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 .
The ejections under section 112(a) is withdrawn in view of Applicant’s amendments and remarks in connection with this ground of rejection. Namely, the claims have been amended to require CYBB cDNA encoding a functional gp91phox polypeptide.
The rejection under section 103 is withdrawn in favor of the following new ground of rejection, adding Sweeney et al., Human Gene Therapy. 2017;28(7):565-575, which was necessitated by Applicant’s amendments:
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1, 3-5, 7, 11, 12, 17, 21, 25, 27, 29-31, 41, 43, 44, 53, 54, 57, 58, 64, 65 are rejected under 35 U.S.C. 103 as being unpatentable over De Ravin et al., Science Translational Medicine, 11 January 2017 (2017-01-11) (De Ravin) in view of:
WO 2011/135002 (WO 002); or
EP 2019134 (EP 134); or
WO 2016/164356 (WO 356); or
WO 2020/074729 (WO 729); all in further view of:
Sweeney et al., Human Gene Therapy. 2017;28(7):565-575 (Sweeney).
De Ravin teaches a CRISPR CAS 9 method based on homologous recombination by editing the CYBB gene:
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De Ravin may fail to explicitly teach the required donor template which is CYBB cDNA which comprises a nucleotide having at least 80% identity to the one of SEQ ID NO:11. SEQ ID NO:11 is codon optimized exon 2-exon 13 while in De Ravin the donor substrate it is a small short ODN tag which corrects a point mutation in exon 7. There is knocking in of the gene in this method but only repair of the deleted part after homologous recombination of a short ODN for the exon 7-point mutation.
However, using a donor template comprising a cytochrome b-245 beta chain (CYBB) cDNA comprising a nucleotide sequence having at least 80% identity to SEQ ID NO:11 for CRISPR CAS 9 was within the purview of those ordinary skill. It is for that proposition that the rejection joins the secondary references:
WO 002 discloses the nucleic acid molecule of SEQ ID NO:11 encoding for the gp91phox or its expression in he human cells such as a hematopoietic cell.
In particular, the gp91phox encoded by the nucleic acid sequence of 3200-4912 of SEQ ID NO:1 (see [0013], [0018], [0025], [0047], Table 1).
The gene trap vector is used in gene therapy for the correction of chronic granulomatous disease, where it has preferably the structure depicted in Fig. 3 or 7 and has the sequence shown in SEQ ID NOs:1 to 5.
WO 002 demonstrates that gp91 in GT-SAgp91 transduced X-CGD cells is expressed from the endogenous promoter/enhancer elements of trapped genes.
According to Figure 1, the gene is integrated between E1 and E2:
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The query sequence SEQ ID NO:11 has 99.9 % identity (99.9 % similarity) over 1659 positions in a common overlap (range (q:s): 1-1659:3313-4971) with subject EM_PAT:JA639783 (length: 6837) of WO 002.
EP 134 also teaches a polynucleotide nucleic SEQ ID NO:11 encoding for the gp91phox for its expression in human hematopoietic cells.
An expression construct, in particular a retroviral vector suitable for gene therapy of chronic granulomatous disease, comprising said nucleic acid is as well disclosed therein. ([0027], Figure 3, [0037], [00042], SEQ ID NO.1, claims).
The query sequence SEQ ID NO:11 has 99.9 % identity (99.9 % similarity) over 1659 positions in a common overlap (range (q:s): 1-1659:55-1713) with subject CAS: 2009_108728_1105083779_ 1 (length: 1713) of EP 134.
WO 356 (Example 1; SEQ ID NO:80) teaches a method for inducing gene regulation of a target nucleic acid in a primary cell, for preventing or treating genetic disease in a subject by administering a modified single guide RNA (sgRNA). The sequence represents an IL2RG target amplicon sequence, which is used in for inducing gene regulation of a target nucleic acid in a primary cell. X-CGD is not mentioned.
According to paragraph [0013] FIGS. 2A-2C show that chemically modified sgRNAs facilitate high rates of gene disruption in primary human T cells and CD34<+>hematopoietic stem and progenitor cells (HSPCs).
The query sequence SEQ ID NO:9 has 100 % identity (100 % similarity) over 20 positions in a common overlap (range (q:s): 20-1:2-21) with subject GSN:BDH54825 (length: 212) of WO2016164356-A1 published on 2016-10-13.
In this manner, WO 356 discloses the sgRNA comprising the one of SEQ ID NO:9 which guides the Cas polypeptide to the target nucleic acid.
WO 729 teaches a donor cassette comprises homology arms (HAs). The donor cassette comprises a left homology arm (left HA) and a right homology arm (right HA). The HA may comprise the sequence of SEQ ID NO:53 which is the one of SEQ ID NO: 9 of the present application. It discloses a population of genome edited cells may be useful in the treatment, chronic granulomatous disease.
The query sequence SEQ ID NO:9 has 100 % identity (100 % similarity) over 20 positions in a common overlap (range (q:s): 1-20:166-185) with subject GSN:BHR36959 (length: 290) from WO2020074729-A1 published on 2020-04-16. AAV6 IL2RG-targeting construct left homology arm DNA, SEQ ID 53.
In this way, those of ordinary skill could have applied a donor template comprising a cDNA comprising a nucleotide sequence having at least 80% identity to SEQ ID NO:11 in the manner required and in a predictable fashion for the purposes of using CRISPR CAS 9 to genetically modify the CYBB gene. As outlined above, De Ravin teaches a CRISPR CAS 9 method based on homologous recombination by editing the CYBB gene. The secondary references are added for the proposition that the recited donor template is applicable to this process. Specifically, the secondary references teach that the particular known technique using the recited polynucleotide having at least 80% identity to SEQ ID NO:11 as a donor template for CRIPR CAS 9 was recognized as part of the ordinary capabilities of one skilled in the art. In this manner, those of ordinary skill would have recognized that applying the known technique to those methods that use CRISP CAS 9, such as those described by De Ravin to edit CYBB, would have yielded predictable results. Accordingly, using a donor template having at least 80% identity to SEQ ID NO:11 to genetically modify the CYBB gene using CRISPR CAS 9 would have been prima facie obvious.
The claims have been amended to require that the sgRNA binds to the nuclease and directs it to a target sequence within exon 1 or exon 2 of the CYBB gene, whereupon the nuclease cleaves the gene at the target sequence. In this regard, Applicant argues that none of the applied references teaches or suggests the targeted insertion of a codon-optimized CYBB cDNA at exon 1 or exon 2.
However, Sweeney teaches that (CRISPR)/Cas9 was utilized for targeted knockout of mouse Cybb on the X-chromosome by microinjection of NSG mouse zygotes with Cas9 mRNA and CRISPR single-guide RNA targeting Cybb exon 1 or exon 3. Therefore, mutations in the recited exons were known and their targeting for (CRISPR)/Cas9 correction/therapy was known. Therefore, insertion of a codon-optimized CYBB cDNA at exon 1 or exon 2 would have been prima facie obvious.
THIS ACTION IS MADE FINAL. 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.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KARL J PUTTLITZ whose telephone number is (571)272-0645. The examiner can normally be reached on Monday to Friday from 9 a.m. to 5 p.m.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Gregory Emch, can be reached at telephone number 571-272-8149. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KARL J PUTTLITZ/ Primary Examiner, Art Unit 1646