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 .
Election/Restrictions
Applicant’s election without traverse of Invention I and the species of H593 or D, and Domain G in the reply filed on 05 April 2026 is acknowledged. Claims 7, 38, 41, 44, 47, 50, 53, 56, 59-60, 75, and 84-86 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected Invention and species, there being no allowable generic or linking claim.
Claims 1-3 and 35 are pending and being examined on the merits.
Priority
The application is a 371 PCT of US2021/055851 filed 10/20/2021 which claims priority to applications 63/119,375 filed 11/30/2020, 63/117,163 filed 11/23/2020, and 63/094,535, filed 10/21/2020.
Information Disclosure Statement
The information disclosure statements filed 4/20/2023 and 09/08/2023 are acknowledged.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - This application contains sequence disclosures in accordance with the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 CFR 1.821 - 1.825.
The sequence disclosures are located in the drawings.
Required response – Applicant must provide:
A "Sequence Listing" part of the disclosure, as described above in item 1); as well as
An amendment specifically directing entry of the "Sequence Listing" part of the disclosure into the application in accordance with 1.825(b)(2);
A statement that the "Sequence Listing" includes no new matter in accordance with 1.825(b)(5); and
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(b)(4).
If the "Sequence Listing" part of the disclosure is submitted according to item 1) a) or b) above, Applicant must also provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter;
If the "Sequence Listing" part of the disclosure is submitted according to item 1) b), c), or d) above, Applicant must also provide:
A replacement CRF in accordance with 1.825(b)(6); and
Statement according to item 2) a) or b) above.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-2 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a CRISPR nuclease protein without significantly more. Claim 1 recite(s) non-naturally occurring composition comprising a CRISPR nuclease comprising a sequence having at least 90% identity to the amino acid sequence selected from the group consisting of SEQ ID NOs: 6, 1-5, and 7-8, or a nucleic acid molecule comprising a sequence encoding the CRISPR nuclease. The specification indicates that SEQ ID NO: 1-8 refers to the amino acid sequence of natural organisms [Table 1]. The specification teaches term "non-naturally occurring" or "engineered" indicates human manipulation and mean that the nucleic acid molecule or the polypeptide is at least substantially free from at least one other component with which they are naturally associated in nature and as found in nature [00225]. Therefore, a CRISPR nuclease comprising a sequence having at least 100% identity to the amino acid sequence selected from the group consisting of SEQ ID NOs: 6, 1-5, and 7-8 reads on a naturally occurring proteins.
It is noted that the claim refers to the nuclease as “non-natural”. However, the claim fails to specify how the term “non-natural” results in a markedly different characteristic. In addition, MPEP 2106.04(b) makes clear that even human-made products are not automatically eligible if they do not otherwise possess markedly different characteristics from their naturally occurring counterpart. Furthermore, there is no guidance in the specification for how SEQ ID NO: 6, 1-5, and 7-8 is non-natural in terms of a markedly different characteristic outside of stating the ability to codon optimize the DNA encoding the nuclease.
This judicial exception is not integrated into a practical application because the claim merely refers to the product of nature without markedly different characteristics.
For these reasons, the claim is directed to a product of nature.
The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception because there are no elements that are recited in addition to the nuclease.
Regarding claim 2, the claim requires the composition to further comprise an RNA molecule and the ability of the nuclease to form a complex with the RNA. The claim is silent as it relates to the RNA molecule and RNA molecules that bind to CRISPR nucleases occur in nature. The formation of the complex between the CRISPR nuclease and the RNA is a functional limitation, does not limit the structure of the CRISPR nuclease and RNA composition and therefore fails to recite a markedly different characteristic for the microbial cell.
Claim Rejections - 35 USC § 102
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 1 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by WP_120771636 (NCBI Reference Sequence: WP_120771636.1, type II CRISPR RNA-guided endonuclease Cas9 [Lactococcus allomyrinae], 10/9/2019).
WP_120771636.1 teaches a CRISPR RNA-guided endonuclease Cas9 sequence that is 100% identical to SEQ ID NO: 6.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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.
Claims 1-3 are rejected under 35 U.S.C. 103 as being unpatentable over WP_120771636 (NCBI Reference Sequence: WP_120771636.1, type II CRISPR RNA-guided endonuclease Cas9 [Lactococcus allomyrinae], 10/9/2019) in view of Hou (US 2019/0264232 A1).
Regarding claim 1, WP_120771636.1 teaches a CRISPR RNA-guided endonuclease Cas9 sequence that is 100% identical to SEQ ID NO: 6.
Regarding claims 2-3 WP_120771636.1 do not teach where the composition further comprises least one RNA molecule comprises a sequence selected from the group consisting of SEQ ID NOs: 139-160.
Hou teaches compositions and methods for novel Cas9 orthologs, including, but not limiting to, novel guide polynucleotide/Cas9 endonucleases complexes, single or dual guide RNAs, guide RNA elements, and Cas9 endonucleases [abstract]. Hou teaches a non-naturally occurring composition comprising a CRISPR nuclease. Hou teaches that Cas9 endonucleases and cognate guide RNAs are available for genome targeting, where the two components of Cas9 target site recognition, the PAM sequence and the guide RNA (either duplexed CRISPR RNA (crRNA) and trans-activating CRISPR RNA (tracrRNA) or chimeric fusion of crRNA and tracrRNA (single guide RNA (sgRNA), are established [0087]. Hou teaches SEQ ID NOs:171-255 are the crRNA repeat sequences corresponding to the Cas9 orthologs of SEQ IDs 86-170, respectively [0051]. SEQ ID NO: 198 comprises a sequence that is 100% identical toe SEQ ID NO: 139.
It would have been obvious to one ordinary skilled in the art before the effective filing date of the claimed invention to substitute the Cas9 nuclease of Hou with the CRISPR RNA-guided endonuclease Cas9 WP_120771636.1 where the Cas9 and crRNA of SEQ ID NO: 198 come together for the advantage of for genome targeting.
Claim 35 is rejected under 35 U.S.C. 103 as being unpatentable over WP_120771636 (NCBI Reference Sequence: WP_120771636.1, type II CRISPR RNA-guided endonuclease Cas9 [Lactococcus allomyrinae], 10/9/2019) in view of Hou (US 2019/0264232 A1) and further in view of Zetsche (20230279373 A1, filed 9/9/2020].
The teachings of WP_120771636.1 and Hou are discussed above as applied to claim 1 and similarly apply to claim 35.
WP_120771636.1 and Hou do not teach where the CRISPR nuclease is a nickase or a catalytically dead nuclease created by an amino acid substitution at H593 or N616.
Zetsche teaches identification of novel Cas9 enzymes for gene editing [0005]. Zetsche teaches that the Cas9 protein can have nickase activity [0011]. Zetsche teaches that two or more catalytic domains of Cas9 (RuvC1, RuvCII, RuvCIII) are mutated to produce an inactive, or "dead" Cas9 (dCas9) that lacks nucleic acid cleavage activity; where, the one or more mutations are in the PAM Interacting, HNH, and or the RuvC domains [0149]. Zetsche also teach where the Cas9 protein comprises one or more mutations at residues D8, H593, and/or N616; where the mutations inhibits the ability of Cas9 to cleave both strands of a DNA duplex and can create the Cas9 to an inactive or dead version of Cas9 [0150]. Zetsche teaches that dead Cas9 is used to specifically target effector proteins of various functions to specific nucleic acid target sites.
It would have been obvious to one ordinary skilled in the art before the effective filing date of the claimed invention to modify the Cas9 of WP_120771636 by introducing mutations into the catalytic residues of D8, H593, and/or N616 as taught by Zetsche, and any other residue, in order to reduce or abolish nuclease activity and generate nickase or catalytically dead Cas9 variants. One of ordinary skill would be motivated to make the modification for the advantage of using the nuclease for applications lacking double stranded activity such as targeting effector proteins of various function to specific nucleic acid target sites. Because Zetsche teaches that mutations in multiple catalytic domains of Cas9 may be combined to produce dead Cas9 variants, a person of skill in the art would had have a reasonable expectation that introducing substitutions into additional catalytic residues of the WP_120771636 Cas9 sequence, including residues D9, E503, H737 or D740 would predictably reduce or eliminate catalytic activity while preserving target recognition capability.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TIFFANY N GROOMS whose telephone number is (571)272-3771. The examiner can normally be reached M-F 830-530.
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/TIFFANY NICOLE GROOMS/Examiner, Art Unit 1637
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