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 01/07/2021. Acknowledgment is made of the present application as a proper National Stage (371) entry of PCT/JP2019/029353, filed on 07/26/2019, which claims benefit of the foreign Application No. Japan 2018-141178, filed on 07/27/2018.
Claim status
Claims 1, 4-5, 8 and 21-25 are pending. Claims 2-3, 6-7, 9-20, and 26 are canceled. Claims 1, 4, 21-23, and 25 are withdrawn. Claims 5, 8, and 24 are examined.
Objections/Rejections status
The rejection of claim 26 under 35 U.S.C. 112(d) is withdrawn in view of the cancelation of the claim.
The rejection of claims 5, 8-9, 20, 24 and 26 under 35 U.S.C. 112(a) written description is withdrawn in view of the persuasive argument.
The rejection of claims 9, 20, and 26 under 35 U.S.C. 103 is withdrawn in view of the cancelation of the claims.
The rejection of claims 5, 8, and 24 under 35 USC 103 is maintained.
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) 5, 8, and 24 is/are rejected under 35 U.S.C. 103 as being unpatentable over Adachi et al. (Enzyme immunoassay system for estimating the ultrastructure of (1,6)-branched (1,3)- β-glucans, Carbohydrate Polymers 39 (1999) 225-229, see IDS submitted in 03/27/2024, PTO-892 dated 05/15/2024), in view of Torosantucci et al. (Protection by Anti-b-Glucan Antibodies Is Associated with Restricted b-1,3 Glucan Binding Specificity and Inhibition of Fungal Growth and Adherence, PlosOne, vol.4, issue 4 e5392, 2009, PTO-890 dated 10/01/2025) and Tanaka (JP 07128337, PTO-892 dated 10/21/2024).
For claims 5, 8, Adachi discloses an enzyme immunoassay system for detecting branched (1,3)-β-glucan (see Abstract). The detection method comprises:
a solid phase on which a first antibody against (1,3)-β-glucan is immobilized (see section 2.5 on page 226: a step of capturing glucan by an immobilized anti-glucan antibody in a microwell plate (i.e. antibody on a solid phase);
an alkali pretreatment solution for the biological sample (see section 2.3 on page 226: before an enzyme immunoassay is processed, incubating glucan with 0.5M NaOH to change the conformation of glucan);
wherein pH of the alkali pretreatment solution for the biological sample is 11 or more (see section 2.3 on page 226: before an enzyme immunoassay is processed, incubating glucan with 0.5M NaOH which is a strong alkali solution (pH is 13.7)).
Adachi further teaches a solution for neutralization of the alkali pretreatment solution for the biological sample (see section 2.3 page 226: 0.5M HCl and 50mM Tris-HCl). This anticipates claim 8.
Adachi further teaches (1,3)- β -D-glucan is (1,3)- β -D-glucan present on a cell wall of Candida fungus (see page 228 col.1 par.2).
Adachi does not teach “the biological sample is blood, plasma or serum of a subject suspected of having deep mycosis caused by Aspergillus fungus or Candida fungus” or “the immunoassay method can detect 6 pg/mL of the (1,3)-p-D-glucan contained in the biological sample”. However, it is noted that the sample is not normally part of a kit, and the limitation regarding the sample is considered to be an intended use of the kit. Similarly, the limitation regarding the ability of the kit to detect (1,3) -β -D-glucan at 6pg/ml describes what the kit can do, not what the components of the kit are, because it does not impart any additional component of the kit. Thus, these limitations do not further limit the kit.
Adachi does not teach a kit and a monoclonal antibody to laminariheptaose.
Torosantucci discloses an immunoassay to support the binding of monoclonal antibody (MAb) to a variety of beta 1,3 glucan linked glucose sequences from laminaritriose to laminariheptaose (see page 13 col.2 par.1, see Fig.3B page 6: binding of the IgG mAb to a highly branched glucan with mixed beta 1,3- and beta 1,6-linked components was almost abolished in the presence of laminarin and strongly inhibited by beta 1,3-linked oligosaccharides which are laminaritriose to laminariheptaose). The detection of the complex of beta 1,3 glucan and Mab can be done by labeled Mabs (see page 2 col.2 par.3, see Fig.1: gold immunolabelling for both IgG- and IgM-reactive antibody).
Torosantucci also supports the presence of laminarin antigens, also called (1,3) -β -D-glucan, on the cell wall of Candida albicans or Aspergillus fumigatus. Laminarins are major fungal pathogens (see Abstract). Fungal cells release abundant beta-glucan during their growth in vitro and in vivo, so that beta-glucan detection in patients’ serum is valued as a diagnostic marker of invasive fungal infections (see page 6 col.1-2).
Tanaka teaches a kit for measuring (1,3) -β-D-glucan in a biological sample, particularly blood (see par.1, par.3 and par.25), wherein the kit comprises a pretreatment agent, an antigen-binding reagent, reaction reagents and the like (see par.25).
The pretreatment agent in the kit is an alkaline solution (see par.16: potassium hydroxide (KOH) and sodium hydroxide (NaOH)). The strong alkaline solution is used for changing the conformation of glucan (see par.12).
The kit is used to detect β-glucan in the blood of a subject (see par.3). Tanaka also teaches that the kit is useful for early diagnosis of fungal infections, particularly deep fungal infections (see par.24-25).
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 Adachi, replacing the polyclonal antibody taught by Adachi with the monoclonal antibody that can bind to laminariheptaose as taught by Torosantucci because the antibodies of Adachi and Torosantucci are functionally equivalent in terms of binding to (1,3) β-D-glucan antigen. It is obvious to one of ordinary skill in the art to select the detecting antibody according to the user preference. By doing that, the modified method of Adachi can be used to diagnose invasive fungal infections in patients’ serum caused by laminarin (see Torosantucci page 6 col.1-2).
Moreover, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to make a measurement kit for detecting (1,3) -β-D-glucan in a biological sample by combining the components from the modified method of Adachi for the benefit of fast testing because the kit supplies a ready to use components for the test (see Tanaka par.24-25 teaches that the kit for detecting (1,3) -β-D-glucan in a biological sample is useful for early diagnosis of fungal infections and the kit comprises the pretreatment agent, detecting agents, and solutions used for the test). Accordingly, the kit of the modified Adachi includes: a solid phase on which a first monoclonal antibody against laminariheptaose is immobilized, an alkali pretreatment solution with a pH of 11 or more, and a solution for neutralization of the alkali pretreatment solution.
One having ordinary skill in the art would have had a reasonable expectation of success in the modification because Adachi and Tanaka are directed to an antigen-ligand based immunoassay to detect β-d-glucan in the sample, wherein the sample is pretreated with an alkaline solution and then neutralized before being detected. Torosantucci provides an alternative antigen-binding reagent that can substitute for the antibody against (1,3) -β-D-glucan taught by Adachi to detect (1,3) -β-D-glucan of interest. This substitution would result in a predictable outcome because the detecting reagents of Adachi and Torosantucci are all working in an immunoassay.
Since the combined prior arts disclose all the components of the claimed kit, it can inherently perform the claimed function, which detects 6 pg/ml of the (1,3)-β-d-glucan contained in the sample.
For claim 24, Adachi, Torosantucci and Tanaka teach the invention as discussed above. Adachi teaches that the alkali solution is 0.5M NaOH, which has pH 13.69. Tanaka teaches that the sample is pretreated under strongly alkaline condition, e.g., 0.06M KOH, which the pH is 12.78. The teaching of Tanaka falls into the claimed pH range, that is 11-12.9.
While Tanaka and Adachi do not specifically teach the same pH value of the alkaline solution, they do suggest a strong alkaline solution with varying pH value. Although the pH of Adachi and Tanaka is not the same, the methods of Adachi and Tanaka still work for measuring the (1,3)-β-d-glucan in the blood samples such as plasma, or serum.
It has long been settled to be no more than routine experimentation for one of ordinary skill in the art to discover an optimum value of a result effective variable. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation." Application of Aller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). "No invention is involved in discovering optimum ranges of a process by routine experimentation." Id. at 458, 105 USPQ at 236-237. The "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." Application of Boesch, 617 F.2d 272, 276, 205 USPQ 215, 218-219 (C.C.P.A. 1980).
Therefore, it would have been obvious for one of ordinary skill to discover the optimum workable ranges of the pH of the alkaline solution for the method of detecting (1,3)-β-d-glucan in the blood samples by normal optimization procedures known in the art. One of ordinary skill in the art could have pursued the known potential solutions (e.g., a strong alkaline solution, pH 12.78 or pH 13.69) with a reasonable expectation of success in measuring the (1,3)-β-d-glucan in the blood samples.
Response to Arguments
Applicant’s arguments, see Remarks, filed 12/29/2025, with respect to the rejection under 35 U.S.C 103 have been fully considered.
Applicant argued on page 6 paragraphs 2-3 that the samples of Torosantucci are not subjected to alkaline treatment, so the anti-beta-glucan monoclonal antibody of Torosantucci et al. is understood to be an antibody that binds to beta-glucan with its natural conformation. Therefore, one of ordinary skill in the art would understand that the anti-beta-glucan monoclonal antibody of Torosantucci et al. cannot bind to alkaline-treated beta-glucan. Therefore, one of ordinary skill in the art would not consider employing the monoclonal antibody of Torosantucci et al. that binds to laminariheptaose in the ELISA method of Adachi et al.
These arguments are not persuasive. Torosantucci also shows that the IgG anti-β1,3-glucan mAb can also bind to beta-glucan after treatment in supporting information Figure S1. Therefore, Torosantucci supports the anti-beta-glucan monoclonal antibody binding to treated beta glucan (see page 15 col.1 par.4).
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One of ordinary skill in the art would consider employing the monoclonal antibody of Torosantucci et al. that binds to laminariheptaose in the ELISA method of Adachi et al. with a reasonable expectation of success because the antibody can detect the treated beta-glucan.
Applicant argued on page 6 paragraph 5 and page 7 paragraph 2 that Adachi et al. teach away from employing a monoclonal antibody in the EIA of Adachi et al. because monoclonal antibodies are in most cases less sensitive than polyclonal antibodies. Thus, one of ordinary skill in the art would also be taught away from employing the monoclonal antibody of Torosantucci et al. in the EIA of Adachi et al. because monoclonal antibodies are in most cases less sensitive than polyclonal antibodies.
This argument is not persuasive. It is obvious to one of ordinary skill in the art to select the detecting antibody according to the user preference. Since the antibodies of Adachi and Torosantucci are functionally equivalent in terms of binding to (1,3) β-D-glucan antigen, it is an obvious matter to try, namely choosing from a finite list of suitable antibodies for detecting an analyte of interest. Moreover, monoclonal antibodies offer high specificity and consistency (see Torosantucci page 10 col.1 par.2: disclosing that the IgG mAb had a quite selective specificity for beta 1,3- linked glucose sequences). Thus, using monoclonal antibodies enables precise target recognition in various assays.
Applicant argued on page 8 paragraphs 1-2 that even if one of ordinary skill in the art trying to improve the Limulus assay of Tanaka '337 were motivated to employ the enzyme immunoassay (EIA) of Adachi et al. and employ the monoclonal antibody of Torosantucci et al., one of ordinary skill in the art would still not arrive at the claimed invention.
This argument is not persuasive. The motivation to employ the enzyme immunoassay (EIA) of Adachi et al. and employ the monoclonal antibody of Torosantucci et al. is not for improving the Limulus assay of Tanaka '337. Examiner relies on Adachi for the teaching of the immunoassay using antibody to detect (1,3) beta-glucan in a sample, wherein the sample is treated with alkali solution. Examiner relies on Tanaka '337 for the teaching of the kit to detect (1,3) beta-glucan in a sample, comprising the pretreatment agent, detecting reagents, standard reagent, reaction reagent etc. so that the method for measuring beta-glucan can be readily processed (see Tanaka par.24-25). It would have been obvious to learn from Tanaka '337, making a kit for detecting (1,3) -β-D-glucan in a sample comprising a set of components necessary for doing the immunoassay taught by Adachi for fast testing because the kit supplies a ready to use components for the test. Examiner relies on Torosantucci for the teaching of the alternative detecting agent that can replace the detecting agent in Adachi because they are antibodies that can detect (1,3) beta-glucan. It is obvious to one of ordinary skill in the art to select the detecting agent according to the analyte of interest, or the user preference. One of ordinary skill in the art would arrive at the claimed invention if he wanted to detect laminariheptaose in the sample because the monoclonal antibodies of Torosantucci can bind to laminariheptaose.
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.
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/CHAU N.B. TRAN/Examiner, Art Unit 1677
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 September 8, 2026
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