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 .
Election/Restrictions
Applicant’s election without traverse of inventive group III in the reply filed on 11/24/25 is acknowledged.
Claims 1-20, 22-25, 33-34, 37-39, and 44-51 are withdrawn.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
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.
Claim 43 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 43 recites, “wherein the one or more amino acid additives include at least one of L-serine, D-serine, or amino acid additives or L- or D-configuration.” The list of possible amino acid additives includes “amin acid additives.” It is unclear what is meant by this limitation, as such, the claim is indefinite.
Claims 41-43 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. Claim 41 recites, “electrolyte with neutral pH.” It is unclear whether “neutral” is being used to mean exactly neutral, e.g., 7.00, or if it encompasses a range or pH at and around 7, e.g., 6.5-7.5. The specification provides little guidance, and no examples of neutral pH electrolytes. Since one of ordinary skill in the art cannot discern the metes and bounds of this limitation, it makes the claim at issue indefinite.
Claim Rejections - 35 USC § 103
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 21, 26-28, 30-32, 35-36, and 40-41 are rejected under 35 U.S.C. 103 as being unpatentable over US 2015/0048255 A1 [Jarrell] in view of Kristoff, Courtney J., et al. "Low flow voltage free interface for capillary electrophoresis and mass spectrometry driven by vibrating sharp-edge spray ionization." Analytical chemistry 92.4 (2020): 3006-3013 [Kristoff]
Regarding Claim 21:
Jarrell teaches an apparatus, comprising:
a separation capillary having an injection end and a distal end, the injection end configured to receive analyte liquid and the distal end configured to expel the analyte liquid (Fig. 1 capillary near (104) marker);
an acoustic probe capillary having a probe end and an inlet end, the probe end of the acoustic probe capillary configured to vibrate and positioned in contact with the distal end of the separation capillary (Fig. 1 (105) below (111), which is vibrated by piezoelectric element (111)), the acoustic probe capillary carrying a fluid from the inlet end to the probe end (as shown in Fig. 1).
However, Jarrell fails to specify a ground terminal positioned at the distal end of the separation capillary. Rather, Jarrell discusses grounding capillary (105), which positioned at the distal end of separation capillary (104). Paras 23, 25.
Kristoff describes a vibrating sharp edge ion source (abstract, et al), and teaches using a ground terminal on the distal end of a separation capillary. Fig. 1A inset below, Interface Design and Implementation. It would have been obvious to one of ordinary skill in the art before the effective time of filing to place the ground terminal taught by Kristoff on the grounded capillary (105) of Jarrell, and at the distal end of separation capillary. One would have been motivated to do so since this would provide a well-understood and effective technique for achieving the grounding required in Jarrell.
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Regarding Claim 26:
The above modified invention teaches the apparatus of claim 21, wherein a flow rate of the fluid in the acoustic probe capillary is less than one microliter per minute. It is unclear what structure is implied by a flow rate of a capillary, and the specification does not appear to associate any particular capillary with this flow rate. As such, the limitation is interpreted to be a non-limiting intended use. Further, the structure of the modified invention is at least capable of achieving 0 flow rate, which falls within the claimed range.
Regarding Claim 27:
The above modified invention teaches the apparatus of claim 21, but fails to specify that the separation capillary has a length, measured between the injection end and the distal end, between 5 cm and 2 m.
A change in length, with nothing more, is an obvious modification to the separation capillary. See In re Rose, 220 F.2d 459, 105 USPQ 237 (CCPA 1955) (Claims directed to a lumber package "of appreciable size and weight requiring handling by a lift truck" were held unpatentable over prior art lumber packages which could be lifted by hand because limitations relating to the size of the package were not sufficient to patentably distinguish over the prior art.); In re Rinehart, 531 F.2d 1048, 189 USPQ 143 (CCPA 1976) ("mere scaling up of a prior art process capable of being scaled up, if such were the case, would not establish patentability in a claim to an old process so scaled." 531 F.2d at 1053, 189 USPQ at 148.).
It the instant case, Jarrell teaches a capillary, but makes no mention of its length. In light of the above noted precedent, it would have been obvious to one of ordinary skill in the art before the effective time of filing to modify the capillary of Jarrell to be between 5cm to 2 m from its injection end and the distal end. This would have been obvious because changing the length of a capillary amounts to merely scaling up or down a prior art capillary that could easily be adjusted to any desired size. Such adjustments are well within the skill of a person of ordinary skill in the art, and can be made for the users’ preferences or convenience.
Regarding Claim 28:
The above modified invention teaches the apparatus of claim 21, but fails to specify that
the separation capillary has a total volume of no more than 8 micro-liters.
A change in volume, with nothing more, is an obvious modification to the separation capillary. See In re Rose, 220 F.2d 459, 105 USPQ 237 (CCPA 1955) (Claims directed to a lumber package "of appreciable size and weight requiring handling by a lift truck" were held unpatentable over prior art lumber packages which could be lifted by hand because limitations relating to the size of the package were not sufficient to patentably distinguish over the prior art.); In re Rinehart, 531 F.2d 1048, 189 USPQ 143 (CCPA 1976) ("mere scaling up of a prior art process capable of being scaled up, if such were the case, would not establish patentability in a claim to an old process so scaled." 531 F.2d at 1053, 189 USPQ at 148.).
It the instant case, Jarrell teaches a capillary, but makes no mention of its volume. In light of the above noted precedent, it would have been obvious to one of ordinary skill in the art before the effective time of filing to modify the capillary of Jarrell to volume of no more than 8 micro-liters. This would have been obvious because changing the volume of a capillary amounts to merely scaling up or down a prior art capillary that could easily be adjusted to any desired size. Such adjustments are well within the skill of a person of ordinary skill in the art, and can be made for the users’ preferences or convenience.
Regarding Claim 30:
The above modified invention teaches the apparatus of claim 21, wherein an inner diameter of the separation capillary is between 15 micrometers to 35 micrometers. Jarrell Claim 8.
Regarding Claim 31:
The above modified invention teaches the apparatus of claim 21, wherein a distance between the distal end of the separation capillary and the ground terminal is less than 2 millimeters. The modified invention of claim 21 places the ground terminal at the distal end of the separation capillary, i.e. 0 mm away.
Regarding Claim 32:
The above modified invention teaches the apparatus of claim 21, wherein a flow rate of the analyte liquid in the separation capillary is between 0 nano-liters and 70 nano-liters.
It is unclear what structure is implied by a flow rate of a capillary, and the specification does not appear to associate any particular capillary with this flow rate. As such, the limitation is interpreted to be a non-limiting intended use. Further, the structure of the modified invention is at least capable of achieving 0 flow rate, which falls within the claimed range.
Regarding Claim 35:
The above modified invention teaches the apparatus of claim 21, wherein the analyte liquid includes small or large molecules that are positively charged, negatively charged, or neutral charged.
The claim is directed to an apparatus, and said apparatus has a capillary with an “injection end configured to receive analyte liquid.” The above claim looks to specify what the analyte is; however, the analyte is still not positively claimed as part of the apparatus. As such, in that the apparatus of the modified invention is configured to receive a liquid sample, it is also configured to receive a particular liquid sample, including a liquid that includes small or large molecules that are positively charged, negatively charged, or neutral charged.
Regarding Claim 36:
The above modified invention teaches the apparatus of claim 21, wherein the analyte liquid includes cationic proteins and acidic background electrolytes.
The claim is directed to an apparatus, and said apparatus has a capillary with an “injection end configured to receive analyte liquid.” The above claim looks to specify what the analyte is; however, the analyte is still not positively claimed as part of the apparatus. As such, in that the apparatus of the modified invention is configured to receive a liquid sample, it is also configured to receive a particular liquid sample, including a liquid that includes cationic proteins and acidic background electrolytes.
Regarding Claim 40:
The above modified invention teaches the apparatus of claim 21, wherein the analyte liquid includes anionic or neutral proteins and an electrolyte buffer at a pH of above 7.
The claim is directed to an apparatus, and said apparatus has a capillary with an “injection end configured to receive analyte liquid.” The above claim looks to specify what the analyte is; however, the analyte is still not positively claimed as part of the apparatus. As such, in that the apparatus of the modified invention is configured to receive a liquid sample, it is also configured to receive a particular liquid sample, including a liquid that includes anionic or neutral proteins and an electrolyte buffer at a pH of above 7.
Regarding Claim 41:
The above modified invention teaches the apparatus of claim 21, wherein the fluid in the acoustic probe capillary is an electrolyte with neutral pH.
Kristoff teaches using an electrolyte in a acoustic probe capillary, wherein the electrolyte flowing through the capillary is near-neutral pH ammonium acetate having a pH of 6.5. Separation and Detection with CE-VSSI-MS compared to CE-UV. Such a near-neutral pH would reasonably be considered a neutral pH in the context of mass spectrometry.
It would have been obvious to one of ordinary skill in the art before the effective time of filing to use the neutral pH electrolyte of Kristoff in the above modified invention. One would have been motivated to do so since Kristoff teaches its use in the context of vibration-based ionization and testing.
Claims 42-43 are rejected under 35 U.S.C. 103 as being unpatentable over US 2015/0048255 A1 [Jarrell] in view of Kristoff, Courtney J., et al. "Low flow voltage free interface for capillary electrophoresis and mass spectrometry driven by vibrating sharp-edge spray ionization." Analytical chemistry 92.4 (2020): 3006-3013 [Kristoff] as applied above, and further in view of Clarke, David J., and Dominic J. Campopiano. "Desalting large protein complexes during native electrospray mass spectrometry by addition of amino acids to the working solution." Analyst 140.8 (2015): 2679-2686 [Clarke]
Regarding Claims 42-43:
The above modified invention teaches the apparatus of claim 41, but fails to teach that the fluid in the acoustic probe capillary includes L-serine.
Clarke teaches adding L-serine to spray solution to reduce the adverse effects of sodium adduction to proteins. Abstract. It would have been obvious to one of ordinary skill in the art before the effective time of filing to further modify Jarrell by adding L-serine to spray solution, as is taught by Clarke. One would have been motivated to do so in order to reduce the adverse effects of sodium adduction to proteins in native mass spectra.
Claims 29 is rejected under 35 U.S.C. 103 as being unpatentable over US 2015/0048255 A1 [Jarrell] in view of Kristoff, Courtney J., et al. "Low flow voltage free interface for capillary electrophoresis and mass spectrometry driven by vibrating sharp-edge spray ionization." Analytical chemistry 92.4 (2020): 3006-3013 [Kristoff] as applied above, and further in view of US 2021/0082677 A1 [Li].
Regarding Claim 29:
The above modified invention teaches the apparatus of claim 21, but fails to teach that a voltage difference is maintained between the injection end of the separation capillary and the ground terminal.
Li teaches a vibrating sharp edge spray ionization system (abstract) maintaining a voltage different between an injection end of the separation capillary and a ground terminal (see annotated Fig. 7 below, between High voltage sample and ground terminal) in order to provide capillary electrophoresis of the sample to the spray end (paras 126-128). It would have been obvious to one of ordinary skill in the art before the effective time of filing to modify Jarrell to maintain a voltage difference between the injection end of the separation capillary and the ground terminal, as is taught by Li. One would have been motivated to do so in order to realize the capillary electrophoresis sample flow taught by Li.
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Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to WYATT A STOFFA whose telephone number is (571)270-1782. The examiner can normally be reached M-F 0700-1600 EST.
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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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WYATT STOFFA
Primary Examiner
Art Unit 2881
/WYATT A STOFFA/Primary Examiner, Art Unit 2881