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 .
Response to Arguments
Applicant's arguments filed 7/21/2026 have been fully considered but they are not persuasive.
Specifically, applicant argues that "drug candidates" are candidate compounds deliberately included in the assay mixture for affinity-selection screening and that Hudson et al does not disclose drug candidates or an assay mixture within an assay vessel, the assay mixture comprising a plurality of drug candidates and at least one binding target immobilized onto a plurality of magnetic particles.
However, in response to the above argument, Hudson et al teaches an assay mixture within an assay vessel (i.e. a reaction vessel), the assay mixture comprising a plurality of drug candidates (wherein the sample includes analytes (which are drug candidates) and at least one binding target (i.e. antibody) immobilized onto a plurality of magnetic particles (which is a magnetic bead) (see [0043], [0085] and [0087]).
Furthermore, applicant argues that the Office Action's interpretation, which treats a diagnostic analyte in Hudson as both a "drug candidate" and a "hit compound," is broader than the broadest reasonable interpretation in light of the specification. Properly construed, claim 1 requires an affinity-selection workflow in which a plurality of candidate compounds is intentionally brought into contact with a separate immobilized binding target, and the method identifies which members of that plurality bind to the target.
However, it is noted that in response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e. that an affinity -selection workflow is required and that the drug candidate and the hit compound are separate compounds) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
In addition, applicant argues that Hudson et al do not teach forming an assay mixture containing a plurality of drug candidates and an immobilized binding target to discover which candidates bind.
In response to this argument, examiner Wecker respectfully disagrees as Hudson et al does disclose an assay mixture (i.e. a sample mixture, formed in a reaction vessel) containing a plurality of drug candidates (i.e. a specific analyte, such as a drug compound) and an immobilized binding target (i.e. an antibody on the magnetic particle) (see [0009], [0043], [0053], [0100] and [0163]).
In addition, applicant notes that In Hudson, beads and capture reagents are used because the analyte or analyte panel is predefined. In the present claims, magnetic particles bearing a binding target are used to determine which compounds in a plurality of drug candidates bind to that target.
However, giving the claims their broadest reasonable interpretation, all that is required by the claims is that there is an anayte, not whether the analyte is unknown or predefined. For instance, Hudson et al teaches “assaying large panels of analytes, such as tumor markers, mass spectrometry is first used as a screening assay to identify a subset of markers that are positive for the sample, and the chemistry/immune analyzer is then used to confirm that these markers are positive” (thereby identifying the markers is being found in the sample) (see [0207]). Furthermore, Hudson et al teaches that the mass spectrometry test 324 may identify one or more analytes in the panel of analytes (e.g., of a number of potential drugs of abuse, a number of proteins that form a panel or a number of steroids that form a panel) in the sample (which is being interpreted as the assay mixture) and thereby determining the particular amounts (i.e. levels or concentrations) of the one or more analytes in the sample (see [0087] of Hudson et al).
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1, 4-7, 9 and 15-17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hudson et al (US PGPub 2021/0003586).
Regarding Claim 1, Hudson et al teaches a method for identifying a set of hit compounds (i.e. target compounds, such as drug compounds) having a selected affinity (i.e. selectivity) to a binding target (i.e. an antibody on the magnetic particle/bead) (see [0035] and [0087]), the method comprising:
forming an assay mixture (i.e. a sample mixture) within an assay vessel (referred to as a reaction vessel, wherein an array of holes 504 receives reaction vessels) (see [0080], [0096], [0100], [0139] and [0163]), the assay mixture (the sample mixture, found in the reaction vessel) comprising a plurality of drug candidates (see [0042]-[0043] and [0205]) and at least one binding target (i.e. antibody) immobilized onto a plurality of magnetic particles (see [0053], [0056], [0163], [0213] and [0217]) ; preparing at least a portion of the assay mixture for mass analysis (i.e. mass spectrometry) (see [0052], [0071], [0214] and [0219]); and transferring a sample of the assay mixture containing the set of hit compounds to an open port sampling interface of a mass spectrometer (see [0049]-[0050] and [0072]).
Regarding Claim 4, Hudson et al teaches that transferring the sample is conducted partially or completely prior to preparing the assay mixture for mass analysis (i.e. through ionization) (see [0072]).
Regarding Claim 5, Hudson et al teaches that the sample containing the set of hit compounds comprises bound compound - magnetic particle (i.e. antibody-magnetic particle) components within the assay mixture (see [0053], [0100], [0167]-[0168] and [0213]).
Regarding Claim 6, Hudson et al teaches trapping the magnetic particles within a carrier flow of the mass spectrometer by selectively activating a magnetic force, and subsequently releasing the magnetic particles to a waste flow (i.e. downstream waste station 718 ) by selectively deactivating the magnetic force (see [0075] and [0154]-[0156]).
Regarding Claim 7, Hudson et al teaches trapping the magnetic particle within the open port sampling interface (see [0050] and [0072]).
Regarding Claim 9, Hudson et al teaches transferring a sample containing the set of hit compounds comprises transferring a sample of the assay mixture directly from the assay vessel to the open port sampling interface (see [0074] and claim 86).
Regarding Claim 15, Hudson et al teaches analyzing the set of hit compounds by mass spectrometry, without liquid chromatography (see [0055]).
Regarding Claim 16, Hudson et al teaches forming an assay mixture comprises introducing magnetic particles into the assay vessel (see [0100] and [0213]) , each magnetic particle including at least one binding site for binding to at least one target compound (see [0213] and [0217]).
Regarding Claim 17, Hudson et al teaches generating sample information for the assay mixture, wherein the sample information includes an identifier indicative of each of the one or more compounds, reagents, or other information related to analysis of the sample well (see [0114] and [0207]).
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 2 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Hudson et al as applied to claim 1 above, and further in view of Steyaert et al WO 2021/123360).
Regarding Claim 2, Hudson et al teaches introducing the plurality of drug candidates into the assay vessel by serially adding individual compounds (through a sample introduction apparatus); introducing the magnetic particles into the assay vessel; and incubating the plurality of drug candidates and the magnetic particles under assay conditions (see [0008], [0063], [0100] and [0126]).
Hudson et al does not explicitly disclose that the compounds are introduced from a compound library.
However, in the analogous art affinity purification, Steyaert et al teaches an affinity purification system where compounds used may be introduced through a compound library (see page 43). It would have been obvious to one of ordinary skill in the art to modify the system and method of Hudson et al by utilizing a compound library for the test compounds (as taught by Steyaert et al) for the benefit of enabling the system to be used for high-throughput screening.
Regarding Claim 21, Hudson et al teaches a screening system (see [0090] and [0207]), the system comprising:
a assay vessel preparation module (such as sample preparation processing module 210) configured to introduce a plurality of compounds into an assay vessel (see [0070]-[0071]);
an assay module configured to conduct a binding assay comprising introducing magnetic particles into the assay vessel, each magnetic particle including at least one binding site for binding to at least one target compound (wherein “an aliquoting station comprising at least one pipettor in the analyzer can obtain two or more or more sample aliquots of a sample and can dispense them into two or more reaction vessels. The at least one pipettor in the aliquoting station may provide (e.g., dispense) a first sample aliquot of the sample to a first reaction vessel. One of the sample aliquots may be subjected to an immunoassay test (an example of a primary analysis) in the immunoanalyzer at step 304. The first reaction vessel including the first sample aliquot may be processed by the immunoanalyzer to form a first processed sample aliquot”)(see [0080] and [0100]).; and
an analysis module (referred to as DMS process module 238) configured to serially transfer a sample from the assay vessel into an open port sampling interface of a mass spectrometer and conduct a mass analysis of the transferred sample (see [0072]-[0073]).
Hudson et al does not explicitly disclose that the compounds are introduced from a compound library.
However, in the analogous art affinity purification, Steyaert et al teaches an affinity purification system where compounds used may be introduced through a compound library (see page 43). It would have been obvious to one of ordinary skill in the art to modify the system and method of Hudson et al by utilizing a compound library for the test compounds (as taught by Steyaert et al) for the benefit of enabling the system to be used for high-throughput screening.
Claim(s) 3, 10 and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Hudson et al as applied to claim 1 above, and further in view of Haselton et al (US PGPub 2017/0030903).
Regarding Claim 3, Hudson et al teaches that preparing at least a portion of the assay mixture comprises: separating one or more components of the assay mixture from the set of hit (i.e. target) compounds (see [0058]-[0059] and [0108]).
Hudson et al does not teach that preparing the assay mixture further comprises disrupting a binding interaction between the set of hit compounds and the binding target.
However, in the analogous art of systems and methods are described for isolation, separation and detection of a molecular species, Haselton et al teaches that an interaction between the biomarker capture agent on the bead surface and the biomarker of interest is disrupted using a biomarker release agent (see [0041]). It would have been obvious to one of ordinary skill in the art to modify the system and method of Hudson et al to incorporate a release agent with the assay mixture for the benefit of disrupting the bead complex to release the biomarker (i.e. the analyte of interest) for future analysis.
Regarding Claim 10, Hudson et al teaches inserting a magnet into the assay mixture to retain the magnetic particles adjacent to the magnet; removing the magnet and retained magnetic particle from the assay mixture (see [0140] and [0213]) ; washing the magnetic particles retained adjacent to the magnet with a wash solution (see [0126] and [0213]); and separating hit compounds from the binding target and forming the sample containing a set of hit compounds to be transferred to the open port sampling interface (see [0058]-[0059] and [0108]).
Hudson et al does not teach contacting the magnetic particle with a release agent while the magnetic particles are retained adjacent to the magnet.
However, in the analogous art of systems and methods are described for isolation, separation and detection of a molecular species, Haselton et al teaches that an interaction between the biomarker capture agent on the bead surface and the biomarker of interest is disrupted using a biomarker release agent (see [0041]). It would have been obvious to one of ordinary skill in the art to modify the system and method of Hudson et al to incorporate a release agent with the assay mixture for the benefit of disrupting the bead complex to release the biomarker (i.e. the analyte of interest) for future analysis.
Regarding Claim 13, Hudson et al teaches applying a magnetic force (such as through magnet 508) adjacent the assay vessel to retain the magnetic particles within the assay vessel {see [0140]); aspirating at least a portion of the assay mixture from the assay vessel (through a main sample pipetting station 402) (see [0093], [0123], [0126] and [0140]); washing the magnetic particles within the assay vessel (see [0056] and [0126]); and adding a separation agent to the assay vessel to separate hit compounds from the binding target (see [0058], [0100], [0103] and [0108]).
In addition, Haselton et al also discloses the use of a release agent to separate hit compounds (see [0041]).
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Hudson et al as applied to claim 1 above, and further in view of Amirav (US PGPub 2009/0101814).
Regarding Claim 8, Hudson et al does not disclose that magnetic particle is discarded via exhaust from a sample vaporization chamber of the mass spectrometer.
However, in the analogous art of mass spectrometry systems, Amirav teaches a capillary separated vaporization chamber and nozzle method and device for improved electron ionization liquid chromatography mass spectrometry of samples in a supersonic molecular beam. The device includes a vaporization chamber located upstream of a supersonic nozzle; a capillary separating the vaporization chamber and the supersonic nozzle, means for spray formation from sample in a flowing liquid; a vacuum system into which the supersonic nozzle induces supersonic expansion of the vaporized sample compounds and solvent vapor, for forming a supersonic molecular beam with vibrationally cold sample molecules and vaporized solvent; flythrough electron ionization ion source; mass analyzer; an ion detector and means for data processing of the resulting mass spectral information, for identifying and/or quantifying the chemical content of the sample (see abstract). It would have been obvious to one of ordinary skill in the art to modify the system/method of Hudson et al by incorporating a sample vaporization chamber in the mass spectrometer for the benefit of enabling the magnetic particle to be ejected via vaporization/vacuum of the sample vaporization chamber.
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Hudson et al and Haselton et al as applied to claim 3 above, and further in view of Covey et al (WO 2021/234640), as cited on the IDS.
The applied reference has a common assignee and inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
Regarding Claim 11, the combination of Hudson et al and Haselton et al does not explicitly teach that disrupting the binding interaction comprises introducing an unbinding solvent to the assay mixture to separate the set of hit compounds from the binding target.
However, in the analogous art of affinity selection by mass spectrometry, Covey et al teaches separating the one or more compounds from the probe may include inserting the probe and bound one or more compounds into an unbinding solvent in a separation vessel to unbind the one or more compounds from the probe, and injecting the unbinding solvent and unbound one or more compounds into the flowing solvent at the open end of the open port sampling interface (see [0017]-[0018]). It would have been obvious to one of ordinary skill in the art to utilize an unbinding solvent (as taught by Covey et al) as the separation agent for the benefit of effectively unbinding compounds from the assay mixture for future analysis.
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Hudson et al as applied to claim 1 above, and further in view of Miller (US 10126296).
Regarding Claim 12, Hudson et al teaches the use of magnets 508, wherein these magnets may be used to bind magnetic particles so that any supernatant that is suitable for a downstream mass spectrometric analysis can be performed (see [0140]).
However, Hudson et al does not teach applying an oscillating magnetic force to the magnetic particle to agitate the assay mixture; applying a constant magnetic force to the magnetic particles to retain magnetic particles at a position within the assay mixture; or both.
However, in the analogous art of immunoassay methods and devices, Miller teaches the use of oscillating magnetic fields, as well as static magnetic fields in their immunoassays (see Col. 23, lines 20-56). It would have been obvious to one of ordinary skill in the art to utilize an oscillating magnetic field for the benefit to enabling the magnetic particles to be effectively mixed.
Claims 24 and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Hudson et al as applied to claim 1 above, and further in view of DeWitte et al (US 10088460),
Regarding Claims 24 and 26, Hudson et al does not teach providing sample information associated with the assay vessel indicative of the plurality of compounds introduced into the assay vessel (i.e. an identifier), wherein the analysis module correlates the sample information with the mass analysis generated from the assay vessel to identify any hit compounds that bound to the magnetic particles.
However, in the analogous art of automated systems for sample preparation and analysis, DeWitte et al teaches an information acquisition device 54 which, for example, may be a bar code reader or an RFID receiver. The information acquisition device 54, in turn, may receive information associated with a reagent of the particular reagent container 52 or information associated with the particular reagent container 52 itself. A bar code or RFID antenna is imprinted or positioned on a reagent container 52. The bar code or RFID antenna may be configured to provide information associated with the particular reagent or it may contain an identification (such as an identifier) that is cross-referenced with a Look-Up Table (“LUT”) (not shown) accessible by the sample preparation controller 22 (FIG. 2) (e.g., on the sample preparation controller 22 or on the LIS 28 and accessible by the sample preparation controller 22) and having detailed information regarding the reagent contained therein. The information obtained may be used to identify and/or monitor a respective reagent container 52 and/or the reagent therein. For example, the information may be used to identify the reagent within the reagent container 52, identify the location of the reagent container 52 within the reagent station 46, identify and/or monitor the quantity of reagent remaining in the reagent container 52, and/or identify the expiration date of the reagent within the reagent container 52. Though not specifically shown, the information acquisition device 54 may be mounted onto a track system (not shown) that spans between the specimen dock 40 and the reagent station 46, and by way of one or more motors (e.g., a stepper motor or like device) the information acquisition device 54 may be translated to a position within the specimen dock 40 or the reagent station 46 for receiving a specimen rack 42 or a reagent rack 48. In this way, the information acquisition device 54 may scan the barcode and/or RFID antenna as the specimen containers 45 and/or reagent containers 52 are loaded into the sample preparation station 20 (see Col. 13, lines 26-60). It would have been obvious to one of ordinary skill in the art to modify the system of Hudson et al by incorporating an identifier on the assay vessel (as taught by DeWitte et al) for the benefit of providing an effective way to identify sample information (which is indicative of the compounds in the assay vessel) and report this sample information to the sample preparation module so that the vessels are properly and accurately prepared.
Claim 25 is rejected under 35 U.S.C. 103 as being unpatentable over Hudson et al and Steyaert et a as applied to claim 21 above, and further in view of Anderson (US PGPub 2008/0217254), cited in the IDS.
Regarding Claim 25, Hudson et al teaches the use of a trap and elute system (see [0050] and [0072]).
The combination of Hudson et al and Steyaert et al does not disclose a magnetic trap positioned in fluid communication with the open port sampling interface and situated to trap magnetic particles during transfer from the open sampling interface before introduction to an inlet of the mass spectrometer.
However, in the analogous art of devices and methods for capture of magnetic beads, Anderson teaches a parallel multichannel system is implemented allowing multiple sets of beads to be handled at once, resulting in a high-throughput capability to process samples. In parallel mode the system can employ microfluidics and multiple magnetic bead traps to create 8, 12, or 96 bead traps in a planar or cylindrical configuration, and includes microfluidic switching valves to connect the bead traps with aspiration probes inserted into the sample wells (from which beads binding target analytes at equilibrium are aspirated) (see [0052]). In addition, Anderson teaches that the magnetic bead traps effectively carry out a specific capture/elution process on magnetic beads under control of a computerized LC-MS/MS system (see [0067]). It would have been obvious to one of ordinary skill in the art to incorporate a magnetic trap into the system of Hudson et al for the benefit of enabling the magnetic bead traps effectively carry out a specific capture/elution process on magnetic beads under control of a computerized LC-MS/MS system.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Datwani et al (US PGPub 20190157061) discloses a system and method are provided for loading a sample into an analytical instrument using acoustic droplet ejection (“ADE”) in combination with a continuous flow sampling probe. An acoustic droplet ejector is used to eject small droplets of a fluid sample containing an analyte into the sampling tip of a continuous flow sampling probe, where the acoustically ejected droplet combines with a continuous, circulating flow stream of solvent within the flow probe. Fluid circulation within the probe transports the sample through a sample transport capillary to an outlet that directs the analyte away from the probe to an analytical instrument, e.g., a device that detects the presence, concentration quantity, and/or identity of the analyte (such as a mass spectrometer) (see abstract).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JENNIFER WECKER whose telephone number is (571)270-1109. The examiner can normally be reached 9:30AM - 6 PM EST M-F.
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/JENNIFER WECKER/ Primary Examiner, Art Unit 1797
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