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 .
DETAILED ACTION
Claims 1-2, 4-7, 9, 11-15, 20-21, 23-24, 26-29, 31, 33-36, 45-46, 55-56, 62-71, 75, 77, 80, 85-86, 88, and 91-93 are pending.
Election/Restrictions
Applicant’s election of Group I, claims 1-2, 4-7, 9, 11-15, 20-21, 23-24, 26-29, 31, 33-36, and 45, and the species of amino acid substitution sets l509R or l509S with S511N, Ll24K, and E219K and a TALE domain in the reply filed on 2/9/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 46, 55-56, 62-71, 75, 77, 80, 85-86, 88, and 91-93 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 2/9/2026.
No prior art was found on Applicant’s elected species of combination of amino acid substitutions (l509R or l509S with S511N, Ll24K, and E219K), so all non-elected species were also searched.
Claims 1-2, 4-7, 9, 11-15, 20-21, 23-24, 26-29, 31, 33-36, and 45 are examined herein.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. See [0067] of the specification.
Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Drawings
The drawings are objected to because the grayscale adaptation of Fig. 2 does not allow the reader to interpret the data. The specification indicates that different colors representing BAD, AVG, and GOOD indicate the different conservation qualities of protein sequences (Specification [0021]). Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claim 27 is objected to because of the following informalities: “Specific end Binding Domain.” End should be capitalized for consistency with claim 6.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 5, 7, 13-14, 28, and 34-36 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 5, 7, 13-14, 28, and 34-35 each recite amino acid substitutions without a reference sequence. Therefore, it is unclear whether these amino acid substitutions are relative to SEQ ID NO: 1, which is recited in independent claims 1 and 20, or whether these amino acid substitutions are relative to another amino acid sequence.
Claim 36 is indefinite for “wherein the SPIN transposase sequence comprises one or more of the following groups of amino acid substitutions when numbered in accordance with SEQ ID NO: 1: I509R, Ll24K, E219K, and S511N; I509R and Ll24K; I509R, Ll24K, and E219K; I509R and E219K; Ll24K and E219K; I509R and Ll24K; S511N, Ll24K, and E219K; S511N and E219K; or Ll24K and S511N. The combination of “one or more” with a list of alternatives separated by “or” leads to ambiguity in the claim scope as it is unclear whether combinations of the alternatives are within the claim scope or not. Applicant may consider replacing “or” with “and” in the list of alternatives.
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 1-2, 4-7, 9, 11-15, 20-21, 23-24, 26-29, 31, 33-36, and 45 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 claims 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 inventors, at the time the application was filed, had possession of the claimed invention.
Independent claim 1 recites “A mutant SPIN transposase comprising an amino acid sequence at least 70% identical to full-length SEQ ID NO: 1 and having increased transposition efficiency in comparison to a wild-type SPIN transposase having amino acid sequence SEQ ID NO: 1.” Claims 2, 4-7, 9, and 11-15 depend from claim 1. Claim 2 recites “The mutant SPIN transposase of claim 1, comprising one or more amino acid substitutions that increase a net charge at a neutral pH in comparison to SEQ ID NO: 1.”
Independent claim 20 recites “A fusion transposase comprising a SPIN transposase sequence and a DNA sequence specific binding domain, wherein the SPIN transposase sequence has at least 70% identity to full-length SEQ ID NO: 1.” Claims 21, 23-24, 26-29, 31, 33-36, and 45 depend from claim 20. Claim 24 recites “The fusion transposase of claim 20, wherein the SPIN transposase sequence comprises one or more amino acid substitutions that increase a net charge at a neutral pH in comparison to SEQ ID NO: 1.” Claim 29 recites that the SPIN transposase sequence has increased transposition efficiency in comparison to a wild-type SPIN transposase having amino acid sequence SEQ ID NO; 1.
SEQ ID NO: 1 is 602 amino acids long. Therefore, an amino acid sequence with at least 70% sequence identity to SEQ ID NO: 1 has up to 180 amino acid substitutions.
The person of ordinary skill in the art would not have recognized that the inventors, at the time the application was filed, had possession of the claimed genus of mutant SPIN transposases having increased transposition efficiency in comparison to SEQ ID NO: 1. The person of ordinary skill in the art would also not have recognized that the inventors had possession of the claimed genus of fusion SPIN transposase variants.
The specification discloses 25 species of mutant SPIN transposase. Each of the mutants has a single amino acid point mutation except for the combination of I509R + S511R. The specification also discloses that only 5 of the mutants have a transposition efficiency greater than the wild-type transposase ([00132]). The specification also discloses the hypothesis that substitutions to a positively charged amino acid such as lysine or arginine in proximity to one of the catalytic triad amino acids (D185, D251, and E555) increases transposition efficiency ([00133]). Fig. 5 depicts the wildtype SPIN transposase amino acid sequence with the catalytic triad amino acids and large italicized lettering indicating amino acids that when substituted to a positively charged amino acid increase transposition efficiency ([00134]). Fig. 5 also depicts amino acids that allegedly could be positively charged amino acids based on the protein sequence alignment to the Buster subfamily ([00134]). The Buster subfamily alignment is depicted in Fig. 2. The Buster subfamily is a subfamily of the hAT transposons ([0004]). The specification does not disclose whether the other members of the Buster subfamily have been tested for transposase activity, or whether these are putative transposases.
In total, three amino acid substitutions support the hypothesis that positively charged amino acids in the vicinity of the catalytic triad increase transposition efficiency. However, claim 9 recites “one or more amino acid substitutions that increase a net charge at a neutral pH in comparison to SEQ ID NO: 1, wherein the one or more amino acids are located in proximity to Dl85, D251, or E555, when numbered in accordance to SEQ ID NO: 1.” Claim 11 recites “wherein the proximity is a distance of about 5 to 80 amino acids.” There are an insufficient number of species of positively charged amino acid substitutions in proximity to Dl85, D251, or E555 that increase transposition efficiency of the SPIN transposase mutant relative to SEQ ID NO: 1 for the person of ordinary skill in the art to reasonably predict and visualize the structures of all the species within the claimed genus.
Therefore, although the specification attempts to establish a structure-function relationship between the property of increased transposition efficiency relative to SEQ ID NO: 1, there is insufficient evidence of record to support the claimed genus because of the small number of mutants that actually have increased transposition efficiency relative to SEQ ID NO: 1 (Fig. 4) as well as the lack of functional information disclosed regarding the sequences of the alignment in Fig. 2. An alignment of many hypothetical proteins with only a few characterized proteins would not be sufficient to support a structure-function relationship of the entire class of SPIN transposase proteins.
Regarding independent claim 20, although the claim does not require increased transposition efficiency relative to SEQ ID NO: 1, the claim still implicitly requires transposase activity because the claim preamble recites “a fusion transposase.” Given the lack of structure-function information provided in the specification as well as the state of the prior art (discussed below), the person of ordinary skill in the art would have been unable to reasonably predict and visualize structures of all the species within the claimed genus, which includes fusion transposases comprising a SPIN transposase with up to 180 amino acid substitutions relative to full-length SEQ ID NO: 1.
Pace et al. (Proceedings of the National Academy of Sciences 105.44 (2008): 17023-17028) teaches a class of transposons called Space Invaders or SPIN (Abstract). The consensus sequences are over 96% identical over their entire length (2.9 kb) in the genomes of murine rodents (Abstract). Pace hypothesizes the high sequence identity is due to the horizontal gene transfer across divergent species (Abstract). However, Pace generates no mutants of SPIN, nor does Pace functionally characterize any of the transposases.
Li et al. (Proceedings of the National Academy of Sciences 110.6 (2013): E478-E487) teaches an active version of red flour beetle Tribolium castaneum SPIN transposase as well as another transposase of the Buster family called TcBuster (Abstract). Li generates mutants of TcBuster (page E482, right column, TcBusterCO Transposase Mutation Results in Increased Transposition in Yeast and Mammalian Cells). Li also teaches several mutants of SPIN (page E479, left column, Results, Resurrection of a SPIN transposon; Supplementary Table S2)., but each of the mutants has less activity than SPINON (Table S2, Activity column). Li specifically teaches the SPINON mutant M8 containing the amino acid substitution M220T, which is one of the claimed amino acid substitutions, but this mutant has less activity than SEQ ID NO: 1 (SPINON).
Hyperactive variants of the Sleeping Beauty and piggyBac transposases are taught by the prior art: see the Abstract of Baus et al. (Molecular Therapy 12.6 (2005): 1148-1156) and the Abstract of Yusa et al. (Proceedings of the National Academy of Sciences 108.4 (2011): 1531-1536), respectively. However, SPIN transposases differ from both Sleeping Beauty and piggyBac transposases: Li teaches that both TcBuster and SPIN belong to the Buster family of hAT transposases and have different target site selection patterns with respect to mammalian genome features than piggyBac and Sleeping Beauty (page E479, left column, paragraph 3).
Hyperactive variants of TcBuster have also been identified. For example, Largaespada et al. (WO 2018/112415 A1; cited in IDS filed on 3/7/2023) teaches mutants of TcBuster with increased transposition efficiency (Largaespada claim 1 and Tables 2-3). However, TcBuster and SPIN are still sequence-divergent transposases: see the phylogenetic tree of Fig. 1 of Arensburger et al. (Genetics 188.1 (2011): 45-57), which shows SPIN transposases in one branch of the tree, separate from TcBuster1.
Given the above analysis, the person of ordinary skill in the art would not have recognized, as of the effective filing date of the claimed invention, that the inventors had possession of the claimed genus of mutant SPIN transposases having increased transposition efficiency in comparison to SEQ ID NO: 1. The person of ordinary skill in the art would also not have recognized that the inventors had possession of the claimed genus of fusion transposase mutants.
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 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 20-21, 23, 28, and 45 are rejected under 35 U.S.C. 103 as being unpatentable over Li et al. (Proceedings of the National Academy of Sciences 110.6 (2013): E478-E487) in view of Largaespada et al. (WO 2018/112415 A1; cited in IDS filed on 3/7/2023).
Regarding claims 20-21, 23, and 45, Li teaches an active version of red flour beetle Tribolium castaneum SPIN transposase as well as another transposase of the Buster family called TcBuster (Abstract). The amino acid translation of the DNA sequence of SPINON (Table S1) is identical to the instant SEQ ID NO: 1. See OA Appendix A for the sequence alignment. Li also teaches several mutants of SPIN (page E479, left column, Results, Resurrection of a SPIN transposon; Supplementary Table S2). Li specifically teaches the SPINON mutant M8 containing the amino acid substitution M220T, which is one of the claimed amino acid substitutions.
Li does not teach that the SPINON is fused to a TALE domain.
Largaespada teaches a fusion protein of TcBuster with a TALE domain (Largaespada claims 25 and 33). Largaespada teaches that TALE domains can be designed to target specific DNA sequences ([0093]).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to fuse LI’s SPINON transposase or any of LI’s functional SPINON mutants with a TALE domain per the teaching of Largaespada in order to target the transposase to specific DNA sequences. The person of ordinary skill in the art would have had a reasonable expectation of success given that both TcBuster and SPINON are both from the Buster subfamily of hAT transposases (Li Abstract).
Regarding claim 28, Li teaches mutants of SPINON including a mutant M8 comprising the amino acid substitution M220T (Table S2).
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.
Claims 20-21, 23, 28, and 45 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 7-11 of U.S. Patent No. 11,278,570 (hereafter ‘570) in view of Li et al. (Proceedings of the National Academy of Sciences 110.6 (2013): E478-E487).
Claims 7-11 of ‘570 are drawn to a fusion transposase comprising a TcBuster transposase sequence and one or more of a DNA sequence specific binding domain and an additional Nuclear Localization Signal sequence. Claim 8 of ‘570 recites that the DNA sequence specific binding domain comprises a TALE domain, zinc finger domain, AAV Rep DNA-binding domain, or any combination thereof.
Claims 7-11 of ‘570 do not recite that the transposase is a SPIN transposase with at least 70% identity to full-length SEQ ID NO: 1.
Regarding claims 20-21, 23, and 45, Li teaches an active version of red flour beetle Tribolium castaneum SPIN transposase as well as another transposase of the Buster family called TcBuster (Abstract). Fig. 5 of Li demonstrates that TcBuster and SPINON have different insertion profiles on the human genome. SEQ ID NO: 1 of the instant application is identical to the amino acid translation of the DNA sequence of SPINON (Table S1). See OA Appendix A for the sequence alignment. Li also teaches several functional mutants of SPIN (page E479, left column, Results, Resurrection of a SPIN transposon; Supplementary Table S2). Li specifically teaches the SPINON mutant M8 containing the amino acid substitution M220T, which is one of the claimed amino acid substitutions.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to replace the TcBuster sequence with Li’s SPINON. or any of Li’s functional mutant SPINON transposases in order to develop another genetic engineering tool for gene editing. The person of ordinary skill in the art would have had a reasonable expectation of success in replacing TcBuster with SPINON.
Regarding claim 28, Li teaches functional mutants of SPINON including a mutant M8 comprising the amino acid substitutions M220T (Table S2).
Claims 20-21, 23, 28, and 45 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 11,111,483 (hereafter ‘483) in view of Li et al. (Proceedings of the National Academy of Sciences 110.6 (2013): E478-E487).
Claims 1-11 of ‘483 are drawn to a fusion transposase comprising a TcBuster transposase amino acid sequence and a DNA sequence specific binding domain. Claim 2 of ‘483 recites the DNA sequence specific binding domain comprising a TALE domain, zinc finger domain, AAV Rep DNA-binding domain, or any combination thereof. Claim 3 of ‘483 recites the DNA sequence specific binding domain comprises a TALE domain.
Claims 1-11 of ‘483 do not recite that the transposase is a SPIN transposase with at least 70% identity to full-length SEQ ID NO: 1.
Regarding claims 20-21, 23, and 45, Li teaches an active version of red flour beetle Tribolium castaneum SPIN transposase as well as another transposase of the Buster family called TcBuster (Abstract). Fig. 5 of Li demonstrates that TcBuster and SPINON have different insertion profiles on the human genome. SEQ ID NO: 1 of the instant application is identical to the amino acid translation of the DNA sequence of SPINON (Table S1). See OA Appendix A for the sequence alignment. Li also teaches several functional mutants of SPIN (page E479, left column, Results, Resurrection of a SPIN transposon; Supplementary Table S2). Li specifically teaches the SPINON mutant M8 containing the amino acid substitution M220T, which is one of the claimed amino acid substitutions.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to replace the TcBuster sequence with Li’s SPINON. or any of Li’s mutant SPINON transposases in order to develop another genetic engineering tool for gene editing. The person of ordinary skill in the art would have had a reasonable expectation of success in replacing TcBuster with SPINON.
Regarding claim 28, Li teaches mutants of SPINON including a mutant M8 comprising the amino acid substitutions M220T (Table S2).
Claims 20-21, 23, 28, and 45 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 6-10 of U.S. Patent No. 11,760,983 (hereafter ‘983) in view of Li et al. (Proceedings of the National Academy of Sciences 110.6 (2013): E478-E487).
Claims 6-10 of ‘983 are drawn to a fusion transposase comprising a TcBuster transposase sequence and a DNA sequence specific binding domain. Claim 7 of ‘983 recites that the DNA sequence specific binding domain comprises a TALE domain, zinc finger domain, an AAV Rep DNA-binding domain, or any combination thereof.
Claims 6-10 of ‘983 do not recite that the transposase is a SPIN transposase with at least 70% identity to full-length SEQ ID NO: 1.
Regarding claims 20-21, 23, and 45, Li teaches an active version of red flour beetle Tribolium castaneum SPIN transposase as well as another transposase of the Buster family called TcBuster (Abstract). Fig. 5 of Li demonstrates that TcBuster and SPINON have different insertion profiles on the human genome. SEQ ID NO: 1 of the instant application is identical to the amino acid translation of the DNA sequence of SPINON (Table S1). See OA Appendix A for the sequence alignment. Li also teaches several functional mutants of SPIN (page E479, left column, Results, Resurrection of a SPIN transposon; Supplementary Table S2). Li specifically teaches the SPINON mutant M8 containing the amino acid substitution M220T, which is one of the claimed amino acid substitutions.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to replace the TcBuster sequence with Li’s SPINON. or any of Li’s mutant SPINON transposases in order to develop another genetic engineering tool for gene editing. The person of ordinary skill in the art would have had a reasonable expectation of success in replacing TcBuster with SPINON.
Regarding claim 28, Li teaches mutants of SPINON including a mutant M8 comprising the amino acid substitutions M220T (Table S2).
Claims 20-21, 23, 28, and 45 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 12-14 of U.S. Patent No. 12,037,611 (hereafter ‘611) in view of Li et al. (Proceedings of the National Academy of Sciences 110.6 (2013): E478-E487).
Claims 12-14 of ‘611 are drawn to a fusion transposase comprising a TcBuster transposase sequence and a DNA sequence specific binding domain. Claim 13 of ‘611 recites that the DNA sequence specific binding domain comprises a TALE domain, zinc finger domain, an AAV Rep DNA-binding domain, or any combination thereof.
Claims 12-14 of ‘611 do not recite that the transposase is a SPIN transposase with at least 70% identity to full-length SEQ ID NO: 1.
Regarding claims 20-21, 23, and 45, Li teaches an active version of red flour beetle Tribolium castaneum SPIN transposase as well as another transposase of the Buster family called TcBuster (Abstract). Fig. 5 of Li demonstrates that TcBuster and SPINON have different insertion profiles on the human genome. SEQ ID NO: 1 of the instant application is identical to the amino acid translation of the DNA sequence of SPINON (Table S1). See OA Appendix A for the sequence alignment. Li also teaches several functional mutants of SPIN (page E479, left column, Results, Resurrection of a SPIN transposon; Supplementary Table S2). Li specifically teaches the SPINON mutant M8 containing the amino acid substitution M220T, which is one of the claimed amino acid substitutions.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to replace the TcBuster sequence with Li’s SPINON. or any of Li’s mutant SPINON transposases in order to develop another genetic engineering tool for gene editing. The person of ordinary skill in the art would have had a reasonable expectation of success in replacing TcBuster with SPINON.
Regarding claim 28, Li teaches mutants of SPINON including a mutant M8 comprising the amino acid substitutions M220T (Table S2).
Claims 20-21, 23, 28, and 45 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 13-15 of U.S. Patent No. 12,0097,220 (hereafter ‘220) in view of Li et al. (Proceedings of the National Academy of Sciences 110.6 (2013): E478-E487).
Claims 13-15 of ‘220 are drawn to a fusion transposase comprising a mutant TcBuster transposase and a DNA sequence specific binding domain. Claim 14 of ‘220 recites that the DNA sequence specific binding domain comprises a TALE domain, zinc finger domain, an AAV Rep DNA-binding domain, or any combination thereof. Claim 15 of ‘220 limits the DNA sequence specific binding domain to a TALE domain.
Claims 13-15 of ‘220 do not recite that the transposase is a SPIN transposase with at least 70% identity to full-length SEQ ID NO: 1.
Regarding claims 20-21, 23, and 45, Li teaches an active version of red flour beetle Tribolium castaneum SPIN transposase as well as another transposase of the Buster family called TcBuster (Abstract). Fig. 5 of Li demonstrates that TcBuster and SPINON have different insertion profiles on the human genome. SEQ ID NO: 1 of the instant application is identical to the amino acid translation of the DNA sequence of SPINON (Table S1). See OA Appendix A for the sequence alignment. Li also teaches several functional mutants of SPIN (page E479, left column, Results, Resurrection of a SPIN transposon; Supplementary Table S2). Li specifically teaches the SPINON mutant M8 containing the amino acid substitution M220T, which is one of the claimed amino acid substitutions.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to replace the TcBuster sequence with Li’s SPINON. or any of Li’s mutant SPINON transposases in order to develop another genetic engineering tool for gene editing. The person of ordinary skill in the art would have had a reasonable expectation of success in replacing TcBuster with SPINON.
Regarding claim 28, Li teaches mutants of SPINON including a mutant M8 comprising the amino acid substitutions M220T (Table S2).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CANDICE LEE SWIFT whose telephone number is (571)272-0177. The examiner can normally be reached M-F 8:00 AM-4:30 PM (Eastern).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Louise Humphrey can be reached at (571)272-5543. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657
/CANDICE LEE SWIFT/Examiner, Art Unit 1657
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