Prosecution Insights
Last updated: April 19, 2026
Application No. 18/042,517

CODON OPTIMIZED RPGRORF15 GENES AND USES THEREOF

Non-Final OA §DP
Filed
Feb 22, 2023
Examiner
MCCORMICK, CATHERINE LYNN
Art Unit
1638
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
4D Molecular Therapeutics Inc.
OA Round
1 (Non-Final)
52%
Grant Probability
Moderate
1-2
OA Rounds
3y 8m
To Grant
68%
With Interview

Examiner Intelligence

Grants 52% of resolved cases
52%
Career Allow Rate
15 granted / 29 resolved
-8.3% vs TC avg
Strong +17% interview lift
Without
With
+16.7%
Interview Lift
resolved cases with interview
Typical timeline
3y 8m
Avg Prosecution
34 currently pending
Career history
63
Total Applications
across all art units

Statute-Specific Performance

§101
4.5%
-35.5% vs TC avg
§103
44.6%
+4.6% vs TC avg
§102
28.3%
-11.7% vs TC avg
§112
15.6%
-24.4% vs TC avg
Black line = Tech Center average estimate • Based on career data from 29 resolved cases

Office Action

§DP
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 . Priority Acknowledgement is made of Applicants’ claim for benefit to prior filed US Provisional Application 63/073843, filed on 09/02/2020. This application claims the benefit of priority to Patent Application PCT/US2021/048267. Acknowledgement is made of Applicants’ claim for benefit to prior filed to Patent Application Number PCT/US2021/048267, filed on 08/30/2021. Information Disclosure Statement The IDS filed 02/22/2023 has been considered by the Examiner. Status of Claims Claims 42-66 are under examination. Claim 1-41 are cancelled. Double Patenting The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claims because the examined application claim is either anticipated by, or would have been obvious over, the reference claims. See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969). A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b). The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13. The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer. Claims 42-66 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4-15, 17-25 of U.S. Patent No. 11,345,930. Although the claims at issue are not identical, they are not patentably distinct from each other. Instant claim 42 is made obvious by claim 1 of U.S. Patent No. 11,345,930. Claim 1 recites a nucleic acid encoding human retinitis pigmentosa GTPase regulator (RPGR) protein of SEQ ID NO:2 (which is the same as SEQ ID NO:2 of the present application) and codon optimized for expression in humans, the nucleic acid comprising the nucleotide sequence set forth as SEQ ID NO: 1 (which is the same as SEQ ID NO:1 of the present application) or comprising a nucleotide sequence at least 95% identical thereto. The present application recites the nucleotide sequence set forth as SEQ ID NO: 1 or comprising a nucleotide sequence at least 91%. Although the claims at issue are not identical, they are not patentably distinct from each other because they both recite the nucleic acid can be the nucleotide sequence set forth as SEQ ID NO: 1. Both inventions recite a nucleic acid encoding human retinitis pigmentosa GTPase regulator (RPGR) protein of SEQ ID NO:2 and codon optimized for expression in humans. They further both read on the nucleic acid can be a sequence that is at least 95% identical to SEQ ID NO:1. Instant claim 43 is met by claim 2 of U.S. Patent No. 11,345,930. Claim 2 recites the nucleic acid as disclosed above in regard to claim 42, wherein the nucleotide sequence has a codon adaptation index of at least 0.89. Instant claim 44 is made obvious by claim 4 of U.S. Patent No. 11,345,930. Claim 4 recites the nucleic acid as disclosed above in regard to claim 42, comprising the nucleotide sequence set forth as SEQ ID NO: 1 (which is the same as SEQ ID NO:1 of the present application) or the nucleotide sequence at least 95% identical thereto is operably linked to an expression control sequence. Although the claims at issue are not identical, they are not patentably distinct from each other because they both recite the same nucleic acid comprising the nucleotide sequence set forth as SEQ ID NO: 1 operably linked to an expression control sequence. They further both read on the nucleic acid can be a sequence that is at least 95% identical to SEQ ID NO:1. Instant claim 45 is met by claim 5 of U.S. Patent No. 11,345,930. Claim 5 recites the expression cassette as disclosed above in regard to claim 44, wherein the expression control sequence is a constitutive promoter or is a promoter that directs preferential expression of the nucleic acid in rod and cone cells. Instant claim 46 is met by claim 6 of U.S. Patent No. 11,345,930. Claim 6 recites the expression cassette as disclosed above in regard to claim 45, wherein the expression control sequence is a human G protein-coupled receptor rhodopsin kinase 1 (hGRK) promoter. Instant claim 47 is met by claim 7 of U.S. Patent No. 11,345,930. Claim 7 recites the expression cassette as disclosed above in regard to claim 45. Claim 7 recites the expression cassette of claim 6, comprising from 5' to 3': (a) an AAV2 terminal repeat (b) an hGRK promoter of SEQ ID NO:4 (which is the same as SEQ ID NO:4 of the present application) (c) codon optimized RPGRorfl5 gene of SEQ ID NO:1 (which is the same as SEQ ID NO:1 of the present application) (d) an SV40 polyadenylation sequence and (e) an AAV2 terminal repeat. Instant claim 48 is met by claim 8 of U.S. Patent No. 11,345,930. Claim 8 recites the expression cassette as disclosed above in regard to claim 47. Claim 8 recites the expression cassette wherein the 5' AAV2 terminal repeat has the nucleotide sequence set forth as SEQ ID NO:6 (which is the same as SEQ ID NO:6 of the present application) and/or wherein the hGRK promoter has the nucleotide sequence set forth as SEQ ID NO:4(which is the same as SEQ ID NO:4 of the present application) and/or wherein the SV40 polyadenylation sequence has the nucleotide sequence set forth as SEQ ID NO:8 (which is the same as SEQ ID NO:8 of the present application) and/or wherein the 3' AAV2 terminal repeat has the nucleotide sequence set forth as SEQ ID NO:7 (which is the same as SEQ ID NO:7 of the present application). Instant claim 49 is made obvious by claim 9 of U.S. Patent No. 11,345,930. Claim 9 recites the expression cassette as disclosed above in regard to claim 48. Claim 9 recites the expression cassette comprising or consisting of the nucleotide sequence of SEQ ID NO:5 (which is the same as SEQ ID NO:5 of the present application) or a sequence at least at least 95% identical thereto. Although the claims at issue are not identical, they are not patentably distinct from each other because they both recite the same expression cassette comprising or consisting of the nucleotide sequence of SEQ ID NO:5. They also both read on a sequence at least at least 95% identical thereto. Instant claim 50 is met by claim 10 of U.S. Patent No. 11,345,930. Claim 10 recites recombinant adeno-associated virus (rAAV) vector comprising a heterologous nucleic acid comprising the expression cassette as disclosed above in regard to claim 44. Instant claim 51 is met by claim 11 of U.S. Patent No. 11,345,930. Claim 11 recites an rAAV vector as disclosed above in regard to claim 50. Claim 11 recites the rAAV vector comprises an AAV capsid of serotype 2, 5 or 8 or a variant thereof. Instant claim 52 is met by claim 12 of U.S. Patent No. 11,345,930. Claim 12 recites an rAAV vector as disclosed above in regard to claim 51. Claim 12 recites the rAAV vector comprises a variant AAV capsid protein comprising the amino acid sequence of SEQ ID NO:9 (which is the same as SEQ ID NO:9 of the present application). Instant claim 53 is met by claim 13 of U.S. Patent No. 11,345,930. Claim 13 recites an rAAV vector as disclosed above in regard to claim 52. Claim 13 recites the rAAV vector comprises a nucleic acid comprising from 5' to 3': (a) an AAV2 terminal repeat (b) an hGRK promoter (c) codon optimized RPGRorf15 gene of SEQ ID NO:1 (which is the same as SEQ ID NO:1 of the present application) and (d) an AAV2 terminal repeat. Instant claim 54 is met by claim 14 of U.S. Patent No. 11,345,930. Claim 14 recites an rAAV vector as disclosed above in regard to claim 53. Claim 14 recites the 5' AAV2 terminal repeat has the nucleotide sequence set forth as SEQ ID NO:6 (which is the same as SEQ ID NO:6 of the present application) and/or wherein the hGRK promoter has the nucleotide sequence set forth as SEQ ID NO:4 (which is the same as SEQ ID NO:4 of the present application) and/or wherein the SV40 polyadenylation sequence has the nucleotide sequence set forth as SEQ ID NO:8 (which is the same as SEQ ID NO:8 of the present application) and/or wherein the 3' AAV2 terminal repeat has the nucleotide sequence set forth as SEQ ID NO:7. Instant claim 55 is made obvious by claim 15 of U.S. Patent No. 11,345,930. Claim 15 recites an rAAV vector as disclosed above in regard to claim 54. Claim 15 recites the rAAV vector comprises a nucleic acid comprising the nucleotide sequence of SEQ ID NO:5 (which is the same as SEQ ID NO:5 of the present application) or a sequence at least 95% identical thereto. Although the claims at issue are not identical, they are not patentably distinct from each other because they both recite the rAAV vector comprises a nucleic acid comprising the nucleotide sequence of SEQ ID NO:5. Both read on nucleic acid comprising a nucleotide sequence at least 95% identical to SEQ ID NO:5. Instant claim 56 is met by claim 17 of U.S. Patent No. 11,345,930. Claim 17 recites a method for treating XLRP in a human subject in need thereof, comprising administering to the subject a therapeutically effective amount of pharmaceutical composition comprising an rAAV. Claim 17 recites the rAAV vector is a recombinant adeno-associated virus (rAAV) vector comprising a heterologous nucleic acid comprising the expression cassette as described above regarding claim 44. Instant claim 57 is met by claim 17 of U.S. Patent No. 11,345,930. Claim 17 recites a method for treating XLRP in a human subject in need thereof, comprising administering to the subject a therapeutically effective amount of pharmaceutical composition comprising an rAAV vector according to as disclosed above in regard to claim 53 and a pharmaceutically acceptable excipient, whereby the XLRP is treated in the human subject. Instant claim 58 is met by claim 18 of U.S. Patent No. 11,345,930. Claim 18 recites a method as disclosed above in regard to claim 57. Claim 18 recites the 5' AAV2 terminal repeat has the nucleotide sequence set forth as SEQ ID NO:6 (which is the same as SEQ ID NO:6) and/or wherein the hGRK promoter has the nucleotide sequence set forth as SEQ ID NO:4 (which is the same as SEQ ID NO:4) and/or wherein the SV40 polyadenylation sequence has the nucleotide sequence set forth as SEQ ID NO:8 (which is the same as SEQ ID NO:8) and/or wherein the 3' AAV2 terminal repeat has the nucleotide sequence set forth as SEQ ID NO:7 (which is the same as SEQ ID NO:7). Instant claim 59 is met by claim 19 of U.S. Patent No. 11,345,930. Claim 19 recites a method as disclosed above in regard to claim 58. Claim 19 recites the rAAV vector comprises (i) a capsid comprising a capsid protein comprising or consisting of the sequence of SEQ ID NO:9 (which is the same as SEQ ID NO:9 of the present application) and (ii) a nucleic acid comprising or consisting of the nucleotide sequence of SEQ ID NO:5 (which is the same as SEQ ID NO:5 of the present application). Instant claim 60 is met by claim 20 of U.S. Patent No. 11,345,930. Claim 20 recites a method as disclosed above in regard to claim 59. Claim 20 recites the pharmaceutical composition is administered to the subject by periocular, intravitreal, suprachoroidal or subretinal injection. Instant claim 61 is met by claim 21 of U.S. Patent No. 11,345,930. Claim 21 recites a method as disclosed above in regard to claim 60. Claim 21 recites the vector is administered to the subject at a dosage from about 1010 vector genomes (vg)/eye to about 1013 vg/eye. Instant claim 62 is met by claim 22 of U.S. Patent No. 11,345,930. Claim 22 recites a method as disclosed above in regard to claim 61. Claim 22 recites the vector is administered to the subject at a dosage from about 1 x 1011 vg/eye to about 5 x 1012 vg/eye. Instant claim 63 is met by claim 23 of U.S. Patent No. 11,345,930. Claim 23 recites a method as disclosed above in regard to claim 62. Claim 23 recites the vector is administered to the subject at a dosage from about 3 x 1011 vg/eye or at a dosage of about 1 x 1012 vg/eye. Instant claim 64 is made obvious by claim 24 of U.S. Patent No. 11,345,930. Claim 24 recites the pharmaceutical composition and at least one pharmaceutically acceptable excipient. Claim 24 recites the rAAV vector comprising a heterologous nucleic acid comprising the expression cassette comprising a nucleic acid as described above in regard to claim 42, wherein the nucleotide sequence set forth as SEQ ID NO: 1 or the nucleotide sequence at least 95% identical thereto is operably linked to an expression control sequence. Instant claim 65 is met by claim 24 of U.S. Patent No. 11,345,930. Claim 24 recites the pharmaceutical composition and at least one pharmaceutically acceptable excipient. Claim 24 recites an rAAV vector as disclosed above in regard to claim 52. Claim 24 recites the rAAV vector comprises a nucleic acid comprising from 5' to 3': (a) an AAV2 terminal repeat (b) an hGRK promoter (c) codon optimized RPGRorf15 gene of SEQ ID NO:1 (which is the same as SEQ ID NO:1 of the present application) and (d) an AAV2 terminal repeat. Instant claim 66 is met by claim 25 of U.S. Patent No. 11,345,930. Claim 25 recites a pharmaceutical composition as disclosed above in regard to claim 64. Claim 25 recites the pharmaceutical composition comprises between 109 vg and 1014 vg of the rAAV or comprises between 1010 vg and 1013 vg of the rAAV, or comprises about 3 x 1011 vg or about 1 x 1012 vg of the rAAV. Conclusion Any inquiry concerning this communication or earlier communications from the examiner should be directed to Catherine L McCormick whose telephone number is (703)756-5659. The examiner can normally be reached Monday-Friday, 8:30 am-5:30 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, Tracy Vivlemore can be reached at (571) 272-2914. 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. /C.L.M./Examiner, Art Unit 1638 /Anna Skibinsky/ Primary Examiner, AU 1635
Read full office action

Prosecution Timeline

Feb 22, 2023
Application Filed
Oct 09, 2025
Non-Final Rejection — §DP (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
52%
Grant Probability
68%
With Interview (+16.7%)
3y 8m
Median Time to Grant
Low
PTA Risk
Based on 29 resolved cases by this examiner. Grant probability derived from career allow rate.

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