Palese et al.v.Palese et al. V. Kawaoka et al. V. GARCIA-SASTRE et al. V. Palese et al.

Patent Trials and Appeals Board

Apr 30, 2013

09971372 - (J) (P.T.A.B. Apr. 30, 2013)

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.