Ex Parte Rother et al

Patent Trial and Appeal Board

Feb 21, 2017

11596382 (P.T.A.B. Feb. 21, 2017)

United States Patent and Trademark Office
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
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APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
11/596,382 07/16/2008 Russell P. Rother AXJ-117AUSRCE 8996
133485 7590 02/23/2017
Nelson Mullins Riley & Scarborough LLP/Alexion
One Post Office Square
30 th Floor
Boston, MA 02109-2127
EXAMINER
HUYNH, PHUONG N
ART UNIT PAPER NUMBER
1644
NOTIFICATION DATE DELIVERY MODE
02/23/2017 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):
ipboston.docketing@nelsonmullins.com
chris. schlauch @nelsonmullins.com
ipqualityassuranceboston@nelsonmullins.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte RUSSELL P. ROTHER, HAO WANG, and AILI LAO1
Appeal 2016-001058
Application 11/596,382
Technology Center 1600
Before RICHARD J. SMITH, TAWEN CHANG, and
JOHN E. SCHNEIDER, Administrative Patent Judges.
SMITH, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35U.S.C. § 134 involving claims to a method
to prolong survival of an allograft in a recipient human. We have
jurisdiction under 35 U.S.C. § 6(b).
We affirm.
1 According to Appellants, the real party in interest is Alexion
Pharmaceuticals, Inc. (Br. 2.)
Appeal 2016-001058
Application 11/596,382
STATEMENT OF THE CASE
Claims on Appeal
Claims 1, 132, 134, 135, 137, 138, 140-144, 146-152, 155-160, and
162—178 are on appeal. (Appendix A, Br. 15—20.) Claim 1 is illustrative
and reads as follows:
1. A method to prolong survival of an allograft in a recipient human,
said method comprising administering to said recipient human:
(a) an antibody that (i) binds to human complement component C5
and (ii) inhibits cleavage of human complement component C5 into
fragments C5a and C5b; and
(b) at least one immunosuppressive drug,
wherein said antibody is administered chronically to said
recipient human.
Examiner’s Rejection
Claims 1, 132, 134, 135, 137, 138, 140-144, 146-152, 155-160, and
162—178 stand rejected under pre-AIA 35 U.S.C. § 103(a) as unpatentable
over US 7,923,010 B2 (Christadoss et al., issued April 12, 2011
(“Christadoss”)), US 6,428,985 B1 (Bromberg et al., issued Aug. 6, 2002
(“Bromberg”)), and US 6,534,058 B2 (Fung et al. issued Mar. 18, 2003
(“Fung”)), as evidenced by US 5,679,345 (Sanfilippo et al., issued Oct. 21,
1997 (“Sanfilippo”)) and Wang.2 (Final Act. 3—14.)3
The claims are not separately argued, and we therefore limit our
consideration to claim 1.
2 Wang et al., Complement Inhibition with an Anti-C5 Monoclonal Antibody
Prevents Hyperacute Rejection in a Xenograft Heart Transplantation Model,
68 Transplantation 11, 1643-51 (1999) (“Wang”).
3 Office Action dated Oct. 10, 2014. The rejection refers to claim 179, but
claim 179 was cancelled. (Amendment After Final Action, Aug. 4, 2011.)
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Application 11/596,382
FINDINGS OF FACT
We adopt as our own the Examiner’s findings regarding the scope and
content of the prior art, and reasons to combine the cited references. The
following findings are included for emphasis and reference purposes.
FF 1. The Specification states that
A preferred method of inhibiting complement activity is to
use a monoclonal antibody which binds to complement C5 and
prevents C5 from being cleaved. This prevents the formation of
both C5a and C5b-9 while at the same time allowing the
formation of C3a and C3b which are beneficial to the recipient.
Such antibodies that are specific to human complement are
known . . . [and] include both a whole or full-length antibody
(now named eculizumab)
(Spec. 18,11.7-12.)
FF 2. Appellants’ claim 155 states that the antibody of claim 1 “is
eculizumab or an antigen-binding fragment thereof.” (Br. 17.)
FF 3. The Examiner finds that Christadoss teaches a method of
suppressing hyperacute graft rejection of an organ in a human by
administering an antibody such as Eculizumab, “which is a humanized
antibody that binds to human complement component C5 that inhibits the
cleavage of complement component C5 into fragments such as C5a and
C5b.” (Ans. 3, citing Christadoss Abstract, Summary, col. 1,11. 55—58, col.
3,11. 22-25, 60-67, and col. 8,11. 1-8.)
FF 4. Christadoss states that, in addition to the antibodies and other
compounds in the formulations, “active materials that are conventionally
employed to suppress” types of graft rejection other than hyperacute graft
rejection can be included. (Christadoss col. 8,11. 2—8.)
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FF 5. Christadoss states that “[administration can be carried out
continuously or periodically.” (Christadoss col. 8,11. 18—19.) The Examiner
finds this to mean “chronically.” (Ans. 11.)
FF 6. The Examiner finds that Bromberg teaches a method of
suppressing allograft rejection in a human “by administering at least one
conventional immunosuppressive agent,” and that Bromberg teaches “long­
term maintenance immunosuppression (chronic administration).” (Ans. 3—4,
citing Bromberg col. 9,11. 3—13, col. 10,11. 14—18, 27—37, 47, and col. 36,11.
1—55.) See also Example VII teaching allograft survival. (Bromberg col.
42,1. 55-col. 43,1. 15.)
FF 7. The Examiner finds that Fung teaches various anti-C5
monoclonal antibodies, “useful for inhibiting complement activation in vivo,
inflammation and graft rejection,” and studies regarding expression of
human E-selectin in cardiac and renal allografts. (Ans. 4, citing Fung
Abstract, col. 2,1. 64—col. 3,1. 20, col. 5,1. 17, col. 7,1. 14, col. 8,1. 45, and
claims.)
FF 8. Fung teaches that “these studies provide evidence that cytokine-
induced expression of E-selectin by donor organ endothelium contributes to
the binding and subsequent transmigration of inflammatory cells into the
graft tissue and thereby plays an important role in acute cellular allograft
rejection.” (Fung col. 3,11. 12—16.)
FF 9. The Examiner finds that Sanfilippo teaches “that complement is
involved in rejection of transplanted organ grafts,” and that anti-C5
antibodies are “useful for treatment of pathologic activation of complement
system, including allograft rejection.” (Ans. 4—6, citing Sanfilippo cols. 1—
2, col. 25,11. 1^1, col. 37,11. 21-28.)
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FF 10. The Examiner finds that Wang teaches “a method of
prolong[ing] survival of xenograft by administering anti-C5 monoclonal
antibody in combination with at least immunosuppressive agents.” (Ans. 6,
citing Wang Abstract, entire document.)
FF 11. The Examiner finds that Thomas4 is evidence that “a person of
ordinary skill [in] the art has good reason to pursue the known options [] to
inhibit complement C5 activation in the pathogenesis of several chronic
human diseases including allograft rejection using humanized anti-C5
antibody.” (Final Act. 13, citing Thomas 1399, rt. col.)
DISCUSSION
We agree with and adopt the Examiner’s findings, analysis, and
conclusions, as set forth in the Final Action (Final Act. 2—14) and
Examiner’s Answer (Ans. 2—23). We discern no error in the Examiner’s
rejection of the claims on appeal as obvious.
Issue
Whether a preponderance of evidence of record supports the
Examiner’s rejection for obviousness under 35 U.S.C. § 103(a).
Analysis
Appellants advance several arguments in response to the Examiner’s
rejection. (Br. 7—13.) Appellants generally argue the references separately,
and that specific references do not teach particular features of claim 1. (Id. )
However, Appellants are reminded that the test for obviousness is what the
combined teachings of the references would have suggested to one of
4 Thomas et al., Inhibition of Complement Activity by Humanized Anti-C5
Antibody and Single-Chain Fv., 33 Molecular Immunology 17/18, 1389—
1401 (1996) (“Thomas”).
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ordinary skill in the art, In re Keller, 642 F.2d 413, 425 (CCPA 1981) (citing
cases), and that one cannot show nonobviousness by attacking references
individually where the Examiner bases the rejection on a combination of
references, In re Merck & Co., 800 F.2d 1091, 1097 (Fed. Cir. 1986) (citing
Keller, 642 F.2d at 425).
Christadoss
Appellants argue that Christadoss does not teach or suggest the use of
anti-C5 antibodies (particularly Eculizumab) in suppressing graft rejection.
(Br. 8—9, 11.) In particular, Appellants contend that Christadoss cautions
against the use of Eculizumab because of its statement that use of
Eculizumab “must be carefully monitored” due to the possibility of “making
patients more susceptible to bacterial and viral infection.” (Id. at 8, citing
Christadoss col. 1,11. 50—64.) Furthermore, according to Appellants, “the
deficiencies taught by [Christadoss] associated with administering an anti-
C5 antibody having the claimed features (e.g., Eculizumab) would have
motivated the skilled artisan to have looked for targets other than C5 to treat
autoimmune diseases and suppress hyperacute graft rejection.” (Id. at 11.)
Appellants also argue that Christadoss “does not teach or suggest chronic
administration of an anti-C5 antibody to prolong allograft survival.” (Id. at
8.)
We are not persuaded. As an initial matter, a reference (e.g.,
Christadoss) may be read for all that it teaches, including uses beyond its
primary purpose. See In reMouttet, 686 F.3d 1322, 1331 (Fed. Cir. 2012).
Moreover, even if we assume that Christadoss describes Eculizumab as
somewhat inferior to other disclosed antibodies, such a description would
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Application 11/596,382
not constitute a teaching away from Eculizumab. See In re Gurley, 27 F.3d
551, 553 (Fed. Cir. 1994).
Here, as found by the Examiner, Appellants’ anti-C5 antibody
encompasses the antibody described in Christadoss, and thus would have the
same alleged deficiencies as argued by Appellants. (Ans. 9; FF 1, 2.)
Moreover, the Examiner explains in detail reasons why a person of ordinary
skill in the art would have been motivated to use anti-C5 antibody to treat
human patients with allograft and otherwise suppress graft rejection. (Ans.
9—11.) For example, the Examiner explains that “[o]ne of skill in the art
would have been motivated to use eculizumab ... to treat [a] human patient
with allograft because such antibody is expected to reduce immunogenicity
and thus avoid human anti-mouse antibody (HAMA) response” as taught by
Fung.5 (Id. at 9, citing Fung col. 8,11. 61—65.) The Examiner also points to
the teaching in Christadoss regarding “chronically” administering the
antibody. (Id. at 10—11, 16; FF 5.)
Xenograft vs. Allograft Rejection
Appellants argue that Fung and Wang teach prevention of xenograft
rejection (i.e., a graft transplanted between individuals of different species),
and that the teachings of Fung, Wang, and Christadoss do not apply to
allograft rejection (i.e., a graft transplanted between two genetically different
individuals of the same species). (Br. 9—12.) Furthermore, according to
5 Because we agree with the Examiner that one of skill in the art would have
been motivated to use anti-C5 antibody, and particularly eculizumab, we are
not persuaded by Appellants’ argument regarding a lack of such motivation
based on the “deficiencies” of Christadoss and the contention that
Christadoss is the most recent of the cited references “and thus would have
reflected the most recent state of the art.” (Br. 11.)
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Appellants, “the use of xenotransplantation as a model for
allotransplantation is very limited” and “methods for prolonging xenograft
survival would not necessarily be efficacious for prolonging other types of
grafts, such as allografts.” {Id. at 10.) Appellants also take issue with the
Examiner’s reference to Sanfilippo and its teaching that complement is also
involved in allograft rejection.6 {Id. at 11—12.)
We are not persuaded. As the Examiner explains, the teachings of
Fung include that “cytokine-induced expression of E-selectin by donor organ
endothelium . . . plays an important role in acute cellular allograft rejection.”
(Ans. 11—12, 16—17, citing Fung col. 3,11. 11—16; FF 7—8.) The Examiner
also explains in detail Sanfilippo’s teachings of complement activation in
xenograft and allograft rejection. (Ans. 13—14, 17—18; FF 9.) In fact,
Appellants acknowledge that Sanfilippo teaches “the general involvement of
the complement pathway in organ and tissue xenograft and allograft
rejection.” (Br. 12.) Thus, Appellants’distinction between xenograft and
allograft rejection, in connection with any of the cited references, is
unpersuasive.
Reasonable Expectation of Success
Appellants argue that there would not “have been a reasonable
expectation of success that administering to an organ graft recipient an
antibody which binds human complement component C5, in combination
with one or more conventional immunosuppressive drugs, would prolong
allograft survival [in] the recipient.” (Br. 12—13.)
6 A similar argument is made with respect to the teachings of Thomas, and is
similarly unpersuasive for the reasons of record. {See Ans. 22—23.)
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We are not persuaded. All of the features of claim 1 are taught by
Christadoss, in combination with Fung’s teachings and Bromberg’s
teachings, as further supplemented by the other references cited by the
Examiner. (See, e.g., FF 3—11.) Appellants are also reminded that the
reasonable expectation of success requirement “refers to the likelihood of
success in combining references to meet the limitations of the claimed
invention.” Intelligent Bio-Systems, Inc. v. Illumina Cambridge Ltd., 821
F.3d 1359, 1367 (Fed. Cir. 2016). Thus, for example, even if we assume
that the preamble statement of a method to “prolong survival of an allograft”
is a limitation, that feature of claim 1 is taught at least by Bromberg. (FF 6.)
Furthermore, Christadoss, Bromberg, and Wang all teach and suggest
administration of a combination of agents, including an immunosuppressive
agent as claimed. (FF 4, 6, and 10.)
Conclusion of Law
A preponderance of evidence of record supports the Examiner’s
rejection of claim 1 under 35 U.S.C. § 103(a). Claims 132, 134, 135, 137,
138, 140—144, 146—152, 155—160, and 162—178 were not argued separately
and fall with claim 1.
SUMMARY
We affirm the rejection of all claims on appeal.
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
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