Ex Parte Figdor et al

Board of Patent Appeals and Interferences

Jul 27, 2011

10625202 (B.P.A.I. Jul. 27, 2011)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte CARL GUSTAV FIGDOR,
TEUNIS BERNARD HERMAN GEIJTENBEEK,
YVETTE VAN KOOYK, and RUURD TORENSMA
__________

Appeal 2011-003031
Application 10/625,202
Technology Center 1600
__________

Before ERIC GRIMES, LORA M. GREEN, 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 method
for reducing a T-cell mediated immune response. The Examiner rejected the
claims as non-enabled. We have jurisdiction under 35 U.S.C. § 6(b). We
reverse.

Appeal 2011-003031
Application 10/625,202

2
Statement of the Case
Background
The Specification teaches modulating “the adhesion of C-type lectin
receptors on the surface of dendritic cells to the ICAM-receptors on the
surface of T cells. By modulating this adhesion, both dendritic cell-T cell
interactions, such as cluster formation and antigen presentation, as well as
for instance primary T cell responses depend[e]nt thereon, can be
influenced” (Spec. 1, ll. 10-14).
The Claims
Claims 1, 3, 4, 6, 7, 19, and 23-27 are on appeal. Claim 1 is
representative and reads as follows:
1. A method for reducing a T-cell mediated immune
response in an animal by inhibiting an interaction
between a dendritic cell and a T cell, comprising
administering to an animal in need of reducing said
immune response an antibody which binds to a protein
with the amino acid sequence of SEQ ID NO: 2 (DC-
SIGN) on the surface of a dendritic cell, wherein said
antibody reduces one or more interactions between a
dendritic cell and a T cell thereby reducing said immune
response in the animal, and wherein the animal is not
infected with HIV.

The issue
The Examiner rejected claims 1, 3, 4, 6, 7, 19, and 23-27 under 35
U.S.C. § 112, first paragraph, as failing to comply with the enablement
requirement (Ans. 3-4).
The Examiner finds that the “invention is drawn to reducing T-cell
mediated immune responses by administering an antibody that binds SEQ
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ID #2” (Ans. 4). The Examiner finds that the “post filing art, Geijtenbeek
Cell Vol. 100 page 575-585, from IDS 7/31/06, shows that not all antibodies
that bind the sequence have the same function” (id.). The Examiner finds
that the “Specification provides no guidance or direction or teaching on
specific regions the antibody binds to, or what the variants of the sequence
are that can function and give rise to antibodies that have the same function”
(id.).
Appellants contend that the
instant application provides several examples, including in
vitro data derived from cell based assays, to support the
claimed subject matter. For example, Example 2
demonstrates that an antibody against DC-SIGN can inhibit
the interaction between DC-SIGN (on the surface of
dendritic cells) and an ICAM receptor (on the surface of T
cells.

(App. Br. 4). Appellants contend that they “have submitted additional
evidence demonstrating that one of skill in the art would expect that the in
vitro evidence provided in the specification is representative of what occurs
in vivo” (id. at 5). Appellants contend that the “Examiner has not provided
any evidence to suggest that the instantly claimed methods would not be
operative with respect to reducing T-cell mediated immune response in vivo,
thereby failing to meet the burden of establishing a prima facie case of lack
of enablement” (id. at 6).
The issue with respect to this rejection is: Does the evidence of record
support the Examiner‟s conclusion that undue experimentation would have
been required to enable the method of claim 1?

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Findings of Fact
Breadth of Claims
1. Claim 1 is drawn to reducing a T-cell mediated immune
response in an animal, so the claim is broadly drawn to in vivo use (see
Claim 1).
Presence of Working Examples
2. The Specification teaches that to
investigate DC-SIGN in more detail, antibodies against the
ICAM-3 binding receptor were raised. . . . Two hybridomas
were selected, cloned and the resulting antibodies were
named AZN-Dl and AZN-D2. Both purified antibodies
strongly inhibit adhesion of DC to ICAM-3, but do not
affect LFA-I mediated adhesion of monocytes to ICAM-3.

(Spec. 20, ll. 24-31).
3. The Specification teaches that “[f]lowcytometric analysis of an
extensive panel of hematopoietic cells with the AZN-D1/D2 antibodies
demonstrates that the antigen is preferentially expressed by DC” (Spec. 25,
ll. 17-19).
4. The Specification teaches that the “DC-T cell interaction can be
inhibited (approximately 50%) by anti-DC-SIGN antibodies suggesting that
the DC-T cell clustering is also mediated by other surface receptors. Thus,
the DC-T cell clustering is indeed transient and partly mediated by DC-
SIGN/ICAM-3 interactions” (Spec. 27, ll. 26-29).
Amount of Direction or Guidance Presented
5. The Specification teaches that a
compound or composition is in particular administered in
such an amount that the interaction(s) between dendritic
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cells and T cells are altered or modified, more in particular
in such an amount that the adhesion of dendritic cells to T
cells is reduced. This method can be used for preventing
and/or treating disorders of the immune system, as well as to
prevent transplant rejection.

(Spec. 14, ll. 17-22).
State of the Prior Art and Unpredictability of the Art
6. The Examiner finds that Geijtenbeek
1
“shows that not all
antibodies that bind the sequence have the same function” (Ans. 4).
7. Ingulli
2
teaches that although “in vitro experiments strongly
indicate that DC are the initiating APC for T cell responses in vivo,
suggestive evidence supporting this idea has only recently been reported”
(Ingulli 2133, col. 1).
8. Steinman
3
teaches that
In vivo, DCs are found in peripheral tissues, such as the skin
and airways but they can migrate to lymphoid tissues. There,
in the T cell areas, the DCs are in full view of the
circulating, naive lymphocyte repertoire and can even make
chemokines that attract these T cells . . . . The match of the
DC and T cell can then be made via DC-SIGN, allowing the
intimate cross-talk between the two cells to begin . . .
(Steinman 492, col. 2).

1
Geijtenbeek et al., Identification of DC-SIGN, a Novel Dendritic
Cell-Specific ICAM-3 Receptor that Supports Primary Immune
Responses, 100 CELL 575-585 (2000).
2
Ingulli et al, In Vivo Detection of Dendritic Cell Antigen
Presentation to CD4
+
T Cells, 185 J. EXP. MEDICINE 2133-2141
(1997).
3
Steinman, Ralph, DC-SIGN: A Guide to Some Mysteries of
Dendritic Cells, 100 CELL 491-494 (2000).
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9. Pereira
4
teaches that “this study provides proof-of-principle that
an anti-DC-SIGN monoclonal antibody administered in vivo is capable of
targeting APCs in LNs and in the liver” (Pereira 713, col. 1-2).
Principles of Law
When rejecting a claim under the enablement
requirement of section 112, the PTO bears an initial burden
of setting forth a reasonable explanation as to why it
believes that the scope of protection provided by that claim
is not adequately enabled by the description of the invention
provided in the specification of the application.

In re Wright, 999 F.2d 1557, 1561-62 (Fed. Cir. 1993). “[T]he question of
undue experimentation is a matter of degree. The fact that some
experimentation is necessary does not preclude enablement; what is required
is that the amount of experimentation „must not be unduly extensive.”‟ PPG
Indus., Inc. v. Guardian Indus. Corp., 75 F.3d 1558, 1564 (Fed. Cir. 1996).
Factors to be considered in determining whether a
disclosure would require undue experimentation … include
(1) the quantity of experimentation necessary, (2) the
amount of direction or guidance presented, (3) the presence
or absence of working examples, (4) the nature of the
invention, (5) the state of the prior art, (6) the relative skill
of those in the art, (7) the predictability or unpredictability
of the art, and (8) the breadth of the claims.

In re Wands, 858 F.2d 731, 737 (Fed. Cir. 1988).

4
Pereira et al., In Vivo Targeting of DC-SIGN-positive Antigen-
presenting Cells in a Nonhuman Primate Model, 30 J.
IMMUNOTHER. 705-714 (2007).
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Analysis
While the claims are undoubtedly broader (FF 1) than the examples
disclosed in the Specification (FF 2-4), in order to affirm an enablement
rejection we need evidence or scientific reasoning which demonstrates a
requirement for undue experimentation.
The Examiner has not provided any such evidence. The Examiner
cites Geijtenbeek to show that “not all antibodies that bind the sequence
have the same function” (Ans. 4).
We are not persuaded, since it is routine to screen antibodies for a
desired function, and in particular, it is routine to screen antibodies for their
ability to interact with a particular target and inhibit binding of other
molecules to that target. Example 2 of the instant Specification discloses
such a screening (FF 2).
The Examiner provides no evidence or scientific reasoning to support
the conclusion that application of the in vitro assay disclosed in the
examples to in vivo use would require undue experimentation.
We also do not find that the art cited by Appellants suggests undue
experimentation. Ingulli teaches that although “in vitro experiments
strongly indicate that DC are the initiating APC for T cell responses in vivo,
suggestive evidence supporting this idea has only recently been reported”
(Ingulli 2133, col. 1; FF 7). This supports the logic of the invention, which
is that antibodies which impede the ability of dendritic cells to initiate
antigen presentation will reduce immune response. Similarly, Steinman
teaches that DC-SIGN is required to allow “the intimate cross-talk between
the two cells to begin” (Steinman 492, col. 2; FF 8). Finally, Pereira teaches
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that “this study provides proof-of-principle that an anti-DC-SIGN
monoclonal antibody administered in vivo is capable of targeting APCs in
LNs and in the liver” (Pereira 713, col. 1-2; FF 9). This postfiling date art
demonstrates the ability to administer the murine antibody in vivo and its
ability to at least function in binding. (However, see In re Gunn, 537 F.2d
1123 (CCPA 1976) for relevance of postfiling date art).
Conclusion of Law
The evidence of record does not support the Examiner‟s
conclusion that undue experimentation would have been required
to enable the method of claim 1.
SUMMARY
In summary, we reverse the rejection of claims 1, 3, 4, 6, 7, 19, and
23-27 under 35 U.S.C. § 112, first paragraph, as failing to comply with the
enablement requirement.

REVERSED

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