Ex Parte Schutt et al

Patent Trial and Appeal Board

Aug 18, 2017

13083485 (P.T.A.B. Aug. 18, 2017)

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.
13/083,485 04/08/2011 ERNEST GEORGE SCHUTT PCIRA.034A 8263
20995 7590 08/22/2017
KNOBBE MARTENS OLSON & BEAR LLP
2040 MAIN STREET
FOURTEENTH FLOOR
IRVINE, CA 92614
EXAMINER
KISHORE, GOLLAMUDI S
ART UNIT PAPER NUMBER
1612
NOTIFICATION DATE DELIVERY MODE
08/22/2017 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):
jayna.cartee@knobbe.com
efiling @ knobbe. com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte ERNEST GEORGE SCHUTT, RONALD WARREN McGUIRE,
PETER ANDREW WALTERS, and KATHLEEN D.A. LOS
Appeal 2017-0035831
Application 13/083,485
Technology Center 1600
Before RICHARD M. LEBOVITZ, JOHN E. SCHNEIDER, and
RYAN H. FLAX, Administrative Patent Judges.
LEBOVITZ, Administrative Patent Judge.
DECISION ON APPEAL
This appeal involves claims directed to multivesicular liposome
droplets. The Examiner rejected the claims under 35 U.S.C. §§ 102, 103,
and § 112. We have jurisdiction under 35 U.S.C. § 6(b). The §§ 102 and
103 rejections are affirmed, but are designated a new ground of rejection
pursuant to 37 C.F.R. § 41.50(b). A new § 103 rejection is also set forth
pursuant 37 C.F.R. § 41.50(b). The rejection under 35 U.S.C. § 112, second
paragraph, is reversed.
1 The Appeal Brief (“Appeal Br.”) 3 lists Pacira Pharmaceuticals Inc. as the
real-party-in-interest.
Appeal 2017-003583
Application 13/083,485
STATEMENT OF CASE
The claims stand rejected by the Examiner as follows:
1. Claims 28, 105, 107—112, 153, 154, 156, and 157 under pre-AIA
35 U.S.C. § 102(b) as anticipated by Hartounian (US Publ. Pat. App.
2007/0235889 Al, publ. Oct. 11, 2007). Ans. 3.
2. Claims 28, 105, 107—113, 153, 154, and 156—158 under pre-
AIA 35 U.S.C. § 103(a) as obvious in view Hartounian or Sankaram (US
5,766,627, iss. June 16, 1998) or Kim ’017 (US 5,576,017, iss. Nov. 19,
1996), or Kim ’835 (US 8,182,835 B2, iss. May 22, 2012), individually or in
combination (collectively, “the MLV references”), and further in view of
Yuzhakov (US Publ. Pat. App. 2009/0017108 Al, publ. Jan. 15, 2009).2
Ans. 3^4.
3. Claims 113 and 158 under pre-AIA 35 U.S.C. § 103(a) as obvious
in view Hartounian or Sankaram or Kim ’017 or Kim ’835, individually or
in combination, and further in view of Yuzhakov and Bolotin (US
6,162,462, publ. Dec. 19, 2000). Ans. 5.
4. Claims 28, 105, 107—113, 153—154 and 156—158 are rejected under
35 U.S.C. § 112(b) or 35 U.S.C. § 112 (pre-AIA), second paragraph, as
indefinite. Ans. 2.
There are two independent claims on appeal, claims 28 and 105.
Claim 28 is selected as representative of the rejected subject matter and
reads as follows:
2 The Examiner stated “or in further combination” with Yuzhakov. Ans. 5.
It is not clear whether the Examiner intended the MLV references to be
stated in the alternative and then Yuzhakov for its teaching of liposomal
sizes, but not in the alternative. We have written the rejection in the way it
appears to have been intended.
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28. Atomized droplets, each droplet comprising:
a core, wherein the core comprises:
i) aqueous phase droplets, wherein the aqueous phase
droplets have an average diameter of from 10 nm to 10 pm,
ii) an organic phase comprising an organic solvent,
wherein the organic solvent is a volatile water-immiscible or
sparingly miscible solvent and the aqueous phase droplets are
suspended in the organic solvent,
iii) at least one amphipathic lipid, and
iv) at least one glycerol ester; and an aqueous phase shell
contacting the organic solvent of the core, wherein the aqueous
phase droplets do not contact the aqueous phase shell,
wherein the atomized droplets have an average diameter
from about 10 pm to about 100 pm, and wherein each atomized
droplet is individually surrounded by a continuous gas phase.
1. ANTICIPATION REJECTION
FF1,3 Claim 28 is directed to an atomized droplet comprising: a core
(A) and an aqueous phase shell (B). The core comprises an organic phase
(ii). The atomized droplet is therefore an oil-in-water emulsion because the
organic phase (ii) (the oil) is present in and surrounded by the aqueous shell
(B) (the water).
FF2. The core (A) comprises aqueous phrase droplets (i), which are
suspended in the claimed organic phase (ii). The core is therefore a water-
in-oil emulsion because the aqueous phrase droplets (i) (the water) are
suspended in the organic phase (ii) (the oil).
FF3. The core (A) also contains at least one amphipathic lipid (iii)
and at least one glycerol ester (iv). The core (A) of the droplet can further
comprise a therapeutic agent (claim 157).
3 “jrp” refers to Findings of Fact.
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FF4. The Specification characterizes the atomized droplet as a
“multivesicular liposome” or “MLV.” Spec. 12.
FF5. Fig. 9A of the Specification, annotated herein, shows the same
structure which is recited in the claim:
X,
X
aqueoiss
904
FIG. 9A
8'Si
Fig. 9A shows core (A) containing aqueous phase droplets (i) and an
organic solvent (ii); and also shows an aqueous phase shell (B), altogether
providing the multivesicular liposome 902.
FF6. Claim 28 further requires that each atomized droplet “have an
average diameter from about 10 pm to about 100 pm” and “is individually
surrounded by a continuous gas phase.”
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FF7. The Specification explains that the continuous gas phase, as
recited in claim 28, is used to remove solvent and distinguishes such a
method from sparging, as follows:
It was surprisingly discovered that forming a first
emulsion surrounded by an aqueous shell [(B)] in the form of a
droplet and contacting it with a continuous gas phase, reduces
the time needed to remove the organic solvent to a few seconds
and possibly a fraction of a second, (much less than the tens of
minutes stated above for batch processing).
This is due to the tremendous gas contacting surface area
of the atomized droplets; and the much faster diffusion of the
solvent in gasses versus water; and the very short distances that
the solvent has to diffuse through the aqueous phase to reach
the gas (now only microns instead of the distanced between
sparging bubbles.)
Spec. 1179-80.
Hartounian
Hartounian describes several steps to produce an MVL, which the
Examiner found anticipated the claimed atomized droplets. The steps of
Hartounian cited by the Examiner, and how they result in the claimed
atomized droplets, are explained in the findings of fact below. Examples 1
and 2 of Hartounian have similar disclosure and were cited by the Examiner,
as well.
FF8.
In one aspect, the invention provides a process for producing
MVL by providing a water in oil (w/o) emulsion, which is
made from an aqueous phase dispersed in a solvent phase
containing amphipathic and neutral lipids.
Hartounian 117.
FF9.
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Production of multivesicular liposomes (MVL) requires several
process steps. An example of lab-scale production is set forth
in Sankaram et al., U.S. Pat. No. 5,766,627, incorporated herein
by reference. Briefly, the method for making MVL at the
laboratory scale is as follows: a water-in-oil (w/o) emulsion is
prepared by capturing in a lipid component composed of at
least one amphipathic lipid and at least one neutral lipid in one
or more volatile water-immiscible solvents for the lipid
component, an immiscible first aqueous component optionally
and preferably containing a biologically active substance to be
encapsulated. . .
Id. at | 61. See also id. 1 68 (discussion of making the first w/o emulsion.
FF10. The first process step in Hartounian of making a w/o emulsion,
containing an amphipathic lipid and a neutral lipid (FF8, FF9) meets the
limitation of claim 28 of the w/o core (FF2) having at least one amphipathic
lipid (iii) and at least one glycerol ester (iv) (FF3).
FF11. The glycerol ester (iv) of claim 28 is a neutral lipid. Spec, at p.
3,1. 15-16.
FF12. After making the first w/o emulsion, Hartounian teaches:
FF13. The first “w/o emulsion is dispersed into another aqueous
phase to make water-in-oil-in-water (w/o/w) emulsion.” Hartounian 119.
FF14. “The mixture is emulsified [of FF8, FF9], and then mixed with
a second immiscible aqueous component to form a water-in-oil-in-water
(w/o/w) second emulsion.” Id. at 161.
FF15. “The first emulsion is then mixed with a second aqueous
solution, and emulsified to form a w/o/w emulsion comprising solvent
spherules suspended in the second aqueous component.” Id. at | 88.
FF16. The second process step described in Hartounian of mixing the
w/o emulsion of FF8 and FF9 with a second aqueous solution (FF13—FF15)
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results in the limitation of claim 28 of the core (A) (w/o emulsion)
surrounded by an aqueous phase shell (B) (FF1).
Continuous gas phase disclosure in Hartounian
FF17.
The mixture is emulsified, and then mixed with a second
immiscible aqueous component to form a water-in-oil-in-water
(w/o/w) second emulsion. The turbulence required for
formation of the second emulsion is provided either
mechanically (for example by rotor/stator, homogenizer, or
other high-shear mixer), by ultrasonic energy, nozzle
atomization, and the like, or by combinations thereof, to form
solvent spherules suspended in the second aqueous component.
Hartounian 161.
Size disclosure in Hartounian
FF18. Claim 28 requires that the aqueous phase droplets (i) have an
average diameter of from 10 nm to 10 pm. These droplets are surrounded by
the organic phase solvent (ii).
FF19. Claim 28 also requires that the atomized droplets have an
average diameter from about 10 pm to about 100 pm,
The Examiner found these sizes described in Hartounian.
FF20. In the section titled “First Emulsion,” Hartounian teaches:
The droplet size in the first emulsion will vary depending on,
energy input, the components used, the volume fraction of
aqueous and organic solutions, and the desired stability and
release profiles, but in general will be in the range of about 0.05
[50 nm] to about 3 pm, preferably from about 0.1 to about 1 82
m [sic]. Droplet size can be determined directly (for example,
microscopically), or indirectly, for example based on mixing
time, or mixture viscosity. Different droplet sizes are obtained
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by varying the emulsification method (for example, by
adjusting the impeller speed in the case of mechanical
emulsification) and temperature.
Id. at | 87.
FF21. The range of about 50 nm to about 3 pm described in
Hartounian (FF20) falls within the claimed range of from 10 nm to 10 pm,
anticipating it.
FF22. For the second w/o/w emulsion, Hartounian describes a
particle sizes of: “Particles generated under these conditions were 10 to 12
pm. The particle size specification for this product is 13 to 18 pm.” Id. at |
150.
FF23. The range of 13 to 18 pm described in Hartounian (FF22) falls
within the claimed range of about 10 pm to about 100 pm, anticipating it.
Arguments
Sizes
While the Examiner made certain statements about inherency with
regard to the droplet size of the first emulsion, the Examiner also made
express findings of the specific ranges described by Hartounian which fall
within the scope of the claimed ranges, including referencing paragraph 87
of Hartounian (FF20). Final Act. 5. Thus, we find Appellants’ arguments
about inherency to be moot. Appeal Br. 13—14.
Appellants contend:
Hartounian merely discloses the size of the first emulsion (i.e.,
water-in-oil emulsion) having a diameter in the range from
about 0.05 to about 3 pm. The claimed aqueous phase droplets
correspond to the “water” portion of the first emulsion of
Hartounian, not the first emulsion itself.
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Appeal Br. 15.
This argument does not persuade us that the Examiner erred. As
argued by the Examiner, “the aqueous phase droplets are suspended in the
organic solvent which implies organic solvent is the continuous phase in
which the aqueous droplets are suspended. Ans. 6. In other words, the only
droplets present in the first emulsion are the aqueous droplets. FF20.
Appellants have not provide sufficient evidence on this record to distinguish
the claimed droplet size from the disclosed droplet size of Hartounian (FF20,
FF21).
As to the second recited size of the particles, Appellants argue that
Examiner did not provide adequate fact or technical reasoning as to why
emulsions produced by different processes would provide the same size
droplets. Appeal Br. 15. However, as indicated above, the Examiner cited
specific sizes of both the droplets (i) and atomized droplets (FF22, FF23)
which anticipate the claimed subject matter and the Examiner did not solely
rely on inherency arguments.
Gas
Claim 28 further requires that each droplet “is individually surrounded
by a continuous gas phase.” FF6. According to Appellants, a device with an
atomizing nozzle is used to make the atomized droplets surrounded by a
continuous phase gas. Appeal Br. 5—6. Hartounian discloses making the
second emulsion utilizing “nozzle atomization.” FF17. Because nozzle
atomization is utilized in both Hartounian and the claimed subject matter, it
is reasonable to conclude that the nozzle atomization in Hartounian would
result in atomized droplets individually surrounded by a continuous gas
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phase in the same way as described in the Specification and as required by
the claims.
As held in In re Best, 562 F.2d 1252, 1255 (CCPA 1977):
Where, as here, the claimed and prior art products are identical
or substantially identical, or are produced by identical or
substantially identical processes, the PTO can require an
applicant to prove that the prior art products do not necessarily
or inherently possess the characteristics of his claimed product.
Whether the rejection is based on “inherency” under 35 U.S.C.
§ 102, on “prima facie obviousness” under 35 U.S.C. § 103,
jointly or alternatively, the burden of proof is the same, and its
fairness is evidenced by the PTO’s inability to manufacture
products or to obtain and compare prior art products.
Once “the PTO shows sound basis for believing that the products of
the applicant and the prior art are the same, the applicant has the burden of
showing that they are not.” In re Spada, 911 F.2d 705, 708 (Fed. Cir. 1990).
The Examiner did not rely on Hartounian’s disclosure of “nozzle
atomization” to meet the continuous gas phase limitation. Thus, because our
reasoning and fact-finding is different from the Examiner’s (See In re
Stepan, 660 F.3d. 1341, 1344-45 (Fed. Cir. 2011)), we designate this as a
new ground of rejection pursuant to 37 C.F.R. § 41.50(b). The new ground
is under 35 U.S.C. § 102(b), which is the same statutory ground as the
Examiner’s rejection.
Summary
For the foregoing reasons, the anticipation rejection of claim 28 is
affirmed. Claim 105 has similar limitations as claim 28 and the rejection of
it is affirmed for the same reasons. The rejection of dependent claims 107—
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112, 153, 154, 156, and 157 is affirmed for the reasons set forth by the
Examiner. Final Act. 7—8. Appellants did not provide separate arguments
for these claims (Appeal Br. 17) and thus these claims fall with the
independent claims. 37 C.F.R. § 41.37(c)(l)(iv). These affirmances are
designated as a new ground of rejection,
2. OBVIOUSNESS REJECTION BASED ON MLV METHODS
The obviousness rejection adds additional publications which describe
MLV production utilizing methods similar to Hartounian, including nozzle
atomization (see, e.g., Sankaram, col. 4,11. 36—37. We found all the
limitations of the claims are met by Hartounian and thus, for the same
reasons, affirm the obviousness rejection based on the additional MLV
publications. We also designate this as a new grounds of rejection because
the reasoning and fact-finding based on Hartounian differs from the
Examiner’s.
3. OBVIOUSNESS REJECTION BASED ON BOLOTIN
The Examiner further cited Bolotin for its teaching of the therapeutic
agent recited in claims 113 and 158. Final Act. 10—11.
We have considered Appellants’ arguments as to why the rejection is
deficient, but do not find them persuasive. Appellants attempted to
distinguish the claims based on the different methods used in Bolotin as
compared to Hartounian and the additional cited MLV publications. Appeal
Br. 19. However, the Examiner only relied upon Bolotin for its teaching of
the therapeutic agent in liposomes. Ans. 11. Consequently, we conclude
that Appellants have not identified an error in the rejection and affirm the
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rejection based on Bolotin for the reasons set forth by the Examiner. We
also designate this as a new grounds of rejection because the underlying
reasoning for the rejection, which is based on Hartounian, differs from the
Examiner’s.
4. 112, SECOND PARAGRAPH, REJECTION
The Examiner rejected the claims as indefinite under § 112, second
paragraph. Final Act. 2. As explained in Findings of Facts 1—5, we found
the claims to clearly reflect the subject matter as claimed and as described in
the Specification, specifically as depicted in Fig. 9 A of the Specification.
We thus reverse the rejection.
The additional claimed requirement regarding presence of a
continuous gas phase is not depicted in Fig. 9A. However, because the
claimed droplets are formed by atomization, each droplet would necessarily
be surrounded by a continuous gas phase when a atomization nozzle is
utilized. A final product, where the solvent is removed by the atomization,
is not claimed.
To the extent that the Examiner expressed doubt that the claimed
atomized droplets can be obtained, we note that a rejection under 35 U.S.C.
§112, first paragraph, for lack of enablement under the proper interpretation
of claims 28 and 105 has not been made. See Ans. 6 (lines 16—18).
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5. NEW GROUNDS OF REJECTION BASED ON HARTOUNIAN,
REDZINIAK, AND HSU
We set forth the following new ground of rejection pursuant to 37
C.F.R. § 41.50(b) based on Hartounian, Redziniak,4 and Hsu.5
Claims 28 and 105 are rejected under 35 U.S.C. § 103 as obvious in
view of Hartounian, Redziniak, and Hsu. We leave it to the Examiner to
address the dependent claims and make additional findings of fact he
determines to be pertinent to the independent and dependent claims.
FF24. Redziniak teaches:
The method of the invention therefore comprising dissolving in
a solvent or a mixture of appropriate solvents the basic
constituents, in other words at least one amphiphilic lipid and
possibly one hydrophobic or partially hydrophobic constituent
desired to be incorporated into the lipidic bilayers.
The solution obtained is thereafter atomized. This operation
particularly comprises introducing the solution, in the form of
very fine droplets, e.g. by means of a spray nozzle or atomizer,
into an enclosed space traversed by a gaseous fluid heated to a
temperature higher than the boiling point of the solvent used.
The solvent is vaporized under the action of heat and is
entrained by the gaseous flow.
Redziniak col. 4,11. 22—35.
FF25. Hsu, in its Background section, describes various known
methods of making liposomes with a spray nozzle:
PCT Application WO 89/11850, published 14 December
1989, teaches a method for forming liposomes having an
additional material entrapped in the lipid bilayer, or in
association with a component of the bilayer, rather then [sic]
4 U.S. Pat. No. 4,508,703, iss. Apr. 2, 1985 (“Redziniak”).
5 WO 95/01164, publ. Jan. 12, 1995 (“Hsu”).
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having being entrapped inside the space created by a spherical
bilayer. This application teaches that aerosolization may be
used, by putting material into a sprayer or trigger pump such as
would be commonly used for applying non-pressurized hair
sprays, insecticides, and the like to other surfaces. According
to this application, upon spraying the formed solution (of lipid
and material), it is mixed with air and the volatile solvent
evaporates as the solution leaves the nozzle.
U.K. patent application GB 2,145,107A published 20
March 1985 teaches producing an aerosol spray containing
liposomes. The liposomes are produced by combining under
pressure an aqueous solution and a lipid mixture, and passing
the mixture, still under pressure, through a nozzle or other
arrangement to produce an aerosol spray containing liposomes.
Id. at Hsu at p. 2,1119-29.
FF26. Hsu teaches that its ultrasonic atomization can be performed
with an inert gas in the reservoir during the spraying process using an
atomizer nozzle. Id. atp. 19,11. 13—16; p. 1,11. 13—29.
Rejection
Hartounian is relied upon, as discussed above, for teaching the
claimed droplet with a core (A) and aqueous shell (B). Redziniak and Hsu
teach forming liposomes with a spray nozzle or atomizer, which would
result in each droplet being surrounded by a continuous gas phase either
from the ambient air (FF25), the inert gas introduced during the atomization
process (FF26), or when the emulsion is sprayed into the gas (FF24). It
would have been obvious to one of ordinary skill in the art to have used any
of these known spray atomization methods to make the liposomes of
Hartounian because Hartounian expressly suggests using nozzle atomization
(FF17) and it is obvious to utilize a method for its known function. As held
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in KSR Inti Co. v. Teleflex Inc., 550 U.S. 398, 417 (2007), “if a technique
has been used to improve one device, and a person of ordinary skill in the art
would recognize that it would improve similar devices in the same way,
using the technique is obvious unless its actual application is beyond his or
her skill.”
TIME PERIOD FOR RESPONSE
This Decision contains a new ground of rejection pursuant to
37 C.F.R. § 41.50(b). Section 41.50(b) provides “[a] new ground of
rejection pursuant to this paragraph shall not be considered final for judicial
review.” Section 41.50(b) also provides:
When the Board enters such a non-final decision, the appellant,
within two months from the date of the decision, must exercise
one of the following two options with respect to the new ground
of rejection to avoid termination of the appeal as to the rejected
claims:
(1) Reopen prosecution. Submit an appropriate
amendment of the claims so rejected or new Evidence relating to
the claims so rejected, or both, and have the matter reconsidered
by the examiner, in which event the prosecution will be
remanded to the examiner. The new ground of rejection is
binding upon the examiner unless an amendment or new
Evidence not previously of Record is made which, in the opinion
of the examiner, overcomes the new ground of rejection
designated in the decision. Should the examiner reject the
claims, appellant may again appeal to the Board pursuant to this
subpart.
(2) Request rehearing. Request that the proceeding be
reheard under § 41.52 by the Board upon the same Record. The
request for rehearing must address any new ground of rejection
and state with particularity the points believed to have been
misapprehended or overlooked in entering the new ground of
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rejection and also state all other grounds upon which rehearing
is sought.
Further guidance on responding to a new ground of rejection can be
found in the MPEP § 1214.01.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(1). See 37 C.F.R.
§§ 41.50(f), 41.52(b).
AFFIRMED
37 C.F.R, $ 41.50(b)
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