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
This Application is a National Stage entry under U.S.C. § 371 of PCT/US2020/018124 filed 02/13/2020.
Amendments to claims filed 10/14/2025 are hereby acknowledged. Claims 1, 6, 8-9, 23, 25-27, 37, 67, 77, 81-82, 109-110, 113-114, 130, 132, 134, 136, 146, 184, 188, 190-192, 194 and 202-203 are currently pending.
Claims 2-5, 7, 10-22, 24, 28-36, 38-66, 68-76, 78-80, 83-108, 111-112, 115-129, 131, 133, 135, 137-145, 147-183, 185-187, 189, 193, 195-201, and 204-205 are cancelled. Claims 1, 6, 8-9, 23, 25-27 and 130* are currently amended.
Claims 37, 67, 77, 81-82, 109-110, 113-114, 130*, 132, 134, 136, 146, 184, 188, 190-192, 194 and 202-203 are withdrawn from consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Inventions; Applicant elected without traverse of Invention group I (claims 1, 6, 8, 9, 23 and 25-27) and Species Q154S (claim 26) and Species Y147T + Q154S (claim 27) in the reply filed on 04/23/2025.
*Examiner interpreted claim 130 as being drawn to the same subject matter belonging to Invention Group I, therefore, claims 1, 6, 8, 9, 23, 25-27 and 130 are under examination in this office action.
Any objection or rejection not reiterated herein has been overcome by Applicant’s amendments and/or arguments and is withdrawn.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119 (e ) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, U.S. Provisional Application No. 62/805,271 (filing date 02/13/2019), 62/852,224 (filing date 05/23/2019), and 62/852,228 (filing date 05/23/2019) fail to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. The applications fail to provide support for the claims under examination, since there is no disclosure therein of “[A] method of editing a glucose-6-phophatase (G6PC) polynucleotide comprising a single nucleotide polymorphism (SNP) associated with Glycogen Storage Disease Type 1a (GSD1a), the method comprising contacting the G6PC polynucleotide with a base editor in a complex with one or more guide polynucleotides, wherein the base editor comprises a nucleic acid programmable DNA binding protein (napDNAbp) domain and an adenosine deaminase domain comprising an amino acid sequence having at least 85% sequence identity to SEQ ID NO: 3, wherein the adenosine deaminase domain comprises at least one alteration selected from the group consisting of I76Y, V82S, Y147T, Y147R, Q154S, and T166R referenced to SEQ ID NO: 3, and wherein one or more of said guide polynucleotides target said base editor to effect an A˖T to G˖C alteration of the SNP associated with GSD1a.” (Claim 1).
Therefore the filing date of claim 1 and dependent claims, are deemed to have priority date of July 19, 2019, which is the filing date of US Provisional Application No.62/876,354, because this application includes the first disclosure of elements of claim 1.
Response to Arguments
Applicant's arguments filed 10/14/2025 have been fully considered but they are not persuasive.
Applicant states “Applicant respectfully disagrees and asserts that the present application is, in fact, entitled to claim priority from US Provisional Patent Application No. 62/805,271, filed February 13, 2019, 62/852,224 filed May 23, 2019, and 62/852,228, filed May 23, 2019”. Applicant does not provide reasons for argument. Examiner searched for a “method of editing G6PC polynucleotide comprising a single nucleotide polymorphism (SNP) associated with Glycogen Storage Disease type 1a (GSD1a)” mentioned in the Provisional Applications without success. The first time the subject matter and method of gene editing this particular gene appeared, was in Provisional Application No. 62/876,354 filed July 19, 2019.
Drawings
The Replacement sheets for Drawings and Figures 3B, 19, 20 and 24 filed 10/14/2025 are hereby acknowledged and are acceptable.
Specification
Clean and amended copy of Specification filed 10/14/2025 is hereby acknowledged and is acceptable.
The following rejections are new and necessitated by Applicant’s amendments:
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 non-obviousness.
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, 23, 25-27 and 130 are rejected under 35 U.S.C. §103 as being unpatentable over Joung (Joung, J.K. et al. US Patent 11,946,040 B2, published April 2, 2024, benefiting from priority of US Application No. 16/781,979 filed February 4, 2020 and Provisional Application Nos. 62/844,717 filed May 7, 2019 and 62/800,974 filed February 4, 2019), Liu (Lui, D. et al. WO2018/027078 A1, published February 08, 2018; cited on IDS filed 06/10/2022; previously cited) and Skakic (Skakic, A. et al. “CRISPR/Cas9 genome editing of SLC37A4 gene elucidates the role of molecular markers of endoplasmic reticulum stress and apoptosis in renal involvement in glycogen storage disease type 1b”. Gene, Vol. 703 (2019), pp: 17-25 ; published online April 03, 2019; previously cited).
Regarding claims 1 and 130, A search for SEQ ID NO: 3 lead to the following result (Qy, Query = SEQ ID NO: 3; Db, Database = SEQ ID NO: 34 of US Patent No. 11,946,040 (Joung)):
RESULT 1
US-16-781-979-34
(NOTE: this sequence has 13 duplicates in the database searched.
See complete list at the end of this report)
Sequence 34, US/16781979
Patent No. 11946040
GENERAL INFORMATION
APPLICANT: THE GENERAL HOSPITAL CORPORATION
TITLE OF INVENTION: ADENINE DNA BASE EDITOR VARIANTS WITH REDUCED OFF-TARGET RNA
TITLE OF INVENTION: EDITING
FILE REFERENCE: 29539-0387001
CURRENT APPLICATION NUMBER: US/16/781,979
CURRENT FILING DATE: 2020-02-04
PRIOR APPLICATION NUMBER: 62/844,717
PRIOR FILING DATE: 2019-05-07
PRIOR APPLICATION NUMBER: 62/800,974
PRIOR FILING DATE: 2019-02-04
NUMBER OF SEQ ID NOS: 106
SEQ ID NO 34
LENGTH: 167
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Description of Artificial Sequence: Synthetic
polypeptide
Query Match 100.0%; Score 874; Length 167;
Best Local Similarity 100.0%;
Matches 167; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MSEVEFSHEYWMRHALTLAKRARDEREVPVGAVLVLNNRVIGEGWNRAIGLHDPTAHAEI 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MSEVEFSHEYWMRHALTLAKRARDEREVPVGAVLVLNNRVIGEGWNRAIGLHDPTAHAEI 60
Qy 61 MALRQGGLVMQNYRLIDATLYVTFEPCVMCAGAMIHSRIGRVVFGVRNAKTGAAGSLMDV 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 MALRQGGLVMQNYRLIDATLYVTFEPCVMCAGAMIHSRIGRVVFGVRNAKTGAAGSLMDV 120
Qy 121 LHYPGMNHRVEITEGILADECAALLCYFFRMPRQVFNAQKKAQSSTD 167
|||||||||||||||||||||||||||||||||||||||||||||||
Db 121 LHYPGMNHRVEITEGILADECAALLCYFFRMPRQVFNAQKKAQSSTD 167
US Patent No. 11,946,040, hereafter referred to as Joung, teaches a sequence 100% identical to SEQ ID NO: 3 of instant application, in the form of SEQ ID NO: 34. Joung also teaches “Adenine DNA Base Editor variants with reduced Off-target RNA editing” (see title and abstract). Joung teaches modifying/mutating the Adenine DNA Base editor at different positions to obtain variants with reduced off-target editing, presenting some of them and their activities in Figure 15A-D.
Regarding claims 1 and 130, Joung teaches variants V82G in Figures 15A-B,
and 16A-B. Joung teaches that modifying residues I76, V82, D147, Q154 and substituting these residues will generate ABE variants with reduced RNA editing and therefore less Off-targets events (see Table A, columns 10-11). Joung teaches that the mutations can include substitutions with any other amino acid other than the WT amino acid (see column 11, lines 65-66).
Joung also teaches that “In some embodiments, the base editors include programmable DNA binding domains such as engineered C2H2 zinc-fingers, transcription activator effector-like effectors (TALEs), and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) Cas RNA-guided nucleases (RGNs) and their variants, including ssDNA nickases (nCas9) or their analogs and catalytically inactive dead Cas9 (dCas9) and its analogs (e.g., as shown in Table C), and any engineered protospacer-adjacent motif (PAM) or high-fidelity variants (e.g., as shown in Table D). A programmable DNA binding domain is one that can be engineered to bind to a selected target sequence.” (see column 13, lines 6-18).
Regarding claim 130, Joung teaches using a ABE variant, wherein the CRISPR-Cas nuclease is a Cas9 or Cas12a that has ssDNA nickase activity or is a catalytically inactive Cas9 or Cas12a (see claim 8, column 193).
Joung also teaches that “ABEs have been used successfully for installation of A-to-G substitutions in multiple cell types and organism and could potentially reverse a large number of mutations known to be associated with human disease” (see column 1 at lines 65-67, and column 2, lines 1-4)
Joung does not teach a method of editing a G6PC polynucleotide comprising a SNP associated with GSD1a. However, Liu does teach G6PC and GSD1a.
Liu also teaches a method of gene editing using a fusion protein comprising a Cas9 (e.g., a Cas9 nickase) domain and adenosine deaminase domain that deaminate adenosine in DNA (see “[A]bstract” section). Liu teaches that the recombinant fusion protein Cas9 / ecTadA can create an A to G mutation (see ¶ [0005]-[0009]). Liu teaches that the fusion proteins provided improve the base editing activity (e.g. efficiency, selectivity, and specificity) (¶ [00237], line 4). Figure 15 shows the development of ABE while Figure 14 shows an example of A to G editing in mammalian cells.
Liu teaches that ABE adenosine deaminase can be obtained by directed evolution experiments for codon optimization (see ¶ [00400]) ; and Liu teaches experimentations of evolution from #1 to #7 in ¶ [00400] to [00428]. Liu teaches that evolution #2 gives rise to an amino acid residue change at position 147 from aspartic acid to Tyrosine (D>Y = Y147) (see Figure 128).
Liu does teach multiple mutations that can be accumulated in a TadA protein from E.coli and can be selected in vitro to enhance base editing efficiency (see “Base editor Efficiency”, page 392, ¶ [00357]).
Liu teaches a mutated TadA protein comprising one additional, or more mutations, including D147Y and Q154H (see pages 602-603, claims 49,50, 53 and Figure 23, e.g., pNMG-173 (pCMV_Cas9n_XTEN_ecTadA_GGS_NLS; H8Y_D108N_S127S_D147Y_Q154H).
Liu teaches that “In some embodiments, the adenosine deaminase comprises one or more of H8X, R26X, M61X, L6SX, M70X, A106X, D108X, A109X, N127X, D147X, R152X, Q154X, E155X, K161X, Q163X, and/or T166X mutation in SEQ ID NO: 1”, where X indicates any other amino acid than the corresponding amino acid in the wild type adenosine deaminase (see [00248]).
Liu also teaches that targeted editing of nucleic acid sequences is a highly promising approach to provide new therapies for human genetic diseases (see [0001]).
Liu teaches that one of diseases can be a glycogen storage disease, hypoglycemia with deficiency of glycogen synthetase in the liver (see page 171-172 [00353]). Liu specifically teaches that the targeted editing system can be used for Glycogen Storage Disease type 1A with mutations in G6PC and other mutation affecting Glucose-6-phosphate transport defect (see page 268, Table 2 “Target mutations that may be corrected using nucleobase editors, including exemplary gRNA sequences, gRNA sequences in the table correspond to SEQ ID NOs: 740-5526 from top to bottom”).
Liu teaches that the SNP that can be corrected using the claimed system is c.551G>A (p.Gly184Glu) in G6PC gene.
Furthermore, Skakic actually teaches a method of editing a glucose-6-phosphate translocase (G6PT or SLC37A4) polynucleotide comprising introducing a single nucleotide polymorphism (SNP) associated with Glycogen Storage Disease type 1b (GSD1b), the method comprising contacting the G6PT polynucleotide with a complex comprising a polynucleotide encoding a protein with a programmable DNA binding domain and one guide RNA, wherein the said guide RNA targets and effect an alteration to the wild type gene to obtain the SNP associated with GSD1b in a cell model (see title and “[A]bstract” section).
Skakic teaches the use of Cas9/gRNA and single strand oligonucleotide (ssODN) to obtain a human variant c.248G>A into the SLC37A4 locus and reproducing the mutation Gly83Glu responsible for GSD1b in two unrelated patients from Serbia (see section 2.1, page 18, and Figure 1 on page 19). Skakic therefore, in consequence of using a method of editing comprising a Cas9/gRNA system, establishes a novel in vitro model for GSD1b (see section 3.1, page 20).
Therefore, Skakic shows that targeting a polynucleotide encoding an enzyme involved in Glycogen Storage Disease 1 for gene editing is actually feasible using a Cas9/gRNA system, and effecting a single nucleic acid exchange is feasible using the method.
It would have been obvious to one with ordinary skills in the art before the effective filing date of the claimed invention to have adapted the gene editing method of Joung and Liu, using a recombinant fusion protein Cas9 with a modified TadA taught by Liu, and created or modified a SNP responsible for GSD1 in a G6PC enzyme as taught by Liu and Skakic . It would have been a substitution of one cas9/gRNA system taught by Skakic for another Cas9/gRNA system, wherein the Cas9 is a fusion protein taught by Joung and Liu, with the capability of operating with less off-target RNA editing, allowing for a higher accuracy for base editing due to the mutated adenine deaminase base editor domain of TadA comprising alterations, including Y147 and Q154. It would have been obvious to have tried and tested multiple types of amino acid substitutions as suggested by Joung at the position suggested by Joung, to obtain an effective recombinant protein with high efficiency. One with reasonable skills in the art motivated in higher accuracy, and motivated in treating or editing a G6PC enzyme, could have performed these substitutions with a reasonable expectation of success as shown by Skakic and would arrived at the claimed invention.
Regarding claim 23, Joung teaches that in one embodiment, the adenosine deaminase includes a wild type or engineered E. coli TadA monomer (see column 2, lines 34-35). Liu teaches that the adenosine deaminase domain is a monomer comprising an adenosine deaminase variant or a heterodimer comprising a wild-type adenosine deaminase domain and an adenosine deaminase variant (see ¶ [0003]-[0004] and figure 140).
Regarding claim 25, Joung teaches adenosine deaminase domain comprising amino acid alteration I76, V82, F149 and Q154 (see table A). As seen in the alignment above, Joung teaches these alterations in reference to SEQ ID NO: 3, in the form of SEQ ID NO: 34. Joung also teaches that the amino acid substitutions can be any other amino acid but the wild type amino acid (see column 11).
Regarding claim 26, Joung teaches H123 amino acid position, as a
position that would decrease off-target editing once substituted (see Table A). Liu teaches a substitution H123Y in multiple engineered ABEs. For example, in Table 4, page 410, pNMG-336 (L84F_A160V_D108N_H123Y_D147Y_E155V_I156Y). Liu also teaches that “In some embodiments, the adenosine deaminase comprises one or more of H8Y, R26W, M611, L6SQ, M70V, A106T, D108N, Al09T, N127S, D147Y, R152C, Q154H or Q154R, E155G or E155V or E155D, K161Q, Q163H, and/or T166P mutation (see [00248]).
Regarding claim 27, Liu teaches ABEs modified with multiple amino acids substitutions, for example in Table 4, pNMG-162(H8Y_D108N_S127S_D147Y_Q154H).
Liu also teaches “In some embodiments, the adenosine deaminase comprises
one, two, three, four, five, six, seven, or eight mutations selected from the group consisting of H8Y, M611, M70V, D128N, N127S, Q154R, E155G and Q163H (see [00250]).
Regarding claims 23, 25-27, the obviousness of combining the references Joung and Liu, and Skakic has been described above.
Claims 6 and 8-9 are rejected under 35 U.S.C. §103 as being unpatentable over Joung ( Joung, J.K. et al. US Patent 11,946,040 B2, published April 2, 2024, benefiting from priority of US Application No. 16/781,979 filed February 4, 2020 and Provisional Application Nos. 62/844,717 filed May 7, 2019 and 62/800,974 filed February 4, 2019), Liu (Lui, D. et al. WO2018/027078 A1, published February 08, 2018; cited on IDS filed 06/10/2022; previously cited), and Skakic (Skakic, A. et al. “CRISPR/Cas9 genome editing of SLC37A4 gene elucidates the role of molecular markers of endoplasmic reticulum stress and apoptosis in renal involvement in glycogen storage disease type 1b”. Gene, Vol. 703 (2019), pp: 17-25 ; published online April 03, 2019; previously cited), as applied to claim 1 above and in further view of Chou (Chou, J.Y. et al. “Mutations in the Glucose-6-Phosphatase-α (G6PC) gene that cause type Ia Glycogen Storage Disease”. Human Mutation, Vol. 29, No. 7 (2008), pp: 921-930; previously cited).
The rejection of claim 1 is described above. The elements of claim 1 are rendered obvious by the combination of references Joung, Liu and Skakic.
Liu teaches a gene editing system and gRNA to specifically correct the amino acid substitution p.Gly184Glu in G6PC responsible for Glycogen Storage Disease type 1A.
However, the elements of claims 6, 8-9 are not rendered obvious by the combination of these references, i.e, SNP associated with GSD1a at amino acid position 347 ( a non-glutamine) in G6PC polypeptide or amino acid position 83 (a non-arginine).
However, Chou teaches different types of GSD1, and that GSD1a and GSD1b have been characterized at the molecular level (see “[I]ntroduction”, left column, lines 1-12). Chou teaches a list of mutations described in prior art in Table 1, in which a non-glutamine amino acid substitution at position 347 and a non-arginine amino acid substitution at position 83 are taught (see page 924, Table 1)
Regarding claims 6, 8 and 9, Chou teaches a list of G6PC mutations associated with GSD1a (see Table 1). Chou teaches a G6PC having a non-glutamine (X) amino acid at position 347 or a non-arginine (X) amino acid at position 83 (see Table 1, Table 2 and figure 3). Chou teaches that p.Q347X is truncated by 11 amino acids at the carboxyl terminus, therefore is truncated, i.e. prematurely terminated (see page 926, left column, second ¶). Chou teaches in Table 2, that 33% of Caucasians with GSD1a carry a p.R83C mutation, 98% of Jewish with GSD1a carry a p.R83C mutation and 18% of Caucasians with GSD1a carry a p.Q347X mutation. Chou teaches that the prevalent mutations identified in the 676 alleles from Caucasian GSD1a patients are p.R83C (33%) and p.Q347X (18%) (see page 926, right column, lines 22-23).
Chou teaches an updated list of mutations in G6PC responsible for GSD1a and teaches about the genetic heterogeneity (see Table 1, pages 924-925).
Chou also teaches about the possibilities of genetic modifiers responsible for the phenotype, in view of the established phenotype heterogeneity and lack of a stringent genotype-phenotype association in GSD1a (See page 927, “[F]uture prospects” section, right column, lines 1-7). Chou states that even with current level of understanding of the mutations and their consequences, there are no current alternatives to the standard of care (same ¶, lines 7-10), thus the efforts towards gene therapy. Chou also teaches that gene therapy, with somatic replacement of G6PC activity does not produce equivalent recovery in the kidney and liver, and does not produce sustainable recovery (see page 927, right column, lines 9-25). The gene therapy so far does not provide sustainable recovery, while life-threatening events occur later in life of subjects with GSD1a (see same, lines 25-31), therefore there is a motivation for establishing stable genetic modifications and for specifically analyzing each mutation in search of genetic modifiers.
Liu and Skakic teach that a method of editing specific SNP can be applied to a SNP causing GSD1.
Therefore, it would have been obvious to one with ordinary skills in the art before the effective filing date of the claimed invention to have combined the teachings of Joung, Liu, Skakic and Chou and substituted the SNP taught by Liu with Q347X and R83C or R83H (Table 1), since these two SNPs are most prevalent as taught by Chou. A gene editing system taught by Joung and Liu, could have been used to modify the G6PC gene and alter a SNP associated with GSD1a. One with ordinary skills in the art, motivated in treating GSD1a and effecting a SNP responsible for GSD1a could have performed this modification and obtain a method of editing a G6PC polynucleotide.
The level of skills in the art is high. Skakic teaches that one with ordinary skills in the art can use a Cas9/gRNA gene editing system and apply it to a gene related to GSD1. Therefore, one motivated in editing and transforming a SNP responsible for GSD1 could have performed editing of a mutated genomic sequence to obtain a wild-type sequence.
Joung and Liu teach that specific genetic targeting and specific A to G alteration can be obtained using recombinant fusion protein with TadA and Cas9 modified by molecular evolution and codon optimization for specificity and efficiency, and avoiding off-target events.
One motivated in effecting an A to G alteration in a SNP associated with GSD1a for treating the disorder or studying other genetic modifiers in a model system, could have used the method taught by Joung/Liu, modified by Chou, on a G6PC polynucleotide comprising a prevalent SNP associated with GSD1a as taught by Chou, with a reasonable expectation of success, as taught by Skakic.
Therefore, the combination of Joung, Liu, Skakic and Chou renders the elements of claims 6, 8-9 obvious and unpatentable.
Response to Arguments
Applicant's arguments filed 10/14/2025 have been fully considered but they are not persuasive.
Applicant argues on page 16 of Remarks, that “It is well established that to support a prima facie obviousness rejection, the cited references must suggest all the elements in a claim.”
In response, Joung teaches the modification and engineering of ABEs to obtain mutants capable of editing RNA with less off-target events. In the list of amino acid residues to be substituted, all the claimed positions are taught by Joung. Joung also teaches that any other amino acid can be substituted in place of said residues. Liu teaches recited amino acid positions, recited substitutions and recited combination of mutations, and codon optimizations. Liu also teaches using the system comprising Cas9 or Cas12 nuclease domain in the recombinant protein for correcting a specific SNP responsible for GSD1a in G6PC. Skakic teaches that the method of gene editing is used successfully in the context of GSD1. Chou teaches that the recited SNPs are actually prevalent in GSD1a affecting Caucasian populations. Therefore, there is motivation to substitute one SNP for a prevalent one such as Q347X or R83X.
Therefore, in response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, all the elements recited in the claims are present and taught in prior art.
Conclusion
No Claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/A.D./Examiner, Art Unit 1636
/NANCY J LEITH/Primary Examiner, Art Unit 1636