Prosecution Insights
Last updated: April 19, 2026
Application No. 18/031,602

STABILIZED NOROVIRUS VIRUS-LIKE PARTICLES AS VACCINE IMMUNOGENS

Non-Final OA §112
Filed
Apr 12, 2023
Examiner
BOESEN, AGNIESZKA
Art Unit
1672
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
BOARD OF REGENTS OF THE UNIVERSITY OF TEXAS SYSTEM
OA Round
1 (Non-Final)
68%
Grant Probability
Favorable
1-2
OA Rounds
3y 4m
To Grant
90%
With Interview

Examiner Intelligence

Grants 68% — above average
68%
Career Allow Rate
555 granted / 816 resolved
+8.0% vs TC avg
Strong +22% interview lift
Without
With
+22.5%
Interview Lift
resolved cases with interview
Typical timeline
3y 4m
Avg Prosecution
31 currently pending
Career history
847
Total Applications
across all art units

Statute-Specific Performance

§101
6.9%
-33.1% vs TC avg
§103
31.6%
-8.4% vs TC avg
§102
20.7%
-19.3% vs TC avg
§112
21.3%
-18.7% vs TC avg
Black line = Tech Center average estimate • Based on career data from 816 resolved cases

Office Action

§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. Election/Restrictions Applic ant's election with out traverse of Group I, claims 1-30 and 35 in the reply filed on January 29, 2026 is acknowledged. Claims 31, 32, 33, 34, and 36-44 are withdrawn as being drawn to non-elected invention. Claims 1-30 and 35 are under examination in this Office action. Information Disclosure Statement The information disclosure statement (IDS) submitted on April 12, 2023 has been considered by the examiner. Claim Rejections - 35 USC § 112 The following is a quotation of the first paragraph of 35 U.S.C. 112(a): (a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention. The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112: The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention. Claims 3, 9, 10 , 1 3 and 20-21 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had posses sion of the claimed invention . Claims 3, 9, 10 and 13 lack structure and function correlation and are therefore rejected for lack of written description. The claims require a recombinant Norovirus VLP while they recite a partial structure of the said VLP . The claims are open to unlimited number of amino acids substitutions while requiring that the cysteine substitutions form a non-natural interprotomer disulfide bond. The present claims lack structure and function correlation. Claim 3 recites: The recombinant Norovirus VLP of claim 2, wherein the recombinant Norovirus GI VP1 protein comprises the amino acid substitutions and an amino acid sequence at least 90% identical to any one of SEQ ID NOs: 1-6. Claim 9 is drawn to : The recombinant Norovirus VLP of claim 2, wherein the recombinant Norovirus GI VP1 protein is a GI.1, GI.2, GI.3, GI.4, GI.7, or GI.8 VP1 protein comprising the one or more amino acid substitutions. Claim 10 is drawn to The recombinant Norovirus VLP of claim 9, wherein the recombinant Norovirus GI VP1 protein is a GI.1 VP1 protein comprising the one or more amino acid substitutions. Claim 10 thus recites additional amino acid substitutions that are outside the genus of present claim 1. Claim 13 is drawn to The recombinant Norovirus VLP of claim 12, wherein the recombinant Norovirus GII VP1 protein comprises the amino acid substitutions and an amino acid sequence at least 90% identical to any one of SEQ ID NOs: 26-51. Claim 13 fails to further limit claim 1 and claim 12. Claim 20 is drawn to The recombinant Norovirus VLP of claim 12, wherein the recombinant Norovirus GII VP1 protein is a GII.1, GII.2, GII.3, GII.4, GII.4c, GII.5, GII.6, GII.7, GII.8, GII.9, GII.10, GII.11, GII.12, GII.13, GII.14, GII.15, GII.16, GII.17, GII.18, GII.19, GII.20, GII.21, GII.22, GII.23, GII.24, or GII.25 VP1 protein comprising the one or more amino acid substitutions. Claim 21 is drawn to The recombinant Norovirus VLP of claim 12, wherein the recombinant Norovirus GII VP1 protein is a GII.4c VP1 protein comprising the one or more amino acid substitutions. Independent Claim 1 is limited to the amino acid substitutions selected from the group consisting of N116C/G193C, A37C/A44C, Q62C/A140C, L144C/P221C, G131C/N172C, and N167C/L169C relative to SEQ ID NO: 1 , and selected amino acid substitutions selected from N112C/A116C, N189C/D194C, P60C/S134C, M140C/P217C, P129C/R223C relative to SEQ ID NO: 51, while the dependent claim s 3, 9, 10 and 13 are broader in scope and recite unlimited number of amino acid substitutions and partial sequence similarity, of at least 90% identical to any one of SEQ ID NOs: 1-6 and at least 90% identical to any one of SEQ ID NOs: 26-51. Applicant’s specification describes recombinant Norovirus VLP comprises a multimer of a recombinant Norovirus GI VP1 protein comprising amino acid substitutions set forth as one or more of the following pairs of cysteine substitutions that form a non-natural interprotomer disulfide bond: N116C/G193C, A37C/A44C, Q62C/A140C, L144C/P221C, G131C/N172C, and N167C/L169C, and/or one or more of the following pairs of hydrophobic amino acid substitutions: Q141V/P221L and A37I/A44L substitutions, wherein the amino acid positions are according to the reference GI VP1 protein sequence set forth as SEQ ID NO: 1. In some embodiments, the recombinant Norovirus VLP comprises a multimer of a recombinant Norovirus GII VP1 protein comprising amino acid substitutions set forth as one or more of the following pairs of cysteine substitutions that form a non-natural interprotomer disulfide bond: N112C/A116C, N189C/D194C, P60C/S134C, M140C/P217C, P129C/R223C, wherein the amino acid positions are according to the reference GII VP1 protein sequence set forth as SEQ ID NO: 51. FIG. 20 in Applicant’s specification shows s creening of GI14.4c stabilizing mutations . Baculoviruses harboring each clone were used to infect small-scale (50 mL) insect cell cultures for four days at 27C. Supernatants were collected and incubated with 20 mM diamide for 1 hour at room temp. Twenty microliters of each supernatant were run on SDS-PAGE gels. Thirty-three constructs were evaluated in reducing (top gels) and non-reducing (bottom-gels) conditions. Constructs containing cysteine mutations are marked with an asterisk. Boxes indicate promising candidates. Applicant’s specification identifies particular cysteine mutations that allow the Norovirus VLP to form while stabilizing the VLP structure. Applicant’s claims are drawn to a genus of VLPs that contain an unlimited number of mutations. The claims lack written description support because there is lack of an adequate written description support for the genus of mutations encompassed by the present claims. Claims 3, 9, 10 , 13 and 20-21 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends , or for failing to include all the limitations of the claim upon which it depends. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements. Claim 3 recites: The recombinant Norovirus VLP of claim 2, wherein the recombinant Norovirus GI VP1 protein comprises the amino acid substitutions and an amino acid sequence at least 90% identical to any one of SEQ ID NOs: 1-6. Claim 3 f ails to further limit claims 1 and 2 . Claim 1 is limited to the amino acid substitutions selected from the group consisting of N116C/G193C, A37C/A44C, Q62C/A140C, L144C/P221C, G131C/N172C, and N167C/L169C relative to SEQ ID NO: 1 , and selected amino acid substitutions selected from N112C/A116C, N189C/D194C, P60C/S134C, M140C/P217C, P129C/R223C relative to SEQ ID NO: 51 , while the dependent claim 3 requires additional amino acid substitutions within an amino acid sequence at least 90% identical to any one of SEQ ID NOs 1-6 . Claim 3 depends from claim 2 that is drawn to a multimer of the recombinant Norovirus G1 VP1. It is the Examiners interpretation of the claims that a multimer contains multiple copies of the Norovirus VLP as recited in present claim 1. Claim 3 thus fails to further limit present claims 1 and 2. Claim 9 is drawn to The recombinant Norovirus VLP of claim 2, wherein the recombinant Norovirus GI VP1 protein is a GI.1, GI.2, GI.3, GI.4, GI.7, or GI.8 VP1 protein comprising the one or more amino acid substitutions. Claim 9 fails to further limit present claims 1 and 2 . Claim 1 is limited to the amino acid substitutions selected from the group consisting of N116C/G193C, A37C/A44C, Q62C/A140C, L144C/P221C, G131C/N172C, and N167C/L169C relative to SEQ ID NO: 1 , and selected amino acid substitutions selected from N112C/A116C, N189C/D194C, P60C/S134C, M140C/P217C, P129C/R223C relative to SEQ ID NO: 51 , while the dependent claim 9 requires GI.2, GI.3, GI.4, GI.7, or GI.8 VP1 protein comprising the one or more amino acid substitutions. Claim 9 depends from claim 2 that is drawn to a multimer of the recombinant Norovirus G1 VP1. It is the Examiners interpretation of the claims that a multimer contains multiple copies of the Norovirus VLP as recited in present claim 1. Claim 9 thus fails to further limit present claims 1 and 2. Claim 10 is drawn to The recombinant Norovirus VLP of claim 9, wherein the recombinant Norovirus GI VP1 protein is a GI.1 VP1 protein comprising the one or more amino acid substitutions. Claim 10 thus recites additional amino acid substitutions that are outside the scope of present claim 1. Claim 13 is drawn to The recombinant Norovirus VLP of claim 12, wherein the recombinant Norovirus GII VP1 protein comprises the amino acid substitutions and an amino acid sequence at least 90% identical to any one of SEQ ID NOs: 26-51. Claim 13 f ails to further limit claim 1 and claim 12. Claim 20 is drawn to The recombinant Norovirus VLP of claim 12, wherein the recombinant Norovirus GII VP1 protein is a GII.1, GII.2, GII.3, GII.4, GII.4c, GII.5, GII.6, GII.7, GII.8, GII.9, GII.10, GII.11, GII.12, GII.13, GII.14, GII.15, GII.16, GII.17, GII.18, GII.19, GII.20, GII.21, GII.22, GII.23, GII.24, or GII.25 VP1 protein comprising the one or more amino acid substitutions. Claim 21 is drawn to The recombinant Norovirus VLP of claim 12, wherein the recombinant Norovirus GII VP1 protein is a GII.4c VP1 protein comprising the one or more amino acid substitutions. Claims 20 and 21 fail to further limit present claim 12. Correction is required. Pertinent references: Ming Xia et al. (Acs Nano, November 2018, Vol. 12, p. 10665-10682 in IDS on 4/12/2023) disclose a fusion between part of NoV VP1. Ming Xia teaches (Figures 2, 6, Discussion) cysteine substitutions introduced into the NoV VP1 part of the fusion which stabilize the VLP-like particle. The VP1 sequence in Ming Xia (see Fig. 2), contains the Q58C mutation corresponding to the Q62C mutation according to claim 1 (in present SEQ ID NO: 1). Ming Xia fails to disclose pairs of cysteine substitutions as required by the present claims. Estes et al. (US Patent 6,572,862) disclose an amino acid sequence identical with present SEQ ID NO: 1. They fail to disclose the N116C/G193C, A37C/A44C, Q62C/A140C, L144C/P221C, G131C/N172C, and N167C/L169C mutations. Richardson et al. (US Patent 8,841,120) disclose an amino acids sequence identical with present SEQ ID NO: 51. They fail to disclose any of the N112C/A116C, N189C/D194C, P60C/S134C, M140C/P217C, P129C/R223C mutations. Contact Information Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT AGNIESZKA BOESEN whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)272-8035 . The examiner can normally be reached on FILLIN "Work Schedule?" \* MERGEFORMAT 8:30 - 5:00 PM . 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, Thomas Visone can be reached on 571-270-0684. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /AGNIESZKA BOESEN/ Primary Examiner, Art Unit 1648
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Prosecution Timeline

Apr 12, 2023
Application Filed
Mar 21, 2026
Non-Final Rejection — §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
68%
Grant Probability
90%
With Interview (+22.5%)
3y 4m
Median Time to Grant
Low
PTA Risk
Based on 816 resolved cases by this examiner. Grant probability derived from career allow rate.

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