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 1-11 are pending and under examination.
Information Disclosure Statement
The Information Disclosure Statements (IDSs) filed on 1/10/2024 and 9/17/2025 have been considered.
Priority
The Instant application is a CON of US Application No. 17/599,621 filed on 11/4/2019.
Claim Rejections - 35 USC § 102
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, 2 and 6-9 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bauduceau (IDS, Medicine des malides metabolidquies 13: 55-62, 2019 (Feb).
The instantly claimed invention is broadly drawn to a method of reducing the risk of major adverse cardiovascular events in a patient with type 2 diabetes mellitus, comprising administering dulaglutide in a therapeutically effective amount to the patient once weekly, wherein the patient has type 2 diabetes mellitus and either:(a) multiple cardiovascular risk factors without established cardiovascular disease; or (b) established cardiovascular disease, wherein the CV risk is LDL-C measured within six month and is ≥ to 130 mg/dL, and wherein the therapeutically effective amount of dulaglutide is 1.5 mg.
It is noted that the limitations of claim 10 is an intended use and it does not carry any patentable weight.
Bauduceau teaches administering dulaglutide (Trulicity) in an amount of 1.5 mg in type 2 diabetic subject (summary). Bauduceau compared its effectiveness regarding cardiovascular outcome against GLP-1 receptor agonists e.g., liraglutide, exenatide and others (summary). Therefore, the instantly claimed invention is implicitly or explicitly anticipated by the prior art of record.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 1-11 are rejected under 35 U.S.C. 103 as being unpatentable over Bauduceau (IDS, Medicine des malides metabolidquies 13: 55-62, 2019 (Feb) over Boyle et al (IDS, Clinical Science, 2018), Oshima et al. (IDS, EP 3275438), and Ferdinand et al. (IDS, Cardiovasc. Diabetol. 15: 38 (2016)).
The instantly claimed invention is broadly drawn to use of dulaglutide in a therapeutically effective amount once weekly for reducing the risk of major cardiovascular (CV) events in a patient with type 2 diabetes mellitus having multiple CV risk factors without established CV disease, wherein the CV risk is LDL-C measured within six month and is ≥ to 130 mg/dL, or TG>200 mg/dL, wherein the therapeutically effective amount of dulaglutide is 1.5 mg, wherein the method reduces the risk of a major adverse CV event by at least 10%, wherein the once-weekly administration is for approximately 5 years and the method further comprises administering ACE inhibitor, ARB, aspirin or a statin.
Bauduceau teaches administering dulaglutide (Trulicity) in an amount of 1.5 mg in type 2 diabetic subject (summary). Bauduceau compared its effectiveness regarding cardiovascular outcome against GLP-1 receptor agonists e.g., liraglutide, exenatide and others (summary). They do not teach identifying diabetic subject having (a) multiple CV risk factors without established CV disease or (b) established CV disease and the limitations of claim 4.
Boyle et al. teach that GLP-1 agonists provide cardiovascular benefits in type 2 patients (abstract). They teach that GLP-1 agonists provide glucose lowering effect in diabetic patients and that the lowering blood glucose also results in lowering macrovascular complications (abstract). They teach that GLP-1 agonist reduces body weight, plasma lipids and plasma glucose and all of these are cardiovascular risk factor (see Figure 1). They looked liraglutide results in type 2 diabetics with liraglutide 1.8 mg once daily treatment provides superior benefit myocardial infarction and stroke (see pg. 1703, Main results (CV outcomes)). They teach that some clinical trials have done for at least 6 years. They compared liraglutide with semaglutide and other GLP-1 agonists and explained that all experiments were not performed for same period and that the structure of compound is different. They teach that GLP-1 agonists which work through GLP-1 receptor and treated for 24 hours results in reduction (or strong trends towards reduction) in rates of CV events and as some of these effects may be mediated by reduction in body weight, blood pressure, cholesterol and HbA1c (A class effect, pg. 1705). They teach administering dulaglutide 1.5 mg/week in type 2 diabetes patients (Table 2, and REWIND). They do not teach administering statin or ACE inhibitors for reducing CV risk factors such as TG..
Oshima et al teach preventing cardiovascular event and treating patients with dyslipidemia (abstract). They teach reducing risk of cardiovascular disease and adverse CV events in patients on intense statin use or well controlled LDL-C concentration (abstract). They teach that dyslipidemia is characterized by an imbalance in person’s lipid metabolism and that results in higher risk of CV diseases. They teach that in dyslipidemia a person comprises higher LDL, triglyceride and low level of HDL. They patients with dyslipidemia may be on a number of statins such as Atorvastatin, Rosuvastatin, Lovastatin for controlling LDL but still their TG may be higher than 200 mg/dL ( paragraph [0021], [0049], [0055]). They teach to use various statins, ACE inhibitors, aspirin, angiotensin-receptor blockers (ARB) for CV treatment in addition to dulaglutide (see pg. 23, 42)-50). They teach treating dyslipidemia with a glucagon-like peptide such as dulaglutide (pg. 23, 52(e)). Neither Bauduceau, Boyle nor Oshima teaches reduction in the risk of major adverse event by at least 10%.
Ferdinand et al. (IDS, Cardiovasc. Diabetol. 15: 38 (2016)) teach CV safety evaluation of dulaglutide once-weekly dose in type 2 diabetic subjects. They included a large number of patients (about 3885) found that weekly administration of dulaglutide for a long period of time (at least 2 years) reduces the risk of nonfatal MI compared to similar GLP-1 agonists (see pg. 6 of 12, right col., Fig. 1). Because the reduction of risk factor is only studied for 2 years, it would be obvious to one skill in the art that over a period of time, for example 5 years, 10 years or 15 years, the reduction of risk factors with dulaglutide would be at least 10% or so.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to use dulaglutde (Trulicity) for a period of 5 or more years to see the beneficial effect of dulaglutide over the CV risk factors as taught by Ferdinand et al and to use a composition comprising dulaglutide in combination with a statin, ACE inhibitor, ARB, or aspirin for lowering a CV risk factor as taught by Oshima et al in treating a patient having type 2 diabetes that comprises CV risk factor by administering dulaglutide as taught by Boyle et al. and wherein the administration of dulaglutide is 1.5 mg as taught by Bauduceau. Additionally, one would have been motivated to do so because Ferdinand et al teach that dulaglutide reduces cardiovascular risk as compared to other GLP-1 agonist and Oshima et al teach that dulaglutide reduces CV risk factor including triglyceride. Additionally, Oshima et al teach that dulaglutide can be used for patient who have using ACE inhibitor, statin or ARB to lower lipids, or to lower blood pressure. Boyle emphasized that GLP-1 in general reduce blood pressure, body weight and blood glucose which are also CV risk factors. Further, one would have a reasonable expectation of success in using dulaglutide (Trulicity) as taught by Boyle et al, Oshima et al., Ferdinand to treat a diabetic subject over a long period of time to reduce CV risk factors and Bauduceau teaches effectiveness of dulaglutide regarding cardiovascular outcome against GLP-1 receptor agonists e.g., liraglutide, exenatide and others (summary). Therefore, the instantly claimed invention would have obvious to one skill in the art over the combined teaching of the prior art of record.
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 1-11 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 11,890,325. Although the claims at issue are not identical, they are not patentably distinct from each other because a method of reducing the risk of major adverse cardiovascular events in a patient with type 2 diabetes mellitus, comprising administering dulaglutide in a therapeutically effective amount to the patient once weekly, wherein the patient has type 2 diabetes mellitus and either:(a) multiple cardiovascular risk factors without established cardiovascular disease; or (b) established cardiovascular disease (claim 1). A method of reducing the risk of major adverse cardiovascular events in a patient with type 2 diabetes mellitus, comprising:(a) identifying a patient having type 2 diabetes mellitus and either: i) multiple cardiovascular risk factors without established cardiovascular disease; or ii) established cardiovascular disease; and (b) administering dulaglutide in a therapeutically effective amount to the patient once weekly (claim 2). A method of improving glycemic control and reducing the risk of first occurrence of a major adverse cardiovascular event in a patient with type 2 diabetes mellitus, comprising administering dulaglutide in a therapeutically effective amount to the patient once weekly, wherein the patient has type 2 diabetes mellitus and either:(a) multiple cardiovascular risk factors without established cardiovascular disease; or (b) established cardiovascular disease (claim 3), wherein the patient has multiple cardiovascular risk factors without established cardiovascular disease (claim 4), wherein the cardiovascular risk factors are selected from the group consisting of (a), (b), (c), (d) and (e):(a) tobacco use; (b) at least 1 of: I) use of at least 1 approved lipid modifying therapy to treat hypercholesterolemia; or ii) a documented untreated low-density lipoprotein cholesterol (LDL-C) >3.4 mmol/L (130 mg/dL) within the past 6 months; (c) at least 1of:i) high-density lipoprotein cholesterol (HDL-C)measurement within the past 6 months of: <1.0 mmol/L (40 mg/dL) for men; and <1.3 nmol/L (50mg/dL) for women; or ii) triglycerides >2.3 mmol/L (200 mg/dL) within the past 6 months; (d) at least 1 of: I) use of at least 1 blood pressure medication to treat hypertension; or ii) untreated systolic blood pressure (SBP) 2140 mm Hg or diastolic blood pressure (DBP) 295 mmHg; and (e) measured waist-to-hip ratio >1.0 for men and >0.8 for women (claim 5), wherein the patient has established cardiovascular disease (claim 6), wherein the method reduces the risk of a major adverse cardiovascular event by at least about 10% (claim 7), wherein the therapeutically effective amount of dulaglutide is selected from the group consisting of 1.5mg, 3.0 mg and 4.5mg (claims 8-9), wherein the once weekly administration of dulaglutide is continued for approximately 5 years (claim 10). The method further comprising administering to the patient one or more of the following: an angiotensin converting enzyme (ACE) ACE inhibitor; an angiotensin receptor blocker (ARB) ARB; a beta blocker; a calcium channel blocker; a diuretic; an antithrombotic agent; aspirin or a statin (claim 11) are taught by claims 1-8 of U.S. Patent No. 11,890,325.
Conclusion
No claim is allowed.
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/GYAN CHANDRA/Primary Examiner, Art Unit 1674
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