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 .
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.
Priority
Acknowledgment is made of the present application as a proper National Stage (371) entry of PCT Application No. PCT/US2018/062963, filed 11/29/2018, which claims benefit under 35 U.S.C. 119(e) to provisional application No. 62/632,219, filed 02/19/2018.
Status of the Claims
Claims 1-10, 12-17, 19 and 20 are pending; claims 1-6 are withdrawn; claims 11 and 18 are cancelled; claims 7, 14 and 17 are amended. Claims 7-10, 12-17, 19 and 20 are examined below.
Withdrawn Objections/Rejections
The previous rejection of claims 7 and 14 under 35 U.S.C. 112(a) are withdrawn in response to Applicant’s amendments to the claims.
The rejection of claim 17 under 35 U.S.C. 112(b) is withdrawn in response to Applicant’s amendment to the claims.
Claim Rejections - 35 USC § 103
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.
Claim(s) 7, 10, 13, 14, 17 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Siddiqi, US PG Pub No. 2003/0127396A1 in view of Yanagibayashi et al., WO 2016/079779A1 and Kreuwel et al., US Patent No. 6,764,859B1.
WO 2016/079779A1 is not in English. However, and English language translation is available by way of the US counterpart, US PG Pub No. 2017/0326509A1. The citations provided below correspond to the US PG Pub document.
Siddiqi teach a system comprising antibody bound paramagnetic microparticles (abstract, and particularly paras [0008], [0009], [0051], [0066]), a receptacle (abstract, para [0019], Figures 1, 2 and 3, and para [0050]) that is for holding test sample and the particles, and several electromagnets configured to generate an electromagnetic filed (for example, Figures 1, 2 and 3 and paragraphs [0022], [0023], [0072], more particularly Figure 7, para [0027] and claim 12, see also Figure 12). Regarding the receptacle, Siddiqi’s container is a container capable of holding sample and microparticle reagent, and as a result structurally addresses the claimed limitation “configured to hold a solution of the rare cells and the antibody-bound-paramagnetic microparticles”.
Siddiqi’s invention comprises, for example, arrangements (cited above) such that the magnets/electromagnets (plural, i.e. several, to generate an electromagnetic field, see also paras [0051], [0120]) are mobile, specifically throughout the disclosure regarding mobile magnetic sources, Siddiqi teach attachment to a drive mechanism and rotation mechanism (paras [0033], [0088]). The structure of Siddiqi reads on a movement mechanism comprising a first movement mechanism, see as it comprises a hub (see for example in embodiments comprising mobile magnets, magnet/magnets are attached to a support structure- for example, Figure 2, the support 22 addresses a hub, also para [0037], Figures 14, 15, embodiments describing movable support plate, see further para [0068] fixed to non-magnetic holding support to form an assembly), and a motor configured to rotate the hub (see para [0072], for moving the electromagnets and in turn an electric field about the receptacle). Siddiqi et al. teach the hub is configured to receive the receptable (a suitable container is removably mounted in the apparatus of the present invention (para [0019]), see also para [0074], container removably placed in holder).
Siddiqi’s electromagnetic field causes motion that allows the microparticles to be brought in contact with the targeted analytes for binding to generate bound particles. Siddiqi’s moves the magnets in a scanning motion, thereby sweeping the contents of the receptacle (i.e., mixing). See for example, abstract and paras [0018], [0049], [0053], [0054] the device of Siddiqi achieves magnetic mixing and separation.
Regarding the preamble of the claim, namely that the system is “for isolation of a rare cell population”, see further Siddiqi at paras [0061], [0063], Siddiqi teach their device can be used in methods for this same purpose as claimed (para [0061], useful for isolation of human rare cells required in various cell therapies).
Embodiments of Siddiqi differs from that which is claimed in that it is the magnets which the second mechanism translates (not the containers). See in addition to citations above, Siddiqi at for example Figure 12 and para [0091]-[0092], Siddiqi’s movement mechanism comprises a first mechanism that performs the function of generating a helical motion of the magnetic field, the first mechanism coupled to the electromagnetics, moving them and in turn the field around the receptacle (see motor 120 is a “mechanism” that rotates a screw 116, causing the assembly to move, i.e., is coupled to the motor 120 through the screw that causes the roll nuts to covert the rotary motion into linear motion moving assembly 125 vertically while the containers move, thereby causing the containers, and as such the electric field, to move around the receptacles). Siddiqi’s movement mechanism also comprises a second mechanism (motor 129 described at para [0095]), which causes movement (rotationally) of the receptacles (see Figure 1 showing modification for 1 container, Figure 12 shows multiple containers, for example the motor with a gear pulley and a timing belt).
Regarding linear motion see para [0069], see Siddiqi describes a simple linear motion mechanism comprising a slider with a rectangular notch or groove, riding on rail with a corresponding rectangular shape, further a gear rack and pinion mechanism comprising a rectangular gear teeth bar (rack) and a mating gear teeth pulley taught as advantageous when accuracy in the distance between magnet and container is desired (a linear rail riding on linear guides, the movable structure (container or magnet) coupled to the rail and moved by a motor to achieve translation).
Nonetheless, see also para [0120] of Siddiqi, teaching those of ordinary skill in the art will appreciate that various adaptations and modifications of the described preferred embodiments can be configured without departing form the scope and spirit of the invention of Siddiqi. See at para [0120], Siddiqi teach that although relative angular motion is achieved by rotating the container or orbiting the magnet, alternative mechanism will be obvious to a skilled artisan, Siddiqi teaching movement between the magnetic source and the particles may be affected by moving the magnet or the container by linear motion mechanism using appropriate linear acceleration.
While the embodiment of Siddiqi described above (shown at Figure 12) is extremely similar to the system as claimed in that the movement mechanism comprises a first and second movement mechanisms, one for rotational motion and one for translational motion, it differs in that the rotational and translational motions are applied to the containers and the magnets respectively, rather than the opposite as is claimed (as claimed it is the position of the container that is translated by the second mechanism, and it is the magnet that is rotated by the first mechanism).
Yanagibayashi et al., is similar to Siddiqi, see Yanagibayashi Figure 5, in that the structure shown is demonstrating a system that manipulates particles, see the system comprising a vial/container with magnetic particles, and a magnet (191) that is on a stationary axis capable of being moved along the length of the vial/container (see Figure 5 the arrow showing the motion), and a mechanism capable of rotating the container (see para [0092] describes rotation of the container holding element to rotate the vial/container while the magnet moves up and down, interpreted as describing motion that would be considered a helical motion magnetic field). See at para [0092] Yanagibayashi teach, the system can be designed so that the magnet does the rotating by way of revolving guide bar around the container. See para [0092] Yanagibayashi teach an apparatus may further implement both (rotation and revolving container motion).
Both the different embodiments of Siddiqi, as well as this disclosure of Yanagibayashi et al., support that the configuration of the structural components to achieve motion of a magnet are subjective. What appears consistently required (throughout these prior art references) is the motion of the magnetic field (for example, while the configuration of movement is recited as subjective (relative to the parts that move), both describe motion that is interpreted as helical motion, i.e., motion that goes around up the length of a container containing the particles).
See further Kreuwel et al. teaching a methods comprising magnetic particle mixing with fluids (abstract), Kreuwel et al. also teach movement of magnetics with respect to positions of containers and/or by moving the containers with respect to the positions of the magnets (also at the abstract, col. 4, lines 6-11, lines 20-26 and 35-41, col. 6, lines 3-5, see Kreuwel at the claims (claims 1, 9 and 12, describing moving the magnets and also oscillating the containers with respect to the positions of the magnets). Kreuwel et al. teach the slightest movement of either one of the magnets or the containers with respect to each other will result in sudden strong changes of the magnetic field to which the particles in the container are subjected to (col. 4, lines 49-53).
As such, it would have been prima facie obvious to one having ordinary skill in the art to have modified the design of Siddiqi such to allow rotation of the magnet (by a first mechanism as part of the movement mechanism) and translation of the container (by a second mechanism of the movement mechanism, translating the component up and down while the magnet rotates around via the hub) as an obvious matter of design choice. In particular, Siddiqi’s system reads on the claimed system except for in Siddiqi, it is the magnet that experiences translational motion, and the container which rotates (or in other embodiments, the alternative, however, not both). The modification, namely shifting these mechanisms such that it is the magnet that rotates and the container that translates position would not have modified the magnetic field impact in way to render it inoperable (the magnetic field would still exhibit helical motion), rather Kreuwel et al. supports motion of either would result in strong changes of the magnetic field. As a result, interchanging these parts/motions would be an obvious matter of design choice (combining the helical motion of the magnet with the translation motion of the container). The rationale that the modification would be an obvious matter of design choice is further supported by Yanagibayashi and Kreuwel, Yanagibayashi suggests the interchangeability of these motion actuations (regarding how the magnet is moved about a container and a container is moved above a magnet) and Kreuwel who suggest the combination of rotation of magnet and oscillation (translation) of the container to influence magnetic field; this is similarly supported by Siddiqi’s different embodiments, exhibiting different configurations to move the magnetic field and Siddiqi’s teaching at para [0120] supporting the invention of Siddiqi accommodates adaptations within the spirit of their invention.
One having ordinary skill would have a reasonable expectation of success because both Siddiqi, Yanagibayashi and Kreuwel et al. supports the feasibility/ease of changing up the configuration for achieving magnetic field (by way of their different embodiments) through the combination of motion of magnet/electromagnets and motion of the container. One having ordinary skill in the art would have a reasonable expectation of success modifying Siddiqi as set forth in detail above because based on Siddiqi, Yanagibayashi and Kreuwel, the combination of magnet motion and container motion is known and implemented by those having ordinary skill in the art (the combination of motions is a technique already realized by those of ordinary skill in the art, and as such one would have a reasonable expectation of success modifying Siddiqi to achieve both at once).
Regarding claim 10, Siddiqi and the combination of the cited art describes the mobile components as being capable of moving up and down and around the receptacle, and as such Siddiqi is considered to address a motion that is “helical” around the receptacle (see for example, Siddiqi paras [0023], [0047], [0053] and claims 20, 29, 32, 36).
Regarding claim 13, see Siddiqi teach a computing device with non-transitory computer readable medium programmed for control (e.g., see para [0155] teaching motor driven by computer programmable controller driver, thereby indicating a computing device consistent with that claimed).
Regarding claim 14, see as cited above, Siddiqi is teaching a device as claimed (capable for isolation, specifically isolation of analyte such as a rare cell population, see as cited above). Siddiqi teaching the structures of a receptacle configured to hold a solution of the rare cells and rare cell binding paramagnetic particles, an electromagnet to generate an electric field, and a movement mechanism as claimed (see as cited in detail above).
Regarding claim 17, see Siddiqi as cite in detail above addresses the movement mechanism having a helical motion of the electromagnetic field relative to the receptacle.
Regarding claim 20, see Siddiqi teach a computing device with non-transitory computer readable medium programmed for control (e.g., see para [0155] teaching motor driven by computer programmable controller driver, thereby indicating a computing device consistent with that claimed).
Claim(s) 8, 9, 15 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Siddiqi, Yanagibayashi, and Kreuwel as applied to claims 7 and 14 above, in view of Stoianovici et al., WO2017/184928A1.
Siddiqi, Yanagibayashi and Kreuwel et al. teach an isolation system/device substantially as claimed, however, Siddiqi fails to teach the system/device further comprising a microscope slide for receiving the isolated rare cells (claims 8 and 15); Siddiqi also fails to teach the system/device further comprising a magnet for facilitating transfer of the rare cells bound to the particles (claims 9 and 16).
Stoianovici et al. also teach a system/device for rare cell isolation, Stoianovici teaching isolation of cells and then transferring cells to a microscope slide for the purposes of microscopic imaging (downstream analysis, paras [0008], [0023], [0024] providing device, a slide included therewith, [0028], claim 1).
It would have been prima facie obvious, to one having ordinary skill in the art at the time the claimed invention was effectively filed, to have modified the system/device of Siddiqi, Yanagibayashi and Kreuwel, to further include therewith, a microscopic slide, one motivated to provide a slide for the purpose of making the system amenable to further downstream application. Specifically, by providing a microscope slide, the system is further capable of receiving/transferring the rare cells that have been isolated, to the slide for further downstream application, such as microscopic imaging/analysis (as in Stoianovici, se Stoianovici demonstrate it is desirable to further collect rare cells for such downstream analysis). One having ordinary skill in the art would have a reasonable expectation of success, because Stoianovici already demonstrate providing a microscope slide with a rare cell isolations system/device.
Regarding claims 9 and 16, As discussed, Siddiqi teach a system/device substantially as claimed (see as cited in detail previously above), specifically isolating rare cells from a sample. However, as indicated above fails to teach the system/device further comprising a magnet for facilitating transfer of the rare cells bound to the particles.
Stoianovici further teaches (for example at claim 9), including an additional magnetic source of their device for cell isolation, the additional magnetic source for applying a magnetic force to collect the particle bound isolated cells for transfer to another surface (see also page 3, lines 8-9.
It would have been further obvious to have modified the isolation system/device of Siddiqi and the cited prior art in order to add a further magnet (magnetic source) for allowing the device to be used for the purpose of transferring isolated cells (for example for the purpose of collecting the cells for further downstream applications, as taught by Stoianovici). One having ordinary skill in the art would have a reasonable expectation of success, modifying the system of Siddiqi to further including a magnet for transfer as in Stoianovici because the rare cells of Siddiqi are bound to magnetic particles. As such, modifying to include a further magnet for transfer would be expected successful, since the cells would be amenable to magnetic manipulation (as a result of being bound to the particles).
Claim(s) 12 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Siddiqi in view of Yanagibayashi and Kreuwel et al., as applied to claims 7 and 14, and further in view of Sajja et al., Application of Magnetic Particle Tracking Velocimetry to Quadrupole Magnetic Sorting of Porcine Pancreatic Islets, Biotechnol. Bioeng., 108(9), (2011), p. 2107-2117.
Siddiqi and Yanagibayashi teach an isolation system/device substantially as claimed (see as cited above).
However, Siddiqi fails to teach the system comprising a video camera fixed in a location relative the magnetic field, to provide visualization during motion (claims 12 and 19).
However, see Sajja et al. teach using a video camera to measure magnetophoretic mobility of particles in a solution of known viscosity subject to a magnetic field (e.g., abstract), specifically, Sajja teach that by videotaping the movement of immunomagnetically labeled particles through known viscosity medium and magnetic susceptibility, information can be obtained to calculate a particle’s magnetophoretic mobility (see page 2, paras 2 and 4); that this information, for example, allows one to predict optimized flow parameters to isolate magnetic particles from nonmagnetic particles (page 8, para 5).
It would have been further prima facie obvious to one having ordinary skill before the effective filing date to have modified the system/device such to add a video camera at a fixed location relative to the magnetic field (as in Sajja), in a way that allows the device to accommodate visualization of the particles in motion when magnetic field is applied during its use, for example, to accommodate the system for the purpose of mobility studies, for example as in Sajja, to determine parameters like magnetophoretic mobility, which for example could be used for optimization of isolation. One having ordinary skill would have a reasonable expectation of success because Sajja demonstrates those of ordinary skill at the time of effective filing were using (knew how to use) video camera recording to observe particle motion (was already demonstrated, as such one would expect success making the modification).
Response to Arguments
Applicant's arguments filed 02/02/2026 have been fully considered but they are not persuasive for the following reasons.
Regarding remarks at page 7, see as indicated above, the previous rejections of claims under 35 U.S.C. 112(a) and 35 U.S.C. 112(b) are withdrawn in response to Applicant’s amendments to the claims.
Regarding the rejection of claims under 35 U.S.C. 103 (remarks pages 7-10), Applicant argues that Siddiqi does not disclose movement mechanisms for movement of the electromagnets and the receptacle as recited at claims 7 and 14. Specifically, arguments assert that Siddiqi does not disclose a second movement mechanism that translates the receptacle up and down while the hub rotates about the receptacle, nor that a linear rail is disposed along a central, vertical axis of the hub, further that the additionally cited art does not address this asserted deficiency (see remarks page 8).
However, this argument is not persuasive in light of the rejection detail above. It is maintained that it is the combination of the cited prior art which establishes that he claimed invention is prima facie obvious. As detailed in the rejection, embodiments of Siddiqi differs from that which is claimed in that it is the magnets which the second mechanism translates (not the containers), that in addition to the initial citations of the reference, Siddiqi at for example Figure 12 and para [0091]-[0092], Siddiqi’s movement mechanism comprises a first mechanism that performs the function of generating a helical motion of the magnetic field, the first mechanism coupled to the electromagnetics, moving them and in turn the field around the receptacle (see motor 120 is a “mechanism” that rotates a screw 116, causing the assembly to move, i.e., is coupled to the motor 120 through the screw that causes the roll nuts to covert the rotary motion into linear motion moving assembly 125 vertically while the containers move, thereby causing the containers, and as such the electric field, to move around the receptacles).
Siddiqi’s movement mechanism also comprises a second mechanism (motor 129 described at para [0095]), which causes movement (rotationally) of the receptacles (see Figure 1 showing modification for 1 container, Figure 12 shows multiple containers, for example the motor with a gear pulley and a timing belt).
The primary reference, as a result, does encompass this concept of dual motion.
Also as cited above, at para [0120] of Siddiqi, the reference is teaching those of ordinary skill in the art will appreciate that various adaptations and modifications of the described preferred embodiments can be configured without departing form the scope and spirit of the invention of Siddiqi. See at para [0120], Siddiqi teach that although relative angular motion is achieved by rotating the container or orbiting the magnet, alternative mechanism will be obvious to a skilled artisan, Siddiqi teaching movement between the magnetic source and the particles may be affected by moving the magnet or the container by linear motion mechanism using appropriate linear acceleration.
While the embodiment of Siddiqi described above (shown at Figure 12) is extremely similar to the system as claimed in that the movement mechanism comprises a first and second movement mechanisms, one for rotational motion and one for translational motion, the Office acknowledges that it differs in that the rotational and translational motions are applied to the containers and the magnets respectively, rather than the opposite as is claimed (as claimed it is the position of the container that is translated by the second mechanism, and it is the magnet that is rotated by the first mechanism).
However, based on the additionally cited prior art, it is maintained that it would have been prima facie obvious to one having ordinary skill in the art to have modified the design of Siddiqi such to allow rotation of the magnet (by a first mechanism as part of the movement mechanism) and translation of the container (by a second mechanism of the movement mechanism, translating the component up and down while the magnet rotates around via the hub) as an obvious matter of design choice.
As noted in the rejection, Siddiqi’s system reads on the claimed system except for in Siddiqi, it is the magnet that experiences translational motion, and the container which rotates (or in other embodiments, the alternative, however, not both). The modification, namely shifting these mechanisms such that it is the magnet that rotates and the container that translates position would not have modified the magnetic field impact in way to render it inoperable (the magnetic field would still exhibit helical motion, this feature of Siddiqi would be retained, even as modified), rather Kreuwel et al. supports motion of either would result in strong changes of the magnetic field. As a result, interchanging these parts/motions would be an obvious matter of design choice (combining the helical motion of the magnet with the translation motion of the container).
The rationale that the modification would be an obvious matter of design choice is further supported by the additionally cited prior art, Yanagibayashi and Kreuwel, Yanagibayashi suggests the interchangeability of these motion actuations (regarding how the magnet is moved about a container and a container is moved above a magnet) and Kreuwel who suggest the combination of rotation of magnet and oscillation (translation) of the container to influence magnetic field; this is similarly supported by Siddiqi’s different embodiments, exhibiting different configurations to move the magnetic field and Siddiqi’s teaching at para [0120] supporting the invention of Siddiqi accommodates adaptations within the spirit of their invention.
It is maintained that one having ordinary skill would have a reasonable expectation of success because both Siddiqi, Yanagibayashi and Kreuwel et al. supports the feasibility/ease of changing up the configuration for achieving magnetic field (by way of their different embodiments) through the combination of motion of magnet/electromagnets and motion of the container. See for example, referring to Siddiqi, para [0120] of Siddiqi, teaching those of ordinary skill in the art will appreciate that various adaptations and modifications of the described preferred embodiments can be configured without departing form the scope and spirit of the invention of Siddiqi. See at para [0120], Siddiqi teach that although relative angular motion is achieved by rotating the container or orbiting the magnet, alternative mechanism will be obvious to a skilled artisan, Siddiqi teaching movement between the magnetic source and the particles may be affected by moving the magnet or the container by linear motion mechanism using appropriate linear acceleration.
Also, see for example, at para [0092] Yanagibayashi teach, the system can be designed so that the magnet does the rotating by way of revolving guide bar around the container. See para [0092] Yanagibayashi teach an apparatus may further implement both (rotation and revolving container motion).
As noted in the rejection above, further, one having ordinary skill in the art would have a reasonable expectation of success modifying Siddiqi as set forth in detail above because based on Siddiqi, Yanagibayashi and Kreuwel, the combination of magnet motion and container motion is known and implemented by those having ordinary skill in the art (the combination of motions is a technique already realized by those of ordinary skill in the art, and as such one would have a reasonable expectation of success modifying Siddiqi to achieve both at once).
Regarding remarks pages 8-10, Applicant refers to remarks discussed above (specific to the independent claims). For the reasons discussed above, the arguments are not persuasive.
For these reasons, the rejection is maintained.
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.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ELLEN J MARCSISIN whose telephone number is (571)272-6001. The examiner can normally be reached M-F 8:00am-4:30pm.
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/ELLEN J MARCSISIN/Primary Examiner, Art Unit 1677