DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
FINALITY
The finality of the Office Action filed 6 February 2026 has been withdrawn in favor of the new grounds of rejection below.
Application Status
This action is written in response to applicant’s correspondence received 31 March 2026. Claims 1-4, 6-29, 39-49, and 53-54 are currently pending. Claims 11-12, 16-17, 25-29, 39-49, and 53-54 are withdrawn from prosecution as being drawn to non-elected subject matter. Accordingly, claims 1-4, 6-10, 13-15, and 18-24 are examined herein. The restriction requirement mailed 11 June 2025 is still deemed proper. Applicant's elected Group I, SEQ ID NO: 267, 168, 225, 1, 58, 57, and a coronavirus S2M sequence without traverse in the reply filed 11 August 2025. For the purposes of examination, the species of SEQ ID NOs: 270-271 in claim 6 are rejoined.
Withdrawn Claim Rejections - 35 USC § 103
Any rejection or objection not reiterated herein has been overcome by argument.
Applicant’s arguments, see pg. 9-10, filed 31 March 2026, with respect to the rejection(s) of claim(s) 1-4, 6, 7, and 18-22 under 35 USC 103 have been fully considered and are persuasive. Applicant alleges that Yang teaches a T18 mutation in a Cas13b guide sequence and not a Cas13b direct repeat sequence (Remarks; pg. 9). This argument is found persuasive.
Therefore, the rejection of claims 1-4, 6-7, and 18-22 under 35 USC 103 as being unpatentable over Gootenburg in view of Yang has been withdrawn.
Because the newly recited rejections below are not necessitated by amendment, this action is NON-FINAL. Additionally, the amendment reciting “wherein each crRNA is at least 45 nucleotides in length”, filed 31 March 2026, has been entered for the purposes of examination.
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 nonobviousness.
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.
Claim(s) 1-4, 6-7, and 18-22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Gootenburg (PG Pub No. US 2020/0231975 A1) in view of Slaymaker ("High-resolution structure of Cas13b and biochemical characterization of RNA targeting and cleavage." Cell reports 26.13 (2019): 3741-3751).
Regarding claims 1 and 6, Gootenburg is directed towards a study concerned with non-naturally occurring or engineered RNA-targeting systems comprising a novel RNA-targeting CRISPR effector protein and at least one targeting nucleic acid component like a guide RNA (Abstract). Gootenburg teaches the use of a Cas13b guide RNA array that comprises different guide RNAs (i.e., a tandem array comprising at least two guide RNAs) that could be processed by Cas13b and knockdown their respective targets comparably to single guide controls ([0881]). Gootenburg teaches that the Cas13b guide RNAs comprise a direct repeat sequence fused or linked to a guide or spacer sequence ([0398]). Gootenburg teaches the use of a PspCas13b direct repeat sequence that has 100% identity to the claimed SEQ ID NOs: 270 and 272 except for a single T18G mutation (see SEQ ID NO: 270) or a single T18A mutation (see SEQ ID NO: 272) (pg. 238; see SEQ ID NO: 83 in previously attached sequence alignments). Gootenburg teaches that the direct repeat sequences of Cas13 proteins comprise a stem loop structure ([0029]). Gootenburg teaches that mutations may be introduced into the stem loop, whereby the cleavage activity of the effector protein is modulated ([0069]). Gootenburg teaches that the spacer sequence may be from 15-35 nucleotides in length (i.e., resulting in a total crRNA length of greater than 45 nucleotides when fused or linked to the PspCas13b direct repeat sequence) ([0400]).
Gootenburg does not teach or suggest that the direct repeat sequence comprises a T18 nucleotide mutation with respect to the DR sequence of PspCas13b (Claim 1). Gootenburg does not teach or suggest that each crRNA comprises a DR repeat sequence independently selected from SEQ ID NOs: 270 and SEQ ID NOs: 272 through the use of T18G and T18A mutations, respectively (Claim 6).
Slaymaker is drawn towards a study concerned with the study of Cas13b proteins, their high resolution structure, and the characterization of their RNA targeting and cleavage (pg. 3741). Slaymaker teaches the use of a PbuCas13b guide RNA that comprises a direct repeat sequence that further comprises a stem loop structure with a uracil at position 18 (i.e., termed “U(-18)”) with respect to the direct repeat sequence (pg. 3744; see Figure 2). Slaymaker teaches that mutating U (-18) to a guanine abolished general nuclease activity, but that other base mutations, including adenine and cytosine mutations, are tolerated such that the nuclease cleavage activity was maintained (pg. 3745; see Fig. S2P) (pg. 3745).
Thus, Slaymaker teaches that position 18 of a Cas13b direct repeat RNA sequence can be mutated and comprise either a uracil, an adenine, or a cytosine and that the resulting mutation still allows for the Cas13b to have cleavage activity.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have arrived at the requirements of the claimed T18G or T18A mutation in the claimed SEQ ID NOs: 270 and 272 because it would have merely amounted to a simple substitution of one known base pair for another at a position in a Cas13b direct repeat sequences that is tolerant to mutations. Because each of the two direct repeat sequences of Gootenburg and Slaymaker utilize Cas13b direct repeat sequences in a similar way, namely the cleavage of target nucleic acids by Cas13b proteins, then it would have been predictable to have mutated the direct repeat sequence of Gootenburg with a T18G or T18A mutation, arriving at a cytosine and uracil at position 18 in the transcribed RNA molecule, and maintained the PspCas13b’s cleavage activity.
Regarding claim 2, Gootenburg teaches the use of a Cas13b guide RNA array that comprises different guide RNAs (i.e., a tandem array comprising at least two guide RNAs) that could be processed by Cas13b and knockdown their respective targets comparably to single guide controls ([0881]).
Regarding claim 3, the obviousness of utilizing two different direct repeat sequences selected from the claimed SEQ ID NOs: 270 and 272 is discussed above as applied to claims 1 and 6.
Regarding claim 4, Gootenburg teaches that the crRNA comprises a stem loop (i.e., a loop region) that may comprise a mutation ([0069]).
Regarding claim 7, Gootenburg teaches that the direct repeat sequence may be 3’ from the guide sequence ([0398]).
Regarding claim 18, Gootenburg teaches that use of a vector comprising a tandem guide strategy (i.e., a composition comprising the tandem array comprising at least two crRNAs) that can increase the number of gRNAs by approximately 1.5 times in a single vector ([0122], [0423]).
Regarding claims 19-20, Gootenburg teaches the use of a vector that can comprise a Cas13 protein and one or more guide RNAs ([0445]).
Regarding claim 21, Gootenburg teaches the use of a Prevotella sp. Cas13 protein that has 100% sequence identity to the claimed SEQ ID NO: 1 that complexes with a guide RNA comprising a direct repeat sequence ([0137]; pg. 32; see SEQ ID NO: 84 in previously attached sequence alignment).
Regarding claim 22, Gootenburg teaches that the Cas13 protein may comprise a NLS or NES ([0422]).
Claim(s) 8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Gootenburg (PG Pub No. US 2020/0231975 A1) in view of Slaymaker ("High-resolution structure of Cas13b and biochemical characterization of RNA targeting and cleavage." Cell reports 26.13 (2019): 3741-3751) as applied to claims 1-4, 6-7, and 18-22 above, and further in view of Nguyen (Cell research 30.3 (18 February 2020): 189-190).
Regarding claim 8, Gootenburg in view of Slaymaker renders obvious claims 1-4, 6-7, and 18-22 as described above.
Gootenburg in view of Slaymaker does not teach or suggest that each guide sequence is independently substantially complementary to a Coronavirus genomic mRNA sequence (Claim 8).
Nguyen is drawn towards a study concerned with a potential treatment for SARS-CoV-2 and other RNA viruses that cause severe respiratory illness (pg. 189). Nguyen teaches the use of an AAV that comprises nucleotide sequences encoding a Cas13d protein and a tandem array of three Cas13 crRNAs, wherein each crRNA comprises different guide sequences (pg. 190; see Fig. 1E). Nguyen also teaches that the AAV comprises boxes (i.e., boxes that one of ordinary skill in the art would recognize as direct repeat sequences) located between the guide sequences (pg. 190; see Fig. 1E). Nguyen teaches that the CRISPR/Cas13 guide RNAs can be engineered such that the guide sequence contains spacer sequences that are complementary to SARS-CoV-2 RNA genomes (i.e., the guide sequences are complementary to SARS-CoV-2 mRNA) (pg. 189). Nguyen teaches that Cas13 guide RNA arrays can be designed and expressed within a target cell alongside the Cas13 protein in order to target SARS-CoV-2 RNA (pg. 190). Nguyen teaches that 10,333 different guide RNAs were designed to target 10 peptide-coding regions of the SARS-CoV-2 genome (pg. 189).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have arrived at the requirements of the claimed guide sequences that are independently complementary to a Coronavirus genomic mRNA sequence because it would have merely amounted to a simple substitution of one known Cas13 guide RNA sequence for another. Because Nguyen teaches the design of Cas13 guide RNA sequences that were utilized for a similar purpose as Gootenburg and Slaymaker, namely the targeting and editing of target RNA sequences with Cas13 proteins, then it would have been predictable to have utilized the guide RNA sequences of Nguyen in the tandem array of Gootenburg and Slaymaker in order to target and cleave SARS-CoV-2 mRNA. And because Nguyen teaches that SARS-CoV-2 mRNA causes severe respiratory illness, one would have been motived to do so in order to treat the illness.
Claim(s) 9-10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Gootenburg (PG Pub No. US 2020/0231975 A1) in view of Slaymaker ("High-resolution structure of Cas13b and biochemical characterization of RNA targeting and cleavage." Cell reports 26.13 (2019): 3741-3751) and Nguyen (Cell research 30.3 (18 February 2020): 189-190) as applied to claim 8 above, and further in view of Gumrukcu (PG Pub No: US 2021/0238232 A1, claiming priority to Provisional Application No. 62/985,597 “the ‘597 application”, filed 5 March 2020).
Regarding claims 9-10, Gootenburg in view of Slaymaker and Nguyen renders obvious claim 8 as described above.
Gootenburg in view of Slaymaker and Nguyen does not teach or suggest that each guide sequence is independently complementary to a Coronavirus leader sequence (Claim 9). Gootenburg in view of Slaymaker and Nguyen does not teach or suggest that each guide sequence is independently complementary to a sequence at least 80% homologous to the claimed SEQ ID NO: 168 (Claim 10).
Gumrukcu is drawn towards an invention concerned with methods of targeting viral infections and reducing/eliminating viral load (Abstract). Gumrukcu teaches that Gumrukcu teaches the use of a 5’-UTR leading sequence of COVID-19, also termed SARS, that comprises a sequence having 100% identity to the claimed SEQ ID NO: 168 ([0077]; see SEQ ID NO: 25 in previously attached sequence alignment; see [0069] of the ‘597 application).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have arrived at the requirements of the claimed guide sequences each being independently selected from claimed and elected SEQ ID NO: 168 because it would have merely amounted to a simple substitution of one known viral target sequence for another. Because Nguyen teaches the use of a viral SARS leading sequence, namely a sequence that could be targeted by a designed guide RNA as taught by Gootenburg, Slaymaker, and Nguyen in order to treat a respiratory disease, it would have been predictable to have substituted the guide RNA sequences of the tandem array such that they were each independently complementary to the claimed SEQ ID NO: 168 in order to target and treat diseases associated with SARS viral nucleic acids.
Claim(s) 13-14 is/are rejected under 35 U.S.C. 103 as being unpatentable over Gootenburg (PG Pub No. US 2020/0231975 A1) in view of Slaymaker ("High-resolution structure of Cas13b and biochemical characterization of RNA targeting and cleavage." Cell reports 26.13 (2019): 3741-3751) as applied to claims 1-4, 6-7, and 18-22 above, and further in view of Bawage (PG Pub No: WO 2019/204210 A1).
Regarding claim 14, Gootenburg in view of Slaymaker renders obvious claims 1-4, 6-7, and 18-22 as described above.
Gootenburg in view of Slaymaker does not teach or suggest that each guide sequence is complementary to an influenza virus PB1 sequence (Claims 13-14).
Bawage is drawn towards a study concerned with treating or inactivating viruses in a subject in need using an RNA-guided endonuclease and guide RNA (Abstract). Bawage teaches the use of a Cas13 that can complex with a guide RNA that has been designed in order to target a viral influezne PB1 sequence and treat a viral infection (pg. 3-4; see Figures 2A-2K).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have arrived at the requirements of the claimed guide sequences that are independently complementary to an influenza PB1 sequence because it would have merely amounted to a simple substitution of one known Cas13 guide RNA sequence for another. Because Bawage teaches the design of Cas13 guide RNA sequences that were utilized for a similar purpose as Gootenburg and Slaymaker, namely the targeting and editing of target viral genes with Cas13 proteins, then it would have been predictable to have utilized the guide RNA sequences of Bawage in the tandem array of Gootenburg and Slaymaker in order to target a viral influenza PB1 sequence. And because Bawage teaches that viral influenza PB1 sequences cause viral infections, one would have been motived to do so in order to treat the infection.
Claim(s) 15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Gootenburg (PG Pub No. US 2020/0231975 A1) in view of Slaymaker ("High-resolution structure of Cas13b and biochemical characterization of RNA targeting and cleavage." Cell reports 26.13 (2019): 3741-3751) and Bawage (PG Pub No: WO 2019/204210 A1) as applied to claims 13-14 above, and further in view of Gardner (PG Pub No: US 2013/0267429 A1).
Regarding claim 15, Gootenburg in view of Slaymaker and Bawage renders obvious claims 13-14 as described above.
Gootenburg in view of Slaymaker and Bawage does not teach or suggest that each guide sequence is independently substantially complementary to the claimed SEQ ID NO: 225 (Claim 15).
Gardner is drawn towards an invention concerned with sample target classification and detection methods utilizing oligonucleotide probes (Abstract). Gardner teaches that oligonucleotide probes can be utilized to target and detect flu RNA species ([0095]). Gardner teaches the use of an oligonucleotide probe that has 100% sequence identity to the claimed SEQ ID NO: 225 and can detect (i.e., target) an orthomyxoviridae flu species (pg. 39; see Table 1 and SEQ ID NO: 54405 in attached sequence alignment) (pg. 38-39; see Table 11).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have arrived at the requirements of the claimed guide sequences that are complementary to the claimed SEQ ID NO: 225 because it would have merely amounted to a simple substitution of one known Cas13 guide RNA target sequence for another. Because Gardner teaches the design of oligonucleotide probes that could be utilized for a similar purpose as Gootenburg, Slaymaker, and Bawage, namely the targeting of target viral influenza genes, then it would have been predictable to have utilized the target RNA sequence of Gardner in the tandem array of Gootenburg, Slaymaker, and Bawage in order to target and cleave the claimed viral influenza sequence.
Claim(s) 23 is/are rejected under 35 U.S.C. 103 as being unpatentable over Gootenburg (PG Pub No. US 2020/0231975 A1) in view of Slaymaker ("High-resolution structure of Cas13b and biochemical characterization of RNA targeting and cleavage." Cell reports 26.13 (2019): 3741-3751) as applied to claims 1-4, 6-7, and 18-22 above, and further in view of Bright (PG Pub No. US 2003/0104479 A1).
Regarding claim 23, Gootenburg in view of Slaymaker renders obvious claims 1-4, 6-7, and 18-22 as described above. Gootenburg further teaches that the Cas13 protein may comprise a functional NES domain ([0721]-[0722]).
Gootenburg in view of Slaymaker does not teach or suggest that the NES comprises a sequence at least 80% identical to SEQ ID NO: 58 (Claim 23).
Bright is drawn towards an invention concerned with novel recombinant fusion proteins (Abstract). Bright teaches that NES localization domains may be fused to a recombinant fusion protein of interest ([0048]). Bright teaches that an HIV Rev NES having 100% sequence identity to the claimed SEQ ID NO: 58 was a well-known NES in the art ([0020]; see FIG. 4 and SEQ ID NO: 156 in attached sequence alignment).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have arrived at the requirements of the claimed NES comprising at least 80% identity to the claimed SEQ ID NO: 58 because it would have merely amounted to a simple substitution of one known NES for another. Because Bright teaches the use of NES sequences for a similar purpose as Gootenburg, Slaymaker, and Bawage, namely the fusion of the NES sequences to a heterologous protein, then it would have been predictable to have utilized the NES of Bright in the Cas protein of Gootenburg, Slaymaker, and Bawage in order to target and cleave nucleic acids of interest.
Claim(s) 24 is/are rejected under 35 U.S.C. 103 as being unpatentable over Gootenburg (PG Pub No. US 2020/0231975 A1) in view of Slaymaker ("High-resolution structure of Cas13b and biochemical characterization of RNA targeting and cleavage." Cell reports 26.13 (2019): 3741-3751) as applied to claims 1-4, 6-7, and 18-22 above, and further in view of Umezawa (PG Pub No: US 2007/0178464 A1).
Regarding claim 24, Gootenburg in view of Slaymaker renders obvious claims 1-4, 6-7, and 18-22 as described above. Gootenburg further teaches that the Cas13 protein may comprise a functional NLS domain ([0721]-[0722]).
Gootenburg in view of Slaymaker does not teach or suggest that the NLS comprises a sequence at least 80% identical to SEQ ID NO: 54 (Claim 24).
Umezawa is drawn towards an invention concerned with detecting protein nuclear transport (Abstract). Umezawa teaches the use of an NLS having 100% identity to the claimed SEQ ID NO: 54 that could be fused to a recombinant protein ([0100], [0117]; see SEQ ID NO: 1 in attached sequence alignment).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have arrived at the requirements of the claimed NLS comprising at least 80% identity to the claimed SEQ ID NO: 54 because it would have merely amounted to a simple substitution of one known NLS for another. Because Umezawa teaches the use of NLS sequences for a similar purpose as Gootenburg, Slaymaker, and Bawage, namely the fusion of the NLS sequences to a heterologous protein, then it would have been predictable to have utilized the NLS of Umezawa in the Cas protein of Gootenburg, Slaymaker, and Bawage in order to target and cleave nucleic acids of interest.
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 1-4, 6-7, 18-22, and 24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 77, 82, 84-85, 87-90, and 92 of copending Application No. 17/628,913 (reference application) in view of Gootenburg (PG Pub No. US 2020/0231975 A1) and Slaymaker ("High-resolution structure of Cas13b and biochemical characterization of RNA targeting and cleavage." Cell reports 26.13 (2019): 3741-3751).
Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims anticipate the instantly pending claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding claim 1, copending claim 77 claims a CRISPR RNA (crRNA) comprising a guide sequence, wherein the guide sequence is substantially complementary to an expanded RNA repeat. Copending claim 84 claims a tandem array comprising at least two of the claimed crRNAs. Copending claim 82 claims that the crRNA further comprises a direct repeat (DR) sequence.
The copending claims do not teach or suggest that the direct repeat sequence comprises a T17 or T18 mutation with respect to the direct repeat sequence of PspCas13b (Claim 1).
However, the applicable teachings of Gootenburg and Slaymaker, and the obviousness rationale utilized to arrive at instant claims 1 and 6 are discussed above as applied to claims 1 and 6.
Regarding claim 3, copending claim 85 claims identical claim limitations.
Regarding claim 7, copending claim 82 claims identical claim limitations.
Regarding claims 2, 4 and 6, the applicable teachings of Gootenburg and Slaymaker, and the obviousness rationales utilized to arrive at instant claims 2, 4, and 6, are described above.
Regarding claim 18, the applicable teachings of Gootenburg and Slaymaker, and the obviousness rationales utilized to arrive at instant claim 18 is described above.
Regarding claims 19-22, copending claims 87-90 claim identical claim limitations.
Regarding claim 24, copending claim 92 claims identical claim limitations.
Claim 8 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 77, 82, 84-85, 87-90, and 92 of copending Application No. 17/628,913 (reference application) in view of Gootenburg (PG Pub No. US 2020/0231975 A1) and Slaymaker ("High-resolution structure of Cas13b and biochemical characterization of RNA targeting and cleavage." Cell reports 26.13 (2019): 3741-3751) as applied to claims 1-4, 6-7, 18-22, and 24 above, further in view of Nguyen (Cell research 30.3 (18 February 2020): 189-190).
Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims anticipate the instantly pending claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding claim 8, the copending claims in view of Gootenburg and Slaymaker renders obvious claims 1-4, 6-7, 18-22, and 24 as described above.
The copending claims in view of Gootenburg and Slaymaker does not teach or suggest that each guide sequence is independently substantially complementary to a Coronavirus genomic mRNA sequence (Claim 8).
However, the applicable teachings of Nguyen and the applicable rationale utilized to render claim 8 obvious is discussed above in the 35 USC 103 rejection of claim 8.
Claim(s) 9-10 is/are rejected under 35 U.S.C. 103 as being unpatentable over claims 77, 82, 84-85, 87-90, and 92 of copending Application No. 17/628,913 (reference application) in view of Gootenburg (PG Pub No. US 2020/0231975 A1), Slaymaker ("High-resolution structure of Cas13b and biochemical characterization of RNA targeting and cleavage." Cell reports 26.13 (2019): 3741-3751), and Nguyen (Cell research 30.3 (18 February 2020): 189-190) as applied to claim 8 above, and further in view of Gumrukcu (PG Pub No: US 2021/0238232 A1, effectively filed 5 September 2019).
Regarding claims 9-10, the copending claims in view of Gootenburg, Slaymaker, and Nguyen renders obvious claim 8 as described above.
The copending claims in view of Gootenburg, Slaymaker, and Nguyen does not teach or suggest that each guide sequence is independently complementary to a Coronavirus leader sequence (Claim 9). The copending claims in view of Gootenburg, Slaymaker, and Nguyen does not teach or suggest that each guide sequence is independently complementary to a sequence at least 80% homologous to the claimed SEQ ID NO: 168 (Claim 10).
However, the applicable teachings of Gumrukcu and the applicable rationale utilized to render claims 9-10 obvious is discussed above in the 35 USC 103 rejection of claims 9-10.
Claim(s) 13-14 is/are rejected under 35 U.S.C. 103 as being unpatentable over claims 77, 82, 84-85, 87-90, and 92 of copending Application No. 17/628,913 (reference application) in view of Gootenburg (PG Pub No. US 2020/0231975 A1) and Slaymaker ("High-resolution structure of Cas13b and biochemical characterization of RNA targeting and cleavage." Cell reports 26.13 (2019): 3741-3751) as applied to claims 1-4, 6-7, 18-22, and 24 above, and further in view of Bawage (PG Pub No: WO 2019/204210 A1).
Regarding claim 14, the copending claims in view of Gootenburg and Slaymaker renders obvious claims 1-4, 6-7, 18-22, and 24 as described above.
The copending claims in view of Gootenburg and Slaymaker does not teach or suggest that each guide sequence is complementary to an influenza virus PB1 sequence (Claim 14).
However, the applicable teachings of Bawage and the applicable rationale utilized to render claims 13-14 obvious is discussed above in the 35 USC 103 rejection of claims 13-14.
Claim(s) 15 is/are rejected under 35 U.S.C. 103 as being unpatentable over claims 77, 82, 84-85, 87-90, and 92 of copending Application No. 17/628,913 (reference application) in view of Gootenburg (PG Pub No. US 2020/0231975 A1), Slaymaker ("High-resolution structure of Cas13b and biochemical characterization of RNA targeting and cleavage." Cell reports 26.13 (2019): 3741-3751), and Bawage (PG Pub No: WO 2019/204210 A1) as applied to claims 13-14 above, and further in view of Gardner (PG Pub No: US 2013/0267429 A1).
Regarding claim 15, the copending claims in view of Gootenburg, Slaymaker, and Bawage renders obvious claims 13-14 as described above.
The copending claims in view of Gootenburg, Slaymaker, and Bawage does not teach or suggest that each guide sequence is independently substantially complementary to the claimed SEQ ID NO: 225 (Claim 15).
However, the applicable teachings of Gardner and the applicable rationale utilized to render claim 15 obvious is discussed above in the 35 USC rejection of claim 15.
Claim(s) 23 is/are rejected under 35 U.S.C. 103 as being unpatentable over claims 77, 82, 84-85, 87-90, and 92 of copending Application No. 17/628,913 (reference application) in view of Gootenburg (PG Pub No. US 2020/0231975 A1) and Slaymaker ("High-resolution structure of Cas13b and biochemical characterization of RNA targeting and cleavage." Cell reports 26.13 (2019): 3741-3751) as applied to claims 1-4, 6-7, 18-22, and 24 above, and further in view of Bright (PG Pub No. US 2003/0104479 A1).
Regarding claim 23, the copending claims in view of Gootenburg and Slaymaker renders obvious claims 1-4, 6-7, 18-22, and 24 as described above.
The copending claims in view of Gootenburg and Slaymaker does not teach or suggest that the NES comprises a sequence at least 80% identical to SEQ ID NO: 58 (Claim 23).
However, the applicable teachings of Bright and the applicable rationale utilized to render claim 23 obvious is discussed above in the 35 USC 103 rejection of claim 23.
Claims 1-4, 6-10, 13-14, 18-22, and 24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 6, 11-13, and 15-16 of copending Application No. 17/907,121 (reference application) in view of Gootenburg (PG Pub No. US 2020/0231975 A1) and Slaymaker ("High-resolution structure of Cas13b and biochemical characterization of RNA targeting and cleavage." Cell reports 26.13 (2019): 3741-3751).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding claim 1, copending claim 1 is drawn towards a method for treating a viral infection, the method comprising administering to the subject: (a) CRISPR RNA (crRNA) comprising guide sequence substantially complementary to a viral RNA sequence and (b) a Cas protein or nucleic acid encoding the Cas protein, wherein the Cas protein comprises a nuclear export signal (NES) comprising a sequence at least 80% identical to SEQ ID NOs: 58-59.
Copending claim 1 does not claim the use of a tandem array comprising at least two crRNAs, wherein each crRNA comprises a guide sequence and a DR sequence (Claim 1). The copending claims do not teach or suggest that the direct repeat sequence comprises a T17 or T18 mutation with respect to the direct repeat sequence of PspCas13b (Claim 1).
However, the applicable teachings and rationale of Gootenburg and Slaymaker that rendered claim 1 obvious over claims 77, 82, 84-85, 87-90, and 92 of copending Application No. 17/628,913 is discussed above.
Regarding claims 2, 4 and 6, the applicable teachings and rationale of Gootenburg and Slaymaker that rendered claims 2, 4, and 6, obvious over claims 77, 82, 84-85, 87-90, and 92 of copending Application No. 17/628,913 is discussed above.
Regarding claim 3, the applicable teachings and rationale of Gootenburg and Slaymaker that rendered claim 3 obvious in the 35 USC 103 rejection of claim 3 is discussed above.
Regarding claim 7, the applicable teachings and rationale of Gootenburg and Slaymaker that rendered claim 7 obvious in the 35 USC 103 rejection of claim 3 is discussed above.
Regarding claim 18, the applicable teachings and rationale of Gootenburg and Slaymaker that rendered claim 18, obvious over claims 77, 82, 84-85, 87-90, and 92 of copending Application No. 17/628,913 is discussed above.
Regarding claims 8-10, copending claims 11-13 claim identical claim limitations.
Regarding claims 13-14, copending claims 15-16 claim ide4ntical claim limitations.
Regarding claim 18, the applicable teachings and rationale of Gootenburg and Slaymaker that rendered claim 18, obvious over claims 77, 82, 84-85, 87-90, and 92 of copending Application No. 17/628,913 is discussed above.
Regarding claims 19-20, copending claims 1-2 claim the use of a Cas13 protein.
Regarding claim 20, copending claim 2 claims identical claim limitations.
Regarding claim 21, copending claim 3 claims identical claim limitations.
Regarding claims 22 and 24, copending claim 6 claims identical claim limitations.
Claim(s) 15 is/are rejected under 35 U.S.C. 103 as being unpatentable over claims 1-3, 6, 11-13, and 15-16 of copending Application No. 17/907,121 (reference application) in view of Gootenburg (PG Pub No. US 2020/0231975 A1) in view of Slaymaker ("High-resolution structure of Cas13b and biochemical characterization of RNA targeting and cleavage." Cell reports 26.13 (2019): 3741-3751) as applied to claims 1-4, 6-10, 13-14, 18-22, and 24 above, and further in view of Gardner (PG Pub No: US 2013/0267429 A1).
Regarding claim 15, the copending claims in view of Gootenburg and Slaymaker renders obvious claims 1-4, 6-10, 13-14, 18-22, and 24 as described above.
The copending claims in view of Gootenburg and Slaymaker does not teach or suggest that each guide sequence is independently substantially complementary to the claimed SEQ ID NO: 225 (Claim 15).
However, the applicable teachings of Gardner and the applicable rationale utilized to render claim 15 obvious is discussed above in the 35 USC 103 rejection of claim 15.
Claim(s) 23 is/are rejected under 35 U.S.C. 103 as being unpatentable over claims 1-3, 6, 11-13, and 15-16 of copending Application No. 17/907,121 (reference application) in view of Gootenburg (PG Pub No. US 2020/0231975 A1) in view of Slaymaker ("High-resolution structure of Cas13b and biochemical characterization of RNA targeting and cleavage." Cell reports 26.13 (2019): 3741-3751) as applied to claims 1-4, 6-10, 13-14, 18-22, and 24 above, and further in view of Bright (PG Pub No. US 2003/0104479 A1).
Regarding claim 23, the copending claims in view of Gootenburg and Slaymaker renders obvious claims 1-4, 6-10, 13-14, 18-22, and 24 as described above.
The copending claims in view of Gootenburg and Slaymaker does not teach or suggest that the NES comprises a sequence at least 80% identical to SEQ ID NO: 58 (Claim 23).
However, the applicable teachings of Bright and the applicable rationale utilized to render claim 23 obvious is discussed above in the 35 USC rejection of claim 23.
Response to Arguments
Insofar as Applicant’s arguments are applicable to the newly recited rejections of the claimed under 35 USC 103, the newly cited Slaymaker reference explicitly discloses that Cas13b direct repeat sequences can be mutated at position 18 of the direct repeat sequence, that the nucleotide at position 18 may be a uracil, a cytosine, or an adenine, and that the mutation of the nucleotide from a uracil to a cytosine did not abolish cleavage activity of the Cas13b protein.
Thus, Slaymaker provides evidence that the prior art had already mutated Cas13b DR sequences at the claimed nucleotide position and that the mutations present in the claimed SEQ ID NOs: 270 and 272 would have been expected to not completely abolish editing activity of the Cas13b protein.
Conclusion
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/KYLE T REGA/Examiner, Art Unit 1636
/NEIL P HAMMELL/Supervisory Patent Examiner, Art Unit 1636
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