Ex Parte Humphreys et al

Patent Trial and Appeal Board

Apr 15, 2013

11582596 (P.T.A.B. Apr. 15, 2013)

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.
11/582,596 10/18/2006 Robert Humphreys AEX-2002US01 1958
7590 04/15/2013
Kevin M. Farrell
Pierce Atwood
Suite 350
One New Hampshire Avenue
Portsmouth, NH 03801
EXAMINER
KINSEY WHITE, NICOLE ERIN
ART UNIT PAPER NUMBER
1648
MAIL DATE DELIVERY MODE
04/15/2013 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 ROBERT HUMPHREYS, DOUGLAS MACMILLAN POWELL,
and JOHN ZINCKGRAF
__________

Appeal 2012-000374
Application 11/582,596
Technology Center 1600
__________

Before DONALD E. ADAMS, ERIC GRIMES, and MELANIE L.
McCOLLUM, Administrative Patent Judges.

GRIMES, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a method
of increasing the potency of a vaccine, which have been rejected as
anticipated, obvious, and nonenabled. We have jurisdiction under 35 U.S.C.
§ 6(b). We affirm the rejections based on prior art but reverse the rejection
for nonenablement.
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STATEMENT OF THE CASE
The Specification states that the invariant chain (Ii) protein blocks
antigenic peptide binding sites of newly synthesized MHC class II
molecules, preventing them from binding endogenous antigenic peptides
(Spec. 1-2, ¶ 3). “Complexes of MHC class II molecules and Ii protein are
transported from the endoplasmic reticulum to a post-Golgi compartment
where Ii is released by proteolysis after which a specific antigenic peptide
binds to the MHC class II molecule. MHC class II molecules bind only
exogenous antigens, internalized via endocytosis.” (Id.)
The Specification states that application “11/033,039[1] disclose[s] . . .
that an MHC Class II-restricted antigenic epitope which is covalently linked
to a mammalian Ii-Key peptide by an appropriate intervening chemical
structure, forming a hybrid polypeptide, is presented to T lymphocytes by
antigen presenting cells with significantly higher efficacy than is the
precursor antigenic epitope” (id. at 2, ¶ 5). “Ii-Key” is the immuno-
regulatory motif within the Ii protein (id. at 9, ¶ 33).
Claims 1-4 and 6-23 are on appeal. Claims 1, 8, and 19 are
representative and read as follows:
1. A method for increasing the potency of a vaccine directed toward a
pathogen of interest in a subject, the method comprising:
a) providing a vaccine, the vaccine comprising an epitope-containing
protein or portion thereof which is encoded by the genome of the
pathogen, or a DNA encoding the same;
b) providing an Ii-key hybrid construct comprising:
i) the LRMK residues of Ii-key protein; and

1 Application 11/033,039 corresponds to the Humphreys ‘947 publication
relied on by the Examiner.
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ii) an MHC class II epitope contained within the protein or portion
thereof of step a); or;
iii) DNA encoding the elements of i) and ii);
c) priming the immune system of the subject by administering the Ii-key
construct of step b) under conditions appropriate for the stimulation of
an immune response in the subject; and
d) administering the vaccine of step a) under conditions appropriate to
boost the immune response of step c) thereby increasing the potency
of the vaccine relative to a non-primed administration.

8. The method of Claim 1 wherein the subject is a bird.

19. The method of Claim 1 wherein the pathogen is HIV.

The claims stand rejected as follows:
• Claims 19-23 under 35 U.S.C. § 112, first paragraph, for lack of
enablement (Answer 5);
• Claims 1, 2, 4, 6, and 7 under 35 U.S.C. § 102(b) as anticipated by
Humphreys ‘5942 (Answer 8);
• Claims 1, 2, 4, 6, 7, and 10-18 under 35 U.S.C. § 102(e) as
anticipated by Humphreys ‘9473 (Answer 11);
• Claims 3, 8-18, 22, and 23 under 35 U.S.C. § 103(a) as obvious
based on Humphreys ‘594, Kotsopoulou,4 Kallinteris,5 Humphreys
(PharmaDD),6 and Hackett7 (Answer 14); and

2 Humphreys et al., US 2003/0235594 A1, Dec. 25, 2003.
3 Humphreys et al., US 2006/0002947 A1, Jan. 5, 2006.
4 Kotsopoulou et al., A Rev-Independent Human Immunodeficiency Virus
Type 1 (HIV-1)-Based Vector That Exploits a Codon-Optimized HIV-1 gag-
pol Gene, 74 J. VIROL. 4839-4852 (2000).
5 Kallinteris et al., Ii-Key/MHC class II epitope hybrid peptide vaccines for
HIV, 21 VACCINE 4128-4132 (2003).
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• Claims 3, 8, 9, 22, and 23 under 35 U.S.C. § 103(a) as obvious
based on Humphreys ‘947 and Kotsopoulou (Answer 17-18).
I.
The Examiner has rejected claims 19-23 under 35 U.S.C. § 112, first
paragraph, on the basis that the Specification does not provide sufficient
guidance to enable those skilled in the art to make and use an HIV vaccine
(Answer 5-8). The Examiner finds that the term “vaccine” implies a
preparation that provides actual protection from infection, not just increasing
immune responses (id. at 6); that no HIV vaccine exists and developing one
involves inherent difficulties (id.); that the Specification’s working examples
do not show actual protection from HIV infection (id. at 7); and that the state
of the art in HIV vaccine development is unpredictable (id. at 8). The
Examiner therefore concludes that undue experimentation would be required
to practice the claimed method (id.).
Appellants argue that those skilled in the art do not require a
preparation to provide complete protection to qualify as a “vaccine” (Appeal
Br. 4-5) and that the “invention is directed towards ‘increasing the potency’
. . . of a vaccine and not directed towards providing ‘complete protection’”

6 Humphreys et al., Synthetic Peptide Vaccine Against Pandemic H5N1
Influenza Based on Li-Key Modifies MHC Class II Epitopes, PHARMADD,
May/June 2006,
www.pharmadd.com/archives/May_16_2006/BN%20Tech%20Brief.asp
(accessed Dec. 27, 2006).
7 Hackett et al., Immunogenic Peptides of Influenza Virus Subtype N1
Neuraminidase Identify a T-Cell Determinant Used in Class II Major
Histocompatibility Complex-Restricted Responses to Infectious Virus, 65 J.
VIROL. 672-676 (1991).
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(id. at 6). Appellants “submit that the pending specification provides
adequate working examples to support the presently pending claims” (id.)
and that “it would not require undue experimentation to practice the
invention as claimed in pending Claims 19-23” (id. at 7).
We agree with Appellants that the Examiner has not provided an
adequate basis for concluding that practicing the method defined by claims
19-23 would require undue experimentation. As Appellants pointed out, the
claims are not directed to a vaccine against HIV or a method of vaccinating
against HIV. Claim 19 is directed to a “method for increasing the potency of
a vaccine directed toward a pathogen of interest in a subject” (claim 1),
“wherein the pathogen is HIV” (claim 19). Thus, the claims do not require
generating an immune response that provides complete protection, or any
specific degree of protection, from HIV infection, only that the potency of
an HIV vaccine is increased relative to vaccination with an HIV antigen
alone.
The Examiner acknowledges that the “specification contains examples
showing the immunogenicity of the HIV gag protein” (Answer 7).
Appellants state that “paragraphs [0015] and [0070] and Figure 2 of the
pending specification ‘demonstrate that T cell responses can be further
improved by priming with Ii-Key peptides’ and ‘revealed IFN-gamma
responses that were approximately two-fold stronger that [sic] either of the
DNA vaccine regimes’” (Appeal Br. 6). The Examiner does not dispute this
characterization of the Specification’s data.
In short, the nonenablement rejection is based upon a requirement to
obtain results – clinically effective protection from HIV infection – that are
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not required by the claims on appeal. The Examiner has not provided
evidence or persuasive technical reasoning to show that a person of ordinary
skill in the art would have expected that practicing the method defined by
claim 19, to produce the results recited in the claim, would have required
undue experimentation.
II.
Issue
The Examiner has rejected claims 1, 2, 4, 6, and 7 as anticipated by
Humphreys ‘594 (Answer 8), and has rejected claims 1, 2, 4, 6, 7, and 10-18
as anticipated by Humphreys ‘947 (Answer 11). Humphreys ‘947 is a
continuation-in-part of Humphreys ‘594 (Humphreys ‘947, front page), the
Examiner relies on the same disclosures in both references in rejecting claim
1, and Appellants present the same argument in response to both rejections.
We will therefore address them together.
The Examiner finds that both Humphreys references disclose hybrid
peptides comprising the LRMK core motif from the Ii-Key peptide, coupled
to an MHC class II epitope (Answer 9, 12). The Examiner also finds that
both Humphreys references state “that ‘this invention relates to the use of Ii-
Key/antigenic epitope hybrids to enhance protective immune responses to a
subsequently administered DNA vaccine or against an attenuated pathogen
vaccine’” (id. at 10, 13). The Examiner concludes that both Humphreys
references teach “that priming the immune system with the Ii-key/antigen
hybrid peptide followed by administration of the antigen (e.g., protein
antigen or DNA encoding the antigen) will result in an enhanced immune
response” (id.).
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Appellants contend that neither Humphreys reference provides
sufficient guidance to enable a person of ordinary skill in the art to practice
the instantly claimed invention “without the teachings of the presently
pending application” (Appeal Br. 8, 11).
The issue with respect to this rejection is: Have Appellants shown
that the Humphreys references are not enabling for increasing the potency of
a vaccine directed to a pathogen?
Findings of Fact
1. Both Humphreys references disclose “an antigen presentation
enhancing hybrid polypeptide which includes three elements”: (1) “an
N-terminal element consisting essentially of 4-16 residues of the mammalian
Ii-Key peptide,” (2) a polypeptide that binds to the antigenic peptide binding
site of an MHC class II molecule, and (3) “a chemical structure covalently
linking the N-terminal element . . . to the MHC Class II-presented epitope.”
(Humphreys ‘594, ¶ 7; Humphreys ‘947, ¶ 8.)
2. Both Humphreys references disclose that “modified Ii key peptides
which retain antigen presentation enhancing activity will function in the
enhancing hybrid of the present invention. . . . Examples of modified
versions of Ii key peptide which are known to retain high activity are
LRMK,” among others. (Humphreys ‘594, ¶ 28; Humphreys ‘947, ¶ 29.)
3. Both Humphreys references disclose “the use of Ii-Key/antigenic
epitope hybrids to enhance protective immune responses to a subsequently
administered DNA vaccine or against an attenuated infectious pathogen
vaccine. Such adjuvant vaccine preparations can be referred to as
PreVaccinesTM.” (Humphreys ‘594, ¶ 114; Humphreys ‘947, ¶ 115.)
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4. Both Humphreys references disclose that,
[i]n the case of smallpox vaccination, Ii-Key antigenic epitope
hybrids are used to elicit a Th1 response to one or more MHC
Class II-presented epitopes of the gp42 extracellular envelope
protein coded by the B5R viral gene of vaccinia. Individuals so
vaccinated will have an anamnestic response which is more
rapid and of higher potency in terms of antibody titers . . . to
challenge by cDNA vaccines for the B5R gene.
(Humphreys ‘594, ¶ 114; Humphreys ‘947, ¶ 115.)
Analysis
Both Humphreys references disclose a method meeting all of the
limitations of claim 1. The disclosed method includes providing a vaccine
comprising a pathogen protein or DNA (FF3, FF4), providing an Ii-Key
hybrid peptide comprising the LRMK residues of Ii-Key (FF2) and an MHC
Class II epitope from the pathogen’s protein (FF4), priming the immune
system with the hybrid protein (FF3), and administering the vaccine under
conditions that boost the immune response of the subject to the vaccine
(FF4).
Appellants argue, however, that “one of skill in the art would not
have been able at the time of filing to practice the present invention without
undue experimentation in view of the cited Humphreys publication[s]
without the teachings of the presently pending application” (Appeal Br. 8,
11). Appellants do not identify any specific teachings in the present
Specification that would provide the guidance allegedly missing from the
Humphreys references. Instead, Appellants present an analysis of the
Humphreys references based on the factors of In re Wands, 858 F.2d 731,
737 (Fed. Cir. 1988) (Appeal Br. 9-13).
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Appellants’ argument is not persuasive. “[A] prior art publication
cited by an Examiner is presumptively enabling barring any showing to the
contrary by a patent applicant.” In re Antor Media Corp., 689 F.3d 1282,
1288 (Fed. Cir. 2012). “As long as an examiner makes a proper prima facie
case of anticipation by giving adequate notice under § 132, the burden shifts
to the applicant to submit rebuttal evidence of nonenablement.” Id. at 1289.
Appellants’ Wands analysis of the Humphreys references is not
supported by citation to evidence showing that the references do not provide
adequate guidance to enable one skilled in the art to enhance the potency of
a vaccine by carrying out the steps recited in claim 1, which are the same
steps recited in both Humphreys references. Appellants’ unsupported
attorney argument is not “rebuttal evidence of nonenablement,” In re Antor
Media Corp., 689 F.3d at 1289, and therefore is inadequate to show that the
Humphreys references are not enabling for the method of claim 1.
Appellants also argue that the Humphreys references do not specify
“whether the MHC Class II epitope contained within the Ii-Key construct is
necessarily the same epitope encoded by the DNA vaccine. . . . [T]he subject
application specifically requires that the Ii-Key MHC Class II epitope is the
same as the MHC Class II epitope contained within the vaccine protein.”
(Appeal Br. 9, 12.)
This argument is also unpersuasive. Both Humphreys references
expressly describe a method of priming a subject’s immune system using an
Ii-Key hybrid protein comprising the gp42 envelope protein encoded by the
B5R viral gene, which produces a response of “higher potency in terms of
antibody titers . . . to challenge by cDNA vaccines for the B5R gene” (FF4).
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The references therefore describe a method that includes the disputed
limitation.
Conclusion of Law
Appellants have not shown that the Humphreys references are not
enabling for increasing the potency of a vaccine directed to a pathogen. We
affirm the rejection of claim 1 as anticipated by both Humphreys ‘594 and
Humphreys ‘947. Claims 2, 4, 6, 7, and 10-18 were not argued separately
and therefore fall with claim 1. 37 C.F.R. § 41.37(c)(1)(vii).
III.
Issue
The Examiner has rejected claims 3, 8-18, 22, and 23 as obvious
based on Humphreys ‘594, Kotsopoulou, Kallinteris, Humphreys
(PharmaDD), and Hackett (Answer 14); and has rejected claims 3, 8, 9, 22,
and 23 as obvious based on Humphreys ‘947 and Kotsopoulou (Answer 17-
18). The claims subject to each rejection have not been argued separately
and therefore stand or fall together. 37 C.F.R. § 41.37(c)(1)(vii). We select
claim 8 as representative of the claims subject to each of the § 103
rejections.
Claim 8 is directed to the method of claim 1, where the subject treated
is a bird. The Examiner finds that “it is well within the purview of one of
ordinary skill in the art to choose a subject in need of immunization (e.g.,
humans, birds, etc.)” (Answer 17, 18), and therefore the additional limitation
of claim 8 would have been obvious to a person of ordinary skill in the art.
Appellants argue that the Examiner
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has not shown why one of skill in the art would have combined
these techniques without the benefit of the teachings of the
present invention or how one of skill in the art would have
predicted the success of the pending invention based solely in
the identification of these disparate techniques without the
benefit of the teachings of the present invention.
(Appeal Br. 14, 17.)
Appellants have not, however, provided evidence or sound technical
reasons why a person of ordinary skill in the art would not have considered
it obvious to practice the method disclosed by the Humphreys references on
a subject that was a bird. We note that both Humphreys references describe
their methods as applicable to a wide variety of diseases: “an infectious
disease caused or associated with infection by a bacterium, a virus, a
parasite, a fungus, a rickettsia, or other infectious agent” (Humphreys ‘594,
¶ 76; Humphreys ‘947, ¶ 77). In addition, Humphreys (PharmaDD)
describes H5N1 influenza as a virus with “serious pandemic potential” and
refers to it as “bird flu” (Humphreys (PharmaDD), at 4). The evidence of
record thus supports the Examiner’s conclusion that it would have been
obvious to practice the method disclosed by Humphreys ‘594 and
Humphreys ‘947 on a subject that was a bird, for example in order to limit
the spread of H5N1 bird flu.
SUMMARY
We reverse the rejection of claims 19-23 for lack of enablement.
We affirm the rejection of claims 1, 2, 4, 6, and 7 as anticipated by
Humphreys ‘594, and the rejection of claims 1, 2, 4, 6, 7, and 10-18 as
anticipated by Humphreys ‘947.
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We affirm the rejection of claim 8 under 35 U.S.C. § 103(a) as
obvious based on the combination of Humphreys ‘594, Kotsopoulou,
Kallinteris, Humphreys (PharmaDD), and Hackett. Claims 3, 9-18, 22, and
23 fall with claim 8 because they were not argued separately. 37 C.F.R.
§ 41.37(c)(1)(vii).
We affirm the rejection of claim 8 under 35 U.S.C. § 103(a) as
obvious based on Humphreys ‘947 and Kotsopoulou. Claims 3, 9, 22, and
23 fall with claim 8 because they were not argued separately. 37 C.F.R.
§ 41.37(c)(1)(vii).
TIME PERIOD FOR RESPONSE
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-IN-PART

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