Bioactive Laboratoriesv.BTG International Inc.

Patent Trial and Appeal Board

Dec 10, 2015

08405454 (P.T.A.B. Dec. 10, 2015)

Trials@uspto.gov Paper 19
571-272-7822 Entered: December 10, 2015

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

BIOACTIVE LABORATORIES,
Petitioner,

v.

BTG INTERNATIONAL INC.,
Patent Owner.

Case IPR2015-01305
Patent 8,048,414 B

Before TONI R. SCHEINER, LORA M. GREEN, and
SHERIDAN K. SNEDDEN, Administrative Patent Judges.

SCHEINER, Administrative Patent Judge.

DECISION
Denying Institution of Inter Partes Review
37 C.F.R. § 42.108

IPR2015-01305
Patent 8,048,414 B1

2

I. INTRODUCTION
Bioactive Laboratories (“Petitioner”) filed a Petition (Paper 2, “Pet.”)
on May 29, 2015, requesting an inter partes review of claims 1–22 of
U.S. Patent No. 8,048,414 B1 (Ex. 1001, “the ’414 patent”). BTG
International Inc. (“Patent Owner”) filed a Preliminary Response (Paper 12,
“Prelim. Resp.”) on September 11, 2015.1 We have jurisdiction under
35 U.S.C. § 314, which provides that an inter partes review may not be
instituted “unless . . . there is a reasonable likelihood that the petitioner
would prevail with respect to at least 1 of the claims challenged in the
petition.”
Upon consideration of the information presented in the Petition and
the Preliminary Response, we are not persuaded that Petitioner has
established a reasonable likelihood that it would prevail in its challenges to
claims 1–22 of the ’414 patent. Accordingly, we decline to institute an inter
partes review of those claims.
A. Related Proceedings
Petitioner represents that the ’414 patent was involved in a prior inter
partes review which was terminated prior to a decision on institution:
Laboratorios Silances, S.A. de C.V. v. BTG Int’l Inc., Case IPR2014-01269
(PTAB). In addition, Petitioner represents that the ’414 patent was involved

1 Patent Owner filed a Motion to Seal its Preliminary Response, as well as
Exhibit 2033, submitted in support of the Preliminary Response. Paper 14.
Patent Owner filed also a redacted version of the Preliminary Response.
Paper 13.
IPR2015-01305
Patent 8,048,414 B1

3

in an investigation before the U.S. International Trade Commission: Certain
Antivenom Compositions and Products Containing the Same (Inv. No. 337-
TA-903). Petitioner was not a party to either matter. Pet. 1.
Patent Owner represents it is not aware of any other judicial or
administrative matters that would affect, or be affected by, a decision in the
proceeding. Paper 4.
B. The Asserted Grounds of Unpatentability
Petitioner asserts the challenged claims are unpatentable on the
following grounds. Pet. 12–60.2
References Basis Claims Challenged
the ’352 patent3 § 102 1–7, 9–18, 21, and 22
the ’352 patent and the
WHO Report4 § 103 8 and 19

2 Petitioner supports its challenge with the Declaration of Anthony
Kossiakoff, Ph.D., executed May 27, 2015, (“the Kossiakoff Declaration”)
(Ex. 1002), and the Declaration of Richard F. Clark, Jr., M.D., executed May
25, 2015 (“the Clark Declaration”) (Ex. 1024).
3 U.S. Patent No. 4,849,352, issued July 18, 1989 to Sullivan et al. (“the
’352 patent”) (Ex. 1004).
4 WORLD HEALTH ORG., WHO OFFSET PUBLICATION NO. 58, 3–44,
PROGRESS IN THE CHARACTERIZATION AND STANDARDIZATION OF
ANTIVENOMS (1981) (“the WHO Report”) (Ex. 1006).
IPR2015-01305
Patent 8,048,414 B1

4

References Basis Claims Challenged
Chang5 and the WHO
Report § 103 1–7, 9–18, and 20–22
Chang, the WHO Report,
and Smith6 § 103 8 and 19
C. The ’414 Patent (Ex. 1001)
The ’414 patent, titled “Antivenom Composition Containing Fab[7]
Fragments,” discloses “enzymoabsorbed affinity methods combined with
reversible immunoabsorption chromatography procedures to produce and
isolate F(ab) and F(ab)2 fragments . . . to snake venoms as well as other
venoms.” Ex. 1001, 3:22–27. In addition, the ’414 patent discloses an
immunoabsorption procedure which produces “a highly refined IgG
antibody from a bulk antibody source.” Id. at 3:28–30.
According to the ’414 patent, “[t]he F(ab) fragments, F(ab)2
fragments and IgG thus produced are more highly purified, have greater
antibody activities and are less likely to produce immunogenic reactions

5 C.C. Chang & C.C. Yang, Immunochemical Studies on Cobrotoxin,
102 J. IMMUNOL. 1437–44 (1969) (“Chang”) (Ex. 1005).
6 T.W. Smith et al, Immunogenicity and kinetics of distribution and
elimination of sheep digoxin-specific IgG and Fab fragments in the rabbit
and baboon, 36 CLIN. EXP. IMMUNOL. 384–96 (1979) (“Smith”) (Ex. 1007).
7 The acronym “Fab” (which stands for “fragment antigen-binding”) is used
interchangeably with “F(ab)” in the ’414 patent, the briefings, and this
decision.

IPR2015-01305
Patent 8,048,414 B1

5

than their counterpart antibodies produced by processes utilizing [prior art]
precipitation procedures.” Id. at 3:32–37. Further according to the ’414
patent, “lethality-neutralizing . . . tests clearly established that the F(ab)
fragment antibodies and IgG produced by the processes of this invention
afford better protection against venom-induced pathophysiology than the
[prior art] commercial antivenin on a milligram per milligram basis.” Id. at
4:43–48. In addition, the ’414 patent teaches that F(ab)2 fragments
produced according to the invention “should also afford greater protection
against venom-induced pathophysiology than the commercial antivenin . . .
[and] produce less acute hypersensitivity reactions than those produced by
the commercial antivenin.” Id. at 4:54–58.
Finally, the ’414 patent teaches that “IgG, F(ab) fragments and F(ab)2
fragments often have separate utilities” and “F(ab) and F(ab)2 fragments
may sometimes be used together.” Id. at 2:1–3. According to the ’414
patent, Fab fragments and F(ab)2 fragments will have the same antibody
specificity as the antibody they are cleaved from, but their differing
molecular weights affect a number of functions, including distribution in the
body (e.g., whether or not they can cross the blood/brain barrier), the ability
to be excreted by kidney functions, etc. Id. at 1:42–2:50.
If, for example a sought after antigen molecule is already a
large molecule, the use of F(ab) fragments is limited. Even
though the F(ab) fragments can be used to neutralize large
antigen molecules, the kidneys still will not be able to excrete
them. In such cases it may be better to use a whole IgG
IPR2015-01305
Patent 8,048,414 B1

6

molecule to find the large antigen molecule so that the entire
molecule assembly is phagocytized.
Id. at 2:18–24.
D. Illustrative Claims
Petitioner challenges claims 1–22 of the ’907 patent. Claims 1, 19,
and 20 are independent. Claims 1 and 20, reproduced below, are illustrative.
1. An antivenom pharmaceutical composition for treating a
snakebite victim, comprising Fab fragments which bind
specifically to a venom of a snake of the Crotalus genus and
which are essentially free from contaminating Fc as determined
by immunoelectrophoresis using anti-Fc antibodies, and a
pharmaceutically acceptable carrier, wherein said antivenom
pharmaceutical composition neutralizes the lethality of the
venom of a snake of the Crotalus genus.
20. An antivenom pharmaceutical composition for treating a
snakebite victim, comprising Fab fragments which bind
specifically to a venom of a snake of the Crotalus genus and
which are essentially free from contaminating Fc as determined
by immunoelectrophoresis using anti-Fc antibodies, and a
pharmaceutically acceptable carrier, wherein said Fab
fragments neutralize the lethality of the venom of a snake of the
Crotalus genus in the absence of IgG and F(ab)2.
Ex. 1001, 13:16–23, 14:35–42.
II. ANALYSIS
A. Claim Construction
In an inter partes review, claim terms in an unexpired patent are
interpreted according to their broadest reasonable construction in light of the
specification of the patent in which they appear. 37 C.F.R. § 42.100(b);
IPR2015-01305
Patent 8,048,414 B1

7

Office Patent Trial Practice Guide, 77 Fed. Reg. 48,756, 48,766 (Aug. 14,
2012); In re Cuozzo Speed Techs., LLC, 793 F.3d 1268, 1275–79 (Fed. Cir.
2015). Under that standard, claim terms are given their ordinary and
customary meaning, as would be understood by one of ordinary skill in the
art in the context of the entire disclosure. In re Translogic Tech., Inc., 504
F.3d 1249, 1257 (Fed. Cir. 2007).
Petitioner and Patent Owner proffer proposed constructions of several
claim terms (Pet. 11–18; Prelim. Resp. 17–22), but we determine that none
of these claims terms requires construction beyond our discussion below of
the claim term “said [or the] antivenom pharmaceutical composition
neutralizes the lethality of the venom of the snake of the Crotalus genus.”
B. Claims 1–7, 9–18, 21, and 22—Asserted Anticipation
by the ’352 Patent
1. The ’352 Patent (Ex. 1004)
The ’352 patent, titled “Antibody Purification Process,” matured from
application No. 06/659,629 (“the ’629 application”), and was filed on
October 9, 1984.
The ’414 patent was filed on March 15, 1995, as a
Continuation of application No. 08/277,288, filed on Jul. 22,
1994, now abandoned, which is a continuation of application
No. 08/124,438, filed on Sep. 22, 1993, now abandoned, which
is a continuation of application No. 07/5 93,271, filed on Oct. 1,
1990, now abandoned, which is a division of application No.
07/ 378,925, filed on Jul. 12, 1989, now abandoned, which is a
division of application No. 06/659,629, filed on Oct. 9, 1984,
now Pat. No. 4,849,352.
IPR2015-01305
Patent 8,048,414 B1

8

Ex. 1001, [22], [60].
Petitioner and Patent Owner agree that the disclosures of the ’352
patent and the ’414 patent are identical. Ex. 1001; Ex. 1004; Pet. 29; Prelim.
Resp. 23.
2. Analysis
Petitioner contends that claims 1–7, 9–18, 21, and 22 of the ’414
patent “are not entitled to the benefit of any earlier-filed application
identified in the [’414] patent’s priority claim” (Pet. 20), because no earlier-
filed application “discloses and enables the invention claimed in the later
filed application sufficient to satisfy the requirements of § 112” with respect
to these claims (id.). Accordingly, Petitioner contends that the ’352 patent,
which was filed on October 9, 1984, and issued on July 18, 1989, “is prior
art to the ’414 patent under 35 U.S.C. § 102(b).” Id. at 29.
Claim 1 is directed, in relevant part, to an antivenom pharmaceutical
composition comprising Fab fragments which bind specifically to a venom
of a snake of the Crotalus genus, wherein “said antivenom pharmaceutical
composition neutralizes the lethality of the venom of a snake of the Crotalus
genus” (the “neutralizes the lethality” limitation).
Petitioner acknowledges that “technological knowledge describe[s]
antivenom compositions comprising antibody fragments that are the active
components.” Id. at 22. Petitioner, however, contends that the challenged
claims “are broader than the supporting disclosure because they encompass
an antivenom pharmaceutical composition containing Fab fragments that do
IPR2015-01305
Patent 8,048,414 B1

9

not necessarily have to neutralize the lethality of the venom” (id.), thus, the
claims “encompass nearly unlimited compositions that are defined almost
exclusively by their function” (id.). Petitioner contends that “[n]one of the
priority applications describe[s] any components other than antibodies or
antibody fragments that could function to neutralize the lethality of the
venom of a Crotalus snake.” Id. (citing Ex. 1002 ¶ 53). Petitioner contends,
therefore, that the claims “lack written description support in the alleged
priority applications, because those applications do not adequately describe
what the claimed compositions are.” Id.
Additionally, Petitioner contends that “none of the priority
applications enable the full scope of the claims” (id. at 24 (citing Ex. 1002
¶¶ 53–55)), because “direction . . . for making and using Fab fragment-based
antivenom pharmaceutical compositions where the Fab fragments do not,
themselves, neutralize lethality” is lacking in the priority applications and in
the prior art (id. at 24–25 (citing Ex. 1002 ¶¶ 56–58)).
Petitioner’s broad construction of the “neutralizes the lethality”
limitation to include compositions in which Fab fragments or a combination
of Fab and F(ab)2 fragments do not neutralize the lethality of Crotalus
venom, forms the basis of its contention that the ’352 patent “is prior art to
the ’414 patent under 35 U.S.C. § 102(b), given the March 15, 1995
effective filing date of claims [1–7, 9–18], 21, and 22.” Id. at 29. Petitioner
contends that “the ’352 patent specification—which is identical to the ’414
patent specification—[nevertheless] does disclose at least one specific or
IPR2015-01305
Patent 8,048,414 B1

10

subgeneric embodiment that anticipates each and every element of the
broadly construed claims 1–7, 9–18, 21, and 22.” Id. at 29.
As discussed above, however, in an inter partes review, claim terms
in an unexpired patent are interpreted according to their broadest reasonable
construction in light of the specification of the patent in which they appear.
The specification of the ’352 patent (which matured from the ’629
application), like the specification of the ’414 patent, discloses that
“lethality-neutralizing . . . tests clearly established that the F(ab) fragment
antibodies and IgG produced by the processes of this invention afford . . .
protection against venom-induced pathophysiology” (Ex. 1004, 4:53–57),
and that “F(ab)2 fragments [produced according to the invention] should also
afford . . . protection against venom-induced pathophysiology” (id. at 4:66–
67). In addition, the specification of the ’352 patent, like the specification of
the ’414 patent, discloses that “IgG, F(ab) fragments and F(ab)2 fragments
often have separate utilities” and “F(ab) and F(ab)2 fragments may
sometimes be used together.” Id. at 1:61–63.
We are not persuaded that Petitioner has shown that the ’629 priority
application (or the ’352 patent) fails to provide proper written descriptive
support or enablement for claim 1. In a nutshell, we agree with Patent
Owner that “construing the limitation to include compositions in which the
Fab or Fab/F(ab)2 fragments do not neutralize the lethality of Crotalus
venom is not reasonable in light of the specification.” Prelim. Resp. 25.
That is, we agree that “[p]roperly construed, the claims cover a composition
IPR2015-01305
Patent 8,048,414 B1

11

in which Fab fragments neutralize venom, either alone or in combination
with F(ab)2 fragments.” Id.
Moreover, to the extent Petitioner argues that the general statement in
the background section of the specification of the ’352 patent that “Fab and
F(ab)2 fragments may sometimes be used together” (Ex. 1004, 1:62–63) is
inadequate to describe or enable compositions containing both Fab and
F(ab)2 fragments wherein the composition neutralizes the lethality of the
venom of a snake of the Crotalus genus (Pet. 25–26 (citing Ex. 1002 ¶¶ 59–
61)), we are not persuaded. We note that the Examiner considered this very
issue during prosecution of the ’414 patent. That is, the Examiner
acknowledged that “[t]he specification sets forth the concept of antivenoms
comprised of Fabs and F(ab)2” (Ex. 1016, 1209), but was concerned initially
that the specification “does not provide any description of how such
components would be effective . . . [because] Fabs and F(ab)2s would be
expected to compete for binding to the same sites and could thus reasonably
be expected to interfere with each other’s activity” (id. at 1209–10). As
explained in the Examiner’s Answer, following a series of interviews, and
consideration of several declarations of record, the Examiner concluded
“based on the evidence of record, that this competition would likely be
minimized because of the differences in the various antibody fragment
pharmacokinetics.” See id. at 1538.
In summary, we are not persuaded that Petitioner has shown that the
’352 patent is prior art to claim 1 of the ’414 patent. Moreover, we are not
IPR2015-01305
Patent 8,048,414 B1

12

persuaded that Petitioner has shown that the ’629 application (or the ’352
patent) fails to provide written description support and enablement for the
additional limitations of claims 2–7, 9–18, 21, and 22. Therefore, we are not
persuaded that Petitioner has demonstrated a reasonable likelihood of
prevailing in its challenge to claims 1–7, 9–18, 21, and 22 on the basis of
anticipation by the ’352 patent.
C. Claims 8 and 19—Asserted Obviousness over the
’352 Patent and the WHO Report
Claim 8 is directed to “[t]he antivenom pharmaceutical composition
of claim 1, further comprising F(ab)2 fragments.” Claim 19 is an
independent claim—like claim 8, claim 19 is directed to an antivenom
pharmaceutical composition that comprises both Fab and F(ab)2 fragments,
“wherein the antivenom pharmaceutical composition neutralizes the lethality
of the venom of a snake of the Crotalus genus.”
For the reasons discussed above, we are not persuaded that the ’352
patent lacks written description support and enablement for an antivenom
pharmaceutical composition comprising Fab fragments and F(ab)2 fragments
“wherein said antivenom pharmaceutical composition neutralizes the
lethality of the venom of a snake of the Crotalus genus.” Thus, this
challenge, based on the ’352 patent, suffers from the same infirmity as that
discussed above, in that Petitioner has not established that the ’629 priority
application fails to provide proper written descriptive support or enablement
for claims 8 and 19.
IPR2015-01305
Patent 8,048,414 B1

13

Therefore, we are not persuaded that Petitioner has shown that the
’352 patent is prior art to claims 8 and 19. Consequently, we are not
persuaded that Petitioner has demonstrated a reasonable likelihood of
prevailing in its challenge to claims 8 and 19 on the basis of obviousness
over the ’352 patent and the WHO Report.
D. Claims 1–7, 9–18, and 20–22—Asserted Obviousness
over Chang and the WHO Report
1. Chang (1005)
Chang describes a study conducted in 1968 in which the crystalline
toxic protein, cobrotoxin, isolated from Formosan cobra venom, was used as
an antigen to produce antiserum. Ex. 1005, 1. “The immunologic activities
of the antisera and of the specific antibody purified were investigated” (id.),
as was the activity of “univalent [Fab] fragments” obtained by papain
digestion of the purified antibody (id.). The results indicated that
“cobrotoxin is immunochemically homogeneous and is the main toxic
protein in Formosan cobra venom.” Id. at 7. The univalent Fab fragments
were used to determine that cobrotoxin has three antibody combining sites
per molecule. Id.
In addition, the neutralizing capacity of the various antibody
preparations was tested by pre-incubating the antibody preparations with
cobra venom and cobrotoxin, removing precipitates, and injecting the
supernatants intraperitoneally into mice. Id. at 2, 3, Table II. “The specific
neutralizing capacity of F I [the fraction containing Fab fragments] was even
IPR2015-01305
Patent 8,048,414 B1

14

higher than that of the purified antibody” (id. at 4, Table II (compare
purified antibody with papain digest FI)), and “[t]he neutralizing capacity of
all antibody preparations was of the same order for both cobra venom and
cobrotoxin, indicating that cobrotoxin is the main toxic protein in cobra
venom” (id. at 3).
According to Chang, “[t]he univalent [Fab] fragments together with
the purified antibody may provide valuable tools for an immunochemical
approach to the elucidation of the toxic nature of snake venom.” Ex. 1005,
7. Further according to Chang, “[s]ince the neutralizing capacity of the
purified antibody was 17.5 times greater than that of the antisera, . . . this
may also contribute to the therapy of snake bites.” Id.
2. The WHO Report (Ex. 1006)
The WHO Report, titled “Progress in the Characterization of Venoms
and Standardization of Antivenoms,” was published in 1981, and includes a
“Table of Poisonous Animals and Available Antivenoms” (Ex. 1006, 1, 26–
36) that lists several antivenoms effective against various species of
Crotalus (id. at 26).
The WHO Report notes that “[a] survey of the immunochemical
purity of commercially available antivenoms has disclosed a wide variety of
composition” (Ex. 1006, 15), and that “[o]nly a few are nearly pure F(ab)2
immunoglobulins and some are even crude unpurified hyperimmune horse
serum.” Id. Petitioner does not point to, and we do not find, any mention of
antivenoms containing Fab fragments. Moreover, the WHO Report states
IPR2015-01305
Patent 8,048,414 B1

15

that “proposed international standard antivenoms,” including one effective
against Crotalus adamanteus, “should be an almost pure F(ab)2 plasma
fraction.” Ex. 1006, 37.
2. Analysis
With respect to claim 1, Petitioner, relying on Dr. Kossiakoff’s
testimony, contends that:
[A person of ordinary skill in the art] would have had a reason
to combine the teachings of Chang and the WHO report to
arrive at the subject matter recited by independent claims 1 and
20, and . . . would have had a reasonable expectation of success
in doing so. Chang teaches an antivenom composition
comprising Fab fragments that bind cobrotoxin and are capable
of neutralizing both cobrotoxin and cobra venom, and the WHO
report discloses Crotalus genus antivenoms. Ex. 1002, ¶83. A
[person of ordinary skill in the art] would have been motivated
to combine the teachings of the two references to generate an
antivenom having the in vivo activity of the Fab fragment-
containing antivenoms (as in Chang), applied to Crotalus (as in
WHO), which would not cause serum sickness to take
advantage of Fab fragment in vivo characteristics. See Ex.
1002, ¶¶95-96. The resulting antivenom composition would
comprise Fab fragments (as in Chang) against Crotalus snake
venom (as in WHO). Id. Because of Chang’s effectiveness in
neutralizing cobra snake venom, a [person of ordinary skill in
the art] would have had a reasonable expectation of success
because the [person of skill in the art] would only be applying
the teachings to a different species of snake. Crotalus venom
would also have . . . reasonably been expected to behave
similarly to cobra venom in vivo.
Pet. 39–40.
IPR2015-01305
Patent 8,048,414 B1

16

As Dr. Kossiakoff explains, “the WHO report discloses that whole
antibody based antivenom . . . [against Crotalidae] causes unwanted immune
reactions” and “[a]s of October 9, 1984, Fab fragments were known to be
less prone to have immune reactions than whole antibody antivenoms.” Ex.
1002 ¶ 96. “As such, a [person of ordinary skill in the art] reading Chang
would also have had a reason to extend Chang’s Fab fragments to fragments
against Crotalus venom because Fab fragments would cause less unwanted
immune reaction.” Id.
In addition, with respect to independent claim 20, which requires that
the Fab fragments neutralize the lethality of Crotalus venom in the absence
of IgG and F(ab)2, Petitioner contends that one of ordinary skill in the art,
“would have had a reason to keep the advantages of Fab fragments by
including a sufficient quantity of the Fab fragments such that they neutralize
the lethality of Crotalus venom, regardless whether IgG or F(ab)2 fragments
are present.” Id. at 44.
Patent Owner contends, at least in part, that “Chang teaches that
antibody [Fab] fragments can be useful as a research tool for studies on
cobrotoxin” (Prelim. Resp. 32), but “the only statement in Chang that
suggests a potential therapeutic application focuses on whole [purified]
antibodies” (id. at 33).
We agree with Patent Owner on this point—Chang explicitly
characterizes both the Fab fragments and the purified antibody as “valuable
tools for an immunochemical approach to the elucidation of the toxic nature
IPR2015-01305
Patent 8,048,414 B1

17

of snake venom” (Ex. 1005, 7), but only the purified antibody is mentioned
in connection with “the therapy of snake bites” (id.), despite Chang’s
observation that “[t]he specific neutralizing capacity of F I [the fraction
containing Fab fragments] was even higher than that of the purified
antibody” (id. at 4, Table II).
Moreover, Patent Owner contends that Petitioner’s argument “is based
on the assumption that [a person of ordinary skill in the art] would have
believed that experimental results obtained using cobrotoxin, the single
dominant toxin of the [Formosan] cobra venom, could easily be extrapolated
to complex venoms such as venom of the Crotalus genus.” Prelim. Resp.
35–36.
Patent Owner contends that it is not the case that one of ordinary skill
in the art would have “extrapolat[ed] the teachings of Chang to such
venoms.” Id. at 36.
[C]obrotoxins, as disclosed in Chang, are relatively small, low
molecular weight proteins. Ex. 2016 ¶ 87; Ex. 2015 ¶ 260. A
POSA [person of ordinary skill in the art] may have considered
such low molecular weight antibody fragments, such as Fab
fragments, to have useful pharmacokinetic characteristics for
neutralizing small toxins. Ex. 2016 ¶ 87. However, Crotalus
toxins are significantly larger than cobrotoxins. Ex. 2016 ¶ 88.
Due to both their low molecular weight, and their monovalent
(single antigen-binding) nature, which could render them
unable to cross-link to larger molecules, a [person of ordinary
skill in the art] would have been concerned that Fab fragments
would not be effective against these larger molecules. Id.
Thus, a [person of ordinary skill in the art] would not have
IPR2015-01305
Patent 8,048,414 B1

18

applied the teaching in Chang of compositions comprising Fab
fragments to the pursuit of antivenom for the Crotalus genus.
Prelim. Resp. 37 (citing Ex. 2016 (Rebuttal Report of Dr. Richard C. Dart);
Ex. 2015 (Rebuttal Report of Professor Stephen MacKessy)).
Petitioner does not address the similarities and/or differences between
cobrotoxin, the dominant, relatively small toxin in cobra venom, and the
toxins in Crotalus toxin. Moreover, Petitioner has not explained adequately
why Chang’s disclosure would have given one of ordinary skill in the art a
reason, at the time of the invention, to develop an Fab fragment-based
antivenom pharmaceutical composition against Crotalus venom in the first
place, particularly in light of the WHO Report, which teaches explicitly that
“international standard antivenoms . . . should be an almost pure F(ab)2
plasma fraction.” Ex. 1006, 37.
Having considered the arguments and evidence presented with the
Petition, we are not persuaded that Petitioner has established a reasonable
likelihood of prevailing in its challenge to claims 1–7, 9–18, and 20–22 on
the basis of obviousness over Chang and the WHO Report.
E. Claims 8 and 19—Asserted Obviousness over Chang,
the WHO Report, and Smith
1. Smith (Ex. 1007)
Smith discusses the immunogenicity and kinetics of distribution and
elimination of digoxin-specific IgG and Fab fragments, and teaches that
“digoxin-specific Fab fragments undergo more rapid and extensive
distribution to the extracellular compartment and also more rapid renal
IPR2015-01305
Patent 8,048,414 B1

19

excretion than IgG” and “are significantly less immunogenic than the parent
IgG population.” Ex. 1007, 1. Smith teaches that “[r]elatively rapid
clearance of Fab fragments can be used to advantage when the objective is
rapid neutralization and clearance of a toxic substance.” Id. at 10.
2. Analysis
Petitioner contends that a person of ordinary skill in the art “would
have recognized that Fab fragments are particularly suited for treating snake
bite victims because they act quickly on toxins and are effective at
neutralizing snake venoms.” Pet. 48 (citing Ex. 1002 ¶ 134). Petitioner
contends “because of the rapid clearance of Fab fragments, to obtain
continued control of the toxic effect from snake venoms,” a person of
ordinary skill in the art “would have been motivated to make and administer
a composition comprising Fab and F(ab)2 fragments.” Id. (citing Ex. 1002
¶¶ 135–139. Dr. Kossiakoff asserts that a person of skill in the art “would
have understood that the pharmacokinetic properties of Fab and IgG or
F(ab)2 would complement each other.” Ex. 1002 ¶ 139.
To the extent this challenge is based on Chang and the WHO Report,
it suffers from the same infirmity as that discussed above. Further, as in the
ground discussed above, Petitioner does not address the similarities and/or
differences between digoxin and the toxins in Crotalus toxin, even though
the Smith reference was asserted in a rejection against the claims during
prosecution of the ’414 patent, a similar issue was raised, and the rejection
was ultimately withdrawn. See, e.g., Ex. 1016, 1194–95, 1538–39. Thus,
IPR2015-01305
Patent 8,048,414 B1

20

Petitioner has not explained adequately how Smith cures the infirmity in
Petitioner’s proposed combination of Chang and the WHO Report
Having considered the evidence and arguments presented in the
Petition, we are not persuaded that Petitioner has established a reasonable
likelihood of prevailing in its challenge to claim 8 and 19 on the basis of
obviousness over Chang, the WHO Report, and Smith.
F. Motion to Seal
Patent Owner’s Preliminary Response (Paper 12) was accompanied by
a Motion to Seal its Preliminary Response and Exhibit 2033, an associated
exhibit (Paper 14, “Motion to Seal”), and a redacted version of the
Preliminary Response (Paper 13).
As we did not rely on the material Patent Owner sought to seal, we
decline to address the merits of the Motion to Seal. Patent Owner is
authorized to file a motion to expunge any material that it seeks to keep
confidential within thirty (30) days of the date of this decision, or within
thirty (30) days of a decision on rehearing, if rehearing is requested.
III. CONCLUSION
For the foregoing reasons, we are not persuaded that the Petition
establishes a reasonable likelihood that Petitioner would prevail in showing
claims 1–22 of the ’414 patent are unpatentable under 35 U.S.C. § 103(a).
IPR2015-01305
Patent 8,048,414 B1

21

IV. ORDER
Accordingly, it is
ORDERED that the Petition is denied and no inter partes review is
instituted.

IPR2015-01305
Patent 8,048,414 B1

22

For PETITIONER:
Vincent Shier
Robert Mattson
John Kern
CPDocketShier@oblon.com
CPDocketMattson@oblon.com
CPDocketKern@oblon.com

Kenneth Darnell
kdarnell@graceba.net

For PATENT OWNER:
Michael Siekman
Lawrence Green
Oona Johnstone
MSiekman-PTAB@wolfgreenfield.com
LGreen-PTAB@wolfgreenfield.com
OJohnstone-PTAB@wolfgreenfield.com