DETAILED ACTION
Applicant’s amendment and Arguments/Remarks received on 06 April 2026 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 were previously pending in the application. Claim 5 has been cancelled by Applicant. Claims 1-2, 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.
The election 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, remains in effect in the instant application. The following election of species remains in effect in the instant application:
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.
Claims 25-26, 28, 30-31, 33, and 38 remain withdrawn from consideration as being directed to a nonelected invention, there being no allowable generic or linking claim.
Claims 40, 42-50, and 60 remain withdrawn from consideration as being directed to a nonelected species, there being no allowable generic or linking claim.
Claims 1-2, 6, 9, 11-13, 15, 17-19, 22-24, and 34-37 are currently pending and under examination in the instant application. An action on the merits follows.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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.
37 CFR 1.121(c)
The claim amendment filed 06 April 2026 is objected to under 37 CFR 1.121(c) because Applicant’s claim listing is not in compliance with 37 CFR 1.121(c) which states that the claim listing must provide the status of all claims, that all claims being currently amended in an amendment paper shall be presented in the claim listing, indicate a status of "currently amended," and be submitted with markings to indicate the changes that have been made relative to the immediate prior version of the claims, and that the text of all pending claims not being currently amended shall be presented in the claim listing in clean version, i.e., without any markings in the presentation of text. The presentation of a clean version of any claim having the status of "original," "withdrawn" or "previously presented" will constitute an assertion that it has not been changed relative to the immediate prior version, except to omit markings that may have been present in the immediate prior version of the claims of the status of "withdrawn" or "previously presented."
Specifically, claim 1 is marked “(Currently Amended)” and contains markings to indicate insertions and deletions from the previous version. However, some of the inserted text in amended claim 1 is not underlined, including the parentheses around “DinG” and “HNH”. Similarly, claim 2 is marked “(Currently Amended)” and contains markings to indicate insertions and deletions from the previous version. However, some of the inserted text in amended claim 2 is not underlined, including the parentheses around “Cse3”, “Csf2”, “Csf3”, and “Pfam08798”.
In the interests of compact prosecution, the claim listing has been entered. However, future claim listings must include the correct status of all claims, including appropriate mark-ups for changes to the claims, in order for the claim listing to meet the requirements for entry under 37 CFR 1.121(c) or a Notice of Non-Compliant Amendment will be mailed to applicant.
37 CFR 1.821-1.825
In response to the Notice to Comply accompanying the prior action, Applicant submitted a substitute specification, replacement drawing sheets, and a revised sequence listing. However, the substitute specification and replacement drawing sheets failed to address all the issues identified in the prior action, as discussed in more detail below. Additionally, the new sequence listing has new deficiencies, as outlined below.
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), 3rd 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), 3rd 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.
The substitution specification filed 06 April 2026 inserted SEQ ID NOs into the text for all of the sequences which were missing identifiers within Table 1 and [00840]. However, [00164] still recited sequences without SEQ ID NOs accompanying the recitations; specifically, “GGGS”, “(GGGGGS)3-15”, “(GGGGS)3-11”, and “GGGGS” in lines 16, 19, 19, and 20, respectively, of [000164] as filed 06 April 2026 without any accompanying sequence identifier. Additionally, [00165] still recites “(GGGGS)1” in line 4 without an accompanying sequence identifier. As such, the specification filed 06 April 2026 has not been entered.
The drawings replacement sheets submitted 06 April 2026 insert sequence identifiers for most of the sequences recited in Figures 2 and 4. However, the consensus sequences at the top of each figure are still missing sequence identifiers. Appropriate correction by either submitting new replacement sheets and/or by amending the Brief Description of the Drawings within a substitute specification is required.
If the unidentified sequences of specification paragraphs [00164-00165, 00840], Table 1 (e.g., Csf2 (Cas7 like), 3rd 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), 3rd 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.
Further, the revised sequence listing filed 06 April 2026 comprises additional sequences which were previously recited in the specification Table 1 and drawings Figures 2 and 4. However, the sequence listing is not in compliance with all of the requirements of 37 CFR 1.821-1.825, WIPO Standard ST.25, and/or 37 CFR 1.831-1.835 and 1.839. Specifically, validation of the sequence listing identified the following noncompliance:
DEFECTIVE: This validation report concerns the sequence listing filed 04-06-2026 08:48:19 and indicates the errors found by the USPTO during validation of the sequence listing. Any resolution of the errors identified in this validation report should not be construed as meaning that the sequence listing will comply with all of the requirements of 37 CFR §§ 1.821- 1.825, WIPO Standard ST.25, 37 CFR §§ 1.831-1.835 and 1.839, or WIPO Standard ST.26. For any sequence listing related questions or concerns, the Applicant is invited to contact the USPTO Sequence Help Desk at 571-272-2510 or SequenceHelpDesk@USPTO.GOV
Reviewer's Comments:
1. Reply in <213> is of a higher taxonomic rank than genus:
Numeric identifier <213> can only be one of four choices: Genus species name, Virus name, Unknown, or Artificial Sequence.
The reply in numeric identifier <213> in SEQ ID NOs: 1214-1252 is a higher taxonomic rank than a Genus species. If the "Genus species" name is not known, the correct reply for numeric identifier <213> is "Unknown."
When using "Unknown" for numeric identifier <213>, a mandatory feature is required to explain the source of the genetic material. The feature consists of numeric identifier <220>, which remains blank and numeric identifier <223>, which states the source of the genetic material. Please make all necessary changes.
2808. W402 Undefined organism found in <213> in SEQ ID (1214)
2809. W402 Undefined organism found in <213> in SEQ ID (1215)
2810. W402 Undefined organism found in <213> in SEQ ID (1216)
2811. W402 Undefined organism found in <213> in SEQ ID (1217)
2812. W402 Undefined organism found in <213> in SEQ ID (1218)
2813. W402 Undefined organism found in <213> in SEQ ID (1219)
2814. W402 Undefined organism found in <213> in SEQ ID (1220)
2815. W402 Undefined organism found in <213> in SEQ ID (1221)
2816. W402 Undefined organism found in <213> in SEQ ID (1222)
2817. W402 Undefined organism found in <213> in SEQ ID (1223)
2818. W402 Undefined organism found in <213> in SEQ ID (1224)
2819. W402 Undefined organism found in <213> in SEQ ID (1225)
2820. W402 Undefined organism found in <213> in SEQ ID (1226)
2821. W402 Undefined organism found in <213> in SEQ ID (1227)
2822. W402 Undefined organism found in <213> in SEQ ID (1228)
2823. W402 Undefined organism found in <213> in SEQ ID (1229)
2824. W402 Undefined organism found in <213> in SEQ ID (1230)
2825. W402 Undefined organism found in <213> in SEQ ID (1231)
2826. W402 Undefined organism found in <213> in SEQ ID (1232)
2827. W402 Undefined organism found in <213> in SEQ ID (1233)
This error has occurred more than 20 times, will not be displayed.
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.
A revised sequence listing in compliance with all of the requirements of 37 CFR §§ 1.821- 1.825, WIPO Standard ST.25, 37 CFR §§ 1.831-1.835 and 1.839, or WIPO Standard ST.26.
Drawings
As discussed above under 37 CFR 1.821-1.825, the replacement sheets submitted 06 April 2026 for Figures 2 and 4 are still lacking sequence identifiers for the consensus sequences at the top of each figure. However, because the sequence identifiers may be provided within the Brief Description of the Drawings in the specification, the replacement sheets have been entered.
Specification
As discussed above under 37 CFR 1.821-1.825, the substitute specification filed 06 April 2026 has not addressed all of the issues identified in the prior action in that not all presented amino acid sequences in [00164-00165] having at least 4 specifically recited residues have accompanying SEQ ID NOs recited with each recitation of the sequence within the text nor are all of the sequences presented in the Drawing labeled with a SEQ ID NO: either within the figure or within the Brief Description of the Drawings.
Accordingly, the amendment to the specification of the disclosure filed 06 April 2026 has not been entered.
Claim Objections
The objection to amended and original claims 1-2, 18, 22, 34, and 35 for reciting abbreviations without first writing out the terms for which they are abbreviated and for underlining of previously presented text is withdrawn in view of the amendment to claims.
The objection to claim 5 for reciting, “sequence listed in Table 1”, is withdrawn in view of the cancellation of claim 5.
Claim Rejections - 35 USC § 112(b)
The rejection of amended, previously presented, original, and cancelled claims 1-2, 5-6, 9, 11-13, 15, 17-19, and 22-24 under 35 U.S.C. 112(b) as failing to particularly point out and distinctly claim the subject matter which the inventor(s) regards as the invention for multiple issues of indefiniteness is withdrawn over cancelled claim 5 and maintained over amended, previously presented, and original claims 1-2, 6, 9, 11-13, 15, 17-19, and 22-24. Applicant's amendments to the claims and arguments have been fully considered but have not been found persuasive in overcoming the rejection for reasons of record as discussed in detail below.
Applicant’s amendments to the claims have overcome a majority of the issues of indefiniteness identified in the prior action except as discussed below, but have also introduced new issues of indefiniteness as discussed below.
Independent claim 1 recites, “the guide-Cas system complex” in line 6 and again in line 10. There is still insufficient antecedent basis for these limitations in the claim. Claim 1 recites “at least one guide molecule comprising an engineered heterologous guide sequence capable of complexing with the Type IV Cas system” in lines 4-5 and “at least one guide molecule comprising an engineered heterologous guide sequence capable of complexing with the Type I Cas system” in lines 8-9, but does not have any prior recitations of any “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 molecule comprising an engineered heterologous guide sequence capable of complexing with the [Type IV or Type I] 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 10 in that there are two prior recitations of two different Cas systems which can be complexed with guides.
Amended claims 6 and 9 were rejected for reciting “the Class I, Type IV Cas system target sequence” in lines 1-2 of each claim. There is insufficient antecedent basis for this limitation in the claim. None of amended independent claim 1, upon which amended claims 6 and 9 depend, claim 6, nor 9 have any prior recitation of any “a Class I, Type IV Cas system Cas target sequence”. Each of claim 6 and 9 still recite “the Class I, Type IV Cas system target sequence” in lines 1-2 of each claim, and none of claims 1, 6, nor 9 still have any prior recitation of any “a Class I, Type IV Cas system Cas target sequence”.
Claims 6 and 9 were also rejected for reciting “target sequence comprises a protospacer adjacent motif (PAM) at the 5’ side of the target sequence” (claim 6) and “target sequence comprises a 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. The amendments to these claims have partially addressed this issue by specifying that the PAM is adjacent to the 5’ side or the 3’ side of a target sequence, respectively. However, issues of indefiniteness remain/ are generated by Applicant’s amendments.
Claims 6 and 9 now recite, “wherein the Class 1, Type IV Cas system target sequence comprises a [PAM] adjacent to the [5’ or 3’] side of a target sequence”, which is indefinite because it is unclear whether the “a target sequence[s]” which are adjacent to the PAMs are meant to be the same target as “the Class 1, Type IV Cas system target sequence”, are meant to be a part of the “the Class 1, Type IV Cas system target sequence”, are meant to overlap with “the Class 1, Type IV Cas system target sequence”, or are meant to be distinct/ fully adjacent to “the Class 1, Type IV Cas system target sequence”. Further, if the “a target sequence[s]” which are adjacent to the PAMs are meant to be the same target as “the Class 1, Type IV Cas system target sequence”, then it is unclear how the target can comprise a PAM adjacent to itself.
Amended claim 17 was rejected for reciting “the Cas protein” and “the guide-Cas protein complex” in lines 2 and 2-3, respectively, wherein there was 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. Amended claim 17 now recites, “further comprising a plurality of guide molecules capable of complexing with a Cas protein and directing binding of a guide-Cas protein complex to one or more target polynucleotides”, which is now indefinite in that it is unclear whether the plurality of guide molecules are meant to be the same “at least one guide molecule” recited in claim 1. Additionally, recitation of “a Cas protein” encompasses any Cas protein and is not limited to the Cas proteins associated with the Type IV or Type I Cas systems recited in claim 1. Thus, if the plurality of guide molecules recited in claim 17 are meant to be the same “at least one guide molecule” recited in claim 1, it is further unclear whether the plurality of guide molecules are meant to be capable of complexing with the Type IV or Type I Cas system as well as any other Cas protein of any type to direct binding of any guide-Cas protein complex to any one or more target polynucleotides. Additionally, it is unclear whether the guide-Cas protein complex is meant to be made up of the guide molecules capable of complexing with a Cas protein as recited in claim 17 or the guide molecules recited in claim 1, and whether the guide-Cas protein complex is meant to comprise the specific Cas protein which the guide molecules of claim 17 are capable of complexing with or a Cas protein associated with the Cas systems recited in claim 1. For example, it is unclear whether the “a guide-Cas protein complex” of claim 17 is the “the guide-Cas system complex” recited in either line 6 or 10 of claim 1 or whether it is meant to be an additional guide-Cas protein complex.
Applicant amended independent claim 18 to recite, “a class 1, Type IV Cas protein” in lines 4-5 and “a guide-Cas protein complex in line 5, which is still indefinite because although “a class 1, Type IV Cas protein” now encompasses any class 1, Type IV Cas protein not limited to proteins which comprise DinG protein with a length less than 600 amino acids, having two different references to Cas proteins makes it unclear which Cas protein the recitation of “a guide-Cas protein complex” is referencing. For example, it is unclear whether the “a guide-Cas protein complex” encompasses the class 1, Type IV Cas protein comprising DinG protein with a length less than 600 amino acids, the any class 1, Type IV Cas protein, and/or any other Cas protein of any class or type.
Independent claim 18 additionally still recites, “the guide-Cas protein complex” in line 10, which still has insufficient antecedent basis in that it is unclear whether “the guide-Cas protein complex” is meant to be the same “a guide-Cas protein complex” recited in line 5, or which guides or Cas proteins are meant to be comprised in “the guide-Cas protein complex”, such as the guide molecules recited in line 4 or 9 and the Cas proteins recited in lines 2, 3, 4-5, 7, 8, or 9.
As such, the metes and bounds of the claims still cannot be determined.
Applicant argues that:
Amendments to claim 1 clarify the antecedent basis for “the guide-Cas system complex” by specifying “the Type IV Cas system” and “the Type I Cas system”;
The amendments to claims 6 and 9 remove the phrase “the Class 1, Type IV Cas system target sequence” and instead recite “the target polynucleotide comprises a PAM sequence adjacent to the 5’ side [or 3’ side] of a target sequence”, which properly references “the target polynucleotide” recited in claim 1 and eliminates the antecedent basis issue, wherein “adjacent to” clarifies that the PAM is positioned next to, but not within, the target sequence; and
Amendment of claims 17 and 18 to recite, “a Cas protein” and “a guide-Cas protein complex” throughout eliminates the antecedent basis issues by properly introducing these elements without assuming prior reference.
However, that is not agreed.
Regarding Applicant’s argument 1), as discussed above, amended independent claim 1 has no recitation of any “a guide-Cas system complex”. Additionally, to the extent that the complex is implied by the claim to refer to a complex formed between the guide comprised within- and capable of complexing with- the Cas system and the rest of the Cas system within which it is comprised, the second recitation of “the guide-Cas system complex” could be referring to either of the previously recited Cas systems and their accompanying guides, and so further lacks antecedent basis.
Regarding Applicant’s argument 2), note that the claims as filed were not amended to recite what Applicant argues they were amended to recite. As such, the claims have not benefited from the clarity that would have been provided by the amendments as argued by Applicant.
Regarding Applicant’s argument 3), as discussed above, some of the antecedent basis issues remain as well as new issues associated with multiple uses of “Cas protein” and “guide molecule” which renders the claims indefinite.
Accordingly, Applicant’s arguments do not overcome a finding of indefiniteness under 35 U.S.C. 112(b), and the rejection is maintained.
Claim Rejections - 35 USC § 101
The rejection of amended, previously presented, original, and cancelled claims 1-2, 5-6, 9, 11-12, 17-18, 22-24, and 34-37 under 35 U.S.C. 101 as being directed to a product of nature without significantly more is withdrawn over amended and cancelled claims 1-2, 5-6, 9, 11-12, 17, 24, and 34-36 and maintained over amended and original claims 18, 22-23, and 37. Applicant's amendments to the claims and arguments have been fully considered but have not been found persuasive in overcoming the rejection for reasons of record as discussed in detail below.
Independent claims 1 and 34 have been amended to recite inclusion of “at least one guide molecule comprising an engineered heterologous guide sequence” in claim 1 lines 4-5 and 8-9 and claim 34 lines 2-3. As such, amended claims 1 and 34 no longer encompass a naturally occurring composition. Dependent claims which fully incorporate amended claims 1 and 34 likewise no longer encompass a naturally occurring product of nature.
However, amended independent claim 18 has not been amended to recite a heterologous guide RNA molecule nor any other limitation which would distinguish it from its naturally occurring counterpart, as discussed in the prior action. Amended dependent claim 22, which depends on claim 18, likewise still only recites naturally occurring components. Previously presented claim 23, which encompasses amended independent claim 18, merely recites a vector comprising any one or more polynucleotide recited within independent claim 18, and as such encompasses a naturally occurring plasmid comprising the naturally occurring polynucleotides. Original claim 37 recites a composition comprising any one or more polynucleotides encoding one or more components of the composition of claim 34, and as such does not require the heterologous guide RNA and encompasses a composition comprising only the naturally occurring polynucleotides which would be found together in nature.
Therefore, Applicant’s amendments have not distinguished the compositions of claims 18, 22-23, and 37 from a product of nature and so have not overcome the rejection under 35 U.S.C. 101.
Applicant argues that the recited “at least one guide molecule comprising an engineered heterologous guide sequence capable of complexing with the [Type IV or Type I] Cas system and directing binding of the guide-Cas system complex to a target polynucleotide” creates a programmable system for targeted genome modification, using human-designed guides rather than natural CRISPR arrays for bacterial immunity, and accordingly, the system comprises markedly different characteristics than a naturally occurring system.
However, this is agreed only in part. The recitation in the claims of “an engineered heterologous guide sequence” has indeed rendered claims 1 and 34 distinct from their naturally occurring counterpart, along with all dependent claims which fully incorporate all of the limitations of independent claims 1 and 34. However, as discussed above, independent claim 18 has not been amended to incorporate an engineered heterologous guide sequence, and as such claim 18 and claims dependent on claim 18 are not distinguishable from their naturally occurring counterparts. Additionally, claim 37 does not require all of the recited sequences of independent claim 34, and as such does not require inclusion of a heterologous guide RNA.
As such, Applicant’s arguments do not overcome a finding that claims 18, 22-23, and 37 are directed to a product of nature, and the rejection is maintained.
Claim Rejections - 35 USC § 103
The rejection of amended, previously presented, original, and cancelled claims 1-2, 5-6, 9, 11-13, 15, 17-19, 22-24, and 34-37 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], is withdrawn over cancelled claim 5 and maintained over amended, previously presented, and original claims 1-2, 6, 9, 11-13, 15, 17-19, 22-24, and 34-37. Applicant's amendments to the claims and arguments have been fully considered but have not been found persuasive in overcoming the rejection for reasons of record as discussed in detail below.
Applicant amended to claims to address issues of indefiniteness, formalities, and to partially distinguish the compositions from products of nature. Applicant did not amend the claims to incorporate any new limitations which would alter the scope of the claims sufficiently to overcome a finding of obviousness under 35 U.S.C. 103 over the cited references.
Applicant argues that:
Hou provides no motivation to select Sulfuritalea hydrogenivorans specifically from a long list of possible alternatives;
The GenBank and InterPro references cannot qualify as prior art under 35 U.S.C. 102(a)(1) because they became available after the effective filing date of the claimed invention; and
Makarova, Crowley, and Taylor cannot bridge the above-mentioned gaps because they do not point to Sulfuritalea or provide motivation to investigate that organisms specifically.
However, this is not agreed.
In response to Applicant’s arguments against the references individually, it is noted that the test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). One cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Further, the Examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In addition, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Specifically, regarding Applicant’s argument 1), Hou was cited for teaching 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]. Applicant argues that Hou did not teach motivation to specifically select Sulfuritalea hydrogenivorans; however, Hou teaches specifically to select a gene encoding a Cas endonuclease identified, derived, or isolated from any organism selected from the list recited in [0008]. Further, a lack of motivation in the primary reference is not relevant in that selection of S. hydrogenivorans is not a modification of the primary reference but is a direct teaching of the primary reference.
Note also that amended independent claim 1 as written is not limited to the sequence of SEQ ID NO: 458, which was merely elected as a species for initial examination from a list of over 400 sequences of Class I, Type IV Cas system Cas proteins recited in instant Table 1, previously claimed by Applicant, and presently encompassed by the genus of independent claim 1. Amended independent claim 1 as written is broadly directed to encompass all Class I, Type IV Cas systems comprising a helicase comprising a DinG and HNH domain wherein the helicase is less than 600 amino acids and all Class I, Type I Cas systems comprising an HNH domain, wherein the HNH domain is less than 400 amino acids in length, wherein the systems comprise the accompanying heterologous guide RNAs. Accordingly, given the scope of the claim, the selection specifically of S. hydrogenivorans from a broad list of approximately 200 species taught by Hou as a representative teaching is not an unreasonable singling out which would require teachings that it was “uniquely preferred, critical, or specially advantageous relative to the rest of the list of Hou” [Applicant’s Remarks page 16 ¶ 4].
Regarding Applicant’s argument 2), note that GenBank and InterPro were cited for teaching inherent properties of the Cas protein from S. hydrogenivorans taught by Hou. As discussed in the prior action, 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).
Wildtype sequences are inherent features of a bacterial species. As taught by GenBank, the sequence of instant SEQ ID NO: 458 is the wildtype sequence of an HNH endonuclease from Sulfuritalea sp. [page 1 title, page 2 lines 14-15, 23, 26-35]. InterPro was cited for teaching 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]. Therefore, GenBank and InterPro teach inherent features of the claimed and elected Cas system.
Accordingly, by teaching to select a Cas endonuclease from S. hydrogenivorans, Hou is teaching to select a Class I, Type IV Cas system protein which encompasses the MAG: HNH endonuclease/helicase taught by GenBank and InterPro and which has less than 600 amino acids in length. Additionally, protein domain structures are inherent properties of the amino acid sequence of the protein, and so the MAG: HNH endonuclease taught by Hou in view of GenBank and InterPro is a teaching of a helicase comprising a DEAD/DEAH-box helicase domain/DinG helicase domain and an HNH domain.
Therefore, because GenBank and InterPro teach inherent features of the Cas endonuclease as taught by Hou, there is no requirement that the teachings of GenBank and InterPro must have been available prior to the effective filing date of the instantly claimed invention.
Regarding Applicant’s argument 3), note that GenBank and InterPro, which are legitimate references teaching inherent properties of the Cas systems taught by Hou prior to the effective filing date of the instantly claimed invention, were cited for teaching the connection between the teachings of Hou and the elected sequence of instant SEQ ID NO: 458 as well as the connection between the Cas protein taught by Hou and the claimed domain structures. As discussed above, Hou teaches to select a Cas system from Sulfuritalea hydrogenivorans, which is specifically recited within the list of species from which to select in [0008]. Makarova was cited for teaching 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], thereby teaching that the Cas system taught by Hou, as evidenced by GenBank and InterPro, meets all the limitations of instant claim 1. Crowley and Taylor were cited for teaching dependent limitations. As discussed above, motivation to specifically select the Sulfuritalea hydrogenivorans Cas system is not relevant in that Hou teaches specifically to select a Cas system from any of the species listed, which includes Sulfuritalea hydrogenivorans, such that selecting Sulfuritalea hydrogenivorans does not constitute a modification of the primary reference to arrive at the instantly claimed and elected invention.
Accordingly, Applicant’s arguments do not overcome a finding of obviousness under 35 U.S.C. 103 over Hou, GenBank, InterPro, Makarova, Crowley, CRISPRone, and Taylor, and the rejection is maintained.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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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
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