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
Applicant’s election without traverse of Group I (claims 1 and ) in the reply filed on 7/8/26 is acknowledged.
Claims 2-18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 2 is rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea (a mathematical equation) without significantly more. The claim(s) recite(s) that the polarization anisotropy is determined by the recited equation 1. This judicial exception is not integrated into a practical application because the steps of preparing, mixing, and determining the presence or absence, or concentration of the target substance from polarization anisotropy are data gathering steps. Data gathering steps required to use the correlation do not add a meaningful limitation to the method as they are insignificant extra-solution activity. Moreover, the claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the additional elements of preparing, mixing, and determining the presence or absence, or concentration of the target substance from polarization anisotropy, when considered separately and in combination, they do not add significantly more (also known as an “inventive concept”) to the exception. These additional limitations only perform the assay using polarization anisotropy and a two particle system that each bind the target substance and with one particle being larger than the other are well-understood, routine, and conventional, and such is exemplified in the prior art below. Examiner further notes that the assay limitations are broad in that a “first particle that specifically binds to the target substance” encompasses a first particle as described by Applicant in the specification and any equivalents, including an antibody labeled with a well-known label such as a fluorophore or quantum dot [the antibody being the particle, or alternatively the quantum dot being the particle] as is well-known in the immunoassay art. Similarly, “a second particle that has a larger average particle diameter than that of the first particle and specifically binds to the target substance” encompasses a second particle as described by Applicant in the specification and any equivalents, including beads or particles well-known in the immunoassay art as a substrate for immobilizing a molecule or complex for isolation or a wash. Moreover, polarization anisotropy, such as disclosed in the prior art below, is recited at a high level of generality and thus encompasses well-known, routine, and conventional polarization anisotropy. Examiner notes that the equation recited in claim 2 is the judicial exception itself, and therefore cannot be considered a limitation that amounts to significantly more than the judicial exception.
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.
Claim(s) 1 is/are rejected under 35 U.S.C. 103 as being unpatentable over
Muramatsu (JP-H0772155-A) (cited in Applicant’s IDS of 12/1/23 and cited in the International Search Report for PCT/JP2022/022413)
in view of Sekar (US 20070054308).
Applicant’s claim 1 recites:
“A method of determining at least any one of the presence or absence, and a concentration, of a target substance in a sample liquid, the method comprising the steps of: (a) preparing a first particle that specifically binds to the target substance and contains a rare earth complex, and a second particle that has a larger average particle diameter than that of the first particle and specifically binds to the target substance; (b) mixing the sample liquid, the first particle, and the second particle to provide a mixed liquid; and (c) determining at least any one of the presence or absence, and the concentration, of the target substance from polarization anisotropy of the mixed liquid obtained in the step (b).”
Regarding Applicant’s claim 1, see the English translation of the abstract of Muramatsu which discloses a measuring method for antigen-antibody reaction to separate a reaction bonded substance from an unreacted substance and to clean them and whose measuring sensitivity can be increased more than that of an ordinary FIA (fluoroimmunoassay). A first reagent which is composed of insoluble magnetic particles which have an antibody or an antigen against an antigen or antibody to be measured is provided in a liquid medium in a reaction container. The insoluble magnetic particles are made to adhere to the wall of the reaction container by the action of a magnetic field, and the liquid medium is removed. A second reagent which is composed of insoluble fluorescent-pigment-labeled particles and which carries an antibody or antigen against an antigen or antibody to be measured is provided in a liquid medium, with the insoluble magnetic particles which have adhered to the wall of the reaction container. The insoluble magnetic particles are made to adhere to the wall of the reaction container by the action of a magnetic field, the liquid medium and the unreacted insoluble fluorescent-pigment labeling particles are removed, and the fluorescent intensity of the insoluble fluorescent-pigment-labeled particles which have reacted with the insoluble magnetic particles is then measured.
See also claim 1 of Muramatsu, which recites the same as above.
However Muramatsu is silent as to the determination of the presence, absence, or concentration of the target substance from polarization anisotropy.
Muramatsu however does disclose that conventionally, immunoassays utilizing an antigen-antibody reaction [can involve a variety of ways to label the antibody or antigen, such as with] a radioisotope (RI), an enzyme, or a fluorescent substance, and such immunoassays can include radioimmunoassays combined with light-emitting substance (RIA), enzyme immunoassay (EIA), fluorescence immunoassay (FIA). Muramatsu’s method improves upon these conventional assays. See pages 2-3 of the English translation provided. Examiner notes that such assays are well-known for detecting the presence, absence, or concentration of an analyte.
Muramatsu is silent as to the determination of the presence, absence, or concentration of the target substance from polarization anisotropy.
However, using polarization anisotropy would have been an obvious alternative to the skilled artisan as it was a known method of detecting a target, as shown by Sekar in disclosing that binding of proteins to aptamers attached to particles was assessed by fluorescence anisotropy. Anti-thrombin aptamer that was labeled and attached to beads. The thrombin aptamer-coupled particles were exposed to thrombin protein, and the change in fluorescence anisotropy was measured. An increase in anisotropy (FIG. 1) was observed upon addition of 100 nM thrombin. Para. 0104.
While Muramatsu is silent as to polarization anisotropy using particles with binding agents for binding and detecting target analyte, such technique is also known in the immunoassay art for detecting the presence or concentration of a target analyte (see Sekar, paras. 0044, 0058, 0063-0064 and 0104). It would have been obvious to one skilled in the art to utilize the particles of Muramatsu in the known technique of polarization anisotropy in a familiar manner as an alternative detection technique. One skilled in the art would have had reasonable expectation of success given that Muramatsu gives examples of detection techniques such as radioimmunoassays combined with light-emitting substance (RIA), enzyme immunoassay (EIA), fluorescence immunoassay (FIA) (page 2-3 of the English translation) and such examples are non-limiting. Moreover, Sekar teaches using that polarization anisotropy can be used to detect analytes where the analytes are immobilized to particles (paras. 0029, 0058, 0092, 0104).
Claim(s) 1 is/are rejected under 35 U.S.C. 103 as being unpatentable over Connolly (CA 3046849)
in view of Muramatsu (JP-H0772155-A) (cited in Applicant’s IDS of 12/1/23 and cited in the International Search Report for PCT/JP2022/022413).
Applicant’s claim 1 recites:
“A method of determining at least any one of the presence or absence, and a concentration, of a target substance in a sample liquid, the method comprising the steps of: (a) preparing a first particle that specifically binds to the target substance and contains a rare earth complex, and a second particle that has a larger average particle diameter than that of the first particle and specifically binds to the target substance; (b) mixing the sample liquid, the first particle, and the second particle to provide a mixed liquid; and (c) determining at least any one of the presence or absence, and the concentration, of the target substance from polarization anisotropy of the mixed liquid obtained in the step (b).”
Regarding Applicant’s claim 1, Connolly discloses the following.
In one embodiment, a bead-based magnetic assay system for detecting a complex including an analyte based on optically detected magnetic resonance (ODMR) includes a plurality of functionalized beads of a first type, which are magnetic functionalized beads and are functionalized to include a first moiety that associates with an analyte under suitable conditions, a plurality of functionalized beads of a second type, which are functionalized to include a second moiety that associates with the analyte…The functionalized beads of the first type can include [magnetic material.] The functionalized beads of the second type can be fluorescent functionalized beads. In other embodiments, the functionalized beads of the second type can be magnetic functionalized beads including a quantity of magnetic material distinguishable from the functionalized beads of the first type….Para. 0008.
As shown in FIG. 2, a method 200 of detecting a complex including an analyte includes contacting 210 a sample in a solution with a population of magnetic functionalized beads of a first type, contacting 220 the sample solution with a population of fluorescent functionalized beads of a second type, illuminating 230 the complex with incident light that excites fluorescence within the functionalized beads of the second type, and detecting 240 the complex including the analyte by analyzing the fluorescence. Para. 0061.
If bead A and B have different size, a similar discrimination approach may be used that ignores this size difference when evaluating the magnitude of candidate signals and applies the same single-parameter quantification strategy to all signals. This may produce signals for bead A, bead B and complexes that are not proportional to their magnetic moments, but are distinct and allow for accurate discrimination. Para. 0096
Discrimination by anisotropy
Magnetic particles may exhibit an anisotropic response to a magnetic field, due to preferential magnetization along certain crystal axes in a single magnetic domain or along certain directions in a multi-domain particle or a composite magnetic bead containing many particles. Rod-shaped nanoparticles, for example, typically can be magnetized more easily along the rod axis. Synthesizing a spherical bead containing oriented magnetic nanorods would produce an anisotropic magnetic susceptibility in the bead. Also para. 0096.
The magnetic anisotropy of a bead can be probed by imaging immobilized beads multiple times, using multiple directions of an applied magnetic field. As shown in FIG. 8C, a metric for magnetic anistotropy can be constructed from the difference in magnetic signals obtained from the different orientations. Imaging at three distinct directions is sufficient to determine the orientation and
degree of anisotropy for a particle even if the particle orientation is not known in advance. If bead A and bead B have zero and nonzero magnetic anisotropy, respectively, then images acquired with the imaging magnetic field rotated in different directions will produce identical signals for bead A, but different signals for bead B. Complex signals will have nonzero anisotropy, but less than that of bead B. Para. 0097.
Magnetic beads of different size, but similar composition, may produce magnetic image signals that are distinguishable by their spatial scale. This may allow for discrimination between bead A, bead B, and complexes, despite bead A and bead B having nominally identical magnetic properties. Para. 0102.
If bead A and bead B have different size, but similar magnetic properties, then spatial scale of magnetic image signals may be used not only to discriminate between the two, but also to identify A-B complexes. Complexes have spatially broad signals that also contain shorter-scale spatial components. Para. 0105.
One method for identifying complexes is to first identify all broad signals (including both bead B and complex signals) and then subtract a characteristic bead B signal (such as the mean of many bead B signals imaged separately) from each. Variations in imaging accuracy and in the uniformity of bead B magnetization will cause this difference to be nonzero for bead B signals, however the difference will generally have broad spatial scale. For the complex signals, however, subtracting the characteristic bead B signal will leave behind the sharper bead A signal. These cases may be distinguished by spatial filtering of the signal differences. Para. 0106.
However, Connolly does not disclose that one of the particles [such as the smaller particle] contains a rare earth complex.
However, Muramatsu discloses a labeling or fluorescent dye can include a rare earth chelate such as samarium (Sm). See Page 4.
Since Muramatsu teaches that a fluorescent dye can be a rare earth chelate such as samarium, it would have been obvious to one skilled in the art to utilize a rare earth chelate such as samarium in the fluorescent particle in Connolly. Examiner notes the Connolly, as discussed above, teaches that the particles of the disclosed system may be different sizes, thus encompassing a system in which the smaller of the two particles has the fluorescent dye.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Ann Montgomery whose telephone number is (571)272-0894. The examiner can normally be reached Mon-Fri, 9-5:30 PM PST.
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/Ann Montgomery/ Primary Examiner, Art Unit 1678
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