Ex Parte Hawiger et al

Patent Trial and Appeal Board

Sep 27, 2012

09925284 (P.T.A.B. Sep. 27, 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.
09/925,284 08/09/2001 Daniel Hawiger RUJ-001CNCPRCE2 2660
959 7590 09/28/2012
NELSON MULLINS RILEY & SCARBOROUGH LLP
FLOOR 30, SUITE 3000
ONE POST OFFICE SQUARE
BOSTON, MA 02109
EXAMINER
SCHWADRON, RONALD B
ART UNIT PAPER NUMBER
1644
MAIL DATE DELIVERY MODE
09/28/2012 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 DANIEL HAWIGER, MICHEL C. NUSSENZWEIG,
and RALPH M. STEINMAN
__________

Appeal 2012-007915
Application 09/925,284
Technology Center 1600
__________

Before DEMETRA J. MILLS, ERIC GRIMES, and ERICA A. FRANKLIN,
Administrative Patent Judges.

FRANKLIN, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims to
methods for enhancing the development of tolerance to a preselected
antigen. The Patent Examiner rejected the claims as failing to comply with
the written description requirement and as lacking enablement. We have
jurisdiction under 35 U.S.C. § 6(b). We affirm.

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STATEMENT OF THE CASE
Claims 6-9 and 13-21 are on appeal. Independent claims 6, 13, 14,
and 18 are representative and read as follows:
6. A method for enhancing the development of tolerance to a preselected
antigen for which tolerance is desired, in a mammal comprising exposing
ex vivo or in vivo dendritic cells from said mammal to a conjugate
comprising said preselected antigen covalently bound to an anti-human
DEC-205 antibody or an anti-murine DEC-205 antibody that binds to human
DEC-205 under conditions that promote dendritic cell quiescence, said
human DEC-205 protein comprising an amino acid sequence as set forth in
SEQ ID NO: 7, and wherein said preselected antigen is selected from the
group consisting of allergens, autoantigens and antigens participating in
allograft rejection.

13. A method for enhancing the development of tolerance to a preselected
antigen for which tolerance is desired in a mammal, comprising exposing
ex vivo or in vivo dendritic cells from said mammal to a conjugate
comprising said preselected antigen covalently bound to an anti-human
DEC-205 antibody, wherein the antibody is reactive with an amino acid
sequence as set forth in SEQ ID NO: 7, under conditions that promote
dendritic cell quiescence, wherein said preselected antigen is selected from
the group consisting of allergens, autoantigens and antigens participating in
allograft rejection.

14. A method for enhancing the development of tolerance to a preselected
antigen for which tolerance is desired, in a mammal comprising exposing
ex vivo or in vivo dendritic cells from said mammal to a conjugate
comprising said preselected antigen covalently bound to an anti-murine
DEC-205 antibody, wherein the antibody is reactive with an amino acid
sequence as set forth in SEQ ID NO: 7, under conditions that promote
dendritic cell quiescence, and wherein said preselected antigen is selected
from the group consisting of allergens, autoantigens and antigens
participating in allograft rejection.

18. A method for enhancing the development of tolerance to a preselected
antigen in a mammal, the method comprising exposing ex vivo or in vivo
dendritic cells from the mammal to a conjugate comprising the preselected
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antigen bound to an anti-mouse DEC-205 antibody that cross reacts with
human DEC-205 under conditions that promote dendritic cell quiescence,
wherein the mouse DEC-205 protein comprises the amino acid sequence of
SEQ ID NO: 10.

The Examiner rejected the claims as follows:
• claims 6-9 and 13-21 under 35 U.S.C. § 112, first paragraph, as
failing to comply with the written description requirement;
• claims 6-9 under 35 U.S.C. § 112, first paragraph, as failing to
comply with the written description requirement (new matter);
• claims 6-9 and 13-21 under 35 U.S.C. § 112, first paragraph, as
lacking enablement; and
• claims 16 and 17 under 35 U.S.C. § 112, second paragraph as being
indefinite.
1

WRITTEN DESCRIPTION
The Examiner‟s position is that the Specification does not convey to
an artisan that Appellants had possession, at the time of filing, of the
conjugate recited in the claimed method. (Ans. 6.) The Examiner found that
the claim “term [„]human DEC-205[‟] would appear to encompass full
length human DEC-205[,] as well as mutants and variants or alleles of said
human protein….” (Id.) The Examiner found that the while the full length
murine DEC-205 protein was disclosed in the Specification of the parent
application, there was no disclosure of the full length human DEC-205. (Id.)
Specifically, the Examiner found that human DEC-205 contains

1
(Ans. 15.) Appellants do not present the indefiniteness rejection for
review. (App. Br. 5; Ans. 27.) Therefore, we do not address this rejection
further.
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4
approximately 1800 amino acids and that the Specification disclosed
sequences for two peptides derived from the human DEC-205 having 30 and
25 amino acids, respectively, but did not disclose the identity of the
remaining approximately 1750 amino acids. (Id.)
Appellants contend that the Specification‟s “disclosure of the partial
human DEC-205 sequence and the full length murine DEC-205 sequence, in
combination with knowledge available in the art, were sufficient to
demonstrate to one of ordinary skill that they had full possession of the
complete human DEC-205 protein, and antibody conjugates against the
protein, at the time the present application was filed.” (App. Br. 7.)
According to Appellants, the fact that they successfully isolated and
characterized full-length mouse DEC-205 from whole murine thymus using
mAb NLDC-145, an anti-mouse DEC-205 antibody, and successfully raised
antibodies against N-terminal peptides from mouse DEC-205 protein
“provides clear evidence that the partial human DEC-205 sequence
described in the present disclosure put Appellants in possession of the
complete DEC-205 protein and antibodies against the protein.” (Id. at 10.)
Further, Appellants assert that “[i]t was also well within the skill in the art to
have generated full-length human DEC-205 protein, as well as variants of
the human DEC-205 protein.” (Id. at 11.)
Additionally, Appellants submit the Declaration of Dr. Michel
Nussenzweig as evidence that “the cloning techniques and techniques for
generating antibodies described in the specification were ultimately
successfully used to clone and isolate human DEC-205 and to produce
antibodies against full-length human DEC-205.” (Id. at 11.) According to
Appellants, this fact “provides clear evidence that Appellants were in fact
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indeed in possession of the claimed invention based on the descriptive text
provided within the four corners of Appellants‟ originally filed disclosure.”
(Id.)
Moreover, Appellants contend that “the structure and function of
human DEC-205 clearly correlates to that of mouse DEC-205,” such that the
disclosure of an “in-depth characterization of mouse DEC-205, including its
full-length sequence… provides further basis for fully meeting the Written
Description requirement.” (Id. at 8.)
Regarding claims 18-21, Appellants assert that “these claims are
drawn to methods employing antibody conjugates that bind to full length
murine DEC-205 protein … (SEQ ID NO:10),” which sequence is explicitly
disclosed in the Specification. (Id. at 6.) Further, Appellants assert that
while these claims require the antibody conjugates to “cross-react with
human DEC-205, the epitopes of human DEC-205 that the conjugates bind
to are thus, by definition, shared with (i.e., cross-reactive with) murine DEC-
205.” (Id. at 7.) According to Appellants, “the sequence of these epitopes is
provided as part of the full length murine DEC-205 sequence recited in the
claims (SEQ ID NO: 10).” (Id.)
Analysis
I. Claims 6-9 and 13-17
After considering all the evidence and arguments, we conclude that
the disclosure as originally filed did not reasonably convey to those skilled
in the art that the inventors had possession of the subject matter of claims 6-
9 and 13-17 as of the filing date. Ariad Pharm., Inc. v. Eli Lilly and Co.,
598 F.3d 1336, 1351 (Fed Cir. 2010). Appellants do not challenge the
Examiner‟s interpretation of these claims as encompassing methods of using
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antibody conjugates that bind any part of full length human DEC-205, as
well as variants thereof. Nor do Appellants dispute the Examiner‟s finding
that the full length human DEC-205 was not disclosed in the Specification.
Rather, Appellants assert that the inventors, nevertheless, had full possession
of the complete human DEC-205 protein, and antibody conjugates against
the protein, at the time the application was filed, as evidenced by the
disclosure of the partial human DEC-205 sequences, the full length murine
DEC-205 sequence, and the skill and knowledge available in the art to
generate full-length human DEC-205 and its variants. (App. Br. 7.)
According to Appellants, Dr. Nussenzweig‟s declaratory testimony that “the
cloning techniques and techniques for generating antibodies described in the
specification were ultimately successfully used to clone and isolate human
DEC-205 and to produce antibodies against full-length human DEC-205”
also provides evidence that the inventors were in possession of the claimed
invention. (Id. at 11.)
We disagree with Appellants. Dr. Nussenzweig‟s declaration refers to
a cloned human DEC-205 sequence that was not disclosed in the
Specification. Moreover, the fact that Dr. Nussenzweig “ultimately
successfully” cloned and isolated human DEC-205 and produced antibodies
against full length human DEC-205 does not establish that the inventors
were in possession of the subject matter at the time the application was filed.
Consequently, while we recognize Dr. Nussenzweig‟s apparent expertise in
the field of immunology, we do not accord his testimony persuasive weight.
The written description requirement “requires a description of an invention,
not an indication of a result that one might achieve if one made that
invention.” Regents of the University of California v. Eli Lilly & Co., 119
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F.3d 1559, 1568 (Fed. Cir. 1997). Indeed, to comply with the written
description requirement, an applicant must “describe[] the invention, with all
its claimed limitations, not that which makes it obvious….” Id. at 1566
(citation omitted). Thus, Appellants have not satisfied this requirement by
asserting that their disclosure, in combination with the skill and knowledge
available in the art, would have allowed an artisan to generate, i.e.,
eventually gain possession of, the undisclosed full-length human DEC-205
and its variants. Accordingly, we affirm the rejection of claims 6-9 and 13-
17.
II. Claims 18-21
While we agree with Appellants that the full length murine DEC-205
protein is explicitly disclosed in the Specification as SEQ ID NO:10, we do
not agree that this disclosure provides evidence that the inventors were in
possession of the recited antibody conjugates, wherein the antibody cross
reacts with human DEC-205. Specifically, Appellants have not provided
evidence establishing such possession by merely asserting that “the epitopes
of human DEC-205 that the conjugates bind to are …, by definition, shared
with (i.e., cross-reactive with) murine DEC-205.” (App. Br. 7.) Appellants
have not described which epitopes of murine DEC-205 are shared with (i.e.,
cross-reactive with) those of human DEC-205, and therefore have not
adequately shown that they were in possession of antibody conjugates
binding to such epitopes at the time the application was filed.
Accordingly, we affirm the rejection of claims 18-21.

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NEW MATTER
The Examiner rejected claims 6-9 as containing new matter. (Ans. 9.)
We do not reach the new matter rejection, as we have previously affirmed
the Examiner‟s rejection of these claims as failing to comply with the
written description requirement.

ENABLEMENT
The Examiner‟s position is that the Specification is not enabling for
the claimed methods. (Ans. 10.) The Examiner found that the Specification
does not disclose how to use the instant invention for the enhancing of
tolerance or treating allograft rejection in humans in vivo or treating
autoimmune disease in humans in vivo. (Id.) The Examiner found that the
Specification disclosed data resulting from experiments in mice, however,
no diseases were actually treated. (Id. at 14.) The Examiner found the state
of the art is unpredictable in the absence of evidence as to how to use the
invention. (Id. at 10.) In particular, the Examiner found that Nossal
2
taught
that „“[t]here has been a great deal of discussion as to whether suppression
can be achieved in therapeutic models by applying the principles coming
from model situations.”‟ (Id. at 12-13.) The Examiner also found that
Nossal explained that animal models are not necessarily analogous to the
situations encountered in human disease. (Id. at 13.) The Examiner found
that the Specification provided no working examples demonstrating that the
claimed invention can be used for the induction of tolerance/treatment of
disease in vivo in humans or any animal model. (Id.) According to the

2
Gustav J.V. Nossal, Immunologic Tolerance, Fundamental Immunology
(1989).
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Examiner, it is well known in the art that rodent models for the study of
transplantation do not produce results that are readily applicable to humans.
(Id.)(citing Tueveson‟s
3
discussion of the ease with which rejection is
usually suppressed in rodent models as compared to humans). Additionally,
the Examiner found that Mestas
4
disclosed that the immune response of mice
differs in numerous significant ways from the immune response in humans.
(Id. at 15.) According to the Examiner, the state of the art is, thus, that it is
highly unpredictable whether any particular method can be used to
successfully achieve allograft transplantation in humans. (Id. at 13.)
Further, the Examiner found that the Specification does not provide
evidence regarding the use of the claimed method to treat autoimmune
disease, as recited in claims 6 and 13. (Id.) The Examiner found that the
high degree of unpredictability in the art is evidenced by (a) Spack,
5
which
discusses unsuccessful attempts to treat an autoimmune disease (Multiple
Sclerosis) by inducing tolerance to myelin protein and (b) McKown,
6
which
explained that attempts to treat an autoimmune disease (rheumatoid arthritis)
by inducing tolerance to collagen have been unsuccessful. (Id. at 13-14.)

3
G. Tueveson et al., New Immunosuppressants: Testing and Development in
Animal Models and the Clinic: with Special Reference to DSG, 136
Immunology Review 101-107 (1993).
4
Mestas et al., Of Mice and Not Men: Differences between Mouse and
Human Immunology, 172 Journal of Immunology 2731-2738 (2004).
5
Edward G. Spack, Antigen-specific therapies for the treatment of multiple
sclerosis: a clinical trial update, 6(11) Exp. Opin. Invest. Drugs 1715-1727
(1997).
6
McKown et al., Lack of Efficacy of Oral Bovine Type II Collagen Added to
Existing Therapy in Rheumatoid Arthritis, 42(6) Arthritis & Rheumatism
1204-1208 (1999).
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Based on the foregoing, the Examiner concluded that undue
experimentation would be required of a skilled artisan to practice the
claimed invention. (Id. at 15.)
Appellants contend that the Specification is enabling. (App. Br. 14.)
Specifically, Appellants assert that the Specification discloses “in vivo
experiments in mice demonstrating that (1) antigen delivered to dendritic
cells in vivo induces persistent T cell activation …, (2) the absence of
persistent T cell activation in mice injected with an anti-DEC-205 antibody
fused to hen egg lysozyme (αDEC/HEL) is not due to a lack of antigen and,
therefore, that targeting of antigen to DEC-205 causes persistent T cell
activation …, and (3) techniques for assessing dendritic cell function in mice
receiving multiple doses of an anti-DEC-205 antibody fused to hen egg
lysozyme (αDEC/HEL).” (Id.) According to Appellants, based on these in
vivo working examples in mice, which “were (and still are) widely accepted
animal models for assessing the clinical value of biological therapeutics,” a
skilled artisan would not doubt that the disclosed mouse data correlates with
the claimed invention nor that the claimed methods are fully enabled. (Id.)
Regarding McKown, Appellants assert that, contrary to the
Examiner‟s suggestion, the reference does not support a lack of
predictability for the claimed invention. (Id. at 15.) According to
Appellants, McKown provided many rationales for the failure of the
combination therapies to provide significant clinical improvement in the
disease, “none of which implicate a failure to induce tolerance to
collagen per se.” (Id.) Moreover, Appellants assert that McKown‟s studies
“did not involve targeting antigen (e.g., collagen) to DEC-205 and dendritic
cells… [and] [a]s such, the teachings do not speak to the predictability of the
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presently claimed invention.” (Id.) Similarly, Appellants assert that
Spack‟s studies did not establish any unpredictability of the claimed
invention because its studies also did not involve targeting antigen (e.g.,
collagen) to DEC-205 and dendritic cells. (Id.) Regarding Tueveson,
Appellants assert that the reference only suggested that data from small
animal models should not be the sole basis for clinical decision making. (Id.
at 16.) As for Mestas, Appellants assert that the reference teaches that the
differences between mice and humans “should be taken into account when
using mice as preclinical models of human disease.” (Id.)
Analysis
“[T]o be enabling, the specification of a patent must teach those
skilled in the art how to make and use the full scope of the claimed invention
without „undue experimentation.”‟ Genentech, Inc. v. Novo Nordisk, A/S,
108 F.3d 1361, 1365 (Fed. Cir. 1997)(quoting In re Wright, 999 F.2d 1557,
1561 (Fed. Cir. 1993)). “That some experimentation may be required is not
fatal; the issue is whether the amount of experimentation required is
„undue.”‟ In re Vaeck, 947 F.2d 488, 495 (Fed. Cir. 1991). Some
experimentation, even a considerable amount, is not “undue” if, e.g., it is
merely routine, or if the specification provides a reasonable amount of
guidance as to the direction in which the experimentation should proceed.
See In re Wands, 858 F.2d 731, 737 (Fed. Cir. 1988).
Here, after considering all of the evidence and arguments, we agree
with Appellants that based upon the disclosures in the Specification, the skill
in the art, the state of the prior art, and the breadth of the claims, a skilled
artisan would not have had to resort to undue experimentation to use the
claimed methods for enhancing the development of tolerance to a
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preselected antigen in a mammal. We agree with Appellants that the art
recognized the mouse as an acceptable animal model for assessing the
clinical value of biological therapeutics. While the mouse model differs
from a human model, the Examiner has not established that correlating the
data from the mouse model to the human would have required an artisan to
resort to undue experimentation. See In re Wright, 999 F.2d 1557, 1562
(Fed. Cir. 1993)(The Examiner has the initial burden to establish a
reasonable basis to question the enablement provided for the claimed
invention.).
The evidence cited by the Examiner in support of his conclusion of
nonenablement is concerned largely with the difficulty or unpredictability of
achieving clinically useful treatment of disease in humans (see Answer
12-14). The claims, however, are directed to methods of “enhancing the
development of tolerance to a preselected antigen” (e.g., claim 6), and the
Examiner has not established that the only practical utility of the claimed
method is in treatment of human disease. Thus, because the claims do not
require achieving a therapeutically effective result, enabling the claimed
method does not require that result either. See CFMT, Inc. v. Yieldup Int’l
Corp., 349 F.3d 1333, 1338 (Fed. Cir. 2003) (“Title 35 does not require that
a patent disclosure enable one of ordinary skill in the art to make and use a
perfected, commercially viable embodiment absent a claim limitation to that
effect.”).
Accordingly, we reverse the non-enablement rejection.
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SUMMARY
We affirm the rejection of claims 6-9 and 13-21 under 35 U.S.C. §
112, first paragraph, as failing to comply with the written description
requirement;
we reverse the rejection of claims 6-9 and 13-21 under 35 U.S.C. §
112, first paragraph, as lacking enablement.

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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