Ex Parte Platscher et al

Patent Trial and Appeal Board

Nov 24, 2017

14118571 (P.T.A.B. Nov. 24, 2017)

United States Patent and Trademark Office
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
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
14/118,571 11/19/2013 Michael Wilhelm Platscher MERCK-4139 3378
23599 7590 11/28/2017
MILLEN, WHITE, ZELANO & BRANIGAN, P.C.
2200 CLARENDON BLVD.
SUITE 1400
ARLINGTON, VA 22201
EXAMINER
MURESAN, ANA Z
ART UNIT PAPER NUMBER
1671
NOTIFICATION DATE DELIVERY MODE
11/28/2017 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):
docketing@mwzb.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte MICHAEL WILHELM PLATSCHER and
ALFRED HEDINGER1
Appeal 2017-000331
Application 14/118,571
Technology Center 1600
Before JOHN G. NEW, TAWEN CHANG, and
TIMOTHY G. MAJORS, Administrative Patent Judges.
NEW, Administrative Patent Judge.
DECISION ON APPEAL
appellants state that the real party-in-interest is Merck Patent GmbH. App.
Br. 1.
Appeal 2017-000331
Application 14/118,571
SUMMARY
Appellants file this appeal under 35 U.S.C. § 134(a) from the
Examiner’s final rejection of claims 1—9 and 12—16.2 Specifically, claims 1—
6, 14, and 15 stand rejected as unpatentable under 35 U.S.C. § 102(b) as
being anticipated by Platscher et al. (US 8,853,283 B2, issued October 7,
2014 (“Platscher”))3 as evidenced by Feigner et al. (US 5,264,618, issued
November 23, 1993 (“Feigner”)), DeFerra et al. (WO 2005/049549 Al,
published June 2, 2005 (“DeFerra”)) and B. Rodriguez-Spong et al., General
principles of pharmaceutical solid polymorphism: a supramolecular
perspective, 56 Adv. DrugDeliv. Rev. 241—274 (2004) (“Rodriguez-
Spong”).
Claims 1—9 and 12—16 also stand rejected as unpatentable under 35
U.S.C. § 103(a) as being obvious over the combination of Platscher, Feigner,
DeFerra, and Rodriguez-Spong.
We have jurisdiction under 35 U.S.C. § 6(b).
We REVERSE.
NATURE OF THE CFAIMED INVENTION
Appellants’ invention is directed to crystal modifications of racemic
(2R,S)- and enantiomerically pure (2R)-resp, (2S)-DOTAP chloride, to
processes for the preparation thereof, and to the use thereof for the
preparation of pharmaceutical compositions. Spec., Abstract.
2 The Examiner’s rejection of claim 17 is withdrawn. Ans. 26.
3 The Platscher reference issued from an application that published as US
2008/0014254 Al, January 17, 2008 (the “’254 application”). Platscher is
also the co-inventor of the application presently on appeal. App. Br. 4, 5.
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Application 14/118,571
REPRESENTATIVE CLAIM
Claim 1 is representative of the claims on appeal and recites:
1. Crystalline (2R,S)-, (2S)- or (2R)-DOTAP chloride,
which crystalline (2R,S)-DOTAP chloride has one of the
following characteristics:
2 theta values comprising at least values of about 12.6,
about 19.5, about 20.2, about 21. 5 and about 25.2;
or
2 theta values comprising at least values of about 6.5,
about 12.6, about 13.4, about 19.5, about 20.2,
about 21.5, about 25.2 and about 29.8;
or
which crystalline (2S)-DOTAP chloride has one of the
following characteristics:
2 theta values comprising at least values of about 12.8,
about 19.5, about 19.8, about 20.2, and about 21.6;
or
2 theta values comprising at least values of about 6.5,
about 12.8, about 19.5, about 19.8, about 20.2,
about 20.7, about 21.6 and about 25.3;
or
which crystalline (2R)-DOTAP chloride has one of the
following characteristics:
2 theta values comprising at least values of about 12.8,
about 19.5, about 19.8, about 20.3, and about 21.6;
or
2 theta values comprising at least values of about 6.6,
about 12.8, about 19.5, about 19.8, about 20.3,
about 20.8, about 21.6 and about 25.3.
App. Br. 22.
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ISSUES AND ANALYSES
We decline to adopt the Examiner’s findings of fact and conclusions
that the appealed claims are anticipated and/or obvious over the cited prior
art. We address the arguments raised by Appellants below.
A. Rejection of claims 1—6, 14, and 15 under 35 U.S.C. $ 102(b)
Issue
Appellants argue the Examiner erred in finding that Platscher enables
one of ordinary skill in the art to make the particularly claimed crystalline
form of the compound. App. Br. 5.
Analysis
The application on appeal before us was filed by Appellants in
response to a prior rejection by the Office, during the prosecution of the
application that issued as Platscher, concluding that the Specification of the
Platscher application was not enabling, under 35 U.S.C. § 112, first
paragraph, for those claims in the application that were essentially the same
as the claims presently on appeal.4 App. Br. 5—6; see Platscher et al. (US
4 Canceled claim 2 of the ’254 application, by way of comparative example,
recites:
2. A crystalline form of (2R,S)—DOTAP chloride, which
exhibits a characteristic X-ray powder diffraction pattern for type
I:
with 2 theta values at 12.6, 19.5, 20.2, 21.5 and 25.2;
or
4
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Application 14/118,571
2008/0014254 Al, January 17, 2008) (the “’254 application” or “Platscher
application”) Final Act. 3—4, November 3, 2010. Appellants canceled those
claims of the Platscher application and subsequently filed this application to
add further descriptive matter to the Specification regarding the methods for
making the crystalline forms recited in the present claims. Id. at 6; see ’254
application, Non-Final Act. 3, March 29, 2011 (Rejection of claims 1—11,
27—29, 35, and 36 under 35 U.S.C. § 112, first paragraph withdrawn after
cancellation of the claims by Applicants). Specifically, Appellants contend
that their present application describes a process with very specific
conditions for crystallizing (2R,S)-, (2S)-, or (2R)-1 N,N,N-trimethyl-2,3-
bis[[ (9Z)-l-oxo-9-octadecenyl]oxy ]-l-propanaminium (“DOTAP”)
chloride. Id. (see Platscher col. 1,11. 9-10). Appellants argue that the
with 2 theta values at 16.5, 12.6, 13.4, 19.5, 20.2, 21.5,
25.2 and 29.8;
or
as shown in Fig. 1;
or
for type II:
with 2 theta values at 3.3, 4.9, 19.3, 20.0 and 23.5; or
with 2 theta values at 3.3,4.9,15.1,16.2,19.3, 20.0, 23.5
and 24.3; or
as shown in Fig. 2
or
for type III:
with 2 theta values at 2.8, 5.8, 20.0, 21.2 and 25.1; or
with 2 theta values at 2.8, 5.8. 12.9, 15.9, 20.0,21.2,25.1
and 29.4; or
as shown in Fig. 3.
’254 application, Amended Claims, August 30, 2010 at 1.
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current application discloses particular aprotic solvents selected from ether,
ketone or ester aprotic solvents and that the crystallizing takes place by slow
cooling at a rate of 0.001°C to 0.05°C per minute for 10 to 50 hours to a
temperature of -12°C or less. Id. (citing, e.g., claim 7).
The Examiner finds Platscher expressly teaches stable crystalline
(2R,S)-, (2S)-, and (2R)-DOTAP chloride compounds with similar x-ray
powder diffraction data, characterization data (e.g., stability, purity), and a
pharmaceutical composition thereof. Final Act. 2—3. The Examiner also
finds, based on the disclosures of Platscher, combined with teachings of
Feigner and DeFerra concerning synthesis of DOTAP chloride and
crystallization from aprotic solvent at lower temperature or crystallization of
amorphous DOTAP chloride from acetonitrile, and the high-throughput
methods of crystal growth taught by Rodriguez-Spong, that a person of
ordinary skill in the art would have been able to reproduce the results of
preparation of the claimed crystalline forms of enantiomerically pure
(2R,S)-, (2S)- and (2R)-DOTAP chloride compounds without undue
experimentation. Id. at 3.
Appellants argue that the evidence which supported the original
enablement rejection under 35U.S.C. § 112, first paragraph, during the
prosecution of the ’254 application, and the further evidence of record cited
by the Examiner, supports their contention that Platscher does not provide an
enabling disclosure to support the 35 U.S.C. §102 rejection. App. Br. 6.
Specifically, Appellants argue that Platscher discloses that the specific
crystalline forms of (2R,S)-DOTAP chloride or enantiomerically pure (2S)-
or (2R)-DOTAP chloride can be obtained by the recrystallization using a
large variety of aprotic solvents or aprotic solvent mixtures or aprotic/protic
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Application 14/118,571
solvent mixtures. Id. Appellants assert Feigner discloses the synthesis of
non-crystalline DOTAP chloride. Id. (citing Feigner Ex. 5). According to
Appellants, Feigner discloses that, after quatemizing of the pure compound,
the yellow wax product was crystallized from acetonitrile at a temperature of
-20°C, with additional purification of the crystals formed on a silica gel
column. Id. Appellants assert that the conditions described in Feigner
therefore fall within the general teachings of Platscher. Id. Furthermore,
Appellants argue, Feigner discloses that the cationic lipids (DOTAP
chloride) of the invention can be used in pharmaceutical formulations, and
that the effect of the cationic lipids in these formulations is to enhance the
potency and efficiency of the therapeutic agent by facilitating its
intracellular delivery. Id. (citing, e.g., Feigner col., 20 11. 28—30; 38-41).
Appellants next point to the Declaration of Dr. Marco S. Passafaro
(the “Passafaro Declaration”), in which Dr. Passafaro describes his attempt
to reproduce Example 5 of Feigner. App. Br. 7 (see Passafaro Decl. 1—2).
Appellants contend that, despite following all of steps of Feigner’s Example
5, Dr. Passafaro attests that he was unsuccessful in producing crystalline
DOTAP chloride by this method. Id. (see Passafaro Decl. 2—3).
Appellants argue that, during prosecution, the Examiner of the ’254
application found that the art of crystallization of DOTAP chloride was
unpredictable, based in part on the above finding that methods disclosed by
Feigner supra, which were described in the ’254 Specification, failed to
result in crystalline forms of DOTAP chloride. App. Br. 7. Appellants also
state that the Examiner of the ’254 application also found that a person of
ordinary skill in the art could not readily anticipate or predict which of the
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stated variety of aprotic solvents or aprotic solvent mixtures or aprotic/protic
solvent mixtures and conditions would produce the desired crystalline
DOTAP chloride, with the claimed X-ray powder diffraction pattern. Id. at
7-8.
Appellants argue that the Examiner of the ’254 application found that
the Specification provided no guidance for crystallization of DOTAP
chloride in a variety of aprotic solvents or aprotic solvent mixtures or
aprotic/protic solvent mixtures. App. Br. 8. Further, Appellants contend,
the Examiner found that the ’254 Specification did not provide any
disclosure as to which aprotic solvents or aprotic solvent mixtures or
aprotic/protic solvent mixtures produce crystalline DOTAP chloride with the
X-ray powder properties, i.e., 2 theta values, recited in the claims of the
(subsequently canceled) ’254 application, as well as in the instant claims.
Id. Appellants also assert that the Examiner of the ’254 application also
found that the Specification provided no examples of a method for making
crystalline (2RS)-, (2S)- or (2R)-DOTAP chloride, and ultimately concluded
that, considering the state of the art, the expert Declaration provided by the
’254 Applicants, the high unpredictability in the art and the lack of guidance
provided in the ’254 Specification, one of ordinary skill in the art would be
unable to practice the experiment without undue experimentation.5 Id. at 8.
Appellants also assert that the Specification of their application on
appeal provides enabling disclosures not present in Platscher. App. Br. 8.
5 Appellants point out that the surviving claims of the ’254 application (i.e.,
claims 1—3 of Platscher) are not directed to crystalline forms of DOTAP
chloride. App. Br. 8.
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Specifically, Appellants contend, their instant Specification explains and
demonstrates that a method more specified in its nature, i.e., with respect to
the solvents used and the rate of the cooling conducted for crystallization, is
necessary to prepare crystalline DOTAP chloride as recited in Appellants’
claims. Id. (citing, e.g., Spec. 9, 10, 11, 13). Appellants further point out
that the Examples provided in the Specification demonstrate that the use of
certain solvents and crystallizing at a particular cooling rate to a particular
temperature is necessary to produce the crystalline DOTAP chloride. Id. at
8—9 (citing Spec. 16—29).
Furthermore, Appellants argue, the Examiner has improperly shifted
the burden of proof upon Appellants by requiring Appellants to prove a
negative. App. Br. 9. Appellants point to the Examiner’s finding that:
“Appellants have not provided any evidence to show that a process for
making crystalline forms of DOTAP chloride was not known.” Id. (quoting
Non-Final Act. 7, March 19, 2015). Appellants assert that it is not clear how
Appellants could make such a showing other than that they have already
made, i.e., that none of the processes taught in the prior art result in the
crystalline forms of DOTAP chloride as claimed. Id. at 9—10.
Additionally, Appellants contend, and to add to their dilemma, the
Final Office action relies on Feigner to support enablement of the allegedly
anticipated claims, despite that the Examiner in the ’254 application relied
on this same reference to support lack of enablement of the same claims in
that application. App. Br 11. This, Appellants argue, despite the fact that
Platscher expressly discloses that it reproduced the Feigner method but that
it did not produce a crystalline product, the Examiner nevertheless now
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relies upon Feigner as evidence of enablement of synthesizing a crystalline
product. Id. (citing Platscher col. 3,11. 43—54).
With respect to the additional references cited by the Examiner in the
instant rejections, Appellants argue the disclosure of Platscher with respect
Feigner, and the Comparative Examples disclosed in Appellants’
Specification confirm that DeFerra’s disclosure that a “residue was
crystallized from acetonitrile at 20°C” is not reliable. App. Br. 12 (quoting
DeFerra 16). According to Appellants, DOTAP chloride is not soluble in
acetonitrile at this temperature, i.e., about room temperature, as disclosed by
Platscher. Id. Appellants argue that the description of the DeFerra method
regarding obtaining an oily substance and solidifying it is consistent with the
method described in Feigner, which Appellants have shown (and Platscher
discloses) does not provide a crystalline product. Id.
With respect to Rodriguez-Spong, Appellants argue the reference
provides no disclosure regarding obtaining crystals, particularly of DOTAP
chloride or, particularly, such crystals having the properties as recited in the
instant claims. App. Br. 13. Rather, Appellants contend, Rodriguez-Spong
discloses a very general statement regarding the potential for high
throughput crystallization methods. Id. (citing Rodriguez-Spong 264).
According to Appellants, Rodriguez-Spong suggests that such methods
allow testing of a large number of variables for providing different forms of
compounds, but discloses no connection between its disclosures and any
motivation for a person of ordinary skill in the art to look for a specific
crystalline form of DOTAP chloride. Id.
The Examiner responds that, because claims 1—6 and 14 are directed
to crystalline (2R,S), (2S)- and (2R)-DOTAP chloride compounds which are
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disclosed by the prior art, the method of producing said compounds is
irrelevant. Ans. 27.
The Examiner finds Platscher discloses anticipatory stable crystalline
(2R,S)-, (2S)- and (2R)-DOTAP chloride compounds with similar x-ray
powder diffraction data to the recited claims. Ans. 27. The Examiner finds
that the disclosed crystalline compounds were synthesized, purified, and
characterized more than one year prior to the filing date of Appellants’
instant application. Id. The Examiner points to Figure 1 of Platscher, which
the Examiner finds depicts x-ray spectra of a racemic DOTAP chloride,
which the Examiner finds matches the x-ray spectra of crystalline racemic
DOPTA chloride in Figure 1 of Appellants’ Specification. Id. The
Examiner finds the x-ray spectra of crystalline (2S)- or (2R)- DOTAP
chloride depicted in Figure 4 of Platscher matches the X-ray spectra of
enantiomerically pure crystalline DOTAP chloride depicted in Figures 2 and
3 of Appellants’ Specification. Id. Similarly, the Examiner finds Figure 6
of Platscher exhibits DSC spectra of racemic crystalline (2R,S)-DOTAP
chloride, enantiomeric crystalline (2R)- and (2S)-DOTAP chloride, which
demonstrates that crystalline compounds were made and enabled by
Platscher. Id. at 27—28.
Finally, the Examiner finds the ’254 application (which issued as
Platscher) discloses anticipatory crystalline (2R,S), (2S)- and (2R)-DOTAP
chloride compounds, wherein enantiomerically pure DOTAP chloride and
stable crystal modifications of racemic and enantiomerically pure DOTAP
chloride are reported and the X-ray characterization data of racemic DOTAP
chloride, and enantiomerically pure forms of DOTAP chloride (which is
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similar to the X-ray characterization data of instant compounds) are listed in
Table 2. Ans. 28 (also citing ’254 application || 33, 39-40).
We find Appellants’ arguments persuasive. A reference is
anticipatory under § 102(b) when it satisfies two particular requirements:
First, the reference must disclose each and every element of the
claimed invention, whether it does so explicitly or inherently. Eli
Lilly & Co. v. Zenith Goldline Pharms., Inc., 471 F.3d 1369,
1375 (Fed. Cir. 2006). While those elements must be “arranged
or combined in the same way as in the claim,” Net MoneyIN, Inc.
v. VeriSign, Inc., 545 F.3d 1359, 1370 (Fed. Cir. 2008), the
reference need not satisfy an ipsissimis verbis test, In re Bond,
910 F.2d 831, 832—33 (Fed. Cir. 1990). Second, the reference
must “enable one of ordinary skill in the art to make the invention
without undue experimentation.” Impax Labs., Inc. v. Aventis
Pharms. Inc., 545 F.3d 1312, 1314 (Fed. Cir. 2008).
In re Gleave, 560 F.3d 1331, 1334 (Fed. Cir. 2009). Neither Appellants nor
the Examiner dispute that Platscher discloses the claimed crystalline
DOTAP compounds. It is the second requirement that is at issue here.
Essentially, we are being asked to solve a virtual disagreement
between different Examiners, in successive prosecutions, as to whether
essentially identical claims to crystalline (2R)-, (2S)-, or (2R,S)- DOTAP
chloride are enabled by the Specification of the ’254 application. The
Examiner in the earlier prosecution concluded that they were not enabled,
and the Appellants canceled those claims and, subsequently, submitted
essentially the same claims in a new application with (they hoped) an
enabling Specification. The Examiner in the present appeal rejected the
claims as being anticipated by Platscher (which issued from the ’254
application). Appellants do not dispute that Platscher discloses each and
every element of the claimed invention, either explicitly or inherently.
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Consequently, we are faced with the question of whether the ’254
application/Platscher enables the claims in the present appeal.
Furthermore, we must consider the difference between the enablement
requirements of 35 U.S.C. § 112, first paragraph (the basis of the rejection in
the ’254 application), and those of 35 U.S.C. § 102(b) (the present rejection).
Our reviewing court, in summarizing the difference, has held that, unlike
rejections under the first paragraph of Section 112, a rejection under Section
102 need disclose no independent use or utility to anticipate a claim.
Gleave, 560 F.3d at 1335 (citing, e.g., Novo Nordisk Pharms., Inc. v. Bio—
Tech. Gen. Corp., 424 F.3d 1347, 1355 (Fed. Cir. 2005) (“The standard for
enablement of a prior art reference for purposes of anticipation under [§] 102
differs from the enablement standard under 35 U.S.C. § 112”); Rasmusson v.
SmithKline Beecham Corp., 413 F.3d 1318, 1326 (Fed. Cir. 2005) (“[A]
prior art reference need not demonstrate utility in order to serve as an
anticipating reference under [§] 102”); In re Hafner, 410 F.2d 1403, 1405
(1969) (“[Section] 112 provides that the specification must enable one
skilled in the art to ‘use’ the invention whereas § 102 makes no such
requirement as to an anticipatory disclosure”).
In the prosecution of the ’254 application, the Examiner rejected the
claims at issue under § 112, first paragraph, as “containing] subject matter
which was not described in the specification in such a way as to enable one
skilled in the art to which it pertains, or with which it is most nearly
connected, to make and/or use the invention. ’254 Appl. Final Act. 3—4,
November 3, 2010. Specifically, the Examiner concluded:
The art of recrystallization of DOTAP chloride is deemed
unpredictable, based upon the fact that the prior art of Feigner et
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al. used an aprotic solvent of acetonitrile for crystallization,
Applicant teaches that the aprotic solvent of acetonitrile is useful
in recrystallization; and Applicant’s Declaration discloses that
DOTAP chloride cannot be recrystallized from the aprotic
solvent acetonitrile. Because on the above facts it is clear that
one skilled in the art, at the time of Applicant’s claimed
invention, could not readily anticipate or predict which of the
stated variety of aprotic solvents or aprotic solvent mixtures or
aprotic/protic solvent mixtures would produce the desired
crystalline DOTAP chloride, with the claimed X-ray powder
diffraction pattern.
Id. at 8. It is therefore evident that the Examiner in the ’254 application
concluded that the claims are not enabled because the Specification failed to
provide sufficient guidance, in an unpredictable art, to direct a person of
ordinary skill to synthesize (i.e., to make) the crystalline DOTAP chloride
without undue experimentation. Therefore, under the Examiner’s analysis in
the ’254 application, the Specification would fail to enable the claims under
either a § 112, first paragraph, or a § 102 analysis, both of which require
enabling a person of ordinary skill in the art to be able to make the claimed
compound without undue experimentation. Gleave, 560 F.3d at 1335.
We next turn to whether Platscher anticipates the claims currently on
appeal and, specifically, whether it provides an enabling disclosure under
§ 102. Under the prior Examiner’s reasoning it does not, for it fails to
enable the skilled artisan to synthesize crystalline (2R)-, (2S)-, or (2R,S)-
DOTAP chloride without undue experimentation in an unpredictable art.
’254 Appl. Final Act. 8.
The Examiner in this appeal finds (and Appellants do not dispute) that
Platscher discloses the claimed compounds, as evidenced not least by the
identical x-ray spectra and DSC curves in both Platscher and Appellants’
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Specification. See Ans. 27—28. However, the Examiner does not adduce
any persuasive findings or evidence to indicate that Platscher would teach a
person of ordinary skill how to make the claimed compounds without undue
experimentation, nor does the Examiner provide any evidence that directly
contradicts the findings of the Examiner in the prior ’254 application.
Feigner, which is cited by the present Examiner as evidence of enablement,
was cited by the Examiner in the prosecution of the ’254 application as
providing evidence of lack of enablement. ’254 Appl. Final Act. 8. Feigner
is also cited in both Platscher and in the ’254 application:
Feigner et al., U.S. Pat. No. 5,264,618, carry out the methylation
of the corresponding dimethylamino compound directly to
DOTAP chloride by means of methyl chloride. They apparently
obtain a yellow wax by crystallisation from acetonitrile at -20°
C. However, DOTAP chloride is virtually insoluble in
acetonitrile at room temperature. Attempts to reproduce this so-
called crystallisation gave only amorphous material through
solidification of the oily substance obtained from hot solution on
cooling. The fact that this is not a crystallization is also evident
from the fact that the authors apparently do not achieve a
purification effect and have to purify the substance by
chromatography.
Platscher col. 3,11. 43—54 (emphasis added); see also ’254 application 130.
Although prior art patents and publications are generally presumed enabling,
based on the unique facts and the evidentiary record here, we agree with the
prior Examiner and Appellants that this teaching of Platscher is not an
enabling disclosure of the synthesis of crystalline DOTAP chloride as
required by the claims.
DeFerra, also relied upon as evidence of enablement by the Examiner,
recites:
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50 g of crude DOTAP-OTs (obtained in Example 4 - titre
66%, 39.6 mmol) was dissolved in 150 ml of methanol; this
solution was loaded into a chromatography column packed with
230 ml of strong basic IRA 404 ion-exchange resin, chloride
form (produced by Rohm & Haas), previously washed with 1.2
1 of distilled water and placed in a methanol environment (1.2
1). The methanolic solution containing the DOTAP-OTs was
then eluted by gravity with a flow of 2.5 m./minute, a dead
volume of about 50 ml being discarded. Finally, the elution of
the product with methanol was completed, and a single fraction
of about 600 ml was collected. This solution was concentrated in
a Rotavapor apparatus to a volume of 100 ml and then 100 ml of
acetonitrile was added to this solution and brought to an oily
residue (44.0 g) in the Rotavapor apparatus. This residue was
crystallized from acetonitrile at 20°C. 20.7 g (29.7 mmol) of
DOTAP-Cl, yield 75% was obtained after drying overnight
under high vacuum at ambient T.
DeFerra 16 (emphasis added). Appellants contend this teaching is not
reliable because the method taught by DeFerra is consistent with the method
taught by Feigner, the Passafaro Declaration, and the comparative examples
of Appellants’ Specification, which demonstrate that DOTAP is not soluble
in acetonitrile at 20°C and does not produce a crystalline product. See App.
Br. 12. Appellants argue that DeFerra does not prove that the obtained
product is crystalline, suggesting that: “It is not uncommon in the art for
such unproven assumptions to be made about solid products being
crystalline.” Ans. 27—28. We find that, given the potentially contradictory
results between DeFerra, on the one hand, and Feigner, the Passafaro
Declaration, and Appellants’ Specification, on the other, we agree with the
prior Examiner’s finding that the art, at least with respect to the methods
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described in these references, is unpredictable and could not have been
achieved by a person of ordinary skill without undue experimentation.
Finally, we find that Rodriguez-Spong is silent with respect to the
synthesis of crystalline DOTAP chloride and does not otherwise enable the
synthesis of the claimed compounds.
We therefore agree with the prior Examiner in the prosecution of the
’254 application that Platscher, as evidenced by Feigner, DeFerra, and
Rodriguez-Spong does not enable Appellants’ claims. We therefore reverse
the Examiner’s rejection of claims 1, 3, 5—6, and 14—15. Appellants argue
claims 2 and 4 separately, incorporating their arguments and providing
additional arguments for each claim, respectively. However, because, as we
have explained, we are persuaded by Appellants’ arguments related supra,
we need not reach Appellants’ additional arguments and we reverse the
rejection of claims 2 and 4 on that ground.
B. Rejection of claims 1—9 and 12—16 under 35 U.S.C. $ 103(a)
Appellants repeat their arguments supra with respect to the failure of
the cited references to provide an enabling disclosure, as well as providing
additional arguments. See App. Br. 16—20. “Under § 103, a reference need
not be enabled; it qualifies as prior art, for whatever is disclosed therein.”
Amgen, Inc. v. Hoechst Marion Roussel, Inc., 314 F.3d 1313, 1357 (Fed. Cir.
2003); see also Symbol Techs. Inc. v. Opticon Inc., 935 F.2d 1569, 1578
(Fed. Cir. 1991) (“[A] non-enabling reference may qualify as prior art for
the purpose of determining obviousness under § 103.”). The question,
therefore, of whether Platscher is enabling of Appellants’ claims is not
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directly relevant to whether Platscher is prior art for purposes of obviousness
under 35 U.S.C. §103.
Nevertheless, and as we have explained supra, the Examiner adduces
no evidence or finding in the cited prior art references that teach or suggest a
means of synthesizing crystalline (2R)-, (2S)-, or (2R,S) DOTAP chloride.
In other words, although Platscher or the other references need not
themselves individually be enabling, one of the references must be. And we
have determined, supra, that none of them are on this key issue.
The Examiner relies upon essentially the same findings for supporting
the conclusion of obviousness as for the conclusion of anticipation. See
Ans. 29—24. The Examiner further points to paragraphs [0042]—[0054] of
the ’254 application, which teaches, inter alia, that:
The invention furthermore relates to a process for the
preparation of DOTAP chloride crystal modifications which is
characterised in that DOTAP chloride is crystallised from an
aprotic medium. The aprotic medium used for this purpose can
be aprotic solvents [including acetonitrile] or mixtures thereof.
The crystallisation of the DOTAP chloride modifications is
generally achieved specifically by slow cooling of the prepared
solution to temperatures below 30°C. The formation of the
crystals is carried out either spontaneously or by inoculation with
the corresponding DOTAP chloride crystal modification.
However, the prior Examiner, citing the contradictory disclosures of
Feigner and the examples of the ’254 application, determined that this
generic method was not enabling under 35 U.S.C. § 112, first paragraph, and
we can discern no teaching or suggestion in any of the references that is
otherwise enabling of the claims on appeal. Consequently, we disagree with
18
Appeal 2017-000331
Application 14/118,571
the Examiner that the combined cited prior art teaches an enabling method
of synthesizing the claimed compounds and we reverse the Examiner’s
rejection of the claims.
DECISION
The Examiner’s rejection of claims 1—6, 14, and 15 as unpatentable
under 35 U.S.C. § 102(b) is reversed.
The Examiner’s rejection of claims 1—9 and 12—16 as unpatentable
under 35 U.S.C. § 103(a) is reversed.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(1). See 37 C.F.R.
§ 1.136(a)(l)(iv).
REVERSED
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