Ex Parte Lindell et al

Patent Trials and Appeals Board

Jan 14, 2019

12619851 - (D) (P.T.A.B. Jan. 14, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
12/619,851 11/17/2009
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.
PUJ-0325/NICOLING
00732
CONFIRMATION NO.
9416
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 KATARINA E.A. LINDELL, BENGT A. BOSSON,
GUNNAR A. BERGENGREN, and ANETTE K. SCHLUTER
Appeal2017-004626 1
Application 11/619,851 2,
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 as being obvious under 35 U.S.C. § 103(a). We have jurisdiction
under 35 U.S.C. § 6(b ).
We affirm.
STATEMENT OF CASE
The following claim is representative.
1. A pharmaceutical composition, comprising:
1 Real Party in interest McNeil AB, Helsingborg. Sweden.
2 This application is related to United States applications 11/686,842
(Appeal No. 2017-001569), and 13/871,476 (Appeal No. 2017-004832).
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Application 12/619,851
nicotine in free base form present in a range of from
about 5 mg/ml to about 20 mg/ml of the composition,
calculated as nicotine free base;
at least 60% ( w /w) water; and
at least one buffer 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 a subject by from about 0.3 to about 4 pH units
per incidence of administration of 200 micro liters of the
composition,
the composition being in liquid form,
the composition having an alkaline pH, and
the composition adapted for administration to the oral cavity of
a subject by spraying, dropping, or pipetting to effect
transmucosal uptake of nicotine without chewing or sucking.
The remaining claims on appeal can be found in the Claims Appendix
to the Appeal Brief.
Cited References
Perno et al.,
Rose et al.,
Prencipe et al.,
Hussein et al.,
Jones U.S.
Monte
Von Wielligh
McCoy
U.S. 4,579,858
U.S. 4,920, 989
U.S. 5,000,944
us 5, 298,238
U.S. 5,656,255
U.S. 5,810,018
U.S. 6,024,097
WO 00/47203
2
Apr. 1, 1986
May 1, 1990
Mar. 19, 1991
Mar. 29, 1994
Aug. 12, 1997
Sept. 22, 1998
Feb. 15,2000
Aug. 17, 2000
Appeal2017-004626
Application 12/619,851
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).
Hyvonen et al., Fructose-Saccharin and Xylitol-Saccharin Synergism, J. OF
FOOD SCIENCE, Vol. 43, p. 251-254 (1978).
Grounds of Rejection
1. Claims 1--4, 6, 9, 10, 12-14, and 20-35 are rejected under
35 U.S.C. §103(a) as being unpatentable over Von Wielligh in
view of Tomar and Rose.
2. Claim 5 is rejected under 35 U.S.C. § 103(a) as being
unpatentable over Von Wielligh, Tomar, Rose and Hyvonen.
3. Claims 16 and 17 are rejected under 35 U.S.C. § 103(a) as being
unpatentable over Von Wielligh, Tomar, Rose and Jones.
4. Claims 9, 10, and 11 under 35 U.S.C. § 103(a) as being
unpatentable over Von Wielligh, Tomar, Rose and McCoy.
5. Claim 15 is rejected under 35 U.S.C. § 103(a) as being
unpatentable over Von Wielligh, Tomar, Rose, and Prencipe.
6. Claims 36 and 37 are rejected under 35 U.S.C. § 103(a) as being
unpatentable over Von Wielligh, Tomar, Rose and Hussein
7. Claims 1-4, 6, 12-14, 18, 19, and 23-35 are rejected under
35U.S.C. § 103(a) as being unpatentable over Monte, Tomar, Von
Wielligh, and Rose.
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8. Claim 5 is rejected under 35 U.S.C. § 103(a) as being
unpatentable over Monte, in view of Tomar, Von Weilligh, and
Hyvonen.
9. Claims 16 and 17 under 35 U.S.C. § 103(a) as being unpatentable
over Monte, in view of Tomar, Von Wiellligh, and Jones.
10. Claims 9, 10, and 20 are rejected under 35 U.S.C. §103(a) as
being unpatentable over Monte, Tomar, Von Wielligh and Rose.
11. Claims 9, 10, and 11 are rejected under 35 U.S.C. §103(a) as
being unpatentable over Monte, Tomar, Von Wielligh and
McCoy.
12. Claim 15 is rejected under 35 U.S.C. § 103(a) as being
unpatentable over Monte Monte, Tomar, Von Wielligh and
Prencipe.
13. Claim 31 is rejected under 35 U.S.C. § 112(b) or 35 U.S.C. § 112
(pre-AIA), second paragraph, as being indefinite for failing to
particularly point out and distinctly claim the subject matter which
the inventor or a joint inventor, or for pre-AIA the applicant,
regards as the invention.
FINDINGS OF FACT
The Examiner's findings of fact are set forth in the Answer at pages
2--42. The following facts are highlighted.
1. Rose teaches a method for delivering nicotine to a subject,
themethod 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
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Application 12/619,851
(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. Monte, 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. Rose, col. 14, 1. 28-30.
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
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comprising nicotine (col. 4, 1. 35) by spray administration to the oral cavity
(Von Wielligh, 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 therapy increases the pH of the oral
environment and thus facilitates the absorption of nicotine ("nicotine
replacement studies;" (Tomar, 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, col.
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. Hussein teaches that in oral sprays (column 1, line 9), it is
particularly useful to use deterpenated and fractionated flavor oils such as
deterpenated and fractionated peppermint oil ( column 2, lines 15-20) at
0.001 % to 5% (column 2, line 24). Final Act. 11.
13. Hyvonen teach that when combined together, xylitol and
saccharine provide a synergistic sweetening effect without the aftertaste
typical of saccharine (abstract). Final Act. 8.
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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, 5, 9, 15, 16, and 36, as representative claims for
purposes of this decision. Appellants do not present separate arguments for
each of the 13 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 purposes of
expediency and avoidance of redundancy in this Decision, Rejections 1-13,
as set forth in the grounds of rejection, are addressed together. Rejections
not argued are summarily affirmed. 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 an individual references will appear
separately, in specific paragraphs.
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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 was known in the art to adjust the pH of nicotine to
increase its absorption rate. Tomar, p. 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. Id.
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 ofF erno '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 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
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comment to the Examiner's argument set forth in the Final Rejection and
Answer.
We are not persuaded by Appellants' arguments that Jones and Perno
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. We find that 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 known to optimize the
result effective variable of pH to balance the nicotine absorption rate with
side effects associated with acidic pH. ("[D]iscovery of an optimum value of
a result effective variable in a known process is ordinarily within the skill of
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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,
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 would have been 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
cited only 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 buffer. Id. The Examiner responds, arguing that
Tamar [ sic, Tomar] generally teaches that nicotine absorption in
mucosal tissue is enhanced at higher pH, which clearly provides
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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. 39-40, 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. 41. 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. 19-20. We are not
persuaded by Appellants' argument. We find that the Examiner has
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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.
Appellants argue that the Examiner misinterprets the reference and
Appellants' disclosure, and misapplies the doctrine of inherency. App. Br.
19-20. 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. 20.
The Examiner responds, arguing that,
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] 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
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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. 61. We find no misapplication of the principle of inherency.
Where ... the claimed and prior art products are identical
orsubstantially 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 Von
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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 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. 39-40.
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We find that the Examiner has the better argument, and agree with the
Examiner that one of ordinary skill in the art would have read 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
Hyvonen, Hussein, Prencipe or McCoy cited references. 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 14 73, 14 7 4
(BPAI 2010) (Informative) ((emphasis added); and37 C.F.R. § 4I.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.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a). See 37 C.F.R.
§ 1.136(a)(l )(iv).
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AFFIRMED
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