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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 02/06/2026 has been entered.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. This application claims benefit of foreign application JAPAN 2020-063156 filed 03/31/2020. Based on the filing receipt, the effective filing date of this application is March 31, 2020 which is the filing date of foreign application JAPAN 2020-063156 from which the benefit of priority is claimed.
Status of Claims
Claims 7-10, 12, and 14 are cancelled.
Claims 1-6, 11, 13, and 15-17 are pending and examined herein.
Withdrawn Rejections
The rejection of claims 1-3, 10, and 16 on the grounds of 35 U.S.C. 102(a)(1) is withdrawn, necessitated by amendment filed 02/06/2026.
The rejection of claims 4-6, 11-15, and 17 on the grounds of 35 U.S.C. 103 is withdrawn, necessitated by amendment filed 02/06/2026.
New rejections are discussed below.
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.
Claim 1 is 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, “carrying out a bound/free separation step”. The term “bound/free separation step” is not defined in the specification. For the purpose of applying prior art, the term will be interpreted as equivalent to separating the amyloid β bound by the antibodies from other substances unbound by the antibodies, based on the applicant’s specification, particularly p. 18.
Claim 16 recites the limitation "The method according to claim 10" in the claim preamble. There is insufficient antecedent basis for this limitation in the claim because claim 10 has been cancelled. For the purpose of applying prior art, the claim will be interpreted to depend on claim 1.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 11 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 11 recites, “The method according to claim 5, comprising the step of detecting binding of said amyloid β in said blood sample and said anti-amyloid β antibody or an antigen-binding fragment thereof”. Claim 11 depends on claim 5, which depends on claim 1. Claim 1 recites, “detecting binding of said amyloid β in said blood sample and said anti-amyloid β antibody or an antigen-binding fragment thereof”. Therefore, claim 11 does not further limit the invention. Applicant may cancel the claim, amend the claim to place the claim in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements.
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.
Claims 1-6, 11, 13, 15-17 are rejected under 35 U.S.C. 103 as being unpatentable over Tokunaga (EP 3373005 A1, published 2018-09-12, cited in PTO-892 dated 04/23/2025) in view of Dhaenens (WO 2015052654 A1, published 2015-04-16) and Westmark, et al. (“Effect of Anticoagulants on Amyloid β-Protein Precursor and Amyloid Beta Levels in Plasma”, published 2013-02-27).
Tokunaga teaches a method for measuring a target protein comprising measuring an amount of the target protein in a blood sample by using an antibody against the target protein in the presence of a polyanionic macromolecule, as in claim 1 (see, e.g., under abstract, and para. [0060], and under “Table 1.”, p. 10-11). Tokunaga teaches, “A concentration of the polyanionic macromolecule in the mixed solution is not particularly limited […] Although the concentration varies depending on the types of samples, it is for example 0.05 mg/mL or higher, but 5.0 mg/mL or lower” (see para. [0047]). 0.05 mg/mL is equal to 0.05 g/L, as in claim 1. Tokunaga teaches a bound/free separation step, as in claim 1 (see, e.g., para. [0058], under steps “(2)” and “(3)”). Tokunaga teaches detecting binding of the target in the blood sample and the anti-target antibody after the bound/free separation step, as in claim 1 (see, e.g., para. [0058], under step “(5)”). Tokunaga teaches the anionic polymer is dextran sulfate sodium, as in claims 2-4 (see, e.g., para. [0060], lines 13-14). Tokunaga teaches the method is a sandwich method, wherein an antigen-binding antibody is immobilized on a solid phase, as in claim 5 (see, e.g., para. [0058], under step “(1)”). It is understood that the magnetic particles are a solid phase. Tokunaga teaches the method comprises detecting binding of the target and the anti-target antibody, as in claim 11 (see, e.g., para. [0058], under step “(5)”). Tokunaga teaches the concentration of the dextran sulfate sodium was 0.77 g/L, as in claims 13 and 15 (see, e.g., under “Table 1.”, p. 10-11). Tokunaga teaches the amount of the target in the blood is quantified, as in claims 16-17 (see, e.g., under “Table 1.”, p. 10-11).
Tokunaga teaches, “blood collection tubes containing a variety of anticoagulants (for example, heparin, EDTA, and citrate) have been used in medical scenes in order to prepare plasmas; however, measurement values of cardiac troponin I in plasmas may vary depending on the types of anticoagulants used for preparing the plasmas” (see, para. [0010]). Tokunaga solves that problem with polyanionic macromolecules (see, e.g., para. [0012]).
Tokunaga fails to teach the target is amyloid β, specifically amyloid β1-40 or amyloid β1-42, as in claims 1-6, 11, 13, and 15-17. Tokunaga fails to teach amyloid β blood sample measurements are dependent on the anticoagulants used during blood collection, in the same manner as the cardiac troponin I assay of Tokunaga.
Dhaenens teaches measuring amyloid β, specifically amyloid β1-42 or amyloid β1-40, in a blood sample with an immunoassay, as in claims 1-6, 11, 13, and 15-17 (see, e.g., p. 15, lines 14-15, and p. 15, lines 3-5).
Westmark teaches that amyloid β blood sample measurements are dependent on the anticoagulants used during blood collection, in the same manner as the cardiac troponin I assay of Tokunaga. Westmark discloses, “We have observed significant differences in Aβ1–42 levels in human plasma dependent on the anticoagulant utilized during blood collection” (see, p. 1, under “Abstract”). Westmark continues, “In conclusion, a robust and reliable blood-based biomarker is needed to assess the progression of amyloidogenic diseases and therapeutic efficacy. Our results demonstrate that blood collection methodology affects downstream ELISA measurements of Aβ1-42” (see p. 3, para. 3).
Tokunaga, Dhaenens, and Westmark are analogous to the field of the claimed invention because they are all in the field of blood-based biomarkers. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to measure the target of Dhaenens with the assay technique of Tokunaga. An artisan would have been motivated to do so because Dhaenens teaches, “Unexpectedly, the inventors have found that plasma Αβ concentrations of several Αβ species in DM1 patients were significantly higher than plasma Αβ concentrations in controls independently of the age or sex of the individuals, and that this variation could be used as a biomarker for the diagnosis and follow-up of patients suffering from DM1” (see, p. 2, lines 10-14). The artisan would have been motivated to use Tokunaga’s assay technique because Westmark teaches that anticoagulants interfere with blood measurements of Aβ peptides and Tokunaga’s assay technique overcomes this problem. An artisan would have had a reasonable expectation of success based on the given disclosures.
Response to Arguments
Rejections under 35 U.S.C. 102
The applicant states that the rejection of claims 1-3, 10, and 16 on the grounds of 35 U.S.C. 102(a)(1) is moot because claim 1 has been amended to include the features of claim 12. The Office agrees and has withdrawn the rejection in response, necessitated by amendments filed 02/06/2026.
Rejections under 35 U.S.C. 103
The applicant has traversed the rejection under 35 U.S.C. 103 of claims 4-6, 11-15, and 17 as being unpatentable over Wang, et al. ("Gold nanoparticle based dot-blot immunoassay for sensitively detecting Alzheimer's disease related β-amyloid peptide", published 2012-07-16) in view of Pesini ("Reliable Measurements of the (β-Amyloid Pool in Blood Could Help in the Early Diagnosis of AD"), Lane, and Tokunaga (EP 3373005 A1). Due to the amendments filed 02/06/2026, that rejection has been withdrawn. The Office will address the features of the arguments that are pertinent to the new rejection.
The applicant argues that Tokunaga is directed at the detection of myocardial troponin I (cTnI), a different biomarker from the present invention. The applicant states that cTnI immunoassay measurements vary depending on the type of sample and the type of anticoagulant used. The applicant argues that the phenomenon of immunoassay measurements varying sample to sample and anticoagulant to anticoagulant is unique to the immunoassay of cTnI. However, as evidenced by Westmark above, the phenomenon of anticoagulants interfering with immunoassays is not unique to cTnI – the phenomenon also affects immunoassays of amyloid β. Therefore, an artisan of ordinary skill in the art would have seen the advantage that the assay technique of Tokunaga presents when measuring amyloid β in blood.
The applicant continues by arguing that the count values of amyloid β do not decrease depending on the blood sample (i.e., serum or EDTA blood plasma). However, the reason for adding the anionic polymer to the amyloid β assay is irrelevant to the claims as written. An artisan would have understood the benefit that the anionic polymer provides in measuring amyloid β in blood, based on Westmark’s teaching that measurement of Aβ1–42 levels in human plasma depend on the anticoagulant used during blood collection and Tokunaga’s teaching that an anionic polymer reduces that interfere (see, Westmark, p. 1, under “Abstract”, and Tokunaga, para. [0012]).
The applicant continues by arguing that the Aβ1-42/Aβ1-40 ratio does not change even if the sampling time is long, by carrying out the antigen-antibody reaction in the presence of an anionic polymer. Whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the “objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support.” In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980) (Claims were directed to a process for removing corrosion at “elevated temperatures” using a certain ion exchange resin (with the exception of claim 8 which recited a temperature in excess of 100°C). Appellant demonstrated unexpected results via comparative tests with the prior art ion exchange resin at 110°C and 130°C. The court affirmed the rejection of claims 1-7 and 9-10 because the term “elevated temperatures” encompassed temperatures as low as 60°C where the prior art ion exchange resin was known to perform well. The rejection of claim 8, directed to a temperature in excess of 100°C, was reversed.). See MPEP 716.02(d). In the claimed invention, the claims do not encompass measuring the Aβ1-42/Aβ1-40 ratio in a blood sample, therefore, the objective evidence of nonobviousness is not commensurate in scope with the claims which the evidence is offered to support.
Conclusion
No claims are allowed.
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/MICHAEL CAMERON SVEIVEN/Examiner, Art Unit 1678
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678