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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 05/20/2026 has been entered.
This action is in response to the amendment filed 05/20/2026, in which claims 1, 13-15 and 23 were amended and claims 25-28 were newly added. Claims 1, 10-15, 18-20 and 22-28 are currently pending and under examination.
Applicant' s arguments have been thoroughly reviewed, but are not persuasive for the
reasons that follow. Any rejection and objections not reiterated in this action have been
withdrawn.
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.
Claims 12 and 13 are 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 12 depends on claim 1 and recites “wherein the at least one base-editing enzyme is a cytidine deaminase”, however claim 1 only recites cytidine deaminases and specific cytidine deaminases at that, therefore, claim 12 does not further limit claim 1. Claim 13 depends on claim 12 which depends on claim 1 and recites “wherein the cytidine deaminase comprises an amino acid sequence as set forth in SEQ ID NOs: 5-12”, however, the sequences listed as SEQ ID NOs: 5-12 are not the sequences of the specific cytidine deaminases listed in claim 1. Therefore, claim 13 does not include all of the limitations of claim 1 as well as does not further limit claim 1. Applicant 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.
Response to Amendment - Claim Rejections - 35 USC § 112
The previous rejection of claims 6 and 8 under 35 U.S.C. 112(b) has been withdrawn in view of Applicant’s cancellation of the claims filed on 05/20/2026.
The previous rejection of claims 15 and 23 under 35 U.S.C. 112(b) has been withdrawn in view of Applicant’s amendments of the claims filed on 05/20/2026.
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1, 10-15, 18-20 and 22-28 are rejected under 35 U.S.C. 103 as being unpatentable over Bryson et al (WO 2019/217942 A1; Cited in a prior Office Action) in view of Walton et al (Science 368, 1-7; April 17th, 2020) and Weber et al (Sci. Adv. Feb. 12th, 2020; 6: eaay9392; Pgs. 1-14). This is a new rejection, necessitated by the amendment filed 05/20/2026.
Regarding claims 1, 12 and 14, the claim is interpreted that “a sequence” (specifically, “a nucleotide sequence” and “a target sequence”) means two or more consecutive amino acids/nucleotides and not the entirety of the sequence.
Bryson teaches increased levels of fetal hemoglobin (HbF) can ameliorate the clinical course of inherited disorders of beta-globin gene expression, such as beta thalassemia and sickle cell anemia, and in a group of disorders called hereditary persistence of fetal hemoglobin (HPFH), the expression of one or both of the gamma globin genes (HBG1/2) of HbF persists at high levels in adult erythroid cells. [0562]. Bryson teaches a method of editing an HBG1 or HBG2 gene loci using a targeted base editor and a guide RNA in CD34+ cells to increase expression of the gamma globin [0564-0565 and 0567]. Bryson teaches guide RNAs, specifically gRNA1, used within the system with 100% identity to two or more consecutive nucleotides of instant SEQ ID NOs: 52 and 53 (See NEW Appendices I and II; [0565] denoted as gRNA1). Bryson teaches the guide RNA is capable of targeting a sequence within the HBG1/2 promoter in the -200 region that has 100% identity to two or more consecutive nucleotides of instant SEQ ID NOs: 19 and 20 (See NEW Appendices III and IV; Page 200, Table 4, Line 63). Bryson teaches that the multiplex editing can comprise one or more base editor system with a plurality of guide polynucleotides [0452]. Bryson teaches multiple Cas9n variants to be fused to a APOBEC cytidine deaminase (Page 128, Table 1 and [0417]), thus the combination of the spCas9n variant targeting NGN PAM fused with the APOBEC1 domain would produce the CBE-SpG base editing enzyme.
Bryson does not teach the specific use of the CBE-SpG base editing enzyme.
Walton teaches the generation of a highly enzymatically active NGN PAM variant (named SpG), and subsequent optimization of SpG led to a variant (named SpRY) capable of editing nearly all PAMs and that SpG and SpRY improve editing resolution and offer previously unrealized genome editing capabilities (Page 1, Second Column). Walton teaches with SpG-CBEs, they were able to screen additional target sites for each substitution and efficiently introduce the intended C-to-T edit across all eight targets whereas with WT-CBE, they were unable to efficiently generate the intended edit for seven of eight substitutions, owing to the absence of nearby canonical PAMs (Page 7, Column 1).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Bryson to include the CBE-SpG base editor enzyme as taught by Walton because Bryson teaches it is within the ordinary skill in the art to use a method of editing an HBG1 or HBG2 gene loci using a targeted base editor (APOBEC1) and a guide RNA in CD34+ cells to increase expression of the gamma globin and Walton teaches the generation of a highly enzymatically active NGN PAM variant (named SpG), and subsequent optimization of SpG led to a variant (named SpRY) capable of editing nearly all PAMs and that SpG and SpRY improve editing resolution and offer previously unrealized genome editing capabilities.
One would have been motivated to make such a modification in order to receive the expected benefit of increased editing efficiency using CBE-SpG in HBG promoter editing as taught by Bryson and Walton.
Bryson and Walton do not teach the specific gene editing of -194 C>T, in a region in the HBG1 or HBG2 promoter, wherein a binding site for LRF is disrupted.
Weber teaches gRNAs for targeting within the -200 LRF binding site to disrupt the binding of LRF to induce HbF expression in adult HUDEP-2 erythroid cells (Page 3, Column 1). Weber teaches introducing point mutations specifically at -197, -196, and-195, within the -200 region and the-158 region at positions -158, -152, and -151 (Page 2, Fig 1A and Page 3, Column 1). Weber teaches the LRF region comprises from -203 to -194 (Page 2, Fig 1A).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have designed a guide RNA to target within the -200 region of the HBG2 promoter as taught by Weber. It would have amounted to applying the knowledge that targeting any of the nucleotides within the -200 region (-203, -202, -201, -200, -199, -198, -197, -196, -195 and/or -194) to induce a point mutation in order to disrupt the LRF binding and induce HbF expression in adult HUDEP-2 erythroid cells by known means to yield predictable results. The skilled artisan would have had a reasonable expectation of success in designing a guide RNAs for targeting within the -200 region of the HBG2 promoter to induce a point mutation because of the evidence in Weber, it was well-within the purview of the skilled artisan and routine in the art, to design a guide RNA for specifically targeting -194 for a C>T point mutation. Furthermore, Bryson teaches a method of editing an HBG1 or HBG2 gene loci using a targeted base editor (APOBEC1) and a guide RNA in CD34+ cells to increase expression of the gamma globin.
In combination, the skilled artisan would have been motivated to design a guide RNA for specifically targeting -194 for a C>T point mutation which would disrupt the binding of LRF to the HBG2 promoter because Bryson teaches editing an HBG1 or HBG2 gene loci using a targeted base editor (APOBEC1) and a guide RNA in CD34+ cells to increase expression of the gamma globin, specifically within the -200 region (Page 200, Table 4, Line 63), and coupled with Weber’s teachings that the targeting of the nucleotides within the -200 region using guide RNAs and that the LRF region comprises from -203 to -194, the skilled artisan would have been motivated to design a guide RNA for specifically targeting -194 for a C>T point mutation which would disrupt the binding of LRF to the HBG2 promoter as taught by Bryson and Weber.
Regarding claims 10 and 11, Bryson teaches wildtype SpCas9 sequence [0174]. Bryson teaches the mutation of H840A (within the HNH domain) completely inactivates the nuclease activity of S. pyogenes Cas9 resulting in a nickase [0182 and 0224-0225]. Therefore, with the sequence provided by Bryson [0174] for the SpCas9 with a single H840A mutation shows 100% identity to instant SEQ ID NO: 33 (See old Appendix VII; Cited in a prior Office Action).
Regarding claim 13, the claim is interpreted that “an amino acid sequence” means two or more consecutive amino acids and not the entirety of the sequence.
Bryson teaches the suitable nucleic-acid editing domains, e.g., deaminases and deaminase domains, that can be fused to Cas9 domains, such as the APOBEC3-G Human sequence which is 100% identical to instant SEQ ID NO: 5 (See NEW Appendix V; [0329] and Page 144).
Regarding claim 15, the claim is interpreted that “a sequence” (specifically, “a nucleotide sequence” and “a target sequence”) means two or more consecutive amino acids/nucleotides and not the entirety of the sequence.
Bryson teaches increased levels of fetal hemoglobin (HbF) can ameliorate the clinical course of inherited disorders of beta-globin gene expression, such as beta thalassemia and sickle cell anemia, and in a group of disorders called hereditary persistence of fetal hemoglobin (HPFH), the expression of one or both of the gamma globin genes (HBG1/2) of HbF persists at high levels in adult erythroid cells. [0562]. Bryson teaches a method of editing an HBG1 or HBG2 gene loci using a targeted base editor and a guide RNA in CD34+ cells to increase expression of the gamma globin [0564-0565 and 0567]. Bryson teaches instant SEQ ID NO: 50 as guide RNAs used within the system with 100% identity (See NEW Appendix VI) ([0565] denoted as gRNA1). Bryson teaches that the multiplex editing can comprise one or more base editor system with a plurality of guide polynucleotides [0452].
Bryson does not teach the specific use of the CBE-SpG base editing enzyme.
Walton teaches the generation of a highly enzymatically active NGN PAM variant (named SpG), and subsequent optimization of SpG led to a variant (named SpRY) capable of editing nearly all PAMs and that SpG and SpRY improve editing resolution and offer previously unrealized genome editing capabilities (Page 1, Second Column). Walton teaches with SpG-CBEs, they were able to screen additional target sites for each substitution and efficiently introduce the intended C-to-T edit across all eight targets whereas with WT-CBE, they were unable to efficiently generate the intended edit for seven of eight substitutions, owing to the absence of nearby canonical PAMs (Page 7, Column 1).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Bryson to include the CBE-SpG base editor enzyme as taught by Walton because Bryson teaches it is within the ordinary skill in the art to use a method of editing an HBG1 or HBG2 gene loci using a targeted base editor (APOBEC1) and a guide RNA in CD34+ cells to increase expression of the gamma globin and Walton teaches the generation of a highly enzymatically active NGN PAM variant (named SpG), and subsequent optimization of SpG led to a variant (named SpRY) capable of editing nearly all PAMs and that SpG and SpRY improve editing resolution and offer previously unrealized genome editing capabilities.
One would have been motivated to make such a modification in order to receive the expected benefit of increased editing efficiency using CBE-SpG in HBG promoter editing as taught by Bryson and Walton.
Regarding claims 18, 19 and 22, Bryson teaches increased levels of fetal hemoglobin (HbF) can ameliorate the clinical course of inherited disorders of beta-globin gene expression, such as beta thalassemia and sickle cell anemia, and in a group of disorders called hereditary persistence of fetal hemoglobin (HPFH), the expression of one or both of the gamma globin genes (HBGJ/2) of HbF persists at high levels in adult erythroid cells. [0562]. Bryson teaches a method of editing an HBG1 or HBG2 gene loci using a targeted base editor and a guide RNA in CD34+ cells to increase expression of the gamma globin [0564-0565 and 0567]. Bryson teaches a method of editing an HBB polynucleotide comprising a single nucleotide polymorphism (SNP) associated with sickle cell disease, the method comprising contacting the HBB polynucleotide with a base editor in complex with one or more guide polynucleotides, wherein the base editor comprises a polynucleotide programmable DNA binding domain and an adenosine deaminase domain, and wherein the one or more guide polynucleotides target the base editor to effect an A•T to G•C alteration of the SNP associated with sickle cell disease (Page 290, Claim 1).
Regarding claim 20, Bryson teaches a method of editing an HBG1 or HBG2 gene loci using a targeted base editor and a guide RNA in CD34+ cells to increase expression of the gamma globin [0564-0565 and 0567].
Regarding claim 23, the claim is interpreted that “a sequence” (specifically, “a nucleotide sequence” and “a target sequence”) means two or more consecutive amino acids/nucleotides and not the entirety of the sequence.
Bryson teaches increased levels of fetal hemoglobin (HbF) can ameliorate the clinical course of inherited disorders of beta-globin gene expression, such as beta thalassemia and sickle cell anemia, and in a group of disorders called hereditary persistence of fetal hemoglobin (HPFH), the expression of one or both of the gamma globin genes (HBG1/2) of HbF persists at high levels in adult erythroid cells. [0562]. Bryson teaches a method of editing an HBG1 or HBG2 gene loci using a targeted base editor and a guide RNA in CD34+ cells to increase expression of the gamma globin [0564-0565 and 0567]. Bryson teaches guide RNAs, specifically gRNA1, used within the system with 100% identity to two or more consecutive nucleotides of instant SEQ ID NOs: 52 and 53 (See NEW Appendices I and II; [0565] denoted as gRNA1). Bryson teaches the guide RNA is capable of targeting a sequence within the HBG1/2 promoter in the -200 region that has 100% identity to two or more consecutive nucleotides of instant SEQ ID NOs: 19 and 20 (See NEW Appendices III and IV; Page 200, Table 4, Line 63). Bryson teaches that the multiplex editing can comprise one or more base editor system with a plurality of guide polynucleotides [0452]. Bryson teaches multiple Cas9n variants to be fused to a APOBEC cytidine deaminase (Page 128, Table 1 and [0417]), thus the combination of the spCas9n variant targeting NGN PAM fused with the APOBEC1 domain would produce the CBE-SpG base editing enzyme.
Bryson does not teach the specific use of the CBE-SpG base editing enzyme.
Walton teaches the generation of a highly enzymatically active NGN PAM variant (named SpG), and subsequent optimization of SpG led to a variant (named SpRY) capable of editing nearly all PAMs and that SpG and SpRY improve editing resolution and offer previously unrealized genome editing capabilities (Page 1, Second Column). Walton teaches with SpG-CBEs, they were able to screen additional target sites for each substitution and efficiently introduce the intended C-to-T edit across all eight targets whereas with WT-CBE, they were unable to efficiently generate the intended edit for seven of eight substitutions, owing to the absence of nearby canonical PAMs (Page 7, Column 1).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Bryson to include the CBE-SpG base editor enzyme as taught by Walton because Bryson teaches it is within the ordinary skill in the art to use a method of editing an HBG1 or HBG2 gene loci using a targeted base editor (APOBEC1) and a guide RNA in CD34+ cells to increase expression of the gamma globin and Walton teaches the generation of a highly enzymatically active NGN PAM variant (named SpG), and subsequent optimization of SpG led to a variant (named SpRY) capable of editing nearly all PAMs and that SpG and SpRY improve editing resolution and offer previously unrealized genome editing capabilities.
One would have been motivated to make such a modification in order to receive the expected benefit of increased editing efficiency using CBE-SpG in HBG promoter editing as taught by Bryson and Walton.
Bryson and Walton do not teach the specific gene editing of -194 C>T, in a region in the HBG1 or HBG2 promoter, wherein a binding site for LRF is disrupted.
Weber teaches gRNAs for targeting within the -200 LRF binding site to disrupt the binding of LRF to induce HbF expression in adult HUDEP-2 erythroid cells (Page 3, Column 1). Weber teaches introducing point mutations specifically at -197, -196, and-195, within the -200 region and the-158 region at positions -158, -152, and -151 (Page 2, Fig 1A and Page 3, Column 1). Weber teaches the LRF region comprises from -203 to -194 (Page 2, Fig 1A).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have designed a guide RNA to target within the -200 region of the HBG2 promoter as taught by Weber. It would have amounted to applying the knowledge that targeting any of the nucleotides within the -200 region (-203, -202, -201, -200, -199, -198, -197, -196, -195 and/or -194) to induce a point mutation in order to disrupt the LRF binding and induce HbF expression in adult HUDEP-2 erythroid cells by known means to yield predictable results. The skilled artisan would have had a reasonable expectation of success in designing a guide RNAs for targeting within the -200 region of the HBG2 promoter to induce a point mutation because of the evidence in Weber, it was well-within the purview of the skilled artisan and routine in the art, to design a guide RNA for specifically targeting -194 for a C>T point mutation. Furthermore, Bryson teaches a method of editing an HBG1 or HBG2 gene loci using a targeted base editor (APOBEC1) and a guide RNA in CD34+ cells to increase expression of the gamma globin.
In combination, the skilled artisan would have been motivated to design a guide RNA for specifically targeting -194 for a C>T point mutation which would disrupt the binding of LRF to the HBG2 promoter because Bryson teaches editing an HBG1 or HBG2 gene loci using a targeted base editor (APOBEC1) and a guide RNA in CD34+ cells to increase expression of the gamma globin, specifically within the -200 region (Page 200, Table 4, Line 63), and coupled with Weber’s teachings that the targeting of the nucleotides within the -200 region using guide RNAs and that the LRF region comprises from -203 to -194, the skilled artisan would have been motivated to design a guide RNA for specifically targeting -194 for a C>T point mutation which would disrupt the binding of LRF to the HBG2 promoter as taught by Bryson and Weber.
Regarding claim 24, Bryson teaches increased levels of fetal hemoglobin (HbF) can ameliorate the clinical course of inherited disorders of beta-globin gene expression, such as beta thalassemia and sickle cell anemia, and in a group of disorders called hereditary persistence of fetal hemoglobin (HPFH), the expression of one or both of the gamma globin genes (HBGJ/2) of HbF persists at high levels in adult erythroid cells. [0562]. Bryson teaches a method of editing an HBG1 or HBG2 gene loci using a targeted base editor and a guide RNA in CD34+ cells to increase expression of the gamma globin [0564-0565 and 0567]. Bryson teaches a method of editing an HBB polynucleotide comprising a single nucleotide polymorphism (SNP) associated with sickle cell disease, the method comprising contacting the HBB polynucleotide with a base editor in complex with one or more guide polynucleotides, wherein the base editor comprises a polynucleotide programmable DNA binding domain and an adenosine deaminase domain, and wherein the one or more guide polynucleotides target the base editor to effect an A•T to G•C alteration of the SNP associated with sickle cell disease (Page 290, Claim 1).
Regarding claims 25-28, Bryson teaches increased levels of fetal hemoglobin (HbF) can ameliorate the clinical course of inherited disorders of beta-globin gene expression, such as beta thalassemia and sickle cell anemia, and in a group of disorders called hereditary persistence of fetal hemoglobin (HPFH), the expression of one or both of the gamma globin genes (HBG1/2) of HbF persists at high levels in adult erythroid cells. [0562]. Bryson teaches a method of editing an HBG1 or HBG2 gene loci using a targeted base editor and a guide RNA in CD34+ cells to increase expression of the gamma globin [0564-0565 and 0567]. Bryson teaches guide RNAs, specifically gRNA1, used within the system with 100% identity to two or more consecutive nucleotides of instant SEQ ID NOs: 52 and 53 (See NEW Appendices I and II; [0565] denoted as gRNA1). Bryson teaches the guide RNA is capable of targeting a sequence within the HBG1/2 promoter in the -200 region, specifically introducing point mutations as C. -202 C>T, -
201 C>T, -198 T>C, -197 C>T, -196 C>T, -195 C>G, that has 100% identity to two or more consecutive nucleotides of instant SEQ ID NOs: 19 and 20 (See NEW Appendices III and IV; Page 200, Table 4, Lines 62 and 63). Bryson teaches that the multiplex editing can comprise one or more base editor system with a plurality of guide polynucleotides [0452]. Bryson teaches multiple Cas9n variants to be fused to a APOBEC cytidine deaminase (Page 128, Table 1 and [0417]), thus the combination of the spCas9n variant targeting NGN PAM fused with the APOBEC1 domain would produce the CBE-SpG base editing enzyme.
Bryson does not teach the specific gene editing of -194 C>T, in a region in the HBG1 or HBG2 promoter, wherein a binding site for LRF is disrupted.
Weber teaches gRNAs for targeting within the -200 LRF binding site to disrupt the binding of LRF to induce HbF expression in adult HUDEP-2 erythroid cells (Page 3, Column 1). Weber teaches introducing point mutations specifically at -202 C>T, -201 C>T, -197 C>T, -196 C>T, and-195 C>T, within the -200 region and the -158 region at positions -158 C>T, -152, and -151 (Page 2, Fig 1A and Page 3, Column 1). Weber teaches the LRF region comprises from -203 to -194 (Page 2, Fig 1A).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have designed a guide RNA to target within the -200 region of the HBG2 promoter as taught by Weber. It would have amounted to applying the knowledge that targeting any of the nucleotides within the -200 region (-203, -202, -201, -200, -199, -198, -197, -196, -195 and/or -194) to induce a point mutation in order to disrupt the LRF binding and induce HbF expression in adult HUDEP-2 erythroid cells by known means to yield predictable results. The skilled artisan would have had a reasonable expectation of success in designing a guide RNAs for targeting within the -200 region of the HBG2 promoter to induce a point mutation because of the evidence in Weber, it was well-within the purview of the skilled artisan and routine in the art, to design a guide RNA for specifically targeting -194 for a C>T point mutation. Furthermore, Bryson teaches a method of editing an HBG1 or HBG2 gene loci using a targeted base editor (APOBEC1) and a guide RNA in CD34+ cells to increase expression of the gamma globin.
In combination, the skilled artisan would have been motivated to design a guide RNA for specifically targeting -194 for a C>T point mutation which would disrupt the binding of LRF to the HBG2 promoter as well as a plurality of guide RNAs to target multiple point mutations within the LRF and BCL11A binding sites because Bryson teaches editing an HBG1 or HBG2 gene loci using a targeted base editor (APOBEC1) and a plurality guide RNAs in CD34+ cells to increase expression of the gamma globin, specifically within the -200 region (Page 200, Table 4, Line 62 and 63), and coupled with Weber’s teachings that the targeting of the nucleotides within the -200 region using multiple guide RNAs and that the LRF region comprises from -203 to -194, the skilled artisan would have been motivated to design a guide RNA for specifically targeting -194 for a C>T point mutation which would disrupt the binding of LRF to the HBG2 promoter as taught by Bryson and Weber.
Response to Arguments - Claim Rejections - 35 USC § 103
The previous rejection of claims 1, 10-15, 18-20 and 22 under 35 U.S.C. 103 as being unpatentable over Bryson et al (WO 2019/217942 A1) in view of Wienert et al (Trends in Genetics, December 2018, Vol. 34, No. 12) has been withdrawn in view of Applicant’s amendments to the claims filed on 05/20/2026.
The previous rejection of claims 6 and 8 under 35 U.S.C. 103 as being unpatentable over Bryson et al (WO 2019/217942 A1) in view of Koblan et al (Nat Biotechnol 36, 843–846; 2018) and further in view of Wienert et al (Trends in Genetics, December 2018, Vol. 34, No. 12) has been withdrawn in view of Applicant’s cancellation of the claim filed on 05/20/2026.
The previous rejection of claims 23 and 24 under 35 U.S.C. 103 as being unpatentable over Bryson et al (WO 2019/217942 A1) in view of Koblan et al (Nat Biotechnol 36, 843–846; 2018) and further in view of Wienert et al (Trends in Genetics, December 2018, Vol. 34, No. 12) has been withdrawn in view of Applicant’s amendments to the claims filed on 05/20/2026.
Conclusion
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/ALEXANDRA ROSE LIPPOLIS/Examiner, Art Unit 1637
/CELINE X QIAN/Primary Examiner, Art Unit 1637
