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 .
Claim Status
Claims 1-3, 7-8, 12, 16-18, 20-21, 24, 26, 28-29, 32-34, 36, 38-39, 47, 49 and 51-58 are pending.
Claims 18, 20-21, 26, 28-29, 32-34, 36, 38-39, 47, 49 and 51-58 are withdrawn.
Claims 1-3, 7-8, 12, 16-17 and 24 are under examination.
Election/Restrictions
Applicant’s election of the following invention
Invention
Group I, claims 1-3, 7-8, 12, 16-17, 24, 33 and 39 directed to an engineered, non-naturally occurring composition comprising a Cas protein, wherein the Cas protein comprises an N-terminal X domain, a RuvC domain, and a Bridge Helix domain,
in the reply filed on 18th, May, 2026 is acknowledged.
Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
The requirement is still deemed proper and is therefore made FINAL.
Claims 18, 26, 28-29, 32, 34, 36, 38, 47, 49 and 51-58 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Applicant’s election of the following species
Species
A. Cas Protein Sequence of SEQ ID NO: 7 (claim 7)
B. Composition type of a nucleotide deaminase associated with or otherwise capable of forming a complex with the Cas protein (claim 24)
in the reply filed on 18th, May, 2026 is acknowledged. Claims 1-3, 7-8, 12, 16-17 and 24 encompass the elected species.
Because applicant did not distinctly and specifically point out the supposed errors in the species election requirement, the election has been treated as a species election without traverse (MPEP § 818.01(a)).
The requirement is still deemed proper and is therefore made FINAL.
Claims 33 and 39 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.
Species Rejoinder
The species election requirement between Cas protein sequence, as set forth in the Lack of Unity Mailed on 19th, March, 2026 has been reconsidered in view of the examination below, SEQ ID NO: 11 directed to previously non-elected species are no longer withdrawn from consideration.
In view of the above noted withdrawal of the species election requirement, applicant is advised that if any claim presented in a continuation or divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application.
Once a species election requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
Objections to Specification
Browser-Executable Code
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code.
Para. [0149]
www.novocraft.com
Para. [0181]
www.nature.com/nmeth/journal/v2/n6/full/nmeth763.html
www.nature.com/nchembio/j ournal/v8/n5/full/nchembio.922.html
www.pnas.org/content/104/3/1027.abstract
Para. [0182]
www.sciencemag.org/content/336/6081/604
Para. [0283]
www. kazusa.or.jp /codon/
Para. [0339]
www.biorxiv.org/content/10.1101/370460v1.full
Para. [0451]
www.genome.org/cgi/doi/10. 110 1/gr.173427. 114
Para. [0474]
www.interscience.wiley.com
Para. [0492]
www. intechopen. com/books/gene-therapy-app lications/delivery-methods-to-target-rnas-inthe- kidney
Para. [0666]
www.newphytologist.com
www.nature.con/naturecommunications
www.genome.arizona.edu/crispr/
Para. [0670]
www.biorxiv.org/content/10.1101/2020.04.11.037572v1
Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as “http://”, “www.” or other browser-executable code. See MPEP § 608.01.
Claim Objections
Claims 7-8, 12 and 24 are objected to because of the following informalities:
Claim 7 refers to the sequence identifiers rather than the sequences set forth in the sequence identifier. To overcome this objection, it is recommended that Applicant amend to refer to the sequences set forth in the sequence identifier, such as “sequence identity to a sequence comprising one of the sequences as set forth in SEQ ID NO:s 7-11.”
Claim 8 recites “wherein the composition further comprising” which is incorrectly conjugated and should recite “wherein the composition further comprises.”
Claim 8 recites “optionally wherein comprising” which is missing a subject and is also incorrectly conjugated. This should recite “wherein the composition further comprises.”
Claim 12 ends with two periods (“..”). It is recommended to amend the claim to end with one period.
Claim 24 includes periods before the end of the claim. Periods are only allowed at the end of a claim. Applicant is directed to MPEP 608.01(m) which states “Each claim begins with a capital letter and ends with a period. Periods may not be used elsewhere in the claims except for abbreviations. See Fressola v. Manbeck, 36 USPQ2d 1211 (D.D.C. 1995). Where a claim sets forth a plurality of elements or steps, each element or step of the claim should be separated by a line indentation, 37 CFR 1.75(i).”
To overcome this objection, it is recommended that Applicant amend all instances of periods before the end of the claim to parentheses (for example, “a.” would be amended to “a)” or “(a)”).
Appropriate correction is required.
Claim Interpretation
Instant claims recite “ Claims 1 and 3 recite “N-terminal X domain.” Claim 2 recites “C-terminal Y domain” and “Z domain.” These claimed limitations are given the broadest reasonable interpretation consistent with the specification as set forth below (see MPEP 2111).
N-terminal X domain
The instant specification describes the X domain (para. [0066-0068]). The specification states “X domains also include any polypeptides a structural similarity and/or sequence similarity to a X domain described in the art” (para. [0066]).
Therefore, the “N-terminal X domain” is interpreted to encompass a polypeptide domain on the N-terminal side that has a structural similarity and/or sequence similarity to an n-terminal domain described in the art.
C-terminal Y domain
The instant specification describes the Y domain (para. [0069-0071]). The specification states “The nucleic-acid guided nuclease comprises a C-terminal domain (also referred to herein as a Y domain)” (para. [0069]). The specification states “Y domain also include any polypeptides with a structural similarity and/or sequence similarity to a C-terminal domain described in the art” (para. [0070]).
Therefore, the “C-terminal Y domain” is interpreted to encompass a polypeptide domain on the C-terminal side that has structural similarity and/or sequence similarity to a C-terminal domain described in the art.
Z domain
The instant specification describes the Z domain (para. [0086-0088]). The specification states “the Z domain may be a domain sharing structural and/or sequence similarity with a Rec domain. The term "Rec domain" as referred to herein is indicative of a protein domain which may be part of a Rec lobe of a Cas protein, such as Cas9” (para. [0008]).
Therefore, the “Z domain” is interpreted to encompass a polypeptide domain that has structural and/or sequence similarity with a Rec domain.
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 1-3, 7-8 and 17 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a naturally occurring product without significantly more.
Applicant is directed to the 2019 Revised Patent Subject Matter Eligibility Guidance published in the Federal Register (84 FR 50) on 1/07/2019, which is found at: https://www.govinfo.gov/content/pkg/FR-2019-01-07/pdf/2018-28282.pdf; and the October 2019 Update: Subject Matter Eligibility, which is found at https://www.uspto.gov/sites/default/files/documents/peg_oct_2019_update.pdf.
Briefly summarized here, the new guidance cites a two part test: is the claimed invention directed to a statutory class of invention (Step 1), if so then is the claimed invention as a whole directed to a law of nature, natural phenomena, or an abstract idea (i.e. set forth or described in the claim) (Step 2A, prong one), if so then is the claimed invention recite additional elements that integrate the judicial exception into a practical application (Step 2A, prong two), if not then does the claim as a whole amount to significantly more than the judicial exception (Step 2B).
In regard to step 1, the claims are directed to a composition comprising a Cas protein, which is a product and is a statutory class of invention. Accordingly, the requirements of step 1 are met.
In regard to Step 2A prong one, as stated above, the claims are directed to a composition comprising a Cas protein.
Applicant is directed to the art of Nishimasu et al. (Cell. 2014 Feb 13;156(5):935–949.; henceforth “Nishimasu”). Nishimasu evidences the structure of a naturally occurring Cas protein (Streptococcus pyogenes Cas9) (Figure 1; see in particular Figure 1A which is copied below for reference).
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Regarding claim 1, the naturally occurring Cas9 protein evidenced by Nishimasu meets the structural limitations of instant claim because it comprises:
an N-terminal X domain (N terminal domains of the Cas9 including the RUVCI, REC1 or REC2 meet this limitations because they are “a polypeptide domain on the N-terminal side that has a structural similarity and/or sequence similarity to an n-terminal domain described in the art” as set forth in the claim interpretation above).
a RuvC domain (RUVCI, RUVCII or RUVCIII), and a
Bridge Helix domain (BH).
Regarding claim 2, the naturally occurring Cas9 protein evidenced by Nishimasu meets the structural limitations of instant claim because it further comprises:
further comprises a C-terminal Y domain (The c-terminal PI domain meets this limitation because it is has structural similarity and/or sequence similarity to a C-terminal domain described in the art, as set forth in the claim interpretation above) and/or an HNH domain;
wherein the RuvC domain comprises a RuvC I subdomain, a Ruv II subdomain and a Ruv III subdomain, and the HNH is located between the Ruv C II and RuvC III sub domains of the RuvC domain;
wherein the Cas protein further comprises a Z domain located between the RuvC-I and RuvC-II subdomains of the RuvC domain (the REC1 and/or the REC2 domains meet this limitation because they are “a polypeptide domain that has structural and/or sequence similarity with a Rec domain” as set forth in the claim interpretation above),
wherein the Z domain is from 100 to 200 amino acids in length (the REC2 domain, which meets this limitation for the reasons set forth above, is 128 amino acids long).
Regarding claim 3, the naturally occurring Cas9 protein evidenced by Nishimasu meets the structural limitations of instant claim because the N-terminal X domain, which is met by the structure of the N terminal domains of the Cas9 includes the option of the RUVC1 domain which is 60 amino acids long and is therefore no more than 70 amino acids long.
Regarding claim 7, the naturally occurring Cas9 protein evidenced by Nishimasu meets the structural limitations of instant claim because instant SEQ ID NO:11 is 100% identical to the Cas protein sequence of Streptococcus pyogenes Cas9. This is evidenced by NCBI Reference Sequence: WP_033888930.1 (accessed at: https://www.ncbi.nlm.nih.gov/protein/WP_033888930.1?report=genbank&log$=protalign&blast_rank=15&RID=2JWM2JTA014) which is a 100% match to instant SEQ ID NO: 11.
Regarding claim 17, the naturally occurring Cas9 protein evidenced by Nishimasu meets the structural limitations of instant claim the target sequence of Streptococcus pyogenes Cas9 includes a PAM of NGG (pg. 18 Figure 2).
Regarding claim 8, Applicant is directed to the art of Harrington et al. (Science. 2018 Nov 16;362(6416):839-842. Epub 2018 Oct 18.) and Ganguly et al. (Nat Commun. 2026 Jan 28;17(1):2126.; henceforth “Ganguly”). Harrington and Ganguly evidence Cas14, also known as Cas12f, which is a naturally occurring, small Cas protein that is 400-700 aa length (Harrington pg. 1 col. 1).
The Cas14 of Harrington and Ganguly meet the structural requirements of instant claims because it encompasses:
an N-terminal X domain (N terminal domains of the Cas14 meet this limitations because they are “a polypeptide domain on the N-terminal side that has a structural similarity and/or sequence similarity to an n-terminal domain described in the art” as set forth in the claim interpretation above);
a RuvC domain (Figure 1 of Harrinton); and
Bridge Helix domain (BH “Ganguly pg. 9 col. 1; Figure 5).
The Cas14 of Harrington also targets DNA and therefore meets the optional limitation of “optionally wherein the Cas protein targets DNA.”
In regard to Step 2A prong two, the judicial exception is not integrated into a practical application.
Specifically, claim 1 recites the additional elements of:
“engineered, non-naturally occurring composition”
Merely labeling the Cas as “engineered, non-naturally occurring” in the preamble does not integrate into a practical application because, as stated above, the structural limitations of the body of the claim are met by the naturally occurring Cas9 of Cas14 protein. Merely labeled it as an “engineered, non-naturally occurring composition” does not integrate the naturally occurring product into a practical application.
Claims 2-3 and 17 do not recite any additional elements.
Claim 8 recites the additional elements of “optionally wherein the composition further comprising a first and second nucleic acid molecules, the first and second nucleic acid molecules capable of forming a duplex, the duplex capable of forming a complex with the Cas protein, wherein the second nucleic acid molecule is a recombinant molecule comprising a heterologous guide sequence capable of directing site- specific binding of the complex to a target sequence of a target polynucleotide; optionally wherein comprising a single guide molecule capable of forming a complex with the Cas protein and directing site-specific binding of the complex to a target sequence of a target polynucleotide” which are optional embodiments and are not required structural elements of the claims. Therefore, because these elements are optional, they do not integrate the naturally occurring product into a practical application.
In regard to Step 2B, the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception. As stated above, instant claims are directed entirely to a structure of a Cas9 that is not markedly different than its naturally occurring counterpart. The only required additional element that is recited is the preamble of “engineered, non-naturally occurring” which does not amount to sufficiently more because the structure of the composition, as set forth in the body of the claim, is met by a naturally occurring Cas9 protein.
Therefore, the claims are directed to a naturally occurring product (Cas9 or Cas14 protein) that is not integrated into a practical application, does not include elements that amount to significantly more than the judicial exception, and do not qualify as patent eligible subject matter under 35 U.S.C. § 101.
Claim Rejections - 35 USC § 112(a)
Written Description
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 2-3 and 7-8 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.
The purpose of the written description requirement is to ‘ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent specification.” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (en banc) (quoting Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.04.
For a claim to a genus, a generic statement that defines a genus of substances by only their functional activity does not provide an adequate written description of the genus. Reagents of the University of California v. Eli Lilly, 43 USPQ2d 1398 (CAFC 1997).
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include a disclosure of a representative number of species to describe the complete structure of the claimed genus and/or disclosure of a complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, and any combination thereof.
Scope of the Claims
Instant claims encompass the following genera which present written description requirement issues.
“the Z domain is from 100 to 200 amino acids in length” (instant claim 2)
This encompasses all possible polypeptides of 100-200 amino acids in length. To illustrate the breadth of this genus, an estimation can be made using the 20 standard amino acids that this encompasses 20100 to 20200 possible structurally and functionally distinct polypeptides. Furthermore, because this additionally encompasses non-standard amino acids, the breadth of this limitation is much larger than this estimation. As such, this limitation encompasses an enormously broad number of structurally and functionally distinct polypeptides.
“the N-terminal X domain is no more than 70, preferably no more than 50 amino acids in length” (instant claim 3).
This encompasses all possible polypeptides of up to 70 or up to 50 amino acids in length. To illustrate the breadth of this genus, an estimation can be made using the 20 standard amino acids that this encompasses up to 2070 or 2050 possible structurally and functionally distinct polypeptides. Furthermore, because this additionally encompasses non-standard amino acids, the breadth of this limitation is much larger than this estimation. As such, this limitation encompasses an enormously broad number of structurally and functionally distinct polypeptides.
“a sequence with at least 80% sequence identity to a sequence comprising one of SEQ ID NOs. 7 or 11” (instant claim 7)
This encompasses all possible sequences of all possible lengths that are at least 80% identical to SEQ ID NO: 7 or SEQ ID NO: 11.
SEQ ID NO: 7 is 611 amino acids long, and SEQ ID NO: 11 is 1365 amino acids long. Therefore, instant claims encompass up to 122 or 273 mismatches respectfully in either of these sequences. To illustrate the breadth of this genus, an estimation can be made using the 20 standard amino acids and that with a mismatch, there would be 20 options (the 19 other standard amino acids or a deletion), therefore the breadth of this encompasses up to 12220 or 27320 structurally and functionally distinct polypeptides. Furthermore, because this additionally encompasses non-standard amino acids, the breadth of this limitation is much larger than this estimation. Additionally, instant claims also encompass fragments larger than SEQ ID NO: 7 or 11. As such, this limitation encompasses an enormously broad number of structurally and functionally distinct polypeptides.
“the Cas protein is no more than 500, no more than 600, no more than 700, or no more than 800 amino acids in length” (instant claim 8)
This encompasses all possible Cas proteins with all possible amino acid sequences of no more than 500, no more than 600, no more than 700, or no more than 800 amino acids in length that otherwise meet the claim limitations. Because claim 1, upon which claim 8 depends, requires, an N-terminal X domain, a RuvC domain, and a Bridge Helix domain, an estimate can be made that the N-terminal X domain can be any length (see claim interpretation above), the RuvC domain, and a Bridge Helix domain. From the art of Nishimasu et al. (Cell. 2014 Feb 13;156(5):935–949.; henceforth “Nishimasu”) an estimate can be made that a RuvC domain is 60 amino acids (RuvCI), and the Bridge Helix domain is 34 amino acids (BH), this leaves 406 to up to 706 amino acids that are not described for claim 8. Specifically, using the same estimations as above for the 406 to 706 amino acids, this encompasses up to 20406 to 20706 structurally and functionally distinct polypeptides. Furthermore, because this additionally encompasses non-standard amino acids, the breadth of this limitation is much larger than this estimation. As such, this limitation encompasses an enormously broad number of structurally and functionally distinct polypeptides.
Examiner’s Remark
It is noted that SEQ ID NO:s 8-10 of instant claim 7 are unelected species that are not currently under consideration. The breadth of these as claimed in in claim 7 present similar written description issues to the elected sequences discussed above.
Disclosure of Structure and Disclosure of Species
Z Domains
Regarding the Z domains, Applicant discloses Z domains in Table 1 which includes full length sequences of SEQ ID NO: 7-11.
Applicant discloses specific Z domains of SEQ ID NO: 19 and 20 which have a length of 155 and 153 amino acids respectfully.
In total, Applicant discloses 7 sequences that can be considered Z domains.
N-Terminal X Domains
Regarding the N-Terminal X domains, Applicant discloses X domains in Table 1 which includes full length sequences of SEQ ID NO: 7-11.
Applicant discloses specific X domains of SEQ ID NO: 13 and 14 which have a length of 34 and 42 amino acids respectfully.
In total, Applicant discloses 7 sequences that can be considered X domains.
80% Identity to SEQ ID NO: 7 or 11
Regarding the sequences with 80% sequence identity to a sequence comprising SEQ ID NO: 7 or 11, Applicant discloses the full length sequences of SEQ ID NO: 7 and SEQ ID NO: 11.
Cas Proteins No more than 500, 600, 700, or 800 amino acids in length
Regarding the Cas Proteins No more than 500, 600, 700, or 800 amino acids in length, Applicant discloses SEQ ID NO: 7, which is 611 amino acids in length and SEQ ID NO: 8 which is 625 amino acids in length.
In total, Applicant discloses 2 sequences which are Cas Proteins no more than 700, or 800 amino acids in length.
Applicant does not disclose any sequences which are Cas Proteins No more than 500 or 600 amino acids in length.
Structure/Function Correlation and Functional Characteristics
It is well known in the art that even a single amino acid change can affect the function of a protein, such as through a nonsense mutation that cause the protein to misfold and abrogate function. Therefore, Applicant’s claims, which encompass unfathomably large numbers of structurally distinct polypeptides also encompass unfathomably large numbers of functionally distinct polypeptides and domains.
Written Description – Conclusion
Conclusion
Therefore, the examiner concludes there is insufficient written description support for the instantly claimed genera.
Regarding the Z domains, Applicant discloses only 7 specific Z domain sequences, which is not representative of the unfathomably larger genus of Z domains from 100 to 200 amino acids in length that encompass structurally and functionally distinct polypeptide sequences and domains.
Regarding the N-terminal X domains, Applicant discloses only 7 specific X domain sequences, which is not representative of the unfathomably larger genus of N-terminal X domains no more than 70 or 50 amino acids lengths that encompass structurally and functionally distinct polypeptide sequences and domains.
Regarding the sequences 80% identical to SEQ ID NO: 7 or 11, Applicant discloses only 1 sequence each that meet this criteria which are the full length SEQ ID NO: 7 or 1 sequences. This is not representative of the full genus of sequences 80% identical to SEQ ID NO: 7 or 11, that encompass structurally and functionally distinct polypeptide sequences and Cas proteins.
Regarding the Cas proteins no more than, 500, 600, 700, or 800 amino acids in length, Applicant discloses only 2 sequences that are no more than 700 or 800 amino acids in length and Applicant discloses 0 sequences that are no more than 500 or 600 amino acids in length. This is not representative of the unfathomably large genus of Cas proteins no more than, 500, 600, 700, or 800 amino acids in length which encompasses structurally and functionally distinct polypeptides and Cas proteins.
There is no description of the structure/function correlation that would allow one of ordinary skill in the art to reasonably ascertain which substitutions, deletions or insertions can be performed. As such, one of ordinary skill in the art could not envision all the embodiments that fall outside of the description provide by the specification and the art.
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.
Claims 12 and 17 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.
Claim 12 recites “the nuclease domains of the Cas protein are catalytically inactive,” which claim 12 also recites “optionally wherein the nuclease domain has nickase activity or is engineered to have nickase activity.” Because nickase activity is a type of catalytic activity, it is unclear how the nuclease domains of the Cas protein can have no activity (“catalytically inactive” as claimed) and also have catalytic activity (“nickase activity” as claimed). Therefore, the scope of the claim is unclear and the metes and bounds of the claim are indefinite.
Claim 17 recites “the target sequence.” However, claim 1, upon which claim 17 depends, does not recite a target sequence. Therefore, there is improper antecedent basis for this term and the scope of the claim is indefinite because it is unclear how the target sequence is integrated into the structural requirements of claim1.
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.
Claims 1-3, 7 and 17 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Nishimasu et al. (Cell. 2014 Feb 13;156(5):935–949.; henceforth “Nishimasu”) as evidenced by NCBI Reference Sequence: WP_033888930.1 (accessed at: https://www.ncbi.nlm.nih.gov/protein/WP_033888930.1?report=genbank&log$=protalign&blast_rank=15&RID=2JWM2JTA014).
Regarding claim 1, Nishimasu discloses a composition comprising an N-terminal X domain (N terminal domains of the Cas9 including the RUVCI, REC1 or REC2 meet this limitations because they are “a polypeptide domain on the N-terminal side that has a structural similarity and/or sequence similarity to an n-terminal domain described in the art” as set forth in the claim interpretation above).
a RuvC domain (RUVCI, RUVCII or RUVCIII), and a
Bridge Helix domain (BH) (Figure 1; see in particular Figure 1A which is copied below for reference).
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Regarding claim 1, concerning the preamble of “engineered, non-naturally occurring,” this recites product-by process language. Applicant is reminded that product-by process claims are not limited by the manipulation of the recited steps, only the structure implied by the steps. “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (see MPEP 2113). In the instant case, the Cas9 protein of Nishimasu meets the structural limitations of instant claims for the reasons set forth above, and therefore meets instant claims.
Regarding claim 2, further to the discussion of claim 1 above, Nishimasu discloses the Cas9 protein further comprises a C-terminal Y domain (The c-terminal PI domain meets this limitation because it is has structural similarity and/or sequence similarity to a C-terminal domain described in the art, as set forth in the claim interpretation above) and/or an HNH domain;
wherein the RuvC domain comprises a RuvC I subdomain, a Ruv II subdomain and a Ruv III subdomain, and the HNH is located between the Ruv C II and RuvC III sub domains of the RuvC domain;
wherein the Cas protein further comprises a Z domain located between the RuvC-I and RuvC-II subdomains of the RuvC domain (the REC1 and/or the REC2 domains meet this limitation because they are “a polypeptide domain that has structural and/or sequence similarity with a Rec domain” as set forth in the claim interpretation above),
wherein the Z domain is from 100 to 200 amino acids in length (the REC2 domain, which meets this limitation for the reasons set forth above, is 128 amino acids long).
Regarding claim 3, further to the discussion of claim 1 above, the N-terminal X domain disclosed by Nishimasu, which is met by the structure of the N terminal domains of the Cas9 includes the option of the RUVC1 domain for the reasons set forth above, which is 60 amino acids long and is therefore no more than 70 amino acids long.
Regarding claim 7, the Cas9 protein evidenced by Nishimasu meets the structural limitations of instant claim because instant SEQ ID NO:11 is 100% identical to the Cas protein sequence of Streptococcus pyogenes Cas9. This is evidenced by NCBI Reference Sequence: WP_033888930.1 (accessed at: https://www.ncbi.nlm.nih.gov/protein/WP_033888930.1?report=genbank&log$=protalign&blast_rank=15&RID=2JWM2JTA014) which is a 100% match to instant SEQ ID NO: 11.
Regarding claim 17, the naturally occurring Cas9 disclosed by Nishimasu is Streptococcus pyogenes Cas9 which target includes a PAM of NGG (pg. 18 Figure 2).
Accordingly, Nishimasu anticipates instant claims.
Claims 1-2 and 8 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Harrington et al. (Science. 2018 Nov 16;362(6416):839-842. Epub 2018 Oct 18.) a evidenced by (Nat Commun. 2026 Jan 28;17(1):2126.; henceforth “Ganguly”).
Regarding claim 1, Harrington discloses Cas14, which meets the structural requirements of instant claims because it encompasses:
an N-terminal X domain (N terminal domains of the Cas14 meet this limitations because they are “a polypeptide domain on the N-terminal side that has a structural similarity and/or sequence similarity to an n-terminal domain described in the art” as set forth in the claim interpretation above);
a RuvC domain (Figure 1 of Harrinton); and
Bridge Helix domain (BH “Ganguly pg. 9 col. 1; Figure 5). Although Harrington does not explicitly state the Cas14 comprises a Bridge Helix domain, Ganguly evidences that Cas 14 (Cas12f) comprises a Bridge Helix domain (BH “Ganguly pg. 9 col. 1; Figure 5).
Regarding claim 2, further to the discussion of claim 1 above, Harrington discloses the Cas14 comprises an HNH domain (Figure 1).
Regarding claim 8, further to the discussion of claim 1 above, Harrison discloses the Cas14 protein is a small Cas protein that is 400-700 aa length (Harrington pg. 1 col. 1), which is encompassed by “no more than 500, no more than 600, no more than 700, or no more than 800 amino acids in length” as claimed.
Accordingly, Harrison as evidenced by Ganguly anticipates instant claims.
Claims 1-3, 7-8, 12, 16 and 24 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Zhang et al. (WO-2020191102-A1: Published 24th, September, 2020 with priority to U.S. Provisional application 62/820,109 filed on 18th, March, 2019; see IDS filed 20th, April, 2023; henceforth “Zhang1”).
Regarding claim 1, Zhang1 discloses an engineered, non-naturally occurring composition comprising a Cas protein (“a non-naturally occurring or engineered composition comprising a Type VII CRISPR effector protein” para. [0010]; see also para. [0016, 0060, 0070, 0164, 0169, 0246, 0258, 0271, 0280, 0324, 0332, 0351, 0390, 0394, 0424, 0556, 0690]; claim 1), wherein the Cas protein comprises
an N-terminal X domain (all other disclosed N terminal domains of the Cas meet this limitations because they are “a polypeptide domain on the N-terminal side that has a structural similarity and/or sequence similarity to an n-terminal domain described in the art” as set forth in the claim interpretation above),
a RuvC domain (para. [0007, 0018, 0020, 0025, 0028, 0049, 0051-0052, 0055, 0067, 0808, 01381-01383]; Numbered Aspects 3 and 5; claims 3 and 5; Figures 1, 4; Table 1).
and a Bridge Helix domain (para. [0018, 0020, 0025, 0051-0052, 0055, 01381-01382]; Numbered Aspect 3; claim 3; Figure 1; Table 1)
(see in particular SEQ ID NO: 1 which is a 100% match to instant SEQ ID NO:7; Example 1 of Zhang1).
Regarding claim 2, further to the discussion of claim 1 above, Zhang1 discloses the Cas protein further comprises a C-terminal Y domain (all other disclosed Y terminal domains of the Cas meet this limitations because they are a polypeptide domain on the C-terminal side that has structural similarity and/or sequence similarity to a C-terminal domain described in the art) and/or an HNH domain (para. [0007, 0018, 0020, 0025-0028, 0049, 0051-0052, 0055, 0067, 0808, 001381-001383]; Numbered Aspect 6; claim 6);
wherein the RuvC domain comprises a RuvC I subdomain, a Ruv II subdomain and a Ruv III subdomain (“the split RuvC domain comprises RuvC-I, RuvC-II, and/or RuvC-III” para, [0018]; claims 3 and 5);
wherein the Cas protein further comprises a Z domain located between the RuvC-I and RuvC-II subdomains of the RuvC domain (Rec domain; para. [0018-0019, 0051, 01381-01383]).
Regarding claim 3, further to the discussion of claim 1 above, Zhang1 discloses a sequence with an N-Terminal X domain which comprise “MPCHPARARELVRKGRAYWVKRDTVKLKTFLQNA” as an N-terminal X domain which is 34 amino acids (SEQ ID NO: 1 which is a 100% match to instant SEQ ID NO:7 and comprises “MPCHPARARELVRKGRAYWVKRDTVKLKTFLQNA” as an N-terminal X domain; Example 1 of Zhang1).
Regarding claim 7, further to the discussion of claim 1 above, Zhang1 discloses the Cas protein comprises a sequence with 100% sequence identity to a sequence comprising SEQ ID NO: 7 (SEQ ID NO: 1; Example 1 of Zhang1 is a 100% match to instant SEQ ID NO:7; see SCV RNG filed result 1).
Regarding claim 8, further to the discussion of claim 1 above, Zhang1 discloses the Cas protein comprises a sequence with 100% sequence identity to a sequence comprising SEQ ID NO: 7 (SEQ ID NO: 1; Example 1 of Zhang1 is a 100% match to instant SEQ ID NO:7; see SCV RNG filed result 1), which is 524 amino acids in length.
Regarding claim 12, further to the discussion of claim 1 above, Zhang1 discloses the nuclease domains of the Cas protein are catalytically inactive (para. [0012, 0018, 0051-0052, 0163-0164, 0171, 0177, 0171, 0178, 0180, 0185, 0225, 0226, 0234, 0246-0247]).
Zhang1 discloses the Cas protein further comprises a functional domain associated with the Cas protein with deaminase activity which is base editing activity (para. [0013, 0068-0070, 0073-0183, 0186-0238, 0254, 0268, 0523, 01040]; claims 19-21).
Zhang1 also discloses the nuclease domain has nickase activity or is engineered to have nickase activity (para. [0012]).
Regarding claim 16, further to the discussion of claim 1 above, Zhang1 discloses a homologous recombination donor template comprising a donor sequence for insertion into a target polynucleotide (“ donor polynucleotide” para. [0317]; “endogenous donor template mediated “ para. [0907]; see also para. [0555, 0907, 01048, 01050, 01053, 01056-01058, 01088, 01132, 001134, 01135]).
Regarding claim 24, further to the discussion of claim 1 above, Zhang1 discloses
as stated above (see claim 12 rejection above), the nuclease domains of the Cas protein are catalytically inactive (para. [0012, 0018, 0051-0052, 0163-0164, 0171, 0177, 0171, 0178, 0180, 0185, 0225, 0226, 0234, 0246-0247])
a nucleotide deaminase associated with or otherwise capable of forming a complex with the Cas protein (para. [0013, 0068-0070, 0073-0183, 0186-0238, 0254, 0268, 0523, 01040]; claims 19-21).
a single guide molecule capable of forming a complex with the Cas protein and directing site-specific binding at a target sequence (single guide RNA (sgRNA); para. [0045]; see also para. [0179, 0251, 0339, 0575-0576, 0753, 0827, 0847, 0927, 01189, 01207]).
Wherein the nucleotide deaminase is an adenosine deaminase or a cytidine
Deaminase (para. [0013, 0068-0070, 0073-0183, 0186-0238, 0254, 0268, 0523, 01040]; claims 19-21).
Accordingly, Zhang1 anticipates instant claims.
Examiner’s Remark
The prior art of Zhang et al. (WO-2020191102-A1: Published 24th, September, 2020 with priority to U.S. Provisional application 62/820,109 filed on 18th, March, 2019) applied above is prior art under both 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) . WO-2020191102-A1is published 24th, September, 2020 which pre-dates the effective filing date of the instant Application of 23rd, October, 2020 and it is therefore prior art under 35 U.S.C. 102(a)(1). WO-2020191102-A1 is also a WIPO publication by another inventor that designates the United States and was effectively filed 18th, March, 2019) which is before the effective filing date of the claimed invention and it is therefore prior art under 35 U.S.C. 102(a)(2). To overcome this rejection, Applicant will need to overcome both the rejection 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Zhang1.
Claims 1-3, 7-8, 12, 17 and 24 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Maianti et al. (WO-2018/165631-A1; henceforth “Maianti”) as evidenced by Nishimasu et al. (Cell. 2014 Feb 13;156(5):935–949.; henceforth “Nishimasu”).
Regarding claims 1 and 7, Maianti discloses compositions comprising Cas sequences comprising S. Pyogenes Cas 9 (SEQ ID NO: 1 claim 9; Example 1 SEQ ID NO:s 11, 259 which are 100% identical to instant SEQ ID NO: 11) that is 100% identical to instant SEQ ID NO: 11.
Regarding claim 1, the S. Pyogenes Cas 9 of Maianti comprises an
N-terminal X domain (N terminal domains of the Cas9 meet this limitations because they are “a polypeptide domain on the N-terminal side that has a structural similarity and/or sequence similarity to an n-terminal domain described in the art” as set forth in the claim interpretation above).,
a RuvC domain (para. [0119, 0128-0130, 0209-0210, 0219, 0236, 0309],
and a Bridge Helix domain (although Maianti does not specifically recite a Bridge helix domain, this is evidenced by Nishimasu as a structure of S. Pyogenes Cas9 (Figure 1A).
As stated above, Maianti also discloses Cas sequences comprising S. Pyogenes Cas 9 (SEQ ID NO: 1 claim 9; Example 1 SEQ ID NO:s 11, 259) which are 100% identical to instant SEQ ID NO: 11, which is a specific species that comprises the domains of claim 1.
Regarding claim 1, concerning the preamble of “engineered, non-naturally occurring,” this recites product-by process language. Applicant is reminded that product-by process claims are not limited by the manipulation of the recited steps, only the structure implied by the steps. “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (see MPEP 2113). In the instant case, the Cas9 protein of Maianti meets the structural limitations of instant claims for the reasons set forth above, and therefore meets instant claims.
Regarding claim 2, further to the discussion of claim 1 above, the S. Pyogenes Cas9 protein disclosed by Maianti is evidenced by Nishimasu to
further comprise a C-terminal Y domain (The c-terminal PI domain meets this limitation because it is has structural similarity and/or sequence similarity to a C-terminal domain described in the art, as set forth in the claim interpretation above) and/or an HNH domain;
wherein the RuvC domain comprises a RuvC I subdomain, a Ruv II subdomain and a Ruv III subdomain, and the HNH is located between the Ruv C II and RuvC III sub domains of the RuvC domain;
wherein the Cas protein further comprises a Z domain located between the RuvC-I and RuvC-II subdomains of the RuvC domain (the REC1 and/or the REC2 domains meet this limitation because they are “a polypeptide domain that has structural and/or sequence similarity with a Rec domain” as set forth in the claim interpretation above),
wherein the Z domain is from 100 to 200 amino acids in length (the REC2 domain, which meets this limitation for the reasons set forth above, is 128 amino acids long).
Regarding claim 12, further to the discussion of claim 1 above, Maianti discloses the nuclease domains of the Cas protein are catalytically inactive (“dCas9” para. [0128]; see also para. [0007-0008, 0129-0130, 0135, 0205-0208, 0235, 0245, 0247, 0254, 0259, 0307]).
Regarding claim 12, Maianti also discloses the nuclease domain has nickase activity or is engineered to have nickase activity (para. [0004, 0129-0131, 0135, 0205-0206, 0208, 0236]).
Regarding claim 12, Maianti discloses the Cas further comprises functional domain associated with the Cas protein with deaminase base editing activity (“cytosine deaminase” abstract; see also para. [0004-0005, 0010-0012, 0061, 0069-0072, 0131-0134, 0137, 0145, 0171, 0204, 0230, 0237-0247, 0254-0257, 0259-0260, 0306, 0312, 0326]; claims 1, 14-16, 18, 20, 22-24, 186, 193-194, 205-207).
Regarding claim 17, further to the discussion of claim 1 above, a PAM of NGG in the target sequence is an inherent property of the S. Pyogenes Cas9 disclosed by Maianti. Nishimasu evidences S. Pyogenes Cas9 targets PAM of NGG (pg. 18 Figure 2).
Regarding claim 24, further to the discussion of claim 1 above, Maianti discloses
the Cas protein is catalytically inactive (“dCas9” para. [0128]; see also para. [0007-0008, 0129-0130, 0135, 0205-0208, 0235, 0245, 0247, 0254, 0259, 0307]) (see claim 12 rejection above),
a nucleotide deaminase associated with or otherwise capable of forming a complex with the Cas protein wherein the nucleotide deaminase is a cytidine deaminase (“cytosine deaminase” abstract; see also para. [0004-0005, 0010-0012, 0061, 0069-0072, 0131-0134, 0137, 0145, 0171, 0204, 0230, 0237-0247, 0254-0257, 0259-0260, 0306, 0312, 0326]; claims 1, 14-16, 18, 20, 22-24, 186, 193-194, 205-207) (see claim 12 rejection above),
a single guide molecule capable of forming a complex with the Cas protein and directing site-specific binding at a target sequence (para. [0118, 0129, 0210, 0265-0267])
Claims 1-3, 7, 12, and 16-17 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Jaskula-Ranga et al. (WO-2018009534-A1; henceforth “Jaskula-Ranga”) as evidenced by Nishimasu et al. (Cell. 2014 Feb 13;156(5):935–949.; henceforth “Nishimasu”).
Regarding claims 1 and 7, Jaskula-Ranga discloses compositions comprising Cas9 sequences from S. Pyogenes (pg. 2, 17, 20, 41, 48-50, 85) including specifically SEQ ID NO: 51 which is a 100% match to instant SEQ ID NO: 11 (instant claim 7).
Regarding claim 1, Nishimasu evidences the S. Pyogenes Cas9 protein comprises an N-terminal X domain (N terminal domains of the Cas9 including the RUVCI, REC1 or REC2 meet this limitations because they are “a polypeptide domain on the N-terminal side that has a structural similarity and/or sequence similarity to an n-terminal domain described in the art” as set forth in the claim interpretation above).
a RuvC domain (RUVCI, RUVCII or RUVCIII), and a
Bridge Helix domain (BH) (Figure 1 of Nishimasu; see in particular Figure 1A which is copied below for reference).
PNG
media_image1.png
185
1165
media_image1.png
Greyscale
Regarding claim 1, concerning the preamble of “engineered, non-naturally occurring,” this recites product-by process language. Applicant is reminded that product-by process claims are not limited by the manipulation of the recited steps, only the structure implied by the steps. “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (see MPEP 2113). In the instant case, the Cas9 protein of Jaskula-Ranga meets the structural limitations of instant claims for the reasons set forth above, and therefore meets instant claims.
Regarding claim 2, further to the discussion of claim 1 above, Nishimasu evidences the Cas9 protein of S. Pyogenes further comprises a C-terminal Y domain (The c-terminal PI domain meets this limitation because it is has structural similarity and/or sequence similarity to a C-terminal domain described in the art, as set forth in the claim interpretation above) and/or an HNH domain;
wherein the RuvC domain comprises a RuvC I subdomain, a Ruv II subdomain and a Ruv III subdomain, and the HNH is located between the Ruv C II and RuvC III sub domains of the RuvC domain;
wherein the Cas protein further comprises a Z domain located between the RuvC-I and RuvC-II subdomains of the RuvC domain (the REC1 and/or the REC2 domains meet this limitation because they are “a polypeptide domain that has structural and/or sequence similarity with a Rec domain” as set forth in the claim interpretation above),
wherein the Z domain is from 100 to 200 amino acids in length (the REC2 domain, which meets this limitation for the reasons set forth above, is 128 amino acids long).
Regarding claim 3, further to the discussion of claim 1 above, the N-terminal X domain of the S. Pyogenes Cas9 disclosed by Jaskula-Ranga as evidenced by Nishimasu, which is met by the structure of the N terminal domains of the Cas9 includes the option of the RUVC1 domain for the reasons set forth above, which is 60 amino acids long and is therefore no more than 70 amino acids long.
Regarding claim 12, further to the discussion of claim 1 above, Jaskula-Ranga discloses the nuclease domains of the Cas protein are catalytically inactive (dCas9 (nuclease-dead version of Cas9) pg. 16; Figure 13). Jaskula-Ranga also discloses the nuclease domain has nickase activity or is engineered to have nickase activity (pg. 18, 30, 61, 77; Figure 25; claim 103).
Regarding claim 16, further to the discussion of claim 1 above, Jaskula-Ranga discloses a homologous recombination donor template comprising a donor sequence for insertion into a target polynucleotide (abstract; pg. 4, 10-11, 21, 31, 61, 139, 172).
Regarding claim 17, further to the discussion of claim 1 above, a PAM of NGG in the target sequence is an inherent property of the S. Pyogenes Cas9 disclosed by Jaskula-Ranga. Nishimasu evidences S. Pyogenes Cas9 targets PAM of NGG (pg. 18 Figure 2).
Accordingly, Jaskula-Ranga as evidenced by Nishimasu, anticipates instant claims.
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.
Non-Statutory Double Patenting
Claims 1-3, 7-8, 12, 16-17 and 24 are rejected on the ground of nonstatutory double patenting as being unpatentable over the following claims of the following issued US patents because they claim a composition comprising a Cas protein or Cas effector protein in the identified claims that meets the structural requirements of instant claims or make obvious the instant claims.
Claims 1-3, 7-8 12, 16-17 and 24 of the instant application conflict with these claims of these U.S. Patents:
US Patent No:
12644111 (claims 1, 14 and 18)
12618101 (claims 1 and 11)
12595478 (claims 4, 18, 20, 22)
12559786 (claim 30)
12534714 (claim 1)
12529042 (claims 1-2)
12522807 (claim 1)
12467925 (claims 1 and 18-19)
12435320 (claims 1, 23 and 29)
12431216 (claim 1)
12421507 (claims 1 and 16-19)
12415000 (claim 1)
12410416 (claims 1, 16 and 21)
12350368 (claim 9)
12351837 (claim 8)
12297436 (claim 1)
12252705 (claim 1)12227742 (claim 1)
12221636 (claims 6-8)
12215318 (claims 1, 15 and 23)
12188059 (claim 1)
12110490 (claim 1)
12054755 (claim 1)
11965159 (claim 16)
11913044 (claims 14-15)
11898142 (claims 1-2)
11866697 (claim 22)
11840711 (claim 1)
11788083 (claim 1)
11767528 (claim 1)
12297433 (claim 1)
11730826 (claim 1)
11732274 (claims 20-23)
11633732 (claim 1)
11618928 (claim 1)
11618896 (claim 1)
11597919 (claim 11)
11578312 (claim 20)
11530425 (claim 1)
12146152 (claims 1 and 6)
11453865 (claims 1-2)
11697808 (claims 1-2)
12385024 (claim 1)
11453907 (claim 1)
11639523 (claim 1)
12522863 (claim 4)
11795452 (claim 1)
12509680 (claim 1)
12570972 (claims 1, 25 and 27)
12624354 (claims 1 and 25)
11384344 (claim 1)
12559774 (claims 18-19 and 24-26)
11286478 (claim 1)
12344838 (claim 9)
11180751 (claim 1)
11174515 (claim 1)
11091798 (claim 1)
11634755 (claim 1)
11773432 (claim 1)
12091709 (claim 18)
12371737 (claim 1)
11060115 (claims 1 and 3)
11773412 (claim 1)
11021740 (claim 1)
12630867 (claim 1)
10954514 (claims 12-13)
10876100 (claims 1 and 25)
12123032 (claims 1, 8 , 10 and 12)
10851357 (claims 1 and 21)
12553065 (claim 1)
10696986 (claim 1)
10377998 (claim 1)
10266886 (claims 1 and 9)
12037639 (claim 1)
9790490 (claims 1-4)
8993233 (claim 43)
8906616 (claim 1)
8889356 (claim 24)
8932814 (claim 25)
8865406 (claim 24)
8889418 (claims 1 and 23)
8895308 (claim 25)
8795965 (claim 26)
8871445 (claim 26)
8697359 (claim 15)
8771945 (claim 26)
8945839 (see IDS filed 29th, September, 2026;claim 21)
12473543 (claims 10-11)
12435330 (claims 6-9)
11912985 (claim 1)
10494621 (claims 1-3)
Although the claims in the cited Patents above are not identical, they are not patentably distinct for the reasons stated below.
Claims 1-3, 7 and 17 are rejected on the ground of nonstatutory double patenting as being unpatentable over the cited claims of the issued US patents listed above, as evidenced by Nishimasu et al. (Cell. 2014 Feb 13;156(5):935–949.; henceforth “Nishimasu”) and NCBI Reference Sequence: WP_033888930.1 (accessed at: https://www.ncbi.nlm.nih.gov/protein/WP_033888930.1?report=genbank&log$=protalign&blast_rank=15&RID=2JWM2JTA014) because they claim a composition comprising a Cas protein or Cas effector protein in the identified claims that meets the structural requirements of instant claims or make obvious the instant claims.
Regarding claim 1, the claim requires the structure of a Cas protein, wherein the Cas protein comprises an N-terminal X domain, a RuvC domain, and a Bridge Helix domain. As set forth above, all possible N terminal domains of the Cas meet the limitation of an N-Terminal X domain because they are “a polypeptide domain on the N-terminal side that has a structural similarity and/or sequence similarity to an n-terminal domain described in the art” as set forth in the claim interpretation above. As set forth above, Cas proteins comprise a RuvC domain, and a Bridge Helix domain.
Regarding claim 1, the preamble of “engineered, non-naturally occurring,” this recites product-by process language (see MPEP 2113). Cas proteins or effector proteins meets the structural limitations of instant claims for the reasons set forth above, and therefore meet instant claims.
Instant claim 2 requires the Cas protein further comprises a C-terminal Y domain and/or an HNH domain. HNH domains are inherently comprised by Cas proteins or effector proteins and all possible C-terminal domains meet the limitations of a C Terminal Y-domain because they have structural similarity and/or sequence similarity to a C-terminal domain described in the art, as set forth in the claim interpretation above.
Regarding claim 3, as set forth above, the Cas proteins evidenced by Nishimasu et al. (Cell. 2014 Feb 13;156(5):935–949.; henceforth “Nishimasu”), meets the structural limitations of instant claim because the N-terminal X domain, which is met by the structure of the N terminal domains of the Cas9 includes the option of the RUVC1 domain which is 60 amino acids long and is therefore no more than 70 amino acids long.
Therefore, instant claims 1-3, as presently claimed, presents a non-statutory double patenting issue with any claim that is drawn to a composition that comprises a Cas, Cas9 or effector protein.
Regarding claim 7, as set forth above, instant SEQ ID NO: 11 is 100% identical to the sequence of Cas9, as evidenced by NCBI Reference Sequence: WP_033888930.1.
Regarding claim 17, as stated above, a PAM of NGG is an inherent property of Cas9.
Therefore, instant claims 7 and 17 presents a non-statutory double patenting issue with any claim that comprises or encompasses a Cas9 protein.
Therefore, because the instant Application claims are anticipated by or obvious over the cited patent claims, as evidenced by Nishimasu and WP_033888930.1., said claims are not patentably distinct.
Claim 8 is rejected on the ground of nonstatutory double patenting as being unpatentable over the cited claims of the issued US patents listed above, as evidenced by Nishimasu et al. (Cell. 2014 Feb 13;156(5):935–949.; henceforth “Nishimasu”) and NCBI Reference Sequence: WP_033888930.1 (accessed at: https://www.ncbi.nlm.nih.gov/protein/WP_033888930.1?report=genbank&log$=protalign&blast_rank=15&RID=2JWM2JTA014) and further evidenced by Harrington et al. (Science. 2018 Nov 16;362(6416):839-842. Epub 2018 Oct 18.), because they claim a composition comprising a Cas protein or Cas effector protein in the identified claims that meets the structural requirements of instant claims or make obvious the instant claims.
The teachings of the cited U.S. patents above, Nishimasu, and WP_033888930.1 are incorporated herein in their entirety.
Regarding claim 8, as set forth above, Cas14 (also known as Cas12f) meets the structural requirements of instant claims because it is a small Cas protein of 400-700 amino acids in length Harrington evidence Cas14, also known as Cas12f, which is a naturally occurring, small Cas protein that is 400-700 aa length (Harrington pg. 1 col. 1).
Therefore, instant claim 8 presents a non-statutory double patenting issue with a claim drawn to a composition that comprises or encompasses a Cas14 or Cas12f protein, or otherwise meets the length requirements of the claim.
Additionally, regarding claim 8, the N-terminal X domain can be of any length and Nishimasu evidences RuvC domains of RuvC1 of 60 amino acids, and BH domain of 34 amino acids, which requires a length of 93 amino acids and some length of N-terminal X domain. Therefore, Cas proteins and effector protein claims that also encompass these elements encompass embodiments of instant claims that are less than 500, 600, 700, or 800 amino acids.
Claims 12 and 24 are rejected on the ground of nonstatutory double patenting as being unpatentable over the cited claims of the issued US patents listed above, as evidenced by Nishimasu et al. (Cell. 2014 Feb 13;156(5):935–949.; henceforth “Nishimasu”) and NCBI Reference Sequence: WP_033888930.1 (accessed at: https://www.ncbi.nlm.nih.gov/protein/WP_033888930.1?report=genbank&log$=protalign&blast_rank=15&RID=2JWM2JTA014) as applied to claim 1 above, and in further view of Maianti et al. (WO-2018/165631-A1; henceforth “Maianti”) because they claim a composition comprising a Cas protein or Cas effector protein in the identified claims that meets the structural requirements of instant claims or make obvious the instant claims.
The teachings of the cited U.S. patents above, Nishimasu, and WP_033888930.1 are incorporated herein in their entirety.
Regarding claims 12 and 24, Maianti teaches compositions where the domains of the Cas protein are catalytically inactive (“dCas9” para. [0128]; see also para. [0007-0008, 0129-0130, 0135, 0205-0208, 0235, 0245, 0247, 0254, 0259, 0307]) (instant claim 12), Maianti teaches nucleotide deaminase associated with or otherwise capable of forming a complex with the Cas protein wherein the nucleotide deaminase is a cytidine deaminase (“cytosine deaminase” abstract; see also para. [0004-0005, 0010-0012, 0061, 0069-0072, 0131-0134, 0137, 0145, 0171, 0204, 0230, 0237-0247, 0254-0257, 0259-0260, 0306, 0312, 0326]; claims 1, 14-16, 18, 20, 22-24, 186, 193-194, 205-207) (instant claims 12 and 24), and Maianti teaches a single guide molecule capable of forming a complex with the Cas protein and directing site-specific binding at a target sequence (para. [0118, 0129, 0210, 0265-0267]) (instant claim 24). It would be obvious to combine these known prior art elements because Maianti teaches including these to edit selected target sites by nucleobase editors (abstract) and to introduce targeted mutations into tumor-specific antigens (para. [0004]), and also provides a reasonable expectation of success in preparing such a composition (Examples 1-2).
Therefore, in view of Maianti, instant claims 12 and 24 are obvious.
Claim 16 is rejected on the ground of nonstatutory double patenting as being unpatentable over the cited claims of the issued US patents listed above, as evidenced by Nishimasu et al. (Cell. 2014 Feb 13;156(5):935–949.; henceforth “Nishimasu”) and NCBI Reference Sequence: WP_033888930.1 (accessed at: https://www.ncbi.nlm.nih.gov/protein/WP_033888930.1?report=genbank&log$=protalign&blast_rank=15&RID=2JWM2JTA014) as applied to claim 1 above, and in further view of Jaskula-Ranga et al. (WO-2018009534-A1; henceforth “Jaskula-Ranga”) because they claim a composition comprising a Cas protein or Cas effector protein in the identified claims that meets the structural requirements of instant claims or make obvious the instant claims.
The teachings of the cited U.S. patents above, Nishimasu, and WP_033888930.1 are incorporated herein in their entirety.
Regarding claim 16, Jaskula-Ranga teaches a composition with a Cas protein and a homologous recombination donor template comprising a donor sequence for insertion into a target polynucleotide (abstract; pg. 4, 10-11, 21, 31, 61, 139, 172). It would be obvious to combine these known prior art elements because Jaskula-Ranga teaches including the donor template for correcting mutations (abstract), and also provides a reasonable expectation of success in preparing such a composition (Examples 1-3).
Therefore, in view of Jaskula-Ranga, instant claims 16 is obvious.
Provisional Non-Statutory Double Patenting
Claims 1-3, 7-8, 12, 16-17 and 24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the following claims of the following co-pending Applications because they claim composition comprising a Cas protein or Cas effector protein in the identified claims that meets the structural requirements of instant claims or make obvious the instant claims for the reasons set forth below.
Claim 8 is specifically provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 17/612,504 for the reasons set forth below.
The date of the specific conflicting claim set reviewed in this office action is noted.
Applications which list Feng Zhang as an Inventor:
19/677,353 (claim 1; claims filed 14th, May, 2026)
19/563,393 (claims 1 and 8; claims filed 28th, April, 2026)
19/388,533 (claims 1, 21-22, 24, 28, 30, 34, 71, 75, 83, 86, 105, 127, 137, 140; claims filed 5th, January, 2026)
19/361,664 (claim 31; claims filed 8th, April, 2026)
19/348,206 (claim 1; claims filed 12th, January, 2026)
19/342,889 (claims 1 and 24; claims filed 29th, September, 2025)
19/330,290 (claim 1 and 20; claims filed 16th, September, 2025)
19/307,262 (claim 2, 16 and 19-20; claims filed 25th, February, 2026)
19/287,917 (claim 1, 18, 21, 24, 61, 64, 67; claims filed 7th, October, 2025)
19/262,704 (claims 24, 39, 41-42; claims filed 20th, November, 2025)
19/260,968 (claims 9 and 20; claims filed 23rd, February, 2026)
19/221,936 (claim 2 and 26; claims filed 9th, January, 2026)
19/089,389 (claims 1, 15 and 17; claims field 2nd, June, 2025)
19/053,983 (claims 157-158, 162; claims filed 1st, October, 2025)
19/043,619 (claims 8 and 26; claims filed 10th, April, 2025)
19/028,841 (claims 2 and 20-21; claims filed 27th, April, 2025)
19/029,037 (claims 2 and 20-21; claims filed 27th, April, 2025)
19/025,663 (claim 1; claims filed 16th, January, 2025)
19/016,260 (claims 1, 14, 20-22; claims filed 31st, March, 2025)
18/932,763 (claims 7-8, 32-33; claims filed 13th, January, 2025)
18/905,630 (claims 105, 119, 121-122; claims filed 26th, February, 2025)
18/889,942 (claims 90 and 95; claims filed 24th, March, 2025)
18/772,681 (claim 1; claims filed 6th, March, 2025)
18/726,514 (claims 19 and 39; claims filed 27th, January, 2025)
18/717,020 (claims 1, 7-8, 21, 27, 40; claims filed 19th, December, 2024)
18/712,779 (claims 1 and 22; claims filed 6th, December, 2024)
18/701,358 (claims 1 and 13; claims filed 5th, November, 2024)
18/235,760 (claim 62; claims filed 20th, February, 2024)
18/317,248 (claims 64-67; claims filed 9th, February, 2024)
18/107,108 (claim 41; claims filed 4th, August, 2024)
17/910,497 (claim 1; claims filed 3rd, March, 2026)
17/640,016 (claims 1 and 11; claims filed 12th, May, 2026)
17/638,355 (claims 1, 15, 20-21; claims filed 13th, February, 2026)
17/612,245 (claims 1 and 26; claims filed 24th, March, 2026)
17/321,872 (claim 1; claims filed 11th, May, 2026)
16/973,061 (claim 71; claims filed 8th, May, 2026)
16/631,879 (claim 1; claims filed 21st, April, 2026)
16/617,560 (claim 1; claims filed 26th, March, 2026)
16/450,852 (claim 16, claims filed 5th, June, 2026)
18/965,935 (claims 1 and 4-17; claims filed 26th, March, 2026)
18/726,460 (claims 27, 33 and 56; claims filed 21st, January, 2025)
18/276,471 (claims 2-3, 14 and 23-25; claims filed 17th, April, 2026)
18/272,158 (claims 21 and 48; claims filed 22nd, April, 2026)
18/270,854 (claims 8, 10-14, 17; claims filed 19th, March, 2026)
18/269,813 (claims 1 and 34; claims filed 13th, March, 2026)
17/801,815 (claims 1-2, 18 and 60; claims filed 6th, April, 2026)
17/742,503 (claim 29, claims filed 24th, October, 2022)
17/742,127 (claims 1-2; claims filed 7th, October, 2022)
17/763,907 (claims 7 and 98-99; claims filed 2nd March, 2026)
17/612,504 (claims 1 and 41-44; note that claim 1 also specifically meets instant claim 8 because the cas protein is between 600-750 amino acids in size; claims filed 2nd, January, 2026)
16/961,820 (claim 1; claims filed 16th, March, 2026)
16/955,380 (claim 1; claims filed 29th, April, 2026)
16/954,032 (claim 1; claims filed 26th, January, 2026)
16/772,269 (claim 1; claims filed 18th, February, 2026)
16/626,396 (claims 23, 66 and 69; claims filed 6th, February, 2026)
17/831,745 (claim 31; claims filed 17th, February, 2026)
18/349,707 (claim 51; claims filed 28th, January, 2026)
18/334,074 (claim 1; claims filed 29th, May, 2026)
17/798,248 (claims 19 and 21; claims filed 18th, March, 2026)
17/793,115 (claims 1, 33, 40 and 43; claims filed 24th, February, 2026)
17/786,168 (claim 1; claims filed 21st, January, 2026)
17/776,269 (claims 1, 48, 56; claims filed 9th, January, 2026)
17/761,641 (claims 30, 73, 83; claims filed 30th, January, 2026)
17/439,063 (claim 1; claims filed 4th, March, 2025)
17/273,999 (claims 16, 25-27, 31-33; claims filed 22nd, January, 2026)
17/264,340 (claims 4, 8 and 17; claims filed 21st, April, 2026)
18/248,252 (claims 4, 19, 23; claims filed 27th, January, 2026)
17/928,355 (claims 1, 21; claims filed 26th, May, 2026)
17/785,070 (claims 7-11; claims filed 4th, May, 2026)
17/761,292 (claims 1, 24, 27, 31, 42, 44-45, 48; claims filed 1st, May, 2026)
17/254,886 (claim 41; claims filed 27th, April, 2026)
16/756,134 (claims 1, 46-47; claims filed 26th, May, 2026)
16/095,207 (claims 1-2; claims filed 26th, May, 2026)
15/330,876 (claims 1, 30 and 40; claims filed 18th, May, 2020)
14/738,398 (claim 1; claims filed 26th, March, 2022)
17/773,104 (claims 1, 14, 34; claims filed 4th, June, 2026)
18/480,647 (claim 1; claims filed 18th, March, 2026). A notice of allowance as mailed on 31st, March, 2026. When the Patent issues this rejection will no longer be provisional.
17/495,219 (claim 1; claims filed 13th, April, 2026) A notice of allowance as mailed on 24th, April, 2026. When the Patent issues this rejection will no longer be provisional.
17/246,466 (claims 83 and 104; claims filed 9th, March, 2026). A notice of allowance as mailed on 23rd, March, 2026. When the Patent issues this rejection will no longer be provisional.
17/265,910 (claims 1, 17, 22, 42, 48, 64-65; claims filed 26th, March, 2026). A notice of allowance as mailed on 26th, May, 2026. When the Patent issues this rejection will no longer be provisional.
16/623,799 (claim 1; claims filed 17th, April, 2026). A notice of allowance as mailed on 28th, April, 2026. When the Patent issues this rejection will no longer be provisional.
18/109,550 (claim 31; claims filed 21st, July, 2025)
16/938,110 (claim 60; claims filed 8th, July, 2025)
16/906,580 (claim 30; claims filed 8th, July, 2025)
16/535,043 (claims 47 and 63; claims filed 4th, May, 2023)
15/967,495 (claims 61-63; claims filed 30th, June, 2021)
15/230,025 (claim 1; claims filed 31st, March, 2020)
15/230,161 (claims 10-11; claims filed 10th, December, 2021)
15/160,710 (claim 1; claims filed 27th, January, 2021)
Applications which list Soumya Kannan as an Inventor:
16/617,560 (claim 1; claims filed 26th, March, 2026) (also lists Zhang as inventor above)
17/638,355 (claims 1, 15, 20-21; claims filed 13th, February, 2026) (also lists Zhang as inventor above)
19/016,260 (claims 1, 14, 20-22; claims filed 31st, March, 2025) (also lists Zhang as inventor above)
19/388,533 (claims 1, 21-22, 24, 28, 30, 34, 71, 75, 83, 86, 105, 127, 137, 140; claims filed 5th, January, 2026) (also lists Zhang as inventor above)
19/563,393 (claims 1 and 8; claims filed 28th, April, 2026) (also lists Zhang as inventor above)
18/965,935 (claims 1 and 4-17; claims filed 26th, March, 2026) (also lists Zhang as inventor above)
17/264,340 (claims 4, 8 and 17; claims filed 21st, April, 2026) (also lists Zhang as inventor above)
17/776,269 (claims 1, 48, 56; claims filed 9th, January, 2026) (also lists Zhang as inventor above)
17/793,115 (claims 1, 33, 40 and 43; claims filed 24th, February, 2026) (also lists Zhang as inventor above)
17/761,292 (claims 1, 24, 27, 31, 42, 44-45, 48; claims filed 1st, May, 2026) (also lists Zhang as inventor above)
17/801,815 (claims 1-2, 18 and 60; claims filed 6th, April, 2026) (also lists Zhang as inventor above)
16/623,799 (claim 1; claims filed 17th, April, 2026). A notice of allowance as mailed on 28th, April, 2026. When the Patent issues this rejection will no longer be provisional. (also lists Zhang as inventor above)
Applications which list Han Altae-Tran as an Inventor:
17/638,355 (claims 1, 15, 20-21; claims filed 13th, February, 2026) (also lists Zhang and Kannan as inventors above)
19/016,260 (claims 1, 14, 20-22; claims filed 31st, March, 2025) (also lists Zhang and Kannan as inventors above)
19/388,533 (claims 1, 21-22, 24, 28, 30, 34, 71, 75, 83, 86, 105, 127, 137, 140; claims filed 5th, January, 2026) (also lists Zhang and Kannan as inventors above)
19/563,393 (claims 1 and 8; claims filed 28th, April, 2026) (also lists Zhang and Kannan as inventors above)
17/612,504 (claims 1 and 41-44; note that claim 1 also specifically meets instant claim 8 because the cas protein is between 600-750 amino acids in size; claims filed 2nd, January, 2026) (also lists Zhang as inventor above)
18/965,935 (claims 1 and 4-17; claims filed 26th, March, 2026) (also lists Zhang and Kannan as inventors above)
17/776,269 (claims 1, 48, 56; claims filed 9th, January, 2026) (also lists Zhang and Kannan as inventors above)
17/793,115 (claims 1, 33, 40 and 43; claims filed 24th, February, 2026) (also lists Zhang and Kannan as inventors above)
17/761,292 (claims 1, 24, 27, 31, 42, 44-45, 48; claims filed 1st, May, 2026) (also lists Zhang and Kannan as inventors above)
17/785,070 (claims 7-11; claims filed 4th, May, 2026) (also lists Zhang as inventor above)
17/801,815 (claims 1-2, 18 and 60; claims filed 6th, April, 2026) (also lists Zhang and Kannan as inventors above)
Although the claims in the cited co-pending Applications above are not identical, they are not patentably distinct for the reasons stated below.
Claims 1-3, 7 and 17 are rejected on the ground of nonstatutory double patenting as being unpatentable over the cited claims of the co-pending Applications listed above, as evidenced by Nishimasu et al. (Cell. 2014 Feb 13;156(5):935–949.; henceforth “Nishimasu”) and NCBI Reference Sequence: WP_033888930.1 (accessed at: https://www.ncbi.nlm.nih.gov/protein/WP_033888930.1?report=genbank&log$=protalign&blast_rank=15&RID=2JWM2JTA014) because they claim a composition comprising a Cas protein or Cas effector protein in the identified claims that meets the structural requirements of instant claims or make obvious the instant claims.
Regarding claim 1, the claim requires the structure of a Cas protein, wherein the Cas protein comprises an N-terminal X domain, a RuvC domain, and a Bridge Helix domain. As set forth above, all possible N terminal domains of the Cas meet the limitation of an N-Terminal X domain because they are “a polypeptide domain on the N-terminal side that has a structural similarity and/or sequence similarity to an n-terminal domain described in the art” as set forth in the claim interpretation above. As set forth above, Cas proteins comprise a RuvC domain, and a Bridge Helix domain.
Regarding claim 1, the preamble of “engineered, non-naturally occurring,” this recites product-by process language (see MPEP 2113). Cas proteins or effector proteins meets the structural limitations of instant claims for the reasons set forth above, and therefore meet instant claims.
Instant claim 2 requires the Cas protein further comprises a C-terminal Y domain and/or an HNH domain. HNH domains are inherently comprised by Cas proteins or effector proteins and all possible C-terminal domains meet the limitations of a C Terminal Y-domain because they structural similarity and/or sequence similarity to a C-terminal domain described in the art, as set forth in the claim interpretation above.
Regarding claim 3, as set forth above, the Cas proteins evidenced by Nishimasu et al. (Cell. 2014 Feb 13;156(5):935–949.; henceforth “Nishimasu”), meets the structural limitations of instant claim because the N-terminal X domain, which is met by the structure of the N terminal domains of the Cas9 includes the option of the RUVC1 domain which is 60 amino acids long and is therefore no more than 70 amino acids long.
Therefore, instant claims 1-3, as presently claimed, presents a non-statutory double patenting issue with any claim that is drawn to a composition that comprises a Cas, Cas9 or effector protein.
Regarding claim 7, as set forth above, instant SEQ ID NO: 11 is 100% identical to the sequence of Cas9, as evidenced by NCBI Reference Sequence: WP_033888930.1.
Regarding claim 17, as stated above, a PAM of NGG is an inherent property of Cas9.
Therefore, instant claims 7 and 17 presents a non-statutory double patenting issue with any claim that comprises or encompasses a Cas9 protein.
Therefore, because the instant Application claims are anticipated by or obvious over the cited Application claims, as evidenced by Nishimasu and WP_033888930.1., said claims are not patentably distinct.
Claim 8 is rejected on the ground of nonstatutory double patenting as being unpatentable over the cited claims of the co-pending Applications listed above, as evidenced by Nishimasu et al. (Cell. 2014 Feb 13;156(5):935–949.; henceforth “Nishimasu”) and NCBI Reference Sequence: WP_033888930.1 (accessed at: https://www.ncbi.nlm.nih.gov/protein/WP_033888930.1?report=genbank&log$=protalign&blast_rank=15&RID=2JWM2JTA014) and further evidenced by Harrington et al. (Science. 2018 Nov 16;362(6416):839-842. Epub 2018 Oct 18.), because they claim a composition comprising a Cas protein or Cas effector protein in the identified claims that meets the structural requirements of instant claims or make obvious the instant claims.
The teachings of the cited co-pending Applications above, Nishimasu, and WP_033888930.1 are incorporated herein in their entirety.
Regarding claim 8, as set forth above, Cas14 (also known as Cas12f) meets the structural requirements of instant claims because it is a small Cas protein of 400-700 amino acids in length Harrington evidence Cas14, also known as Cas12f, which is a naturally occurring, small Cas protein that is 400-700 aa length (Harrington pg. 1 col. 1).
Therefore, instant claim 8 presents a non-statutory double patenting issue with a claim drawn to a composition that comprises a Cas14 or Cas12f protein, or otherwise meets the length requirements of the claim.
Additionally, regarding claim 8, the N-terminal X domain can be of any length and Nishimasu evidences RuvC domains of RuvC1 of 60 amino acids, and BH domain of 34 amino acids, which requires a length of 93 amino acids and some length of N-terminal X domain. Therefore, Cas proteins and effector protein claims that also encompass these elements encompass embodiments of instant claims that are less than 500, 600, 700, or 800 amino acids.
Claims 12 and 24 are rejected on the ground of nonstatutory double patenting as being unpatentable over the cited claims of the co-pending Applications listed above, as evidenced by Nishimasu et al. (Cell. 2014 Feb 13;156(5):935–949.; henceforth “Nishimasu”) and NCBI Reference Sequence: WP_033888930.1 (accessed at: https://www.ncbi.nlm.nih.gov/protein/WP_033888930.1?report=genbank&log$=protalign&blast_rank=15&RID=2JWM2JTA014) as applied to claim 1 above, and in further view of Maianti et al. (WO-2018/165631-A1; henceforth “Maianti”) because they claim a composition comprising a Cas protein or Cas effector protein in the identified claims that meets the structural requirements of instant claims or make obvious the instant claims.
The teachings of the cited co-pending Applications above, Nishimasu, and WP_033888930.1 are incorporated herein in their entirety.
Regarding claims 12 and 24, Maianti teaches compositions where the domains of the Cas protein are catalytically inactive (“dCas9” para. [0128]; see also para. [0007-0008, 0129-0130, 0135, 0205-0208, 0235, 0245, 0247, 0254, 0259, 0307]) (instant claim 12), Maianti teaches nucleotide deaminase associated with or otherwise capable of forming a complex with the Cas protein wherein the nucleotide deaminase is a cytidine deaminase (“cytosine deaminase” abstract; see also para. [0004-0005, 0010-0012, 0061, 0069-0072, 0131-0134, 0137, 0145, 0171, 0204, 0230, 0237-0247, 0254-0257, 0259-0260, 0306, 0312, 0326]; claims 1, 14-16, 18, 20, 22-24, 186, 193-194, 205-207) (instant claims 12 and 24), and Maianti teaches a single guide molecule capable of forming a complex with the Cas protein and directing site-specific binding at a target sequence (para. [0118, 0129, 0210, 0265-0267]) (instant claim 24). It would be obvious to combine these known prior art elements because Maianti teaches including these to edit selected target sites by nucleobase editors (abstract) and to introduce targeted mutations into tumor-specific antigens (para. [0004]), and also provides a reasonable expectation of success in preparing such a composition (Examples 1-2).
Therefore, in view of Maianti, instant claims 12 and 24 are obvious.
Claim 16 is rejected on the ground of nonstatutory double patenting as being unpatentable over the cited claims of the co-pending Applications listed above, as evidenced by Nishimasu et al. (Cell. 2014 Feb 13;156(5):935–949.; henceforth “Nishimasu”) and NCBI Reference Sequence: WP_033888930.1 (accessed at: https://www.ncbi.nlm.nih.gov/protein/WP_033888930.1?report=genbank&log$=protalign&blast_rank=15&RID=2JWM2JTA014) as applied to claim 1 above, and in further view of Jaskula-Ranga et al. (WO-2018009534-A1; henceforth “Jaskula-Ranga”) because they claim a composition comprising a Cas protein or Cas effector protein in the identified claims that meets the structural requirements of instant claims or make obvious the instant claims.
The teachings of the cited co-pending Applications above, Nishimasu, and WP_033888930.1 are incorporated herein in their entirety.
Regarding claim 16, Jaskula-Ranga teaches a composition with a Cas protein and a homologous recombination donor template comprising a donor sequence for insertion into a target polynucleotide (abstract; pg. 4, 10-11, 21, 31, 61, 139, 172). It would be obvious to combine these known prior art elements because Jaskula-Ranga teaches including the donor template for correcting mutations (abstract), and also provides a reasonable expectation of success in preparing such a composition (Examples 1-3).
Therefore, in view of Jaskula-Ranga, instant claims 16 is obvious.
Examiner’s Remark
The instant claims conflict with the specifically identified claims of the many U.S. Co-pending Applications above. Pursuant to 37 CFR 1.78(f), when two or more applications filed by the same applicant or assignee contain patentably indistinct claims, elimination of such claims from all but one application may be required in the absence of good and sufficient reason for their retention during pendency in more than one application. Applicant is required to either cancel the patentably indistinct claims from all but one application or maintain a clear line of demarcation between the applications. See MPEP § 822.
Conclusion
No claim is allowable.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRIANA N EBBINGHAUS whose telephone number is (703)756-4548. The examiner can normally be reached M-F 9:30 AM to 5:30 PM ET.
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/BRIANA N EBBINGHAUS/Examiner, Art Unit 1632 /VALARIE E BERTOGLIO/Primary Examiner, Art Unit 1632
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