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 .
Priority
The present application was filed on 05/19/2022. Acknowledgment is made of the present application as a proper National Stage (371) entry of PCT/JP2020/041145, filed on 11/04/2020, which claims benefit of the foreign Application No. Japan 2019-209407 filed on 11/20/2019, Japan 2019-216521 filed on 11/29/2019, Japan 2020-042915 filed on 03/12/2020, Japan 2020-100842 filed on 06/10/2020, Japan 2020-138101 filed on 08/18/2020.
Claims status
Claim 1 is amended. Claims 1-6 are pending and examined herein.
Update Objections/Rejections
The rejection of claim 1 under 35 USC 112(b) is withdrawn in view of the amendment of the claim.
The rejection of claims 1, and 4-5 under 35 USC 102 is corrected to 35 USC 102/103.
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) 1, 4-5 is/are rejected under 35 U.S.C. 102 (a)(1) and (a)(2) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Yu (JP2015025787, PTO-892 dated 05/02/2025).
As to claim 1, Yu discloses a method for measuring haptens (see par.1). The method comprises:
an anti-hapten antibody immobilized on a water-insoluble carrier;
and a labeled anti-immunocomplex antibody.
(See paragraph 17: Yu discloses an immunoassay (e.g., ELISA), wherein either an anti-hapten antibody or an anti-immunocomplex antibody is immobilized on a solid phase (e.g., insoluble beads) and label the other with an enzyme or the like. Yu teaches there is no particular limitation on which antibody is labeled.) The teaching of Yu implies the embodiment that an anti-hapten antibody is immobilized on a solid phase and an anti-immunocomplex is labeled.
The method further comprises:
(i) a step of reacting the anti-hapten antibody immobilized on the water-insoluble carrier with a hapten in a solution to be measured,
(ii) a step of reacting the labeled anti-immunocomplex antibody with the hapten-anti- hapten rabbit monoclonal antibody immune complex,
(iii) a step of detecting the signal from the label.
(See paragraph 3: Yu teaches after immobilizing anti-immunocomplex antibody on a solid phase, a sample containing a target hapten and an anti-hapten antibody labeled with an enzyme or the like are added. The anti-immunocomplex antibody selectively binds to an immune complex consisting of hapten and anti-hapten antibody. Therefore, an increase in signal is observed as the amount of hapten contained in the sample increases. See paragraph 22, the signal from the label is measured.
In light of the teaching from paragraph 17, the method in paragraph 3 is reproduced as follow. An anti-hapten antibody is immobilized on a solid phase, sample containing a target hapten and a labeled anti-immunocomplex antibody are added. The reactions between the immobilized anti-hapten antibody with hapten, and between the labeled anti-immunocomplex antibody with the hapten-anti-hapten antibody occur. Thus the teaching of Yu also encompasses the claim limitation.)
Furthermore, Yu teaches that the anti-hapten antibody is a rabbit monoclonal antibody (see par.9, 21, 22, 24, 26 and 28).
While Yu does not explicitly teach the embodiment that an anti-hapten antibody is used as the solid-phase antibody, Yu implies an alternative method to detect a target analyte, wherein the anti-hapten antibody is immobilized on a solid phase and the other (anti-immunocomplex antibody) is labeled (see Yu in par.17 teaches that "either an anti-hapten antibody or an anti-immunocomplex antibody is immobilized on a solid phase and the other is labeled"). Moreover, Yu teaches that there is no particular limitation on which antibody is labeled (see Yu par.17), which implies that which antibody is labeled does not affect the success of the assay.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Yu, by immobilizing an anti-hapten antibody on a solid phase as implied by Yu, as an obvious matter to try, namely choosing from a finite list of suitable, art recognized/known method for detecting a target analyte. Since Yu implies the method of claim 1, one having an ordinary skill in the art would have had a reasonable expectation of success in detecting hapten in the sample. By immobilizing an anti-hapten antibody on a solid phase, the method would improve the sensitivity of the detecting assay by obtaining a higher signal-to-noise ratio because the result is a part of the implementation of the method.
As to claim 4, Yu teaches the invention as discussed above. Yu teaches that the antibody may be labeled with an enzyme such as alkaline phosphatase (see par.17).
As to claim 5, Yu teaches the invention as discussed above. Yu teaches that the hapten is estradiol, or thyroxine (see par.10).
Claim(s) 2 is/are rejected under 35 U.S.C. 103 as being unpatentable over Yu in view of BioChain (ELISA test procedures, 2017, PTO-892 dated 05/02/2025).
As to claim 2, Yu teaches the invention as discussed above. Yu teaches the steps (i), (ii), Although Yu does not mention washing steps between steps (i) and (ii), and between steps (ii) and (iii), Yu discloses that the method is ELISA (see par.3).
BioChain teaches basic principle of sandwich ELISA comprising: coating an antibody specific to an analyte on the solid substrate, reacting the antibody on the solid substrate with an analyte to obtain an analyte-antibody immune complex, reacting the labeled antibody with the analyte-antibody immune complex, and detecting a signal from the labeled (see BioChain Basic Principle of ELISA and Sandwich ELISA Procedure). BioChain teaches that washing steps are applied between the reaction steps to remove any unbound reagents/sample components (see BioChain Basic Principle of ELISA and Sandwich ELISA Procedure). The ELISA is a highly sensitive and specificity test that detects and measures a target analyte (see BioChain page 1 par.1, page 3).
Accordingly, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Yu, by adding washing steps between steps (i), (ii), and (iii) to remove unbound reagents/sample components, so that the assay can achieve accurate results as taught by BioChain (see BioChain page 1 par.1, page 3, Basic Principle of ELISA and Sandwich ELISA Procedure). One having an ordinary skill in the art would have had a reasonable expectation of success in modifying the method of Yu following the teaching of BioChain because Yu and BioChain are directed to an immunoassay for detecting an analyte in the sample, e.g., ELISA, and BioChain teaches that the washing steps are basic steps in ELISA to achieve accurate results of the assay by removing unbound reagents/sample components.
Claim(s) 3 is/are rejected under 35 U.S.C. 103 as being unpatentable over Yu in view of Tatsunari (WO2019098314, PTO-892 dated 05/02/2025).
As to claim 3, Yu teaches the invention as discussed above. Yu further teaches that the anti-immunocomplex antibody can be derived from a mouse (see par.21: disclosing that a mouse anti-immunocomplex antibody obtained by immunizing a mouse with a complex of the above-described anti-E2 rabbit monoclonal antibody and E2). Yu fails to teach that the anti-immunocomplex antibody is a monoclonal antibody.
Tatsunari discloses a method of detecting steroid (i.e., hapten) comprising an anti-steroid antibody immobilized on a solid phase, a labeled secondary antibody that can detect the complex of the anti-steroid antibody and a steroid (see page 5 lines 41-47, lines 59-60, and page 6 lines 1-3). In addition, Tatsunari teaches that the antibody used in the immunological technique may be polyclonal or monoclonal antibodies, preferably a monoclonal antibody (see page 5 lines 4-9). The secondary antibody may be derived from various species such as mouse (see page 5 lines 29-30).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the anti-immunocomplex antibody from mouse as taught by Yu, for the anti-immunocomplex monoclonal antibody from mouse as taught by Tatsunari because Yu is generic about the anti-immunocomplex antibody from mouse despite it is monoclonal or polyclonal, while Tatsunari suggests that it is preferably a monoclonal antibody used in the immunological technique to achieve the high accuracy of the test (see Tatsunari page 1 lines 44-46).
One having an ordinary skill in the art would have had a reasonable expectation of success in combining Yu and Tatsunari because they are analogous to a method of detecting a small molecule, e.g., steroid.
Claim(s) 6 is/are rejected under 35 U.S.C. 103 as being unpatentable over Yu in view of Masashi et al. (JP2006029789, PTO-892 dated 05/02/2025).
As to claim 6, Yu teaches the invention as discussed above. Yu fails to teach that step (i) is carried out in the presence of an absorption antibody.
Masashi discloses an immunoassay reagent (e.g., an antibody) that specifically reacts with a metabolite of a drug to minimize the influence of the drug or drug metabolite in an immunoassay (see page 1 lines 42-48). Masashi teaches that a test sample is treated with an absorption antibody before an immunoassay or simultaneously with an immunoassay. By bringing such an adsorbent into contact with the specimen, the drug metabolite in the specimen reacts with the antibody that reacts specifically with it, and as a result, the free drug metabolites can be reduced. Therefore, immunoassay can be performed in which the adverse effects of drug metabolites coexisting in the specimen are reduced (see page 2 lines 4-15).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Yu, by treating a test sample with an absorption antibody before an immunoassay or simultaneously with an immunoassay as taught by Masashi to reduce the interference in the sample and improve the accuracy of the measurement (e.g., prevent abnormal high value) (see Masashi page 1 lines 20-26).
One having an ordinary skill in the art would have had a reasonable expectation of success in combining Yu and Masashi because Masashi suggests that the absorption antibody reagent can be used in a variety of immunoassay, e.g., a sandwich method, a competition method, an agglutination method, or the like, as long as it uses an antigen-antibody reaction (see page 2 lines 17-19). Moreover, the reagent can be used with a variety of sample derived from a living body include urine, blood, serum, plasma, other body fluids, and tissues (see page 2 lines 21-22). Therefore, the teaching of Masashi can be applied to the method of Yu because Yu teaches an assay using an antigen-antibody reaction to detect an analyte in a sample containing a hapten (see at least Yu par.13 and 17).
Response to Arguments
Arguments filed 10/29/2025 have been fully considered but they are not persuasive.
Applicant argued: “Yu states in paragraph [0017] that "either an anti-hapten antibody or an anti-immunocomplex antibody is immobilized on a solid phase and the other is labeled... There is no explicit disclosure in Yu that an anti-hapten antibody is used as the solid-phase antibody. That is, Yu does not disclose what is presently claimed with sufficient specificity to constitute an anticipation of the claims.”
Examiner agrees that “There is no explicit disclosure in Yu that an anti-hapten antibody is used as the solid-phase antibody.” However, since Yu in paragraph [0017] teaches that "either an anti-hapten antibody or an anti-immunocomplex antibody is immobilized on a solid phase and the other is labeled", Yu implies that the anti-hapten antibody is immobilized on a solid phase and the other (anti-immunocomplex antibody) is labeled.
Applicant argued, in pages 6-7, regarding the results as “remarkable/superior effects, including a higher signal-to-noise (S/N) ratio and improved measurement sensitivity, in the case where an anti-hapten rabbit monoclonal antibody was employed as the solid-phase antibody (Example 3), compared with the case where an anti-immunocomplex antibody was employed as the solid-phase antibody (Comparative Example 1)… the present claims define novel subject matter, are not obvious and are patentable over the cited references, either alone or in combination.”
Examiner respectfully disagrees. Yu in paragraph [0017], teaches that "either an anti-hapten antibody or an anti-immunocomplex antibody is immobilized on a solid phase and the other is labeled." Yu implies that the anti-hapten antibody is immobilized on a solid phase and the other (anti-immunocomplex antibody) is labeled. Therefore, Yu teaches the method of the claim 1. The result is a part of implementation of the method.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
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/CHAU N.B. TRAN/ Examiner, Art Unit 1677
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 March 2, 2026