UNITED STATES PATENT AND TRADEMARK OFFICE
`_________________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_________________________
`
`
`
`E. I. DU PONT DE NEMOURS AND COMPANY and
`ARCHER-DANIELS-MIDLAND COMPANY,
`Petitioners,
`
`v.
`
`FURANIX TECHNOLOGIES B.V.,
`Patent Owner
`_________________________
`
`Case IPR2015-01838
`Patent 8,865,921
`_________________________
`
`
`
`DECLARATION OF GERT-JAN GRUTER, Ph.D.
`
`
`
`
`Exhibit 2007
`E.I. du Pont de Nemours & Co. and
`Acher-Daniels-Midland Co. v. Furanix Technologies BV
`IPR2015-01838
`
`
`_________________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_________________________
`
`
`
`E. I. DU PONT DE NEMOURS AND COMPANY and
`ARCHER-DANIELS-MIDLAND COMPANY,
`Petitioners,
`
`v.
`
`FURANIX TECHNOLOGIES B.V.,
`Patent Owner
`_________________________
`
`Case IPR2015-01838
`Patent 8,865,921
`_________________________
`
`
`
`DECLARATION OF GERT-JAN GRUTER, Ph.D.
`
`
`
`
`Exhibit 2007
`E.I. du Pont de Nemours & Co. and
`Acher-Daniels-Midland Co. v. Furanix Technologies BV
`IPR2015-01838
`
`
`
`
`
`I, Dr. Gert-Jan Gruter, hereby declare and state the following:
`
`1. I am the Chief Technology Officer for Avantium, in the Netherlands, of which
`
`Furanix Technologies, B.V. is a wholly owned subsidiary.
`
`2. I graduated from Rijksscholengemeenschap Breda in the year 1983. After
`
`two years of military service (United Nations Interim Force in Lebanon), I
`
`received a MSc degree of Organic Chemistry in 1990 from the Vrije
`
`Universiteit Amsterdam. Subsequently, I obtained my Ph.D. in the field of
`
`Organometallic Chemistry in 1994 from the same University. From 1994 to
`
`2000, I was leading a polyolefin (Polyethylene, Polypropylene and EPDM
`
`rubber) catalyst development R&D team at DSM Research in Geleen, the
`
`Netherlands (currently Sabic R&D).
`
`3. I have worked at Avantium since the start of the company in 2000. I started as
`
`Avantium’s VP Technology Chemicals, in which role I was responsible for
`
`developing Avantium’s unique parallel reactor catalyst testing platform. I was
`
`also responsible for Avantium’s contract research activities in the field of
`
`chemical catalysis. In that role, I was responsible for signing two multi-million
`
`multi-year programs with large chemical companies in the area of aromatic
`
`side-chain oxidation (1) with DSM on toluene oxidation
`
`(http://www.chemeurope.com/en/news/7947/dsm-and-avantium-announce-
`
`2
`
`
`
`research-collaboration-in-high-throughput-experimentation-for-life-science-
`
`products.html) and (2) with BP on para-xylene oxidation
`
`(https://www.avantium.com/press-releases/avantium-bp-extend-strategic-
`
`partnership/) For these two large programs, we developed oxidation catalyst
`
`testing equipment with 96 parallel stirred autoclaves in which we conducted
`
`more than 50,000 experiments in the area of aromatic side-chain oxidation.
`
`4. In 2004, I was appointed as Chief Technology Officer (CTO). One of my main
`
`responsibilities was to initiate and lead Avantium’s own product and process
`
`development. In 2004-2005, I initiated Avantium’s research program to
`
`convert carbohydrates into furans such as 5-hydroxymethyl furfural (HMF) and
`
`5-methoxymethylfurfural (MMF), and subsequent oxidation to 2,5-furan
`
`dicarboxylic acid (FDCA), which Avantium is currently commercializing. From
`
`2004 to today, I have been intimately involved in oxidation research at the
`
`Avantium labs in Amsterdam. I have 15 years of experience in researching,
`
`developing and conducting oxidation reactions involving aromatic compounds.
`
`5. I am a named inventor on numerous patents and applications, including U.S.
`
`Patent No. 8,865,921 (“the ‘921 patent,” Exhibit 1001 or Ex. 1001) that is the
`
`subject of this IPR proceeding. A copy of my curriculum vitae is included with
`
`this declaration as Exhibit 2008 (“Ex. 2008, c.v. of Dr. Gruter). I understand
`
`that this declaration itself has been designated for this IPR as Exhibit 2007
`
`3
`
`
`
`(“Ex. 2007,” Declaration of Dr. Gert-Jan Gruter).
`
`6. I am not being compensated for preparing this declaration in any respect
`
`beyond my regular salary associated with my employment at Avantium.
`
`7. In 2008-2009, I was leading the research team at Avantium. In that role, I was
`
`intimately involved in the design and execution of the oxidation reaction
`
`experiments shown in Examples 1, 2 and 3 and Tables 1, 2 and 3 of the ‘921
`
`patent for producing 2,5-furandicarboxylic acid (“FDCA”), as described in
`
`more detail below in this declaration. These procedures and results of these
`
`2008-2009 experiments are presented in Examples 1, 2 and 3 and Tables 1, 2
`
`and 3 of the ‘921 patent. See the ‘921 patent (Ex. 1001) 6:7 to 7:59.1
`
`8. In 2016, I designed and participated in additional oxidation experiments for
`
`producing FDCA, as described in more detail below in this declaration. These
`
`2016 experiments were done for this IPR and were done in accordance with the
`
`procedures set forth in Example 1 and Table 1 of the ‘921 patent. The 2016
`
`experiments show the oxidation of 5-hydroxymethyl-furfural (“HMF”) alone, as
`
`well as oxidation of mixtures of HMF and an ester of HMF(5-acetoxymethyl-
`
`furfural or “AMF”) to produce FDCA, at temperatures of 145 ºC, 160 ºC, 180
`
`ºC and 195 ºC.
`
`With regard to any references cited, in the notation X:Y, “X” is the column
`1
`
`number and “Y” is the line. If there are no columns, the “X” is the page number.
`
`4
`
`
`
`9. The 2008-2009 and 2016 oxidation experiments show unexpectedly improved
`
`yields for the FDCA end product, as compared to processes for making FDCA
`
`in the prior art to the ‘921 patent, using a similar homogeneous catalyst system.
`
`This is particularly true relative to the process in WO/0172732A2 (“the ‘732
`
`publication,” Ex. 1002), which I understand the Petitioners in this IPR have
`
`asserted is the closest prior art to the claims of the ‘921 patent at issue.
`
`
`
`FDCA History and Background
`
`10. As described in the background of the ‘921 patent, the organic compound
`
`FDCA was first obtained in 1876. See the ‘921 patent (Ex. 1001), 1:30-32.
`
`Over 125 years later, the US Department of Energy identified FDCA as one of
`
`12 priority chemicals for establishing the “green” chemistry industry of the
`
`future. See the ‘921 patent (Ex. 1001), 1:34-35, referring to Top Value Added
`
`Chemicals from Biomass, U.S. Dept. of Energy (August 2004) (Ex. 2005), also
`
`cited at (http://www.nrel.gov/docs/fy04osti/35523.pdf. HMF is a starting
`
`material for making FDCA through an oxidation reaction, and HMF is
`
`obtainable from carbohydrate containing sources such as glucose, fructose,
`
`sucrose and starch. See the ‘921 patent (Ex. 1001), 1: 38-42 and 3:1-29.
`
`11. In addition to identifying FDCA as one of 12 priority chemicals for
`
`establishing the green chemical industry, the above US Department of Energy
`
`5
`
`
`
`report from 2004 (Ex. 2005) also acknowledged that “R&D to develop
`
`selective oxidation and dehydration technology needs to be carried out.” 2004
`
`U.S. Dept. of Energy Report (Ex. 2005) at 28. In Table 13 of this report the
`
`oxidation to produce FDCA is reported as a “Technical Barrier.” 2004 U.S.
`
`Dept. of Energy Report (Ex. 2005) at 26. Paragraph 9.2.4 of this report states:
`
`“FDCA formation will require development of cost effective and industrially
`
`viable oxidation technology that can operate in concert with the necessary
`
`dehydration processes.” 2004 U.S. Dept. of Energy Report (Ex. 2005) at 28.
`
`12. Likewise, other literature from the 2004 time period noted that a commercially
`
`viable process had not been created for making FDCA. In Moreau et al.,
`
`Recent catalytic advances in the chemistry of substituted furans from
`
`carbohydrates and in the ensuing polymers, Topics in Catalysts, Vol. 27, Nos.
`
`1-4, 11-30, February 2004, (“Moreau et al.,” Ex. 1020) it is stated that:
`
`“Among the more recent papers, the air oxidation of 5-hydroxymethylfurfural
`
`with metal/bromide catalysts has been mentioned. Although those catalysts
`
`have the advantage of being industrially used in related oxidation reactions, the
`
`air oxidation of 5-hydroxymethylfurfural over this kind of catalysts only leads
`
`to a 60% yield in 2,5- furandicarboxylic acid, and under relatively severe
`
`operating conditions, 3 h at 125 ºC and air pressure of 7MPa [84]. Ref 84 = [84]
`
`W. Partenheimer and V.V. Grushin, Adv. Synth. Catal. 343 (2001) 102. (=EX
`
`6
`
`
`
`1003) ” Moreau et al. (Ex. 1020) at 18.
`
`13. Even five years later, in 2009 the scientific FDCA literature was reporting
`
`that “[i]n spite of all the research carried out within this area an efficient way
`
`producing HMF or its corresponding dicarboxylic acid, FDA [i.e., FDCA], still
`
`remains to be found.” Boisen et al., Process integration for the conversion of
`
`glucose to 2,5-furandicarboxylic acid, 87 Chemical Engineering Research and
`
`Design,1318-1327 (2009) (“Boesen et al., Ex. 2006) at 1320. That same
`
`reference also concludes that “it is clear that new technology and improved
`
`catalytic methods are required to produce high value building blocks such as
`
`FDA.” Id. (Ex. 2006) at 1325.
`
`14. Finally, US2015/0183755 (“the ‘755 publication, assigned to ADM, Ex.
`
`2004), which was filed in August, 2011 (as a provisional application) and
`
`published in 2015, states: “Unfortunately, while HMF and its oxidation-based
`
`derivatives such as FDCA have thus long been considered as promising
`
`biobased starting materials, intermediates and final products for a variety of
`
`applications, viable commercial-scale processes have proven elusive”. The
`
`‘755 publication (Ex.2004) at paragraph [0006].
`
`15. Thus, while the compound FDCA, and beneficial ways in which it might be
`
`used, were known prior to the ‘921 patent, no one had created a commercially
`
`viable process to prepare FDCA efficiently and in high yields, so that its
`
`7
`
`
`
`benefits could be realized. There was a well-known and long-felt need for a
`
`solution to that problem, which I solved with my co-inventors, Cesar Munoz De
`
`Diego and Matheus Adrianus Dam, when we developed the FDCA processes of
`
`the ‘921 patent. In particular, we developed a process for oxidizing a feed
`
`stream comprising a compound selected from the group consisting of HMF, an
`
`ester of HMF, 5-methylfurfural (“5-MF”), 5-(chloromethyl)furfural, 5-
`
`methylfuroic acid, 5-(chloromethyl)furoic acid, 2,5-dimethylfuran (“DMF”) and
`
`a mixture of two or more of these compounds. Claims 1-5 recite critical
`
`parameters of the invention, including oxidizing in the presence of a Co/Mn/Br
`
`catalyst, at a temperature between 140 ºC and 200 ºC, at an oxygen partial
`
`pressure of 1 to 10 bar, and using an acetic acid solvent or water/acetic acid
`
`solvent mixture.
`
`16. During our research, we evaluated the degradation of FDCA at high
`
`temperatures, including above 200 ⁰C in May and June of 2009. Our
`
`experiments in this regard art set forth in Electronic Notebook OxE-073
`
`(Exhibit 2016) at 1-4 and Lab Journal OxE-073 (Exhibit 2017) at 60-61, which
`
`set forth the procedure of raising the temperature of the FDCA to 220 ºC to test
`
`whether degradation occurs at that temperature. See id. The Lab Journal OxE-
`
`073 belongs to Andre van de Beek and the Electronic Notebook OxE-073 is a
`
`document I and my colleagues sent to Mr. van de Beek at that time to have him
`
`8
`
`
`
`carry out the degradation experiments. Our results of these experiments are set
`
`forth in a set of slides put together in June 2009 by my co-inventor Ceasar de
`
`Diego and Mr. van de Beek (“the 2009 Degradation Slides,” Exhibit 2018),
`
`which show that the FDCA reaction product is unstable at temperatures of 200-
`
`220 ºC. The 2009 Degradation Slides (Ex. 2018) at 6. This degradation is
`
`confirmed by ADM’s own, later filed and published document in US
`
`2015/0183755 (“the 755 publication, Ex. 2004), for example in Tables 3 and 7
`
`of that document, and in the statements: “(…) the yield of FDCA was
`
`maximized in the 180-190 deg. C range”[0064] and “The reaction becomes less
`
`productive with further increase of the temperature to 220° C (…)”[0075]. On
`
`the other end of the temperature spectrum, we evaluated the appropriate lower
`
`limit based on yields decreasing below 140 ºC, reaction times increasing below
`
`140 ºC, and levels of intermediates such as FFCA increasing (making
`
`purification more challenging). From a process point of view, temperatures
`
`below 140 ºC would make evaporative cooling difficult (boiling of solvent and
`
`condensation/flowback provides cooling for these highly exothermic reactions).
`
`In this regard, we developed a temperature range for our invention, which was
`
`critical to the unexpectedly high FDCA yields that are realized across the scope
`
`of that range.
`
`9
`
`
`
`17. An advantage of FDCA is that it can be used as a replacement for
`
`terephthalic acid (TA), a petroleum-based monomer that is primarily used to
`
`produce PET (polyethylene-terephthalate). The FDCA monomer can be used to
`
`create a wide range of polymers, such as polyesters, polyamides and
`
`polyurethanes, as well as coating resins, plasticizers and other chemical
`
`products. At Avantium, we have been and are polymerizing FDCA with MEG
`
`(ethylene glycol) to make the polyester called PEF (polyethylene-furanoate),
`
`which is under development to be used to create bottles, films and fibers.
`
`18. At Avantium we were the first to identify that PEF is a polyester that offers
`
`superior barrier and mechanical properties, making it an ideal material for the
`
`packaging of soft drinks, water, alcoholic beverages such as beer, fruit juices,
`
`food and non-food products. PEF is a 100% bio-based alternative to PET. PEF
`
`is made from plant-based sugars. Therefore, it is renewable and does not rely
`
`on carbon derived from fossil feedstock but is made from plants. At Avantium,
`
`we are working in collaboration with partners such as The Coca Cola Company,
`
`Danone and ALPLA to bring 100% bio-based PEF bottles to the market.
`
`19. PEF can replace PET in typical applications like films, fibers and especially
`
`bottles for the packaging of soft drinks, water, alcoholic beverages, fruit juices
`
`food and non-food products. At Avantium, our goal is to develop products
`
`from renewable sources that compete on price and performance, with a superior
`
`10
`
`
`
`environmental footprint. FDCA can be used as a chemical building block in a
`
`wide variety of industrial applications to produce bio-based products and fuels
`
`with superior properties at market competitive prices, enabling this green way
`
`of doing business.
`
`20. At Avantium, we have shown that PEF bottles outperform PET bottles in
`
`many areas, particularly barrier properties (the ability of the polymer to
`
`withstand gas permeability through the bottle). PEF’s ability to seal in CO2 and
`
`to seal out oxygen, for example, results in longer-lasting carbonated drinks and
`
`thus in an extended shelf life. Moreover, PEF makes certain packaging coatings
`
`redundant, like the coatings used on bottles to keep beer fresh (oxygen barrier
`
`coatings). With regard to thermal properties, PEF is widely considered more
`
`attractive than PET due to its superior ability to withstand heat (expressed in the
`
`higher glass transition temperature or Tg versus PET) and process-ability at
`
`lower temperatures (expressed in the lower melting temperature or Tm versus
`
`PET).
`
`21. At Avantium, we also have demonstrated that PEF can be recycled in very
`
`similar ways to PET recycling. Avantium is closely collaborating with the
`
`recycling community to find the optimum end-of-life solutions for PEF.
`
`Technical data demonstrates that PEF to PEF recycling is viable, but during a
`
`transition period PEF will be mixed in the recycled PET stream. Avantium is
`
`11
`
`
`
`currently working with brand owners and the recycling industry to further
`
`integrate PEF into the PET recycling stream. Once PEF is produced in larger
`
`volumes than today, PEF will be separately recycled as it will be more
`
`economically attractive at that time. Avantium is currently working with brand
`
`owners and the recycling industry to establish a PEF to PEF recycling
`
`infrastructure in the future.
`
`
`
`The 2008-2009 Experiments Shown in the ‘921 Patent:
`
`22. At Avantium, we began working on new processes for making FDCA in the
`
`2000s to develop a viable process for effectively producing commercial
`
`quantities of FDCA in high yields, so that its useful properties could be utilized
`
`in industrial applications. I worked with the other inventors named on the ‘921
`
`patent, Cesar Munoz De Diego and Matheus Adrianus Dam. Our research
`
`efforts started with evaluating almost all known oxidation catalyst systems (e.g,
`
`Au, Pd, Ru, Pt etc. on various supports), oxidants (air, lean air, oxygen,
`
`peroxide, etc.) and methodologies (e.g., N-hydroxyimides agents, oxidative
`
`esterification to the dimethyl ester of FDCA, etc.) all typically at temperatures
`
`below or around 100°C. We studied, for example, the well-known Pt/C catalyst
`
`that gives high FDCA yields from HMF in oxidations with oxygen as oxidant in
`
`water at 70°, but according to our evaluations this process could not be scaled to
`
`12
`
`
`
`a commercially viable process due to catalyst deactivation and stoichiometric
`
`base addition/ stoichiometric salt formation in this process.
`
`23. As part of our efforts in September of 2009, we performed the experiments
`
`shown in Examples 1-3 and Tables 1-3 of the ‘921 patent. These experiments
`
`were carried out in parallel 8 ml magnetically stirred stainless steel batch
`
`reactors with Teflon liners. The reactors were grouped in blocks containing 12
`
`batch reactors. I planned these experiments with my co-inventors and asked our
`
`lab technician, Andre van de Beek, to carry them out for us. The experiments
`
`of Experiments 1 and 3 and Tables 1 and 3 of the ‘921 patent were designated
`
`OxE-081. Exhibit 2009, entitled Experiment: OxE-081, comprises the
`
`electronic notebook pages that I sent to Mr. van de Beek describing those
`
`oxidation reactions that I asked him to carry out in early September 2009.
`
`Electronic Notebook OxE-081 (Ex. 2009) at 1. As shown in that document, the
`
`“Target” of the experiments was the oxidation of HMF, AMF and mixtures of
`
`HMF/AMF, with some parameters fixed, including the temperature at 180 ºC
`
`and the air pressure at 20 bar. Electronic Notebook OxE-081 (Ex. 2009) at 1.
`
`That document also shows our plan to carry out the experiments of Example 3
`
`and Table 3 of the ‘921 patent, starting with 5-MF and DMF as the feed. See
`
`id. at 4-5. Mr. van de Beek carried out all of these experiments at my direction.
`
`For example, Mr. van de Beek’s laboratory notebook dated September 10, 2009
`
`13
`
`
`
`shows the protocol for carrying out the experiments of Example 1 and Table 1
`
`of the ‘921 patent (oxidizing HMF, AMF and HMF/AMF mixtures at 180 ºC)
`
`and the carrying out of the experiments of Example 3 and Table 3 of the
`
`‘(oxidizing 5-MF and DMF at 180 ºC). 2009 van de Beek Lab Journal (Ex.
`
`2010) at 148-49. I had first-hand knowledge of all of this work at the time
`
`developed the experiments and considered and evaluated the results. The test
`
`data and results from the ‘921 patent and the recent tests from May of 2016 are
`
`being presented to show the unexpectedly high FDCA yields achieved using the
`
`claimed processes. The way in which these tests were performed and the data
`
`that were generated is explained throughout this declaration. The data from the
`
`oxidation tests is used to generate a FDCA yield percentage using HPLC or
`
`UPLC, as explained in this declaration. These sorts of tests, data and results are
`
`regarded in the art as showing yield of FDCA, which indicates the efficiency
`
`and commercial viability of the process.
`
`24. The following procedure was followed for all of the oxidation reactions and
`
`HPLC results, with the variables and results for each experiment set forth
`
`separately in Table A below. This procedure is written with respect Experiment
`
`1a, but the exact same procedure was used for each of the experiments in
`
`Examples 1-3 and Tables 1-3, except that certain variables (e.g., temperature,
`
`reaction time, air pressure, etc.) are changed with each experiment and results
`
`14
`
`
`
`change (e.g., yield of FDCA) as noted in the Table A below. The experiments
`
`2a and 2b were done for comparative purposes, as those experiments were
`
`directed to a prior art process of U.S. Patent Publication 2009/0156841(“the
`
`‘841 publication,” Ex. 1022). For experiments 2a and 2b, I worked with my co-
`
`inventor Dr. De Diego and model the experiments after the ‘841 publication and
`
`carry them out according to that publication.
`
`25. With respect to Experiment 1a, 0.5 ml of starting material stock solution
`
`(HMF – Starting Materal) in acetic acid (0.78 mmol/ml) was added into a
`
`reactor lined with a Teflon insert. To the reactor 1 ml of a catalyst stock
`
`solution in acetic acid was subsequently added. The catalyst composition was
`
`composed of Co(OAc)2*4H2O as a Co source, Mn(OAc)2*4H2O as a Mn
`
`source, and NaBr as a Br source. The relative ratio of Co/Mn/Br was as
`
`disclosed in columns 3, 4 and 5 of Table A. The reactors were closed with a
`
`rubber septum, after which the reactors were sealed and pressurized to the
`
`desired air pressure. After pressurization to 20 bar, the block with 12 reactors
`
`was placed in the test unit which was preheated at the desired temperature of
`
`180 C. After the desired reaction time of 1 hour, the block was placed into an
`
`ice bath for 20 minutes. When the block had cooled down, it was
`
`depressurized.
`
`15
`
`
`
`26. After opening, HPLC samples were prepared. First 5 ml of a saccharine
`
`solution in DMSO (11.04 mg/ml) was added to each reactor and the mixture
`
`was stirred for 5 minutes. Then 10 µl of this mixture was diluted to 1000 µl
`
`with water in a HPLC vial. The samples were analyzed using HPLC, using the
`
`equipment set forth in Table 2: Apparatus in Ex. 2009. Electronic Notebook
`
`OxE-081 (Ex. 2009) at 1. Using HPLC and that equipment, we determined a
`
`yield of FDCA in Experiment 1a of 76.66%. As shown in the HPLC equipment
`
`logbook (Exhibit 2011), we carried out the HPLC for all of the experiments
`
`associated with OxE-081 in September of 2009. See HPLC Equipment
`
`Logbook (Ex. 2011) at 39.
`
`27. As mentioned above, in September 2009, the identical oxidation procedures
`
`(with the variables set forth in Table A) and the identical HPLC procedures
`
`were carried out for the remaining experiments associated with Examples 1-3
`
`and Tables 1-3, as reflected the entries in Table A.
`
`28. The headings for the 12 columns in Table A after the first column for the
`
`Experiment Number (abbreviated “Exp. ”) are themselves numbered 1 through
`
`12 and show the following information:
`
`1 – Starting Material
`
`2 - Co catalyst (relative to substrate) (mol %)
`
`3 - Co/Mn molar ratio
`
`16
`
`
`
`4 - Catalyst concentration (Co+Mn) (mol %)
`
`5 – Br/(Co+Mn) molar ratio
`
`6- Substrate concentration in acetic acid (wt %)
`
`7 - Air pressure (bar)
`
`8 - Temperature (°C)
`
`9 - Reaction time (hours)
`
`10 - O2/substrate (mol/mol)
`
`11 – Conversion (%)
`
`12 - s FDCA (%) – i.e., Yield of FDCA
`
`
`
`17
`
`
`
`Exp.
`
`1a
`
`1b
`
`1c
`
`1d
`
`1
`
`HMF
`
`HMF/AMF
`(molar
`ratio): 3/2
`HMF/AMF
`(molar
`ratio): 2/3
`AMF
`
`2
`
`2.7
`
`2.7
`
`3
`
`1/1
`
`1/1
`
`4
`
`5.4
`
`5.4
`
`2.7
`
`1/1
`
`5.4
`
`2.7
`
`1/1
`
`5.4
`
`5
`
`1
`
`1
`
`1
`
`1
`
`6
`
`3.3
` (0.26 M)
`3.8
` (0.26 M)
`
`4.0
` (0.26 M)
`
`5.4
`
`0.7
`
`7
`
`20
`
`20
`
`20
`
`20
`
`20
`
`8
`
`180
`
`180
`
`180
`
`180
`
`180
`
`9
`
`1
`
`1
`
`1
`
`1
`
`1
`
`10
`
`11
`
`12
`
`2.69
`
`100.00 76.66
`
`2.69
`
`100.00 71.19
`
`2.69
`
`100.00 77.66
`
`2.69
`
`100.00 64.82
`
`2.69
`
`100.00 78.08
`
`1e
`
`1f
`
`1g
`
`1h
`
`1i
`
`1j
`
`
`
`HMF
`
`HMF/AMF
`(molar
`ratio): 3/2
`HMF/AMF
`(molar
`ratio): 2/3
`AMF
`
`HMF
`
`HMF/AMF
`(molar
`ratio): 3/2
`
`2.7
`
`2.7
`
`1/1
`
`1/1
`
`5.4
`
`0.7
`
`2.7
`
`1/1
`
`5.4
`
`0.7
`
`1/1
`
`1/1
`
`1/1
`
`5.4
`
`0.7
`
`5.4
`
`0.4
`
`5.4
`
`0.4
`
`2.7
`
`2.7
`
`2.7
`
`
`
`4.4
` (0.26 M)
`3.3
` (0.26 M)
`3.8
` (0.26 M)
`
`4.0
` (0.26 M)
`
`4.4
` (0.26 M)
`3.3
` (0.26 M)
`3.8
` (0.26 M)
`
`18
`
`20
`
`20
`
`20
`
`20
`
`20
`
`180
`
`180
`
`180
`
`180
`
`180
`
`1
`
`1
`
`1
`
`1
`
`1
`
`2.69
`
`100.00 66.96
`
`2.69
`
`100.00 75.14
`
`2.69
`
`100.00 60.64
`
`2.69
`
`100.00 73.27
`
`2.69
`
`100.00 65.67
`
`
`
`Exp.
`
`1k
`
`1l
`
`1m
`
`1n
`
`1
`
`2
`
`3
`
`4
`
`5
`
`6
`
`HMF/AMF
`(molar
`ratio): 2/3
`AMF
`
`HMF
`
`2.7
`
`1/1
`
`5.4
`
`0.4
`
`2.7
`
`2.7
`
`2.7
`
`1/1
`
`1/1
`
`1/1
`
`5.4
`
`0.4
`
`5.4
`
`0.1
`
`5.4
`
`0.1
`
`5.4
`
`0.1
`
`4.0
`(0.26 M)
`
`4.4
` (0.26 M)
`3.3
` (0.26 M)
`3.8
` (0.26 M)
`
`7
`
`20
`
`20
`
`20
`
`20
`
`20
`
`8
`
`180
`
`180
`
`180
`
`180
`
`180
`
`9
`
`1
`
`1
`
`1
`
`1
`
`1
`
`10
`
`2.69
`
`11
`
`12
`
`100.00 73.21
`
`2.69
`
`100.00 57.36
`
`2.69
`
`100.00 67.92
`
`2.69
`
`100.00 60.92
`
`2.69
`
`100.00 69.64
`
`HMF/AMF
`(molar
`ratio): 3/2
`HMF/AMF
`(molar
`ratio): 2/3
`AMF
`
`AMF
`AMF
`5-MF
`
`5-MF
`
`DMF
`
`DMF
`
`1o
`
`1p
`
`2a
`2b
`3a
`
`3b
`
`3c
`
`3d
`
`
`
`2.7
`
`1/1
`
`1/1
`
`1/1
`1/1
`1/1
`
`1/1
`
`1/1
`
`1/1
`
`5.4
`
`0.1
`
`3.5
`5.3
`5.4
`
`1
`1
`1
`
`5.4
`
`0.7
`
`5.4
`
`1
`
`5.4
`
`0.7
`
`2.7
`
`1.75
`2.65
`2.7
`
`2.7
`
`2.7
`
`2.7
`
`
`
`4.0
` (0.26 M)
`
`4.4
` (0.26 M)
`10.0
`10.0
`2.9
`(0.26 M)
`2.9
`(0.26 M)
`2.5
` (0.26 M)
`2.5
`(0.26 M)
`
`19
`
`20
`
`30
`30
`50
`
`50
`
`50
`
`50
`
`180
`
`100
`100
`180
`
`180
`
`180
`
`180
`
`1
`
`2
`2
`1
`
`1
`
`1
`
`1
`
`2.69
`
`100.00 46.85
`
`2.88
`2.88
`6.7
`
`100.00 23.48
`100.00 29.05
`100.00 42.62
`
`6.7
`
`6.7
`
`6.7
`
`100.00 39.94
`
`100.00 16.17
`
`100.00 14.09
`
`
`
`Exp.
`
`1
`
`3e
`
`3f
`
`DMF
`
`DMF
`
`
`TABLE A
`
`2
`
`2.7
`
`2.7
`
`3
`
`1/1
`
`1/1
`
`4
`
`5
`
`6
`
`5.4
`
`0.4
`
`5.4
`
`0.1
`
`2.5
` (0.26 M)
`2.5
`(0.26 M)
`
`7
`
`50
`
`50
`
`8
`
`180
`
`180
`
`9
`
`1
`
`1
`
`10
`
`6.7
`
`6.7
`
`11
`
`12
`
`100.00 11.30
`
`100.00
`
`7.19
`
`
`
`20
`
`
`
`29. On September 10, 2009, my co-inventor Dr. de Diego prepared slides
`
`showing the results of our work in carrying out the experiments that are shown
`
`in Example 1 and Table 1 of the ‘921 patent (HMF, AMF and HMF/AMF
`
`oxidation). See de Diego HMF/AMF slides (Exhibit 2012). Included in these
`
`slides is a graphical presentation of the FDCA yields for the experiments of
`
`Example 1 and Table 1 of the ‘921 patent, carried out as described above and in
`
`Table A, showing the unexpectedly high FDCA yields using the process of the
`
`claims in that patent. de Diego HMF/AMF slides (Ex. 2012) at 7.
`
`30. Also on September 10, 2009, my co-inventor Dr. de Diego prepared another
`
`set of slides showing the results of our work in carrying out the experiments
`
`that are shown in Example 2 and Table 2 of the ‘921 patent (recreating the ‘841
`
`publication experiments, as above) and Example 3 and Table 3 of the ‘921
`
`patent (oxidizing 5-MF and DMF). See de Diego 841/5-MF/DMF slides
`
`(Exhibit 2013). Included in these slides is a graphical presentation of the
`
`FDCA yields for the experiments of Example 2 and Table 2 of the ‘921 patent,
`
`carried out as described above and in Table A, showing that the actual FDCA
`
`yields are as reported in Table 2 of the ‘921 patent (at most, 29%) for the ‘841
`
`publication’s process, which is lower than the 54% yield reported in that
`
`publication. de Diego ‘841/5-MF/DMF slides (Ex. 2013) at 3-4. Also
`
`included in these slides is a graphical presentation of the FDCA yields for the
`
`21
`
`
`
`experiments of Example 3 and Table 3 of the ‘921 patent, carried out as
`
`described above and in Table A, showing that the FDCA yields are as reported
`
`in Table 3 of the ‘921 patent for the oxidation of 5-MF (up to 42%) and DMF
`
`(up to 16.17%). de Diego ‘841/5-MF/DMF slides (Ex. 2013) at 6.
`
`
`
`The 2016 Experiments:
`
`31. In May of 2016, as part of this IPR proceeding, I planned and reproduced the
`
`experiments of Example 1 and Table 1 of the ‘921 patent (each of which was
`
`carried out at 180 ºC), and I then planned and further extend those experiments
`
`to additional temperatures from the range between 140 ºC and 200 ºC, namely
`
`145 ºC, 160 ºC and 195 ºC. I designed and planned these experiments and
`
`worked with my laboratory technician Danny van Kool )(DVK), and my
`
`colleagues Jan Hendrik Blank and Ana de Sousa Dias, to carry them out and
`
`analyze the resulting reaction product mixtures using the same equipment and
`
`methods that were used in the 2008-2009 experiments described above. The
`
`laboratory notebooks showing these experiments are submitted with this
`
`declaration as Exhibit 2014 (Lab Journal AM1630, dated May 3, 2016) and
`
`Exhibit 2015 (Lab Journal AM1633, dated May 9, 2016).
`
`32. All of the experiments were performed using a “QCS” multi reactor batch
`
`reactor system as was used for the experiments of the ‘921 patent. Each reactor
`
`22
`
`
`
`block has 12 individually stirred batch reactors. Prior to experimentation a
`
`temperature test was performed to ensure the correct temperature settings to
`
`achieve the correct internal temperature of the reactor. This was done by
`
`loading the reactor block with equi-volumous amounts of the solvent and
`
`calibrating the temperature settings. Lab Journal AM1630 (Ex. 2014) at 3.
`
`33. All experiments were performed by fitting the Teflon lined 8 mL reactors
`
`with a stirrer. The reactors were loaded with 0.5 mL of substrate solution
`
`containing HMF and/or HMF and AMF as well as 1 mL of catalyst solution.
`
`The concentrations of the solutions are shown in Tables 1 and 2 below. The first
`
`set of experiments was performed at 180 °C and served to benchmark the
`
`procedure and validate the replications of results in the patent. Lab Journal
`
`AM1630 (Ex. 2014) at 1. The second set of experiments was performed after
`
`assessment of the 180 °C experiments at 145 °C, 160 °C and 195 °C. Lab
`
`Journal AM1630 (Ex. 2014) at 4-7; Lab Journal AM1633 (Ex. 2015) at 1-3.
`
`Tables 1a and 1b, below, set forth the make up for solutions in the first set of
`
`experiments, and Tables 2a and 2b, below, set forth the make up for solutions in
`
`the second set of experiments.
`
`23
`
`
`
`
`Tables 1a and 1b. Make-up for solutions A, B, C and CAT for the first set of
`experiments (performed at 180 °C) .
`
` Solutions: HMF (g)
`A
`0.50277
`B
`0.30242
`C
`0.20197
`
`
`AMF (g)
`0
`0.26833
`0.39981
`
`Acetic acid
`(mL)
`5
`5
`5
`
`
`
`Co(AcO)2
`4H2O (mg)
`66.830
`
`Mn(AcO)2
`4H2O (mg) NaBr (mg)
`65.500
`55.28
`
`
`CAT
`
`AcOH
`(mL to
`mark)
`25
`
`
`
`Tables 2a and 2b. make-up for solutions A, B, C and CAT for the second set of
`experiments (all other experiments).
`AMF (g) Acetic acid
` Solutions:
`HMF (g)
`(mL)
`A
`5.09065
`50
`
`B
`2.94856
`2.65379
`50
`3.95063
`C
`1.96407
`50
`
`
`Co(AcO)2
`4H2O (mg)
`266.79
`
`Mn(AcO)2 4H2O
`(mg)
`264.79
`
`NaBr
`(mg)
`220.7
`
`AcOH
`(to mark)
`100
`
`
`
` CAT
`
`
`
`34. After the reactor vessels were loaded, the lid was screwed in place and 20 bar
`
`of air pressure was supplied to each reactor. The heating block was preheated to
`
`the target temperature using the calibrated settings. The reactor blocks were
`
`inserted into the heated block and allowed to react for 0.5, 1.0 or 2.0 hour
`
`24
`
`
`
`duration after which the reactor block was removed from heating and rapidly
`
`cooled in an iced bath. Lab Journal AM1630 (Ex. 2014) at 1, 4-6; Lab Journal
`
`AM1633 (Ex. 2015) at 1-2. All reactions were performed 4 times. See id. After
`
`cooling, the reactors were depressurized and the reactor contents were inspected
`
`and analyzed by HPLC (UPLC) analysis. The analytical procedure for such
`
`UPLC analysis and the indication of the carrying out of that procedure is set
`
`forth in Lab Journal AM1630 (Ex. 2014) at 2.
`
`
`35. Results
`
` Analysis showed a consistent problem with a single reactor vessel location.
`
`Further investigation revealed a blockage of the pressuring syringe responsible for
`
`feeding air pressure to that particular reactor location. After fixing the problem
`
`normal reactivity was observed. All results from reactions performed at that
`
`position prior to fixing the problem were therefore discarded as failed experiments.
`
`These experiments are reported in red color below.
`
` Table 3 shows the FDCA and FFCA yields (mol% per mol substrate) for each
`
`reaction together with the substrate solution used and temperature, as set forth in
`
`Ex. 2014 and Ex. 2015. The reactions shown in red indicate failed experiments of
`
`which the data was discarded from further data processing.
`
`
`
`Table 3. The complete dataset of the obtained yields and the conditions
`
`25
`
`
`
`whereunder the results have been obtained.
`
`sample ID.
`AM1630-
`Run01-R01
`AM1630-
`Run01-R07
`AM1630-
`Run01-R08
`AM1630-
`Run01-R10
`AM1630-
`Run01-R02
`AM1630-
`Run01-R05
`AM1630-
`Run01-R11
`AM1630-
`Run01-R12
`AM1630-
`Run01-R03
`AM1630-
`Run01-R04
`AM1630-
`Run01-R06
`AM1630-
`Run01-R09
`AM1630-R01-
`R13
`AM1630-R01-
`R19
`AM1630-R01-
`R20
`AM1630-R01-
`R22
`AM1630-R01-
`R14
`AM1630-R01-
`R17
`
`FDCA
`yields
`
`FFCA
`yields T (oC)
`
`time
`(Hr) Substrate
`
`63.7486 13.50957 180
`
`76.77926
`
`77.72321
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