Ex Parte Damaj et al

Patent Trial and Appeal Board

Oct 15, 2018

13991111 (P.T.A.B. Oct. 15, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
13/991,111 05/31/2013 Bassam B. Damaj
64046 7590 10/17/2018
Mintz Levin/San Diego Office
One Financial Center
Boston, MA 02111
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.
106150-0603 9047
EXAMINER
NEAGU, IRINA
ART UNIT PAPER NUMBER
1627
NOTIFICATION DATE DELIVERY MODE
10/17/2018 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):
IPDocketingBOS@mintz.com
IPFileroombos@mintz.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte BASSAM B. DAMAJ and RICHARD MARTIN
Appeal2017-001868
Application 13/991, 111 1
Technology Center 1600
Before DONALD E. ADAMS, ERIC B. GRIMES, and
RYAN H. FLAX, Administrative Patent Judges.
ADAMS, Administrative Patent Judge.
DECISION ON APPEAL
This Appeal under 35 U.S.C. § 134(a) involves claims 1--4, 6, 7, 20-
24, and 26-29 (App. Br. 1 and 4). 2 Examiner entered rejections under 35
U.S.C. § 103(a) and obviousness-type double patenting. We have
jurisdiction under 35 U.S.C. § 6(b ).
We AFFIRM.
1 Appellants identify "Nexmed (Holdings), Inc." as the real party in interest
(App. Br. 2).
2 The Appeal Brief is not paginated. Therefore, all references to page
numbers of the Appeal Brief refer to page numbers as if the Appeal Brief
was number consecutively beginning with the first page.
Appeal2017-001868
Application 13/991, 111
STATEMENT OF THE CASE
Appellants' disclosure "relates to enantiomers of dodecyl 2-(N,N-
dimethylamino )-propionate (DDAIP), and in particular the R-enantiomer
thereof' (Spec. 1: 4--5). Appellants' claim is representative and reproduced
below:
1. A dosage form comprising a pharmaceutically active
compound and 2R-dodecyl 2-(N,N-dimethylamino )-propionate
or a salt thereof, wherein the 2R-dodecyl 2-(N,N-
dimethylamino )-propionate has an enantiomeric purity of at
least about 70%, wherein the dosage form is a cream or a gel.
(App. Br. 9.)
The claims stand rejected as follows:
Claims 1--4, 6, 7, 20-24, and 26-29 stand rejected under 35 U.S.C.
§ 103(a) as unpatentable over the combination ofNovotny3 and
Buyuktimkin. 4
Claims 1, 6, and 7 stand rejected under the judicially created doctrine
of obviousness-type double patenting as being unpatentable over the claims
of Buyuktimkin in view of Novotny.
Claims 1--4, 6, 7, 20-24, and 26-29 stand rejected under the judicially
created doctrine of obviousness-type double patenting as being unpatentable
over the claims ofDamaj '625. 5
3 Jakub Novotny et al., Dimethylamino Acid Esters as Biodegradable and
Reversible Transdermal Permeation Enhancers: Effects of Linking Chain
Length, Chirality and Polyfluorination, 26 PHARMACEUTICAL RES. 811-21
(2009).
4 Biiyiiktimkin et al., US 6,118,020, issued Sept. 12, 2000.
5 Damaj et al., US 8,900,625 B2, issued Dec. 2, 2014.
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Application 13/991, 111
Claims 1--4, 6, 7, 20-24, and 26-29 stand rejected under the judicially
created doctrine of obviousness-type double patenting as being unpatentable
over the claims of Damaj '595 6 in view of Novotny.
Obviousness:
ISSUE
Does the preponderance of evidence relied upon by Examiner support
a conclusion of obviousness?
FACTUAL FINDINGS (FF)
We adopt Examiner's findings concerning the scope and content of
the prior art (Office Act. 7 5-7), and provide the following findings for
emphasis.
FF 1. Novotny discloses that a "[s]eries ofN,N-dimethylamino acid esters
was synthesized to study their transdermal permeation-enhancing potency,
biodegradability and reversibility of action. Effects of chirality, linking
chain length and polyfluorination were investigated" (Novotny, Abstract; see
Office Act. 5---6; Ans. 2-3; see also App. Br. 6; Reply Br. 7).
FF 2. Novotny discloses that"[ d]odecyl 2-( dimethylamino) propanoate
(DDAIP ... ) ... is a clinically used biodegradable transdermal permeation
enhancer" (Novotny 811 ( endnote omitted); see Office Act. 5---6; Ans. 2-3).
FF 3. Novotny discloses the R-enantiomer, S-enantiomer, and a racemic
mixture of dodecyl 2-( dimethylamino )propanoate (see Novotny 814 and
816; see Office Act. 5---6; Ans. 2-3 and 8; see also Reply Br. 7).
6 Damaj et al., US 8,962,595 B2, issued Feb. 24, 2015.
7 Office Action mailed July 16, 2015.
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Application 13/991, 111
FF 4. Novotny discloses that "[t]he effect of the linking chain length on the
enhancing activity of [] prepared compounds was evaluated using
theophylline as the model drug" and found "no significant difference
between the (R) and (S)-enantiomers [ofDDAIP] and [its] racemate"
(Novotny 816; see Office Act. 5-6; Office Act. 5 (Novotny "discloses
dosage forms comprising a pharmaceutically active compound (such as
theophylline ... ), and 2R-dodecyl 2-N,N-dimethylamino )propionate
(individual pure enantiomer ... ) ... as a transdermal permeability
enhancer"); Ans. 2-3 and 8; see also App. Br. 6; Reply Br. 8 (Novotny
"prepared a composition comprising theophylline and the R enantiomer of
DDAIP")).
FF 5. Novotny discloses that "the interaction of DDAIP with the skin
lipids and/ or the consequent barrier permeabilization is not dependent on the
exact spatial orientation of its polar head" (Novotny 817; see also App. Br.
6; Reply Br. 7).
FF 6. Novotny discloses that "[n]o stereoselectivity in action ofDDAIP
was found" (Novotny 820; see also App. Br. 6; Reply Br. 7).
FF 7. Examiner relies on Biiyiiktimkin to disclose "crystalline acid
addition salts of dodecyl 2-( dimethylamino )propanoate (DDAIP), such as
hydrochloric acid salt ... or organic salts such as acetic, benzoic, salicyclic,
lactic acid addition salts ... as skin penetration enhancers for a variety of
medicaments" ( Office Act. 6-7).
ANALYSIS
Appellants do not separately argue their claims. Therefore,
Appellants' claim 1, reproduced above, is representative. Appellants' claims
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Application 13/991, 111
2--4, 6, 7, 20-24, and 26-29 stand or fall with Appellants' claim 1. In re
Young, 927 F.2d 588, 590 (Fed. Cir. 1991).
The evidence of record supports a finding that Novotny discloses the
R-enantiomer, S-enantiomer, and racemate of DDAIP (see FF 2--4). Further,
there is no dispute on this record that Novotny discloses the 2R-dodecyl 2-
(N,N-dimethylamino )-propionate set forth in Appellants' claim 1.
There is also no dispute on this record that Novotny's 2R-dodecyl 2-(N,N-
dimethylamino )-propionate is at least about 70% enantiomerically pure as
required by Appellants' claim 1 (see FF 4). 8
The evidence of record supports a finding that Novotny discloses the
R-enantiomer, S-enantiomer, and racemate of DDAIP are equally effective
as penetration enhancers for a pharmaceutically active compound (FF 1---6).
Stated differently Novotny discloses that the R-enantiomer, S-enantiomer,
and racemate of DDAIP are equivalents (id.). "Express suggestion to
substitute one equivalent for another need not be present to render such
substitution obvious." In re Fout, 675 F.2d 297,301 (CCPA 1982); see also
In re Mayne, 104 F.3d 1339, 1340 (Fed. Cir. 1997) ("Because the applicants
merely substituted one element known in the art for a known equivalent, this
court affirms [the rejection for obviousness]"). Accord KSR Intern. Co. v.
Teleflex Inc., 550 U.S. 398, 416 (2007) ("when a patent claims a structure
already known in the prior art that is altered by the mere substitution of one
8 We recognize the separate arguments of Appellants' claims 20 and 29
presented in Appellants' Reply Brief (see Reply Br. 8). These arguments,
however, were not timely filed. See 37 C.F .R 41.41 (b )(2); see also Ex parte
Borden, 93 USPQ2d 1473, 1474 (BPAI 2010) (informative) (Appellant fails
to "explain what 'good cause' there might be to consider the new argument.
On this record, Appellant's new argument is belated.").
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Application 13/991, 111
element for another known in the field, the combination must do more than
yield a predictable result").
Thus, the evidence of record supports a finding that Novotny discloses
a dosage form comprising a pharmaceutically active compound and 2R-
dodecyl 2-(N,N-dimethylamino )-propionate, wherein the 2R-dodecyl 2-
(N,N-dimethylamino )-propionate has an enantiomeric purity of at least about
70% (see FF 1---6; cf App. Br. 9; see Reply Br. 8 (Novotny "prepared a
composition comprising theophylline and the R enantiomer of DDAIP")).
There is no dispute on this record that "creams or gels are [the] most
common formulations for drugs applied transdermally" (see Office Act. 7;
Ans. 4). Therefore, we find no error in Examiner's conclusion that, at the
time Appellants' invention was made, it would have been prima facie
"obvious to a person of ordinary skill in the art to prepare a dosage form
such as a cream or a gel comprising a pharmaceutically active compound
and 2R-dodecyl 2-(N,N-dimethylamino)propionate" (Office Act. 7; Ans. 4).
Appellants recognize that Novotny discloses the R-enantiomer, S-
enantiomer, and racemate of DDAIP are equally effective as penetration
enhancers for a pharmaceutically active compound (App. Br. 5-6; Reply Br.
7; see FF 1---6). Nonetheless, Appellants assert that Novotny "cannot be
properly used as a reference because it teaches away from the claimed
composition" (App. Br. 6; see also id. at 7 ("what is missing from the
Office's comments is the very rationale that lies at the heart of Applicant's
[sic] rebuttal: the teaching away o(Novotny [sic]. Based on Novotny [sic],
it is apparent that it teaches away from the claimed invention")). The basis
for Appellants' contention that Novotny teaches away from the dosage form
set forth in Appellants' claim 1 is that Novotny provided "no reason to select
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Appeal2017-001868
Application 13/991, 111
R DDAIP as a penetration enhancer over either the S-enantiomer ofDDAIP
or racemic DDAIP" (Reply Br. 8). In this regard, Appellants contend that
"absent hindsight reconstruction, how could a skilled artisan use Novotny
[sic] to guide her to arrive at the claimed composition[]? According to
Appellants, Novotny "would not have led a person of ordinary skill in the art
to modify Novotny's [sic] compositions while excluding S-DDAIP and
retainingR-DDAIP in it" (Reply Br. 9). We are not persuaded.
A reference is said to "teach away" from a claimed invention when it
"suggests that the line of development flowing from the reference's
disclosure is unlikely to be productive of the result sought by the applicant"
(In re Gurley, 27 F.3d 551, 553 (Fed. Cir. 1994)). On this record, rather
than teaching away from the subject matter of Appellants' claim 1, Novotny
discloses that the R-enantiomer, S-enantiomer, and racemate of DDAIP are
equally effective as penetration enhancers for a pharmaceutically active
compound. In addition, as Appellants recognize, Novotny expressly
discloses the preparation of "a composition comprising theophylline and the
R enantiomer of DDAIP" (Reply Br. 8). Therefore, we are not persuaded by
Appellants' contentions regarding hindsight reconstruction.
Because Examiner relied upon Biiyiiktimkin to disclose subject matter
not present in Appellants' claim 1 and not argued by Appellants, we do not
address Biiyiiktimkin in the foregoing analysis. In affirming an obviousness
rejection, the Board may rely upon less than all the references cited by
Examiner. See In re Kronig, 539 F.2d 1300, 1302 (CCPA 1976).
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Application 13/991, 111
CONCLUSION
The preponderance of evidence relied upon by Examiner supports a
conclusion of obviousness. The rejection of claim 1 under 35 U.S.C.
§ 103(a) as unpatentable over the combination of Novotny and Biiyiiktimkin
is affirmed. Claims 2--4, 6, 7, 20-24, and 26-29 are not separately argued
and fall with claim 1.
Obviousness-type Double Patenting:
ISSUE
Does the preponderance of evidence relied upon by Examiner support
a conclusion of obviousness-type double patenting?
ANALYSIS
The obviousness-type double patenting rejection over the claims of
Buyuktimkin in view of Novotny:
Biiyiiktimkin's claim 1 reads: "A crystalline salt of dodecyl 2-(N,N-
dimethylamino )-propionate" (Biiyiiktimkin 6: 44--45; see Office Act. 9
("Claims 1-6 and 8 of [Biiyiiktimkin] are drawn to a crystalline salt of
racemic DDAIP")). Examiner relies on Novotny to teach "DDAIP, its R-
enantiomer, and its HCl salt, as penetration enhancers" (Office Act. 9).
Therefore, based on the combination of the claims of Biiyiiktimkin in
view of Novotny, Examiner concludes that, at the time Appellants' invention
was made, it would have been prima facie obvious "to synthesize an acid
addition salt of 2R-dodecyl 2-(N,N-dimethylamino) propionate and use it as
[a] penetration enhancer in a composition comprising a pharmaceutically
active compound ... with the expectation that the resulting salt will retain
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Application 13/991, 111
the penetration enhancing properties of the R-enantiomer of DDAIP" (Office
Act. 10; see Ans. 6).
Appellants contend that "[fJor at least the reasons discussed above[,
with respect to the rejection under 35 U.S.C. § 103(a)], this rejection, in
view ofNovotny [sic] can also not be sustained" (App. Br. 8; see id. at 6
(with respect to the rejection under 35 U.S.C. § 103(a), Appellants contend
that "Buyuktimkin is silent about separated DDAIP enantiomers and their
properties" and "[t]herefore, it does not cure the deficiencies ofNovotny
[sic]"); see also Reply Br. 10-11).
For the reasons set forth above, and by Examiner, we are not
persuaded by Appellants' contentions.
The obviousness-type double patenting rejection over the claims of Dama}
'595 in view of Novotny:
Damaj '595's claims 1, 10 and 11 are reproduced below:
1. An oral or subctutaneously injectable composition consisting
of a small molecule therapeutic, an alkyl N,N-disubstituted-
amino acetate, and one or more pharmaceutically acceptable
earners.
(Damaj '595 12: 49-52.)
10. The composition in accordance with claim 1 wherein the
alkyl N,N-disubstituted-amino acetate is dodecyl 2-(N,N-
dimethylamino) propionate.
(Damaj '595 13: 9-11.)
11. The composition in accordance with claim 1 wherein the
alkyl N,N-disubstitutted-amino acetate is dodecyl 2-(N,N-
dimethylamino) propionate hydrochloride.
(Damaj '595 13: 12-14.)
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Application 13/991, 111
Examiner finds that Damaj '595 claims "an oral or subcutaneously
injectable composition comprising a small molecule therapeutic and an alkyl
N,N-disubstituted-amino acetate; the genus of alkyl N,N-disubstituted-
amino acetates encompasses DDAIP, or a salt thereof ( claims 10 and 20
recite DDAIP, claims 11 and 21 recite DDAIP hydrochloride)" (Ans. 7; see
Office Act. 11). Examiner further finds that Novotny "teaches DDAIP, its
R-enantiomer, and its HCl salt, as ingredients in compositions comprising
small molecule therapeutics" (Ans. 7; see Office Act. 11 ).
Therefore, based on the combination of the claims of Damaj '595 in
view of Novotny, Examiner concludes that, at the time Appellants' invention
was made, it would have been prima facie obvious "to replace DDAIP with
the R-enantiomer of DDAIP, or salt thereof, in a composition comprising a
small molecule therapeutic taught by claims 1-29 of [Damaj '595], with the
expectation that the resulting composition will retain therapeutic properties"
( Ans. 7; see Office Act. 11 ). In this regard, Examiner further reasons that "it
would have been obvious for a person of ordinary skill in the art to prepare a
cream or a gel as a dosage form of such a composition, because creams and
gels are physical forms most commonly used in drug formulations" (Ans. 7;
see Office Action 11 ).
Appellants contend that "[ fJor at least the reasons discussed above,
[with respect to the rejection under 35 U.S.C. § 103,] this rejection, in view
of Novotny [sic] can also not be sustained" (App. Br. 8; see also Reply Br.
11 ). For the reasons set forth above, and by Examiner, we are not persuaded
by Appellants' contentions.
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Application 13/991, 111
The obviousness-type double patenting rejections over the claims of Dama}
'625:
Damaj '625's claims 28, 29, and 32 are reproduced below:
28. A composition comprising the compound of Formula I:
V->''' ,, K'·······11 (}~
X
J)>""'''"' ')'' ·~ K
where n is an integer from 6-12 inclusive; R1, and R2, are the
same or different and are selected independently from the
group consisting of H, substituted or unsubstituted, straight or
branched chain C1-C10 alkyl, CH3, CHOHCH3, CH(CH3)2,
CH2C6H6, and CH2CH(CH3)2; R3, and R4, are the same or
different and are selected independently from the group
consisting of H, substituted or unsubstituted, straight or
branched chain C1-C10 alkyl, C6-C10 aryl or C6-C10 heteroaryl,
CH3, CH(CH3)2, CH2CH20H, CH2CH(CH3)2, and
(CH2)2N(CH2CH3)2, wherein if one of R3 and R4 is selected
from H, unsubstituted, straight or branched chain C1-C10 alkyl,
CH3, CH(CH3)2, and CH2CH(CH3)2, the other is selected from
substituted straight or branched chain C1-C10 alkyl, C6-C10 aryl
or C6-C10 heteroaryl, CH2CH20H, and (CH2)2N(CH2CH3)2;
R5, and R 6, are the same or different and are selected
independently from the group consisting of H and CH3, and
pharmaceutically acceptable salts thereof; and
a pharmaceutically acceptable excipient.
(Damaj '625 90: 26-55 (emphasis added).)
29. The composition of claim 28 further comprising an active
pharmaceutical ingredient.
(Damaj '625 90: 56-57.)
32. The composition of claim 28 wherein the composition is
provided in an unit dosage form.
(Damaj '625 90: 63--64.)
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Application 13/991, 111
Examiner finds that Damaj '625 's
[ c ]laims 2 8-3 5 ... are drawn to a composition comprising an
active pharmaceutical ingredient and a compound of formula (I)
such as DDAIP (which is a compound of formula I wherein R 1
= H R2 = methyl R3 = R4 = methyl R5 = R6 = H n = 10) its
' ' ' ' ' enantiomers (the Specification (column 3, lines 52-54) indicates
that the genus of compounds of formula I includes D and L-
enantiomers of DDAIP), or salts thereof).
(Ans. 6; see Office Act. 10.) In this regard, we note that a C1 alkyl, i.e., the
smallest alkyl, is methyl (CH3-).
Therefore, based on the claims of Damaj '625, Examiner concludes
that, at the time Appellants' invention was made,
[i]t would have been prima facie obvious to prepare a
cream or a gel as a dosage form of a composition comprising a
pharmaceutically active compound and 2R-dodecyl 2-(N,N-
dimethylamino) propionate, because such a composition, albeit
in the dosage form of a table, capsule, granule, powder,
solution, suspension, spray drop ... is encompassed by the
genus of claims 28-35 of [Damaj '625].
(Ans. 6-7; Office Act. 10-11.)
Appellants contend that "[t]he cited claims of [Damaj '625] do[] not
teach or suggest the claimed compositions containing R-enantiomercally
[sic] enriched DDAIP" (App. Br. 8). For the reasons set forth above, and by
Examiner, we are not persuaded. To be complete, we recognize Appellants'
reproduction of Damaj '625 's claim 28 and, re-emphasize that Damaj '625 's
claim 28, as interpreted by Examiner, wherein, inter alia, "R3 = R4 =
methyl" reads on DDAIP (see Ans. 6; see Office Act. 1 O; see also App. Br.
8; Reply Br. 11 ).
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Application 13/991, 111
CONCLUSION
The preponderance of evidence relied upon by Examiner supports a
conclusion of obviousness-type double patenting.
The rejection of claim 1 under the judicially created doctrine of
obviousness-type double patenting as being unpatentable over the claims of
Biiyiiktimkin in view of Novotny is affirmed. Claims 6 and 7 are not
separately argued and fall with claim 1.
The rejection of claim 1 under the judicially created doctrine of
obviousness-type double patenting as being unpatentable over the claims of
Damaj '595 in view of Novotny is affirmed. Claims 2--4, 6, 7, 20-24, and
26-29 are not separately argued and fall with claim 1.
The rejection of claim 1 under the judicially created doctrine of
obviousness-type double patenting as being unpatentable over the claims of
Damaj '625 is affirmed. Claims 2--4, 6, 7, 20-24, and 26-29 are not
separately argued and fall with claim 1.
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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