Ex Parte Schwager

Patent Trial and Appeal Board

Aug 25, 2016

13140492 (P.T.A.B. Aug. 25, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
13/140,492 06/17/2011
110 7590 08/26/2016
DANN, DORFMAN, HERRELL & SKILLMAN
1601 MARKET STREET
SUITE 2400
PHILADELPHIA, PA 19103-2307
Kathrin Schwager
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
ATTORNEY DOCKET NO. CONFIRMATION NO.
5026-P0479 l USOl/KDR 8091
EXAMINER
HADDAD, MAHER M
ART UNIT PAPER NUMBER
1644
MAILDATE DELIVERY MODE
08/26/2016 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 KATHRIN SCHWAGER 1
Appeal2014-002384
Application 13/140,492
Technology Center 1600
Before ERIC B. GRIMES, MELANIE L. McCOLLUM, and
JACQUELINE T. HARLOW, Administrative Patent Judges.
McCOLLUM, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to an
endometriosis treatment method. The Examiner has rejected the claims as
obvious. We have jurisdiction under 35 U.S.C. § 6(b). We reverse.
STATEMENT OF THE CASE
According to the Specification, "[ e ]ndometriosis is a common medical
condition in women, and is characterized by growth beyond or outside the
uterus of tissue resembling endometrium, which normally lines the uterus"
1 Appellant identifies the real party in interest as Philogen S.P.A. (App.
Br. 1).
Appeal2014-002384
Application 13/140,492
(Spec. 6: 22-24 ). The Specification also states that "ED-A of fibronectin is
indicated as a vascular marker of endometriosis" (id. at 9: 11-12).
The Specification discloses "a specific binding member, e.g. an
antibody molecule, that binds the ... ED-A[] isoform of fibronectin ... for
use in a method of treatment of endometriosis" (id. at 9: 23-26). The
Specification also discloses that "the specific binding member may be
conjugated to a cytokine, such as IL-10" (id. at 17: 23-24).
Claims 15, 17, 89, 92, and 94-96 are on appeal (App. Br. 3). We will
focus on claims 15 and 94, which read as follows:
15. A method of treating endometriosis in a patient, the method
comprising administering to a patient a therapeutically effective amount of a
medicament comprising a specific binding member which binds the ED-A
isoform of fibronectin operably linked to IL-10, wherein said specific
binding member is an anti-EDA antibody comprising:
(i) a VH domain comprising comprising [sic] a framework and a set of
complementarity determining regions HCDRl, HCDR2 and HCDR3,
HCDRl comprises amino acid sequence SEQ ID NO: 42,
HCDR2 comprises amino acid sequence SEQ ID NO: 56,
HCDR3 Comprises amino acid sequence SEQ ID NO: 60; and
(ii) a VL domain comprising a set of complementarity determining
regions LCDRl, LCDR2 and LCDR3 and a framework, wherein
LCDRl has amino acid sequence SEQ ID NO: 102,
LCDR2 has amino acid sequence SEQ ID NO: 114, and
LCDR3 has amino acid sequence SEQ ID NO: 118.
94. The method of claim 15, wherein the binding member is a small
immunoprotein (SIP).
(Id. at 16: Claims Appendix.)
2
Appeal2014-002384
Application 13/140,492
Claims 15, 17, 89, 92, 95, and 96 stand rejected under 35 U.S.C.
§ 103(a) as obvious over Neri2 in view Varma3 and Tagashira4 (Ans. 2).
Claim 94 stands rejected under 35 U.S.C. § 103(a) as obvious over
Neri in view Varma, Tagashira, and Corvinus5 (Ans. 4).
I
The Examiner relies on Neri for teaching:
a method of delivering a molecule to the neovasculature
( angiogenesis) of tumor metastases in a human or animal
comprising administering to the human or animal an antibody
which binds the ED-A isoform of fibronectin, including F8
antibody comprising the claimed CDR sequences, wherein the
antibody is conjugated to detectable label, a radioisotope, and/or
has biocidal or cytotoxic activity, wherein the VH/VL, domain
framework is a human germline framework comprising the
claimed sequences, wherein the antibody is scFv, diabody ... ,
wherein the biocidal or cytotoxic molecule is cytokine.
(Ans. 2.) The Examiner also finds that Neri "teaches that both endometrium
(the proliferative phase and some vessels of the ovaries) and metastatic
neovasculature (angiogenesis) were strongly positively stained with the flag-
tagged parent anti-ED-A antibody (anti-EDA)" and that Neri "evaluated
different anti-ED-A antibodies and shows that F8 has the best dissociation
2 Neri et al., WO 2008/120101 A2, Oct. 9, 2008.
3 Rajesh Varma et al., Endometriosis and the Neoplastic Process, 127
REPRODUCTION 293-304 (2004).
4 Yukiko Tagashira et al., Interleukin-I 0 Attenuates TNF-a-induced
Interleukin-6 Production in Endometriotic Stromal Cells, 91 FERTILITY &
STERILITY 2185-92 (May 2009 (published online Aug. 8, 2008)).
5 Corvinus et al., US 2008/0248038 Al, Oct. 9, 2008.
3
Appeal2014-002384
Application 13/140,492
constant KD~3.l x10-9" (id.). In addition, the Examiner finds that Neri
"differ[ s] from the claimed invention only in the recitation that the target
delivery is endometriosis and F8-IL- l 0 linked antibody in claim 15" (id.).
The Examiner relies on Varma for teaching "that recent studies of
endometriosis suggest endometriosis can be viewed as a neoplastic process"
(id.). In particular, the Examiner finds that Varma teaches "that like uterine
and breast cancer, endometriosis behaves as an estrogen-dependent
neoplasm" and "that significantly, both cancer and endometriosis share some
of the mediators implicated in this 'inflammatory angiogenesis' model" (id.
at 2-3). The Examiner also finds that Varma teaches:
Pre-clinical studies have shown that endostatin effectively
inhibits tumor growth and shrinks existing tumor blood vessels.
Phase 1 clinical cancer trials of endostatin and angiostatin are
ongoing, and preliminary results show minimal toxicities. Anti-
angiogenic strategies for treating endometriosis exist, but are still
at the experimental phase. Soluble truncated receptor (Flt-I) and
an affinity-purified antibody to human VEGF-A, significantly
inhibited the growth of endometrial explants in a mouse in vivo
model of endometriosis by disrupting the vascular supply. Gene
transfection (using a replication-deficient adenovirus vector
AdAngiostatin) of the endogenous angiogenesis inhibitor
angiostatin to the peritoneum of a mouse was successful in
treating a mouse in vivo model of endometriosis.
(Id. at 3.) In addition, the Examiner finds that Varma teaches "that Tissue
invasion and metastasis are similar in endo[ m ]etriosis" and "provides
examples of agents under investigation for endometriosis and cancer using
the cancer hallmark model" (id.).
The Examiner relies on Tagashira for teaching "that IL-10 attenuates
TNF-a-induced IL-6 mRNA expression and protein production by activating
4
Appeal2014-002384
Application 13/140,492
STAT3 in endometriotic cells" and that "the results suggest that IL-10 plays
a significant role in regulating the inflammatory environment in patients
with endometriosis and may also provide a therapeutic modality for
endometriosis" (id.).
(Id.)
The Examiner concludes:
Those of skill in the art would have had reason to
conjugate[] IL-10 taught by Tagashira et al to the anti-EDA
antibody, F8, taught by [Neri] to target deliver the anti-EDA
antibody conjugated to IL-10 to the endometriosis, because,
EDA is marker of both neovascular structures of endometrium
and metastatic neovasculature as taught by [Neri], and thus a
therapeutic target with F8-IL 10 antibody-cytokine conjugate ....
Alternatively, given that endometriosis and tumor
metastases share some of the mediators implicated in
angiogenesis taught by Varma et al, it would have been obvious
to one skilled in the art at the time the invention was made to
target endometriosis for imaging/diagnosing and treatment with
the referenced anti-EDA antibody as taught by [Neri] conjugated
to IL-10 taught by Tagashira et al because IL-10 plays a
significant role in regulating the inflammatory environment in
patients with endometriosis and may also provide a therapeutic
modality for endometriosis.
Those of skill in the art would have had reason to use the
IL-10 of the Tagashira et al reference as a substitute for the
endometriosis treatment taught [Neri] because, like the bioactive
molecules taught in [Neri], IL-10 attenuates TNF-a-induced IL-6
mRNA expression and protein production and hence treat
endometriosis.
5
Appeal2014-002384
Application 13/140,492
Analysis
Neri relates to "a method of treating a tumour metastases in an
individual comprising administering to the individual a therapeutically
effective amount of a medicament comprising a binding member, e.g. an
antibody molecule, which binds the ED-A isoform of fibronectin" (Neri 4:
22-26). In particular, Neri discloses:
[A ]spects of the present invention employ a conjugate or fusion
between a binding member of the invention and a molecule that
exerts a biocidal or cytotoxic effect on target cells in the lesions
and an antibody directed against an extracellular matrix
component which is present in such lesions. For example, the
biocidal or cytotoxic molecule may be interleukin-2 (IL-2),
doxorubicin, interleukin-12 (IL-12), Interferon-y (IFN-y),
Tumour Necrosis Factor a (TNFa) or tissue factor (preferably
truncated). Such conjugates may be used therapeutically, e.g. for
treatment of tumour metastases and/or tumour as referred to
herein.
Tagashira discloses: "IL-10 attenuates TNF-a-induced IL-6 mRNA
expression and protein production by activating STAT3 in endometriotic
cells. Collectively, the results suggest that IL-10 plays a significant role in
regulating the inflammatory environment in patients with endometriosis and
may also provide a therapeutic modality for endometriosis." (Tagashira
2191.) However, we agree with Appellant that the Examiner has not
adequately explained why it would have been obvious to link IL-10 to Neri's
ED-A antibody and use the resulting product to treat endometriosis.
In particular, the Examiner relies on the disclosure in Neri stating:
The most striking discrimination between liver structures and
metastatic neovasculature was observed for the ED-A and ED-B
6
Appeal2014-002384
Application 13/140,492
domains of fibronectin. In both cases, a strong and specific
staining of the metastatic blood vessels was observed, while
normal liver and virtually all normal organs (exception made for
the endometrium in the proliferative phase and some vessels of
the ovaries) scored negative in this immunohistochemical
analysis (Figure 3A).[6J Importantly, ED-A was also found to be
strongly expressed in the neo-vasculature of human lung
metastases and liver metastases (Figure 4).
(Neri 57: 12-21 (emphasis added).) However, we agree with Appellant that
the Examiner does not adequately explain why a teaching that the
endometrium in the proliferative phase is not negative for anti-ED-A
antibody staining suggests that such an antibody would be a good targeting
moiety for endometriosis (App. Br. 5-6; see also Decl.7 iJ 7).
The Examiner also relies on the teachings in Varma (Ans. 2-3, 8, 16-
17, 19, and 23-24). However, we agree with Appellant that the Examiner
does not adequately explain how Varma suggests that Neri's antibody would
be a good target for endometriosis (App. Br. 6-7).
Conclusion
The Examiner has not set forth a prima facie case that Neri, Varma,
and Tagashira suggest the method of claim 15. We therefore reverse the
6 This teaching states that the endometrium in the proliferative phase is an
exception to the general rule that normal organs are negative for anti-ED-A
staining. However, we agree with Appellant that this does not demonstrate
that endometrium in the proliferative phase, much less endometriosis,
provides strongly positive staining (Reply Br. 2-3).
7 Declaration of Professor Petraglia Under 37 C.F .R. § 1.132 dated April 22,
2013.
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Appeal2014-002384
Application 13/140,492
obviousness rejection of claim 15 and of claims 17, 89, 92, 95, and 96,
which depend from (or we are considering to depend from8) claim 15.
II
In rejecting claim 94, which depends from claim 15, the Examiner
relies on the teachings of Neri, Varma, and Tagashira as discussed above
(Ans. 4). The Examiner finds that the "combined reference teachings differ
from the claimed invention only in the recitation that binding member is a
small immunoprotein (SIP) in claim 94" (id.).
The Examiner relies on Corvinus for teaching an Ll9-SIP (id.). The
Examiner concludes that "[t]hose skilled in the art would have been
motivated to use F8 antibody taught by [Neri] in the SIP technology format
taught by [ Corvinus] in [a] method of treating endometriosis because SIP is
the functional equivalent of F8 and scFv, i.e., would target the
endometrium" (id.).
Appellant argues that Corvinus "fails to compensate for the
fundamental deficiencies noted above in the disclosures of [Neri], Varma
and Tagashira" (App. Br. 14). We conclude that the Examiner has not set
forth a prima facie case that Corvinus suggests that Neri's antibody would
8 An Amendment was filed on September 18, 2013, which changes the
dependency of claim 89 from a cancelled claim to claim 15. It is not clear
from the record whether this Amendment has been entered. However, given
that the Examiner has made no comment on the inclusion of this change to
claim 89 in Appellant's Claims Appendix (App. Br. 16), we are assuming,
for the purpose of this appeal, that this change has been entered.
8
Appeal2014-002384
Application 13/140,492
be good for targeting a treatment to endometriosis. We therefore reverse the
obviousness rejection of claim 94.
REVERSED
9