DETAILED ACTION
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 .
This is a Final Office Action in response to amendment filed on 7/9/2026.
Election/Restriction
The Office acknowledges the receipt of Applicant’s restriction election filed December 16, 2025. Applicant elects Group I, encompassing claims 1-5, 7-9, 57, 59, and 60. Because no traverse is presented, this election is treated as election without traverse. Groups 2 and 3 are pending. Groups 2 and 3 are withdrawn from examination. Group 1, claims 1-5, 7-9, 57, 59, and 60 drawn to a method of producing a doubled haploid plant comprising providing a plant comprising an introduced genetic chromosome doubling polypeptide and crossing with a second plant, wherein the polypeptide induces chromosome doubling of an egg cell are examined in the instant application.
The restriction is made FINAL .
Claim Status
Claims 1-5, 7-9, 15-17, 22-24, 26-28, 59, and 60 are pending.
Claims 1-5, 7-9, 59, and 60 are examined on the merits.
Claims 7-9, 15-17, 22-24, and 26-28 are withdrawn as a result of Restriction.
Claims 1, 15, 22, and 60 are amended.
Claim 57 is canceled.
Response to Amendment
The rejection of Claim 60 rejected under 35 U.S.C. 112(b) is withdrawn in view of amendment to the claims.
The rejection of Claims 1-5, 7-9, 59, and 60 rejected under 35 U.S.C. 112(a) is maintained and modified in view of amendment to the claims.
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.
Written Descriptions
Claims 1-5, 7-9, 59, and 60 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.
The Federal Circuit has clarified the application of the written description requirement. The court stated that a written description of an invention "requires a precise definition, such as by structure, formula, [or] chemical name, of the claimed subject matter sufficient to distinguish it from other materials". University of California v. Eli Lilly and Co., 119 F.3d 1559, 1568; 43 USPQ2d 1398, 1406 (Fed. Cir. 1997). The court also concluded that "naming a type of material generally known to exist, in the absence of knowledge as to what that material consists of, is not description of that material". Id. Further, the court held that to adequately describe a claimed genus, Patent Owner must describe a representative number of the species of the claimed genus, and that one of skill in the art should be able to "visualize or recognize the identity of the members of the genus". Id.
Claims 1 and the dependent claims 2-5, 7- 9, and 59-60 regards the “amino acid sequence having at least 95% identity to SEQ ID NO:23”, a genetic chromosome doubling polypeptide. SEQ ID NO:23 is ZM-CYCD2-related polypeptide, a maize cyclin delta-2-like protein (paragraph 0184). The claimed method requires the ZM-CYCD2-related polypeptide to endow the functional property of inducing chromosome doubling of an egg cell of a second plant when crossed.
The scope of the claimed genetic chromosome doubling polypeptide is broad, because it encompasses any polypeptide having at least 95% amino acid sequence identity to maize cyclin delta-2-like protein (SEQ ID NO:23).
In contrast to the broad scope, the Specification has described the cyclin gene-based genetic chromosome doubling factor, ZM-CYCD2 (DNA SEQ ID NO:17) encoding the cyclin delta-2-linke protein (protein SEQ ID NO:23), implemented in transformed haploid inducer lines as an introduced genetic chromosome doubling factor involving ZM-CYCD2 and/or limited variants thereof as having chromosome-doubling activity. For example, the specification describes that genetic chromosome doubling of a parthenogenic haploid embryos is achieved by providing to an egg cell the activity of a cyclin gene dpzm07g031470.1.1 encoding a cyclin delta-2-like protein, wherein activity during female gametogenesis provides chromosome doubling in vivo to yield a diploidized embryo comprising only maternal chromosomes (example 4C, paragraph 0184-0185) demonstrating introduction of egg-cell chromosome doubling and production of doubled haploid plant.
However, the Specification does not describe any additional polypeptide having at least 95% identity to SEQ ID NO: 23 that was shown to induce chromosome doubling of an egg cell in the claimed method. The specification therefore provides a working description of the exact SEQ ID NO: 23 species, but does not provide a representative number of additional species across the claimed ≥95% identity functional genus.
The Specification fails to sufficiently describe the necessary structural features that must be retained by ZM-CYCD2 related polypeptides to establish a structure-function relationship with respect to the specific function of inducing the egg cell chromosome doubling.
Firstly, the Specification has not described the essential structural features that must be shared by the members of the broad genus of ≥95% identity ZM-CYCD2 related polypeptides to achieve chromosome-doubling activity. Although cyclin D proteins share common cyclin domains, closely related cyclin D family members and variants are known to differ in regulatory roles, expression patterns, and biological function. The specification does not identify which structural features of ZM-CYCD2 proteins are responsible for the claimed chromosome-doubling activity. For example, Menges (Margit Menges et. al., Plant Physiology, Vol. 145, pp. 1558–1576, 2007) reports that Arabidopsis has 10 CYCD genes in seven subgroups, and discusses conservation/diversification across higher plants (page 1558). Godinez-Palma (Silvia K. Godínez-Palma, et. al., Journal of Experimental Botany, Vol. 64, No. 18, pp. 5661–5671, 2013) states “maize cells contain 17 different genes coding for D-type cyclins” maize has very close D2-type paralogs, Godinez-Palma notes cycD2:2 (a or b) are ~94% identical, yet still treated as distinct gene products/variants in maize (page 5562). Cyclin D proteins, including maize cyclin delta-2-like protein, are known cell-cycle regulators whose biological activity depends on precise interactions with CDKs and other regulatory factors, Godinez-Palma (page 5661) discloses “Binding to cyclin D2;2 was detectable at all germination times, forming a complex with kinase activity”. Cyclin-D function is not defined merely by overall “cyclin-like” similarity; rather, specific interaction determinants (such as the LxCxE-type pocket-protein interaction motif) can be required for RBR interaction, illustration the limited sequence change can disrupt key functional interactions even when overall identity remain high, Horvath (Beatrix M Horvath, et. al., 2;36(9):1261-1278, 2017) (page 1261 and 1273). Sabelli (Paolo A. Sabelli et. al., PNAS vol. 102 no. 37, pp13005-13012, 2005) discloses maize RBR family interaction networks shows that mutagenesis abolishes interactions, their data indicates interactions abolished by mutation of LxCxE motif, illustrating that LxCxE motif can be determinative for binding/function in RBR-linked cell-cycle regulation (page 13005, 13009). Boniotti (M B Boniotti et. al., Plant Journal, 28(3):341-350, 2001) also support that CDK/cyclin complexes bind and phosphorylate plant RBR proteins across species (maize included), reinforcing that RBR-axis interactions are central and thus structural determinants of those interactions’ mater (page 341, summary).
Secondly, the Specification has not described how the unspecified amino acid substitutions, deletions, or insertions withing the ≥95% identity range would impact the function of ZM-CYCD2-related protein. Such sequence changes may reduce, abolish, or otherwise alter cyclin-dependent kinase interactions or regulatory specificity, thereby affecting cell-cycle control and developmental outcomes. Without disclosure addressing how such variations affect function. It is unclear which members of the claimed genus would retain the claimed chromosome-doubling activity. A study on leaf-petal allometry in Arabidopsis fine-mapped shows that CYCD2;1 varies in nature and is connected to G1 control/cell division rate: among the genes studied, a unique variant of the CYCD2;1 gene, which regulates the pace of cell division in the growth zones of the plant (meristems), was found exclusively in the Hi-0 strain of Arabidopsis. This unique gene variant is a likely reason why Hi-0 shows distinct growth characteristics (such as leaf/petal size or shape) Li(Xin Li, et. al., BMC Plant Biology, 20:547, pp1-11, 2020) (page 6). Multiple plant papers report that the same gene expressing CYCD2:1 cDNA can yield an aberrantly spliced mRNA that lacks part of the conserved cyclin box, and confirmed the cyclin box is essential for CDKA binding and gene function. Sanz (Luis Sanz et. al., Plant Cell. 23(2):641–660, 2011) (page 647).
These references do not establish that every sequence having at lease 95% identity to SEQ ID NO: 23 lacks activity. Rather, they demonstrate that cyclin function depends upon particular structural and interaction determinants and that overall classification as a highly similar D-type cyclin does not, by itself, establish retention of the specific egg-cell chromosome-doubling function required by the claims.
SEQ ID NO: 23 contains 355 amino acids. A 95% identity threshold permits approximately 17 amino-acid differences, depending upon the alignment methodology and treatment of insertions and deletions. Those difference may occur at numerous combinations of positions and may affect protein folding, stability, CDK interaction, RBR interaction, localization, regulation, or activity in the relevant reproductive cell.
The specification does not identity: which amino-acid positions may be altered while retaining the claimed function; which amino-acid positions or motifs must be preserve; which substitutions are conservative or tolerated in the context of the claimed activity; whether insertions or deletions are permitted at particular locations; a structure-function relationship correlating sequence variation with egg-cell chromosome-doubling activity; or any other structural criterion by which a skilled artisan could distinguish functional members of the claimed genus from nonfunctional member.
Although the claim’s functional language excludes variants that do not induce chromosome doubling, that functional limitation does not itself provide written-description support for the members that do perform the function. Here, the specification identifies only SEQ ID NO:23 and does not disclose additional functional variants or structural features correlated with the claimed phenotype.
Accordingly, the disclosure does not provide either a representative number of species within the claimed functional genus or common structural features correlated with the claimed egg-cell chromosome-doubling function sufficient to allow a person of ordinary skill in the art to visualize or recognize the members of that genus.
Scope of Enablement
Claims 1-5, 7-9, 59, and 60 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specifications, while being enabling for maize maternal haploid induction using MTL/MATL haploid inducer lines transformed to express doubling factor ZmCYCD2 (SEQ ID NO:23); does not reasonably provide enablement for the full scope of the claimed method, including use of a genetic chromosome doubling polypeptide having at least 95% sequence identity to SEQ ID NO: 23. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
An “analysis of whether a particular claim is supported by the disclosure in an application requires a determination of whether that disclosure, when filed, contained sufficient information regarding the subject matter of the claims as to enable one skilled in the pertinent art to make and use the claimed invention.” MPEP 2164.01. “A conclusion of lack of enablement means that. . . the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention [i.e. commensurate scope] without undue experimentation.” In re Wright, 999 F.2d 1557,1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993); MPEP 2164.01.
In In re Wands, 858 F.2d 731,8 USPQ2d 1400 (Fed. Cir. 1988), several factors implicated in determination of whether a disclosure satisfies the enablement requirement and whether any necessary experimentation is “undue” are identified. These factors include, but are not limited to:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. In re Wands, 858 F.2d 731,737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988). No single factor is independently determinative of enablement; rather “[i]t is improper to conclude that a disclosure is not enabling based on an analysis of only one of the above factors while ignoring one or more of the others.” MPEP 2164.01. Likewise, all factors may not be relevant to the enablement analysis of any individual claim.
Claim 57 has been canceled. Accordingly, the portion of the previous enablement rejection directed specifically to crosses in which the first plant and the second plant are of different species or genera is withdrawn and is not maintained in this action.
Claims 1 and the dependent claims 2-5, 7- 9 and 59-60 regards the “amino acid sequence having at least 95% identity to SEQ ID NO:23”, a genetic chromosome doubling polypeptide.
Here, the claims recite a method requiring a first maize plant comprising a broad genus of genetic chromosome doubling polypeptide. The claimed method requires the genetic chromosome doubling polypeptide to endow a property of inducing chromosome doubling of an egg cell of the second plant in the absence of an exogenously applied chemical or biochemical chromosome doubling agent, and obtaining a diploidized embryo comprising a pair of chromosomes inherited from the second plant and not comprising the introduced genetic chromosome doubling polypeptide, followed by regeneration of a doubled haploid platelet or plant.
The scope of the broad genus of genetic chromosome doubling polypeptide is broad, because it encompasses any polypeptide having at least ≥95% sequence identity to SEQ ID NO:23, and the polypeptide is capable of performing the specific functional requirement recited in the claims (i.e., inducing chromosome doubling of an egg cell in vivo in the claimed crossing context, without chemical doubling gents).
Firstly, even when limited to plants, each species of plant has multiple cyclin genes that could be characterized as cyclin D (CYCD) family genes. For example, Arabidopsis has 10 CYCD genes in seven subgroups (page 1558). Menges also identifies 22 CYCD genes in poplar (Populus trichocarpa) genome (page 1558) and 14 CYCD genes in rice genome which fall into six or seven subgroups (page 1559). Godinez-Palma reports “maize cells contain 17 different genes coding for D-type cyclins” (page 5562).
Secondly, the claimed genus defined by “at least 95% identity to SEQ ID NO:23” encompass an enormous number of structurally distinct polypeptides. SEQ ID NO:23 is 355 amino acids in length. A 95% identity threshold permits up to approximately 17 amino acid differences relative to SEQ ID NO:23. Even limiting the analysis to substitutions (and not insertions/deletions). The number of possible sequence variants within that permitted sequence space is extremely large (i. e., substitutions at many combinations of positions, each with multiple alternative residues). Accordingly, the claimed genus encompasses a large number of structurally distinct polypeptides, each required by the claim to satisfy the same highly specific biological function in the context of the in vivo egg-cell chromosome doubling. For example, a mutation could also change the function of a gene. A study analyzing leaf-petal allometry in Arabidopsis identified natural variations in the cell division regulator CYCD2;1 as potentially responsible for distinct growth traits, including leaf and petal characteristics. A unique variant of this gene was found exclusively in the Hi-0 strain (Li, page 6).
In contrast to the broad scope, the Specification has provided enabling guidance for ZM-CYCD2 (DNA SEQID NO:17) encoding SEQ ID NO:23, wherein activity during female gametogenesis provided chromosome doubling activity in vivo to create a diploidized embryo having only maternal chromosomes (paragraph 0172-0192). The specification further provides illustrative plasmid/cassette contexts in which ZM-CYCD2 is placed under particular promoters/regulatory elements for delivery via pollen or early zygotic expression (e. g., plasmids listing ZM-CYCD2 as the doubling factor in tables describing transformation constructs and methods for generating transformed haploid inducer lines and performing haploid induction crosses) (example 1- 4).
However, the Specification has not provided enabling guidance for the full scope of the claimed genus of polypeptides having at least 95% identity to SEQ ID NO:23 to have the required function of inducing chromosome doubling of an egg cell in vivo, in the claimed crossing context, and yielding a diploidized embryo that lacks the introduced polypeptide. In particular, the specification does not teach which of the many permitted SEQ ID NO:23-like variants (including those with up to ~17 amino acid difference) will retain the required chromosome-doubling activity, under what expression timing/location, and in what plant genetic backgrounds, such that the claimed results is achieved without chemical doubling.
It is unpredictable how the broadly claimed sequence variants within the ≥95% identity genus would affect the required chromosome-doubling function. Cyclin proteins are cell-cycle regulators whose activity depends on precise structural determinants and interaction capabilities (Godinez-Palma, page 5661) (e. g., interaction with partner proteins and pathway components, appropriate expression timing, and effective activity in the relevant cell type). Thus, sequence variation permitted by the claims can alter the functional properties relevant to the claimed outcome, including whether the protein will produce the specific biological effect of egg-cell chromosome doubling in vivo, rather than other cell-cycle perturbations (e.g., altered division arrest, abnormal development, infertility, or lethality). In this case, the claims impose a highly specific functional requirement (egg-cell chromosome doubling producing a diploidized embryo with only maternal chromosomes, without chemical doubling agents), yet the specification does not provide guidance that correlates the broad identity-based sequence space to that specific function.
With regard to the above discussed unpredictability, neither the instant application nor the prior art cited in the specification provides sufficient teachings to overcome the deficiency for the entire claimed genus. Applicant has provided working guidance for the specific ZM-CYCD2 embodiment (SEQ ID NO:23 as encoded by SEQ ID NO:17) in particular construct/promoter contexts and within the described haploid induction framework. But the specification does not provide commensurate enabling guidance for the full breadth of SEQ ID NO:23-like variants permitted by the ≥95% identity definition.
Thus, in view of the unpredictability associated with cyclin-mediated cell-cycle perturbation in vivo, the unpredictability of how sequence variation with the ≥95% identity genus impacts the required egg-cell chromosome-doubling function, the lack of enabling guidance from either the instant disclosure or the art, and breath and diversity of the embodiments encompassed by the claimed genus, the lack of sufficient working examples, and the level of the art at the time of the invention, one of ordinary skill in the art must rely on undue trial and error experimentation to make and test the numerous genes having unspecified mutations, in order to make and/or use the invention commensurate to the full scope of these Claims.
For at least this reason, the Specification does not teach a person with skill in the art how to make and/or use the subject matter within the full scope of these Claims without undue experimentation.
Response to Applicant’s Remarks:
Applicant’s arguments filed in response to the previous Office action filed on 7/9/2026 have been fully considered but are not persuasive for the reasons set forth below.
Argument: the amendment to at least 95% identity overcomes the 112a rejections.
Applicant argues that the amendment narrowing the claimed polypeptide form at least 90% identity to at least 95% identity to SEQ ID NO: 23 overcomes the written-description and enablement rejections.
The argument is not persuasive. Narrowing the identity threshold reduces the breadth of the claimed sequence genus, but it does not resolve the absence of representative functional variants or structure-function guidance. SEQ ID NO: 23 contains 355 amino acids, and 95% identity threshold permits approximately 17 amino-acid difference, depending upon the alignment methodology and treatment of gaps.
The specification does not disclose which of the permitted amino-acid changes retain the claimed egg-cell chromosome-doubling function, which positions must remain unchanged, or which combinations of changes are tolerate. The amendment therefore narrows, but doe not eliminate, the original written-description and enablement deficiencies.
Argument: D-type cyclins are a recognized and evolutionarily conserved family.
Applicant’s argument that D-type cyclins are a recognized and evolutionarily conserved protein family and that variants having 95% identity would retain CYCD2 structural hallmarks, the Office agree that D-type cyclins share conserved structural features. However, the claims require more than general D-type cyclin activity. The claimed polypeptides must induce chromosome doubling of an egg cell in the claimed crossing method. The specification does not establish that conservation of general cyclin structure is sufficient to retain this specific biological function, nor does it disclose a structure-function relationship or representative functional variants demonstrating that the claimed activity is maintained across the full scope of the ≥95% identity genus.
Conclusion
No claims are allowed.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to YANXIN SHEN whose telephone number is (571)272-7538. The examiner can normally be reached Monday-Friday.
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/YANXIN SHEN/Examiner, Art Unit 1663
/WEIHUA FAN/Primary Examiner, Art Unit 1663
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