Ex Parte Burton et al

Patent Trial and Appeal Board

Feb 21, 2013

10514455 (P.T.A.B. Feb. 21, 2013)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte STEVEN JAMES BURTON, TADEUSZ PODGORSKI, and
SAJI S. EAPEN
__________

Appeal 2011-005121
Application 10/514,455
Technology Center 1600
__________

Before DONALD E. ADAMS, ERICA A. FRANKLIN, and
JACQUELINE WRIGHT BONILLA, Administrative Patent Judges.

BONILLA, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims directed to a
method of separating endotoxins from other biological compounds using a
ligand-matrix conjugate comprising tris(2-aminoethyl)amine as the ligand.
The Examiner has rejected the claims as anticipated. We have jurisdiction
under 35 U.S.C. § 6(b). We affirm.

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STATEMENT OF THE CASE
The Specification teaches that “endotoxins are lipopolysaccharides
(LPS) found in the outer membrane of gram-negative bacteria such as E.coli
(Spec 1). The Specification describes “the discovery of a novel class of
synthetic affinity ligand structures for the selective capture and removal of
endotoxin from solutions containing biological therapeutic products” (id. at
2). “The support matrix Z may be any compound or material, particulate or
non-particulate, soluble or insoluble, porous or non-porous” (id. at 4). A
ligand may be attached to the matrix via a spacer or directly (id.). Example
1 describes the preparation of tris(2-aminoethyl)amine - PuraBead® 6XL
(id. at 6-7).
Claims 1, 2, 5, 6, and 9-12 are on appeal. Independent claim 1 is
representative and reads as follows (emphasis added):
1. A method whereby endotoxins are separated from other biological
compounds in an aqueous system wherein said method comprises the
use of an affinity ligand-matrix conjugate of the structure
Z-Spacer-Ligand
wherein the ligand is tris(2-aminoethyl)amine; the spacer may
or may not be present; and the ligand is attached to a support matrix Z
directly or through the spacer,
and wherein the method comprises contacting the affinity ligand-
matrix conjugate with the aqueous system under conditions such that
endotoxins bind directly to the ligand thereby separating the
endotoxins from other biological compounds of the aqueous system.
The claims stand rejected under 35 U.S.C. §102(b) as anticipated by
Miwa et al. (EP 1 057 529 A1, published Dec. 6, 2000).
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Findings of Fact (FF)
1. Miwa describes
material having selective affinity for compounds produced by
prokaryotic micro-organisms, namely gram-negative bacteria and
gram-positive bacteria. From amongst the compounds produced by
bacteria, it relates to a material which removes or results in a loss of
toxic activity (detoxification) of lipoteichoic acid (hereinafter
abbreviated to LTA), protein A (hereinafter abbreviated to PrA) or α-
hemolysin (abbreviated to aHL).
(Miwa 2 [0001].)
2. Miwa discloses that
The present invention has the following constitution …
(1) A bacterially-derived component detoxification or removal
material which is characterized in that it has at least one functional
group capable of hydrogen bond formation and detoxifies or removes
at least one of the bacterially derived components selected from
lipoteichoic acid, protein A, α hemolysin and proteinase.
(2) A bacterially-derived component detoxification or removal
material which is characterized in that it has a functional group
capable of hydrogen bond formation and a hydrophobic group and/or
ether bond, and it detoxifies or removes at least one of the bacterially-
derived components selected from lipoteichoic acid, protein A, α
hemolysin, proteinase and endotoxin.
(id. at 2-3 [0006] (emphasis added).)
3. Miwa teaches that “there are no particular restrictions on the
functional groups capable of hydrogen bond formation, and examples are the
urea bond, thiourea bond, urethane bond, amide group, amino group,
hydroxyl group, carboxyl group, aldehyde group, mercapto group and
guanidino group” (id. at 3 [0009] (emphasis added)).
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4. Miwa teaches that “[a]s examples of structures with an amino group,
there are … tris(2-aminoethyl)amine and the like …” (id. at 3 [0009]).
5. Miwa discloses that “[a]s a functional group other than a group
capable of forming a hydrogen bond, it is preferred that there be present a
hydrophobic group or ether bond” (id. at 3 [0010]).
6. Example 1 in Miwa describes the production of “materials with amino
groups (a)(b), amino groups and ether groups (c), amino groups and
hydroxyl groups (d), and amino groups and hydrophobic groups (e) to (h),
introduced into a carrier fibre having amide bonds” (id. at 6 [0025] –
[0026]). Example 2 describes introducing urea groups, thiourea groups and
amide groups into chitosan beads (id. at 6-7 [0027] – [0028]). Example 3
describes introducing amino groups and hydrophobic groups into cellulose
beads (id. at 7 [0029] – [0030]). Example 4 shows that the material of
Examples, 1, 2 and 3 bind to endotoxins (id. at 8-9 [0031] – [0032]).
7. Miwa includes claims such as:
1. A bacterially-derived component detoxification or removal material
which is characterized in that it has one or more than one functional
group capable of hydrogen bond formation and detoxifies or removes
at least one of the bacterially-derived components selected from
lipoteichoic acid, protein A, α hemolysin, proteinase and endotoxin.
17. A material according to Claim 1 which is characterized in that it
has at least one hydrophobic group.
23. A material according to Claim 1 which is characterized in that it
has an ether bond.
(id. at 10-11 (emphasis added).)
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Principles of Law
The Examiner bears the initial burden, on review of the prior art or on
any other ground, of presenting a prima facie case of unpatentability. In re
Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992). If the Examiner meets that
initial burden, the burden of coming forward with evidence or argument
shifts to the applicant. In re Rijckaert, 9 F.3d 1531, 1532 (Fed. Cir. 1993).
After the applicant submits such evidence or argument, the PTO then
determines patentability “on the totality of the record, by a preponderance of
evidence with due consideration to persuasiveness of argument.” Oetiker,
977 F.2d at 1445.
In order for a prior art reference to serve as an anticipatory reference,
it must disclose every limitation of the claimed invention, either explicitly or
inherently. See, e.g., In re Schreiber, 128 F.3d 1473, 1477 (Fed. Cir. 1997).
Analysis
Appellants argue that claim 1 requires that “the ligand, to which
endotoxins bind directly, is tris(2-aminoethyl)amine” but Miwa “does not
disclose that endotoxins bind directly to tris(2-aminoethyl)amine” (App. Br.
2). Appellants assert that Miwa’s material for removing “endotoxins
comprises two components: 1) a functional group capable of hydrogen bond
formation, and 2) a hydrophobic group and/or ether bond,” citing Miwa,
page 3, lines 5-8 (id.) (see also (2) in FF 2 for cited passage). By contrast,
according to Appellants, “the ligand of the presently claimed invention is
tris(2-aminoethyl)amine (id.).
Along the same lines, Appellants assert that “[w]hile it may be true
that certain of the Miwa et al. ligands are said to bind to endotoxins, it is not
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true that all molecules mentioned by Miwa et al. would function as ligands
to bind to endotoxins” (id. at 4). Appellants then argue “[t]o the contrary,
Miwa et al. specifically state that, to separate endotoxins, the ligand must
have a hydrophobic group and/or an ether bond” (id.). According to
Appellants, Miwa only “teaches using tris(2-aminoethyl)amine as a reagent
that introduces a functional amino group into the removal material,”
referring to Examples 1-3 of Miwa in support, but the reference does not
teach that tris(2-aminoethyl)amine itself may act as a ligand that binds
directly to an endotoxin (id. at 4-5).
We conclude that the Examiner established a prima facie case of
anticipation. Along these lines, we adopt the fact findings and conclusions
of the Examiner as our own (Ans. 4-17). Like the Examiner, we find that
“the tris(2-aminoethyl)amine, cited by Miwa et al., is a polyamine having
three functional groups all capable of hydrogen bond formation” (id. at 6).
Likewise, Miwa teaches that the hydrogen bonds of tris(2-aminoethyl)amine
“bind the endotoxin,” and therefore Miwa teaches “the direct binding as
required by the claims” (id. at 6-7).
We also agree with the Examiner that Appellants point “to an
alternative material which Miwa et al. teaches. Paragraph [0010] states ‘As
a functional group other than a group capable of forming a hydrogen bond, it
is preferred that there be present a hydrophobic group or ether bond.’
Clearly, Miwa et al, is teaching additional embodiments” (id. at 7).
In other words, while Miwa teaches the embodiment that Appellants
discuss, i.e., a material comprising both 1) a functional group capable of
hydrogen bond formation, and 2) a hydrophobic group and/or ether bond,
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Miwa also describes relevant material comprising a functional group capable
of hydrogen bond formation (such as an amine group) in the absence of a
hydrophobic group and/or ether bond, where that material binds directly to
an endotoxin (FF 2-7). Contrary to assertions by Appellants (App. Br. 2;
Reply Br. 2-4), paragraph [0006] in Miwa does not dictate a different
finding. Rather, paragraph [0006] discloses both a material having “at least
one functional group capable of hydrogen bond formation” and a material
having “a functional group capable of hydrogen bond formation and a
hydrophobic group and/or ether bond” (see (1) and (2) in FF 2; see also
Miwa [0006]).
As the Examiner notes, paragraph [0010] in Miwa, especially when
read in light of the entire reference, indicates that a relevant ligand may have
“a hydrophobic group or ether bond” as an alternative to “a group capable of
forming a hydrogen bond” (Ans. 8; FF 5). We also note that claims
presented in Miwa’s patent application further teach that the “bacterially-
derived component detoxification or removal material” of claim 1
encompasses one that “has one or more than one functional group capable of
hydrogen bond formation” (FF 7). Material having such functional groups
include tris(2-aminoethyl)amine, as expressly described in Miwa’s
specification (FF 4). Independent claim 1 does not require the additional
elements required in dependent claims, i.e., “at least one hydrophobic
group” (claim 17) or “an ether bond” (claim 23).
We are not persuaded by Appellants’ argument to the contrary (Reply
Br. 3-4). While claim 1 in Miwa teaches two aspects, i.e., that the material
1) has a functional group capable of hydrogen bond formation, and 2) is
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capable of removing bacterially-derived components, Miwa does not teach
that these two aspects must be “separate and distinct elements” as asserted
by Appellants (id. at 3). Rather, Miwa as a whole teaches that material
having “one or more than one functional group capable of hydrogen bond
formation” removes endotoxins (FF 2-7). Such teachings do not impose the
requirement that the material comprise both a group capable of hydrogen
bond formation and a hydrophobic group or ether bond in order to be
capable of removing endotoxins.
Lastly, while Example 3 describes material having both a group
capable of hydrogen bond formation (amino group) and a hydrophobic
group, Examples 1 and 2 describes material having functional groups
capable of hydrogen bond formation alone (e.g., amino group with a carrier
having amide bonds (Example 1), or a urea, thiourea, or amide group
(Example 2)) (FF 6). Example 4 indicates that all prepared material in
Examples 1-3 bound to endotoxins (id.). Thus, in the Examples, consistent
with the rest of the disclosure, Miwa describes that material having
functional groups capable of hydrogen bond formation (even without having
a hydrophobic group or ether bond) will bind directly to endotoxins.
We conclude that the Examiner established by a preponderance of the
evidence that Miwa expressly teaches that tris(2-aminoethyl)amine itself
may act as a relevant ligand that binds directly to an endotoxin. Appellants
do not persuade us that the Examiner erred in concluding that Miwa
anticipates claim 1. Because Appellants do not argue claims 2, 5, 6, and 9-
12 separately, these dependent claims fall together with independent claim 1.
37 C.F.R. § 41.37(c)(1)(vii).
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SUMMARY
We affirm the rejection of claims 1, 2, 5, 6, and 9-12 as anticipated by
Miwa.

TIME PERIOD FOR RESPONSE
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).

AFFIRMED

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