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 .
The Applicants’ Amendment to the Claims filed on 10/15/2025 is entered.
Claims 1-23, 25-26, and 28-29 are cancelled.
Claims 24, 27, and 30-33 are pending and under examination.
Priority
This US 17/823,685 filed on 08/31/2022 is a DIV of 14/767,068 filed on 10/21/2015 (now US Patent 11,466,306) which is a 371 of PCT/JP2013/074107 filed on 09/06/2013 which claims foreign priority benefit of JAPAN 2013-026310 filed on 02/14/2013 and JAPAN 2013-143282 filed on 07/09/2013.
Terminal Disclaimer
The terminal disclaimer filed on 10/15/2025 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of US Patent 11,466,306 has been reviewed and is accepted. The terminal disclaimer has been recorded.
Accordingly, the NSDP rejection over US Patent 11,466,306 is withdrawn.
Response to Amendment
The rejection of claims 24, 27, and 30-33 under 35 U.S.C. 112(b) is withdrawn in view of the Applicants’ Amendment to the Claims filed on 10/15/2025.
The rejection of claims 24, 27, and 30-33 under 35 U.S.C.103 as being unpatentable over Zhang et al (“Finding regulatory sequence” The International Journal of Biochemistry & Cell Biology Vol 35, No 1, January 2003, pages 95-103) in view of Kim et al (“A zinc finger protein array for the visual detection of specific DNA sequences for diagnostic applications” Nucleic Acids Res 2010 Dec 5 Vol 39 No.5, pages 1-9) is withdrawn in view of the Applicants’ Amendment to the Claims filed on 10/15/2025.
Claim Rejections - 35 USC § 103– new grounds
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.
KSR, 550 U.S. at 418, 82 USPQ2d at 1396. Exemplary rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) "Obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching. suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention."
Currently amended claims 24, 27, and 30-33 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al (“Finding regulatory sequence” The International Journal of Biochemistry & Cell Biology Vol 35, No 1, January 2003, pages 95-103) in view of Kim et al (“A zinc finger protein array for the visual detection of specific DNA sequences for diagnostic applications” Nucleic Acids Res 2010 Dec 5 Vol 39 No.5, pages 1-9), in view of either of the references of Doudna et al (US 2014/0068797 A1, with US priority to at least to US Provisional 61/757,640 filed 01/28/2013; of record) or Dahlem et al (“Simple Methods for Generating and Detecting Locus-Specific Mutations Induced with TALENs in the Zebrafish Genome” PLOS Genetics published August 16, 2012).
Regarding base claims 24 and 31, Zhang et al disclose a method for isolating a specific genomic region while maintaining the interaction of genomic DNA and molecules interacting therewith, the method comprising the following steps I to III just below. For example, regarding step I: Zhang et al disclose fragmenting genomic DNA isolated from cells in a state where the interaction of the genomic DNA and molecules interacting therewith is maintained using crosslinking of proteins to DNA (See FIG 1 & 2 just below). Regarding step II, Zhang et al disclose bringing the genomic DNA fragmented in step I into contact with an exogenous molecule which binds to a specific endogenous DNA sequence in the genomic DNA, without prior denaturation of the genomic DNA, wherein the exogenous molecule is brought into contact with the fragmented genomic DNA and immobilized or subsequently immobilized onto a carrier wherein the genomic DNA does not have a recognition sequence of an exogenous molecule inserted therein. (See FIG 1 & 2 just below). Regarding step III, Zhang et al disclose harvesting a genomic DNA fragment bound to an exogenous molecule. (See FIG 1 & 2 just below).
Regarding claims 27 and 32, Zhang et al discloses a step of performing a crosslinking treatment for maintaining the interaction of genomic DNA and molecules interacting therewith. (See FIG 1 & 2 just below).
Regarding claims 30 and 33, Zhang et al discloses a method for analyzing the molecular mechanisms of genome functions, the method comprising: isolating a specific genomic region and identifying molecules interacting with the genomic DNA of the isolated specific genomic region by one or more selected from the group consisting of mass spectrometry, immunoblot, ELISA, nucleotide sequence analysis, microarray analysis and PCR. (See FIG 1 & 2 just below).
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However, Zhang et al differs from the present claims because they do not specify the exogenous molecule being a TAL effector protein, or a complex of an inactive Cas9 protein and a guide RNA (gRNA).
Kim et al disclose a system for binding DNA using a zinc finger binding array. (See FIG 1 just below). Kim et al do not require heterologous DNA inserted into target sites. Kim et al recite: “Using these predefined modules, six zinc finger domains have the theoretical capacity to bind 18 base pairs of contiguous DNA, which would be sufficient to describe a unique site within all known genomes”. (See Introduction). Kim et al continues that: “Engineered zinc finger domains have been fused to effectors such as transcriptional regulatory domains and nucleases for gene regulation and genome modification”. (See Introduction).
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However, although Kim et al disclose a system for binding DNA using zinc finger binding array, regarding the presently amended claims which delete the alternative of zinc finger protein from the base claims 24 and 31, Kim et al does not specify the exogenous molecule being a TAL effector protein, or a complex of an inactive Cas9 protein and a guide RNA (gRNA).
Doudna et al disclose the use of a complex of inactive Cas9 protein and a gRNA as the DNA binding agent to bind a specific region of the genomic DNA. Such Cas9/gRNA complex does not require a recognition sequence inserted into the genome but rather such complex recognizes the endogenous genomic sequence. Doudna et al teach methods of using the Cas9 and guide RNA in several different applications. Doudna et al teach that a catalytically dead Cas9, lacking endonuclease activity, when co- expressed with a guide RNA, generates a DNA recognition complex [0240-0241 of '640 Provisional]. Doudna et al state that this nuclease inactive Cas9 may be used in cases where one wishes to reduce the likelihood of double stranded breaks. (See para 0241).
Dahlem et al disclose synthetic DNA-binding nuclease proteins called TALENs (see Abstract). Dahlem et al disclose that TALENs with “very high target sequence specificities can be easily generated” stated that “a TALEN that uniquely recognizes a specific pre-determined locus in the zebrafish genome can be generated within days” (see Abstract).
The level of skill in the art was high before the effective filing date of the presently claimed invention.
Substituting a TALEN protein OR a dCas9/sgRNA complex for the zinc finger binding protein of Kim et al was a design step well within the grasp of a person of ordinary skill in the relevant art before the effective filing date of the presently claimed invention as evidenced by either of Doudna et al (dCas9/sgRNA complex) or Dahlen et al (TALEN protein).
One of ordinary skill in the art would have been motivated to combine the elements of Zhang et al and Kim et al, and Doudna et al specifically to use a system for binding DNA using a DNA-binding protein binding array of such as shown in Kim et al but using a complex of an inactive Cas9/gRNA complex of Doudna et al or TALEN protein of Dahlen et al so as not to require heterologous DNA inserted into target sites for examining native genomic DNA for rationales of Zhang et al and Kim et al. Further, Kim et al provides a rationale for such a system to not require heterologous DNA inserted into target sites. Kim et al recite: “Using these predefined modules, six zinc finger domains have the theoretical capacity to bind 18 base pairs of contiguous DNA, which would be sufficient to describe a unique site within all known genomes”. (See Introduction). Kim et al continues that: “Engineered zinc finger domains have been fused to effectors such as transcriptional regulatory domains and nucleases for gene regulation and genome modification”. (See Introduction).
It would have been obvious for one of ordinary skill in the art to substitute a complex of an inactive Cas9/gRNA or TALEN protein for the zinc finger binding protein in the DNA-binding protein array of Kim et al because dCas9/sgRNA complexes and TALEN proteins were known in the art as DNA-binding proteins which bind genomic DNA fragments but do not require heterologous DNA inserted into target sites similar to zinc binding proteins. (See Doudna et al and Dahlen et al). Doudna et al state that this nuclease inactive Cas9 may be used in cases where one wishes to reduce the likelihood of double stranded breaks. (See para 0241). Dahlem et al disclose that TALENs with “very high target sequence specificities can be easily generated” stated that “a TALEN that uniquely recognizes a specific pre-determined locus in the zebrafish genome can be generated within days” (see Abstract).
Further, the cited references are in the same field of study of binding genomic DNA.
In view of the high skill level in the art before the effective filing date it is considered that one of ordinary skill in the art would have had a reasonable expectation of success to combine the elements of Zhang et al, Kim et al, and Doudna et al to arrive at the presently claimed invention.
Thus the claims as a whole are rendered obvious over the combination of cited references.
Response to Arguments
The applicants’ response filed on 10/15/2025 has been fully considered but is unpersuasive as it may pertain to this new grounds of rejection. The applicants argue that claims 24 and 31 are amended to delete a the alternative of a zinc finger protein. This argument is persuasive for the previous rejection made over Zhang in view of Kim which has been withdrawn. The present new grounds of rejection is made in view of Doudna et al which meets the limitation of a complex of an inactive Cas9 protein and a gRNA in place of a zinc finger binding protein.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CATHERINE S HIBBERT whose telephone number is (571)270-3053. The examiner can normally be reached M-F 8:00-5:00.
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CATHERINE S. HIBBERT
Primary Examiner
Art Unit 1658
/CATHERINE S HIBBERT/Primary Examiner, Art Unit 1658