DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . Claims 1-11 and 17 filed January 04, 2023 are currently pending.
Election/Restrictions
Applicant’s election without traverse of Group (I), claims 1-8 in the reply filed on 09/09/2025 is acknowledged.
Claims 9-11 and 17 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 09/09/2025.
Secondly, Applicant’s election without traverse of Compound A as the species of TRPV4 inhibitor and retinal vein occlusion as the species of retinal disease in the reply filed on 09/09/2025 is acknowledged.
Claim 7 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species of TRPV4 inhibitor, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 09/09/2025.
Priority
Acknowledgement is made of the national stage entry of PCT/JP2021/026829 filed 07/16/2021, which claims priority to U.S. Provisional 63052572 filed 07/16/2020.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 01/04/2023, 02/08/2023, 07/10/2024, 12/17/2024, 03/17/2025, 05/08/2025 and 08/12/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 112-Paragraph 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 directed to the method of claim 1, wherein the retinal disease is selected from the group consisting of hypertensive retinopathy and amaurosis, which are retinal diseases accompanied with blood flow disorder; selected from the group consisting of hereditary optic neuropathy, retinal detachment, choroidal metastases, choroidal melanoma and choroidal hemangioma, which are retinal diseases accompanied with cell disorder; or selected from the group consisting of retinal vein occlusion, retinal artery occlusion, wet age-related macular degeneration, retinitis pigmentosa, diabetic retinopathy, ischemic optic neuropathy, and glaucoma, which are retinal diseases accompanied with both blood flow disorder and cell disorder.
As recited in MPEP 2173.05(h), A Markush grouping is a closed group of alternatives, i.e., the selection is made from a group "consisting of" (rather than "comprising" or "including") the alternative members. Abbott Labs., 334 F.3d at 1280, 67 USPQ2d at 1196. If a Markush grouping requires a material selected from an open list of alternatives (e.g., selected from the group "comprising" or "consisting essentially of" the recited alternatives), the claim should generally be rejected under 35 U.S.C. 112(b) as indefinite because it is unclear what other alternatives are intended to be encompassed by the claim. See In re Kiely, 2022 USPQ2d 532 at 2* (Fed. Cir. 2022)
In the present case, the metes and bounds of claim 2 are unclear as there is an open list of alternative retinal disorders due to multiple Markush groups and it is unclear what other alternative retinal disorders are intended to be encompassed by the claim.
As recited in MPEP 2173.05 (a) Claim language may not be "ambiguous, vague, incoherent, opaque, or otherwise unclear in describing and defining the claimed invention." Packard, 751 F.3d at 1311. Applicants need not confine themselves to the terminology used in the prior art, but are required to make clear and precise the terms that are used to define the invention whereby the metes and bounds of the claimed invention can be ascertained. In the instant case, Applicant has failed to do so regarding the claimed genus of retinal disorder that lie within the boundaries of the claims.
For the purposes of examination, the examiner has interpreted the retinal disorders to be selected from the group consisting of hypertensive retinopathy, amaurosis, hereditary optic neuropathy, retinal detachment, choroidal metastases, choroidal melanoma, choroidal hemangioma, retinal vein occlusion, retinal artery occlusion, wet age-related macular degeneration, retinitis pigmentosa, diabetic retinopathy, ischemic optic neuropathy, and glaucoma. Subsequent examination is based on this interpretation.
Claim Rejections – Improper Markush Grouping
Claims 1-6 and 8 are rejected as being drawn to an improper Markush grouping.
Claims 1-6 and 8 are rejected on the judicially-created basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). The improper Markush grouping includes species of the claimed invention that do not share both a substantial structural feature and a common use that flows from the substantial structural feature. The instant claims do not share a common core chemical structure or single structural similarity. The claims are drawn to a method of treating or preventing retinal disease accompanied with blood flow disorder or cell disorder in a mammalian subject a therapeutically effective amount of an inhibitor of TRPV4. As shown in claims 5-6, inhibitors of TRPV4 may be any of a very large number of patentably distinct functional groups falling within Formulas (I)-(IV) or other compounds outside those formulas (RN-1734, RN1737, RN9893, PF-05214030). All of the genuses of TRPV4 inhibitors occupy patent classes C07C, C07D and A61K. The claims in their current form do not present any common chemical structure that can be attributed to the asserted utility of the compounds.
A Markush claim contains an “improper Markush grouping” if: (1) The species of the Markush group do not share a single structural similarity,” or (2) the species do not share a common use. Members of a Markush group share a "single structural similarity” when they belong to the same recognized physical or chemical class or to the same recognized physical or chemical class or to the same art-recognized class. Members of a Markush group share a common use when they are disclosed in the specification or known in the art to be functionally equivalent (see Federal Register, Vol. 76, No. 27, Wednesday, February 9, 2011, p. 7166, left and middle columns, bridging paragraph).
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The members of the improper Markush grouping do not share a substantial feature and/or a common use that flows from the substantial structural feature for the following reasons. As shown in Formulas (I)-(IV) above, the claimed TRPV4 inhibitors do not share a single structural similarity as they are composed of differing ring systems classified within classes C07C, C07D and A61K. See claims 5-6
For example, in claim 5, when the TRPV4 inhibitor is a substituted pyrimidinone of Formula (I), the compound is classified in C07D subclass 471/04 and A61K 31/519. Meanwhile, when the TPRV4 inhibitor is of Formula (II), the invention is classified in A61K 31/4184. When the TRPV4 inhibitor is a substituted quinoline of Formula (III), the invention is classified in class A61K subclass 31/4709, and when the TRPV4 inhibitor is a substituted pyrrole of Formula (IV), the invention is classified in class A61K subclass 31/4025.
The claims in their current form do not present any common chemical structure that can be attributed to the asserted utility of the compounds. See claim 5-6 which discloses the various species of Formulas (I)-(IV) above which do not present any common chemical structure.
The examiner suggests that this rejection may be overcome by amending the claims to the directed compounds that share a single structural similarity (e.g., Formula (I) OR alternatively Formula (II) OR alternatively Formula (III) OR alternatively Formula (IV). Many of the working examples in the specification correspond to this generic chemical Formula.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-2 and 8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ingber (WO2009/149239 published 12/10/2009).
Ingber (WO2009/149239 published 12/10/2009) teaches the method of treating the angiogenesis-mediated disorders macular degeneration and diabetic retinopathy in a subject in need comprising administering a therapeutically effective amount of an inhibitor of TRPV4 (claims 44, 52-54).
MPEP 2131 states that when a claimed compound is not specifically named in a reference, but instead it is necessary to select portions of teachings within the reference and combine them, e.g., select various substituents from a list of alternatives given for placement at specific sites on a generic chemical formula to arrive at a specific composition, anticipation can only be found if the classes of substituents are sufficiently limited or well delineated. Ex parte A, 17 USPQ2d 1716 (Bd. Pat. App. & Inter. 1990). If one of ordinary skill in the art is able to "at once envisage" the specific compound within the generic chemical formula, the compound is anticipated. One of ordinary skill in the art must be able to draw the structural formula or write the name of each of the compounds included in the generic formula before any of the compounds can be "at once envisaged." One may look to the preferred embodiments to determine which compounds can be anticipated. In re Petering, 301 F.2d 676, 133 USPQ 275 (CCPA 1962). In In re Petering, the prior art disclosed a generic chemical formula "wherein X, Y, Z, P, and R'- represent either hydrogen or alkyl radicals, R a side chain containing an OH group." The court held that this formula, without more, could not anticipate a claim to 7-methyl-9-[d, l'-ribityl]-isoalloxazine because the generic formula encompassed a vast number and perhaps even an infinite number of compounds. However, the reference also disclosed preferred substituents for X, Y, Z, P, R, and R' as follows: where X, P, and R' are hydrogen, where Y and Z may be hydrogen or methyl, and where R is one of eight specific isoalloxazines. The court determined that this more limited generic class consisted of about 20 compounds. The limited number of compounds covered by the preferred formula in combination with the fact that the number of substituents was low at each site, the ring positions were limited, and there was a large unchanging structural nucleus, resulted in a finding that the reference sufficiently described "each of the various permutations here involved as fully as if he had drawn each structural formula or had written each name." The claimed compound was 1 of these 20 compounds. Therefore, the reference "described" the claimed compound and the reference anticipated the claims
In the present case and as recited by Ingber above, macular degeneration and diabetic retinopathy are two of twelve delineated disorders that are effectively treated with the administration of an inhibitor of TRPV4. Accordingly, said skilled artisan is able to at once envisage the treatment of angiogenesis-mediated disorders macular degeneration and diabetic retinopathy in a subject in need comprising administering a therapeutically effective amount of an inhibitor of TRPV4. Regarding claim 8, Ingber teaches that said TRPV4 inhibitors are administered with an anti-angiogenic agent (claims 54).
Claim(s) 1-3, 8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Krizaj (US2017/0065602 published 03/09/2017).
Krizaj (US2017/0065602 published 03/09/2017) teaches the method of treating wet age-related macular degeneration in a subject in need comprising administering a therapeutically effective amount of an inhibitor of TRPV4 (claims 1, 15, 17-23).
MPEP 2131 states that when a claimed compound is not specifically named in a reference, but instead it is necessary to select portions of teachings within the reference and combine them, e.g., select various substituents from a list of alternatives given for placement at specific sites on a generic chemical formula to arrive at a specific composition, anticipation can only be found if the classes of substituents are sufficiently limited or well delineated. Ex parte A, 17 USPQ2d 1716 (Bd. Pat. App. & Inter. 1990). If one of ordinary skill in the art is able to "at once envisage" the specific compound within the generic chemical formula, the compound is anticipated. One of ordinary skill in the art must be able to draw the structural formula or write the name of each of the compounds included in the generic formula before any of the compounds can be "at once envisaged." One may look to the preferred embodiments to determine which compounds can be anticipated. In re Petering, 301 F.2d 676, 133 USPQ 275 (CCPA 1962). In In re Petering, the prior art disclosed a generic chemical formula "wherein X, Y, Z, P, and R'- represent either hydrogen or alkyl radicals, R a side chain containing an OH group." The court held that this formula, without more, could not anticipate a claim to 7-methyl-9-[d, l'-ribityl]-isoalloxazine because the generic formula encompassed a vast number and perhaps even an infinite number of compounds. However, the reference also disclosed preferred substituents for X, Y, Z, P, R, and R' as follows: where X, P, and R' are hydrogen, where Y and Z may be hydrogen or methyl, and where R is one of eight specific isoalloxazines. The court determined that this more limited generic class consisted of about 20 compounds. The limited number of compounds covered by the preferred formula in combination with the fact that the number of substituents was low at each site, the ring positions were limited, and there was a large unchanging structural nucleus, resulted in a finding that the reference sufficiently described "each of the various permutations here involved as fully as if he had drawn each structural formula or had written each name." The claimed compound was 1 of these 20 compounds. Therefore, the reference "described" the claimed compound and the reference anticipated the claims.
In the present case and as recited by Krizaj above, wet age-related macular degeneration and diabetic retinopathy are two of twelve delineated disorders that are effectively treated with the administration of an inhibitor of TRPV4. Accordingly, said skilled artisan is able to at once envisage the treatment of the proliferative retinopathy wet age-related macular degeneration and diabetic retinopathy in a subject in need comprising administering a therapeutically effective amount of an inhibitor of TRPV4.
Regarding claim 8, administration of said inhibitor of TRPV4 in combination with an anti-inflammatory agent is embraced within the methodology of Krizaj (claims 1, 15, 17-23).
Claim(s) 1-6, 8 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Behm (WO2021/170811 published 09/02/2021 with priority to U.S. Provisional Application 62982110 filed 02/27/2020) as evidenced by Rhoades (Taiwan J. Ophthalmol. Vol. 7 pages 70-76 published 2017).
Behm teaches treating wet-age related macular degeneration and macular edema following a retinal vein occlusion in a subject in need comprising administering a therapeutically effective amount of the art-recognized TRPV4 inhibitor 1-(((5S,7S)-3-(5-(2-hydroxypropan-2-yl)pyrazin-2-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile (abstract, page 25 lines 25-30, page 26 lines 30-35, claims 1-4, 7). As evidenced by Rhoades (Taiwan J. Ophthalmol. Vol. 7 pages 70-76 published 2017) the pathogenesis of central retinal vein occlusion (CRVO) is believed to involve vascular endothelial damage and compression of the retinal vein leading to thrombus formation. This leads to increased retinal capillary pressure, which causes transudation into the extracellular space and macular edema (page 70).
As such, the examiner has interpreted that said patient comprising “macular edema following a retinal vein occlusion” comprises both macular edema and a central retinal vein occlusion, wherein the vein in the retina is blocked, resulting in the complication of fluid buildup in the macula and yielding the disclosed macular edema.
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Regarding claim 5, the art-recognized TRPV4 inhibitor of Behm reads on the claimed limitation of Formula (II) as follows: R1 is C1-C3 alkyl; R2 is CN, A is (CH2)n-Het wherein n is 0, Het is pyrazine substituted by C1-C5 alkyl further substituted by OH. Behm teaches that intravitreal administration of the TRPV4 blocker at a dose of 15 mg/kg is efficacious at blocking retinal vascular leakage in an afflicted patient (pages 43-46).
Regarding claim 6, the administered 1-(((5S,7S)-3-(5-(2-hydroxypropan-2-yl)pyrazin-2-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile of Behm reads on GSK2798745 (page 16, lines 20-35, page 25 lines 25-30, page 26 lines 30-35).
Regarding claim 8, Behm teaches administering the TRPV4 inhibitor in combination with an additional therapeutic agent (claims 1-4, 7).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 1-6 and 8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Behm (WO2021/170811 published 09/02/2021 with priority to U.S. Provisional Application 62982110 filed 02/27/2020) as evidenced by Rhoades (Taiwan J. Ophthalmol. Vol. 7 pages 70-76 published 2017).
Behm teaches treating wet-age related macular degeneration and macular edema following a retinal vein occlusion in a subject in need comprising administering a therapeutically effective amount of the art-recognized TRPV4 inhibitor 1-(((5S,7S)-3-(5-(2-hydroxypropan-2-yl)pyrazin-2-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile (abstract, page 25 lines 25-30, page 26 lines 30-35, claims 1-4, 7). As evidenced by Rhoades (Taiwan J. Ophthalmol. Vol. 7 pages 70-76 published 2017) the pathogenesis of central retinal vein occlusion (CRVO) is believed to involve vascular endothelial damage and compression of the retinal vein leading to thrombus formation. This leads to increased retinal capillary pressure, which causes transudation into the extracellular space and macular edema (page 70).
As such, the examiner has interpreted that said patient comprising “macular edema following a retinal vein occlusion” comprises both macular edema and a central retinal vein occlusion, wherein the vein in the retina is blocked, resulting in the complication of fluid buildup in the macula and yielding the disclosed macular edema.
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Regarding claim 5, the art-recognized TRPV4 inhibitor of Behm reads on the claimed limitation of Formula (II) as follows: R1 is C1-C3 alkyl; R2 is CN, A is (CH2)n-Het wherein n is 0, Het is pyrazine substituted by C1-C5 alkyl further substituted by OH. Behm teaches that intravitreal administration of the TRPV4 blocker at a dose of 15 mg/kg is efficacious at blocking retinal vascular leakage in an afflicted patient (pages 43-46).
Regarding claim 6, the administered 1-(((5S,7S)-3-(5-(2-hydroxypropan-2-yl)pyrazin-2-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile of Behm reads on GSK2798745 (page 16, lines 20-35, page 25 lines 25-30, page 26 lines 30-35). Regarding claim 8, Behm teaches administering the TRPV4 inhibitor in combination with an additional therapeutic agent (claims 1-4, 7).
Therefore, one of ordinary skill in the art of treating retinal vein occlusion in a subject in need, said skilled artisan would have found it prima facie obvious to select the art-recognized TRPV4 inhibitor 1-(((5S,7S)-3-(5-(2-hydroxypropan-2-yl)pyrazin-2-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile and administer said TPRV4 inhibitor to treat the retinal disorder in the afflicted subject in view of Behm.
Considering Behm teaches that the art-recognized TRPV4 inhibitor 1-(((5S,7S)-3-(5-(2-hydroxypropan-2-yl)pyrazin-2-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile is efficacious at treating “macular edema following a retinal vein occlusion” which, as evidenced by Rhoades above comprises both macular edema and a central retinal vein occlusion, wherein the vein in the retina is blocked, resulting in the complication of fluid buildup in the macula and yielding the disclosed macular edema, said skilled artisan would have readily predicted that administration of the TRPV4 inhibitor would have treated both the central retinal vein occlusion and macular edema in the afflicted patient.
Claims 1-6 and 8 are rejected under 35 U.S.C. 103 as being obvious over the combination of Shishido (US2023/0339934 published 10/26/2023 with priority to U.S. Provisional Application 63017891 filed 04/30/2020) and Behm (WO2021/170811 published 09/02/2021 with priority to U.S. Provisional Application 62982110 filed 02/27/2020) as evidenced by Rhoades (Taiwan J. Ophthalmol. Vol. 7 pages 70-76 published 2017).
The applied reference has a common assignee (RaQualia) with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
Shishido (US2023/0339934 published 10/26/2023 with priority to U.S. Provisional Application 63017891 filed 04/30/2020) teaches TRPV4 inhibitors (title, abstract). Shishido teaches that Example 2-33 is a potent inhibitor of TRPV4 ([2462], Table 95). Example 2-33 corresponds to the following structural elements of Formula (I) shown below: R1 and R2 come together to form a C3 membered ring, Ar1 is phenyl r is 2, s is 1, X is CR5R6 wherein R5 is OH and R6 is H, Ar2 is 3-chlorophenyl ([2257]-[2261]).
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The difference between the present claims and that of Shishido is that Shishido does not specifically teach treating retinal vein occlusion in a subject in need comprising administering a therapeutically effective amount of the TPRV4 inhibitor.
Behm teaches treating wet-age related macular degeneration and macular edema following a retinal vein occlusion in a subject in need comprising administering a therapeutically effective amount of the art-recognized TRPV4 inhibitor 1-(((5S,7S)-3-(5-(2-hydroxypropan-2-yl)pyrazin-2-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile (abstract, page 25 lines 25-30, page 26 lines 30-35, claims 1-4, 7). As evidenced by Rhoades (Taiwan J. Ophthalmol. Vol. 7 pages 70-76 published 2017) the pathogenesis of central retinal vein occlusion (CRVO) is believed to involve vascular endothelial damage and compression of the retinal vein leading to thrombus formation. This leads to increased retinal capillary pressure, which causes transudation into the extracellular space and macular edema (page 70).
As such, the examiner has interpreted that said patient comprising “macular edema following a retinal vein occlusion” comprises both macular edema and a central retinal vein occlusion, wherein the vein in the retina is blocked, resulting in the complication of fluid buildup in the macula and yielding the disclosed macular edema.
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Regarding claim 5, the art-recognized TRPV4 inhibitor of Behm reads on the claimed limitation of Formula (II) as follows: R1 is C1-C3 alkyl; R2 is CN, A is (CH2)n-Het wherein n is 0, Het is pyrazine substituted by C1-C5 alkyl further substituted by OH. Behm teaches that intravitreal administration of the TRPV4 blocker at a dose of 15 mg/kg is efficacious at blocking retinal vascular leakage in an afflicted patient (pages 43-46).
Therefore, one of ordinary skill in the art prior to the time of the invention, knowing that Example 2-33 is a potent inhibitor of TRPV4 as taught by Shishido,
said skilled artisan would have found it prima facie obvious to administer said TPRV4 inhibitor to treat a patient comprising a retinal vein occlusion in view of Behm above, arriving at the presently claimed methodology with a reasonable expectation of success.
MPEP 2143 provides rationale for a conclusion of obviousness including (A): Combining prior art elements according to known methods to obtain predictable results;
In the present case, administration of the art-recognized TRPV4 inhibitor 1-(((5S,7S)-3-(5-(2-hydroxypropan-2-yl)pyrazin-2-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile was taught by Behm as an efficacious strategy to treat patients comprising “macular edema following a retinal vein occlusion” which embraces both macular edema and a central retinal vein occlusion. Accordingly, said skilled artisan would have readily predicted that substitution of the art-recognized TRPV4 inhibitor in the therapeutic regimen of Behm, for another TRPV4 inhibitor, such as Example 2-33 of Shishido, the resulting TRPV4 inhibitory regimen would effectively treat macular edema and a retinal vein occlusion in the afflicted patient.
Conclusion
In view of the rejections set forth above, no claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GEORGE W KOSTURKO whose telephone number is (571)270-5903. The examiner can normally be reached M-F 9:00-5:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, CLINTON A BROOKS can be reached at 571-270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/GEORGE W KOSTURKO/Examiner, Art Unit 1621