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 .
Status of the Claims
Claims 1-16 are pending and are examined herein.
Priority
This application, filed 03/07/2023, claims foreign priority to JAPAN 2022-037188, filed 03/10/2022. This priority is acknowledged and the claims examined herein are treated as having an effective filing date of 03/10/2022.
Information Disclosure Statement
The Information Disclosure Statement filed 03/02/2026 is acknowledged and has been considered.
Withdrawn Rejections/Objections
The rejection of claim 13 under 35 U.S.C. 112(b) is withdrawn in response to Applicant’s amendment.
Amended 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 1-16 are rejected under 35 U.S.C. 103 as being unpatentable over US 6,416,738 B2, “PRETARGETING METHODS AND COMPOUNDS” (filed 04/25/2020, referred to herein as Theodore) as evidenced by Green et al., “A spectrophotometric Assay for Avidin and Biotin Based on Binding of Dyes by Avidin” (published Dec 1965, referred to herein as Green).
Regarding claim 1, if the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. In order words, a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. See MPEP 2111.02 II. In this case, the recitation of “for measuring L-biotin conjugated with an antibody” in claim 1 does not provide any structural significance to the claimed reagent beyond the limitations in the body of the claim.
Regarding claims 1, 3, 4, and 5, Theodore teaches a reagent for measuring biotin (col. 50, lines 61-65) with streptavidin (col. 50, lines 61-65, Figure 3) with the “HABA assay” (col. 69, lines 61-66) using biotin conjugated with an antibody, which uses the azobenzene derivative 4’-hydroxyazobenzene-2-carboxylate as evidenced by Green (Figure 1 Legend, lines 1-3).
Regarding claim 2, Theodore teaches streptavidin made up of D-amino acids (col. 50, lines 51-54), which binds to L-biotin and not D-biotin (col. 51, lines 1-4).
Regarding claims 6 and 7, Theodore teaches measuring biotin concentration with the “HABA assay” (col. 69, lines 61-66, Table 2) comprising mixing the biotinylated sample, the biotin-binding streptavidin, and 4’-hydroxyazobenzene-2-carboxylate, then measuring the absorbance of the sample which is an index of biotin concentration, as evidenced by Green (col. 2, lines 6-14).
Regarding claims 8, 9, 11, and 12, Theodore teaches a method of determining the number of biotins on an antibody with the “HABA assay” (col. 69, lines 61-66, Table 2) comprising mixing the biotinylated sample, the biotin-binding streptavidin, and 4’-hydroxyazobenzene-2-carboxylate, then measuring the absorbance of the sample which is an index of biotin concentration, as evidenced by Green (col. 2, lines 6-14).
Regarding claim 10, Theodore teaches determining the number of biotin molecules per labeled substance by determining the molar ratio of biotin to the labelled substance (“Measured Derivitization (Biotins/Ab)” Table 2).
Regarding claims 13, 14, and 15, Theodore teaches a microparticle with immobilized biotin (col. 81, lines 13-18). Theodore teaches that these particles are used for clearing avidin-containing agents from a sample (col. 81, lines 13-20) by containing a plurality of bound biotin molecules (col. 81, lines 13-20). Theodore teaches the use of the HABA assay to determine the concentration and number of biotin molecules on a polypeptide (col. 76, lines 21-25), which comprises mixing the biotinylated sample, the biotin-binding streptavidin, and 4’-hydroxyazobenzene-2-carboxylate, then measuring the absorbance of the sample which is an index of biotin concentration, as evidenced by Green (col. 2, lines 6-14). Theodore teaches that biotin groups on clearing agents need to be in a predetermined range (col. 103, lines 36-44). Theodore teaches contacting the biotin-labeled clearing agent with the biotin-binding site to immobilize the biotin-binding site (col. 81, lines 13-20).
Regarding claim 16, Theodore teaches the use of biotin-labeled albumin as a clearing agent (col. 102, lines 35-42, “G-HAS-B”).
Theodore does not teach biotin-labeled albumin in solid phase.
However, Theodore does teach that clearing agents, such as biotin-labeled albumin, can be attached to solid microparticles (col. 81, lines 24-30).
It would have been obvious to modify the biotin-labeled albumin clearing agent by binding it to a solid phase microparticle, as taught by Theodore. Doing so would provide to the advantage of localizing “the clearing agent to the RES and liver…to remain in circulation for a time sufficient to perform the clearance function” (col. 83, lines 1-8). One would have an expectation of success because Theodore teaches that biotin-labeled clearance agents, such as albumin, can be attached to microparticles to perform the clearance function.
The examples taught by Theodore do not measure specifically L-biotin in a sample.
However, Theodore further teaches that the embodiments of their invention can be used with L-biotin and that streptavidin formed with D-amino acids (“mirror image streptavidin”, col. 51, lines 12-15) can be used to measure L-biotin (col. 51, lines 1-4).
It would have been obvious to one of ordinary skill to modify the method of measuring D-biotin to measure L-biotin by changing the isoform of the streptavidin as taught by Theodore. Doing so would allow for the measurement of L-biotin in alternative embodiments of the invention. This would be advantageous because embodiments of L-biotin are not sensitive to endogenous D-biotin in samples, as taught by Theodore (col. 50, lines 29-36).
Response to Arguments
Applicant's arguments filed 02/17/2026 have been fully considered but they are not persuasive for the following reasons:
Regarding the remarks on page 7 regarding the rejection of claim 13 under 35 U.S.C. 112(b), the rejection has been withdrawn in response to Applicant’s amendment.
Regarding the remarks on page 8 regarding the rejection of claims 1-16 under 35 U.S.C. 103, Applicant argues that Theodore does not disclose or suggest that L-biotin conjugated to an antibody can be quantified via displacement of an azobenzene derivative.
This argument is not persuasive. Theodore does teach the measurement of biotin attached to an antibody using an azobenzene derivative (col. 69, lines 61-66), as described above in the rejection under 35 U.S.C. 103. Further, the method claim 6 is directed toward a method of measuring L-biotin and is not limited by the recitation of “for measuring L-biotin conjugated with an antibody” in the preamble of reagent claim 1.
Further regarding the remarks on page 8, Applicant argues that the ability of the claimed reagent and method to measure conjugated L-biotin is unexpected.
This argument is not persuasive. As stated above, the method claim 6 is directed toward a method of measuring L-biotin and is not limited by the recitation of “for measuring L-biotin conjugated with an antibody” in the preamble of reagent claim 1.
Further regarding the remarks on page 8, Applicant argues that the cited part of Theodore does not disclose an assay measuring the antibody-binding of L-biotin as claimed.
This argument is not persuasive. Two parts of Theodore were cited regarding claim 12, Table 2 and col. 69 lines 1-6. Table 2, titled “Effect of Lysine Biotinylation on Immunoreactivity” shows “Molar Offering (Biotins/Ab)” and “Measured Derivatization (Biotins/Ab)” which indicates that Theodore did quantitatively measure biotins conjugated to antibodies. Regarding the citation of col. 69 lines 1-6, this was the result of a typo which should have cited col. 69 lines 61-66 further down the column of text. However, the citation of Table 2 alone would be sufficient to indicate the teaching of Theodore.
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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/C.E./Examiner, Art Unit 1677
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 May 27, 2026
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