1 2 3 6 7 ILLUMINA INC., et al., Case No. 20-cv-01465-WHO
8 Plaintiffs, CLAIM CONSTRUCTION v. 9
10 BGI GENOMICS CO., LTD., et al., Defendants. 11
12 14 In this matter, plaintiffs Illumina Inc. and Illumina Cambridge Ltd. (collectively, 15 “Illumina”) assert infringement claims against defendants BGI Genomics Co., Ltd., BGI Americas 16 Corp., MGI Tech Co., Ltd., MGI Americas, Inc., and Complete Genomics Inc. (collectively 17 “BGI”). The parties request construction of five terms from three patents asserted by Illumina, all 18 of which relate to sequencing of nucleic acids. My constructions are below. 21 BGI and Illumina are competitors in the field of genomic sequencing. This matter, 22 (“Illumina II”) is related to Illumina Inc., et al., v. BGI Genomics Co., Ltd., et al., Case No. 19-cv- 23 3770 (N.D. Cal.) (“Illumina I”). Illumina filed the complaint in Illumina I on June 27, 2019. 24 Illumina I,1 Dkt. No. 1. In that matter Illumina alleges that BGI infringes U.S. patent number 25 9,410,200 (the “’200 patent”) and U.S. patent number 7,566,537 (the “’537 patent”) by selling its 26 sequencers and related reagents (collectively, “standardMPS”). Id. ¶¶ 2, 33-44. 27 1 Illumina filed the complaint in the present case, Illumina II on February 27, 2020, after it 2 learned of a new product developed by BGI called CoolMPS™ (“CoolMPS”). Dkt. No. 1. In this 3 lawsuit, Illumina asserts infringement of U.S. Patent numbers 7,771,973 (the “’973 patent”), 4 7,541,444 (the “’444 patent”), and 10,480,025 (the “’025 patent”). Id. ¶ 2. The ’973, ’444, and 5 ’537 patents claim priority to or are a divisional of the same patent application. Id. ¶ 38. Illumina 6 claims BGI’s CoolMPS products, which are purportedly based upon new sequencing chemistry, 7 infringe claim 13 of the ’973 patent, claim 3 of the ’444 patent, and claim 1 of the ’025 patent. Id. 8 ¶¶ 48, 65, 146, 232. 10 Illumina is a market leader in the field of sequencing deoxyribonucleic acid (“DNA”), and 11 specifically in a method known as sequencing-by-synthesis (“SBS”). Illumina I, Dkt. No. 1 12 (“Compl.”) ¶¶ 1, 36. DNA is comprised of molecules called nucleotides, which consist of a sugar 13 molecule and a phosphate molecule that form the backbone of each DNA strand, and a chemical base, 14 which binds with a complementary chemical base in the other strand. Dkt. No. 184 at 3. The chemical 15 base may be one of four molecules: adenine, guanine, cytosine, and thymine. Id. at 2-3. Each one of 16 these molecules binds or pairs with only one other molecule; for example, guanine only pairs with 17 cytosine and adenine only pairs with thymine. Id. at 3. 18 SBS uses this basic complementary pairing principle in order to sequence unknown DNA 19 molecules. Id. at 3. It is possible to determine the sequence of one strand of a DNA molecule to be 20 sequenced, often called target DNA, by identifying the sequence of the complementary nucleotides 21 that bind with it. Id. In SBS, nucleotides are “incorporated” or bound to the target DNA strand and 22 “read” one by one. Id. at 6. In other words, nucleotides are added one at a time to bind with a 23 complementary nucleotide base in the target DNA strand, and each time a nucleotide is added it is 24 identified as adenine, guanine, cytosine, or thymine. Id. at 3-6. In this way, it is possible to determine 25 the sequence of the target DNA strand. 26 Illumina’s patents specify several aspects of SBS, and in particular the method of adding 27 nucleotides one at a time so that each one can be read before another nucleotide is added. Id. at 6-7. 1 Illumina’s patented technology and the subject of some of the claims at issue. Id. 2 A. 7444 Patent 3 The °444 patent shares a specification with the ’973 patent and is titled “Modified 4 || Nucleotides.” See Dkt. No. 1-2 (“444 patent”). Claim 1 of the ’444 patent provides for “[a] modified 5 nucleotide molecule comprising a purine or pyrimidine base and a ribose or deoxyribose sugar moiety 6 || having a removable 3’-OH blocking group covalently attached thereto, such that the 3’ carbon atom has 7 attached a group of the structure —O—Z wherein Z 1s any of” five enumerated structures. Dkt. No. 1- 8 2 (444 patent’) 85:65-86:36. It further states: 9 10 Oe ul wherein # is any of —C(R” ),—O-—R", —C(R"), NIR") >. —C{R),—N(H)R", —C(R’"), S—R" and —C(R’) 12 Ns . wherein] —C(R’"),——R" is of the formula —CR* Sa - & 13 (R°)—0O—CR*(R*}—OR® or of the formula —CR* (R°}—-O-—CRR*}—SR®; and wherein —C(R'), 14 S—R" is of the formula —CR*(R*}-S—CR(R*) © OR? of of the formula —CR“(R7}—S—CR“(R7}—SR®, 2 15 wherein each R" is or is part of a removable protecting A 16 group; each BY is independently a hydrogen atom, an alkyl, sub- 3 17 stituted alkyl, arvlalkyl, alkenyl, alkynwl., arvl. het- endarvl, heteroevelic, acyl, cyano, alkoxy, arvloxy, hel- 7 18 eroaryloxy or amido group, or a detectable label attached through a linking group: or (R"), represents an 19 alkylidene group of fomiula —C(R™), wherein each R™ may be the same or different and is selected from the 20 group composing hydrogen and halogen atoms and alkyl groups: 21 each R? and B¢ is independently a hydrogen atom or an 0 alkwl group; Risalkyl. cycloalkyl alkenyl, cycloalkenyl or benzyl: and 23 wherein said molecule may be reacted to yield an interme- cate in which each RY is exchanged for A, which inter- 24 mediate dissociates under aqueous conditions to afford a molecule with a free FOE: with the prowiso that where 25 7 is —C(R"),—S—R", both R’” groups are not H 26 Id. at 86:4-35. Claim 3 states, in its entirety, “[a] molecule according to claim 1 wherein Z is an y 27 azidomethyl group.” Id. 86:39-40. 28
B. °973 Patent The °973 patent is a continuation of the °444 patent and shares a specification with the 2 °444 patent. See Dkt. No. 1-1 (“’973 patent”). Claim | of the ’973 patent claims “A method for 3 determining the sequence of a target single-stranded polynucleotide, comprising monitoring the 4 sequential incorporation of complementary nucleotides wherein at least one incorporation is of a 5 nucleotide having a removable 3’ — OH blocking group covalently attached thereto, such that the 3’ 6 carbon atom has attached a group of the structure -O—Z.” Id. at 86:24-32. It further states: 4 8 9 wherein 7 is any of allyl, —C(R"),—N,. —C(R’"),—O R", —C(R'),—N(R"),. C(R"),—N(H)R", or 10 —C(R™),—S—R", wherein c(R”), O—R" is of the formula — CRIR*) ll O—CR*(R°}—OR?* or of the formula —CR"(R*}—O—CR" (R°}—SR®; and wherein —C(R’"}, S—R" is of the formula 12 □□□□□□□□□□□□□□□□□□□□□ or of the formula —CR* (R°}—S—CRYR5)—SR*°: 13 each R" is or is part of a removable protecting group; each R'is independently a hydrogen atom, an alkyl, sub- 5 14 stituted alkyl, arylalkyl, alkenyl, alkynyl, aryl, het- eroaryl, heterocyclic, acyl, cyano, alkoxy, aryloxy, het- eroaryloxy or amido group, er a detectable label 15 attached through a linking group; or (R'), represents an alkylidene group of formula —C(R™"), wherein each R™ 16 may be the same or different and is selected from the group comprising hydrogen and halogen atoms and 17 alkyl groups; each R* and R* is independently a hydrogen atom or an Z 18 alkyl group; and R° is alkyl, cycloalkyl, alkenyl, cycloalkenyl or benzyl, 19 and wherein the blocking group is removed prior to introduc- tion of the next complementary nucleotide
Id. 86:32-56. Claim 13 of the 973 patent states in full “The method of claim 1 wherein Z is an azidomethyl group.” Jd. at 88:37-38. 22 C. ’025 Patent 23 34 The °025 patent shares a specification with the °537 and ’200 patents asserted in □□□□□□□□□ I,
95 and is titled “Labeled Nucleotides.” See Dkt. No. 1-3 (“025 patent”). Claim 1 of the ’025 patent 5 claims “A nucleotide or nucleoside molecule having a ribose or deoxyribose sugar moiety and a 6 37 base linked to a detectable label via a cleavable linker, wherein the sugar moiety comprises a
38 protecting group attached via a 3’ oxygen atom, and wherein said protecting group comprises an
1 azido group that can be modified or removed to expose a 3’ OH group.” Id. at 21:19-24. 3 Claim construction is a matter of law. See Markman v. Westview Instruments, Inc., 517 4 U.S. 370, 372 (1996); Vitronics Corp. v. Conceptronic, Inc., 90 F.3d 1576, 1582 (Fed. Cir. 1996). 5 “Generally, a claim term is given its ordinary and customary meaning—the meaning that a term 6 would have to a person of ordinary skill in the art in question at the time of the invention.” 7 Howmedica Osteonics Corp. v. Zimmer, Inc., 822 F.3d 1312, 1320 (Fed. Cir. 2016) (internal 8 quotation marks and citation omitted). In determining the proper construction of a claim, a court 9 begins with the intrinsic evidence of record, consisting of the claim language, the patent 10 specification, and, if in evidence, the prosecution history. Phillips v. AWH Corp., 415 F.3d 1303, 11 1313 (Fed. Cir. 2005); see also Vitronics, 90 F.3d at 1582. “A claim term used in multiple claims 12 should be construed consistently . . . .” Inverness Med. Switzerland GmbH v. Princeton 13 Biomeditech Corp., 309 F.3d 1365, 1371 (Fed. Cir. 2002). 14 “The appropriate starting point . . . is always with the language of the asserted claim itself.” 15 Comark Commc’ns, Inc. v. Harris Corp., 156 F.3d 1182, 1186 (Fed. Cir. 1998). “[T]he ordinary 16 and customary meaning of a claim term is the meaning that the term would have to a person of 17 ordinary skill in the art in question at the time of the invention, i.e., as of the effective filing date 18 of the patent application.” Phillips, 415 F.3d at 1312. “There are only two exceptions to this 19 general rule: 1) when a patentee sets out a definition and acts as his own lexicographer, or 2) when 20 the patentee disavows the full scope of a claim term either in the specification or during 21 prosecution.” Thorner v. Sony Computer Entm’t Am. LLC, 669 F.3d 1362, 1365 (Fed. Cir. 2012). 22 Such redefinition or disavowal need not be express to be clear. Trustees of Columbia Univ. in City 23 of New York v. Symantec Corp., 811 F.3d 1359, 1364 (Fed. Cir. 2016). 24 Like a person of ordinary skill in the art, courts read terms in the context of the claim and 25 of the entire patent, including the specification. Phillips, 415 F.3d at 1313. The specification is 26 “the single best guide to the meaning of a disputed term.” Vitronics, 90 F.3d at 1582. “The 27 construction that stays true to the claim language and most naturally aligns with the patent’s 1 Marposs Societa’ per Azioni, 158 F.3d 1243, 1250 (Fed. Cir. 1998). The court may also consider 2 the prosecution history of the patent, if in evidence. Markman, 52 F.3d at 980. The prosecution 3 history may “inform the meaning of the claim language by demonstrating how the inventor 4 understood the invention and whether the inventor limited the invention in the course of 5 prosecution, making the claim scope narrower than it would otherwise be.” Phillips, 415 F.3d at 6 1317 (citing Vitronics, 90 F.3d at 1582-83); see also Chimie v. PPG Indus., Inc., 402 F.3d 1371, 7 1384 (Fed. Cir. 2005) (“The purpose of consulting the prosecution history in construing a claim is 8 to exclude any interpretation that was disclaimed during prosecution.”) (internal quotations 9 omitted). 10 In most situations, analysis of this intrinsic evidence alone will resolve claim construction 11 disputes, Vitronics, 90 F.3d at 1583; however, a court can further consult “trustworthy extrinsic 12 evidence” to compare its construction to “widely held understandings in the pertinent technical 13 field,” Pitney Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1309 (Fed. Cir. 1999). 14 Extrinsic evidence “consists of all evidence external to the patent and prosecution history, 15 including expert and inventor testimony, dictionaries, and learned treatises.” Markman, 52 F.3d at 16 980. All extrinsic evidence should be evaluated in light of the intrinsic evidence, Phillips, 415 17 F.3d at 1319, and courts should not rely on extrinsic evidence in claim construction to contradict 18 the meaning of claims discernible from examination of the claims, the written description, and the 19 prosecution history, Pitney Bowes, 182 F.3d at 1308 (citing Vitronics, 90 F.3d at 1583). 21 A. “wherein the blocking group is removed prior to introduction of the next complementary nucleotide” 22 23 Patent/Term Illumina’s Proposal BGI’s Proposal 24 “wherein the blocking wherein the blocking group is wherein the blocking group group is removed prior removed before the next must be removed before 25 to introduction of the complementary nucleotide is putting or placing next complementary incorporated into a growing complementary nucleotides 26 nucleotide” nucleotide strand complementary into the mixture that contains to the target single-stranded the target and growing 27 ’973 Patent: claim 1, 13 polynucleotide being sequenced polynucleotide chains 1 The parties dispute the proper construction of the term “wherein the blocking group is 2 removed prior to introduction of the next complementary nucleotide.” The parties’ briefing 3 largely rehashes arguments raised during briefing on Illumina’s preliminary injunction motions 4 that I previously discussed in my order in Illumina I, granting Illumina’s motions. See Illumina I, 5 Dkt. No. 185 (“PI Order”) at 5-7. Consistent with my PI Order, I conclude that BGI’s proposed 6 construction in this case “would import a limitation into the patent claim that is not supported by 7 anything in the patent specification.” Id. at 6. In contrast, Illumina’s proposed construction 8 accurately captures how a person of ordinary skill in the art at the time of the invention would 9 have understood the disputed claim. 10 The parties’ dispute turns primarily on the meaning of the word “introduction” in claim 1 11 of the ’973 patent. Illumina argues that “introduction” is used largely interchangeably with the 12 word “incorporation” in the claim and that here it refers to a complementary nucleotide being 13 “incorporated into a growing nucleotide strand.” Dkt. No. 184 at 8. BGI, in contrast, argues that, 14 because the words “incorporation” and “introduction” are different, they are presumed to have 15 different meanings under patent law and that “introduction,” in this case, refers to adding 16 complementary nucleotides to a reaction mixture. Dkt. No. 191, BGI Responsive Claim 17 Construction Brief (“BGI Resp.”) at 15. 18 As explained in my PI Order, although different patent terms are presumed to have 19 different meanings, review of the patent claims and specification here reveal that, in claim 1 of the 20 ’973 patent, the term “introduction” of nucleotides is used “in a way very similar to, if not 21 interchangeably with the word ‘incorporation.’” PI Order at 6. Review of the claim language and 22 specification reveal that Illumina’s proposed construction, not BGI’s, reflects how a person of 23 ordinary skill in the art would understand the term. 24 “The focus of the patent is on the use of a blocking group to prevent new nucleotides from binding. There is no significance in the patent 25 in introducing new nucleotides before or after removal of the blocking group. The patent does not describe precisely when the blocking 26 group should be removed or that removal must occur before ‘introduction’ (in addition to before incorporation) of new 27 nucleotides. Instead, the claimed invention focuses on removal of the 1 PI Order at 5-6 (internal citation omitted). Given the focus of the patent, the term “introduction” 2 in claim 1 appears to refer to a complementary nucleotide being “incorporated into a growing 3 nucleotide strand,” not to nucleotides being added to a reaction mixture. See Phillips, 415 F.3d at 4 1316 (“The construction that stays true to the claim language and most naturally aligns with the 5 patent’s description of the invention will be, in the end, the correct construction.”) (citation 6 omitted). 7 BGI argues that the claimed method involves a separate discrete step of bringing 8 nucleotides in contact with the target strand by adding nucleotides to the reaction mixture, a 9 process described in the patent specification. Dkt. No. 191 at 15. It asserts that “introduction,” as 10 used in claim 1, refers to this separate step. Id. But as explained in my PI Order, “[t]his portion of 11 the specification, which is also the subject of a separate claim in the patent, does not use the term 12 ‘introduction’ but instead states that nucleotides are ‘brought into contact with the target.’” PI 13 Order at 6 (citing ‘973 patent 6:19-24, 88:1-12). Although the specification does detail a two-step 14 process of first adding nucleotides to a reaction mixture and then removing non-incorporated 15 nucleotides prior to detection, it does not necessarily follow that claim 1 is directed to this process. 16 Indeed, the patent includes several claims that clearly reference this process, all of which repeat 17 the phrase “brought into contact with the target” and make clear that the method described 18 includes “a first step and a second step.” See ’973 88:1-36. Claim 1, in contrast, makes no 19 reference to these two steps and does not use the phrase “brought into contact.” See ’973 patent at 20 86:24-56. 21 BGI’s remaining arguments are no more persuasive. BGI argues that the common 22 dictionary definition of “introduction” -- “to put something or someone in a place among or 23 between other things or persons” -- is consistent with its proposed construction in which 24 “introduced” refers to adding nucleotides to a reaction mixture. Dkt. No. 191 at 17. But this 25 definition is also consistent with Illumina’s proposed construction, in which “introduced” refers to 26 incorporating a complementary nucleotide into a growing strand. BGI also takes issue with 27 Illumina’s citation to a sentence in the specification that uses the phrase “the incorporation of said 1 into said growing complementary polynucleotide,” arguing that Illumina “offers no reasons why a 2 person of ordinary skill would focus on this particular sentence to the exclusion of everything else 3 in the rest of the disclosure.” Dkt. No. 191 at 17. But as noted in my PI Order, this passage 4 provides an example of the term “introduction” being used “in a way very similar to, if not 5 interchangeably with, the word ‘incorporation.’” PI Order at 6. In contrast, BGI does not identify 6 any use of the word “introduction” in the patent suggesting that it is meant to be used 7 interchangeably with the phrase “brought into contact,” as it proposes. Further, BGI’s citation to 8 the deposition of Dr. Xiaohai Liu does not confirm its proposed construction. Dr. Liu’s testimony 9 acknowledges that nucleotides must be brought into contact with a reaction mixture before they 10 can be incorporated into a growing strand, but does not indicate that claim 1’s use of the term 11 “introduction” refers to this step. See (Dkt. No. 191-6) Milowic Decl., Ex. E at 211:13-212:17, 12 222:13-225:23. 13 Finally, BGI’s argument that the step of removing the blocking group must occur before 14 the step of adding new nucleotides to the reaction mixture fails because, for the reasons outlined 15 above, I have concluded that the term “introduction of the next complementary nucleotide” refers 16 to the incorporation of a complementary nucleotide into the growing strand, not to the addition of 17 nucleotides to the reaction mixture. As a result, claim 1 does not appear to include any step or 18 requirement related to the timing of the addition of nucleotides to the reaction mixture. 19 For these reasons, I adopt Illumina’s proposed construction. 20 B. “monitoring the sequential incorporation of complementary nucleotides” 21 Patent/Term Illumina’s Proposal BGI’s Proposal 22 “monitoring the sequential No construction necessary. sequentially incorporating 23 incorporation of labeled nucleotides and complementary monitoring their incorporation 24 nucleotides” over multiple cycles in a sequencing by synthesis 25 ’973 Patent: claim 1, 13 reaction 26 27 BGI argues that the term “monitoring the sequential incorporation of complementary 1 monitoring their incorporation over multiple cycles in a sequencing by synthesis reaction.” Dkt. 2 No. 191 at 10. Illumina argues that BGI’s proposed construction inappropriately creates two 3 limitations not included in the claim language: (1) that labeled nucleotides must be used; and (2) 4 that the labeling must occur prior to incorporation. Dkt. No. 184 at 13. Illumina further argues 5 that the language “over multiple cycles in a sequencing by synthesis reaction” is ambiguous and 6 unnecessary. 7 1. “labeled nucleotides” 8 BGI argues that this term should be construed to require the use of “labeled nucleotides” 9 arguing that this limitation is “at the heart of” the ’973 patent’s invention and can therefore be read 10 into the claims. See Dkt. No. 191 at 10-11. BGI’s primary support for its position is that in the 11 preferred embodiment of the ’973 patent, labeled nucleotides are used to detect the type of 12 nucleotide incorporated into the growing sequence. See id. BGI also notes that the specification 13 repeatedly references the use of labels and of detecting labels and asserts that, as a result, “the use 14 of labeled nucleotides is more than a preferred embodiment. Labeled nucleotides are central to the 15 performance of the claimed sequencing by synthesis method.” Dkt. No. 191 at 12. It argues that 16 it is therefore appropriate to read its proposed “labeled nucleotide” limitation into the claims. 17 While the Federal Circuit “has narrowly construed claim terms in light of the preferred 18 embodiment when the patent has described the preferred embodiment as the invention itself,” 19 SunRace Roots Enter. Co. v. SRAM Corp., 336 F.3d 1298, 1305 (Fed. Cir. 2003), here review of 20 the specification and the preferred embodiment do not indicate that the use of labeled nucleotides 21 is fairly characterized as the invention itself, as BGI contends. As noted in my PI Order, and 22 above, “[t]he focus of the patent is on the use of a blocking group to prevent new nucleotides from 23 binding.” PI Order at 5. While the claimed method involves detecting the type of nucleotide 24 incorporated into the growing strand, the precise means of detecting the nucleotide type is not the 25 focus of the invention. This is reflected in the disputed language of claim 1, which does not 26 specify a particular method for detecting the nucleotide type and instead states only that the 27 method comprises “monitoring the sequential incorporation of complementary nucleotides.” ’973 1 patent’s preferred embodiment, this alone cannot justify reading a limitation into the claims. See 2 MasterMine Software, Inc. v. Microsoft Corp., 874 F.3d 1307, 1310 (Fed. Cir. 2017) (“[W]hile we 3 read claims in view of the specification, of which they are a part, we do not read limitations from 4 the embodiments in the specification into the claims.”); SRI Intern v. Matsushita Elec. Corp. of 5 America, 775 F.2d 1107, 1121 n.14 (Fed. Cir. 1985) (“That a specification describes only one 6 embodiment does not require that each claim be limited to that one embodiment”). And, while it 7 is true that the use of labeled nucleotides is a necessary part of the preferred embodiment because 8 it fulfills the required monitoring or detection step, this does not preclude the use of some other 9 process to detect the nucleotide type instead. The patent specification and claim language do not 10 support BGI’s position that the use of “labeled nucleotides” can fairly be described as “the 11 invention itself” and do not justify reading this limitation into the claims. 12 Review of the claim language, which BGI also points to, only supports this conclusion. 13 BGI argues that the patent claim language indicates that a “labeled nucleotide” must be used 14 because claim 1 “recites that the label can be attached to the R’ moiety of the blocking group, 15 which is an embodiment described in the specification” while “claim 2 recites that the label is 16 attached to the base, another embodiment in the specification” and that “in all cases, there is a 17 label attached to the nucleotide before incorporation.” Dkt. No. 191 at 13. However, claim 1 does 18 not require a label to be attached to the R’ moiety of the blocking group – rather a detectable label 19 is listed as one of several alternative options for R’. See ’973 patent at 86:43-46. Dependent 20 claim 2 does specifically require that the nucleotide “comprises a base linked to a detectable 21 label,” but this primarily highlights that there is no specific labeling requirement in claim 1. 22 Indeed, as Illumina points out, given the “presumption that distinct claims, particularly an 23 independent claim and its dependent claim, have different scopes,” see World Class Tech. Corp. v. 24 Ormco Corp., 769 F.3d 1120, 1125 (Fed. Cir. 2014), claim 2’s specific detectable label 25 requirement reaffirms the idea that claim 1 does not include such a limitation. 26 The parties dedicate much of their briefing on this term to arguing over whether the ’973 27 patent discloses examples of detecting the nucleotide type through methods besides labeled 1 seem to agree that there are other methods for detecting a nucleotide type that do not involve the 2 use of labeled nucleotides and that these would have been known to a person of skill in the art at 3 the time of the invention. There is also no meaningful dispute that none of these methods are 4 specifically disclosed in the embodiments of the patent. In sum, the parties’ arguments back in 5 forth on these points do not meaningfully move the needle. The primary issue remains whether 6 the “labeled nucleotide” limitation disclosed in the patent’s embodiments should be imported to 7 the claims. For the reasons discussed above, I conclude that such a limitation is not appropriate. 8 2. “over multiple cycles in a sequencing by synthesis reaction” 9 Illumina opposes adding the phrase “over multiple cycles in a sequencing by synthesis 10 reaction,” asserting that the phrase introduces further terms without providing any additional 11 clarification and would likely only serve to confuse a jury. Dkt. No. 184 at 16. BGI argues that 12 there is no meaningful dispute that the term refers to the sequential incorporation of nucleotides 13 over multiple cycles in a sequencing by synthesis reaction and that this proposed construction 14 should be adopted as undisputed. Dkt. No. 191 at 10. In its reply, Illumina responds that the 15 phrase “sequencing by synthesis” is ambiguous, that BGI’s expert has said the phrase is 16 ambiguous, and that BGI’s expert has not been able to coherently explain what it is supposed to 17 add to BGI’s construction. Dkt. No. 195 at 5. In its sur-reply, BGI argues that its expert, Metzker, 18 explained that he understands the term sequencing by synthesis, in this context, to refer to the 19 “cyclic reversible termination” method recited in the claims. Dkt. No. 199 at 4. 20 I agree with Illumina that adding the proposed language is unnecessary and potentially 21 confusing. BGI does not make a strong argument why this additional language is needed. And, 22 while it appears that there is no real dispute between the parties that the ’973 patent claims a 23 method that involves a sequencing by synthesis reaction, the parties also seem to agree that the 24 term sequencing by synthesis is generally “ambiguous” and can mean different things in different 25 contexts. It does not appear that adding this language is likely to clarify the meaning of the 26 relevant term and could potentially introduce additional and unnecessary ambiguity. 27 For the reasons discussed above, I conclude that no construction is necessary for the term C. “wherein at least one incorporation is of a nucleotide having a removable 3’ – 1 OH blocking group covalently attached thereto” 2 Patent/Term Illumina’s Proposal BGI’s Proposal 3 “wherein at least one No construction necessary. indefinite 4 incorporation is of a nucleotide having a 5 removable 3’ – OH blocking group covalently 6 attached thereto” 7 ’973 Patent: claim 1, 13 8 BGI argues that the term “wherein at least one incorporation is of a nucleotide having a 9 removable 3’ – OH blocking group covalently attached thereto” is indefinite. Dkt. No. 191 at 20. 10 It contends that the phrase “at least one” appears to mean “one or more” but argues that this does 11 not make sense within the context of the claimed method, because the claimed method only works 12 if all of the incorporated nucleotides have a removable blocking group. Id. Illumina argues that 13 BGI’s indefiniteness claim is improper because BGI failed to disclose it in its invalidity 14 contentions, as required under the local patent rules. Dkt. No. 184 at 16. If I consider the 15 argument, it further argues that the term is not indefinite because it is straightforward and nothing 16 about it would “fail to inform, with reasonable certainty, those skilled in the art about the scope of 17 the invention.” Dkt. No. 184 at 19 (quoting Nautilus, Inc. v. Biosig Instruments, Inc., 572 U.S. 18 898, 901 (2014). For the reasons discussed below, I conclude that BGI’s indefiniteness challenge 19 with regard to this term is improper and, even if considered, fails on the merits. 20 1. Compliance With Patent Local Rules 21 Illumina asserts that I should disregard BGI’s indefiniteness challenge with respect to this 22 term because BGI failed to disclose it in its invalidity contentions, as required by Local Patent 23 Rule 3.3(d). Dkt. No. 184 at 16. BGI does not meaningfully dispute that it failed to disclose this 24 position in its invalidity contentions, but argues that I have discretion to consider the argument and 25 should do so because BGI disclosed this challenge during the claim construction meet and confer 26 process. Dkt. No. 191 at 21-22. 27 Patent Local Rule 3-3 requires that, no later than 45 days after service of the plaintiff’s 1 “disclosure of asserted claims and infringement contentions,” a defendant serve invalidity 2 contentions that contain, among other disclosures, “[a]ny grounds of invalidity based on 35 U.S.C. 3 § 101, indefiniteness under 35 U.S.C. § 112(2) or enablement or written description under 35 4 U.S.C. § 112(1) of any of the asserted claims.” Local Patent Rule 3.3(d). There is no meaningful 5 dispute that BGI did not comply with this requirement with regard to the disputed term. BGI 6 attempts to argue that it put Illumina “on notice that the asserted claims of all three asserted 7 patents are invalid for indefiniteness in its Preliminary Invalidity Contentions,” because it 8 disclosed other indefiniteness positions regarding other terms. Dkt. No. 191 at 22; see e.g. 9 Milowic Decl., Ex. K at 22. But BGI cannot preserve the right to make a specific indefiniteness 10 argument simply by making other, different indefiniteness arguments regarding the same patent. 11 Cf. Finjan v. Proofpoint, Inc., Case No. 14-cv-03227-PSG, 2016 WL 791792, at *3 (N.D. Cal. 12 Dec. 23, 2015) (rejecting argument that defendant had “generally reserved its right to assert claims 13 as invalid under Section 101” by making “exemplary claims,” and explaining that the 14 requirements of Patent Local Rule 3-3(d) “would be a nullity if parties could address it with a 15 broad reservation”). 16 Because BGI did not timely disclose its indefinite position regarding this term, the 17 question is whether I should consider BGI’s challenge despite this failure to disclose. Illumina 18 argues that I should not, noting that the Patent Rules are designed to “‘require parties to crystallize 19 their theories of the case early in the litigation’ so as to ‘prevent the “shifting sands” approach to 20 claim construction.’” Dkt. No. 184 at 18 (quoting O2 Micro Int’l Ltd. v. Monolithic Power Sys., 21 Inc., 467 F.3d 1355, 1364 (Fed. Cir. 2006). It points to various examples in which courts in this 22 district have stricken indefiniteness positions not disclosed in the defendant’s invalidity 23 contentions. Dkt. No. 184 at 17; see also Finjan, 2015 WL 9460295, at *3-4 (striking 24 indefiniteness challenges not raised in invalidity contentions; Silicon Labs., Inc. v. Cresta Techn. 25 Corp., No. 14-cv-03227-PSG, 2016 WL 791792, at *3 (N.D. Cal. Mar. 1, 2016) (striking 26 indefiniteness challenges not timely raised and noting that “the disclosure requirements of this 27 district’s patent local rules are not optional”). And it notes that if BGI wanted to add this 1 showing of good cause.” Patent L.R. 3-6. Finally, Illumina argues that, while BGI disclosed an 2 indefiniteness position regarding this term during the claim construction meet and confer process, 3 it did not clearly lay out the basis for its challenge as it would have done if disclosed in its 4 invalidity contentions, making it difficult for Illumina to meaningfully respond to BGI’s position 5 until after BGI properly explained it in its responsive claim construction brief. Dkt. No. 195 at 9. 6 BGI responds that “the Patent Local Rules are ‘not a straitjacket into which litigants are 7 locked from the moment their contentions are served. There is a modest degree of flexibility, at 8 least near the outset.’” Dkt. No. 191 at 23 (quoting 24/7 Customer, Inc. v. Liveperson, Inc., No. 9 3:15-cv-02897 JST KAW, 2016 WL 6673983, at *3 (N.D. Cal. Nov. 14, 2016) (citations 10 omitted)). It asserts that Illumina would not be prejudiced if I consider this indefiniteness 11 challenge because BGI disclosed it was making such a challenge in its claim construction 12 materials and specifically discussed the phrase “at least one” with Illumina during the parties’ 13 meet and confer. Dkt. No. 191 at 21-22. It further notes that Illumina failed to object to this 14 indefiniteness challenge until the day before Illumina’s claim construction briefing was due. Id. at 15 21. 16 I conclude that BGI has waived the right to assert this indefiniteness challenge. BGI is 17 correct that there is some flexibility within the Patent Local Rules and a defendant is not 18 necessarily “locked” into their contentions the moment they are served. However, the Patent 19 Local Rules lay out a particular process and standard for amending contentions that BGI has not 20 followed, allowing a party to amend invalidity contentions “by order of the Court upon a timely 21 showing of good cause.” Patent L.R. 3-6. Patent Local Rule 3-6 suggests three potential bases to 22 support a showing of good cause: (1) a claim construction from the court contrary to the party’s 23 proposed construction; (2) the discovery of material, prior art, despite earlier diligent search; and 24 (3) discovery of nonpublic information not previously discovered despite diligent efforts. Id. And 25 the Federal Circuit has noted that parties must “proceed with diligence in amending [their 26 infringement and invalidity contentions] when new information comes to light in the course of 27 discovery.” O2 Micro, 467 F.3d at 1366. 1 “good cause” to do so. It offers no explanation as to why it did not include this challenge in its 2 initial invalidity contentions and has not sought leave of court to make any such amendment, 3 undermining a potential argument that it has diligently sought to amend. Because I conclude that 4 BGI has not made a showing of “good cause” to amend its invalidity contentions, and did not 5 disclose this indefiniteness challenge in its preliminary contentions, BGI’s challenge is improper. 6 2. Merits of Indefiniteness Argument 7 Even if I consider BGI’s indefiniteness challenge on the merits, I conclude that BGI has 8 failed to carry its burden of demonstrating that the disputed term -- “wherein at least one 9 incorporation is of a nucleotide having a removable 3’ – OH blocking group covalently attached 10 thereto” -- is indefinite. 11 “[A] patent is invalid for indefiniteness if its claims, read in light of the specification 12 delineating the patent, and the prosecution history, fail to inform, with reasonable certainty, those 13 skilled in the art about the scope of the invention.” Nautilus, 572 U.S. at 901. BGI argues that the 14 disputed term is indefinite because the phrase “at least one” appears to mean “one or more,” but 15 for Illumina’s claimed method to work, “all of the incorporated nucleotides must have a 16 removable blocking group.” Dkt. No. 191 at 20. It contends that the plain meaning of the term is 17 therefore inconsistent with the claimed method and is irredeemably ambiguous. Id. at 20-21. It 18 asserts that the claim language would include within its scope a method where “one nucleotide has 19 a particular reversible 3’-OH block, and the others have no 3’-OH block at all.” Dkt. No. 199 at 5. 20 I conclude that the disputed claim, when read in light of the specification, is sufficiently 21 clear in its scope that it is not indefinite. The ’973 patent discloses a method of using a particular 22 kind of blocking group in a sequencing by synthesis process to incorporate nucleotides into a 23 growing strand, one at a time, so the nucleotide types can be detected. As I have repeatedly noted, 24 “[t]he focus of the patent is on the use of a blocking group to prevent new nucleotides from 25 binding,” such as in a sequencing by synthesis method. PI Order at 6. A person of ordinary skill 26 in the art reading the claims, in light of the specification, would understand that the scope of the 27 method is limited to processes in which the relevant type of blocking group is used in a 1 BGI suggests that the phrase “at least one” is in conflict with the claimed method and the 2 specification because the method only works if all of the incorporated nucleotides have a 3 removable blocking group. Dkt. No. 191 at 20. But Illumina points out that the patent might 4 include a method where “at least one” incorporation is of a nucleotide containing the specific 3’ – 5 OH blocking group listed in claim 1, while other incorporated nucleotides have a different kind of 6 blocking group attached. Dkt. No. 195 at 9-10. It also notes that “the method could be performed 7 with one nucleotide having a ‘removable 3’ – OH blocking group covalently attached thereto,’ and 8 then terminated when a nucleotide that did not contain a removable blocking group was finally 9 incorporated.” Id. at 10. It does not appear that the phrase “at least one” would confuse a person 10 of ordinary skill in the art regarding the proper scope of the ’973 patent. Accordingly, the term is 11 not indefinite. 12 For the reasons described above, I conclude that no construction is necessary for this term. 13 D. “wherein said molecule may be reacted to yield an intermediate in which each R” is exchanged for H” 14 15 Patent/Term Illumina’s Proposal BGI’s Proposal 16 “wherein said molecule may No construction necessary. indefinite be reacted to yield an 17 intermediate in which each R" is exchanged for H” 18 ’444 Patent: claim 1, 3 19 20 BGI argues that the term “wherein said molecule may be reacted to yield an intermediate 21 in which each R" is exchanged for H” is indefinite because claim 1 of the ’444 patent recites two 22 different formulas that cover azidomethyl, but this limitation only applies to one of them, making 23 the scope of the claim unclear. I disagree and conclude that a person of ordinary skill in the art 24 would not be confused regarding the scope of what is claimed. 25 Claim 1 of the ’444 patent lists five possible chemical groups that can fulfill the claim’s 26 “Z” structure. ’444 patent at 86:4-7. The parties agree that azidomethyl fits under two of these 27 five formulas, —C(R’)2—N(R")2, which the parties refer to as formula (2) and —C(R’)2—N3, which 1 describes how a blocking group is chemically reacted and removed. See id. at 86:31-35. In the PI 2 Order, I held that this disputed limitation does not apply to azidomethyl, as represented by formula (5), 3 because “[u]nlike the other enumerated structures in claim 1, there is no symbol for R" in this 4 structure, which indicates that the limitation regarding R" does not apply to the azido structure.” PI 5 Order at 8. In my analysis, I acknowledged that azidomethyl can fall within the structure of formula 6 (2), but explained that “claim 1 also provides for the more specific structure, —C(R’)2—N3, in which 7 —N3 takes the place of N(R")2” and noted that “[t]he claim language and patent specification 8 repeatedly describe an azido group as C(R’)2—N3.” PI Order at 8. 9 BGI argues that, because the disputed limitation does not apply to formula (5) but does 10 apply to formula (2), “depending on which formula is selected for azidomethyl, the scope of the 11 claim is different.” Dkt. No. 191 at 5. I disagree. As previously explained in my PI Order, I 12 conclude that the more specific construction of formula (5) is intended to cover azidomethyl, 13 rather than formula (2). But even if we analyze azidomethyl under both formulas, the scope of the 14 claim is clear. As represented by formula (5), claim 1 covers a modified molecule as described by 15 the patent where the Z structure is azidomethyl and the remaining applicable claim limitations are 16 met. As I held in my PI Order, the disputed limitation “does not apply to instances where “Z” is 17 an azidomethyl,” meaning that a molecule where “Z” is azidomethyl would be covered by the 18 claims, assuming all other relevant limitations are met, even if it does not satisfy the final 19 limitation. PI Order at 8. That formula (2) can also describe an azidomethyl does not create an 20 ambiguity. That part of the claim covers a modified molecule with an azidomethyl Z structure that 21 does meet the final claim limitation, which is simply a subset of the molecules containing 22 azidomethyl that are covered by the formula (5) portion of the patent. And, that a molecule 23 containing an azidomethyl might satisfy the claim limitations under formula (5) but not formula 24 (2) does not mean the scope is unclear. The same molecule also would not satisfy the claim 25 limitations under formulas (1), (3), or (4), but BGI does not assert that this somehow creates 26 confusion as to what is covered. A person of ordinary skill in the art would not be confused by the 27 scope of the claims and whether a particular product infringes. 1 USA, Inc. v. Sandoz, Inc., 789 F.3d 1335, 1341 (Fed. Cir. 2015), the Federal Circuit found claims 2 that recited the term “molecular weight” indefinite because there are multiple formulas used to 3 calculate molecular weight but nothing in the claims, specification, or prosecution history 4 identified which formula to apply. Similarly, in Dow Chem. Co. v. Nova Chems. Corp., 803 F.3d 5 620, 633 (Fed. Cir. 2015), the Federal Circuit found claims indefinite where the claims recited “a 6 slope of strain hardening” but the patent failed to teach which of four unstated formulas to use for 7 measuring slope of strain hardening. The court explained that this made the claims indefinite, 8 stating that “[b]ecause the methods do not always produce the same results, the method chosen for 9 calculating the slope of strain hardening could affect whether or not a given product infringes the 10 claims.” Id. at 634. 11 Those cases are not analogous to the situation here. In Teva and Dow, the claims recited 12 ambiguous terms that required a person to pick one of several unstated, but generally known, 13 formulas to calculate a “molecular weight” or “a slope of strain hardening.” See Teva, 789 F.3d at 14 1341; Dow, 803 F.3d at 633. Here, instead, there is no such ambiguous term and the formulas at 15 issue serve a completely different purpose. The ’444 patent lists five different chemical groups – 16 represented by formulas – that can satisfy the Z structure in the claim. There is no ambiguity over 17 which formula to use – five alternative options are explicitly listed in the claim language and they 18 are all claimed in the patent. There is no need to guess which formula to apply – if a product 19 infringes the patent under any of the listed formulas it infringes the claims. 20 BGI’s contention that the final limitation term is indefinite because it is material to 21 patentability, but does not apply to azidomethyl, is not convincing. BGI takes issue with the fact 22 that, under formula (5), the final claim limitation does not apply, suggesting that this limitation 23 represents a “feature” of the invention without which the patent is “missing [a] key element.” Dkt. 24 No. 191 at 5-6. But BGI does not adequately explain how this relates to its indefiniteness 25 challenge or how this creates ambiguity about what falls within the scope of the patent. 26 The cases BGI cites in support are inapposite. In Trustees of Columbia Univ. in City of 27 New York v. Symantec Corp., 811 F.3d 1359, 1365, 1367 (Fed. Cir. 2016) the Federal Circuit 1 instructions from something that does not have machine code instructions” which made the claims 2 nonsensical. Here, in contrast, the disputed limitation is not nonsensical – it makes sense as 3 applied to four of the five possible chemical groups that can satisfy the “Z” structure. It is 4 plausible that the limitation is simply meant to apply to some, but not all, possible “Z” formulas, 5 as I concluded in my PI Order. BGI also cites to Hoffer v. Microsoft Corp., 405 F.3d 1326, 1329 6 (Fed. Cir. 2005), in which the Federal Circuit noted that when a “‘whereby’ clause states a 7 condition that is material to patentability, it cannot be ignored in order to change the substance of 8 the invention.” But the Federal Circuit analysis in Hoffer was not in the context of an 9 indefiniteness challenge; the court was considering whether it was mandatory that the limitation 10 apply to the claim. Here, BGI does not argue for a construction in which the disputed limitation 11 applies to formula (5) – an issue that I already addressed in a different context in my PI Order – 12 and so Hoffer is not on point. 13 BGI has failed to carry its burden of showing that the disputed limitation is indefinite. I 14 conclude that no construction is necessary for this term. 15 E. “that can be modified or removed to expose a 3’ OH group” 16 Patent/Term Illumina’s Proposal BGI’s Proposal 17 “that can be modified or No construction necessary. indefinite 18 removed to expose a 3’ OH group” 19 ’025 Patent: claims 1-21, 27- 20 29 21 The parties dispute the construction of the term “that can be modified or removed to 22 expose a 3’ OH group.” BGI argues that this term is indefinite “because the conditions for 23 modifying or removing the claimed azido protecting groups are not specified.” Dkt. No. 191 at 24 23. BGI’s challenge is based on the idea that there is an unstated “efficiency” limitation for the 25 removal step in the ’025 patent because Illumina has argued that the prior art “does not disclose 26 modification or removal of azidomethyl with the required ‘efficiency.’” Dkt. No. 191 at 23. 27 Illumina objects to this challenge on the basis that it is not stated in BGI’s invalidity contentions, 1 which instead identify this term as indefinite due to the allegedly unclear meaning of the term 2 “modified.” Dkt. No. 195 at 14. It argues that this challenge should be struck for failure to 3 comply with the Local Patent Rules. It further argues that BGI’s challenge fails on the merits 4 because there is no “efficiency” limitation in the patent. 5 1. Compliance With Local Patent Rules 6 BGI does not dispute that it did not disclose this indefiniteness theory in its invalidity 7 contentions. In its sur-reply, it argues, in a single sentence, that Illumina “has waived any 8 objection to the consideration of this term, for all the reasons discussed in BGI’s responsive brief.” 9 Dkt. No. 199 at 5. But BGI’s responsive claim construction brief does not address this issue 10 because it was first raised in Illumina’s reply brief. BGI offers no explanation or meaningful 11 response to Illumina’s assertion that BGI failed to properly disclose this theory in violation of the 12 Patent Local Rules. Indeed, unlike the challenge to the term “wherein at least one incorporation is 13 of a nucleotide having a removable 3’ – OH blocking group covalently attached thereto,” which 14 Illumina admits BGI at least raised during the claim construction meet and confer process, there is 15 no indication from either party that BGI disclosed the substance of this challenge prior to filing its 16 responsive claim construction brief. Indeed, Illumina’s opening brief addresses a completely 17 different dispute over the alleged ambiguity of the term “modified,” suggesting that Illumina did 18 not understand the substance of BGI’s challenge to this term prior to reviewing BGI’s responsive 19 filing. 20 By failing to disclose this indefiniteness argument in its invalidity contentions, BGI has 21 failed to comply with the Patent Local Rules. See NobelBiz, Inc. v. LiveVox, Inc., No. 13-cv- 22 1773-YGR, 2-15 WL 225223, at *8 (N.D. Cal. Jan. 16, 2015) (holding “that defendants have 23 failed to comply with the Patent Local Rules, and their indefiniteness argument was not properly 24 raised” where invalidity contentions identified particular term as indefinite without explanation). 25 As BGI has made no effort to explain or justify its failure to properly disclose this argument and 26 made no request to amend its invalidity contentions, I conclude that it has waived the right to raise 27 this challenge. 2. Merits Of Challenge 1 Even if I address BGI’s argument on the merits, I conclude that BGI has failed to show 2 that this term is indefinite. It argues that the term is indefinite because Illumina has suggested, in 3 other contexts, that the claims have an implicit “efficiency” requirement, but nothing in the patent 4 claims, specification, or prosecution history provides guidance on what constitutes “the proper 5 efficiency.” Dkt. No. 191 at 24. This argument has two primary flaws and does not demonstrate 6 that the claims are indefinite. 7 First, BGI’s argument stretches a reasonable interpretation of Illumina’s prior statements 8 regarding “efficiency.” Illumina has argued that the ’025 patent is not obvious because a person 9 of reasonable skill in the art would not have been motivated to combine the references of 10 Zavgorodny (teaching that an azidomethyl moiety is a suitable protecting group for the 3’ OH 11 position of nucleosides) with those of Tsien (describing a process of sequencing unknown DNA 12 involving the sequencing by synthesis method, including the labeling of nucleotides for detection 13 and the use of a protecting group at the 3’ – OH position of the nucleotide) because such a person 14 would not have thought that azidomethyl would meet the efficiency limitations described in 15 Tsien’s method. See Dkt No. 74-4 at 10-12; Intelligent Bio-Systems, Inc. v. Illumina Cambridge 16 Ltd., 821 F.3d 1359, 1363-1364 (Fed. Cir. 2016). As a result, Illumina has argued that the novel 17 use of azidomethyl in a sequencing by synthesis method was inventive and not invalid for 18 obviousness. Id. This argument has nothing to do with the actual efficiency of azidomethyl in a 19 sequencing by synthesis method, but only what expectations a person of ordinary skill in the art 20 would have had about whether such a method would be effective. Illumina’s statements do not 21 suggest that the ’025 patent contains an “efficiency” limitation. 22 Second, even if Illumina’s arguments did suggest such a limitation, BGI does not cite any 23 case in which a court has read in a limitation to a patent based solely on a patentee’s legal 24 arguments during litigation. BGI explains, at length, that no such limitation appears anywhere in 25 the patent claims, specification, or prosecution history. See Dkt. No. 191 at 24-25. But instead of 26 concluding that no such limitation exists, BGI points to this lack of a limitation as evidence that 27 the patent is indefinite. I reject this argument. That the ’025 patent does not delineate the 1 contours of an unstated “efficiency” limitation, of which there is no evidence anywhere in the 2 || patent claims, specification, or prosecution history, does not make the claims indefinite. 3 I conclude that no construction is necessary for this term. 5 I construe the disputed terms as follows: 6 Patent/Term Court’s Construction 7 “wherein the blocking group is removed | wherein the blocking group is removed before 8 prior to introduction of the next the next complementary nucleotide is complementary nucleotide” incorporated into a growing nucleotide strand 9 complementary to the target single-stranded *973 Patent: claim 1, 13 polynucleotide being sequenced 10 11 “monitoring the sequential incorporation | No construction necessary. of complementary nucleotides”
, det s 13 973 Patent: claim 1, 13
“wherein at least one incorporation is of | No construction necessary. 15 a nucleotide having a removable 3’ - OH blocking group covalently attached 16 thereto”
17 °973 Patent: claim 1, 13
18 “wherein said molecule may be reacted No construction necessary. 19 to yield an intermediate in which each R" is exchanged for H” 20 444 Patent: claim 1, 3 22 “that can be modified or removed to No construction necessary. expose a 3’ OH group” 23 °025 Patent: claims 1-21, 27-29 25 IT IS SO ORDERED. . f 26 Dated: November 24, 2020 a Te. Sriick □ United States District Judge 28