DETAILED ACTION
This Office action is in response to the amendment filed on July 1st, 2026. Claims 1, 3-4, 6-12, 14-18, and 22-23 are pending.
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(a)
Claims 3 & 14 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 3 & 14 now recite “setting a threshold difference based on the one or more operation parameters of the DMS”. The method as disclosed in the original disclosure selects the operation parameters based on the threshold difference, not the threshold difference based on the operation parameters (see for example fig. 12, step 1222). Examiner can find no mention in the original disclosure of a method of setting the threshold “based on the one or more operation parameters”.
Claim Rejections - 35 USC § 112(b)
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, 3-4, 7-11, and 22-23 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential steps, such omission amounting to a gap between the steps. See MPEP § 2172.01. The omitted steps are: the actual calculation of the alpha function (modeling of data as an equation, curve fitting operations).
Claims 1, 3-4, 6-11, and 22-23 recite a method of calculating the first alpha function which comprises the setting and adjustment of voltages in a DMS and the generation of a sample plot. No calculation step for calculating the alpha function (modelling an equation based on the plot) is included, therefore it is unclear how the claimed method can result in calculating the first alpha function. Claim 6 recites a transformation step that results in the first alpha function and is therefore not rejected on these grounds.
Claim 6 is 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 6 recites “transforming the sample plots into the first alpha function.” It is unclear how the sample plots are transformed into the first alpha function.
Claims 3 & 14 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.
Claims 3 & 14 recite “setting a threshold difference based on the one or more operation parameters of the DMS”. It is unclear how the threshold different is set “based on the operation parameters”, particularly given that the operation parameters are not determined until it is after the comparison to the threshold. For the purposes of comparison to the prior art, examiner will simply ignore the “based on the operation parameters” clause and look to see if the arts set a threshold difference and determine a range of separation field values based on threshold.
Claims 12 and 15-18 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 claims recite determining parameters “to achieve sufficient separation of the first compound and the second compound”. It is unclear how much separation would be considered “sufficient”. Claim 14 specifies that sufficient separation is determined based on a threshold alpha function and therefore not rejected based on these grounds.
Claim Rejections - 35 USC § 102
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.
Claim(s) 12 and 15-18 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US 2018/0328934 (Campbell et al.).
Regarding claim 12, Campbell et al. discloses an automated method of operating a mass spectrometer (MS) comprising a differential mobility spectrometer (DMS), the automated method comprising:
(a) analyzing a first compound, wherein analyzing a first compound comprises: introducing the first compound to the DMS at each of a plurality of separation voltages (SVs); while introducing the first compound at each of the plurality of SVs, adjusting a compensation voltage (CoV) of the DMS; while adjusting the CoVs for each of the plurality of SVs, concurrently monitoring an analytical signal from the MS; based at least in part on monitoring the analytical signal, identifying a CoV optimum for each of the plurality of SVs and generating a first mathematical function based at least in part on the CoV optimum for each of the plurality of SVs, wherein the first mathematical function has an input comprising a SV-related parameter and an output value comprising a CoV-related parameter (fig. 9-10);
(b) analyzing a second compound, wherein analyzing a second compound comprises: introducing the second compound to the DMS at each of a plurality of separation voltages (SVs); while introducing the second compound at each of the plurality of SVs, adjusting a compensation voltage (CoV) of the DMS; while adjusting the CoVs for each of the plurality of SVs, concurrently monitoring an analytical signal from the MS; based at least in part on monitoring the analytical signal, identifying a CoV optimum for each of the plurality of SVs; and generating a second mathematical function based at least in part on the CoV optimum for each of the plurality of SVs, wherein the second mathematical function has an input comprising a SV-related parameter and an output value comprising a CoV-related parameter (fig. 9-10); and
(c) determining operation parameters of the DMS to achieve sufficient separation of the first compound and the second compound, based on the first mathematical function and the second mathematical function, wherein the operation parameters of the DMS comprise a range of separation field values of the DMS (“maximum separation occurring at various CoV/SV settings, with SV voltages of about 2500 to about 4000 volts, demonstrating varying separation between the functional group substitutions at the 5-, 6-, and 7-positions” P 67).
Regarding claim 15, Campbell et al. discloses the automated method of claim 12, subtracting the first mathematical function from the second mathematical function to determine a difference function; identifying a global maximum in an absolute value of the difference function; and determining a separation field value associated with the global maximum (“maximum separation occurring at various CoV/SV settings, with SV voltages of about 2500 to about 4000 volts, demonstrating varying separation between the functional group substitutions at the 5-, 6-, and 7-positions” P 67).
Regarding claim 16, Campbell et al. discloses the automated method of claim 12, wherein the SV-related parameter is one of the SV and a separation field, and wherein the CoV-related parameter is one of the CoV and a compensation field (fig. 9-10).
Regarding claim 17, Campbell et al. discloses the automated method of claim 13, setting a test separation field of the DMS with the range of separation field values; and introducing a test sample to the DMS, wherein the test sample comprises at least one of the first compound and the second compound (“adjusting at least one of a compensation voltage and a separation voltage of the differential mobility spectrometer to maximize transmission therethrough of one species of the ionized labeled analytes relative other species of the ionized labeled analytes.” P 7).
Regarding claim 18, Campbell et al. discloses the automated method of claim 12, further comprising ionizing the first compound and the second compound prior to introducing the first compound and the second compound to the DMS (“Ions 102 (e.g., ionized labeled analytes) can be generated by an ion source (not shown)” P 46).
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, 3-4, 6-10, & 22-23 is/are rejected under 35 U.S.C. 103 as being unpatentable over “Characterization of narcotics using differential mobility spectrometry” (Pavlacka et al.).
Regarding claim 1, Pavlacka et al. discloses an automated method of operating a mass spectrometer (MS) comprising a differential mobility spectrometer (DMS), the automated method comprising:
introducing a first compound to the DMS (“To calculate specific alpha coefficients, sets of measured data are shown in Table 2.”);
calculating a first alpha function for the first compound (“α2 and α4 can be calculated based on experimentally obtained values of CV and RF voltage. α2 and α4 coefficients can be then calculated by systems of equations where only α2 and α4 are unknown parameters”);
introducing a second compound to the DMS (“To calculate specific alpha coefficients, sets of measured data are shown in Table 2.”);
calculating a second alpha function for the second compound (“α2 and α4 can be calculated based on experimentally obtained values of CV and RF voltage. α2 and α4 coefficients can be then calculated by systems of equations where only α2 and α4 are unknown parameters”); and
determining one or more operation parameters of the DMS to achieve separation of the first compound and the second compound, based on the first alpha function and the second alpha function (“at RF = 1480 V, where the biggest differences of position of product ion peak were observed.”);
wherein calculating the first alpha function and the second alpha function comprise:
setting a separation voltage (SV) of the DMS (“RF was applied from 500 to 1500 V.”);
adjusting a compensation voltage (CoV) of the DMS (“Values of compensation voltage were swept from −40 to +15 V in 0.28 V steps.”);
while adjusting the CoV, concurrently monitoring an analytical signal from the MS; and based at least in part on monitoring the analytical signal, generating a sample plot for each of a plurality of different separation voltage settings of the DMS, wherein each sample plot comprises a mass spectrometer signal intensity versus the CoV (“To calculate specific alpha coefficients, sets of measured data are shown in Table 2.”),
wherein the operation parameters of the DMS comprise a range of separation field values of the DMS (“at RF = 1480 V, where the biggest differences of position of product ion peak were observed.”, note that examiner is interpreting “range” to include the possibility of a single value, based on claim 4 which determines a range as a single value).
Pavlacka et al. does not disclose determining whether there is sufficient separation by comparing the difference between the first alpha function and the second alpha function to a threshold alpha function difference.
Thresholding is a well-known method of determining when a value is large enough for the intended purpose, and it would have been obvious to a person having ordinary skill in the art at the time the application was filed to modify the method Pavlacka to determine the acceptable range of separation field values by taking those values for which a difference between the first alpha function and the second alpha function being equal to or larger than a threshold because the alpha function difference is a known measure of the separation of the ion peaks in CoV, and this ensure the peaks are separated to some minimal level needed for discrimination.
Regarding claim 3, Pavalcka et al. discloses the automated method of claim 1, further comprising: setting a threshold alpha function difference (inherent in the claim 1 limitation of making the determination “based on” the threshold difference – the threshold difference must be set in order to be used in the determination) based on the one or more operation parameters of the DMS (cannot be evaluated), and determining a range of separation field values for which an absolute value of a difference between the first alpha function and the second alpha function is equal to or larger than a threshold alpha function difference (this is merely a restatement of the claim 1 limitation to determining the range of separation values “based on” whether the difference is equal to or larger than a threshold difference).
Regarding claim 4, Pavlacka et al. discloses the claimed invention except for subtracting the first alpha function from the second alpha function to determine a difference function; identifying a global maximum in an absolute value of the difference function; and determining a separation field value associated with the global maximum. Finding global maximums is a well-known analytical technique, and it would have been obvious to a person having ordinary skill in the art at the time the application was filed to modify the method of Pavlacka et al. to determine the separation field this way because the alpha function difference is a known measure of the separation of the ion peaks in CoV, and the global maximum would ensure the biggest difference in ion peaks, as Pavalacka is designed to do (“at RF = 1480 V, where the biggest differences of position of product ion peak were observed.”), even in the case where the separation field at the global maximum is not one of the values directly for the calculation of the alpha function.
Regarding claim 6, Pavlacka et al. discloses the automated method of claim 1 further comprising transforming the sample plots into the first alpha function (“Summary of nonlinear alpha function for all measured narcotics is summarized in Table 3.”).
Regarding claim 7, Pavlacka et al. discloses the automated method of claim 1, further comprising: setting a test separation field of the DMS within the range of separation field values; and introducing a test sample to the DMS, wherein the test sample comprises at least one of the first compound and the second compound (“Five common illicit drugs were analyzed by DMS in the temperature range of 75–120 °C (amplitudes from 500 to 1500 V for the separation voltage), at RF = 1480 V, where the biggest differences of position of product ion peak were observed.”).
Regarding claim 8, Pavlacka et al. discloses the automated method of claim 1, further comprising ionizing the first compound and the second compound prior to introducing the first compound and the second compound to the DMS (“To calculate specific alpha coefficients, sets of measured data are shown in Table 2.”, where ionization is inherent in measurement with DMS).
Regarding claim 9, Pavlacka et al. discloses the automated method of claim 8, further comprising introducing with the first compound a DMS transport gas comprising at least one of nitrogen and nitrogen with a chemical modifier (“Dried air purified by activated carbon and dewatered by molecular sieve was used as a carrier gas.”, where nitrogen is a major component of air).
Regarding claim 10, Pavlacka et al. discloses the automated method of claim 8, further comprising setting a composition of the DMS transport gas prior to ionizing the first compound (“Dried air purified by activated carbon and dewatered by molecular sieve was used as a carrier gas.”).
Regarding claim 22, Pavlacka et al. discloses automated method of operating a mass spectrometer (MS) comprising a differential mobility spectrometer (DMS), the automated method comprising:
introducing a first compound to the DMS (“To calculate specific alpha coefficients, sets of measured data are shown in Table 2.”);
calculating a first alpha function for the first compound (“α2 and α4 can be calculated based on experimentally obtained values of CV and RF voltage. α2 and α4 coefficients can be then calculated by systems of equations where only α2 and α4 are unknown parameters”);
introducing a second compound to the DMS (“To calculate specific alpha coefficients, sets of measured data are shown in Table 2.”);
calculating a second alpha function for the second compound (“α2 and α4 can be calculated based on experimentally obtained values of CV and RF voltage. α2 and α4 coefficients can be then calculated by systems of equations where only α2 and α4 are unknown parameters”);
introducing a third compound to the DMS (“To calculate specific alpha coefficients, sets of measured data are shown in Table 2.”);
calculating a third alpha function for the third compound (“α2 and α4 can be calculated based on experimentally obtained values of CV and RF voltage. α2 and α4 coefficients can be then calculated by systems of equations where only α2 and α4 are unknown parameters”),
wherein calculating the first alpha function, the second alpha function, and the third alpha function comprises:
setting a separation voltage (SV) of the DMS (“RF was applied from 500 to 1500 V.”);
adjusting a compensation voltage (CoV) of the DMS (“Values of compensation voltage were swept from −40 to +15 V in 0.28 V steps.”);
while adjusting the CoV, concurrently monitoring an analytical signal from the MS; and based at least in part on monitoring the analytical signal, generating a sample plot for each of a plurality of different separation voltage settings of the DMS, wherein each sample plot comprises a mass spectrometer signal intensity versus the CoV (“To calculate specific alpha coefficients, sets of measured data are shown in Table 2.”),
Pavlacka et al. does not disclose subtracting the first alpha function from the second alpha function to determine a first difference function; subtracting the first alpha function from the third alpha function to determine a second difference function; subtracting the second alpha function from the third alpha function to determine a third difference function; identifying a threshold alpha function difference; and determining a separation field value such that an absolute value of the first difference function, an absolute value of the second difference function, and an absolute value of the third difference function are equal to or greater than the threshold alpha function difference.
Thresholding is a well-known method of determining when a value is large enough for the intended purpose, and it would have been obvious to a person having ordinary skill in the art at the time the application was filed to modify the method Pavlacka to determine the acceptable range of separation field values by taking those values for which an absolute value of a differences between the functions being equal to or larger than a threshold alpha function difference because the alpha function difference is a known measure of the separation of the ion peaks in CoV, and this ensure the all 3 peaks are separated to some minimal level needed for discrimination.
Regarding claim 23, Pavalacka et al. discloses the automated method of claim 22, wherein the threshold alpha function difference is an alpha function difference sufficient to separate any two of the first compound, the second compound, and the third compound (intended result of the already claimed thresholding, and therefore non-limiting, see MPEP 2111.04, ‘However, the court noted that a "‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’" Id. (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)).’).
Claim(s) 11 is/are rejected under 35 U.S.C. 103 as being unpatentable over (Pavlacka et al.) as applied to claim 8 above, and further in view of US 2018/0328934 (Campbell et al.).
Regarding claim 11, Pavlacka et al discloses the automated method of claim 8, further comprising introducing the first compound with the DMS transport gas comprising nitrogen (“Dried air purified by activated carbon and dewatered by molecular sieve was used as a carrier gas.”, where nitrogen is a major component of air).
Pavlacka et al. does not disclose the transport gas comprising a first amount of nitrogen with a first amount of the chemical modifier, and a second amount of nitrogen with a second amount of the chemical modifier. Campbell et al. discloses a method of operating a mass spectrometer comprising a differential mobility spectrometer where a first compound is introduced discretely with the DMS transport gas comprising nitrogen, a first amount of nitrogen with a first amount of the chemical modifier (fig. 9-10). It would have been obvious to a person having ordinary skill in the art at the time the application was filed to modify the method of Pavlacka et al. to include the chemical modifier of Campbell et al. to vary the separation between compounds to ensure better discrimination, as disclosed by Campbell (“In some cases, this can increase the separation between analytes labeled with different labels.”). It would further has been obvious to discreetly introduce with first and second amounts of chemical modifier and gas to determine the alpha function in various configurations.
Claim(s) 14 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2018/0328934 (Campbell et al.).
Regarding claim 14, Campbell et al. discloses the claimed invention except for setting a threshold alpha function difference based on the one or more operation parameters of the DMS, and determining a range of separation field values for which an absolute value of a difference between the first mathematical function and the second mathematical function being equal to or larger than a threshold mathematical function difference. Thresholding is a well-known method of determining when a value is large enough for the intended purpose, and it would have been obvious to a person having ordinary skill in the art at the time the application was filed to modify the method Campbell et al. to determine the acceptable range of separation field values by taking those values for which an absolute value of a difference between the first and second functions being equal to or larger than a threshold function difference to ensure the peaks are separated to some minimal level needed for discrimination.
Response to Arguments
Applicants’ arguments filed July 1st, 2026 have been fully considered but they are not persuasive.
Regarding the 112(b) rejection of claims 12 and 15-18 because it is unclear how much separation would be sufficient; applicant notes that the application describes a variety of methods in which sufficient separation can be determined including a comparison of the difference of alpha functions to a threshold and determination of a separation value associated with a global maximum difference.
Regarding the comparison of the difference of alpha functions to a threshold, this is not claimed in claims 12 and 15-18, so the claims are not limited to this. Regarding determination of the global maximum separation, this determines the operating parameters that would result in the largest possible separation but does not guarantee that that this largest possible separation is “sufficient”. Applicant themselves point this out when discussing the prior art Pavlacka (see applicant’s remarks “While Pavlacka states that the biggest differences of position of product ion peak were observed at an RF value of 1480V, nowhere does Pavlacka discuss a threshold difference nor whether the RF value of 1480V met such a threshold difference.”).
Regarding the 112(b) rejection of claim 6, applicant argues that a person having ordinary skill in the art would understand how to transform a given plot or function into another plot or function and gives examples of adjusting a point or points of the given plot via addition, subtraction, multiplication, and the like.
The examples applicant gives in their argument merely adjust the values, they do not transform the plot of values into a function, which is an equation that takes inputs and gives outputs, a very different animal from a plot of specific values. To transform a plot into a function some form of curve fitting must be performed to transform the set of points into a model that can be described with an equation or set of equations. Based on the specification, it appears applicants intend to model the data using a Taylor series with coefficients determined through curve fitting (see applicant’s paragraphs 45-48); therefore the claim should be amended to specify the steps involved in transforming the plot into an equation such as the one in paragraph 47.
Regarding the rejection of claim 1 over Pavlacka et al., applicant argues that Pavlacka only discloses finding the maximum separation and does not compare the alpha function to a threshold difference to determine if there is sufficient separation.
Examiner agrees, which is why she rejected this aspect (originally in claim 3 rather than claim 1) under 103 and not 102. Applicant has not argued that the difference would not be obvious or attacked examiner’s line of reasoning for rejecting under 103.
Regarding claim 12, applicant states that “Claim 12 includes similar recitations and is patentable under section 102 for at least similar reasons.”
Examiner is not sure what similar recitations applicant is referring to, as the only limitation of claim 1 they argue, that of comparing the alpha function difference to a threshold, is not present in claim 12. Claim 12 is based on an alternative method of determining parameters based on finding an optimal difference without knowing the alpha functions and requiring the use of ramps at multiple separation voltages, as described for example with respect to applicant’s figures 8-11.
Regarding claim 22, applicant states that “Claim 22 includes similar recitations and is patentable under section 103 for at least similar reasons.”
Claim 22 does include similar recitations, but again examiner rejected on 103 grounds, and applicant has only argued that the limitation is not found in the primary art. They have not argued any reason it is not obvious.
Conclusion
THIS ACTION IS MADE FINAL. 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 ELIZA W OSENBAUGH-STEWART whose telephone number is (571)270-5782. The examiner can normally be reached 10am - 6pm Pacific Time M-F.
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/ELIZA W OSENBAUGH-STEWART/Primary Examiner, Art Unit 2881
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