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 Amendment
Applicant amendments filed 11/24/2025 have been entered. Applicant amendments overcomes the previous claim objection, 112(a) rejections set forth in the Office Action mailed 09/11/2025, the previous claim objection and 112(a) rejections are withdrawn. Applicant amendments do not overcome each and every 112(b) rejection set forth in the Office Action mailed 09/11/2025, please see 112 section below.
Status of Claims
Claims 56-59 and 69-76 remain pending in the application.
Claim Objections
Applicant is advised that should claim 57 be found allowable, claim 74 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
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 and 69-76 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 recites “wherein each positive microparticle complex comprises a microparticle complex that further comprises a secreted biomarker bound to the capture ligand,” on lines 10-11 where it is unclear if the microparticle complex of the positive microparticle complex is the same or different from the microparticle complex described on line 9.
For examination, it will be interpreted that they are the same microparticle complex.
It is suggested to amend lines 10-11 to recite “wherein each positive microparticle complex comprises [[a]] the microparticle complex that further comprises a secreted biomarker bound to the capture ligand”
Claims 57-59 and 69-76 are rejected by virtue of being dependent on a rejected claim.
Claim 58 recites “wherein the flow cytometry system is a flow cytometry system” on lines 1-2, where it is unclear what the system is. If the system of claim 56 is already a flow cytometry system, see line 1, then is the flow cytometry system of claim 58 different?
For examination, it will be interpreted that if the system is a flow cytometry system, it will meet the limitations of claim 58.
Claim 59 recites “wherein the flow cytometry system is a mass cytometry system.” on lines 1-2, where it is unclear how a flow cytometry system is now a mass cytometry system as a mass cytometry system is understood to not be a more specific type of flow cytometry system. Rather, mass cytometry and flow cytometry are two different systems that use different labels.
Claim 75 recites “wherein the labeled detection reagent is a detection reagent labeled with a metal element.” on lines 1-2, where it is unclear how a flow cytometry system will now have a metal element, as a metal element is understood to be for mass cytometry (see instant specification page 18 lines 13-16 which supports this as metal elements are used in mass cytometry). Is it still a flow cytometer if metal elements are being used?
Claim 76 is rejected by virtue of being dependent on a rejected claim.
Claim 76 recites “wherein the system is a mass cytometry system.” on lines 1-2, where similar for reasons described in claim 59, it is unclear how a flow cytometry system is now a mass cytometry system as they are understood to be two different things.
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) in view of Beckman Coulter Cytomics FC 500 MPL flow cytometry system 2003, herein Beckman Coulter.
Regarding claim 56, Chu teaches a flow 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 flow cytometry system (Beckman Coulter Cytomics FC 500 MPL Flow Cytometry System) to identify a total number of microparticle complexes from a cell-microparticle co-culture and identify a total number of positive microparticle complexes from the cell-microparticle co-culture ([0004] see detecting a target molecule in a test sample that uses a plurality of beads that are coated with an antibody that specifically binds to a first epitope of a target molecule and a detection antibody that specifically binds to a second epitope of the target molecule that is labeled with a fluorophore, [0049] see fluorophore-labeled beads upon excitement by a laser fluoresces and a histogram is obtained to display the number of beads versus fluorescence intensity, where gating is then performed to isolate electronically the special group of beads of the same size depending on side scatter (SSC) determined by brightness of fluorescence and forward light scatter (FSC) determined by bead size, [0050] see contourgram is also obtained that allows one to compute the percentage of bead groups as determined by two fluorescences and two sizes where the percentage of each bead subpopulation can be determined),
calculate the percentage of the positive microparticle complexes among the total number of microparticle complexes ([0049] and [0050] where by calculating the percentage of each bead subpopulation, a specific subpopulation that is being focused on is considered the positive microparticle complex).
Please note that the cell-microparticle co-culture has not been positively recited in the claim, and therefore it is not a part of the claimed flow cytometry system. Therefore, the limitation “direct the flow cytometry system to identify a total number of microparticle complexes 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.
Additionally, 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 a microparticle and a capture ligand,
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,
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; and
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.
Regarding claim 58, modified Chu teaches the flow cytometry system of Claim 56. Chu further teaches wherein the flow cytometry system is a flow cytometry system
Regarding claim 69, modified Chu teaches the flow 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 flow 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 flow 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 flow 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 flow 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, 74 is/are rejected under 35 U.S.C. 103 as being unpatentable over Chu (US-2006/0240444-A1) and Beckman Coulter Cytomics FC 500 MPL flow cytometry system 2003, herein Beckman Coulter, 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 flow cytometry system of Claim 56. Chu does teach 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 74, modified Chu teaches the flow cytometry system of Claim 56. Chu does teach 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 labeled detection reagent is a fluorescently labeled detection reagent, and 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.
Claim(s) 59 is/are rejected under 35 U.S.C. 103 as being unpatentable over Chu (US-2006/0240444-A1) and Beckman Coulter Cytomics FC 500 MPL flow cytometry system 2003, herein Beckman Coulter, and in further view of Hotson (US-2015/0118247-A1).
Regarding claim 59, modified Chu teaches the flow 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) and Beckman Coulter Cytomics FC 500 MPL flow cytometry system 2003, herein Beckman Coulter, 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.
Response to Arguments
Applicant arguments and amendments filed 11/24/2025 with regards to 112(a) rejections have been fully considered and are persuasive, therefore the 112(a) rejections are withdrawn. Applicant arguments and amendments are not persuasive to overcome all of the previous 112(b) rejections set forth in the Office Action mailed 09/11/2025, please see above.
Due to amendments filed 11/24/2025, the rejections set forth in the Office Action dated 09/11/2025 are withdrawn. However, in light of a new search for the newly presented amendments, a new rejection is set forth above.
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.
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/S.Y.L./Examiner, Art Unit 1796
/ELIZABETH A ROBINSON/Supervisory Patent Examiner, Art Unit 1796
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