Coalition for Affordable Drugs V LLCv.Hoffmann-La Roche Inc.

Patent Trial and Appeal Board

Mar 11, 2016

08444791 (P.T.A.B. Mar. 11, 2016)

Trials@uspto.gov Paper 14
Tel: 571-272-7822 Entered: March 11, 2016

UNITED STATES PATENT AND TRADEMARK OFFICE

BEFORE THE PATENT TRIAL AND APPEAL BOARD

COALITION FOR AFFORDABLE DRUGS V LLC,
Petitioner,
v.
HOFFMAN-LaROCHE INC.,
Patent Owner.

Case IPR2015-01792
Patent 8,163,522 B1

Before SUSAN L. C. MITCHELL, BRIAN P. MURPHY, and
TINA E. HULSE, Administrative Patent Judges.
MITCHELL, Administrative Patent Judge.

DECISION
Denying Institution of Inter Partes Review
37 C.F.R. § 42.108
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I. INTRODUCTION
A. Background
Petitioner Coalition for Affordable Drugs V LLC (“Petitioner”) filed a
petition (Paper 1, “Pet.”) to institute an inter partes review of claims 1–10
(the “challenged claims”) of U.S. Patent No. 8,163,522 B1 (Exhibit 1001,
the “’522 patent”). See 35 U.S.C. §§ 311–319. Patent Owner Hoffman-
LaRoche Inc. and Real Parties-in-Interest, Immunex Corporation and
Amgen Inc. (collectively, “Patent Owner”), filed a Preliminary Response.
Paper 10 (“Prelim. Resp.”).
We have jurisdiction under 35 U.S.C. § 314. To institute an inter
partes review, we must determine that the information presented in the
Petition shows “a reasonable likelihood that the petitioner would prevail
with respect to at least 1 of the claims challenged in the petition.” 35 U.S.C.
§ 314(a). For the reasons set forth below, we conclude that Petitioner has
not established a reasonable likelihood that it would prevail in showing the
unpatentability of any challenged claim of the ’522 patent. Therefore, we do
not institute an inter partes review for any challenged claim of the ’522
patent.
B. Related Proceedings
The parties identify a court proceeding involving the ’522 patent,
which has been terminated. See Sandoz Inc. v. Amgen Inc., 773 F.3d 1274
(Fed. Cir. 2014); Pet. 2; Paper 8, 2. Patent Owner also states that a
complaint asserting infringement of the ’522 patent was filed on February
26, 2016 in the United States District Court of New Jersey. See Immunex
Corp. v. Sandoz Inc., Case No. 2:16-cv-01118-CCC-JBC (D.N.J.). Paper
13, 2.
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C. The ’522 Patent (Ex. 1001)
The ’522 patent is directed in part to polynucleotides encoding the
extracellular region of an insoluble human TNF receptor (also, “TNF-R”)
described by an apparent molecular weight and as containing particular
amino acid sequences in addition to all domains of the constant region of a
human IgG1 immunoglobulin heavy chain except the first domain of the
heavy chain constant region. Ex. 1001, Abs., 2:26–49. The ’522 patent also
addresses methods for culturing a host cell comprising the polynucleotide
and purifying the expression product of the polynucleotide from the cell. Id.
D. Illustrative Claims
Claims 1 and 4 are illustrative of the claimed subject matter. Claims 1
and 4 are reproduced below.
1. A method comprising the steps of:
(a) culturing a host cell comprising a polynucleotide, wherein
the polynucleotide encodes a protein consisting of:

(i) the extracellular region of an insoluble human TNF
receptor, wherein the insoluble human TNF receptor has an
apparent molecular weight of about 75 kilodaltons as
determined on a non-reducing SDS-polyacrylamide gel and
comprises the amino acid sequence
LPAQVAFXPYAPEPGSTC (SEQ ID NO: 10), and

(ii) all of the domains of the constant region of a human
IgG immunoglobulin heavy chain other than the first domain of
said constant region, and

(b) purifying an expression product of the polynucleotide from
the cell mass or the culture medium.

4. A polynucleotide encoding a protein consisting of:

(a) the extracellular region of an insoluble human TNF receptor,
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wherein the insoluble human TNF receptor (i) has an
apparent molecular weight of about 75 kilodaltons as
determined on a non-reducing SDS-polyacrylamide gel and (ii)
comprises the amino acid sequence
LPAQVAFXPYAPEPGSTC (SEQ ID NO: 10), and

(b) all of the domains of the constant region of a human IgG1
immunoglobulin heavy chain other than the first domain of said
constant region.
E. Prior Art References Applied by Petitioner
Petitioner challenges the patentability of claims 1–10 on the basis of
the following references:
Capon et al. (“Capon”) 5,116,964 May 26, 1992 Ex. 1002
Smith et al. (“Smith”) 5,395,760 Mar. 7, 1995 Ex. 1003
Seed (“Seed”) 6,004,781 Dec. 21, 1999 Ex. 1006
F. The Asserted Ground of Unpatentability
Petitioner contends that the challenged claims 1–10 are unpatentable
under 35 U.S.C. § 103(a) based on Seed, Smith, and Capon (Pet. 22–60).

II. ANALYSIS
A. Claim Interpretation
In an inter partes review, claim terms in an unexpired patent are given
their broadest reasonable construction in light of the specification of the
patent in which they appear. 37 C.F.R. § 42.100(b). 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). An inventor
may rebut that presumption by providing a definition of the term in the
specification with reasonable clarity, deliberateness, and precision. In re
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Paulsen, 30 F.3d 1475, 1480 (Fed. Cir. 1994). In the absence of such a
definition, limitations are not to be read from the specification into the
claims. In re Van Geuns, 988 F.2d 1181, 1184 (Fed. Cir. 1993).
Petitioner proposes constructions for the terms “TNF receptor,” “all of
the domains of the constant region of a human IgG [or human IgG1]
immunoglobulin heavy chain other than the first domain of said constant
region,” and “about.” Pet. 13–14. Patent Owner also addresses the
appropriate construction for these terms. Prelim. Resp. 20–22.
1. “TNF receptor”
Petitioner offers that “TNF receptor” should be interpreted to mean
“soluble or non-soluble proteins, or fragments thereof which bind TNF, in
homogenous form.” Pet. 13 (citing Ex. 1004 ¶ 21 (citing Ex. 1001, 4:14–
18)). Patent Owner responds that the passage from the Specification of the
’522 patent cited by Petitioner’s Declarant, Dr. James J. Greene, see Ex.
1001, 4:14–18, refers to “proteins of the present invention,” or TNF fusion
proteins and not to TNF receptors. Prelim. Resp. 20–21. Patent Owner
offers that “TNF receptor” should be given its plain and ordinary meaning of
a receptor that binds TNF. Id. at 21. We agree that “TNF receptor” should
be given its ordinary meaning, but we are not persuaded that this claim
limitation needs an express construction at this stage of the proceeding.
2. “all of the domains of the constant region of a human IgG
immunoglobulin heavy chain other than the first domain of said
constant region” and “all of the domains of the constant region
of a human IgG1 immunoglobulin heavy chain other than the
first domain of said constant region”
Petitioner asserts that the claim phrase “all of the domains of the
constant region of a human IgG immunoglobulin heavy chain other than the
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first domain of said constant region” should be interpreted as “‘-hinge-CH2-
CH3’ region of an IgG (or IgG1) immunoglobulin heavy chain.” Pet. 14
(citing Ex. 1004 ¶ 22 (citing Ex. 1001, 2:37–43)). Patent Owner agrees with
the construction with two caveats: (1) that the reference to IgG should refer
to claims 1 and 7, and the reference to IgG1 should refer to claim 4; and
(2) that IgG and IgG1 be limited to human origin. Prelim. Resp. 21–22.
As all of the claims refer to human IgG or IgG1 immunoglobulin
heavy chain, see Ex. 1001, 45:58–60, 46:53–55, 47:1–3 and Petitioner
acknowledges this fact in its discussion concerning claim construction, Pet.
14 (referring to claim phrase denominating “human IgG immunoglobulin”),
the parties do not appear to disagree that the required IgG or IgG1
immunoglobulin heavy chain recited in the claims refers to human IgG or
IgG1 immunoglobulin heavy chain. Also, claims 1–3 and 7–10 of the ’522
patent refer to human IgG, see Ex. 1001, 45:58–60, 47:1–3, and claims 4–6
of the ’522 patent refer to human IgG1, see id. at 46:53–55. We agree with
Patent Owner that the construction for the claims should reflect this
distinction.
Dr. Greene provides a schematic for immunoglobulin structure
showing a heavy chain with a variable region followed by a constant region,
denominated CH1, a hinge region, and two other constant regions,
denominated CH2 and CH3. Ex. 1004 ¶ 24; see also Ex. 2009, 1, Fig. 3.1
(showing same structure for IgG). Dr. Greene also relies on a statement in
the ’522 Specification that states that “[t]his invention comprises DNA
sequences which combine two partial DNA sequences, one sequence
encoding soluble fragments of TNF binding proteins and the other partial
sequence encoding all domains except the first domain of the constant region
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of the heavy chain of human immunoglobulin IgG, IgA, IgM, or IgE, and the
recombinant proteins encoded by these sequences.” Ex. 1004 ¶ 22 (citing
Ex. 1001, 2:37–43).
Both parties appear to agree that all the domains of the constant region
of either human IgG or IgG1 other than the first domain of said constant
region includes a hinge region, and CH2 and CH3 constant regions. See Pet.
14; Prelim. Resp. 21–22, 12 (stating claims in related U.S. Patent 8,063,182
B1 (“the ’182 patent”) that includes similar claim language “are directed to
proteins that fuse a soluble fragment of p75 TNF receptor to the hinge, CH2,
and CH3 domains of human immunoglobulin”). Based on the record before
us, we construe “all of the domains of the constant region of a human IgG
immunoglobulin heavy chain other than the first domain of said constant
region” to mean “‘-hinge-CH2-CH3’ region of a human IgG immunoglobulin
heavy chain,” and “all of the domains of the constant region of a human
IgG1 immunoglobulin heavy chain other than the first domain of said
constant region” to mean “’-hinge-CH2-CH3’ region of a human IgG1
immunoglobulin heavy chain.”
3. “about”
Petitioner offers an interpretation of “about” as used in the claims to
mean “approximately.” Pet. 14. Although Patent Owner does not disagree
with the construction, it questions whether such construction is necessary.
Prelim. Resp. 22. We agree with Patent Owner that we do not need an
express construction of “about” at this stage of the proceeding.
B. Principles of Law
A patent claim is unpatentable under 35 U.S.C. § 103(a) if the
differences between the claimed subject matter and the prior art are such that
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the subject matter, as a whole, would have been obvious at the time the
invention was made to a person having ordinary skill in the art to which said
subject matter pertains. KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 406
(2007). The question of obviousness is resolved on the basis of underlying
factual determinations including: (1) the scope and content of the prior art;
(2) any differences between the claimed subject matter and the prior art;
(3) the level of ordinary skill in the art; and (4) objective evidence of
nonobviousness. Graham v. John Deere Co., 383 U.S. 1, 17–18 (1966).
In that regard, an obviousness analysis “need not seek out precise
teachings directed to the specific subject matter of the challenged claim, for
a court can take account of the inferences and creative steps that a person of
ordinary skill in the art would employ.” KSR, 550 U.S. at 418; see
Translogic, 504 F.3d at 1259. A prima facie case of obviousness is
established when the prior art itself would appear to have suggested the
claimed subject matter to a person of ordinary skill in the art. In re Rinehart,
531 F.2d 1048, 1051 (CCPA 1976). We are mindful that the level of
ordinary skill in the art also is reflected by the prior art of record. See
Okajima v. Bourdeau, 261 F.3d 1350, 1355 (Fed. Cir. 2001); In re GPAC
Inc., 57 F.3d 1573, 1579 (Fed. Cir. 1995); In re Oelrich, 579 F.2d 86, 91
(CCPA 1978).
We analyze the asserted ground of unpatentability in accordance with
the above-stated principles.
C. Obviousness over Smith, Capon, and Seed
Petitioner contends that claims 1–10 are unpatentable under 35 U.S.C.
§ 103 as obvious over Seed, Smith, and Capon. Pet. 4. Petitioner asserts
that Smith teaches IgG fusions containing the soluble derivatives of the full-
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length, human TNF receptor. Id. at 17 (citing Ex. 1003, 4:12–16).
Petitioner also asserts that both Seed and Capon teach fusions using the
hinge-CH2-CH3 regions of the constant region of the human immunoglobulin
heavy chain. Id. at 15–17 (citing Ex. 1006, 4:47–5:29, 6:13–14, 14:6–9; Ex.
1002, 4:38–47, 10:10–12, 40:65–69; Ex. 1004 ¶¶ 25, 26). Petitioner asserts
that “Smith’s soluble TNF receptor would be suitable as a ligand-binding
partner in the hybrids of Seed and Capon. The need for ‘practical yields’
would have motivated one to use Seed or Capon to express the TNF-R gene
of Smith.” Id. at 18 (citing Ex. 1004 ¶ 28). Petitioner also asserts that
enhanced TNF binding affinity as taught by Smith for dimeric assemblies,
see Id. (citing Ex. 1003, 10:61–66; Ex. 1004 ¶ 29), would also have
motivated a person of ordinary skill to use Seed or Capon to provide dimeric
TNF-R-Fc assemblies. Id.
1. Smith
Smith teaches DNA sequences encoding human tumor necrosis factor
receptors (TNF-R), see Ex. 1003, 2:38–41, recombinant expression vectors
comprising these DNA sequences, and also isolated or purified protein
compositions comprising soluble forms of TNF-R. Id. at 2:59–61. Smith
also states that
A recombinant chimeric antibody molecule may also be
produced having TNF-R sequences substituted for the variable
domains of either or both of the immunogl[o]bulin molecule
heavy and light chains and having unmodified constant region
domains. For example, chimeric TNF-R/IgG1 may be produced
from two chimeric genes—a TNF-R/human κ light chain
chimera (TNF-R/Cκ) and a TNF-R/human γ1 heavy chain
chimera (TNF-R/Cγ-1). Following transcription and translation
of the two chimeric genes, the gene products assemble into a
single chimeric antibody molecule having TNF-R displayed
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bivalently. Such polyvalent forms of TNF-R may have
enhanced binding affinity for TNF ligand.
Id. at 10:53–66.
2. Capon
Capon teaches polypeptides comprising a ligand binding partner fused
to a stable plasma protein, such as an immunoglobulin constant domain,
which is capable of extending the in vivo plasma half-life of the ligand
binding partner when present as such a fusion. Ex. 1002, 5:13–21. Capon
states that
Ordinarily, the ligand binding partner is fused C-
terminally to the N-terminus of the constant region of
immunoglobulins in place of the variable region(s) thereof,
however, N-terminal fusions of the binding partner are also
desirable. . . .
Typically, such fusions retain at least functionally active
hinge, CH2 and CH3 domains of the constant region of an
immunoglobulin heavy chain. Fusions are also made to the C-
terminus of the Fc portion of a constant domain, or immediately
N-terminal to the CH1 of the heavy chain or the corresponding
region of the light chain. . . .
The precise site at which the fusion is made is not
critical: particular sites are well known and may be selected in
order to optimize the biological activity, secretion or binding
characteristics of the binding partner. The optimal site will be
determined by routine experimentation.
In some embodiments the hybrid immunoglobulins are
assembled as monomers or hetero- or homo-multimers, and
particularly as dimers or tetramers.
Ex. 1002, 10:1–29.
In describing a particularly preferred embodiment, Capon states that
this embodiment
is a fusion of an N-terminal portion of a LHR, which contains
the binding site for the endothelium of lymphoid tissue, to the
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C-terminal Fc portion of an antibody, containing the effector
functions of immunoglobulin G1. There are two preferred
embodiments of this sort: in one, the entire heavy chain
constant region is fused to a portion of the LHR; in another, a
sequence beginning in the hinge region just upstream of the
papain cleavage site which defines IgG Fc chemically . . . is
fused to a portion of the LHR. The latter embodiment is
described in the Example 4.
Id. at 15:4–18. The murine LHR-IgG chimeras of Example 4 describe
truncated proteins of murine LHR that
are all joined to a human heavy chain gamma 1 region just
upstream of the hinge domain (H) such that these chimeras
contain the two cysteine residues (C) of the hinge responsible
for immunoglobulin dimerization as well as the CH2 and CH3
constant regions. . . . Junctional sites between the LHR and
human IgG sequences was chosen such that the joining of the
molecules near the hinge region resulted in chimeric molecules
that were efficiently synthesized and dimerized in the absence
of any light chain production.
Id. at 40:43–55.
3. Seed
Seed describes a DNA sequence encoding a fusion protein of CD4, or
a fragment of CD4, which binds to HIV gp120, and an immunoglobulin light
or heavy chain where the CD4 or fragment thereof replaces the variable
region of the light or heavy immunoglobulin chain. Ex. 1006, 4:48–53.
Seed specifically defined “fusion protein” as
a fused protein comprising CD4, or fragment thereof which is
capable of binding to gh120, linked at its C-terminus to an
immunoglobulin chain wherein a portion of the N-terminus of
the immunoglobulin is replaced with CD4. In general, that
portion of immunoglobulin which is deleted is the variable
region. The fusion proteins of the invention may also comprise
immunoglobulins where more than [j]ust the variable region
has been deleted and replaced with CD4 or HIV gp120 binding
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fragment thereof. For example, the VH and CH1 regions of an
immunoglobulin chain may be deleted. Preferably, any amount
of the N-terminus of the immunoglobulin heavy chain can be
deleted as long as the remaining fragment has antibody effector
function. The minimum sequence required for binding
complement encompasses domains CH2 and CH3. Joining of
Fc portions by the hinge region is advantageous for increasing
the efficiency of complement binding.
Id. at 6:4–21. Seed also defines “antibody effector function” as the
ability to fix, complement, or to activate antibody-dependent cellular
toxicity. Id. at 5:56–57.
4. Analysis
Petitioner presents an explanation demonstrating where the limitations
of the challenged claims may be found in the cited references. Pet. 15–60.
Petitioner also relies on the Declaration of James J. Green, Ph.D.
Petitioner’s argument focuses on how the combination of cited references
teach a polynucleotide consisting of the extracellular region of an insoluble
human TNF receptor and all of the domains of the constant region of a
human IgG or IgG1 immunoglobulin heavy chain other than the first domain
of said constant region.
For instance, Petitioner states that Smith discloses a TNF receptor,
and Seed and Capon each discloses receptors linked to IgG1 upstream from
the hinge region, with Capon defining the hinge region functionally. Id. at 4.
Petitioner concludes that
Once Smith had disclosed the TNF-R gene, a POSITA would
have used Capon’s method to make TNF-R-Fc with a
reasonable expectation of success:

[X receptor]-Fc (dimer) → [TNF receptor]-Fc (dimer)

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wherein [X receptor] is CD4 (Ex. 1002, 44:60–62; 45:6–12,
Example 5 of Capon), or cell surface glycoprotein lymphocyte
homing receptor of “LHR” (Ex. 1002, 15:4–8; 40:30–32,
Example 4 of Capon). Ex. 1004, ¶36.
Id. at 7. Petitioner also asserts that Capon discloses a “typical”
approach, set forth in examples 4 and 5 and Figure 8 of the
Specification of the ’522 patent, of omitting the CH1 domain from the
constant region of IgG. See id. at 8–9. Petitioner concludes that
“[m]odifying such chimeras by replacing their receptors with Smith’s
TNF-R required no selection from among multitudes. (It merely
required using Capon’s method for its intended purpose.[)] [(]Ex.
1004, ¶36[)].” Id. at 8.
Petitioner addresses a teaching away argument concerning
Smith made by Patent Owner during prosecution of the ’522 patent.
Petitioner asserts that, although Smith teaches unmodified IgG heavy
chains, Smith teaches this structure as just one embodiment, “giving
no reason why any other structure should be avoided.” Id. at 10
(citing Ex. 1020, 40:2–6; Ex. 1022, 24:16–20; Ex. 1024, 9:16–18).
Petitioner’s Declarant, Dr. Greene testifies that neither Smith nor
Capon “discourages the POSITA from using Capon’s method to make
Smith’s TNF-R.” Id. at 11 (citing Ex. 1004 ¶¶ 53, 76, 98).
Finally, Petitioner noted the unexpected properties of p75
TNFR fusions as compared to properties of soluble, recombinant
forms of p75 TNFR, but did not address the unexpected properties
substantively. Id. at 10–11; see also Ex. 1020, 33–36; Ex. 1024, 9–
13. Petitioner asserts that the evidence of unexpected results is
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unavailing because the claims are not commensurate in scope.
Pet. 10. Petitioner states:
Claims 1–10 are not commensurate in scope with any
protein because: (1) they are directed to either polynucleotides,
host cells, vectors, or methods of protein expression, but not to
proteins per se, and (2) all of the claimed subject matter has
alternative uses that were obvious over Seed, Smith, and Capon.
Id. at 11.
Patent Owner responds that institution of an inter partes review
should be denied because Petitioner has failed to demonstrate a reasonable
likelihood that it would prevail in demonstrating that the challenged claims
are rendered obvious over the combination of Smith, Capon, and Seed1 for
the following three reasons: (1) the Petition presents no new art that was not
considered previously by the Office; (2) the Petition did not explain
adequately why one of skill in the art would combine teachings of the
references to arrive at the claimed invention; and (3) the Petitioner failed to
address Patent Owner’s evidence of unexpected results presented in the
prosecution history of the ’522 patent. Prelim. Resp. 3–4.
Patent Owner asserts that both Capon and Seed teach fusion proteins
that retain the hinge, CH2, and CH3 domains of the constant region of an
immunoglobulin heavy chain to target and destroy unwanted cells. Id. at 8.
Patent Owner concludes that “[i]ndeed, the common message in both Seed

1 Petitioner acknowledges that Smith and Capon were before the Office
during prosecution of the ’522 patent, but asserts that Seed was not, see
Pet. 4. Patent Owner asserts, however, that the substantive teachings of
Seed were before the Office because a related Seed patent application,
EP 0 325 262, which shares the same disclosure as the Seed reference
asserted by Petitioner, was before the Office during the prosecution of the
’522 patent. Prelim. Resp. 8 (citing Ex. 2015; Ex. 2018, 2).
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and Capon is to create therapeutic fusion proteins by combining pro-
inflammatory receptors with pro-inflammatory IgG components, not
therapeutic fusion proteins that combine an anti-inflammatory receptor with
a pro-inflammatory Fc fragment.” Id. at 9. Smith provides no further
guidance to combine the teachings of the references, Patent Owner asserts,
because Smith teaches chimeric antibody molecules that incorporate
unmodified constant region domains. Id. Patent Owner concludes that the
combination of references would have led the skilled person away from the
claimed methods. Id.
We agree with Patent Owner that Petitioner has not shown a
reasonable likelihood to prevail on any challenged claim. Petitioner has
failed to show an articulated reason with a rational underpinning why one of
skill in the art would have combined the teachings of Smith, Capon, and
Seed to arrive at the claimed invention.
We agree with Patent Owner that the generalized guidance in Seed
and Capon would not have led one of ordinary skill in the art to produce a
p75 TNFR-based fusion protein having a structure that corresponds to the
expression products of the challenged claims or the protein encoded by the
polynucleotides described in the challenged claims. See Ex. 1001, 45:45–
48:4. For instance, Capon describes utilizing all of the heavy chain constant
region of an immunoglobulin or deleting the CH1 portion, but does not
distinguish the hinge-CH2-CH3 construct as offering any advantage that
would lead one of skill in the art to choose it in making a p75 TNFR-based
fusion protein. See Ex. 1002, 10:1–26. In fact, Capon specifically states
that the precise site at which the fusion protein is made is not critical, but
can be determined by routine experimentation. Id.
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Seed offers no better guidance for one of skill in the art in arriving at
the claimed invention. For instance, Seed also teaches that, in general, the
entire heavy chain constant region of the immunoglobulin may be used. See
Ex. 1006, 6:4–21. As an alternative, Seed states that more than the variable
region may be deleted and replaced, such as the CH1 portion of the constant
region, so long as the remaining fragment has antibody effector function. Id.
Petitioner’s offer of a rationale to combine the references is
unavailing. Petitioner offers that one of skill in the art would have been
motivated to use the teachings of Seed or Capon to express the TNF-R gene
of Smith, see Pet. 18 and Ex. 1004 ¶ 28, but fails to offer persuasive
evidence to explain why one of skill in the art would choose the Fc portion
of the immunoglobulin heavy chain from the choices taught in Seed or
Capon.
Petitioner offers only generalized teachings from the references to
show a rationale to combine. For instance, Smith states that practical yields
of its fusion protein may be obtained “only by cloning and expressing genes
encoding the receptors using recombinant DNA technology.” Pet. 17–18
(citing Ex. 1003, 2:22–25). From this statement, Petitioner concludes that
“[t]he need for ‘practical yields’ would have motivated one to use Seed or
Capon to express the TNF-R gene of Smith,” see id. at 18 (citing Ex. 1004
¶ 28), but such motivation does not provide a reason for one of skill in the
art to select the hinge-CH2-CH3 constant region of the immunoglobulin from
the teachings of Seed or Capon to combine with Smith’s TNF-R gene.
Petitioner also offers Smith’s teaching that polyvalent forms of
TNF-R may have enhanced binding affinity for a TNF ligand as a
motivation to combine the teaching of the references to arrive at the claimed
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invention, see Pet. 18 (citing Ex. 1006, 6:53–56), but Smith teaches use of
the entire constant region of the immunoglobulin to achieve such binding
affinity. This teaching would not point to selective deletion of the CH1
domain to achieve any enhanced binding affinity, and as we discussed
above, neither Capon nor Seed point to why one of skill in the art would
choose to use the -hinge-CH2-CH3 portion of the constant region of the
immunoglobulin over other constructs. Capon’s teaching of a prolonged in
vivo plasma half-life of the ligand binding partner is not linked to the use of
the -hinge-CH2-CH3 portion of the constant region of the immunoglobulin
over other constructs. See id. at 16 (quoting Ex. 1002, 4:38–47), 20.
Therefore, this would not provide a sufficient reason to combine the
references to achieve the claimed invention. Petitioner has not shown that it
is reasonably likely to prevail with respect to any challenged claim in the
Petition.
Petitioner also does not address adequately the objective indicia of
nonobviousness presented to the Office during the prosecution of the ’522
patent, merely asserting that such evidence was not commensurate in scope
with the claims. Id. at 10–11.2 Petitioner states that the claims are directed
to polynucleotides, host cells, vectors, and methods of protein expression,
while the unexpected results evidence addresses fusion proteins. Id. at 11.

2 Petitioner does assert that the claimed subject matter of the ’522 patent
“has alternative uses that were obvious over Seed, Smith, and Capon.”
Pet. 11. Petitioner, however, does not provide any explanation as to what
these alternative uses are. As this statement is mere attorney argument, we
give it little weight. See Meitzner v. Mindick, 549 F.2d 775, 782 (CCPA
1977) (stating “[a]rgument of counsel cannot take the place of evidence
lacking in the record”).
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The challenged method claims, however, address purifying a fusion protein
“expression product” encoded by the polynucleotide set forth in the claim,
see Ex. 1001, 45:45–67, 46:59–48:4, and the remaining challenged claims
address the polynucleotides encoding the fusion proteins. See id. at 46:44–
58; see also Ex. 1023, 13–143 (addressing presented unexpected results after
noting that the claimed inventions were “drawn to nucleic acids, not
proteins” (emphasis omitted)). The evidence of unexpected results is
commensurate in scope with the claims.
During the prosecution of the ’522 patent, Patent Owner offered
expert testimony concerning the unexpected results of improved TNF
binding affinity, potency, kinetic stability, and reduced antibody effector
function and aggregation ability. See Ex. 1020, 27–36; Ex. 1022, 25–39; Ex.
1024, 9–13; Ex. 2017. We agree with Patent Owner that the unrebutted
objective indicia of nonobviousness presented in the prosecution history of
the ’522 patent, and apparently relied upon by the Examiner, at least in part,
in allowing the claims of the ’522 patent, see Ex. 1026, 6, supports the non-
obviousness of the challenged claims. The Petition, moreover, should have
addressed the evidence of unexpected results as part of Petitioner’s showing
of a reasonable likelihood of success on the merits.4 See Praxair Distrib.,
Inc. v. INO Therapeutics, Inc., Case Nos. IPR2015-00522, -00524, -00525, -
00526, slip op. at 16–17 (PTAB July 29, 2015).

3 The cited pages refer to Petitioner’s pagination of the exhibit as opposed to
the original page numbers for the exhibit.
4 Because we have addressed the Petition on its merits, we need not address
whether to exercise our discretion under 35 U.S.C. § 325(d).
IPR2015-01792
Patent 8,163,522 B1
19
III. CONCLUSION
For the foregoing reasons, we are not persuaded that the Petition
establishes a reasonable likelihood that Petitioner would prevail in showing
any of claims 1–10 of the ’522 patent are unpatentable under 35 U.S.C.
§ 103(a).
IV. ORDER
Accordingly, it is
ORDERED that the Petition is denied at to all challenged claims of
the ’522 patent.

IPR2015-01792
Patent 8,163,522 B1
20
PETITIONER:
Robert W. Hahl
Robert Mihail
John K. Pike
NEIFELD IP LAW, PC
rhahl@neifeld.com
rmihail@neifeld.com
jkpike@neifeld.com
PATENT OWNER:
Jeffrey P. Kushan
James A. High
Jill J. Schmidt
Peter S. Choi
SIDLEY AUSTIN LLP
IPRNotices@sidley.com
jhigh@sidley.com
jschmidt@sidley.com
peter.choi@sidley.com