Ex Parte Dumas et al

Patent Trial and Appeal Board

Nov 23, 2016

11212109 (P.T.A.B. Nov. 23, 2016)

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.
11/212,109 08/26/2005 Jacques Dumas BAYER-0052 5925
23599 7590 11/28/2016
MILLEN, WHITE, ZELANO & BRANIGAN, P.C.
2200 CLARENDON BLVD.
SUITE 1400
ARLINGTON, VA 22201
EXAMINER
SZNAIDMAN, MARCOS L
ART UNIT PAPER NUMBER
1628
NOTIFICATION DATE DELIVERY MODE
11/28/2016 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):
docketing@mwzb.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte JACQUES DUMAS, PAUL EHRLICH, and
SUSANNE ZULEGER
Appeal 2014-008008
Application 11/212,109
Technology Center 1600
Before DONALD E. ADAMS, DEMETRA J. MILLS, and
JOHN E. SCHNEIDER, Administrative Patent Judges.
MILLS, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35U.S.C. § 134. The Examiner has rejected
the claims for obviousness-type double patenting. We have jurisdiction
under 35 U.S.C. § 6(b).
WE AFFIRM.
Appeal 2014-008008
Application 11/212,109
STATEMENT OF CASE
The following claim is representative.
1. A composition comprising:
a) 4{4-[3-(4-chloro-3-trifluoromethylphenyl)-ureido ]-3-
fluorophenoxy}-pyridine-2-carboxylic acid methyl amide of Formula I
and/or salts, hydrates., or solvates thereof, and b)
a pharmaceutically acceptable matrix agent in the form of a solid
dispersion, wherein the pharmaceutically acceptable matrix agent comprises
at least one polymer which is polyvinylpyrrolidone, copovidone,
vinylpyrrolidone/ vinylacetate copolymer, crospovidone, polyalkylene glycol,
including polyethylene glycol; polyethylenoxide, poloxamer, hydroxyalkyl
cellulose, including hydroxypropyl cellulose; hydroxyalkyl methyl cellulose,
including hydroxypropyl methyl cellulose; carboxymethyl cellulose, sodium
carboxymethyl cellulose, ethyl cellulose, cellulose succinates, cellulose
phthalates, polymethacrylates, polyhydroxyalkylacrylates,
polyhydroxyalkylmethacrylates, polyacrylates, polyvinyl alcohol, polyvinyl
acetate, vinyl alcohol/vinyl acetate copolymer, xanthan gum,
galactomannanes, carrageenan, chitosan, chitin, alginic acid, salts of algininc
acid, polylactides, dextrins, starch, starch derivatives, proteins or
polyethylene oxide.
App. Br. 14 (Claims Appendix).
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Application 11/212,109
Cited References
Riegelman et al.
Nakamichi et al.
Aoki
Appel
Juppo
Boyer et al.
Hirose et al.
Bateman et al.
US 4,151,273
US 5,456,923
US 2003/0099703 Al
US 2003/0224043 Al
US 2004/0067256 Al
US 8,637,553 B2
EP 1275386 Al
WO 03/043630 Al
Apr. 24, 1979
Oct. 10, 1995
May 29, 2003
Dec. 4, 2003
Apr. 8, 2004
Jan. 28, 2014
Jan. 15, 2003
May 30, 2003
Abu T. M. Serajuddim, Solid Dispersion of Poorly Water-Soluble Drugs:
Early Promises, Subsequent Problems, and Recent Breakthroughs, Vol. 88
No. 10 J. Pharmaceutical Sciences 1058-66 (1999).
Christian Leuner and Jennifer Dressman, Improving drug solubility for oral
delivery using solid dispersions, 50 European J. Pharmaceutics and
Biopharmaceutics 47-60 (2000).
Grounds of Rejection
Claims 1, 3—22 and 36-451 stand provisionally rejected on the ground
of nonstatutory obviousness-type double patenting as being unpatentable
over claims 1—6, 9-11 and 56—58 of copending Application No. 10/895,985
(now US 8,637,553 to Boyer et al. (hereinafter, Boyer)), in view of Leuner,
Serajuddim, Aoki, Juppo, Bateman, Appel, Hirose, Nakamichi and
Riegelman.
FINDINGS OF FACT
The Examiner’s findings of fact are set forth in the Answer at pages
3—9 and Final Act., pages 4-8.
1 Claims 25, 46 and 47 have been withdrawn from consideration by the
Examiner as directed to a non-elected invention. Ans. 3.
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PRINCIPLES OF LAW
In making our determination, we apply the preponderance of the
evidence standard. See, e.g., Ethicon, Inc. v. Quigg, 849 F.2d 1422, 1427
(Fed. Cir. 1988) (explaining the general evidentiary standard for proceedings
before the Office).
Obviousness-type double patenting entails a two-step analysis. First,
the allegedly conflicting claims are construed and, second, the difference(s)
between the claims are considered to determine whether the claims are
patentably distinct. See, Eli Lilly & Co. v. Barr Labs., Inc., 251 F.3d 955,
968, (Fed. Cir. 2001). “A later patent claim is not patentably distinct from
an earlier patent claim if the later claim is obvious over, or anticipated by,
the earlier claim.” Id.
All proper double patenting rejections, of either type, rest on
the fact that a patent has been issued and later issuance of a
second patent will continue protection, beyond the date of
expiration of the first patent, of the very same invention
claimed therein (same invention type double patenting) or of a
mere variation of that invention which would have been
obvious to those of ordinary skill in the relevant art
(obviousness-type double patenting). In the latter case, there
must be some clear evidence to establish why the variation
would have been obvious which can properly qualify as “prior
art.”
In re Kaplan, 789 F.2d 1574, 1579-80 (Fed. Cir. 1986) (emphasis in
original).
Obviousness-type Double Patenting
We agree with the Examiner’s fact finding, statement of the rejection
and responses to Appellants’ arguments as set forth in the Answer. We find
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Application 11/212,109
that the Examiner has provided evidence to support a prima facie case of
obviousness-type double patenting. We provide the following additional
comment to the Examiner’s argument set forth in the Final Rejection and
Answer. The application in question has matured into the Boyer patent,
therefore, the provisional nature of the rejection is withdrawn and we treat
the rejection as an obviousness-type double patenting rejection.
Appellants admit that, “Claims 1-5, and 56, and 58 of U.S.
Application No. 10/895,985, which issued as claims 1-5 and 13 and 15 of
US Patent No. 8,637,553, are directed the compound of formula I and salts
thereof.” App. Br. 4. Appellants argue that
The subject matter of the claims herein are directed to solid
dispersions with specific pharmaceutically acceptable matrix agents
which are not obvious variants of the broad generic subject matter
defined by the claims in Application No. 10/895,985, which issued as
US Patent No. 8,637,553. There is no evidence or allegation the
claims of Application No. 10/895,985 and US Patent No. 8,637,5536,
provide direction that would lead one skilled in the art to the solid
dispersions claimed herein with the matrix agents specified. There is
also no evidence it would be obvious to try to form the solid
dispersions claimed from this broad generic disclosure.
App. Br. 5. Appellants further argue that
There is no evidence showing the secondary references teach that the
preparation of solid dispersions is routine and can be formed with all
active compounds, as suggested in the advisory action. There is also
no evidence the secondary references provide direction in how to
predict which pharmaceuticals will form solid dispersions or which
will provide advantages as solid dispersions. There is also no evidence
the solid dispersions formed by the secondary references contain
compounds which are analogous to the compounds of formula I and
salts thereof. One secondary reference, Hirose, is cited for disclosing
solid dispersions of compounds with some structural features of the
compound of formula I but these compounds are so structurally
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Application 11/212,109
distinct, there is no allegation or suggestion they are analogous to the
compound of formula I.
App. Br. 6. We are not persuaded. There is no question that Boyer teaches
the claimed compound of formula I. App. Br. 4; Final Act 4. The Examiner
cites the remaining references to show that,
the prior art teaches that solid dispersion formulations are commonly
used in the pharmaceutical industry in order to improve the solubility
and/or bioavailability of a large and diverse structural and biological
type of drugs.
At the time of the invention it would have been prima facie
obvious for a person of ordinary skill in the art to make a solid
dispersion of known active agents including the fluoro compound of
formula I disclosed in application # 0/895,985 in order to obtain a
better formulation with better oral bioavailability, thus resulting in the
practice of claims 1, 3-22 and 36-47 with a reasonable expectation of
success.
Final Act. 7.
While Appellants argue that there is no evidence showing that the
secondary references teach that the preparation of solid dispersions is routine
and can be formed with varying active compounds, we disagree. Leuner
teaches the advantages of using solid dispersions to address solubility issues
associated with drugs. Abstract. Aoki teaches that the creation of a solid
dispersion is of interest to improve the solubility of a slightly soluble
medicament, for example, nifedipine, phenytoin, nitrofurantoin,
benoxaprofen, griseofulvin, sulfathiazole, tacrolimus, piroxicam,
carbamazepine, phenacetin and cyclic GMP phosphodiesterase inhibitors.
114 and 8. “Juppo teaches a solid dispersion formulation of felodipine and
bicatulamide (see paragraphs [0033] and [0034]).” Final Act 6.
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Appel teaches solid dispersion formulation for an enormous variety of
drugs (see paragraph [0035]. Further, Appeal teaches that the drug
does not need to be a low solubility drug in order to benefit from the
invention, although low solubility drugs represent a preferred class for
use with the invention (see paragraph [0026]). Hirose teaches solid
dispersion formulations of compounds of formula I (see page 2), la
(page 4) and lb (page 5) which show some of the structural features of
compound I, like ureas and substituted pyridine rings, etc. Nakamichi
teaches new methods for producing solid dispersions (see abstract)
which includes the use of polyvinylpyrrolidone (see column 2, line
49-50) as one of the preferred polymers, an teaches an enormous
variety of drugs which include: antipyretic, analgesic, anti­
inflammatory, antiulcer, coronary vasodilators, antibiotics,
antimicrobials, antispasmodic, bronchodilators, diuretics, etc, (see
column 3, line 50 through column 5, line 48).
Finally, Riegelman teaches solid dispersion formulations in
general. In summary, the prior art teaches that solid dispersion
formulations are commonly used in the pharmaceutical industry in
order to improve the solubility and/or bioavailability of a large and
diverse structural and biological type of drugs.
Final Act. 6—7. Appel also teaches that that one class of drugs that will
benefit from solid dispersion formulations, are drugs with a clogP value of at
least 3.0 and preferable 4.0, a clogP which the Examiner alleges is similar to
that of the compound of formula I. Ans. 12-13, 18. The Examiner has
provided evidence to support a prima facie case of obviousness-type double
patenting and evidence that those of ordinary skill in the art at the time of the
present invention were able to routinely prepare diverse drugs in the form of
solid dispersions, and that the prior art suggest that compounds having
similar properties to the compound of formula I would benefit from being
prepared as a solid dispersion.
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Appellants argue that Leuner discloses dosing limitations and
manufacturing concerns when preparing solid dispersions. App. Br. 7-8.
Reply Br. 6-7. Appellants further argue that Craig2 and other of the cited
references also disclose manufacturing concerns and poor predictability of
solid dispersion behavior. App. Br. 10, Reply Br. 8-30. We have weighed
these disclosures against the multitude of successful preparations of solid
dispersions disclosed in the cited prior art using PVP, and have found that
the balance of the evidence supports the Examiner’s conclusion that the
preparation of solid dispersions using PVP is routine. We further agree with
the Examiner that Craig does not specifically disclose why numerous solid
dispersion which have been published never made it to market, and that they
may not have made it to market for reasons unrelated to the fact that they are
solid dispersions. Ans. 27.
The Appellants argue that, “the examples of the application illustrate
that these two polymers [polyvinylpyrrolidone (PVP) and hydroxypropyl
cellulose] provide solid dispersions which are effective drug delivery
systems for the compound of formula I. The compound of formula I is
shown to be highly soluble in both polymers.” App. Br. 11. Appellants
argue that the examples in the Specification provide evidence of unexpected
results. Id. More particularly, Appellants argue that
Tables 1 and 2 on pages 26 and 27 of the application show
significant improvements in bioavailability in animal models using a
solid dispersion of this invention with polyvinylpyrrolidone over
2 Craig, et al., “The mechanisms of drug release from solid dispersions in
water-soluble polymers,” International Journal of Pharmaceutics, 231,
(2002) p 131-144.
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Application 11/212,109
conventional formulations of a free base of a compound of formula I
and pharmaceutically acceptable salts of a compound of formula I.
App. Br. 12.
We have carefully reviewed Appellants’ proffered evidence of
unexpected results obtained from a formulation comprising a compound of
formula I, PVP, and crosscarmellose in accordance with Example 11 of the
Specification, as provided in Table 2 of the Specification, page 27, but are
not persuaded by it. Appellants’ evidence does not show that the improved
bioavailability results were unexpected in view of the disclosures Luener,
Seradjuddim, Aoki, Bateman, Appel, Hirose, Nakamichi and Riegelman.
Expected beneficial results are not evidence of nonobviousness. See In re
Skoner, 517 F.2d 947, 950 (CCPA 1975). Each of the cited references show
that the preparation of a pharmaceutical agent in the form of a solid
dispersion improves the solubility and bioavailability of the pharmaceutical
agent, and that it is beneficial that the formulation include PVP. Ans. 12-17.
Moreover, Appellants’ evidence of unexpected results is not
commensurate in scope with the claims. The claims are not limited to a
solid dispersion of a compound of formula I, PVP, and crosscarmellose3. “It
is well established that the objective evidence of nonobviousness must be
commensurate in scope with the claims.” In re Lindner, 457 F.2d 506, 508
(CCPA 1972). Furthermore, unexpected results must be between the
claimed invention and the closest prior art.” In re Fenn, 639 F.2d 762, 765
(CCPA 1981). Hirose, cited by the Examiner, shows a compound with some
3 Crosscarmellose is cross-linked carboxymethylcellulose.
https://en.wikipedia.org/wiki/Croscarmellose_sodium
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Application 11/212,109
of the structural features of compound 1 prepared as a solid dispersion
including hydroxyl propyl cellulose (HPC), and polyvinyl pyrrolidone
(PVP) (see paragraph [0024]). Ans. 7-8. Appellants provide no evidence of
unexpected results in view of the closest prior art, including compounds
such as that of Hirose. Claims 7-10, 12-16, 43 and 44 fall for the reasons of
record and for the same reasons as claim 1.
The obviousness-type double patenting rejection is affirmed for the
reasons of record.
CONCLUSION OF LAW
On balance we finds that the preponderance of the evidence of record
supports the Examiner’s obviousness-type double patent rejection, which is
affirmed for the reasons of record.
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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