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 .
DETAILED ACTION
Applicant’s amendment and remarks, filed on September 15, 2025, in which claims 4-6 are amended, claims 1-3 are cancelled, and claims 9-16 are newly added, are acknowledged.
Claims 4-16 are pending and examined on the merits herein.
Priority
This application is a National Stage entry of PCT/EP2021/058005 filed on March 26, 2021 and claims priority to EPO foreign application 20166749.0 filed on March 30, 2020. A certified copy of the foreign priority document in English has been received.
Rejections Withdrawn
Applicant’s amendment and remarks, dated 9/15/2025, with respect to the rejection of claims 4-8, under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method for inhibiting or slowing the progression of diabetic nephropathy (DN), and wherein the inhibition or slowed progression of DN reduces kidney fibrosis, does not reasonably provide enablement for a method for preventing diabetic nephropathy (DN), or wherein the inhibition or slowed progression of DN prevents kidney fibrosis, has been carefully considered, and are persuasive. Claim 4 has been amended to particularly limit the subject to having diabetic nephropathy. Claims 5-8 depend from claim 4. This rejection is withdrawn.
The following are modified/new grounds of rejections to address applicant’s amendment to the claim limitations.
Claim Rejections - 35 USC § 103
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 (i.e., changing from AIA to pre-AIA ) 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 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 4-6 and 8-16 are rejected under 35 U.S.C. 103 as being unpatentable over Salatto et al. (IDS 9/28/2022), in view of WO 2014/001554 to Cravo (IDS 9/28/2022).
Salatto teaches that selective activation of AMPK b1-containing isoforms improves kidney function in a rat model of diabetic nephropathy. Patients who suffer from diabetic nephropathy (DN), a form of chronic kidney disease that is linked mechanistically to diabetes and metabolic syndrome, are in acute need of disease-modifying treatment options that will delay or prevent the progression to end stage renal disease (p. 303, Introduction, left column). The etiology of this disease progression is complex. Salatto selected the protein kinase, adenosine monophosphate-activated protein kinase (AMPK), as a potential therapeutic target since it met their two criteria for having 1) a concordance between genetic loci associated with disease, and 2) evidence of efficacy in preclinical models (p. 303, Introduction, right column). In their study, Salatto identified novel, specific, small molecule activators of AMPK that had potential for clinical development as a treatment option for DN (p. 304, left column, first incomplete paragraph). PF-06409577 and PF-249 were identified as selective activators of AMPK b1-containing heterotrimers, with minimal off-target pharmacology based on a broad panel of receptors, channels, phosphodiesterases, and kinases (p. 307, left column, Results, first paragraph).
In a ZSF1 rat model commonly used as a preclinical model of DN since it exhibits many characteristics of the human disease, it was shown that oral administration of PF-06409577, at doses of 10, 30, or 100 mg/kg every day, resulted in dose-dependent reductions in proteinuria in the obese ZSF1 animals, with greater than 2-fold reduction in 24-hour urinary albumin loss compared to control after 60 days of treatment (p. 308, left column). Salatto also evaluated the role of PF-06409577 in mTOR activity as AMPK is well-known to be a negative regulator of mTOR1, raising the possibility that this mechanism could be responsible for the improvements in renal function observed in obese ZSF1 rats treated with AMPK activators (p. 309, paragraph bridging columns 1 and 2). The phosphorylation state of ribosomal S6 kinase is a marker of mTOR activation that has been used histologically to evaluate glomerular mTOR signaling. Histologic assessment of obese ZSF1 kidneys revealed kidneys with increased p-S6 levels within the glomeruli, and treatment of ZSF1 obese animals with 100 mg/kg PF-06409577 reduced p-S6 within glomeruli to levels comparable to lean animals and significantly less than vehicle-treated obese ZSF1 rats. Based on their results, Salatto concluded that activators of AMPK warrant further testing as treatment of human DN.
The teachings of Salatto differ from that of the instantly claimed invention in that Salatto does not teach administering a compound of instant Formula (I) for treatment of DN.
Cravo ‘554 teaches thienopyridone derivatives useful as activators of AMPK. The compounds have the structure of formula (1) (p. 7, lines 1-21), and are disclosed as being direct AMPK activators useful for the treatment of diabetes, metabolic syndrome, obesity, liver disease, hepatic steatosis, liver fibrosis, retinopathies or neuropathies, among others, in a subject (p. 7, lines 23-30; p. 19, lines 21-31). The subject includes mammals, more particularly a human (p. 21, lines 25-26). It is taught that AMPK has a role in regulating the mTOR pathway, a kinase that is a key regulator of protein synthesis (p. 4, lines 16-21). AMPK inhibits mTOR action by phosphorylation on Thr-2446, thereby indirectly and directly inhibiting the activity of mTOR to limit protein synthesis. Preferred compounds of formula (1) are disclosed at p. 11, line 27 – p. 12, line 25. The compound of Example 12, 2-chloro-4-hydroxy-3-(5-hydroxytetralin-6-yl)-5-phenyl-7H-thieno[2,3-b]pyridine-6-one (p. 31-33) is identical to instant Formula (I). The compounds can be used in their final non-salt form, or can also be used in the form of pharmaceutically acceptable salts derived from various organic and inorganic acids and bases (p. 15, line 10 – p. 18, line 20). Cravo ‘554 teaches that pharmaceutically acceptable base-addition salts of the compounds are formed with metals or amines, such as alkali metals and alkaline earth metals or organic amines (p. 17, lines 24-29). Preferred metals are sodium, potassium, magnesium, and calcium. Pharmaceutical compositions can be administered in the form of dosage units, such as 0.5 mg to 1 g, preferably 1 mg to 700 mg, particularly preferably 5 mg to 100 mg of the compound (p. 22, lines 6-16). It is further taught that the dosage will depend on the disease condition being treated, the method of administration, and the age, weight and condition of the patient. The pharmaceutical compositions can be administered via any suitable method, including oral, vaginal, or parenteral (p. 22, lines 23-28). Compounds were tested in a diabetic animal model and showed the efficacy of compounds 12 and 19 in controlling glycemia (p. 36, lines 10-20).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the AMPK activators disclosed in the method of Salatto for treatment of DN, with the thienopyridone derivatives of Cravo ‘554, such as compound 12, with a reasonable expectation of success since Cravo ‘554 teaches that their disclosed thienopyridone derivatives are useful as direct activators of AMPK. As indicated in MPEP 2143(I), the simple substitution of one known element for another to obtain predictable results is prima facie obvious. One of ordinary skill in the art would further have a reasonable expectation of success since Cravo ‘554 teaches that the compounds are useful in treatment of conditions including diabetes and neuropathy, and Salatto teaches that there is a mechanistic link between DN and diabetes.
Regarding instant claims 9, 10, and 12-16, it is noted that the combined teachings of the prior art do not expressly teach that administration of the thienopyridone derivatives, such as compound 12 of Cravo ‘554, would result in an increase in the GFR of the subject, slows diabetic nephropathy and slows GFR decrease, reduces albuminuria, reduces urine gluclose levels, reduces urine volume, and slows the increase of urine volume. However, the indicated recitations are considered to be merely a mechanism of the action of the treatment. Applicant’s recitation of a new mechanism of action for the prior art method would not, by itself, does not distinguish the instant claims over the prior art teaching the same or nearly the same method steps. Since the combined teachings of the prior art suggest the same active method steps to the same or overlapping patient population, the recited effects would necessarily flow.
The data presented in the instant Specification has been considered but is not found to provide a showing of unexpected results to obviate the prima facie case set forth above.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Salatto et al. (IDS 9/28/2022), in view of WO 2014/001554 to Cravo (IDS 9/28/2022), as applied to claim 4, further in view of WO 2020/099678 to Bolze (PTO-892 5/15/2025).
The combined teachings of Salatto and Cravo ‘554 are as discussed above.
The combined teachings of Salatto and Cravo ‘554 differ from that of instant claim 7 in that although the combined teachings of Salatto and Cravo ‘554 teach pharmaceutically acceptable salts, including a potassium salt, of their disclosed thienopyridone derivatives, they do not teach a monohydrate potassium salt of the compound of formula (I).
Bolze ‘678 teaches a process for preparing a monohydrate potassium salt of a thienopyridone derivative. In particular, Bolze ‘678 teaches a process for preparing a monohydrate potassium salt of formula (I), and a pharmaceutical composition comprising the monohydrate potassium salt of formula (I) (p. 4, lines 6-10). The monohydrate potassium salt of formula (I) is also taught for use as a medicament, in particular for use in the treatment of diabetes, metabolic syndrome, liver fibrosis, retinopathies, neuropathies, amongst others (p. 4, line 11 – p. 5, line 2). Bolze ‘678 teaches that WO 2014/001554 discloses thienopyridone derivatives that are known to be AMPK activators, as well as a compound of formula (II) (p. 2, lines 1-14). The compound of formula (II) of Bolze ‘678, which is disclosed in WO 2014/001554, corresponds to the compound of instant Formula (I). Bolze ‘678 teaches that a corresponding potassium salt of the compound of formula (II) has great potential due to its pharmacological and physical properties, but when prepared according to the method of WO 2014/001554, the obtained compound is amorphous (p. 4, lines 15-17). Bolze ‘678 teaches that preparation of the monohydrate form of formula (I), yielding the monohydrate potassium salt of formula (I), yields a compound that is in a more stable form, and can be prepared using green reagents and milder conditions (p. 3, lines 10-19).
Thus, one of ordinary skill in the art would have been motivated to substitute compound 12, or the potassium salt of compound 12, in the method for treating DN, as disclosed in the combined teachings of Salatto and Cravo ‘554, before the effective filing date of the claimed invention, with the monohydrate potassium salt of formula (I), as disclosed in Bolze ‘678, to arrive at the instantly claimed invention because Bolze ‘678 teaches that the monohydrate potassium salt of formula (I) yields a compound that is in a more stable form, and can be prepared using green reagents and milder conditions. One of ordinary skill in the art would have a reasonable expectation of success because both the monohydrate potassium salt of formula (I) as disclosed by Bolze ’678, and compound 12, or the potassium salt form thereof, as disclosed in the combined teachings of the prior art, are the same compound that merely differ in their salt/hydrate form, and are each taught to be useful as AMPK activators. The data presented in the instant Specification has been considered but is not found to provide a showing of unexpected results to obviate the prima facie case set forth above.
Response to Arguments
Applicant’s arguments, dated 9/15/2025, with respect to the rejection of claims 4-6 and 8 as being rejected under 35 U.S.C. 103 as being obvious over Salatto, in view of WO 2014/001554 to Cravo, have been carefully considered, but are not persuasive.
Applicant argues that Salatto discloses two tested compounds described as AMPK b1 activators, but that these compounds are indole derivatives that are structurally very different from the compound of Formula (I) of the instant invention. Applicant additionally argues that Salatto is totally silent about other possible AMPK activators for use in their disclosed method, particularly directing those skilled in the art to small molecule activators of AMPK that target the b1 subunit of AMPK. Applicant further argues that Salatto does not provide any teaching, suggestion, or direction to the compound, a pharmaceutical salt and/or solvate, recited in the instant claims.
Applicant’s arguments have been carefully considered, but are not persuasive. Although Salatto only discloses two compounds that are structurally very different from that of the instant claims, and Salatto teaches that the two compounds are b1 activators, both the compounds of Salatto, and those of Cravo ‘554, are taught to have the same activity, particularly, as AMPK activators. Thus, the teachings of Cravo ‘554 are sufficient to cure the deficiencies of Salatto by substituting one known AMPK activator with another.
Applicant submits that one skilled in the art would not have a reasonable expectation of success in substituting the compounds of Salatto with compound 12 of Cravo to arrive at the presently claimed invention based on the mere fact that Cravo teaches that compound 12 is an AMPK activator. Applicant points to Salatto as admitting that the etiology of DN progression is quite complex, and that Salatto fails to provide any clear and robust evidence showing that the efficacy of the tested compound on DN relies on AMPK activation only. Applicant further argues that AMPK does not refer to one single protein, but to a plurality of isoforms, citing to Steinberg for support. Thus, applicant submits that because the teachings of Salatto direct one to inhibitors that target the b1 subunit of AMPK, one skilled in the art would have been directed to inhibitors known to target that subunit of AMPK.
Applicant’s arguments have been carefully considered, but are not found persuasive. While Salatto provides reasons for why they selected their particularly disclosed AMPK activators, which happen to target the b1 subunit, Salatto specifically teaches that multiple interventional studies in rodent models of diabetic kidney disease have suggested the potential benefits of activating AMPK for DN (p. 304, left column, first incomplete paragraph), thereby suggesting that compounds which activate AMPK in general can be considered for the treatment of DN. Since Cravo ‘554 teaches that their compounds are useful as activators of AMPK, and useful for the treatment of diabetes, metabolic syndrome, and retinopathies or neuropathies, one of ordinary skill in the art would have a reasonable expectation of success in substituting the compounds of Salatto with those of Cravo ‘554. Furthermore, one of orindary skill in the art would have a reasonable expectation of success as Salatto teaches that their disclosed compound lowers glomerular mTOR signaling by inhibiting mTORC1 (p. 309), similar to the teachings of Cravo ‘554 that their disclosed compounds inhibit mTOR (p. 4).
While Salatto does point out that the etiology of DN progression is quite complex, as discussed above, Salatto specifically teaches that AMPK activators have been pursued as targets for treatment of DN. Regarding applicant’s argument that Salatto fails to provide any clear and robust evidence showing the efficacy of the tested compound on DN relies on AMPK activation only, applicant is requested to note that obviousness does not require absolute predictability, however, at least some degree of predictability is required. See MPEP § 2143.02(II). Towards this end, similar to the compounds of Salatto, the compounds of Cravo ‘554 are taught to be AMPK activators useful in the treatment of diseases directed to diabetes and retinopathies (kidney disease), and furthermore, both references teach that their compounds inhibit mTOR, which Salatto teaches results in lowering glomerular signaling.
Applicant also argues that the fact that a claimed species or subgenus is encompassed by a prior art genus is not sufficient by itself to establish a prima facie case of obviousness. Thus, applicant argues that there is nothing in the teachings of the cited references that would have directed one to compound 12 in Cravo. Applicant’s argument has been carefully considered but is not persuasive. Salatto specifically suggests that AMPK activators are useful in the treatment of DN. Cravo ‘554 specifically disclose their compounds as being AMPK activators. Thus, absent any evidence of unexpected results, it would have been prima facie obvious for one of ordinary skill in the art to substitute one known AMPK activator with another, with a reasonable expectation that it would be useful in the treatment of DN.
Applicant argues that a prima facie case of obviousness can be rebutted by showing that the claimed invention exhibits one or more superior properties or advantages that a person of ordinary skill in the art would have found surprising or unexpected. Specifically, applicant argues that the instant application demonstrated that the claimed compound significantly improves the clinical signs of diabetic nephropathy, such as GFR impairment, glycosuria, and increase in urinary volume, and that therapeutic effects are visible after 8 days of treatment only, which results would not have been expected in view of the teachings of Salatto and Cravo. Applicant further argues that the compound of Formula (I) was tested in a pre-clinical model of type-2 diabetes-related renal dysfunction, namely obese ZSF1, also showing improvements in renal function after only 8 days of treatment. Applicant’s argument, and the data of the instant specification, have been carefully considered, but are not persuasive to show unexpected results over the prior art.
The data in Figures 1-4 of the instant Specification compare untreated ZSF-1 mice with PXL770-treated ZSF-1 mice. While this data does show that PXL770-treated ZSF-1 mice exhibited improvement over untreated mice at 90 days, arguments of unexpected results must compare the claimed invention with the closest prior art in order to show non-obviousness over the prior art. See MPEP 716.02(e), part I. Therefore, a proper showing of unexpected results must compare PXL770-ZSF-1 treated mice against the same mice treated with the compounds disclosed by Salatto. There is no evidence provided to support that the AMPK activators of Cravo ‘554 would behave differently from Salatto, particularly since Salatto also teaches their compounds to be AMPK activators. Furthermore, Cravo ‘554 teaches that their disclosed AMPK activators can be used to treat diabetes and nephropathy. Such there is significant patient overlap with diabetic nephropathy.
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 4-6 and 8-16 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 8, and 10 of U.S. Patent No. 9,284,329, in view of WO 2014/001554 to Cravo (IDS 9/28/2022) and Salatto et al. (IDS 9/28/2022).
Claim 1 of ‘329 is drawn to a compound of formula (I), wherein claim 8 further limits the structures to various species, including 2-chloro-4-hydroxy-3-(5-hydroxytetralin-6-yl)-5-phenyl-7H-thieno[2,3-b]pyridine-6-one. Claim 10 of ‘329 is drawn to a method of treating diabetes, metabolic syndrome, liver disease, retinopathies or neuropathies, among other diseases, comprising administering an effective amount of the compound of claim 1. The indicated compound recited in claim 8 of ‘329 is the same as that recited in instant claim 4.
The claims of ‘329 differ from the instant claims in that ‘329 does not claim a method of treating diabetic nephropathy.
The independent teachings of Cravo ‘554 and Salatto are as discussed above.
It would have been prima facie obvious for one of ordinary skill in the art to use 2-chloro-4-hydroxy-3-(5-hydroxytetralin-6-yl)-5-phenyl-7H-thieno[2,3-b]pyridine-6-one as recited in ‘329 for treatment of DN with a reasonable expectation of success because Cravo ‘554 teaches the thienopyridone derivative of ‘329 as being a direct AMPK activator, and Salatto teaches that AMPK activators are useful in the treatment of DN.
With regards to instant claim 5, it would have been prima facie obvious for one of ordinary skill in the art to administer the compound/composition to a human as Cravo ‘554 teaches administration of thienopyridone derivatives to a subject, including a human. It would have been prima facie obvious for one of ordinary skill in the art to optimize the dosage as Cravo ‘554 provides dosages for administration of thienopyridone derivatives, and further teaches that the dosage will depend on the disease condition being treated, the method of administration, and the age, weight and condition of the patient.
With regards to instant claim 6, one of ordinary skill in the art would reasonably expect administration of the compound to reduce proteinuria as Salatto teaches that administration of PF-06409577, an AMPK activator, resulted in dose-dependent reductions in proteinuria in the obese ZSF1 animals.
With regards to instant claim 8, it would have been prima facie obvious for one of ordinary skill in the art to administer the compound via the oral route as Cravo ‘554 teaches that the compounds can be administered via any suitable method, including oral, vaginal, or parenteral.
Regarding instant claims 9, 10, and 12-16, these recitations are considered to be merely a mechanism of the action of the treatment. Applicant’s recitation of a new mechanism of action for the prior art method would not, by itself, does not distinguish the instant claims over the prior art teaching the same or nearly the same method steps. Since the combined teachings suggest the same active method steps to the same or overlapping patient population, the recited effects would necessarily flow.
Claim 7 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 8, and 10 of U.S. Patent No. 9,284,329, in view of WO 2014/001554 to Cravo (IDS 9/28/2022), Salatto et al. (IDS 9/28/2022), and WO 2020/099678 to Bolze (PTO-892, 5/15/2025).
Claim 1 of ‘329 is drawn to a compound of formula (I), wherein claim 8 further limits the structures to various species, including 2-chloro-4-hydroxy-3-(5-hydroxytetralin-6-yl)-5-phenyl-7H-thieno[2,3-b]pyridine-6-one. Claim 10 of ‘329 is drawn to a method of treating diabetes, metabolic syndrome, liver disease, retinopathies or neuropathies, among other diseases, comprising administering an effective amount of the compound of claim 1.
The indicated compound recited in claim 8 of ‘329 is the same compound of instant claim 4, but differs from that recited in instant claim 7 with respect to the monohydrate potassium salt form as required in instant claim 7, whereas claim 8 of ‘329 does not recite any salt form. The claims of ‘329 also differ from the instant claim in that it does not claim a method of treating diabetic nephropathy.
The independent teachings of Cravo ‘554, Salatto, and Bolze ‘678 are as discussed above.
It would have been prima facie obvious for one of ordinary skill in the art to use 2-chloro-4-hydroxy-3-(5-hydroxytetralin-6-yl)-5-phenyl-7H-thieno[2,3-b]pyridine-6-one as recited in ‘329 for treatment of DN with a reasonable expectation of success because Cravo ‘554 teaches the thienopyridone derivative of ‘329 as being a direct AMPK activator, and Salatto teaches that AMPK activators are useful in the treatment of DN. One of ordinary skill in the art would have also been motivated to use the monohydrate potassium salt form of the compound recited in ‘329 because Bolze ‘678 teaches that the monohydrate potassium salt of formula (I) is in a more stable form that the potassium salt form, and can be prepared using green reagents and milder conditions.
Claims 4-16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 11,850,238, in view of WO 2014/001554 to Cravo (IDS 9/28/2022) and Salatto et al. (IDS 9/28/2022).
The claims of ‘238 are drawn to a method of treating adrenoleukodystrophy and/or adrenomyeloneuropathy comprising administering a compound, or a pharmaceutically acceptable salt or solvate thereof, as recited in claims 1 and 9. The first structure of claim 1 of ‘238 is the same as that of Formula (I) recited in instant claim 4. Claim 2 limits the compound to the monohydrate potassium salt of Formula (Ia). Claim 3 limits the dosage to 0.5-3000 mg daily. Claim 7 limits the method to oral administration. Claim 10 limits the dosage to 20-1000 mg daily.
The claims of ‘238 differ from that of the instant claims in that it is drawn to the treatment of adrenoleukodystrophy and/or adrenomyeloneuropathy instead of the instantly claimed DN.
The independent teachings of Cravo ‘554 and Salatto are as disclosed above.
It would have been prima facie obvious to apply the method of administering the compound of formula (I), or formula (Ia) as recited in ‘238 for treating adrenoleukodystrophy and/or adrenomyeloneuropathy to the treatment of DN with a reasonable expectation of success because Cravo ‘554 teaches that the thienopyridone compounds of ‘238 are recognized AMPK activators, and Salatto teaches that AMPK activators are useful in the treatment of DN.
With regards to instant claim 5, it would have been prima facie obvious for one of ordinary skill in the art to administer the compound/composition to a human as Cravo ‘554 teaches administration of thienopyridone derivatives to a subject, including a human.
With regards to instant claim 6, one of ordinary skill in the art would reasonably expect administration of the compound to reduce proteinuria as Salatto teaches that administration of PF-06409577, an AMPK activator, resulted in dose-dependent reductions in proteinuria in the obese ZSF1 animals.
Regarding instant claims 9, 10, and 12-16, these recitations are considered to be merely a mechanism of the action of the treatment. Applicant’s recitation of a new mechanism of action for the prior art method would not, by itself, does not distinguish the instant claims over the prior art teaching the same or nearly the same method steps. Since the combined teachings suggest the same active method steps to the same or overlapping patient population, the recited effects would necessarily flow.
Claims 4-16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 15 and 16 of U.S. Patent No. 12,319,700 (previously claims 29 and 30 of copending Application No. 17/293,977), in view of WO 2014/001554 to Cravo (IDS 9/28/2022) and Salatto et al. (IDS 9/28/2022).
The claims of ‘700 are drawn to a process for preparing a monohydrate potassium salt of formula (I). The monohydrate salt of formula (I) has the same structure as the thienopyridone derivative of Formula (I) recited in instant claim 4, and is the same monohydrate potassium salt compound recited in instant claim 7.
The claims of ‘700 differ from the instant claims in that it does not claim a method of treating diabetic nephropathy using the monohydrate potassium salt of formula (I).
The independent teachings of Cravo ‘554 and Salatto are as discussed above.
It would have been prima facie obvious for one of ordinary skill in the art to use the prepared monohydrate potassium salt of formula (I) in ‘700 for treatment of DN with a reasonable expectation of success because Cravo ‘554 teaches the thienopyridone derivative of application ‘700 as being a direct AMPK activator, and Salatto teaches that AMPK activators are useful in the treatment of DN.
With regards to instant claim 5, it would have been prima facie obvious for one of ordinary skill in the art to administer the compound/composition to a human as Cravo ‘554 teaches administration of thienopyridone derivatives to a subject, including a human. It would have been prima facie obvious for one of ordinary skill in the art to optimize the dosage as Cravo ‘554 provides dosages for administration of thienopyridone derivatives, and further teaches that the dosage will depend on the disease condition being treated, the method of administration, and the age, weight and condition of the patient.
With regards to instant claim 6, one of ordinary skill in the art would reasonably expect administration of the compound to reduce proteinuria as Salatto teaches that administration of PF-06409577, an AMPK activator, resulted in dose-dependent reductions in proteinuria in the obese ZSF1 animals.
With regards to instant claim 8, it would have been prima facie obvious for one of ordinary skill in the art to administer the compound via the oral route as Cravo ‘554 teaches that the compounds can be administered via any suitable method, including oral, vaginal, or parenteral.
Regarding instant claims 9, 10, and 12-16, these recitations are considered to be merely a mechanism of the action of the treatment. Applicant’s recitation of a new mechanism of action for the prior art method would not, by itself, does not distinguish the instant claims over the prior art teaching the same or nearly the same method steps. Since the combined teachings suggest the same active method steps to the same or overlapping patient population, the recited effects would necessarily flow.
Claims 4-16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 12,310,949 (previously claims 19, 20, 24, 30, 32, and 33 of copending Application No. 17/915,123), in view of WO 2014/001554 to Cravo (IDS 9/28/2022) and Salatto et al. (IDS 9/28/2022).
The claims of ‘949 are drawn to a method of limiting renal cyst growth or reducing renal cyst volume in a subject having autosomal dominant polycystic kidney disease (ADPKD) comprising administering to the subject a compound of formula (II), or pharmaceutically acceptable salt or solvate thereof. Claim 20 limits the administered daily dosage to 0.5-3000 mg, 20-1000 mg, or 60-500 mg. Claim 24 limits the method to the monohydrate potassium salt of formula (Ia). Claim 5 limits the method to oral administration.
The claims of ‘949 differ from that of the instant claims in that it is drawn to the treatment of autosomal dominant polycystic kidney disease instead of the instantly claimed DN.
The independent teachings of Cravo ‘554 and Salatto are as disclosed above.
It would have been prima facie obvious to apply the method of administering the compound of formula (II), or formula (Ia) as recited in ‘949 for treating ADPKD to the treatment of DN with a reasonable expectation of success because Cravo ‘554 teaches that the thienopyridone compounds of ‘949 are recognized AMPK activators, and Salatto teaches that AMPK activators are useful in the treatment of DN.
With regards to instant claim 5, it would have been prima facie obvious for one of ordinary skill in the art to administer the compound/composition to a human as Cravo ‘554 teaches administration of thienopyridone derivatives to a subject, including a human.
With regards to instant claim 6, one of ordinary skill in the art would reasonably expect administration of the compound to reduce proteinuria as Salatto teaches that administration of PF-06409577, an AMPK activator, resulted in dose-dependent reductions in proteinuria in the obese ZSF1 animals.
Regarding instant claims 9, 10, and 12-16, these recitations are considered to be merely a mechanism of the action of the treatment. Applicant’s recitation of a new mechanism of action for the prior art method would not, by itself, does not distinguish the instant claims over the prior art teaching the same or nearly the same method steps. Since the combined teachings suggest the same active method steps to the same or overlapping patient population, the recited effects would necessarily flow.
Response to Arguments
Applicant’s arguments, filed on 9/15/2025, with respect to the rejection of the claims 4-6 and 8 under the judicially created doctrine of “obviousness-type” double-patenting over claims 1, 8, and 10 of U.S. Patent No. 9,284,329, in view of Cravo and Salatto, and the rejection of claim 7, further in view of Bolze, have been carefully considered, but are not persuasive. Applicant’s arguments are the same as set forth above over the prior art rejections. Thus, the response to applicant’s arguments is the same as that set forth above.
Applicant’s arguments, filed on 9/15/2025, with respect to the rejection of the claims 4-8 under the judicially created doctrine of “obviousness-type” double-patenting over claims 1-19 of U.S. Patent No. 11,850,238, in view of Cravo and Salatto, have been carefully considered, but are not persuasive. Applicant argues that the claims of the present application would not extend the protection of the same invention claimed within the ‘238 patent, nor is there any evidence of record that establishes that the claimed invention is an obvious variation of the invention claimed in the ‘238 patent. Applicant’s argument has been carefully considered, but is not found persuasive. The variation is the application of the recited compounds being recognized as AMPK activators, said AMPK activators being involved in a different disease. Since the compound used in the method of ‘238 is a recognized AMPK activator, it would have been prima facie obvious for one of ordinary skill in the art to apply it in the treatment of other diseases in which AMPK activation is found to be beneficial.
Applicant’s arguments, filed on 9/15/2025, with respect to the rejection of the claims 4-8 under the judicially created doctrine of “obviousness-type” double-patenting over claims 29 and 30 co-pending application 17/293,977 (now claims 15 and 16 of U.S. Patent No. 12,319,700), in view of Cravo and Salatto, have been carefully considered, but are not persuasive. Applicant’s arguments are the same as set forth above over the prior art rejections. Thus, the response to applicant’s arguments is the same as that set forth above.
Applicant’s arguments, filed on 9/15/2025, with respect to the rejection of the claims 4-8 under the judicially created doctrine of “obviousness-type” double-patenting over claims 19, 20, 24, 30, 32, and 33 of co-pending application 17/915,123 (now claims 1-6 of U.S. Patent No. 12,310,949), in view of Cravo and Salatto, have been carefully considered, but are not persuasive. Applicant argues that the claims of the present application would not extend the protection of the same invention claimed within the ‘949 patent, nor is there any evidence of record that establishes that the claimed invention is an obvious variation of the invention claimed in the ‘949 patent. In particular, applicant argues that the claims of the ‘949 patent are drawn to limiting renal cyst growth or reducing renal cyst volume in a subject having autosomal dominant polycystic kidney disease using a compound of Formula (I), and that there is no reason to alter the method recited in the claims of the ‘949 patent in order to treat DN. The variation is the application of the recited compounds being recognized as AMPK activators, said AMPK activators being involved in a different disease. Since the compound used in the method of ‘949 is a recognized AMPK activator, it would have been prima facie obvious for one of ordinary skill in the art to apply it in the treatment of other diseases in which AMPK activation is found to be beneficial.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a). A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/SCARLETT Y. GOON/
Supervisory Patent Examiner
Art Unit 1693