DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Claim Status
Claims 2, 5-7, 14 are pending.
Claim 14 is currently amended.
Claims 2, 5-7, 14 are examined on the merits.
Response to Arguments - Claim Objections
The amendments filed in the claim set filed 11 December 2025 has overcome the objection.
Response to Arguments - Indefiniteness
The amendments filed in the claim set filed 11 December 2025 has overcome the rejection.
Claim Rejections - 35 USC § 112
Lack of 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.
Claims 2 and 5-7 remain rejected and claim 14 is 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. Note: claim 14 has been added to the rejection due to amendments made. Previously, claim 14 was depending from canceled claim 1 and recited tobacco plant protoplast, thus it would have been improper to include it in the written description rejection.
The claims are broadly drawn to methods of methods comprising delivering a Cas9 endonuclease, crRNA, and a tracrRNA to a monocot protoplast to generate a double-strand break.
There is not clear contemplation of the claimed scope. All of the Examples in the instant application are written in the present tense suggesting that the examples are all prophetic and were not reduced to practice. Also, the example (Example 3) from the provisional application (screen capture below) does not recite anything related to monocots. So even prophetic examples do not contemplate the claimed scope. The originally filed claims do recite monocot and monocotyledonous species in claims 8-9 (screen capture below), but nowhere recite protoplast.
These descriptions are insufficient, because they fail to demonstrate clear contemplation of the claimed scope, modification of monocot protoplast.
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Response to Arguments - Lack of Written Description
The rejection in question is not a lack of enablement rejection. This is a lack of written description rejection. The rejection has been made, because it is not clear that Applicant had contemplated the claimed scope at the time of filing. Thus, a person of ordinary skill would not have recognized that Applicant was in position of the claimed invention at the time of filing. The Examiner is not contending that the instant disclosure and the prior art collectively do not enable the claimed invention. To the contrary, the Examiner contends that the prior art alone enables the claimed invention. This is an essential part of the obviousness rejection below.
Applicant's arguments filed 11 December 2025 have been fully considered but they are not persuasive.
Applicant urges that the written description requirement is satisfied and points to the sections indicated in screen capture below:
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This is not persuasive, because while there is generic contemplation to practice the methods in protoplasts and generic contemplation to practice the claimed method in monocots, there is no contemplation to practice the claimed method in monocotyledonous protoplasts. In fact, the specific contemplation to practice the methods in protoplasts are only in dicotyledonous species (Examples 3-4). Thus, a person of ordinary skill would not have recognized that Applicant was in position of the claimed invention at the time of filing.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
Claims 2 and 5-7 remain rejected under pre-AIA 35 U.S.C. 103(a) Lyznik et al (US 20090133152 A1) and further in view of Zhang (US 8697359).
Lyznik et al teach genome modification of monocot cells and teach that transformation can be carried out in protoplasts including maize protoplasts (paragraphs 88, 157, 160). They teach that the modification is carried out by using a site-directed nuclease to create a double strand-break (claims).
Lyznik et al do not teach to use the Cas9 endonuclease, tracrRNA, and crRNA to function as a targeting endonuclease.
In the provisional applications, Zhang teaches use of the CRISPR/Cas9 system (Cas9 endonuclease, tracrRNA, and crRNA) to generate targeted double-strand breaks in a genome to be modified (see entire document). They also contemplate that plants could be modified with the CRISPR/Cas9 system (paragraph 79).
At the time of filing, it would have been obvious and within one of ordinary skill in the art to use the double-strand break-inducing enzyme system of Zhang (CRISPR/Cas9) in the methods of Lyznik et al. A person of ordinary skill in the art, would have been motivated to modify the methods of Lyznik as Lyznik indicates that different endonucleases can be used to generate the double-strand break (see claims 12 and 34). Thus, a substitution of one endonuclease for another is contemplated by Lyznik. Accordingly, claims 2 and 5-7 remain rejected as being obvious over Lyznik further in view of Zhang.
Claim Rejections - 35 USC § 103
Claim 14 remains rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Lyznik et al (US 20090133152 A1) and Zhang (US 8697359) and further in view of Wang et al 2008 (RNA 14: p.903-913).
Lyznik et al teach genome modification of monocot cells and teach that transformation can be carried out in protoplasts including maize protoplasts (paragraphs 88, 157, 160). They teach that the modification is carried out by using a site-directed nuclease to create a double strand-break (claims).
Lyznik et al do not teach to use the Cas9 endonuclease, tracrRNA, and crRNA to function as a targeting endonuclease. Nor do they teach using the claimed RNA Pol III promoters to express the guide endonuclease.
In the provisional applications, Zhang teaches use of the CRISPR/Cas9 system (Cas9 endonuclease, tracrRNA, and crRNA) to generate targeted double-strand breaks in a genome to be modified (see entire document). They also contemplate that plants could be modified with the CRISPR/Cas9 system (paragraph 79).
Wang teaches Pol III promoter to express small RNAs in plants. The promoters include AtU6-20.
At the time of filing, it would have been obvious and within one of ordinary skill in the art to use the double-strand break-inducing enzyme system of Zhang (CRISPR/Cas9) in the methods of Lyznik et al. A person of ordinary skill in the art, would have been motivated to modify the methods of Lyznik as Lyznik indicates that different endonucleases can be used to generate the double-strand break (see claims 12 and 34). Thus, a substitution of one endonuclease for another is contemplated by Lyznik. Moreover, a person of ordinary skill in the art would have been motivated to practice the methods in dicots (as contemplated by Lyznik) including in soybean (one of the most agronomically important species) or tobacco (a species that has long been used in labs for biotechnology given the ease by which it cultured and transformed. Still further, a person of ordinary skill in the art would have been motivated to use the AtU6-20 and At7SL promoters of Wang to express the crRNA and tracrRNA as they have been proven to efficiently express small RNA molecules. Accordingly, claim 14 is rejected as being obvious over Lyznik further in view of Zhang and Wang.
Response to Arguments - Claim Rejections - 35 USC § 103
Applicant's arguments filed 11 December 2025 have been fully considered but they are not persuasive.
The Examiner would like the make the PTAB decision for the parent case 14/629,859 (Ex parte Voytas et al. Application 14/629,859 (PTAB June 24, 2021)) of record as many issues regarding obviousness of the instant invention parallel those discussed in Ex parte Voytas. In particular, the decision found that that Zhang in view of Klimyuk provided a reasonable expectation of success in modifying a plant cell using the CRISPR/Cas9 system and that this conclusion was made in light of Applicant’s (Appellant’s) arguments regarding the differences between the CRISPR/Cas system and other genome editing technologies such as ZFNs and TALENs. The Examiner questions why Applicant argues this point again in the paragraphs spanning pages 3-4 of the Remarks filed 11 December 2025 when the PTAB has already found it unpersuasive.
Applicant also urges that Wang does not teach anything about the CRISPR/Cas system.
This argument is not persuasive, because Wang teaches use of the AtU6-20 and At7SL promoters to transcribe short RNAs in a plant cell. A person of ordinary skill in the art would have recognized crRNAs and tracrRNAs as short RNAs and thus would have viewed AtU6-20 and At7SL promoters as a known means to transcribe short RNAs in a plant cell.
Applicant is also reminded of the following when responding the instant obviousness rejection:
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 is reminded that “A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton.” KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385, 1397 (2007). “[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle.” Id. Office personnel may also take into account “the inferences and creative steps that a person of ordinary skill in the art would employ.” Id. At 82 USPQ2d at 1396. See MPEP Section 2141.03.
Conclusion
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 extension fee 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.
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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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amjad Abraham can be reached on 571-270-7058. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MATTHEW R KEOGH/Primary Examiner, Art Unit 1663
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