Inari Ex. 1010
`Inari Agric. v. Corteva Agriscience
`PGR2023-00022
`Page 00001
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`I received two Bachelor of Science degrees (B.5.} in
`science, and plant bioiechnelogy.
`Crop and Soil Science and Agricultural Biochemistry from Michigan State University, a
`Master of Science (MLS.) degree in Crop Science/Weed Science from Washington State
`University, and a Doctorate of Philosophy (Ph.D.} from Michigan State University in
`Herbicide Physiology and Plant Biotechnology. [am a co-inventor on over SO granted US.
`patents, and an author of 20 peer-reviewed scientific journal articles, My research has been
`in the areas of crop protection and trait discovery and developrnent. Lam an expert in the
`Held of herbicide physiology and herbicide resistance, weed control, andtrait discovery
`and development.
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`ho
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`lam an inventor and am very familiar with the contents of the subject application, US.
`Patent Application No. 15/468,494 (“the ‘494 Application”). Lam informed and believe
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`that the claims currently pending in the ‘494 Apnlication reflect those attached hereto as
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`Appendix L Ihave reviewed and understand those claims.
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`lundersiand that this Declaration will be filed in support of the patentability of the claims
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`pending in the “404 annlication.
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`i understand that inthe final Office Action of May 3, 2021 in the ‘494 Application, the
`U.S. Patent and Trademark Office has rejected claims 27-29, 41-54, and 37-59 ofthe ‘494
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`Application as being uapatentable over Kaphammer (U.S. Patent 5,608,147) in view of
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`Schieinitz et al (September 2004, Applied and Environmental Microbiology 749): $357~
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`3363) and Pallett et al CLS. Patent 7,205,561 BL, § 371 (c)(1) date of 15 June 1998),
`{Office Action at point 6).
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`[have been asked fo comment on whether a person of ordinary skill in the art at the time of
`the invention in 2005 would have thought the transgenic plant cell, encompassed by the
`claims, or the use of a plant comprising such cells in a method to control weeds, was
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`obvious in light of the prior art teachings.
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`Prior to 2005, the scientific community had recognized that the TWA gene conld be
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`expressed in transgenic plants io impart 2,4-D resistance in dicot plants (¢.g., catton and
`tobacco) normally sensitive to 2,4-D (Sueber ef af, 1984; Lyon eral, 1989; Lyon ef all,
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`2
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`1993). Furthermore, a large number of fdA-type genes that encode proteins capable of
`degrading 2,4-D had been identified fromthe environment and deposited into the Genbank
`database. However, although many o-ketoglutarate-dependent dioxygenases were known,
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`no gene except dA had exhibited the ability to degrade phenoxyauxin herbicides when
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`inserted into plant cells.
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`. Af the tome of the invention, the standard practice usedfor identifying proteins exhibiting a
`similar functionality to a known protein was to screen for proteins having a high level of
`amino acul sequence identity with the known protein, and then test those selected proteins
`for activily, Accordingly, to hlentify ofd4-type genes that encode proteins capable of
`degrading 2,4-D when expressed in plants (similar to the activity of the 4A gene), one
`would traditionally select a protein having high sequence identity with TEA.
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`. The sdpA gene from Delfita acidivarans (as disclosed in Westendorfet al., 2002, 2603 and
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`ochisinitz et al} encodes an enzyme (SdpA} that is distantly related to TfdA. SdpA had
`previously been shown lo degrade S-dichloroprop (Westendorf et al., 2002 and 2003) but
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`also 2,4-D (albeit, relatively poorly) based on in vitro assays. More particularly, the
`Westendort 2003 article (Acta Biotechnol 23:3 shows preference of S-dichlorprop over
`2.4-D by »3-fold (see Table 3). Furthermore, Schieitniz et al (cited by the Examiner) states
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`on page 3363 (first column,first full paragraph) that “SdpA shows greatest activity with the
`= enantiomers of mecoprop and dichlorprep but has some activity toward 2,4-D".
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`However, the recited enzymatic activity of SdpA was limited to in vitro assays and SdpA
`was known to have low homology to ThA 1% amino acid identity). At the time of the
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`invention, SdpA had never been expressed in plants, sor was there any motivation to do so.
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`. Those skilled in the art appreciate that there is a high level of unpredictability associated
`with expressing bacterial genes in plant systems. This fact is highlighted by comparing the
`activity of lwo UGA homologs expressed m plants. Appendix If provides dataoriginally
`presented in Example (7.1-17.5 of US Patent no 7,838,743 comparing the activity of two
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`@-KG dioxygenase enzymes referred to as AAD-1 and AADB-2.
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`i0. AAD-2 is more closely related (about 44%) at the sequence level io tidA than is AAD-1
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`{about 27%). Furthermore, AAD-2 was determined to have Vmax almost 8-fold higher than
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`AAD-1 for 2,4-D, based on a standard in vitre assay. However, while, AAD-2 has a higher
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`percentage sequence identity with thiA relative to AAD-1, and in spite of AAD-2 having
`significantly higher in vitro activity for degrading 2,4-D, AAD-2 was surprisingly inactive
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`when expressed in plants, while AAD-1 was very active.
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`PE. in my opinion, one of ordinary skill in the art, being cognizant of the unpredictability
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`associated with expressing bacterial genes in plant systems, would not have been motivated
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`to specifically select a bacierial gene having low sequence identity to ifdA when attempting
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`io express another gone that would provide tolerance to a phenoxy auxin herbicide. Ai the
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`time of the invention there were over 100 other known tfdA homologs that share higher
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`sequence identity with the dA gene than sdpA. Each of these homologs represent a gene
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`thal one could consider as a possible candidate for providing aryloxyalkanoate dioxygenase
`activity, Typically, one locking for a substitute gene would select a homolog having the
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`highest sequence identity to the gene to be replaced, and selecting a gene having low
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`sequence identity relative to the gene lo be replaced, when other genes having higher
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`sequence identity were available, would be acting contrary to conventional wisdom, in my
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`Opon.
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`iz. Although SdpA (AAD-12) had been identified at the time of the present invention as being
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`capable of catalyzing a reaction analogous to that of TRIA, no examination of other
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`herbicidal subsirates of SdpA outside of the phenoxy auxin class were reported before the
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`present invention. As 4 resull of the present invention, it was discovered that SdpA render
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`the plants resistant to one or more pyridyloxyacetate herbicides such as triclopyr and-
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`Huroxypyr. Al the timeof invention, no other o-KG dioxygenase enzymes had been
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`reported to render the plants resistant to a phonoxyacetic acid herbicide (suck as 2,4-D) and
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`one or more pyridyloxyacetate herbicides such as Wiclopyr and flurosypyr.
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`13. For the above reasons, 1 is evident to me, as one skilled in the art, that the cornbined
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`icachings of Kaphamumer in view of Schieinite et al. and Pallett et al. fail to suggest or
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`be
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`provide any guidance of how to obtain 4 gene and recombinant plant that has the
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`functionality of the present claimed invention.
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`i4, Thereby declare that all statements made herein are irue and that theyare based on my
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`own knowledge, information and belief,
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`Place and Date:
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` Indianapolis, Indiana
`nangcana
`Teny R. Wright
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`Cystinguished Laureate
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`Corteva Agriscience
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`eat
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