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 .
Election/Restrictions
Applicant’s election without traverse of Group I, D581R, I926R, and V1030G; a Cas12i2 polypeptide comprising the amino acid sequence of SEQ ID NO: 227, exon 3, a target sequence of SEQ ID NO: 337, a spacer sequence of SEQ ID NO: 416, a direct repeat sequence of SEQ ID NO: 10, and an RNA guide comprising the nucleotide sequence of SEQ ID NO: 355 in the reply filed on 8/6/26 is acknowledged.
Claims 64, 70, and 71 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 8/6/26.
Claim Objections
Claims 4 and 14 are objected to because of the following informalities:
In claim 4, line 1 “the gene editing gene editing system” should read as “the gene editing system”. Appropriate correction is required.
Claim 14 appears to inadvertently recite an additional hyphen after “30” and “36”. Appropriate correction is required.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 67 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kurosawa et al. (Biochemical and Biophysical Research Communications 337 (2005) 1012–1018).
Kurosawa et al. teach a cell comprising a mutant TTR. Kurosawa et al. teach that six siRNAs were designed to target the sequence containing the single mutated nucleotide of the mutant Val30Met TTR coding region and were transfected into COS-7 cells (page 1013). Therefore, the claim is anticipated by Kurosawa et al. It is noted that the claim does not require anything that is recited as optional.
Claim(s) 67 and 72 is/are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Bogorad et al. (WO 2018/007871 A1).
Bogorad et al. teaches: [0053] In some embodiments, the method further comprises introducing into the cell one guide ribonucleic acid (gRNA) and a polynucleotide donor template comprising at least a portion of the wild-type TTR gene. In some embodiments, the method further comprises introducing into the cell one guide ribonucleic acid (gRNA) and a polynucleotide donor template comprising at least a portion of a codon optimized or modified TTR gene. In some embodiments, the one or more DNA endonucleases is one or more Cas9 or Cpf1 (Cpf1 also known as Cas12a) endonucleases that effect one single-strand break (SSB) or double-strand break (DSB) at a locus within or near the TTR gene (or codon optimized or modified TTR gene) or other DNA sequences that encode regulatory elements of the TTR gene that facilitates insertion of a new sequence from the polynucleotide donor template into the chromosomal DNA at the locus that results in a permanent insertion or correction of a part of the chromosomal DNA of the TTR gene or other DNA sequences that encode regulatory elements of the TTR gene proximal to the locus. In some embodiments, the gRNA comprises a spacer sequence that is complementary to a segment of the locus. In some embodiments, proximal means nucleotides both upstream and downstream of the locus.
Bogorad et al. teaches: [00595] Regions of the TTR gene were scanned for target sites. Each area was scanned for a protospacer adjacent motif (PAM) having the sequence TTN. gRNA 22 bp spacer sequences corresponding to the PAM were identified.
Bogorad et al. teaches that the CRISPR gene editing system comprises short repeat sequences that are interspaced with spacers and appear as direct repeat followed by spacer sequence ([00194], lines 1-6 and [00199], lines 5-9) (instant claim 13).
Bogorad et al. teaches delivery to cells and therefore the resultant cell meets the instant limitations of claim 67.
Therefore, the claim is anticipated by Bogorad et al.
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.
Claims 1-6, 9-11, 13-15, 17, 18, 23, 30, 33, 60, 62, 63, 67, and 72 are rejected under 35 U.S.C. 103 as being unpatentable over Bogorad et al. (WO 2018/007871 A1), in view of Cheng et al. (US 2020/0063126 A1), and Li (Pub No. CN112195164A, pub date 01/08/2021).
Bogorad et al. teaches: Materials and methods for treating a patient with Transthyretin Amyloidosis, both ex vivo and in vivo, are provided, and materials and methods for modulating the expression, function, or activity of a Transthyretin (TTR) gene in a cell by genome editing are provided (abstract).
Bogorad et al. teaches: [0053] In some embodiments, the method further comprises introducing into the cell one guide ribonucleic acid (gRNA) and a polynucleotide donor template comprising at least a portion of the wild-type TTR gene. In some embodiments, the method further comprises introducing into the cell one guide ribonucleic acid (gRNA) and a polynucleotide donor template comprising at least a portion of a codon optimized or modified TTR gene. In some embodiments, the one or more DNA endonucleases is one or more Cas9 or Cpf1 (Cpf1 also known as Cas12a) endonucleases that effect one single-strand break (SSB) or double-strand break (DSB) at a locus within or near the TTR gene (or codon optimized or modified TTR gene) or other DNA sequences that encode regulatory elements of the TTR gene that facilitates insertion of a new sequence from the polynucleotide donor template into the chromosomal DNA at the locus that results in a permanent insertion or correction of a part of the chromosomal DNA of the TTR gene or other DNA sequences that encode regulatory elements of the TTR gene proximal to the locus. In some embodiments, the gRNA comprises a spacer sequence that is complementary to a segment of the locus. In some embodiments, proximal means nucleotides both upstream and downstream of the locus (instant claim 23).
Bogorad et al. teaches: [0048] In some embodiments, the one or more deoxyribonucleic acid (DNA) endonuclease is one or more protein or polypeptide. In some embodiments, the one or more deoxyribonucleic acid (DNA) endonuclease is one or more polynucleotide encoding the one or more DNA endonuclease. In some embodiments, the one or more deoxyribonucleic acid (DNA) endonuclease is one or more ribonucleic acid (RNA) encoding the one or more DNA endonuclease. In some embodiments, the one or more ribonucleic acid (RNA) is one or more chemically modified RNA.
Bogorad et al. teaches: [00215] In some embodiments, the site-directed polypeptide comprises a modified form of a wild-type exemplary site-directed polypeptide. In some embodiments, the modified form of the wild- type exemplary site-directed polypeptide comprises a mutation that reduces the nucleic acid-cleaving activity of the site-directed polypeptide. In some embodiments, the modified form of the wild- type exemplary site-directed polypeptide has less than 90%, less than 80%, less than 70%, less than 60%, less than 50%, less than 40%, less than 30%, less than 20%, less than 10%, less than 5%, or less than 1 % of the nucleic acid-cleaving activity of the wild-type exemplary site-directed polypeptide (e.g., Cas9 from S. pyogenes, supra). In some embodiments, the modified form of the site-directed polypeptide has no substantial nucleic acid-cleaving activity. When a site-directed polypeptide is a modified form that has no substantial nucleic acid-cleaving activity, it is referred to herein as "enzymatically inactive."
Bogorad teaches that the polypeptide of Cas endonuclease comprises mutations that modify the nuclease activity ([00215], lines 1-5) and these mutations can include one or more amino acid substitutions ([00216], lines 21-23).
Bogorad teaches that the gene-editing comprises introducing guide RNA or gRNA into a cell ([0054], lines 1-2). Bogorad teaches that the gene editing system comprises a nucleic acid (i.e. referring to the second nucleic acid) or a nucleotide sequence encoding a genome-targeting nucleic acid or guide RNA ([00374], lines 1-2).
Bogorad teaches that one or more gRNAs for editing the TTR gene comprise a spacer sequence selected from nucleic acid sequences for targeting the TTR gene (i.e. the spacer sequence is specific to a target sequence within the TTR gene) ([0080], lines 1-4) (instant claim 1).
Bogorad teaches that the target nucleic acid in a CRISPR system refers to as a protospacer adjacent motif (PAM) that is essential to facilitate binding of an endonuclease to the target nucleic acid ([00197], lines 10-13) (instant claim 1).
Bogorad et al. teaches: [00194] A spacer sequence is located at the 5' or 3' end of the crRNA (instant claim 1).
Bogorad et al. teaches: [00595] Regions of the TTR gene were scanned for target sites. Each area was scanned for a protospacer adjacent motif (PAM) having the sequence TTN. gRNA 22 bp spacer sequences corresponding to the PAM were identified (instant claim 1).
Bogorad teaches that Cpf1 (i.e. an endonuclease of Cas12 family of endonucleases) utilizes a T-rich PAM motif such that Cpf1 or Cas12a-gRNA complexes efficiently cleave target DNA preceded by a short T-rich PAM ([00199], lines 10-11).
Bogorad teaches that CRISPR/Cas system comprising the spacer sequence is designed to hybridize to a target nucleic acid that is located 5’ of a PAM ([00246]), and for targeting or correcting TTR gene using CRISPR/Cas or Cas12a/Cpf1 system, a gRNA comprises a spacer sequence that is complementary to the segment of the locus ([00525], [00527]). Bogorad also teaches that target sites of the TTR gene corresponding to a PAM comprises the sequence motif TTN ([00595], lines 1-2).
Although Bogorad et al. teach a gene editing system for genetic editing of TTR comprising an RNA guide comprising a spacer sequence specific to a target sequence within a TTR gene, the target sequence being adjacent to a PAM comprising 5’-TTN-3’, which is located 5’ to the target sequence and a Cas12 family endonuclease polypeptide as part of the CRISPR complex in editing TTR gene (as described above), Bogorad et al. does not specifically teach a Cas12i2 polypeptide comprising an amino acid sequence that is at least 95% identical to instant SEQ ID NO: 222 and comprises one or more mutations relative to SEQ ID NO: 222.
However, one of ordinary skill in the art would have considered the teachings of Cheng et al. as both references are analogous prior arts pertaining to compositions for CRISPR gene editing system.
Cheng et al. teaches: novel systems, methods, and compositions for the manipulation of nucleic acids in a targeted fashion. The disclosure describes non-naturally occurring, engineered CRISPR systems, components, and methods for targeted modification of nucleic acids such as DNA. Each system includes one or more protein components and one or more nucleic acid components that together target nucleic acids (Abstract).
Cheng et al. teaches: [0016] In some embodiments of any of the systems described herein, the Type V-I CRISPR-Cas effector protein includes or consists of an amino acid sequence that is at least 80% (e.g., 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) identical to the amino acid sequence of Cas12i1 (SEQ ID NO: 3) or Cas12i2 (SEQ ID NO: 5). In some embodiments, the Type V-I CRISPR-Cas effector protein is Cas12i1 (SEQ ID NO: 3) or Cas12i2 (SEQ ID NO: 5) (identical to instant SEQ ID NO: 222) (instant claim 1).
Therefore, it would have been obvious to select the Cas12i2 sequence of Cheng et al. as the Cas sequence for the gene editing system of Bogorad et al. as a matter of design choice, as each were known Cas enzymes that edit target sequences.
Cheng et al. teaches that type V-I CRISPR-Cas effector protein comprises one or more amino acid substitution within at least one of the RuvC domains ([0018]). Cheng also teaches that Cas12i2 can recognize a PAM and the target nucleic acid sequence comprising PAM with a 5′-TTN-3′ motif sequence ([0017]) which is located to the left of the target sequence (i.e. 5’ to the target sequence) ([0164], lines 1-3). Therefore, it would have been obvious for the Cas12i2 sequence to have one or more mutations as this was a known design element as taught by Cheng et al. for Cas12i2(instant claim 1).
The resultant cell comprising the mutated TTR gene anticipates instant claim 67.
Cheng et al. teach that the CRISPR-Cas system comprises a type V-I Cas effector protein (i.e. Cas12i2) or a nucleic acid encoding the type V-I Cas effector protein, wherein the type V-I CRISPR-Cas effector protein is capable of binding to a type V-I RNA guide ([0012], lines 8-11).
Cheng et al. teaches that the CRISPR-Cas system comprises a nucleic acid (referring to the first nucleic acid) encoding a type V-I CRISPR-Cas effector protein (Cas12i2) in a viral vector ([0045], lines 1-3) and [0046]).
Cheng et al. teaches that the selective benefit of using recombinant AAV vector and size limit of type V-I CRISPR-Cas effector protein allow greater versatility in packaging Cas12i2 endonucleases and RNA guides for efficient cell-type specific expression [0313].
Bogorad et al. teach: [0067] In some embodiments, the Cas9 or Cpf1 mRNA, and gRNA are either each formulated separately into lipid nanoparticles or all co-formulated into a lipid nanoparticle (instant claims 6 and 30).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to simply substitute i) the Cas endonuclease of Cas12 family protein of Bogorad et al. for Cas12i2 (i.e., a Cas endonuclease of Cas12 family protein) of Cheng et al., ii) the first nucleic acid encoding Cas12a of Bogorad et al. for the nucleic acid encoding Cas12i2 of Cheng et al., and iii) the vector encoding Cpf1 of Bogorad et al. for the vector encoding Cas12i2 of Cheng et al. A person of ordinary skill in the art would have had a reasonable expectation of success because Cheng et al. teach a CRISPR-Cas system comprising nucleic acid sequence encoding Cas12i2 capable of binding RNA guide for correcting a target gene and a viral vector as a delivery vehicle with a benefit of versatile packaging of the Cas12i2 protein and efficient expression of the target sequence. A person of ordinary skill in the art would also have had a reasonable expectation of success because Cheng et al. teaches the gene editing system with CRISPR Cas12i2 included in a viral vector and wherein Cas12i2 comprises the SEQ ID NO: 222 with one or more amino acid substitution. Therefore, since Bogorad et al. teaches employing a CRISPR-Cas gene-editing system for treating TTR amyloidosis and Cheng et al. teaches Cas12i2 based modification of target nucleic acid using a viral vector, simply substituting the nucleic acid encoding Cas endonuclease in delivery vehicle of Bogorad et al. for the nucleic acid encoding the Cas12i2 in a viral vector of Cheng et al. would have resulted in the predictable outcome of success.
Bogorad teaches that TTR gene editing comprises introducing gRNAs or a polynucleotide (i.e. target sequence) into the cell, comprising segments of the TTR gene that is part of exon 1, 2, 3 or 4 ([0051], lines 1-3 and [0052], lines 1-8) (instant claim 9).
Bogorad et al. teaches the sequence of instant SEQ ID NO: 337 by indicating that gRNAs editing the TTR gene comprise a spacer sequence selected from a group of nucleic acid sequences related to the TTR gene target ([0080], lines 1-4, and [0095]; claim 49, SEQ ID NOS: 1-8669). The TTR target sequence of Bogorad i.e. SEQ ID NO: 337 has a 100% sequence identity of the instantly claimed spacer sequence with SEQ ID NO: 416 (SEQ ID NOS: 1-8669). Therefore, Bogorad teaches the spacer sequence or SEQ ID NO: 416 with 100% identity (instant claims 10, 11, and 14).
Bogorad et al. teaches that the CRISPR gene editing system comprises short repeat sequences that are interspaced with spacers and appear as direct repeat followed by spacer sequence ([00194], lines 1-6 and [00199], lines 5-9) (instant claim 13).
Bogorad does not teach the use of a direct repeat sequence that comprises SEQ ID NO: 10 (instant claims 15 and 17).
However, Cheng et al. teaches the SEQ ID NO: 10 with 100% identity and explains that the type V-I CRISPR system (having Cas12i2 effector protein) comprises direct repeats within the gRNA or RNA guide ([0059], line 7-8, SEQ ID NO: 101, and [0111], lines 14-15; see attached SEQ ID search result). Therefore, when utilizing Cas12i2, incorporation of a direct repeat sequence of instant SEQ ID NO: 10 is a known and obvious selection that is a matter of design choice (instant claim 14).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to simply substitute the direct repeat of Bogorad et al. for direct repeat sequence of Cheng et al. A person of ordinary skill in the art would have had a reasonable expectation of success because Cheng et al. teaches composition of CRISPR-Cas system comprising Cas12i2 and gRNA for correcting a target gene. Since Bogorad et al. teaches employing CRISPR-Cas gene-editing system for treating TTR amyloidosis having the direct repeat interspersed with spacers and Cheng et al. teaches composition of gRNA such as specific direct repeat sequences or SEQ ID NO: 10, simply substituting the gRNA direct repeat of Bogorad et al. for the direct repeat sequence of Cheng et al. would have resulted in the predictable outcome of success.
Cheng et al. teaches that the gene editing system comprises nucleic acid (referring to the first nucleic acid) encoding Cas12i2 effector protein (as discussed above) and a nucleic acid (referring to a second nucleic acid) encoding an RNA guide located in the viral vector ([0045], 0046]). Cheng also teaches that the Cas12i2 effector protein and RNA guides can be packaged into one or more viral vectors ([0311], lines 10-11).
Regarding claim 33, Bogorad et al. teaches method for editing a TTR gene in a cell by gene editing system ([0016], lines 1-2). In this regard, the applicable teachings of Bogorad in view of Cheng are described above as applied to claims 1 and 9.
Regarding claim 60 part (i), Bogorad et al. teaches about TTR gene-editing system and composition comprising the Cas12a of Cas12 family polypeptide as discussed above. In this regard, the applicable teachings of Bogorad et al. in view of Cheng et al. are described above as applied to claim 1(i).
Regarding claim 60 part (ii) Bogorad teaches about nucleic acid (or second nucleic acid) encoding RNA guide and further limitations as the applicable teachings are described above as applied to claims 1(ii), 9 and 11.
Regarding claim 60 part (iii) Bogorad teaches that the method of TTR gene editing comprises at least a portion of the target TTR gene including regulatory elements (upstream promoter/enhancer and downstream polyA signal) and the template DNA can be fragments of TTR exons or introns or a combination thereof ([0052], lines 1-8). Bogorad teaches that (c) the donor template comprises a codon optimized or modified TTR gene (i.e. a variant of the TTR target site) ([0053], lines 5-6). Bogorad teaches that the donor region comprises the corrected sequence with small or large flanking homology arms (i.e. referring to the segments homologous to the (a) upstream and (b) downstream of TTR gene) or the template can comprise additional sequences flanked by the homologous regions ([00123], lines 1-7). Bogorad teaches that the homologous donor template comprises sequences that are homologous to sequences flanking the target nucleic acid cleavage site (i.e. the upstream and downstream homologous segments of the TTR target site) ([00189], lines 10-11).
Regarding instant claims 62 and 63, Bogorad et al. discloses kits and pharmaceutical formulation for the gene editing system ([00447]). Bogorad teaches that a kit comprises one or more of the genome-targeting nucleic acids, polynucleotides encoding genome-targeting nucleic acid (i.e. gRNA), site-directed polypeptide or endonuclease, polynucleotide encoding the endonuclease and other components necessary to carry out the gene editing process ([00447], lines 1-4). Bogorad teaches that gRNAs are formulated with pharmaceutically acceptable excipients depending on the mode of administration and dosage form ([00456], lines 1-4).
Regarding claim 72(i), the applicable teachings of Bogorad in view of Cheng are described above as applied to claim 1(i).
Regarding claim 72(ii) Bogorad teaches that one or more gRNAs for editing the TTR gene comprise a spacer sequence selected from nucleic acid sequences for targeting the TTR gene (i.e. the spacer sequence is specific to a target sequence within the TTR gene) ([0080], lines 1-4). Bogorad teaches that the target nucleic acid in a CRISPR system refers to as a protospacer adjacent motif (PAM) that is essential to facilitate binding of an endonuclease to the target nucleic acid ([00197], lines 10-13). Bogorad teaches that the endonuclease utilizes a T-rich PAM motif such that Cpf1/Cas12a-gRNA complexes efficiently cleave target DNA preceded by a short T-rich PAM ([00199], lines 10-11). Bogorad teaches that CRISPR/Cas system comprising the spacer sequence is designed to hybridize to a target nucleic acid that is located 5’ of a PAM ([00246], lines 1-2). Bogorad also teaches that target sites of the TTR gene corresponding to a PAM comprises the sequence motif TTN ([00595], lines 1-2). Bogorad teaches that the CRISPR gene editing system comprises short repeat sequences that are interspaced with spacers and appear as direct repeat followed by spacer sequence ([00194], lines 1-6 and [00199], lines 5-9).
Bogorad et al. does not teach specific mutations in the Cas12i2 polypeptide.
However, one of ordinary skill in the art would have considered the teachings of Li as both references are analogous prior arts pertaining to the method and composition of CRISPR gene editing system.
Li is drawn to an invention providing a method of engineering Cas nucleases (including Cas12i) to increase CRISPR enzymatic activity (Abstract). Li teaches that engineered Cas12i effector protein can have improved activity such as target binding, double strand cleavage activity and/or gene-editing activity (pg. 35, paragraph 2, lines 1-2). The engineered Cas12i (referring to Cas12i2) comprises one or more mutations that increases the flexibility of a flexible region in a wild type nuclease (i.e. Cas12i2) comprising the flexible regions (i.e. the positions of amino acid substitution) of amino acid residues 925-929 (i.e. including I926 referring to the wild type amino acid ‘I’ at position 926) (pg. 35, paragraph 3, lines 1-5). Li teaches that one or more mutations comprise a substitution of a hydrophobic amino acid residue in the flexible region (as mentioned above), wherein the hydrophobic amino acid residue is selected from the group consisting of L, I, V, C, Y, F and W (referring ‘I’ at position 926) and the hydrophobic amino acid residue (such as ‘I’) is substituted with amino acid residues from a group including ‘R’ (rendering I926R substitution mutation) (pg. 35, paragraph 3, lines 10-16).
Li et al. teaches extensive options for insertion of mutations into Cas12i2 for improved activity. Selection of a specific mutation or combination of mutations is considered to be routine in the art and a matter of design choice. The general parameters of such design were known, as evidenced by Li et al. (instant claims 2-5).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to mutate the Cas12i2 rendered obvious by Bogorad in view of Cheng with an I926R mutation, as described by Li. A person of ordinary skill in the art would have had a reasonable expectation of success because Bogorad in view of Cheng teaches a CRISPR-Cas system comprising Type V-I or Cas12i2 for correcting a target gene and Li teaches specific amino acid substitution at specific positions of the Cas12i2 polypeptide for modulating nuclease activity. A person of ordinary skill in the art would have been motivated to do so in order to mutate the Cas endonuclease with amino acid substitution at certain positions for gene editing with improved specificity and robustness. Therefore, since Cheng teaches the use of Cas12i2 polypeptide and Li teaches mutating a Cas12i2 polypeptide at specific amino acid residues, mutating the Cas12i2 rendered obvious by Cheng with an I926R mutation, as described by Li, would have resulted in the predictable outcome of success (instant claims 2 and 3).
Claims 1-6, 9-11, 13-15, 17, 18, 23, 30, 33, 60, 62, 63, 67, and 72 are rejected under 35 U.S.C. 103 as being unpatentable over Bogorad et al. (WO 2018/007871 A1), in view of Cheng et al. (US 2020/0063126 A1), and Li (Pub No. CN112195164A, pub date 01/08/2021), as set forth above, further in view of Chong et al. (WO 2021/202800 A1).
The applied reference of Chong et al. has a common assignee with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
Chong et al. teach variant Cas12i2 polypeptides and teach that the mutation can be D581R, I926R, and/or V1030G. Chong et al. teach that the mutated forms exhibits increased binary complex formation, RNA guide binding activity and/or RNA guide binding specificity.
Therefore, it would have been obvious to select these specific mutations as a matter of design choice given that they were known to have the benefits of Chong et al.
Conclusion
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/AMY ROSE HUDSON/Primary Examiner, Art Unit 1636
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