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 .
Election/Restrictions
1. Applicant’s election without traverse of Group III, encompassing 9-10, in the reply filed on March 27, 2026 is acknowledged.
2. Claims 1-8 and 11-22 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on March 27, 2026.
3. Claims 9-10 are under examination in the current office action.
Information Disclosure Statement
4. The information disclosure statements (IDSs) filed 05/18/2022 and 01/19/2024 have been considered and the references therein are of record.
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.
5. Claim(s) 9-10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hoshi et al. (US 8,168,188 B1; listed on 05/18/2022 IDS) in view of Harlow et al. (Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory, 1988, pp. 578-582 and 591-593).
Hoshi et al. disclose and claim a method for detecting Alzheimer’s disease in an individual which comprises bringing a biological sample obtained from the individual into contact with an antibody that selectively binds amylospheroid (ASPD) and assaying for the presence or absence of binding to ASPD in the sample (see claim 15 at col. 340. Hoshi teaches that detection of amylospheroid in biological samples using an anti-ASPD antibody can be carried out via conventional immunological assay techniques, such as sandwich assay (col. 18 lines 1-4).
As it pertains to the present claims, Hoshi indicates at column 18, lines 5-11, that in the sandwich assay, biological samples are brought into contact with an anti-amylospheroid antibody of the present invention bound to a solid-phase (bringing a biological sample that may contain ASPD into contact with an antibody (first antibody) that is capable of binding to ASPD and is bound to an insoluble carrier (claim 9, step 1)), which is the capture antibody or “first antibody” of the sandwich. Then, a labeled anti-amylospheroid antibody (i.e., the detection antibody of the sandwich assay) is allowed to react therewith (reacting an anti-ASPD monoclonal antibody (second antibody) with the ASPD that as bound to the first antibody in step (1) (claim 9, step 2)), and signal of a label substance bound to the solid phase is assayed (a label of the second antibody that as bound to the ASPD (as in claim 10)).
Hoshi teaches the anti-ASPD mouse monoclonal antibodies MASD1 (FERM ABP-10392), MASD2 (i.e., mASD2)(FERM ABP-10393), and MASD3 (i.e., mASD3)(FERM ABP-10394) (see paragraph spanning cols. 20-21, and Table 1 at col. 21). Hoshi further teaches that anti-ASPD antibodies of the invention include humanized antibodies, wherein the known monoclonal antibodies are humanized by conventional techniques (col. 11 lines 38-45). Taken together, these teachings provide for a first antibody that is a humanized anti-ASPD monoclonal antibody huASD2, and a second antibody that is a mouse monoclonal anti-ASPD antibody mASD3 or a labeled antibody that is mASD3 with a label as in claim 9.
Accordingly, Hoshi provides for all elements of present claim 9 and the labeled second antibody of claim 10. Hoshi also demonstrates the use of biotin-labeled MASD3 antibody for use in a solid-phase amylospheroid competitive ELISA, in which detection of competition between different ASPD antibodies was performed using peroxidase-labeled avidin D (see Example 4(2) Competitive Test at col. 25). Nevertheless, the reference does not explicitly state that the sandwich assay for detecting ASPD comprises a binding partner of the labeled second antibody, having a reporter linked thereto, as in claim 10.
Hoshi does, however, state at col. 18, lines 16-21, that the disclosed immunological assays, such as the sandwich assay discussed above, can be carried out in accordance with experimental guidebooks such as “Antibodies: A Laboratory Manual” (Ed Harlow et al., Cold Spring Harbor Laboratory, 1988). As taught by Harlow et al., the two-antibody sandwich assay comprises the use of an unlabeled first antibody and a labeled second antibody (pp. 580-581). Harlow teaches that all immunoassays rely on labeled secondary antibodies are secondary reagents for detection, and that these secondary agents can be labeled with biotin. Biotin-coupled reagents, Harlow indicates, usually are detected using labeled streptavidin or avidin. Streptavidin and avidin bind tightly and quickly to biotin, and both can be labeled with iodine or enzymes (see pp. 591-592).
Streptavidin and avidin labeled with iodine or enzymes each meet the limitation of a binding partner (of biotin-labeled secondary antibody) having a reporter (iodine, enzyme) linked thereto as in claim 10.
Therefore, it would have been obvious to one of ordinary skill in the art before the filing date of the claimed invention to have developed an immunoassay for detecting and analyzing amylospheroid in a biological sample according to the teachings of Hoshi and Harlow and thereby arrive at the presently claimed invention. In particular, all of the elements of the presently recited assay method are described, explicitly or implicitly, by Hoshi, as further evidenced by the teachings of Harlow. Given that Hoshi teaches that amylospheroids are neurotoxic, self-aggregated species of amyloid-beta protein that are believed to be the toxic form of amyloid-beta associated with the neuropathology found in the brains of Alzheimer’s disease (AD) patients (see col. 2, lines 43-58), the artisan would have been motivated to have developed an assay to analyze the presence or level or ASPD within a biological sample, such as to aid in the detection of AD in an individual. Given also that Hoshi teaches the anti-ASPD antibodies of the instant claims and their application in conventional sandwich immunoassay techniques (as evidenced by Harlow) for detecting ASPDs, the skilled artisan would have had a reasonable expectation that an immunoassay for analyzing ASPD as claimed could be successfully made and used.
6. Claim(s) 9-10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hoshi et al. (US 8,168,188 B1; listed on 05/18/2022 IDS) and Harlow et al. (1988), and further in view of Suzuki et al. (5,750,349) and Hyman et al. (US 2005/0048539 A1).
The teachings of Hoshi et al. and Harlow et al. are discussed above and provide for the ASPD detection assay method of claims 9-10. However, the prior references do not teach the first antibody can be the monoclonal antibody BAN50a, as in claim 9.
Suzuki et al. teach the monoclonal antibody BAN-50a, which is directed to an N-terminal portion of amyloid-b peptide (Ab1-16), and which can be used in combination with other anti-amyloid antibodies in sandwich immunoassays (see, for instance, col. 4). For example, Suzuki demonstrates the use of BAN-50a in a sandwich enzyme immunoassay (EIA) in which BAN-50a is attached to a solid phase as the primary antibody, and an HRP-labeled BA-27a antibody as the secondary antibody (see Example 10 at col. 37).
Consistent with the teachings of Suzuki, Hyman et al. also teaches that BAN50 can be used as the capture antibody (i.e., the first antibody) in combination with a different HRP-conjugated anti-Ab(1-x) antibody (BNT77) as the detection antibody in a sandwich ELISA (see [0164]).
The prior art discloses of Suzuki and Hyman thus demonstrate that BAN50a is a well-known, reliable monoclonal antibody that can be successfully used as a capture antibody in sandwich immunoassays for the detection of various amyloid-beta species in combination with other anti-amyloid antibodies.
Accordingly, it would have been obvious to one of ordinary skill in the art before the effective filing date of the present invention to have substituted the BAN50a antibody as taught by Suzuki and Hyman for the huASD2 antibody as taught by Hoshi and thereby arrive at the presently claimed detection assay. This is because the artisan has good reason to pursue the known options within his or her technical grasp to obtain predictable results. In the instant case, this amounts to the simple substitution of one known element for another (huASD2 for the anti-amyloid antibody BAN50a) to achieve predictable results.
Conclusion
7. No claims are allowed.
Advisory Information
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/KIMBERLY BALLARD/Primary Examiner, Art Unit 1675
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