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 .
Notice of Pre-AIA or AIA Status
This action is written in response to applicant’s correspondence received 23 January 2026. Claims 1-4, 6, 9-13, 15, 17-19, 28, 29, 32, 33, 37, 38, and 45-49 are currently pending. Claims 3, 4, 9, 10, 17, 37, and 38 are withdrawn from prosecution as being drawn to non-elected subject matter. Accordingly, claims 1-2, 6, 11-13, 15, 18-19, 28-29, 32-33, and 45-49 are examined herein. The restriction requirement mailed 5 December 2022 is still deemed proper. Applicant's elected Group I, claims 1-4, 6, 9-13, 15, 17-19, 28-29, and 31-33, alongside the species of claim 2, SEQ ID NO: 3, and SEQ ID NO: 24 without traverse in the reply filed 6 February 2023.
Applicant’s arguments, filed 23 January 2026, have been fully considered and are deemed persuasive.
Applicant alleges that Liu did not teach the use of a non-covalent recruitment of the Cas12a and deaminase domains. This argument is found persuasive. Therefore, the previously pending rejections under 35 USC 102 and 103 have been withdrawn.
Accordingly, this action is NON-FINAL.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 11-12, 28-29, 33, 45-47, and 49 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Kloiber-Maitz (US Patent No. 12,180,490 B2, filed 24 April 2019).
Regarding claim 1, Kloiber-Maitz is drawn towards an invention concerned with plants having improved digestibility (Abstract). Kloiber-Maitz teaches a method of base editing a target nucleic acid of interest comprising the usage of a base editor that can be linked to at least one site-specific effector via the use of a non-covalent linkage (Col. 25, line 56 to Col 26, line 8). Kloiber-Maitz teaches that the site-specific effector may be a DNA recognition domain of a CRISPR system (Col. 26, lines 2-8). Kloiber-Maitz teaches that the base editor may be a cytidine deaminase (Col 26, lines 38-43). Kloiber-Maitz teaches that a Cas effector protein is a site-specific homing endonuclease present within a CRISPR system that can target nucleic acids of interest via an RNA guide (i.e., a Cas protein is a DNA recognition domain of a CRISPR system) (Col 15, lines 56-66). Kloiber-Maitz teaches that the Cas protein may be a Cpf1 (Cas12a) protein (Col. 27, lines 16-17). Therefore, as described in MPEP 2131.02, one of ordinary skill in the art would have at once envisaged the use of a Cpf1 protein that was non-covalently linked to a cytidine deaminase because Kloiber-Maitz identifies well delineated options for the site-specific effector and base editor. Further, Kloiber-Maitz teaches that the site-specific effector is limited to DNA recognition domains of CRISPR systems, zinc fingers, or TAL effectors while the base editor is limited to proteins that can convert any one nucleotide to another nucleotide, and specifically teaches that cytidine deaminases are a preferred embodiment of a base editor. Therefore, the possible combinations of site-specific effectors and base editors taught by Kloiber-Maitz is sufficiently few such that one of ordinary skill in the art would have at once envisaged the use of a Cpf1 protein that was non-covalently linked to a cytidine deaminase.
Kloiber-Maitz teaches the use of a guide RNA that can direct the Cas protein to a target sequence of interest and specifically teaches that a guide RNA of the invention may be a guide RNA does not rely on the presence of a tracr sequence (e.g. if the Cas protein is Cpf1) (Col. 22, line 36 to Col. 23, line 15). Kloiber-Maitz teaches that the CRISPR effector protein may be mutated such that it lacks the ability to cleave one or both DNA or RNA strands of the target sequence such that the base editor (i.e., a deaminase) has the capacity to mediate a targeted base modification selected from introducing a point mutation of interest (i.e., the system can be utilized to introduce a base substitution) (Col. 25, line 56 to Col. 26, line 8).
Regarding claim 11, Kloiber-Maitz teaches that the CRISPR effector protein may be mutated such that it lacks the ability to cleave one or both DNA or RNA strands of the target sequence (i.e., the CRISPR effector comprises a mutation in a nuclease active site) (Col. 25, line 56 to Col. 26, line 8).
Regarding claim 12, Kloiber-Maitz teaches that the base editor may be a cytidine deaminase (i.e., a cytosine deaminase) (Col 26, lines 38-43).
Regarding claims 28-29, Kloiber-Maitz teaches that the CRISPR effector protein may be fused to a recombinase (i.e., a polypeptide of interest) (Col. 25, lines 56-61).
Regarding claims 33, 46-47, and 49, Kloiber-Maitz teaches that a method for obtaining a plant with increased digestibility may be accomplished via gene editing and/or base editing (i.e., via the introduction of the base editing system comprising the base editor and at least one site-specific effector (Col. 25, line 62 to Col. 26, line 8)) (Col. 50, lines 7-15). Kloiber-Maitz teaches that the term plant encompasses plant cells (Col. 11, lines 51-59).
Regarding claim 45, Kloiber-Maitz teaches that the Cas protein may be an AsCpf1 (i.e., an AsCas12a) protein (Col. 27, lines 24-29).
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.
Claim(s) 2 and 6 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kloiber-Maitz (US Patent No. 12,180,490 B2, filed 24 April 2019) as applied to claims 1, 11-12, 28-29, 33, 45-47, and 49 above, and further in view of Jacobsen (PG Pub No. WO 2018/136783 A1, published 26 July 2018).
Regarding claims 2 and 6, Kloiber-Maitz anticipates claims 1, 11-12, 28-29, 33, 45-47, and 49 as described above.
Kloiber-Maitz does not teach or suggest that the Cas12a polypeptide is fused to a peptide tag while the deaminase is fused to an affinity polypeptide that binds to the peptide tag (Claim 2). Kloiber-Maitz does not teach or suggest that the peptide tag is a Myc affinity tag, an HA affinity tag, a His affinity tag, a FLAG octapeptide, a V5 tag, or a VSV-G epitope (Claim 6).
However, one of ordinary skill in the art would have considered the teachings of Jacobsen as both references are common fields of endeavor pertaining to the use of peptide tags that are fused to fusion proteins.
Jacobsen is drawn towards an invention concerned with methods for using RNA-guided transcriptional activators to activate transcription of specific loci in plants (Abstract). Jacobsen teaches the use of a fusion protein comprising a nuclease-deficient Cas9 polypeptide (dCAS9) and a multimerized epitope, a second recombinant polypeptide including a transcriptional activator and an affinity polypeptide that specifically binds to the epitope ([0006]). Jacobsen teaches that the epitope and affinity polypeptide may be utilized as a linker between the dCas9 and recombinant polypeptide ([0057]). Jacobsen teaches that exemplary epitopes include a c-Myc affinity tag, an HA affinity tag, a His affinity tag, a FLAG octapeptide, a V5 tag, and a VSV-G epitope ([0080]).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the non-covalent linker between the Cpf1 and deaminase of Kloiber-Maitz for a linker comprising an epitope tag that can bind to an affinity polypeptide, as described by Jacobsen. A person of ordinary skill in the art would have had a reasonable expectation of success because both Kloiber-Maitz and Jacobsen teach the use of non-covalent linkers between a CRISPR protein and a heterologous protein of interest, such that the two proteins are recruited to one another.
Claim(s) 13, 15, 18-19, and 48 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kloiber-Maitz (US Patent No. 12,180,490 B2, filed 24 April 2019) as applied to claims 1, 11-12, 28-29, 33, 45-47, and 49 above, and further in view of Liu (US Patent No. 11,732,274 B2; filed 27 July 2018).
Regarding claims 13, 15, 18-19, and 48, Kloiber-Maitz anticipates claims 1, 11-12, 28-29, 33, 45-47, and 49 as described above.
Kloiber-Maitz does not teach or suggest that the target nucleic acid is contacted with two or more deaminase fusion proteins that comprise the same deaminase (Claim 13). Kloiber-Maitz does not teach or suggest that the deaminase is an APOBEC (Claim 15). Kloiber-Maitz does not teach or suggest that the method further comprises introducing a glycosylase inhibitor (Claim 18) selected from a UGI (Claim 19). Kloiber-Maitz does not teach or suggest that the glycosylase inhibitor and deaminase are separate components (Claim 48).
However, one of ordinary skill in the art would have considered the teachings of Liu as both references are common fields of endeavor pertaining to the use of Cas12a polypeptides, deaminases, and guide RNAs in order to target and edit a nucleic acid of interest.
Liu is drawn towards an invention concerned with a method of using an evolved base editors in order to edit a target nucleic acid molecule (Col 2, line 61 to Col 3, line 2). Liu teaches that the evolved base editor comprises a nucleic acid programmable DNA binding protein (i.e., a napDNAbp) selected from Cpf1 (i.e., Cas12a) (Col. 4, lines 54-65). Liu teaches that the evolved base editor comprises a guide RNA that can bind to the napDNAbp (Col 7, lines 6-16). Liu teaches that the evolved base editor may comprise the following structure: A-B-C, wherein “A” is a napDNAbp, “B” is nucleic acid effector domain (e.g., a deaminase, such as a cytidine or adenosine deaminase), and “C” represents an optional additional base editor functional domain (e.g., a UGI domain or a NLS domain) (Col 48, lines 15-31). Liu teaches that vectors encoding the evolved base editors may be transfected into one or more cells (i.e., Liu is interpreted as teaching that multiple vectors encoding multiple evolved base editors may be transfected into a single cell) in order to treat a diseased eukaryotic cell (Col 106, lines 16-24). Liu teaches that an APOBEC deaminase may be utilized as a deaminase in the invention (Col 8, lines 10-20). Liu teaches that a UGI may be utilized alongside the base editor in order to increase the efficiency and stability of the resulting nucleotide change (Col. 1, lines 44-47). Liu teaches that the glycosylase inhibitor and the deaminase domain are separate components (Col 48, lines 15-31).
Therefore, regarding claim 13, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method anticipated by Kloiber-Maitz such that the target nucleic acid is contacted with a vector encoding two or more deaminase fusion proteins that comprise the same deaminase, as described by Liu. A person of ordinary skill in the art would have been motivated to do so in order to utilize a known method of delivering base editing systems to eukaryotic cells in order to treat a disease of interest. A person of ordinary skill in the art would have had a reasonable expectation of success because both Kloiber-Maitz and Liu teach the use of base editor systems comprising a Cas12a polypeptide, a deaminase, and a guide RNA.
Therefore, regarding claims 18-19 and 48, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method anticipated by Kloiber-Maitz such that a UGI, that is a separate component than the deaminase is utilized alongside the base editing system, as described by Liu. A person of ordinary skill in the art would have been motivated to do so in order to increase the efficiency and stability of a resulting nucleotide change induced by the system. A person of ordinary skill in the art would have had a reasonable expectation of success because both Kloiber-Maitz and Liu teach the use of base editor systems comprising a Cas12a polypeptide, a deaminase, and a guide RNA.
Claim(s) 32 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kloiber-Maitz (US Patent No. 12,180,490 B2, filed 24 April 2019) as applied to claims 1, 11-12, 28-29, 33, 45-47, and 49 above, and further in view of Begemann (PG Pub No. US 2017/0233756 A1).
Regarding claim 32, Kloiber-Maitz anticipates claims 1, 11-12, 28-29, 33, 45-47, and 49 as described above.
Liu does not teach or suggest that the Cas12a polypeptide has a sequence selected from the claimed SEQ ID NO: 3 (Claim 32).
However, one of ordinary skill in the art would have considered the teachings of Begemann as both references are common fields of endeavor pertaining to the use of Cas12a polypeptides.
Begemann is drawn to an invention concerned with modifying target DNA (Abstract). Begemann teaches the use of a fusion protein comprising a deactivated Cpfl polypeptide (i.e., a Cas12a polypeptide) having 100% sequence identity to the claimed SEQ ID NO: 3 and an effector domain ([0030]-[0031]; see SEQ ID NO: 36 in previously attached sequence alignment). Begemann teaches that the Cpf1 polypeptide can be utilized to direct the fusion protein to a target nucleic acid via the use of a guide RNA in order to modify the target nucleic acid ([0030]). Begemann teaches that the fusion protein can be introduced into and expressed within a plant cell in order to modify or introduce exogenous sequences within the plant cell’s genome ([0014]). Begemann teaches that modifying a plant cell’s genome is of immense importance to both basic and applied plant research because it allows for the introduction of new traits into the plant cell such as herbicide tolerance, insect resistance, and/or accumulation of valuable proteins including pharmaceutical proteins and industrial enzymes imparted to them ([0004]).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the deactivated Cpf1 of Kloiber-Maitz for a deactivated Cpf1 having 100% sequence identity to the claimed SEQ ID NO: 3, as described by Begemann. A person of ordinary skill in the art would have had a reasonable expectation of success because both Kloiber-Maitz and Begemann teach the use of deactivated Cpf1 proteins that can be utilized in fusion proteins in order to direct the fusion protein to a target site via the use of a guide RNA.
Response to Arguments
Applicant’s arguments, filed 23 January 2026, have been fully considered and are deemed persuasive.
Applicant alleges that Liu did not teach the use of a non-covalent recruitment of the Cas12a and deaminase domains. This argument is found persuasive. Therefore, the previously pending rejections under 35 USC 102 and 103 have been withdrawn.
Insofar as Applicant’s arguments pertain to the newly recited rejections of record of record, the currently pending rejections of record reply on Liu, Jacobsen, and Begemann for the teachings of dependent claims that were not addressed in the arguments filed 23 January 2026.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KYLE T REGA whose telephone number is (571)272-2073. The examiner can normally be reached M-R 8:30-4:30, every other F 8:30-4:30 (EDT/EST).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Neil Hammell can be reached at 571-270-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KYLE T REGA/Examiner, Art Unit 1636
/NEIL P HAMMELL/Supervisory Patent Examiner, Art Unit 1636