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
Applicant’s reply filed on 1/15/26 is acknowledged. Claims 2, 6, 8, 13, 15-16, 18-20, 22 and 29-30 were canceled, and claim 32 was newly added. Claims 1, 3-5, 7, 9-12, 14, 17, 21, 23-28, 31 and 32 are pending and are under examination.
Response to Reply
Claim Rejections - 35 USC § 101
In response to applicant’s argument on p. 8-9 of the reply, the Office respectfully does not find applicant’s argument to be persuasive because the amended claim language, “processing the image with a processor configured to: perform perspective correction of the image; detect device features and determine a center of the DMF device: isolate a region of interest for each droplet by detecting contours and combining contour segments: convert each isolated region of interest to grayscale, flatten it to a one dimensional array, normalize pixel intensities to a full 8-bit range, and sort the pixel intensities from lowest to highest within the array: and determine a degree of agglutination for each droplet based on a slope of a gradient of the sorted pixel intensities within the array; and classifying the sample as containing or not containing the pre-selected analytes based on the determined degree of agglutination” does not appear to recite any elements which are significantly more than the abstract idea (step 2B). The amended claim language appears to be essentially the same claim language as previously recited in claim 1 with regard to the steps of the analyzer, except now, the claim language recites the functioning of the processor, which is broken down into more steps/instructions. Thus, the prior 35 U.S.C. 101 rejection is maintained and modified in light of applicant’s claim amendments.
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1, 3-5, 7, 9-12, 14, 17, 21, 23-28, 31 and 32 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. The claimed invention, in particular claim 1, recites “perform perspective correction of the image”. The claim language, “perspective correction” is mental process because it involves a concept, such as judgement, performed in the human mind. Also, the claim language, “determine a degree of agglutination for each droplet based on a slope of a gradient of the sorted pixel intensities within the array” is an abstract idea. The slope can either be done as a mental observation (steep slope or flat slope- see [0132] et seq. of applicant’s specification) or math (calculation y=mx+b or another regression). As shown in fig. 4B, a steep slope indicates agglutination and a flat slope indicates no agglutination. A user can observe the slope and make this determination as a mental process, or alternatively a user can compare slopes to a threshold and determine agglutination based on that comparison. See e.g., [133] of applicant’s specification. Regarding the “processing the image with a processor,” the claim language doesn’t change the outcome because [0103] of applicant’s specification recites a microprocessor or computer, which appears to be general purpose computing devices. see MPEP 2106.04(a)(2)(III).
This judicial exception is not integrated into a practical application because after the “classifying” step, then no action is taken. Therefore, there is no application, much less a particular practical application. The claim does recite various steps of agglutinating the sample by electrowetting and then capturing an image by a camera. However, this is just data gathering which is then used in the processing the image with a processor steps, and data gathering is insignificant extra-solution activity and not a particular practical application. See MPEP 2106.05(g). Also, performing the abstract idea on a general purpose computer does not integrate the exception into a particular practical application because a general-purpose computer is not a particular machine. See MPEP 2106.05(b)(1).
Claim 1 does not include additional elements that are sufficient to amount to significantly more than the judicial exception because providing a two-plate electrowetting digital microfluidic device (DMF) having a plurality of driving electrodes, loading a fluid sample, agglutinating the sample with an agglutination agent by electrowetting, and capturing an image of the DMF are well known. Because the claimed steps are well-understood, routine, conventional activity, the claims do not recite significantly more than the abstract idea.
Dependent claims 3-5, 7, 9-12, 14, 17, 21, 23-28, 31 and 32 all further refine the method steps of claim 1 and were considered, however, the subject matter does not affect the result established above.
Claim Rejections - 35 USC § 112
In light of applicant’s claim amendments, the prior rejection under 35 U.S.C. 112(a) is withdrawn, and a new rejection follows.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 32 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. The claim language, “the kit further comprises instructions for classifying the sample as containing or not containing the pre-selected analytes based on the determined degree of agglutination,” does not appear to be supported by the originally filed disclosure.
In light of applicant’s claim amendments, the prior rejections under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, are withdrawn, and new rejections follow.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 3-5, 7, 9-12, 14, 17, 21, 23-28, 31 and 32 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 rejected for indefiniteness because the claim merely recites a use, e.g., “using,” without any active, positive steps delimiting how this use is actually practiced. See MPEP 2173.05(q).
Claim 1 is rejected because “perspective correction” is unclear.
Claim 1 is rejected because “flatten it” is unclear. What does “it” refer to?
Claim 26 is rejected because “a microprocessor” raises an antecedent basis issue. Is this supposed to refer to the processor of claim 1?
Claim 28 is rejected because “a camera” raises an antecedent basis issue.
Claim 31 is rejected because the microprocessor and processor are unclear. Are these two different computing devices?
Claim Interpretation
The Office asserts that terms and phrases like “capable of” and “wherein” constitute recitations of intended use language for purposes of examination. The Office asserts that in the examined claims reciting such “capable of” language, the claim language that follows such recitations does not necessarily denote structure MPEP 2173.05(g). The functional limitation was evaluated and considered, for what it fairly conveys to a person of ordinary skill in the art. Similarly, a “wherein” clause may have a limiting effect on a claim if the language limits the claim to a particular structure. MPEP 2111.04. The determination of whether a “wherein” clause is a limitation in a claim depends on the specific facts of the case. While all words in each claim are considered in judging the patentability of the claim language, including functional claim limitations, not all limitations provide a patentable distinction.
During patent examination, the examined claims must be given their broadest reasonable interpretation consistent with the specification, unless a term has been given a special definition in the specification (“BRI”). See MPEP 2111.
Prior Art Rejection
In light of the claim amendments, the prior art rejection is modified.
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.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 3-5, 7, 9-12, 14, 17, 21, 23-28, 31 and 32 are rejected under 35 U.S.C. 103 as being unpatentable over Huff et al. (“Huff,” US Pub. No. 2018/0275088, previously cited and cited in IDS) in view of Hull et al. (“Hull,” US Pub. No. 2018/0333724, previously cited).
As to claim 1, Huff teaches a method of characterizing a sample to determine a presence or absence of pre-selected analytes by agglutination assays (e.g., [0498] recites such chips may be used for assaying blood agglutination, for example, determining blood type), comprising steps of:
providing a two-plate electrowetting digital microfluidic device (DMF) having a plurality of driving electrodes ([0314] et seq. recites array of electrodes 49, first substrate 63, second substrate 64);
loading a fluid sample containing the analytes ([0043] et seq.) and an agglutination agent ([0468] et seq., recites poly(4-vinyl pyridine)) onto separate driving electrodes (see MPEP 2112.01(II));
using electrowetting (e.g., [0150] et seq.) to bring droplets of the fluid sample in contact with droplets of the agglutination agent ([0468] et seq., recites poly(4-vinyl pyridine)) to produce an agglutinate;
using electrowetting to transport the droplets, including the agglutinate, to a plurality of locations on the DMF device (see MPEP 2122.01(II) and 2173.05(g)); and
capturing, by a camera positioned at an angle with respect to the DMF device, an image including the plurality of locations (e.g., [0361] et seq.).
Regarding claim 1, while Huff teaches in e.g., [0149], that DMF is based upon the micromanipulation of discontinuous fluid droplets within a reconfigurable network and complex instructions can be programmed by combining the basic operations of droplet formation, translocation, splitting, and merging; in e.g., [0359] et seq., the device 68 (fig. 9) is controlled by the processing component 60 that executes instructions (steps of a program) to perform at least some steps of the analyte analysis methods disclosed herein; in e.g., [0443], the DMF region may be used to transfer a droplet for analysis to a detection region where the droplet will be analysed optically, which may be an image analysis; and in e.g., [0361], a processor may also be implemented as a combination of computing devices, e.g., a combination of process with a camera (Huff’s teachings read on “processing the image with a processor configured to: perform perspective correction of the image; detect device features and determine a center of the DMF device; isolate a region of interest for each droplet by detecting contours and combining contour segments”; see [0482] et seq.), Huff does not specifically teach convert each isolated region of interest to grayscale, flatten it to a one-dimensional array, normalize pixel intensities to a full 8-bit range, and sort the pixel intensities from lowest to highest within the array: and determine a degree of agglutination for each droplet based on a slope of a gradient of the sorted pixel intensities within the array; and classifying the sample as containing or not containing the pre-selected analytes based on the determined degree of agglutination. Hull teaches in e.g., [0096] et seq., the device may be used to determine the presence of a cell or agglutinate contained in a pod deposited in a well. In e.g., [0108] et seq., a computer vision technique for detecting and/or measuring agglutination in a pod may be based at least in part on distribution of pixel darkness or grayscale intensity in an optical image of the pod. For example, as shown in FIG. 20B corresponding to a non-agglutinated pod, a histogram of grayscale pixel darkness in an optical image of the pod may generally approximate a low, broad bell curve. This low, broad bell curve generally corresponds to the distributed reagent particles depicted in the optical image with pixels having a broad, lower range of individual grayscale darkness. In contrast, as shown in FIG. 21B corresponding to an agglutinated pod, a histogram of grayscale pixel darkness in an optical image of the pod may generally approximate a “sharp peaked” curve. This “sharp peaked” curve generally corresponds to the larger, clumped reagent particles collectively depicted in the optical image with pixels having a narrower, higher range of grayscale darkness. Thus, the shape of the pixel grayscale histogram for an image of a pod may be analyzed in order to determine whether agglutination is present in the pod. Additionally, Hull teaches in [0113] et seq., FIGS. 22-23 are exemplary images and data illustrating camera-based detection of non-agglutination and agglutination in pods. In particular, FIGS. 22A and 23A are camera images of pods including at least antibody-coated beads specific to immunoglobulin G (IgG). It would have been obvious to one having ordinary skill in the art, before the effective filing date of the claimed invention, to convert each isolated region of interest to grayscale, flatten it to a one-dimensional array, normalize pixel intensities to a full 8-bit range, and sort the pixel intensities from lowest to highest within the array, and determine a degree of agglutination for each droplet based on a slope of a gradient of the sorted pixel intensities within the array; and classify the sample as containing or not containing the pre-selected analytes based on the determined degree of agglutination because it would enable analyte measurement in a variety of applications (e.g., drug discovery, research, diagnostic, etc.) (e.g., [0106] of Hull).
Furthermore, regarding claim 1, while Huff teaches graphs with x-axis and y-axis in fig. 13, 15A-B, 24A -C, 28-34 et seq., Huff does not specifically teach the sorted pixel-intensity array comprises a graph of pixel intensity on x-axis versus the number of pixels on y-axis. Hull teaches in fig. 20B, for example, a graph having an x-axis labeled pixel darkness, which is also described as pixel grayscale intensity values in fig. [0040] et seq., and a y-axis labeled as number of pixels. It would have been obvious to one having ordinary skill in the art, before the effective filing date of the claimed invention, to have a sorted pixel-intensity array comprising a graph of pixel intensity on x-axis versus the number of pixels on y-axis because it would make the computer vision technique more convenient to determine whether agglutination is present in the pod based on the shape of the pixel grayscale graph (e.g., [0108-0109] of Hull).
As to claim 3, Huff does not specifically teach determining an amount of agglutination of the analytes, Hull teaches in e.g., [0110] et seq., a measurement of the degree or amount of agglutination may be performed. For example, detection of fewer, larger clumps (which may be indicated by more pixels having a darker grayscale intensity, for example) may be indicative of greater agglutination. It would have been obvious to one having ordinary skill in the art, before the effective filing date of the claimed invention, to determining an amount of agglutination of the analytes because it would provide helpful analyte measurements for diagnostic applications.
As to claims 4 and 7, Huff teaches surfactants in e.g., [0418], and Hull teaches surfactants in e.g., [0048].
As to claim 5, while Huff teaches in [0488], DMF electrodes may be operated to move the sample droplet to a region in the first chamber having a reagent (e.g., a staining reagent, such as, a dye that binds to nucleic acid, e.g., acridine orange, ethidium bromide, TOTO, TO-PRO, or SYTOX) disposed in a dry form or in form of a droplet. The sample droplet may be mixed with the reagent to provide uniform distribution of the reagent in the sample droplet; in [0321], the electrodes in the microfluidics module may optionally be coated with a dielectric material. A hydrophobic coating may also be provided on the dielectric; and in [0348], a dielectric insulator coated with a hydrophobic may be coated over the electrodes to decrease the wettability of the surface and to add capacitance between the droplet and the control electrodes (the patterned array of electrodes), Huff does not specifically teach coating the electrodes with pre-dried surfactant, which is solubilized with fluid sample. However, Huff teaches in [0147], some components can be in solution or lyophilized for reconstitution for use in an assay. It would have been obvious to one having ordinary skill in the art, before the effective filing date of the claimed invention, to solubilize a pre-dried surfactant coated on the electrodes because it would be desirable to control the wettability of the surface, and to control the capacitance between the droplet and the control electrodes.
As to claim 9, Huff teaches binding members, such as antibodies, are in liquid form in [0017], [0187] et seq. See MPEP 2122.01(II). Also see e.g., [0046] et seq. of Hull for liquid agglutination agents.
As to claim 10, Huff teaches in e.g., [0205], the single droplet may be agitated to facilitate mixing of the sample with the first binding member (e.g., antibodies can be agglutination agents under MPEP 2122.01(II); and electrowetting in e.g., [0209] of Huff.
As to claims 11-12, Huff teaches a chemical agglutination agent, poly(4-vinylpyridine), in [0468]; and a biological agglutination agent, antibodies in [0017] et seq.
As to claim 14, Huff teaches lectins and antibodies in [0232], which recites suitable target analyte/binding member complexes can include, but are not limited to, antibodies/antigens, antigens/antibodies, receptors/ligands, ligands/receptors, proteins/nucleic acid, enzymes/substrates and/or inhibitors, carbohydrates (including glycoproteins and glycolipids)/lectins and/or selectins, proteins/proteins, proteins/small molecules, etc. See MPEP 2122.01(II).
As to claim 17, see [0232] et seq. of Huff, and [0106] of Hull. See motivation statement above.
As to claim 21, see e.g., [0498] et seq. of Huff.
As to claim 23, see e.g., [0071] et seq. of Huff.
As to claim 24, Huff teaches a chemical agglutination agent, poly(4-vinylpyridine), in [0468]. See MPEP 2122.01(II).
As to claims 25 and 27, Huff teaches a two-plate electrowetting DMF device, comprising: a first plate, a second plate spaced from said first plate, one of said first and second plates having a plurality of driving electrodes (e.g., [0314] et seq. recites array of electrodes 49, first substrate 63, second substrate 64); and teaches in [0147], some components can be in solution or lyophilized for reconstitution for use in an assay; in [0183], the solid support on which the first binding member is immobilized may be stored in dry form or in a liquid; in [0434], one or more of the components of the kit can be lyophilized, in which case the kit can further comprise reagents suitable for the reconstitution of the lyophilized components; and in [0488], DMF electrodes may be operated to move the sample droplet to a region in the first chamber having a reagent (e.g., a staining reagent, such as, a dye that binds to nucleic acid, e.g., acridine orange, ethidium bromide, TOTO, TO-PRO, or SYTOX) disposed in a dry form or in form of a droplet. Huff teaches surfactants in e.g., [0418], and agglutination agents, antibodies in [0017] et seq. However, Huff does not specifically teach the surfactant and agglutination agent are in pre-dried form. It would have been obvious to one having ordinary skill in the art, before the effective filing date of the claimed invention, to have a pre-dried surfactant and a pre-dried agglutination agent because it would be desirable to preserve sensitive surfactants and agglutination agents before use.
As to claim 26, Huff teaches a microprocessor (e.g., processor in [0348] et seq.) connected to a power supply (e.g., power source in [0314] et seq.) and said plurality of driving electrodes (e.g., electrodes in [0314] et seq.) and programmed with instructions (e.g., this is considered intended use and/or functional claim language, see MPEP 2173.05(g)) to provide power to said driving electrodes in a pre-selected pattern for moving droplets of fluid sample being studied for presence of pre-selected analytes located therein and an agglutination agent over the electrodes (e.g., [0314] et seq.).
As to claim 28, Huff teaches a camera (e.g., [0361] et seq.) positioned so that its field of view encompasses the DMF device, and wherein said images are analyzed for (e.g., “for” is an intended use and/or functional term, see MPEP 2173.05(g)) determining an amount of agglutination of the analytes caused by the agglutination agent using image analysis of the fluid sample.
As to claim 31, Huff teaches a kit, comprising: a two-plate electrowetting digital microfluidic device (DMF) having a plurality of driving electrodes (e.g., [0314] et seq. recites array of electrodes 49, first substrate 63, second substrate 64); a microprocessor (e.g., processor in [0348] et seq.) connected to a power supply (e.g., power source in [0314] et seq.) and said plurality of driving electrodes (e.g., electrodes in [0314] et seq.) and programmed with instructions to provide power to said driving electrodes in a pre-selected pattern for moving droplets of the fluid sample and the agglutination agent over the electrodes (e.g., this is considered intended use and/or functional claim language, see MPEP 2173.05(g); [0314] et seq.); and a surfactant (e.g., [0418]) for (e.g., “for” is an intended use and/or functional term, see MPEP 2173.05(g) placement on one of said two plates; and an agglutination agent ([0017] et seq.) for (e.g., “for” is an intended use and/or functional term, see MPEP 2173.05(g) placement on one of said two plates; a camera (e.g., [0361] et seq.) positioned at an angle with respect to the DMF device so that its field of view encompasses the DMF device.
Regarding claim 31, Huff does not specifically teach the processor is to determine a degree of agglutination for each droplet. Hull teaches in e.g., in [0106], computer vision techniques may be used to detect and measure agglutination within a pod, thereby enabling analyte measurement in a variety of applications (e.g., drug discovery, research, diagnostic, etc.). For example, pods may include reagent particles (e.g., antibody-coated beads) specific to a target analyte that may or may not be present in a particular pod. If the analyte is not present in a pod, agglutination (clumping) between the analyte and the reagent particles will not occur. In contrast, if the analyte is present in a pod, such agglutination will occur. It would have been obvious to one having ordinary skill in the art, before the effective filing date of the claimed invention, to visually characterize any agglutinate formed because it would provide helpful analyte measurements for diagnostic applications.
As to claim 32, see e.g., [0149] et seq. of Huff.
Response to Arguments
Applicant's arguments filed 1/15/26 have been fully considered but they are not persuasive. See the modified rejections above, and the prior response to arguments filed 7/15/25.
Conclusion
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 LORE RAMILLANO JARRETT whose telephone number is (571)272-7420. The examiner can normally be reached Monday to Friday.
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/LORE R JARRETT/Primary Examiner, Art Unit 1797
5/14/2026
Prosecution Insights