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 .
Claim(s) 1, 16, 18-19, 21-22, 28-29, 39-40, and 47-50 are pending.
Preliminary Amendments
Applicant’s preliminary amendment filed on 07/20/2023 is acknowledged. The claims were amended to (1) cancel claims 2-3, 9-15, 20, 23-24, 31-38, and 41-46; and (2) amend claims 1, 4-6, 16-18, 21-22, 25-28, 30, and 39-40. The specification was amended to (1) update the “CROSS-REFERENCE TO RELATED APPLICATIONS” statement and (2) add the “REFERENCE TO AN ELECTRONIC SEQUENCE LISTING” statement.
Applicant’s preliminary amendment filed on 05/05/2026 is acknowledged. The claims were amended to (1) cancel claims 4-8, 17, 25-27, and 30; (2) amend claims 1, 18, 19, 21, 22, 28, 29, 39, and 40; and (3) add claims 47-50.
Election/Restrictions
Applicant’s election without traverse of Group I in the reply filed on 05/05/2026 is acknowledged.
Claim(s) 22, 25-30, 39, and 40 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group II, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 05/05/2026.
In the reply filed on 05/05/2026, Applicant added claim(s) 47-50. Claim 49 depends upon claim 39, and claim 50 depends upon claim 40, both claim(s) 39 and 40 are drawn to the nonelected Group II. Thus, claims 49 and 50 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group II, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 05/05/2026.
Applicant’s election without traverse of the nuclease of SEQ ID NO: 2 and RNA guide of SEQ ID NO: 5 in the reply filed on 05/05/2026 is acknowledged.
Claim(s) 1, 16, 18-19, 21 and 47-48 are under consideration.
Priority
Acknowledgement is made that this application is a 371 of PCT/US22/13375 filed 01/21/2022 and claims priority based on provisional application filed as 63/140,608 on 01/22/2021.
All claims are given the priority date of 01/22/2021.
Information Disclosure Statement
Receipt of the information disclosure statement(s) on 05/05/2026 is acknowledged. The signed and initialed PTO-1449 form(s) has/have been mailed with this action.
Specification
The disclosure is objected to because of the following informalities: On page 39, Applicant describes FIG.2 starting on line 33. Applicant recites on lines 33-34 “… following transfection with the nuclease of SEQ ID NO: 2. …”, however, in the Brief Description of the Drawings (on page 5), the drawings (on page 7), and later on in the description of FIG. 2 on page 39 and 40, SEQ ID NO: 4 is recited as the nuclease used for the experiment. It would be remedial to amend line 34 of page 39 to recite “… following transfection with the nuclease of SEQ ID NO: 4. …”.
Appropriate correction is required.
The use of the term(s)
ultramers (page 39, line 1)’;
lipofectamine (page 39, line 17);
Opti-MEM (page 39, line 17);
Illumina (page 39, line 30); and
NextSeq (page 39, line 32);
which is/are a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
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.
Section 33(a) of the America Invents Act reads as follows:
Notwithstanding any other provision of law, no patent may issue on a claim directed to or encompassing a human organism.
Claim(s) 21, 47, and 48 are rejected under 35 U.S.C. 101 and section 33(a) of the America Invents Act as being directed to or encompassing a human organism. See also Animals - Patentability, 1077 Off. Gaz. Pat. Office 24 (April 21, 1987) (indicating that human organisms are excluded from the scope of patentable subject matter under 35 U.S.C. 101).
Claim 21 does not explicitly recite “human organism”, however the instant specification discloses:
“In some aspects, the invention provides a method of introducing an insertion, deletion, or substitution into a target nucleic acid in a cell, the method comprising: (a) delivering the nuclease or the nucleic acid encoding the nuclease described herein, and the RNA guide or the nucleic acid encoding the RNA guide described herein to the cell; or (b) delivering the composition described herein to the cell. In some aspects, the cell is a eukaryotic cell. In some aspects, the cell is a prokaryotic cell. In some aspects, the cell is a human cell.”, (see page 5, lines 7-15).
“The nucleases described herein can be introduced into a variety of cells. . . In some embodiments, the cell is a human cell.”, (see page 27, lines 11 and 24).
“In one embodiment, a cell comprising a target DNA is in vitro, in vivo, or ex vivo.”, (see page 27, line 37).
“The present disclosure provides methods of in vivo expression of a nuclease in a cell,
comprising providing a polyribonucleotide encoding the nuclease to a host cell wherein the polyribonucleotide encodes the nuclease, expressing the nuclease in the cell, and obtaining the nuclease from the cell.”, (see page 29, lines 33-36).
“Embodiment 43 provides the method of any one of embodiments 22-40, wherein the cell is a human cell.”, (see page 36, lines 24-25).
Therefore, claim 21 encompasses a human cell in a human (i.e., a human organism), which is excluded from the scope of patentable subject matter.
Claim(s) 47 and 48 are rejected for being dependent upon claim 21.
Limiting claim 21 to “an isolated cell” would obviate the rejection.
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 16 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 16 recites, “A composition comprising the nuclease or the nucleic acid encoding the nuclease of claim 1.” Claim 16 depends from claim 1 and only requires the component of claim 1 to be present in the composition. Thus, claim 16 does not include all of the limitations of the claim from which it depends.
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 § 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) 1, 16, 18-19, 21, and 47-48 are rejected under 35 U.S.C. 103 as being unpatentable over Lai et al (WO 2020098772A1, published 05/22/2020; Cited on 892 Filed 02/05/2026 and in Translated form on IDS filed on 05/05/2026) in view of Doudna et al (US 2021/0324356 A1, published October 21st, 2021; effective filing date of December 16th, 2019).
Lai et al teaches Cas12j protein variants, the prototypes of guide RNA that correspond to each Cas12j variant, e.g., Cas12j.20 protein and Cas12j.20 prototype direct repeat sequence, spacers to be added onto the guide RNA, compositions of the complexes of Cas12j variants and their respective guide RNA, and cells comprising the complexes.
More specifically, Lai et al teaches Cas12j.20’s amino acid sequence (SEQ ID NO: 18), the nucleic acid that encodes the Cas12j.20 amino acid sequence (SEQ ID NO: 38), and Cas12j.20’s corresponding direct repeat sequence (SEQ ID NO: 58).
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Regarding claim 1, Lai et al teaches the amino acid sequence of Cas12j.20 (SEQ ID NO: 18), which is a nuclease with 99.8% sequence identity to SEQ ID NO: 2. Lai et al also teaches a nucleic acid encoding Cas12j.20 (SEQ ID NO: 38). See alignment below of instant SEQ ID NO: 2 and SEQ ID NO: 18 of Lai et al.
Regarding claim 16, 18 and 19, Lai et al teaches, “In a ninth aspect, the present invention further provides a composition comprising: (i) a first component selected from the group consisting of: a protein, a conjugate, a fusion protein, a nucleotide sequence encoding the protein or fusion protein of the present invention, and any combination thereof; and (ii) a second component, which is a nucleotide sequence comprising a guide RNA, or a nucleotide sequence encoding the nucleotide sequence comprising the guide RNA; Wherein, the guide RNA comprises a direct repeat sequence and a guide sequence from the 5' to the 3' direction, and the guide sequence can hybridize with the target sequence; The guide RNA is capable of forming a complex with the protein, conjugate or fusion protein described in (i). In certain embodiments, the direct repeat sequence is an isolated nucleic acid molecule as defined in the fourth aspect.”, (see paragraphs [0398] to [0403]). More specifically, “Design the template for guide RNA transcription. The structure of the transcription template is: T7 promoter + prototype repeat of Cas12j (SEQ ID NO: 41-60) + spacer (SEQ ID NO: 104). Primers were designed using Primer5. Software to ensure that the forward primer and reverse primer had at least 18 bp of overlapping sequence.”, (see paragraph [0562]; where guide sequence reads on “Spacer” see [0491]).
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Cas12j.20’s corresponding direct repeat sequence is disclosed in SEQ ID NO: 58. SEQ ID NO: 58 is 100% identical to instant SEQ ID NO: 5 (see alignment below).
Regarding claim 21, 47, and 48, Lai et al teaches, “The present invention also relates to an in vitro, ex vivo or in vivo cell or cell line or their progeny, which comprises: the protein as described in the first aspect . . . the isolated nucleic acid molecule as described in the fourth aspect, the complex as described in the fifth aspect, the isolated nucleic acid molecule as described in the sixth aspect . . . the composition as described in the ninth aspect, the composition as described in the tenth aspect, the kit or delivery composition of the present invention.”, (see paragraph [0478]).
More specifically, “In certain embodiments, the cell is a prokaryotic cell. In certain embodiments, the cell is a eukaryotic cell. In certain embodiments, the cell isa mammalian cell. In certain embodiments, the cell is a human cell. In certain embodiments, the cell is a non-human mammalian cell, such as a non-human primate, bovine, ovine, porcine, canine, monkey, rabbit, rodent (eg, rat or mouse) cell. In certain embodiments, the cell is a non-mammalian eukaryotic cell, such as a cell of a poultry bird (eg, chicken), fish, or crustacean (eg, clams, shrimp). In certain embodiments, the cell is a plant cell, e.g., a cell of a monocot or dicot plant or a cell of a cultivated plant or food crop such as cassava, corn, sorghum, soybean, wheat, oats, or rice, e.g., algae, a tree, or a production plant, fruit, or vegetable (e.g., trees such as citrus trees, nut trees; nightshade, cotton, tobacco, tomato, grape, coffee, cocoa, etc.). In certain embodiments, the cell is a stem cell or a stem cell line.”, (see paragraphs [0479] to [0481]).
Despite Lai et al teaching a nuclease with 99.8% similarity, Lai et al does not teach a nuclease comprising SEQ ID NO: 2.
Doudna et al teaches Cas12j (also known as Casϕ) diversity. Specifically, Doudna et al teaches 18 different Cas12J amino acid sequences, starting at SEQ ID NO: 109 (in Fig. 6A) and ending at SEQ ID NO: 126 (in Fig, 6R). These sequences range from 441 to 812 amino acids (see table below).
SEQ ID NO:
AA length
SEQ ID NO:
AA length
SEQ ID NO:
AA length
SEQ ID NO:
AA length
SEQ ID NO:
AA length
SEQ ID NO:
AA length
109
707
112
766
115
793
118
812
121
793
124
772
110
757
113
812
116
441
119
772
122
793
125
765
111
765
114
812
117
812
120
717
123
717
126
776
Doudna et al teaches the conserved RuvC-I, RuvC-II, and RuvC-III amino acid positions for all 18 Cas12j proteins (see Fig. 9 on sheet 24 of 108). Wherein RuvC-I contains an aspartic acid between A.A. 369 and 464 of the 18 proteins. Wherein RuvC-II contains a Glutamic acid between A.A. 567 and 678 of the 18 proteins. Wherein RuvC-III contains an Aspartic acid between A.A. 658 and 769 of the 18 proteins.
Doudna et al teaches the domain structure of a Cas12J in Fig. 19B and that the RuvC motifs are more C-terminal of the protein, see structure below.
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Therefore, it would have been obvious to try to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the nuclease (SEQ ID NO: 18) as taught by Lai et al with the teachings of Doudna et al, i.e., Cas12j proteins are highly variable outside of their conserved RuvC domains. Lai et al teaches a protein with a finite number of amino acids (i.e., SEQ ID NO: 18 with 821 amino acids). Doudna et al teaches structure that must be present for the Cas12J protein(s) (18 disclosed) to function (i.e., a conserved aspartic acid in the RuvC-I domain, a conserved glutamic acid in the RuvC-II domain, and a conserved aspartic acid in the RuvC-III domain). Additionally, Doudna et al teaches that the structure outside of the amino acid (i.e., aspartic acid in RuvC-I, glutamic acid in RuvC-II, aspartic acid in RuvC-III) can be varied greatly and that there are no reported functional domains beyond the conserved RuvCIII domain.
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When comparing SEQ ID NOs: 109 and 110 of Doudna et al, there is a highly conserved aspartic acid in the RuvC-III domain, despite an overall query match score of 40.9%, (see alignment below).
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When comparing Doudna et al’s SEQ ID NO: 109 with Lai et al’s SEQ ID NO: 18, the aspartic acid is conserved (see alignment below):
Thus, one would have had a reasonable expectation of success in varying the amino acids outside the conserved region, including position 812 of SEQ ID NO: 18 of Lai to a glycine residue and retain protein activity without loss of guide binding and target cleavage efficacy.
Accordingly, claim(s) 1, 16, 18-19, 21, and 47-48 are unpatentable over Lai et al in view of Doudna et al.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LEXUS M TATGE whose telephone number is (571)272-0061. The examiner can normally be reached Monday-Friday: 8:30am to 5:30pm.
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/L.M.T./Examiner, Art Unit 1637 /Jennifer Dunston/Supervisory Patent Examiner, Art Unit 1637
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