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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on September 09, 2026 has been entered.
Status of the Claims:
Claims 1-26, 31-35 and 37 are cancelled. Claims 27-30, 36, 38-44, 48 and 50 are pending and are being examined. New claim 49 is withdrawn as being directed to unelected species. Claims 45-47 and 49 are withdrawn as being directed to unelected group.
Claim Interpretation
Optional embodiments are not required by the claim and are not considered for patentability as they are not required elements. For example, section (c) of claim 1 requires an optional polynucleotide linker is not being considered for patentability.
MAINTAINED REJECTION
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.
Claim 27-28, 31-35 and 44 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18, and 20-21 of copending Application No. 18/258,039 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding claims 27-28: Claim 20 of ‘039 application disclosed a nucleic acid encoding a first DNA binding protein capable of binding and cleaving a nucleic acid construct and a second nucleic acid construct comprising a transposase is a modified hyperactive PiggyBac, comprising one or more amino acid mutations as compared to hyperactive PiggyBac of SEQ ID NO: 9. As such the disclosure of claim 1 of ‘039 application reads on the subject matter of claim 27.
Regarding claim 31-35: Claim 8 of ‘039 application disclosed mutations at R275, R277, R347, R372, K375, R376, E377, and/or E380.
Regarding claim 44: Claim 21 of 039 Application recited “method for site specific integration of an exogenous nucleic acid sequence into the genome of a cell, the method comprising delivering to the cell the composition according to claim 1, a guide RNA, and the exogenous nucleic acid”. As such it would have been obvious for a person to arrive at the claimed method of site specific integration using the nucleic acid of claim 27 and an exogenous nucleic acid in view of the steps taught by ‘039 application.
Response to Arguments: Applicants argued that the present application has an effective filing date of June 11, 2020, which is earlier than the effective filing date of December 16, 2021, for the 18/258,039 Application. Consequently, pursuant to M.P.E.P. § 1490(VI)(D) this rejection should be withdrawn.
It is submitted that according to MPEP 804(I)(B)(1)(b)(i) and MPEP 1490(VI)(D)(2)(a), a provisional nonstatutory double patenting rejection is only withdrawn when it is the only rejection remaining in an application having the earliest effective U.S. filing date (taking into account any benefit under 35 U.S.C. 120, 121, 365(c), or 386(c) ) with respect to the conflicting claims); at which point the "provisional" nonstatutory double patenting rejection in the other (later filed) application(s) will be converted into a nonstatutory double patenting rejection when the application with the earliest U.S. effective filing date issues as a patent.
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NEW REJECTIONS
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 27-30, 36, 38-44, 48 and 50 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims require a “second DNA binding protein, and the optional linker between the first DNA binding protein and the second DNA binding protein;
wherein the fusion protein enables insertion of the exogenous nucleic acid into a specific site of the genome; and wherein the one or more amino acid mutations of the modified transposase are selected from: R245A, R275A, R277A, R275A and R277A, G325A, N347A, N347S, S351E, S351P, S351A, R372A, K375A, R388A, D450N, W465A, T560A, S564P, S573A, M589V, S592G, or F594L corresponding to the amino acid sequence SEQ ID NO: 9.”
The specification does not provide adequate written description support for full scope of the claimed modified transposase encompassing each of the recited individual mutations and mutation combinations as a transposase that enables insertion of an exogenous nucleic acid into the genome. Although the specification identifies various PiggyBac mutations, the functional data described in the specification does not demonstrate that each recited mutation, when present as the claimed modified transposase, is integration competent.
This deficiency is particularly apparent for R245A, R275A/R277A, S351E, R372A/K375A, and R388A among others. These PiggyBac mutations were previously characterized as having no or very low or substantially reduced integration activity. (See Li E2280, col. 2, para 1). While it is noted that Table 3 provides at least some structural disclosure of the claimed transposase, the claim requires that the modified transposases enable insertion of the exogenous nucleic acid into a genome. As such mere listing of the mutations without establishing that those variants possess the claimed integration function does not necessarily demonstrate the claimed functional species. As such it is submitted that the specification may support some species within the genus, but not necessarily the entire genus recited in claim 27. For example, paragraph [00464] reports that hCas9_PB D450N and hCas9_PB R372A/K375A/D450N exhibited higher targeted transposition relative to random transposition than hCas9_PB WT. Paragraphs [00490]-[00491] further identify particular “Unilarge” mutant combinations as having increased targeted insertion relative to overall integration, including Unilarge-B (R245A/D450N), Unilarge-C (R245A/G325A/D450N/S573P), and Unilarge-D (R245A/G325A/S573P). The specification states that these combinations were identified and validated as capable of site-directed insertion. It is noted that although [0488] indicated SEQ ID NOs 120-129 as mutated PB sequences, however, for example FIG. 26 provided functional evidence for only particular species/combinations. Therefore, listing mutations or identifying them from a screening library does not constitute every individual mutation alternative claimed as having insertion function.
The specification therefore does not reasonably convey possession of the claimed genus of modified transposases having the recited insertion function. Claims 28-30, 36, 38-44, 48 and 50 are rejected for their dependency on the rejected claim.
WITHDRAWN REJECTIONS
Claim Rejections - 35 USC § 103
RE: Rejection of Claims 27-28, 30, 38, 39, 40 and 44 under 35 U.S.C. 103 as being unpatentable over Shrock et al (WO2018175872A1; Hereinafter "Shrock;" Published Sep. 27, 2018; See PTO-892 of 10/07/2025) in view of Li et al (Proc Natl Acad Sci U S A. 2013 Jun 18; Hereinafter “Li;” See PTO-892 of 10/07/2025).
RE: Rejection of Claim 29 under 35 U.S.C. 103 as being unpatentable over Shrock et al (WO2018175872A1; Hereinafter "Shrock;" Published Sep. 27, 2018; See PTO-892 of 10/07/2025) in view of Li et al (Proc Natl Acad Sci U S A. 2013 Jun 18; Hereinafter “Li;” See PTO-892 of 10/07/2025) and further in view of Chen et al (Adv Drug Deliv Rev. 2013 Oct; hereinafter “Chen”; See PTO-892 of 10/07/2025).
RE: Rejection of Claim 36 under 35 U.S.C. 103 as being unpatentable over Shrock et al (WO2018175872A1; Hereinafter "Shrock;" Published Sep. 27, 2018; See PTO-892 of 10/07/2025) in view of Li et al (Proc Natl Acad Sci U S A. 2013 Jun 18; Hereinafter “Li;” See PTO-892 of 10/07/2025) and further in view of Wu et al (US20180320196A1; Published Nov 8, 2018; Hereinafter “Wu;” See IDS 5/1/2026).
RE: Rejection of Claims 41-43 under 35 U.S.C. 103 as being unpatentable over Shrock et al (WO2018175872A1; Hereinafter "Shrock;" Published Sep. 27, 2018; See PTO-892 of 10/07/2025) in view of Li et al (Proc Natl Acad Sci U S A. 2013 Jun 18; Hereinafter “Li;” See PTO-892 of 10/07/2025) and further in view of Hart et al (G3 (Bethesda). 2017 Aug 7; Hereinafter "Hart;" See PTO-892 of 10/07/2025).
RE: Rejection of Claim 48 under 35 U.S.C. 103 as being unpatentable over Shrock et al (WO2018175872A1; Hereinafter "Shrock;" Published Sep. 27, 2018; See PTO-892 of 10/07/2025) in view of Li et al (Proc Natl Acad Sci U S A. 2013 Jun 18; Hereinafter “Li;” See PTO-892 of 10/07/2025) and further in view of Wu et al (US20180320196A1; Published Nov 8, 2018; Hereinafter “Wu;” See IDS 5/1/2026).
The rejection of the claims in view of the cited references are withdrawn in view of 112(a) rejections presented here.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAGAMYA VIJAYARAGHAVAN whose telephone number is (703)756-5934. The examiner can normally be reached 9:00a-5:00p.
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/JAGAMYA NMN VIJAYARAGHAVAN/Examiner, Art Unit 1633
/EVELYN Y PYLA/Primary Examiner, Art Unit 1633
