DETAILED ACTION
Status of Application
The response filed 11/06/2025 has been received, entered and carefully considered. The response affects the instant application accordingly:
Claims 1-3 have been amended.
Claim 10-15 has been cancelled.
Applicant had previously elected choroidal neovascularization as the species genera and with the further election of the specific condition of age related macular degeneration for the examination.
Claims 1-9, 16-18 are pending.
Claims 1-9, 16-18 are present for examination at this time.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
All grounds not addressed in the action are withdrawn or moot as a result of amendment.
New grounds of rejection are set forth in the current office action as a result of amendment.
New Grounds of Rejection
Due to the amendment of the claims the new grounds of rejection are applied:
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.
Claims 1-6, 16-18 are rejected under 35 U.S.C. 103 as being unpatentable over Moon et al. (KR101821593) in view of Beringer et al. (Ophthalmic Preparation -Buffer and pH, Additives).
Rejection:
Moon et al. teaches treating eye conditions including age-related macular degeneration with a pyrazole based compound as an active ingredient that is Formula I
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3-phenyl-4-propyl-1-(pyridin-2-yl) -1H-pyrazol-5-ol (APX-B, or 3-phenyl-4-n-propyl-1-(pyridin-2-yl) -1H-pyrazol-5-ol) and its hydrochloride salt
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3-phenyl-4-propyl-1-(pyridin-2-yl)-1H-pyrazole-5-ol hydrochloride (APX-115). The active is from 0.01-10% of the pharmaceutical composition, and the composition can contain various excipients including buffers/pH regulators and solubilizers; and can be in various formulations like solution/eyedrops (claims 1-7, 9-10; [1, 3, 8, 11-18, 20-24, 29, 35-38, 41-42,44-48, 51, 56-70]). Moon et al. also exemplifies treating an animal model for age-related macular degeneration with APX-115 (Example 8 [87-89], see full document specifically areas cited).
While Moon et al. does not recite the exact claimed values for instant claim 2-3, they are embraced and it is prima facie obvious to optimize within the taught range for the amount of the active and attain the instant claimed values and a means of attaining the desired therapeutic profile with a reasonable expectation of success absent evidence of criticality for the claimed values.
Moon et al. does not expressly recite the pH of the composition for the treatment or the types of solubilizers, but does teach the treatment of age-related macular degeneration with the compound (i.e. APX-115) in formulations like eyedrop with solubilizers and buffers/pH regulators.
Beringer et al. teaches that ophthalmic formulations should ideally be formulated to a pH of 7.4 which is the equivalent to the tear fluid (Buffers and pH 1st paragraph), and that common additives like surfactants like polysorbate 80 are used to aid in solubilization and stabilize drugs (polysorbate 80 is a polyoxyethylene sorbitan fatty acid ester, see solubilizers, Additives 4th paragraph).
Wherein it would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to formulate the pH of the composition applied to the eye be about 7.4 and for the solubilizers to be surfactants like polysorbate 80 as suggested by Beringer et al. and produce the claimed invention; as it is prima facie obvious to formulate the pH of the composition administered to be at the ideal pH with a reasonable expectation of success. It is also prima facie obvious to incorporate known solubilizers like polysorbates such as polysorbate 80 (a polyoxyethylene sorbitan fatty acid ester) for their known purpose with a reasonable expectation of success.
Response to Arguments:
Applicant's arguments filed 11/06/2025 are centered on the assertion that Moon et al. and Beringer et al.- individually or in combination - fail to disclose, teach or suggest the claimed method as amended in the independent claims; that conventional methods for treating posterior ocular diseases typically involves intravitreal injection and in contrast the present invention utilizes an eyedrop-eliminating the need for intraocular injection, the assertion that the eyedrop formulations in Table 8 (Examples 1, 3, 10, 11, 13, 14, 16, 34) have greater concentration of the active in the vitreous when the comparative formulation are 19 times lower being outside the pH range of 3.5-8.5; that while Moon et al. cites the claimed compound to be in an eyedrop it does not disclose or suggest improvement in drug delivery to the posterior segment by controlling the pH and that Beringer et al. fails to cure the deficiency; and that while Beringer et al. teaches that ophthalmic formulations should ideally be adjusted to a pH of 7.4 where the inclusion of surfactant and additives may be used to enhance drug stability it does not disclose or suggest a correlation between pH and the active to effectively reach the posterior of the eye.
This has been fully considered but are not persuasive. Applicant’s assertion that Moon et al. or Beringer et al. individually or in combination does not teach or disclose the claimed method is not persuasive as addressed by the rejection above. Moon et al teaches treating eye conditions including age-related macular degeneration with the claimed compound from 0.01-10% in the pharmaceutical composition like eyedrops, and can contain various excipients including buffers/pH regulators and solubilizers; wherein it is prima facie obvious to formulate the pH of the eye composition applied to be about 7.4 and for the solubilizers to be surfactants like polysorbate 80 as conventionally known as established by Beringer et al. with a reasonable expectation of success.
As for the assertion that Table 8 demonstrates that the eyedrop has greater concentration of the active in the vitreous in the pH range of 3.5-8.5 than the comparative formulation and that Moon et al. and Beringer et al. does not disclose or suggest a correlation between pH and the active to effectively reach the posterior of the eye to improve drug delivery to the posterior of the eye; this is fully considered but not persuasive. The formulations in Table 8 are not commensurate in scope with the instant claims, and contrary to Applicant’s assertion - Moon et al. expressly teaches treating age-related macular degeneration with the administration of the active with eyedrops – wherein the active is taught to treat the posterior segment of the eye with eyedrop administration wherein it is effective to address/reach the posterior segment of the eye, along with the inclusion of buffers and solubilizers.
As for the argument that Moon et al. and Beringer et al. do not disclose or suggest a correlation between pH and the active to effectively reach the posterior of the eye, this is not persuasive as the Examiner has a different reason for combining than the Applicant and the fact that Applicant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious.
Accordingly, the rejection stands.
Claims 7-9 are rejected under 35 U.S.C. 103 as being unpatentable over Moon et al. (KR101821593) in view of Beringer et al. (Ophthalmic Preparation -Buffer and pH, Additives) as applied to claims 1-6, 16-18 above, further in view of Rowe (Polyoxyethylene Sorbitan Fatty Acid Esters).
Rejection:
The teachings of Moon et al. in view of Beringer et al. are addressed above.
Moon et al. in view of Beringer et al. does not expressly teach the amount of solubilizer but does teach the inclusion of solubilizers/surfactants like polysorbates.
Rowe et al. teaches that polysorbates are known solubilizers/surfactants which are conventionally used in ranges like 1-15% of a formulation (Table IV, Section 6).
Wherein it would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to formulate the solubilizer/surfactant like polysorbates from 1-15% as suggested by Rowe et al. and produce the claimed invention; as it is prima facie obvious to formulated the solubilizer like polysorbate in their known range with a reasonable expectation of success.
Response to Arguments:
Applicant's arguments are directed to Moon et al. and Beringer et al. which are addressed above.
Accordingly, the rejection stands.
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 1-6, 16-18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 4-8 of U.S. Patent No. 11174240 in view of Moon et al. (KR101821593) and of Beringer et al. (Ophthalmic Preparation -Buffer and pH, Additives).
The patented claims 4-5 are directed a method of treating diseases including age-related macular degenerations with the administration of a crystalline
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to a patient in need thereof. Patented claims 6-7 are directed to a pharmaceutical composition comprising crystalline
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with additives including water, mineral oil (solvent/solubilizer), calcium phosphate (a buffer), and mixtures thereof; and in forms like an eyedrop and injection/solution.
While the patented claims to the method of treatment do not recite the additives and the patented claims to the composition does not recited the condition to be treated or the amount of active in the composition; Moon et al. teaches that this compound can be from 0.01-10% in a composition comprising with solubilizers and buffers in forms like eyedrops and known to be useful for the treatment of age-related macular degeneration, and Beringer et al. teaches that ophthalmic formulations should ideally be formulated at a pH equivalent to the tear fluid of 7.4 (Buffers and pH 1st paragraph) to minimize irritation, and that common additives include mineral oil and surfactants like polysorbate 80 (a polyoxyethylene sorbitan fatty acid ester) which are used to aid in solubilization and stabilize drugs (solubilizers, Additives 4th paragraph).
Wherein it would be prima facie obvious to use the patented composition for treating conditions it is known to be useful for, and it is also prima facie obvious for the patented claims for the method with the drug to incorporate the drug in formulations with additives like solubilizers and pH regulators/buffers that are taught for administrating the drug for the recited treatment with a reasonable expectation of success; and to formulate the pH at the ideal 7.4 in combination with known additives like polysorbate (a polyoxyethylene sorbitan fatty acid ester) with a reasonable expectation of success. It would also be prima facie obvious to optimize within the taught range for the amount of the active and attain the instant claimed values and a means of attaining the desired therapeutic profile with a reasonable expectation of success absent evidence of criticality for the claimed values.
Response to Arguments:
Applicant's arguments center on the assertion that the patented claims do not recite the inclusion of the recited solubilizing agents. This is fully considered but not persuasive as Applicant’s argument is to the patented claims only and not to the rejection as a whole and the obviousness with the patented claims in combination with Moon et al. and Beringer et al.
Accordingly, the rejection stands.
Claims 7-9 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 4-8 of U.S. Patent No. 11174240 in view of Moon et al. (KR101821593) and of Beringer et al. (Ophthalmic Preparation -Buffer and pH, Additives) as applied to claims 1-6, 16-18 above, further in view of Rowe (Polyoxyethylene Sorbitan Fatty Acid Esters).
The teachings of the patented claims in view of Moon et al. and Beringer et al. are addressed above.
The patented claims in view of Moon et al. and Beringer et al. do not expressly teach the amount of solubilizer but does teach the inclusion of solubilizers/surfactants like polysorbates.
Rowe et al. teaches that polysorbates are known solubilizers/surfactants/wetting agents which are conventionally used in ranges like 1-15% of a formulation (Table IV, Section 6).
Wherein it would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to formulate the solubilizer/surfactant like polysorbates from 1-15% as suggested by Rowe et al. and produce the claimed invention; as it is prima facie obvious to have the solubilizer/polysorbate in their known useful range with a reasonable expectation of success.
Response to Arguments:
Applicant's arguments are directed to the patented claims (in view of Moon et al. and Beringer et al.) which is addressed above.
Accordingly, the rejection stands.
Claims 1-6, 16-18 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10, 15-16 of copending Application No. 17614705 (reference application) in view of Moon et al. (KR101821593) and of Beringer et al. (Ophthalmic Preparation -Buffer and pH, Additives).
Although the claims at issue are not identical, they are not patentably distinct from each other because copending claim 16 is directed a method of treating eye diseases with the administration of a compound of formula 1 which includes.
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and a biodegradable polymer. Copending claims 1-15 are directed to a pharmaceutical composition comprising a compound of formula 1 which include
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with a biodegradable polymer (copending claims 6 can be as low as 10%, copending clam 7 recites an intended use for age-related macular degeneration).
While the copending claim to the method of treatment do not recite the additives and the copending claims to the composition does not recite the condition to be treated comprising the additives nor the amount of active in the composition administered; Moon et al. teaches that a composition comprising the compound of this formula including
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to be from 0.01-10% in combination with solubilizers and buffers in forms like eyedrops and to be useful for the treatment of age-related macular degeneration; and Beringer et al. teaches that ophthalmic formulations should ideally be formulate to a pH of 7.4 which is equivalent to the tear fluid (Buffers and pH 1st paragraph), and that common additives include surfactants like polysorbate 80 which are used to aid in solubilization and stabilize drugs(solubilizers, Additives 4th paragraph).
Wherein it would be prima facie obvious to use the copending composition for treating conditions it is known to be useful for, and it is also prima facie obvious for the copending claim for the method with the drug to incorporate the drug in formulations with additives like solubilizers and pH regulators/buffers that are taught for administrating the drug for the recited treatment with a reasonable expectation of success; and to formulate the composition to the ideal pH with other known additives like polysorbate with a reasonable expectation of success. It would also be prima facie obvious to optimize within the taught range for the amount of the active and attain the instant claimed values and a means of attaining the desired therapeutic profile with a reasonable expectation of success absent evidence of criticality for the claimed values.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments:
Applicant's arguments center on the assertion that the patented claims do not recite the inclusion of the recited solubilizing agents. This is fully considered but not persuasive as Applicant’s argument is to the patented claims only and not to the rejection as a whole and the obviousness with the patented claims in combination with Moon et al. and Beringer et al.
Accordingly, the rejection stands.
Claims 7-6 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10, 15-16 of copending Application No. 17614705 (reference application) in view of Moon et al. (KR101821593) and of Beringer et al. (Ophthalmic Preparation -Buffer and pH, Additives) as applied to claims 1-6, 16-18 above, further in view of Rowe (Polyoxyethylene Sorbitan Fatty Acid Esters).
The teachings of the copending claims in view of Moon et al. and Beringer et al. are addressed above.
The copending claims in view of Moon et al. and Beringer et al. do not expressly teach the amount of solubilizer but does teach the inclusion of solubilizers/surfactants like polysorbates.
Rowe et al. teaches that polysorbates are known solubilizers/surfactants/wetting agents which are conventionally used in ranges like 1-15% of a formulation (Table IV, Section 6).
Wherein it would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to formulate the solubilizer/surfactant like polysorbates from 1-15% as suggested by Rowe et al. and produce the claimed invention; as it is prima facie obvious to formulated the solubilizer like polysorbate in their known range with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments:
Applicant's arguments are directed to the patented claims (in view of Moon et al. and Beringer et al.) which is addressed above.
Accordingly, the rejection stands.
Conclusion
Claims 1-9, 16-18 are rejected.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GIGI GEORGIANA HUANG whose telephone number is (571)272-9073. The examiner can normally be reached Monday-Thursday 9:00-5:00pm.
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/GIGI G HUANG/Primary Examiner, Art Unit 1613