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
Applicant’s claim to priority from International Application No. PCT/US2021/032185 filed 05/13/2021 and from Provisional Application No. 63/025,258 filed 05/15/2020 is hereby acknowledged.
Election/Restrictions
Applicant’s election without traverse of Species in the reply filed on 12/08/2025 is acknowledged. The election of Species is as follow:
Species Group A (at claims 4 and 14): a human ADAR or ADAR domain,
(1) A human ADAR1.
Species Group B (at claim 16): a OTOF polynucleotide encoding an OTOF protein comprising a pathogenic amino acid comprising:
(1) a glutamine at position 1939.
Species Group C (at claims 19, 124 and 145-147): a guide oligonucleotide comprising the structure
[Am]-X1-X2-X3-[Bn]
(1) Applicant elected 35 as number for “m”.
(2) Applicant elected 12 as number for “n”.
(3) Applicant elected Formula 1 for X1, with R1 is fluoro and N= C.
(4) Applicant elected Formula 1 for X2, with R1 is fluoro and N= C.
(5) Applicant elected Formula 1 for X3, with R1 is fluoro and N= G.
(6) Applicant elected a specific nuclease-resistant modification pattern where A and B sugars are fully modified with 2’-O-Methyl and internucleotide phosphorothioate (PS) linkage modifications at the two terminal ends, 5’ and 3’, comprising four PS linkages.
Applicant identifies that at least claims 1, 2, 4, 10-11, 16, 19, 124 and 145 read on the elected species.
Claims 146 and 147 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12/08/2025.
Applicant is reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
Application Status
This Application is a CON of PCT/US2021/032185 filed 05/13/2021.
Preliminary claim amendments are hereby acknowledged. Claims 2, 4, 13-14, 16, 19, 124 and 145-147 are currently amended. Claims 3, 5-9, 15, 17-18, 20-123 and 125-144 are cancelled.
Claims 146 and 147 are withdrawn from further consideration, therefore, claims 1-2, 4, 10-14, 16, 19, 124 and 145 are pending and under consideration in this office action.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 11/16/2023 is hereby acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Drawings
There is no Drawing in the disclosure.
Specification
Abstract: The abstract of the disclosure is objected to because of the following informality: The Abstract recites : “The present invention reates to methods and compositions…”. It should read “The present invention relates to methods and compositions…”. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Specification: The use of the terms “Droplet Digital PCR”, “Illumina”, “Qiagen”, “Eppendorf”, “Applied Biosystems”, “Cepheid” (page 48),“RNAzol”, “PAXgene”, “PreAnalytix” (page 50), “Lipofectamine” (pages 62 and 130), which are trade names or marks used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 16 is rejected under 35 U.S.C. §112(b) or 35 U.S.C. §112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 16, it recites: “The method of claim 1, wherein the OTOF polynucleotide encodes an OTOF protein comprising a pathogenic amino acid comprising a glutamine at position 1939, an arginine at position 794, or a premature stop codon at position 829 resulting from the SNP;
wherein the adenosine to inosine alteration substitutes the pathogenic amino
acid with a wild type amino acid; and/or
wherein the wild type amino acid at position 1939 comprises an arginine, wherein
the wild type amino acid at position 794 comprises a histidine, and wherein the wild type amino acid at position 829 comprises a glutamine”.
According to the Specification, R794H is a “variant (or mutation) based on the potential change from arginine (encoded by rs80356592(G) allele) to histidine (encoded by rs80356592(A) allele) at position 794 of the OTOF protein (see page 20, lines 5-9).
Therefore, the claim is not clear whether the modification as claimed here are to produce a genetically modified animal disease model, or to correct an existing pathogenic mutation. It seems to consider an arginine at position 794 as a pathogenic amino acid that needs to be substituted to a wild type amino acid that is histidine, while the disclosure indicates the reverse.
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 1-2, 4, 14 and 16 are rejected under 35 U.S.C. §103 as being unpatentable over Liu (Liu, D.R. et al. US Patent No. 10,113,163 B2, dated October 30, 2018, with prior publication of US 2018/0073012 A1 on March 15, 2018).
Regarding claim 1, , it recites “A method of editing an OTOF polynucleotide comprising a single nucleotide polymorphism (SNP) associated with autosomal recessive non-syndromic hearing loss, the method comprising contacting the OTOF polynucleotide with a guide oligonucleotide capable of effecting an adenosine deaminase acting on RNA (ADAR)-mediated adenosine to inosine alteration of the SNP associated with autosomal recessive non-syndromic hearing loss, thereby editing the OTOF polynucleotide.”
Liu teaches fusion proteins comprising a Cas9 domain and adenosine deaminases that deaminate adenosine in DNA (see title and abstract). Liu teaches using ADAR (see column 3, lines 44-46). Liu teaches that the ADAR can be ADAR1 (see column 414, lines 8-10 and 61-64).
Liu teaches methods for treatment of a subject diagnosed with a disease associated with or caused by a point mutation that can be corrected by a DNA editing fusion protein provided. The method comprises administering to a subject having such disease an effective amount of an adenosine deaminase fusion protein that corrects the point mutation into a disease-associated gene (see column 164, lines 52-61).
Liu teaches the use of a system comprising fusion Cas9 and ADAR proteins using guide RNAs targeting SNPs in OTOF gene for correction of Non-syndromic hearing loss and autosomal recessive Deafness (see columns 337-338 in Table 2; see column 169, lines 1-2).
Regarding claim 2, Liu teaches eukaryotic cells such as Hek293T mammalian cells (see column 2, lines 10-22; column 4, lines 24-25 and 38-40). Liu teaches that the correction of mutations can be performed using the composition described for genetic defects in cells ex vivo, e.g., in cells obtained from a subject that are subsequently re-introduced into the same or another subject (see column 40, lines 20-26). Liu teaches that the subject can be a human, a vertebrate, or a non-human mammal such as a sheep, a goat, a cattle, a cat or a dog (see column 39, lines 17-25).
Regarding claim 4, Liu teaches using ADAR (see column 3, lines 44-46). Liu teaches that the ADAR can be ADAR1 (see column 414, lines 8-10 and 61-64).
Regarding claim 14, Liu teaches guide oligonucleotide sequences that comprises a nucleic acid sequence complementary to an OTOF mRNA sequence comprising the SNP associated with autosomal recessive non-syndromic hearing loss (see Table 2, columns 337-338).
Regarding claim 16, Liu teaches correcting different SNPs, more specifically, p.Gly614Glu (G614E), p.Arg794His (R794H), p.Arg1939Trp (R1939W), p.Arg1134Ter (R1134X), p.Gln940ter (Q940X) in OTOF gene , providing corresponding guide RNA molecules (see columns 337-338, Table 2).
Examiner interprets the claim as drawn to correcting of a pathogenic histidine at position 794 to revert to an arginine in view of the Specification (see page 20, lines 5-9).
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 considered and modified the systems and method of using ADAR in fusion with Cas9 effector protein as taught by Liu, and used specifically a human ADAR1 since the systems are used in human subjects, as well as the specific guide RNA molecules provided for targeting and correcting the SNP of interest in OTOF gene. One with ordinary skills in the art, specifically motivated in using a gene editing system to target OTOF gene for gene therapy of non-syndromic hearing loss patients, could have performed these modifications with a reasonable expectation of success and arrived at the claimed invention.
Claims 1-2, 4, 14 and 16 are rejected under 35 U.S.C. §103 as being unpatentable over Zhang (Zhang, F. et al. WO 2019/084062 A1; published May 2, 2019; cited in IDS filed 11/16/2023 as ref#B25).
Regarding claim 1, it recites “A method of editing an OTOF polynucleotide comprising a single nucleotide polymorphism (SNP) associated with autosomal recessive non-syndromic hearing loss, the method comprising contacting the OTOF polynucleotide with a guide oligonucleotide capable of effecting an adenosine deaminase acting on RNA (ADAR)-mediated adenosine to inosine alteration of the SNP associated with autosomal recessive non-syndromic hearing loss, thereby editing the OTOF polynucleotide.”
Zhang teaches a method of editing RNA in a targeted way, using one guide molecule and at least one adenosine deaminase protein or catalytic domain thereof (see abstract and Figure 1). Zhang teaches a guide sequence that is designed to have a non-pairing C, the RNA duplex formed between the guide sequence and the target sequence comprises an A-C mismatch, which directs the adenosine deaminase to contact and deaminate the A opposite to the non-pairing C, converting it to a Inosine (see [0146]). Zhang teaches that the mismatch is due to a pathogenic mutation/SNP present in OTOF gene (see [0671]). Zhang teaches a method, systems and compositions used to correct one or more pathogenic G-to-A or C-to-T mutations/SNPs associated with Non-syndromic hearing loss, wherein the gene is OTOF (see [0672]).
Regarding claim 2, Zhang teaches contacting the OTOF polynucleotide with the guide oligonucleotide in a cell (see [0020]). Zhang teaches that the cell can be a eukaryotic host cell, issued from pig, cow, dog or other (see [0925]-[0934]). Zhang also teaches that sequences can be optimized for expression in a eukaryote, e.g. humans, or for another eukaryote, animal or mammal (see [0130], [0195]).
Regarding claim 4, Zhang teaches that the ADAR is a human ADAR (see [00104]). Zhang teaches that the human ADAR can be hADAR1, hADAR2 or hADAR3 (see [0293]). Zhang teaches that the Cas13 protein can be fused to hADAR1 or hADAR2 (see [1014]).
Regarding claim 14, Zhang teaches that guide oligonucleotide comprises a nucleic acid sequence complementary to an OTOF mRNA sequence comprising the SNP associated with autosomal recessive non-syndromic hearing loss (see [0135], [0670], [0672]).
Regarding claim 16, Zhang teaches the Gln829Ter SNP (Q829X) in OTOF gene (see [0671]).
Zhang’s teachings are not exclusively focused on OTOF genes and non-syndromic hearing loss. However, Zhang teaches methods and compositions applicable to OTOF gene, with multiple examples of SNPs for OTOF (see [0672]) that can be targeted using the system described in Zhang’s disclosure.
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 considered and modified the systems and method of using human ADAR in fusion with Cas13 effector protein, and designed specific guide RNA for targeting OTOF gene. One with ordinary skills in the art, specifically motivated in using a gene editing system to target OTOF gene for gene therapy of non-syndromic hearing loss, could have performed this modification with a reasonable expectation of success and arrived at the claimed invention.
Claim 16 is rejected under 35 U.S.C. §103 as being unpatentable over Zhang (Zhang, F. et al. WO 2019/084062 A1; published May 2, 2019; cited in IDS filed 11/16/2023 as ref#B25), as applied to claim 1 above, and further in view of Varga ( Varga, R. et al. “ OTOF mutations revealed by genetic analysis of hearing loss families including a potential temperature sensitive auditory neuropathy allele”. Journal of Medical Genetics, Vol. 43 (2006), pp: 576-581).
The rejection of claim 1 is described above. The elements of claim 1 are rendered obvious by Zhang.
However, Zhang does not render obvious all the elements (alternatives) of claim 16, i.e.,
“The method of claim 1, wherein the OTOF polynucleotide encodes an OTOF
protein comprising a pathogenic amino acid comprising a glutamine at position 1939, an arginine at position 794, or a premature stop codon at position 829 resulting from the SNP;
wherein the adenosine to inosine alteration substitutes the pathogenic amino
acid with a wild type amino acid; and/or
wherein the wild type amino acid at position 1939 comprises an arginine, wherein
the wild type amino acid at position 794 comprises a histidine, and wherein the wild type amino acid at position 829 comprises a glutamine”.
Regarding claim 16, Examiner interprets the claim as drawn to correcting of a pathogenic histidine at position 794 to revert to an arginine in view of the Specification (see page 20, lines 5-9).
Zhang teaches the Gln829Ter SNP (Q829X) in OTOF gene (see [0671]), however, Zhang does not teaches the following SNPs: R1939Q and R794H. However, Varga teaches in Table 1, a list of mutations including R1939Q, R794H and Q829X (see page 578).
Varga teaches that these mutations are linked to Non-syndromic recessive hearing loss, Auditory neuropathy/auditory dys-synchrony as a subtype (see page 576, left and right columns). Varga also teaches that certain types of SNPs in OTOF gene are specific to families living in the USA, including R1939Q, R794H and Q829X (see Table 1).
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 substituted the gRNA designed for p.Arg1495Ter and p.Arg708Ter mutated OTOF variants, with a gRNA designed to target variants of OTOF gene that are relevant to families present in clinical trials in the USA, i.e., R1939Q, R794H and Q829X, as taught by Varga. One with ordinary skills in the art motivated in treating subjects readily available and in need of treatment, could have performed these modifications in the method of treating non-syndromic hearing loss disclosed by Zhang, with a reasonable expectation of success and arrived at the claimed invention.
Claims 10-13 are rejected under 35 U.S.C. §103 as being unpatentable over Zhang (Zhang, F. et al. WO 2019/084062 A1; published May 2, 2019; cited in IDS filed 11/16/2023 as ref#B25), in view of Varga ( Varga, R. et al. “OTOF mutations revealed by genetic analysis of hearing loss families including a potential temperature sensitive auditory neuropathy allele”. Journal of Medical Genetics, Vol. 43 (2006), pp: 576-581).
Regarding claims 10 and 11, Zhang teaches a method of editing RNA in a targeted way, using one guide molecule and at least one adenosine deaminase protein or catalytic domain thereof (see abstract and Figure 1). Zhang teaches a guide sequence that is designed to have a non-pairing C, the RNA duplex formed between the guide sequence and the target sequence comprises an A-C mismatch, which directs the adenosine deaminase to contact and deaminate the A opposite to the non-pairing C, converting it to a Inosine (see [0146]). Zhang teaches that the mismatch is due to a pathogenic mutation/SNP present in OTOF gene (see [0671]). Zhang teaches a method, systems and compositions used to correct one or more pathogenic G-to-A or C-to-T mutations/SNPs associated with Non-syndromic hearing loss, wherein the gene is OTOF (see [0672]).
Zhang teaches contacting the OTOF polynucleotide with the guide oligonucleotide in a cell (see [0020]). Zhang teaches screening for mutations after the method is applied to cells (see [0116]).
Regarding claims 11 and 12, Zhang teaches a method for treating a disease in a subject comprising administering the system described to the subject, comprising administering a cell, a population of cells, a tissue, or an organ that comprise the system described to the subject (see claims 113-114).
Zhang also teaches that the delivery of the system can be performed indirectly via cell derived exosomes, the exosomes can be introduced to monocytes and lymphocytes isolated from peripheral blood of healthy donors. Zhang also teaches that the exosomes containing the CRISPR Cas system may be introduced autologously into a human (see [0581]). Zhang also teaches that the treatment can be administered into patients undergoing an immunosuppressive treatment, the cells or population of cells, may be made resistant to at least one immunosuppressive agent, and injected, transfused or implanted (see [0632]-[0634]).
Zhang teaches adoptive therapies combined with genome editing, comprising allogeneic lymphocyte infusions, stem cell transplantation (see [0636]-[0640]).
Regarding claim 13, Zhang also teaches human as subject (see [0614]). Zhang defines the terms “subject”, “individual: and “patient” as interchangeable, referring to a vertebrate, preferably a mammal, more preferably a human (see [0130]).
However, Zhang does not teach “identifying a subject with a single nucleotide polymorphism (SNP) associated with autosomal recessive non-syndromic hearing loss in an OTOF polynucleotide”.
However, Varga teaches a method of screening subjects for presence of SNPs using a mutation detection enhancement (MDE) method comprising PCR (see page 577, left column, “Genotyping and mutation screening” section”).
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 method of correcting a pathogenic SNP causing non-syndromic hearing loss using a systems comprising a fusion Cas13 and human ADAR, and a specifically designed guide RNA complementary to OTOF mRNA, as taught by Zhang, with a method of screening for SNPs in the OTOF gene to identify subjects presenting with the disease as taught by Varga. One with ordinary skills in the art motivated in identifying specifically subjects that would benefit from targeted gene editing of OTOF gene, having one specific SNP, could have performed this modification with a reasonable expectation of success and arrived at the claimed invention.
Claims 19, 124 and 145 are rejected under 35 U.S.C. §103 as being unpatentable over Zhang (Zhang, F. et al. WO 2019/084062 A1; published May 2, 2019; cited in IDS filed 11/16/2023 as ref#B25), as applied to claim 1 above, and further in view of Turunen (Turunen, J.J. et al. US Patent No. 10,941,402 B2 dated March 9, 2021; benefitting from priority of PCT/EP2017/071912, filed August 31, 2017 and published March 8, 2018).
The rejection of claim 1 is described above.
Zhang renders elements of claim 1 obvious.
Regarding claims 19, 124 and 145, Zhang teaches that the guide comprises one or more non-naturally occurring nucleotide or nucleotide analog, such a nucleotide with phosphorothioate linkage, a locked nucleic acid (LNA) nucleotide, comprising a methylene bridge between 2’ and 4; carbons of the ribose ring, or bridged nucleic acids (BNA). Zhang further teaches that examples of guide RNA chemical modifications include without limitation, incorporation of 2’-O-methyl, 2’-O-methyl 3’-phosphorothioate, S-constrained ethyl (cEt), or 2’-O-methyl 3’ thioPACE at one or more terminal nucleotides (see [0225]).
However, Zhang does not teach the specific chemical modifications as claimed in claims 19, 124 and 145, i.e. with the formula [Am]-X1-X2-X3-[Bn]
(1) with 35 as number for “m”.
(2) with 12 as number for “n”.
(3) with Formula 1 for X1, with R1 is fluoro and N= C.
(4) with Formula 1 for X2, with R1 is fluoro and N= C.
(5) with Formula 1 for X3, with R1 is fluoro and N= G.
Formula 1 being the following:
PNG
media_image1.png
133
112
media_image1.png
Greyscale
(6) with a specific nuclease-resistant modification pattern where A and B sugars are fully modified with 2’-O-Methyl and internucleotide phosphorothioate (PS) linkage modifications at the two terminal ends, 5’ and 3’, comprising four PS linkages.
However, Turunen teaches chemically modified single-stranded RNA-editing oligonucleotides (AONs) (see title and abstract). Turunen teaches AONs’ structures that are highly specific for ADAR proteins binding and activity. Turunen teaches the creation of antisense oligonucleotides comprising a “guide RNA” part that is complementary to the target sequence for editing, fused to a boxB portion for sequence specific recognition by the N-domain deaminase fusion protein (see column 2, lines 13-17).
Turunen claims a generic AON such as: “An antisense oligonucleotide (AON) capable of forming a double stranded complex with a target RNA sequence in a cell for the deamination of a target adenosine in the target RNA sequence by an ADAR enzyme present in the cell, wherein (i) the AON comprises a Central Triplet of 3 sequential nucleotides, (ii) the nucleotide directly opposite the target adenosine is the middle nucleotide of the Central Triplet, (iii) the middle nucleotide of the Central Triplet is a
cytidine, (iv) 1, 2 or 3 nucleotides in the Central Triplet comprise a sugar modification and/or a base modification to render the AON more stable and/or more effective in inducing deamination of the target adenosine, (v) the AON does not comprise a 5'-terminal O6-benzylguanosine, (vi) the AON is not covalently linked to a SNAP-tag domain, (vii) the middle nucleotide does not have a 2'-O-methyl modification, and (viii) the AON does not comprise a portion that is capable of forming an intramolecular stem-loop structure that is capable of binding a mammalian ADAR enzyme” (see columns 53-55, claim 1).
Turunen teaches a central triplet of 3 sequential nucleotides (ZXY) wherein 1, 2 or 3 nucleotides comprise a sugar modification and/or a base modification (see column 4, lines 8-23; see figures 1 and 2). Turunen teaches a nucleotide in the middle of the central triplet that is a cytidine (see claim 1, columns 53-54).
Turunen also teaches an oligonucleotide wherein each nucleotide comprised a 2’-O-methyl modification, with 2’O-methyl-modified phosphorothioate nucleotides at the 5’- and 3’- terminal for stability (see column 3, lines 1-7).
Turunen also teaches that the preferred embodiment is an AON showing high stability, and that has DNA nucleotides, 2’-fluoro modification as well as phosphorothioate linkages within the central triplet (see column 40, lines 38-42). Turunen teaches AONs with sugar modifications that can be DNA, unlocked nucleic acid (UNA) and 2’-fluororibose (see column 55, claim 4).
Turunen teaches AONs “wherein the base modification is selected from the group consisting of 2-aminopurine, 2,6-diaminopurine, 3-deazaadenosine, 7-deazaadenosine, 7-methyladenosine, 8-azidoadenosine, 8-methyladenosine, 5-hydroxymethylcytosine, 5-methylcytidine, Pyrrolocytidine, 7-aminomethyl-7-deazaguanosine, 7-deazaguanosine, 7-methylguanosine, 8-aza-7-deazaguanosine, thienoguanosine, inosine, 4-thio-uridine, 5-methoxyuridine, dihydrouridine, and pseudouridine” (see column 55, claim 7).
Turunen also teaches examples of AONs with 4 terminal nucleotides at 5’ and 3’ end modified with phosphorothioate linkages (see Figure 2). As a general rule, Turunen teaches AONs that comprise 2, 3, 4, 5 or 6 terminal nucleotides of the 5’ and 3’ terminus linked with phosphorothioate linkages (see column 55, claim 6,).
Turunen also teaches AONs, that have an A and B portions with a central triplet (according to the formula [Am]-X1-X2-X3-[Bn]), that are longer than 10 nucleotides and shorter than 100 nucleotides (see column 55, claim 10).
Turunen shows in Figure 2, a specific example of AON with claimed modifications, wherein m is 35 and n is 12 (according to the formula [Am]-X1-X2-X3-[Bn]) (see ADAR65-25 and ADAR65-26, figure 2). ADAR65-26 is an AON wherein m is 35 and n is 12, having a CCA as central triplet, and having the 4 terminal nucleotides in 5’ and 3’ modified with phosphorothioate linkages. Turunen also shows that in the triple YXZ, X is invariably a cytidine, and Z can be a thienoguanosine or 8-aza-7-deazaguanosine or 7-methylguanosine (see Figure 2).
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 Zhang and Turunen and designed AONs with optimum efficacy when using a gene editing system comprising an ADAR fusion protein. One with ordinary skills in the art, motivated in obtaining an efficient gene editing system using guide molecule targeting the SNPs in OTOF gene using and ADAR fusion protein as taught by Zhang, could have modified the guide molecule using the teachings of Turunen and apply the rules for modifications adapted to ADAR proteins, as optimized by Turunen. Turunen teaches adequate lengths for the oligonucleotides ranging from 10 to 100 nucleotides, with specific examples using an “m” and “n” (according to the formula [Am]-X1-X2-X3-[Bn]) of 35 and 12, and using the same 5’ and 3’ terminal nucleotides phosphorothioate modifications, and using nucleotides modified with 2’-O-methyl modifications except on the invariable middle cytidine in the central triplet, as taught by Turunen. One with ordinary skills in the art could have performed these modifications with a reasonable expectation of success and arrived at the claimed invention.
Double Patenting
The non-statutory 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 non-statutory 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 non-statutory 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 non-statutory 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.
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Claims 1-2, 4, 19, 124 and 145 are rejected on the ground of non-statutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 11,453,878 B2, in view of Liu (Liu, D.R. et al. US Patent No. 10,113,163 B2, dated October 30, 2018, with prior publication of US 2018/0073012 A1 on March 15, 2018).
Regarding claims 1-2, 4, 19, 124 and 145, claims 1-18 of USPAT’878 teaches all the limitations described in the claims 19, 124 and 145 for designing a guide RNA molecule according to the formula [Am]-X1-X2-X3-[Bn] wherein X has a formula I-IV (corresponding to formulas XII-XV in instant claim 19). Claims 1-18 of USPAT’878 are drawn to method of editing using deamination of an adenosine in an mRNA, the method comprising contacting an oligonucleotide with a cell. Therefore the claims 1-18 of USPAT’878 are generic and encompass species of formula [Am]-X1-X2-X3-[Bn]) claimed in the instant application. The claimed method being a method of treating a disorder in a subject in need thereof; see claims of USPAT’131 below:
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USPAT’878 does not teach specifically a method of treating Non-syndromic hearing loss/ autosomal recessive deafness due to SNPs in OTOF gene. However, Liu teaches using ADAR fusion protein and specific guide RNAs targeting specific SNPs in OTOF gene (see columns 337-338, Table 2).
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 USPAT’878 and Liu and designed AONs with optimum efficacy when using a gene editing system comprising an ADAR fusion protein. One with ordinary skills in the art, motivated in obtaining an efficient gene editing system using guide molecule targeting the SNPs in OTOF gene using and ADAR fusion protein as taught by Liu, could have modified the guide molecules in Table 2 (columns 337-338) and apply the rules for modifications adapted to ADAR proteins, as optimized by USPAT’878 according to the formula [Am]-X1-X2-X3-[Bn], as taught by USPAT’878. One with ordinary skills in the art could have performed these modifications with a reasonable expectation of success and arrived at the claimed invention.
Claims 1-2, 4, 19, 124 and 145 are rejected on the ground of non-statutory double patenting as being unpatentable over claims 1-24 and 26 of U.S. Patent No. 12,031,131 B2, in view of Liu (Liu, D.R. et al. US Patent No. 10,113,163 B2, dated October 30, 2018, with prior publication of US 2018/0073012 A1 on March 15, 2018).
Regarding claims 1-2, 4, 19, 124 and 145, claims 1-22 of USPAT’131 teaches all the limitations described in the claims 19, 124 and 145 for designing a guide RNA molecule according to according to the formula [Am]-X1-X2-X3-[Bn] and wherein X has the formula II (formula XIII in claim 19). Claims 23-24 and 26 of USPAT’131 are drawn to method of editing using deamination of an adenosine in an mRNA, the method comprising contacting the oligonucleotide of claim 1 with a cell. Therefore the claims 1-24 and 26 of USPAT’131 are generic and encompass species of formula II claimed in the instant application. The claimed method being a method of treating a disorder in a subject in need thereof; see claims of USPAT’131 below:
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USPAT’131 does not teach specifically a method of treating Non-syndromic hearing loss/ autosomal recessive deafness due to SNPs in OTOF gene. However, Liu teaches using ADAR fusion protein and specific guide RNAs targeting specific SNPs in OTOF gene (see columns 337-338, Table 2).
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 USPAT’131 and Liu and designed AONs with optimum efficacy when using a gene editing system comprising an ADAR fusion protein. One with ordinary skills in the art, motivated in obtaining an efficient gene editing system using guide molecule targeting the SNPs in OTOF gene using and ADAR fusion protein as taught by Liu, could have modified the guide molecules in Table 2 (columns 337-338) and apply the rules for modifications adapted to ADAR proteins, as optimized by USPAT’131 according to the formula [Am]-X1-X2-X3-[Bn] and formula II, as taught by USPAT’131. One with ordinary skills in the art could have performed these modifications with a reasonable expectation of success and arrived at the claimed invention.
Claims 1-2, 4, 19, 124 and 145 are rejected on the ground of non-statutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 12,448,620 B2, in view of Liu (Liu, D.R. et al. US Patent No. 10,113,163 B2, dated October 30, 2018, with prior publication of US 2018/0073012 A1 on March 15, 2018).
Regarding claims 1-2, 4, 19, 124 and 145, claims 1-18 of USPAT’620 teaches all the limitations described in the claims 19, 124 and 145 for designing a guide RNA molecule according to the formula [Am]-X1-X2-X3-[Bn] and wherein X has the formula II (formula XIII in claim 19). Claims 19-20 of USPAT’620 are drawn to method of editing using deamination of an adenosine in an mRNA, the method comprising contacting the oligonucleotide of claim 1 with a cell. Therefore the claims 1-20 of USPAT’620 are generic and encompass species of formula II claimed in the instant application.
USPAT’620 does not teach specifically a method of treating Non-syndromic hearing loss/ autosomal recessive deafness due to SNPs in OTOF gene. However, Liu teaches using ADAR fusion protein and specific guide RNAs targeting specific SNPs in OTOF gene (see columns 337-338, Table 2).
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 USPAT’620 and Liu and designed AONs with optimum efficacy when using a gene editing system comprising an ADAR fusion protein. One with ordinary skills in the art, motivated in obtaining an efficient gene editing system using guide molecule targeting the SNPs in OTOF gene using and ADAR fusion protein as taught by Liu, could have modified the guide molecules in Table 2 (columns 337-338) and apply the rules for modifications adapted to ADAR proteins, as optimized by USPAT’620 according to the formula [Am]-X1-X2-X3-[Bn] and wherein X has the formula II, as taught by USPAT’620. One with ordinary skills in the art could have performed these modifications with a reasonable expectation of success and arrived at the claimed invention.
Claims 1-2, 4, 19, 124 and 145 are rejected on the ground of non-statutory double patenting as being unpatentable over claims 1-19, 21 and 23-28 of U.S. Patent No. 12,173,285 B2, in view of Liu (Liu, D.R. et al. US Patent No. 10,113,163 B2, dated October 30, 2018, with prior publication of US 2018/0073012 A1 on March 15, 2018).
Regarding claims 1-2, 4, 19, 124 and 145, claims 1-17 of USPAT’285 teaches all the limitations described in the claims 19, 124 and 145 for designing a guide RNA molecule according to according to the formula [Am]-X1-X2-X3-[Bn] and wherein X has the formula I (same as claim 19). Claims 18-19, 21 and 23-38, of USPAT’285 are drawn to method of editing using deamination of an adenosine in an mRNA, the method comprising contacting the oligonucleotide of claim 1 with a cell. Therefore the claims 1-19, 21 and 23-28 of USPAT’285 are generic and encompass species of formula I claimed in the instant application.
USPAT’285 does not teach specifically a method of treating Non-syndromic hearing loss/ autosomal recessive deafness due to SNPs in OTOF gene. However, Liu teaches using ADAR fusion protein and specific guide RNAs targeting specific SNPs in OTOF gene (see columns 337-338, Table 2).
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 USPAT’285 and Liu and designed AONs with optimum efficacy when using a gene editing system comprising an ADAR fusion protein. One with ordinary skills in the art, motivated in obtaining an efficient gene editing system using guide molecule targeting the SNPs in OTOF gene using and ADAR fusion protein as taught by Liu, could have modified the guide molecules in Table 2 (columns 337-338) and apply the rules for modifications adapted to ADAR proteins, as optimized by USPAT’285 according to the formula [Am]-X1-X2-X3-[Bn] and formula I, as taught by USPAT’285. One with ordinary skills in the art could have performed these modifications with a reasonable expectation of success and arrived at the claimed invention.
Claims 1-2, 4, 19, 124 and 145 are rejected on the ground of non-statutory double patenting as being unpatentable over claims 1-13 and 15-17 of U.S. Patent No. 11,479,575 B2, in view of Liu (Liu, D.R. et al. US Patent No. 10,113,163 B2, dated October 30, 2018, with prior publication of US 2018/0073012 A1 on March 15, 2018).
Regarding claims 1-2, 4, 19, 124 and 145, claims 1-13, and 15 of USPAT’575 teaches all the limitations described in the claims 19, 124 and 145 for designing a guide RNA molecule according to according to the formula [Am]-X1-X2-X3-[Bn] and wherein X has the formula IV (corresponding to formula IX in claim 19). Claims 16 and 17, of USPAT’575 are drawn to method of editing using deamination of an adenosine in an mRNA, the method comprising contacting the oligonucleotide of claim 1 with a cell. Therefore the claims 1-13, and 15-17 of USPAT’575 are generic and encompass species of formula IV claimed in the instant application.
USPAT’575 does not teach specifically a method of treating Non-syndromic hearing loss/ autosomal recessive deafness due to SNPs in OTOF gene. However, Liu teaches using ADAR fusion protein and specific guide RNAs targeting specific SNPs in OTOF gene (see columns 337-338, Table 2).
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 USPAT’575 and Liu and designed AONs with optimum efficacy when using a gene editing system comprising an ADAR fusion protein. One with ordinary skills in the art, motivated in obtaining an efficient gene editing system using guide molecule targeting the SNPs in OTOF gene using and ADAR fusion protein as taught by Liu, could have modified the guide molecules in Table 2 (columns 337-338) and apply the rules for modifications adapted to ADAR proteins, as optimized by USPAT’575 according to the formula [Am]-X1-X2-X3-[Bn] and formula IV, as taught by USPAT’575. One with ordinary skills in the art could have performed these modifications with a reasonable expectation of success and arrived at the claimed invention.
Claims 1-2, 4, 19, 124 and 145 are rejected on the ground of non-statutory double patenting as being unpatentable over claims 1-13 and 15-17 of U.S. Patent No. 12,152,050 B2, in view of Liu (Liu, D.R. et al. US Patent No. 10,113,163 B2, dated October 30, 2018, with prior publication of US 2018/0073012 A1 on March 15, 2018).
Regarding claims 1-2, 4, 19, 124 and 145, claims 1-13, and 15 of USPAT’050 teaches all the limitations described in the claims 19, 124 and 145 for designing a guide RNA molecule according to according to the formula [Am]-X1-X2-X3-[Bn] and wherein X has the formulas I-IV (corresponding to formulas VI to XI in claim 19). Claims 16 and 17, of USPAT’050 are drawn to method of editing using deamination of an adenosine in an mRNA, the method comprising contacting the oligonucleotide of claim 1 with a cell. Therefore the claims 1-13, 15 and 16-17 of USPAT’050 are generic and encompass species of formula I-IV claimed in the instant application.
USPAT’050 does not teach specifically a method of treating Non-syndromic hearing loss/ autosomal recessive deafness due to SNPs in OTOF gene. However, Liu teaches using ADAR fusion protein and specific guide RNAs targeting specific SNPs in OTOF gene (see columns 337-338, Table 2).
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 USPAT’050 and Liu and designed AONs with optimum efficacy when using a gene editing system comprising an ADAR fusion protein. One with ordinary skills in the art, motivated in obtaining an efficient gene editing system using guide molecule targeting the SNPs in OTOF gene using and ADAR fusion protein as taught by Liu, could have modified the guide molecules in Table 2 (columns 337-338) and apply the rules for modifications adapted to ADAR proteins, as optimized by USPAT’050 according to the formula [Am]-X1-X2-X3-[Bn] and formula I-IV, as taught by USPAT’050. One with ordinary skills in the art could have performed these modifications with a reasonable expectation of success and arrived at the claimed invention.
Claims 1, 4, 14, 16, 19, 124 and 145 provisionally rejected on the ground of non-statutory double patenting as being unpatentable over claims 1, 6, 8, 9, 10, 19-21, 46-49 , 52 and 61 of co-pending Application No. 18/290,062 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Regarding claims 1, 4, 14 and 16, co-pending app. 062’s claims 1, 46-49, 52
and 61 are drawn to an oligonucleotide comprising a guide molecule targeting a mRNA having a SNP in OTOF gene, wherein the SNPs are pathogenic mutations rs201326023, rs80356593 and rs80356592 in OTOF gene leading to amino acid substitutions R1939Q, R794H or Q829X in OTOF proteins. Claims 1, 46-49, 52 and 61 are drawn to method of editing a target polynucleotide comprising contacting the target polynucleotide with an oligonucleotide of claim 1, thereby editing the target mRNA that can be OTOF mRNA, and to a method of treating a disease associated with the SNP by administering the oligonucleotide of claim 1.
Regarding claims 19, 124 and 145, co-pending app.062’s claims 6, 8, 9, 10, 19
21 are drawn to an oligonucleotide that comprises the formula [Am]-X1-X2-X3-[Bn], with modifications claimed and encompassed in instant application’s claims 19, 124 and 145.
This is a provisional non-statutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 2, 4, 19, 124 and 145 are provisionally rejected on the ground of non-statutory double patenting as being unpatentable over claims 1-10, and 18-23 of co-pending Application No. 19/039,578 in view of Liu (Liu, D.R. et al. US Patent No. 10,113,163 B2, dated October 30, 2018, with prior publication of US 2018/0073012 A1 on March 15, 2018).
Regarding claims 1-2, 4, 19, 124 and 145, claims 1-10, and 18-23 of co-pending app. 578 teaches all the limitations described in the claims 19, 124 and 145 for designing a guide RNA molecule according to according to the formula [Am]-X1-X2-X3-[Bn]. claims 1-10 and 18-23 are drawn to an oligonucleotide specific of editing using ADAR-mediated deamination of an adenosine in an mRNA. Therefore the claims 1-10 and 18-23 of co-pending app. 578 are drawn to a subset of species described in instant application.
Co-pending app. 578 does not teach specifically an oligonucleotide specific for OTOF gene, nor a method of treating Non-syndromic hearing loss/ autosomal recessive deafness due to SNPs in OTOF gene. However, Liu teaches using ADAR fusion protein and specific guide RNAs targeting specific SNPs in OTOF gene (see columns 337-338, Table 2).
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 Co-pending app. 578 and Liu and designed AONs with optimum efficacy when using a gene editing system comprising an ADAR fusion protein. One with ordinary skills in the art, motivated in obtaining an efficient gene editing system using guide molecule targeting the SNPs in OTOF gene using and ADAR fusion protein as taught by Liu, could have modified the guide molecules in Table 2 (columns 337-338) and apply the rules for modifications adapted to ADAR proteins, as optimized by Co-pending app. 578 according to the formula [Am]-X1-X2-X3-[Bn], as taught by Co-pending App. 578. One with ordinary skills in the art could have performed these modifications with a reasonable expectation of success and arrived at the claimed invention.
This is a provisional non-statutory double patenting rejection.
Claims 1, 2, 4, 19, 124 and 145 are provisionally rejected on the ground of non-statutory double patenting as being unpatentable over claims 1-3, 6-7, 11, 14-15, 17-18, 20-28, 34-35, 41, 46 and 55 of co-pending Application No. 18/570,938 in view of Liu (Liu, D.R. et al. US Patent No. 10,113,163 B2, dated October 30, 2018, with prior publication of US 2018/0073012 A1 on March 15, 2018).
Regarding claims 1-2, 4, 19, 124 and 145, claims 1-3, 6-7, 11, 14-15, 17-18, 20-28, 34-35, 41 of co-pending app. 938 teaches all the limitations described in the claims 19, 124 and 145 for designing a guide RNA molecule according to according to the formula [Am]-X1-X2-X3-[Bn]. Claims 46 and 55 are drawn to a method of editing using ADAR-mediated deamination of an adenosine in an mRNA and a method of treating a disease associated with a SNP in a subject in need thereof. Therefore the claims 1-3, 6-7, 11, 14-15, 17-18, 20-28, 34-35, 41, 46 and 55 of co-pending app. 938 are drawn to a subset of oligonucleotides species described in instant application for the method of treating a subject in need thereof.
Co-pending app. 938 does not teach specifically an oligonucleotide specific for OTOF gene, nor a method of treating Non-syndromic hearing loss/ autosomal recessive deafness due to SNPs in OTOF gene. However, Liu teaches using ADAR fusion protein and specific guide RNAs targeting specific SNPs in OTOF gene (see columns 337-338, Table 2).
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 Co-pending app. 938 and Liu and designed AONs with optimum efficacy when using a gene editing system comprising an ADAR fusion protein. One with ordinary skills in the art, motivated in obtaining an efficient gene editing system using guide molecule targeting the SNPs in OTOF gene using and ADAR fusion protein as taught by Liu, could have modified the guide molecules in Table 2 (columns 337-338) and apply the rules for modifications adapted to ADAR proteins, as optimized by Co-pending app. 938 according to the formula [Am]-X1-X2-X3-[Bn], as taught by Co-pending App. 938. One with ordinary skills in the art could have performed these modifications with a reasonable expectation of success and arrived at the claimed invention.
This is a provisional non-statutory double patenting rejection.
Claims 1, 2, 4, 19, 124 and 145 are provisionally rejected on the ground of non-statutory double patenting as being unpatentable over claims 1-26 and 29 of co-pending Application No. 19/189,150 in view of Liu (Liu, D.R. et al. US Patent No. 10,113,163 B2, dated October 30, 2018, with prior publication of US 2018/0073012 A1 on March 15, 2018).
Regarding claims 1-2, 4, 19, 124 and 145, claims 1-26 of co-pending app. 150 teaches all the limitations described in the claims 19, 124 and 145 for designing a guide RNA molecule according to according to the formula [Am]-X1-X2-X3-[Bn]. Claim 29 is drawn to a method of editing using ADAR-mediated deamination of an adenosine in a target mRNA. Therefore the claims 1-26 and 29 of co-pending app. 150 are drawn to a subset of oligonucleotides species described in instant application for the method of treating a subject in need thereof.
Co-pending app. 150 does not teach specifically an oligonucleotide specific for OTOF gene, nor a method of treating Non-syndromic hearing loss/ autosomal recessive deafness due to SNPs in OTOF gene. However, Liu teaches using ADAR fusion protein and specific guide RNAs targeting specific SNPs in OTOF gene (see columns 337-338, Table 2).
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 Co-pending app. 150 and Liu and designed AONs with optimum efficacy when using a gene editing system comprising an ADAR fusion protein. One with ordinary skills in the art, motivated in obtaining an efficient gene editing system using guide molecule targeting the SNPs in OTOF gene using and ADAR fusion protein as taught by Liu, could have modified the guide molecules in Table 2 (columns 337-338) and apply the rules for modifications adapted to ADAR proteins, as optimized by Co-pending app. 150 according to the formula [Am]-X1-X2-X3-[Bn], as taught by Co-pending App. 150. One with ordinary skills in the art could have performed these modifications with a reasonable expectation of success and arrived at the claimed invention.
This is a provisional non-statutory double patenting rejection.
Claims 1, 2, 4, 19, 124 and 145 are provisionally rejected on the ground of non-statutory double patenting as being unpatentable over claims 60-81 of co-pending Application No. 19/296,642 in view of Liu (Liu, D.R. et al. US Patent No. 10,113,163 B2, dated October 30, 2018, with prior publication of US 2018/0073012 A1 on March 15, 2018).
Regarding claims 1-2, 4, 19, 124 and 145, claims 60-81 of co-pending app. 642 teaches the limitations described in the claims 19, 124 and 145 for designing a guide RNA molecule according to according to the formula [Am]-X1-X2-X3-[Bn] wherein X has the formulas I-IV (corresponding to formulas XII to XV of claim 19). Claim 80 of co-pending app. 642 is drawn to a method of editing using ADAR-mediated deamination of an adenosine in a target mRNA. Claim 81 of co-pending app. 642 is drawn to a method of treating a disorder in a subject in need thereof. Therefore the claims 60-81 of co-pending app. 642 are drawn to a subset of oligonucleotides species described in instant application for the method of treating a subject in need thereof.
Co-pending app. 642 does not teach specifically an oligonucleotide specific for OTOF gene, nor a method of treating Non-syndromic hearing loss/ autosomal recessive deafness due to SNPs in OTOF gene. However, Liu teaches using ADAR fusion protein and specific guide RNAs targeting specific SNPs in OTOF gene (see columns 337-338, Table 2).
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 Co-pending app. 642 and Liu and designed AONs with optimum efficacy when using a gene editing system comprising an ADAR fusion protein. One with ordinary skills in the art, motivated in obtaining an efficient gene editing system using guide molecule targeting the SNPs in OTOF gene using and ADAR fusion protein as taught by Liu, could have modified the guide molecules in Table 2 (columns 337-338) and apply the rules for modifications adapted to ADAR proteins, as optimized by Co-pending app. 642 according to the formula [Am]-X1-X2-X3-[Bn], as taught by Co-pending App. 642. One with ordinary skills in the art could have performed these modifications with a reasonable expectation of success and arrived at the claimed invention.
This is a provisional non-statutory double patenting rejection.
Additional Provisional Non Statutory Double Patenting rejections of claims 1, 2, 4, 19, 124 and 145 are as follow:
claims 1-4, 6, 9, 14, 18, 20-23, 30, 35-37, 41 and 50 of co-pending Application No. 18/570,918 in view of Liu (Liu, D.R. et al. US Patent No. 10,113,163 B2, dated October 30, 2018, with prior publication of US 2018/0073012 A1 on March 15, 2018).
Claims 1-7, 10, 13, 16, 53, 57-58, 60-61 and 73-75 of co-pending Application No. 18/927,268 in view of Liu (Liu, D.R. et al. US Patent No. 10,113,163 B2, dated October 30, 2018, with prior publication of US 2018/0073012 A1 on March 15, 2018).
Claims 1-20, 24-25 and 27 of co-pending Application No. 18/941,793 in view of Liu (Liu, D.R. et al. US Patent No. 10,113,163 B2, dated October 30, 2018, with prior publication of US 2018/0073012 A1 on March 15, 2018).
Conclusion
No claim is allowed.
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/A.D./Examiner, Art Unit 1636
/NANCY J LEITH/Primary Examiner, Art Unit 1636