Office Action Predictor
Application No. 18/048,716

METHODS AND COMPOSITIONS FOR DELIVERY OF AGENTS ACROSS THE BLOOD-BRAIN BARRIER

Non-Final OA §DP
Filed
Oct 21, 2022
Examiner
LI, BAO Q
Art Unit
1671
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
The Brigham And Women'S Hospital, INC.
OA Round
3 (Non-Final)
76%
Grant Probability
Favorable
3-4
OA Rounds
2y 11m
To Grant
96%
With Interview

Examiner Intelligence

76%
Career Allow Rate
675 granted / 890 resolved
Without
With
+20.7%
Interview Lift
avg trend
2y 11m
Avg Prosecution
30 pending
920
Total Applications
career history

Statute-Specific Performance

§101
4.2%
-35.8% vs TC avg
§103
19.3%
-20.7% vs TC avg
§102
27.7%
-12.3% vs TC avg
§112
28.0%
-12.0% vs TC avg
Black line = Tech Center average estimate • Based on career data

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 . RCE A request for continued examination (RCE) under 37 CFR 1.114 (d) filed on June 30, 2025 is acceptable and a RCE has been established. An action on the RCE follows. Summary Applicant's response and amendment filed on 1June 30, 2025 have been acknowledged. The status of claim Claims 1-30 were canceled. Claims 31-57 are pending. Claims 41, 52 and 57 previously withdrawn from consideration are rejoined as they are directed to generic claims under the examination. Claims 31-57 with elected species of c). Hippocampus, B), Alzheimer’s diseases and i). Neurons delivery consideration. 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 claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). 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 31-42 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 and 14 of U.S. Patent No. 11,981,705 as evidenced by Kniesel et al. (Cell Mol. Neurobiology. 2000, Feb. 20 (1), pp. 57-76), Banks (Peptides. 2015 October ; 72: 16–19. doi:10.1016/j.peptides.2015.03.010) and Tanaka et al. Sci Rep 2019 Apr 8;9:5769). In the instant case, upon further considering the pending claims, the conflict claims still comprise overlapping scopes, while the issued reference claims read on a specific therapeutic transgene as an antibody or its fragment thereof, which is delivered into brain for treatment brain of a subject who needs treatment of glioblastoma. The antibody or its fragment thereof are all belonged to be a therapeutic agent coded by the transgene in addition to the VVP capsid protein inserted with a peptide including the TVSALFK (SEQ ID NO: 8) cited in the current rejected claims. Moreover, they are also delivered into brain , wherein the delivery into brain is inherently pass through blood-brain barrier (BBB), wherein the endothelial cells of the BBB comprise tight junctions and certain permeability between the endothelial cells of the brain microvasculature as evidenced by Kniesel et al. All of other organs cited in the claims are all comprised inherently. Banks teaches that BBB permeability to peptides seemed to occur for many peptides. Taken together, prior to the current Application was originally filed, it was well known that blood -brain barrier (BBB) contains tight junctions and it is permeable to many short peptide. provide evidence for Tyr-Pro accumulation in the hippocampus, hypothalamus, striatum, cerebral cortex, and cerebellum of mouse brain. Tanaka et al. also provide evidence for Tyr-Pro accumulation in the hippocampus, hypothalamus, striatum, cerebral cortex, and cerebellum of mouse brain (See Abstract and Fig. 5-6). For the same notion as described supra in paragraphs 15, unless any specific measurement of the particular locations of the brains are measured , those generic intended functions or activities of the transgene as it is claimed passing through the tight junction and permeability to the BBB is inherently met. An obviousness-type double-patenting rejection is appropriate where the conflict claims are not identical but an examined application claim is not patentably distinct from the reference claim(s) because the examined claim(s) is either anticipated by or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 14U F.3d 1428, 46 USPQZd 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQZd 2010 (Fed. either anticipated by, 1993); In re Longi, F.2d 887, 225 US/Q 645 (Fed. Cir. 1985). Although the conflicting claims are not identical, they are not patentably distinct from each other. Because the issued reference claims while with specific transgene of antibody in addition to other obvious or inherently same limitations, the issued reference claims also meet all limitations of the rejection claims obviously or inherently. The rejection is resumed. Claims 31-50 and 51-57 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 7 and 9-11of U.S. Patent No.12, 398, 181B2 in light of the teaching by Kniesel et al. (Cell Mol. Neurobiology. 2000, Feb. 20 (1), pp. 57-76), Banks (Peptides. 2015 October ; 72: 16–19, doi:10.1016/j.peptides.2015.03.010) and Tanaka et al. (Sci Rep 2019 Apr 8;9:5769. doi: 10.1038/s41598-019-42099-9). Although the claims at issue are not identical, they are not patentably distinct from each other because The issued reference claims are and rejected claims are obviously read into each other with overlapping scopes. For instance, the rejected claims are directed to A method of delivering a transgene to a subject, the method comprising administering to the subject an adeno-associated virus (AAV) vector comprising (i) a transgene, and (ii) an AAV capsid comprising a peptide insert of up to 21 amino acids, wherein the peptide insert comprises 5-7 contiguous amino acids of TVSALFK (SEQ ID NO: 8), wherein the transgene is a therapeutic related agent and the 5-7 contiguous amino acids of TVSALFK (SEQ ID NO: 8) is enhanced relative to an AAV vector comprising an AAV capsid without the peptide insert and the transgene. The reference claims are directed to an AAV capsid protein comprising a targeting sequence that comprises TVSALFK (SEQ ID NO:8); TVSALK (SEQ ID NO:4); KLASVT (SEQ ID NO:83); or KFLASVT (SEQ ID NO:84), wherein the targeting sequence is inserted in a position corresponding to amino acids 588 and 589 of SEQ ID NO:85, wherein the AAV comprising a capsid that further comprising a transgene, wherein the transgene is a therapeutic transgene or a non-coding RNA, wherein the transgene encodes an anti-cancer agent. Although the rejected claims are directed to a method for treating a cancer with the AAV comprising the peptide TVSALFK (SEQ ID NO:8) and a transgene , the reference claims are directed to AAV used by the claimed method under the rejection. For the same notion as described supra in paragraphs 15, unless any specific measurement of the particular locations of the brains are measured , those generic intended functions or activities of the transgene as it is claimed passing through the tight junction and permeability to the BBB is inherently met. Therefore, they are obvious rather than distinct for any person ordinarily skilled in the art. An obviousness-type double-patenting rejection is appropriate where the conflict claims are not identical but an examined application claim is not patentably distinct from the reference claim(s) because the examined claim(s) is either anticipated by or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 14U F.3d 1428, 46 USPQZd 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQZd 2010 (Fed. either anticipated by, 1993); In re Longi, F.2d 887, 225 US/Q 645 (Fed. Cir. 1985). Although the conflicting claims are not identical, they are not patentably distinct from each other. The rejection of Claims 31-33, 43, 44, 54 over claims 9, 18, 32, 33 are still rejected over the copending Application No. 17,258,846 (reference application) has been removed because the TD has been filed and accepted. The argument of rejection of Claims 31-33, 43, 44, 54 on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 6-9 and 11 of copending Application No. 18,633, 827 (reference application) has been considered. Which is persuasive to overcome the rejection. The argument of rejection of Claims 31-33, 43, 44, 54 on the ground of nonstatutory double patenting as being unpatentable over claims 9-14 of copending Application No. 17,845,225 (reference application) has been considered. Which is persuasive to overcome the rejection. Conclusion No claims are allowed . However, Applicants are encouraged to amend claims and provide some evidence indicating the particular intended functions and activities in certain generically mentioned disease or cancer are specially observed in a condition(s) presented and found in the Applications rather than a generically inherited while the specially patients with the particular disease are selected and treated as an active step(s). Otherwise the Terminal Disclaimers are still required to overcome the rejection. Any inquiry concerning this communication or earlier communications from the examiner should be directed to BAO Q LI whose telephone number is (571)272-0904. The examiner can normally be reached M-F 8 am to 8 pm EST. 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, Janet Andres can be reached at 571-272-0867. 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. BAO Q. LI Examiner Art Unit 1671 /BAO Q LI/ Primary Examiner, Art Unit 1671
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Prosecution Timeline

Oct 21, 2022
Application Filed
Apr 20, 2023
Response after Non-Final Action
May 30, 2024
Non-Final Rejection — §DP
Nov 06, 2024
Response Filed
Dec 27, 2024
Final Rejection — §DP
Jun 17, 2025
Examiner Interview Summary
Jun 17, 2025
Applicant Interview (Telephonic)
Jun 30, 2025
Request for Continued Examination
Jul 07, 2025
Response after Non-Final Action
Sep 23, 2025
Non-Final Rejection — §DP
Mar 24, 2026
Response Filed

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Prosecution Projections

3-4
Expected OA Rounds
76%
Grant Probability
96%
With Interview (+20.7%)
2y 11m
Median Time to Grant
High
PTA Risk
Based on 890 resolved cases by this examiner