DETAILED ACTION
Drawings
The drawings are objected to under 37 CFR 1.83(a). The drawings must show every feature of the invention specified in the claims. Therefore, the mass spectrometer of claim 10 and the modified mass spectrometer of claims 17-18 must be shown or the feature(s) canceled from the claim(s). No new matter should be entered.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
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.
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 10-20 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 10 fails to meet the written description requirement for requiring the result of “identifying desired analyte particles within the mixture, and isolating the desired analyte particles from the mixture based on the mass, size, mass-to-charge ratio, or combinations thereof, of the desired analyte particles”. MPEP 2163.03 recites:
“While there is a presumption that an adequate written description of the claimed invention is present in the specification as filed. In re Wertheim, 541 F.2d 257, 262, 191 USPQ 90, 96 (CCPA 1976), a question as to whether a specification provides an adequate written description may arise in the context of an original claim. An original claim may lack written description support when (1) the claim defines the invention in functional language specifying a desired result but the disclosure fails to sufficiently identify how the function is performed or the result is achieved”
Here, the only discussion of how identification of desired analyte particles and the isolation of the identified desired analyte particles is the exact language in paragraph [0018]. Because the instant specification provides no disclosure as to how the identification is performed nor of how that identification is used to effect isolation based on the claimed parameters, the specification fails to demonstrate the applicant was in possession of the claimed invention.
Moreover, paragraph [0005] of the instant published application recites that computational resources are required to analyze the data. Therefore, one of ordinary skill in the art would recognize that the identification is via a computer. MPEP 2161.01 recites:
“Similarly, original claims may lack written description when the claims define the invention in functional language specifying a desired result but the specification does not sufficiently describe how the function is performed or the result is achieved. For software, this can occur when the algorithm or steps/procedure for performing the computer function are not explained at all or are not explained in sufficient detail (simply restating the function recited in the claim is not necessarily sufficient). In other words, the algorithm or steps/procedure taken to perform the function must be described with sufficient detail so that one of ordinary skill in the art would understand how the inventor intended the function to be performed.”
Here, because the algorithm, flow charts, prose, procedure is absent to the disclosure as to how the inventor intends to achieve the identification function, claim 10 fails to meet the written description requirement. As further recited in MPEP 2161.01 (I):
It is not enough that one skilled in the art could write a program to achieve the claimed function because the specification must explain how the inventor intends to achieve the claimed function to satisfy the written description requirement. See, e.g., Vasudevan Software, Inc. v. MicroStrategy, Inc., 782 F.3d 671, 681-683, 114 USPQ2d 1349, 1356, 1357 (Fed. Cir. 2015).
Therefore, claim 10 fails to meet the written description requirement
Claims 11-12 fail to meet the written description requirement by virtue of their dependencies thereon.
Claim 13 lacks written description for requiring a temperature control means. “a temperature control means” invokes 35 USC § 112(f), however the disclosure is devoid of any structure, material or acts that perform the claim structure. MPEP 2163.03 (VI) recites:
“A claim limitation expressed in means- (or step-) plus-function language "shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof." 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. If the specification fails to disclose sufficient corresponding structure, materials, or acts that perform the entire claimed function, then the claim limitation is indefinite because the applicant has in effect failed to particularly point out and distinctly claim the invention as required by 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph. In re Donaldson Co., 16 F.3d 1189, 1195, 29 USPQ2d 1845, 1850 (Fed. Cir. 1994) (en banc). Such a limitation also lacks an adequate written description as required by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph, because an indefinite, unbounded functional limitation would cover all ways of performing a function and indicate that the inventor has not provided sufficient disclosure to show possession of the invention”
Because the unbounded functional limitation of “temperature control means” would cover all ways of performing temperature control, the specification fails to provide sufficient disclosure to show possession of a temperature control means.
Claims 14-20 and 10-12 fail to meet the written description requirement by virtue of their dependencies on claim 13.
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 10-20 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 requiring “a mass spectrometer device, wherein generating an analyte beam comprises performing mass spectrometry” Specifically, claim 10 is dependent upon claim 17 which already requires “a modified mass spectrometer” to provide ions and molecules of the solvent to the analyte source. Moreover, claim 17 is dependent upon claim 13 which requires, in part, “the analyte source is able to produce…an analyte beam comprising charged or uncharged analyte particles and molecules of a solvent”. Initially, it is not clear whether the analyte beam defined in claim 10 is the same or different from the analyte beam defined in claim 13, which claim 10 indirectly depends therefrom. Moreover, it is not clear whether the step of performing mass spectrometry of claim 10 is performed by the defined mass spectrometer device of claim 10 or by the modified mass spectrometer of claim 17. No unambiguous determination can be made. It appears from the specification that there is only one mass spectrometer (see for instance paragraph [0036]). For the purposes of examination it will be interpreted that the defined mass spectrometer device of claim 10 is referring to the modified mass spectrometer of claim 17.
Further claim 10 recites the limitation “identifying desired analyte particles within the mixture, and isolating the desired analyte particles from the mixture based on the mass, size, mass-to-charge ratio, or combinations thereof, of the desired analyte particles” is vague and indefinite because the claim does not provide a discernable boundary on what performs the function. The recited function does not follow from the structure recited in the claim i.e. the mass spectrometer of claim 10, the modified mass spectrometer of claim 17 or any of the structural components of the apparatus of claim 13, so it is unclear whether the function requires some other structure or is simply a result of operating the claimed structural components in a certain manner. Thus, one of ordinary skill in the art would not be able to draw a clear boundary between what is and is not covered by the claim. See MPEP 2173.05(g) for more information.
Claims 11-12 are vague and indefinite by virtue of their dependencies on rejected claim 10.
Claim 13 is vague and indefinite fore reciting temperature control means. The claim limitation “temperature control means” invokes 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. However, the written description fails to disclose the corresponding structure, material, or acts for performing the entire claimed function and to clearly link the structure, material, or acts to the function. The disclosure is devoid of any structure that performs the function of the claim Therefore, the claim is indefinite and is rejected under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph.
Applicant may:
(a) Amend the claim so that the claim limitation will no longer be interpreted as a limitation under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph;
(b) Amend the written description of the specification such that it expressly recites what structure, material, or acts perform the entire claimed function, without introducing any new matter (35 U.S.C. 132(a)); or
(c) Amend the written description of the specification such that it clearly links the structure, material, or acts disclosed therein to the function recited in the claim, without introducing any new matter (35 U.S.C. 132(a)).
If applicant is of the opinion that the written description of the specification already implicitly or inherently discloses the corresponding structure, material, or acts and clearly links them to the function so that one of ordinary skill in the art would recognize what structure, material, or acts perform the claimed function, applicant should clarify the record by either:
(a) Amending the written description of the specification such that it expressly recites the corresponding structure, material, or acts for performing the claimed function and clearly links or associates the structure, material, or acts to the claimed function, without introducing any new matter (35 U.S.C. 132(a)); or
(b) Stating on the record what the corresponding structure, material, or acts, which are implicitly or inherently set forth in the written description of the specification, perform the claimed function. For more information, see 37 CFR 1.75(d) and MPEP §§ 608.01(o) and 2181.
The term “enriching, reducing, or altering the solvent” in claim 12 is a relative term which renders the claim indefinite. The term “enriching, reducing, or altering” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Specifically, except for the exact recitation in the specification, there is no disclosed standard as to by what degree.
Claims 14-20 and 10-12 are vague and indefinite by virtue of their dependencies on claim 13.
The term “modified mass spectrometer” in claim 17 is a relative term which renders the claim indefinite. The term “modified” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Here, the instant disclosure only suggests that the mass spectrometer is modified, however is devoid in any discussion as to how it is modified. Therefore one of ordinary skill in the art would not be reasonably apprised of the scope of such a modification.
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 1-5, 7-9, 13-15, 17 and 19-20 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)
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) generating an analyte beam 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), where the analyte beam comprises charged or uncharged analyte particles and molecules of the solvent ([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 or uncharged 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 or uncharged 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 claim 3, Konijnenberg et al. teach wherein the analyte beam is an ion beam formed using ESI (fig. 1, ESI 20).
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 or uncharged 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 13, Konijnenberg et al. teach a sample preparation system (fig. 1) comprising:
a) a vacuum chamber or gas chamber (140);
b) a substrate (160) positioned with the vacuum chamber or gas chamber (160 is within 140), wherein said substrate comprises a receiving surface ([0130] teaches 160 has a major surface for receiving ions);
c) a temperature control means able to provide a temperature of 0°C or less to the receiving surface of the substrate ([0148] cryogenic cooling system 600 in figure 8 cools the substrate 160, paragraph [0186] to a temperature less than 80 K); and
d) an analyte source (20 or alternatively output of the mass spectrometer to vacuum chamber 140) in fluid communication with the vacuum chamber or gas chamber (20 is in communication with 140 via mass spectrometer), wherein the analyte source is able to produce a controllable analyte beam comprising charged or uncharged analyte particles and molecules of a solvent (20 produces an analyte beam with solvent ([0037]-[0039]), which is controllable via the mass spectrometer including a filter 70 see paragraph [0107]), and direct said analyte beam to contact the receiving surface of the substrate ([0037]-[0039]).
Regarding claim 14, Konijnenberg et al. teach wherein the analyte source is able to generate an ion beam using electrospray ionization (ESI) or laser desorption (fig. 1, ESI 20).
Regarding claim 15, Konijnenberg et al. teach wherein the temperature control means is able to provide a temperature of -100°C or less to the receiving surface of the substrate (see discussion with respect to claim 2 above).
Regarding claim 17, Konijnenberg et al. teach a modified mass spectrometer (fig. 1 mass spectrometer) device able to provide ions and molecules of the solvent to the analyte source (syringe pump 21 to pump a solution of one or more molecules into the emitter 22 of the ESI 20 ([0104]), wherein the solution includes a solvent and ions [0037]. For this interpretation the analyte source is interpreted to be the output of the mass spectrometer).
Regarding claim 19-20, Konijnenberg et al. teach wherein the analyte beam is directed towards the substrate under vacuum, wherein the charged or uncharged 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).
Claims 1, 6, 13 and 16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Coon (US pgPub 2020/0158607).
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) generating an analyte beam ([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) from the analyte solution (concomitant analyte encased by molecular beam ), where the analyte beam comprises charged or uncharged analyte particles and molecules of the solvent (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 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 13, Coon et al. teach a sample preparation system (fig. 1) comprising:
a) a vacuum chamber or gas chamber (1);
b) a substrate (probe 2 holds sample plate [0045]) positioned with the vacuum chamber or gas chamber (2 is within 1), wherein said substrate comprises a receiving surface (surface that the analyte beam 13 is directed towards of sample plate [0045]);
c) a temperature control means ([0024] teaches temperature control means) able to provide a temperature of 0°C or less to the receiving surface of the substrate ([0044] teaches the temperature is maintained using a coolant, thus controlling the temperature. Paragraph [0011] and [0055] teaches amorphous ice is formed at a temperature of -175 degrees C ([0055]) and that the temperature at the surface of the substrate is -175 ([0011])); and
d) an analyte source (6/4 see second figure) in fluid communication with the vacuum chamber or gas chamber (as seen in figures 1-2), wherein the analyte source is able to produce a controllable analyte beam comprising charged or uncharged analyte particles and molecules of a solvent ([0054] analyte particles encased in molecular water, controllable by mass spectrometer), and direct said analyte beam to contact the receiving surface of the substrate (as seen in figure 1).
Regarding claim 16, Coon et al. teach wherein the system is a cryo-EM system (fig. 1, see paragraph [0044]) and the substrate is part of the cryo-EM probe ([0044]).
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 13, 17-18 and 10-12 (note claims 10-12 directly or indirectly depend on claim 17) are rejected under 35 U.S.C. 103 as being unpatentable over Coon (second interpretation) in view of Konijnenberg et al.
Regarding claim 13, Coon teaches a sample preparation system (fig. 1) comprising:
a) a vacuum chamber or gas chamber (1);
b) a substrate (probe 2 holds sample plate [0045]) positioned with the vacuum chamber or gas chamber (2 is within 1), wherein said substrate comprises a receiving surface (surface that the analyte beam 13 is directed towards of sample plate [0045]);
c) a temperature control means ([0024] teaches temperature control means) able to provide a temperature of 0°C or less to the receiving surface of the substrate ([0044] teaches the temperature is maintained using a coolant, thus controlling the temperature. Paragraph [0011] and [0055] teaches amorphous ice is formed at a temperature of -175 degrees C ([0055]) and that the temperature at the surface of the substrate is -175 ([0011])); and
d) an analyte source (6 see second figure) in fluid communication with the vacuum chamber or gas chamber (as seen in figures 1-2), wherein the analyte source is able to produce a controllable analyte beam comprising charged or uncharged analyte particles (analytes provided by 6), and direct said analyte beam to contact the receiving surface of the substrate (as seen in figure 1).
In this interpretation because analyte source 6 does not provide a solvent, Coon is interpreted to fail to disclose wherein the analyte source is able to produce a analyte beam comprising charged particles and molecules of a solvent.
However, Konijnenberg teaches 20 produces an analyte beam with solvent ([0037]-[0039]), which is controllable via the mass spectrometer including a filter 70 see paragraph [0107]).
Konijnenberg modifies Coon et al. by suggesting creating a solution of analyte and solvent before ionization instead of supplying a separate molecular beam.
Since both inventions are directed electrospray ionization deposition of analyte ions onto a cryo-EM substrate, it would have been obvious to one before the effective filing date of the claimed invention to substitute the separate molecular and analyte beams as suggested by Coon for a solution comprising both solvent and molecules (i.e. analytes) to be supplied to an electrospray ionization source as suggested by Konijnenberg because it would allow for the frozen solvent to protect the gas phase ions during imaging, while not significantly reducing the signal to noise ratio during imaging ([0039]). That is, it would reduce the thickness of ice so as to reduce S/N ratio during imaging while maintaining protection of the ions during imaging.
Regarding claim 17, Coon teaches a modified mass spectrometer device able to provide ions to the analyte source (Coon teaches a modified MS to provide ions to the analyte source ([0022]).
Coon fails to disclose a solution of ions and solvent.
However, Konijnenberg teaches a solution of both solvent and ions ([0037] from ESI 20, wherein MS outputs solvated ions, thus output of MS is interpreted to be the analyte source).
Konijnenberg modifies Coon by suggesting the use of a solution of both a solvent and molecules.
Konijnenberg modifies Coon et al. by suggesting creating a solution of analyte and solvent before ionization instead of supplying a separate molecular beam.
Since both inventions are directed electrospray ionization deposition of analyte ions onto a cryo-EM substrate, it would have been obvious to one before the effective filing date of the claimed invention to substitute the separate molecular and analyte beams as suggested by Coon for a solution comprising both solvent and molecules (i.e. analytes) to be supplied to an electrospray ionization source as suggested by Konijnenberg because it would allow for the frozen solvent to protect the gas phase ions during imaging, while not significantly reducing the signal to noise ratio during imaging ([0039]). That is, it would reduce the thickness of ice so as to reduce S/N ratio during imaging while maintaining protection of the ions during imaging.
Regarding claim 18, Coon teaches wherein the modified mass spectrometer device is able to isolate particles in a mixture ([0013] teaches mass spectrometer isolates or purifies the analyte ions, thus suggesting a mixture of particles that are isolated), wherein the isolate particles have a mass-to-charge- ratio within 2 m/z to preselected 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 specification), the modified ms of Coon is inherently capable of 2 m/z isolation), and wherein the modified mass spectrometer device is able to perform mass spectrometry analysis on the isolated particles (inherent to MS).
Regarding claim 10, Coon teaches wherein the analyte beam is generated using a mass spectrometer device ([0013] teaches mass spectrometer isolates or purifies the analyte ions, thus is generated by isolation), wherein generating an analyte beam comprises performing mass spectrometry analysis on a mixture of particles ([0013] teaches mass spectrometer isolates or purifies the analyte ions, thus suggesting a mixture of particles that are isolated)
Coon fails to disclose identifying desired analyte particles within the mixture
However Konijnenberg et al. teaches identifying desired analyte particles within the mixture ([0263] teaches the mass spectrum indicates that less than 100 water molecules remained attached to the protein ion [0280] teaches a mass spectrum of holoferritin, therefore identification is performed to determine water molecules and holoferrtin), and isolating the desired analyte particles from the mixture based on the mass, size, mass-to-charge ratio, or combinations thereof, of the desired analyte particles ([0110] teaches a mass filter 70 that extracts only those ions within a desired mass section window).
Konijnenberg et al. modifies Coon by suggesting detection and identification of analyte particles and isolating the desired analyte particles.
Since both inventions are directed electrospray ionization deposition of analyte ions onto a cryo-EM substrate, it would have been obvious to one before the effective filing date of the claimed invention to include the detection of a mass spectrum, identify desired analytes and mass filtering based on desired ions because it would provide additional physicochemical properties of the analyte beam under study, while ensuring that the mass filtered windowing is appropriate for deposition.
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).
Regarding claim 12, Coon in view of Konijnenberg teaches enriching, reducing, or altering the solvent in the analyte solution to generate the analyte beam ([0037]-[0038] teaches hydration of the gas phase ions such that the ions have a solvation shell thus altering the solvent from the solution with the molecules to a shell around each of the ions when ionized).
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.
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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.