Docket No.: AGP-002C3
`(PATENT)
`
`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`In re Patent Application of:
`Daniel J. Rader
`
`Application No.: 14/075,483
`
`Confirmation No.: 4350
`
`Filed: November 8, 2013
`
`Art Unit: 1629
`
`For: METHODS FOR TREATING DISORDERS OR
`DISEASES ASSOCIATED WITH
`HYPERLIPIDEMIA AND
`HYPERCHOLESTEROLEMIA WHILE
`MINIMIZING SIDE EFFECTS
`
`Examiner: K. E. Weddington
`
`AMENDMENT AND RESPONSE TO FINAL OFFICE ACTION
`
`MS Amendment
`Commissioner for Patents
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`This Response is being filed in response to the outstanding Office Action, mailed May
`
`28, 2015, in connection with the above-identified application, together with a Certification and
`
`Request for Prioritized Examination, a Request for Continued Examination, a Declaration under 3 7
`
`C.P.R. §1.131, an Information Disclosure Statement, a form PTO/SB/08, copies of references cited
`
`thereon, and a petition for an extension of time.
`
`Amendments to the Claims begin on page 2 of this paper.
`
`Remarks begin on page 6 of this paper.
`
`Page 1 of 9
`
`PENN EX. 2005
`CFAD V. UPENN
`IPR2015-01836
`
`
`(PATENT)
`
`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`In re Patent Application of:
`Daniel J. Rader
`
`Application No.: 14/075,483
`
`Confirmation No.: 4350
`
`Filed: November 8, 2013
`
`Art Unit: 1629
`
`For: METHODS FOR TREATING DISORDERS OR
`DISEASES ASSOCIATED WITH
`HYPERLIPIDEMIA AND
`HYPERCHOLESTEROLEMIA WHILE
`MINIMIZING SIDE EFFECTS
`
`Examiner: K. E. Weddington
`
`AMENDMENT AND RESPONSE TO FINAL OFFICE ACTION
`
`MS Amendment
`Commissioner for Patents
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`This Response is being filed in response to the outstanding Office Action, mailed May
`
`28, 2015, in connection with the above-identified application, together with a Certification and
`
`Request for Prioritized Examination, a Request for Continued Examination, a Declaration under 3 7
`
`C.P.R. §1.131, an Information Disclosure Statement, a form PTO/SB/08, copies of references cited
`
`thereon, and a petition for an extension of time.
`
`Amendments to the Claims begin on page 2 of this paper.
`
`Remarks begin on page 6 of this paper.
`
`Page 1 of 9
`
`PENN EX. 2005
`CFAD V. UPENN
`IPR2015-01836
`
`
`
`Application No. 14/075,483
`Attorney Docket No.: AGP-002C3
`Amendment and Response to Office Action
`Page2of6
`
`AMENDMENTS TO THE CLAIMS
`
`What is claimed is:
`
`1.
`
`(Previously presented) A method of treating a subject suffering from hyperlipidemia or
`
`hypercholesterolemia, the method comprising administering to the subject an effective amount of an
`
`MTP inhibitor, wherein said administration comprises at least three step-wise, increasing dose
`
`levels of the MTP inhibitor wherein the dose levels are from about 2 to about 13 mg/day, from
`
`about 5 to about 30 mg/day, and from about 10 to about 50 mg/day; and wherein the MTP inhibitor
`
`is represented by:
`
`or a pharmaceutically acceptable salt thereof or the piperidine N-oxide thereof, and wherein each
`
`dose level is administered to the subject for about 1 to about 5 weeks.
`
`2.
`
`(Original) The method of claim 1 wherein the disorder is severe hypercholesterolemia.
`
`Page 2 of 9
`
`PENN EX. 2005
`CFAD V. UPENN
`IPR2015-01836
`
`
`
`Application No. 14/075,483
`Attorney Docket No.: AGP-002C3
`Amendment and Response to Office Action
`Page3 of6
`
`3.
`
`(Original) The method of claim 1 wherein one or more of Total Cholesterol, LDL, fasting
`
`triglycerides (TG), VLDL, lipoprotein (a) (Lp(a)), and apolipoproteins A-I, A-II, B, and E are
`
`reduced by at least 15%, compared to control levels.
`
`4.
`
`(Original) The method of claim 1 wherein one or more of Total Cholesterol, LDL, fasting
`
`triglycerides (TG), VLDL, lipoprotein (a) (Lp(a)), and apolipoproteins A-I, A-II, B, and E are
`
`reduced by at least 25%, compared to control levels.
`
`5.
`
`6.
`
`7.
`
`8.
`
`(Cancelled)
`
`(Original) The method of claim 1 wherein the MTP inhibitor is administered orally.
`
`(Cancelled)
`
`(Previously presented) The method of claim 1 wherein said increasing dose levels further
`
`comprise a fourth dose level.
`
`9. - 25. (Cancelled)
`
`26.
`
`(New) A method of treating a subject suffering from hyperlipidemia or
`
`hypercholesterolemia, the method comprising administering to the subject an effective amount of an
`
`MTP inhibitor, wherein said administration comprises at least three step-wise, increasing dose
`
`levels of the MTP inhibitor up to a maximum dose level, wherein a first starting dose level is from
`
`about 2 to about 13 mg/day, a second dose level is from about 5 to about 30 mg/day, and a third
`
`dose level is from about 10 to about 50 mg/day; and wherein the MTP inhibitor is represented by:
`
`Page 3 of 9
`
`PENN EX. 2005
`CFAD V. UPENN
`IPR2015-01836
`
`
`
`Application No. 14/075,483
`Attorney Docket No.: AGP-002C3
`Amendment and Response to Office Action
`Page4of6
`
`or a pharmaceutically acceptable salt thereof or the piperidine N-oxide thereof, and wherein each
`
`dose level is administered to the subject for about 1 to 4 weeks, wherein upon administration the
`
`patient has reduced steatorrhea as compared to a patient administered a starting dose of25 mg/day.
`
`27.
`
`(New) The method of claim 26, wherein the administering increasing dose levels further
`
`comprises a fourth dose level of about 20 to about 60 mg/day and a maximum dose level of about
`
`30 to about 75 mg/day.
`
`28.
`
`(New) A method of treating a subject suffering from hyperlipidemia or
`
`hypercholesterolemia, the method comprising administering to the subject an effective amount of an
`
`MTP inhibitor, wherein said administration comprises at least three step-wise, increasing dose
`
`levels of the MTP inhibitor, wherein a first dose level is from about 2 to about 13 mg/day, a second
`
`dose level is from about 5 to about 30 mg/day, and a third dose level is from about 10 to about 50
`
`mg/day; and wherein the MTP inhibitor is represented by:
`
`Page 4 of 9
`
`PENN EX. 2005
`CFAD V. UPENN
`IPR2015-01836
`
`
`
`Application No. 14/075,483
`Attorney Docket No.: AGP-002C3
`Amendment and Response to Office Action
`Page5 of6
`
`or a pharmaceutically acceptable salt thereof or the piperidine N-oxide thereof, and wherein each
`
`dose level is administered to the subject for about 1 to 4 weeks, wherein the method reduces
`
`symptoms of steatorrhea and/or hepatic fat in the subject.
`
`29.
`
`(New) The method of claim 28, wherein the administering increasing dose levels further
`
`comprises a fourth dose level of about 20 to about 60 mg/day and a maximum dose level of about
`
`30 to about 75 mg/day.
`
`Page 5 of 9
`
`PENN EX. 2005
`CFAD V. UPENN
`IPR2015-01836
`
`
`
`Application No. 14/075,483
`Attorney Docket No.: AGP-002C3
`Amendment and Response to Office Action
`Page6of6
`
`REMARKS
`
`Claims 1-4, 6, 8 and 26-29 are pending. Claims 26-28 are new. Support for new claims 26-
`
`29 is found throughout the application as filed, including, for example, at paragraphs 24, 58, 63, and
`
`in Example 8 (see pages 26-27). No new matter has been added.
`
`Applicant further submits herewith a Declaration under 37 C.P.R. §1.131 by inventor Daniel
`
`J. Rader which may be useful for consideration by the Office.
`
`Double Patenting
`
`Claims 2-9 and 11-13 stand rejected on the ground of nonstatutory obviousness-type double
`
`patenting as being unpatentable over claims 2-8 of U.S. Patent No. 7,932,268. Applicant is
`
`concurrently filing an e-terminal disclaimer to obviate the rejection. Applicant respectfully requests
`
`the rejection be reconsidered and withdrawn.
`
`Claims 1-18 and 20-23 stand rejected on the ground of nonstatutory obviousness-type
`
`double patenting as being unpatentable over claims 1-10 ofU.S. Patent No. 8,618,135. Applicant is
`
`concurrently filing an e-terminal disclaimer to obviate the rejection. Applicant respectfully requests
`
`the rejection be reconsidered and withdrawn.
`
`Any questions raised by this submission may be directed to the undersigned at (617) 570-
`
`3917. The Commissioner is hereby authorized to charge any underpayments, or credit any
`
`overpayments, to our Deposit Account No. 07-1700, Reference: AGP-002C3.
`
`Dated: November 30,2015
`
`Respectfully submitted,
`
`/Megan A. Gustafson/
`Megan A. Gustafson
`Registration No.: 65,847
`GOODWIN PROCTER LLP
`Exchange Place
`Boston, Massachusetts 021 09
`(617) 570-1000
`Attorney for Applicant
`
`Page 6 of 9
`
`PENN EX. 2005
`CFAD V. UPENN
`IPR2015-01836
`
`
`
`Docket No.: AGP-002C3
`(PATENT)
`
`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`In re Patent Application of:
`Daniel J. Rader
`
`Application No.: 14/075,483
`
`Confirmation No.: 4350
`
`Filed: November 8, 2013
`
`Art Unit: 1629
`
`For:
`
`lviETHODS FOR TREATING DISORDERS OR
`DISEASES ASSOCIATED WITH
`HYPERLIPIDEMIA AND
`HYPERCHOLESTEROLEMIA WHILE
`MINIMIZING SIDE EFFECTS
`
`Examiner: K. E. Weddington
`
`DECLARATION UNDER 37 C.F.R. §1.131
`
`I, Daniel J. Rader, hereby declare as follows:
`
`1.
`
`I am the inventor of the claimed subject matter of the above-identified patent. I
`
`am employed by the University of Pennsylvania as the Seymour Gray Professor of Molecular
`
`Medicine~ the Chair of the Department of Genetics~ the Chief of the Division of Translational
`
`Medicine and Human Genetics~ and the Associate Director for the Institute for Translational
`
`Medicine and Therapeutics. I have assigned my rights in the invention to the University of
`
`Pennsylvania ("the University").
`
`2.
`
`I conceived, and reduced to practice, in the United States, the subject matter
`
`claimed in the above-referenced patent application at least prior to February 4, 2004, as
`
`evidenced by the materials attached as Exhibit AI.
`
`3.
`
`Exhibit Al is a copy of a confidential electronic message I prepared and sent on
`
`Thursday, January 8, 2004, to the Chair of the Data Safety Monitoring Board for a clinical trial
`
`entitled "Open Label, Dose Escalation Study to Determine the Safety, Tolerability and
`
`Efficacy of Microsomal Triglyceride Transfer Protein (MTP) Inhibitor BMS-201038 in
`
`Patients with Homozygous Familial Hypercholesterolemia." This clinical protocol used a step(cid:173)
`
`wise, increasing dose approach, as in the pending claims, with the compound BMS-201038 to
`
`ACTIVE/84060036.6
`
`Page 7 of 9
`
`PENN EX. 2005
`CFAD V. UPENN
`IPR2015-01836
`
`
`
`treat patients suffering from homozygous familial hypercholesterolemia.
`
`I note that BMS-
`
`201038 is the compound pictorially represented in the pending independent claims.
`
`4.
`
`My email correspondence of Exhibit Al evidences my prior conception and
`
`reduction to practice of the invention described in the above captioned patent application,
`
`including the efficacy and tolerability of the dose escalation protocol used during the trial and
`
`described in the instant pending claims at least prior to February 4, 2004.
`
`5.
`
`I declare that all statements made herein of my own knowledge are true and that
`
`all statements made on information and belief are believed to be true; and further that these
`
`statements were made with the knowledge that willful false statements and the like so made are
`
`punishable by fine or imprisonment, or both, under Section 1001 of Title 18 of the United
`
`States Code, and that such willful false statements may jeopardize the validity of the
`
`application or any patent issuing thereon.
`
`ACTIVE/84060036.6
`
`2
`
`Page 8 of 9
`
`PENN EX. 2005
`CFAD V. UPENN
`IPR2015-01836
`
`
`
`Kathleen Yerger
`
`From;
`~ent:
`
`Cc:
`Subject:
`
`Dan Rader [rader@mai!.med.upenn.edu]
`08, 2004 11 :46 AM
`
`Exhibit Al
`
`c.omElS off
`As a reminde:r, 3 patients have completed the st.u
`drug early next week, and the 5th and 6th
`came off
`lity of the
`late next week. Overall, we are very encour
`drug and anxious to fully evaluate the efficacy regarding cholesterol lowering.
`
`Thanks a~rain.
`
`Dan_
`
`.1
`
`Page 9 of 9
`
`PENN EX. 2005
`CFAD V. UPENN
`IPR2015-01836
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