DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or
under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. This application claims benefit of
the foreign application CHINA 201911140968.3 filed 11/20/2019. Based on the filing receipt, the effective filing date of this application is November 20, 2019 which is the filing date of foreign application CHINA 201911140968.3 from which the benefit of priority is claimed.
Status of Claims
Claims 3, 10, and 16 are cancelled by the applicant.
Claims 1, 2, 4-9, 11-15, and 17-20 are pending and examined herein.
Withdrawn Rejections
The rejection of claims 1-17 on the grounds of 35 U.S.C. 112(b) has been withdrawn, necessitated by amendment filed 2025-08-20.
The rejection of claims 1-5 and 8-17 on the grounds of 35 U.S.C. 102(a)(1) has been withdrawn, necessitated by amendment filed 2025-08-20.
The rejection of claim 6 on the grounds of 35 U.S.C. 103 has been withdrawn, necessitated by amendment filed 2025-08-20.
New rejections, necessitated by amendment filed 2025-08-20, are discussed below.
Claim Objections
Claims 1, 2, and 4 are objected to because of the following informalities:
Claim 1 recites "the first control sample contains the first protein and no the ligand" when it should recite "the first control sample contains the first protein .
Claim when it should recite "the Nth protein without the ligand".
Claim 4 recites “wherein the separating the first mixture and separating the second mixture are both by centrifugation” when it should recite “wherein separating the first mixture and separating the second mixture are both by centrifugation”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 12 is newly 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, “a volumetric percentage of the solvent in each ligand sample or each control sample is 9-22%, wherein a concentration of ascorbic acid is 1-15 mM, or a concentration of citric acid is 1-5 mM”. The claim is indefinite because under typical lab conditions, ascorbic acid cannot exist at 1-15 mM while at a volumetric percentage of 9-22%. Similarly, citric acid cannot exist at 1-5 mM while at a volumetric percentage of 9-22%. 9% ascorbic acid, assuming the standard density of an aqueous solution and a molar mass of 176.12 g/mol from pubchem (https://pubchem.ncbi.nlm.nih.gov/compound/Ascorbic-acid), will have a concentration of about 511 mM. 9% citric acid, assuming the standard density of an aqueous solution and a molar mass of 192.12 g/mol from pubchem (https://pubchem.ncbi.nlm.nih.gov/compound/citric-acid), will have a concentration of about 468 mM. For these reasons the metes and bounds of claim 12 cannot be ascertained.
For the purposes of compact prosecution, claim 12 will be interpreted to mean “a volumetric percentage of the solvent in each ligand sample or each control sample is 9-22%, or the solvent is a concentration of ascorbic acid of 1-15 mM, or the solvent is a concentration of citric acid of 1-5 mM”. The solvent is either ascorbic acid at 1-15 mM or 9-22% or citric acid at 1-5 mM or 9-22%.
Claim Rejections - 35 USC § 103
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.
Claims 1, 2, 4, 5, 7-9, 11, 13-15, 18, and 19 are newly rejected under 35 U.S.C. 103 as being unpatentable over Meng, et al. (“Chemical Denaturation and Protein Precipitation Approach for
Discovery and Quantitation of Protein−Drug Interactions”, published 2018-07-11, cited in PTO-892 dated 2025-06-12) in view of Wang, et al. (“A new chromatographic approach to analyze methylproteome with enhanced lysine methylation identification performance”, published 2019-03-20) as evidenced by the compound summary of guanidine hydrochloride from PubChem (https://pubchem.ncbi.nlm.nih.gov/compound/Guanidine-
Hydrochloride, cited in PTO-892 dated 2025-06-12).
Meng teaches a method for detecting the interaction between a ligand and a protein based on solvent-induced protein precipitation, comprising: A) mixing a solvent a ligand sample containing a protein and a ligand to denature and precipitate the protein then separating the mixture to obtain the precipitated protein and the supernatant; B) mixing an equal amount of the solvent with a control sample to denature and precipitate the protein then separating the mixture to obtain the precipitated protein and the supernatant, wherein the control sample contains the protein without the ligand; C) measuring the protein concentration in the precipitated protein or the supernatant of step A) ; D) measuring the protein concentration in the precipitated protein or the supernatant of step B); E) comparing the measurement from step C) to the measurement of step D), as in claim 1 (see, e.g., solvent-induced protein
precipitation - p. 9250, col. 2, under “CPP Analysis.”; with and without a ligand - p. 9250, col. 2,
under “CPP Analysis.”; equal amount of solvent is added to the protein samples with and
without a ligand to denature and precipitate the proteins, the protein abundances in
supernatant and/or precipitate in the ligand group and control group are measured – p. 9252, col. 1, under “Figure 1.”; comparing the differences of protein abundances in the ligand group and the control group – p. 9251, col. 2 para. 3: “Protein hits were selected using the following
criteria: (i) the normalized protein intensities in the (−) and (+) ligand groups were significantly
different”). The application’s specification clarifies that “The solvent includes but not limited to
one or more of solvents, acidic agents, alkaline agents, metal ions or salts” (see, e.g., p. 4, lines
20-21). The denaturing agent, guanidine hydrochloride (GdmCl), of Meng is equivalent to a
solvent because it is a salt and a protein denaturant as evidenced by the compound summary of
GdmCl from PubChem (https://pubchem.ncbi.nlm.nih.gov/compound/Guanidine-
Hydrochloride).
Meng teaches the first ligand sample is a member of a ligand group comprising a N number of ligand samples each containing the ligand and one of a second protein to a Nth protein, respectively, wherein the first protein to the Nth protein are different from one another, and the first control sample is a member of a control group comprising the N number of control samples, each containing one of the second protein to the Nth protein without the ligand, the method further comprising: carrying out step a) to step e) for each of remaining members of the ligand group and the control group to obtain a second protein abundance to a Nth protein abundance and a second corresponding protein abundance to a Nth corresponding protein abundance; obtaining a second difference in abundance to a Nth difference in abundance corresponding to the second to the Nth protein, respectively; and identifying, amongst the first protein to the Nth protein, one or more target proteins when the difference in abundance thereof satisfy a predefined criterion, wherein N is an integer of 2 or more, as in claim 2 (see, e.g., protein solution incubated with ligand group and control
group - p. 9250, col. 2, under “CPP Analysis.”; add equal amount of denaturing solvent - p.
9250, col. 2, under “CPP Analysis.”; quantify the abundance of each protein in supernatant
and/or precipitate of the ligand and control group - p. 9249, under “ABSTRACT:”; compare the
abundance difference of each protein in the ligand group and the control group to determine
the target(s) of a ligand - p. 9251, col. 2 para. 3: “Protein hits were selected using the following
criteria: (i) the normalized protein intensities in the (−) and (+) ligand groups were significantly
different”).
Meng teaches separating the mixtures are by centrifugation, as in claim 4 (see, e.g., p. 9252, col. 1, under “Figure 1.”).
Meng teaches each ligand sample or each control sample contains a plurality of proteins derived from a human, as in claim 5 (see, e.g., p. 9249, under “ABSTRACT”: “The technique was
also used to identify protein targets of sinefungin, a broad-based methyltransferase inhibitor, in a human MCF-7 cell lysate”). It is understood that the human cell lysates used in the approach contain a plurality of proteins.
Meng teaches the ligand sample proteins are in natural conformation, as in claim 7 (see, e.g., p. 9250, under “Cell Culture and Lysis”, col. 2, para. 2: “Cell lysis was accomplished using zirconia/silica beads (1 mm) at 4 °C with 20 s of disruption 20 times with 1 min intervals on ice in between. The cell lysate was centrifuged at 14 000g and 4 °C for 10 min, and the supernatant was saved for subsequent analysis”).
Meng teaches the ligand is a drug, as in claim 8 (see, e.g., p. 9249, under “ABSTRACT:”).
Meng teaches each of the ligand samples has a concentration of ligand that is the same as one another, as in claim 9 (see, e.g., p. 9250, under “CPP Analysis.”: “The final concentration of drug was 100 μM in the CsA-binding experiment”).
Meng teaches that step A) is carried out by mixing the solvent and the ligand sample at 20-30° for 20 minutes and that step B) is carried out by mixing the solvent and the control sample at 20-30° for 20 minutes, as in claim 13 (see, e.g., p. 9250, under “CPP Analysis.”: “In all experiments, the (+) and (−) ligand containing lysate samples were distributed into a series of
GdmCl-containing buffers (PBS pH 7.4) with the final GdmCl concentrations ranging from 0 to 2.5 M. The final volume in each buffer was 20 μL. The final concentration of drug was 100
μM in the CsA-binding experiment, 20 μM in the geldanamycin binding experiment, and 0.2, 1.2, or 2.5 mM in the sinefungin binding experiments. The solutions were equilibrated at room temperature for 10 min before 480 μL of deionized water was added into each solution to initiate protein precipitation. After 10 min, the samples were centrifuged”). It is understood that the GdmCl-containing buffer, the solvent in Meng, is incubated with the lysate samples with and without the ligand for a total time of 20 minutes at room temperature (between 20-30°), which is equivalent to steps A) and B).
Meng teaches the protein is measured by label quantification, wherein the label quantification is TMT, as in claim 14 (see, e.g., p. 9250, under “CPP Analysis.”: “The TMT-10plex labeling scheme involved labeling the protein samples derived from each of the denaturant concentrations in the (−) ligand samples with the reagents from one TMT-10plex and labeling each of the denaturant concentrations in the (+) ligand samples with the reagents from another TMT-10plex”).
Meng teaches quantifying the protein abundance in the ligand group and the control group after solvent treatment utilizing mass spectrometry with Data Dependent Acquisition, as in claim 15 (see, e.g., p. 9251, col. 1, para. 1).
Meng teaches identifying a protein as the target protein when the difference between the measurement with and without the ligand satisfies a predefined criterion, as in claim 18 (see, e.g., p. 9251, col. 2 para. 3: “Protein hits were selected using the following criteria: (i) the normalized protein intensities in the (−) and (+) ligand groups were significantly different (i.e., different by at least 1.645σ or 3σ, depending on the experiment)”).
Meng teaches the ligand sample contains a plurality of proteins that includes the target protein and the control sample contains the same plurality of protein that include the first protein, as in claim 19 (see, e.g., p. 9250, under “CPP Analysis.”: “In all experiments, the (+) and (−) ligand containing lysate samples were distributed into a series of GdmCl-containing buffers (PBS pH 7.4) with the final GdmCl concentrations ranging from 0 to 2.5 M”). Again, it is understood that cell lysates contain a plurality of proteins.
Meng fails to teach the solvent is acetone, ethanol, acetic acid, or a combination thereof, as in claim 1. Meng fails to teach the solvent is has a volumetric ratio of acetone: ethanol: acetic acid = 50: 50: 0.1, as in claim 11.
However, in a journal article on proteome analysis, Wang rectifies these deficiencies. Wang discloses, “5 mL of solvent (acetone: ethanol: acetic acid = 50:50:0.1) was added for precipitation” to cell lysates, as in claims 1 and 11 (see, e.g., p. 112, under “2.2. Cell lysis and protein digestion”).
It would have been prima facie obvious to the person of ordinary skill in the art to make
and use the claimed invention from the disclosures of Meng and Wang. Such would have
been considered a simple substitution of equivalent elements as Meng teaches the use of the solvent GdmCl in deionized water for denaturing and precipitating proteins and Wang teaches the solvent acetone: ethanol: acetic acid at a volumetric ratio of 50:50:0.1 for denaturing and precipitating protein. As is stated in MPEP §2144.06, substituting one equivalent element for another known for the same purpose renders an invention obvious and an “express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982)." The person of ordinary skill in the art would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references.
Claims 1, 2, 4, 5, 7-9, 12-15, 18, and 19 are newly rejected under 35 U.S.C. 103 as being unpatentable over Meng, et al. (cited above) in view of Zhao, et al. (“Simultaneous determination of six isoflavonoids in rat plasma after administration of total flavonoid from Gegen by ultra-HPLC-MS/MS”, published 2012-05-15) as evidenced by the compound summary of GdmCl from PubChem (https://pubchem.ncbi.nlm.nih.gov/compound/Guanidine-
Hydrochloride).
Meng teaches a method for detecting the interaction between a ligand and a protein based on solvent-induced protein precipitation, comprising: A) mixing a solvent a ligand sample containing a protein and a ligand to denature and precipitate the protein then separating the mixture to obtain the precipitated protein and the supernatant; B) mixing an equal amount of the solvent with a control sample to denature and precipitate the protein then separating the mixture to obtain the precipitated protein and the supernatant, wherein the control sample contains the protein without the ligand; C) measuring the protein concentration in the precipitated protein or the supernatant of step A) ; D) measuring the protein concentration in the precipitated protein or the supernatant of step B); E) comparing the measurement from step C) to the measurement of step D), as in claim 1 (see, e.g., solvent-induced protein
precipitation - p. 9250, col. 2, under “CPP Analysis.”; with and without a ligand - p. 9250, col. 2,
under “CPP Analysis.”; equal amount of solvent is added to the protein samples with and
without a ligand to denature and precipitate the proteins, the protein abundances in
supernatant and/or precipitate in the ligand group and control group are measured – p. 9252, col. 1, under “Figure 1.”; comparing the differences of protein abundances in the ligand group and the control group – p. 9251, col. 2 para. 3: “Protein hits were selected using the following
criteria: (i) the normalized protein intensities in the (−) and (+) ligand groups were significantly
different”). The application’s specification clarifies that “The solvent includes but not limited to
one or more of solvents, acidic agents, alkaline agents, metal ions or salts” (see, e.g., p. 4, lines
20-21). The denaturing agent, guanidine hydrochloride (GdmCl), of Meng is equivalent to a
solvent because it is a salt and a protein denaturant as evidenced by the compound summary of
GdmCl from PubChem (https://pubchem.ncbi.nlm.nih.gov/compound/Guanidine-
Hydrochloride).
Meng teaches the first ligand sample is a member of a ligand group comprising a N number of ligand samples each containing the ligand and one of a second protein to a Nth protein, respectively, wherein the first protein to the Nth protein are different from one another, and the first control sample is a member of a control group comprising the N number of control samples, each containing one of the second protein to the Nth protein without the ligand, the method further comprising: carrying out step a) to step e) for each of remaining members of the ligand group and the control group to obtain a second protein abundance to a Nth protein abundance and a second corresponding protein abundance to a Nth corresponding protein abundance; obtaining a second difference in abundance to a Nth difference in abundance corresponding to the second to the Nth protein, respectively; and identifying, amongst the first protein to the Nth protein, one or more target proteins when the difference in abundance thereof satisfy a predefined criterion, wherein N is an integer of 2 or more, as in claim 2 (see, e.g., protein solution incubated with ligand group and control
group - p. 9250, col. 2, under “CPP Analysis.”; add equal amount of denaturing solvent - p.
9250, col. 2, under “CPP Analysis.”; quantify the abundance of each protein in supernatant
and/or precipitate of the ligand and control group - p. 9249, under “ABSTRACT:”; compare the
abundance difference of each protein in the ligand group and the control group to determine
the target(s) of a ligand - p. 9251, col. 2 para. 3: “Protein hits were selected using the following
criteria: (i) the normalized protein intensities in the (−) and (+) ligand groups were significantly
different”).
Meng teaches separating the mixtures are by centrifugation, as in claim 4 (see, e.g., p. 9252, col. 1, under “Figure 1.”).
Meng teaches each ligand sample or each control sample contains a plurality of proteins derived from a human, as in claim 5 (see, e.g., p. 9249, under “ABSTRACT”: “The technique was
also used to identify protein targets of sinefungin, a broad-based methyltransferase inhibitor, in a human MCF-7 cell lysate”). It is understood that the human cell lysates used in the approach contain a plurality of proteins.
Meng teaches the ligand sample proteins are in natural conformation, as in claim 7 (see, e.g., p. 9250, under “Cell Culture and Lysis”, col. 2, para. 2: “Cell lysis was accomplished using zirconia/silica beads (1 mm) at 4 °C with 20 s of disruption 20 times with 1 min intervals on ice in between. The cell lysate was centrifuged at 14 000g and 4 °C for 10 min, and the supernatant was saved for subsequent analysis”).
Meng teaches the ligand is a drug, as in claim 8 (see, e.g., p. 9249, under “ABSTRACT:”).
Meng teaches each of the ligand samples has a concentration of ligand that is the same as one another, as in claim 9 (see, e.g., p. 9250, under “CPP Analysis.”: “The final concentration of drug was 100 μM in the CsA-binding experiment”).
Meng teaches that step A) is carried out by mixing the solvent and the ligand sample at 20-30° for 20 minutes and that step B) is carried out by mixing the solvent and the control sample at 20-30° for 20 minutes, as in claim 10 (see, e.g., p. 9250, under “CPP Analysis.”: “In all experiments, the (+) and (−) ligand containing lysate samples were distributed into a series of
GdmCl-containing buffers (PBS pH 7.4) with the final GdmCl concentrations ranging from 0 to 2.5 M. The final volume in each buffer was 20 μL. The final concentration of drug was 100
μM in the CsA-binding experiment, 20 μM in the geldanamycin binding experiment, and 0.2, 1.2, or 2.5 mM in the sinefungin binding experiments. The solutions were equilibrated at room temperature for 10 min before 480 μL of deionized water was added into each solution to initiate protein precipitation. After 10 min, the samples were centrifuged”). It is understood that the GdmCl-containing buffer, the solvent in Meng, is incubated with the lysate samples with and without the ligand for a total time of 20 minutes at room temperature (between 20-30°), which is equivalent to steps A) and B).
Meng teaches the protein is measured by label quantification, wherein the label quantification is TMT, as in claim 14 (see, e.g., p. 9250, under “CPP Analysis.”: “The TMT-10plex labeling scheme involved labeling the protein samples derived from each of the denaturant concentrations in the (−) ligand samples with the reagents from one TMT-10plex and labeling each of the denaturant concentrations in the (+) ligand samples with the reagents from another TMT-10plex”).
Meng teaches quantifying the protein abundance in the ligand group and the control group after solvent treatment utilizing mass spectrometry with Data Dependent Acquisition, as in claim 15 (see, e.g., p. 9251, col. 1, para. 1).
Meng teaches identifying a protein as the target protein when the difference between the measurement with and without the ligand satisfies a predefined criterion, as in claim 18 (see, e.g., p. 9251, col. 2 para. 3: “Protein hits were selected using the following criteria: (i) the normalized protein intensities in the (−) and (+) ligand groups were significantly different (i.e., different by at least 1.645σ or 3σ, depending on the experiment)”).
Meng teaches the ligand sample contains a plurality of proteins that includes the target protein and the control sample contains the same plurality of protein that include the first protein, as in claim 19 (see, e.g., p. 9250, under “CPP Analysis.”: “In all experiments, the (+) and (−) ligand containing lysate samples were distributed into a series of GdmCl-containing buffers (PBS pH 7.4) with the final GdmCl concentrations ranging from 0 to 2.5 M”). Again, it is understood that cell lysates contain a plurality of proteins.
Meng fails to teach the solvent is ascorbic acid, as in claim 1. Meng fails to teach the solvent has a volumetric percentage of 10%, as in claim 12.
However, in a journal article on a HPLC-MS/MS method, Zhao rectifies these deficiencies. Zhao discloses, “After the addition of methanol containing 0.1% formic acid and 10% ascorbic acid, the analytes and rutoside were obtained by protein precipitation”, as in claims 1 and 11 (see p. 984, under abstract).
It would have been prima facie obvious to the person of ordinary skill in the art to make
and use the claimed invention from the disclosures of Meng and Zhao. Such would have
been considered a simple substitution of equivalent elements as Meng teaches the use of the solvent GdmCl in deionized water for denaturing and precipitating proteins and Zhao teaches the solvent is 10% ascorbic acid for denaturing and precipitating protein. As is stated in MPEP §2144.06, substituting one equivalent element for another known for the same purpose renders an invention obvious and an “express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982)." The person of ordinary skill in the art would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references.
Claim 6 is newly rejected under 35 U.S.C. 103 as being unpatentable over Meng (cited above) and Wang (cited above), as applied to claims 1, 2, 4, 5, 7-9, 11, 13-15, 18, and 19, and further in view of Trainor (“The importance of plasma protein binding in drug discovery”, published 2007-01-16, cited in PTO-892 dated 2025-06-12).
Meng and Wang teaches as set forth above, but fail to teach the protein solution includes blood or plasma, as in claim 6. However, Trainor rectifies this deficiency in a journal article on the role of plasma protein binding in drug discovery. Trainor recites, “Plasma protein binding of drugs is a well-recognised phenomena, but it is only recently that the implications for drug action in vivo have been fully appreciated” (see, e.g., p. 51, under abstract).
Meng, Wang, and Trainor are analogous to the field of the claimed invention because they are both in the field of protein-drug binding. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to incorporate the teachings of Trainor into the methods of Meng and Wang by measuring the affinity of proteins and ligands, specifically drugs, in blood or plasma samples. An artisan would have been motivated to do so because “[p]lasma proteins, by virtue of their high concentration, control the free drug concentration in plasma and in compartments in equilibrium with plasma, thereby, effectively attenuating drug potency in vivo” (see, e.g., Trainor, p. 51, under abstract). An artisan would have had a reasonable expectation of success based on the given disclosures.
Claim 6 is newly rejected under 35 U.S.C. 103 as being unpatentable over Meng (cited above) and Zhao (cited above), as applied to claims 1, 2, 4, 5, 7-9, 11, 13-15, 18, and 19, and further in view of Trainor (cited above).
Meng and Zhao teaches as set forth above, but fails to teach the protein solution includes blood or plasma, as in claim 6. However, Trainor rectifies this deficiency in a journal article on the role of plasma protein binding in drug discovery. Trainor recites, “Plasma protein binding of drugs is a well-recognised phenomena, but it is only recently that the implications for drug action in vivo have been fully appreciated” (see, e.g., p. 51, under abstract).
Meng, Zhao, and Trainor are analogous to the field of the claimed invention because they are both in the field of protein-drug binding. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to incorporate the teachings of Trainor into the methods of Meng and Zhao by measuring the affinity of proteins and ligands, specifically drugs, in blood or plasma samples. An artisan would have been motivated to do so because “[p]lasma proteins, by virtue of their high concentration, control the free drug concentration in plasma and in compartments in equilibrium with plasma, thereby, effectively attenuating drug potency in vivo” (see, e.g., Trainor, p. 51, under abstract). An artisan would have had a reasonable expectation of success based on the given disclosures.
Claims 17 and 20 are newly rejected under 35 U.S.C. 103 as being unpatentable over Meng (cited above) and Wang (cited above), as applied to claims 1, 2, 4, 5, 7-9, 11, 13-15, 18, and 19, and further in view Lomenick, et al. (“Target identification using drug affinity responsive target stability (DARTS)”, published 2009-12-22).
Meng and Wang teach as set forth above, especially that target proteins are identified by a predetermined criterion (see, e.g., p. 9251, col. 2 para. 3: “Protein hits were selected using the following criteria: (i) the normalized protein intensities in the (−) and (+) ligand groups were significantly different (i.e., different by at least 1.645σ or 3σ, depending on the experiment)”). But, the references fail to teach the predefined criterion is determined according to a fold change of protein abundance ≥ 2, as in claims 17 and 20.
However, in a journal article on target identification using drug affinity responsive target stability, Lomenick rectifies this deficiency. Lomenick teaches the predefined criterion is determined according to a fold change of protein abundance ≥ 2, as in claims 17 and 20 (see, e.g., p. 21985, under “Fig. 2.”, under panel “B”, under figure caption).
Meng, Wang, and Lomenick are analogous to the field of the claimed invention because they are all in the field of biological assays. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to incorporate the predefined criterion of Lomenick into the method of Meng and Wang. An artisan would have been motivated to do so because Lomenick disclosed that a known drug target, EF-1α, is identified by their predetermined criterion (see, e.g., p. 21985, col. 1, para. 1-2). An artisan would have a reasonable expectation of success based on the given disclosures.
Claims 17 and 20 are newly rejected under 35 U.S.C. 103 as being unpatentable over Meng (cited above) and Zhao (cited above), as applied to claims 1, 2, 4, 5, 7-9, 11, 13-15, 18, and 19, and further in view Lomenick, et al. (“Target identification using drug affinity responsive target stability (DARTS)”, published 2009-12-22).
Meng and Zhao teach as set forth above, especially that target proteins are identified by a predetermined criterion (see, e.g., p. 9251, col. 2 para. 3: “Protein hits were selected using the following criteria: (i) the normalized protein intensities in the (−) and (+) ligand groups were significantly different (i.e., different by at least 1.645σ or 3σ, depending on the experiment)”). But, the references fail to teach the predefined criterion is determined according to a fold change of protein abundance ≥ 2, as in claims 17 and 20.
However, in a journal article on target identification using drug affinity responsive target stability, Lomenick rectifies this deficiency. Lomenick teaches the predefined criterion is determined according to a fold change of protein abundance ≥ 2, as in claims 17 and 20 (see, e.g., p. 21985, under “Fig. 2.”, under panel “B”, under figure caption).
Meng, Zhao, and Lomenick are analogous to the field of the claimed invention because they are all in the field of biological assays. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to incorporate the predefined criterion of Lomenick into the method of Meng and Zhao. An artisan would have been motivated to do so because Lomenick disclosed that a known drug target, EF-1α, is identified by their predetermined criterion (see, e.g., p. 21985, col. 1, para. 1-2). An artisan would have a reasonable expectation of success based on the given disclosures.
Response to Arguments
Rejections under 35 U.S.C. 112
The applicant’s amendments, including the cancellation of claims 3 and 16, cured the deficiencies and rendered the 35 U.S.C. 112 rejections moot. For these reasons, 35 U.S.C. 112 rejections have been withdrawn, as stated above.
Rejections under 35 U.S.C. 102
The applicant argues that Meng (cited above) does not teach “the solvent is selected from acetone, methanol, ethanol, acetic acid, ascorbic acid, citric acid, trifluoroacetic acid, and mixtures thereof” as in amended claim 1. The office agrees with this argument, therefore, the 35 U.S.C. 102 rejection is withdrawn.
The applicant continues by arguing that the solvent of Meng is not a solvent that denatures and precipitates proteins. While the office does not agree with the applicant’s assertion, the argument is irrelevant to the 35 U.S.C. 102 rejection because the claim recites, “mixing an amount of a solvent and a first ligand sample containing a first protein and a ligand to denature and precipitate”. The broadest reasonable interpretation of the claim includes solvents added “to induce denature and precipitate” with the addition water. The purpose of the solvent of Meng is to denature then precipitate, therefore, the solvent meets the broadest reasonable interpretation of a solvent mixed “to denature and precipitate” as in amended claim 1.
The applicant argues, without evidence, that the recited solvents in amended claim 1 are not obvious variants of the GdmCl-containing buffer solution in Meng. However, the solvent of Meng is mixed with proteins and ligands to denature and precipitate, therefore, solvents that have the same function would be seen as functional equivalents.
Rejections under 35 U.S.C. 103
The applicant submits that Trainor (cited above) does not cure the deficiencies of Meng regarding the amended claim 1. The office agrees with the statement, therefore, the 35 U.S.C. 103 rejection of claim 6 over Meng in view of Trainor has been withdrawn. New rejections have been added, as stated above, necessitated by amendment.
Conclusion
No claims are allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
The compound summary of GdmCl from PubChem (https://pubchem.ncbi.nlm.nih.gov/compound/Guanidine-Hydrochloride) discloses guanidine hydrochloride (GdmCl) is equivalent to a solvent because it is a salt and a protein denaturant.
The compound summary of ascorbic acid by Pubchem (https://pubchem.ncbi.nlm.nih.gov/compound/Ascorbic-acid) discloses the molar mass of ascorbic acid.
The compound summary of citric acid from Pubchem (https://pubchem.ncbi.nlm.nih.gov/compound/citric-acid) discloses the molar mass of citric acid.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHAEL C SVEIVEN whose telephone number is (703)756-4653. The examiner can normally be reached Monday to Friday - 8AM to 5PM PST.
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/MICHAEL CAMERON SVEIVEN/Examiner, Art Unit 1678
/Ann Montgomery/Primary Examiner, Art Unit 1678
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