Prosecution Insights
Last updated: October 04, 2026
Application No. 18/335,770

PHOTOSTABLE CRYSTALLINE SUBSTRATES FOR FLUORESCENCE MICROSCOPY

Final Rejection §103
Filed
Jun 15, 2023
Examiner
LEE, SHUN K
Art Unit
2884
Tech Center
2800 — Semiconductors & Electrical Systems
Assignee
Araceli Biosciences Inc.
OA Round
4 (Final)
42%
Grant Probability
Moderate
5-6
OA Rounds
2m
Est. Remaining
58%
With Interview

Examiner Intelligence

Grants 42% of resolved cases
42%
Career Allowance Rate
303 granted / 718 resolved
-25.8% vs TC avg
Strong +16% interview lift
Without
With
+16.3%
Interview Lift
resolved cases with interview
Typical timeline
3y 6m
Avg Prosecution
37 currently pending
Career history
767
Total Applications
across all art units

Statute-Specific Performance

§101
2.2%
-37.8% vs TC avg
§103
54.6%
+14.6% vs TC avg
§102
14.7%
-25.3% vs TC avg
§112
25.6%
-14.4% vs TC avg
Black line = Tech Center average estimate • Based on career data from 718 resolved cases

Office Action

§103
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 . Claim Interpretation MPEP § 2111.01 states that “… Under a broadest reasonable interpretation (BRI), words of the claim must be given their plain meaning, unless such meaning is inconsistent with the specification. The plain meaning of a term means the ordinary and customary meaning given to the term by those of ordinary skill in the art at the relevant time. The ordinary and customary meaning of a term may be evidenced by a variety of sources, including the words of the claims themselves, the specification, drawings, and prior art. However, the best source for determining the meaning of a claim term is the specification - the greatest clarity is obtained when the specification serves as a glossary for the claim terms …”. Thus under a broadest reasonable interpretation, the greatest clarity is obtained when the specification (e.g., see “… single microscope system and/or plurality of microscope systems may be matched (e.g., balanced) … balancing refers to adjusting operational settings of a fluorescence microscope, such as emission source intensity, in order to achieve reproducible fluorescence assays on a single microscope system over time and/or between a plurality of microscope systems …” in paragraphs 2 and 17) serves as a glossary for the claim term “balancing”. The specification (e.g., see “… fiducial marker 550 may be shaped as a cross, however, other shapes have been considered. Fiducial marker 550 may be etched or otherwise permanently formed in or on inorganic crystalline fluorophore 510 …” in paragraph 48) serves as a glossary for the claim term “fiducial marker”. 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 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 of this title, 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. Claim(s) 1-8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Earney et al. (US 2021/0055224) in view of Haberstroh et al. (US 2011/0076687), Engelhardt (US 2012/0322267), and Boese (US 2014/0134711). In regard to claim 1, Earney et al. disclose a photostable fluorescence balancing target, comprising: (a) a holder (e.g., “… body 102 … central pocket 114 is configured to receive the optical target 120. The optical target 120 may be secured within the pocket 114 in various manners, such as with an adhesive … channels 116 receive an adhesive that bonds to the glass layer and the body 102, thereby covering and hermetically sealing the optical target 120 from the external environment … adhesive may be silicone which is highly stable in alcohol, whereas UV cure adhesive tend to break down in alcohol. The silicone is injected until the channels 116 arc filled …” in paragraphs 59 and 66); (b) an inorganic crystalline fluorophore affixed to the holder, wherein the inorganic crystalline fluorophore affixed to the holder via a silicone adhesive (e.g., “… optical target 120 represents a solid body structure that includes a solid host material and a fluorescing material embedded within the solid host material … solid host material may include at least one of … crystalline materials … fluorescing material may be a rare-earth element such as rare earth ions: Tm3+ (455 nm), Ho3+ (550 nm), Tb3+ (540 nm), Eu3+ (611 nm), Sm3+ (550 nm), Pr3+ (488, 590 nm), Dy3+ (480 nm & 575 nm), or Er3+ (550 nm & 660 nm); an element from the Actinide series: U; transition metal ions: Ti3+, Cr2+/3+ etc. … fluorescing material emits in one or more emission channels of interest …” in paragraphs 52-54); and (c) a fiducial marker positioned on the inorganic crystalline fluorophore (e.g., “… may be combined … grating layer 122 may have different regions to be used in connection with different types of alignment operations and/or calibration tests. For example, as discussed below in connection with FIG. 2D, grating layer 122 may include one or more … fiducials … grating structure may be patterned directly on the solid fluorescing substrate (e.g., see FIG. 2E) to form a monolithic structure …” in paragraphs 25 and 75), wherein the fiducial marker is patterned directly on the inorganic crystalline fluorophore (e.g., “… instrument moves the objective to the auto centering fiducial and performs an XY stage position repeatability test. The instrument moves the X and Y stage multiple times from each direction to the auto centering fiducial and after each move it takes an image of the auto centering fiducial. Ideally, the auto centering fiducial would show up at exactly the same position in the image after every move … inspection apparatus can control the measured fluorescence to a desired tolerance (e.g., +/-0.6% in red and +/-0.1% in green). Measuring intensity of the inspection apparatus at a certain scan speed and laser power on one instrument will provide measurement information indicative of an intensity to expect on substantially all similar instruments. The fluorescent intensity measurement from the inspection apparatus can be utilized to indicate whether the instrument is behaving properly (e.g., providing proper laser power delivered to the flow cell, proper amount of fluorescent light collected and delivered to the camera, etc.). Given that the emission characteristics of the inspection apparatus will not change over time, any change in measured fluorescent intensity over the life of the instrument will indicate that either the proper laser power is not being delivered to the flow cell or not all the fluorescent light is being delivered to the camera …” in paragraphs 159 and 161). The target of Earney et al. lacks an explicit description of details of the “… solid host material …” such as the inorganic crystalline fluorophore comprising a natural or synthetic gemstone, an explicit description of details of the “… patterned directly on the solid fluorescing substrate …” such as etched, and an explicit description of details of the “… adhesive may be silicone …” such as non-fluorescent transparent properties. However, “… solid host material …” details are known to one of ordinary skill in the art (e.g., see “… commercially available: diamond, silicon carbide (moissanite), ruby, sapphire, zircon, beryl, emerald, opal, quartz, jade, topaz, turquoise, lapis lazuli, chrysoberyl, amber, spine!, tourmaline, tanzanite, zincblende, wurtzite, and others …” in paragraph 36 of Haberstroh et al., “… patterned directly …” details are known to one of ordinary skill in the art (e.g., see “… methods for patterning wide band gap material substrates such as silicon carbide (SiC) substrates, aluminum oxide (Al2O3) substrates (e.g. sapphire substrates or ruby substrates), diamond substrates, wide band gap III-V semiconductor substrates, wide band gap II-VI semiconductor substrates, etc., by means of plasma etching may be provided. Patterning the substrate may, for example, include forming structures such as e.g. trenches, grooves, holes, vias, etc. in the substrate …” in paragraph 176 of Engelhardt), and “… adhesive …” details are known to one of ordinary skill in the art (e.g., see “… a non-fluorescent, transparent adhesive, preferably a silicone adhesive, particularly Sylguard 184 …” in paragraph 77 of Boese). It should be noted that “when a patent claims a structure already known in the prior art that is altered by the mere substitution of one element for another known in the field, the combination must do more than yield a predictable results”. KSR International Co. v. Teleflex Inc., 550 U.S. 398 at 416, 82 USPQ2d 1385 (2007) at 1395 (citing United States v. Adams, 383 U.S. 39, 40 [148 USPQ 479] (1966)). See MPEP § 2143. In this case, one of ordinary skill in the art could have substituted a known conventional solid host material (e.g., comprising details such as “commercially available” “ruby”) for the unspecified solid host material of Earney et al., substituted a known conventional commercially available silicone adhesive (e.g., comprising details such as a “Sylguard 184” having “non-fluorescent, transparent adhesive” properties) for the unspecified silicone adhesive of Earney et al., and substituted a known conventional patterning technique (e.g., comprising details such as “plasma etching” in order to achieve “structures such as e.g. trenches, grooves, holes, vias, etc. in” “aluminum oxide (Al2O3) substrates (e.g. sapphire substrates or ruby substrates), diamond substrates”) for the unspecified patterning technique of Earney et al., and the results of the substitutions would have been predictable. Therefore it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention that silicone adhesive have properties (e.g., non-fluorescent and transparent) and to provide a known conventional patterned solid host material (e.g., comprising details such as the inorganic crystalline fluorophore comprising a natural or synthetic gemstone affixed to the holder via a non-fluorescent transparent adhesive, wherein the fiducial marker is etched on the inorganic crystalline fluorophore) as the unspecified patterned solid host material of Earney et al. In regard to claim 2 which is dependent on claim 1, Earney et al. also disclose that the photostable fluorescence balancing target is usable to balance each wavelength channel of a multi-detector microscopy system (e.g., “… inspection apparatus 100 may be utilized in connection with calibration of standard consumer optical tools such as fluorescence microscopes … fluorescing material emits in one or more emission channels of interest …” in paragraphs 48 and 54). In regard to claim 3 which is dependent on claim 1, Earney et al. also disclose that a length, a width, and a depth of the holder are based on a sample holder of a microscope system (e.g., “… inspection apparatus 100 may be utilized in connection with calibration of standard consumer optical tools such as fluorescence microscopes …” in paragraph 48). In regard to claim 4 which is dependent on claim 1, Earney et al. also disclose that the inorganic crystalline fluorophore includes a transition metal dopant (e.g., “… optical target 120 represents a solid body structure that includes a solid host material and a fluorescing material embedded within the solid host material … solid host material may include at least one of … crystalline materials … fluorescing material may be a rare-earth element such as rare earth ions: Tm3+ (455 nm), Ho3+ (550 nm), Tb3+ (540 nm), Eu3+ (611 nm), Sm3+ (550 nm), Pr3+ (488, 590 nm), Dy3+ (480 nm & 575 nm), or Er3+ (550 nm & 660 nm); an element from the Actinide series: U; transition metal ions: Ti3+, Cr2+/3+ etc. … fluorescing material emits in one or more emission channels of interest …” in paragraphs 52-54). In regard to claim 5 which is dependent on claim 1, Earney et al. also disclose that the inorganic crystalline fluorophore is doped with chromium (e.g., “… optical target 120 represents a solid body structure that includes a solid host material and a fluorescing material embedded within the solid host material … solid host material may include at least one of … crystalline materials … fluorescing material may be a rare-earth element such as rare earth ions: Tm3+ (455 nm), Ho3+ (550 nm), Tb3+ (540 nm), Eu3+ (611 nm), Sm3+ (550 nm), Pr3+ (488, 590 nm), Dy3+ (480 nm & 575 nm), or Er3+ (550 nm & 660 nm); an element from the Actinide series: U; transition metal ions: Ti3+, Cr2+/3+ etc. … fluorescing material emits in one or more emission channels of interest …” in paragraphs 52-54). In regard to claim 6 which is dependent on claim 1, the target of Earney et al. lacks an explicit description of details of the “… solid host material …” such as the inorganic crystalline fluorophore is ruby. However, “… solid host material …” details are known to one of ordinary skill in the art (e.g., see “… commercially available: diamond, silicon carbide (moissanite), ruby, sapphire, zircon, beryl, emerald, opal, quartz, jade, topaz, turquoise, lapis lazuli, chrysoberyl, amber, spine!, tourmaline, tanzanite, zincblende, wurtzite, and others …” in paragraph 36 of Haberstroh et al.). It should be noted that “when a patent claims a structure already known in the prior art that is altered by the mere substitution of one element for another known in the field, the combination must do more than yield a predictable results”. KSR International Co. v. Teleflex Inc., 550 U.S. 398 at 416, 82 USPQ2d 1385 (2007) at 1395 (citing United States v. Adams, 383 U.S. 39, 40 [148 USPQ 479] (1966)). See MPEP § 2143. In this case, one of ordinary skill in the art could have substituted a known conventional solid host material (e.g., comprising details such as “commercially available” “ruby”) for the unspecified solid host material of Earney et al. and the results of the substitution would have been predictable. Therefore it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to provide a known conventional solid host material (e.g., comprising details such as the inorganic crystalline fluorophore is ruby) as the unspecified solid host material of Earney et al. In regard to claim 7 which is dependent on claim 1, Earney et al. also disclose that the inorganic crystalline fluorophore absorbs and emits multiple wavelengths of visible light (e.g., “… optical target 120 represents a solid body structure that includes a solid host material and a fluorescing material embedded within the solid host material … solid host material may include at least one of … crystalline materials … fluorescing material may be a rare-earth element such as rare earth ions: Tm3+ (455 nm), Ho3+ (550 nm), Tb3+ (540 nm), Eu3+ (611 nm), Sm3+ (550 nm), Pr3+ (488, 590 nm), Dy3+ (480 nm & 575 nm), or Er3+ (550 nm & 660 nm); an element from the Actinide series: U; transition metal ions: Ti3+, Cr2+/3+ etc. … fluorescing material emits in one or more emission channels of interest …” in paragraphs 52-54). In regard to claim 8 which is dependent on claim 1, Earney et al. also disclose that the fiducial marker is one of a plurality of fiducial markers positioned on the inorganic crystalline fluorophore for redundancy (e.g., “… instrument moves the objective to the auto centering fiducial and performs an XY stage position repeatability test. The instrument moves the X and Y stage multiple times from each direction to the auto centering fiducial and after each move it takes an image of the auto centering fiducial. Ideally, the auto centering fiducial would show up at exactly the same position in the image after every move …” in paragraph 159), and the plurality of fiducial markers are labeled (e.g., see 280 and 282 in Fig. 2D). Alternatively it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention that one of the pictorial labels 280 and 282 in Fig. 2D of Earney et al. is selected to be “the auto centering fiducial”. Allowable Subject Matter Claim(s) 9-13 and 15-21 is/are allowed. The following is a statement of reasons for the indication of allowable subject matter: the instant application is deemed to be directed to a nonobvious improvement over the invention disclosed in US 2006/0109475 (the improvement comprises in combination with other recited elements, wherein the pixel area is centered on the fiducial marker as recited in independent claim 9) and the instant application is deemed to be directed to a nonobvious improvement over the invention disclosed in US 2021/0055224 (the improvement comprises in combination with other recited elements, wherein the balancing includes adjusting an intensity of an emission source of one or more wavelength channels of the n wavelength channels such that each wavelength channel of the n wavelength channels generates images having similar intensities while maintaining a respective exposure time for each wavelength channel constant during the balancing, wherein the respective exposure time for each wavelength channel during the balancing is set based on an identity of the inorganic crystalline fluorophore as recited in independent claim 15). Response to Arguments Applicant’s arguments with respect to the amended and new claims have been fully considered but some are moot in view of the new ground(s) of rejection. Applicant's remaining arguments filed 3 June 2026 have been fully considered but they are not persuasive. Applicant argues that the combination of the cited prior art fails to disclose or suggest “a fiducial marker positioned on the inorganic crystalline fluorophore, wherein the fiducial marker is etched on the inorganic crystalline fluorophore” as recited in claim 1 because Earney et al.‘s teaching of “… grating structure may be patterned directly on the solid fluorescing substrate (e.g., see FIG. 2E) to form a monolithic structure …” refers to a grating structure and not a fiducial marker. Examiner respectfully disagrees. Earney et al. state (paragraph 75) that “… grating layer 122 may have different regions to be used in connection with different types of alignment operations and/or calibration tests … By way of example, the grating layer 122 may include one or more image quality tiles, distortion tiles, clear tiles, fiducials and the like. The objective is positioned relative to various tiles to collect information in connection with performing various tests … upper and/or lower surface of the grating layer 122, where the upper and lower surfaces are designated relative to the objective of the instrument. For example, the upper surface represents the surface that is proximate to the objective, while the lower surface represents the surface that is distal from the objective. Alternately, the grating structure may be patterned directly on the solid fluorescing substrate (e.g., see FIG. 2E) to form a monolithic structure …”. Thus the “fiducial marker” as recited in claim 1 is taught or suggested by the “grating layer 122 may include one or more image quality tiles, distortion tiles, clear tiles, fiducials and the like” with “the grating structure may be patterned directly on the solid fluorescing substrate (e.g., see FIG. 2E) to form a monolithic structure” of Earney et al. Therefore, the combination of the cited prior art teaches or suggests all limitations as arranged in the claims. Applicant argues that the combination of the cited prior art fails to disclose or suggest “a fiducial marker positioned on the inorganic crystalline fluorophore, wherein the fiducial marker is etched on the inorganic crystalline fluorophore” as recited in claim 1 because Earney et al. require moving the fiducial markers from the grating layer to the optical target itself. Examiner respectfully disagrees. Earney et al. teach at least one embodiment of an “optical target 120” and a “microstructure 123 may be provided as a solid layer with the predetermined pattern represented by opening or gaps through the microstructure 123 that form channels, pin holes, and the like” configured as “fiducials and the like” on “upper and/or lower surface of the grating layer 122” (e.g., see “… grating layer 122 may have different regions to be used in connection with different types of alignment operations and/or calibration tests … By way of example, the grating layer 122 may include one or more image quality tiles, distortion tiles, clear tiles, fiducials and the like. The objective is positioned relative to various tiles to collect information in connection with performing various tests … grating layer 122 may be formed from a clear carrier substrate (e.g., glass) with various microstructures 123 provided thereon and shaped in one or more predetermined patterns … Optionally, the microstructure 123 may be provided as a solid layer with the predetermined pattern represented by opening or gaps through the microstructure 123 that form channels, pin holes, and the like. The micro­structure 123 may be provided on an upper and/or lower surface of the grating layer 122, where the upper and lower surfaces are designated relative to the objective of the instrument. For example, the upper surface represents the surface that is proximate to the objective, while the lower surface represents the surface that is distal from the objective. Alternately, the grating structure may be patterned directly on the solid fluorescing substrate (e.g., see FIG. 2E) to form a monolithic structure …” in paragraph 75). Earney et al. also teach at least one “monolithic structure” embodiment of “opening or gaps through the microstructure 123 that form channels, pin holes, and the like” configured as “fiducials and the like” on “upper and/or lower surface” of “the solid fluorescing substrate”. It is important to recognize that monolithic is defined1 as “consisting of one piece; solid or unbroken”. Thus the “fiducial marker” as recited in claim 1 is taught or suggested by “the grating structure may be patterned directly on the solid fluorescing substrate (e.g., see FIG. 2E) to form a monolithic structure” of Earney et al. Therefore, the combination of the cited prior art teaches or suggests all limitations as arranged in the claims. Applicant argues that the combination of the cited prior art fails to disclose or suggest “a fiducial marker positioned on the inorganic crystalline fluorophore, wherein the fiducial marker is etched on the inorganic crystalline fluorophore” as recited in claim 1 because Earney et al. require changing the method of forming the fiducials from chrome deposition to plasma etching. Examiner respectfully disagrees. It is important to recognize that the key phrase “Optionally” in “Optionally, the microstructure 123 may be provided as a solid layer with the predetermined pattern represented by opening or gaps through the microstructure 123 that form channels, pin holes, and the like” of Earney et al. teaches optional microstructure embodiments without chrome deposition. Therefore, the combination of the cited prior art teaches or suggests all limitations as arranged in the claims. Applicant argues that ruby is itself a fluorophore (Al2O3:Cr3+). Examiner respectfully disagrees. Initially, applicant's arguments that ruby is itself a fluorophore (Al2O3:Cr3+) is not persuasive because applicant fails to provide any evidence or even any explanation. Earney et al. teach (paragraph 54) that “… fluorescing material may be … Cr2+/3+ etc. … fluorescing material may be distributed in an even and homogeneous fixed manner throughout the solid host material …” wherein (paragraph 53) “… the solid host material may include at least one of glass, amorphous polymers, crystalline materials, semi-crystalline polymers, metallic glass, ceramic and the like …”. Further Engelhardt teaches (paragraph 176 ) “… aluminum oxide (Al2O3) substrates (e.g. sapphire substrates or ruby substrates) …” and Haberstroh et al. teach (paragraph 36) “… commercially available: … ruby …”. One of ordinary skill in the art could have substituted a known conventional solid host material (e.g., comprising details such as “commercially available” “ruby”) for the unspecified “solid host material may include at least one of glass, amorphous polymers, crystalline materials, semi-crystalline polymers, metallic glass, ceramic and the like” of Earney et al. and the results of the substitution would have been predictable. Therefore, the combination of the cited prior art teaches or suggests all limitations as arranged in the claims. Conclusion The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Malíčková et al. (Laser effect in the optical luminescence of oxides containing Cr, Acta Geologica Slovaca, Vol. 10, no. 1, 2018, pp. 27-34) teach Ruby properties. THIS ACTION IS MADE FINAL. 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 Shun Lee whose telephone number is (571)272-2439. The examiner can normally be reached Monday-Friday. 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, Uzma Alam can be reached at (571)272-3995. 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. /SL/ Examiner, Art Unit 2884 /UZMA ALAM/Supervisory Patent Examiner, Art Unit 2884 1 Random House Kernerman Webster's College Dictionary, © 2010 K Dictionaries Ltd. Copyright 2005, 1997, 1991 by Random House, Inc. All rights reserved.
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Prosecution Timeline

Show 1 earlier event
Apr 16, 2025
Non-Final Rejection mailed — §103
Jul 16, 2025
Response Filed
Aug 22, 2025
Final Rejection mailed — §103
Dec 22, 2025
Request for Continued Examination
Jan 14, 2026
Response after Non-Final Action
Mar 03, 2026
Non-Final Rejection mailed — §103
Jun 03, 2026
Response Filed
Aug 26, 2026
Final Rejection mailed — §103 (current)

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Prosecution Projections

5-6
Expected OA Rounds
42%
Grant Probability
58%
With Interview (+16.3%)
3y 6m (~2m remaining)
Median Time to Grant
High
PTA Risk
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