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 1-5, 7-8, and 11-26 are cancelled.
Claims 27-32 are new.
Claim 6 is amended.
Claims 6, 9-10, and 27-32 are pending and under examination on the merits.
Request for Continued Examination
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 10/28/2025 has been entered.
Priority
The claim to priority of the instant application to Japanese Application No. 2018-21159, filed 11/09/2018 and PCT Application No. PCT/JP2019/043799, filed 11/08/2019 is noted. 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.
Withdrawn Rejections
The rejections of claims which were cancelled in the 10/28/2025 claim amendments are withdrawn as moot. The rejections of the claims under 35 USC §103 as presented in the office action dated 05/29/2025 are withdrawn and replaced with the rejections under 35 USC §103 as presented in this Office Action to better account for the newly added limitations and claims resultant from the 10/28/2025 claim amendments.
Newly Necessitated Claim Rejections
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 6, 9-10 and 27-32 is/are rejected under 35 U.S.C. 103 as being obvious over Sekisui Chemical Co Ltd (JP2682697B2; English translation used and provided) in view of Sato et al as cited within Sekisui Chemical Co Ltd (JPS5847256A; English translation used and provided) and Lucas et al (Latex immunoagglutination assay for a vasculitis marker in a microfluidic device using static light scattering detection. Biosens Bioelectron. 2007 Apr 15;22(9-10):2216-22. doi: 10.1016/j.bios.2006.10.029. Epub 2006 Dec 1.).
Regarding claim 6, Sekisui Chemical Co Ltd teach an immunoassay method based on a latex agglutination reaction in which the absorbance is measured with an automatic analyzer, wherein a sensitized latex solution (a reagent for latex turbidimetric immunoassay) and PEGl000 (also called Polyethylene glycol 1000) having an average molecular weight of 1,000 are used (as required by instant claim 6, see for example paragraph 1 of page 2/8). Note that the PEG1000 and/or PEG1000 with sensitized latex solution is an immunoassay reagent as recited in the instant claims (see for example, paragraph 0014 of the instant specification at (4)-(5)). Sekisui Chemical Co Ltd explain that it has been proposed to add PEG to the reaction system for the purpose of improving the measurement sensitivity or promoting the antigen-antibody reaction for visualization of the presence or absence of antibody/antigen in a sample. For example, Sekisui Chemical Co Ltd teach that JPS5847256A (Sato et al) discloses the measurement of an antigen-antibody reaction in which insoluble fine particles carrying an antigen or an antibody are reacted with a corresponding antibody and/or an antigen in a solution, and the reaction mixture is irradiated with light to optically measure (by measurement of transmitted or scattered light) the progress of the reaction (see for example page 1/8). In the method, polyethylene glycol is allowed to coexist in the solution (meeting the limitation of mixing a specimen and immunoassay reagent in instant claim 6). The effect of improving the sensitivity or accelerating the reaction of polyethylene glycol increases as the concentration of polyethylene glycol in the reaction system increases. However, increasing the concentration of polyethylene glycol causes the sample itself to become turbid. The insoluble carrier itself is sensitized with the antigen or antibody and aggregates. The substance to be measured by the invention of Sekisui Chemical Co Ltd is not particularly limited. Generally, any physiologically active substance that can be measured by utilizing the antigen-antibody reaction can be measured. The substance to be measured includes proteins, lipids, etc., for example, various antigens. Examples include antibodies, receptors, enzymes and the like (see for example page 2/8, Comparative Example 7, Figure 9, and Table 10 of Sekisui Chemical Co Ltd).
Sekisui Chemical Co Ltd further teach that in this immunoassay, the concentration of PEG to be present in the reaction system of the antigen-antibody reaction is appropriately selected depending on the molecular weight of PEG and the concentration of additives such as coexisting salts, proteins and saccharides. Generally, the reaction system is prepared so as to contain 0.01 to 3% (W/W), preferably 0.05 to 1.5% (W/W).
Sekisui Chemical Co Ltd do not explicitly teach that the specimen and reagent are mixed in a reaction cuvette with an automatic analyzer.
However, Lucas et al developed a microfluidic immunoassay device using fiber optics to detect static light scattering (SLS) of latex microsphere agglutination. A miniature, portable spectrometer was used to measure forward light scattering intensity collected by the same type of multi-mode fiber. To first show feasibility, anti-mouse IgG were used as target biomolecules and highly carboxylated polystyrene latex microspheres (510 nm) coated with mouse IgG were used as probes. Next, we tested for the vasculitis marker, anti-PR3, using the same type of microspheres coated with PR3 proteins. Lucas et al teach that two-well glass slides Model 48333 (VWR, West Chester, PA) were used as proof of concept to demonstrate SLS for comparison with conventional absorption using a spectrophotometer cuvette (held to be the recited reaction cuvette given the loose definition provided at paragraph 0004 of the instant specification (“[m]ost of currently used automatic analyzers perform measurement by mixing a specimen and a reagent in a transparent plastic or glass container, called a reaction cuvette”]). Lucas et al further teach that the immunoassay was performed in a cuvette (see for example paragraph 1 of section 3.1.1) which is held to make obvious and teach mixing of the specimen (antibody or antigen) with an immunoassay reagent. Reactions were observed and photographed with an inverted microscope (Eclipse TS100, Nikon) and image capture system (Coolsnap K4, Photometrics Inc., Tucson, AZ) using MetaVue software (see for example section 2 and 3).
It would have been prima facie obvious to use the claimed PEG concentrations/molecular weights in a latex agglutination immunoassay using an antibody or antigen (analyte) for optical analysis with an autoanalyzer as described herein because Sekisui Chemical Co Ltd teach that this is successful pointing directly to the claimed PEG parameters for improving sensitivity. Moreover, Sekisui Chemical Co Ltd consistently and expressly state that the PEG parameters (concentration and molecular weight) are variables which would be obvious to vary as part of routine optimization of the method according to the desired use/agents involved (see reference in its entirety). See MPEP § 2144.05. Therefore, the artisan would have been motivated to use PEG1000 at the claimed concentrations in the latex agglutination immunoassay to optimize the assay for sensitivity while decreasing off target turbidity/non-specific findings because Sekisui Chemical Co Ltd teach that this is successful for a wide variety or analytes (antigens/antibodies), as discussed above. One of ordinary skill in the art would have been motivated to adapt the assay of Sekisui Chemical Co Ltd to use a reaction cuvette in/with an automatic analyzer for mixing/reacting the specimen with the latex immunoassay reagent because Lucas et al teach that this is successful, cost effective, small in size, re-usable with simple rinsing, and is more adaptable to an automated lab environment, as discussed above. The artisan would have had a reasonable expectation of success since Sekisui Chemical Co Ltd teach that a PEG concentration within 0.01% (W/W) and 3% (W/W) would provide success (see Sekisui Chemical Co Ltd generally, paying attention to Comparative Example 7, Figure 9, and Table 10) and because Lucas teaches that no false negatives or positives were observed and their optical detection system works without any fluorescence or chemiluminescence markers (see for example the abstract and final paragraph of section 1.2).
Regarding claim 9, as discussed above, Sekisui Chemical Co Ltd teaches a latex agglutination assay which uses Polyethylene glycol 1000 as required by instant claim 9.
Regarding claim 10, as discussed above, Sekisui Chemical Co Ltd teaches a latex agglutination assay which is a latex turbidimetric immunoassay as required by instant claim 10.
Regarding claim 27, as discussed above, Sekisui Chemical Co Ltd teaches a latex agglutination assay according to instant claim 6, which uses Polyethylene glycol 1000 (having an average molecular weight of 1,000).
Regarding claim 28, as discussed above, Sekisui Chemical Co Ltd teaches a latex agglutination assay according to instant claim 9, which uses Polyethylene glycol 1000 (having an average molecular weight of 1,000).
Regarding 29, as discussed above, Sekisui Chemical Co Ltd teaches a latex agglutination assay according to instant claim 10, which uses Polyethylene glycol 1000 (having an average molecular weight of 1,000).
Regarding claim 30, as discussed above, Sekisui Chemical Co Ltd teaches a latex agglutination assay according to instant claim 6. Sekisui Chemical Co Ltd further teaches that it is known in the art that polyethylene is used as an aggregating promoter in reactions and that [the polyethylene] glycol which may be effectively used may have an average molecular weight of 1,000 to 20,000 (citing and incorporating by reference JP-A-63-45066); thus Sekisui Chemical Co Ltd propose to use polyethylene glycol in the reaction system of the antigen-antibody reaction, but the molecular weight is 20,000 or less (see for example, page 2/8). Thus, Sekisui Chemical Co Ltd effectively teaches and suggests use of PEG having a molecular weight range of 1,000-20,000, making obvious the claimed range of 1,900-2,100 for use in the assay.
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 Sekisui Chemical Co Ltd, Sato et al, and Lucas et al. The artisan would have been motivated to make and use the invention as claimed because Sekisui Chemical Co Ltd teach that this range of PEG is effective for use in a latex agglutination assay. The artisan would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references.
Regarding claim 31, as discussed above, Sekisui Chemical Co Ltd teaches a latex agglutination assay according to instant claim 9. Sekisui Chemical Co Ltd further teaches that it is known in the art that polyethylene is used as an aggregating promoter in reactions and that [the polyethylene] glycol which may be effectively used may have an average molecular weight of 1,000 to 20,000 (citing and incorporating by reference JP-A-63-45066); thus Sekisui Chemical Co Ltd propose to use polyethylene glycol in the reaction system of the antigen-antibody reaction, but the molecular weight is 20,000 or less (see for example, page 2/8). Thus, Sekisui Chemical Co Ltd effectively teaches and suggests use of PEG having a molecular weight range of 1,000-20,000, making obvious the claimed range of 1,900-2,100 for use in the assay.
Regarding claim 32, as discussed above, Sekisui Chemical Co Ltd teaches a latex agglutination assay according to instant claim 10. Sekisui Chemical Co Ltd further teaches that it is known in the art that polyethylene is used as an aggregating promoter in reactions and that [the polyethylene] glycol which may be effectively used may have an average molecular weight of 1,000 to 20,000 (citing and incorporating by reference JP-A-63-45066); thus Sekisui Chemical Co Ltd propose to use polyethylene glycol in the reaction system of the antigen-antibody reaction, but the molecular weight is 20,000 or less (see for example, page 2/8). Thus, Sekisui Chemical Co Ltd effectively teaches and suggests use of PEG having a molecular weight range of 1,000-20,000, making obvious the claimed range of 1,900-2,100 for use in the assay.
Applicant’s Arguments and Responses:
A. Applicant states that they do not concede that a prima facie case of obviousness has been made with respect to the rejections over Sekisui Chemical Co Ltd (JP2682697B2; English translation used and provided) in view of Sato et al as cited within Sekisui Chemical Co Ltd (JPS5847256A; English translation used and provided) and Lucas et al (Latex immunoagglutination assay for a vasculitis marker in a microfluidic device using static light scattering detection. Biosens Bioelectron. 2007 Apr 15;22(9-10):2216-22. doi: 10.1016/j.bios.2006.10.029. Epub 2006 Dec 1.) (see page 1 of the remarks dated 10/28/2025).
Response: This is not an argument which articulates deficiencies with the rejections of record. Therefore, this position is noted, but is not deemed persuasive to overcome the rejections of record.
B. Applicant alleges surprising results, further referencing the Declaration dated 10/28/2025, which Applicant asserts overcomes the rejections of record under 35 USC §103 (see pages 1-3 of the remarks dated 10/28/2025 and pages 5-7 of the declaration dated 10/28/2025).
Response: The declaration has been considered. It is noted that the affiant is co-inventor. Affiant substantively begins the discussion of surprising results at page 5 of the Declaration dated 10/28/2025. Affiant notes that the closest prior art (Sekisui Chemical Co Ltd.) and the instant disclosure use and measure different substances (HBs-positive or normal rabbit serum or D-dimer, respectively). However, the test results used to support a showing of surprising results must include results of the test performed on the invention as claimed and on the closest prior art. Here, the experimental conditions are not substantially analogous because results of experiments measuring D-dimer are not readily and reliably compared to the prior art examples conducted with HBs-positive or normal rabbit serum. Rather than offering a comparable benchmark for precision, it is very possible that rabbit serum is merely more difficult to precisely measure such that comparison to the instant results using D-dimer is like comparing apples and oranges. The burden to sufficiently support and articulate an argument of surprising results in rebuttal of obviousness-type rejections (under 35 USC §103) rests upon Applicant and it is submitted that this burden has not been met because the data Applicant points to does not clearly show that the reproducibility of Applicant’s method would not have been present in the prior art method.
Where sufficient data and argument for comparison of the instant method and the prior art method is unavailable for a decision based upon evidence of surprising results, the surviving portion of the argument is that the prior art fails to appreciate a property (reproducibility of measurements) associated with the claimed range of PEG.
The MPEP provides that:
"[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). In In re Crish, 393 F.3d 1253, 1258, 73 USPQ2d 1364, 1368 (Fed. Cir. 2004), the court held that the claimed promoter sequence obtained by sequencing a prior art plasmid that was not previously sequenced was anticipated by the prior art plasmid which necessarily possessed the same DNA sequence as the claimed oligonucleotides. The court stated that "just as the discovery of properties of a known material does not make it novel, the identification and characterization of a prior art material also does not make it novel." Id. See also MPEP 2112(I) with regard to inherency and product-by-process claims and MPEP § 2141.02 with regard to inherency and rejections under 35 U.S.C. 103,”
(see MPEP 2112(I)).
For these reasons, the rejections of record, as they appear in this Office Action, are maintained at this time.
Conclusion
No claim is allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
JP2013140035A (as cited in the 06/04/2021 IDS) teaches an immunoassay latex agglutination method using PEG an automatic analyzers.
JP2001330615A (as cited in the 06/04/2021 IDS) provides an immunoassay reagent, capable of enhancing the sensitivity of conventional immunoassay method and capable of widely adapting a latex agglutination method to a low molecular weight substance which has been difficult for adaptation heretofore, which includes PEG at a weight of 5,000,000 or less.
JP2000258419A (as cited in the 06/04/2021 IDS) teach an immunoassay reagent and method using an antibody-antigen reaction and latex agglutination/hemagglutination, wherein PEG at a weight of 1,000-500,000 is used to promote agglutination with optical detection using an automatic analyzer.
CN104535761A (as cited on the 12/29/2023 IDS) teaches the use of PEG300 (PEG at a molecular weight of 300) at a concentration of 0.1%-2% related to a latex microsphere enhanced immunoturbidimetry and an application thereof, wherein the latex microsphere reagent has the advantages that the sensitivity and detection range are obviously improved and the hyperbranched polyglycerol modified latex microsphere enhanced immunoturbidimetry has excellent performances of relevance, stability and repeatability.
US20160195522A1 provides a particle enhanced agglutination immunoassay including the steps of: mixing a sample solution containing an analyte with a solution containing insoluble carrier particles carrying a binding partner or binding partners for the analyte to prepare a mixed solution; determining a variation (i) in intensity of light scattered from the mixed solution based on a difference in intensity of scattered light between first and second time points; determining a variation (ii) in absorbance of the mixed solution based on a difference in absorbance between third and fourth time points; and correlating the determined variation (i) in intensity of scattered light and the determined variation (ii) in absorbance with an amount of the analyte present in the sample using a calibration curve plotted based on the variation in intensity of scattered light and a calibration curve plotted based on the variation in absorbance. The present invention employs measurements of the intensity of scattered light and the absorbance in combination for a single assay, and thus provides a particle enhanced agglutination immunoassay which achieves higher sensitivity and a wider dynamic range than conventional assays.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ASHLEY GAO whose telephone number is (571) 272-5695. The examiner can normally be reached on M-F 9:00 am - 6:00 pm EST.
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/Ashley Gao/
Examiner, Art Unit 1678
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678