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 .
Status
Claims 1, 4, 5, 7- 10, 12, 15, 16, 19, 20, 22, 23, 25- 27, 29, 31, 34, 35, 37- 40, 42, 44, 46, 47, 49- 56, and 58- 64 are pending.
Claims 1, 4, 5, 7- 10, 12, 15, 16, 19, 20, 22, 23, 25- 27, 29, 31, 34, 35, 37- 40, 42, 44, 46, 47, 49- 56, and 58- 64 are subject to restriction requirement/election of species.
Claims 1, 5, 7- 10, 12, 16, 20, 22, 23, 25- 27, 29, 31, 35, 37- 40, 42, 44, 46, 47, 49- 52, 54- 56, 58- 61, and 64 are examined on the merits.
Claims 4, 15, 19, 34, 39, 46, 53, 62, and 63 are withdrawn.
Claims 1, 5, 7- 10, 12, 16, 20, 22, 23, 25- 27, 29, 31, 35, 37- 40, 42, 44, 46, 47, 49- 52, 54- 56, 58- 61, and 64 are rejected.
No Claims are allowed.
The specifications are objected.
Election/Restrictions
Applicant’s election without traverse of:
Invention: Group I,
single crRNA sequence SEQ ID NO: 24,
a single tracrRNA sequence, SEQ ID NO: 126,
a single anti-tracrRNA sequence, SEQ ID NO: 27,
the first section of the tracrRNA, SEQ ID NO: 10,
the second section of the tracrRNA, SEQ ID NO: 12,
the second section of the tracrRNA, SEQ ID NO: 13,
the fourth section of the tracrRNA, a sequence of UUU,
the RNA scaffold, NGS17;
in the reply filed on April 24, 2026 is acknowledged.
Claims 4, 15, 19, 34, 39, 46, 53, 62 and 63 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention or species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on April 24, 2026.
Claims 4, 15, 19, 34, 39, 46, and 53 are withdrawn for the following reasons:
Claim 4 is directed toward crRNA repeat sequence portion SEQ ID No 23. However, applicant elected crRNA repeat sequence portion SEQ ID No 24.
Claim 15 is directed toward tracrRNA portion SEQ ID No 5. However, applicant elected tracrRNA portion SEQ ID No 126.
Claim 19 is directed toward tracrRNA anti-repeat sequence portion SEQ ID No 26. However, applicant elected tracrRNA anti-repeat sequence portion SEQ ID No 27.
Claim 34 is directed toward crRNA repeat sequence portion SEQ ID No 23. However, applicant elected crRNA repeat sequence portion SEQ ID No 24.
Claim 39 is directed toward tracrRNA portion SEQ ID No 5. However, applicant elected tracrRNA portion SEQ ID No 126.
Claim 46 is directed toward tracrRNA anti-repeat sequence portion SEQ ID No 5. However, applicant elected tracrRNA anti-repeat sequence portion SEQ ID No 27.
Claim 53 is directed toward RNA scaffold portion SEQ ID No 4, 5, 16-21, 29-31, 74- 126, 132-137, and 148-167. However, applicant elected RNA scaffold portion SEQ ID No 24.
Priority
Priority claim to US 63/109,835 via PCT/US2021/057814 is acknowledged. Claims 1, 4, 5, 7- 10, 12, 15, 16, 19, 20, 22, 23, 25- 27, 29, 31, 34, 35, 37- 40, 42, 44, 46, 47, 49- 56, and 58- 64 of the claim set filed April 24, 2026 are acknowledged the benefit of the effective filing date November 4, 2020.
Specification
The use of the term “OMNI-50,” which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears 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
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 1, 5, 7- 10, 12, 16, 20, 22, 23, 25- 27, 29, 31, 35, 37- 40, 42, 44, 46, 47, 49- 52, 54- 56, 58- 61, and 64 are 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.
Those claims included in the statement of rejection but not otherwise discussed are rejected for depending from a rejected claim but failing to remedy the indefiniteness therein.
The term “mature” in claims 1, 12, 29, and 38 is a relative term which renders the claim indefinite. The term “mature” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The term “mature” renders the “sequence identity to an… OMNI-50 crRNA repeat sequence encoded by Ezakiella peruensis strain M6.X2” indefinite(claims 1 and 29). The term “mature” renders the “sequence identity to an… OMNI-50 tracrRNA sequence encoded by Ezakiella peruensis strain M6.X2” indefinite (claims 12 and 38).
Claims 1, 10, 12, 27, 29, 38, 58, and 64 contain the trademark/trade name “OMNI-50.” Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe sequences and their expression products based on Ezakiella peruensis strain M6.X2 as described in the instant specifications paragraph [00188] and Tables 1- 9 and, accordingly, the identification/description is indefinite.
Claim 1 recites “wherein the tracrRNA sequence is encoded by a tracrRNA portion of the RNA molecule or a tracrRNA portion of a second RNA molecule” in lines 9, 10. The tracrRNA sequence is not “encoded” by a tracrRNA portion of an RNA molecule. The tracrRNA sequence would be encoded by a DNA molecule. Therefore the claim is indefinite.
Similarly, Claim 12 recites “wherein the crRNA repeat sequence portion and the guide sequence portion are encoded by the RNA molecule or a second RNA molecule” in lines 9, 10. The crRNA sequence is not “encoded” by a crRNA portion of an RNA molecule. The crRNA sequence would be encoded by a DNA molecule. Therefore the claim is indefinite.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 5, 7- 10, 12, 16, 20, 22, 23, 25- 27, 29, 31, 35, 37- 40, 42, 44, 46, 47, 49- 52, 54- 56, 58- 61, and 64 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 recites “A composition comprising a non-naturally occurring RNA molecule, the RNA molecule comprising a crRNA repeat sequence portion and a guide sequence portion,
wherein the crRNA repeat sequence portion has at least 60-70%, 71-80%, 81-90%, 91-95%, or 96-99% sequence identity to a mature OMNI-50 crRNA repeat sequence encoded by Ezakiella peruensis strain M6.X2 and is less than 17 nucleotides in length;
wherein the RNA molecule forms a complex with and targets an OMNI-50 nuclease to a DNA target site in the presence of a tracrRNA sequence; and
wherein the tracrRNA sequence is encoded by a tracrRNA portion of the RNA molecule or a tracrRNA portion of a second RNA molecule.”
Applicant has not provided sufficient written description to show they were in possession of the genus “crRNA repeat sequence portion has at least 60-70%, 71-80%, 81-90%, 91-95%, or 96-99% sequence identity to a mature OMNI-50 crRNA repeat sequence encoded by Ezakiella peruensis strain M6.X2 and is less than 17 nucleotides in length.”
The instant claim as a whole essentially claims a non-natural CRISPR/Cas complex. The claim’s four elements comprise 1) a generic gRNA (crRNA and gRNA); 2) further limitation of the crRNA portion to “60-70%, 71-80%, 81-90%, 91-95%, or 96-99% sequence identity to a mature OMNI-50 crRNA repeat sequence encoded by Ezakiella peruensis strain M6.X2 and is less than 17 nucleotides in length”; 3) CRISPR/Cas complex formation (including OMNI-50 nuclease, generic tracrRNA, and generic target DNA); and 4) further generic limitation of tracrRNA. Claim elements 1 and 4 are well known in the art and do not require further comment in describing the claim as a whole. Claim element 2 further limits the crRNA of the first element. This second claim element limits the crRNA sequence in terms of a commercial/proprietary CRISPR nuclease (OMNI-50) in which it purportedly interacts, and further limits the crRNA’s sequence to a “mature” derivative from an “immature sequence” from a bacteria species (Ezakiella peruensis) from which its sequence is derived. Furthermore, the second claim element allows for up to 60% deviation from the “mature” sequence but limits the crRNA to 17 nucleotides. The third claim element provides for the formation of the remaining components of the CRISPR/Cas complex; in particular the proprietary CRISPR OMNI-50 nuclease, generic target DNA and generic tracrRNA.
Regarding claim elements 1, 3, and 4, the specification provides sufficient written description. The “Field of the Invention” section of the specification, immediately followed by the first two sentences of the “Background of the Invention” states the scope of the claim “The present invention is directed to, inter alia, composition and methods for genome editing. The Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) systems of bacterial and archaeal adaptive immunity show extreme diversity of protein composition and genomic loci architecture. The CRISPR systems have become important tools for research and genome engineering.” Furthermore, the specification sufficiently describes the generic elements of the claim that are well known in the art: [00120, 00121] describes DNA target sequences; [00122] describes gRNA sequences; [00125] describes non-naturally occurring; [00129] describes nucleases; [00132-00136] describe the scaffolding dynamics of the CRISPR/Cas complex, including tracrRNA, crRNA, protein binding sequence; [00138] describes options for sgRNAs versus combination gRNAs with tracrRNAs. Regarding the CRISPR OMNI-50 nuclease, the specification provides sufficient written description. The specification defines it with SEQ ID No 1 and further allows for up to 95% variance “OMNI-50 CRISPR nuclease has at least 95% identity to the amino acid sequence of SEQ ID NO: 1” [0079]. The specification further identifies OMNI-50’s origin is Ezakiella peruensis strain M6.X2 (Table 1, page 46).
However, regarding the genus “crRNA repeat sequence portion has at least 60-70%, 71-80%, 81-90%, 91-95%, or 96-99% sequence identity to a mature OMNI-50 crRNA repeat sequence encoded by Ezakiella peruensis strain M6.X2 and is less than 17 nucleotides in length” the specification has not provided sufficient written description to show the applicant was in possession of the invention.
Table 1 identifies Ezakiella peruensis strain M6.X2 as the source of OMNI-50 nuclease, the crRNAs, and the tracrRNAs. Tables 3- 9 further identifies four crRNAs, SEQ ID No 8, 23- 25 as well as scaffold RNAs comprising these crRNA sequences.
The specification provides sufficient written description that the crRNA repeat sequence interacts with OMNI-50 nuclease in Figs. 5A-E “U2OS cells were electroporated with RNP of OMNI-50 with the indicated sgRNAs [comprising crRNA repeat sequence] and activity was determined.”
However, the “immature sequence” from which the crRNA is derived is not identified, but instead, only hinted at by the specification disclosure “OMNI-50 sequences, such as the OMNI-50 CRISPR repeat (crRNA) sequence, OMNI-50 transactivating crRNA (tracrRNA) sequence, and OMNI-50 nuclease polypeptide sequence, were predicted from Ezakiella peruensis strain M6.X2” [00188]. Furthermore, in addition to failing to identify the immature crRNA sequence, the specification fails to describe the specific modifications of immature crRNA that lead to specific mature crRNA repeat sequences. Furthermore, Figs. 1 and 2, and Tables 3 and 4 of the specification describe “trimming” of crRNA and “different lengths” of crRNA. However, it is unclear if these are part of the maturation process. Furthermore, beyond the previously four mentioned crRNAs, the specification does not identify nor make use of any variant crRNA, much less a crRNA repeat sequence with variance up to 60% identity to ANY potential mature crRNA sequence. Most importantly, the specification fails to clearly identify a single “mature OMNI-50 crRNA repeat sequence.” As stated previously, the specification mentions several crRNA sequences, but it does not describe these sequences as “mature.” Therefore, it is unclear whether the crRNA repeats sequences described are mature or immature sequences.
Whereas the specifications sufficiently described the aforementioned four crRNA repeat sequences, function, properties, and mode of manufacture, One skilled in the art would not recognize that the applicant was in possession of the claimed invention as a whole at the time of filing for the following reasons.
The applicant has failed to reduce to practice the invention as claimed, in regards to the genus “mature OMNI-50 crRNA repeat sequence.” The applicant provides experimental examples of only a fraction of the possible embodiments. Similarly, the drawings describe only these same four embodiments of crRNA repeat sequences. The genetic origin leading to the large number and variability of immature crRNA sequences is exemplified by Wakefield “short crRNAs, each harboring a unique invader-derived spacer sequence”(page 3202, 2nd column, middle) (Wakefield et al. FEBS Lett. 2015 Oct 7;589(20 Pt B):3197-204.). This fraction fails to represent the genus of crRNA and therefore a person having ordinary skill in the art (PHOSITA) would not accept four embodiments as exemplary of the genus. Furthermore, the crRNA repeat sequence is limited by its antisense (antirepeat) partner, as described by Doudna “Cas9 makes extensive interactions with the sgRNA. Specifically, it makes many direct contacts with the repeat–antirepeat duplex and stem loop 1,” (page 515, top) (Doudna et al. Annu Rev Biophys. 2017 May 22;46:505-529.). Therefore, the acceptable percent variance of the mature crRNA repeat sequence is restricted by the necessary sequence constraint of its requirements to pair with an antirepeat partner.
Similarly, the same rejection and analysis applies to the “mature tracrRNA sequence” of claim 12, and the “mature crRNA repeat sequence” of claim 29.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 5, 7- 10, 12, 16, 20, 22, 23, 25- 27, 29, 31, 35, 37- 40, 42, 44, 46, 47, 49- 52, 54- 56, 58- 61, and 64 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Baram2019 (Baram. WO 2020223514 A2, effectively filed April 30, 2019) .
The applied reference has a common applicant with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
Baram2019 teaches “a non-naturally occurring composition comprising a CRISPR associated system comprising:
a) one or more RNA molecules comprising a guide sequence portion linked to a direct repeat sequence, wherein the guide sequence is capable of hybridizing with a target sequence, or one or more nucleotide sequences encoding the one or more RNA molecules; and
b) a CRISPR nuclease comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 3 or a nucleic acid molecule comprising a sequence encoding the CRJSPR nuclease; and
wherein the one or more RNA molecules hybridize to the target sequence, wherein the target sequence is 3' of a Protospacer Adjacent Motif (PAM), and the one or more RNA molecules form a complex with the RNA-guided nuclease.” [0012].
Baram2019 further teaches the Ezakiella peruensis strain M6.X2 is the source organism for the OMIN-50 nuclease (SEQ ID No 3 above) (Table 1) and the crRNA:tracrRNA (Table 2) and further provides SEQ ID No for each. The crRNA repeat sequence listed in Table 2 is 9 nucleotides in length. Baram2019 further teaches the embodiment “the nuclease-binding RNA nucleotide sequence is on a first RNA molecule and the DNA-targeting RNA nucleotide sequence is on a single guide RNA molecule” [0050]. Baram2019 teaches “For the OMNI-50 nuclease, the sgRNA was predicted by detection of the CRISPR repeat array sequence (crRNA) and a trans-activating crRNA (tracrRNA) in the bacterial genome in which the nuclease was identified.” [00233]. Furthermore, Basam2019 teaches cellular application of the invention, “OMNI-50 was also assayed for its ability to promote editing on specific genomic locations in human cells.” [00239].
Therefore, Baram2019 teaches all of the elements of claims 1, 5, 7- 10, 12, 16, 20, 22, 23, 25- 27, 29, 31, 35, 37- 40, 42, 44, 46, 47, 49- 52, 54- 56, 58- 61, and 64.
Therefore, Baram2019 anticipates claims 1, 5, 7- 10, 12, 16, 20, 22, 23, 25- 27, 29, 31, 35, 37- 40, 42, 44, 46, 47, 49- 52, 54- 56, 58- 61, and 64.
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, 5, 7, 8, 9, and 10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 6, 7, and 9 of U.S. Patent No. US 11,666,641 B2. Claims 12, 16, 20, 22, 23, and 25- 27 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 6, 8, and 9 of U.S. Patent No. US 11,666,641 B2. Claims 29, 31, 35, 37, 38, 40, 42, 44, 47, 49- 52, 54- 56, 58- 61, and 64 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 6, and 9 of U.S. Patent No. US 11,666,641 B2. Although the claims at issue are not identical, they are not patentably distinct from each other because the scope of the recited claims of the patent anticipates instant claims.
The instant claim 1 recites “A composition comprising a non-naturally occurring RNA molecule…” The patent similarly claims “A non-naturally occurring composition, (claim 1) and a CRISPR RNA (crRNA) molecule and a transactivating CRISPR RNA (tracrRNA) molecule, wherein the crRNA molecule, tracrRNA molecule, and the CRISPR nuclease do not naturally occur together (claim 2).”
The instant claim 1 continues “the RNA molecule comprising a crRNA repeat sequence portion and a guide sequence portion…” The patent similarly claims “the crRNA Molecule or sgRNA molecule further comprises a repeat sequence portion of SEQ ID No 37 (claim 6).” The patent specifications, explains the crRNA comprises a guide portion “the DNA targeting RNA molecule is a crRNA molecule [column 10, line 3].”
The instant claim 1 continues “wherein the crRNA repeat sequence portion has at least 60-70%, 71-80%, 81-90%, 91- 95%, or 96-99% sequence identity to a mature OMNI-50 crRNA repeat sequence encoded by Ezakiella peruensis strain M6.X2 and is less than 17 nucleotides in length…” The patent similarly claims “a repeat sequence portion which comprises the sequence of SEQ ID NO: 37 (claim 6).” The patent claim recites SEQ ID NO 3, which anticipates current SEQ ID NO 1, which the current specification defines as a Ezakiella peruensis strain M6.X2 nuclease and the patent claim 6 recites crRNA 37, which anticipates current SEQ ID NO 24, which the current specification defines as an Ezakiella peruensis strain M6.X2 crRNA.
The instant claim 1 continues “wherein the RNA molecule forms a complex with and targets an OMNI-50 nuclease to a DNA target site in the presence of a tracrRNA sequence; and…” The patent similarly claims “the tracrRNA molecule comprises a nucleotide sequence that can form a complex with the CRISPR nuclease (claim 9)” and “a Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) nuclease comprising a sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 3. (claim 1).” OMNI-50 nuclease of the examined claim and application is represented by SEQ ID No 1 which matches the reference patent SEQ ID No 3 100%. Detailed support for crRNA-tracrRNA-nuclease-target DNA complex formation can be found in column 27, lines 26- 65 where the patent describes “CRISPR nuclease and a targeting molecule form a CRISPR complex that binds to a target DNA sequence.”
The instant claim 1 finishes “wherein the tracrRNA sequence is encoded by a tracrRNA portion of the RNA molecule or a tracrRNA portion of a second RNA molecule.” The patent similarly claims “the tracrRNA molecule or the sgRNA molecule further comprises a tracrRNA sequence portion which comprises one or more sequences selected from SEQ ID NOs: 38 (claim 7).” The crRNA SEQ ID No 24 of the examined claim and application matches the reference patent SEQ ID No 37 100%.
See the additional patented claims for additional limitations of the instant dependent claims 5, 7, 8, 9, and 10.
The instant claim 12 recites “A composition comprising a non-naturally occurring RNA molecule, the RNA molecule comprising a tracrRNA portion…” The patent similarly claims “A non-naturally occurring composition, (claim 1) and a CRISPR RNA (crRNA) molecule and a transactivating CRISPR RNA (tracrRNA) molecule, wherein the crRNA molecule, tracrRNA molecule, and the CRISPR nuclease do not naturally occur together (claim 2).”
The instant claim 12 continues “wherein the tracrRNA portion has at least 30-40%, 41-50%, 51- 60%, 61-70%, 71-80%, 81-90%, 91-95%, or 96-99% sequence identity to a mature OMNI-50 tracrRNA sequence encoded by Ezakiella peruensis strain M6.X2 and is less than 112 nucleotides in length…” The patent similarly claims “wherein the sgRNA molecule further comprises a nucleotide sequence portion which comprises a sequence selected from the group of sequences set forth as SEQ ID NOs: 44, (claim 8).” The SEQ ID No 126 of the examined claim and application matches 81.0% to the reference patent SEQ ID No 44. The applicant identifies SEQ ID No 126 as a tracrRNA.”
The instant claim 12 continues “wherein the RNA molecule forms a complex with and targets an OMNI-50 nuclease to a DNA target site in the presence of a crRNA repeat sequence portion and a guide sequence portion; and…” The patent similarly claims “the tracrRNA molecule comprises a nucleotide sequence that can form a complex with the CRISPR nuclease (claim 9);” and “the crRNA Molecule or sgRNA molecule further comprises a repeat sequence portion of SEQ ID No 37 (claim 6);” and “a Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) nuclease comprising a sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 3. (claim 1).” OMNI-50 nuclease of the examined claim and application is represented by SEQ ID No 1 which matches the reference patent SEQ ID No 3 100%. The crRNA SEQ ID No 24 of the examined claim and application matches the reference patent SEQ ID No 37 100%. Detailed support for crRNA-tracrRNA-nuclease-target DNA complex formation can be found in column 27, lines 26- 65 where the patent describes “CRISPR nuclease and a targeting molecule form a CRISPR complex that binds to a target DNA sequence.”
The instant claim 12 finishes “wherein the crRNA repeat sequence portion and the guide sequence portion are encoded by the RNA molecule or a second RNA molecule.” The patent similarly claims “the crRNA Molecule or sgRNA molecule further comprises a repeat sequence portion of SEQ ID No 37 (claim 6).” The specification provides explanation the crRNA includes a guide portion, “the DNA targeting RNA molecule is a crRNA molecule [column 10, line 3].”
See the additional patented claims for additional limitations of the instant dependent claims 16, 20, 22, 23, and 25- 27.
The instant claim 29 recites “A composition comprising a non-naturally occurring RNA molecule, the RNA molecule comprising an RNA scaffold portion…” The patent similarly claims “A non-naturally occurring composition (claim 1)”and “a CRISPR RNA (crRNA) molecule and a transactivating CRISPR RNA (tracrRNA) molecule, wherein the crRNA molecule, tracrRNA molecule, and the CRISPR nuclease do not naturally occur together; (claim 2).” The patent further provides details regarding scaffolds that “A skilled artisan will understand” beginning on column 27, line 26. The patent describes the “protein binding sequence” [line 35], the “RNA binding portion” [line 42], and a “nexus region and/or hairpin regions” [column 28, line 5].
The instant claim 29 continues “the RNA scaffold portion having the structure: crRNA repeat sequence portion - Linker portion - tracrRNA portion…” Referring to Fig 1B and 1C, the patent specification further provides evidence of the claimed scaffold “By shortening the duplex at the upper stem at different locations, the crRNA and tracrRNA were connected with tetra-loop 'gaaa', generating sgRNA scaffolds. (column 3, line 16)”
The instant claim 29 continues “wherein the crRNA repeat sequence portion has at least 60-70%, 71-80%, 81-90%, 91- 95%, or 96-99% sequence identity to a mature OMNI-50 crRNA repeat sequence encoded by Ezakiella peruensis strain M6.X2 and is less than 24 nucleotides in length; and …” The patent similarly claims “a repeat sequence portion which comprises the sequence of SEQ ID NO: 37 (claim 6)” and “the crRNA Molecule or sgRNA molecule further comprises a repeat sequence portion of SEQ ID No 37 (claim 6).” The crRNA SEQ ID No 24 of the examined claim and application matches the reference patent SEQ ID No 37 100%.
The instant claim 29 finishes “wherein the RNA scaffold portion forms a complex with and targets an OMNI-50 CRISPR nuclease to a DNA target site having complementarity to a guide sequence portion of the RNA molecule.” The patent similarly claims “the crRNA Molecule or sgRNA molecule further comprises a repeat sequence portion of SEQ ID No 37 (claim 6);” and “the tracrRNA molecule comprises a nucleotide sequence that can form a complex with the CRISPR nuclease. (claim 9).;” and “a Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) nuclease comprising a sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 3. (claim 1).” OMNI-50 nuclease of the examined claim and application is represented by SEQ ID No 1 which matches the reference patent SEQ ID No 3 100%. The specification provides explanation the crRNA includes a guide portion, “the DNA targeting RNA molecule is a crRNA molecule [column 10, line 3].”
See the additional patented claims for additional limitations of the instant dependent claims 16, 20, 22, 23, and 25- 27.
Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
The instant application fails to teach the genus of “mature crRNA repeat sequence” as described above. However the application distinctly describes several species of crRNA repeat sequences, for example instant SEQ ID No 24. When used as an example specie to reference prior art against, this examiner found the teachings of Chen. Chen (Chen US 2022/0064626 A1, effectively filed Feb 2, 2019) teaches a CRISPR nuclease gene editing platform with crRNA (scaffold RNA SEQ ID No 198) 80.0% match with instant application crRNA SEQ ID No 24, “scaffold sequences, the fragment of positions 1-12 (e.g., GUUUUAGAGCUA, SEQ ID NO:197; GUUUGAGAGCUA, SEQ ID NO: 198)” [0119].
This examiner was unable to find non-coowned prior art regarding OMNI-50 nuclease (SEQ ID No 1). OMNI-50 nuclease is incorporated into the claims, indefinitely in claim 1, and by SEQ ID No 1 in claim 10 among other claims. Zetsche does not qualify as prior art. The effectively filed date of Zetsche is March 23, 2021 whereas the effective filing date of the instant application is November 4, 2020. However, Zetsche (Zetsche US 20240167008 A1) teaches a SEQ ID No 14 that is 100% match to the instant application’s OMNI-50 nuclease SEQ ID No 1.
Conclusion
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/AARON DUREL WARD/Examiner, Art Unit 1636
/NEIL P HAMMELL/Supervisory Patent Examiner, Art Unit 1636
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