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 .
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.
Status of the Claims
Claims 1-14 have been amended. Claims 1-14 are pending and examined herein.
Priority
This application, 18/722,357, filed 06/20/2024, is a 371 of PCT/FR2022/052334 filed on 12/13/2022, and claims benefit of FRENCH REPUBLIC FR2114135 filed on 12/21/2021. This priority is acknowledged and the claims examined herein are treated as having an effective filing date of 12/21/2021.
Information Disclosure Statement
The Information Disclosure Statement filed 06/20/2024 is acknowledged and has been considered.
Claim Objections
Claims 2-5, and 8-10 are objected to because of the following informalities:
These claims use periods in the middle of a sentence following the recitation of a step (e.g. “wherein step d. is”). To avoid confusion as to where the sentence ends, the claim language should use parenthesis instead of periods, or neither, to avoid confusion. For example, instead of “c. and d.”, the claims should recite “c) and d)” or “(c ) and (d)”, or “step c and d”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 3, 5 and 10 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1, part c), recites “…attachment of the analyte target;”. The term “analyte target” lacks antecedent basis because it is not recited or defined previously in claim 1, nor does the recited language make evident that “analyte target” is specifically in reference to “target analyte” recited previously in claim 1.
Claim 3 recites “…substantially simultaneously”. The recitation of “substantially” is relative terminology, and as such the claim is indefinite because it is not readily clear compared to what standard is it being compared to be considered substantial.
Claims 5 and 10 recite “…preferably less than 3 minutes”, and “…preferably at least one washing…” respectively. The recitation of “preferably” represents exemplary language that renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention, or represent a description of examples or preferences which can lead to confusion over the intended scope of the claim. See MPEP § 2173.05(d).
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.
Claims 1, 2, 5, and 8-14 are rejected under 35 U.S.C. 103 as being unpatentable over Ward et al. (WO2018140719A1), (herein referred to as Ward), in view of Chiang et al. (US8673576B2), and Daynès et al. (2015). “Fast magnetic field-enhanced linear colloidal agglutination immunoassay”. Analytical chemistry, 87(15), 7583-7587, (herein referred to as Daynès).
Regarding claim 1, Ward teaches a method for detecting analytes in biological samples with magnetic particles, the method comprising the steps of contacting a sample with a magnetic conjugate comprising a magnetic particle and a capture moiety configured to bind the analyte of interest in the sample; contacting the sample with a reporter conjugate comprising a reporter and a reporter binding moiety configured to bind the analyte of interest in the sample; binding the analyte of interest with the capture moiety and the reporter binding moiety; separating the analyte of interest from the sample by applying a magnetic field to the analysis chamber; and detecting the presence, absence, or level of the analyte of interest by detecting the reporter (abstract). Ward teaches that in some embodiments, the reporter may include a metal core (e.g., a metal microparticle or metal nanoparticle) and may include a silica shell ([0011]). Ward teaches applying a first magnetic field, and maintaining it, to combine all of the complexes and form aggregates (Figs. 2-4). In one embodiment, Ward teaches the use of a second magnetic pull down of the magnetic particle after the addition of the reporter conjugate and before detection of the analyte ([0033]). Ward teaches that the capture moiety is an antibody, an antigen-binding fragment, an antigen, a receptor, a ligand, an aptamer, an aptamer receptor, a nucleic acid, or a small molecule ([009]).
Ward teaches a step of concentrating the analyte of interest in the sample by applying a magnetic field to the analysis chamber after contacting the sample with the magnetic conjugate ([00101]). Ward also teaches that in some embodiments, the methods described herein may further include the step of deactivating the magnetic field before contacting the sample with the reporter conjugate ([00101]). Ward also teaches that in some embodiments the sample may be a bodily fluid as described herein, and may include obtaining a bodily fluid sample from a patient ([00111]). In certain embodiments, the methods described herein encompass a sandwich method, a separate addition method, a competitive method, and a tertiary method ([00112]). Ward also teaches that in the presence of analyte, a free antigen can block the binding site on the antibody, thus preventing formation of a complex with the magnet particle and a reporter ([0034]). Ward teaches the detection of CRP using magnetic particles coated with anti-CRP antibodies ([00528]-[00529]). Ward also teaches the use of carboxyl magnetic particles ([00198]).
However, Ward does not teach measuring a first quantity representative of the amount of interfering aggregates in the liquid medium, to identify the presence or absence of said interfering aggregates.
Chiang teaches qualitative and quantitative methods for detecting an analyte or its specific binding partner in solutions, particularly biological samples (column 1, lines 65-67). Chiang teaches that the spectroscopic methods disclosed utilize changes in the spectra of colloidal metal labeled analytes or those of the specific binding partners to determine the presence and/or quantity of an analyte (column 2, lines 1-5). Chiang also teaches the method further comprises obtaining at least one measurement of reagent integrity, wherein the at least one measurement is indicative of non-specific signals (column 9, lines 23-26). “Non-specific signals” refer to absorbance values or changes in absorbance values that are not due to the binding of the first reagent to the second reagent (column 9 lines 30-32). Chiang teaches that in some embodiments, the reaction rate changes at the first wavelength and second wavelength can be measured at different time points, and that the first time point may be within an initial period of mixing the first reagent with the second reagent, and that a second time point may be within a last period of mixing the first reagent with the second reagent (column 2, lines 49-54). Chiang teaches that in other embodiments, a group of reaction rate changes at the first wavelength is determined for a plurality of time points and a group of reaction rate changes at the second wavelength is determined for a plurality of time points, wherein the integration of the first group of reaction rate changes or an integration of the second group of reaction rate changes is indicative of the presence or absence of the complex of the first reagent and the second reagent (column 2, lines 55-63). Chiang teaches that the comparison of the average of the first group of absorbance values to the average of the second group of absorbance values may comprise any suitable mathematical comparison and/or calculation, such as a ratio, difference score, ranking, etc (column 10, lines 3-7). Chiang also teaches that measurements of rates of changes at one or more wavelengths, and optionally their further numerical manipulation by an algorithm, allows for the minimization of nonspecific interference, thus substantially improving the sensitivity of such methods (column 2, lines 9-16).
Daynès teaches a fast magnetic field enhanced colloidal agglutination assay, which is based on the acceleration of the recognition rate between ligands and receptors induced by magnetic forces (abstract). Daynès teaches the setup of a rapid and sensitive homogeneous bioassay applicable to any kind of antigen able to bond simultaneously with two antibodies (page 7583, column 1, 2nd paragraph). Daynès teaches the measurement of C-reactive protein (CRP) as the analyte of interest (page 7583, column 2, 2nd paragraph), and the use of superparamagnetic particles (Carboxyl Adembeads, Ademtech) with polyclonal anti-CRP antibodies covalently immobilized onto the beads (page 7583, column 2, 2nd paragraph). Daynès also teaches the determination of the behavior of magnetic particles under a pulse of magnetic field via the monitoring of the optical response of suspensions containing various amounts of CRP during a magnetization cycle (page 7584, column 1, 5th paragraph). Daynès teaches the quantification of the background OD contribution due to the remaining nonspecific particles aggregation in order to determine a change in optical density in the method of measuring the analyte (page 7585, column 2, 1st paragraph). Daynès also teaches that when the magnetic field is turned on, they systematically observe a sharp decrease of the optical density (OD), and few aggregates are always present within the stock suspension of particles, and this signal may be interpreted as the alignment of those aggregates with external field (page 7584, column 1, 6th paragraph - page 7584, column 2, 1st paragraph). Daynès teaches that they observe that the OD drop is more pronounced when CRP is added in the medium; this could indicate that CRP aggregates particles even before magnetic field is applied, but that this CRP dependent signal is of the same order of magnitude as nonspecific signal due to particles aggregation in stock solution (page 7584, column 2, 1st paragraph). Daynes also teaches that without assistance of the magnetic field, detection of such minute quantities of CRP is impossible (page 7585, column 2, 1st full paragraph). Daynes also teaches that nonspecific aggregates are nearly completely dissociated few seconds only after magnetic field is switched off, but on the other hand, with CRP in the reaction medium, this decrease is no longer observed, and specific antibody-CRP bonds are stable at least several minutes (page 7585, column 1, 1st paragraph).
It would have been obvious to person of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of detecting analytes in biological samples with the two magnetic particles recited by Ward, to take measurements at multiple time points which can represent non-specific/interfering binding, as taught by Chiang, and for these measurements to be of combined analyte/non-specific particles or just the non-specific particles through the application and release of magnetic field, as taught by Daynès, as a matter of applying a known technique to a known method ready for improvement to yield predictable results.
A person of ordinary skill would have been motivated to make this modification because Chiang teaches that their method that measures rates of change (by using multiple measurement timepoints) allows for the minimization of nonspecific interference and improving the sensitivity of such methods, similar to one of the stated goals in the specification of the instantly claimed invention of “ensuring a good analytical sensitivity” ([0016]). Additionally, a person of ordinary skill would have been motivated to incorporate the application and release of a magnetic field to measure non-specific particles as taught by Daynès, because Daynès teaches that using their magnetic pulse method to form aggregates and disassociate them to measure nonspecific binding allows for the detection of minute quantities of analyte that would be otherwise impossible. Furthermore, a person of ordinary skill would have had a reasonable expectation of success in making this modification because of the shared method traits of Ward and Daynès. Ward and Daynès both teach the use of: commercially available carboxyl beads as the magnetic particle, CRP as the analyte measured, and anti-CRP antibodies attached to the particles. The incorporation of the teachings Chiang of measurements at multiple time points which can represent non-specific/interfering binding do not require any physical incorporation and is not limiting, as it merely requires a replication of steps taught by the method of Ward in view of Daynès.
Furthermore, Ward, Chiang, and Daynès, along with the instant application, are in the same field of endeavor of methods of using metal particles to bind and measure an analyte. Like the instantly claimed invention, the method of Ward uses a binding moiety attached to a magnetic particle, which then binds to the analyte of interest, after which a magnetic field is applied to concentrate/aggregate the analyte bound to the particles, then after another magnetic particle (reporter) is used to bind the complexes, representing the base method. Like Ward, Daynès teaches the measurement of an analyte using magnetic particles that bind to the analyte and are manipulated using a magnetic field, but also teaches the measurement of non-specific/interfering binding using this magnetic field manipulation. Combining the magnetic field particle manipulation method to measure non-specific/interfering binding as taught by Daynès, to take the measurements at multiple timepoints to calculate the difference between the timepoints, as taught by Chiang, would have yielded the predictable result of determining not only the amount of non-specific binding but also the amount of analyte binding.
Regarding claim 2, Chiang teaches that the comparison of the average of the first group of absorbance values to the average of the second group of absorbance values may comprise any suitable mathematical comparison and/or calculation, such as a ratio, difference score, ranking, etc. (column 9, lines 66 – column 10, line 3).
It would have been obvious to person of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of detecting analytes in biological samples with two magnetic particles recited by Ward, to calculate the difference between the measurement representing the amount of non-specific/interfering analytes and the later measurement representing the amount of both target analyte and non-specific/interfering analyte, as it would be “obvious to try”. A person of ordinary skill would have been motivated to make this modification in order to have a more sensitive assay for measuring the target analyte, by removing the amounts represented by non-specific binding, e.g. noise. A person of ordinary skill would have had a reasonable expectation of success in making this determination because it requires only a basic mathematical calculation.
Regarding claim 5, Daynès teaches applying a homogeneous magnetic field of 20 mT for only 7 s (abstract). It would have been obvious to person of ordinary skill in the art before the effective filing date of the claimed invention to hold the magnetic field for less than 5 minutes because Daynès demonstrates that magnetic field duration is a result-effective variable, and also that durations far lower than 5 minutes can successfully cause the magnetic particles with attached analyte to aggregate, and Daynès uses a similar overall method as Ward.
Regarding claim 8, Ward teaches that a subject's tonsils are swabbed and 150 μΙ of PBS is then added to a squeezable tube ([00370]). Ward teaches that the swab is then submerged in the PBS solution, and after 1 minute, the swab is pulled midway up the tube and pinched with fingers to extract the liquid from the swab ([00370]).
In another embodiment, Ward teaches the preparation of a spiked serum sample comprising 8 μΙ of 2.5 mg/L CRP dilution and 2 μΙ Normal Serum ([00541]). Ward also teaches 3 μL of the magnetic beads are pre-allocated to each tube, then 3 μL of the sample to be analyzed were added to each tube ([00543]). Ward teaches that after about 30 seconds, add 3 μL of the reporter and then incubate for about 30 minutes ([00543]). Ward teaches that after incubation time, pull down sample tubes on a magnetic stand, rince twice with 100 μL, and resuspend in a final volume of 20 μL TBS ([00544]).
Regarding claim 9, Ward teaches separating the magnetic particle-labeled analyte from the sample by applying a magnetic field to the sample ([0094]).
Regarding claims 10 and 11, Ward teaches that the methods may further include the step of concentrating the analyte of interest in the sample by applying a magnetic field to the analysis chamber after contacting the sample with the magnetic conjugate; removing a volume of the sample from the analysis chamber; and adding a volume of buffer and/or an additional volume of the sample to the analysis chamber ([0014]). Ward teaches that in some embodiments, the present methods reduce signals by controlling solution pH, and the solution pH is controlled by the use of appropriate buffers, which can be specific for the antibodies used, and in some embodiments, Tris/Borate/EDTA buffer and/or buffers with EDTA are utilized; various buffers may be utilized in the invention ([0086]). Ward also recites the use of Reaction Buffer: 5mM potassium phosphate, pH 7.4, 0.5% 20K MW PEG ([00402]). Ward teaches a method of Pre-Incubation of Streptavidin Magnetic Beads with Biotinylated Anti-CRP-C2 Antibody: a. Mix magnetic beads with antibody, which is diluted in conjugate diluent to 1 μΜ, for 5 minutes on rotator. b. Add saturated biotin solution and incubate the combination for 1 minute. c. Place on magnet and pulldown, then wash with Chon Block ([00532]).
Regarding claim 12, Ward teaches that the sample may refer to a solution, suspension, mixture, or undiluted amount of bodily fluid that may or may not include an analyte of interest, and that a sample may include water and/or a buffer ([00148]). Ward also teaches that he term "bodily fluid" may refer to any fluid that can be isolated from the body of an individual and includes, but is not limited to whole blood, plasma, serum ([00149]).
Regarding claim 13, Chiang teaches that in one embodiment the method further comprises obtaining at least one measurement of reagent integrity, wherein the at least one measurement is indicative of non-specific signals (column 3, lines 17-20). Chiang teaches that the measurements of reagent integrity may include determining for an initial time point of mixing the first reagent with the second reagent a transmittance value at a reference wavelength, a maximum absorbance value at a wavelength corresponding to w, or combinations thereof (column 3, lines 20-24). Chiang teaches that such measurements may be compared to pre-determined limit values (column 3, 25-26).
It would have been obvious to person of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of detecting analytes in biological samples with two magnetic particles recited by Ward, to identify interfering/non-specific analytes when the amount exceeds a predefined threshold quantity, as taught by Chiang, as it would be “obvious to try”. Ward teaches detecting the presence, absence, or level of the analyte of interest by detecting the reporter, but it silent as to what levels indicate presence/absence or on the use of predetermined threshold values. A person of ordinary skill would have been motivated to make this modification in order to have a standardized protocol for identifying interfering aggregates in a sample to maintain consistent data. A person of ordinary skill would have had a reasonable expectation of success in making this modification because Chiang demonstrates the use of predetermined threshold limits with regard to analyte measurement, and additionally, the use of such limits is a well-understood, routine, and conventional activity in the field.
Regarding claim 14, Ward teaches device arranged to carry out the method according to claim 1 ([0054]-[0061]).
Claims 3 and 4 are rejected under 35 U.S.C. 103 as being unpatentable over Ward in view of Chiang and Daynès as applied to claims 1, 2, 5, and 8-14 above, and further in view of Rohr et al. (US6294342B1), (herein referred to as Rohr).
The teachings of Ward in view of Chiang and Daynès are incorporated herein.
Regarding claims 3 and 4, Ward in view of Chiang and Daynès teaches all of the limitations of claim 1, and additionally, Ward teaches that the magnetic conjugate (including a capture antibody) may be added simultaneously with a reporter or reporter conjugate (the second particle) ([0096]).
However, Ward in view of Chiang and Daynès does not teach that the steps of negating the first magnetic field and adding in the liquid medium second magnetic particles, and measuring the amount of interfering aggregates are performed simultaneously, or wherein step d. is carried out after negation of the first magnetic field, before adding second magnetic particles in the liquid medium.
Rohr teaches methods utilizing the response of a magnetically responsive reagent to the influence of a magnetic field to qualitatively or quantitatively measure binding between specific binding pair members, where the presence of an analyte mediates whether or not the magnetically responsive reagent binds to a mobile solid phase reagent (abstract). Rohr teaches that by measuring the response to the magnetic field of the magnetically responsive reagent, or that of the mobile solid phase reagent, the presence or amount of analyte contained in a test sample can accurately be determined (abstract). Rohr teaches that the method of the present invention advantageously uses the presence of the analyte to modulate the binding of particles of magnetically responsive reagent to particles of mobile solid phase reagent to form complexes (abstract). Rohr teaches that in an applied magnetic field, the complexes will display magnetic responses that are different from those magnetic responses of the individual particles of magnetically responsive reagent and from those magnetic responses of the individual particles of mobile solid phase reagent (abstract). Rohr teaches that in a variation of this first embodiment, the mobile solid phase reagent can be replaced by a magnetically responsive reagent (column 7, lines 37-39). Rohr teaches that the protocols contemplated the present invention, can be performed in any order of steps or, alternatively, in a simultaneous manner (column 24, line 67 – column 25 line 3). Rohr also specifically teaches in some protocols that the measurement of the second reaction mixture (comprising of the analyte bound to a mobile solid phase reagent and a magnetically responsive reagent) can occur before or after the mixture is exposed to a magnetic field (column 25, lines 5-43; column 26, lines 24-25).
It would have been obvious to person of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of detecting analytes in biological samples with two magnetic particles recited by Ward in view of Chiang and Daynès, to perform the steps of negating the first magnetic field and adding in the liquid medium second magnetic particles, and measuring the amount of interfering aggregates simultaneously, as taught by Rohr, in order to measure analytes present in the solution that did not form first complexes and were not subject to the “pull down” effect of the magnetic field. Daynès teaches that it takes several minutes for the complexes of target analyte bound to magnetic particles to dissociate after the magnetic field is applied. Therefore, performing steps c and d simultaneously would allow for the measurement of second magnetic particle and unbound analyte aggregates suspended in the solution without the first complex in order to increase sensitivity.
Additionally, it would have been obvious to person of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of detecting analytes in biological samples with two magnetic particles recited by Ward in view of Chiang and Daynès, to perform step d after negation of the first magnetic field, before adding second magnetic particles in the liquid medium, as taught by Rohr, in order to have a measurement that represents only the first magnetic particles and any non-specifically bound material in the solution without potential interference due to binding of the second magnetic particles. One of ordinary skill would be motivated to make this modification because it allows for the detection of aggregates prior to the second magnetic particle application and pulldown measure, which allows for measuring initial aggregation. The initial aggregation measurement allows for avoidance of erroneous results by comparison with a predefined sensitivity threshold, increasing accuracy of the assay.
Ward, Chiang, and Daynès, along with the instant application, are in the same field of endeavor of methods of using metal particles to bind and measure an analyte. A person of ordinary skill would have had a reasonable expectation of success in making these modifications because, like the instantly claimed invention, the method of Rohr uses a binding moiety attached to a magnetic particle which then binds to the analyte of interest, a second magnetic particle which binds the analyte, and a magnetic field is applied to concentrate/aggregate the analyte bound to the particles, representing very similar magnetically-assisted binding methods.
Claims 6 and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Ward in view of Chiang and Daynès as applied to claims 1, 2, 5, and 8-14 above, and further in view of Pinchon et al. (2020). “Rapid and specific DNA detection by magnetic field-enhanced agglutination assay”. Talanta, 219, 121344, (published 9 July, 2020), (herein referred to as Pinchon).
The teachings of Ward in view of Chiang and Daynès are incorporated herein.
Regarding claims 6 and 7, Ward in view of Chiang and Daynès teaches all of the limitations of claim 1, and additionally Ward teaches the application of a second magnetic field and the use of a spectrophotometer for analyte detection ([00117]).
However, Ward in view of Chiang and Daynès does not teach the specific magnetization protocol of 8 mT for 1 second, followed by three successive sequences of magnetisations and cuts as follows: 15 mT for 60 seconds, 0 mT for 28 seconds, 8 mT for 1 second, 0 mT for 1 second. Ward in view of Chiang and Daynès also does not teach measuring the first and/or second magnitude from the group consisting of measurement by turbidimetry, measurement by nephelometry and measurement by counting.
Pinchon teaches a method of rapid and specific DNA detection by magnetic field-enhanced agglutination assay (title). Pinchon teaches that their agglutination assay was enhanced using a series of magnetization cycles which improved sensitivity (abstract). Pinchon teaches that their method consists in applying a magnetic field generated by an electromagnet to the reaction medium to accelerate the capture of the target between magnetic particles by a fast-chaining process, and the result of this agglutination performed in a homogeneous phase can then be assayed by a simple turbidimetry readout in less than 5 min (page 1, column 2, 2nd paragraph – page 2, column 1, 1st paragraph). In the method of magnetic field-enhanced agglutination assay, Pinchon teaches that three cycles of magnetization (60 s) and relaxation (30 s) led to the progressive formation of aggregates, a program previously optimized for protein detection, and that the turbidity signal was expressed as the total variation of optical density at 650 nm (Δ OD650nm) measured before and after the three magnetization cycles (page 2, column 2, 2nd paragraph). Pinchon also teaches the use of an electromagnet that provided a 15 mT (mT) field (page 2, column 1, 2nd paragraph). Pinchon also teaches that the total volume effectively used to detect the turbidimetry is in fact as low as 74 μL (page 5, column 1, 1st paragraph).
It would have been obvious to person of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of detecting analytes in biological samples with two magnetic particles recited by Ward in view of Chiang and Daynès, to use the specific magnetization protocol of instant claim 6 recited above, as matter of routine optimization. The MPEP 2144.05 (II) (A) states that “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”).
Pinchon teaches 3 sequences of magnetization at 15 mT, and also demonstrates that the magnetization sequences are a results-effective variable that can change assay sensitivity, and the fact that Daynès uses an entirely different magnetization protocol shows that the techniques is routinely varied in the field of magnetic field-enhanced agglutination assays. Furthermore, the specification of the instantly claimed invention fails to that this magnetization protocol recited produces an unexpected results compared to other ranges; see In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.). Therefore, the selection of such magnetization conditions would be a matter of routine optimization within the level of ordinary skill in the art.
Additionally, it would have been obvious to person of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of detecting analytes in biological samples with two magnetic particles as recited by Ward in view of Chiang and Daynès to measure the first and/or second magnitude by measuring turbidimetry, as taught by Pinchon, because Pinchon teaches that by measuring turbidimetry, the assay can provide a readout in less than 5 minutes, and the turbidimetry was able to be measure using total volumes as low as 74 μL with good sensitivity. A person of ordinary skill would have had a reasonable expectation of success in making this modification because Ward teaches the use of a spectrophotometer for analyte detection, which is the same method used by Pinchon to measure turbidimetry. Furthermore, Ward and Pinchon are in the same field of magnetic field-enhanced agglutination assay to measure an analyte.
Conclusion
For all the reasons discussed above, claims 1-14 are rejected and therefore no claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALEXANDER JOSEPH HOFFMAN whose telephone number is (571)272-9080. The examiner can normally be reached 10:00-6:30 M-F.
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/ALEXANDER J. HOFFMAN/ Examiner, Art Unit 1677
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 August 24, 2026
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