U.S. Application No.: 14/161,007
`Response to Final Office Action dated April 16, 2015
`Attorney Docket No.: 01-2051-US-3
`
`REMARKS
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`Claims 15, 17-19, 24, 25, 27-32, 35-42 were pending in the subject application. In
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`this amendment Applicants have added new claims 43 and 44. Claims 15, 17-19, 24, 25,
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`27-32, 35-44 are now pending in the subject application.
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`New claims 43 and 44 depend from claims 24 and 25, respectively, and further
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`specify that the 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methy1-7-(2-butyn-1-yl)-8-(3-(R)-
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`amino-piperidin-1-yl)-xanthine is administered in a twice daily dose (claim 43) or once
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`daily dose (claim 44). Support for new claims 43 and 44 can be foundin the original
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`specification at, for example, page 14, first paragraph.
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`No new matter is added by this amendment, and Applicants respectfully requestits
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`entry.
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`I.
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`Non-statutory Double Patenting Rejections
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`A.
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`Rejection of Claim 15 over Claims 1-9 of U.S. Patent No. 8,119,648 B2
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`The Examiner rejected claim 15 on the ground of nonstatutory obviousness-type
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`double patenting as allegedly being unpatentable over claims 1-9 of U.S. Patent No.
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`8,119,648 B2 for the reasonsset forth in the previousoffice action at pages 2-4 (“the
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`November 19, 2014 office action”). In the November 19, 2014 office action, the Examiner
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`stated that“the claims at issue are not identical, they are not patentably distinct from each
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`other because the only difference between the patented claims and the present claim lies in
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`that in the present claims, the addition of metformin with the 1-[(40methyl-quinazolin-2-
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`yl)methyl]-3-methyl-7-(2-butyn-1-yi)-8-(3-(R)-amino-piperidin-1-yl)-xanthine. The
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`present claim would anticipate the patented claims because the patented claimsrecite
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`‘comprising’ and thus opens the claims to the inclusion of metformin.”
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`Applicants traverse. Claims 1-9 of the ‘648 patent relate inter alia to a method of
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`treating type II diabetes mellitus comprising administering a pharmaceutically effective
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`amount of 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn- 1-yl)-8-(3-(R)-
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`amino-piperidin-1-yl)-xanthine to a patient in need thereof. The Examinerasserts that the
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`term “comprising” in the claims 1-9 of the ‘648 patent “opens the claims to the inclusion
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`of metformin.” However, even if the term “comprising” in claims 1-9 of the ‘648 patent
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`includes metformin as stated by the Examiner, none of claims 1-9 of the ‘648 patent
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`

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`U.S. Application No.: 14/161,007
`Response to Final Office Action dated April 16, 2015
`Attorney Docket No.: 01-2051-US-3
`
`specifies the oral dosage of 2.5 mg or 5 mg of 1-[(4-methyl-quinazolin-2-yl)methy]]-3-
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`methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine nor do they recite the
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`specific daily dosage amounts metformin, nor that the metformin can be administered to
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`the patient either once, twice or three times a day. Thus, the patented claims do not
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`anticipate the present claims. Further, as already discussed in the previous responsive
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`amendmentfiled on February 18, 2015, the Prescribing Information and Patient
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`Information for TRADJENTA®(linagliptin) having a revision date of 9/2012
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`(“Prescribing Information”) showsthat significant improvements in A1C and FPG were
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`achieved using 2.5 mg linagliptin twice daily and either 500 mg or 1000 mg metformin
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`twice daily. Therefore, one skilled in the art would not have plainly expected or predicted
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`that the specific dosage amounts of linagliptin and metformin in a combination therapy
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`would provide the (clinically and therapeutically) significant improvements in A1C and
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`FPG asreported in the clinical study section of the Prescribing Information.
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`Atleast in view of these unexpected clinical properties, Applicants respectfully
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`submit that the rejection based on obviousness-type double patenting as to the “648 patent
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`has been overcome. See Eli Lilly v. Teva Parenteral Medicines, Inc., 689 F.3d 1368, 1382
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`(Fed, Cir. (2012) (“The district court's categorical repudiation of Lilly's evidence [of
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`unexpected clinical properties and commercial success] was therefore erroneous. When
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`offered, such evidence should be considered; a fact-finder must withhold judgment on an
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`[obviousness-type double patenting] challenge until it has considered all relevant evidence,
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`including that relating to the objective considerations.”’)
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`B.
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`Rejection of Claims 15, 17-19, 24, 25, 27-32 and 35-42 over Claims 1-9
`of U.S. Patent No. 8,178,541 B2
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`The Examiner rejected claims 15, 17-19, 24, 25, 27-32 and 35-42 on the ground of
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`nonstatutory obviousness-type double patenting as allegedly being unpatentable over
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`claims 15, 32, 35, 36, 39, 41 and 45 of U.S. Patent No. 8,178,541 B2 for the reasons set
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`forth on pages 4-5 of the November 19, 2014 office action. In the November 19, 2014
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`office action the Examinerstates that “‘[a]lthough the claimsat issue are not identical, they
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`are not patentably distinct from each other because the present application teaches a
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`methodfor treating type 2 diabetes with a composition comprising 1-[(4-methyl-
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`quinazolin-2-yl)methy]]-3-methyl-7-(2-butyn-1-yi)-8-(3-(R)-amino-piperidin-1-yl)-
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`

`

`U.S. Application No.: 14/161,007
`Response to Final Office Action dated April 16, 2015
`Attorney Docket No.: 01-2051-US-3
`
`xanthine and metformin, and the patented application teaches a method for treating type IT
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`diabetes or obesity with 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methy1-7-(2-butyn-1-yi)-
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`8-(3-(R)-amino-piperidin- 1-yl)-xanthine and another therapeutic agent such as metformin.”
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`The Examinerasserts that “the patented application teaches the present application's instant
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`combination for the treatment of type 2 diabetes.”
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`Applicants traverse. Claims 15, 32, 35, 36, 39, 41 and 45 of the ‘541 patent relate
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`inter alia to a methodoftreating type II diabetes mellitus comprising administering a
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`pharmaceutically effective amount of 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-
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`butyn-1-yl)-8-(3-(R)-amino-piperidin- 1-yl)-xanthine and a pharmaceutically effective
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`amount of metformin to a patient in need thereof. The Examinerasserts that “the patented
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`application teaches the present application's instant combination for the treatment of type 2
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`diabetes.” However, even if claims 15, 32, 35, 36, 39, 41 and 45 of the ‘541 patent recite a
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`combination therapy of 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn- 1-yl)-
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`8-(3-(R)-amino-piperidin-1-yl)-xanthine and metformin, none of those claims of the ‘541
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`patent specify the oral dosage of 2.5 mg or 5 mg of 1-[(4-methyl-quinazolin-2-yl)methyl]-
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`3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin- 1-yl)-xanthine nor do they recite the
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`specific daily dosage amounts metformin, nor that the metformin can be administered to
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`the patient either once, twice or three times a day. As noted above, significant
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`improvements in A1C and FPG were achieved using 2.5 mg linagliptin twice daily and
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`either 500 mg or 1000 mg metformin twice daily. One skilled in the art would not have
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`plainly expected or predicted that the specific dosage amountsof linagliptin and metformin
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`in a combination therapy would provide the (clinically and therapeutically) significant
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`improvements in AIC and FPG asreported in the clinical study section of the Prescribing
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`Information based on claims 15, 32, 35, 36, 39, 41 and 45 of the ‘541 patent.
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`In summary, Applicants submit that these unexpected clinical properties have
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`overcome the obviousness-type double patenting rejection in accordance with Eli Lilly v.
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`Teva Parenteral Medicines, Inc. Vherefore, Applicants request that the obviousness type-
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`double patenting rejection as to the ‘541 patent be withdrawn.
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`C.
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`Rejection of Claims 15-40 over Claims 1-26 of U.S. Patent No. 8,673,927
`B2
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`

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`U.S. Application No.: 14/161,007
`Response to Final Office Action dated April 16, 2015
`Attorney Docket No.: 01-2051-US-3
`
`The Examinerrejected claims 15-40 on the ground of nonstatutory obviousness-
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`type double patenting as allegedly being unpatentable over claims 1-26 of U.S. Patent No.
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`8,673,927 B2 for the reasonsset forth in the present office action. Applicants note that
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`claims 15, 17-19, 24, 25, 27-32, 35-42 are presently pending in the subject application
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`Submitted herewith is a Terminal Disclaimeras to the ‘927 patent. Applicants
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`submit that the submission of this Terminal Disclaimer fully addresses the Examiner's
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`obviousness-type double-patenting rejection of pending claims 15, 17-19, 24, 25, 27-32,
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`35-42 as to the ‘927 patent.
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`CONCLUSION
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`Applicants respectfully request prompt consideration of the pending claims and
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`allowance of the application. No additional fee is believed due. However, if any
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`additional fee is due, the Examiner is authorized to charge the fee to Applicants’ Deposit
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`Account No. 02-2955.
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`If a telephonic or personal interview is deemed necessary to expedite the examination
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`of the instant application, the Examiner is kindly requested to contact the undersigned at the
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`telephone numberlisted below.
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`Respectfully submitted,
`
`/David L. Kershner/
`David L. Kershner
`Attorney for Applicant(s)
`Reg. No. 53,112
`
`Patent Department
`Boehringer Ingelheim Corp.
`900 Ridgebury Road
`P.O. Box 368
`Ridgefield, CT 06877
`Tel.:
`(203) 798-5469
`Fax: (203) 798-4408
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`Date: July 10, 2015
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