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 92-94 are pending.
Claims 92-94 are examined on the merits.
Claim Objections
Claim 92 is objected to because the phrase “cleaves SEQ ID NO: 68 of SEQ ID NO:71” is inconsistent and unclear. Applicant is required to amend claim 92 to “SEQ ID NO: 68 or SEQ ID NO:71” or otherwise provide appropriate corrective language.
Claim Rejections - 35 USC § 112
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 93-94 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.
Claim 93 is rejected as being indefinite for dependency on canceled claim.
Claim 94 is rejected as being indefinite for dependency on canceled claim.
Claim 93 is interpreted as depends on claim 92. Claim 94 is interpreted as depends on claim 92. It should be noted that such treatment does not relieve Applicants of the responsibility of responding to this rejection. Moreover, if the intended meaning of the claim is different than that posited by the Examiner, additional 35 U.S.C. § 112 and prior art rejections may be readily applied in a subsequent office action.
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 92-94 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.
The claims are rejected for lacking adequate written description support regarding the broad scope of the following.
Claim 92 recites a maize plant comprising a complex transgenic trait locus comprising at least first and second altered endogenous targe sequences, wherein each alteration comprises a heterologous polynucleotide, and wherein at least one double-strand-break-inducing agent cleaves SEQ ID NO: 68 or SEQ ID NO: 71.
The specification identifies SEQ ID NO: 68 and SEQ ID NO: 71 as MHP target sites within a maize genomic region (pa0397 and fig 8). The specification further discloses engineered meganucleases and associated activity data for selected target sites including MHP14, MHP55, and MHP77 (pa0399-0411, Table 2 and 3). However, the specification does not disclose the nucleotide sequence, amino acid sequence, structural characteristics, engineering modifications, or other identifying features of a double-strand-break-inducing agent that cleaves SEQ ID NO: 68 (MHP1) or SEQ ID NO:71(MHP42). Although the specification generally lists multiple classes of double-strand-break-inducing agents, including endonuclease, TAL effector nuclease, zinc finger nuclease, recombinases, transposases, and topoisomerase (pa0236-0267), the specification does not disclose any specific agent form any of these classes that is structurally identified or experimentally demonstrated to recognize and cleave MHP1/SEQ ID NO: 68 or MHP42/SEQ ID NO: 71.
Further, the specification discloses heterologous polynucleotide insertion at MHP14 through homologous recombination (pa0401-0410). However, the specification does not disclose insertion of a heterologous polynucleotide at MHP1 (SEQ ID NO: 68), insertion of a heterologous polynucleotide at MHP42 (SEQ ID NO: 71), or a maize plant comprising first and second altered endogenous target sequences at those sites wherein each alteration comprises a heterologous polynucleotide.
Accordingly, although the specification identities SEQ ID NO:68 and SEQ ID NO: 71 as candidate target sites, the specification does not reasonably convey possession of the claimed maize plant comprising first and second altered endogenous target sequences, wherein each alteration comprises a heterologous polynucleotide, and a double-strand-break-inducing agent that cleaves SEQ ID NO: 68 or SEQ ID NO:71. Therefore, the specification fails to provide adequate written description support for the full scope of claim 92. Claim 93 and 94 are rejected for at least the same reasons.
Scope of Enablement
Claims 92-94 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 certain disclosed embodiments; does not reasonably provide enablement for the full scope of the claimed invention, including a maize plant comprising first and second altered endogenous target sequences wherein each alteration comprises a heterologous polynucleotide and wherein at least one double-strand-break-inducing agent cleaves MHP1/SEQ ID NO: 68 or MHP42/SEQ ID NO:71. as of the filing date. 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 92 requires a maize plant comprising first and second altered endogenous target sequences, each alteration comprising a heterologous polynucleotide, wherein at least one double-strand-break-inducing agent cleaves SEQ ID NO: 68 or SEQ ID NO: 71.
The specification generally describes the use of engineered meganuclease and other double-strand-break-inducing agents (pa0236-0278). The specification also describes engineering meganucleases for selected MHP target sites and provides experimental data for MHP14, MHP55, and MHP77 (pa0399-0411, Table 2 and 3). However, the specification does not provide a double-strand-break-inducing agent that cleaves SQ ID NO: 68 or SEQ ID NO: 71, nor does it disclose the engineering modifications, amino acid substitutions, nucleotide sequences, screening methodology, activity validation data, or cleavage data necessary to generate such agents.
The specification further lacks working examples demonstrating insertion of heterologous polynucleotide at SEQ ID NO: 68 (MHP1) or SEQ ID NO: 71 (MHP42), despite claim 92 requiring a maize plant comprising altered endogenous target sequences and a double-strand-break-inducing agent directed to those target sites.
The specification does not disclose the structure, amino acid sequence, engineering modification, or method of obtaining a meganuclease capable of specifically recognizing and cleaving the MHP1 target site (SEQ ID NO: 68) or the MHP42 target site (SEQ ID NO:71). Because the development of meganucleases with new target specificities was recognized in the art as difficult and unpredictable. Quinlan (Anna Quinlan, Bio-Rad (2016)) discloses, engineering meganucleases to recognize and cleave new target sequences is highly challenging and unpredictable at the time of filing. Meganucleases typically require substantial protein reengineering to achieve new target specificities, and their design has been characterized as “extremely difficult”, with reengineering for new specificities identified as a significant targeting constraint (Table 1), a person of ordinary skill in the art would have been required to undertake extensive protein engineering, screening, and functional validation to identify suitable nuclease for these target sequence.
Accordingly, the specification does not enable the full scope of claimed invention without undue experimentation. Dependent claims 93 and 94 are rejected for at least the same reasons.
Conclusion
No claims are allowed.
The closest prior art of record, Shukla (Vipula K. Shukla et. al., Nature (2009) Vol 459: 21, pp437-443), is directed to targeted genome modification in maize using designed zinc finger nucleases. Shukla teaches inducing a double-strand break at an endogenous maize target locus and introducing a heterologous donor molecule to obtain targeted addition of herbicide-tolerance gene at the intended locus. However, Shukla does not teach or suggest a maize plant comprising a complex transgenic trait locus having first and second altered endogenous target sequences located on the same arm of the same chromosome, wherein each alteration comprises a heterologous polynucleotide, and wherein at least one double-strand-break-inducing agent cleaves the specific maize MHP target site of SEQ ID NO: 68 or SEQ ID NO:71. Shukla is directed to targeted modification of a single endogenous maize locus, not the claimed complex transgenic trait locus comprising multiple altered endogenous target sequences in physical linkage. Accordingly, Shukla does not anticipate or render obvious the claimed invention.
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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