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 .
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.
1. Claims 1, 2, 5, 6, 13, 16, 19, 21, 24-26, 28, 32-34, 36, 38, 40, 63 and 64 are rejected under 35 U.S.C. 103 as being unpatentable over International Patent Application Publication No. WO2018226891 to Kelso et al. ‘891 (“Kelso et al. ‘891”) (cited by applicant) in view of U.S. Patent Application Publication No. 2017/0073667 to Ohashi et al. (cited by applicant) and U.S. Patent Application Publication No. 2017/0284922 to Mermod et al.
Kelso et al. ‘891 teaches devices that facilitate the magnetic separation of an analyte from a sample, and methods of use thereof. (page 1, lines 7-10)
The methods include contacting a sample with a population of paramagnetic particles (PMPs) in an aqueous phase in a first region of a sample processing cartridge (trans-interface magnetic separation (TIMS) cartridge) that comprises multiple (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, or more, or ranges therebetween (e.g., 2 or more)) discrete chambers. (page 16, lines 33-34)
In some embodiments, reagents (e.g., lysing reagents, binding reagents, elution reagents, washing reagents, etc.) are added or preloaded in the chambers. (page 17, lines 5-6)
The PMPs include capture reagents (e.g., nucleic acid hybridization probes, antibodies or antibody fragments, affinity agents (e.g., streptavidin, divalent nickel, etc.), etc.) for a desired analyte (e.g., DNA or RNA, agent displaying an epitope, affinity target (e.g., linked to biotin, displaying a His6 tag, etc.) etc.) are added by a user or pre-loaded into a chamber. (page 17, lines 6-10)
The PMPs are transported from an aqueous phase in the first region to an air phase in a second region of the cartridge by applying a magnetic force to the magnetic particles (see Fig. 2 for an air phase (air gap) in a second region of the cartridge. (page 17, In 17-22)
Kelso et al. ‘891 teaches that some embodiments herein make use of an air gap (e.g., comprising one or more liquid/air interfaces) between two chambers to facilitate the transfer of PMPs/binding agents and analytes bound thereto from an initial chamber to a subsequent chamber while minimizing transfer of liquid (e.g., sample, reagents, contaminants, buffer, etc.). (page 17, lines 19-22)
Kelso et al. ‘891 teaches that in some embodiments a magnet is placed (e.g., manually by a user, by an automated device, etc.) on the distal side of the transfer surface to form a pellet of analyte-bound PMPs against the transfer surface. Movement of the magnetic field, laterally across the transfer surface, moves the collected PMPs through the pinned liquid of the first chamber, into the air gap between the first and second chambers). (page 18, lines 16-20)
Kelso et al. ‘891 does not teach a first population of magnetic particles and a second population of magnetic particles in an aqueous phase, wherein the magnetic particles in the second population are at least two-times larger in size than the magnetic particles in first population.
Ohashi et al. teaches a magnetic particle manipulation method and discloses a first population of magnetic particles (71) and a second population of magnetic particles (60) in an aqueous phase (32), wherein the magnetic particles (60) have a larger particle diameter than magnetic particles (71) and are moved along together by magnetic field manipulation. (Fig. 1A-1D;[0018])
The magnet particles 71 and the magnet solid 60 passed through a liquid medium layer 21 move from the liquid medium layer 21 to the second liquid layer 32 by magnetic field manipulation. [0042]
The particle diameter of the magnetic particles (71) is preferable in the range of 0.1-20 µm and more preferably in the range of 0.5-10 µm. [0049] and the particle diameter of the magnetic solid (60) is preferably at least 50 µm, more preferably at least 100 µm and most preferably at least 150 µm (at least two times larger). [0055]
The magnetic particles (71) are moved along with the magnetic solid (60) by the magnet field. (Abstract)
Kelso et al. ‘891 teaches that a plurality of magnetic solids (60) can be used. [0064]
It would have been obvious to a person of ordinary skill in the art at the time of the invention to modify Kelso et al. ‘891 to have a first population of magnetic particles and a second population of magnetic particles in an aqueous phase and the magnetic particles in the second population are at least two-times larger in size than the magnetic particles in first population as taught by Ohashi et al. for purposes of eliminating a mal-effect relative to the background and the foreign materials as taught by Ohashi et al. [0006]
In response to claim 1 having been amended to recite that the second population of magnetic particles is incapable of associating with the target analyte (but not that the target analyte comprises nucleic acids as still recited in claim 24), Mermod et al. teaches the use of both functional magnetic particles (capture beads) and non-functional magnetic particles (carrier beads). [0110], [0167]
It would have been obvious to one of ordinary skill in the art before applicant’s effective filing date to modify Kelso et al. in view of Ohashi et al. to use functionalized magnetic particles to capture target analytes and non-functionalized magnetic particles for the magnetic solids of Kelso et al. to capture target analytes with the functionalized magnetic particles as taught by Mermod et al. and use the non-functionalized magnetic particles to collect, by aggregation, the functionalized magnetic particles with the target analytes trapped thereon.
I.) Regarding applicant’s claim 1, as noted above Kelso et al. in view of Ohashi et al. and Mermod et al. teaches all the elements of claim 1.
Therefore, Kelso et al. ‘891 in view of Ohashi et al. and Mermod et al. renders claim 1 obvious.
II.) Regarding applicant’s claim 2, as noted above, Kelso et al. ‘891 in view of Ohashi and Mermod et al. renders claim 1 obvious from which claim 2 depends.
Claim 2 recites that the magnetic particles in the first population have a diameter of 500nm-10 µm.
As noted above, Ohashi et al. teaches that particle diameter of the magnetic particles (71) is preferable in the range of 0.1-20 µm and more preferably in the range of 0.5-10 µm.
Therefore, Kelso et al. ‘891 in view of Ohashi et al. and Mermod et al. renders claim 2 obvious.
III.) Regarding applicant’s claim 5, as noted above, Kelso et al. ‘891 in view of Ohashi renders claim 1 obvious from which claim 5 depends.
Claim 5 recites applying the magnetic force causes the magnetic particles to aggregate in an area in the first region, which area is adjacent to the source of the magnetic force and wherein the transporting comprises maintaining the magnetic force on the aggregated magnetic particles, moving the aggregated magnetic particles to the air phase in the second region of the cartridge, and the method further comprises moving the aggregated magnetic particles to an aqueous phase in a third region of the cartridge.
As noted above Kelso et al. ‘891 teaches three or more regions in the cartridge through which magnetic particles are transferred via air phases.
Ohashi et al. teaches that the magnetic particles are aggregated by the magnetic force. [0041]
In Kelso et al. ‘891 in view of Ohashi et al. and Mermod et al. it would be obvious that the magnetic force used to move the magnetic particles would aggregate the magnetic particles as they are transferred between three or more regions via air phases.
Therefore, Kelso et al. ‘891 in view of Ohashi et al. and Mermod et al. renders claim 5 obvious.
IV.) Regarding applicant’s claim 6, as noted above, Kelso et al. ‘891 in view of Ohashi and Mermod et al. renders claim 1 obvious from which claim 6 depends.
Claim 6 recites that transporting the first and second populations of magnetic particles comprises moving a magnet generating the magnetic force relative to the different regions of the cartridge or moving the cartridge or a portion thereof relative to a magnet generating the magnetic force.
As noted above, both Kelso et al. ‘891 and Ohashi et al. teach providing a magnetic field to move magnetic particles.
Therefore, Kelso et al. ‘891 in view of Ohashi et al. and Mermod et al. renders claim 6 obvious.
V.) Regarding applicant’s claim 13, as noted above, Kelso et al. ‘891 in view of Ohashi renders claim 1 obvious from which claim 13 depends.
Claim 13 recites that the first region is a first chamber that comprises the aqueous phase and the second region is a second chamber that comprises the air phase and wherein the first and second chambers are connected via a first channel, wherein a difference in pressure between the first and second chambers establishes a liquid-air interface in the first channel.
Kelso et al. ‘891 teaches air pressure differences that provide air gaps that are shown in Fig. 2. (page 10, lines 23-24)
While Kelso et al. ‘891 teaches air gaps through which magnetic particles are transferred, Kelso et al. ‘891 in view of Ohashi et al. and Mermod et al. does not teach air phase chamber between first and second chambers.
It would have been obvious to one of ordinary skill in the art to provide an air phase chamber between first and second chambers in Kelso et al. ‘891 in view of Ohashi et al. and Mermod et al. for purposes of assuring collection of all the magnetic particles in such air phase chamber before transferring into the second chamber. Clearly passing the magnetic particles through an area that contains air does not adversely impact the teachings of Kelso et al. ‘891 inasmuch as Kelso et al. ‘891 transfers the magnetic particles through the air gaps.
Therefore, Kelso et al. ‘891 in view of Ohashi et al. and Mermod et al. renders claim 13 obvious.
VI.) Regarding applicant’s claim 16, as noted above, Kelso et al. ‘891 in view of Ohashi and Mermod et al. renders claim 1 obvious from which claim 16 depends.
Claim 16 recites transporting the first and second populations of magnetic particles from the air phase in the second region to an aqueous phase in a separate cartridge, wherein the transporting comprises maintaining a magnetic force on the magnetic particles till the second region is in association with the aqueous phase in the separate cartridge and removing the magnetic force, thereby allowing the magnetic particles to be released into the aqueous phase.
Kelso et al. ‘891 in view of Ohashi et al. and Mermod et al. does not teach transporting the first and second populations of magnetic particles from the air phase in the second region to an aqueous phase in a separate cartridge, wherein the transporting comprises maintaining a magnetic force on the magnetic particles till the second region is in association with the aqueous phase in the separate cartridge and removing the magnetic force, thereby allowing the magnetic particles to be released into the aqueous phase.
It would have been obvious to one of ordinary skill in the art to use two or more cartridges in Kelso et al. ‘891 in view of Ohashi et al. Mermod et al. and transfer the magnetic particles between different cartridges for purpose of being able to combine cartridges that have different numbers of chambers for the chemistry taught by Kelso et al. ‘891. Note, that mere duplication of parts has no patentable significance unless a new and unexpected result is produced. (MPEP 2144.04(VI)(B))
Therefore, Kelso et al. ‘891 in view of Ohashi et al. and Mermod et al. renders claim 16 obvious.
VII.) Regarding applicant’s claim 19, as noted above, Kelso et al. ‘891 in view of Ohashi and Mermod et al. renders claim 1 obvious from which claim 19 depends.
Claim 19 recites the contacting comprises contacting a lysis buffer comprising the first and second populations of magnetic particles with the sample or wherein the contacting comprises placing the sample in the first region followed by introducing into the first region the first and second populations of magnetic particles.
Kelso et al. ‘891 teaches providing a lysis buffer in the first chamber. (page 3, lines 21-22)
Therefore, Kelso et al. ‘891 in view of Ohashi et al. and Mermod et al. renders claim 19 obvious.
VIII.) Regarding applicant’s claim 21, as noted above, Kelso et al. ‘891 in view of Ohashi and Mermod et al. renders claim 1 obvious from which claim 21 depends.
Claim 21 recites that the target analyte comprises a cell, a virus, a protein, a nucleic acid, or a nucleic acid released from disruption of a cell or a virus.
Kelso et al. ‘891 teaches that the biological sample can include cells. (page 3, lines 20-21)
Therefore, Kelso et al. ‘891 in view of Ohashi et al. and Mermod et al. renders claim 21 obvious.
IX.) Regarding applicant’s claim 24, as noted above, Kelso et al. ‘891 in view of Ohashi and Mermod et al. renders claim 1 obvious from which claim 24 depends.
Claim 24 recites that the target analyte comprises nucleic acids.
Kelso et al. ‘891 (page 2, lines 19-30) and Ohashi et al. [0006] each teach nucleic acids as targets.
Therefore, Kelso et al. ‘891 in view of Ohashi et al. and Mermod et al. renders claim 24 obvious.
X.) Regarding applicant’s claim 25, as noted above, Kelso et al. ‘891 in view of Ohashi and Mermod et al. renders claim 1 obvious from which claim 25 depends.
Claim 25 recites that the second chamber comprises compressed air wherein the compressed air is generated by filling of the first and third chambers with aqueous solution at atmospheric pressure.
Kelso et al. ‘891 teaches that the air gaps involve hydrostatic pressures. (page 10, lines 23-24)
Therefore, Kelso et al. ‘891 in view of Ohashi et al. and Mermod et al. renders claim 25 obvious.
XI.) Regarding applicant’s claim 26, as noted above, Kelso et al. ‘891 in view of Ohashi and Mermod et al. renders claim 5 obvious from which claim 26 depends.
Claim 26 recites that the aqueous phase in the third region comprises an elution .
Kelso et al. ‘891 teaches an elution buffer that would be in one of the regions. (page 8, lines 28-30)
Therefore, Kelso et al. ‘891 in view of Ohashi et al. and Mermod et al. renders claim 26 obvious.
XII.) Regarding applicant’s claim 28, as noted above, Kelso et al. ‘891 in view of Ohashi and Mermod et al. renders claim 26 obvious from which claim 28 depends.
Claim 28 recites the aqueous phase in the third region comprises a wash solution and the cartridge comprises a fourth region comprising air or an immiscible substance and a fifth region comprising an elution buffer, further comprising transporting the first and second populations of magnetic particles from the third region to the fifth region via the fourth region.
As noted above, Kelso et al. ‘891 teaches multiple regions.
In addition, Kelso et al. ‘891 teaches wash solutions and elution buffers. (page 8, lines 27-30)
Therefore, Kelso et al. ‘891 in view of Ohashi et al. and Mermod et al. renders claim 28 obvious.
XIII.) Regarding applicant’s claim 32, as noted above, Kelso et al. ‘891 in view of Ohashi and Mermod et al. renders claim 1 obvious from which claim 32 depends.
Claim 32 recites that the contacting comprises agitating a mixture comprising the sample and the first and second populations of magnetic particles.
Kelso et al. ‘891 teaches that the PMPs, sample, buffer, reagents, etc. of the first chamber are mixed (e.g., manually (e.g., shaking, inversion, etc.) or by mechanical means (e.g., sonication, magnetic streaming, etc.) to resuspend the PMPs and/or to allows binding of analyte to the capture reagent on the PMPs. (page 18, lines 4-7)
Therefore, Kelso et al. ‘891 in view of Ohashi et al. and Mermod et al. renders claim 32 obvious.
XIV.) Regarding claim 33, as noted above Kelso et al. ‘891 in view of Ohashi et al. and Mermod et al. renders claim 32 obvious from which claim 33 depends.
Claim 33 recites that agitating comprises shaking the cartridge.
As noted above, Kelso et al. ‘891 teaches that the PMPs, sample, buffer, reagents, etc. of the first chamber are mixed (e.g., manually (e.g., shaking, inversion, etc.) or by mechanical means (e.g., sonication, magnetic streaming, etc.) to resuspend the PMPs and/or to allows binding of analyte to the capture reagent on the PMPs. (page 18, lines 4-7)
Therefore, Kelso et al. ‘891 in view of Ohashi et al. and Mermod et al. renders claim 33 obvious.
XV.) Regarding applicant’s claim 34, as noted above, Kelso et al. ‘891 in view of Ohashi and Mermod et al. renders claim 13 obvious from which claim 34 depends.
Claim 34 recites applying the magnetic force forms an aggregate of the first and second populations of magnetic particles which aggregate is spatially aligned with an entrance to the first channel and wherein the entrance to the first channel comprises a tapered region that decreases in size from the first chamber to the first channel and facilitates transport of the aggregate from the first chamber to the second chamber via the first channel.
In Kelso et al. ‘891 in view of Ohashi et al. and Mermod et al. applying the magnetic force forms an aggregate of the first and second populations of magnetic particles which aggregate to pass through channels between adjacent regions.
Kelso et al. ‘891 in view of Ohashi et al. and Mermod et al. does not teach that the channels between adjacent regions comprises a tapered region that decreases in size.
It would have been obvious to one of ordinary skill in the art to configure the channels between adjacent regions in Kelso et al. ‘891 in view of Ohashi et al. and Mermod et al. to have any convenient shape including a tapered shape to reduce the amount of fluid being transferred with the aggregated magnetic particles.
Therefore, Kelso et al. ‘891 in view of Ohashi et al. and Mermod et al. renders claim 34 obvious.
XVI.) Regarding applicant’s claim 36, as noted above, Kelso et al. ‘891 in view of Ohashi and Mermod et al. renders claim 34 obvious from which claim 36 depends.
Claim 36 recites that the aggregate is spatially aligned with an entrance to the second channel, wherein the entrance to the second channel comprises a tapered region that decreases in size from the second chamber to the second channel and facilitates transport of the aggregate from the second chamber to the third chamber via the second channel.
Kelso et al. ‘891 in view of Ohashi et al. and Mermod et al. does not teach that the channels between adjacent regions comprises a tapered region that decreases in size.
It would have been obvious to one of ordinary skill in the art to configure the channels between any adjacent regions in Kelso et al. ‘891 in view of Ohashi et al. and Mermod et al. to have any convenient shape including a tapered shape to reduce the amount of fluid being transferred with the aggregated magnetic particles.
Therefore, Kelso et al. ‘891 in view of Ohashi et al. and Mermod et al. renders claim 36 obvious.
XVII.) Regarding applicant’s claim 38, as noted above, Kelso et al. ‘891 in view of Ohashi and Mermod et al. renders claim 13 obvious from which claim 38 depends.
Claim 38 recites that the transporting the first and second populations of magnetic particles from the first chamber to a second chamber of the cartridge by applying a magnetic force to the particles comprises placing a magnet adjacent the first chamber to cause formation of an aggregate comprising the magnetic particles, wherein the magnet is placed at a position such that the aggregate is spatially aligned with the entrance to the first and second channels.
In Kelso et al. in view of Ohashi et al. and Mermod et al. it would have been obvious to one of ordinary skill in the art to position the external magnetic force at a position such that the aggregate of the first and second magnetic particles is spatially aligned with the entrance to the first and second channels between the adjacent regions to effect transfer.
Therefore, Kelso et al. ‘891 in view of Ohashi et al. and Mermod et al. renders claim 38 obvious.
XVIII.) Regarding applicant’s claim 40, as noted above, Kelso et al. ‘891 in view of Ohashi and Mermod et al. renders claim 1 obvious from which claim 40 depends.
Claim 40 recites that the step of contacting a sample with a first population of magnetic particles and a second population of magnetic particles in a first region of a sample processing cartridge comprises loading of the sample into the first chamber of the sample processing cartridge by a user and wherein one or more of the remaining steps are carried out automatically by an instrument operably connected to the cartridge.
As noted above, Kelso et al. ‘891 teaches that a user places the sample and magnet particle into the cartridge.
Kelso et al. ‘891 in view of Ohashi et al. and Mermod et al. does not teach that one or more of the remaining steps are carried out automatically by an instrument operably connected to the cartridge; however, Kelso et al. teaches that magnetic is placed, the mixing is performed, and movement of the magnet are preformed automatically. (page 18, lines 4-7; page 28, lines 30-32)
It would have been obvious to one of ordinary skill in the art to modify Kelso et al. ‘891 in view of Ohashi et al. Mermod et al. to automate any of the steps of analyzing samples. Note, automating a manual process is obvious if the same result is accomplished. (MPEP 2144.04(III)
Therefore, Kelso et al. ‘891 in view of Ohashi et al. and Mermod et al. renders claim 40 obvious.
XIX.) Regarding applicant’s claim 63, as noted above, Kelso et al. ‘891 in view of Ohashi and Mermod et al. renders claim 1 obvious from which claim 63 depends.
Claim 63 recites that the ratio of the mass of the magnetic particles in the first population to the mass of the magnetic particles in the second population is from 3:1 to 1:100.
Kelso et al. ‘891 in view of Ohashi and Mermod et al. do not teach the ratio of the mass of the magnetic particles in the first population to the mass of the magnetic particles in the second population.
It would have been obvious to one of ordinary skill in the art to conduct routine engineering optimization experimentation and determine to provide a ratio of the mass of the magnetic particles in the first population to the mass of the magnetic particles in the second population of from 3:1 to 1:100 for a desired amount of target analytes, magnetic field strength and rate of processing.
Therefore, Kelso et al. ‘891 in view of Ohashi et al. and Mermod et al. renders claim 63 obvious.
XX.) Regarding applicant’s claim 64, as noted above, Kelso et al. ‘891 in view of Ohashi and Mermod et al. renders claim 63 obvious from which claim 64 depends.
Claim 64 recites that the ratio is 1:1, 2:1, 1:2, 3:1, 1:3, 1:10, 1:30, or 1:100.
Kelso et al. ‘891 in view of Ohashi and Mermod et al. do not teach the ratio of the mass of the magnetic particles in the first population to the mass of the magnetic particles in the second population.
It would have been obvious to one of ordinary skill in the art to conduct routine engineering optimization experimentation and determine to provide a ratio of the mass of the magnetic particles in the first population to the mass of the magnetic particles in the second population of 1:1, 2:1, 1:2, 3:1, 1:3, 1:10, 1:30, or 1:100 for a desired amount of target analytes, magnetic field strength and rate of processing.
Therefore, Kelso et al. ‘891 in view of Ohashi et al. and Mermod et al. renders claim 64 obvious.
2. Claim 9 is rejected under 35 USC 103 as being unpatentable over Kelso et al. ‘891 in view of Ohashi et al. and Mermod et al. as applied to claim 5 above and further in view of U.S. Patent No. 8,304,188 to Kelso et al. ‘891 (“Kelso et al. ‘188”) (cited by applicant)
I.) Regarding applicant’s claim 9, as noted above, Kelso et al. ‘891 in view of Ohashi and Mermod et al. renders claim 5 obvious from which claim 9 depends.
Claim 9 recites that that the cartridge is substantially planar and comprises a first plate placed in a spaced apart manner from a second plate, wherein the first and second plates are held in stationary position relative to each other.
Kelso et al. ‘891 in view of Ohashi et al, and Mermod et al. does not teach that the cartridge is substantially planar and comprises a first plate placed in a spaced apart manner from a second plate, wherein the first and second plates are held in stationary position relative to each other.
Kelso et al. ‘188 teaches a cartridge having a plurality of regions/chambers between which materials are transferred. The cartridge includes an upper and lower plates as shown in Fig. 2.
It would have been obvious to one of ordinary skill in the art to modify Kelso et al. ‘891 in view of Ohashi et al. and Mermod et al. to form the cartridge with upper and lower plates as taught by Kelso et al. ‘188 as a matter of design choice. Note, changes in shape as a matter of choice are obvious absent persuasive evidence that the particular configuration is significant. (MPEP 2144.04(IV)(B))
Therefore, Kelso et al. ‘891 in view of Ohashi et al., Mermod et al. and Kelso et al. ‘188 renders claim 9 obvious.
3. Claims 41, 50, 65 and 66 are rejected under 35 USC 103 as being unpatentable over Kelso et al. in view of Ohashi et al.
As noted above, Kelso et al. ‘891 teaches discloses devices that facilitate the magnetic separation of an analyte from a sample, and methods of use thereof. (page 1, lines 7-10)
The methods include contacting a sample with a population of paramagnetic particles (PMPs) in an aqueous phase in a first region of a sample processing cartridge (trans -interface magnetic separation (TIMS) cartridge) that comprises multiple (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, or more, or ranges therebetween (e.g., 2 or more)) discrete chambers (page 16, lines 33-34.
PMPs displaying capture reagents (e.g., nucleic acid hybridization probes, antibodies or antibody fragments, affinity agents (e.g., streptavidin, divalent nickel, etc.), etc.) for a desired analyte (e.g., DNA or RNA, agent displaying an epitope, affinity target (e.g., linked to biotin, displaying a His6 tag, etc.) etc.) are added by a user or pre-loaded into a chamber. (page 17, lines 6-10.
The PMPs are transported from the aqueous phase in the first region to an air phase in a second region of the cartridge by applying a magnetic force to the magnetic particles (see Fig. 2 for an air phase (air gap) in a second region of the cartridge; pg. 17, In 17-22)
Kelso et al. ‘891 does not teach a first population of magnetic particles and a second population of magnetic particles in an aqueous phase, wherein the magnetic particles in the second population are at least two-times larger in size than the magnetic particles in first population.
Ohashi et al. teaches a magnetic particle manipulation method and discloses a first population of magnetic particles (71) and a second population (60) of magnetic particles in an aqueous phase (32), wherein the magnetic particles and magnetic solid having a larger particle diameter than magnetic particles coexist in the liquid layer and the magnetic particles move along with the magnetic solid in the liquid layer by the magnetic field manipulation. (Fig. 1A-1D;[0018])
The magnet particles 71 and the magnet solid 60 passed through the gelled medium layer 21 move from the gelled medium layer 21 to the second liquid layer 32 by magnetic field manipulation. [0042]
The particle diameter of the magnetic particles (71) is preferable in the range of 0.1-20 µm and more preferably in the range of 0.5-10 µm. [0049] and the particle diameter of the magnetic solid (60) is preferably at least 50 µm, more preferably at least 100 µm and most preferably at least 150 µm (at least two times larger). [0055]
The magnetic particles (71) are moved along with the magnetic solid (60) by the magnet field. (Abstract)
Kelso et al. ‘891 teaches that a plurality of magnetic solids (60) can be used. [0064]
It would have been obvious to a person of ordinary skill in the art at the time of the invention to modify the processing cartridge of Kelso et al. ‘891 to have a first population of magnetic particles and a second population of magnetic particles in an aqueous phase and the magnetic particles in the second population are at least two-times larger in size than the magnetic particles in first population as taught by Ohashi et al. for purposes of eliminating a mal-effect relative to the background and the foreign materials as taught by Ohashi et al. [0006]
In response to claim 41 having been amended to recite that the second population of magnetic particles is incapable of associating with the target analyte (but not that the target analyte comprises nucleic acids as still recited in claim 24), Mermod et al. teaches the use of both functional magnetic particles (capture beads) and non-functional magnetic particles (carrier beads). [0110], [0167]
It would have been obvious to one of ordinary skill in the art before applicant’s effective filing date to modify Kelso et al. in view of Ohashi et al. to use functionalized magnetic particles to capture target analytes and non-functionalized magnetic particles for the magnetic solids of Kelso et al. to capture target analytes with the functionalized magnetic particles as taught by Mermod et al. and use the non-functionalized magnetic particles to collect, by aggregation, the functionalized magnetic particles with the target analytes trapped thereon.
I.) Regarding applicant’s claim 41, as noted above Kelso et al. ‘891 in view of Ohashi et al. and Mermod et al. teaches all the elements of claim 41.
Therefore, Kelso et al. ‘891 in view of Ohashi et al. renders claim 41 obvious.
II.) Regarding applicant’s claim 50, as noted above Kelso et al. ‘891 in view of Ohashi et al. and Mermod et al. renders claim 41 obvious from which claim 50 depends.
Claim 50 recites an air-gap positioned between the first chamber and the second chamber and the air chamber is an air-chamber positioned between the second chamber and the third chamber, wherein the first chamber is fluidically connected to the second chamber via a first channel, wherein the air-gap extends through the first channel, the second chamber is fluidically connected to the air-chamber via a second channel, and the air chamber is fluidically connected to the third chamber via a third channel.
Kelso et al. ‘891 teaches discloses devices that facilitate the magnetic separation of an analyte from a sample, and methods of use thereof. (page 1, lines 7-10)
The methods include contacting a sample with a population of paramagnetic particles (PMPs) in an aqueous phase in a first region of a sample processing cartridge (trans -interface magnetic separation (TIMS) cartridge) that comprises multiple (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, or more, or ranges therebetween (e.g., 2 or more)) discrete chambers (page 16, lines 33-34)
The PMPs are transported from the aqueous phase in the first region to an air phase in a second region of the cartridge by applying a magnetic force to the magnetic particles (see Fig. 2 for an air phase (air gap) in a second region of the cartridge; pg. 17, In 17-22)
Kelso et al. ‘891 teaches that some embodiments herein make use of an air gap (e.g., comprising one or more liquid/air interfaces) between two chambers to facilitate the transfer of PMPs/binding agents and analytes bound thereto from an initial chamber to a subsequent chamber while minimizing transfer of liquid (e.g., sample, reagents, contaminants, buffer, etc.). (page 17, lines 19-22)
Kelso et al. ‘891 teaches that in some embodiments a magnet is placed (e.g., manually by a user, by an automated device, etc.) on the distal side of the transfer surface to form a pellet of analyte-bound PMPs against the transfer surface. Movement of the magnetic field, laterally across the transfer surface, moves the collected PMPs through the pinned liquid of the first chamber, into the air gap between the first and second chambers). (page 18, lines 16-20)
It would have been obvious to provide the processing cartridge of Kelso et al. ‘891 in view of Ohashi et al. and Mermod et al. with three or more chambers as taught by Kelso et al. ‘891 separated by air gaps .
Kelso et al. ‘891 in view of Ohashi et al. and Mermod et al. does not teach an air chamber between second and third chambers.
It would have been obvious to one of ordinary skill in the art to provide an air phase chamber between any of the chambers in Kelso et al. ‘891 in view of Ohashi et al. and Mermod et al. for purposes of assuring collection of all the magnetic particles in such air phase chamber before transferring into the second chamber. Clearly passing the magnetic particles through an area/chamber that contains air does not adversely impact the teachings of Kelso et al. ‘891 inasmuch as Kelso et al. ‘891 passes the magnetic particles through the air gaps.
Note, mere duplication of parts (chambers) has no patentable significance unless a new and unexpected result is produced. (MPEP2144.04(VI)(B))
Therefore, Kelso et al. ‘891 in view of Ohashi et al. and Mermod et al. renders claim 51 obvious.
III.) Regarding applicant’s claim 65, as noted above, Kelso et al. ‘891 in view of Ohashi and Mermod et al. renders claim 41 obvious from which claim 65 depends.
Claim 65 recites that the ratio of the mass of the magnetic particles in the first population to the mass of the magnetic particles in the second population is from 3:1 to 1:100.
Kelso et al. ‘891 in view of Ohashi and Mermod et al. do not teach the ratio of the mass of the magnetic particles in the first population to the mass of the magnetic particles in the second population.
It would have been obvious to one of ordinary skill in the art to conduct routine engineering optimization experimentation and determine to provide a ratio of the mass of the magnetic particles in the first population to the mass of the magnetic particles in the second population of from 3:1 to 1:100 for a desired amount of target analytes, magnetic field strength and rate of processing.
Therefore, Kelso et al. ‘891 in view of Ohashi et al. and Mermod et al. renders claim 65 obvious.
IV.) Regarding applicant’s claim 66, as noted above, Kelso et al. ‘891 in view of Ohashi and Mermod et al. renders claim 65 obvious from which claim 66 depends.
Claim 66 recites that the ratio is 1:1, 2:1, 1:2, 3:1, 1:3, 1:10, 1:30, or 1:100.
Kelso et al. ‘891 in view of Ohashi and Mermod et al. do not teach the ratio of the mass of the magnetic particles in the first population to the mass of the magnetic particles in the second population.
It would have been obvious to one of ordinary skill in the art to conduct routine engineering optimization experimentation and determine to provide a ratio of the mass of the magnetic particles in the first population to the mass of the magnetic particles in the second population of 1:1, 2:1, 1:2, 3:1, 1:3, 1:10, 1:30, or 1:100 for a desired amount of target analytes, magnetic field strength and rate of processing.
Therefore, Kelso et al. ‘891 in view of Ohashi et al. and Mermod et al. renders claim 66 obvious.
Response to Arguments
Applicant’s arguments with respect to claims 1, 2, 5, 6, 9, 13, 16, 19, 21, 24-26, 28, 32-34, 36, 38, 40, 41, 50 and 63-66 have been considered but are moot because the new ground of rejection relies upon Mermod et al. as teaching the combined use of both functional magnetic particles (capture beads) and non-functional magnetic particles (carrier beads), rendering it obvious to one of ordinary skill in the art before applicant’s effective filing date to modify Kelso et al. ‘891 in view of Ohashi et al. to use functionalized magnetic particles to capture target analytes and non-functionalized magnetic particles for the magnetic solids of Kelso et al. ‘891 to capture target analytes with the functionalized magnetic particles as taught by Mermod et al. and use the non-functionalized magnetic particles to collect by aggregation the functionalized magnetic particles with the target analytes trapped thereon.
On page 15 of applicant’s response filed 04/16/2026 Applicant argues:
1. the combination of Kelso and Ohashi does not teach or suggest contacting a sample with a first population of magnetic particles and a second population of magnetic particles;
In response, it is noted that Ohashi et al. and Mermod et al. each teach contacting a sample with a first population of magnetic particles and a second population of magnetic particles
2. the combination of Kelso and Ohashi does not teach or suggest transferring both populations of the magnetic particles carrying a target analyte through air;
In response, it is noted that Kelso et al. ‘891 teaches transferring magnet particle carrying an analyte though and airlock.
3. the combination of Kelso and Ohashi does not teach or suggest the ratio of the mass of the magnetic particles in the first population to the mass of the magnetic particles in the second population of magnetic particles as claimed in new claims 63-66; and
In response, it is note that while Kelso et al. ‘891 and Ohashi et al. teach or suggest the ratio of the mass of the magnetic particles in the first population to the mass of the magnetic particles in the second population of magnetic particles as claimed in new claims 63-66, it would have been obvious to one of ordinary skill in the art to conduct routine engineering optimization experimentation and determine to provide a ratio of the mass of the magnetic particles in the first population to the mass of the magnetic particles in the second population of as recited in claims 63-66 for a desired amount of target analytes, magnetic field strength and rate of processing.
4. the use of the second population of magnetic particles as instantly claimed provides for superior transfer through air of magnetic particles carrying a target analyte.
In response, it is noted that the record does not establish that the use of non-functionalized magnetic solid particles in Kelso et al. ‘891 in view of Ohashi et al. and Mermod et al. would transfer magnetic particles carrying a target analyte through air any differently than applicant has argued.
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.
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/M.S.G./Examiner, Art Unit 1798
/CHARLES CAPOZZI/Supervisory Patent Examiner, Art Unit 1798
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