Ex Parte LI

Board of Patent Appeals and Interferences

Mar 18, 2010

10411284 (B.P.A.I. Mar. 18, 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 YI LI
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Appeal 2009-004709
Application 10/411,284
Technology Center 1600
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Decided: March 18, 2010
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Before JAMES T. MOORE, Vice Chief Administrative Patent Judge, and
RICHARD M. LEBOVITZ and MELANIE L. McCOLLUM, Administrative
Patent Judges.

McCOLLUM, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a protein.
The Examiner has rejected the claims as lacking utility and being
nonenabled. We have jurisdiction under 35 U.S.C. § 6(b). We reverse.

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STATEMENT OF THE CASE
Claims 25-34 are on appeal. Claims 1, 13, 17-20, and 22-24 are also
pending but have been withdrawn from consideration by the Examiner.
(App. Br. 2.) We will focus on claim 25, the only independent claim on
appeal, which reads as follows:
25. An isolated protein comprising a polypeptide having an amino
acid sequence selected from the group consisting of:
(a) amino acid residues 1 to 415 of SEQ ID NO:2; and
(b) the amino acid sequence of the full-length polypeptide encoded
by the cDNA clone contained in ATCC Deposit No. 97334.
The Examiner relies on various references, which are listed on page 3
of the Examiner’s Answer, as providing evidence of unpatentability. Of
these references, we discuss the following:
Tae H. Ji et al., G Protein-coupled Receptors, 273 THE JOURNAL OF
BIOLOGICAL CHEMISTRY 17299-17302 (1998) (hereinafter “Ji”);
Philip M. Murphy et al., International Union of Pharmacology. XXII.
Nomenclature for Chemokine Receptors, 52 PHARMACOLOGICAL REVIEWS
145-176 (2000) (hereinafter “Murphy”); and
Laura Lasagni et al., An Alternatively Spliced Variant of CXCR3
Mediates the Inhibition of Endothelial Cell Growth Induced by IP-10, Mig,
and I-TAC, and Acts as Functional Receptor for Platelet Factor 4, 197 J.
EXP. MED. 1537-1549 (2003) (hereinafter “Lasagni”).
Claims 25-34 stand rejected under 35 U.S.C. § 101 as lacking utility
and under 35 U.S.C. § 112, first paragraph, as being nonenabled based on
the lack of utility (Ans. 4 & 7).
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ISSUE
Does the evidence support the Examiner’s conclusion that the protein
of claim 25 lacks utility?
FINDINGS OF FACT
1. Appellant’s application was filed on April 11, 2003. It claims
the benefit of a provisional patent application filed April 12, 2002, and lists
it as a CIP of 09/101,518, which is a National Stage Application of a PCT
application filed January 11, 1996 (Spec. ¶ [0001]).
2. Ji, which was published in 1998, discloses that G protein-
coupled receptors (GPCRs) “have an extracellular N-terminal segment,
seven [transmembrane domains (TMs)], which form the TM core, three
exoloops, three cytoloops, and a C-terminal segment” (Ji 17299).
3. Ji also discloses that the “N-terminal segments . . . , loops . . . ,
and C-terminal segments . . . vary in size, an indication of their diverse
structures and functions” (id.).
4. Murphy, which was published in 2000, discloses that
“chemokine receptors comprise a large branch of the rhodopsin family of
cell surface, seven-transmembrane domain (7TMD), G protein-coupled
receptors (GPCRs)” (Murphy 146).
5. Murphy also discloses that “[c]hemokine receptors are defined
by their ability to signal on binding one or more members of the chemokine
superfamily of chemotactic cytokines” (id.).
6. In addition, Murphy discloses that the “major shared biological
function [of chemokine receptors] is leukocyte trafficking and dependent
processes such as immune surveillance, innate and adaptive immune
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responses, and various forms of pathological inflammation,” but that,
“[w]ithin this general area, . . . each chemokine receptor appears to have a
specific role, determined by its expression pattern on specific subsets of
leukocytes, and by the temporal and spatial specificity of cognate ligand
expression” (id.).
7. Murphy also discloses that IL8Rβ is a previous name of a
chemokine receptor now known as CXCR2, which is a receptor for the
chemokine IL-8 (id. at 150 & 155).
8. In addition, Murphy discloses that CXCR3 is a different
chemokine receptor having a deduced protein sequence that is about 30%
identical with CXCR2 (id. at 157).
9. Murphy also discloses that “CXCR3 binds three . . . chemokine
agonists, I-TAC, Mig, and IP-10 . . . , all of which chemoattract and induce
calcium flux in activated T cells, tumor-infiltrating lymphocytes, and
CXCR3-transfected cells” (id.).
10. The Specification discloses the polypeptide of SEQ ID NO: 4,
the polypeptide of SEQ ID NO: 2, and a “polypeptide expressed by the
human cDNA contained in ATCC Deposit No. 97334” (Spec. ¶¶ [0011] &
[0013]). Claim 25 recites SEQ ID NO: 2 and the cDNA clone contained in
ATCC Deposit No. 97334, but not SEQ ID NO: 4.
11. The Specification states that “the polypeptides of the present
invention are human 7-transmembrane receptors, which have been putatively
identified as chemokine receptors, sometimes hereinafter referred to as
‘G-Protein Chemokine Receptor’ or ‘HSATU68’” (id. at ¶ [0002]).
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12. The Specification discloses that the “[p]olynucleotides of this
invention were discovered in a human genomic library derived from human
activated T cells,” “are structurally related to the G protein-coupled receptor
family,” and “include polynucleotides having open reading frames encoding
a protein of 415 amino acid residues (SEQ ID NO:2),” which “exhibit[s]
homology at the amino acid level to a human interleukin-8 receptor beta . . .
as shown in Figure 3” (id. at [0045]).
13. The Specification states that the “present invention further
provides antibodies that inhibit or abolish the binding of the G-protein
chemokine receptor ligand (e.g., IFN-gamma-induced monokine-2 (MIG
. . . ); IFN-inducible protein-10 (IP10 . . . ); interferon-inducible T cell-alpha
chemoattractant (ITAC . . .)) to G-protein chemokine receptor expressing
cells” (id. at ¶ [0030]).
14. The Specification also states that “a polypeptide demonstrating
a G-protein Chemokine Receptor ‘functional activity’” refers to “a
polypeptide capable of displaying one or more known functional activities
associated with a full-length (complete) G-protein Chemokine Receptor
protein. Such functional activities include, but are not limited to, biological
activity (e.g., ability to mediate chemotaxis induced by G-protein
Chemokin[e] Receptor ligands (e.g. MIG . . . , IP-10 . . . , or ITAC . . . ).”
(Id. at ¶ [0063].)
15. In addition, the Specification states that, “where a G-protein
Chemokine Receptor ligand is identified (e.g., MIG, IP-10 and ITAC), or the
ability of a polypeptide fragment, variant or derivative of the invention to
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multimerize is being evaluated, binding can be assayed, e.g., by means well-
known in the art” (id. at ¶ [0066]).
16. The Specification also states:
[A]ssays described herein (and otherwise known in the art[)]
may routinely be applied to measure the ability of G-protein
Chemokine Receptor polypeptides and fragments, variants
derivatives and analogs thereof to elicit G-protein Chemokine
Receptor related biological activity. For example, techniques
described herein and otherwise known in the art may be applied
or routinely modified to assay for the ability of the
compositions of the invention to inhibit or stimulate Thl cell
migration (e.g., MIG- ITAC- or IP-10-mediated Thl cell
migration).
(Id. at ¶ [0067].)
17. In addition, the Specification states that “[i]t is believed that the
extracellular domains of G-protein Chemokine Receptor are important for
interactions between G-protein Chemokine Receptor and its ligands (e.g.,
MIG, ITAC, IP-10)” (id. at ¶ [0072]).
18. The Specification also states that “a cellular compartment, such
as a membrane or a preparation thereof, may be prepared from a cell that
expresses a molecule that binds G-protein Chemokine Receptor ligand (e.g.,
ITAC, MIG, or IP-10)” (id. at ¶ [0531]).
19. In addition, the Specification states:
[A]ntagonists according to the present invention include soluble
forms of G-protein Chemokine Receptor (e.g., fragments of
G-protein Chemokine Receptor shown in Figure 1 (SEQ ID
NO:2) . . . that include the ligand binding domain and/or
extracellular domain of G-protein Chemokine Receptor). Such
soluble forms of the G-protein Chemokine Receptor, which
may be naturally occurring or synthetic, antagonize G-protein
Chemokine Receptor mediated signaling by competing with
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native G-protein Chemokine Receptor for binding to G-protein
Chemokine Receptor ligand (e.g., MIG, ITAC, IP-10), and/or
by forming a multimer that may or may not be capable of
binding the receptor, but which is incapable of inducing signal
transduction. Preferably, these antagonists inhibit G-protein
Chemokine Receptor mediated stimulation of lymphocyte (e.g.,
T-cell) proliferation, differentiation, and/or activation.
(Id. at ¶ [0553].)
20. The Specification also states that “polypeptides . . . of the
present invention are used as a[n] inhibitor of . . . T cell migration in
endothelial cells. This activity disrupts tissue architecture or cognate
responses and is useful, for example in disrupting immune responses, and
blocking sepsis.” (Id. at ¶ [0630].)
21. Lasagni, a post-filing reference published on June 2, 2003,
discloses that the “chemokines CXCL9/Mig, CXCL10/IP-10, and
CXCL11/I-TAC regulate lymphocyte chemotaxis, mediate vascular pericyte
proliferation, and act as angiostatic agents, thus inhibiting tumor growth”
and that these “activities are apparently mediated by a unique G protein-
coupled receptor, termed CXCR3 . . . (renamed CXCR3-A)” (Lasagni 1537
(Abstract)). Appellant states, and the Examiner does not dispute, that the
protein of SEQ ID NO: 4 is the protein now known as CXCR3-A (App.
Br. 8).
22. Lasagni also discloses a distinct “receptor named CXCR3-B,
derived from an alternative splicing of the CXCR3 gene that mediates the
angiostatic activity of CXCR3 ligands” (Lasagni 1537 (Abstract)).
Appellant states, and the Examiner does not dispute, that the protein of SEQ
ID NO: 2 is the protein now known as CXCR3-B (App. Br. 8).
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23. In addition, Lasagni discloses that “the interaction of CXCL9
[Mig], CXCL10 [IP-10], and CXCL11 [I-TAC] with CXCR3 . . . results in
the chemotaxis of activated Th1 cells” (Lasagni 1538).
24. Lasagni also discloses that CXCR3-B binds to Mig, IP-10, and
I-TAC (id. at 1539).
PRINCIPLES OF LAW
Section 101 requires a utility that is both substantial and specific. A
substantial utility requires:
show[ing] that an invention is useful to the public as disclosed
in its current form, not that it may prove useful at some future
date after further research. Simply put, to satisfy the
“substantial” utility requirement, an asserted use must show that
that claimed invention has a significant and presently available
benefit to the public.
In re Fisher, 421 F.3d 1365, 1371 (Fed. Cir. 2005). A specific utility is “a
use which is not so vague as to be meaningless.” Id. In other words, “in
addition to providing a ‘substantial’ utility, an asserted use must also show
that [the] claimed invention can be used to provide a well-defined and
particular benefit to the public.” Id.
[T]he PTO has the initial burden of challenging a presumptively
correct assertion of utility in the disclosure. Only after the PTO
provides evidence showing that one of ordinary skill in the art
would reasonably doubt the asserted utility does the burden
shift to the applicant to provide rebuttal evidence sufficient to
convince such a person of the invention’s asserted utility.
In re Brana, 51 F.3d 1560, 1566 (Fed. Cir. 1995) (citation omitted).
“Enablement, or utility, is determined as of the application filing
date.” Id. at 1567 n.19. However, post-filing evidence “can be used to
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substantiate any doubts as to the asserted utility [when it] pertains to the
accuracy of a statement already in the specification.” Id.
In addition, “[i]t is well established that the enablement requirement
of § 112 incorporates the utility requirement of § 101.” In re Fisher, 421
F.3d at 1378.
ANALYSIS
The Specification discloses that “polypeptides . . . of the present
invention are used as a[n] inhibitor of . . . T cell migration in endothelial
cells. This activity disrupts tissue architecture or cognate responses and is
useful, for example in disrupting immune responses, and blocking sepsis.”
(Finding of Fact (FF) 20.) Appellant argues that “inhibitors of receptor-
ligand interaction would be useful for inhibiting T-cell migration. . . .
Blocking T-cell migration disrupts the immune response, and can be used in
blocking sepsis.” (App. Br. 7.)
In particular, Appellant argues:
The specification . . . describes HSATU68 as binding to MIG,
IP-10 and I-TAC chemokines (see e.g. paragraphs [0030],
[0063], [0066], [0067], [0072], [0283], [0531], and [0553]). At
the time of filing the specification, these chemokines were all
known as interferon induced T-cell chemoattractants. . . . Thus,
one of ordinary skill would recognize that the identification of
the receptor for these chemokines enables a person of ordinary
skill in the art to obtain antibodies, peptide fragments, or small
molecule inhibitors to block any process mediated by MIG,
IP-10 or I-TAC chemokines.
(App. Br. 6.)
In addition, Appellant argues:
[T]he specification clearly asserts that SEQ ID NO: 2 is a
G-protein chemokine receptor polypeptide which functions as a
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receptor for three different ligands: MIG, IP-10, and ITAC.
The specification continues, describing that these ligands
mediate chemotaxis and Thl cell migration. (See e.g.,
specification at paragraphs [0063], [0066] and [0067]). It is
well known to those skilled in the art that Th-1 cells are critical
participants in the cell-mediated immune response and
inflammation. Accordingly, Appellant has provided at least
one specific and substantial utility for the polypeptide of SEQ
ID NO: 2. Namely, the polypeptide of SEQ ID NO: 2 can be
used to mediate the immune response by influencing the
migration of Thl cells via MIG, IP-10 and ITAC binding.
(Reply Br. 3.)
We agree with Appellant that the Specification “asserts that SEQ ID
NO: 2 is a G-protein chemokine receptor polypeptide which functions as a
receptor for three different ligands: MIG, IP-10, and ITAC” (App. Br. 6;
FF 10-11 & 13-19). The Specification also asserts that MIG, IP-10 and
ITAC mediate chemotaxis and Th1 cell migration (FF 14 & 16). In support
of the assertion that SEQ ID NO: 2 is a G-protein chemokine receptor, the
Specification states that SEQ ID NO: 2 “exhibit[s] homology at the amino
acid level to a human interleukin-8 receptor beta[, a known chemokine
receptor,] . . . as shown in Figure 3” (FF 12 & 7). The Specification also
states that the polynucleotide that encodes the claimed protein was
“discovered in a human genomic library derived from human activated
T cells” (FF 12). In addition, Murphy, which was published before the filing
date of the current application, states that I-TAC, Mig, and IP-10 each
“chemoattract and induce calcium flux in activated T cells,” indicating that
this was known in the art at the time the current application was filed (FF 9,
4, & 1).
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Furthermore, it is undisputed that Lasagni confirms the Specification
assertions that SEQ ID NO: 2 is a G-protein chemokine receptor for MIG,
IP-10, and ITAC (FF 22 & 24). Lasagni also confirms that the interaction of
Mig, IP-10, and I-TAC with CXCR3 “results in the chemotaxis of activated
Th1 cells” (FF 23). Although Lasagni was published after filing of the
present application (FF 1 & 21), we agree with Appellant that it “can be used
to substantiate any doubts as to the asserted utility since [it] pertains to the
accuracy of a statement already in the specification.” In re Brana, 51 F.3d at
1567 n.19.
In view of the identification of the claimed protein as a chemokine
receptor, the identification of three ligands for this receptor, and the
disclosure that these chemokine ligands mediate Th1 cell migration, we
agree with Appellant that the Examiner has not adequately explained why
one of ordinary skill in the art would not believe that the polypeptide of SEQ
ID NO: 2 could be used “to mediate the immune response by influencing the
migration of Thl cells via MIG, IP-10 and ITAC binding” (Reply Br. 3) or
why this would not be considered a substantial and specific utility.
The Examiner argues that the biological function of the claimed
protein is not known or disclosed. However, the utility is based on the
protein’s ability to bind to known chemokines and therefore inhibit the
chemokine biological function. Thus, we are not persuaded by the
Examiner’s arguments.
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CONCLUSION
The evidence does not support the Examiner’s conclusion that the
protein of claim 25 lacks utility. We therefore reverse the utility and
enablement rejections of claims 25-34.

REVERSED

alw

MICHELE M. SIMKIN
FOLEY & LARDNER LLP
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