Ex Parte Collin et al

Patent Trial and Appeal Board

Jun 15, 2016

11995476 (P.T.A.B. Jun. 15, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
111995,476 10/30/2008
23416 7590
POLSINELLI PC
(DE OFFICE)
1000 Louisiana Street
Fifty-Third Floor
HOUSTON, TX 77002
06/17/2016
FIRST NAMED INVENTOR
Andre' Collin
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.
34388-00001-US 8105
EXAMINER
NIEBAUER, RONALD T
ART UNIT PAPER NUMBER
1676
NOTIFICATION DATE DELIVERY MODE
06/17/2016 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):
dcdocketing@novakdruce.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte ANDRE COLLIN and THIERRY TAMBUYSER1
Appeal2013-008994
Application 11/995,476
Technology Center 1600
Before DONALD E. ADAMS, JEFFREY N. FREDMAN, and
DEVON ZASTROW NEWMAN, Administrative Patent Judges.
NEWMAN, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a process
for manufacturing the drug eptifibatide acetate. The Examiner finally
rejected the claims as obvious. We have jurisdiction under 35 U.S.C. § 6(b).
We affirm.
STATEMENT OF THE CASE
Background
Eptifibatide is a therapeutic drug used to inhibit platelet aggregation
by selectively blocking the platelet glycoprotein IIb/IIa receptor. (Spec. 1,
1 Appellants identify the Real Party in Interest as Solvay (Societe Anonyme)
("Solvay") of Brussels, Belgium. (App. Br. 1.)
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Application 11/995,476
ll:3-8). Eptifibatide is used to treat patients during coronary angioplasty,
myocardial infarction and angina, including as the active agent in the drug
Integrilinâ„¢. (Id., 3-12) Appellants claim a need for a process to
manufacture sufficient quantities of purified eptifibatide at an acceptable
cost. (Id., 11. 19-21 ).
The Claims
The claims at issue regard a method of manufacture of eptifibatide
acetate comprising subjecting a solution of eptifibatide acetate in a mixture
of water/solvent/acetic acid to an evaporation step, wherein the pH of the
solution prior to evaporation is less than or equal to 7. Claims 1-7, 9, 12,
15-18 and 21-23 are on appeal. 2 Independent claim 1 is representative and
reads as follows (formatting added):
1. A process for manufacturing eptifibatide acetate
comprising subjecting a solution of eptifibatide acetate in a
mixture of water/solvent/acetic acid to an evaporation step
comprising evaporating the solvent,
and further comprising adding water to the solution
during the evaporation step to reduce the solvent content of the
solution to less than or equal to 20 mg/kg,
wherein the evaporation step is carried out at a
temperature of 0°C to 40°C,
and wherein the pH of the solution prior to evaporation is
less than or equal to 7.
2 Claims 8, 10-11, 13, 14, 19, and 20 were cancelled. (Final Office Action,
2).
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Application 11/995,476
The Issue
The Examiner rejected claims 1-7, 9, 12, 15-18 and 21-23 under 35
U.S.C. § 103(a) as being unpatentable over Evans3, Integrilin product
information4, Felton5, and Vigneaud6. (Ans. 6).
The issue presented is: Does the evidence of record support the
Examiner's conclusion that Evans, the Integrilin product information,
Felton, and Vigneaud suggest the claimed method of manufacturing
eptifibatide acetate?
Findings of Fact
1. Evans teaches that eptifibatide is a compound with the known
therapeutic uses of treatment of patients with acute coronary syndrome and
those undergoing percutaneous coronary intervention. (Evans 1, 11:4--9).
2. Evans discloses that there is a need "for a process by which
peptide amides such as eptifibatide may be economically produced in high
purity on a large scale." (Evans, 2, 11:3--4).
3. The Integrelin Data Sheet teaches that the acetate salt of
eptifibatide ( eptifibatide acetate) may be therapeutically administered in
solution form. (Integrelin, 1-2).
3 WO 2003/093302 A2, published Nov. 13, 2003
4 "Integrilin Solution for Injection", Information for Health Professionals
Data Sheet, provided by Schering-Plough, dated Sept. 27, 2006
5 Felson, M., "Evaporators", Today's Chemist at Work, May 2004, pp. 47-50
6 Vigneaud et al., The sequence of amino acids in oxytocin, with a proposal
for the structure of oxytocin, 205 J. Biol. Chem. 949-957 (1953).
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Application 11/995,476
4. Evans discloses a method of manufacture of eptifibatide using
solid phase synthesis. (Evans, 10: 16-13:35).
5. Evans teaches a suspension of eptifibatide peptide amide in
acetonitrile and water, followed by method of purification of eptifibatide in
which "the cyclised peptide amide solution ... [is] acidified with 10% citric
acid in water . . . purified by preparative HPLC ... and further purified by
salt exchange, desalting, evaporation and lyophilisation to yield the pure
cyclic peptide amide." (Evans 13:13-14:14).
6. Felton teaches that evaporation is a chemical process for
removing solvents, and that rotary evaporators can use a vacuum to remove
a vaporized solvent. (Felton, 47--48).
7. Vigneaud teaches that for a solution of oxytocin dissolved in
equal volumes of concentrated HCl and glacial acetic acid, the acid may be
removed by evaporation under reduced pressure through repeated
evaporation with water at 37°C under an atmosphere of nitrogen for 6 days.
(Vigneaud, 949).
8. A BP technical brochure7 regarding acetic acid teaches that
acetic acid does not form azeotropes with water. (BP Brochure, 3).
Principles of Law
An invention is not patentable under 35 U.S.C. § 103 if it is obvious.
KSR Int'! Co. v. Teleflex Inc., 550 U.S. 398, 427 (2007). Under§ 103: the
scope and content of the prior art are to be determined; differences between
the prior art and the claims at issue are to be ascertained; and the level of
7 BP Technical Brochure, Acetic Acid 1--4 (2003).
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Application 11/995,476
ordinary skill in the pertinent art resolved. Against this background, the
obviousness or nonobviousness of the subject matter is determined.
Graham v. John Deere Co., 383 U.S. 1, 17 (1966).
A central question in analyzing obviousness is "whether the
improvement is more than the predictable use of prior art elements according
to their established functions." Id. ("[W]here the general conditions of a
claim are disclosed in the prior art, it is not inventive to discover the
optimum or workable ranges by routine experimentation." In re Aller, 220
F.2d 454, 456 (CCPA 1955).
"Under the proper legal standard, a reference will teach away when it
suggests that the developments flowing from its disclosures are unlikely to
produce the objective of the applicant's invention. A statement that a
particular combination is not a preferred embodiment does not teach away
absent clear discouragement of that combination." Syntex (U.S.A.) LLC v.
Apotex, Inc., 407 F.3d 1371, 1380 (Fed. Cir. 2005) (citations omitted).
Analysis
We adopt the Examiner's findings of fact and reasoning regarding the
scope and content of the prior art (Ans. 6-9, 14) and agree that the claims
are rendered obvious by the combination of Evans, Integrilin product
information, Felton, and Vigneaud. We address Appellants' arguments
below.
Appellants contend the references teach away from the claimed
invention and are therefore not combinable to establish a prima facie case of
obviousness. Specifically, Appellants claim "the prior art actively avoids
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Application 11/995,476
the use of acetic acid at a pH of less than or equal to 7, and teaches away
from the use of acetic acid for the purification of eptifibatide." (App. Br. 6).
Appellants argue four points in support of their proposition.
First, Appellants note that Evans discloses the use of acetic acid only
in the step (peptide amide cyclisation) that occurs prior to - but not in -
purification of eptifibatide, to adjust the pH value of the solution containing
the synthesized peptide amide. (App. Br. 6). Appellants contend it "would
be reasonable to infer from the teachings of Evans that acetic acid is, or
should be, specifically avoided in the purification step." (Id.).
Second, Appellants cite to Evans' disclosure that the peptide should
be precipitated with an inert solvent that will not affect its integrity. (App.
Br. 7, citing Evans 5, 11. 5-9). Appellants argue that their disclosed solution
of acetic acid, water and organic solvent (particularly acetonitrile) is not
inert and therefore is not contemplated, taught or suggested by Evans. (App.
Br. 7).
Third, Appellants note that Evans teaches cooling, pooling and further
purifying a peptide by salt exchange, desalting, evaporating and lyophilizing
peak fractions obtained from HPLC during the purification process. (App.
Br. 7, citing Evans 14). Appellants argue that the "desalting" step is used to
remove the salt-forming acid from the solution containing the synthesized
peptide amide prior to subjecting the solution to an evaporation step,
whereas the claimed invention uses the acetic acid to accomplish the
evaporation. (App. Br. 8). Hence, Appellants argue Evans teaches away
from subjecting a solution of eptifibatide containing acetic acid to an
evaporation step during the purification process. (Id.).
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Finally, Appellants argue that acetic acid is volatile and forms an
azeotrope with water, precluding removal of acetic acid alone through the
repeated vacuum evaporation with water disclosed by Vigneuad. (Id.).
Instead, water and acetic acid would be removed at an equal rate, which
would not accomplish the object of the invention. (Id.). Appellants argue
their claimed process achieves a "surprising" different result: subjecting a
solution of eptifibatide acetate in a mixture of water/solvent/acetic acid to an
evaporation step resulted in evaporation of the water and solvent
components only, leaving a concentrated solution of eptifibatide acetate.
(Id.).
We find each of Appellants' arguments unpersuasive because Evans
does not criticize, discredit or otherwise discourage the use of acetic acid,
such as an admonition that acetic acid should not be used at a pH of less than
or equal to 7, should not be used for purification of eptifibatide because it
forms an azeotrope with water, or that acetic acid should be avoided because
it would negatively affect the integrity of eptifibatide. Rather, Evans
discloses the use of acetic acid in steps prior to purification with no adverse
effect on the peptide. (Evans 13). Evans' disclosure of an alternative acid
for the purification step does not "teach away" without such express
discouragement: the "prior art's mere disclosure of more than one
alternative does not constitute a teaching away from ... alternatives because
such disclosure does not criticize, discredit, or otherwise discourage the
solution claimed." In re Fulton, 391 F.3d 1195, 1201 (Fed. Cir. 2004).
With regard to the disclosure in Vigneaud, we agree with the
Examiner that removal of acetic acid is separate and distinct from removal
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Application 11/995,476
of a peptide or a peptide bound to another molecule, as would be the case
with eptifibatide acetate. (Ans. 15). In addition, the Examiner's evidence
that acetic acid does not form an azeotrope with water (as Appellants claim)
is unrebutted. Finally, Appellants have failed to provide evidence of their
"surprising" results sufficient to overcome obviousness. "[W]hen
unexpected results are used as evidence of nonobviousness, the results must
be shown to be unexpected compared with the closest prior art." In re
Baxter Travenol Labs., 952 F.2d 388, 392 (Fed. Cir. 1991). Appellants'
arguments without more do not meet this requirement. See In re Geisler,
116 F.3d 1465, 1470 (Fed. Cir. 1997) ("[A]ttomey argument [is] not the
kind of factual evidence that is required to rebut a prima facie case of
obviousness").
Appellants next argue that the cited references do not provide
evidence that there would be a reasonable expectation of success for the
claimed invention. (App. Br. 5). Specifically, Appellants argue Evans
provides insufficient information to give a reasonable expectation of success
in the use of a water/solvent/acetic acid mixture and that Vigneaud and
Felton provide general disclosure only, with no specific application
sufficient to provide a reasonable expectation of success for the disclosed
techniques with the claimed invention. (Br. 10-12).
We find that the cited references provide a reasonable expectation of
success in making the claimed invention. Integrillin provides evidence that
the ordinary artisan would have had reason to synthesize purified
eptifibatide and eptifibatide acetate (FF 3). Acetic acid is a known source of
acetate in chemical processes. (Ans. 7). Evans expressly teaches use of
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acetic acid during the cyclisation step, demonstrating its compatibility with
eptifibatide. (Evans 13). Vigneaud discloses a process of evaporation of
glacial acetic acid with water that one of skill in the art would have
recognized as applicable to the process of Evans for synthesis of the
eptifibatide acetate form taught by Integrillin. (Vigneaud 949). The
Examiner has submitted evidence rebutting Appellants' argument regarding
formation of an azeotrope between acetic acid and water, and Appellant has
not overcome this evidence. (BP Brochure, 3). Hence, the factual record
supports the Examiner's rejection. "Obviousness does not require absolute
predictability of success .... For obviousness under§ 103, all that is
required is a reasonable expectation of success." In re 0 'Farrell, 853 F.2d
894, 903---04 (Fed. Cir. 1988).
Conclusion of Law
The evidence of record supports the Examiner's conclusion that
Evans, the Integrilin product information, Felton, and Vigneaud suggest the
claimed method of manufacturing eptifibatide acetate. Claims 2-7, 9, 12,
15-18 and 21-23 have not been argued separately and therefore fall with
claim 1. 37 C.F.R. § 41.37( c )(1 )(iv).
SUMMARY
We affirm the rejection of claims 1-7, 9, 12, 15-18 and 21-23 on the
basis of obviousness.
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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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