Ex Parte Raney et al

Patent Trial and Appeal Board

Apr 19, 2016

12291473 (P.T.A.B. Apr. 19, 2016)

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.
12/291,473 11/10/2008 Kevin D. Raney 110.001US2 9137
66981 7590 04/19/2016
HUGH MCTAVISH
MCTAVISH PATENT FIRM
7460 Pinehurst Road
Pine Springs, MN 55115
EXAMINER
KINSEY WHITE, NICOLE ERIN
ART UNIT PAPER NUMBER
1648
MAIL DATE DELIVERY MODE
04/19/2016 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 KEVIN D. RANEY, CRAIG E. CAMERON,
BHUVANESH DAVE, JOSHUA SAKON, JEFF ZHIQIANG LU,
SAMUEL G. MACKINTOSH, and THOMAS A. JENNINGS
__________

Appeal 2013-010568
Application 12/291,473
Technology Center 1600
__________

Before JEFFREY N. FREDMAN, ULRIKE W. JENKS, and
JACQUELINE T. HARLOW, Administrative Patent Judges.

FREDMAN, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal1 under 35 U.S.C. § 134 involving claims to an
antiviral pharmaceutical composition. The Examiner rejected the claims as
obvious. We have jurisdiction under 35 U.S.C. § 6(b). We affirm.

1 Appellants identify the Real Party in Interest as the Board of
Trustees of the University of Arkansas (see Br. 3).
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Statement of the Case
Background
“[C]ompounds and methods for inhibiting HCV replication are
needed. Methods of identifying compounds that inhibit HCV replication are
also needed” (Spec. 2, l. 31–3, l. 2).
The Claims
Claims 10, 15, 32, and 35–38 are on appeal.2 Independent claim 10 is
representative and reads as follows:
10. A pharmaceutical composition comprising:
a compound of molecular weight 10,000 or less,
wherein the compound interacts with NS3 to inhibit NS3
oligomerization and wherein the compound inhibits hepatitis C
virus (HCV) replication;
wherein the compound consists of SEQ ID NO:l; and
a pharmaceutically acceptable diluent.

The Issues
A. The Examiner rejected claims 10 and 36–38 under 35 U.S.C. § 103(a)
over Sette3 (Ans. 5–10).
B. The Examiner rejected claims 15 and 35 under 35 U.S.C. § 103(a)
over Sette, Kim4, Beerens5, Bishop6, and Arai7 (Ans. 11–14).

2 Claims 1–9, 11–14, 16–31, 33, and 34 were cancelled (Br. 3).
3 Sette et al., WO 01/21189 A1, published Mar. 29, 2001.
4 Kim et al., Introduction of Soluble Proteins into the MHC Class I
Pathway by Conjugation to an HIV tat Peptide, 159 J. IMMUN.
1666–1668 (1997).
5 Beerens et al., Protein Transduction Domains and their Utility in
Gene Therapy, 3 CURRENT GENE THER. 486–494 (2003).
6 Bishop et al., Inhibitors of XRCC3p, PREPARED FOR: U.S. ARMY
MED. RES. & MATERIEL COMMAND (Oct. 2003).
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C. The Examiner rejected claim 32 under 35 U.S.C. § 103(a) over Sette
and Regenmortel8 (Ans. 14–15).
A. 35 U.S.C. § 103(a) over Sette
The issue with respect to this rejection is: Does the evidence of
record support the Examiner’s conclusion that Sette renders claims 10 and
37 obvious?
Findings of fact
1. The Specification teaches “a peptide having the sequence
HIDAHFLSQTK [as] (SEQ ID NO:1)” (Spec. 14, l. 2).
2. The Specification teaches “a peptide comprising the reverse D
analog of SEQ ID NO:1 . . . (or a portion thereof, e.g., at least 4 contiguous
residues), where the amino acids are D isomers instead of L isomers” (Spec.
14, ll. 5–9).
3. Sette teaches that “[t]his invention uses our knowledge of the
mechanisms by which antigen is recognized by T cells to identify and
prepare HCV epitopes, and to develop epitope-based vaccines directed
towards HCV” (Sette, Abstract).
4. Sette teaches that:
there has existed a need for peptide epitopes that are
bound by multiple HLA antigen molecules for use in epitope-
based vaccines. The greater the number of HLA antigen
molecules bound, the greater the breadth of population

7 Arai et al., Design of the linkers which effectively separate
domains of a bifunctional fusion protein, 14(8) PROTEIN
ENGINEERING 529-532 (2001).
8 Regenmortel et al., D-peptides as immunogens and diagnostic
reagents, 9 CURRENT OPINIONS IN BIOTECH. 377–382 (1998).
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coverage by the vaccine . . . Furthermore, as described herein
in greater detail, a need has existed to modulate peptide binding
properties, for example, so that peptides that are able to bind to
multiple HLA antigens do so with an affinity that will stimulate
an immune response . . . [E]pitopes for inclusion in vaccine
compositions of the invention are selected by a process
whereby protein sequences of known antigens are evaluated for
the presence of motif or supermotif-bearing epitopes . . .
Supermotif-bearing peptides may additionally be tested for the
ability to bind to multiple alleles within the HLA supertype
family. The invention also includes an embodiment comprising
a method for monitoring or evaluating an immune response to
HCV in a patient having a known HLA-type, the method
comprising incubating a T lymphocyte sample from the patient
with a peptide composition comprising an HCV epitope
consisting essentially of an amino acid sequence described in
Tables VII to Table XX or Table XXII which binds the product
of at least one HLA allele present in said patient, and detecting
for the presence of a T lymphocyte that binds to the peptide.

(Sette, 6, l. 3 to 7, l. 1).
5. Sette teaches that the “identification of motifs and/or
supermotifs that correlate with high and intermediate affinity binding is an
important issue with respect to the identification of immunogenic peptide
epitopes for the inclusion in a vaccine” (Sette 20, ll. 11–14).
6. Sett teaches that the Kast study “demonstrates the value of
motifs for the identification of peptide epitopes for inclusion in a vaccine:
application of motif-based identification techniques eliminates screening of
90% of the potential epitopes in a target antigen protein sequence. Such
peptide epitopes are identified in the Tables” (Sette 20, ll. 23–27).
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7. Sette teaches that:
To obtain the peptide epitope sequences listed in each
Table, protein sequence data from fourteen HCV isolates were
evaluated for presence of the designated supermotif . . . .
Peptide epitopes were additionally evaluated on the basis of
their conservancy among these fourteen strains . . . . A criterion
for conservancy requires that the entire 9-mer region of an HLA
class II binding peptide be totally conserved in 79% of the
sequences available for a specific protein. The percent
conservancy of the selected peptide epitopes is indicated on the
Tables. The frequency, i.e. the number of strains of the
fourteen strains in which the totally conserved peptide sequence
was identified, is also shown.

(Sette 21, l. 26 to 22, l. 4).
8. Sette teaches that “[t]he HLA-A3 supermotif is characterized by
the presence in peptide ligands of A, L, I, V, M, S, or, T as a primary anchor
at position 2, and a positively-charged residue, R or K, at the C-terminal
position of the epitope” (Sette 23, ll. 21–31).
9. Sette teaches that “[t]he HLA-A3 motif is characterized by the
presence in peptide ligands of L, M, V, I, S, A, T, F, C, G, or D as a primary
anchor residue at position 2, and the presence of K, Y, R, H, F, or A as a
primary anchor residue at the C-terminal position of the epitope . . . .
Peptide epitopes that comprise the A3 motif are set forth in Table XVI.
Peptide epitopes that also comprise the A3 supermotif are also listed in
Table IX” (Sette 27, ll. 25–34).
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10. Table XVI of Sette is reproduced in relevant part below:

(Sette 156).
11. Table IX of Sette is reproduced in relevant part below:

(Sette 119).
12. Sette teaches that “[t]he HLA–A 11 motif is characterized by
the presence in peptide ligands of V, T, M, L, I, S, A, G, N, C, D, or F as a
primary anchor residue in position 2, and K, R, Y, or H as a primary anchor
residue at the C-terminal position of the epitope . . . . Representative peptide
epitopes that comprise the A11 motif are set forth on the attached Table
XVII; peptide epitopes comprising the A3 allele-specific motif are also
present in this Table because of the extensive overlap between the A3 and
A11 motif primary anchor specificities” (Sette 28, ll. 3–10).
13. Table XVII of Sette is reproduced in relevant part below:

(Sette 167).
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Principles of Law
“The combination of familiar elements according to known methods
is likely to be obvious when it does no more than yield predictable results.”
KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007).
Analysis
We adopt the Examiner’s findings of fact and reasoning regarding the
scope and content of the prior art (Ans. 5–10; FF 1–13) and agree that the
claims are rendered obvious by Sette. We address Appellants’ arguments
below.
Appellants contend with respect to claim 10 that
Sette does not disclose any pharmaceutical utility for
SEQ ID NO:1, not even utility as a vaccine (which is disclosed
for other HCV peptides but not HIDAHFLSQTK), and thus
does not disclose or suggest a pharmaceutical composition
comprising HIDAHFSQTK (SEQ ID NO:1) and a
pharmaceutically acceptable diluent, as is recited in claim. 10.
The Examiner’s position is that because SEQ ID NO:l is
disclosed in Sette, even though no pharmaceutical utility,
including any utility as a vaccine, is disclosed for it, that
constitutes an anticipation of a claim to a pharmaceutical
composition comprising the peptide and a pharmaceutically
acceptable diluent . . . . The Examiner concedes that “Sette et
al. is interested in these peptide motifs for the identification of
peptide epitopes (e.g., CTL inducing peptide epitopes) for
inclusion in vaccines (e.g., a pharmaceutical use).” (Page 5 of
Office Action mailed January 17, 2012.) But then she ignores
the fact that Sette rules out this particular peptide for inclusion
in vaccines, because Sette et al. did not include it in Tables
XXVI-XXIX and XXXII, which are the only ones it says are
suitable as vaccines. (Page 45, lines 15–16.) The Examiner
further concedes “Sette et al. . . . does not suggest using this
sequence [SEQ ID NO:1] for immunization or in
pharmaceutical compositions.” (Page 6, of the Office Action
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mailed January 17, 2012). That should be the end of the
analysis. That statement proves that claim 10 is not obvious
over by Sette.

(Br. 7).
We are not persuaded. First, Appellants’ reference to an anticipation
rejection, and to the Examiner’s position in the office action mailed January
17, 2012, are moot as they are not germane to the instant obviousness
rejection and/or the current position taken by the Examiner.9
We find that the evidence supports the Examiner’s position regarding
pharmaceutical utility for SEQ ID NO:1. Sette teaches selecting epitopes for
inclusion in a vaccine by identifying HCV epitopes motifs or supermotifs
(FF 4–6). Sette teaches that “application of motif-based identification
techniques eliminates screening of 90% of the potential epitopes in a target
antigen protein sequence”, and that such desirable “peptides epitopes are
identified in the Tables described below” (FF 6), including Tables IX, XVI
and XVII, which each disclose SEQ ID NO:1 (FF 1, 10, 11, 13).
Sette teaches a “method for monitoring or evaluating an immune
response to HCV in a patient having a known HLA-type . . . with a peptide
composition comprising an HCV epitope consisting essentially of an amino
acid sequence described in Tables VII to Table XX”, wherein, again, Table

9 “There is nothing unusual, certainly, about an examiner changing
his viewpoint as to the patentability of claims as the prosecution of
a case progresses, and, so long as the rules of Patent Office
practice are duly complied with, an applicant has no legal ground
for complaint because of such change in view. The life of a patent
solicitor has always been a hard one.” In re Ruschig, 379 F.2d
990, 993 (CCPA 1967).
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IX discloses SEQ ID NO:1 (FF 11). Sette further teaches that “protein
sequence data from fourteen HCV isolates were evaluated for presence of
the designated supermotif”, and “were additionally evaluated on the basis of
their conservancy among these fourteen strains”, and reports in Table XVI
100% conservancy for SEQ ID NO:1 among all fourteen strains (FF 7, 10).
Sette further identifies SEQ ID NO:1 as having both the HLA-A3 motif (in
Table XVI), the HLA-A3 supermotif (in Table IX), and HLA-A 11 motif (in
Tables XVII) (FF 8–13).
We recognize, but do not find persuasive, Appellants’ contention that
“Sette concerns vaccines against HCV, and discloses that epitopes listed in
Tables XXVI-XXIX and XXXII may be utilized in a vaccine, but the cited
sequence is not in these tables” (Br. 6; emphasis in the original).
While Appellants are correct that Sette did not choose the peptide of
SEQ ID NO:1 for further testing, Sette did specifically identify SEQ ID
NO:1 by computer screening as containing an epitope with the HCV motifs
necessary for inclusion in vaccine compositions (FF 7–13). Each the listed
peptides identified by Sette’s screening would have been expected by Sette
to function as an antigen in a vaccine (FF 4–13). “If a person of ordinary
skill can implement a predictable variation, § 103 likely bars its
patentability.” KSR at 417.
Conclusion of Law
The evidence of record supports the Examiner’s conclusion that Sette
renders claims 10 and 37 obvious.
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B. 35 U.S.C. § 103(a) over Sette, Kim, Beerens, Bishop, and Arai
The issue with respect to this rejection is:
(i) Does the evidence of record support the Examiner’s conclusion
that Sette, Kim, Beerens, Bishop, and Arai render claims 15 and 35 obvious?
(ii) Have Appellants presented evidence of secondary
considerations, that when weighed with the evidence of obviousness, is
sufficient to support a conclusion of non-obviousness?
Findings of Fact
14. Kim teaches that
Protection against most intracellular pathogens requires T
cells that recognize pathogen-derived peptides in association
with MHC class I molecules on the surface of infected cells.
However, because exogenous proteins do not ordinarily
enter the cytosol and access the MHC class I-processing
pathway, protein-based vaccines that induce class I-
restricted CTL responses have proved difficult to design.
We have addressed this problem by conjugating proteins,
such as OVA, to a short cationic peptide derived from HIV-
1 tat (residues 49-57). When APC were exposed in vitro to
such protein conjugates, they processed and presented the
peptides in association with MHC class I molecules and
stimulated CD8+ Ag-specific T cells. Moreover, Ag-
specific CTLs were generated in vivo by immunizing mice
with histocompatible dendritic cells that had been exposed
to protein-tat conjugates.

(Kim, Abstract).
15. Beerens teaches that “[t]he minimal PTD [protein transduction
domain] of TAT has been identified as a 9 amino acid (aa) sequence . . .
(TAT49-57)” (Beerens 487, col. 1).
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16. Beerens teaches that “[s]everal peptides have been synthesized
in attempt to create more potent PTDs . . . . Many of these synthetic PTDs
are based on existing and well documented peptides . . . . A few of these
synthetic PTDs showed better translocation properties then the existing ones.
Some interesting synthetic PTDs are mentioned in Table 2” (Beerens, 488,
col. 2; emphasis in the original).
17. Table 2 of Beerens is reproduced in relevant part below:

(Beerens 488).
18. Bishop teaches “the peptide Rad51C”, wherein in Figure 2B
“[a] three-residue glycine linker connects the RAD51C-derived and peptide
transduction segments” as follows:

(Bishop 6).
19. Dowdy teaches “an anti-pathogen system that kills or injures
pathogen-infected cells by introducing into the cells a fusion protein
comprising a protein transduction domain and a cytotoxic domain” (Dowdy,
col. 1, ll. 16–19).
20. Dowdy teaches a “protein transduction domain . . . wherein the
transduction domain consists of . . . YARAAARQARA (SEQ ID NO. 4)”
(Dowdy, claims 18).
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21. Arai teaches that “linkers can effectively separate the domains
of fusion proteins and the distance between the domains can be controlled by
changing the repetitions” (Arai 531, col. 2).
Analysis
We adopt the Examiner’s findings of fact and reasoning regarding the
scope and content of the prior art (Ans. 11–14; FF 14–21) and agree that the
claims are rendered obvious by Sette, Kim, Beerens, Bishop, and Arai. We
address Appellants’ arguments below.
Appellants contend that
Dowdy provides no motivation to modify Sette by
attaching a protein transduction domain to the present SEQ
ID NO:1 . . . . Dowdy teaches fusing a protein transduction
domain to a cytotoxic domain, not to a peptide for use as a
vaccine, much less to a peptide that has no pharmaceutical
utility. Accordingly, Dowdy provides no suggestion or
motivation to modify Sette to attach Dowdy’s SEQ ID NO:4
to the present SEQ ID NO:l to arrive at the present SEQ ID
NO:2 . . . . Kim only suggests adding a tat translocation
peptide to proteins, not to short peptides. It states that
exogenous proteins do not ordinarily enter the cytosol . . . .
[T]he Examiner has made no comments about Arai and
Applicants cannot see any relevance to it

(Br. 10; emphasis in the original).
We are not persuaded. Appellants provide no reason, based on
evidence, as to why amino acid chain length matters here. While a peptide
is a short amino acid chain (HIDAHFSQTK is 10 amino acids in length),
and a protein is usually a longer amino acid chain, Kim expressly teaches
that TAT assists in translocation of amino acid chains for inducing immune
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response as required by vaccines (FF 14). Bishop evidences that such
transduction segments may be linked to 12 amino acid peptide sequences
(FF 18). Thus, the Examiner relies upon the combination of Kim and
Bishop to demonstrate the desirability of transduction domains for
immunogens such as Sette’s peptide as well as the ability to link
transduction domains to peptides as well as proteins (FF 14, 18). See In re
Merck & Co., Inc., 800 F.2d 1091, 1097 (Fed. Cir. 1986) (“Non-obviousness
cannot be established by attacking references individually where the
rejection is based upon the teachings of a combination of references. . . .
[The reference] must be read, not in isolation, but for what it fairly teaches
in combination with the prior art as a whole.”).
Appellants further provide no support, by way of evidence or
argument, for the statement that “[h]ad a prima facie case of obviousness
been established, it would be rebutted by the unexpected result that the
recited peptide interacts with NS3 to inhibit NS3 oligomerization and
inhibits hepatitis C virus replication” (Br. 11). Appellants have merely
discovered a previously unappreciated property of a prior art composition,
and this does not render the old composition patentably new to the
discoverers. See Atlas Powder Co. v. Ireco, Inc., 190 F.3d 1342, 1347 (Fed.
Cir. 1999). The claiming of an unknown property that is inherently present
in the prior art does not make the present claims patentable. See In re Best,
562 F.2d 1252, 1254 (CCPA 1977).
Conclusion of Law
(i) The evidence of record support the Examiner’s conclusion that
Sette, Kim, Beerens, Bishop, and Arai render claims 15 and 35 obvious.
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(ii) Appellants have not presented evidence of secondary
considerations, that when weighed with the evidence of obviousness, is
sufficient to support a conclusion of non-obviousness.
C. 35 U.S.C. § 103(a) over Sette and Regenmortel
The issue with respect to this rejection is: Does the evidence of record
support the Examiner’s conclusion that Sette and Regenmortel render claim
32 obvious?
Findings of Fact
22. Regenmortel teaches that “[t]here has been a regain of interest
in the immunological applications of peptides assembled partly or totally
from D-amino acids. Such peptides are much more stable to proteolysis than
natural L-peptides and they have considerable potential as synthetic vaccines
and as immunomodulators in T-cell responses” (Regenmortel, Abstract).
23. Regenmortel teaches that retro-all-D
RI peptide analogues of the immunodominant eptidope
located in residues 141–159 of the VP1 protein . . . of foot-
and-mouth disease were synthesized and used to raise
antibodies in rabbits . . . The R1 peptides led to higher
serum antibody titers that appeared earlier after the start of
immunization and lasted longer than those obtained with the
correspondign L-peptides. . . . Antibodies to the R1 peptides
cross-reacted strongly with L-peptides and virus particles.

(Regenmortel 380, col. 2).
Analysis
We adopt the Examiner’s findings of fact and reasoning regarding the
scope and content of the prior art (Ans. 14–15; FF 22–23) and agree that the
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claims are rendered obvious by Sette and Regenmortel. We address
Appellants’ arguments below.
Appellants contend that “[e]ven if Sette had disclosed that SEQ ID
NO:1 is useful as a vaccine, which it does not, the results of using it or a
reverse D analogue of SEQ ID NO:1 are unexpected: it is shown to inhibit
HCV replication and to do so by inhibiting NS3 oligomerization. Both of
those results are unexpected and entirely unpredictable based on Sette and
Regenmortel” (Br. 12).
We are not persuaded because Regenmortel teaches that “[a]ntibodies
to the R1 peptides cross-reacted strongly with L-peptides and virus
particles” (FF 23). Thus, the result inherently obtained with SEQ ID NO:1
of Sette would have been expected to remain present when modified as
suggested by Regenmortel, because Regenmortel evidences that
modification with the retro-all-D peptides retains immunogenicity for
vaccine compositions (FF 23).
Conclusion of Law
The evidence of record support the Examiner’s conclusion that Sette
and Regenmortel render claim 32 obvious.

SUMMARY
We affirm the rejection of claims 10 and 37 under 35 U.S.C. § 103(a)
as obvious over Sette. Claims 36 and 38 fall with claims 10 and 37. 37
C.F.R. § 41.37(c)(1)(iv).
We affirm the rejection of claims 15 and 35 under 35 U.S.C. § 103(a)
as obvious over Sette, Kim, Beerens, Bishop, and Arai.
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We affirm the rejection of claim 32 under 35 U.S.C. § 103(a) as
obvious over Sette and Regenmortel.
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