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
This action is written in response to applicant’s correspondence received April 13, 2026. Claims 1, 5, 10-11, and 16 were amended in the claim set filed April 13, 2026. Claim 8 is cancelled. Accordingly, claims 1-7, and 9-16 are currently pending and under consideration.
Any rejection or objection not reiterated herein has been overcome by amendment. 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.
Priority
Acknowledgment is made of Applicant’s claim for priority based on a US Provisional Application No. 63/088,420 filed on 06 Oct 2020. Support for amended claim 1 is found in Example 1. Support for amended claim 5 is found in [0054]. Support for amended claim 10 is found in [0082] reciting “a homology sequence is a sequence that shares or complete or partial homology with target sequence at the site the targeted site of insertion and/or guide molecule”. Support for amended claim 11 is found in [0014].
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 1-7, 9, 11-13, and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Hummel et al (US 2021/0171947 A1; Filed Date: 6 Dec 2020; PRO 62/944,976 Filed Date: 6 Dec 2019; hereinafter as Hummel). This is a new rejection necessitated by amendments.
Regarding claim 1, Hummel teaches an engineered composition comprising all the components in the claimed invention: a nucleic acid binding protein (e.g., a CRISPR-Cas effector protein) (i.e., site-specific nuclease polypeptide), a guide nucleic acid, an Agrobacterium effector protein, a DNA-dependent DNA polymerase, and optionally a T-DNA contact a target nucleic acid to thereby modify the nucleic acid ([0102]). Hummel teaches a DNA-dependent DNA polymerase is also directly fused to the CRISPR Cas effector protein, which directs the DNA-dependent DNA polymerase to be in vicinity of the target nucleic acid ([0102]). Hummel further teaches the function of the DNA-dependent polymerase is to incorporate the T-DNA sequence into the genomic target site as the T-DNA may comprise a primer binding site having complementarity to the 3’ end of a nick in the genomic target site ([0240]). Further, the DNA-dependent DNA polymerase could be endogenous or transgenic ([0240]). Hummel further teaches one of the exemplary Agrobacterium effector proteins is VirD2 ([0160]), and CRISPR Cas effector protein is directly fused to Agrobacterium effector proteins ([0173]). Hummel also teaches a guide nucleic acid is capable of forming a complex with CRISPR-effector protein, thereby guiding the CRISPR-Cas fusion protein (Cas effector and Agrobacterium effector), and optionally T-DNA associated with Agrobacterium effector, to the target nucleic acid ([0021]).
However, Hummel does not teach the claimed arrangement wherein the DNA polymerase is fused to or connected by a linker to the site-specific nuclease polypeptide and the VirD2 polypeptide is also fused to or connected by a linker to the site-specific nuclease polypeptide.
Hummel does teach the following embodiments: i) a VirD2 fused to or connected by a linker to a CRISPR Cas effector protein ([0160], [0102]), ii) a DNA-dependent DNA polymerase fused to or connected by a linker also to a CRISPR Cas effector protein ([0102]), and iii) in which the VirD2, CRISPR Cas effector protein, and DNA-dependent DNA polymerase, are localized at the target nucleic acid through covalent interactions ([0102]; pg. 11, end of col. 2). Thus, Hummel expressly recognizes localization of these three components together at the target nucleic acid as a functional complex, and one of the possible embodiments is the claimed arrangement.
Thus, it would have been obvious to one of ordinary skill in the art before the effective filling date of the invention to have covalently linked the VirD2, CRISPR Cas effector protein, and DNA-dependent DNA polymerase in the claimed arrangement because it would have merely amounted to a simple suggestion or motivation taught by Hummel. Hummel already teaches fusion of the CRISPR Cas effector protein to the DNA-dependent DNA polymerase and VirD2 individually, thereby providing a positive suggestion to use the CRISPR Cas effector protein as the main component in which the DNA-dependent DNA polymerase and VirD2 can be fused to. In view of these teachings, one would have been motivated to have done so for the advantage of colocalizing all three components at the target nucleic acid simultaneously as suggested by Hummel ([0102]; pg. 11, end of col. 2). One would have had a reasonable expectation of success in doing so because Hummel teaches these three components function cooperatively when localized to the target nucleic acid, and Hummel teaches that DNA-dependent DNA polymerase and VirD2 can each be fused to the CRISPR Cas effector protein while retaining their intended function; thus, combining known fusion arrangements into a single fusion complex would reasonably expect each component to perform its established function at the target nucleic acid.
Regarding claim 2, Hummel teaches a T-DNA (i.e., donor construct) is capable of forming a complex with the VirD2 protein which Tyr29 covalently attaches to the 5'-end of the T-DNA and nuclear localization signal transfers the T-DNA into the nucleus ([0157]). Hummel further teaches the T-DNA comprises a homology repair template that may be used for modifying a target nucleic acid [0161], and DNA-dependent DNA polymerase "may be utilized to incorporate the edit" ([0167] and [0240]).
Regarding claim 3, Hummel teaches wherein the T-DNAs are ssDNA molecules ([0155]), and contains left and right borders (i.e., binding sequences) for VirD1 and VirD2 proteins ([0157]).
Regarding claim 4, Hummel teaches that T-DNA is harbored as a double-stranded sequence encoding left and right borders (i.e., 5’ and 3’ boundary sequences) for VirD1 and VirD2 proteins to associate, nick, and release the T-DNA as ssDNA molecules, and VirD2 protein remains covalently attached at Tyr29 to the 5'-end of the T-DNA and guides the transfer of T-DNA into the nucleus ([0157]). Although Hummel does not explicitly teach a donor polynucleotide sequence located between the 5’ and the 3’ boundary sequences, such configuration is inherent in donor templates used for homology-directed repair (HDR) (see teachings discussed above in claim 2) and T-DNA natural transfer process in Agrobacterium ([0157]). As is well understood by a person ordinary skill in the art, T-DNA processed by VirD1 and VirD2 necessarily comprise the donor sequence positioned between the 5’ and 3’ borders. Thus, Hummel disclose inherently a donor sequence located between the 5’ and the 3’ boundary sequences.
Regarding claim 6, Hummel teaches wherein the T-DNA further comprises a 3' and/or 5' homology region with sequences complementarity to target nucleic acid ([0237]).
Regarding claim 7, Hummel teaches wherein the T-DNA may have a length of about 400 to 30,000 nucleotides ([0235]).
Regarding claim 9, Hummel teaches wherein the composition comprises a CRISPR-Cas effector fusion protein and a CRISPR guide nucleic acid "capable of forming a complex with the CRISPR-Cas effector protein", and which "spacer sequence is capable of hybridizing to a target nucleic acid, thereby guiding the CRISPR-Cas fusion protein to the target nucleic acid" ([0021]).
Regarding claim 11, Hummel teaches wherein the CRISPR-Cas effector protein is a nickase that is configured to nick a site on the first or second strand of the target nucleic acid ([0211]).
Regarding claim 12, Hummel teaches the composition further comprises a second guide nucleic acid capable of forming a complex with another CRISPR-Cas effector protein that nicks a site on the first strand of the target nucleic acid (i.e., non-targeted strand) near a second site on the second strand that has been nicked by a different CRISPR-Cas effector protein (targeted strand) ([0213]).
Regarding claim 13, Hummel teaches wherein the VirD2 is derived from Agrobacterium tumefaceins ([0302]).
Regarding claim 16, Hummel teaches a single expression cassette encoding a CRISPR-Cas effector protein (i.e., site-specific nuclease), an Agrobacterium effector protein (i.e., VirD1 and VirD2), a DNA dependent polymerase or a 5'-3' exonuclease polypeptide, a T-DNA sequence (i.e., donor), and/or a guide nucleic acid ([0096]).
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Hummel et al (US 2021/0171947 A1; Filed Date: 6 Dec 2020; PRO 62/944,976 Filed Date: 6 Dec 2019; hereinafter as Hummel) as applied to claim 1 above, and further in view of Relic et al (Interaction of the DNA modifying proteins VirD1 and VirD2 of Agrobacterium tumefaciens: Analysis by subcellular localization in mammalian cells; PNAS, 1998, 95:9105-9110). This is a new rejection necessitated by amendments.
Regarding claim 5, the teachings of Hummel on a fusion protein comprising a site-specific nuclease polypeptide (e.g., CRISPR protein), a DNA polymerase, and a VirD2 polypeptide are discussed above as applied to claim 1. Hummel further teaches a T-DNA/VirD2 associated complex may be recruited to a specific genomic site with CRISPR proteins. In this strategy, T-DNA complex recruitment may be evaluated in heterologous systems, including human and plant cells, by co-expressing VirD1 and VirD2 fused to a recruitment domain ([0229]), because the natural transfer process in Agrobacterium cells involves VirD1 and VirD2 functioning together by associating with each end of the T-DNA, nick it, and releasing it as a ssDNA molecule ([0157]. Thus, Hummel positively teaches incorporation of VirD1 is essential in delivering a DNA molecule at a specific genomic site via interactions with CRISPR proteins.
However, Hummel does not explicitly teach wherein the VirD1 polypeptide is fused or connected by a linker to the VirD2 polypeptide.
Relic et al teach VirD1 and VirD2 interact together and play a role in both recognition and processing of T-DNA in Agrobacterium, demonstrated by coimmunoprecipitation analysis and direct immunofluorescence (pg. 9110, col. 1, para. 2; Fig. 5). Relic et al demonstrate that cell expressing cytoplasmic fusion protein of a green fluorescent protein (GFP) fused to VirD1 was translocated to the nucleus when VirD2 is co-expressed in the cell (caption of Fig. 5B) because VirD2 protein bears two nuclear localization signals (pg. 9105, col. 2, para. 2). Relic et al further demonstrate that GFP, VirD1, and VirD2, three proteins when all fused in frame are also translocated to the nucleus via the NLS on VirD2, supporting that VirD1 and VirD2 fusion is predictable.
Thus, it would have been obvious to one of ordinary skill in the art before the effective filling date of the invention to have modified the fusion protein (e.g., CRISPR-DNA-dependent polymerase-VirD2) of Hummel to fuse VirD1 to the VirD2 taught by Relic et al because it would have merely amounted to a simple combination of prior art elements according to known methods to yield predictable results. As Hummel teaches, VirD1 and VirD2 function together and it is important to evaluate T-DNA complex recruitment by co-expressing both VirD1 and VirD2, thereby recognizing that VirD1 and VirD2 function cooperatively during T-DNA processing and delivery in the nucleus. Further, Relic et al teach that “VirD1 protein, by itself localized in the cytoplasm, moved to the nucleus when coexpressed with the VirD2 protein”, as a result of their interactions, demonstrating that VirD1 and VirD2 can be physically linked while retaining the ability to localize to the nucleus together (abstract). In view of these teachings, one would have been motivated to have done the modification for the advantage of predictably ensuring that both proteins are delivered together to the same intracellular location and maintained at a defined stoichiometry to facilitate T-DNA processing effectively and efficiently at the CRISPR-targeted locus. One would have had a reasonable expectation of success in doing so because Relic et al demonstrates that the fusion protein comprising VirD1 either directly fused to VirD2 or via protein-protein interactions can both be colocalized in the nucleus to perform their established functions.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Hummel et al (US 2021/0171947 A1; Filed Date: 6 Dec 2020; PRO 62/944,976 Filed Date: 6 Dec 2019; hereinafter as Hummel) as applied to claim 6 above, and further in view of Anzalone et al (Search-and-replace genome editing without double-strand breaks or donor DNA; Nature, 2019, 576:149-157). This is a new rejection necessitated by amendments.
Regarding claim 10, the teachings of Hummel’s fusion protein is discussed above as applied to claim 6. Hummel further teaches the T-DNA (i.e., donor construct) comprises a short primer binding site complementary to the 3’ end of a nick in a genomic target site “for use in an application somewhat like “prime editing”” ([0167], [0240]). Hummel further teaches the “DNA-dependent DNA polymerase rather than reverse transcriptase may be utilized to incorporate the edit” ([0167]).
However, Hummel does not teach wherein the homology sequence in the T-DNA is complementary to at least a portion of the guide polynucleotide.
Anzalone et al teach an engineered composition comprising a CRISPR Cas9 site-specific nuclease fused to or connected by a linker to a reverse transcriptase, and a peg-RNA (i.e., guide polynucleotide) (Fig. 1c, illustrated below). Anzalone et al further teach the pegRNA comprises of a primer-binding site complementary to the 3’ end of the strand nicked by the CRISPR Cas9 nickase (caption of Fig 1c). Anzalone et al also teach upon hybridization of the primer-binding site, reverse transcriptase incorporates desired edits into the target nucleic acid through direct polymerization.
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Thus, it would have been obvious to one of ordinary skill in the art before the effective filling date of the invention to have modified the short primer binding site of Hummel’s T-DNA to be complementary to at least a portion of the guide polynucleotide or peg-RN as taught by Anzalone et al because it would have merely amounted to a simple combination of prior art elements according to known methods to yield predictable results. In this modification, each element merely performs the same function as it does separately – the T-DNA comprises a homology region complementary to the target nucleic acid, specifically to the 3’ end of a nick in a genomic target site (Hummel [0237]), the guide polynucleotide comprises sequence complementary to the genomic target site and scaffold capable of forming a complex with the CRISPR Cas effector protein (Hummel [0021] and Anzalone Fig. 1c), and the DNA-dependent polymerase incorporates the edit on the nicked DNA strand (Hummel [0167]). One would have been motivated to have done so for the advantage of enhancing coordination between the T-DNA carrying the desired edits and the CRISPR fusion proteins, thereby facilitating efficient incorporation of the edits into the target nucleic acid. One would have had a reasonable expectation of success in doing so because Hummel already teaches the T-DNA is for use in an application similar to prime editing of Anzalone et al ([0167], [0240]), and both Hummel and Anzalone et al employ CRISPR Cas fusion proteins to target a genomic site and utilize a nucleic acid template (T-DNA and pegRNA, respectively) to install modifications of a desired sequence at the target site.
Claims 14 and 15 are rejected under 35 U.S.C. 102(a)(2) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Hummel et al (US 2021/0171947 A1; Filed Date: 6 Dec 2020; PRO 62/944,976 Filed Date: 6 Dec 2019; hereinafter as Hummel), in view of Halperin et al (WO 2019/051097 A1; Published Date: 14 Mar 2019; hereinafter as Halperin)
Regarding claim 14 and 15, the teachings of Hummel regarding the composition of claim 1 is discussed and applied above to claim 1. Hummel further teaches wherein the DNA-dependent polymerase is a domain thereof or a 5'-3' exonuclease polypeptide or domain thereof ([0096]).
Hummel does not explicitly teach wherein the DNA-dependent polymerase is an DNA Poly I polymerase or an E. coli DNA polymerase, but DNA-dependent polymerase is a broad genus of enzymes including, not limited to, DNA polymerase I, polymerase III, and reverse transcriptase.
Halperin teaches a fusion protein of a Cas9 nickase (nCas9) and a E. coli DNA polymerase I mutant to introduce mutations during efficient homology-directed repair integration (Abstract and [00346]).
Thus, it would have been obvious to one of ordinary skill in the art before the effective filling date of the invention to have modified the DNA-dependent polymerase in the composition of Hummel with an E. coli DNA polymerase as taught by Halperin, because it would have merely amounted to a simple substitution of prior art elements according to known methods to yield predictable results. One would have been motivated to have done so for the advantage of 5’-3’ exonuclease function of E. coli DNA polymerase in addition to its nucleotide filling and proofreading capabilities during polynucleotide repair and synthesis. One would have had a reasonable expectation of success in doing so because both Hummel and Halperin teaches a composition of fusion proteins comprising CRISPR-Cas effector and DNA polymerase, and their applications in genome editing.
Response to the Arguments
Applicant argues that “Hummel does not disclose this tri-component fusion. At [0102], Hummel’s components “localize at the target nucleic acid, optionally through covalent and/or non-covalent interactions” -describing various co-localization mechanisms without specifying that DNA polymerase and VirD2 are both covalently fused to the same nuclease via peptide bonds”. Applicant’s arguments, see pg. 9, section I, para. 2, filed April 13, 2026, with respect to the rejection(s) of claim(s) 1-7, 9, 11-13, and 16 under 35 U.S.C. 102(a)(2) have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made over Hummel (US 2021/0171947 A1; Filed Date: 6 Dec 2020; PRO 62/944,976 Filed Date: 6 Dec 2019; hereinafter as Hummel), see section 9.
Applicant argues that “Hummel does not teach VirD1 fused to VirD2” and [a]mended claim 5 requires “the VirD1 polypeptide is fused to the VirD2 polypeptide" Applicant’s arguments, see pg. 9, section II, filed April 13, 2026, with respect to the rejection(s) of claim(s) 10 under 35 U.S.C. 102(a)(2) have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made over Hummel (US 2021/0171947 A1; Filed Date: 6 Dec 2020; PRO 62/944,976 Filed Date: 6 Dec 2019; hereinafter as Hummel) in view of Relic et al (Interaction of the DNA modifying proteins VirD1 and VirD2 of Agrobacterium tumefaciens: Analysis by subcellular localization in mammalian cells; PNAS, 1998, 95:9105-9110), see section 10.
Applicant argues that “[t]his engineered fusion ensures stoichiometric 1: 1 ratio of VirD1:VirD2 activities, eliminates dependency on transient protein-protein interactions, maintains the activities in fixed spatial proximity, and creates a single entity for subsequent fusion to the nuclease polymerase complex” (pg. 9, last paragraph), “[t]he structural difference between the claimed integrated
fusion protein and Hummel's modular recruitment system represents a patentable distinction” (pg. 10, section III, para. 2), and “[t]he claimed fusion protein provides structural and functional advantages through coordinated delivery of all components as an integrated complex” (pg. 10, section III, para. 3).
Applicant’s arguments have been fully considered but are not persuasive because although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Further, MPEP § 2145(II) notes that prima facie obviousness is not rebutted by merely recognizing additional advantages or latent properties present but not recognized in the prior art. In this case, as stated in the instant Office Action, section 10, Hummel positively suggests co-expressing VirD1 and VirD2 in the host cell because the natural transfer process of T-DNA involves VirD1 and VirD2 functioning together ([0157]) and Relic et al teaches that upon protein-protein interactions between of VirD1 and VirD2, VirD1 is translocated to the nucleus, given that it lacks a nuclear localization signal as opposed to VirD2 (Fig. 5). Thus, it would have been obvious to have combined prior art teachings to fuse or covalently connect VirD1 to VirD2, because it would have merely amounted to a simple combination of prior elements according to known methods to yield predictable results, considering that Relic et al teach fusion of VirD1 and VirD2 in 1:1 stoichiometric ratio is successfully translocated together to the nucleus. See instant section 10 for further discussion. Thus, any purported advantages that result from the claimed structure would also flow naturally from the prior art combination.
Applicant argues that “[t]he claimed invention requires accurate, template-directed DNA synthesis to achieve precise genomic integration of donor sequences. The specification describes a mechanism…this process demands high-fidelity synthesis to ensure accurate incorporation of intended donor sequence without introducing unwanted mutations (pg. 12, section II, para. 2), “combining Hummel's system with Halperin's error-prone polymerase would be counterproductive”, and “[a] skilled artisan seeking to achieve precise genomic editing would not select a polymerase specifically engineered to maximize error” (pg. 12, section II, para. 3).
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., accurate, template-directed DNA synthesis to achieve precise genomic integration of donor sequences) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). The instant claims 14 and 15 requires an engineered composition comprising a) a site-specific nuclease polypeptide fused to or connected by a linker to b) a DNA polymerase that is a DNA Pol I or an E. coli DNA polymerase, and c) a VirD2 polypeptide. The combination of Hummel and Halperin teach this engineered composition. As explained in the previous Office Action mailed on January 13, 2026, and instant Office Action section 12 that it would have been obvious to modify Hummel’s composition comprising the recited a) b) and c) components into a single fusion protein via covalent linkers for the advantage of localizing all components together at the target nucleic acid, and it would have also been obvious to modify Hummel’s DNA-dependent DNA polymerase that incorporates edits from the T-DNA into a genomic target site ([0167], [0240]), to an E. coli DNA polymerase I of Halperin. Hummel utilized DNA-dependent DNA polymerase’ nucleotide filling function to incorporate edits, which under the broadest reasonable interpretation, Hummel teaches a genus of DNA polymerases encompassing any DNA polymerase that performs this function to introduce any edits including any mutations, insertions, and deletions. If one of ordinary skill in the art seeking to achieve genomic editing using the engineered composition of Hummel, it would have been obvious to search in the art for specific species within the recited genus and would have arrived at Halperin’s E. coli DNA polymerase I, wild-type or mutant because Halperin demonstrates that this particular DNA polymerase can be fused to CRISPR Cas effector protein, and the substituted components (generic DNA polymerase of Hummel to a particular E. coli DNA polymerase I of Halperin) and their functions were known and demonstrated in fusion with a site-specific nuclease in the art. This modification is a substitution of similar features that serve the same purpose, synthesizing the sequence from the T-DNA into the genomic target site.
Applicant argues that “one of ordinary skill in the art would not have been motivated to incorporate Halperin's specific DNA polymerase I variant into such a system” and “Halperin's entire disclosure focuses on using this error-prone polymerase for random mutagenesis and targeted gene evolution where the goal is to increase error rates and generate libraries harboring random mutations.” (pg. 11, section II, para. 1).
In response to applicant's argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). Further, if the prior art as a whole teaches some suggestion to combine the elements, it is not required that these elements be combined for the same motivation as the Applicant's stated purpose of “precise genomic editing” and “accurate, template-directed DNA synthesis” (see MPEP 2141.02).
As explained above, Hummel positively teaches a fusion protein comprising a CRISPR Cas effector protein and DNA-dependent DNA polymerase (e.g., genus) also to achieve template-directed DNA synthesis in a manner similar to prime editing ([0167], [0240]), which does require precise genomic integration of donor sequences. Therefore, Hummel does teach suggestion and the same motivation as Applicant’s stated purpose. As explained above, it would have been prima facie obvious to arrive at Halperin’s E coli. DNA polymerase I if one of ordinary skill in the art desires to search for a specific DNA polymerase and if the error-prone function of Halperin’s DNA polymerase I variant is not desired, it would have merely amounted to a simple substitution of DNA polymerase to utilize Halperin’s E. coli DNA polymerase I wild-type, without engineered mutations.
Applicant’s arguments have been fully considered but they are not persuasive as explained in sections 16 and 17. Therefore, 35 U.S.C. 103 rejection over claims 14 and 15 is maintained.
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.
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/QIWEN SU-TOBON/
Examiner
Art Unit 1636
/NEIL P HAMMELL/Supervisory Patent Examiner, Art Unit 1636
Prosecution Insights