DETAILED ACTION
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 13 May 2026 has been entered.
Response to Arguments
Applicant’s arguments with respect to claim(s) 1-12 and 14-18 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
With respect to the rejection of Bloomfield in view of Baba, it is noted the remarks suggest that Baba does not cure the deficiencies of Bloomfield. This has been found unpersuasive. Specifically, Bloomfield teaches two different dissociation techniques (i.e. increasing aggressive fragmentation). Moreover, Bloomfield teaches in paragraph [0061] “the systems and methods described herein are not limited to using collision energies of a CID method. Increasingly more aggressive values of a fragmentation parameter of any fragmentation method can be used. For example, increasingly more aggressive radio frequency (RF) excitations of an RF dissociation method can be used, or increasingly more aggressive electron energies of an electron capture dissociation (ECD) method can be used.”
That is, while Bloomfield only teaches increasingly more aggressive values of a fragmentation parameter for CID, RF dissociation or ECD, one of ordinary skill in the art would recognize that the method is applicable to “any fragmentation method”. Baba, clearly teaches a fragmentation method that uses CID and ExD and provides the advantage that using two fragmentation techniques provides for better identification. Baba modifies Bloomfield by suggesting another fragmentation method (CID and ExD), which would also be suitable for increasingly more aggressive values of a fragmentation parameter because Bloomfield already suggests that these parameters may be increasingly aggressive separately. Therefore, it would have been obvious to substitute the single fragmentation device of Bloomfield for the individually selectable dual fragmentation device of Baba ([00160]-[00161]) because it would improve identification of the sample. Moreover, Bloomfield is evidence that the method was suitable to improve any fragmentation methods ([0061] of Bloomfield) such as the dual fragmentation suggested in Baba.
The substitution would result in both CID and ExD for each specified cycle time with increasingly aggressive fragmentation.
Therefore, the claims stand rejected as discussed herein below.
Claim Interpretation
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
This application includes one or more claim limitations that do not use the word “means,” but are nonetheless being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, because the claim limitation(s) uses a generic placeholder that is coupled with functional language without reciting sufficient structure to perform the recited function and the generic placeholder is not preceded by a structural modifier. Such claim limitation(s) is/are:
“one or more dissociation devices that perform at least two different orthogonal dissociation techniques” in claim 1.
Because this/these claim limitation(s) is/are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it/they is/are being interpreted to cover the corresponding structure described in the specification as performing the claimed function, and equivalents thereof.
If applicant does not intend to have this/these limitation(s) interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitation(s) to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph (e.g., by reciting sufficient structure to perform the claimed function); or (2) present a sufficient showing that the claim limitation(s) recite(s) sufficient structure to perform the claimed function so as to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph.
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 9 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 9 is vague and indefinite for reciting: “wherein the at least two different dissociation techniques include one or more of electron-based dissociation (ExD), ultraviolet photodissociation (UVPD), infrared photodissociation (IRMPD), and collision-induced dissociation (CID).”
That is, claim 1 now requires two orthogonal dissociation techniques. Therefore it is not clear how one of ExD UVPD, IRMPD or CID could fulfill the requirement for two “orthogonal dissociation techniques” as now required by claim 1. Indeed most of the remarks filed 13 May 2026 concede this point. Stating “each of these [[i.e. CID, RF dissociation and ECD]] describes tuning one parameter of one dissociation method, not the use of two orthogonal techniques…orthogonal dissociation techniques, as the applicant’s specification explains, are techniques that use “a different mechanism of dissociation or fragmentation know to produce different types of fragments than the first technique used”.
That is, since the remarks take the position that a single technique does not fall under “orthogonal techniques”, then claim 9 cannot also fall under the orthogonal techniques as any one of ExD UVPD, IRMPD or CID is not an orthogonal technique as understood by the applicant’s specification and expressly argued by the remarks.
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 1-4, 6-12 and 14-18 is rejected under 35 U.S.C. 103 as being unpatentable over Bloomfield (US pgPub 2018/0012742) in view of Baba (WO 2019186322) (submitted with DIS of 03 May 2022).
Regarding claim 1, Bloomfield teaches a system (figs. 7-8) for performing at least two different dissociation techniques in a data-independent acquisition (DIA) mass spectrometry experiment ([0063] teaches a tandem mass spectrometry DIA experiment with different values for a fragmentation parameter. Paragraph [0061] teaches the fragmentation parameter provides increasingly more aggressive values such as RF excitation or increasingly more aggressive electron energies for ECD. The different fragmentation parameter values are interpreted to be two different dissociation techniques because the first parameter value fragments minimal amounts of ions of the ion beam, wherein the one or more additional values have increasingly aggressive values that produce increasingly more fragmentation of the ions in the ion beam ([0069]). In other words, the first fragmentation parameter is a different dissociation technique from the second fragmentation parameter because different RF excitation or electron energy results in increased fragmentation (i.e. first technique = minimal fragmentation, second technique = increased fragmentation). Note: under the BRI, the instant claims only require a single dissociation device, therefore changing the operational parameters to result in different quantities of product ions is within the scope of different dissociation techniques specifically because the claim does require how the techniques are different. Moreover, paragraph [0088] teach the at least to different dissociation techniques performed by one or more dissociation devices include one or more of ExD…CID. That is, as understood by the instant specification different techniques may be the same dissociation technique (i.e. CID only different in some way, for instance the parameters of the dissociation).), comprising:
an ion source (710) device that ionizes compounds of a sample, producing an ion beam ([0065]); and
a tandem mass spectrometer (720) that includes:
a mass filter device ([0066] teaches the tandem mass spectrometer includes one or more physical mass filters),
one or more dissociation devices that perform at least two different dissociation techniques ([0070] teaches tandem mass spectrometer 720 performs fragmentation and paragraph [0069] teaches two or more values for a fragmentation parameter. Paragraph [0061] teaches fragmentation by CID or ECD, thus either a CID or ECD device, wherein the two different dissociation techniques are the varied fragmentation parameter), and
a mass analyzer (inherent to tandem MS) that: receives the ion beam from the ion source device (as seen in figure 7), and
a processor (730) in communication with tandem mass spectrometer that divides a specified precursor ion mass-to-charge ratio (m/z) range of the ion beam into a first set of two or more precursor ion mass selection windows and divides the precursor ion m/z range of the ion beam into a second set of two or more precursor ion mass selection windows ([0071] at step 810 in figure 8. Note while only one set of windows is shown, the instant published specification teaches at paragraph [0093] “first set 801 and second set 802 are actually the same set of three precursor ion mass selection windows. As a result, only one set of three precursor ion mass selection windows is actually used in this case”. Therefore, the first and second set are interpreted to be the same set shown in figure 8 of Bloomfield. Alternatively, interpreting the first four windows at 810 to be the first set and the subsequent two windows to be the second set),
wherein the processor (730) provides operational instructions to the tandem mass spectrometer ([0068]) which causes the tandem mass spectrometer to perform the DIA mass spectrometry experiment on the specified precursor ion m/z range ([0069]) by:
executing a series of cycles (fig. 8, 830 paragraph [0071] “In step 830, for each precursor ion isolation window of the two or more precursor ion isolation windows, tandem mass spectrometer 720 of FIG. 7 fragments the precursor ions in the precursor ion isolation window for each of the two or more values for the fragmentation parameter, producing a product ion spectrum for each value”. That is, each “CE1”-“CE3” is interpreted to be a cycle), each cycle having a cycle time ([0073] teaches for each of the two or more values for the fragmentation parameter “a time series of combined product ion spectra is produced”. That is each CE1-CE3 of figure 8 has a cycle time defined by windows at 810. See also figure 9, t1-Tn and paragraph [0074]), wherein the specified precursor ion m/z range is scanned each cycle (an m/z range is divided into two or more isolation windows in 810 and each window is fragmented at the different fragmentation energies [0071]) and each cycle corresponds to one of a plurality of portions of a retention time dimension (inherent as CE1-CE3 are sequentially performed, see also figure 9 t1-tn and time series. Note: LC is performed [0051] wherein sample introduction occurs over time thus each cycle corresponds to a retention time dimension of the LC), wherein each cycle of the series of cycles includes selecting, dissociating and mass analyzing each window of both the first and second set (since the first and second set are interpreted to be the same set (see above), each cycle (CE1-CE3) includes selecting dissociating and mass analyzing each window see paragraph [0071]. Alternatively, interpreting the first four windows to be the first set and the subsequent two windows to be the second set);
within a specified cycle time (cycle time is the divided windows of 810 over the m/z range—see also t1-tn in figure 9), select each precursor ion mass selection window of the first set using the mass filter device (CE1 in figure 8 shows fragmentation of selected precursor ion mass selection windows divided in step 810.. Paragraph [0074] teaches mass filtering of the m/z range), dissociate the each window of the first set using a first dissociation technique of the at least two different dissociation techniques performed by the one or more dissociation devices (CE1 is the first fragmentation parameter (dissociation technique) resulting in less fragments as discussed above, CE1 performed for each window as seen in figure 8 and [0071]), and mass analyze product ions generated from the dissociation of the each window of the first set using the mass analyzer, producing product ion intensity and m/z measurements for the each window of the first set (each product ion intensity/m/z measurement for each window for CE1 seen in figure 8, thus necessitating dissociation of each window of the first set of windows 810 and mass analyzing the product ions),
within the specified cycle time (cycle time is the divided windows of 810 over the m/z range—see also t1-tn in figure 9), select each precursor ion mass selection window of the second set using the mass filter device (CE2 in figure 8 shows fragmentation of selected precursor ion mass selection windows divided in step 810.. Paragraph [0074] teaches mass filtering of the m/z range), dissociate the each window of the second set using a second dissociation technique of the at least two different dissociation techniques performed by the one or more dissociation devices (CE2 is the second fragmentation parameter (dissociation technique) resulting in more fragments as discussed above, CE2 performed for each window as seen in figure 8 and [0071]), and mass analyze product ions generated from the dissociation of the each window of the second set using the mass analyzer, producing product ion intensity and m/z measurements for the each window of the second set (each product ion intensity/m/z measurement for each window for CE2 seen in figure 8, thus necessitating dissociation of each window of the first set of windows 810 and mass analyzing the product ions),
combine the product ion intensity and m/z measurements for the each window of the first set with the product ion intensity and m/z measurements for the each window of the second set ([0056] teaches spectra of each of the three different energies can be combined over the isolation windows), and
analyze the combined measurements to identify or quantitate the compounds of the sample (paragraph [0004] teaches the product ion spectrum can be used to identify a molecule of interest and the intensity of one or more product ions can be used to quantitate the amount of the compound present in the sample).
While Bloomfield teaches any method of fragmentation may be used and calls out CID and ECD separately ([0061]), Bloomfield fails to disclose the two different dissociation techniques are orthogonal.
However, Baba teaches the two different dissociation techniques are orthogonal. (abstract note sample precursor ion is fragmented and analyzed twice).
Baba modifies Bloomfield by suggesting two fragmentations of a precursor ion by two different devices instead of using just CID or ECD as suggested in Bloomfield. In otherwords, during each specified cycle time the ions would undergo both CID and ECD. Note: Baba similar to Bloomfield suggests a mass filter (i.e. isolation device 115 in figure 14) that selects at least one precursor ion from an ion beam, fragments using the second fragmentation device 125 and mass analyzes the product. Then the mass isolation device again selects the at least one precursor ion for fragmentation via a first fragmentation device (see paragraphs [00160]-[00161]). In otherwords, Bloomfield teaches a number of cycles (CE1-CE3) which the precursor (mass window) is selected for increasing aggressive fragmentation. Baba also teaches the ability to select the same precursor for different types of fragmentation, thus suitable for the fragmentation method of Bloomfield (i.e. the only modification to the method of Bloomfield would be using different fragmentation techniques in CE1 and CE2 or as in Baba the same precursor ion(s) are twice fragmented by different fragmentation devices via action of the mass filter and processor control).
Since both devices are directed towards fragmenting ions of a m/z ratio using different dissociation techniques, it would have been obvious to one of ordinary skill in the art to use the CID and ExD devices of Baba to perform the first and second dissociation techniques of Bloomfield because combining the different dissociation techniques results in improved identification when glycoprotein identification is desired ([0024]) as compared with only using CID or ExD where glycan information is lost or there is an insufficient database to identify glycans using ExD ([0021] and [0023] respectively).
Regarding claim 2, Bloomfield teaches wherein the tandem mass spectrometer further, within the cycle time, selects the precursor ion m/z range using the mass filter device ([0074] teaches mass filtering of the m/z range for each time t1-tn (i.e. isolation windows)), transmits precursor ions of the precursor ion m/z range from the mass filter device to the mass analyzer using the one or more dissociation devices (Q1 to fragmentation or dissociation device to form product ion spectrum ([0074])), and mass analyzes the transmitted precursor ions using the mass analyzer, producing precursor ion intensity and m/z measurements for the precursor ion m/z range (fig. 9, intact precursor ion intensity traces [0076] at CE1, wherein CE1 causes minimal fragmentation see [0084]).
Regarding claim 3, Bloomfield teaches wherein the first set and the second set are the same set (810 see figure 8).
Regarding claim 4, Bloomfield teaches wherein the first set and the second set have different numbers of precursor ion mass selection windows (in the alternative interpretation above, first set has four windows, second set has two).
Regarding claim 6, Bloomfield teaches wherein windows of the first set have different m/z ranges than windows of the second set (in alternative interpretation, windows divided by m/z range ([0071]) thus second set has different m/z ranges than first set).
Regarding claim 7, Bloomfield teaches wherein each window of the first set is selected, dissociated, and mass analyzed before each window of the second set is selected, dissociated, and mass analyzed (in alternative interpretation first four windows are analyzed before the last two).
Regarding claim 8, Bloomfield teaches wherein at least one window of the second set is selected, dissociated, and mass analyzed after a first window of the first set is selected, dissociated, and mass analyzed and before a second window of the first set is selected, dissociated, and mass analyzed (interpreting every other window to belong to a different set).
Regarding claim 9, Bloomfield teach the at least two different dissociation techniques include ExD or CID ([0061]).
Regarding claim 10, Bloomfield teaches wherein the one or more dissociation devices comprise one dissociation device and the one dissociation device performs the first dissociation technique and the second dissociation technique (CID by changing fragmentation parameters or ECD by changing fragmentation parameters ([0061])).
Regarding claim 11, Bloomfield only discloses a single dissociation device and therefore fails to disclose wherein the one or more dissociation devices comprise a first dissociation device and a second dissociation device and the first dissociation device performs the first dissociation technique and the second dissociation device performs the second dissociation technique.
However, Baba teaches wherein the one or more dissociation devices comprise a first dissociation device and a second dissociation device and the first dissociation device performs the first dissociation technique and the second dissociation device performs the second dissociation technique (abstract note sample precursor ion is fragmented and analyzed twice).
Baba modifies Bloomfield by suggesting two fragmentations of a precursor ion by two different devices instead of using just CID or ECD as suggested in Bloomfield..
Since both devices are directed towards fragmenting ions of a m/z ratio using different dissociation techniques, it would have been obvious to one of ordinary skill in the art to use the CID and ExD devices of Baba to perform the first and second dissociation techniques of Bloomfield because combining the different dissociation techniques results in improved identification when glycoprotein identification is desired ([0024]) as compared with only using CID or ExD where glycan information is lost or there is an insufficient database to identify glycans using ExD ([0021] and [0023] respectively).
Regarding claim 12, Bloomfield teaches wherein the product ion intensity and m/z measurements for the each window of the first set are analyzed separately from the product ion intensity and m/z measurements for the each window of the second set in order to identify or quantitate the compounds of the sample (each analysis at each fragmentation parameter occurs separately as indicated in figures 8-9 and combination to identify/quantitate as suggested in paragraph [0004] and [0056]).
Claim 14 is directed to the method of claim 1 and is commensurate in scope. Therefore, claim 14 is obvious for the same reasons discussed above.
Claim 15 is directed to the method of claim 1 and is commensurate in scope. Therefore, claim 15 is obvious for the same reasons discussed above. Moreover, Bloomfield teaches a computer program product, comprising a non-transitory and tangible computer-readable storage medium whose contents include a program with instructions being executed on a processor ([0019]).
Claim 16 is broader in scope than claim 1 and taught as discussed herein above.
Regarding claim 17, Bloomfield teaches wherein the retention time dimension is defined by an elution separation system ([0051]).
Regarding claim 18, Bloomfield teaches wherein the elution separation system is liquid chromatography ([0051]).
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 5 is rejected under 35 U.S.C. 103 as being unpatentable over Bloomfield in view of Applicant admitted prior art (US pgPub 2023/005727 )
Regarding claim 5, Bloomfield fails to teach wherein windows of the first set have different windows widths than windows of the second set.
However, AAAPA teaches wherein windows of the first set have different windows widths than windows of the second set ([0028] note windows can have variable widths).
AAPA modifies Bloomfield by suggesting variable width windows.
Since both inventions are directed towards DIA, it would have been obvious to one of ordinary skill in the art to adopt the variable length windows of AAPA in the device of Bloomfield because it AAPA is evidence that either the same width or variable widths will lead to predictable results ion mass selection or isolation window spans ([0028]). (Note MPEPE 2143 (I) (B)).
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
US 20170213713 to Green teaches switching between ETD and CID and creating windows via a filter (figs 1-2 and paragraphs [0167]-[0171])
JP2009068981 teaches sequential use of ECD and CID (see figure 1)
Data independent acquisition during a signal cycle is additionally known to at least:
US-20180240658—fig. 2, [0059]
WO-2017037563, WO2017033087—two or more mass selection windows during each cycle
US-20200234936—[0052] ion mass selection windows is selected than fragmented during each cycle.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHAEL J LOGIE whose telephone number is (571)270-1616. The examiner can normally be reached M-F: 7:00AM-3:00PM.
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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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/MICHAEL J LOGIE/Primary Examiner, Art Unit 2881
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