DETAILED ACTION
Status of the Claims
Claims 1, 4, 5, 7-10, 12, 14, 16-20, 22, 23, 25, 26, 28-31, 35, 36 and 38 are pending in the instant application. Claims 22, 23, 25, 26 and 38 have been withdrawn based upon Restriction/Election as discussed below. Claims 1, 4, 5, 7-10, 12, 14, 16-20, 28-31, 35 and 36 are being examined on the merits in the instant application.
Advisory Notice
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Restriction/Election
Applicant’s election without traverse of the following species in the reply filed on 08/06/2026 is acknowledged.
The examiner required an election of species as follows: (a) A sterile pharmaceutical formulation with specificity to each of: (i) a pharmaceutical agent, (ii) a cationic polymer, (iii) a non-ionic polymer, (iv) a pharmaceutical carrier, and (v) an anionic polymer. In reply Applicant has elected (a)(i) a pharmaceutical agent is atropine; (a)(ii) a cationic polymer is chitosan; (a)(iii) a non-ionic polymer is polyvinyl pyrrolidone; (a)(iv) a pharmaceutical carrier is water; and (a)(v) an anionic polymer is polycarbophil. The examiner is expanding the search for (a)(iii) to include poly(oxyethylene-co-oxypropylene) block copolymer (poloxamers)(instant claims 4 & 36), and (a)(v) to include polycarbophil and carbomer (instant Specification, p. 2, [0006]; p. 28, [00107]).
The requirement is deemed proper and is therefore made FINAL.
Claims 22, 23, 25, 26 and 38 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected subject matter, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 08/06/2026.
Priority
The U.S. effective filing date has been determined to be 03/07/2022, the filing date of PCT/US2022/019167.
Information Disclosure Statement
The information disclosure statements submitted on 11/18/2024, 12/16/2025 and 04/02/2026 were filed before the mailing date of the first office action on the merits. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the Examiner.
Specification
The abstract of the disclosure is objected to because the abstract is from the PCT and therefore not printed on a separate page without any other text. 37 CFR 1.72 “(b) A brief abstract of the technical disclosure in the specification must commence on a separate sheet, preferably following the claims, under the heading "Abstract" or "Abstract of the Disclosure." The sheet or sheets presenting the abstract may not include other parts of the application or other material. The abstract must be as concise as the disclosure permits, preferably not exceeding 150 words in length. The purpose of the abstract is to enable the Office and the public generally to determine quickly from a cursory inspection the nature and gist of the technical disclosure” Correction is required. See MPEP § 608.01(b).
Claim Rejections - 35 USC § 112(b)
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 1, 4, 5, 7-10, 12, 14, 16-20, 28-31, 35 and 36 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 pre-AIA the applicant regards as the invention.
Claim 1 is rejected as being indefinite because the claim recites “the clinical effect stemming from the sterile pharmaceutical composition” which is unclear because “the clinical effect stemming from the sterile pharmaceutical composition” lacks proper antecedent basis in the claim. Appropriate clarification is required. Claims 4, 5, 7-10, 12, 14, 16-20, 28-31, 35 and 36 depend from claim 1 and are rejected as inheriting and doing nothing to clarify the above discussed limitation.
Claim 18 is rejected as being indefinite because the claim recites “the pharmaceutical composition does not comprise a preservative” which is unclear because the metes and bounds of “a preservative” are unclear. For example, sodium chloride (salt) is a well-known preservative that is commonly included in compositions suitable for contacting the ocular surface. Appropriate clarification of exactly what preservatives are being excluded is required.
Claim 31 is rejected as being indefinite because the claim recites “the pharmaceutical composition is stable for at least 60 days of storage in a sealed container at a temperature of 25° (±2) and 60% (±5%) relative humidity.” where the claim term “stable” in the context of the claim is unclear. The instant Specification states that: “As used herein the term “stable” means that the sterile packaged formulation is potent and active as determined by a suitable assay on storage.” However, “a suitable assay” is not defined in a way that is exactly clear, therefore the term stable in the context of the claim is unclear. Appropriate clarification is required.
Claims 30 and 31 each recite “at a temperature of 25° (±2) and 60% (±5%) relative humidity” where the use of parentheses renders the claim unclear as to what exactly the parameters of temperature and humidity should be considered. Applicant can overcome by deleting the parentheses. The examiner also recommends the temperature should be “25° ±2°”.
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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, 5, 7-10, 12, 14, 16- 18, 20, 28-31, 35 and 36 are rejected under 35 U.S.C. 103 as being unpatentable over OSTROW (US 2018/0193326 A1; published July, 2018) in view of Berton et al. (“Stability of Ophthalmic Atropine Solutions for Child Myopia Control,” 2020, MDPI; Pharmaceutics, Vol. 12, No. 781, pp. 1-17; and Berton et al. Supplementary Materials, 8-pages).
Applicants Claims
Applicant claims a sterile pharmaceutical composition for contacting an ocular surface of a mammal, the sterile pharmaceutical composition comprising: a pharmaceutical agent, a cationic polymer, a non-ionic polymer, and a pharmaceutical carrier (instant claim 1). Applicant further claims the pharmaceutical agent is atropine in a concentration of about 0.001% w/v to about 3% w/v (claims 28-29). Applicant claims the cationic polymer comprises chitosan (instant claim 35), and the non-ionic polymer is selected from polyvinyl pyrrolidone, a poly(oxyethylene-co-oxypropylene) block copolymer (poloxamer), or a combination thereof (claims 4 & 36).
Elected Species: Applicant has elected (a)(i) a pharmaceutical agent is atropine; (a)(ii) a cationic polymer is chitosan; (a)(iii) a non-ionic polymer is polyvinyl pyrrolidone; (a)(iv) a pharmaceutical carrier is water; and (a)(v) an anionic polymer is polycarbophil. The examiner is expanding the search for (a)(iii) to include poly(oxyethylene-co-oxypropylene) block copolymer (poloxamers)(instant claims 4 & 36), and (a)(v) to include polycarbophil and carbomer (instant Specification, p. 2, [0006]; p. 28, [00107]).
Determination of the scope
and content of the prior art (MPEP 2141.01)
OSTROW teaches ophthalmic compositions (title), “the ophthalmic composition includes a low concentration of an ophthalmic agent for treatment of an ophthalmic disorder or condition; and an ophthalmically acceptable carrier, wherein the ophthalmic agent is distributed with substantial uniformity throughout the ophthalmically acceptable carrier. Further disclosed herein include an ophthalmic composition including a low concentration of an ophthalmic agent and deuterated water. Also disclosed herein are methods of arresting or preventing myopia development by administering to an eye of an individual in need thereof an effective amount of an ophthalmic composition as described herein.” (abstract).
OSTROW teaches that: “Provided herein are ophthalmic compositions. In some embodiments, disclosed herein is an ophthalmic composition, comprising from about 0.001 wt% to about 0.05 wt % of a muscarinic antagonist and deuterated water, at a pD of from about 4.2 to about 7.9.” ([0003])(instant claim 20, pD being equivalent to pH)(instant claims 1 & 17, a pharmaceutical carrier comprises water). And that: “In some embodiments, the muscarinic antagonist comprises atropine, atropine sulfate, […] In some embodiments, the muscarinic antagonist is atropine, or atropine sulfate.” ([0004])(instant claims 1, a pharmaceutical agent is atropine, in an amount of about 0.001% w/v to 3% w/v).
OSTROW teaches that: “In some embodiments, the ophthalmic composition
further comprises a buffer agent.” ([0017])(instant claim 16, pH adjusting agents). OSTROW teaches the inclusion of tonicity adjusting agents such as sodium chloride, among others ([0018] & [0178])(instant claim 12). OSTROW teaches the inclusion of stabilizers including EDTA, among others ([0138]), and antioxidants including sodium thiosulfate and sodium metabisulfite ([0140])(instant claim 14).
OSTROW teaches that: “In some embodiments, the compositions are sterilized. Included within the embodiments disclosed herein are means and processes for sterilization of a pharmaceutical composition disclosed herein for use in humans.” (instant claim 1, A sterile pharmaceutical composition).
OSTROW teaches that: “In some embodiments, the ophthalmic composition is an ophthalmic gel, and wherein the ophthalmically acceptable carrier comprises water and at least one viscosity enhancing agent. In some embodiments, the viscosity-enhancing agent is selected from […] polyoxyethylene-polyoxypropylene triblock copolymers, […] polyvinylpyrrolidone, […] chitosan […] or combinations thereof.” [emphasis added] ([0023], [0213] & [0219])(instant claim 1, a cationic polymer is chitosan; a non-ionic polymer is polyvinyl pyrrolidone; instant claim 4, one or more additional non-ionic polymers is polyoxyethylene-polyoxypropylene triblock copolymers – poloxamer). OSTROW teaches other viscosity enhancing agents compatible with the targeted ocular site include carbomer and Carbopol, among others (instant claim 5, an anionic polymer).
Ascertainment of the difference between
the prior art and the claims (MPEP 2141.02)
The difference between the rejected claims and the teachings of OSTROW is that OSTROW does not expressly teach: (1) the amounts of the anionic polymer (carbomer), cationic polymer (chitosan) and non-ionic polymer (polyvinyl pyrrolidone (instant claims 7-9); (2) the pharmaceutical composition does not comprise a preservative (instant claim 18); or (3) the stability as determined by the content of the tropic acid concentration being less than 0.01 g/mL after 180 days (6-moths) of storage at 25 °C and 60% relative humidity (instant claims 30-31).
Regarding the amounts of the amounts of the anionic polymer (carbomer), cationic polymer (chitosan) and non-ionic polymer (polyvinyl pyrrolidone), which are conventional polymer viscosity adjusting agents utilized in topical ocular formulations and would have been optimized for the same (instant claims 7-9). MPEP §2144.05(II) - Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical.
Berton et al. teaches that: “Myopia is an ophthalmic condition affecting more than 1/5th of the world population, especially children. Low-dose atropine eyedrops have been shown to limit myopia evolution during treatment. However, there are currently no commercial industrial forms available and there is little data published concerning the stability of medications prepared by compounding pharmacies. The objective of this study was to evaluate the stability of two 0.1 mg/mL atropine formulations (with and without antimicrobial preservatives) for 6 months in two different low density polyethylene (LDPE) multidose eyedroppers. Analyses used were the following: visual inspection, turbidity, chromaticity measurements, osmolality and pH measurements, atropine quantification by a stability-indicating liquid chromatography method, breakdown product research, and sterility assay. In an in-use study, atropine quantification was also performed on the drops emitted from the multidose eyedroppers. All tested parameters remained stable during the 6 months period, with atropine concentrations above 94.7% of initial concentration. A breakdown product (tropic acid) did increase slowly over time but remained well below usually admitted concentrations. Atropine concentrations remained stable during the in-use study. Both formulations of 0.1 mg/mL of atropine (with and without antimicrobial preservative) were proved to be physiochemically stable for 6 months at 25 °C when stored in LDPE bottles, with an identical microbial shelf-life.” (abstract).
Berton et al. teaches that: “In order to treat patients, hospital and compounding pharmacies could produce the desired ophthalmic solution, but the lack of long-term validated stability data severely limits their conservation period by imposing short expiration dates after preparation. […] As single-dose container technology is not readily available to compounding pharmacies, multidose eyedroppers (often in low dose polypropylene) are the most used container and therefore the most studied. However, not all of those devices possess a system allowing their content to be preservative-free, and their contents must therefore be preserved. Because 0.1 mg/mL is the concentration with currently the most data concerning safety and efficacy, the aim of this study was therefore to assess the physicochemical stability and to control the sterility of two 0.1 mg/mL atropine ophthalmic solutions (with and without an antimicrobial conservative) in two different low-density polyethylene (LDPE) multidose eyedroppers (one with a sterility-preserving technology allowing the absence of an antimicrobial preservative in the formulation and the other without such a system in order to allow choice of container depending on stability data) at 25 °C for six months in unopened eyedroppers.” (p. 2, 2nd paragraph).
Berton et al. teaches that: “The eyedroppers containing atropine were stored upwards in an ICH Q1B compliant climate chamber ([…]) at 25 °C ±2 °C and 60 ± 5% residual humidity until analysis.” (p. 3, §2.2.1, 1st paragraph). And that: “Atropine quantification was then realized in triplicate from 10 collected and pooled
drops. In between use, the bottles were stored vertically at 25 °C.” (p. 4, §2.2.2).
Berton et al. teaches that: “For both of the tested formulations, all parameters were in favour of a physicochemical stability of 6 months. No modifications of visual aspect, chromaticity, or luminance were detected. Chromaticity analyses would have helped to detect minute modifications of colour, invisible to the naked eye, but as such, the solutions remained colourless throughout the study. Turbidity analyses did not reveal the formation of any additional particles, and the pH and osmolality values also remained within specifications and were compatible with an ophthalmic administration route. Atropine concentrations also remained within specifications after 6 months of storage (maximum loss of 5.3% of initial mean concentration), thus conserving good therapeutic efficiency during the conservation period. However, they did decrease for both formulations following a linear degradation rate, leading to increasing concentrations of tropic acid which reached a maximum of 3.5 μg/mL after 6 months of storage.” (0.01 mg/mL = 10 μ/mL, and 3.5 μg/mL is less than 10 μ/mL, and therefore less than 0.01 mg/mL – Instant claims 30-31). Also, see Berton et al. Supplementary Materials, page 2 for tropic acid levels at different times (Days 8, 15, 30, 60, 90 and 180).
Berton et al. further teaches that: “It also indicates that the preservative-free formulation can be used safely with the sterility preserving device that was tested (using Novelia® caps). As antimicrobial preservatives are known to cause potential side effects, especially during long-term treatments, this information is also of high clinical value.” (p. 13, 3rd paragraph)(instant claim 18).
Regarding the limitation “wherein the duration of the clinical effect stemming from the sterile pharmaceutical composition is greater than 6 hours.”, the examiner cites Hiraoka et al.1 disclosing that: “The cycloplegic effect usually lasts for several days even after instillation of a single drop of atropine.” (p. 8, col. 2, 2nd paragraph, lines 1-2). Thus, it would have been considered an inherit property of ocular atropine eyedrops that “the clinical effect” is the cycloplegic effect last for several days after instillation of a single drop of atropine (MPEP §2112(IV)).
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 before the effective filing date of the claimed invention to produce an atropine sulfate ocular composition (eyedrop formulation) including a cationic polymer (chitosan), a non-ionic polymer (polyvinyl pyrrolidone), a pharmaceutical carrier (water), and an anionic polymer, as suggested by OSTROW, and further to make the compositions preservative-free as antimicrobial preservatives are known to cause potential side effects, which compositions are shown to be stable for at least 6-months when stored in LDPE bottles, as taught by Berton et al., and further to optimize the amount of polymer viscosity adjusting agents (carbomer, chitosan, polyvinyl pyrrolidone) in an ocular atropine eyedrop formulation.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention because it would have required no more than an ordinary level of skill to formulate a pharmaceutical composition for topical ocular administration such as an eyedrop formulation of atropine including known constituent ingredients for the same. Therefore, the invention as a whole would have been 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, especially in the absence of evidence to the contrary.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103.
Claims 5 and 7-8 are further rejected under 35 U.S.C. 103 as being unpatentable over OSTROW in view of Berton et al., as applied to claims 1, 4, 5, 7-10, 12, 14, 16- 18, 20, 28-31, 35 and 36 above, and further in view of HOSSEINI (US 2017/0007635 A1; published January, 2017).
Applicants Claims
Applicant claims the formulation includes an anionic polymer (carbomer/polycarbophil) is present an amount of 0.2% w/v to about 2.0% w/v (instant claims 5 & 7), the cationic polymer (chitosan) is present in an amount of about 0.01% w/v to about 2.0% w/v (instant claims 1 & 8).
Determination of the scope
and content of the prior art (MPEP 2141.01)
OSTROW teaches ophthalmic compositions including atropine sulfate, as discussed above and incorporated herein by reference.
Berton et al. teaches the stability of low-dose atropine in LDPE containers, as discussed above and incorporated herein by reference.
Ascertainment of the difference between
the prior art and the claims (MPEP 2141.02)
The difference between the rejected claims and the teachings of OSTROW/Berton et al. is that these references do not expressly teach the anionic polymer species polycarbophil or the specific amount of chitosan.
HOSSEINI teaches ocular treatment (title), “The methods include administering to an eye of a subject in need thereof a composition comprising at least two active agents in an ophthalmically acceptable vehicle that can provide a sustained release of the at least two active agents.” (abstract).
HOSSEINI teaches that: “Embodiments of the present disclosure include wherein the vehicle comprises an aqueous suspension having a first viscosity, said suspension comprising from about 0.1 % to about 6.5% by weight, based on the total weight of the suspension, of a polycarbophil […]” ([0010]; also see, [0028], [0057] & [0066]). Instant claims 5 & 7, anionic polymer species polycarbophil; overlapping amount – MPEP §2144.05(I)).
HOSSEINI further teaches that: “said polycarbophil having average particle size of not more than about 50 μm in equivalent spherical diameter, and a sufficient amount of chitosan to allow said polycarbophil to remain suspended, wherein upon contact with tear fluid, said vehicle gels to a second viscosity which is greater than the first viscosity.” ([0010], also see [0011]). And that: “In the ophthalmically acceptable vehicle of the present disclosure, chitosan or other second polymer is present in an amount ranging from between about 0.01 % to about 0.5% […].” ([0062])(instant claims 1 & 8; cationic polymer species chitosan; overlapping amount – MPEP §2144.05(I)).
HOSSEINI further teaches examples ocular formulations including polycarbophil (0.95%) and chitosan (0.025%)(p. 11, Table 4 – [0088] through [0090])(instant claims 7-8).
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 before the effective filing date of the claimed invention to produce an atropine sulfate ocular composition (eyedrop formulation) including a cationic polymer (chitosan), a non-ionic polymer (polyvinyl pyrrolidone), a pharmaceutical carrier (water), and an anionic polymer, as suggested by OSTROW, and further to make the compositions preservative-free as antimicrobial preservatives are known to cause potential side effects, as discussed above, and further, alterative to optimizing the amounts of the cationic and anionic polymers, to have selected an amount known in the art pertaining to ocular eyedrop formulations for polycarbophil and chitosan, as suggested by HOSSEINI.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention because it would have required no more than an ordinary level of skill to formulate a pharmaceutical composition for topical ocular administration such as an eyedrop formulation of atropine including known constituent ingredients for the same. Therefore, the invention as a whole would have been 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, especially in the absence of evidence to the contrary.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103.
Claim 9 is further rejected under 35 U.S.C. 103 as being unpatentable over OSTROW in view of Berton et al., as applied to claims 1, 4, 5, 7-10, 12, 14, 16- 18, 20, 28-31, 35 and 36 above, and further in view of ARUMUGHAM (WO 2020/047197 A1; published March, 2020).
Applicants Claims
Applicant claims a sterile pharmaceutical composition, as discussed above, including a non-ionic polymer (polyvinyl pyrrolidone) in an amount of about 0.1% w/v to about 2.0 % w/v (instant claims 1 & 9).
Determination of the scope
and content of the prior art (MPEP 2141.01)
and content of the prior art (MPEP 2141.01)
OSTROW teaches ophthalmic compositions including atropine sulfate, as discussed above and incorporated herein by reference.
Berton et al. teaches the stability of low-dose atropine in LDPE containers, as discussed above and incorporated herein by reference.
Ascertainment of the difference between
the prior art and the claims (MPEP 2141.02)
The difference between the rejected claims and the teachings of OSTROW/Berton et al. is that these references do not expressly teach the specific amount of polyvinyl pyrrolidone.
ARUMUGHAM teaches ophthalmic compositions (title), including eyedrop formulations ([0066]), and “povidone at about 0.6% by weight” (p. 27, line 3)(povidone is syn. w/polyvinyl pyrrolidone)(instant claim 9). ARUMUGHAM further teaches aqueous formulations including carboxymethylcellulose-Na (sodium carboxymethyl cellulose) in an amount ranging from 0.1% to 0.5% and suggest “Substitutes” include Povidone (p. 30, [0082], Table – Row 1)(instant claim 9).
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 before the effective filing date of the claimed invention to produce an atropine sulfate ocular composition (eyedrop formulation) including a cationic polymer (chitosan), a non-ionic polymer (polyvinyl pyrrolidone), a pharmaceutical carrier (water), and an anionic polymer, as suggested by OSTROW, and further to make the compositions preservative-free as antimicrobial preservatives are known to cause potential side effects, as discussed above, and further, alterative to optimizing the amounts of the non-ionic polymer, to have selected an amount known in the art pertaining to ocular eyedrop formulations for polyvinyl pyrrolidone (Povidone), as suggested by ARUMUGHAM.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention because it would have required no more than an ordinary level of skill to formulate a pharmaceutical composition for topical ocular administration such as an eyedrop formulation of atropine including known constituent ingredients for the same. Therefore, the invention as a whole would have been 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, especially in the absence of evidence to the contrary.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103.
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over OSTROW in view of Berton et al., as applied to claims 1, 4, 5, 7-10, 12, 14, 16- 18, 20, 28-31, 35 and 36 above, and further in view of HORN (WO 2016/205068 A1; published December, 2016 – Of Record as cited by Applicant on 11/18/2024).
Applicants Claims
Applicant claims a sterile pharmaceutical composition for contacting an ocular surface of a mammal, as discussed above, wherein the pharmaceutical composition has a viscosity of about 1 cP to about 20 cP (instant claim 19).
Determination of the scope
and content of the prior art (MPEP 2141.01)
OSTROW teaches ophthalmic compositions including atropine sulfate, as discussed above and incorporated herein by reference.
Berton et al. teaches the stability of low-dose atropine in LDPE containers, as discussed above and incorporated herein by reference.
Ascertainment of the difference between
the prior art and the claims (MPEP 2141.02)
The difference between the rejected claims and the teachings of OSTROW/Berton et al. is that these references do not expressly teach their ocular eyedrop formulations have a viscosity in the range of about 1 cP to about 20 cP (instant claim 19).
HORN teaches storage stable compositions for treating refractive errors of the eye (title, abstract, see whole document). HORN teaches that: “The viscosity of compositions of the present invention comprising a viscosity enhancer may be from about 1 to about 5,000 cps prior to topical instillation in the eye. As a result of the shear force applied to the composition as it exits the device used for administration the viscosity is lowered to a range from about 1 to about 50 cps upon topical instillation, preferably from about 15 to about 35 cps,” (p. 14, [0092])(instant claim 19, viscosity - overlapping amount – MPEP §2144.05(I)). HORN further teaches the inclusion of viscosity enhancers including chitosan carbomer, and polyvinyl pyrrolidone, among others. And teaches that: “In a preferred embodiment the viscosity enhancer will have an equilibration viscosity less than 100 cps, preferably from about 15 to about 35 cps, and most preferably at about 30 cps.” (p. 20, [0120]).
HORN teaches the inclusion of cycloplegic agents including atropine in amounts of about 0.01% to about 0.10% w/v (p.24, [0138]).
HORN teaches eyedrops (p. 37, [0226]; p. 38, [0238]).
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 before the effective filing date of the claimed invention to produce an atropine sulfate ocular composition (eyedrop formulation) including a cationic polymer (chitosan), a non-ionic polymer (polyvinyl pyrrolidone), a pharmaceutical carrier (water), and an anionic polymer, as suggested by OSTROW, and further to make the compositions preservative-free as antimicrobial preservatives are known to cause potential side effects, as discussed above, and further to adjust the ocular composition (eyedrop formulation) viscosity to a viscosity of about 1 cP to about 20 cP, as suggested by HORN for an ocular eyedrop formulation.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention because it would have required no more than an ordinary level of skill to formulate a pharmaceutical composition for topical ocular administration such as an eyedrop formulation of atropine including known constituent ingredients for the same. Therefore, the invention as a whole would have been 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, especially in the absence of evidence to the contrary.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103.
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 §§ 706.02(l)(1) - 706.02(l)(3) 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1, 4, 5, 7-10, 12, 14, 16-20, 28-31, 35 and 36 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 4, 6-13, 17-20, and 22 of copending Application No. 18/827,095 (hereafter ‘095) in view of HORN (WO 2016/205068 A1; published December, 2016).
The instant claims are discussed above.
Copending ‘095 claim 1 is identical to instant claim 1. Copending ‘095 claims 3, 4, 6-10, 11, 12, 13, and 35 are equivalent to instant claims 4, 5, 7-12, 14, 17, 18 and 22. Copending ‘095 claims 17-20 are substantially equivalent to instant claims 28-31. Copending ‘095 claims 22-23 are substantially equivalent to instant claims 35-36.
The difference between the instantly rejected claims and the claims of copending ‘095 is that the claims of copending ‘095 do not expressly claim (1) the inclusion of pH adjusting agents (instant claim 16); (2) a viscosity is in the range of about 1 cP to about 20 cP (instant claim 19), on the specific pH range of about 5.0 to abut 8.0 (instant claim 20)
HORN teaches storage stable compositions for treating refractive errors of the eye, as discussed above and incorporated herein by reference. HORN further teaches that: “For the present invention while pH range of 5.0 to 8.0 is tolerated, preferred embodiments are at pH 5.5 to 7.5 and more preferably 6.5 to 7.0.” (p. 22, lines 9-10). And, consistent with copending ‘095 claim 9, HORN teaches the inclusion of buffers to adjust the composition pH (p. 27 [0145]).
It would have been prima facie obvious before the effective filing date of the claimed invention that the instantly rejected claims are an obvious variant of the claims of copending ‘095 because most of the claims are identical or substantially identical, and the differences are clearly obvious in view of the teaching of the prior art reference HORN. The skilled artisan would have been motivated to modify the claims of copending ‘095 and produce the instantly rejected claim because atropine, chitosan, polyvinyl pyrrolidone, poloxamers, polycarbophil/carbomer, and water are each suggested for the compositions of ‘095, and it would therefore been prima facie obvious to select the same. Furthermore, the skilled artisan would have had a reasonable expectation of success in producing the invention of the instantly rejected claims because it would have required no more than an ordinary level of skill to formulate a pharmaceutical composition for topical ocular administration such as an eyedrop formulation of atropine including known constituent ingredients for the same.
This is a provisional obviousness-type double patenting rejection.
Double Patenting – Statutory
A rejection based on double patenting of the “same invention” type finds its support in the language of 35 U.S.C. 101 which states that “whoever invents or discovers any new and useful process... may obtain a patent therefor...” (Emphasis added). Thus, the term “same invention,” in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957).
A statutory type (35 U.S.C. 101) double patenting rejection can be overcome by canceling or amending the claims that are directed to the same invention so they are no longer coextensive in scope. The filing of a terminal disclaimer cannot overcome a double patenting rejection based upon 35 U.S.C. 101.
Claims 1, 4, 5, 7-10, 12, 14, 17, 18 and 35 are provisionally rejected under 35 U.S.C. 101 as claiming the same invention as that of claims 1, 3, 4, 6-9, 10, 11, 12, 13 and 22, respectively, of copending Application No. 18/827,095 (reference application). This is a provisional statutory double patenting rejection since the claims directed to the same invention have not in fact been patented. The claims are compared in the obvious-type double patenting rejection, as discussed above.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Zhu et al. (“The development of polycarbophil as a bioadhesive material in pharmacy,” 2013; ELSEVIER; Asian Journal of Pharmaceutical Sciences, Vol. 8, pp. 218-227) is cited as teaching the benefits of polycarbophil in ocular drug delivery systems (see whole document, particularly p. 221, §2.1). Austermann et al. (“Corneal Penetration of Low-Dose Atropine Eye Drops,” 2021, MDPI; Journal of Clinical Medicine, Vol. 10, No. 588, pp. 1-12) is cited as teaching low-dose atropine treatments (see whole document). Wang et al. (“The Penetration and distribution of topical atropine in animal ocular tissue,” 2019; John Wiley & Sons; Acta Ophthalmologica, Vol. 97, pp. e238-e247) is cited as teaching the ocular pharmacokinetics of atropine in an animal model (New Zealand white rabbits)(see whole document).
Conclusion
Claims 1, 4, 5, 7-10, 12, 14, 16-20, 28-31, 35 and 36 are pending and have been examined on the merits. The abstract of the disclosure is objected to. Claims 1, 4, 5, 7-10, 12, 14, 16-20, 28-31, 35 and 36 are rejected under 35 U.S.C. 112(b); claims 1, 4, 5, 7-10, 12, 14, 16-20, 28-31, 35 and 36 are rejected under 35 U.S.C. 103; claims 1, 4, 5, 7-10, 12, 14, 16-20, 28-31, 35 and 36 are provisionally rejected on the ground of nonstatutory double patenting; and claims 1, 4, 5, 7-10, 12, 14, 17, 18 and 35 are provisionally rejected under 35 U.S.C. 101 as claiming the same invention as (Statutory Double Patenting) that of claims 1, 3, 4, 6-9, 10, 11, 12, 13 and 22, respectively, of copending Application No. 18/827,095. No claims allowed at this time.
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/IVAN A GREENE/Examiner, Art Unit 1619
/TIGABU KASSA/Primary Examiner, Art Unit 1619
1 Hiraoka et al.; “Influences of Cycloplegia with Topical Atropine on Ocular Higher-Order Aberrations,” 2013, ELSEVIER, Ophthalmology, Vol. 120, Issue 1, pp. 8-13.
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