Ex Parte Rennert

Patent Trial and Appeal Board

Jul 26, 2016

12548366 (P.T.A.B. Jul. 26, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
12/548,366 08/26/2009
26168 7590 07/28/2016
FISH & RICHARDSON (BIOGEN)
P.O. BOX 1022
MINNEAPOLIS, MN 55440-1022
FIRST NAMED INVENTOR
Paul D. Rennert
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.
13751-0055002/Al84US 6978
0
EXAMINER
HADDAD, MAHER M
ART UNIT PAPER NUMBER
1644
NOTIFICATION DATE DELIVERY MODE
07/28/2016 ELECTRONIC
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.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
following e-mail address( es):
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PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
ExpartePAULD. RENNERT
Appeal2013-007648
Application 12/548,366
Technology Center 1600
Before ERIC B. GRIMES, CHRISTOPHER G. PAULRAJ, and
TA WEN CHANG, Administrative Patent Judges.
PAULRAJ, Administrative Patent Judge.
DECISION ON APPEAL
rri"1 • • "1 1 "1 ,..,, ,_ T T r"I ~ n "I ,..,, Al • "1 • "1 • • • "1 "1 ims 1s an appear unaer j) u.~.L. s U4 mvo1vmg crnnns to a memoa
of treating graft-versus-host disease (GVHD). The Examiner rejected the
claims for lack of enablement. We have jurisdiction under 3 5 U.S. C. § 6(b ).
We reverse.
STATEMENT OF THE CASE
Background
The invention at issue relates to a method of inhibiting GVHD by
administering an effective amount of a KIM-1 antagonist (Spec. 3:29-30).
1 Appellant identifies the Real Party in Interest as Biogen Idec MA Inc. (see
Appeal Br. 1).
Appeal2013-007648
Application 12/548,366
The Specification notes that "KIM-1 (Kidney Injury Molecule-I) is a type l
cell membrane glycoprotein" with an extracellular portion ( ectodomain) that
"contains a six-cysteine immunoglobulin-like domain and a T/SP rich
domain characteristic of mucin-like 0-glycosylated proteins" (Id. at 1:7-10).
"KIM-1 is a member of a gene family known as the TIM ( T cell
[mmunoglobulin and Mucin domain) family" (Id. at 1: 17-18).
According to the Specification, "[i]t has been discovered that
treatment of a mammal with a KIM-1 antagonist alters the interaction of T
cells with other immune system cells," and furthermore "blockade of the
binding of KIM-1 to its receptor reduces secretion of IFN-y by immune cells
engaged in an antigen response in the mixed lymphocyte response (MLR)
assay" (Id. at 2:2-9). The Specification further discloses that "[m]uch of the
damage in graft-versus-host disease (GVHD) results directly from actions of
donor T cells that become activated in the host (in response to host
antigens), once grafted, e.g., in a bone marrow transplant," and "[b]y virtue
of its ability to interfere with T cell activation, the present invention is useful
for inhibiting GVHD" (Id. at 9: 18-21 ).
The Claim
Claims 42 and 43 are under appeal, and are reproduced in the Claims
Appendix of the Appeal Brief. Independent claim 42 is representative and
reads as follows:
42. A method of treating an immunological disorder in a subject
in need thereof, the method comprising administering to the
subject an effective amount of a composition comprising an
antagonist antibody or antigen-binding fragment thereof that
binds to KIM-1, wherein the immunological disorder is graft-
versus-host disease.
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Appeal2013-007648
Application 12/548,366
(Br. 8).
The Re} ection
The Examiner has rejected claims 42 and 43 under 35 U.S.C. § 112,
first paragraph as lacking enablement (Ans. 3-15).
PRINCIPLES OF LAW
In order for a medical treatment claim to satisfy the enablement
requirement of Section 112, one of ordinary skill in the art must be able to
effectively use the claimed treatment method in order to achieve the desired
therapeutic result. See, e.g., In re '318 Patent Infringement Litig., 583 F.3d
1317, 1325-27 (Fed. Cir. 2009); Rasmusson v. SmithKline Beecham Corp.,
413 F.3d 1318, 1322-25 (Fed. Cir. 2005). When the claims are directed to a
treatment using a particular drug, "[ w ]hat is necessary to satisfy the how-to-
use requirement of§ 112 is the disclosure of some activity coupled with
knowledge as to the use of this activity." In re Cortright, 165 F.3d 1353,
1360 (Fed. Cir. 1999) (citation omitted). The Examiner must set forth a
reasonable basis to question the enablement of the claimed invention. In re
Wright, 999 F.2d 1557, 1562 (Fed. Cir. 1993)
ANALYSIS
The rejection is maintained at least in part based upon the Examiner's
assertion that "[t]he influence of a scientific theory should depend on its
empirical and demonstrable aspects and not its underlying logic" (Ans. 5).
The Examiner finds that "[t]he specification fails to provide empirical data
to show that the claimed method would work in vivo to treat GVHD" (Id.).
In response, Appellant argues that "[t]he inventor of the present application
discovered that treatment of a mammal with a KIM-1 antagonist alters the
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Appeal2013-007648
Application 12/548,366
interaction of T cells with other immune system cells and thereby strongly
suppresses an IgG response to an antigen (see Ex. 5)" and "the working
examples demonstrate that antagonism of KIM-1 reduces secretion of
interferon-gamma by immune cells engaged in an antigen response in the
mixed lymphocyte response assay" and "is therapeutically effective in an in
vivo mouse model of inflammatory bowel disease" (Appeal Br. 2).
On the record before us, we determine that the Examiner has not
established a prima facie case for lack of enablement of the claimed
invention. The Specification includes data showing that administration of an
anti-KIM-I antagonist (i.e., KIM-1-Fc fusion protein) to mice blocks the
production of IgG 1 isotype in response to a challenge with sheep red blood
cells (SRBC), and nearly eliminates IgG production by memory B cells in
response to a subsequent SRBC challenge (Spec. 35-37, Ex. 5; Figs. 3-7).
Further, the Specification discloses an in vitro experiment using a Mixed
Lymphocyte Reaction (MLR) assay, and demonstrates that treatment with an
antagonist anti-KIM-I antibody and KIM-1-Ig fusion protein significantly
reduced the level of IFNy secreted into the supernatant without affecting the
level ofIL-2 or TNF secretion (Spec. 44--46, Ex. 11; Figs. 8-13). Thus,
contrary to the Examiner's assertion, we find that the experimental data
provided in the Specification supports the enablement of the claimed
invention.
We address the Examiner's other reasons for maintaining the
rejection. First, we are unpersuaded by the Examiner's assertion that "while
the specification teaches that KIM-1 is located in T cells, its ligand has not
been identified at the time the invention was made" and "[t]he in vivo effect
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Appeal2013-007648
Application 12/548,366
of any KIM-1 antagonist that inhibits any KIM-1/ligand( s ), as encompassed
by the instant claims, is highly unpredictable ... and can range from
increasing to decreasing T cell responses" (Ans. 5). The claimed method of
treatment does not require the identification of the ligand ofKIM-1. Rather,
claim 42 only requires "administering to the subject an effective amount of a
composition comprising an antagonist antibody or antigen-binding fragment
thereof that binds to KIM-1," and Appellant's Specification makes clear that
the relevant activity to be suppressed or inhibited by the anti-KIM-I
antagonist is the production or secretion of IFNy (Spec. 12, 11. 10-17 ("A
KIM-1 antagonist can be used advantageously to reduce IFNy production in
diseases where IFNy production is excessive or inappropriate.")). The
Specification teaches the use of MLR assays to determine whether an anti-
KIM-1 antagonist reduces the level of IFN y secreted into the supernatant
(Spec 44--46 (Ex. 11) ).
Second, we are also unpersuaded by the Examiner's assertion that
"independent studies of the functions of KIM-1 in CD4 +cn25+ regulatory T
cells provided conflicting results in two transplantation models" (Ans. 6).
The Examiner relies upon references published after the filing date of the
present application to support that assertion. However, "[i]n general, the
examiner should not use post-filing date references to demonstrate that the
patent is non-enabling," with the exception that "a later-dated reference
provides evidence of what one skilled in the art would have known on or
before the effective filing date of the patent application." See MPEP §
2164.05(a) (citing In re Hogan, 559 F.2d 595, 605 (CCPA 1977)). Here, the
Examiner has not shown how the post-filing date references are relevant to
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Application 12/548,366
establishing what the skilled artisan would have known on or before the
priority date of the present application.
Moreover, even if considered, the teachings of the cited references are
not inconsistent with the claimed invention in which an anti-KIM-I
antagonist is used to treat GVHD. For example, the Examiner notes that
"Yuan (Proc Natl Acad Sci USA 2009, 30;106(26):10734-9, of record) teach
that treatment with an antagonist anti-KIM- I mAb (RMTI-10 mAb) aids in
the induction of transplant tolerance via blockage of pro inflammatory
cytokine IL-17 production" (Ans. 6). The "induction of transplant
tolerance" with an anti-KIM-I antagonist would appear to be consistent with
using an anti-KIM-I antagonist to treat GVHD.
The Examiner further notes that "Degauque et al (J. Clin. Invest.
2008; 118(2): 735-741, of record) teach that agonist KIM-I-specific mAbs
(3B3 mAb) serve to prevent allogeneic transplant tolerance" (Ans. 6). The
use of an agonist that promotes KIM-1 activity to "prevent allogenic
transplant tolerance" would also appear to be consistent with using an anti-
KIM-1 antagonist (that suppresses KIM-1 activity) to treat GVHD.
The Examiner also notes that "Barlow (Clinical & Experimental
Allergy, 41, 1012-1021, 2011, of record) "teach that anti-Timl (KIM-1)
antibodies recognizing the same epitope (clones 3B3 and RMTl-10), but
with different avidities for Tim 1, have been reported to elicit opposite
functional effects (see page 1013, 1st col., ,-i l)" (Ans. 6). Barlow, however,
does not address whether the anti-Timl (KIM-1) antibodies were
antagonistic, and thus the relevance of Barlow's teaching to the claimed
invention is unclear. By contrast, Appellants have introduced into the record
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Application 12/548,366
Sonar et al. (2010) J. Clin. lnvest. 120(8):2767-81, which teaches that TIM-
I antagonists can suppress Th2 cell proliferation and cytokine production,
and thereby provide potential therapeutic benefit in immune-mediated
disorders (Appeal Br. 6).
Finally, we are unpersuaded by the Examiner's reliance upon Brok et
al. (J. Immunol., 151(11):6451-6459, 1993, of record) ("Brok") for its
teaching that "IFNy prevents graft-versus-host disease after allogeneic bone
marrow transplantation in mice" (Ans. 6). Brok teaches "the mechanism of
the effect of prolonged IFN-y injections is the suppression of endogenous
IFN-y" (Brok, 6456). This is consistent with the mechanism taught in the
Specification in which anti-KIM-I antibodies suppress endogenous IFN-y
production in order to prevent GVHD.
We therefore reverse the rejection of claims 42 and 43 under
35 U.S.C. § 112, first paragraph as lacking enablement.
REVERSED
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