Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Claims
Claims 1-10 are pending. Claims 1-2 and 8-10 are under exam. Claims 3-7 are withdrawn pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species
WITHDRAWN OBJECTIONS AND REJECTIONS
Drawings
The application contained at least one color drawing or color photograph and was rejected for requiring a petition. The objection is withdrawn following Applicant’s submission of replacement black and white drawings.
Claim Rejections - 35 USC § 112
Claims 1-2, and 8-10 were rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as failing to set forth 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 1 and 8 were rejected for reciting that “the guide promotes sufficient strand invasion by the RNA motif to allow the complex to be active while also exhibiting increased cleavage specificity….;” "the less thermodynamically stable DNA-DNA interaction" or “wherein a majority of the bases in the modified CRISPR RNA guide's target-defining spacer region are DNA nucleotides.”
The rejection is withdrawn following cancellation of the unclear terms.
Claim Rejections - 35 USC § 103
Claims 1-2 and 8-10 were rejected under 35 U.S.C. 103 as being unpatentable over May et al (WO2016123230A1; Published Aug 4, 2016 (hereinafter "May", see PTO-892), in view of Hummel et al (US20170175140A1; Published June 22, 2017; hereinafter "Hummel", see PTO-892), further as evidenced by Klett et al (Proc Natl Acad Sci U S A.; Published 1968 Jul; Hereinafter “Klett”; See PTO-892).
The rejection is withdrawn following claim amendments.
NEW REJECTIONS NECESSITATED BY CLAIM AMENDMENTS
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 1-2 and 8-10 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as failing to set forth 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.
Claim 1 requires a chimeric CRISPR DNA-RNA guide strand having a target-defining spacer region comprising an interspersed mixture of both DNA nucleotides and RNA bases, wherein the mixture comprises interspersed DNA nucleotides and RNA bases that includes at least one DNA nucleotide and an RNA motif comprising at least one RNA base. The claim language does not specify how many DNA bases are present in the spacer region of the claimed chimeric DNA-RNA guide or what the structural basis is utilized to replace RNA with DNA or how many RNA are replaced by DNA. Additionally, it is unclear what is exactly implied by “interspersed” as used in the claim. Appropriate clarification is required.
Claims 2 and 8-10 are rejected for their dependency on claim 1. For the purpose of this office action, the claim is interpreted to read on crRNA comprising DNA nucleotides.
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.
Claims1-2 and 8-10 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 claim(s) 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 inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 requires a chimeric CRISPR DNA-RNA guide strand having a target-defining spacer region comprising an interspersed mixture of both DNA nucleotides and RNA bases, wherein the mixture comprises interspersed DNA nucleotides and RNA bases that includes at least one DNA nucleotide and an RNA motif comprising at least one RNA base. The claim language does not specify how many DNA bases are present in the spacer region of the claimed chimeric DNA-RNA guide or what the structural basis is utilized to replace RNA with DNA. For the purposes of this rejection, it is interpreted that RNA at any random position in the targeting region of the spacer is changed into DNA nucleotide.
It is first noted that the specification does not give any special definition of “interspersed.” In this case, interspersed is given its dictionary meaning, “here and there.” (See Marriam Webster Dictionary, See PTO-892). [0040] of instant specification indicated that “17 of 20 bases in the crRNA's target-defining spacer region swapped with DNA nucleotides.” As such this gives
20
C
17
=
1140 different polynucleotides. Further, instant specification at [0038] indicated that the invention is directed to “lowering R-loop Tm for improving NGEn (nucleic acid-guided endonucleases) specificity, which is accomplished by substituting positions in nucleic acid guides with other nucleotide types or analogs.” Further Figure 1 showed 2 nucleotides swapped with DNA molecules: nucleotide #2 and #6. As such it is submitted that the specification did not provide adequate support a target-defining spacer region with DNA and RNA nucleotides at any position in the crispr RNA rather only at the specified enumerated locations as depicted in Figure 1. Further it is also noted that the specification did not provide adequate support for a crispr RNA of any length of CRISPR polynucleotides with any Cas9 where the target-defining spacer region comprises an interspersed mixture of both DNA nucleotides and RNA bases as claimed. The specification used a 20 base pair target-defining spacer region. It is understood by a person of ordinary skill in the art that although 20 base pair is the optimal length of the target defining region especially for Cas9, depending on the purpose of gene editing, the target defining region can be vary from 17-20 bases long. (See Fu abstract, See PTO-892).
Additionally, the claims or the specification did not provide any structural basis or rule for a skilled artisan to determine where the nucleic acid had to be modified in order to lower R-loop Tm for improving NGEn specificity. The specification only enumerated only one guide sequence which comprised RNA nucleotide at position 2 and 6 of the spacer region. It is submitted that the enumeration of only one embodiment does not constitute written description of all species of the claimed polynucleotides.
The specification as filed does not provide sufficient evidence that Applicants
were in possession of the full scope of the claimed invention at the time of filing. It is however clear from the specification that use of a construct with RNA nucleotide at position 2 and 6 as enumerated in figure 1. However, there is no support in the specification for a method of genome editing using a chimeric CRISPR DNA-RNA guide strand having a target-defining spacer region comprising an interspersed mixture of both DNA nucleotides and RNA bases. Therefore, it remains that it is the examiner’s position that the full scope of the claimed invention was not disclosed as of the filing date of the instant specification.
Claims 2, and 8-10 inherit the deficiency due to their direct/indirect dependence on claim 1.
Claims 1-2 and 8-10 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 enablement requirement.
The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Applicant's specification is found enabling for a method of editing using a CRISPR guide comprising a spacer with a target defining region with RNA nucleotide at position 2 and 6 as enumerated in figure 1.
Applicant's specification is not found to be enabling for a method of gene editing using a chimeric CRISPR DNA-RNA guide strand having a target-defining spacer region comprising an interspersed mixture of both DNA nucleotides and RNA bases, wherein the mixture comprises interspersed DNA nucleotides and RNA bases that includes at least one DNA nucleotide and an RNA motif comprising at least one RNA base. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to carry out the method of the invention commensurate in scope with the current claims.
Analysis of whether a particular claim is supported by the disclosure in an application requires a determination of whether that disclosure, when filed, contained sufficient information regarding the subject matter of the claims as to enable one skilled in the pertinent art to make and use the claimed invention without undue or unreasonable experimentation. See Mineral Separation v. Hyde, 242 U.S. 261, 270 (1916). The key word is 'undue,' not experimentation.' " (Wands, 8 USPQ2d 1404). The factors to be considered in determining whether undue experimentation is required are summarized In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988). The factors to be considered in determining whether undue experimentation is required include: (1) the quantity of experimentation necessary, (2) the amount or direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims. While all these factors are considered, a sufficient number are discussed below so as to create a prima facie case.
Applicants' claims are directed to a method of gene editing using a chimeric CRISPR DNA-RNA guide strand having a target-defining spacer region comprising an interspersed mixture of both DNA nucleotides and RNA bases, wherein the mixture comprises interspersed DNA nucleotides and RNA bases that includes at least one DNA nucleotide and an RNA motif comprising at least one RNA base. The breadth of the claims includes a method of editing a genome using a crispr RNA polynucleotide of where the RNA polynucleotide also comprises DNA nucleotides.
The specification provides methods of genome editing using nucleotide substitutions for spacer-DNA enhancement for example, nucleotides 2 and 6 were the RNA nucleotides and the rest of the 20bp target defining spacer was DNA. (See FIG. 1)
The specification showed in vitro cleavage assays of on-target (from a sequence in the human VEGF-A gene commonly used as a specificity benchmark) and off-target substrates by ribonucleoprotein assemblies of a corresponding SpaDE melt-guide complexed with tracrRNA and purified S. pyogenes Cas9, and showed reduced relative activity on the off-target sequence that is cleaved when using the SpaDE melt-guide. (See [0044])
The specification also demonstrated that a Cas9 guide with DNA substitutions has reduced activity on mismatched targets. (See [0051])
The specification demonstrated that a melt-guide containing mostly DNA in spacer bases produced indel percentages above 25% on-target (70% gRNA's rate). Crucially, on an off-target where gRNA-induced mutations were detected, melt-guides' indel percentages fell below the no-guide negative control. (See [0064])
At the time of the invention a Class 2 CRISPR system comprising:
a single polynucleotide comprising a targeting region comprising deoxyribonucleic acid (DNA) and configured to hybridize with a target sequence in a nucleic acid;
an activating region adjacent to said targeting region comprising a ribonucleic acid (RNA); and
a site-directed polypeptide was known. (See May, claim 11; See PTO of 2/27/2025).
Further, May disclosed a targeting region that comprising DNA and RNA. (See May Figure 12 A-F). May further indicated that the “targeting region comprises a mixture of DNA and RNA” (See May p. 2, para 3) (discuss prior art). May further indicated that combinations of secondary structure, protein-nucleic acid interaction, and sequence conservation are used to inform the positioning of ribonucleotides within crD(R)NA, tracrD(R)NA and sgD(R)NA sequence. Multiple designs of crD(R)NA and tracrD(R)NA are tested with the understanding that different configurations may support different desired properties (i.e., activity, specificity, stability, etc.). (See May p. 57 last para). As such May outlined to need to optimize the position of RNA or DNA nucleotides within a crRNA for each sequence. Therefore, there was a recognized level of unpredictability with regards to position of RNA or DNA nucleotides in a crispr RNA.
Due to the lack of teachings in the art regarding position of RNA or DNA nucleotides in a crispr RNA, and the recognized unpredictability in the area of gene editing using a crispr RNA comprising DNA and RNA nucleotides, a large amount of guidance and teachings would be necessary in order to be enabling for methods of such.
Guidance and teachings provided by Applicants in the instant specification is limited to disclosure that the construct as described in FIG. 1 can be used to edit VEGF sequence in the genome. The Examiner acknowledges that the Office does not require the presence of working examples to be present in the disclosure of the invention (see MPEP §2164.02). However, in light of the state of the art, discussed above, which recognizes a high level of unpredictability in the field of genome editing using a RNA-DNA hybrid crRNA, and limited teachings with regards to position of DNA or RNA, the Office would require appropriate disclosure to support the contention that a CRISPR RNA comprising an interspersed mixture of both DNA nucleotides and RNA bases may be successfully employed in the methods of claims 1-2, 8-10. The amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). Thus, due to the high level of unpredictability in the art, the current specification would have to provide greater amounts of teachings and guidance directed to methods of carrying out the claimed invention.
Therefore, due to the sum of all the aforementioned factors, one of ordinary skill in the art, at the time the invention was made, would not expect success carrying out the claimed method of genome editing. Given that the art fails to recognize and Applicant has failed to demonstrate positions of RNA or DNA bases, the skilled artisan would be faced with the impermissible burden of undue experimentation in order to practice the claimed invention using any species of stem cell. Accordingly, claims 1-2 and 8-10 are deemed properly rejected.
MAINTAINED REJECTION
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 1-2 and 8-10 are rejected under 35 U.S.C. 103 as being unpatentable over May et al (WO2016123230A1; Published Aug 4, 2016 (hereinafter "May", see PTO-892 of 2/27/2025), in view of Hummel et al (US20170175140A1; Published June 22, 2017; hereinafter "Hummel", see PTO-892 of 2/27/2025), further as evidenced by Klett et al (Proc Natl Acad Sci U S A.; Published 1968 Jul; Hereinafter “Klett”; See PTO-892 of 2/27/2025).
The rejection has been updated in view of Applicant’s amendment.
May teaches a method of editing a target nucleic acid (See May claim 31) using a single polynucleotide comprising: (1) a targeting region comprising deoxyribonucleic acid (DNA); and (2) an activating region adjacent to said targeting region comprising ribonucleic acid (RNA); wherein said single polynucleotide is for use with a Class 2 CRISPR system such as Cas9 (See May claims 1 and 9). Further, May teaches use of a domain that confers additional activity such as DNA repair activity or a nuclease activity along with the Class 2 CRISPR system. (See May, p. 15, 1st paragraph). FIGURE 1A of May taught polynucleotides for use in a Type II CRISPR system, where the targeting region comprises DNA and RNA nucleotides. May taught that the term "targeting region" refers to a region of a polynucleotide comprising DNA, or a mixture of DNA and RNA that is complementary to a sequence in a target nucleic acid. This reads on the claimed guide strand having a target-defining spacer region comprising an interspersed mixture of both DNA nucleotides and RNA bases, wherein the mixture comprises interspersed DNA nucleotides and RNA bases that includes at least one DNA nucleotide and an RNA motif comprising at least one RNA base.
May does not specifically teach co-transfection of exonucleases as required by claim 1. However, it is known that exonucleases are type of nucleases that promote DNA-repair activity, as evidenced by Klett (See Klett, p.1, paragraph 2). May does not teach coadministration of an exonuclease as required by the claim.
Hummel teaches that exonucleases can be coadministered with Class 2 CRISPR system to promote DNA repair. (See Hummel [0005]). It is noted for the sake of completeness that the claimed co-administration of exonucleases was not taught by the original provisional application 62/425,041 filed on Nov. 21, 2016. Therefore, this feature is not entitled to the priority date of Nov. 21, 2016 and is awarded the priority date of Nov. 21, 2017. As such all elements of the claim would have been obvious to a person of ordinary skill in the art, prior to the filing dates of instant application, in view of teachings of May as evidenced by Klett, p. 943, 1st paragraph, further in view of Hummel.
The person would have been motivated to co-administer exonucleases in view of teachings of May to administer a domain that confers additional activity such as DNA repair activity or a nuclease activity along with the Class 2 CRISPR system and would have had reasonable expectation of success to promote DNA repair by coadministering exonucleases as required by the claim.
The skilled artisan would also have had a reasonable expectation of success in
combining the teachings of May and Hummel because each of these teachings are directed to compositions and methods of editing a genome.
Regarding claim 2: The teachings of May and Hummel are set forth above. Figures 11B-11E of May shows a single guide D(R)NA wherein the targeting region comprises mixture of DNA and RNA. The targeting region in May reads on the spacer as claimed. (See May, p. 34, paragraph 2). It is specifically pointed out that Figure 11E shows a single guide D(R)NA wherein the targeting region comprises a mixture of DNA and RNA and the 5' stem, the 3' stem, and the loop comprise DNA. May did not specifically teach that the concentration of DNA bases in the targeting region of the spacer region in CRISPR RNA is between 50-100% as required by the amended claims. However, absent any teaching of criticality by the Applicant concerning the inoculum concentration, it would be prima facie obvious that one of ordinary skill in the art would recognize this as a result effective variable whose concentration is a matter of routine optimization. Differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such parameter is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (see MPEP 2144.05).
It is noted that Figures 11B-E of May only teach a Type V CRISPR system (which does not include Cas9) for use with the gRNA format wherein the targeting region comprises DNA, the 5' stem comprises DNA, and the loop and 3' stem comprise RNA. However, as indicated above, claims 1 and 9 of May teaches a method of editing a target nucleic acid (See May claim 31) using a single polynucleotide comprising: (1) a targeting region comprising deoxyribonucleic acid (DNA); and (2) an activating region adjacent to said targeting region comprising ribonucleic acid (RNA); wherein said single polynucleotide is for use with a Class 2 CRISPR system such as Cas9.
As such all elements of the claim would have been obvious to a person of ordinary skill in the art, prior to the filing dates of instant application, in view of teachings of May, further in view of Hummel.
The person would have been motivated to modify 50-less than 100% of nucleotides in the targeting region of crispr RNA to DNA nucleotides in view of teachings of May. Further the person would have been motivated to co-administer exonucleases in view of teachings of May and Hummel to administer a domain that confers additional activity such as DNA repair activity or a nuclease activity along with the Class 2 CRISPR system and would have had reasonable expectation of success to promote DNA repair by coadministering exonucleases as required by the claim.
The skilled artisan would also have had a reasonable expectation of success in
combining the teachings of May and Hummel because each of these teachings are directed to compositions and methods of editing a genome.
Regarding claims 8-9: May teaches “a method for reducing off-target modification using a Class 2 CRISPR system comprising: contacting a target nucleic acid molecule having a target sequence with: a first polynucleotide comprising (i) a targeting region comprising deoxyribonucleic acid (DNA) and configured to hybridize with a target sequence in a nucleic acid and (ii) an activating region adjacent to said targeting region comprising ribonucleic acid (RNA); providing a second polynucleotide comprising a sequence that is complementary to a sequence in said activating region of said first polynucleotide and a site-directed polypeptide, wherein the first and second polynucleotides form a complex with the site-directed polypeptide and wherein said target nucleic acid molecule is cleaved or edited at the target sequence more preferentially than at other sequences in the target nucleic acid, thereby reducing off-target modification.” (See May p. 5, paragraphs 2-3). The term “reducing off-target modification using a Class 2 CRISPR system comprising” as recited in May reads on the claimed “generating a complex comprising Cas9, trans-activating CRISPR RNA, and a chimeric CRISPR RNA.” The “a second polynucleotide comprising a sequence that is complementary to a sequence in said activating region of said first polynucleotide and a site-directed polypeptide” as recited in May reads on the claimed “genome editing.”
May did not specifically teach that the concentration of DNA bases in the targeting region of the spacer region in CRISPR RNA is between 50-100% as required by the amended claims. However, absent any teaching of criticality by the Applicant concerning the inoculum concentration, it would be prima facie obvious that one of ordinary skill in the art would recognize this as a result effective variable whose concentration is a matter of routine optimization. Differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such parameter is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (see MPEP 2144.05).
May does not teach coadministration of an exonuclease as required by the claim. As indicated above, Hummel teaches that exonucleases can be coadministered with Class 2 CRISPR system to promote DNA repair. (See Hummel [0005]).
As such all elements of the claim would have been obvious to a person of ordinary skill in the art, prior to the filing dates of instant application, in view of teachings of May, further in view of Hummel.
The person would have been motivated to reduce off-target modification using a Class 2 CRISPR system (such as Cas9) by administering a guide RNA comprising DNA nucleotides in the spacer region. The person would also be motivated to co-administer exonucleases in view of teachings of May and Hummel to administer a domain that confers additional activity such as DNA repair activity or a nuclease activity along with the Class 2 CRISPR system and would have had reasonable expectation of success to promote DNA repair by coadministering exonucleases as required by the claim.
The skilled artisan would also have had a reasonable expectation of success in combining the teachings of May and Hummel because each of these teachings are directed to compositions and methods of editing a genome.
Regarding claim 10: As indicated above, May teaches reduction of off-target effects by administering a Class 2 CRISPR system comprising a first polynucleotide comprising (i) a targeting region comprising deoxyribonucleic acid (DNA) and configured to hybridize with a target sequence in a nucleic acid and (ii) an activating region adjacent to said targeting region comprising ribonucleic acid (RNA). Further May indicates that the term "activating region" refers to a portion of a polynucleotide comprising RNA, or DNA, or a mixture of DNA and RNA that interacts, or is capable of associating, or binding with a site-directed polypeptide. (See May, p. 17, paragraph 2). May further indicates that a site-directed polypeptide can be a Cas9 protein. (See May, p. 3, paragraph 1).
May does not teach coadministration of an exonuclease as required by the claim. As indicated above, Hummel teaches that exonucleases can be coadministered with Class 2 CRISPR system to promote DNA repair. (See Hummel [0005]).
As such all elements of the claim would have been obvious to a person of ordinary skill in the art, prior to the filing dates of instant application, in view of teachings of May, further in view of Hummel.
The person would have been motivated to reduce off-target modification using a Class 2 CRISPR system (such as Cas9) by administering a guide RNA comprising DNA nucleotides in the spacer region and RNA in the targeting region as taught by May. The person would also be motivated to co-administer exonucleases in view of teachings of May and Hummel to administer a domain that confers additional activity such as DNA repair activity or a nuclease activity along with the Class 2 CRISPR system and would have had reasonable expectation of success to promote DNA repair by coadministering exonucleases as required by the claim.
Conclusion
No claim is free or art.
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 JAGAMYA VIJAYARAGHAVAN whose telephone number is (703)756-5934. The examiner can normally be reached 9:00a-5:00p.
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/JAGAMYA NMN VIJAYARAGHAVAN/ Examiner, Art Unit 1633
/EVELYN Y PYLA/ Primary Examiner, Art Unit 1633