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 Objections
Claim 19 is objected to because it recites “a mass detection signals” contains grammatical errors.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 8 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Claim 8 recites “said ion trap is maintained at a pressure in a range of about 1 mTorr to about 10 Torr.” However, the specification discloses resonant ion-trap fragmentation only at about 1 to about 10mTorr (See Spec. page 13, 3rd paragraph). The specification provides no guidance for operating the ion trap from above 10mTorr through 10 Torr. Because pressure affects ion confinement, collision damping, and resonant energy accumulation, consequently, operation over the undisclosed pressure range cannot reasonably be extrapolated from the disclosed 1-10mTorr embodiment without further technical guidance and thus practicing the claimed method throughout this undisclosed range would require undue experimentation for an ordinary skilled person in the art. Accordingly, the disclosure is not commensurate in scope with claim 8 and does not enable resonant ion-trap fragmentation throughout the claimed pressure range.
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 1-3, 5-7, 9-10, and 13-16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US 2013/0084645 A1 [hereinafter Coon].
Regarding Claim 1:
Coon teaches a method of performing mass spectrometry (Abstract), comprising:
selecting a precursor ion having an m/z ratio in an m/z range of interest from among a plurality of ions (paras. [0295-0297]: generates precursor ions with a nanoESI source, performs MS scan in a range of 300-1600 m/z range and select precursor ions using a 3-Th window),
identifying a charge state of the selected precursor ion (para. [0298]: performs a charge-state determination scan of the isolated precursor ions),
reducing the charge state of the selected precursor ion to generate a respective charge-reduced ion at a known m/z ratio (para. [0298]: performs PTR, with reaction time selected according to the determined charge state to produce a single-charge reduction, re-isolate the reduced precursor “based on the predicted charge-state”),
subjecting said charge-reduced ion to fragmentation to generate a plurality of product ions (para. [0298]: subject the re-isolated charge-reduced precursor to trapHCD activation),
performing a mass analysis of the product ions (para. [0298]: performs ion-trap analysis of the resulting products).
Regarding Claim 2:
Coon teaches the method of claim 1. Coon further teaches wherein the step of reducing the charge state of the selected precursor ion comprises subjecting said selected precursor ion to a proton transfer reaction (PTR) (para. [0298]).
Regarding Claim 3:
Coon teaches the method of claim 1. Coon further teaches wherein said precursor ion comprises a peptide ion and, optionally, said peptide ion carries a labeling reagent as a tag (para. [0315]: the experiments use yeast and human peptides carrying TMT tags. Paragraph [0072] also discloses isobarically labeled peptides).
Regarding Claim 5:
Coon teaches the method of claim 1. Coon further teaches wherein the step of reducing the charge state of the selected precursor ion comprises reducing the charge state by one charge unit (paras. [0298 and 0050]: the experiments produce “single-charge reduction.” Paragraph [0050] also expressly states that the precursor charge can be “decreased by 1”).
Regarding Claim 6:
Coon teaches the method of claim 1. Coon further teaches the method further comprising trapping said charge reduced ion in an ion trap prior to subjecting said charge reduced ion to fragmentation (paras. [0296, 0298]: implement the sequence on a stand-alone ion trap, the reduced precursors may be re-isolated in the trap before fragmentation).
Regarding Claim 7:
Coon teaches the method of claim 6. Coon further teaches wherein said fragmentation of the charge reduced ion is achieved in said ion trap by resonantly exciting said charge reduced ion to increase kinetic energy thereof and thereby facilitating its collision-induced fragmentation (para. [0298]: “isolated precursor cations were subjected to resonant-excitation CAD…in the ion trap”).
Regarding Claim 9:
Coon teaches the method of claim 1. Coon further teaches introducing said charge reduced ion into a fragmentation cell (para. [0232]: expressly teaches transfer the isolated charge reduced precursor to the HCD cell for fragmentation).
Regarding Claim 10:
Coon teaches the method of claim 9. Coon further teaches subjecting said charge reduced ion to fragmentation within said fragmentation cell via collision induced dissociation (para. [0232]: the charge-reduced precursor undergoes higher-energy collision inside HCD cell).
Regarding Claim 13:
Coon teaches a method of performing mass spectrometry (Abstract), comprising:
ionizing a sample containing a plurality of peptides tagged with one or more labeling reagents to generate a plurality of tagged peptide ions (paras. [0315, 0295]: provides a sample with yeast and human peptides labeled with TMT tags, ionized and generates precursor ions with a nanoESI source),
selecting precursor peptide ions having an m/z ratio in a target range of m/z ratio from among said tagged peptide ions (para. [0297]: identify a range of m/z (e.g., 300-1600m/z) and selected ions using an isolation window of 3Th),
identifying a charge state of said precursor peptide ions (para. [0298]: performs charge-state determination scan),
reducing the charge state of said precursor peptide ions to generate respective charge-reduced ions at a known m/z ratio (para. [0298]: perform PTR reaction for single charge reduction),
subjecting said charge-reduced ions to fragmentation to generate a plurality of product ions (para. [0298]: the charge-reduced ions undergo trapHCD activation), and
performing a mass analysis of the product ions (para. [0298]: performs mass analysis in the ion trap).
Regarding Claim 14:
Coon teaches the method of claim 13. Coon further teaches wherein said sample comprises different types of peptides (para. [0315]: uses a mixed-organism sample containing different yeast and human peptides).
Regarding Claim 15:
Coon teaches the method of claim 14. Coon further teaches wherein said step of selecting the precursor peptide ions results in co-isolation of different precursor ions (paras. [0005, 0009, 0315]: expressly describes different precursor species being co-isolated within the precursor window).
Regarding Claim 16:
Coon teaches the method of claim 15. Coon further teaches wherein said step of reducing the charge state of the precursor ions results in separating said different precursor ions in m/z space (Abstract and paras. [0231, 0263]: expressly teaches that PTR separates co-isolated precursor species in m/z space. Paragraph [0231] provides the numerical example, co-isolated +2 and +3 ions at 500Th move to 999 and 749.5 Th after PTR).
Claims 17-20 and 22 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US 2017/0205425A1 [hereinafter Yip]
Regarding Claim 17:
Yip teaches a mass spectrometer (Fig. 2 – mass spectrometer 150a), comprising:
an ion source (Fig. 2- electrospray ion source 201) configured to receive a sample and ionize at least a portion of the sample to generate a plurality of analyte ions,
a mass filter (Fig. 2- quadrupole mass filter 208) positioned downstream of said ion source for receiving at least a portion of said analyte ions and being configured to select precursor ions having an m/z ratio in a target range from among said received analyte ions (Fig. 2 and para. [0113]: “A quadrupole mass filter 208 of the mass spectrometer 150a is used in its conventional sense as a tunable mass filter so as to pass ions only within a selected narrow m/z range”),
a charge-reduction device (Fig. 2- C-trap 210) positioned downstream of said mass filter and configured to receive said precursor ions and to cause a reduction in a charge state of at least a portion of said received precursor ions to generate a plurality of respective charge reduced ions at a known m/z ratio (paras. [0122-0124, 0127, 0157]: “the isolated ion population can be stored in either the C-trap or HCD cell for PTR experiments”, where “the subsequent PTR process occurring in the C-trap or HCD cell of the instrument.” Paragraph [0157] further identifies particular reduced products at 833, 917, and 926 Th), and
an ion trap (Fig. 2- multipole ion guide 214) positioned downstream of said charge-reduction device and configured to receive at least a portion of said charged reduced ions (Fig. 2 and paras. [0114]: multipole ion guide 214 serves to guide ions between C-trap 210 and ion trap mass analyzer 216 and also “provides temporary ion storage capability such that ions produced in a first processing step of an analysis method can be later retrieved for processing in a subsequent step”).
Regarding Claim 18:
Yip teaches the mass spectrometer of claim 17. Yip further teaches at least one dissociation device (Fig. 2- high-pressure linear trap cell 217a) positioned downstream of said charge-reduction device for receiving said charge reduced ion and causing dissociation of at least a portion thereof, thereby generating a plurality of product ions (para. [0115]: high-pressure linear trap cell 217a receives ions from guide 214 and “favors ion cooling, ion fragmentation by either collision-induced dissociation or electron transfer dissociation”).
Regarding Claim 19:
Yip teaches the mass spectrometer of claim 18. Yip further teaches a mass analyzer (Fig. 2- low-pressure linear trap cell 217b) positioned downstream of said dissociation device to receive at least a portion of said product ions and generate a mass detection signals indicative of mass-to-charge ratios of said product ions (para. [0115]: “the low-pressure cell 217b favors analytical scanning with high resolving power and mass accuracy”).
Regarding Claim 20:
Yip teaches the mass spectrometer of claim 17. Yip further teaches wherein said charge reduction device comprises a proton transfer reaction (PTR) cell (paras. [0124-0125]: performs photon-transfer charged reduction by mixing precursor cations and reagent anions in the C-trap), and optionally, said PTR cell comprises a first inlet for receiving said selected precursor ions, a second inlet for receiving a reagent for reacting with said precursor ions to cause said charge reduction, and a first outlet through which the charge-reduced ions can exit the PTR cell.
Regarding Claim 22:
Yip teaches the mass spectrometer of claim 18. Yip further teaches wherein said dissociation device comprises a collision cell disposed downstream of said ion trap for receiving the charge-reduced ions from said ion trap and causing fragmentation of at least a portion thereof via collisional dissociation to generate a plurality of product ions (Fig. 2 and paras. [0114-0115]: the high-pressure linear trap cell 217 performs CID and disposed downstream of the multipole ion guide 214 for receiving PTR product ions and cause fragmentations).
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 8, and 11-12 are rejected under 35 U.S.C. 103 as being unpatentable over Coon in view of Yip.
Regarding Claim 8:
Coon teaches the method of claim 7. However, Coon does not expressly teach that wherein said ion trap is maintained at a pressure in a range of about 1 mTorr to about 10 Torr. Yip teaches wherein said ion trap is maintained at a pressure in a range of about 1 mTorr to about 10 Torr (para. [0015]: expressly states that PTR is performed “in the presence of 1mtorr of background gas (i.e., helium)”).
Therefore, it would have been obvious for an ordinary skilled person in the art, before the effective time of filing, to maintain Coon’s ion trap at approximately 1mTorr of helium, as taught by Yip, because Yi explains that helium collision gas removes excess energy generated during PTR and prevents premature fragmentation of the resulting charge-reduced product-ion population ([0015]), thereby stabilizing the charge-reduced ion population before the subsequent fragmentation operation.
Regarding Claim 11:
Coon teaches the method of claim 1. However, Coon does not expressly teach that wherein the charge state of the selected precursor ion is identified based on an isotope profile. Yip teaches wherein the charge state of the selected precursor ion is identified based on an isotope profile (Paras. [0032-0033] teaches “correct computational assignment of charge state to each peak (centroid) in isotopic clusters,” and “making charge determinations based on a distance between individually resolved lines of isotopic clusters.” Paras. [0288 and 0291] further tests each possible charge Z using the expected positions of theoretical isotope peaks and assigns the charge state corresponding to the highest isotope-pattern score).
Therefore, it would have been obvious for an ordinary skilled person in the art, before the effective time of filing, to determine the precursor charge state in Coon using the spacing of the resolved carbon-isotope peaks, as taught by Yip, because Yip explains that comparison of the observed isotope profile with the theoretical isotope-peak positions permits correct computational assignment of the precursor charge state and such an assignment would allow Coon to calculate and accurately re-isolate the expected charge-reduced precursor m/z.
Regarding Claim 12:
Coon in view of Yip teaches the method of claim 11. Yip further teaches wherein said isotope profile comprises a 13C isotope profile (paras. [0288, 0298]: calculates expected isotope-peak positions using a spacing approximately 1.003/Z, and identifies that approximately 1.003-Da value as the mass difference between the carbon-13 and carbon-12 isotopes).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JING WANG whose telephone number is (571)272-2504. The examiner can normally be reached M-F 7:30-17:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert Kim can be reached at 571-272-2293. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JING WANG/Examiner, Art Unit 2881
/WYATT A STOFFA/Primary Examiner, Art Unit 2881
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