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 I in the reply filed on 26 March 2026 is acknowledged. It is noted that despite stating that the election was made without traverse, Applicant contends that claims 60 and 63 should be examined with Group I. Claims 60 and 63 are not rejoined at this time.
Claims 53-59 and 61 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 26 March 2026.
Applicant’s election without traverse of SEQ ID NOs: 13 and 31 in the reply filed on 26 March 2026 is acknowledged.
Claim Status
Claims 53-63 are pending.
Claims 54, 56, 60, and 62-63 are currently amended.
Claims 60 and 62-63 are withdrawn from consideration.
Claims 53-59 and 61 are examined on the merits.
Claim Objections
Claim 57 is objected to because of the following informalities: Paragraphs 2 and 3 recite, “wherein the at least one Cpf1 enzyme or active fragment thereof, or nucleic acid encoding the same, is selected from the group consisting of SEQ ID NOs:…” Paragraph 2 only recites SEQ ID NOs representing nucleic acid sequences and paragraph 3 only recites SEQ ID NOs representing amino acid sequences. This means that both paragraphs begin in an unnecessarily complex manner. It is suggested that paragraph 2 be amended as following: “wherein a nucleic acid sequence encoding the at least one Cpf1 enzyme or active fragment thereof is selected from the group consisting of…” and paragraph 3 is amended as following: “wherein the at least one Cpf1 enzyme or active fragment thereof is selected from the group consisting of…”
Claim Rejections - 35 USC § 112
Indefiniteness
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.
Claims 53-59 and 61 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 pre-AIA the applicant regards as the invention.
Claim 53 recites, “cellular system.” This is a term that does not have a clear art-recognized meaning, and the specification fails to define the phrase. As such the metes and bounds of the claim cannot be determined. Claims 54-59 and 61 are rejected for depending from an indefinite claim and failing to recite additional limitations that would render the claim definite.
Claim 54 recites, “wherein the first and second molecule are provided on a single transcript construct.” If the first and second molecule are part of a single transcript construct, they can only be reasonably construed as a single molecule. As such the metes and bounds of the claim cannot be determined.
Claim 58 is drawn to: the plant delivery system of claim 53 wherein the scaffold RNA sequence or sequence encoding the same is selected from the group consisting of SEQ ID NO:29-30. SEQ ID NOs: 29-30 both have thymine bases within the sequence; thus, they cannot be RNA sequences. It is unclear how these sequences can be the scaffold RNA sequence. As such, the metes and bounds of the claim cannot be determined.
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.
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.
Claim(s) 53-59, and 61 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zhong et al 2017 (Nature Chemical Biology 13:8, p. 839-841) and Wang et al 2017 (Molecular Plant 10: p.1011-1017), and further in view of Zhang et al (WO 2017184768 A1).
Zhong et al teach the use of Cpf1 proteins including LbCpf1 (same as instant SEQ ID NO:16) to mediate excision of guide RNAs from a 3’ UTR of a luciferase reporter gene which they allow the excised guide RNAs to direct LbCPF1 to cleave a target site in the host genome in mammalian cells. Excision of the guide RNAs stops expression of luciferase reporter (no light emitted).
Zhong et al do not teach that the system is for plants, uses a fluorescent reporter (luciferase is a luminescent reporter), or has the G532R/K595R substitutions.
Wang et al teach multiplex editing of rice using LbCpf1 and a single transcript which expresses multiple guide RNAs. The LbCpf1 and guide RNA transcripts are expressed using different promoters, ZmUbi and OsU6, respectively, and delivered in the same construct (1:1 ratio) (Figure 1 and caption). Wang et al further teach a scaffold sequence (which they refer to as a direct repeat) that is identical to the scaffold sequence in instant SEQ ID NO:30. Further, they teach that the scaffold sequence works for a LbCpf1 which is the same as instant SEQ ID NO:16 (Underlined in Supplemental sequence, p.18 of Supplemental content).
Zhang et al teach that a preferred embodiment of variant LbCpf1 enzyme comprises G532R/K595R substitutions (Table 2-3, 5) and that the variant enzyme has greater flexibility to target additional sites.
At the time of filing, it would have been prima facie obvious to combine the teachings of Zhong et al, Wang et al, and Zhang et al to arrive at the claimed invention. First, the art all concerns using the LbCpf1 to modify eukaryotic genomes. Wang et al teach that LbCpf1 can be useful for multiplex editing of the rice genome. A person of ordinary skill in the art would have been motivated to combine the teachings of Wang et al and Zhong et al to insert guide RNA encoding sequences within the 3’ UTR of a light emitting reporter (fluorescence and luminescence can be equivalently useful as long as the half-life of the protein is not long and half-lives of reporter enzymes are well-understood). This system would have allowed a person of ordinary skill to both track production of the guide RNAs within the target plant cell and to use a much wider array of promoter to express the guide RNAs as Pol II promoters can be used in this system. Further, it would have been prima facie obvious to use the variant LbCpf1 of Zhang et al as it allows for greater flexibility to target different sites in the host genome. As such, claims 53-59, and 61 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zhong et al and Wang et al 2017, and further in view of Zhang et al.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MATTHEW R KEOGH whose telephone number is (571)272-2960. The examiner can normally be reached M-Th 7-4:30, half day on Fridays.
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/MATTHEW R KEOGH/Primary Examiner, Art Unit 1663
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