Ex Parte Wong

Patent Trial and Appeal Board

Mar 15, 2016

12350961 (P.T.A.B. Mar. 15, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO.
12/350,961
Albert Wong
28 Ely Street
7590
FILING DATE
0110912009
03/15/2016
West Haven, CT 06516
FIRST NAMED INVENTOR
Albert Wong
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.
Wong 7857
EXAMINER
NGUYEN, QUANG
ART UNIT PAPER NUMBER
1633
MAILDATE DELIVERY MODE
03/15/2016 PAPER
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.
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte ALBERT WONG
Appeal 2013-003651
Application 12/350,961
Technology Center 1600
Before ERIC B. GRIMES, ULRIKE W. JENKS, and
ROBERT A. POLLOCK, Administrative Patent Judges.
PERCURIAM
uECISION ON APPEAL
This is a decision on appeal 1 under 35 U.S.C. § 134 from the
Examiner's rejection of claims 17-21. We have jurisdiction under 35 U.S.C.
§ 6(b ).
We reverse.
STATEMENT OF THE CASE
The Specification discloses that targeted drug delivery is one way of
minimizing "undesirable systemic side effects" (Spec. 2). "[T]he ideal
method for targeted drug delivery would involve the use of vesicles" (id.).
1 Appellant identifies the Real Party in Interest as Albert Wong (App. Br. 2).
Appeal2013-003651
Application 12/350,961
Claim 17, the only independent claim, is representative of the claims
on appeal and reads as follows:
Issue
17. A growth factor sensitive vesicle, comprising:
an external shell which defines a generally spherical closed
body;
said shell bearing at least two growth factor receptors
having functional growth factor binding domains facing outside
said shell,
at least two of said growth factor receptors each having at
least one non-growth factor binding domain covalently cross-
linked to at least one chemical compound,
at least two of said chemical compounds being capable of
associating to form a chemical compound capable of
destabilizing or permeabilizing said shell, permitting the release
of the contents, if any, originally enclosed within said shell.
The Examiner has rejected claims 17-21under35 U.S.C. § 103(a) as
obvious in view of Chien,2 Ueda,3 Ge,4 and Heltovics5 (Ans. 2---6).
The issue presented is: Does the evidence of record support the
Examiner's conclusion that the combination of Chien, Ueda, Ge, and
Heltovics would have made obvious a growth factor sensitive vesicle that
comprises at least two growth factor receptors that are "cross-linked to at
least one chemical compound, [and] at least two of said chemical
compounds being capable of associating to form a chemical compound
2 Chien et al., WO 2006/107786 A2, Oct. 12, 2006.
3 et al., US 2003/0095962 Al, May 22, 2003.
4 Gaoxiang Ge et al., Effect of Membrane Fluidity on Tyrosine Kinase
Activity of Reconstituted Epidermal Growth Factor Receptor, 282
Biochemical and Biophysical Research Communications 511-514 (2001 ).
5 Heltovics et al., US 7,208,465 B2, Apr. 24, 2007.
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Application 12/350,961
capable of destabilizing or permeabilizing said shell" as required by claim
17 (emphasis added)?
Findings of Fact
1. Chien discloses a technology for "generating stably tethered
structures that have multiple functions or binding specificities" (Chien, if 15;
see Fin. Rej. 3). "[S]tably tethered structures are produced as an exclusive
binary complex of any two components, referred herein as A and B, via
specific interactions between two distinct peptide sequences, one termed
dimerization and docking domain (DDD) and the other anchoring
domain (AD)" (id.).
2. Chien states that a complex of a precursor of A (i.e., A) and a
DDD sequence (A/DDD) is referred to as a (Chien, if 16). "As the DDD
sequence in a effects the spontaneous formation of dimer, A is thus
composed of az" (id.). "[T]he dimeric structure contained in az creates a
docking site for binding to the AD [(anchoring domain)] sequence contained
in b [and] results in a ready association of az and b to form a binary complex
composed of azb" (id.).
3. Chien discloses that the two precursors can be "the same (A=
B) or different (Ai- B). When A= B, the resulting azb complex is composed
of a stably tethered assembly of three subunits, referred to hereafter as a3"
(Chien, if 17). "The first and second precursors may be virtually any
molecule or structure, such as antibodies, antibody fragments ... binding
peptides, fragments of binding proteins, [and] known ligands for proteins or
other molecules," among other things (id., Abstract).
4. Chien discloses conjugates composed of "effectors or carriers
linked to a stably tethered structure in either the azb or a3 format ...
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Application 12/350,961
[wherein] the effector may be ... a diagnostic agent, a therapeutic agent,
[or] a chemotherapeutic agent," among other things (Chien, i-f 24).
5. Ueda discloses "a system for controlling the phenotypic
characteristics of cells. A pair of chimeric polypeptides is anchored in the
plasma membrane, each of which has a variable region sequence and an
effector sequence" (Ueda, Abstract; see Fin. Rej. 4). "The polypeptides are
independent in the absence of antigen, but form a stable complex with each
other when antigen is provided. This drives the effector sequences together
in a manner that produces a receptor activation signal, leading to a
phenotypic change" (id.). "Cells bearing chimeric polypeptides can be used
to measure the concentration of antigen or select cells transfected with a
therapeutic gene" (id.). "The chimeric polypeptides can be used as a switch
to tum on and off characteristics such as proliferation, apoptosis,
degranulation, and protein synthesis, or to target cytolytic cells to antigen-
bearing targets" (id.).
6. Ge discloses that EGFR "was functionally reconstituted into
liposome membrane ... More than 80% of the reconstituted EGFR
possessed right-side out orientation with the EGF binding side facing the
medium" (Ge, Abstract; see Fin. Rej. 4-5). "The reconstituted EGFR
tyrosine kinase was well activated by EGF" (id.).
7. Heltovics discloses "a composition for improving release of a
fragrance from a surface. The composition comprises at least one fragrance
oil[] [and] at least one entrapment material ... [which] form[] an entrapment
structure on the surface" (Heltovics, Abstract; see Fin. Rej. 5). "The
composition also comprises at least one destabilizing material ... and/or at
least one release agent" (Heltovics, Abstract) The destabilizing material
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Application 12/350,961
"permits formation of the entrapment structure on the surface but ...
destabilize[ s] the entrapment structure by providing at least one trigger
molecule which preferentially associates with the entrapment material" (id.).
8. Heltovics discloses that entrapment materials include liposomes
(Heltovics, col. 9, 11. 38-39).
9. Heltovics discloses that trigger molecules "act by preferentially
associating with the entrapment material, over the fragrance oil ... [to
cause] displacement of the fragrance oil from the entrapment structure"
(Heltovics, col. 12, 11. 29--42). "In addition ... the formation of hydrogen
bonds between the entrapment material and the trigger molecule(s), also
disrupts hydrogen bonds between adjacent complex molecules, thereby
exposing individual complex molecules and facilitating" fragrance oil
release (id. at col. 12, 11. 42--48).
10. Heltovics discloses that "the trigger molecule is encapsulated .
. . . [which] prevents the contact (and mixing) of the encapsulated trigger
molecules with the rest of the formulation prior to application and
immediately after application to a surface such as the skin" (Heltovics, col.
12, 11. 53-57). "After application, the encapsulated trigger molecules can be
released gradually or in bursts over time by gradual (passive) or activated
(active e.g. rubbing the arm) break down, decomposition or rupture of the
encapsulating material" (id. at col. 12, 11. 57---61 ).
11. Heltovics discloses that "[a]ny known or conventional
incompatible surfactants can be used as trigger molecules in the present
method ... includ[ing] nonionic, anionic, amphoteric and zwitterionic
surfactants and mixtures thereof' (id. at col. 14, 11. 7-13).
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Application 12/350,961
Analysis
Chien discloses the production of bifunctional molecules (FF 1--4).
However, the Examiner finds that Chien does not disclose a growth factor
sensitive liposome or shell comprising growth factor receptors "covalently
linked to at least one chemical compound, at least two of the chemical
compounds being capable of associating to form a chemical compound
capable of destabilizing or permeabilizing said shell" or liposome (Fin. Rej.
3--4 (emphasis removed).)
The Examiner finds that Ge discloses that the epidermal growth factor
receptor (EGFR) "was functionally reconstituted into liposome membrane,
with [the result that] more than 80% of the reconstituted EGFR possessed
right-side-out orientation with the EGF binding side facing the medium and
[the result that] the reconstituted EGFR tyrosine kinase was well activated
by EGF" (Fin. Rej. 4--5 (citing Ge, Abstract) (emphasis removed); see FF 6.)
The Examiner finds that Ueda discloses "a system comprising a pair
of chimeric polypeptides anchored in the plasma membrane. . . . [T]he
polypeptides are independent in the absence of antigen but form a stable
complex with each other when an antigen is provided" (id.). (Fin. Rej. 4
(citing the Abstract and Summary of the Invention) (emphasis removed); see
FF 5.)
The Examiner finds that Heltovics discloses "the use of a destabilizing
material comprising at least one trigger molecule such as ... incompatible
surfactants ... to destabilize an entrapment structure such as a liposome to
release an entrapment agent" (Fin. Rej. 5; see FF 7-11).
The Examiner finds that both Ueda and Heltovics "are related to a
controlled release of an entrapment agent within a cell and a liposome ...
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Application 12/350,961
respectively" (Ans. 7, emphasis removed). The Examiner concludes that it
would have been obvious to one of ordinary skill in the art to modify Chien
by
preparing a liposome compnsmg at least two growth factor
receptors on its outer membrane which form a stable complex
with each other only in the presence of a cancer associated
antigen . . . to produce a receptor activation signal, including
bringing together incompatible surfactant molecules that are
covalently-linked to the effector sequences of the growth factor
receptors to destabilize the liposomal membrane and release the
entrapped agents of diagnostic or therapeutic function, in light of
the teachings of Ueda et al, Ge et al, and Heltovics et al.
(Fin. Rej. 5.). "An ordinary skilled artisan would have been motivated to
carry out the above modifications because the release of entrapped
diagnostic or therapeutic agents in the liposomes would be activated only in
the presence of a cancer associated antigen such as VEGF, placental growth
factor, insulin-like growth factor or EGF" (id., emphasis removed).
Appellant argues that the proposed combination of Chien, Ueda, Ge,
and Heltovics "requires a series of complicated, non-intuitive combinative
steps that are too involved to be considered obvious" (App. Br. 3).
Appellant argues that it would not have been likely for a person of ordinary
skill in the art to apply the disclosure of Heltovics on the "extended release
of a fragrance ... toward the development of a growth factor sensitive
therapeutic vesicle that ... destabilizes and releases its contents up[ on]
exposure to particular external conditions (namely ... growth factors)" (id.
at 4).
We agree with Appellant that the Examiner has not adequately
explained how the combination of the cited references would have made
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Application 12/350,961
obvious the growth factor sensitive vesicle of claim 17. Chien discloses that
a binary complex of two tumor targeting moieties, e.g. two antibody
moieties, may be used to deliver liposomes containing chemotherapeutic
agents to a tumor site (FFs 2 and 3), but Chien does not disclose any specific
mechanism for release of the chemotherapeutic agents from the liposomes.
Although Ueda discloses that a pair of polypeptides that are anchored in the
plasma membrane of a cell may form a stable complex with each other in the
presence of antigen, with the result that activation signal is generated within
the cell which effects a phenotypic change (FF 5), there is no suggestion that
such a system can be applied to liposomes to effect release of liposomal
contents. Ge only discloses that epidermal growth factor receptor activity
may be reconstituted in a liposome (FF 6) Heltovics discloses that a
fragrance may be delivered to a surface of an entrapment structure such as a
liposome in conjunction with a destabilizing material that comprises
encapsulated trigger molecules (FFs 7-11 ).
We find, however, that there is no reasonable expectation of "bringing
together incompatible surfactant molecules [ (trigger molecules)] that are
covalently-linked to the effector sequences of the growth factor receptors to
destabilize the liposomal membrane and release the entrapped agents of
diagnostic or therapeutic function" (Final Act. 5). Heltovics explains that
because "the trigger molecule is capable, of itself, of complexing with the
entrapment material" (i.e. the liposome) it is necessary to encapsulate the
trigger material; "if not encapsulated, [it] would reduce the ability of the
entrapment material to complex with the at least one fragrance oil" or other
payload (Heltovics 13: 34--38; see also FFs 9 and 11).). Here, there is no
suggestion that the use of an encapsulated trigger molecule would result in
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Application 12/350,961
destabilizing or permeabilizing the liposome entrapment material.
Accordingly, we find that the Examiner has not adequately explained how
the cited references, individually or in combination, suggest providing two
chemical compounds, bound to growth factor receptors in the shell of a
vesicle, that are capable of associating to form another chemical compound
that is capable of destabilizing or permeabilizing the vesicle to release
contents from the vesicle.
Thus, we reverse the rejection of independent claim 1 7 and dependent
claims 18-21 as being obvious in view of Chien, Ueda, Ge, and Heltovics.
Conclusion of Law
The Examiner has not adequately established how the combination of
Chien, Ueda, Ge, and Heltovics would have made obvious the growth factor
sensitive vesicle of claim 17 that comprises at least two growth factor
receptors "cross-linked to at least one chemical compound, at least two of
said chemical compounds being capable of associating to form a chemical
compound capable of destabilizing or permeabilizing said shell" (emphasis
added).
SUMMARY
We reverse the rejection of claims 17-21under35 U.S.C. § 103(a).
REVERSED
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