`
`Attorney Docket No. 112850056-00000
`
`PATENT
`
`tn re Application of:
`
`John Ft. Evans et al.
`
`Application No.: 12f285,887
`
`Filed: October15,2008
`
`For:
`
`FORMULATION
`
`Commissioner for Patents
`PO. Box 1450
`
`Alexandria, VA 22313-1450
`
`Sir:
`
`--4--J\—..u\-...v-—a-./-—.a-_—-5;
`
`Group Art Unit: 1628
`
`Examiner: HUI, San Ming Ft.
`
`Confirmation No.: 1199
`
`VIA EFS-WEB
`
`RESPONSE AND AMENDMENT UNDER 37 C.F.FI. § 1.111 AND
`PETITION FOFI EXTENSION OF TIME
`
`in reply to the non-final Office Action mailed December 21, 2010 (“Office Action”),
`
`and pursuant to 37 C.F.Fi. § 1.111, Applicants hereby respectfully request
`
`reconsideration of this application in View of the following amendments and remarks.
`
`Applicants hereby petition for a three-month extension of time to respond to the Office
`
`Action. The requisite tee is being paid concurrently with this Response.
`
`Amendments to the Claims are reflected in the listing of claims, which starts on
`
`page 2 of this paper. Remarks follow the amendment sections of this paper and start
`
`on page 9.
`
`Astrazeneca Ex. 2142 p. 1
`Mylan Pharms. Inc. V. AstraZeneca AB IPR2016-01324
`
`
`
`Application No; 12!285.B87
`Attorney Docket No.: 112850056-00000
`
`AMENDMENTS TO THE CLAIMS
`
`Please add new claims 24-53. Please also cancel claims 1-23 without prejudice
`
`or disclaimer. This listing of claims will replace all prior versions and listings of claims in
`
`the application.
`
`Claims 1-23 (Cancelled)
`
`24.
`
`(New) A method for treating a hormonal dependent benign or malignant disease
`
`of the breast or reproductive tract comprising administering intramuscularly to a
`
`human in need of such treatment a formulation comprising:
`
`at least 45 mgml" of fulvestrant;
`
`a mixture of from 17 — 23% w/v of ethanol and benzyl alcohol;
`
`12 - 13% w/v of benzyl benzoate; and
`
`a sufficient amount of castor oil vehicle;
`
`wherein the method achieves a therapeutically significant blood plasma
`
`fulvestrant concentration of at least 2.5 ngml" for at least two weeks.
`
`25.
`
`(New) The method of claim 24, wherein the ethanol and benzyl alcohol are
`
`present in the same weight./volume amounts.
`
`26.
`
`(New) The method of claim 24, wherein the therapeutically significant blood
`
`plasma fulvestrant concentration is at least 8.5 ngml'1.
`
`27.
`
`(New) The method of claim 24, wherein the hormonal dependent benign or
`
`malignant disease of the breast or reproductive tract is breast cancer.
`
`Astrazeneca Ex. 2142 p. 2
`
`
`
`Application No.: 12/285,887
`Attorney Docket No.: ‘l1285.0056-00000
`
`(New) The method of claim 24, wherein the therapeutically significant blood
`
`plasma fulvestrant concentration is attained for at least 4 weeks.
`
`(New) The method of claim 24, wherein the method comprises administering
`
`intramuscularly to a human in need of such treatment 5 mL of the formulation.
`
`(New) The method of claim 24, wherein the method further comprises once
`
`monthly administration of the formulation.
`
`(New) The method of claim 24, wherein the formulation comprises:
`
`about 50 mgmi" of fulvestrant;
`
`about 10% w/v of ethanol;
`
`about 10% wfv of benzyl alcohol; and
`
`about 15% w/v of benzyl benzoate;
`
`wherein the therapeutically significant blood plasma fulvestrant concentration is
`
`at least 8.5 ngml".
`
`(New) The method of claim 31, wherein the hormonal dependent benign or
`
`malignant disease of the breast or reproductive tract is breast cancer.
`
`(New) The method of claim 32, wherein the therapeutically significant blood
`
`plasma fulvestrant concentration is attained for at least 4 weeks.
`
`(New) The method of claim 33, wherein the method comprises administering
`
`intramuscularly to a human in need of such treatment 5 mL of the formulation.
`
`28.
`
`29.
`
`30.
`
`31.
`
`32.
`
`33.
`
`34.
`
`Astrazeneca Ex. 2142 p. 3
`
`
`
`Application No.: 12/285,887
`Attorney Docket No.: 112850056-00000
`
`35.
`
`36.
`
`37.
`
`38.
`
`39.
`
`40.
`
`(New) The method of claim 34, wherein the method further comprises once
`
`monthly administration of the formulation.
`
`(New) A method for treating a hormonal dependent benign or malignant disease
`
`of the breast or reproductive tract comprising administering intramuscularly to a
`
`human in need of such treatment a formulation consisting essentially of:
`
`at least 45 mgml" of fulvestrant;
`
`a mixture of from 17 — 23% w/v of ethanol and benzyl alcohol;
`
`12 - 18% w/v of benzyl benzoate; and
`
`a sufficient amount of castor oil vehicle;
`
`wherein the method achieves a therapeutically significant blood plasma
`
`fulvestrant concentration of at least 2.5 ngml" for at least two weeks.
`
`(New) The method of claim 36, wherein the ethanol and benzyl alcohol are
`
`present in the same weight/volume amounts.
`
`(New) The method of claim 36, wherein the therapeutically significant blood
`
`plasma fulvestrant concentration is at least 8.5 ngml".
`
`(New) The method of claim 36, wherein the hormonal dependent benign or
`
`malignant disease of the breast or reproductive tract is breast cancer.
`
`(New) The method of claim 36, wherein the therapeutically significant blood
`
`plasma fulvestrant concentration is attained for at least 4 weeks.
`
`Astrazeneca Ex. 2142 p. 4
`
`
`
`Application No.: 12/285,887
`Attorney Docket No.: 1 12850056-00000
`
`(New) The method of claim 36, wherein the method comprises administering
`
`intramuscularly to a human in need of such treatment 5 mL of the formulation.
`
`(New) The method of claim 36, wherein the method further comprises once
`
`monthly administration of the formulation.
`
`(New) The method of claim 36, wherein the formulation consists essentially of:
`
`about 50 mgml" oi fulvestrant;
`
`about 10% w/V of ethanol;
`
`about 10% w/v of benzyl alcohol; and
`
`about 15% will of benzyl benzoate;
`
`wherein the therapeutically significant blood plasma fulvestrant concentration is
`
`at least 8.5 ngml”.
`
`(New) The method of claim 43, wherein the hormonal dependent benign or
`
`malignant disease of the breast or reproductive tract is breast cancer.
`
`(New) The method of claim 44, wherein the therapeutically significant blood
`
`plasma fulvestrant concentration is attained for at least 4 weeks.
`
`(New) The method of claim 45, wherein the method comprises administering
`
`intramusoularly to a human in need of such treatment 5 mL of the formulation.
`
`(New) The method of claim 46, wherein the method further comprises once
`
`monthly administration of the formulation.
`
`41.
`
`42.
`
`43.
`
`44.
`
`45.
`
`46.
`
`47.
`
`Astrazeneca Ex. 2142 p. 5
`
`
`
`Application No.: 12f285,BB7
`Attorney Docket No.: 11285.0056—0O000
`
`48.
`
`(New) A method for treating a hormonal dependent benign or malignant disease
`
`of the breast or reproductive tract comprising administering intramuscularly to a
`
`human in need of such treatment 5 — 5.25 mL of a formulation comprising:
`
`4 - 6% w/V of fulvestrant;
`
`a mixture of from 17 — 23% w/v of ethanol and benzyl alcohol;
`
`12 - 18% wlv of benzyl benzoate; and
`
`a sufficient amount of castor oil vehicle;
`
`wherein the method achieves a therapeutically significant blood plasma
`
`fulvestrant concentration of at least 2.5 ngml" for at least two weeks.
`
`49.
`
`(New) A method for treating a hormonal dependent benign or malignant disease
`
`of the breast or reproductive tract comprising monthly intramuscular
`
`administration to a human in need of such treatment of a formulation comprising:
`
`4 - 6% w/v of fulvestrant;
`
`a mixture of from 17 — 23% w/v of ethanol and benzyl alcohol;
`
`12 - 18% wlv of benzyl benzoate; and
`
`a sufficient amount of castor oil vehicle;
`
`wherein the method achieves a therapeutically significant blood plasma
`
`fulvestrant concentration of at least 2.5 ngml” for at least two weeks.
`
`50.
`
`(New) A method for treating a hormonal dependent benign or malignant disease
`
`of the breast or reproductive tract comprising monthly intramuscular
`
`administration to a human in need of such treatment of a formulation comprising:
`
`4 - 6% w/v of fulvestrant;
`
`Astrazeneca Ex. 2142 p. 6
`
`
`
`Application No.: 12/285,887
`Attorney Docket No.: 11285.0056—D0000
`
`a mixture of from 17 — 23% w/v of ethanol and benzyl alcohol;
`
`12 - 18% w/v of benzyl benzoate; and
`
`a sufficient amount of castor oil vehicle;
`
`wherein the formulation is administered in a divided dose; and
`
`wherein the method achieves a therapeutically significant blood plasma
`
`fulvestrant concentration of at least 2.5 ngml" for at least two weeks.
`
`51.
`
`(New) A method for treating a hormonal dependent benign or malignant disease
`
`of the breast or reproductive tract comprising administering intramuscularly to a
`
`human in need of such treatment 5 — 5.25 mL of a formulation consisting
`
`essentially of:
`
`4 — 6% w/V of fulvestrant;
`
`a mixture of from 17 — 23% w/v of ethanol and benzyl alcohol;
`
`12 — 18% wfv of benzyl benzoate; and
`
`a sufficient amount of castor oil vehicle;
`
`wherein the method achieves a therapeutically significant blood plasma
`
`fulvestrant concentration of at least 2.5 ngml" for at least two weeks.
`
`52.
`
`(New) A method for treating a hormonal dependent benign or malignant disease
`
`of the breast or reproductive tract comprising monthly intramuscular
`
`administration to a human in need of such treatment of a formulation consisting
`
`essentially of:
`
`4 - 6% w/v of fulvestrant;
`
`a mixture of from 17 — 23% w/v of ethanol and benzyl alcohol;
`
`Astrazeneca Ex. 2142 p. 7
`
`
`
`Application No.: 12/285,887
`Attorney Docket No.: 112850056-00000
`
`12 - 18% w/v of benzyl benzoate; and
`
`a sufficient amount of castor oil vehicle;
`
`wherein the method achieves a therapeutically significant blood plasma
`
`fulvestrant concentration of at least 2.5 ngml" for at least two weeks.
`
`53.
`
`(New) A method for treating a hormonal dependent benign or malignant disease
`
`of the breast or reproductive tract comprising monthly intramuscular
`
`administration to a human in need of such treatment of a fonnulation consisting
`
`essentially of:
`
`4 - 6% w/v of fulvestrant;
`
`a mixture of from 17 — 23% w/v of ethanol and benzyl alcohol;
`
`12 - 18% w/v of benzyl benzoate; and
`
`a sufficient amount of castor oil vehicle;
`
`wherein the fomtulation is administered in a divided dose; and
`
`wherein the method achieves a therapeutically significant blood plasma
`
`fulvestrant concentration of at least 2.5 ngml" for at least two weeks.
`
`Astrazeneca Ex. 2142 p. 8
`
`
`
`Application No.: 12285.88?
`Attorney Docket No; ‘i'i285.0056-«D0000
`
`L
`
`Status of the ciaims and amendments
`
`REMARKS
`
`Upon entry of the instant amendments, claims 24-53 wiii be pending in this
`
`appiioation. Cieims 1-23 are being oenoeiieci in this Response without preiudice or
`
`disclaimer. New oieime 24-53 are being added in this Response. Claims 24-35 and
`
`48-50 are directed to methods for treating a hormonei dependent benign or malignant
`
`disease of the breast or reproductive tree’: comprising administering intremuscuieriy ‘to a
`
`human in need of such treatment a formulation comprising various components. Ciaims
`
`35-4? and 51-53 are identical to ciaims 24-35 and 48-50 except that the phrase
`
`“formulation consisting essentieriy of’ replaces the phrase “fonnuiation eompfising’ ihe
`
`various components.
`
`New claim 24 finds support, for example, in original oieim 21. The recitation in
`
`claim 2:!» regarding “at ieaet 45 mg mi” of fuivestrent” finds support, for example, in the
`
`specification at 1: M1283.’ The recitation regarding “a mixture of from 1? - 23% wiv of
`
`ethane! and benzyi eieohoi” finds support, for exampie, in the specification at ‘MI {(3035},
`
`{B036}, and {G042}. The recitation regarding “12 »~ 18% wfv of benzyi benzoate“ finds
`
`support, for exempie, in the specification at 111] [0040] and {D042}. The recitation
`
`regarding “a sufficient amount of caster oi! xrehicie” finds support, for exempie, in the
`
`specification at 11 {(3027}. The recitation regarciing “a therepeuticeily significant blood
`
`1 Uraiess otherwise specifieci, ail citations to the instant specification refer to the
`pagination from the published eppiieetiori US 2010/0152149.
`
`Astrazeneca Ex. 2142 p. 9
`
`
`
`Application No: 12f285,B3‘7
`Attorney Docket No: 112853056-00000
`
`plasma fulvestrant concentration of at least 2.5 ngml" for at least two weeks” finds
`
`support, for example, in the specification at mi [0027] and {Q1351}.
`
`New claim 25 finds support, for example, in the specification ei1l[DD36]. New
`
`claim 26» finds support, for example. in the specification at ‘F; [GU51]. New ciaim 2'7 lincis
`
`support, for example, in the speoifioetien at ‘ll {G064}. New oiaim 28 finds support, for
`
`example, in the specification at ‘il 10052]. New claim 29 lines support, for example, in
`
`the specification at ‘ii [G063]. New claim 1'-ifltinds support, for example, in the
`
`specification at ‘ll {D023}! New claim 31 finds support, for example, in the specification
`
`at '11 {B053} end the “Formuiation Example” (e.g., ‘ml [@072] to [D{}7S}). Mew claim 32
`
`finds support, for example, in the specification at ‘ll [$064]. New ciaim 33 finds support,
`
`for example, in the specification at ‘fl {£3052}. New oiaim 34 time support, for example}
`
`in the specification at1l E0063]. New claim 35 finds support, for example, in the
`
`specification at ‘B [D023].
`
`Claims 43-50 share various iimitations with claim 24, for which support has been
`
`identified above. The recitation in claim 48 regarding administration of “.5 —~ 5.25 mL” of
`
`formulation finals support, for example, in the specification et1l{flD34]. The recitation in
`
`claim 48 regarding “4 - 6% WW of iulvestrehf’ finds support, for example, in the
`
`specification at11[D025}. The recitation in claim 49 regarding “monthly intramuscular
`
`aciministration" finds support, for exampie, in the specification at'1l [D023]. The
`
`recitation in cieim Si} regatrciing “the formulation [being] administered in a divided dose”
`
`finds support, for exempts, in the specification at ‘it [0053].
`
`Beoeuse oieims 36-4? and 51-53 are identical to cieims24-35 end 48-50 except
`
`for the transitional phrase (“consisting essentialiy oi” instead of “oomprising”), the same
`
`-19..
`
`Astrazeneca EX. 2142 p. 10
`
`
`
`Application No.: 12/285,887
`Attorney Docket No.: 112850056-00000
`
`disclosure from the instant specification cited above for claims 24—35 and 48-50
`
`provides support for claims 36-47 and 51-53. The instant amendments do not add new
`
`matter.
`
`ll. Rejection under 35 U.S.C. § 103
`
`The Office rejected claims 1-23 under 35 U.S.C. § 103(a) as being unpatentable
`
`over European Patent Specification No. EP 0 346 014 (“Dukes”) in view of US Reissue
`
`Patent No. 28,690 (“Lehman.n"), Great Britain Patent Specification No. GB 1 569 286
`
`(“GB 1 569 286"), Osborne et at, Journal of National Cancer Institute, 87(10):746—750
`
`(1995) (“Osborne”), and Remington's Pharmaceutical Sciences, 18”‘ ed., p. 219 (1990)
`
`(“ Remington") .
`
`Applicants cancelled claims 1-23 in the instant Response. Thus, this rejection is
`
`now moot. However, in an effort to advance prosecution, and to the extent that the
`
`Office is considering applying the arguments from the outstanding obviousness rejection
`
`to the newly added claims, Applicants will address the rejections in the Office Action
`
`below.
`
`According to the Office, Dukes teaches that “antiestrogen agents, including
`
`fulvestrant, are useful in treating postmenopausal symptoms such as urogenital atrophy
`
`affecting the vagina." Office Action at 3. The Office further argues that Dukes “teaches
`
`that antiestrogen agent, including fulvestrant, may be used in a dosage of 50mg to 5g in
`
`vehicle comprising Castor oil and benzyl alcohol." id. The Office acknowledges,
`
`however, that among other deficiencies, Dukes “does not expressiy teach the
`
`employment of benzyl benzoate .
`
`.
`
`. as part of the vehicle herein.” Id.
`
`-11-
`
`AstraZeneca Ex. 2142 p. 11
`
`
`
`Application No.: t2f285.837
`Attorney Docket No.: 1‘l285.0056—00OO0
`
`in an attempt to cure the shortcomings in Dukes, the Office cites Lehmann as
`
`teaching "that benzyl benzoate and castor oil are well-known solvent useful as
`
`conventional carriers for steroids." Office Action at 3.
`
`In the Office's view GB 1 569 286
`
`“teaches an intramuscular injection of testosterone derivative containing castor
`
`oil/benzoate in a ratio of 6:4” (id.); Osborne “teaches fulvestrant as useful in treating
`
`human breast cancer’ (id. at 4); and Remington teaches “that ethanol is one of the most
`
`commonly used solvents in pharmaceutical industry” (id.).
`
`The Office concludes that:
`
`One of ordinary skill in the art would have been motivated to employ
`benzyl benzoate, ethanol, castor oil, and benzyl alcohol, in the herein
`claimed weight percent, with fulvestrant, in the dosage herein, in a method
`of treating postmenopausal symptoms such as urogenital atrophy or
`treating breast cancer because fulvestrant is known to be useful in treating
`urogenital atrophy, a benign disease of the female reproductive tract in the
`vagina and breast cancer.
`
`Office Action at 4. According to the Office:
`
`[C]ombining one or more agents, which are known to be useful as
`commonly used solvents, such as benzyl benzoate, ethanol, castor oil,
`and benzyl alcohol, together and incorporated such combination with an
`estrogen derivatives, fulvestrant, would be reasonably expected to be
`useful in formulating a phannaceutical composition.
`
`Office Action at 4. The Office further argues that “the optimization of result
`
`effect[ive] parameters (e.g., amount of excipients, dosage range, and dosing
`
`regimens) is obvious as being within the skill of the artisan, absent evidence to
`
`the contrary.” id. at 5. Applicants respectfully traverse this rejection.
`
`-12-
`
`AstraZeneca Ex. 2142 p. 12
`
`
`
`Application i~lo.: 12/285,88?
`Attorney Docket No: 11285.{3056—0O00O
`
`ILA One of ordinary skill in the art would not have oomblned the cited
`raforoneos in the manner proposed in the rejection
`
`The Office relies on Dukes to argue that formulations comprising fuiveotrant “in a
`
`dosage of 50mg to 59 in vehicle oomprising oaslror oi! and benzyl aioohof’ were known
`
`in the art. Office Action at 3. The filifiioe than states that one of ordinary skiii in the art
`
`would have added ethanol and boozy! benzoaie. to Dukes formuiation to arrive at the
`
`formuiaiion recited in the claims.
`
`id. The Office, however, provides no explanation for
`
`why one of ordinary skill in the an wouici have modified Dukes formuiatiors in the
`
`proposed manner. As will be expiaineci oeiow, one of ordinary skill in the art would not
`
`have modified Dukes formulation at least because the addition of boozy! bonzoate
`
`wouicl have been expeoieo to reduce the soluoiiity of iulvestrant in the iormuiation.
`
`Because fulvootrani is difficult to iorrnoiate, one of ordinary skili in tho art wooid not
`
`have preparoo a formutation in which fuivestrant was expected to have a tower solubility
`
`than that in the initial formulation. See, o.g., specification at1i[0{)14}.
`
`The passage from Dukes cited by the Qriioe as diooiosing foivestrant
`
`formuiaiions indicates that when administering a pure anfrostrogen by periodic
`
`intramusoularl inieoiion, an oily soiotion of the pure antiostrogen “containing arachis or
`
`oastor oii Land] on alcohol such as bonzyl aicohoi” is preferred. Dukes at 7, it. 19-23.
`
`Dukes aiso disoiosos two different formulations of fuivostrant in its working oxampies.
`
`Example 1 from Dukes discloses fulvostrant “in a mixture of propylene glycol: ethanol:
`
`water: poloxamer 40?." Dukes at 8, ii. 35-37‘. Example 2 discloses a formuiarion
`
`“oontain{ing] 50 mg of ifuivesirantj, 400 mg of benzyi alcohol and sufficient caster oii to
`
`-13-
`
`Astrazeneca EX. 2142 p. 13
`
`
`
`Applioalion No.: 121285.887‘
`Attorney Docket No; 112850055-£30000
`
`bring the solution to a volume of ‘i ml” (“Dukes Castor oil formulation”). Dukes at 9,
`
`ll. 21-23.
`
`No explanation for why one of ordinary skill in the all would have moclllierl the
`
`Dukes oaetor oil formulation in any way is set forth in the Office Action. The Office
`
`seems to imply that one of ordinary skill in the art would have added ethanol and benzyl
`
`benzoete to Dukes oaetor oil formulation simply because ethanol and oenzyl lzenzoate
`
`were “known to be useful as commonly used solvents.” Office Action at 3. The focus in
`
`an obviousneee rejection, however, is not on what one of ordinary skill in the art could
`
`have clone, but rather “on what a person of ordinary el-till lo the pertinent art would have
`
`known at the time of the invention, and on what such a person would have reasonably
`
`expected to have been able to do in View of that knowledge.” ll/l.P.E.P. § 2141 .ll
`
`(emphasis added).
`
`in this regard, one of ordinary skill in the art attempting to improve any of the
`
`Dukes iorrnulations would have determined the solubility of fulvestranl in any test
`
`solvent before adding the solvent to the forrnolation. See, for example, Table 2 of the
`
`instant application, which reports solubility of fulveslrant in master oil, benzyl alcohol,
`
`ethanol, and loenzyl benzoete. According to Table 2, the solubility of fulveetrant in
`
`benzyl benzoele is 6.15 mgml“, whereas the corresponding solubility in benzyl alcohol
`
`is >200 mgml“. Thus, based on solubility clata, one of ordinary skill in the art would
`
`have realized that fulveetrenl is more than one orcleror magnitude more soluble in
`
`benzyl alcohol than in loenzyl loenzoate. Therefore, incorporating oenzyl benzoete into
`
`Dukes caster oil formulation at the expense of reducing the concentration of benzyl
`
`alcohol, as would be required to arrive at the formulation recited in the instant claims
`
`..‘j4..
`
`Astrazeneca EX. 2142 p. 14
`
`
`
`Application No.: 12/285,887
`Attorney Docket No: 1 128S.ClD5i6-00000
`
`starting from Dukes disclosure, would have been expected to decrease the solubility of
`
`fulvestrant in the resulting formulation. None of the references cited by the Office
`
`suggests otherwise. As mentioned before, decreasing the solubility of fulvestrant in a
`
`given fonnulation would exacerbate the problem of finding a suitable fonnulation for
`
`fulvestrant.
`
`Thus, none of the cited references would have suggested to one of ordinary skill
`
`in the art the modification of any of Dukes formulations by the addition of benzyl
`
`benzoate. For at least this reason, the Office has not made a prima facie case of
`
`obviousness and Applicants respectfully request that this rejection be withdrawn.
`
`I|.B
`
`The Office has not made the necessary factual findings to support a
`conclusion of obviousness
`
`By arguing that one of ordinary skill in the art would have added ethanoi and
`
`benzyl benzoate to Dukes castor oil formulation simply because the additional solvents
`
`were known in the an (Office Action at 3), the Office seems to be basing the rejection in
`
`a “combination of prior art elements” rationale. See, e.g., M.P.E.P. § 2143.A. However,
`
`an obviousness rejection under this rationale requires, among other requisites: (1) “a
`
`finding that .
`
`.
`
`. each element [in the combination] merely performs the same function as
`
`it does separately” and (2) “a finding that one of ordinary skill in the art would have
`
`recognized that the results of the combination were predictable.” Id. The Office has not
`
`met either of these requirements.
`
`First, the Office has not shown that the solvents proposed to be added to Dukes
`
`castor oil formulation, ethanol and benzyl benzoate, would have performed the same
`
`function in the resulting formulation as they performed separately, As explained in the
`
`-15-
`
`AstraZeneca Ex. 2142 p. 15
`
`
`
`Application No.: 12/285,887
`Attorney Docket No.: 112850056-00000
`
`previous section, the addition of benzyl benzoate to a given fulvestrant formulation
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`would have been expected to reduce the solubility of fulvestrant in the original
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`formulation. Table 3 in the instant specification compares the solubility of fulvestrant in
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`various formulations comprising ethanol, benzyl alcohol, and castor oil in the presence
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`and absence of benzyl benzoate.
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`In each case, the solubility of fulvestrant in the
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`solution containing benzyl benzoate increased compared to the solubility of fulvestrant
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`in the corresponding formulation without benzyl benzoate.
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`Id. The trend shown in
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`Table 3 demonstrates that benzyl benzoate is not “perforrn[ing] the same function as it
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`does separately.”
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`Second, because the addition of benzyl benzoate does not decrease the
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`solubility of fulvestrant in the resulting formulation, as would have been expected, the
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`Office cannot find that “one of ordinary skill in the art would have recognized that the
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`results of the combination were predictable.”
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`Even under an “obvious to try” rationale, the Office needs to show that "one of
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`ordinary skill in the art could have pursued the known potential solutions with a
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`reasonable expectation of success.” M.P.E.P. § 2143.E.
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`in the instant case, as shown
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`in Section ||.A above, one of ordinary skill in the art could not have expected that adding
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`benzyl benzoate to Dukes castor oil formulation, while decreasing the amount of benzyl
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`alcohol as would be required to arrive at the formulation recited in the instant claims,
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`would have resulted in a suitable fulvestrant formulation.
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`For the foregoing reasons, the Office has not met its burden of proving a prima
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`facfe case of obviousness. Accordingly, Applicants respectfully request that this
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`rejection be withdrawn.
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`-16-
`
`AstraZeneca Ex. 2142 p. 16
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`
`
`Application No.: 12/285,887
`Attorney Docket No.: 112850056-00000
`
`III. Double Patenting Rejection
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`The Office rejected claims 21-22 under the nonstatutory obviousness-type
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`double patenting doctrine as being unpatentable over: (a) claims 1-9 of US. Patent
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`No. 6,774,122 and (b) claims 1-12 of U.S. Patent No. 7,456,160.
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`Because Applicants cancelled claims 21 and 22 in this Response, this rejection is
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`now moot. Accordingly, Applicants respectfully request that this rejection be withdrawn.
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`IV. Conclusion
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`In view of the foregoing amendments and remarks, Applicants respectfully
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`request reconsideration of this application and the timely allowance of the pending
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`claims.
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`Please grant any extensions of time required to enter this response and charge
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`any required fees not included with this Hesponse to Deposit Account No. 06-0916.
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`Dated: June 20, 2011
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`Respectfully submitted,
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`FINNEGAN, HENDERSON, FARABOW,
`GARRETT & DUNNER, L.L.P.
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`/
`
`By: W V/\
`
`Carlos M. Téllez
`
`Fteg. No. 48,638
`(202) 408-4123
`
`-17-
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`AstraZeneca Ex. 2142 p. 17