Ex Parte Goldenberg et al

Patent Trial and Appeal Board

Jun 19, 2017

13678832 (P.T.A.B. Jun. 19, 2017)

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.
13/678,832 11/16/2012 David M. GOLDENBERG IMMU-0016US1A 1293
37013 7590 06/21/2017
Rossi, Kimms & McDowell LLP
20609 Gordon Park Square
Suite 150
Ashburn, VA 20147
EXAMINER
ROONEY, NORA MAUREEN
ART UNIT PAPER NUMBER
1644
NOTIFICATION DATE DELIVERY MODE
06/21/2017 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):
mail@rkmllp.com
EOfficeAction@rkmllp.com
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 2016-007109
Application 13/678,8321
Technology Center 1600
Before DONALD E. ADAMS, FRANCISCO C. PRATS,
and DEVON ZASTROW NEWMAN, Administrative Patent Judges.
ADAMS, Administrative Patent Judge.
DECISION ON APPEAL
This appeal under 35 U.S.C. § 134(a) involves claims 1, 3, 5—8, 10,
11, 17, 26, 29, 32, and 37-45 (Final Act.2 2).3 Examiner entered rejections
under 35 U.S.C. § 103(a). We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM and enter a new ground of rejection pursuant to 37
C.F.R. § 41.50(b).
1 Appellants identify the real party in interest as “Immunomedics, Inc.”
(App. Br. 2.)
2 Examiner December 19, 2014 Final Office Action.
3 Pending claims 2, 4, 9, 12—16, 18, 25, 28, 30, and 31 stand withdrawn from
consideration (Final Act. 1). Claims 19-24, 27, and 33—36 are canceled
(Appellants’ August 27, 2014 Response 6, 7, and 9).
Appeal 2016-007109
Application 13/678,832
STATEMENT OF THE CASE
Appellants’ disclosure “relates generally to methods and compositions
for immunotherapy of inflammatory and immune-dysregulatory diseases,
using multispecific antagonists that target at least two different markers”
(Spec. 11). Claim 1 is representative and reproduced below:
1. A multispecific antibody or a combination of separate
antibodies, that reacts specifically with at least two different
targets, wherein said targets are[:]
(A) a cytokine selected from the group consisting of TNF-
a, IL-1, IL-4, IL-5, IL-6, IL-8, IL-12, IL-15, IL-17 and IL-18 or
a chemokine selected from the group consisting of CCL19,
CCL21, IL-8, MCP-1, RANTES, MIP-1A, MIP-1B, ENA-78,
IP-10, GROB, and Eotaxin, wherein said antibody or
combination of separate antibodies acts by neutralizing said (A)
target, and
(B) a proinflammatory effector target which is selected
from the group consisting of MIF, CD74, CD83, C5aR,
LPS/C5a, HMGB-1, TF, TLR2, CD14, VEGF, and TSST-1,
wherein when said multispecific antibody or combination of
separate antibodies comprises a single multispecific antibody,
then CD74 is excluded as a target of said multispecific antibody,
said multispecific antibody or combination of separate
antibodies comprising a therapeutic agent.
(App. Br. 12.)
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Application 13/678,832
The claims stand rejected as follows:
Claims 1, 3, 5—8, 10, 11, 17, 26, 29, 32, and 37-40 stand rejected
under 35 U.S.C. § 103(a) as unpatentable over the combination of Cohen,4
Lu,5 and Hansen6 (Final Act. 3).7
Claims 41—45 stand rejected under 35 U.S.C. § 103(a) as unpatentable
over the combination of Cohen, Lu, Hansen, and Middleton8 (see Final Act.
59).
4 Jonathan Cohen, The immunopathogenesis of sepsis, 420 NATURE 885—
891 (2002).
5 Dan Lu et al., Mechanisms of Signal Transduction: Simultaneous
Blockade of Both the Epidermal Growth Factor Receptor and the Insulin­
like Growth Factor Receptor Signaling Pathways in Cancer Cells with a
Fully Human Recombinant Bispecific Antibody, 279 J. Biol. Chem. 2856—65
(2004).
6Hansen, US 6,458,933 Bl, issued Oct. 1, 2002.
7 Examiner’s Answer included canceled claims 20, 23, and 24 in the
statement of rejection (see Ans. 3; cf Appellants’ August 27, 2014 Response
6 and 9). We did not include canceled claim 20, 23, and 24 in our
deliberations. In addition, Examiner’s Answer failed to list finally rejected
claims 37-40 in the statement of rejection (Ans. 3). We find Examiner’s
failure to list these claims 37-40 in the statement of the rejection, set forth in
the Answer, to represent a typographical error and have included these
claims in our deliberations.
8 Kathryn Middleton et al., Interleukin-6: An angiogenic target in solid
tumours, 89 Critical Reviews in Oncology/Hematology 129—39 (2014).
9 We note that Examiner’s statement of the rejection makes reference to
claims 37-40 (see Final Act. 5). Examiner, however, later makes clear that
the rejection addressed claims 41—45 (id.). Examiner’s Answer also makes
clear that this rejection addresses claims 41—45 (Ans. 6). Therefore, we find
Examiner’s reference to claims 37-40 to represent a typographical error.
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Application 13/678,832
RESTRICTION REQUIREMENT
In response to Examiner’s requirement for a species election,
Appellants elected: “[A] multispecific antibody, IL-6 as the single specific
target A, HMGB-1 as the single specific target B, and angiogenesis inhibitor
as [the] therapeutic agent” (see Appellants’ October 18, 2013 Response 2;
see also App. Br. 6—7). Appellants identified, then pending, claims 1,3,5—
8, 10, 11, 17, 20, 23, 24, 26, 29, and 32 [as] readable on the elected species”
(id. (emphasis added)). At the time of Appellants’ election, original claim
32 depended from Appellants’ claim 27, which depended from Appellants’
claim 1. Appellants’ original claims 1, 27, and 32 are reproduced below:
1. A multispecific antibody or a combination of separate antibodies,
that reacts specifically with at least two different targets, wherein
said targets are (A) a proinflammatory effector of the innate
immune system which is a proinflammatory effector cytokine or
a proinflammatory effector chemokine, wherein said antibody or
combination of separate antibodies acts by neutralizing said (A)
target, and (B) a target specifically associated with an
inflammatory or immune-dysregulatory disorder, wherein said
latter target is not (A) and wherein
(i) when said multispecific antibody or combination of
separate antibodies comprises a single multispecific
antibody, then CD74 is excluded as a target of said
multispecific antibody, and
(ii) when said multispecific antibody or combination of
separate antibodies comprises a combination of separate
antibodies, combinations are excluded where one of said
antibodies targets a B-cell antigen and the other antibody
targets a T-cell, plasma cell, macrophage or inflammatory
cytokine and combinations are also excluded where one of
said antibodies targets CD20 and the other antibody targets
C3b or CD40,
said multispecific antibody or combination of separate
antibodies comprising a therapeutic agent.
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Application 13/678,832
27. A multispecific antibody or combination of separate
antibodies according to claim 1, wherein said proinflammatory
effector target (B) is associated with sepsis or septic shock and is
selected from the group consisting of MIF, CD74, CD83, C5aR,
LPS/C5a, HMGB-1, TF, TLR2, CD14, VEGF, and TSST-1.
32. A multispecific antibody or combination of separate
antibodies according to claim 27, wherein target (A) is selected
from the groups consisting of TNF-a, IL-1, IL-4, IL-5, IL-6, IL-
8, IL-12, IL-15, IL-17 and IL-18, and said therapeutic agent is
activated protein C.
(Appellants’ November 16, 2012 Claims 1, 27, and 32 (emphasis added).)
Therefore, notwithstanding Appellants’ post-Examiner’s Answer
contentions regarding claim 32, Appellants expressly identified claim 32,
which expressly states that the “therapeutic agent is activated protein C,” as
falling within the scope of their elected therapeutic agent: “angiogenesis
inhibitor” (see Reply Br. 3—\\ cf. Appellants’ October 18, 2013 Response 2).
Appellants’ species election and express statement of the claims that read on
the elected species fails to support Appellants’ post-Examiner’s Answer
contention that “Applicant’s [sic] indication of claim 32 as readable on one
of their elected species did not mean that the therapeutic agent recited in the
claim was readable on applicant’s [sic] elected species of angiogenesis
inhibitor” (Reply Br. 3). We are not persuaded and find that Examiner may
rely on Appellants’ express statements and/or admissions on the record (see
Ans. 8 (“from the Examiner’s perspective it could be extrapolated that
‘activated protein C’ was an angiogenesis inhibitor since Appellant [sic]
indicated that claim 32 read on their elected species”)).
In addition, Appellants could have clarified the record at any time
prior to the close of prosecution to make clear that their inclusion of claim
32 as falling within the scope of their elected invention was in error.
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Appellants fail to direct our attention to a portion of this record that provides
such a clarification. Therefore, notwithstanding Appellants’ post-
Examiner’s Answer contentions to the contrary, on this record, we find no
error in Examiner’s reliance on Appellants’ express statement as an
admission that “protein C” falls within the scope of Appellants’ elected
therapeutic agent: “angiogenesis inhibitor” (Appellants’ October 18, 2013
Response 2; cf. Reply Br. 1—2 and 3 4). See RiverwoodInt’l Corp. v. R.A.
Jones & Co., Inc., 324 F.3d 1346, 1354 (Fed. Cir. 2003) (“Valid prior art
may be created by the admissions of the parties”).
Further, notwithstanding Appellants’ contention to the contrary,
Examiner made it explicitly clear that:
Applicant’s election of the species of a multispecific
antibody, IF-6 as the single specific target A, HMGB-1 as the
single specific target B, and angiogenesis inhibitor as therapeutic
agent in the reply filed on 10/18/2013 is acknowledged. Because
applicant did not distinctly and specifically point out the
supposed errors in the restriction requirement, the election has
been treated as an election without traverse (MPEP § 818.03(a)).
Claims 2, 4, 9, 12-16, 18, 25, 28 and 30-31 are withdrawn
from further consideration pursuant to 37 [C.F.R. §] 1.142(b) as
being drawn to a nonelected species, there being no allowable
generic or linking claim. Election was made without traverse in
the reply filed on 10/182013.
Claims 1, 3, 5-8, 10-11, 17, 26, 29, 32 and 37-45 are
currently under consideration as they read on a multispecific
antibody that is specific for IL-6 and HMGB-I and a therapeutic
agent that is an activated protein C or angiogenesis inhibitor.
(Final Act. 2; see also Non-Final Act.10 2 (“Applicant’s [sic] election of the
species of a multispecific antibody, IL-6 as the single specific target A,
10 Examiner’s February 28, 2014 Non-Final Office Action.
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HMGB-1 as the single specific target B, and angiogenesis inhibitor as
therapeutic agent in the reply filed on 10/18/2013 is acknowledged”); see
also Non-Final Act. at 5 (“it would have been obvious to one of ordinary
skill in the art to have further administered activated protein C during the
sepsis therapy because Cohen [] teaches that there is therapeutic potential in
the administration of activated protein C in sepsis []”).) We note with
interest Examiner’s reference to “activated protein C” (id.).
Therefore, we limit our review of Appellants’ claimed invention to the
elected species of: “[A] multispecific antibody, IL-6 as the single specific
target A, HMGB-1 as the single specific target B, and angiogenesis inhibitor
as [the] therapeutic agent,” wherein the angiogenesis inhibitor may be, as
admitted by Appellants, protein C and take no position respecting the
patentability of the non-elected species. See Ex parte Ohsaka, 2 USPQ2d
1460, 1461 (BPAI 1987).
Notwithstanding Appellants’ contention to the contrary, for the
foregoing reasons, we are not persuaded by Appellants’ contention that
Examiner’s “[Rejection of dependent claims to appellant’s [sic] elected
species is antithetical to the election of species requirement in this case, and
they are separately patentable” (App. Br. 6). We address, below, each of
Appellants’ separately argued claims. Claims that are not separately argued
will be grouped with the respective separately argued claim. See In re
Lovin, 652 F.3d 1349, 1357 (Fed. Cir. 2011) (“[T]he Board [has] reasonably
interpreted Rule 41.37 to require more substantive arguments in an appeal
brief than a mere recitation of the claim elements and a naked assertion that
the corresponding elements were not found in the prior art”). Arguments not
made are waived.
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Application 13/678,832
Obviousness:
ISSUE
Does the preponderance of evidence relied upon by Examiner support
a conclusion of obviousness?
FACTUAL FINDINGS (FF)
FF 1. Cohen discloses that “[sjepsis is a condition that results from a
harmful or damaging host response to infection” (Cohen, Abstract; see
generally Ans. 3).
FF 2. Cohen discloses that of the “[mjicrobial components that initiate
[sepsis-related] injury . . . [i]n Gram-negative bacteria, lipopolysaccharide
(LPS: known also as endotoxin) has a dominant role” (Cohen 885; see
generally Ans. 3).
FF 3. Cohen discloses that “mice could be rescued from LPS-induced
shock by administering an antibody to HMGB1” (Cohen 888; see Ans. 3 4).
FF 4. Cohen discloses that “[cjoagulation pathways are initiated by LPS
and other microbial components,” wherein “[p]ro-inflammatory cytokines,
in particular IL-1 and IL-6, are powerful inducers of coagulation” (Cohen
888; see Ans. 4).
FF 5. Cohen discloses that “[i]n septic patients, aPC [(activated Protein C)]
levels are reduced and expression of endothelial thrombomodulin and EPCR
[(endothelial protein C receptor)] are impaired0, providing some support for
the notion that replacement of aPC might have therapeutic value” (Cohen
888; see Ans. 4).
FF 6. Examiner finds that Cohen fails to disclose a multispecific antibody
which targets HMGB-I and IL-6 (Ans. 4).
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FF 7. Examiner relies on Lu to disclose the therapeutic use of bispecific
antibodies, which “retain[] the antigen binding capacity of each of the parent
antibodies and were capable of binding to both targets simultaneously” to
achieve a therapeutically effective result (Ans. 5).
FF 8. Examiner relies on Hansen to disclose “Multivalent molecules which
have at least one specificity for LPS and at least one specificity for the HLA
class II invariant chain are useful in treating sepsis” (Ans. 5).
FF 9. Examiner relies on Middleton to disclose the use of anti-IL-6 as an
anti-angiogenic agent (see Ans. 7; see also Middleton, Abstract).
ANALYSIS
The combination of Cohen, Lu, and Hansen:
Based on the combination of Cohen, Lu, and Hansen, Examiner
concludes that, at the time Appellants’ invention was made, it would have
been prima facie obvious to formulate a bispecific, or multivalent, antibody
comprising anti-HMGB-I and anti-IL-6 with a reasonable expectation of
successfully treating sepsis and, given Cohen’s suggestion of the therapeutic
potential of aPC, to attach aPC to the bispecific, or multivalent, antibody
(see Ans. 5—6).
Claims 1, 38, and 40:
The combination of Cohen, Lu, and Hansen provides a reason,
treatment of sepsis, to combine antibodies that specifically target HMGB-I
and IL-6 into a bispecific, or multispecific, antibody that comprises a
therapeutic agent that is an angiogenesis inhibitor, which, according to
Appellants, may be protein C (FF 1—8; see Appellants’ October 18, 2013
Response 2). Because the cited references provide a reason for combining
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Application 13/678,832
the claimed reagents, we are not persuaded by Appellants’ contention that
the combination of Cohen, Lu, and Hansen fails to make obvious
Appellants’ claimed invention, merely because Cohen discusses prior
clinical trials that make use of other types of reagents and, Lu and Hansen
allegedly fail to make up for Cohen’s asserted deficiency (App. Br. 4—6; see
also id. at 6 (Lu and Hansen “do not overcome the failings of Cohen that are
detailed above”)).
Examiner relies on Lu to disclose the therapeutic use of bispecific
antibodies, which “retain[] the antigen binding capacity of each of the parent
antibodies and were capable of binding to both targets simultaneously” to
achieve a therapeutically effective result (FF 7). Similarly, Examiner relies
on Hanson to disclose the use of multivalent antibodies to treat sepsis (FF 8).
Therefore, we are not persuaded by Appellants’ contentions that: “Fu does
not relate to any of appellant’s [sic] A or B targets, and thus does not
overcome the basic failure of Cohen to suggest a combination as recited in
claim 1” or Hansen’s construct required an “HFA class II molecule,” which
fails to account for the contribution of Cohen to the combination of Cohen,
Fu, and Hansen (see App. Br. 5—6; cf. FF 1—8).
For the foregoing reasons, we are not persuaded by Appellants’
contentions regarding claims 38 and 40 (App. Br. 7—8). In this regard, we
recognize Appellants’ reference to “Remick, et al., Infection and Immunity,
May 2005, vol. 73, p. 2751—2757,” which Appellants’ assert is “appended”
to Appellants’ Brief (App. Br. 8). Upon review of the administrative file, we
are unable to locate a copy of Remick on this record. In addition, we find no
reference to Remick in Examiner’s Answer. Accordingly, we find that
Remick is unavailable for review on this record, not timely filed, and was
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not considered by Examiner. Therefore, we have not included Appellants’
contentions regarding Remick in our deliberations.
Claim 10:
Appellants’ claim 10 depends from and further limits the therapeutic
agent of Appellants’ claim 1 to the group consisting of, inter alia, “an
angiogenesis inhibitor” (App. Br. 12—13). Therefore, we are not persuaded
by Appellants’ contention that “[t]he recitation in claim 10 of an
angiogenesis inhibitor is a presumption that an angiogenesis inhibitor was
not present in claim 1” (App. Br. 10). Notwithstanding Appellants’
contention to the contrary, Appellants’ claim 10 simply limits the scope of
the genus of “therapeutic agent,” set forth in Appellants’ claim 1, to a group
that consists of, inter alia, “an angiogenesis inhibitor” (see App. Br. 12—13).
Further, for the reasons set forth above, the combination of Cohen,
Lu, and Hansen makes obvious a bispecific, or multispecific, antibody
that specifically targets both HMGB-I and IL-6 and further comprises a
therapeutic agent that is an angiogenesis inhibitor, which, according to
Appellants, may be protein C (FF 1—8; see Appellants’ October 18, 2013
Response 2; cf. App. Br. 10-11).
Claim 37:
Claims 37-40 stand rejected over the combination of Cohen, Fu, and
Hansen (see Final Act. 3). Therefore, we have not considered Appellants’
contentions regarding the rejection of claims 37-40 over the combination of
Cohen, Fu, Hansen, and Middleton (see App. Br. 8—10).
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The combination of Cohen, Lu, Hansen, and Middleton:
Each of claims 41—45 depends directly or ultimately from claim 1,
discussed above, and requires at least three components: (1) an antibody
that specifically targets a cytokine that is IL-6, (2) an antibody that
specifically targets a proinflammatory effector target that is HMGB-1, and
(3) a therapeutic agent that is an angiogenesis inhibitor, which, according to
Appellants, maybe protein C (App. Br. 12—14; Appellants’ October 18,
2013 Response 2). As discussed above, Examiner established that the
combination of Cohen, Lu, and Hansen suggests a bispecific, or multivalent,
antibody comprising two of these components: anti-HMGB-1 and anti-IL-6.
Examiner contends that, as evidenced by Middleton, the anti-IL-6 antibody,
satisfies both the: (1) antibody that specifically targets IL-6 and (3)
angiogenesis inhibitor components of Appellants’ claimed invention (see
Final Act. 6). We are not persuaded by that rationale because Examiner
failed to explain in the second rejection why the combination of Cohen, Lu,
Hansen, and Middleton suggests a bispecific, or multispecific, antibody that
comprises three specific components (see Ans. 6—7), as claims 41—45
require.
However, for the reasons discussed above, we find that Cohen
expressly provides a reason to combine (1) an antibody that specifically
targets a cytokine that is IL-6 and (2) an antibody that specifically targets a
proinflammatory effector target that is HMGB-1 into a bispecific, or
multispecific, antibody that comprises (3) a therapeutic agent that is an
angiogenesis inhibitor, which, according to Appellants, may be protein C.
For the foregoing reasons, we are not persuaded by Appellants’
contention that “Middleton’s teaching as to a characteristic of IL-6 does not
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overcome Cohen’s failing in teaching a combination with IL-6 in the first
instance” (App. Br. 11).
CONCLUSION OF LAW
The preponderance of evidence relied upon by Examiner supports a
conclusion of obviousness.
The rejection of claims 1, 10, 37, 38, and 40 under 35 U.S.C. § 103(a)
as unpatentable over the combination of Cohen, Lu, and Hansen is affirmed.
Claims 3, 5—8, 11, 17, 26, 29, 32, 38, and 39 are not separately argued and
fall with claims 1, 10, and 37 respectively.
The rejection of claim 41 under 35 U.S.C. § 103(a) as unpatentable
over the combination of Cohen, Lu, and Middleton is affirmed. Claims 42—
45 are not separately argued and fall with claim 41. Because our rationale
differs from Examiner’s, we designate our affirmance as a new ground of
rejection.
TIME PERIOD FOR RESPONSE
Regarding the affirmed rejection(s), 37 C.F.R. § 41.52(a)(1) provides
“Appellants] may file a single request for rehearing within two months from
the date of the original decision of the Board.”
In addition to affirming the Examiner’s rejection(s) of one or more
claims, this decision contains a new ground of rejection pursuant to 37
C.F.R. § 41.50(b). 37 C.F.R. § 41.50(b) provides “[a] new ground of
rejection pursuant to this paragraph shall not be considered final for judicial
review.”
37 C.F.R. § 41.50(b) also provides that the Appellants, WITHIN
TWO MONTHS FROM THE DATE OF THE DECISION, must exercise
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one of the following two options with respect to the new ground of rejection
to avoid termination of the appeal as to the rejected claims:
(1) Reopen prosecution. Submit an appropriate
amendment of the claims so rejected or new Evidence relating to
the claims so rejected, or both, and have the matter reconsidered
by the examiner, in which event the prosecution will be
remanded to the examiner....
(2) Request rehearing. Request that the proceeding be
reheard under § 41.52 by the Board upon the same record....
Should the Appellants elect to prosecute further before the Examiner
pursuant to 37 C.F.R. § 41.50(b)(1), in order to preserve the right to seek
review under 35 U.S.C. §§ 141 or 145 with respect to the affirmed rejection,
the effective date of the affirmance is deferred until conclusion of the
prosecution before the Examiner unless, as a mere incident to the limited
prosecution, the affirmed rejection is overcome.
If the Appellants elect prosecution before the Examiner and this does
not result in allowance of the application, abandonment or a second appeal,
this case should be returned to the Patent Trial and Appeal Board for final
action on the affirmed rejection, including any timely request for rehearing
thereof.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(1). See 37 C.F.R.
§ 1.136(a)(l)(iv).
AFFIRMED: 37 C.F.R, $ 41.50(b)
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