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 Application
Claims 1, 3, 5, 11-12, 21, 26-29 and 32-40 are pending in the application as of the preliminary amendment submitted 12/05/2025. Claims 2, 4, 6-10, 13-20, 22-25 and 30-31 are cancelled. Claims 1, 3, 5, 11-12, 21, 26-29 and 32-40 are examined herein.
Priority
This application is a 371 of PCT/CN2022/141418 filed 12/23/2022 and claims foreign priority to CHINA 202111584574.4 filed 12/23/2021.
Acknowledgment is made of applicant's claim for foreign priority based on an application filed in CHINA on 12/23/2021. It is noted that Applicants have not provided an English translation of the certified copy of the foreign priority application as required by 35 U.S.C. 119(b). Without the English translation, one cannot ascertain if the instant invention is supported in the non-English foreign application. Therefore, art prior to the PCT date, but not before the date of the non-English application may be cited against the claims. Accordingly, claims 1, 3, 5, 11-12, 21, 26-29 and 32-40 have been afforded an effective filing date of 12/23/2022, the filing date of the PCT application.
Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d), a certified English translation of the foreign application may be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e).
Information Disclosure Statement
The information disclosure statements submitted on 06/06/2025, 04/10/2025, 11/25/2024 and 06/20/2024 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 - Enablement
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 34-39 are rejected 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 treating a disease associated with GLP-1 receptor agonism in a subject in need thereof OR a method for treating diabetes in a subject in need thereof, comprising administering pharmaceutically acceptable salt or the crystal forms thereof, does not reasonably provide enablement for a method of treating and preventing a disease associated with GLP-1 receptor or preventing diabetes in a subject in need thereof. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims. This is a scope of enablement rejection.
To be enabling, the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fed. Cir. 1993). The determination that "undue experimentation” would have been needed to practice the claimed invention in full scope is not a single, simple factual determination.
As stated in the MPEP 2164.01(a), “There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is "undue." In re Wands, 8 USPQe2d 1400 (1988), factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have need described. They are:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. Keeping that in mind, the Wands factors are relevant to the instant application for the following reasons:
The breadth of the claims/The nature of the invention
Claims 34-39 are drawn to a method for treating or preventing a disease associated with GLP-1 receptor in a subject in need thereof OR a method for treating or preventing diabetes in a subject in need thereof, comprising administering a pharmaceutically acceptable salt of 2-((4-(S)-3-(4-chloro-2-fluorophenyl)-2,3-dihydrobenzo[b][1,4]dioxan-5-yl)piperidin-1-yl)methyl)-1-(((S)-oxetan-2-yl)methyl)-1H-benzo[d]imidazole-6-carboxylic acid or the crystal forms thereof to the subject. The claims are drawn broadly to treating and preventing any disease associated with a GLP-1 receptor (i.e., a condition that responds to any of GLP-1 agonism or inhibition). Moreover, the instant specification does not provide a definition for the limitation “preventing”, which is being given the broadest reasonable interpretation which includes stopping a disease or disorder from ever occurring.
The state of the prior art/The level of predictability in the art
Karalliedde et al. (Diabetes mellitus, a complex and heterogeneous disease, and the role of insulin resistance as a determinant of diabetic kidney disease, 30 December 2014, hereinafter Karalliedde).
Skyler et al. (Differentiation of Diabetes by Pathophysiology, Natural History, and Prognosis, Diabetes, February 2017, hereinafter Skyler).
Karalliedde teaches diabetes mellitus (DM) as a heterogeneous condition with diverse clinical presentations (Abstract). Karalliedde teaches individualization of care and treatment necessitates an understanding of the individual patient’s pathophysiology of DM that underpins their DM classification and clinical presentation (Abstract).
Skyler teaches there are many different paths driven by various genetic and environmental factors that result in the progressive loss of β-cell mass and/or function that manifests clinically as hyperglycemia (Pg. 241, second column, first full paragraph). Skyler teaches research efforts are needed to define causative factors that account for the established correlations among different demographic subsets and the corresponding variable risks for diabetes (Pg. 243, first column, sixth paragraph).
Therefore, prevention of diabetes is not well-established or predictable in consideration of the art. It is unclear how the claimed method would achieve prevention of the disease, since the current state of the art teach that the prevention of all types of diabetes through the modulation of a single pathway (say, GLP-1 modulation) would be doubtful since diabetes mellitus (DM) is a heterogeneous condition with diverse clinical presentations. The prior art does not support the basis of the instant invention drawn to the prevention of a disease associated with GLP-1 receptor and/or diabetes through the administration of a GLP-1 agonist.
The level of one of ordinary skill in the art
The relative level of skill in the art is high, such as, a molecular biologist/molecular geneticist with advanced educational degrees (e.g., M.D. and/or Ph.D.).
The amount of direction provided by the inventor/The existence of working examples
The specification in Paras. [0211]-[0218], indicates that Compound A, the tromethamine salt of the instant claims show GLP-1 agonism in an in vitro assay. The instant specification does not provide any working examples of treatment of any and all diseases associated with GLP-1 receptor or the prevention of these diseases, nor does it provide adequate guidance on how to overcome the art-recognized challenges in this regard. One of ordinary skilled in the art would not be able to practice the method of the claims to achieve the intended result of treating or preventing a disease associated with GLP-1 receptor in a subject in need thereof OR a method for preventing diabetes in a subject in need thereof, as claimed.
The quantity of experimentation needed
Considering the state of the art as discussed in the prior art references above, and the high degree of unpredictability in the art and the lack of direction or guidance in the specification regarding how the administration of a pharmaceutically acceptable salt of 2-((4-(S)-3-(4-chloro-2-fluorophenyl)-2,3-dihydrobenzo[b][1,4]dioxan-5-yl)piperidin-1-yl)methyl)-1-(((S)-oxetan-2-yl)methyl)-1H-benzo[d]imidazole-6-carboxylic acid or the crystal forms thereof to the subject in need thereof results in the intended treatment effects, one of ordinary skill in the art would be burdened with undue experimentation to practice the invention commensurate in scope with the claims.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 5, 11-12, 26-29 and 32-37 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 5, the claim recites the limitation “an X-ray powder diffraction pattern of the crystal form expressed with diffraction angle 2θ has characteristic peaks at 6.850, 9.982, …; preferably characteristic peaks at 6.850, 9.982, …; more preferably characteristic peaks at 6.850, 8.051, …”. The recitation of the limitation “preferably” or “more preferably” in several instances renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). Thus, the metes and bounds of the claims are unclear.
For the purpose of applying prior art, claim 5 been interpreted to
exclude the language that follows the limitation “preferably” or “more preferably”.
Claims 11, 26-27, 32 and 34-35 depend from the rejected base claim and are similarly rejected since they do not remedy the indefiniteness.
Regarding claim 12, the claim recites the limitation “(1) the crystal form is a potassium salt and an X-ray powder diffraction pattern of the crystal form expressed with diffraction angle 2θ has characteristic peaks at 9.564, 11.515, …; preferably characteristic peaks at 9.564, 11.515, …; more preferably characteristic peaks at 9.564, 11.515, …; (3) the crystal form is a sodium salt and an X-ray powder diffraction pattern of the crystal form expressed with diffraction angle 2θ has characteristic peaks at 9.754, 11.731, …; preferably characteristic peaks at 5.574, 9.754, 11.515, …”. The recitation of the limitation “preferably” or “more preferably” in several instances renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). Thus, the metes and bounds of the claims are unclear.
For the purpose of applying prior art, claim 12 been interpreted to
exclude the language that follows the limitation “preferably” or “more preferably”.
Claims 28-29, 33 and 36-37 depend from the rejected base claim and are similarly rejected since they do not remedy the indefiniteness.
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.
Claims 1, 3, 21 and 38-40 are rejected under 35 U.S.C. 103 as being unpatentable over Su et al. (WO 2022/228490 A1, publication date 03 November 2022 and international filing date of 28 April 2022, hereinafter Su, in the IDS) in view of Aspnes et al. (WO 2019/239319 A1, 19 December 2019, hereinafter Aspnes, in the IDS) (Su qualifies as prior art under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) with a publication date of 03 November 2022 and international filing date of 28 April 2022, both of which precede the effective filing date of the instant application, 12/23/2022) (Citations are made to the attached English translation).
The examiner notes that the Su reference will continue to qualify as 35 U.S.C. 102(a)(2) prior art even if the claim for foreign priority were perfected, since the subject matter used in this rejection is supported in the foreign priority application of Su, CN202100235614.4 filed 22 October 2021 (available in WIPO Patentscope).
Regarding instant claims 1 and 3, Su teaches a compound of general formula (I-D), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, with variables as defined (Paras. [0009]-[0041]). Su teaches the compounds act as GLP-1 receptor agonists (Para. [0287]; Para. [3658]). Su teaches the following exemplary compound (Claim 14, Pg. 250).
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The above compound of Su anticipates instant compound, 2-((4-(S)-3-(4-chloro-2-fluorophenyl)-2,3-dihydrobenzo[b][1,4]dioxan-5-yl)piperidin-1-yl)methyl)-1-(((S)-oxetan-2-yl)methyl)-1H-benzo[d]imidazole-6-carboxylic acid, of claim 1, as evidenced by Para. [0005] of the instant specification that teaches the compound of the instant claims having the structure shown below.
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Su do not explicitly teach wherein the pharmaceutically acceptable salt is selected from a tromethamine salt, an ammonium salt, a potassium salt, an arginine salt, a sodium salt, a meglumine salt, an ethanolamine salt, a p-toluenesulfonate salt, a tartrate salt, a sulfate salt, a malate salt, and a hydrochloride salt.
Aspnes teaches 6-carboxylic acids of benzimidazoles or a pharmaceutically acceptable salt thereof, as GLP-1 R agonists (Abstract; Pg. 3, Ln. 23 - Pg. 5, Ln. 7). Aspnes teaches structurally related heterocyclic compounds differing in the size of the oxygen-containing ring fused to the benzene ring (Pg. 16, Lns. 15-17). Aspnes teaches suitable acid addition salts to include hydrochloride, … malate, … tartrate, tosylate, … (Pg. 24, Lns. 18-25). Aspnes teaches suitable base salts to include arginine, … meglumine, … potassium, sodium, 2-Amino-2-(hydroxymethyl)propane-1 ,3-diol (tris or tromethamine) salts (Pg. 24, Lns. 27-30). Aspnes teaches a method of preparing the pharmaceutically acceptable salts by reacting the compounds with the desired acid or base (Pg. 24, Lns. 34-36).
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 Su and Aspnes to have synthesized the specific pharmaceutically acceptable salts, say, hydrochloride, malate, tartrate, tosylate, arginine, meglumine, potassium, sodium and tromethamine, to arrive at the pharmaceutically acceptable salts of the instant claims with a reasonable expectation of success. Su teaches compounds and pharmaceutically acceptable salts thereof, that act as GLP-1 receptor agonists. Su teaches an exemplary compound that anticipates instant compound, 2-((4-(S)-3-(4-chloro-2-fluorophenyl)-2,3-dihydrobenzo[b][1,4]dioxan-5-yl)piperidin-1-yl)methyl)-1-(((S)-oxetan-2-yl)methyl)-1H-benzo[d]imidazole-6-carboxylic acid. Aspnes teaches substantially structurally similar 6-carboxylic acids of benzimidazoles or a pharmaceutically acceptable salt thereof, as GLP-1 R agonists. Aspnes teaches suitable acid addition salts to include hydrochloride, malate, tartrate, tosylate, and suitable base salts to include arginine, meglumine, potassium, sodium, tromethamine salts. Therefore, one of ordinary skill in the art would have been motivated to synthesize the instantly claimed pharmaceutically acceptable salts. The motivation being to optimize their physicochemical, biopharmaceutical, and manufacturing properties.
Regarding instant claims 21 and 40, Su in view of Aspnes, renders the pharmaceutically acceptable salt of instant claim 1, prima facie obvious. Su teaches pharmaceutical compositions comprising a therapeutically effective dose of the compound of any one of claims 1-14, a stereoisomer thereof or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers or excipients (Claim 18, Pg. 251; Para. [0368]). Su teaches the pharmaceutical compositions as a mixture containing the compounds or pharmaceutically acceptable salts as well as other components such as physiological/pharmaceutically acceptable carriers and excipients (Para. [0368]). The teaching of a “mixture” indicates the composition is prepared by mixing the active ingredient with an excipient. Therefore, the limitations of instant claims 21 and 40 are rendered prima facie obvious.
Regarding instant claims 38-39, Su in view of Aspnes, renders the pharmaceutically acceptable salt of instant claim 1, prima facie obvious. Su teaches methods of treating a disease condition including, but not limited to conditions related to GLP-1 receptor modulators using the compounds or pharmaceutical compositions of the invention (Para. [0291]). Su teaches methods of treating metabolic-related diseases, wherein the disease is selected from diabetes Therefore, the limitations of instant claims 38-39 are rendered prima facie obvious.
Claims 1, 3, 21 and 38-40 are rejected under 35 U.S.C. 103 as being unpatentable over Jennings et al. (WO 2021/219019 A1, 04 November 2021, hereinafter Jennings, in the IDS) in view of Aspnes et al. (WO 2019/239319 A1, 19 December 2019, hereinafter Aspnes, in the IDS) (Jennings qualifies as prior art under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) with a publication date of 04 November 2021 and international filing date of 28 April 2021, both of which precede the effective filing date of the instant application, 12/23/2022).
The examiner notes that the Jennings reference will continue to qualify as prior art even if the claim for foreign priority were perfected.
Regarding instant claims 1 and 3, Jennings teaches heterocyclic GLP-1 agonists of Formula (I), including pharmaceutically acceptable salts (Abstract; Pg. 2, Ln. 1 - Pg. Ln. 26).
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Jennings teaches an exemplary compound, compound 120c (Pg. 66, Table C2; Pg. 141, Lns. 6-18).
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Compound 120c of Jennings is an isomer of the instant compound, 2-((4-(S)-3-(4-chloro-2-fluorophenyl)-2,3-dihydrobenzo[b][1,4]dioxan-5-yl)piperidin-1-yl)methyl)-1-(((S)-oxetan-2-yl)methyl)-1H-benzo[d]imidazole-6-carboxylic acid, of claim 1. Para. [0005] of the instant specification teaches the compound of the instant claims having the structure shown below.
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Compound 120c of Jennings differs from the instant compound in the position of the 4-chloro-2-fluorophenyl group being in the 2- versus the 3- position of the 2,3-dihydrobenzo[b][1,4]dioxan-5-yl ring, as instantly claimed.
According to MPEP 2144.09 (III), “Prior art structures do not have to be true homologs or isomers to render structurally similar compounds prima facie obvious. In re Payne, 606 F.2d 303, 203 USPQ 245 (CCPA 1979). See also In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986) (claimed and prior art compounds used in a method of treating depression would have been expected to have similar activity because the structural difference between the compounds involved a known bioisosteric replacement)”.
Further according to MPEP 2144.09 (I), “A prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. "An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties." In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979).” In the instant case, the compounds of Jennings are taught to be GLP-1 agonists, identical in utility to that of the instant compounds. The compound of Jennings is a positional isomer of the instant compound, therefore, rendering it prima facie obvious.
Jennings do not explicitly teach wherein the pharmaceutically acceptable salt is selected from a tromethamine salt, an ammonium salt, a potassium salt, an arginine salt, a sodium salt, a meglumine salt, an ethanolamine salt, a p-toluenesulfonate salt, a tartrate salt, a sulfate salt, a malate salt, and a hydrochloride salt.
Aspnes teaches 6-carboxylic acids of benzimidazoles or a pharmaceutically acceptable salt thereof, as GLP-1 R agonists (Abstract; Pg. 3, Ln. 23 - Pg. 5, Ln. 7). Aspnes teaches structurally related heterocyclic compounds differing in the size of the oxygen-containing ring fused to the benzene ring (Pg. 16, Lns. 15-17). Aspnes teaches suitable acid addition salts to include hydrochloride, … malate, … tartrate, tosylate, … (Pg. 24, Lns. 18-25). Aspnes teaches suitable base salts to include arginine, … meglumine, … potassium, sodium, 2-Amino-2-(hydroxymethyl)propane-1 ,3-diol (tris or tromethamine) salts (Pg. 24, Lns. 27-30). Aspnes teaches a method of preparing the pharmaceutically acceptable salts by reacting the compounds with the desired acid or base (Pg. 24, Lns. 34-36).
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 Jennings and Aspnes to have synthesized the specific pharmaceutically acceptable salts, say, hydrochloride, malate, tartrate, tosylate, arginine, meglumine, potassium, sodium and tromethamine, to arrive at the pharmaceutically acceptable salts of the instant claims with a reasonable expectation of success. Jennings teaches heterocyclic GLP-1 agonists of Formula (I), including pharmaceutically acceptable salts. Jennings teaches an exemplary compound, compound 120c, which is a positional isomer of the instantly claimed compound. Aspnes teaches substantially structurally similar 6-carboxylic acids of benzimidazoles or a pharmaceutically acceptable salt thereof, as GLP-1 R agonists. Aspnes teaches suitable acid addition salts to include hydrochloride, malate, tartrate, tosylate, and suitable base salts to include arginine, meglumine, potassium, sodium, tromethamine salts. Therefore, one of ordinary skill in the art would have been motivated to synthesize the instantly claimed pharmaceutically acceptable salts. The motivation being to optimize their physicochemical, biopharmaceutical, and manufacturing properties.
According to MPEP 2144.05(II)(A), "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Therefore, it would have taken no more than the relative skills of one of ordinary skill in the art through routine experimentation to have arrived at the suitable pharmaceutically acceptable salt forms of 2-((4-(S)-3-(4-chloro-2-fluorophenyl)-2,3-dihydrobenzo[b][1,4]dioxan-5-yl)piperidin-1-yl)methyl)-1-(((S)-oxetan-2-yl)methyl)-1H-benzo[d]imidazole-6-carboxylic acid, given the teachings of the prior art.
Regarding instant claims 21 and 40, Jennings in view of Aspnes, renders the pharmaceutically acceptable salt of instant claim 1, prima facie obvious. Jennings teaches pharmaceutical compositions comprising a compound of Formula I, or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable excipient (Pg. 4, Lns. 28-30). Jennings teaches the pharmaceutical compositions are prepared by mixing the active ingredient with an excipient or diluted by an excipient (Pg. 70, Lns. 8-18; Pg. 70, Lns. 28-32). Therefore, the limitations of instant claims 21 and 40 are rendered prima facie obvious.
Regarding instant claims 38-39, Jennings in view of Aspnes, renders the pharmaceutically acceptable salt of instant claim 1, prima facie obvious. Jennings teaches methods for treating GLP-1 associated diseases, disorders, and conditions by administering to the patient a therapeutically effective amount of a compound of Formula I, or a pharmaceutically acceptable salt or solvate thereof, or a pharmaceutical composition thereof (Pg. 2, Lns. 1-5; Pg. 5, Lns. 1-19). Therefore, the limitations of instant claims 38-39 are rendered prima facie obvious.
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 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, 3, 21 and 38-40 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 and 16-18 of U.S. Patent No. 12,227,499 B2 in view of Aspnes et al. (WO 2019/239319 A1, 19 December 2019, hereinafter Aspnes, in the IDS).
Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are drawn to compounds having similar core structures.
The instant claims are drawn to a pharmaceutically acceptable salt of compound 2-(4-(S)-3-(4-chloro-2-fluorophenyl)-2,3-dihydrobenzofblf1,4]dioxan-5-yl)piperidin-1-yl)methyl)-1-((S)-oxetan-2-yl)methyl)-1H-benzo[d]imidazole-6-carboxylic acid, wherein the pharmaceutically acceptable salt is selected from a tromethamine salt, an ammonium salt, a potassium salt, an arginine salt, a sodium salt, a meglumine salt, an ethanolamine salt, a p-toluenesulfonate salt, a tartrate salt, a sulfate salt, a malate salt, and a hydrochloride salt, a method of preparation thereof, pharmaceutical compositions and methods of use thereof.
The claims of the reference ‘499 patent are drawn to a compound of general formula (IM) or a tautomer, racemate, enantiomer or diastereomer thereof or a mixture thereof, or a pharmaceutically acceptable salt thereof.
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Claim 13 of the reference ‘499 patent teaches the following exemplary compounds with close structural similarity to the instant compounds (Col. 219; Col. 221).
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Looking into the disclosure of the ‘499 patent for the utility of the compounds, the ‘499 patent teaches the compounds of general formula (IM) as GLP-1 receptor agonists (Col. 98, Lns. 19-30).
The exemplary compounds of the reference ‘499 patent differ from the instant compound in the presence or absence of a methyl group on the piperidine ring or a piperazine versus a piperidine of the instant claims.
According to MPEP 2144.09 (III), “Prior art structures do not have to be true homologs or isomers to render structurally similar compounds prima facie obvious. In re Payne, 606 F.2d 303, 203 USPQ 245 (CCPA 1979). See also In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986) (claimed and prior art compounds used in a method of treating depression would have been expected to have similar activity because the structural difference between the compounds involved a known bioisosteric replacement)”.
Further according to MPEP 2144.09 (I), “A prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. "An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties." In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979).”
In the instant case, both the compounds of the reference ‘499 patent and the instant compounds have utility as GLP-1 receptor agonists. Moreover, the compounds of the reference ‘499 patent have close structural similarity to the instant compound, differing only in the reference compound being a homolog (i.e., differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) OR the structural difference between the compounds involves a known bioisosteric replacement of a CH by N (piperidine versus piperazine), rendering them prima facie obvious.
The reference ‘499 patent does not teach the specific pharmaceutically acceptable salts of the instant claims.
Aspnes teaches 6-carboxylic acids of benzimidazoles or a pharmaceutically acceptable salt thereof, as GLP-1 R agonists (Abstract; Pg. 3, Ln. 23 - Pg. 5, Ln. 7). Aspnes teaches structurally related heterocyclic compounds differing in the size of the oxygen-containing ring fused to the benzene ring (Pg. 16, Lns. 15-17). Aspnes teaches suitable acid addition salts to include hydrochloride, … malate, … tartrate, tosylate, … (Pg. 24, Lns. 18-25). Aspnes teaches suitable base salts to include arginine, … meglumine, … potassium, sodium, 2-Amino-2-(hydroxymethyl)propane-1 ,3-diol (tris or tromethamine) salts (Pg. 24, Lns. 27-30). Aspnes teaches a method of preparing the pharmaceutically acceptable salts by reacting the compounds with the desired acid or base (Pg. 24, Lns. 34-36). Aspnes teaches a method of treating a disease for which an agonist of GLP-1 R is indicated, including prevention and/or treatment of diabetes (Pg. 20, Lns. 3-10).
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 claims of the reference ‘499 patent and Aspnes to have synthesized the specific pharmaceutically acceptable salts, say, hydrochloride, malate, tartrate, tosylate, arginine, meglumine, potassium, sodium and tromethamine, to arrive at the pharmaceutically acceptable salts of the instant claims with a reasonable expectation of success. It would have been prima facie obvious to arrive at the pharmaceutical compositions and methods of use thereof.
Therefore, claims 1-13 and 16-18 of the reference ‘499 patent in view of Aspnes render instant claims 1, 3, 21 and 38-40, prima facie obvious.
Thus, claims 1-13 and 16-18 of U.S. Patent No. 12,227,499 B2 and instant claims 1, 3, 21 and 38-40 are not patentably distinct.
This is a nonstatutory double patenting rejection.
Claims 1, 3, 21 and 38-40 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 7-8, 11-13 and 17-18 of U.S. Patent No. 12,459,937 B2 in view of Aspnes et al. (WO 2019/239319 A1, 19 December 2019, hereinafter Aspnes, in the IDS).
Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are drawn to compounds, wherein the compound is 2-(4-(S)-3-(4-chloro-2-fluorophenyl)-2,3-dihydrobenzofblf1,4]dioxan-5-yl)piperidin-1-yl)methyl)-1-((S)-oxetan-2-yl)methyl)-1H-benzo[d]imidazole-6-carboxylic acid.
The instant claims are drawn to a pharmaceutically acceptable salt of compound 2-(4-(S)-3-(4-chloro-2-fluorophenyl)-2,3-dihydrobenzofblf1,4]dioxan-5-yl)piperidin-1-yl)methyl)-1-((S)-oxetan-2-yl)methyl)-1H-benzo[d]imidazole-6-carboxylic acid, wherein the pharmaceutically acceptable salt is selected from a tromethamine salt, an ammonium salt, a potassium salt, an arginine salt, a sodium salt, a meglumine salt, an ethanolamine salt, a p-toluenesulfonate salt, a tartrate salt, a sulfate salt, a malate salt, and a hydrochloride salt, a method of preparation thereof, pharmaceutical compositions and methods of use thereof.
The claims of the reference ‘937 patent are drawn to a compound selected from the group consisting of a list that includes
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, or a pharmaceutically acceptable salt thereof. Claims 1-3 and 7-8 of the reference ‘937 patent anticipate the compound of the instant claims. Looking into the disclosure of the ‘937 patent for the utility of the compounds, the ‘937 patent teaches the compounds as GLP-1 receptor agonists (Col. 187, Ln. 40 - Col. 188, Ln. 52). The reference ‘937 patent does not teach the specific pharmaceutically acceptable salts of the instant claims.
Aspnes teaches 6-carboxylic acids of benzimidazoles or a pharmaceutically acceptable salt thereof, as GLP-1 R agonists (Abstract; Pg. 3, Ln. 23 - Pg. 5, Ln. 7). Aspnes teaches structurally related heterocyclic compounds differing in the size of the oxygen-containing ring fused to the benzene ring (Pg. 16, Lns. 15-17). Aspnes teaches suitable acid addition salts to include hydrochloride, … malate, … tartrate, tosylate, … (Pg. 24, Lns. 18-25). Aspnes teaches suitable base salts to include arginine, … meglumine, … potassium, sodium, 2-Amino-2-(hydroxymethyl)propane-1 ,3-diol (tris or tromethamine) salts (Pg. 24, Lns. 27-30). Aspnes teaches a method of preparing the pharmaceutically acceptable salts by reacting the compounds with the desired acid or base (Pg. 24, Lns. 34-36). Aspnes teaches a method of treating a disease for which an agonist of GLP-1 R is indicated, including prevention and/or treatment of diabetes (Pg. 20, Lns. 3-10).
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 claims of the reference ‘499 patent and Aspnes to have synthesized the specific pharmaceutically acceptable salts, say, hydrochloride, malate, tartrate, tosylate, arginine, meglumine, potassium, sodium and tromethamine, to arrive at the pharmaceutically acceptable salts of the instant claims with a reasonable expectation of success. It would have been prima facie obvious to arrive at the methods of use thereof.
Claims 11-13 and 17-18 of the reference ‘937 patent render obvious the pharmaceutical composition of the instant claims.
Therefore, claims 1-3, 7-8, 11-13 and 17-18 of the reference ‘937 patent in view of Aspnes render instant claims 1, 3, 21 and 38-40, prima facie obvious.
Thus, claims 1-3, 7-8, 11-13 and 17-18 of U.S. Patent No. 12,459,937 B2 and instant claims 1, 3, 21 and 38-40 are not patentably distinct.
This is a nonstatutory double patenting rejection.
Claims 1, 3, 21 and 38-40 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 32-53, 55-56 and 61-63 of co-pending Application No 19/012,024 in view of Aspnes et al. (WO 2019/239319 A1, 19 December 2019, hereinafter Aspnes, in the IDS).
Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are drawn to compounds, wherein the compound is 2-(4-(S)-3-(4-chloro-2-fluorophenyl)-2,3-dihydrobenzofblf1,4]dioxan-5-yl)piperidin-1-yl)methyl)-1-((S)-oxetan-2-yl)methyl)-1H-benzo[d]imidazole-6-carboxylic acid.
The instant claims are drawn to a pharmaceutically acceptable salt of compound 2-(4-(S)-3-(4-chloro-2-fluorophenyl)-2,3-dihydrobenzofblf1,4]dioxan-5-yl)piperidin-1-yl)methyl)-1-((S)-oxetan-2-yl)methyl)-1H-benzo[d]imidazole-6-carboxylic acid, wherein the pharmaceutically acceptable salt is selected from a tromethamine salt, an ammonium salt, a potassium salt, an arginine salt, a sodium salt, a meglumine salt, an ethanolamine salt, a p-toluenesulfonate salt, a tartrate salt, a sulfate salt, a malate salt, and a hydrochloride salt, a method of preparation thereof, pharmaceutical compositions and methods of use thereof.
The claims of the reference co-pending ‘024 application are drawn to a method of treating a disease, disorder, or condition in a subject, the method comprising administering to the subject a compound of general formula (IN), or a pharmaceutically acceptable salt thereof.
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Claims 53 and 55-56 of the reference co-pending ‘024 application anticipate the compound of the instant claims,
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, or a pharmaceutically acceptable salt thereof.
The reference co-pending ‘024 application does not teach the specific pharmaceutically acceptable salts of the instant claims.
Aspnes teaches 6-carboxylic acids of benzimidazoles or a pharmaceutically acceptable salt thereof, as GLP-1 R agonists (Abstract; Pg. 3, Ln. 23 - Pg. 5, Ln. 7). Aspnes teaches structurally related heterocyclic compounds differing in the size of the oxygen-containing ring fused to the benzene ring (Pg. 16, Lns. 15-17). Aspnes teaches suitable acid addition salts to include hydrochloride, … malate, … tartrate, tosylate, … (Pg. 24, Lns. 18-25). Aspnes teaches suitable base salts to include arginine, … meglumine, … potassium, sodium, 2-Amino-2-(hydroxymethyl)propane-1 ,3-diol (tris or tromethamine) salts (Pg. 24, Lns. 27-30). Aspnes teaches a method of preparing the pharmaceutically acceptable salts by reacting the compounds with the desired acid or base (Pg. 24, Lns. 34-36). Aspnes teaches a method of treating a disease for which an agonist of GLP-1 R is indicated, including prevention and/or treatment of diabetes (Pg. 20, Lns. 3-10).
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 claims of the reference ‘499 patent and Aspnes to have synthesized the specific pharmaceutically acceptable salts, say, hydrochloride, malate, tartrate, tosylate, arginine, meglumine, potassium, sodium and tromethamine, to arrive at the pharmaceutically acceptable salts of the instant claims with a reasonable expectation of success. It would have been prima facie obvious to arrive at the pharmaceutical compositions of the instant claims.
Claims 1 and 61-63 of the reference co-pending ‘024 application render obvious the method of treating a GLP-1 associated condition as in instant claims 38-39.
Therefore, claims 32-53, 55-56 and 61-63 of the reference co-pending ‘024 application in view of Aspnes render instant claims 1, 3, 21 and 38-40, prima facie obvious.
Thus, claims 32-53, 55-56 and 61-63 of the reference co-pending ‘024 application and instant claims 1, 3, 21 and 38-40 are not patentably distinct.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Allowable Subject Matter
Except for the 35 U.S.C. 112(b) rejection above, the crystal form salts of instant claims 5, 12 characterized by the X-ray powder diffraction patterns and crystal forms of instant claims 32-33 are free of prior art. Accordingly, the dependent claims 11, 26-29 and 34-37 drawn to a pharmaceutical composition, a method of preparation of the pharmaceutical composition thereof and methods of use thereof are also free of prior art.
Miscellaneous
The examiner would like to bring Applicant’s attention to the following:
An inventor’s oath or declaration signed by all the inventors is not present in the application file.
Conclusion
Claims 1, 3, 5, 11-12, 21, 26-29 and 32-40 are rejected.
No claims are allowed.
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/PADMAJA S RAO/Examiner, Art Unit 1627
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