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. 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. Election/Restrictions Applicant's election with traverse of Group II, claims 16-25, in the reply filed on 03/06/2026 is acknowledged. The traversal is on the ground(s) that the groups of invention have been mischaracterized, for example, at remarks page 9 Applicant asserts that Groups II and I are not combination/subcombination, but rather are directed to distinct methods applicant arguing Group I is directed to a method of analyzing particles in a sample using a surface area probe or volume probe, and Group II is directed to a method of identifying and/or quantifying a particle of interest in a sample using a molecular marker-specific probe. A pplicant is arguing that the claimed Groups I and II are still distinct methods, although for different reasons as indicated in the Restriction Requirement ( and as such would still be subject to Restriction ), however, upon further consideration by the present Examiner, the claims of indicated Groups I and II are considered to have substantial overlap. As a result, a search of the prior art has been extended and claims 2-15 are examined presently with the claims of Group II (i.e., the claims of Group I and II are examined presently). Regarding the inventions of claims 23-28, Applicant argues that Groups III and IV are not combination/ sub combination claims, but rather distinct methods (see at remarks page 9, Applicant refers to the groups of invention as distinct methods, however it appears this is typographical error and that Applicant intended to argue are distinct products since these claims are not method claims ). The Examiner agrees with Applicant’s remarks that the inventions of these Groups are distinct (distinct product invention) : The inventions are independent or distinct, each from the other because: Inventions of Groups III (claims 23-25) and IV (claims 26-28) are directed to related products . The related inventions are distinct if: (1) the inventions as claimed are either not capable of use together or can have a materially different design, mode of operation, function, or effect; (2) the inventions do not overlap in scope, i.e., are mutually exclusive; and (3) the inventions as claimed are not obvious variants. See MPEP § 806.05(j). In the instant case, the inventions as claimed satisfy all 3 requirements, the claimed inventions of these groups have materially different design, mode of operation and function, consistent with Applicant’s arguments these are distinct products in that they include structurally different probes, one target surface membranes (surface area probe/volume probe), the other targeting a particular molecular species on a membrane (protein/targeted antigen) . These Groups of invention differ in scope are compositionally distinct in that they are not obvious variants of one another (one could not be used in place of the other for its same purpose) Furthermore, the inventions as claimed do not encompass overlapping subject matter and there is nothing of record to show them to be obvious variants. Regarding remarks specific to the restriction requirement between the method and product claims (remarks page 10), Applicant arguments support the restriction (arguing the method claims of Group I are not limited to the optical standard particles of Group III or Group IV, further that Group II recite generic use of a preparation of particles, these arguments do not persuasively make the case that there is no burden in examining the claims together, rather these arguments appear to support that the Groups are separate/distinct inventions. The requirement is still deemed proper and is therefore made FINAL. Claims 23-28 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected Groups of invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 03/06/2026. Claims 2-9, 15-22 and 29-33 are examined below . Priority The present application is a Continuation of application serial 16/534,854, filed 08/07/2019 (US Patent 11,486,854), which is a Divisional of 15/233,723, filed 08/10/2016 (US Patent 10,429,302). Application 15/233,723 claims benefit under 35 U.S.C. 119(e) to provisional application No. 62/203,594 , filed 08/11/2015 . Information Disclosure Statement The information disclosure statement (IDS) entered 08/27/2025 has been considered, initialed and is attached hereto. Claim Objections Claim s 2, 6 , 19 and 21 are objected to because of the following informalities: Claim 2 is objected to for a typographical error, at claim 2, step (b), “in(a)” is missing a space and appears as though it should read: “in (a)”. Claims 6, 19 and 21 each recite abbreviations in the claims (e.g., di-8- ANEPPS, di-4-ANEPPS, F2N12S, FM-143, PKH dye, anti-EGFRvIII, anti-EGFR, anti-GLAST, FITC, PE-Cy5.5, PE-Cy7, APC, APC-Alex647, APC-Alexa700, APC-Alex750). It is suggested at the first instance of every abbreviation, that the abbreviation accompany its full meaning in order to improve clarity of the record. Appropriate correction is required. 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 appl icant regards as his invention. Claim s 2-9, 15-22 and 29-33 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. Claims 2 , 15 and 29 each recite the limitation “surface area probe or volume probe interacts with the particles stoichiometrically with respect to surface to particle surface area or volume”, regarding the terminology “interacts stoichiometrically”, the originally filed specification refers to this language in to different contexts, namely as indicated in the present claims in relation to the surface area probe or volume probe, and in relation to optically detectable label comprising a molecular-specific probe (as recited at, for example claim 16). Regarding this language related to surface area probe or volume probe, this language is indefinite because it unclear how a “surface area probe” or a “volume probe” can be determined to interact “stoichiometrically” given that the meaning of stoichiometric appears generally to mean a quantitative relationship between constituents. Considering that a membrane, lipid layer is a continuous structure, it is not clear how each dye/probe molecule could or would interact in a quantitative way that could be considered “stoichiometric” as claimed (unlike in relation to molecular specific probe where each binding partner binds a targeted antigen/protein at a membrane surface). Further claims 2-6, 15, 17 and 29, regarding the claimed language “surface area probe” and “volume probe”, the specification fails to provide a specific or limiting definition for this language, and there is no art recognized definition or understanding for what is and is not considered to be a “surface area probe” or a “volume probe” relative to particles such as those claimed. Although the claims recite “surface area probe” and “volume probe” in the alternative (using the language “or”), the originally filed specification at page 8 indicates examples of species that can be considered such probes, and indicates “In some aspects, the surface area probe or volume probe intercalates into the bilayer membrane”. However, t he recited language is indefinite for two reasons, 1. the claim recites these two terminologies as distinct species by using the language “or” between them in the claim, where as the specification contradicts this language and suggests that a surface area probe and volume probe are one in the same, and 2. the boundaries of what is and is not encompassed by this language is unclear in that, other than the particular examples which are recited as membrane intercalating dye examples recited in the originally filed specification (such as: di-8- ANEPPS, di-4-ANEPPS, F2N12S, FM-143, Cell Mask Orange, Cell Mask Green, Cell Mask Deep Red, a carbocyanine dye or a PKH dye ), it is not readily clear what other “probes” are encompassed or excluded by the recited language. In particular, the claims are not limited to those examples, and it is not clear what other species/type of probes would read on the claimed “surface area probe” or “volume probe” beyond those limited species. The above rejection is further supported by the language at claim 17, “determining the surface area or volume of the particle based on the detected optical signal of the surface probe or volume probe, respectively”, this language (“respectively”) further suggests that surface area probe and volume probe are distinct species of probe , providing distinct information , which is contradictory to the cited portion of the originally filed specification indicated above. Claim 21 contain s trademarks/tradenames, namely, “ Dylight ” , “Pacific Blue”, “Brilliant Blue”, “Cy”, “Chrome Orange” (further it is unclear if Applicant meant “Krome Orange”, which is an fluorescent dye trademarked by Beckman Coulter, in reference to a particular specialized fluorescent dye used in flow cytometry) . Where a trademark or tradename is used in a claim as a limitation to identify or describe a particular material or product, the claims does not comply with the requirements of 35 U.S.C. 112(b). See Ex parte Simpson , 218 USPQ1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or tradename cannot be used to properly identify any particular material or product. A trademark or tradename is used to identify a source of goods, and not the good themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, each is relied upon to indicate a specific/particular fluorescent probe species. Claim Rejections - 35 USC § 103 The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action: A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made. Claim (s) 16 , 18 , 20 -22 are rejected under 35 U.S.C. 103 as being unpatentable over Lambert et al., US PG Pub No. 2007/0111225A1 in view of Maher et al., Quantitative flow cytometry in the clinical laboratory, Clinical and Applied Immunology Reviews, 5(6), (2005), p. 353-372, and Thill, AU2003/243273 A1 (English Machine Translation obtained via Espacenet attached) . Lambert et al. teach a method of identifying a particle of interest (e.g., a cell), the method comprising contacting the particle of interest with an optically detectable label comprising a molecule specific probe (see e.g., para [0057], fluorophore conjugated probes that selectively bind an analyte), the optically detectable label of Lambert et al. interacts with a molecular marker associated with the particle of interest. Lambert’s method comprises detecting the particle of interest-associated optically detectable label to obtain an optical signal intensity (para [0057], a preparation of particles, i.e., target cells, are contacted with the optically detectable label, i.e., the fluorophore conjugated probes and allowed to interact such to associate and complex is obtained, see obtaining optical signal intensities corresponding to the particle-associated optically detectable labels, i.e., formed complexes). Lambert et al. addresses claim 16, step (c), (iv) because Lambert et al. teach detected signal correlates with an identity (see para [0057], the detected signal identifies the type of probe (see also described at para [0068], using several color labels achieves spectral barcoding for multiplex detection) . Lambert’s method is, based on a predetermined correlation between the identity of the fluorophore label, and the optical signal intensity observed, identifying a particle of interest. (See also Lambert at abstract, claims, e.g., claims 8-13, and also paras [0015]-[0017], [0022]-[0024]). Lamber t et al. teach targeted microorganisms or a cell (para [0024]), consistent with a bove teach detecting analytes such as protein (claim 18) , peptides or nucleic acids within cells (paras [0048], surface markers, proteins, nucleic acids, and [0054]), see also teach their method applicable to types of targeted particles including viruses (viral particle, see paras [0052] and [0077]). Lambert et al. teach merely detecting presence , and as such fails to clearly teach quantitative detection; further Lambert fails to specifically teach that the optically detectable label interacts stoichiometrically with each of the particles of the preparation, that the optical signal from each particle-associated optically detectable label is proportional to the number of molecules of the molecular marker on the corresponding particle with which the optically detectable label is associated. Maher et al. teach, regarding flow cytometry, that it has long been recognized that the intensity of the fluorescent signal is proportional to the amount of antibody bound per cell and therefore related to the number of antigen sites expressed (see abstract), that this relationship makes flow cytometers capable of quantifying antigen expression in terms of molecules per cell. Maher et al. (abstract) teach that advances over time have resulted in the development of flow cytometric methods and materials that permit one to conduct measures of quantitative fluorescence with improved levels of control and interlaboratory precision, that such advances are of interest for quantifying expression and activities of a variety of proteins and enzymes for diagnostic, prognostic and therapeutic purposes. See further, page 354, para 1, Maher teach quantitative flow cytometry, quantifying the number of bound molecules, allows one to make inferences about the cellular concentration of the target antigen, that this information in the context of phenotypically defined subsets, is proving to be a powerful technique with predicted far reaching applications through biology. At pages 359-361 Maher et al. discuss the clinical utility of such quantitate detection, demonstrating that quantitative flow cytometry has a greater diagnostic sensitivity to detect quantitative deficiencies compared to conventional flow cytometric methods (see further pages 361-362, Maher provide examples to demonstrate the value of quantitative flow cytometry). Thill teach (see at page 13, last paragraph of the document obtained via Espacenet) that flow cytometers typically use lasers and measure light scattered by cells to provide information about size and internal structure, and that these systems use fluorescence in several spectral regions emitted by labeled probes that bind specifically and stoichiometrically to cellular constituents such as antigens. It would have been prima facie obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have modified the methods of Lambert et al. in order to perform quantitative flow cytometry (i.e., to have modified the method such that instead of merely detecting presence, the flow cytometry method is performed as quantitative flow cytometry) , one motivated to make the modification because quantitative flow cytometry was recognized as an advancement to the technique (Maher et al., the modification would allow one to obtain measures of quantitative fluorescence with improved levels of control and interlaboratory precision, that such advances are of interest for quantifying expression and activities of a variety of proteins and enzymes for diagnostic, prognostic and therapeutic purposes) . Given the art recognized advantages afforded by quantitative flow cytometry, it would have been obvious to have modified Lambert’s method for detecting presence in order to be a quantitative form of the technique in order to achieve the same improved level of detection. One having ordinary skill in the art would have a reasonable expectation of success because Maher teach that, regarding flow cytometry, it has long been recognized that the intensity of the fluorescent signal is proportional to the amount of antibody bound per cell and therefore related to the number of antigen sites expressed (see abstract), that this relationship makes flow cytometers capable of quantifying antigen expression in terms of molecules per cell. Further one having ordinary skill would have a reasonable expectation of success because Lambert’s method is a method of flow cytometry. Further, it would have been prima facie obvious to one having ordinary skill before the effective filing date of the claimed invention when performing the quantitative flow cytometry method as taught by the cited prior art, that the labeled binding particle (the optically detectable label ) interacts stoichiometrically with each of the cells (target particles of the preparation ) , further that the optical signal from each particle-associated optically detectable label is proportional to the number of molecules of the molecular marker on the corresponding particle with which the optically detectable label is associated because the prior art recognized that these systems use fluorescence in several spectral regions emitted by labeled probes that bind specifically and stoichiometrically to cellular constituents such as antigens (Thill), further one would expect success given that the prior art acknowledged that it has long been recognized that the intensity of the fluorescent signal is proportional to the amount of antibody bound per cell and therefore related to the number of antigen sites expressed (Maher et al.). Regarding claim 20, see as cited in detail above, the combination of the cited art teach an optically detectable label that is a fluorophore. Regarding claim 21, Lambert teach suitable fluorescent labels (fluorophore) including FITC (para [0061] ). Regarding claim 22, see as cited above, the combination of the cited art encompasses marker specific probe that is a protein (antibody), label that is a fluorophore, and the probe is conjugated to the fluorophore. Claim(s) 17 - 22 and 29- 33 are rejected under 35 U.S.C. 103 as being unpatentable over Lamber et al. in view of Maher et al. and Thill et al., as applied to claim 16 above, and further in view of Schettini et al., WO2014/082083 and Horman et al . , US PG Pub No. 2014/0309171A1. Lambert et al. in view of the cited prior art teach a method substantially as claimed (see above); however, fails to teach further contacting the particle of interest with one or more optically detectable labels comprising a surface area probe or a volume probe (see originally filed specification, the terminology “surface area probe” appears to include, for example cell membrane type dyes, for example di-8-ANEPPS, an art recognized cell membrane permeability dye referenced as an example of a “surface area probe”, page 34 of the originally filed specification). Because Lambert fails to teach the claimed dual staining, Lambert fail to teach detecting the optical signal of the particle associated optically detectable labels comprising the surface area probe without physical separation or isolation of the particle of interest, determining the surface area or volume of interest based on the detected optical signal, and determining size of the particle based on the determined surface area. Schettini et al. teach ( abstract ) assessing microvesicles in a biological sample, detecting circulating biomarkers for profiling, physiological states or phenotyping (abstract ). Schettini et al. teach circulating biomarkers can be associated with circulating vesicles, i.e., membrane encapsulated structures shed from cells found in bodily fluids, which can be analyzed for associated diseases (para [0007]), para [0008], Schettini teaching these structures provide a source of biomarkers, useful for diagnostic, prognostic and theranostic readout (see para [0008], teaching characteristics such as size , surface antigens, cell origin and payload as contributing to providing diagnostic, prognostic and theranostic readout) . See para [0009], Schettini teach characterizing phenotype by detection biomarkers indicative of disease and disease progression. At para [001273], Schettini et al. teach as an example, using a dual staining technique, namely comprising antibodies to circulating microvesicle proteins and lipid intercalating dyes , performed in order to identify and separate circulating microvesicles from biological debris using flow cytometry. See at para [001274], Schettini teach lipid bi-layer intercalating dyes identify particles that contain lipid membranes, that since lipid dyes may also bind membrane fragments, staining for proteins known to be associated with cell plasma membranes are also included, including CD9, CD63 and CD81. At para [00231] Schettini teach, regarding flow cytometry, that this technique allows simultaneous multiparametric analysis of the physical and/or chemical characteristics of single cells flowing through a detection apparatus, that forward scatter correlates with cell size , and side scatter depends factors such as shape of nucleus, etc. Horman et al. teach (para [0144]) that flow cytometry is advantageous because it allows for rapid, quantitative, single cell analysis, that proteins can be detected in a specific cell type within a heterogenous population via cell surface marker phenotyping without the need to physically separate the cells. It would have been prima facie obvious to one having ordinary skill in the art to have modified the quantitative method (for detecting cells via cell surface antigen) as taught by the combination of Lambert et al., Maher and Thill, in order to target circulating microvesicles for diagnostic, prognostic and theranostic use (see Schettini, cited above, circulating microvesicles a source of disease specific diagnostic markers in bodily fluid samples), the modification a simple substitution of one art recognized target for another, both cells and circulating microvesicles recognized in the prior art as exhibiting detectable antigenic markers, both further known detectable using flow cytometry, one motivated to target circulating microvesicles for the purposes of diagnosis/prognosis of disease. One having ordinary skill in the art would have a reasonable expectation of success because both are considered valuable targeted species (cells or microvesicles released from cells), and because the art teach like cells, microvesicles are detectable with techniques such as flow cytometry. Further in detection of microvesicles, it would have been prima facie obvious to have modified the method of Lambert to further contact the microvesicles particles with an optically detectable label comprising the surface area probe (a lipid intercalating dye, as in Schettini) because this technique would allow one to identify and separate circulating microvesicles from biological debris in the flow cytometry method (Schettini). Further, it would have been prima facie obvious , based on the further citation Schettini, to have performed forward and side scattering detection techniques, as referenced in Schettini, in order to determine the surface area of the particles, because Schettini teach size as a characteristic of interest with regard to the use of these particles for diagnostic/prognostic purposes, Schettini teaching forward scatter and side scatter provide information regarding size and shape, which one having ordinary skill in the art would expect to be valuable in techniques directed at discriminating debris from payload (antigen) carrying microvesicles in circulation. Regarding the claimed limitation “without physical separation or isolation of the particle of interest”, it would have been further prima facie obvious to one having ordinary skill performing the quantitative flow cytometry methods of the combination of the cited art to have performed the method in a heterogenous sample (i.e., to have performed flow cytometry without a step of separation or isolation of the particle of interest) because flow cytometry is a technique considered advantageous because it is a technique that accommodates rapid, quantitative, single cell analysis, detecting proteins in a specific cell type within a heterogenous population via cell surface marker phenotyping without the need to physically separate the cells (Horman). Omitting such a step, based on the cited art, is considered an advantageous feature of performing this technique for analysis, as a result the ordinarily skilled artisan would have a reasonable expectation of success not first isolating or separating, rather preforming detection in a heterogeneous sample, particularly since the combination of dual stains (membrane intercalating and antigen specific antibody probe) would be considered capable of distinguishing debris from targeted particles. Regarding claims 18-19, see as cited in detail above, Schettini (para [001274]) teach lipid bi-layer intercalating dyes identify particles that contain lipid membranes, that since lipid dyes may also bind membrane fragments, staining for proteins known to be associated with cell plasma membranes are also included, including CD9, CD63 and CD81. Regarding claim 20, see as cited in detail above, the combination of the cited art teach an optically detectable label that is a fluorophore. Regarding claim 21, Lambert teach suitable fluorescent labels (fluorophore) including FITC (para [0061]). Regarding claim 22, see as cited above, the combination of the cited art encompasses marker specific probe that is a protein (antibody), label that is a fluorophore, and the probe is conjugated to the fluorophore. Regarding claim 29, the combination of the cited prior art above is addresses samples comprising at least two particle species (i.e., heterogeneous samples, see as cited above, the combination of the cited art teaching detection in samples that are heterogeneous samples, not previously isolated particles), see as cited above, the method comprising contacting with surface area probe as claimed and molecular marker specific probe as claimed (dual labeling) . Regarding claims 30 and 31, see as cited above, the method comprising fluorescent label for both probe (fluorescent intercalating membrane dye, fluorescent labeled antibodies). Regarding claims 32-33, the combination of Lambert et al. and the cited prior art, particularly in view of Schnetti, as set forth above, addresses samples comprising microvesicles (particles) from a cell, detected in a biological fluid sample, particularly from a subject having cancer , the method using the dual labeling to detect both size and identity of the particles (see Schnetti et al. at para [00140], teaching vesicles assessed for surface antigens indicative of colorectal origin and the presence of cancer) . Claim (s) 2-9 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over WO2014/082083 in view of Horman et al . , US PG Pub No. 2014/0309171A1. Schettini et al. teach (paras [001271]-[001274]) a method of analyzing particles (circulating microvesicles) in a sample (biofluids) , the method comprising:(a) contacting a sample comprising the particles with one or more optically detectable labels, thereby forming a staining solution (see dual staining with antibodies to cMV proteins and lipid-intercalating dyes to detect membranes, para [001273]) , wherein (i) the particles comprise extracellular vesicles (EVs) , and (ii) the one or more optically detectable labels comprise a surface area probe (see originally filed specification, the terminology “surface area probe” appears to include, for example cell membrane type dyes, for example di-8-ANEPPS, an art recognized cell membrane permeability dye referenced as an example of a “surface area probe”, page 34 of the originally filed specification). Regarding the limitation, wherein the surface area probe or volume probe interacts with the particles stoichiometrically with respect to particle surface area or volume , see the rejection under 35 U.S.C. 112(b), it is unclear how a “surface area” probe interacts with particles “stoichiometrically”, however the prior art is teaching forming particles comprising particle-associated surface area probe , and it would be expected that the dye produce optical signal from intercalating with the membrane, thereby resulting in signal that is proportional to the surface area (the area encompassed by the membrane). Schnetti et al. does not teach the method performed without physical separation or isolation of the particles, detecting the optical signal of the one or more particle-associated optically detectable labels generated in(a), thereby analyzing the particles in the sample. Horman et al. teach (para [0144]) that flow cytometry is advantageous because it allows for rapid, quantitative, single cell analysis, that proteins can be detected in a specific cell type within a heterogenous population via cell surface marker phenotyping without the need to physically separate the cells. Regarding the claimed limitation “without physical separation or isolation of the particle of interest”, it would have prima facie obvious to one having ordinary skill in the art performing flow cytometry methods to have performed the method in a heterogenous sample (i.e., to have performed flow cytometry without a step of separation or isolation of the particle of interest) because flow cytometry is a technique considered advantageous because it is a technique that accommodates rapid, quantitative, single cell analysis, detecting proteins in a specific cell type within a heterogenous population via cell surface marker phenotyping without the need to physically separate the cells (Horman). Omitting such a step, based on the cited art, is considered an advantageous feature of performing this technique for analysis, as a result the ordinarily skilled artisan would have a reasonable expectation of success not first performing a step of isolating or separating, rather preforming detection in a heterogeneous sample, particularly since the combination of dual stains (membrane intercalating and antigen specific antibody probe) would be considered capable of distinguishing debris from targeted particles. Regarding claims 3 and 4, also noted, at para [00231] Schettini teach, regarding flow cytometry, that this technique allows simultaneous multiparametric analysis of the physical and/or chemical characteristics of single cells flowing through a detection apparatus, that forward scatter correlates with cell size , and side scatter depends factors such as shape of nucleus, etc. At the cited example of Schnetti (Example 47 starting at para [001271]), Schnetti does teach setting a flow cytometer to analyzer particles above a certain size, thereby suggesting Schnetti’s method involves size consideration. Also Schnetti does not clearly teach detecting the optical signal and determining the surface area of the particle based on the signal, it would have been further prima facie obvious, based on the further citation Schettini, to have performed forward and side scattering detection techniques, as referenced in Schettini, in order to determine the surface area of the particles in order to estimate their size because Schettini teach size as a characteristic of interest with regard to the use of these particles for diagnostic/prognostic purposes, Schettini teaching forward scatter and side scatter provide information regarding size and shape, which one having ordinary skill in the art would expect to be valuable in techniques directed at discriminating debris from payload (antigen) carrying microvesicles in circulation. Regarding claim 5, see para [001274] Schnetti is teaching fluorescent probes (fluorescent dyes). Regarding claim 6, Schnetti teach examples of carbocyanine dyes as suitable examples of lipid staining dyes (membrane intercalating dyes), see for example paras [0015], [00554] and [001274]. Regarding claim 7, Schnetti et al. teach examples of suitable dyes for associating with vesicle membrane, including CFSE (para [00554]. Although Schnetti does not refer to this dye as a “volume probe”, based on Applicant’s claims and originally filed specification, Schnetti, using this dye to evaluate whole microvesicles from debris, appears to be using the dye in the same manner consistent with the claims. Further, see MPEP 2112.01, "Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. a chemical composition and its properties are inseparable; in the present case, it appears that the prior art encompasses the same probe as claimed, used on the same type of target (microvesicles) to interrogate membrane. Regarding claim 8, see Schnetti teaching flow cytometry. Regarding claim 9, see the combination of the cited provides motivation to exclude a physical separation/isolation step. Regarding claim 15, see the combination of the cited art discussed in detail above addresses the claim, the combination of the cited art does address analyzing by determining size of the particles, see Schnetti does obtain predetermine correlation (compares to a predetermined size, Schnetti teach analyzing cells above a “certain size” the analyzer set to distinguish (para [001271]). As cited above, Schnetti does teach methods comprising particles contacted with the optically detectable label, resulting particles comprising the label obtained, correlating obtained signal with the set size). Double Patenting The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg , 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman , 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi , 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum , 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel , 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington , 418 F.2d 528, 163 USPQ 644 (CCPA 1969). A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b). The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13. The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA/25, or PTO/AIA/26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer . Claims 2 -5, 8-9, 15-16, 20 and 22 , rejected on the ground of nonstatutory double patenting a s being unpatentable over claims 1-11 of U.S. Patent No. U.S. Patent No. 10,429,302 (previously application 15/233,723) . Although the claims at issue are not identical, they are not patentably distinct from each other because : See ‘302 at claim 1, the claim is identical in scope to present claim 2, ‘302 claim 1 recites a method of analyzing particles in a sample, the methods comprising: (a) contacting a sample comprising the particles with one or more detectable labels, thereby forming a staining solution wherein the one or more optically detectable labels comprise a surface area probe or volume probe that interacts with the surface area or volume, respectively, thereby forming particles comprising particle-associated surface area probe or particle-associated volume probe, wherein the optical signal is proportional to the surface area or volume, respectively, of the particle. See ‘302 at claim 8, ‘302 recites that the particle is a liposome, vesicle, extracellular vesicle. Regarding claim 3, see ‘302 claim 3, determining surface area or volume. Regarding claim 4, see ‘302 claim 4, further comprising determining size. Regarding claim 5, see ‘302 claim 5, fluorescent probe. Regarding claim 8, see ‘302 claim 9, fluorescence spectroscopy, fluorescence imaging or flow cytometry. Regarding claim 9, see ‘302 claim 10, without separation, wherein separation or isolation comprises washing, or claim 10, centrifugation or ultracentrifugation. Regarding claim 15, ‘302 see claim 12, determining signal, obtaining predetermined, correlation, determining the size. Regarding claim 16, see ‘302 c laim 15, a method of identifying and/or quantifying a nanoparticle of interest as claimed, comprising the same steps (a) contacting, (b) detecting, (c) obtaining a predetermined correlation, (c) comprising steps (i)-(iv) as claimed, (d) identifying and/or quantifying based on the predetermined correlation, claim 15 of ‘302 comprising optically detectable label comprising a molecular marker-specific probe. Regarding claims 20 and 22, see’302 clai ms 20-21 (fluorophore label). Claims 6 , 7 , 17-19 , 21 and 29-33 are rejected on the ground of nonstatutory double patenting a s being unpatentable over claims 1-11 of U.S. Patent No. U.S. Patent No. 10,429,302, as applied to claim 2 above, and further in view of Schnetti et al. (cited previously above under 35 U.S.C. 103) . Regarding claim s 6 and 21 , ‘302 teach methods substantially as claimed, and although ‘302 recites surface area probe or volume probe that is a fluorophore, a fluorescent protein, etc. (‘302 claim 6), ‘302 fails to teach the species of fluorophore selected from among di-8-ANEPPS, di-4-ANEPPS, F2N12S, FM-143, Cell Mask Orange, Cell Mask Green, Cell Mask Deep Red, a carbocyanine dye or a PKH dye ; further fails to recite volume probe comprising CFSE (claim 7); fails to recite molecular-marker specific probe is a protein (claim 18), selected from those recited at claim 19 ; further fails to sample comprising at least two distinct particle species (claim 29 , claims 30-31 depend from claim 29 ) , and fails to recite particles derived from a cell, tissue, and a biological fluid (claim 32), a subject having cancer or a neurological disorder (claim 33) . Schnetti is similar to the invention of ‘302 in that Schettini et al. similarly teach (paras [001271]-[001274]) a method of analyzing particles (circulating microvesicles) in a sample (biofluids) , the method comprising:(a) contacting a sample comprising the particles with one or more optically detectable labels, thereby forming a staining solution (see dual staining with antibodies to cMV proteins and lipid-intercalating dyes to detect membranes, para [001273]) , wherein (i) the particles comprise extracellular vesicles (EVs) , and (ii) the one or more optically detectable labels comprise a surface area probe (see originally filed specification, the terminology “surface area probe” appears to include, for example cell membrane type dyes, for example di-8-ANEPPS, an art recognized cell membrane permeability dye referenced as an example of a “surface area probe”, page 34 of the originally filed specification). Schnetti teach examples of carbocyanine dyes as suitable examples of lipid staining dyes (membrane intercalating dyes), see for example paras [0015], [00554] and [001274]. It would have been prima facie obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have modified ‘302 in order to use dye such as carbocyanine dyes, as in Schnetti, as an obvious matter of using a known dye for its art recognized intended purpose, particularly because Schnetti recognize such dye as a suitable dye for staining particle membrane (surface area covered by membrane). One having ordinary skill int eh art would have a reasonable expectation of success because Schnetti is substantially similar to ‘302, Schnetti teaching this type of dye as a suitable dye for this purpose as in ‘302. Regarding claim 7, Schnetti et al. also teach examples of suitable dyes for associating with vesicle membrane, including CFSE (para [00554]. Although Schnetti does not refer to this dye as a “volume probe”, based on Applicant’s claims and originally filed specification, Schnetti, using this dye to evaluate whole microvesicles from debris, appears to be using the dye in the same manner consistent with the claims. Further, see MPEP 2112.01, "Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. a chemical composition and its properties are inseparable; in the present case, it appears that the ‘302 in view of the prior art encompasses the same probe as claimed, used on the same type of target (microvesicles) to interrogate membrane. It would have been prima facie obvious to one having ordinary skill in the art to have used CFSE, as in Schnetti, as an obvious matter of using a known dye for its art recognized intended purpose, particularly because Schnetti recognize such dye as a suitable dye for staining particle membrane (surface area covered by membrane). One having ordinary skill int eh art would have a reasonable expectation of success because Schnetti is substantially similar to ‘302, Schnetti teaching this type of dye as a suitable dye for this purpose as in ‘302. Regarding claim 17, as discussed above, ‘302 (at claim 15) recites a method substantially as claimed, however, fails to teach further contacting the particle of interest with one or more optically detectable labels comprising a surface area probe or a volume probe (see originally filed specification, the terminology “surface area probe” appears to include, for example cell membrane type dyes, for example di-8-ANEPPS, an art recognized cell membrane permeability dye referenced as an example of a “surface area probe”, page 34 of the originally filed specification). Because ‘302 fails to teach the claimed dual staining (rather claims directed to either surface area/volume probe or to molecular-marker specific probe), ‘302 fail to teach detecting the optical signal of the particle associated optically detectable labels comprising the surface area probe without physical separation or isolation of the particle of interest, determining the surface area or volume of interest based on the detected optical signal, and determining size of the particle based on the determined surface area. Schettini et al. is as referenced previously above, Schnetti teach (abstract) assessing microvesicles in a biological sample, detecting circulating biomarkers for profiling, physiological states or phenotyping (abstract). Schettini et al. teach circulating biomarkers can be associated with circulating vesicles, i.e., membrane encapsulated structures shed from cells found in bodily fluids, which can be analyzed for associated diseases (para [0007]), para [0008], Schettini teaching these structures provide a source of biomarkers, useful for diagnostic, prognostic and theranostic readout (see para [0008], teaching characteristics such as size , surface antigens, cell origin and payload as contributing to providing diagnostic, prognostic and theranostic readout). See para [0009], Schettini teach characterizing phenotype by detection biomarkers indicative of disease and disease progression. At para [001273], Schettini et al. teach as an example, using a dual staining technique, namely comprising antibodies to circulating microvesicle proteins and lipid intercalating dyes , performed in order to identify and separate circulating microvesicles from biological debris using flow cytometry. See at para [001274], Schettini teach lipid bi-layer intercalating dyes identify particles that contain lipid membranes, that since lipid dyes may also bind membrane fragments, staining for proteins known to be associated with cell plasma membranes are also included, including CD9, CD63 and CD81. At para [00231] Schettini teach, regarding flow cytometry, that this technique allows simultaneous multiparametric analysis of the physical and/or chemical characteristics of single cells flowing through a detection apparatus, that forward scatter correlates with cell size , and side scatter depends factors such as shape of nucleus, etc. I t would have been prima facie obvious to have modified the method of ‘302 to further contact the microvesicles particles with an optically detectable label comprising the surface area probe (a lipid intercalating dye, as in Schettini) because this technique would allow one to identify and separate circulating microvesicles from biological debris in the flow cytometry method (Schettini). Further, it would have been prima facie obvious, based on the further citation Schettini, to have performed forward and side scattering detection techniques, as referenced in Schettini, in order to determine the surface area of the particles, because Schettini teach size as a characteristic of interest with regard to the use of these particles for diagnostic/prognostic purposes, Schettini teaching forward scatter and side scatter provide information regarding size and shape, which one having ordinary skill in the art would expect to be valuable in techniques directed at discriminating debris from payload (antigen) carrying microvesicles in circulation. Regarding claim s 18 and 19, the combination of ‘302 in view of Schnetti is teaching molecular-marker specific probe that is a protein (antibody (a protein) binding probe to detect and bind a targeted antigen presented on a cell derived microvesicles ). See at para [001273], Schettini et al. teach as an example, using a dual staining technique, namely comprising antibodies to circulating microvesicle proteins and lipid intercalating dyes , performed in order to identify and separate circulating microvesicles from biological debris using flow cytometry. See at para [001274], Schettini teach lipid bi-layer intercalating dyes identify particles that contain lipid membranes, that since lipid dyes may also bind membrane fragments, staining for proteins known to be associated with cell plasma membranes are also included, including CD9, CD63 and CD81. Regarding claim 29, see as cited above, ‘302 recites performing the methods substantially as claimed . At the preamble of claim 29, the claim indicates “method of claim 16, wherein the samples comprise at least two distinct particle species that differ from one an