3D-Matrix, Ltd.v.Menicon Co., Ltd.

Patent Trial and Appeal Board

Aug 1, 2014

11921746 (P.T.A.B. Aug. 1, 2014)

Trials@uspto.gov Paper 11
Tel: 571-272-7822 Entered: August 1, 2014

UNITED STATES PATENT AND TRADEMARK OFFICE
_______________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
_______________
3D-MATRIX, LTD,
Petitioner,
v.
MENICON CO., LTD,
Patent Owner.
_____________
Case IPR2014-00398
Patent 8,299,032 B2
_______________
Before JACQUELINE WRIGHT BONILLA, DONNA M. PRAISS, and
BRIAN P. MURPHY, Administrative Patent Judges.

MURPHY, Administrative Patent Judge.

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

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I. INTRODUCTION

On January 31, 2014, 3D-Matrix, Ltd. (“Petitioner”) filed a Petition
requesting inter partes review of claims 1-8 of U.S. Patent No. 8,299,032 B2
(“the ’032 patent”). Paper 1 (“Pet.”). On May 9, 2014, Menicon Co., Ltd.
(“Patent Owner”) filed a Preliminary Response to the Petition. Paper 9
(“Prelim. Resp.”). We have jurisdiction under 35 U.S.C. § 314(a), 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.”
Petitioner challenges claims 1-8 of the ’032 patent as unpatentable
under 35 U.S.C. §§ 102(b) and 103. Based on the information presented in
the Petition, Preliminary Response, and cited exhibits, we are not persuaded
there is a reasonable likelihood that Petitioner would prevail with respect to
at least one of the claims challenged in the Petition. On this record, we deny
the Petition to institute an inter partes review of claims 1-8 of the ’032
patent.
A. Related Proceedings
The parties do not identify any related proceedings regarding the ’032
patent.
B. The ’032 Patent (Ex. 2001)
The ’032 patent, titled “SELF-ASSEMBLING PEPTIDE AND GEL
PRODUCED FROM THE SAME,” issued October 30, 2012, from a PCT
application filed June 26, 2006. Ex. 2001. The self-assembling peptide
described in the ’032 patent is comprised of polar and nonpolar amino acid
residues, has a non-zero peptide charge at neutral pH, and forms a beta (ß)-
sheet structure in an aqueous solution. Id. at 1:49-60. The beta (ß)-sheet has
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one face of only nonpolar amino acid residues. Id. at 1:57-60. Self-
assembling peptide gels are useful, for example, as scaffolds for three
dimensional cell cultures. Id. at 2:67-3:3. The ’032 patent recites several
advantages resulting from the claimed peptide, including balanced
electrostatic forces to prevent “excessive association,” transparency of
scaffolds, ease of preparation, and beta (ß)-sheet (membrane) stability. Id. at
2:33-67.
The ’032 patent states that the charge of the self-assembling peptide is
pH-dependent and can be calculated according to the method of Lehninger.
Id. at 6:1-7. The calculation is typically executed using a computer program.
Id. Table 8 of the ’032 patent identifies nine exemplary peptides having
SEQ ID Nos. 1-9, and Table 9 lists the charge for each peptide at pH 7.0,
calculated according to the method of Lehninger. 1 Id. at 17:17-18:18. The
calculated charges for SEQ ID Nos. 1-9 are all non-zero, namely +2, +3, or -
2. Id. at 18:1-18.
Claim 1 of the ’032 patent, the only independent challenged claim, is
representative and reproduced below (emphasis added).
1. A self-assembling peptide comprising polar amino acid
residues and nonpolar amino acid residues,
wherein the self-assembling peptide consists of 12 to 32
amino acid residues, comprises one or more acidic amino acid
residues and one or more basic amino acid residues as the polar
amino acid residues,
wherein the sum of charge of the acidic amino acid
residue(s) and charge of the basic amino acid residue(s), when

1 Lehninger is the author of a text book titled “Principles of Biochemistry,”
referenced in the ’032 patent as “Lehninger [Biochemie, 1979].” Ex. 2001,
6:3.
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the self-assembling peptide is in a neutral pH environment, is
from -3 to -2 or +2 to +3, wherein all of the amino acids in the
self-assembling peptide form a beta (ß)-sheet structure in
which one face consists of only nonpolar amino acid residues
upon self-assembly in a neutral aqueous solution, and wherein
the nonpolar amino acid residues are selected from the group
consisting of alanine, glycine, leucine, isoleucine, methionine,
valine, phenylalanine, and tryptophan.

C. Prior Art Relied Upon in the Petition
Petitioner relies upon the following references:
Zhang II US 5,670,483 Sept. 23, 1997 Ex. 1002

Agelli WO 2004/007532 A2 Jan. 22, 2004 Ex. 1019

Altman 9 PROT. SCI. 1095-1105 2000 Ex. 1009

Dado 115 J. AM. CHEM. Soc. 12609-
610

1993 Ex. 1004
Mira 4 BMC STRUC. BIO. 7-21 June 4, 2004 Ex. 1021

Yokoi

102 PNAS 8414-19

June 14, 2005

Ex. 1016
Zhang I 90 PNAS 3334-38 April 1993 Ex. 1001

D. Asserted Grounds of Unpatentability
Petitioner asserts that the challenged claims are unpatentable based on
the following grounds:

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Reference[s] Basis Claims challenged
Dado § 102(b) 1-8
Altman § 102(b) 1-8
Zhang II, Yokoi, and
Agelli § 103
1-8
Mira and Zhang I §§ 102(b)
and 103
1-8
II. ANALYSIS
A. Claim Construction
In an inter partes review, we construe claim terms according to their
broadest reasonable interpretation in light of the patent specification.
37 C.F.R. § 42.100(b); Office Patent Trial Practice Guide, 77 Fed. Reg.
48,756, 48,766 (Aug. 14, 2012). Under the broadest reasonable
interpretation standard, we assign claim terms their ordinary and customary
meaning, as understood by one of ordinary skill in the art, in the context of
the entire patent disclosure. In re Translogic Tech., Inc., 504 F.3d 1249,
1257 (Fed. Cir. 2007). Any special definition for a claim term must be set
forth in the specification with reasonable clarity, deliberateness, and
precision. In re Paulsen, 30 F.3d 1475, 1480 (Fed. Cir. 1994).
Petitioner does not argue that any claim term in the ’032 patent should
take on a meaning other than its ordinary and customary meaning. Pet. 18-
23. Patent Owner does not address claim construction. Prelim. Resp. 6-8.
We proceed on the basis that the claim terms are given their ordinary and
customary meaning as understood by one of ordinary skill in the art in the
context of the ’032 patent.
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B. Anticipation of Claims 1-8 by Dado
Petitioner argues that the primary difference between the claimed
peptide and the prior art generally is the claimed charge of -3 to -2 or +2 to
+3 of the recited self-assembling peptide at neutral pH, versus a charge of
zero (0) for prior-art self-assembling peptides at neutral pH. Pet. 20; see
also id. at 15-17; Ex. 2001, 18:12 (describing prior art RADA16, i.e.,
Peptide No. 10, as having a net charge of 0 at pH 7). Petitioner states that
the charge difference of the claimed peptides results from substitution of at
least two, possibly three, ionic amino acid residues with non-ionic polar
amino acid residues (e.g., serine or asparagine) or alanine. Id. at 20.
Petitioner relies on Dado as disclosing such a substituted self-assembling
peptide and argues that Dado inherently anticipates claims 1-8 of the ’032
patent. Id. at 23-25.
“To establish inherency, the extrinsic evidence ‘must make clear that
the missing descriptive matter is necessarily present in the thing described in
the reference.’” In re Robertson, 169 F.3d 743, 745 (Fed. Cir.
1999)(quotation omitted). Inherency is not proven “by probabilities or
possibilities. The mere fact that a certain thing may result from a given set
of circumstances is not sufficient.” Id. (quotation omitted). We assess the
merits of Petitioner’s arguments and evidence in support of the asserted
inherency, according to the aforementioned standard.
1. Dado (Ex. 1004)
Dado discloses an 18-residue peptide, Peptide 1º, that contains one
acidic residue (glutamic acid (E)), three basic residues (lysine (K)), and
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nonpolar alanine (A) and leucine (L) residues.2 Ex. 1004, 12609 (left
column and Fig. 1). Peptide 1º is capable of forming a beta (ß)-sheet
structure having one face of only nonpolar residues upon self-assembly in an
aqueous solution. Id. at 12610, Fig. 2. The structure of Peptide 1º is not in
dispute. Prelim. Resp. 20-24. Petitioner recognizes that Dado does not
disclose (i) the charge of Peptide 1º in a neutral pH environment, or (ii) the
pH of the aqueous solution in which Peptide 1º forms a beta (ß)-sheet. Pet.
23-25; Ex. 1004. Petitioner argues, however, that Dado inherently satisfies
these two limitations of the ’032 patent claim 1. Patent Owner opposes.
Prelim. Resp. 20-24.
2. Anticipation Analysis
a. Charge of Peptide 1º
Claim 1 of the ’032 patent recites “wherein the sum of charge of the
acidic . . . and basic amino acid residue(s), when the self-assembling peptide
is in a neutral pH environment, is from -3 to -2 or +2 to +3.”3 Petitioner
states the charge of Dado’s Peptide 1º is “+2 in a neutral pH environment, as
calculated by Lehninger et al.” Pet. 23-24. Petitioner does not provide a
declaration or other documentary evidence in support of this statement. Id.
Petitioner relies on attorney argument to satisfy its burden of persuasion
regarding the peptide charge limitation of claim 1. Patent Owner responds
that, in the absence of a declaration and explanation of how the peptide
charge calculation was performed, Petitioner cannot rely on the asserted

2 The sequence is Ac-YLKAMºLEAMºAKLMºAKLMºA-NH2. Mº is a
polar, non-ionic, methionine sulfoxide residue. Ex. 1004, 12609.
3 Claims 2-8 depend from independent claim 1.
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charge of +2. Prelim. Resp. 23-24 (citing 37 CFR § 42.65(b)). We agree
with Patent Owner.
Section 42.65 governs expert opinion testimony, tests, and data on
which a party may rely in support of its position. 37 C.F.R. § 42.65.
Section 42.65(a) requires an expert who gives opinion testimony in an inter
partes review to “disclose the underlying facts or data on which the opinion
is based,” otherwise the opinion is entitled to little or no weight. Id.
§ 42.65(a). Section 42.65(b) provides that a party who relies on a technical
test or data from such a test “must provide an affidavit” explaining (i) why
the test or data is being used, (ii) how the test was performed and data
generated, (iii) how the data is used to determine a value, (iv) how the test is
regarded in the relevant art, and (v) any other information necessary for the
Board to evaluate the test and data. Id. § 42.65(b). The language of §42.65
evokes Federal Rule of Evidence 702, which permits expert testimony if
“scientific, technical, or other specialized knowledge will assist the trier of
fact to understand the evidence or to determine a fact in issue.”4
The overarching subject of an inquiry under Fed. R. Evid. 702 “is
scientific validity—and thus the evidentiary relevance and reliability—of the
principles that underlie a proposed submission.” Daubert v. Merrell Dow
Pharm., Inc., 509 U.S. 579, 594-95 (1993). Although a Daubert inquiry

4 Our Rules provide that “the Federal Rules of evidence shall apply to a
proceeding.” 37 C.F.R. § 42.62(a). The rationale is that “[t]he Federal
Rules of Evidence provide a well-developed body of recognized case law
that is reasonable for the Office to draw upon in administering these trial
rules,” and our reviewing courts are familiar with those rules. Rules of
Practice for Trials Before the Patent Trial and Appeal Board, 77 Fed. Reg.
48,612, 48,645 (August 14, 2012).
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pursuant to Fed. R. Evid. 702 is intended to relax the rigid “general
acceptance” requirement for admission of scientific evidence under Frye,5
the focus remains on assessing evidentiary trustworthiness, which is based
upon scientific validity. Id. at 590 n. 9; see also Dal-Tile Corp. v. United
States, 424 F.3d 1286, 1291-92 (Fed. Cir. 2005) (“The Court of International
Trade, in our view, properly examined the four factors enunciated in
Daubert to determine [test method] reliability . . . .”). The Board’s § 42.65,
as with Fed. R. Evid. 702, is intended to ensure that a party proponent meets
a threshold level of reliability when offering technical tests and data as
evidence.
The ’032 patent discloses the method of Lehninger as a preferred
method for calculating peptide charge. Ex. 2001, 6:1-3. The patent
indicates peptide charge is a pH-dependent calculation, and it cites an
exemplary web page for access to a software program that, presumably,
performs the Lehninger method of calculation. Id. at 6:1-7.6 Given that the
peptide charge computation is pH-dependent (pH is a logarithmic scale) and
executed via software, we determine that it is the type of technical data
governed by § 42.65(b).
Dado does not disclose a charge for Peptide 1º, whether or not in a
neutral pH environment. Because Petitioner’s statement—the charge of
Peptide 1º is +2 in a neutral pH environment as calculated by Lehninger et
al.—is not supported by a declaration, affidavit, or any further explanation,
we do not know how the peptide charge calculation was performed, the

5 Frye v. United States, 293 F. 1013, 1014 (1923).
6 The Board’s independent effort to access the cited web page resulted in a
message that the web page could not be found.
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precise method or formula used to calculate it, how the calculation method is
regarded in the relevant art, or any other information on which we might rely
to evaluate the scientific validity of the asserted charge for Peptide 1º. 37
CFR § 42.65(b); see also Daubert, 509 U.S. at 594-95. Therefore, we give
no weight to Petitioner’s unsupported statement that the charge of Peptide 1º
is +2 in a neutral pH environment, as calculated by Lehninger et al.
In sum, the record in this case does not contain sufficient evidence to
support Petitioner’s assertion that the charge of Peptide 1º in a neutral pH
environment is +2.
b. Inherency of beta (ß)-sheet formation in a neutral
aqueous solution
Claim 1 of the ’032 patent recites “wherein all of the amino acids in
the self-assembling peptide form a beta (ß)-sheet structure . . . upon self-
assembly in a neutral aqueous solution.” Ex. 2001, 23:30-34 (emphasis
added). The ’032 patent defines “neutral” as a pH from 6 to 8. Ex. 2001,
6:8-9. Petitioner acknowledges that Dado does not disclose the pH of the
aqueous solution in which beta (ß)-sheet conformation of Peptide 1º is
observed, but argues that Dado’s Peptide 1º inherently forms a stable beta-
sheet in a neutral aqueous solution. Pet. 24. Petitioner has chosen not to
submit a declaration in support of the Petition and, therefore, does not cite
any explanatory testimony in support of its inherency argument. See id. at
23-25.
Dado discloses that Peptide 1º forms a beta (ß)-sheet in “aqueous
solution,” without disclosing the pH of the solution. Ex. 1004, 12609.
Petitioner reasons that because Peptide 1º has the same structure as the
peptide claimed in the ’032 patent, and “given the totality of the evidence
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presented in the body of literature described above [Pet. 3-14], the person of
skill in the art would conclude that Peptide 1º inherently self-assembles at
neutral pH under the conditions explicitly taught by Zhang et al.7 for
structurally similar peptides.” Id. at 24. This is the sum and substance of
Petitioner’s inherency analysis.
Petitioner’s argument is conclusory and lacks persuasive detail,
evidentiary citations, and analysis. Petitioner does not explain or support,
with specific citations, why Dado’s Peptide 1º necessarily would form a beta
(ß)-sheet in a neutral aqueous solution, in view of Dado’s protein design
strategy and any particular teaching from any one of the Zhang references.
Pet. 23-25. For example, Dado does not disclose specific reaction
conditions for the methionine sulfoxide side chain reaction that drives beta
(ß)-sheet conformation of Peptide 1º. Ex. 1004; Prelim. Resp. 23.
Petitioner, however, does not explain how any one of the Zhang references
discloses reaction conditions for structurally similar peptides that would lead
a person skilled in the art to conclude that Peptide 1º necessarily self-
assembles into a beta (ß)-sheet in a neutral aqueous solution. Pet. 23-25.
Notably, Petitioner also does not address specific similarities (or
differences) among the peptides disclosed in the Zhang references, Peptide
1º, and the ’032 patent peptides, particularly in terms of structure, the
influence of pH or salt concentration, reaction conditions, charge, amino
acid sequence, or other properties. Id.; see Prelim. Resp. 23. Petitioner,
therefore, has not presented its inherency challenge with sufficient
particularity by specifying “where each element of the claim is found in the

7 We note that the Petition cites to sixteen different “Zhang” references. Pet.
3-14.
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prior art patents or printed publications relied upon.” Prelim. Resp. 5
(quoting 37 CFR § 42.104(b)(4)), 21(citing 35 U.S.C. § 312(a)(3)).
Petitioner further relies on In re Spada, 911 F.2d 705 (Fed. Cir. 1990)
in support of its inherency argument. Pet. 24. In Spada, the Federal Circuit
found that a claimed tackiness property of a pressure sensitive adhesive
composition was present inherently in the prior art because the prior art
polymer and the patent application polymer were the same, e.g., they used
identical monomers with overlapping amounts and employed the same or
similar polymerization techniques. Spada, 911 F.2d at 707-08. In the
present case, unlike in Spada, Petitioner does not assert that Dado discloses
or describes a peptide identical to any of the exemplary peptides disclosed in
the ’032 patent. Pet. 23-24; see also Prelim. Resp. 22.8 Petitioner also does
not assert that the reaction conditions under which Peptide 1º self-assembles
into a beta (ß)-sheet structure (Ex. 1004) are the same as those disclosed in
the ’032 patent (Ex. 2001, 15:45-17:7). Pet. 23-24. Thus, Spada is
inapposite here.
We conclude, therefore, that Petitioner’s attorney argument and
reliance on Spada, without specific factual and evidentiary support, is
insufficient for Petitioner to establish the asserted inherency of Peptide 1º
forming a beta (ß)-sheet structure upon self-assembly in a neutral aqueous
solution.
For the reasons given above, the Petition and evidence of record are
insufficient to persuade us of a reasonable likelihood that Petitioner would

8 Peptide 1º is not one of the nine exemplary peptides disclosed in the ’032
patent. See Ex. 2001, 17:20-33.
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prevail in showing Dado anticipates claims 1-8 of the ’032 patent under 35
U.S.C. §102(b).
C. Anticipation of Claims 1-8 by Altman
Petitioner asserts that claims 1-8 of the ’032 patent are inherently
anticipated by peptide EAK12-d disclosed in Altman. Pet. 25-29. Petitioner
asserts that EAK12-d has a -2 charge in a neutral pH environment, and
further argues that EAK12-d inherently forms a beta (ß)-sheet “in at least
one neutral pH environment, such as by adding salt, increasing peptide
concentration or increasing temperature.” Pet. 26-27. Patent Owner
opposes. Prelim. Resp. 24-28.
1. Altman (Ex. 1009)
Altman discloses a 12-residue peptide, EAK12-d, that contains four
acidic residues (glutamic acid (E)), two basic residues (lysine (K)), and
nonpolar alanine (A) residues.9 Ex. 1009, 1096 Table 1. EAK12-d is
capable of forming a beta (ß)-sheet structure having one face of only non-
polar residues, and “can undergo a secondary structure transformation from
ß-sheet to α-helix with either temperature or pH [change].” Id. at 1097; see
also, id. at 1099-1100. Altman discloses that EAK12-d “forms a ß-sheet at
pH 1-3 with a transition at pH 4, changing to a more helical structure at pH 5
and above.” Id. at 1100; see also, id. at 1099, Fig. 4 (“When EAK12-d is
incubated at pH 5-10, it exhibits an α-helical spectrum with about 30%
helical content.”). Altman does not disclose a charge for EAK12-d, whether
or not in a neutral pH environment. Id.

9 The sequence is Ac-AEAEAEAEAKAK-NH2.
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2. Anticipation Analysis
Petitioner asserts a charge of -2 for Altman’s EAK12-d peptide in a
neutral environment, without citation, declaration or affidavit support, or
further explanation of how the peptide charge was computed. Pet. 26.
Patent Owner again objects to Petitioner’s non-compliance with § 42.65(b).
Prelim. Resp. 27. For the same reasons discussed above, we conclude that
the record in this case does not contain sufficient evidence to support
Petitioner’s assertion that the charge of EAK12-d in a neutral pH
environment is -2. See 37 C.F.R. § 42.65(b).
Petitioner’s additional argument, that EAK12-d inherently forms a
beta (ß)-sheet in neutral aqueous solution, refers generally to a “large body
of art” without specific citations or analysis. Pet. 26-27. Petitioner’s
argument also is not consistent with Altman, because Altman discloses a
conformational change of EAK12-d from a beta (ß)-sheet at low pH to an α-
helix structure at pH 5 and above. Ex. 1009, 1099-1100; see also Prelim.
Resp. 26-27. Without additional evidentiary support and explanation of
Petitioner’s argument that EAK12-d necessarily forms a beta (ß)-sheet
structure in a neutral aqueous solution, we conclude Petitioner’s inherency
argument regarding Altman does not satisfy the standard articulated in In re
Robertson, 169 F.3d at 745.
For the reasons given above, the Petition and evidence of record are
insufficient to persuade us of a reasonable likelihood that Petitioner would
prevail in showing Altman anticipates claims 1-8 of the ’032 patent under 35
U.S.C. § 102(b).

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D. Obviousness of Claims 1-8 over Zhang II, Yokoi, and Agelli
Petitioner asserts that Zhang II’s EAK16 peptide (Ex. 1002, 1:30-48),
when modified by replacing at least two glutamic acid or lysine residues
with neutral hydrophilic or nonpolar residues, renders claims 1-8 of the ’032
patent obvious under 35 U.S.C. § 103. Pet. 29-33. Petitioner argues that
Agelli, reinforced by Yokoi, provides the teaching and reason for one of
ordinary skill in the art to make the modification, with a reasonable
expectation of successfully achieving the claim 1 peptide of the ’032 patent.
Pet. 31-33. Patent Owner opposes. Prelim. Resp. 28-30, 32-36.
Obviousness under 35 U.S.C. § 103 requires an assessment of (1) the
“level of ordinary skill in the pertinent art,” (2) the “scope and content of the
prior art,” (3) the “differences between the prior art and the claims at issue,”
and (4) “secondary considerations” of nonobviousness such as “commercial
success, long-felt but unsolved needs, failure of others, etc.” KSR Int’l Co.
v. Teleflex Inc., 550 U.S. 398, 406 (2007) (quoting Graham v. John Deere
Co., 383 U.S. 1, 17-18 (1966)). A party who petitions the Board for a
determination of obviousness must show that “‘a skilled artisan would have
been motivated to combine the teachings of the prior art references to
achieve the claimed invention, and that the skilled artisan would have had a
reasonable expectation of success from doing so.’” Proctor & Gamble Co.
v. Teva Pharms. USA, Inc., 566 F.3d 989, 994 (Fed. Cir. 2009) (quoting
Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1361 (Fed. Cir. 2007)). We
evaluate Petitioner’s evidence and argument according to the above-
articulated standard for obviousness.

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1. Zhang II (Ex. 1002)
Zhang II discloses a 16-residue peptide, EAK16, that contains four
acidic residues (glutamic acid (E)), four basic residues (lysine (K)), and non-
polar alanine (A) residues.10 Ex. 1002, 3:4-11, Fig. 1. EAK16 forms a beta
(ß)-sheet structure having alternating polar and nonpolar residues at pH 7.
Id. at 6:25-42, 13:29-46 (“The ß-sheet structure of EAK16 was also not
significantly affected by pH.”), Fig. 10 (pH profile confirms ß-sheet
conformation at pH 7). Zhang II does not disclose a charge for EAK16,
whether or not in a neutral pH environment. Id. Although the Petition does
not contain an affidavit or declaration setting forth how Petitioner calculated
a peptide charge of zero (0) for EAK16 (Pet. 30-31), both parties agree that a
difference between EAK16 and the peptide of claim 1 is the peptide charge
in a neutral pH environment. Pet. 31; Prelim. Resp. 28.
2. Obviousness Analysis
Petitioner contends that Zhang II teaches ionized pair formation
between complementary hydrophilic side chains on adjacent peptides and
the use of glutamine and asparagine (neutral residues) in place of charged
residues in membrane-forming peptides. Pet. 31. Petitioner concludes,
based on the teachings of Zhang II, that one of skill in the art would have
been motivated to “replace, remove or add 2 glutamic acid or 2 lysine
residues in the sequence of EAK16 and/or replace with neutral hydrophilic
residues, such as asparagine or glutamine, with a reasonable expectation that
the resulting peptide would form membranes.” Id. at 31-32. Petitioner
argues that, because Agelli teaches a peptide having alternating hydrophobic

10 The sequence is AEAEAKAKAEAEAKAK.
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and hydrophilic residues with two terminal hydrophilic residues and a
charge of -2,11 “one of skill in the art would not be deterred from replacing,
removing, or adding one or more ionic charges” to EAK16 and would expect
beta (ß)-sheet formation to occur. Pet. 32 (emphasis added). Petitioner’s
argument, however, does not satisfy the KSR/Graham standard for a
showing of obviousness under 35 U.S.C. § 103.
We agree with Patent Owner that, although Zhang II discloses EAK16
as forming a beta-sheet in a neutral aqueous solution (Ex. 1002, 13:8-46),
Petitioner does not address why one of skill in the art would have had reason
to modify the peptide as suggested and still expect to form a beta (ß)-sheet.
Prelim. Resp. 29. Petitioner does not explain and support, with precise
citations and/or declaration evidence, why one of skill in the art would have
had reason to replace two ionic charged residues in EAK16, glutamic acid or
lysine, with two neutral hydrophilic residues such as asparagine or
glutamine. Pet. 31-32; Prelim. Resp. 34-35. The Petition also does not
assert, or support with an adequate explanation or declaration evidence, that
the modified EAK16 peptide would have a charge of -3 to -2 or +2 to +3 in a
neutral pH environment, as required by claim 1 of the ’032 patent. Pet. 31-
33; Prelim. Resp. 30. Therefore, in the absence of supporting testimony, or
a more in-depth analysis of the teachings of Zhang II, Agelli, and Yokoi
supported with precise citations, we are not persuaded that Petitioner has
made a sufficient showing of obviousness for claims 1-8 of the ’032 patent.
For the reasons given above, the Petition and evidence of record are
insufficient to persuade us of a reasonable likelihood that Petitioner would

11 Petitioner does not support its peptide charge calculation for Agelli with
an affidavit or declaration.
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prevail in showing Zhang II, Agelli, and Yokoi render claims 1-8 of the ’032
patent obvious under 35 U.S.C. § 103.
E. Anticipation of Claims 1-8 by Mira or Obviousness of Claims 1-8
over Mira and Zhang I
Petitioner argues that Mira’s Peptide-1 (Ex. 1021, 3 (Fig. 1B), 5)
either anticipates claims 1-8 of the ’032 patent, or, when modified by
replacing three threonine residues with three nonpolar (hydrophobic)
residues, renders the claims obvious under 35 U.S.C. § 103. Pet. 33-36.
Petitioner argues, in particular, that the Board should adopt “the definition of
Zhang I,” which “clearly teaches that threonine, for purposes of self-
assembling peptides, is hydrophobic and can be used in lieu of alanine,
leucine, phenylalanine or the like.” Id. at 35 (emphasis added). The issue
raised by this argument is whether threonine should be considered
“nonpolar” for purposes of satisfying the claim limitation, “wherein all of
the amino acids in the self-assembling peptide form a beta (ß)-sheet structure
in which one face consists of only nonpolar amino acid residues.” Ex. 2001,
23:30-33 (emphasis added). Patent Owner opposes. Prelim. Resp. 30-31,
36-38.
1. Mira (Ex. 1021)
Mira discloses a 20-residue peptide, Peptide-1, that contains six acidic
residues (4 glutamic acid (E) and 2 aspartic acid (D)) and four basic residues
(lysine (K)).12 Ex. 1021, 3 (Fig. 1B). The nonpolar residues are alanine (A)
and valine (V). Id. The hydrophobic face of Peptide-1 contains three
threonine residues (T). Id. at 3, Fig. 1D. Threonine is defined as a polar

12 The sequence is Ac-YKTEAETKTEAKVDAKADVE-NH2.
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residue in the ’032 patent. Ex. 2001, 4:16 (Table 1). Mira also identifies
threonine as a polar residue. Ex. 1021, 3, Fig. 1A (polar amino acids
indicated by open circle).
Mira characterizes the circular dichroism spectrum of Peptide-1 at
neutral pH and 10ºC as an “extended ß-sheet secondary structure,” but at
acidic pH values there is a conformational transformation “towards the
stabilization of a ß-sheet secondary structure that produces a canonical ß-
sheet CD spectrum.” Ex. 1021, 6. Mira does not disclose a charge for
Peptide-1, whether or not in a neutral pH environment. Id. The Petition
does not contain an affidavit or declaration setting forth how Petitioner
calculated a charge of -2 for Peptide-1 at neutral pH. Pet. 34.
2. Analysis
Petitioner cites to column 6, lines 29-30, of Zhang I in support of its
argument that threonine should be considered a “nonpolar” amino acid.
Zhang I, however, is not a patent, does not have column and line numbers,
and does not support Petitioner’s statement. See Ex. 1001. We infer that
Petitioner intended to cite Zhang II at column 6, lines 29-30, which provides
that “[t]he hydrophobic amino acids include Ala, Val, Ile, Met, Phe, Tyr,
Trp, Ser, Thr, and Gly.” Ex. 1002, 6:29-30 (emphasis added). Even so, we
agree with Patent Owner that the ’032 patent specification clearly identifies
threonine as a polar amino acid (Prelim. Resp. 37), and the concluding
Markush group of nonpolar residues in claim 1 also omits threonine.
Ex. 2001, 23:34-37. Petitioner’s invocation of Zhang II, column 6, lines 29-
30, is insufficient to reach a different conclusion, because Zhang II states
only that threonine is one of several hydrophobic amino acids; it does not
state that threonine should be considered a non-polar amino acid. The fact
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that Mira itself characterizes threonine as polar, rather than nonpolar, weighs
even more heavily against Petitioner’s interpretation of threonine. The
weight of the evidence of record, therefore, indicates that threonine is a
“polar” amino acid as recited in claim 1, consistent with the ordinary
meaning of “polar” in the context of the Specification of the ’032 patent
under the broadest reasonable interpretation standard. See Translogic Tech.,
504 F.3d at 1257 (“The specification ‘is the single best guide to the meaning
of a disputed term.’” (quoting Phillips v. AWH Corp., 415 F.3d 1303, 1315
(Fed. Cir. 2005))).
We again note the absence of an affidavit or declaration to support the
asserted charge of -2 for Mira’s Peptide-1. Pet. 34; Prelim. Resp. 31. Thus,
we give Petitioner’s assertion in this regard no weight. The Petition and
evidence of record also are insufficient for us to conclude that Petitioner has
a reasonable likelihood of establishing that Mira, even in view of Zhang II
(or Zhang I), discloses, describes, or suggests formation of “a beta (ß)-sheet
structure in which one face consists of only nonpolar amino acid residues
upon self-assembly in a neutral aqueous solution.” We conclude, therefore,
that the Petition and evidence of record are insufficient to persuade us of a
reasonable likelihood that Petitioner would prevail in showing that Mira
anticipates claims 1-8 of the ’032 patent under 35 U.S.C. § 102(b), or that
Mira and Zhang I or Zhang II render the claims obvious under 35 U.S.C.
§ 103.
III. CONCLUSION
Petitioner has not shown that there is a reasonable likelihood it would
prevail with respect to at least one of the claims challenged in this Petition
based on the grounds asserted therein. Therefore, the Petition is denied.
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IV. ORDER
For the reasons given, it is
ORDERED that the Petition challenging the patentability of claims 1-
8 of U.S. Patent No. 8,299,032 is denied.

Petitioner:
Carolyn S. Elmore, Lead Counsel
Darlene A. Vanstone, Backup Counsel
ELMORE PATENT LAW GROUP, P.C.
celmore@elmorepatents.com
dvanstone@elmorepatents.com

Patent Owner:
Patrick A. Doody, Lead Counsel
Bryan P. Collins, Backup Counsel
PILLSBURY WINTHROP SHAW PITTMAN LLP
Patrick.doody@pillsburylaw.com
Bryan.collins@pillsburylaw.com