Ex Parte Bohlin et al

Patent Trials and Appeals Board

Jun 12, 2019

13916754 - (D) (P.T.A.B. Jun. 12, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO.
13/916,754
106224 7590
White & Case LLP
FILING DATE
06/13/2013
06/14/2019
701 13th Street NW
Washington, DC 20005
FIRST NAMED INVENTOR
Martin Hans Bohlin
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.
1848081-0002-048-101 2562
EXAMINER
CARTER, KENDRA D
ART UNIT PAPER NUMBER
1627
NOTIFICATION DATE DELIVERY MODE
06/14/2019 ELECTRONIC
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
following e-mail address(es):
wcpatents@whitecase.com
sherry. beckham@whitecase.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte MARTIN HANS BORLIN and CRAIG ROBERT STEWART
Appeal2017-011069 1
Application 13/916,754
Technology Center 1600
Before FRANCISCO C. PRATS, JOHN E. SCHNEIDER, and
RACHEL H. TOWNSEND, Administrative Patent Judges.
PRATS, Administrative Patent Judge.
DECISION ON APPEAL
This appeal under 35 U.S.C. § 134(a) involves claims to a
pharmaceutical salt of a compound useful for treating pathologies such as
Alzheimer's disease. The Examiner entered eight rejections for
obviousness-type double patenting.
We have jurisdiction under 35 U.S.C. § 6(b).
We affirm six of the rejections, and reverse the other two.
1 Appellants identify AstraZeneca AB, as the real party in interest in this
appeal. Appeal Br. 2. Appellants state that "Eli Lilly and Company, with
offices at Lilly Corporate Center, Indianapolis, IN 46285, USA, has agreed
with AstraZeneca to jointly develop and commercialize molecules that fall
within the scope of the present patent application." Id.
Appeal2017-011069
Application 13/916,754
STATEMENT OF THE CASE
The following grounds of rejection are before us for review:
( 1) Claim 1, on the ground of nonstatutory double patenting over
claim I of the '483 patent2 and Cacatian3 (Ans. 2-3);
(2) Claims 2, 3, and 14, on the ground of nonstatutory double
patenting over claim 1 of the '483 patent, Cacatian, Berge, 4 and Foumet5
(Ans. 3-5); 6
(3) Claim 1, on the ground of nonstatutory double patenting over
claims 1 and 9 of the '911 patent7 and Cacatian (Ans. 5-7);
(4) Claim 14, on the ground of nonstatutory double patenting over
claims 1 and 9 of the '911 patent, Cacatian, Berge, and Fournet (Ans. 7-8);
( 5) Claim 1, on the ground of nonstatutory double patenting over
claims 1-13 of the '183 patent8 and Cacatian (Ans. 8-10);
2 US 8,415,483 B2 (issued Apr. 9, 2013).
3 WO 2010/105179 A2 (published Sept. 16, 2010).
4 Stephen M. Berge et al., Pharmaceutical Salts, 66 J. PHARM. SCI. 1-19
(1977).
5 US 2011/0144154 Al (published June 16, 2011).
6 In restating the rejection based on the combination of claim 1 of the '483
patent, Cacatian, Berge, and F oumet, the Examiner includes a discussion
explaining why the features recited in Appellants' claims 2 and 3 would
have been obvious over the cited combination of references. See Ans. 4--5.
Therefore, although the initial list of claims subject to that rejection does not
include claims 2 and 3, we presume the Examiner intended to include claims
2 and 3 in the rejection. We note, however, that none of the other rejections
restated in the Examiner's Answer includes or discusses claims 2 and 3 (see
Ans. 5-15), whereas the corresponding rejections in the Final Action, from
which this appeal is taken, all include and discuss claims 2 and 3 (see Final
Act. 9-11, 13-18).
7 US 8,865,911 B2 (published Oct. 21, 2014).
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(6) Claim 14, on the ground of nonstatutory double patenting over
claims 1-13 of the '183 patent, Cacatian, Berge, and Fournet (Ans. 10-12);
(7) Claim 1, on the ground of nonstatutory double patenting over
claims 1-16 of the '129 patent9 and Cacatian (Ans. 12-13); and
(8) Claim 14, on the ground of nonstatutory double patenting over
claims 1-16 of the' 129 patent, Cacatian, Berge, and Fournet (Ans. 13-15).
Claims 1 and 14 illustrate the appealed subject matter at issue and
read as follows:
1. A camsylate salt of (lr,l'R,4R)-4-methoxy-5' '-methyl-
6' -[5-(prop-1-yn-1-yl)pyridin-3-yl]-3 'H-dispiro[cyclohexane-
1,2' -indene-1 ',2' '-imidazol]-4' '-amine:
0
II Ho~s
II
0
14. A crystalline camsylate salt of (lr,l'R,4R)-4-methoxy-
5' '-methyl-6' -[5-(prop-1-yn-1-yl)pyridin-3-yl]-3 'H-
dispiro[ cyclohexane-1,2' -indene-1 ',2' '-imidazol]-4' '-amine:
8 US 9,000,183 B2 (issued Apr. 7, 2015).
9 US 9,248,129 B2 (issued Feb. 2, 2016).
3
"1110
\
0
Ho-M
II
0
Appeal2017-011069
Application 13/916,754
Appeal Br. 25, 28.
STANDARD OF REVIEW
As stated inJn re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992):
[T]he examiner bears the initial burden ... of presenting a
primafacie case ofunpatentability ....
After evidence or argument is submitted by the applicant
in response, patentability is determined on the totality of the
record, by a preponderance of evidence with due consideration
to persuasiveness of argument.
DOUBLE PATENTING-THE '483 PATENT
The Examiner's Prima Facie Case
In rejecting Appellants' claim 1 over claim 1 of the '483 patent and
Cacatian, the Examiner cited claim 1 of the '483 patent as reciting a
pharmaceutically acceptable salt of the same parent compound as recited in
Appellants' claim 1, and noted that the specification of the '483 patent
included non-toxic salts formed from organic acids among pharmaceutically
acceptable salts. Ans. 2-3.
The Examiner conceded that claim 1 of the '483 patent differed from
Appellants' claim 1 in that claim 1 of the '483 patent did not specifically
recite the camsylate ( camphorsulfonic acid) salt of the claimed compound.
Id. at 3. The Examiner cited Cacatian as evidence that camsylate was known
in the art to form pharmaceutically acceptable salts with therapeutic
compounds, and that it therefore would have been obvious to form the
camsylate salt of the parent compound recited in claim 1 of the '483 patent,
and thereby produce the camsylate salt recited in Appellants' claim 1. See
id.
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In rejecting Appellants' claims 2, 3, and 14 over claim 1 of the '483
patent, Cacatian, Berge, and Fournet, the Examiner reasoned that a skilled
artisan "would find it obvious and motivated to make the crystalline
camsylate salt of the claimed [parent] compound because '483 teach[ es]
pharmaceutical acceptable salts of the claimed compounds, in which
camsylate is a known pharmaceutical salt as taught by Cacatian et al." Id. at
4.
The Examiner reasoned that the crystalline form of the camsylate salt
recited in Appellants' claim 14 would have been obvious in view of Berge's
teachings regarding the selection criteria for salt selection, which include
ease of crystallization. See id. (noting that "FDA-Approved commercially
marketed salts include camsylate, for example (see table 1 [of Berge])").
The Examiner also noted that the "crystalline form of the salt of a compound
can help facilitate [its] implementation in the manufacture of pharmaceutical
compositions and be used to obtain the X-ray diffraction profile as
demonstrated by Fournet et al." Id. at 4--5.
The Examiner further reasoned that, "[w]ith regard to the X-ray
diffraction powder diffraction patterns taught in claims 2 and 3, these are
obvious properties of the crystalline compound. Since '483 obviously
teaches the claimed crystalline compound, upon taking the X-ray of the
compound the properties of the compound would be the same." Id. at 5
(citing In re Best, 562 F.2d 1252, 1254 (CCPA 1977)).
Analysis-Claim 1
Having carefully considered all of the arguments and evidence
advanced by Appellants and the Examiner, we find that the preponderance
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of the evidence supports the Examiner's conclusion that the salt compound
recited in Appellants' claim 1 would have been obvious in view of claim 1
of the '483 patent and Cacatian.
Appellants' claim 1 recites a camsylate salt of (lr,l'R,4R)-4-methoxy-
5' '-methyl-6' -[5-(prop-1-yn-1-yl)pyridin-3-yl]-3 'H-dispiro[ cyclohexane-
1,2' -indene-1 ',2" -imidazol]-4" -amine. Appeal Br. 25.
Claim 1 of the '483 patent recites, "[a] compound which is
(lr,l'R,4R)-4-methoxy-5' '-methyl-6' -[5-(prop-1-yn-1-yl)pyridin-3-yl]-3 'H-
dispiro[ cyclohexane-1,2' -indene-1 ',2 "-imidazol]-4" -amine or a
pharmaceutically acceptable salt thereof" The '483 patent, 216: 13-16
( emphasis added).
Appellants' claim 1 thus differs from claim 1 of the '483 patent only
in that Appellants' claim 1 recites a specific salt of the claimed parent
compound, the camsylate salt, whereas claim 1 of the '483 patent recites any
pharmaceutical salt of the same parent compound.
As the Examiner pointed out, however, the '483 patent defines
"pharmaceutically acceptable salts" as "derivatives of the disclosed
compounds wherein the parent compound is modified by making acid or
base salts thereof' with examples including "organic acid salts of basic
residues such as amines; alkali or organic salts of acidic residues such as
carboxylic acids; and the like." Id. at 15:22-31.
As the Examiner also pointed out, similar to the '483 patent, Cacatian
defines pharmaceutically acceptable salts as including organic acid salts of
its disclosed parent compounds, and includes the camsylate salt among a list
of about 79 other pharmaceutically acceptable salts useful for combination
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with its parent compounds. Cacatian 54--55 (citing Berge 1-19). We note,
moreover, that the parent compounds disclosed in Cacatian have a three-ring
core structure similar to the structure of the compound recited in claim 1 of
the '483 patent. Compare Cacatian 28 ( compounds II and IV) to the '483
patent, 100:35--45 (structural formula of compound recited in claim 1 of the
'483 patent).
As the Supreme Court explained in KSR Int 'l Co. v. Teleflex Inc., 550
U.S. 398 (2007), solving a problem by selecting a solution from a limited
number of known options is obvious:
When there is a design need or market pressure to solve a
problem and there are a finite number of identified, predictable
solutions, a person of ordinary skill has good reason to pursue
the known options within his or her technical grasp. If this
leads to the anticipated success, it is likely the product not of
innovation but of ordinary skill and common sense. In that
instance the fact that a combination was obvious to try might
show that it was obvious under § 103.
Id. at 421.
In the present case, given Cacatian's teaching that camsylate was one
of a limited number of known pharmaceutically acceptable salt-forming
organic acids useful with its parent compounds, we agree with the Examiner
that a skilled artisan had a good reason for, and a reasonable expectation of
success in, preparing the camsylate salt of other therapeutic compounds
having a similar chemical structure and similar utility, including the parent
compound recited in claim 1 of the '483 patent. We therefore also agree
with the Examiner that, when preparing the expressly recited
pharmaceutically acceptable salt of the parent compound of claim 1 of the
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'483 patent, the skilled artisan would have considered the camsylate salt
recited in Appellants' claim 1 to be obvious.
We acknowledge the general rule, identified by Appellants (see
Appeal Br. 7-8; Reply Br. 2-3), that "an earlier patent's specification is not
available to show obviousness-type double patenting." Sun Pharmaceutical
Industries, Ltd. v. Eli Lilly and Co., 611 F.3d 1381, 1387 (Fed. Cir. 2010).
As explained in Sun, however, an exception to that general rule exists
in that, "where [ as here] a patent features a claim directed to a compound,
the court must consider the specification because the disclosed uses of the
compound affect the scope of the claim for obviousness-type double
patenting purposes." Id. (emphasis added). In particular, "[i]n examining
the specification of the earlier patent, the court must consider the
compound's disclosed utility." Id. (emphasis added; internal quotes and
citation omitted).
In the present case, the '483 patent discloses that the parent compound
recited in its claim 1 has utility as an "inhibitor[] of B-secretase and hence
inhibit[s] the formation of amyloid B (AB) peptides and will be used for
treatment and/or prevention of AB -related pathologies such as Alzheimer's
disease .... " The '483 patent, 1: 17-20. Cacatian discloses that its
compounds have the same utility. See Cacatian 1-2.
Thus, in addition to the structural similarities between the compounds
disclosed in Cacatian and the compound of claim 1 of the '483 patent
(compare Cacatian 28 (compounds II and IV) to the '483 patent, 100:35--45
( structure of compound of claim 1) ), the compounds in Cacatian and the
compound of claim 1 of the '483 patent share the same utility. Accordingly,
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even acknowledging the structural differences between the compounds of
Cacatian and the compound of claim 1 of the '483 patent (see Appeal Br. 8-
9; Reply Br. 3--4), given those compounds' structural similarities and shared
utility, Appellants do not persuade us that the Examiner erred in relying on
the teachings in Cacatian when determining which organic acids would be
suitable for forming the pharmaceutical salt of the parent compound recited
in claim 1 of the '483 patent.
That Cacatian did not exemplify a camsylate compound, and that
camsylate was in a list of about 79 other useful pharmaceutically acceptable
salts, does not persuade us that a skilled artisan would have failed to
recognize from Cacatian that camsylate would be a useful pharmaceutically
acceptable salt form of the parent compound of claim 1 of the '483 patent.
See In re Mills, 470 F.2d 649,651 (CCPA 1972) ("All the disclosures in a
reference must be evaluated, including nonpreferred embodiments, and a
reference is not limited to the disclosure of specific working examples.")
(citations omitted)); Merck & Co. v. Biocraft Labs., Inc., 874 F.2d 804, 807
(Fed. Cir. 1989) (species claim held obvious where it recited one of 1200
possible combinations of embodiments disclosed by reference and where
reference suggested no preference for claimed embodiment).
Appellants also do not persuade us that our reviewing court has
recognized that selection of a pharmaceutically acceptable salt for a
therapeutic compound, as a general rule, is so unpredictable that choosing a
particular salt is unobvious. See Appeal Br. 8-10. As the Federal Circuit
explained in the factually similar Pfizer case:
[A] rule of law equating unpredictability to patentability,
applied in this case, would mean that any new salt - including
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those specifically listed in the [ drug compound-describing]
patent itself - would be separately patentable, simply because
the formation and properties of each salt must be verified
through testing. This cannot be the proper standard since the
expectation of success need only be reasonable, not absolute.
Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1364 (Fed. Cir. 2007).
In Pfizer the Federal Circuit directly addressed the obviousness of
choosing a pharmaceutically acceptable salt from among FDA approved
salts, and in doing so evaluated the teachings in Berge cited by Appellants.
See id. at 1362---63. Appellants do not persuade us, therefore, that the court's
later affirmance without comment of Valeant Int 'l (Barbados) SRL v.
Watson Pharms., Inc., No. 10-20526-CIV 2001 WL 6792653 (S.D.Fla.
Nov. 8, 2011), ajf'd sub nom. Valeant Int'! Bermuda v. Actavis, Inc., 534 F.
App'x. 999 (Fed. Cir. 2013), informs or controls the present fact situation
such that we may ignore Pfizer, particularly given the different evidence,
heightened burden of proof, and presumption of validity present in Valeant
as compared to this appeal.
We acknowledge, but are not persuaded by, Appellants' assertion that
in Sanofi-Synthelabo v. Apotex, Inc., 550 F.3d 1075, 1087 (Fed. Cir. 2008),
the Federal Circuit held, as a general rule, that "obviousness cannot be based
on the availability of after-the-fact testing." Appeal Br. 10. As noted above,
contrary to Appellants' characterization of Sanofi, the court in Pfizer
expressly held that verification of a salt's suitability through testing was not
a barrier to a conclusion of obviousness. See Pfizer, 480 F.3d at 1364.
Shire LLC v. Amneal Pharmaceuticals, LLC, 802 F.3d 1301 (Fed. Cir.
2015), involved the same elevated burden of proof and presumption of
validity in Valeant and Sanofi, which are not present in this appeal. See id.
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at 1306. Unlike the present situation and the situation in Pfizer, moreover,
Shire did not resolve the question of obviousness based on the selection of a
particular FDA-approved pharmaceutical salt. Rather, Shire based its
conclusion of non-obviousness on the prior art's failure to teach or suggest
preparing the salt's parent compound. See id. at 1308 (finding "no genuine
issue of material fact that [ the cited prior art reference] does not render
obvious the mesylate salts of LDX [(L-lysine-d-amphetamine), the claimed
parent compound]" because the reference "broadly teaches combining
amphetamine [the parent compound's precursor compound] with many
amino acids, protected and unprotected, and in different stereochemistries,
but provides no direction as to which of many possible choices is likely to be
successful ... Defendants can only come to LDX by 're-trac[ing] the path of
the inventor with hindsight"') (internal quotations omitted). Appellants
therefore do not persuade us that Shire informs or controls the present fact
situation.
We acknowledge the evidence advanced by Appellants to support the
proposition that the camsylate salt was one of the less commonly used FDA-
approved salts in the prior art. See Appeal Br. 10-11 (citing Berge ("[A]s of
1974 only 0.25% of all the FDA-approved commercially marketed salts
were camsylate salts."); also citing Bighley10 ("A more recent publication
similarly has indicated that as of 1993, only 0.59% of all the anionic
pharmaceutical salts in use were camsylate salts.")).
lO LYLE D. BIGHLEY ET AL., ENCYCLOPEDIA OF PHARMACEUTICAL
TECHNOLOGY, 453-99 (Vol. 13, James Swarbrick & James C. Boylan eds.,
1996) (App'x C).
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We acknowledge also Appellants' citation of the Makary 11 reference
and Handbook of Pharmaceutical Salts 12 as evidence that the camsylate salt
was known to possess certain properties making it one of the lesser desirable
pharmaceutical salts. See Appeal Br. 11. We first note that the Makary
reference (published 2014) does not appear to be prior art to the appealed
claims (earliest priority date in 2012), and Appellants point to nothing in the
reference suggesting that the cited portion reflected prior art knowledge in
relation to Appellants' claims. Nor do Appellants point to any specific
mention of the camsylate salt in the Makary reference.
Moreover, that the camsylate salt might be less preferred does not
negate the fact that both Berge and Bighley demonstrate that the camsylate
salt was known in the art to be one of a limited number of FDA-approved
salts useful for combination with pharmaceutically active compounds. See
In re Fulton, 391 F.3d 1195, 1200 (Fed. Cir. 2004) ("[O]ur case law does not
require that a particular combination must be the preferred, or the most
desirable, combination described in the prior art in order to provide
motivation for the current invention."); see also Pfizer, 480 F.3d at 1363
("That benzene sulphonate [the salt at issue] was only used in creating
0.25% of FDA-approved drugs is not highly probative, much less
dispositive. Indeed, beyond hydrochloride, which was used in
11 Patrick Makary, Principles of salt formation, 2 U.K. J. PHARM. BIOSCI. 1-
4 (2014) (App'x D).
12 HANDBOOK OF PHARMACEUTICAL SALTS[;] PROPERTIES, SELECTION, AND
USE 336 (P. Heinrich Stahl & Camille G. Wermuth eds., 2nd ed. 2011)
(App'x E).
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approximately 43% of approved drugs, almost all other salts could be
characterized as rarely used.") ( citing Berge; internal quotations omitted).
We acknowledge, but are unpersuaded by, Appellants' contention that
"a skilled artisan, even with the compound recited in claim 1 of the '483
patent in hand, would have had no reasonable expectation that any salt form
of this particular compound would be a therapeutically effective drug
candidate, let alone the presently claimed camsylate salt." Appeal Br. 12
( citing Patel 13).
It might be true, as Appellants contend, that skilled artisans knew that
different salts of the same pharmaceutical compound could potentially have
different bioavailabilities. See Patel 285-86. That fact, however, falls far
short of demonstrating that, given the evidence of record, a skilled artisan
lacked a reasonable expectation that a camsylate salt would be a useful
pharmaceutically acceptable salt of the parent compound recited in claim 1
of the '483 patent.
As noted above, in Pfizer our reviewing court squarely rejected a
standard of absolute predictability in relation to the choice of a known FDA-
approved salt for a known therapeutic compound. See Pfizer, 480 F.3d at
1364. In the present case, it might be true that it was not predictable with
absolute certainty that the camsylate salt would be a useful pharmaceutical
salt of the parent compound recited in claim 1 of the '483 patent.
As discussed above, however, the camsylate salt was among a limited
number of FDA-approved salts known to be useful with compounds having
13 Aateka Patel et al., Pharmaceutical salts: a formulation trick or a clinical
conundrum?, 16 BRITISH J. CARDIOL. 281-286 (2009) (App'x F).
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a similar structure and common utility with the '483 patent's claimed
compound. See Cacatian 28, 54--55; see also Berge 2 (listing all FDA-
approved salts including camsylate ); Bighley 454--56 (listing all salts
clinically evaluated in humans or commercially marketed through 1993
including camsylate ).
And, contrary to Appellants' contention that skilled artisans lacked a
reasonable expectation of successful salt formation, a number of the
references cited by Appellants show that skilled artisans routinely
determined which of the limited number of FDA-approved salts were useful
with a particular parent compound of interest, despite recognizing a degree
of unpredictability in the process. See Bighley 453 (Salt formation is
frequently performed on weak acidic or basic drugs because it is a relatively
simple chemical manipulation which may alter the physicochemical,
formulation, biopharmaceurical, and therapeutic properties of a drug without
modifying the basic chemical structure.") ( emphasis added); Patel 281 ("Salt
selection is now a common standard operation performed with small
ionisable molecules during drug development, and in many cases the drug
salts display preferential properties as compared with the parent molecule.")
( emphasis added); Remenar 14 990 (Salt selection is a strategy that is
commonly employed to improve properties of pharmaceutical compounds ..
. . Due to its central placement in chemical development and pharmaceutical
research, salt selection is becoming increasingly automated .... ").
14 Julius F. Remenar et al., Salt Selection and Simultaneous Polymorphism
Assessment via High-Throughput Crystallization: The Case of Sertraline, 7
0RG. PROC. RES. & DEVEL. 990-96 (2003).
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In sum, for the reasons discussed, Appellants do not persuade us that
the preponderance of the evidence fails to support the Examiner's
conclusion that the camsylate salt compound recited in Appellants' claim 1
would have been obvious to a skilled artisan in view of claim 1 of the '483
patent and Cacatian. We, therefore, affirm the Examiner's rejection of
Appellants' claim 1 for obviousness-type double patenting over claim 1 of
the '483 patent and Cacatian.
Analysis-Claims 2, 3, and 14
In traversing the Examiner's rejection of claims 2, 3, and 14 over
claim 1 of the '483 patent, Cacatian, Berge, and Fournet, Appellants do not
argue any claims separately. See Appeal Br. 13-17. We select claim 14 as
representative of the rejected claims. See 37 C.F.R. § 4I.37(c)(l)(iv).
Having carefully considered all of the arguments and evidence
advanced by Appellants and the Examiner, we find that the preponderance
of the evidence supports the Examiner's conclusion that the crystalline salt
compound recited in Appellants' claim 14 would have been obvious in view
of claim 1 of the '483 patent, Cacatian, Berge, and F oumet.
Appellants' claim 14 recites a camsylate salt of the same parent
compound recited in Appellants' claim 1, discussed above, and additionally
requires the salt to be in crystalline form. Appeal Br. 28. As discussed
above, we agree with the Examiner that the camsylate salt of the claimed
parent compound would have been obvious in view of claim 1 of the '483
patent and Cacatian.
As to the crystalline form recited in Appellants' claim 14, as the
Examiner pointed out, Berge discloses that a primary objective when
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preparing salts of therapeutic compounds is the formation of an easily
crystallized salt form. See Berge 1. As the Examiner also pointed out,
moreover, Fournet discloses that crystalline salts of therapeutic compounds
are advantageous in that they facilitate the implementation of the therapeutic
compound into pharmaceutical compositions. See Fournet, abstract. We
therefore discern no error in the Examiner's finding that a skilled artisan,
motivated to prepare a camsylate salt of the parent compound recited in
claim 1 of the '483 patent, also had good reason for, and a reasonable
expectation of success in, preparing a crystalline camsylate salt of the parent
compound recited in claim 1 of the '483 patent.
We acknowledge that the parent compounds in Fournet have different
structures than the compound of claim 1 of the '483 patent. See F oumet
,r 12. We are not persuaded, however, that a skilled artisan would have
understood Foumet's teachings regarding the advantageousness of
crystalline salt forms in relation to pharmaceutical formulation processes
(see id. at abstract, also id. ,r 10) to be applicable only to the particular
compounds described in the reference. Rather, Foumet's objective was to
prepare crystalline salt forms of its parent compounds which would in tum
render those compounds more amenable to formulation into pharmaceutical
compositions using known processes. See id.
Indeed, rather than undercutting the Examiner's position, the Remenar
reference cited by Appellants supports the Examiner's finding that skilled
artisans were aware of the advantages of preparing crystalline salt forms of
therapeutic compounds, and that, because of those advantages, such artisans
routinely engaged in the preparation of crystalline salt forms of therapeutic
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compounds of interest. See Remenar 990 ("Salt selection is a strategy that is
commonly employed to improve properties of pharmaceutical compounds.
Crystalline salts can confer useful attributes such as improved aqueous
solubility, chemical stability, and high bioavailability relative to those of the
free base or acid of the active compound.").
We acknowledge, similar to the discussion above, that it might not
have been absolutely predictable to make a specific polymorph of a
particular crystalline salt for every conceivable therapeutic compound of
interest, see Appeal Br. 15-16; claim 14, however, is directed simply to a
crystalline camsylate salt. Appellants do not provide sufficient evidence to
establish that once the camsylate salt form was made it would be
unpredictable that the salt would be crystalline. Rather, Appellants' cited
evidence is directed to the inherently unpredictable nature of polymorphism
of a crystalline salt (including whether such any polymorphs would be
stable). Moreover, regarding the crystalline camsylate salt, as discussed
above, obviousness does not require absolute predictability. See Pfizer, 480
F.3d at 1364. Because the record as a whole supports a finding that skilled
artisans routinely engaged in the preparation of crystalline salt forms of
therapeutic compounds of interest to obtain advantages with respect to
compounds' pharmaceutical properties, Appellants do not persuade us that a
skilled lacked a reasonable expectation of success in preparing the
crystalline camsylate salt form of the parent compound recited in claim 1 of
the '483 patent.
Accordingly, for the reasons discussed, Appellants do not persuade us
that preponderant evidence fails to support the Examiner's conclusion of
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obviousness as to Appellants' claim 14. We, therefore, affirm the
Examiner's obviousness-type double patenting rejection of Appellants'
claim 14 over claim 1 of the '483 patent, Cacatian, Berge, and F oumet.
Because they were not argued separately, claims 2 and 3 fall with claim 14.
See 37 C.F.R. § 4I.37(c)(l)(iv).
DOUBLE PATENTING-THE '911 PATENT
The Examiner's Prima Facie Case
In rejecting Appellants' claim 1 over claims 1 and 9 of the '911 patent
and Cacatian, the Examiner cited claims 1 and 9 of the '911 patent as
reciting pharmaceutically acceptable salts "of the racemic claimed
compound." Ans. 5. The Examiner noted that the specification of the '911
patent included non-toxic salts formed from organic acids among
pharmaceutically acceptable salts. Id. at 5---6.
The Examiner conceded that claims 1 and 9 of the '911 patent differed
from Appellants' claim 1 in that the claims of the '911 patent did not
"specifically teach the camsylate salt or the specific diastereomer" of
Appellants' claim 1. Id. at 6. The Examiner again cited Cacatian as
evidence that camsylate was known in the art to form pharmaceutically
acceptable salts with therapeutic compounds, and that it therefore would
have been obvious to form the camsylate salt of the parent compound recited
in claims 1 and 9 of the '911 patent, and thereby produce the camsylate salt
recited in Appellants' claim 1. See id. at 6-7.
As to the specific diastereomer of the parent compound recited in
Appellants' claim 1, the Examiner found that the specification of the '911
patent "teaches that the compounds may exist in particular geometric or
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stereoisomeric forms ( see column 12, lines 31-59)." Ans. 7. The Examiner
further found that
Id.
the fundamentals of optical activity and stereoisomerism are
well known to persons having ordinary skill in the art and a
person having ordinary skill in the art would have known how
to resolve the racemic mixture and would have been motivated
to do so with the reasonable expectation of achieving
ena[ n ]tiomers having substantially different pharmacological
activity.
In rejecting Appellants' claim 14 over claims 1 and 9 of the '911
patent, Cacatian, Berge, and F oumet, the Examiner reasoned that a skilled
artisan "would find it obvious and motivated to make the crystalline
camsylate salt of the claimed [parent] compound because '911 teach[es]
pharmaceutical acceptable salts of the claimed compounds, in which
camsylate is a known pharmaceutical salt as taught by Cacatian et al." Id. at
8.
The Examiner reasoned that the crystalline form of the camsylate salt
recited in Appellants' claim 14 would have been obvious in view of Berge's
teachings regarding the selection criteria for salt selection, which include
ease of crystallization. See id. at 7 (noting that "FDA-Approved
commercially marketed salts include camsylate, for example ( see table 1 [ of
Berge])"). The Examiner also noted that the "crystalline form of the salt of a
compound can help facilitate [its] implementation in the manufacture of
pharmaceutical compositions and be used to obtain the X-ray diffraction
profile as demonstrated by Fournet et al." Ans. 8.
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Analysis
In traversing the Examiner's rejections of Appellants' claims 1 and 14
over claims 1 and 9 of the '911 patent, Appellants contend that the same
arguments, addressed above in relation to claim 1 of the '483 patent, are
applicable. See Appeal Br. 17-18. For the reasons set forth above in
relation to the '483 patent, we do not find these arguments persuasive.
Appellants also note, as did the Examiner, that claims 1 and 9 of the
'911 patent do not recite the specific diastereomeric form of the parent
compound recited in Appellants' rejected claims 1 and 14. See id. Other
than pointing out this difference, however, Appellants do not explain why
the Examiner erred in determining that the specific form of the parent
compound recited in Appellants' claims 1 and 14 would have been obvious
in view of claims 1 and 9 of the '911 patent. As the Supreme Court has
explained, "the mere existence of differences between the prior art and an
invention does not establish the invention's nonobviousness." Dann v.
Johnston, 425 U.S. 219,230 (1976).
Appellants, moreover, do not dispute, assert error in, or provide
evidence controverting, the Examiner's express finding that the
fundamentals of optical activity and stereoisomerism were well known to
skilled artisans, and that a skilled artisan therefore would have known how,
and would have been motivated to, resolve the racemic mixture recited in the
claims of the '911 patent to arrive at the parent compound recited in
Appellants' claims 1 and 14. We are not persuaded, therefore, that
Appellants have shown error in the Examiner's determination that the
camsylate salt of Appellants' claim 1, and the crystalline camsylate salt
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recited in claim 14, would have been obvious in view of the compounds
recited in claims 1 and 9 of the '911 patent, when combined with the other
cited references as advanced by the Examiner. Accordingly, we affirm the
Examiner's rejection of Appellants' claim 1 over claims 1 and 9 of the '911
patent and Cacatian, and also affirm the Examiner's rejection of Appellants'
claim 14 over claims 1 and 9 of the '911 patent, Cacatian, Berge, and
Fournet.
DOUBLE PATENTING-THE '183 PATENT
The Examiner's Prima Facie Case
In rejecting Appellants' claim 1 over claims 1-13 of the '183 patent
and Cacatian, the Examiner cited claims 1-13 of the '183 patent as reciting
"a genus of compounds that encompass the claimed pharmaceutical salt of
the claimed compound." Ans. 8. The Examiner noted that the specification
of the '183 patent included non-toxic salts formed from organic acids among
pharmaceutically acceptable salts. Id at 9.
The Examiner conceded that claims 1-13 of the '183 patent differed
from Appellants' claim 1 in that the claims of the ' 183 patent did not "teach
the specific compound [ of Appellants' claim 1] and the camsylate salt or the
specific diastereomer." of Appellants' claim 1. Id.
The Examiner cited Cacatian as evidence that it would have been
obvious to form the camsylate salt of the parent compound recited in the
claims of the '183 patent, and reasoned that a skilled artisan aware of the
fundamentals of optical activity and stereoisomerism would have considered
it obvious to resolve the isomers of the compounds recited in the '183 to
produce the isomer recited in Appellants' claim 1. See Ans. 9-10.
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As to the structural differences between the parent compound recited
in Appellants' claim 1 and the compounds recited in the claims of the '183
patent, the Examiner asserted that "[i]t is well established that the
substitution of methyl for hydrogen on a known compound is not a
patentable modification absent unexpected or nonobvious results." Id. at 10.
In rejecting Appellants' claim 14 over claims 1-13 of the '183 patent,
Cacatian, Berge, and F oumet, the Examiner advanced a rationale similar to
that applied to claim 1, and applied Berge and Fournet as evidence that a
crystalline camsylate salt form would have been obvious. Id. at 10-12.
Analysis
We will reverse the rejections of Appellants' claims 1 and 14 based on
the claims of the '183 patent. As Appellants point out, claim 1 of the '183
patent requires the substituent at the R10 position to be halogen or methyl.
See the '183 patent 39:4.
In contrast, the parent compound recited in Appellants' claims 1 and
14 has no substituent at the corresponding position, meaning only a
hydrogen atom is present at that location. See Appeal Br. 25, 28.
Our reviewing court has advised that, although obviousness of a
claimed chemical compound may be based on structural similarity to another
compound, "it remains necessary to identify some reason that would have
led a chemist to modify [the] known compound in a particular manner to
establish prima facie obviousness of a new claimed compound." Takeda
Chem. Indus., Ltd. v. Alphapharm Pty., Ltd., 492 F.3d 1350, 1357 (Fed. Cir.
2007) ( emphasis added). In other words, establishing that a chemical
compound would have been obvious requires "a showing that the prior art
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would have suggested making the specific molecular modifications
necessary to achieve the claimed invention." Id. at 1356 (emphasis added;
internal quotations omitted).
In the present case, the Examiner has not identified any evidence in
the present record that would have suggested modifying the halogen or
methyl group present at the R10 position of the compounds recited in the
claims of the '183 patent, to arrive at the hydrogen atom present at the
corresponding position of the parent compound recited in Appellants' claims
1 and 14. Nor has the Examiner otherwise identified any reason why a
skilled artisan would have modified the compounds recited in the '183
patent to arrive at the compound of Appellants' claims 1 and 14.
Rather, as noted above, the Examiner states only that "[i]t is well
established that the substitution of methyl for hydrogen on a known
compound is not a patentable modification absent unexpected or nonobvious
results[,]" and cites a number of decisions by our reviewing court's
predecessor, and this Board's predecessor, in support of that proposition.
Ans. 10.
As our reviewing court has explained, however, "section 103 requires
a fact-intensive comparison of the claimed process with the prior art rather
than the mechanical application of one or another per se rule." In re Ochiai,
71 F.3d 1565, 1571 (Fed. Cir. 1995); see also id. at 1572 ("[R]eliance on per
se rules of obviousness is legally incorrect and must cease.").
Thus, it might be true that the courts or this Board previously have
held a similar chemical substitution to be obvious in relation to compounds
different than those at issue here. Those holdings, however, are no substitute
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for actual evidence or sound scientific reasoning that explain why a skilled
artisan would have made the specific modification of the particular
compounds involved here, the compounds of the claims of the '183 patent,
required to arrive at the compounds recited in Appellants' claims 1 and 14.
Accordingly, for the reasons discussed, we reverse the Examiner's
rejections of claims 1 and 14 over the claims of the '183 patent, as combined
with the other cited references.
DOUBLE PATENTING-THE '129 PATENT
The Examiner's Prima Facie Case
In rejecting Appellants' claim 1 over claims 1-16 of the '129 patent
and Cacatian, the Examiner cited the claims of the' 129 patent as reciting the
use of the parent compound recited in Appellants' claim 1, as well as
pharmaceutical salts thereof, in methods of treating disorders such as
Down's syndrome and dementia associated with Parkinson's. Ans. 12. The
Examiner noted that the specification of the' 129 patent included non-toxic
salts formed from organic acids among pharmaceutically acceptable salts. Id
at 12-13.
The Examiner conceded that claims 1-16 of the '129 patent differed
from Appellants' claim 1 in that the claims of the '129 patent did not
"specifically teach the camsylate salt" of the parent compound recited in
Appellants' claim 1. Id. at 13. The Examiner again cited Cacatian as
evidence that camsylate was known in the art to form pharmaceutically
acceptable salts with therapeutic compounds, and that it therefore would
have been obvious to form the camsylate salt of the parent compound recited
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in claims 1-16 of the '129 patent, and thereby produce the camsylate salt
recited in Appellants' claim 1. See Ans. 13.
In rejecting Appellants' claim 14 over claims 1-16 of the '129 patent,
Cacatian, Berge, and F oumet, the Examiner reasoned that a skilled artisan
"would find it obvious and motivated to make the crystalline camsylate salt
of the claimed [parent] compound because '129 teach[ es] pharmaceutical
acceptable salts of the claimed compounds, in which camsylate is a known
pharmaceutical salt as taught by Cacatian et al." Id. at 14.
The Examiner reasoned that the crystalline form of the camsylate salt
recited in Appellants' claim 14 would have been obvious in view of Berge's
teachings regarding the selection criteria for salt selection, which include
ease of crystallization. See id. (noting that "FDA-Approved commercially
marketed salts include camsylate, for example (see table 1 [ of Berge])").
The Examiner also noted that the "crystalline form of the salt of a compound
can help facilitate [its] implementation in the manufacture of pharmaceutical
compositions and be used to obtain the X-ray diffraction profile as
demonstrated by Fournet et al." Id. at 14--15.
Analysis
In traversing the Examiner's rejections of Appellants' claims 1 and 14
over claims 1-16 of the '129 patent, Appellants contend that the same
arguments, addressed above in relation to claim 1 of the '483 patent, are
applicable. See Appeal Br. 21-23.
For the reasons set forth above in relation to the '483 patent, we do
not find these arguments persuasive. Accordingly, we affirm the Examiner's
rejection of Appellants' claim 1 over claims 1-16 of the' 129 patent and
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Cacatian, and also affirm the Examiner's rejection of Appellants' claim 14
over claims 1-16 of the' 129 patent, Cacatian, Berge, and Fournet.
SUMMARY
For the reasons discussed, we affirm the Examiner's rejection of claim
1, on the ground of nonstatutory double patenting over claim 1 of the '483
patent and Cacatian.
For the reasons discussed, we affirm the Examiner's rejection of
claims 2, 3, and 14, on the ground of nonstatutory double patenting over
claim 1 of the '483 patent, Cacatian, Berge, and Fournet.
For the reasons discussed, we affirm the Examiner's rejection of claim
1, on the ground of nonstatutory double patenting over claims 1 and 9 of the
'911 patent and Cacatian.
For the reasons discussed, we affirm the Examiner's rejection of claim
14, on the ground of nonstatutory double patenting over claims 1 and 9 of
the '911 patent, Cacatian, Berge, and Fournet.
For the reasons discussed, we reverse the Examiner's rejection of
claim 1, on the ground of nonstatutory double patenting over claims 1-13 of
the ' 183 patent and Cacatian.
For the reasons discussed, we reverse the Examiner's rejection of
claim 14, on the ground of nonstatutory double patenting over claims 1 and
9 of the '183 patent, Cacatian, Berge, and Fournet (Ans. 10-12);
For the reasons discussed, we affirm the Examiner's rejection of claim
1, on the ground of nonstatutory double patenting over claims 1-16 of the
'129 patent and Cacatian.
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For the reasons discussed, we affirm the Examiner's rejection of claim
14, on the ground of nonstatutory double patenting over claims 1-16 of the
'129 patent, Cacatian, Berge, and Fournet.
TIME PERIOD
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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