Prosecution Insights
Last updated: August 18, 2026
Application No. 18/261,267

FREEZING AND JACKETING GAS-PHASE BIOMOLECULES WITH AMORPHOUS ICE FOR ELECTRON MICROSCOPY

Final Rejection §103
Filed
Jul 13, 2023
Priority
Jan 13, 2021 — provisional 63/136,850 +1 more
Examiner
BOWERS, NATHAN ANDREW
Art Unit
1799
Tech Center
1700 — Chemical & Materials Engineering
Assignee
Wisconsin Alumni Research Foundation
OA Round
2 (Final)
59%
Grant Probability
Moderate
3-4
OA Rounds
5m
Est. Remaining
91%
With Interview

Examiner Intelligence

Grants 59% of resolved cases
59%
Career Allowance Rate
811 granted / 1369 resolved
-5.8% vs TC avg
Strong +32% interview lift
Without
With
+32.1%
Interview Lift
resolved cases with interview
Typical timeline
3y 6m
Avg Prosecution
56 currently pending
Career history
1424
Total Applications
across all art units

Statute-Specific Performance

§101
0.5%
-39.5% vs TC avg
§103
53.9%
+13.9% vs TC avg
§102
13.5%
-26.5% vs TC avg
§112
18.3%
-21.7% vs TC avg
Black line = Tech Center average estimate • Based on career data from 1369 resolved cases

Office Action

§103
DETAILED ACTION 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. 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. Claims 53-58 are rejected under 35 U.S.C. 103 as being unpatentable over Coon (WO 2019010436) in view of Boyarkin “Cryogenically cooled octupole ion trap for spectroscopy of biomolecular ions”. With respect to claim 53, Coon discloses a method for preparing a sample for cryo-electron microscopy comprising the steps of generating charged or uncharged analyte particles and contacting a substrate surface with the analyte particles at a temperature of -90°C or less to form a layer of analyte particles on the substrate surface (“forming an analyte beam containing charged or uncharged analyte particles to be analyzed using EM”). Coon forms a vapor stream of atoms or molecules and contacts the substrate with the vapor stream under a vacuum at a temperature of -90°C or less to form an amorphous solid layer on the substrate surface (“a method for preparing a sample for cryo-electron microscopy (cryo-EM) comprising the steps of forming a vapor stream of atoms or molecules, and directing the vapor stream toward a substrate surface such that the atoms or molecules impinge on the substrate surface while under vacuum. The substrate surface is at a temperature of −100°C or less”). Analyte particles are embedded on or within the amorphous solid layer (“The deposited analyte particles may be embedded within the amorphous solid layer, deposited on the surface, or both”). The amorphous solid layer has a thickness of 2 microns or less (“the vapor stream is controlled, or the deposited amorphous solid layer is milled, etched, or otherwise refined, so that the amorphous solid layer has a thickness of 2 microns or less, 150 nm or less, or 100 nm or less”). This is taught in paragraphs [0011]-[0021]. Coon states that charged or uncharged ion particles may be proteins and may be generated and purified during mass spectrometry (see paragraph [0009]), but does not specifically state that the charged or uncharged ion particles are cooled to a temperature of -90°C or less prior to contacting the vapor stream. Boyarkin discloses a method of preparing charged or uncharged analyte particles for measurement using mass spectrometry. Boyarkin teaches that polypeptides, for example, are prepared in a cold ion trap cooled to under -90°C. Helium buffer gas is used to significantly reduce the temperature of the analyte particles in preparation for mass spectrometry, as it is well known that cooling plays a critical role in mass spectrometry by stabilizing ion beams, reducing kinetic energy spread, and maintaining precise instrument performance for accurate results. The Boyarkin system and method is especially suitable for heavy biological ions. Before the effective filing date of the claimed invention, it would have been obvious to ensure that the analyte particles produced by Coon are cooled to -90°C or less prior to contacting the vapor stream. Boyarkin indicates that it is well known in the art that precise spectroscopy is enabled through the creation of cold molecules (“Cooling biomolecular ions to sufficiently low, cryogenic temperatures may, eventually, collapse all of them into the vibrational ground state, fully suppressing vibrational spectral congestion”). These teachings of Boyarkin would have been particularly relevant to Coon since Coon is interested in further evaluating analyte particles generated and evaluated during mass spectrometry. With respect to claims 54 and 55, Coon and Boyarkin disclose the combination as described above. Coon further teaches in paragraph [0017] that the surface is contacted with analyte particles and the vapor stream concurrently. Alternatively, the substrate surface may be contacted with analyte particles prior to being contacted with the vapor stream. With respect to claim 56, Coon and Boyarkin disclose the combination as described above. Coon teaches in paragraph [0020] that the vapor stream includes cyclohexanol, methanol, ethanol, isopentane, water, O2, Si, SiO2, S, C, Ge, Fe, Co and/or Bi. With respect to claim 57, Coon and Boyarkin disclose the combination as described above. Coon teaches in paragraphs [0009]-[0015] that the analyte particles are ions generated from a mass spectrometer device using electrospray ionization or laser desorption. With respect to claim 58, Coon and Boyarkin disclose the combination as described above. As previously discussed, Boyarkin teaches a cold ion trap, which reads on the claimed cooling chamber. Coon teaches that the cooled particles are transported into a vacuum chamber containing the substrate surface. See, for example, paragraph [0011] (“directing the vapor stream toward a substrate surface such that the atoms or molecules impinge on the substrate surface while under vacuum”). Response to Arguments In response to Applicant’s amendment filed 04 June 2026, the previous rejections have been withdrawn. However, upon further consideration, a new ground of rejection is made in view of the combination of Coon with Boyarkin. Conclusion Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a). A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action. Any inquiry concerning this communication or earlier communications from the examiner should be directed to NATHAN ANDREW BOWERS whose telephone number is (571)272-8613. The examiner can normally be reached M-F 7am-5pm. 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, Michael Marcheschi can be reached at (571) 272-1374. 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. /NATHAN A BOWERS/Primary Examiner, Art Unit 1799
Read full office action

Prosecution Timeline

Jul 13, 2023
Application Filed
Jan 15, 2026
Non-Final Rejection mailed — §103
Jun 04, 2026
Response Filed
Jun 11, 2026
Final Rejection mailed — §103 (current)

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Study what changed to get past this examiner. Based on 5 most recent grants.

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Prosecution Projections

3-4
Expected OA Rounds
59%
Grant Probability
91%
With Interview (+32.1%)
3y 6m (~5m remaining)
Median Time to Grant
Moderate
PTA Risk
Based on 1369 resolved cases by this examiner. Grant probability derived from career allowance rate.

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