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 .
Status of Claims
Claims 1, 14 and 20 have been amended. Claims 1-20 are pending and have been examined.
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 1-19 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 is indefinite because it recites in the preamble “a solution comprising a plurality of particles in a vial” and then states agitating the vial and dispersing into the vial a first volume of buffer to suspend the plurality of particles to reduce binding of the particles but it is unclear at what point the particles are incorporated into the vial. For example, are the particles in the vial during the first agitation step or are they incorporated with the buffer to suspend the particles.
Claim 1 is confusing because it states “to reduce binding of the plurality of particles to one another” and it is unclear if the particles include functionalization that could allow binding to one another that is supposed to be prevented or if the binding is referring to clumping/aggregating of the particles.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 1-12 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Renick et al. (US 2020/0164322, Pub Date: 05/28/2020) in view of Tsao et al. (US 2014/0274778, Pub Date: 09/18/2014, hereinafter “Tsao”).
Regarding claims 1-3, Renick teaches throughout the publication apparatuses and systems for mixing liquids and suspensions that include vessels that improve mixing (paragraph 0002). More specifically, Renick teaches a method for preparing a solution comprising a plurality of particles in a vial (paragraph 0013, uniformly suspending particulates in a cylindrical vessel), the method comprising: agitating the vial at a first predetermined mixing speed; and dispersing, into the vial, during the agitating, a first volume of buffer solution at a first predetermined dispensing rate to suspend the plurality of particles in the solution (paragraph 0093, turbulent mixing action may keep even heavy particulates in uniform suspension – see Figure 7B, paramagnetic beads uniformly suspended and not bound to one another while suspended in a wash reagent (buffer); paragraph 0094, gentle yet vigorous mixing which may allow materials to be added while still mixing or uniformly suspending particulates; paragraph 0095, vessels are compatible with robotic work stations for sequential addition of materials to the vessel while mixing – robotic dispensing reads on the broadly recited predetermined dispensing rate; paragraph 0100, setting of control values, including speed of mixing rotation, duration of rotation, each of which may be individually determined for each application and particulate; paragraph 0115, introducing a particulate component to a vessel while turbulence occurs).
While Renick teaches that particles can be various types of particulates (paragraph 0101), one example being paramagnetic beads (paragraph 0096), as in instant claim 2, the reference fails to teach that particles of the plurality of particles comprise a unique identifying feature comprising one or more unique bar codes.
Tsao teaches throughout the publication compositions comprising beads with unique identifiers for storing information about a multiplex assay (abstract). More specifically, Tsao teaches that the individual beads can be identified by marking them with an encoded pattern comprising a high contrast and high signal to noise barcode image, as in instant claim 3 (paragraph 0047).
It would have been prima facie obvious to one having ordinary skill in the art at the time the invention was filed to modify the paramagnetic beads in the method of Renick by marking them with a barcode image as taught by Tsao because it would have been desirable to facilitate identification by an image processor (Tsao, paragraph 0047) and utilize beads that are useful for conducting high throughput and multiplex chemical and biological assays, since, by virtue of each bead containing a unique identifier, the identity of any individual capture agent attached to the bead can be readily ascertained (Tsao, paragraph 0015).
Regarding claim 4, Renick in view of Tsao teach the method wherein particles of the plurality of particles further comprise a binding member corresponding to the unique identifying feature (Tsao, paragraphs 0009, 0015 and 0108).
Regarding claim 5, Renick teaches the method wherein the agitating the vial at the first predetermined mixing speed comprises moving the vial in an orbital pattern (paragraph 0078).
Regarding claim 6, although Renick in view of Tsao does not specifically teach the method wherein moving the vial in the orbital pattern comprises moving a center of the vial up to 3 millimeters from a horizontal center, it has long been settled to be no more than routine experimentation for one of ordinary skill in the art to discover an optimum value for a result effective variable. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation” Application of Aller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). “No invention is involved in discovering optimum ranges of a process by routine experimentation.” Id. at 458, 105 USPQ at 236-237. The “discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art.” Since applicant has not disclosed that the specific limitations recited in instant claim 6 are for any particular purpose or solve any stated problem, and the prior art teaches that the mixing can have many configurable parameters to improve assay performance. Absent unexpected results, it would have been obvious for one of ordinary skill to discover the optimum workable ranges of the methods disclosed by the prior art by normal optimization procedures known in the sample preparation art.
Regarding claim 7, Renick teaches the method wherein the first predetermined mixing speed is between 400 revolutions per minute and 600 revolutions per minute (paragraph 0119).
Regarding claim 8, while Renick teaches that the vessel has no restrictions concerning liquid volume during either addition of material or removal of solutions (paragraph 0096), the references does not specifically teach the method wherein the first volume of buffer solution is between 180 microliters of buffer solution and 220 microliters of buffer solution, it has long been settled to be no more than routine experimentation for one of ordinary skill in the art to discover an optimum value for a result effective variable. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation” Application of Aller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). “No invention is involved in discovering optimum ranges of a process by routine experimentation.” Id. at 458, 105 USPQ at 236-237. The “discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art.” Since applicant has not disclosed that the specific limitations recited in instant claim 8 are for any particular purpose or solve any stated problem, and the prior art teaches that the volumes may be varied within the scope and spirit of the invention. Absent unexpected results, it would have been obvious for one of ordinary skill to discover the optimum workable ranges of the methods disclosed by the prior art by normal optimization procedures known in the sample preparation art.
Regarding claim 9, while Renick in view of Tsao do not specifically teach the method wherein the first predetermined dispensing rate is between 270 microliters of buffer solution per second and 330 microliters of buffer solution per second, it has long been settled to be no more than routine experimentation for one of ordinary skill in the art to discover an optimum value for a result effective variable. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation” Application of Aller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). “No invention is involved in discovering optimum ranges of a process by routine experimentation.” Id. at 458, 105 USPQ at 236-237. The “discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art.” Since applicant has not disclosed that the specific limitations recited in instant claim 9 are for any particular purpose or solve any stated problem, and the prior art teaches that the procedure variables may be varied within the scope and spirit of the invention. Absent unexpected results, it would have been obvious for one of ordinary skill to discover the optimum workable ranges of the methods disclosed by the prior art by normal optimization procedures known in the sample preparation art.
Regarding claim 10, although Renick in view of Tsao do not specifically teach the method wherein the first volume of buffer solution comprises 200 microliters of buffer solution, and wherein the first predetermined dispensing rate comprises 300 microliters of buffer solution per second, it has long been settled to be no more than routine experimentation for one of ordinary skill in the art to discover an optimum value for a result effective variable. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation” Application of Aller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). “No invention is involved in discovering optimum ranges of a process by routine experimentation.” Id. at 458, 105 USPQ at 236-237. The “discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art.” Since applicant has not disclosed that the specific limitations recited in instant claim 10 are for any particular purpose or solve any stated problem, and the prior art teaches that the procedure variables may be varied within the scope and spirit of the invention. Absent unexpected results, it would have been obvious for one of ordinary skill to discover the optimum workable ranges of the methods disclosed by the prior art by normal optimization procedures known in the sample preparation art.
Regarding claim 11, Renick teaches the method wherein the buffer solution comprises a read buffer solution (paragraph 0267).
Regarding claim 12, Renick teaches the method wherein the method further comprises: detecting, after the agitating and the dispersing, an assay read signal corresponding to at least one of the particles of the plurality of particles, wherein detecting the assay read signal occurs within a predetermined time period after completing the agitating and the dispersing (paragraph 0116).
Regarding claim 20, Renick teaches throughout the publication apparatuses and systems for micing liquids and suspensions that include vessels that improve mixing (paragraph 0002). More specifically, Renick teaches a method for preparing a solution comprising a plurality of particles in a vial (paragraph 0013, uniformly suspending particulates in a cylindrical vessel), the method comprising: agitating the vial at a first predetermined mixing speed; and dispersing, into the vial, during the agitating, a first volume of buffer solution at a first predetermined dispensing rate to suspend the plurality of particles in the solution (paragraph 0093, turbulent mixing action may keep even heavy particulates in uniform suspension – see Figure 7B, paramagnetic beads uniformly suspended and not bound to one another while suspended in a wash reagent (buffer); paragraph 0094, gentle yet vigorous mixing which may allow materials to be added while still mixing or uniformly suspending particulates; paragraph 0095, vessels are compatible with robotic work stations for sequential addition of materials to the vessel while mixing – robotic dispensing reads on the broadly recited predetermined dispensing rate; paragraph 0100, setting of control values, including speed of mixing rotation, duration of rotation – each of which may be individually determined for each application and particulate; paragraph 0115, introducing a particulate component to a vessel while turbulence occurs). Furthermore, Renick teaches that computer systems operably coupled to at least one motor to drive the spin vessel, such as a programmable processor configured for running one or more logic function with respect to a program stored in a memory module coupled to the processor, with programs including speed regulation and setting of control values including the predetermined parameters (paragraphs 0099-0100).
While Renick teaches that particles can be paramagnetic beads, the reference fails to teach that particles of the plurality of particles comprise a unique identifying feature.
Tsao teaches throughout the publication compositions comprising beads with unique identifiers for storing information about a multiplex assay (abstract). More specifically, Tsao teaches that the individual beads can be identified by marking them with an encoded pattern comprising a high contrast and high signal to noise barcode image (paragraph 0047).
It would have been prima facie obvious to one having ordinary skill in the art at the time the invention was filed to modify the paramagnetic capture beads in the method and computer programs to execute the driving of the spin vessel of Renick by marking them with a barcode image as taught by Tsao because it would have been desirable to facilitate identification by an image processor (Tsao, paragraph 0047) and utilize beads that are useful for conducting high throughput and multiplex chemical and biological assays, since, by virtue of each bead containing a unique identifier, the identity of any individual capture agent attached to the bead can be readily ascertained (Tsao, paragraph 0015).
Claim(s) 13-14 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Renick et al. (US 2020/0164322, Pub Date: 05/28/2020) in view of Tsao et al. (US 2014/0274778, Pub Date: 09/18/2014, hereinafter “Tsao”), as applied to claim 1 above (hereinafter “Modified Renick”), and further in view of Honkanen et al. (US 2013/0034284, Pub Date: 02/07/2013).
Regarding claims 13-14, Modified Renick teaches the method as described above and further teaches transferring a sample of the prepared solution onto a surface, wherein the prepared solution comprises the first volume of buffer solution and the plurality of particles (Renick, paragraph 0152). However, Modified Renick does not teach the method comprising generating a composite image of the transferred sample of prepared solution, wherein the composite image comprises a plurality of images of the transferred sample of prepared solution; and based on the generated composite image, determining a parameter of the transferred sample of prepared solution, wherein generating the composite image of the transferred sample of prepared solution further comprises stitching the plurality of images of the transferred sample of prepared solution into the composite image of the transferred sample of prepared solution.
Honkanen teaches throughout the publication the use of composite images (abstract). More specifically, Honkanen teaches obtaining multiple images of pixels representing light intensity output from an assay, wherein the light intensity output indicates a presence and an amount of a substance within wells of a test plate, and wherein the multiple images of pixels are generated by using a detector to detect the light intensity of the pixels of the wells using a standard exposure time; and generating a composite image using the multiple images of pixels, wherein the method further comprises using the composite image to determine the presence and the amount of the substance within the wells (paragraphs 0011-0012). Furthermore, Honkanen teaches the method further comprises obtaining one or more of the composite images; combining the pixels in one or more of the composite images with pixels at a same relative position in other composite images to generate a template image of the wells, wherein the composite pixels at the same relative positions represent anticipated positions of printed features in a test plate; and using the template image to find a location of a feature within the test plate, wherein the location indicates presence and amount of a substance in the test plate (paragraph 0015).
It would have been prima facie obvious to one having ordinary skill in the art at the time the invention was filed to incorporate within the method of Modified Renick, the generation of a composite image to determine a parameter of the transferred solution as well as stitching the plurality of images into the composite image as taught by Honkanen because it would have been desirable to provide composite images with enhanced dynamic range that results in more accurate, reliable and efficient biological analyses (Honkanen, paragraph 0010).
Regarding claim 19, Modified Renick teaches wherein the method further comprises: transmitting instructions that cause a graphical user interface to display a graphical representation of the determined parameter of the transferred sample of prepared solution (Renick, paragraphs 0099-0100).
Claim(s) 15 is rejected under 35 U.S.C. 103 as being unpatentable over Renick et al. (US 2020/0164322, Pub Date: 05/28/2020) in view of Tsao et al. (US 2014/0274778, Pub Date: 09/18/2014, hereinafter “Tsao”) and Honkanen et al. (US 2013/0034284, Pub Date: 02/07/2013), as applied to claim 13 above (hereinafter “Modified Renick”), and further in view of Liffman et al. (US 2015/0253224, Pub Date: 09/10/2015).
Regarding claim 15, Modified Renick teaches the method as described above but fails to specifically teach wherein determining a parameter of the transferred sample of prepared solution comprises counting the plurality of particles in the transferred sample of prepared solution.
Liffman teaches throughout the publication an automated system configured to dispense a sample (abstract). More specifically, Liffman teaches forming composite images and using complete counts based on the images, from which parameters associated from the count can be determined using software inside a compute (paragraph 0118).
It would have been prima facie obvious to one having ordinary skill in the art to incorporate within the method of Modified Renick, using a count from the composite images to determine a desired parameter as taught by Liffman because it would have been desirable to provide for enhanced analysis of normal and abnormal particle based on the formed composite images (Liffman, paragraph 0117-0118).
Claim(s) 16-18 are rejected under 35 U.S.C. 103 as being unpatentable over Renick et al. (US 2020/0164322, Pub Date: 05/28/2020) in view of Tsao et al. (US 2014/0274778, Pub Date: 09/18/2014, hereinafter “Tsao”), Honkanen et al. (US 2013/0034284, Pub Date: 02/07/2013) and Liffman et al. (US 2015/0253224, Pub Date: 09/10/2015), as applied to claim 15 above (hereinafter “Further Modified Renick”), and further in view of Fan et al. (US 2016/0289669, Pub Date: 10/06/2016).
Regarding claim 16, Further Modified Renick teaches the method as described above but fails to teach that the particle counting comprises detecting an edge of a particle in the composite image; and based at least in part on detecting an edge of the particle in the composite image, determining a presence of at least one particle in the composite image.
Fan teaches throughout the publication systems for determining the number of target molecules in a sample (paragraph 0007). More specifically, Fan teaches that the instrument system will comprise functionality for providing image processing and analysis capability such as automated edge detection and object identification for identifying cells and beads in the image (paragraph 0431). After the edges are detected, desired particles can be identified (paragraph 0522).
It would have been prima facie obvious to one having ordinary skill in the art at the time the invention was filed to incorporate within the method of Further Modified Renick, edge detection for particle identification as taught by Fan because it would have been desirable to utilize an automated method that can provide further information for identifying objects of interest in an image (Fan, paragraphs 0431).
Regarding claims 17-18, Further Modified Renick in view of Fan teaches the method wherein the method further comprises: comparing the determined presence of at least one particle in the composite image to a previously generated image of the transferred sample of prepared solution (Honkanen, paragraph 0034) and further wherein the previously generated image of the transferred sample of prepared solution comprises one or more images of the transferred sample of prepared solution using ultraviolet light (Fan, paragraph 0421).
Response to Arguments
Applicant’s arguments filed 12/10/2025 have been considered but are found to be moot in view of the new grounds of rejection applied to the newly amended claims. While Godsey does not teach a mixing method for reducing binding of the plurality of particles to one another (as currently amended), Renick specifically teaches a mixing method to maintain uniformity of particles in suspension (see rejection above and for example, paragraphs 0078-0079). As such, the claims remain unpatentable, as described above.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Rong et al. teaches a magnetic chaotic mixer for achieving uniform distribution of biocells on magnetic beads (see pages 335-338).
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to REBECCA M GIERE whose telephone number is (571)272-5084. The examiner can normally be reached M-F 8:30-4:30.
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/REBECCA M GIERE/Primary Examiner, Art Unit 1677