DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s Response to Election/Restriction Filed, Amendment, and Arguments/Remarks, filed 19 August 2025, have been entered. Claims 1-2, 5-6, 9, 11-13, 15, 17-19, 22-26, 28, 30-31, 33-38, 40, 42-50, and 60 are currently pending in the application. Claims 1, 18, 23, 24, 25, 34, 37, and 38 are independent claims. Applicant’s election of the invention of Group I, claims 1-2, 5-6, 9, 11-13, 15, 17-19, 22-24, 34-37, 40, 42-50, and 60, drawn to a first non-naturally occurring, engineered composition; an engineered cell comprising the composition; a first composition comprising one or more polynucleotides; a vector comprising the one or more polynucleotides; a second non-naturally occurring, engineered composition, and a second composition comprising one or more polynucleotides, is acknowledged.
Additionally, Applicant’s election of the following species:
Cas systems/proteins types: a. Class I, Type IV Cas systems/proteins: i. SEQ ID NO: 458;
Cells: b.i. mammalian cell;
PAM sequences: a. CC;
in a reply filed 19 August 2025 is acknowledged.
Applicant has not indicated whether the election of Group I nor the election of species was made with or without traverse. However, Applicant argues that Applicant does not agree with the characterization of Barangou as a reference for breaking unity of invention, but does not distinctly and specifically point out the supposed errors in the restriction requirement, and so the election has been treated as an election without traverse (MPEP § 818.01(a)). Additionally, Applicant has not provided any arguments traversing the election of species requirement(s). Therefore, the election of species SEQ ID NO: 458, mammalian cell, and PAM sequence “CC” are also considered to have been made without traverse. Note that cells types are only recited in the nonelected Group II, and as such the election of mammalian cell is moot for consideration of the invention of Group I.
Claims 25-26, 28, 30-31, 33, and 38 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 40, 42-50, and 60 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Claims 1-2, 5-6, 9, 11-13, 15, 17-19, 22-24, and 34-37 are currently pending in the application and under examination to which the following grounds of rejection are applicable. An action on the merits follows.
Priority
The present application is a 35 U.S.C. 371 national stage filing of International Application No. PCT/US2021/019494, filed 24 February 2021, which claims priority to U.S. Provisional Application Nos. 62/980,904, filed 24 February 2020, 62/980,922, filed 24 February 2020, and 63/000,224, filed 26 March 2020.
Thus, the earliest possible priority for the instant application is 24 February 2020.
Information Disclosure Statement
The information disclosure statements filed 24 August 2022 and 18 April 2023 have been considered by the Examiner.
37 CFR 1.821-1.825
This application contains sequence disclosures that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.821(a)(1) and (a)(2), see for example specification paragraphs [00164-00165, 00840], Table 1 (e.g., Csf2 (Cas7 like), 5rd row), and Figures 2 and 4. However, this application fails to comply with the requirements of 37 CFR 1.821 through 1.825 for the reason(s) set forth below and on the Notice to Comply With Requirements For Patent Applications Containing Nucleotide Sequence And/Or Amino Acid Sequence Disclosures which is attached to this communication.
Specifically, specification paragraphs [00164-00165, 00840], Table 1 (e.g., Csf2 (Cas7 like), 5rd row), and Figures 2 and 4 disclose amino acid and/or nucleotide sequences but do not include some of the sequence identifiers. Note that MPEP 2422.01(V) recites, 37 CFR 1.821(d) further requires that where the description or claims of a patent application discuss a sequence that is set forth in the "Sequence Listing", a reference to the sequence identifier of that sequence is required at all occurrences, even if in the text of the description or claims where the sequence is set forth by enumeration of its residues” (emphasis added). A sequence identifier must be included each time the sequence is recited.
If the unidentified sequences of specification paragraphs [00164-00165, 00840], Table 1 (e.g., Csf2 (Cas7 like), 5rd row), and Figures 2 and 4 are included in the submitted sequence listing, Applicant must amend the claims and specification and/or drawings to comply with the sequence identification requirements. Alternatively, if the unidentified sequences of specification paragraphs [00164-00165, 00840], Table 1 (e.g., Csf2 (Cas7 like), 5rd row), and Figures 2 and 4 are not included in the presently submitted sequence listing, Applicant must submit an updated sequence listing in compliance with 37 CFR 1.821(c)-(d) and 37 CFR 1.825(b). See also the attached Notice to Comply.
APPLICANT IS GIVEN A THREE MONTH EXTENDABLE PERIOD WITHIN WHICH TO COMPLY WITH THE SEQUENCE RULES, 37 CFR 1.821-1.825. Failure to comply with these requirements will result in ABANDONMENT of this application under 37 CFR 1.821 (g). Extension of time may be obtained by filing a petition accompanied by the extension fee under the provisions of 37 CFR 1.136. In no case may an applicant extend the period for response beyond the six month statutory period. Applicant is requested to return a copy of the attached Notice to Comply with the response.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, including into the Brief Description of the Drawings, 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.
Claim Objections
Claims 1-2, 18, 22, 34, and 35 are objected to because of the following informalities: claim 1 recites the abbreviations “DinG” and “HNH”; claim 2 recites the abbreviations ”Cse3”, ”Csf2”, “Csf3”, and “Pfam08798”; claim 18 recites the abbreviation “DinG”; claim 22 recites the abbreviations ”Csf2”, “Csf3”, and “Pfam08798”; claim 34 recites the abbreviation “HNH”; and claim 35 recites the abbreviation “DinG” without first writing out the terms for which the abbreviations stand.
Claim 18 additionally recites, “Cas5 protein with a length less than”, wherein the text is underlined. Claim 18 also indicates that the claim is “(Previously Presented)”. The underlined text seems to indicate an insertion, and therefore an amendment to the claim. However, the underlined text was included in the prior version of the claim.
Appropriate correction is required.
Claim 5 is objected to because of the following informalities: Claim 5 recites, “sequence listed in Table 1”. Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table “is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience.” Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted). See MPEP 2173.05(s). Appropriate correction is required.
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 1-2, 5-6, 9, 11-13, 15, 17-19, and 22-24 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. Claims 23 and 24 are included in this rejection due to their dependence on/ encompassing of claims 1 and/or 18.
Independent claim 1 has multiple issues of indefiniteness.
Independent claim 1 recites, “a Class 1, Type IV Cas system comprising a helicase comprising a DinG domain and a HNH domain that is less than 600 amino acids in length” in lines 2-3, which is indefinite because it is unclear which of the Cas system, the helicase, or the HNH domain is meant to be less than 600 amino acids in length.
Claim 1 additionally recites, “a Class I, Type I Cas system comprising an HNH domain that is less than 400 amino acids in length” in lines 6-7, which is indefinite because it is unclear whether the system or the HNH domain are meant to be less than 400 amino acids in length.
Claim 1 also recites, “the Cas system” in lines 7-8. There is insufficient antecedent basis for this limitation in the claim. Claim 1 recites both “a Class 1, Type IV Cas system” in line 2 and “a Class I, Type I Cas system” in line 6, and so it is unclear which Cas system is being referred to in lines 7-8.
Claim 1 recites, “the guide-Cas system complex” in lines 4-5 and again in line 8. There is insufficient antecedent basis for this limitation in the claim. Claim 1 recites “at least one guide sequence capable of complexing with the Cas system” both in lines 3-4 and 7-8, but does not have any prior recitations of a guide-Cas system complex. Additionally, to the extent that “the guide-Cas system complex” is meant to refer to the complex formed by the “at least one guide sequence capable of complexing with the Cas system” and the Cas system with which is it capable of complexing, it is unclear which at least one guide sequence and which Cas system are making up the guide-Cas system complex of lines 7-8.
Claim 1 also recites, “at least one guide sequence” in lines 3 and 6, which is indefinite because it is unclear how a composition can comprise a sequence in that a sequence is just information without substance.
As such, the metes and bounds of the claim cannot be determined.
Regarding claims 2, 6, 9, 13, and 19 the term "preferably" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). As such, the metes and bounds of the claim cannot be determined.
Claim 5 recites, “the Class I, Type IV Cas system Cas protein” in lines 1-2. There is insufficient antecedent basis for this limitation in the claim. Claim 5 is dependent on claim 1. Neither claims 5 nor claim 1 have any prior recitation of a Class I, Type IV Cas system Cas protein. Additionally, it is unclear whether the Cas protein of claim 5 is meant to be the helicase comprising a DinG domain and a HNH domain recited in claim 1 or whether the Cas protein recited in claim 5 is meant to be an additional Cas protein of the Class I, Type IV Cas system.
Claim 5 further recites, “a protein with nucleotide sequence”, which is indefinite because it is unclear in what way a protein is “with” a nucleotide sequence. For example, it is unclear whether Applicant intends to claim a protein which is encoded by a recited nucleotide sequence or whether Applicant intends to recite a nucleotide sequence in addition to the protein.
Additionally, if the former, recitation of “the Class 1, Type IV Cas system Cas protein is a protein with nucleotide sequence listed in Table 1 and SEQ ID NOs 1-405” is further indefinite in that it is unclear whether the Cas protein must have the full sequence of the protein sequences encoded by the recited nucleotide sequence or whether it may comprise any portion of a protein encoded by the recited sequences.
The claim is even further indefinite in that it is unclear whether the Cas protein is meant to be encoded by/ present with all of the nucleotides sequences listed in Table 1 and SEQ ID NOs 1-405 or whether the Cas protein is meant to be encoded by/ present with any one (or more) of the nucleotides sequences listed in Table 1 and SEQ ID NOs 1-405.
Additionally, if the Cas protein recited in claim 5 is meant to be the helicase comprising a DinG domain and a HNH domain recited in claim 1, the claim is further indefinite in that not all sequences recited comprise both a DinG domain and an HNH domain.
As such, the metes and bounds of the claim cannot be determined.
Claims 6 and 9 additionally recite, “the Class I, Type IV Cas system Cas target sequence” in lines 1-2 of each claim. There is insufficient antecedent basis for this limitation in the claim. Neither claim 1, upon which claims 6 and 9 depends nor either claim 6 or 9 have any prior recitation of a Class I, Type IV Cas system Cas target sequence.
Claims 6 and 9 further recite, “target sequence comprises a protospacer adjacent motif (PAM) at the 5’ side of the target sequence” (claim 6) and ““target sequence comprises PAM at the 3’ side of the target sequence” (claim 9), which is indefinite because it is unclear whether the PAM is comprised within the target sequence or whether the PAM is to the side of the target sequence.
As such, the metes and bounds of the claim cannot be determined.
Claim 11 recites, “cascade/helicase” activity, which is indefinite because it is unclear whether the “/” between terms is meant to indicate that the terms are synonyms of each other or whether it is meant to indicate alternative options. As such, the metes and bounds of the claim cannot be determined.
Claims 11 and 12 each recite, “the Class 1, Type IV Cas system composition” in lines 1-2. There is insufficient antecedent basis for this limitation in the claims. None of claims 11, 12, nor 1 (upon which claims 11 and 12 depend) have any prior recitation of a Class 1, Type IV Cas system composition. As such, the metes and bounds of the claim cannot be determined.
Claims 13 and 15 recite, “the target polynucleotide” in lines 3 and 4 (claim 13) and lines 4-5 (claim 15). There is insufficient antecedent basis for this limitation in the claim. Claim 15 depends on claim 13; claim 13 depends on claim 1; claim 1 recites “a target polynucleotide” in both lines 5 and 8-9. As such, the metes and bounds of the claim cannot be determined.
Claim 17 recites, “the Cas protein” and “the guide-Cas protein complex” in lines 2 and 2-3, respectively. There is insufficient antecedent basis for this limitation in the claim. Claim 17 is dependent on claim 1. Neither claim 1 nor claim 17 have any prior recitation of a Cas protein or a guide-Cas protein complex. As such, the metes and bounds of the claim cannot be determined.
Independent claim 18 recites, “the guide-Cas protein complex” in lines 5 and 10. There is insufficient antecedent basis for this limitation in the claim. Claim 18 has no prior recitation of a guide-Cas protein complex. As such, the metes and bounds of the claim cannot be determined.
Claim 22 recites, “Csf2 (Cas7-like)”, “Csf3 (Cas5-like)”, and “Pfam08798 (Cse3 family)”, which are indefinite because it is unclear if the parenthetical terms are meant to further limit the preceding terms or whether they are meant to be exemplary of the preceding terms. As such, the metes and bounds of the claim cannot be determined.
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, 5-6, 9, 11-12, 17-18, 22-24, and 34-37 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a product of nature without significantly more. Independent claim 1 as elected recites a Class I, Type IV Cas system comprising a helicase comprising a DinG domain and an HNH domain, at least one guide sequence capable of complexing with the Cas system and directing binding of the guide-Cas system complex to a target polynucleotide. The elected sequence of Cas protein is a Cas protein encoded by instant SEQ ID NO: 458 (recited in claim 5). SEQ ID NO: 458 encodes a 534 amino acid protein which is a naturally occurring HNH endonuclease from Sulfuritalea sp. (MAG: HNH endonuclease) [GenBank 2022, GenBank: MCK9382108.1, MAG: HNH endonuclease [Sulfuritalea sp.], retrieved on 19 November 2025 from: <https://www.ncbi.nlm.nih.gov/protein/MCK9382108.1?report=genbank&log$=protalign&blast_rank=1&RID=HWC347YU014>]. InterPro teaches that the sequence encoded by the nucleotide sequence of instant SEQ ID NO: 458 comprises a DEAD box helicase domain [InterPro 2025, InterPro Classification of protein families, InterProScan Search Result, retrieved on 25 November 2025 from: https://www.ebi.ac.uk/interpro/result/InterProScan/iprscan5-R20251125-195917-0249-38824601-p1m/internal-1764100748930-79-1/, page 1 entry matches, page 2 entry 4]. Further, Makarova teaches that the presence of a dinG gene encoding a DinG helicase is diagnostic for a class I subtype IV Cas system [Makarova et al. 2018, The CRISPR Journal, 1(5), 325-336, column 4 ¶ 4, Figure 1]. Makarova also teaches that the Type IV Cas systems have effector modules and CRISPR arrays [Figure 1]. Crowley teaches that prokaryotes use small non-coding RNAs derived from CRISPR arrays to guide Cas proteins to invasive complementary nucleic acids such as phage and plasmid DNA for destruction [Crowley et al. [2019, The CRISPR Journal, 2(6), 434-440, column 1 ¶ 1]. Therefore, independent claim 1 encompasses a naturally occurring Class I, Type IV Cas system.
Dependent claim 2 recites additional components of the system which encompass naturally occurring components of a Type IV Cas system [Crowley Figure 1, Makarova Figure 1]. Dependent claims 5, 9, 11-12, and 17 recite additional natural functions or features of the above described naturally occurring Type IV Cas systems. Claim 24 encompassing a natural Sulfuritalea sp. comprising the native Cas system, as described above.
Independent claim 18 as elected is directed to one or more polynucleotides encoding one or more class 1, Type IV Cas proteins or functional fragments thereof, wherein the one or more class 1, Type IV Cas proteins comprises a DinG protein with a length less than 600 amino acids; and one or more guide molecules capable of complexing with the class I, Type IV Cas protein and directing binding of the guide-Cas protein complex to one or more target polynucleotides. Independent claim 18 is thus a genus of independent claim 1 and encompasses a naturally occurring Class I, Type IV Cas system.
Dependent claim 22 recites additional components of the system which encompass naturally occurring components of a Type IV Cas system [Crowley Figure 1, Makarova Figure 1]. CRISPRone teaches that pfam08798 is Cas6e and is encoded by a gene immediately upstream of a gene encoding a type IV-A DinG Cas protein [CRISPRone 2018, CRISPRone report for GCA_900502815.1_18623_2_89, retrieved on 25 November 2025 from: https://omics.informatics.indiana.edu/CRISPRone/check.php?id=GCA_900502815.1_18623_2_89&col=refined>, updated 01 August 2018, page 2 lines 1-5]. Additionally, Taylor teaches that Type IV-A Cas systems contain a dinG helicase gene, a cas6 endonuclease gene, csf2, csf3, cas6, and a cas6e gene [Taylor et al. 2019, RNA Biology, 16(10), 1438-1447, column 2 ¶ 2, Figure 1]. Therefore, claim 22 encompasses a naturally occurring Class I, Type IV Cas system.
Independent claim 34 as elected recites a Cas protein that comprises an HNH domain and a helicase domain, and at least one guide sequence capable of complexing with the Cas protein and directing binding of the guide-Cas protein complex to a target polynucleotide, which as elected encompasses the naturally occurring HNH endonuclease-helicase from Sulfuritalea sp. and guide RNAs as described above for independent claim 1. As such, claim 34 also encompasses a naturally occurring Class I, Type IV Cas system.
Dependent claims 35-37 recite additional limitations as described above for claims 1 and 18, and as such also encompasses a naturally occurring Class I, Type IV Cas system.
This judicial exception is not integrated into a practical application because the claims merely recite the compositions and do not recite any additional elements or limitations which would integrate the composition into a practical application. The claims merely recite that the composition is “non-naturally occurring, engineered” (claim 1), “engineered” (claim 24), or “non-naturally occurring” (claim 34), which does not add a meaningful limitation as it is merely a nominal or token extra-solution component of the claim, and is nothing more than an attempt to generally link the product of nature to a particular technological environment. None of the limitations within the claim require any non-natural or engineered features.
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because no additional elements are recited.
Therefore, the product(s) of nature as recited are not accompanied by additional elements which integrate them into a practical application or amount to significantly more than the judicial exception.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-2, 5-6, 9, 11-13, 15, 17-19, 22-24, and 34-37 are rejected under 35 U.S.C. 103 as being unpatentable over Hou [US20190264232A1, published 29 August 2019]; in view of GenBank [2022, GenBank: MCK9382108.1, MAG: HNH endonuclease [Sulfuritalea sp.], retrieved on 19 November 2025 from: <https://www.ncbi.nlm.nih.gov/protein/MCK9382108.1?report=genbank&log$=protalign&blast_rank=1&RID=HWC347YU014>]; InterPro [2025, InterPro Classification of protein families, InterProScan Search Result, retrieved on 25 November 2025 from: <https://www.ebi.ac.uk/interpro/result/InterProScan/iprscan5-R20251125-195917-0249-38824601-p1m/internal-1764100748930-79-1/>]; Makarova et al. [2018, The CRISPR Journal, 1(5), 325-336]; Crowley et al. [2019, The CRISPR Journal, 2(6), 434-440]; CRISPRone [2018, CRISPRone report for GCA_900502815.1_18623_2_89, retrieved on 25 November 2025 from: https://omics.informatics.indiana.edu/CRISPRone/check.php?id=GCA_900502815.1_18623_2_89&col=refined>, updated 01 August 2018]; and Taylor et al. [2019, RNA Biology, 16(10), 1438-1447].
Note that claim 5 recites, “a protein with nucleotide sequence listed in Table 1 and SEQ ID NOs 1-405”, which has been interpreted to encompass proteins encoded by the nucleotide sequences presented in Table 1 of the specification (e.g., SEQ ID NOs: 455-493) or encoded by the nucleotide sequences according to SEQ ID NOs: 1-405.
Note additionally that claims 2, 5, 6, 9, and 11-12 further limit an option (a) of claim 1 without requiring selection of that option. Additionally, claim 15 further limits an optional (preferable) limitation of claim 13 without requiring incorporation of that (preferable) option. Claim 22 further limits and option of claim 18 without requiring selection of that option.
Regarding claims 1 and 5, Hou teaches a synthetic composition comprising a Cas system comprising a polypeptide encoded by a gene encoding a Cas endonuclease identified, derived, or isolated from an organism selected from a group consisting of a list which includes Sulfuritalea hydrogenivorans [0007-0008]. Hou also teaches that the composition comprises guide polynucleotides capable of forming a complex with a Cas endonuclease to recognize and bind to a target polynucleotide [0010, 0237].
Hou does not teach that a Cas endonuclease from Sulfuritalea hydrogenivorans is a class I, Type IV Cas system helicase comprising a DinG domain and an HNH domain that is less than 600 amino acids in length, nor that the Cas endonuclease from Sulfuritalea hydrogenivorans is a protein encoded by the nucleotide sequence according to instant SEQ ID NO: 458 (the elected species of Class I, Type IV Cas system Cas protein, which the instant specification teaches encodes a DinG helicase [Table 1]).
However, GenBank teaches an HNH endonuclease from Sulfuritalea sp. (MAG: HNH endonuclease) which has 100% identity to the full-length amino acid sequence (534 amino acids) encoded by instant SEQ ID NO: 458 and comprises an HNH endonuclease domain [page 1 title, page 2 lines 14-15, 23, 26-35]:
PNG
media_image1.png
531
675
media_image1.png
Greyscale
InterPro teaches that the sequence encoded by the nucleotide sequence of instant SEQ ID NO: 458 additionally comprises a DEAD box helicase domain [page 1 entry matches, page 2 entry 4]. Further, Makarova teaches that the presence of a dinG gene encoding a DinG helicase is diagnostic for a class I subtype IV Cas system [column 4 ¶ 4, Figure 1].
Therefore, by teaching to select a Cas endonuclease from Sulfuritalea hydrogenivorans, Hou is teaching to select a Class I, Type IV Cas system protein which encompasses the MAG: HNH endonuclease taught by GenBank which has less than 600 amino acids in length. Additionally, given that protein domain structures are inherent properties of the amino acid sequence of the protein, the MAG: HNH endonuclease taught by Hou in view of GenBank is a teaching of a helicase comprising a DEAD/DEAH-box helicase domain/DinG helicase domain and an HNH domain.
Reliance upon inherency is not improper even though rejection is based on Section 103 instead of Section 102. In re Skoner, et al. 186 USPQ 80 (CCPA). As stated in MPEP 2112, The express, implicit, and inherent disclosures of a prior art reference may be relied upon in the rejection of claims under 35 U.S.C. 102 or 103. "The inherent teaching of a prior art reference, a question of fact, arises both in the context of anticipation and obviousness." In re Napier, 55 F.3d 610, 613, 34 USPQ2d 1782, 1784 (Fed. Cir. 1995). See also In re Grasselli, 713 F.2d 731,739, 218 USPQ 769, 775 (Fed. Cir. 1983). There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003).
Given the teachings of Hou to include a Cas endonuclease from Sulfuritalea hydrogenivorans in a composition comprising a Cas endonuclease and a guide nucleic acid, wherein the guide nucleic acid complexes with the Cas endonuclease and directs binding of the guide-Cas system complex to a target polynucleotide, it would have been prima facie obvious to an ordinarily skilled artisan at the time of filing the instant application to select one of the Cas endonucleases taught by Hou, such as the Cas endonuclease-helicase from Sulfuritalea hydrogenivorans encoded by instant SEQ ID No: 458, with a reasonable expectation of success.
Regarding dependent claim 2, Hou, GenBank, InterPro, and Makarova teach the limitations of claim 1. Hou additionally teaches that the Cas system comprises additional Cas proteins, such that a characteristic feature of the Class I, Type IV systems is the presence of an effector endonuclease complex instead of a single protein [0181-0183]. Makarova further teaches that Type IA systems comprise dinG, cas6-like, cas8-like, cas7, and cas5 genes [Figure 1].
Regarding claims 6 and 9, Hou teaches wherein the target sequence comprising a protospacer adjacent motif (PAM) at the 5’ side of the gRNA target sequence or at the 3’ side of the gRNA target sequence [Figure 15, 19]. Hou also teaches wherein the PAM sequence comprises CC (the elected species) [0009].
Regarding claim 11, Hou, GenBank, InterPro, and Makarova teach the limitations of claim 1, wherein the Sulfuritalea hydrogenivorans Cas protein encoded by instant SEQ ID NO: 458 (as elected) comprises a helicase domain.
Crowley teaches that DinG helicase proteins of Class 1, Type IV Cas systems have putative NTP-dependent helicase activity, which is required for type IV CRISPR-Cas system-mediated RNA-guided interference against plasmids in vivo [abstract, column 8 ¶ 2]. Therefore, the Sulfuritalea hydrogenivorans Cas protein encoded by instant SEQ ID NO: 458 (as elected) taught by Hou, GenBank, InterPro, and Makarova comprises helicase activity, and as such the Class 1, Type IV Cas system comprises helicase activity.
Regarding claim 12, Hou, GenBank, InterPro, and Makarova teach the limitations of claim 1. Hou teaches that Cas3 is a feature of Class 1, Type I systems [0187]. Makarova teaches that the Cas3 helicase is a part of type I systems [column 3 ¶ 1, column 4 ¶ 3]. Makarova further teaches that Type IA systems comprise dinG, cas6-like, cas8-like, cas7, and cas5 genes, but not cas3 [Figure 1]. Therefore, the Class 1, Type IV Cas system taught by Hou, GenBank, InterPro, and Makarova does not comprise Cas3 DNA shredding activity.
Regarding claims 13 and 15, Hou teaches that the composition comprises a donor DNA or a repair template polynucleotide, wherein the donor DNA introduces an insertion into the target site [0012, 0114, 0159, 0256, 0308, 0369].
Regarding claim 17, Hou teaches a composition comprising a plurality of guide molecules capable of complexing with the Cas endonuclease and directing binding of the guide-Cas endonuclease complex to one or more target polynucleotides [0239-0241].
Regarding claim 18, Hou teaches a composition comprising polynucleotides encoding the Class I, Type IV Cas protein and guide RNAs as described above [0002, 0007-0009, 0012, 0182].
Regarding claim 19, Hou teaches the composition comprises a donor polynucleotide [0012, 0114, 0159, 0256, 0308, 0369].
Regarding claim 22, Hou, GenBank, InterPro, and Makarova teach the limitations of claim 1. As discussed above, Hou additionally teaches that the Cas system comprises additional Cas proteins, such that a characteristic feature of the Class I, Type IV systems is the presence of an effector endonuclease complex instead of a single protein [0181-0183]. Makarova further teaches that Type IA systems comprise dinG, cas6-like, cas8-like, cas7, and cas5 genes [Figure 1]. Crowley teaches that Class 1, Type IV-A1, -A2, -A3, and -A4 Cas systems comprise Csf2, Csf3, and Csf5/Cas6 [Figure 1].
Hou, GenBank, InterPro, Makarova, and Crowley do not teach that the Class 1, Type IV Cas proteins comprise Pfam08798 (Cse3 family).
However, CRISPRone teaches that pfam08798 is Cas6e and is encoded by a gene immediately upstream of a gene encoding a type IV-A DinG Cas protein [page 2 lines 1-5]. Additionally, Taylor teaches that Type IV-A Cas systems contain a dinG helicase gene, a cas6 endonuclease gene, csf2, csf3, cas6, and a cas6e gene [column 2 ¶ 2, Figure 1].
Therefore, given the teachings of Taylor that natural Type IV Cas systems comprise dinG, csf2, csf3, cas6, and a cas6e genes encoding DinG, Csf2, CSf3, Cas6, and Cas6e proteins, it would be obvious to an ordinarily skilled artisan to include polynucleotides encoding Csf2, CSf3, Cas6, and Cas6e/Pfam08798 proteins in a composition comprising one or more class 1, Type IV Cas proteins comprising the DinG protein and a guide molecule according to claim 18, as taught by Hou, GenBank, InterPro, Makarova.
Regarding claim 23, Hou teaches a vector comprising the one or more polynucleotides as described above for claim 18 [0195, 0251, 0369].
Regarding claim 24, Hou teaches an engineered cell comprising the composition of claim 1 comprising the comprising the Class I, Type IV Cas system [0020-0025, 0084, 0127].
Regarding claims 34-37, as discussed above, Hou, GenBank, InterPro, and Makarova teach the limitations of claims 1 and 5, such that by teaching to select a Cas endonuclease from Sulfuritalea hydrogenivorans, Hou is teaching to select a Class I, Type IV Cas system protein which encompasses the MAG: HNH endonuclease taught by GenBank which has less than 600 amino acids in length. Additionally, given that protein domain structures are inherent properties of the amino acid sequence of the protein, the MAG: HNH endonuclease taught by Hou in view of GenBank is a teaching of a helicase comprising a DEAD/DEAH-box helicase domain/DinG helicase domain and an HNH domain.
Additionally, as discussed above, Hou teaches one or more polynucleotides encoding one or more components of the composition of claim 34 [0002, 0007-0009, 0012, 0182].
Given the teachings of Hou, GenBank, InterPro, Makarova, Crowley, CRISPRone, and Taylor that natural Class I, Type IV Cas systems comprise a DinG helicase (e.g., the DinG helicase of Sulfuritalea hydrogenivorans Cas protein encoded by instant SEQ ID NO: 458 which comprises a Ding domain and an HNH domain), along with Csf2, CSf3, Cas6, and Cas6e proteins, and polynucleotides which encode them; it would have been prima facie obvious to an ordinarily skilled artisan to modify the compositions of Hou to select the Sulfuritalea hydrogenivorans Cas DinG-HNH protein encoded by instant SEQ ID NO: 458 and to include the Sulfuritalea hydrogenivorans Cas DinG-HNH protein in a composition additionally comprising Csf2, CSf3, Cas6, and Cas6e proteins with a reasonable expectation of success.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Dr. KATIE L PENNINGTON whose telephone number is (703)756-4622. The examiner can normally be reached M-Th 8:30 am - 5:30 pm, Friday 8:30 am - 12:30 pm CT.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maria G. Leavitt can be reached on (571) 272-1085. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
DR. KATIE L. PENNINGTON
Examiner
Art Unit 1634
/KATIE L PENNINGTON/Examiner, Art Unit 1634
Dr. A.M.S. Wehbé
/ANNE MARIE S WEHBE/Primary Examiner, Art Unit 1634