Ex Parte Alexis et al

Patent Trial and Appeal Board

Jan 18, 2018

12098354 (P.T.A.B. Jan. 18, 2018)

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.
12/098,354 04/04/2008 Frank Alexis MIT 12388 2137
23579 7590
Pabst Patent Group LLP
1545 PEACHTREE STREET NE
SUITE 320
ATLANTA, GA 30309
EXAMINER
CRAIGO, WILLIAM A
ART UNIT PAPER NUMBER
1615
MAIL DATE DELIVERY MODE
01/18/2018 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 FRANK ALEXIS, LIANGFANG ZHANG,
ALEKSANDAR F. RADOVIC-MORENO, FRANK X. GU,
PAMELA BASTO, ETGAR LEVY-NISSENBAUM, JULIANA CHAN,
ROBERT S. LANGER, and OMID C. FAROKHZAD1
Appeal 2016-008166
Application 12/098,354
Technology Center 1600
Before DONALD E. ADAMS, ERIC B. GRIMES, and
JOHN E. SCHNEIDER, Administrative Patent Judges.
GRIMES, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a dosage
unit formulation, which have been rejected as lacking adequate written
description and as obvious. We have jurisdiction under 35 U.S.C. § 6(b).
We affirm.
1 Appellants identify the Real Parties in Interest as Massachusetts Institute of
Technology; The Brigham and Women’s Hospital, Inc.; Bind Biosciences,
Inc.; and Selecta Biosciences, Inc. (Appeal Br. 2.)
Appeal 2016-008166
Application 12/098,354
STATEMENT OF THE CASE
“Nanoparticles have been developed as vehicles used in the
administration for the delivery of small molecule drugs as well as proteins,
peptide drugs and nucleic acids. The drugs are typically encapsulated or
conjugated in a polymer matrix. ... As the polymer is degraded and/or as
the drug diffuses out of the polymer, the drug is released into the body.”
(Spec. 1:30 to 2:1.) “Targeting controlled release polymer systems (e.g.,
targeted to a particular tissue or cell type or targeted to a specific diseased
tissue but not normal tissue) is desirable because it reduces the amount of a
drug present in tissues of the body that are not targeted.” (Id. at 2:7—10.)
The Specification discloses nanoparticles having poly(amino acid)
targeting moieties that are effective in treating vulnerable plaque, cancer, or
restenosis. (Id. at 3:10-18.) The poly(amino acid) can be, for example, a
glycoprotein, protein, peptidomimetic, affibody, or peptide. (Id. at 3:25—29.)
“The term ‘affibody’ . . . refers to highly specific affinity proteins that can be
designed to bind to any desired target molecule.” (Id. at 29:15—17.)
Claims 1, 2, 4, 7, 8, 13, 15, 16, 20-22, 24, 25, 28, 46-A8, 63, and 82-
84 are on appeal. Claim 1 is illustrative and reads as follows:
1. A dosage unit formulation comprising polymeric target-specific
nanoparticles for use in treating vulnerable plaque, cancer, or restenosis,
comprising an effective amount of a therapeutic, prophylactic or diagnostic
agent for the treatment of vulnerable plaque, cancer, or restenosis,
wherein the nanoparticles have attached thereto poly(amino acid)
targeting moieties that selectively bind (i) collagen in the basement
membrane of a blood vessel attached thereto, (ii) injured vasculature, or (iii)
HER2.
2
Appeal 2016-008166
Application 12/098,354
The claims stand rejected as follows:
Claims 1, 2, 4, 7, 8, 15, 16, 20-22, 24, 25, 28, 46-48, 63, and 82-84
under 35U.S.C. § 112, first paragraph, for lack of adequate written
description (Final Action2 10);
Claims 1, 2, 4, 7, 8, 15, 16, 20-22, 24, 25, 48, 63, and 82—84 under
35 U.S.C. § 103(a) as obvious based on Farokhzad,3 Lanza,4 and Ruoslahti5
(Final Action 22);
Claims 46-48 under 35 U.S.C. § 103(a) as obvious based on
Farokhzad, Lanza, Ruoslahti, and Hoarau6 (Final Action 27);
Claims 25, 28, and 83 under 35 U.S.C. § 103(a) as obvious based on
Farokhzad, Lanza, Ruoslahti, and Duncanson7 (Final Action 28); and
Claim 13 under 35 U.S.C. § 103(a) as obvious based on Farokhzad,
Lanza, Ruoslahti, and Chhatwal8 (Final Action 30).
I
The Examiner has rejected claims 1, 2, 4, 7, 8, 15, 16, 20—22, 24, 25,
28, 46-48, 63, and 82—84 for lack of adequate written description, on the
basis that “[t]he number of polyamino acid targeting species disclosed does
2 Office Action mailed May 15, 2015.
3 Farokhzad et al., US 2005/0037075 Al, published Feb. 17, 2005.
4 Lanza et al., US 2004/0115192 Al, published June 17, 2004.
5 Ruoslahti et al., US 2005/0048063 Al, published Mar. 3, 2005.
6 Hoarau et al., US 2005/0214378 Al, published Sept. 29, 2005.
7 Duncanson et al., Targeted binding ofPLA microparticles with lipid-PEG-
tethered ligands, 28 Biomaterials 4991 4999 (2007).
8 Chhatwal et al., WO 2007/140953 Al, published Dec. 13, 2007.
3
Appeal 2016-008166
Application 12/098,354
not constitute support for a claim to the entire genus of polyamino acid
targeting moieties that are claimed functionally.” (Final Action 11.)
The Examiner finds that “[t]he claims are genus claims, encompassing
any poly(amino acid) of any sequence and length, which functions to
provide desired properties,” and therefore are “extremely broad, in that other
than being a polyamino acid, no structure is required of the targeting
moieties.” (Id. at 12—13.) The Examiner finds that the Specification
describes two peptides, with the sequences ARYLQKLN and AKERC, that
bind respectively to injured vasculature and extracellular basement
membranes, and states that anti-Her2-affibody binds to HER2, although no
structural description is provided for the anti-Her2-affibody. (Id. at 14.)
The Examiner finds that the Specification states that the peptide CREKA
also binds to injured vasculature. (Id. at 16.)
The Examiner also finds that, “[ojther than the particular polyamino
acid sequences . . . AKERC, CREKA, ARYLQKLN or AXYLZZLN,
wherein X and Z are variable amino acids, there do not appear to be any
other particular species of poly(amino acids) disclosed by specific structures
which are effective to achieve the claimed functions.” (Id.) The Examiner
concludes that “[t]he specification does not demonstrate that the applicant
has made a generic invention that achieves the claimed result by showing
that the applicant has invented species sufficient to support a claim to the
functionally-defined genus of polyamino acid targeting moieties,” and does
not show that Appellants were in possession of the claimed invention at the
time the application was filed. (Id. at 18.)
4
Appeal 2016-008166
Application 12/098,354
We agree with the Examiner that a person of ordinary skill in the art
would not have recognized that Appellants were in possession of the claimed
genera based on the written description provided in the Specification.
“[T]he test for sufficiency [of written description] is whether the disclosure
of the application relied upon reasonably conveys to those skilled in the art
that the inventor had possession of the claimed subject matter as of the filing
date.” AriadPharms., Inc. v. EliLilly & Co., 598 F.3d 1336, 1351 (Fed. Cir.
2010). A “sufficient description of a genus instead requires the disclosure of
either a representative number of species falling within the scope of the
genus or structural features common to the members of the genus so that one
of skill in the art can ‘visualize or recognize’ the members of the genus.” Id.
at 1350. “One needs to show that one has truly invented the genus, i.e., that
one has conceived and described sufficient representative species
encompassing the breadth of the genus. Otherwise, one has only a research
plan, leaving it to others to explore the unknown contours of the claimed
genus.” AbbVie Deutschland GmbH & Co. v. Janssen Biotech, Inc., 759
F.3d 1285, 1300 (Fed. Cir. 2014).
Here, claim 1 reads on a formulation comprising nanoparticles with
attached poly(amino acid) targeting moieties that selectively bind to
(i) collagen in the basement membrane of an attached blood vessel, (ii)
injured vasculature, or (iii) HER2. The Specification states that a
“poly(amino acid)” can comprise natural amino acids, unnatural amino
acids, modified amino acids, protected amino acids, or a mimetic of amino
acids. (Spec. 3:25—27.) The Specification also states that a “poly(amino
5
Appeal 2016-008166
Application 12/098,354
acid)” can be a glycoprotein, a protein, a peptidomimetic, an affibody, or a
peptide. (Id. at 3:27—29.)
The scope of the poly(amino acid) targeting moieties encompassed by
claim 1 is therefore very broad. The encompassed targeting moieties can
comprise any of the types of amino acids, and can be any of the types of
amino acid-based compounds, that are recited in the Specification.
The Specification describes five specific targeting moieties: anti-
HER2 affibody, AKERC, CREKA, ARYLQKLN or AXYLZZLN, wherein
X and Z are variable amino acids. (Id. at 4:1 4.) The Specification states
that CREKA and AXYLZZLN (which includes the peptide ARYLQKLN)
bind to extracellular basement membranes under atherosclerotic plaques.
(Id. at 78:31 to 79:9.) The Specification states that AKERC binds to
collagen IV in extracellular basement membranes. (Id. at 82:22—23.)
The Specification does not describe other poly(amino acid) targeting
moieties that bind to HER2 or that bind to extracellular basement
membranes, either attached to a blood vessel or in injured vasculature. We
agree with the Examiner that the limited number of species that are
structurally described in the Specification for the poly(amino acid) targeting
moieties recited in claim 1 are not representative of the full scope of the
recited genera of those moieties.
The Specification does not describe structural features of poly(amino
acid) targeting moieties that are common to those binding to HER2 or those
binding to extracellular basement membranes. Thus, the Specification does
not provide a written description of the recited genera in terms “so that one
of skill in the art can ‘visualize or recognize’ the members of the genus.”
6
Appeal 2016-008166
Application 12/098,354
Ariad, 598 F.3d at 1350. The Specification therefore does not adequately
describe the genera of poly(amino acid) targeting moieties that are recited in
claim 1 adequately to show that Appellants were in possession of the full
scope of the claimed formulation at the time the instant application was
filed.
Appellants argue that the Specification describes the recited
poly(amino acid) targeting moieties at page 29, lines 28—30; Examples 4 and
8; and Figures 19 and 20. (Appeal Br. 12—13.)
We have reviewed the cited portions of the Specification and Figures,
but are not persuaded that they adequately describe the recited genera. The
Specification at page 29, lines 28—30 states that “the invention provides a
nanoparticle conjugated to a poly(amino acid) that selectively targets tumor
vasculature and that selectively binds the alpha 2 chain of collagen IV.” The
Specification’s Example 4 describes the peptide AKERC. (Spec. 81:31 to
83:2.) The Specification’s Example 8 describes “anti-HER-2 [ajffibody.”
(Id. at 89:32.) Figures 19 and 20 both describe the peptide ARYLQKLN.
The cited disclosures therefore describe nothing beyond the particular
species that are discussed above, and that are inadequate to show possession
of the full scope of the recited genera.
In the Reply Brief, Appellants argue that the Examiner erred in
finding that the level of predictability for the claimed targeting moieties is
very low, because “the skilled person would understand the CEAKR peptide
was deliberately used by Appellants as a negative control to demonstrate the
7
Appeal 2016-008166
Application 12/098,354
efficacy of the CREKA peptide to selectively localize the claimed
nanoparticles to collagen IV.” (Reply Br. 7.9)
This argument does not persuade us that the rejection should be
reversed. Regardless of whether the peptide CEAKR would be expected to
direct nanoparticles to collagen IV, claim 1 encompasses, among other
things, any poly(amino acid) targeting moiety that binds to any target in the
collagen of the basement membrane attached to a blood vessel or any target
in injured vasculature. We agree with the Examiner that the Specification’s
examples are inadequate to allow those of ordinary skill in the art to predict
with reasonable assurance which poly(amino acid) targeting moieties other
than those species described in the Specification would bind to the recited
targets.
We therefore affirm the rejection of claim 1 under 35 U.S.C. § 112,
first paragraph. Claims 2, 4, 7, 8, 15, 16, 20-22, 24, 25, 28, 46-48, 63, and
82—84 have not been argued separately and fall with claim 1. 37 C.F.R.
§ 41.37(c)(l)(iv).
9 The Reply Brief also presents new arguments based on the state of the art
at the time of filing and the description of the molecular targets bound by the
recited targeting moieties. (Reply Br. 3—7 and 8—11.) These arguments
were not presented in the Appeal Brief and are not responsive to anything in
the Examiner’s Answer. Therefore, we will not consider them. See
37 C.F.R. § 41.41(b)(2) (“Any argument raised in the reply brief which was
not raised in the appeal brief, or is not responsive to an argument raised in
the examiner’s answer, including any designated new ground of rejection,
will not be considered by the Board for purposes of the present appeal.”).
8
Appeal 2016-008166
Application 12/098,354
II
The Examiner has rejected claims 1, 2, 4, 7, 8, 15, 16, 20—22, 24, 25,
48, 63, and 82—84 as obvious based on Farokhzad, Lanza, and Ruoslahti.
The Examiner finds that “Farokhzad teaches a pharmaceutically acceptable
formulation comprising polymeric target specific nanoparticles comprising a
therapeutic, prophylactic or diagnostic agent.” (Final Action 22.)
The Examiner finds that Farokhzad does not teach a poly(amino acid)
targeting moiety, but Lanza teaches that antibodies, peptides, and nucleic
acids were all “known in the art as targeting moieties and equivalent for the
purpose of improving delivery of therapeutic agent.” (Id. at 24.) The
Examiner concludes that it would have been obvious to modify Farokhzad’s
formulation to include a poly(amino acid) targeting moiety because doing so
would simply require substitution of one known targeting moiety for
another. (Id.)
The Examiner finds that Ruoslahti teaches poly(amino acid) targeting
moieties that selectively bind collagen in the vascular basement membrane.
(Id. at 25.) The Examiner finds that Ruoslahti also teaches that its targeting
moieties home therapeutic agents to vasculature, are useful for improving
cancer treatment, and reduce side effects. (Id.) The Examiner concludes
that these teachings would have led a skilled artisan to modify Farokhzad’s
formulation to include the specific poly(amino acid) targeting moieties
disclosed by Ruoslahti.
We agree with the Examiner that the formulation of claim 1 would
have been obvious based on the cited references. Farokhzad discloses “a
conjugate that includes a nucleic acid ligand bound to a controlled release
9
Appeal 2016-008166
Application 12/098,354
polymer system [and] a pharmaceutical composition that contains the
conjugate.” (Farokhzad 1 8.) Farokhzad states that “[t]he controlled release
polymer system includes an agent such as a therapeutic, diagnostic,
prognostic, or prophylactic agent. The nucleic acid ligand that is bound to
the controlled release polymer system, binds selectively to a target, such as a
cell surface antigen.” (Id.) Farokhzad states that “[t]he nucleic acid ligands
are DNA or RNA oligonucleotides. . . . Like antibodies, nucleic acid ligands
can be prepared that bind to target antigens with high specificity and affinity
and thus can be used as targeting vehicles.” (Id. 112.)
Lanza discloses a composition for delivering a bioactive agent to
targeted tissues or cells that comprises a site-specific targeting ligand.
(Lanza ^fl[ 22—23.) Lanza states that the targeting ligand “bind[s] to
molecular epitopes, ie, receptors, lipids, peptides, cell adhesion molecules,
polysaccharides, biopolymers, and the like.” (Id. 131.) Lanza also states
that a “wide variety of ligands, including but not limited to antibodies,
antibody fragments, peptides, small molecules, polysaccharides, nucleic
acids, aptamers, peptidomimetics, other mimetics and drugs alone or in
combination may be utilized to specifically bind to cellular epitopes and
receptors.” (Id.)
Ruoslahti discloses “a conjugate that contains a therapeutic agent
linked to a homing peptide or peptidomimetic containing the amino acid
sequence CREKA (SEQ ID NO: 1), or a conservative variant or
peptidomimetic thereof, that selectively homes to tumor vasculature and
selectively binds collagen.” (Ruoslahti 111.) More specifically, Ruoslahti
discloses that “a collagen IV alpha-2 chain related polypeptide can act as a
10
Appeal 2016-008166
Application 12/098,354
receptor for the CREKA (SEQ ID NO: 1) tumor homing peptide.” (Id. 151.)
Ruoslahti states that collagen IV is “also known as ‘basement membrane
collagen’ . . . and is found in the basement membrane of virtually all blood
vessels.” (Id. 1 54.)
These disclosures would have made obvious the formulation of claim
1. Farokhzad discloses a formulation like that of claim 1, except that its
nanoparticles include a nucleic acid targeting ligand and Farokhzad does not
disclose a targeting ligand that selectively binds to one of the targets recited
in claim 1. However, Lanza discloses that targeting ligands that bind
molecular epitopes include, among other things, peptides and nucleic acids.
A person of ordinary skill in the art therefore would have understood that a
peptide-based targeting ligand is functionally equivalent to a nucleic acid-
based targeting ligand, and would have reasonably expected that Farokhzad’s
formulation would also selectively bind to its target using a peptide targeting
ligand.
Ruoslahti discloses that the peptide CREKA binds to collagen IV in
the basement membrane of blood vessels, and can direct a therapeutic agent
to tumor vasculature. A skilled artisan therefore would have had reason to
substitute Ruoslahti’s CREKA targeting peptide for the nucleic acid targeting
moiety disclosed by Farokhzad with a reasonable expectation that CREKA
would direct a therapeutic agent to tumor vasculature and be useful in
treating cancer.
Appellants argue that “[njothing in Farokhzad leads one to substitute
polyamino acid ligands for aptamers. Indeed, one is led to believe that
aptamers have greater specificity and affinity than proteins such as
11
Appeal 2016-008166
Application 12/098,354
antibodies, and are therefore preferred. . . . Accordingly, Farokhzad does
not lead one skilled in the art to look for alternative targeting ligands.”
(Appeal Br. 23—24.) Similarly, Appellants argue that “Farokhzad
discourages the use of polypeptides, such as antibodies and antibody
fragments as targeting moieties” and “Lanza does not describe any
advantages of using poly(amino acids) over nucleic acids.” (Id. at 28.)
These arguments are unpersuasive, because the rejection is based on
the combined teachings of Farokhzad, Lanza, and Ruoslahti. As discussed
above, Lanza teaches that peptide-based targeting moieties are functionally
equivalent to the nucleic acid-based targeting moieties specifically taught by
Farokhzad. While Farokhzad teaches that its nucleic acid-based targeting
moieties have some advantages compared to antibodies, the Examiner’s
rejection is based on substituting Ruoslahti’s CREKA peptide, not an
antibody, for Farokhzad’s nucleic acids.
Appellants also argue that “Ruoslahti describes a five amino acid
sequence (specifically, CREKA), which interacts with all forms of collagen,
including helical collagen, non-helical collagen and denatured collagen.”
(Appeal Br. 25.) Appellants specifically argue that, “[bjased on the
definition of ‘collagen’ set forth in paragraph [0009] [sic, 1 56] of Ruoslahti,
the skilled person would understand the disclosure of Ruoslahti does not
describe a ligand that selectively binds collagen in the basement membrane
of a blood vessel, as claimed.” (Id. at 26.)
This argument is also unpersuasive. Ruoslahti expressly states that “a
collagen IV alpha-2 chain related polypeptide can act as a receptor for the
CREKA (SEQ ID NO: 1) tumor homing peptide.” (Ruoslahti 151.)
12
Appeal 2016-008166
Application 12/098,354
Ruoslahti provides a working example demonstrating that “the observed
interaction between CREKA (SEQ ID NO: 1) and the collagen IV fragment
SEQ ID NO: 2 was specific” and concludes that its results “demonstrate that
the CREKA (SEQ ID NO: 1) peptide binds a collagen IV a-2 chain related
protein and further indicate that collagen IV or a related collagen can act as a
receptor for tumor homing molecules in tumor vasculature.” {Id. 135,
142.)
Appellants’ reliance on Ruoslahti’s paragraph 56 does not persuade us
that the CREKA peptide is not specific for collagen IV in the basement
membrane of blood vessels, because paragraph 56 does not expressly
address the binding specificity of CREKA. Rather, paragraph 56 refers to
“[t]he tumor homing molecules useful in the invention.” {Id. ]f 56.) As
discussed above, however, Ruoslahti expressly discloses that CREKA is
specific for collagen IV, also known as “basement membrane collagen.”
{See id. H 51, 54.)
Appellants argue that “formulating polymer/nucleic acid conjugates
requires specific classes of polymers {e.g., non-cationic polymers) in order
to facilitate the interactions required for this system.” (Appeal Br. 29.)
Appellants cite Farokhzad’s disclosure that polymers with a positive surface
charge may decrease specific binding of a nucleic acid ligand to its target.
{Id.) Appellants conclude that “the skilled artisan would recognize from
Farokhzad that polymers that are selected to meet the requirements of the
system including the nucleic acids of Farokhzad would not be same as those
selected to employ the poly(amino acid) targeting elements as claimed.”
{Id.)
13
Appeal 2016-008166
Application 12/098,354
This argument is also unpersuasive. The Examiner’s rejection is
based on replacing the nucleic acid targeting moiety disclosed by Farokhzad
with the CREKA peptide targeting moiety disclosed by Ruoslahti. Thus, a
skilled artisan would have recognized that Farokhzad’s disclosure of
polymers that can be used with nucleic acid targeting moieties would not
apply to nanoparticles having peptide-based targeting moieties. In any
event, Appellants have provided no persuasive basis for concluding that the
polymers that Farokhzad discloses as useful with nucleic acid targeting
moieties would not also be useful with a peptide targeting moiety such as
CREKA.
Appellants also argue that “there is unpredictability in the results one
of ordinary skill in the art would expect in formulating polymer conjugates
for targeting specific tissues” and “the skilled artisan would not have a
reasonable expectation of success in substituting one class of binding
moieties with a different class of moieties.” (Appeal Br. 30.)
This argument is also unpersuasive, because Ruoslahti expressly
discloses that its CREKA peptide “selectively binds collagen,” that CREKA
is a “tumor homing peptide,” and that CREKA “binds a collagen IV a-2
chain related protein.” (Ruoslahti || 11, 51, 142.) Thus, regardless of
whether a skilled artisan would have been able to predict the binding
specificity of other peptides, the cited evidence provides a reasonable basis
for expecting that CREKA would bind to collagen IV in the basement
membrane of blood vessels.
14
Appeal 2016-008166
Application 12/098,354
Finally, Appellants argue that “Simberg[10] . . . describes aNP
[nanoparticle] containing the same peptide sequence CREKA. However,
Simberg shows that the NP-CREKA conjugate targets clotted blood plasma
proteins in tumor stroma and vasculature.” (Appeal Br. 30.) Appellants
conclude that, “[t]aken together, Ruoslahti and Simberg describe an instance
wherein, the conjugation of a ligand known to perform a specific function
(targeting collagen IV) to a NP can result in a different property (targeting
clotted blood plasma proteins).” (Id.)
This argument is also unpersuasive. Simberg does not support
Appellants’ position that attaching a ligand to a nanoparticle can result in
different binding properties. Simberg discloses that “the CREKA peptide
with a fluorescent dye attached . . . bound to clotted plasma proteins in
vitro.'1'’ (Simberg 932, right col.) Simberg describes “coupling] fluorescein-
labeled CREKA . . . onto the surface of 50-nm superparamagnetic, amino
dextran-coated iron oxide (SPIO) nanoparticles.” (Id. at 933, left col.)
Simberg states that “[t]he CREKA-SPIO nanoparticles bound to mouse and
human plasma clots in vitro. . . . These results show that the particle-bound
peptide retains its binding activity toward clotted plasma proteins.” (Id. at
933, left col.)
Thus, Simberg discloses that the binding specificity of the CREKA
peptide is the same regardless of whether it is coupled to a nanoparticle.
Simberg does not support Appellants’ position that conjugating a ligand to a
nanoparticle can result in a different targeting property.
10 Simberg et al., Biomimetic amplification of nanoparticle homing to
tumors, 104 PNAS 932-936 (2007).
15
Appeal 2016-008166
Application 12/098,354
Appellants argue that:
The examiner has identified no art disclosing the additional
features of the targeting moieties of claims 7, 8, and 82.
The examiner has cited no art disclosing blends of functionalized
and non-functionalized polymers with altered rates of clearance
nor having a lipid monolayer or amphiphilic shell, as defined by
claims 83 and 84.
The examiner has cited no art disclosing the agents defined by
any of claims 46, 47 or 48.
Nothing therefore would lead one skilled in the art to any of these
claimed formulations.
(Appeal Br. 27.)
We disagree. Ruoslahti discloses the targeting moiety CREKA,
which is a peptide (claim 8), comprising natural amino acids (claim 7), and
designed to bind to a target molecule (claim 82). Claims 46 and 47 are not
included in this rejection. Regarding claim 48, Ruoslahti discloses that
paclitaxel is suitable for use in its method. (Ruoslahti | 80.) Regarding
claim 83, the Examiner cited Farokhzad’s disclosure at || 98—101, which
discusses PEGylated poly(lactic acid) nanoparticles. (See Final Action 23.)
Appellants’ Specification states that a “polymer (e.g., copolymer, e.g., block
copolymer) containing polyethylene glycol) repeat units is also referred to
as a ‘PEGylated’ polymer. Such polymers . . . lower the rate of clearance
from the circulatory system via the reticuloendothelial system (RES), due to
the presence of the polyethylene glycol) groups.” (Spec. 17:15—20.)
Regarding claim 84, the Examiner finds that “Farokhzad teaches the
nanoparticles comprising an amphiphilic polymer shell, i.e. having a
hydrophilic portion, e.g., PEG, and a hydrophobic portion, e.g., PLA or
16
Appeal 2016-008166
Application 12/098,354
PLGA.” (Ans. 23.) Appellants have not disputed this finding. (See Reply
Br. 11-18.)
Therefore, we affirm the rejection of claims 1, 7, 8, 48, and 82—84
under 35 U.S.C. § 103(a) based on Farokhzad, Lanza, and Ruoslahti.
Claims 2, 4, 15, 16, 20-22, 24, 25, and 63 have not been argued separately
and fall with claim 1. 37 C.F.R. § 41.37(c)(l)(iv).
Ill
The Examiner has rejected claims 46-48 under 35 U.S.C. § 103(a) as
obvious based on Farokhzad, Lanza, Ruoslahti, and Hoarau. We adopt the
Examiner’s findings of fact and reasoning. (See Final Action 27—28.)
Appellants argue that “Hoarau does not cure the deficiencies of
Farokhzad, Lanza and Ruoslahti.” (Reply Br. 18.) However, for the reasons
discussed above, we conclude that Farokhzad, Lanza and Ruoslahti support
the Examiner’s rejection. We therefore affirm the rejection of claims 46-48
under 35 U.S.C. § 103(a) as obvious based on Farokhzad, Lanza, Ruoslahti,
and Hoarau.
IV
The Examiner has rejected claims 25, 28, and 83 under 35 U.S.C.
§ 103(a) as obvious based on Farokhzad, Lanza, Ruoslahti, and Duncanson.
The Examiner finds that, although “Farokhzad, Lanza and Ruoslahti do not
expressly teach wherein the nanoparticle polymeric matrix comprises a lipid
terminated PEG,” “Duncanson teaches polymeric target specific
nanoparticles comprising . . . PLGA . . . and wherein the polymeric matrix
comprises lipid terminated PEG.” (Final Action 29.) The Examiner
17
Appeal 2016-008166
Application 12/098,354
concludes that it would have been obvious to modify the nanoparticles made
obvious by Farokhzad, Lanza, and Ruoslahti to use a polymer matrix
comprising PLGA and lipid-terminated PEG because “lipid terminated PEG
was an art recognized equivalent to the surfactants in the nanoparticles of
Farokhzad. Moreover, lipid terminated PEG was effective for linking the
targeting agent to the nanoparticle and was effective for reducing clearance
of the nanoparticles via the reticuloendothelial system.” (Id.)
We agree with the Examiner that the cited references would have
made obvious the invention of claim 25, which is directed to the formulation
of claim 1, where the nanoparticles comprise a copolymer of PLGA
(polylactic-co-glycolic acid) and polyethylene glycol (PEG). The teachings
of Farokhzad, Lanza, and Ruoslahti are discussed above. Duncanson
discloses “polymeric particles comprised of poly(lactic acid) (PLA) with
incorporated polyethylene glycol)-lipids (PEG-lipids).” (Duncanson 4991,
abstract.)
Duncanson states that “rapid clearance of particles to the
reticuloendothelial system (RES) prevents delivery vehicles from reaching
their designated target site” and “the most effective mitigation of RES-
mediated particle clearance has been accomplished by surface grafting PEG
to build a sterically repulsive shield that protects the particle from
recognition by the RES.” (Id. at 4992, left col.) Duncanson also states that
“a number of groups have incorporated a PEG copolymer in situ during
particle formation. In this process a synthesized diblock copolymer such as
PEG-PLA, PEG-PLGA, or a triblock copolymer such as PLA-PEG-PLA is
directly incorporated.” (Id., citations omitted.) Duncanson discloses that
18
Appeal 2016-008166
Application 12/098,354
“the addition of PEG-lipids lead to a stable emulsion and an easily
suspended final product. ... In contrast to conventionally used detergents,
good biocompatibility and low toxicity of PEG-based lipopolymers is well
documented in the literature.” {Id. at 4994, left col.)
Thus, it would have been obvious to modify the nanoparticles made
obvious by Farokhzad, Lanza, and Ruoslahti to use a polymer matrix
comprising PLGA and lipid-terminated PEG because Duncanson teaches
that PEG-PLGA had been used for such particles by others, and also teaches
that lipid-terminated PEG leads to a stable emulsion, and has good
biocompatibility and low toxicity.
Appellants argue that Duncanson does not teach “selecting a ratio of
functionalized to non-functionalized polymer (claim 83) nor lipid-terminated
PEG (claim 28).” (Appeal Br. 32.)
This argument is unpersuasive because, as discussed above,
Duncanson provides sufficient reason for a person of ordinary skill in the art
to use lipid-terminated PEG in the nanoparticles made obvious by the other
cited references. In addition, claim 83 does not require any particular ratio
of functionalized to non-functionalized polymer. We therefore affirm the
rejection of claims 25, 28, and 83 under 35 U.S.C. § 103(a) based on based
on Farokhzad, Lanza, Ruoslahti, and Duncanson.
V
The Examiner has rejected claim 13 as obvious based on Farokhzad,
Lanza, Ruoslahti, and Chhatwal. Appellants have waived arguments based
on Chhatwal. {See Appeal Br. 33.) We therefore affirm the rejection of
claim 13 under 35 U.S.C. § 103(a) based on Farokhzad, Lanza, Ruoslahti,
19
Appeal 2016-008166
Application 12/098,354
and Chhatwal. See 37 C.F.R. § 41.37(c)(l)(iv) (Appeal Brief must contain
“[t]he arguments of appellant with respect to each ground of rejection, and
the basis therefor.”); Hyatt v. Dudas, 551 F.3d 1307, 1314 (Fed. Cir. 2008).
SUMMARY
We affirm all of the rejections on appeal.
TIME PERIOD FOR RESPONSE
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).
AFFIRMED
20