT/US2019/031738 which has an international filing date of May 10, 2019, and which claims the benefit of US. Provisional Patent Application No. 62/670,839, filed on May 13, 2018.
Withdrawn Claim Objections
6. The objection to claim 1 is withdrawn in view of Applicant’s amendment to the claim.
Withdrawn Claim Rejections
7. The rejection of claims 1 and 3 – 18 under 35 U.S.C. 103 is withdrawn in view of the amendment to claim 1 to require “at least one channel wall of a flow channel flowing the sample is chemically modified to be non-adherent or repulsive”.
8. The rejection of claim 2 under 35 U.S.C. 103 is withdrawn in view of the amendment to claim 1 to require “at least one channel wall of a flow channel flowing the sample is chemically modified to be non-adherent or repulsive”.
New 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.
9. Claim 1 – 11 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
10. Regarding claim 1, it is unclear how at least one channel wall is chemically modified to be non-adherent or repulsive for any claimed particle. The specification teaches chemical modification of channel walls to reduce non-specific adsorption of cells or compounds e.g. released by lysed cells or found in biological samples onto the walls but also teaches that the type of chemical species used for repulsion can depend on the nature of the species being repelled and the nature of the walls and the species being attached (page 19, lines 1 – 12). For the purpose of applying prior art, this limitation is interpreted as a channel wall is chemically modified with one of the chemical species listed in the specification at page 19, lines 3 – 8. Claims 2 – 11 are also rejected as they depend from claim 1 and do not clarify the grounds of rejection.
11. Regarding claim 5, it is unclear if “an inlet” in line 2 and “the inlet” in line 3 refers to either or both of the “separate inlets” recited in claim 1 or is another inlet. Further, it is unclear if the claim is further limiting step b of claim 1 to require that the sample and wash fluid do not flow through the device simultaneously. For the purpose of applying prior art, “an inlet” of claim 5 is interpreted as either the “separate inlets” recited in claim 1 because panels 1 – 3 of Figure 3 of Applicant’s disclosure shows flow from the product reservoir through the inlets.
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.
12. Claim(s) 1 and 3 – 18 are rejected under 35 U.S.C. 103 as being unpatentable over Aurich (WO2017035262A1; previously cited), hereinafter Aurich which is cited on the IDS filed 03/28/2021, in view of Reichenbach (US20100006479A1; Filed 07/09/2009, Published 01/14/2010; previously cited), hereinafter Reichenbach which is cited on the IDS filed 11/05/2024 in view of Grisham (WO2016019393A1; Filed 03/08/2015; Published 02/04/2016), hereinafter Grisham which is cited on the IDS filed 03/28/2021.
Regarding claim 1, Aurich teaches a method of separating particles from a sample comprising applying the sample and buffer to a microfluidic device at separate inlets (step a) (page 1, 0004; page 28, 0069; Figure 24). Aurich teaches the buffer can comprise the same components as the sample except the particles to be concentrated in the device (step a(i)) (page 29, 0069). Aurich teaches the device comprises an array of obstacles arranged in rows, with each subsequent row of obstacles shifted laterally with respect to a previous row (“array of obstacles arranged in rows” of step a(ii)) (Figure 2). Aurich teaches in Figure 2 differential deflection of large and small cells (“differentially deflect” of step a(ii)) (Figure 2). Aurich teaches a first array of obstacles configured to allow first particles of at least a critical size to flow in a first direction to a first outlet and second particles of less than the critical size to flow in a second direction to a second outlet (“first outlet” and “second outlet” of step a(ii)) (page 8, 0017; Figure 24). Aurich teaches passing the first particles and the second particles comprises passing the sample through a deterministic lateral displacement (DLD) array and further comprises passing a buffer into the system (step b) (page 4, 0008). Aurich teaches the method further comprises collecting the particle of interest into a particle collector (step c of claim 1) (page 17, 0026). Aurich teaches a method comprising flowing a sample through a DLD array of obstacles in a microfluidic channel where the DLD array can deflect particles of at least a critical size in the sample to a product outlet of the microfluidic channel and a portion of the sample that does not contain the particles can flow out of the microfluidic channel through one or more waste outlets (page 29, 0069). Aurich teaches when collected in a solution flowed out of the microfluidic channel through the product outlet, the particles of at least the critical size can be concentrated in solution and the particles of less than the critical size can be deflected to a waste outlet (page 29, 0069). Aurich does not teach “at least a portion of the target cell or target particle product is recirculated one or more times to replace, all, or at least a portion, of the wash fluid being applied to the device” of step b or “wherein in the step b), the number of recirculation is adjusted based on an initial concentration of the target cells or target particles and a desired output concentration of the target cells or target particles” in step c or “at least one channel wall of a flow channel flowing the sample is chemically modified to be non-adherent or repulsive”.
Regarding claim 3, Aurich teaches the buffer is 1% KP/10 mM EDTA/PBS (page 140, 0452 – 0454; page 141, 0455 – 0456).
Regarding claim 4, Aurich teaches a first outlet (page 8, 0017; Figure 24) but does not teach the first outlet comprises or is connected to a valve.
Regarding claim 5, Aurich teaches separate buffer and sample inlets (Figure 24) but does not teach either inlet is connected to a valve.
Regarding claim 6, Aurich teaches in Example 1 separating white blood cells (“target cell”) from a whole blood sample where the sample is mixed with labeling solution resulting in white blood cells in the sample being bound by magnetic beads-conjugated with anti-CD45 antibodies (“antibody”) and the sample is applied to the microfluidic device (page 128, 0386). Aurich does not teach “recirculated”.
Regarding claims 7 and 12 – 14, Aurich teaches in Example 1, collecting a whole blood sample from a patient and separating white blood cells (“blood” and “apheresis or leukapheresis on blood” claim 14) and circulating tumor cells (CTCs) using a DLD array with a critical size of no more than 5 µm where the white blood cells and CTCs (“target cells of a predetermined size” of claim 12 and “leukocytes” of claim 13) are separated from smaller platelets (“cells less than the predetermined size” of claim 12 and “platelets” of claim 13) by the DLD array (page 128, 0386 – 0387). Aurich teaches red blood cells and white blood cells are at least 3 µm and platelets are less than 3 µm (“predetermined size” of claim 12) (page 133, 0413). Aurich teaches the number of CTCs is counted (claim 7) to generate a diagnosis of cancer for the patient (page 128, 0388).
Regarding claims 8 – 10, Aurich teaches in Example 11 enriching rare cells from blood and that the DLD array concentrates the rare cells by 10 times (“a factor of at least 3” of claim 8; “a factor of at least 5” of claim 9; “a factor of at least 10” of claim 10) (page 134, 0419; Figure 10D). Aurich teaches the particles can be concentrated by greater than or about 3, 5, or 10-fold compared to the concentration of the particles in the sample (page 117, 0346). Aurich does not teach “recirculation”.
Regarding claim 11, Aurich teaches the parameters affecting concentration factor include the ratio of volume flowing through the waste outlets to the volume flowing through the product outlets and teaches ratios can be 1:100 to 100: 1 (page 117, 0347). Aurich teaches the longer and/or wider the DLD arrays are, the higher the concentration factor (page 117, 0347). Aurich teaches DLD arrays with lower tilt or that are less resistive can achieve a higher concentration factor (page 117, 0347). Aurich does not teach other methods besides microfluidic processing for concentrating cells, however, Aurich does not teach “recirculation”.
Regarding claim 15, Aurich teaches in Example 1 a whole blood sample is mixed with labeling solution resulting in white blood cells (“leukocytes”) in the sample being bound by magnetic beads-conjugated anti-CD45 antibodies (“antibody”) (page 128, 0386). Aurich teaches after passing the sample through the DLD array, the fraction comprising white blood cells and CTCs is then passed to a magnetic separator (“in a way that promotes or complements DLD separation”) wherein the white blood cells are separated from the CTCs (page 128, 0387). Aurich does not teach the leukocytes are being recirculated.
Regarding claims 16 and 17, Aurich teaches the particles can be CAR-T cells (“T cells” of claim 16 and “CAR-T cells of claim 17) and the systems and devices can be used to enrich CAR-T cells (page 98, 0280; page 101, 0287).
Regarding claim 18, Aurich teaches the method does not require density centrifugation techniques (page 36, 0084).
Aurich does not teach recirculation of step b of claim 1, and claims 6, 8 – 11, and 15, or “wherein in the step b), the number of recirculation is adjusted based on an initial concentration of the target cells or target particles and a desired output concentration of the target cells or target particles” of step c of claim 1 or “at least one channel wall of a flow channel flowing the sample is chemically modified to be non-adherent or repulsive” of claim 1, or “valve” of claims 4 and 5. However, Aurich teaches a method for concentrating particles by greater than 50-fold comprising flowing the sample through a microfluidic channel from the first inlet to a plurality of outlets where the channel comprises one or more arrays of obstacles to deflect the (page 17, 0027; page 132, 0407 – 0409). Aurich teaches a sample can comprise one or more additives to facilitate safe and effective processing through the system including polymers including Pluronic F127 (page 86, para. 0238; page 87, para. 0244). Aurich teaches in Figure 7B – C the concentration of cells before passing through the array (6 x 103 cells/mL for sample 1 and 6 x 102 cell/mL for sample 2) (page132, 0407 – 0410). Aurich teaches the particles can be concentrated by greater than or about 1.5, 2, 2,5, 3 – 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 200, 500, 1000, 2000, 3000, 4000, 5000, 6000, 7000, 8000, 9000, 10,000, or 15,000-fold compared to the concentration of the particles in the sample (page 117, 0346). Aurich teaches a concentrating device can comprise multiple DLD arrays where each array can concentrate a sample for the same or different folds (page 56, 0139). Aurich teaches a concentrator can comprise two or more different DLD arrays and each stage can concentrate particles about or at least 2 – 5000-fold where different stages of a concentrator can concentrate particles at different levels or the same level (page 57, 0141). Aurich teaches a system for enriching particles comprising a concentrator comprising an inlet, a second array of obstacles, and a product outlet wherein the second array of obstacles is configured to deflect the fourth particles to produce a solution at a higher concentration compared to in the sample (page 19, 0029). Aurich teaches isolation and enrichment of rare cells and particles from bodily fluids can be used to understand the concentration, function, and genomic composition of the rare cells and particles and can provide information for diagnosing and treating diseases such as cancer (page 1, 0003). Aurich teaches given the low concentration of rare cells or particles within biological samples, some form of positive or negative selection or enrichment is needed to detect and/or quantify rare cells or particles (page 1, 0003). Aurich teaches an integrated, automated process that that gently and uniformly processes cells and particles with virtually no cell loss is needed to achieve consistent reliable clinical information for diagnosing and treating disease (page 1, 0003).
Regarding recirculation and “valve” of step b of claim 1, and claims 4, 5, 6, 8 – 11, and 15 and “wherein in the step b), the number of recirculation is adjusted based on an initial concentration of the target cells or target particles and a desired output concentration of the target cells or target particles” of claim 1c, Reichenbach teaches a method and device for dispersing particles that may be cells suspended in a fluid using an obstacle field where dispersion of the particles is caused by an asymmetrical interaction with the obstacles that results in an asymmetrical particle shifting where the obstacle field separates particles by size (page 1, 0024; page 2, 0028; Figure 1 and 4; page 6, 0058 – 0059; Figure 12 – 13). Reichenbach teaches in order to achieve the final particle concentrations desired from the separation process, the particle rich effluent may be re-circulated (“recirculation” of step b of claim 1, and claims 6, 8 – 11, 15) where it is returned to the entrance of the device by a pumping or valving system (“valve” of claims 4, 5) as shown in Figure 14 (page 6, 0060 – 0061). Reichenbach teaches the device comprises a re-circulating flow field that allows at least a portion of the fluid flow to reenter the obstacle field (page 2, 0029). Reichenbach teaches the device includes a conduit having one or more inlets and one or more outlets (page 2, 0028). Reichenbach teaches the method may be used in the areas of microfluidics, blood components processing, and recovery of cells in biotechnological processes (page 2, 0024). Reichenbach does not teach “at least one channel wall of a flow channel flowing the sample is chemically modified to be non-adherent or repulsive” of claim 1. One would have been motivated to combine the teachings of Aurich and Reichenbach because both teach methods of concentrating cells by sorting using microfluidic devices with an array of obstacles and both teach the method and device can be used for processing blood components.
Regarding “at least one channel wall of a flow channel flowing the sample is chemically modified to be non-adherent or repulsive” of claim 1, Grisham teaches a method for microfluidic processing of blood by deterministic later displacement (DLD) arrays where to reduce non-specific adsorption of cells or compounds, e.g., released by lysed cells or found in biological samples, onto the channel walls, one or more channel walls may be chemically modified to be non-adherent or repulsive (page 130, para. 00507; page 131, para. 00507). Grisham teaches the walls may be coated with a thin film coating of commercial non-stick reagents, such as those used to form hydrogels or fluorinated polymers or heparin can be deposited from solution onto PDMS to make channels hydrophilic while preventing adhesion of blood cells and proteins (page 130, para. 00504 and 00505; page 131, para. 00507). Grisham teaches rinsing the system and tubing with Pluronic F108 surfactant prior to introducing the sample solution (page 188, para. 00748). Grisham teaches surfactants such as Pluronic can be used to make surface protein repellant by adding Pluronic to PDMS formulations during the device fabrication (page 129, para. 00503; page 168, para. 00679). Grisham teaches the device has three inlets for sample, an aqueous washing buffer, and staining chemicals and outlets for product and waste for processing blood (Figure 48A; page 186, 00740; page 187, para. 00743; page 188, para. 00750). Grisham teaches the device has an array of posts where cells (red blood cells due to their shape, platelets, protein) smaller than a critical size (6 µm) can follow the stream waving around the posts and target cells (leukocytes) larger than this critical size bump into the posts and move into the treatment stream for staining with rhodamine 6G (R6G) and then collected as product output (page 187, para. 00743; Figure 48A – B; page 188, para. 00748 – 00750; page 191, para. 00762). Grisham teaches the method separates and stains leukocytes with R6G from diluted whole blood (page 191 – 192, para. 00762; Figure 50 – 51). Grisham teaches concentrating the leukocytes in the device and collecting the leukocytes at the product output where a good separation was indicated by fluorescence imaging and the leukocytes had low contamination (page 192, para. 00762). Grisham teaches the method does not require any pre-processing of the blood or manual handling between steps (page 192, para. 00764). Grisham teaches there is a need for improved methods for chemical and/or enzymatic treatment, washing, and isolation of cells (page 1, para. 0003 – 0005). Grisham teaches samples from patients with a variety of diagnoses and representing adult, children, and racial/ethnic minorities can be used (page 178, para. 00707). Grisham teaches some manual processes can be error-prone, introduce cytotoxic reagents, can lose cells, be time-consuming, and require considerable human skill and expertise to generate a uniform sample that has high yield, purity, and viability (page 166, para. 00669). Grisham teaches the DLD chips can be used to replace the centrifugation and resuspension steps and flow cytometry can be used to evaluate recovery (page 180, para. 00710). Grisham teaches leukocytes can be concentrated to ~1 – 10 million cells/mL using the DLD arrays and can be immunostained with fluorescent antibodies against leukocyte differentiation antigens including CD3/4/38 to enumerate the common T lymphocyte subsets(page 168, para. 00680; page 169, para. 00680). Grisham teaches in Table 6 and 7 97% recovery of white blood cells which includes CD3 T cells (page 175 – 176, para. 00697 – 00701). Grisham teaches cells can be labeled with a fluorescent antibody (page 164, para. 00657). Grisham teaches the device can be fluidly connected to a downstream apparatus that permits analysis of particles from an outlet of the device where the apparatus includes a microscope, flow cytometer, HPLC, fluorescence detector, or cell counter (page 164, para. 00660; page 166, para. 00668).
It would have been obvious prior to the effective filing date of the invention as claimed for the person of ordinary skill in the art to combine the teachings of Aurich regarding a method and microfluidic device that separates cells by size and concentrates cells with the teachings of Reichenbach regarding recirculating separated cells with the teachings of Grisham regarding a method for separating and concentrating cells using a microfluidic device with a deterministic lateral display array and channels modified to be non-adherent or repulsive to arrive at the claimed method wherein during the performance of DLD, at least a portion of the target leukocytes is recirculated one or more times so as to replace all or at least a portion of the buffer being applied to the device and wherein the number of times of recirculation is adjusted based on an initial concentration of the target cells and a desired output concentration of the target cells, and where the first outlet comprises a valve to recirculate the target leukocytes to the buffer inlet that is connected to a valve to stop buffer feed and allow recirculation of leukocytes and at least one channel of a flow channel flowing the sample is chemically modified to be non-adherent or repulsive. One would have been motivated to combine the teachings of Aurich, Reichenbach, and Grisham to enrich leukocytes and rare cells that are the size of leukocytes or larger from a blood sample as Aurich teaches isolation and enrichment of rare cells and particles from bodily fluids can be used to understand the concentration, function, and genomic composition of the rare cells and particles and can provide information for diagnosing and treating diseases such as cancer and Aurich teaches given the low concentration of rare cells or particles within biological samples, some form of positive or negative selection or enrichment is needed to detect and/or quantify rare cells or particles and Grisham teaches there is a need for improved methods for chemical and/or enzymatic treatment, washing, and isolation of cells and manual processes can be error-prone. One would have a reasonable expectation of success in combining the teachings as Aurich teaches the concentration of cells before and after concentrating and concentration factors of 1.5 to 15,000-fold can be achieved with the method and device, and Aurich teaches the device can comprise a concentrator with multiple DLD arrays where each array can concentrate particles at different or the same level, and Reichenbach teaches in order to achieve the final particle concentrations desired from the separation process, the particle rich effluent may be re-circulated where it is returned to the entrance of the device by a valving system and Grisham teaches leukocytes can be concentrated to ~1 – 10 million cells/mL using the DLD arrays and Grisham teaches 97% recovery of white blood cells using the method.
13. Claim(s) 2 remains rejected under 35 U.S.C. 103 as being unpatentable over over Aurich (WO2017035262A1; previously cited), hereinafter Aurich which is cited on the IDS filed 03/28/2021, in view of Reichenbach (US20100006479A1; Filed 07/09/2009, Published 01/14/2010; previously cited), hereinafter Reichenbach which is cited on the IDS filed 11/05/2024 in view of Grisham (WO2016019393A1; Filed 03/08/2015; Published 02/04/2016), hereinafter Grisham which is cited on the IDS filed 03/28/2021 as applied to claims 1 and 3 – 18 above, and further in view of Civin (Civin CI, et. al. Cytometry A. 2016 Dec;89(12):1073-1083; previously cited), hereinafter Civin which is cited on the IDS filed 03/28/2021.
Aurich in view of Reichenbach and Grisham make obvious the limitations of claim 1 obvious as set forth above.
Aurich teaches the method for a sample run where a buffer flush is performed after a blood sample is run through the microfluidic array (page 141, 0456) but does not teach “the target cell or target particle product has been recirculated” or “recirculation is stopped” or “wash fluid is again applied”. Grisham teaches areas of potential clogging in the input, middle, and output portions of the array of obstacles in the DLD array following flowing a blood sample through the DLD array (page 13, para. 0051 and 0057; Figure 29A and 35; page 14, para. 0059 – 0060; page 177, para. 00702). Grisham teaches an on-chip cleaning system is activated when a sensor is triggered which can be due to clogging (page 123, para. 00476 – 00478; page 13, para. 0055 – 0056; Figure 33 and 34; page 122, para. 00471 – 00474; page 124; page 172 – 173, para. 00689).
Regarding “the target cell or target particle product has been recirculated” and “recirculation is stopped”, Reichenbach teaches a device comprises a re-circulating flow field that allows at least a portion of the fluid flow to reenter the obstacle field (page 2, 0029). Reichenbach teaches the solution being processed can be re-circulated in a batch or continuous manner and to re-circulate, the solution exiting the device is returned to the beginning of the same device to continue the separation process (page 6, 0060). Reichenbach does not teach “wash fluid is again applied”.
Regarding “wash fluid is again applied to the microfluidic device”, Civin teaches an automated preparation of human leukocytes without centrifugation or manual handling of samples using a microfluidic DLD chip (Abstract). Civin teaches red blood cells remained in the tubing connections to the microchip accounting for small numbers of red blood cells in the product and to generate a microchip product with fewer red blood cells a buffer flush was used and the buffer flush eliminated leukocytes flowing into the waste (page 1082, right col. paragraph 2; page 1077, right col. paragraph 3). Civin teaches the DLD array diverts any rare cells of size equal to or larger than white blood cells into the product (page 1077, right col. paragraph 1). Civin teaches new methods to improve the efficiency of sample preparation in clinical diagnostic testing by flow cytometry is needed (page 1073, paragraph 1). Civin teaches current methods for sample preparation for testing are labor- and time-intensive and may result in a loss of ~10 – 15% of the cells (page 1074, paragraph 1). Civin teaches cell losses during processing necessitate larger starting sample volumes which is an especially critical problem in clinical testing of small children and patients who need many blood tests (page 1073, paragraph 1). Civin teaches the method using the DLD microchip had advantages of short processing time and high leukocyte recoveries (page 1083, left col. paragraph 1).
It would have been obvious prior to the effective filing date of the invention as claimed for the person of ordinary skill in the art to combine the teachings of Aurich regarding a method and microfluidic device that separates cells by size and concentrates cells with the teachings of Reichenbach regarding recirculating separated cells with the teachings of Grisham regarding on-chip cleaning and clogging of the DLD array with the teachings of Civin regarding a buffer flush to arrive at the claimed method wherein after the leukocytes have been recirculated, recirculation is stopped and buffer is again applied to the microfluidic device. One would have been motivated to combine the teachings of Aurich, Reichenbach, Grisham, and Civin to obtain leukocytes free of red blood cells from a blood sample as Grisham teaches the DLD array can be clogged following flowing a blood sample through the DLD array and Civin teaches current methods for sample preparation for testing are labor- and time-intensive and may result in a loss of ~10 – 15% of the cells which necessitate larger starting sample volumes which is an especially critical problem in clinical testing of small children and patients who need many blood tests. One would have a reasonable expectation of success in combining the teachings as Civin teaches a buffer flush eliminated red blood cells in the leukocytes and eliminated leukocytes flowing into the waste.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
14. Claims 1 – 18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 20 of U.S. Patent No. 10844353. Although the claims at issue are not identical, they are not patentably distinct from each other because instant claim 1 is anticipated by patent claim 1.
Patent claim 1 recites a method for preparing central memory T cells from an apheresis or leukapheresis sample, comprising a) purifying the central memory T cells from the sampel by a combination of a Deterministic Lateral Displacement (DLD) step, and in addition to the DLD step, an affinity separation step; and b) expanding the central memory T cells purified in step a) by culturing the central memory T cells in the presence of an activator. Therefore, patent claim 1 is in essence a “species” of the generic invention of instant application claim 1. It has been held that a generic invention is “anticipated” by a “species” within the scope of the generic invention. See In re Goodman, 29 USPQ2d 2010 (Fed. Cir. 1993).
Applicant’s Arguments/ Response to Arguments
15. Applicant Argues: On page 9 – 10, Applicant asserts that Aurich and Reichenbach do not teach or provide motivation for the amendment to claim 1 requiring chemical modification of a channel wall.
Response to Arguments: The previous rejection has been withdrawn in view of the amendment to claim 1. A new rejection is set forth above where Grisham teaches a method for microfluidic processing of blood by deterministic later displacement (DLD) arrays where to reduce non-specific adsorption of cells or compounds, e.g., released by lysed cells or found in biological samples, onto the channel walls, one or more channel walls may be chemically modified to be non-adherent or repulsive (page 130, para. 00507; page 131, para. 00507). Grisham teaches the walls may be coated with a thin film coating of commercial non-stick reagents, such as those used to form hydrogels or fluorinated polymers or heparin can be deposited from solution onto PDMS to make channels hydrophilic while preventing adhesion of blood cells and proteins (page 130, para. 00504 and 00505; page 131, para. 00507). Grisham teaches rinsing the system and tubing with Pluronic F108 surfactant prior to introducing the sample solution (page 188, para. 00748). Grisham teaches surfactants such as Pluronic can be used to make surface protein repellant by adding Pluronic to PDMS formulations during the device fabrication (page 129, para. 00503; page 168, para. 00679). Therefore, Grisham teaches the new limitation of claim 1.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ZANNA M BEHARRY whose telephone number is (571)270-0411. The examiner can normally be reached Monday - Friday 8:45 am - 5:45 pm.
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, Peter Paras can be reached at (571)272-4517. 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.
/Z.M.B./Examiner, Art Unit 1632
/MARCIA S NOBLE/Primary Examiner, Art Unit 1632