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 12 AUGUST 2026 is acknowledged and considered. In the claim set, Claims 1-93, 106 and 108-118 are ‘Canceled’; Claims 94, 95, 98, 99, 100, 101, 102, 104, 119, 120, 121, 122, 123, 124, and 127 are ‘Currently Amended’; Claims 96, 97, 103, 105, 107, 125 and 126 are ‘Previously Amended’.
Current pending claims are Claims 94-105, 107 and 119-127 and are considered on the merits below.
Response to Amendment/Arguments
In the REMARKS filed on 12 AUGUST 2026, Applicant asserts that the combination of Toner and Evans fails to render independent claim 94 obvious because elements 1) – 3) are not taught or suggested in the cited art.
On page 10 of the REMARKS, elements 1) – 3) are : 1) applying a magnetic or electric actuation field to the interior of the flow cell to actuate movement of one or more of the flexible surface-attached structures relative to the attachment sites while flowing the target-containing sample through the chamber of the flow cell, 2) actuation of the one or more of the flexible surface- attached structures prevents or disrupts clogging of the sample material as it flows through the chamber, and 3) actuation of the one or more flexible surface-attached structures increases the probability of the interaction between the target and the at least one of the flexible surface- attached structures.
Examiner respectfully disagrees that the EVANS reference fails to teach or suggest these features/elements.
In Applicant’s own drawings of Figure 13B, 15A and 15B are:
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In the disclosure of the instant invention, Figures 15A and 15B are side views of a micropost and show examples of actuation motion thereof, [0038].
In EVANS, Figures 4(A) and 4(B) and 6, show how linear and rotation actuation strokes of a single nanorod and an angle and vector definition used in deriving the rod bending theory is described.
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As seen in the comparison of Figure 13B, 15A, 15B of the instant invention and Figure 4(A), 4(B) and 6 of EVANS, the actuation and movement of the micropost and rod are the same.
Since the actuation and the actuate movement of the micropost or rod are the same, upon actuation, the elements of 1) – 3) would occur when fluid is flowing through the device.
While the references, in particular the EVANS reference does not specifically mention elements 1) – 3) in the disclosure, [T]he fact that a characteristic is a necessary feature or result of a prior-art embodiment (that is itself sufficiently described and enabled) is enough for inherent anticipation, even if that fact was unknown at the time of the prior invention.”); Abbott Labs v. Geneva Pharms., Inc., 182 F.3d 1315, 1319, 51 USPQ2d 1307, 1310 (Fed. Cir. 1999). And In re Omeprazole Patent Litigation, 483 F.3d 1364, 1373, 82 USPQ2d 1643, 1650 (Fed. Cir. 2007).
EVANS even discloses the magnetic rods to be flexible and even teaches the rod and the rod array become flexible as the diameters decrease.
EVANS discloses “The high-aspect-ratio and low elastic modulus of our PDMS rods lend them a flexibility that makes them ideally suited to serve as actuators… In addition to fabricating these actuating structures, we have developed a theoretical model to predict their bending behavior in a given magnetic field geometry.” The purpose of EVANS is to have bendable (flexible) actuating structures.
EVANS even goes not to observe that as “as the diameter decreases, the rods become very flexible and supercritical drying without substantial rod collapse becomes increasingly difficult.”; Figure 2. In addition, EVANS teaches “we have developed an energy minimization model of a flexible magnetic rod in the presence of a defined magnetic field and field gradient. A model for the energy of a flexible magnetic rod in a homogeneous magnetic field has been proposed by multiple authors.”
The rejection below has been modified to reflect the amendment to the ‘surface-attached structures’.
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 94-105, 107 and 119-127 are rejected under 35 U.S.C. 103 as being unpatentable over TONER, US Patent 8,304,230 B2, submitted on the Information Disclosure Statement on 16 FEBRUARY 2021; US Patents Cite No. 1, in view of EVANS, Magnetically Actuated Nanorod Arrays as Biomimetic Cilia, Nano Letters, 2007, Vol. 7, No. 5, page 1428-1434.
Applicant’s invention is drawn towards a method.
Regarding Claim 94, the reference TONER 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 actuation to the interior of the flow cell to actuate movement while flowing the target-containing sample through the chamber of the flow cell, Column 2 line 66-Column 3 line 8, Column 16 line 14-17, Column 17 line 43-45, wherein the actuation prevents or disrupts clogging of the sample material as it flow through the chamber, Column 18 line 17-22, 55-64;
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.
The TONER reference discloses the claimed invention, but is silent in regards to a flexible surface attached structure and application of a magnetic or electric field to the interior of the flow cell to actuate movement of one or more of the flexible surface-attached structures relative to the attachment sites.
The EVANS reference discloses a method, comprising: providing flexible surface-attached structures disposed in a flow cell, Figure 1 and 2, pages 1429-1430, the flow cell is interpreted to be the space between the PDMS spacers, where fluid flow is to be investigated, page 1430, investigate fluid flow include by actuation of rod array, wherein the flexible surface-attached are attached to an inside surface of the flow cell at a plurality of respective attachment sites, Figure 1 and 2, page 1429, nanorod array are attached to a glass slide / coverslip; applying a magnetic actuation filed to the interior of the flow cell to actuate movement of one or more of the flexible surface-attached structures relative to the attachment sites, Figure 2-6, page 1430, wherein actuation of the one or more of the flexible surface-attached structures is capable to prevent or disrupts clogging of sample material as it flow through the chamber.
EVANS discloses the fabricated nanorod array are to act as biomimetic cilia. It is known in the art that biomimetic cilia are engineered structures designed to mimic the beating motion of natural cilia, which are used by many organisms to move fluids efficiently at microscopic scales.
Therefore, it is expected that the nanorod array that are taught by EVANS would prevent or disrupt clogging when the fluid flow in the space between the PDMS spaces are investigated.
Thus, it would be obvious to one having ordinary skill in the art before the effective filing date to modify the TONER reference to include the nanorod arrays actuated by a magnetic field as taught by EVANS to study the mechanics of nanoscale fluid flow in a ciliated system, to prevent sedimentation of fluids within the fluid cell as well as to prevent or disrupts clogging of sample material as it flow through the chamber.
EVANS reference teaches the flexible rods, but does not specifically mention elements/feature of prevent or disrupts clogging or increase the probability of the interaction of the flexible surface attached structures when actuated, but the, [T]he fact that a characteristic is a necessary feature or result of a prior-art embodiment (that is itself sufficiently described and enabled) is enough for inherent anticipation, even if that fact was unknown at the time of the prior invention.”); Abbott Labs v. Geneva Pharms., Inc., 182 F.3d 1315, 1319, 51 USPQ2d 1307, 1310 (Fed. Cir. 1999). And In re Omeprazole Patent Litigation, 483 F.3d 1364, 1373, 82 USPQ2d 1643, 1650 (Fed. Cir. 2007).
EVANS even discloses the magnetic rods to be flexible and even teaches the rod and the rod array become flexible as the diameters decrease.
EVANS discloses “The high-aspect-ratio and low elastic modulus of our PDMS rods lend them a flexibility that makes them ideally suited to serve as actuators… In addition to fabricating these actuating structures, we have developed a theoretical model to predict their bending behavior in a given magnetic field geometry.” The purpose of EVANS to have bendable (flexible) actuating structures.
EVANS even goes not to observe that as “as the diameter decreases, the rods become very flexible and supercritical drying without substantial rod collapse becomes increasingly difficult.”; Figure 2. In addition, EVANS teaches “we have developed an energy minimization model of a flexible magnetic rod in the presence of a defined magnetic field and field gradient. A model for the energy of a flexible magnetic rod in a homogeneous magnetic field has been proposed by multiple authors.”
Additional Disclosures Included by the combination 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 flexible 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 flexible 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 flexible 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 flexible surface-attached structures in a reciprocating manner to increase a time- averaged cross-section of the flexible surface-attached structures, TONER Column 14 line 10-44, EVANS Figure 4-6 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 flexible 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 flexible surface-attached structures, EVANS Figure 4-6, page 1430-1432.; 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 flexible surface- attached structures and the bottom inside surface, TONER Figure 8, Column 11 line 7-37; and the flexible 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 flexible surface- attached structures and the bottom inside surface and is below the flexible 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 flexible surface- attached structures, EVANS, Figure 3-6, page 1430-1432; comprising moving the flexible surface- attached structures at a speed or frequency configured for causing an effect, EVANS page 1430, selected from the group consisting of: adjusting or varying an inter- structure spacing between the flexible surface-attached structures, EVANS page 1429, rod array diameter can be from 200 nm to 1 micrometer; preventing or disrupting clogging of sample material between the flexible surface- attached structures; preventing or disrupting non-specific binding of sample material on the flexible surface- attached structures; and a combination of two or more of the foregoing, EVANS discloses the fabricated nanorod array are to act as biomimetic cilia. It is known in the art that biomimetic cilia are engineered structures designed to mimic the beating motion of natural cilia, which are used by many organisms to move fluids efficiently at microscopic scales.; 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 flexible surface-attached structures are oriented substantially along a direction normal to the inside surface of the flow cell at which are the flexible 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 flexible surface-attached structures attached, EVANS Figure 1, 2, 5, page 1429 .; 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 flexible surface-attached structures moving with a side-to-side two-dimensional motion; the flexible surface-attached structures moving with a circular motion; the flexible surface-attached structures moving in a tilted motion relative to the inside surface of the flow cell to which the flexible surface-attached structures are attached; or a combination or two or more of the foregoing, EVANS Figure 4-6 , page 1430.; and Claim 121: wherein the method of claim 94, wherein a property of a fluid in an interior, a property of the flexible 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, EVANS, Figure 4-6, page 1430-1431.; 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, EVANS, Figure 3, page 1430.; 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 flexible surface-attached structures.; and Claim 124: wherein the method of claim 94, the actuation of the one or more flexible surface- attached structures causes the targets of the target-containing sample to at least mix or circulate within the flow cell, EVANS discloses the fabricated nanorod array are to act as biomimetic cilia. It is known in the art that biomimetic cilia are engineered structures designed to mimic the beating motion of natural cilia, which are used by many organisms to move fluids efficiently at microscopic scales.; 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. ; Claim 126: wherein the flow cell is coupled to a fluidic circuit configured to establish a flow of fluid, TONER Figure 7, Column 11 line 7-18, pump, tubing, syringe etc. ; and Claim 127: wherein the method of claim 94, wherein the flexible surface-attached structures are positioned in a fluid flow path between the fluid inlet and the fluid outlet such that the target-containing sample flowing through the flow cell comes into contact with the surface-attached structures, TONER Column 12 59 – Column 13 line 16.
Applicant’s invention is drawn towards a method.
Regarding Claim 104, the reference TONER 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 flexible 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 flexible 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 on the flexible surface-attached structures, Column 2 line 37-39, or on the inside surface of the flow cell, or on both the flexible surface-attached structures and the inside surface, wherein applying the actuation increase the probability of an interaction between the target and at least one flexible surface-attached structures, Column 2 line 66-Column 3 line 8, Column 16 line 14-19; and
wherein capturing the target produces a depleted sample containing a reduced concentration of the target, and wherein the interaction comprises binding or capturing the target to 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.
The TONER reference discloses the claimed invention but is silent regarding application of a magnetic or electric 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.
The EVANS reference discloses a method, comprising: providing flexible surface-attached structures disposed in a flow cell, Figure 1 and 2, pages 1429-1430, the flow cell is interpreted to be the space between the PDMS spacers, where fluid flow is to be investigated, page 1430, investigate fluid flow include by actuation of rod array, wherein the flexible surface-attached are attached to an inside surface of the flow cell at a plurality of respective attachment sites, Figure 1 and 2, page 1429, nanorod array are attached to a glass slide / coverslip; and the flexible surface – attached structures are movable in an interior of the flow cell relative to the attachment sites in response to applying a magnetic actuation, Figure 3-6, page 1429-1431.
Thus, it would be obvious to one having ordinary skill in the art before the effective filing date to modify the TONER reference to include the nanorod arrays actuated by a magnetic field as taught by EVANS to study the mechanics of nanoscale fluid flow in a ciliated system, increase movement of the structure to increase contact with fluid in the flow cell to prevent sedimentation of fluids within the fluid cell as well as to prevent or disrupts clogging of sample material as it flow through the chamber.
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
THIS ACTION IS MADE FINAL. 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
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