Ex Parte Chen et al

Board of Patent Appeals and Interferences

Jun 10, 2009

11302208 (B.P.A.I. Jun. 10, 2009)

UNITED STATES PATENT AND TRADEMARK OFFICE
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BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
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Ex parte BAO-LU CHEN and CHIN-YI HUANG
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Appeal 2009-001877
Application 11/302,208
Technology Center 1600
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Decided:1 June 10, 2009
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Before DEMETRA J. MILLS, RICHARD M. LEBOVITZ, and
JEFFREY N. FREDMAN, Administrative Patent Judges.

FREDMAN, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving an aqueous
composition. We have jurisdiction under 35 U.S.C. § 6(b). We affirm-in-
part.

1 The two-month time period for filing an appeal or commencing a
civil action, as recited in 37 C.F.R. § 1.304, begins to run from the
decided date shown on this page of the decision. The time period
does not run from the Mail Date (paper delivery) or Notification
Date (electronic delivery).

Appeal 2009-001877
Application 11/302,208

Statement of the Case
Background
“Tissue factor pathway inhibitor (TFPI) is 276 amino acids in length
and functions as an inhibitor of tissue factor-mediated blood coagulation”
(Spec. 1 ¶ 03). The Specification teaches that “[u]se of TFPI has been
proposed for the treatment of various indications, including sepsis . . . deep
vein thrombosis . . . ischemia . . . restenosis . . . and cancer” (Spec 1-2 ¶ 04).
According to the Specification, “compositions of TFPI or a TFPI variant can
be packaged for storage in an aqueous form or in a frozen state” (Spec. 2 ¶
05).
The Claims
Claims 1 and 8-32 are on appeal. Claims 1, 29, and 31 are
representative and read as follows:

1. An aqueous composition comprising:
Tissue Factor Pathway Inhibitor (TFPI) or ala-TFPI;
arginine in an amount sufficient to stabilize said TFPI
or ala-TFPI; and
methionine in a concentration from 2 mM to 10 mM
in said composition.

29. The composition [of claim 1, further comprising a
buffer] wherein said buffer comprises an acid in its salt
form.

31. The composition [of claim 1, further comprising a
buffer] wherein said buffer has a concentration from about 5
mM to about 30 mM.

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Application 11/302,208

The prior art
The Examiner relies on the following prior art reference to show
unpatentability:
Chen et al US 7,030,086 B2 Apr. 18, 2006

The issue
The Examiner rejected claims 1 and 8-32 on the ground of
nonstatutory obviousness-type double patenting as being unpatentable over
claims 1-15 of Chen (Ans. 4-5).
The Examiner finds that “[a]lthough the conflicting claims are not
identical, they are not patentably distinct from each other because the claims
of the pending application are encompassed by the genus of a composition
disclosed in the claims of the issued U.S. Patent No. 7,030,086 B2” (Ans. 4).
Appellants separately argue three groups, claims 1 and 8-28, claims
29 and 30, and claims 31 and 32. Appellants contend that “the ‘086 patent
claims fail to disclose any particular methionine concentration in a TFPI or
ala-TFPI composition, let alone a concentration of 2 mM to 10 mM, as
recited in the pending claims” (App. Br. 11).
Appellants contend that “[c]laims 29 and 30 are patentable for the
additional reason that the ‘086 patent claims do not suggest a composition
having a buffer comprising (i) ‘an acid in its salt form,’ as recited in claim
29 or (ii) ‘sodium citrate,’ as recited in claim 30.” (App. Br. 15).
Appellants contend that “[c]laims 31 and 32 are patentable for the
additional reason that the ‘086 patent claims do not suggest a buffer having
‘a concentration from about 5 mM to about 30 mM,’ as recited in claim 31
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or having ‘a concentration of about 20 mM,’ as recited in claim 32” (App.
Br. 16).
In view of these conflicting positions, we frame the obviousness-type
double patenting issues before us as follows:
Did the Examiner err in finding that the compositions of claims 1, 29,
and 31 are an obvious variant of the patented composition of claims 1-15 of
Chen?
Findings of Fact (FF)
1. Claim 1 of Chen reads as follows:
A liquid pharmaceutical composition comprising
tissue factor pathway inhibitor (TFPI) or variant
thereof as a therapeutically active component, wherein
said composition has been prepared by a method
comprising the step of combining said TFPI or variant
thereof with at least one amino acid and a buffering
agent that is an acid substantially free of its salt form,
wherein said amino acid is at least one of amino acids
arginine in its free base form and lysine in its free
base, said composition has a pH within a range of
about pH 4.0 to about pH 9.0, and said variant thereof
has at least 70% sequence identity with said TFPI as
calculated using the ALIGN program with a PAM 120
weight residue table, a gap length penalty of 12, and a
gap penalty of 4.

(Chen, col. 41, ll. 7-19.)
2. Claim 1 of Chen is drawn to an aqueous composition
comprising TFPI and arginine, but does not teach the presence of methionine
(see FF 1).
3. Claim 1 of Chen teaches that the buffering agent is “an acid
substantially free of its salt form” (see FF 1).
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Application 11/302,208

4. Claim 13 of Chen teaches “[t]he composition of claim 1, further
comprising methionine in an amount sufficient to inhibit oxidation of at least
one methionine residue in said TEPI [sic, TFPI] or variant thereof during
storage of said composition.” (Chen, col. 41, ll. 53-56.)
5. Claim 9 of Chen teaches “[t]he composition of claim 8, wherein
about 175 mM to about 400 mM arginine in its free base form and about 40
mM to about 200 mM citric acid are combined with said TEPI [sic TFPI] or
variant thereof.” (Chen, col. 41, ll. 41-44.)
6. Chen teaches that “the stabilized liquid pharmaceutical
composition comprises IL-2 or variant thereof as the polypeptide, arginine
base . . . methionine at a concentration of about 0.5 mM to about 10 mM”
(Chen, col. 11, ll. 29-34).
7. Chen teaches that “[a]s shown in Table 10, the presence of 5
mM methionine in the formulation results in a 3-fold decrease in the level of
peak A both at 4° C. and at 25° C. Thus, addition of 5 mM methionine
effectively prevented the Met104 from oxidation” (Chen, col. 31, ll. 63-67).
Principles of Law
Obviousness-type double patenting … requires
rejection of an application claim when the claimed
subject matter is not patentably distinct from the
subject matter claimed in a commonly owned patent.
Its purpose is to prevent an unjustified extension of
the term of the right to exclude granted by a patent by
allowing a second patent claiming an obvious variant
of the same invention to issue to the same owner later.

In re Berg, 140 F.3d 1428, 1431-1432 (Fed. Cir. 1998) (citations omitted).
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The question of obviousness is resolved on the basis of underlying
factual determinations including: (1) the scope and content of the prior art;
(2) the level of ordinary skill in the art; (3) the differences between the
claimed invention and the prior art; and (4) secondary considerations of
nonobviousness, if any. Graham v. John Deere Co., 383 U.S. 1, 17 (1966).
The Supreme Court has recently emphasized that “the [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
Int'l Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007).
“If a person of ordinary skill can implement a predictable variation, §
103 likely bars its patentability.” Id. at 417. As noted by the Court in KSR,
“[a] person of ordinary skill is also a person of ordinary creativity, not an
automaton.” 550 U.S. at 421.
“[O]ur predecessor court stated that a patent's disclosure may be used
to determine whether an application claim is merely an obvious variation of
an invention claimed in a patent. Vogel, 422 F.2d at 441-42. The court stated
that the disclosure may be used to learn the meaning of terms and in
‘interpreting the coverage of [a] claim.’” In re Basell Poliolefine Italia
S.P.A., 547 F.3d 1371, 1378 (Fed. Cir. 2008).
Analysis
Claim 1
Claim 13 of Chen, which directly depends from Claim 1 of Chen,
teaches a composition which comprises TFPI, arginine, and “methionine in
an amount sufficient to inhibit oxidation of at least one methionine residue
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in said TEPI [sic TFPI] or variant thereof during storage of said
composition” (Chen, col. 41, ll. 53-56; FF 1, 2, 4).
Following the analysis of the court in Basell, the disclosure of the
Chen patent is used to determine how an ordinary practitioner would
understand and interpret the meaning of the term “methionine in an amount
sufficient to inhibit oxidation of at least one methionine residue” in Claim 13
of Chen. See In re Basell Poliolefine Italia S.P.A, 547 F.3d at 1378 (“[T]he
disclosure may be used to learn the meaning of terms and in ‘interpreting the
coverage of [a] claim.’”)
Chen teaches a range of methionine concentrations which may be
added to the composition which overlaps the range recited in Appellants’
Claim 1 (FF 6). Chen also teaches one value of methionine which is
sufficient to inhibit oxidation, a value of 5 mM (FF 7). We agree with the
Examiner that the case law in Basell and Vogel supports the analysis where
“one of skill in the art would look to the specification to define the
‘sufficient amount’ of methionine intended in the claim” (Ans. 7). The
ordinary artisan would recognize that a value of 5 mM, at least, is intended
by Claim 13 of Chen.
Appellants have not shown any criticality in the range of 2mM to
10mM of methionine in claim 1 which distinguishes this range from the
disclosure of Claim 13 of Chen that includes a value of 5 mM of methionine.
The law is replete with cases in which the difference
between the claimed invention and the prior art is
some range or other variable within the claims….
These cases have consistently held that in such a
situation, the applicant must show that the particular
range is critical, generally by showing that the
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Application 11/302,208

claimed range achieves unexpected results relative to
the prior art range.

In re Woodruff, 919 F.2d 1575, 1578 (1990) (internal citations omitted).
We are not persuaded by Appellants’ argument that “[p]rima facie
obviousness also generally requires some suggestion or motivation, either in
the reference or in the knowledge available to one of ordinary skill in the art,
to modify the reference teachings” (App. Br. 13). In KSR, the Supreme
Court rejected the rigid application of the teaching, suggestion, and
motivation test by the Federal Circuit, stating that
The principles underlying [earlier] cases are
instructive when the question is whether a patent claiming
the combination of elements of prior art is obvious. When a
work is available in one field of endeavor, design incentives
and other market forces can prompt variations of it, either in
the same field or a different one. If a person of ordinary skill
can implement a predictable variation, § 103 likely bars its
patentability.

KSR, 550 U.S. at 417. We find that the ordinary artisan would have been
predictably able to modify the methionine concentration in claim 13 of Chen
to encompass 2mM to 10mM (FF 1, 2, 4, 6, 7).
We are not convinced by Appellants’ argument that the “inventors of
the present application have discovered important commercial benefits, in
terms of stabilization of TFPI or ala-TFPI compositions, which are
associated with the claimed combination of features” (App. Br. 14).
Appellants have not compared the claimed invention to claim 13 of Chen, as
properly interpreted, which is the closest prior art. See In re Baxter Travenol
Labs., 952 F.2d 388, 392 (Fed. Cir. 1991) (“[W]hen unexpected results are
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used as evidence of nonobviousness, the results must be shown to be
unexpected compared with the closest prior art.”).
Claim 29 and 30
The Examiner finds that “one skilled in the art would refer to a
disclosure of the ‘086 patent to further define the ‘buffering agent that is
substantially free of its salt form’ and here the disclosure of the ‘086 patent,
clearly teaches that a TFPI solution was formulated with 20 mM sodium
citrate” (Ans. 8).
However, Claim 29 specifically states that the “buffer comprises an
acid in its salt form” while Claim 1 of Chen specifically requires a
“buffering agent that is an acid substantially free of its salt form” (FF 1, 3).
In this case, the species of claim 29 is specifically excluded by Claim 1 of
Chen.
Here, in order to find obviousness, the Examiner must read Claim 1 of
Chen to encompass something which is specifically excluded by the plain
language of the claim. We therefore conclude that claims 29 and 30 are not
obvious variants of Claim 1 of Chen.
Claims 31 and 32
Appellants contend that “the ‘086 patent claims disclose significantly
higher concentrations of the ‘buffering agent’” than the amounts recited in
Claim 31 (App. Br. 16).
In fact, Claim 9 of Chen has a range of buffering agent which
encompasses at least about 40 mM of citric acid (FF 5). Appellants’ claim
31 encompasses a range of about 5 mM to about 30 mM (see Claim 31).
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Application 11/302,208

Appellants’ claim 32 is drawn to a buffer with a concentration of “about 20
mM” (Claim 32).
Our reviewing court stated in Peterson that
In cases involving overlapping ranges, we and our
predecessor court have consistently held that even a slight
overlap in range establishes a prima facie case of
obviousness …. We have also held that a prima facie case of
obviousness exists when the claimed range and the prior art
range do not overlap but are close enough such that one
skilled in the art would have expected them to have the same
properties. Titanium Metals Corp. v. Banner, 778 F.2d 775,
783 … (Fed.Cir.1985).

In re Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003). Here, the claimed
range and the prior art range, particularly as modified by the “about”
language, may not overlap, but are certainly reasonably understood as close
enough that one skilled in the art would have expected them to have the
same properties (see FF 5).
Additionally, Appellants have identified no criticality to the claimed
range values. See In re Woodruff, 919 F.2d at 1578. We therefore conclude
that Claims 31 and 32 are obvious over the disclosure of Claims 1 and 9 of
Chen.

Conclusion of Law
The Examiner did not err in finding that the composition of claim 1,
was an obvious variants of the patented composition of claims 1-15,
particularly claims 1 and 13 of Chen.
The Examiner erred in finding that the compositions of claims 29 and
30 are obvious variants of the patented composition of claims 1-15 of Chen.
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Application 11/302,208

The Examiner did not err in finding that the compositions of claims 31
and 32 are obvious variants of the patented composition of claims 1-15 of
Chen.
SUMMARY
In summary, we affirm the rejection of claims 1, 31 and 32 under
nonstatutory obviousness-type double patenting as being unpatentable over
claims 1-15 of Chen. Pursuant to 37 C.F.R. § 41.37(c)(1)(vii)(2006), we
also affirm the rejection of claims 8-28 as these claims were not argued
separately.
We reverse the rejection of claims 29 and 30 under nonstatutory
obviousness-type double patenting as being unpatentable over claims 1-15 of
Chen
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(1)(iv)(2006).

AFFIRMED-IN-PART

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