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 .
Response to Amendment
The Amendment filed 07/02/2025 has been entered. Claims 1-8 and 10-15 remain pending in the application. Claim 9 is canceled. Claims 10-15 are withdrawn. Claims 1-8 are being examined herein.
Status of Objections and Rejections
All rejections of claim 9 are obviated by Applicant’s cancellation.
The rejections of claims 1-8 under 35 U.S.C. 102 and 35 U.S.C. 103 are being withdrawn in view of Applicant’s amendment.
New grounds for rejection under 35 U.S.C. 103 are necessitated by Applicant’s amendments.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 06/06/2025 is being considered by the examiner.
Claim Objections
Claim 1 is objected to because of the following informalities:
Lines 18-19, “the magnet a ring magnet surrounding ...” should read “the magnet is a ring magnet surrounding …”
Appropriate correction is required.
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.
Claims 1-8 are rejected under 35 U.S.C. 103 as being unpatentable over Graham et al. (US 20170016922 A1)(Provided in Applicant’s IDS of 01/27/2022) in view of Haselton et al. (US 20140272937 A1)(Provided in Applicant’s IDS of 01/27/2022).
Regarding claim 1, Graham teaches a biological component concentration fluid assembly (para. 0133), comprising magnetizing microparticles that are surface-activated to bind with a biological component or which are bound to the biological component (abstract, paras. 0134 and 0136-037);
a multi-fluid density gradient column (liquid layers of different densities in a liquid column contained in a vessel)(para. 0133), including:
a first fluid layer (zone 1) having a first fluid density (para. 0134), and
a second fluid layer (zone 2) having a second fluid density that is greater than the first fluid density and positioned along the multi-fluid density gradient column beneath the first fluid layer (para. 0134), wherein the second fluid layer is formulated to interact with a surface of the magnetizing microparticles when received from the first fluid layer of the multi-fluid density gradient column that is positioned thereabove (para. 0134);
a third fluid layer (zone 3) having a third fluid density that is greater than the second fluid density and positioned along the multi-fluid density gradient column beneath the second fluid layer, wherein the third fluid layer is formulated to further interact with the surface of the magnetizing microparticles when received from the second fluid layer of the multi-fluid density gradient column that is positioned thereabove (para. 0134); and
a magnet (para. 0133) to attract and draw the magnetizing microparticles from the first fluid layer, through the second fluid layer, and into the third fluid layer (para. 0133-0134).
Graham further teaches the magnet is at the bottom of the fluid layers to selectively move and separate cells that are tagged with magnetic particles (para. 0179) by pulling the magnetic particle-tagged cells through a fluid layers with a specific gravity that exceeds that of the cells and debris alone (paras. 0133, 0174 and 0179). Graham further teaches the magnet can be moved to various areas of the column (para. 0133).
Graham does not explicitly teach the magnet is a ring magnet surrounding an exterior circumference of the multi-fluid density gradient column and vertically movable along the multi-fluid density gradient column.
However, Haselton teach a device for separating and concentrating whole cells utilizing magnetic particles. Haselton teaches the use of a ring magnet surrounding an exterior circumference of a vessel (Fig. 2) to pull whole cells adsorbed to reactant-coated magnetic particles through processing solution (Fig. 2 and paras. 0033 and 0069) along the vessel in the vessel’s longitudinal direction (Fig. 2).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have substituted the magnet taught by Graham with the external ring magnet taught by Haselton because one of ordinary skill in the art would accordingly have recognized the magnetic ring would result in the predictable result of providing a magnetic that is movable along a vessel (column) in the vessel’s longitudinal direction for separating magnetic particle-tagged cells by pulling the magnetic particle-tagged cells through the fluid layers (Haselton, Fig. 2 and paras. 0033 and 0069).
The teachings of Graham as modified by Haselton yield a ring magnet surrounding an exterior circumference of the multi-fluid density gradient column and vertically (the longitudinal direction of Graham’s column) movable along the multi-fluid density gradient column to direct the magnetizing microparticles from the first fluid layer through the second fluid layer and into the third fluid layer.
Regarding claim 2, modified Graham teaches all of the elements of the current invention as stated above with respect to claim 1. Graham further teaches wherein the first fluid layer and the second fluid layer are in direct fluid communication with one another and are phase separated from one another at a first fluid interface, and wherein the second fluid layer and the third fluid layer are in direct fluid communication with one another and are phase separated from one another at a second fluid interface (paras. 0133 - 0134, each zone is contiguous with the adjacent zone, and materials selected for the zones are poorly miscible with each other).
Regarding claim 3, modified Graham teaches all of the elements of the current invention as stated above with respect to claim 1. Graham further teaches wherein the magnetizing microparticles are loaded in the first fluid layer (para. 91; para. 0134, magnetic complex of molecule of interested MOI proceeds from the uppermost layer with the lowest density to the lowermost layer with the highest density, leaving behind unbound reactant in the lower-density layers, evidencing the magnetic complex is loaded in the uppermost layer).
Regarding claim 4, modified Graham teaches all of the elements of the current invention as stated above with respect to claim 1. Graham further teaches wherein the magnetizing microparticles are separate from the multi-fluid density gradient column (para. 0154, magnetic particle tagged red blood cells are pre-prepared. Paras, 0154, 0157 and 0159, pre-prepared magnetic particle tagged red blood cells in a 3-fluid zone set-up) and are formulated to be introduced to the first fluid layer (interpreted as an intended use. Paras. 0154, 0157 and 0159, the pre-prepared magnetic are introduced to zone 1).
Regarding claim 5, modified Graham teaches all of the elements of the current invention as stated above with respect to claim 1. Graham further teaches wherein the magnetizing microparticles are dispersed in a loading fluid (para. 0154, magnetic-particle-tagged red blood cells are in a pre-prepared fluid ready to be dispensed by a pipette. Paras, 0154, 0157 and 0159, pre-prepared magnetic particle tagged red blood cells in a 3-fluid zone set-up) to be introduced to the first fluid layer to mix with the first fluid layer, or the loading fluid becomes the first fluid layer with the pre- dispersed magnetizing microparticles (interpreted as an intended use. Para. 0159, the pre-prepared magnetic particles tagged red blood cells are in Zone 1).
Regarding claim 6, modified Graham teaches all of the elements of the current invention as stated above with respect to claim 1. Graham teaches an apparatus comprises a column of liquid zones of different densities and a magnet for separation of biomolecules (para. 0133). Graham discloses in the third method (paras. 0157- 0159) that utilizes specific antibody-antigen binding to separate and subsequently detect the presence of red blood cells RBCs with a certain type of surface antigen. Graham discloses zone 1 includes magnetic particles that are tagged with the antibody for the surface antigen (surface binding fluid), where the RBCs with the antigen (biological component) binds with a surface of the magnetic particles through to the antibody (para. 0159), and then zone 2 (the second fluid layer) is a wash fluid (para. 0159), that separate the RBCs that are bound the magnetic particles from the unbound RBCs (para. 0159). Graham further discloses in the subsequent zones, anti-human globulin-tagged enzyme is used to further binds the RBCs-magnetic particles to generate signals for qualitative detection.
Graham fails to teach the third fluid (zone 3) is an elution fluid where the biological component is released from the surface of magnetizing microparticles.
However, Graham teaches the apparatus can also be used for purification processes, which require release of magnetic particles before more processing is performed (para. 0132) on the material of interest. Graham teaches the dissociation of material of interest from the magnetic particles is particularly valuable as a step in the purification of cells or molecules and can involve urea or guanidine solutions, pH changes, enzymatic cleavage and other means.
Therefore, It would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the apparatus of the third method to have zone 3 (the third fluid) to be a fluid that involves urea or guanidine solution or a fluid that causes pH changes, enzymatic cleavage and other means to promote dissociation of the RBCs from the magnetic particles (an elution fluid) where the RBCs are released from the surface of magnetizing microparticles in order for obtain purified RBCs for additional processing with a reasonable expectation of success (para. 0132) (MPEP 2143)(I)(G).
Regarding claims 7, modified Graham teaches all of the elements of the current invention as stated above with respect to claim 1. Graham teaches an apparatus comprises a column of liquid zones of different densities and a magnet for separation of biomolecules (para. 0133). Graham discloses in the third method (paras. 0157- 0159) that zone 1 includes antibody-tagged magnetic particles and sample, and then zone 2 (the second fluid layer) is a wash fluid with a higher density than zone 1(para. 0159).
Graham fails to explicitly teach wherein a density difference of zone 1 (the first fluid layer) relative to zone 2 (the second fluid layer) is from about 50 mg/ml to about 3 g/ml.
However, Graham teaches specific gravity is a zone design consideration (0094). Graham further teaches another sample use of the apparatus that involved antibody-tagged magnetic particles in para. 0083. Graham discloses zone 1 comprises magnetic particles with specific gravity of 1.1 to 1.3, the suspending liquid of specific gravity of 1.0 to 1.15 and the sample of specific gravity of 1.0 to 1.15, and zone 2 has a denser separating liquid of specific gravity of 1.3 to 2.0 (para. 0083). Based on Graham’s disclosure above, one of ordinary skill in the art can determine that the specific gravity of zone 1 based on the weighted average of the magnetic particles, the suspending liquid and the sample, which is between >1.0 to <1.3, and thus the specific gravity difference of zone 1 relative to zone 2 is greater than 0.0 and less than 1.0, which means the density difference of zone 1 relative to zone 2 is between 0 g/mL to 1.0 g/mL, exclusive.
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have substituted the density difference of zone 1 relative to zone 1 taught by the third method to be between 0 g/ mL to 1.0 g/mL, exclusive as taught by the example in para. 0083, with a reasonable expectation of success (para. 0083) (MPEP 2143)(I)(G).
In addition, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have selected the density difference of zone 1 relative to zone 2 in the range of 50 mg/mL to 1 g/mL the portion of Graham’s teaching that corresponds to the claimed range (MPEP244.05(I)).
Regarding claim 8, modified Graham teaches all of the elements of the current invention as stated above with respect to claim 1. Graham further teaches wherein the magnetizing microparticles include paramagnetic microparticles (para. 0055).
Response to Arguments
Applicant’s arguments, see pages 6-7, filed 07/02/2025, with respect to the rejections under 35 U.S.C. 102 and 103 have been fully considered and are persuasive. The rejection of claims 1-8 have been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Haselton et al. (US 20140272937 A1), provided in the Applicant’s IDS of 01/27/2022. Please see “Claim Rejections - 35 USC § 103” above for details of the rejection.
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.L.C./Examiner, Art Unit 1758
/MARIS R KESSEL/Supervisory Patent Examiner, Art Unit 1758