`
`
`
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`SYNGENTA CROP PROTECTION AG,
`Petitioner,
`
`v.
`
`UPL LIMITED,
`Patent Owner.
`
`
`
`
`
`Case PGR2023-00017
`Patent 11,445,727 B2
`
`DECLARATION OF PHILLIP M. BRANNEN, Ph.D., IN SUPPORT OF
`PETITION FOR POST-GRANT REVIEW OF U.S. PATENT NO. 11,445,727
`
`
`
`
`
`
`SYNGENTA EXHIBIT 1003
`Syngenta v. UPL, PGR2023-00017
`
`

`

`
`
`I. 
`
`TABLE OF CONTENTS
`INTRODUCTION ........................................................................................... 1 
`A. 
`Scope of Work ........................................................................................... 1 
`B. 
`Qualifications ............................................................................................ 2 
`C.  Materials Reviewed ................................................................................... 4 
`SUMMARY OF OPINIONS ........................................................................... 4 
`II. 
`III.  LEGAL STANDARDS ................................................................................... 6 
`A.  Unpatentability .......................................................................................... 6 
`B. 
`Anticipation ............................................................................................... 8 
`C. 
`Obviousness ............................................................................................... 9 
`D.  Written Description Requirement ........................................................... 11 
`E. 
`Enablement Requirement ........................................................................ 12 
`IV.  BACKGROUND OF THE TECHNOLOGY AND THE LEVEL OF
`ORDINARY SKILL IN THE ART ............................................................... 13 
`A.  General Background ................................................................................ 13 
`B. 
`The’727 Patent ......................................................................................... 18 
`CLAIM TERMS ............................................................................................ 27 
`A. 
`Fungicidal Combination and Composition ............................................. 28 
`B. 
`“Agrochemically acceptable excipient” .................................................. 29 
`VI.  Overview of prior art ..................................................................................... 29 
`A.  Godoy (Ex. 1005) .................................................................................... 29 
`B. 
`Gullino (Ex. 1010) ................................................................................... 30 
`C. 
`Tobler (Ex. 1006) .................................................................................... 32 
`D.  De Oliveira (Ex. 1007) ............................................................................ 34 
`E.  Wiglesworth (Ex. 1008) .......................................................................... 38 
`F. 
`Elatus EPA Label (Ex. 1009) .................................................................. 39 
`VII.  GROUNDS FOR UNPATENTABILITY ...................................................... 40 
`A.  Ground 1: Claims 1, 3, 4, 5, 7, 9 and 10 of the ‘727 Patent are
`anticipated by Godoy (Ex. 1005). ........................................................... 40 
`Ground 2: Claims 1-10 of the ‘727 Patent are anticipated by, or in
`the alternative rendered obvious by, Tobler (Ex. 1006) alone or in
`view of Godoy (Ex. 1005) ....................................................................... 47 
`
`V. 
`
`B. 
`
`i
`
`

`

`
`
`C. 
`
`Ground 3: Claims 1-10 of the ‘727 Patent are rendered obvious by
`De Oliveira (Ex. 1007) alone or in view of either Wiglesworth (Ex.
`1008), Tobler (Ex. 1006) or Godoy (Ex. 1005) .......................................... 67 
`D.  Ground 4: Claims 1-10 of the ‘727 Patent lack enablement .................. 82 
`VIII.  CONCLUSION .............................................................................................. 87 
`
`
`
`
`
`
`ii
`
`

`

`
`
`I, Phillip M. Brannen, hereby declare as follows:
`
`I.
`
`INTRODUCTION
`A.
`Scope of Work
`1.
`I have been retained by Baker & Hostetler LLP on behalf of Syngenta
`
`Crop Protection AG (“Syngenta” or “Petitioner”) as an independent expert to
`
`provide my opinions on the subject matter recited in U.S. Patent No. 11,445,727
`
`(Exhibit 1001, “the ‘727 Patent”) in view of the state of the art at the time and
`
`various references that predate the ‘727 Patent, all of which I refer to in this
`
`declaration.
`
`2.
`
`I understand that Syngenta is petitioning the Patent Trial and Appeal
`
`Board (PTAB) to institute a post-grant review (PGR) of the ‘727 Patent, and is
`
`requesting that the PTAB cancel each of claims 1-10 (the “Challenged claims”) as
`
`unpatentable due to lack of enablement, anticipation, and/or obviousness. I
`
`understand that this declaration is being filed as an Exhibit in the PGR.
`
`3.
`
`I make this declaration based upon personal knowledge. I am over the
`
`age of 21 and otherwise competent to make this declaration.
`
`4.
`
`I am being compensated at my normal and customary rate for work
`
`performed on this matter. My compensation does not depend on the nature of my
`
`findings, the presentation of my findings in testimony, or the outcome of this
`
`proceeding. I have no financial interest in Petitioner or Patent Owner.
`
`1
`
`

`

`
`
`B. Qualifications
`5.
`I am a Professor of Plant Pathology at the College of Agricultural and
`
`Environmental Sciences, University of Georgia.
`
`6.
`
`In 1983, I received a Bachelor of Science degree in plant protection
`
`and pest management from the University of Georgia. In 1986, I earned my Master
`
`of Science degree in plant pathology, also from the University of Georgia. In 1996,
`
`I earned my Ph.D. in plant pathology from Auburn University.
`
`7.
`
`I joined the faculty of the University of Georgia in 2000, first as an
`
`assistant professor and then as an associate professor. I was promoted to professor
`
`in 2012.
`
`8.
`
`Before becoming a faculty member at the University of Georgia, I
`
`worked in industry and in other related jobs. From 1994 to 2000, I was a plant
`
`pathologist in the Biologicals Department of Gustafson LLC in McKinney, Texas.
`
`I also worked as a county agent for the Alabama Cooperative Extension Service in
`
`the College of Agriculture of Auburn University in Alabama.
`
`9.
`
`I currently supervise three graduate students in the Plant Pathology
`
`department at the University of Georgia.
`
`10.
`
`Since 2000, I have taught numerous undergraduate and graduate level
`
`courses in plant pathology, including integrated pest management, field plant
`
`pathology, and the history of plant diseases.
`
`2
`
`

`

`
`
`11.
`
`I have extensive experience with use of fungicides and developing
`
`fungicide programs for control of plant diseases. These experiences include my
`
`time with Gustafson LLC, where I developed lab, greenhouse and field trials to
`
`review chemical fungicides and biologicals individually and in combination for
`
`disease management of seed and soil borne diseases. My experience as a plant
`
`pathologist with the University of Georgia has mainly concentrated on experiments
`
`in the field with fungicides, but I have also conducted collaborative research
`
`relative resistance management. This research has involved the review of
`
`fungicides as solo applications and in mixtures (e.g., commercial products and tank
`
`mixes). I am well aware of the additive, antagonistic, or synergistic impact of
`
`fungicides, and I have had trials reviewing such in the field.
`
`12.
`
`Over the course of my career, I have published extensively on the
`
`subject of plant pathology, including twelve book chapters, and 58 refereed articles
`
`and more than 151 peer-reviewed articles in scientific journals. In addition, I have
`
`authored a significant number of abstracts that are included in the proceedings of
`
`various scientific conferences. These publications have largely centered around the
`
`use of fungicides in solo applications and in combination for management of fungal
`
`diseases of plants.
`
`13.
`
`I have given numerous talks or presentations at various scientific
`
`conferences, providing insights on a variety of topics in the field of plant pathology.
`
`3
`
`

`

`
`
`I am also an active member in a number of professional societies and frequently lead
`
`trainings and educational programs for the American Phytopathological Society and
`
`the Southern Region Small Fruit Consortium.
`
`14.
`
`I have set forth particularly relevant qualifications to my testimony in
`
`these matters in the preceding paragraphs. Additional information regarding my
`
`background, qualifications and expertise is included in my curriculum vitae, which
`
`is attached as Appendix A.
`
`15.
`
`It is for at least the foregoing reasons that I am an expert in plant
`
`pathology with experience in disease diagnosis and management.
`
`C. Materials Reviewed
`16.
`In forming my opinions, I have reviewed the ʼ727 Patent and
`
`considered each of the documents listed in the Exhibit List appended to this
`
`declaration (Appendix B) and the other references cited in my declaration. In
`
`reaching my opinions, I have relied upon my experience in the field and also
`
`considered the viewpoint of a person of ordinary skill in the art at the time of the
`
`earliest claimed Priority Date of the ʼ727 Patent, i.e., November 2016. As explained
`
`below, I am familiar with the level of skill of a person of ordinary skill in the art
`
`regarding the relevant technology at issue as of that time.
`
`II.
`
`SUMMARY OF OPINIONS
`17.
`I have been asked to consider and provide my opinions on certain
`
`4
`
`

`

`
`
`topics related to ‘727 Patent, including:
`
`•
`
`The level of a person of ordinary skill in the art (POSA) at the time
`
`of the alleged invention described in the claims of the ‘727 Patent
`
`•
`
`How a person of ordinary skill in the art (POSA) would interpret the
`
`claims of the ‘727 Patent;
`
`•
`
`Whether any of the claims of the ‘727 Patent were anticipated by
`
`certain prior art references;
`
`•
`
`Whether any of the claims of the ‘727 Patent were obvious in view
`
`of certain prior art references; and
`
`•
`
`Whether the claims of the ‘727 Patent are enabled to their full scope.
`
`18.
`
`In forming my opinions, I reviewed the documents cited in this
`
`declaration.
`
`19. My opinions are based upon my education, training, and experience
`
`in the field of plant pathology, with an emphasis on fungicides and integrated
`
`disease management, as well as the documents I considered.
`
`20.
`
`As I discuss below in more detail, it is my opinion that:
`
`•
`
`Claims 1, 3, 4, 5, 7, 9 and 10 of the ‘727 Patent are anticipated by Godoy
`
`(Ex. 1005);
`
`•
`
`Claims 1-10 of the ‘727 Patent are anticipated by, or in the alternative
`
`rendered obvious by, Tobler (Ex. 1006) alone or in view of Godoy (Ex. 1005);
`
`5
`
`

`

`
`
`•
`
`Claims 1-10 of the ‘727 Patent are rendered obvious by WO2015079334
`
`(“De Oliveira”) (Ex. 1007) in view of either Wiglesworth (Ex. 1008), Tobler (Ex.
`
`1006) or Godoy (Ex. 1005); and
`
`•
`
`Claims 1-10 are unpatentable for lack of an enabling disclosure in the patent.
`
`III. LEGAL STANDARDS
`21. My understanding of relevant
`
`legal standards, as discussed
`
`throughout this declaration, is based on instructions from Petitioner’s counsel.
`
`22.
`
`In this section I describe my understanding of certain legal standards.
`
`I have been informed of these legal standards by Petitioner’s counsel. I am not an
`
`attorney, and I am relying only on instructions from Petitioner’s counsel for these
`
`legal standards. I have applied these understandings in my analysis as detailed
`
`below.
`
`A. Unpatentability
`23.
`I understand that patent protection may be granted for any new and
`
`useful process, machine, manufacture, or composition of matter, or any new and
`
`useful improvement thereof. I understand that a patent or other publication must
`
`first qualify as prior art before it can be used to invalidate a patent claim. I
`
`understand that the law provides categories of information that constitute prior art
`
`that may be used to anticipate or render obvious patent claims. To be prior art to a
`
`particular patent, a reference must have been made, known, used, published, or
`
`6
`
`

`

`
`
`patented, or described in a patent application by another, before the Priority Date
`
`of the patent at issue. I also understand that a POSA is presumed to have knowledge
`
`of the relevant prior art as of the Priority Date. I have reviewed the teachings of the
`
`prior art with the understanding of a POSA. I have also reviewed the ’727 Patent
`
`and relevant portions of the ‘727 Patent’s file history with this understanding.
`
`24.
`
`I understand that documents and materials that qualify as prior art can
`
`be used to render a claim unpatentable as anticipated under 35 U.S.C. § 102 or as
`
`obvious under 35 U.S.C. § 103.
`
`25.
`
`I have been told that Syngenta bears the burden of proving
`
`unpatentability by a preponderance of the evidence. I am informed that this
`
`preponderance of the evidence standard means that Syngenta must show that
`
`unpatentability is more probable than not. I have taken this principle into account
`
`when forming my opinions here.
`
`26.
`
`I understand that the ‘727 Patent issued from an application filed in
`
`the U.S. Patent & Trademark Office (USPTO) based on international application
`
`(PCT/IB2017/056710) filed on October 30, 2017. I further understand the
`
`international application claims priority back to an application filed in India (IN
`
`201631037704) on November 4, 2016. I understand that the application filed in
`
`India on November 4, 2016 is the earliest effective filing date of the ‘727 Patent,
`
`and it is the filing date I have considered for my analyses (“Priority Date”).
`
`7
`
`

`

`
`
`However, my opinions would not change even if the ‘727 Patent is determined to
`
`have an effective filing date of October 30, 2017, the filing date of the international
`
`application.
`
`27.
`
`I understand that the first step in comparing prior art to patent claims
`
`is to properly construe the claims to determine claim scope and meaning. I
`
`understand that in post-grant review proceedings, claim terms are given their
`
`ordinary and customary meaning, as understood by a person of ordinary skill in the
`
`art (POSA) in the context of the entire disclosure of the specification, as well as in
`
`view of statements made during the prosecution of the patent. I also understand that
`
`an inventor may act as his own lexicographer and define terms in the patent.
`
`28.
`
`I understand once the claims of a patent have been properly
`
`construed, the second step in determining whether or not a claim is patentable
`
`requires a comparison of the properly construed claim to the prior art.
`
`B. Anticipation
`29.
`I understand that a prior art reference “anticipates” a claim, and thus
`
`renders the claim unpatentable, if all elements of the claim were disclosed in that
`
`prior art reference, either explicitly or inherently (i.e., necessarily present or
`
`implied).
`
`30.
`
`I am told anticipation requires that each and every element of a
`
`challenged claim is present in a single reference. I also understand that an
`
`8
`
`

`

`
`
`anticipatory reference does not need to explicitly describe each element because
`
`anticipation can occur when a claimed limitation is necessarily inherent or
`
`otherwise implicit in the reference.
`
`31.
`
`I understand that a person of ordinary skill in the art provides a
`
`reference point from which the prior art and claimed invention should be viewed.
`
`C. Obviousness
`32.
`I have been informed that a claim is obvious (35 USC 103) if the
`
`differences between the subject matter sought to be patented and the prior art are
`
`such that the subject matter as a whole would have been obvious at the time the
`
`invention was made to a person having ordinary skill in the art to which said subject
`
`matter pertains.
`
`33.
`
`I have been told the determination of obviousness is resolved on the
`
`basis of several underlying factual inquiries including: (1) the scope and content of
`
`the prior art; (2) the differences between the claimed subject matter and the prior
`
`art; (3) the level of ordinary skill in the art; and (4) if in the record, objective
`
`evidence of non-obviousness.
`
`34.
`
`Such objective evidence of non-obviousness may include: (1) a long
`
`felt but unmet need in the prior art that was satisfied by the invention of the patent;
`
`(2) commercial success of processes covered by the patent; (3) unexpected results
`
`achieved by the claimed subject matter; (4) praise of the invention by others skilled
`
`9
`
`

`

`
`
`in the art; (5) taking of licenses under the patent by others; (6) deliberate copying
`
`of the invention; (7) failure of others to find a solution to the long felt need; and (8)
`
`skepticism by experts.
`
`35.
`
`I also understand that there must be a nexus between any such
`
`objective evidence of non-obviousness and the claimed subject matter. I further
`
`understand that any such objective evidence must be reasonably commensurate
`
`with the scope of the claimed subject matter.
`
`36.
`
`I have also been informed that when there is some recognized reason
`
`to solve a problem—and there are a finite number of identified, predictable, known
`
`solutions—a POSA is motivated and has good reason to pursue the known options
`
`within his or her technical grasp. If this approach leads to the expected success, it is
`
`likely the product of ordinary skill and common sense rather than the product of
`
`innovation. Where a patent simply arranges old elements, with each element
`
`performing its known function and the whole yielding no more than would be
`
`expected, the combination is obvious.
`
`37.
`
`I have also been informed that the USPTO supplies its examining
`
`corps with a Manual of Patent Examining Procedure that provides exemplary
`
`rationales that may support a conclusion of obviousness, including:
`
`(a)
`
`Combining prior art elements according to known methods to yield
`
`predictable results;
`
`10
`
`

`

`
`
`(b)
`
`Simple substitution of one known element for another to obtain
`
`predictable results;
`
`(c)
`
`Use of known technique to improve similar devices (methods, or
`
`products) in the same way;
`
`(d)
`
`Applying a known technique to a known device (method, or product)
`
`ready for improvement to yield predictable results;
`
`(e)
`
`“Obvious to try” – choosing from a finite number of identified,
`
`predictable solutions, with a reasonable expectation of success;
`
`(f)
`
`Known work in one field of endeavor may prompt variations of it for
`
`use in either the same field or a different one based on design incentives or
`
`other market forces if the variations are predictable to one of ordinary skill
`
`in the art; or
`
`(g)
`
`Some teaching, suggestion, or motivation in the prior art that would
`
`have led one of ordinary skill to modify the prior art reference or to combine
`
`prior art reference teachings to arrive at the claimed invention.
`
`MPEP § 2143. I apply these principles in my analysis below.
`
`D. Written Description Requirement
`38.
`I understand that claims of a patent are unpatentable under 35 U.S.C.
`
`§ 112 if the specification of the patent does not contain adequate written description
`
`of the invention. I have been instructed that in the patent application process, the
`
`11
`
`

`

`
`
`Applicant may keep the originally filed claims, or change the claims between the
`
`time the patent application is first filed and the time a patent is issued. An Applicant
`
`may amend the claims or add new claims. The written description requirement
`
`ensures that the issued claims correspond to the scope of the written description as
`
`provided in the original application.
`
`39.
`
`I also understand that the written description requirement is satisfied
`
`if a person having skill in the art reading the original patent application would have
`
`recognized that it describes the full scope of the claimed invention as it is finally
`
`claimed in the issued patent and that the inventor actually possessed that full scope
`
`by the filing date of the original application.
`
`40.
`
`I have been additionally instructed that the written description
`
`requirement may be satisfied by a combination of the words, figures and formulae
`
`contained in the patent application. The full scope of a claim or any particular
`
`requirement in a claim need not be expressly disclosed in the original patent
`
`application if a person of skill in the art would have understood that the full scope
`
`is in the written description in the patent application.
`
`E.
`41.
`
`Enablement Requirement
`It is my further understanding that a claimed invention is not
`
`patentable under 35 U.S.C. § 112 for lack of enablement if the specification does
`
`not contain a sufficiently full and clear description of how to make and use the full
`
`12
`
`

`

`
`
`scope of the claimed invention. In order to be enabling, the patent must permit one
`
`of skill in the art to make and use the full scope of the claimed invention at the time
`
`of original filing without having to conduct undue experimentation. In deciding
`
`whether a person having skill in the art would have to experiment unduly in order
`
`to make and use of the invention, I understand several factors may be considered:
`
`(1) the quantity of experimentation necessary, (2) the amount of direction or
`
`guidance presented, (3) the presence or absence of working examples, (4) the nature
`
`of the invention, (5) the state of the prior art, (6) the relative skill of those in the art,
`
`(7) the predictability or unpredictability of the art, and (8) the breadth of the claims.
`
`I understand that no one or more of these factors alone is dispositive. Rather,
`
`whether the degree of experimentation required is undue requires weighing these
`
`factors in the context of the claimed invention and the state of the art at the time of
`
`the original application.
`
`IV. BACKGROUND OF THE TECHNOLOGY AND THE LEVEL OF
`ORDINARY SKILL IN THE ART
`A. General Background
`42.
`Fungicides are compounds that are toxic to fungi and used to control
`
`fungal pathogens in plants. There are many commercially available fungicides;
`
`many of which are sold as products including a single fungicidal active ingredient
`
`and many of which are sold as products including a combination of fungicides. See,
`
`e.g., The Pesticide Manual (Ex. 1011); Gullino (Ex. 1010); Godoy (Ex. 1005);
`
`13
`
`

`

`
`
`Wiglesworth (Ex. 1008).
`
`43.
`
`Fungicides are typically applied as sprays of aqueous solutions by
`
`mechanical sprayers, though other means are used such as by dusting. Mechanical
`
`sprayers can range in size and scale from a backpack sprayer to large tractor-
`
`mounted boom applicators or airblast sprayers.
`
`44.
`
`Fungicides are typically categorized based on the location where they
`
`act to control fungi, e.g., whether they act “on”, or “within” the plant. For example,
`
`contact fungicides act on plants, whereas systemic fungicides act within plants.
`
`Fungicides can also be categorized based on the timing of the interaction of the
`
`fungicide with the fungus, so they are therefore listed as being preventative,
`
`curative or eradicant in nature.
`
`45.
`
`Ethylene Bis Dithiocarbamate (EBDC) fungicides, such as
`
`mancozeb, are known as contact fungicides, whereas Quinone outside Inhibiting
`
`fungicides (QoI) and Demethylation Inhibitor (DMI) fungicides are generally
`
`considered systemic fungicides. The same is true for Succinate Dehydrogenase
`
`Inhibitor (SDHI) fungicides, though the level of systemic activity may be limited
`
`in some cases. Contact fungicides are generally more likely to be removed from the
`
`plant surface by rainfall or irrigation, whereas systemic or meso-systemic
`
`fungicides, once in the plant cells, are protected from wash off.
`
`46.
`
`Fungicides control fungal disease by various modes of action – the
`
`14
`
`

`

`
`
`specific means by which a fungicidal compound disrupts fungal cellular processes.
`
`The modes of action are highly variable and range from very broad to very narrow
`
`and specific. The mode of action of a fungicide will determine its efficacy as well
`
`as whether fungi will develop resistance to the fungicide over its repeated use.
`
`47.
`
`Certain fungicides have multiple modes of action (e.g., a multisite
`
`fungicide), and fungi are not likely to develop resistance to such multisite
`
`fungicides. There are likewise fungicides with very targeted modes of action in the
`
`fungus, and for these, the fungus can often develop resistance.
`
`48.
`
`Examples of common fungicide classes with specific modes of action
`
`would include the Demethylation Inhibitors (DMIs), Quinone outside Inhibitors
`
`(QoIs), and Succinate Dehydrogenase Inhibitors (SDHIs). DMIs specifically inhibit
`
`a step in ergosterol biosynthesis. Both the QoIs and the SDHIs inhibit mitochondrial
`
`respiration, but the pathways sites are different; SDHIs interfere with the complex
`
`II while QoIs interfere with the complex III.
`
`49.
`
`Individual fungicides have been used to control fungi, but it is
`
`conventional to combine fungicides to control fungal disease. Fungicides are
`
`combined for several reasons, but primary among these are: (1) to broaden the
`
`efficacy range of the fungicidal treatment against multiple fungal pathogens; (2) for
`
`resistance management; (3) to exploit the location of action (e.g., contact and
`
`systemic); and (4) to take advantage of either additive or synergistic interactions
`
`15
`
`

`

`
`
`that increase activity, while possibly allowing for reduced fungicide rates of the
`
`individual components (see, e.g., Gisi, Ex. 1013; Levy, Ex. 1014).
`
`50.
`
`It is also well known how to determine whether a fungicidal
`
`combination acts additively or synergistically. Synergy is defined as when a
`
`combination of fungicides has an observed affect that is greater than the expected
`
`effect of the sum of the individual components (Colby, Ex. 1012; Gisi, Ex. 1013;
`
`Levy, Ex. 1014). Effects can also be antagonistic (negative interaction) or be
`
`simply additive (no interaction). Colby (Ex. 1012) is one of the primary initial
`
`documents that reviews synergy between chemical compounds when applied for
`
`agricultural purposes. While this document concentrated on herbicides (e.g.,
`
`weedkillers), the article is equally applicable to studying the additive, synergistic,
`
`and antagonistic effects of fungicides. Colby (Ex. 1012) indicated that one of the
`
`difficulties in determining synergy or antagonism is that it is essential that the
`
`compounds in question be applied singly and in combination, and most studies only
`
`look at the efficacy of the combinations.
`
`51.
`
`Depending on the number of combinations reviewed, the treatment
`
`list can become rather large, and there are statistical challenges that result from field
`
`trials with a large number of treatments. Synergy can be calculated by various
`
`methods in the lab and field (Colby, Ex. 1012; Levy, Ex. 1014; Gisi, Ex. 1013;
`
`Emery, Ex. 1016), but due to field variability, the requirement that individual
`
`16
`
`

`

`
`
`compounds be tested at the same time as the mixtures is a requirement for running
`
`trials in the field (Colby (Ex. 1012)). Factorial statistical designs can be utilized to
`
`determine significant interactions between compounds for disease control, and
`
`statistics can be performed to further determine the degree of synergy or antagonism
`
`(Emery, Ex. 1016).
`
`52.
`
`Fungicidal combinations having synergistic activity have been
`
`reported. For example, Gisi (Ex. 1013) reported that mancozeb provides strong
`
`synergistic interactions with oxadixyl fungicides. U.S. Patent 9,314,022 (Ex. 1006)
`
`reported that benzovindiflupyr (compound A-1.1) showed synergistic activity with
`
`each of azoxystrobin and cyproconazole. See U.S. Patent 9,314,022 (Ex. 1006) at
`
`Tables B2, B3, B4, B6, B7. Fungicidal combinations not having synergistic activity
`
`have also been reported. For example, Koller (Ex. 1015) found mancozeb was
`
`additive with DMI fungicides for disease control of apple scab and Emery (Ex.
`
`1016) found no synergy among two-way mixtures of propiconazole with either
`
`benomyl, captan, chlorothalonil, cyprodinil or vinclozolin in inhibiting Monilinia
`
`fructicola, the causal agent of blossom blight and brown rot of stone fruits, at low,
`
`medium and high concentrations in all possible pairwise combinations.
`
`53.
`
`Lastly, it is noted that all of the fungicides listed in the ‘727 Patent
`
`were known before the Priority Date. See, e.g., The Pesticide Manual (Ex. 1011),
`
`U.S. Patent 9,314,022 (Ex. 1006).
`
`17
`
`

`

`
`
`B.
`
`54.
`
`The’727 Patent
`1.
`Specification
`The ‘727 Patent is directed to combinations of known fungicides for
`
`use in control of fungal disease in plants. In particular, the ‘727 Patent is directed
`
`to fungicidal combinations that include: (a) a dithiocarbamate fungicide, such as
`
`mancozeb,
`
`(b) a succinate dehydrogenase
`
`inhibitor
`
`(SDHI), such as
`
`benzovindiflupyr, (c) an ergosterol biosynthesis inhibitors and/or (d) a Quinone
`
`outside inhibitor (QoI). ‘727 Patent (Ex. 1001) at 3:41-62.
`
`55.
`
`According to the ‘727 Patent, “Succinate dehydrogenase inhibitor
`
`(SDHI) fungicides are known in the art to be broad spectrum and have a high
`
`potency”. ‘727 Patent (Ex. 1001) at 1:28-30. The ‘727 Patent further discloses that
`
`“[v]arious other classes of fungicides are also known in the art, such as Quinone
`
`outside inhibitors (QoIs), ergosterol biosynthesis . . .” and that “[t]hese fungicides
`
`have been mixed with SDHI fungicides to achieve a broad spectrum of disease
`
`control”. ‘727 Patent (Ex. 1001) at 1:37-42. The ‘727 Patent continues to explain
`
`that dithiocarbamate fungicides, such as mancozeb, are known in the art and that
`
`“[m]ancozeb has been combined with various SDHI fungicides for disease control.”
`
`‘727 Patent (Ex. 1001) 1:50-62. These statements in the Background section of the
`
`‘727 Patent are consistent with the prior art descriptions of fungicides as set out in
`
`Section IV.A above.
`
`18
`
`

`

`
`
`56.
`
`The ‘727 Patent, however, discloses there “is a need in the art to
`
`improve on the disease spectrum provided by these combinations” and that “there
`
`is a need for a combination of actives that allows for broader disease control
`
`spectrum that combines curative and preventive actives and has a lower dosage”.
`
`Id at 1:62-2:4.
`
`57.
`
`As part of its embodiments, the ‘727 Patent provides “combinations
`
`of fungicides that possess an enhanced efficacy over the individual fungicides used
`
`in isolation.” ‘727 Patent (Ex. 1001) at 2:7-10. A POSA would understand from
`
`this statement that the fungicidal combinations showed synergy since the phrase
`
`“enhanced efficacy” is being equated with the definition of synergy, i.e., when the
`
`effect of the combination is greater than the individual fungicides used in isolation.1
`
`58.
`
`The ‘727 Patent then discloses Examples of commercially available
`
`fungicides which it asserts showed synergy. ‘727 Patent (Ex. 1001) at 20:15.
`
`According to the ‘727 Patent, certain combinations were tested for efficacy of
`
`disease control of Asian soybean rust and the trials were carried out at various
`
`locations in India. ‘727 Patent (Ex. 1001) at Tables 1 and 2 of the ‘727 Patent
`
`
`1 Enhanced efficacy and similar phrase are also used in the art to mean synergy.
`
`For example, Emery describes synergistic interaction as correlating with
`
`“enhanced” disease control. Emery (Ex. 1016) at p.42, left column.
`
`19
`
`

`

`
`
`provide data when mancozeb was included with other fungicides. These tables are
`
`produced below with annotations.
`
`Table 1 of ‘727 Patent (Ex. 1001 at col. 20)
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`A1
`
`A2
`
`B1
`
`B2
`
`C1
`
`C2
`
`
`
`Table 2 of ‘727 Patent (Ex. 1001 at col 21)
`
`
`
`D1
`
`D2
`
`
`
`
`
`
`
`
`
`
`
`20
`
`

`

`
`
`
`
`59.
`
`The ‘727 Patent discloses it was found that “the incorporation of
`
`mancozeb greatly increased efficacy and disease control of the succinate
`
`dehydrogenase inhibitor fungicide treatments when mixed with ergosterol
`
`biosynthesis inhibitors or quinone outside inhibitors” and concluded “that the
`
`addition of mancozeb enhanced the efficacy of the combination and surprisingly
`
`gave a synergistic effect”. ‘727 Patent (Ex. 1001) at 21:15-20; see also 20: 4-12.
`
`60. While the text of the ‘727 patent discloses mancozeb gave certain
`
`effects, the Examples and data of the ‘727 Patent do not support the alleged finding
`
`of enhanced efficacy and disease control or th