Ex Parte Yang et al

Patent Trial and Appeal Board

Jan 12, 2015

11840537 (P.T.A.B. Jan. 12, 2015)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte ZHIJUN YANG, WENHUA HUANG,
CHI SUN WONG, and ZHONGZHEN ZHAO1
__________

Appeal 2012-006361
Application 11/840,537
Technology Center 1600
__________

Before ERIC B. GRIMES, MELANIE L. McCOLLUM, and ROBERT A.
POLLOCK, Administrative Patent Judges.

McCOLLUM, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a
pharmaceutical composition. The Examiner has rejected the claims as
anticipated or obvious. We have jurisdiction under 35 U.S.C. § 6(b). We
affirm.
STATEMENT OF THE CASE
Claims 1–5 and 17–22 are on appeal (App. Br. 4). Claim 1 is
representative and reads as follows:

1 Appellants identify the real party in interest as Hong Kong Baptist
University (App. Br. 2).
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1. An inhalable controlled release pharmaceutical dehydrated lipid
vesicle aerosolizable particle composition for treatment of asthma by
inhalation into a respiratory system, said composition comprising dehydrated
lipid vesicles having a non-aqueous pharmaceutically acceptable lipid
component and an active pharmaceutical ingredient without an inner water
phase encapsulated within the dehydrated lipid vesicles, the dehydrated lipid
vesicles including a pharmaceutically acceptable vesicle preserver including
at least one plasticizer and at least one stabilizer in an amount sufficient for
imparting flexibility to the dehydrated lipid vesicles and for acting as a
temporary barrier against efflux of the active pharmaceutical ingredient from
the lipid vesicle, the aerosolized particles being predominantly on the order
of smaller than 10 microns mass median aerodynamic diameter and large
enough to deposit on mucosal or respiratory system tissue to delay release of
the active pharmaceutical ingredient onto said mucosal or respiratory system
tissue, the controlled release of the active pharmaceutical ingredient being a
slow release of from 0% to 100% of the active pharmaceutical ingredient in
a period of up to 72 hours after inhalation such that a minimal dosing of said
active pharmaceutical ingredient is used to produce maximal effect extended
over a period of time by a controlled release mechanism.
(Amendment filed June 3, 2011.)2
Claims 1–3 and 17–21 stand rejected under 35 U.S.C. § 102(b) as
anticipated by Lenk3 (Ans. 7).
Claims 5 and 17–21 stand rejected under 35 U.S.C. § 103(a) as
obvious over Lenk (Ans. 11).
Claim 4 stands rejected under 35 U.S.C. § 103(a) as obvious over
Lenk in view of Harwigsson4 (Ans. 13).

2 We note that claim 1 as set forth in the Claims Appendix to the Appeal
Brief differs from claim 1 as set forth in the Amendment filed June 3, 2011
(the most recent amendment of the claims). We are basing our decision on
the claim as set forth in the Amendment filed June 3, 2011.
3 Lenk et al., US 5,262,168, Nov. 16, 1993.
4 Harwigsson, WO 2004/054556 A1, July 1, 2004.
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Claim 4 stands rejected under 35 U.S.C. § 103(a) as obvious over
Lenk in view of Harwigsson, Powell,5 and Rosenthal6 (Ans. 15).
Claim 22 stands rejected under 35 U.S.C. § 103(a) as obvious over
Lenk in view of Schmidt7 (Ans. 18).
I
The Examiner finds:
“[Lenk] discloses a liposome composition which
comprises an arachidonic acid metabolite which is preferably a
prostaglandin, a lipid, a drying protectant, and a partition-
enhancing buffer or buffering system...[t]he partitioning
enhancing buffer system comprises...a saccharide solution,
and...a citric acid solution. The saccharide solution is
preferably...dextrose, sucrose, or maltose...The liposome
solution can then be size reduced by, for example, an extrusion
of homogenization procedure. The resulting solution can be
dried by a dehydration or a lyophilization procedure” . . . .
According to instant claim 3 , the instant application defines
citric acid as a stabilizer. According to instant claim 2, the
instant application defines white soft sugar as a plasticizer.
White soft sugar is a saccharide also known in the art as
sucrose. . . .
Furthermore, . . . “[Lenk] discloses an encapsulation
procedure which significantly improves both the partitioning
and subsequence entrapment of the prostaglandin into the
liposome, and the stability of the liposome-entrapped
prostaglandin formulation” . . . .

5 C. E. Powell et al., The Pharmacological Action of 1-o-Chlorophenyl-2-
Isopropylaminoethanol (Isoprophenamine); A Bronchodilator, 45 J. AM.
PHARM. ASSOC. 785–787 (1956).
6 Rosenthal et al., US 2002/0119104 A1, Aug. 29, 2002.
7 Schmidt et al., US 5,817,334, Oct. 6, 1998.
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Lenk . . . teach[es] that their prostaglandin-liposomal
formulations are between 100-500nm . . . and “prostaglandin-
liposome product...sterile filtered through a 0.2 µm filter...dried
(dehydrated)” . . . . Based upon Lenk’s teachings, their
particles are clearly “large enough to deposit on the lung.”
(Ans. 8–9.)
Analysis
Appellants argue that “Lenk’s liposome does not encapsulate the
pharmaceutical and does not have a plasticizer or a stabilizer as part of the
liposome as required by the present claims” (App. Br. 9). We are not
persuaded.
As noted by the Examiner (Ans. 8–9), Lenk “discloses an
encapsulation procedure which significantly improves both the partitioning
and subsequent entrapment of the prostaglandin into the liposome, and the
stability of the liposome-entrapped prostaglandin formulation” (Lenk, col. 3,
ll. 30–34). In addition, Lenk discloses that the liposome composition
comprises a “partition-enhancing buffer system compris[ing] two solutions,
one being a solution of a drying protectant, preferably a saccharide solution,
and the second, preferably a citric acid solution,” wherein the “saccharide
solution is preferably dextrose, sucrose, or maltose, any of which may be
combined with mannitol” (id. at col. 4, ll. 7–20). The Examiner finds that
citric acid is a stabilizer and that sucrose is a plasticizer (Ans. 8). Appellants
have not adequately explained why these teachings fail to describe a lipid
vesicle encapsulating an active pharmaceutical ingredient and including a
plasticizer and a stabilizer.
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Appellants also argue that Lenk “fails to teach or suggest that their
liposome composition can be administered in a dehydrated form or via
inhalation” (App. Br. 10). We are not persuaded.
As noted by the Examiner (Ans. 8), Lenk discloses that its “solution
can be dried by a dehydration or a lyophilization procedure” (Lenk, col. 4,
ll. 29–30). Given that claim 1 is directed to a product, we agree with the
Examiner that Lenk need not disclose that its composition “can be
administered in a dehydrated form or via inhalation” (Ans. 23). Appellants
have not adequately explained why Lenk’s dehydrated product is not
capable of being administered by inhalation.
In addition, Appellants argue that Lenk “fails to teach or suggest
aerosolizable particles that include dehydrated lipid vesicles. Those
ordinary skilled in the art understand that such compositions necessarily
include ingredients that facilitate aerosolization as described throughout the
present specification.” (App. Br. 10.) We are not persuaded.
“[D]uring examination proceedings, claims are given their broadest
reasonable interpretation consistent with the specification.” In re Hyatt, 211
F.3d 1367, 1372 (Fed. Cir. 2000). We note initially that Appellants fail to
state with any particularity where the Specification indicates that the
“compositions necessarily include ingredients that facilitate aerosolization”
(App. Br. 10). However, even if aerosol compositions necessarily include
ingredients that facilitate aerosolization, claim 1 merely recites a
“dehydrated lipid vesicle aerosolizable particle composition.” We conclude
that Appellants have not adequately explained why it is unreasonable for the
Examiner to interpret this language to merely require a composition
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comprising dehydrated lipid vesicle particles that are capable of being
aerosolized (Ans. 4–5). In addition, Appellants have not adequately
explained why Lenk’s dehydrated product is not capable of being
aerosolized.
Appellants also argue that “the reduced rate of release[] described by
Lenk is totally different from the controlled release of pharmaceuticals over
an extended period by the liposomes of the subject claims which deposit on
the respiratory tissue” (App. Br. 10 (emphasis omitted)). We are not
persuaded.
Claim 1 recites:
the controlled release of the active pharmaceutical ingredient
being a slow release of from 0% to 100% of the active
pharmaceutical ingredient in a period of up to 72 hours after
inhalation such that a minimal dosing of said active
pharmaceutical ingredient is used to produce maximal effect
extended over a period of time by a controlled release
mechanism.
However, given that Appellants have not adequately explained how the
claimed composition differs structurally from Lenk’s composition, we agree
with the Examiner that Appellants have not adequately explained why
Lenk’s composition would not have the claimed controlled release property
(Ans. 22–23). “[I]t is elementary that the mere recitation of a newly
discovered function or property, inherently possessed by things in the prior
art, does not cause a claim drawn to those things to distinguish over the prior
art.” In re Swinehart, 439 F.2d 210, 212–13 (CCPA 1971).
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Conclusion
The evidence supports the Examiner’s conclusion that Lenk
anticipates claim 1. We therefore affirm the anticipation rejection of
claim 1. Claims 2, 3, and 17–21 have not been separately argued and
therefore fall with claim 1. 37 C.F.R. § 41.37(c)(1)(vii).
II
With regard to the obviousness rejection over Lenk, we select
claim 21 as representative. Claim 21 depends from claim 1 and recites that
“the composition has a ratio of said vesicle preserver to said lipid component
from 0.1 to 40 mole % of the vesicle preserver and from 99.9 to 60 mole %
of the lipid component” (App. Br. 22).
The Examiner finds that Lenk teaches “that the weight ratio of lipid to
prostaglandin is about 150:1 to about 1000:1 in a citric acid buffer” and “that
their composition can comprise about 5% to 20% by weight of saccharide”
(Ans. 12). The Examiner concludes that Lenk teaches “embodiments which
are encompassed by or overlap instant claim 21” (id.).
Analysis
Appellants argue that, “for the reasons put forth above, it is
respectfully submitted that claim[] . . . 21 cannot be obvious in view of Lenk
et al as nowhere in Lenk et al. teaches or suggests the inhalable dehydrated
lipid vesicles composition of claim[] . . . 21” (App. Br. 11). We are not
persuaded for the reasons discussed above.
Conclusion
The evidence supports the Examiner’s conclusion that Lenk renders
claim 21 obvious. We therefore affirm the obviousness rejection of
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claim 21. Claims 5 and 17–20 have not been separately argued and
therefore fall with claim 21. 37 C.F.R. § 41.37(c)(1)(vii).
III
Claim 4 depends from claim 1 and recites that the active
pharmaceutical ingredient is selected from a group that includes albuterol
(App. Br. 16). In rejecting this claim, the Examiner relies on Lenk as
described above (Ans. 13). However, the Examiner finds that Lenk does
“not teach lyophilized-liposomal preparations of the pharmaceutically active
ingredients listed in claim 4” (id.).
The Examiner relies on Harwigsson for teaching “a pharmaceutical,
preferably inhalable, particle comprising a therapeutically active compound
and lipids,” “that the particles are evaporated to dryness,” that its “‘invention
can comprise...optional excipients...stabilizers such as citric acid’ . . . ,
thereby suggesting the particular plasticizer and stabilizer, citric acid,” and
“that these compositions are dried into a powder” (id.). The Examiner also
finds that “Harwigsson teach[es] that prostaglandins . . . and broncho-
dilators, such as albuterol . . . can be formulated into pharmaceutical,
preferably inhalable, particles comprising a therapeutically active compound
and lipids” (id. at 13–14). The Examiner concludes that it would have been
obvious “to provide a composition comprising dehydrated lipid vesicles of
pharmaceutically acceptable vesicle preserver (sodium citrate),
pharmaceutically acceptable lipid component and active pharmaceutical
ingredient (albuterol)” (id. at 14).
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Analysis
Appellants argue:
Harwigsson merely discloses lipid particles in which a
pharmaceutical material is bound to a three dimensional lipid
structure agglomerate . . . , rather than encapsulated within a
dehydrated lipid vesicle as required by the claims on appeal.
More specifically, Harwigsson describes that water content is
critical in formulating the three dimensional lipid particle
structure thereof . . . . There is no implication that a dehydrated
liposome that encapsulates pharmaceutical ingredient is taught
anywhere in Harwigsson.
(App. Br. 11.) We are not persuaded.
As discussed above, Lenk discloses that its “solution can be dried by a
dehydration or a lyophilization procedure” (Lenk, col. 4, ll. 29–30).
Similarly, Harwigsson discloses that “particles compatible with the instant
invention may be formed by, techniques including, but not limited to, spray
drying, vacuum drying, freeze drying, extrusion, or other suitable techniques
and combinations thereof” (Harwigsson 16: 15–17).
As also discussed above, Lenk “discloses an encapsulation procedure
which significantly improves both the partitioning and subsequent
entrapment of the prostaglandin into the liposome, and the stability of the
liposome-entrapped prostaglandin formulation” (Lenk, col. 3, ll. 30–34).
The Examiner does not rely on Harwigsson for specifically teaching
encapsulation (Ans. 13–15 & 25). Instead, the Examiner concludes that it
would have been obvious to substitute albuterol, as disclosed in Harwigsson,
for the prostaglandin in Lenk’s vesicles (id.).
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Appellants also argue:
[E]ven if one skilled in the art were to replace prostaglandin in
the liposome composition of Lenk et al. with albuterol in light
of Harwigsson, it is not seen that the combination of the two
cited references would lead one skilled in the art to arrive [at]
the inhalable dehydrated lipid vesicle composition of the
present application.
(App. Br. 11–12.) We are not persuaded for reasons discussed above.
Conclusion
The evidence supports the Examiner’s conclusion that Lenk and
Harwigsson render claim 4 obvious. We therefore affirm the obviousness
rejection of claim 4 over Lenk and Harwigsson.
IV
In the second rejection of claim 4, the Examiner notes that Appellants
have “elected a species of composition for examination which comprises
citric acid (stabilizer/plasticizer) and clorprenaline glycyrrhizinate
(pharmaceutically active ingredient)” (Ans. 15).
In rejecting claim 4 on this basis, the Examiner relies on Lenk and
Harwigsson as described above (id.). The Examiner also finds:
“Isoprophenamine (Clorprenaline) is a bronchodilator . . . . While,
Harwigsson does not teach the specific species of bronchodilator,
clorprenaline, Harwigsson does teach that the active pharmaceutical agents
can be of the genus, bronchodilators.” (Id. at 16.)
The Examiner relies on Powell for teaching “delivery of the specific
bronchodilator active agent, isoprophenamine hydrochloride (i.e.,
clorprenaline hydrochloride)” (id. at 16–17). However, the Examiner finds
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that “Lenk in view of Harwigsson in view of Powell . . . do not teach
clorprenaline glycyrrhizinate” (id. at 17).
The Examiner relies on Rosenthal for teaching “that glycyrrhizinate
salts act as penetration enhancers when delivered with therapeutic agents to
mucosal endothelium” (id.). The Examiner concludes that “a skilled artisan
would be motivated to use clorprenaline glycyrrhizinate over other salts of
clorprenaline, since it would enhance the delivery of clorprenaline
(isoprophenamine) to lung mucosa” (id.).
Analysis
Appellants argue that neither Powell8 nor Rosenthal
relates to pharmaceutical ingredients encapsulated in lipid
vesicle compositions, let alone a dehydrated lipid vesicle
composition as required by the claims on appeal. Accordingly,
one skilled in the art would not be motivated to combine the
teachings of [Powell] and Rosenthal with Harwig[s]son and
Lenk, as a skilled artisan would not reasonably expect the
pharmaceutical ingredients of a non-lipid composition would be
applicable to a lipid-containing composition.
(App. Br. 12.) We are not persuaded.
As noted by the Examiner (Ans. 13), Harwigsson “relates to a
pharmaceutical, preferably inhalable, porous, free flowing particle to be used
in therapeutical applications, optionally comprising a therapeutically active
compound or substance, [such as prostaglandins,] whereby the particle
consists of one or more network forming compounds, which in diluted
solutions self associate[] to large three dimensional structures” (Harwigsson,

8 As noted by the Examiner, Powell was previously referred to as Gibson
(Ans. 4).
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Abstract & 18: 10). As noted above, Harwigsson discloses that “particles
compatible with the instant invention may be formed by, techniques
including, but not limited to, spray drying, vacuum drying, freeze drying,
extrusion, or other suitable techniques and combinations thereof” (id. at 16:
15–17). In addition, Harwigsson discloses that lipids “may be used in
varying concentration to form suitable structures” (id. at 12: 10–12).
Harwigsson also discloses “that other component(s) can be included,” such
as stabilizers, buffers, and sugars (id. at 25: 11–19). In particular,
Harwigsson discloses “buffer substances or stabilizers such as citric acid”
and carbohydrates such as sucrose (id. at 25: 24–32).
In addition, Harwigsson discloses that the “physiologically active
agent which can be used in the present invention includes . . . broncho-
dilators” (id. at 17: 1–3). Powell discloses that isoprophenamine, which the
Examiner indicates is also known as clorprenaline (Ans. 16), is a
bronchodilator (Powell 785). Rosenthal identifies glycyrrhizinate salts as
penetration enhancers (Rosenthal ¶ 58). Thus, we conclude that the
Examiner has set forth a prima facie case that it would have been obvious to
include clorprenaline, specifically clorprenaline glycyrrhizinate, in the lipid
compositions of Harwigsson and Lenk (Ans. 15–18).
Appellants also argue that “even if combined, the combination would
not teach or suggest the inhalable dehydrated lipid vesicle composition of
the present claims” (App. Br. 12). We are not persuaded for reasons
discussed above.
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Conclusion
The evidence supports the Examiner’s conclusion that Lenk,
Harwigsson, Powell, and Rosenthal render claim 4 obvious. We therefore
affirm the obviousness rejection of claim 4 over Lenk, Harwigsson, Powell,
and Rosenthal.
V
Claim 22 ultimately depends from claim 1 and recites that “the
plasticizer is selected from glycerin or its derivatives” (App. Br. 22). In
rejecting this claim, the Examiner relies on Lenk as described above
(Ans. 18). However, the Examiner finds that Lenk does “not teach
lyophilized-liposomal preparations comprising the particular plasticizer,
glycerin (i.e., glycerol)” (id. at 19).
The Examiner relies on Schmidt for teaching that “breakage of the
liposomes during drying is common when cryoprotectants are not used”
(id.). The Examiner finds that Schmidt teaches “a variety of potential
cryoprotectants, including dextrose, sucrose and glycerol (glycerin)” (id.).
The Examiner concludes that it would have been obvious “to provide a
composition comprising dehydrated lipid vesicles of pharmaceutically
acceptable vesicle preserver (citric acid), plasticizer (glycerin),
pharmaceutically acceptable lipid component and active pharmaceutical
ingredient (prostaglandin)” (id.).
Analysis
Appellants argue: Schmidt “does not cure the deficiencies of Lenk et
al. Specifically, Schmidt et al. does not teach or suggest a dehydrated lipid
vesicle composition. Instead, Schmidt requires reconstitution of dried
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stabilized liposomes which encapsulate active ingredient with an inner water
phase.” (App. Br. 12–13.)
However, Schmidt is merely being relied on to teach glycerin
(Ans. 19). Thus, we are not persuaded by the argument that Schmidt does
not overcome other alleged deficiencies in Lenk for reasons discussed
above.
Conclusion
The evidence supports the Examiner’s conclusion that Lenk and
Schmidt render claim 22 obvious. We therefore affirm the obviousness
rejection of claim 22.
SUMMARY
We affirm the anticipation rejection of claims 1–3 and 17–21 over
Lenk, the obviousness rejection of claims 5 and 17–21 over Lenk, the
obviousness rejections of claim 4 over Lenk in view of Harwigsson and over
Lenk in view of Harwigsson, Powell, and Rosenthal, and the obviousness
rejection of claim 22 over Lenk in view of Schmidt.
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

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