Ex Parte Lindell et al

Patent Trial and Appeal Board

Oct 29, 2018

11686842 (P.T.A.B. Oct. 29, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
11/686,842 03/15/2007
23377 7590 10/31/2018
BAKER & HOSTETLER LLP
CIRA CENTRE 12TH FLOOR
2929 ARCH STREET
PHILADELPHIA, PA 19104-2891
UNITED ST A TES OF AMERICA
FIRST NAMED INVENTOR
Katarina E.A. Lindell
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.
103669.000316 7097
EXAMINER
THAKOR, DEV ANG K
ART UNIT PAPER NUMBER
1619
NOTIFICATION DATE DELIVERY MODE
10/31/2018 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):
eofficemonitor@bakerlaw.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte KA TARIN A E.A. LINDELL, BENGT A. BOSSON,
GUNNAR A. BERGENGREN, and ANETTE K. SCHLUTER
Appeal2017-001569
Application 11/686,842
Technology Center 1600
Before TONI R. SCHEINER, DEMETRA J. MILLS, and JOHN G. NEW,
Administrative Patent Judges.
MILLS, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134. The Examiner has rejected
the claims for obviousness. We have jurisdiction under 35 U.S.C. § 6(b ).
We affirm.
Appeal2017-001569
Application 11/686,842
STATEMENT OF CASE
The following claim is representative. 1
1. A method for delivering nicotine to a subject, the
method comprising:
administering a liquid pharmaceutical composition
comprising free base form nicotine into the oral cavity of a
subject by spraying, dropping or pipetting thereby providing
oral transmucosal delivery of nicotine to the subject without
chewing or sucking,
said composition having an alkaline pH and further
comprising one or more buffers present in an amount sufficient
to confer sufficient buffering capacity on the composition such
that the composition transiently increases the pH of liquid in the
oral cavity of said subject by about 0.3 to about 4 pH units and
reduces the subject's urge to smoke within 30 minutes of
administration by allowing the nicotine to be systematically
absorbed by buccal uptake,
the composition comprising from about 0.05 to about 10
mg of nicotine calculated as the free base form of nicotine per
200 microliters of composition,
the composition comprising less than 25 wt% alcohol.
1 Appellant submitted an Appeal Brief and Supplemental Appeal Brief,
cancelling claims. The Examiner never acknowledged these claim
cancellations. Thus, the pending claims are those submitted Sept. 22, 2014.
1-7, 9-23, 25 and 27-51 are pending.
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5. The method of claim 1, wherein administration of
said composition is by spraying under the tongue.
Office Act. September 22, 2014.
Cited References
Perno et al. us 4,579,858 Apr. 1, 1986
Rose et al. us 4,920, 989 May 1, 1990
Jones us 5,656,255 Aug. 12, 1997
Monte us 5,810,018 Sept. 22, 1998
Von Wielligh us 6,024,097 Feb. 15,2000
Harris et al., Drug Delivery via the Mucous Membranes of the Oral Cavity
Vol. 81 Number 1 J. PHARMACEUTICAL SCIENCES 1-10 (Jan. 1992).
Tomar et al., Review of the evidence that pH is a determinant of nicotine
dosage from oral use of smokeless tobacco 6 TOBACCO CONTROL 219-225
(1997).
Grounds of Rejection
1. Claims 1--4, 6, 7, 9-14, 16-20, 22, 24, and 26--48 are rejected
under 35 U.S.C. § 103(a) as being unpatentable over Rose and
Tomar.
2. Claims 5 and 16 under 35 U.S.C. § 103(a) are rejected as being
unpatentable over Rose, Tomar, and Harris.
3. Claims 1--4, 6, 7, 9-14, 16, 17, 20, 22, 24, 26-36, and 41--47 under
35 U.S.C. § 103(a) are rejected as being unpatentable over Monte
and Rose.
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4. Claims 37--40 and 48 under 35 U.S.C. § 103(a) are rejected as
being unpatentable over Monte, Tomar and Rose.
5. Claims 5 and 16 under 35 U.S.C. § 103(a) are rejected as being
unpatentable over Monte, Tomar and Harris.
6. Claims 1--4, 6, 7, 9-14, 16, 17, 20-36, and 41--47 under 35 U.S.C.
§ 103(a) are rejected as being unpatentable over Von Wielligh,
Tomar and Rose.
7. Claims 28, 29, 31, 32, 34, 36, 38, 40, and 47 are rejected under 35
U.S.C. § 112(a) or 35 U.S.C. 112 (pre-AIA), first paragraph, as
failing to comply with the written description requirement.
FINDINGS OF FACT
The Examiner's findings of fact are set forth in the Answer at pages
3-22. The following facts are highlighted.
1. Rose teaches a method for delivering nicotine to a subject, the
method comprising the steps of administering a liquid
pharmaceutical composition comprising nicotine into the oral
cavity of a subject by spraying, i.e., via oral transmucosal delivery
without chewing or sucking ( column 16, line 66). Rose does not
teach an alkaline pH for the composition or the presence of a
buffer in the composition used in the method. Ans. 7.
2. Monte teaches a method for delivering nicotine to a subject, the
method comprising: administering a liquid pharmaceutical
composition comprising nicotine into the oral cavity of a subject
by spraying, dropping or pipetting thereby providing oral
transmucosal delivery of nicotine to the subject without chewing or
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sucking, said composition having an alkaline pH and further
comprising one or more buffers present in an amount sufficient to
confer sufficient buffering capacity on the composition such that
administration of the composition transiently increases the pH of
liquid in the oral cavity of said subject by about 0.3 to about 4 pH
units and reduces the subject's urge to smoke within 30 minutes of
administration by allowing the nicotine to be systematically
absorbed by buccal uptake. (col. 2, 11. 25-30; col. 4, 11. 15-20; col.
5, 11. 39).
3. Monte teaches a concentration of 0-2% for the nicotine but does
not teach the spray volume. Col. 3, 11. 50-60; Ans. 20.
4. Rose teaches that for a concentration range similar to that of Monte
(i.e., 0.01 %-3%; column 16, line 58 and column 8, line 61 ), a
volume of 0.27 microliters to 300 micro liters is used for the spray
because the desired dose of nicotine is 0.008 mg to 0.03 mg per
inhalation (Rose, col. 9, 1. 44).
5. Rose teaches nicotine in free base form. Col. 14, 1. 28-30.
6. Monte teaches nicotine in free base form. Col. 4, Ex. 1
7. Von Wielligh teaches a method for delivering nicotine to a subject,
the method comprising administering a liquid pharmaceutical
composition comprising nicotine ( col. 4, 1. 35) by spray
administration to the oral cavity ( col. 4, 11. 52-55).
8. Tomar teaches that the absorption of nicotine in the oral mucosa is
enhanced at alkaline pH (abstract) and that the inclusion of
buffering agents (i.e., sodium carbonate and bicarbonate) in
nicotine-containing gum chewed orally for nicotine replacement
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therapy increases the pH of the oral environment and thus
facilitates the absorption of nicotine ("nicotine replacement
studies;" page 223, left column). In particular, Tomar teaches that
oral mucosal uptake of nicotine is increased by 30% from pH 7 to
pH 9 ("human studies," page 222, left column).
PRINCIPLES OF LAW
In making our determination, we apply the preponderance of the
evidence standard. See, e.g., Ethicon, Inc. v. Quigg, 849 F.2d 1422, 1427
(Fed. Cir. 1988) (explaining the general evidentiary standard for proceedings
before the Office).
"The combination of familiar elements according to known methods
is likely to be obvious when it does no more than yield predictable results."
KSR Int'! Co. v. Teleflex Inc., 550 U.S. 398,416 (2007).
Moreover, "obviousness requires a suggestion of all limitations in a
claim." CFMT, Inc. v. Yieldup Intern. Corp., 349 F.3d 1333, 1342 (Fed. Cir.
2003) (citing In re Royka, 490 F.2d 981,985 (CCPA 1974)).
"The fact that the motivating benefit comes at the expense of
anotherbenefit ... should not nullify its use as a basis to modify the
disclosure of one reference with the teachings of another. Instead, the
benefits, both lost and gained, should be weighed against one another."
Medichem S.A. v. Rolabo S.L., 437 F.3d 1157, 1165 (Fed. Cir. 2006).
Obviousness Rejection
For purposes of expediency and avoidance of redundancy in this
Decision, Rejections 1, 3, 4, and 6, as set forth in the grounds of rejection,
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are combined, and addressed below. Appellants put forth many of the same
arguments for each of these rejections. Arguments not shared by all of the
rejections, or arguments with respect to individual reference will appear
separately, in specific paragraphs.
Essentially, Rose, Monte and Von Wielligh teach liquid formulations
of nicotine. FF 1, 2, 5. Rose and Monte additionally teach that the nicotine
may be in the form of a free base. FF 5, 6. The Examiner relies on Tomar
for the teaching that it is known in the art to adjust the pH of nicotine to
increase its absorption rate. P. 222, col. 1.
Appellants contend that the prior art of Jones and Perno teaches away
from the claimed invention. App. Br. 11. Appellants argue that Jones
expressly taught acidic, not alkaline compositions for nicotine delivery. Id.
Appellants argue that Perno mandated use of an acidic nicotine delivery
environment over an alkaline one. Id. Appellants repeat this argument for
each of the combinations of primary references.
The Examiner responds, arguing that the art of record does not teach
away from the proposed reference combinations. The Examiner argues that
the disclosure of F erno is limited to nasal administration and that side effects
of Ferno's composition administration include nasal burning and intensive
sneezing. Ans. 34. The Examiner argues that Appellants have provided no
evidence or reasoning for why this might be the case, or given specific
examples of the kind of adverse effects that could actually be expected when
orally consuming an alkaline solution. Id.
The primary issue is: Does the evidence of record teach away from
the claimed invention?
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ANALYSIS
We agree with the Examiner's fact finding, statement of the rejection
and responses to Appellants' arguments as set forth in the Answer. We find
that the Examiner has provided evidence to support a prima facie case of
obviousness. We provide the following additional comment to the
Examiner's argument set forth in the Final Rejection and Answer.
We are not persuaded by Appellants' arguments that Jones and F emo
teach away from the claimed invention. Appellants have not established
with evidence that the nasal symptoms or side effects of acidic nicotine
compositions would also be present in the oral cavity with administration of
a nicotine composition buffered to pH levels of 8-9. Attorney argument
cannot take the place of evidence. In addition, Tomar indicates that oral
delivery of nicotine with increased alkalinity promotes the absorption of
nicotine and increases its physiological effects. Tomar further states that,
"In a ... study, Beckett, Gorrod, and Jenner examined the buccal absorption
of various tobacco alkaloids and found a strong effect of increased pH on
absorption of nicotine-virtually none was absorbed at pH 5.5, about 10% at
pH 7, and more than 30% at pH 9." Tomar, p. 222, col. 1. Tomar further
suggests the buffering of nicotine with sodium carbonate. Tomar, p. 223,
col. 1. One of ordinary skill in the art would readily recognize under
scientific pH principles that more buffering of nicotine would decrease the
acidity of nicotine in a formulation, as well side effects associated with
acidic formulations of nicotine. Moreover, one of ordinary skill in the art
would optimize the result effective variable of pH to balance the nicotine
absorption rate with side effects associated with acidic pH. ("[D]iscovery of
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an optimum value of a result effective variable in a known process is
ordinarily within the skill of the art." (citations omitted)). In re Peterson,
315 F.3d 1325, 1330 (Fed. Cir. 2003).
In the present case, "[t]he fact that the motivating benefit comes at the
expense of another benefit ... should not nullify its use as a basis to modify
the disclosure of one reference with the teachings of another. Instead, the
benefits, both lost and gained, should be weighed against one another."
Medichem S.A. v. Rolabo S.L., 437 F.3d 1157, 1165 (Fed. Cir. 2006). Thus,
in the present case, the motivating benefit of increased nicotine absorption
would tend to reduce side effects associated with acidic formulations like
those of Jones and Perno. The benefit of increased nicotine absorption is
weighed against side effects by one of ordinary skill in the art, who desires
to find the best formulation balance.
We also find that the Examiner never stated that Jones teaches away
from the claimed invention in the manner suggested by Appellants. In the
Final Rejection dated June 19, 2015, the Examiner stated that Jones was
only cited for peak blood nicotine levels occurring around 15 minutes after
administration and other references were relied on to teach an alkaline
nicotine composition for oral delivery. P. 29. We agree with the Examiner
and do not find that the Examiner agreed that Jones taught away from the
claimed invention.
With respect to Tomar, Appellants argue that none of Tomar's
examples address buffered oral nicotine sprays. App. Br. 15. Appellants
argue that Tomar does not contemplate liquid formulations that include free
base nicotine and a separate buff er. The Examiner responds, arguing that
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Tamar [sic, Tomar] generally teaches that nicotine absorption in
mucosal tissue is enhanced at higher pH, which clearly provides
motivation to increase the pH of any formulation used to deliver
nicotine to the oral mucosa as relied on in the rejection, not only for
gum formulations. Appellant has not provided any reasoning or
rationale for why the general teaching of Tamar [ sic, Tomar]
regarding pH sensitivity of nicotine delivery to the oral mucosa would
not motivate one of ordinary skill in the art at the time of invention to
adjust the pH of an oral spray formulation, which also delivers
nicotine to the oral mucosa ...
Ans. 45, et. seq.; Tomar, p. 222, col. 1. Tomar states that, "Beckett and
Rossie ... noted that the oral mucosa behaves similarly to other biological
lipoidal membranes relative to its penetration by drugs." Tomar, p. 222, col.
1. The Examiner argues that, Tomar "generally teaches that nicotine
absorption in mucosal tissue is enhanced at higher pH; this mechansism [ sic,
mechanism] is not dependent on the particular dosage form because it
depends on the oral pH." Ans. 46. The Examiner relies on Rose and Monte
for free base, liquid, nicotine formulations for oral delivery, not Tomar. In
addition, Appellants err in attacking the references individually, as the
rejection is based on a combination of references. See In re Merck & Co.,
Inc,., 800 F.2d 1091, 1097 (Fed. Cir. 1986). The references cannot be read in
isolation, but must be read for what they teach in combination with the prior
art as a whole. See id.
Appellants argue that the Examiner did not honor the well-settled rule,
including the rule that "a compound can be patented on the basis of its
properties." In re Chupp, 816 F.2d 643, 646 (Fed. Cir. 1987). Appellants
further cite Ex Parte Vigano, No. 2010-007666, 2011 WL6960346, *2-3
(BP AI 2011) in support of this proposition. App. Br. 21. We are not
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persuaded by Appellants' argument. We find that the Examiner has
established a prima facie case of obviousness on the cited combinations of
references, and that the Examiner properly shifted the burden of proof to
Appellants to show that the oral, liquid, nicotine formulations of Rose,
Monte and Von Wielligh, at the buffered nicotine pH range suggested by
Tomar, would have untoward side effects in the oral cavity at the buffered
pH ranges of Tomar. Appellants failed to provide such evidence. The
evidence of Jones and Perno is insufficient to show side effects in the oral
cavity at the buffered pH range suggested by Tomar.
With respect to claim 35, Appellants argue that the Examiner
misinterprets the reference and Appellants' disclosure, and misapplies the
doctrine of inherency. App. Br. 19, 22. Appellants argue, in particular, that
Figure 3 of
Rose provides some disclosure related to craving reduction.
But (1) that figure relates to the effect of transdermal - not oral -
administration of nicotine to a subject and (2) that figure shows that
transdermal administration of 8 mg of nicotine resulted in a craving
reduction of less than 5% within 30 minutes of administration,
which is far inferior to appellants' claimed reduction of 20% within 2
minutes of administration. Thus, Rose does not provide any
disclosure regarding appellants' claimed craving reduction as a
function of time based on oral administration of nicotine.
App. Br. 22.
The Examiner responds arguing,
it is not necessary for Rose to provide any disclosure regarding
appellants' claimed craving reduction as a function of time based on
oral administration of nicotine, because these properties would
necessarily be associated with performing the method of the rejection.
[C]lear and specific motivation is provided by Tamar [sic, Tomar]
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to modify the Rose to arrive at the claimed invention, and thus the
elements of the claimed subject matter, i.e., oral nicotine spray and
inclusion of a buffer in an oral dosage form to increase oral pH and
thereby increase nicotine absorption across the oral mucosa, were
known at the time of invention. Because the structure of the obvious
composition is substantially identical to that of the claimed
composition, it would necessarily have the same properties.
Therefore, in this case, obviousness is not predicated on what was not
known at the time of invention.
Ans. 66. We find no misapplication of the principle of inherency.
Where ... 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.
In re Best, 562 F.2d 1252, 1255 (CCPA 1977) (emphasis added.) The
Examiner finds that,
the composition used in the method of the prior art as applied in
the rejection in the instant case is not structurally different from
the composition used in the claim method; it has exactly the
same active agent in the same amount and it has the same
species of buffer considered by Appellant to give rise to the
claimed functional properties, i.e., rapid uptake of nicotine.
Ans. 61. The Examiner properly shifted the burden of proof to Appellants to
show that the liquid nicotine compositions of Rose, Monte and Von
Wielligh, at the pH range of Tomar, would not possess the same craving
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control reduction as that of claim 35. Appellants did not provide appropriate
rebuttal evidence.
Appellants argue that Tomar teaches nicotine gums bound to ion
exchange resins and that the nicotine is not in free base form. App. Br. 14.
The Examiner responds, arguing that
Tamar [ sic, Tomar] generally teaches that nicotine absorption in
mucosal tissue is enhanced at higher pH, which clearly provides
motivation to increase the pH of any formulation used to deliver
nicotine to the oral mucosa as relied on in the rejection, not only for
gum formulations. Appellant has not provided any reasoning or
rationale for why the general teaching of Tamar [ sic, Tomar]
regarding pH sensitivity of nicotine delivery to the oral mucosa would
not motivate one of ordinary skill in the art at the time of invention to
adjust the pH of an oral spray formulation, which also delivers
nicotine to the oral mucosa .... The paragraph of Tamar [ sic, Tomar]
on page 223, left column, discussing the use of buffers in gums to
increase the pH explicitly concludes with "The experiments confirmed
that the pH of the oral environment, and not merely rinsing, can
control the absorption of nicotine through the oral mucosa." Given
this explicit statement (and the fact that the entire reference of Tamar
is about absorption of nicotine and not about release of nicotine from
a matrix), it is clear that Tamar [ sic, Tomar] is actually referring to
the use of buffers in the gum to increase salivary pH ("nicotine gum
buffered with sodium bicarbonate and bicarbonate to increase salivary
pH level" from the same paragraph of page 223, left column) to
enhance absorption across the oral mucosa, and not to release nicotine
from an exchange resin.
Ans. 45.
We find that the Examiner has the better argument, and agree with the
Examiner that one of ordinary skill in the art would read T omar to describe
the generic principle that the pH sensitivity of nicotine affects nicotine
absorption when delivered to the oral mucosa. This disclosure in Tomar
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provides motivation to one of ordinary skill in the art to buffer nicotine
administered to the oral mucosa.
Rejections 2 and 5
Rejections 2 and 5 as set forth in the grounds of rejection both apply
to claims 5 and 15. Appellants do not separately argue rejections 2 and 5 as
set forth in the grounds of rejection and they are summarily affirmed.
Written Description, Rejection 6
Claims 28, 29, 31, 32, 34, 36, 38, 40, and 47 are rejected under 35
U.S.C. § 112(a) or 35 U.S.C. 112 (pre-AIA), first paragraph, as failing to
comply with the written description requirement.
Appellants cancelled these claims in an amendment filed with the
Appeal Brief dated February 18, 2016. There is no indication that the
cancellation of these claims was entered by the Examiner, thus the pending
claims are those submitted Sept 22, 2014.
The Examiner finds that,
Claims 28, 31, 34, 36, and 38 recite the limitation of "about
20% at 2 minutes," which is not described in the specification or
original claims. Claims 29, 32, and 35 recite the limitation of
"between about 20% and about 50% at 2 minutes," which is not
described in the specification or original claims because "reduced by
50%" in paragraph 40 of the instant pecification and the 52.6%
reduction in craving in Figure 4 are single species, whereas the claims
recites a range starting at least about 20%, which is not disclosed as
described above, and thus increases the scope of the specification and
original claim.
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... Claim 40 recites "at least about 4 ng/ml between 5 and 60
minutes after administration," which is not described in the
specification or instant claims.
Ans. 4.
Appellants do not specifically respond to this rejection in the Appeal
Brief or Reply Brief, arguing that the claims have been cancelled. Reply Br.
3. However, the Examiner did not enter the cancellation of the claims. The
rejection of the cited claims for lack of written description is summarily
affirmed.
CONCLUSION OF LAW
The cited references support the Examiner's obviousness rejections,
which are affirmed for the reasons of record. The lack of written description
rejection is also affirmed. All pending, rejected claims fall.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(l )(iv).
AFFIRMED
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