Ex Parte Karatzas et al

Board of Patent Appeals and Interferences

Jan 5, 2012

10326892 (B.P.A.I. Jan. 5, 2012)

UNITED STATES PATENT AND TRADEMARK OFFICE
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O. Box 1450
Alexandria, Virginia 22313-1450
www.uspto.gov
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
10/326,892 12/20/2002 Costas N. Karatzas 4214/1M196US1 3791
7590 01/05/2012
Elliot M. Olstein
Carella, Byrne, Bain, Gifillan, Cecchi, Stewart &
5 Becker Farm Raod, 2nd Floor
Roseland, NJ 07068
EXAMINER
BERTOGLIO, VALARIE E
ART UNIT PAPER NUMBER
1632
MAIL DATE DELIVERY MODE
01/05/2012 PAPER
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte COSTAS N. KARATZAS,
YUE-JIN HUANG, and ANTHOULA LAZARIS
__________

Appeal 2011-007943
Application 10/326,892
Technology Center 1600
__________

Before DEMETRA J. MILLS, MELANIE L. McCOLLUM, and
STEPHEN WALSH, Administrative Patent Judges.

Opinion for the Board filed by Administrative Patent Judge WALSH.

Opinion dissenting-in-part filed by Administrative Patent Judge
McCOLLUM.

WALSH, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims to a
method for producing a butyrylcholinesterase (BChE) enzyme. The Patent
Examiner rejected the claims as anticipated and obvious. We have
jurisdiction under 35 U.S.C. § 6(b). We affirm.
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STATEMENT OF THE CASE
Claims 40-42, 66-70, 72-75, and 79-81 are on appeal. Claims 40 and
66 are representative and read as follows:
40. A method for producing a BChE enzyme, which method comprises:
a. inducing or maintaining lactation of a transgenic mammal, the
genome of which comprises a DNA sequence encoding a BChE enzyme,
operably linked to a mammary gland-specific promoter, wherein the
sequence further comprises a signal sequence that provides secretion of the
BChE enzyme into the milk of the mammal, whereupon said inducing or
said maintaining of lactation in said transgenic mammal, BChE enzyme is
secreted into the milk of said mammal; and
b. extracting milk from the lactating mammal.

66. The method of Claim 40 wherein said promoter is selected from the
group consisting of the whey acidic protein promoter, the αS1-casein
promoter, the αS2-casein promoter, the β-casein promoter, the κ-casein
promoter, the β-lactoglobin promoter, and the αa-lactalbumin promoter.

The Examiner rejected the claims as follows:
• claims 40-42 and 68-70 under 35 U.S.C. §102(e) as anticipated by
Soreq;1
• claims 66, 67, 72-75, and 79-81under 35 U.S.C. §103(a) as
unpatentable over Soreq in view of Velander;2
• claims 40-42, 66-70, 72-75, and 79-81 under 35 U.S.C. § 103(a) as
unpatentable over DeBoer,3 or Clark, 4 or Lubon5 in view of Wei.6

1 Hermona Soreq et al., US 6,987,211 B1, issued Jan. 17, 2006, Application
filed May 12, 1999.
2 William H. Velander et al., US 6,344,596 B1, issued Feb. 5, 2002.
3 Herman A. DeBoer et al., US 5,633,076, issued May 27, 1997.
4 Anthony J. Clark et al., US 5,322,775, issued June 21, 1994.
5 Henryk Lubon et al., US 5,831,141, issued Nov. 3, 1998.
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ANTICIPATION
The Issue
The Examiner found:
Soreq teaches production of recombinant BChE in the milk of a
mammal by expressing BChE from a transgene encoding BChE
operably linked to a CMV promoter. The use of a mammary specific
promoter in place of the ubiquitously active CMV promoter is
supported by recitation in claim 4 of Soreq. The BChE, a naturally
secreted enzyme, is secreted into the milk of transgenic mice which is
the result of an encoded secretory signal. Soreq also teaches
application of the method to other mammalian species, including
goats (see claim 6 and 7).

(Ans. 4.)
Appellants contend that (1) Soreq is not prior art, (2) the only passage
in Soreq where a mammary gland-specific promoter is mentioned
specifically is Claim 4, and (3) “[n]one of the claims in the originally filed
application define a mammary gland-specific promoter for expressing
butyrylcholinesterase.” (App. Br. 3-4.) Appellants provide a review of
Soreq’s disclosure, citing columns and lines said to support Appellants’
contentions that Soreq (i) did “not disclose expressing BChE enzyme under
the control of a mammary gland-specific promoter” (id. at 4-7); and (ii) did
not “provide any guidance as to which cell-specific promoters may be used
for expressing cholinesterase in a transgenic animal” (id. at 7-8). Further,
Appellants contend that “Soreq does not enable one of ordinary skill in the
art to practice the claimed invention . . . .” (id. at 8-9).

6 Wan-Li Wei et al., High-Level Expression of Human Butyrylcholinesterase
Gene in Bombyx mori and Biochemical-Pharmacological Characteristic
Study of Its Product, 60 BIOCHEM. PHARM. 121-126 (2000).
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The Examiner disagreed with Appellants’ reading of Soreq’s
Specification. (Ans. 8-9.) The Examiner found, for example, that Soreq’s
teaching to use cell specific promoters “clearly intended to encompass the
use of any promoter with a desired cell-specific activity.” (Id. at 8.)
According to the Examiner, Soreq discussed expression in the mammary
gland and its usefulness (id.), and the Specification need not disclose what is
well-known to those skilled in the art (id. at 9).
The issue is whether Appellants have established that Soreq did not
describe expressing BChE from a transgene encoding BChE operably linked
to a mammary gland specific promoter.
Findings of Fact
1. The Examiner’s anticipation findings may be found at Ans. 4 and 8-9.
2. Soreq described methods using transgenic mammals to produce
human acetylcholinesterase or butyrylcholinestersae in their
mammary glands. (Soreq, Example 10, cols. 53ff.)
3. Soreq taught:
the promoters used . . . to control transcription of the AChE encoding
sequences, may also be any of the well-known eukaryotic host cell-
compatible promoters (e.g. animal virus, yeast, mammalian
promoters). The preferred promoters are the CMV, CMV-like, human
AChE and human AChE-like promoters having similar transcription
factor binding sites within the promoter region sequence.

(Id. at col. 8, ll. 35-42.)
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4. Soreq taught: “Features that limit expression to particular cell types
can also be included. Such features include, for example, promoter
and regulatory elements that are specific for the cell type.” (Id. at col.
9, ll. 58-61.)
5. Soreq’s claim 4 reads: “[t]he transgenic non-human mammal of claim
1, wherein the transgenic non-human mammal is female and wherein
said promoter is a mammary gland specific promoter.” (Id. at col.
98.)
6. Appellants provided a copy of the originally filed claims in Soreq’s
Application No. 09/310,638. (App. Br. 14ff, Evidence Appendix.)
Principles of Law
Section 102 provides:
A person shall be entitled to a patent unless . . .
(e) the invention was described in . . . (2) a patent granted on an
application for patent by another filed in the United States before the
invention by the applicant for patent . . . .

“To anticipate a claim, a prior art reference must disclose every
limitation of the claimed invention, either explicitly or inherently.” In re
Schreiber, 128 F.3d 1473, 1477 (Fed. Cir. 1997) (citations omitted).
To anticipate, the description of the invention in the reference must be
“sufficient to put the public in possession of the invention.” In re LeGrice,
301 F.2d 929, 933 (CCPA 1962). The question is “whether one skilled in
the art to which the invention pertains could take the description of the
invention in the printed publication and combine it with his own knowledge
of the particular art and from this combination be put in possession of the
invention on which a patent is sought.” LeGrice , 301 F.2d at 939. “In
particular, one must be able to make the claimed invention without undue
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experimentation.” In re Elsner, 381 F.3d 1125, 1128 (Fed. Cir. 2004)). The
test for anticipation “is not an ‘ipsissimis verbis’ test.” In re Bond, 910 F.2d
831, 832 (Fed. Cir. 1990).
“A patent shall be presumed valid.” 35 U.S.C. § 282.
The test for determining compliance with the written description
requirement is whether the disclosure of the application as originally
filed reasonably conveys to the artisan that the inventor had
possession at that time of the later claimed subject matter, rather than
the presence or absence of literal support in the specification for the
claim language.

In re Kaslow, 707 F.2d 1366, 1375 (Fed. Cir. 1983).
In patent prosecution the examiner is entitled to reject application
claims as anticipated by a prior art patent without conducting an
inquiry into whether or not that patent is enabled or whether or not it
is the claimed material (as opposed to the unclaimed disclosures) in
that patent that are at issue. In re Sasse, 629 F.2d 675, 681, 207
USPQ 107, 111 (C.C.P.A.1980) (“[W]hen the PTO cited a disclosure
which expressly anticipated the present invention ... the burden was
shifted to the applicant. He had to rebut the presumption of the
operability of [the prior art patent] by a preponderance of the
evidence.” (citation omitted)). The applicant, however, can then
overcome that rejection by proving that the relevant disclosures of the
prior art patent are not enabled.

Amgen Inc. v. Hoechst Marion Roussel, Inc., 314 F.3d 1313, 1355 (Fed. Cir.
2003).
Analysis
It is undisputed that Soreq disclosed a method of producing
recombinant BChE in the milk of a mammal comprising expressing BChE
from a transgene encoding BChE operably linked to a CMV promoter,
inducing lactation, and extracting milk.
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Appellants’ first argument is that Soreq is not prior art because
Soreq’s original claims did not recite a mammary gland-specific promoter.
(App. Br. 4.) It is undisputed that “a mammary gland-specific promoter”
was not in the original claims, but this fact, taken alone, is insufficient to
obviate the rejection because § 102 does not require that anticipating subject
matter be found in an original claim.
Appellants next argue that, apart from claim 4, Soreq’s Specification
did not disclose a mammary gland-specific promoter. (App. Br. 4-5.)
Appellants acknowledge Soreq’s disclosures of cholinesterase expression in
a transgenic animal and that promoters specific for a desired cell type may
be used. (Id. at 7.) However, Appellants assert that Soreq did not “provide
guidance as to which cell-specific promoters may be used for expressing
cholinesterase in a transgenic animal,” i.e., a mammary gland-specific
promoter. (Id. at 7-8.) Here, Appellants highlight the lack of literal
antecedent basis for the mammary gland-specific promoter recited in claim
4. The Examiner responded first by noting the presumed validity of the
Soreq patent, and then with an analysis of Soreq’s disclosure. (Ans. 8-9.)
The Examiner is correct that we begin with a presumption that the
Soreq patent is valid. 35 U.S.C. § 282. Appellants therefore have the
burden of persuasion to show that Soreq’s claim 4 is invalid. Appellants’
theory of invalidity seems to assume claim 4 contains “prohibited new
matter,” but neither Appellants nor the Examiner use that term. The
statutory presumption is that claim 4 does not contain prohibited new matter.
Appellants’ evidence and arguments demonstrate a lack of literal antecedent
basis. However, this evidence, without more, is insufficient to establish that
claim 4 contains prohibited new matter because literal antecedent basis is not
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required for a claim to be supported by the written description portion of a
Specification. See Kaslow, 707 F.2d 1366, 1375; see also Bond, 910 F.2d at
832.
Appellants further argue that “Soreq does not enable one of ordinary
skill in the art to practice the claimed invention….” (App. Br. 8-9.) We are
not persuaded by this argument as Appellants have not satisfied their burden
of proving that Soreq did not enable expression via a DNA sequence
encoding a BChE enzyme, operably linked to a mammary gland-specific
promoter. See Amgen, 314 F.3d at 1355. Satisfying this burden requires
more than identifying the absence of literal antecedent basis for the subject
matter in Soreq’s claim 4 because enablement is assessed by weighing a
number of factors. See In re Wands, 858 F.2d 731, 737 (Fed. Cir. 1988).
For example, Appellants have not considered the state of the prior art and
the relative skill of those in the art. (Id.) For example, the element that
Appellants assert was missing from Soreq’s Specification, as originally filed,
was already known by skilled artisans. (Ans. 5.)
Claims 41, 42, and 68-70 have not been argued separately and
therefore stand or fall with claim 40. 37 C.F.R. § 41.37(c)(1)(vii).

OBVIOUSNESS
Principles of Law
“The combination of familiar elements according to known methods
is likely to be obvious when it does no more than yield predictable results.”
KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007). “If a person of
ordinary skill can implement a predictable variation, § 103 likely bars its
patentability.” Id. at 417.
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I. The Rejection over Soreq and Velander
In addition to the findings made regarding Soreq in the anticipation
rejection, the Examiner further found that Soreq did not identify the
mammary gland specific promoters WAP, α, β, κ-casein,
β-lactoglobin promoter, and α-albumin promoter, recited in Appellants’
claims 66, 67, 72-75, and 79-81. (Ans. 5.) However, the Examiner found
that Velander taught expressing human factor IX in the milk of non-human
transgenic mammals using mammary gland specific promoters, including
WAP, α, β, κ-casein, β-lactoglobin promoter, and α-albumin promoter. (Id.)
According to the Examiner, it would have been obvious to a person of
ordinary skill in the art at the time the invention was made to use a
mammary gland specific promoter such as β-casein promoter in Soreq’s
method with a reasonable expectation of successfully producing BChE in the
milk of non-human mammals based upon the combined teachings of Soreq
and Velander. (Id.) We agree with the Examiner’s findings and conclude
that the rejection established a prima facie case of obviousness.
Appellants again contend that Soreq is not prior art. (App. Br. 9.)
Alternatively, Appellants assert that if Soreq is prior art it “merely
provide[d] a broad generic description of promoters which may be specific
for desired cell types.” (Id.) According to Appellants, the combination of
Soreq and Velander does not render the claimed invention obvious because
neither reference suggests “that DNA encoding [BChE] may be expressed in
a transgenic animal under the control of a mammary gland-specific
promoter.” (App. Br. 10.)
Appellants have not provided authority or persuasive evidence
establishing that the entire disclosure, including a later added claim, of a US
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patent having an earlier effective US filing date could not be relied upon to
reject the current application claims. Even if Appellants were to establish
that the subject matter in Soreq’s claim 4 is not prior art, the remainder of
Soreq’s disclosure would still be prior art.
Appellants argue that “Soreq, if prior art, at best merely provides a
broad generic description of promoters which may be specific for desired
cell types.” (App. Br. 9.) This argument is unpersuasive because Soreq’s
instructions to express proteins in the milk of transgenic animals, and to use
a promoter specific for a desired cell type, must be considered with
Velander’s teachings. Each reference “must be read, not in isolation, but for
what it fairly teaches in combination with the prior art as a whole.” In re
Merck & Co., Inc., 800 F.2d 1091, 1097 (Fed. Cir. 1986) (citation omitted).
Thus, Appellants’ contention that neither Soreq or Velander suggests “that
DNA encoding [BChE] may be expressed in a transgenic animal under the
control of a mammary gland-specific promoter” (id. at 10) is also
unpersuasive because it fails to address the prior art as a whole.
Velander evidenced that particular mammary gland-specific
promoters were known for the expression of a gene in mammary tissue and
in the milk of non-human transgenic mammals. (Ans. at 5, 9.) These
findings are supported by the evidence and are sufficient to support the
Examiner’s conclusion that a skilled artisan would have found it obvious to
combine these teachings and select one of Velander’s mammary gland-
specific promoters as the promoter specific for a desired cell type in Soreq’s
method, e.g., the mammary gland cells in Soreq’s method. (Ans. 5.) We
agree with the Examiner that following the combined instructions to
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substitute a Velander promoter into Soreq’s method would have been prima
facie obvious.
Claims 67, 72-75, and 79-81 have not been argued separately and
therefore stand or fall with claim 66. 37 C.F.R. § 41.37(c)(1)(vii).
II. The Rejection over any of DeBoer, Clark, or Lubon, in view of Wei
The Examiner’s position is that “Wei taught the expression of
recombinant BChE and the utility of mass producing BChE for
pharmaceutical use.” (Ans. 7.) According to the Examiner, each of DeBoer,
Clark, or Lubon taught producing a transgenic protein in milk using a
transgene operably linked to a mammary gland specific promoter. (Id. at 6-
7.) According to the Examiner, it would have been obvious to replace the
various genes of DeBoer, Clark, or Lubon with Wei’s BChE gene because
expression of a transgene in the mammary gland was an art accepted means
of producing large quantities of recombinant proteins. (Id.)
The Examiner found that a skilled artisan would have been motivated
to produce large quantities of BChE for use in therapy because Wei taught
that recombinant human BChE is pharmaceutically useful. (Id.) Further, the
Examiner found that the skilled artisan would have had a reasonable
expectation of successfully combining DeBoer, Clark, or Lubon with Wei
because it was routine in the art to express a recombinant gene in the
mammary epithelia cells of mammals and a vast array of genes had been
utilized and expressed successfully. (Id.)
Appellants contend that neither DeBoer, Clark, nor Lubon disclosed
or suggest “the expression of BChE enzyme using a mammary gland-
specific promoter.” (Id. at 10.) Appellants also assert that “Wei is directed
solely to expressing human BChE in silkworms,” and therefore does not
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suggest the claimed invention. (Id.) According to Appellants, “the cited
references, taken alone or in combination, provides no basis for one of
ordinary skill in the art to express a BChE enzyme under the control of a
mammary gland-specific promoter.” (Id. at 10-11.) We disagree.
First, contrary to Appellants’ contention, Wei was not directed
“solely” to expressing human BChE in silkworms as a purposeless exercise.
The Examiner found that Wei described the potential pharmaceutical
importance of BChE, thus providing a sufficient evidentiary basis for finding
that a person of ordinary skill in the art would have been motivated to
produce recombinant BChE. Appellants have not shown this finding was
mistaken. Second, as evidenced by each of DeBoer, Clark, or Lubon,
“expression of a transgene in the mammary gland was an art accepted means
of producing large quantities of recombinant proteins.” (Ans. 7.)
Appellants make no attempt to dispute that fact. We conclude that the
rejection’s evidence supports the prima facie case of obviousness, that
Appellants’ arguments are insufficient to establish error, and that the
evidence viewed as a whole compels affirmance.
Claims 40-42, 66-70, 72-75, and 79-81 have not been argued
separately and therefore stand or fall with claim 40. 37 C.F.R.
§ 41.37(c)(1)(vii).
CONCLUSIONS OF LAW
Appellants have not met the burden of showing that Soreq did not
describe a method expressing BChE from a transgene encoding BChE
operably linked to a mammary gland specific promoter.
The record supports the Examiner’s conclusion that the combination
of Soreq and Velander would have suggested to a skilled artisan a method of
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expressing DNA encoding BChE in a transgenic animal under the control of
a promoter listed in claim 66.
The record supports the Examiner’s conclusion that the combination
of any of DeBoer, Clark, or Lubon, with Wei would have suggested to a
skilled artisan a method of expressing DNA encoding BChE under the
control of a mammary gland-specific promoter.
SUMMARY
We affirm the rejection of claims 40-42 and 68-70 under 35 U.S.C.
§102(b) as anticipated by Soreq;
we affirm the rejection of claims 66, 67, 72-75, and 79-81
under 35 U.S.C. §103(a) as unpatentable over Soreq in view of Velander;
we affirm the rejection of claims 40-42, 66-70, 72-75, and
79-81 under 35 U.S.C. § 103(a) as unpatentable over any of DeBoer, Clark,
or Lubon, in view of Wei.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).

AFFIRMED

lp
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McCOLLUM, Administrative Patent Judge, dissenting-in-part.

I disagree with my colleagues that the anticipation rejection over
Soreq should be affirmed. In finding that Soreq anticipates present claim 40,
the Examiner relies on claim 4 of Soreq (Ans. 4). However, it is undisputed
that claim 4 was not in the Soreq application as originally filed (App. Br. 3-
4). In addition, the Examiner has not otherwise shown that Soreq anticipates
present claim 40. Thus, I would reverse the rejection under 35 U.S.C.
§ 102(e) over Soreq.
However, I concur with my colleagues as to their decision to affirm
the obviousness rejections.

DISSENTING-IN-PART