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.
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 12/05/2025 has been entered.
Priority
Acknowledgment is made of the present application as a proper National Stage (371) entry of PCT Application No. PCT/US2020/022399, filed 03/12/2020, which claims benefit under 35 U.S.C. 119(e) to provisional application No. 62/817,433, filed 03/12/2019.
Status of the Claims
Claims 22, 23 and 26-33 are pending; claims 1-21, 24, and 25 are canceled; claim 22 is amended; claims 31-33 are newly recited. No claims are withdrawn. Claims 22, 23 and 26-33 are examined.
Withdrawn Objections/Rejections
See as indicated in detail at the Advisory Action (12/04/2025), the previous rejections of claims 28 and 29 under 35 U.S.C. 112(a) are withdrawn in response to Applicant’s remarks.
The previous rejection of claims under 35 U.S.C. 103 is withdrawn following RCE. See new grounds of rejection set forth in detail above, citing prior art uncovered during an updated search and consideration.
Claim Interpretation
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
This application includes one or more claim limitations that do not use the word “means,” but are nonetheless being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, because the claim limitation(s) uses a generic placeholder that is coupled with functional language without reciting sufficient structure to perform the recited function and the generic placeholder is not preceded by a structural modifier.
Such claim limitation(s) is/are: “controller” in claim 22.
Claim 22 recites the generic placeholder “controller” coupled with the functional language the controller is used for “identifying…the presence of the target analyte in the sample based on electromagnetic radiation detected by the detector”.
Because this/these claim limitation(s) is/are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it/they is/are being interpreted to cover the corresponding structure described in the specification as performing the claimed function, and equivalents thereof.
The originally filed specification at page 14, para [0061] indicates that the controller includes non-transitory computer-readable medium with program instructions stored thereon for carrying out the steps conducted by the analyzer, see further describing that controller (140 of Figure 1) includes a processor, a memory and a network interface. See further page 15, the processor of the “controller” is described as including a computer processing element, e.g., a central CPU, and integrated circuit that performs processor operations, a digital signal processor (DSP), or a network processor.
As such, based on applicant’s originally filed specification, the controller is considered to be a computer programmed to carry out the algorithm (a computer programmed to identify the presence of the target analyte based on the detected electromagnetic radiation detected by the detector).
See MPEP 2181, II, B, For a computer-implemented 35 U.S.C. 112(f) claim limitation, the specification must disclose an algorithm for performing the claimed specific computer function, or else the claim is indefinite under 35 U.S.C. 112(b). See Net MoneyIN, Inc. v. Verisign. Inc., 545 F.3d 1359, 1367, 88 USPQ2d 1751, 1757 (Fed. Cir. 2008).
In cases involving a special purpose computer-implemented means-plus-function limitation, the Federal Circuit has consistently required that the structure be more than simply a general purpose computer or microprocessor and that the specification must disclose an algorithm for performing the claimed function. See, e.g., Noah Systems Inc. v. Intuit Inc., 675 F.3d 1302, 1312, 102 USPQ2d 1410, 1417 (Fed. Cir. 2012); Aristocrat, 521 F.3d at 1333, 86 USPQ2d at 1239.
Para [0155] describes that fluorescent particles emit photons that are registered by the detector (122), the photon intensity recorded by the detector, sampling time divided into bins, wherein the bins are uniform and arbitrary time segments with freely selectable time channel widths. The number of signals contained in each bins is evaluated, that statistical analytical methods are used to determine when a label or particle is present vs. a detected artifact, artifacts discarded while single bins or sections of binds containing label are counted.
In light of the level of ordinary skill in the art, Applicant’s description in the specification is sufficient structure (algorithm) for describing how to program a computer to perform the claimed functions.
If applicant does not intend to have this/these limitation(s) interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitation(s) to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph (e.g., by reciting sufficient structure to perform the claimed function); or (2) present a sufficient showing that the claim limitation(s) recite(s) sufficient structure to perform the claimed function so as to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph.
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.
Claim 23 is 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 23 is indefinite because the claim recites “further comprising moving the paramagnetic beads through the introduced wash buffer using the magnet”, however, independent claim 22 from which 23 depends already recites “operating a pump to pump the wash buffer through a portion of the cartridge and over the paramagnetic beads while the paramagnetic beads are held in place so as to wash the unbound fluorescent label away from the paramagnetic capture beads”. The claim language is indefinite because “moving” the beads contradicts the limitation that already specifies that the beads are held in place, see the language of claim 22 suggest the wash buffer is already (prior to claim 23) pumped through (to wash away).
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) 22-23, 26-27 and 32-33 are rejected under 35 U.S.C. 103 as being obvious over Ho, US PG Pub No. 2005/0221281 in view of Kato et al., JPH10221343A (machine obtained English translation obtained via Google Patents, cited previously).
Ho et al. teach method of detecting the presence of a target analyte in a sample (abstract, further see para [0074], detecting an signal corresponds to analyte concentration), the method comprising receiving a cartridge (referred to by Ho as a biochip) in an analyzer system such that the cartridge is coupled to a motor of the analyzer system (see para [0061]), rotating the cartridge using the motor so as to move at least a portion of the sample to a mixing chamber in the cartridge (see para [0052], Ho describe sample can be added to sample port 15 (center), and distributed to reaction wells (which reads on mixing chamber) 13 by centrifugal force, i.e., rotating the cartridge), mixing the portion of the sample in the mixing chamber by further rotating the cartridge (para [0063], rotational stage creates turbulence and mixing at the reaction well) so as to bind the target analyte and a fluorescent label to paramagnetic capture beads (see for example, paras [0067], magnetic beads are super-paramagnetic, and further [0077] and Figure 9, Ho describe causing binding between target and magnetic capture beads in the reaction well, i.e. mixing chamber, and with labeled reagent, see further para [0076] can be used for a variety of bioassays, including fluorescence, i.e., fluorescent label), introducing wash buffer into the cartridge (see paras [0067], and further [0071]), operating a pump to pump pumping the wash buffer through a portion of the cartridge and over the paramagnetic capture beads while the paramagnetic capture beads are held in place so as to wash unbound fluorescent label away from the paramagnetic capture beads (para [0067] Ho describe magnetic beads are held in place while residual solutions are washed away, see also para [0071], referring to wash buffer, Ho teach a variety of pumping mechanisms used to suck liquid out of reaction well).
See further, Ho at paras [0116] and [0143] describe embodiments comprising introducing elution buffer into the cartridge so as to elute captured target from the paramagnetic capture beads for subsequent downstream applications.
Ho further teach their methods comprising directing electromagnetic radiation from an electromagnetic radiation source (see light source located above or below biochip) to form an interrogation space within the cartridge (see e.g., para [0152]), receiving, in a detector, electromagnetic radiation emitted in the interrogation space by the fluorescent label if the fluorescent label is present in the interrogation space (paras [0146]-[0147], [0153] detector receiving the signal); and see Ho, at the abstract and paras [00033], [0034],[0074]) teach a processor configured to process optical properties/detection (computer programmed to determine presence of analyte based on signal obtained at the detector), addressing identifying, using a controller to detect the presence of the target analyte (see further Ho, describing a computer programmed to measure the optical properties received from the detector, see further para [0073]) in the sample based on electromagnetic radiation detected by the detector (see further, Ho’s systems/methods apply to a variety of analytes, including proteins, nucleic acids, cells, receptors, and the like).
Although embodiments of Ho comprise both eluting and also detection of a detectable label (such as a fluorescent dye) Ho fails to clearly recite performing elution followed by detection of the eluted label.
Kato et al. teach methods of measuring target (protein) which enables high accuracy without non-specific binding (see abstract), Kato et al.’s method comprising eluting the labeled reagent, detecting the amount of eluted label (eluting with an eluent containing antigen peptide, i.e., and elution buffer (para [0015], same buffer as mobile phase, phosphate buffer), see also claim 1, para [0005], see further paras [0009], [0014], [0018] non-specifically bound labeled reagent is not eluted).
It would have been prima facie obvious to one having ordinary skill in the art to have modified the methods described in Ho such to use their analysis system to first elute label (such as fluorescent label) and then subsequently detect the eluted label (as in Kato) as an obvious matter of applying a known technique to a known method, specifically one motivated to do so to improve detection accuracy (reduce non-specific binding). In particular, the prior art taught the base method/concept, of performing an on cartridge/disc assay, comprising a series of steps performed within a reaction chamber including binding, washing, elution and detection (see Ho), Ho specifically disclose reagents can be provided and released from reagent cavities on the cartridge/disc component. Ho does teach performing actions including elution and detection. Further it was known in the art that methods comprising a step of eluting prior to detection of eluted label enable high accuracy without non-specific binding, as such one would be motivated to first elute labels and then detection in order to improve detection with respect to nonspecific binding.
One having ordinary skill in the art would have a reasonable expectation of success because the disclosure of Ho’s system and methods does not appear limited to any particular order, as a result, one would expect success providing elution buffer in a sequence that would allow for elution prior to detection.
Regarding claim 23, although the limitations of claim 23 are addressed under 35 U.S.C. 112(b) above, see further Ho is describing a pumping step comprising introducing wash solution to the reaction chamber (which reads on the claimed mixed chamber), followed by an action of removing the magnet off before moving the magnet back on to capture/immobilize the paramagnetic particles, and pump the wash solution from the chamber (see for example, para [0130], and also described at para [0067] (collection with magnet, and resuspension, achieved by moving the magnet in and out).
Regarding claim 26, see as discussed in detail previously above, Ho addresses holding by magnetic force, the capture beads during the wash step (while washing away unbound label, such as fluorescent label, see as cited above Ho teach assays including fluorescent dye label).
Regarding claim 27, see as cited above Ho is teaching holding the magnetic beads in the reaction chamber (i.e., mixing chamber as presently claimed) during the pumping step to pump wash buffer over the capture beads.
Regarding claims 32 and 33, Ho teach a method substantially as claimed, which involves further steps of elution (eluting from capture beads), however, Ho is silent as to the details of the elution and as such fails to teach using a magnet to enable relative motion between buffer and beads to elute and disperse as claimed (claim 32), and fails to teach the interrogation space is formed in the elution buffer (claim 33).
However, regarding new claim 32, Ho as discussed previously above, describes a combination of centrifugal and magnetic forces applied, see for example at para [0067], Ho et al. teach taking action of applying a magnetic field to immobilize captured target, and moving the magnet out to achieve simple resuspension.
Although Ho does not specifically recite using a magnet to enable motion between the elution buffer and the capture beads to elute and disperse the fluorescent label away from the capture beads, using the magnet to immobilize the eluted magnetic beads (i.e., resulting in interrogation space (detection) of the eluted label in the elution buffer, it would have been further obvious that during the elution step of Ho (when subjected to the eluent) that the magnet be moved in and out, to facilitate elution, prior to back in to subsequently immobilize (thereby removing) the magnetic capture beads away for detection, namely because Ho specifically disclose achieving mixing actions using this magnetic technique (mixing generally). One having ordinary skill in the art would have a reasonable expectation of success given that it would be expected that an action of mixing would be applied upon introducing the elution buffer to the captured component in order to appropriately bring the elution buffer and beads into contact, such to ensure all captured beads are eluted, and considering Ho already describe elution as part of their described methods.
Claim(s) 28 and 29 are rejected under 35 U.S.C. 103 as being unpatentable over Ho in view of Kato, as applied to claim 22 above, and further in view of Phan et al., WO 2005/001429A2.
Regarding claims 28 and 29, Ho describes a method using an analyzer and a cartridge substantially as claimed, however Ho teach their reagents (e.g., buffers, etc.) pre-loaded onto the chip device (para [0021], for ease, see as cited above preloaded at reagent cavities).
As such, Ho fails to teach their method wherein the wash buffer (claim 28) and elution buffer (claim 29) are introduced into the cartridge after the cartridge is received into the analyzer.
Phan et al. is another example of an apparatus that employs a cartridge/biochip or bio-disc, for performing an assay. Phan describe, buffers, liquid reagents, or reagents dissolved in buffer can be pre-loaded into reservoirs int the disc, see for example, in reference to Figure 22, Phan refer to introducing reagent to a desired chamber/reservoir by way of an inlet port (also Figure 23, shown as inlet ports 224 and 226) (see for example, page 3, second paragraph). See also, Phan describe, that in use, solvent or buffers can be added/loaded into a desired chamber by way of the inlet port (see for example page 16, end of paragraph 2; page 18, end of paragraph 2).
See further MPEP 2144.04 at C. regarding changes in sequence of adding ingredients, generally, selection of any order of performing process steps is prima facie obvious in the absence of new or unexpected results.
In the present case, it was known in the art that regarding these types of assays, using biochips/discs for performing assay in an analyzer, it was known to provide liquid reagents either preloaded (as in Ho), or that reagents such as buffers/solutions, can can be loaded to the chips/discs/cartridges by way of inlets formed in the top of the chamber/reservoirs intended for these reagents (Phan et al.), see for example, Phan teach an inlet port above a given chamber (cited above).
Absent evidence of unexpected results or criticality, it would have been obvious to have modified the disc of Ho such to provide inlet ports for introducing buffer/reagents (e.g., wash buffer and elution buffer to reaction chambers) as an obvious matter of one art recognized way of loading reagent for another, considering both were known in the art for introducing reagents/solutions/buffers to these types of assays (assaying using biochips/discs/cartridges). Even further, absent evidence of unexpected results or critically, it would have been further obvious to have introduced either before or after the disc/cartridge is introduced into the analyzer, as it appears that the time at which the wash buffer and elution buffers are added (whether preloaded before placed into the analyzer, or loaded once placed in the analyzer, but before assay) is obvious matter of selection of any order to step prior to initiation of the assay. It does not appear that when the reagent is loaded would change the outcome of the meth with regard the assay/detection.
Claim(s) 30 and 31 are rejected under 35 U.S.C. 103 as being unpatentable over Ho in view of Kato, as applied to claim 22 above, and further in view of Hitko et al., US PG Pub No. 2014/0322794A1.
Regarding claims 30 and 31, Kato is describing elution comprising elution of the label (eluting with eluent containing antigen), and further see Ho is describing elution from paramagnetic beads (eluting the paramagnetic particle from the targeted analyte, claim 31), both references describe performing an elution.
However, the cited prior art fails to teach eluting comprising an eluent that cleaves the bond (between the label and antigen, or between the paramagnetic particle and the analyte).
However, regarding elution of a bound target analyte, the art recognized multiple suitable methods for accomplishing elution, see for example Hitko et al. teach each of competing off a target (the technique as described in Kato), cleaving a cleavable linker, using a buffer to perturb (non-specific elution).
It would have been further prima facie obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have modified the methods as taught by Ho and Kato, to further modify the binding assay to utilize a cleavable linker, eluting with an elution buffer that cleaves the cleavable linker, rather than displacement as in Kato for example, as an obvious matter of a simple substitution of one art recognized manner of achieving elution of a targeted analyte for another, one having a reasonable expectation of success because suitable elution techniques were known and available to one having ordinary skill, Hitko teaching the finite list of three suitable alternatives, cleavable linker recognized as achieving the same result as would competitive displacement (as in Kato). One having ordinary skill in the art would have found it obvious to have arrived at an elution buffer that cleaves by pursing the finite list of suitable alternatives, recognized in the art for eluting a targeted analyte.
Even further, considering the prior art and that it was known to elute either of the label (Kato) or the capture bead (Ho), it would have been prima facie obvious as a simple substitution of one technique for the other, both resulting in elution of label for subsequent detection, both resulting in separation of the capture particle, and as such resulting in an expectation of reduced non-specific binding (since capture particle is removed from the complex either way). One having ordinary skill would have a reasonable expectation eluting, and thereby cleaving the bond between the capture bead or between the label and the analyte, as both were recognized targets for elution known in the art regarding separation of labeled complex (as supported by each of Kato and Ho).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Copending 18/597,424
Claims 22-23, 26-29 and 32-33 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of copending Application No. 18/597,424 in view of Ho and Kato et al. (each cited previously above).
Although the claims at issue are not identical, they are not patentably distinct from each other because:
Copending ’424 similarly recites a method of detecting the presence of a target analyte in a sample (see for example claim 9, and the analyzer for the method claims 1 and 9), the method comprising (‘424 at claim 9 for example) receiving a cartridge in an analyzer system such that the cartridge is coupled to a motor of the analyzer system, rotating the cartridge using the motor to move a volume of the sample toward a mixing chamber in the cartridge, mixing the volume by moving the cartridge to bind the target analyte, a label (fluorescent label, see for examples claims 10 and 11 of ‘424), and paramagnetic capture beads. Copending ‘424 further recites a method comprising introducing a wash buffer to the cartridge and an elution buffer (see ‘424 at claim 9). See also ‘434 at claim 10 reciting the steps of directing electromagnetic radiation to form an interrogation space, receiving radiation emitted at the detector, identifying using a controller, presence of target based on the detected electromagnetic radiation detected by the detector.
Although copending ‘424 does recite their analyzer comprising a pump (see for example claims 2 and 3 describing the analyzer), and does recite pushing the fluids (including washing fluid) along an isolated path (through a portion of the cartridge) to the mixing chamber (where the bound complex is located), ‘424 differs from that which is presently claimed in that it recites using the magnet to move the capture beads out of the mixing chamber, and as such fails to recite/is silent as to the claimed action of the instant method operating the pump to pump the washing buffer through a portion of the cartridge over the paramagnetic capture beads while the capture beads are held in place, followed by introducing the elution buffer to elute the fluorescent label prior to the detecting steps (claim 22).
See as cited in detail previously above, Ho teach an analyzer and describe using said analyzer (method) substantially similar to that presently claimed (see full citations in detail above). Particularly at para [0067] Ho describe magnetic beads are held in place while residual solutions are washed away, see also para [0071], referring to wash buffer, Ho teach a variety of pumping mechanisms used to suck liquid out of reaction well).
Although embodiments of Ho comprise both eluting and also detection of a detectable label, such as a fluorescent dye, Ho fails to clearly recite performing elution followed by detection of the eluted label.
Kato et al. teach methods of measuring target (protein) which enables high accuracy without non-specific binding (see abstract), Kato et al.’s method comprising eluting the labeled reagent, detecting the amount of eluted label (eluting with an eluent containing antigen peptide, i.e., and elution buffer (para [0015], same buffer as mobile phase, phosphate buffer), see also claim 1, para [0005], see further paras [0009], [0014], [0018] non-specifically bound labeled reagent is not eluted).
It would have been prima facie obvious to one having ordinary skill before the effective filing date of the claimed invention to have modified copending ‘424 in order to apply the pump to remove the wash fluid, as in Ho, namely by holding the magnetic particle in place with the magnet (addressing claims 22 and 26), as in Kato, one motivated to do so as an obvious matter of a simple substitution of one art recognized and known technique for washing away unbound reagent for another. In particular, the copending application and Ho teach to art recognized ways to wash unbound components from bound complex on an analyzer cartridge (the copending referring to using the magnet to move the capture complex from the wash solution, Ho teaching using the pump to pump unbound components away while the magnet holds the capture complex in place). Both achieve the same predictable result, namely separating bound from unbound reagent. Further one would have a reasonable expectation of success because ‘424 describes sufficient structure for achieving this modification, the analyzer of ‘424 similarly described as having a pump and a magnet to control the paramagnetic particles, so the system would be capable of pumping out the fluid and holding the capture particles in place, and one would expect success because the modification achieves the same result remove of unbound component.
Regarding claim 23, although the limitations of claim 23 are addressed under 35 U.S.C. 112(b) above, see further Ho is describing a pumping step comprising introducing wash solution to the reaction chamber (which reads on the claimed mixed chamber), followed by an action of removing the magnet off before moving the magnet back on to capture/immobilize the paramagnetic particles, and pump the wash solution from the chamber (see for example, para [0130], and also described at para [0067] (collection with magnet, and resuspension, achieved by moving the magnet in and out).
It would have been prima facie obvious to have further moved the magnet in and out (thereby mixing the beads in the washing fluid, i.e., moving through the wash fluid before pumping out) as an obvious matter of applying a known technique known for washing (known to move magnet on and off to cause mixing to remove unbound reagent from the complex) as in Ho. One having ordinary skill in the art would have a reasonable expectation of success modifying the method of ‘424 in this way given that similarly to ‘424, Ho is also referring to washing complex comprising magnetic capture beads, and considering ‘424 (as discussed above) describes an analyzer and cartridge with structure that would accommodate such modification (magnet that can be manipulated to control the capture bead motion).
Regarding claim 27, see as cited above, the combination of ‘424 and the cited art addresses pumping wash buffer through the mixing chamber while the beads are held by the magnet.
Regarding claims 28 and 29, see ‘424 at claim 9, the method comprises first receiving cartridge, and subsequent steps following the receiving the cartridge in the analyzer, such as introducing series of fluids including wash and elution buffer.
Regarding new claim 32, ‘424 fails to recite using a magnet to enable motion between the elution buffer and capture beads to elute and disperse the label away from the capture beads. However, Ho as discussed previously above, describes a combination of centrifugal and magnetic forces applied, see for example at para [0067], Ho et al. teach taking action of applying a magnetic field to immobilize captured target, and moving the magnet out to achieve simple resuspension. Also as cited above, each of ‘424 and Ho refer to an elution step (see further Ho cited in detail previously above).
Although Ho does not specifically recite using a magnet to enable motion between the elution buffer and the capture beads to elute and disperse the fluorescent label away from the capture beads, using the magnet to immobilize the eluted magnetic beads (i.e., resulting in interrogation space (detection) of the eluted label in the elution buffer (thereby also addressing claim 33), it would have been further prima facie obvious that during the elution that the magnet be moved in and out, to facilitate elution, prior to back in to subsequently immobilize (thereby removing) the magnetic capture beads away for detection, namely because Ho specifically disclose achieving mixing actions using this magnetic technique. One having ordinary skill in the art would have a reasonable expectation of success given that it would be expected that an action of mixing would be applied upon introducing the elution buffer to the captured component in order to appropriately bring the elution buffer and beads into contact, such to ensure all captured beads are eluted, and considering Ho already describe elution as part of their described methods.
Claims 30 and 31 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of copending Application No. 18/597,424 in view of Ho and Kato et al., as applied to claim 22, and further in view of Hitko et al., US PG Pub No. 2014/0322794A1.
Regarding claims 30 and 31, ‘424 recite elution buffer, and the copending in view of Ho and Kato is describing elution comprising elution of the label (eluting with eluent containing antigen), and further see Ho is describing elution from paramagnetic beads (eluting the paramagnetic particle from the targeted analyte, claim 31), both references describe performing an elution.
However, the cited prior art fails to teach eluting comprising an eluent that cleaves the bond (between the label and antigen, or between the paramagnetic particle and the analyte).
However, regarding elution of a bound target analyte, the art recognized multiple suitable methods for accomplishing elution, see for example Hitko et al. teach each of competing off a target (the technique as described in Kato), cleaving a cleavable linker, using a buffer to perturb (non-specific elution).
It would have been further prima facie obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have modified the methods as taught by ‘424 in view of Ho and Kato, to further modify the binding assay to elute capture analyte in order to reduce non-specific binding (thereby improving detection), and specifically to have utilized a cleavable linker, eluting with an elution buffer that cleaves the cleavable linker, rather than displacement as in Kato for example, as an obvious matter of a simple substitution of one art recognized manner of achieving elution of a targeted analyte for another, one having a reasonable expectation of success because suitable elution techniques were known and available to one having ordinary skill, Hitko teaching the finite list of 3 suitable alternatives, cleavable linker recognized as achieving the same result as would competitive displacement (as in Kato). Further, as noted ‘424 does recite elution, however, fails to recite details specific to the elution (recites sending through an elution buffer).
Even further, considering the prior art and that it was known to elute either of the label (Kato) or the capture bead (Ho), it would have been prima facie obvious as a simple substitution of one technique for the other (using a cleavable linker instead of competitive displacement), both resulting in elution of label for subsequent detection, both resulting in separation of the capture particle, and as such resulting in an expectation of reduced non-specific binding (since capture particle is removed from the complex either way). One having ordinary skill would have a reasonable expectation eluting, and thereby cleaving the bond between the capture bead or between the label and the analyte, as both were recognized targets for elution known in the art regarding separation of labeled complex (as supported by each of Kato and Ho).
Response to Arguments
Applicant's arguments filed 11/24/2025 have been fully considered but they are not persuasive for the following reasons:
Referring to remarks page 6, specific to the rejection of claims 28 and 29 under 35 U.S.C. 112(a), see as indicated previously (Advisory action, 12/04/2025), the rejection is withdrawn in response to remarks.
Regarding the previous rejection of claims under 35 U.S.C. 103, citing Poc Medical systems in view of Strohmeier et al., Kato and Horii, at remarks page 7 Applicant refers to amendments to the claims (claims are amended in order to recite “operating a pump to pump the wash buffer through a portion of the cartridge and over the paramagnetic capture beads while the paramagnetic capture beads are held in place so as to wash unbound fluorescent label away from the paramagnetic capture beads”). However, upon further search/consideration following RCE, new grounds of rejection set forth in detail below.
Regarding remarks at page 8, regarding claim 30, Applicant argues Kato is teaching a different form of elution, namely fails to teach an elution buffer that cleaves a cleavable linker. In response, Applicant’s arguments are considered, see the amended grounds of rejection set forth in detail above.
Applicant remarks on the rejection of claims on the ground of non-statutory double patenting (remarks pages 8-9), indicating that the application is the earlier filed application in the rejection and that all other rejections are addressed . However, the application is not considered otherwise to be condition for allowance at the present time (see rejections above, under 35 U.S.C. 112(b) and 35 U.S.C. 103), and as such the non-statutory double patenting rejection is as set forth in detail above.
Correspondence
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/ELLEN J MARCSISIN/ Primary Examiner, Art Unit 1677