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 .
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.
Election/Restriction
Applicant’s election in the reply filed on 16 April 2026, is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Applicants’ provided compliant species elections of:
“choroidal neovascularization (CNV)” as the species of “eye disease”; and
“monothioglycerol” as species of “antioxidant”.
These elected species have prior art. Therefore, per Markush search practice, the Markush search will not be extended unnecessarily to additional species in this Office Action.
All claims read on the elected species.
Current Status of 18/728,964
This Office Action is responsive to the amended claims of 16 April 2026.
Claims 1-8, 11, and 14-22 have been examined on the merits. Claims 1, 3, and 11 are original. Claims 2, 4-8, and 14-22 are previously presented.
Priority
The effective filing date is 23 March 2022.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 12 February 2025; 7 November 2024; 20 October 2023; and 22 September 2023, are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Rejections - 35 USC § 112
The following is a quotation of 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 1-8, 11, and 14-22 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification and/or prior art, while being enabling for treating choroidal neovascularization (CNV), and the diseases of instant claim 22, does not reasonably provide enablement for treating or preventing the undefined scope of diseases of instant claims 1, 3, and 11 and the dependent claims thereof, with the instant formula 1, or pharmaceutically acceptable salts thereof. Furthermore, the prior art and/or Specification do not provide enablement for preventing the specific diseases of instant claim 22. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
The Wands Factors used in an (scope of) enablement rejection include (per MPEP 2164.01(a)):
1. The breadth of the claims:
The broadest reasonable interpretation (BRI) of instant claims 1, 3, and 11 are drawn to a method or composition to treat or prevent any eye disease with the pharmaceutical formulation comprising instant formula 1 (since the independent claims 1, 3, and 11 do not define the scope of eye diseases to be treated and/or prevented). There are some dependent claims that further define “eye disease” to a defined list of alternative species, many of which can be treated—but not prevented.
2. The Nature of the Invention:
The invention belongs to medicinals, more specifically, the administration of pharmaceutical formulations comprising instant formula 1 to treat or prevent eye diseases.
The BRI of instant claims 1, 3, and 11 do not define the scope of diseases to be treated or prevented.
3. The state of the prior art:
A review of the prior art reference MOON (KR 101821593 B1, referenced in IDS of 22 September 2023; Examiner has provided Espacenet Machine English-language translation), shows that instant formula 1 can be used in methods to treat the specific eye diseases of instant claim 22 (see page 8).
However, the broad and undefined scope of “eye diseases” of the independent claims 1, 3, and 11 cannot be prevented. Moreover, the eye diseases of claim 22 cannot be prevented. For example, the reference AMD (“7 Healthy Habits to Help Prevent Macular Degeneration.” University of Michigan Medicine. Published: 23 January 2019. Accessed 10 July 2026. Available from: < https://www.michiganmedicine.org/health-lab/7-healthy-habits-help-prevent-macular-degeneration / ), discloses that “doctors aren’t sure what causes age-related macular degeneration” (“AMD”) (page 1). Thus, if doctors do not know what causes it, they cannot prevent it. A patient can lower his chances of getting age-related macular degeneration (“AMD”) by not smoking, knowing family history, and eating well (see page 2). However, “lowering one’s chances” are not the same as “preventing”.
Similarly, the reference BEHCET (“Behcet’s Disease.” Cleveland Clinic. Accessed on 10 July 2026. Published: 2 June 2020. Available from: < https://my.clevelandclinic.org/health/diseases/12980-behcets-disease / >), discloses that scientists are not exactly sure what causes this disease (page 2). Thus, if doctors do not know what causes it, they cannot prevent it.
However, nothing in the prior art supports preventing the generic “eye diseases” of independent claims 1, 3, and/or 11 and nothing supports preventing the specific “eye diseases” of instant claim 22.
4. The Level of one of ordinary skill:
The level of one of ordinary skill includes the knowledge/skill to engage in a reasonable amount of experimentation to make and use the pharmaceutical compositions underlying the instant claims.
However, no one has skill to engage in the undue burdensome level of experimentation required to provide guidance/enablement for treating or preventing the unlimited/undefined scope of diseases/disorders of the instant method claims 1, 3, and 11 and preventing the specific eye diseases of instant claim 22.
5. The level of predictability in the art:
The art is predictable to make the instantly claimed pharmaceutical compositions. However, the art does not provide predictability as to which eye diseases and disorders can be treated or prevented beyond those reported, above, as known in the prior art. To generate this level of guidance, one has to engage in undue burdensome experimentation (since no predictability in the art) to test the pharmaceutical composition against every eye disease known to humanity to determine if the pharmaceutical composition can treat and/or prevent said disease(s). This level of experimentation would be required to match the scope of instant claims 1, 3, and 11 and many other claims.
6. The amount of direction provided by the inventor:
While the Specification provides enablement for treating CNV (one disease of instant claim 22) (see Test Example 2 pages 25-26 of Specification) with the instantly claimed pharmaceutical composition and shows that Applicants formulated said instantly claimed pharmaceutical formulation (see pages 19-26), the Specification does not provide direction for treating or preventing the undefined scope of eye diseases per the BRI of instant claims 1, 3, and/or 11 and the Specification does not provide enablement for treating or preventing the diseases of instant claim 22 (other than “treating” CNV [(see Test Example 2 pages 25-26 of Specification]).
7. The existence of working examples; and
While the Specification provides enablement for treating CNV (one disease of instant claim 22) (see Test Example 2 pages 25-26 of Specification) with the instantly claimed pharmaceutical composition and shows that Applicants formulated said instantly claimed pharmaceutical formulation (see pages 19-26), the Specification does not provide direction for treating or preventing the undefined scope of eye diseases per the BRI of instant claims 1, 3, and/or 11 and the Specification does not provide enablement for treating or preventing the diseases of instant claim 22 (other than CNV).
8. The quantity of experimentation needed to make or use the invention based on the content of the disclosure:
The undefined scope of eye diseases per the BRI of instant claims 1, 3, and 11 would require an undue amount of experimentation to use the invention as claimed to treat or prevent any eye disease with the instantly claimed pharmaceutical formulation.
Moreover, the amount of experimentation required to prevent any of the specific eye diseases of claim 22 would be undue as well, absent evidence in the Specification or prior art.
Therefore, claims 1-8, 11, and 14-22 are rejected under 35 USC 112(a) for lacking enablement for the scope of treating or preventing all eye diseases (per BRI of instant claims 1, 3, and 11) and for preventing the eye diseases of claim 22 with the instantly claimed pharmaceutical formulation.
To render moot this scope of enablement rejection: Applicants should delete “prevent” and/or “prevention”/”preventing” and synonyms thereof from all (emphasis) the claims and further define the scope of “eye diseases” that are treated (not “prevented”) within independent claims 1, 3, and 11.
Furthermore, Applicants should disclose the scope of diseases or disorders in claims 1, 3, and 11 for which Applicants believe their specification or the prior art provides guidance/enablement (perhaps by moving some of the species of diseases from claim 22 into independent claims 1, 3, and 11). Please point to specific Examples by example number and page number in Specification or specific prior art references and explain how those example(s)/reference(s) demonstrate the guidance/enablement needed that is currently missing.
Claim Rejections - 35 USC § 102
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.
Claims 1-2, 11, 14-15, 18, and 21-22 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by:
MOON (KR 101821593 B1, referenced in IDS of 22 September 2023; Examiner has provided Espacenet Machine English-language translation).
The prior art reference MOON teaches the compound 3-phenyl-4-propyl-1-(pyridin-2-yl)-1H-pyrazol-5-ol (otherwise known and referenced as “APX-115”):
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(see “Synthesis Example 1” on page 10 and “Synthesis Example 2” on page 11; see, also, pages 2 and 4-7). This is structurally identical to instant claims’ formula 1.
The prior art MOON reference also teaches a pharmaceutical composition comprising APX-115, or HCl “pharmaceutically acceptable salt thereof” as an active ingredient (see “Synthesis Example 1” on page 10 and “Synthesis Example 2” on page 11) being used in a method to treat eye disease (anticipates “for preventing or treating eye disease” of the instant claims) in a subject (animal model) in need thereof (Examples 4-8 on pages 13-15).
In fact, the Example 8 page 15 teaches a method for treating or preventing “choroidal neovascularization” (“CNV”) (Applicants’ elected “eye disease”) comprising administering APX-115 or its HCl pharmaceutically acceptable salt as an active ingredient to an animal model (“subject”) in need thereof. This teaches instant claims 21-22.
Since MOON is silent as to concentration of degradation product N-oxopyridine (instant Formula 2), the Office interprets this as “an amount less than about 3%” since no N-oxopyridine is “less than about 3%”. This anticipates instant claims 11 and 18.
Also, the Office interprets the limitation “for preventing or treating eye disease” as an intended use limitation. Nothing precludes the use as claimed.
MOON teaches that the pharmaceutical composition comprising APX-115 can be formulated into “eye drops” (see page 9).
MOON teaches “further comprising an antioxidant” as an additive (page 9).
Thus, the above anticipates instant claims 1-2 and 15.
MOON also teaches “solubilizing aids” of instant claim 14 (page 9).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-8, 11, and 14-22 are rejected under 35 U.S.C. 103 as being unpatentable over:
MOON (KR 101821593 B1, referenced in IDS of 22 September 2023; Examiner has provided Espacenet Machine English-language translation),
in view of:
THIOGLYCEROL (“Preservatives and Antioxidants Database.” Compounding Today. Accessed 9 July 2026. Published: 29 October 2005. Available from: < https://compoundingtoday.com/Preservative/ > ),
and in further view of:
ANSEL (Ansel, Howard C., et al. “Pharmaceutical Dosage Forms and Drug Delivery Systems.” (1999), 7th ed. Lippincott Williams & Wilkins, pp. 48-53).
The instant claims 3-8 and 16-22 are drawn to an eye drop for preventing or treating eye disease comprising instant formula I, or pharmaceutically acceptable salts thereof as an active ingredient; and at least one antioxidant. A concentration of “less than about 3%” of degradation product N-oxopyridine of instant formula 2 is also claimed. Various dependent claims also are drawn to concentrations of the above and shelf-life standards (“under a condition of about 25*C temperature and about 60% relative humidity”).
Determining the scope and contents of the prior art:
The prior art reference MOON teaches instant claims 1-2, 11, 14-15, 18, and 21-22, supra, and hence is incorporated by reference in its entirety.
MOON also further teaches addition of antioxidants as an adjuvant (page 9).
Since MOON is silent as to concentration of degradation product N-oxopyridine (instant Formula 2), the Office interprets this as “an amount less than about 3%” since no N-oxopyridine is “less than about 3%”. This teaches instant claim 7.
In fact, the MOON reference Example 8 page 15 teaches a method for treating or preventing “choroidal neovascularization” (Applicants’ elected “eye disease”) comprising administering APX-115 or its HCl pharmaceutically acceptable salt as an active ingredient to an animal model (“subject”) in need thereof. Further, because MOON teaches that the pharmaceutical composition comprising APX-115 can be formulated into “eye drops” (see page 9), it would be obvious to practice said method, above, with eye drops, thereby teaching the method of treating or preventing of instant claim 11. This also teaches instant claims 21-22.
The prior art reference THIOGLYCEROL teaches that monothioglycerol is an antioxidant (page 4 of 4). Furthermore, antioxidants such as monothioglycerol are added to pharmaceutical formulations to enhance physical and chemical stability of the pharmaceutical composition (pages 2-3 of 4).
The prior art reference ANSEL teaches that physicians routinely change (increase or decrease) the dosage to meet particular treatment requirements of their patients (see right column of page 48).
Ascertaining the differences between the prior art and the claims at issue:
While MOON teaches instant claims 1-2, 11, 14-15, 18, and 21-22, supra, and further teaches addition of antioxidants (see page 9), it does not teach compositions further comprising monothioglycerol.
While THIOGLYCEROL teaches that monothioglycerol is an antioxidant and that antioxidants are commonly used as adjuvants to enhance physical and chemical stability of the pharmaceutical composition (pages 2-3 of 4), the THIOGLYCEROL reference does not teach use of monothioglycerol in the formulations of the instant claims.
While ANSEL teaches that physicians routinely change (increase or decrease) the dosage to meet particular treatment requirements of their patients (see right column of page 48). However, ANSEL does not teach the specific weight percentages of claims 6 or 17.
Resolving the level of ordinary skill in the pertinent art:
The artisan is knowledgeable in formulating pharmaceutical compositions for treating or preventing eye diseases comprising 3-phenyl-4-propyl-1-(pyridin-2-yl)-1H-pyrazol-5-ol (“APX-115”), or pharmaceutically acceptable salts thereof, in eye drop form. The artisan is also knowledgeable in minimizing degradation products such as N-oxopyridine and so knows how to add antioxidant adjuvants such as monothioglycerol.
Considering objective evidence present in the application indicating obviousness or nonobviousness:
The instant claims are prima facie obvious in light of the combination of MOON in view of THIOGLYCEROL and in further view of ANSEL.
The addition of monothioglycerol antioxidant as an adjuvant to the pharmaceutical composition of MOON to increase its shelf-life is prima facie obvious.
The artisan would be expected to add monothioglycerol (Applicants’ elected species of “antioxidant”) as an antioxidant to the pharmaceutical formulation (as taught by MOON reference) comprising APX-115
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(see MOON “Synthesis Example 1” on page 10 and “Synthesis Example 2” on page 11; see, also, pages 2 and 4-7) since antioxidants are commonly added as adjuvants to pharmaceutical formulations (see THIOGLYCEROL (pages 2-4 of 4).
The artisan would be motivated to add monothioglycerol as an antioxidant to the APX-115 pharmaceutical formulation from MOON since monothioglycerol antioxidants are commonly used as adjuvants to enhance physical and chemical stability of the pharmaceutical composition (THIOGLYCEROL pages 2-3 of 4). Thus, the artisan would use monothioglycerol antioxidant as an adjuvant in the APX-115 pharmaceutical formulation (or HCl pharmaceutically acceptable salt thereof, taught by MOON, above) to enhance the physical and chemical stability/increase the shelf-life of the MOON APX-115 pharmaceutical composition. This teaches instant claims 3-5, 16, and 19-20.
Furthermore, the Examiner interprets the standard “under a condition of about 25*C temperature and about 60% relative humidity” as an industry standard for shelf-life/preservation. Thus, this along with the above also teaches instant claim 8.
Furthermore, the artisan, seeing the varying concentrations (weight percentages) of instant claims 6 and 17, would view as prima facie obvious the varying weight percentages (interpreted as concentrations) of monothioglycerol antioxidant. The artisan would view these varying percentage concentrations as variables that the artisan routinely optimizes to maximize the preservation of/shelf-life of the underlying APX-115 active pharmaceutical ingredient.
The artisan would be expected to vary the weight percentages of APX-115 in order to maximize shelf-life/preservation of APX-115. The artisan would be motivated to vary the concentration of monothioglycerol antioxidant (concentration/weight percentage is a variable that is routinely optimized in the pharmaceutical arts) according to instant claims 6 and 17 to optimize the shelf-life and preservation of APX-115. This is especially true since neither the claims nor the Specification indicate how the concentrations (weight percentages) within dependent (emphasis) claims 6 and 17 are critical. Moreover, the artisan would look to what is known in the pharmaceutical arts which shows that the medicinal artisan (for example, “physician” or “pharmacists”) routinely increases or decreases dosage (concentrations/weight percentages) to meet the particular requirements of the patient (see ANSEL, page 48).
Moreover, patent law views differences in concentration (herein, the varying ranges of weight percentages) as not supporting the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[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); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1848 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989)(Claimed ratios were obvious as being reached by routine procedures and producing predictable results); In re Kulling, 897 F.2d 1147, 1149, 14 USPQ2d 1056, 1058 (Fed. Cir. 1990)(Claimed amount of wash solution was found to be unpatentable as a matter of routine optimization in the pertinent art, further supported by the prior art disclosure of the need to avoid undue amounts of wash solution); and In re Geisler, 116 F.3d 1465, 1470, 43 USPQ2d 1362, 1366 (Fed. Cir. 1997)(Claims were unpatentable because appellants failed to submit evidence of criticality to demonstrate that that the wear resistance of the protective layer in the claimed thickness range of 50-100 Angstroms was "unexpectedly good"); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree "will not sustain a patent"); In re Williams, 36 F.2d 436, 438, 4 USPQ 237 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions."). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416, 82 USPQ2d 1385, 1395 (2007) (identifying "the need for caution in granting a patent based on the combination of elements found in the prior art."). See MPEP 2144.05(II)(A). This teaches instant claims 6 and 17.
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, 11, 14, 15, 18, and 21-22 are provisionally rejected on the ground of anticipatory nonstatutory double patenting as being unpatentable over claims 2-3, 5-6, and 17-18 of co-pending Application No. 17/756,266 (reference claims). The reference amended claims of 11 June 2026 and the instant amended claims of 16 April 2026 were used to write this rejection.
The method of reference claims 2-3, 5-6, and 17-18, which contain “an eye drop for preventing or treating eye diseases comprising: [instant] formula 1
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or HCl pharmaceutically acceptable salts thereof as active ingredient; and 0% of degradation product N-oxopyridine (0% is “less than about 3%”), further comprising a solubilizing agent, anticipates instant claims 1, 11, 14, 15, and 18, drawn to same. The reference claims are silent as to the concentration of degradation product N-oxopyridine of instant formula 2, so the Examiner is interpreting as “0%”. The reference claims 2-3 are also drawn to treating or preventing choroidal neovascularization (CNV) (Applicants’ elected “eye disease”) with said pharmaceutical formulation, thereby anticipating instant claims 21-22.
This is a provisional nonstatutory double patenting rejection as the reference claims have not yet been patented.
Filing a Terminal Disclaimer (TD) will render moot this rejection.
Claims 1-8, 11, and 14-22 are provisionally rejected on the ground of obviousness-type nonstatutory double patenting as being unpatentable over claims 2-3, 5-6, 8-9, and 17-22 of co-pending Application No. 17/756,266 (reference claims referenced as “‘266”),
in view of:
THIOGLYCEROL (“Preservatives and Antioxidants Database.” Compounding Today. Accessed 9 July 2026. Published: 29 October 2005. Available from: < https://compoundingtoday.com/Preservative/ > ),
and in further view of:
ANSEL (Ansel, Howard C., et al. “Pharmaceutical Dosage Forms and Drug Delivery Systems.” (1999), 7th ed. Lippincott Williams & Wilkins, pp. 48-53).
The reference amended claims of 11 June 2026 and the instant amended claims of 16 April 2026 were used to write this rejection.
Determining the scope and contents of the prior art:
The reference claims (of ‘266) 2-3, 5-6, and 17-18 teach the instant claims 1, 11, 14, 15, 18, and 21-22, drawn to same, per the above.
The prior art reference THIOGLYCEROL teaches that monothioglycerol is an antioxidant (page 4 of 4). Furthermore, antioxidants such as monothioglycerol are added to pharmaceutical formulations to enhance physical and chemical stability of the pharmaceutical composition (pages 2-3 of 4).
The prior art reference ANSEL teaches that physicians routinely change (increase or decrease) the dosage to meet particular treatment requirements of their patients (see right column of page 48).
Ascertaining the differences between the prior art and the claims at issue:
While THIOGLYCEROL teaches that monothioglycerol is an antioxidant and that antioxidants are commonly used as adjuvants to enhance physical and chemical stability of the pharmaceutical composition (pages 2-3 of 4), the THIOGLYCEROL reference does not teach use of monothioglycerol in the formulations of the instant claims.
While ANSEL teaches that physicians routinely change (increase or decrease) the dosage to meet particular treatment requirements of their patients (see right column of page 48). However, ANSEL does not teach the specific weight percentages of claims 6 or 17.
Resolving the level of ordinary skill in the pertinent art:
The artisan is knowledgeable in formulating pharmaceutical compositions for treating or preventing eye diseases comprising 3-phenyl-4-propyl-1-(pyridin-2-yl)-1H-pyrazol-5-ol (“APX-115”), or pharmaceutically acceptable salts thereof, in eye drop form. The artisan is also knowledgeable in minimizing degradation products such as N-oxopyridine and so knows how to add antioxidant adjuvants such as monothioglycerol.
Considering objective evidence present in the application indicating obviousness or nonobviousness:
The instant claims are prima facie obvious in light of the combination of ‘266 in view of THIOGLYCEROL and in further view of ANSEL.
The addition of monothioglycerol antioxidant as an adjuvant to the pharmaceutical composition of the reference claims to increase its shelf-life is prima facie obvious.
The artisan would be expected to add monothioglycerol (Applicants’ elected species of “antioxidant”) as an antioxidant to the pharmaceutical formulation (as taught by reference claims 2-3) comprising APX-115
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since antioxidants are commonly added as adjuvants to pharmaceutical formulations (see THIOGLYCEROL (pages 2-4 of 4).
The artisan would be motivated to add monothioglycerol as an antioxidant to the APX-115 pharmaceutical formulation from reference claims 2-3 since monothioglycerol antioxidants are commonly used as adjuvants to enhance physical and chemical stability of the pharmaceutical composition (THIOGLYCEROL pages 2-3 of 4). Thus, the artisan would use monothioglycerol antioxidant as an adjuvant in the APX-115 pharmaceutical formulation (or HCl pharmaceutically acceptable salt thereof, taught by reference claims 2-3, above) to enhance the physical and chemical stability/increase the shelf-life of the reference claims’ APX-115 pharmaceutical composition. This teaches instant claims 2-5, 7, 16-17, and 19-20.
Furthermore, the Examiner interprets the standard “under a condition of about 25*C temperature and about 60% relative humidity” as an industry standard for shelf-life/preservation. Thus, this along with the above also teaches instant claim 8.
Furthermore, the artisan, seeing the varying concentrations (weight percentages) of instant claims 6 and 17, would view as prima facie obvious the varying weight percentages (interpreted as concentrations) of monothioglycerol antioxidant. The artisan would view these varying percentage concentrations as variables that the artisan routinely optimizes to maximize the preservation of/shelf-life of the underlying APX-115 active pharmaceutical ingredient.
The artisan would be expected to vary the weight percentages of APX-115 in order to maximize shelf-life/preservation of APX-115. The artisan would be motivated to vary the concentration of monothioglycerol antioxidant (concentration/weight percentage is a variable that is routinely optimized in the pharmaceutical arts) according to instant claims 6 and 17 to optimize the shelf-life and preservation of APX-115. This is especially true since neither the claims nor the Specification indicate how the concentrations (weight percentages) within dependent (emphasis) claims 6 and 17 are critical. Moreover, the artisan would look to what is known in the pharmaceutical arts which shows that the medicinal artisan (for example, “physician” or “pharmacists”) routinely increases or decreases dosage (concentrations/weight percentages) to meet the particular requirements of the patient (see ANSEL, page 48).
Moreover, patent law views differences in concentration (herein, the varying ranges of weight percentages) as not supporting the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[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); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1848 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989)(Claimed ratios were obvious as being reached by routine procedures and producing predictable results); In re Kulling, 897 F.2d 1147, 1149, 14 USPQ2d 1056, 1058 (Fed. Cir. 1990)(Claimed amount of wash solution was found to be unpatentable as a matter of routine optimization in the pertinent art, further supported by the prior art disclosure of the need to avoid undue amounts of wash solution); and In re Geisler, 116 F.3d 1465, 1470, 43 USPQ2d 1362, 1366 (Fed. Cir. 1997)(Claims were unpatentable because appellants failed to submit evidence of criticality to demonstrate that that the wear resistance of the protective layer in the claimed thickness range of 50-100 Angstroms was "unexpectedly good"); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree "will not sustain a patent"); In re Williams, 36 F.2d 436, 438, 4 USPQ 237 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions."). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416, 82 USPQ2d 1385, 1395 (2007) (identifying "the need for caution in granting a patent based on the combination of elements found in the prior art."). See MPEP 2144.05(II)(A). This teaches instant claims 6 and 17.
This is a provisional nonstatutory double patenting rejection as the reference claims have not yet been patented.
Filing a Terminal Disclaimer (TD) will render moot this rejection.
Conclusion
No claims are presently allowable as written.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOHN S KENYON whose telephone number is (571)270-1567. The examiner can normally be reached Monday-Friday 10a-6p.
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/JOHN S KENYON/Primary Patent Examiner, Art Unit 1625
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