DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election without traverse of Group II, claims 4-5, 8, 10, 14-17, 27, 33, 36-37, 47-48, 50, 53-54, in the reply filed on 07/20/2026 is acknowledged.
Election of species is withdrawn.
Claims 1, 62, 69 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 07/20/2026.
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.
Claim 47 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 47 originally depends on claim 4 and adds a limitation of amount of Cas7 protein being higher than other components. Claim 4 defines the system as just a number of components, without specifying any amount of any of them. Thus, the metes and bounds of claim 37 are undefined, because it is impossible to figure out the excess amount if regular amount is not defined in the claim.
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 37 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.
Claim 37 depends on claim 4, which recites system for effector domain recruitment to a target nucleic acid, and adds a limitation that such target nucleic acid comprises a promoter or upstream activator sequence. The target nucleic acid is not a part of the system of claim 4, therefore such limitation of claim 37 does not affect the system. Thus, claim 37 does not further limit claim 4.
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 § 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 4-5, 8, 10, 14-17, 27, 33, 36-37, 47, 53-54 are rejected under 35 U.S.C. 101 because the claimed invention is directed to natural product without significantly more. The claim(s) recite(s) systems comprising at least one Cas protein, at least one transposon-associated protein and a guide RNA, wherein at least one Cas protein and at least one transposon-associated protein comprises at least one effector domain such as transcription activator or nucleic acids encoding such system. According to instant specification “effector domain” can be essentially any type of functional entity, therefore such effector domain reads on natural promoter of respective protein.
Subject Matter Eligibility Test for Products and Processes
Step 1 - Is the Claim to a Process, Machine, Manufacture or Composition of Matter? YES
The instant claims are directed to a system (e.g., cell) comprising Cas protein that comprises Cas5, Cas6, Cas7, and Cas8, a transposon-associated protein such as TnsA, TnsB, TnsC, and TniQ and gRNA, which encompasses "naturally" occurring cells having said elements. Thus, the instant claims are directed to a statutory category (e.g., a composition of matter) and recite nature based products. The markedly different analysis is used to determine if the nature-based products fall under the "product of nature" exception.
Step 2A Prong One - Is the Claim Directed to a Law of Nature, a Natural Phenomenon, or an Abstract Idea (Judicially Recognized Exceptions)? YES
As indicated above, the instant claims are directed to a system (e.g., cell) comprising Cas protein that comprises Cas5, Cas6, Cas7, and Cas8, a transposon-associated protein such as TnsA, TnsB, TnsC, and TniQ and gRNA that are considered to be naturally occurring, which is ineligible subject matter. The cells comprising the recited elements encompassed by the instant claims are considered to be structurally identical (e.g., same genetic structure) to those that are naturally occurring. For example, Peters et al (Molecular Microbiology, 2019, 112(6), 1635-1644) indicates many bacterial and archaeal genomes have Tn7-like transposon systems (e.g., TnsA, TnsB, TnsC and TniQ) and CRISPR-Cas systems (see Abstract, Figure 2C). Klompe et al (Nature, 2019, Vol. 571, pages 219-225, cited from IDS) indicates Vibrio cholerae strain Tn6677 encodes a Tn7-like transposon system (e.g., having the elements TnsA, TnsB, TnsC and TniQ) (see paragraph bridging pages 219 and 220; and Fig. 1A). McDonald et al (BMC Genomics, 2019, Vol. 20, No. 1, pages 1-23) indicates that genome of Vibrio cholerae (e.g., He-45, i.e., Tn6677) naturally has a CRISPR-Cas system (e.g., e.g., Cas5, Cas6, Cas7 and Cas8, Type I-F system) (see Abstract; paragraph bridging pages 1 and 2 to paragraph bridging pages 6 and 7; page 2, left column, 1st full paragraph; paragraph bridging pages 9 and 10; and Figs. 2b and 5). Oost et al (Cell Research, 3 March 2020, Vol. 30, pages 193-194) indicates Vibrio cholera Tn6677 encodes a type I-F CRISPR-Cas system composed of Cas6, Cas7, and fused Cas8-Ca5 along with a transposon system composed of TnsA, TnsB, TnsC, and TniQ (see page 1, paragraph bridging left and right columns; and Fig. 1). Therefore, the systems (e.g., cells) encompassed by the instant claims have no different functional characteristics than the naturally occurring cells (e.g., Vibrio cholera) and, therefore, are not eligible since they are not different enough from what exists in nature to avoid improperly tying up future use and study of naturally occurring products. In other words, the claimed system (e.g., cells) are not markedly different, from the naturally occurring counterparts and, thus, are directed to a "product of nature" exception.
Step 2A Prong Two - Is the claim as a whole integrates the recited judicial exception into a practical application of the exception? NO
Claims recite a system comprising a number of elements, which are natural products. The preamble of the claim 4 recites intended use of the system, but such intended use is not given patentable weight and does not integrate judicial exception into practical application.
Step 2B - Does the Claim Recite Additional Elements that Amount to Significantly More than the Judicial Exception? NO
Claims directed to an exception should be analyzed to determine whether any element, or combination of elements, in the claim is sufficient to ensure that the claims amount to significantly more than the exception. However, the claims do not include any additional features, singularly or in combination, that could add significantly more to the exception. For instance, the claimed system (e.g., cell), as encompassed by the instant claims, do not have different structural characteristics than those that are naturally occurring. Thus, the claims do not rise to the level of a marked difference, and the claimed gene products are considered "product of nature" exceptions. Accordingly, the instant claims do not qualify as patent-eligible subject matter.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 4-5, 16-17, 27, 37, 53, 54 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Scott et al (WO 2019/090175, May 2019, cited from IDS).
Concerning claims 4-5 Scott disclose a system comprising Cas protein and guide RNA complementary to a target nucleic acid (see lines 20-30 on page 2) and further comprising transposon-associated protein transposase (see lines 24-31 on page 4). Such elements of the system can be encoded by nucleic acid for expression in a cell and can be included in a vector, which comprises regulatory elements such as promoters (see lines 2-10 on page 4). Cas proteins can further comprise effector domains such as transcription activators (see lines 13-16 on page 17). A limitation “for effector domain recruitment” from preamble is of intended use and does not carry patentable weight.
Concerning claims 16-17 Scott disclose that transposase can comprise TniQ (see lines 1-2 on page 13).
Concerning claim 27 Scott disclose that Cas protein includes nuclear localization signal (see lines 30-31 on page 3).
Concerning claim 37 Scott disclose that target nucleic acid can comprise a promoter (see lines 25-26 on page 6).
Concerning claim 53 Scott disclose that transposon-associated protein and Cas protein can be fusion proteins (see lines 10-20 on page 17).
Concerning claim 54 Scott disclose that Cas protein and transposon-associated protein for a ribonucleoprotein complex with gRNA (see lines 7-10 on page 5).
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)(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) 4-5, 8, 10, 14-16, 27, 33, 36-37, 53-54 is/are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Zhang et al (US 2020/0190487, June 2020, filed December 2019, cited from IDS).
Concerning claims 4-5 Zhang disclose engineered nucleic acid targeting CRISPR-Cas system comprising Cas protein, transposase protein and a guide RNA capable of complexing with Cas protein and directing sequence specific binding of the guide-Cas protein complex to a target sequence of a target polynucleotide (see paragraphs [0008, 0012]). Cas protein can be associated with transcriptional activators (see paragraphs [0532-0533]). Such system can also include a donor polynucleotide, wherein the CRISPR-Cas complex directs the CRISPR-associated transposase to the target sequence and the CRISPR-associated transposase inserts the donor polynucleotide into the target polynucleotide at or near the target sequence (see paragraph [0017]). A limitation “for effector domain recruitment” from preamble is of intended use and does not carry patentable weight.
Concerning claims 8, 10, 14 Cas protein can be Cas7 or Cas12k (see paragraph [0158]).
Concerning claims 15-16 transposase protein can be derived from Tn7 transposon system and can be TnsB and TnsC (see paragraph [0009]).
Concerning claim 27 Cas protein and transposase can comprise a nuclear localization signal (NLS) (see paragraph [0364]).
Concerning claim 33 CRISPR-Cas system can be derived from Vibrio cholerae (see paragraph [0163]).
Concerning claim 36 guide RNA can be transcribed under control of RNA Polymerase II promoter (see paragraph [0181]).
Concerning claim 37 target nucleic acid can comprise a promoter (see paragraphs [1032, 1034]).
Concerning claim 53 Cas protein can be fusion protein (see paragraph [0163]) and can be fused with transposase (see paragraph [0129]).
Concerning claim 54 Cas protein, transposase and guide RNA form ribonucleoprotein complex (see paragraph [0452]).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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) 4-5, 8, 10, 14-17, 27, 33, 36-37, 47-48, 50, 53-54 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zhang, above, as applied to claims 4-5, 8, 10, 14-16, 27, 33, 36-37, 53-54, above, and further in view of Sloan et al (WO 2018/118587, June 2018) and Cameron et al (WO 2019/241452, December 2019).
Teachings of Zhang are discussed above. Specifically Zhang teach that Cas protein can be fused with transposase (see paragraph [0129]) and Cas protein can be associated with transcriptional activators (see paragraphs [0532-0533]).
Zhang do not teach TnsC comprising effector domain, or the system comprising Cas7 in greater abundance, or further comprising a sequence capable of forming a triple helix downstream of the sequence encoding Cas protein or the sequence encoding transposon- associated protein, or Cas protein or transposon-associated protein comprising a sequence of a ribosome skipping peptide.
Sloan teach compositions comprising mRNA encoding Cas protein, wherein such mRNA has triple helical structure at its 3’ end, which allows successful translation in vivo without the need of poly(A) tail (see last paragraph on page 3).
Cameron teach vectors for protein expression of several coding sequences simultaneously comprising ribosomal skipping peptides (see paragraph [00225]).
It would have been obvious to one of the ordinary skill in the art before the effective filing date of the claimed invention to modify compositions taught by Zhang by using TnsC protein comprising effector domain, or include in the system a sequence capable of forming a triple helix downstream of the sequence encoding Cas protein or include ribosome skipping peptide as taught by Zhang, Sloan and Cameron. One of the ordinary skill in the art would be motivated to do so because Zhang teach association of Cas peptide with transposase and transcriptional activator, leading to complex involving transposase such as TnsC and transcriptional activator (effector domain). Further Sloan suggest including triple helix structures in the 3’ end of coding sequence of Cas protein in place of poly(A) tail, which can be included in Zhang system for successful translation of Cas protein. Further Cameron teach use of ribosomal skipping proteins for simultaneous expression of several proteins, which can be used in Zhang system for expression of Cas proteins and transposases simultaneously. Lastly, the amount of Cas7 protein can be optimized and used in abundance over other proteins as a part of ordinary system optimization.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 4-5, 8, 10, 14-17, 27, 33, 36-37, 47-48, 50, 53-54 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 10,947,534 in view of Zhang, Sloan and Cameron, above. Claims from ‘534 teach CRISPR-Cas system comprising Cas proteins, guide RNA and transposon-associated proteins, same as in instant claims. Teachings of Zhang, Sloan and Cameron are discussed above. It would have been obvious to include elements taught by Zhang, Sloan and Cameron in system from ‘534 arriving at instant invention.
Claims 4-5, 8, 10, 14-17, 27, 33, 36-37, 47-48, 50, 53-54 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 12,331,292 in view of Zhang, Sloan and Cameron, above. Claims from ‘292 teach methods of using of CRISPR-Cas system comprising Cas proteins, guide RNA and transposon-associated proteins, same as in instant claims. Teachings of Zhang, Sloan and Cameron are discussed above. It would have been obvious to include elements taught by Zhang, Sloan and Cameron in system from ‘292 arriving at instant invention.
Claims 4-5, 8, 10, 14-17, 27, 33, 36-37, 47-48, 50, 53-54 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 13-32 of copending Application No. 19/202829 in view of Zhang, Sloan and Cameron, above. Claims from ‘829 teach CRISPR-Cas system comprising Cas proteins, guide RNA and transposon-associated proteins, same as in instant claims. Teachings of Zhang, Sloan and Cameron are discussed above. It would have been obvious to include elements taught by Zhang, Sloan and Cameron in system from ‘829 arriving at instant invention.
This is a provisional nonstatutory double patenting rejection.
Claims 4-5, 8, 10, 14-17, 27, 33, 36-37, 47-48, 50, 53-54 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 8, 10-11, 22, 31, 33, 36-37, 113, 115, 120-122, 124, 127-128 of copending Application No. 18/567617 in view of Zhang, Sloan and Cameron, above. Claims from ‘617 teach CRISPR-Cas system comprising Cas proteins, guide RNA and transposon-associated proteins, same as in instant claims. Teachings of Zhang, Sloan and Cameron are discussed above. It would have been obvious to include elements taught by Zhang, Sloan and Cameron in system from ‘617 arriving at instant invention.
This is a provisional nonstatutory double patenting rejection.
Conclusion
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/EKATERINA POLIAKOVA-GEORGANTAS/Primary Examiner, Art Unit 1637
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