Prosecution Insights
Last updated: April 19, 2026
Application No. 18/377,236

CHEMICALLY REVERSIBLE 2`-OH ACYLATION PROTECTS RNA FROM HYDROLYTIC AND ENZYMATIC DEGRADATION

Non-Final OA §102§112
Filed
Oct 05, 2023
Examiner
LEWIS, PATRICK T
Art Unit
1691
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
The Board Of Trustees Of The Leland Stanford Junior University
OA Round
1 (Non-Final)
74%
Grant Probability
Favorable
1-2
OA Rounds
2y 6m
To Grant
89%
With Interview

Examiner Intelligence

Grants 74% — above average
74%
Career Allow Rate
844 granted / 1135 resolved
+14.4% vs TC avg
Moderate +14% lift
Without
With
+14.3%
Interview Lift
resolved cases with interview
Typical timeline
2y 6m
Avg Prosecution
40 currently pending
Career history
1175
Total Applications
across all art units

Statute-Specific Performance

§101
4.0%
-36.0% vs TC avg
§103
30.5%
-9.5% vs TC avg
§102
20.4%
-19.6% vs TC avg
§112
21.4%
-18.6% vs TC avg
Black line = Tech Center average estimate • Based on career data from 1135 resolved cases

Office Action

§102 §112
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 Regarding claim 1, 4, and dependent claims thereof, including claims 23-25, step (b) is optional and is not required step to meet the limitations of the claimed invention. Regarding claim 8, 11, 15, 21, and dependent claims thereof, optional elements (e.g., “where the poly(A) tail of the mRNA is selectively acylated”) are not required to meet the limitations of the claimed invention. Regarding the clause “wherein at least…after step (a)” in claims 18-20 and “wherein the acylation…a cell environment” in claim 26, claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure. A “wherein” clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited. See MPEP 2111.04. 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. Claim 3 is 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. The clause “wherein R is selected from…and PNG media_image1.png 58 164 media_image1.png Greyscale ” renders the claim indefinite as claim 1 does not recite a structure containing a variable R. Thus, it would have been unclear to one of ordinary skill if applicant intends for the invention to be limited by a structure containing variable R. 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. Claim(s) 1-3, 15, 18, 20-21, and 23-26 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Velema, Willem A., and Eric T. Kool. "The chemistry and applications of RNA 2′-OH acylation." Nature Reviews Chemistry 4.1 (2020): 22-37 (Velema). Velema teaches that the direct functionalization of RNA by selective acylation of the 2′-hydroxyl (2′-OH) group has emerged as a powerful alternative that enables the simple modification of both synthetic and transcribed RNAs (Abstract). Velema teaches the chemical properties and design of effective reagents for RNA 2′-OH acylation, highlighting the unique problem of 2′-OH reactivity in the presence of water. Velema teaches that the concept of reversible acylation opens up multiple opportunities in application (page 18). For example, the resurgence of RNA as pharmacotherapy has led to increased efforts in the discovery of new technologies for intracellular delivery. The possibility of covalently attaching delivery and targeting scaffolds to RNA through 2′-OH acylation is a potentially attractive strategy to enhance cellular uptake of RNA. The combination of reversible acylation with existing technologies that rely on RNA activity are likely to become powerful methods for biological studies. For example, chemically or optically reversible acylation might serve as a general system to gain temporal control over RNA folding and function. Velema discloses, as RNA is highly soluble in water and poorly soluble in most organic solvents, the majority of acylating reactions are performed under aqueous conditions (page 4). Thus, water is assumed to be the de facto solvent in the Review, unless otherwise stated. Velema further discloses a scheme of the RNA acylation and phosphine-mediated deacylation reaction (Fig. 7a, page 33). PNG media_image2.png 234 954 media_image2.png Greyscale Thus, Velema teaches a method comprising a) contacting RNA with an imidazole (e.g., PNG media_image3.png 114 136 media_image3.png Greyscale ) in an aqueous solution. Velema teaches all of the instantly claimed elements. Thus, claims 1-3, 15, 18, 20-21, and 23-26 are anticipated. Conclusion Claims 1-4, 6-8, 10-11, 13-15, 18-21, and 23-26 are pending. Claims 1-3, 15, 18, 20-21, and 23-26 are rejected. Claims 8, 10-11, 13-14, and 19 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims. Claims 4 and 6-7 are allowed. The following is a statement of reasons for the indication of allowable subject matter: Velema, Willem A., and Eric T. Kool. "The chemistry and applications of RNA 2′-OH acylation." Nature Reviews Chemistry 4.1 (2020): 22-37 (Velema) is representative of prior art. Velema does not teach or suggest a method comprising contacting RNA with a sulfonylation agent. Contacts Any inquiry concerning this communication or earlier communications from the examiner should be directed to PATRICK T LEWIS whose telephone number is (571)272-0655. The examiner can normally be reached Monday to Friday, 10 AM to 4 PM EST (Maxi Flex). 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, Renee Claytor can be reached at (571) 272-8394. 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. /PATRICK T LEWIS/Primary Examiner, Art Unit 1691 /PL/
Read full office action

Prosecution Timeline

Oct 05, 2023
Application Filed
Mar 02, 2026
Non-Final Rejection — §102, §112 (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

1-2
Expected OA Rounds
74%
Grant Probability
89%
With Interview (+14.3%)
2y 6m
Median Time to Grant
Low
PTA Risk
Based on 1135 resolved cases by this examiner. Grant probability derived from career allow rate.

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