DETAILED ACTION
Applicant's submission filed on January 5, 2026 has been entered.
Claim 1-114 are cancelled.
Claims 115-130 are pending.
Claim 115, 116 and 128 are currently amended.
Claim 117 is withdrawn, currently amended.
Claims 118-127 are withdrawn.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
All previous objections and rejections not set forth below have been withdrawn.
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 .
Withdrawn Claim Rejections
The rejection of claims 115-116 and 128-130 under 35 U.S.C. 103 as being unpatentable over Campbell et al. (U.S. Patent Application Publication No. 2018/0245090, published Aug. 30, 2018) in view of Prigge et al. (Production of Haploids and Doubled Haploids in Maize. Methods Mol. Biol. 2012:877:161-72) and Cigan et al. (U.S. Patent Application Publication No. 2020/0332305, published Oct. 22, 2020), and further in view of McBride et al. (U.S. Patent No. 5,576,198, issued Nov. 19, 1996) is withdrawn in light of the claim amendments.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph 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 the first paragraph of pre-AIA 35 U.S.C. 112:
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 115-116 and 128-130 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 115 as currently amended is drawn to a method of editing maize genomic DNA, comprising:
a) introducing at least one Genome Editing Component (GEC) into a chloroplast genome of a maize haploid inducer line that comprises an ig1 haploid inducer to produce a first maize plant that comprises the at least one GEC and the haploid inducer,
wherein the at least one GEC comprises at least one recombinase or at least one endonuclease operably linked to a transfer peptide that transfers the at least one recombinase or the at least one endonuclease from the chloroplast to the nucleus;
b) providing a second maize plant, wherein the second maize plant comprises the maize plant genomic DNA which is to be edited;
c) crossing the second maize plant with the first maize plant; and
d) selecting at least one haploid progeny produced by the cross of step (c) wherein the haploid progeny comprises the genome of the second maize plant but lacks the genome of the first maize plant, and wherein the genome of the haploid progeny comprises at least one targeted genome modification.
Claim 116 as currently amended is drawn to the method of claim 115, wherein the at least one GEC comprises at least one recombinase.
Claim 128 as currently amended is drawn to the method of claim 115, wherein the endonuclease is Cpf1.
Claim 129 as currently amended is drawn to the method of claim 115, wherein the GEC is introduced into the chloroplast genome of the maize haploid inducer line by crossing a maize plant that comprises the ig1 inducer with a maize plant that comprises the GEC in the chloroplast genome.
Claim 130 is drawn to the method of claim 129, wherein the haploid progeny comprises the maternal mitochondrial and plastid genomes.
The specification in Example 4 describes a method of modifying a plant genome using a chloroplast genome as a GEC carrier chromosome (pages 43-44). With respect to a transfer peptide that transfers the at least one recombinase or the at least one endonuclease from the chloroplast to the nucleus, the specification refers to a single species, a peptide that is a portion of the whirly protein, with reference being made to Isemer et al. (Recombinant Whirly1 translocates from transplastomic chloroplasts to the nucleus. FEBS Lett. 2012 Jan 2;586(1):85-8. Epub 2011 Dec 3).
Isemer et al. teach that a recombinant HA-tagged Whirly1 protein expressed from a construct introduced into the plastid genome of a tobacco plant cell could be detected in both the chloroplasts and nucleus of the same cell, indicating the translocation of the HA-tagged Whirly1 protein from the chloroplast to the nucleus. Isemer et al. also teach that only a few proteins are known to exhibit dual localization in an organelle and in the nucleus of a cell (page 85 column 1 second paragraph).
Neither the specification nor Isemer et al. describe the structure of a peptide that is a portion of the whirly protein wherein the peptide functions to transfer an operably linked protein from the chloroplast to the nucleus of a plant cell. Further, neither the specification nor the prior art describe the structure of other peptides that function to transfer an operably linked protein from the chloroplast to the nucleus of a plant cell.
In order to satisfy the written description requirement for genus claims, the specification can disclose a representative number of species of the claimed genus by reduction to practice, drawings, or complete structural description; alternatively the specification may disclose some correlation between structure and function that is common to the members of the genus.
In the instant case, given the breadth of the claims with respect to the required element of a transfer peptide of any unspecified structure from any unspecified source that can function to transfer a protein from the chloroplast of a cell to the nucleus of a cell, given the absence of any description of any transfer peptide that can perform this function, and given the absence of any disclosure of the structural features unique to the genus of peptides that are correlated with their ability to transfer a protein from the chloroplast of a cell to the nucleus of a cell, the written description requirement is not satisfied.
Claims 115-116 and 128-130 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Claim 115 as currently amended is drawn to a method of editing maize genomic DNA, comprising:
a) introducing at least one Genome Editing Component (GEC) into a chloroplast genome of a maize haploid inducer line that comprises an ig1 haploid inducer to produce a first maize plant that comprises the at least one GEC and the haploid inducer,
wherein the at least one GEC comprises at least one recombinase or at least one endonuclease operably linked to a transfer peptide that transfers the at least one recombinase or the at least one endonuclease from the chloroplast to the nucleus;
b) providing a second maize plant, wherein the second maize plant comprises the maize plant genomic DNA which is to be edited;
c) crossing the second maize plant with the first maize plant; and
d) selecting at least one haploid progeny produced by the cross of step (c) wherein the haploid progeny comprises the genome of the second maize plant but lacks the genome of the first maize plant, and wherein the genome of the haploid progeny comprises at least one targeted genome modification.
Claim 116 as currently amended is drawn to the method of claim 115, wherein the at least one GEC comprises at least one recombinase.
Claim 128 as currently amended is drawn to the method of claim 115, wherein the endonuclease is Cpf1.
Claim 129 as currently amended is drawn to the method of claim 115, wherein the GEC is introduced into the chloroplast genome of the maize haploid inducer line by crossing a maize plant that comprises the ig1 inducer with a maize plant that comprises the GEC in the chloroplast genome.
Claim 130 is drawn to the method of claim 129, wherein the haploid progeny comprises the maternal mitochondrial and plastid genomes.
The specification in Example 4 discloses a method of modifying a plant genome using a chloroplast genome as a GEC carrier chromosome (pages 43-44). With respect to a transfer peptide that transfers the at least one recombinase or the at least one endonuclease from the chloroplast to the nucleus, the specification refers to a single peptide, a peptide that is a portion of the whirly protein, with reference being made to Isemer et al. (Recombinant Whirly1 translocates from transplastomic chloroplasts to the nucleus. FEBS Lett. 2012 Jan 2;586(1):85-8. Epub 2011 Dec 3).
Isemer et al. teach that a recombinant HA-tagged Whirly1 protein expressed from a construct introduced into the plastid genome of a tobacco plant cell could be detected in both the chloroplasts and nucleus of the same cell, indicating the translocation of the HA-tagged Whirly1 protein from the chloroplast to the nucleus. Isemer et al. also teach that only a few proteins are known to exhibit dual localization in an organelle and in the nucleus of a cell (page 85 column 1 second paragraph).
Neither the specification nor Isemer et al. disclose any particular peptide that is a portion of the whirly protein wherein the peptide functions to transfer an operably linked protein from the chloroplast to the nucleus of a plant cell. Further, neither the specification nor the prior art disclose other peptides that function to transfer an operably linked protein from the chloroplast to the nucleus of a plant cell.
The claimed invention is not enabled because the claimed methods rely on the availability of a transfer peptide that can transfer a protein such as a recombinase or an endonuclease from the chloroplast of a cell to the nucleus of a cell, which transfer peptide is not disclosed in the specification, and was not known in the art at the time of filing. While the phenomenon of dual targeted proteins is generally recognized in the art, the art also acknowledges that dual targeting of different proteins may occur as a consequence of a variety of different mechanisms that are not fully understood.
See, for example, Nevarez et al. (Mechanism of Dual Targeting of the Phytochrome Signaling Component HEMERA/pTAC12 to Plastids and the Nucleus. Plant Physiol. 2017 Apr;173(4):1953-1966. Epub 2017 Feb 23), who teach that dual distribution of a protein can be achieved by two general strategies, one that involves the production of two protein variants that differ in subcellular targeting signals due to alternative transcription or translation initiation sites, and another that involves the production of a single protein that can be targeted to two subcellular compartments (page 1961 column 2 last paragraph). Nevarez et al. also teach that the best recognized mechanism for targeting a single protein to the nucleus and to an organelle is the presence of two different targeting signals, a nuclear targeting signal and an organellar targeting signal (page 1962 column 1 first full paragraph). Nevarez et al. additionally teach retrograde protein translocation as an alternative mechanism for targeting a single protein to the nucleus and to an organelle, with Whirly1 (Why1) and HEMERA/pTAC12 (HMR) being exemplary of proteins that may be targeted in this manner. Nevarez et al. teach that while the mechanism of retrograde protein translocation is still largely unknown, at least three possible pathways have been proposed, an unidentified translocon or secretory pathway, leakage due to organellar damage or autophagy, and translocation through physical connections between the subcellular compartments such as stromules (page 1962 column 1 first full paragraph through column 2 first full paragraph).
In the instant case the specification does not provide sufficient guidance with respect to how to make and use a transfer peptide that can transfer a protein such as a recombinase or an endonuclease from the chloroplast of a cell to the nucleus of a cell. Such guidance is necessary because although the phenomenon of dual targeted proteins is generally recognized in the art, the art also acknowledges that dual targeting of different proteins may occur as a consequence of a variety of different mechanisms that are not fully understood, and the type of transfer peptides required to practice the claimed methods were not known and used in in the art at the time of filing. Absent such guidance one skilled in the art would have to identify potential transfer peptides in proteins that are targeted to both the nucleus and the chloroplast, and then validate the peptides to determine which peptides, if any, function as desired. Such a trial and error approach to practicing the claimed invention would constitute undue experimentation
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
Remarks
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CYNTHIA E COLLINS whose telephone number is (571)272-0794. The examiner can normally be reached M-F 8:30 am - 5:00 pm.
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/CYNTHIA E COLLINS/Primary Examiner, Art Unit 1662
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