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 .
Election/Restrictions
Applicant’s election without traverse of the species Compound 17
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, steroids, and sepsis in the reply filed on 27 August 2025 is acknowledged.
A search was performed for the claimed compound, with prior art retrieved. The search was expanded to encompass all species of Claim 1, with prior art retrieved (See STN Search Notes). The search was then stopped. The election of species requirement is hereby withdrawn.
Claims 1-7 and 15, submitted 27 August 2025, represent all claims currently under consideration.
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
The effective filing date is 16 April 2020.
Information Disclosure Statement
Two Information Disclosure Statements (IDSs), both submitted on 27 August 2025, are acknowledged and have been considered.
Claim Objections
Claim 1 is objected to because of the following informalities: There is an “and” before S-C1-C6, which should be before N(C1-C6 alkyl)2 in the description for the Markush group of variable R3. Appropriate correction is required.
Claim 3 is objected to because of the following informalities: “ARDS” is not defined prior to the first use of the abbreviation, and should be defined as “Acute Respiratory Distress Syndrome” prior to using the abbreviation. Appropriate correction is required.
Claim Rejections - 35 USC § 112(a)
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 1 and 4-7 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 the treatment of disorders associated with vascular hyperpermeability and/or conditions arising therefrom wherein TRPC6 is implicated, it does not reasonably provide enablement for all conditions associated with vascular hyperpermeability and/or conditions arising therefrom. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims. Consideration of the relevant factors sufficient to establish a prima facie case for lack of enablement is set forth below:
The nature of the invention and breadth of the claims:
The claims are directed towards a method of treating disorders associated with vascular hyperpermeability and/or conditions arising therefrom, comprising administering to a patient in need a therapeutically effective amount of a compound of Formula (I), which are inhibitors of TRP6C. The specification states that “vascular hyperpermeability contributes to many diseases, including… cancer” (Page 3). Thus, the claims are directed to a method which can be used to treat all forms of cancer by inhibiting TRP6C using the compounds of the invention.
The state of the prior art and the predictability or unpredictability of the art:
Yang (Oncotarget, 2017, 8:5123-5134) performed a study on TRPC6 inhibition for the treatment of non-small cell lung cancer. Studies indicate that TRPC6 is highly expressed in several types of cancer. Using the human NSCLC A549 cell line as a model, the authors found that inhibition or knockdown of TRPC6 channel inhibited A549 cell proliferation by arresting cell cycle. The data suggest that TRPC6 stimulates cell proliferation, and that TRPC6 inhibition attenuates cell proliferation and invasion (Abstract). However, as Yang states, TRP6C is highly expressed in several types of cancer, not all forms of cancer. The Human Protein Atlas (https://web.archive.org/web/20160804013702/https://www.proteinatlas.org/ENSG00000137672-TRPC6/cancer, 4 August 2016, TRPC6 Expression in Cancer) shows that while TRP6C is expressed in a variety of cancers, it is not expressed in all forms which were studied, and even within the same type of cancer, it is not ubiquitously expressed. Thus, not all cancers can be successfully treated by inhibition of TRP6C as not all forms of cancer express this channel, and there is currently no known treatment that can be used to treat all forms of cancer.
The relative skill of those in the art:
The artisan would generally have an advanced degree related to the treatment or study of various diseases including cancers; however, their high level of training and knowledge would not be sufficient to overcome the lack of understanding of how to use the claimed compounds to treat all forms of cancer, as not all forms of cancer are sensitive to inhibition of TRP6C.
The amount of direction or guidance presented and the presence or absence of working examples:
Example 1 (Page 39) shows that compounds of the invention reduced LPS-induced vascular leakage in a mouse model. Example 2 (Page 40) demonstrates the treatment of SARS-CoV-2 using the compounds of the invention. Thus, conditions such as pulmonary edema, sepsis, and SARS-CoV-2 are enabled using the compounds of the invention. The specification does not demonstrate the treatment of any forms of cancer using the compounds of the invention.
The quantity of experimentation necessary:
Considering the state of the art as described above, in particular with regards to the lack of a panacea for the treatment of cancer due to the heterogenous nature of the disease, and the high unpredictability of the art as evidenced therein, and the lack of guidance provided in the specification, one of ordinary skill in the art would be burdened with undue experimentation to practice the invention commensurate with the scope of the claims.
Claim Rejections - 35 USC § 112(b)
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.
Claim 2 is 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. Claim 2 is indefinite because the limitation “(ARDS), not infection-related” is unclear. It is unclear what ARDS refers to, and whether “not infection-related” refers to the condition. The Examiner suggests amending the claim to read “Acute Respiratory Distress Syndrome (ARDS) (not infection-related)” or similar to clarify that the claim is directed towards treating ARDS not related to an infection.
Claim 5 is 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. Claim 5 is indefinite due to the limitation “and the pharmaceutically acceptable salts thereof”. The claim as presently written is directed to individual compounds and the pharmaceutically acceptable salts thereof. The Examiner suggests replacing “and the pharmaceutically acceptable salts thereof” with “or a pharmaceutically acceptable salt thereof” to remedy the indefiniteness.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 3-7 and 15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5, and 8 of copending Application No. 18/700,748 (Amended Claims of 4 December 2024) (‘748) in view of Annane (Annals of Intensive Care, 2011 April 13; 1:7) and Remick (Infection and Immunity, 2005 May; 73(5):2751-2757).
Claim 1 of ‘748 is directed to a method for treating a patient with a systemic response to a bacterial or fungal infection, the method comprising administering to the patient a pharmaceutically effective amount of a compound of Formula (I)
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261
693
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wherein
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855
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824
847
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. Claim 5 of ‘748 is directed to the method of claim 1 wherein the compound is selected from the group consisting of several compounds which meet the limitations of the examined application and are identical to those of Claim 5, such as Compound 17
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. Claim 8 is directed to the method of claim 1 wherein the treatment is for a patient with bacterial sepsis, bacterial severe sepsis, bacterial septic shock, fungal sepsis, fungal severe sepsis, or fungal septic shock.
‘748 does not teach the co-administration of a second therapeutic such as steroid or IL-6 antibody for the treatment of these conditions.
Remick (Infection and Immunity, May 2005, 2751-2757) provides an overview of IL-6 in sepsis. Previous studies have suggested that IL-6 serves as both a marker and mediator for sepsis (Abstract). Studies have shown that antibody inhibition of IL-6 improved survival in a bacterium-derived sepsis model and antibodies to IL-6 will improve survival in sepsis if the correct dose is used (Introduction).
Annane (Annals of Intensive Care, 2011, 1:7) provides a review of the use of steroids in the treatment of sepsis. There is now ample evidence that the inability of the host to mount an appropriate hypothalamic-pituitary and adrenal axis response plays a major in overwhelming systemic inflammation during infections. Proinflammatory mediators released in the inflamed sites oppose to the anti-inflammatory response, an effect that may be reversed by exogenous corticosteroids. With sepsis, via nongenomic and genomic effects, corticosteroids restore cardiovascular homeostasis, terminate systemic and tissue inflammation, restore organ function, and prevent death. These effects of corticosteroids have been consistently found in animal studies and in most recent frequentist and Bayesian meta-analyses. Corticosteroids should be initiated only in patients with sepsis who require 0.5 μg/kg per minute or more of norepinephrine and should be continued for 5 to 7 days except in patients with poor hemodynamic response after 2 days of corticosteroids and with a cortisol increment of more than 250 nmol/L after a standard adrenocorticotropin hormone (ACTH) test. Hydrocortisone should be given at a daily dose of 200 mg and preferably combined to enteral fludrocortisone at a dose of 50 μg. Blood glucose levels should be kept below 150 mg/dL.
‘748, Remick, and Annane are considered analogous to the claimed invention as all are involved in the treatment of inflammatory diseases. Therefore, it would have been prima facie obvious to one of ordinary skill in the art the time of the effective filing date of the instant application to modify the treatment method of ‘748 to incorporate IL-6 antibodies or steroids as Remick and Annane demonstrate that these therapeutics are known in the art to be useful for the treatment of these conditions. Moreover, each of the claimed conditions to be treated are related to inflammation, and as such, it would be prima facie obvious to one of ordinary skill in the art to utilize these therapeutics, or any of the claimed therapeutics as these are known in the art to be useful for the treatment of these conditions. This combination is prima facie obvious combination of equivalents known for the same purpose (See MPEP § 2144.06 I). "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
This is a provisional nonstatutory double patenting rejection (Abstract).
Claims 1-7 and 15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 18 of U.S. Patent No. RE 49,699 (Patent Date: 17 October 2023) (‘699) in view of Wu (Molecular Immunology, Volume 64, Issue 1, March 2015, 18-25), Annane (Annals of Intensive Care, 2011 April 13; 1:7) and Remick (Infection and Immunity, 2005 May; 73(5):2751-2757).
Claim 1 of ‘699 is directed to a compound of Formula (I)
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wherein
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. Compounds of the invention include the compound 6-{1-[5-(4-Fluorophenoxy)-4-methoxypyridine-2-carbonyl]piperidin-4-yl}-pyridzin-3-amine (Column 195), which is identical to the compound elected in the examined application. Claim 18 claims a method for treating a disease or disorder that can be alleviated by TRPC6 inhibition, the method comprising administering a therapeutically effective amount of a compound of Claim 1 to a patient in need thereof, wherein the disease is selected from a group which includes idiopathic pulmonary fibrosis and acute respiratory distress syndrome.
‘699 fails to teach the treatment of sepsis, and use of a second therapeutic such as steroids or IL-6 antibodies.
The teachings of Annane and Remick are previously described and are fully incorporated into this rejection.
Wu studied the link between TRPC6 and sepsis in a rat model. Using the inhibitor SKF96365, they found that the rise of intracellular calcium in septic T lymphocytes was inhibited, and this suppresses the apoptotic ratio of septic T lymphocytes. The results suggest that CaSR activation promoted the expression of TRPC6 and enhanced T lymphocyte apoptosis through PLC-IP3 signaling pathway in sepsis (Abstract). The authors conclude by stating that inhibiting TRPC channel activity may be an effective way to help sepsis patients achieve better therapeutic outcomes.
‘699, Wu, Annane, and Remick are considered analogous to the claimed invention as all are involved in the treatment of inflammatory diseases. Therefore, it would have been prima facie obvious to one of ordinary skill in the art the time of the effective filing date of the instant application to use the compounds and methods of ‘699 to treat sepsis as Wu shows that TRPC6 is involved in the apoptosis of T-lymphocytes in sepsis, and states that inhibition of TRPC activity may be an effective way to help septic patients achieve better therapeutic outcomes, providing both a motivation and reasonable expectation of success in performing this modification. The use of the compounds and methods of ‘699 to treat sepsis is prima facie obvious use of a known technique to improve similar methods in the same way (See MPEP § 2143 I (C)); the compounds of ‘699 are inhibitors of TRPC6, and claim methods of treating conditions wherein TRPC6 is implicated, with Wu demonstrating a crucial role of TRPC6 in the pathology of sepsis.
Regarding Claims 6 and 7, it would have been prima facie obvious to one of ordinary skill in the art the time of the effective filing date of the instant application to modify the treatment method of ‘699 to incorporate IL-6 antibodies or steroids as Remick and Annane demonstrate that these therapeutics are known in the art to be useful for the treatment of these conditions. Moreover, each of the claimed conditions to be treated are related to inflammation, and as such, it would be prima facie obvious to one of ordinary skill in the art to utilize these therapeutics, or any of the claimed therapeutics as these are known in the art to be useful for the treatment of these conditions. This combination is prima facie obvious combination of equivalents known for the same purpose (See MPEP § 2144.06 I). "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
Claims 1-7 and 15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 8 of U.S. Patent No. 12,156,874 (Patent Date: 3 December 2024) (‘874) in view of Thornber (Chemical Society Reviews, Issue 4, 1979), Wu (Molecular Immunology, Volume 64, Issue 1, March 2015, 18-25), Annane (Annals of Intensive Care, 2011 April 13; 1:7) and Remick (Infection and Immunity, 2005 May; 73(5):2751-2757).
Claim 1 of ‘874 claims a compound of formula I
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wherein
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. Claim 8 is directed to specific compounds which are similar to those of the examined application such as
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. Claim 12 claims a method for treating a disease or disorder that can be alleviated by TRPC6 inhibition comprising administering a therapeutically effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt thereof.
‘874 does not teach a phenyl ring in the analogous variable R1 position, the treatment of sepsis, or a second therapeutic agent.
Thornber teaches the concept of bioisosterism, which is the concept wherein groups or molecules which have chemical and physical similarities produce broadly similar biological properties (Page 563). Table 1 (Page 564) lists the classical isosteres, and includes ring equivalents. Such ring equivalents include -CH=CH-, =CH-, =N-, and S. These atoms have similar electronic properties and as such, their replacement within a ring system is not expected to significantly alter the properties of that ring.
The teachings of Wu, Annane, and Remick are described previously and are fully incorporated into this rejection.
‘874, Thornber, Wu, Annane, and Remick are considered analogous to the claimed invention as all are involved in the study of therapeutic agents. Therefore, it would have been prima facie obvious to one of ordinary skill in the art the time of the effective filing date of the instant application to modify the compounds of ‘874 by replacing the pyridine ring system with a phenyl ring system, arriving at the compounds of the claimed invention, and further utilize these compounds in methods of treating sepsis. Thornber teaches that =N- and =CH- function as ring equivalents, and thus the artisan would not expect the properties of these compounds to be significantly altered by performing this substitution as due to the close chemical structure (See MPEP § 2144.09 I), as the compounds of ‘874 are TRPC6 inhibitors, similar to those of the examined application. It would have been prima facie obvious to one of ordinary skill in the art the time of the effective filing date of the instant application to use the compounds modified in view of Thornber and their methods of treatment to treat sepsis as Wu shows that TRPC6 is involved in the apoptosis of T-lymphocytes in sepsis, and states that inhibition of TRPC activity may be an effective way to help septic patients achieve better therapeutic outcomes, providing both a motivation and reasonable expectation of success in performing this modification. The use of the compounds and methods of ‘874 to treat sepsis is prima facie obvious use of a known technique to improve similar methods in the same way (See MPEP § 2143 I (C)); the compounds of ‘874 are inhibitors of TRPC6, and claim methods of treating conditions wherein TRPC6 is implicated, with Wu demonstrating a crucial role of TRPC6 in the pathology of sepsis.
Regarding Claims 6 and 7, it would have been prima facie obvious to one of ordinary skill in the art the time of the effective filing date of the instant application to modify the treatment method of ‘874 to incorporate IL-6 antibodies or steroids as Remick and Annane demonstrate that these therapeutics are known in the art to be useful for the treatment of these conditions. Moreover, each of the claimed conditions to be treated are related to inflammation, and as such, it would be prima facie obvious to one of ordinary skill in the art to utilize these therapeutics, or any of the claimed therapeutics as these are known in the art to be useful for the treatment of these conditions. This combination is prima facie obvious combination of equivalents known for the same purpose (See MPEP § 2144.06 I). "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
Claims 1-7 and 15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 17, and 19-20 of U.S. Patent No. 11,485,740 (Patent Date: 1 November 2022) (‘740) in view of Wu (Molecular Immunology, Volume 64, Issue 1, March 2015, 18-25), Annane (Annals of Intensive Care, 2011 April 13; 1:7) and Remick (Infection and Immunity, 2005 May; 73(5):2751-2757).
Claim 1 of ‘740 is directed to a compound of Formula (I)
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wherein
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. Claim 17 is directed to several specific compounds of Claim 1, many of which meet the limitations of the examined application and are identical to the compounds of examined claim 5, including Compound 36
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. Claim 19 is directed to a method of treating a disease or disorder that can be alleviated by TRPC6 inhibition comprising administering a therapeutically effective amount of a compound according to Claim 1. Claim 20 is directed to the method of claim 19 wherein the disorder is selected from diseases including sepsis, severe sepsis, septic shock, pulmonary disease, lung fibrosis, idiopathic pulmonary fibrosis, and acute respiratory distress syndrome.
‘740 does not teach the treatment of sepsis or use of a second therapeutic agent.
The teachings of Wu, Annane, and Remick are described previously and are fully incorporated into this rejection.
‘740, Wu, Annane, and Remick are considered analogous to the claimed invention as all are involved in the treatment of inflammatory diseases. Therefore, it would have been prima facie obvious to one of ordinary skill in the art the time of the effective filing date of the instant application to use the compounds and methods of ‘740 to treat sepsis as Wu shows that TRPC6 is involved in the apoptosis of T-lymphocytes in sepsis, and states that inhibition of TRPC activity may be an effective way to help septic patients achieve better therapeutic outcomes, providing both a motivation and reasonable expectation of success in performing this modification. The use of the compounds and methods of ‘740 to treat sepsis is prima facie obvious use of a known technique to improve similar methods in the same way (See MPEP § 2143 I (C)); the compounds of ‘740 are inhibitors of TRPC6, and claim methods of treating conditions wherein TRPC6 is implicated, with Wu demonstrating a crucial role of TRPC6 in the pathology of sepsis.
Regarding Claims 6 and 7, it would have been prima facie obvious to one of ordinary skill in the art the time of the effective filing date of the instant application to modify the treatment method of ‘740 to incorporate IL-6 antibodies or steroids as Remick and Annane demonstrate that these therapeutics are known in the art to be useful for the treatment of these conditions. Moreover, each of the claimed conditions to be treated are related to inflammation, and as such, it would be prima facie obvious to one of ordinary skill in the art to utilize these therapeutics, or any of the claimed therapeutics as these are known in the art to be useful for the treatment of these conditions. This combination is prima facie obvious combination of equivalents known for the same purpose (See MPEP § 2144.06 I). "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
Claims 1-7 and 15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 18 of U.S. Patent No. 10,800,757 (Patent Date: 13 October 2020) (‘757) in view of Wu (Molecular Immunology, Volume 64, Issue 1, March 2015, 18-25), Annane (Annals of Intensive Care, 2011 April 13; 1:7) and Remick (Infection and Immunity, 2005 May; 73(5):2751-2757).
Claim 1 of ‘757 is directed to a compound of Formula (I)
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. Compounds of the invention include the compound 6-{1-[5-(4-Fluorophenoxy)-4-methoxypyridine-2-carbonyl]piperidin-4-yl}-pyridzin-3-amine (Column 195), which is identical to the compound elected in the examined application. Claim 18 claims a method for treating a disease or disorder that can be alleviated by TRPC6 inhibition, the method comprising administering a therapeutically effective amount of a compound of Claim 1 to a patient in need thereof, wherein the disease is selected from a group which includes idiopathic pulmonary fibrosis and acute respiratory distress syndrome.
‘757 does not teach the treatment of sepsis or use of a second therapeutic agent.
The teachings of Wu, Annane, and Remick are described previously and are fully incorporated into this rejection.
‘757, Wu, Annane, and Remick are considered analogous to the claimed invention as all are involved in the treatment of inflammatory diseases. Therefore, it would have been prima facie obvious to one of ordinary skill in the art the time of the effective filing date of the instant application to use the compounds and methods of ‘757 to treat sepsis as Wu shows that TRPC6 is involved in the apoptosis of T-lymphocytes in sepsis, and states that inhibition of TRPC activity may be an effective way to help septic patients achieve better therapeutic outcomes, providing both a motivation and reasonable expectation of success in performing this modification. The use of the compounds and methods of ‘757 to treat sepsis is prima facie obvious use of a known technique to improve similar methods in the same way (See MPEP § 2143 I (C)); the compounds of ‘757 are inhibitors of TRPC6, and claim methods of treating conditions wherein TRPC6 is implicated, with Wu demonstrating a crucial role of TRPC6 in the pathology of sepsis.
Regarding Claims 6 and 7, it would have been prima facie obvious to one of ordinary skill in the art the time of the effective filing date of the instant application to modify the treatment method of ‘757 to incorporate IL-6 antibodies or steroids as Remick and Annane demonstrate that these therapeutics are known in the art to be useful for the treatment of these conditions. Moreover, each of the claimed conditions to be treated are related to inflammation, and as such, it would be prima facie obvious to one of ordinary skill in the art to utilize these therapeutics, or any of the claimed therapeutics as these are known in the art to be useful for the treatment of these conditions. This combination is prima facie obvious combination of equivalents known for the same purpose (See MPEP § 2144.06 I). "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
Claims 1-7 and 15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 11 of U.S. Patent No. 10,889,568 (Patent Date: 12 January 2021) (‘568) in view of Wu (Molecular Immunology, Volume 64, Issue 1, March 2015, 18-25), Annane (Annals of Intensive Care, 2011 April 13; 1:7) and Remick (Infection and Immunity, 2005 May; 73(5):2751-2757).
Claim 1 of ‘568 claims several specific compounds, including 4-(6-Amino-4-methyl-pyridazin-3-yl)-piperidin-l-yl]- [5-(4-fluoro-phenoxy)-4-methoxy-pyridin-2-yl]- methanone
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, which is identical to compound 29 of the examined application. Claim 11 claims a method of treating a disease or disorder that can be alleviated by TRP6C inhibition, comprising administering a therapeutically effective amount of a compound of Claim 1, wherein the disorder is selected from the group which includes idiopathic pulmonary fibrosis and acute respiratory syndrome.
‘568 does not teach the treatment of sepsis or use of a second therapeutic agent.
The teachings of Wu, Annane, and Remick are described previously and are fully incorporated into this rejection.
‘568, Wu, Annane, and Remick are considered analogous to the claimed invention as all are involved in the treatment of inflammatory diseases. Therefore, it would have been prima facie obvious to one of ordinary skill in the art the time of the effective filing date of the instant application to use the compounds and methods of ‘568 to treat sepsis as Wu shows that TRPC6 is involved in the apoptosis of T-lymphocytes in sepsis, and states that inhibition of TRPC activity may be an effective way to help septic patients achieve better therapeutic outcomes, providing both a motivation and reasonable expectation of success in performing this modification. The use of the compounds and methods of ‘568 to treat sepsis is prima facie obvious use of a known technique to improve similar methods in the same way (See MPEP § 2143 I (C)); the compounds of ‘568 are inhibitors of TRPC6, and claim methods of treating conditions wherein TRPC6 is implicated, with Wu demonstrating a crucial role of TRPC6 in the pathology of sepsis.
Regarding Claims 6 and 7, it would have been prima facie obvious to one of ordinary skill in the art the time of the effective filing date of the instant application to modify the treatment method of ‘568 to incorporate IL-6 antibodies or steroids as Remick and Annane demonstrate that these therapeutics are known in the art to be useful for the treatment of these conditions. Moreover, each of the claimed conditions to be treated are related to inflammation, and as such, it would be prima facie obvious to one of ordinary skill in the art to utilize these therapeutics, or any of the claimed therapeutics as these are known in the art to be useful for the treatment of these conditions. This combination is prima facie obvious combination of equivalents known for the same purpose (See MPEP § 2144.06 I). "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
Conclusion
Claims 1-7 and 15 are rejected.
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/P.M.R./Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625