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
2. This Office Action is responsive to Applicant’s Amendment and Remarks, filed February 6, 2026. The amendment, filed February 6, 2026, is entered, wherein claims 57 and 68 are amended, claims 1 – 56, 58, 62 – 63, 69, 71, 73, 77 – 78, 82, and 84 are canceled, and claims 64 and 79 are withdrawn.
Claims 57, 59 – 61, 64 – 68, 70, 72, 74 – 76, 79 – 81, and 83 are pending in this application and claims 57, 59 – 61, 65 – 68, 70, 72, 74 – 76, 80 – 81, and 83 are currently examined.
Priority
This application is a national stage application of PCT/AU2019/050986, filed September 13, 2019, which claim benefit of foreign priority document AU201803445, filed September 13, 2018.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/02/2025 was filed after the mailing date of the previous Office Action on June 2, 2025. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Withdrawn Rejections
5. The rejection of claims 57 and 65 – 66 in the previous Office Action, mailed June 2, 2025, under 35 U.S.C. 103 as being unpatentable over Carr et al. with evidence provided by Ellis in view of Virno et al. has been considered and is withdrawn in view of the amended claim 57.
The rejection of claims 59 – 61 and 67 in the previous Office Action, mailed June 2, 2025, under 35 U.S.C. 103 as being unpatentable over Carr et al. with evidence provided by Ellis and Virno et al. as applied to claims 57 – 58 and 65 – 66 above, and further in view of Pramar with evidence provided by Agarwal has been considered and is withdrawn in view of the amended claim 57.
The rejection of claims 68 and 80 – 81 in the previous Office Action, mailed June 2, 2025, under 35 U.S.C. 103 as being unpatentable over Carr et al. with evidence provided by Ellis and Virno et al. as applied to claims 57 – 58 and 65 – 66 above, and further in view of Timmins has been considered and is withdrawn in view of the amended claim 68.
The rejection of claims 70, 72, 74 – 76, and 83 in the previous Office Action, mailed June 2, 2025, under 35 U.S.C. 103 as being unpatentable over Carr et al. with evidence provided by Ellis in view of Virno et al. and Timmins as applied to claims 57 – 58, 65 – 66, 68, and 80 – 81 above, and further in view of Masters et al. has been considered and is withdrawn in view of the amended claims 57 and 68.
The rejection of claims 68, 80 – 81, and 83 in the previous Office Action, mailed June 2, 2025, on the ground of nonstatutory double patenting as being unpatentable over claims 1 - 20 of U.S. Patent No. 10874629B2 and Carr et al., as applied to claims 57 – 61 and 65 – 67 above, and further in view of Timmins has been considered and is withdrawn in view of the amended claim 68.
The rejection of claims 70 and 72 – 76 in the previous Office Action, mailed June 2, 2025, on the ground of nonstatutory double patenting as being unpatentable over claims 1 - 20 of U.S. Patent No. 10874629B2 and Carr et al., and Timmins, as applied to claims 57 – 61, 65 – 68, 80 – 81, and 83 above, and further in view of Masters et al. has been considered and is withdrawn in view of the amended claim 68.
The rejection of claims 57 – 61 and 65 – 66 in the previous Office Action, mailed June 2, 2025, on the ground of nonstatutory double patenting as being unpatentable over claims 1 - 21 of U.S. Patent No. 11890266B2 in view of Carr et al. has been considered and is withdrawn in view of the amended claim 57.
The rejection of claim 67 in the previous Office Action, mailed June 2, 2025, on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 21 of U.S. Patent No. 11890266B2 and Carr et al., as applied to claims 57 – 61 and 65 – 66 above, and further in view of Pramar with evidence provided by Agarwal has been considered and is withdrawn in view of the amended claim 57.
The rejection of claims 68 and 73 – 76, 80 – 81, and 83 in the previous Office Action, mailed June 2, 2025, on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 21 of U.S. Patent No. 11890266B2, Carr et al., and Pramar with evidence provided by Agarwal, as applied to claims 57 – 61 and 65 – 67 above, and further in view of Timmins has been considered and is withdrawn in view of the amended claim 68.
The rejection of claims 70 and 72 in the previous Office Action, mailed June 2, 2025,on the ground of nonstatutory double patenting as being unpatentable over claims 1 - 21 of U.S. Patent No. 11890266B2, Carr et al., Pramar with evidence provided by Agarwal, and Timmins, as applied to claims 57 – 61, 65 – 68, 73 – 76, 80 – 81, and 83 above, and further in view of Masters et al. has been considered and is withdrawn in view of the amended claims 57 and 68.
The following are modified / new grounds of rejection necessitated by Applicant’s Amendment and Remarks, filed February 6, 2026, wherein claims 57 and 68 are amended, claims 1 – 56, 58, 62 – 63, 69, 71, 73, 77 – 78, 82, and 84 are canceled, and claims 64 and 79 are withdrawn. Previously and newly cited references have been used to establish the modified / new grounds of rejection.
Modified / New 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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
i. Determining the scope and contents of the prior art.
ii. Ascertaining the differences between the prior art and the claims at issue.
iii. Resolving the level of ordinary skill in the pertinent art.
iv. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 57, 59 – 61, and 65 – 67 are rejected under 35 U.S.C. 103 as being unpatentable over Carr et al. (University of Utah Health Sciences Center, 2017, cited in the previous Office Action) in view of Spiers (British Medical Journal, 1969, Vol. 4, page 333 – 335, Reference included with PTO-892), Zhou et al. (Progress in Retinal and Eye Research, 2017, Vol. 61, page 60 – 71, Reference included with PTO-892), and Lee et al. (EP0834308A1).
a. Regarding claims 57, 59 – 61, and 65 – 67, Carr et al. teach that myopia is the most common refractive vision disorder in children, and the underlying biological cause of myopia is still unknown (Abstract, para. 1 – 2). There are substantial link to the up-regulation of neuromodulators, such as dopamine and nitric oxide. These neurotransmitters are strongly correlated with myopia-inhibition on their own and they may work together in the same myopia-inhibiting pathway (page 8, para. 1). Many studies have shown that various signaling molecules found in amacrine cells can affect myopia onset and inhibition, such as dopamine (page 14, para. 4). Carr et al. state that there is strong evidence that dopamine is a very important molecule in myopia-inhibition and regulation of eye growth based on the studies conducted (page 18, para. 3). Carr et al. also disclose a two-year, comprehensive, randomized, placebo-controlled, double-blind trial of 346 Asian children for determining effectiveness and safety of daily 1% atropine eye drops for the prevention of myopia progression; 84% of placebo-treated experienced myopic progression; while only 34% of atropine-treated experienced the same (page 27, para. 1). Moreover, Carr et al. teach that one of the most effective anti-myopia GABAergic drugs is the GABAaOr/C antagonist (1,2,5,6-Tetrahydropyridin-4-yl)methylphosphinic acid (TPMPA), which has been shown to significantly inhibit goggle-induced myopic retractive error, vitreal chamber depth, and equatorial diameter in the chick and guinea pig (page 24, para. 1).
However, Carr et al. do not teach a method comprising topically administer one or more eye drops to an eye of the subject, wherein the eyedrops comprises dopamine and an aqueous carrier, wherein the aqueous carrier is an aqueous buffer. Carr et al. do not teach that the composition further comprises an antioxidant, wherein the antioxidant is sodium bisulfite. Carr et al. also do not teach the composition is formulated for penetration of dopamine through the corneal epithelium.
Spiers teaches dopamine eye drops, wherein the eye drops of dopamine are made up in 10% solution buffered with sodium bicarbonate and sodium sulphite. The drops are instilled into one eye during each study (page 333, Right Col., para. 3).
Zhou et al. teach that local administration of APO and dopamine by eye drops may achieve therapeutic effects on myopia with reduced systemic side effects (page 67, Left Col., para. 1).
Lee et al. teach an ophthalmic formulation for treating myopia, which comprises a dopamine agonist and cyclodextrin or its derivative in combination with a pharmaceutically acceptable carrier (Abstract). Lee et al. disclose that sodium bisulfate has been used as an antioxidant for dopamine agonist.
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date to modify the formulation of dopamine for the treatment of myopia as taught by Carr et al. into a topical formulation, such as eye drop, in view of Spiers and Zhou et al. because Carr et al. teach that dopamine may inhibit myopia and regulate eye growth, Spiers teaches that dopamine may be formulated as eye drops, and Zhou et al. teach that local administration of dopamine by eye drops may achieve therapeutic effects of myopia with reduced systemic side effects. One would have been motivated to modify the formulation of dopamine for the treatment of myopia as taught by Carr et al. into a topical formulation, such as eye drop, in view of Spiers and Zhou et al. because topical administration of dopamine by eye drop is known in the art and Zhou et al. teach that eye drop of dopamine may achieve therapeutic effects on myopia with reduced systemic side effects. It would have been obvious to formulate eye drop of dopamine as taught by Carr et al., Spiers, and Zhou et al. with an antioxidant, such as sodium bisulfate, in view of Lee et al. because Lee et al. teach that sodium bisulfate is known in the art for the oxidative effect toward dopamine agonist. One of ordinary skill in the art would have expected that incorporating an antioxidant, such as sodium bisulfate, into the dopamine formulation would prevent oxidation of dopamine, thereby improving stability. It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to combine dopamine with TPMPA and atropine as taught by Carr et al. for treating myopia because Carr et al. disclose that dopamine, TPMPA, and atropine are effective against myopia progression. It would have been obvious for one of ordinary skill in the art to combine dopamine with TPMPA and atropine as taught by Carr et al. for treating myopia because these drugs are known in the prior art for the purpose of treating myopia, and it would have been obvious to combine them to treat the same disease. As Spiers and Zhou et al. teach that dopamine may be formulated as eye drops and will achieve therapeutic effects on myopia, one of ordinary skill in the art would have expected that the dopamine in eye drop formulation would penetrate the corneal epithelium upon topical administration as such penetration is necessary for dopamine to reach ocular tissue and produce the therapeutic effect on myopia. One of the ordinary skill in the art would have had a reasonable expectation of success to modify the formulation of dopamine for the treatment of myopia as taught by Carr et al. into a topical formulation, such as eye drop, in view of Spiers and Zhou et al. because Carr et al. teach that dopamine is effective in inhibiting myopia, Spiers teaches that dopamine eye drop is known in the art, and Zhou et al. teach the benefit of formulating dopamine as eye drop. One of ordinary skill in the art would have had a reasonable expectation of success to combine dopamine with TPMPA and atropine as taught by Carr et al. for treating myopia because it is well known to combine drugs to treat the same disease.
Claims 68, 70, 72, 74 – 76, 80 – 81, and 83 are rejected under 35 U.S.C. 103 as being unpatentable over Carr et al. (University of Utah Health Sciences Center, 2017, cited in the previous Office Action) in view of Spiers (British Medical Journal, 1969, Vol. 4, page 333 – 335, Reference included with PTO-892), Zhou et al. (Progress in Retinal and Eye Research, 2017, Vol. 61, page 60 – 71, Reference included with PTO-892), and Lee et al. (EP0834308A1), as applied to claims 57, 59 – 61, and 65 – 67 above, and further in view of Schneider et al. (British Journal of Clinical Pharmacology, August 2018, Vol. 84, Issue 10, page 2422 – 2432, Reference included with PTO-892).
b. Regarding claims 68, 70, 72, 74 – 76, 80 – 81, and 83, the references teach the limitations discussed above.
However, these references do not teach that the composition comprises deuterated dopamine as well as the structure and name of the deuterated dopamine.
Schneider et al. teach the structure of dopamine:
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,
wherein the * represents deuterated positions (page 2424, Figure 1). Animal studies show that deuteration at α- and β-carbon slows down the breakdown of deuterated dopamine by monoamine oxidase and dopamine β-hydroxylase (page 2423, para. 3).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to substitute dopamine as taught by Carr et al. with deuterated dopamine in view of Schneider et al. because Schneider et al. teach that deuteration of dopamine at α- and β-carbon is known to slow metabolism or breakdown. One would have been motivated to substitute dopamine as taught by Carr et al. with deuterated dopamine in view of Schneider et al. because Schneider et al. teach that such deuteration slows metabolic breakdown of dopamine, thereby improving metabolic stability of dopamine. One would have performed routine experimentation to discover the number of deuteration on α- and β-carbon for the optimal metabolic stability. For claim 70, Schneider et al. teach that * represents deuterated positions in dopamine and further teach that deuteration at α- and β-carbon slows metabolic breakdown of dopamine. It would have been obvious for one of ordinary skill in the art to select dopamine deuterated at the α- and β-carbon, including dopamine-1,1,2,2-d4, because this species corresponds to deuteration at the α- and β-carbon as taught by Schneider et al. for improving metabolic stability of dopamine. One of ordinary skill in the art would have had a reasonable expectation of success to substitute dopamine as taught by Carr et al. with deuterated dopamine in view of Schneider et al. because it is known in the art that deuterated dopamine at the α- and β-carbon will improve the metabolic stability of dopamine.
Responses to Applicant’s Remarks:
Applicant’s Remarks, filed February 6, 2026, have been fully considered and are found to be not persuasive.
For the Declaration that was referenced in the response filed April 8, 2025, Applicant confirms that the Declaration was not uploaded. The Declaration is now filed along with the current Applicant’s Remarks. Regarding the Declaration, Professor Morgan notes that the instant application directly addresses the issue of topical ocular administration with the aim of applying the composition to the sites of action within the eye that are relevant for the control of myopia whilst minimizing extra-ocular actions and the present invention overcomes the problems with topical administration and is found to be capable of penetrating the corneal epithelium to the posterior segment of the eye. Therefore, Applicant argues that the combination of Carr et al., Ellis, and Virno et al. does not suggest treatment of myopia via topical administration of eye drops comprising dopamine as required by the presently amended claims.
Regarding Carr et al., Applicant argues that Carr et al. do not discuss or propose clinical application for dopamine. Applicant argues that Carr et al. do not tach or suggest topical administration of dopamine.
Regarding Ellis and Virno et al., Applicant argues that these references fail to address the deficiencies of Carr et al. because Virno et al. teach that eye drops containing dopamine have no effect on interocular pressure. The skilled artisan would understand that dopamine administered via eye drops will not reach the anterior segment of the eye. For Ellis, Applicant argues that eye drop treatment is a very poor way to drive drug to posterior tissues because Ellis teach that only a small amount of drug is present on the eye for a very short time. A person having ordinary skill in the art would not be motivated to substitute the generic route of administering dopamine as taught by Carr et al. with topical administration of dopamine in view of Virno et al. and Ellis and the skilled person would not have had a reasonable expectation of success at arriving at the claimed invention based on the cited references because of the above arguments.
Regarding Agarwal, Applicant argues that nothing in Agarwal suggests to formulate a drug as eye drops for increasing penetration and that Agarwal teaches away from aqueous formulation because of the potential toxicity. The skilled artisan would be motivated not to include BAK to minimize the toxicity of the formulation.
Regarding Pramar, Applicant argues that Pramar does not describe any use of dopamine or deuterated dopamine, but merely describes ophthalmic solutions generally. The skilled artisan would not be motivated to combine either Pramar or Agarwal with Carr et al., Ellis, and Virno et al. because neither Pramar nor Agarwal rectify the deficiency.
Regarding Timmins, Applicant argues that Timmins makes no reference to dopamine or deuterated dopamine and that there is no teaching or suggestion that deuteration of all compounds will be beneficial. Applicant argues that Timmins does not teach or suggest the penetration of dopamine to the posterior segment of the eye via eye drops.
Regarding Masters et al., Applicant argues that Masters et al. only concerns deuterated dopamine generally, but provide no teaching or suggestion using deuterated dopamine to treat any diseases. There is no teaching in Masters et al. that teach or suggests the penetration of dopamine to the posterior segment of the eye and the therapeutic effect of dopamine on myopia. Applicant argues that it is only in hindsight that the ordinary skilled artisan would have been motivated to combine Masters et al. with Carr et al., Ellis, Virno et al., and Timmins.
However, these arguments are moot because the previous rejections over Carr et al. in view of Virno et al. have been withdrawn. The new rejection is relied upon the combination of Carr et al., Spiers, Zhou et al., and Lee et al., and further in view of Schneider et al. Carr et al. teach that dopamine is capable of inhibiting myopia. Spiers teaches that dopamine eye drop is known in the art. Zhou et al. teach that local administration of dopamine by eye drop may achieve therapeutic effect on myopia with reduced systemic side effects. Lee et al. teach commonly used antioxidant for dopamine agonist. Schneider et al. teach that deuterated dopamine at the α- and β-carbon improve metabolic stability. The combination of these references teach the limitations of the claimed method, and therefore, render the claims obvious. Moreover, Zhou et al. explicitly teaches that local administration of dopamine eye drop may achieve therapeutic effect on myopia, thereby suggesting that topically administered dopamine is capable of reaching relevant ocular tissues. Accordingly, The Declaration is not sufficient to establish that penetration of dopamine to posterior segment would have been unexpected, or that such penetration is contrary to the teachings of Zhou et al.
Modified / New 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 57, 59 – 61 and 65 – 67, are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 - 20 of U.S. Patent No. 10874629B2 in view of Carr et al. (University of Utah Health Sciences Center, 2017, cited in the previous Office Action).
a. Regarding claims 57, 59 – 61 and 65 – 67, ‘629B2 teaches a method of inhibiting the progression or development of a visual disorder not associated with Parkinson’s disease in a subject in need, comprising topically administering to an eye of the subject a composition comprising levodopa, an antioxidant, and an aqueous carrier, wherein the visual disorder is myopia (claims 1 – 3). The aqueous carrier is selected from the group consisting of saline, water, aqueous buffer, and aqueous solution comprising water and a miscible solvent, and combinations thereof (claim 16). The antioxidant is selected from the group consisting of ascorbic acid, phenolic acids, sorbic acid, sodium bisulfite, sodium metabisulfite, acetyl cysteine, sodium thiosulfate, ethylene diamine tetraacetic acid, sodium nitrite, ascorbyl stearate, ascorbyl palmitate, alpha-thioglycerol, erythorbic acid, cysteine hydrochloride, citric acid, tocopherol or vitamin E, tocopherol acetate, dibutylhydroxytoluene, soybean lecithin, sodium thioglycolate, butylhydroxyanisole, propyl gallate, uric acid, melatonin, thiourea, and salts and combinations thereof (claim 4). ‘629B2 also teaches that the composition used in the method further comprises a muscarinic acetylcholine receptor antagonist, wherein the muscarinic acetylcholine receptor antagonist is atropine (claims 14 – 15). The composition may further comprises GABA receptor antagonist, wherein the GABA receptor antagonist is selected from bicuculline, flumazenil, gabazine, phenylenetetrazol, (1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid, (3-aminopropyl)(cyclohexylmethyl)phosphinic acid, and salts and combinations thereof (claims 12 – 13). The composition is formulated in the form of eye drop for levodopa to penetrate through the corneal epithelium (claims 19 – 20).
However, ‘629B2 does not explicitly teach administering dopamine to an eye of a subject.
Carr et al. teaches that myopia is the most common refractive vision disorder in children, and the underlying biological cause of myopia is still unknown (Abstract, para. 1 – 2). However, Carr et al. states that there is strong evidence that dopamine is a very important molecule in myopia-inhibition and regulation of eye growth based on the studies conducted (page 18, para. 3).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to substitute levodopa as taught by ‘629B2 with dopamine taught by Carr et al., as described above, because it is obvious to substitute the composition for the same purpose to achieve predictable results. One would have been motivated to simply use dopamine with the eye drop formulation that has an enhanced penetration, instead of the precursor, in the treatment of myopia. ‘629B2 also does not explicitly disclose the order of administering dopamine and atropine. However, ‘629B2 discloses that the composition is administered in the form of an eye drop and this implies that the two active ingredients will be administered together in the form of an eye drop. Therefore, one of skill in the art would have a reasonable expectation of success to substitute levodopa as taught by ‘629B2 with dopamine taught by Carr et al. to treat myopia as ‘629B2 teaches all the limitations and Carr et al. teaches that dopamine is important for myopia-inhibition.
Claims 68, 70, 72, 74 – 76, 80 – 81, and 83 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 - 20 of U.S. Patent No. 10874629B2 and Carr et al. (University of Utah Health Sciences Center, 2017, cited in the previous Office Action), as applied to claims 57, 59 – 61 and 65 – 67 above, and further in view of Schneider et al. (British Journal of Clinical Pharmacology, August 2018, Vol. 84, Issue 10, page 2422 – 2432, Reference included with PTO-892).
b. Regarding claims 68, 70, 72, 74 – 76, 80 – 81, and 83, the references teach the limitation as discussed above.
However, these references do not teach the method of inhibiting the development or progression of visual disorder, such as myopia, using a composition comprising deuterated dopamine.
Schneider et al. teach the structure of dopamine:
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,
wherein the * represents deuterated positions (page 2424, Figure 1). Animal studies show that deuteration at α- and β-carbon slows down the breakdown of deuterated dopamine by monoamine oxidase and dopamine β-hydroxylase (page 2423, para. 3).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to substitute dopamine as taught by ‘629B2 and Carr et al. with deuterated dopamine in view of Schneider et al. because Schneider et al. teach that deuteration of dopamine at α- and β-carbon is known to slow metabolism or breakdown. One would have been motivated to substitute dopamine as taught by ‘629B2 and Carr et al. with deuterated dopamine in view of Schneider et al. because Schneider et al. teach that such deuteration slows metabolic breakdown of dopamine, thereby improving metabolic stability of dopamine. One would have performed routine experimentation to discover the number of deuteration on α- and β-carbon for the optimal metabolic stability. For claim 70, Schneider et al. teach that * represents deuterated positions in dopamine and further teach that deuteration at α- and β-carbon slows metabolic breakdown of dopamine. It would have been obvious for one of ordinary skill in the art to select dopamine deuterated at the α- and β-carbon, including dopamine-1,1,2,2-d4, because this species corresponds to deuteration at the α- and β-carbon as taught by Schneider et al. for improving metabolic stability of dopamine. One of ordinary skill in the art would have had a reasonable expectation of success to substitute dopamine as taught by ‘629B2 and Carr et al. with deuterated dopamine in view of Schneider et al. because it is known in the art that deuterated dopamine at the α- and β-carbon will improve the metabolic stability of dopamine.
Claims 57, 59 – 61 and 65 – 67 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 - 21 of U.S. Patent No. 11890266B2 in view of Carr et al. (University of Utah Health Sciences Center, 2017, cited in the previous Office Action) and Zhou et al. (Progress in Retinal and Eye Research, 2017, Vol. 61, page 60 – 71, Reference included with PTO-892).
c. Regarding claims 57, 59 – 61 and 65 – 67, ‘266B2 teaches a method of inhibiting the progression or development of a visual disorder in a subject (claim 16), wherein the visual disorder is myopia (claims 17 – 18), comprising administering a pharmaceutical ocular composition, comprising levodopa, a muscarinic acetylcholine receptor antagonist, and antioxidant, and an aqueous carrier (claim 1). The muscarinic acetylcholine receptor antagonist is selected from the group consisting of atropine, pirenzepine, himbacine, hyoscine, cyclopentolate, ipratropium, oxitropium, tropicamide, oxybutynin, tolterodine, diphenhydramine, dicycloverine, flavoxate, tiotropium, trihexyphenidyl, solifenacin, darifenacin, benzatropine, mebeverine, procyclidine, aclidinium, and salts and combinations thereof (claim 12). The antioxidant is selected from the group consisting of ascorbic acid, phenolic acids, sorbic acid, sodium bisulfate, sodium metabisulfite, acetyl cysteine, sodium thiosulfate, ethylene diamine tetraacetic acid, sodium nitrite, ascorbyl stearate, ascorbyl palmitate, alpha-thioglycerol, erythorbic acid, cysteine hydrochloride, citric acid, tocopherol or vitamin E, tocopherol acetate, dibutylhydroxytoluene, soybean lecithin, sodium thioglycolate, butylhydroxyanisole, propyl gallate, uric acid, melatonin, thiourea, and salts and combinations thereof (claim 2) and the aqueous carrier is selected from the group consisting of saline, water, aqueous buffer, an aqueous solution comprising water and a miscible solvent, and combinations thereof (claim 13). The composition is formulated for topical administration to the eye (claim 15). ‘266B2 further teaches that the composition may further comprises a GABA receptor antagonist (claim 10), wherein the GABA receptor antagonist is selected from the group consisting of bicuculline, flumazenil, gabazine, phenylenetetrazol, (1,2,5,6-tetra hydropyridin-4-yl) methylphosphinic acid, (3-aminopropyl)(cyclohexylmethyl)phosphinic acid, and salts and combinations thereof (claim 11).
However, ‘266B2 does not teach the composition comprising dopamine. ‘266B2 does not teach the composition is formulated for penetration of dopamine through corneal epithelium.
Carr et al. teaches that myopia is the most common refractive vision disorder in children, and the underlying biological cause of myopia is still unknown (Abstract, para. 1 – 2). However, Carr et al. states that there is strong evidence that dopamine is a very important molecule in myopia-inhibition and regulation of eye growth based on the studies conducted (page 18, para. 3).
Zhou et al. teach that local administration of APO and dopamine by eye drops may achieve therapeutic effects on myopia with reduced systemic side effects (page 67, Left Col., para. 1).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to substitute levodopa as taught by ‘266B2 with dopamine in view of Carr et al., as described above, because it is obvious to substitute the composition for the same purpose to achieve predictable results. One would have been motivated to simply use dopamine with the eye drop formulation that has an enhanced penetration, instead of the precursor, in the treatment of myopia. ‘266B2 also does not explicitly disclose the order of administering dopamine and atropine. However, ‘266B2 discloses that the composition is administered in the form of an eye drop and this implies that the two active ingredients will be administered together in the form of an eye drop. As Zhou et al. teach that dopamine may be formulated as eye drops and will achieve therapeutic effects on myopia, one of ordinary skill in the art would have expected that the dopamine in eye drop formulation would penetrate the corneal epithelium upon topical administration as such penetration is necessary for dopamine to reach ocular tissue and produce the therapeutic effect on myopia. Therefore, one of skill in the art would have a reasonable expectation of success to substitute levodopa as taught by ‘266B2 with dopamine taught by Carr et al. to treat myopia as ‘266B2 teaches all the limitations and Carr et al. teaches that dopamine is important for myopia-inhibition.
Claims 68, 70, 72, 74 – 76, 80 – 81, and 83 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 - 20 of U.S. Patent No. 1 - 21 of U.S. Patent No. 11890266B2 in view of Carr et al. (University of Utah Health Sciences Center, 2017, cited in the previous Office Action) and Zhou et al. (Progress in Retinal and Eye Research, 2017, Vol. 61, page 60 – 71, Reference included with PTO-892), as applied to claims 57, 59 – 61 and 65 – 67 above, and further in view of Schneider et al. (British Journal of Clinical Pharmacology, August 2018, Vol. 84, Issue 10, page 2422 – 2432, Reference included with PTO-892).
d. Regarding claims 68, 70, 72, 74 – 76, 80 – 81, and 83, ‘266B2 teaches the limitations discussed above.
However, these references do not teach the method of inhibiting myopia using the composition comprising deuterated dopamine.
Schneider et al. teach the structure of dopamine:
PNG
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85
142
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,
wherein the * represents deuterated positions (page 2424, Figure 1). Animal studies show that deuteration at α- and β-carbon slows down the breakdown of deuterated dopamine by monoamine oxidase and dopamine β-hydroxylase (page 2423, para. 3).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to substitute dopamine as taught by ‘266B2 and Carr et al. with deuterated dopamine in view of Schneider et al. because Schneider et al. teach that deuteration of dopamine at α- and β-carbon is known to slow metabolism or breakdown. One would have been motivated to substitute dopamine as taught by ‘266B2 and Carr et al. with deuterated dopamine in view of Schneider et al. because Schneider et al. teach that such deuteration slows metabolic breakdown of dopamine, thereby improving metabolic stability of dopamine. One would have performed routine experimentation to discover the number of deuteration on α- and β-carbon for the optimal metabolic stability. For claim 70, Schneider et al. teach that * represents deuterated positions in dopamine and further teach that deuteration at α- and β-carbon slows metabolic breakdown of dopamine. It would have been obvious for one of ordinary skill in the art to select dopamine deuterated at the α- and β-carbon, including dopamine-1,1,2,2-d4, because this species corresponds to deuteration at the α- and β-carbon as taught by Schneider et al. for improving metabolic stability of dopamine. One of ordinary skill in the art would have had a reasonable expectation of success to substitute dopamine as taught by ‘266B2 and Carr et al. with deuterated dopamine in view of Schneider et al. because it is known in the art that deuterated dopamine at the α- and β-carbon will improve the metabolic stability of dopamine.
Responses to Applicant’s Remarks:
Applicant’s Remarks, filed February 6, 2025, have been fully considered and are found to be not persuasive.
Regarding the ‘629B2 and Carr et al., Applicant argues that Carr et al. discuss administration of dopamine intravitreally and a skilled artisan would expect that dopamine is unlikely to penetrate to the posterior segment of the eye. There is nothing in ‘629B2 that teach or suggest levodopa and dopamine would have the same ocular permeability. In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., penetration of dopamine to the posterior segment of the eye) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Moreover, the substitution of levodopa with dopamine is based on simple substitution of one known element for another to obtain predictable results, which is a composition that is used to treat myopia. Applicant argues that neither Timmins nor Masters et al. teach or suggest the penetration of deuterated dopamine to the posterior segment of the eye and neither Timmins nor Masters et al. teach of suggest the beneficial pharmaceutical effects of deuterated dopamine. The argument is moot because Timmins and Masters et al. are no longer included in the new rejection. The combination of ‘629B2, Carr et al., and Schneider et al. renders the claimed invention obvious because ‘629B2 teaches a method for inhibiting myopia using a composition comprising levodopa, Carr et al. teach that dopamine exhibits inhibitory activity on myopia, and Schneider et la. teach that deuterated dopamine improves metabolic stability.
Regarding ‘266B2, Applicant argues that ’266B2 does not teach a composition comprising dopamine, and the composition is formulated for the penetration of dopamine through the corneal epithelium or topically administering deuterated dopamine for the treatment of myopia. However, this argument is not persuasive because ‘266B2 is relied upon for the teachings of a method for treating myopia using a composition comprising levodopa, which is a precursor of dopamine. Carr et al. provide the fact that dopamine exhibits inhibitory activity on myopia and Zhou et al. teach that dopamine formulated as eye drop will achieve therapeutic effects on myopia with reduced systemic adverse effects. The combination of references teach and suggest that dopamine may be formulated as eye drop, which penetrates through corneal epithelium, to treat myopia.
Regarding Carr et al., Applicant argues that Carr et al. only discuss administration of dopamine intravitreally. Regarding Ellis and Virno et al., Applicant argues that the ordinary skilled artisan would expected that dopamine is unlikely to penetrate to the posterior segment of the eye. Regarding ‘266B2, Applicant argues that ‘266B2 does not teach dopamine or deuterated dopamine would have the same ocular permeability.
Regarding Agarwal, Applicant argues that the skilled artisan would be motivated not to include BAK to minimize the toxicity of the formulation.
Regarding Pramar, Applicant argues that Pramar does not describe any use of dopamine or deuterated dopamine, but merely describes ophthalmic solutions generally. The skilled artisan would not be motivated to combine either Pramar or Agarwal with Carr et al., Ellis, and Virno et al. because neither Pramar nor Agarwal rectify the deficiency.
Applicant argues that neither Timmins nor Masters et al. teach or suggest the penetration of deuterated dopamine to the posterior segment of the eye and neither Timmins nor Masters et al. teach of suggest the beneficial pharmaceutical effects of deuterated dopamine.
Regarding the Declaration, Professor Morgan notes that the instant application directly addresses the issue of topical ocular administration with the aim of applying the composition to the sites of action within the eye that are relevant for the control of myopia whilst minimizing extra-ocular actions and the present invention overcomes the problems with topical administration and is found to be capable of penetrating the corneal epithelium to the posterior segment of the eye.
However, these arguments are moot because the previous rejections have been withdrawn. The new rejection is relied upon the combination of ‘266B2, Carr et al., Zhou et al., and Schneider et al. ‘266B2 teaches a method for treating myopia using a composition comprising levodopa, which is the precursor of dopamine. Carr et al. teach that dopamine is capable of inhibiting myopia. Zhou et al. teach that local administration of dopamine by eye drop may achieve therapeutic effect on myopia with reduced systemic side effects. Schneider et al. teach that deuterated dopamine at the α- and β-carbon improve metabolic stability. The combination of these references teach the limitations of the claimed method, and therefore, render the claims obvious. Moreover, Zhou et al. explicitly teaches that local administration of dopamine eye drop may achieve therapeutic effect on myopia, thereby suggesting that topically administered dopamine is capable of reaching relevant ocular tissues. Accordingly, The Declaration is not sufficient to establish that penetration of dopamine to posterior segment would have been unexpected, or that such penetration is contrary to the teachings of Zhou et al.
Conclusion
No claim is found to be allowable.
Applicant's amendment necessitated the modified / 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.
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/H.Y.L./Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693