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 .
The preliminary amended claim set dated 3/14/2023 is under consideration.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-13, in the reply filed on 10/22/2025 is acknowledged.
The restriction requirement between Groups I and IV is withdrawn. Claim 20 is included with the election of Group I.
In view of the above noted withdrawal of the restriction requirement, applicant is advised that if any claim presented in a 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Once a restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable.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.
Claims 15-19 and 21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10/22/2025.
Priority
The present application is a 371 national stage entry of PCT/US2021/051053 (field 9/20/201), which claims benefit of US provisional application 63/080,253 (filed 9/18/2020).
Priority is recognized.
Information Disclosure Statement
The listing of references in the specification or the citation of references throughout the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892 or cited on a submitted IDS, they have not been considered.
Claim Interpretation
The claims include limitations that are “optional”. Claim scope is not limited by claim language that makes optional, but does not require steps to be performed. MPEP 2111.04.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-13 and claim 20 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.
Regarding claim 1, the claim states “activation of the Type III Cas protein as a non-specific nuclease is sustained at high levels and is not self-limited”, which is a description of a property and/or intended use of the claimed product. It is unclear what structural elements are required for “an accessory nuclease activator of a Type III Cas protein” to have the recited property or in order for it to be used as stated.
Claims 2-13 depend from claim 1 and are rejected for the same reason.
Claim 20 requires the product of claim 1, and thus is rejected for the same reason.
Regarding claim 2, the claim states “the Type III Cas protein is Csm6 or Csxl, optionally a T. thermolphilus (TtCsm6) protein”, which describes a structural element not required by the claimed product. It is unclear what additional structural elements are required by claim 2 for the “accessory nuclease activator” of claim 1, if any.
Regarding claim 8, the claim references Table 3, which sets forth molecules. The claim is incomplete based on the reference to incorporate the table recited in the claim. Claims are to be complete in themselves, and incorporation by reference of a table is a necessity doctrine and not one of convenience. See MPEP 2173.05(s).
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 20 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Regarding claim 20, the claim is an dependent claim as it refers to a previously set forth claim and requires all the elements of claim 1. The claim fails to include any additional elements beyond that of claim 1 and does not further limit any of the elements of claim 1.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-11, 13 and 20 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Savage (WO 2021/236651 A1; priority claim to 5/19/2020).
Claim(s) 1-11, 13 and 20 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Savage (US 2024/0141412 A1; priority claim to 5/19/2020).
The ‘412 publication is a 371 national stage entry of the PCT application published as the ‘651 publication. The two publications have the same disclosure based on their relationship. The following rejections include citations to the ‘651 publication.
Regarding claim 1, Savage teaches a caged activator of having the sequence 5’ AAAAUUUUUU 3’ or 5’ fA-fA-fA-AAAAAAA 3’ (para. 180).
Regarding claim 2, the claim does not specify any structural elements beyond that of claim 1.
The claim limits a “Type III Cas Protein” which is not a structural feature of the claimed composition.
Savage anticipates claim 2 for the same reason as claim 1.
Regarding claim 3, as noted above Savage teaches the sequence 5’ AAAAUUUUUU 3’, which comprises the linear oligoadenylate AAAA.
Regarding claims 3, 4 and 6, as noted above Savage teaches the sequence 5’ fA-fA-fA-AAAAAAA 3’, which comprises the linear oligoadenylate fA-fA-fA-A including the modified base fA.
Regarding claim 5, as noted above Savage teaches the sequences 5’ AAAAUUUUUU 3’ and 5’ fA-fA-fA-AAAAAAA 3’, which each includes a linear A4 oligoadenylate.
It is also noted the 5’ fA-fA-fA-AAAAAAA 3’ sequence includes an A6 oligoadenylate.
Regarding claim 7, as noted above Savage teaches the sequence 5’ fA-fA-fA-AAAAAAA 3’, which comprises a fA substitution at in the second position of the A4 oligoadenylate fA-fA-fA-A (emphasis added) or in the third position of the A6 oligoadenylate fA-fA-fA-AAA (emphasis added).
Regarding claim 8, as noted above Savage teaches the sequence 5’ AAAAUUUUUU 3’, which is SEQ ID NO: 1 of Table 3 in the instant specification.
Regarding claim 9, as noted above Savage teaches the sequence 5’ AAAAUUUUUU 3’, which has the A4 oligonucleotide AAAA and the additional sequence UUUUUU.
Regarding claim 10, as noted above Savage teaches the sequence 5’ AAAAUUUUUU 3’, which is cleaved by LbuCas13 to generate A4>P (para. 180).
Regarding claim 11, as noted above Savage teaches the sequence 5’ AAAAUUUUUU 3’, which includes a linear polyU sequence of 6 U residues.
Regarding claims 1 and 13, Savage teaches the sequence FAM/rArArArArA/3IABkFQ (p. 91, SEQ ID NO: 114), which includes a linear A4 oligoadenylate.
Regarding claim 20, the claim only requires the activator of claim 1. Savage anticipates claim 20 for the same reason as claim 1.
Claim(s) 1-6, 9-13 and 20 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Gootenberg (Science. 2018. 360(6387):439-444 and Supplementary Materials).
Regarding claim 1, Gootenberg teaches cyclic adenylate molecules or linear adenine homopolymers terminated with a 2’,3’-cyclic phosphate were known (p.3, last paragraph).
These molecules have all the structural features of the product of claim 1 in view of the instant specification. It is also noted that Gootenberg states these molecules activate a CRISPR type-III effector nuclease (p. 3, last paragraph).
Regarding claim 2, the claim does not specify any structural elements beyond that of claim 1.
The claim limits a “Type III Cas Protein” which is not a structural feature of the claimed composition.
Gootenberg anticipates claim 2 for the same reason as claim 1.
Regarding claim 3, as noted above, Gootenberg teaches cyclic adenylate molecules or linear adenine homopolymers terminated with a 2’,3’-cyclic phosphate were known. These molecules are examples of “cyclic and/or linear oligoadenylates”.
Regarding claims 1, 3, 4 and 6, Gootenberg teaches the sequence /56-
FAM/mArArUrGrGrCmAmArArUrGrGrCmA/3Bio/ (Table S5), which includes the linear oligoadenylate mAmArA containing a modified mA residue.
Regarding claims 1 and 4, Gootenberg teaches the sequence rArArArArArArUrUrUrUrU (Table S6), which comprise a an A6 oligonucleotide and a poly-U sequence as a “caging structure”.
Regarding claims 1 and 5, Gootenberg teaches a linear poly A sequence with lengths of 5, 6, 7 and 8 nucleotides (Table S6), each of which comprise an A4 oligoadenylate. The linear poly A sequences with lengths of 6, 7 and 8 nucleotides (Table S6), comprise an A6 oligonucleotide.
Regarding claims 1 and 9, Gootenberg teaches the sequence rArArArArArArUrUrUrUrU (Table S6), which comprises an A6 oligonucleotide and a poly-U sequence as an additional sequence.
Regarding claims 1, 10 and 11, as noted above, Gootenberg teaches the sequence rArArArArArArUrUrUrUrU (Table S6), which as a poly-U sequence that is preferred by a Cas13 enzyme (p. 4, first paragraph).
Regarding claims 1 and 12, Gootenberg teaches the sequence rCrUrCrCrCrUrArArUrArArCrArArUrUrUrArUrArArCrUrArUrUrCrCrUrArCrCrCrUrUrUrCrCrCrArArArArArArA (Table S5), which includes the underlined sequence that comprises an A4 or an A6 oligoadenylate and the bolded poly-C sequences.
Regarding claims 1 and 13, Gootenberg teaches the sequence 56-FAM/rArArArArA/3IABkFQ/ (Table S5), which includes the detectable label FAM along with a sequence comprising an A4 oligoadenylate.
Regarding claim 20, the claim only requires the activator of claim 1. Gootenberg anticipates claim 20 for the same reason as claim 1.
Claim(s) 1, 2, 3, 5 and 20 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Liu (JBC Papers In Press. “Chemistry of Class 1 CRISPR-Cas effectors: binding, editing, and regulation”. Published 8/14/2020).
Regarding claims 1, 3 and 5, Liu teaches a linear A6 with a 2’,3’-cyclic phosphate that activates Csm6 (p. 11 of 26, left column) and A3-6 cyclic oligoadenylates that activates an nuclease (Figure 3).
These molecules have all the structural features of the product of claim 1 in view of the instant specification.
Regarding claim 2, the claim does not specify any structural elements beyond that of claim 1.
The claim limits a “Type III Cas Protein” which is not a structural feature of the claimed composition.
Liu anticipates claim 2 for the same reason as claim 1.
Regarding claim 20, the claim only requires the activator of claim 1. Liu anticipates claim 20 for the same reason as claim 1.
Claim(s) 1-5, 8-12 and 20 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Pino (Entropy. 2013. 15:5362-5383).
Regarding claims 1, 3, 4, 5, 9, 11 and 12, Pino teaches an A12U12 and A12C12 oligonucleotide (p. 5364, 2.1.1. Oligonucleotides), which comprise an A4 or A6 oligoadenylate and a poly-U sequence or a poly-C sequence as additional sequences or “caging structures”.
These molecules have all the structural features of the product of claim 1 in view of the instant specification.
Regarding claim 2, the claim does not specify any structural elements beyond that of claim 1.
The claim limits a “Type III Cas Protein” which is not a structural feature of the claimed composition.
Pino anticipates claim 2 for the same reason as claim 1.
Regarding claim 8, as noted above Pino teaches an A12U12 oligonucleotide, which comprises SEQ ID NO: 1 of Table 3.
Regarding claim 10, as noted above Pino teaches an A12U12 oligonucleotide, which comprises as a poly-U sequence that is known to be preferred by a Cas13 enzyme.
Regarding claim 20, the claim only requires the activator of claim 1. Pino anticipates claim 20 for the same reason as claim 1.
Claim(s) 1-7, 9 and 20 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Copp (Nucleic Acids Research. 2017. 45(17):10321-10331).
Regarding claim 1, Copp teaches the sequences:
dT-r(AAAA)-rFA-r(AAA),
rF(AAAAAAAAAAA) and
r(AAAA)-rF(AAA)-r(AAAA) (Table 1),
which can be rewritten as:
dTrArArArArFArArArA,
rFArFArFArFArFArFArFArFArFArFArFArFA; and rArArArArFArFArFArArArArA, respectively.
These molecules have all the structural features of the product of claim 1 in view of the instant specification.
Regarding claim 2, the claim does not specify any structural elements beyond that of claim 1.
The claim limits a “Type III Cas Protein” which is not a structural feature of the claimed composition.
Copp anticipates claim 2 for the same reason as claim 1.
Regarding claim 3, as noted above Copp teaches the sequence rArArArArFArFArFArArArArA, which includes one or more linear oligonucleotides, which are underlined.
Regarding claims 4 and 6, as noted above Copp teaches the sequence rArArArArFArFArFArArArArA, which includes one or more linear oligoadenylates (underlined) comprising one or modified rFA residues.
Regarding claim 5, as noted above Copp teaches the sequence rArArArArFArFArFArArArArA, which includes the underlined linear A4 oligoadenylate.
Regarding claims 1, 5, and 7, as noted above Copp teaches the sequence rArArArArFArFArFArArArArA, which includes the underlined linear A4 oligoadenylate having a substituted rFA residue (bolded) at the second position.
Alternatively, as noted above Copp teaches the sequence rArArArArFArFArFArArArArA, which includes the underlined linear A6 oligoadenylate having a substituted rFA residue (bolded) at the third position.
Regarding claim 9, as noted above Copp teaches the sequence rArArArArFArFArFArArArArA, which includes the underlined linear A4 oligoadenylate and the additional bolded sequences.
Regarding claim 20, the claim only requires the activator of claim 1. Copp anticipates claim 20 for the same reason as claim 1.
Double Patenting
Applicant is advised that should claim 1 be found allowable, claim 20 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim 20 only requires the structure of claim 1 as an element and claim 1 encompasses additional elements. Thus, the scope of claim 1 and claim 20 are identical. There is nothing of record that demonstrates that a “kit” has any limiting definition that distinguishes the structure of its components from the structures of claim 1.
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-13 and 20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-8 and 11-33 of copending Application No. 17/926,441 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because the claim sets encompass overlapping subject matter.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPH G DAUNER whose telephone number is (571)270-3574. The examiner can normally be reached 7 am EST to 4:30 EST with second Fridays Off.
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/JOSEPH G. DAUNER/ Primary Examiner, Art Unit 1682