DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Amendment
2. Applicant’s amendments, filed 29 June 2026, with respect to the claims have been entered.
Response to Arguments
3. Applicant’s arguments, filed 29 June 2026, with respect to the rejection of claims 1, 2-4, and 14-15 under 35 U.S.C. 102 and 35 U.S.C. 103 have been fully considered and are not full persuasive for the reasons set forth below.
4. Applicant argues on pg. 7 that Badu Tawiah does not disclose the claimed sequential arrangement. Although Badu Tawiah does not explicitly disclose a sequential arrangement, this arrangement is well known in the prior art. Replacing Badu Tawiah’s parallel arrangement with a sequential one would have been obvious to a person of ordinary skill in the art. Badu-Tawiah’s operation relies on delivering a reactive headspace vapor via a nebulizing gas into the electrospray environment. Changing Badu Tawiah’s parallel Swagelok cross to a sequential inline pickup simply changes where the gases mix. See the rejections below for more details.
5. The previous rejections of claims 1-4, and 14-15 under 35 U.S.C. 103 and 35 U.S.C. 102 are withdrawn since the claim scope has changed. Applicant’s amendments to claim 1 have necessitated new grounds of rejection as set forth below.
Claim Rejections - 35 USC § 103
6. 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.
7. 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.
8. Claims 1-4, 15 are rejected under 35 U.S.C 103 as being unpatentable over Badu Tawiah (US 20160329198) in view of Kaufman (US 5247842).
9. Regarding claim 1:
Badu Tawiah teaches an analyzer system, wherein the analyzer system ([0152]-[0153] teaches apparatus for contained-electrospray as in fig. 3, 4. [0165]-[0166] teaches that the apparatus is for ESI-MS analysis of cortisone as shown in fig. 7C) comprises:
at least one mass spectrometry device (“MS” in fig. 3. [0009] teaches that the analyzer can comprise a mass spectrometer) having at least one electrospray ion source nozzle (parts of “ES Emitter” and “Outer Capillary” protruding out of “cross Swagelok element” in fig. 3 form such a nozzle as shown in fig. 4);
at least one liquid supply ([0227] teaches that the contained-electrospray emitter can comprise a cross Swagelok element which enable delivery of a sample through the electrospray ionization emitter liquid reagents. Fig. 3 teaches a spray solvent line feeding into the ES emitter), wherein the at least one liquid supply is configured for providing at least one liquid having at least one analyte ([0007] teaches that the liquid sample comprises a solvent and an analyte. [0166] teaches a mixture consisting of equal aliquots of 10ppm cortisone (MW 360) and 5ppm Girard T reagent at neutral pH);
at least one gas supply ([0003] teaches a carrier gas inlet fluidly connected to the chamber), wherein the at least one gas supply is configured for providing at least one gas ([0227] teaches that the contained-electrospray emitter can comprise a cross Swagelok element which enable delivery of a sample through the electrospray ionization emitter, nebulizer gas); and
at least one dopand gas supply ([0012] teaches injecting a working gas into the working gas inlet. The working gas can comprise an acid. Examples of acids include HCI. In fig. 3, The tube protruding downwards from “cross Swagelok element” and the container for the “HCI” form such a dopand gas supply), wherein the at least one dopand gas supply is configured for providing at least one chemical dopand gas having at least one chemical dopand to the at least one analyte provided by the at least one liquid supply ([0012] teaches contacting the droplet with the working gas and the carrier gas. In some examples, the working gas can comprise an acid, a base, an oxidizer, or a combination thereof. Examples of acids include, but are not limited to, acetic acid, HCl, and combinations thereof. [0027] teaches introducing headspace vapor of HCI, compare fig. 7C to 7A);
wherein the at least one liquid supply and the at least one gas supply are coupled to the at least one mass spectrometry device via the at least one electrospray ion source nozzle (as shown in fig. 3),
wherein the at least one dopand gas supply is connected to the at least one gas supply (fig. 3 shows both the carrier gas (
N
2
) and the reactive vapor (HCI) feeding into the same cross-shaped Swagelok element. The “cross Swagelok element” is part of the gas supply).
Badu Tawiah does not specifically teach that wherein the at least one gas supply and the at least one dopand gas supply are arranged sequentially.
Kaufman teaches an arrangement where a gas supply flows through a liquid container to pick up a vapor prior to reaching the electrospray chamber (col 9 lines 12-25 teaches that air from a supply 140 is directed through a valve 142 to a filter 144. From filter 144, however, the air is provided to a closed container 146 containing a liquid 148. Air exiting the container thus includes a vapor of the liquid. The vapor-containing air proceeds through a controlling orifice 150, and into electrospray chamber 136).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention to have modified Badu Tawiah’s analyzer system in view of Kaufman to arrange the gas supply and the dopant gas supply sequentially and replace Badu Tawiah’s parallel Swagelok cross with Kaufman’s sequential inline mixing. Badu-Tawiah’s operation relies on delivering a reactive headspace vapor via a nebulizing gas into the electrospray environment. Changing Badu Tawiah’s parallel Swagelok cross to Kaufman’s sequential inline pickup simply changes where the gases mix. One of ordinary skill in the art would be motivated to make such modification to enhance the nebulizer and to retard evaporation of the droplets, further reducing the change for droplet disintegration (Kaufman col 3 lines 48-57).
10. Regarding claim 2:
The modified invention above teaches the analyzer system according to claim 1. Badu Tawiah further teaches that wherein the at least one gas supply is a nebulizer gas supply, wherein the nebulizer gas supply is configured for providing at least one nebulizer gas ([0227] teaches that the contained-electrospray emitter can comprise a cross Swagelok element which enable delivery of a sample through the electrospray ionization emitter, nebulizer gas (
e
.
g
.
,
N
2
,
O
2
,
H
e
)
), wherein the at least one nebulizer gas is configured for nebulizing the at least one liquid provided by the at least one liquid supply (Fig. 3 teaches a spray solvent line feeding into the ES emitter. [0152] teaches that the apparatus was created from a cross Swagelok element that allowed three inputs: the sample or spray solvent, N2 nebulizer gas. [0158] teaches that N2 nebulizer gas pressure of 80 psi nebulizes the reaction mixture).
11. Regarding claim 3:
The modified invention above teaches the analyzer system according to claim 1.
Badu Tawiah in one embodiment (fig.3) does not specifically teach that wherein the analyzer system further comprises at least one heated gas supply, wherein the at least one heated gas supply is configured for providing at least one heated gas to the at least one electrospray ion source nozzle.
However, Badu Tawiah in further embodiments and descriptions teaches that wherein the analyzer system further comprises at least one heated gas supply (fig. 7 teaches heated gas on the contained-ES emitter), wherein the at least one heated gas supply is configured for providing at least one heated gas to the at least one electrospray ion source nozzle ([0077] teaches various stimuli: heat. [0186] teaches contained-ES in the presence of acid vapor (HCI) heated to
50
o
C
).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention to have modified Badu Tawiah to include that wherein the analyzer system further comprises at least one heated gas supply, wherein the at least one heated gas supply is configured for providing at least one heated gas to the at least one electrospray ion source nozzle. Such modification would allow for manipulation and control of the droplet reaction environment with a variety of stimuli such as heat (as taught in Badu Tawiah [0225]).
12. Regarding claim 4:
The modified invention above teaches the analyzer system according to claim 1. Badu Tawiah further teaches that wherein the analyte is a steroid or a metabolite thereof ([0157]-[0158] teaches analyzing steroids).
13. Regarding claim 15:
The modified invention above teaches providing at least one analyzer system according to claim 1. Badu Tawiah further teaches a method for analyzing at least one analyte ([0011]-[0012] teaches a method for analyzing analyte), wherein the method comprises:
b) providing the at least one liquid having the at least one analyte and providing the at least one gas to the at least one electrospray ion source nozzle ([0158] teaches a reaction mixture consisting of cortisone and Girard T reagent in methanol/water was electrosprayed. Parts of “ES Emitter” and “Outer Capillary” protruding out of “cross Swagelok element” in fig. 3 form such a nozzle as shown in fig. 4 [0152] teaches that the apparatus was created from a cross Swagelok element that allowed three inputs: (1) the sample or spray solvent, (2) N2 nebulizer gas, and (3) headspace vapor of a reactive gas);
c) providing the at least one chemical dopand gas having the at least one chemical dopand via the at least one gas supply thereby supporting a protonation or a deprotonation of the at least one analyte ([0022] teaches that HCI vapor was introduced into the reaction cavity via the N2 nebulizing gas. [0168] teaches that exposure to headspace vapor of acid or base can modify the pH of the droplets. [0168] teaches that if a mixture of negatively charged protein ions are contained at low pH for a given time, effective protonation can be expected); and
d) conducting at least one measurement with the at least one mass spectrometry device ([0159] teaches that the contained ES MS was recorded after 60s of reaction mixture accumulation be setting the apparatus in front of the mass spectrometer. [0091] teaches that the droplets are then transmitted into the mass spectrometer for analyte characterization).
14. Claim 14 is rejected under 35 U.S.C 103 as being unpatentable over Badu Tawiah in view of Kaufman, further in view of Kobold (US 20170082578).
15. Regarding claim 14:
The modified invention above teaches the analyzer system according to claim 4. Badu Tawiah in view of Kaufman fails to disclose that wherein the at least one analyte is estradiol.
However, Kobold teaches that wherein the at least one analyte is estradiol ([0052]-[0053] teaches that the analyte can be estradiol).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention to have modified Badu Tawiah in view of Kaufman, further in view of Kobold to include that wherein the at least one analyte is estradiol. Such modification would allow for monitoring pharmaceutical active compounds (as taught in [0004]).
Conclusion
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 LARRY LI whose telephone number is (571) 272-5043. The examiner can normally be reached 8:30am-4:30pm. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. 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. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/LARRY LI/
Examiner, Art Unit 2881
/MICHAEL J LOGIE/Primary Examiner, Art Unit 2881
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