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 .
Priority
The instant application, filed 12/14/2022 is a national stage entry under 35 USC 371 of PCT/CN2020/101936 (filed 07/14/2020). Also, acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in parent Application No. CN202010616648.7 , filed on 07/01/2020.
Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e). Failure to provide a certified translation may result in no benefit being accorded for the non-English application. Thus, the earliest possible priority for the instant Application is 07/14/2020.
Election/Restrictions
Applicant's election with traverse of Group I (claims 1-2, and 30-33), drawn to a method for activating γ-globin gene expression, comprising the following operations: a sequence of NTG-N(7-8)-WGATAR or NAG-N(7-8)- WGATAR is artificially produced in the sense strand or antisense strand of the promoter region of γ-globin gene by gene editing technology, forming an enhancer element comprising the NTG-N(7-8)-WGATAR sequence, NAG-N(7-8)-WGATAR sequence or reverse complementary sequence thereof in the promoter region of γ-globin gene, wherein the reverse complementary sequence of WGATAR is YTATCW, wherein W is T or A, R is A or G, Y is T or C, and N is A, G, C or T, in the reply filed on 03/27/2026 is acknowledged. Applicants further elect with traverse SEQ ID NO: 54 for the species s of the nucleotide sequence of the ssODN.
The traversal is on the ground(s) that Gori et al. (WO2017160890A1) does not teach the common technical feature of an NTG-N(7-8)-WGATAR sequence, NAG-N(7-8)-WGATAR sequence artificially produced to form an enhancer element comprising the NTG-N(7-8) WGATAR sequence, NAG-N(7-8)-WGATAR sequence, or reverse complementary sequence thereof, in the promoter region of γ-globin gene. Applicants specifically argue that Gori et al. refers to the known GATA1 binding motif (CTATCT, ATATCT) and a specific nucleic acid contains NTG at 7-8 bases upstream of GATA motif, but fails to teach a sequence of NTG-N(7-8) WGATAR or NAG-N(7-8)-WGATAR, which is different from the instant GATA motif (CTATCT meets he claim limitation YTATCW, but ATATCT not), could be used as a new motif for activating γ-globin gene expression. Also, applicants argue that the template nucleic acid comprising SEQ ID NO: 906 is only one of numerous gRNAs disclosed in Gori et al., it is unobvious to a person skilled in the art to generalize a motif of a sequence of NTG-N(7-8) WGATAR or NAG-N(7-8)-WGATAR capable of activating γ-globin gene expression.
This is not found persuasive because although Gori et al. discloses only CTATCT, instant claim 1 requires that the sequence artificially produced in the promoter region of γ-globin gene is NTG-N(7-8)-WGATAR or NAG-N(7-8)- WGATAR or reverse complementary sequence thereof, but not both sequence.
The CTATCT sequence of Gori et al. reads on the instant claimed YTATCW sequence, which is the reverse complementary sequence of the claimed WGATAR sequence. Also, regarding applicants’ argument that the template nucleic acid comprising SEQ ID NO: 906 is only one of numerous gRNAs disclosed in Gori et al. and it would be unobvious to a PHOSITA to generalize a motif of the claimed sequences capable of activating γ-globin gene expression, this is unpersuasive because although SEQ ID NO: 906 is one example of many gRNAs disclosed in Gori et al., MPEP 2123 (I) states “A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Labs., Inc. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989). Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971),”
The requirement is still deemed proper and is therefore made FINAL.
Claims 1-2, 6-7, 10, 14, 20-21, 23, 27, and 30-39 are pending in the instant application.
Claims 6-7, 10, 14, 20-21, 23, 27, and 34-39 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. Applicant timely traversed the restriction (election) requirement in the reply filed on 03/27/2026. Therefore, claims 1-2 and 30-33 are under examination in the instant application.
Claim Objections
Claim 1 is objected to because of the following informalities:
Claim 1 recites, “the NTG-N(7-8)-WGATAR sequence, NAG-N(7-8)-WGATAR sequence or reverse complementary sequence thereof”. To avoid insufficient antecedent basis issues, an “or” should be added in line 5 and an “a” in line 6 to read as the NTG-N(7-8)-WGATAR sequence, or NAG-N(7-8)-WGATAR sequence, or a reverse complementary sequence thereof.
Appropriate correction is required.
Claim Rejections - 35 USC § 102
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) 1-2 and 30-33 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Gori et al. (WO2017160890A1, filed on 03/14/2017).
Regarding claim 1, Gori et al. teaches a method for increasing expression (i.e., transcriptional activity) of one or more γ-globin genes (e.g., HBG1, HBG2, or HBG1 and HBG2) in a subject or cell using a genome editing system (e.g., CRISPR/Cas-mediated genome editing system) (SUMMARY OF THE INVENTION, page 5, claims 1-4, 8, and 194). Gori et al. also teaches that the method utilizes a DNA repair mechanism, e.g., HDR to alter, including mutate, insert, delete or disrupt, the sequence of one or more nucleotides in γ-globin gene regulatory element (e.g., promoter). (SUMMARY OF THE INVENTION, page 5). Gori et al. also discloses a gRNA for use in the method, which gRNA comprises: a targeting domain complementary to a target domain in a γ-globin gene regulatory region, wherein the regulatory region to a DNA sequence comprising one or more regulatory elements (e.g., silencer, enhancer, promoter, or insulator) controlling or regulating expression of a gene (page 13, paragraph 1 and page 34, paragraph 4). Gori et al. teaches that the HBG1 regulatory region is located in the region spanning nucleotides 1-2990 of SEQ ID NO:902 and the HBG2 regulatory region is located in the region spanning nucleotides 1-2914 of SEQ ID NO:903 (claims 3-4). HBG1 and HBG2 promoter elements that are altered to recreate HPFH mutations include GATAl binding motifs, such as CTATCT (page 18, paragraph 4). CTATCT reads on the claimed YTATCW sequence, which is the reverse complementary sequence of the claimed WGATAR sequence produced in the sense strand or antisense strand of the gene promoter. Gori et al. also teaches a nucleic acid composition comprising a nucleotide sequence that encodes the gRNA that comprises a template nucleic acid that is a is a single stranded oligodeoxynucleotide (ssODN) of SEQ ID NO: 906 that, contains NTG and 5' and 3' homology arms (range up to about 200 nucleotides in length) at 7-8 bases upstream of GATA motif (claims 34, 102-103, and 116).
Regarding claim 2: Following discussion of claim 1 above, Gori et al. further teaches that the method may utilize any repair mechanism to alter (e.g., delete, disrupt, or modify) all or a portion of one or more γ-globin gene regulatory elements, such as a DNA repair mechanism, e.g., NHEJ or HDR to delete or disrupt one or more γ-globin gene regulatory elements (e.g., silencer, enhancer, promoter, or insulator) (SUMMARY OF THE INVENTION, page 5). This reads on that the NTG-N(7-8)-WGATAR sequence, NAG-N(7-8)-WGATAR sequence or reverse complementary sequence thereof is produced by one or more means selected from a group consisting of deletion, insertion, mutation, and any combination thereof.
Regarding claim 30: Following discussion of claim 1 above, Gori et al. teaches HBG1 and HBG2 promoter elements that are altered to recreate HPFH mutations include GATAl binding motifs, such as CTATCT (page 18, paragraph 4). CTATCT is the reverse complementary sequence of the claimed WGATAR sequence produced in the sense strand or antisense strand of the gene promoter at 7-8 bases upstream of GATA motif.
Regarding claim 31, it is noted that the claimed positions -428 to -66 of the HBG1 gene promoter region corresponds to positions 957-1319 of instant SEQ ID NO: 1 of the HBG1 gene.
Following discussion of claim 30 above, Gori et al. teaches that the HBG1 regulatory region is located in the region spanning nucleotides 1-2990 of SEQ ID NO:902 (claim 3). Gori et al. specifically discloses positions 2510-2872 of SEQ ID NO: 902 of the HBG1 gene, which is identical to positions 957-1319 of instant SEQ ID NO: 1 of the HBG1 gene (i.e. positions -428 to -66 of the HBG1 gene promoter region as claimed) (please see below a screenshot of the query match).
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Regarding claim 32, it is noted that the claimed positions -92 to -66 of the HBG1 gene promoter region corresponds to positions 1293-1319 of instant SEQ ID NO: 1 of the HBG1 gene.
Following discussion of claim 30 above, Gori et al. teaches that the HBG1 regulatory region is located in the region spanning nucleotides 1-2990 of SEQ ID NO:902 (claim 3). Gori et al. specifically discloses positions 2846-2872 of SEQ ID NO: 902 of the HBG1 gene, which is identical to positions 1293-1319 of instant SEQ ID NO: 1 of the HBG1 gene (i.e. positions -92 to -66 of the HBG1 gene promoter region as claimed) (please see below a screenshot of the query match).
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Regarding claim 33, it is noted that the claimed positions -129 to -98 of the HBG1 gene promoter region corresponds to positions 1256-1287 of instant SEQ ID NO: 1 of the HBG1 gene.
Following discussion of claim 1 above, Gori et al. teaches that the HBG1 regulatory region is located in the region spanning nucleotides 1-2990 of SEQ ID NO:902 (claim 3). Gori et al. specifically discloses positions 2809-2840 of SEQ ID NO: 902 of the HBG1 gene, which is identical to positions 1256-1287 of instant SEQ ID NO: 1 of the HBG1 gene (i.e. positions -129 to -98 of the HBG1 gene promoter region as claimed) (please see below a screenshot of the query match).
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Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HANAN ISAM ABUZEINEH whose telephone number is (571)272-9596. The examiner can normally be reached Mon- Fri 8:30-5:00.
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Hanan Isam Abuzeineh
/H.I.A./ Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/ Supervisory Patent Examiner, Art Unit 1633
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