Ex Parte Champion et al

Patent Trial and Appeal Board

Nov 17, 2012

11188417 (P.T.A.B. Nov. 17, 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.
11/188,417 07/25/2005 Brian Robert Champion 674525-2022 8591
20999 7590 11/19/2012
FROMMER LAWRENCE & HAUG
745 FIFTH AVENUE- 10TH FL.
NEW YORK, NY 10151
EXAMINER
BUNNER, BRIDGET E
ART UNIT PAPER NUMBER
1647
MAIL DATE DELIVERY MODE
11/19/2012 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 PATENT TRIAL AND APPEAL BOARD
__________

Ex parte BRIAN ROBERT CHAMPION,
SILVIA RAGNO, and
LESLEY LYNN YOUNG
__________

Appeal 2011-013014
Application 11/188,417
Technology Center 1600
__________

Before DONALD E. ADAMS, LORA M. GREEN, and
JEFFREY N. FREDMAN, Administrative Patent Judges.

FREDMAN, Administrative Patent Judge.

DECISION ON APPEAL
This appeal under 35 U.S.C. § 134 involves claims to a composition
comprising a modulator of the Notch signaling pathway and an autoantigen.
The Examiner rejected the claims as obvious. We have jurisdiction under 35
U.S.C. § 6(b). We affirm.
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Statement of the Case
Background
The Specification teaches “that Notch signalling provides a „bystander
effect‟ or „bystander suppression effect‟ which may be used in a wide
variety of ways to suppress unwanted immune responses in immune diseases
and disorders” (Spec. 4, ll. 2-4). According to the Specification “this „Notch
bystander effect‟ may, for example, be used to provide targeted immune
suppression at a disease locus with less of an undesirable general
immunosuppressant effect on the whole body” (Spec. 4, ll. 4-6).
The Claims
Claims 1, 2, and 23 are on appeal.
1
Claim 1 is representative and
reads as follows:
1. A composition comprising
i) a modulator of the Notch signalling pathway,
wherein the modulator of the Notch signalling pathway
comprises or encodes
(a) a Notch ligand Delta-Serrate Lag2 (DSL)
domain, wherein the DSL domain has at least 95%
identity to DSL domain of human Jagged 1, human
Jagged 2, human Delta 1, human Delta 3, or human
Delta 4, and
(b) at least 2 to 8 Epidermal Growth Factor
(EGF)-like domains, wherein the EGF-like domains
have at least 95% identity to EGF-like domains of
human Jagged 1, human Jagged 2, human Delta 1,
human Delta 3, or human Delta 4;
ii) an autoantigen or bystander antigen or antigenic
determinant thereof, or a polynucleotide encoding an
autoantigen or bystander antigen or antigenic determinant
thereof; and optionally,
iii) a pharmaceutically acceptable carrier.

1
Claims 4, 6, 7, 17-22, and 24-29 were withdrawn (see App. Br. 3).
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The Issues
A. The Examiner rejected claims 1, 2, and 23 under 35 U.S.C. § 103(a)
as obvious over Lamb1
2
and Lamb2
3
(Ans. 5-7).
B. The Examiner rejected claims 1 and 23 on the ground of nonstatutory
obviousness-type double patenting as being unpatentable over claims 1 and
19 of copending US application Serial No. 11/231,494 (Final Rej. 2-3).
A. 35 U.S.C. § 103(a) as obvious over Lamb1 and Lamb2
The Examiner finds that
Lamb1 teach a molecule comprising a Notch-ligand moiety
operably linked to a T cell allergen or antigen moiety such
that upon exposure to T cells both moieties are capable of
binding to their respective sites . . . Lamb1 disclose that such
a molecule is capable of rendering an antigen/allergen
specific T cell tolerant to the allergen or antigen upon which
the allergen or antigen moiety is based . . . Lambl teach that
with the use of the appropriate allergen or antigen, a Notch-
ligand may be used in accordance with the present invention
to treat a disease or infection . . . Lambl teach that Notch
ligands have a diagnostic DSL domain comprising 20-22
amino acids at the amino terminus of the protein and
between 3-8 EGF-like repeats on the extracellular surface .
. . Lambl teach that Notch ligands have been described in
many vertebrate and invertebrate species, and include Delta
(specifically Delta l), Serrate, and Jagged

(Ans. 5-6). The Examiner finds that “Lamb2 teach incubating a lymphocyte
or APC cell obtained from a human or animal patient with (i) a composition
capable of upregulating expression of an endogenous Notch or Notch ligand

2
Lamb et al., WO 98/20142 A1, published May 14, 1998, hereafter referred
to as “Lamb1”, consistent with the usage of the Examiner and Appellants.
3
Lamb et al., WO 00/36089 A2, published June 22, 2000, hereafter referred
to as “Lamb2”.
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and (ii) an allergen or antigen” (Ans. 6). The Examiner finds that “Lamb2
disclose that APCs and/or lymphocytes may be used to treat an ongoing
immune response (such as an allergic condition or an autoimmune disease)
or may be used to generate tolerance” (Ans. 6). The Examiner finds that
“Lamb2 also disclose that it is preferred to use antigens known to be
associated with autoimmune diseases, such as insulin (diabetes)” (Ans. 6).
The Examiner finds it obvious “to modify the Notch ligand-antigen
composition as taught by Lamb1 by utilizing the diabetes antigen (insulin) as
taught by Lamb2” (Ans. 7). The Examiner finds that the “person of ordinary
skill in the art would have been motivated to make that modification because
diabetes is an autoimmune disease state modulated by T cells where there is
a failure of the proper regulation of tolerance” (Ans. 7).
The issue with respect to this rejection is: Does the evidence of record
support the Examiner‟s conclusion that Lamb1 and Lamb2 render Claim 1
obvious?
Findings of Fact
1. Lamb1 teaches the “use of therapeutic compounds in the
modification of T-cell activation. In particular it relates to their use in
modulating the interaction between Notch protein family members and their
ligands and to the use of such compounds in the therapy of conditions such
as graft rejection, autoimmunity” (Lamb1 1, ll. 3-7).
2. Lamb1 teaches
a molecule comprising a Notch-ligand moiety operably
linked to a T cell allergen or antigen moiety such that upon-
exposure to T cells both-moieties are capable of binding to
their respective sites. Such a molecule is capable of
rendering an antigen/allergen specific T cell tolerant to the
allergen or antigen upon which the allergen or antigen
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moiety is based, as the specificity required of the Notch-
ligand moiety is provided by the close proximity of the
allergen or antigen moiety

(Lamb1 7, l. 20 to 8, l. 2).
3. Lamb1 teaches that “it has been observed that by exposing a
population of naive T cells to a Notch-ligand expressed by an APC in the
presence of an allergen or antigen, the Notch-ligand is capable of making the
T cell population tolerant to said allergen or antigen” (Lamb1 4, ll. 9-12).
4. Lamb1 teaches that “[d]iseased or infectious states that may be
described as being mediated by T cells include any one or more of asthma,
allergy, graft rejection, autoimmunity” (Lamb1 8, ll. 17-19).
5. Lamb1 teaches that the “Notch ligands have a diagnostic DSL
domain (D.Delta, S, Serrate, L,Lag2) comprising 20-22 amino acids at the
amino terminus of the protein and between 3-8 EGF-like repeats on the
extracellular surface. The proteins have a short cytoplasmic tail with no
conserved functional domains” (Lamb1 2, ll. 12-15).
6. Lamb1 teaches that:
Notch, Delta and Serrate were first described in Drosophila
and therefore represent prototypic proteins of the Notch
receptor and Notch-ligand family members respectively.
Multiple Notch proteins and ligands have now been
described in many invertebrate and vertebrate species but
their nomenclature may differ from that used in the fly. For
example Notch is a homolog of Lin 12 and Glp 1,
Serrate/Delta are homologs of Jagged, Apx1 and Lag-2.

(Lamb1 11, ll. 14-19).
7. Lamb1 teaches that “[p]harmaceutical formulations of the
present invention may be formulated according to principles well known in
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the art. Thus the nature of the excipient and the amount of activity will
depend upon the compound of the present invention which is to be
formulated” (Lamb 11, ll. 21-24).
8. Lamb2 teaches the “use of compositions capable of
upregulating expression of an endogenous Notch or Notch ligand in such
methods. These compositions, antigen presenting cells and lymphocytes may
be used in immunotherapy” (Lamb2 1, ll. 7-10).
9. Lamb2 teaches
a method for producing a lymphocyte or antigen presenting
cell (APC) having tolerance to an allergen or antigen which
method comprises incubating a lymphocyte or APC obtained
from a human or animal patient with (i) a composition
capable of upregulating expression of an endogenous Notch
or Notch ligand in the lymphocyte and/or APC and (ii) the
allergen or antigen

(Lamb2 2, ll. 24-27).
10. Lamb2 teaches that:
Particular examples of mammalian Notch ligands identified
to date include the Delta family, for example Delta-l
(Genbank Accession No. AF003522 - Homo sapiens), Delta-
3 (Genbank Accession No. AF084576 - Rattus norvegicus)
and Delta-like 3 (Mus musculus), the Serrate family, for
example Serrate-l and Serrate-2 (WO97/01571,
WO96/27610 and WO92/19734), Jagged-l and Jagged-2
(Genbank Accession No. AF029778 – Homo sapiens), and
LAG-2. Homology between family members is extensive.
For example, human Jagged-2 has 40.6% identity and 58.7%
similarity to Serrate.

(Lamb2 7, ll. 23-29).
11. Lamb2 teaches that “it is preferred to use antigens known to be
associated with auto-immune diseases such as myelin basic protein
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(associated with multiple sclerosis), collagen (associated with rheumatoid
arthritis), and insulin (diabetes), or antigens associated with rejection of non-
self tissue such as MHC antigens” (Lamb 2 15, l. 32 to 16, l. 3).
12. Lamb2 teaches that:
The APCs and/or lymphocytes may thus be used to treat an
ongoing immune response (such as an allergic condition or
an autoimmune disease) or may be used to generate
tolerance in an immunologically lymphocytes cells of the
present invention may be used in therapeutic methods for
both treating and preventing diseases characterised by
inappropriate lymphocyte activity in animals and humans.
The APCs and/or lymphocytes may be used to confer
tolerance to a single antigen or to multiple antigens.

(Lamb2 20, ll. 20-26).
Principles of Law
“In proceedings before the Patent and Trademark Office, the
Examiner bears the burden of establishing a prima facie case of obviousness
based upon the prior art.” In re Fritch, 972 F.2d 1260, 1265 (Fed. Cir.
1992).
“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.
Moreover, an “[e]xpress suggestion to substitute one equivalent for
another need not be present to render such substitution obvious.” In re Fout,
675 F.2d 297, 301 (CCPA 1982). As noted by the Court in KSR, “[a] person
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of ordinary skill is also a person of ordinary creativity, not an automaton.”
550 U.S. at 421.
Analysis
Lamb1 teaches that “it has been observed that by exposing a
population of naive T cells to a Notch-ligand expressed by an APC in the
presence of an allergen or antigen, the Notch-ligand is capable of making the
T cell population tolerant to said allergen or antigen” (Lamb1 4, ll. 9-12; FF
3). Lamb1 teaches that exemplary modulators of the Notch signaling
pathway where the “Notch ligands have a diagnostic DSL domain (D.Delta,
S, Serrate, L,Lag2) comprising 20-22 amino acids at the amino terminus of
the protein and between 3-8 EGF-like repeats on the extracellular surface.
The proteins have a short cytoplasmic tail with no conserved functional
domains” (Lamb1 2, ll. 12-15; FF 5). Lamb1 teaches the use of
pharmaceutical carriers (FF 7).
Lamb2 teaches human sequences for the Notch ligand as well as the
EGF domains (FF 10). Lamb2 teaches antigens including autoantigens (FF
11).
Applying the KSR standard of obviousness to the findings of fact, we
conclude that the person of ordinary creativity would have predictably
substituted the human Notch ligands for the Drosophila Notch ligands for
treatment of humans (FF 10) and would have predictably used autoantigens
in order to treat diseases such as Type 1 diabetes (FF 11-12) since Lamb2
teaches the use of endogenous human antigens and ligands for the treatment
methods (FF 9). Such a combination is merely a “predictable use of prior art
elements according to their established functions.” KSR, 550 U.S. at 417.
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Appellants contend that “[o]ne of ordinary skill in the art would not
combine Lamb 1 and Lamb2 with an expectation of successfully arriving at
the claimed invention” (App. Br. 9). Appellants contend that “Lamb2 shows
the use of an autoantigen with a composition that is capable of upregulating
expression of endogenous Notch or Notch ligands. Therefore, Lamb2
teaches away from the use of the Notch ligand in Lambl. Even if Lamb 1
and Lamb2 have the same purpose, they teach contrasting means of
achieving it” (App. Br. 9).
We are not persuaded. Lamb1 teaches the use of a notch ligand,
antigen, and pharmaceutical carrier to induce tolerance in T-cells (FF 4).
The Examiner solely relies on Lamb2 to teach that human notch ligands
were known (FF 10) and that autoantigens were also reasonable targets for
induction of tolerance (FF 12). The teaching of two different alternative
approaches by Lamb1 and Lamb2 reasonably suggests that multiple
approaches will effectively function in the induction of tolerance. Kubin
stated that “[r]esponding to concerns about uncertainty in the prior art
influencing the purported success of the claimed combination, this court [in
O’Farrell] stated: „[o]bviousness does not require absolute predictability of
success … all that is required is a reasonable expectation of success.”‟ In re
Kubin, 561 F.3d 1351, 1360 (Fed. Cir. 2009) (citing In re O'Farrell, 853
F.2d 894, 903-904 (Fed. Cir. 1988)). We conclude that given the direct
suggestion in the prior art of Lamb1 that tolerance can be induced by notch
ligands, antigens and pharmaceutical excipients (FF 1-7) along with the
teaching in Lamb2 of particular notch ligands and antigens for tolerance
induction (FF 8-12) reasonably supports the Examiner‟s finding of a
reasonable expectation of success.
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We also do not find the teaching away argument persuasive. A
teaching away requires a reference to actually criticize, discredit, or
otherwise discourage the claimed solution. See In re Fulton, 391 F.3d 1195,
1201 (Fed. Cir. 2004) (“The prior art‟s mere disclosure of more than one
alternative does not constitute a teaching away from any of these alternatives
because such disclosure does not criticize, discredit, or otherwise discourage
the solution claimed”). Appellants do not identify, and we do not find, any
teaching in the cited Lamb1 and Lamb2 references which criticizes,
discredits, or otherwise discourages the claimed combination.
Appellants contend that “there are discrepancies for how autoantigens
are used in Lamb2 and how they are to be applied in Lamb 1; if these cited
references were combined, the skilled artisan would not apply the
autoantigen of Lamb2 to Lamb 1 with the expectation of success or with
predictable results” (App. Br. 9).
We are not persuaded. In KSR, the Supreme Court found that
The principles underlying [earlier] cases are instructive
when the question is whether a patent claiming the
combination of elements of prior art is obvious. 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 at 417. The Examiner reasonably relies upon this predictable variation
rationale for supporting the prima facie case. Particularly, the Examiner
finds it reasonable to use the antigens disclosed in Lamb2 in the method of
Lamb1. Appellants provide no evidence why this substitution would not
have been expected to succeed given the broad reference to antigens given
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by Lamb1 (see, e.g., FF 2). Lamb2 similarly provides a large variety of
antigens which are indicated as available (see FF 11). Consequently, the
evidence of the references is that any antigen would be expected to function
in the method of Lamb1 or in the method of Lamb2 and Appellants provide
no rebuttal evidence.
Conclusion of Law
The evidence of record supports the Examiner‟s conclusion that
Lamb1 and Lamb 2 render claim 1 obvious.
B. Double Patenting
We summarily affirm the provisional obviousness-type double
patenting rejection. See Manual of Patent Examining Procedure § 1205.02
(“If a ground of rejection stated by the examiner is not addressed in the
appellant‟s brief, that ground of rejection will be summarily sustained by the
Board.”); See also In re Berger, 279 F.3d 975, 984 (Fed. Cir. 2002) (in
which the Board affirmed an uncontested rejection of claims under 35
U.S.C. 112, second paragraph, and on appeal the Federal Circuit affirmed
the Board‟s decision and found that the appellant had waived his right to
contest the indefiniteness rejection by not presenting arguments as to error in
the rejection on appeal to the Board).
SUMMARY
In summary, we affirm the rejection of claim 1 under 35 U.S.C.
§ 103(a) as obvious over Lamb1 and Lamb2. Pursuant to 37 C.F.R.
§ 41.37(c)(1), we also affirm the rejection of claims 2 and 23 as these claims
were not argued separately.

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We affirm the rejection of claims 1 and 23 on the ground of
nonstatutory obviousness-type double patenting as being unpatentable over
claims 1 and 19 of copending US application Serial No. 11/231,494.
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
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