`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`COMMONWEALTH SCIENTIFIC AND INDUSTRIAL RESEARCH
`ORGANISATION,
`Petitioner,
`
`v.
`BASF PLANT SCIENCE GMBH,
`Patent Owner.
`____________
`U.S. Patent No. 10,533,183
`Issued: January 14, 2020
`____________
`DECLARATION OF NARENDRA YADAV, Ph.D.,
`IN SUPPORT OF PETITION FOR POST-GRANT REVIEW
`OF U.S. PATENT NO. 10,533,183
`
`
`Mail Stop: Patent Board
`Patent Trial and Appeal Board
`United States Patent and Trademark Office
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`
`
`CSIRO Exhibit 1002
`
`

`

`Declaration of Narendra Yadav, Ph.D.,
`in Support of Petition for Post-Grant Review
`of U.S. Patent No. 10,533,183
`
`
`TABLE OF CONTENTS
`Introduction ........................................................................................................ 1
`I.
`II. Qualifications ..................................................................................................... 1
`III. Materials Considered ......................................................................................... 3
`IV. Legal Standards .................................................................................................. 4
`A. Written description .................................................................................... 4
`B. Enablement ................................................................................................ 4
`C. Entitlement of priority ............................................................................... 5
`D. Anticipation ............................................................................................... 5
`E. Claim Construction .................................................................................... 5
`F. Person of Ordinary Skill in the Art ........................................................... 6
`V. Summary of my opinions ................................................................................... 6
`VI. Technology Background .................................................................................. 10
`A. Fatty acid nomenclature .......................................................................... 10
`B. Fatty acid biosynthesis ............................................................................ 13
`1. The aerobic biosynthetic pathway ................................................... 14
`2. Transformation of plants with binary vectors ................................. 16
`C. Triacylglycerides and the fatty acid composition of plants .................... 16
`1.
`Positional distribution of fatty acids in different lipid species ....... 19
`VII. Summary of the ‘183 Patent ............................................................................ 21
`A. The description of the ‘183 Patent and its priority applications ............. 21
`1. The description of the ‘183 Patent .................................................. 21
`2. The description of the parent and priority applications .................. 26
`B. The description of the ‘183 Patent compared to the description of Cirpus
`et al., PCT International Application Publication No. WO 2005/083093
`A2, published September 9, 2005 ........................................................... 28
`1. Binary vectors used for transformation of plant cells ..................... 31
`
`ii
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`CSIRO Exhibit 1002
`
`

`

`Declaration of Narendra Yadav, Ph.D.,
`in Support of Petition for Post-Grant Review
`of U.S. Patent No. 10,533,183
`
`2. The ‘093 publication discloses the sequence of the codon-optimized
`Δ5 elongase used in examples 4-13 of the ‘183 Patent................... 33
`3. Lipids produced by transformed plants ........................................... 35
`VIII. Detailed opinions ............................................................................................. 36
`A. Claim Construction .................................................................................. 36
`B. Lack of entitlement to priority and unpatentability of the claims ........... 39
`1. Lack of entitlement to priority ........................................................ 39
`2. Unpatentability of the claims .......................................................... 39
`C. Lack of written description of the claims ................................................ 40
`1. Lack of Written Description for oils, lipids and/or fatty acids
`produced by a transgenic Brassica plant wherein said oils, lipids
`and/or fatty acids comprise in the sn-2 position 25% to 40% by
`weight of eicosapentaenoic (EPA) based on the total EPA” recited
`in claim 1 ......................................................................................... 40
`2. Lack of Written Description for oils, lipids and/or fatty acids
`produced by a transgenic Brassica plant “wherein said oils, lipids
`and/or fatty acids comprise in the sn-2 position 40% to 60% by
`weight of docosapentaenoic acid (DPA) based on the total DPA”
`recited in claim 2 ............................................................................. 42
`3. Lack of Written Description for oils, lipids and/or fatty acids
`produced by a transgenic Brassica plant “wherein said oils, lipids
`and/or fatty acids comprise in the sn-2 position 15% to 35% by
`weight of docosahexanoic acid (DHA) based on the total DHA”
`recited in claim 3 ............................................................................. 44
`4. Lack of Written Description for “at least 20% by weight of EPA, at
`least 2% by weight of docosapentaenoic acid (DPA), and at least
`4% by weight of docosahexaenoic acid (DHA) based on the total
`fatty acids in the transgenic [Brassica] plant in the form of
`triacylglycerides,” recited in 1-8, and 17-23 ................................... 46
`5. Lack of Written Description for “at least 20% long chain
`polyunsaturated fatty acids (LCPUFAs) based on the total fatty
`acids in the transgenic [Brassica] plant” recited in claim 5 ........... 52
`
`iii
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`CSIRO Exhibit 1002
`
`

`

`Declaration of Narendra Yadav, Ph.D.,
`in Support of Petition for Post-Grant Review
`of U.S. Patent No. 10,533,183
`
`
`6. Lack of Written Description for “at least about 25% by weight of
`EPA in the form of triacylglycerides based on the total fatty acids
`in the transgenic [Brassica] plant” recited in claim 6 ..................... 54
`7. Lack of Written Description for “about 30% by weight of EPA and
`DHA in the form of triacylglycerides based on the total fatty acids
`in the transgenic [Brassica] plant” recited in claim 7 ..................... 55
`8. Lack of Written Description for oils, lipids and/or fatty acids
`produced by a transgenic Brassica plant comprising “at least 54%
`by weight of polyunsaturated ω3-fatty acids” recited in claim 8 ... 56
`D. Lack of Enablement of the Claims .......................................................... 61
`1. Lack of Enablement of oils, lipids and/or fatty acids produced by a
`transgenic Brassica plant “wherein said oils, lipids and/or fatty
`acids comprise in the sn-2 position 25% to 40% by weight of
`eicosapentaenoic (EPA) based on the total EPA” recited in claim 1
` ......................................................................................................... 61
`2. Lack of Enablement of oils, lipids and/or fatty acids produced by a
`transgenic Brassica plant “wherein said oils, lipids and/or fatty
`acids comprise in the sn-2 position 25% to 40% by weight of
`eicosapentaenoic (EPA) based on the total EPA” recited in claim 1
` ......................................................................................................... 62
`3. Lack of Enablement of oils, lipids and/or fatty acids produced by a
`transgenic Brassica plant “wherein said oils, lipids and/or fatty
`acids comprise in the sn-2 position 25% to 40% by weight of
`eicosapentaenoic (EPA) based on the total EPA” recited in claim 1
` ......................................................................................................... 63
`4. Lack of Enablement of oils, lipids and/or fatty acids produced by a
`transgenic Brassica plant comprising “at least 20% by weight of
`EPA”, “at least 2% by weight of DPA”, or “at least 4% by weight
`of DHA”, “based on the total fatty acids in the transgenic
`[Brassica] plant in the form of triacylglycerides” recited in claim 4
` ......................................................................................................... 64
`5. Lack of Enablement of oils, lipids and/or fatty acids produced by a
`transgenic Brassica plant comprising “at least 20% long chain
`
`iv
`
`CSIRO Exhibit 1002
`
`

`

`Declaration of Narendra Yadav, Ph.D.,
`in Support of Petition for Post-Grant Review
`of U.S. Patent No. 10,533,183
`
`
`polyunsaturated fatty acids (LCPUFAs) based on the total fatty
`acids in the transgenic [Brassica] plant”, recited in claim 5 .......... 67
`6. Lack of Enablement of oils, lipids and/or fatty acids produced by a
`transgenic Brassica plant comprising “at least about 25% by weight
`of EPA in the form of triacylglycerides based on the total fatty
`acids in the transgenic [Brassica] plant”, recited in claim 6 .......... 70
`7. Lack of Enablement of oils, lipids and/or fatty acids produced by a
`transgenic Brassica plant comprising “at about 30% by weight of
`EPA and DHA in the form of triacylglycerides based on the total
`fatty acids in the transgenic [Brassica] plant”, recited in claim 7 .. 71
`8. Lack of Enablement of oils, lipids and/or fatty acids produced by a
`transgenic Brassica plant comprising “at least 54% by weight of
`polyunsaturated ω3-fatty acids”, recited in claim 8 ........................ 72
`E. Anticipation of the claims ....................................................................... 74
`1. Claims 1-3 and 5-9 are Anticipated by Wu et al. (2005) Nat.
`Biotech. 1013-1017 ......................................................................... 74
`2. Claims 1-9 are Anticipated by, or obvious over, WO 2005/083093
`(BASF Plant Science GmbH).......................................................... 81
`3. Claims 1-9 are obvious over Wu et al. in view of the ‘093
`publication ....................................................................................... 82
`IX. Supplementation .............................................................................................. 83
`X. Conclusion ....................................................................................................... 84
`
`
`
`v
`
`CSIRO Exhibit 1002
`
`

`

`Declaration of Narendra Yadav, Ph.D.,
`in Support of Petition for Post-Grant Review
`of U.S. Patent No. 10,533,183
`
`
`I, Narendra Yadav, Ph.D., hereby declare as follows:
`
`I.
`
`INTRODUCTION
`1.
`I have been retained as an expert witness on behalf of Commonwealth
`
`Scientific and Industrial Research Organisation (“CSIRO”) for the above-captioned
`
`Petition for Post-Grant Review (“PGR”) of U.S. Patent No. 10,533,183 (“the ‘183
`
`Patent”). I am being compensated for my time in connection with this PGR at a
`
`consulting rate of $290 (USD) per hour. My compensation is in no way dependent
`
`on the outcome of this matter.
`
`II. QUALIFICATIONS
`Attached to this Declaration as “Appendix A” is my curriculum vitae,
`2.
`
`which provides a more detailed description of my education, training and experience
`
`in the relevant technology. Presently, I am the Director of Synthetic Biology at
`
`Napigen, where I study the science of molecular biology. I am also presently an
`
`independent biotechnology consultant in industrial and agricultural biotechnology,
`
`including genetic engineering of plants and microbes, biofuels, edible oils, and fish
`
`oil. I was also a founding member of the Science, Technology & Research Institute
`
`of Delaware.
`
`3.
`
`I served as a senior visiting scientist during a three-month appointment
`
`between November 2017 and January 2018 with Henry Daniell of the University of
`
`1
`
`CSIRO Exhibit 1002
`
`

`

`Declaration of Narendra Yadav, Ph.D.,
`in Support of Petition for Post-Grant Review
`of U.S. Patent No. 10,533,183
`
`Pennsylvania School of Dental Medicine (Philadelphia, Pennsylvania USA). In this
`
`capacity, I assisted towards establishing at the Pennovation Center; an agricultural
`
`biotechnology startup company relating to protein production in plants. I also held a
`
`five-month consultancy between December 2016 and April 2017 with Zymergen,
`
`Inc. (Emeryville, California USA) related to genome engineering.
`
`4.
`
`From 1981 to 2016, I was employed with E. I. du Pont de Nemours and
`
`Company (“DuPont”). In these 35 years, I held six positions of increasing
`
`responsibility in different businesses. While at DuPont between 2002-2012, I played
`
`a key role in a project involving the complex metabolic engineering of yeast (59
`
`transgenes) to create perhaps the richest natural source of ω-3 fatty acid, that
`
`included the discovery and overexpression of various enzymes known as
`
`desaturases, elongases and acyltransferases.
`
`5. While at DuPont between 1986-1994, I also initiated a new area of
`
`research and development on the genetic modification of lipids in oil crops. I was
`
`among the first scientists to clone genes encoding membrane bound desaturases
`
`(Δ-12/ω-6 desaturases and Δ-15/ω-3 desaturases) from plants, and I subsequently
`
`cloned genes encoding these desaturases from microbes. While my work centered
`
`on Δ-15/ω-3 desaturases, I also became familiar during this time period with other
`
`fatty acid desaturases and elongases for making polyunsaturated fatty acids.
`
`2
`
`CSIRO Exhibit 1002
`
`

`

`Declaration of Narendra Yadav, Ph.D.,
`in Support of Petition for Post-Grant Review
`of U.S. Patent No. 10,533,183
`
`I hold a Doctor of Philosophy degree (“Ph.D.”) in Botany/Biochemistry
`
`6.
`
`from Michigan State University (East Lansing, Michigan USA). I also earned a
`
`Master of Philosophy in Life Sciences from Jawaharlal Nehru University (New
`
`Delhi, India), and a Master of Science in Botany from The University of Delhi (Delhi
`
`India). I obtained my Bachelor of Science in Botany also from Delhi University.
`
`7.
`
`I have published extensively in the field of plant science, including on
`
`the topic of uses of desaturases and elongases. I am the named inventor on at least
`
`65 granted patents as well as on a few pending patent applications, including one
`
`filed in August 2018. I have authored over 24 peer-reviewed papers. I received the
`
`Invention-Of-The-Year Award in 2008 by DuPont (Pioneer Seed Company) for high
`
`oleate soybean, the DuPont Accomplishment Award for novel fatty acid desaturases
`
`in 2012, and the DuPont Accomplishment Award in 2013 for generating a yeast
`
`strain producing eicosapentaenoic acid at 30% dry cell weight.
`
`III. MATERIALS CONSIDERED
`8.
`I provide opinions in this declaration based on my education, training,
`
`background, and experience, as well as the documents I have reviewed to date,
`
`including the ‘183 Patent. Those documents, and the other materials cited in this
`
`declaration, are listed in Appendix B. I have either read the materials listed in
`
`Appendix B or reviewed summarized data provided by counsel to CSIRO.
`
`3
`
`CSIRO Exhibit 1002
`
`

`

`Declaration of Narendra Yadav, Ph.D.,
`in Support of Petition for Post-Grant Review
`of U.S. Patent No. 10,533,183
`
`
`IV. LEGAL STANDARDS
`9.
`In preparing this declaration, certain patent law concepts have been
`
`explained to me by CSIRO’s counsel, including the legal standard for interpreting
`
`claims, as well as those for assessing written description, enablement, anticipation,
`
`and obviousness.
`
`A. Written description
`10.
`I have been informed by counsel that a claim in a granted patent must
`
`be sufficiently supported by the disclosure in the patent’s specification, read in the
`
`context of what a person of ordinary skill in the art would have known at the time of
`
`the claimed invention. I understand that the basic inquiry for written description is
`
`whether the specification provides sufficient information for the person or ordinary
`
`skill to recognize that the named inventors possessed the full scope of the claimed
`
`invention.
`
`B.
`11.
`
`Enablement
`I have been informed by counsel that, in addition to written description,
`
`a patent specification must also enable a person of ordinary skill in the art to make
`
`and use the full scope of the claimed invention without undue experimentation as of
`
`its effective filing date. I understand that multiple factors should be considered when
`
`making this determination. These factors include (1) the quantity of experimentation
`
`necessary, (2) the amount of direction or guidance presented, (3) the presence or
`
`4
`
`CSIRO Exhibit 1002
`
`

`

`Declaration of Narendra Yadav, Ph.D.,
`in Support of Petition for Post-Grant Review
`of U.S. Patent No. 10,533,183
`
`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..
`
`C. Entitlement of priority
`12.
`I have been informed by counsel that, for the claims of an application
`
`to be entitled to an earlier application’s filing date, the earlier application must
`
`provide written description and enablement of the claims, as of the earlier
`
`application’s filing date.
`
`D. Anticipation
`13.
`I have been informed by counsel that a claim is anticipated when a
`
`single prior art reference discloses, either expressly or inherently, each and every
`
`claim element arranged in the order specified by the claim. I also understand that
`
`whether a document qualifies as prior art against a claim depends on the effective
`
`filing date to which the claim is entitled.
`
`E. Claim Construction
`14.
`I have been informed by counsel that the Patent Trial and Appeal Board
`
`(“PTAB”) applies the same claim construction standard used in district courts, where
`
`the claims are given their ordinary meaning as understood by one skilled in the art
`
`at the time of the invention, informed by the claim language itself, the specification,
`
`and the prosecution history. I also understand that “extrinsic evidence”—i.e.,
`
`5
`
`CSIRO Exhibit 1002
`
`

`

`Declaration of Narendra Yadav, Ph.D.,
`in Support of Petition for Post-Grant Review
`of U.S. Patent No. 10,533,183
`
`evidence other than the patent and prosecution history—can be relevant in
`
`determining how a skilled artisan would understand terms of art used in the claims.
`
`I have been informed, however, that extrinsic evidence may not be used to contradict
`
`the meaning of the claims as described in the intrinsic evidence—i.e., evidence in
`
`the claim language itself, the specification, and the prosecution history.
`
`F.
`15.
`
`Person of Ordinary Skill in the Art
`In my opinion, a person of ordinary skill in the art (a “POSITA”) as of
`
`the date of invention would have been at least a Ph.D. in molecular biology,
`
`molecular genetics, biochemistry, or a related field and at least 3-5 years of
`
`experience in molecular genetics or biology, plant genetics, or recombinant DNA
`
`techniques. An individual need not have every qualification enumerated above and
`
`more experience, such as research work on plant lipids, can compensate for less
`
`formal education.
`
`V.
`
`SUMMARY OF MY OPINIONS
`16.
`I understand that the ‘183 Patent issued from U.S. Application No.
`
`16/371,837 (“the ‘837 application), which was filed on April 1, 2019 as a
`
`continuation of ‘U.S. Application No. 15/256,914 (the ‘914 application) which was
`
`filed on September 6, 2016 and issued as U.S. Patent No. 10,301,638 on May 28,
`
`2019 (“the ‘683 Patent”, Ex. 1007). U.S. Application No. 15/256,914 was filed as a
`
`6
`
`CSIRO Exhibit 1002
`
`

`

`Declaration of Narendra Yadav, Ph.D.,
`in Support of Petition for Post-Grant Review
`of U.S. Patent No. 10,533,183
`
`continuation of U.S. Application No. 12/280,090 which was a §371 national stage
`
`entry of PCT International Application No. PCT/EP2007/051675, filed February 21,
`
`2007 (Ex. 1003), and claimed priority to German Patent Application No. DE 10 2006
`
`008 030.0, filed February 21, 2006 (Ex. 1004), and European Patent Application No.
`
`06120309.7, filed September 7, 2006 (Ex. 1005). Collectively, all the applications
`
`to which the ‘183 Patent claims priority (i.e. U.S. Application No. 12/280,090,
`
`PCT/EP2007/051675, DE 10 2006 008 030.0, and 06120309.7) are referred to herein
`
`as “priority applications.”
`
`17.
`
`I understand that the specification of the ‘183 Patent does not differ
`
`from that of its parent application, U.S. Application No. 15/256,914, or its
`
`grandparent application, U.S. Application No. 12/280,090 which was the national
`
`stage entry of and shares the same description with PCT/EP2007/051675. Further,
`
`the two applications to which PCT/EP2007/051675 claims priority, i.e. German
`
`Patent Application No. DE 10 2006 008 030.0 and European Patent Application
`
`No. 06120309.7, do not contain any description that is not in the specification of
`
`PCT/EP2007/051675. Accordingly, any statement made herein regarding a lack of
`
`description in the ‘183 Patent applies equally to the description of the priority
`
`applications.
`
`7
`
`CSIRO Exhibit 1002
`
`

`

`Declaration of Narendra Yadav, Ph.D.,
`in Support of Petition for Post-Grant Review
`of U.S. Patent No. 10,533,183
`
`18. The ‘183 Patent, which I understand has been assigned to BASF Plant
`
`Science Gmbh (“BASF”), claims oils, lipid and/or fatty acids produced by a
`
`transgenic Brassica plant. Claim 1 requires that said oils, lipids and/or fatty acids
`
`comprise in the sn-2 position 25% to 40% by weight eicosapentaenoic [acid] (EPA)
`
`based on the total EPA. Claim 2 depends from claim 1 and further specifies that said
`
`oils, lipids and/or fatty acids comprise in the sn-2 position 40% to 60% by weight of
`
`docosapentaenoic acid (DPA) based on the total DPA. Claim 3 also depends from
`
`claim 1 and further specifies that said oils, lipids and/or fatty acids comprise in the
`
`sn-2 position 15% to 35% by weight of docosahexanoic acid (DHA) based on the
`
`total DHA. Claims 4-9 also depend from claim 1 and specify amounts of various
`
`fatty acids either based on the total fatty acids in the transgenic plant or based on the
`
`total fatty acids in the transgenic plant in the form of triacylglycerides. I understand
`
`that claim 1 is the only independent claim of the ‘183 Patent and that all other claims
`
`require at least the feature recited in claim 1.
`
`19.
`
`I have been asked to consider whether the description in U.S. Patent
`
`No. 10,533,183 (“the ‘183 Patent”) demonstrates that the inventors had possession
`
`of the full scope of the invention defined in claims 1-9.
`
`20.
`
`In my opinion, elaborated below, none of claims 1-9 is adequately
`
`described or supported by the ‘183 Patent. There is no description in the ‘183 Patent
`
`8
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`CSIRO Exhibit 1002
`
`

`

`Declaration of Narendra Yadav, Ph.D.,
`in Support of Petition for Post-Grant Review
`of U.S. Patent No. 10,533,183
`
`of the positional distribution of EPA, DPA, or DHA in oils, lipids and/or fatty acids
`
`from a transgenic Brassica plant. Further, there is no experimental data or example
`
`in the ‘183 Patent of oils, lipids and/or fatty acids produced by a transgenic Brassica
`
`plant with the features recited in the claims. The information contained in the ‘183
`
`Patent does not in my opinion convey that the inventors had possession of any, let
`
`alone all, of the subject matter claimed.
`
`21.
`
`I have also been asked to consider whether the POSITA, reading the
`
`specification of the ‘183 Patent, could make and use the full scope of the invention
`
`defined in claims 1-9 without undue experimentation, either as of February 21,
`
`2006,as of the September 6, 2016 filing date of the parent ‘914 application, or even
`
`as of the April 1, 2020 filing date of the ‘837 application.
`
`22.
`
`In my opinion, as elaborated below, the specification does not teach the
`
`POSITA how to make and use the invention recited in any of claims 1-9 without
`
`undue experimentation as of February 21, 2006. Even as of September 6, 2016 or
`
`April 1, 2019, the description in the ‘183 Patent is insufficient to teach a POSITA
`
`how to make and use the full scope of the invention defined in claims 1-9.
`
`23.
`
`I have also been asked to consider whether literature in the art disclosed
`
`the invention recited in claims 1-9, as of February 21, 2006, as of September 6, 2016,
`
`or as of April 1, 2019.
`
`9
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`CSIRO Exhibit 1002
`
`

`

`Declaration of Narendra Yadav, Ph.D.,
`in Support of Petition for Post-Grant Review
`of U.S. Patent No. 10,533,183
`
`I have been informed by counsel that, based on my analysis of written
`
`24.
`
`description and enablement, the ‘183 Patent is not entitled to its asserted priority
`
`date in 2006, and therefore would not have an effective filing date prior to April 1,
`
`2019. Nevertheless, after considering the art discussed in this declaration, I find that
`
`examples of oils, lipids and fatty acids according to the claims were described by art
`
`dated prior to February 21, 2006.
`
`VI. TECHNOLOGY BACKGROUND
`25. Generally, fatty acids are biomolecules (important component of lipids
`
`or oils) consisting of a chain of carbon atoms with a carboxyl group (COOH) on one
`
`end and a methyl group (CH3) on the other end. The carbons in the middle of the
`
`chain are each bonded to one or more hydrogen atoms. Fatty acids may be “saturated
`
`fatty acids” (in which there are no double bonds between carbons in the chain);
`
`“unsaturated fatty acids” (in which there is at least one double bond between carbons
`
`in the chain); or “polyunsaturated fatty acids” (“PUFAs”) (in which there are at least
`
`two such double bonds).
`
`A.
`Fatty acid nomenclature
`26. Fatty acids can be represented using the nomenclature “C:D” where
`
`“C” is the number of carbon atoms in the fatty acid and “D” is the number of double
`
`bonds in the fatty acid. Thus, fatty acids with a “D” of 2 or greater are
`
`10
`
`CSIRO Exhibit 1002
`
`

`

`Declaration of Narendra Yadav, Ph.D.,
`in Support of Petition for Post-Grant Review
`of U.S. Patent No. 10,533,183
`
`“polyunsaturated fatty acids”. This notation, however, is not a complete
`
`representation because different fatty acids can have the same C:D numbers.
`
`Accordingly, this notation is usually paired with either a Δx or ω−x term as discussed
`
`below.
`
`27. As an example, the chemical structure of one fatty acid, stearidonic
`
`acid, is provided below:
`
`28. The carbon next to the carboxyl group (COOH) on the left is labeled as
`
`carbon “α” (alpha) and the last carbon, at the methyl group (CH3) is labelled as ω
`
`
`
`(omega).
`
`29. The position of the carbon atoms in the backbone of a fatty acid can be
`
`also indicated by numbering them, either from the carboxyl end or from the methyl
`
`end of the carbon chain. Counted from the carboxyl end, it is represented by the Δx,
`
`or equivalently, by the C-x notation, with x=1, 2, 3, etc. (numbers under the carbon
`
`chain in the diagram, where “C-1” or “Δ1” is the carbon in the carboxyl group). If
`
`the position is counted from the methyl end, then it is represented by the ω-x
`
`notation, or equivalently, by the n-x notation (numbers above the carbon chain in the
`
`diagram, where ω-1 or n-1 refers to the methyl carbon).
`
`11
`
`CSIRO Exhibit 1002
`
`

`

`Declaration of Narendra Yadav, Ph.D.,
`in Support of Petition for Post-Grant Review
`of U.S. Patent No. 10,533,183
`
`30. Accordingly, when Δ notation is used, the 18-carbon fatty acid shown
`
`in the diagram is named “18:4 Δ6,9,12,15”. When “ω-x” notation is used, only the
`
`position of the double bond which is closest to the methyl end is indicated, even if
`
`multiple double bonds exist and the 18-carbon fatty acid shown in the diagram is
`
`named “18:4ω-3” or “18:4n-3”. Accordingly, any PUFA that has its first double
`
`bond on the third carbon from the methyl end of the carbon chain is designated as
`
`omega-3 (ω-3), whereas a PUFA with its first double bond on the sixth carbon from
`
`end of the carbon chain is designated as omega-6 (ω-6).
`
`31. A summary of omega-3 (ω-3) and omega-6 (ω-6) polyunsaturated fatty
`
`acids is provided below:
`
`Omega-6 (ω6) Fatty Acids
`Name
`
`Linoleic acid (LA)
`
`γ-Linolenic acid (GLA)
`
`Δ notation
`
`18:2Δ9,12
`
`18:3Δ6,9,12
`
`Dihomo-γ-linolenic acid (DGLA)
`
`20:3Δ8,11,14
`
`Arachidonic acid (ARA)
`
`Adrenic acid
`
`Tetracosatetraenoic acid
`
`20:4Δ5,8,11,14
`
`22:4Δ7,10,13,16
`
`24:4Δ9,12,15,18
`
`Tetracosapentaenoic acid
`
`24:5Δ6,9,12,15,18
`
`Docosapentaenoic acid (ω-6 DPA) 22:5Δ4,7,10,13,16
`
`ω notation
`
`18:2ω-6
`
`18:3ω-6
`
`20:3ω-6
`
`20:4ω-6
`
`22:4ω-6
`
`24:4ω-6
`
`24:5ω-6
`
`22:5ω-6
`
`12
`
`CSIRO Exhibit 1002
`
`

`

`Declaration of Narendra Yadav, Ph.D.,
`in Support of Petition for Post-Grant Review
`of U.S. Patent No. 10,533,183
`
`
`Omega-3 (ω3) Fatty Acids
`Name
`
`Hexadecatrienoic acid (HTA)
`
`α-Linolenic acid (ALA)
`
`Stearidonic acid (SDA)
`
`Eicosatetraenoic acid (ETA)
`
`Δ notation
`
`16:3Δ7,10,13
`
`18:3Δ9,12,15
`
`18:4Δ6,9,12,15
`
`20:4Δ8,11,14,17
`
`ω notation
`
`16:3ω-3
`
`18:3ω-3
`
`18:4ω-3
`
`20:4ω-3
`
`Eicosapentaenoic acid (EPA)
`
`20:5Δ5,8,11,14,17
`
`20:5ω-3
`
`Docosapentaenoic acid (DPA)
`
`22:5Δ7,10,13,16,19
`
`22:5ω-3
`
`Docosahexaenoic acid (DHA)
`
`22:6Δ4,7,10,13,16,19 22:6ω-3
`
`Tetracosapentaenoic acid
`
`24:5Δ9,12,15,18,21
`
`24:5ω-3
`
`Tetracosahexaenoic acid
`
`24:6Δ6,9,12,15,18,21 24:6ω-3
`
`B.
`Fatty acid biosynthesis
`32. Although there are multiple pathways for the biosynthesis of PUFAs
`
`
`
`
`
`and LC-PUFAs1, the ‘183 Patent focuses on the biosynthesis of PUFAs and LC-
`
`
`1 Long-chain polyunsaturated
`
`fatty acids
`
`(“LC-PUFAs”) may
`
`refer
`
`to
`
`polyunsaturated fatty acids with 18 or more carbons, or 20 or more carbons. The
`
`‘183 Patent does not provide a precise definition for LC-PUFA, although for the
`
`purposes of this Declaration it is not necessary for there to be a precise definition of
`
`
`
`13
`
`CSIRO Exhibit 1002
`
`

`

`Declaration of Narendra Yadav, Ph.D.,
`in Support of Petition for Post-Grant Review
`of U.S. Patent No. 10,533,183
`
`PUFAs in transgenic plants that have been transformed with binary vectors
`
`comprising enzymes with activity in the aerobic biosynthetic pathway, an overview
`
`of which is provided below.
`
`1.
`The aerobic biosynthetic pathway
`In the aerobic biosynthetic pathway, PUFAs and LC-PUFAs are
`
`33.
`
`synthesized through alternating steps of “desaturation” (the addition of a double
`
`bond/removal of hydrogen atoms) and “elongation” (the addition of two carbon
`
`atoms) by desaturase and elongase enzymes, respectively.
`
`34. Desaturases are enzymes that are often referred to as “Δx”-desaturase,
`
`where “x” refers to the carbon atom at which the new double bond is created.
`
`Desaturases may also be referred to as ω3 or ω6 desaturases, which add a double
`
`bond between the methyl end of the fatty acid chain and a pre-existing double bond.
`
`35. Elongases are enzymes that lengthen the fatty acid chain by insertion
`
`of a two-carbon unit. Like desaturases, elongases are often referred to as “Δx”-
`
`elongase. In contrast to desaturases, the “x” does not refer to where the elongase
`
`
`LC-PUFA because the claims reciting LC-PUFA (i.e. claims 5 and 14) specify “C20
`
`and/or C22 fatty acid molecules having at least four double bonds”
`
`14
`
`CSIRO Exhibit 1002
`
`

`

`Declaration of Narendra Yadav, Ph.D.,
`in Support of Petition for Post-Grant Review
`of U.S. Patent No. 10,533,183
`
`adds the new two-carbon group2, but rather to where the first double bond in the fatty
`
`acid must be in order for the elongase to be able to act on the substrate.
`
`36. FIG. 1 of PCT International Application Publication No. WO
`
`2005/083093 A2, published September 9, 2005, by Patent Owner, summarizes
`
`possible pathways of ω-3 and ω-6 LC-PUFA synthesis.
`
`
`
`
`2 Elongases add the two-carbon unit at the carboxyl end of the fatty acid chain.
`
`15
`
`CSIRO Exhibit 1002
`
`

`

`Declaration of Narendra Yadav, Ph.D.,
`in Support of Petition for Post-Grant Review
`of U.S. Patent No. 10,533,183
`
`
`2.
`Transformation of plants with binary vectors
`“Transformation” is the process of inserting an exogenous or
`
`37.
`
`recombinant gene into an organism, generally by placing the gene of interest into a
`
`circular length of DNA, commonly called a “plasmid construct” or “construct”3,
`
`along with other genetic elements, such as an appropriate promoter. The construct
`
`can then be inserted into the chromosomes of plants by Agrobacterium-mediated
`
`transformation. The insertion of such new exogenous or recombinant genes into the
`
`plant chromosomes results in a transgeni