Ex Parte Beyerinck et al

Patent Trial and Appeal Board

Feb 11, 2019

10910115 (P.T.A.B. Feb. 11, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
10/910,115 08/03/2004 Ronald Arthur Beyerinck
24197 7590 02/13/2019
KLARQUIST SPARKMAN, LLP
121 SW SALMON STREET
SUITE 1600
PORTLAND, OR 97204
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
ATTORNEY DOCKET NO. CONFIRMATION NO.
8191-92854-01 8003
EXAMINER
BREDEFELD, RACHAEL EV A
ART UNIT PAPER NUMBER
1611
NOTIFICATION DATE DELIVERY MODE
02/13/2019 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):
docketing@klarquist.com
AS CChair@klarquis t. com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte RONALD ARTHUR BEYERINCK, DANIEL ELMONT DOBRY,
DWAYNE THOMAS FRIESEN, DANA MARIE SETTELL, and
RODERICK JACK RA Y 1
Appeal2018-003430
Application 10/910,115
Technology Center 1600
Before DEMETRA J. MILLS, ULRIKE W. JENKS, and
ROBERT A. POLLOCK, Administrative Patent Judges.
POLLOCK, Administrative Patent Judge.
DECISION ON APPEAL
Appellants appeal under 35 U.S.C. § 134(a) from the final rejection of
claims 1, 3, 4, 9, 11-13, and 17. We have jurisdiction under 35 U.S.C.
§ 6(b ).
We reverse.
STATEMENT OF THE CASE
Appellants' invention relates to a process for forming a spray-dried
pharmaceutical composition comprising a solid amorphous dispersion of
1 Appellants identify the Real Party in Interest as Bend Research, Inc. App.
Br. 3.
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Application 10/910, 115
low-solubility drug and a copolymer. Spec. 3: 1-8. "A spray solution is
formed by dissolving the low-solubility drug and the polymer in a solvent,"
which is "sprayed through the atomizer into the chamber to form droplets
having a volume average size of less than 500 µm. A drying gas is flowed
through the inlet at a flow rate and a temperature TIN such that the droplets
solidify in less than about 20 seconds." Id. at 3:6-11. According to the
Specification,
retaining a small amount of residual solvent vapor in the drying
gas can improve the physical properties of the resulting spray
dried dispersions. This is a surprising result, since the
conventional wisdom has held that the drying gas should be as
dry as possible in order to achieve rapid evaporation of solvent.
In particular, using a drying gas containing a small amount of
solvent can decrease the residual solvent and specific volume of
the solid amorphous dispersion particles exiting the drying
chamber while still producing a homogeneous solid amorphous
dispersion. Preferably, the amount of solvent vapor in the
drying gas ranges from 5 to about 50 wt%.
Id. at 32:4--12.
Claim 1, the sole independent claim before us, recites (italics added):
1. A process for forming a pharmaceutical composition
comprising a solid amorphous dispersion comprising a low-
solubility drug and a polymer, comprising the steps of:
(a) providing a drying apparatus having an atomizer in fluid
communication with a drying chamber, said drying chamber
having an inlet and an outlet;
(b) forming a spray solution by dissolving said low-solubility
drug and said polymer in a solvent, wherein said polymer is
an amphiphilic polymer;
( c) spraying said spray solution through said atomizer into said
drying chamber to form droplets having a volume average
size of less than 500 gm;
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( d) flowing a drying gas through said inlet at a flow rate and a
temperature TIN such that (i) said droplets solidify in less
than about 20 seconds to form said solid amorphous
dispersion of said low-solubility drug and said polymer, and
(ii) a solvent vapor-laden drying gas is formed and
exhausted from said outlet;
(e) removing solvent vapor from said exhausted solvent vapor-
laden drying gas to form a solvent vapor-depleted drying
gas containing from 5 to about 25 wt% of said solvent in
vapor form; and
(f) directing said solvent vapor-depleted drying gas to said
inlet so as to combine it with said drying gas,
wherein the feed rate of said spray solution is at least 10 kg/hr,
said feed rate of said spray solution and TIN of said drying gas
are controlled so that said drying gas at said outlet has a
temperature T ouT that is less than the boiling point of said
solvent, and wherein said solid amorphous dispersion is
substantially homogenous, said T ouT is less than the glass
transition temperature of said solid amorphous dispersion, and
wherein the bulk specific volume of said dispersion is less than
the bulk specific volume of a dispersion made with no solvent
vapor in said drying gas.
I. Claims 1, 3, 4, 12, 13, and 17 stand rejected under pre-AIA 35 U.S.C.
§ 103(a) as unpatentable over the combination of Beyerinck2 and GB
'635 3 as evidenced by MSDS. 4
2 Beyerinck et al., WO 03/063821 A2, published Aug. 7, 2003.
3 GB 475,635, accepted Nov. 23, 1937.
4 Material Safety Data Sheet Acetone MSDS, ScienceLab.com, last updated
November 6, 2008.
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II. Claims 1, 3, 4, 12, 13, and 17 stand rejected under pre-AIA 35 U.S.C.
§ 103(a) as unpatentable over the combination of Babcock5 and GB '635
as evidenced by MSDS.
III. Claims 9 and 11 stand rejected under pre-AIA 35 U.S.C. § 103(a) as
unpatentable over the combination of Babcock and GB '63 5 as
evidenced by MSDS, and further over Deis 6,7
FINDINGS OF FACT
FF 1. Beyerinck discloses a process for making spray-dried solid amorphous
dispersions of drugs in concentration-enhancing polymers, including
vinyl polymers and copolymers. Beyerinck, Abstract, 2:26-3:3, 13:8-17.
The solvent may be an organic solvent such as acetone. Id. at 30:21-35.
"After both the drug and the polymer have been dissolved, the solvent is
rapidly removed by evaporation in the spray-drying apparatus, resulting
in the formation of a substantially homogeneous, solid amorphous
dispersion." Id. at29:15-18.
FF2. Babcock discloses compositions of glycogen phosphorylase inhibitor,
including solid amorphous dispersions of the drug, with concentration
enhancing polymers. Babcock, Abstract 19:30-20:28. "A preferred
method of forming the dispersion is by dissolving the drug and dispersion
polymer in a common solvent, then removing the solvent by spray-drying
or spray-coating." Id. at 21 :32-35; 22:4--23 :2. Babcock disclosed the
5 Babcock et al., WO 01/68092 A2, published Sept. 20, 2001.
6 Ronald C. Deis, Spray-Drying Innovative Use of an Old Process, Design
Elements 1-7 (May 1, 1997).
7 Deis is asserted with respect to dependent claim 9 only and a separate
discussion of this reference is not necessary to our Decision.
4
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Application 10/910, 115
use of polymers including vinyl polymers and copolymers, and organic
solvents such as acetone. See id. at 12:4--22, 22:30-35, 27: 19--28:5.
Babcock further teaches that drying time of sprayed droplets is a function
of droplet size and the temperature and flow rate of the drying gas. Id. at
23:3-15. "For some mixtures of drug/dispersion polymer/solvent[] rapid
drying generally leads to a more uniform, homogeneous composition, as
opposed to the generally less desirable separation into drug-rich and
polymer-rich phases." Id. at 23:15-20.
FF3. GB '63 5 is directed to a spray drying and solvent recovery system for
the production of thermoplastic heat-sensitive materials vinyl polymers
"by heating and spray drying, which comprises precipitating and drying
said materials in the presence of hot inert gas at a temperature below their
softening point, recovering the volatile solvents and re-cycling the inert
gas[.]" GB '635 1 :89--97; see id. at 1 :32-35. GB '635 illustrates the
invention as "a process for spray-drying a solution in acetone of a vinyl
resin resulting from the conjoint [polymerization] of vinyl chloride and
vinyl acetate[.] Id. at 4:66-72. In this embodiment, recycled gases
flowing to the desiccator "may contain ... around 3 .1 % of acetone" by
volume. Id. at 4:110-114.
ANALYSIS
This case was previously before us in Appeal No. 2013-006476,
issued December 21, 2015 ( the "Prior Appeal"). As in the Prior Appeal, the
Examiner finds that Beyerinck and Babcock, individually, teach all steps of
the asserted claims but for "removing solvent vapor from the drying gas to
form a solvent vapor depleted gas containing from about 5-50 wt.% of said
solvent in vapor form and directing said solvent vapor-depleted drying gas to
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said inlet so as to combine it with said drying gas" (i.e., steps ( e) and ( f) of
claim 1), as taught by GB '635. Final Rej. 8 4---6, 12-13. The Examiner
concludes that it would have been obvious to combine the teachings of
Beyerinck or Babcock with the drying gas recycling system of GB '635 to
arrive at the claimed invention. Id. at 5, 9-10.
In particular, the Examiner finds that one of ordinary skill would have
been motivated to combine these teachings "to reduce waste and be more
environmentally friendly[;] ... by not supplying a fresh drying gas
constantly, an artisan of ordinary skill would be able to employ a more
efficient method and save costs, especially if energy costs are high." Id. at
5, 9. With respect to the requirement that the recycled drying gas of claim 1
contain a specified percentage of "solvent, the Examiner finds that the
"around 3 .1 %" of solvent taught by GB '63 5 is close enough as to be
patentably indistinct from the range claimed absent evidence that the
claimed concentration is critical. See id. at 5, 9-10 (citing MPEP 2144.05
and Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 227 (Fed.
Cir. 1985)).
As articulated by the Examiner, our Prior Appeal indicated "that the
Dobry Declaration ... failed to demonstrate that the presence of 3 .1 %
solvent vapor in the drying gas taught in GB '635 does not lead to
significant, unexpected results." Ans. 6 ( citing Prior Appeal, 9-10).
According to the Examiner, Appellants have also failed to do so in the
instant Appeal. Id. Applicants instead argue that one of ordinary skill in the
art in the field of pharmaceutical manufacturing would not have been
8 Final Office Action mailed Feb. 22, 2017 ("Final Rej.").
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motivated to combine Beyerinck or Babcock and GB '635 with a reasonable
expectation of success because the recycled drying gas in GB '635 would
have contained undesirable levels of solvent. See App. Br. 7-8; Reply Br. 2.
In particular, Appellants supplement the Dobry Declaration with three
new declarations, the Baumann Declaration, 9 the Beyerinck Declaration, 10
and the Friesen Declaration, 11 "to explain why one of ordinary skill in the
[pharmaceutical arts] would actually have been demotivated to make the
proposed combination." See Reply Br. 2. Appellants argue, for example,
that the Baumann Declaration explains "why the conventional wisdom was
that the drying gas for spray drying technology (particularly for solid
amorphous drug dispersions) should be as free of solvent as possible,"
whereas the Beyerinck and Friesen Declarations assert that persons of
ordinary skill in the art at the time of the claimed invention followed this
conventional wisdom in the manufacture of pharmaceutical particles "to
provide a solid amorphous dispersion with [the] desirable physical
properties." App. Br. 7. We note, in particular, Mr. Baumann's explanation
that one of ordinary skill in the art would have sought to keep solvent levels
in the drying gas as low as possible to facilitate rapid drying, reduce
tackiness, and minimize drug re-crystallization (loss of amorphous-state
characteristics). See Baumann Declaration ,r 7.
9 Declaration of John M. Baumann under 37 C.F.R. § 1.132, dated Feb. 18,
2016.
10 Declaration of Ronald A. Beyerinck under 37 C.F.R. § 1.132, dated Feb.
18,2016.
11 Declaration of Dwayne T. Friesen under 37 C.F.R. § 1.132, dated Feb. 18,
2016.
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In response, the Examiner states that the Friesen and Beyerinck
Declarations "are merely opinion Declarations" and "only provide
conclusions without any probative value, i.e.[,] evidence of unexpected
results, commercial success, solution of a long-felt need, inoperability of the
prior art, etc." Ans. 6-7. The Examiner further argues that "the Bauman[n]
Declaration is insufficient in that it fails to address the criticality of the
claimed range of solvent vapor in the drying gas" and, thus, fails to
demonstrate unexpected results. Id. at 7. We do not find the Examiner's
arguments persuasive.
We discern no reason to doubt the veracity of Appellants'
Declarations. Moreover, with respect to the criticality of the claimed range
of solvent vapor in the drying gas, the Friesen, Beyerinck, and Baumann
Declarations establish that one of ordinary skill in the relevant art would
have followed the conventional wisdom of using dry drying gas in the
manufacture of pharmaceutical particles and would not have considered the
recycled drying gas taught by GB '635 sufficiently dry. As noted by
Appellant's however, the Declarations are not designed to show unexpected
results but "to explain why one of ordinary skill in the art would actually
have been demotivated to make the proposed combination." See Reply at 2.
Evidence suggesting reasons to combine cannot be viewed in a vacuum apart
from evidence suggesting reasons not to combine. Arctic Cat Inc. v.
Bombardier Recreational Prod. Inc., 876 F.3d 1350, 1363 (Fed. Cir.
2017), cert. denied, 139 S. Ct. 143,202 L. Ed. 2d 34 (2018). Having
considered the evidence of record, we find that Appellants have reasonably
established that one of ordinary skill in the relevant art would not have
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combined the asserted references with a reasonable expectation of success in
achieving the claimed invention.
The rejections of record are reversed.
SUMMARY
We reverse the rejection of claims 1, 3, 4, 12, 13, and 17 under
35 U.S.C. § 103(a) as unpatentable over the combination ofBeyerinck
and GB '635 as evidenced by MSDS.
I. We reverse the rejection of claims 1, 3, 4, 9, 11-13, and 17
under 35 U.S.C. § 103(a) as unpatentable over the combination of
Babcock and GB '635 as evidenced by MSDS, and further in view of
Deis (with respect to claims 9 and 11 ).
REVERSED
9