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 .
Claim Status
Claims 1-3, 7, 9-13, 15, 18-22, 26-33, 35-37 & 39 are examined on the merits.
Claims 4-6, 8, 14, 16-17, 23-25, 34 & 38 are canceled.
Priority
Claims 1-3, 7, 9-13, 15, 18-22, 26-33, 35-37 & 39 receive the U.S. effective filing date of 25 March 2022.
Previous objection to the specification is withdrawn in light of Applicant’s amendment to the specification.
Previous rejection of claim 16 under 35 U.S.C. 112(d) is withdrawn in light of Applicant’s amendment to the claims.
Previous rejection of Claim 7 under 35 U.S.C. 112(b) is withdrawn in light of Applicant’s amendment to the claims.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-3, 7, 9-13, 15, 18-22, 26-33, 35-37 & 39 are rejected under 35 U.S.C. 103 as being unpatentable over U.S. Patent Application Publication US 2005/0257289A1 [Published 17 Nov 2005], hereafter referred to as Gordon-Kamm et al., in view of Akhtar [Journal of Genetics, Volume 91, pages 385–395, (2012); Published 19 Dec 2012].
The claims are drawn to production of doubled haploid (DH) plants using a fusion protein comprising ODP2, WUS2, and CBF1a.
Gordon-Kamm et al. teaches production of DHs using a fusion protein of ODP2 and WUS2 [p.29, Example 16, Expression of ODP2 in Double-Haploid Production]. They teach transformation of plants with ODP2 fusion protein constructs and regeneration of transgenic plants (i.e. ‘T0 plants’) via pollination with donor pollen [par.210-211]. They describe the use of marker genes or other genes ‘conferring a desirable trait’ in heterologous vector constructs with ODP2 or fusions thereof [par.215].
They do not teach the CBF1a component of the fusion protein.
Akhtar teaches the use of CBF1 transcription factors in plants, specifically their use in stress response [p.385, Abstract]. Such CBF1 factors are important in stress-responsive gene expression [p.386, col.2, par.1 – p.387, col.2, par.1]. It is known that the process of abnormal chromosome reduction and doubling (i.e. DH production) is a stressful event for plants, often with low survival/recovery rates. They teach that genetic modification of plants using CBF genes as part of multi-component gene constructs (i.e. fusions) can benefit plants experience such stresses [p.393, col.1, par.1].
Before the effective filing date of the claimed invention, it would have been obvious to one of ordinary skill in the art to modify transgenic methods of using ODP2 fusion constructs to generate DH plants as taught by Gordon-Kamm et al. from 2005 to methods using newly described transcription factor components in heterologous constructs including CBF1 as described in Akhtar. It would be obvious to utilize the method of Gordon-Kamm et al., directed to DH production, with newly described tools of molecular biology as they become available. One would apply the known technique (the improved CBF1 component) to a known method (the use of ODP2 fusion constructs) for improved results in stress response / DH production.
One of ordinary skill in the art would be motivated to do so because Gordon-Kamm’s method has clear value in the production of DHs but can be improved based on newly relevant transcription factors, or other relevant genes, which can help mitigate stress and survival of embryos undergoing double-haploidization. The use of the CBF1 factor is such a molecular ‘tool’ which was developed subsequent to the initial publication of Gordon-Kamm et al. in 2005, and had been specifically shown to increase stress resistance.
One would be motivated to integrate more recent techniques into this known DH production method to increase survival rate, and thus maximize the number of DH lines returned per breeding cycle. Akhtar clearly indicates that use of CBF genes as part of multi-component gene constructs (i.e. fusions) can benefit plants under stress [p.393, col.1, par.1]. There would be strong motivation to ‘plug in’ a newly described genetic element associated with stress tolerance in plants to aid in the recovery (i.e. survival) of new DH lines. The improved construct would represent savings in both time and money to a plant breeder.
Regarding claims 1-3, 7, 11-13, 15-16 & 31-33; one of ordinary skill in the art would have been motivated to use an ODP2 as a fusion construct to generate DH plants because it would improve efficiency of their DH process and thus improve the cost efficiency of their plant breeding efforts. Gordon-Kamm et al. teaches transformation of plants with ODP2 fusion protein constructs and regeneration of transgenic plants (i.e. ‘T0 plants’) via pollination with donor pollen [par.210-211]. They describe the use of marker genes or other genes ‘conferring a desirable trait’ in heterologous vector constructs with ODP2 or fusions thereof [par.215]. Such a molecular tool that accelerates the development of DH plants, and thus inbred lines, would be highly useful and valuable to a plant breeder as a way to reduce the number of years required to develop new breeding material.
Regarding claims 9-10, 18-19; one of ordinary skill in the art would have been motivated to combine the teachings of Gordon-Kamm with those of Akhtar because the invention described by Gordon-Kamm et al. is clearly valuable in accelerating the plant breeding process through DHs, and Akhtar presents the CBF1 transcription factor as a genetic component that can increase plant stress resistance, and thus survival. The DH process is incredibly stressful on plant embryos which often have a low survival (i.e. return) rate.
The use of CBF1 factors is such a molecular ‘tool’ which developed after the initial publication of Gordon-Kamm et al. in 2005. The more recently described CBF1 is directed to improved stress response/survival in plants, and one would be highly motivated to integrate such improved molecular tools into known methodology to increase efficiency, as is routine in plant breeding.
Claims 20-22, 26-30, 35-37 & 39 are rejected under 35 U.S.C. 103 as being unpatentable over Gordon-Kamm et al. and Akhtar as applied to claims 1-3, 7, 9-13, 15-16, 18-19 & 31-33 above, and in further view of Wada [BMC plant biology, 2020-05, Vol.20 (1), p.234-234, Article 234; Published 25 May 2020].
The claims are drawn to production of DH plants using a fusion protein comprising ODP2, WUS2, CBF1a and the use of Cas polypeptides for genome-editing.
Gordon-Kamm et al. and Akhtar teach production of DHs using a fusion protein of ODP2 and WUS2 in conjunction with CBF1 transcription factors, as discussed previously [see above, p.5-7].
They do not describe gene editing or use of Cas polypeptides.
Wada teaches the use of gene editing, specifically use of Cas polypeptides and guide nucleotides [p.1, Abstract; p.1, col.2, par.2—p.2, col.2, par.2]. They teach the relevant Cas9 polynucleotides capable of being deployed in gene editing approaches [p.8, Table 2]. They describe the potential benefits of using gene editing to genetically modify plants [p.9-10, Conclusions].
Before the effective filing date of the claimed invention, it would have been obvious to one of ordinary skill in the art to combine the teachings of Gordon-Kamm et al. and Akhtar with use of gene editing and CRISPR/Cas9 systems as taught by Wada in order to apply the known technique of gene editing to the established ODP2-fusion method in order to improve the method and predictably improve the precision of targeted genetic modifications.
One of ordinary skill in the art would be motivated to do this because they could more quickly or efficiently produce ODP2-fusion DHs because gene editing enables the making of more precise modifications to any of the genes or sequences critical to the ODP2-fusion DH system. This would allow one to more precisely modify the genes involved in the system, including potential transfer of the ODP-2 gene to a target plant, into a precise location in the target plant’s genome.
Wada clearly describes the potential benefits of using gene editing to genetically modify plants and why the technique would be helpful [p.9-10, Conclusions]. The benefits of utilizing the more recent gene-editing approaches which they lay out, including accelerating research projects via precise and easy genome modifications, would be apparent to a plant breeder seeking improved molecular breeding techniques to apply to established methods such as that of Gordon-Kamm et al. which rely on the generation of fusion constructs, and transformation of plants, having very specific genetic elements and sequences involved.
One of ordinary skill in the art would have been motivated to combine these teachings because the invention described by Gordon-Kamm et al. is clearly valuable in accelerating plant breeding via DHs. One would want to utilize that method with useful, newly described tools of molecular biology, as they become available in order to improve results of the known ODP2 method. Gene editing is one such tool which has developed since the initial publication of Gordon-Kamm et al. in 2005, that allows targeted transfer of ODP2 into a plant’s genome. Integrating this more recent molecular breeding approach into known methodology would improve DH production efficiency because of its specificity and ability to reduce the amount of post-transformation screening of lines to ascertain the random insertion site(s) obtained via older genetic modification techniques. Improving established systems through use of widely known, new genomic advances that predictably increase the precision or efficiency of genetic modification is routine in plant breeding.
Regarding claims 20-22 & 26-29; prior art details the production of DH plants having the ODP2 polypeptide (SEQ ID NO:2) and WUS fusion construct produced from transgenic cells, regenerated from haploid embryos via use of marker gene [see Gordon-Kamm; p.29, Example 16, Expression of ODP2 in Double-Haploid Production; par.210-211; par.215]. Prior art provides embodiments wherein this is achieved without the use of a chromosome doubling agent (i.e. spontaneous doubling) [Gordon-Kamm, par.156], and describes inclusion beneficial cyclins such as the Baby Boom protein [Gordon-Kamm, par.6-7]. Fusion proteins using CBF1a are described [see Akhtar; p.393, col.1, par.1].
Regarding claims 30, 35-37 & 39, which are significant restatements of prior claims with the added limitation of using gene editing; genome editing is taught by Wada, which employs use of Cas polypeptide(s) and guide polynucleotides [see Wada p.1, col.2, par.2—p.2, col.2, par.2, p.9-10].
For these reasons, claims 20-22, 26-30, 35-37 & 39 are rejected because the claimed invention would have been obvious in view of prior art at the time of filing.
Response to Arguments
Applicant urges previous rejection of claims 1-3, 7, 9-13, 15-16, 18-19 & 31-33 as obvious under 35 U.S.C. 103 is improper because the Office has not adequately addressed the specific sequence-defined ODP2 limitation or identify where cited references teach chromosome-doubling functionality attributed to the claimed ODP2 polypeptide [Remarks, p.11, ¶.1-3]. Applicant argues that the claimed ODP2 polypeptide is a truncated form of ODP2 [p.10, ¶.8].
This is not persuasive because Applicant’s amended claims require an ODP2 polypeptide which merely comprises the recited sequence of 90% identity to SEQ ID NO.2. Applicant admits this sequence is a truncated form (i.e. a fragment) of ODP2, which is the polypeptide taught by the prior art, and cited in the previous rejection [Gordon-Kamm et al. p.29, Example 16, Expression of ODP2 in Double-Haploid Production]. The instant Application therefore claims a sub-fragment or sequence of the previously described ODP2 molecule. One would reasonably consider that a sub-fragment, or part of, a previously described sequence would match the larger sequence of which it simply a smaller truncated fragment. The complete ODP2 protein would thus comprise this fragment (i.e. the current claims read on the complete ODP2 protein).
Comparison of sequences from the prior art of Gordon-Kamm et al. supports this rejection. The ODP2 polypeptide claimed in Gordon-Kamm et al. is described as SEQ ID NO.2. Protein comparison between SEQ ID NO.2 of Gordon-Kamm et al. and SEQ ID NO.2 of the instant application shows the ODP2 sequence of the prior art to have 99.75% sequence identity to SEQ ID NO.2 of the instant application:
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627
1162
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868
1288
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871
852
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Applicant’s arguments are directed solely to a lack of sequence identity between the currently claimed SEQ ID NO.2 and the ODP2 protein of Gordon-Kamm et al. which was previously cited by the Office. Applicant is silent as to any other reasons for refuting obviousness rejections of their claims provided in the previous non-final rejection, and contends that the Office has failed to make a case of prima facie obviousness due to lack of meeting the recited sequence similarity requirement to ODP2.
However, review of sequence information provided in the prior art clearly demonstrates the previously described ODP2 protein sequence both meets and exceeds the limitation of 90% identity to the truncated sequence as currently claimed in the instant application and argued by Applicant.
For this reason, all claims are obvious in view of prior art and rejected.
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 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.
Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KEITH R WILLIAMS whose telephone number is (571)272-3911. The examiner can normally be reached Mon - Fri, 9:30 - 5:30 EST.
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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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/KEITH R. WILLIAMS/Examiner, Art Unit 1663
/Amjad Abraham/SPE, Art Unit 1663
