Ex Parte Lindell et al

Patent Trial and Appeal Board

Jan 14, 2019

13871476 (P.T.A.B. Jan. 14, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
13/871,476 04/26/2013
23377 7590 01/16/2019
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.
103669.000329 6756
EXAMINER
THAKOR, DEV ANG K
ART UNIT PAPER NUMBER
1619
NOTIFICATION DATE DELIVERY MODE
01/16/2019 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):
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, ANETTE K. SCHLUTER,
GUNNAR A. BERGENGREN,
and BENGT A. BOSSON
Appeal2017-004832
Application 13/871,47612
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(a). The Examiner has rejected
The pending claims for obviousness. We have jurisdiction under 35 U.S.C.
§ 6(b).
We affirm.
1 This application is related to United States applications 11/686,842
(Appeal 2017-001569) and 12/619 ,851.
2 According to Appellants, the Real Party in Interest is McNeil AB of
Helsingborg, Sweden.
Appeal2017-004832
Application 13/871,476
STATEMENT OF CASE
The following claim is representative.
1. A liquid pharmaceutical formulation for use in the
treatment of addiction to tobacco or nicotine, comprising:
(i) nicotine in free nicotine base form; and
(ii) a buffering agent,
(iii) the liquid pharmaceutical formulation being adapted
for administration to the oral cavity of a subject by spraying,
dropping or pipetting, and
(iv) the liquid pharmaceutical formulation being adapted
so as to achieve a tmax of nicotine in venous blood of the
subject within from about 3 to about 20 minutes after an
incidence of administration of 200 micro liters of the liquid
pharmaceutical formulation.
Additional claims on appeal are found in the Claims Appendix to the Appeal
Brief.
Cited References
Perno et al.
(hereinafter "Perno")
Rose et al.
(hereinafter "Rose")
Prencipe et al.
(hereinafter "Prencipe")
Jones
Monte
Von Wielligh
U.S. 4,579,858
U.S. 4,920, 989
U.S. 5,000,944
U.S. 5,656,255
U.S. 5,810,018
U.S. 6,024,097
2
Apr. 1, 1986
May 1, 1990
Mar. 19, 1991
Aug. 12, 1997
Sept. 22, 1998
Feb. 15,2000
Appeal2017-004832
Application 13/871,476
McCoy et al. WO 00/4 7203
(hereinafter "McCoy")
Aug. 17, 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). (Hereinafter "Harris").
Tomar et al., Review of the Evidence that pH is a Determinant of
Nicotine Dosage from Oral Use of Smokeless Tobacco, TOBACCO
CONTROL 6:219-225 (1997). (Hereinafter "Tomar").
Richard A. Frazier et al., Development of a Capillary Electrophoresis
Method for the Simultaneous Analysis of Artificial Sweeteners, Preservatives
and Colours in Soft Drinks, JOURNAL OF CHROMATOGRAPHY A, 87 6,
213-220 (2000). (Hereinafter "Frazier").
Grounds of Rejection
1. Claims 1-3, 5-8, 10, 11, 12, 13, and 15-18 are rejected under 35
U.S.C. §103(a) as being unpatentable over Von Wielligh in view
of Rose and Tomar.
2. Claim 4 is rejected under 35 U.S.C. § 103(a) as being unpatentable
over Von Wielligh in view of Rose, Tomar, and Prencipe.
3. Claim 9 is rejected under 35 U.S.C. § 103(a) as being unpatentable
over Von Wielligh in view of Rose, Tomar, and Jones.
4. Claim 12 is rejected under 35 U.S.C. § 103(a) as being
unpatentable over Von Wielligh in view of Rose, Tomar, McCoy,
Monte, and Frazier.
5. Claims 1-3, 5, 7-10, 12, 13, 17, and 18 are rejected under 35
U.S.C. § 103(a) as being unpatentable over Monte and Tomar.
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Application 13/871,476
6. Claim 4 is rejected under 35 U.S.C. § 103(a) as being unpatentable
over Monte in view of Tomar and Prencipe.
7. Claims 6 and 11 are rejected under 35 U.S.C. § 103(a) as being
unpatentable over Monte in view of Tomar, and Rose.
8. Claims 15 and 16 are rejected under 35 U.S.C. §103(a) as being
unpatentable over Monte in view of Tomar, and Von Wielligh.
9. Claim 12 is rejected under 35 U.S.C. §103(a) as being
unpatentable over Monte, Tomar, McCoy, and Frazier.
10. Claims 1-3, 6, 7, 8, 10, 12, 11, 13, and 17-19 are rejected under
35 U.S.C. §103(a) as being unpatentable over in view ofTomar.
11. Claim 4 is rejected under 35 U.S.C. § 103(a) as being unpatentable
over Rose, Tomar, and Prencipe.
12. Claim 5 is rejected under 35 U.S.C. § 103(a) as being unpatentable
over Rose, Tomar, and Monte.
13. Claim 9 is rejected under 35 U.S.C. § 103(a) as being unpatentable
over Rose, Tomar, and Jones.
14. Claim 12 is rejected under 35 U.S.C. § 103(a) as being
unpatentable over Rose, Tomar, Monte, Frazier, and McCoy.
FINDINGS OF FACT
The Examiner's findings of fact are set forth in the Answer at pages
2--43. 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
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Application 13/871,476
spraying, i.e., via oral transmucosal delivery without chewing or sucking
(Rose, 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 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. (Monte, 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. Id. at Col. 3, 11. 50-60; Ans. 20.
4. Rose teaches that for a concentration range similar to that of Monte (i.e.,
0.01 o/o-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. Id. at Col. 14, 11. 28-30.
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6. Monte teaches nicotine in free base form. Monte, 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 (Von Wielligh, col. 4, 1. 35) by spray.
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 therapy increases the pH of
the oral environment and thus facilitates the absorption of nicotine
(Tomar, "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 (id., "human studies," page 222, left
column).
9. Prencipe teaches that sodium hydroxide is useful to adjust the pH of a
solution for oral use to 8.5, i.e., to an alkaline condition (Prencipe,
column 9, lines 43-44).
10. McCoy teaches that poloxamers enhance the oral absorption of
pharmaceutical agents by modifying the surface membrane of the oral
mucosa (McCoy, abstract).
11. The oral formulation of McCoy "contains the surfactant at 0.1 % to 20%
by weight (McCoy, page 7, lines 24-24) and 0.12% sweetener (i.e., about
0.2% .... )." Final Act. 11.
12. Frazier teaches that the most commonly used artificial sweeteners in soft
drinks (i.e., oral compositions) are aspartame, acesulfame k, and
saccharin. Frazier, 214, left column.
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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)).
Obviousness Rejection
We select claims 1, 4, 5, 6, 9, 12, and 15, as representative claims for
purposes of this decision. Appellants do not present separate arguments for
each of the 14 grounds of rejection listed above, in the Brief, rather,
Appellants appear to group all rejections together in the Appeal Brief and
present group arguments that apply to all of the rejections. For expediency
and avoidance of redundancy in this Decision, Rejections 1-14, as set forth
in the grounds of rejection, are combined, and addressed below. Arguments
not shared by all of the rejections, or arguments with respect to individual
references will appear separately, in specific paragraphs. Arguments not
made are waived. See 37 C.F.R. § 4I.37(c)(iv).
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Essentially, Rose, Monte, and Von Wielligh teach liquid formulations
of nicotine. FF 1, 2, and 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 was known in the art to adjust the pH of
nicotine to increase its absorption rate. Tomar 222, col. 1.
Appellants contend that the prior art of Jones and Perno teaches away
from the claimed invention. App. Br. 9--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 Perno is limited to nasal administration and that side effects
of administration of Ferno's composition 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 before us is: Does the evidence of record teach
away from the claimed invention?
ANALYSIS
We agree with, and adopt, the Examiner's fact findings, statement of
the rejection and responses to Appellants' arguments as set forth in the
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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. See In re De Blauwe, 736 F.2d 699, 705
(Fed. Cir. 1984) (Arguments and conclusions unsupported by factual
evidence carry no evidentiary weight). 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 have readily recognized under
scientific pH principles that more buffering of nicotine would decrease the
acidity of nicotine in a formulation, as well alter some of the side effects
associated with acidic formulations of nicotine. Moreover, one of ordinary
skill in the art would have optimized the result effective variable of pH to
balance the nicotine absorption rate with side effects associated with acidic
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pH. ("[D]iscovery of 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).
Therefore, the motivating benefit of increased nicotine absorption at a higher
pH would tend to reduce side effects associated with acidic formulations like
those of Jones and Perno. The benefit of increased nicotine absorption
would have been 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 15, 2015, p. 22, 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. Final Act. 22-24, 33. 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 buffer. 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 ...
Final Act. 30, et. seq.; Tomar, p. 222, col. 1.
T omar 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. 40.
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
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(BP AI 2011) in support of this proposition. App. Br. 19--20. We are not
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 F emo is insufficient to show side effects in the oral
cavity at the buffered pH range suggested by Tomar.
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. 19.
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
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provided by Tamar [sic, Tomar] 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.
Ans. 55.
Therefore, in this case, obviousness is not predicated on what was not
known at the time of invention. 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. 55-56. The Examiner properly shifted the burden of proof to
Appellants to show that the liquid nicotine compositions of Rose, Monte and
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Von Wielligh, at the pH range of Tomar, would not possess the same
craving 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. 13.
The Examiner response, 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 [sic] 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. 40.
We find that the Examiner has the better argument, and agree
with the Examiner that one of ordinary skill in the art would read
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Tomar to describe the generic principle that the pH sensitivity of
nicotine affects nicotine absorption when delivered to the oral
mucosa. This disclosure in Tomar provides motivation to one of
ordinary skill in the art to buffer nicotine administered to the oral
mucosa.
Appellants' Brief provides no comment or analysis of the
Frazier, Prencipe, or McCoy cited references, or of the separate 14 rejections
as set forth in the grounds of rejection. Unargued rejections are summarily
affirmed. Furthermore, "[T]he reply brief [is not] an opportunity to make
arguments that could have been made in the principal brief on appeal to
rebut the Examiner's rejections, but were not"); see also 37 C.F.R.
§ 4I.67(c)(vii) ("Any arguments or authorities not included in the [Appeal]
brief ... will be refused consideration by the Board"), see Ex parte Borden,
93 USPQ2d 1473, 1474 (BPAI 2010) (Informative) ((emphasis added); and
3 7 C.F .R. § 41.41 (b) (A reply brief shall not include any new or non-
admitted amendment, or any new or non-admitted affidavit or other
Evidence) (emphasis added). Arguments not made are waived.
CONCLUSION OF LAW
The cited references support the Examiner's obviousness rejections,
which are affirmed for the reasons of record. All pending, rejected claims
fall.
AFFIRMED
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