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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 10/23/2025 has been entered.
Status of the Claims
Claim 1 has been amended. Claim 12 has been added. Claims 1-12 are pending and examined herein.
Priority
This application, 17/764,931, filed on 03/29/2022, is the 371 of PCT/JP2020/033211, filed on 09/02/2020, which claims priority to JAPAN 2019-179385, filed on 09/30/2019. The claims examined herein are treated as having an effective filing date of 09/30/2019.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-11 are rejected under 35 U.S.C. 103 as being unpatentable over US 2019/0271710 A1 (Kolb et al., IDS filed 03/29/2022; herein referred to as Kolb) in view of Luo et al., “Microglial internalization and degradation of pathological tau is enhanced by an anti-tau monoclonal antibody” Sci. Rep. (published 06/09/2015, referred to herein as Luo).
Regarding claim 1, Kolb teaches a tau protein detection method (Abstract, p. 1, para. 0009, lines 1-2) with a plasma specimen (p. 1, para. 0011, line 1-4) collected from a subject (p. 1, para. 0011, lines 1-4) comprising antigen-antibody reactions using two different antibodies that bind to Tau (p. 1, para. 0011, lines 6-9). In this method, the first antibody is immobilized (p. 9, para. 0089, lines 1-5) and the second antibody is labelled without being immobilized (p. 9, para. 0091, lines 1-6). The epitopes recognized by the first (p. 5, para. 0035, lines 2-3, “p217+ tau epitope”) and second antibodies (p. 5, para. 0035, line 5, “116 to 127 of tau protein”) are to amino acids in the intermediate domain. Further, this method comprises subjecting the first antibody to the sample (p. 2, para 0012, lines 3-5, “contacting the sample with a capture antibody”), then the second antibody is subjected to the antigen-antibody reaction (p. 2, para 0012, lines 5-7, “contacting the captured p217+ tau peptides with a detection antibody”).
Regarding claim 2, Kolb discloses that the first antibody recognizes the “p217+ tau epitope” (p. 5, para. 0035, lines 2-3) and the second antibody recognizes “amino acid residues 116 to 127 of tau protein” (p. 2, para 0012, lines 3-5) of tau-441 (p. 8, para 0082, lines 1-4), which are both in the intermediate domain between amino acid residues 103 to 371.
Regarding claim 3, Kolb discloses that the first antibody recognizes the “p217+ tau epitope” (p. 5, para. 0035, lines 2-3) which is within the proline-rich domain between amino acid residues 149-244 of tau-441.
Regarding claim 4, Kolb discloses that the first antibody recognizes the “p217+ tau epitope” (p. 5, para. 0035, lines 2-3) which is within the proline-rich domain between amino acid residues 188-244 of tau-441.
Regarding claim 5, Kolb discloses that the first antibody recognizes a phosphorylated epitope of tau-441 where the phosphorylated amino acid residue is 217 (p. 5, para. 0035, lines 2-3, “p217+ tau epitope”).
Regarding claim 6, Kolb discloses that the first antibody recognizes a phosphorylated epitope of tau-441, where the phosphorylated amino acid residue is 217 (p. 5, para. 0035, lines 2-3, “p217+ tau epitope”).
Regarding claim 7, Kolb discloses an antibody is immobilized on magnetic beads (p. 9, para. 0089, lines 1-5) and an antibody is biotinylated (p. 15, para. 0146, line 4).
Regarding claim 8, Kolb discloses that the second antibody (“detection antibody”) is labelled with enzymes or fluorescent materials (p. 9, para. 0091, lines 1-6).
Regarding claim 9, Kolb discloses that the sample is obtained from a specimen suspected of having a neurodegenerative disorder (p. 4, para 0024, lines 3-5).
Regarding claim 10, Kolb discloses that the sample is obtained from a specimen suspected of having Alzheimer’s disease or frontotemporal dementia (p.4, para. 0024, lines 3-5).
Regarding claim 11, Kolb discloses a method to identify a neurodegenerative disorder (p. 5, para. 0028, line 5, “sample from a subject in need of a diagnosis of tauopathy”) using the previously described method to detect tau (p. 5, para. 0028, line 5) in a blood sample (p. 5, para. 0028, lines 1-2, “the sample is a biological sample, such as blood”).
Kolb does not teach a method for tau detection wherein the second antibody, i.e. the detection antibody, is first reacted with the test specimen, and the first antibody, i.e. the immobilized antibody, is subsequently reacted with the test specimen.
However, Luo teaches a method of detecting tau, “Human tau ELISA” (p. 8, para. 7), wherein the samples are mixed with the detection antibody, then the sample-detection antibody mixture is together added to a well on a plate with the immobilized capture antibody (p. 8, para. 7, lines 2-6). Luo teaches that “samples…were diluted in Superblock blocking buffer and loaded onto the plates together with biotinylated-HT7 antibody” (p. 8, para. 7, lines 4-6). This is interpreted to mean that the HT7 detection antibody was mixed with the sample in blocking buffer before contacting the immobilized antibody on the plate. For comparison and to illustrate the difference, in the “Human Aβ ELISA”, Luo teaches that the samples are loaded into the wells containing the immobilized antibody first, then the detection antibody is added (p. 8, para. 8, line 2 – p. 9, para. 1, line 3).
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 taught by Kolb by first contacting the sample with the detection antibody, then contacting the mixture with the immobilized antibody as taught by Luo. Making this modification is considered to be a simple substitution of known method steps to obtain predictable results (See MPEP 2143(I)(B)). As taught by Luo, mixing a sample containing Tau protein with a detection antibody first, then contacting this mixture with an immobilized capture antibody directed toward a tau phosphorylation site results in predictably being able to detect tau protein.
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Kolb in view of Luo as applied to claim 1 above, and further in view of Blennow et al., “tau Protein in Cerebrospinal Fluid” Mol. And Chem. Neuro. (published December 1995, referred to herein as Blennow) as evidenced by Goedert et al., “Epitope mapping of monoclonal antibodies to the paired helical filaments of Alzheimer's disease: identification of phosphorylation sites in tau protein” Biochem J (published 08/01/1994, referred to herein as Goedert).
Regarding claim 12, as applied above to claim 1, the combination of Kolb and Luo teach the claimed method described in claim 1. Kolb further teaches that the first antibody, i.e. the antibody immobilized on a surface, recognizes a phosphorylated tau protein (Kolb, para. 0011, lines 5-7). Kolb teaches the detection of tau-181 using a second antibody that detects phosphorylation at residue 181 (para. 0243, lines 4-6).
The combined teachings of Kolb and Luo do not teach a method of detecting tau using a first antibody that detects tau phosphorylation at the 181st residue.
However, Blennow teaches a method of detection for tau phosphorylated at the 181st residue using a first, immobilized antibody that recognizes tau-181, “AT270” (p. 235, para. 4, lines 1-6). Blennow incorrectly states that AT270 detects phosphorylation at threonine 231, but it detects phosphorylation at threonine 181, as evidenced by Goedert (Abstract, col. 2, lines 2-5), which is also the cited source in Blennow.
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 phosphorylated tau detection as taught by the combination of Kolb and Luo by substituting the first antibody with the AT270 antibody, as taught by Blennow, which recognizes tau phosphorylated at residue 181. Making this modification is considered to be a simple substitution of known parts to obtain predictable results (See MPEP 2143(I)(B)). As taught by Blennow, the AT270 can be used to predictably capture phosphorylated tau proteins in sandwich ELISA assays, such as the assay taught by the combination of Kolb and Luo.
Response to Arguments
Applicant’s arguments with respect to claims 1-11 rejected under 35 U.S.C. 102 have been considered but are moot because the new ground of rejection based on amendment does not rely on the reference, Kolb, in the prior rejection of record for the teaching or matter specifically challenged in the argument. In this case, Kolb is not relied on for teaching the assay configuration of the second antibody is first reacted with the test specimen, then the first antibody is subsequently reacted with the test specimen.
Conclusion
No claims are allowable.
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/C.E./Examiner, Art Unit 1677
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 December