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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 04/20/2026 has been entered.
Response to Amendment
Applicant amendments filed 04/20/2026 have been entered. Applicant amendments overcomes the previous claim objection and 112(b) rejections set forth in the Office Action mailed 01/22/2026, the previous claim objection and 112(b) rejections are withdrawn.
Status of Claims
Claims 56-59, 69-73, 75-83 remain pending in the application.
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 56-59, 69-73, 75-83 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 56 lines 7-8 recites “and identify a total number of positive microparticle complexes from the cell-microparticle co-culture” where it is unclear because lines 5-6 now recites “direct the cytometry system to identify and count a total number of microparticle complexes and a number of positive microparticle complexes”. Is the identification described in lines 7-8 a different identification step?
For examination, it will be interpreted that lines 7-8 are describing the same identification as described in lines 5-6.
Lines 11-12 recites “wherein each positive microparticle complex comprises a microparticle complex that further comprises a secreted biomarker bound to the capture ligand,” where it is unclear if the microparticle complex is the same or different from the microparticle complex described prior.
For examination, it will be interpreted that they are the same microparticle complex.
It is suggested to amend lines 11-12 to recite “wherein each positive microparticle complex comprises to the capture ligand,” Please note that this is how it is phrased in claim 80.
Lines 9-17 all describe the microparticle complex and positive microparticle complex, where it is unclear if lines 9-17 are things that the processor does. This is due to lines 3-4 reciting “a non-transitory computer readable medium comprising instructions that cause the processor to:” and then line 5 describes “direct the cytometry system to identify and count”, followed by lines 9-17, and then lines 18-19 which describe “calculate a percentage of the positive microparticles among the total number of microparticle complexes.”
For examination, because the cell-microparticle co-culture is not positively recited as a part of the cytometry system lines 9-17 will not be considered as required parts of the cytometry system. Please see 103 rejection below for more detail.
Claims 57-59, 69-73, 75-79 are rejected by virtue of being dependent on a rejected claim.
Claim 80 lines 10-17 describe the microparticle complex and positive microparticle complex, where it is unclear if lines 10-17 are all things that the processor does. This is due to lines 5-6 reciting “a non-transitory computer readable medium comprising instructions that cause the processor to:” and then line 7 describes “direct the cytometry system to identify and count”, followed by lines 10-17, and then lines 18-19 describe “calculate the percentage of the positive microparticle complexes among the total number of microparticle complexes.”
Further, due to the phrasing described above it is unclear if the processor is causing the secretion of the biomarker from the cell due to a stimulant. Is the processor causing a stimulant to be released? Therefore, for examination it will be interpreted that the biomarker being detected has been secreted.
Line 16 recites “secreted from a cell” where it is unclear if this cell is the same or different from the cell-microparticle co-culture described on line 2. From line 2, it is believed that a cell-microparticle co-culture will include at least a cell and microparticle, where now on line 16 it is unclear if this cell is the same or different from that described above.
Claims 81-83 are rejected by virtue of being dependent on a rejected claim.
Claim 81 recites “for co-culturing cells and microparticles in the cell-microparticle co-culture.” where it is unclear because claim 80 appears to be reciting both a cell and microparticle from “a cell-microparticle co-culture”.
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.
Claim(s) 56, 58, 69-73 is/are rejected under 35 U.S.C. 103 as being unpatentable over Chu (US-2006/0240444-A1) as evidenced by Ward (US-5627037-A), and in view of Beckman Coulter Cytomics FC 500 MPL flow cytometry system 2003, herein Beckman Coulter, and Mohapatra (US-2007/0036867-A1).
Regarding claim 56, Chu teaches a cytometry system (Beckman Coulter Cytomics FC 500 MPL Flow Cytometry System), comprising ([0049]):
a non-transitory computer readable medium comprising instructions that cause the processor to ([0049] see that the Beckman Coulter Cytomics FC 500 Flow Cytometry system can perform automated 5-color analysis using either single or dual laser excitation, where therefore the system will have non-transitory computer readable medium comprising instructions):
direct the cytometry system (Beckman Coulter Cytomics FC 500 MPL Flow Cytometry System) to identify and count a total number of microparticle complexes and a number of positive microparticle complexes in a sample obtained from a cell- microparticle co-culture, and identify a total number of positive microparticle complexes from the cell- microparticle co-culture ([0034] see flow cytometry relies on the passage of a stream of bead suspension where as each bead passes through a beam-sensor region the resulting scattered and fluorescent light is detected, the detected optical signals are used by the instrumentation to identify the subgroup to which each bead belongs along with the presence and amount of label so that individual bead results are achieved),
It is evidenced by Ward that for flow cytometers, a sample is run through the cytometer where fluorescence and scatter data for each event is recorded, where a fluorescence trigger is set so that all microparticles and cells to be counted meet or exceed the trigger level, where then the events recorded are reanalyzed (Ward; column 7 lines 39-54).
Therefore, from [0034] of Chu and the evidence of Ward, one skilled in the art would find it obvious that the flow cytometer will be counting all the microparticles that pass through, where during analysis for the presence and amount of label will indicate if the microparticle is positive.
Please note that the cell-microparticle co-culture has not been positively recited in the claim, and therefore is not a part of the claimed cytometry system. Therefore the limitation “direct the cytometry system to identify and count a total number of microparticle complexes and a number of positive microparticle complexes in a sample obtained from a cell- microparticle co-culture, and identify a total number of positive microparticle complexes from the cell- microparticle co-culture,” is directed to the function of the apparatus and/or the manner of operating the apparatus, all the structural limitations of the claim has been disclosed by Chu and the apparatus of Chu is capable of identifying total number of microparticle complexes and total number positive microparticle complexes. As such, it is deemed that the claimed apparatus is not differentiated from the apparatus of Chu (see MPEP §2114).
In other words, the system of Chu does need to be identifying a total number of microparticle complexes and a total number of positive microparticle complexes, however the positive complexes coming from a cell-microparticle co-culture is not required.
While Chu describes that a Beckman Coulter Cytomics FC 500 MPL Flow Cytometry System is used, Chu does not describe the specific components of this system.
As provided by the Beckman Coulter data sheet on page 5 under the part number it recites MPL hardware field upgrade includes MPL hardware, MXP software, Microsoft Excel software, Multi-file analysis software and 40-tube rack.” along with specifications for the computer, cytometer and MPL, monitor, power supply, and power. Therefore, one skilled in the art would find it obvious that the Beckman Coulter Cytomics FC 500 MPL Flow Cytometry System of Chu will include a processor.
Chu does not teach calculate a percentage of the positive microparticle complexes among the total number of microparticle complexes.
In the analogous art of flow cytometry, Mohapatra teaches the quantification of transfection efficiency of chitosan (Mohapatra; [0049]).
Specifically, Mohapatra teaches where transfected cells are harvested and scored for GFP-positive cells by flow cytometry with appropriate gating, where the percentage of positive events is calculated as the events within the gate divided by the total number of events then subtracting percentage of control samples (Mohapatra; [0049]).
It would have been obvious to one skilled in the art to modify the analysis (and thus instructions) of Chu such that it includes the step of calculating the percentage of positive microparticles as taught by Mohapatra because Mohapatra teaches that in flow cytometry it is desirable and effective to calculate the percentage of positive events (Mohapatra; [0049]).
Examiner further finds that the prior art included each element claimed (as set forth above), although not necessarily in a single prior art reference, with the only difference between the claimed invention and the prior art being the lack of actual combination of the elements within a single reference. Moreover, an ordinarily skilled artisan could have combined the elements as claimed by known methods (e.g., adding the calculation of percentage of positive events to the analysis), and that in combination, each element merely would have performed the same function as it did separately (i.e., the flow cytometer will still be analyzing and recording fluorescence), and an ordinarily skilled artisan would have recognized that the results of the combination were predictable.
Therefore, pursuant to MPEP §2143 (I), Examiner concludes that it would have been obvious to an ordinarily skilled artisan to combine the analysis of reference Chu with the analysis of calculating the percentage of positive events of reference Mohapatra, since the result would have been predictable.
Please note that because the cell-microparticle co-culture has not been positively recited, and the microparticle complex and positive microparticle complex have not been positively recited, the following limitations are not required because the cell-microparticle co-culture, microparticle complex, and positive microparticle complex are not a part of the claimed system:
wherein each microparticle complex comprises an ID coded microparticle and a capture ligand, where the ID code allows identification of all microparticle complexes,
wherein each positive microparticle complex comprises a microparticle complex that further comprises a secreted biomarker bound to the capture ligand, and a labeled detection reagent bound to the secreted biomarker, where the labeled detection reagent allows identification of the positive microparticle complexes,
wherein the labeled detection reagent is specific for the secreted biomarker, and
wherein the secreted biomarker has been secreted from a cell in response to stimulation by a stimulant;
Regarding claim 58, modified Chu teaches the cytometry system of Claim 56. Chu further teaches wherein the cytometry system is a flow cytometry system (see claim 56 supra).
Regarding claim 69, modified Chu teaches the cytometry system of Claim 56.
The positive microparticles that comprise the biomarker are not positively recited as part of the system, therefore the limitation “wherein the biomarker is selected from the group consisting of: a cytokine, an immunoglobulin, a hormone, a growth factor, an enzyme, a protease, a protein, an allergen, a peptide, a nucleic acid, a drug, a cluster differentiation (CD) molecule, a tumor marker, a receptor, and combinations thereof.” is considered to be met.
Please note that [0004] of Chu describes that a target molecule (what binds to the coating antibody on the bead) may be a protein or a nucleic acid.
Regarding claim 70, modified Chu teaches the cytometry system of Claim 56.
The stimulant is part of the intended use of the system, please see claim 56 supra for further explanation. Further, the positive microparticles that comprise a biomarker nor the stimulant have been positively recited as part of the system, therefore the limitation “wherein the stimulant is selected from the group consisting of: an antigen, a ligand, a protein, a glycoprotein, a peptide, a lectin, a nucleic acid, a cell, a sub-cellular component, a microorganism, an allergen, a drug, an interferon, a chemokine, an interleukin, a CD molecule, a chemical compound, an agonist, an antagonist, and combinations thereof.” is considered to be met.
Regarding claim 71, modified Chu teaches the cytometry system of Claim 56.
The cell has not been positively recited as part of the system, where therefore the limitation “wherein the cell is of a type selected from the group consisting of: a peripheral blood mononuclear cell (PBMC), a white cell, a tumor cell, a stem cell, an immune cell, a lymphocyte, a T cell, a B cell, a natural killer (NK) cell, a natural killer T (NKT) cell, a macrophage, a dendritic cell, a monocyte, a granulocyte, an epithelial cell, an endothelial cell, and a platelet.” is considered to be met.
However, please see [0007] of Chu which describes that a target molecule associated with a disorder refers to molecules produced by a diseased cell (tumor cell).
Regarding claim 72, modified Chu teaches the cytometry system of Claim 56.
The microparticle complexes have not been positively recited as a part of the system, therefore the limitation “wherein the microparticle comprises a material selected from the group consisting of: latex, polystyrene, silica, a magnetic material, a paramagnetic material, and combinations thereof.” is considered to be met.
However, please see [0045] of Chu which describes polystyrene or silicone latex beads.
Regarding claim 73, modified Chu teaches the cytometry system of Claim 56.
The positive microparticle complexes have not been positively recited as a part of the system, therefore the limitation “wherein the labeled detection reagent is a fluorescently labeled detection reagent.” is considered to be met.
However, please see Chu [0004] and [0005] which describes the fluorophore, which is the fluorescently labeled detection reagent.
Claim(s) 57, 79 is/are rejected under 35 U.S.C. 103 as being unpatentable over Chu (US-2006/0240444-A1) as evidenced by Ward (US-5627037-A), Beckman Coulter Cytomics FC 500 MPL flow cytometry system 2003, herein Beckman Coulter, and Mohapatra (US-2007/0036867-A1), and in further view of Mills (US-2006/0024744-A1) and as evidenced by abcam Data analysis in flow cytometry, herein abcam.
Regarding claim 57, modified Chu teaches the cytometry system of Claim 56. Chu further teaches wherein the labeled detection reagent is a fluorescently labeled detection reagent (Chu; [0004], [0005] see fluorophore), further, Chu describes where a histogram is obtained to display number of bead versus fluorescence intensity, and that gating is performed to isolate the beads depending on side scatter (SSC) determined by brightness of fluorescence and forward light scatter (FSC) determined by bead size (Chu; [0049]), however Chu does not teach wherein the non-transitory computer readable medium further comprises instructions that cause the processor to determine a mean or a median fluorescence intensity of the positive microparticle complexes acquired by the system,
thereby determining the level of the biomarker present in the cell-microparticle co-culture.
In the analogous art of quantitative and qualitative evaluation of biological samples, Mills teaches high through-put methods for monitoring treatment of patients being administered a soluble ligand that binds with a cell marker (Mills; [0001], [0013]).
Specifically, Mills teaches where a third fluorescent label is detected to monitor heparin therapy of a patient, where detecting the mean fluorescence intensity of the third fluorescent label bound to the capture particle assesses the amount of anti-heparin autoantibody in the blood of a patient (Mills; [0151]). [0148] of Mills describes detecting can be accomplished using an image processor or flow cytometer to determine relative intensities of two or more fluorescent labels.
It would have been obvious to one skilled in the art to modify the software of modified Chu such that it further measures mean fluorescence of the bead groups because it is taught by Mills that it is known in the art to be desirable to determine the amount of an analyte in a sample and that mean fluorescence intensity is an effective measurement that relates to the amount of analyte present in the sample (Mills; [0151]).
It is evidenced by abcam page 4/7 that the mean fluorescence intensity measures the brightness and is a relative measure of antigen abundance.
Regarding claim 79, modified Chu teaches the cytometry system of Claim 56.
Chu further teaches wherein the labeled detection reagent is a fluorescently labeled detection reagent (Chu; [0004], [0005] see fluorophore), further, Chu describes where a histogram is obtained to display number of bead versus fluorescence intensity, and that gating is performed to isolate the beads depending on side scatter (SSC) determined by brightness of fluorescence and forward light scatter (FSC) determined by bead size (Chu; [0049]), however Chu does not teach wherein the non-transitory computer readable medium further comprises instructions that cause the processor to determine a mean or a median fluorescence intensity of the positive microparticle complexes acquired by the system, wherein the mean or the median fluorescence intensity corresponds to the relative biomarker secreting capability of the responding cells.
In the analogous art of quantitative and qualitative evaluation of biological samples, Mills teaches high through-put methods for monitoring treatment of patients being administered a soluble ligand that binds with a cell marker (Mills; [0001], [0013]).
Specifically, Mills teaches where a third fluorescent label is detected to monitor heparin therapy of a patient, where detecting the mean fluorescence intensity of the third fluorescent label bound to the capture particle assesses the amount of anti-heparin autoantibody in the blood of a patient (Mills; [0151]). [0148] of Mills describes detecting can be accomplished using an image processor or flow cytometer to determine relative intensities of two or more fluorescent labels.
It would have been obvious to one skilled in the art to modify the software of modified Chu such that it further measures mean fluorescence of the bead groups because it is taught by Mills that it is known in the art to be desirable to determine the amount of an analyte in a sample and that mean fluorescence intensity is an effective measurement that relates to the amount of analyte present in the sample (Mills; [0151]).
It is evidenced by abcam page 4/7 that the mean fluorescence intensity measures the brightness and is a relative measure of antigen abundance.
The limitation “the mean or the median fluorescence intensity corresponds to the relative biomarker secreting capability of the responding cells.” is directed to the function of the apparatus and/or the manner of operating the apparatus, all the structural limitations of the claim has been disclosed by modified Chu and the apparatus of modified Chu is capable of determining the mean fluorescence of the positive microparticle complexes. As such, it is deemed that the claimed apparatus is not differentiated from the apparatus of modified Chu (see MPEP §2114).
In other words, the limitation “the mean or the median fluorescence intensity corresponds to the relative biomarker secreting capability of the responding cells.” is not a step being performed by the processor.
Claim(s) 59 is/are rejected under 35 U.S.C. 103 as being unpatentable over Chu (US-2006/0240444-A1) as evidenced by Ward (US-5627037-A), Beckman Coulter Cytomics FC 500 MPL flow cytometry system 2003, herein Beckman Coulter, and Mohapatra (US-2007/0036867-A1), and in further view of Hotson (US-2015/0118247-A1).
Regarding claim 59, modified Chu teaches the cytometry system of Claim 56. While Chu does teach a flow cytometry system (Chu; [0049]), Chu does not teach wherein the flow cytometry system is a mass cytometry system.
In the analogous art of obtaining from results of an assay comprising determining functional status of an immunomodulatory receptor (IMP), where the surface expression levels of the IMR can be determined, determination comprises cytometry such as flow or mass cytometry (Hotson; [0031]).
Specifically, Hotson teaches where any suitable method of evaluating single cells may be used, for example flow or mass cytometry (Hotson; [0115]). [0323] of Hotson describes that mass cytometry is different from flow cytometry in that the antibodies are tagged with mass labels rather than fluorescent labels and that detection is carried out by mass spectrometry, where mass cytometry presents the potential advantage of being capable of detecting a larger number of signals than flow cytometry.
It would have been obvious to one skilled in the art to modify the system of modified Chu such that it is a mass cytometry system because it is taught by Hotson that mass cytometry has the advantage of detecting a larger number of signals (Hotson; [0323]).
Examiner further finds that the prior art contained a device/method/product (i.e., a flow cytometry system) which differed from the claimed device by the substitution of component(s) (i.e., utilizing flow cytometry) with other component(s) (i.e., utilizing mass cytometry), and the substituted components and their functions were known in the art as above set forth. An ordinarily skilled artisan could have substituted one known element with another (i.e., flow cytometry for mass cytometry), and the results of the substitution (i.e., computing percentages of bead groups) would have been predictable.
Therefore, pursuant to MPEP §2143 (I), Examiner concludes that it would have been obvious to an ordinarily skilled artisan to substitute flow cytometry of reference Chu with mass cytometry of reference Hotson, since the result would have been predictable.
Claim(s) 75-76 is/are rejected under 35 U.S.C. 103 as being unpatentable over Chu (US-2006/0240444-A1) as evidenced by Ward (US-5627037-A), Beckman Coulter Cytomics FC 500 MPL flow cytometry system 2003, herein Beckman Coulter, and Mohapatra (US-2007/0036867-A1), and in further view of Hotson (US-2015/0118247-A1) as evidenced by CyTOF XT PRO.
Regarding claim 75, modified Chu teaches the flow cytometry system of Claim 56. While Chu does teach a flow cytometry system that uses fluorophores (Chu; [0049]), Chu does not teach wherein the labeled detection reagent is a detection reagent labeled with a metal element.
In the analogous art of obtaining from results of an assay comprising determining functional status of an immunomodulatory receptor (IMP), where the surface expression levels of the IMR can be determined, determination comprises cytometry such as flow or mass cytometry (Hotson; [0031]).
Specifically, Hotson teaches where any suitable method of evaluating single cells may be used, for example flow or mass cytometry (Hotson; [0115]). [0323] of Hotson describes that mass cytometry is different from flow cytometry in that the antibodies are tagged with mass labels rather than fluorescent labels and that detection is carried out by mass spectrometry, where mass cytometry presents the potential advantage of being capable of detecting a larger number of signals than flow cytometry. [0177] of Hotson describes that exemplary mass labels are those used for detection in the CyToF instruments.
It would have been obvious to one skilled in the art to modify the system of modified Chu such that it is a mass cytometry system because it is taught by Hotson that mass cytometry has the advantage of detecting a larger number of signals (Hotson; [0323]).
Examiner further finds that the prior art contained a device/method/product (i.e., a flow cytometry system) which differed from the claimed device by the substitution of component(s) (i.e., utilizing flow cytometry) with other component(s) (i.e., utilizing mass cytometry), and the substituted components and their functions were known in the art as above set forth. An ordinarily skilled artisan could have substituted one known element with another (i.e., flow cytometry for mass cytometry), and the results of the substitution (i.e., computing percentages of bead groups) would have been predictable.
Therefore, pursuant to MPEP §2143 (I), Examiner concludes that it would have been obvious to an ordinarily skilled artisan to substitute flow cytometry of reference Chu with mass cytometry of reference Hotson, since the result would have been predictable.
As evidenced by CyTOF XT PRO on page 5 of 8 the section titled “Technology” recites “Cytometry by time-of-flight or mass cytometry (on which CyTOF technology is based) is a proteomic technology that uses metal-conjugated antibody to simultaneously analyze 50-plus intracellular and surface markers in biological samples at single-cell resolution.” Therefore, the mass labels of Hotson are metal elements.
Regarding claim 76, modified Chu teaches the flow cytometry system of Claim 75. Chu has been modified by Hotsun to now be conducting mass cytometry, please see claim 75 supra.
Claim(s) 77 is/are rejected under 35 U.S.C. 103 as being unpatentable over Chu (US-2006/0240444-A1) as evidenced by Ward (US-5627037-A), Beckman Coulter Cytomics FC 500 MPL flow cytometry system 2003, herein Beckman Coulter, and Mohapatra (US-2007/0036867-A1), and in further view of Pahuski (US-5700645-A).
Regarding claim 77, modified Chu teaches the cytometry system of Claim 56. [0007] of Chu does describe that “a target molecule associated with a disorder” refers to any molecules produced by a disease process, where examples of a target molecule includes antigens expressed or secreted by pathogens or diseased cells. Chu does not teach wherein the non-transitory computer readable medium further comprises instructions that cause the processor to determine a number of cells in the cell-microparticle co-culture that were responsive to the stimulant based on the percentage of the positive microparticle complexes among the total number of microparticle complexes.
In the analogous art of cell analysis, Pahuski teaches where to measure or quantify the number of somatic cells in a milk sample, a cellular metabolite such as ATP is measured, and that the number of somatic cells present in the sample is calculated using the known amount of ATP that was measured and the average amount of ATP known to exist in somatic cells (Pahuski; abstract, column 11 lines 11-24).
It would have been obvious to one skilled in the art to modify the software of modified Chu such that it includes information on the target molecule of pathogens or diseased cells such as the average amount known to exist in these pathogens or cells and that the software calculates the number of cells present as taught by Pahuski because Pahuski teaches that it is desirable to quantify the number of cells in a sample and that knowing information on the cell, such as average amount of metabolite, is effective for calculating the number of cells present (Pahuski; column 11 lines 11-24).
Claim(s) 78 is/are rejected under 35 U.S.C. 103 as being unpatentable over Chu (US-2006/0240444-A1) as evidenced by Ward (US-5627037-A), Beckman Coulter Cytomics FC 500 MPL flow cytometry system 2003, herein Beckman Coulter, Mohapatra (US-2007/0036867-A1), and Pahuski (US-5700645-A), and in further view of Mills (US-2006/0024744-A1) and as evidenced by abcam Data analysis in flow cytometry, herein abcam.
Regarding claim 78, modified Chu teaches the cytometry system of Claim 77.
Chu further teaches wherein the labeled detection reagent is a fluorescently labeled detection reagent (Chu; [0004], [0005] see fluorophore), further, Chu describes where a histogram is obtained to display number of bead versus fluorescence intensity, and that gating is performed to isolate the beads depending on side scatter (SSC) determined by brightness of fluorescence and forward light scatter (FSC) determined by bead size (Chu; [0049]), however Chu does not teach wherein the non-transitory computer readable medium further comprises instructions that cause the processor to determine a mean or a median fluorescence intensity of the positive microparticle complexes acquired by the system, wherein the mean or the median fluorescence intensity corresponds to the relative biomarker secreting capability of the responding cells.
In the analogous art of quantitative and qualitative evaluation of biological samples, Mills teaches high through-put methods for monitoring treatment of patients being administered a soluble ligand that binds with a cell marker (Mills; [0001], [0013]).
Specifically, Mills teaches where a third fluorescent label is detected to monitor heparin therapy of a patient, where detecting the mean fluorescence intensity of the third fluorescent label bound to the capture particle assesses the amount of anti-heparin autoantibody in the blood of a patient (Mills; [0151]). [0148] of Mills describes detecting can be accomplished using an image processor or flow cytometer to determine relative intensities of two or more fluorescent labels.
It would have been obvious to one skilled in the art to modify the software of modified Chu such that it further measures mean fluorescence of the bead groups because it is taught by Mills that it is known in the art to be desirable to determine the amount of an analyte in a sample and that mean fluorescence intensity is an effective measurement that relates to the amount of analyte present in the sample (Mills; [0151]).
It is evidenced by abcam page 4/7 that the mean fluorescence intensity measures the brightness and is a relative measure of antigen abundance.
The limitation “wherein the mean or the median fluorescence intensity corresponds to the relative biomarker secreting capability of the responding cells.” is directed to the function of the apparatus and/or the manner of operating the apparatus, all the structural limitations of the claim has been disclosed by modified Chu and the apparatus of modified Chu is capable of determining the mean fluorescence of the positive microparticle complexes. As such, it is deemed that the claimed apparatus is not differentiated from the apparatus of modified Chu (see MPEP §2114).
In other words, the limitation “wherein the mean or the median fluorescence intensity corresponds to the relative biomarker secreting capability of the responding cells.” is not a step being performed by the processor.
Allowable Subject Matter
Claims 80-83 would be allowable if rewritten or amended to overcome the rejection(s) under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action.
The following is a statement of reasons for the indication of allowable subject matter:
Regarding claim 80, the closest prior art of record is Chu (US-2006/0240444-A1) as evidenced by Ward (US-5627037-A), Beckman Coulter Cytomics FC 500 MPL flow cytometry system 2003, herein Beckman Coulter, and Mohapatra (US-2007/0036867-A1).
While Chu does describe in [0007] that the target molecules include antigens expressed by or secreted by pathogens or diseased cells, and [0033] describes that to detect the target molecule involves mixing and incubating coated beads and detection antibody with a sample suspected of containing the target molecule, the mixing and incubating is not a co-culture.
Page 8 lines 19-20 of the instant specification recites “By “co-culturing” is meant that the cells are cultured (e.g., grown/maintained under controlled conditions) in the presence of the microparticles.” The beads and sample of Chu are only mixed and incubated, where there is no indication that the sample is grown or maintained during this process.
Translated Lin (CN-101762703-A), newly of record, does teach where a mixture of microsphere carriers of different diameters and different built-in fluorescence is co-cultured with serum and other samples in the same test tube (Lin; [0018]). However, serum is understood to not include cells and therefore Lin does not teach a “cell-microparticle co-culture”.
Claims 81-83 are dependent on claim 80 and would be allowable by virtue of being dependent on an allowable claim, however please note that there are 112 issues that need to be addressed.
Response to Arguments
Applicant’s arguments, see page 9, filed 04/20/2026, with respect to the rejection(s) of claim(s) 56-59, 69-76 under 35 USC 103 have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Chu (US-2006/0240444-A1) as evidenced by Ward (US-5627037-A), Beckman Coulter Cytomics FC 500 MPL flow cytometry system 2003, herein Beckman Coulter, and Mohapatra (US-2007/0036867-A1).
Conclusion
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Curtis Mayes can be reached at (571)272-1234. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/S.Y.L./Examiner, Art Unit 1796
/MELVIN C. MAYES/Supervisory Patent Examiner, Art Unit
Prosecution Insights