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
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
This action is in response to the papers filed on December 19, 2025. Claims 1-11 and 13-15 are currently amended.
Election/Restrictions
Claim 17-20 were previously withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking
claim. Election was made without traverse in the reply filed on May 15, 2025.
Therefore, claims 1-16 are currently under examination.
Priority
The present application, filed on September 20, 2022, is a CON of PCT/EP2021/058798, filed April 02, 2021. Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). Receipt is acknowledged of priority document EP20167817.4, filed June 2, 2023.
Thus, the earliest possible priority for the instant application is April 02, 2020.
Withdrawn- Specification Objection
In view of the concurrent submission of a substitute specification, removing hyperlinks the objections to the specification have been withdrawn.
Maintained- Title Objection
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed.
Withdrawn- Claim objections
In view of Applicants’ amendment to claim 4, 8, 9, 11, correcting the indicated informalities, the objections to improper form are moot and have been withdrawn.
In view of Applicants’ amendment reciting the sequence identifier SEQ ID NO: 32, in claim 4, the objections to improper form are moot and have been withdrawn.
Upon further consideration, the objection to claim 5, 9,10, and 12 has been withdrawn.
Maintained- Claim objections
Claims 8 remains objected to because it recites the sequences of Rep 40, Rep 52, Rep 58, Rep 68, and Rep 78 proteins, along with varying percent identities ranging from 60% to 90%. Applicant asserts that “in claims 4, 5, 8-10 and 12 the sequence identifiers have been added,” but no sequences identifiers are found here. The claim recites Rep sequences in terms of sequence homology or percent identity, but does not identify any reference sequence or defined sequence boundaries.
Where the description or claims of a patent application discuss a sequence that is set forth in the "Sequence Listing," in accordance with paragraph (c) of this section, reference must be made to the sequence by use of the sequence identifier (§ 1.823(a)(5) ), preceded by "SEQ ID NO:" or the like, in the text of the description or claims, even if the sequence is also embedded in the text of the description or claims of the patent application.
New Claim Objections
Claims 4-5 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.
Withdrawn- Claim Rejections - 35 USC § 112(b)
In view of Applicants’ amendment to claim 3, amending the claim to be dependent upon claim 3, the rejection of claim 3 under 35 U.S.C. 112(b) has been withdrawn.
In view of Applicants’ amendment to claim 4, 7, and 13-15 correcting antecedent basis, the rejection of claims 4-5, 7, and 13-15 under 35 U.S.C. 112(b) has been withdrawn.
Upon further consideration, the rejection of claims 6 under 35 U.S.C. 112(b) has been withdrawn.
In view of Applicants’ amendment to claim 9, no longer reciting “the codon usage” and clarifying the metes and bounds of the claim, the rejection of claim 9 under 35 U.S.C. 112(b) has been withdrawn.
In view of Applicants’ amendment to claim 10, no longer reciting exemplary language, the rejection of claim 10 under 35 U.S.C. 112(b) has been withdrawn.
Maintained- Claim Rejections - 35 USC § 112(b)
Claim 8 remains rendered vague and indefinite in the recitations of “a common amino acid sequence that is at least 90% identical” and less than 60% sequence identity with the nucleotide sequence encoding the common the amino acid sequence. The ordinary artisan would be unable to reasonably determine the metes and bounds of the claim because it is unclear what the start/stop positions are, if this is referring to a contiguous region, or what the common amino acid is identical to. The person of ordinary skill in the art would not be able to determine which exact coding region is intended to be compared.
Claim 9 is rejected for being dependent from the rejected claim 8 and for failing to further clarify the basis of the rejection.
Response to Applicants’ arguments as they apply to the rejection of Claims 8-9 under 35 USC § 112(b) and claims
Applicants’ arguments filed December 19, 2025, have been fully considered but they are
not persuasive. At page 10 of the remarks filed on December 19, 2025, Applicants’ essentially argue one skilled in the art would be able to determine what portions of the amino acid and nucleotide sequences could be modified while still maintaining positions, regions, and individual amino acids associated with required functions of the Rep proteins. Additionally, Applicant’s argue a person of ordinary skill in the art would be able to determine which exact coding region is intended to be compared, since the specification defines sequence identity.
This argument is not persuasive because the specification describes general principles of sequence identity and functional conservation, the claims do not identify any specific reference sequence, defined region, or clearly bounded coding sequence against which the recited sequence percent identity is to be measured. It is still unclear what constitutes the “common amino acid sequence” or which specific portion of the Rep protein is being used as the basis for comparison. The claims do not specify whether the percent identity applies to a full-length sequence, a contiguous fragment, or a non-contiguous set of residues, nor do they define alignment parameters or endpoints for comparison.
Withdrawn- Double Patenting
Applicant’s arguments, see pg. 11, filed December 19, 2025, with respect to the claim 1 amendment identifying the first promoter as a delayed early promoter have been fully considered and are persuasive. The nonstatutory double patenting rejection of claims 1-16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 11,667,931 B2, in view of the prior art teachings of Zolotukhin et al. (US 8,679,837 B2, patented March 25, 2014), Bakker et al. (US 8,642,314 B2, patented February 4, 2014), and Wilhelmus et al. (US 8,512,981 B2; patented August 20, 2013) have been withdrawn. Applicants’ arguments are moot in view of the withdrawn rejection. A response to Applicant’s arguments pertinent to a new or remaining rejection can be found below.
New- 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.
This is a new rejection necessitated by Applicants’ amendments to the claims in the response filed on December 19, 2025.
Claims 1-3, 6-7, and 10-16 are newly rejected on the grounds of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 11,667,931 B2. Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1, 9, 11, and 12 anticipates an insect cell comprising a Rep78 or a Rep68 coding sequence operably linked to expression control sequences and Rep52 or a Rep40 coding sequence operably linked to expression control sequences for expression in an insect cell, as well as transcriptional transregulators, such as the E1 promoter. The ordinary artisan would have recognized expression control sequences include conventional genetic elements, such as enhancers and protomers.
Furthermore, the ordinary artisan would have found it obvious to incorporate the limitations of a delayed early baculoviral promoter and the dependent claims, further in view of the prior art teachings of Lin et al. (J Biotechnol. 2013 May 10;165(1):11-7. Epub 2013 Feb 28.), Zolotukhin et al. (US 8,679,837 B2, patented March 25, 2014), Bakker et al. (US 8,642,314 B2, patented February 4, 2014), and Wilhelmus et al. (US 8,512,981 B2; patented August 20, 2013).
The claimed invention differs from the ‘931 patent primarily in reciting the use of a delayed early promoter, such as the species of 39K promoter. However, Lin teaches that delayed early promoters can be used in engineered insect cells to achieve inducible expression upon baculoviral infection (Abstract; pg. 16, Section 4). It would have been obvious to one of ordinary skill in the art to have simply substituted a delayed early baculoviral promoter, such as the 39k promoter, as a predictable alternative to immediate early or late promoters for use as expression control sequence in the insect cell systems of the ‘931 patent in order to achieve regulated and inducible expression of transgenes, including Rep proteins, with a reasonable expectation of success.
Regarding claims 2-3, ‘931 discloses where the nucleic acid construct comprises the promoter selected from the group consisting of baculoviral immediate-early promoters, such as the E1 promoter. Furthermore, Zolotukin specifically teaches the utilization of the immediate-early (IE-1) transcriptional transregulator for novel, simple and efficient system of rAAV production in insect cells (Fig. 5-6; column 1, lines 37-50). Additionally, Bakker discloses parallel constructs for the same purposes, specifically teaching the utility of baculoviral enhancer elements selected from the group consisting of hr1, hr2, hr3, hr4 and hr5 (column 10 to column 11, bridging para.). Likewise, Wilhelmus additionally teaches dual Rep expression cassettes, Rep 78 and Rep 52, under independent insect promoter with improved stability (claim 1; column 2, para. 3). Given that such hr elements were known to enhance IE-1 responsive promoters, it would have been obvious to include an hr element to achieve the enhancer-dependency recited. Regarding the limitation of wherein the baculovirus is Autographa californica multicapsid nucleopolyhedrovirus, the species of baculovirus was additionally taught by Zolotukin (column 4, lines 35-59). Other suitable baculoviruses were also taught by Wilhelmus (column 16, lines 45-48; column 19, lines 53-53-56).
It would have been obvious for one of ordinary skill to combine these teachings to provide an insect cell containing enhancer-responsive, dual Rep expression cassettes under baculoviral promoter control. The ordinary artisan would have been motivated to make such a combination to achieve balanced and inducible Rep expression for improved rAAV production efficiency and stability, as each reference teaches complementary features directed towards the same production goals, such as improving coordinated Rep expression and AAV productivity.
Regarding claims 6-7 and 10-16, ‘931 discloses insect cells employing baculoviral vectors (claim 10), along with AAV capsid proteins, a species of parvovirus, as well as inverted terminal repeat sequences from an AAV, or ITRs (claims 1, 8, and 12-13). Lin teaches the utility of the 39K delayed early promoter in parallel systems (Abstract). Zolotukhin teaches use of IE-1 to induce or enhance expression from baculoviral promoters, including polH (Fig. 1; column 4, par. 1-2; Example 2, 3 and 5), while Bakker describes baculoviral hr-type enhancers, hr1 to hr5, that potentiate IE-1-dependent transcription for infection-induced production of recombinant paroviral particles (claims 1, 8, and 9). Bakker (column 16, para. 3; column 17, para. 2-3) and Wilhelmuss (column 13 through column 14, para. 3) also discloses where the cap coding sequences are selected from AAV5. Additionally, Wilhelmus teaches independent Rep 78/68 and Rep 52/40 expression units under insect promoters with codon and start-codon modifications to balance protein levels, and further discloses integration of AAV expression cassettes into insect-cell genomes for stable production (claims 5 and 11; column 5, para. 1-2; column 7, para. 1-3; column 11, last para.). Hence, the prior art taught the claimed features of enhancer-dependent inducible Rep expression, codon-usage modulation or adoption index, integrated REP/CAP/transgene cassettes, and infection-induced production of recombinant paroviral particles.
Regarding limitations such as the first and second promoter directions of transcription, the presence of an enhancer element between the promoters, or other relative placements of the recited components, such selection in cells is deemed merely a matter of judicious selection that is well within the purview of the skilled artisan, in view of Zolotukhin (column 4, para. 1 through column 5, para. 1; Fig. 7), Bakker (column 4, para. 4; column 15, para. 3; column 22, para. 3), and Wilhelmus (column 8 through column 9, bridging para.). Before the effective filing date of the instant application, the ordinary artisan would have found it obvious to combine these teachings to achieve coordinated, inducible, and stable Rep and Cap expression in insect cells for improved rAAV productivity, further in view of the teachings of Lin, Zolotukhin, Bakker, and Wilhelmus, with a reasonable expectation of success since each references addresses complementary and predictable aspects of baculoviral-regulated AAV vector manufacturing.
Response to Applicants’ arguments as they apply to the rejection of Claims 1-3, 6-7, and 10-16 on the ground of nonstatutory obviousness-type double patenting
Applicant's arguments filed December 19, 2025, have been fully considered but they are not persuasive.
At page 11 of the remarks filed on December 19, 2025, Applicant’s arguments with respect to claims 1-3, 6-7, and 11-15 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument. In the instant case, the delayed early promoter, specifically the 39K promoter, was well established for its utility in providing temporally regulated, baculovirus-inducible expression of transgenes in insect cells, thereby representing a known and practical alternative expression control element for achieving controlled protein expression, in view of the teachings of Li.
Conclusion
Claims 1-3 and 6-16 are rejected.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOEL D LEVIN whose telephone number is (571)270-0616. The examiner be reached 8:00 am to 5:00 pm, Monday through Friday.
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, Christopher Babic can be reached at (571) 272-8507. 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.
/J.D.L./Examiner, Art Unit 1633
/FEREYDOUN G SAJJADI/Supervisory Patent Examiner, Art Unit 1699
Prosecution Insights