Ex Parte Bae

Board of Patent Appeals and Interferences

Apr 5, 2010

10884862 (B.P.A.I. Apr. 5, 2010)

UNITED STATES PATENT AND TRADEMARK OFFICE
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BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
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Ex parte JOO-EUN BAE
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Appeal 2009-013469
Application 10/884,862
Technology Center 1600
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Decided: April 5, 2010
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Before LORA M. GREEN, 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 claims to a
leukemic antigen. We have jurisdiction under 35 U.S.C. § 6(b). We reverse.
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Statement of the Case
Background
“CD19, a 95 kDa B lineage-specific transmembrane glycoprotein,
functions as a central response regulator in B cells and offers many unique
characteristics that make it a relevant target for developing
immunotherapeutic strategies” (Spec. 2 ¶ 0004).
The Claims
Claims 1-5, 21, and 31-33 are on appeal. Claims 1 and 31 are
representative and read as follows:
1. An isolated leukemic antigen consisting of a fragment
of CD19 (SEQ ID NO: 13) or a variant thereof having one,
two, or three conservative or non-conservative amino acid
substitutions that is capable of stimulating a cytotoxic T-
lymphocyte reaction against a cell expressing CD 19,
wherein the fragment is
(a) 11 to 80 amino acids in length or
(b) 9 to 80 amino acids in length and comprises the
amino acid sequence RLLFFLLFL (SEQ ID NO: 1),
TLAYLIFCL (SEQ ID NO: 2), LLFLTPMEV (SEQ ID NO:
3), KLMSPKLYV (SEQ ID NO: 4), or LLFFLLFLV (SEQ
ID NO: 5).

31. An isolated leukemic antigen consisting of a fragment
of CD19 (SEQ ID NO: 13) or a variant thereof, wherein the
variant has one or two conservative or non-conservative
amino acid substitutions, wherein the fragment or variant is
immunologically recognized by MHC restricted T-
lymphocytes that are HLA-A2.1 restricted and is capable of
stimulating a cytotoxic T-lymphocyte reaction against cells
expressing CD 19, and wherein the fragment or variant
thereof is
(a) 11 to 40 amino acids in length and comprises two
anchor amino acids, wherein the anchor amino acids
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comprise a leucine or isoleucine residue separated from a
valine residue by six amino acids; or
(b) 9 to 40 amino acids in length and comprises the
amino acid sequence RLLFFLLFL (SEQ ID NO: 1),
TLAYLIFCL (SEQ ID NO: 2), LLFLTPMEV (SEQ ID NO:
3), KLMSPKLYV (SEQ ID NO: 4), or LLFFLLFLV (SEQ
ID NO: 5).

The prior art
The Examiner relies on the following prior art references to show
unpatentability:
Leung US 6,440,386 B1 Aug. 27, 2002

Nestle et al., Human Sunlight-Induced Basal-Cell-Carcinoma-
Associated Dendritic Cells Are Deficient in T Cell Co-Stimulatory Molecules
and Are Impaired as Antigen-Presenting Cells, 150 AM. J. PATHOLOGY 641-
651 (1997).

The issues
A. The Examiner rejected claims 1-5, 21, and 31-33 under 35 U.S.C.
§ 112, first paragraph, as failing to comply with the written description
requirement (Ans. 3-7).
B. The Examiner rejected claims 1, 2, and 21 under 35 U.S.C. § 102(a)
and § 102(e) as anticipated by Leung (Ans. 7-8).
C. The Examiner rejected claims 1 and 5 under 35 U.S.C. § 103(a) as
obvious over Leung and Nestle (Ans. 8-10).
A. 35 U.S.C. § 112, first paragraph, written description
The Examiner finds that the “specification provides no teaching on
any other fragments or variants of CD19 in length between 9-80 comprising
or not comprising SEQ ID NO: 1 or 2 that could bind to MHC HLA-A2.1
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restricted T cells and stimulate a cytotoxic T-lymphocyte reaction” (Ans. 4).
The Examiner finds that “[t]hus, the claims encompass peptides that are
significant structural and functional dissimilarity and diversity as compared
to SEQ ID NO: 1 and 2” (Ans. 4).
Appellant argues that the “Examiner’s reasoning contains several
errors: first, the claims are construed over broadly; second, the law of
written description has been misapplied; third, the specification describes an
adequate number of representative species; and fourth, structural
characteristics of the claimed leukemic antigens are correlated to a known
function in the specification” (App. Br. 8).
In view of these conflicting positions, we frame the written
description issue before us as follows:
Does the evidence of record support the Examiner’s conclusion that
the Specification does not provide an adequate written description of the
isolated leukemic antigen fragment of Claim 1?
Findings of Fact (FF)
1. The Specification teaches the complete sequence of SEQ ID
NO: 13 (see Seq. Listing, SEQ ID NO: 13).
2. The Specification teaches that a “total of 556 amino acids of
CD19 protein, listed above as SEQ ID NO: 13, were retrieved from the
SWISS-PROT databank and analyzed for HLA-A2.1 binding epitopes as
nonamers by the peptide motif search software SYFPEITHI” (Spec. 38 ¶
0105).
3. The Specification teaches 180 different 9 mer peptide fragments
that were identified by the peptide search software (see Spec. 38-43 ¶ 0105).
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4. The Specification teaches five peptides selected from SEQ ID
NO: 13 which were tested for binding to HLA (see Spec. 48 ¶ 0109-0111)
5. The Specification teaches that “the peptides of SEQ ID NOS: 2,
3, 4, and 6 gave good and prolonged stable binding. Several other peptides
provided good initial binding over baseline values” (Spec. 48 ¶ 0112).
Peptides 3 and 4 were derived from C19; peptide 6 from C20 (id.).
6. The specification teaches an MHC peptide binding assay which
measures “peptide binding to HLA-A2.1” (Spec. 50 ¶ 0117).
Principles of Law
The first paragraph of 35 U.S.C. § 112 “requires a ‘written description
of the invention’ which is separate and distinct from the enablement
requirement.” Vas-Cath Inc. v. Mahurkar, 935 F.2d 1555, 1563 (Fed. Cir.
1991). An adequate written description of a chemical invention “requires a
precise definition, such as by structure, formula, chemical name, or physical
properties.” University of Rochester v. G.D. Searle & Co., Inc., 358 F.3d
916, 927 (Fed. Cir. 2004); Regents of the Univ. of Cal. v. Eli Lilly & Co.,
Inc., 119 F.3d 1559, 1566 (Fed. Cir. 1997); Fiers v. Revel, 984 F.2d 1164,
1171 (Fed. Cir. 1993).
“A description of what a material does, rather than of what it is,
usually does not suffice.” Rochester, 358 F.3d at 923; Eli Lilly, 119 F.3d at
1568. Instead, the “disclosure must allow one skilled in the art to visualize or
recognize the identity of the subject matter purportedly described.” Id.
In addition, possession of a genus “may be achieved by means of a
recitation of a representative number of [compounds] … falling within the
scope of the genus.” Eli Lilly, 119 F.3d at 1569. “Possession may not be
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shown by merely describing how to obtain possession of members of the
claimed genus.” Ex parte Kubin, 83 USPQ2d 1410, 1417 (BPAI 2007)
(citing Rochester, 358 F.3d at 927).
Analysis
The Examiner’s rejection appears to be predicated on the argument
that “although the entire structural detail of claimed product comprising
biological macromolecule may not be spelled out and actual reduction to
practice may be absent, the critical element responsible for claimed activity,
here, the binding motif for HLA-A2.1 restricted T-cell, should be present in
order to correlate claimed products with claimed function” (Ans. 13).
However, part (a) of the instant claims provide a specific definition,
by structure and formula, for the claimed polypeptides, which must consist
of a fragment 11 to 80 amino acids in length from SEQ ID NO: 13 (CD19)
and have no more than three conservative or non-conservative amino acid
substitutions (see, e.g., Claim 1). The Specification describes the CD19
protein and modes of identifying peptides therein (FF 1-2), including
providing 180 examples of peptides which fall within the scope of the claims
(FF 3), and testing the activity of five peptides in functional assays (FF 4-6).
In Falko-Gunter, the Federal Circuit found that:
[A] requirement that patentees recite known DNA
structures, if one existed, would serve no goal of the written
description requirement. It would neither enforce the quid
pro quo between the patentee and the public by forcing the
disclosure of new information, nor would it be necessary to
demonstrate to a person of ordinary skill in the art that the
patentee was in possession of the claimed invention.

Falko-Gunter Falkner v. Inglis, 448 F.3d 1357, 1368 (Fed. Cir. 2006).
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Consistent with Falko-Gunter, Appellant correctly noted that “[o]ne of skill
in the art could readily envision all of the amino acid sequences that are
fragments or variants of SEQ 1D NO: 13. With the aid of a computer, it is
possible to list the sequences of all of the fragments and variants of SEQ ID
NO: 13 that fall within the scope of the claimed genus” (App. Br. 10).
We find that Appellant has the better position. In this particular fact
pattern, while the genus is very large, it would have been feasible for
Appellant to program a computer to list all of the species and submit this list
in a table with the Specification, providing express support for each species.
In Falko-Gunter, the Federal Circuit clearly indicated that adequate written
description does not require reciting known structures simply as a formality.
Falko-Gunter, 448 F.3d at 1368.
The Examiner also argues that the skilled artisan “would not be
convinced and [the] application does not provide any evidence [] that any
fragment with less than 80 amino acids located anywhere [within the] 556
amino acids of the CD19 molecule [would have the] ability of binding to the
HLA-A2.1 restricted T cell and induce[] cytotoxic response” (Ans. 20).
The Examiner has provided no reason or evidence to support the
conclusion that the skilled artisan would conclude that the claimed genus of
peptides will not be “capable of stimulating a cytotoxic T-lymphocyte
reaction against a cell expressing CD19” as required by Claim 1.
Appellant, however, has provided evidence to suggest that a
representative number of species will have the required function. The
Specification expressly states that the SYFPEITHI program is capable of
analyzing peptides for HLA-A2.1 binding epitopes and identifies 180 such
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peptides (FF 2-3). Appellant also cites Gomez-Nunez1 in the Evidence
Appendix, who teaches that “[w]e have compared the data of three
sequence-based methods with the in vitro binding to HLA-A*0201
molecules on live cells. Our results confirm that these algorithms predict
peptide/MHC interaction well” (Gomez-Nunez 1297, col. 2).
Appellant also has other evidence present in paragraph 0111 of the
Specification, which shows that SEQ ID NOS: 2, 3, and 4 gave good and
stable binding and SEQ ID NOS: 1 and 5 bound less well (FF 4-5). SEQ ID
NOS: 2, 3 are drawn from amino acids 296-312 of the CD19 protein and
SEQ ID NO: 4 is drawn from amino acids 150-159 of the CD19 protein.
SEQ ID NO: 1 is drawn from amino acids 5-14 of the CD19 protein. This
evidence supports the conclusion that peptides drawn from multiple different
regions of CD19 will be capable of stimulating the requires cytotoxic T-
lymphocyte reaction.

Conclusion of Law
The evidence of record does not support the Examiner’s conclusion
that the Specification does not provide an adequate written description of the
isolated leukemic antigen fragment of Claim 1.
B. 35 U.S.C. § 102(b) over Leung
The Examiner finds that Leung et al., disclose a 12 amino acid
fragment of CD19 at position 433-444 of SEQ ID NO: 13 as evidenced by

1 Gomez-Nunez et al., Peptide binding motif predictive algorithms
correspond with experimental binding of leukemia vaccine
candidate peptides to HLA-A*0201 molecules, 30 LEUKEMIA RES.
1293-1298 (2006).
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protein sequence search (provided). Leung et al., disclose that the peptide is
antigenic peptide, which is the binding site of CD19 in the Abl leukemia”
(Ans. 7).
Appellant argues that “Leung does not teach an isolated leukemic
antigen consisting of a fragment of CD19 or a variant thereof. Although
Leung discloses a 12 amino acid sequence of CD19 (SQDGSGYENPED),
this sequence is not an isolated antigen consisting of a fragment of CD19”
(App. Br. 23, footnote omitted).
In view of these conflicting positions, we frame the anticipation issue
before us as follows:
Does the evidence of record support the Examiner’s conclusion that
Leung teaches an antigen consisting of an isolated fragment of CD19 as
required by Claim 1?
Findings of Fact
7. Leung teaches that an “Ab fusion protein containing a
phosphorylation sequence for pTK phosphorylation, when linked to a
corresponding SH2 domain via a flexible peptide hinge, can therefore be
labeled with 32P at the tyrosine” (Leung, col. 7, ll. 18-22).
8. Leung teaches CD19 peptide sequences in Table 1a, which is
reproduced in part below:

Table 1a of Leung shows SH2 domain sequences from a number of proteins
(See Leung, col. 7-8).
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Principles of Law
“[A]nticipation of a claim under § 102 can be found only if the prior
art reference discloses every element of the claim ….” In re King, 801 F.2d
1324, 1326 (Fed. Cir. 1986) (citing Lindemann Maschinenfabrik GMBH v.
American Hoist & Derrick Co., 730 F.2d 1452, 1458 (Fed. Cir. 1984)).
“[A]bsence from the reference of any claimed element negates anticipation.”
Kloster Speedsteel AB v. Crucible, Inc., 793 F.2d 1565, 1571 (Fed. Cir.
1986).
Analysis
There is no dispute that Leung teaches a polypeptide of 12 amino
acids which includes an amino acid sequence that has 100% sequence
identity to CD19 (FF 8). However, Leung does not teach the peptide itself
in “consisting of” form, but rather teaches the inclusion of the peptide
(which is an SH2 domain of CD19) into a fusion protein with peptides from
other, non CD19 proteins (FF 7).
We will address the Examiner’s question of “[i]f claimed peptide is
called ‘isolated’, why could Leung’s peptide not?” (Ans.23). Leung’s CD19
peptide is never physically synthesized as a molecular entity by itself and is
therefore never “isolated” (FF 7). If the word “isolated” was interpreted as
urged by the Examiner, then no naturally occurring “isolated” amino acid
fragment or nucleic acid sequence would ever be patentable since they are
necessarily present in the context of a chromosome in an organism or in a
full length protein in the prior art.
That is, Leung uses the nucleic acid sequences of several different
peptides to form a nucleic acid which is then cloned into an expression
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vector (see Leung, col. 9). This expression vector then will express a fusion
protein which may, with appropriate selection of SH2 domains, comprise a
CD19 peptide, but will not consist of a CD19 peptide because the expressed
fusion protein also has antibody amino acid sequence fused to the CD19
sequence. We are thus compelled to find that Leung does not teach within
the meaning of § 102 an antigen consisting of an isolated fragment of CD19
as required by Claim 1.
Conclusion of Law
The evidence of record does not support the Examiner’s conclusion
that Leung teaches an antigen consisting of a fragment of CD19 as required
by Claim 1.
C. 35 U.S.C. § 103(a) over Leung and Nestle
The Examiner relies upon Nestle to address limitations of the
dependent claims. The Examiner does not rely upon Nestle to teach an
isolated peptide consisting of a CD19 sequence. Therefore, having reversed
the anticipation rejection for the absence of a peptide consisting of the CD19
sequence, we necessarily reverse the obviousness rejection which does not
provide any additional evidence suggesting the peptide required by Claim 1.
SUMMARY
In summary, we reverse the rejection of claims 1-5, 21, and 31-33
under 35 U.S.C. § 112, first paragraph, written description.
We reverse the rejection of claims 1, 2, and 21 under 35 U.S.C. §
102(b) as anticipated by Leung.

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We reverse the rejection of claims 1 and 5 under 35 U.S.C. § 103(a)
as obvious over Leung and Nestle.

REVERSED

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