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 .
Status of the Claims
Applicant’s submission filed 21 May 2026 has been entered. Claims 8-10, 14, and 25-30 are pending. Claim 8 has been amended. Therefore, prosecution on the merits continues for claims 8-10, 14, and 25-30 as being drawn to the elected invention. All arguments have been fully considered with the status of each prior ground of rejection set forth below.
Status of Prior Rejections/Response to Arguments
RE: Rejection of claims 8-10, 14, and 25-30 under 35 USC 103 over Finer et al as evidenced by Vergunst et al, in view of Sardesai et al and Kim
Applicant has amendment independent claim 8 to require the Agrobacterium effector protein to comprise a DNA binding domain, wherein the DNA binding domain is capable of binding to a T-DNA sequence comprising a DNA homology repair template that comprises an edit for incorporation into a target sequence. With this amendment, Applicant's arguments filed 21 May 2026 have been fully considered but they are not persuasive.
Applicant has traversed the rejection, asserting in Pages 4-6 of the Remarks filed 21 May 2026 that Finer et al fail to provide guidance, direction, or enablement for a fusion protein as claimed, especially one comprising a T4SS secretion signal and a DNA binding domain that can bind a T-DNA sequence. In response, the Examiner respectfully submits that a reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, even nonpreferred embodiments. See MPEP § 2123: Merck & Co. v. Biocraft Labs., Inc. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989); Upsher-Smith Labs. v. Pamlab, LLC, 412 F.3d 1319, 1323, 75 USPQ2d 1213, 1215 (Fed. Cir. 2005). In the instant case, Finer et al do disclose a fusion protein product comprising an Agrobacterium virulence protein and a CRISPR-Cas effector protein for the delivery of T-DNA into a target gene. See, for example, Paragraphs [0047], [0053], [0082]-[0087], [0093] of Finer et al. With that, in regards to the teaching of a T4SS secretion signal and DNA binding domain, Sardesai et al disclose an Agrobacterium VirD2 protein having a T4SS secretion signal and DNA binding domain, as the VirD2 protein covalently binds the T-DNA sequence. See, for example, Paragraphs [0076] and [0079] of Sardesai et al. Therefore, the ordinary artisan would have reasonably arrived at the fusion protein of the instant claim comprising, in part, an Agrobacterium effector protein having a T4SS secretion signal and DNA binding domain that is capable of binding to a T-DNA sequence.
Applicant has further traversed the rejection, asserting in Pages 6-8 of the Remarks filed 21 May 2026 that the disclosure of Vergunst et al teach that the transport of heterologous sequences via Agrobacterium effector protein having a T4SS secretion signal is context-dependent and unpredictable. Applicant furthers this traversal, asserting that the ordinary artisan would not have had a reasonable expectation of success in providing the functional fusion protein as claimed. In response, the Examiner respectfully submits that Vergunst et al is an evidentiary reference provided to show that Agrobacterium VirD2 proteins inherently comprise a T4SS secretion signal. However, it is of note that Sardesai et al disclose that the Agrobacterium VirD2 protein comprises a T4SS secretion signal and a DNA binding domain. See, for example, Paragraphs [0076] and [0079] of Sardesai et al. Therefore, the fusion protein as taught by Finer et al as evidenced by Vergunst et al, in view of Sardesai et al and Kim will not rely solely on the T4SS signaling domain for translocation, as it matches the structure of the fusion protein as claimed. Furthermore, the Examiner respectfully submits that it is not required that the expectation of success be a certainty; only one that is reasonable to a person of ordinary skill. In re Longi, 759 F.2d 887, 897 (Fed. Cir. 1985) (“Only a reasonable expectation of success, not absolute predictability, is necessary for a conclusion of obviousness”).
Applicant has lastly traversed the rejection, asserting in Pages 8-9 of the Remarks filed 21 May 2026 that the ordinary artisan would not have been able to reasonably substitute the Cas9 and Cas12a proteins since the disclosure of Kim utilizes a deadCas12a protein. In response, the Examiner respectfully submits that Kim teaches both a mutated, catalytically inactive form of the Cas12a protein (i.e., deadCas12a), as well as a functional Cas12a protein that is capable of generating double strand breaks. See, for example, Paragraphs [0102]-[0104] of Kim. Therefore, the ordinary artisan would have been able to reasonably substitute the Cas9 and Cas12a proteins within the fusion protein.
Therefore, the rejection is maintained and amended to encompass the claims as currently written.
Maintained Grounds of Rejection
Claim Interpretation
Instant claim 8 is directed to a fusion protein comprising an Agrobacterium effector protein having a DNA binding domain and a nucleic acid binding polypeptide, wherein the DNA binding domain of the fusion protein is capable of binding to a T-DNA sequence comprising a DNA homology repair template that comprises an edit for incorporation into a target nucleic acid. The Examiner is interpreting the recitation of “is capable of” to indicate that the binding of the binding domain of the fusion protein to the T-DNA is not materially required, and that the binding domain only has to be physically able to bind to the T-DNA at some point in time. Therefore, so long as the binding domain of the fusion protein is physically capable of binding to a T-DNA sequence comprising a DNA homology repair template that comprises an edit for incorporation into a target nucleic acid, it will read on the claim as written.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 8-10, 14, and 25-30 remain rejected under 35 U.S.C. 103 as being unpatentable over Finer et al (US 2019/0169624 A1, of record) as evidenced by Vergunst et al (PNAS, 2005, of record), in view of Sardesai et al (US 2016/0319291 A1, of record) and Kim (US 2021/0130827 A1, of record).
Finer et al is considered prior art under 35 USC 102(a)(1) and 35 USC 102(a)(2). Sardesai et al is considered prior art under 35 USC 102(a)(2), with a priority date of 30 October 2019. Kim is considered prior art under 35 USC 102(a)(2), with a priority date of 30 October 2019.
Regarding claims 8-10: Finer et al disclose a method for producing a genetically modified plant comprising inoculating a plant or plant cell with an Agrobacterium containing a nucleic acid of interest (Abstract; Paragraph [0058]).
As such, Finer et al disclose that Agrobacterium comprising transfer DNA (T-DNA) is used in conjunction with CRISPR-Cas9 genome editing techniques (Paragraphs [0047], [0053], [0082]-[0083], [0093]). Finer et al further disclose that the CRISPR-Cas9 genome editing protein is expressed in the Agrobacterium as a fusion protein, wherein the Cas9 effector protein – which reads on a nucleic acid binding protein – is fused to an appropriate domain of a virulence protein that is translocated into plants, such as the Agrobacterium VirD2 protein (Paragraphs [0082], [0087]). With that, Finer et al disclose that the genome editing proteins – including the Cas9/VirD2 fusion protein – can be used within an expression system to introduce a desired nucleotide sequence – or the T-DNA – into the target gene via homologous recombination (Paragraphs [0024], [0047], [0082], [0086]-[0087]).
It is of note that the Agrobacterium VirD2 protein will necessarily comprise a T4SS secretion signal, as evidenced by Pages 832, 835-837 and Figure 1 of Vergunst et al, 2005.
Finer et al do not disclose that the VirD2 protein comprises a DNA binding domain and a T4SS secretion signal comprising an amino acid sequence of SEQ ID NO: 166 or SEQ ID NO: 167, nor that the nucleic acid binding polypeptide comprises a Cas12a polypeptide, as required by instant claim 8.
However, in regards to the VirD2 protein comprising a DNA binding domain and a T4SS secretion signal that comprises an amino acid sequence of SEQ ID NO: 166 or SEQ ID NO: 167, Sardesai et al disclose a system of Agrobacterium-mediated plant transformation including plasmids containing transformation-enhancing genes within Agrobacterium strain (Abstract). As such, Sardesai et al disclose an Agrobacterium VirD2 protein having a sequence as set forth in SEQ ID NO: 19, which has 100% identity to instant SEQ ID NO: 166 (Paragraph [0079]). See sequence alignment below. It is of note that the sequence of Sardesai et al further supports that an Agrobacterium VirD2 protein will necessarily comprise a T4SS secretion signal. Sardesai et al further disclose that the Agrobacterium VirD2 protein is covalently bonded to the 5′ end of the T-strand complex, which indicates that the Agrobacterium VirD2 protein has a DNA binding domain for the T-strand complex (Paragraph [0076]).
Furthermore, in regards to the Cas12a polypeptide, Kim discloses type V CRISPR-Cas effector proteins, fusion nucleic constructs, and methods of targeted nucleic acid modification using the constructs thereof (Abstract). As such, Kim discloses a Cas12a effector protein that is comprised within an Agrobacterium, and aids in the modification of the target gene via the insertion of the corresponding T-DNA (Paragraphs [0040], [0074], [0088]-[0089], [0101]-[0104], [0164]-[0166]).
Therefore, it would have been prima facie obvious to have substituted both (i) the VirD2 protein within the VirD2/Cas9 fusion protein of Finer et al with the VirD2 protein as detailed in SEQ ID NO: 19 of Sardesai et al, and (ii) the Cas9 genome editing protein within the VirD2/Cas9 fusion protein of Finer et al with the Cas12a genome editing protein of Kim, as doing so would have been a simple substitution of one known VirD2 protein for another and one known Cas genome editing protein for another. See MPEP § 2143(I)(B). One of ordinary skill in the art before the effective filing date of the invention would have recognized that the two VirD2 proteins are functionally comparable, as both are Agrobacterium virulence proteins, and thereby would have been able to substitute the VirD2 proteins with predictable results. Likewise, the ordinary artisan would have recognized that the two Cas genome editing proteins are functionally comparable, as both are capable of being integrated into Agrobacterium and utilized for the insertion of T-DNA into a target gene, and thereby would have been able to substitute the Cas genome editing proteins with predictable results.
Consequently, Finer et al as evidenced by Vergunst et al and as modified by Sardesai et al and Kim render obvious a Cas12a/VirD2 fusion protein, wherein the CRISPR-Cas12a genome editing protein is fused to an appropriate domain of a virulence protein that is translocated into plants, including the Agrobacterium VirD2 protein (claims 9-10), wherein the VirD2 effector protein comprises a T4SS secretion signal set forth in instant SEQ ID NO: 166 and a DNA binding domain. As the DNA binding domain of the Cas12a/VirD2 fusion protein is physically capable of binding to a T-DNA nucleotide sequence that is incorporated into the target gene via homologous recombination, this therefore renders obvious the fusion protein of instant claim 8.
Query Match 100.0%; Matches 74; Mismatches 0; Indels 0; Gaps 0;
Qy 1 SGPLVRQAGTSRPSPPTATTRASTATDSLSATAHLQQRRGVLSKRPREDDDGEPSERKRE 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 374 SGPLVRQAGTSRPSPPTATTRASTATDSLSATAHLQQRRGVLSKRPREDDDGEPSERKRE 433
Qy 61 RDERSKDGRGGNRR 74 (INSTANT SEQ ID NO: 166)
||||||||||||||
Db 434 RDERSKDGRGGNRR 447 (SARDESAI ET AL SEQ ID NO: 19)
Regarding claim 14: Following the discussion of claim 8, Finer et al further disclose that the Cas/VirD2 fusion protein is comprised within an expression system (Paragraphs [0024], [0047], [0082], [0086]-[0087]). This therefore reads on the system of the instant claim.
Regarding claims 25-26: Following the discussion of claim 8, Finer et al further disclose that the genome editing protein – or Cas effector protein – is optionally treated to remove any purification tags, such as a His-tag, following expression within the plant cell (Paragraph [0086]). This therefore reasonably suggests that the Cas effector protein is fused to a His-tag (claim 26) prior to expression within the cell, and thereby reads on the fusion protein of instant claim 25.
Regarding claim 27: Following the discussion of claim 25, Kim further discloses that the type V CRISPR-Cas effector protein – or Cas12a polypeptide – is fused to a GCN4 peptide tag (Paragraphs [0132], [0136], [0143], [0164]). This therefore renders obvious the fusion protein of the instant claim for the same reasons as discussed in the rejection of claim 8.
Regarding claim 28: Following the discussion of claim 25, Kim further discloses that the type V CRISPR-Cas effector protein – or Cas12a polypeptide – is fused to an antibody (Paragraphs [0133], [0139], [0143]). This therefore renders obvious the fusion protein of the instant claim for the same reasons as discussed in the rejection of claim 8.
Regarding claims 29-30: Following the discussion of claim 8, Finer et al further disclose that the Agrobacterium effector protein is either fused to the N-terminus (claim 29) or C-terminus (claim 30) of the genome editing protein (Paragraph [0087], Page 980 of incorporated reference Vergunst et al, 2000). This therefore reads on the fusion protein of the instant claims.
Conclusion
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 ALYSSA G WESTON whose telephone number is (571)272-0337. The examiner can normally be reached Monday-Thursday 8AM - 4PM (CT); Friday 8AM - 11AM (CT).
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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.
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/ALYSSA G WESTON/Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633
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