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.
Status of the Claims
Claims 2-7 have been canceled by Applicant’s amendment filed 05/22/2026. Claim 1 has been amended. New claims 8-11 have been added. Claims 1 and 8-11 are pending and examined herein.
Priority
This application, filed 10/05/2023, is a 371 of PCT/KR2021/016852, filed 11/17/2021, and claims benefit of REPUBLIC OF KOREA KR10-2021-0144086 filed on 10/26/2021. This priority is acknowledged and the claims examined herein are treated as having an effective filing date of 10/26/2021.
Information Disclosure Statement
The Information Disclosure Statements filed on 10/05/2023 are acknowledged and have been considered.
Claim Objections
Claim 9 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Amended Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1 and 9-11 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites “…(c) introducing a washing tip having a hollow portion, to an outer surface of which the magnetic bead immune complexes are attached, into a detection chamber…”. The claim is indefinite because there are multiple possible conflicting interpretations based on the claim language “to an outer surface”. For example, it is unclear if the claim language is to be interpreted as the outer surface refers to the outer surface of the washing tip specifically, or to another outer surface not on the washing tip. As there are multiple potential conflicting interpretations of the claim language, these claims are indefinite.
Claim 8 recites “…wherein prior to the step (c), the method further comprises…”. The claim is indefinite because, under the broadest reasonable interpretation, this means that the method steps recited after this claim language could occur even before step (a) or (b). This creates antecedent basis issues because, for example, claim 8 recites “…capturing the magnetic bead immune complexes…” which have not been generated prior to step (a).
Appropriate correction is required.
Amended 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.
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, 10, and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Fritchie et al. (U.S. Patent No. 8,222,048), (referred to herein as Fritchie), in view of Kim et al. (2017). “Integrated magnetic bead–quantum dot immunoassay for malaria detection”. ACS sensors, 2(6), 766-772. (referred to herein as Kim).
Regarding claims 1 and 11, Fritchie teaches a plate-based laboratory automation system and method used for performing immunoassays (abstract). Fritchie teaches that this system uses “inverse magnetic particle processing” to transfer magnetic particles and immunoassay products between the wells of the plates (abstract). Fritchie teaches that in the assay, a magnetic microparticle is coated with antibodies, and the assay is intended to look for antigens in the sample (column 8, lines 3-5). Fritchie teaches that a second antibody is labeled with a chemiluminescent label, and this second antibody is not attached to a magnetic microparticle (column 8, lines 5-7). Fritchie teaches that the antibody and antigen with attach in the following order: antibody on magnetic microparticle-antigen-antibody-chemiluminescent label, and then the magnetic microparticle is washed off (column 8, lines 7-11). Fritchie teaches that the amount of antibody-antigen-enzyme is measured by adding pre-trigger solution and trigger solution and measuring the light produced, and this type of immunoassay produces light when combined with its substrate, i.e., a specific binding member (column 8, lines 11-15). Fritchie teaches that the chemiluminescent reaction offers high sensitivity and ease of measurement (column 8, lines 15-16). Fritchie teaches that the magnetic particles are transferred using hollow plastic tips with magnetic rods located in the hollow tip, which adhere the magnetic particle complexes onto the outer surface of the tip (column 28, lines 34-36; Fig. 15). Fritchie teaches that in the capture, release, and wash steps, the magnetic rod and tip comb is moved up and down several times in the micro-wells which contain reagents such as washing solution (column 28, lines 60-61; column 29, lines 4-8; column 29, lines 11-20). Fritchie also teaches that the magnetic bead complexes can be dispersed into the chambers/wells in the detection by moving the magnetic beam up within the hollow portion of the washing tip (Fig. 15E and 15F).
Fritchie teaches that the required incubation steps are performed on the entire micro-well plate, and the amount of time that magnetic microparticles remain in a micro-well is deemed the incubation time or a portion thereof (column 35, lines 14-17). Fritchie also teaches that the moving and incubating of the magnetic microparticles through the various micro wells containing the sample, the wash buffer, the conjugate, and the pre-trigger solution (column 35, lines 17-20). Fritchie teaches that after the magnetic microparticles are incubated in the micro-wells containing the pre-trigger solution, the luminescent material, is released and the quantity of photons emitted is determined by a luminescence reader (column 35, lines 24-28).
However, Fritchie does not teach removing the magnetic bead immune complexes from the detection chamber prior to the optical inspection, or that the removal of the magnetic bead immune complexes from the detection chamber in the step (f) prevents the magnetic beads from absorbing and scattering an optical signal during the optical inspection, thereby reducing a bias signal.
Kim teaches an immunoassay method using magnetic beads for capture of an analyte for disease detection for point-of-care tests (abstract). Kim teaches that the method uses magnetic beads conjugated to antibodies, and a secondary anti-mouse HRP conjugate (page 767, 3rd full paragraph). Kim also teaches the removal of magnetic beads from the detection chamber (plate well) prior to analyte measurement via fluorescence (Fig. 1). Kim teaches that since scattering from the magnetic beads increases the background signal at shorter wavelengths and autofluorescence of the beads increases the background signal, elution of the particles from the complex significantly improves the sensitivity of the assay, and that based on their previous work, elution improves the signal-to-noise ratio of the assay by 6.7-fold (page 769, column 1, 1st paragraph).
It would have been obvious to person of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method taught by Fritchie to remove the magnetic beads from the detection well to reduce signal bias, as disclosed in Kim, in order to increase signal detection/sensitivity of the analyte measurement assay by reducing the background noise caused by the scattering as taught by Kim. A person of ordinary skill would have had a reasonable expectation of success in removing the magnetic beads from the detection chamber, the removal of the beads from a well/chamber is already taught in the bead transfer steps of Fritchie, and it is merely applying the same technique to the detection chamber in for improvement to the base method.
Regarding claim 8, Fritchie teaches that during the collection of the magnetic particles from the micro-wells of a micro-well plate, the magnetic rods 162 are fully enclosed by the tips, or the sheaths, of the tip comb 164 (column 28, lines 57-59). Fritchie also teaches that the magnetic rods 162 together with the tip comb 164 move slowly up and down in the micro-wells, and the magnetic particles are collected onto the walls of the tips, or the sheaths, of the tip comb 164 (column 28, lines 60-63). Fritchie teaches that the magnetic rod 162 together with the tip comb 164, having collected the magnetic particles, can be lifted out of one column of micro-wells and transferred into the next column of micro-wells required by the process, etc (column 28, lines 63-66).
Regarding claim 10, Fritchie teaches that after the magnetic microparticles are incubated in the micro-wells containing the pre-trigger solution, the luminescent material, is released and the quantity of photons emitted is determined by a luminescence reader (column 35, lines 24-28).
Response to Arguments
Applicant's arguments filed 05/22/2026 have been fully considered but they are not persuasive except to the extent expressly indicated below.
Applicant’s arguments on page 4 with respect to the rejection of claims 5-7 under 35 U.S.C. 112(b) as being indefinite have been fully considered and are persuasive. Claims 2-7 have been canceled by Applicant. Accordingly, the rejection of claims 5-7 under 35 U.S.C. 112(b) has been withdrawn.
Applicant’s arguments on page 4 with respect to the rejection of claim 1 under 35 U.S.C. 112(b) as being indefinite have been fully considered and are persuasive. Claim 1 has been amended by Applicant to recite the active steps of "(a) generating magnetic bead immune complexes by reacting i) capture antibodies coupled to magnetic beads, ii) a biological sample comprising a target biological specimen, and iii) detector antibodies coupled to an enzyme, in a reaction chamber", "(d) dispersing the magnetic bead immune complexes in the detection chamber by moving the magnetic beam up within the hollow portion of the washing tip to react the enzyme of the magnetic bead immune complexes with the substrate for a predetermined time to produce an optical material", and "(g) performing an optical inspection on the optical material remaining in the detection chamber", which clarifies the process of analyzing an immune response as recited in the preamble. Accordingly, the prior rejection of claim 1 under 35 U.S.C. 112(b) has been withdrawn.
However, the amendments to claim 1 have necessitated a new ground of rejection under 35 U.S.C. 112(b) (see above claim rejections).
Applicant’s arguments on pages 9-11 with respect to the rejection of claims 1-3 under 35 U.S.C. 102(a)(1)/102(a)(2) as being anticipated by Noh et al. (2019). “Pipetting-based immunoassay for point-of-care testing: Application for detection of the influenza A virus”. Scientific reports, 9(1), 16661, (herein referred to as Noh), have been fully considered and are persuasive. Applicant has amended claim 1 to additionally recite elements that define the target sample being analyzed, as well as elements that recite additional details of the wash step, tip characteristics, and procedure for dispersal and attachment of the magnetic bead immune complexes into and out of various chambers. Claim 1 is no longer anticipated by Noh, and claims 2 and 3 have been canceled. Accordingly, the previous rejection of claims 1-3 under 35 U.S.C. 102(a)(1)/102(a)(2) has been withdrawn. However, Applicant has amended the claims which has necessitated a new ground of rejection under 35 U.S.C. 103 over Fritchie et al. (U.S. Patent No. 8,222,048), (referred to herein as Fritchie), in view of Kim et al. (2017). “Integrated magnetic bead–quantum dot immunoassay for malaria detection”. ACS sensors, 2(6), 766-772. (referred to herein as Kim), (see above rejections).
While amended claim 1 overcome the rejection of claims 1-3 as being 35 U.S.C. 102(a)(1)/102(a)(2) as being anticipated by Noh and this rejection has been withdrawn, Examiner would like to point out a discrepancy in the now moot arguments for documentation purposes. On page 10, Applicant argues that “In contrast, the method of claim 1 recites the steps of physically washing the complexes (Step b) and introducing the washing tip into the detection chamber while the complexes remain securely attached to the outer surface of the washing tip (Step c). By maintaining the magnetic beads captured on the tip during the washing step without dispersing them and dispersing them after they are positioned inside the detection chamber (Step d), the claimed method can prevent the loss of magnetic beads and minimize cross-contamination”. However, the teaching of keeping the beads attached to the washing tip during the washing step without dispersing them is not taught in amended claim one. That teaching is found in newly added claim 9.
Applicant argues on pages 10-12 with respect to the rejection of claims 1-7 under 35 U.S.C. 102 and 35 U.S.C. 103 that “none of the cited references, alone or in combination, discloses or suggests the integrated, automated sequence recited in amended claim 1”. This argument has been fully considered but is not persuasive. Any modification to the statement of the rejection, including reliance on additional prior art, is necessitated by Applicant's amendments to the claims and is made to address the newly added or clarified claim limitations. Applicant argues that “Guckenberger merely isolates cells/DNA and does not teach reacting enzymes with substrates in a detection chamber, nor does Kim teach the use of a hollow washing tip with an internally movable magnetic beam. None of cited references provide any reason to motivate one of ordinary skill in the art to extract disparate mechanical and procedural fragments from the five different cited references to arrive at the method including the steps now recited in claim 1”. The argument regarding Guckenberger is now moot because the rejection of claim 1 (or any other claim) under 35 U.S.C. 103 over Fritchie in view of Kim no longer relies on the teachings of Guckenberbger. Fritchie teaches reacting enzymes with substrates in a detection chamber as well as the use of a hollow washing tip with an internally movable magnetic beam in an automated system.
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, Kim does provide a reason to motivate one of ordinary skill in the art to solve the deficiency of Fritchie by modifying the method to remove the beads prior to optical detection, as Kim teaches that in similar assays removing the magnetic beads from the detection well reduces signal bias and increases signal detection/sensitivity by reducing background noise. Thus, it would have been obvious to one of ordinary skill in the art to combine the teachings of Fritchie and Kim to arrive at the method recited in amended claim 1.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Additionally, Applicant argues on pages 10-12 that “Further, the claimed step of moving the magnetic beam up and down within the washing tip directly inside the detection chamber produces a remarkable, unexpected improvement in assay reproducibility. As described in the present specification, removing the magnetic bead immune complexes right before the optical inspection completely prevents the magnetic beads from absorbing and scattering the optical signal. This specific step effectively eliminates the bias signal (background signal)”. This argument has been fully considered but is not persuasive. It is important to note that Applicant is conflating two separate acts in a way that is not logically consistent. Applicant states that step of moving the magnetic beam up and down within the washing tip directly inside the detection chamber produces a remarkable result, but then describes that it is actually the step of removing the magnetic bead immune complexes right before the optical inspection that leads to the improvement. Moving the magnetic beam up and down and bead removal are not mutually inclusive acts, therefore it is the step of bead removal that results in the claimed remarkable and unexpected improvement.
Applicant further argues that “By employing the claimed method, the coefficient of variation (CV) drastically decreases from 14.4% to an astonishing 4.2%, leading to highly reproducible and accurate quantitative measurements (see the present application specification and FIGS. 27A-27B). Such a dramatic reduction in CV and improvement in signal-to-noise ratio constitute a synergistic effect that could not have been predicted by merely combining the pipetting method of Noh with the bead removal concept of Kim or the hollow head of Guckenberger”
However, as described above, the rejections of claims 1, 8, 10, and 11 no longer rely on the teaching of Noh or Guckenberger. Furthermore, as discussed in the rejection above, teaches Kim teaches that since scattering from the magnetic beads increases the background signal at shorter wavelengths and autofluorescence of the beads increases the background signal, elution of the particles from the complex prior to fluorescent detection significantly improves the sensitivity of the assay, and that based on their previous work, elution improves the signal-to-noise ratio of the assay by 6.7-fold (page 769, column 1, 1st paragraph). Therefore, based on the 6.7-fold improvement in the signal-to-noise ratio taught by Kim, an improvemtn similar to the one shown in the instantly claimed invention could have been predicted by merely combining the teachings Fritchie with the bead removal step of Kim.
Furthermore, it is established in MPEP 2145(II) that prima facie obviousness is not rebutted by merely recognizing additional advantages present but not recognized in the prior art. Therefore, the applicants declaratory evidence alleging remarkable, unexpected improvement in assay reproducibility does not rebut the prima facie case of obviousness presented in the above rejection.
Allowable Subject Matter
The following is a statement of reasons for the indication of allowable subject matter: Regarding claim 9, the prior art does not disclose a wash step method where a hollow tip with a magnetic beam inside adheres magnetic bead immune complexes to the outside of the tip, and the washing proceeds by repeatedly moving the washing tip up and down in the washing chamber containing a washing solution. The prior art discloses wash methods where a hollow tip with a magnetic beam inside attaches and moves magnetic bead immune complexes to a wash chamber, where they are then released from the tip and dispersed into a washing solution.
Examiner proposes incorporation of claim 8 elements into claim 1 to improve the clarity of the claim. Examiner also proposes the incorporation and 9 elements into claim 1 to create a potentially allowable claim. Below is a revised version of claim 1, portions revised by the examiner are underlined or crossed out.
The following claim 1 drafted by the examiner and considered to distinguish patentably over the art of record in this application, is presented to applicant for consideration:
1. (Currently Amended) A method for analyzing immune response using magnetic beads, including steps of:
(a) generating magnetic bead immune complexes by reacting i) capture antibodies coupled to magnetic beads, ii) a biological sample comprising a target biological specimen, and iii) detector antibodies coupled to an enzyme, in a reaction chamber;
(b) introducing a washing tip having a hollow portion into the reaction chamber; and capturing the magnetic bead immune complexes on the outer surface of the washing tip by positioning a magnetic beam inside the hollow portion of the washing tip.
wherein the step of physically washing comprises: moving the washing tip, to which the magnetic bead immune complexes are attached, to a washing chamber; and repeatedly moving the washing tip up and down in the washing chamber containing a washing solution while maintaining the magnetic beam within the hollow portion of the washing tip.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALEXANDER JOSEPH HOFFMAN whose telephone number is (571)272-9080. The examiner can normally be reached 10:00-6:30 M-F.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bao-Thuy Nguyen can be reached at (571) 272-0824. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ALEXANDER J. HOFFMAN/Examiner, Art Unit 1677
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 August 13, 2026
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