Ex Parte Fritz et al

Board of Patent Appeals and Interferences

Mar 21, 2012

10399442 (B.P.A.I. Mar. 21, 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.
10/399,442 04/17/2003 Jorg Fritz I0422.70011US00 9857
23628 7590 03/22/2012
WOLF GREENFIELD & SACKS, P.C.
600 ATLANTIC AVENUE
BOSTON, MA 02210-2206
EXAMINER
DIBRINO, MARIANNE
ART UNIT PAPER NUMBER
1644
MAIL DATE DELIVERY MODE
03/22/2012 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 JORG FRITZ, FRANK MATTNER, WOLFGANG ZAUNER,
ESZTER NAGY, and MICHAEL BUSCHLE
__________

Appeal 2010-011509
Application 10/399,442
Technology Center 1600
__________

Before ERIC GRIMES, LORA M. GREEN, 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 a
vaccine and pharmaceutical composition. The Patent Examiner rejected the
claims as obvious and on the ground of non-statutory obviousness-type
double patenting. We have jurisdiction under 35 U.S.C. § 6(b). We affirm.

Appeal 2010-011509
Application 10/399,442

2
STATEMENT OF THE CASE
Claims 22-28, 37-39, and 45 are on appeal. Claim 22 is representative
and reads as follows:
22. A vaccine comprising at least one antigen and at least one peptide
comprising a sequence R1-XZXZNXZX-R2, wherein:
N is a whole number between 3 and 7;
X is a positively charged natural and/or non-natural amino
acid residue;
Z is an amino acid residue further defined as L, V, I, F and/or W; and
R1 and R2 are independently -H, -NH2, -COCH3, -COH, a peptide
with up to 20 amino acid residues, a peptide reactive group, a
peptide linker with or without a peptide, and wherein X-R2 may
also be an amide, ester, or thioester of the C-terminal amino
acid residue;
wherein upon introduction of the vaccine to a patient the peptide enhances
an adaptive immune response to the antigen in the patient.

The Examiner rejected the claims as follows:
1

• claims 22-28 and 45 under 35 U.S.C. § 103(a) as unpatentable over
Cho
2
and Chertov;
3

• claims 22-28 and 45 under 35 U.S.C. § 103(a) as unpatentable over
Cho and Yang;
4

1
The Examiner withdrew the rejection of claims 22-28, 37-39, and 45 under
35 U.S.C. § 112, first paragraph, as failing to satisfy the written description
requirement, and the rejection of claims 22-28, 37-39, and 45 provisionally
for obviousness-type double patenting over claims 69, 71-72, 75, and 76 of
Application Ser. No. 10/564,429. (Ans. 2-3.)
2
Jang-Hyun Cho et al., Activation of human neutrophils by a synthetic anti-
microbial peptide, KLKLLLLLKLK-NH2, via cell surface calreticulin, 266
EUR. J. BIOCHEM. 878-885 (1999).
3
Patent Application Publication No. US 2002/0072495 A1 by Oleg Chertov
et al., published Jun. 13, 2002.
Appeal 2010-011509
Application 10/399,442

3
• claims 22-28, 37-39, and 45 under 35 U.S.C. § 103(a) as
unpatentable over Cho, Chertov, Weiner,
5
Oxenius,
6
and Fikes;
7

• claims 22-28, 37-39, and 45 under 35 U.S.C. § 103(a) as
unpatentable over Cho, Yang, Weiner, Oxenius, and Fikes; and
• claims 22-28, 37-39, and 45 provisionally on the ground of non-
statutory obviousness-type double patenting as unpatentable over claims 13-
22 of Application Ser. No. 10/550,754 (Buschle application).
8

OBVIOUSNESS
The Issue
The Examiner’s position is that Cho taught the peptide
KLKLLLLLKLK-NH2 (the “L5” peptide) and its D-enantiomer showed
significant chemotherapeutic activity when administered to mice. (Ans. 4.)
The Examiner found that Cho taught that the chemotherapeutic activity was
related to the peptide’s neutrophil-activating activity. (Id.) The Examiner
also found that Cho taught that chemical compounds that activate

4
De Yang et al., LL-37, the Neutrophil Granule- and Epithelial cell-derived
Cathelicidin, Utilizes Formyl Peptide Receptor-like 1 (FPRL1) as a
Receptor to Chemoattract Human Peripheral Blood Neutrophils, Monocytes,
and T Cells, 192 J. EXP. MED. 1069-1074 (2000).
5
George J. Weiner et al., Immunostimulatory oligodeoxynucleotides
containing the CpG motif are effective as immune adjuvants in tumor
antigen immunization, 94 PROC. NATL. ACAD. SCI. 10833-10837 (1997).
6
Annette Oxenius et al., CpG-Containing Oligonucleotides are Efficient
Adjuvants for Induction of Protective Antiviral Immune Responses with T-
Cell Peptide Vaccines, 73 J. VIROLOGY 4120-4126 (1999).
7
Patent Application Publication No. WO 95/04542 by John D. Fikes et al.,
published Feb. 16, 1995.
8
Patent Application Publication No. 2006/0263386 A1 by Michael Buschle
et al., published Nov. 23, 2006.
Appeal 2010-011509
Application 10/399,442

4
neutrophils, such as the L5 peptide, are potentially useful as drugs for
infectious disease. (Id.) Additionally, the Examiner found that Cho taught
that the L5 peptide exhibits anti-bacterial and anti-fungal activity. (Id. at 4-
5.) However, the Examiner found that Cho did not teach using the L5
peptide in a vaccine or pharmaceutical composition comprising at least one
antigen. (Id. at 5.)
The Examiner found that Chertov disclosed a vaccine comprising the
anti-microbial peptide LL-37 and an antigen, wherein the LL-37 peptide acts
as an adjuvant by enhancing the immune response to the vaccine antigen.
(Id.) The Examiner also found that Chertov disclosed that LL-37 has
neutrophil-activating activity.
The Examiner found that Yang taught an anti-microbial peptide LL-
37, from a cathelicidin protein, having neutrophil-activating activity. (Id. at
6.) Additionally, the Examiner found that Yang taught another anti-
microbial peptide, human neutrophil-α-defensin, is chemotactic for human
peripheral blood CD4/CD45RA and CD8 T cells, as well as immature
dendritic cells and when this peptide is administered with protein antigens, it
can promote antigen-specific immune responses. (Id.) The Examiner also
found that Yang taught “that defensins and cathelicidins represent two major
types of endogenous anti-microbial antibiotic peptides and their contribution
to innate host defense against microbial invasion is well established.” (Id.)
Yang also taught defensins contribute to adaptive immunity by alarming the
adaptive immune system, and that LL-37 is predicted to have the same
capacity to augment innate and adaptive host defenses. (Id. at 6-7.)
Regarding the rejections over combinations including Cho and
Chertov, the Examiner concluded that it would have been obvious to a
Appeal 2010-011509
Application 10/399,442

5
person of ordinary skill in the art at the time the invention was made to make
a vaccine composition comprising the neutrophil-activating anti-microbial
L5 peptide taught by Cho with a peptide antigen that is a microbial antigen,
as suggested by Chertov’s disclosure of a vaccine comprising a neutrophil-
activating anti-microbial peptide, i.e., LL-37 and a bacterial or other
microbial antigen. (Id. at 5.) According to the Examiner, an artisan would
have been motivated to do so to make a composition for research for treating
infectious disease. (Id.)
Regarding the rejections over combinations including Cho and Yang,
the Examiner concluded that it would have been obvious to a person of
ordinary skill in the art at the time the invention was made to have used the
neutrophil-activating anti-microbial peptide and chemotherapeutic peptide
taught by Cho in combination with a protein antigen, e.g., a bacterial vaccine
antigen, as taught by Yang for another anti-microbial peptide. (Id. at 7.)
According to the Examiner, an artisan would have been motivated to do so
to make a composition for research because Cho taught that their anti-
microbial neutrophil-activating peptide is potentially useful as a drug for
infectious disease treatment and Yang taught other anti-microbial peptides
that have a role in non-specifically enhancing an antigen-specific immune
response in combination with protein antigens. (Id.)
Appellants contend that a skilled artisan would not have been
motivated to combine the teachings of Cho and Chertov because their
disclosed peptides “differ in their modes of action as well as in their
biological effects.” (App. Br. 7.) Specifically, Appellants assert that Cho
suggests using L5 as an antimicrobial drug against infectious diseases based
on its teaching that L5 is able to activate human neutrophils for producing
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Application 10/399,442

6
superoxide anion, which is toxic for microbes. (Id. at 7-8.) Appellants
assert that neutrophils are components of innate immunity that are usually
activated at the site of infection in a non-specific manner, e.g., production of
superoxide anion directly killing microbes. (Id.) According to Appellants,
activation of neutrophils would not contribute to the creation of
immunological memory to an immunogen, i.e., influence antigen-specific
activation of adaptive immunity. (Id. at 8.) On the other hand, Appellants
assert that Chertov teaches that the LL-37 peptide stimulates both innate and
adaptive immunity and may be used as an adjuvant when administered in a
vaccine. (Id.) Specifically, Appellants assert that Chertov teaches that LL-
37 (a) activates neutrophils, (b) acts as a chemoattractant on human immune
cells by inducing their chemotactic and Ca2
+
mobilizing activity, and (c)
binds to a specific formyl peptide receptor-like 1 (FPRL1) receptor on the
surface of human leukocytes promoting their migration. (Id.) Therefore, in
view of the different modes of action and biological effects of L5 and LL-
37, Appellants assert that a skilled artisan would not have expected L5 to
enhance an adaptive immune response like LL-37 and therefore would not
have combined the teachings of Cho and Chertov to arrive at the claimed
invention. (Id. at 8-9.)
Appellants also contend that a skilled artisan would not have had a
reason to combine the teachings of Cho and Yang because the artisan would
have also understood from these references that L5 and LL-37 differ in their
modes of action and in their biological effects. (Id. at 11.) In particular,
Appellants assert that while Yang suggests that LL-37 is involved in the
stimulation of both innate and adaptive host response, Cho only teaches that
L5 activates neutrophils. (Id.)
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The issue is whether the preponderance of the evidence supports the
Examiner’s conclusion that the cited references would have made the
claimed vaccine and pharmaceutical composition obvious.
Findings of Fact
1. We agree with the Examiner’s explicit findings regarding the scope
and content of Cho, Chertov, and Yang. (See Ans. 4-7.)
Principles of Law
A conclusion that the claimed subject matter is prima facie obvious
must be supported by evidence, as shown by some objective teaching in the
prior art or by knowledge generally available to one of ordinary skill in the
art that would have led that individual to combine the relevant teachings of
the references to arrive at the claimed invention. See In re Fine, 837 F.2d
1071, 1074 (Fed. Cir. 1988).
Analysis
While we agree with the Examiner’s explicit findings regarding the
scope and content of Cho, Chertov, and Yang, we do not agree with the
Examiner’s conclusion that the combination of Cho and Chertov or the
combination of Cho and Yang would have motivated a skilled artisan to
make a vaccine or pharmaceutical composition comprising an antigen and
Cho’s L5 peptide. The Examiner’s combination in each rejection relies on
the prior art teachings that both L5 and LL-37 exhibit neutrophil-activating
activity. However, what is missing from the Examiner’s conclusion is some
persuasive evidence that this shared activity contributes to the adjuvant
properties of LL-37 as taught by Chertov and Yang. See Fine, 837 F.2d at
1074.
Accordingly, we reverse the Examiner’s obviousness rejections.
Appeal 2010-011509
Application 10/399,442

8

OBVIOUSNESS-TYPE DOUBLE PATENTING
The Examiner rejected claims 22-28, 37-39 and 45 provisionally on
the ground of nonstatutory obviousness-type double patenting because the
conflicting claims had not been issued in a patent at the time of the rejection.
(Ans. 14.) As acknowledged by Appellants (Reply Br. 5) the claims have
since been issued in the Buschle patent.
9
In the Reply Brief, Appellants do
not contest the rejection on the merits but instead state that they “will file a
terminal disclaimer in this case if this is the only remaining rejection against
the claims.” (Id.)
Accordingly, we summarily affirm the obviousness-type double
patenting rejection of the claims on appeal set forth by the Examiner.

CONCLUSION OF LAW
The preponderance of the evidence does not support the Examiner’s
conclusion that the cited references would have made the claimed vaccine
and pharmaceutical composition obvious.

9
Patent No. US 7,704,514 B2, issued to Michael Buschle et al., Apr. 27,
2010.
Appeal 2010-011509
Application 10/399,442

9
SUMMARY
We reverse each of the obviousness rejections;
we affirm nonstatutory obviousness-type double patenting rejection.

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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