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 05/29/2025 has been considered by the examiner.
Claim Objections
Claims 1-2, 13-14, and 23-26 are objected to because of the following informalities:
Claim 1, please amend “contacting a sample comprising one or more metabolites” to “contacting [[a]] the sample comprising one or more metabolites”; “separating the metabolites” to “separating the one or more metabolites”.
Claim 2, please amend “contacting a sample comprising one or more metabolites” to “contacting [[a]] the sample comprising one or more metabolites”; “separating the metabolites” to “separating the one or more metabolites”.
Claim 13, please amend “with microchip-based capillary electrophoresis (CE) platform” to “with a microchip-based capillary electrophoresis (CE) platform”; “indicative of a disease or disorder” to “indicative of [[a]] the disease or disorder” in lines 13-14.
Claim 14, please amend “with microchip-based capillary electrophoresis (CE) platform” to “with a microchip-based capillary electrophoresis (CE) platform”; “indicative of a disease or disorder” to “indicative of [[a]] the disease or disorder” in lines 14-15.
Claims 23-25, please amend “wherein the microchip” to “wherein the microchip of the microchip-based CE platform”.
Claim 26, please amend “adjusting the pH” to “adjusting [[the]] a pH”.
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 applicant regards as his invention.
Claims 13-19 and 21-26 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.
Regarding Claim 13, the limitation “the adensosine 5’ – triphosphate (ATP)” lacks antecedent basis. Claims 15-19 and 21-25 are further rejected by virtue of their dependence upon and because they fail to cure the deficiencies of indefinite claim 13.
Regarding Claim 14, the limitations “the therapeutic benefit” and “the ATP” lack antecedent basis.
Regarding Claim 23, Claim 23 contains the trademark/trade name “ZipChipTM”. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods 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, the trademark/trade name is used to identify/describe the microchip and associated separation instruments, including capillary electrophoresis and mass spectrometry, accordingly, the identification/description is indefinite.
Regarding Claim 26, the limitation “the background electrolyte” lacks antecedent basis.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 13-16, 18-19, and 21-22 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Farber (WO 2019/089740 A1, provided in IDS dated 05/29/2025).
Regarding Claim 13, Farber teaches a method of diagnosing a disease or disorder (method can be used to diagnose disease [page 62, lines 9-10; page 45, lines 15-31]) associated with aberrant nucleotide-dependent signaling in a subject (disease can be diagnosed via extracellular adenosine concentration [page 45, lines 15-31]), comprising:
(a) contacting a sample from the subject (sample may be a sample from a cancer subject [page 2, lines 17-27]) with microchip-based capillary electrophoresis (CE) platform (sample can be separated via on-chip capillary electrophoresis [page 39, lines 27-34]);
(b) separating adenosine 5’-triphosphate (ATP), ATP analogues and/or degradation products by molecular weight and/or charge in one or more capillaries using CE (separation of ionic molecules is done in CE [page 39, lines 29-31], metabolite may be ATP and degradation products such as adenosine [see Table 1 pages 12-14]); and
(c) eluting the ATP, ATP analogues and/or degradation products from the one or more capillaries (eluted sample can be used in a capillary electrophoresis-mass spectrometry system [page 42, lines 15-20]); and
(d) detecting the eluted ATP, ATP analogues and/or degradation products by mass spectrometry analysis (eluted sample can be detected using a capillary electrophoresis-mass spectrometry system [page 42, lines 15-20]);
wherein the microchip-based CE platform integrates electrophoretic separation and electrospray ionization into a mass spectrometer (capillary may interface into an electrospray [page 40, lines 2-3]; mass spectrometry system can be an ESI-MS system [page 42, lines 19-20]); and
wherein the presence of ATP, ATP analogues and/or degradation products is indicative of the disease or disorder associated with aberrant nucleotide-dependent signaling in the subject (disease can be diagnosed via extracellular adenosine concentration [page 45, lines 15-31]).
Regarding Claim 14, Farber teaches a method of monitoring a therapeutic benefit of a compound of a disease or disorder (method is used to identify or track biomarkers associated with, for instance, anti-immune checkpoint-based therapy [page 2, lines 7-16]) associated with aberrant nucleotide-dependent signaling in a subject treated with the compound (disease can be diagnosed via extracellular adenosine concentration [page 45, lines 15-31]), comprising:
(a) contacting a sample from the subject (sample may be a sample from a cancer subject [page 2, lines 17-27]) with microchip-based capillary electrophoresis (CE) platform (sample can be separated via on-chip capillary electrophoresis [page 39, lines 27-34]);
(b) separating adenosine 5’-triphosphate (ATP), ATP analogues and/or degradation products by molecular weight and/or charge in one or more capillaries using CE (separation of ionic molecules is done in CE [page 39, lines 29-31], metabolite may be ATP and degradation products such as adenosine [see Table 1 pages 12-14]); and
(c) eluting the ATP, ATP analogues and/or degradation products from the one or more capillaries (eluted sample can be used in a capillary electrophoresis-mass spectrometry system [page 42, lines 15-20]); and
(d) detecting the eluted ATP, ATP analogues and/or degradation products by mass spectrometry analysis (eluted sample can be detected using an capillary electrophoresis-mass spectrometry system [page 42, lines 15-20]);
wherein the microchip-based CE platform integrates electrophoretic separation and electrospray ionization into a mass spectrometer (capillary may interface into an electrospray [page 40, lines 2-3]; mass spectrometry system can be an ESI-MS system [page 42, lines 19-20]); and
wherein the presence of ATP, ATP analogues and/or degradation products is indicative of a disease or disorder associated with aberrant nucleotide-dependent signaling in the subject (disease can be diagnosed via extracellular adenosine concentration [page 45, lines 15-31]).
Regarding Claim 15, Farber teaches the method of claim 13.
Farber teaches wherein the disease or disorder is associated with increased levels of extracellular ATP (eATP) (extracellular adenosine from ATP is associated with various diseases [page 45, lines 15-31]).
Regarding Claim 16, Farber teaches the method of claim 13.
Farber teaches wherein the disease or disorder is a chronic inflammatory disease (disease of interest can be systemic lupus erythematosus [page 50, line 25]).
Regarding Claim 18, Farber teaches the method of claim 16.
Farber teaches wherein the chronic inflammatory disease is systemic lupus erythematosus (disease of interest can be systemic lupus erythematosus [page 50, line 25]).
Regarding Claim 19, Farber teaches the method of claim 13.
Farber teaches wherein the sample is a blood, plasma, or cell (sample can be whole blood, plasma, tissue sample [page 29, lines 25-31]).
Regarding Claim 21, Farber teaches the method of claim 13.
Farber teaches wherein the sample comprises a chelating agent (chelating agents, such as EDTA, can be used in the method [page 70, 22-28]).
Regarding Claim 22, Farber teaches the method of claim 21.
Farber teaches wherein the chelating agent is ethylenediaminetetraacetic acid (EDTA) (chelating agents, such as EDTA, can be used in the method [page 70, 22-28]).
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 1-9, 11-12, and 24-25 are rejected under 35 U.S.C. 103 as being unpatentable over Farber in view of Barron (The use of coated and uncoated capillaries for the electrophoretic separation of DNA in dilute polymer solutions. Electrophoresis 1995; 16, 64-74).
Regarding Claim 1, Farber teaches a method for detecting a metabolite of interest (a method for detecting metabolites [page 8, lines 3-6]) in a sample (sample can be blood [page 29, lines 25-26]), comprising:
(a) contacting a sample comprising one or more metabolites of interest (a sample containing at least one biomarker [page 29, lines 25-31]) with a capillary electrophoresis (CE) platform (sample can be separated using capillary electrophoresis [page 39, lines 27-29]);
(b) separating the metabolites by molecular weight and/or charge in one or more capillaries using CE (capillary electrophoresis is used to separate charged metabolites [page 40, lines 4-17]);
(c) eluting the metabolite from the one or more capillaries analysis (eluted sample can be used in a capillary electrophoresis-mass spectrometry system [page 42, lines 15-20]); and
(d) detecting the eluted metabolite by mass spectrometry analysis (eluted sample can be detected using a capillary electrophoresis-mass spectrometry system [page 42, lines 15-20]).
Farber is silent on wherein the CE platform uses an uncoated capillary.
Barron teaches separation of nucleotides using DNA fragments (abstract), and teaches wherein the CE platform uses an uncoated capillary (uncoated capillaries [Section 2.3.1 Uncoated capillaries, page 66] for separating DNA fragments of various length and charge [see Figure 1b on page 67]).
Farber and Barron are considered analogous art to the claimed invention because they are in the same field of method of separating charged metabolites. It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the capillary of the CE system of Farber to be uncoated, as taught by Barron, as using an uncoated capillary provides a longer runtime for better peak separation and resolution (Barron, [Conclusion, page 73]).
Regarding Claim 2, Farber teaches a method for detecting a metabolite of interest (a method for detecting metabolites [page 8, lines 3-6]) in a sample (sample can be blood [page 29, lines 25-26]), comprising:
(a) contacting a sample comprising one or more metabolites of interest (a sample containing at least one biomarker [page 29, lines 25-31]) with a capillary electrophoresis (CE) platform (separation of sample can be performed using capillary electrophoresis [page 39, lines 27-29]);
(b) separating the metabolites by molecular weight and/or charge in one or more capillaries using CE (capillary electrophoresis is used to separate charged metabolites [page 40, lines 4-17]);
(c) eluting the metabolite from the one or more capillaries analysis (eluted sample can be used in a capillary electrophoresis-mass spectrometry system [page 42, lines 15-20]); and
(d) detecting the eluted metabolite by mass spectrometry analysis (eluted sample can be detected using an capillary electrophoresis-mass spectrometry system [page 42, lines 15-20]).
Farber is silent on wherein the CE platform having a chemically-modified surface.
Barron teaches separation of nucleotides using DNA fragments (abstract), and teaches wherein the CE platform uses a chemically-modified surface (capillaries are coated with polyacrylamide [Section 2.3.2 Coated capillaries, pages 66-67] for separating DNA fragments of various length and charge [see Figure 1a on page 67]).
Farber and Barron are considered analogous art to the claimed invention because they are in the same field of method of separating charged metabolites. It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the capillary of the CE system of Farber to have a chemically-modified surface, as taught by Barron, as using coated capillary provides separation of analytes with a shorter runtime compared to some uncoated capillary setups (Barron, [see Figure 1a and 1b, page 68]).
Regarding Claim 3, modified Farber teaches the method of claim 1.
Farber teaches wherein the CE platform is a microchip-based system (capillary electrophoresis can be on-chip [page 39, lines 27-28]).
Regarding Claim 4, modified Farber teaches the method of claim 3.
Farber teaches wherein the microchip-based CE platform integrates electrophoretic separation and electrospray ionization (capillary may interface into an electrospray [page 40, lines 2-3]) into a mass spectrometer (mass spectrometry system can be an ESI-MS system [page 42, lines 19-20]).
Regarding Claim 5, modified Farber teaches the method of claim 1.
Farber teaches wherein the metabolite of interest is listed in Table 1 (metabolites separated may include adenosine, ADP, and ATP [see Table 1 pages 12-14]).
Regarding Claim 6, modified Farber teaches the method of claim 1.
Farber teaches wherein the metabolite of interest is an anionic metabolite (metabolite may be ATP [see Table 1 pages 12-14]).
Regarding Claim 7, modified Farber teaches the method of claim 1.
Farber teaches wherein the metabolite is a degradation product (metabolite may be adenosine [see Table 1 pages 12-14]).
Regarding Claim 8, modified Farber teaches the method of claim 1.
Farber teaches wherein the metabolite of interest is adenosine 5’-triphosphate (ATP) (metabolite may include ATP [see Table 1 pages 12-14]).
Regarding Claim 9, modified Farber teaches the method of claim 1.
Farber teaches wherein the sample is a blood, plasma, or cell (sample can be whole blood, plasma, tissue sample [page 29, lines 25-31]).
Regarding Claim 11, modified Farber teaches the method of claim 1.
Farber teaches wherein the sample comprises a chelating agent (chelating agents, such as EDTA, can be used in the method [page 70, 22-28]).
Regarding Claim 12, modified Farber teaches the method of claim 11.
Farber teaches wherein the chelating agent is ethylenediaminetetraacetic acid (EDTA) (chelating agents, such as EDTA, can be used in the method [page 70, 22-28]).
Regarding Claim 24, Farber teaches the method of claim 13.
Farber is silent on wherein the microchip comprises a chemically-modified surface.
Barron teaches separation of nucleotides using DNA fragments (abstract), and teaches wherein the microchip comprises a chemically-modified surface (capillaries are coated with polyacrylamide [Section 2.3.2 Coated capillaries, pages 66-67] for separating DNA fragments of various length and charge [see Figure 1a on page 67]).
Farber and Barron are considered analogous art to the claimed invention because they are in the same field of method of separating charged metabolites. It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the capillary of the CE system of Farber to have a chemically-modified surface, as taught by Barron, as using coated capillary provides a shorter runtime compared to some uncoated capillary setups (Barron, [see Figure 1a versus 1b, page 68]).
Regarding Claim 25, Farber teaches the method of claim 13.
Farber is silent on wherein the microchip does not comprise a surface modification.
Barron teaches separation of nucleotides using DNA fragments (abstract), and teaches wherein the microchip does not comprise a surface modification (uncoated capillaries [Section 2.3.1 Uncoated capillaries, page 66] for separating DNA fragments of various length and charge [see Figure 1b on page 67]).
Farber and Barron are considered analogous art to the claimed invention because they are in the same field of method of separating charged metabolites. It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the microchip CE system of Farber to not comprise a surface modification, as taught by Barron, as using an uncoated capillary provides a longer runtime for better peak separation (Barron, [Conclusion, page 73]).
Claims 17 are rejected under 35 U.S.C. 103 as being unpatentable over Farber, as applied to claim 16 above, and in view of Faruqi (Serum LDH in chronic cough: a potential marker of airway inflammation. The Clinical Respiratory Journal 2012; 81-87).
Regarding Claim 17, Farber teaches the method of claim 16.
Farber is silent on wherein the cough is chronic idiopathic cough.
Faruqi teaches measuring lactate dehydrogenase levels for patients with chronic cough (abstract), and teaches wherein the cough is chronic idiopathic cough (chronic cough associated with increased LDH levels and metabolites including pyruvate and lactate [third para. col 1., page 82; first para. col. 1, page 81]).
Faruqi and Farber are considered analogous art to the claimed invention because they are in the same field of method of measuring markers for diseases. It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the disease or disorder of Farber to be chronic idiopathic cough, as taught by Faruqi, as using targeting lactate and pyruvate have been linked to chronic cough (Faruqi, [Section of Introduction, page 81-82]).
Claim 23 is rejected under 35 U.S.C. 103 as being unpatentable over Farber, as applied to claim 13 above, and in view of Zipchip (Zipchip Sample Guide, 2021).
Regarding Claim 23, Farber teaches the method of claim 13.
Farber is silent on wherein the microchip is a ZipChip.
ZipChip Sample Guide teaches a Zipchip system to separate various sample types (abstract), and teaches wherein the microchip is a ZipChip (Zipchip system can be used to separate analytes, such as metabolites [first para. col. 1, page 1]).
Farber and ZipChip Sample Guide are considered analogous art to the claimed invention because they are in the same field of method of separating charged metabolites. It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the CE system of Farber to be a Zipchip, as taught by ZipChip Sample Guide, as using the Zipchip system allows for separation of metabolites (ZipChip Sample Guide, [first para. col. 1, page 1]).
Claim 26 is rejected under 35 U.S.C. 103 as being unpatentable over Farber and Barron, as applied to claim 1 above, and in view of ZipChip Sample Guide.
Regarding Claim 26, modified Farber teaches the method of claim 1.
further comprising adjusting a pH of a background electrolyte (BGE) relative to the metabolite of interest prior to mass spectrometry analysis.
ZipChip Sample Guide teaches further comprising adjusting a pH of the background electrolyte (BGE) relative to the metabolite of interest prior to mass spectrometry analysis (pH of BGE kit varied depending on analyte studied [first para. col. 1, page 1]; this adjustment would occur prior to mass spectrometry [third para. col. 1, page 2]).
It would be obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method of modified Farber to adjusting a pH of a background electrolyte (BGE) relative to the metabolite of interest prior to mass spectrometry analysis, as taught by ZipChip Sample Guide, as adjusting pH is important for a Zipchip system to be fully compatible with electrospray mass spec (ZipChip Sample Guide, [third para. col. 1, page 2]).
Conclusion
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/R.L.G./Examiner, Art Unit 1795
/SHIZHI QIAN/Primary Examiner, Art Unit 1795
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