Ex Parte Levin et al

Board of Patent Appeals and Interferences

Sep 21, 2010

11150533 (B.P.A.I. Sep. 21, 2010)

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.
11/150,533 06/10/2005 Steven D. Levin 013952-011500US 3624
84078 7590 09/21/2010
Townsend and Townsend and Crew LLP
Two Embarcadero Center-8th Floor
San Francisco, CA 94111
EXAMINER
JIANG, DONG
ART UNIT PAPER NUMBER
1646
MAIL DATE DELIVERY MODE
09/21/2010 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 STEVEN D. LEVIN, ROLF E. KUESTNER, ZEREN GAO,
STEPHEN R. JASPERS, and JANINE BILSBOROUGH,

Appellants.
_________________

Appeal 2010-004891
Application 11/150,533
Technology Center 1600
_________________

Before SALLY GARDNER LANE, RICHARD TORCZON, and SALLY C.
MEDLEY, Administrative Patent Judges.

LANE, Administrative Patent Judge.
DECISION ON APPEAL1

1 The two-month time period for filing an appeal or commencing a civil
action, as recited in 37 C.F.R. § 1.304, or for filing a request for rehearing,
as recited in 37 C.F.R. § 41.52, begins to run from the “MAIL DATE”
(paper delivery mode) or the “NOTIFICATION DATE” (electronic delivery
mode shown on the PTOL-90A cover letter attached to this decision.
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I. STATEMENT OF THE CASE
The appeal, under 35 U.S.C. § 134, is from a Final Rejection of claims
45-50. Appellants canceled claims 1-44 and 51-61. (Reply Br. 1). We have
jurisdiction under 35 U.S.C. § 6(b). We reverse.
Appellants’ specification is directed to antagonists of certain
proinflammatory cytokines. Proinflammatory cytokines contribute to the
progression of autoimmune and inflammatory diseases. Thus, antagonists
that do not allow a proinflammatory cytokine to bind to its receptor and
carry out its biological activity, may ameliorate such diseases. (Spec. 2, ll.
1-8). The proinflammatory cytokines that are of interest to Appellants’
claims are in the IL-17 family, particularly IL-17A and IL-17F. (App. Br.
18-19; Claims App’x).
The Examiner relied on U.S. Patent Application Publication
2002/0177188, which was published November 28, 2002 (“Chen”), to reject
claims 45-50 under 35 U.S.C. § 103(a). Appellants do not argue for the
separate patentability of any of the claims. (App. Br. 5). Thus, we focus on
independent claim 45 in our review. See 37 C.F.R. § 41.37(c)(1)(vii).
II. FINDINGS OF FACT
1. Appellants’ claim 45 recites:
A method of treating a mammal afflicted with inflammatory
bowel disease (IBD), the method comprising:
administering to the mammal afflicted with IBD an effective
amount of an antagonist of both IL- 17A and IL- 17F, wherein the
antagonist is selected from
(i) an antibody or antibody fragment that binds to a polypeptide
consisting of an amino acid sequence as shown in SEQ ID NO:3,
wherein the antibody or antibody fragment is capable of inhibiting the
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interaction of either IL-17A or IL-17F with a polypeptide having the
amino acid sequence of SEQ ID NO:2; and
(ii) a soluble receptor protein comprising a polypeptide having
the amino acid sequence as set forth in SEQ ID NO:3 or a fragment
thereof that is capable of binding IL- 17A or IL- 17F; wherein the
inflammatory activity of both IL-17A and IL-17F in the mammal is
reduced.

(App. Br. 18; Claims App’x).

2. Appellants’ specification explains that SEQ ID NO: 22 is a
receptor for both IL-17A and IL-17F. (Spec. p. 8, ll. 23-25). Appellants’
specification also explains that SEQ ID NO: 3 is the extracellular ligand-
binding domain of this receptor. (Id. p. 8, l. 31, through p. 9, l. 1).
3. Chen teaches that IL-17A3 may contribute to medical
conditions related to immune function, including inflammatory bowel
disease and that other members of the IL-17 family are of interest. (Chen
¶ [0020)]).
4. Chen provides an amino acid sequence of an IL-17 family
receptor, which we call “the IL-17F receptor,” in SEQ ID NO:14 4. (Chen
¶ [0538] and Fig. 14).
5. The Examiner found, and Appellants do not dispute, that Chen
SEQ ID NO: 14 is 99.6% identical to the amino acid sequence of
Appellants’ SEQ ID NO: 2 and that the amino acids of the extracellular

2 Appellants’ specification refers to SEQ ID NO: 2 as “ZcytoR14.” (Spec. p.
8, ll. 31-32).
3 We use the term “IL-17A” to mean the protein “IL-17” discussed in Chen.
(See Ans. 5; see also Spec. p. 4, l. 13).
4 Also called “PR020040” in Chen. (See Chen ¶ [0063]).
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domain of Chen SEQ ID NO: 14 and the IL-17F receptor (Appellants’ SEQ
ID NO: 3) are 100% identical. (Ans. 3).
6. Chen teaches the soluble extracellular domain of the IL-17F
receptor, which is the same as Appellants’ SEQ ID NO:3. (Ans. 3; Chen
¶ [0075] and claim 10(d), p. 83).
7. Chen teaches that the IL-17F ligand5 binds to both the IL-17A
receptor (“the IL-17A receptor”)6 and the IL-17F receptor. (Chen ¶¶ [0130],
[0653], [0761], and Fig. 35).
8. Chen suggests that when IL-17F binds to a receptor (either the
IL-17A receptor or the IL-17F receptor) it has the same downstream effects
as does IL-17A binding to the IL-17A receptor. (Chen ¶ [0762]; see also
Chen Fig. 35).
9. Chen teaches that IL-17A and IL-17F have similar amino acid
sequences and are both expressed in activated T-cells. Chen reports that
studies on the activities of IL-17F, such as its ability to elevate the
production of G-CSF and IL-8, suggest that it “possesses broad ability to
induce the production of molecules known to be regulated by IL-17[A].”
(Chen ¶ [0745]).

5 Also called PR020110 in Chen.
6 We use the term “IL-17RA” to mean the protein “IL-17R” discussed in
Chen. (See Ans. 9, see also App. Br. 7).
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10. Figure 44 of Chen is reproduced below:

Figure depicts a graph showing the results of Example 31, specifically, the
expression levels of different IL-17 family members in wild type mice, mice
mimicking mild IBD, and mice mimicking severe IBD. IL-17A (“IL-17”)
levels are increased in mice mimicking mild or severe IBD, while IL-17E
levels are decreased in mice mimicking severe IBD, compared to wild type
mice. (Chen ¶ [0726] and Fig. 44).
11. Appellants rely on the Declaration of Katherine Lewis Under
37 C.F.R. § 1.132. (“Lewis Declaration”; see Appeal Br. 9-15).
12. Dr. Lewis is a Senior Scientist, Autoimmunity and
Inflammation, at ZymoGenetics, Inc. the real party-in-interest of the claims
on appeal. (See Lewis Declaration ¶ 2; App. Br. 3). Dr. Lewis received a
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Ph.D. in Nutritional Biochemistry from the University of California, Davis,
and reports that she has over 20 years scientific experience in the fields of
inflammation and animal modeling of disease. (Lewis Declaration ¶ 3).
13. Dr. Lewis states in her Declaration that those of skill in the art
would not have reasonably concluded from the results shown in Figure 44 of
Chen that IL-17F is present during IBD because the level of only one of the
four IL-17 family members tested was elevated or “upregulated,” in IBD.
(Lewis Declaration ¶ 16).
14. Dr. Lewis states in her Declaration that the nature of IL-17F
regulation during IBD is an unknown and unpredictable factor. (Lewis
Declaration ¶ 17).
15. Dr. Lewis states in her Declaration that although Chen reports
that IL-17F induces IL-8, as IL-17A does, other cytokines, such as IL-17E
are also reported to induce IL-8. (Lewis Declaration ¶ 21).
16. Dr. Lewis states that the ability to induce IL-8 is not necessarily
indicative of involvement of or levels of IL-17 family members in IBD, as
evidenced by the increased level of IL-17A and decreased level of IL-17E in
an animal model of the disease, and merely underscores the unpredictability
of their action. (Lewis Declaration ¶ 21 and 22).
17. Dr. Lewis cites Chen for teaching that IL-17E induces
production of IL-8, as does IL-17A, “suggesting the biological activities of
these two cytokines [IL-17A and IL-17E] may be similar.” (Lewis
Declaration ¶ 21; Chen ¶ [0679]).
18. Dr. Lewis states in her Declaration that those of skill in the art
would not have had a reasonable expectation of success in using soluble IL-
17F receptor to treat IBD from Chen because Chen does not provide any
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teaching or suggestion that the IL-17F receptor binds a ligand involved in
IBD, that IL-17F is upregulated in IBD, or that the IL-17F receptor binds IL-
17A. (Lewis Declaration ¶ 25).
III. ISSUE
Would those of skill in the art have had a reasonable expectation of
success in using the soluble extracellular domain of the IL-17F receptor
(encoded by Appellants’ SEQ ID NO: 3 and the extracellular domain of
Chen’s SEQ ID NO: 14) as a way to reduce the inflammatory activity of IL-
17A and IL-17F and treat IBD, from the teaching of Chen?
IV. ANALYSIS
One of the methods of treating a mammal afflicted with IBD recited in
Appellants’ claim 45 entails administering a soluble receptor protein
comprising the polypeptide of SEQ ID NO: 3, which is capable of binding
IL-17A or IL-17F, and of reducing the activity both IL-17A and IL-17F.
(FF7 1, App. Br. 18, Claims App’x).
Chen discloses a family of IL-17 cytokines related to IL-17A that are
of interest in treatments for immune disorders. (FF 2; Chen ¶ [0020]). One
of the cytokines discussed in Chen, IL-17F, binds two receptors: the receptor
known to bind IL-17A (“the IL-17A receptor”) and a newly identified
receptor, which binds IL-17F (“the IL-17F receptor”). (FF 6; Chen
¶¶ [0130], [0653], [0761], and Fig. 35). Chen provides the sequence of the
IL-17F receptor, which has the same extracellular ligand-binding domain as

7 “FF” indicates Finding of Fact.
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Appellants’ SEQ ID NO: 3. (FFs 4-6; Chen SEQ ID NO: 14,
¶ [0538], and Fig. 14; Ans. 3).
Chen suggests that binding of IL-17F to any receptor (including the
IL-17A receptor or the IL-17F receptor) has the same downstream effect as
when IL-17A binds its receptor. (FF 8; Chen ¶ [0762] and Figure 35). Chen
also teaches that IL-17A expression is increased in a mouse model of IBD
(FF 9; Chen ¶ [0726] and Fig. 44).
According to the Examiner, it would have been obvious to administer
a polypeptide of Appellants’ SEQ ID NO:3 to treat IBD because this
polypeptide can block IL-17F binding to any receptor when the soluble
ligand-binding domain of Appellants’ SEQ ID NO: 3 will occupy available
IL-17F. The Examiner relies on the data in Chen that shows IL-17A is
increased in IBD and so, presumably, has a role in IBD that is mediated
through the IL-17A receptor. The Examiner also relies on the suggestion in
Chen that IL-17F has the same effect as IL-17A when bound to a receptor.
(See FF 8). The Examiner reasons that it would, therefore, have been
obvious to block all ligands of the IL-17A receptor, including IL-17F, to
treat IBD. (Ans. 6-7, 8, 9, 10, and 12).
Appellants argue that the Examiner’s logic fails if IL-17F is not
upregulated in IBD and that Chen provides no evidence it is upregulated.
(App. Br. 6). According to Appellants, even if IL-17F is capable of
mediating the same downstream activities as caused by IL-17A activation of
the IL-17A receptor, IL-17F can only do so if it is actually present in a
specific disease state. (App. Br. 9 and 11). Thus, Appellants argue, without
knowing that IL-17F is upregulated in IBD, one would not expect that
blocking its binding to any receptor would have an effect on IBD.
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As evidence, Appellants cite Figure 44 of Chen (FF 10), which shows
that some IL-17 family members are upregulated, but that others, for
example IL-17E, are downregulated. Appellants argue that it is
unpredictable whether targeting IL-17F would have any effect on IBD.
(App. Br. 15-16). Dr. Lewis supports Appellants’ position that those of skill
in the art would not have reasonably concluded from the results of Figure 44
that IL-17F is present in IBD (FF 13; Lewis Declaration ¶ 16). According to
Dr. Lewis, the nature of IL-17F regulation during IBD would have been
unpredictable. (FF 14; Lewis Declaration ¶ 17).
According to the Examiner, Chen specifically teaches a close
relationship between IL-17A and IL-17F, which does not exist among other
IL-17 family members, and presumably makes the upregulation of IL-17A in
IBD, as shown in Figure 44, predictive of the presence of IL-17F in IBD.
(Ans. 13). The Examiner cites to similarities in the sequence, gene
expression, and biological activities of IL-17A and IL-17F. For example,
the Examiner notes that IL-17F stimulates production of the cytokines G-
CSF and IL-8, which are known to also be regulated by IL-17A, that both
IL-17A and IL-17F bind to the IL-17A receptor, and that Chen suggests both
IL-17A and IL-17F have similar downstream activities when they bind the
IL-17A receptor and induce the production of the same molecules (FFs 8
and 9; Chen ¶¶ [0745] and [0762], Chen Fig. 35). (Ans. 13-14).
Appellants argue and provide evidence that the mere induction of
similar molecules would not have indicated to those in the art that because
IL-17A is upregulated in IBD, IL-17F is also upregulated or even present.
Appellants cite to Chen’s discussion of a different IL-17 family member, IL-
17E, which, like IL-17A, induces production of IL-8. (FF 17; Chen
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¶ [[0679]). Like IL-17A and IL-17F, Chen also “suggest[s that] the
biological activities of these two cytokines may be similar.” (Id.).
Appellants’ note, though, that despite the similarity of IL-17A and IL-17E in
some activities, Chen Figure 44 reports that levels of IL-17E is decreased in
severe IBD, while IL-17A is increased. (FF 10; Chen Fig. 44). Appellants
rely on Dr. Lewis to assert that this difference demonstrates how the skilled
artisan would not have reasonably concluded that IL-17F is upregulated in
IBD. (App. Br. 15; FF 16, Lewis Decl. ¶¶ 21 and 22). Dr. Lewis concludes
that those in the art would not have reasonably predicted success in using the
IL-17F receptor or its soluble ligand-binding domain to treat IBD without
knowing whether it binds a ligand involved in IBD. (FF 17; Lewis
Declaration ¶ 25). Dr.Lewis’ testimony is highly material to the issue before
us.
As we have not been directed to evidence to the contrary, we accept
that Chen Figure 44, viewed in light of the statements of Dr. Lewis, shows
that IL-17F activity would not have been predictable to those in the art.
Thus, the Examiner has not provided sufficient evidence that those in the art
would have known from Chen that IL-17F or a ligand that would bind to
Appellants’ SEQ ID NO: 3 would be present in mammals with IBD as a
target for treatment. Without such evidence, we are not persuaded that those
of skill in the art would have had a reasonable expectation of success in
blocking binding of IL-17F to a receptor to treat IBD.

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V. CONCLUSION
We are not persuaded that those of skill in the art would have had a
reasonable expectation of success from Chen to use Appellants’ SEQ ID
NO: 3, which is a soluble extracellular fragment of the IL-17F receptor, as a
treatment for IBD.
The Examiner does not point to any other evidence in Chen that using
an antibody or fragment, as in part (i) of Appellants’ claim 45, would have
rendered the claimed method obvious. (See Ans. 7).
VI. ORDER
Upon consideration of the record and for the reasons given, the
rejection of claims 45-50 under 35 U.S.C. § 103(a) over Chen is
REVERSED.

REVERSED

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