Dressman et al.v.Berka et al.

Patent Trial and Appeal Board

Sep 6, 2013

12361690 (P.T.A.B. Sep. 6, 2013)

Mail Stop Interference Paper No.371
P.O. Box 1450 Entered: September 6, 2013
Alexandria, VA 22313-1450
BoxInterferences@uspto.gov
Tel: 571-272-4683
Fax: 571-273-0042

UNITED STATES PATENT AND TRADEMARK OFFICE
_______________

BEFORE THE PATENT TRIAL AND APPEAL BOARD

JOHNS HOPKINS UNIVERSITY
Junior Party
(Application 12/361,690)

v.

454 LIFE SCIENCES CORPORATION,
Senior Party
(Application 13/033,240),

Patent Interference No. 105,857 (JWB)

Before RICHARD TORCZON, SALLY GARDNER LANE, and
JACQUELINE WRIGHT BONILLA, Administrative Patent Judges.
BONILLA, Administrative Patent Judge.
JUDGMENT – 37 CFR § 41.127
Further to a concurrent Decision on Motions (Paper No. 370) denying Junior 1
Party JHU’s motion for judgment based on priority, and granting Senior Party 2
454’s motion for judgment based on priority, regarding Count 1, it is: 3
4
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ORDERED that judgment on priority as to Count 1 (the sole count in the 1
interference; Paper 1, p. 3) is entered against Junior Party JOHNS HOPKINS 2
UNIVERSITY; 3
FURTHER ORDERED that involved claims 1, 2, and 5-17 of Junior 4
Party’s U.S. application 12/361,690 (corresponding to Count 1) are herein 5
FINALLY REFUSED, 35 U.S.C. § 135(a); 6
FURTHER ORDERED that Junior Party JOHNS HOPKINS 7
UNIVERSITY is not entitled to a patent containing claims 1, 2, and 5-17 of U.S. 8
application 12/361,690, filed January 29, 2009; 9
FURTHER ORDERED that the parties note the requirements of 35 U.S.C. 10
§ 135(c) and Bd.R. 205 regarding the filing of settlement agreements; and 11
FURTHER ORDERED that a copy of this Judgment be placed in each of 12
the files of (1) JHU application 12/361,690, and (2) 454 application 13/033,240. 13

lb
Interference No. 105,857
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cc (e-mail):

For JHU:

Sarah A. Kagan, Esq.
Joseph M. Skerpon, Esq.
Banner & Witcoff, Ltd.
1100 13th Street, N.W., Suite 1200
Washington, DC 20005
E-mail: skagan@bannerwitcoff.com
E-mail: jskerpon@bannerwitcoff.com

Charles W. Calkins, Esq.
Cynthia B. Rothschild, Esq.
Kilpatrick Townsend & Stockton LLP
1001 West Fourth Street
Winston-Salem, NC 27101
E-mail: ccalkins@kilpatricktownsend.com
E-mail: crothschild@kilpatricktownsend.com

For 454:

R. Danny Huntington, Esq.
Sharon E. Crane, Ph.D., Esq.
Rothwell, Figg, Ernst & Manbeck, P.C.
607 14th St., N.W., Suite 800
Washington, DC 20005
E-mail: dhuntington@rfem.com
E-mail: scrane@rfem.com

Ivor R. Elrifi, Ph.D., Esq.
Mintz, Levin, Cohn, Ferris, Glovsky & Popeo, P.C.
One Financial Center
Boston, MA 02111
E-mail: IRElrifi@mintz.com

Mail Stop Interference Paper No. 370
P.O. Box 1450 Entered: September 6, 2013
Alexandria, VA 22313-1450
BoxInterferences@uspto.gov
Tel: 571-272-4683
Fax: 571-273-0042

UNITED STATES PATENT AND TRADEMARK OFFICE
_______________

BEFORE THE PATENT TRIAL AND APPEAL BOARD

JOHNS HOPKINS UNIVERSITY
Junior Party
(Application 12/361,690)

v.

454 LIFE SCIENCES CORPORATION,
Senior Party
(Application 13/033,240),

Patent Interference No. 105,857 (JWB)

Before RICHARD TORCZON, SALLY GARDNER LANE, and
JACQUELINE WRIGHT BONILLA, Administrative Patent Judges.
BONILLA, Administrative Patent Judge.
Decision on Motions - Bd.R. 125(a)
This interference is before a panel for decision on the question of priority. 1
An oral argument took place in this interference on August 7, 2013. Sarah Kagan 2
appeared for Junior Party John Hopkins University (JHU), and Danny Huntington, 3
Interference No. 105,857
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Sharon Crane, and Ivor Elrifi appeared for Senior Party 454 Life Sciences Corp. 1
(454). 2
I. The Motions 3
Two motions are pending before us: JHU Motion 3 (Paper 241) for 4
judgment based on priority, and 454 Motion 3 (Paper 250) for judgment based on 5
priority. For the reasons discussed below, we deny JHU Motion 3 and grant 454 6
Motion 3. 7
II. Background 8
The subject matter of this interference is directed to methods for analyzing 9
nucleic acid sequences comprising the use of aqueous microreactors in a water-in-10
oil emulsion, where a plurality of microreactors, each comprising a single DNA 11
fragment molecule, a single bead capable of hybridizing to the DNA fragment, and 12
reagents to perform DNA amplification. 13
The Board declared an interference between JHU’s U.S. Appl. No. 14
12/361,690 (‘690 application) and 454’s U.S. Appl. No. 13/033,240 (‘240 15
application). (Papers 1 and 18, Declaration and Redeclaration of Interference.) 16
The interfering subject matter is represented by a single Count 1, which is “JHU 17
claim 1 or 454 claim 52.” (Paper 1, p. 3.) JHU claim 1 is representative: 18
1. A method for analyzing nucleic acid sequences comprising: 19
(a) generating a plurality of molecules of a fragment of deoxyribonucleic 20
acid; 21
(b) delivering the plurality of molecules of the fragment of deoxyribonucleic 22
acid into aqueous microreactors in a water-in-oil emulsion such that a 23
plurality of aqueous microreactors comprise a single molecule of the 24
fragment of deoxyribonucleic acid, a single bead capable of hybridizing to 25
the fragment of deoxyribonucleic acid, and reagents necessary to perform 26
deoxyribonucleic acid amplification; 27
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(c) amplifying the fragment of deoxyribonucleic acid in the microreactors to 1
form amplified copies of said fragment of deoxyribonucleic acid bound to 2
beads in the microreactors; 3
(d) determining presence of amplified copies of said fragment of 4
deoxyribonucleic acid bound to a bead. 5
(Paper 7, p. 3.) Claims 1, 2, and 5-17 in JHU’s ‘690 application, as well as claims 6
52-66 in 454’s ‘240 application, correspond to the Count. 7
In relation to Count 1, the Board previously accorded benefit to the parties 8
of the filing dates of the following U.S. applications: 9
JHU: 12/361,690, filed Jan. 29, 2009; 10
10/562,840, filed June 22, 2006 (§371 Date; Nat’l Stage of PCT); 11
(via PCT/US04/15587, filed June 9, 2004); 12
60/525,859, filed Dec. 1, 2003; and 13
60/485,301, filed July 5, 2003. 14
454: 13/033,240, filed Feb. 23, 2011; 15
11,982,095, filed Oct. 31, 2007; 16
10/767,899, filed Jan. 28, 2004; 17
60/497,985, filed Aug. 25, 2003; and 18
60/476,592, filed June 6, 2003. 19
(Paper 1, p. 3; Paper 18, pp. 1-2.) 20
During the preliminary motions phase of this interference, the Board denied 21
JHU Motion 1 (Paper 45) attacking benefit accorded 454, as well as JHU Motion 2 22
(Paper 46) for judgment based on 35 U.S.C. § 135(b)(2). (Paper 236, pp. 2, 17.) 23
The Board also denied 454 Motion 1 (Paper 51) for benefit, as well as 454 24
Contingent Motion 3 (Paper 61) to add a claim to the 454 application. (Paper 236, 25
pp. 2, 17.) Thus, benefit accorded to the parties and claims corresponding to 26
Count 1 remain as mentioned above. 27
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In our previous decision, we also interpreted several phrases at issue in 1
Count 1. We interpreted “generating” in (a) of Count 1 to encompass fragmenting 2
an existing source of DNA, in addition to generating polymerase chain reaction 3
(PCR) products (Paper 236, p. 11). We also interpreted (a) as requiring the 4
generation of two or more of the same DNA fragment, not merely generating a 5
plurality of DNA fragments overall (id.). In addition, we interpreted “a single bead 6
capable of hybridizing” to a DNA fragment in (b) of Count 1 to encompass a bead 7
that is already hybridized to the DNA fragment, and not just a separate and distinct 8
bead that is not pre-hybridized to the DNA fragment (id. at 5). We further 9
interpreted (b) as referring to two or more microreactors, where each microreactor 10
comprises a single (one) DNA fragment, a single (one) bead, and amplification 11
reagents. 12
III. JHU Motion 3 for judgment based on priority 13
In its Motion 3, Junior Party JHU argues that it conceived, exercised 14
reasonable diligence, and actually reduced to practice the subject matter of Count 1 15
before June 6, 2003, 454’s earliest accorded benefit date (Paper 241, p. 2). 16
Alternatively, JHU argues that it conceived of the subject matter of Count 1 before 17
June 6, 2003, and exercised reasonable diligence through its constructive reduction 18
to practice on July 5, 2003 (id. at pp. 2-3). 19
In its Reply Brief, and during oral hearing, JHU indicated that it would focus 20
“solely on the issue of JHU’s June 5, 2003, prior conception coupled to JHU’s 21
diligence to its accorded constructive reduction to practice only one month later on 22
July 5, 2003” (Paper 262, p. 1). In our analysis here, we will likewise focus on 23
whether JHU establishes by a preponderance of the evidence that it conceived of 24
the subject matter of Count 1 by June 5, 2003, and engaged in reasonable diligence 25
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from that date until the filing of its provisional application Ser. No. 60/485,301 on 1
July 5, 2003.
1
2
JHU states that its inventors “documented a complete and corroborated 3
conception of the method of Count 1 in a PNAS manuscript (Ex 2042) that was 4
completed for publication on June 5, 2003” (Paper 241, p. 8). Exhibit 2042 does 5
indeed look to be a manuscript of a paper published in PROCEEDINGS OF THE 6
NATIONAL ACADEMY OF SCIENCES, USA (PNAS) on July 22, 2003 (Ex. 2026). 7
While Exhibit 2042 is not dated, the content of this manuscript reflects in relevant 8
part what is presented in the PNAS paper itself. 9
For example, both documents include a “Results” section including “Step 2–10
Preparing microemulsions,” which describes relevant aqueous compartment 11
(microreactors) where “only one in ~30 compartments contained a bead” and “one 12
in ~six compartments contacted a template [DNA fragment] molecule” (Ex. 2042, 13
p. 4; see also Ex. 2026, ¶ spanning pp. 8818-19). Both documents include Figure 1 14
and its figure legend, which depict and refer to “aqueous compartments (white 15
circles in the gray oil later) [that] contain an average of <1 template molecule and 16
<1 bead.” (Ex. 2042; Ex. 2026). The picture itself in Figure 1 presents a plurality 17

1
We note, however, that evidence cited by JHU does not sufficiently
establish that JHU conceived of the subject matter of Count 1 in the January–May
2003 time frame (Paper 241, pp. 6-8). The e-mail and attachment from Dr.
Vogelstein (inventor) to Dr. Kinzer (inventor) dated January 29, 2003 (Ex. 2039),
for example, do not adequately show that JHU inventors conceived of elements (a)
and (b) of Count 1 as interpreted above. Moreover, JHU offers insufficient non-
inventor evidence (testimony or otherwise) to corroborate conception by the JHU
inventors at that time (Paper 241, pp. 6-7). Generally, JHU does not specifically
explain, or offer sufficient evidence establishing, that JHU conceived of elements
(a) and (b) of Count 1 in February–May 2003. At best, JHU refers to a manuscript
(Ex. 2042) prepared and submitted in June 2003 to the PROCEEDINGS OF THE
NATIONAL ACADEMY OF SCIENCES, USA (PNAS). We address evidence relating to
this manuscript in the analysis below.
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(two) microreactors, where each contains one template DNA and one bead only. 1
Thus, the manuscript and PNAS paper describe (b) of Count 1. In addition, both 2
documents refer to using “PCR products” as templates in the described method, 3
which are generated as stated in (a) of Count 1. We find that the manuscript 4
presented in Exhibit 2042 and the PNAS paper (Ex. 2026) show that the JHU 5
inventors conceived of the subject matter of Count 1 as of June 6, 2003. 6
The PNAS paper itself corroborates conception by the JHU inventors by at 7
least this date because the PNAS paper states that the manuscript was “Contributed 8
by Bert Vogelstein, June 6, 2003” (Ex. 2026, p. 8817). While the manuscript in 9
Exhibit 2042 is undated, we believe that the evidence before us overall supports 10
the finding that Exhibit 2042 is a copy of the draft manuscript as submitted to 11
PNAS on June 6, 2003. 12
Moreover, a declaration by Scott E. Kern (Ex. 2023) sufficiently established 13
that Mr. Kern (a non-inventor) reviewed and provided comments to an earlier draft 14
of the manuscript no later than June 5, 2003 (Ex. 2023, p. 2 (stating “[o]n or prior 15
to June 5, 2003, I reviewed the manuscript”)). An exhibit to his declaration 16
includes a form listing comments, which Mr. Kern saved to his computer (id. 17
(stating that “[d]ata on my computer indicated that the last date on which this form 18
was printed or changed was June 5, 2003”); see also id. at Board pgs. 340-41). 19
For example, regarding Step 2 in the Results section, Mr. Kern suggested: 20
“5) Under ‘Step 2’ is stated ‘the number of beads could presumably be increased 21
by 30-fold’. Why not 100-fold? Or more? More than one bead per compartment 22
might work just fine. Why would the two-bead compartments need to be excluded 23
from the analysis?” (id. at Board pg. 340). In addition, Mr. Kern suggested: “13) 24
In Fig. 1, the first emulsion figure would benefit from the words “Oil” and 25
“Aqueous” being added, once each, in appropriate compartments” (id. at Board 26
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pg. 341). Thus, the evidence sufficiently establishes that, as of June 5, 2003, 1
Mr. Kern saw a version of a draft manuscript, i.e., a version earlier than the one 2
submitted to PNAS (Ex. 2042) on June 6, 2003, that described portions the Results 3
section and Figure 1 in the published PNAS paper that are relevant to conception, 4
as discussed above. Mr. Kern’s testimony sufficiently corroborates that JHU 5
inventors conceived of the subject matter of Count 1 as of June 5, 2003. 6
In its Opposition to JHU’s priority motion, 454 argues that “PNAS 7
authorizes further revisions after submissions are ‘communicated’, and JHU’s 8
evidence actually demonstrates that the manuscript was indeed revised after 9
submission” (Paper 257, pp. 8, 14). 454 does not explain or show how any portion 10
of the manuscript submitted to PNAS on June 6, 2003, or the draft version 11
reviewed by Mr. Kern by June 5, 2003, was revised or changed after submission in 12
a manner relevant to our analysis regarding conception. For example, 454 does not 13
allege nor establish that JHU revised the Results section or Figure 1 and figure 14
legend after submitting the manuscript to PNAS. 15
Thus, Junior Party JHU establishes by a preponderance of the evidence that 16
it conceived of the subject matter of Count 1 by June 5, 2003, i.e., one day earlier 17
than 454’s earliest accorded benefit date. JHU also meets its burden to establish 18
that JHU inventors were reasonably diligent for the month from June 5, 2003, until 19
the filing of provisional application No. 60/485,301 on July 5, 2003, i.e., JHU’s 20
constructive reduction to practice. See Appendix 3 “Diligence Chart” to JHU’s 21
priority motion (Paper 241, pp. 56-59). 22
IV. 454 Motion 3 for judgment based on priority 23
Because Junior Party JHU meets its burden to establish conception as of one 24
day before Senior Party 454’s earliest accorded benefit date, we analyze Senior 25
Party 454’s priority position and evidence. In its priority motion, 454 argues that it 26
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conceived of the subject matter of Count 1 by June 7, 2002, and thereafter reduced 1
to practice in January and February 2003, i.e., before JHU’s conception in June 2
2003 as discussed above (Paper 250, pp. 1-4, 8-9). 3
June 2002 – page 16 of Dr. Berka’s lab notebook 4
In relation to a conception in June 2002, 454 refers to page 16 of inventor 5
Dr. Berka’s notebook 119 (Ex. 1094) (Paper 250, pp. 9-11). This notebook page 6
includes a hand-drawn picture of an aqueous microreactor in a water-in-oil 7
emulsion comprising one bead, and describes “dilut[ing] to avg. SINGLE effective 8
copy/per bead.” Thus, the notebook page describes (b) in Count 1. 9
The notebook page by itself does not adequately establish, however, that the 10
454 inventors conceived of a relevant method comprising (a) in Count 1, i.e., 11
“generating a plurality of molecules of a fragment of deoxyribonucleic acid.” 12
At most, this page refers to “Sepharose-streptavidin HP beads” and states 13
“(see sequencing result in Notebook # ØØ76, pp. 52-59),” referring to pages in 14
another notebook of Dr. Berka (Ex. 1093). 15
As noted by 454, these other notebook pages describe “PRB1/Seq1 binding 16
to Streptavidin Sepharose HP” beads (Ex. 1093, p. 52; Paper 250, p. 9). 17
454 argues that “PRB1/Seq1 is a synthetic oligonucleotide which they used as a 18
test sequence,” and “[b]ecause this oligo was synthesized as a particular sequence, 19
there were multiple copies of the same fragment of DNA in the sample” 20
(Paper 250, p. 9). In other words, according to 454, the disclosure in these other 21
notebook pages establishes that 454 inventors conceived of (a) in Count 1. That 22
said, while it may be the case that certain pages in one notebook (Ex. 1093) 23
describe the binding of a particular synthetic DNA fragment to beads, page 16 in a 24
different notebook (Ex. 1094) does not sufficiently indicate that the inventors 25
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conceived of generating a plurality of a particular DNA fragment for use in a 1
method involving the aqueous microreactor depicted on page 16. 2
Page 16 itself in Exhibit 1094 specifically refers to beads (Sepharose-3
streptavidin HP beads), but does not mention any particular DNA fragment, such 4
as PRB1/Seq1. Instead, the page indicates that the human genome could be 5
amplified (see, e.g., Ex. 1094, bottom of p. 16), which is insufficient to describe (a) 6
of Count 1. In addition, the written comment on page 16 to “see sequencing 7
results” at pp. 52-59 in a different notebook (Ex. 1093) by itself fails to sufficiently 8
establish that the inventors conceived of (a) generating a plurality of a particular 9
DNA fragment (e.g., PRB1/Seq1 or otherwise) in relation to (b) delivering that 10
plurality of fragments into a plurality microreactors, such as the microreactor 11
depicted on page 16 of Exhibit 1093. 12
August–December 2002 13
Although 454 does not sufficiently establish conception in June 2002 based 14
on notebook page 16 alone (Ex. 1094), we next address whether 454 establishes 15
conception when working toward a reduction to practice after that time, but before 16
June 2003. 454 describes “[e]arly experiments to reduce the invention to practice,” 17
referring to experiments in August–December 2002 (Paper 250, pp. 11-13). 454 18
describes experimental difficulties during that time frame, such as microreactor 19
“crashing” (id. at 11). 454 also refers to inventor notebooks from December 2002 20
describing experiments using PCR products called “test fragments (‘TF’)” (id. at 21
12-13). 22
454 discusses experiments by inventor Dr. Leamon, and states that his 23
notebook 164 (Ex. 1097, pp. 7-9) shows an experiment dated December 31, 2002. 24
According to 454, this evidence depicts that Dr. Leamon “determined that they 25
needed to optimize the micelle formation to obtain more micelles with only a 26
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single bead inside. (Exhibit 1114, ¶30)” (Paper 250, p. 13). Along these lines, 1
page 7 of Dr. Leamon’s notebook (Ex. 1097), dated December 31, 2002, states that 2
“many micelles w/ multiple beads inside – need to optimize formulation process” 3
(Ex. 1097, bottom on p. 7). In addition, page 46 of the same notebook, dated 4
February 4, 2003, states: “looks good – many unoccupied droplets, but vast 5
majority of them w/ beads have only 1 bead/droplet” (id. at p. 46). Thus, 6
Dr. Leamon’s testimony and notebook pages indicate that he conceived of, and 7
ultimately reduced to practice, microreactors having only one bead per 8
microreactor as of February 2003. 9
We note, however, that 454 does not establish with this evidence alone that 10
the inventors conceived of making, or reduced to practice, a plurality of aqueous 11
microreactors comprising a particular DNA fragment, where each microreactor 12
contained one bead and one copy of the particular DNA fragment, as required in 13
(b) of Count 1.

454 further cites a paper by Sepp et al. (Ex. 1100) and a 14
declaration by Keith McDade (Ex. 1124), but such evidence does not sufficiently 15
address whether the inventors conceived or reduced to practice both (a) and (b) of 16
Count 1 during the August–December 2002 time frame (Paper 250, pp. 12-13). 17
Page 5 of Mr. McDade’s declaration (Ex. 1124), for example, states that “shortly 18
after the New Year in 2003,” inventors Dr. Sarkis and Dr. Leamon “did titration 19
experiments to determine the average number of copies per bead (cpb) that 20
provided optimal results.” 21
Experiments in January and February 2003 22
454 refers to experiments by inventors, and particularly Dr. Sarkis, in 23
January 2003 using an “F6” sequence and other “test fragments” as controls 24
(Paper 250, p. 14). To clarify, 454 may rely on the use of such controls to establish 25
that the inventors conceived of (a) of Count 1. Relevant experiments involving 26
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genomic libraries, such as an adenovirus library, by themselves do not present 1
methods involving (a) of Count 1. Inclusion of F6 and/or other test DNA 2
fragments as controls in such experiments, however, may correspond to (a) if one, 3
for example, generated F6 and/or other control test fragments by PCR, which 4
would have generated a plurality of the particular DNA fragment. 5
454 argues that page 118 of one of Dr. Sarkis’ notebook (Ex. 1105) 6
describes an experiment that “set up the final copy per bead as indicated in the 7
‘Finish’ column is 1 copy per bead (on average) per microreactor” (Paper 250, 8
p. 15, referring generally to pp. 113-122 of Ex. 1105). 454 also argues that 9
pages 123-141 of that notebook (Ex. 1105) disclose a reduction to practice on 10
January 28, 2003, including bead emulsion PCR using beads having “1 copy per 11
bead” of the F6 template (Paper 250, p. 16; see also Sarkis Declaration, Ex. 1115 12
¶¶ 27-29). In addition, 454 argues that pages 142-152 of the same notebook 13
disclose relevant experiments where an “Adeno library was used at 1 copy per 14
bead” or the experiments used “2 copies of genome fragment per bead” 15
(Paper 250, p. 16-18). 16
454 further refers to pages from a different notebook of Dr. Sarkis 17
(Ex. 1106) dated February 2003 (Paper 250, p. 18-24). 454 indicates that the 18
inventors performed emulsion PCR experiments on an adenovirus library, using 19
the F6 fragment as a control (see, e.g., id. at 18). 454 refers to experiments 20
involving the use of two copies of DNA fragments per bead (id. at 18-20, 29) or 21
0.5 copies per bead (id. at 30 (referring to “0.5 cpb”)). 454 also discusses 22
experiments described on pages 65-74 of Dr. Sarkis’ notebook (Ex. 1106) 23
involving “emulsion PCR runs using an average of 0.1 cpb, 0.5 cpb, 1 cpb and 2 24
cpb,” where “cpb” refers to copies of fragment DNA per bead (Paper 250, p. 22; 25
Ex. 1106, handwritten notes on p. 65, 71 (“1 copy/bd”). 454 states that “Dr. Sarkis 26
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can tell from these experiments that the template used in this experiment was an 1
adenovirus library, and that known, PCR-generated test fragments were included 2
as this was the standard practice at this point in time” (Paper 250, p. 22), citing 3
Dr. Sarkis’ notebook (Ex. 1106) and a declaration by Dr. Sarkis (Ex. 1115 ¶ 46). 4
454 further refers to laboratory notebook pages 79-87 and 106 of Dr. Sarkis’ 5
notebooks (Ex. 1106) as also describing experiments with “1 cpb,” i.e., one copy 6
of template fragment DNA per bead (Paper 250, p. 23). 7
Notwithstanding 454’s arguments, however, the cited passages of Dr. 8
Sarkis’ notebook (Exs. 1105 and 1106) and his declaration (Ex. 1115) do not by 9
themselves adequately show, and 454 does not sufficiently explain how this 10
evidence shows (Paper 250, pp. 13-24), experiments involving the making or using 11
microreactors where each microreactor contained only one template fragment 12
DNA and one bead. More specifically, even if Dr. Sarkis’ testimony and his 13
notebooks convey that the inventors prepared and used beads having only one 14
template fragment DNA, such as PCR generated F6, per bead (see, e.g., Ex. 1115 15
¶¶ 27-29, 46; Ex. 1105, pp. 118-143; Ex. 1106, pp. 65-74), 454 does not 16
adequately explain how such evidence describes two or more microreactors where 17
each microreactor contains only one template DNA (e.g., F6) and one bead. Thus, 18
454 arguments and cited notebook evidence relating to Dr. Sarkis’ work in 19
January-February 2003 by themselves (Paper 250, pp. 13-24) fail to adequately 20
establish and corroborate that 454 inventors conceived of and conducted relevant 21
experiments using two or more microreactors where each microreactor contained 22
only one template DNA (e.g., a PCR generated test fragment) and one bead, as 23
required in (b) of Count 1. 24
25
26
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February 2003 “Best Practices” document 1
Evidence sufficiently establishes that inventor Dr. Sarkis authored, and non-2
inventor Louis Ferland edited, the February 2003 “Best Practices” documents 3
(Exs. 1102, 1103, p. 1; Ex. 1118, pp. 4-5). The Best Practice document, entitled 4
“Emulsion Polymerase Chain Reaction (Emulsion PCR),” “describes the procedure 5
to amplify genomic template DNA from low (single effective) copy numbers” 6
(Ex. 1103, pp. 1-2). The document states that the “procedure comprises 6 main 7
steps: Template quality control; PCR solution preparation; Binding of the template 8
fragments to DNA Capture beads; Emulsion preparation; Amplification; and 9
Recovery of the DNA Template-carrying beads from the emulsion” (id. at 2). In 10
relation to the procedure, the document also refers to “capture beads” that “have, 11
on average, 1-2 copies of sstDNA bound to each bead, and are ready for Emulsion 12
PCR” (id. at 7). 13
454 acknowledges that the Best Practice document “was directed at doing 14
emulsion PCR to identify unknown sequences, in particular, to sequence entire 15
genomes from an organism” (Paper 250, p. 27). In other words, the document does 16
not disclose (a) of Count 1 because it does not describe generating two or more 17
copies of the same DNA fragment, for example by generating PCR test fragments 18
for use in the procedure. 454 argues, however, “the optimal conditions for 19
emulsion PCR had already been identified using known, PCR-generated, DNA 20
fragments such as F6” (Exhibit 1115 ¶ 38)” (id.). Paragraph 38 of Dr. Sarkis’ 21
declaration (Ex. 1115) simply notes that “Exhibit 1102 and 1103 show the 22
metadata of various changes Dr. Ferland and I made to the document,” and that 23
“the content of Exhibits 1102 and 1103 accurately reflects the information that was 24
present in the document, and which I conveyed to Dr. Ferland on February 12, 25
and February 13, 2003.” Similarly to 454’s priority motion, paragraph 41 of 26
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Dr. Sarkis’ declaration (Ex. 1115) also states that “as noted above, the optimal 1
conditions for emulsion PCR had already been identified using known, PCR-2
generated, DNA fragments such as F6.” Such arguments and paragraphs in 3
Dr. Sarkis’ declaration (Ex. 1115) are not sufficient to establish or corroborate 4
conception of (a) of Count 1 in relation to the Best Practice document alone, 5
however. 6
Moreover, while we see that the Best Practices document describes 7
delivering one DNA fragment per bead, 454 does not adequately establish that this 8
document by itself conveys that the inventors conceived of making a plurality of 9
aqueous microreactors comprising a particular DNA fragment, where each 10
microreactor contained one copy of the fragment and one bead, as required in 11
(b) of Count 1. 12
March 2003 Invention Disclosure Form 13
454 states that inventor “Dr. Sarkis inserted into his notebook an invention 14
disclosure that he submitted to Kent Lohman on February 23, 2003,” which 15
corresponds to an invention disclosure form hand-dated March 3, 2003 (Paper 250, 16
p. 28; Ex. 1106, pp. 107-112 (including “Feb. 26, 2003” handwritten at the top of 17
p. 107); Ex. 1131, p. 1 (including “3/3/03” handwritten in a “Date Stamp” 18
portion)). 454 points out that the invention disclosure form includes a copy of 19
page 16 of Dr. Berka’s notebook (Ex. 1131, p. 8; Ex. 1093, p. 16) and mentions the 20
February 2003 Best Practices document (Paper 250, p. 29; Ex. 1131, pp. 4-5). 21
Thus, the invention disclosure form discloses, or expressly references other 22
documents that disclose, (b) – (d) of Count 1. For example, because the form itself 23
includes pictures of microreactors containing only one bead per microreactor 24
(Ex. 1131, p. 5), as well as a copy of page 16 of Dr. Berka’s June 2002 depicting a 25
similar hand-drawn picture (id. at 8), the form provides evidence that the inventors 26
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15

conceived of using one bead per microreactor. As with page 16 of Dr. Berka’s 1
notebook and the Best Practice document, however, the invention disclosure form 2
by itself does not adequately disclose (a) of Count 1—it does not mention using 3
PCR generated test fragments as controls, for example. 4
March–May 2003 5
454 describes experiments conducted by 454 inventors in March–May 2003 6
(Paper 250, pp. 30-31). For example, 454 describes how inventors conducted 7
emulsion PCT in March 2003 on “adenovirus and TF6,” i.e., test fragment 6 8
(Ex. 1123 ¶ 12), at “1 cpb,” i.e., one copy of DNA fragment per bead (Paper 250, 9
p. 30; Ex. 1106, pp. 138-139). 454 also describes how inventors made “new test 10
fragments (new key) and emulsion PCR set-up using 2, 1, 0.5 and 0.1 copies per 11
bead” (Paper 250, p. 30-31; Ex. 1106, pp. 148-150). 12
Analysis 13
In its Opposition to 454’s priority motion, JHU argues that page 16 of 14
Dr. Berka’s notebook (Ex. 1094, p. 16), the Best Practice document (Exs. 1102, 15
1103) and the invention disclosure form (Ex. 1131) do not adequately establish that 16
the 454 inventors conceived of (a) in Count 1 (Paper 256, pp. 5-11, 14-19). We 17
agree for the reasons discussed above regarding these particular pieces of evidence 18
when considered alone. 19
JHU also argues that oral testimony by inventors in relation to “the idea of 20
using ‘cDNA libraries and PCR fragments’” in June 2002 is “undocumented” and 21
unreliable (id. at pp. 11-13). JHU further argues that the testimony of non-inventor 22
Mr. McDade (Ex. 1124) in this regard is hearsay and should be given no weight 23
(id. at pp. 13-14). We agree with regard to what 454 purports to establish 24
regarding conception in June 2002. As discussed above, the evidence does not 25
sufficiently establish or corroborate that the inventors conceived of (a) of Count 1 26
Interference No. 105,857
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in June 2002 in relation to the emulsion PCR procedure described on page 16 of 1
Dr. Berka’s notebook (Ex. 1094). 2
Our analysis does not end there, however. Other evidence relating to 3
activity by 454 inventors in January-February 2003, including testimony and 4
notebook evidence by both inventors and non-inventors, indicate that the inventors 5
conceive of using test fragment controls in relevant emulsion PCT experiments 6
otherwise described in Dr. Berka’s notebook (Ex. 1094, p. 16), the Best Practice 7
document (Exs. 1102, 1103), and the invention disclosure form (Ex. 1131). Thus, 8
such evidence indicates that the inventors conceived of (a) of Count 1 in relation to 9
a relevant emulsion PCR procedure, at least with regard to such controls. 10
JHU argues that the inventors’ “self-serving testimony is wholly lacking in 11
any details sufficient to substantiate the practice of the various steps of the Count 12
(particularly with respect to non-inventor witnesses, e.g., Tartaro (Ex 1117); Lanza 13
(Ex 1126); Ronan (Ex 1121); de Winter (Ex1123) and McDade (Ex 1124)” 14
(Paper 256, p. 20, see also id. at pp. 20-22). In addition, JHU argues that the 15
“referenced notebook records themselves lack sufficient detail to be self-16
explanatory” (id.). JHU further argues that evidence relating to “test fragments,” 17
such as F6, is unclear and/or inconclusive (id. at pp. 22-26). Along the same lines, 18
JHU maintains that experimental work by the 454 inventors is inconclusive (id. at 19
pp. 26-29). In addition, JHU argues that statistical arguments by 454 focus on the 20
ratio of templates per bead, rather than template per aqueous microreactor (id. at 21
29-31). JHU also offers additional arguments as to why 454 fails to establish that 22
its inventors conceived or reduced to practice (a) of Count 1, including that 454 23
inventors failed to appreciate using (a) when including PCR generated controls (id. 24
at 31-36). 25
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Certain aspects of JHU’s arguments regarding (a) of Count 1 have merit 1
when considering each different piece of evidence individually. The critical 2
question here, however, is whether evidence of record, when considered as a 3
whole, sufficiently shows and corroborates that the 454 inventors conceived of the 4
subject matter of Count 1 before June 2003. Price v. Symsek, 988 F.2d 1187, 1196 5
(Fed. Cir. 1993) (stating that “all of the evidence [] must be considered as a whole, 6
not individually, in determining whether [a party] conceived the invention of the 7
count before [another party]”). As explained in Price, “an inventor can 8
conceivably prove prior conception [] although no one piece of evidence in and of 9
itself establishes the prior conception.” Id. 10
In this case, 454 offers notebooks as evidence from inventors and non-11
inventors, as well as testimony by relevant witnesses describing what certain 12
notebooks pages depict. Moreover, 454 does not offer such notebooks and 13
testimony in isolation. For example, as discussed above, 454 provides the Best 14
Practice document (Exs. 1102, 1103) and the invention disclosure form (Ex. 1131). 15
Certain notebook pages expressly mention or include pages of the Best Practice 16
document (Ex. 1126 ¶ 15; Ex. 1125, p. 110), and the invention disclosure form 17
refers to the Best Practices document and attaches a copy of page 16 of Dr. Berka’s 18
notebook from June 2002 (Ex. 1093) (Ex. 1131; see also Ex. 1106, pp. 107-112). 19
Thus, even if certain inventor notebook pages are not abundantly detailed in what 20
they present in relation to every element of Count 1, other evidence provides 21
relevant information as to what the inventors conceived and hoped to reduce to 22
practice in such experiments. 23
Looking at all evidence of record collectively, we conclude that a 24
preponderance of the evidence shows and corroborates that 454 inventors 25
conceived of all elements of Count 1 before June 2003. For example, regarding 26
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(a) of Count 1, credible evidence exists from a number of non-inventors, such as 1
Dr. Lanza and others who supported Dr. Sarkis and the emulsion PCR project in 2
early 2003. Considered all together, such evidence sufficiently corroborates 3
Dr. Sarkis’ testimony that he conducted relevant experiments in January-February 4
2003 that included controls such F6 and/or other test fragments amplified by PCR. 5
(Sarkis Declaration, Ex. 1115 ¶¶ 27-29; Lanza Declaration, Ex. 1126 ¶ 11 (stating 6
that “I often used reagents made by others at 454, including libraries that Alex de 7
Winter made, and various test fragments designated as ‘TF” or “F_’, which we 8
used as controls to make sure our reactions were proceeding appropriately”); 9
Tartaro Declaration, Ex. 1117 ¶ 11 (stating same); de Winter Declaration, Ex. 1123 10
¶ 12 (stating that test fragments TF1, TF2, TF3, TF4, TF5, TF6, TF7, F6 and N7 11
“were PCR-generated fragments that we would often use as controls to optimize 12
various aspects of our protocols”); Altman Declaration, Ex. 1120 ¶¶ 7-10 (stating 13
that “[w]hen we needed F6 fragment for an experiment, it would be amplified by 14
PCR from the plasmid and put into control beads for testing sequencing”).)
2
Such 15
evidence sufficiently establishes and corroborates that 454 inventors conceived of 16
generating a plurality of particular DNA fragments by PCR, i.e., test fragments, 17
and using such test fragments as controls in relevant PCR emulsion experiments as 18
of February 2003. 19
Moreover, as long as the inventors conceived of performing (a), i.e., 20
generating a plurality of molecules of a particular fragment of DNA, along with 21

2
We note that Dr. Leamon states that the “F6 template was an adenovirus cDNA
library which was generated by GJS (Gary J. Sarkis) and MR (Michael Ronan)”
(Ex. 1114 ¶ 32). Dr. Sarkis and Mr. Ronan (and other witnesses) consistently
testify, however, that F6 was a particular PCR amplified template DNA fragment
used as a control in relevant experiments (see. e.g., Ex. 1115 ¶¶ 26-27; Ex. 1121
¶ 15). A preponderance of the evidence establishes that F6 and other test
fragments were generated by PCR and used in PCR experiments by 454 inventors.
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(b) – (d) of Count 1, it does not matter whether the inventors failed “to appreciate 1
the value of step (a)” beyond its use to generate a control used in the method 2
(Paper 256, pp. 34-35). Evidence establishes that the inventors appreciated that 3
(a) took place, regardless of its “value” in relation to benefits of the protocol in 4
amplifying genomic template DNA. 5
Regarding (b) of Count 1, 454 offers evidence corroborating Dr. Sarkis’ use 6
of one template fragment DNA per bead in a relevant method. Dr. Lanza, a non-7
inventor, testifies that she “was well aware of the successful emulsion PCR 8
experiments by Gary Sarkis, including the sequencing he did with F6 and 9
adenovirus libraries, and using various ratios of template to bead, including one 10
template per bead” (Ex. 1126 ¶¶ 14, 11). Dr. Tartaro, another non-inventor who 11
also provided support to Dr. Sarkis in early 2003, testifies similarly (Tartaro 12
Declaration, Ex. 1117 ¶ 11, 17-22). 13
In addition, as discussed above, page 16 of Dr. Berka’s notebook dated 14
June 2002 (Ex. 1094) and his testimony (Ex. 1113 ¶ 19), as well as pages from 15
Dr. Leamon’s notebook from December 2002 and February 2003 (Ex. 1097, pp. 7, 16
46), provide evidence that 454 inventors conceived of relevant microreactors 17
having one bead per microreactor, another aspect of (b) of Count 1. Regarding this 18
evidence, Dr. Sarkis testifies that he recalls page 16 of Dr. Berka’s notebook as 19
“being one of the first written documents describing our idea” (Ex. 1115 ¶ 17). 20
Along these lines, Dr. Sarkis states that on this same notebook page, Dr. Berka 21
“made reference to an article I had found, Katsura et al. (Exhibit 1098)” (id.). 22
Mr. Srinivasan had a similar understanding and witnessed the notebook page on 23
the same day it was generated by Dr. Berka in June 2002 (Ex. 1116 ¶ 9) (stating 24
that he “recall[s] this being one of the first written documents describing this 25
idea”). 26
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Furthermore, the invention disclosure form of February-March 2003, which 1
is reproduced in Dr. Sarkis’ notebook pages, attaches a copy of page 16 of 2
Dr. Berka’s notebook including a handwritten drawing of a microreactor 3
containing one bead (Ex. 1131, p. 8; Ex. 1106, pp. 107-112; Ex. 1115 ¶ 48). The 4
invention disclosure form itself includes more formal pictures of microreactors 5
containing only one bead per microreactor in a section that also mentions the 6
February 2003 Best Practices document (Ex. 1131, p. 5, under “Detailed 7
Description of Invention”). 8
We note that 454 inventors produced, in some capacity at different times, the 9
above-mentioned evidence relating to conception of microreactors having only one 10
bead per microreactor. “[A]n inventor’s testimony, standing alone, is insufficient 11
to prove conception—some form of corroboration must be shown.” Price, 988 12
F.2d at 1194; In re Garner, 508 F.3d 1376, 1380 (Fed. Cir. 2007). That said, we 13
apply a “rule of reason” analysis to determine whether an inventor’s prior 14
conception testimony has been corroborated. Price, 988 F.2d at 1195. Moreover, 15
oral testimony by inventors is not the only relevant evidence of record here. “An 16
evaluation of all pertinent evidence must be made so that a sound determination of 17
the credibility of the inventor’s story may be reached.” Id. (emphasis added). 18
“Documentary or physical evidence that is made contemporaneously with the 19
inventive process provides the most reliable proof that the inventor’s testimony has 20
been corroborated.” Sandt Technology, Ltd. v. Resco Metal and Plastics Corp., 21
264 F.3d 1344, 1350-51 (Fed. Cir. 2001). Corroboration is not necessary to 22
establish what a physical exhibit discloses. Price, 988 F.2d at 1195. 23
In addition, we note that corroboration of a conception involves a less 24
stringent standard than that needed to corroborate a reduction to practice. Singh v. 25
Brake, 222 F.3d 1362, 1369-70 (Fed. Cir. 2000) (stating that “to corroborate a 26
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reduction to practice, [we apply] a more stringent standard than that required to 1
corroborate a conception”); see also Mikus v. Wachtel, 542 F.2d 1157, 1161 2
(CCPA 1976) (holding that an invention record, based on an unwitnessed 3
laboratory notebook and results performed by technicians unaware of what they 4
were testing, may provide sufficient evidence of conception but not reduction to 5
practice under the rule of reason). 6
Here, the Best Practices document edited by non-inventor Mr. Ferland (in 7
relation to (b) – (d) in Count 1) in combination with testimony and laboratory 8
notebooks of a number of non-inventors (in relation to (a) – (d) of Count 1) 9
adequately corroborates conception by 454 inventors of nearly every element of 10
Count 1, as discussed above. Regarding one aspect in (b) of Count 1 relating to 11
microreactors having only one bead per microreactor (and therefore only one DNA 12
fragment per microreactor), relevant evidence includes testimony from multiple 13
inventors, documentary/physical evidence in the form of laboratory notebooks and 14
an invention disclosure form generated and witnessed/corroborated by different 15
inventors before June 2003, as well as the Best Practices document. 16
We mention the Best Practices document of February 2003, which is 17
corroborated by non-inventors including Mr. Ferland, because it states that 18
“[d]elivery of excess [template DNA fragment] species can result in amplification 19
of a mixed template population, preventing generation of meaningful sequencing 20
data” (Ex. 1103, p. 6). The Best Practices document also states that “[i]f the 21
emulsion is broken, it is likely that many [] beads will have a mixture of templates” 22
which may require one to “start over” (id. at p. 9). 23
Such statements are consistent with the goal of producing microreactors 24
containing only one template DNA per microreactor (and one bead per 25
microreactor), exactly as described by 454 inventors in their testimony and 26
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disclosed in the above-mentioned documents generated by inventors in early 2003. 1
If microreactors contained more than one template DNA per microreactor, the 2
emulsion PCR would run into the same problem of “amplification of a mixed 3
template population” discussed in the Best Practices document (id. at pp. 6, 9) 4
In quick summary, at least the Best Practices document (corroborated by 5
non-inventors) and the invention disclosure form (corroborated by inventors) 6
expressly discloses (c) and (d) of Count 1 in a relevant PCR emulsion procedure. 7
Regarding (a) and (b) of Count 1: 8
454 Evidence
(individually)
Adequately establishes
conception of:
Does not adequately
establish conception of:
Page 16 of Dr. Berka’s
notebook (Ex. 1094)
(b) (a)
Evidence regarding Aug.-
Dec. 2002 experiments
(a) and part of (b) (b) regarding one DNA
fragment per bead per
microreactor
Evidence regarding Jan.-
Feb. 2003 experiments
(a) and part of (b) (b) regarding one DNA
fragment per bead per
microreactor
“Best Practices”
document (Feb. 2003)
(Ex. 1102/1103)
Part of (b) (a) and (b) regarding one
DNA fragment per bead
per microreactor
Invention Disclosure
Form (Mar. 2003)
(b) (a)
9
Under a rule of reason analysis, we find the above-mentioned evidence, as a 10
whole, to be credible to establish that the 454 inventors conceived the subject 11
matter of Count 1, including delivering a plurality of DNA fragments, i.e., test 12
fragments, such as F6, used as controls, as encompassed by (a) in Count 1, into 13
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aqueous microreactors, where each microreactor comprises one DNA test fragment 1
and one single bead, as required in (b) of Count 1. 2
Thus, Senior Party 454 establishes by a preponderance of the evidence that it 3
conceived of the subject matter of Count 1 before June 5, 2003, i.e., before JHU’s 4
date of conception as discussed above. Both parties establish a reduction to 5
practice based on a constructive reduction to practice. Thus, 454 establishes an 6
earlier reduction to practice as of its June 6, 2003 filing date, as compared to JHU’s 7
filing date of July 5, 2003. Because 454 has shown both an earlier conception and 8
an earlier reduction to practice, its diligence is moot. 35 U.S.C. §102(g). 9
V. CONCLUSION 10
For the reasons discussed above, we deny JHU’s motion for priority and 11
grant 454’s motion for priority. 454 establishes by a preponderance of the 12
evidence that it is entitled to priority regarding Count 1. 13
VI. ORDER 14
It is 15
ORDERED that JHU Motion 3 (Paper 241) for judgment based on priority 16
is denied; 17
FURTHER ORDERED that 454 Motion 3 (Paper 250) for judgment based 18
on priority is granted; and 19
FURTHER ORDERED that a copy of this Decision be placed in each of 20
the files of (1) JHU application 12/361,690, and (2) 454 application 13/033,240. 21
22
23
24
Interference No. 105,857
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cc (e-mail):

For JHU:

Sarah A. Kagan, Esq.
Joseph M. Skerpon, Esq.
Banner & Witcoff, Ltd.
1100 13th Street, N.W., Suite 1200
Washington, DC 20005
E-mail: skagan@bannerwitcoff.com
E-mail: jskerpon@bannerwitcoff.com

Charles W. Calkins, Esq.
Cynthia B. Rothschild, Esq.
Kilpatrick Townsend & Stockton LLP
1001 West Fourth Street
Winston-Salem, NC 27101
E-mail: ccalkins@kilpatricktownsend.com
E-mail: crothschild@kilpatricktownsend.com

For 454:

R. Danny Huntington, Esq.
Sharon E. Crane, Ph.D., Esq.
Rothwell, Figg, Ernst & Manbeck, P.C.
607 14th St., N.W., Suite 800
Washington, DC 20005
E-mail: dhuntington@rfem.com
E-mail: scrane@rfem.com

Ivor R. Elrifi, Ph.D., Esq.
Mintz, Levin, Cohn, Ferris, Glovsky & Popeo, P.C.
One Financial Center
Boston, MA 02111
E-mail: IRElrifi@mintz.com