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 .
Claim Status
Claims 19 and 22-40 are pending and examined. Claims 1-18 and 20-21 are canceled.
Information Disclosure Statement
The information disclosure statement (IDS) received on 2/26/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
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 19 and 22-40 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 19, the preamble recites, “A method for performing mass spectrometry…”. However, none of the recited method steps in claim 19 include the actual performing of mass spectrometry. Step e) in claim 19 recites, “assaying the biological sample”. However, if a different kind of assaying, e.g. protein sequencing, an immunoassay, etc. is performed, then where is the mass spectrometry actually performed, as recited in the preamble? Further clarification is needed.
Claims 22-40 are rejected at least for depending on a rejected claim.
Regarding claim 36, the claim recites, “the assaying is selected from the group consisting of mass spectrometry, protein sequencing, binding each protein in the proteins to a pair of antibodies, binding a protein in the proteins to an aptamer, and an immunoassay”. However, as the preamble is drawn to a method for performing mass spectrometry, it is unclear how any of the recited assays other than mass spectrometry will result in a method for performing mass spectrometry. Further clarification is needed.
Claims 37-39 are rejected at least for depending on a rejected claim.
Claim 38 recites the limitation "the molecule" in Ln. 3. There is insufficient antecedent basis for this limitation in the claim.
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 19, 22-28, 30-31, 34-37, and 40 are rejected under 35 U.S.C. 103 as being unpatentable over Zhao et al. (WO Pub. No. 2020/198209; hereinafter Zhao; already of record on the IDS received 2/26/2025) in view of Wilcox et al. (US Pub. No. 2023/0089033; hereinafter Wilcox) and Monopoli et al. (US Pub. No. 2025/0035619; hereinafter Monopoli).
Regarding claim 19, Zhao discloses a method for performing mass spectrometry ([0217]-[0220]). The method comprises:
(a) providing a biological sample comprising one or more peptides and a solvent, wherein the one or more peptides comprise proteolytically cleaved derivatives of proteins ([0217]-[0220], proteins are bound particles, and digested using trypsin).
(b) determining an amount of the one or more peptides in the biological sample ([0217]-[0220], peptide concentration was measuring by a quantitative colorimetric peptide assay kit).
(c) drying the biological sample to remove at least a portion of the solvent ([0217]-[0220], the peptide eluates were lyophilized).
(d) reconstituting the biological sample with a second solvent ([0217]-[0220], the peptide eluates were lyophilized and reconstituted).
(e) assaying the biological sample ([0217]-[0220], the peptide eluates were analyzed by nano LC/MS/MS).
Zhao fails to explicitly disclose that the peptides are on a surface; and
That the reconstituting is based at least in part on the amount of the one or more peptides, such that the biological sample comprises a predetermined concentration of the one or more peptides.
Wilcox is in the analogous field of mass spectrometry (Wilcox [0003]). Wilxoc teaches peptides on a surface (Wilcox; [0003], [0037]). It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the method of Zhao with the teachings of Wilcox so that the peptides are on a surface as in Wilcox, as Wilcox teaches that adsorbing peptides onto a surface of a particle can be used to improve the measurement of low abundance biomolecules when high abundance biomolecules would normally interfere with accurate measurements of the low abundance biomolecules (Wilcox [0022]).
Modified Zhao fails to explicitly disclose that the reconstituting is based at least in part on the amount of the one or more peptides, such that the biological sample comprises a predetermined concentration of the one or more peptides.
Monopoli is in the analogous field of mass spectrometry (Monopoli; [0007]-[0016], [0052]-[0053]). Monopoli teaches reconstituting based at least in part on an amount of one or more peptides, such that a biological sample comprises a predetermined concentration of the one or more peptides (Monopoli; [0023]-[0024], [0028], [0032]). It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the method of modified Zhao with the teachings of Monopoli so that the reconstituting is based at least in part on the amount of the one or more peptides, such that the biological sample comprises a predetermined concentration of the one or more peptides, in order to lead to an excess of surface area to the total proteins (Monopoli; [0023]-[0024], [0028], [0032]), thereby ensuring that the proteins are bound to the particles.
Regarding claim 22, modified Zhao discloses the method of claim 19.
Modified Zhao fails to explicitly disclose that the one or more peptides comprise a plurality of peptides, and the assaying comprises determining a relative amount between at least two peptides in the plurality of peptides.
Wilcox further teaches a plurality of peptides, where assaying comprises determining a relative amount between at least two peptides in the plurality of peptides (Wilcox [0037]). It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the method of modified Zhao with the further teachings of Wilcox so that the one or more peptides comprise a plurality of peptides, and the assaying comprises determining a relative amount between at least two peptides in the plurality of peptides, in order to perform proteomic analysis on a biological sample (Wilcox; [0024], [0037], [0103]-[0104]).
Regarding claim 23, modified Zhao discloses the method of claim 19.
Modified Zhao fails to explicitly disclose that the surface comprises a particle surface.
Wilcox further discloses that the surface comprises a particle surface, the particle being a nanoparticle surface (Wilcox; [0037], [0060]). The proteins form a corona on the particle surface (Wilcox [0052]). It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the method of modified Zhao with the further teachings of Wilcox so that the surface comprises a particle surface, the surface being a nanoparticle surface, as Wilcox teaches that a nanoparticle surface can be used to adsorb low abundant proteins in order to enable accurate and precise quantification of these low abundant proteins (Wilcox [0086]). Further, it would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the method of modified Zhao with the further teachings of Wilcox so that the proteins form a corona on the particle surface, as Wilcox teaches that adsorbed proteins that make up a biomolecule corona can be used to generate proteomic data (Wilcox [0109]).
Regarding claim 24, modified Zhao discloses the method of claim 23. Modified Zhao further discloses that the particle surface is a nanoparticle surface or a microparticle surface (see Claim 23 above at Wilcox teaching a nanoparticle surface in [0037], [0060]).
Regarding claim 25, modified Zhao discloses the method of claim 23.
Modified Zhao fails to explicitly disclose that the particle surface comprises pores.
Monopoli further teaches a particle surface comprising pores (Monopoli; [0032], [0036]). It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the method of modified Zhao with the further teachings of Monopoli so that the particle surface comprises pores, as Monopoli teaches that porous particles have increased surface area, which can be used to ensure that there is an excess of surface area on the particles relative to the proteins (Monopoli; [0024], [0032], [0036]), thereby ensuring that the proteins are bound to the particles.
Regarding claim 26, modified Zhao discloses the method of claim 19.
Modified Zhao fails to explicitly disclose that wherein the proteins are bound on the surface via adsorption.
Wilcox further teaches that the proteins are bound on the surface via adsorption (Wilcox [0037]). It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the method of modified Zhao with the further teachings of Wilcox so that the proteins are bound on the surface via adsorption, in order to quantify peptides that have adsorbed on the surface (Wilcox [0037]).
Regarding claim 27, modified Zhao discloses the method of claim 23. Modified Zhao further discloses that the proteins form a corona on the particle surface (see Claim 23 above at Wilcox teaching the proteins forming a corona on the particle surface in [0052]).
Regarding claim 28, modified Zhao discloses the method of claim 19.
Modified Zhao fails to explicitly disclose that the proteins are bound on the surface via non-specific binding.
Monopoli further teaches proteins that are bound on a surface via non-specific binding (Monopoli [0032], the particles bind non-specifically to proteins). It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the method of modified Zhao with the further teachings of Monopoli so that the proteins are bound on the surface via non-specific binding, as Monopoli teaches that non-specific binding can be used to enrich specific proteins to perform proteomic analysis (Monopoli; [0032], [0112]).
Regarding claim 30, modified Zhao discloses the method of claim 19.
Modified Zhao fails to explicitly disclose that the predetermined concentration is based at least in part on one or more physicochemical properties of the surface.
Monopoli further teaches that the predetermined concentration is based at least in part on one or more physicochemical properties of the surface, the one or more physicochemical properties comprising sample to surface ratio (Monopoli; [0023]-[0024], [0028], [0032]). It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the method of modified Zhao with the further teachings of Monopoli so that the predetermined concentration is based at least in part on one or more physicochemical properties of the surface, the one or more physicochemical properties comprising sample to surface ratio, as Monopoli teaches that ensuring that the surface area of the particles being in excess to the amount of protein in the sample will ensure that proteins are bound to the particles (Monopoli; [0023]-[0024], [0028], [0032]). Further, for analysis of certain proteins, controlling the surface area of the particle relative to the protein concentration is necessary in order to elucidate a disease-indicating glycoprotein and/or glycan profile that would otherwise be hidden in standard samples (Monopoli [0017]).
Regarding claim 31, modified Zhao discloses the method of claim 30. Modified Zhao further discloses that the one or more physicochemical properties comprise: sample to surface ratio, incubation time, pH, salt concentration, ionic strength, solvent composition, solvent dielectric constant, crowding agent concentration, temperature, sample composition, surfactant concentration, concentration of enzymes, activity of enzymes, chemical reactions, concentrations of small molecules, surface chemistry, or any combination thereof (see Claim 30 above at Monopoli teaching sample to surface ratio in [0023]-[0024], [0028], [0032]).
Regarding claim 34, modified Zhao discloses the method of claim 19. Modified Zhao further discloses, prior to (a), proteolytically cleaving the proteins to generate the one or more peptides (Zhao [0217]-[0220]).
Regarding claim 35, modified Zhao discloses the method of claim 34.
Modified Zhao fails to explicitly disclose, prior to proteolytically cleaving, contacting the proteins with the surface.
However, Zhao teaches, prior to proteolytically cleaving, contacting the proteins with a surface (Zhao [0217]-[0220]). It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the method of modified Zhao to comprise, prior to proteolytically cleaving, contacting the proteins with the surface, in order to be able to remove unbound protein prior to processing, thereby removing residual background unbound protein that may be present in a sample (Zhao; [0181], [0217]-[0220]).
Regarding claim 36, modified Zhao discloses the method of claim 19. Modified Zhao further discloses that the assaying is selected from the group consisting of mass spectrometry, protein sequencing, binding each protein in the proteins to a pair of antibodies, binding a protein in the proteins to an aptamer, and an immunoassay (Zhao [0217]-[0220]).
Regarding claim 37, modified Zhao discloses the method of claim 36. Modified Zhao further discloses that the mass spectrometry comprises liquid-chromatography tandem mass spectrometry (LC-MS/MS) (Zhao [0217]-[0220]).
Regarding claim 40, modified Zhao discloses the method of claim 19. Modified Zhao further discloses performing (a)-(e) for a second plurality of peptides in serial or in parallel (Zhao; [0004], serial interrogation, [0130], processing biofluids in parallel).
Claims 29 and 38-39 are rejected under 35 U.S.C. 103 as being unpatentable over Zhao in view of Wilcox and Monopoli as applied to claims 19, 22-28, 30-31, 34-37, and 40 above, and further in view of Huang (US Pub. No. 2016/0041178).
Regarding claim 29, modified Zhao discloses the method of claim 19. Modified Zhao fails to explicitly disclose that the proteins are bound on the surface via specific binding.
Huang is in the analogous field of performing biological assays (Huang; [0005], [0038]). Huang teaches binding a target analyte on a surface via specific binding (Huang [0009]). It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the method of modified Zhao with the teachings of Huang so that the proteins are bound on the surface via specific binding, in order to be able to perform an assay involving a specific target analyte (Huang [0009]).
Regarding claim 38, modified Zhao discloses the method of claim 36.
Modified Zhao fails to explicitly disclose that the pair of antibodies comprises complementary single-stranded nucleic acid sequences attached thereto, such that when the pair of antibodies bind to the molecule, the complementary nucleic acids hybridize to form a double stranded nucleic acid.
Huang teaches a pair of antibodies that comprise complementary single-stranded nucleic acid sequences attached thereto, such that when the pair of antibodies bind to a molecule, the complementary nucleic acids hybridize to form a double stranded nucleic acid (Huang; [0006], see also Claim 18). The double stranded nucleic acid is configured to form a binding complex with a polymerase and a plurality of nucleotides, nucleosides, nucleotide analogs and/or nucleoside analogs to perform an amplification reaction to produce a detectable signal (Huang; [0006], see also Claim 18). It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the method of modified Zhao with the teachings of Huang so that the pair of antibodies comprises complementary single-stranded nucleic acid sequences attached thereto, such that when the pair of antibodies bind to the molecule, the complementary nucleic acids hybridize to form a double stranded nucleic acid, and the double stranded nucleic acid is configured to form a binding complex with a polymerase and a plurality of nucleotides, nucleosides, nucleotide analogs and/or nucleoside analogs to perform an amplification reaction to produce a detectable signal, in order to determine whether a target analyte is present in a sample (Huang; [0006], see also Claim 18).
Regarding claim 39, modified Zhao discloses the method of claim 38. Modified Zhao further discloses that the double stranded nucleic acid is configured to form a binding complex with a polymerase and a plurality of nucleotides, nucleosides, nucleotide analogs, and/or nucleoside analogs to perform an amplification reaction to produce a detectable signal (see Claim 38 above at Huang teaching the claimed double stranded nucleic acid in [0006], see Claim 18).
Claims 32-33 are rejected under 35 U.S.C. 103 as being unpatentable over Zhao in view of Wilcox and Monopoli as applied to claims 19, 22-28, 30-31, 34-37, and 40 above, and further in view of Kimzey et al. (US Pub. No. 2018/0156809; hereinafter Kimzey).
Regarding claim 32, modified Zhao discloses the method of claim 19.
Modified Zhao fails to explicitly disclose that the determining comprises contacting the biological sample with a reagent configured to output a signal, wherein a strength of the signal is correlated with the amount of the one or more peptides in the biological sample.
Kimzey is in the analogous field of detection, identification, and quantification of peptides and proteins (Kimzey [0007]). Kimzey teaches contacting a sample with a reagent configured to output a signal, where a strength of the signal is correlated with the amount of one or more peptides in the sample (Kimzey; [0007], [0010]). The reagent is a fluorescing reagent and the signal comprises a fluorescent signal (Kimzey; [0007], [0010]). It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the method of modified Zhao with the teachings of Kimzey so that the determining comprises contacting the biological sample with a reagent configured to output a signal, wherein a strength of the signal is correlated with the amount of the one or more peptides in the biological sample, the reagent comprises a fluorescing reagent and the signal comprises a fluorescent signal, as Kimzey teaches that measuring the fluorescence intensity of peptides/proteins can be used to quantify the peptides/proteins (Kimzey; [0007], [0010]).
Regarding claim 33, modified Zhao discloses the method of claim 32. Modified Zhao further discloses that the reagent comprises a fluorescing reagent and the signal comprises a fluorescent signal (see Claim 32 above at Kimzey teaching a fluorescing reagent and fluorescent signal in [0007], [0010]).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to John McGuirk whose telephone number is (571)272-1949. The examiner can normally be reached M-F 8am-530pm.
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/JOHN MCGUIRK/Primary Examiner, Art Unit 1798
