(admitted pro hac vice) (admitted pro hac vice) Jonathan E. Bachand. Nathanael R.

Transcription

1 Filed: August 12, 2015 On behalf of Patent Owner Illumina, Inc., by: Kerry S. Taylor Adrian C. Percer William R. Zimmerman (admitted pro hac vice) Edward R. Reines Michael L. Fuller (admitted pro hac vice) Jonathan E. Bachand Nathanael R. Luman Derek C. Walter KNOBBE, MARTENS, OLSON & (admitted pro hac vice) BEAR, LLP Main Street, 14 th Floor WEIL, GOTSHAL & MANGES, LLP Irvine, CA Redwood Shores Parkway Tel.: (949) Redwood Shores, CA Fax: (949) Tel.: (650) Fax: (650) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD ARIOSA DIAGNOSTICS, INC. Petitioner, v. ILLUMINA, INC. Patent Owner. IPR U.S. Patent 7,955,794 B2 ILLUMINA MOTION TO EXCLUDE ARIOSA EVIDENCE

2 I. RELIEF REQUESTED Pursuant to 37 C.F.R (c) and the Scheduling Order (Paper 15) at 3, Patent Owner Illumina, Inc., ( Illumina ) moves to exclude all of Exs , and and portions of Exs and 1046 submitted by Petitioner Ariosa Diagnostics, Inc. ( Ariosa ) and all arguments based thereon. Illumina timely objected to these exhibits on July 1, See Paper 46. II. SEVERAL OF ARIOSA S EXHIBITS ARE INADMISSIBLE Exs , , 1048 and 1049 should be excluded under FRE since Ariosa failed to discuss any of these exhibits. Use of these exhibits now would be improper incorporation by reference. See 37 C.F.R. 42.6(a)(3). Exs should be excluded under FRE , 802, and 901. These exhibits are irrelevant because they are not prior art. Also, Ariosa offers no evidence that these exhibits are what Ariosa purports them to be, they are offered to prove the truth of the matter asserted, and do not fall into any hearsay exception. Ex should be excluded under FRE Ariosa suggests Ex is the same as Figs. 1a-2d of the 810 application. But Ariosa interprets the 810 application by citing text in Ex not in the 810 application. Paper 44 at 12. Ex is a priority document of the 794 patent, not prior art. Use of Ex to redefine the disclosure of the 810 application is misleading and irrelevant. Ex contains numerous assertions by Ariosa s new expert that should 1

3 be excluded under FRE 106 and as incomplete, irrelevant, and misleading to the arguments in Ariosa s Petition or in Illumina s Patent Owner Response. Also, numerous assertions in Ex should be excluded under FRE 702 because they lack sufficient facts and data, and are not the product of reliable principles. Ex also contains numerous unexplained assertions that are irrelevant and misleading under FRE because they directly contradict the testimony of both experts in Ariosa s Petition. See, e.g., Invitrogen Corp. v. Clontech Labs., Inc., 429 F.3d 1052, 1080 (Fed. Cir. 2005) Dr. Cantor s declaration is also unreliable because it includes detailed discussions of documents that Dr. Cantor says he barely read. Ex at 198:3-199:16, 203: Dr. Cantor repeatedly opines on and mischaracterizes Dr. Kramer s testimony, but testified that he did not carefully or fully read that testimony. Id. at 89:7-20. Thus, portions of the Cantor declaration should be excluded under FRE 106 and as including irrelevant, misleading, and mischaracterized testimony. Further, Ariosa s use of Dr. Cantor to interpret Dr. Kramer s opinions (in contrast to offering his own opinions) is improper expert testimony, beyond the expertise of Dr. Cantor. It is evident that much of Ex. 1045, including 23, 27, 30, 31, 33, 35, 39, 43, 46, 51, 52, 58, 61, 63, and 65, represent an attempt by Roche/Ariosa to expand their page limit for attorney argument and not to provide proper or reliable expert testimony under FRE 701 and

4 Paras. 22, 30 and 31 are irrelevant under FRE 401. Dr. Cantor asserts in 22 that Figs. 4 and 2b disclose all elements of claim 1 on their own. This assertion was not in Ariosa s Petition and directly contradicts statements made by a prior expert. Paper 1 at 15-19; Ex at 103:5-9, 133: The same is true of Dr. Cantor s argument in 30 and 31 regarding washing applying to Part II of the invention disclosure. Paper 1 at 17; Ex at 130:25-131:7 and 149:8-13. Paras , 41-44, and 53 should be excluded under FRE 702. These paragraphs contain assertions of what was known and routine in the art in that are not supported by sufficient facts or data. Para. 28 provides one citation to support the first two sentences, but the remainder is completely unsupported. Paras. 29, 41, 42, 44, and 53 are completely unsupported. In 30, Dr. Cantor s supports his assertion of what the invention disclosure section discloses by citing to Fig. 4, which is not part of the invention disclosure section. Para. 43 should be excluded under FRE 403 because it mischaracterizes Dr. Kramer as testifying that in Figs. 4 and 2a-c, upstream probes would have identical universal primers. But Dr. Kramer only testified regarding the single upstream probe of Figure 2b and the single upstream probe of Figure 4. Ex at 206:9-208:2. Dr. Kramer was silent regarding the number of probes sharing identical universal priming sites in Figs. 4 and 2a-c. Dr. Kramer s only testimony regarding the number of probes in Figs. 4 and 2a-c makes clear that those figures 3

5 do not disclose more than 100 probes. Ex at 210:14-211:16, 237:23-238:12, 241:9-25, 254:6-20. Importantly, although 28-30, 41-44, and 53 purport to describe how a skilled artisan would understand the 810 application, these paragraphs never cite to the 810 application (Ex. 1012) itself for any disclosure. Para. 31 should be excluded under FRE and 702. Para. 31 cites Dr. Kramer s testimony that washing could be added to the Fig. 2 protocol in Part II of the 810 application. However, this citation is misleading as it ignores the many times Dr. Kramer expressly testified that washing was not actually present in the Fig. 2 protocol. See Ex at 137:7-21, 157:24-158:1, 161:12-17, 180:11-22, 181:6-183:6, and 186:5-8. Para. 31 also ignores Dr. Kramer s explanation why a skilled artisan reading the 810 application would understand that washing was not necessary to the Fig. 2 protocol. Id. at 176:15-178:25. Paras. 33, 34, and 38 should be excluded as irrelevant and misleading under FRE These paragraphs assert that the experimental strategies of the 810 application, including the teachings of the R33 phase, apply equally to all disclosed protocols. This assertion contradicts Ariosa s position in its Reply; Ariosa s prior two experts testified that it was unknown what protocol would be performed in the R33 phase. Ex at 86:17-87:2, Ex at 51:10-52:2, Ex Even then, the experts agreed that the only two protocols possible for the R33 phase were the one- and two-oligo protocols; there was no mention of the three-oligo 4

6 protocol. Ex at 82:15-84:2, Ex at 42:15-19, Ex Further, 31 frames Dr. Kramer s testimony (Ex at 116:18-117:7) as an admission that the grant application was intended to be part of the invention disclosure. However, 31 mischaracterizes Dr. Kramer s testimony by ignoring his subsequent testimony which undercuts Ariosa s assertion. Id. at 117:2-9. Paras. 36 and 40 should be excluded as irrelevant. Citing only to the R33 phase, these paragraphs assert that the 810 application discloses using a probe set having more than 100 probes. However, R33 does not expressly disclose more than 100 probes; instead Ariosa relies on R33 s statements as inherently teaching this claim element. Paper 1 at 16; Ex at 162:17-163:6. But Dr. Ward confirmed that R33 does not necessarily disclose a probe set having more than 100 probes because (1) he had no idea how many probes would be used in the R33 phase, and/or (2) R33 could be performed using separate probes in separate wells of a multi-well plate. Ex at 116:25-117:13, 103:10-104:13. Paras. 36 and 40 do not provide sufficient explanation to disregard Dr. Ward s admission. Further, paras and 49 are misleading and unsupported by evidence. Para. 40 asserts without support that R33 discloses at least two isoforms are tested per gene. Dr. Cantor states he disagrees with Dr. Kramer, but fails to rebut or even address the basis for Dr. Kramer s opinion. Dr. Kramer states that one gene could correlate to just one probe in the R33 phase, explaining that the 810 application 5

7 discloses testing only splicing isoforms that are associated with a disease. Ex at 289:25-291:9. He also states that when only one isoform of a gene is associated with a disease, only one probe is used per tested gene. Id. This means that R33 s testing of 50 to 100 genes, even if done in a single well, would not require 100 probes. Moreover, on cross, Dr. Cantor admitted a possible implementation of R33 would require only one probe per gene. Ex at 277:3-15. Paras. 46, 64, and 65 distort Dr. Kramer s testimony on the feasibility of the protocol in Fig. 2b. He testified that various steps of Fig. 2b were feasible, i.e., possible. Ex at 255:23-256:3. But Dr. Kramer s statement does not mean that the steps are actually disclosed in Fig. 2b, or would require no more than routine experimentation for one of ordinary skill. Further, this portion of Dr. Kramer s testimony is not relevant to the claims because he was referring to Fig. 2b, not a protocol that used more than 100 probes. Id. As Ariosa s own expert, Dr. Fu, testified, the 810 application does not provide enough guidance to the experiments in the scaled-up R33 portion of the 810 application. Ex at 77:2-79:11; 84:17-85:14; 86:17-87:6; 113:1-10; 124:15-125:7. On cross, Dr. Cantor discussed how large-scale protocols experience issues not present in smaller scale protocols. Ex :9-134:18, 253:4-7, 278:11-19; see also Ex at 28. Ariosa s other experts agree. Ex ; Ex ; Ex at 81:21-82:4, 85:11-86:3. Thus, 46 misrepresents the teachings of the 810 application and Dr. 6

8 Kramer s testimony, and ignores Ariosa s own prior expert testimony. Ex at 203: As such, 46 should be excluded under FRE 403 and 702. Para. 52 twice mischaracterizes Dr. Kramer s testimony by misleading and confusing assertions upon which 54 relies for its arguments. First, 52 asserts that Dr. Kramer admitted at 113:5-12 that the invention disclosure portion and grant application portion of the 810 application have a substantive relationship with each other. This citation is misleading and prejudicial because it omits Dr. Kramer s full testimony that the two sections are related by virtue of being usable for the same purpose, i.e., doing multiplex assays. Ex at 112: The fact that the two sections can be used for the same purpose is not a proper basis for concluding that Figs. 1b, 2b, 3 and 4 use the same protocol. And Dr. Kramer never says that the protocols of Figs. 1b, 2, 3 and 4 are the same. Second, 52 mischaracterizes Dr. Kramer s testimony at 161:18-162:5 as stating that washing is routine. However, 52 omits Dr. Kramer s immediately preceding testimony regarding Fig. 2b that it is not an automatic necessity that the wash step be put in there. And, it was left out of this figure. Ex at 161: This mischaracterization of Dr. Kramer s testimony is used in 54 to assert that Figs. 1b, 2b, 3 and 4 are the same in all material respects. This assertion contradicts Dr. Kramer s clear testimony that Fig. 2b does not have a wash step. Ex at 137:7-21, 157:24-158:1, 161:12-17, 176:24-178:25, 180:11-182:16. These 7

9 attempts to distort and confuse Dr. Kramer s testimony in 52 and 54 are misleading and prejudicial, and should be excluded under FRE 403. Paras are misleading, irrelevant, and are not proper expert testimony. Here, Dr. Cantor asserts that the Board rendered certain claim constructions in the Institution Decision. However, that Decision states it did not: We determine that, for purposes of this Decision, none of the other terms in the challenged claims requires express construction at this time. Paper 14 at 6. This contradiction highlights the fact that Dr. Cantor admitted letting Ariosa s attorneys write large portions of Ex (Ex :5-112:15) and that Dr. Cantor did not check that what Ariosa s attorneys wrote for him was accurate before signing it. This careless practice calls into question the credibility of all of Ex At a minimum, should be excluded under FRE 403 and 702 for this reason. Paras. 61 and 62 assert that the 810 application discloses probes with universal priming sites. But that is not what Claim 1 requires. Claim 1 recites each of said more than 100 different probes has identical universal priming sites Paras. 61 and 62 do not assert that the 810 application teaches more than 100 different probes having identical universal priming sites. The testimony of Dr. Kramer cited in 61 also does not support this assertion. Dr. Kramer only testified that the two probes shown in Fig. 2b and the two probes shown in Fig. 4 of the 810 application meet the definition of probe in Claim 1, (Ex at 206:14-8

10 208:23) and these protocols would test only a handful of genes. Id. at 237:23-238:12, 241:9-25. Dr. Ward concurred. Ex at 103:5-9 and 133: Further, the scaled-up protocol Ariosa relies on for disclosing more than 100 probes (R33) is silent regarding universal priming sites. Paras. 61 and 62 also state that using universal probes avoids biased signal amplification in PCR, (citing Ex at 6). However, this teaching was not cited in the Petition (see, e.g., Paper 1 at 16-17). Further, this cite is from the invention disclosure section of the 810 application, which does not disclose using multiple probes. Further, contrary to the claims, this quote does not require that all of the probes in a multiplex reaction contain identical universal priming sites. Both Drs. Cantor and Kramer agreed that some experiments could intentionally use multiple universal PCR primers and still avoid signal bias, e.g. to label different targets with different colors. Ex at 285:6-20; Ex at 244:10-245:12. Thus, 61 and 62 s assertion that the 810 application teaches each of said more than 100 different probes has identical universal priming sites is misleading and should be excluded under FRE 403. Para. 66 states that Fig. 2d differs from Fig. 4 only in that it contains three probes. However, as Dr. Ward testified, unlike Fig. 4, Fig. 2d does not contain a wash step. Ex at 130:25-131:7, 149:8-13. Para. 66 provides no evidence or reasoning for why Dr. Cantor arrives at the opposite conclusion from Dr. Ward s 9

11 conclusion. Since 66 is misleading, contradictory to prior expert testimony, and unsupported by sufficient facts or data, it should be excluded under FRE 403 and 702. Para. 69 states that the R33 phase of the grant application section of the 810 application would be understood to apply to the three-oligo protocol in Fig. 2d of the invention disclosure section. This is contradicted by the language of R33 itself, which states that the larger-scale R33 experiment would be based on either the one- or two-oligo approach from the R21 section of the grant part. Neither R33 nor the invention disclosure section mentions a three-oligo approach. This understanding was confirmed by Ariosa s first two experts. Ex at82:3-6, 83:16-87:6; Ex at 42:15-18, 51:20-52:13. Para. 69 does not provide any explanation for contradicting the plain language of the 810 application or Dr. Ward s and Dr. Fu s understanding of that language. As such, 69 is misleading and unsupported by sufficient facts or data, and should be excluded under FRE 403 and 702. Paras are cited in the Reply to support the proposition that the Petition identifies a relevant disclosure for Claims 2, 5-8, and 21. Paper 44 at But do not rely on the same disclosures, or even the same protocols, that are cited in the Petition against Claims 2, 5-8, and 21. Compare id. with Paper 1 at and 25. As an example, the Petition cites Fig. 1 and page 6 of

12 application (directed to a one-oligo protocol) against Claim 2. In contrast, 71 cites Figs. 2a-d and 4 (two-oligo protocol) of the 810 application against Claim 2. Since raise new validity theories that were not in the Petition, they are irrelevant to their use in the Reply and are misleading. They should be excluded under FRE Further, are misleading as they make no attempt to rebut Dr. Fu s testimony that the one-oligo disclosures cited in the Petition against Claims 2, 5-8, and 21 are not actually relevant to anticipation of the claims. Paper 31 at Thus, are not a proper Reply to Patent Owner s Opposition and should be excluded. See 37 C.F.R (b). Ariosa s use of portions of Ex is irrelevant and misleading so should be excluded under FRE Care should be taken when reviewing Ariosa s characterizations of Dr. Kramer s testimony as it is frequently presented unfairly, and should be considered with other sections of that testimony under FRE 106: Ariosa cites 38:13-39:4 as defining alternative splicing. Paper 44 at 7-8. Here Ariosa s attorney is reading the non-prior art Ex into the record, and Dr. Kramer accepts it. Nothing sets this as a proper definition in the relevant time frame. As Dr. Cantor himself explained, the understanding of alternative splicing changed over time. Ex at 124:18-127:19. Ariosa cites 51:4-12, 70:23-74:4, 134:12-136:9, 159:19-25, 254:22-257:1 to 11

13 claim that Dr. Kramer admitted that each step of the 810 application only required routine skill for the person of ordinary skill in Paper 44 at 6, 9, & However, Dr. Kramer stated that the protocols of Figs. 1a-1b, 2a-2d and 4 of the 810 application were feasible, i.e., possible. That a step might be possible does not mean that it requires only routine experimentation. Also, this testimony should be read with Dr. Kramer s explanation that even if the protocols of the 810 application were feasible at the small scales of Figs. 2a-2d and 4, skilled artisans implementing the protocols could not know if looking at a large number of targets would yield understandable results or even work at all (Ex at 254:6-20), because the special considerations for testing 100 targets would be daunting to those of skill in the art. Id. at 311:13-24; see also id. at 152:1-19, 210:18-212:25. It should also be read in light of Dr. Cantor s testimony that is in accord with Dr. Kramer s. Ex at 133:9-134:18, 278: Ariosa cites 279:18-280:2 as an admission that the 810 application inherently discloses using more than 100 probes. Paper 44 at 8. But in this citation Ariosa s attorney was not asking a question about what was actually disclosed in the 810 application; instead, he asked a hypothetical question that went beyond what was disclosed i.e., testing all isoforms of all 43 genes in Table I. Ex at 278:15-280:6. In contrast to this hypothetical question Dr. Kramer s testimony that what the 810 application actually discloses is testing only 12

14 a handful of the genes in Table I. Id. at 236:23-238:12. This use of the testimony is also misleading as Dr. Kramer counted all probes (279:12-16), not just those probes with identical universal priming sites as required by Claim 1. Ariosa cites Dr. Kramer at 272:25-273:7 as supporting that R33 applies to Fig. 2b. It does not. Further, Dr. Kramer s actual testimony should be viewed in light of his explanation of differences between Figs. 2b and Fig. 4 (Ex at 169:1-13, 176:15-179:5, 180:11-181:20), and his testimony that the similarity between Figs. 2b and 4 identified at 272:25-273:7 (testing splice junctions) is not present in Fig. 2d. Id. at 271:23-273:7. Ariosa asserts that 116:18-117:7 and 117:25-118:9 establish that Dr. Kramer agreed that the grant proposal section of the 810 application was intended as part of the invention disclosure section of the 810 application. Paper 44 at 10. But here Dr. Kramer stated that he was testifying with 15 years of hindsight and expertise that a skilled artisan would not have had at the relevant time. Ex at 116:17-117:9. Dr. Kramer s also testified that skilled artisans would realize that the 810 application just throws together three totally separate things that don t refer to each other. Id. at 213:22-214:13. Ariosa also cites 113:5-113:12 to support an argument that various protocols are interrelated. As explained with respect to Ex. 1045, 52, above, this exaggerates the relationship Dr. Kramer identified. 13

15 Ariosa cites 159:19-25 and 161:18-162:5 to assert that because Figures 2a- 2d could have a wash step they do have a wash step. Paper 44 at This assertion is misleading because it ignores Dr. Kramer s explicit testimony that the Figs. 2a-2d protocol does not include a wash step because the 810 application discloses that ligation achieves the same purpose as washing. Ex at 137:7-21; see also id. at 157:24-158:1, 161:12-17, 176:15-178:25, 180:11-22, 181:6-183:6, and 186:5-8; see also Ex at 130:25-131:7, 149:8-13. Ariosa cites 206:14-208:23 to imply that Dr. Kramer admitted that the 810 application teaches a protocol using more than 100 different probes having identical universal priming sites. This is misleading for the same reasons stated for 61-62, above. Further, Ariosa s assertion is undermined by Dr. Kramer s other contrary testimony. Ex at 285:6-20, 312:12-313:10. Ariosa cites 303:18-25 to incorrectly assert that Dr. Kramer agreed that Claim 1 does not require any specific degree of attachment. Paper 44 at 17. Ariosa mischaracterizes Dr. Kramer s testimony by ignoring Dr. Kramer s testimony that attached in the 794 patent is essentially permanent (Ex at 298:19-25) so as to keep targets intact under stringent washing conditions (id. at 284:25-285:5). Ariosa cites 73:25-76:6 to incorrectly assert that Dr. Kramer conceded that hybridization is sufficient for attachment. Paper 44 at 18. This mischaracterization ignores Dr. Kramer s further testimony that hybridization is 14

16 not necessarily acceptable (Ex at 75:13-20), that certain target RNA have the risk of being washed away (id. at 156:2-9, 320:4-23), and that immobilization merely by hybridization is unacceptable when assaying 100 targets due to the resulting errors (id. at 281:22-282:9). Ex should be excluded under FRE as irrelevant and misleading. Ariosa cites Ex to confuse the use of attached in the 794 patent, even though Dr. Cantor cites approvingly to the 794 patent s description of attachment as being stable enough to withstand denaturation of the hybridization complex and removal of the nonattached target nucleic acid. Ex at 59. Ex should be excluded under FRE as irrelevant to any issue raised in the Petition, and it is supplemental information filed without authorization from the Board. See 37 C.F.R Ariosa uses Ex to assert a new theory, not described in the Petition, of how the 946 publication constitutes prior art (Paper 44 at 23). This new theory is unsupported by any expert testimony. Exs and 1052 should be excluded under FRE for being used in a misleading way. Ariosa cites these exhibits to suggest that Patent Owner requested a change to priority, and was denied. Paper 44 at 23, n.9. In fact, only republication was denied in 2004 (see Ex. 1052); the request to revise the priority on the face of the patent (Ex. 1051) was granted in See, e.g., Ex at

17 Respectfully submitted, Dated: August 12, 2015 By: /Kerry Taylor/ Kerry Taylor, Reg. No. 43,947 William R. Zimmerman (admitted pro hac vice) Michael L. Fuller, Reg. No. 36,516 Jonathan E. Bachand, Reg. No. 67,884 Nathanael R. Luman, Reg. No. 63,160 KNOBBE, MARTENS, OLSON & BEAR, LLP Adrian C. Percer, Reg. No. 46,986 Edward R. Reines, (admitted pro hac vice) Derek C. Walter (admitted pro hac vice) WEIL, GOTSHAL & MANGES, LLP Attorneys for Patent Owner Illumina, Inc. 16

18 CERTIFICATE OF SERVICE I hereby certify that a true and correct copy of ILLUMINA MOTION TO EXCLUDE ARIOSA EVIDENCE is being served on August 12, 2015, via pursuant to 37 C.F.R. 42.6(e) per agreement of the parties, on counsel for Ariosa Diagnostics, Inc., at the addresses below: Greg Gardella cpdocketgardella@oblon.com OBLON, McCLELLAND, MAIER & NEUSTADT, LLP 1940 Duke Street Alexandria, VA Dianna L. DeVore ddevore@convergentlaw.com CONVERGENT LAW GROUP LLP 475 N. Whisman Road, Suite 400 Mountain View, CA David L. Cavanaugh David.cavanaugh@wilmerhale.com WilmerHale 1875 Pennsylvania Ave., N.W. Washington, D.C William W. Kim William.kim@wilmerhale.com Owen K. Allen Owen.allen@wilmerhale.com WilmerHale 950 Page Mill Road Palo Alto, CA Robert J. Gunther Jr. Robert.gunther@wilmerhale.com WilmerHale 7 World Trade Center New York, NY Dated: August 12, 2015 By: /Kerry Taylor/ Kerry Taylor, Reg. No. 43,947 Attorney for Patent Owner Illumina, Inc