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 .
Response to Amendment/Status of Claims
Receipt of Arguments/Remarks filed on 05/04/2026 is acknowledged. Claims 121 and 133 were amended. Claims 119,121-131,133,136-148 are pending. Claims 119 and 121-129 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 treated without traverse in the reply filed on 01/08/2025. Claims 130,131,133 and 136-148 are directed to the elected invention and are under examination.
Maintained Rejections
Claim Rejections - 35 USC § 103
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 130 and 131 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2014186585 (‘585) in view of Guo et al. (Journal of Human Genetics (2010) 55, 571-576) as evidenced by NCBI Reference Sequence NM_000539.3.
Regarding claims 130-131, ‘585 teaches methods of modifying an endogenous gene which may be a rhodopsin (RHO) gene, comprising administering to the cell a first nucleic acid molecule comprising a single guide RNA that recognizes a target site in the endogenous gene and a second nucleic acid that encodes a functional domain which associates with the sgRNA on the target site, thereby modifying the endogenous gene (paragraph 0022). ‘585 teaches a CRISPR/Cas system that binds to a target site in a region of interest in an endogenous gene wherein the CRISPR/Cas system comprising one or more engineered sgRNAs that recognize the target gene and a functional domain (e.g. a nuclease domain) (paragraphs 0016,0018), and teach the Cas nucleases are Cas9 nucleases (paragraphs 0025-0027). ‘585 teaches the methods and compositions of the invention may be used to disrupt a RHO allele with a CRISPR/Cas system where the single guide RNA comprises sequences to target a human RHO gene, and that targeting specific locations are useful for gene correction, and preferred target locations include exon 1 and exon 5 (paragraph 0070).
‘585 teaches guide RNAs for use with the CRISPR/Cas system and that cells of interest are contacted with the sgRNAs in Table 1 (paragraph 0221, pages 81-82). ‘585 teaches sgRNA sequences targeting human RHO of SEQ ID NOs: 184-186 and which are 23 nucleotides in length (Table 2, page 84).
‘585 does not teach wherein the first targeting domain of the first gRNA molecule comprises a sequence that is the same as, or differs by no more than 3 nucleotides from a sequence selected from the group consisting of SEQ ID NOs: 100-103.
However, before the effective filing date, Guo et al. taught the mRNA sequence of the rhodopsin gene was publicly available as evidenced by NCBI Reference Sequence NM_000539.3. The human RHO gene sequence (NM_000539.3) was taught by Guo et al. (page 63, left column) more than one year prior to the effective filing date of the instant application. The human RHO mRNA sequence of NM_000539.3 is shown below.
PNG
media_image1.png
804
518
media_image1.png
Greyscale
As seen in the alignment below, a BLAST of instant SEQ ID:100 aligns with nucleotides 74-95 of the RHO mRNA sequence of NM_000539.3.
PNG
media_image2.png
216
478
media_image2.png
Greyscale
Alignment of instant SEQ ID NO: 101 to the sequence of NM_000539.3 (Qy is instant SEQ ID NO: 101, Db is NM_000539.3):
PNG
media_image3.png
69
307
media_image3.png
Greyscale
Alignment of instant SEQ ID NO: 102 to the sequence of NM_000539.3 (Qy is instant SEQ ID NO: 102, Db is NM_000539.3):
PNG
media_image4.png
82
304
media_image4.png
Greyscale
Alignment of instant SEQ ID NO: 103 to the sequence of NM_000539.3 (Qy is instant SEQ ID NO: 103, Db is NM_000539.3):
PNG
media_image5.png
76
304
media_image5.png
Greyscale
As shown above, instant SEQ ID NOs: 100-103 target different regions of the RHO sequence.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date, to choose any of the 22 nucleotide regions of the target RHO gene sequence and to produce gRNA target sequences that target these nucleotide regions to arrive at the gRNA sequences of instant SEQ ID NOs: 100-103 for use in the method of altering a cell with a reasonable expectation of success. There would be a reasonable expectation of success, because Guo et al. teach the RHO mRNA sequence was known before the effective filing date, and alignment of the instant sequences with the RHO mRNA sequences is shown to align with different regions of the RHO gene. One of ordinary skill in the art would have been motivated to provide a guide RNA of any of SEQ ID NOs: 100-103 for use in the method of ‘585, because ‘585 teaches the methods and compositions of the invention may be used to disrupt a RHO allele with a CRISPR/Cas system where the single guide RNA comprises sequences to target a human RHO gene, and that targeting specific locations are useful for gene correction, (paragraph 0070) and would make obvious the limitations of claims 130 and 131.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date.
Response to Arguments
Applicant's arguments filed, 05/04/2026 have been fully considered but they are not persuasive.
Applicant cites In re Baird and MPEP 2144.08 and argues on pages 6-7 of the response, that 585’s three rhodopsin gRNAs of SEQ ID NOs: 184-186 are 23 nucleotide in length and were designed for use with S. pyogenes Cas9 (SpCas9) which recognizes an NGG PAM, while the claimed SEQ ID NOs: 100-103 are 22 nucleotides in length and were designed for use with S. aureus Cas9 (SaCas9) which recognizes an NNGRRT PAM (See WO 2020/176552 at 46:19-21, Table 1). The RHO mRNA sequence (NM_000539.3) is 2768 nucleotide long, and ‘585 does not design, disclose or test any SaCas9 compatible gRNAs targeting the RHO gene. Applicant argues because SpCas9 and SaCas9 recognize distinct PAMs, the candidate target sites in the RHO available to a person of ordinary skill designing for each enzyme are defined by different flanking sequence requirements and by mutually exclusive PAM requirements. A person of ordinary skill starting from ‘585’s SpCas9 based system would not arrive at the claimed SaCas9-compatible sequences and ‘585 provides no guidance for selecting specific claimed sequences from among these candidates. Applicant argues Guo et al. pertains to linkage analysis and mutation screening study that identified an RHO mutation in a Chinese Bai family with autosomal dominant retinitis pigmentosa and provides no teaching regarding gRNA design or CRISPR/Cas9 systems. Applicant argues the mere existence of a gene sequence does not render obvious any particular gRNA targeting domain sequence directed to that gene.
This is not found persuasive. Instant claims 130 and 141 only require that (b) is a nucleic acid comprising a sequence that encodes an RNA-guided nuclease molecule, which can be any RNA-guided nuclease molecule, and claims 131,133,136-140,142-148 only require a Cas9 molecule, which can be any Cas9 molecule. The instant claims do not recite or require an S. aureus Cas9 (SaCas9), and do not recite any specific PAM sequences or requirements. Paragraph 0221 of ‘585 cited in the rejection as well as in Applicant’s arguments states that Table 1 shows a series of sgRNAs for use with the CRISPR/Cas system. Paragraph 0144 of ‘585 discloses that Cas9 orthologs are found in 347 species of bacteria, and that the term “Cas9” refers to an RNA guided DNA nuclease comprising a DNA binding domain and two nuclease domains, where the gene encoding the Cas9 may be derived from any suitable bacteria. ‘585 also teaches that alternative PAM sequences may be utilized, and that in addition to the S. pyogenes encoded Cas9 PAM sequences, other PAM sequences can be used that are specific for Cas9 proteins from other bacterial sources (paragraph 0172). It is also noted that page 47 of the instant specifications states that RNA guided nucleases suitable for use in the context of the methods, strategies and treatment modalities herein are listed in Table 4 and the methods, compositions and treatment modalities disclosed herein can, in some embodiments, make use of any combination of RNA-guided nucleases disclosed herein. Table 4 includes SpCas9 and SaCas9 and their respective PAM sequences and lists other types of RNA-guided nucleases as well. Regarding Applicant’s arguments to Guo et al., Guo et al. was cited to show that the mRNA sequence of RHO was publicly available before the effective filing date for one of ordinary skill in the art to be able to design gRNAs targeting RHO.
Applicant argues on pages 7-8, that ‘585 didn’t perform an independent gRNA screen and that the gRNAs were derived from pre-existing zinc finger nuclease target sites by identifying a G[N20]GG motif overlapping the ZFN spacer (paragraph 0221), and the gRNAs are constrained by the locations of pre-existing ZFN sites and do not reflect any independent analysis of optimal gRNA target sites. In contrast, the instant SEQ ID NOs: 100-103 were identified by an independent empirical screen of around 430 RHO-targeting gRNAs, and mapping analysis confirms that the three RHO gRNAs of ‘585 of SEQ ID NOs: 184-186 target different, non-overlapping regions of the RHO gene than the instant claimed sequences and therefore ‘585 directs a person of ordinary skill to entirely different target sites than those recited in the claims.
This is not found persuasive. Regarding Applicant’s argument that ‘585 did not perform a gRNA screen or analyze optimal gRNA target sites, the rejection is made under 103 and does not need to exemplify all embodiments, only suggest. “Disclosed examples and preferred embodiments do not constitute a teaching away from the broader disclosure or non-preferred embodiment.” In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). MPEP 2123. In addition, regarding Applicant’s argument about the sequences of ‘585 targeting different regions of the RHO gene than the instant claimed sequences, this is not found persuasive because Example 3, page 103 of the instant specification states that RHO-3 (SEQ ID NO: 102) is predicted to target Exon 1, and page 6 of spec says the RHO target position is a target position located in exon 1 or exon 2 of the RHO gene. Page 40 of the instant specification states that gRNAs in tier 1 were selected based on cutting in exon 1 and exon 2 of the RHO gene, and Table 1 provides targeting domains for an exon 1 or exon 2 RHO target position in the RHO gene, and Table 1 includes SEQ ID NOs: 100-103. Paragraph 0070 of ‘585 teaches that preferred target locations include exon 1 and exon 5. Therefore, ‘585 teaches targeting exon 1, which is also the region that the instant claimed sequences (instant RHO-3 of SEQ ID NO: 102) is predicted to target.
Applicant argues on page 8 that the guidance in ‘585 regarding where to target the RHO gene is tied to facilitating correction of the P23H, Q64X and Q344X point mutations and that preferred target locations include exon 1 and exon 5 (paragraph 0070 of ‘585), and therefore a POSA reading ‘585 would be directed to target sites positioned for correction of those mutations, not the regions targeted by instant SEQ ID NOs: 100-103 which lie outside the coordinates ‘585 defines as preferred, and therefore ‘585 provides no motivation to select the claimed sequences from the broader universe of possible RHO-targeting gRNAs. e region that instant RHO-3 of SEQ ID NO: 102 is predicted to target. Applicant argues on pages 8-9 that neither ‘585 nor Guo et al. identify the regions targeted by SEQ ID NOs: 100-103 as preferred or even contemplate targeting locations, and ‘585 points elsewhere and Guo et al. provides only the RHO sequence itself. Applicant cites MPEP 2145 regarding impermissible hindsight.
This is not found persuasive. As discussed above, Example 3, page 103 of the instant specification states that RHO-3 (SEQ ID NO: 102) is predicted to target Exon 1, and page 6 of spec says the RHO target position is a target position located in exon 1 or exon 2 of the RHO gene. Paragraph 0070 of ‘585 teaches that preferred target locations include exon 1 and exon 5. Therefore, ‘585 teaches targeting exon 1, which is also the region that instant RHO-3 of SEQ ID NO: 102 is predicted to target, and therefore one of ordinary skill in the art would have had a reasonable expectation of success of arriving at the instant claimed sequences, particularly SEQ ID NO: 102 which targets exon 1 based on the teachings of ‘585 regarding targeting exon 1. Guo et al. was cited to show that the mRNA sequence of RHO was publicly available before the effective filing date for one of ordinary skill in the art to be able to design gRNAs targeting RHO. Obviousness does not require absolute predictability, however, at least some degree of predictability is required. Evidence showing there was no reasonable expectation of success may support a conclusion of nonobviousness. NOTE: MPEP 2143.02. In response to applicants argument regarding improper hindsight reasoning it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based on hindsight reasoning, but so long as it takes into account only knowledge which was within the level of ordinary skill in the art at the time the claimed invention was made and does not include knowledge gleaned only from applicant’s disclosure, such a reconstruction is proper." In re McLaughlin, 443 F.2d 1392, 1395, 170 USPQ 209, 212 (CCPA 1971).
Therefore, the rejection is maintained.
Claims 133 and 136-148 are rejected under 35 U.S.C. 103 as being unpatentable over ‘585 and Guo et al. as evidenced by NCBI Reference Sequence NM_000539.3 as applied to claims 130 and 131 above, and further in view of Tsai et al. (Ophthalmol. 125(9): 1421-1430 September 2018), cited in prior office action.
The teachings of ‘585 and Guo et al. as evidenced by NCBI Ref. Seq. NM_000539.3 as applicable to claims 130 and 131 are described above.
In addition, ‘585 teaches “In relation to RP, more than 80 mutations in the rhodopsin gene have been identified that account for 30% of all Autosomal Dominant Retinitis Pigmentosa (ADRP) in humans. Three point mutations in the human rhodopsin gene (leading to P23H, Q64X and Q344X in the protein sequence) are known to cause ADRP in humans. The P23H mutation is the most common rhodopsin mutation in the United States. Due to problems with protein folding, P23H rhodopsin only partially reconstitutes with retinal in vitro, and mutant rhodopsin expressed in transgenics causes retinal degeneration. Thus, the methods and compositions of the invention may be used to disrupt a RHO allele with a CRISPR/Cas system where the single guide RNA comprises sequences to target a human RHO gene (paragraph 0070).
‘585 and Guo et al. as evidenced by NCBI Ref. Seq. NM_000539.3 do not teach wherein the nucleic acid of (a) or (b) further comprises (c) a RHO cDNA molecule, and do not teach a method of altering a retinal cell in vivo comprising delivering to the cell via subretinal injection an AAV vector comprising the nucleic acid sequence that encodes a first gRNA molecule and a nucleic acid comprising a sequence that encodes an RNA-guided nuclease molecule operably linked to a rod-specific promoter.
However, before the effective filing date, Tsai et al. teach an “ablate and replace” strategy that destroys expression of all endogenous chromosomal Rho genes in a mutation independent manner using an improved CRISPR/Cas9 based gene ablation technique, and enables expression of wild-type protein through exogenous cDNA (page 3, second paragraph). Tsai et al. teach using an expression cassette, AAV-GR, which comprises two gRNA expressing cassettes and an mRho promoter-driven hRHO cDNA expressing cassette cloned into a vector, and an AAV-Cas9 expression cassette (page 3), in which the gRNAs target sequences in exon 1 of mouse Rho (Results pg 5). Tsai et al. teach all components were cloned into two AAV vectors, where Cas9 was packaged into one vector and the dual gRNA expression cassettes and human RHO cDNA driven by an mRho promoter were cloned in another AAV vector, and gene ablation could only occur in any cells that took up both vectors, while gene replacement could occur in any rod photoreceptors that took up just the hRHO cDNA containing vector, and teach subretinal injection into the eye (page 6). Tsai et al. teach that the in vivo AAVs-Cas9+GR-mediated gene ablation leads to decreased endogenous mRho levels in photoreceptors and rod cells, and that dual AAV ablate-and-replace combination system has therapeutic efficacy in treating dominant retinal degenerative disorders (page 7), and the ablate-and-replace combination leads to significantly greater survival of functioning photoreceptors, and is mutation-independent (page 8). Tsai et al. teach gene replacement driven by a native Rho promoter has higher safety and durability in patients compared to using a ubiquitous promoter (page 9, first paragraph).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date, to have modified the nucleic acid molecule used in the method of ‘585 and Guo et al. as evidenced by NM_000539.3, with the teachings of Tsai et al. regarding the RHO cDNA and arrangement of the AAV vectors to arrive at the instant claims with a reasonable expectation of success, as it would have amounted to applying a known technique (the method of Tsai et al.) to a known method (the method of ‘585) ready for improvement to yield predictable results. One of ordinary skill in the art would have been motivated to modify the nucleic acid molecule used in the method of ‘585 and Guo et al. as evidenced by NM_000539.3, to comprise an RHO cDNA molecule in the nucleic acid molecule comprising the sequence encoding the gRNA molecule and that the nucleic acid molecules are AAV vectors, and that the cell is a retinal cell, because Tsai et al. teach an ablate-and-replace method using one AAV vector encoding Cas9 and another AAV vector encoding gRNA and RHO cDNA, and that the ablate-and-replace combination leads to significantly greater survival of functioning photoreceptors, and is mutation-independent, and has therapeutic efficacy in treating dominant retinal degenerative disorders and would make obvious the limitations of claims 133 and 136-138.
It would have been obvious to one of ordinary skill in the art before the effective filing date, to have to have modified the nucleic acid molecule used in the method of ‘585 and Guo et al. as evidenced by NM_000539.3, with the teachings of Tsai et al. to arrive at the instant claims with a reasonable expectation of success, as it would have amounted to applying a known technique (the method of Tsai et al.) to a known method (the method of ‘585) for improvement to yield predictable results. One of ordinary skill in the art would have been motivated to modify the nucleic acid molecule used in the method of ‘585 to comprise a promoter operably linked to either the RNA-guided nuclease molecule, the RHO cDNA molecule or both, and for the promoter to be a rod-specific promoter, because Tsai et al. teach two AAV vectors, where Cas9 was packaged into one vector and the dual gRNA expression cassettes and human RHO cDNA driven by an mRho promoter were cloned in another AAV vector, and that gene ablation could only occur in any cells that took up both vectors, while gene replacement could occur in any rod photoreceptors that took up just the hRHO cDNA containing vector, and would make obvious the limitations of claims 139 and 140.
It would have been obvious to use the nucleic acid molecule of ‘585 and Guo et al. as evidenced by NM_000539.3 in an in vivo method as taught by Tsai et al. to arrive at the instant claims with a reasonable expectation of success, as it would have amounted to applying a known technique (the method of Tsai et al.) to a known method (the method of ‘585) for improvement to yield predictable results. One of ordinary skill in the art would have been motivated to alter a retinal cell in vivo comprising delivering to the cell via subretinal injection an AAV vector comprising the nucleic acid molecules of ‘585 and Guo et al. as evidenced by NM_000539.3, because ‘585 teaches the methods and compositions of the invention may be used to disrupt a RHO allele with a CRISPR/Cas system where the single guide RNA comprises sequences to target a human RHO gene, and that targeting specific locations are useful for gene correction, (paragraph 0070). In addition, Tsai et al. teach two AAV vectors, where Cas9 was packaged into one vector and the dual gRNA expression cassettes and human RHO cDNA driven by an mRho promoter were cloned in another AAV vector subretinal injection into the eye (page 6). Tsai et al. teach that the in vivo AAVs-Cas9+GR-mediated gene ablation leads to decreased endogenous mRho levels in photoreceptors and rod cells, and that dual AAV ablate-and-replace combination system has therapeutic efficacy in treating dominant retinal degenerative disorders (page 7), and the ablate-and-replace combination leads to significantly greater survival of functioning photoreceptors, and is mutation-independent (page 8). One of ordinary skill in the art would be motivated to carry out the method wherein a RHO cDNA is operably linked to a rod-specific promoter because Tsai et al. teach gene replacement driven by a native Rho promoter has higher safety and durability in patients compared to using a ubiquitous promoter (page 9, first paragraph).
Accordingly, the limitations of claims 140-148 would have been prima facie obvious to one of ordinary skill in the art before the effective filing date.
Response to Arguments
Applicant's arguments filed 05/04/2026 have been fully considered but they are not persuasive.
Applicant argues on page 9 of response that this rejection depends on the rejection of claims 130-131 and should be withdrawn for the reasons set forth above. In addition, Tsai et al. does not cure the deficiencies of ‘585 and Guo et al., as Tsai et al. designed gRNAs to specifically target mouse Rho, not human RHO, using S. pyogenes Cas9 which recognizes an NGG PAM and its guide RNA sequences are different from and PAM-incompatible with the instant claimed sequences.
This is not found persuasive. The Examiner has responded to the arguments regarding ‘585 and Guo et al. above. In addition, the Examiner has responded to the arguments regarding S. pyrogenes gRNAs that recognize different PAM sequences above, and reiterates that the instant claims do not recite or require a specific Cas9. In addition, Tsai et al. was cited for teaching that all components were cloned into two AAV vectors, where Cas9 was packaged into one vector and the dual gRNA expression cassettes and human RHO cDNA, and therefore taught the limitations of a RHO complementary DNA molecule, rather than suggesting that the mouse RHO gRNAs of Tsai et al. be used. While Tsai et al. taught the gRNAs as targeting mouse RHO, it is noted that the gRNAs of Tsai et al. were taught as targeting sequences in exon 1 of mouse Rho (Results pg 5).
Therefore, the rejection is maintained.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 130,131,133 and 136-148 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 183-188 of copending Application No. 18/555,716 (‘716) (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because instant claim 130 recites a method of altering a cell in vitro or ex vivo comprising contacting the cell with (a) a nucleic acid comprising a sequence that encodes a first gRNA molecule comprising a first targeting domain sequence that is complementary to a first target domain sequence of a RHO gene wherein the first targeting domain comprises a sequence that is the same as or differs by no more than 3 nucleotides from a sequence selected from the group consisting of SEQ ID NOs: 100-103 and (b) a nucleic acid comprising a sequence that encodes an RNA-guided nuclease molecule and instant claim 131 recites the RNA-guided nuclease is a Cas9 molecule. Claim 183 of ‘716 recites a method of altering a cell comprising contacting the cell with a pharmaceutical composition comprising a first nucleic acid comprising a sequence encoding an RNA-guided nuclease; and a second nucleic acid comprising a sequence encoding a first guide RNA comprising a first targeting domain that is complementary to a target domain in the RHO gene and a RHO complementary DNA, and claim 184 of ‘716 recites SEQ ID NOs: 100-502 which are the same sequences as SEQ ID NOs: 100-103 recited in claim 130 of ‘716.
Instant claims 133 and 143 recite the nucleic acid of (a) or (b) further comprises (c) a RHO cDNA molecule and instant claims 136 and 144 recite that (b) is present in the first nucleic acid molecule and (a) and (c) are present on the second nucleic acid molecule, while claim 183 of ‘716 as described above recites the RHO cDNA is in the second nucleic comprising the targeting domain complementary to a target domain in the RHO gene. Both instant claims 137 and 146 and claim 186 of ‘716 recite viral vectors.
Instant claims 139-140 and 145 recite the sequence encoding the RNA-guided nuclease, the RHO cDNA molecule, or both are operably linked to a promoter, and wherein the promoter is a rod-specific promoter, while claim 187 of ‘716 recites the first nucleic acid comprises a promoter operably linked to the sequence encoding the RNA-guided nuclease, and claim 188 recites the second nucleic acid comprises a promoter linked to the RHO cDNA.
Therefore the instant methods of claims 130-133 and 136-148 are not patentably distinct from the methods of claims 183-188 of ‘716.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant requests the provisional double patenting rejection be held in abeyance until allowable subject matter is identified in the present application, and reserves the right to file a terminal disclaimer if and when appropriate.
. Therefore, the rejection is maintained.
Conclusion
Claims 130,131,133 and 136-148 are rejected.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to STEPHANIE L SULLIVAN whose telephone number is (703)756-4671. The examiner can normally be reached Monday-Friday, 7:30-3:30 EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Ram R Shukla can be reached on 571-272-0735. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/STEPHANIE L SULLIVAN/Examiner, Art Unit 1635
/ABIGAIL VANHORN/Primary Examiner, Art Unit 1636
Prosecution Insights