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 .
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 1, 13, 17, 19, and 25 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.
The term “about” in claims 1, 13, 17, 19, and 25 is a relative term which renders the claim indefinite. The term “about” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It’s not clear what the meets and bounds for the term about is in the claim as written. Is it +/- 5 degrees? Is it +/- 25 degrees? Is it +/- 5 degrees/second? Is it +/- 25 degrees/second? Is it +/- 2 minutes? Is it +/- 10 minutes? It’s not clear.
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.
Claim(s) 1, 6-10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Schenttini et al. (U.S. Patent Application Publication Number 2015/0301058; hereinafter referred to as Schenttini), further in view of Lauber et al. (U.S. Patent Application Publication Number 2022/0034852; hereinafter referred to as Lauber), further in view of Bardotti et al. (U.S. Patent Application Publication Number 2010/0219335;hereinafter referred to as Bardotti), and further in view of Atwood et al. (U.S. Patent Application Publication Number 2002/0072112; hereinafter referred to as Atwood).
With respect to claim 1, Schenttini discloses a method for performing a liquid chromatography-mass spectrometry analysis of a proteolytic glycopeptide derived from a biological sample comprising a glycoprotein (see at least paragraphs [0021] and [0561]), the method comprising: subjecting the biological sample to a thermal denaturation technique to produce a denatured sample (see at least paragraph [0992]) followed by a proteolytic digestion technique to produce a proteolytically digested sample comprising the proteolytic glycopeptide (see at least paragraphs [0213], [0992], and [0994]), wherein the thermal denaturation technique subjects the biological sample to a thermal cycle comprising a thermal treatment of about 60 °C to about 100°C with a hold time of at least about 1 minute (see at least paragraphs [0992], and [0994]), and wherein the proteolytic digestion technique comprises adding an amount of one or more proteolytic enzymes and incubating for a digestion incubation time (see at least paragraph [0213]), introducing the proteolytically digested sample to a liquid chromatography (LC) system of a LC- MS system (see at least paragraph [0538]); and performing a LC-MS technique to introduce the proteolytic glycopeptide to a mass spectrometer (MS) system (see at least paragraph [0561]). Schenttini fails to disclose wherein a lid temperature during the thermal cycle is at least about 2 °C higher than the temperature of a block temperature during the thermal cycle, wherein the proteolytic digestion technique comprises quenching the one or more proteolytic enzymes following the digestion incubation time; wherein the LC-MS technique comprises a period of diversion of an initial eluate comprising a salt, and wherein the LC system comprises a reversed-phase chromatography column. However, Lauber teaches proteolytic digestion technique comprises quenching the one or more proteolytic enzymes following the digestion incubation time (see at least paragraph [0443] of Lauber. Therefore, it would have been obvious to one skilled in the art at the time the invention was filed to modify the method of Schenttini by quenching proteolytic enzymes and reversed-phase chromatography as taught by Lauber in order to stop a digestion reaction by quenching the proteolytic enzyme reaction to prevent over-digestion and performing reverse-phase chromatography to isolate glycopeptides that can be subjected to mass spectrometric analysis. Further, while Schenttini doesn’t disclose certain features, Bardotti teaches the LC-MS technique comprises a period of diversion of an initial eluate comprising a salt, and wherein the LC system comprises a reversed-phase chromatography column (see at least paragraph [0011] of Bardotti). Therefore, it would have been obvious to one skilled in the art at the time the invention was filed to modify the method of Schenttini by diverting an initial eluate as taught by Bardotti. to maximize the collection and purification of glycopeptides for mass spectrometric analysis. Finally, while Schenttini fails to disclose the specifics regarding the lid and block temperatures, Atwood discloses a thermal cycler wherein the central processing unit 20 includes appropriate electronics to sense the temperature of the heated cover 14 and control electric resistance heaters therein to maintain the cover 14 at a predetermined temperature (see at least paragraph [0099] of Atwood). Therefore, it would have been obvious to one skilled in the art at the time the invention was filed to use the thermal cycler parameters disclosed in Atwood with the system of Schenttini in order to ensure there is no condensation of the samples during a thermal cycle as condensation can foul results or ruin samples.
With respect to claim 6, the method of claim 1, wherein the proteolytic glycopeptide comprises a hydrophilic glycan portion is disclosed in at least paragraph [0042] of Schenttini.
With respect to claim 7, the method of claim 1, wherein the proteolytic glycopeptide comprises a hydrophobic glycan portion is disclosed in at least paragraph [0782] of Schenttini.
With respect to claim 8, the method of claim 1, wherein the biological sample is derived from a human is disclosed in at least paragraph [0160] of Schenttini.
With respect to claim 9, the method of claim 1, wherein the biological sample is a blood sample or a derivative thereof is disclosed in at least paragraph [0162] of Schenttini.
With respect to claim 10, the method of claim 1, wherein the biological sample is a plasma sample is disclosed in at least paragraph [0162] of Schenttini.
With respect to claim 11, the method of claim 1, wherein the biological sample is a serum sample is disclosed in at least paragraph [0162] of Schenttini.
With respect to claim 12, the method of claim 1, wherein the biological sample is not subjected to a high-abundant protein depletion technique prior to the thermal denaturation technique is disclosed in at least paragraph [0130] of Schenttini.
With respect to claim 13, the method of claim 1, wherein the thermal cycle comprises a block set temperature of about 15 °C to about 100 °C with a hold time of at least about 1 minute is taught in at least paragraphs [0017] and [0202] of Atwood.
With respect to claim 16, the method of claim 1, wherein the thermal cycle is performed in a thermal cycler comprising a lid temperature control element is taught in at least paragraph [0099] of Atwood.
With respect to claim 17, the method of claim 1, wherein the thermal cycle comprises a ramp rate between the block set temperature and the block ending temperature of about 1 °C/second to about 10 °C/second is taught in at least paragraphs [1170] and [1171] of Atwood.
With respect to claim 19, the method of claim 1, wherein the digestion incubation time is at least about 20 minutes is disclosed in at least paragraph [1226] of Schenttini.
With respect to claim 23, the method of claim 1, wherein each of the one or more proteolytic enzymes is selected from the group consisting of trypsin and LysC is disclosed in at least paragraph [0220] of Schenttini.
With respect to claim 24, the method of claim 23, wherein the trypsin is methylated and/or acetylated is disclosed in at least paragraph [0163] of Schenttini.
With respect to claim 25, the method of claim 1, wherein the amount of the one or more proteolytic enzymes is in a proteolytic enzyme concentration to sample protein weight ratio of about 1:20 to about 1:40 is disclosed in at least paragraphs [0160] and [1614] of Schenttini.
With respect to claim 26, the method of claim 1, wherein quenching the one or more proteolytic enzymes is performed using an acid is taught in at least paragraph [0121] of Lauber.
With respect to claim 27, the method of claim 26, wherein the acid is formic acid (FA) or trifluoroacetic acid (TFA), or a mixture thereof is taught in at least paragraph [0121] of Lauber.
Claim(s) 2-4 is/are rejected under 35 U.S.C. 103 as being unpatentable over Schenttini in view of Lauber, further in view of Bardotti, further in view of Atwood as applied to claim 1 above, and further in view of Wu (U.S. Patent Application Publication Number 2020/0355582).
With respect to claim 2, Schenttini in view of Lauber, further in view of Bardotti, further in view of Atwood fails to teach or disclose the method of claim 1, further comprising subjecting the denatured sample to a reduction technique followed by an alkylation technique prior to the proteolytic digestion technique. However, Wu teaches a denatured sample to a reduction technique followed by an alkylation technique prior to the proteolytic digestion technique (see at least paragraphs [0004] and [0007] of Wu). Therefore, it would have been obvious to one skilled in the art at the time the invention was filed to modify the method of Schenttini in view of Lauber, further in view of Bardotti by reducing and alkylating a denatured sample as taught by Wu in order to prepare peptides for mass spectrometry to more accurately determine the composition of the peptides in a sample.
With respect to claim 3, Schenttini in view of Lauber, further in view of Bardotti, further in view of Atwood fails to teach or disclose the method of claim 2, wherein the reduction technique comprises subjecting the denatured sample to the reduction technique to produce a reduced sample, wherein the reduction technique comprises adding an amount of a reducing agent to the denatured sample and incubating for a reducing incubation time. However, Wu teaches a reduction technique comprises subjecting the denatured sample to the reduction technique to produce a reduced sample, wherein the reduction technique comprises adding an amount of a reducing agent to the denatured sample and incubating for a reducing incubation time (see at least paragraphs [0004] and [0007] of Wu). Therefore, it would have been obvious to one skilled in the art at the time the invention was filed to modify the method of Schenttini in view of Lauber, further in view of Bardotti by reducing and alkylating a denatured sample as taught by Wu in order to prepare peptides for mass spectrometry to more accurately determine the composition of the peptides in a sample.
With respect to claim 4, Schenttini in view of Lauber, further in view of Bardotti, further in view of Atwood fails to teach or disclose the method of claim 2, wherein the alkylation technique comprises subjecting the reduced sample to the alkylation technique to produce an alkylated sample, wherein the alkylation technique comprises adding an amount of an alkylating agent to the reduced sample and incubating substantially in in a low light condition for an alkylation incubation time, and wherein the alkylated technique comprises quenching the alkylating agent following the alkylation incubation time. However, Wu teaches an alkylation technique comprises subjecting the reduced sample to the alkylation technique to produce an alkylated sample, wherein the alkylation technique comprises adding an amount of an alkylating agent to the reduced sample and incubating for an alkylation incubation time, and wherein the alkylated technique comprises quenching the alkylating agent following the alkylation incubation time (see at least paragraph [0007] of Wu). Therefore, it would have been obvious to one skilled in the art at the time the invention was filed to modify the method of Schenttini in view of Lauber, further in view of Bardotti by reducing and alkylating a denatured sample as taught by Wu in order to prepare peptides for mass spectrometry to more accurately determine the composition of the peptides in a sample.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RODNEY T FRANK whose telephone number is (571)272-2193. The examiner can normally be reached M-F 9am-5:30pm.
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/RODNEY T FRANK/Examiner, Art Unit 2855
August 8, 2026
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