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 .
Application Status
Applicant’s amendment field September 22, 2026, amending claims 1-3, and canceling claim 38 is acknowledged. Claims 1-4, 7, 33, 39-40, 42, 44-45 and 49-51 are pending. Claim 33 remains withdrawn as being drawn to a nonelected species, there being no allowable generic or linking claim. Claims 1-4, 7, 39-40, 42, 44-45, and 49-51 are under examination. Additionally, the elected species of a "polypeptide other than an antibody" as the molecular class of the SAMHD1 inhibitor is under examination. See Remarks filed June 21, 2024, page 10.
The effective filing date of the pending claims remains March 5, 2020. R2Tg retrotransposase polypeptides comprising an RT domain and an endonuclease domain are incorporated by reference in the 62/985750 provisional application.
Withdrawn Rejections
The amendment to claims 1-4 and cancelation of claim 38 overcome the §112(b) and/or §112(d) rejections. The amendments to claims 1-3 overcome the §112(a) in the previous office action, but are now rejected for having new matter. Applicant’s amendments and arguments have been thoroughly reviewed, but are not persuasive to place the claims in condition for allowance for the reasons that follow.
Claim Rejections - 35 USC § 112(a)
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 1-4, 7, 39-40, 42, 44-45, and 49-51 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 possession of the claimed invention. This is a new NEW MATTER rejection, necessitated by amendment.
MPEP 2163.II.A.3.(b) states, “when filing an amendment an applicant should show support in the original disclosure for new or amended claims” and “[i]f the originally filed disclosure does not provide support for each claim limitation, or if an element which applicant describes as essential or critical is not claimed, a new or amended claim must be rejected under 35 U.S.C. 112a, as lacking adequate written description". According to MPEP § 2163.I.B, "While there is no in haec verba requirement, newly added claim limitations must be supported in the specification through express, implicit, or inherent disclosure" and "The fundamental factual inquiry is whether the specification conveys with reasonable clarity to those skilled in the art that, as of the filing date sought, applicant was in possession of the invention as now claimed. See, e.g., Vas-Cath, Inc., 935 F.2d at 1563-64, 19 USPQ2d at 1117".
In the instantly rejected claims, the new limitation of providing an R2Tg retrotransposase RT and endonuclease domains as an mRNA to a cell in combination with using an SAMHD1 inhibitor in claims 1-3 appears to represent new matter. No specific basis for this limitation was identified in the specification, nor did a review of the specification by the examiner find any basis for the limitation.
R2Tg domains are recited in the Specification five times. The first is on page 121 where the RT domain is fused to a Cas9 domain, which is not the claimed method. The 2nd, 3rd, 4th and 5th instances are in Example 8 on page 183. Here, Applicant describes a prophetic example where an R2Tg “driver” is provided to cells as a plasmid that encodes R2Tg, which is assumed to be a wild type R2Tg retrotransposon having the ORF for the R2Tg enzyme with RT and endonuclease functions. This example does not 1) provide R2Tg to cells as an RNA or 2) provide the cells with an SAMHD1 inhibitor.
Example 4 on pages 179-180 is a prophetic example that describes using the SAMHD1 inhibitor Vpx to improve a generic Gene Writer function. In this example a Vpx is provided with an mRNA encoding a Gene Writer polypeptide “targeting AAVS1”. As an R2 retrotransposon, R2Tg can only integrate DNA at the rDNA locus. See e.g., Kojima et al., PLoS ONE (2016), 11(9): e0163496. Applicant does not disclose how to engineer an R2Tg endonuclease/RT protein to target any other locus. Therefore, the skilled artisan would not have concluded that the “Gene Writer” taught in example 4 could be an R2 RT-endonuclease like R2Tg.
There are no other disclosures in the 189-page disclosure that discuses R2 retrotransposons generically or R2Tg specifically. Since no basis has been identified, the claims are rejected as incorporating new matter.
Response to Arguments
Applicant argues that support for the R2Tg can be found without incorporation by reference, specifically in Example 8, and by that disclosure, the skilled artisan would recognize that Applicant had possession of the full scope of claims 1-3 (Remarks, page 9). This argument has been fully considered, but is not persuasive as it applies to the new §112(a) rejection. As explained above Example 8 is not sufficient support for the combination of 1) R2Tg, 2) provided as an mRNA, and 3) administered with an SAMDH1 inhibitor.
Conclusion
No claims are allowable.
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 CATHERINE KONOPKA whose telephone number is (571)272-0330. The examiner can normally be reached Mon - Fri 7- 4.
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/CATHERINE KONOPKA/Primary Examiner, Art Unit 1635
