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 .
DETAILED ACTION
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 23 Jul 2026 has been entered.
Response to Amendment
Status of the Claims
Receipt of Applicant’s response, filed 23 Jul 2026 has been entered.
Claims 1, 3, 4, 6, 7, 9-15, 17, 18, and 20-22 remain pending in the application.
Claims 2, 5, 8, 16, and 19 are cancelled.
Claims 20-22 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
Claims 1, 3, 4, 6, 7, 9-15, 17 and 18 are under consideration to the extent of the elected species, i.e., that the preservative is benzalkonium chloride, the chelating agent is EDTA, the anti-oxidant is sodium metabisulfite, the polymer is hydropropylmethylcellulose, the buffering agent is phosphate buffers, the tonicity agent is sodium chloride and the pH adjusting agent is sodium hydroxide.
Rejections Maintained
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, 3, 4, 6, 7, 9, 10, 12-15, 17 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Buono (US 2004/0013729, published 22 Jan 2004, listed in IDS filed 29 June 2023) in view of Matsumura (US 20180161438, published 14 Jun 2018).
Buono teaches single drop multiple agent compositions for topical delivery to the eye (title). Buono teaches that the compositions include mydriatic agents such as phenylephrine ([0014]) and cycloplegic agents such as atropine ([0015]). Buono teaches that the phenylephrine may be at 2.5% ([0042]), rendering obvious the amount of phenylephrine in claims 3 and 4. Buono teaches example compositions such as composition B which include cyclopentolate at 0.1%. Cyclopentolate is an alternative cycloplegic agent to atropine ([0015]). Buono teaches that the components come in solution form and can be combined together ([0042]), rendering obvious that the composition is in the form of a solution, as in instant claim 17. Buono teaches that the compositions are at physiologically acceptable pH ([0042]). Buono teaches the inclusion of a viscoelastic polymer such as hydroxypropylmethylcellulose (HPMC) ([0017]), rendering obvious claim 12.
Buono does not teach that the pH of the solutions is between 3.5 to 8.5 or that the atropine is at 0.01 as in claim 7 or the inclusion of excipients such as benzalkonium chloride, EDTA, phosphate buffers, sodium chloride and sodium hydroxide. These deficiencies are made up for in the teachings of Matsumura.
Matsumura teaches aqueous ophthalmic compositions (title). Matsumura teaches the compositions may have phenylephrine ([0126]). Matsumura teaches that the ophthalmic compositions have a pH within a medically pharmacologically acceptable range such as 4.0 to 9.5 ([0170]), rendering obvious the pH range of claim 1. Matsumura teaches that atropine sulfate may be in the composition from 0.0001 to 0.01 w/v% ([0122]-[0125]). Matsumura teaches the inclusion of components including preservatives such as benzalkonium chloride ([0030]) and chelating drugs such as EDTA ([0182]), rendering obvious claims 9 and 10. Matsumura teaches the inclusion of a buffer such as a phosphoric acid buffer such as dipotassium phosphate ([0160]-]0162]), rendering obvious claim 13. Matsumura teaches the inclusion of inorganic salts such as sodium chloride ([0010], [0024]), rendering obvious claim 14. Matsumura further teaches the inclusion of sodium hydroxide in appropriate amounts ([0209] Table 3), rendering obvious claim 15.
Therefore, it would have been prima facie obvious to one of ordinary skill in the
art, before the effective filing date of the claimed invention to have formed the composition of Buono with phenylephrine at 2.5%, atropine from 0.001 to 0.01%, the pH from 4.0 to 9.5 and to have included HPMC, benzalkonium chloride, EDTA, phosphoric acid buffers such as dipotassium phosphate, sodium chloride and sodium hydroxide. Compositions for the eye with multiple agents such as 2.5% phenylephrine and atropine and also HPMC are known from Buono. Including atropine in low amounts such as 0.1% is obvious as Buono indicates other cycloplegic agents such as cyclopentolate are at 0.1%. It is further known that atropine sulfate may be included in opthlamic compositions ranging from 0.0001 to 0.01 w/v% by Matsumura. Thus, one would have a reasonable expectation of success in including the atropine from 0.0001 to 0.01 w/v% as Buono indicates low percentages of cycloplegic agents and the specific range of 0.0001 to 0.01% is known as suitable for ophthalmic compositions. Having the compositions at physiological pH is indicated by Buono and physiological pH includes pH levels from 4.0 to 9.5, as taught by Matsumura. Thus, it would have been obvious to have the compositions from pH 4.0 to 9.5 as this is a known physiological pH range indicating that it would be compatible for a patient. The inclusion of HPMC in the compositions is known from Buono and benzalkonium chloride, EDTA, phosphoric acid buffers such as dipotassium phosphate, sodium chloride and sodium hydroxide are likewise known as suitable components for ophthalmic compositions rendering it obvious to one of ordinary skill to include them as they are known to be suitable for ophthalmic compositions and their inclusion thus merely represents the use of known prior art elements for their intended purpose in a similar composition.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references.
Response to Arguments
Applicant's arguments filed 23 Jul 2026 have been fully considered but they are not persuasive. Applicant argues that Buono mandates a viscoelastic polymer where the present claims do not (page 8 of remarks). The examiner is not persuaded by this as the claims are open to the inclusion of a polymer through the use of “comprising” language and is an optional ingredient of claim 1and a polymer such as hydroxypropyl methylcellulose (i.e. a viscoelastic polymer of Buono) is even required in claim 12. Reciting the polymer in claim 1 as an optional ingredient does not distinguish the invention from the prior art, even if the art has the polymer as a required component and not an optional component.
Applicant argues that Buono does not disclose the use of atropine at ultra-low concentrations such as 0.01% (page 8 of remarks). Applicant argues that Buono does not disclose a pH range for its compositions while the present invention requires a pH range from about 3.5-8.5 (page 8 of remarks). The examiner is not persuaded by this as these deficiencies are made up for in the teachings of Matsumura. The examiner notes that one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). As noted in the rejection above, it is obvious from Matsumura for ophthalmic compositions to include atropine sulphate in a concentration of from 0.0001 to 0.01 w/v% and to have the pH within a medically pharmacologically acceptable range such as 4.0 to 9.5. Buono indicates low percentages of cycloplegic agents and having compositions at physiological pH, rendering it obvious to have the atropine and pH in the composition of Buono at these ranges as they are known as suitable for ophthalmic compositions.
Applicant argues that there is a synergistic effect between a mydriatic agent and an ultra-low concentration of anti-muscarinic agent that prohibits paralysis of ciliary muscles due to low concentration of atropine where the prior art teaches an amount sufficient to cause cycloplegia (page 8 of remarks). Applicant argues that they have shown stability for 2.5% phenylephrine and 0.01% atropine and the prior art does not discuss this stability (page 9 of remarks). The examiner is not persuaded by this as the synergistic effect and stability noted by the applicant would be a necessary consequence or property from the combination of the atropine and phenylephrine and "The fact that appellant 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." Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985). As described above, the combination of the components in the claimed amounts is obvious from the prior art and the applicant has not pointed to any data that would support a conclusion that the synergistic effect or the claimed stability noted by the applicant should be understood as an unexpected result.
Applicant argues that Matsumura requires Vaseline where the present invention does not require Vaseline (page 16 of remarks). Applicant argues that Matsurmura does not disclose phenylephrine and atropine as the mydriatic/anti-muscarinic active pair (page 16 of remarks). Applicant argues that Matsumura does not give a concentration range specific to atropine or phenylephrine as a mydriatic pair (page 16 of remarks). These arguments are not persuasive as they do not address or undermine the basis or rationale on which the rejection relies. This is because "[T]he test for obviousness is what the combined teachings of the references would have suggested to [a PHOSITA]." In re Mouttet, 686 F.3d 1322, 1333, 103 USPQ2d 1219, 1226 (Fed. Cir. 2012). Matsumura is used for the teachings regarding the obviousness of the range of atropine concentrations and pH in ophthalmic compositions and including specific excipients. It is not necessary to include Vaseline from the combination as made, but even still, the composition is open to alternative components such as Vaseline. Further, it is not necessary for Matsumura to teach a specific embodiment with atropine and phenylephrine in combination in the claimed amounts as the combination of components is obvious over the combined teachings of Buono in view of Matsumura for the reasons provided above.
Thus, the examiner maintains that the claims are obvious for the reasons provided above.
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Buono (US 2004/0013729, published 22 Jan 2004, listed in IDS filed 29 June 2023) in view of Matsumura (US 20180161438, published 14 Jun 2018) as applied to Claims 1, 3, 4, 6, 7, 9, 10, 12-15, 17 and 18 above and further in view of Ostrow et al. (US 2015/0366854, published 24 Dec 2015)
The teachings of Buono and Matsumura are described supra. Buono and Matsumura do not teach the inclusion of sodium metabisulfite. This deficiency is made up for in the teachings of Ostrow.
Ostrow teaches ophthalmic compositions (title). Ostrow teaches the inclusion of components such as atropine and atropine sulfate ([0003]) from 0.001 to about 0.02 wt% ([0010]) further supporting the obviousness of the concentration of atropine described in the rejection above. Ostrow teaches the inclusion of ophthalmically acceptable antioxidants, such as sodium metabisulfite, to enhance chemical stability ([0139]).
Therefore, it would have been prima facie obvious to one of ordinary skill in the
art, before the effective filing date of the claimed invention to have included sodium metabisulfite into the composition obvious over Buono and Matsumura. Similar compositions as Buono and Matsumura for ophthalmic use and comprising atropine are taught by Ostrow. Sodium metabisulfite is a known antioxidant suitable for such compositions and offers benefits such as enhancing chemical stability. Thus, it would have been obvious to include sodium metabisulfite in the compositions for its use as an antioxidant and ability to enhance chemical stability.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references.
Response to Arguments
Applicant's arguments filed 23 Jul 2026 have been fully considered but they are not persuasive. Applicant argues that Ostrow requires the muscarinic antagonist to be formulated with deuterated water where the present invention is formulated with conventional water (page 13 of remarks). Applicant argues that Ostrow is directed to arresting or preventing myopia where the present invention is directed to inducing pupil dilation (page 13 of remarks). Applicant argues that Ostrow does not optimize a specific fixed dose therapeutic ratio where the claimed invention is targeted to 2.5% phenylephrine hydrochloride and 0.01% atropine sulphate and that Ostrow does not actively eliminate the mechanism of cycloplegia (page 14 of remarks). These arguments are not persuasive as they do not address or undermine the basis or rationale on which the rejection relies. This is because "[T]he test for obviousness is what the combined teachings of the references would have suggested to [a PHOSITA]." In re Mouttet, 686 F.3d 1322, 1333, 103 USPQ2d 1219, 1226 (Fed. Cir. 2012). Additionally, the examiner notes that one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Ostrow is used merely to indicate the obviousness of including an antioxidant such as metabisulfite in ophthalmic solutions. It is not necessary to include deuterated water based on the applied combination, although nothing in the claim would prevent using deuterated water. Noting that Ostrow teaches an embodiment preventing myopia whereas the instant invention is directed to pupil dilation does not overcome the obviousness of including an antioxidant in ophthalmic compositions, which is what Ostrow is relied upon for. Further, it is not necessary for Ostrow to optimize a specific fixed dose of phenylephrine and atropine as Ostrow is not relied upon for the concentration of the atropine and phenylephrine components as this is obvious from the combination of Buono and Matsumura.
New Grounds of Rejection
Claim Objections
Claim 18 is objected to because of the following informalities: Claim 18 is missing a period. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 9, 10, 12, and 13 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 12 recites “hyaluronic acid (sodium hyaluronate).” Sodium hyaluronate is a specific salt form of hyaluronic acid and it is not clear if the claim is intended to require sodium hyaluronate or if this is merely exemplary of hyaluronic acid.
Claim 9 recites the limitation "the preservative". There is insufficient antecedent basis for this limitation in the claim. Base claim 1 recites “one or more preservative”, which encompasses multiple preservatives, and it is unclear whether “the preservative” includes just one or more than one preservative. Amending claim 9 to recite “one or more preservative” would overcome this rejection.
Claim 10 recites the limitation "the chelating agent". There is insufficient antecedent basis for this limitation in the claim. Base claim 1 recites “one or more chelating agent”, which encompasses multiple chelating agent, and it is unclear whether “the chelating agent” includes just one or more than one preservative. Amending claim 9 to recite “one or more chelating agent” would overcome this rejection.
Claim 13 recites the limitation "the buffering agent". There is insufficient antecedent basis for this limitation in the claim. Base claim 1 recites “one or more buffering agent”, which encompasses multiple buffering agent, and it is unclear whether “the buffering agent” includes just one or more than one preservative. Amending claim 9 to recite “one or more buffering agent” would overcome this rejection.
Conclusion
No claim is allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to EDWIN C MITCHELL whose telephone number is (571)272-7007. The examiner can normally be reached Mon-Fri 8:00-5:00.
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/EDWIN COLEMAN MITCHELL/Examiner, Art Unit 1619
