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 .
Status of Claims
The claim set submitted on 17 SEPTEMBER 2025 is acknowledged and considered. In the claim set, Claims 1-93, 106, 108-118 are ‘Cancelled’; Claims 94, 101, 119, 123 and 125 are ‘Currently Amended’; Claims 95-100, 102-105, 107, 120-122, and 124 are ‘Previously Presented’ or ‘Previously Amended’.
Current pending claims are Claims 94-105, 107, 119-125 and are considered on the merits below.
Response to Amendment/Arguments
Applicant’s arguments, see REMARKS, filed 17 SEPTEMBER 2025, with respect to the 112(b) rejection have been fully considered and are persuasive. The 112(b) rejections have been withdrawn.
Applicant’s arguments with respect to claims 94-105, 107 and 119-125 have been considered and the grounds of rejection for the pending claims are modified compared to the previous action due to the amendments but rely on the same prior art and further in view of JUDITH, cited on the PTO-892 and are attached with this Office Action.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 17 APRIL 2025 was filed on the mailing date of the Non-Final Office Action on 17 APRIL 2025. 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 94-103, 107, 119-125 are rejected under 35 U.S.C. 103 as being unpatentable over SUPERFINE, US Patent 8,586,368 B1, in view of TONER, US Patent 8,304,230 B2, submitted on the Information Disclosure Statement on 16 FEBRUARY 2021; US Patents Cite No. 1, and further in view of JUDITH, Micro-elastometry on whole blood clots using actuated surface-attached posts (ASAPs), Lab Chip, 2015, 15, 1385.
Applicant’s invention is drawn towards a method.
Regarding Claim 94, the reference SUPERFINE discloses a method, abstract, Column 4 line 34-52, the method comprising: subjecting a target-containing sample in a flow cell comprising a fluid inlet and a fluid outlet and a chamber, Figure 8B, and to contact with surface- attached structures disposed in the flow cell, Column 4 line 34-52, biofluid specimen placed in a well, wherein the surface- attached structures are attached to an inside surface of the flow cell at a plurality of respective attachment sites, Column 4 line 23-52, microposts array, Figure 7B; applying a magnetic or electric actuation field to the interior of the flow cell to actuate one or more of the surface- attached structures relative to the attachment sites while a target-containing sample is in the chamber of the flow cell, wherein the actuation of the one or more of the surface- attached structures prevents or disrupts clogging of the sample material as it flows through the chamber , Figure 7B and 11, Column 4 line 34-52, ‘actuation force’ is force applied to the microposts, wherein actuation of the one or more surface-attached structures increases the probability of the interaction between a target-containing sample and the at least one surface-attached structures, Column 4 line 34-59, as actuation force is applied microposts exhibit motion, therefore interacting with the sample more.
The SUPERFINE reference discloses the claimed invention, but is silent in regards to wherein the method is for extracting a target from a sample, while flowing a target-containing sample through a flow cell and , isolating targets of the target-containing sample from a remaining portion of the sample through an interaction between the target and the at least one of the surface -attached structures.
The TONER reference discloses a method for extracting a target from a sample, abstract, separating cells from a sample, the method comprising: flowing a target-containing sample through a flow cell comprising a fluid inlet and a fluid outlet and a chamber therebetween, and into contact with surface- attached structures disposed in the chamber of the flow cell, Figure 7, 8 and 17, Column 11 line 9-37, perfuse a mixture of cells through microfluidic device though inlet, Column 13 line 17-34, inlet for accepting blood / outlet for collection microfluidic device includes obstacles through flow chamber, wherein the surface- attached structures are attached to an inside surface of the flow cell at a plurality of respective attachment sites, Figure 8, Column 11 line 14-37, obstacles are in ordered array or randomly through flow chamber; applying a magnetic or electric actuation field to the interior of the flow cell to actuate movement while flowing the target-containing sample through the chamber of the flow cell, Column 17 line 43-45, wherein the actuation prevents or disrupts clogging of the sample material as it flow through the chamber; and isolating the target of the target-containing sample from a remaining portion of the sample through an interaction between the target and the at least one of the surface -attached structures, Column 17 line 43-45, Column 2 line 59-63, Column 10 line 56-65, and wherein the interaction comprises binding or capturing the target to at least one of the surface-attached structures, Claims 8, 9, 15, 16, selective binding, Column 2 line 38-39, 59-61, Column 3 line 38-51, Column 11 line 24-37, Column 15 line 22-26 and Column 16 line 3-6, capture of specific population of cells expressing certain surface model.
It would be obvious to one having ordinary skill in the art before the effective filing date to modify the claimed invention of SUPERFINE to have the method to extracting a target from a sample, while flowing a and target-containing sample through a flow cell such that the interaction comprises binding or capturing the target as suggested by TONER, so that the output can be collected separately for downstream process, Column 8 line 35-37, or further analysis or processing, TONER Column 10 line 56-65, and to isolate the target of the target-containing sample from a remaining portion of the sample through an interaction between the target and the at least one of the surface -attached structures as taught by TONER for employing positive selection or negative selection, TONER Column 10 line 56-65.
The combination above suggests the claimed invention, but is silent in regards to the magnetic actuation field to the interior of the flow cell actuates movement of the surface attached structures.
The JUDITH reference discloses a method , abstract, page 1385, Introduction, page 1388, ASAP control and analysis, the method comprising:
flowing a target-containing sample through a flow cell comprising a fluid inlet and a fluid outlet and a chamber therebetween and into contact with surface- attached structures disposed in the chamber of the flow cell, page 1387, Figure 2, page 1386-1387, ASAP manufacturing, Experimental setup, Blood sample preparation, wherein the surface- attached structures are attached to an inside surface of the flow cell at a plurality of respective attachment sites, page 1386, Figure 1, ASAP manufacturing, Experimental setup;
applying a magnetic or electric actuation field to the interior of the flow cell to actuate movement of one or more of the surface- attached structures relative to the attachment sites while flowing the target-containing sample through the chamber of the flow cell, page 1387, Figure 2 and 3, Blood sample preparation, page 1388, ASAP control and analysis, magnetic field turned on/off, wherein the actuation of the one or more of the surface- attached structures prevents or disrupts clogging of the sample material as it flows through the chamber, page 1388, ASAP control and analysis, page 1389-1390, Demonstration of ASAP as VHA, posts deform the clot; and
isolating the target of the target-containing sample from a remaining portion of the target- containing sample through an interaction between the target and at least one of the surface- attached structures, page 1392, Application of ASAP technology, wherein actuation of the one or more surface- attached structures increases the probability of the interaction between the target and the at least one of the surface- attached structures, page 1388, ASAP control and analysis, and wherein the interaction comprises binding or capturing the target to at least one of the surface- attached structures, page 1388-1389, ASAP control and analysis, Results.
It would be obvious to one having ordinary skill in the art before the effective filing date to modify the combination above to include the step of applying a magnetic or electric actuation field to the interior of the flow cell to actuate movement of one or more of the surface- attached structures relative to the attachment sites while flowing the target-containing sample through the chamber of the flow cell as taught by JUDITH to not only prevent clogging, but also to observe the posts response to the applied magnetic field as it relate a blood clot forming and to determine the clot stiffness with commercial thromboelastograph, abstract.
Additional Disclosures Included are: Claim 95: wherein the method of claim 94, wherein isolating the target comprises binding the target to a binding agent disposed in the flow cell; wherein the binding agent is selected from the group consisting of: a binding agent disposed on or integrated with an outer surface of at least some of the surface-attached structures; a binding agent disposed on or integrated with the inside surface; and both of the foregoing, TONER, Column 15 line 12-36, Column 16 line 3-19.; Claim 96: wherein the method of claim 95, wherein isolating target comprises releasing the target after binding, such that the released target are flowable out from the flow cell; wherein releasing is selected from the group consisting of: flowing a release agent through the flow cell and into contact with the target bound to the binding agent disposed in the flow cell, TONER Column 17 line 40-43, Column 16 line 16-19; irradiating the bound target with photons under conditions configured for inducing photolysis; applying a shear force to the bound target at a magnitude configured for unbinding the bound targets; and a combination of two or more of the foregoing, TONER, Column 2 line 66-67, Column 16 line 3-19, Column 17, line 1-51.; Claim 97: wherein the method of claim 95, wherein isolating target comprises, releasing the target after binding, such that the released target are flowable out from the flow cell, TONER Column 16 line 3-19, Figure 8, 21, wherein releasing comprises flowing a release agent through the flow cell and into contact with the bound target, and the release agent is selected from the group consisting of: a chemical lysing agent; a pH cell lysing agent; an enzymatic liquefaction agent; and a solvent, TONER Column 16 line 3-19.; Claim 98: wherein the method of claim 95, wherein isolating the target comprises, releasing the target after binding, such that the released target are flowable out from the flow cell, TONER Column 16 line 3-19, Figure 8, 21, collection reservoir; wherein releasing comprises applying a shear force to the bound target at a magnitude configured for unbinding the bound targets, and applying the shear force, TONER Column 16 line 3-19, Figure 8, 21, is selected from the group consisting of: flowing a liquid through the flow cell at a flow rate configured for releasing the bound targets by shearing, TONER Column 16 line 3-19, Figure 8, 21, increased flow rate, that is higher shear force; applying a magnetic or electric field to the flow cell to actuate movement of the surface- attached structures at a speed configured for releasing the bound target by shearing; both of the foregoing.; Claim 99: wherein the method of claim 94, wherein a binding agent is disposed on or integrated with an outer surface of at least some of the surface-attached structures, and further comprising, while flowing the target-containing sample, applying a magnetic or electric field to the flow cell to actuate movement of the surface-attached structures in a reciprocating manner to increase a time- averaged cross-section of the surface-attached structures, SUPERFINE Column 2 line 25-34, Column 4 line 34-53, actuation force may include magnetic, or electric force.; Claim 100: wherein the method of claim 94, wherein isolating target comprises trapping the target by preventing the target from passing between neighboring surface-attached structures; and after trapping, TONER Column 11 line 38-Column 12 line 48, Column 17 line 28-45, releasing the target by applying a magnetic or electric field to the flow cell to actuate movement of the surface-attached structures, SUPERFINE Column 4 line 34-52.; Claim 101: wherein the method of claim 94, wherein isolating the target comprises separating the target from non-targets of the target-containing sample by size or density, such that the target and the non-targets elute from the flow cell at different times, TONER Column 17 line 52-Column 18 line 15, sized based separation based on sieves that selectively allow passage of particles based on their size, shape or deformability; wherein: the target has a different size than the non-targets, TONER Column 17 line 52-Column 18 line 15; the inside surface is a top inside surface of the flow cell, TONER Figure 7 and 8, and the flow cell further comprises a bottom inside surface spaced from the top inside surface such that a structure-free region is between the surface- attached structures and the bottom inside surface, TONER Figure 8, Column 11 line 7-37; and the surface-attached structures are positioned with an inter- structure configured spacing effective for forcing either the target or the non-targets, whichever are larger, to flow substantially only through the structure-free region, TONER Figure 8, Column 11 line 7-37; or wherein: the target have a different density than the non-targets, TONER Column 17 line 52-Column 18 line 15; and the bottom inside surface is spaced from the top inside surface such that the structure-free region is between the surface- attached structures and the bottom inside surface and is below the surface- attached structures, TONER Figure 8, Column 11 line 7-37; and flowing the target-containing sample through the flow cell is done at a flow rate configured for allowing a majority of either the target or the non-targets, whichever are denser, to diffuse into the structure- free region and toward the bottom inside surface, TONER Column 15 line 12-37, Column 17 line 52-Column 18 line 15.; Claim 102: wherein the method of claim 94, comprising, while flowing the target-containing sample, applying a magnetic or electric field to the flow cell to actuate movement of the surface- attached structures, SUPERFINE Column 4 line 45-52, Column 5 line 27-60, magnetic or electric force actuation, Column 14, line 21-29; comprising moving the surface- attached structures at a speed or frequency configured for causing an effect, SUPERFINE Column 4 line 34-44, selected from the group consisting of: adjusting or varying an inter- structure spacing between the surface-attached structures, SUPERFINE Column 9 line 14-33; preventing or disrupting clogging of sample material between the surface- attached structures; preventing or disrupting non-specific binding of sample material on the surface- attached structures; and a combination of two or more of the foregoing.; Claim 103: wherein the method of any of claim 94, comprising, after isolating the target, transferring the target to an analytical instrument, and operating the analytical instrument to measure an attribute of the target, TONER Column 17 line 28-51.; Claim 107: wherein the method for extracting a target from a sample of claim 94, wherein the target is a non-analyte target comprising an interferent, suppressant, and/or element contributing only to background signal, and wherein the non-analyte target is isolated from the target-containing sample to purge the target-containing sample of the non-analyte target and/or to analyze the target-containing sample in the absence of the non-analyte target, TONER Column 10 line 55-65, surfaces contain specific substances that bind to certain subpopulation, Column 15 line 12-36, non-cellular matter, such as non-biological matter (e.g., beads), non-viable cellular debris (e.g., membrane fragments).; Claim 119: wherein the method of claim 94, wherein the surface-attached structures are oriented substantially along a direction normal to the inside surface of the flow cell at which are the surface- attached structures attached, or are oriented at an angle with respect to the direction normal to the inside surface of the flow cell at which are the surface-attached structures attached, SUPERFINE Figure 1C (5), Column 4 line 19-59, Column 8 line 10-36, JUDITH Figure 1, page 1386, ASAP manufacturing .; Claim 120: wherein the method of claim 94, wherein the surface- attached structures when actuated move in a movement pattern selected from the group consisting of: the surface-attached structures moving with a side-to-side two-dimensional motion; the surface-attached structures moving with a circular motion; the surface-attached structures moving in a tilted motion relative to the inside surface of the flow cell to which the surface-attached structures are attached; or a combination or two or more of the foregoing, SUPERFINE Column 4 line 45-52, Column 6 line 30-48, amplitude and phase of micropost motion reads on surface-attached structures moving with a side-to-side two-dimensional motion, JUIDTH, Figure 3 and 4, page 1388, ASAP control and analysis; and Claim 121: wherein the method of claim 94, wherein a property of a fluid in an interior, a property of the surface-attached structures, or a property of binding agent in the interior of the flow cell is measured while flowing the target-containing sample through the flow cell, SUPERFINE, Claim 14, Figure 11, character 1108, Column 4 line 60-Column 5 line 14.; Claim 122: wherein the method of claim 94, wherein the magnetic or electric actuation force for actuating the one or more of the surface- attached structures is applied by a driver, SUPERFINE Column 2 line 29, JUDITH, Figure 2.; Claim 123: wherein the method of claim 94, wherein the binding or capturing comprises one or more of a physical, TONER Column 3 line 1-2, Column 5 line 34-37, size or shape or deformability, chemical, TONER Column 5 line 34-37, cell binding, or molecular interaction, TONER Column 5 line 34-37, cell binding, between the target and the at least one the surface-attached structures, JUDITH page 1388 , ASAP Control and Analysis, Results.; and Claim 124: wherein the method of claim 94, the actuation of the one or more surface- attached structures causes the targets of the target-containing sample to at least mix or circulate within the flow cell, SUPERFINE, Column 4 line 34-52, actuation compels microposts to exhibit motion, therefore moving fluid or circulate within the well, JUDITH, page 1388, ASAP control and analysis, Figure 3 and 4.; and Claim 125: wherein the method of claim 94, wherein the sample has a volume of greater than or equal to 10 mL, TONER Column 7 line 24-30, Column 10 line 5-10, line 32-36.
Claims 104-105 are rejected under 35 U.S.C. 103 as being unpatentable over SUPERFINE, US Patent 8,586,368 B1, and further in view of TONER, US Patent 8,304,230 B2, submitted on the Information Disclosure Statement on 16 FEBRUARY 2021; US Patents Cite No. 1.
Applicant’s invention is drawn towards a method.
Regarding Claim 104, the reference SUPERFINE discloses a method, abstract, Column 4 line 34-52, the method comprising: flowing a target-containing sample into a flow cell and into contact with surface- attached structures disposed in the flow cell, Column 4 line 34-52, biofluid specimen placed in a well, wherein the surface- attached structures are attached to an inside surface of the flow cell at a plurality of respective attachment sites, Column 4 line 23-52, microposts array, Figure 7B, and the surface- attached structures are movable in an interior of the flow cell relative to the attachment sites in response to applying a magnetic or electric actuation, Figure 7B and 11, Column 4 line 34-52, Column 17 line 43-45, ‘actuation force’ is force applied to the microposts, wherein applying the magnetic or electrical actuation increases the probability of the interaction between a target and the at least one surface-attached structures or the inside surface of the flow cell, Column 4 line 34-59, as actuation force is applied microposts exhibit motion, therefore interacting with the target containing sample more.
The SUPERFINE reference discloses the claimed invention, but is silent in regards to wherein the method is for extracting a target from a sample, while flowing a target-containing sample through a flow cell and capturing the target on the surface-attached structures, on or the inside surface of the flow cell, or on both the surface-attached structures and the inside surface.
The TONER reference discloses a method for extracting a target from a sample, abstract, separating cells from a sample, the method comprising: flowing a target-containing sample through a flow cell and into contact with surface- attached structures disposed in the flow cell, Figure 7, 8 and 17, Column 11 line 9-37, perfuse a mixture of cells through microfluidic device though inlet, Column 13 line 17-34, inlet for accepting blood / outlet for collection microfluidic device includes obstacles through flow chamber, wherein the surface- attached structures are attached to an inside surface of the flow cell at a plurality of respective attachment sites, Figure 8, Column 11 line 14-37, obstacles are in ordered array or randomly through flow chamber; and capturing the target[[s]] on the surface-attached structures, or on the inside surface of the flow cell, or on both the surface-attached structures and the inside surface, Column 15 line 64-Column 16 line 2, Figure 20, and wherein capturing the target produces a depleted sample containing a reduced concentration of the target, Column 10 line 56-65, and wherein the interaction comprises binding or capturing the target to at least one of the surface-attached structures, Claims 8, 9, 15, 16, selective binding, Column 2 line 38-39, 59-61, Column 3 line 38-51, Column 11 line 24-37, Column 15 line 22-26 and Column 16 line 3-6, capture of specific population of cells expressing certain surface model.
It would be obvious to one having ordinary skill in the art before the effective filing date to modify the claimed invention of SUPERFINE to have the method to extracting a target from a sample, while flowing a target-containing sample through a flow cell as suggested by TONER, so that the output can be collected separately for downstream process, Column 8 line 35-37, or further analysis or processing, TONER Column 10 line 56-65, and capturing produces a depleted sample containing a reduced concentration of the targets through the device as taught by TONER to isolate rare cells or target cells, Column 15 line 55-56, or to obtain a differential distribution of targets or various population in sample such as blood, Column 15 line 56-57, as well as employing positive selection or negative selection, TONER Column 10 line 56-65.
Additional Disclosures Included is : Claim 105: wherein the method of claim 104, comprising outputting the depleted sample from the flow cell, wherein the captured target remain captured in the flow cell, and releasing the captured target and outputting the released target from the flow cell, TONER Figure 21, outlet for depleted sample and collection reservoir for further analysis after release/removal, Column 10 line 56-65.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTINE T MUI whose telephone number is (571)270-3243. The examiner can normally be reached M-Th 5:30 -15:30 EST.
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CTM
/CHRISTINE T MUI/Primary Examiner, Art Unit 1797