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 .
Status of the Claims
Claims 1-18 are pending in the application. Claims 1-18 are examined herein.
Priority
This application is a CON of 18/351,587 filed 07/13/2023 PAT 12030861.
The subject matter of the instant claims are supported by the parent 18/351,587 application. Accordingly the effective filing date of instant claims 1-18 is 07/13/2023.
Information Disclosure Statement
The information disclosure statements submitted 02/06/2025 and 07/03/2024 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 6-7 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Regarding claim 6, the claim depends from claim 2 which recites “The L-lysine salt of 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid is in a crystalline form”. However, claim 6 recites the limitation “optionally triggering the formation of a crystalline form”, which does not require the compound to be in a crystalline form. This broadens the scope of the dependent claim 6, which is improper.
Claim 7 depends from claim 6 and is therefore, similarly rejected.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
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 1, 8-15 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Vonderscher et al. (US 2022/0249469 A1, publication date 11 August 2022 and PCT filing date 17 July 2020, hereinafter Vonderscher, in the IDS) in view of Abou-Taleb et al. (Exploration of the Safety and Solubilization, Dissolution, Analgesic Effects of Common Basic Excipients on the NSAID Drug Ketoprofen, 20 February 2023, hereinafter Abou-Taleb, in the IDS).
Regarding instant claim 1, Vonderscher teaches EYP001 (i.e., 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid, as evidenced by lines 19-21 of instant specification) and indicates EYP001 refers to the compound and any pharmaceutically acceptable salt thereof (Paras. [0016]-[0017]).
Vonderscher does not teach an L-lysine salt of EYP001 (i.e., 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid).
Abou-Taleb teaches numerous solubilization techniques to improve the solubility and dissolution rates of different water-insoluble drugs, including salt formation (Pg. 2, first paragraph). Abou-Taleb teaches successful use of amino acids in solubilizing both ionizable and non-ionizable drugs and a growing interest in utilizing amino acids due to their safety and tolerability (Pg. 2, second paragraph). Abou-Taleb teaches the L-lysine salt of a small molecule (ketoprofen, a weakly acidic drug) having a carboxylic acid functional group to have enhanced solubility and improved dissolution rates (Pg. 2, third paragraph; Pg. 5, second full paragraph; Pg. 13, last paragraph). Abou-Taleb further the ketoprofen lysine salt demonstrated more rapid and complete absorption than the acid form, attaining peak plasma concentrations faster (Pg. 10, second paragraph).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, in view of the teachings of Vonderscher and Abou-Taleb, to have prepared the L-lysine salt to arrive at the claimed L-lysine salt of EYP001 (i.e., 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid) with a reasonable expectation of success in enhancing the solubility and dissolution characteristics of EYP001 (EYP001 is inherently known to have low water solubility). Vonderscher teaches EYP001 (i.e., 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid) and any pharmaceutically acceptable salt thereof. Abou-Taleb teaches numerous solubilization techniques to improve the solubility and dissolution rates of different water-insoluble drugs, including salt formation. Abou-Taleb teaches successful use of amino acids in solubilizing both ionizable and non-ionizable drugs. Abou-Taleb teaches the L-lysine salt of a small molecule (ketoprofen, a weakly acidic drug) having a carboxylic acid functional group to have enhanced solubility and improved dissolution rates. Abou-Taleb teaches the ketoprofen lysine salt demonstrated more rapid and complete absorption than the acid form, attaining peak plasma concentrations faster. Therefore, one of ordinary skill in the art would be motivated to prepare an L-lysine salt of EYP001 (i.e., 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid). The motivation being to improve the biopharmaceutical properties of EYP001, a weakly acidic drug (Abou-Taleb, Pg. 2, fifth paragraph; Pg. 10, second paragraph).
Regarding instant claims 8-10, the combined teachings of Vonderscher and Abou-Taleb render obvious an L-lysine salt of EYP001 (i.e., 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid). Vonderscher further teaches pharmaceutical compositions of EYP001 combined with pharmaceutically acceptable excipients (Para. [0036]). Vonderscher further teaches EYP001 can be used in combination with an additional active ingredient, wherein the additional active ingredient is a TLR7, TLR8 or TLR9 agonist, a RIG-I modulator, a STING agonist, an interferon , preferably IFN-α or a pegylated form thereof (Para. [0011]; Paras. [0060]-[0061]; Para. [0063]).
According to MPEP 2144.05(II)(A), "It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions."). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416, 82 USPQ2d 1385, 1395 (2007).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, in view of the teachings of Vonderscher and Abou-Taleb to have formulated a pharmaceutical composition of the L-lysine salt of EYP001 (i.e., 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid) or a combination composition with an additional therapeutic agent and a pharmaceutically acceptable excipient, as instantly claimed. Doing so would have been well within the skill of one of ordinary skill in the pharmaceutical arts, through routine experimentation.
Regarding instant claims 11-15 and 17, the combined teachings of Vonderscher and Abou-Taleb render obvious an L-lysine salt of EYP001 (i.e., 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid). Vonderscher teaches a method for treating a disease in a subject suffering from a disease, comprising administering a therapeutically effective amount of EYP001 (i.e., 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid) (Para. [0009]). Vonderscher teaches EYP001 (i.e., 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid) is intended to refer to the compound and any pharmaceutically acceptable salt thereof (Para. [0017]). Vonderscher teaches the disease is selected from the group consisting of chronic liver disease, gastrointestinal disease, renal disease, cardiovascular disease, metabolic disease and infection disease (Para. [0010]) (this reads on the limitations of instant claim 11). Vonderscher teaches the treatment results in reduced adverse effects (Para. [0029]; Para. [0007]).
Vonderscher teaches wherein the disease is infection disease selected from the group consisting of HBV infection and chronic hepatitis B (Para. [0054]; Para. [0071]; Paras. [0078]-[0079]) (this reads on the limitations of instant claims 12 and 13).
Vonderscher teaches the disease is a renal disease selected from the group consisting of diabetic nephropathy, focal segmental glomerulo sclerosis (FSGS) , hypertensive nephrosclerosis, chronic glomerulonephritis, chronic transplant glomerulopathy, chronic interstitial nephritis, and polycystic kidney disease (Para. [0051]). Vonderscher teaches the disease is Type I Diabetes; Type II Diabetes; clinical complications of Type I and Type II Diabetes selected from the group consisting of diabetic nephropathy (Para. [0047]) (this reads on the limitations of instant claim 15).
Vonderscher teaches wherein the disease is a chronic liver disease selected from the group consisting of primary biliary cholangitis (PBC), cerebrotendinous xanthomatosis (CTX), primary sclerosing cholangitis (PSC), drug induced cholestasis, intrahepatic cholestasis of pregnancy, parenteral nutrition associated cholestasis (PNAC) , bacterial overgrowth or sepsis associated cholestasis, autoimmune hepatitis, chronic viral hepatitis, alcoholic liver disease, nonalcoholic fatty liver disease (NAFLD) , nonalcoholic steatohepatitis (NASH) , alcoholic hepatitis, liver transplant associated graft versus host disease, living donor transplant liver regeneration, congenital hepatic fibrosis, choledocholithiasis, granulomatous liver disease, intra or extrahepatic malignancy, Sjogren's syndrome, Alagille syndrome, Sarcoidosis, Wilson's disease, Gaucher's disease, hemochromatosis, biliary atresia, ductopenic liver transplant rejection, cystic fibrosis liver disease and alpha 1-antitrypsin deficiency (Para. [0050]) (this reads on the limitations of instant claim 17).
Vonderscher teaches EYP001 can be used in combination with an additional active ingredient, wherein the additional active ingredient is a TLR7, TLR8 or TLR9 agonist, a RIG-I modulator, a STING agonist, an interferon, preferably IFN-α or a pegylated form thereof (Para. [0011]; Paras. [0060]-[0061]; Para. [0063]) (this reads on the limitations of instant claim 14).
According to MPEP 2144.05(II)(A), "It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions."). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416, 82 USPQ2d 1385, 1395 (2007).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, in view of the teachings of Vonderscher and Abou-Taleb to have arrived at the claimed method of treating a disease (as listed in instant claims 12-15 and 17), comprising administering an L-lysine salt of EYP001 (i.e., 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid) OR a combination composition with an additional active ingredient, such as, TLR7, TLR8 or TLR9 agonist, a RIG-I modulator, a STING agonist, an interferon, preferably IFN-α or a pegylated form thereof disease (as listed in instant claim 14), with a reasonable expectation of success in treating such conditions. The combination of Vonderscher and Abou-Taleb render obvious a method for treating a disease in a subject suffering from a disease, comprising administering a L-lysine salt of EYP001 (i.e., 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid). Vonderscher teaches treating various diseases (as listed in instant claims 12-13, 15 and 17), comprising administering a therapeutically effective amount of EYP001 (i.e., 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid) or a combination thereof (as listed in instant claim 14). Vonderscher teaches EYP001 (i.e., 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid) is intended to refer to this compound and any pharmaceutically acceptable salt thereof. Vonderscher teaches the treatment results in reduced adverse effects.
Therefore, one of ordinary skill in the art would be motivated to develop a method of treating the various diseases (as listed in instant claims 12-13, 15 and 17), comprising administering a therapeutically effective amount of L-lysine salt of EYP001 (i.e., 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid) or a combination thereof (as listed in instant claim 14). The motivation being to inhibit or decrease the adverse effects of FXR agonists (i.e., pruritus) while retaining therapeutic benefits of FXR agonists (Vonderscher, Para. [0007]).
Claims 16 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Vonderscher et al. (US 2022/0249469 A1, publication date 11 August 2022 and PCT filing date 17 July 2020, hereinafter Vonderscher, in the IDS) in view of Abou-Taleb et al. (Exploration of the Safety and Solubilization, Dissolution, Analgesic Effects of Common Basic Excipients on the NSAID Drug Ketoprofen, 20 February 2023, hereinafter Abou-Taleb, in the IDS) as applied to claims 1, 8-15 and 17 above, and further in view of Brees et al. (US 2022/0265619 A1, publication date 25 August 2022, hereinafter Brees, in the IDS).
The teachings of Vonderscher and Abou-Taleb are set forth in the obviousness rejection above and incorporated herein by reference.
Regarding instant claims 16 and 18, the combined teachings of Vonderscher and Abou-Taleb render obvious an L-lysine salt of EYP001 (i.e., 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid). Vonderscher and Abou-Taleb do not teach wherein said compound or composition is administered in combination with an ERA, an ACE inhibitor, an ARB, a RASS antagonist, a beta-blocker, a diuretic agent, a MRA, a SGLT2 inhibitor, a GLP 1 agonist or a combination thereof (as in instant claim 16) OR wherein said compound or composition is administered in combination with a SGLT2 inhibitor, a GLP1 agonist, a SGLT1 inhibitor, FGF 19, FGF21, a DPP-4 inhibitor, a PPAR agonist, a THR beta agonist, a FASN, an inhibitor of HSD17b13 or a combination thereof (as in instant claim 18).
Brees teaches a method for the treatment of a condition mediated by farnesoid X receptors (FXR), in particular liver diseases or intestinal diseases, e.g. NASH comprising administering to a subject in need thereof a pharmaceutical combination comprising : an FXR agonist and an SGLT inhibitor, e.g. SGLT 1/2 inhibitor (Paras. [0027]-[0029]; Claim 15; Claim 1). Brees teaches wherein the FXR agonist can be PXL007 (Para. [0036]; Para. [0134]; Claim 1) (i.e., EYP001 or 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid, as evidenced by lines 19-21 of the instant specification). Brees teaches the doses for this study were selected based on the expectation of achieving increased efficacy with the combination therapy, compared to individual monotherapies, while maintaining tolerability and safety of the patients (Para. [0227]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, in view of the teachings of Vonderscher, Abou-Taleb and Brees to have arrived at the claimed method of treating a disease, such as a liver disease or gastrointestinal disease comprising administering an L-lysine salt of EYP001 (i.e., 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid) in combination with a SGLT2 inhibitor with a reasonable expectation of success in treating such conditions. The combined teachings of Vonderscher and Abou-Taleb render obvious a method for treating a disease in a subject suffering from a disease, comprising administering a L-lysine salt of EYP001 (i.e., 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid). Brees teaches a method for the treatment of a condition mediated by farnesoid X receptors (FXR), in particular liver diseases or intestinal diseases, e.g. NASH comprising administering to a subject in need thereof a pharmaceutical combination comprising : an FXR agonist and an SGLT inhibitor, e.g. SGLT 1/2 inhibitor. Brees further teaches wherein the FXR agonist can be PXL007 (i.e., EYP001 or 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid). Brees teaches the doses for this study were selected based on the expectation of achieving increased efficacy with the combination therapy, compared to individual monotherapies, while maintaining tolerability and safety of the patients.
Therefore, one of ordinary skill in the art would be motivated to develop a method of treating a disease, such as a liver disease or gastrointestinal disease comprising administering an L-lysine salt of EYP001 (i.e., 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid) in combination with a SGLT2 inhibitor (as claimed in claims 16 and 18). The motivation being to achieve increased efficacy with the combination therapy, compared to individual monotherapies, while maintaining tolerability and safety of the patients (Brees, Para. [0227]).
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Vonderscher et al. (US 2022/0249469 A1, publication date 11 August 2022 and PCT filing date 17 July 2020, hereinafter Vonderscher, , in the IDS) in view of Abou-Taleb et al. (Exploration of the Safety and Solubilization, Dissolution, Analgesic Effects of Common Basic Excipients on the NSAID Drug Ketoprofen, 20 February 2023, hereinafter Abou-Taleb, in the IDS) as applied to claims 1, 8-15 and 17 above, and further in view of Variankaval et al. (From Form to Function: Crystallization of Active Pharmaceutical Ingredients, July 2008, hereinafter Variankaval, in the IDS).
The teachings of Vonderscher and Abou-Taleb are set forth in the obviousness rejection above and incorporated herein by reference.
Regarding instant claim 2, the combined teachings of Vonderscher and Abou-Taleb render obvious an L-lysine salt of EYP001 (i.e., 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid). Vonderscher and Abou-Taleb do not teach the L-lysine salt in a crystalline form.
Variankaval teaches crystallization represents a convenient and scalable
method to purify a drug substance (Pg. 1683, second column, second full paragraph). Variankaval teaches crystallinity confers various advantages during isolation, processing and storage of the drug, such as better impurity rejection, improved handling characteristics, such as sticking and flow and, in the majority of cases, better physical and chemical stability (Pg. 1682, second column, last paragraph).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, in view of the teachings of Vonderscher, Abou-Taleb and Variankaval to have crystallized the L-lysine salt of EYP001 (i.e., 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid) with a reasonable expectation of success in conferring better properties. The combined teachings of Vonderscher and Abou-Taleb render obvious an L-lysine salt of EYP001 (i.e., 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid). Variankaval teaches crystallization represents a convenient and scalable method to purify a drug substance. Variankaval teaches crystallinity confers various advantages during isolation, processing and storage of the drug, such as better impurity rejection, improved handling characteristics, such as sticking and flow and, in the majority of cases, better physical and chemical stability.
Therefore, one of ordinary skill in the art would be motivated to crystallize the L-lysine salt of EYP001 (i.e., 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid). The motivation being to provide a drug product with impeccable physicochemical stability and adequate shelf-life (Variankaval, Pg. 1687, continued paragraph).
Claims 3-7 are objected to as being dependent on a rejected base claim.
Double Patenting - Statutory
A rejection based on double patenting of the "same invention" type finds its support in the language of 35 U.S.C. 101 which states that "whoever invents or discovers any new and useful process... may obtain a patent therefor..." (Emphasis added). Thus, the term "same invention," in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957).
A statutory type (35 U.S.C. 101) double patenting rejection can be overcome by canceling or amending the claims that are directed to the same invention so they are no longer coextensive in scope. The filing of a terminal disclaimer cannot overcome a double patenting rejection based upon 35 U.S.C. 101.
Claims 3-5 are rejected under 35 U.S.C. 101 as claiming the same invention as that of claims 1-3 of U.S. Patent No. 12,030,861 B1.
The instant claims and the claims of the reference ‘861 patent are drawn to an L-lysine salt of 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid in a crystalline form.
The instant claims are drawn to a
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and a crystalline form with the X-ray diffraction pattern as in instant claim 5.
The claims of the reference ‘861 patent are drawn to
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.
This is a statutory double patenting rejection since both sets of claims are drawn to a crystalline form of an L-lysine salt of 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid with identical X-ray diffraction patterns.
Claims 1-5, 8-15 and 17-18 are rejected under 35 U.S.C. 101 as claiming the same invention as that of claims 1, 3-6, 10-12, 13-17 and 20-21 of co-pending Application No 18/762,718.
The instant claims and the claims of the co-pending ‘718 application are drawn to an L-lysine salt of 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic.
The instant claims are drawn to an L-lysine salt of 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic, crystalline forms thereof, a pharmaceutical or veterinary composition comprising the L-lysine salt or a combination composition thereof and methods of treatment thereof.
The claims of the co-pending ‘718 application are drawn to an L-lysine salt of 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic, crystalline forms thereof, a pharmaceutical or veterinary composition comprising the L-lysine salt or a combination composition thereof and methods of treatment thereof.
Claims 1 and 3-6 of the co-pending ‘718 application are identical in scope to instant claims 1-5 drawn to an L-lysine salt of 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic and crystalline forms thereof. Claims 10-12 of the co-pending ‘718 application are identical in scope to instant claims 8-10 (although claim 12 of the ‘718 application does not recite “or a combination thereof”, the “comprising” transitional phrase in claim 10 from which it depends allows for a combination of the additional therapeutic agent, thereby rendering the scope to be same) drawn to a pharmaceutical or veterinary composition comprising the L-lysine salt. Claims 13-17 and 20-21 of the co-pending ‘718 application are identical in scope to instant claims 11-15 and 17-18 drawn to a method of treatment thereof.
This is a statutory double patenting rejection since both sets of claims are drawn to identical claim language overall.
Claims 1-5, 8-11, 13 and 17 are rejected under 35 U.S.C. 101 as claiming the same invention as that of claims 23, 25-28, 32-36 and 39 of co-pending Application No 19/501,222.
The instant claims and the claims of the co-pending ‘222 application are drawn to an L-lysine salt of 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic.
The instant claims are drawn to an L-lysine salt of 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic, crystalline forms thereof, a pharmaceutical or veterinary composition comprising the L-lysine salt or a combination composition thereof and methods of treatment thereof.
The claims of the co-pending ‘222 application are drawn to an L-lysine salt of 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic, crystalline forms thereof, a pharmaceutical or veterinary composition comprising the L-lysine salt or a combination composition thereof and methods of treatment thereof.
Claims 23 and 25-28 of the co-pending ‘222 application are identical in scope to instant claims 1-5 drawn to an L-lysine salt of 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic and crystalline forms thereof. Claims 32-34 of the co-pending ‘222 application are identical in scope to instant claims 8-10 drawn to a pharmaceutical or veterinary composition comprising the L-lysine salt. Claims 35-36 and 39 of the co-pending ‘222 application are identical in scope to instant claims 11, 13 and 17 drawn to a method of treatment thereof.
This is a statutory double patenting rejection since both sets of claims are drawn to identical claim language overall.
Double Patenting - Nonstatutory
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-2 and 6-18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-48 of U.S. Patent No. 12,030,861 B1.
Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are drawn to an L-lysine salt of 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid.
The instant claims are drawn to an L-lysine salt of 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid, which is in a crystalline form in an embodiment, a process of preparation of the same, a pharmaceutical or veterinary composition and methods of treatment thereof.
The claims of the reference ‘861 patent are drawn to an L-lysine salt of 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid in a crystalline form characterized by the recited X-ray diffraction pattern, a process of preparation of the same, a pharmaceutical or veterinary composition and methods of treatment thereof.
Claims 1-3 of the reference ‘861 patent (drawn to a specific species of crystalline form) anticipate instant claims 1-2 drawn to an L-lysine salt of 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid and a crystalline form thereof. Claims 4-5, 19-20 and 34-35 of the reference ‘861 patent anticipate instant claims 6-7 drawn to a process of preparation of an L-lysine salt of 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid in a crystalline form. Claims 6-8, 21-23 and 36-38 of the reference ‘861 patent anticipate instant claims 8-10 drawn to a pharmaceutical or veterinary composition thereof. The method claims of the of the reference ‘861 patent, 9-18, 24-33 and 39-48 anticipate instant method claims 11-18.
The instant claims 1-2 and 6-18 and claims 1-48 of U.S. Patent No. 12,030,861 B1 are therefore not patentably distinct.
This is a nonstatutory double patenting rejection.
Claims 1-2 and 6-18 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 21-22 and 26-39 of co-pending Application No 19/501,227 in view of Abou-Taleb et al. (Exploration of the Safety and Solubilization, Dissolution, Analgesic Effects of Common Basic Excipients on the NSAID Drug Ketoprofen, 20 February 2023, hereinafter Abou-Taleb, in the IDS) and Variankaval et al. (From Form to Function: Crystallization of Active Pharmaceutical Ingredients, July 2008, hereinafter Variankaval, in the IDS).
Although the claims at issue are not identical, they are not patentably distinct from each other.
The instant claims are drawn to an L-lysine salt of 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid, which is in a crystalline form in an embodiment, a process of preparation of the same, a pharmaceutical or veterinary composition and methods of treatment thereof.
The claims the co-pending Application No 19/501,227 are drawn to an L-arginine salt of 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid, which is in a crystalline form in an embodiment, a process of preparation of the same, a pharmaceutical or veterinary composition and methods of treatment thereof.
The claims of the co-pending ‘227 application does not recite an L-lysine salt of 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid or a crystalline form thereof.
Abou-Taleb teaches numerous solubilization techniques to improve the solubility and dissolution rates of different water-insoluble drugs, including salt formation (Pg. 2, first paragraph). Abou-Taleb further teaches successful use of amino acids in solubilizing both ionizable and non-ionizable drugs and a growing interest in utilizing amino acids due to their safety and tolerability (Pg. 2, second paragraph). Abou-Taleb teaches exploring L-lysine, L-arginine and tromethamine in improving the biopharmaceutical properties of ketoprofen (a weakly acidic drug) (Pg. 2, fifth paragraph; Pg. 5, second full paragraph). Abou-Taleb teaches the three basic excipients, tris, L-lysine, and L-arginine, at a concentration of 3% w/v, significantly (p < 0.05) improved the solubility of ketoprofen by 4, 4.65, and 6.8-fold, respectively (Pg. 5, second full paragraph). Abou-Taleb teaches all three basic excipients (tris, L-lysine, and L-arginine) as potential solubilizers for the NSAID ketoprofen (Pg. 13, last paragraph).
Variankaval teaches crystallization represents a convenient and scalable
method to purify a drug substance (Pg. 1683, second column, second full paragraph). Variankaval further teaches crystallinity confers various advantages during isolation, processing and storage of the drug, such as better impurity rejection, improved handling characteristics, such as sticking and flow and, in the majority of cases, better physical and chemical stability (Pg. 1682, second column, last paragraph).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, in view of the teachings of the co-pending ‘227 application, Abou-Taleb and Variankaval, to have explored the different amino acid solubilizers to arrive at the claimed L-lysine salt of 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid) (i.e., EYP001) with a reasonable expectation of success in enhancing the solubility and dissolution characteristics of EYP001 (EYP001 is inherently known to have low water solubility). The motivation being to improve the biopharmaceutical properties of EYP001, a weakly acidic drug (Pg. 2, fifth paragraph).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, in view of the teachings of the co-pending ‘227 application, Abou-Taleb and Variankaval, to have crystallized the L-lysine salt of EYP001 with a reasonable expectation of success in conferring better properties. The motivation being to provide a drug product with impeccable physicochemical stability and adequate shelf-life (Variankaval, Pg. 1687, continued paragraph).
Claims 26-27 of the co-pending ‘227 application render obvious instant claims 6-7 drawn to a process of preparation of an L-lysine salt of 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid in a crystalline form. Claims 28-30 of the co-pending ‘227 application render obvious instant claims 8-10 drawn to a pharmaceutical or veterinary composition thereof. The method claims of the of the co-pending ‘227 application, 31-39 render obvious instant method claims 11-18.
The instant claims 1-2 and 6-18 and claims 21-22 and 26-39 of co-pending Application No 19/501,227 are therefore not patentably distinct.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-2 and 8-18 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 25-26 and 36-44 of co-pending Application No 19/501,231 in view of Abou-Taleb et al. (Exploration of the Safety and Solubilization, Dissolution, Analgesic Effects of Common Basic Excipients on the NSAID Drug Ketoprofen, 20 February 2023, hereinafter Abou-Taleb, in the IDS) and Variankaval et al. (From Form to Function: Crystallization of Active Pharmaceutical Ingredients, July 2008, hereinafter Variankaval, in the IDS).
Although the claims at issue are not identical, they are not patentably distinct from each other.
The instant claims are drawn to an L-lysine salt of 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid, which is in a crystalline form in an embodiment, a pharmaceutical or veterinary composition and methods of treatment thereof.
The claims the co-pending Application No 19/501,231 are drawn to a tromethamine salt of 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid, which is in a crystalline form in an embodiment, a pharmaceutical or veterinary composition and methods of treatment thereof.
The claims of the co-pending ‘231 application does not recite an L-lysine salt of 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid or a crystalline form thereof.
Abou-Taleb teaches numerous solubilization techniques to improve the solubility and dissolution rates of different water-insoluble drugs, including salt formation (Pg. 2, first paragraph). Abou-Taleb further teaches successful use of amino acids in solubilizing both ionizable and non-ionizable drugs and a growing interest in utilizing amino acids due to their safety and tolerability (Pg. 2, second paragraph). Abou-Taleb teaches exploring L-lysine, L-arginine and tromethamine (tris) in improving the biopharmaceutical properties of ketoprofen (a weakly acidic drug) (Pg. 2, fifth paragraph; Pg. 5, second full paragraph). Abou-Taleb teaches the three basic excipients, tris, L-lysine, and L-arginine, at a concentration of 3% w/v, significantly (p < 0.05) improved the solubility of ketoprofen by 4, 4.65, and 6.8-fold, respectively (Pg. 5, second full paragraph). Abou-Taleb teaches all three basic excipients (tris, L-lysine, and L-arginine) as potential solubilizers for the NSAID ketoprofen (Pg. 13, last paragraph).
Variankaval teaches crystallization represents a convenient and scalable
method to purify a drug substance (Pg. 1683, second column, second full paragraph). Variankaval further teaches crystallinity confers various advantages during isolation, processing and storage of the drug, such as better impurity rejection, improved handling characteristics, such as sticking and flow and, in the majority of cases, better physical and chemical stability (Pg. 1682, second column, last paragraph).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, in view of the teachings of the co-pending ‘231 application, Abou-Taleb and Variankaval, to have explored the different amino acid solubilizers to arrive at the claimed tromethamine salt of 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid) (i.e., EYP001) with a reasonable expectation of success in enhancing the solubility and dissolution characteristics of EYP001 (EYP001 is inherently known to have low water solubility). The motivation being to improve the biopharmaceutical properties of EYP001, a weakly acidic drug (Pg. 2, fifth paragraph).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, in view of the teachings of the co-pending ‘231 application, Abou-Taleb and Variankaval, to have crystallized the tromethamine salt of EYP001 with a reasonable expectation of success in conferring better properties. The motivation being to provide a drug product with impeccable physicochemical stability and adequate shelf-life (Variankaval, Pg. 1687, continued paragraph).
Claims 36-38 of the co-pending ‘231 application render obvious instant claims 8-10 drawn to a pharmaceutical or veterinary composition thereof. The method claims of the of the co-pending ‘231 application, 39-44 render obvious instant method claims 11-18.
The instant claims 1-2 and 8-18 and claims 25-26 and 36-44 of co-pending Application No 19/501,231 are therefore not patentably distinct.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-2, 8-11 and 15-18 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 16, 18-19, 26, 31, 33 and 35 of co-pending Application No 17/910,385 in view of Abou-Taleb et al. (Exploration of the Safety and Solubilization, Dissolution, Analgesic Effects of Common Basic Excipients on the NSAID Drug Ketoprofen, 20 February 2023, hereinafter Abou-Taleb, in the IDS), Variankaval et al. (From Form to Function: Crystallization of Active Pharmaceutical Ingredients, July 2008, hereinafter Variankaval, in the IDS), Vonderscher et al. (US 2022/0249469 A1, publication date 11 August 2022 and PCT filing date 17 July 2020, hereinafter Vonderscher, in the IDS) and Brees et al. (US 2022/0265619 A1, publication date 25 August 2022, hereinafter Brees, in the IDS).
Although the claims at issue are not identical, they are not patentably distinct from each other.
The instant claims are drawn to an L-lysine salt of 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid, which is in a crystalline form in an embodiment, a pharmaceutical or veterinary composition and methods of treating a disease selected from the group, that includes a renal disease (more specifically, Chronic Kidney Disease (CKD) comprising administering the L-lysine salt of 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid to a subject in need of treatment.
The claims of the co-pending Application No 17/910,385 are drawn to a method of treating a subject having a renal disease, comprising administering a therapeutic amount of a 4-halogeno-5-[4-(2,6-dichloro-benzenesulfonyl)- piperazin-1-yl]-benzofuran-2-carboxylic acid compound or a pharmaceutically salt thereof to said subject. The co-pending Application No 17/910,385 is further drawn to 4-chloro-5-[4- (2,6-dichloro-benzenesulfonyl)-piperazin-1-yl]-benzofuran-2-carboxylic acid or a pharmaceutically salt thereof (as in claim 18) and wherein the renal disease is a chronic kidney disease (CKD)/Alport’s syndrome (claim 19, 31, 33, 35).
The claims of the co-pending Application No 17/910,385 does not recite an L-lysine salt of 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid.
Abou-Taleb teaches numerous solubilization techniques to improve the solubility and dissolution rates of different water-insoluble drugs, including salt formation (Pg. 2, first paragraph). Abou-Taleb further teaches successful use of amino acids in solubilizing both ionizable and non-ionizable drugs (Pg. 2, second paragraph). Abou-Taleb further teaches the L-lysine salt of a small molecule (ketoprofen, a weakly acidic drug) having a carboxylic acid functional group to have enhanced solubility and improved dissolution rates (Pg. 2, third paragraph; Pg. 13, last paragraph). Abou-Taleb further teaches the ketoprofen lysine salt demonstrated more rapid and complete absorption than the acid form, attaining peak plasma concentrations faster (Pg. 10, second paragraph).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, in view of the teachings of the co-pending ‘385 application and Abou-Taleb to have arrived at the claimed method of treating a renal disease, comprising administering an L-lysine salt of 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid with a reasonable expectation of success in treating such conditions. The motivation being to provide the 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid in a more suitable form with improved solubility and dissolution profile. This renders instant method claims 11, 15-16 prima facie obvious.
The claims of the co-pending Application No 17/910,385 does not recite an L-lysine salt of 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid in a crystalline form.
Variankaval teaches crystallization represents a convenient and scalable
method to purify a drug substance (Pg. 1683, second column, second full paragraph). Variankaval further teaches crystallinity confers various advantages during isolation, processing and storage of the drug, such as better impurity rejection, improved handling characteristics, such as sticking and flow and, in the majority of cases, better physical and chemical stability (Pg. 1682, second column, last paragraph).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, in view of the teachings of the co-pending ‘385 application, Abou-Taleb and Variankaval to have crystallized the L-lysine salt of EYP001 (i.e., 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid) with a reasonable expectation of success in conferring better properties.
The claims of the co-pending Application No 17/910,385 does not recite a pharmaceutical or veterinary composition comprising the L-lysine salt or a combination composition thereof.
Vonderscher further teaches pharmaceutical compositions of EYP001 combined with pharmaceutically acceptable excipients (Para. [0036]). Vonderscher teaches EYP001 can be used in combination with an additional active ingredient, wherein the additional active ingredient is a TLR7, TLR8 or TLR9 agonist, a RIG-I modulator, a STING agonist, an interferon , preferably IFN-α or a pegylated form thereof (Para. [0011]; Paras. [0060]-[0061]; Para. [0063]).
Brees teaches a method for the treatment of a condition mediated by farnesoid X receptors (FXR), in particular liver diseases or intestinal diseases, e.g. NASH comprising administering to a subject in need thereof a pharmaceutical combination comprising : an FXR agonist and an SGLT inhibitor, e.g. SGLT 1/2 inhibitor (Paras. [0027]-[0029]; Claim 15; Claim 1). Brees teaches wherein the FXR agonist can be PXL007 (Para. [0036]; Para. [0134]; Claim 1) (i.e., EYP001 or 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid, see page 1, lines 14-16 of instant specification).
Therefore the combined teachings of the co-pending ‘385 application, Abou-Taleb and Variankaval in view of Vonderscher and Brees render obvious a pharmaceutical composition comprising the L-lysine salt or a combination composition thereof as in the instant claims 8-10 and 16, and treatment of additional conditions as in instant claim 17 using the L-lysine salt of the instant claims.
The instant claims 1-2, 8-11 and 15-18 and claims 16, 18-19, 26, 31, 33 and 35 of co-pending Application No 17/910,385 are therefore not patentably distinct.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-2, 8-14, 16 and 18 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 16 and 19-21 of co-pending Application No 17/787,956 in view of Abou-Taleb et al. (Exploration of the Safety and Solubilization, Dissolution, Analgesic Effects of Common Basic Excipients on the NSAID Drug Ketoprofen, 20 February 2023, hereinafter Abou-Taleb, in the IDS).
Although the claims at issue are not identical, they are not patentably distinct from each other.
The instant claims are drawn to an L-lysine salt of 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid, which is in a crystalline form in an embodiment, a pharmaceutical or veterinary composition and methods of treating a disease selected from the group, that includes a renal disease (more specifically, Chronic Kidney Disease (CKD) comprising administering the L-lysine salt of 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid to a subject in need of treatment.
The claims of the co-pending Application No 17/787,956 are drawn to a method for the treatment of Hepatitis D virus (HDV) infection in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a farnesoid X receptor (FXR) agonist, wherein the FXR agonist is EYP001 (i.e., 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid) (claims 16, 19-20); further drawn to wherein said FXR agonist is administered in combination with an interferon alpha (IFN-a), an interferon lambda or a pegylated form thereof (claim 21).
The co-pending Application No 17/787,956 does not recite an L-lysine salt of EYP001 (i.e.,4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid).
Vonderscher teaches EYP001 (i.e., 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid, see page 1, lines 14-16 of instant specification) and indicates EYP001 refers to this compound and any pharmaceutically acceptable salt thereof (Paras. [0016]-[0017]) (EYP001 is inherently known to have low water solubility).
Abou-Taleb teaches numerous solubilization techniques to improve the solubility and dissolution rates of different water-insoluble drugs, including salt formation (Pg. 2, first paragraph). Abou-Taleb further teaches successful use of amino acids in solubilizing both ionizable and non-ionizable drugs (Pg. 2, second paragraph). Abou-Taleb further teaches the L-lysine salt of a small molecule (ketoprofen, a weakly acidic drug) having a carboxylic acid functional group to have enhanced solubility and improved dissolution rates (Pg. 2, third paragraph; Pg. 13, last paragraph). Abou-Taleb further teaches the ketoprofen lysine salt demonstrated more rapid and complete absorption than the acid form, attaining peak plasma concentrations faster (Pg. 10, second paragraph).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, in view of the teachings of the co-pending ‘956 application, Vonderscher and Abou-Taleb to have arrived at the claimed method of treating a Hepatitis D virus (HDV) infection in a subject in need thereof, comprising administering an L-lysine salt of 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid with a reasonable expectation of success in treating such conditions. The motivation being to provide the 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid in a more suitable form with improved solubility and dissolution profile. This renders instant method claims 11-14, 16 prima facie obvious.
The claims of the co-pending Application No 17/787,956 does not recite an L-lysine salt of 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid in a crystalline form.
Variankaval teaches crystallization represents a convenient and scalable
method to purify a drug substance (Pg. 1683, second column, second full paragraph). Variankaval further teaches crystallinity confers various advantages during isolation, processing and storage of the drug, such as better impurity rejection, improved handling characteristics, such as sticking and flow and, in the majority of cases, better physical and chemical stability (Pg. 1682, second column, last paragraph).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, in view of the teachings of the co-pending ‘956 application, Vonderscher, Abou-Taleb and Variankaval to have crystallized the L-lysine salt of EYP001 (i.e., 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid) with a reasonable expectation of success in conferring better properties.
The claims of the co-pending Application No 17/787,956 does not recite a pharmaceutical or veterinary composition comprising the L-lysine salt or a combination composition thereof.
Vonderscher further teaches pharmaceutical compositions of EYP001 combined with pharmaceutically acceptable excipients (Para. [0036]). Vonderscher teaches EYP001 can be used in combination with an additional active ingredient, wherein the additional active ingredient is a TLR7, TLR8 or TLR9 agonist, a RIG-I modulator, a STING agonist, an interferon , preferably IFN-α or a pegylated form thereof (Para. [0011]; Paras. [0060]-[0061]; Para. [0063]).
Brees teaches a method for the treatment of a condition mediated by farnesoid X receptors (FXR), in particular liver diseases or intestinal diseases, e.g. NASH comprising administering to a subject in need thereof a pharmaceutical combination comprising : an FXR agonist and an SGLT inhibitor, e.g. SGLT 1/2 inhibitor (Paras. [0027]-[0029]; Claim 15; Claim 1). Brees teaches wherein the FXR agonist can be PXL007 (Para. [0036]; Para. [0134]; Claim 1) (i.e., EYP001 or 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid, see page 1, lines 14-16 of instant specification).
Therefore the combined teachings of the co-pending ‘956 application, Vonderscher, Abou-Taleb and Variankaval in view of and Brees render obvious a pharmaceutical composition comprising the L-lysine salt or a combination composition thereof as in the instant claims 8-10 and 16, and treatment of additional conditions as in instant claim 17 using the L-lysine salt of the instant claims.
The instant claims 1-2, 8-14 and 16-18 and claims 16 and 19-21 of co-pending Application No 17/787,956 are therefore not patentably distinct.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-2 and 11-18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 3-7 of U.S. Patent No. 12,551,480 B2 in view of Abou-Taleb et al. (Exploration of the Safety and Solubilization, Dissolution, Analgesic Effects of Common Basic Excipients on the NSAID Drug Ketoprofen, 20 February 2023, hereinafter Abou-Taleb, in the IDS).
Although the claims at issue are not identical, they are not patentably distinct from each other.
The instant claims are drawn to an L-lysine salt of 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid, which is in a crystalline form in an embodiment, a pharmaceutical or veterinary composition and methods of treatment thereof.
The claims of the reference ‘480 patent are drawn to a method of treating a patient comprising the administration of EYP001 (i.e.,4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid) to said patient wherein the disease selected from a group consisting of chronic liver disease, gastrointestinal disease, renal disease, cardiovascular disease, metabolic disease and infectious disease. The reference ‘480 patent is further drawn to administering EYP001 in combination with an immunomodulators (claims 4-6). The reference ‘480 patent contemplates administering EYP001 and a pharmaceutically acceptable salt thereof (Col. 3, Lns. 40-41).
The reference ‘480 patent does not recite an L-lysine salt of EYP001 (i.e.,4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid).
Abou-Taleb teaches numerous solubilization techniques to improve the solubility and dissolution rates of different water-insoluble drugs, including salt formation (Pg. 2, first paragraph). Abou-Taleb further teaches successful use of amino acids in solubilizing both ionizable and non-ionizable drugs (Pg. 2, second paragraph). Abou-Taleb further teaches the L-lysine salt of a small molecule (ketoprofen, a weakly acidic drug) having a carboxylic acid functional group to have enhanced solubility and improved dissolution rates (Pg. 2, third paragraph; Pg. 13, last paragraph). Abou-Taleb further teaches the ketoprofen lysine salt demonstrated more rapid and complete absorption than the acid form, attaining peak plasma concentrations faster (Pg. 10, second paragraph).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, in view of the teachings of the reference ‘480 patent and Abou-Taleb to have arrived at the claimed method of treating a condition as in instant claim 11 in a subject in need thereof, comprising administering an L-lysine salt of 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid with a reasonable expectation of success in treating such conditions. The motivation being to provide the 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid in a more suitable form with improved solubility and dissolution profile. This renders instant method claims 11-14, 17 prima facie obvious.
The claims of the reference ‘480 patent does not recite an L-lysine salt of 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid in a crystalline form.
Variankaval teaches crystallization represents a convenient and scalable
method to purify a drug substance (Pg. 1683, second column, second full paragraph). Variankaval further teaches crystallinity confers various advantages during isolation, processing and storage of the drug, such as better impurity rejection, improved handling characteristics, such as sticking and flow and, in the majority of cases, better physical and chemical stability (Pg. 1682, second column, last paragraph).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, in view of the teachings of the reference ‘480 patent, Abou-Taleb and Variankaval to have crystallized the L-lysine salt of EYP001 (i.e., 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid) with a reasonable expectation of success in conferring better properties.
The instant claims 1-2, 11-18 and claims 1 and 3-7 of U.S. Patent No. 12,551,480 B2 are therefore not patentably distinct.
This is a nonstatutory double patenting rejection.
Objection to Claims, Allowable Subject Matter
Except for the statutory double patenting rejections, claims 3-5 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The crystalline form of an L-lysine salt of 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid (i.e., EYP001) characterized the X-ray diffraction pattern as in instant claims 3-5, has been found to be free of prior art.
The following is a statement of reasons for the indication of allowable subject matter:
The closest prior art is Vonderscher et al. (US 2022/0249469 A1, publication date 11 August 2022 and PCT filing date 17 July 2020, hereinafter Vonderscher) and Abou-Taleb et al. (Exploration of the Safety and Solubilization, Dissolution, Analgesic Effects of Common Basic Excipients on the NSAID Drug Ketoprofen, 20 February 2023, hereinafter Abou-Taleb).
Vonderscher teaches EYP001 (i.e., 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid) and indicates EYP001 refers to this compound and any pharmaceutically acceptable salt thereof (Paras. [0016]-[0017]).
Abou-Taleb teaches numerous solubilization techniques to improve the solubility and dissolution rates of different water-insoluble drugs, including salt formation (Pg. 2, first paragraph). Abou-Taleb further teaches successful use of amino acids in solubilizing both ionizable and non-ionizable drugs (Pg. 2, second paragraph). Abou-Taleb further teaches the L-lysine salt of a small molecule (ketoprofen) having a carboxylic acid functional group to have enhanced solubility and improved dissolution rates (Pg. 13, last paragraph).
However, there is no teaching or suggestion in the prior art regarding crystalline forms of an L-lysine salt of 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid (i.e., EYP001) characterized by the properties of X-ray diffraction pattern as in instant claims 3-5 or a process for obtaining the same. Therefore, the crystalline forms of an L-lysine salt of 4-chloro-5-[4-(2,6-dichlorophenyl)sulfonylpiperazin-1-yl]-1-benzofuran-2-carboxylic acid (i.e., EYP001) as in instant claims 3-5 are novel and non-obvious over the closest prior art.
Conclusion
Claims 1-18 are rejected.
Claims 3-5 are objected to.
No claims are allowed.
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/PADMAJA S RAO/Examiner, Art Unit 1627
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