DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . Claims 1-28 filed August 12, 2024 are currently pending.
Priority
Acknowledgement is made of the continuation of Application 17666639 filed 02/08/2022. Application 17666639 is a continuation of Application 16512432 filed 07/16/2019. Application 16512432 claims foreign priority to Application 18184034.9 filed 07/18/2018, Application 18197472.6 filed 09/28/2018 and 18202843.1 filed 10/26/2018.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1-7, 10, 14-15, 20, 22-25 and 28 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Klein (US2015/0246045 published 09/03/2015).
Klein (US2015/0246045 published 09/03/2015) teaches the method of treating patients comprising diabetes and at risk of heart failure comprising administering the DPP-4 inhibitor 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperadin-1-yl)-xanthine, optionally in combination with one or more additional agents (claims 1, 4-5, 7-8, 10). Patients comprising type 2 diabetes are embraced within the methodology of Klein ([0040], [0114-0115]).
As evidenced by paragraph [0083] of Klein, the aforementioned DPP-4 inhibitor corresponds to the claimed linagliptin ([0083]).
Said DPP-4 inhibitor regimen is taught to be effective at reducing the risk of major adverse cardiovascular events including cardiovascular death (claims 1, 4-5, 7-8, 10. Klein further teaches that said linagliptin regimen with optionally an additional agent is effective at treating type 2 diabetes in a subject in a patient having or at risk of having chronic kidney disease such as severe renal impairment or end-stage renal disease ([0112]-[0115]).
Regarding the scope of claims 7, Klein teaches that said linagliptin regimen was art recognized at reducing albuminuria in a subject with type II diabetes ([0038]).
Regarding the limitation of claims 10, 14-15, 20 and 22-25, claims 1, 4-5, 7-8 and 10 of Klein embody a patient being identified as at risk of having the cardiovascular event of heart failure and further comprising diabetes. Said patient is then treated with the DPP-4 inhibitor linagliptin, which reads on the limitations of the claims.
Regarding claim 28, doses of 5 mg of linagliptin are embraced within the methodology of Klein ([0107]-[0109]).
Regarding the capacity of the administered linagliptin regimen of Klein to not increase the risk of hospitalization in the type 2 diabetic patient at risk of major adverse cardiovascular events (claim 3), not increase the risk of renal outcome events (claim 5) or wherein the regimen results in a hazard ration of 1.02 (claims 2, 4, 6) although said properties are not explicitly described in the cited prior art to Klein et al., the compound (linagliptin), the amount (therapeutically effective amount; 5 mg) and the same patient population (type 2 diabetic patient at risk of major adverse cardiovascular events) are identical to that of instantly claimed. Therefore, the property of the linagliptin regimen of Klein to not increase the risk of hospitalization or not increase the risk of real outcome events in the type 2 diabetic patient must necessarily be present in regimen of Klein, because products of identical chemical composition cannot exert mutually exclusive properties when prepared or used in the same manner under the same circumstances. In other words, if the prior art teaches the identical chemical or physical structure of the composition, and the composition is used in the same manner (i.e., administered in the same manner to the same subject, in the same therapeutically effective amount) the properties that Applicant discloses and/or claims must necessarily be present. Furthermore, as stated in MPEP 2112.02, “[u]nder the principles of inherency, if a prior art device, in its normal and usual operation, would necessarily perform the method claimed, then the method claimed will be considered anticipated by the prior art device.”
Claim(s) 1-28 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Johansen et al (US2016/0089373 published 03/31/2016).
Johansen teaches the administration of linagliptin, orally, in a dose of 5 mg to a type 2 diabetic patient comprising a risk of cardiovascular morbidity and renal microvascular disease ([0021], [0027]-[0028], claim 1, 3-4, 13-14).
Regarding the scope of claim 8, Johansen teaches that said regimen is effective at reducing renal and cardiovascular death in said type II diabetic patients ([0031], claims 1, 3-4, 13-14).
Regarding claim 9, Johansen teaches administration of said linagliptin for at least 3 years, which reads on the limitation of “at least 1.9 years” ([0027]-[0028], claims 1, 3-4, 13-14, 23).
Regarding the limitation of claims 10, 14-15, 20 and 22-25, Johansen embodies a patient being identified as at risk of having the cardiovascular event of cardiovascular morbidity and renal disease and further comprising type II diabetes. Said patient is then treated with linagliptin, which reads on the limitations of the claims. Regarding claims 7, 11-13, 16-19, 26-27 Johansen teaches that risk in said patient is based on a history of established macrovascular disease, and wherein the patient comprises a UACR of greater or equal to 30 mg/g, which reads on albuminuria, and wherein the patient had a previous macrovascular disease selected from the group consisting of previous myocardial infarction, advanced coronary artery disease, and an impaired renal function ([0350]-[0354], [0673], claims 1, 3-4, 13, 14).
Regarding the scope of claims 3-4, 21, Johansen teaches that said linagliptin regimen reduces hospitalizations for cardiac events in said patient ([0114], claims 1, 3-5).
Regarding the capacity of the administered linagliptin regimen of Johansen to not increase the risk of renal outcome events (claim 5) or wherein the regimen results in a hazard ration of 1.02 (claims 2, 4, 6) although said properties are not explicitly described in the cited prior art to Johansen et al., the compound (linagliptin), the amount (therapeutically effective amount; 5 mg) and the same patient population (type 2 diabetic patient at risk of major adverse cardiovascular and renal events) are identical to that of instantly claimed. Therefore, the property of the linagliptin regimen to not increase the risk of hospitalization or not increase the risk of real outcome events in the type 2 diabetic patient must necessarily be present in regimen of Johansen, because products of identical chemical composition cannot exert mutually exclusive properties when prepared or used in the same manner under the same circumstances. In other words, if the prior art teaches the identical chemical or physical structure of the composition, and the composition is used in the same manner (i.e., administered in the same manner to the same subject, in the same therapeutically effective amount) the properties that Applicant discloses and/or claims must necessarily be present. Furthermore, as stated in MPEP 2112.02, “[u]nder the principles of inherency, if a prior art device, in its normal and usual operation, would necessarily perform the method claimed, then the method claimed will be considered anticipated by the prior art device.”
Claim(s) 1-28 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Meinicke et al (US2017/0354660 published 12/14/2017).
The applied reference has a common inventor and assignee (M. Von Eynatten; Boehringer Ingelheim) with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
Meinicke teaches the method of treating type II diabetes in a subject comprising administering a therapeutically effective amount of linagliptin in combination with metformin. Meinicke teaches that said regimen is effective at slowing the renal impairment of albuminuria and cardiovascular events (non-fatal myocardial infarction, non-fatal stroke) in said type II diabetic patient (claims 1-3). Meinicke teaches that said combination therapy protects against end-stage renal disease and loss of estimated glomerular filtration rate (eGFR >50%) (claims 1-3). Treatment of a patient for at least 3 years is embraced by Meinicke, which reads on the dosing frequency of claim 9 (claim 22).
Meinecke teaches that the patient comprises albuminuria with a UACR of >30 mg/g creatinine, and comprises previous myocardial infarctions, which read on the patient population embraced in instant claims 12-13, 17-19 and 26-27 (claims 2-3, 20-21). Regarding the limitation of claims 10, 14-15, 20 and 22-25, claims 1-3, 20-21 of Meinicke embody a patient being identified as at risk of having a cardiovascular event (non-fatal stroke, non-fatal myocardial infarction), the renal complication of albuminuria and further comprising type II diabetes. Said patient is then treated with linagliptin and metformin, which reads on the limitations of the claims. Regarding claim 28, doses of 5 mg of linagliptin are embraced within the methodology of Meinicke (claim 5).
Regarding the capacity of the administered linagliptin regimen of Meinicke to not increase the risk of hospitalization in the type 2 diabetic patient at risk of major adverse cardiovascular events (claim 3), not increase the risk of renal outcome events (claim 5) or wherein the regimen results in a hazard ration of 1.02 (claims 2, 4, 6) although said properties are not explicitly described in the cited prior art to Meinicke et al., the compounds (linagliptin/metformin), the amount (therapeutically effective amount; 5 mg) and the same patient population (type 2 diabetic patient at risk of major adverse cardiovascular and renal events) are identical to that of instantly claimed. Therefore, the property of the linagliptin/metformin regimen of Meinicke to not increase the risk of hospitalization or not increase the risk of real outcome events in the type 2 diabetic patient must necessarily be present in regimen of Meinicke, because products of identical chemical composition cannot exert mutually exclusive properties when prepared or used in the same manner under the same circumstances. In other words, if the prior art teaches the identical chemical or physical structure of the composition, and the composition is used in the same manner (i.e., administered in the same manner to the same subject, in the same therapeutically effective amount) the properties that Applicant discloses and/or claims must necessarily be present. Furthermore, as stated in MPEP 2112.02, “[u]nder the principles of inherency, if a prior art device, in its normal and usual operation, would necessarily perform the method claimed, then the method claimed will be considered anticipated by the prior art device.”
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 20-22 of U.S. Patent No. 10,155,000 in view of Klein (US2013/0303462 published 11/14/2013).
Claims 1-5 of US Patent 10,155,000 are directed to the treatment of treating chronic kidney disease in a type II diabetic patient comprising administering an effective amount of linagliptin and metformin. Said chronic kidney diseased patient comprises an estimated glomerular filtration rate (eGFR) of 60-30mL/min per 1.73m2 , which reads on the patient’s impaired renal function in instant claim 19. Administration of a dose of 5 mg of linagliptin is embraced in the methodology of US Patent 10,155,000, which overlaps with the amount embodied in instant claim 28. US Patent 10,155,000 teaches that said regimen reduces the risk of the same cardiovascular complications embraced in instant claims 1 (claim 3).
However, instant claims do not specifically teach wherein the additional agent is metformin.
Klein teaches the combination of linagliptin with metformin to treat type II diabetic patients with diabetic nephropathy wherein said patients comprised an eGFR of >30 mL/min with 1.73m2 ([0332]). Klein teaches that the resulting combination of linagliptin and metformin yielded kidney protecting properties in the patient ([0332]).
Accordingly, a skilled artisan would have found it prima facie obvious to combine metformin to the regimen embraced in instant claims 1-28 in view of Klein in order to arrive at the methodology of claims 1-5 in US Patent 10,155,000. Motivation to add metformin to the linagliptin regimen logically flows from the fact that the combination of metformin and linagliptin was recognized in the art to comprise kidney protecting properties in type II diabetic patients with diabetic nephropathy in view of Klein.
Regarding the capacity of the administered linagliptin and metformin regimen of US Patent 10,155,000 and Klein to not increase the risk of hospitalization in the type 2 diabetic patient at risk of major adverse cardiovascular events (claim 3), not increase the risk of renal outcome events (claim 5) or wherein the regimen results in a hazard ration of 1.02 (claims 2, 4, 6) although said properties are not explicitly described in the cited prior art of US Patent 10,155,000 and Klein et al., the compounds (linagliptin and metformin), the amount (therapeutically effective amount; 5 mg) and the same patient population (type 2 diabetic patient at risk of major adverse cardiovascular and renal events) are identical to that of instantly claimed. Therefore, the property of the linagliptin and metformin regimen of US Patent 10,155,000 and Klein to not increase the risk of hospitalization or not increase the risk of real outcome events in the type 2 diabetic patient must necessarily be present in the combined regimen, because products of identical chemical composition cannot exert mutually exclusive properties when prepared or used in the same manner under the same circumstances. In other words, if the prior art teaches the identical chemical or physical structure of the composition, and the composition is used in the same manner (i.e., administered in the same manner to the same subject, in the same therapeutically effective amount) the properties that Applicant discloses and/or claims must necessarily be present.
It is noted that MPEP 2112 discusses the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on" (205 USPQ 594, second column, first full paragraph). In the present case the burden is shifted to Applicant to prove that the combined linagliptin and metformin regimen embraced in claims 1-5 and 20-22 of US Patent 10,155,000 and Klein will not reduce the risk of hospitalization in the type II diabetic patient comprising cardiovascular and/or renal complications.
Conclusion
In view of the rejections set forth above, no claim is allowed.
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/GEORGE W KOSTURKO/Primary Examiner, Art Unit 1621
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