DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election without traverse of Group III, claims 53-57 in the reply filed on 17 November 2025 is acknowledged.
Claims 38-52 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 17 November 2025.
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 53-57 are rejected under 35 U.S.C. 103 as being unpatentable over Coon (WO 2019010436) in view of Wall “Preparation of cold molecules for high-precision measurements”.
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]. Although Coon states that the substrate is maintained at a temperature of -90°C or less, Coon does not expressly state that the analyte particles are also cooled to a temperature of -90°C or less prior to contacting the substrate.
Wall discloses a method of preparing charged or uncharged analyte particles for measurement. In one example, Wall teaches that pulsed supersonic beam and/or laser cooling and/or buffer gas cooling apparatuses are coupled with a Stark decelerator to prepare slow and ultracold analyte particles for high-precision spectroscopy. Wall states that analyte particles are cooled to a temperature as low as 1.4 K.
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 substrate surface. Wall indicates that it is well known in the art that precise spectroscopy is enabled through the creation of cold molecules (“it is often advantageous for the molecules to be cold and slow, offering a high level of state selectivity and affording long interaction times with low divergence beams”). Wall describes on page 2 that a variety of direct and indirect strategies are available and may be used to create ultracold analyte particles. These teachings of Wall would have been particularly relevant to Coon since Coon is interested in further evaluating analyte particles generated from a mass spectrometer.
With respect to claims 54 and 55, Coon and Wall 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 Wall 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 Wall 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.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. The McQueen (US 20200363301), Wang (US 20160351374), Braun (US 20190250078), Godfrin (US 11703429) and Closs (US 20220291098) references teach the state of the art regarding cryo-Em.
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.
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/NATHAN A BOWERS/Primary Examiner, Art Unit 1799