DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Application Status
The Amendments and Remarks filed 28 August 2026 in response to the Office Action dated 28 August 2026 are acknowledged and have been entered. Claim 58 is newly added. Claims 41-43 and 45-58 are pending and being examined on the merits.
The rejections set forth in the Office action dated 28 August 2026 are withdrawn in view of applicant’s claim amendments and a new rejection is set forth below.
Priority
The instant application is a CON of application 16/851,360 filed 04/17/2020, which is a CON of application 16/441,209 filed 06/14/2019, which is a CON of application 14/319,530 filed 06/30/2014, which is a CON of PCT US2014/040868 filed on 06/04/2014, which claims priority to US provisional 61/830,787 filed 06/04/2013.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 58 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 58 recites “The method of claim 14 wherein the gRNA is a tracrRNA-crRNA fusion.” However, claim 14 has been canceled. Claims 1-40, including claim 14, are no longer pending in the application. Because claim 14 has been canceled, claim 58 does not presently depend from an existing claim whose subject matter is incorporated into and further limited by claim 58. Applicants may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 103
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 41-43 and 45-58 are rejected under 35 U.S.C. 103 as being unpatentable over Doudna et al. (US20140068797 A1, 01/28/2013, cited on the information disclosure statement filed 04/20/2020) in view of SenGupta (SenGupta et al., Proc. Natl. Acad. Sci. USA 93:8496-8501 (1996)).
Regarding claim 41, Doudna teaches a method of modulating expression of a target nucleic acid in a cell by providing to the cell a DNA-targeting RNA, also referred to as a guide RNA, and an enzymatically inactive or nuclease-null Cas9 protein, wherein the DNA-targeting RNA directs the Cas9 protein to a complementary target DNA sequence and transcription of the target nucleic acid is modulated [0130, 0136-0137, 0163, 0409-0412, 0775]. Doudna further teaches that the DNA-targeting RNA may comprise an additional segment at either the 5′ or 3′ end that comprises a modification or sequence providing a binding site for proteins that act on DNA, expressly including transcriptional activators, transcriptional repressors, DNA methyltransferases, DNA demethylases, histone acetyltransferases, and histone deacetylases [0133, 0385, 0425, 0443]. Thus, Doudna expressly teaches modifying the guide RNA itself so that the guide RNA contains a binding site for a transcriptional regulator. Doudna further teaches transcriptional regulation using catalytically inactive Cas9 and teaches association of transcriptional regulatory domains with the Cas9 targeting system, including transcriptional activator proteins fused to catalytically inactive Cas9 [0415-0419]. Thus, Doudna teaches that transcriptional activators or repressors may be associated with an RNA-guided Cas9 targeting system to regulate transcription of a target nucleic acid.
Doudna does not expressly exemplify an embodiment wherein a separate transcriptional regulator is directly tethered to the guide RNA through an RNA-binding interaction and wherein the RNA-recruited transcriptional regulator remains functional to modulate transcription at the target nucleic acid
SenGupta teaches a known and experimentally demonstrated RNA-mediated transcriptional-regulator recruitment system. Specifically, SenGupta teaches a yeast three-hybrid system wherein binding of a bifunctional RNA to two hybrid proteins activates transcription of a reporter gene in vivo [Abstract]. SenGupta teaches that the system employs a known RNA-binding protein to tether an RNA containing the cognate binding site and further provides the RNA with a binding site for a second RNA-binding protein, wherein the second RNA-binding protein is fused to a transcriptional activation domain [p. 8498, col. 1, ¶4]. SenGupta further teaches that interaction of the RNA with both RNA-binding domains results in the transcriptional activation domain being positioned at the promoter and thereby results in transcriptional activation of the reporter gene [p. 8498, col. 1, ¶4]. SenGupta teaches use of the bacteriophage MS2 coat protein as an RNA-binding protein and teaches that the MS2 coat protein recognizes a 21-nucleotide RNA stem-loop with high affinity [p. 8498, col. 1, ¶4]. The MS2 coat protein was joined to the LexA DNA-binding protein such that the MS2-containing hybrid protein tethered the RNA to a DNA locus [p. 8498, col. 1, ¶4]. The same hybrid RNA further contained a binding site for a second RNA-binding protein that was fused to a transcriptional activation domain [p. 8498, col. 1, ¶4]. SenGupta further depicts and explains this arrangement in Figure 2A. A first hybrid protein containing a DNA-binding domain and a first RNA-binding domain localizes to the promoter of a reporter gene, while a second hybrid protein contains a transcriptional activation domain and a second RNA-binding domain. The hybrid RNA contains recognition sites for both RNA-binding proteins and thereby links the two hybrid proteins together, with formation of the tripartite complex resulting in detectable expression of the reporter gene [p. 8498, col. 2, ¶1; Fig. 2A]. SenGupta further teaches an embodiment wherein IRP1 was fused to the Gal4 transcriptional activation domain and the hybrid RNA contained two MS2 coat-protein-binding sites and an iron-response element recognized by IRP1 [p. 8498, col. 2, ¶2]. Thus, SenGupta teaches a transcriptional activation domain fused to an RNA-binding protein that is directly recruited to a cognate binding sequence contained within an RNA molecule. Importantly, SenGupta experimentally demonstrates that the RNA-recruited transcriptional regulator remains functional. Cells containing the LexA-MS2 coat-protein hybrid, the activation-domain-IRP1 hybrid, and the hybrid RNA exhibited readily detectable β-galactosidase activity [p. 8499, col. 1, ¶2]. SenGupta concludes from these experiments that the hybrid RNA must be capable of simultaneously binding both hybrid proteins and that the resulting RNA-protein complex can trigger transcription [p. 8499, col. 1, ¶2]. SenGupta further teaches that elimination of either the MS2 coat protein or its RNA-binding sites severely reduced transcriptional activation; specific recognition of the IRE by IRP1 was required; IRP1 was essential; and the activation domain itself was required because IRP1 alone was inactive [p. 8499, col. 2, ¶1]. SenGupta therefore provides experimental evidence that a transcriptional activation domain fused to an RNA-binding protein can bind a cognate RNA sequence and remain functionally capable of activating transcription following RNA-mediated recruitment. SenGupta additionally teaches the same principle using a different RNA-protein pair by teaching a hybrid RNA comprising MS2 sites and the HIV TAR RNA sequence was combined with a hybrid protein containing Tat linked to a transcriptional activation domain, and transcriptional activation occurred when the cognate TAR/Tat pair was present [p. 8499, col. 2, ¶2]. Table 1 further shows that the matched TAR-MS2/activation-domain-Tat system produced 30 units of β-galactosidase activity and the matched IRE-MS2/activation-domain-IRP1 system produced 110 units, whereas mismatched or incomplete combinations produced only approximately 0.4-0.5 units [p. 8499, col. 2, ¶2; Table 1].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to implement the transcriptional-regulator-binding site expressly taught by Doudna on the guide RNA using the known RNA-binding-domain/transcriptional-regulator recruitment architecture taught by SenGupta. Doudna expressly directs the artisan to place an additional sequence on the DNA-targeting RNA that provides a binding site for proteins acting on DNA, including transcriptional activators and transcriptional repressors. SenGupta teaches a known and experimentally validated way of accomplishing such RNA-mediated recruitment, namely, by providing an RNA-binding sequence recognized by an RNA-binding protein fused to a transcriptional activation domain. One of ordinary skill in the art would have been motivated to make the modification because it would have implemented the protein-binding function that Doudna expressly teaches for the additional guide-RNA segment using an established RNA-protein recruitment technique. The guide RNA would continue to perform its disclosed function of associating with nuclease-null Cas9 and directing the complex to complementary target DNA, while the additional RNA-binding segment would perform the additional function expressly contemplated by Doudna of recruiting a transcriptional activator or repressor. The proposed modification would not change the principle of operation of Doudna. Doudna's guide RNA would continue to associate with nuclease-null Cas9 and hybridize to its complementary target sequence. The additional RNA segment would perform precisely the protein-binding function that Doudna expressly proposes. SenGupta merely teaches an established mechanism for carrying out that expressly disclosed protein-binding function.
One of ordinary skill in the art also would have had a reasonable expectation of success because SenGupta experimentally demonstrates that an RNA-binding-protein/transcriptional-activation-domain fusion can bind a cognate RNA recognition sequence while retaining transcriptional activation. SenGupta additionally teaches that stable RNA structures recognized by MS2 coat protein, IRP1, and Tat can form in unnatural RNA contexts, remain recognized by their cognate proteins, and coexist in a single RNA molecule in vivo [p. 8500, col. 2, ¶1]. Thus, the art provided an affirmative basis for expecting an RNA recognition element incorporated into another RNA scaffold, such as Doudna's guide RNA, to remain functional for protein recruitment. Upon binding of the transcriptional-regulator fusion to the corresponding binding sequence carried by the guide RNA, the transcriptional regulator would be directly tethered to the guide RNA through the RNA/RNA-binding-protein interaction. When the same guide RNA associates with nuclease-null Cas9 and hybridizes to the target nucleic acid, the guide-RNA-bound transcriptional regulator and nuclease-null Cas9 would thereby co-localize at the target nucleic acid. SenGupta establishes that a transcriptional activation domain recruited through such an RNA-protein interaction remains capable of modulating transcription.
Regarding claim 42, Doudna teaches that a subject method involves introducing into a host cell (or a population of host cells) one or more nucleic acids comprising nucleotide sequences encoding a DNA-targeting RNA and/or a variant Cas9 site-directed polypeptide, thereby teaching the introduction of a plurality of guide RNAs with a nuclease null Cas9 [0469, 0422].
Regarding claim 43, Doudna teaches a CRISPRi system that can be used to repress multiple target genes simultaneously and uses a catalytically dead Cas9, lacking endonuclease activity, co-expressed with a guide RNA, to generate a DNA recognition complex that can specifically interfere with transcriptional elongation, RNA polymerase binding, or transcription factor binding [0726]. Doudna teaches that CRISPRi can be used to repress multiple target genes simultaneously [0726].
Regarding claim 45, Doudna teaches introducing into a cell (or a population of cells) one or more nucleic acids comprising nucleotide sequences encoding a site-directed modifying polypeptide (e.g., a naturally occurring Cas9; a modified, i.e., mutated or variant, Cas9; a chimeric Cas9; etc.). [0276, 0329].
Regarding claim 46-47, Doudna teaches that suitable hosts include human cells [324-328].
Regarding claims 48-50 and 52-54, Doudna teaches that the DNA-targeting RNA" or "DNA targeting RNA polynucleotide" (also referred to herein as a "guide RNA" or "gRNA") can have a length of from about 12 nucleotides to about 100 nucleotides [0130, 0428].
Regarding claim 51, Doudna teaches the target DNA may be, for example, naked DNA in vitro, chromosomal DNA in cells in vitro, chromosomal DNA in cells in vivo, etc. [0254].
Regarding claim 55, the teachings of Doudna are discussed above as applied to claims 42 and 43.
Regarding claims 56-57, Doudna teaches where the DNA-targeting RNAs can be differently recognized by dCas9 proteins from different bacteria, such as S. pyogenes [0445].
Regarding claim 58, Doudna teaches a tracrRNA-crRNA fusion [Fig. 9; 0137].
Response to Arguments
Applicant's arguments filed 28 August 2026 regarding the rejection of the claims over 35 U.S.C. 103 have been fully considered but they are moot because the new ground of rejection does not rely on Doudna alone or matter specifically challenged in the argument. Doudna expressly directs the skilled artisan to provide the DNA-targeting RNA with an additional segment that functions as a binding site for proteins acting on DNA and expressly identifies transcriptional activators and transcriptional repressors among the proteins to be bound. SenGupta supplies the implementation that Applicant contends is absent from Doudna. SenGupta teaches an RNA-binding protein fused to a transcriptional activation domain and a cognate RNA binding sequence. Binding of the activation-domain fusion to the RNA results in formation of a functional transcriptional activation complex and reporter-gene transcription. Accordingly, the rejection does not require one of ordinary skill to invent an unspecified binding mechanism. Doudna instructs the artisan to place a transcriptional-regulator binding site on the RNA, and SenGupta teaches a known RNA-binding-domain/transcriptional-activation-domain system for accomplishing that function.
Applicant argues that, if Doudna's binding site already binds a transcriptional modulator by a non-covalent interaction, the artisan would have had no reason to alter that mechanism. This argument is based upon a narrower interpretation of “directly tethered” than is warranted by the claim language when read in light of the Specification. The Specification itself uses “tethered” terminology for an architecture in which an RNA aptamer/stem-loop on the guide RNA binds an RNA-binding protein fused to a transcriptional regulatory domain. Thus, the claimed tether does not require replacement of non-covalent RNA-protein binding with a covalent RNA-protein bond. Rather, direct binding of an RNA-binding-domain/transcriptional-regulator fusion to its cognate RNA site is within the tethering architecture contemplated by the disclosure. The modification proposed by the rejection is therefore not conversion of Doudna's system from a non-covalent mechanism to an unrelated covalent mechanism. It is implementation of Doudna's expressly disclosed transcriptional-regulator binding site using the known RNA-binding-domain/transcriptional-activation-domain architecture demonstrated by SenGupta.
Applicant argues under MPEP §2143.01(VI) and In re Ratti that the proposed modification would change Doudna's principle of operation. The argument is not persuasive. Doudna's principle of operation remains unchanged. A DNA-targeting RNA associates with nuclease-null Cas9 and directs the complex to a complementary target DNA sequence. Doudna expressly contemplates that the same DNA-targeting RNA may contain an additional segment that binds proteins acting on DNA, including transcriptional activators and repressors. Implementation of that expressly contemplated binding site using SenGupta's known RNA-binding-domain/transcriptional-activation-domain architecture leaves the RNA-guided Cas9 targeting mechanism intact. The guide RNA continues to associate with nuclease-null Cas9 and hybridize to its target DNA. The added RNA-binding segment performs precisely the additional protein-recruitment function contemplated by Doudna. Accordingly, the proposed combination does not require the substantial reconstruction or abandonment of the operating principle prohibited by In re Ratti.
Applicant argues that Doudna merely identifies a binding site and does not expressly say where or when binding occurs, what happens after binding, or that the bound regulator is carried to target DNA. The Examiner agrees that the cited passages of Doudna need not be read as an experimental demonstration of the entire claimed RNA-recruitment architecture. The present rejection therefore does not depend upon the proposition that Doudna alone experimentally established such localization. Instead, Doudna teaches three pertinent facts: (1) the DNA-targeting RNA guides the Cas9 complex to target DNA; (2) the DNA-targeting RNA may contain an additional binding site for transcriptional activators and repressors; and (3) RNA-associated site-directed modifying proteins can possess transcription-modulating activity whose site of action is determined by the DNA-targeting RNA. SenGupta supplies experimental evidence that a transcriptional activation domain fused to an RNA-binding protein can bind its cognate RNA and remain functional as a transcriptional activator. When Doudna's guide RNA simultaneously binds nuclease-null Cas9, hybridizes to target DNA, and carries the regulator-binding site expressly contemplated by Doudna, the regulator bound to that guide RNA is physically associated with the same RNA molecule localized at the target. No separate inherency proposition regarding a hypothetical Doudna protein is required.
Applicant argues that the prior Office Action lacked evidence establishing that direct tethering and non-covalent recruitment were known localization strategies or predictable substitutes. The present rejection does not rely upon that unsupported general proposition. SenGupta provides the missing evidence. SenGupta experimentally demonstrates RNA-mediated recruitment of a protein fused to a transcriptional activation domain and activation of transcription after formation of the RNA-mediated complex. Thus, the present rejection relies upon a specific prior-art implementation rather than a generalized assertion of predictable interchangeability. Furthermore, Doudna itself provides the reason to make the combination by expressly identifying transcriptional activators and transcriptional repressors as proteins for which the added guide-RNA segment may provide a binding site.
Applicant argues that Doudna provides no basis for expecting that modification of its guide RNA would continue to permit dCas9 targeting or that an RNA-bound transcriptional regulator would remain functional. The argument is not persuasive when the references are considered together. Doudna expressly contemplates adding the relevant protein-binding segment to the 5′ or 3′ end of the DNA-targeting RNA while maintaining the RNA's DNA-targeting and Cas9-associated functions. Thus, Doudna itself proposes the relevant modification to the RNA. SenGupta experimentally demonstrates that an RNA-binding protein fused to a transcriptional activation domain can bind an RNA while the activation domain remains functional and produces transcriptional activation. The combined references therefore provide affirmative evidence for both portions of the proposed system: Doudna for preservation of CRISPR targeting with an additional protein-binding RNA segment, and SenGupta for preservation of transcriptional activation following RNA-mediated recruitment of the activation-domain fusion. A reasonable expectation of success does not require absolute predictability or a guarantee of success.
Applicant argues that the prior statement that transcriptional activators or repressors bound to Doudna's guide RNA would “remain capable of their intended biological functions” constitutes an inherency position requiring proof that the result necessarily occurs. The present rejection does not rely upon inherency. The functionality of an RNA-recruited transcriptional activation domain is taught affirmatively by SenGupta. SenGupta demonstrates transcriptional activation resulting from binding of an RNA-binding-domain/transcriptional-activation-domain fusion to RNA. The Examiner therefore need not establish that every hypothetical transcriptional activator bound to every hypothetical Doudna RNA binding site necessarily remains functional. The question under §103 is whether the claimed arrangement as a whole would have been obvious to a person of ordinary skill in view of the combined teachings and whether such a person would have had a reasonable expectation of success. SenGupta provides affirmative evidence satisfying that inquiry.
Applicant argues that claim 41 requires not only tethering of the transcriptional regulator to the guide RNA but also that the transcriptional regulator actually modulate expression of the target nucleic acid. All limitations have been considered. The combination therefore provides both the structural relationship required by the claim and the claimed functional consequence of transcriptional modulation.
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 Langi, 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 §§ 706.02(1)(1) - 706.02(1)(3) 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-l.isp.
Claims 41-43 and 45-58 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 5, 8-9, 12-14, and 22 of U.S. Patent No. 8993233 (cited on the information disclosure statement filed 04/20/2020) in view of Doudna (US20140068797 A1, 01/28/2013, cited on the information disclosure statement filed 04/20/2020) and SenGupta (SenGupta et al., Proc. Natl. Acad. Sci. USA 93:8496-8501 (1996)) .
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claimed invention is obvious over the claims of the patent. The patented claims all the limitations of the instant claims except, wherein the guide RNA or plurality of guide RNAs is tethered, fused, connected or joined to the transcriptional regulator, wherein the cell is a human cell and wherein the guide RNA is about 100 nucleotides. The teachings of Doudna and SenGupta are discussed above.
It would have been obvious to one ordinary skilled in the art before the effective filing date of the claimed invention to modify the copending Application claims where the guide RNA as claimed is fused to a transcriptional regulator and wherein the Cas is a null Cas nuclease. One of ordinary skill would be motivated to make the modification given’s Doudna and SenGupta teachings that transcription can be modulated with the use of more than one DNA targeting RNA that is up to 100 nucleotides and that can be fused to a transcriptional activator or repressor. One or ordinary skill would have a reasonable expectation of success as both the patented claims, and each reference teach methods of modulation of gene expression.
For additional limitations of the instant claims, see the additional teachings of the patented claims. To the extent that there are limitations that are not provided for by the patented claims, the teachings of Doudna are discussed above. It would have been obvious to have modified the subject matter of the patented claims to arrive at the subject matter of the instant claims for substantially the same reasons as discussed above in view of the teachings of Doudna.
Claims 41-43 and 45-58 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-28 of U.S. Patent No. 8999641 (cited on the information disclosure statement filed 04/20/2020) in view of Doudna (US20140068797 A1, 01/28/2013, cited on the information disclosure statement filed 04/20/2020) and SenGupta (SenGupta et al., Proc. Natl. Acad. Sci. USA 93:8496-8501 (1996)).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claimed invention is obvious over the claims of the patent. The patent claims all the limitations of the instant claims except, wherein the guide RNA or plurality of guide RNAs is tethered, fused, connected or joined to the transcriptional regulator, wherein the cell is a human cell and wherein the guide RNA is about 100 nucleotides. The teachings of Doudna and SenGupta are discussed above.
It would have been obvious to one ordinary skilled in the art before the effective filing date of the claimed invention to modify the copending Application claims where the guide RNA as claimed is fused to a transcriptional regulator and wherein the Cas is a null Cas nuclease. One of ordinary skill would be motivated to make the modification given’s Doudna and SenGupta teachings that transcription can be modulated with the use of more than one DNA targeting RNA that is up to 100 nucleotides and that can be fused to a transcriptional activator or repressor. One or ordinary skill would have a reasonable expectation of success as both the patented claims, and each reference teach methods of modulation of gene expression.
For additional limitations of the instant claims, see the additional teachings of the patented claims. To the extent that there are limitations that are not provided for by the patented claims, the teachings of Doudna are discussed above. It would have been obvious to have modified the subject matter of the patented claims to arrive at the subject matter of the instant claims for substantially the same reasons as discussed above in view of the teachings of Doudna.
Claim 41-43 and 45-58 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 8932814B2 (cited on the information disclosure statement filed 04/20/2020) in view of Doudna (US20140068797 A1, 01/28/2013, cited on the information disclosure statement filed 04/20/2020) and SenGupta (SenGupta et al., Proc. Natl. Acad. Sci. USA 93:8496-8501 (1996)).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claimed invention is obvious over the claims of the patent. The patent claims all the limitations of the instant claims except, wherein the guide RNA or plurality of guide RNAs is tethered, fused, connected or joined to the transcriptional regulator, wherein the cell is a human cell and wherein the guide RNA is about 100 nucleotides. The teachings of Doudna and SenGupta are discussed above.
It would have been obvious to one ordinary skilled in the art before the effective filing date of the claimed invention to modify the copending Application claims where the guide RNA as claimed is fused to a transcriptional regulator and wherein the Cas is a null Cas nuclease. One of ordinary skill would be motivated to make the modification given’s Doudna and SenGupta teachings that transcription can be modulated with the use of more than one DNA targeting RNA that is up to 100 nucleotides and that can be fused to a transcriptional activator or repressor. One or ordinary skill would have a reasonable expectation of success as both the patented claims, and each reference teach methods of modulation of gene expression.
For additional limitations of the instant claims, see the additional teachings of the patented claims. To the extent that there are limitations that are not provided for by the patented claims, the teachings of Doudna are discussed above. It would have been obvious to have modified the subject matter of the patented claims to arrive at the subject matter of the instant claims for substantially the same reasons as discussed above in view of the teachings of Doudna.
Claims 41-43 and 45-58 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 8871445 (cited on the information disclosure statement filed 04/20/2020) in view of Doudna (US20140068797 A1, 01/28/2013, cited on the information disclosure statement filed 04/20/2020) and SenGupta (SenGupta et al., Proc. Natl. Acad. Sci. USA 93:8496-8501 (1996)).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claimed invention is obvious over the claims of the patent. The patent claims all the limitations of the instant claims except, wherein the guide RNA or plurality of guide RNAs is tethered, fused, connected or joined to the transcriptional regulator, wherein the cell is a human cell and wherein the guide RNA is about 100 nucleotides. The teachings of Doudna and SenGupta are discussed above.
It would have been obvious to one ordinary skilled in the art before the effective filing date of the claimed invention to modify the copending Application claims where the guide RNA as claimed is fused to a transcriptional regulator and wherein the Cas is a null Cas nuclease. One of ordinary skill would be motivated to make the modification given’s Doudna and SenGupta teachings that transcription can be modulated with the use of more than one DNA targeting RNA that is up to 100 nucleotides and that can be fused to a transcriptional activator or repressor. One or ordinary skill would have a reasonable expectation of success as both the patented claims, and each reference teach methods of modulation of gene expression.
For additional limitations of the instant claims, see the additional teachings of the patented claims. To the extent that there are limitations that are not provided for by the patented claims, the teachings of Doudna are discussed above. It would have been obvious to have modified the subject matter of the patented claims to arrive at the subject matter of the instant claims for substantially the same reasons as discussed above in view of the teachings of Doudna.
Claims 41-43 and 45-58 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 and 25 of copending Application No. 14/681510 in view of Doudna (US20140068797 A1, 01/28/2013, cited on the information disclosure statement filed 04/20/2020) and SenGupta (SenGupta et al., Proc. Natl. Acad. Sci. USA 93:8496-8501 (1996)). The instant application and the copending applicant have a common assignee.
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claimed invention is obvious over the claims of the copending Application. The copending Application claims all the limitations of the instant claims except, wherein the guide RNA or plurality of guide RNAs is tethered, fused, connected or joined to the transcriptional regulator, wherein the cell is a human cell and wherein the guide RNA is about 100 nucleotides. The teachings of Doudna and SenGupta are discussed above.
It would have been obvious to one ordinary skilled in the art before the effective filing date of the claimed invention to modify the copending Application claims where the guide RNA as claimed is fused to a transcriptional regulator and wherein the Cas is a null Cas nuclease. One of ordinary skill would be motivated to make the modification given’s Doudna and SenGupta teachings that transcription can be modulated with the use of more than one DNA targeting RNA that is up to 100 nucleotides and that can be fused to a transcriptional activator or repressor. One or ordinary skill would have a reasonable expectation of success as both the patented claims, and each reference teach methods of modulation of gene expression.
For additional limitations of the instant claims, see the additional teachings of the patented claims. To the extent that there are limitations that are not provided for by the patented claims, the teachings of Doudna are discussed above. It would have been obvious to have modified the subject matter of the patented claims to arrive at the subject matter of the instant claims for substantially the same reasons as discussed above in view of the teachings of Doudna.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 41-43 and 45-58 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over allowed claims 17-26 of U.S. Patent 11535863B2 in view of Doudna (US20140068797 A1, 01/28/2013, cited on the information disclosure statement filed 04/20/2020) and SenGupta (SenGupta et al., Proc. Natl. Acad. Sci. USA 93:8496-8501 (1996)). The instant application and the copending applicant have a common assignee.
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claimed invention is obvious over the claims of the patent. The patent claims all the limitations of the instant claims except, wherein the guide RNA or plurality of guide RNAs is tethered, fused, connected or joined to the transcriptional regulator, wherein the cell is a human cell and wherein the guide RNA is about 100 nucleotides. The teachings of Doudna and SenGupta are discussed above.
It would have been obvious to one ordinary skilled in the art before the effective filing date of the claimed invention to modify the copending Application claims where the guide RNA as claimed is fused to a transcriptional regulator and wherein the Cas is a null Cas nuclease. One of ordinary skill would be motivated to make the modification given’s Doudna and SenGupta teachings that transcription can be modulated with the use of more than one DNA targeting RNA that is up to 100 nucleotides and that can be fused to a transcriptional activator or repressor. One or ordinary skill would have a reasonable expectation of success as both the patented claims, and each reference teach methods of modulation of gene expression.
For additional limitations of the instant claims, see the additional teachings of the patented claims. To the extent that there are limitations that are not provided for by the patented claims, the teachings of Doudna are discussed above. It would have been obvious to have modified the subject matter of the patented claims to arrive at the subject matter of the instant claims for substantially the same reasons as discussed above in view of the teachings of Doudna.
Claims 41-43 and 45-58 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 13-14, and 25-35 of copending Application No. 14/319,530 in view of Doudna (US20140068797 A1, 01/28/2013, cited on the information disclosure statement filed 04/20/2020) and SenGupta (SenGupta et al., Proc. Natl. Acad. Sci. USA 93:8496-8501 (1996)). The instant application and the copending applicant have a common assignee.
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claimed invention is obvious over the claims of the copending Application. The copending Application claims all the limitations of the instant claims except, wherein the guide RNA or plurality of guide RNAs is tethered, fused, connected or joined to the transcriptional regulator, and wherein the Cas nuclease is a null Cas nuclease. The teachings of Doudna and SenGupta are discussed above.
It would have been obvious to one ordinary skilled in the art before the effective filing date of the claimed invention to modify the copending Application claims where the guide RNA as claimed is fused to a transcriptional regulator and wherein the Cas is a null Cas nuclease. One of ordinary skill would be motivated to make the modification given’s Doudna and SenGupta teachings that transcription can be modulated with the use of more than one DNA targeting RNA that is up to 100 nucleotides and that can be fused to a transcriptional activator or repressor. One or ordinary skill would have a reasonable expectation of success as both the patented claims, and each reference teach methods of modulation of gene expression.
For additional limitations of the instant claims, see the additional teachings of the patented claims. To the extent that there are limitations that are not provided for by the patented claims, the teachings of Doudna are discussed above. It would have been obvious to have modified the subject matter of the patented claims to arrive at the subject matter of the instant claims for substantially the same reasons as discussed above in view of the teachings of Doudna.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 41-43 and 45-58 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of US Patent 11981917 B2 in view of Doudna (US20140068797 A1, 01/28/2013, cited on the information disclosure statement filed 04/20/2020) and SenGupta (SenGupta et al., Proc. Natl. Acad. Sci. USA 93:8496-8501 (1996)). The instant application and the copending applicant have a common assignee.
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claimed invention is obvious over the claims of the patent. The patent claims all the limitations of the instant claims except wherein the guide RNA or plurality of guide RNAs is tethered, fused, connected or joined to a transcriptional regulator. The teachings of Doudna and SenGupta are discussed above.
It would have been obvious to have modified the subject matter of the patented claims to arrive at the subject matter of the instant claims for substantially the same reasons as discussed above in view of the teachings of these references. For additional limitations of the instant claims, see the additional teachings of the patented claims. To the extent that there are limitations that are not provided for by the patented claims, the teachings of Doudna are discussed above. It would have been obvious to have modified the subject matter of the patented claims to arrive at the subject matter of the instant claims for substantially the same reasons as discussed above in view of the teachings of Doudna.
Response to Arguments
Applicants argue that the patented or application claims are not obvious over Doudna and therefore, they are patentably distinct from the present claims. Applicants’ arguments have been considered and found not persuasive for the same reasons discussed above. Therefore, all nonstatutory double patenting rejections are maintained.
Conclusion
No claims are allowed.
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/TIFFANY NICOLE GROOMS/Examiner, Art Unit 1637
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