PATENT
`
`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`Applicants:
`
`Myers et al.
`
`Examiner:
`
`Janet L. Epps-Smith
`
`Serial No.:
`
`13/964,975
`
`Group Art Unit:
`
`1633
`
`Confirmation No.:
`
`8904
`
`Docket:
`
`2333-2 CON 11
`
`Filed:
`
`For:
`
`August 12, 2013
`
`Dated:
`
`January 2, 2014
`
`SUBLINGUAL AND
`BUCCAL FILM
`COMPOSITIONS
`
`Mall Stop Amendment
`Commissioner for Patents
`P.O. Box 1450
`Alexandria, Virginia 22313—1450
`
`Certificate of EFS-Web Transmission
`
`I hereby certify that this correspondence is being transmitted
`to the U.S. Patent and Trademark Office Via the Office’s
`electronic filing system.
`.
`Dated W
`
`Signature:
`/Stephen J. Brown/ Stephen Brown
`
`AMENDMENT AND RESPONSE TO OFFICE ACTION
`
`Madam:
`
`In response to the Office Action dated November 7, 2013, a response to which is due
`
`by February 7, 2014, the Applicants offer the following amendments and remarks.
`
`Amendments to the Claims begin on page 2 of this submission.
`
`Remarks/Arguments begin on page 9 of this submission.
`
`BDSI vs. RB Pharmaceuticals Limited
`
`Page 1
`
`|PR2014-00325
`
`BDSI Exhibit 1038
`
`Page 1
`
`

`

`Applicants: Myers et al.
`Serial No.: 13/964,975
`
`Filing Date: August 12, 2013
`Docket No.: 2333-2 CON II
`
`Page 2
`
`Amendments to the Claims:
`
`This listing of claims shall replace all previous listings of claims:
`
`1. (Currently Amended) An orally dissolving film formulation comprising from about 2 to
`
`about 16 mg of buprenorphine and from about 0.5 to about 4 mg of naloxone, wherein said
`
`formulation provides an in vivo plasma profile having a mean Cmax of between about 0.6
`
`ng/ml and about 5.7 ng/ml for buprenorphine and an in vivo plasma profile having a mean
`
`Cmax of between about 41 pg/ml to about 324 pg/ml for naloxone; wherein said film
`
`formulation further comprises one or more polymers and the ratio of a free base eguivalent
`
`amount of said buprenomhine to the total amount of said one or more polymers is from about
`
`1:0.6 to about 1:25 by weight.
`
`2. (Original) The film formulation of claim 1, comprising about 2 mg of buprenorphine and
`
`about 0.5 mg of naloxone, wherein said formulation provides an in vivo plasma profile
`
`having a mean Cmax of between about 0.6 ng/ml and about 1.0 ng/ml for buprenorphine and
`
`an in vivo plasma profile having a mean Cmax of between about 41 pg/ml to about 65 pg/ml
`
`for naloxone.
`
`3. (Original) The film formulation of claim 1, comprising about 4 mg of buprenorphine and
`
`about 1 mg of naloxone, wherein said formulation provides an in vivo plasma profile having
`
`a mean Cmax of between about 1.0 ng/ml and about 1.7 ng/ml for buprenorphine and an in
`
`vivo plasma profile having a mean Cmax of between about 64 pg/ml to about 102 pg/ml for
`
`naloxone.
`
`4. (Original) The film formulation of claim 1, comprising about 8 mg of buprenorphine and
`
`about 2 mg of naloxone, wherein said formulation provides an in vivo plasma profile having
`
`a mean Cmax of between about 1.8 ng/ml and about 2.9 ng/ml for buprenorphine and an in
`
`vivo plasma profile having a mean Cmax of between about 75 pg/ml to about 119 pg/ml for
`
`naloxone.
`
`Page 2
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`Page 2
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`

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`Applicants: Myers et al.
`Serial No.: 13/964,975
`
`Filing Date: August 12, 2013
`Docket No.: 2333-2 CON II
`
`Page 3
`
`5. (Original) The film formulation of claim 1, comprising about 12 mg of buprenorphine and
`
`about 3 mg of naloxone, wherein said formulation provides an in vivo plasma profile having
`
`a mean Cmax of between about 2.5 ng/ml and about 4.1 ng/ml for buprenorphine and an in
`
`vivo plasma profile having a mean Cmax of between about 159 pg/ml to about 250 pg/ml for
`
`naloxone.
`
`6. (Original) The film formulation of claim 1, comprising about 16 mg of buprenorphine and
`
`about 4 mg of naloxone, wherein said formulation provides an in vivo plasma profile having
`
`a mean Cmax of between about 3.6 ng/ml and about 5.7 ng/ml for buprenorphine and an in
`
`vivo plasma profile having a mean Cmax of between about 207 pg/ml to about 324 pg/ml for
`
`naloxone.
`
`7. (Currently Amended) An orally dissolving film formulation comprising from about 2 to
`
`about 16 mg of buprenorphine and from about 0.5 to about 4 mg of naloxone, wherein said
`
`formulation provides an in vivo plasma profile having a mean Cmax of between about 0.7
`
`ng/ml and about 6.9 ng/ml for buprenorphine and an in vivo plasma profile having a mean
`
`Cmx of between about 40 pg/ml to about 405 pg/ml for naloxone; wherein said film
`
`formulation further comprises one or more polymers and the ratio of a free base eguivalent
`
`amount of said buprenorphine to the total amount of said one or more polymers is from about
`
`1:0.6 to about 1:25 by weight.
`
`8. (Original) The film formulation of claim 7, comprising about 2 mg of buprenorphine and
`
`about 0.5 mg of naloxone, wherein said formulation provides an in vivo plasma profile
`
`having a mean Cmax of between about 0.7 ng/ml and about 1.2 ng/ml for buprenorphine and
`
`an in vivo plasma profile having a mean Cmax of between about 40 pg/ml to about 64 pg/ml
`
`for naloxone.
`
`9. (Original) The film formulation of claim 7, comprising about 4 mg of buprenorphine and
`
`about 1 mg of naloxone, wherein said formulation provides an in vivo plasma profile having
`
`a mean Cmax of between about 1.2 ng/ml and about 2.0 ng/ml for buprenorphine and an in
`
`Page 3
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`Page 3
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`

`

`Applicants: Myers et al.
`Serial No.: 13/964,975
`
`Filing Date: August 12, 2013
`Docket No.: 2333-2 CON II
`
`Page 4
`
`vivo plasma profile having a mean Cmax of between about 72 pg/ml to about 113 pg/ml for
`
`naloxone.
`
`10. (Original) The film formulation of claim 7, comprising about 8 mg of buprenorphine and
`
`about 2 mg of naloxone, wherein said formulation provides an in vivo plasma profile having
`
`a mean Cmax of between about 2.1 ng/ml and about 3.4 ng/ml for buprenorphine and an in
`
`vivo plasma profile having a mean Cmax of between about 104 pg/ml to about 163 pg/ml for
`
`naloxone.
`
`11. (Original) The film formulation of claim 7, comprising about 12 mg of buprenorphine and
`
`about 3 mg of naloxone, wherein said formulation provides an in vivo plasma profile having
`
`a mean Cmax of between about 3.3 ng/ml and about 5.3 ng/ml for buprenorphine and an in
`
`vivo plasma profile having a mean Cmax of between about 196 pg/ml to about 308 pg/ml for
`
`naloxone.
`
`12. (Original) The film formulation of claim 7, comprising about 16 mg of buprenorphine and
`
`about 4 mg of naloxone, wherein said formulation provides an in vivo plasma profile having
`
`a mean Cmax of between about 4.3 ng/ml and about 6.9 ng/ml for buprenorphine and an in
`
`vivo plasma profile having a mean Cmax of between about 259 pg/ml to about 405 pg/ml for
`
`naloxone.
`
`13. (Currently Amended) An orally dissolving film formulation comprising buprenorphine
`
`and naloxone that is bioequivalent to a SUBOXONE® tablet containing from about 2 to about
`
`16 mg of buprenorphine and from about 0.5 to about 4 mg of naloxone such that said
`
`formulation provides an in vivo plasma profile having a mean Cmax of between about 0.6
`
`ng/ml and about 5.7 ng/ml for buprenorphine and an in vivo plasma profile having a mean
`
`Cmax of between about 41 pg/ml to about 324 pg/ml for naloxone; wherein said film
`
`formulation further comprises one or more polymers and the ratio of a free base eguivalent
`
`amount of said buprenogghine to the total amount of said one or more polymers is from about
`
`1:06 to about 1:25 by weight.
`
`Page 4
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`Page 4
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`

`

`Applicants: Myers et al.
`Serial No.: 13/964,975
`
`Filing Date: August 12, 2013
`Docket No.: 2333-2 CON II
`
`Page 5
`
`14. (Original) The film formulation of claim 13 wherein said film formulation comprising
`
`buprenorphine and naloxone is bioequivalent to a SUB OXONE® tablet containing about 2
`
`mg of buprenorhphine and about 0.5 mg of naloxone such that said formulation provides an
`
`in vivo plasma profile having a mean Cmax of between about 0.6 ng/ml and about 1.0 ng/ml
`
`for buprenorphine and an in vivo plasma profile having a mean Cmax of between about 41
`
`pg/ml to about 65 pg/ml for naloxone.
`
`15. (Original) The film formulation of claim 13 wherein said film formulation comprising
`
`buprenorphine and naloxone is bioequivalent to a SUBOXONE® tablet containing about 4
`
`mg of buprenorhphine and about 1 mg of naloxone such that said formulation provides an in
`
`vivo plasma profile having a mean Cmax of between about 1.0 ng/ml and about 1.7 ng/ml for
`
`buprenorphine and an in vivo plasma profile having a mean Cmax of between about 64 pg/ml
`
`to about 102 pg/ml for naloxone.
`
`16. (Original) The film formulation of claim 13 wherein said film formulation comprising
`
`buprenorphine and naloxone is bioequivalent to a SUB OXONE® tablet containing about 8
`
`mg of buprenorhphine and about 2 mg of naloxone such that said formulation provides an in
`
`vivo plasma profile having a mean Cmax of between about 1.8 ng/ml and about 2.9 ng/ml for
`
`buprenorphine and an in vivo plasma profile having a mean Cmax of between about 75 pg/ml
`
`to about 119 pg/ml for naloxone.
`
`17. (Original) The film formulation of claim 13 wherein said film formulation comprising
`
`buprenorphine and naloxone is bioequivalent to a SUB OXONE® tablet containing about 12
`
`mg of buprenorhphine and about 3 mg of naloxone such that said formulation provides an in
`
`vivo plasma profile having a mean Cmax of between about 2.5 ng/ml and about 4.1 ng/ml for
`
`buprenorphine and an in vivo plasma profile having a mean Cmax of between about 159 pg/ml
`
`to about 250 pg/ml for naloxone.
`
`18. (Original) The film formulation of claim 13 wherein said film formulation comprising
`
`buprenorphine and naloxone is bioequivalent to a SUB OXONE® tablet containing about 16
`
`mg of buprenorhphine and about 4 mg of naloxone such that said formulation provides an in
`
`Page 5
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`Page 5
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`

`

`Applicants: Myers et al.
`Serial No.: 13/964,975
`
`Filing Date: August 12, 2013
`Docket No.: 2333-2 CON II
`
`Page 6
`
`vivo plasma profile having a mean Cmax of between about 3.6 ng/ml and about 5.7 ng/ml for
`
`buprenorphine and an in vivo plasma profile having a mean Cmax of between about 207 pg/ml
`
`to about 324 pg/ml for naloxone.
`
`19. (Currently Amended) An orally dissolving film formulation comprising buprenorphine
`
`and naloxone that is bioequivalent to a SUBOXONE® Film comprising from about 2 to about
`
`16 mg of buprenorphine and from about 0.5 to about 4 mg of naloxone such that said
`
`formulation provides an in vivo plasma profile having a mean Cmax of between about 0.7
`
`ng/ml and about 6.9 ng/ml for buprenorphine and an in vivo plasma profile having a mean
`
`Cmax of between about 40 pg/ml to about 405 pg/ml for naloxone; wherein said film
`
`formulation further comprises one or more polymers and the ratio of a free base eguivalent
`
`amount of said buprenomhine to the total amount of said one or more polymers is from about
`
`1:0.6 to about 1:25 by weight.
`
`20. (Original) The film formulation of claim 19 wherein said film formulation comprising
`
`buprenorphine and naloxone is bioequivalent to a SUB OXONE® Film comprising about 2 mg
`
`of buprenorphine and about 0.5 mg of naloxone such that said formulation provides an in
`
`vivo plasma profile having a mean Cmax of between about 0.6 ng/ml and about 1.0 ng/ml for
`
`buprenorphine and an in vivo plasma profile having a mean Cmax of between about 41 pg/ml
`
`to about 65 pg/ml for naloxone.
`
`21. (Original) The film formulation of claim 19 wherein said film formulation comprising
`
`buprenorphine and naloxone is bioequivalent to a SUB OXONE® Film comprising about 4 mg
`
`of buprenorphine and about 1 mg of naloxone such that said formulation provides an in vivo
`
`plasma profile having a mean Cmax of between about 1.2 ng/ml and about 2.0 ng/ml for
`
`buprenorphine and an in vivo plasma profile having a mean Cmax of between about 72 pg/ml
`
`to about 113 pg/ml for naloxone.
`
`22. (Original) The film formulation of claim 19 wherein said film formulation comprising
`
`buprenorphine and naloxone is bioequivalent to a SUB OXONE® Film comprising about 8 mg
`
`of buprenorphine and about 2 mg of naloxone such that said formulation provides an in vivo
`
`Page 6
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`Page 6
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`

`

`Applicants: Myers et al.
`Serial No.: 13/964,975
`
`Filing Date: August 12, 2013
`Docket No.: 2333-2 CON II
`
`Page 7
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`plasma profile having a mean Cmax of between about 2.1 ng/ml and about 3.4 ng/ml for
`
`buprenorphine and an in vivo plasma profile having a mean Cmax of between about 104 pg/ml
`
`to about 163 pg/ml for naloxone.
`
`23. (Original) The film formulation of claim 19 wherein said film formulation comprising
`
`buprenorphine and naloxone is bioequivalent to a SUB OXONE® Film comprising about 12
`
`mg of buprenorphine and about 3 mg of naloxone such that said formulation provides an in
`
`vivo plasma profile having a mean Cmax of between about 3.3 ng/ml and about 5.3 ng/ml for
`
`buprenorphine and an in vivo plasma profile having a mean Cmax of between about 196 pg/ml
`
`to about 308 pg/ml for naloxone.
`
`24. (Original) The film formulation of claim 19 wherein said film formulation comprising
`
`buprenorphine and naloxone is bioequivalent to a SUB OXONE® Film comprising about 16
`
`mg of buprenorphine and about 4 mg of naloxone such that said formulation provides an in
`
`vivo plasma profile having a mean Cmax of between about 4.3 ng/ml and about 6.9 ng/ml for
`
`buprenorphine and an in vivo plasma profile having a mean Cmax of between about 259 pg/ml
`
`to about 405.00 pg/ml for naloxone.
`
`25. (New) The film formulation of claim 1, wherein the ratio of a free base equivalent amount
`
`of said naloxone to the total amount of said one or more polymers is from about 1:2 to about
`
`1:100 by weight.
`
`26. (New) The film formulation of claim 7, wherein the ratio of a free base equivalent amount
`
`of said naloxone to the total amount of said one or more polymers is from about 1:2 to about
`
`1:100 by weight.
`
`27. (New) The film formulation of claim 13, wherein the ratio of a free base equivalent
`
`amount of said naloxone to the total amount of said one or more polymers is from about 1:2
`
`to about 1:100 by weight.
`
`Page 7
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`Page 7
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`

`

`Applicants: Myers et al.
`Serial No.: 13/964,975
`
`Filing Date: August 12, 2013
`Docket No.: 2333-2 CON II
`
`Page 8
`
`28. (New) The film formulation of claim 19, wherein the ratio of a free base equivalent
`
`amount of said naloxone to the total amount of said one or more polymers is from about 1:2
`
`to about 1:100 by weight.
`
`Page 8
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`Page 8
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`

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`Applicants: Myers et al.
`Serial No.: 13/964,975
`
`Filing Date: August 12, 2013
`Docket No.: 2333-2 CON II
`
`Page 9
`
`REMARKS
`
`Claims 1-24 were originally presented in the application.
`
`Claims 1, 7, 13, and 19 have been amended as shown above. Claims 25-28 have been
`
`added. Support for these amendments and claims can be found throughout the specification,
`
`at for example, paragraphs 0066 and 0067, and in Tables 1 and 5.
`
`No new matter has been added.
`
`Interview Summary
`
`The Examiner is thanked for the courtesies extended during the telephonic interviews
`
`conducted on December 16 and 19, 2013. During the interviews, agreement was reached that
`
`the claim amendments shown above would overcome the sole rejection of the claims over
`
`Oksche et al., US. Patent No.2010/0087470 or WO 2008/025791.
`
`35 U.S.C.
`
`103 Re'ection
`
`Claims 1-24 have been rejected under 35 U.S.C. § 103 as allegedly obvious over
`
`Oksche.
`
`Oksche discloses buprenorphine dosage forms and that naloxone may be present
`
`therein. Oksche also generally discloses that the dosage form may be films, but fails to
`
`provide any disclosure of how to make such films including both buprenorphine and
`
`naloxone. Moreover, Oksche is completely devoid of any teaching of Cmax values for
`
`naloxone. Thus, Oksche does not teach or suggest how to achieve the claimed Cmax values for
`
`buprenorphine and naloxone alone or in combination in a film composition. In addition,
`
`Oksche does not provide any direction as to how to achieve a non-divertible film that
`
`Page 9
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`Page 9
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`Applicants: Myers et al.
`Serial No.: 13/964,975
`
`Filing Date: August 12, 2013
`Docket No.: 2333-2 CON II
`
`Page 10
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`produces optimized buprenorphine release while simultaneously producing a Cmax for
`
`naloxone that is within the claimed invention. Accordingly, Oksche is insufficient to support
`
`a prima facie rejection of the present claims (prior to amendment) for obviousness.
`
`However, although believed unnecessary, and only in an effort to further prosecution,
`
`independent claims 1, 7, 13, and 19 have been amended as shown above to recite a ratio of
`
`buprenorphine to total polymer. As agreed in the examiner interviews, these amendments
`
`overcome the rejection of the claims as obvious over Oksche. Dependent claims 25-28, which
`
`depend directly from independent claims 1, 7, 13, and 19, respectively, have been added to
`
`recite a ratio of naloxone to total polymer.
`
`Conclusion
`
`In view of the foregoing, it is respectfully submitted that the rejection has been
`
`overcome and that this application is in condition for allowance. Favorable reconsideration
`
`and prompt allowance of the application are earnestly solicited.
`
`No fees are believed to be due with this submission. If any fee is required, the
`
`USPTO is hereby requested and authorized to charge the fee to the Deposit Account No. 08-
`
`2461. Such authorization includes authorization to charge fees for extensions of time, if any,
`
`under 37 CPR § 1.17 and also should be treated as a constructive petition for an extension of
`
`time in this reply or any future reply pursuant to 37 C.F.R. § 1.136.
`
`Page 10
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`Page 10
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`Applicants: Myers et al.
`Serial No.: 13/964,975
`
`Filing Date: August 12, 2013
`Docket No.: 2333-2 CON II
`
`Page 11
`
`Should the Examiner have any questions regarding this response she is urged to
`
`contact the undersigned to address them.
`
`Respectfully submitted,
`
`/Stephen J. Brown/
`Stephen J. Brown
`Registration No.: 43,519
`Attorney for Applicants
`
`HOFFMANN & BARON, LLP
`
`6900 Jericho Turnpike
`Syosset, New York 11791
`(973) 331-1700
`
`Page 11
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