`
`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
`Alexandria1 Virginia 22313- 1450
`www.uspto.gov
`
`APPLICATION NO.
`
`
`
`
`
` F ING DATE
`
`FIRST NAMED INVENTOR
`
`ATTORNEY DOCKET NO.
`
`
`
`
`
`CONF {MATION NO.
`
`13/579,796
`
`10/10/2012
`
`Jatin Patel
`
`03 822000060.
`
`2947
`
`02/28/2014
`7590
`5514
`FITZPATRICK CELLA HARPEMSCINTO
`1290 Avenue of the Americas
`NEW YORK, NY 10104-3 800
`
`BARHAM, BETHANY P
`
`ART UNIT
`
`1615
`
`MAIL DATE
`
`02/28/2014
`
`PAPER NUMBER
`
`DELIVERY MODE
`
`PAPER
`
`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.
`
`PTOL—90A (Rev. 04/07)
`
`

`

`
`Application No.
`Applicant(s)
`
` 13/579,796 PATEL ET AL.
`Examiner
`Art Unit
`AIA (First Inventorto File)
`Office Action Summary
`
`1615BETHANY BARHAM first“
`
`-- The MAILING DA TE of this communication appears on the cover sheet with the correspondence address --
`Period for Reply
`
`A SHORTENED STATUTORY PERIOD FOR REPLY IS SET TO EXPIRE 3 MONTHS FROM THE MAILING DATE OF
`THIS COMMUNICATION.
`Extensions of time may be available under the provisions of 37 CFR 1.136(a).
`after SIX (6) MONTHS from the mailing date of this communication.
`If NO period for reply is specified above, the maximum statutory period will apply and will expire SIX (6) MONTHS from the mailing date of this communication.
`Failure to reply within the set or extended period for reply will, by statute, cause the application to become ABANDONED (35 U.S.C. § 133).
`Any reply received by the Office later than three months after the mailing date of this communication, even if timely filed, may reduce any
`earned patent term adjustment. See 37 CFR 1.704(b).
`
`In no event, however, may a reply be timely filed
`
`-
`-
`
`Status
`
`1)IXI Responsive to communication(s) filed on 01/27/14.
`[I A declaration(s)/affidavit(s) under 37 CFR 1.130(b) was/were filed on
`
`2b)lX| This action is non-final.
`2a)I:| This action is FINAL.
`3)I:I An election was made by the applicant in response to a restriction requirement set forth during the interview on
`
`
`; the restriction requirement and election have been incorporated into this action.
`
`4)|:I Since this application is in condition for allowance except for formal matters, prosecution as to the merits is
`closed in accordance with the practice under EX parte Quay/e, 1935 CD. 11, 453 O.G. 213.
`
`Disposition of Claims*
`
`5)|XI Claim(s) 13 5-13 and 16-18 is/are pending in the application.
`5a) Of the above claim(s) 13 and 16-18 is/are withdrawn from consideration.
`6 III Claim s) _ is/are allowed.
`1,3 and 5- 12 is/are rejected.
`
`is/are objected to.
`
`
`
`are subject to restriction and/or election requirement.
`* If any claims have been determined allowable, you may be eligible to benefit from the Patent Prosecution Highway program at a
`
`participating intellectual property office for the corresponding application. For more information, please see
` S
`htt
`://www.usoto. ov/ atents/init events) .tv'index.‘
`
`
`
`, or send an inquiry to PPI1feedback©usgto.qov.
`
`Application Papers
`
`10)I:I The specification is objected to by the Examiner.
`11)|:I The drawing(s) filed on _ is/are: a)I:I accepted or b)I:I objected to by the Examiner.
`Applicant may not request that any objection to the drawing(s) be held in abeyance. See 37 CFR 1.85(a).
`
`Replacement drawing sheet(s) including the correction is required if the drawing(s) is objected to. See 37 CFR 1.121 (d).
`
`Priority under 35 U.S.C. § 119
`12)I:I Acknowledgment is made of a claim for foreign priority under 35 U.S.C. §119(a)-(d) or (f).
`Certified copies:
`
`b)I:I Some” c)I:I None of the:
`a)I:I All
`1.|:| Certified copies of the priority documents have been received.
`2.|:| Certified copies of the priority documents have been received in Application No.
`3.I:I Copies of the certified copies of the priority documents have been received in this National Stage
`
`application from the International Bureau (PCT Rule 17.2(a)).
`** See the attached detailed Office action for a list of the certified copies not received.
`
`Attachment(s)
`
`
`
`3) D Interview Summary (PT0_413)
`1) E Notice of References Cited (PTO-892)
`Paper No(s)/Mai| Date.
`.
`.
`—
`4) I:I Other'
`2) E Information Disclosure Statement(s) (PTO/SB/08a and/or PTO/SB/08b)
`
`Paper No(s)/Mai| Date .
`U.S. Patent and Trademark Office
`PTOL-326 (Rev. 11-13)
`
`Office Action Summary
`
`Part of Paper No./Mai| Date 20140219
`
`

`

`Application/Control Number: 13/579,796
`
`Page 2
`
`Art Unit: 1615
`
`DETAILED ACTION
`
`Summary
`
`The present application is being examined under the pre-AIA first to invent
`
`provisions. Receipt of the multiple lDSs filed is acknowledged. Receipt of the Claim
`
`Amendments and Response filed on 01/27/14 is also acknowledged. Claims 1, 3, 5-13
`
`and 16-18 are pending.
`
`Election/Restrictions
`
`Applicant's election with traverse of Group in the reply filed on 01/27/14 is
`
`acknowledged. The traversal is on the ground(s) that a single special technical feature
`
`now claimed is not taught by US 2006/0160841. This is not found persuasive because
`
`the claims as originally presented lack a special technical feature and Groups l-Vl differ
`
`in scope and have different modes of operation, effects, and functions. Specifically, as
`
`pointed out in the 10/29/13 Election/Restriction requirement, Group | and Group II have
`
`different sizes and as such the common technical feature is "[a] composition comprising
`
`crystalline apixaban particles and a pharmaceutically acceptable diluent or carrier" and
`
`secondly this common technical feature is known in the art as evidenced by at least US
`
`2006/0160841 which teaches a slurry of PG and water comprising N-1 form of apixaban
`
`particles of D90 of less than 20 microns (see Examples). As such, claims 13 and 16-18
`
`are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn
`
`to a nonelected species and invention, there being no allowable generic or linking claim.
`
`

`

`Application/Control Number: 13/579,796
`
`Page 3
`
`Art Unit: 1615
`
`Claims 1, 3, and 5-12 will be examined in the instant application. Applicant timely
`
`traversed the restriction (election) requirement in the reply filed on 01/27/14. The
`
`requirement is still deemed proper and is therefore made FINAL.
`
`Priority- Claim Rejections - 35 USC § 1 12
`
`Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e)
`
`or under 35 U.S.C. 120, 121, or 365(c) is acknowledged. Applicant has not complied
`
`with one or more conditions for receiving the benefit of an earlier filing date under 35
`
`U.S.C. 119(e) as follows:
`
`The later-filed application must be an application for a patent for an invention
`
`which is also disclosed in the prior application (the parent or original nonprovisional
`
`application or provisional application). The disclosure of the invention in the parent
`
`application and in the later-filed application must be sufficient to comply with the
`
`requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AlA 35 U.S.C. 112,
`
`except for the best mode requirement. See Transco Products, Inc. v. Performance
`
`Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
`
`The disclosure of the prior-filed application, Application No. 61/308056, fails to
`
`provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or
`
`pre-AlA 35 U.S.C. 112, first paragraph for one or more claims of this application. There
`
`is no support for “D90 equal to or less than about 89 pm” of claim 1 from which all other
`
`claims depends.
`
`

`

`Application/Control Number: 13/579,796
`
`Page 4
`
`Art Unit: 1615
`
`As such the priority of claim 1 and dependent claims thereon is the filing date of
`
`the instant application.
`
`NEW-Claim Rejections - 35 USC § 1 12
`
`The following is a quotation of 35 U.S.C. 112(a):
`(a) IN GEN ERAL.—The specification shall contain a written description of the invention, and of the
`manner and process of making and using it, in such full, clear, concise, and exact terms as to enable
`any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and
`use the same, and shall set forth the best mode contemplated by the inventor orjoint inventor of
`carrying out the invention.
`
`The following is a quotation of 35 U.S.C. 112 (pre-AIA), first paragraph:
`The specification shall contain a written description of the invention, and of the manner and process of
`making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the
`art to which it pertains, or with which it is most nearly connected, to make and use the same and shall
`set forth the best mode contemplated by the inventor of carrying out his invention.
`
`Claims 9-10 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA), first
`
`paragraph, as failing to comply with the written description requirement. The claim(s)
`
`contains subject matter which was not described in the specification in such a way as to
`
`reasonably convey to one skilled in the relevant art that the inventor or a joint inventor,
`
`or for pre-AIA the inventor(s), at the time the application was filed, had possession of
`
`the claimed invention. The instant claims claim functional language without any actual
`
`structure. The claims claim AUC and/or Cmax that is at least 80% of the mean AUC
`
`and/or Cmax observed for an equivalent formulation differing only in that the D90 is
`
`89microns which has to do with the specific structural components in the composition
`
`i.e. excipients like specific granulating agents such as microcrystalline cellulose,
`
`lubricants, etc. such as those in instant Tables 3-5, but such functional limitations of
`
`

`

`Application/Control Number: 13/579,796
`
`Page 5
`
`Art Unit: 1615
`
`AUC/Cmax, etc. in the absence of such structure limitations % cellulose, type of
`
`lubricant, etc. do not further limit the structure of the instant claims. This is a written
`
`description rejection.
`
`For the purpose of prior art any composition that contains apixaban and a
`
`pharmaceutically acceptable diluent or carrier, wherein the apixaban particles which are
`
`crystalline and have a D90 of less than about 89microns meets the functional limitations
`
`of AUC/Cmax in instant claims 9-10.
`
`Claim Rejections - 35 USC § 102
`The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that
`
`form the basis for the rejections under this section made in this Office action:
`
`A person shall be entitled to a patent unless —
`
`(a) the invention was known or used by others in this country, or patented or described in a printed
`publication in this or a foreign country, before the invention thereof by the applicant for a patent.
`
`(b) the invention was patented or described in a printed publication in this or a foreign country or in public
`use or on sale in this country, more than one year prior to the date of application for patent in the United
`States.
`
`(e) the invention was described in (1) an application for patent, published under section 122(b), by
`another filed in the United States before the invention by the applicant for patent or (2) a patent
`granted on an application for patent by another filed in the United States before the invention by the
`applicant for patent, except that an international application filed under the treaty defined in section
`351 (a) shall have the effects for purposes of this subsection of an application filed in the United States
`only if the international application designated the United States and was published under Article 21(2)
`of such treaty in the English language.
`
`Claims 1, 3, and 5-10 are rejected under 35 U.S.C. 102(a) as being anticipated
`
`by US 2006/016841 ('841).
`
`.
`
`‘841 teaches apixaban particles which are crystalline and have a D90 of less than
`
`about 20microns which are then washed with water Examples 1-3, meeting the
`
`limitations of the instant claims 1, 5-8.
`
`

`

`Application/Control Number: 13/579,796
`
`Page 6
`
`Art Unit: 1615
`
`.
`
`‘841 teaches that the composition has the N-1 form of apixaban in Examples 1-3,
`
`according to the limitations of instant claim 3.
`
`0 With regard to claims 9-10 which are directed to a release profile, since the
`
`composition is the same (i.e. apixaban crystalline particles of D90 of less than
`
`about 20microns in a pharmaceutically acceptable carrier (water)) then the
`
`release profile, AUC and/or Cmax would naturally be the same since a product is
`
`not separable from its physical properties.
`
`Claim Rejections - 35 USC § 103
`
`The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all
`
`obviousness rejections set forth in this Office action:
`
`(a) A patent may not be obtained though the invention is not identically disclosed or described as set
`forth in section 102 of this title, if the differences between the subject matter sought to be patented and
`the prior art are such that the subject matter as a whole would have been obvious at the time the
`invention was made to a person having ordinary skill in the art to which said subject matter pertains.
`Patentability shall not be negatived by the manner in which the invention was made.
`
`Claims 1, 3, and 5-12 are rejected under 35 U.S.C. 103(a) as being unpatentable
`
`over US 2006/016841 ('841) in view of US 2012/0087978 (‘978) (which has priority to
`
`06/16/09).
`
`.
`
`0
`
`‘841 is taught above.
`
`‘841 does not teach formulations with surfactants such as SLS, but does teach
`
`crystalline apixaban with D90 less than 20microns dispersed in water.
`
`

`

`Application/Control Number: 13/579,796
`
`Page 7
`
`Art Unit: 1615
`
`.
`
`‘978 claims a dosage form comprising solubility improved apixaban such as
`
`crystalline forms and according to ‘978 apixaban formulations of diameter of
`
`900nm or less are formulated a stabilization aid such as a surfactant and
`
`discloses that sodium lauryl sulfate (SL8) is a known surfactant ([0066, 0149],
`
`claims 1 and 6; Ex. 7 Table 8).
`
`It would have been obvious to one of ordinary skill in the art at the time the invention
`
`was made to combine ‘841 with ‘978. The combination of a known particulate
`
`crystalline apixaban product of ‘841 with a known technique of formulating apixaban in
`
`particulate crystalline forms with surfactants such as SL8 for a similar purpose of
`
`improved apixaban is within the purview of the skilled artisan and would yield
`
`predictable results. The skilled artisan would know how to combine of a known product
`
`with a known technique for a similar purpose with predictable results.
`
`Claims 1, 3, and 5-11 are rejected under 35 U.S.C. 103(a) as being unpatentable
`
`over US 2010/003811 (‘811).
`
`.
`
`‘811 teaches modification of a bio-active substance such as axipaban with an
`
`amphiphilic protein (a surfactant), such that it reduces the crystallite size to 5-
`
`5000nm, especially 2—2000nm and that such a reduction in crystal size is known
`
`to improve bioavailability or dissolution (abstract, pg. 1, lines 6-20; pg. 5, lines 5-
`
`18; pg. 12, lines 20; claim 14).
`
`0 With regard to claims 9-10 which are directed to a release profile, since the
`
`composition is the same (i.e. apixaban crystalline particles of D90 of less than
`
`

`

`Application/Control Number: 13/579,796
`
`Page 8
`
`Art Unit: 1615
`
`about 89 microns in a surfactant) then the release profile, AUC and/or Cmax
`
`would naturally be the same since a product is not separable from its physical
`
`properties.
`
`.
`
`‘811 does not teach a specific example with axipaban.
`
`A reference is analyzed using its broadest teachings. MPEP 2123 [R-5].
`
`“[W]hen a patent simply arranges old elements with each performing the same
`
`function it had been known to perform and yields no more than one would expect from
`
`such an arrangement, the combination is obvious”. KSR v. Teleflex, 127 S,Ct. 1727,
`
`1740 (2007)(quoting Sakraida v. A.G. Pro, 425 US. 273, 282 (1976). “[W]hen the
`
`question is whether a patent claiming the combination of elements of prior art is
`
`obvious”, the relevant question is “whether the improvement is more than the
`
`predictable use of prior art elements according to their established functions.” (ld_.).
`
`Addressing the issue of obviousness, the Supreme Court noted that the analysis under
`
`35 USC 103 “need not seek out precise teachings directed to the specific subject matter
`
`of the challenged claim, for a court can take account of the inferences and creative
`
`steps that a person of ordinary skill in the art would employ.” KSR v. Teleflex, 127 S.Ct.
`
`1727, 1741 (2007). The Court emphasized that “[a] person of ordinary skill is... a person
`
`of ordinary creativity, not an automaton.” |d_. at 1742.
`
`It would have been obvious to one of ordinary skill in the art at the time the
`
`invention was made to rearrange the disclosed Examples and modify axipaban a
`
`disclosed bioactive of ‘811 with an amphiphilic protein (a surfactant), such that it
`
`

`

`Application/Control Number: 13/579,796
`
`Page 9
`
`Art Unit: 1615
`
`reduces the crystallite size to 5-5000nm, especially 2—2000nm and that such a reduction
`
`in crystal size is known to improve bioavailability or dissolution with predictable results.
`
`Claims 1, 3, and 5-12 are rejected under 35 U.S.C. 103(a) as being unpatentable
`
`over US 2010/003811 (‘81 1) in View of US 2009/0285887 (‘887).
`
`.
`
`.
`
`.
`
`‘811 is taught above.
`
`‘811 does not teach other surfactants other than the amphiphilic protein.
`
`‘887 teaches known surfactants include SLS [0051].
`
`It would have been obvious to one of ordinary skill in the art at the time the invention
`
`was made to combine ‘811 with ‘887. The simple substitution of the surfactant of ‘811
`
`with surfactants such as SLS of ‘887 would yield predictable results. The skilled artisan
`
`would know how to one surfactant for another with predictable results.
`
`Claims 1, 3, and 5-12 are rejected under 35 U.S.C. 103(a) as being unpatentable
`
`over US 2010/003811 (‘81 1) in view of US 2012/0087978 (‘978) (which has priority to
`
`06/16/09).
`
`.
`
`.
`
`.
`
`‘811 is taught above.
`
`‘811 does not teach other surfactants other than the amphiphilic protein.
`
`‘978 claims a dosage form comprising solubility improved apixaban such as
`
`crystalline forms and according to ‘978 apixaban formulations of diameter of
`
`900nm or less are formulated a stabilization aid such as a surfactant and
`
`

`

`Application/Control Number: 13/579,796
`
`Page 10
`
`Art Unit: 1615
`
`discloses that sodium lauryl sulfate (SLS) is a known surfactant ([0066, 0149],
`
`claims 1 and 6; Ex. 7 Table 8).
`
`It would have been obvious to one of ordinary skill in the art at the time the invention
`
`was made to combine ‘811 with ‘978. The combination of a known particulate
`
`crystalline apixaban product of ‘811 with a known technique of formulating apixaban in
`
`particulate crystalline forms with specific surfactants such as SLS for a similar purpose
`
`of improved apixaban is within the purview of the skilled artisan and would yield
`
`predictable results. The skilled artisan would know how to combine of a known product
`
`with a known technique for a similar purpose with predictable results.
`
`Correspondence
`
`Any inquiry concerning this communication or earlier communications from the
`
`examiner should be directed to Bethany Barham whose telephone number is (571 )-272—
`
`6175. The examiner can normally be reached on Monday to Friday; 8:30 am. to 5:00
`
`pm. EST.
`
`If attempts to reach the examiner by telephone are unsuccessful, the examiner’s
`
`supervisor, Robert A. Wax can be reached on (571)272-0623. The fax phone number
`
`for the organization where this application or proceeding is assigned is 571 -273-8300.
`
`

`

`Application/Control Number: 13/579,796
`
`Page 11
`
`Art Unit: 1615
`
`Information regarding the status of an application may be obtained from the
`
`Patent Application Information Retrieval (PAIR) system. Status information for
`
`published applications may be obtained from either Private PAIR or Public PAIR.
`
`Status information for unpublished applications is available through Private PAIR only.
`
`For more information about the PAIR system, see http://pair-direct.uspto.gov. Should
`
`you have questions on access to the Private PAIR system, contact the Electronic
`
`Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a
`
`USPTO Customer Service Representative or access to the automated information
`
`system, call 800-786-9199 (IN USA OR CANADA) or 571 -272-1000.
`
`/BETHANY BARHAM/
`
`Primary Examiner, Art Unit 1615
`
`