Palese et al.v.Palese et al. V. Kawaoka et al. V. Garcia-Sastre et al. V. Palese et al.Download PDFPatent Trial and Appeal BoardApr 30, 201309616527 (P.T.A.B. Apr. 30, 2013) Copy Citation BoxInterferences@uspto.gov Paper 116 Telephone: 571-272-4683 ENTERED: 30 April 2013 UNITED STATES PATENT AND TRADEMARK OFFICE PATENT TRIAL AND APPEAL BOARD Patent Interference No. 105,819 (SCS) MOUNT SINAI SCHOOL OF MEDICINE (6,544,785; 6,649,372 and 7,384,774), Junior Party, v. WISCONSIN ALUMNI RESEARCH FOUNDATION (09/971,372), Senior Party. Before STEPHEN C. SIU, RAE LYNN P. GUEST, and DEBORAH KATZ, Administrative Patent Judges SIU, Administrative Patent Judge. Judgment – Merits – Bd.R. 127 In a concurrent paper, junior party MSSM’s Motion 4 alleging priority of invention over senior party WARF has been denied. It is ORDERED that judgment on priority as to the subject matter of Count 2, the sole count, is awarded to senior party WARF; FURTHER ORDERED that junior party’s claims 1, 2, and 4-30 of U.S. Patent 6,544,785; claims 1-4, 6-47, and 49 of U.S. Patent 6,649,372; Interference No. 105,819 2 and all claims of U.S. Patent No. 7,384,774, which correspond to Count 2, are herein cancelled; FURTHER ORDERED that the parties shall note the requirements of 35 U.S.C. 135(c) and Bd.R. 205; and FURTHER ORDERED that a copy of this judgment shall be entered into the files of Application 09/971,372; Patent 6,544,785; Patent 6,649,372; and Patent 7,384,774. cc: KEVIN E. NOONAN AND SARAH E. FENDRICK, McDonnell Boehnen Hulbert & Berghoff LLP, of Chicago, Illinois. ELLIOT M. OLSTEIN, RAYMOND J. LILLIE, AND ALAN J. GRANT, Carella, Byrne, Cecchi, Olstein, Brody & Agnello, of Roseland, New Jersey. BoxInterferences@uspto.gov Paper 115 Telephone: 571-272-4683 ENTERED: 30 April 2013 UNITED STATES PATENT AND TRADEMARK OFFICE PATENT TRIAL AND APPEAL BOARD Patent Interference No. 105,819 (SCS) MOUNT SINAI SCHOOL OF MEDICINE (6,544,785; 6,649,372 and 7,384,774), Junior Party, v. WISCONSIN ALUMNI RESEARCH FOUNDATION (09/971,372), Senior Party. Before STEPHEN C. SIU, RAE LYNN P. GUEST, and DEBORAH KATZ, Administrative Patent Judges SIU, Administrative Patent Judge. Decision – Priority – Bd.R. 125(a) A. Introduction The interference is before a merits panel of the Board for a decision on the question of priority. Both parties filed a substantive motion for judgment on the basis of priority of invention – Mount Sinai School of Medicine (“MSSM”) filed MSSM Motion 4 (Paper 90) and Wisconsin Alumni Research Foundation (“WARF”) filed WARF Motion 2 (Paper 93). Oral argument was held on March 20, 2013. Interference No. 105,819 2 Background The genome of influenza A virus consists of eight molecules of linear, single-stranded RNAs which encode ten polypeptides, including: the RNA- dependent RNA polymerase proteins (PB2, PB1, and PA), nucleoprotein (NP), matrix membrane proteins M1 and M2, two surface glycoproteins hemagglutinin (HA) and Neuraminidase (NA), nonstructural protein (NS1) and nuclear export protein (NEP) (MSSM Exhibit 1005, col. 3, ll. 43-52). Methods of generating infectious viral particles of influenza A virus are described including replicating infectious influenza A virus particles in the absence of helper virus by transfecting cells with expression vectors providing genomic or antigenomic vRNAs of influenza A virus (MSSM Exhibit 1005, col. 10, ll. 56-61). The subject matter of the count is directed to a method for generating infectious viral particles of an influenza virus including introducing into cultured cells expression vectors which direct the expression of the genomic or antigenomic vRNA segments of the virus, a nucleoprotein, and an RNA dependent polymerase in the absence of helper virus and culturing the cells wherein the viral particles are produced. B. Findings of Fact 1. Junior party MSSM is involved on the basis of U.S. Patent No. 6,544,785, issued April 8, 2003, based on application 09/616,527, filed July 14, 2000; U.S. Patent No. 6,649,372, issued November 18, 2003, based on application 09/724,412, filed November 28, 2000; and U.S. Patent No. 7,384,774, issued June 10, 2008, based on application 10/652,912, filed August 28, 2003. 2. Senior party WARF is involved on the basis of U.S. Patent Application 09/971,372 (“the ‘372 application”). Interference No. 105,819 3 3. WARF has been accorded benefit for the purpose of priority of U.S. Provisional Application 60/127,912, filed April 6, 1999 (“the ‘912 application”) (Paper 1 at 4). 4. MSSM has been accorded benefit for the purpose of priority of U.S. Provisional Application 60/143,645, filed July 14, 1999 (“the ‘645 application”). 5. Count 2, the sole count, is as follows: A method for generating in cultured cells infectious viral particles of an influenza virus, said method comprising: (a) introducing into cultured cells expression vectors which direct the expression of the genomic or antigenomic vRNA segments of said virus, a nucleoprotein, and an RNA dependent polymerase so that RNP complexes containing the genomic vRNA segments of said virus can be formed and said viral particles can be assembled within said cells in the absence of helper virus; and (b) culturing said cells wherein said viral particles are produced. 6. The claims of the parties which correspond to Count 2 are: MSSM: 6,544,785: 1, 2, and 4-30 6,649,372: 1-4, 6-47, and 49 7,384,774: all WARF: all 7. MSSM alleges that it conceived of the subject matter of Count as early as October 31, 1997 or no later than November 3, 1997 (Paper 90 at 1). 8. MSSM alleges that it actually reduced the invention to practice at least as early as November 3, 1997; June 28, 1999 (or no later than July 4, 1999); or July 7, 1999 (or no later than July 12, 1999) (Paper 90 at 1-2, 8- 10). Interference No. 105,819 4 9. MSSM alleges that it performed work directed toward reducing to practice an embodiment of Count 2 from a date prior to July 10, 1998 to any of an actual or constructive reduction to practice (Paper 90 at 2). C. Analysis MSSM, as the junior party, must demonstrate priority of invention by a preponderance of the evidence. Bd. R. 207(a)(2). The burden of showing something by a preponderance of the evidence requires the trier of fact to believe that the existence of a fact is more probable than its nonexistence before the trier of fact may find in favor of the party who bears the burden. Concrete Pipe & Products of California, Inc. v. Construction Laborers Pension Trust for Southern California, 508 U.S. 602, 622 (1993). “[P]riority of invention is awarded to the first party to reduce an invention to practice unless the other party can show that it was the first to conceive of the invention and that it exercised reasonable diligence in later reducing that invention to practice.” Hitzeman v. Rutter, 243 F. 3d 1345, 1353 (Fed. Cir. 2001). MSSM alleges that by as early as October 31, 1997, or in the alternative, no later than November 3, 1997 it conceived the invention and that as early as November 3, 1997, or at least as early as June 28, 1999 or July 7, 1999, it reduced to practice an embodiment of the Count. MSSM also alleges that during the period from a date prior to July 10, 1998 to each alleged actual reduction to practice, it performed work directed toward reducing to practice an embodiment of the Count (Paper 90 at 1-2). Interference No. 105,819 5 MSSM’s Alleged Conception and Reduction to Practice – October 31, 1997 and November 3, 1997 Conception is the “formation in the mind of the inventor, of a definite and permanent idea of the complete and operative invention.” Hybritech Inc. v. Monoclonal Antibodies, Inc., 802 F.2d 1367, 1376 (Fed. Cir. 1986). The “date of conception of a prior inventor’s invention is the date the inventor first appreciated the fact of what he made.” Dow Chem Co. v. Astro-Valcour, Inc., 267 F.3d 1334, 1341 (Fed. Cir. 2001). In other words, the inventor’s “failure to recognize that [the inventor] had produced [the invention], . . . is indicative that [the inventor] never conceived the invention.” Heard v. Burton, 333 F.2d 239, 243 (C.C.P.A. 1964). “In order to establish an actual reduction to practice, the inventor must prove that: (1) he constructed an embodiment or performed a process that met all the limitations of the interference count; and (2) he determined that the invention would work for its intended purpose.” Cooper v. Goldfarb, 154 F.3d 1321, 1327 (Fed. Cir. 1998). In addition, “there must be recognition and appreciation that the tests were successful for reduction to practice to occur.” Estee Lauder Inc. v. L’Oreal, S.A., 129 F.3d 588, 595 (Fed. Cir. 1997). Hence, in order to show either conception or actual reduction to practice by November 3, 1997, MSSM must show that the inventors recognized that they had produced the invention according to the count by November 3, 1997. MSSM Expert testimony – Dr. Andrew S. Pekosz Dr. Pekosz states that “the formation of plaque-like formations . . . indicates presence of an infectious virus, which can only form if RNPs are Interference No. 105,819 6 first produced” (MSSM Exhibit 1032, ¶ 30), and that the formation of RNP particles results from “[e]xpression in the cell of the NP and polymerase proteins along with the vRNA segments [of Influenza A virus]” (id.). Dr. Pekosz further states that the “failure [of Dr. Fodor] to observe a cytopathic effect . . . does not change my opinion that infectious influenza virus was produced” (MSSM Exhibit 1032, ¶ 17). However, the testimony of Dr. Pekosz does not support the contention that Dr. Fodor recognized and appreciated the invention of the count by November 3, 1997. While Dr. Pekosz proposes various theories as to why a cytopathic effect might not have been observed by the inventors on or around November 3, 1997 (MSSM Exhibit 1032, ¶ 17), Dr. Pekosz does not provide evidence demonstrating “that persons skilled in the art at the time of the [alleged] recognition would have recognized the existence of the relevant inventive features.” Invitrogen Corp. v. Clontech Laboratories, Inc., 429 F.3d 1052, 1065 (Fed. Cir. 2005). WARF Expert testimony – Dr. Yi Guan Dr. Yi Guan states that “plaque-like formations . . . would not have been considered by the person of ordinary skill in the art to show that recombinant influenza virus had been produced” (WARF Exhibit 2043, ¶ 11) and that “the skilled person would have expected recombinant influenza virus to be able to produce a cytopathic effect in cells infected with the supernatant produced by the cells” (WARF Exhibit 2043, ¶ 13). In support of this contention, Dr. Yi Guan cites “Lamb et al., (Ex. 2037, at 36-38); Hinshaw et al. (Ex. 2038, at page 3667, abstract); and Zerial et al. (Ex. 2039, at 9910)” (WARF Exhibit 2043, ¶ 9). Interference No. 105,819 7 Lamb states that “the virus . . . titre is determined by performing a plaque assay” (WARF Exhibit 2037, p. 41, section 2.4) but that, prior to quantifying a virus infectivity, virus stock is inoculated onto cell monolayers (WARF Exhibit 2037, p. 37), incubated with harvesting medium (WARF exhibit 2037, p. 38) and inspected for the presence of “c.p.e.” (WARF Exhibit 2037, p. 38). Hence, Lamb indicates that one of skill in the art would have expected to observe a cytopathic effect (or “c.p.e.”) in the presence of infectious viral particles (see WARF Exhibit 2037, “Abbreviations”). Conversely, one of skill in the art would have expected not to observe a cytopathic effect in the absence of infectious viral particles. Similarly, Zerial describes “an attempt to selectively inhibit the influenza virus” (WARF exhibit 2039, pp. 9909-9910) and to “inhibit the multiplication of influenza viruses in cell cultures” (WARF exhibit 2039, p. 9910). Such “antiviral effect . . . was based on the inhibition of the cytopathic effect (CPE) of . . . influenza virus on MDCK cells in culture” (p. 9910, “Materials and Methods”). Hence, Zerial indicates that the lack of a cytopathic effect indicates “antiviral effect,” implying the lack of infectious viral particles. Conversely, one of skill in the art would have expected the observance of a cytopathic effect without the lack (or in the presence) of infectious viral particles (see, also Lamb). We agree that the Lamb and Zerial references demonstrate that one of skill in the art would have understood that the lack of a cytopathic effect would have indicated the lack of infectious viral particles. Dr. Fodor’s testimony Dr. Fodor states that “on 3 November 1997, I . . . observed . . . plaque- like formations” and that he “knew that infectious influenza viral particles Interference No. 105,819 8 produce plaques” (MSSM Exhibit 1020, ¶ 24) but does not demonstrate or assert that he recognized and appreciated that the “plaque-like formations” allegedly observed were the definitive result of the generation of infectious influenza viral particles as required in the Count. Rather, Dr. Fodor testifies that he merely “knew” that infectious viral particles produce plaques. Dr. Fodor further states that he “did not see a cytopathic effect when [he] tested the . . . cell medium in cultures of MDBK cells” on November 3, 1997 (MSSM Exhibit 1020, ¶ 24). As described above, whether Dr. Fodor either conceived the invention or reduced the invention to practice on November 3, 1997 depends on whether Dr. Fodor recognized and appreciated that he had produced the invention by the purported date of November 3, 1997 in view of Dr. Fodor’s observance of “plaque-like formations” but the lack of a cytopathic effect. Following Dr. Fodor’s experiments on November 3, 1997, Dr. Fodor states that “[t]o reduce the number of plasmids . . . we decided to make cells that constitutively express one or more of the NP, PA, PB1 and PB2 viral proteins” (MSSM Exhibit 1020, ¶ 44) to “thereby reduce to 8 the number of plasmids we had to actually transfect into the cell in order to make virus” (MSSM Exhibit 1020, ¶ 47). Following this decision by Dr. Fodor, Dr. Fodor states that he engaged in “experiments performed during the time leading up to June 1999 [that were] aimed at . . . inducibly expressing one or more of the NP and polymerase proteins such as to reduce the number of plasmids required to produce infectious influenza virus” (MSSM Exhibit 1020, ¶ 26). According to Dr. Fodor, these experiments “leading up to June 1999” were largely unsuccessful (see, e.g., MSSM Exhibit 1020, ¶¶ 50, 61, 62, 79, 95, 114, 118, 121, 127, 135, 138, and 157 ) resulting in Dr. Fodor deciding “that trying to use cells that constitutively made one or more of the Interference No. 105,819 9 viral NP and polymerase proteins . . . was not going to work as well as we had hoped” (MSSM Exhibit 1020, ¶ 190) by June 28, 1999. This series of experimentation subsequent to MSSM’s alleged date of conception or reduction to practice of November 3, 1997, according to Dr. Fodor, was directed to producing nucleoprotein and polymerase proteins constitutively rather than performing all elements of the count (e.g., directing the expression of the genomic or antigenomic vRNA segments, a nucleoprotein, and a polymerase to form infectious viral particles). Such a modification in the goal of experimentation as well as the fact that the subsequent experimentation was deemed unsuccessful by June 1999 indicates that the inventive idea was not yet complete in the mind of the inventor at the earlier date of November 3, 1999. “A conception is not complete if the subsequent course of experimentation, especially experimental failures, reveals uncertainty that so undermines the specificity of the inventor’s idea that it is not yet a definite and permanent reflection of the complete invention as it will be used in practice.” Burroughs Wellcome Co. v. Barr Laboratories, Inc., 40 F.3d 1223, 1229 (Fed. Cir. 1994). Dr. Fodor states that in another experiment pertaining to virus particles performed on January 14, 1999, in which Dr. Fodor attempted to ascertain whether cells could support growth of infectious influenza virus, Dr. Fodor observed “there were a few patches with . . . ‘liquid plaques’ . . [but that Dr. Fodor] found no sign of a [cytopathic effect] on January 21, 1999, and terminated the experiment” (MSSM Exhibit 1020, ¶ 121). In that experiment, Dr. Fodor observed “plaques” but nevertheless concluded that the “cells did not support influenza replication” based on the absence of a cytopathic effect. Interference No. 105,819 10 In the experiment on January 14-21, 1999, Dr. Fodor observed plaque-like formations but did not observe a cytopathic effect and terminated the experiment based on these observations while concluding that the cells did not support influenza replication. In the November 3, 1997 experiment, Dr. Fodor states that he also observed a plaque-like formation but did not observe a cytopathic effect, a condition similar to that observed by Dr. Fodor in the January 14-21, 1999 experiment. Dr. Fodor does not explain why he arrived at a different conclusion (i.e., lack of support for the generation of infectious influenza virus particles) in the November 3, 1997 experiment. Hence, Dr. Fodor’s actions demonstrate that he did not consider that infectious viral particles had been produced on November 3, 1997. Rather, Dr. Fodor appears to have considered the observance of a lack of a cytopathic effect to indicate that cells do not support influenza replication based at least on the fact that Dr. Fodor “terminated the experiment” (as Dr. Fodor explicitly states that he did on January 21, 1999 during another experiment when plaques were observed but no cytopathic effect was seen at which time Dr. Fodor concluded that the cells “did not support influenza replication”). D. Conclusion For at least these reasons, MSSM has failed to demonstrate that it conceived of and/or reduced the invention to practice prior to WARF’s earliest accorded benefit date. Junior party MSSM has not established priority of invention over senior party WARF. It is therefore not necessary to consider senior party’s priority motion (WARF motion 2), MSSM’s opposition, or WARF’s reply. Interference No. 105,819 11 Because MSSM has failed to meet its burden in establishing conception of the subject matter of the count by any of its alleged date of conception of October 31, 1997 or November 3, 1997, or an actual reduction to practice by its alleged date of November 3, 1997, whether MSSM has established reasonable diligence from just prior to WARF’s conception to MSSM’s filing date or whether MSSM has established a reduction to practice on any of June 28, 1999 (or no later than July 4, 1999) or July 7, 1999 (or no later than July 12, 1999) is inconsequential. E. Order For the reasons given, it is ORDERED that MSSM’s motion 4 is denied; FURTHER ORDERED that WARF’s motion 2 is dismissed. cc: KEVIN E. NOONAN AND SARAH E. FENDRICK, McDonnell Boehnen Hulbert & Berghoff LLP, of Chicago, Illinois. ELLIOT M. OLSTEIN, RAYMOND J. LILLIE, AND ALAN J. GRANT, Carella, Byrne, Cecchi, Olstein, Brody & Agnello, of Roseland, New Jersey. Copy with citationCopy as parenthetical citation