INTERNATIONAL BUSINESS MACHINES CORPORATION et al.

Patent Trials and Appeals Board

Jun 9, 2021

2020005888 (P.T.A.B. Jun. 9, 2021)

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.
15/397,193 01/03/2017 Kazuki Fukushima ARC920090079US2 1371
93453 7590 06/09/2021
Michael R. Roberts
4912 Buckline Crossing
Atlanta, GA 30338
EXAMINER
POPA, ILEANA
ART UNIT PAPER NUMBER
1633
NOTIFICATION DATE DELIVERY MODE
06/09/2021 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):
MRoberts@MRRPatents.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte KAZUKI FUKUSHIMA,
JAMES L. HEDRICK, and YI YAN YANG
__________

Appeal 2020-005888
Application 15/397,193
Technology Center 1600
__________

Before DONALD E. ADAMS, JEFFREY N. FREDMAN, and
TAWEN CHANG, Administrative Patent Judges.

FREDMAN, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal1 under 35 U.S.C. § 134 involving claims to a
polymer complex for use in gene therapeutics and drug delivery. The
Examiner rejected the claims as obvious. We have jurisdiction under 35
U.S.C. § 6(b). We reverse.

1 We use the word “Appellant” to refer to “applicant” as defined in 37
C.F.R. § 1.42. Appellant identifies the real parties in interest as International
Business Machines Corporation and the Agency for Science, Technology,
and Research (see Appeal Br. 3). We refer to the Specification of Jan. 3,
2017 (“Spec.”); Final Action of Jan. 3, 2020 (“Final Act.”); Appeal Brief of
Mar. 4, 2020 (“Appeal Br.”); Examiner’s Answer of June 26, 2020 (“Ans.”);
and Reply Brief of Aug. 14, 2020 (“Reply Br.”).
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Statement of the Case
Background
“Recent advances in gene therapeutics have lead to a critical need for
a broader selection of less expensive, non-cytotoxic carrier materials for
gene transfection” (Spec. ¶ 2). “Non-viral vectors include . . . [c]ationic
polymers and cationic lipids [that] can bind electrostatically to negatively
charged genetic material to form a carrier-gene complex having decreased
net charge” (id. ¶ 3). “[H]owever this tight packing also presents a problem
in the unpacking of genes” (id. ¶ 5). “A continued need exists for less
expensive, less cytotoxic, more biodegradable synthetic carriers for gene
transfection and drug delivery” (id. ¶ 6).
The Claims
Claims 1–4, 8–10, 14–17, and 19–24 are on appeal. Independent
claim 1 is representative and reads as follows:
1. A polymer complex, comprising:
a negatively charged biologically active material selected
from the group consisting of genes, nucleotides, proteins,
peptides, drugs, and combinations thereof;
and
a biodegradable cationic polymer comprising two
polymer chains joined by a divalent linking group, wherein
each of the polymer chains comprises
i) a first repeat unit selected from the group consisting of:
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ii) an optional second repeat unit;
wherein
the biologically active material and the cationic polymer
are bound together by non-covalent interactions, and the
polymer complex is capable of entering a cell by endocytosis
and releasing the biologically active material within the cell.
The Issues
The Examiner rejected claims 1–4, 8–10, 14–17, and 19–22 under 35
U.S.C. § 103(a) as obvious over Tyson,2 Zhang,3 Pratt,4 Vroman,5

2 Tyson et al., Degradable Porous Scaffolds from Various L-Lactide and
Trimethylene Carbonate Copolymers Obtained by a Simple and Effective
Method, 10 Biomacromolecules 149–54 (2009).
3 Zhang et al., Trimethylene carbonate-based polymers for controlled drug
delivery applications, 116 J. Controlled Release e28–29 (2006).
4 Pratt et al., Tagging alcohols with cyclic carbonate: a versatile equivalent
of (meth)acrylate for ring-opening polymerization, 114 Chem. Comm. 114–
16 (2008).
5 Vroman et al., Copolymers of ε-caprolactone and quaternized
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Nifant’ev,6 and Trolssas7 (Final Act. 3–6).
The Examiner rejected claims 1–4, 8–10, 14–17, and 19–24 under 35
U.S.C. § 103(a) as obvious over Tyson, Zhang, Pratt, Vroman, Nifant’ev,
Trolssas, and Niidome8 (Final Act. 6).
Because both of these rejections share the same issues and prior art,
we will consider these rejections together.
The issues with respect to this rejection are:
(i) Does a preponderance of the evidence of record support the
Examiner’s conclusion that the prior art renders the claims obvious?
(ii) If so, has Appellant provided evidence of unexpected results that
outweighs the evidence supporting the prima facie case of obviousness?
Findings of Fact
1. Tyson teaches “six different poly(L-lactide-co-trimethylene
carbonate) (poly(LLA-co-TMC)) copolymers with different LLA and TMC
contents and molecular weights were synthesized” using “bulk
polymerizations in which Sn(Oct)2 and ethylene glycol were used” (Tyson
150, col. 1).

ε-caprolactone as gene carriers, 118 J. Controlled Release 136–44 (2006).
6 Nifant’ev et al., Cationic Nitrophospoamphiphiles of Phosphonate and
Amidophosphonate Types, 41 Russian J. Organic Chemistry 1116–21
(2005).
7 Trollsås et al., Versatile and Controlled Synthesis of Star and Branched
Macromolecules by Dentritic Initiation, 30 Macromolecules 8508–11
(1997).
8 Niidome et al., Gene Therapy Progress and Prospects: Nonviral Vectors, 9
Gene Therapy 1647–52 (2002).
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2. Zhang teaches “[m]icroparticles, nanospheres, and micellar-like
nanoparticles based on PTMC and mPEG–PTMC amphiphilic copolymers
were prepared” (Zhang e28, col. 1).
3. Zhang teaches “block copolymers of PTMC with monomethoxy
poly(ethylene glycol) (Mn = 3000, mPEG3) were synthesized by ring-
opening polymerization using Sn0ct2 as a catalyst” (Zhang e28, col. 1).
4. Zhang teaches “[d]examethasone was loaded into PTMC and
mPEG3–PTMC11 nanospheres at a highest efficiency of respectively 54%
and 88% using the salting out method, and of respectively 91%, and 72%
using the single emulsion method. The release of dexamethasone was
sustained and diffusion controlled” (Zhang e29, col. 1).
5. Vroman teaches a
nanoparticulate delivery system consisting of poly(ε-
caprolactone) (PCL) bearing pendant pyridinium groups, as a
non-viral gene delivery vector. Copolymers of ε-caprolactone
(CL) and γ-bromo-ε-caprolactone (BrCL) were prepared with a
statistical and a blocky structure, and the bromide pendant
groups were quaternized by pyridine. These copolymers fulfill
requirements for transfection of plasmid DNA.
(Vroman 136, col. 2).
6. Vroman teaches “cytotoxicity of copolymers was mainly due to
the presence of pyridinium groups since poly(ε-caprolactone) polymer alone
was much less cytotoxic” (Vroman 142, col. 1).
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7. Figure 7 of Vroman is reproduced below:

Fig. 7. Transfection efficiency of copolymers/DNA complexes
in HeLa cells. HeLa cells were seeded at a density of
104cells/well in 96-well plate and transfection was performed at
a dose of 1μg of DNA for all groups and analysed at 48 h after
transfection. The luciferase expression in relative light units
(RLU) is normalized to mg of cellular protein (n=3).
(Vroman 142, col. 1).
8. Figure 8 of Vroman is reproduced below:

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“Fig. 8. Cytotoxicity of copolymers/DNA complexes to HeLa cells. The
MTT dye reduction assay was performed 48 h after incubation of the cells
with the same amount of the preparations as in the transfection trial (n=6)”
(Vroman 142, col. 2).
9. Pratt teaches “general synthetic route to incorporate a broad
range of functional groups into cyclic carbonate monomers has been
developed. These monomers can be polymerized under mild, one-pot
conditions to create random or block copolymers” (Pratt 115, col. 2). Pratt
teaches “conversion to the acyl chloride using oxalyl chloride followed by
reaction with the alcohol or amine in the presence of base” (id. at 114, col.
1).
Principles of Law
A prima facie case for obviousness “requires a suggestion of all
limitations in a claim,” CFMT, Inc. v. Yieldup Int’l Corp., 349 F.3d 1333,
1342 (Fed. Cir. 2003) and “a reason that would have prompted a person of
ordinary skill in the relevant field to combine the elements in the way the
claimed new invention does.” KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398,
418 (2007).
Analysis
Prima Facie Obviousness
The Examiner finds it “obvious to modify the teachings of Tyson et
al. by formulated their polymer into nanoparticles to achieve the predictable
result of obtaining a composition suitable for the intracellular delivery of
proteins and/or drugs” (Final Act. 3). The Examiner further finds that:
Based on the combined teachings of Vroman et al., Nifant’ev et
al. and Pratt et al., one of skill in the art would have readily
recognized that monomers 1c and 1i taught by Pratt et al. could
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be used to introduce quaternary amines into the polymer of
Tyson et al. to obtain a polymer suitable to be used as a gene
carrier. One of skill in the art would have found obvious to
replace the cyclic monomer PLL with the cyclic carbonate
monomers 1c or 1i in the ROP method of Tyson et al. to
achieve the predictable result of obtaining a di block copolymer
comprising two poly(1c-TMC) or poly(1i-TMC) chains linked
via ethylene glycol a polymer.
(id. at 4).
Appellant contends “the combination of cited references of the
rejection do not enable any cationic aliphatic polycarbonate and do not
disclose, teach, or suggest any gene delivery or cytotoxicity properties of a
cationic polycarbonate” (Appeal Br. 16). Appellant also contends “[d]ue to
its hydrophobicity, the TYSON polymer cannot form a polymer complex
with a biologically active material ‘capable of entering a cell by endocytosis
and releasing the biologically active material within the cell’” (Reply Br. 2).
We find that Appellant has the better position because the Examiner’s
reasons for combining are conclusory. That is, the Examiner provides no
persuasive explanation as to why an ordinary artisan would modify a
polymer used for bioscaffolds as in Tyson to generate a polymer complex
with biologically active materials that “is capable of entering a cell by
endocytosis and releasing the biologically active material within the cell” as
required by claim 1. It is not sufficient for an Examiner to simply state that
a modification could be made, it is necessary to provide “a reason that would
have prompted a person of ordinary skill in the relevant field to combine the
elements in the way the claimed new invention does.” KSR, 550 U.S. at 418.
No such reason was given here.
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Similarly, no persuasive reason was given in the Examiner’s rejection
based on Vroman, Nifant’ev, Pratt, and Trollsas that explained why the other
modifications necessary to obtain the polymers of claim 1 would have been
obvious. “It is impermissible to use the claimed invention as an instruction
manual or ‘template’ to piece together the teachings of the prior art so that
the claimed invention is rendered obvious.” In re Fritch, 972 F.2d 1260,
1266 (Fed. Cir. 1992).
Lastly, the Examiner provides no evidence that the polymer of Tyson
is even capable of entering a cell, as required by claim 1. While we do not
rely heavily upon Appellant’s bare contention that Tyson would not
function, the Examiner’s burden in that regard was to show a reasonable
expectation of success in making the proposed changes and no persuasive
evidence of such expectation was provided.
Secondary Considerations
Because we find that the Examiner has not established a prima facie
case of obviousness, we need not address the argued unexpected results.9
Conclusions of Law
(i) A preponderance of the evidence of record does not support the
Examiner’s conclusion that the prior art renders the claims obvious.
(ii) We do not reach the secondary consideration arguments because
there is not a prima facie case of obviousness.

9 We do note that Appellant did not identify evidence in the Specification or a
Declaration identifying the results as unexpected or surprising, did not establish that
the results were commensurate in scope with the claims, did not establish that the
comparison was valid given the use of different cell lines, and did not establish that
the results were different in kind and not merely in degree.
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DECISION SUMMARY
In summary:
Claims
Rejected
35 U.S.C.
§
Reference(s)/Basis Affirmed Reversed
1–4, 8–10,
14–17, 19–22
103(a) Tyson, Zhang,
Pratt, Vroman,
Nifant’ev, Trolssas
1–4, 8–10,
14–17,
19–22
1–4, 8–10,
14–17, 19–24
103(a) Tyson, Zhang,
Pratt, Vroman,
Nifant’ev,
Trolssas, Niidome
1–4, 8–10,
14–17,
19–24
Overall
Outcome
1–4, 8–10,
14–17,
19–24

REVERSED