Bo Liang et al.

Patent Trials and Appeals Board

Jul 29, 2019

14127846 - (D) (P.T.A.B. Jul. 29, 2019)

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.
14/127,846 03/14/2014 Bo Liang 146660-010400 1726
160605 7590 07/29/2019
Venture Partner, LLC
Weisun Rao
401 N. Michigan Ave.
Suite 1200
Chicago, IL 60611
EXAMINER
LIU, SUE XU
ART UNIT PAPER NUMBER
1616
NOTIFICATION DATE DELIVERY MODE
07/29/2019 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):
chen@venturepartnerllc.com
ipmail@venturepartnerllc.com
rao@venturepartnerllc.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte BO LIANG, BELACHEW TESSEMA, JOSEPH A. CAPRIOTTI,
MICHAEL C. SAMSON, and WEI SONG1
__________

Appeal 2018-004521
Application 14/127,846
Technology Center 1600
__________

Before ERIC B. GRIMES, DEBORAH KATZ, and RYAN H. FLAX,
Administrative Patent Judges.

GRIMES, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a
pharmaceutical composition, which have been rejected as obvious. We have
jurisdiction under 35 U.S.C. § 6(b).
We affirm.
STATEMENT OF THE CASE
The Specification states that “[i]odine and steroid[s] have both been
used in treating nasal conditions or diseases.” Spec. ¶ 10. The Specification

1 Appellants identify the Real Party in Interest as IVEIW Therapeutics, Inc.
Br. 2.
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also states that “[i]t has been widely known that iodine or iodine-releasing
agents . . . are incompatible with most steroid preparations due to the high
potential for chemical reactivity between molecular iodine and steroid
moieties. As a result, these agents must be made from separate solutions,
administered independently.” Id.
The Specification discloses that,
[t]hough the reactivity of iodine with steroids is
well known, the pharmaceutical compositions of this
invention are surprising[ly] stable, as the steroids
contained therein (e.g., mometasone, fluticasone,
budesonide, or a salt or adduct thereof) have been able to
resist iodination, iodine oxidation and iodine-catalyzed
addition reactions.
Id. ¶ 13.
Claims 1–5, 7–15, 19–21, and 23 are on appeal. Claim 1 is
representative and reads as follows:
1. A pharmaceutical composition for treating a sinus disease
or infection of a patient comprising an iodine-containing compound
and a steroid, wherein the steroid comprises fluticasone or
budesonide, or a salt or ester thereof.

The claims stand rejected as follows:
Claim 3 under 35 U.S.C. § 112, second paragraph, as indefinite (Final
Action2 2);
Claims 1–5, 7–14, and 23 under 35 U.S.C. § 103(a) as obvious based
on Leshchiner3 and Cagle4 (Final Action 4);

2 Office Action mailed Dec. 9, 2016.
3 Leshchiner et al., US 2006/0280809 A1, published Dec. 14, 2006.
4 Cagle et al., WO 00/18404, published Apr. 6, 2000.
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Claim 15 under 35 U.S.C. § 103(a) as obvious based on Leshchiner,
Cagle, and Haslwanter5 (Final Action 10); and
Claims 19–21 under 35 U.S.C. § 103(a) as obvious based on
Leshchiner, Cagle, and Lulla6 (Final Action 12).
I
The Examiner rejected claim 3 as indefinite, because it “recites the
terms ‘organic polymer’, ‘polyol’, ‘surface active anion’, and ‘cation’, the
scope of said terms is unclear. One of ordinary skill in the art would not
have been readily aware of the scope of said terms or said claim.” Final
Action 3.
Appellants filed an amendment canceling claim 3,7 but the
amendment was not entered.8 Appellants did not address this rejection in the
Appeal Brief or Reply Brief. Because Appellants have waived their
arguments with respect to this rejection, we affirm it. See 37 C.F.R.
§ 41.37(c)(1)(iv); Hyatt v. Dudas, 551 F.3d 1307, 1314 (Fed. Cir. 2008)
(“When the appellant fails to contest a ground of rejection to the Board, . . .
the PTO may affirm the rejection of the group of claims that the examiner
rejected on that ground without considering the merits of those rejections.”).

5 Haslwanter et al., US 6,565,832 B1, issued May 20, 2003.
6 Lulla et al., US 8,163,723 B2, issued Apr. 24, 2012.
7 Response to Final Office Action, filed March 8, 2017.
8 Advisory Action mailed March 23, 2017 (indicating “rejected” for the
status of claim 3).
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II
The Examiner has rejected claims 1–5, 7–14, and 23 as obvious based
on Leshchiner and Cagle. The Examiner finds that “Leshchiner et al. teach
iodine based compositions for nasal use comprising an anti-inflammatory
(abstract).” Final Action 5. The Examiner also finds that Leshchiner’s
composition can comprise steroid anti-inflammatories, but Leshchiner does
not disclose budesonide or fluticasone for use in its composition. Id.
The Examiner finds, however, that “Cagle et al. teach nasal
compositions comprising antibiotics in combination with anti-inflammatory
agents (abstract), specific steroidal anti-inflammatory agents including
budesonide and fluticasone (page 7).” Id. The Examiner concludes that it
would have been obvious
to produce the formulations of Leshchiner et al. with
0.01–1% budesonide or fluticasone as taught by Cagle et
al. . . . because both references are drawn to
pharmaceutical nasal formulations comprising an
antibiotic in combination with a steroidal anti-
inflammatory and Cagle et al. teach specific anti-
inflammatory agents and percentages thereof that may be
utilized.
Id. at 6.
We agree with the Examiner that the formulation of claim 1 would
have been prima facie obvious based on Leshchiner and Cagle. Leshchiner
states that “[o]tic and nasal infections are often accompanied by
inflammation and pain in the infected otic and nasal tissues.” Leshchiner
¶ 11. Leshchiner states that “[t]here is a need for otic and nasal
pharmaceutical compositions that combine the broad anti-infective activity
of iodine-based compounds with the anti-inflammatory and analgesic
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activity of natural and synthetic oils and extracts as well as steroidal and
non-steroidal anti-inflammatory agents.” Id.
Leshchiner discloses “topical antimicrobial, non-antibiotic,
pharmaceutical compositions for the treatment of otic and nasal infections.
. . . The compositions are based on the use of polyvinlypyr[r]olidone-iodine
(PVP-I).” Id. ¶ 30. “The compositions of the present invention may also
contain one or more anti-inflammatory, analgesic and antiseptic agents.” Id.
¶ 31. In a specific embodiment, Leshchiner discloses a topical
pharmaceutical composition comprising PVP-I, an excipient, and a vehicle
(claim 1), and further comprising an anti-inflammatory agent (claim 9),
wherein the anti-inflammatory agent is cortisone or acetaminophen (claim
10). Cortisone is a steroid. Spec. ¶ 56.
Leshchiner does not disclose budesonide or fluticasone as the
steroidal anti-inflammatory agent in its composition. However, like
Leshchiner, Cagle teaches that “nasal infections are frequently accompanied
by inflammation of the infected . . . nasal tissues.” Cagle 2:18–19. “Thus,
there is also a need for . . . nasal pharmaceutical compositions that combine
the anti-infective activity of one or more antibiotics with the anti-
inflammatory activity of one or more steroid or non-steroid agents in a
single composition.” Id. at 2:21–24.
Cagle discloses “the use of a potent new class of antibiotics to treat
. . . nasal infections.” Id. at 2:28–29. “The compositions preferably also
contain one or more anti-inflammatory agents to treat inflammation
associated with infections of . . . nasal tissues.” Id. at 3:5–6. “The anti-
inflammatory agents utilized in [Cagle’s] invention are broadly classified as
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steroidal or non-steroidal. The preferred steroidal anti-inflammatory agents
are glucocorticoids.” Id. at 7:13–15. “The preferred glucocorticoids for nasal
use include mometasone, fluticasone, beclomethasone, flunisolide,
triamcinolone and budesonide.” Id. at 7:18–20.
Based on these teachings, it would have been obvious to include
budesonide or fluticasone, along with the PVP-I in Leshchiner’s composition.
The references provide ample reason to make the combination, because both
are directed to compositions for treating nasal infections, both contain an
anti-infective agent (PVP-I in Leshchiner, an antibiotic in Cagle), both
suggest including a steroidal anti-inflammatory agent in the composition,
Leshchiner discloses a specific embodiment comprising cortisone, and Cagle
discloses budesonide and fluticasone as preferred steroidal anti-inflammatory
agents for nasal use. A skilled artisan would have had a reasonable
expectation of success in making the combination because both references
describe their compositions as suitable for treating nasal infections.
Appellants argue that “other than the general mentioning of steroidal
and non-steroidal anti-inflammatory agents in Paragraph [0011] in the
‘Description of the Related Art’, nowhere else has Leshchiner specifically
mentioned any anti-inflammatory agent, be it steroidal or nonsteroidal.”
Br. 4.
This argument is unpersuasive, because Leshchiner describes
compositions comprising either a steroidal (cortisone) or non-steroidal
(acetaminophen) anti-inflammatory agent. Leshchiner, claim 10. Even
without that specific disclosure, however, Leshchiner’s express suggestion
to include “anti-inflammatory . . . agents” in its composition, Leshchiner
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¶ 31, would be sufficient reason to include an anti-inflammatory agent
known for use in compositions for treating nasal infections.
Appellants also argue that they “carried out experiments to prepare
compositions containing PVP-I and ketorolac tromethamine, a well-known
and popular non-steroidal anti-inflammatory agent. The results show that
PVP-I readily reacted with ketorolac tromethamine.” Br. 5.
This argument is unpersuasive, because it is unsupported by any
objective evidence. Appellants, in the brief, state results that were
purportedly obtained in the ketorolac experiments, but no data are provided,
nor is any citation to a part of the record describing the actual experiments.
The results set out in the Appeal Brief therefore amount to nothing more
than attorney argument. 9 In addition, Appellants do not explain why the
results found for a non-steroidal anti-inflammatory agent would be
predictive of results expected for the steroidal agents budesonide and
fluticasone.
Appellants also argue that, “as Cagle requires its compositions
contain antibiotics, whereas Leshchiner is silent on antibiotics, these two
references essentially require the opposites.” Br. 5.
This argument is also unpersuasive. Both Leshchiner and Cagle
disclose that their compositions are useful for treating nasal infections and

9 Appellants later state that “[t]he data from the test with the non-steroidal
anti-inflammatory agent, i.e., ketorolac tromethamine, were presented on
page 7, last paragraph, in Applicant’s initial response to the Final Office
Action filed on March 8, 2017.” Br. 9. The cited passage, however, is also
attorney argument and does not include data supporting the purported
results.
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contain an antimicrobial agent. Leshchiner ¶ 30, Cagle 7:5–7. The references
use different antimicrobial agents, but they do not “require the opposites,” as
Appellants argue.
Appellants argue that “it had been well known in the art that iodine
would react with olefin bonds in a steroid backbone even under mild
conditions and a person skilled in the art would not have combined the
teachings of Leshchiner and Cagle.” Br. 6. Appellants cite to three
references submitted during prosecution and included as Exhibits A
(“Woodward”),10 B (“Ellington”),11 and C (”Overton”)12 in the Evidence
Appendix of the Appeal Brief.
We have considered the cited references, but find that they do not
support the position that a skilled artisan would have expected the PVP-I in
Leshchiner’s composition to react with budesonide or fluticasone.
Woodward describes cis-hydroxylation of a steroid intermediate. Woodward
209, title. Woodward states that, when the intermediate “is treated in acetic
acid with iodine (1.05 equivalents), silver acetate (2.25 equivalents) and
water (1.0 equivalent) and finally heated at 90–95° for three hours, oxidation
of the 6,7-double bond occurs.” Id. at 209–210. Appellants have provided no
basis for concluding that the reaction conditions described by Woodward,

10 R. B. Woodward & F. V. Brutcher, Jr., cis-Hydroxylation of a Synthetic
Steroid Intermediate with Iodine, Silver Acetate and Wet Acetic Acid,
unidentified journal, vol. 80, pp. 209–211 (1958).
11 P. S. Ellington et al., Hydroxy-Steroids. Part VI. Reactions of Olefins with
Silver Salts and Iodine. J. Chem. Soc. C. 1327 (1966) (abstract only).
12 Steroid Properties and Reactions, Terpenoids and Steroids, K.H. Overton
(ed.), page 297 (1971).
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including the presence of acetic acid and silver acetate, are similar to the
conditions that would result from using budesonide or fluticasone as the
steroidal anti-inflammatory agent in Leshchiner’s composition. Thus,
Appellants have not shown that a skilled artisan would have expected
Woodward’s reaction to occur if the teachings of Leshchiner and Cagle were
combined.
Ellington describes “[m]ild conditions . . . for carrying out the
Woodward cis-hydroxylation of olefinic bonds.” Ellington, abstract.
Although Ellington does not fully describe the reaction conditions, it makes
clear that all of the reactions include a silver compound. Id. Again,
Appellants have not explained why a skilled artisan would have expected the
reactions described by Ellington to occur if budesonide or fluticasone was
used in Leshchiner’s composition.
Overton describes a reaction involving “iodine azide (IN3), which
readily attacks olefinic steroids . . . to give iodo-azides.” Exhibit C 297.
Leshchiner’s composition, however, comprises PVP-I as the iodine-releasing
agent, not iodine azide. Appellants have not explained why Overton’s
reaction would be predictive of the effect of using budesonide or fluticasone
in Leshchiner’s composition.
In summary, Appellants’ evidence does not support a conclusion that
a person of ordinary skill in the art would have expected the PVP-I in
Leshchiner’s composition to react with the budesonide or fluticasone
suggested by Cagle as preferred steroidal anti-inflammatory agents.
Appellants argue that “the affinity of free iodine (I2) for reaction with
-OH, -SH, and -NH functional groups is well described in the literature and
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forms the basis for the anti-microbial activity of iodine-containing solutions.
See, e.g., H. Rackur et al., J. Hosp. Infect., 1985; 6: 13–23 (copy attached as
Exhibit D) and references therein.” Br. 7.
Appellants, however, do not point to any specific disclosure in Rackur
that supports their position, and we decline to speculate on what disclosure
Appellants intend to rely on in the Rackur reference or in the “references
therein.” Thus, Appellants have not identified any specific evidence
supporting their argument that a skilled artisan would have expected the -OH
groups in budesonide to react with the iodine released from Leshchiner’s
PVP-I.
Appellants argue that “the compositions of claim 1 of the present
invention have proven to be unexpectedly stable.” Br. 7. Appellants point
to “[s]tability test data described in the present application, starting at
Paragraph [0069] through Paragraph [0080], including Tables 1–10” as
“show[ing] that the compositions of claim 1 . . . are unexpectedly and
remarkably stable, even at a high temperature of 60 °C.” Id. Appellants
argue that the Liang Declaration13 “shows the head-to-head comparison of
one of the two steroidal anti-inflammatory agents specifically recited in
claim 1, against another steroid that is not within the claim scope of the
present application. Unexpected results in stability of the compositions were
shown by the test with budesonide.” Id. at 9.
Appellants also argue that “the compositions of claim 1 of the present
invention have been observed to be much more homogenous than the control

13 Declaration under 37 C.F.R. § 1.132 of Bo Liang, filed June 8, 2017.
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samples, illustrating that budesonide unexpectedly became much more
soluble due to the addition of PVP-I to the compositions of claim 1.” Id. at
8. “Lastly [Appellants argue], the compositions of claim 1 . . . have also
shown unexpected therapeutic effects, as described in Examples 8–10 of the
present application (Paragraphs [0081]–[0098], including Tables 11–15).”
Id.
We have considered the cited evidence but are not persuaded that it
supports a conclusion that the claimed composition would have been
nonobvious. Appellants assert three unexpected properties for the claimed
compositions: stability, solubility, and therapeutic effect. Regarding
stability, Appellants point to the Specification’s paragraphs 69–83 and
Tables 1–10, as well as the Liang Declaration. Br. 7–9. Collectively, the
cited material shows that a mixture of PVP-I and budesonide is storage-
stable to varying degrees under different conditions, and is more storage-
stable than a mixture of PVP-I and dexamethasone sodium phosphate (a
steroidal anti-inflammatory agent outside the scope of the claims).
However, “[t]o be particularly probative, evidence of unexpected
results must establish that there is a difference between the results obtained
and those of the closest prior art, and that the difference would not have
been expected by one of ordinary skill in the art at the time of the
invention.” Bristol-Myers Squibb Co. v. Teva Pharms. USA, Inc., 752 F.3d
967, 977 (Fed. Cir. 2014) (emphasis added).
Here, the claimed composition is closest to the prior art composition
defined by Leshchiner’s claim 10, which comprises PVP-I and cortisone as
the steroidal anti-inflammatory agent. Appellants’ data do not show that the
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storage stability of the claimed composition is unexpectedly superior to that
of the closest prior art composition, and therefore do not show that the
claimed composition would not have been obvious in view of the prior art.
Appellants’ evidence regarding the solubility of budesonide in the
claimed composition suffers from the same defect. The Specification states
that in an accelerated degradation test, the budesonide/PVP-I sample
“showed a comparable stability with the control [no PVP-I] sample, but
during the test, it is surprising that we observed that the sample was much
more homogeneous than the control. This illustrated the solubility of the
budesonide was significantly improved by addition of PVP-Iodine.” Spec.
¶ 76. The data, however, do not compare the solubility of budesonide to that
of the closest prior art, Leshchiner’s cortisone/PVP-I composition. Lacking a
comparison to the closest prior art, Appellants’ data do not show that the
claimed composition would not have been obvious in view of the prior art.
Regarding therapeutic effect, Appellants point to “Examples 8–10 of
the present application (Paragraphs [0081]–[0098], including Tables 11–15).”
Br. 8. The Specification’s Example 8 (¶¶ 77–83) compares the effect of a
formulation comprising PVP-I and budesonide against Staphylococcus
aureus and Pseudomonas aeruginosa. The control in that experiment is
saline. Id. ¶ 83. The Specification’s Example 9 (¶ 84) shows a similar
experiment with Candida albicans; the control again is saline.
However, neither of the experiments described in Examples 8 and 9 of
the Specification shows any “therapeutic” effect, because both experiments
were conducted in vitro, and neither experiment shows a comparison to the
closest prior art: Leshchiner’s PVP-I/cortisone composition.
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The Specification’s Example 10 (¶¶ 85–8914) does describe the effect
of a PVP-I/budesonide composition on human subjects, but does not
compare that composition to any other treatment. In particular, the
PVP-I/budesonide composition is not compared to the closest prior art:
Leshchiner’s PVP-I/cortisone composition.
In summary, none of Appellants’ evidence of unexpected results
shows a comparison to the closest prior art, and therefore does not
persuasively show that the claimed invention is nonobvious over Leshchiner
and Cagle.
Furthermore, all of the cited experiments were conducted using
budesonide; none of them show results for the combination of PVP-I with
fluticasone, which is also encompassed by claim 1. “Evidence of unexpected
results must be reasonably commensurate with the scope of the claims.” In re
Huai-Hung Kao, 639 F.3d 1057, 1068 (Fed. Cir. 2011). “If an applicant . . .
provides an adequate basis to support the conclusion that other embodiments
falling within the claim will behave in the same manner [as a tested
embodiment], this will generally establish that the evidence is commensurate
with [the] scope of the claims.” Id.
Here, the evidence shows that dexamethasone sodium phosphate is
less storage-stable than budesonide. Liang Decl. ¶¶ 9–10. Appellants have
not provided any evidence of fluticasone’s storage stability. The evidence of
record thus does not show whether fluticasone is similar to budesonide with
respect to storage stability, or whether instead it is more similar to

14 Although Appellants cite “Paragraphs [0081]–[0098],” Br. 8, the
Specification has only ninety paragraphs.
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dexamethasone sodium phosphate. The evidence of record also does not
show that fluticasone is similar to budesonide with respect to solubility or
therapeutic effect. Thus, Appellants have not shown that the proffered
evidence of unexpected results is commensurate in scope with the claims.
For the reasons discussed above, we affirm the rejection of claim 1
under 35 U.S.C. § 103(a) based on Leshchiner and Cagle. Claims 2–5, 7–14,
and 23 were not argued separately and therefore fall with claim 1. 37 C.F.R.
§ 41.37(c)(1)(iv).
III
The Examiner has rejected claim 15 as obvious based on Leshchiner,
Cagle, and Haslwanter. The Examiner has rejected claims 19–21 as obvious
based on Leshchiner, Cagle, and Lulla. Appellants have waived arguments
directed to the additional teachings of Haslwanter or Lulla. See Br. 10–11.
We therefore affirm the rejections under 35 U.S.C. § 103(a) of claims 15 and
19–21 for the reasons set out in the Final Action and as discussed above.
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