DETAILED ACTION
Response to Arguments
Applicant's arguments filed 14 April 2026 have been fully considered but they are not persuasive.
Drawings/specification:
The amendment to the drawings raises new matter issues. See discussion below.
Claim interpretation under 35 USC 112(f)
The amendment to claim 13 provides structure sufficient structure.
Rejections under 35 USC 112:
By amendment the indefiniteness issues and lack of written description rejections have been overcome. However, the amendment raises new issues discussed herein below.
Rejections under 35 USC 102
The remarks take the position that the solvent used to make the amorphous ice on the substrate surface comes from the same initial analyte solution containing the analyte particles. As a result, a separate solvent/vapor source is not needed to provide the solvent to form the amorphous solid. The remarks point to paragraph [0128] of Konijnenberg which teaches adding a second solvent. Therefore suggesting that Konijnenberg fails to disclose “modifying the concentration of solvent in the analyte solution…thereby generating an analyte beam comprising charged analyte particles and molecules of the solvent from the sample solution”
This has been found unpersuasive. Initially, paragraph [0128] was only used as evidence to show that the stream of is of gas phase ions/ion beam. Paragraph [0128] does not require that matrix molecules be separately applied, as the solvent is disclosed to be applied with the molecules ([0037]). However, even if it did, there is no requirement that the solvent used to make the amorphous ice on the substrate surface comes from the same initial analyte solution containing the analyte particles. Therefore, even considering Konijnenberg’s disclosure of a second solvent, it still modifies the concentration of the solvent. That is, claim 1 does not require how the solvent is modified, only that it is modified. Adding an additional solvent would still modify the concentration of the solvent in the analyte solution to generate an analyte beam comprising charged analyte particles and molecules of the solvent from the analyte solution. That is, the claim does not preclude the analyte beam to have more than one solvent.
Similarly, the remarks argue Coon teaches a separate doser. However, again the claim does not preclude modifying the concentration of a solvent with another solvent (i.e. water vapor [0046]). The resultant analyte beam still contains the analyte particles and molecules of the solvent from the analyte solution.
Rejections under 35 USC 103:
The remarks take the position that the combination of Coon and Konijnenberg is the opposite to the disclosure of Coon. This has not been found persuasive. While Coon teaches the vapor stream is generated separately from the generation of analyte particles. Konijnenberg also envisioned an embodiment where a vapor stream is generated separately from the analyte molecules ([0128]). Therefore, the substitution of providing the solvent with the analyte molecules ([0037]) separately ([0128]) was known to Konijnenberg. Additionally, the rationale for such a substitution is discussed in the last office action.
Therefore the remarks have been found unpersuasive. However, since the claim scope has changed, this rejection is currently withdrawn.
Additional notes:
The remarks with respect to claim 13 are not considered as claims 13-20 have been amended to be directed towards a distinct invention. See discussion below.
Election/Restrictions
Newly submitted claims 13-20 directed to an invention that is independent or distinct from the invention originally claimed for the following reasons:
Inventions claims 1-12 and 13-20 are related as process and apparatus for its practice. The inventions are distinct if it can be shown that either: (1) the process as claimed can be practiced by another and materially different apparatus or by hand, or (2) the apparatus as claimed can be used to practice another and materially different process. (MPEP § 806.05(e)). In this case the process as claimed may be performed on a materially different product such as cooling with a cooling block instead of a cold finger (as in Konijnenberg, see paragraph [0148]). Moreover, the product as claimed can practice a materially different process such as providing the analyte source via a mass spectrometer instead of by an ESI alone.
As evidenced by Konijnenberg a cold finger is not necessarily found in a single piece of prior art, therefore leading to undo burden of searching for a specific type of temperature control means. Additionally, since the apparatus is still generic with respect to the analyte source, each analyte source (i.e. ESI/LDI/MS) must be found individually with a cold finger raising undue search burden.
Since applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claims 13-20 are withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Specification
The amendment filed 14 April 2026 is objected to under 35 U.S.C. 132(a) because it introduces new matter into the disclosure. 35 U.S.C. 132(a) states that no amendment shall introduce new matter into the disclosure of the invention. The added material which is not supported by the original disclosure is as follows: Paragraph [0043] “Optionally, a mass spectrometer 7 provides the purified ions and solvent molecules to the analyte source 6”. Specifically, the originally filed disclosure had no suggestion of a mass spectrometer to provide purified ions and solvent molecules to the analyte source 6 with a downstream ESI (seen in figure 7). Paragraph [0043] recites “analyte particles and molecules of the solvent …are collected in an analyte source 6 where they are focused into an analyte beam 13 (such as through electrospray ion deposition). Therefore, the replacement sheet showing MS 7 upstream analyte source 6 would result in a MS followed by analyte source 6 followed by ESI, however the specification is devoid of any suggestion of such an embodiment.
Applicant is required to cancel the new matter in the reply to this Office Action.
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.
Claims 1-12 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.
Claim 1 fails to meet the written description requirement for “performing electrospray ionization (ESI) or laser desorption on the analyte solution, and modifying the concentration of the solvent in the analyte solution to generate a predetermined concentration of the solution”. Specifically, the only disclosure of modifying the concentration of the solvent in the analyte solution to a predetermined concentration is with respect to paragraph [0018] of the originally filed specification which recites:
“In an embodiment, the analyte beam is generated using a mass spectrometer device, wherein particles having a desired mass range, size range, mass-to-charge-ratio range, or combinations thereof, are optionally isolated or purified from the mixture to generate the analyte beam…In a further embodiment, the mass spectrometer is used to enrich, reduce, or alter the solvent in the analyte solution to generate the analyte beam. For example, in an embodiment, the amount or composition of the solvent in the analyte solution is modified to generate a predetermined concentration and/or composition. In an embodiment, the optics of the mass spectrometry device are adjusted to remove excess droplets and solvent clusters. Alternatively, such droplets and solvent clusters are preserved.”
That is, paragraph [0018] teaches a predetermined concentration of the solvent, however the specification is devoid of any specific predetermined concentration. Moreover, paragraph [0018] does not disclose the desired result of the predetermined concentration, thus giving no basis to determine what is considered a predetermined concentration.
MPEP 2163 recites “the written description requirement prevents an applicant from claiming subject matter that was not adequately described in the specification as filed. New or amended claims which introduce elements or limitations that are not supported by the as-filed disclosure violate the written description requirement. ”
Here, the specification does not adequately describe the predetermined concentration nor how it is achieved. Therefore fails to comply with the written description requirement under 112(a).
For the purposes of examination it will be interpreted that any modification of concentration is sufficient to meet the requirement for “predetermined concentration”, as the specification provides no evidence to support possession of a predetermined concentration.
Therefore claim fails to meet the written description requirement under 35 USC 112(a).
Claims 2-12 lack written description by virtue of their dependencies on rejected claim 1.
Claim 12 lacks written description for “removing excess droplets and/or solvent clusters from the analyte beam prior to directing the analyte beam from the mass spectrometer device toward the substrate surface.” Specifically, paragraphs [0018] and [0035] teach “the optics of the mass spectrometry device may be adjusted to remove excess droplets and solvent clusters. Alternatively, such droplets and solvent clusters may be preserved”. However, the specification is silent with respect to how the mass spectrometer optics are adjusted to remove excess solvent. That is, a mass spectrometer separates ions (i.e. charged particles). Excess solvent is not charged, therefore a mass spectrometer is understood by one of ordinary skill in the art to remove uncharged particles via optics. Since the claim is written as a desired result and the specification fails to disclose how that result is achieved, claim 12 fails to meet the written description requirement under 35 USC 112(a). MPEP 2163 recites “the written description requirement prevents an applicant from claiming subject matter that was not adequately described in the specification as filed. New or amended claims which introduce elements or limitations that are not supported by the as-filed disclosure violate the written description requirement. ”
Here, the claim 12 is not adequately described as to how the mass spectrometer removes excess solvent.
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 10-12 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 10 is vague and indefinite for reciting “the analyte beam comprising the charged analyte particles and molecules of the solvent from the analyte solution generated using the mass spectrometer device”. Specifically, claim 1 already requires performing ESI or LDI to generate “an analyte beam comprising charged analyte particles and molecules of the solvent from the analyte solution”. It is not clear how both the ESI/LDI and the mass spectrometer can generate the ions. No unambiguous determination can be made.
For the purposes of examination, it will be interpreted that the ESI mass spectrometer generates the ions. It is noted that claim 1 does not require the mass spectrometer, so in this case it is interpreted that claim 10 is directed to a different disclosed embodiment where ESI MS is used instead of ESI alone.
Claims 11-12 are vague and indefinite by virtue of their dependencies on rejected claim 10.
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)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-2, 4-5 and 7-10 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Konijnenberg et al. (US pgPub 2023/0280245) as evidenced by Mark (Mark, “how small is a water molecule”, 2018) alone or further as evidenced by Chen (US pgPub 2023/0307222).
Regarding claim 1, Konijnenberg et al. teach a method for depositing an analyte on a substrate ([0039] teaches gas phase ions surrounded by a frozen solvent upon impact with a cryogenically cooled carrier substrate to form a non-continuous layer. In light of the instant specification the analyte particles are ions ([0016] of the published application). That is analyte (ions) are deposited on a substrate) comprising the steps of:
a) forming an analyte solution comprising analyte particles and a solvent ([0037] before ionization receiving one or more molecules dissolved in a solvent, wherein the molecules become charged (i.e. ionized). Paragraph [0039] teaches these ions become the sample, thus analytes);
b) performing ESI on the analyte solution ([0056]) and modifying the concentration of the solvent in the analyte solution to generate a predetermined concentration of the solution ([0037] molecules are dissolved in solvent and then [0056] electrospray ionization is performed. Since ESI inherently requires a solvent (see [0004] of Chen et al. US pgPub 2023/0307222), the concentration of solvent is modified by ESI. Alternatively, [0128] adding an additional solvent (i.e. in addition to the solvent added in [0037]-[0038]) would adjust the concentration. The adjusted concentration is interpreted to be the predetermined concentration, as the instant specification fails to disclose any suggestion as to what is considered a predetermined concentration), thereby generating an analyte beam from the analyte solution comprising charged analyte particles and molecules of the solvent from the analyte solution ([0037]-[0038] generating gas phase ions comprising a solvation shell which is solvent molecules arranged around the gas phase ion. Paragraph [0128] clarifies that the gas phase ions are an ion beam [0037]-[0038]. Note, since the solvation shell is formed as discussed in paragraphs [0037]-[0038] the gas phase ions comprise the molecules of the solvent from the analyte solution applied in paragraphs [0037]-[0038]);
c) directing the analyte beam toward a substrate surface (as seen in figure 1, ions from ESI source 20/22 are directed towards carrier substrate 160 having a major surface for receiving ions thereon ([0130])) at atmospheric pressure or under a vacuum ([0105] teaches deposition chamber 140 (containing carrier 160) is under vacuum and receives ions from the electrospray ionization source 20. ) such that the charged analyte particles and molecules of the solvent impinge on the substrate surface (fig. 1 shows carrier substrate 160 inside chamber 140 and paragraph [0130] teaches carrier substrate has a major surface for receiving ions (i.e. from electrospray source 20)),
wherein the substrate surface is at a temperature of 0°C or less thereby forming an amorphous solid layer of the solvent on the substrate surface ([0186] teaches a temperature less than 250 K or -23.15 degrees C. paragraph [0046] teaches ice growth rate is less than one monolayer per hour. Since the conditions of the claim are identical to that of Konijnenberg et al., it is interpreted that the monolayer of ice is an amorphous solid layer. As evidenced from paragraph [0015] of the published application rapid cooling results in amorphous solids. In Konijnenberg, the solvent is frozen by cryogenic temperatures thus resulting in the amorphous solid by rapid cooling),
wherein the amorphous solid layer has a thickness of 10 microns or less ([0046] teaches ice growth rate of less than one monolayer per hour wherein a monolayer is a gap free layer of molecules having a thickness of one molecule resulting the ice growth may be substantially zero (i.e. less than 10 microns1). That is, ice layer is nearly zero thus less than 10 microns), and wherein the charged analyte particles are embedded within the deposited amorphous solid layer (solvation shell see paragraph [0038], thus ions (i.e. analytes) are embedded in the shell when frozen).
Regarding claim 2, Konijnenberg et al. teach wherein the substrate surface is at a temperature of -1000C or less ([0186] teaches preferably less than 80 degrees K or -193.15 degrees C).
Regarding claims 4-5, Konijnenberg et al. teach wherein the solvent is water ([0038]).
Regarding claim 7-8, Konijnenberg et al. teach wherein the analyte beam is directed towards the substrate under vacuum, wherein the charged analyte particles and molecules of the solvent contact the surface at a pressure less than 10-3 Torr ([0016] teaches gas phase ions are received at the substrate at a pressure less than 10-5 mbarr or ~7-5 Torr).
Regarding claim 9, Konijnenberg et al. teach wherein the amorphous solid layer has a thickness of 5 microns or less (a monolayer is less than 5 microns).
Regarding claim 10, Konijnenberg et al. teach wherein the analyte solution comprising the analyte particles and solvent is inserted into a mass spectrometry device ([0056] teaches ESI may form part of an ESI MS), the analyte beam comprising the charged analyte particles and the molecules of the solvent from the analyte solution is generated using the mass spectrometer device (when ESI is part of the MS, the unit together forms charged analyte particles as discussed above in claim 1), wherein generating an the analyte beam further comprises performing mass spectrometry analysis on a mixture of particles and isolating particles from the mixture based on the mass, size, mass-to-charge ratio, or combinations thereof (inherent to a mass spectrometer).
Claims 1, 3, 6 and 10-11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Coon (US pgPub 2020/0158607) as evidenced by Chen (US pgPub 2023/0307222).
Regarding claim 1, Coon et al. teach a method for depositing an analyte on a substrate ([0054] teaches deposition of analyte particles) comprising the steps of:
a) forming an analyte solution comprising analyte particles and a solvent ([0054] teaches concomitantly with the collection of analyte particles, the molecular water beam is used to encase the analyte particles in amorphous ice. Concomitantly means occurring at the same time2. Therefore, a solution of analyte and solvent is formed by encasing molecular particles prior to deposition on the substrate);
b) performing ESI on the analyte solution ([0045], wherein as evidenced by Chen (US pgPub 2023/0307222) is evidence that ESI requires the use of spray formed by solvent to ionize the samples [0004]) and modifying the concentration of the solvent in the analyte solution to generate a predetermined concentration of the solution (by addition of water vapor [0046] (i.e. solvent) the solvent of the analyte solution is modified), thereby generating an analyte beam from the analyte solution ([0046] teaches molecular beam 14 are transported along the same axis as travelled by the analyte beam 13, thus when concomitantly applied the analyte beam is formed) comprising charged analyte particles and molecules of the solvent from the analyte solution (water vapor ([0046]) and analyte beam via ESI [0046]);
c) directing the analyte beam toward a substrate surface at atmospheric pressure or under a vacuum such that the charged or uncharged analyte particles and molecules of the solvent impinge on the substrate surface ([0045] initial formation of ice followed by solvent encased analyte particles from analyte beam and molecular beam concurrently applied. That is, the solvent encased analyte particle beam impinges the surface of the substrate),
wherein the substrate surface is at a temperature of 0°C or less thereby forming an amorphous solid layer of the solvent on the substrate surface ([0054] teaches formation of amorphous ice and paragraph [0055] teaches -175C),
wherein the amorphous solid layer has a thickness of 10 microns or less ([0026]), and wherein the charged or uncharged analyte particles are embedded within the deposited amorphous solid layer ([0054]).
Regarding claim 3, Coon et al. teach wherein the analyte beam is an ion beam formed using laser desorption (laser desorption, see paragraph [0013]).
Regarding claim 6, Coon teaches wherein the substrate is an EM grid comprising a continuous film or membrane positioned across a top or bottom surface of the EM grid ([0055] graphene oxide support film supported by cupper or gold grids).
Regarding claim 10, Coon teaches wherein the analyte solution comprising the analyte particles and solvent is inserted into a mass spectrometry device ([0013] teaches mass spectrometer isolates or purifies the analyte ions, thus is generated by isolation. Paragraph [0022] teaches ESI and MS, wherein ESI requires the use of solvent as discussed above), the analyte beam comprising the charged analyte particles and the molecules of the solvent from the analyte solution is generated using the mass spectrometer device (when ESI part of MS, the unit together forms charged analyte particles as discussed above in claim 1), wherein generating an the analyte beam further comprises performing mass spectrometry analysis on a mixture of particles and isolating particles from the mixture based on the mass, size, mass-to-charge ratio, or combinations thereof (inherent to a mass spectrometer).
Regarding claim 11, Coon teaches wherein generating an analyte beam comprises isolating particles having a mass-to-charge-ratio within 2 m/z to the desired analyte particles (([0015] teaches purified or isolated to a purity of 99%. The instant specification teaches identical language in paragraph [0017] of the published application. Since the purity of 99% of the mass spectrometer of the instant specification is sufficient to result in isolation of 2 m/z to preselect desired analyte particles ([0019]of the instant published application), the modified ms of Coon is inherently capable of 2 m/z isolation).
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 12 is rejected under 35 U.S.C. 103 as being unpatentable over Coon or Konijnenberg et al. and further in view of Heifje et al. (US pgPub 2005/0035283)
Regarding claim 12, Coon or Konijnenberg teaches directing the analyte beam from the spectrometer device toward the substrate surface (Coon [0013], Konijnenberg, [0056]).
However, neither reference suggests removing excess solvent prior to exiting MS.
However, Heifje et al. teaches removing excess solvent prior to exiting MS ([0044] teaches drying excess solvent from ESI plume thus removing excess prior to exit MS).
Since both inventions are directed towards introducing a sample and solvent into a mass spectrometer, it would have been obvious to dry the excess solvent from the ESI plume because it would achieve greater sensitivity ([0044]).
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
US2025/0060292 to Coon et al. is available as prior art under 35 USC 102(a)(2) and fully anticipates at least claims 1 and 13. This reference may be precluded from use by invoking an exception under 102(b)(2)(c).
US 2024/0319054 to Benner similarly teaches cryo-EM sample preparation using an ESI source and a DMA.
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 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
1 As evidenced by “How small is a water molecule” a water molecule is .000282 microns in diameter, therefore a monolayer of single molecules is well under 10 microns.
2 The American heritage dictionary defines concomitant as “occurring or existing concurrently”. Definition attached herewith.
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