Ex Parte Stuhler

Patent Trial and Appeal Board

Dec 28, 2018

14371910 (P.T.A.B. Dec. 28, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
14/371,910 07/11/2014
26813 7590 01/02/2019
MUETING, RAASCH & GEBHARDT, P.A.
P.O. BOX 581336
MINNEAPOLIS, MN 55458-1336
UNITED ST A TES OF AMERICA
FIRST NAMED INVENTOR
Gernot Stuhler
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.
258.00290101 2978
EXAMINER
HALVORSON, MARK
ART UNIT PAPER NUMBER
1642
NOTIFICATION DATE DELIVERY MODE
01/02/2019 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):
ptodocketing@mrgs.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte GERNOT STUHLER 1
Appeal2018-000008
Application 14/371,910
Technology Center 1600
Before RICHARD M. LEBOVITZ, JOHN G. NEW, and
JOHN E. SCHNEIDER, Administrative Patent Judges.
NEW, Administrative Patent Judge.
DECISION ON APPEAL
1 Appellant identifies Julius-Maximilians-Universifat Wurzburg as the real
party-in-interest MannKind Corporation. App. Br. 2.
Appeal2018-000008
Application 14/3 71,910
SUMMARY
Appellant files this appeal under 35 U.S.C. § I34(a) from the
Examiner's Final Rejection of claims 1-3, 5, 8, 9, 14, 15, 17, 18, 23, 24, 30,
32, 33, and 46. Specifically, claims 1-3, 5, 8, 14, 15, 17, 18, 23, 24, 30, 32,
33, and 46 stand rejected as unpatentable under 35 U.S.C. § I03(a) as being
obvious over the combination of Christopherson et al. (US 2009/0130106
Al, May 21, 2009) ("Christopherson"), Harris et al. (WO 94/09131, April
28, 1994) ("Harris"), Hofmeister et al. (US 8,076,459 B2, December 13,
2011) ("Hofmeister"), and R. Glockshuber et al., A Comparison of
Strategies to Stabilize Immunoglobulin Fv-Fragments, 29 BIOCHEM. 1362-
67 (1990) ("Glockshuber").
Claims 1-3, 5, 8, 9, 14, 15, 17, 18, 23, 24, 30, 32, 33, and 46 stand
rejected as unpatentable under 35 U.S.C. § I03(a) as being obvious over the
combination of Christopherson, Harris, Hofmeister, Glockshuber, and K.
Masuda et al., Loss or Down-Regulation of HLA Class I Expression at the
Allelic Level in Freshly Isolated Leukemic Blasts, 98 CANCER SCI. 102-108
(2007) ("Masuda").
We have jurisdiction under 35 U.S.C. § 6(b ).
We AFFIRM.
NATURE OF THE CLAIMED INVENTION
Appellant's invention is directed to a set of polypeptides comprising
two polypeptides each of which comprises a targeting moiety binding to an
antigen and a fragment of a functional domain, in which the two
polypeptides are not associated with each other in the absence of a substrate
with an antigen at its surface and in which, upon dimerization of the
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functional domain fragments, the resulting dimer becomes functional.
Abstr.
REPRESENTATIVE CLAIM
Claim 1 is representative of the claims on appeal and recites:
1. A set of polypeptides comprising:
a first polypeptide P 1 comprising
(i) a targeting moiety Tl,
wherein said targeting moiety Tl specifically binds
to an antigen Al, and
(ii) a fragment F 1 of a functional domain F,
wherein neither said fragment F 1 by itself nor said
polypeptide P 1 by itself is functional with respect to the
function of said domain F,
and
a second polypeptide P2 comprising
(i) a targeting moiety T2,
wherein said targeting moiety T2 specifically binds
to an antigen A2, and
(ii) a fragment F2 of said functional domain F,
wherein neither said fragment F2 by itself nor said
polypeptide P2 by itself is functional with respect to the
function of said domain F,
wherein said antigen Al is different from said antigen A2,
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Application 14/3 71,910
wherein said polypeptide P 1 and said polypeptide P2 are
not associated with each other in the absence of a substrate
that has both antigens A 1 and A2 at its surface, and
wherein said polypeptide P 1 and said polypeptide P2 have,
in the absence of said substrate, a dissociation constant KD
of above 10-7 M,
wherein, upon dimerization of said fragment F 1 of said
polypeptide P 1 with said fragment F2 of said polypeptide
P2, the resulting dimer is functional with respect to the
function of said domain F,
wherein said fragment F 1 comprises a VL domain of an
antibody and said fragment F2 comprises a VH domain of
the same antibody; or wherein said fragment F 1 comprises
a VH domain of an antibody and said fragment F2
comprises a VL domain of the same antibody,
and
wherein said targeting moiety T 1 and T2 comprises an
immunoglobulin module, an aptamer, or a natural ligand
of said antigen Al or antigen A2, respectively.
Claims App'x 1. 2
ISSUES AND ANALYSES
We are persuaded by, and expressly adopt, the Examiner's findings,
reasoning, and conclusion that Appellant's claims are primafacie obvious
2 The Claims Appendix of Appellant's Appeal Brief lacks page numbering.
We have therefore assigned page numbers, beginning with page 1 on the
first page of the Appendix.
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over the combined cited prior art. We address the arguments raised by
Appellant below.
Issue 1
Appellant argues the Examiner erred by failing to articulate any
reason why a person of ordinary skill in the art would have been motivated
to make such a combination. App. Br. 8.
Analysis
The Examiner finds that Christopherson teaches demibodies that
comprise a set of at least two antibodies, such as scFvs each specific for a
different antigen on a target cell. Final Act. 5 ( citing Christopherson ,r,r 18-
23 ). The Examiner finds Christopherson teaches that demibodies have
enhanced target specificity, since each demibody in the set is specific for a
particular antigen. Id. The Examiner finds Christopherson teaches that by
selecting cells or virus having an unusual pair of antigens reduces the risk of
non-specific binding. Id.
The Examiner finds that Christopherson further teaches that each
demibody dimerizes together at the cell surface to form an active complex
which directs a demibody-mediated cellular or complement-mediated
cytotoxicity and/or repair function and/or therapeutic activity. Final Act. 5
( citing Christopherson ,r,r 18-23). The Examiner finds that Christopherson
teaches that each antibody is linked to a non-functional portion which
becomes functional when both antibodies bind antigens in close proximity.
Id. The Examiner finds that Christopherson thus teaches that, when in close
proximity, the reporter or therapeutic or cytotoxic molecule portions
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dimerize and a functional molecule capable of providing a signal or inducing
cytotherapy or cytotoxicity is reconstituted. Id.
The Examiner further finds that Christopherson also teaches that the
antigen-binding portion is a recombinant Fab comprising the complete light
chains, or an scFv specific for an antigen on the surface of a cancer cell such
as a CD antigen or a combination of antigens not found on normal cells,
include CD19, CS20, CD33, CD34, and CD45. Final Act. 5 (citing
Christopherson ,r 153, Table 2).
Finally, the Examiner finds that Christopherson teaches that the
demibodies are useful in the targeting of particular cells such as leukemic
cancer cells. Christopherson Abstr.
However, the Examiner finds, Christopherson neither teaches nor
suggests a demibody wherein the non-functional portions comprises VH and
VL immunoglobulin domains. Final Act. 5. The Examiner finds that Harris
discloses an antibody composition formed by a C-terminal fusion of either a
V H or V L antibody domain to one scFv antibody fragment and its
corresponding partner to the second scFv. Id. (citing Harris Fig. 4).
The Examiner also finds that Hofmeister teaches, inter alia, a
cytotoxically active CD3-specific binding antibody comprising a VH domain
comprising SEQ ID NO: 1 that can be used in a bispecific T-cell engager
antibody. Final Act. 5 (citing Hofmeister col. 3, 11. 43-55; col. 9, 11. 27--44).
The Examiner concludes that a person of ordinary skill in the art
would have been motivated to combine Harris's recombinant-specific
binding proteins comprising two scFv antibodies, each with a separate V H
and VL immunoglobulin domain and Hofmeister's cytotoxically active CD3
specific binding antibody to Christopherson' s demi bodies, which comprise a
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set of at least two antibodies, such as scFvs, each specific for a different
antigen on a target cell, because Christopherson teaches that each scFv is
linked to a non-functional portion, which becomes functional when both
antibodies bind antigens in close proximity. Final Act. 6. The Examiner
notes that Christopherson teaches that when the two scFvs are proximate to
each other, the separate VH and VL immunoglobulin domains form a
complete antigen binding domain, that when the demibodies dimerize at the
cell surface to form an active complex, directs cellular-mediated
cytotoxicity. Id. The Examiner further notes that Hofmeister teaches a
cytotoxically-active CD3-specific binding antibody. Id. The Examiner
concludes that, given the structure of the antibody composition in Harris, the
demi body of Christopherson in which each scFv was linked to a non-
functional portion, which becomes functional when both antibodies bind
antigens in close proximity, and Hofmeister's cytotoxically-active CD3
specific binding antibody, it would have been prima facie obvious to
combine Christopherson's demibodies with Harris' recombinant-specific
binding proteins, and Hofmeister's cytotoxically-active CD3 specific
binding antibody to make a more efficient demi body capable of targeting
cancer cells. Id.
Appellant disputes the Examiner's finding that a person of ordinary
skill in the art one of ordinary skill in the art: "would have been motivated
to combine [Harris]' s recombinant specific binding proteins comprising two
scFv antibodies, each with a separate VH and VL immunoglobulin domain,"
with: "Hofmeister's cytotoxically active CD3 specific binding antibody,"
and: "Christopherson's demibodies which comprise a set of at least two
antibodies." App. Br. 8 (quoting Final Act. 6). According to Appellant, the
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Examiner failed to articulate any reason that one of ordinary skill in the art
would have been motivated to make such a combination. Id. Appellant
recognizes that the Examiner asserted that it would have been obvious to
combine the cited documents "to make a demi body each with a separate V H
and VL immunoglobulin domain of a CD3 antibody," but contends that the
Examiner's assertion falls short of articulating a reason that would have
motivated a person having ordinary skill in the art to make such a structure.
Id. (quoting Final Act. 6).
Furthermore, argues Appellant, the Examiner's conclusion that a
person would have been motivated to: "combine Christopherson's
demibodies with [Harris]' s recombinant specific binding proteins and
Hofmeister's cytotoxically active CD3 specific binding antibody to make a
demibody each with a separate V H and V L immunoglobulin domain of a
CD3 antibody" ignores the teachings of Christopherson. App. Br. 9.
Appellant contends that the claimed polypeptides include targeting moieties
Tl and T2 which, upon binding to a substrate having Al and A2 at its
surface, may dimerize and form a functional F domain ( e.g., a functional
variable region of an antibody) with an additional antigen-specific binding
portion. Id. In contrast, Appellant argues, Christopherson teaches a set of
two complementary demi bodies that each include an antigen-binding
portion, an "agent or portion thereof," and a "member of a binding pair." Id.
( citing Christopherson ,r 18). Appellant asserts that, upon the association of
the two members of the binding pair and the portions of the agent, the
demibodies dimerize, forming a structure with two "antigen binding portions
directed to different antigens." Id. ( citing Christopherson ,r 66).
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Appellant asserts that, to the extent the Examiner finds that a person
of ordinary skill would have been motivated to replace the two antigen
binding portions directed to different antigens of Christopherson with
separate VH and VL immunoglobulin domain[s] of an anti-CD3 antibody, as
taught by Harris and Hofmeister, the Examiner failed to identify any reason
to make the claimed set of polypeptides, because the resulting structure
would lack each of the claimed features including, for example, the targeting
moieties Tl and T2. App. Br. 9.
Furthermore, Appellant argues, to the extent the Examiner concludes
that a person of ordinary skill in the art would have been motivated to
replace the members of a binding pair and/or the portions of the agent that
associate to dimerize the demi bodies of Christopherson with separate V H
and VL immunoglobulin domain[s] of an anti-CD3 antibody, Appellant
asserts that the Examiner did not articulate any reason why a person would
have been so motivated. App. Br. 9.
Furthermore, Appellant alleges, the Examiner ignores the teachings of
Christopherson with respect to the "members of the binding pair" ( also
referred to as "binding members" or "binding partners"). App. Br. 9 ( citing,
e.g., Christopherson ,r,r 18, 56, 60, 66). According to Appellant,
Christopherson teaches that the "binding partners" should be "capable of
interacting with each other to form an association or bond," and provides
examples, including "complementary portions of a leucine zipper, a
receptor-ligand (e.g., cytokine and cytokine receptor), actin and an actin-
binding protein, DNA aptamers." Id. at 9--10 (citing Christopherson ,r 122).
Appellant asserts that Christopherson further teaches that: "upon coming
together in two dimensions in close proximity," the members of the binding
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pair should "form an association or bond" and notes that a leucine zipper is a
"preferred embodiment." Id. at 10 (citing Christopherson ,r,r 122-123; 125).
Appellant argues that Christopherson also teaches that it is the interaction to
form a binding pair that in tum permits interaction of the other portions of
the demi body to generate a functional agent. Id. ( citing Christopherson ,r
18).
In addition, Appellant points out that Christopherson teaches an Fe
domain as the most preferred and predominantly described example of an
agent. App. Br. 10 (citing Christopherson ,r,r 21, 61, claims 6, 9; Fig. 19).
Appellant therefore argues that a person having ordinary skill in the art
would have recognized that two incomplete portions (i.e., the CH2/CH3
domains) of such an agent, like the two halves of a leucine zipper, have a
high binding strength with each other. Id. (citing Spec. 13-14 (disclosing a:
"KD in the range of - 1 o-s to 10-11 M" for constant domains and leucine
zippers")). Appellant argues that a person having ordinary skill in the art
would have therefore understood that the overall, cumulative binding
strength of a leucine zipper and an Fe potion, each of which are especially
preferred components of the demi bodies of Christopherson, would be even
higher. Id.
Consequently, Appellant argues, a person of ordinary skill in the art
would have understood, from the teachings of Christopherson, the
importance of a high binding strength between the two complementary
demibodies to permit[ ] interaction of the other portions of the demibody and
to generate a functional agent. App. Br. 10 ( citing Christopherson
,r 18). In contrast to such a high binding strength, as noted by the Examiner,
at the time of the invention, Fv fragments were known to have limited
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stability at low protein concentrations and under physiological conditions.
Id. ( citing Final Act. 7). According to Appellant, the Examiner has provided
no reason why a person of ordinary skill in the art would have ignored the
teachings of Christopherson that these portions of a demi body should have a
high cumulative binding strength. Id. at 10-11.
We are not persuaded by Appellant's arguments. Christopherson
teaches:
The present invention relates generally to a set of synthetic
immunointeractive molecules referred to herein as "demibodies"
which are useful in targeting particular cells in a subject. More
particularly, the present invention provides a set of demibodies
wherein at least two molecules from within the set, each specific
for a different antigen on a target cell, are required to interact
together at the cell surface in order to form an active complex
which directs demibody-mediated cellular or complement
mediated cytotoxicity and/ or reporter function and/ or therapeutic
activity.
Christopherson ,r 2. Christopherson thus expressly teaches, the targeting
moieties Tl and T2 (i.e., at least two molecules from within the set, each
specific for a different antigen on a target cell). Furthermore,
Christopherson teaches that it was well known in the art that:
Modified antibodies of particular interest are single chain
variable fragments (scFv) carrying the variable region sequences
of the light and heavy chains linked together. scFv antibody
fragments are derived from Fragment antigen binding (Fab)
portions of an antibody comprising the V region of a heavy chain
linked by a stretch of synthetic peptide to a V region of a light
chain.
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Id. at ,r 14. Christopherson thus teaches that it was well known in the art that
modified antibodies, comprising segments of VH and VL linked together as a
single-chain variable fragment could be effectively used in immunotherapy.
Christopherson summarizes its invention as embodying:
[S]ets of at least two demibodies wherein each demibody
comprises an antigen-binding portion, an agent or portion thereof
and one or other member of a binding pair. Two demibodies are
designed such that when in close proximity, each member
constituting one of a complementary binding pair, interacts
forming a binding pair. This in tum permits interaction of
portions of the agent to generate a functional agent or interaction
of two agents which agent or agents have properties resulting in
for example, cell death, cell therapy or providing a reporter
signal.
Christopherson ,r 18. Specifically, with respect to the binding portions of the
demibodies that dimerize, Christopherson requires: "a member of a binding
pair capable of interacting with a member on a second demi body, thereby
forming a binding pair of heterodimers but not homodimers" and "two
binding members so that, in close proximity, both members can interact to
form a binding pair between complementary partners." Id. at ,r,r 56, 60.
Harris is directed to:
A specific binding protein having first and second binding
regions, e.g.[,] antibody Fv fragments, which specifically
recognise and bind to target entities, said binding regions being
contained at least in part on respectively first and second
polypeptide chains, said chains additionally incorporating
respectively first and second associating domains, e.g.[,]
antibody VH and VL domains, which are capable of binding to
each other, causing the first and second polypeptide chains to
combine, thereby providing a single protein incorporating the
binding specificities of said first and second binding regions. The
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first and second binding regions may recognize different target
entities, giving a bispecific binding protein.
Harris Abstr. ( emphases added). Specifically, Harris teaches that, with
respect to Figure 4:
A preferred embodiment of this invention is a bispecific
antibody, formed by a C-terminal fusion of either a VH or VL
antibody domain ( component B) to one scFv antibody fragment
( component A) and its corresponding partner ( component D) to
the second scFv ( component C). Such species is illustrated in
Figure 4.
Harris 24. Figure 4 of Harris is reproduced below:
Fig.4.
Figure 4 of Harris depicts an exemplary embodiment of a
bispecific recombinant antibody formation.
Both Christopherson and Harris therefore teach the formation of
molecules comprising two discrete antigen binding portions (i.e., Tl and T2)
that dimerize to form a bispecific antibody. Harris teaches that the
dimerization occurs through the interaction of the V H and V L fragments,
whereas Christopherson requires that the portions of the demibody forming
the dimer be capable of "forming a binding pair ofheterodimers but not
homodimers." See Christoperson ,r 56.
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We agree with the Examiner that a person of ordinary skill in the art
would have found it obvious to substitute the dimerized V H and V L
fragments of Harris for the binding portions of the demi bodies of
Christopherson, because a person of ordinary skill in the art would have
understood that the complementary V H and V L fragments can bind to each
other and are therefore incapable of forming a homodimer, as required by
Christopherson. See KSR Int'! Co. v. Teleflex Inc., 550 U.S. 398,416 (2007)
("The combination of familiar elements according to known methods is
likely to be obvious when it does no more than yield predictable results").
Appellant argues that the preferred embodiments of Christopherson
form stronger dimeric bonds, i.e., using leucine zippers, than those of the V H
and V L fragments taught by Harris, and that, therefore, a person of ordinary
skill in the art would not have been motivated to combine the references ..
See App. Br. 10. However, Appellant adduces no evidence of record in
support of this argument that the dimeric binding methods of Christopherson
are stronger than those of Harris, nor does Appellant demonstrate that the
V w V L bonds taught by Harris do not fall within the claimed range of KDs.
Indeed, and as we will explain further, infra, Appellants' elected species
comprises VH and VL chains bound together (as taught by Hofmeister). We
consequently accord Appellant's argument in this respect little probative
value. See In re De Blauwe, 736 F.2d 699, 705 (Fed. Cir. 1984) (Arguments
and conclusions unsupported by factual evidence carry no evidentiary
weight).
The Examiner relies on Hofmeister as teaching bispecific antibodies
comprising anti-CD3 which may also include antibodies to tumor antigens
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tumor markers which include EpCAM, CDI9, HER-2, HER-2 neu, HER-3,
HER-4, EGFR, PSMA, CEA, MUC-1 (mucin), MUC2, MUC3, MUC4,
MUC5.sub.AC, MUC5.sub.B, MUC7, Lewis-Y, CD20, CD33, CD30,
CD44v6, Wue-1, Plasma Cell Antigen (see WO 01/47953), (membrane-
bound) lgE, Melanoma Chondroitin Sulfate Proteoglycan (MCSP), STEAP,
mesothelin, Prostate Stem Cell Antigen (PSCA), sTn (sialylated Tn antigen),
PAP (fibroblast activation antigen), EGFRvl 11, lg.alpha., lg.beta., MT-
MMPs, Cora antigen, EphA2, L6 and C0-29CDI9, CCR5 and CD20, which
can be used to treat various B cell malignancies. Final Act. 6 ( citing
Hofmeister col. 12-13, 11. 24--10). These antibodies encompass the
antibodies recited in the dependent claims, and we consequently agree with
the Examiner that it would have been obvious to combine these into the
bispecific antibodies taught by Christopherson and Harris to target
specifically B cell malignancies.
Issue 2
Appellant argues that the Examiner erred in concluding that the
dissociation constant is obvious. App. Br. 11.
Analysis
Appellant argues that the Examiner failed to identify any teaching or
suggestion to include Pl and P2 domains having each of the claimed features
including a dissociation constant, KD, of above 10-7 M. App. Br. 11.
According to Appellant, the Examiner finds that the dissociation constant of
polypeptide Pl and polypeptide P2: "is interpreted as the dissociation
constant of the VH:VL regions of the Fl and F2 fragments." Id. (quoting
Final Act. 6). Appellant asserts that such an interpretation is inconsistent
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with the claim language, because polypeptides Pl and P2 each comprise: (i)
a targeting moiety, wherein said targeting moiety specifically binds to an
antigen, and (ii) a fragment F of a functional domain. Appellant argues that,
although P 1 and P2 include V H and V L regions, the Examiner's alleged
conflation of the dissociation constant of P 1 and polypeptide P2 with only a
single component of each is "inappropriate." Id.
Next, Appellant argues, even if equating the dissociation constant of
P 1 and P2 with the dissociation constant of V H: V L fragments was correct,
the Examiner erred in finding that the claimed dissociation constant of
Hofmeister's anti-CD3 VH:VL fragments would be an inherent property of
the VH:VL fragments. App. Br. 12 (citing Final Act. 7). However, Appellant
argues, the Examiner failed to establish a prima facie case of inherency,
because the Examiner did not show that Hofmeister's anti-CD3 VH:VL
fragments necessarily had the claimed dissociation constant (i.e., a KD of
above 10-7 M).
Of the Examiner's reliance upon Glockshuber as teaching a
dissociation constant for V H: V L of an Fv antibody of 1 x 1 o-6, Appellant
contends that neither Glockshuber nor Hofmeister disclose a dissociation
constant for the anti-CD3 VH:VL fragments of Hofmeister. App. Br. 13
(citing Final Act. 7). Furthermore, Appellant argues, Glockshuber teaches
that the "association constants of antibody Fv fragments ... range from 108
to 105 M-1." Id. at 12 (quoting Glockshuber 1366). Therefore, Appellant
argues, none of the prior art references cited by the Examiner support the
finding that Hofmeister's anti-CD3 VH:VL fragments necessarily have the
claimed KD of above 10-7 M. Id.
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The Examiner responds that Appellant's Specification discloses that:
"wherein said polypeptide Pl and said polypeptide P2 have, in the absence
of said substrate, a dissociation constant KD above 10-7," and that this
passage particularly refers to the KD values as relating to the V H and V L
domains of the antibody. Ans. 15 (citing Spec. 15). Therefore, the
Examiner finds, it is reasonable to interpret the limitation reciting: "wherein
said polypeptide P 1 and said polypeptide P2 have, in the absence of said
substrate, a dissociation constant KD above 10-7" as primarily referring to the
KD value as relating to the dissociation of the V H and V L domains of the
antibody. Id. at 15-16.
The Examiner further finds that Glockshuber teaches that the majority
ofVH:VL fragments would have a KD of above 10-7 M. Ans. 16-17. More
importantly, the Examiner finds that Hofmeister's anti-CD3 VH:VL
fragments are identical to the V H: V L fragments elected by Appellant in their
response to the Restructure Requirement (iv) imposed during prosecution on
January 22, 2016. Id. at 17. The Examiner finds that it would be reasonable
to conclude that the anti-CD3 VH:VL fragments elected by Appellant would
have a KD of above 10-7 M, given that claim 32, which recites: "wherein
said immunoglobulin module comprises a V domain selected from the group
consisting of: (i) a V domain of an anti-CD3 antibody comprising a VL
domain comprising SEQ ID NO: 2 and/or a VH domain comprising SEQ ID
NO: 1," and which ultimately depends from claim 1, which requires the
recited KD of above 10-7. Id.
We agree with the Examiner. On September 23, 2015, the Examiner
imposed a restriction requirement on the claims during prosecution.
Appellant responded on January 22, 2016 (the "Response"), electing, inter
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alia, HLA-A2 as the species of Al antigen and CD45 as the A2 antigen, and
the VL domain of an anti-CD3 antibody as fragment FI and the VH domain of
an anti-CD3 antibody as fragment F2. Response 1-2. The Examiner finds,
and Appellant does not dispute, that this species is identical to Hofmeister' s
disclosed anti-CD3 VH:VL fragments. See Ans. 16. We agree with the
Examiner that, because Appellant's claims require that the immunoreactive
dimer have a KD of above 10-7, the identical polypeptide taught by
Hofmeister would necessarily, and thus inherently, possess the same
dissociation properties, including a KD above 10-7.
We consequently conclude that the cited prior art teaches all of the
limitations of the claims on appeal, and we affirm the Examiner's rejection
of the claims over the combined cited prior art.
Issue 3
Appellant argues that Masuda fails to remedy the alleged deficiencies
in the Examiner's primafacie case of obviousness. App. Br. 14. However,
because, for the reasons we have explained, we affirm the Examiner's
rejection of the claims, we similarly affirm the rejection of the claims over
the cited prior art, including Masuda.
DECISION
The Examiner's rejection of claims 1-3, 5, 8, 9, 14, 15, 17, 18, 23, 24,
30, 32, 33, and 46 under 35 U.S.C. § I03(a) is affirmed.
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No time period for taking any subsequent action in connection with
this appeal maybe extended under 37 C.F.R. § 1.136(a)(l). See 37 C.F.R.
§ 1.136(a)(l)(iv) (2010).
AFFIRMED
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