Ex Parte Hanson et al

Board of Patent Appeals and Interferences

Jun 20, 2009

10954951 (B.P.A.I. Jun. 20, 2009)

UNITED STATES PATENT AND TRADEMARK OFFICE
_________________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
_________________

Ex parte GEORGE HANSON, WIESLAW ANTONI KUDLICKI,
and SHIRANTHI KEPPETIPOLA

Appellants
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Appeal 2009-003032
Application 10/954,951
Technology Center 1600
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Decided1: June 22, 2009
_________________

Before RICHARD TORCZON, SALLY GARDNER LANE and MICHAEL
P. TIERNEY, Administrative Patent Judges.

LANE, Administrative Patent Judge.

DECISION ON APPEAL

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).

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I. STATEMENT OF THE CASE
The appeal, under 35 U.S.C. § 134, is from a Final Rejection of claims
4, 6-14, 16, 17, and 28-32. Claims 18-27 were withdrawn as being drawn to
non-elected subject matter. (App. Br. 1). Claims 1-3, 5, and 15 were
cancelled. (Id.). We have jurisdiction under 35 U.S.C. § 6(b). We affirm.
Appellants claim a kit and in vitro synthesis system comprising an
extract from a bacterial cell that is mutant for the SlyD gene.
The Examiner relied on the following documents.
Name Number Date
Chatterjee 2002/0168706 November 14, 2002
Genentech WO 97/46696 December 11, 1997
The Examiner also relied on the following publications:
• Stryer, Biochemistry, 646-48 (1975) (“Stryer”).
• Gromet-Elhanan et al., “ATP Synthesis and Hydrolysis by a
Hybrid System Reconstituted from the β-Subunit of Escherichia
coli F1-ATPase and β-less Chromatophores of Rhodospirillum
rubrum,” 260 J. Biol.Chem. 12635-40 (1985) (“Gromet-
Elhanan”).
• Wülfing et al., “An Escherichia coli Protein Consisting of a
Domain Homologous to FK506-binding Proteins (FKBP) and a
New Metal Binding Motif,” 269 J. Biol. Chem. 2895-2901
(1994) (“Wülfing”).
• Roof et al., “Mutational analysis of slyD, an Escherchia coli
gene encoding a protein of the FKBP immunophilin family,”
25 Mol. Microbiol. 1031-46 (1997) (“Roof”).
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• Adams et al., “New Biarsenical Ligands and Tetracysteine
Motifs for Protein Labeling in Vitro and in Vivo: Synthesis and
Biological Applications,” 124 J. Am. Chem. Soc. 6063-76
(2002) (“Adams”).
The Examiner rejected claims 4, 6-8, 10, 12-14, 16, 17, and 28-32
under 35 under 35 U.S.C. § 103(a) over Genentech, Wülfing, Roof, and
Adams. Because Appellants did not argue for the separate patentability of
any of the rejected claims, we focus on claim 28 as a representative claim.
See 37 C.F.R. § 41.37(c)(1)(vii).
The Examiner also rejected claim 9 under 35 U.S.C. § 103(a) over
Genentech, Wülfing, Roof, Adams, and Chatterjee, and claim 11 under
35 U.S.C. § 103(a) over Genentech, Wülfing, Roof, Adams, Stryer, and
Gromet-Elhanan.
II. LEGAL PRINCIPLES
“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 Int’l Co. v. Teleflex, Inc.,
550 U.S. 398, 417 (2007).
III. ISSUE
Would those of skill in the art have found it obvious to make a cellular
extract from a bacterial cell having a mutant SlyD gene for in vitro
synthesis?
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IV. FINDINGS OF FACT AND ANALYSIS
Claim 28
Findings of Fact
1. Appellants’ claim 28 recites:
An in vitro synthesis system comprising:

a cellular extract from a bacterial cell having a mutant SlyD
gene, wherein the cellular extract is substantially free of a slyD
polypeptide that binds to a bi-arsenical reagent;

amino acids; and

at least one energy source providing chemical energy for
synthesis.

(App. Br. 11, Claims App’x).
2. Roof teaches mutations of the SlyD gene that prevent the
polypeptide from being made in E. coli. (Roof 1035, paragraph bridging
col. 1 and 2; Table 1).
3. Genentech teaches in vitro protein synthesis using bacterial
extracts from E. coli. (Genentech 2, ll. 13-14; 9, ll. 2-6).
4. Genentech teaches adding amino acids and an energy source to
the extract for in vitro protein synthesis. (Genentech 9, ll. 17-19).
5. Wülfing teaches that a protein with the same sequence as the
slyD polypeptide is a “major contaminant” in immobilized metal affinity
chromatography of recombinant proteins made in E. coli because it has
many potential metal binding amino acids. (Wülfing abstract and 2895, left
col., second paragraph).
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Analysis
The in vitro synthesis system recited in Appellants’ claim 28
comprises a bacterial cellular extract that is substantially free of the slyD
polypeptide because the SlyD gene of the bacteria has been mutated.
(FF2 1). The system also has amino acids and an energy source. (FF 1).
Thus, bacterial extracts that are substantially free of slyD polypeptide due to
a mutation in the gene, and can be used for in vitro synthesis with added
amino acids and energy, meet the limitations of Appellants’ claimed system.
We note that Appellants’ claims do not limit the efficiency of the system.
Roof teaches E. coli bacteria with mutations in the SlyD gene that
prevent production of slyD polypeptide. (FF 2). Genentech teaches that in
vitro protein synthesis systems can be made from bacterial extracts (FF 3),
with added amino acids and energy sources. (FF 4). Those of skill in the art
would have expected extracts of the bacteria in Roof to support in vitro
protein synthesis as taught in Genentech because both are based on E. coli.
(FF 3). Those of skill in the art would have had a reason to substitute
extracts from the SlyD mutant bacteria of Roof for those used in Genentech
because Wülfing teaches that slyD protein is a contaminant for recombinant
protein purification from bacterial cell extracts using immobilized metal
affinity chromatography. (FF 5). Thus, use of extracts from the cells taught
in Roof, in a system such as that taught in Genentech, is a predictable
variation, which would have been obvious given the “design incentives and
other market forces” known to those in the art. See KSR, 550 US at 417.

2 Finding of fact.
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Appellants cite Wülfing and Roof to show that those of skill in the art
would have known that the slyD protein is a member of the FKBP family of
rotamases, which are considered to be important for promoting correct
protein conformation. (App. Br. 6). According to Appellants, this function
would have made it “unreasonable” to use an extract lacking slyD for in
vitro synthesis. (Id.).
Even though Wülfing and Roof speculate on the role of slyD
polypeptide in protein folding3, neither teaches that bacterial cells mutant in
the SlyD gene fail to make any correctly folded protein. In fact, the mutant
strains taught in Roof are able to grow, indicating at least some protein
synthesis. Appellants’ claim does not limit the efficiency or other
parameters of the in vitro synthesis. Thus, we are not persuaded, without
further evidence, that those of skill in the art would not have had a
reasonable expectation of success in substituting the E. coli extracts taught
in Roof for the E. coli extracts taught in Genentech to achieve in vitro
protein synthesis as claimed.
Appellants argue that, according to Roof, SlyD gene mutants of some
E. coli strains grow more slowly than native E. coli strains (App. Br. 6),
giving those of skill in the art reservations about using it to make extracts for

3 We do not read Wülfing or Roof as coming to a conclusion about the
ultimate role of slyD polypeptide in protein folding. (See Roof 1040, left
col. (“Ultimately, the interesting questions about SlyD are those posed above
for FKBPs in general. Is SlyD a specialized FKBP or is it involved in
generalized protein folding?”); see Wülfing 2901, left col. (“In summary, it
is suggested that the COOH-terminal party of [slyD] acts as a sensor
modulating the function of the NH2-terminal domain, which may be a
substrate-specific rotamase.”)).

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in vitro synthesis. Appellants speculate that slowed growth indicates that the
cells have problems “in metabolism (for example, energy generation), or in
properly folded (and properly functional) cellular components, such as
proteins or biomolecular complexes, etc., both of which would be expected
to have deleterious effects on protein synthesis.” (App. Br. 6).
Roof teaches that the slowed growth is only seen in two E. coli
strains, strain B and C (see Roof, 1039, left col.), but Appellants claims are
not limited to these specific E. coli strains. Thus, Appellants have not
persuaded us that those of skill in the art would have been discouraged from
using any bacterial extract mutant for the SlyD gene for in vitro synthesis.
Furthermore, Appellants do not cite evidence in support their assertions of
what those of skill in the art would have considered when choosing an
extract. “Argument of counsel cannot take the place of evidence lacking in
the record.” Meitzner v. Mindick, 549 F.2d 775, 782 (CCPA 1977).
Finally, as explained by the Examiner (Ans. 10-11), the claimed system uses
a cellular extract, not growing cells. Appellants have failed to persuade us
that those of skill in the art would not have expected the extract from SlyD
mutant bacteria to support in vitro synthesis, regardless of how slow or fast
the cells grow. Thus, we are not persuaded by Appellants’ arguments.
Appellants argue that neither Wülfing, Roof, nor Adams is directed to
in vitro synthesis, and that while Genentech discusses in vitro synthesis, it
does not use SlyD mutant bacteria. Thus, Appellants ask: “How could one
skilled in the art have known, based on teachings of Wülfing that a mutant
SlyD would be useful for efficient transcription and translation of genes
(IVTT)?” (Reply Br. 3). “Only a reasonable expectation of success, not
absolute predictability, is necessary for a conclusion of obviousness.” In re
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Longi, 759 F.2d 887, 897 (Fed. Cir. 1985). Genentech teaches an in vitro
system using E. coli. Appellants have failed to persuade us that those in the
art would not have reasonably expected cellular extracts from SlyD mutant
of E. coli would work in an in vitro synthesis system such as taught in
Genentech.
Finally, Appellants argue that the combination of the cited references
does not teach that binding of the SlyD polypeptide to biarsenical reagents.
(Reply Br. 3-4). Appellants question that because “the combined disclosures
of Genentech, Inc., Wülfing et al., Roof et al., and Adams et al. do not teach
the SlyD mutants outlined in the instant specification, how could one skilled
in the art have known that mutant SlyD would not bind to bi-arsenical
reagents?” (Reply Br. 4). Appellants’ claim 28 recites a cellular extract
having a mutant SlyD gene, “wherein the cellular extract is substantially free
of a SlyD polypeptide that binds to a bi-arsenical reagent.” (FF 1). The
claim is not limited to specific SlyD mutations that eliminate only binding to
biarsenical reagents. Instead, the broadest interpretation of the claim
encompasses the SlyD mutations taught in Roof that prevent the entire
polypeptide from being made. (See FF 2). Thus, the cited references teach
all elements of claim 28.
Claim 9
Findings of Fact
6. Appellants’ claim 9 recites that in vitro synthesis system of
claim 28, further comprising a “Gam protein” as a nuclease inhibitor. (App.
Br. 10, Claims App’x).
7. Chatterjee teaches adding Gam protein to cell extracts to
enhance in vitro synthesis. (Chatterjee ¶ [0038]).
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Analysis
The Examiner rejected claim 9 as being obvious over the combination
of Genentech, Wülfing, Roof, Adams, and Chatterjee. (Ans. 7). Claim 9
depends from claim 28 and includes Gam protein in the in vitro synthesis
system. (FF 6). Chatterjee teaches that adding Gam proteins to cell extracts
enhances in vitro synthesis. (FF 7). Appellants argue only that Chatterjee
does not cure the deficiencies of the prima facie case for the obviousness of
claim 28 over the references Genentech, Wülfing, and Roof. Because we
concluded there is no deficiency in that prima facie case for obviousness,
and we accept the Examiner’s conclusion that those of skill in the art would
have added the Gam protein for enhanced in vitro synthesis, we are not
persuaded that the Examiner erred.
Claim 11
Findings of Fact
8. Appellants’ claim 11 recites the in vitro synthesis system of
Appellants’ claim 28 “further comprising at least one inhibitor of at least one
enzyme that catalyzes hydrolysis of high energy phosphate bonds or
hydrolysis or formation of phosphodiester bonds.” (App. Br. 10, Claims
App’x).
9. Gromet-Elhanan teaches that E. coli contains ATPase enzymes
that catalyze the hydrolysis of ATP. (Gromet-Elhanan abstract).
10. Gromet-Elhanan teaches the ATP hydrolysis inhibitors
oligomycin and DCCD. (Gromet-Elhanan Tables III and IV).
11. Stryer teaches that the high energy phosphate bonds of ATP are
consumed during protein synthesis. (Stryer 647-48).
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Analysis
The Examiner rejected claim 11 as being obvious over the
combination of Genentech, Wülfing, Roof, Adams, Stryer and Gromet-
Elhanan. (Ans. 7-8). Claim 11 depends from claim 28 and includes an
inhibitor of enzymes that catalyze hydrolysis of high energy phosphate
bonds in the in vitro synthesis system. (FF 8). Gromet-Elhanan teaches that
E. coli contains enzymes that catalyze the hydrolysis of ATP (FF 9) and
from Stryer those of skill in the art would have known that ATP is consumed
during protein synthesis (FF 11). Thus, those of skill in the art would have
found it obvious to add an inhibitor of the enzymes found in E. coli, such as
those taught in Gromet-Elhanan (FF 10; see Reply Br. 5), as claimed.
Appellants argue only that Gromet-Elhanan and Stryer do not cure the
deficiencies of the prima facie case for the obviousness of claim 28 over the
references Genentech, Wülfing, and Roof. Because we concluded there is
no deficiency in that prima facie case for obviousness, and we accept the
Examiner’s conclusion that those of skill in the art would have added ATP
hydrolysis enzyme inhibitors to preserve ATP in the E. coli extract, we are
not persuaded that the Examiner erred.
V. CONCLUSIONS OF LAW
Those of skill in the art would have found it obvious to make a
cellular extract from a bacterial cell having a mutant SlyD gene for in vitro
synthesis.
VI. ORDER
Upon consideration of the record and for the reasons given,
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the rejection of claims 4, 6-8, 10, 12-14, 16, 17, and 28-32 under 35
under 35 U.S.C. § 103(a) over Genentech, Wülfing, Roof, and Adams is
AFFIRMED;
the rejection of claim 9 under 35 U.S.C. § 103(a) over Genentech,
Wülfing, Roof, Adams, and Chatterjee is AFFIRMED; and
the rejection of claim 11 under 35 U.S.C. § 103(a) over Genentech,
Wülfing, Roof, Adams, Stryer, and Gromet-Elhanan is AFFIRMED.

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).

AFFIRMED

saw

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