Ex Parte Sorrentino et al

Board of Patent Appeals and Interferences

Jun 2, 2009

09866866 (B.P.A.I. Jun. 2, 2009)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte BRIAN SORRENTINO and JOHN SCHUETZ
__________

Appeal 2009-000923
Application 09/866,866
Technology Center 1600
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Decided1: June 2, 2009
__________

Before TONI R. SCHEINER, DONALD E. ADAMS, 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 claims to an
antibody to a Breast Cancer Resistance Protein (BCRP). We have
jurisdiction under 35 U.S.C. § 6(b). We reverse.

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 2009-0923
Application 09/866,866

Statement of the Case
Background
“[T]he BCRP [Breast Cancer Resistance Protein] gene is expressed at
relatively high levels both in primitive CD34-murine HSCs [human stem
cells] and in SP [side population] cells from the bone marrow” (Spec. 11, ll.
9-11). The Specification notes that “[c]ell sorting for BCRP expression
using appropriate antibodies provides a new strategy for stem cell
purification applicable to cells from different organ sources” (Spec. 12, ll.
30-32).
The Claims
Claims 16, 22-24, and 29-34 are on appeal. We will focus on
independent claim 16, which is representative and reads as follows:

16. An isolated antibody that binds to an extracellular
portion of a Breast Cancer Resistance Protein (BCRP)
selected from the group consisting of human
BCRP_(huBCRP) or murine BCRP (mBCRP); wherein the
extracellular portion of the BCRP is in its natural
conformation; wherein the antibody binds to living MCF-7
or 3T3 cells expressing BCRP on their surface; wherein the
antibody does not bind to living MCF-7 cells that do not
express BCRP on their surface; and wherein the antibody
does not bind to denatured BCRP.

The prior art
The Examiner relies on the following prior art references to show
unpatentability:
Zuk US 4,281,061 Jul. 28, 1981
Ross US 6,313,277 B1 Nov. 6, 2001
Bandman US 6,485,933 B1 Nov. 26, 2002
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Owens et al., The genetic engineering of monoclonal antibodies, 168
J. IMMUNOLOGICAL METHODS 149-165 (1994).

Appellants rely on the following additional evidence

Sarkadi Declaration, October 27, 2003.
Sarkadi Declaration, January 17, 2005

The issues
A. The Examiner rejected claims 16, 22-24 and 29-34 under 35 U.S.C. §
112, second paragraph as being indefinite (Ans. 4).
B. The Examiner rejected claims 16, 22 and 31-34 under 35 U.S.C. §
102(e) as being anticipated by Ross (Ans. 4-5).
C. The Examiner rejected claims 16, 22-24 and 29-34 under 35 U.S.C. §
102(e) as being anticipated by Bandman (Ans. 5-6).
D. The Examiner rejected claims 16, 23, 24, and 29 under 35 U.S.C. §
103(a) as being obvious over Ross and Owens (Ans. 6-7).
E. The Examiner rejected claims 16 and 30 under 35 U.S.C. § 103(a) as
being obvious over either Ross or Bandman in view of Zuk (Ans. 8).
A. 35 U.S.C. § 112, second paragraph
The Examiner rejected claims 16, 22-24 and 29-34 under 35 U.S.C. §
112, second paragraph as being indefinite (Ans. 4).
The Examiner finds that “[r]ecitation of a protein without providing
SEQ ID NO for the protein is indefinite and ambiguous because different
laboratories may have the same name for a different protein” (Ans. 4).
Appellants contend that “[t]he terms ‘huBCRP’ and ‘mBCRP’ are not
indefinite because, reading the specification, one of ordinary skill in the art
knows that these terms correspond to a set of well-defined proteins,
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identified by SEQ ID in the specification. There is no ambiguity in what is
claimed by using the terms huBCRP and mBCRP” (App. Br. 5).
In view of these conflicting positions, we frame the definiteness issue
before us as follows:
Did the Examiner err in finding that the claims are indefinite based
upon the recitation of BCRP without a sequence identification number?
Findings of Fact (FF)
1. Claim 16 recites BCRP and specifically limits the BCRP to
antibodies against the human and murine BCRP extracellular regions (see
Claim 16).
2. The Specification teaches that “[n]ames in the literature of
genes encoding this protein include Bcrp1, Mxr, Abcp and ABCG2 gene”
(Spec. 15, ll. 3-4).
3. The Specification teaches that “‘BCRP’ is meant to include all
of such ATP transport proteins obtained from any mammalian source. The
murine protein is also referred to herein as mBCRP, whereas the human
protein is termed herein, ‘huBCRP’” (Spec. 15, ll. 6-8).
4. The Specification teaches two different nucleic acid and amino
acid sequences for both human and murine BCRP (see Spec. 15, ll. 10-16).
Principles of Law
“The test for definiteness is whether one skilled in the art would
understand the bounds of the claim when read in light of the specification.”
Miles Laboratories, Inc. v. Shandon, Inc., 997 F.2d 870, 875 (Fed. Cir.
1993).
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Claims are in compliance with 35 U.S.C. § 112, second paragraph, if
“the claims, read in light of the specification, reasonably apprise those
skilled in the art and are as precise as the subject matter permits.” Hybritech,
Inc. v. Monoclonal Antibodies, Inc., 802 F.2d 1367, 1385 (Fed. Cir. 1987).
Although “it is entirely proper to use the specification to
interpret what the patentee meant by a word or phrase in the
claim, ... this is not to be confused with adding an
extraneous limitation appearing in the specification, which is
improper. By ‘extraneous,’ we mean a limitation read into a
claim from the specification wholly apart from any need to
interpret ... particular words or phrases in the claim.” E.I. du
Pont de Nemours & Co. v. Phillips Petroleum Co., 849 F.2d
1430, 1433, 7 USPQ2d 1129, 1131 (Fed. Cir.), cert. denied,
488 U.S. 986, 109 S. Ct. 542, 102 L.Ed.2d 572 (1988).

In re Paulsen, 30 F.3d 1475, 1480 (Fed. Cir. 1994).
Analysis
The Examiner fails to explain why simply because multiple
laboratories may have different names for a protein or nucleic acid, the use
of one of those names is indefinite. In this case we are not looking to the
Specification to add an extraneous limitation to the claim; instead, we look
to the Specification to ascertain the meaning of the claim term BCRP as it is
used by the inventor in the context of the entirety of his invention (FF 1-4).
The Specification recognizes multiple names for BCRP, and
harmonizes those different names under the rubric of BCRP (FF 2). The
Specification also clearly defines BCRP, and in particular, defines the
human and murine BCRP molecules (FF 3). This definition clearly excludes
other random proteins which are not ATP transporters from falling within
the scope of the claim (FF 3). The Specification provides two exemplary
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sequences each for the human and murine BCRP (FF 4). “[I]t is entirely
proper to use the specification to interpret what the patentee meant by a
word or phrase in the claim.” In re Paulsen, 30 F.3d at 1480.
Conclusion of Law
The Examiner erred in finding that the claims are indefinite based
upon the recitation of BCRP without a sequence identification number.
We reverse the rejection of claims 16, 22-24 and 29-34 under 35
U.S.C. § 112, second paragraph as being indefinite.
B. 35 U.S.C. § 102(e) over Ross
The Examiner rejected claims 16, 22 and 31-34 under 35 U.S.C. §
102(e) as being anticipated by Ross (Ans. 4-5).
The Examiner finds that Ross “teaches an isolated polyclonal and
monoclonal antibody that binds to BCRP” (Ans. 4). The Examiner finds
that “[a]lthough the reference is silent about the antibody binding to an
extracellular portion of BCRP or does not bind to denatured BCRP, said
functional limitation would be inherent properties of the referenced
antibody, because the referenced antibody was obtained against the same
antigen as claimed” (Ans. 4).
Appellants contend that “the ‘277 patent does not, in fact, disclose the
actual generation of any antibody, let alone one that would necessarily bind
to an extracellular portion of BCRP and not to denatured BCRP” (App. Br.
10). Appellants contend that “[t]his omission in the ‘277 patent is
significant because there is nothing within the ‘277 patent from which one
skilled in the art could deduce to what portion (if any) of BCRP the
disclosed antibody would bind” (App. Br. 10).
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In view of these conflicting positions, we frame the anticipation issue
before us as follows:
Did the Examiner err in finding that antibodies to BCRP generated
according to the disclosure of Ross would inherently bind “to an
extracellular portion of a Breast Cancer Resistance Protein” where “the
extracellular portion of the BCRP is in its natural conformation”?
Findings of Fact
5. The Specification teaches that “[t]he strategy of using living
cells transduced with the vector increases the probability that the immune
system will detect external huBCRP epitopes in their native configuration,
rather than epitopes that are internally located in the cells, or epitopes only
present in denatured protein” (Spec. 23, ll. 13-16).
6. Ross teaches that a “polyclonal antibody capable of binding to
BCRP can be prepared by immunizing a mammal with a preparation of
BCRP or functional derivative of BCRP. Methods for accomplishing such
immunizations are well known in the art” (Ross, col. 4, ll. 50-54).
7. Ross teaches that “[m]onoclonal antibodies or fragments
thereof can also be employed to assay for the presence or amount or BCRP
in a particular biological sample. Such antibodies can be produced by
immunizing splenocytes with activated BCRP” (Ross, col. 4, ll. 54-57).
8. Dr. Sarkadi states that “I have used an antibody produced in
accordance with the method of U.S. Patent Application Serial No.
09/866,866 (i.e., 5D3) and shown that the interaction of 5D3 with BCRP in
intact cells is dependent upon the actual conformation within the transport
cycle of this multidrug resistance protein” (Sarkadi Dec. 2/22/05 ¶ 7).
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9. Dr. Sarkadi states that “an antibody generated against an N-
terminal intracellular epitope of BCRP (i.e., BXP-21) cannot recognize
BCRP in a living cell. Therefore, this method is essential to producing an
antibody which recognizes an extracellular portion of BCRP in its natural
conformation” (Sarkadi Dec. 2/22/05 ¶ 7).
Principles of Law
“A claim is anticipated only if each and every element as set forth in
the claim is found, either expressly or inherently described, in a single prior
art reference.” Verdegaal Bros. v. Union Oil Co. of California, 814 F.2d
628, 631 (Fed. Cir. 1987). Analysis of whether a claim is patentable over
the prior art under 35 U.S.C. § 102 begins with a determination of the scope
of the claim. We determine the scope of the claims in patent applications
not solely on the basis of the claim language, but upon giving claims their
broadest reasonable construction in light of the specification as it would be
interpreted by one of ordinary skill in the art. In re Am. Acad. of Sci. Tech.
Ctr., 367 F.3d 1359, 1364 (Fed. Cir. 2004). The properly interpreted claim
must then be compared with the prior art.
“If the prior art reference does not expressly set forth a particular
element of the claim, that reference still may anticipate if that element is
‘inherent’ in its disclosure.” In re Robertson, 169 F.3d 743, 745 (Fed. Cir.
1999). “Inherency, however, may not be established by probabilities or
possibilities. The mere fact that a certain thing may result from a given set of
circumstances is not sufficient.” Id. (quoting Continental Can Co. v.
Monsanto Co., 948 F.2d 1264, 1268 (Fed. Cir. 1991)) (internal quotation
marks and citations omitted).
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Analysis
Each of the independent claims requires not only an antibody which
binds to an extracellular portion of a BRCP, but further requires that the
antibody bind the natural conformation of the BCRP and not bind to
denatured BCRP (see Claims 16, 31, 33).
While Ross reasonably teaches an antibody which binds to BCRP (FF
6-7), Ross provides no evidence to suggest that any of the BCRP antibodies
made according to the disclosed method will necessarily bind to the natural
conformation of BCRP and not bind denatured BCRP, as required by the
claims.
Additionally, the Sarkadi Declaration (2/22/05) states, without
evidentiary contradiction by the Examiner, that “interaction of 5D3 with
BCRP in intact cells is dependent upon the actual conformation within the
transport cycle of this multidrug resistance protein” (Sarkadi Dec. 2/22/05 ¶
7; FF 8).
We do not disagree with the Examiner that synthesis of either
polyclonal or monoclonal antibodies is routine, or that there would not be a
reasonable expectation of obtaining BCRP antibodies using the BCRP
protein. However, the claims do not require simply obtaining antibodies, the
claims require particular specificities in the antibodies for the natural
conformation and not a denatured conformation, specificities which may be
possible, but “[i]nherency, however, may not be established by probabilities
or possibilities. The mere fact that a certain thing may result from a given set
of circumstances is not sufficient.” In re Robertson, 169 F.3d 743, 745 (Fed.
Cir. 1999).
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Here, the Examiner has not even shown that antibodies to the natural
conformation may result from the disclosure of Ross, much less that the
prophetic suggestion to form antibodies in Ross would result in an antibody
which “necessarily functions in accordance with, or includes, the claimed
limitations.” In re Cruciferous Sprout Litig., 301 F.3d 1343, 1349 (Fed. Cir.
2002).
We are not convinced by the Examiner’s statement that “it was [] well
known in the art that antibodies raised against purified membrane-associated
proteins were used in flow-cytometry or to detect or target in vivo cells
expressing said membrane-associated proteins” (Ans. 14). Not only does the
Examiner present no evidence to support this statement, but even if true, it
does not address the fundamental issue of whether antibodies raised against
BCRP would inherently (that is necessarily function) to bind BCRP in the
natural conformation and not in the denatured conformation. The antibodies
used in flow cytometry might bind to both the natural and denatured
conformations. The Examiner has provided no evidence to support this
inherency.
We also are not persuaded by the Examiner’s reliance upon Ross’s
suggestion that BCRP antibodies can be administered to reduce resistance to
chemotherapeutic drugs (see Ans. 12). Ross never synthesizes an antibody
to BCRP and this speculation by Ross, which represents unclaimed subject
matter, does not demonstrate that BCRP antibodies would necessarily bind
to BCRP in the natural conformation and not bind denatured BCRP.

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Conclusion of Law
The Examiner erred in finding that antibodies to BCRP generated
according to the disclosure of Ross would inherently bind “to an
extracellular portion of a Breast Cancer Resistance Protein” where “the
extracellular portion of the BCRP is in its natural conformation”.
We reverse the rejection of claims 16, 22 and 31-34 under 35 U.S.C. §
102(e) as being anticipated by Ross.
C. 35 U.S.C. § 102(e) over Bandman
The Examiner rejected claims 16, 22-24 and 29-34 under 35 U.S.C. §
102(e) as being anticipated by Bandman (Ans. 5-6).
The Examiner finds that Bandman “teaches an isolated polyclonal and
monoclonal antibody that binds to BCRP (see entire document, Abstract and
column 16, lines 15-30 in particular). US Patent ‘933 further teaches that
said antibody is chimeric or humanized or attached to detectable label (see
overlapping columns 18 and 19)” (Ans. 5).
Appellants contend that “prophetic disclosure of purely hypothetical
antibodies does not support the Examiner's assertion that antibodies
disclosed in the ‘933 patent would necessarily ‘bind[] to an extracellular
portion of a Breast Cancer Resistance Protein (BCRP)’ and/or ‘not bind to
denatured BCRP’ as recited in the instant claims” (App. Br. 14).
In view of these conflicting positions, we frame the anticipation issue
before us as follows:
Did the Examiner err in finding that antibodies to BCRP generated
according to the disclosure of Bandman would inherently bind “to an
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extracellular portion of a Breast Cancer Resistance Protein” where “the
extracellular portion of the BCRP is in its natural conformation”?
Findings of Fact
10. Bandman teaches “[a]ntibodies to BCRP may be generated
using methods that are well known in the art. Such antibodies may include,
but are not limited to, polyclonal, monoclonal, chimeric, single chain, Fab
fragments, and fragments produced by a Fab expression library. Neutralizing
antibodies, (i.e., those which inhibit dimer formation) are especially
preferred for therapeutic use” (Bandman, col. 18, ll. 58-64).
11. Bandman teaches that a “variety of protocols for detecting and
measuring the expression of BCRP, using either polyclonal or monoclonal
antibodies specific for the protein are known in the art. Examples include
enzyme-linked immunosorbent assay (ELISA), radioimmunoassay (RIA),
and fluorescence activated cell sorting (FACS)” (Bandman, col. 16, ll. 16-
21).
12. Bandman teaches monoclonal antibodies to BCRP and chimeric
monoclonal antibodies to BCRP (see Bandman, col. 19, ll. 22-45).
13. Bandman teaches that “[a]ntibodies may also be produced by
inducing in vivo production in the lymphocyte population or by screening
recombinant immunoglobulin libraries or panels of highly specific binding
reagents as disclosed in the literature” (Bandman, col. 19, ll. 46-49).
Analysis
As discussed supra, each of the independent claims requires not only
an antibody which binds to an extracellular portion of a BRCP, but further
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requires that the antibody bind the natural conformation of the BCRP and
not bind to denatured BCRP (see Claims 16, 31, 33).
While Bandman reasonably teaches an antibody which binds to BCRP
(FF 10-13), Bandman provides no teaching to select antibodies which bind
to the natural conformation of the BCRP. Bandman provides no evidence to
suggest that any BCRP antibodies will necessarily bind to the natural
conformation of BCRP and not bind denatured BCRP, as required by the
claims.
As we discussed supra, the Examiner has not even shown that
antibodies to the natural conformation may result from the disclosure of
Bandman, much less that the prophetic suggestion to form antibodies in
Bandman would result in an antibody which “necessarily functions in
accordance with, or includes, the claimed limitations.” In re Cruciferous
Sprout Litig., 301 F.3d 1343, 1349 (Fed. Cir. 2002).
We are not persuaded by the Examiner’s reliance on Bandman’s
suggestion that the antibody may be used in FACS analysis (see Ans. 12-
13). Bandman never synthesizes an antibody to BCRP and this speculation
by Bandman regarding FACS analysis with antibodies which do not yet
exist does not demonstrate that BCRP antibodies would necessarily bind to
BCRP in the natural conformation and not bind denatured BCRP.

Conclusion of Law
The Examiner erred in finding that antibodies to BCRP generated
according to the disclosure of Bandman would inherently bind “to an
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extracellular portion of a Breast Cancer Resistance Protein” where “the
extracellular portion of the BCRP is in its natural conformation”.
We reverse the rejection of claims 16, 22-24 and 29-34 under 35
U.S.C. § 102(e) as being anticipated by Bandman.
D. and E. - 35 U.S.C. § 103(a) rejections
The Examiner rejected claims 16, 23, 24, and 29 under 35 U.S.C. §
103(a) as being obvious over Ross and Owens (Ans. 6-7).
The Examiner rejected claims 16 and 30 under 35 U.S.C. § 103(a) as
being obvious over either Ross or Bandman in view of Zuk (Ans. 8).
We reversed supra the rejection of claims 16, 23, 24, and 29 under 35
U.S.C. § 102(e) as unpatentable over Ross and the rejection of claims 16 and
30 under 35 U.S.C. § 102(e) as unpatentable over Bandman. The Examiner
presents the same arguments regarding inherency for the rejection of claims
16, 23, 24, 29, and 30 under U.S.C. § 103(a). The Examiner does not
provide evidence, suggestion, or reasoning to render obvious BCRP
antibodies which bind to BCRP in the natural conformation but do not bind
denatured BCRP. The additional Zuk and Owens references provide no
guidance to suggest such antibodies.
We reverse the rejection of claims 16, 23, 24, and 29 under 35 U.S.C.
§ 103(a) as being obvious over Ross and Owens. We reverse the rejection of
claims 16 and 30 under 35 U.S.C. § 103(a) as being obvious over either Ross
or Bandman in view of Zuk.
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SUMMARY
In summary, we reverse the rejection of claims 16, 22-24 and 29-34
under 35 U.S.C. § 112, second paragraph as being indefinite.
We reverse the rejection of claims 16, 22 and 31-34 under 35 U.S.C. §
102(e) as being anticipated by Ross.
We reverse the rejection of claims 16, 22-24 and 29-34 under 35
U.S.C. § 102(e) as being anticipated by Bandman.
We reverse the rejection of claims 16, 23, 24, and 29 under 35 U.S.C.
§ 103(a) as being obvious over Ross and Owens. We reverse the rejection of
claims 16 and 30 under 35 U.S.C. § 103(a) as being obvious over either Ross
or Bandman in view of Zuk.

REVERSED

Ssc:

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