Prosecution Insights
Last updated: October 01, 2026
Application No. 18/694,831

MATRICES AND SYSTEMS FOR PRESERVATION OF BIOMOLECULES IN VACUUM

Non-Final OA §102§103§112
Filed
Mar 22, 2024
Priority
Sep 23, 2021 — provisional 63/247,705 +3 more
Examiner
MCGUIRK, JOHN SCHUYLER
Art Unit
Tech Center
Assignee
Wisconsin Alumni Research Foundation
OA Round
1 (Non-Final)
78%
Grant Probability
Favorable
1-2
OA Rounds
8m
Est. Remaining
99%
With Interview

Examiner Intelligence

Grants 78% — above average
78%
Career Allowance Rate
177 granted / 227 resolved
+18.0% vs TC avg
Strong +48% interview lift
Without
With
+48.4%
Interview Lift
resolved cases with interview
Typical timeline
3y 2m
Avg Prosecution
36 currently pending
Career history
257
Total Applications
across all art units

Statute-Specific Performance

§101
6.0%
-34.0% vs TC avg
§103
42.0%
+2.0% vs TC avg
§102
16.1%
-23.9% vs TC avg
§112
32.8%
-7.2% vs TC avg
Black line = Tech Center average estimate • Based on career data from 227 resolved cases

Office Action

§102 §103 §112
Notice of Pre-AIA or AIA Status The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . Claim Status Claims 41-60 are pending and examined. Claims 1-40 are canceled. Claim Objections Claim 48-49 and 56-57 are objected to because of the following informalities: Regarding claim 48, Lns. 1-2 recite, “wherein the step of depositing the target molecules is performed a temperature…”, which is grammatically incorrect. The above limitation needs to be amended to recite, “wherein the step of depositing the target molecules is performed at a temperature…” to be grammatically correct. Regarding claim 49, the claim recites, “wherein the liquid or semiliquid substance comprise glycerol…proline, trehalose, and combinations thereof”. However, “comprise” is grammatically incorrect, and should be amended to recite “comprises” to be grammatically correct. Further, as currently constructed, the phrase “and combinations thereof” in this limitation implies that all of the listed substances need to be present in combination in order to satisfy the claim, which is likely not Applicant’s intention. Therefore, the above limitation needs to be amended to recite, “wherein the liquid or semiliquid substance comprises glycerol…proline, or trehalose, and combinations thereof” to be grammatically correct, and recite that one or more of the listed substances needs to be present in order to satisfy the claim. Regarding claim 56, step e) recites, “where the controller controls the first ion focusing optics and ion separation optics so as to…v) contacting the substrate…”. However, in this limitation, “contacting” needs to be amended to recite, “contact” to be grammatically correct. Regarding claim 57, Lns. 2-3 recite, “wherein the controller is able to controller the mass analyzer”, which is grammatically incorrect. The above limitation needs to be amended to recite, “wherein the controller is able to control the mass analyzer” to be grammatically correct. Appropriate correction is required. 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 54 and 58 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. Regarding claim 54, Ln. 2 recites, “a modified mass spectrometer”. However, it is unclear how the mass spectrometer is modified, and what it is modified in relation to. Is it modified in comparison to a previously unmodified mass spectrometer? If so, how? Further clarification is needed. Claim 58 recites the limitation "the mass analyzer" in Ln. 2. There is insufficient antecedent basis for this limitation in the claim. Further, it is unclear from this limitation if the mass analyzer is positively recited as part of the system or not. For purposes of compact prosecution, the above limitation has been examined as, “a mass analyzer”, and the mass analyzer has been examined as positively recited as part of the system. Claim Rejections - 35 USC § 102 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. The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action: A person shall be entitled to a patent unless – (a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention. (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 41-43, 45-50, and 52-60 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Benesch et al., “Separating and visualizing protein assemblies by means of preparative mass spectrometry and microscopy”, 2010, Journal of Structural Biology, Vol. 172, Pgs. 161-168 (hereinafter Benesch). Regarding claim 41, Benesch discloses a method for preparing a sample (Pg. 166 Col. 1 1st Full Para.). The method comprises the steps of: a) contacting a substrate surface with a liquid or semiliquid substance thereby forming a matrix layer of the liquid or semiliquid substance on the substrate surface (Pg. 166 Col. 1 1st Full Para., a liquid layer containing glycerol or sucrose is formed on a perforated carbon-coated grid). and b) depositing target molecules having an initial structure onto or within the matrix layer under vacuum (Pg. 166 Col. 1 1st Full Para., the target is removed from vacuum after landing the particles into the liquid layer, implying that the target molecules are deposited under vacuum). The target molecules are at least partially embedded in the matrix layer (Pg. 166 Col. 1 1st Full Para., the particles are landed into the liquid layer) and wherein the initial structure of at least a portion of the target molecules is maintained while within the vacuum (Pg. 166 Col. 1 1st Full Para., the fact that successful reconstructions of the particles can be obtained implies that at least a portion of the target molecules is maintained, see also Pg. 166 Col. 2 Last Para.). Regarding claim 42, Benesch discloses the method of claim 41 wherein the target molecules are ions and the method comprises generating the target molecules by ionizing precursor molecules (see Fig. 1A at nanoESI source). Regarding claim 43, Benesch discloses the method of claim 41 wherein the target molecules comprise peptides, proteins, or ions thereof (Abstract). Regarding claim 45, Benesch discloses the method of claim 41 further comprising imaging the target molecules deposited onto or within the matrix layer, wherein the imaging comprises transmission electron microscopy (TEM), scanning electron microscopy (SEM), cryogenic electron microscopy (cryo- EM), X-ray imaging, fluorescent labeling, immunolabeling, and combinations thereof (Abstract). Regarding claim 46, Benesch discloses the method of claim 45 further comprising generating three-dimensional reconstructed images of the target molecules (Fig. 4). Regarding claim 47, Benesch discloses the method of claim 41 wherein the step of depositing the target molecules is performed at a pressure equal to or less than 10-4 Torr (Fig. 1 and associated legend, vacuum conditions imply an absence of pressure, meaning that the pressure will intrinsically be below the claimed value). Regarding claim 48, Benesch discloses the method of claim 41 wherein the step of depositing the target molecules is performed a temperature between -90°C and 50°C (Fig. 1 and associated legend, absent any description of the temperature conditions, it is safe to assume the operating temperature of the mass spectrometer will be approximately room temperature i.e. approximately 20 degrees Celsius). Regarding claim 49, Benesch discloses the method of claim 41 wherein the liquid or semiliquid substance comprises glycerol, water, ethylene glycol, poly(ethylene) glycol (PEG), poly(propylene) glycol (PPG), triethanolamine (TEA), TritonX-100, diglycerol, glycose, sucrose, inositol, glycine, proline, or trehalose, and combinations thereof (Pg. 166 Col. 1 at 1st Full Para.). Regarding claim 50, Benesch discloses the method of claim 41 further comprising a staining step comprising contacting exposed areas of the partially embedded target molecules with metal particles or a metal containing solution (Pg. 162 Col. 1 at 2.3). Regarding claim 52, Benesch discloses a method for preparing a sample for electron microscopy (EM) (Pg. 166 Col. 1 1st Full Para.). The method comprises the steps of: a) contacting a substrate surface with a liquid or semiliquid substance thereby forming a matrix layer of the liquid or semiliquid substance on the substrate surface, wherein the substrate is an electron microscopy (EM) grid (Pg. 166 Col. 1 1st Full Para., a liquid layer containing glycerol or sucrose is formed on a perforated carbon-coated grid). b) generating a first distribution of precursor ions from a sample of target molecules (Pg. 166 Col. 1 1st Full Para., Pgs. 162-164 at Sections 3.1, 3.2). c) separating a portion of ions from the first distribution of precursor ions according to mass-to-charge ratios of the precursor ions, thereby generating separated ions molecules (Pg. 166 Col. 1 1st Full Para., Pgs. 162-164 at Sections 3.1, 3.2, particularly at 3.1 describing a mass spectrometer for selective deposition of protein assemblies). d) generating an ion beam containing the separated ions (Pgs. 162-164 at Sections 3.1, 3.2). e) directing the ion beam to the substrate surface under vacuum molecules (Pg. 166 Col. 1 1st Full Para., Pgs. 162-164 at Sections 3.1, 3.2). Thereby depositing target molecule ions onto or within the matrix layer, wherein the target molecule ions are partially embedded in the matrix layer and wherein the structure of at least a portion of the target molecule ions is retained (Pg. 166 Col. 1 1st Full Para., the fact that successful reconstructions of the particles can be obtained implies that at least a portion of the target molecules is maintained, see also Pg. 166 Col. 2 Last Para.). Regarding claim 53, Benesch discloses the method of claim 52 wherein the target molecules comprise ions generated from peptides or proteins (Abstract). Regarding claim 54, Benesch discloses the method of claim 52 wherein the step of generating a first distribution of precursor ions and the separating step are performed by a modified mass spectrometer (Pgs. 162-164 at Sections 3.1, 3.2, particularly at 3.1 A mass spectrometer for selective deposition of protein assemblies). Regarding claim 55, Benesch discloses the method of claim 52 further comprising a staining step comprising contacting exposed areas of the partially embedded target molecules with metal particles or a metal containing solution (Pg. 162 Col. 1 at 2.3). Regarding claim 56, Benesch discloses a system for depositing target molecules on a substrate (see Fig. 1 and associated legend). The system comprises: a) an ion source able to generate ions from a sample of molecules (see Fig. 1A at nanoESI source). b) first ion focusing optics in fluid communication with the ion source (see Fig. 1 and associated legend, which includes deflection plates, see [0047] of the instant Specification, which states that ion deflectors are an example of ion optical device components). c) ion separation optics in fluid communication with the first ion focusing optics, wherein the first ion focusing optics are able to transport ions from the ion source to the ion separation optics, and wherein the ion separation optics are able to separate ions according to the mass- to-charge ratios of the ions (see Fig. 1 and associated legend, and Pgs. 162-164 at Sections 3.1, 3.2). d) a sample chamber in fluid communication with the ion separation optics, wherein the sample chamber maintains a vacuum and contains a substrate able to be inserted into and removed from the sample chamber while maintaining the vacuum (see Fig. 1A and associated legend). e) a controller, operably connected to the first ion focusing optics, the ion separation optics, and the sample chamber (the mass spectrometer implicitly includes a controller). The controller controls the first ion focusing optics and ion separation optics so as to: i) transport the ions from the ion source to the ion separation optics (see Fig. 1 and associated legend, and Pgs. 162-164 at Sections 3.1, 3.2). ii) generate a first distribution of precursor ions from the transported ions (see Pgs. 162-164 at Sections 3.1, 3.2, particularly at paragraph bridging pages 162 and 163). iii) isolate a target range of mass-to-charge ratios within the first distribution of precursor ions, thereby generating separated ions (see Pgs. 162-164 at Sections 3.1, 3.2, particularly at paragraph bridging pages 162 and 163). iv) generate an ion beam comprising the separated ions (see Fig. 1 and associated legend). v) contact the substrate in the sample chamber with the ion beam, thereby depositing separated ions on the substrate under a vacuum (see Fig. 1 and associated legend). Note: The instant Claims contain a large amount of functional language (ex: “able to generate ions…”, “able to transport ions…”, “able to separate ions…”, etc.). However, functional language does not add any further structure to an apparatus beyond a capability. Apparatus claims must distinguish over the prior art in terms of structure rather than function (see MPEP 2114). Therefore, if the prior art structure is capable of performing the function, then the prior art meets the limitation in the claims. Regarding claim 57, Benesch discloses the system of claim 56 further comprising a mass analyzer in fluid communication with the ion separation optics able to detect the separated ions, wherein the controller is able to control the mass analyzer so as to measure the mass-to-charge ratios of the separated ions and generate mass spectrometry data (see Fig. 1 and associated legend, which describes a line-of-sight detector for ion beam imaging and diagnostics, see also paragraph bridging Pgs. 162-163). Regarding claim 58, Benesch discloses the system of claim 56 further comprising second ion focusing optics in fluid communication with the ion separation optics, the mass analyzer, and sample chamber, wherein the second ion focusing optics are under operational control of the controller so as to be able to transport the separated ions from the ion separation optics to the mass analyzer and/or the sample chamber (see Fig. 1 and associated legend, which describes multiple deflection plates). Regarding claim 59, Benesch discloses the system of claim 56 wherein the substrate comprises a matrix layer of a liquid or semiliquid substance deposited on a surface of the substrate (Pg. 166 Col. 1 1st Full Para.). Regarding claim 60, Benesch discloses the system of claim 56 wherein the sample chamber has an interior pressure equal to or less than 10-4 Torr and the sample chamber has an interior temperature between -90°C and 50°C (Fig. 1 and associated legend, vacuum conditions imply an absence of pressure, meaning that the pressure will intrinsically be below the claimed value. Further, absent any description of the temperature conditions, it is safe to assume the operating temperature of the mass spectrometer will be approximately room temperature i.e. approximately 20 degrees Celsius). Claims 41-42, 45, 47-50, and 56-60 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Siuzdak et al., “Mass spectrometry and viral analysis”, January 1996, Chemistry & Biology, Vol. 3, Pgs. 45-48 (hereinafter Siuzdak). Regarding claim 41, Siuzdak discloses a method for preparing a sample (Fig. 1). The method comprises the steps of: a) contacting a substrate surface with a liquid or semiliquid substance thereby forming a matrix layer of the liquid or semiliquid substance on the substrate surface (Pg. 47, Col. 2 at Materials and Methods-Electrospray MS, the collector was coated with a thin layer of methanol/glycerol). b) depositing target molecules having an initial structure onto or within the matrix layer under vacuum (Pg. 47, Col. 2 at Materials and Methods-Electrospray MS, the collector was placed directly behind the orifice within the vacuum of the mass spectrometer, see also Fig. 1). The target molecules are at least partially embedded in the matrix layer and wherein the initial structure of at least a portion of the target molecules is maintained while within the vacuum (Pg. 47, Col. 1, 2nd Para., the virus retained infectivity even with the potential for damage caused by ionization, vacuum conditions, glycerol, electromagnetic fields, and impact with the collector. This implies that the target molecules, i.e. the virus, retained some of their initial structure). Regarding claim 42, Siuzdak discloses the method of claim 41 wherein the target molecules are ions and the method comprises generating the target molecules by ionizing precursor molecules (Pg. 47 Col. 2 at Materials and Methods-Electrospray MS). Regarding claim 45, Siuzdak discloses the method of claim 41 further comprising imaging the target molecules deposited onto or within the matrix layer, wherein the imaging comprises transmission electron microscopy (TEM), scanning electron microscopy (SEM), cryogenic electron microscopy (cryo- EM), X-ray imaging, fluorescent labeling, immunolabeling, and combinations thereof (Pg. 47 Col. 2 at Materials and methods-Electron microscopy). Regarding claim 47, Siuzdak discloses the method of claim 41 wherein the step of depositing the target molecules is performed at a pressure equal to or less than 10-4 Torr (Pg. 47, Col. 2 at Materials and Methods-Electrospray MS, vacuum conditions imply an absence of pressure, meaning that the pressure will intrinsically be below the claimed value). Regarding claim 48, Siuzdak discloses the method of claim 41 wherein the step of depositing the target molecules is performed a temperature between -90°C and 50°C (Pg. 47, Col. 2 at Materials and Methods-Electrospray MS, absent any description of the temperature conditions, it is safe to assume the operating temperature of the mass spectrometer will be approximately room temperature i.e. approximately 20 degrees Celsius). Regarding claim 49, Siuzdak discloses the method of claim 41 wherein the liquid or semiliquid substance comprises glycerol, water, ethylene glycol, poly(ethylene) glycol (PEG), poly(propylene) glycol (PPG), triethanolamine (TEA), TritonX-100, diglycerol, glycose, sucrose, inositol, glycine, proline, or trehalose, and combinations thereof (Pg. 47, Col. 2 at Materials and Methods-Electrospray MS). Regarding claim 50, Siuzdak discloses the method of claim 41 further comprising a staining step comprising contacting exposed areas of the partially embedded target molecules with metal particles or a metal containing solution (Pg. 47 Col. 2 at Materials and Methods-Electron microscopy). Regarding claim 56, Siuzdak discloses a system for depositing target molecules on a substrate (Fig. 1). The system comprises: a) an ion source able to generate ions from a sample of molecules (Fig. 1). b) first ion focusing optics in fluid communication with the ion source (Fig. 1, which shows that the path of ions is deflected, see [0047] of the instant Specification, which states that ion deflectors are an example of ion optical device components. Further, the description of Fig. 1 states that the quadrupoles Q0-Q3 allow for ion focusing). c) ion separation optics in fluid communication with the first ion focusing optics, wherein the first ion focusing optics are able to transport ions from the ion source to the ion separation optics, and wherein the ion separation optics are able to separate ions according to the mass- to-charge ratios of the ions (Fig. 1, the description of Fig. 1 states that the quadrupoles Q0-Q3 allow for mass selection). d) a sample chamber in fluid communication with the ion separation optics, wherein the sample chamber maintains a vacuum and contains a substrate able to be inserted into and removed from the sample chamber while maintaining the vacuum (Pg. 47 Col. 2 at Materials and methods-Electrospray MS). e) a controller, operably connected to the first ion focusing optics, the ion separation optics, and the sample chamber (the mass spectrometer implicitly discloses a controller connected to the individual parts thereof). The controller controls the first ion focusing optics and ion separation optics so as to: i) transport the ions from the ion source to the ion separation optics (Pg. 47 Col. 2 at Materials and methods-Electrospray MS, see also Fig. 1). ii) generate a first distribution of precursor ions from the transported ions (Pg. 47 Col. 2 at Materials and methods-Electrospray MS, Pg. 47 Cols. 1-2 at Significance, which states that biomolecules and biomolecular complexes can be differentiated when they vary in mass by 5% or more, allowing a subgroup within a population to be measured, see also Fig. 1). iii) isolate a target range of mass-to-charge ratios within the first distribution of precursor ions, thereby generating separated ions (Pg. 47 Col. 2 at Materials and methods-Electrospray MS, Pg. 47 Cols. 1-2 at Significance, which states that biomolecules and biomolecular complexes can be differentiated when they vary in mass by 5% or more, allowing a subgroup within a population to be measured, see also Fig. 1, see also Pg. 45 at Abstract, describing ion filtering through a mass analyzer). iv) generate an ion beam comprising the separated ions (Pg. 47 Cols. 1-2 at Significance, which states that biomolecules and biomolecular complexes can be differentiated when they vary in mass by 5% or more, allowing a subgroup within a population to be measured). v) contact the substrate in the sample chamber with the ion beam, thereby depositing separated ions on the substrate under a vacuum (Fig. 1, Pg. 47 Col. 2 at Materials and methods-Electrospray MS). Regarding claim 57, Siuzdak discloses the system of claim 56 further comprising a mass analyzer in fluid communication with the ion separation optics able to detect the separated ions, wherein the controller is able to control the mass analyzer so as to measure the mass-to-charge ratios of the separated ions and generate mass spectrometry data (Pg. 45 at Abstract, where the ions have been filtered through the mass analyzer, and then analyzed by transmission electron microscopy. See also Fig. 1 which shows Q0-Q3, which allow for ion focusing and mass selection). Regarding claim 58, Siuzdak discloses the system of claim 56 further comprising second ion focusing optics in fluid communication with the ion separation optics, the mass analyzer, and sample chamber, wherein the second ion focusing optics are under operational control of the controller so as to be able to transport the separated ions from the ion separation optics to the mass analyzer and/or the sample chamber (Fig. 1 at four quadrupoles Q0-Q3). Regarding claim 59, Siuzdak discloses the system of claim 56 wherein the substrate comprises a matrix layer of a liquid or semiliquid substance deposited on a surface of the substrate (Pg. 47 Col. 2 at Materials and methods-Electrospray MS). Regarding claim 60, Siuzdak discloses the system of claim 56 wherein the sample chamber has an interior pressure equal to or less than 10-4 Torr and the sample chamber has an interior temperature between -90°C and 50°C (Pg. 47, Col. 2 at Materials and Methods-Electrospray MS, vacuum conditions imply an absence of pressure, meaning that the pressure will intrinsically be below the claimed value. Further, absent any description of the temperature conditions, it is safe to assume the operating temperature of the mass spectrometer will be approximately room temperature i.e. approximately 20 degrees Celsius). 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. 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. The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows: 1. Determining the scope and contents of the prior art. 2. Ascertaining the differences between the prior art and the claims at issue. 3. Resolving the level of ordinary skill in the pertinent art. 4. Considering objective evidence present in the application indicating obviousness or nonobviousness. 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. Claim 44 is rejected under 35 U.S.C. 103 as being unpatentable over Benesch. Regarding claim 44, Benesch discloses the method of claim 43. Benesch further discloses that the peptides, proteins, or ions thereof have gross topological features that are retained while within the vacuum (Benesch Abstract). Benesch further discloses that the quaternary structure is retained (see Pg. 165 at 4.1 Preservation of quaternary structure in the gas phase). Benesch fails to explicitly disclose that the secondary or tertiary structure is retained. However, it would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to have the secondary or tertiary structure be retained, in order to ensure that the biomolecules that are being deposited remain as close to their original structure as possible, thereby ensuring that subsequent measurements on the biomolecules are accurate. Claim 51 is rejected under 35 U.S.C. 103 as being unpatentable over Benesch, as applied to claims 41-43, 45-50, and 52-60 above, in view of Chen et al. (US Pub. No. 2016/0116384; hereinafter Chen). Regarding claim 51, Benesch discloses the method of claim 41. Benesch fails to explicitly disclose binding a portion of the partially embedded target molecules to a fluorescent tag, epitope tag or antibody tag. Chen is in the analogous field of sample preparation and analysis (Chen [0007]). Chen teaches binding target molecules to a fluorescent tag (Chen [0027]). It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the method of Benesch with the teachings of Chen to bind a portion of the partially embedded target molecules to a fluorescent tag, in order to assist in microscopic analysis (Chen [0027]). Claim 51 is rejected under 35 U.S.C. 103 as being unpatentable over Siuzdak, as applied to claims 41-42, 45, 47-50, and 56-60 above, in view of Chen. Regarding claim 51, Siuzdak discloses the method of claim 41. Siuzdak fails to explicitly disclose binding a portion of the partially embedded target molecules to a fluorescent tag, epitope tag or antibody tag. Chen is in the analogous field of sample preparation and analysis (Chen [0007]). Chen teaches binding target molecules to a fluorescent tag (Chen [0027]). It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the method of Siuzdak with the teachings of Chen to bind a portion of the partially embedded target molecules to a fluorescent tag, in order to assist in microscopic analysis (Chen [0027]). Conclusion Any inquiry concerning this communication or earlier communications from the examiner should be directed to John McGuirk whose telephone number is (571)272-1949. The examiner can normally be reached M-F 8am-530pm. 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, Charles Capozzi can be reached at (571) 270-3638. 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. /JOHN MCGUIRK/Primary Examiner, Art Unit 1798
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Prosecution Timeline

Mar 22, 2024
Application Filed
Sep 15, 2026
Non-Final Rejection mailed — §102, §103, §112 (current)

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Prosecution Projections

1-2
Expected OA Rounds
78%
Grant Probability
99%
With Interview (+48.4%)
3y 2m (~8m remaining)
Median Time to Grant
Low
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