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 status
Claims 35, 40-41 and 51-67 are pending.
Claims 35, 41, 51-64 and 67 are examined on the merits in the present Office action.
Claims 40 and 65-66 are withdrawn.
Claims 35, 41. 51. 53-55 and 62-64 are currently amended.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 8/4/2025 has been entered.
Withdrawn rejections
The rejection of claims 35, 41, 51-56, 58-64 and 67 under 35 USC 102(a)(1) is withdrawn in light of amendments made by Applicant.
The rejection of claim 57 under 35 USC 102/103 is withdrawn in light of amendments made by Applicant.
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.
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 35, 41, 51-64 and 67 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.
Claims 35, 57 and 59-63 repetitively recite “first” or “second” wherein each adjective is used for different nucleic acid sequences, i.e., targets and sequences encoding nucleases. E.g., in claim 35, “a first nucleic acid encoding a TAL effector nuclease monomer,” “a set of second nucleic acids encoding at least a second TAL effector nuclease monomer capable of binding to a second sequence of a first… target… and another second TAL effector nuclease monomer capable of binding to a seonc sequence of a second of the… targets… forming: a first dimer with the first TAL effector nuclease monomer and the second…”. This recitation makes it unclear whether a sequence being referred to is encoding a nuclease, comprises a target sequence and how it relates to the other sequences recited prior and after. It is not clear what is being referred to in dependent claims referring to a “first” or “second” sequence. Dependent claims 41, 51-56, 58, 64 and 67 fail to recite additional limitations overcoming the indefiniteness of these claims. Their metes and bounds are thus unclear as well. Applicant may consider referring to TALEN-encoding sequences by “left-” or “right-” half talon, instead of first and second, for example.
Claim 57 recites, “…the first nucleic acid and each second nucleic acid comprise a FokI endonuclease domain.” It is not clear how a nucleic acid would comprise a protein or a portion thereof. The art-accepted understanding of a nucleic acid would not comprise a protein or portion thereof, such as a nuclease. Applicant is recommended to recite “encode”, in place of “comprise”.
Written Description
The following is a quotation of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), first paragraph:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 35, 41, 51-64 and 67 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Applicant claims a method of introducing a mutation into at least two targets by contacting a population of cells with a composition for expressing TALEN (TAL effector nuclease) pairs wherein the composition comprises a nucleic acid that encodes a TALEN that binds to a sequence that is conserved across each of the targets. The composition also comprises a set of nucleic acids encoding one or more TALENs which bind to a different sequence than the conserved sequence and to each of the other sequences, each completing a dimer with the nucleases bound to a conserved sequence. Claims dependent on claim 25 specify that the cell of claim 35 is a plant cell, wherein mutations are introduced with the first and second dimer (claim 51), identifying a region of homology among the targets, designing the first TAL effector nuclease monomer to target the region and synthesizing the first nucleic acid (claim 53), aligning the genomic sequences of the targets (claim 54), the first sequence of claim 35 is a 100% conserved sequence of the targets within at least two genes (claim 55), the spacer sequence is about 15-18 nucleotides in length (claim 56), the first nucleic acid and each second encode a Fok1 endonuclease domain (claim 57), the first and the set of second nucleic acids are in a single vector (claim 58), the first nucleic acid is an mRNA in a plasmid (claim 59), each second nucleic acid is an mRNA in a plasmid (claims 60 and 61), the set of second nucleic acids comprises at least three nucleic acids (claims 62-63), the targets are within gene members of a single gene family (claim 64), the plant with the mutations produces oil with increased oleic acid content and at least one mutation is induced by a rare cutting endonuclease capable of binding a nucleic acid sequence from SEQ ID NO: 27-34 or a functional variant thereof (claim 67).
Applicant claims a method for generating a soybean plant comprising a mutation reducing expression of a FAD2-1A or FAD2-1B gene. The method comprises contacting soybean cells with a functional FAD2-1A and FAD2-1B gene with one or more sequences encoding a rare cutting endonuclease capable of binding to a nucleic acid sequence from SEQ ID NO:27-34 or a functional variant thereof and wherein the target sequence comprises SEQ ID NO: 20-22 or 25-26 or a function variant thereof. The method comprises selecting a cell in which expression of the FAS2-1A gene or FAD2-1B gene has been reduced by the rare cutting endonuclease and regenerating the cell into a soybean plant (claim 41).
Applicant describes transforming soybean protoplasts to express TALEN pairs SEQ ID NO: 4-19 targeting FAD3A, FAD3B and FAD3C genes (SEQ ID NO: 1-3) ([0075]; Table 3); TALEN pairs SEQ ID NO: 27-36 targeting genes FAD2-1A and FAD2-1B ([0079]; Table 4). Applicant describes transforming a soybean plant to express a combination of three half-TALENs with the highest activity for FAD3A, FAD3B and FAD3C, achieving nuclease activities for each of the targets (measured by observation of NHEJ) [0076]. Applicant describes verifying that TALENs created mutations at target sites in two or more FAD3A/B/C, with examples of mutant alleles including SEQ ID NO:40-44 [0077]. Applicant describes verifying that TALENs created mutations at target sites in one or more FAD2-1A/B, with examples of mutant alleles including SEQ ID NO:37-39 [0080].
Soybean seed which were homozygously mutant in two or more FAD3A/B/C [0078] and one or more FAD2-1A/B were analyzed for fatty acid composition [0081]. Applicant describes producing plants with knock out activity of one or more FAD2 and FAD3 genes, including plants with 2-5 genes knocked out [0082]. Applicant describes an increase in oleic oil content in plants with genes knocked out [0083].
Applicant does not describe the genus of methods as broadly claimed. Applicant has not described a method of introducing a mutation into a population of cells other than a soybean plant, specifically to FAD2 and FAD3 genes. Applicant has not described a representative number of species nor a structure function relationship that would allow one of ordinary skill in the art to envision which members of the genus of “functional variant” of target sequences and sequences encoding a TALEN would result in a mutation that reduces expression of at least a FAD2-1A or FAD2-1B gene. The described embodiments are not representative of the breadth of the claimed genus such that one of ordinary skill in the art would be able to envision which members of the claimed genus possess the claimed function. For example, Applicant describes FAD2-1A and FAD2-1B targeted with TALENS SEQ ID NO: 35 and SEQ ID NO: 36 did not have NHEJ (Table 4). Given the breadth of the genera encompassed by the claims, the described species are not sufficiently representative.
Given limited guidance supplied by Applicant, the breadth of the claims and the nature of the invention, as well as the unpredictability in the art, Applicant has not satisfied the written description requirement across the full scope of its claims.
Conclusion
Claims 35, 41, 51-64 and 67 remain rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DAVID R BYRNES whose telephone number is (571)270-3935. The examiner can normally be reached 9:00 - 5:00 M-F.
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/DAVID R BYRNES/Examiner, Art Unit 1662