Ex Parte Goldenberg et al

Patent Trial and Appeal Board

Dec 15, 2016

13214767 (P.T.A.B. Dec. 15, 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.
13/214,767 08/22/2011 David M. Goldenberg IMMU-0006US3 1942
37013 7590 12/19/2016
Rossi, Kimms & McDowell LLP
20609 Gordon Park Square
Suite 150
Ashburn, VA 20147
EXAMINER
SCHWADRON, RONALD B
ART UNIT PAPER NUMBER
1644
NOTIFICATION DATE DELIVERY MODE
12/19/2016 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
Ex parte DAVID M. GOLDENBERG and HANS J. HANSEN
Appeal 2014-006809
Application 13/214,767
Technology Center 1600
Before ERIC B. GRIMES, MELANIE L. McCOLLUM, and
JEFFREY N. FREDMAN, Administrative Patent Judges.
FREDMAN, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal1 under 35U.S.C. § 134 involving claims to a method
for treating an autoimmune disease in a subject who has failed methotrexate
therapy. The Examiner rejected the claims as failing to comply with the
written description requirement and as obvious. We have jurisdiction under
35 U.S.C. § 6(b).
We affirm the rejections based on obviousness.
1 Appellants identify the Real Party in Interest as lmmunomedics, Inc. (See
App. Br. 2).
Appeal 2014-006809
Application 13/214,767
Statement of the Case
Background
“[T]his invention is directed to methods for treating autoimmune
disorders by administering antibodies that bind to a B-cell antigen, such as
the CD22, CD20, CD 19, and CD74 or HLA-DR antigen” (Spec. 1,11. 15-
17).
The Claims
Claims 1—6, 11—23, and 25 are on appeal.2 Claim 1 is representative
and reads as follows:
1. A method of treating an autoimmune disease in a subject
comprising administering a human, humanized, chimeric or
murine anti-CD20 antibody which binds human CD20 and an
anti-TNFa antagonist or anti-IL-1 antagonist, wherein said
subject is a subject that has failed therapy with methotrexate.
The Issues
A. The Examiner rejected claims 1, 2, 5, 6, 11—13, 16—20, 22, and 25
under 35U.S.C. § 112, first paragraph as failing to comply with the written
description requirement (Ans. 2-4).
B. The Examiner rejected claims 1—6, 11—22, and 25 under 35 U.S.C.
§ 103(a) as obvious over FDA3 and Feldmann4 (Ans. 5—6).
2 Claim 25 is not included in the Claims Appendix, but there is no indication
that claim 25 was cancelled during prosecution and both the Examiner and
Appellants include claim 25 in the rejections, so we treat claim 25 as
pending and rejected.
3 FDA Approves Enbrel for Rheumatoid Arthritis,
http://www.pslgroup.com/dg/BCODA.htm, dated Nov. 3, 1998 (“FDA”).
4 Feldmann et al., WO 95/09652 Al, published Apr. 13, 1995 (“Feldmann”).
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C. The Examiner rejected claims 1—6, 11—15, 20-22, and 25 under 35
U.S.C. § 103(a) as obvious over FDA and Curd5 (Ans. 6—7).
D. The Examiner rejected claims 16—19 under 35 U.S.C. § 103(a) as
obvious over FDA, Curd, and Feldmann (Ans. 7—8).
E. The Examiner rejected claims 1—6, 11—23, and 25 under 35 U.S.C.
§ 103(a) as obvious over Le,6 Feldmann, and FDA (Ans. 8—10).
F. The Examiner rejected claims 1—6, 11—15, 20-23, and 25 under 35
U.S.C. § 103(a) as obvious over Fe, Curd, and FDA (Ans. 10-11).
A. 35 U.S.C. § 112, first paragraph
The issue with respect to this rejection is: Does the evidence of
record support the Examiner’s conclusion that the phrase “IF-1 antagonist”
lacks descriptive support in the Specification?
Findings of Fact
1. The Specification teaches:
Cytokine agonists and antagonists may also be used in
multimodal therapies according to the present invention. Tumor
necrosis factor alpha (TNFa) and interleukin-1 (IF-1) are
important in mediating inflammation in rheumatoid arthritis.
Accordingly, anti-TNFa reagents, such as Infiximab [sic,
infliximab] and Etanercept (Embrel [sic, Enbrel]), are useful in
multimodal therapy according to the invention, as well as anti-
IE-1 reagents.
(Spec. 17:15-20).
5 Curd et al., US 7,820,161 Bl, issued Oct. 26, 2010 (“Curd”).
6 Fe et al., US 7,192,584 B2, issued Mar. 20, 2007 (“Fe”).
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Application 13/214,767
2. Feldmann teaches “[Representative inflammatory mediators
include agents which block, diminish, inhibit, or interfere with IL-1 activity,
synthesis, or receptor signalling, such as anti-IL-1 antibody, soluble IL-1R,
IL-1 receptor antagonist, or other appropriate peptides and small molecules”
(Feldman 7:18—23).
3. Le teaches that after treatment with anti-TNF antibody “IL-1
production was abolished” (Le 38:65).
4. Marinova-Mutafchieva7 teaches the availability of “hamster
anti—interleukin-ip (anti—IL-1 P) mAh (B122; Genzyme, West Mailing,
UK)” (Marinova-Mutafchieva 639, col. 2).
Principles of Law
“[I]t is the specification itself that must demonstrate possession. And
while the description requirement does not demand any particular form of
disclosure ... or that the specification recite the claimed invention in haec
verba, a description that merely renders the invention obvious does not
satisfy the requirement.” Ariad Pharms., Inc. v. Eli Lilly and Co., 598 F.3d
1336, 1352 (Fed. Cir. 2010)(citations omitted).
Analysis
The Examiner finds:
The term IL-1 antagonist encompasses a potentially vast array
of molecules which can function as antagonists of IL-1 wherein
said molecules are not disclosed in the specification or known
in the prior art (such as small organic molecules, peptide
7 Marinova-Mutafchieva et al., A comparative study into the mechanisms of
action of anti-tumor necrosis factor a, anti-CD4, and combined anti-tumor
necrosis factor a/anti-CD4 treatment in early collagen-induced arthritis, 43
Arthritis & Rheumatism 638-644 (2000).
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Application 13/214,767
mimetics, nonprotein inhibitors, etc.) and wherein the structure
of said molecules is unpredictable. The claims encompass use
of antibodies which bind IL-1, wherein said antibodies can bind
IL-1 from any animal species, whilst human or murine IL-1
were known in the art, IL-1 from other mammalian species
were not apparently known in the art. The identity of IL-1 from
undescribed animal species is unpredictable. Thus, the written
description provided in the specification is not commensurate
with the scope of the claimed inventions.
(Ans. 3).
Appellants contend that “a quick online search reveals an abundance
of commercially available IL-1 antibodies, and first page printouts are of
record. In summary, all of the sequences needed to prepare a chimeric, or
humanized anti-IL-1 monoclonal antibody were published in 1995” (App.
Br. 4).
We find that Appellants have the better position. Claim 1, as
interpreted in light of the Specification, is broadly drawn to encompass
treatment with IL-1 antagonists. The Specification therefore must adequately
describe that genus of compounds.
In this case, while the Specification does not specifically identify any
IL-1 antagonists (FF 1), the prior art of Feldmann relied upon by the
Examiner specifically discloses “[Representative inflammatory mediators”
that are IL-1 antagonists including anti-IL-1 antibodies and soluble IL-1
receptors (FF 2). Le and Marinova-Mutafchieva, relied upon by either
Appellants or the Examiner, teach antibodies that inhibit IL-1 (FF 3 4).
The present case is therefore most closely analogous to Capon. In
Capon, the prior art provided the underlying information regarding the
members of the genus. Capon teaches that the “Board erred in holding that
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Application 13/214,767
the specifications do not meet the written description requirement because
they do not reiterate the structure or formula or chemical name for the
nucleotide sequences of the claimed chimeric genes.” Capon v. Eshhar, 418
F.3d 1349, 1358 (Fed. Cir. 2005).
In the instant case, the prior art teaches several species which fall
within the claimed genus of compounds. Therefore, this situation is unlike
that in Ariad, where the invention was drawn to an NF-kB inhibitor of which
there was only, at best, a single example disclosed. See Ariad
Pharmaceuticals, Inc. v. Eli Lilly and Co., 598 F.3d 1336, 1356 (Fed. Cir.
2010).
The Examiner finds that “[wjhilst human or murine IL-1 were known
in the art, IL-1 from other mammalian species were not apparently known in
the art. The identity of IL-1 from undescribed animal species is
unpredictable” (Ans. 12).
We are not persuaded. In every situation where patent claims
encompass generic administration, the argument could be raised that not
every animal, or perhaps more narrowly mammalian, species has been
specifically analyzed by the patentee. However, “[i]t is not necessary that
every permutation within a generally operable invention be effective in order
for an inventor to obtain a generic claim, provided that the effect is
sufficiently demonstrated to characterize a generic invention.” Capon, 418
F.3d at 1359.
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Conclusion of Law
The evidence of record does not support the Examiner’s conclusion
that the disclosure of the Specification failed to demonstrate possession and
descriptive support for Claim 1.
B. 35 U.S.C. § 103(a) over FDA and Feldmann
The issue with respect to this rejection is: Does the evidence of
record support the Examiner’s conclusion that FDA and Feldmann render
claim 1 obvious?
Findings of Fact
5. FDA teaches “Enbrel acts by binding tumour necrosis factor
(TNF). . . Enbrel competitively inhibits the binding of TNF molecules to the
TNF receptor (TNFR) sites” (FDA 1).
6. FDA teaches that “Enbrel is an entirely new approach to
management of moderate to severe RA. In clinical studies of patients with
moderate to severe RA, Enbrel has been shown to reduce pain and duration
of morning stiffness and improve the number of swollen and tender joints,
enabling patients to better participate in daily activities” (FDA 1).
7. FDA teaches “Enbrel has been shown to provide dramatic
symptomatic relief, even in patients who have not been successfully treated
with current options” (FDA 1).
8. FDA teaches “Enbrel can be used in combination with
methotrexate in patients who do not respond adequately to methotrexate
alone” (FDA 1).
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9. Feldmann teaches that in “one embodiment of the current
invention, anti-CD4 antibody is used in conjunction with anti-TNF
antibody” (Feldmann 8,11. 3-4).
10. Feldmann teaches that “CD4+ T cell inhibiting agents include
. . . antibodies to B cells including CD5+ B cells, such as CD 19, 20”
(Feldmann 6,11. 7-17).
11. Feldmann teaches that “anti-B cell antibodies can be
particularly useful in the current invention” (Feldmann 6,11. 21-22).
12. Feldmann teaches a “method of treating autoimmune or
inflammatory disease in a mammal comprising administering to said
mammal a therapeutically effective amount of a combination of a CD4+ T
cell inhibiting agent and a TNF antagonist” (Feldmann 37,11. 3-7; claim 1).
13. Marina-Mutafchieva teaches that “we have shown that
combined treatment with anti-CD4 and anti-TNFa results in synergistic
reductions in inflammatory processes and Thl activity, and this probably
accounts for the profound therapeutic effect of this form of combination
therapy in CIA [collagen induced arthritis]” (Marina-Mutafchieva 643, col.
2).
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.”
KSRInt’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007). “If a person of
ordinary skill can implement a predictable variation, § 103 likely bars its
patentability.” Mat417.
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Analysis
We adopt the Examiner’s findings of fact and reasoning regarding the
scope and content of the prior art (Ans. 5—6; FF 5—13) and agree that claim 1
is rendered obvious by FDA and Feldmann. We address Appellants’
arguments below.
Appellants contend “[sjince Feldmann el al. proposes to add
methotrexate therapy, this clearly teaches away from a claim directed to a
method of treating patients that have failed methotrexate therapy” (App. Br.
5).
We find the teaching away argument unpersuasive. A teaching away
requires a reference to actually criticize, discredit, or otherwise discourage
the claimed solution. See In re Fulton, 391 F.3d 1195, 1201 (Fed. Cir.
2004). Here, Feldmann never discourages treatment after methotrexate
failure and Feldmann specifically teaches that in “one embodiment of the
current invention, anti-CD4 antibody is used in conjunction with anti-TNF
antibody” (FF 9). Disclosed examples and preferred embodiments do not
constitute a teaching away from a broader disclosure or non-preferred
embodiments. In re Susi, 440 F.2d 442, 446 n.3 (CCPA 1971).
Appellants contend that FDA
does state that Enbrel is indicated for the reduction in signs and
symptoms of moderately to severely active rheumatoid arthritis
in patients who have an inadequate response to one or more
disease-modifying anti-rheumatic drugs (DMARDs), but
suggests that it [“]be used in combination with methotrexate in
those patients who do not respond adequately to methotrexate
alone.” Accordingly, it does not teach use in patients who have
failed methotrexate therapy as presently claimed.
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Application 13/214,767
(App. Br. 5).
We do not find this argument persuasive because FDA specifically
teaches “Enbrel has been shown to provide dramatic symptomatic relief,
even in patients who have not been successfully treated with current
options” (FF 7) and that there are “patients who do not respond adequately
to methotrexate alone” (FF 8). Thus, the ordinary artisan would have
recognized that some patients have failed therapy with methotrexate alone
and would therefore benefit from other therapies such as those taught by
FDA and Feldmann (FF 6, 9—12).
Moreover, claim 1 is open, using the “comprising” transitional
language, and therefore does not exclude further combination therapy with
methotrexate, but rather limits the patient population to those for whom
methotrexate alone is insufficient. This limited patient population is
expressly identified in FDA as suitable for treatment with the anti-TNFa
antagonist Enbrel (FF 7—8), reasonably rendering combination therapy in
such patients obvious.
Appellants cite a variety of references contending that there are
“reservations with the predictability of the mouse CIA model” including
Williams,8 Londei,9 Feldmann 2010,10 van Holten,11 Vierboom,12 and Plater-
8 Williams et al., Anti-tumor necrosis factor ameliorates joint disease in
murine collagen-induced arthritis, 89 Proc. Nat’1 Acad. Sci. 9784—9788
(1992).
9 Londei et al., Persistence of collagen type Il-specific T-cell clones in the
synovial membrane of a patient with rheumatoid arthritis, 86 Proc. Nat’1.
Acad. Sci. 636-640 (1989).
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Zyberk13. Appellants contend that
a skilled artisan would not extend results with an anti-CD4
antibody in the mouse CIA model to B-cell antibodies. The
teaching in Marinova-Mutafchieva would not suggest that a
combination of B-cell antibodies with anti-TNFa would
achieve effects like those purportedly achieved by a
combination of a “T-cell targeted therapy” with anti-TNFa.
(App. Br. 7).
We find the arguments regarding the cited art unpersuasive. Feldman
2010, van Holten, and Vierboom are post filing date art. However,
references that are published “after the filing date of appellant’s application
. . . are not, therefore, evidence of subject matter known to ‘any person
skilled in the art’ as required by 35 U.S.C. § 112, paragraph 1.” In re Gunn,
537 F.2d 1123, 1128 (CCPA 1976). Moreover, none of these three
references specifically addresses the prior art in this case.
Williams provides additional evidence that “anti-TNF-a/p treatment
causes a significant reduction in the clinical and histopathological severity of
10 Feldmann et al., Anti-TNF Therapy, from Rationale to Standard of Care:
What Lessons Has It Taught Us?, 185 J. Immunology 791—794 (2010)
(“Feldmann 2010”).
11 van Holten et al., Treatment with recombinant interferon-f reduces
inflammation and slows cartilage destruction in the collagen-induced
arthritis model of rheumatoid arthritis, 6 Arthritis Research Today R239—
R249 (2004).
12 Vierboom et al., Preclinical models of arthritic disease in non-human
primates, 12 Drug Discovery Today 327—335 (2007).
13 Plater-Zyberk et al., Anti-CD 5 therapy decreases severity of established
disease in collagen type II-induced arthritis in DBA/1 mice, 98 Clinical
Experimental Immunology 442^447 (1994).
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collagen-induced arthritis” (Williams 9784, col. 2). With regard to Londei
and Plater-Zyberk, neither of these references specifically addresses the use
of anti-CD20 antibodies suggested by Feldmann (FF 10), nor do these
references rebut the teaching of Marina-Mutafchieva that “we have shown
that combined treatment with anti-CD4 and anti-TNFa results in synergistic
reductions in inflammatory processes” (FF 13). We recognize that Marina-
Mutafchieva, like Plater-Zyberk, is drawn to a mouse model, but as we
balance all of the evidence with the specific teachings of FDA and
Feldmann, we remain persuaded that the combination of anti-TNFa and
anti-CD20 antibodies suggested by FDA and Feldmann for treatment of
rheumatoid arthritis is obvious (FF 5—13).
We also agree with the Examiner that the “reference to antiCD4
antibody and the mouse model of Feldmann et al. is irrelevant, because the
claims are not drawn to use of antiCD4 antibody. Appellants’ comments
regarding antiCD5 antibody are also equally irrelevant because the claims
are not drawn to the use of antiCD5 antibody” (Ans. 16).
Conclusion of Law
The evidence of record supports the Examiner’s conclusion that FDA
and Feldmann render claim 1 obvious.
C. 35 U.S.C. § 103(a) over FDA and Curd
The issue with respect to this rejection is: Does the evidence of
record support the Examiner’s conclusion that FDA and Curd render claim 1
obvious?
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Findings of Fact
14. Curd teaches a “method of treating an autoimmune disease in a
mammal comprising administering to the mammal a therapeutically
effective amount of an antagonist which binds to a B cell surface marker”
(Curd, col. 2,11. 60-64).
15. Curd teaches that “[ejxamples of autoimmune diseases or
disorders include, but are not limited to . . . rheumatoid arthritis” (Curd, col.
3,11. 50-62).
16. Curd teaches that “[ejxemplary B cell surface markers include
the . . . CD20 . . . leukocyte surface markers” (Curd, col. 3,11. 13—17).
17. Curd teaches that the “preferred antagonist comprises an
antibody” (Curd, col. 4,11. 31—32).
18. Curd teaches that “the patient is optionally further treated with
any one or more agents employed for treating RA such as . . . methotrexate”
(Curd, col. 27,11. 39-A9).
Analysis
We adopt the Examiner’s findings of fact and reasoning regarding the
scope and content of the prior art (Ans. 6—7; FF 5—8, 14—18) and agree that
claim 1 is rendered obvious by FDA and Curd. We address Appellants’
arguments below.
Appellants contend that “[sjince Curd el al. proposes to add
methotrexate therapy, this clearly teaches away from a claim directed to a
method of treating patients that have failed methotrexate therapy” (App. Br.
9).
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Application 13/214,767
We do not find this argument persuasive because FDA specifically
teaches “Enbrel has been shown to provide dramatic symptomatic relief,
even in patients who have not been successfully treated with current
options” (FF 7) and that there are “patients who do not respond adequately
to methotrexate alone” (FF 8). Thus, the ordinary artisan would have
recognized that some patients have failed therapy with methotrexate alone
and would therefore benefit from other therapies such as those taught by
FDA and Curd (FF 6, 14-17).
Moreover, claim 1 is open, using the “comprising” transitional
language, and therefore does not exclude further combination therapy with
methotrexate as optionally suggested by Curd (FF 18), but rather limits the
patient population to those for whom methotrexate alone is insufficient.
This limited patient population is expressly identified in FDA as suitable for
treatment with the anti-TNFa antagonist Enbrel (FF 7—8), reasonably
rendering combination therapy in such patients obvious.
Conclusions of Law
The evidence of record supports the Examiner’s conclusion that FDA
and Curd render claim 1 obvious.
D-F. 35 U.S.C.§ 103(a)
Appellants reiterate the same arguments regarding treating patients
that have failed methotrexate therapy that we found unpersuasive already
over FDA and Feldmann or FDA and Curd. We remain unpersuaded for the
reasons given above.
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SUMMARY
In summary, we reverse the rejection of 1, 2, 5, 6, 11—13, 16—20, 22,
and 25 under 35 U.S.C. § 112, first paragraph as failing to comply with the
written description requirement.
We affirm the rejection of claim 1 under 35 U.S.C. § 103(a) as
obvious over FDA and Feldmann. Claims 2—6, 11—22, and 25 fall with
claim 1.
We affirm the rejection of claim 1 under 35 U.S.C. § 103(a) as
obvious over FDA and Curd. Claims 2—6, 11—15, 20-22, and 25 fall with
claim 1.
We affirm the rejection of claims 16—19 under 35 U.S.C. § 103(a) as
obvious over FDA, Curd, and Feldmann.
We affirm the rejection of claims 1—6, 11—23, and 25 under 35 U.S.C.
§ 103(a) as obvious over Le, Feldmann, and FDA.
We affirm the rejection of claims 1—6, 11—15, 20—23, and 25 under 35
U.S.C. § 103(a) as obvious over Le, Curd, and FDA.
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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