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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 01/17/2025 and 06/06/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Objections
Claims 3, 7, and 14 are objected to because of the following informalities: the acronyms “CSF” in claim 3; “PCR”, “LCR”, and “RCA” in claim 7; and “CRP” in claim 14 need to be fully written-out, followed by an abbreviation of the term in parentheses. Appropriate correction is required.
Claims 2-20 are objected to because of the following informalities: it is suggested to insert a comma after the claim numbers for respective dependent claims. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 4 and 8 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. Claim 4 recite the following limitation: “a mucus removal reagent”. The specification of the instant application does not mention a mucus removal reagent, however, it is included in claim 4 of the application. Moreover, claim 8 is rejected under 112(a) since it depends on claim 4 of the instant application.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-20 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. In particular, in claim 1, the term “powerless heat source” is unclear, since in order to power something or form something to have power, it requires the production of such, however, applicant’s term “powerless heat source” appears to contradict the typical definition. Regarding claim 2, term “self-powered without any external electrical power source” also further contradicts the definition of the description. That is, the language of said claim allow for an electrical power source, such as a battery, to be present in the device, such as a battery that may received power or be charged by an external device and then uncoupled and placed in the device of the claimed invention. The unclarity is noted in the specification, para. [0057] of the instant application. Moreover, the term “self-powered” is also not considered with the dictionary or known meaning of the term. Therefore, the dependent claims, 2-20 of the instant application are indefinite as it is unclear as to what applicant is attempting to claim and convey.
Regarding claims 10 and 14, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-20 are rejected under 35 U.S.C. 103 as being unpatentable over US 2021/0199651 A1-Zenhausern et al. (hereinafter “Zenhausern”, has an earlier effective filing date as of the provisional application), and further in view of US 2009/0004732 A1-LaBarre et al. (hereinafter “LaBarre”).
Regarding claim 1, Zenhausern discloses a device for self-testing for a plurality of biomarkers (various vertical flow-oriented devices and systems for detecting biomarkers, para. [0005], lines 1-2; abstract lines 1-2) comprising: a sample inlet configured to receive a liquid biofluid sample (VFI system of device 1 comprises a membrane 3, Fig. 2A; including a flow through area is 10mm in diameter encapsulated in a stainless steel filter holder 29, Fig. 2A; para. [0095], lines 7-8; also, Fig. 2A shows a sample inlet configured to receive a liquid biofluid sample);
“a sample pre-processing module fluidically connected to the sample inlet to provide a pre-processed biofluid sample (Zenhausern discloses the device 1 will process in four steps, performing the multiplex pathogens assay, recording the biomarkers interactions and performing the analysis required to provide a diagnostic result: 1. Biofluid filtering and pre-processing (e.g. serum and plasma separation, para. [0282], lines 3-8; A pre-filtration through 0.2 um Polyethersulfone (PES) membrane is preferred to remove any micro-particles and cellular components that might clog the VFI membrane 3, para. [0217], lines 9-12);
“a filter in fluidic contact with the liquid biofluid sample or the pre- processing module to provide a filtered fluid sample (Zenhausern discloses a pre-filtration through 0.2 um Polyethersulfone (PES) membrane is preferred to remove any micro-particles and cellular components that might clog the VFI membrane 3, para. [0217], lines 9-12; the sample will be pre-filtered before going into the detection membrane 3. The pre-filter 56 can be external, or together with the sample tube/holder 59, para. [0228], lines 12-14);”
“a vertical flow biosensor (VFB) comprising a multiplex membrane in fluidic contact with the pre-processed biofluid sample for multiplex detection of the plurality biomarkers in the liquid biofluid sample (Zenhausern discloses analysis of paper-based immuno-biosensor: FIG. 1A illustrates the principle of a paper-based immuno-biosensor in the vertical flow format, as used in the disclosed vertical flow detection device 1, para. [0095], lines 1-4).”
Regarding claim 1, Zenhausern teaches the invention discussed above. However, Zenhausern does not explicitly teach a powerless heat source in thermal contact with the pre-processed biofluid sample and/or the filtered fluid sample for controlled temperature of the pre-processed biofluid sample and/or filtered fluid sample.
LaBarre teaches an invention relating to diagnostic devices, more specifically to non-instrumented biochemical diagnostic devices (para. [0005]) and exothermic and/or endothermic chemical reactions in combination with phase change materials can produce output temperature(s, abstract). Also, LaBarre teaches an assay platform comprises a heating element and a reaction vessel. The heating element comprises an exothermic phase change material that generates heat as a consequence of crystallizing a supercooled liquid and generates heat at a constant temperature as a con sequence of the liquid form of the exothermic phase change material being in equilibrium with the solid form of the exothermic phase change material (para. [0012]), which reads on the instant claim limitation of a powerless heat source in thermal contact with the pre-processed biofluid sample and/or the filtered fluid sample for controlled temperature of the pre-processed biofluid sample and/or filtered fluid sample.
It would have been obvious to a person having ordinary skill in the art before the effective filing date of the invention to take the device of Zenhausern and further include a powerless heat source in thermal contact with the pre-processed biofluid sample and/or the filtered fluid sample for controlled temperature of the pre-processed biofluid sample and/or filtered fluid sample as taught by LaBarre in order to permit controlled temperature of the pre-processed biofluid sample and/or filtered fluid sample, therefore, increasing the effectiveness of the device (para. [0069] and para. [0099]).
Regarding claim 2, Zenhausern teaches the invention discussed above in claim 1. However, Zenhausern does not explicitly teach a device self-powered without any external electrical power source.
LaBarre teaches an invention relating to diagnostic devices, more specifically to non-instrumented biochemical diagnostic devices (para. [0005]) and exothermic and/or endothermic chemical reactions in combination with phase change materials can produce output temperature(s, abstract). Also, LaBarre teaches an assay platform comprises a heating element and a reaction vessel. The heating element comprises an exothermic phase change material that generates heat as a consequence of crystallizing a supercooled liquid and generates heat at a constant temperature as a con sequence of the liquid form of the exothermic phase change material being in equilibrium with the solid form of the exothermic phase change material (para. [0012]), which reads on the instant claim limitation of a device self-powered without any external electrical power source.
It would have been obvious to a person having ordinary skill in the art before the effective filing date of the invention to take the device of Zenhausern and further include a device self-powered without any external electrical power source as taught by LaBarre in order to permit controlled temperature of the pre-processed biofluid sample and/or filtered fluid sample, therefore, increasing the effectiveness of the device (para. [0069] and para. [0099]).
Regarding claim 3, Zenhausern discloses wherein the liquid biofluid sample is a saliva sample, a plasma sample, a blood sample, a urine sample, a sputum sample, a semen sample, a vaginal discharge sample, a tear fluid, a breath condensation droplet, a CSF fluid biopsy or plural effusion (biofluids such as blood, para. [0235]).
Regarding claim 4, Zenhausern discloses wherein the sample pre-processing module comprises one or more of: the filter in fluidic contact with the liquid biofluid sample to provide the pre- processed biofluid sample that is the filtered biofluid sample; a mucus removal reagent (MRR) fluidically connected to the sample inlet to introduce the MRR to the liquid biofluid sample that is a saliva sample, wherein MRR removes mucus from the saliva sample and reduces a viscosity of the saliva sample; a rheological property adjuster; a pH adjuster; a concentration adjuster; or an interaction force modulator (a pre-filtration through 0.2 um polyethersulfone (PES) membrane is preferred to remove any micro-particles and cellular components that might clog the VFI membrane 3, para. [0217], lines 9-12; the sample will be pre-filtered before going into the detection membrane 3. The pre-filter 56 can be external, or together with the sample tube/holder 59, para. [0228], lines 12-14).
Regarding claim 5, Zenhausern discloses wherein the plurality of biomarkers comprises one or more of: one or more markers of an infectious agent and fragments thereof, including polypeptides and/or polynucleotides; one or more markers of a host immune response; one or more vaccine markers; one or more cancer biomarkers; one or more nutrition or metabolic biomarkers; one or more auto-immune disorder biomarkers; one or more cardiovascular biomarkers; one or more genetic disorder biomarkers; or one or more environmental biomarkers (Biomarkers (LPS , PGA , FI ) are purchased commercially, para. [0147]).
Regarding claim 6, Zenhausern teaches the invention discussed above in claim 1. However, Zenhausern does not explicitly teach wherein the powerless heat source comprises: a chemical heat source comprising reagents for an exothermic chemical reaction to provide a biological sample temperature range of between 34°C and 95°C to activate at least one step of an amplification reaction of a biological component in the liquid biofluid sample.
LaBarre teaches an invention relating to diagnostic devices, more specifically to non-instrumented biochemical diagnostic devices (para. [0005]) and exothermic and/or endothermic chemical reactions in combination with phase change materials can produce output temperature(s, abstract). Also, LaBarre teaches an assay platform comprises a heating element and a reaction vessel. The heating element comprises an exothermic phase change material that generates heat as a consequence of crystallizing a supercooled liquid and generates heat at a constant temperature as a con sequence of the liquid form of the exothermic phase change material being in equilibrium with the solid form of the exothermic phase change material (para. [0012]). Additionally, LaBarre teaches exothermic reactions bringing two reaction components in close contact. Such mixtures can achieve temperatures ranging from slightly above body temperature to over to 100° C (where body temperature can range from 36.1°C to 37.2°C), which reads on the instant claim limitation of wherein the powerless heat source comprises: a chemical heat source comprising reagents for an exothermic chemical reaction to provide a biological sample temperature range of between 34°C and 95°C to activate at least one step of an amplification reaction of a biological component in the liquid biofluid sample.
It would have been obvious to a person having ordinary skill in the art before the effective filing date of the invention to take the device of Zenhausern and further include wherein the powerless heat source comprises: a chemical heat source comprising reagents for an exothermic chemical reaction to provide a biological sample temperature range of between 34°C and 95°C to activate at least one step of an amplification reaction of a biological component in the liquid biofluid sample as taught by LaBarre in order to permit controlled temperature of the pre-processed biofluid sample and/or filtered fluid sample, therefore, increasing the effectiveness of the device (para. [0069] and para. [0099]).
Regarding claim 7, Zenhausern discloses wherein the amplification reaction is by PCR;LCR; isothermal; and/or RCA (PCR primers are designed for a panel of genes, with target (s) amplified using standard PCR, para. [0236], lines 13-14).
Regarding claim 8, Zenhausern discloses wherein the MRR comprises a polymeric-based solution configured to interact with mucin in the liquid biological sample that comprises saliva (vertical flow detection devices may have a membrane that comprises one or more porous solid state materials, including polymers, para. [0015]), the device further comprising: a filter substrate material having an average pore size selected to remove debris and food residue from the saliva (porosity of membrane 3, decreasing the membrane 3 pore size is an effective way to increase the maximum flow 23 rate Q to allow more antigen 13 to be detected by the sensor, para. [0099]; membrane 3 pore size is equal or smaller than traditional LFI for better capturing efficiency, para. [0188], lines 12-13); and a substrate material having a physical parameter and chemical property configured to establish an interface with the biofluid sample for directing one or more analytes in the biofluid sample to the VFB (Both faster flow 23 and smaller pore size will increase the working pressure to flow sample through the paper membrane 3, para. [0190], lines 1-3).
Regarding claim 9, Zenhausern discloses wherein the VFB is an electromagnetic power-free VFB that is fluidically activated by intra-molecular or external forces (vertical flow detection device is compatible with a range of flow-driving components, such as a flow device that is a syringe, a pump, or a passive capillary driven system, para. [0022]), comprising: a membrane housing (holder 29, para. [0100], lines 4-5; external force—microgravity or gravity, para. [0271], line 3); and a sample absorbent pad in fluidic contact with the membrane (absorbent material 57, para. [0227], lines 6-7; there is an absorbent material 57, acting as a capillary pump to pull the sample through the detection membrane 3, para. [0228], lines 15-16), wherein the multiplex membrane and the sample absorbent pad are positioned in the membrane housing and the absorbent pad is fluidically connected to the liquid biological sample (the sample will be pre-filtered before going into the detection membrane 3. The pre-filter 56 can be external, or together with the sample tube/holder 59. There is an absorbent material 57, acting as a capillary pump to pull the sample through the detection membrane 3, para. [0228], lines 12-16), wherein biomarkers from the biological liquid sample are provided to the multiplex membrane (various vertical flow-oriented devices and systems for detecting biomarkers, para. [0005], lines 1-2; abstract lines 1-2).
Regarding claim 10, Zenhausern discloses wherein the VFB is in a stacked-pad configuration comprising: a buffer pad configured to store assay buffer; a sample absorbent pad; the multiplex membrane, such as a polyethersulfone membrane; a conjugation pad; a retarding pad; and a flow directing pad (using 3D structures, e.g. stacked membranes 169, para. [0320], lines 10-11; further, Zenhausern shows a stacked configuration in Fig. 2A).
Regarding claim 11, Zenhausern discloses an imager for optical detection of presence or absence of the plurality of biomarkers in the VFB, wherein the imager is optionally a magnifying lens and/or a portable reader (a detector to detect a target analyte in a fluid sample bound to the capture agent, para. [0008], lines 2-3; detector may comprise a imager, para. [0008], line 5; VFI is inherently suitable for multiplex biomarker detection, para. [0120], lines 4-5).
Regarding claim 12, Zenhausern discloses wherein the imager comprises a magnifying lens configured to optically align with at least one lens of a smart phone or a commercially-available ancillary configured to perform biomarker analysis (Device 1 Integration and software: data analysis software for imaging with smart phone device 51 camera 53, para. [0225], lines 7-8).
Regarding claim 13, Zenhausern discloses a point-of-care microfluidic cartridge for preparing proteins in the liquid biological sample for detection by the VFB (a user-centered VFP platform with automated sample preparation for nucleic acid biomarker detection for space missions, para. [0263], lines 2-3; the sample preparation cartridge and instrumentation hardware are designed, built and tested (iteratively) to optimize the process to provide as high a success rate as possible, para. [0275], lines 1-4; areas of requirements will include each of the constituent parts of the multiplex biomarkers panel and protocol , including sample preparation , stabilization/transportation, preparation, quantification/detection, and interpretation of the multiplex array images, and their incorporation into a fully integrated automated point-of-need (PON) system, para. [0273], lines 6-12).
Regarding claim 14, Zenhausern discloses wherein the biomarkers comprise one or more of: human antibodies to an infectious agent, such as human anti-SARS- COV2 antibodies; total IgM, IgC, IgA, or combinations thereof; inflammatory or stress response protein(s), such as CRP; SARS-CoV-2 N-gene; Human CDKN1A, DDB2 and MRPS5 gene; and/or a small molecule or other biomolecular species indicative of a disease condition or an environmental exposure (analysis of multiplex biomarkers from serum and environmental or lab-grown samples, para. [0274], lines 11-12; detection of CDKN1A, para. [0335], lines 2-3).
Regarding claim 15, Zenhausern discloses wherein biomarker detection is independent of device orientation and operable under zero-g conditions (A VFP platform design, including sample preparations for gene expression biomarker detection that can operate in microgravity environment for spaceflight health monitoring using a simple fingerprick, which is integrated into an automated sample preparation, processing, and monitoring system, para. [0271], lines 1-5; a human-centered design of a VFP platform working in microgravity environment for space mission, including integrated sample preparation modules for gene expression based health monitoring, para. [0260], lines 1-4).
Regarding claim 16, Zenhausern discloses wherein the multiplex membrane comprises biomarker detectors to detect: presence or absence of a virus; and presence or absence of a host immune response (A detection antibody can be used to detect the presence of a target nucleic acid sequence bound to the capture antibody, para. [0334], lines 13-15; any of the vertical flow detection devices may be configured for use with a target analyte that comprises one or more of: DNA, RNA, para. [0018]; detection of HIV p24 and hepatitis B virus, para. [0092], lines 16-17; monitoring immune response, para. [0181], line 6).
Regarding claim 17, Zenhausern discloses A method of detecting a biological parameter (provided are vertical flow detection devices and related methods, abstract, lines 1-2), the method comprising the steps of: providing the device of claim 1 (device of claim 1 discussed above) introducing the liquid biofluid sample to the sample inlet (including a flow through area is 10mm in diameter encapsulated in a stainless steel filter holder 29, Fig. 2A; para. [0095], lines 7-8; also, Fig. 2A shows a sample inlet configured to receive a liquid biofluid sample); removing debris in the liquid biological sample by the pre-processing module (A pre-filtration through 0.2 um Polyethersulfone (PES) membrane is preferred to remove any micro-particles and cellular components that might clog the VFI membrane 3, para. [0217], lines 9-12); introducing the pre-processed filtered liquid biofluid sample mixture to the multiplex membrane (VFI system of device 1 comprises a membrane 3, Fig. 2A); and optically detecting the one or more biomarkers that have interacted with the multiplex membrane, thereby detecting the biological parameter (a detector to detect a target analyte in a fluid sample bound to the capture agent, para. [0008], lines 2-3; detector may comprise a imager, para. [0008], line 5; VFI is inherently suitable for multiplex biomarker detection, para. [0120], lines 4-5).
Regarding claim 18, Zenhausern discloses wherein the removing step comprises: mixing the liquid biofluid sample with a MRR and filtering the mixed liquid biofluid sample and MRR to provide a filtered liquid biological sample (the sample will be pre-filtered before going into the detection membrane 3. The pre-filter 56 can be external, or together with the sample tube/holder, para. [0228], lines 12-14; it is a convenient dry master mix that allows efficient and accurate first - strand cDNA synthesis. As such, reconstitution is simple by adding PCR-grade water along with your RNA to master mix. This system thus facilitates potential integration into automated point-of-care platform for sample preparation, para. [0246], lines 1-8; also, Zenhausern discloses one of ordinary skill in the art will appreciate that starting materials, biological materials, reagents, synthetic methods, purification methods, analytical methods, assay methods, and biological methods other than those specifically exemplified can be employed in the practice of the invention, para. [0419], lines 1-5).
Regarding claim 19, Zenhausern discloses having a total method time of less than one hour (samples were processed with a flow 23 rate of 1.5 mL/min and 10 min assay time, para. [0117], lines 10-11; the VFI device 1 technology provides a simple, miniaturized, and rapid ( sample-to-answer time under 30 min, para. [0122], lines 5-6).
Regarding claim 20, Zenhausern discloses, wherein the biological parameter is one or more of: determination of a past infection event; current infection status; immunity status; donor compatibility; vaccine quality control; radiation biodosimetry; prediction of treatment efficacy; risk assessment of disease susceptibility; screening/detection: indication of the presence of the disease; assessment of disease aggressiveness for prognosis; monitoring of disease recurrence and therapeutic response; and/or pharmacological response, including drug efficacy, dose response, safety or genotype (VFI parameters were optimized in order to develop a POC assay with improved sensitivity and both simplex and multiplex detection capabilities of biothreat pathogens, para. [0093], lines 12-15).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LENORA A. ABEL whose telephone number is (571)272-8270. The examiner can normally be reached Monday-Friday 7:00am-4:00pm.
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/L.A.A./Examiner, Art Unit 1799
/MICHAEL L HOBBS/Primary Examiner, Art Unit 1799
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