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 .
Status of the Claims
Claims 2-3 8, 10-12, 18, 20, and 26 have been cancelled in a previous communication. Claims 1, 4-7,9,13-17,19 and 21-25 are pending and claim 25 stands withdrawn.
Claims 1, 4-7,9,13-17,19, and 21-24 are currently under examination.
All rejections not reiterated have been withdrawn.
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, 4-7, 9, 23-24 are rejected under 35 U.S.C. 103 as being unpatentable over Gan et al. (WO1994008602A1, Published 04/28/1994) in view of Salamone et al. (CZ326499A3, Published 05/17/2005) further in view of Coroneo (WO2020186293A1, Published 09/24/2020).
Applicant’s invention
The claims are drawn to an ophthalmic pharmaceutical composition, the composition comprising: a first mydriatic compound, wherein the first mydriatic compound comprises epinephrine having a concentration form about 0.01% (w/v) to about 0.05% (w/v), a first pain-relieving compound, a dye, and a pharmaceutically acceptable carrier consisting of water (H2O).
Determination of the scope and the content of the prior art
(MPEP §2141.01)
Regarding claim 1, Gan teaches an improved pharmaceutical composition useful in ophthalmic surgery wherein the composition includes a mydriatic agent, such as epinephrine in an acidic solution (abstract). Gan also teaches in example 1 part II, dissolving epinephrine in water (page 14, lines 8-9), wherein epinephrine is in the concentration amount of 0.0025-10% (w/v)(page 15, example 2).
Regarding claim 24, Gan teaches specific advantages of the composition of the present invention include elimination of chemical preservatives, such as sulfites (page 8, lines 9-12).
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
Gan does not teach a first pain-relieving compound, and a dye (instant claim 1); wherein the first pain-relieving compound comprises lidocaine, proparacaine, tetracaine, dexamethasone, fluorometholone, fluocinolone, leteprednol, difluprednate, triamcinolone, prednisolone, medrysone, or rimexolone, or pharmaceutically acceptable salts thereof (instant claim 4); wherein the dye comprises trypan blue, fluorescein, lissamine green, 4,5,6,7-tetrachloro-2',4',5',7'- tetraiodofluorescein, indocyanine green, triamcinolone acetonide, bromophenol blue, patent blue, N-[4-[[4-[(4-ethoxyphenyl)amino]phenyl][4-[ethyl[(3- sulfophenyl)methyl]amino]-2-methylphenyl]methylene]-3-methyl-2,5- cyclohexadien-1-ylidene]-N-ethyl-3-sulfo-benzenemethanaminium, or a combination thereof (instant claim 5); wherein the first pain-relieving compound has a concentration from about 0.5%(w/v) to about 2% (w/v) (instant claim 6). Gan also does not teach wherein the first pain-relieving compound comprises lidocaine (instant claim 7). Gan further does not teach wherein the lidocaine has a concentration form about 0.5% (w/v) to about 2% (w/v) (instant claim 9). Gan also does not teach wherein the dye has a concentration from about 0.01% (w/v) to about 0.25% (w/v) (instant claim 23). However, these deficiencies are cured by Salamone et al and Coroneo.
In the analogous art of ophthalmic compositions for ophthalmic surgery, Salamone teaches compositions that maintain structural integrity the anterior chamber of the eye during ophthalmic surgery while providing a lasting supply of miotic, mydriatic and/or anesthetic agent (Summary of the invention, first paragraph). Salamone also teaches the invention provides compositions comprising mydriatic agents, including but not limited to, atropine, atropine sulfate, atropine hydrochloride, atropine methyl bromide, atropine methyl nitrate, hyperduric atropine, atropine N-oxide, phenylephrine (page 4, Mydriatic agents). Salamone further teaches the invention provides compositions comprising anesthetic agents with a positive charge (cationic ammonium salts) or a potential positive charge (non-charged amino groups) such as agents including lidocaine, proparacaine, tetracaine (page 4, anesthetic agents). Salamone also teaches the concentration of the anesthetic agent may range from 1 mg / ml to 50 mg / ml (page 7, paragraph 10).
In the analogous art of ophthalmic compositions for ophthalmic surgery, Coroneo teaches provide ophthalmic compositions, and methods of using the same, to identify, mark, or stain an intraocular structure(s) or membrane(s), and/or to treat an ocular disease or condition, such as glaucoma or a cataract (paragraph [0019]). Coroneo also teaches the ophthalmic composition may comprise or consist of a single dye, wherein the single dye is Indigo Carmine, or may comprise or consist of a combination of dyes, wherein the combination of dyes comprises Indigo Carmine and at least one dye selected from the group consisting of: Trypan Blue, Brilliant Blue, Patent Blue, Indocyanine Green, and Fluorescein (paragraph [00105]). Coroneo further teaches in certain embodiments, the Indigo Carmine contained within the ophthalmic composition disclosed herein may be present in low concentrations, for example, in an amount in the range of between approximately 0.001-0.4 wt.% (paragraph [00106]), and the Trypan Blue may be present in an amount in the range of between approximately 0.001-0.1 wt.% (paragraph [00107]).
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been prima facie obvious to one of ordinary skill in the art at the time of filing to add a first pain-relieving compound to Gan’s ophthalmic composition comprising mydriatic compounds and water. Gan teaches an improved pharmaceutical composition useful in ophthalmic surgery wherein the composition includes a mydriatic agent, such as epinephrine in an acidic solution (abstract), wherein the epinephrine is dissolved in water (page 14, lines 8-9).
One would have understood in view of Salamone compositions that maintain structural integrity the anterior chamber of the eye during ophthalmic surgery while providing a lasting supply of miotic, mydriatic and/or anesthetic agent (Summary of the invention, first paragraph). Salamone also teaches it is desirable to have a system that maintains the presence of the anesthetic and at the same time reduces the performance of intracameral placement and immediate loss of the anesthetic through the aforementioned routes and desirable to provide a drug delivery system that releases the anesthetic uniformly over time and that controls the osmotic pressure associated with establishing an equilibrium state between anesthetic ions and ions existing in ocular fluids (page 3, paragraph 7). Salamone further teaches the invention provides compositions comprising anesthetic agents with a positive charge (cationic ammonium salts) or a potential positive charge (non-charged amino groups) such as agents including lidocaine, proparacaine, tetracaine (page 4, anesthetic agents). It would have been obvious to one of ordinary skill in the art to add a first pain-relieving compound to Gan’s ophthalmic composition comprising mydriatic compounds and water because Gan teaches the combination of epinephrine and water for ophthalmic surgery and Salamone teaches compositions that maintain structural integrity the anterior chamber of the eye during ophthalmic surgery that maintains the presence of the anesthetic and at the same time reduces the performance of intracameral placement and immediate loss of the anesthetic through the aforementioned routes and desirable to provide a drug delivery system that releases the anesthetic uniformly over time and that controls the osmotic pressure associated with establishing an equilibrium state between anesthetic ions and ions existing in ocular fluids (page 3, paragraph 7) by using compositions comprising anesthetic agents with a positive charge (cationic ammonium salts) or a potential positive charge (non-charged amino groups) such as agents including lidocaine, proparacaine, tetracaine (page 4, anesthetic agents).
It would have been prima facie obvious to one of ordinary skill in the art at the time of filing to add a dye to Gan’s ophthalmic composition comprising mydriatic compounds and water. Gan teaches An improved pharmaceutical composition useful in ophthalmic surgery wherein the composition includes a mydriatic agent, such as epinephrine in an acidic solution (abstract), wherein the epinephrine is dissolved in water (page 14, lines 8-9). One would have understood in view of Coroneo ophthalmic compositions, and methods of using the same, to identify, mark, or stain an intraocular structure(s) or membrane(s), and/or to treat an ocular disease or condition, such as glaucoma or a cataract (paragraph [0019]), wherein he method of treating, disclosed herein, the method includes an ocular surgery, or the ocular surgery is, selected from the group consisting of: glaucoma surgery, minimally invasive glaucoma surgery (MIGS), cataract surgery, retinal surgery, lens replacement surgery, surgery to treat ocular trauma, refractive lensectomy, corneal surgery (paragraph [0049]). Coroneo also teaches the ophthalmic composition may comprise or consist of a single dye, wherein the single dye is Indigo Carmine, or may comprise or consist of a combination of dyes, wherein the combination of dyes comprises Indigo Carmine and at least one dye selected from the group consisting of: Trypan Blue, Brilliant Blue, Patent Blue, Indocyanine Green, and Fluorescein (paragraph [00105]). It would have been obvious to one of ordinary skill in the art to add a dye to Gan’s ophthalmic composition comprising mydriatic compounds and water because Gan teaches the combination of epinephrine and water for ophthalmic surgery and Coroneo teaches ophthalmic compositions, and methods of using the same, to identify, mark, or stain an intraocular structure(s) or membrane(s), and/or to treat an ocular disease or condition, such as glaucoma or a cataract (paragraph [0019]), wherein he method of treating, disclosed herein, the method includes an ocular surgery, or the ocular surgery is, selected from the group consisting of: glaucoma surgery, minimally invasive glaucoma surgery (MIGS), cataract surgery, retinal surgery, lens replacement surgery, surgery to treat ocular trauma, refractive lensectomy, corneal surgery (paragraph [0049]).
With regards to claims 6, and 9 wherein the first pain-relieving compound has a concentration from about 0.5% (w/v) to about 2% (w/v); and wherein the lidocaine has a concentration from about 0.5% (w/v) to about 2% (w/v), it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to optimize the concentration of the first pain-relieving compound which is lidocaine. Salamone teaches the concentration of the anesthetic agent may range from 1 mg / ml to 50 mg / ml (page 7, paragraph 10). It would have been obvious to one of ordinary skill in the art to use the amount of Salamone as a starting point for routine optimization of the concentration of lidocaine for the desired results to have an anesthetic effect. Where 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, 105 USPQ 233 (CCPA 1955). See MPEP 2144.05 (II)(A). In addition, according to the MPEP, “It is to be presumed also that skilled workers would as a matter of course, if they do not immediately obtain desired results, make certain experiments and adaptations, within the skill of the competent worker.” (MPEP 716.07).
Claims 13-17, 19, and 21-22 are rejected under 35 U.S.C. 103 as being unpatentable over Gan et al. (WO1994008602A1, Published 04/28/1994) in view of Salamone et al. (CZ326499A3, Published 05/17/2005) further in view of Coroneo (WO2020186293A1, Published 09/24/2020) further in view of Grob et al. (Clin Ophthalmol. Published 2014 Jul 3;8:1281-1289).
Applicant’s invention
Gan, Salamone, and Coroneo render obvious all the limitations of claim 1. Applicant’s claim 13 further adds the limitation wherein the composition of claim 1 further comprises a second mydriatic compound and a second pain-relieving compound. Applicant’s claim 14 further adds the limitation wherein the second mydriatic compound comprises epinephrine, phenylephrine, tropicamide, atropine, brimonidine, cyclopentolate, homatropine, 4-hydroxyamphetamine, or scopolamine, or pharmaceutically acceptable salts thereof. Applicant’s claim 15 further adds the limitation wherein the second pain-relieving compound comprises lidocaine, proparacaine, tetracaine, dexamethasone, fluorometholone, fluocinolone, loteprednol, loteprednol, difluprednate, triamcinolone, prednisolone, medrysone, or rimexolone, or pharmaceutically acceptable salts thereof. Applicant’s claim 16 further adds the limitation wherein the second pain-relieving compound is a non-steroidal anti-inflammatory drug. Applicant’s claim 17 further adds the limitation wherein in the first mydriatic compound is tropicamide, the second mydriatic compound is phenylephrine, the first pain- relieving compound is lidocaine, and the second pain-relieving compound is diclofenac. Applicant’s claim 19 further adds wherein the phenylephrine has a concentration from about 0.01 % (w/v) to about 2% (w/v). Applicant’s claim 21 further adds wherein diclofenac has a concentration from about 0.01 % (w/v) to about 0.5% (w/v). Applicant’s claim 22 further adds wherein the concentration of the non- steroidal anti-inflammatory drug is from about 0.1% (w/v) to about 0.5% (w/v).
Determination of the scope and the content of the prior art
(MPEP §2141.01)
Regarding claims 13-14, 17, and 19, Gan teaches An improved pharmaceutical composition useful in ophthalmic surgery wherein the composition includes a mydriatic agent, such as epinephrine in an acidic solution (abstract). Gan also teaches in example 1 part II, dissolving epinephrine in water (page 14, lines 8-9), wherein epinephrine is in the concentration amount of 0.0025-10% (w/v)(page 15, example 2). Gan further teaches the irrigating compositions of the present invention contain one or more agents to produce and maintain mydriasis during an intraocular surgical procedure, wherein such agents are referred to herein as mydriatic agents, wherein the preferred compounds include epinephrine; phenylephrine; dipivalyl epinephrine; norepinephrine; isoproterenol; and the pivaloyloxy and phenylacetyloxy ester derivatives of epinephrine and norepinephrine (Pages 8-9, Description of Preferred Embodiments).
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
Gan does not teach a second pain-relieving compound (instant claim 13); wherein the second pain-relieving compound comprises lidocaine, proparacaine, tetracaine, dexamethasone, fluorometholone, fluocinolone, loteprednol, difluprednate, triamcinolone, prednisolone, medrysone, or rimexolone, or pharmaceutically acceptable salts thereof (instant claim 15); wherein the second pain-relieving compound is a non-steroidal anti-inflammatory drug (instant claim 16); wherein the second pain-relieving compound is diclofenac (instant claim 17); wherein the diclofenac has a concentration from about 001%(w/v) to about 0.5%(w/v) (claim 21); and wherein the concentration of the non-steroidal anti-inflammatory drug is form about 0.1% (w/v) (instant claim 22). However these deficiencies are cured by Salamone et al and Grob et al.
In the analogous art of ophthalmic compositions for ophthalmic surgery, Salamone teaches compositions that maintain structural integrity the anterior chamber of the eye during ophthalmic surgery while providing a lasting supply of miotic, mydriatic and/or anesthetic agent (Summary of the invention, first paragraph). Salamone also teaches the invention provides compositions comprising mydriatic agents, including but not limited to, atropine, atropine sulfate, atropine hydrochloride, atropine methyl bromide, atropine methyl nitrate, hyperduric atropine, atropine N-oxide, phenylephrine (page 4, Mydriatic agents). Salamone further teaches The invention provides compositions comprising anesthetic agents with a positive charge (cationic ammonium salts) or a potential positive charge (non-charged amino groups) such as agents including lidocaine, proparacaine, tetracaine (page 4, anesthetic agents). Salamone also teaches the concentration of the anesthetic agent may range from 1 mg / ml to 50 mg / ml (page 7, paragraph 10).
In the analogous art of cataract surgery, Grob teaches the maintenance of mydriasis and the control of postoperative pain and inflammation are critical to the safety and success of cataract and intraocular lens replacement surgery. Appropriate mydriasis is usually achieved by topical and/or intracameral administration of anticholinergic agents, sympathomimetic agents, or both, with the most commonly used being cyclopentolate, tropicamide, and phenylephrine. Ocular inflammation is common after cataract surgery. Topical steroids and nonsteroidal anti-inflammatory drugs (NSAID) are widely used because they have been proved effective to control postsurgical inflammation and decrease pain. Topical nonsteroidal anti-inflammatory drugs have also been shown to help maintain dilation. However, use of multiple preoperative drops for pupil dilation, inflammation, and pain control have been shown to be time consuming, resulting in delays to the operating room, and they cause dissatisfaction among perioperative personnel; their use can also be associated with systemic side effects. Therefore, ophthalmologists have been in search of new options to streamline this process. A new combination of ketorolac, an anti-inflammatory agent, and phenylephrine, a mydriatic agent has recently been designed to maintain intraoperative mydriasis and to reduce postoperative pain and irritation from intraocular lens replacement surgery (abstract). Grob further teaches diclofenac 1% in table 2 as an available nonsteroidal anti-inflammatory drug (NSAID) used to minimize inflammation related to cataract surgery (Table 2).
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been prima facie obvious to one of ordinary skill in the art at the time of filing to add a second pain-relieving compound to Gan’s ophthalmic composition comprising mydriatic compounds and water. Gan teaches An improved pharmaceutical composition useful in ophthalmic surgery wherein the composition includes a mydriatic agent, such as epinephrine in an acidic solution (abstract), wherein the epinephrine is dissolved in water (page 14, lines 8-9).
One would have understood in view of Salamone compositions that maintain structural integrity the anterior chamber of the eye during ophthalmic surgery while providing a lasting supply of miotic, mydriatic and/or anesthetic agent (Summary of the invention, first paragraph). Salamone also teaches it is desirable to have a system that maintains the presence of the anesthetic and at the same time reduces the performance of intracameral placement and immediate loss of the anesthetic through the aforementioned routes and desirable to provide a drug delivery system that releases the anesthetic uniformly over time and that controls the osmotic pressure associated with establishing an equilibrium state between anesthetic ions and ions existing in ocular fluids (page 3, paragraph 7). Salamone further teaches the invention provides compositions comprising anesthetic agents with a positive charge (cationic ammonium salts) or a potential positive charge (non-charged amino groups) such as agents including lidocaine, proparacaine, tetracaine (page 4, anesthetic agents). It would have been obvious to one of ordinary skill in the art to add a second pain-relieving compound to Gan’s ophthalmic composition comprising mydriatic compounds and water because Gan teaches the combination of epinephrine and water for ophthalmic surgery and Salamone teaches compositions that maintain structural integrity the anterior chamber of the eye during ophthalmic surgery that maintains the presence of the anesthetic and at the same time reduces the performance of intracameral placement and immediate loss of the anesthetic through the aforementioned routes and desirable to provide a drug delivery system that releases the anesthetic uniformly over time and that controls the osmotic pressure associated with establishing an equilibrium state between anesthetic ions and ions existing in ocular fluids (page 3, paragraph 7) by using compositions comprising anesthetic agents with a positive charge (cationic ammonium salts) or a potential positive charge (non-charged amino groups) such as agents including lidocaine, proparacaine, tetracaine (page 4, anesthetic agents).
It would have been prima facie obvious to one of ordinary skill in the art at the time of filing to add a second pain-relieving compound which can be a non-steroidal anti-inflammatory drug such as diclofenac in Gan’s ophthalmic composition comprising mydriatic compounds and water. Gan teaches An improved pharmaceutical composition useful in ophthalmic surgery wherein the composition includes a mydriatic agent, such as epinephrine in an acidic solution (abstract), wherein the epinephrine is dissolved in water (page 14, lines 8-9). One would have understood in view of Grob that the maintenance of mydriasis and the control of postoperative pain and inflammation are critical to the safety and success of cataract and intraocular lens replacement surgery, wherein topical steroids and nonsteroidal anti-inflammatory drugs (NSAID) are widely used because they have been proved effective to control postsurgical inflammation and decrease pain and have also been shown to help maintain dilation. A new combination of ketorolac, an anti-inflammatory agent, and phenylephrine, a mydriatic agent has recently been designed to maintain intraoperative mydriasis and to reduce postoperative pain and irritation from intraocular lens replacement surgery (abstract). It would have been obvious to one of ordinary skill in the art to add a second pain-relieving compound which can be a non-steroidal anti-inflammatory drug such as diclofenac in Gan’s ophthalmic composition comprising mydriatic compounds and water because Gan teaches the combination of epinephrine which is mydriatic agent and water for ophthalmic surgery and Grob teaches the combination of an anti-inflammatory agent, and a mydriatic agent is used because Appropriate mydriasis and inflammatory control during intraocular lens exchange surgery is key to a successful surgical outcome, therefore a myriad of topical and/or intracameral agents have been used to dilate the pupil and to control postoperative pain and inflammation (conclusion section).
With regards to the limitation on amounts of each substances recited in instant claims 19 and 21-22, Gan teaches wherein epinephrine is in the concentration amount of 0.0025-10% (w/v)(page 15, example 2) and Grob teaches diclofenac as 1%, therefore it would have been prima facie obvious to one of ordinary skill in the art to figure out optimal concentrations for any given mydriatic compound to have a dilating effect and anti-inflammatory drug to have an anti-inflammatory effect. Where 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, 105 USPQ 233 (CCPA 1955). See MPEP 2144.05 (II)(A). In addition, according to the MPEP, “It is to be presumed also that skilled workers would as a matter of course, if they do not immediately obtain desired results, make certain experiments and adaptations, within the skill of the competent worker.” (MPEP 716.07).
Response to Arguments
Applicant's arguments filed 04/13/2026 have been fully considered but they are not persuasive.
On pages 5-6 of Applicants remarks, Applicants argue that the Office has not properly established why a person skilled in the art would be motivated to combine the references to arrive at the claimed invention.
This statement ignores the reasons expressly set forth in the rejection and therefore is not persuasive.
On page 7 of Applicants remarks, Applicants argue that Coroneo used alone would not treat glaucoma or cataracts as the office appears to suggest and that Coroneo specifies that the dye compositions escribed therein assist in identifying ocular structures or membranes. Applicants further argue that Coroneo does not include any other active ingredient, therefore there is no reason as to why a skilled artisan would be motivated to include a dye in the composition of Gan.
In response to applicant's arguments against the references individually, 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). Furthermore, In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, Gan teaches an improved pharmaceutical composition useful in ophthalmic surgery wherein the composition includes a mydriatic agent, such as epinephrine in an acidic solution (abstract), wherein the epinephrine is dissolved in water (page 14, lines 8-9). One would have understood in view of Coroneo ophthalmic compositions, and methods of using the same, to identify, mark, or stain an intraocular structure(s) or membrane(s), and/or to treat an ocular disease or condition, such as glaucoma or a cataract (paragraph [0019]). Coroneo also teaches the ophthalmic composition may comprise or consist of a single dye, wherein the single dye is Indigo Carmine, or may comprise or consist of a combination of dyes, wherein the combination of dyes comprises Indigo Carmine and at least one dye selected from the group consisting of: Trypan Blue, Brilliant Blue, Patent Blue, Indocyanine Green, and Fluorescein (paragraph [00105]). It would have been obvious to one of ordinary skill in the art to add a dye to Gan’s ophthalmic composition comprising mydriatic compounds and water because Gan teaches the combination of epinephrine and water for ophthalmic surgery and Coroneo teaches ophthalmic compositions, and methods of using the same, to identify, mark, or stain an intraocular structure(s) or membrane(s), and/or to treat an ocular disease or condition, such as glaucoma or a cataract (paragraph [0019]), wherein the method of treating, includes ocular surgery (paragraph [0049]). Both compositions were known for facilitating visualization of ocular structures during eye surgery. See further discussion below.
On pages 8-9 of Applicants remarks, Applicants argue that the person having ordinary skill in the art would have no motivation or reasonable expectation of success in arriving at the claimed compositions when specifically epinephrine is used because Gan notes the difficulty of formulating with epinephrine, therefore the skilled artisan would be hesitant to combine epinephrine with a dye given the instability of epinephrine noted by Gan. Applicants further argue that the Office’s assertions that the skilled artisan would be motivated to combine the compound of Gan with the dye of Coroneo amounts to a conclusion that it would be within the ordinary skill of the art at time the application was filed, but the mere fact that all aspects of the claimed invention were individually known is the art is not sufficient to establish a prima facie case of obviousness without some objective reason to combine the teaching of the references.
These arguments are not persuasive. The examiner considers the reasonable expectation of success prong of the obviousness analysis to have been met for the same reasons that Applicants claims are enabled under 112(a). The extent of testing required to determine whether adding a dye to Gan’s formulation is not so extreme that one of ordinary skill, a Ph.D. level scientist in pharmaceutical formulations would have lacked reasonable expectation of success in achieving an operable formulation containing both substances. The Examiner also points out that Gan teaches that epinephrine is relatively stable in an acidic environment wherein the pH from about 3 to 5 is preferred. Therefore a two part product is preferred, wherein the first part is an acidic solution containing one or more mydriatic agents and the second part is a buffered solution to be combined for the use of ocular surgery (page 9, lines 16-30). Moreover, one of ordinary skill in the art would have been motivated to include a dye such as those disclosed by Coroneo in order to accurately locate the position and identify ocular structures within the instilled eye (paragraph [0018]). The skilled artisan would have had a reasonable expectation of success because Gan provides ample instruction on how to stabilize epinephrine and it would merely require routine testing for compatibly of the dyes in combination with the epinephrine. The examiner considers this type of confirmation that a formulation remains stable to be routine for one having ordinary skill at the time of filing, e.g. an individual with a Ph.D. in formulations science. Conclusive proof of efficacy is not required to show a reasonable expectation of success. OS/ Pharm., LLC v. Apotex Inc., 939 F.3d 1375, 1385, 2019 USPQ2d 379681 (Fed. Cir. 2019) ("To be clear, we do not hold today that efficacy data is always required for a reasonable expectation of success. Nor are we requiring ‘absolute predictability of success.’") See also: MPEP2143(I)(B): This is not a situation where the rejection is a statement that it would have been “obvious to try” without more. Here there was a reasonable expectation of success. “Obviousness does not require absolute predictability of success.” Id. at 903, 7 USPQ2d at 1681."
With regards to Applicants arguments that the Office’s assertions that the skilled artisan would be motivated to combine the compound of Gan with the dye of Coroneo amounts to a conclusion that it would be within the ordinary skill of the art at time the application was filed, but the mere fact that all aspects of the claimed invention were individually known is the art is not sufficient to establish a prima facie case of obviousness without some objective reason to combine the teaching of the references, the Examiner points out that Gan teaches epinephrine is frequently used in the field of ophthalmology to effect dilation of the pupil (i.e., mydriasis). The use of this drug is particularly prevalent in ophthalmic surgical procedures, since dilation of the pupil is frequently necessary in order to increase surgeons' ability to see inside the eye with the aid of a microscope. More specifically, dilation of the pupil during intraocular surgery is necessary to allow visualization and manipulation of tissues which lie behind the plane of the iris, including the lens, retina, and all ocular structures in the posterior segment (page ,). Coroneo teaches the identification of ocular structure(s) via instillation of an ophthalmic dye, such as Indigo Carmine, Trypan Blue, or another ophthalmic dye, whereby the ophthalmic dye facilitates accurately locating the position and identifying ocular structures within the instilled eye. For example, via staining of the ocular structure or by a collection or concentration of the ophthalmic dye in, about, and/or on the ocular structure, thereby facilitating visual identification of the ocular structures. Visual identification of the ocular structures in the instilled eye may be accomplished with or without the assistance of a magnifying powered inspection of the instilled eye (e.g., with a microscope or magnified lens) (paragraph [0018]). Therefore, as taught by Gan and Coroneo, epinephrine and dye are both known for the purpose of visualization of ocular structures in ophthalmic surgeries. See MPEP 2144.06 (I). One having ordinary skill in the art would have understood that visualization of ocular structures would have been improved by having both the dye and epinephrine.
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, 4-7, 9, 13-17, 19, and 21-24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-19 of copending Application No. 18/266491 in view of Gan et al. (WO1994008602A1, Published 04/28/1994) further in view of Coroneo (WO2020186293A1, Published 09/24/2020).
Although the claims at issue are not identical, they are not patentably distinct from each other because the patent claims render obvious the instant claims.
Inter alia the claims of ‘491 application embraces a pharmaceutical composition, comprising: (a) a therapeutically effective quantity of two mydriatic compounds; (b) a therapeutically effective quantity of at least one non-steroid anti-inflammatory drug wherein the composition is free of sulfites and preservatives. The two mydriatic compounds are selected from the group of consisting of phenylephrine, tropicamide, brimonidine, cyclopentolate, homatropine, scopolamine; and pharmaceutically acceptable salts thereof. Wherein the at least one anesthetic is selected from the group consisting of lidocaine, proparacaine, tetracaine and the at least one non-steroid anti-inflammatory drug is selected from diclofenac. Although the concentrations of phenylephrine, tropicamide, lidocaine, and diclofenac is not taught in the ‘491 application, however it is obvious to optimize the amount that is concentrations for any given mydriatic compound to have a dilating effect, anti-inflammatory drug to have an anti-inflammatory effect, pain reliever to have a pain-relieving affect, and dye to have a diagnostic effect of the retina and iris. Where 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, 105 USPQ 233 (CCPA 1955). In addition, according to the MPEP, “It is to be presumed also that skilled workers would as a matter of course, if they do not immediately obtain desired results, make certain experiments and adaptations, within the skill of the competent worker.” (MPEP 716.07). The claims do not recite epinephrine. Gan teaches an improved pharmaceutical composition useful in ophthalmic surgery wherein the composition includes a mydriatic agent, such as epinephrine in an acidic solution (abstract). Gan also teaches in example 1 part II, dissolving epinephrine in water (page 14, lines 8-9), wherein epinephrine is in the concentration amount of 0.0025-10% (w/v)(page 15, example 2). Gan further teaches the irrigating compositions of the present invention contain one or more agents to produce and maintain mydriasis during an intraocular surgical procedure, wherein such agents are referred to herein as mydriatic agents, wherein the preferred compounds include epinephrine; phenylephrine; dipivalyl epinephrine; norepinephrine; isoproterenol; and the pivaloyloxy and phenylacetyloxy ester derivatives of epinephrine and norepinephrine (Pages 8-9, Description of Preferred Embodiments). The claimed mydriatic compound in the ‘491 application is phenylephrine. Phenylephrine and epinephrine are known to serve the same purpose, so it was obvious to add epinephrine to the composition because it was known for the same purpose as the mydriatic agents disclosed by ‘491 application, See MPEP 2144.06.
With regard to the limitations of instant claims 1, 5, and 23 wherein there is a dye in the composition and the dye comprises trypan blue, fluorescein, lissamine green, rose Bengal, indocyanine green, triamcinolone acetonide, bromophenol blue, patent blue brilliant blue B (acid blue), or a combination thereof and its concentrations in the ophthalmic pharmaceutical compositions, Coroneo teaches provide ophthalmic compositions, and methods of using the same, to identify, mark, or stain an intraocular structure(s) or membrane(s), and/or to treat an ocular disease or condition, such as glaucoma or a cataract (paragraph [0019]). Coroneo also teaches the ophthalmic composition may comprise or consist of a single dye, wherein the single dye is Indigo Carmine, or may comprise or consist of a combination of dyes, wherein the combination of dyes comprises Indigo Carmine and at least one dye selected from the group consisting of: Trypan Blue, Brilliant Blue, Patent Blue, Indocyanine Green, and Fluorescein (paragraph [00105]). Coroneo further teaches In certain embodiments, the Indigo Carmine contained within the ophthalmic composition disclosed herein may be present in low concentrations, for example, in an amount in the range of between approximately 0.001-0.4 wt.% (paragraph [00106]), and the Trypan Blue may be present in an amount in the range of between approximately 0.001-0.1 wt.% (paragraph [00107]). One of ordinary skill in the art would have been motivated to include a dye such as those disclosed by Coroneo in the ‘491 invention in order to add the ability to diagnose various ocular pathologies. The skilled artisan would have had a reasonable expectation of success because Coroneo discloses the dyes to be useful in ophthalmic compositions.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments filed 04/13/2026 have been fully considered but they are not persuasive.
On page 10 of Applicants remarks, Applicants argue for the reasons described above with respect to the 103 obviousness rejection, nothing in Gan or Coroneo would actually motivate the skilled artisan to modify the composition of claim 1 of the ‘491 application to include the dye of Coroneo.
This argument is not persuasive to traverse the nonstatutory double patenting rejections for the same reasons explained above following the USC §103 obviousness rejection and in the response to arguments section above.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AFUA BAMFOAA BOATENG whose telephone number is (703)756-1358. The examiner can normally be reached Monday - Friday 9:00am - 5:00pm.
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AFUA BAMFOAA BOATENGExaminer, Art Unit 1617
/KATHERINE PEEBLES/Primary Examiner, Art Unit 1617
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