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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 05/26/2026 has been entered.
Withdrawal of Rejections
The response and amendments filed on 05/26/2026 are acknowledged. Any previously applied minor objections and/or minor rejections (i.e., formal matters), not explicitly restated here for brevity, have been withdrawn necessitated by Applicant’s formality correction and/or amendments. For the purposes of clarity of the record, the reasons for the Examiner’s withdrawal, and/or maintaining, if applicable, of the substantive or essential claim rejections are detailed directly below and/or in the Examiner’s Response to Arguments section.
Briefly, the previous 35 U.S.C 102 rejection has been withdrawn necessitated by Applicant’s arguments; however, new grounds of rejection are set forth below. The previous 35 U.S.C. 103 rejections have been withdrawn; however, new grounds of rejection have been set forth below.
The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Claim Rejections - 35 USC § 112(a), Written Description
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claims 1-13 are rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Independent claim 1 recites “A method of analyzing a fluid sample to determine an amount of a target component in the fluid sample”. Independent claim 8 recites “A method of analyzing a fluid that includes a target component”. Applicant is broadly claiming any fluid sample with any functional group.
With regards to the written description pertaining to “fluid sample”, the instant specification states “this disclosure provides a method of analyzing a fluid sample to determine the amount of a target component in the fluid sample. The method includes combining a first group of beads with the fluid sample and combining a second group of beads with the fluid sample” (see, e.g., instant specification, [0007]). The instant specification states “this disclosure provides a method of analyzing a fluid that includes a target component” (see, e.g., instant specification, [0008]). Therefore, based on the specification, the fluid sample can be any fluid sample as long as it contains a target component. With regards to the written description pertaining to “target component”, the instant specification states “the target(s) of interest in the sample can include a population of cells, such as specific microorganisms (e.g., coliforms including e coli, legionella, pseudomonas, enterococcus, giardia, cryptosporidium, etc.). The target can also include live ones of the microorganisms and/or dead ones of the microorganisms. Alternatively, the target(s) can include particles or chemical compounds of interest in the sample” (see, e.g., instant specification, [0015]). Based on the instant specification, the target component can be any microorganism (alive or dead), any cell (alive or dead), or any particle or chemical compound of interest. Applicant’s disclosure does not provide a representative number of species or a reasonable structure-function correlation for the claimed genera – “fluid sample” and “target component”. Based on Applicant’s disclosure, one would not know what surface functional group(s) bind to what target component(s), as Applicant has not set forth a reasonable structure-function correlation. Furthermore, Applicant has not set forth a representative number of species for the types of fluid samples containing target components because Applicant does not disclose specific fluid samples that can be used in this method. Additionally, Applicant’s disclosure that the target component can be microorganisms, cells, and particles or chemicals, is not sufficient for the claimed genus since there can be other target components, especially unknown/undiscovered target components, that can be detected using this method.
The instant specification states that “the beads can be functionalized with antibodies, antibody conjugates, aptamers, DNAzmes, molecular imprinted polymers, heme groups, etc.” (see, e.g., instant specification, [0016]). Therefore, if the surface functional group is antibodies, the prior art teaches that “relatively limited group of antibodies that can penetrate cell membranes, most antibodies targeted to promising intracellular targets do not demonstrate cell-penetrating ability, making their delivery inside a cell a key bottleneck” (see, e.g., Slastnikova, “Targeted Intracellular Delivery of Antibodies: The State of the Art”; 2018) Therefore, based on the teachings of the prior art, it is unpredictable as to whether all cells, which include intracellular targets, can be used in this method when the surface functional group is antibodies and the target component is intracellular (see, e.g., MPEP 2163(II)(3)(ii) – “[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated."). Furthermore, based on the prior art, it is unpredictable as to what target components can and cannot be detected using this method, and Applicant’s disclosure does not provide written description or guidance for this because, as discussed above, Applicant does not provide a representative number of species for fluid samples and target components, nor does the Applicant provide reasonable structure-function correlation for what target components bind to what surface functional groups. Without contemplation or guidance provided of what targets can bind to what functional groups, applicant does not have written description for all targets and all functional groups including those that have not been discovered. Applicant is broadly claiming fluid samples and target components; however, the prior art clearly shows that there is unpredictability as to what fluid samples containing target components can be targeted with antibodies as the surface functional group.
Therefore, the instant specification and prior art does not provide support for the possession of the entire claimed “fluid sample” and “target component” genera.
Claim Rejections - 35 USC § 102, Anticipation
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1 and 4 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lindmo (Immunometric assay by flow cytometry using mixtures of two particles of different affinity; 1989 – previously cited).
Claim Interpretation: The “same functional group” as contemplated by the specification requires that the ‘group’ can bind to the same target. Thus, this interpretation has been applied, i.e. the first and second bead groups to be functionalized to the same target component. Additionally, it has been interpreted that that any beads that bind to the same target component have the same surface functional group.
Lindmo’s general disclosure relates to “An improved dynamic range in a particle based flow cytometric immunoassay for carcinoembryonic antigen (CEA) was obtained using a binary mixture of two distinguishable particle types, namely particles of 7 and 10 µm diameter that were distinguishable by their light scattering characteristics in the flow cytometer. The two particle types were coated with antibody of the same specificity but different affinity” (see, e.g., Lindmo, abstract). Moreover, Lindmo discloses measuring fluorescence by flow cytometry to determine the fluorescence intensity of the two particles (see, e.g., Lindmo, abstract). Furthermore, Lindmo discloses “The two particle types are distinguishable in the flow cytometer, and therefore the particle-associated fluorescence can be determined separately for each particle type. At low antigen concentrations, binding will preferentially occur on the high affinity particles. On the other hand, the low affinity particles will show an increase in binding with increasing antigen concentration even after binding to the high affinity particles has been saturated. This results in an increased dynamic range for the assay, without compromising the high sensitivity provided by the high-affinity particle” (see, e.g., Lindmo, Introduction, pg. 184).
Regarding claim 1 pertaining to a method of analyzing a fluid sample, Lindmo teaches “An improved dynamic range in a particle based flow cytometric immunoassay for carcinoembryonic antigen (CEA) was obtained using a binary mixture of two distinguishable particle types, namely particles of 7 and 10 µm diameter that were distinguishable by their light scattering characteristics in the flow cytometer. The two particle types were coated with antibody of the same specificity because they both bind to CEA. Furthermore, Lindmo teaches functionalization of the two different sized particles with two IgG1 antibodies that both target the CEA antigen (see, e.g., Lindmo, “Monoclonal antibodies”, pg. 184). . Therefore, Lindmo teaches a mixture of two bead groups, that are two different sizes and that bind to the same target component, wherein the target component is CEA; therefore, the two different sized bead groups are both coated with anti-CEA monoclonal antibodies and are therefore both surface functionalized against the same CEA target component (see, e.g., Lindmo, Materials and Method – “Monoclonal antibodies”). Furthermore, Lindmo teaches “A dilution series of CEA samples was incubated with aliquots of the particle mixture and secondary biotin-streptavidin-phycoerythrin-conjugated antibody directed against a different epitope on the CEA molecule. The fluorescence intensity of the two particle types was measured flow cytometrically, and a double standard curve plotted from the mean logarithmic fluorescence values (see, e.g., Lindmo, abstract). Moreover, Lindmo teaches “The present method using a binary mixture of two distinguishable particle types coated with antibodies of the same specificity, but of different affinity, and measuring the amount of binding to each type of particle, provides an assay with a larger dynamic range than that obtained from the use of only one particle type” (see, e.g., Lindmo, Discussion, pg. 187). Therefore, Lindmo teaches binding of the same surface functional group on the different sized beads to CEA, labeling CEA with a secondary biotin-streptavidin-phycoerythrin-conjugated antibody, followed by flow cytometry to measure the amount of binding to each type of particle.
Regarding claim 4 pertaining to detecting fluorescence emission, Lindmo teaches “Samples were analysed in a Coulter Epics V flow cytometer (Coulter Epics Division, Hialeah, FL) using 600 mW of the 488 nm line from an Argon ion laser for excitation of PE fluorescence. Detection was in the region 550-590 nm. Separate histograms of logarithmic fluorescence intensity representing the two particle types MP7 and MP10 were acquired by means of gating on windows set in the light scatter histogram for each of the two populations” (see, e.g., Lindmo, “Flow cytometry analysis”, pgs. 185-186).
Examiner’s Response to Arguments
Regarding Applicant’s arguments pertaining to the previous 35 U.S.C. 102 rejection in view of Haquette (remarks, pages 5-8), as mentioned above, all previous 35 U.S.C. 102 rejections were withdrawn; however, new grounds of rejection are set forth above in view of Lindmo. Therefore, Applicant’s arguments are moot.
Claim Rejections - 35 USC § 102/103
Claims 8 and 11 are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Lindmo (Immunometric assay by flow cytometry using mixtures of two particles of different affinity; 1989 – previously cited).
Claim interpretation: The Examiner has interpreted “same surface functional group” for the two different sized bead groups, as recited in claim 8, to mean that the two different sized bead groups are functionalized against the same target component (as contemplated in the specification) and any bead that binds to the same target component has the same surface functional group. Moreover, the Examiner has interpreted that the same surface functional group can be, for example, the same class of antibody (i.e., IgG antibodies) that binds to the same target component since IgG antibodies are a group of antibodies which can comprise a surface functional group. For compact prosecution the rejection is made under 102/103.
The teachings of Lindmo are discussed above as it pertains to a method of analyzing a fluid sample to determine the amount of a target component by employing different sized microspheres that contain the same or a substantially similar functional group.
Regarding claim 8 pertaining to a method of analyzing a fluid sample, Lindmo teaches “An improved dynamic range in a particle based flow cytometric immunoassay for carcinoembryonic antigen (CEA) was obtained using a binary mixture of two distinguishable particle types, namely particles of 7 and 10 µm diameter that were distinguishable by their light scattering characteristics in the flow cytometer. The two particle types were coated with antibody of the same specificity because they both bind to CEA. Moreover, Lindmo teaches that the 7 µm particle is coated with an IgG2a antibody against CEA, the 10 µm particle is coated with an IgG1 antibody against CEA, and a third antibody which is IgG1 was used to label another epitope of CEA (see, e.g., Lindmo, “Monoclonal antibodies”, pg. 184); therefore, all bead groups are functionalized with anti-CEA antibodies and all bead groups bind to CEA as the target component. Furthermore, Lindmo teaches functionalization of the bead groups with two IgG1 antibodies against CEA (see, e.g., Lindmo, “Monoclonal antibodies”, pg. 184). Therefore, Lindmo teaches a mixture of two bead groups, that are two different sizes, but that bind to the same target component, wherein the target component is CEA; therefore, the two different sized bead groups are both coated with anti-CEA monoclonal antibodies and are therefore both surface functionalized against the same CEA target component (see, e.g., Lindmo, Materials and Method – “Monoclonal antibodies”). Furthermore, Lindmo teaches “A dilution series of CEA samples was incubated with aliquots of the particle mixture and secondary biotin-streptavidin-phycoerythrin-conjugated antibody directed against a different epitope on the CEA molecule. The fluorescence intensity of the two particle types was measured flow cytometrically, and a double standard curve plotted from the mean logarithmic fluorescence values (see, e.g., Lindmo, abstract). Furthermore, the high affinity particles exhibited higher fluorescence than the larger, low affinity particles (see, e.g., Lindmo, “Results”, pg. 186); therefore, exhibiting differences in CEA affinities to the particles. Moreover, Lindmo teaches “The present method using a binary mixture of two distinguishable particle types coated with antibodies of the same specificity, but of different affinity, and measuring the amount of binding to each type of particle, provides an assay with a larger dynamic range than that obtained from the use of only one particle type” (see, e.g., Lindmo, Discussion, pg. 187). Therefore, Lindmo teaches binding of the same surface functional group on the different sized beads to CEA, labeling CEA with a secondary biotin-streptavidin-phycoerythrin-conjugated antibody, followed by flow cytometry to measure the amount of binding to each type of particle.
Regarding claim 11 pertaining to the bead groups, Lindmo teaches two bead groups (see, e.g., Lindmo, abstract).
In the alternative, if the surface functional group taught by Lindmo are not one and the same and for compact prosecution and applicant’s term “same group”, the claims are rendered obvious since Lindmo teaches that the particles are coated with antibodies against the same surface functional group and these antibodies have a substantially similar structure. More specifically, Lindmo teaches that the smaller 7 µm particle is coated with an IgG2a antibody against CEA and that the larger 10 µm particle is coated with an IgG1 antibody against CEA (see, e.g., Lindmo, “Monoclonal antibodies”, pg. 184). Both antibodies used to coat the different sized particles are IgG antibodies against CEA; therefore, these antibodies belong to the same IgG group (i.e., same surface functional group and same antibody group) and the antibodies vary slightly in their hinge region (see, e.g., Vidarsson; Art of Record). Furthermore, the hinge region does not affect antibody specificity (i.e., the antibodies are still able to bind to the same target component), as evidenced by Lindmo; therefore, regardless of IgG isotype, the antibodies are still bind to the same target component and still comprise the same surface functional group (i.e., IgG antibody class against CEA antigen). Therefore, it would be obvious to use the same IgG isotype for surface functionalization since the antibodies taught by Lindmo all bind to the same target component which is the critical feature as contemplated by the specification. Additionally, Lindmo teaches a third antibody which is IgG1 was used to label another epitope of CEA (see, e.g., Lindmo, “Monoclonal antibodies”, pg. 184); therefore, Lindmo teaches two IgG1 antibodies that bind to CEA, which reads upon the instantly claimed invention.
Thus, the claimed invention, as whole, was clearly prima facie obvious especially in the absence of sufficient, clear, and convincing evidence to the contrary.
Examiner’s Response to Arguments
Regarding Applicant’s arguments pertaining to the previous 35 U.S.C. 102 rejection in view of Haquette (remarks, pages 5-8), as mentioned above, all previous 35 U.S.C. 102 rejections were withdrawn; however, new grounds of rejection are set forth above in view of Lindmo. Therefore, Applicant’s arguments are moot.
Claim Rejections - 35 USC § 103, Obviousness
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 3, 5-6, 9, and 12-13 are rejected under 35 U.S.C. 103 as being unpatentable over Lindmo as applied to claims 1, 4, 8, and 11 above, and further in view of Haquette (US 2006/0292552; Date of Publication: December 28, 2006 – previously cited).
The teachings of Lindmo are discussed above as it pertains to a method of analyzing a fluid sample to determine the amount of a target component by employing different sized microspheres that contain the same or a substantially similar functional group.
However, Lindmo does not teach: wherein the beads are magnetic beads, and the step of separating includes magnetically separating the first and second group of beads from the fluid sample (claim 3); or wherein the fluid sample includes water, and the target component is a microorganism (claim 5); or wherein the fluorescence marker includes a dye that differentiates live ones of the microorganism from dead ones of the microorganism (claim 6); or determining, based on the detected size and fluorescence or colorimetric properties of the beads, a number of beads in each of the at least two bead groups that includes the target component (claim 9); or wherein the at least two bead groups includes 3 to 10 bead groups (claim 12); or further comprising separating the beads of the at least two bead groups from the fluid sample prior to the step of introducing the beads into the flow cytometer (claim 13).
Haquette’s general disclosure pertains to “a method for the detection and multiplex quantification of analytes in a sample, using functionalised microspheres, whereby said microspheres are magnetised after the sample has been brought into contact therewith. The inventive method is particularly suitable for the detection and multiplex quantification of several analytes by means of flow cytometry” (see, e.g., Haquette, abstract). Moreover, Haquette discloses that the microspheres can be functionalized with, for example, antibodies that bind surface structures of microorganisms in liquid samples (see, e.g., Haquette, [0120]-[0121]). Furthermore, Haquette teaches that the antibody can contain a fluorescent label so that the sample can be analyzed using flow cytometry in order to determine the number of analytes within the sample (see, e.g., Haquette, [0120]-[0122]).
Regarding claim 3 pertaining to the magnetic beads, Haquette teaches that magnetic particles are added to the medium which causes them to bind to the surface of the microsphere (see, e.g., Haquette, [0120]). Furthermore, Haquette teaches “the microspheres thus made magnetizable can be separated from the other interfering products of the medium by means of one or more magnetization steps alternating with one or more steps consisting in washing with an appropriate buffer” (see, e.g., Haquette, [0120]).
Regarding claim 5 pertaining to the fluid sample, Haquette teaches that the sample may be present in a liquid and may contain any microorganism (see, e.g., Haquette, [0044]-[0045]). One of ordinary skill in the art would readily understand that the sample, being a liquid, can include water.
Regarding claim 6 pertaining to the fluorescence marker, Haquette teaches that fluorescein, which is a dye that differentiates live and dead microorganisms, can be used as a dye (see, e.g., Haquette, [0092]).
Regarding claim 9 pertaining to determining the number of beads, Haquette teaches that when analyzing the samples with flow cytometry, the number of events for each of the beads is counted (see, e.g., Haquette, [0259], Figures 34-36, 39-40); therefore, one of ordinary skill in the art would understand that each of these events is correlated to the number of beads counted.
Regarding claims 12 pertaining to the bead groups, Haquette teaches, for example, “that there are three populations of latex microspheres (three analytes to be detected and/or quantified) of different sizes” (see, e.g., Haquette, [0120]).
Regarding claim 13 pertaining to separating and analyzing the beads, Haquette teaches “The microspheres thus made magnetizable can be separated from the other interfering products of the medium by means of one or more magnetization steps alternating with one or more steps consisting in washing with an appropriate buffer” (see, e.g., Haquette, [0120]). Haquette teaches that “the microspheres associated with the fluorochrome can be analyzed. In the present case, they are analyzed by flow cytometry according to their size” (see, e.g., Haquette, [0122]).
It would have been first obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to perform Lindmo’s method of coating two different sized particles with antibodies of the same specificity, wherein the particles are magnetizable, as taught by Haquette. One would have been motivated to do so because Haquette teaches that magnetizable particles allows for a magnetic separation step to take place, which “makes it possible to facilitate the assays in certain complex media where the antigens of interest must be specifically isolated (it being possible for a cytometric analysis to prove impossible to carry out in the presence of certain microparticles). This is the case, for example, for analyses in agrofoods, paper-making and wastewater treatment, where molecules/particles present in various liquefied ground materials (pulps, musts, dairy products or even cheeses, fruit juices, ground vegetable materials, fermentation liquors, etc.) are investigated, which preparations cannot be filtered because of the risk of losing the analyte to be assayed” (see, e.g., Haquette, [0013]). Furthermore, Haquette teaches that magnetizing the particles allows for the use of magnetic separation of the particles in order to rapidly concentrate the agents to be assayed and prevents having to use centrifugation steps for washing the trapped beads (see, e.g., Haquette, [0015]). Moreover, Lindmo teaches a particle based cytometric immunoassay for CEA by mixing two particles of different sizes that are coated with the same specificity, but different affinity, so that the particles are distinguishable by their light scattering characteristics in the flow cytometer due to their different sizes (see, e.g., Lindmo, abstract). Therefore, based on the teachings of Lindo and Haquette, it would have been obvious to make Lindmo’s particles magnetizable, as taught by Haquette, in order to be able to separate the particles using magnetic separation in order to concentrate the particles bound to CEA for subsequent flow cytometry analysis.
It would have been secondly obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to perform Lindmo’s method of coating two different sized particles with antibodies of the same specificity that bind to a specific target component in a fluid sample, wherein the target component is a microorganism, as taught by Haquette. One would have been motivated to do so because Haquette teaches that the target component can be a microorganism, such as a bacterium or virus (see, e.g., Haquette, [0048]), wherein the microspheres can be functionalized against the microorganism in order to rapidly detect and quantify the microorganisms in a sample (see, e.g., Haquette, abstract & [0001]). Moreover, Lindmo teaches a particle based cytometric immunoassay for CEA by mixing two particles of different sizes that are coated with the same specificity, but different affinity, so that the particles are distinguishable by their light scattering characteristics in the flow cytometer due to their different sizes (see, e.g., Lindmo, abstract). Therefore, based on the teachings of Lindmo and Haquette, it would have been obvious to functionalize Lindmo’s different sized particles against microorganisms in order to quantify the number of microorganisms in a sample.
It would have been thirdly obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to perform Lindmo’s method of coating two different sized particles with antibodies of the same specificity that bind to a specific target component in a fluid sample, wherein the target component, which can be a microorganism, is labelled with a dye that differentiates live and dead microorganisms, as taught by Haquette. One would have been motivated to do so because Haquette teaches that labelling the analyte (i.e., microorganism) with a fluorescent marker allows for the analyte to be detected and quantified using flow cytometry (see, e.g., Haquette, [0092]-[0094]). One of ordinary skill in the art would readily understand that using a fluorescent marker that differentiates live and dead microorganisms allows for differentiation of live and dead microorganisms that find to the functionalized particle using flow cytometry. Moreover, Lindmo teaches a particle based cytometric immunoassay for CEA by mixing two particles of different sizes that are coated with the same specificity, but different affinity, so that the particles are distinguishable by their light scattering characteristics in the flow cytometer due to their different sizes (see, e.g., Lindmo, abstract). Therefore, based on the teachings of Lindmo and Haquette, it would have been obvious to label the target microorganism with a fluorescent dye that differentiates between live and dead microorganisms in order to quantify the number of live and dead microorganisms in a fluid sample.
It would have been fourthly obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to perform Lindmo’s method of coating different sized particles with antibodies of the same specificity that bind to a specific target component in a fluid sample, wherein there are at least three particles, as taught by Haquette. One would have been motivated to do so because Haquette teaches increasing the number of beads allows one to increase the number of analytes to be detected or quantified (see, e.g., Haquette, [0120]). Moreover, Lindmo teaches that “The present report describes an immunometric assay for flow cytometric reading based on a mixture of two distinguishable types of particle, e.g., of different size. In this approach the hook effect is largely eliminated by using two types of particle coated with antibody of the same specificity, but different affinity. The two particle types are distinguishable in the flow cytometer, and therefore the particle-associated fluorescence can
be determined separately for each particle type. At low antigen concentrations, binding will preferentially occur on the high affinity particles. On the other hand, the low affinity particles will show an increase in binding with increasing antigen concentration even after binding to the high affinity particles has been saturated. This results in an increased dynamic range for the assay, without compromising the high sensitivity provided by the high-affinity particle” (see, e.g., Lindmo, Introduction, pg. 184). Therefore, based on the teachings of Lindmo and Haquette, it would have been obvious to increase the number of particles, as taught by Haquette, while keeping the same specificity and different affinities, as taught by Lindmo, in order to decrease the hook effect. Moreover, Lindmo and Haquette still teach that the different sized particles, regardless of number, are able to be distinguished using flow cytometry, which allows for identification and quantification of a specific target component. One would have expected success because Haquette and Lindmo both teach surface-functionalized particles of different sizes for binding to target components.
Claims 2, 7 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Lindmo and Haquette as applied to claims 1, 4, 3, 5-6, 8-9, and 11-13 above, and further in view of Cormican (EP2009110; Date of Publication: December 31, 2008 – cited in the IDS filed on 04/07/2023 – previously cited).
The teachings of Lindmo and Haquette, herein referred to as modified-Lindmo-Haquette, are discussed above as it pertains to a method of analyzing a fluid sample to determine the amount of a target component by employing different sized microspheres that contain the same or a substantially similar functional group.
Regarding claims 2 and 10 pertaining to the determined number of beads in the first and second groups of beads that includes the target component, modified-Lindmo-Haquette teaches that when analyzing the samples with flow cytometry, the number of events for each of the beads is counted (see, e.g., Haquette, [0259], Figures 34-36, 39-40); therefore, one of ordinary skill in the art would understand that each of these events is correlated to the number of beads counted.
However, modified-Lindmo-Haquette does not teach: determining the MPN of the target component (claims 2 and 10); or further comprising determining the most probable number (MPN) of the live microorganisms in the fluid sample and the most probable number (MPN) of the dead microorganisms in the fluid sample (claim 7).
Cormican’s general disclosure pertains to “Rapid enumeration of antimicrobial resistant organisms using the Most Probable Number method. The invention provides processes that can be used to examine the occurrence of antimicrobial resistant organisms in water and effluent, and other liquidised substances such as a suspension, e.g. food, soil, faeces etc. The method is capable of detecting antimicrobial resistant microbes in a number of samples simultaneously” (see, e.g., Cormican, abstract). Moreover, Cormican discloses “The Most Probable Number (MPN) method is routinely used worldwide in the field of Environmental Microbiology to detect and enumerate coliforms, E. coli and Enterococci in water samples. The MPN method is not an exact count of the numbers of bacteria present in a given sample, but rather an estimate of the most probable number of bacteria in a particular volume of sample. Traditionally this is performed using three sets of tubes with 3 or 5 tubes per set. The first set generally contains 10ml of double strength broth and each tube in the set is inoculated with 10ml of sample. The second and third sets of tubes contain 10ml of single strength broth and each tube in these sets is inoculated with 1ml and 0.1ml of sample respectively. Following incubation the pattern of growth is compared with a table of statistically determined most probable numbers” (see, e.g., Cormican, [0011]).
Regarding claims 2 and 10 pertaining to the MPN of the target component, Cormican teaches a method of determining the most MPN of a microorganisms present in a solution by incubating the microorganisms with an indicator, such as o-nitrophenyl-beta-D-galactopyranoside (ONPG) and 4-methylumbeilliferyl-beta-D-glucuronide (MUG), which is metabolized by the microorganism and creates fluorescence (see, e.g., Cormican, [0023]). Furthermore, Cormican teaches that “the MPN of organisms present determined by comparison with a predefined table” (see, e.g., Cormican, [0025]). Moreover, Cormican teaches “The method is equally effective for aqueous samples, such as water, seawater, environmental, effluent and even aqueous biological samples such as blood, urine and sputum” (see, e.g., Cormican, [0026]).
Regarding claim 7 pertaining to the MPN of the live and dead microorganisms, Cormican teaches a method of determining the most MPN of a microorganisms present in a solution by incubating the microorganisms with an indicator, such as o-nitrophenyl-beta-D-galactopyranoside (ONPG) and 4-methylumbeilliferyl-beta-D-glucuronide (MUG), which is metabolized by the microorganism and creates fluorescence (see, e.g., Cormican, [0023]). Moreover, Cormican teaches incubating the microorganisms with antibiotics to determine the proportion of antimicrobial resistant organisms in the sample, compared to a control sample (see, e.g., Cormican, [0022]). One of ordinary skill in the art would recognize that treating the microorganisms with antibiotics will results in some of the microorganisms dying, while some living, if they are resistant. Therefore, Cormican is determining the MPN of live and MPN of dead microorganisms in the sample.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to apply modified-Lindmo-Haquette’s method of analyzing a fluid sample containing microorganisms by determining the amount of a target component in a fluid sample through the use of magnetic, functionalized bead groups, to Cormican’s method of determining the MPN of the microorganisms. One would have been motivated to do so because Cormican teaches that determining the MPN is a rapid test (see, e.g., Cormican, [0013]), that involves incubating the microorganisms with an indicator, such as o-nitrophenyl-beta-D-galactopyranoside (ONPG) and 4-methylumbeilliferyl-beta-D-glucuronide (MUG), which is metabolized by the microorganism and creates fluorescence in order to determine the number of microorganisms in the sample (see, e.g., Cormican, [0023]). Additionally, modified-Lindmo-Haquette teaches a method of analyzing a microorganism fluid sample, wherein the microorganisms are “tagged” with microspheres that are functionalized for binding to specific structures on the microorganisms (see, e.g., Haquette, [0120]-[0122]). Furthermore, modified-Lindmo-Haquette teaches that the microspheres are fluorescently tagged so that a count of the number of target components can be established using flow cytometry (see, e.g., Haquette, [0120]-[0122]). Therefore, based on the teachings of modified-Lindmo-Haquette and Cormican, it would have been obvious to apply modified-Lindmo-Haquette’s method of analyzing a fluid sample to Cormican’s method of determining the MPN of a microorganism because this would allow one to determine the number of microorganisms in a sample by measuring the fluorescence of the microorganism using flow cytometry. One would have expected success because modified-Lindmo-Haquette and Cormican both teach methods of measuring the number of microorganisms in a liquid sample.
Examiner’s Response to Arguments
Regarding Applicant’s arguments pertaining to the previous 35 U.S.C. 103 rejection in view of Lindmo (remarks, pages 5-8), as mentioned above, all previous 35 U.S.C. 103 rejections were withdrawn; however, new grounds of rejection are set forth above in view of Haquette and Cormican. Therefore, Applicant’s arguments are moot.
Art of Record
Vidarsson G, Dekkers G, Rispens T. IgG subclasses and allotypes: from structure to effector functions. Front Immunol. 2014 Oct 20;5:520. doi: 10.3389/fimmu.2014.00520. PMID: 25368619; PMCID: PMC4202688.
Conclusions
Claims 1-13 are rejected.
No claims are allowed.
Correspondence Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NATALIE IANNUZO whose telephone number is (703)756-5559. The examiner can normally be reached Mon - Fri: 8:30-6:00 EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sharmila Landau can be reached at (571) 272-0614. 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.
/NATALIE IANNUZO/Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653
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