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 .
Election/Restrictions
Applicant’s election without traverse of Claims 1-13 in the reply filed on 3/13/2026 is acknowledged.
Claims 14-18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected medical product, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 3/13/2026.
Claims 1-13 are pending examination in this response.
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 3, 4, 7, 8, 9 and 10 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 3, the phrases "such a" (interpreted as “such as”) and “preferably” render the claim indefinite because it is unclear whether the limitations following the phrases are part of the claimed invention. See MPEP § 2173.05(d).
Claim 4 recites “wherein the trapping column has the same packing material as the peptide mapping column”. There is lack of antecedent basis for this limitation in the claim since claim 4 depends on claim 1, and claim 1 does not previously recite peptide mapping column. For the purpose of examination, claim 4 will be interpreted as depending on claim 3.
Regarding claim 7, the phrases "such as" and “preferably” render the claim indefinite because it is unclear whether the limitations following the phrases are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 8, the phrase “preferably” in the limitation “preferably the two digestion columns are connected in parallel” is indefinite because it is unclear whether the limitation following the phrase is required by the claimed invention. See MPEP § 2173.05(d).
Regarding claim 9, the phrase “preferably” in the limitation “preferably wherein the two digestion columns are a Trypsin immobilized enzyme reactor and a LysC immobilized enzyme reactor” is indefinite because it is unclear whether the limitation following the phrase is required by the claimed invention. See MPEP § 2173.05(d).
Regarding claim 10, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
The limitation will be interpreted as “comprising a reduction module having a reduction column, wherein the reduction module and the digestion module are fluidly connected when the digestion module and the trapping module are fluidly connected
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.
Claims 1, 2, 8, 9, 11, and 13 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Jindal et al. (US 6794148 B2).
Regarding claim 1, Jindal teaches “A multidimensional liquid chromatograph (LC) system” (Col. 6 lines 38-40 and FIG. 3, is a schematic representations of a splitter interface (sampler) between a liquid chromatography column and a mass spectrometer in the apparatus of the invention); “for characterizing a sample of therapeutic antibodies” (Col. 5 lines 42-45, The sample solutions may be obtained by the digestion of any protein, including post-translationally modified proteins, antibodies, etc.); “comprising a digestion module having a digestion column containing an immobilized proteolytic enzyme,” (Fig. 3 and col 37 lines 60-65, col 28 lines 60-67, col. 30 lines 42-47, affinity column 114, The IgG activated POROS.TM. was packed into 4.6 mm D.times.100 mm L PEEK columns using Self Pack.RTM. assembly on BioCAD.TM. at 20 ml/min flow rate. 5 to 50 mgs peptide library (natural peptide library or polyclonal antibody digest) dissolved in 0.5 to 2.5 ml of 10 mM PBS (pH 7.5) was injected onto the column at flow rate of 0.5 ml/min. In different embodiments, first column 114 is an affinity column for partitioning a library based upon a first physico-chemical property, and second column 118 is another affinity column to partition the first exit stream 116 based upon a second physico-chemical property. Third column 132 may be a reversed phase column capable of accumulating the desired ligand thereon prior to eluting the desired ligand into third exit stream 134. As a first step, whether the mAb immobilized onto the XL cartridge retained its ability to bind the peptide YGGFL (SEQ ID NO: 1) was investigated. The peptide solution (20 nmol) was injected onto the affinity column and then unbound peptide was removed by washing the column with PBS, pH, 7.4.): “a trapping module having a trapping column for holding the sample after digestion in the digestion module” ( Fig. 3 col. 29 lines 3-5, Col. 28 lines 35-38, and Col. 19 lines 58-65, Second column 118 is an affinity column capable of partitioning based upon a second physicochemical property. First exit stream 116 is optionally directed to a second column 118 to partition candidate ligands based on a second, different physics chemical property, to generate a second exit stream 120. The second column may be a size exclusion column. The eluted target/ligand complexes from the first 60 column are then introduced to the second column, along with a known ligand. The known ligand can be any ligand known to bind at the particular epitope one is seeking a binder to. Thus, the known ligand will compete with the ligand on the target/ligand complex, and displace ligands 65 which bind at the selected site on the target molecule.); “a separation module having a separation column for separating analytes in the sample after release of the sample from the trapping column,” (Fig. 3 and col. 28 lines 52-59 and col. 28 lines 64-67, Second exit stream 120 is optionally introduced into a second multi-valved splitter 130 which directs the second exit stream 120, into a third column 132. A sample of the third exit stream 134 containing a selected ligand may optionally be inserted into a third sample splitter 140, and then into a mass spectrometer 136 for determination of the charge to mass ratio of the ligand. A display 138 may be connected thereto. Third column 132 may be a reversed phase column capable of accumulating the desired ligand thereon prior to eluting the desired ligand into third exit stream 134.); “a first valve assembly” (Fig. 3, Col. 28 lines 42-58, Optionally, first multi valved splitter 124 may be positioned between the first column 114 and second column 118 to direct the first exit stream 116 to the interface 122, to the detector 125, where, if ligand is present, exit stream 116 is reintroduced to valve 124, or if no ligand is present, exit stream 116 is directed to waste stream 126.); “and a second valve assembly” (Fig.3, and col. 28 lines 52-54, Second exit stream 120 is optionally introduced into a second multi-valved splitter 130 which directs the second exit stream 120, into a third column 132.); “wherein the first valve assembly and the second valve assembly are configured such that the digestion column and the trapping column are fluidly connectable; the trapping column and the separation column are fluidly connectable; and the separation module and the digestion module are not fluidly connectable.” (Fig. 3, corresponding number 124 connects 114 and 118 and 130 connects 118 and 132 and neither valve connects 114 to 132).
Regarding claim 2, Jindal teaches all of claim 1 as above in addition to “wherein the first valve assembly comprises a plurality of ports configured so that some combinations of the plurality of ports can be fluidly connected in a first position of the first valve assembly and other combinations of the plurality of ports can be fluidly connected in a second position of the first valve assembly; and “(Fig. 3, multi valved splitter 124, with ports shown by multiple arrows going into and out of valve 124.); “the second valve assembly comprises a plurality of ports configured so that some combinations of the plurality of ports can be fluidly connected in a first position of the second valve assembly and other combinations of the plurality of ports can be fluidly connected in a second position of the second valve assembly” (Fig. 3, second multi-valved splitter 130, with ports shown by multiple arrows going into and out of valve 130.; “such that the digestion column and the trapping column are fluidly connected when the first valve assembly is in the second position and the second valve assembly is in a first position;” (Fig. 3, arrows from 116 to 124 and arrow pointing down to 118); “the trapping column and the separation column are fluidly connected when the second valve assembly is in a second position;” (Fig. 3, arrow from 120 to valve 130 and the arrow down to 132 column); “and the separation module and the digestion module are not fluidly connected in any combination of positions of the valve assemblies.” (Fig. 3, numbers 132 and 114).
Regarding claim 8, Jindal teaches all of claim 1 as above in addition to “(Col. 15 lines 25-37 and Col. 31 lines 40-49, The methods of the invention use a tandem column chromatographic technique: any column capable of separating molecules can be used in the methods of the invention. Thus, depending on the result sought, the columns in the system may be chosen from the group consisting of affinity columns, size exclusion columns, and/or reversed phase columns. As used herein, the term "tandem mode" indicates that at least two columns are involved in the system, either simultaneously, or sequentially. If the columns are run simultaneously in tandem mode, then sample solution may be split and delivered to each column. If they are run sequentially, the columns are arranged so that the eluate of one column is directly introduced into the second column. Control In order to confirm the specificity of the target immobilized affinity column for YGGFL (SEQ ID NO: 1), samples of the purchased peptide and the library (XXXFL) were analyzed in a parallel experiment using the control column prepared in Experiment 1. The chromatogram was identical except for the peak corresponding to YGGFL (SEQ ID NO: 1). In a parallel experiment. a peptide with the sequence YEYFL (SEQ ID NO: 2) (a known non-binder to the mAb was not retained by the affinity column.).
Regarding claim 9, Jindal teaches all of claim 8 as above in addition to “wherein the two digestion columns are connected in parallel such that in use the sample flow is split between the two columns” (Col. 15 lines 25-37, The methods of the invention use a tandem column chromatographic technique: any column capable of separating molecules can be used in the methods of the invention. Thus, depending on the result sought, the columns in the system may be chosen from the group consisting of affinity columns, size exclusion columns, and/or reversed phase columns. As used herein, the term "tandem mode" indicates that at least two columns are involved in the system, either simultaneously, or sequentially. If the columns are run simultaneously in tandem mode, then sample solution may be split and delivered to each column. If they are run sequentially, the columns are arranged so that the eluate of one column is directly introduced into the second column.).
Regarding claim 11, Jindal teaches all of claim 1 as above in addition to “further comprising a fractionation module having a fractionation column optionally wherein the fractionation column is selected from an ion exchange chromatography column, size exclusion chromatography column, a hydrophilic interaction chromatography column (HILIC), a hydrophobic interaction chromatography column (HIC) or a protein a affinity column.” (Col. 3 lines 51-64, Col. 32 lines 22-33, and Col. 26 lines 25-29, The library XXXFL was made on Fmoc-Leu WANG resin using standard procedures in an Advanced Chemtech librarian peptide synthesizer. Prior to screening the library (consisting of approximately 5800 pentamers) it was divided into an anionic and cationic fraction based on retention on the weak anion exchange column (material binding to the column when injected in 50 mM Iris, pH 6.7 was designated as the anionic fraction, while that passing through was the cationic fraction). Only the cationic fraction was screened using this paradigm. However, the cationic fraction represented> 2/3 of the total library based on peak area for the two fractions. Separating mixed species of ligand dissolved in a solvent into separate fractions of ligands, wherein each fraction is characterized by a different affinity or range of affinities for a preselected target molecule. Initially, the mixed ligand species are passed through a column comprising immobi- 55 lized target molecules so that the ligands will bind to the target. A series of column volumes of solvent then are passed through the column, and at least two subsets of the column volumes of solvent exiting the column are then passed through a ligand accumulator, thereby immobilizing ligands 60 characterized by separate ranges of affinity constants. The fractions containing ligands characterized by different ranges of affinities are then optionally eluted from the accumulator to separate them chemically for further screening or analysis. When the sampling valve is returned to position A, any residual sample left in the sample loop 32 is driven into the chromatography detector 26, fraction collector or waste, depending on the configuration of the system.
Regarding claim 13, Jindal teaches all of claim 1 as above in addition to “further comprising an analysis module for analyzing the sample after the sample has passed through the separation column.” (Fig. 3, mass spectrometer 136 from 132 (separation column).
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.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Jindal et al. (US 6794148 B2).
Regarding claim 6, Jindal teaches all of claim 1 as above but does not explicitly teach “” However, it would have been clearly within the ordinary skills of an artisan before the effective filing date of the claimed invention to have modified the invention of Jindal by having the digestion column be selected from a trypsin immobilized enzyme reactor, depending on particular goals of testing, since Jindal teaches enzymatic digestion using trypsin with different ratios in addition to a trypsin column within Col. 36 lines 38-44 and Col. 24 lines 40-50. It would have been a matter of an obvious engineering choice, to better adjust the apparatus to have this digestion within the digestion column in order to provide for a sample that is cleaner to travel within the separation column which is next.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Jindal et al. (US 6794148 B2) as applied to claim 1 and further in view of Wang (US 20190234960 A1).
Regarding claim 3, Jindal teaches all of claim 1 but does not explicitly teach “However Jindal does teach a HPLC column within Col. 34 lines 64-67.
Wang teaches a dual column LC-MS system and methods in addition to “within (Para [0033] and Fig. 1, a diagram of an exemplary system 100. System 100 contains column 101. Column 101 is typically an HPLC column packed with material for separating non-polar and/or hydrophobic peptides.)
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 Jindal to incorporate the teachings of Wang wherein the separation column is a HPLC column. Doing so increases the separation compacity of the device and allows for separation of more components within a mixture.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Jindal et al. (US 6794148 B2) and Wang (US 20190234960 A1) as applied to claim 3 above and in further view of Minohata et. al. (US 20200158701 A1).
Regarding claim 4, modified Jindal teaches all of claim 3 as above but does not teach “wherein the trapping column has the same packing material as the peptide mapping column.”.
Wang teaches an LC/MS/MS analysis: injecting a sample into a passage leading to a column group provided in a liquid chromatograph in addition to “wherein the trapping column has the same packing material as the peptide mapping column.”. (Paras [0035] and [0036], As for the plurality of kinds of packing materials, a plurality of packing materials which respectively correspond to different separation modes should be used. There are various separation modes in liquid chromatography, such as the reversed phase mode, normal phase mode, HILIC mode, ion exchange mode, ligand exchange mode, ion exclusion mode, size exclusion mode (GPC or GFC mode), and affinity mode. In the method for analyzing a sample according to the present invention, for example, a packing material corresponding to the ion exchange mode and one corresponding to the reversed phase mode can be used as the plurality of kinds of packing materials. It is also possible to use, as the plurality of kinds of packing materials, a plurality of packing materials which correspond to the same separation mode and differ from each other in the material (e.g. silica gel or polymer gel), shape, grain size or pore diameter of the base body forming the packing material, or in the kind of functional group bonded to the base body. The method for analyzing a sample according to the present invention can be realized, for example, by a liquid chromatograph mass spectrometer (LC-MS) as shown in FIG. 1. In the case of using a plurality of columns, all columns may be separation columns, or at least one column may be a trap 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 Jindal to incorporate the teachings of Wang wherein the trapping column has the same packing material as the peptide mapping column. Doing so allows both columns to interact with the same type of chemicals or analytes.
Regarding claim 5, modified Jindal teaches all of claim 1 as above but does not teach “valve assembly is in the first position and the second valve assembly in the first position.”. However Jindal does teach the liquid stream is driven through a column by a pump within Col. 25 lines 20-25.
Wang teaches “ (Para [0048], Port k of the second passage-switching valve 400 is connected to the solvent mixer 116 located in the passage extending from pump A to the second column 140.).
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 Jindal to incorporate the teachings of Wang wherein the trapping column has the same packing material as the peptide mapping column. Doing so allows for the trapping module to have independent control over the sample and the flow.
The recitation “when the first valve assembly is in the first position and the second valve assembly in the first position.” is capability of the orientation of the values however the connection of the second column (trapping column) to the pump is taught within para [0048] above.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Jindal et al. (US 6794148 B2) as applied to claim 1 above and in further view of Zhu et. al. (CN 110394105 A).
Regarding claim 7, Jindal teaches all of claim 1 as above but does not explicitly teach “
Zhu teaches a liquid phase chromatography in addition to “(Page 7, According to the present invention, there is provided a structure, through the rotating of the external magnetic steel drives the rotation of inner magnetic steel, thereby stirring and mixing into the liquid of the device inside the mixed into a uniform distribution of liquid conveyed to the chromatographic column for detection and analysis of the sample. the movement has stirring effect, comparing the static mixing naturally to be much better. at the same time, it can reduce the mixing volume furthest.).
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 Jindal to incorporate the teachings of Zhu ensures the buffers and reagents are homogenous which increases digestion which increases separation and identifications.
The recitation “such as static mixer or a zero delay volume T-Piece after the digestion column(s) in the direction of flow preferably wherein the first mixer is fluidly connected to the trapping pump when the first valve is in the second position” has been interpreted under broadest reasonable interpretation as an optional type of mixer and connections that are not required by the claimed invention.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Jindal et al. (US 6794148 B2) as applied to claim 1 above and in further view of Hughes (US 20060186028 A1).
Regarding claim 10, Jindal teaches all of claim 1 as above but does not explicitly teach “further comprising a reduction module having a reduction column wherein the reduction module and the digestion module are fluidly connected when the digestion module and the trapping module are fluidly connected such as when the first valve assembly is in the second position.”
Hughes teaches A mass spectrometer and a liquid chromatography system in addition to “further comprising a reduction module having a reduction column wherein the reduction module and the digestion module are fluidly connected when the digestion module and the trapping module are fluidly connected such as when the first valve assembly is in the second position.” (Paras [0044] [0086], and Fig. 1A, When the liquid chromatography system switches from the first mode of operation to the second mode of operation preferably the column head pressure associated with the first (analytical) column is preferably substantially reduced or removed in a time t.sub.2, wherein t.sub.2 is selected from the group consisting of: (i) .ltoreq.10 s; (ii) .ltoreq.9 s; (iii) .ltoreq.8 s; (iv) .ltoreq.7 s; (v) .ltoreq.6 s; (vi) .ltoreq.5 s; (vii) .ltoreq.4 s; (viii) .ltoreq.3 s; (ix) .ltoreq.2 s; (x) .ltoreq.1 s; (xi) .ltoreq.0.75 s; (xii) .ltoreq.0.5 s; (xiii) .ltoreq.0.25 s; (xiv) .ltoreq.0.1 s; and (xv) substantially instantaneously.) Therefore switching from first mode to second mode teaches of the first valve within claim 1 moving to provide that the modules are fluidly connected. In addition at that time the pressure is reduced and the number of ports or columns attached to the valves teach to a reduction module and the reduction column as they are capable of removing and reducing the pressure as taught within para [0044].
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 Jindal to incorporate the teachings of Hughes a reduction column fluid connected to the digestion column fluid connected to the trapping column. Doing so decreases analysis time as the device is more automated having the columns all together and fluidically connected.
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Jindal et al. (US 6794148 B2) as applied to claim 11 above and in further view of Lege (DE 102022106332 A1).
Regarding claim 12, Jindal teaches all of claim 11 as above but does not explicitly teach “further comprising a multiple heart cutting valve fluidly connected to the fractionation column and after the fractionation column in the direction of flow.”
Lege teaches liquid moving in a chromatographic column in addition to “further comprising a multiple heart cutting valve fluidly connected to the fractionation column and after the fractionation column in the direction of flow.” (Page 9 and 16, While exemplary embodiments of the invention may perform a restriction test in an injector, mixer, and/or fluid filter of the pump, other embodiments of the invention may be used for the entire flow path of an analyzer. Other examples are multiple heart cutting decks in 2D LC analyzers, 2D LC interface valves, fraction separator valves, etc. In a so-called heart cutting operating mode, the analysis device 10 can be used according to 5 a desired portion of the fluidic sample can be excised for analysis.).
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 Jindal to incorporate the teachings of Lege a reduction column fluid connected to the digestion column fluid connected to the trapping column. Doing so allows for isolation of a set sample fraction and allow precise fractions of the sample to flow to the next column.
Conclusion
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/V.E.H./Examiner, Art Unit 1798
/CHARLES CAPOZZI/Supervisory Patent Examiner, Art Unit 1798
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