Wisconsin Alumni Research Foundation

Patent Trials and Appeals Board

Dec 16, 2021

2021000625 (P.T.A.B. Dec. 16, 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.
15/850,416 12/21/2017 Runhui Liu 09824014-P170021US02 5814
60961 7590 12/16/2021
Intellectual Property Dept./DeWitt LLP
Wisconsin Alumni Research Foundation
2 East Mifflin Street,
Suite #600
Madison, WI 53703-2865
EXAMINER
VANHORN, ABIGAIL LOUISE
ART UNIT PAPER NUMBER
1616
NOTIFICATION DATE DELIVERY MODE
12/16/2021 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):
IP-DOCKET@dewittllp.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte RUNHUI LIU, BERNARD WEISBLUM, SAMUEL GELLMAN,
FANG YUN LIM, LESLIE ANNE RANK, NANCY P. KELLER,
JIN WOO BOK, CHRISTINA M. HULL, NAOMI MARIE WALSH, and
MINGWEI HUANG
Appeal 2021-000625
Application 15/850,416
Technology Center 1600
Before ERIC B. GRIMES, TAWEN CHANG, and
RACHEL H. TOWNSEND, Administrative Patent Judges.
TOWNSEND, Administrative Patent Judge.
DECISION ON APPEAL
Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from the
Examiner’s decision to reject claims to an antifungal pharmaceutical
composition of nylon-3 polymers as obvious. We have jurisdiction under
35 U.S.C. § 6(b).
We affirm.

1 We use the word Appellant to refer to “applicant” as defined in 37 C.F.R.
§ 1.42. Appellant identifies the real party in interest as Wisconsin Alumni
Research Foundation. (Appeal Br. 2.)
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STATEMENT OF THE CASE
Appellant’s Specification states that “[n]aturally occurring host-
defense peptides (HDPs) represent one of the first forms of chemical defense
by eukaryotic cells against bacteria, fungi, viruses, and protozoa.” (Spec. 4.)
“[T]hese peptides are usually cationic, amphipathic molecules.” (Id.) “The
targets of most HDPs remain unclear, though some mechanisms of
antifungal HDPs have been reported.” (Id.) “A variety of synthetic, cationic
polymers resembling HDPs have been developed with antibacterial activity
and relatively low toxicity towards eukaryotic cells (human red blood
cells).” (Id.)
According to Appellant’s Specification, “[f]ar fewer examples of
synthetic polymers with selective activity against fungi and minimum
cytotoxicity towards mammalian cells exist.” (Id. at 5.) Appellant’s
invention is directed to nylon-3 polymers present in an amount to inhibit
fungal growth. (Id. at 1.)
Claim 19, reproduced below, is illustrative of the claimed subject
matter:
19. A pharmaceutical composition comprising:
a fungal growth-inhibiting amount of a nylon-3 copolymer having a
formula:

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or a pharmaceutically suitable salt thereof,
wherein:
R1, R3, R4, R5, and R6 are each independently selected from the
group consisting of hydrogen or substituted or unsubstituted C1-C6-
alkyl;
R2 is C1-C6-alkylene;
“A” is hydrogen or an amino-protecting group;
“B” is hydroxyl or a carboxy-protecting group; and
“X,” “Y,” and “Z” are positive numbers;
in combination with a pharmaceutically suitable carrier.
(Appeal Br. Claims Appendix 4–5.)

The prior art relied upon by the Examiner is:
Name Reference Date
R. Liu et al. Tuning the Biological
Activity Profile of
Antibacterial Polymers
via Subunit
Substitution Pattern,
136 J. Am. Chem. Soc.
4410–18
2014
B. Mowery et al. Structure–activity
Relationships among
Random Nylon-3
Copolymers That
Mimic Antibacterial
Host-Defense Peptides,
131 J. Am. Chem. Soc.
9735–45
2009
Kasher et al. US 2014/0238939 A1 Aug. 28, 2014

The following ground of rejection by the Examiner is before us on
review:
Claims 19–26 under 35 U.S.C. § 103 as unpatentable over Liu,
Mowery, and Kasher.
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DISCUSSION
Appellant does not address the claims separately. We select claim 19
as representative.
The Examiner found that Liu teaches an antimicrobial nylon-3
copolymer made from dimethyl (DM) β-lactam and tetramethyl (TM) β-
lactam in a 1:1 ratio having the following formula

(Final Action 4–5.) The Examiner also found that Liu teaches in Figure 1a
that seven β-lactams were used in the study, including not only DM, but
MM with the following structure

(Id. at 5; Advisory Action continuation sheet; Ans. 4.)
The Examiner further found that Liu teaches that antimicrobial nylon-
3 copolymers with a cylochexyl-based β-lactam, CHβ, had been previously
prepared, namely CHβ with MM and CHβ with DM. (Final Action 5; Ans.
4.) The Examiner found that Liu teaches that the previous exploration of
MM and DM CHβ polymers demonstrated that both “proved to be optimal”
with respect to their antibacterial activity. (Final Action 5 (citing Liu 4411,
left column, experimental design).) The Examiner noted, however, that Liu
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teaches that in the present study the CH subunit copolymers were
determined to be toxic to bacteria as well as to hRBC and fibroblasts,
whereas the TM subunit was only toxic to bacteria. (Final Action 5.) The
Examiner noted that Liu teaches that the DM:TM polymer “is only very
weakly hemolytic at high concentrations whereas the other polymers had
significantly higher hemolytic activity.” (Ans. 5 (citing Liu table 1).) Thus,
explained the Examiner, Liu teaches the advantages of the TM monomer
over the CHβ monomer in a nylon-3 copolymer with a cationic-hydrophobic
copolymer structure. (Ans. 4; Final Action 8 (“Page 4411, right column, last
sentence of the first paragraph states that the authors were surprised to
discover that polymers containing the TM subunit displayed superior
properties.”); Advisory Action continuation sheet.)
In addition, the Examiner found that the “desire of Liu . . . is to
provide polymers with lower hemolytic (red blood cell lysis) activity.”
(Ans. 5.) The Examiner concluded from all of the foregoing teachings that
“Liu suggests MM as a cationic subunit,” for use in a nylon-3 copolymer,
although it “does not exemplify nylon-3 copolymers made from MM and
TM.” (Final Action 5; Ans. 4–5.)
Beyond the foregoing, however, the Examiner found that Mowery
provides a further reason that one of ordinary skill in the art would have
found it obvious to substitute MM for DM in a nylon-3 copolymer that
includes TM. In particular, the Examiner found that Mowery teaches
structure-activity relationships of nylon-3 random copolymers that mimic
antibacterial host-defense peptides where polymers that were prepared
included MM subunits or DM subunits. (Final Action 6 (citing Mowery
Figure 7).) The Examiner noted that Mowery teaches when MM was
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replaced with DM, the net lipophilicity of the polymer was altered. (Id.)
The Examiner found that Mowery teaches that “[t]rends suggest that
increasing the overall lipophilicity of the polymer enhances hemolytic
activity (page 9741, left column).” (Id.) In addition, the Examiner found
that Mowery teaches that the DM homopolymer is more hemolytic than the
MM homopolymer. (Id. (citing Mowery Table 1).) In light of the foregoing,
the Examiner found that “the art as a whole . . . suggest[s] the advantages of
replacing DM with MM” in Liu. (Ans. 5; Final Action 6.)
The Examiner also found that there would have been a reasonable
expectation of success in substituting MM for DM in a copolymer with TM.
In particular, the Examiner determined that because the prior art
demonstrated DM was used with TM to make antibacterial polymers and it
is known that MM and DM are homologs differing only by a methyl group,
and because MM and DM were successfully used with CHβ to make
antibacterial polymers, that one of ordinary skill in the art would have
reasonably expected to be able to substitute MM for DM in a nylon-3
copolymer including TM. (Final Action 6; Ans. 6–7.)
Regarding the claim requirement of a carrier and the amount of the
nylon-3 copolymer being a fungal growth-inhibiting amount, the Examiner
found that Liu’s teachings render these limitations obvious for an MM/TM
copolymer. In particular, the Examiner found that Liu “teach[es] solutions
of the polymer[s]” that were made, which “necessarily indicates a carrier is
present.” (Final Action 7.) In addition, the Examiner found that Liu
“teaches [minimum inhibitory] concentrations overlapping with those
exemplified in the instant specification” as being antifungal. (Id.; Ans. 7.)
The Examiner further found that Kasher teaches nylon-3 copolymers
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comprising MM are antimicrobial and have the ability “to prevent, inhibit,
reduce or destroy biofilm-forming microorganisms including bacteria, fungi,
alga[e] or protozoa (paragraphs 0029, 0030 and paragraph 0070).” (Final
Action 7.) Consequently, the Examiner concluded that it would be expected
that the copolymer of MM and TM suggested by Liu and Mowery would
have fungal growth inhibiting properties and one of ordinary skill in the art
would have had “a reasonable expectation of success in forming a
composition comprising a fungal growth-inhibiting amount of the instantly
claimed nylon-3 copolymer.” (Ans. 7; Final Action 7, 9–10.)
We agree with the Examiner’s finding of facts regarding the Liu and
Mowery references as described above and the conclusion of obviousness.
Appellant argues that Liu “literally teaches away from the claims by
explicitly teaching that the cyclohexyl-based monomers are required for
optimal performance.” (Appeal Br. 6.) Appellant contends that the
description of using the MM co-monomer in Liu is restricted to the use in
conjunction with a cyclically constrained co-monomer at 4411 and that Liu’s
DM copolymer structures all include a co-monomer “incorporated into a
ring system” which is a structure that is “outside the scope of the present
claims.” (Appeal Br. 5–6.) We do not find Appellant’s arguments
persuasive.
We do not agree with Appellant that Liu teaches that cyclohexyl-
based monomers are required for optimal performance or that all the DM
copolymer structures explicitly described in Liu included a co-monomer
incorporated into a ring system. Two of the four hydrophobic monomers
used with the cationic subunit DM in the Liu “present study” were not
cyclohexyl based. In particular, diethyl (βDEβ) and tretramethyl (TMβ) β
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lactam monomers were combined with DM. (See Liu 4411.) The structures
of βDEβ and TMβ are set forth below.

Furthermore, it was noted that these hydrophobic β-lactams “should
be comparable in terms of hydrophobicity” to CH-DM and β-cyclopentyl
(βCPβ)-DM nylon-3 polymers “because each contains four side chain
carbon atoms.” (Id.) Liu then notes that “one might have predicted that all
of the new copolymers would have less desirable activity profiles relative to
1:1 DM:CH, because none of the new hydrophobic subunits has a cyclic
constraint on the backbone Cα-Cβ bond” and the Liu authors had “[r]ecently
. . . showed that removing the six-membered ring constraint . . . led to a
substantial (and unfavorable) increase in hemolytic activity along with a
small diminution in antibacterial activity.” (Id.) However, as the Examiner
noted, Liu states that they “were surprised . . . to discover that [the nylon-3]
polymers containing the TM subunit display superior properties” compared
to the DM:CH polymer and that 1:1 DM:TM was the best copolymer. (Id.
4411 and 4414.) In particular, Liu notes that 1:1 DM:TM had similar
antibacterial activities to 1:1 DM:CH, and both were “potent bactericidal
agents,” but 1:1 DM:TM was “only very weakly hemolytic at high
concentrations” and that “the prokaryote-selective biological activity profile
of 1:1 DM:TM is the most favorable among the four copolymers compared
here and among all nylon-3 polymers we have examined.” (Id. at 4411–
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4412, 4414, Tables 1 and 2, and Figure 6.) It was also determined that it
was “difficult for bacteria to develop resistance to” 1:1 DM:TM. (Id. at
4414.)
Liu further notes that data from their study “suggests that polymers
containing a hydrophobic subunit that is expected to be more flexible (βDE)
are more strongly hemolytic than polymers containing isomeric but more
conformationally constrained hydrophobic subunits (TM). (Id. at 4412–13.)
Additionally, Liu notes that their studies with DM:CH and DM:TM lead to
the conclusion “that the superior prokaryote vs eukaryote selectivity of the
DM:TM copolymer arises from the intrinsic properties of the hydrophobic
TM subunit, relative to CH, rather than from variations in subunit
distribution along the polymer chains.” (Id. at 4413.)
In short, Liu teaches that a noncyclohexyl based monomer, TM, was
superior in selectivity to cyclohexyl based monomers while still providing
bactericidal activity. Thus, we do not find persuasive of error Appellant’s
argument that “the two-way combination of Liu et al. with Mowery et al.
describes compounds that are outside the scope of the claims” (Appeal Br.
8).
Furthermore, we agree with the Examiner that the teachings of Liu
and Mowery would have suggested substitution of MM for DM to one of
ordinary skill in the art in a nylon 3 copolymer using the hydrophobic TM
co-monomer. Mowery teaches preparation of nylon-3 polymers using MM
or DM cationic subunits in combination with different cyclic
lipophilic/hydrophobic subunits and studying their activity as compared to
host-defense peptides “and established that membrane lysis is one
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mechanism by which they are likely to act.” (Mowery 9737.) Mowery
states:
In the present study we evaluate the impact of structural
parameters such as lipophilic subunit identity, cationic subunit
identity, lipophilic:cationic proportion, length, and end group
on the antibacterial and hemolytic activities of nylon-3
copolymers.
(Id.)
Mowery teaches that homopolymers of DM and MM “are generally
comparable in antibacterial activity” but the “DM homopolymer is more
hemolytic.” (Id. at 9742.) Mowery “evaluated the impact of varying the
subunits [of copolymers] . . . on biological activity by replacing either MM
or CHx with an analogous β-lactam in the ROP[2] process.” (Id. at 9740.)
“MM was replaced with DM, which bears an additional methyl
substituent.” (Id.) Mowery explains that all of the changes made to both the
cationic and lipophilic/hydrophobic subunits “alter the net lipophilicity of
the resulting polymers, since the analogous β-lactams differ from one
another in the number of methylene units they contain.” (Id.) Mowery
teaches that its study trends “suggest that increasing the overall lipophilicity
of the polymer enhances hemolytic activity.” (Id. at 9741.)
We note that the additional methyl group of DM compared to MM
renders the DM group more lipophilic than the MM group. Given the
teaching of Mowery that increasing the lipophilicity enhances hemolytic
activity, one of ordinary skill in the art would have expected a DM
copolymer as compared to an MM copolymer having the same lipophilic
subunits to be comparatively more hemolytic. Consequently, we agree with

2 ROP stands for ring-opening polymerization. (Id. at 9737.)
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the Examiner that such a teaching in combination with Liu’s teachings of a
DM:TM copolymer where it was determined that of the DM copolymers
made, the copolymer with the TM subunit had the most favorable
prokaryote-selective biological activity profile, would have suggested to one
of ordinary skill in the art that replacing the DM subunit with an MM
subunit would result in an even less hemolytic copolymer.
Furthermore, as discussed, Liu describes making nylon-3 copolymers
having cationic subunits and hydrophobic subunits and provides a list of
seven β-Lactams “used in this study” in Figure 1a, only two of which are
cationic monomers, i.e., DM and MM. Moreover, as the Examiner noted
Liu teaches that it had previously studied antibacterial properties of MM:CH
and DM:CH nylon-3 polymers.
We conclude that the foregoing teachings would have motivated one
of ordinary skill in the art to substitute MM for DM in the Liu DM:TM
polymer in order to provide an even less hemolytic copolymer and still have
comparable antibacterial activity to the DM:TM copolymer. And we
conclude that the teachings of the prior art that MM and DM copolymers are
able to be made with a number of different lipophilic monomers and both
exhibited antibacterial activity (see, e.g., Mowery Figure 8, Liu Tables 1 and
2) would also have given one of ordinary skill in the art a reasonable
expectation of being able to make the MM:TM polymer.
For the foregoing reasons, we do not find persuasive of error
Appellant’s argument that Mowery does not disclose MM:TM polymers or
that Mowery does not “disclose or even remotely suggest a co-polymer
which lacks a cyclically constrained co-monomer” (Appeal Br. 7). The
Examiner’s rejection was not based on the teachings of Mowery alone, but
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rather the combination of Liu and Mowery. “In determining whether
obviousness is established by combining the teachings of the prior art, the
test is what the combined teachings of the references would have suggested
to those of ordinary skill in the art.” In re GPAC Inc., 57 F.3d 1573, 1581
(Fed. Cir. 1995) (internal quotations omitted); In re Gorman, 933 F.2d 982,
986 (Fed. Cir. 1991) (The test of obviousness is “whether the teachings of
the prior art, taken as a whole, would have made obvious the claimed
invention.”).
We now turn to the claim requirement of the nylon-3 copolymer being
present in “a fungal growth-inhibiting amount.” We agree with the
Examiner that Liu teaches MIC concentrations of DM:TM copolymers that
overlap with MIC for MM:TM against certain Candida fungi. (Compare
Spec. Table 8, with Liu Tables 1 and 2 and 4414 (“Further Antibacterial
Studies with 1:1 DM:TM”).) Consequently, we conclude that it would have
been obvious to one of ordinary skill in to arrive at an MM:TM composition
by the substitution of MM for DM in the amounts taught by Liu which
would inherently include a fungal inhibiting amount of the nylon-3
copolymer. Inherency may supply a missing claim limitation in an
obviousness analysis. See, e.g., Santarus, Inc. v. Par Pharm., Inc., 694 F.3d
1344, 1354 (Fed. Cir. 2012); Alcon Research, Ltd. v. Apotex Inc., 687 F.3d
1362, 1369 (Fed. Cir. 2012); In re Kao, 639 F.3d 1057, 1070 (Fed. Cir.
2011); In re Kubin, 561 F.3d 1351, 1357 (Fed. Cir. 2009). “The fact that
[A]ppellant has recognized another advantage which would flow naturally
from following the suggestion of the prior art cannot be the basis for
patentability when the differences would otherwise be obvious.” Ex parte
Obiaya, 227 USPQ 58, 60 (BPAI 1985).
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Although it may be the case that one of ordinary skill in the art would
not have recognized the amount was anti-fungal, such recognition is not
necessary to establish the property was inherent to the composition. “[T]he
discovery of a previously unappreciated property of a prior art composition,
or of a scientific explanation for the prior art’s functioning, does not render
the old composition patentably new to the discoverer.” Atlas Powder Co. v.
IRECO Inc., 190 F.3d 1342, 1347 (Fed. Cir. 1999); see also Abbott Labs. v.
Baxter Pharm. Products, Inc., 471 F.3d 1363, 1367 (Fed. Cir. 2006) (“[A]
reference may anticipate even when the relevant properties of the thing
disclosed were not appreciated at the time.”).
Thus, we affirm the Examiner’s rejection of claim 19 as being obvious
from the teachings of Liu and Mowery. That we do not rely on Kasher to
affirm the Examiner does not require we designate the affirmance as a new
ground of rejection. In re Bush, 296 F.2d 491, 496 (CCPA 1961).
Moreover, the Examiner noted the inherency aspect that we rely on. (Final
Action 7; Ans. 7.) Claims 20–26, which have not been argued separately,
fall with claim 19. 37 C.F.R. § 41.37(c)(1)(iv).
DECISION SUMMARY
In summary:
Claims
Rejected
35 U.S.C.
§
Reference(s)/Basis Affirmed Reversed
19–26 103 Liu, Mowery,
Kasher
19–26

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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). See 37 C.F.R.
§ 1.136(a)(1)(iv).
AFFIRMED