Prosecution Insights
Last updated: August 16, 2026
Application No. 18/554,819

NON-COVALENT HALOTAG LIGANDS

Non-Final OA §103
Filed
Oct 11, 2023
Priority
Apr 30, 2021 — EU 21171702.0 +2 more
Examiner
CHAO, ALLEN
Art Unit
1622
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
Max-planck-gesellschaft Zur Förderung der Wissenschaften E.v.
OA Round
1 (Non-Final)
67%
Grant Probability
Favorable
1-2
OA Rounds
2m
Est. Remaining
67%
With Interview

Examiner Intelligence

Grants 67% — above average
67%
Career Allowance Rate
4 granted / 6 resolved
+6.7% vs TC avg
Minimal +0% lift
Without
With
+0.0%
Interview Lift
resolved cases with interview
Typical timeline
3y 0m
Avg Prosecution
63 currently pending
Career history
40
Total Applications
across all art units

Statute-Specific Performance

§101
1.1%
-38.9% vs TC avg
§103
41.9%
+1.9% vs TC avg
§102
22.6%
-17.4% vs TC avg
§112
25.8%
-14.2% vs TC avg
Black line = Tech Center average estimate • Based on career data from 6 resolved cases

Office Action

§103
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 . DETAILED ACTION This office action is in reply to the election response filed on 03 April 2026 for application 18/554,819 which was filed 11 October 2023, 371 of PCT/EP2022/061679 filed on 02 May 2022, claiming priority from EP21205120.5 filed on 27 October 2021 and EP 21171702.0 filed on 30 April 2021. Claims 1-2, 4 and 6-7 are amended. Currently, claims 1-15 are pending. Priority Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. Information Disclosure Statement The information disclosure statement (IDS) submitted on 11 October 2023 was filed on the mailing date of the application on 11 October 2023. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner. Election/Restrictions Applicant’s election of Group I, encompassing claims 1-8 is acknowledged. Applicant’s election of compound SiR-25 of general formula (I) and pictured as SiR-T5 is acknowledged: PNG media_image1.png 260 197 media_image1.png Greyscale Applicant informs that claims 1-2 and 4-7 read upon this election. Claims 3 and 8-15 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention or species, there being no allowable generic or linking claim. The elected species was searched and found to be free of the prior art. The closest match is SiR-Halo as described by Zheng et al. (Rational design of fluorogenic and spontaneously blinking labels for super-resolution imaging, ACS Cent. Sci. 2019, 5, 1602-1613) as described by compound 8HTL: PNG media_image2.png 304 269 media_image2.png Greyscale Conceptually, non-covalent binding halotag ligands were described by Hirose et al. (Novel fluorescent labeling method, US 2020/0199174 A1, 2020), but utilizes 3,5-dinitrophenyl (DNP) and other analogous aryl groups, including fluorinated substituents, as the non-binding moiety: PNG media_image3.png 226 575 media_image3.png Greyscale 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 non-obviousness. Claims 1-2 and 4-7 are rejected under 35 U.S.C. 103 as being unpatentable over Zheng et al. (Rational design of fluorogenic and spontaneously blinking labels for super-resolution imaging, ACS Cent. Sci. 2019, 5, 1602-1613) in view of Murrey et al. (Systematic evaluation of biorthogonal reactions in live cells with clickable halotag ligands: implications for intracellular imaging, J. Am. Chem. Soc. 2014, 137, 11461-11475). Zheng discloses compound 8HTL: PNG media_image2.png 304 269 media_image2.png Greyscale Zheng does not, however, disclose other groups aside from chloride as the irreversibly reactive moiety. Murrey rectifies this deficiency by teaching biorthogonal reactions for application in halotag ligands, including the strain-promoted azide-alkyne cycloaddition and inverse electron demand diels-alder including utilizing azide 3 as a chemically inert group under cellular conditions except under click-reaction catalysis, in this case exemplified by use in conjunction with TAMRA 12, a similar rhodamine fluorophore: PNG media_image4.png 349 469 media_image4.png Greyscale With Murray’s teaching, general formula (I) D-L-T is satisfied where D is a fluorescent organic dye moiety characterized by a molecular mass of between 300 g/mol and 1300 g/mol, L is a linear linker of 10-15 atoms in length wherein L comprises alkyl or ether moieties, and T is an azide. As such, it would have been prima facie obvious, to a person of ordinary skill in the art, to consider incorporating the teachings of Murray of terminal azide groups onto the compound 8HTL as disclosed by Zheng. Regarding the limitations of claim 2, where the selection of T from general formula (I) now includes hydroxyl, is still met by Zheng and Murrey. Concerning the limitations of claim 4, wherein D comprises a linking moiety X which connects the functional moiety Z to L, wherein X is selected from an amide, a secondary amine, a 1,2,3-triazole, an ester, a sulfonamide, an ether, a thioether, a thiourea, a urea, and a carbamate, are met as the linking moiety in compound 8HTL is an amide. With respect to the limitations of claim 5, wherein L is a linear unbranched alkyl chain, comprising 1, 2, or 3 moieties independently selected from ether and trans-alkylene, are met as compound 8HTL includes 2 ether moieties. With regards to the limitations of claim 6, wherein the compound is characterized by the one of the general formulas (II), (III), (IV), (V), or (VI), are met as compound 8HTL reads upon general formula (II) where n = 3. With concern to the limitations of claim 7, wherein Z is a fluorophore selected from a rhodamine, a silicon rhodamine, a fluorescein, a Janelia Fluor dye, an olefinic silicon rhodamine derivative with an exocyclic double bond, a MaP dye, a carbopyronine, a carbocyanine (particularly a Cy3 or a Cy5 dye), a pyrene, a Bodipy fluorophore, a coumarine, a rhodol, and an Alexa dye, are met as compound 8HTL includes a silicon rhodamine. Allowable Subject Matter The following is a statement of reasons for the indication of allowable subject matter: elected species SiR-25 was found to be free of the prior art. PNG media_image1.png 260 197 media_image1.png Greyscale The closest match is SiR-Halo as described by Zheng et al. (Rational design of fluorogenic and spontaneously blinking labels for super-resolution imaging, ACS Cent. Sci. 2019, 5, 1602-1613) as described by compound 8HTL: PNG media_image2.png 304 269 media_image2.png Greyscale Summary Claims 1-2 and 4-7 are rejected under 35 U.S.C. 103. Elected species SiR-25 including SiR-S5 and SiR-T5 were found to be free of the prior art. Conclusion No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Allen Chao whose telephone number is (571)272-7001. The examiner can normally be reached Monday - Friday 0700-1300. 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, James H Alstrum-Acevedo can be reached at 571-272-5548. 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. /ALLEN CHAO/Examiner, Art Unit 1622 /JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
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Prosecution Timeline

Oct 11, 2023
Application Filed
May 14, 2026
Non-Final Rejection mailed — §103
Jul 31, 2026
Interview Requested
Aug 06, 2026
Examiner Interview Summary

Precedent Cases

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INHIBITORS OF HPK1 AND METHODS OF USE THEREOF
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Study what changed to get past this examiner. Based on 1 most recent grants.

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Prosecution Projections

1-2
Expected OA Rounds
67%
Grant Probability
67%
With Interview (+0.0%)
3y 0m (~2m remaining)
Median Time to Grant
Low
PTA Risk
Based on 6 resolved cases by this examiner. Grant probability derived from career allowance rate.

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