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 .
Claims 25-44 are pending and examined on their merit herein.
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 25-44 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a modified tobacco plant with a recombinant DNA construct comprising a heterologous axillary meristem-specific promoter set forth in SEQ ID NO: 117 (promoter P15) operably linked to polynucleotide encoding a polypeptide set forth in SEQ ID NO: 233, does not reasonably provide enablement for a tobacco plant with a recombinant DNA construct comprising a heterologous promoter other than that set forth in SEQ ID NO: 117 (promoter P15) operably linked to polynucleotide encoding a polypeptide having an amino acid sequence 95% identical to SEQ ID NO: 233; especially with SEQ ID NO: 148. 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.
Here, the claims are broad in scope in the following manner:
a polynucleotide encoding a polypeptide having an amino acid sequence at least 90% identical or similar to SEQ ID NO: 233, or a polynucleotide having nucleic acid sequence at least 95% identical to SEQ ID NO: 232;
any “axillary meristem-specific promoter”, including a nucleic acid sequence at least 95% identical to SEQ ID NOs: 113, 115, 116, 118, 148, 149, 151, 153, 155, 157, 159, or 204;
It should be noted that a nucleic acid sequences having 95% identity could encode a protein having 85% amino acid sequence identity with the protein encoded by SEQ ID NO: 232 (i.e., SEQ ID NO: 233), due to the nature of the genetic codons (considering for example a DNA sequence encoding 100 codons—300 nucleotide in length; 5% sequence variation –15 nucleotides-- could potentially result in 15 codons being altered, therefore resulting in 15% amino acid sequence difference, i.e. 85% identity).
In contrast to the broad scopes claimed, Applicant taught modified tobacco plants having the polynucleotide set forth in SEQ ID NO: 232 driven by Promoter P15 (SEQ ID NO: 117), that exhibit reduced sucker growth compared to control tobacco plants. (Example 15, [0281]).
Applicant has not provided teachings of any variants—of any sequence identity-- of SEQ ID NO: 233 or 232; or that under the expression control of any other promoter than Promoter P15 (SEQ ID NO: 117). Applicant has not provided any teachings of any variants—of any sequence identity—of the promoter sequences.
Applicant has not provided any enabling teachings regarding the structural determinant of axillary bid specific expression in a promoter sequence. Applicant has not provided enabling teachings regarding the axillary bud specific expression by the promoters defined in SEQ ID NOs: 113, 115, 116, 118, 148, 149, 151, 153, 155, 157, 159, or 204, or nucleic acid sequence at least 95% identical to any of them.
The ordinary skills in the art cannot reasonably predict the functions of the broadly claimed protein variants, in conjunction with broad range of promoters and promoter variants, in term of modifying tobacco plant traits.
The prior art teaches that the protein set forth in SEQ ID NO: 233 is a constitutively active form of mitogen-activated protein kinase kinase of Nicotiana, with two amino acid substitutions compared with the wild type protein (NtMEK2DD). NtMEK2 is involved in programmed cell death and is activated by pathogen in fection. Expressing mitogen-activated protein kinase kinase is in Nicotiana produces unexpected results. Takabatake et al (2007, Plant Cell Physiol. 48(3): 498–510) teaches that transient expression of NtMEK2DD, a constitutively active form of a tobacco MAPK kinase upstream of WIPK and SIPK, induces HR-like cell death in tobacco; programmed cell death has physiological roles in elimination of diseased cells and of unwanted cells during development. (p. 499). Lu et al (2013, "Cotton GhMKKl Induces the Tolerance of Salt and Drought Stress, and Mediates Defense Responses to Pathogen Infection in Transgenic Nicotiana benthamiana", PLOS ONE 8(7): e68503, (pages 1-14 )) disclose overexpressing GhMKKl, a mitogen-activated protein kinase kinase polypeptide, in tobacco enhanced the plant's tolerance to salt and drought stresses as well as up-regulate pathogen-associated biotic stress (abstract). Lu et al also report overexpression of GhMKKl also increased the plants susceptibility to the pathogen Ralstonia solanocearum by reducing the expression of PR genes.
Jeong et al (2008, Plant Pathol. J. 24(4): 375-383) teaches that transgenic rice plants expressing an active tobacco mitogen-activated protein kinase kinase NtMEK2DD induce multiple defense responses. It is noted that Jeong uses an inducible promoter to drive the expression of this constitutively active protein which triggers cell death.
These results demonstrate that overexpressing a mitogen-activated protein kinase kinase in plants does not always produce a desired result, and the overexpression has to be carefully controlled.
The Applicants do not identify essential regions of the protein of SEQ ID NO: 233 nor do Applicants describe any polynucleotide sequences that encode a polypeptide having at least 90% identity to SEQ ID NO: 233, wherein a tobacco plant comprising said polypeptide exhibits no or reduced suckers compared to a control tobacco plant. The state-of-the-art is such that one of skill in the art cannot predict which nucleic acids that encode a polypeptide having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 233 will encode a protein with the same activity as the protein encoded by SEQ ID NO: 232. The prediction of protein structure from sequence data and, in tum, utilizing predicted structural determinations to ascertain functional aspects of the protein, is extremely complex, and the positions within the protein's sequence where amino acid substitutions can be made with a reasonable expectation of aintaining function are limited (Bowie et al, (1990, "Deciphering the Message in Protein Sequences: Tolerance to Amino Acid Substitutions", Science 247: 1306-1310), see especially page 1306). Proteins may be sensitive to alterations in even a single amino acid in a sequence. For example, the replacement of a glycine residue located within the START domain of either the PHABULOSA or PHAVOLUT A protein receptor with either an alanine or aspartic acid residue, alters the sterol/lipid binding domain (Emery, John F., et al. "Radial patterning of Arabidopsis shoots by class III HD-ZIP and KANADI genes." Current Biology 13.20 (2003): 1768-1774). Benfey et al (1990, "The Cauliflower Mosaic Virus 35S Promoter: Combinatorial Regulation of Transcription In Plants", Science 250:959-966) teach that the 35S CaMV promoter consists of domains that individually regulate spatial expression within plants. "The combination of each of the five B subdomains with domain A results in an expression pattern that differs from that of the individual subdomains or domain A" (page 961, left column, 2nd paragraph). In other words, deleting a required domain will jeopardize the proper spatial and temporal expression pattern. In addition, Benfey et al (1989, "The CaMV 35S Enhancer Contains At Least Two Domains Which Can Confer Different Developmental and Tissue Specific Patterns", EMBO J, 8(8):2195-2202; page 2200, left column 2nd paragraph) teach that not only are the promoter domains important for specifying proper spatial and temporal expression but that when all domains were present, the quantity of expression increased.
Therefore, one of skill in the art would not expect a promoter sequence exhibiting at least 90% sequence identity to SEQ ID NO: 117 to have the same spatial and temporal expression pattern as the promoter sequence of SEQ ID NO: 117. Since promoter SEQ ID NO: 148 has no resemblance of Promoter P15, there is no reasonable expectation that SEQ ID NO: 148 would drive NtMEK2DD to produce reduced numbers of suckers.
Applicants have not demonstrated that any axillary meristem-specific promoter—or any variants thereof-- will produce the desired result when operably linked to a nucleic acid encoding a mitogen-activated protein kinase kinase polypeptide. As defined above, an axillary meristem-specific promoter may only express in any one of the layers or only one of the zones of a meristem which is different than the expression of the promoter P15. It is therefore unclear if expressing a transgene encoding a mitogen-activated protein kinase kinase polypeptide with any axillary meristem-specific promoter as defined by applicants will produce the expected result.
In the absence of guidance, undue trial and error experimentation would be required for one of ordinary skill in the art to screen through the multitude of non-exemplified sequences, either by using non-disclosed fragments of any nucleic acid encoding any mitogen-activated protein kinase kinase polypeptide as probes or by designing primers to undisclosed regions of any mitogen-activated protein kinase kinase polypeptide and isolating or amplifying fragments, subcloning the fragments, producing expression vectors and transforming tobacco plants therewith, in order to identify those, if any, that when over-expressed have no or reduced suckers as compared to a control tobacco plant.
Therefore, given the breadth of the claims; the lack of guidance and examples; the unpredictability in the art; and the state-of-the-art as discussed above, undue experimentation would be required to practice the claimed invention, and therefore the invention is not enabled.
Conclusion
No claims are allowed.
Claims 25-44 are free of the prior art because there is no prior art teaching or suggesting the claimed cured tobacco material from a modified tobacco plant comprising no or reduced suckers compared to a control tobacco plant of the same variety when grown under comparable conditions, wherein the modified tobacco plant comprises a heterologous axillary meristem-specific promoter functional in a central zone, a peripheral zone, a rib zone, or any combination thereof operably linked to a nucleotide sequence encoding a mitogen-activated protein kinase kinase polypeptide having an amino acid sequence at least 95% identical or similar to SEQ ID NO: 233.
The closest prior art is Jin (The Plant Journal (2003) 33, 719–731) which teaches modified tobacco plant expressing a modified mitogen-activated protein kinase kinase polypeptide NtMEK2, the wild type of which is encoded by the instant SEQ ID NO: 233. However, Jin does not teach or suggest the NtMEK2 under a heterologous axillary meristem-specific promoter functional in a central zone, a peripheral zone, a rib zone, or any combination thereof, or the reduction in suckers in the modified tobacco plant.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to WEIHUA FAN whose telephone number is (571)270-0398. The examiner can normally be reached Monday-Friday, 9-5.
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WEIHUA . FAN
Primary Examiner
Art Unit 1663
/WEIHUA FAN/Primary Examiner, Art Unit 1663
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