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 .
Claims 1-4 and 13-23 are pending.
Claim 1 is amended.
Claims 5-12 are cancelled.
Applicant’s election without traverse of Group I (claims 1-12) as well as the species of:
(1) a capture molecule: an antibody or antibody fragment (claims readable on
the elected species: at least Claims 1 and 3);
(2) a labeled binding molecule: an antibody or antibody fragment (claims
readable on the elected species: at least Claims 1 and 4);
(3) an enzyme that catalyzes a reaction to produce ATP: pyruvate phosphate
dikinase (claims readable on the elected species: at least Claims 1 and 5);
(4) a reagent that amplifies ATP: adenylate kinase and pyruvate kinase (claims
readable on the elected species: at least Claims 1 and 9);
(5) a reagent that detects ATP: D-luciferin and luciferase (claims readable on
the elected species: at least Claims 1 and 12); and
(6) an insoluble carrier of the identified material and form: polystyrene plate.
in the reply filed on 01/08/2026 is re-acknowledged.
Claim 13-23 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected group/invention and/or species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 01/08/2026.
Claims 1-4 are under examination on the merits.
Priority
This application is a 371 of PCT/JP2021/019390, filed 05/21/2021, which claims benefit of priority to JAPAN 2020-090398, filed 05/25/2020.Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. Applicant cannot rely upon the certified copy of the foreign priority application to overcome any prior art rejection because a translation of said application has not been made of record in accordance with 37 CFR 1.55. When an English language translation of a non-English language foreign application is required, the translation must be that of the certified copy (of the foreign application as filed) submitted together with a statement that the translation of the certified copy is accurate. See MPEP §§ 215 and 216.
IDS
The information disclosure statement (IDS) filed 05/15/2026 has been considered.
Withdrawn Objections/Rejections
In light of the cancellation of claims 5-12, any objections and/or rejections pertaining solely to claims 5-12 are moot. The rejection of claim 1 and its dependent pending claims 2-4 under 35 USC §112(b) as presented in the office action dated 02/26/2026 are withdrawn as clarified by the amendments to claim 1.
Maintained-Claim Interpretation
Recitation(s) of (target molecule)-(labeled binding molecule)-(capturing molecule) complex) is being interpreted as reciting the elements used to form the complex, not any particular arrangement of those elements (see for example, figure 1 of the instant disclosure noting a different contemplated arrangement of the complex elements as well as the full text of claim 1).
Maintained-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.
Claim(s) 1 and 3-4 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ito et al (Anal Sci. 2003 Jan;19(1):105-9. doi: 10.2116/analsci.19.105; citation 1 under Non-Patent Literature on the IDS dated 11/11/2022) and Hiroshima University (JP 2009060809 A; citation 3 under Foreign Patent Documents on the IDS dated 11/11/2022; Note that a Machine English Translation from Patent Scope is being relied upon, claims 0008 and 0017 of the translation have been provided as screen captures where the translation banner prevents their reference in the Patent Scope Translation).
Regarding claim 1, Ito et al teach an assay where the wells of the microtiter plate were coated with a purified mouse anti-insulin and C-peptide monoclonal antibody. After washing the plate, 50 μl of a standard or sample solution, 50 μl of an FITC-labeled anti-insulin and biotinylated anti-C-peptide monoclonal antibody mixed solution were added to each well. The plates were incubated for 1 h. After washing, 100 μl of pyruvate phosphate dikinase (PPDK) labeled rabbit anti-FITC Fab’ and a biotinylated acetate kinase (AK)-streptavidin complex mixed solution was added and allowed to stand for 1 h (this is held to read upon the recited step 1 where capture molecule-target molecule-labeled-binding molecule complexes are formed (reading on step 1 of claim 1). The microtiter plate was re-washed (note that the washing and re-washing step, by removing unbound detection complex are deemed to read upon step 2 of instant claim 1) and assayed by the simultaneous bioluminescent detection method, where the ATP is determined by the firefly luciferase-luciferin reaction (held to read upon step 5 of instant claim 1). Ito et al succeeded in detecting 8.6 × 10–21 mol/assay for AK and 1.4 × 10–20 mol/assay for PPDK, respectively (see for example, pages 105, 107, and 108 paying attention to figures 1 and 5).
Ito et al do not teach a step of amplifying ATP prior to detection.
However, Hiroshima University teaches a method for amplifying ATP and a reactor for amplifying ATP, where ATP is to be measured using bioluminescence using firefly luciferase (see for example, paragraphs 0001-0002 of the English machine translation obtained from Patent Scope). Hiroshima University further teaches a need to improve sensitivity of ATP detection, which is met by their ATP amplification method which improves ATP detection sensitivity by 10,000 times or more (see for example, paragraphs 0003 and 0008 of the English machine translation obtained from Patent Scope). Hiroshima University goes on to teach that the method for amplifying ATP involves ADP, adenylic acid, and a substrate of the enzyme contacting adenylate kinase and a second enzyme that converts ADP into ATP, the second enzyme being pyruvate kinase (see for example, paragraphs 0001-0003, 0008, 0015-0022 and 0027-0028 of the English machine translation obtained from Patent Scope). Note that Figure 2B at page 17/19 and paragraphs 0028-0032 teach and make obvious amplification of ATP comprising a first step where AMP + ATP are reacted as substrates with adenylate kinase (ADK) to produce 2 ADP and a second step where 2ADP and 2 phosphoenolpyruvate (PEP) are reacted as substrates with pyruvate kinase (PK) to yield 2 ATP (thus amplifying the ATP).
It is noted that the claim is not drafted to preclude the first step and ADP elimination steps preceding the second step of the assay taught by Ito et al (the claim is drafted to comprise the enumerated steps, where ‘comprising’ is open language allowing for additional, unrecited steps/reagents). Therefore, a method comprising both the first and second steps with an intervening step of eliminating the bioluminescent intensity from AK by adding glucose and ADP-dependent hexokinase, which forms AMP from ADP prior to the second step where PPDK converts AMP, phosphoenolpyruvate, and pyrophosphate into ATP is encompassed by the claims as presently drafted. It is further noted that, where Ito et al clearly teach that PPDK generates ATP from AMP, phosphoenolpyruvate, and pyrophosphate, the artisan would have found it obvious to add these reagents into a reaction/assay beginning with the PPDK (second) step of Ito et al in order to generate ATP in the absence of the first step (acetyl phosphate to generate ATP, acetic acid, and light) paired with the intervening elimination step (adding glucose and ADP-dependent hexokinase to form AMP), This would have been obvious to the artisan because Ito et al teach that these reagents are necessary for the reaction of PPDK-generation of ATP to proceed (see for example, page 105 of Ito et al).
It would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of the combined references. The artisan would have been motivated to make and use the invention as claimed because Ito et al teach a detection method comprising a step of producing ATP and then detecting the ATP produced which is generalizable to detect different antigens with a good level of specificity (see the teachings of Ito et al cited above). Where Ito et al teach successful target detection at 8.6 × 10–21 mol/assay for AK and 1.4 × 10–20 mol/assay for PPDK, the artisan would have found it obvious to use an assay using either the AK step alone, the PPDK step alone, or the combination of the AK and PPDK steps as taught by Ito, where selection of only an AK or PPDK step would have been obvious to try in the aim of reducing the total number of steps, reagents, and time involved in the assay. Further, where Ito et al teach an incubation step with FITC-labeled anti-insulin and biotinylated anti-C-peptide monoclonal antibody mixed solution and pyruvate phosphate dikinase (PPDK) labeled rabbit anti-FITC Fab’ and a biotinylated acetate kinase (AK)-streptavidin complex, it would have been obvious to the artisan that precomplexing these components (to form the instantly recited labeled-binding molecule) prior to incubating them with the immobilized antibodies bound to sample (capture molecule bound to target molecule) for predictable use in the method of Ito et al (the precomplexing being an obvious matter of choice yielding no more than predictable results). The artisan would have been motivated to modify the method of Ito et al to comprise the ATP amplification step/method of Hiroshima University to improve the sensitivity of ATP detection as taught by Hiroshima University. The artisan would have found it obvious to affix the ATP amplification enzymes to the secondary binding complexes (called the labeled-binding molecule) for seamless generation, amplification, and detection of ATP with predictable results of amplifying ATP in the presence of the requisite reagents/substrates. The artisan would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references.
Regarding claim 3, as discussed above, the capture molecule in Ito et al is an antibody (more specifically, mouse anti-insulin and C-peptide monoclonal antibodies; see for example, pages 105, 107, and 108 paying attention to figures 1 and 5).
Regarding claim 4, as discussed above, the labeled binding molecule that binds the target molecule (from sample) in Ito et al is an antibody (more specifically, FITC-labeled anti-insulin and biotinylated anti-C-peptide monoclonal antibodies; see for example, pages 105, 107, and 108 paying attention to figures 1 and 5).
Claim(s) 2 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ito et al and Hiroshima University, as applied to claims 1 and 3-4 above, in further view of Stefansson (How to deplete ATP in Solution containing a negatively charged surface protein, Research Gate, published 2013, obtained from: https://www.researchgate.net/post/How-to-deplete-adenosine-triphosphate-ATP-in-solution-containing-a-negatively-charged-surface-protein).
Regarding claim 2, as discussed above, Ito et al in view of Hiroshima University make obvious the assay method of instant claim 1.
Ito et al and Hiroshima University do not teach the method comprising removal of ATP in the specimen prior to formation of the complex of the capture molecule-target molecule-labeled-binding molecule. This is partially because the specimens which Ito et al use as proof of concept appear to be purified specimens (see for example, the reagents section of page 106 of Ito et al), such that there is no need for an ATP removal step.
However, Stefansson teaches that ATP may be successfully depleted in a sample containing a surface expressed protein (without damage to said protein) by using alkaline phosphatase to dephosphorylate ATP (see for example, the entirety of the 1 page reference).
It would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of the combined references The artisan would have been motivated to make and use the invention as claimed because the artisan would have understood that where a sample may comprise a baseline ATP level, said baseline-level of ATP may interfere with the measurement of target accomplished by measuring ATP generated by the labeled-binding molecule and would have found it obvious to look to the prior art for means of depleting ATP in the sample prior to use in the assay according to Ito et al and Hiroshima University. The instant specification notes that the means for removing ATP prior to complex formation is not particularly limited (see for example, paragraph 0035 of the instant specification). Therefore, the method taught by Stefansson would have been expected to function in the method of Ito et al and Hiroshima University to yield predictably results, absent evidence to the contrary. The artisan would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references.
Applicant’s Arguments and Responses
A. Applicant argues for withdrawal of the rejections of claims 1 and 3-4 under Ito et al and Hiroshima University (see pages 6-10 of the remarks dated 05/26/2026).
Response: The claims are not presently drafted to preclude the full method of Ito et al. Even if the claims were to be drafted to preclude the full method of Ito et al, the teachings of Ito further motivate the assay absent the first step and ADP elimination step by teaching the efficacy of the PPDK step, where the artisan would have found it obvious to add phosphoenolpyruvate, pyrophosphate, and AMP to the reaction/assay because Ito et al teach these reagents/substrates are required for the reaction whereby PPDK generates ATP. Therefore, arguments distinguishing the instant claims from the prior art teachings by suggesting that the instant method is superior because it does not require the first step and ADP elimination step of Ito et al are not commensurate in scope with the claims as presently drafted because of the open (comprising) language of the claims. These arguments would further not be considered to make non-obvious the claimed method even if the claimed were amended to preclude the first step and ADP elimination steps of Ito et al because Ito et al teach and motivate beginning with the PPDK step (second step of Ito et al) where the AMP, phosphoenolpyruvate, and pyrophosphate are taught to be required for the reaction and thus would have been obvious to add in order to enable the PPDK-generation of ATP to proceed as taught by Ito et al in the method made obvious by the combination of Ito et al and Hiroshima University as presented in this Office Action. Additionally, where Applicant suggests that the method is nonobvious because it was surprisingly/unexpectedly found that the reactions/assay occurs simultaneously because the D-luciferin/luciferase reaction provides a source of AMP for the PPDK-generation of ATP, it is noted that nowhere in the specification does Applicant teach that this reaction provides the AMP source for the PPDK-generation of ATP (such that step 5 occurs prior to step 3 in time using some undisclosed source of ATP prior to the PPDK-generation step of ATP (instant step 3)). The remarks further do not clearly articulate how this would be reasonably expected or understood to occur in light of the instant disclosure. For these reasons, the rejections of claims 1 and 3-4 over Ito et al and Hiroshima University are maintained at this time.
B. Applicant argues for withdrawal of the rejection of claim 2 over Ito et al, Hiroshima University, and Stefansson (see for example, page 10 of the 05/26/2026 remarks).
Response: Applicant reiterates the rationale argued at point A above which is unpersuasive for the reasons provided in the response to point A above. Applicant further argues that the prior art methods do not make obvious a method without an ADP elimination step or external source of AMP. As noted above, the claims as presently drafted do not preclude either an ADP elimination step or external source of AMP. Applicant again hints at some surprising or unexpected element, but does not clearly present an evidenced showing of any aspect which could be reasonably considered as unexpected or surprising. It is further unclear how the method may proceed without either of an external source of ATP for luciferase to convert to AMP, to then be converted again to ATP by PPDK, said PPDK-generated ATP being then amplified and detected using luciferase. Regarding the argument that the instant method can surprisingly detect even a large amount of ATP in the sample, this is never disclosed as being part of the method, observed from the method, or as being in any way unexpected or surprising. Furthermore, where the prior art combination teaches and makes obvious the steps of a method encompassed by the claims, using reagents encompassed by the claims, the result of detecting a large amount of ATP in a sample would be expected to predictably flow from practicing the method made obvious by the prior art combination. For these reasons, the rejection of claim 2 under 35 USC §103 as presented in this Office Action is maintained at this time.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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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/Ashley Gao/
Examiner, Art Unit 1678
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678
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