DETAILED ACTION
In application filed on 06/14/2023, Claims 1, 4, 6, 7, 11, 12, 30, 32, 33, 45, 48, 52, 67-69, 72, 91, 93, 128, 138-141, 144, 145, 149, 150, 152, 158, 161, 176, 178, 200, 227-230, 233, and 241 are pending. The claim set submitted on 07/13/2026 is considered because this is the most recent claim set with some preliminary amendments. Claims 1, 4, 6, 7, 11, 12, 30, 32, 33, 45, 48, 52, 67-69, 72, 91, 93, 128, 138-141, 144, 152, and 262-267 are considered in the current office 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 03/21/2024 and 07/13/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Election/Restrictions
Applicant’s election without traverse of Group I in the reply filed on 07/13/2026 is acknowledged. Claims 117-125 and 128-130 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Groups, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 07/13/2026. In the election on 07/13/2026, Applicant has cancelled all non-elected Groups/claims. Claims 145, 149, 150, 158, 161, 176, 178, 200, 227-230, 233, and 241 are cancelled.
Group I, Claims 1, 4, 6, 7, 11, 12, 30, 32, 33, 45, 48, 52, 67-69, 72, 91, 93, 128, 138-141, 144, 152, and 262-267 are considered on the merits below.
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.
Claims 12, 33, 68, 138 and 152 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 12 recites the limitation "the inner surface material" in line 2 of the claim. There is insufficient antecedent basis for this limitation in the claim.
For the purpose of expedited prosecution, the limitation "the inner surface material" is interpreted by the Examiner as "an inner surface material".
Applicant should provide clarification.
Claim 33 recites the limitations " the range", “the mobile phase chaotropic agent” and “the pre-determined concentration”. There is insufficient antecedent basis for these limitations in the claim.
For the purpose of expedited prosecution, the limitations "the range", “the mobile phase chaotropic agent” and “the pre-determined concentration" are interpreted by the Examiner as " a range", “a mobile phase chaotropic agent” and “a pre-determined concentration”
Applicant should provide clarification.
Claim 68 recites the limitation " the use”. There is insufficient antecedent basis for these limitations in the claim.
For the purpose of expedited prosecution, the limitations "the use" is interpreted by the Examiner as "a use”
Applicant should provide clarification.
Claim 138 recites the limitation "the components”. There is insufficient antecedent basis for these limitations in the claim.
For the purpose of expedited prosecution, the limitations "the components” is interpreted by the Examiner as "a plurality of the component”
Applicant should provide clarification.
Claim 152 recites the limitation "the quantities”; “the plurality of the one or more biomolecules”; “the measured quantities”; and “the plurality of the one or more biomolecules in the test sample”. There is insufficient antecedent basis for these limitations in the claim.
For the purpose of expedited prosecution, the limitations "the quantities”; “ the plurality of the one or more biomolecules”; “the measured quantities”; and “the plurality of the one or more biomolecules in the test sample” is interpreted by the Examiner as "a quantities”; “ a plurality of the one or more biomolecules”; “a measured quantities”; and “a plurality of the one or more biomolecules in the test sample”.
Applicant should provide clarification.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 152 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. The claims have been analyzed for eligibility in accordance with their broadest reasonable interpretation. All claims are directed to statutory categories, i.e., a method (Claims 152) (Step 1: YES).
Analysis:
Claim 152: Ineligible.
Step 1:
The claim recites a series of steps or acts, including “identifying a signature comprising one or more identified biomolecules”. Thus, the claim is directed to a method, which is one of the statutory categories of invention (Step 1: YES).
Step 2A Prong 1:
Claim 1 recites “identifying a signature comprising one or more identified biomolecules, the identifying comprising: based on at least one of the one or more data sets, measuring the quantities of each of a plurality of the one or more biomolecules in the test sample; selecting a subset of the plurality of the one or more biomolecules in the sample based on the measured quantities; and determining the identities of each of the subset of the plurality of the one or more biomolecules in the test sample. (mental step)”.
Therefore, the claim is directed towards an abstract idea, and more specifically to the abstract idea group of a mental processes since claim 152 relates to using a mental process to “identify a signature comprising one or more identified biomolecules, the identifying comprising :…” (Step 2A, Prong 1: Patent Ineligible).
Step 2A, Prong 2:
This judicial exception is not integrated into a practical application.
Once the process of identifying is done, No further action takes place.
Also the steps of “ the method of claim 1” are recited at a high level of generality that it amounts to mere data gathering (insignificant extra-solution activity). See MPEP 2106.05(g).
Step 2B:
Furthermore, the courts have found that limitations adding insignificant extrasolution activity to the judicial exception, such as mere data gathering in conjunction with a law of nature or abstract idea, are limitations found not to be enough to qualify as ‘significantly more’ when recited in a claim with a judicial exception (see the 2014 Interim Guidance on Patent Subject Matter Eligibility of the Federal Register dated December 16, 2014; and MPEP 2106.05(I)(A)). Note that mere data gathering is not significantly more than the abstract idea. See MPEP 2106.05(g).
Here, there are no additional elements which are significantly more than the abstract idea. The steps of “the method of claim 1” appears to be well-understood, routine, and conventional (WURC) in the field of proteomics, as evidenced by Kaur et al. (US20170315132A1) in view of Jindal et al. (US20020150926A1) (Step 2B: NO).
Therefore, Claim 152 is ineligible.
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, 6, 11, 67-68, 72, 91, 93, 128, 138-141, 144, 152, 262 and 263 are rejected under 35 U.S.C. 103 as being unpatentable over by Kaur et al. (US20170315132A1) in view of Jindal et al. (US20020150926A1).
Regarding Claim 1, Kaur teaches a method for processing a test sample (See Para 0002… antibody-drug conjugates) for a mass spectrometry analysis (See Para 0002… methods of capturing, detecting, analyzing, characterizing, and quantifying antibody-drug conjugates, and their fragments and metabolites, in non-biological or biological matrices by mass spectrometry), the method comprising:
subjecting the test sample (referred to as ADC [Para 0008]) to a size-exclusion chromatography (SEC) technique using a SEC microfluidic device (See Para 0008… the ADC may be enriched, for example, by techniques such as size exclusion chromatography),
wherein the test sample (referred to as ADC [Para 0008]) comprises one or more biomolecules (referred to as an antibody-drug conjugate (ADC) [Para 0007-0008]) and a chaotropic agent (referred to as guanidine [Para 0127]; See Para 0127…The ADC is reduced by contact with a composition that includes at least one reductant, for example dithiolthreitol (DTT), 2-mercaptoethanol, or tris(2-carboxyethyl)phosphine (TCEP). The ADC may also be denatured by contact with a composition that includes at least one denaturant, for example formamide, dimethylformamide, acetonitrile, SDS, urea, guanidine), and
(b) collecting a plurality of fractions eluted from the SEC microfluidic device (See Para 0008…the ADC may be enriched, for example, by techniques such as size exclusion chromatography…Thus, the analysis methods of this disclosure may proceed with the ADC, or fragments thereof, bound to an affinity capture media, thereby teaching “collecting a plurality of fractions eluted from the SEC microfluidic device”);
(c) subjecting one or more of the plurality of fractions from the SEC microfluidic device to a proteolytic technique (See Para 0008…which may include optional washing and eluting steps to further purify or enrich the ADC, or ADC fragments, to be analyzed.; See Para 0009…analysis methods may also include dephosphorylating the ADC, reducing and/or denaturing the ADC, and enzymatically digesting the ADC. Enzymatic digestion of the ADC may be accomplished by contacting the antibody with a proteolytic enzyme, for example, trypsin, chymotrypsin, papain, pepsin, LysN, LysC, AspN, GluC, ArgC, PNGaseF, or combinations of such enzymes, thereby teaching “proteolytic technique” ); and
(d) individually subjecting one or more fractions from one or both of steps (b) and
(c) to a reversed-phase liquid chromatography (RPLC) technique (See Para 0008… the ADC may be enriched, for example, by techniques such as …liquid chromatography, reversed-phase chromatography; Examiner submits that RPLC technique is implicitly taught) using a RPLC microfluidic device (See Para 0129… a liquid chromatography support; See Para 0008…reversed-phase chromatography; Examiner submits that RPLC microfluidic device is implicitly taught) under conditions to prepare a component of each of the one or more fractions for introduction to a mass spectrometer (See Para 0010… The analysis of the digested antibody-drug conjugate peptide mixture may be conducted by LC-MS/NIS, and such analysis may include detecting one peptide fragment from the digested ADC).
While Kaur implicitly teaches reversed-phase liquid chromatography (RPLC) technique and RPLC microfluidic device,
Kaur does not explicitly teach:
a reversed-phase liquid chromatography (RPLC) technique using a RPLC microfluidic device
wherein the SEC microfluidic device comprises a plurality of interconnected channels;
wherein the RPLC microfluidic device comprises a plurality of interconnected channels comprising a reversed-phase medium, and
wherein the RPLC microfluidic device is coupled to an electrospray ionization source.
In the analogous art of novel methods for screening a sample to select a ligand to a target of interest and for obtaining information about the ligand and its binding characteristics, Jindal teaches:
a reversed-phase liquid chromatography (RPLC) technique (See Para 0208…by conventional reversed phase chromatographic techniques under acid conditions) using a RPLC microfluidic device (referred to as reversed phase columns [Para 0095]);
wherein the SEC microfluidic device (referred to as size exclusion columns [Para 0095]) comprises a plurality of interconnected channels (See Para 0122…the pores of the SEC matrix);
wherein the RPLC microfluidic device (referred to as reversed phase columns [Para 0095]) comprises a plurality of interconnected channels (See Para 0198… a POROSI R2 reversed-phase column; Examiner submits that a POROSI R2 reversed-phase column has pores ) comprising a reversed-phase medium (See Para 0198…a POROSI R2 reversed-phase column (2.1×100 mm; See Para 0088…These “restricted access media, have been particularly useful in the separation of low molecular weight drugs in serum from proteins. The first of these columns was the “internal surface reversed phase” (ISRP) media. Another RAM type phase is the “semipermeable surface, “media”); Examiner submits under BRI that a POROSI R2 reversed-phase column has a plurality of interconnected channels comprising a reversed-phase medium, as evidenced by ThermoFisher), and
wherein the RPLC microfluidic device (referred to as reversed phase columns [Para 0095]) is coupled to an electrospray ionization source (See Para 0104…The integrated coupling of various dimensions … with capillary reverse phase HPLC/electrospray ionization mass spectrometry in an automated multidimensional system).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified a method of Kaur to include that “wherein the SEC microfluidic device comprises a plurality of interconnected channels; wherein the RPLC microfluidic device comprises a plurality of interconnected channels comprising a reversed-phase medium, and wherein the RPLC microfluidic device is coupled to an electrospray ionization source”, as taught by Jindal for the benefit of providing a multi-target column format can be used to screen ligands for their ability to bind to a certain target and for their inability to bind to a second target in a single process (Jindal, Para 0200), allowing for the provision for an integrated, multi-dimensional screening, selection and analysis systems and methods which permit automated, direct transfer of samples without dilution or loss between various dimensions, and efficiently screen for, and subsequently permit characterization and recovery of ligands to a target of interest, even when present at low concentration (Jindal, Para 0010).
Regarding Claim 6, the method of claim 1 is obvious over Kaur in view of Jindal.
Kaur teaches that the chaotropic agent (See Page 127… guanidine; See Claim 1… guanidine HCl) is guanidine hydrochloride or guanidinium chloride (See Page 127… guanidine; See Claim 1… guanidine HCl).
Regarding Claim 11, the method of claim 1 is obvious over Kaur in view of Jindal.
Kaur does not teach that the test sample subjected to the SEC technique using the SEC microfluidic device has a volume of about 1 µL to about 200 µL.
In the analogous art of the analogous art of novel methods for screening a sample to select a ligand to a target of interest and for obtaining information about the ligand and its binding characteristics, Jindal teaches that the test sample (referred to a target or receptor and sample [Para 0122]) subjected to the SEC technique (See Para 0122…he first dimension, a size exclusion chromatography system, is very similar to a dialysis system ) using the SEC microfluidic device (referred to as size exclusion columns [Para 0095, 0122]) has a volume (See Para 0139…SEC column as a volume, under BRI).
Regarding the volume of about “1 µL to about 200 µL”, MPEP § 2144.05, Part II, Subpart B holds that a particular parameter that is recognized as a result effective variable (“a variable that achieves a recognized result”) would be one, but not the only motivation for a person of ordinary skill in the art to experiment to reach another workable product or process. In the design and fabrication of SEC columns, the total volume of a Size Exclusion Chromatography (SEC) column directly determines sample load capacity, resolution, and elution times.Thus, the SEC microfluidic device having a volume of about 1 µL to about 200 µL is a result effective variable.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified a method of Kaur to include that that the test sample subjected to the SEC technique using the SEC microfluidic device has a volume of about 1 µL to about 200 µL”, as taught by Jindal for the benefit of providing a multi-target column format can be used to screen ligands for their ability to bind to a certain target and for their inability to bind to a second target in a single process (Jindal, Para 0200), allowing for the provision for an integrated, multi-dimensional screening, selection and analysis systems and methods which permit automated, direct transfer of samples without dilution or loss between various dimensions, and efficiently screen for, and subsequently permit characterization and recovery of ligands to a target of interest, even when present at low concentration (Jindal, Para 0010).
Regarding Claim 67, the method of claim 1 is obvious over Kaur in view of Jindal.
Kaur teaches that the proteolytic technique (See Para 0008…which may include optional washing and eluting steps to further purify or enrich the ADC, or ADC fragments, to be analyzed.; See Para 0009…these analysis methods may also include dephosphorylating the ADC, reducing and/or denaturing the ADC, and enzymatically digesting the ADC. Enzymatic digestion of the ADC may be accomplished by contacting the antibody with a proteolytic enzyme, for example, trypsin, chymotrypsin, papain, pepsin, LysN, LysC, AspN, GluC, ArgC, PNGaseF, or combinations of such enzymes, thereby teaching “proteolytic technique” ) comprises an enzyme-based digestion technique (See Para 0008…which may include optional washing and eluting steps to further purify or enrich the ADC, or ADC fragments, to be analyzed.; See Para 0009…these analysis methods may also include dephosphorylating the ADC, reducing and/or denaturing the ADC, and enzymatically digesting the ADC. Enzymatic digestion of the ADC may be accomplished by contacting the antibody with a proteolytic enzyme, for example, trypsin, chymotrypsin, papain, pepsin, LysN, LysC, AspN, GluC, ArgC, PNGaseF, or combinations of such enzymes, thereby teaching “proteolytic technique” hereby teaching “an enzyme-based digestion technique”).
Regarding Claim 68, the method of claim 1 is obvious over Kaur in view of Jindal.
Kaur teaches that the enzyme-based digestion technique (See Para 0008…which may include optional washing and eluting steps to further purify or enrich the ADC, or ADC fragments, to be analyzed.; See Para 0009…these analysis methods may also include dephosphorylating the ADC, reducing and/or denaturing the ADC, and enzymatically digesting the ADC. Enzymatic digestion of the ADC may be accomplished by contacting the antibody with a proteolytic enzyme, for example, trypsin, chymotrypsin, papain, pepsin, LysN, LysC, AspN, GluC, ArgC, PNGaseF, or combinations of such enzymes, thereby teaching “proteolytic technique” hereby teaching “an enzyme-based digestion technique”) comprises the use of an enzyme selected from the group consisting of trypsin, chymotrypsin,pepsin, LysC, LysN, AspN, GluC and ArgC, or a combination thereof (See Para 0009… Enzymatic digestion of the ADC may be accomplished by contacting the antibody with a proteolytic enzyme, for example, trypsin, chymotrypsin, papain, pepsin, LysN, LysC, AspN, GluC, ArgC, PNGaseF, or combinations of such enzymes, thereby teaching “proteolytic technique” hereby teaching “an enzyme-based digestion technique”).
Regarding Claim 72, the method of claim 67 is obvious over Kaur in view of Jindal.
Kaur teaches that the enzyme-based digestion technique (See Para 0009… Enzymatic digestion of the ADC may be accomplished by contacting the antibody with a proteolytic enzyme, for example, trypsin, chymotrypsin, papain, pepsin, LysN, LysC, AspN, GluC, ArgC, PNGaseF, or combinations of such enzymes, thereby teaching “proteolytic technique” hereby teaching “an enzyme-based digestion technique”) does not comprise a buffer exchange step (See Para 0009… Enzymatic digestion of the ADC may be accomplished by contacting the antibody with a proteolytic enzyme, for example, trypsin, chymotrypsin, papain, pepsin, LysN, LysC, AspN, GluC, ArgC, PNGaseF, or combinations of such enzymes, thereby teaching “proteolytic technique; Examiner submits under BRI that Kaur does not disclose “a buffer exchange step). Examiner submits that “, an alkylation step, and/or a reduction step” are optional and thus not required by the claim.
Regarding Claim 91, the method of claim 1 is obvious over Kaur in view of Jindal.
Kaur does not teach that the reversed-phased medium comprises a RPLC moiety mixture comprising two or more of the following alkyl moieties:C2, C4,C8, and C18.
In the analogous art of novel methods for screening a sample to select a ligand to a target of interest and for obtaining information about the ligand and its binding characteristics, Jindal teaches that the reversed-phased medium (See Para 0198…a POROSI R2 reversed-phase column (2.1×100 mm; See Para 0088…These “restricted access media, have been particularly useful in the separation of low molecular weight drugs in serum from proteins. The first of these columns was the “internal surface reversed phase” (ISRP) media. Another RAM type phase is the “semipermeable surface, “media”); comprises a RPLC moiety mixture (See Para 0183… vydac reversed phase C-18 ) comprising two or more of the following alkyl moieties:C2, C4,C8, and C18.(See Para 0183… vydac reversed phase C-18 column ).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified a method of Kaur to include that “the reversed-phased medium comprises a RPLC moiety mixture comprising two or more of the following alkyl moieties:C2, C4,C8, and C18”, as taught by Jindal for the benefit of providing a multi-target column format can be used to screen ligands for their ability to bind to a certain target and for their inability to bind to a second target in a single process (Jindal, Para 0200), allowing for the provision for an integrated, multi-dimensional screening, selection and analysis systems and methods which permit automated, direct transfer of samples without dilution or loss between various dimensions, and efficiently screen for, and subsequently permit characterization and recovery of ligands to a target of interest, even when present at low concentration (Jindal, Para 0010).
Regarding Claim 93, the method of claim 91 is obvious over Kaur in view of Jindal.
Kaur does not teach that the RPLC moiety mixture comprises the following alkyl moieties: C2, C4, C8, and C18.
In the analogous art of novel methods for screening a sample to select a ligand to a target of interest and for obtaining information about the ligand and its binding characteristics, Jindal teaches that the RPLC moiety mixture (See Para 0183…vydac reversed phase C-18 column) comprises the following alkyl moieties: C2, C4,C8, and C18 (See Para 0183…vydac reversed phase C-18 column).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified a method of Kaur to include that the RPLC moiety mixture comprises the following alkyl moieties: C2, C4,C8, and C18, as taught by Jindal for the benefit of providing a multi-target column format can be used to screen ligands for their ability to bind to a certain target and for their inability to bind to a second target in a single process (Jindal, Para 0200), allowing for the provision for an integrated, multi-dimensional screening, selection and analysis systems and methods which permit automated, direct transfer of samples without dilution or loss between various dimensions, and efficiently screen for, and subsequently permit characterization and recovery of ligands to a target of interest, even when present at low concentration (Jindal, Para 0010).
Regarding Claim 128, the method of claim 1 is obvious over Kaur in view of Jindal.
Kaur teaches that the sample from the individual is a blood sample (See Para 0008… In these methods, the ADC to be analyzed directly in the matrix that it may be found in, such as a buffer, whole blood), the method further comprises preparing a plasma sample (See Para 0133… cynomolgus monkey plasma) by subjecting the blood sample (Under BRI, Examiner submits that plasma is obtained from blood) to a plasma generation technique (See Para 0133… cynomolgus monkey plasma from commercial source, thereby teaching “a plasma generation technique”).
Regarding Claim 138, the method of claim 1 is obvious over Kaur in view of Jindal.
Kaur teaches subjecting the components, or products thereof, eluted (See Para 0005…Liquid chromatography-tandem mass spectrometry is a powerful tool for protein analysis and quantitation in very complex matrices like plasma/serum/tissue samples) from the RPLC microfluidic device (See Para 0129… a liquid chromatography support; See Para 0008…reversed-phase chromatography) to the mass spectrometer (See Para 0141…The reduced and digested samples were then analyzed by LC-MS/MS (Shimadzu LC, AB SCIEX 5500 QTrap mass spectrometers)).
Regarding Claim 139, the method of claim 1 is obvious over Kaur in view of Jindal.
Kaur teaches performing a mass spectrometry analysis of the components, or products thereof, of the sample (See Para 0005…Liquid chromatography-tandem mass spectrometry is a powerful tool for protein analysis and quantitation in very complex matrices like plasma/serum/tissue samples) using the mass spectrometer (See Para 0141…The reduced and digested samples were then analyzed by LC-MS/MS (Shimadzu LC, AB SCIEX 5500 QTrap mass spectrometers)).
Regarding Claim 140, the method of claim 139 is obvious over Kaur in view of Jindal.
Kaur teaches that the mass spectrometry analysis (See Para 0141…The reduced and digested samples were then analyzed by LC-MS/MS (Shimadzu LC, AB SCIEX 5500 QTrap mass spectrometers)) comprises an analysis of each fraction subjected to the RPLC technique (See Para 0008… the ADC may be enriched, for example, by techniques such as …liquid chromatography, reversed-phase chromatography) using the RPLC microfluidic device (See Para 0129… a liquid chromatography support; See Para 0008…reversed-phase chromatography) (See Para 0010… The analysis of the digested antibody-drug conjugate peptide mixture may be conducted by LC-MS/NIS, and such analysis may include detecting one peptide fragment from the digested ADC).
Regarding Claim 141, the method of claim 139 is obvious over Kaur in view of Jindal.
Kaur teaches that the mass spectrometry analysis (See Para 0141…The reduced and digested samples were then analyzed by LC-MS/MS (Shimadzu LC, AB SCIEX 5500 QTrap mass spectrometers)) comprises obtaining one or more data sets comprising information (See Para 0142…Table 2A and Table 2B…comparison of data) obtained from the mass spectrometer (See Para 0141…The reduced and digested samples were then analyzed by LC-MS/MS (Shimadzu LC, AB SCIEX 5500 QTrap mass spectrometers)) for each fraction subjected to the RPLC technique (See Para 0008… the ADC may be enriched, for example, by techniques such as …liquid chromatography, reversed-phase chromatography) using the RPLC microfluidic device (See Para 0129… a liquid chromatography support; See Para 0008…reversed-phase chromatography) (See Para 0010… The analysis of the digested antibody-drug conjugate peptide mixture may be conducted by LC-MS/NIS, and such analysis may include detecting one peptide fragment from the digested ADC).
Regarding Claim 144, the method of claim 1 is obvious over Kaur in view of Jindal.
Kaur teaches that a collection of compositions (See Para 0127… Such compositions may include additional solvents, buffers and/or pH modifying agents, such as acetonitrile, methanol, ethanol, HCl, ammonium bicarbonate, ammonium acetate, and/or formic acid, dephosphorylating agents including phosphatases such as calf intestinal alkaline phosphatase, bovine intestinal alkaline phosphatase, or lambda protein phosphatase) obtained from any one of the methods of claim 1 (See Claim 1 rejection) , wherein each composition of the collection of compositions (See Para 0127… Such compositions may include additional solvents, buffers and/or pH modifying agents, such as acetonitrile, methanol, ethanol, HCl, ammonium bicarbonate, ammonium acetate, and/or formic acid, dephosphorylating agents including phosphatases such as calf intestinal alkaline phosphatase, bovine intestinal alkaline phosphatase, or lambda protein phosphatase) is a RPLC microfluidic device eluate (See Para 0005…Liquid chromatography-tandem mass spectrometry is a powerful tool for protein analysis and quantitation in very complex matrices like plasma/serum/tissue samples; See Para 0119…The single analysis sample comprising both the drug and the digested antibody components is then analyzed by liquid chromatography—tandem mass spectrometry (LC-MS/MS) to detect and quantify both the drug and antibody component of the ADC, thereby teaching “a RPLC microfluidic device eluate”).
Regarding Claim 152, the method of claim 139 is obvious over Kaur in view of Jindal.
Kaur teaches further comprising identifying a signature comprising one or more identified biomolecules (See Para 0007…the digested drug and peptide mixture in the single analysis sample may then be analyzed by C-MS/MS to detect at least one signature peptide from the antibody and a drug), the identifying (See Para 0007…the digested drug and peptide mixture in the single analysis sample may then be analyzed by C-MS/MS to detect at least one signature peptide from the antibody and a drug) comprising:
based on at least one of the one or more data sets, measuring the quantities of each of a plurality of the one or more biomolecules in the test sample (See Para 0011…these analysis methods may determine the total antibody concentration of the antibody-drug conjugate, antibody-conjugated drug concentration of the ADC, and/or the average drug-to-antibody ratio (DAR) of the ADC.) ;
selecting a subset of the plurality of the one or more biomolecules in the sample based on the measured quantities (See Para 0067…Variants may be screened to determine whether they contain the desired properties; See Para 0113…The antibody components of an ADC may be identified, screened for, or characterized for their physical/chemical properties and/or biological activities by various assays known in the art.); and
determining the identities of each of the subset of the plurality of the one or more biomolecules in the test sample (See Para 0113…the antibody components of an ADC may be identified, screened for, or characterized for their physical/chemical properties and/or biological activities by various assays known in the art; See Para 0067…A useful method for identification of residues or regions of an antibody that may be targeted for mutagenesis is called “alanine scanning mutagenesis” as described by Cunningham and Wells (1989) Science, 244:1081-1085. ).
Regarding Claim 262, the method of claim 1 is obvious over Kaur in view of Jindal.
Kaur teaches that the chaotropic agent (referred to as guanidine [Para 0127]; See Para 0127…The ADC is reduced by contact with a composition that includes at least one reductant, for example dithiolthreitol (DTT), 2-mercaptoethanol, or tris(2-carboxyethyl)phosphine (TCEP). The ADC may also be denatured by contact with a composition that includes at least one denaturant, for example formamide, dimethylformamide, acetonitrile, SDS, urea, guanidine)comprises guanidine or a salt thereof, guanidinium or a salt thereof, potassium or a salt thereof, lithium or a salt thereof, magnesium or a salt thereof, or sodium or a salt thereof (referred to as guanidine [Para 0127]; See Para 0127…The ADC is reduced by contact with a composition that includes at least one reductant, for example dithiolthreitol (DTT), 2-mercaptoethanol, or tris(2-carboxyethyl)phosphine (TCEP). The ADC may also be denatured by contact with a composition that includes at least one denaturant, for example formamide, dimethylformamide, acetonitrile, SDS, urea, guanidine).
Regarding Claim 263, the method of claim 1 is obvious over Kaur in view of Jindal.
The combination of Kaur and Jindal does not teach that the plurality of interconnected channels each comprise a SEC medium.
In the analogous art of novel methods for screening a sample to select a ligand to a target of interest and for obtaining information about the ligand and its binding characteristics, Jindal teaches that the plurality of interconnected channels (See Para 0122…the pores of the SEC matrix) each comprise a SEC medium (See Para 0122… SEC matrix).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified a method of Kaur to include that “that the plurality of interconnected channels each comprise a SEC medium”, as taught by Jindal for the benefit of providing a multi-target column format can be used to screen ligands for their ability to bind to a certain target and for their inability to bind to a second target in a single process (Jindal, Para 0200), allowing for the provision for an integrated, multi-dimensional screening, selection and analysis systems and methods which permit automated, direct transfer of samples without dilution or loss between various dimensions, and efficiently screen for, and subsequently permit characterization and recovery of ligands to a target of interest, even when present at low concentration (Jindal, Para 0010).
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Kaur et al. (US20170315132A1) in view of Jindal et al. (US20020150926A1) as applied to claim 1 above, and further in view of Alaedini (US20150276757A1).
Regarding Claim 4, the method of claim 1 is obvious over Kaur in view of Jindal.
Kaur teaches wherein the test sample (See Para 0002… antibody-drug conjugates) has a concentration of the chaotropic agent (referred to as guanidine [Para 0127]; See Para 0127…The ADC is reduced by contact with a composition that includes at least one reductant, for example dithiolthreitol (DTT), 2-mercaptoethanol, or tris(2-carboxyethyl)phosphine (TCEP). The ADC may also be denatured by contact with a composition that includes at least one denaturant, for example formamide, dimethylformamide, acetonitrile, SDS, urea, guanidine).
The combination of Kaur and Jindal does not explicitly teach that the test sample has a concentration of the chaotropic agent of about 5 M to about 8 M.
In the analogous art of an invention pertains to the preparation of arrays containing the proteome of wheat, including gluten and non-gluten proteins, Alaedini teaches that the test sample (referred to as Gluten [Para 0091]) has a concentration of the chaotropic agent of about 5 M to about 8 M (See Para 0091… Fractions are dissolved in 6 M guanidine HCl (pH 8.0), containing 50 mM DTT).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified a method of Kaur and Jindal to include that the test sample has a concentration of the chaotropic agent of about 5 M to about 8 M, as taught by Alaedini, for the benefit of determining the molecular specificity of anti-gluten antibody reactivity (Alaedini, Para 0090), allowing for the provision of a systematic approach to characterize the molecular specificity of the immune response to wheat proteins in various diseases, thereby generating data that can be utilized to understand the disease mechanism and identify novel biomarkers for the diseases (Alaedini, Para 0007).
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Kaur et al. (US20170315132A1) in view of Jindal et al. (US20020150926A1) as applied to claim 1 above, and further in view of Hewitt et al. (US20200041389A1).
Regarding Claim 7, the method of claim 1 is obvious over Kaur in view of Jindal.
Kaur teaches wherein the chaotropic agent (See Page 127… guanidine; See Claim 1… guanidine HCl) in the test sample (See Para 0002… antibody-drug conjugates).
The combination of Kaur and Jindal does not teach that the chaotropic agent is from a liquid fixative.
In the analogous art of compositions for fixing tissue for cytologic, histomorphologic, and/or molecular analysis (e.g., DNA, RNA, and/or protein analysis), Hewitt teaches that the chaotropic agent (See Claim 23… The fixative of claim 23, wherein the guanidinium salt is selected from guanidinium thiocyanate, guanidinium HCL or guanidinium acetate) is from a liquid fixative (See Para 0006…Particular disclosed compositions (also referred to herein as “fixatives” or “fixative solutions”) include buffered ethanol.)
Hewitt further teaches that the disclosed fixatives include at least one component selected from ethanol, PBS, glycerol and glacial acetic acid and one or more additional components. In some examples, the additional components include a chaotrope or denaturant (for example, guanidinium thiocyanate, guanidinium HCl, or guanidinium acetate) (Para 0007).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified a method of Kaur and Jindal to include that that the chaotropic agent is from a liquid fixative, as taught by Hewitt for the benefit of developing compositions for fixing tissue for cytologic, histologic, flow cytometry applications and/or molecular analysis (e.g., DNA, RNA, and/or protein analysis) (Hewitt, Para 0006), allowing for the development of develop fixatives that improve quality of molecular analysis, particularly analysis of RNA, obtained from fixed samples. In addition, there is substantial interest in reducing or eliminating the use of formaldehyde, due to its health and environmental risks, as well as associated costs and difficulties in disposing of solutions containing formaldehyde (Hewitt, Para 0005).
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Kaur et al. (US20170315132A1) in view of Jindal et al. (US20020150926A1) as applied to claim 1 above, and further in view of Hirowatari et al. (US20120058549A1).
Regarding Claim 12, the method of claim 1 is obvious over Kaur in view of Jindal.
The combination of Kaur and Jindal does not teach that the range of the concentration of the mobile phase chaotropic agent of the SEC technique is within about +/- 40% of the pre- determined concentration of the chaotropic agent of the test sample.
In the analogous art of The present invention relates to a method of analyzing vitamin E such as α-tocopherol or γ-tocopherol contained in lipoproteins (high density lipoprotein/HDL, low density lipoprotein/LDL, intermediate density lipoprotein/IDL, very low density lipoprotein/VLDL, chylomicron/CM etc.) in a sample, and an analytical apparatus that can be used in such an analysis, Hirowatari teaches that the concentration of the mobile phase chaotropic agent of the SEC technique (See Para 0107… When a high concentration of caotropic ion (300 mmol/L or higher in the case of a perchlorate ion or a thiocyanate ion) is added to the eluant, the higher structure of the apoprotein may completely be destroyed resulting in the destruction of the structure of the lipoprotein as well, and thus may cause troubles in the separation of each lipoprotein by an ion exchange chromatography) is within % of the pre- determined concentration of the chaotropic agent of the test sample (See Para 0022… (3) The analytical method according to (1) or (2) wherein the pretreating solution further comprises 50-150 mmol/L of a caotropic ion at the step of reacting with the lipoprotein separated by the ion exchange chromatography)
Regarding the range of about “+/- 40%”, MPEP § 2144.05, Part II, Subpart B holds that a particular parameter that is recognized as a result effective variable (“a variable that achieves a recognized result”) would be one, but not the only motivation for a person of ordinary skill in the art to experiment to reach another workable product or process. In the use of size exclusion chromatography, changing the concentration of chaotropic agents (like guanidine hydrochloride or urea) in size exclusion chromatography (SEC) directly controls protein unfolding, subunit dissociation, and hydrodynamic volume, which alters retention times and prevents unwanted secondary interactions with the column matrix. Thus, the he range of the concentration of the mobile phase chaotropic agent of the SEC technique is within about +/- 40% of the pre- determined concentration of the chaotropic agent of the test sample is a result effective variable.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified a method of Kaur and Jindal to include that the range of the concentration of the mobile phase chaotropic agent of the SEC technique is within about +/- 40% of the pre- determined concentration of the chaotropic agent of the test sample, as taught by Hirowatari for the benefit of using an optimal amount of a caotropic ion in chromatography (Hirowatari, Para 0106), allowing for the provision a method of analyzing vitamin E in lipoproteins that permits the qualitative and quantitative measurement of vitamin Es in a process which is simplified to the extent amenable to automatic analysis, and an analytical apparatus that enables to automatically carry out said analytical method. (Hirowatari, Para 0018).
Claim 30 is rejected under 35 U.S.C. 103 as being unpatentable over Kaur et al. (US20170315132A1) in view of Jindal et al. (US20020150926A1) as applied to claim 1 above, and further in view of Kondo et al. (US20190204278A1).
Regarding Claim 30, the method of claim 1 is obvious over Kaur in view of Jindal.
The combination of Kaur and Jindal does not teach that the SEC microfluidic device comprises a SEC medium having an average pore size of about 10 nm to about 500 nm.
In the analogous art of a liquid chromatography packing material employing crosslinked polymer particles, wherein the volume average particle size of the crosslinked polymer particles is at least 2 μm but not more than 10 μm, the amount of fine particles having a particle size of 1 μm or less among the crosslinked polymer particles is less than 1% by volume, and the identity coefficient in the particle size distribution is not more than 1.15, Kondo teaches that the SEC microfluidic device (See Para 0013… a liquid chromatography packed column, and particularly a size exclusion chromatography packed column) comprises a SEC medium (See Para 0054… the liquid chromatography packing material of the present invention is used in size exclusion chromatography) having an average pore size of about 10 nm to about 500 nm (See Para 0055… but the average pore size is preferably at least 1 nm but not more than 60 nm; See Para 0088… and an average pore size of 50 nm.).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified a method of Kaur and Jindal to include that the SEC microfluidic device comprises a SEC medium having an average pore size of about 10 nm to about 500 nm, as taught by Kondo for the benefit of influencing the separation of the polymer sample (Kondo, Para 0054), allowing for providing a liquid chromatography packing material, and particularly a size exclusion chromatography packing material, which uses crosslinked polymer particles that combine the features of crosslinked polymer packing materials, including a broad molecular weight measurement range, favorable chemical stability and a high number of theoretical plates, and also enable high-speed analysis, as well as providing a liquid chromatography packed column, and particularly a size exclusion chromatography packed column, and a liquid chromatography analysis method (Kondo, Para 0013).
Claim 32 is rejected under 35 U.S.C. 103 as being unpatentable over Kaur et al. (US20170315132A1) in view of Jindal et al. (US20020150926A1) and further in view of Kondo et al. (US20190204278A1) as applied to claim 30 above, and further in view of Spaid et al. (US20070154895A1).
Regarding Claim 32, the method of claim 30 is obvious over Kaur in view of Jindal and further in view of Kondo.
The combination of Kaur Jindal and Kondo does not teach that the SEC medium is an inner surface of each of the plurality of interconnected channels.
In the analogous art of systems and methods of running multiple different analyses on a microfluidic device, Spaid teaches that the SEC medium (See Para 0045… Selective media can be those known in the art, such as, e.g., size selective media (e.g., size exclusion media or electrophoresis gels); See Para 0023… A reagent can be a selective (e.g., chromatographic) media in a reaction channel of the multi-assay microfluidic systems of the invention) is an inner surface (See Para 0034; Fig. 1… the reagents in reaction channels 107) of each of the plurality of interconnected channels (See Para 0045…reaction channels can include reagents in the form of selective media).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified a method of Kaur Jindal and Kondo to include that the SEC medium is an inner surface of each of the plurality of interconnected channels, as taught by Spaid for the benefit of providing a resultant signal via the interaction of the sample analytes with the reagent (Spaid, Para 0023), allowing for the provision of a way to quickly run multiple different analyses on low volume samples. It would be desirable to have a way to quickly and inexpensively screen large numbers of samples with multiple analyses to develop more reliable marker thresholds, and marker pattern correlations so that more asymptomatic cancers can be confidently identified (Spaid, Para 0006).
Claims 33, 45, 48 and 264-267 are rejected under 35 U.S.C. 103 as being unpatentable over Kaur et al. (US20170315132A1) in view of Jindal et al. (US20020150926A1) as applied to claim 1 above, and further in view of Spaid et al. (US20070154895A1).
Regarding Claim 33, the method of claim 1 is obvious over Kaur in view of Jindal.
The combination of Kaur and Jindal does not teach that the inner surface material of the plurality of interconnected channels of the SEC microfluidic device has a thickness of about 0.5 µm to about 2 µm.
In the analogous art of systems and methods of running multiple different analyses on a microfluidic device, Spaid teaches that the inner surface material (See Para 0045… a size exclusion media reagent) of the plurality of interconnected channels (See Para 0045…reaction channels can include reagents in the form of selective media) of the SEC microfluidic device (referred to as microfluidic device [Fig. 1, ref. 103; Para 0034]) has a thickness (See Para 0100… Proportioning and flow rates of solutions are controlled for each assay, e.g., by channel design and independent control of forces driving flows in each assay channel. The flow rate through each channel is affected by the resistance offered, e.g., by channel length, cross section, and geometry.)
Regarding the “a thickness of about 0.5 µm to about 2 µm”, MPEP § 2144.05, Part II, Subpart B holds that a particular parameter that is recognized as a result effective variable (“a variable that achieves a recognized result”) would be one, but not the only motivation for a person of ordinary skill in the art to experiment to reach another workable product or process. In the design and fabrication of microfluidic chips and devices, the selection of optimal experimental conditions including structural geometry and dimensions affects fluidic transport parameters such as pressure and flow rate which in turn affect transport profile of the desired analytes in the samples. Thus, the “a thickness of about 0.5 µm to about 2 µm” are a result effective variables.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified a method of Kaurand Jindal to include that the inner surface material of the plurality of interconnected channels of the SEC microfluidic device has a thickness of about 0.5 µm to about 2 µm, as taught by Spaid for the benefit of providing a resultant signal via the interaction of the sample analytes with the reagent (Spaid, Para 0023), allowing for the provision of a way to quickly run multiple different analyses on low volume samples. It would be desirable to have a way to quickly and inexpensively screen large numbers of samples with multiple analyses to develop more reliable marker thresholds, and marker pattern correlations so that more asymptomatic cancers can be confidently identified (Spaid, Para 0006).
Regarding Claim 45, the method of claim 1 is obvious over Kaur in view of Jindal.
The combination of Kaur and Jindal does not teach each of the plurality of interconnected channels of the SEC microfluidic device has a length of about 2 cm to about 50 cm, a width of about 1 µm to about 15 µm, and/or a depth of about 1 µm to about 15 µm.
In the analogous art of systems and methods of running multiple different analyses on a microfluidic device, Spaid teaches that each of the plurality of interconnected channels (See Para 0045…reaction channels can include reagents in the form of selective media) of the SEC microfluidic device (referred to as microfluidic device [Fig. 1, ref. 103]) has a length (See Para 0100… Proportioning and flow rates of solutions are controlled for each assay, e.g., by channel design and independent control of forces driving flows in each assay channel. The flow rate through each channel is affected by the resistance offered, e.g., by channel length, cross section, and geometry.), a width (See Para 0100… Proportioning and flow rates of solutions are controlled for each assay, e.g., by channel design and independent control of forces driving flows in each assay channel. The flow rate through each channel is affected by the resistance offered, e.g., by channel length, cross section, and geometry.) and/or a depth of about 1 µm to about 15 µm (this limitation “and/or…” is interpreted as optional).
Regarding the “a length of about 2 cm to about 50 cm, a width of about 1 µm to about 15 µm”, MPEP § 2144.05, Part II, Subpart B holds that a particular parameter that is recognized as a result effective variable (“a variable that achieves a recognized result”) would be one, but not the only motivation for a person of ordinary skill in the art to experiment to reach another workable product or process. In the design and fabrication of microfluidic chips and devices, the selection of optimal experimental conditions including structural geometry and dimensions affects fluidic transport parameters such as pressure and flow rate which in turn affect transport profile of the desired analytes in the samples. Thus, the “a length of about 2 cm to about 50 cm, a width of about 1 µm to about 15 µm” are a result effective variables.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified a method of Kaurand Jindal to include that each of the plurality of interconnected channels of the SEC microfluidic device has a length of about 2 cm to about 50 cm, a width of about 1 µm to about 15 µm, and/or a depth of about 1 µm to about 15 µm (Spaid, Para 0023), allowing for the provision of a way to quickly run multiple different analyses on low volume samples. It would be desirable to have a way to quickly and inexpensively screen large numbers of samples with multiple analyses to develop more reliable marker thresholds, and marker pattern correlations so that more asymptomatic cancers can be confidently identified (Spaid, Para 0006).
Regarding Claim 48, the method of claim 1 is obvious over Kaur in view of Jindal.
The combination of Kaur and Jindal does not teach that the plurality of interconnected channels of the SEC microfluidic device are formed via a pillar array.
In the analogous art of systems and methods of running multiple different analyses on a microfluidic device, Spaid teaches that the plurality of interconnected channels (See Para 0080… The capillary pathway may include a first channel 48 in fluid communication with a second channel 50.) of the SEC microfluidic device (See Para 0080… The microfluidic separation system 3) are formed via a pillar array (See Para 0080… A number of microstructures in the form of pillars 46 are provided between the channels 48, 50; See Para 0029…The microstructures may be in the form of grooved surfaces, pillars, or any form that defines size exclusion spacings.).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified a method of Kaur and Jindal to include that the plurality of interconnected channels of the SEC microfluidic device are formed via a pillar array, as taught by Spaid for the benefit of providing a resultant signal via the interaction of the sample analytes with the reagent (Spaid, Para 0023), allowing for the provision of a way to quickly run multiple different analyses on low volume samples. It would be desirable to have a way to quickly and inexpensively screen large numbers of samples with multiple analyses to develop more reliable marker thresholds, and marker pattern correlations so that more asymptomatic cancers can be confidently identified (Spaid, Para 0006).
Regarding Claim 264, the method of claim 1 is obvious over Kaur in view of Jindal.
The combination of Kaur and Jindal does not teach that the plurality of interconnected channels of the SEC microfluidic device are configured in an open tubular format.
In the analogous art of systems and methods of running multiple different analyses on a microfluidic device, Spaid teaches that the plurality of interconnected channels (See Para 0045…reaction channels can include reagents in the form of selective media) of the SEC microfluidic device (referred to as microfluidic device [Fig. 1, ref. 103]) are configured in an open tubular format (See Fig. 1, ref. 107 for the open tubular format).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified a method of Kaur and Jindal to include that the plurality of interconnected channels of the SEC microfluidic device are configured in an open tubular format, as taught by Spaid for the benefit of providing signals resulting from contact with samples (Spaid, Para 0007), allowing for the provision of a way to quickly run multiple different analyses on low volume samples. It would be desirable to have a way to quickly and inexpensively screen large numbers of samples with multiple analyses to develop more reliable marker thresholds, and marker pattern correlations so that more asymptomatic cancers can be confidently identified (Spaid, Para 0006).
Regarding Claim 265, the method of claim 1 is obvious over Kaur in view of Jindal.
The combination of Kaur and Jindal does not teach that the plurality of interconnected channels of the SEC microfluidic device comprises 8 or more interconnected channels.
In the analogous art of systems and methods of running multiple different analyses on a microfluidic device, Spaid teaches that the plurality of interconnected channels (See Para 0045…reaction channels can include reagents in the form of selective media) of the SEC microfluidic device (referred to as microfluidic device [Fig. 1, ref. 103]) comprises 8 or more interconnected channels (See Para 0076… Microfluidic devices can be designed to run single or multiple samples or reagents in single or multiple reaction channels; See Para 0080… In an aspect of the invention, …8 or more different assays. In methods of the invention, a single microfluidic device can run two or more different assays, 8 or more different assays, 25 or more different assays, 100 or more different assays, or 250 or more different assays, e.g., by receiving different reagents into reaction channels of the device.).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified a method of Kaur and Jindal to include that the plurality of interconnected channels of the SEC microfluidic device are configured in an open tubular format, as taught by Spaid for the benefit of providing multiple assay results by running multiple samples and/or multiple reagents on the same microfluidic device. (Spaid, Para 0080), allowing for the provision of a way to quickly run multiple different analyses on low volume samples. It would be desirable to have a way to quickly and inexpensively screen large numbers of samples with multiple analyses to develop more reliable marker thresholds, and marker pattern correlations so that more asymptomatic cancers can be confidently identified (Spaid, Para 0006).
Regarding Claim 266, the method of claim 1 is obvious over Kaur in view of Jindal.
The combination of Kaur and Jindal does not teach that each of the plurality of interconnected channels of the SEC microfluidic device is in fluidic communication with an input port of the SEC microfluidic device via an upstream network of connection channels.
In the analogous art of systems and methods of running multiple different analyses on a microfluidic device, Spaid teaches that each of the plurality of interconnected channels (See Para 0045…reaction channels) of the SEC microfluidic device (referred to as microfluidic device [Fig. 1, ref. 103; Para 0034]) is in fluidic communication with an input port (See Annotated Fig. 3.) of the SEC microfluidic device (referred to as microfluidic device [Fig. 1, ref. 103; Para 0034]) via an upstream network of connection channels (See Annotated Fig. 3.)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified a method of Kaur and Jindal to include that each of the plurality of interconnected channels of the SEC microfluidic device is in fluidic communication with an input port of the SEC microfluidic device via an upstream network of connection channels, as taught by Spaid for the benefit of providing multiple assay results by running multiple samples and/or multiple reagents on the same microfluidic device. (Spaid, Para 0080), allowing for the provision of a way to quickly run multiple different analyses on low volume samples. It would be desirable to have a way to quickly and inexpensively screen large numbers of samples with multiple analyses to develop more reliable marker thresholds, and marker pattern correlations so that more asymptomatic cancers can be confidently identified (Spaid, Para 0006).
Regarding Claim 267, the method of claim 1 is obvious over Kaur in view of Jindal.
The combination of Kaur and Jindal does not teach that each of the plurality of interconnected channels of the SEC microfluidic device is in fluidic communication with an output port of the SEC microfluidic device via a downstream network of connection channels.
In the analogous art of systems and methods of running multiple different analyses on a microfluidic device, Spaid teaches that each of the plurality of interconnected channels (See Para 0045…reaction channels) of the SEC microfluidic device (referred to as microfluidic device [Fig. 1, ref. 103; Para 0034]) is in fluidic communication with an output port (See Annotated Fig. 3.) of the SEC microfluidic device (referred to as microfluidic device [Fig. 1, ref. 103; Para 0034]) via a downstream network of connection channels (See Annotated Fig. 3.)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified a method of Kaur and Jindal to include that each of the plurality of interconnected channels of the SEC microfluidic device is in fluidic communication with an output port of the SEC microfluidic device via an downstream network of connection channels, as taught by Spaid for the benefit of providing multiple assay results by running multiple samples and/or multiple reagents on the same microfluidic device. (Spaid, Para 0080), allowing for the provision of a way to quickly run multiple different analyses on low volume samples. It would be desirable to have a way to quickly and inexpensively screen large numbers of samples with multiple analyses to develop more reliable marker thresholds, and marker pattern correlations so that more asymptomatic cancers can be confidently identified (Spaid, Para 0006).
Claim 52 is rejected under 35 U.S.C. 103 as being unpatentable over Kaur et al. (US20170315132A1) in view of Jindal et al. (US20020150926A1) as applied to claim 1 above, and further in view of Krkljus (US20160197344A1).
Regarding Claim 52, the method of claim 1 is obvious over Kaur in view of Jindal.
The combination of Kaur and Jindal does not teach that the SEC microfluidic device comprises a quartz substrate.
In the analogous art of a process for the preparation of lithium iron phosphate-type electrode materials, Krkljus teaches that the SEC microfluidic device (See Para 0032… Size exclusion chromatography is preferred) comprises a quartz substrate (See Para 0032… As stationary phase fused silica columns can be used).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified a method of Kaur and Jindal to include that the SEC microfluidic device comprises a quartz substrate, as taught by Krkljus for the benefit of having the molecular weights of organic polymers to be measured by size-exclusion chromatography or light scattering (Krkljus, Para 0032), allowing for the provision of a process for preparing an electrode material with less decrease in energy storage capacity at high current density in comparison to materials from prior art. Furthermore, it is object of the present invention to make a material available which can be used to produce electrodes in lithium-ion batteries with high performance (Krkljus, Para 0006).
Claim 69 is rejected under 35 U.S.C. 103 as being unpatentable over Kaur et al. (US20170315132A1) in view of Jindal et al. (US20020150926A1) as applied to claim 1 above, and further in view of Brohman (US20190041391A1).
Regarding Claim 69, the method of claim 67 is obvious over Kaur in view of Jindal.
Kaur teaches that the enzyme-based digestion technique (See Para 0008…which may include optional washing and eluting steps to further purify or enrich the ADC, or ADC fragments, to be analyzed.; See Para 0009…these analysis methods may also include dephosphorylating the ADC, reducing and/or denaturing the ADC, and enzymatically digesting the ADC. Enzymatic digestion of the ADC may be accomplished by contacting the antibody with a proteolytic enzyme, for example, trypsin, chymotrypsin, papain, pepsin, LysN, LysC, AspN, GluC, ArgC, PNGaseF, or combinations of such enzymes, thereby teaching “proteolytic technique” hereby teaching “an enzyme-based digestion technique”).
The combination of Kaur and Jindal does not teach a step of diluting the fraction eluted from the SEC microfluidic device, and wherein the diluting comprises admixing the fraction eluted from the SEC microfluidic device with water to reach a concentration of the chaotropic agent.
In the analogous art of proteomic biomarkers of spontaneous preterm birth, proteomic biomarkers of term birth, and methods of use thereof. In particular, the present disclosure provides tools for determining whether a pregnant subject is at an increased risk for premature delivery, as well as tools for decreasing a pregnant subject's risk for premature delivery, Brohman teaches a step of diluting the fraction eluted from the SEC microfluidic device, and wherein the diluting comprises admixing the fraction eluted from the SEC microfluidic device with water to reach a concentration of the chaotropic agent (See Para 0008… In some embodiments, the size-exclusion chromatography comprises elution with water; See Para 0011… In some embodiments, the preparing step further comprises denaturation using urea, reduction using dithiothreitol, alkylation using iodoacetamine, and digestion using trypsin prior to the size exclusion chromatography).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified a method of Kaur and Jindal to include that a step of diluting the fraction eluted from the SEC microfluidic device, and wherein the diluting comprises admixing the fraction eluted from the SEC microfluidic device with water to reach a concentration of the chaotropic agent, as taught by Brohman for the benefit of preparing the microparticle-enriched fraction using size-exclusion chromatography (Brohman, Para 0008), allowing for the provision of noninvasive tools for determining whether a pregnant subject is at an increased risk for premature delivery, as well as tools for decreasing a pregnant subject's risk for premature delivery (Brohman, Para 0005).
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
ThermoFisher ( POROS™ R2 Prepacked Reversed-Phase Columns )
(https://www.thermofisher.com/order/catalog/product/1111212) teaches that POROS R2 is a 2000 angstrom pore size Poly[styrenevinylbenzene] particle, suitable for the reversed-phase separation of biomolecules. 10 micron particle size is used for the highest resolution chromatography, and is suitable for analytical to small scale preparative separation of biomolecules. 20 micron particle size is used for high resolution and small scale preparative to semi-preparative separation of biomolecules.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to OYELEYE ALEXANDER ALABI whose telephone number is (571)272-1678. The examiner can normally be reached on M-F 7:30am-5:30pm.
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, Lyle Alexander can be reached on (571) 272-1254. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see https://ppair-my.uspto.gov/pair/PrivatePair. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/OYELEYE ALEXANDER ALABI/ Examiner, Art Unit 1797
Prosecution Insights