Ex Parte Morton et al

Patent Trial and Appeal Board

Mar 12, 2019

11587725 (P.T.A.B. Mar. 12, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO.
11/587,725
7066 7590
REED SMITH LLP
Three Logan Square
FILING DATE
06/15/2007
03/14/2019
1717 Arch Street Suite 3100
PHILADELPHIA, PA 19103
FIRST NAMED INVENTOR
David Morton
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.
12-40032-US 8772
EXAMINER
GREENE, NAN A
ART UNIT PAPER NUMBER
1619
NOTIFICATION DATE DELIVERY MODE
03/14/2019 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):
phlipdocketing@reedsmith.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte DAVID MORTON, MARTIN SHOTT, and REBECCA DA VIES 1
Appeal2018-004101
Application 11/587,725
Technology Center 1600
Before RYAN H. FLAX, RACHEL H. TOWNSEND, and
CYNTHIA M. HARDMAN, Administrative Patent Judges.
HARDMAN, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims directed to
inhalable micronized, conditioned, glycopyrrolate compositions. We have
jurisdiction under 35 U.S.C. § 6(b).
We affirm.
1 Appellants identify the real party in interest as V ectura Limited. ( Appeal
Br., 1.) Herein we reference the Oct. 27, 2006 Specification ("Spec."); Jan.
12, 2017 Final Office Action ("Final Act."); Nov. 10, 2017 Appeal Brief
("Appeal Br."); Jan. 10, 2018 Examiner's Answer ("Ans."); and Mar. 9,
2018 Reply Brief ("Reply Br.").
Appeal2018-004101
Application 11/587,725
STATEMENT OF THE CASE
The Specification states that "[i]t is known to provide glycopyrrolate
formulations in the form of dry powder formulations, for administration
using dry powder inhalers." (Spec. p. 1, 11. 11-13.) Appellants' claimed
invention is directed to "dry powder compositions which exhibit improved
stability over time, and methods for producing the same." (Id. at 11. 6-7.)
Claims 33-35, 37, 39-41, 88, 90-92, and 98-103 are on appeal.
Claim 33 is illustrative and reads as follows:
33. A dry powder inhaler comprising
a formulation comprising conditioned, inhalable
micronised glycopyrrolate particles and magnesium stearate in
an amount of from 0.05%-0.5% (w/w) of the formulation
wherein the magnesium stearate is smeared over or fused to the
surfaces of the conditioned, inhalable micronised
glycopyrrolate particles; and
a container for the conditioned, inhalable micronised
glycopyrrolate particles wherein the glycopyrrolate in the
conditioned, inhalable micronised glycopyrrolate particles has
been micronised and then conditioned by exposure to humidity
wherein the humidity is from 30 to 100 percent relative
humidity at a temperature in the range of 5C to 90C for at least
48 hours, and, wherein the container is one or more selected
from the group consisting of a blister, a foil packaging and a
capsule.
(Appeal Br. 18.)
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Application 11/587,725
The Examiner rejected the claims under 35 U.S.C. § I03(a) as obvious
over the combination of Bannister, 2 Staniforth, 3 Keller, 4 Miller, 5 Harmer, 6
Zeng, 7 Ward, 8 and Vemuri, 9 and optionally the Merck Index10 and/or
Lunsford. 11
ANALYSIS
The Examiner found that it would have been obvious to combine the
teachings of the cited prior art to achieve the claimed subject matter, and
that:
one of ordinary skill in the art would have had a reasonable
expectation of success in producing the claimed invention
[because] it would have required no more than an ordinary level
of skill in the art to produce micronized glycopyrrolate product
as now claimed and it would have been within the ordinary
level of skill in the art to formulate the glycopyrrolate including
known excipients such as lactose and magnesium stearate.
2 Bannister et al., US 2003/0068280 Al, published Apr. 10, 2003.
3 Staniforth et al., US 2004/0047810 Al, published Mar. 11, 2004.
4 Keller et al., US 6,645,466 Bl, issued Nov. 11, 2003.
5 Miller et al., WO 03/094890 Al, published Nov. 20, 2003.
6 Harmer et al., WO 2005/025656 Al, published Mar. 24, 2005.
7 Xian Ming Zeng et al., Particulate Interactions in Dry Powder
Formulations for Inhalation, CPCH0663927P, 134--38 (2001).
8 Ward et al., Process-Induced Crystallinity Changes in Albuterol Sulfate
and Its Effect on Powder Physical Stability, 12(5) PHARM. RES. 773-79
(1995).
9 Vemuri et al., WO 00/32165, published June 8, 2000.
10 Entry for glycopyrrolate, The Merck Index® Online, (March 4, 2019),
https://www.rsc.org/ Merck-Index/monograph/m5807 /glycopyrrolate?q=
authorize.
11 Lunsford, C.D., US 2,956,062, issued Oct. 11, 1960.
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Application 11/587,725
(Final Act. 17.) We adopt the Examiner's findings of fact and reasoning
regarding the scope and content of the prior art (Id. at 5-18; Ans. 4--9), and
agree that the claims would have been obvious over the identified prior art
for the reasons the Examiner articulated.
Appellants frame the issues for appeal as follows:
The primary issue for this appeal is whether one of
ordinary skill of the art would have ( 1) known at the time of
invention that micronized glycopyrolate [sic] is extremely
moisture sensitive compared to other dry powder drugs, and (2)
in view of this fact, would have been motivated to pursue a
conditioning step.
(Reply Br. 1.) We address Appellants' arguments below.
Whether one of ordinary skill of the art would have known at the time of
invention that micronized glycopyrrolate is extremely moisture sensitive
compared to other dry powder drugs
In an effort to demonstrate the extreme moisture sensitivity of
glycopyrrolate, Appellants rely on the Specification and on a Declaration of
Matthew Michael James Green dated September 7, 2016 ("Green
Declaration"). (Appeal Br. 5-6.) With regard to Appellants' arguments
based on the Specification, the Examiner found that, although the
Specification sets forth that completely amorphous glycopyrrolate is highly
moisture sensitive, this implies that crystalline glycopyrrolate is less
moisture sensitive. (Final Act. 23-24.) The Examiner further found that the
prior art glycopyrrolate is crystalline, and thus "is not the completely
amorphous form that is very hygroscopic as discussed in the instant
application as filed." (Id. at 24.) With regard to the Green Declaration, the
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Application 11/587,725
Examiner stated that he "sees no objective factual evidence that would lead a
reasonable person to the conclusion that applicants have drawn." (Id.)
We agree with the Examiner that Appellants have not presented
persuasive evidence that one of ordinary skill of the art would have known at
the time of invention that micronized glycopyrrolate is extremely moisture
sensitive compared to other dry powder drugs. Appellants' arguments and
evidence do not establish that one of ordinary skill in the art would have
known of this purported property of glycopyrrolate at the time of invention.
A reasonable expectation of success ( or lack thereof) "must be founded in
the prior art." Velander v. Garner, 348 F.3d 1359, 1363 (Fed. Cir. 2003)
(citing In re Vaeck, 947 F.2d 488,493 (Fed. Cir. 1991)). Yet neither the
statements Appellants cite in the Specification (see Appeal Br. at 5, citing
Spec. p. 2, 11. 22-23 and p. 3, 11. 14--16), nor the experimental work in the
Green Declaration, are grounded in a timeframe contemporaneous with the
invention. And if the purported exceptional property was not known in the
prior art, it could not have undermined the reasonable expectation of
success, as Appellants contend.
In their Reply Brief, Appellants for the first time cite paragraph 8 of
the Green Declaration to further support the assertion that a person of
ordinary skill working with micronized glycopyrrolate would have known of
the drug's extreme moisture sensitivity. Paragraph 8 of the Green
Declaration states in relevant part:
If not already known by a skilled person prior to working
with freshly milled glycopyrrolate, one of ordinary skill in the
art would quickly understand that freshly milled glycopyrrolate,
because of its moisture sensitivity, is different from other
inhaled drug powders ....
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(Green Declaration ,r 8.) This statement does not establish, by a
preponderance of the evidence, that this property of glycopyrrolate was
known to persons of ordinary skill in the art at the time of the invention.
Rather, it leaves open whether this property was known ("[i]f not already
known by a skilled person .... ").
Paragraph 8 of the Green Declaration also suggests that a person of
ordinary skill in the art would have quickly recognized glycopyrrolate's
extreme moisture sensitivity upon milling. This statement, however, is not
corroborated by the prior art of record. For example, although the Bannister
and Staniforth references teach freshly milled glycopyrrolate (see, e.g.,
Bannister ,r 45; Staniforth ,r 101 ), neither mention this supposed exceptional
property. For this reason, we accord this statement little weight. See In re
Am. Acad. of Sci. Tech Ctr., 367 F.3d 1359, 1368 (Fed. Cir. 2004) ("[T]he
Board is entitled to weigh the declarations and conclude that the lack of
factual corroboration warrants discounting the opinions expressed in the
declarations."); Velander, 348 F.3d at 1371 ("In giving more weight to prior
publications than to subsequent conclusory statements by experts, the Board
acted well within [its] discretion.").
Accordingly, Appellants do not persuade us of any error in the
Examiner's finding that "[t]he record does not establish that, at the time of
the claimed invention, it was conventional wisdom that glycopyrrolate [is]
so moisture sensitive that one of ordinary skill in the art would have avoided
the indicated treatment [of Zeng, Ward and Vemuri]." (Ans. 6-7, emphasis
in original.)
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Appellants also take issue with the Examiner's treatment of the Green
Declaration. First, Appellants assert that the Examiner improperly dismissed
the Green Declaration and gave it no weight. (See, e.g., Appeal Br. 10-11;
Reply Br. 3.) The Examiner, however, indicates that he did consider the
declaration, but ultimately found it insufficient to overcome the motivation
to condition glycopyrrolate, with a reasonable expectation that doing so
would reduce its moisture sensitivity. (See, e.g., Final Act. 19-20, 24--25;
Ans. 6-7.) For the reasons discussed above, we agree that the Declaration is
insufficient to overcome the strongprimafacie case of obviousness. See,
e.g., Velander, 348 F.3d at 1371 ("It is within the discretion of the trier of
fact to give each item of evidence such weight as it feels appropriate.").
Second, Appellants argue that in rejecting the Green Declaration, the
Examiner placed an "improper burden" on Appellants to rebut an "unsupported
factual assertion" that one of ordinary skill in the art "understood
glycopyrrolate to behave similarly to other inhalational drugs." (Reply 3--4.)
We are not persuaded that the Examiner required Appellants to rebut such an
understanding. Rather, the Examiner simply found unpersuasive
Appellants' testimony and argument that glycopyrrolate was known to be
exceptional. Cf Velander, 348 F.3d at 1370 (rejecting argument that in
finding rebuttal testimony unpersuasive, the Board improperly shifted the
burden of proof).
Even assuming that Appellants had established that one of ordinary
skill of the art would have known at the time of invention that micronized
glycopyrrolate is extremely moisture sensitive compared to other dry powder
drugs, Appellants have not persuaded us that this fact alone would
undermine a reasonable expectation that conditioning glycopyrrolate would
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improve its stability. Nothing in Zeng, Ward, or Vemuri teaches that
conditioning is unworkable for drugs that are extremely moisture sensitive.
Indeed, these references teach that conditioning is useful for drug substances
that have amorphous regions introduced by milling, because "amorphous
regions have the propensity to absorb significant quantities of water," and
conditioning will convert these amorphous regions to more stable crystal
regions. (Ward 773; see also Zeng 137-38.) In other words, the prior art
teaches that conditioning will benefit hygroscopic drugs by reducing their
propensity to absorb water, which supports a reasonable expectation of
success. Appellants have not identified any prior art teaching or suggestion
that a drug can be too hygroscopic to benefit from conditioning.
In sum, having considered and weighed the prior art and all of the
Appellants' arguments and evidence against obviousness, we agree with the
Examiner's finding that "Appellants followed the teachings of the prior
art with the species glycopyrrolate and achieved the results that the
prior art suggest one would have achieved." (Ans. 7-8, emphasis in
original.)
Whether one of ordinary skill of the art would have been motivated to
condition the glycopyrrolate
Appellants also assert that "[t]he Examiner has failed to articulate a
rational apparent reason why one of ordinary skill in the art would perform
the step of conditioning the micronized glycopyrrolate." (Appeal Br. 15.)
According to Appellants, because neither Bannister nor Staniforth mention
any problem with storage stability, and because "Keller teaches that any
problem with storage stability due to moisture sensitivity is addressed by the
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use of magnesium stearate which is taught by both Bannister and
Staniforth," "one of ordinary skill in the art would not have recognized a
storage stability problem and would therefore have no reason to attempt to
improve upon Bannister, Staniforth and/or Keller using Zeng, Ward or
Vemuri." (Appeal Br. 13-14.)
In response, the Examiner states that the prior art indicates that
inhaled pharmaceutical drug products must be micronized, but recognizes
that the micronization process introduces thermodynamically unstable
amorphous regions on the surface of the micronized particles. (Ans. 6.) The
Examiner found that the prior art teaches deliberately converting any
unstable amorphous regions to more stable crystalline regions by
conditioning the drug, i.e., exposing it to moisture in a controlled manner.
(Id.) The Examiner concludes that in view of these teachings, the prior art
provides a clear motivation to expose micronized (inhalation) drug products
such as glycopyrrolate to moisture in a controlled manner as claimed by
Appellants. (Id.)
We agree with the Examiner that a person of ordinary skill in the art
would have been motivated to condition micronized glycopyrrolate, even in
the absence of any statement in Bannister, Staniforth, or Keller that
micronized glycopyrrolate had a storage stability issue. As noted by the
Examiner ( and not disputed by Appellants), the prior art teaches that
formation of unstable amorphous regions is unavoidable if mechanical
micronization is employed. (Final Act. 12.) As the Examiner explained,
while Keller does teach that magnesium stearate is used to improve storage
stability, the mechanism taught by Keller is distinct from that of addressing
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the known issue caused by amorphous regions in a micronized drug product.
(Ans. 9.) Accordingly, we are not persuaded that Bannister, Staniforth, and
Keller's silence about storage stability issues undermines the Examiner's
finding that a person of ordinary skill in the art would have recognized a
storage stability issue caused by the presence of amorphous regions, and
therefore would have been motivated to combine the conditioning process
taught in the prior art with micronized glycopyrrolate.
SUMMARY
We affirm the Examiner's rejection of claims 33-35, 37, 39-41, 88,
90-92, and 98-103 under 35 U.S.C. § 103(a) as obvious over the
combination of Bannister, Staniforth, Keller, Miller, Harmer, Zeng, Ward,
and Vemuri, and optionally the Merck Index and/or Lunsford.
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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