OK TO ENTER: IJDA!
`
`01 /02/2014
`
`Electronic Filing
`
`IN THE UN ITED STATES PATENT AND TRADEMARK OFFICE
`
`Application of: Jerome B. Zeldis
`
`Group Art Unit: 1629
`
`Application No.: 12/621,502
`
`Confirmation No.: 2588
`
`Filed: November 19, 2009
`
`Exam iner: Anderson, James D.
`
`For: METHODS USING 3-( 4-A,VI1NO-J-OXO-J ,3-
`DlHYDRO-ISOINDOL-2 -YL)-PJPERIOIN E-2 ,6-
`DIONE FOR TREA H.·IENT OF MANTLE CELL
`LYMPHOMAS
`
`Attorney Docket No.: 9516-904-999
`(CAM: 501872-999904)
`
`RESPONSE UNDER 37 CFR § 1.116
`
`Commissioner for Patents
`P.O. Box 1450
`Alexandria, VA 22313-1 450
`
`Sir:
`
`In response to the final Office Action mailed September 19,2013, Applicant submits the
`
`following amendments and remarks for consideration by the Examiner and entry into the record
`
`of the above-captioned application. Applicant also submits herewith (i) a Certification and
`
`Request for Consideration Under The After Final Cons ideration Pilot Program 2.0; (ii) a
`
`Declaration under 37 C.F.R. § 1.132 with Exhibits A and B; and (iii) and a supplemental
`
`Information Disclosure Statement.
`
`Amendment to the Claims are shown in a listing of the claims that begins on page 2 of
`
`this paper.
`
`Remarks begin on page 6 of th is paper.
`
`Apotex Ex. 1007, p. 1
`
`

`

`Electronic Filing
`
`IN TH E UN ITE D ST ATES PATENT AN D T RADEMA RK OF FICE
`
`Application of: Jerome B. Zeldis
`
`Group Art Unit: 1629
`
`Application No.: 12/621,502
`
`Confirmation No.: 2588
`
`Filed: November 19, 2009
`
`Exam iner: Anderson, James D.
`
`For: METHODS USING 3-( 4-A,vIINO-J-oxO-1 ,3 -
`DlHYDRO-ISOINDOL-2-Y L)-PJPERIOI NE-2 ,6-
`DIONE FOR TREA H.·IENT OF MANTLE CELL
`LYMPHOMAS
`
`Attorney Docket No.: 9516-904-999
`(CAM: 501872-999904)
`
`RES PONSE UN DER 37 C FR § 1.11 6
`
`Commissioner for Patents
`P.O. Box 1450
`Alexandria, VA 223\3-1450
`
`Sir:
`
`In response to the final Office Action mailed September \9,20 13, Applicant submits the
`
`followi ng amendments and remarks fo r consideration by the Examiner and entry into the record
`
`of the above-captioned application. Appl icant also subm its herewith (i) a Certi fication and
`
`Request for Consideration Under The After Fi nal Consideration Pilot Program 2.0; (ii) a
`
`Declaration under 37 C.F.R. § 1.132 with Exhibits A and B; and (iii) and a supplemental
`
`In formation Disclosure Statement.
`
`Amendment to the Claims are shown in a listing of the claims that begins on page 2 of
`
`this paper.
`
`Rem arks begin on page 6 of th is paper.
`
`Apotex Ex. 1007, p. 2
`
`

`

`U.S. Pat. Appln. No. 121621 ,502
`Attorney Docket No. 9516-904-999
`Response to Office Action dated Sep. 19, 2013
`Filed on Dec . 18,2013
`
`AMEN DM ENTS TO T HE CLAIMS
`
`This listing of claims will replace all prior versions, and listings, of claims in the application.
`
`Listing of Clai ms:
`
`I.
`
`(Currently Amended) A method of treating mantle cell lymphoma in a human,
`
`which comprises (a) administering to a human having mantle cell lymphoma from about 5 mg to
`
`about 25 mg per day of 3-( 4-amino-l-oxo-I,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione or a
`
`pharmaceutically acceptable salt or hydrate thereof for a J'.leriod of time 21 davs followed by a
`
`period of seven days rest in a 28 day cycle; and (b) repeating step (a), wherein the mant le cell
`
`lymphoma is relapsed. refractory, or relapsed and refractory to conventional therapy.
`
`2.
`
`3.
`
`(Canceled)
`
`(Currently Amended) The method of claim 1;>', wherein the amount of 3-(4-
`
`am ino-oxo- I,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione administered is about 5, 10, IS, 20 or
`
`25 mg per day.
`
`4.
`
`(Previously Presented). The method of claim 3, wherein the amount of 3-(4-
`
`amino-oxo-I,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione administered is about 10, 15, 20, or
`
`25 mg per day.
`
`5.
`
`(Previously Presented). The method of claim 4, wherein the amount of3-(4-
`
`amino-oxo-I,3-dihydro-isoindo l-2-yl)-piperidine-2,6-dione adm inistered is about 25 mg per day.
`
`6.
`
`(Previously Presented) The method of claim 3_ wherein 3-(4-amino-oxo-1 ,3-
`
`dihydro-i soi ndol-2-yl)-piperidine-2.6-dio ne adm ini stered is enantiomeri cally pure.
`
`7.
`
`(Prev iously Presented) The method of claim 6, wherein 3-(4-amino-oxo-1 ,3-
`
`dihydro-isoindol -2-yl)-piperidine-2,6-dione administered is S enantiomer.
`
`2
`
`Apotex Ex. 1007, p. 3
`
`

`

`U.S. Pat. Appln. No. 12/621,502
`Attorney Docket No. 9516-904-999
`Response to Office Action dated Sep. 19, 2013
`Filed on Dec. 18, 2013
`
`8.
`
`(Previously Presented) The method of claim 6, where in 3-(4-amino-oxo-1 ,3-
`
`dihydro-isoindol-2-yl)-piperidine-2,6-dione administered is R enantiomer.
`
`9.
`
`(Previously Presented) The method of claim 3, wherein 3-(4-amino-oxo-I,3-
`
`dihydro-isoindol-2-yl)-piperidine-2,6-dione is a~ministered orally.
`
`10.
`
`(Previously Presented) The method of claim 9, where in 3-( 4-amino-oxo-I,3-
`
`dihyd ro-isoindol-2-yl)-piperidine-2,6-dione is administered in the foml of a capsule or tablet.
`
`II.
`
`(Canceled)
`
`12.
`
`(Canceled)
`
`(Current ly Amended) The method of claim 1 R, further comprising
`13.
`administration ofrituximab in an amount of375 mg/m2 by intravenous infusion weekly.
`
`14.
`
`(Currently Amended) A method of treating mantle cell lymphoma, which
`
`comprises (a) administering to a patient having mantle cell lymphoma from about 5 mg to about
`
`25 mg per day of 3-(4-amino-oxo-I,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione or a
`
`phannaceutically acceptable salt or hydrate thereof for a period of time 21 days followed by a
`
`period of seven days rest in a 28 day cycle; (b) repeating step (a); (c) administering to the patient
`
`a therapeutically effective amount ora second active agent selected from a hematopoietic growth
`
`factor, a cytokine, an anticancer agent, an antibiotic, a cox-2 inhibitor, a corticosteroid, rituximab,
`
`or a combination thereof for a period of time fo llowed by a period of rest; and (d) repeating step
`
`(c). wherein the mantle cell lymphoma is relapsed. refractorv, or relapsed and refractory to
`
`conventional therapy.
`
`15 .
`
`(PrevioLisly Presented) The method of claim 14, wherein the second active agent
`
`is rituximab.
`
`16.
`
`(Previously Presented) The method of claim 14, wherein the second active agent
`
`is dexamethasone.
`
`3
`
`Apotex Ex. 1007, p. 4
`
`

`

`u.s. Pat. Appln. No. 12/621.502
`Attorney Dockel No. 9516-904-999
`Response 10 Office Action dated Sep. 19,2013
`Filed on Dec. 18,2013
`
`17.
`
`(Previously Presented) The method of claim 14, wherein the second active agent
`
`is prednisone.
`
`18.
`
`(Currently Amended) The method of claim 1 or 14, wherein the amount of3-(4-
`
`amino-oxo-I ,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione administered is about 5 mg to about
`
`25 mg per day for 21 days followed by seven days rest in a 28 day cye le.
`
`19.
`
`(Currently Amended) The method of claim 18, wherein the amount of3-(4-
`
`amino-oxo- I,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione administered is about 5 mg per day
`
`for 21 days fallowed by seven days rest in 8 28 day cycle.
`
`20.
`
`(Currently Amended) The method of claim 18, wherein the amount of 3-(4-
`
`amino-oxo-I,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione administered is about 10 mg per day
`
`for 21 days followed by seven days rest in a 28 day e~'cle.
`
`21.
`
`(Currently Amended) The method of claim 18, wherein the amount of 3-(4-
`
`amino-oxo-l ,3 -dihydro-isoindol-2-y l)-piperidine-2 ,6-dione administered is about 15 mg per day
`
`for 21 days followed by seven days rest in a 28 day cyc le.
`
`22.
`
`(Currently Amended) The method of claim 18, wherein the amount of 3-(4 -
`
`amino-oxo-I ,3-dihydro-isoindo l-2-yl)-piperidine-2,6-dione administered is about 20 mg pe r day
`
`for 21 days followed by seven days rest in 8 28 day cycle.
`
`23.
`
`(Currently Amended) The method of claim 18, wherein the amount of 3-(4-
`
`amino-oxo-l,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione admin istered is about 25 mg per day
`
`for 21 days follo ..... ed by seVCB days rest ill a 28 day eycle.
`
`24.
`
`(Previously Presented) The method of claim 14, wherein 3-(4-amino-oxo-1.3-
`
`dihydro-isoindol-2-yl)-piperidine-2.6-dione is administered orall y.
`
`25.
`
`(Previous ly Presented) The method of claim 24, wherein 3-(4-amino-oxo-l,3-
`
`dihydro-isoindol-2-yl)-piperidine-2,6-dione is administered in the form of a capsule or tablet.
`
`4
`
`Apotex Ex. 1007, p. 5
`
`

`

`U.S. Pat. Appln . No. 12/621 ,502
`Attorney Docket No. 9516·904·999
`Response 10 Office Action dated Sep. 19,2013
`Filed on Dcc. 18, 20 13
`
`(Previously Presented) The method of claim 15. wherein {he rituximab is
`26.
`administered in an amount of 375 mg/m2 by intravenous infusion weekly.
`
`27.
`
`(Previously Presented) The method of claim 14, wherein the anticancer agent is a
`
`proteasome inhibitor.
`
`5
`
`Apotex Ex. 1007, p. 6
`
`

`

`U.S. Pal. Appln . No. 12/621 ,502
`Attorney Docket No. 9516-904-999
`Response to Office Action dated Sep. 19.2013
`Filed on Dec. 18. 20 13
`
`I.
`
`Applicant's Statement of the Substan ce of Inte rv iew
`
`REM A RKS
`
`Applicant thank s Examiner James D. Anderson for the courtesy extended during the
`
`interview on October 9, 2013 with Dr. Donna Robertson-Chow (Ce lgene Corporation, Ass ignee
`
`of the present application), Lei Zhang, M.D. (Celgene Corporat ion), Yeah-Sil Moon (allomey for
`
`Applicant), and Wei Zhang (attorney for Appl icant).
`
`Amendments to the claims and patentability of the claims were discussed during the
`
`interview. Without acqu iescing to the propriety of the rejections and solely to expedite
`
`allowance o f the application, Applicant proposed to amend independent claims 1 and 14 to rec ite
`
`that: ( I) the mantle cel l lymphoma is relapsed, refractory, or relapsed and refractory; and (2) the
`
`compound 3-( 4-amino-I-oxo-I,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione (i. e. , lenalidomide)
`
`or a phannaceutical ly acceptab le salt or hydrate thereof is administered for 21 days followed by
`
`seven days rest in a 28 day cycle. Applicant submitted that one sk illed in the art would not have
`
`concluded that the compound thalidomide was therapeuticall y elTective in treating mantle cell
`
`lymphoma from the di sclosure of the cited references. In addition, at the time the present
`
`application was filed, the re was an unmet need in therapeutic options for mantle cell lymphoma
`
`patients, in particular those with relapsed, refractory, or re lapsed and refractory mantle cell
`
`lymphoma. Moreover, the therapeutic effect of lena lid om ide in relapsed, refractory, or relapsed
`
`and refrac tory mantle cell myeloma, as demonstrated in a Phase II cl inical study, would have
`
`been unexpected at the time of fili ng this application.
`
`The Examiner agreed that the amended claims would likely to be all owable. Applicant
`
`submits herewith a declaration by Le i Zhang. M.D., under 37 C. F.R. § 1.132, as requested by the
`
`Examiner.
`
`II.
`
`C hlim Amendm ents
`
`Prior to entry of this paper, claims 1-27 were pending in this appl ication. Claims 2, I I
`
`and 12 have been canceled without prejudice. App licant reserve the right to pursue the subject
`
`matter of the canceled claims in one or more re lated applications. Claims I and 14 have been
`
`6
`
`Apotex Ex. 1007, p. 7
`
`

`

`U.S, Pat. Appln. No. 12/621,502
`Attorney Docket No. 9516-904-999
`Response to Office Action dated Sep. 19,2013
`Filed on Dec. 18,2013
`
`amended as indicated above. (n addition, claims 3, 13 and 18-23 have been amended in view of
`
`the amendments to claims 1 and 14 and claim cancell ation. No new matter has been added.
`
`III.
`
`The Rejection Under 35 U.S.c. § 103(a) Should Be Withdrawn
`
`Claims \-26 remain rejected under 35 U.S.c. § I 03(a) as allegedly being unpatentable
`
`over Zeldis (U.S. Publication No. 200410029832 A I; "Zeldis'") in view of Damaj et al.
`
`(Leukemia , 2003, vol. 17, pages 1914-1915; " Damar), Wi lson et al. (British J of Haemaf%gy,
`
`2002, vol. 119, pages 128-130; "Wilson"), and Kaufmann el 01. (Blood, 2004, vol. 104, no. 8,
`
`pages 2269-2271; "Kaufmann"). (Office Action at 10.) Claim 27 remains rejected under
`
`35 U.S.c. § 103(a) as allegedly being unpatentable over Zeldis in view of Damaj, Wilson, and
`
`Kaufmann as applied to claims 1-26 above, and further in view of Witzig (.1. Clin. Oncol., 2005,
`
`vol. 23, no. 26, pages 6409-6414). (Id. at 19.). The Examiner acknowledges that Zeldis does not
`
`explicitly disclose treating mantle ce ll lymphoma with lenalidomide, but contends that it teaches
`
`that lenalidomide is more potent than thalidomide in certain biological activities. (See, e.g.,
`
`Office Action at 5, 13-15.) The Examiner then alleges that the secondary references, Damaj,
`
`Wilson and Kaufmann, teach that thalidomide is effective in mantle cell lymphoma, and
`
`therefore would have motivated a person skilled in the art to substitute lenalidomide for
`
`thalidomide to treat mantle cell lymphoma. (See, e.g., id. at 6,-7,18.)
`
`For the reasons stated in the response filed on December 4, 2012, App li cant disagrees
`
`with the these rejections. Nevertheless, solely to expedite prosecution of the present application,
`
`Applicant has amended claims I and 14 to define that the mantle cell lymphoma treated with
`
`lenalidomide is relapsed , refractory, or re lapsed and refractory, and that lenalidomide is
`
`administered for 21 days foll owed by seven days rest in a 28 day cycle. As Applicant explained
`
`in the 1.132 declaration, one skilled in the art would not have concluded based on the di sclosure
`
`ofDamaj, Wilson and Kaufmann that the compound thalidomide would be therapeuticall y
`
`effective in treating mantle cell lymphoma. In addition, the efficacy of lena lid om ide in relapsed,
`
`refractory, or relapsed and refractory mantle cell lymphoma, as demonstrated by the response
`
`rates, median duration of response and median overall survival in a Phase II clinical study, would
`
`7
`
`Apotex Ex. 1007, p. 8
`
`

`

`u.s. Pat. Appln. No. 12/621,502
`Attorney Docket No. 9516· 904·999
`Response to Office Action dated Sep. 19,2013
`FiledonDec.18,2013
`
`have been unexpected and surprising at the time the claimed invention was made. See a/so the
`
`1.132 declaration enclosed herewith.
`
`Therefore, claims 1-26 are believed to be patentable over Zeldis in view of Damaj ,
`
`Wilson and Kaufmann, and the rejection unde r 35 U.S.c. § 103(a) should be withdrawn.
`
`Witzig is cited for the disclosure that among others, proteasome inhibitors represent a
`
`new treatment option for mantle cell lymphoma patient. It does not cure the deficiency of Zeldis
`
`in view of Damaj, Wilson and Kaufmann discussed above. Therefore, the rejection of claim 27
`
`under 35 U.S.C. § 103(a) should also be withd rawn.
`
`IV.
`
`The Double Patenting Rejection Should Be Withdrawn
`
`A. The claims are patentable over the clai ms of the ' 230 patent in view of Zeldis,
`Damaj, Wilson and Kaufmann
`
`Claims 1-1 6 and 18-26 are rejected on the ground of nonstatutory obviousness-type
`double patenting as all eged ly being unpatentable over claims 18-26 of U.s. Patent No. 6,281,230
`(the "'230 patent") in view of Zeldis, Damaj, Wilson, and Kaufmann. (Office Action at 23.)
`
`The Exam iner acknowledges that the claims of the '230 patent broadl y recite a method of
`
`treating an oncogenic or cancerous disease by adm inistering lenalidomide, but they do not recite
`
`the treatment of mantle cell lymphoma with the specifi c dosing regimen of lena lid om ide.
`
`Nevertheless, the Examiner contends that the teachings of Zeldis, Damaj, Wilson, and Kaufmann
`
`would teach, suggest and motivate one skilled in the art to adm inister lenalidomide to treat
`
`mantle ce ll lymphoma, for the reasons provided in the obviousness rejections. (Id.) Applicant
`
`respectfull y disagrees with this rejection.
`
`As acknowledged by the Examiner, none of the asserted cla ims of the ·230 patent recites
`
`the treatment of re lapsed, refractory, or relapsed and refractory mantie cell lymphoma, or the
`
`dosing regimen in the presen t claims. In addition, as discussed above in connection with the
`
`obviousness rej ec tion, Zeldis, Damaj, Wilson, and Kaufmann do not disclose or suggest methods
`
`of treating relapsed, refractory, or relapsed and refractory mantle cell lymphoma with the
`
`specific dosing regimen of lenal idomide as recited in the claims. Therefore, these secondary
`
`references do not cure the deficiencies of claims J 8-26 of the '230 patent. Lastly, the unexpected
`
`8
`
`Apotex Ex. 1007, p. 9
`
`

`

`U.S. Pat. Appln. No. 121621,502
`Attorney Docket No. 9516·904·999
`Response to Office Action dated Scpo 19, 2013
`Filed on Dec. 18, 2013
`
`results of lenalidomide in the treatment of relapsed, refractory, or relapsed and refractory mantle
`
`cell lymphoma presented by Appl icant in the 1.132 declaration would rebut any presumption of
`
`obviousness that may have been established by the cited references.
`
`In view of the foregoing, Appl icant respectfully submits that the present claims are
`
`patentable over claims 18·26 of the ' 230 patent in view of Zeldis, Damaj, Wilson and
`
`Kaufmann.
`
`B. The claims are patentable over the claims of the '363 patent in view of Damaj
`
`Claims 1-1 5 and 18-26 are rejected on the ground of nonstatutory obviousness-type
`
`doub le patenting as allegedly being unpatentable over claims 1,7, 9-15 and 17-24 of U.S. Patent
`
`No. 7,468,363 (the "'363 patent") in view ofDamaj. (Office Action at 24.) The Exami ner
`
`acknowledges that the asserted claims of the '363 patent broadly recite a method of treati ng non(cid:173)
`
`Hodgkin' s lymphoma and cutaneous or diffuse large B-celllymphoma by administering
`
`lenal idomide, but not the mantle cell lymphoma. (fd.) Nevertheless, the Examiner contends that
`
`mantle cell lymphoma is an aggressive B-ceillymphoma accordi ng to Damaj and also is a type
`
`or non-Hodgkin's lymphoma as described in the present application. (Jd.) Therefore, it would
`
`have been obvious to one skilled in the art to administer lenalidomide to treat mantle cell
`
`lymphoma. Applicant respectfully disagrees with thi s rejection.
`
`As acknowledged by the Examiner, none of the asserted claims of the ' 363 patent recites
`
`the treatment of reJapsed, refractory, or re lapsed and refractory mantl e ceJllymphoma. Nor is
`
`mant le cell lymphoma disclosed in the specification of the ' 363 patent. Thus, one skilled in the
`
`art, upon reviewing the claims of the ' 363 patent, wou ld not have had a reason to particularly
`
`modify these claims to administer lenali domide to treat relapsed, refractory, or relapsed and
`
`refractory mantle cell lymphoma. Damaj is directed to the use of thalidomide, not lenalidomide
`
`claimed in the ' 363 patent. [n addition, as di scussed earl ier in connection with the obviousness
`
`rejection, Damaj would not have led one skilled in the art to conclude that thalidomide is
`
`therapeutically effective in treating mante l ce tl lymphoma, let alone motivating the skilled
`
`person to use another compound to treat relapsed, refractory, or re lapsed and refractory mant le
`
`cell lymphoma. Therefore. Damaj does not cure the deficiency of the asserted clai ms of the '363
`
`9
`
`Apotex Ex. 1007, p. 10
`
`

`

`U.S. Pal. Appln. No. 12/621,502
`Attorney Docket No. 95 16·904·999
`Response to Office Action dated Sep. 19,20[3
`Filed on Dec. [8,2013
`
`patent. Lastly, the unexpected results of lenalidomide in the treatment of relapsed, refractory, or
`
`relapsed and refractory mantle cell lymphoma presented by Applicant in the 1. 132 declaration
`
`would rebut any presumption of obviousness that may have been established by the cited
`
`references.
`
`Therefore, the present claims are patentable over claims 1,7,9- 15 and 17-24 of the '363
`
`patent in view of Damaj. App licant respectfully requests that the rejections under the
`
`obviousness-type double patenting be withdrawn.
`
`CONCLUSION
`
`Appl icant respectfully submits that the present app lication is in condition for allowance.
`
`A favo rable disposition to that effect is respectfully requested. Should the Examiner not agree
`
`that all claims are allowable, a further personal or telephonic interview is respectfully requested
`
`to discuss any remaini ng issues and to accelerate allowance of the above-captioned appl ication.
`
`Please charge any required fees to Jones Day Deposit Account No. 50-3013.
`
`Date: December 18, 2013
`
`Respectfully submi tted,
`
`Wyl t<v~
`bq,rr,> /
`7Y~e-ah~.~S~il~M~oo-I-' --------~(R~e-g-.7N~o-.~52~,~0742~)
`Jones Day
`222 East 41 st Street
`New York, NY 10017·6702
`Tel: 212·326·3939
`Fax: 212·755·7306
`
`10
`
`Apotex Ex. 1007, p. 11
`
`