Ex Parte Dalencon et al

Board of Patent Appeals and Interferences

Jul 11, 2012

11338908 (B.P.A.I. Jul. 11, 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.
11/338,908 01/24/2006 Francois Dalencon 05-301-A 6024
20306 7590 07/12/2012
MCDONNELL BOEHNEN HULBERT & BERGHOFF LLP
300 S. WACKER DRIVE
32ND FLOOR
CHICAGO, IL 60606
EXAMINER
LUCAS, ZACHARIAH
ART UNIT PAPER NUMBER
1648
MAIL DATE DELIVERY MODE
07/12/2012 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 BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte FRANCOIS DALENCON and CLAIRE-ANNE SIEGRIST
__________

Appeal 2011-006196
Application 11/338,908
Technology Center 1600
__________

Before FRANCISCO C. PRATS, MELANIE L. McCOLLUM, and
JEFFREY N. FREDMAN, Administrative Patent Judges.

Opinion for the Board filed by Administrative Patent Judge PRATS.

Opinion Dissenting-In-Part filed by Administrative Patent Judge
McCOLLUM.

PRATS, Administrative Patent Judge.

DECISION ON APPEAL
This appeal under 35 U.S.C. § 134 involves claims to the use of 3β-
[N-(N‟,N‟-dimethyl-aminoethane)carbamoyl] cholesterol (“DCchol”) as an
adjuvant in vaccines for newborns. The Examiner rejected the claims both
for lack of enablement and as obvious.
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We have jurisdiction under 35 U.S.C. § 6(b). We affirm the
enablement rejection, but reverse the obviousness rejections.

STATEMENT OF THE CASE
Claims 4, 6, 7, and 9 are currently pending (App. Br. 3). Claims 4, 6,
7, and 9 stand rejected and appealed (id.). Claims 4 and 6 illustrate the
appealed subject matter and read as follows:
4. In a method of enhancing an immune response in a
newborn mammal in which at least one vaccine antigen is
administered to the newborn mammal, the improvement
comprising co-administering at least one adjuvant comprising
3β-[N-(N',N'dimethylaminoethane)carbamoyl]cholesterol, the
amount of 3β-[N-(N',N'-dimethy1-
aminoethane)carbamoyl]cholesterol being sufficient to result in
an enhancement of the immune response to the antigen.

6. The method according to claim 4 where the at least one
vaccine antigen is the TAT antigen of the human
immunodeficiency virus.

The following grounds for rejection are before us on appeal:
(1) Claims 4, 6, 7, and 9, under 35 U.S.C. § 112, first paragraph for
lack of enablement (Ans. 4-8);
(2) Claims 4 and 7, under 35 U.S.C. § 103(a) as obvious over
Semple,
1
Lolekha,
2
and Brunel
3
(Ans. 8-10); and

1
Semple et al., U.S. App. Pub. No. 2003/0125292 A1 (filed Nov. 7, 2002).
2
Somsak Lolekha et al., Protective efficacy of hepatitis B vaccine without
HBIG in infants of HBeAg-positive carrier mothers in Thailand, 20 VACCINE
3739-3743 (2002).
3
F. Brunel et al., Cationic lipid DC-Chol induces an improved and balanced
immunity able to overcome the unresponsiveness to the hepatitis B vaccine,
17 VACCINE 2192-2203 (1999).
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(3) Claims 4, 6, 7, and 9, under 35 U.S.C. § 103(a) as obvious over
Semple, Locher,
4
and Safrit
5
(Ans. 10-11).
ENABLEMENT
The Examiner rejected claims 4, 6, 7, and 9 under 35 USC § 112, first
paragraph, because the Specification,
while being enabling for a method of inducing a immune
response in newborn mice using an antigen and adjuvant
DCchol (a cationic liposome), does not reasonably provide
enablement for a method of immunizing human newborns using
vaccine antigen of HIV TAT and DCchol against HIV, and
does not reasonably provide enablement for the claimed method
of immunizing newborns of all subject using any antigen and
adjuvant DCchol against any infectious diseases.

(Ans. 4 (emphasis removed).)
To interpret the claims, the Examiner looked to the Specification,
which defines “enhancement of the immune response” to mean
the obtaining, in the newborn, of an immune response that is
similar to that obtained in adults; it may in particular be an
antibody response or a T-cell response, which would be
quantitatively increased compared with that generally obtained
with the vaccines of the prior art, or else a qualitative
modification of the response obtained; the qualitative
characteristics of the immune responses possibly being
expressed in terms of the nature of the antibodies produced, and
also in terms of the nature and the amounts of the cytokines
induced, which makes it possible in particular to determine the
Th1 or Th2 orientation of the response.

4
Christopher Locher et al., Human immunodeficiency virus type 2 DNA
vaccine provides partial protection from acute baboon infection, 22
VACCINE 2261-2272 (2004).
5
Jeffrey Safrit et al., Immunoprophylaxis to Prevent Mother-to-Child
Transmission of HIV-1, 35 J. ACQUIR. IMMUNE DEFIC. SYNDR. 169-177
(2004).
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(Spec. 3.) Viewing the Specification‟s definition in light of the dictionary
definitions of “vaccine” and “immunize,” the Examiner interpreted the
claims as encompassing all “prophylactic and therapeutic” uses of a vaccine
in a newborn mammal, “especially humans, for providing immunity against
a pathogen” (Ans. 5).
The Examiner conceded that the Specification exemplified a vaccine
comprising a HIV TAT protein and DCchol adjuvant that generated “higher
total antibody titer in newborn Balb/c mice than the formulations comprising
TAT and adjuvant ALOOH or Emulsion” (id. at 5-6). The Examiner found,
however, that the Specification did not demonstrate that those antibodies
could neutralize HIV or protect the mice from HIV infection, nor did the
Specification describe any vaccine composition that provided “immune
responses against HIV infection, nor against any pathogens, in newborns of
any species” (id. at 6).
To support the position that the results Appellants obtained in mice
were not predictive of the result that would be obtained in other species,
among other references the Examiner cited Pialoux
6
as showing that DCchol
did not potentiate the immune response to HIV antigen gp160 in a human
phase I study (id. at 6; Pialoux at 2663). As Pialoux also described a prior
study showing DCchol increasing the immune response in mice, the
Examiner reasoned that “the results of animal studies do not directly
translate to the same results in humans” (Ans. 6). The Examiner thus
concluded, based on the overall unpredictability in the art of generating

6
Gilles Pialoux et al., Phase 1 study of a candidate vaccine based on
recombinant HIV-1 gp160 (MN/LAI) administered by the mucosal route to
HIV-seronegative volunteers, 26 VACCINE 2657-66 (2008).
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useful vaccines to HIV antigens, that while the Specification was enabling
with respect to mice, it would require a person having ordinary skill in the
art to perform undue experimentation to practice the claimed invention as it
pertained to other animals, including humans (see id. at 6-8).
Appellants argue that the claims only cover the enhancement of an
immune response (App. Br. 4). “Whether immunity is induced is not
relevant to the patentability of the claim because [it] is not a limitation of the
claim” (id.; see also Reply Br. 2-3). Further, Appellants argue, the presence
of one inoperable embodiment does not render the entire claim invalid for
lack of enablement (App. Br. 5). Appellants also contend that since the
Examiner rejected the claims under 35 U.S.C. § 103 as obvious, the claims
must in fact be enabled (id. at 5-6).
We select claim 4 as representative of the rejected claims. See 37
C.F.R. § 41.37(c)(1)(vii).
We agree that claim 4 only requires the practitioner to enhance an
immune response in a newborn mammal. However, as the Examiner points
out, the claim encompasses doing so in any newborn of any mammalian
species, whereas Appellants have only shown that DCchol has an adjuvant
effect in newborn mice (see Spec. 8-10). Moreover, the Examiner has
advanced evidence, undisputed by Appellants as reflecting the level of
unpredictability in the art at the time of filing, that while DCchol may have
had an adjuvant effect in mice, it did not enhance the immunogenic effect of
the HIV gp160 antigen in human subjects (Ans. 6 (citing Pialoux)).
We acknowledge that “[e]ven if some of the claimed combinations
[are] inoperative, the claims are not necessarily invalid.” Atlas Powder Co.
v. E.I. du Pont de Nemours & Co., 750 F.2d 1569, 1576 (Fed. Cir. 1984)
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(emphasis added). But when “the number of inoperative combinations
becomes significant, and in effect forces one of ordinary skill in the art to
experiment unduly in order to practice the claimed invention, the claims
might indeed be invalid.” Id. at 1576-77.
For example, in In re Wright, the Federal Circuit considered the
enablement of claims directed towards “any and all . . . vaccines . . . which
elicit immunoprotective activity in any animal toward any RNA virus.” In
re Wright, 999 F.2d 1557, 1562 (Fed. Cir. 1993). To enable these claims,
Wright advanced one working example. Id.
The examiner rejected certain of Wright‟s claims for lack of
enablement as requiring undue experimentation due to the claims‟ breadth,
the unpredictability in the art, and the limited direction provided by the
disclosure. Id. at 1560. The examiner cited a journal article demonstrating a
high level of uncertainty and unpredictability in the art of making vaccines
against HIV in humans, the article notably teaching that vaccine efficacy in
animal models did not correlate directly to humans. Id. As Wright was
unable to provide sufficient evidence to rebut the assertion of undue
experimentation, the court affirmed the examiner‟s rejection. Id. at 1564.
Similarly, in the instant case claim 4 recites a method for enhancing
an immune response in any newborn mammal, including humans, using
DCchol as an adjuvant. Like the applicant in Wright, Appellants‟ working
examples are limited to a single species, mice (see Spec. 7-9). Like the
examiner in Wright, the Examiner has advanced evidence, in the instant case
undisputed by Appellants, to show unpredictability in the correlation
between the claimed adjuvant‟s effectiveness in mice as compared to
humans (Ans. 6 (citing Pialoux)).
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Thus, given the evidence that DCchol‟s adjuvant activity in mice does
not predictably correlate to similar activity in humans, and given that the
Specification does not contain any data showing DCchol‟s effectiveness in
newborn humans or other animals, nor is there any such evidence on the
record, we agree with the Examiner that the use of DCchol as an adjuvant in
newborn humans and other non-mouse animals, encompassed by claim 4, is
not enabled. Accordingly, we affirm the Examiner‟s enablement rejection of
claim 4, as well as claims, 6, 7, and 9, which were not argued separately.
OBVIOUSNESS
The Examiner also rejected claims 4 and 7 as obvious over Semple,
Lolekha, and Brunel (Ans. 8-10). The Examiner cited Semple as teaching
administration of a DCchol-containing hepatitis B virus vaccine (HBV) to
neonates, that is, newborns under 1 month old (id. at 8 (citing Semple
[0251]-[0252]). The Examiner noted that Lolekha similarly disclosed that it
was known in the art to immunize neonates and infants with HBV vaccine
(id. at 9), and further noted Brunel‟s teaching that, when administered in a
mouse model as an adjuvant with hepatitis B antigen, DCchol overcame the
unresponsiveness of the mice to the antigen by itself (id.).
Based on the references‟ teachings, the Examiner concluded that “it
would have been obvious to one of ordinary skill in the art at the time the
invention was made to use DCchol as an adjuvant with an HBV vaccine for
immunizing an infant or a newborn mammal” (id.).
“In rejecting claims under 35 U.S.C. § 103, the examiner bears the
initial burden of presenting a prima facie case of obviousness. Only if that
burden is met, does the burden of coming forward with evidence or
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argument shift to the applicant.” In re Rijckaert, 9 F.3d 1531, 1532 (Fed.
Cir. 1993).
As noted above, the Examiner concludes that while the Specification
enables a process of using DCchol to enhance an immune response in
newborn mice, the Specification does not enable such a process in newborn
humans (see Ans. 4). Thus, in maintaining the obviousness rejection despite
this position, the Examiner urges that “the scope of the claims also
encompasses the enable[d] embodiment of enhancing the immune response
to TAT antigen and DCchol in animals, such as mice or macaques” (Ans.
18).
We are not persuaded, however, that the Examiner has adequately
explained why the cited references would have prompted an ordinary artisan
to use DCchol as an adjuvant in newborn mice, to which the Examiner limits
enablement in the rejection under 35 U.S.C. 112, first paragraph.
We acknowledge that Semple and Lolekha both disclose the
importance of protecting human infants from HBV (see Semple [0252];
Lolekha 3739 (abstract)). The Examiner has not, however, explained why
such teachings suggesting the importance of protecting human infants from
HBV would have prompted of an ordinary artisan to administer a DCchol-
potentiated HBV vaccine to a newborn mouse. Nor has the Examiner
provided any other logical rationale as to why an ordinary artisan would
have considered it obvious to immunize newborn mice against HBV with a
DCchol-potentiated vaccine.
Thus, as the Examiner has not identified any disclosure in any of the
cited references explaining why an ordinary artisan would have been
prompted to administer a DCchol-potentiated HBV vaccine to a newborn
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mouse, and as the Examiner had advanced no reasonable alternative
rationale explaining why an ordinary artisan would have done so, we are not
persuaded that the Examiner has made out a prima facie case of obviousness
as to claims 4 and 7. We therefore reverse the Examiner‟s obviousness
rejection of those claims over Semple, Lolekha, and Brunel.
The Examiner also rejected claims 4, 6, 7, and 9 as obvious over
Semple, Locher, and Safrit (Ans. 10-11). The Examiner again relied on
Semple as disclosing the use of a DCchol-containing adjuvant to boost the
immune response to an antigen, and noted that one suitable antigen
described by Semple was HIV (id. at 10).
The Examiner relied on Locher as describing the use of the TAT
antigen, recited in claims 6 and 9 as the immunizing agent for HIV, noting
that “the method has resulted in partial protection of baboons from
infection” (id.). The Examiner relied on Safrit as teaching that the art
recognized a “need to develop immunoprophylaxis to prevent mother-to-
child transmission of HIV, begun at birth” and noted that had tested such
methods “in a neonatal macaque model within 5 days of birth” (id. at 10-11).
Based on the references‟ teachings, the Examiner reasoned:

The skilled artisan would have been motivated to use DCchol
as an adjuvant in combination with HIV antigen Tat to enhance
immune response in newborns, and would have a reasonable
expectation of success, given that adjuvant DCchol and an
antigen can be used for immunizing a newborn as taught by
Semple, and also given that Tat and can induce an immune
response in a baboon animal model, as taught by Locher. Thus,
the invention as a whole was clearly prima facie obvious to one
of ordinary skill in the art at the time the invention was made.

(Id. at 11.)
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We reverse this rejection as well. As noted above, the Examiner
concluded that Appellants‟ Specification only enabled a process “of
inducing a[n] immune response in newborn mice using an antigen and
adjuvant DCchol” (Ans. 4 (emphasis removed)). In the instant rejection, as
with the obviousness rejection discussed above, we are not persuaded that
the Examiner has advanced an adequate fact-based or logic-based rationale
as to why an ordinary artisan would have been prompted to immunize
newborn mice against HIV.
It might be true that immunizing baboons with a nucleic acid
construct including the gene encoding the TAT antigen was found to confer
partial protection against HIV challenge (see Locher, abstract). It might also
be true that mother to child transmission of HIV was recognized as being of
great concern (Safrit 169 (abstract)), and that passive transfer of certain
monoclonal antibodies was shown to protect against infection in a neonatal
macaque or rhesus monkey model (id. at 170-71).
The Examiner has not explained, however, how or why an ordinary
artisan would have been prompted by these teachings to administer a vaccine
containing the TAT antigen combined with DCchol to a newborn mouse, the
organism to which the Examiner limits enablement. Thus, as we are not
persuaded that the Examiner has adequately explained why an ordinary
artisan would have administered a vaccine containing the TAT antigen
combined with DCchol to a newborn mouse, we conclude that the Examiner
has not made out a prima facie case of obviousness. We therefore also
reverse the Examiner‟s rejection of claims 4, 6, 7, and 9 over Semple,
Locher, and Safrit.
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SUMMARY
We affirm the Examiner‟s rejection of claims 4, 6, 7, and 9 under 35
U.S.C. § 112 first paragraph for lack of enablement with respect to humans.
We reverse the Examiner‟s rejection of claims 4 and 7 under 35
U.S.C. § 103 as obvious over Semple, Lolekha, and Brunel.
We also reverse the Examiner‟s rejection of claims 4, 6, 7, and 9
under 35 U.S.C. § 103 as obvious over Semple, Locher, and Safrit.

AFFIRMED

cdc

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McCOLLUM, Administrative Patent Judge, dissenting-in-part.

I disagree with my colleagues that the obviousness rejections should
be reversed.
With regard to each of the obviousness rejections, I select claim 4 as
representative. Semple discloses that “lipid-nucleic acid („LNA‟)
formulations associated with a target antigen stimulate enhanced mucosal
immune responses directed to that target antigen in vivo, as compared to the
target antigen alone or mixed with the free or unencapsulated form of the
nucleic acids” (Semple, ¶ [0012]). Thus, Semple discloses:
a method for stimulating an enhanced mucosal immune
response in a mammal comprising administering to the
mammal an effective amount of an immunostimulatory
composition comprising an LNA formulation in combination
with at least one antigen, where the LNA formulation
comprises: a) a lipid component comprising at least one lipid;
and b) a nucleic acid component comprising at least one
oligonucleotide, wherein the immunostimulatory composition
stimulates an increased production of IgA as compared to the
free form of the oligonucleotide, in vivo.
(Id. at ¶ [0014].) Semple also discloses that the lipid component may
comprise DC-Chol (id. at ¶ [0018]) and that “examples of antigens include,
but are not limited to, HBA-hepatitis B antigen (recombinant or otherwise);
other hepatitis peptides; [and] HIV proteins GP120 and GP160” (id. at
¶ [0200]). In addition, Semple discloses that the “methods of the present
invention can be used for immunizing an infant by administering to an infant
an immunostimulatory composition of the present invention in an effective
amount for inducing cell mediated immunity in the infant” (id. at ¶ [0251]).
The Specification defines newborns as “infants that are at most one
month old at the time that they receive the first injection” (Spec. 2: 22-25).
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However, in each obviousness rejection, the Examiner provides evidence
that it was known in the art to administer a vaccine antigen to a mammal
within its first month of life (Ans. 9 & 10-11). Thus, I conclude that the
Examiner has set forth a prima facie case of obviousness.
Appellants argue that “Semple does not disclose administering a
vaccine antigen in combination with DCchol as an adjuvant” (App. Br. 6
(emphasis removed)). However, claim 4 requires an adjuvant comprising
DCchol. Appellants have not adequately explained why this language does
not encompass an LNA comprising DCchol as a lipid component.
Appellants also argue that Semple does not teach use of its method on
newborns (id. at 7). While I agree that Semple does not teach administering
its composition to newborns, I do not find the language in Semple‟s
paragraph [0252] clear enough to consider it a teaching away from
newborns. In addition, in each rejection, the Examiner provides additional
evidence to support the conclusion that it would have been obvious to
administer vaccine antigens to newborns (Ans. 9 & 10-11). Appellants have
not adequately explained why this additional evidence fails to overcome this
deficiency in Semple.
In addition, Appellants argue that “the results would be far from
predictable” (App. Br. 8). However, given that Semple specifically teaches
infants, I do not agree that the statements in the Specification noted by
Appellants are sufficient to demonstrate that there would not have been a
reasonable expectation of success with newborns. In addition, I do not find
that Appellants have provided sufficient evidence to demonstrate that the
claimed invention provides unexpectedly superior results, as compared to
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the closest prior art, or of a long felt need, in order to overcome the prima
facie case of obviousness.
Thus, I would affirm both of the obviousness rejections.

DISSENTING-IN-PART