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 .
Claims 17 and 21-23 are pending and examined herein on the merits.
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 17 and 21-23 remain rejected under 35 U.S.C. 103 as being unpatentable over Marton et al (2010 Plant Physiology 154:1079-1087), in view of in view of Liang et al (2014 Journal of Genetics and Genomics 41:63-68, available online 12/14/2013).
The claims are drawn to a method for conducting site-directed modification to a target fragment of a target gene in a whole plant, comprising transiently expressing a sequence-specific nuclease in said plant, wherein said sequence-specific nuclease targets and cleaves said target fragment wherein site-directed modification is achieved via the self DNA repairing of said plant, wherein the method is for making a transgene-free mutant plant wherein the function of the target gene is lost and the genome of the plant is free of integrated exogenous genes and wherein the plant is maize and the sequence-specific nuclease is CRISPR/Cas9 and the target gene is ZmIPK wherein the target fragment is SEQ ID NO:6 and the modification is an insertion of SEQ ID NO:7, wherein the plant part for delivery of the nuclease is selected from pollen tube, inflorescence, shoot apex, or ovary and wherein the solution is dipped or injected depending on tissue type.
Marton et al teach the non-transgenic modification of genomes in plant cells, demonstrating that zinc finger nucleases can be transiently introduced using viral vectors thereby modifying the genome without integrating the genetic material that introduces the zinc finger nuclease. Specifically, Marton et al teach the modification of a GUS gene that was introduced into tobacco and petunia cells to show that genome modification was a success wherein the modification was an insertion or replacement (see figure 5, for example), wherein the repair was a self DNA repair mechanism (see Figure 4, and discussion), wherein the zinc finger nuclease has a target site binding domain and a domain that recognizes Fok I (see page 1080, 3rd paragraph, for example), wherein the zinc finger nuclease was delivered transiently by infiltrating (injecting) the underside of a leaf with solution containing Agrobacterium (see Materials and Methods “Viral Infection and Production of Target Plantlets”) wherein the viral infection and selection was achieved without selection pressure (see pages 1082-1083, for example). Marton et al also teach the transient infection of developing plant parts (which would include the shoot apex and inflorescence) wherein various plant tissues can be targeted (see last paragraph on page 1080 to first paragraph of page 1081, for example).
Marton et al teach that the aim of their invention is to eliminate the classification of modified plants as transgenic plants (wherein there are no exogenous genes present in the genome, see page 1084) because non-transient methods are likely to result in being classified as transgenic plants (see page 1084).
Marton et al do not teach the loss of function of the target gene nor the use of CRISPR-Cas.
Liang et al teach the targeting of the maize IPK gene eliminating function using CRISPR/Cas9 wherein the target site encompasses instantly claimed SEQ ID NO:6 and wherein the U3 promoter is used(see Figure 3 part B, WT line) and show that the system is interchangeable with Zinc Finger nucleases and would be preferred because of easy cloning and multiplex genome editing (see top of page 67).
Given the state of the art at the time of filing and the disclosures of Marton et al and Liang et al, it would have been obvious to one of ordinary skill in the art to modify the system taught by Marton et al designed for non-transgenic modification using CRISPR/Cas9 as taught by Liang et al given the advantages of CRISPR/Cas9 taught by Liang et al to target eliminating the IPK gene. It is further noted that zinc finger nucleases and CRISPR-Cas are both nuclease tools used for genome target modification. Both may be used for the same purpose, but in the instant case Liang et al teach that CRISPR-Cas is preferred.
Response to Arguments
Applicant's arguments filed 10/14/2025 have been fully considered but they are not persuasive.
Applicant’s urge multiple differences between the current claims and Marton et al, (see pages 4 of Response).
This is not persuasive because Marton isn’t cited in isolation, but rather in combination with Liang et al, and it is Liang et al that provides the motivation to substitute CRISPR-Cas for Zinc Finger systems such as that taught in Marton et al.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Applicant urges that there is no disclosure that teaches guide RNAs and Cas9 expression constructs need to be transformed on a single DNA plasmid as recited in claim 17 (see page 5 of response).
This is not persuasive because claim 17 does not require the argued limitation. The claim uses comprising language which is open as well as “capable” language which is similarly open such that multiple constructs and separate plasmids would still be encompassed by the claims as currently written.
No claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/BRENT T PAGE/Primary Examiner, Art Unit 1663