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 .
Current Status of 18/857,856
This Office Action is responsive to the amended claims of 10/18/2024.
New claims 21-40 have been examined on the merits.
Priority
This application is a national stage entry of PCT/EP2023/060256. This application also claims foreign priority to EP22305608.6 and EP22305577.3.
The instant claims find support from EP22305577.3. Therefore, the effective filing date is 04/20/2022.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 10/18/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Objection to Title
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed. See MPEP 606.
The following title is suggested: “Formulation of atropine”.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 21, 24-26, 27-28, 30-31, and 36 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by OSTROW (US 2020/297713A1; cited in the IDS of 10/18/2024).
OSTROW anticipates an ophthalmic gel (i.e. a composition in the form of a gel of claim 21; also see paragraph [0096]) comprising atropine (ref claim 1) and containing a Viscosity enhancing agent (i.e. thickening agent such as hydroxyethyl cellulose; Ref claim 10), and a buffer (such as citrate buffering agent; Ref claim 5). Also see example from table 7 (which has poloxamer, a mucoadhesive thickening agent, and sodium acetate, a buffering agent, at a pH 4.2).
There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference. Chemical properties are inherent to their compounds. See MPEP 2112 (II). Products of identical chemical composition can not have mutually exclusive properties. A chemical composition containing citrate buffer, and its properties, stabilizing the pH between 3.5 and 4.5, are inseparable. See MPEP 2112.01 (II).
This anticipates claims 21, 24-26.
OSTROW anticipates an additional agent of a preservative (paragraph [0019]). This anticipates claim 30.
OSTROW anticipates an additional agent capable of improving muco-adhesion of the composition (sodium alginate; paragraph [0175]). This anticipates claims 27-28 and 31.
OSTROW anticipates a kit including a suitable container like a syringe (paragraph [0345[). OSTROW anticipates a syringe dose dropper adapted for a viscous formulation (see paragraph [0359]. Examiner understands that the solution was transferred in a drop wise fashion through the dropper as a viscous formulation). This anticipates claim 36.
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.
Claim(s) 21-28, 30-33, 35-36, and 40 are rejected under 35 U.S.C. 103 as being unpatentable over OSTROW (US 2020/297713A1) and in view of Michelon (Michelon et al., “Atropine-induced toxicity after off-label sublingual administration of eyedrop for sialorrhoea treatment in neurological disabled patients”, BJCP, February 1, 2021) in view of DUBASHYNSKAYA (Dubashynskaya et al., “Polysaccharides in Ocular Drug Delivery”, Pharmaceutics, December 24, 2019)
OSTROW teaches claims 21, 24-26, 27-28, 30-31, and 36 above.
OSTROW teaches an ophthalmic gel (i.e. a composition in the form of a gel of claim 21; also see paragraph [0096]) comprising atropine (ref claim 1) and containing a Viscosity enhancing agent (i.e. thickening agent such as hydroxyethyl cellulose; Ref claim 10), and a buffer (such as citrate buffering agent; Ref claim 5). Also see example from table 7 (which has poloxamer, a mucoadhesive thickening agent, and sodium acetate, a buffering agent, at a pH 4.2).
There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference. Chemical properties are inherent to their compounds. See MPEP 2112 (II). Products of identical chemical composition can not have mutually exclusive properties. A chemical composition containing citrate buffer, and its properties, stabilizing the pH between 3.5 and 4.5, are inseparable. See MPEP 2112.01 (II).
OSTROW teaches using atropine or a salt thereof (ref claim 1). The artisan would have been motivated and expected to use either atropine or the salt thereof. This teaches claim 21.
OSTROW does not teach treating Sialorrhea, oral administration, or weight% of components of the composition.
MICHELON teaches that Sialorrhea is a troublesome and disabling symptom defined by the unintentional loss of saliva from the mouth, usually associated with swallowing disorders (abstract). MICHELON teaches off-label use of ophthalmic atropine eyedrop administered sublingually can be useful in treating sialorrhea (abstract).
The artisan would expect that OSTROW’s composition containing atropine to be effective in treating Sialorrhea because MICHELON’s composition containing the active ingredient atropine was useful in treating sialorrhea (abstract). This teaches claim 40. This also teaches the oral administration of claim 23.
MICHELON teaches a dosage of atropine eyedrops 1% single dose of 0.5 mg to 1 mg (page 3365 and Case 1). This helps teach the dosage in claims 35 and 37.
MICHELON also teaches that use of marketed atropine eyedrops 1% single dose of 0.4 mL seems the most convenient dosage form but it can lead to potential mishaps resulting in an increased risk of adverse effects (page 3365). This would help teach a motivation to decrease the amount of atropine % in the solution, thus helping teach claims 22 and 33.
OSTROW teaches 0.01 mg/g to 0.5 mg/g of atropine (ref claim 1), which is 0.001% (w/w) to 0.05%(w/w) of atropine.
DUBASHYNSKAYA teaches that hydroxyethyl cellulose and sodium alginate are known to be mucoadhesive and are known to be added to solutions (page 3 and 5). DUBASHYNSKAYA teaches that hydroxyethyl cellulose ranges between 0.25-1.6% (table 1) and could be up to 10% (page 5). Sodium alginate is taught with a max potency of 1 mg (DUBASHYNSKAYA table 1).
The artisan would have been motivated to optimize the dosage of atropine, hydroxyethyl cellulose, and sodium alginate, while making an oral administration solution and in order to avoid adverse reactions. MICHELON teaches a 1% of atropine and OSTROW teaches a lower dosage percentage. The artisan would have been expected to optimize from the range of 1% to 0.001 (w/w) %. DUBASHYNSKAYA teaches a range of hydroxyethyl cellulose between 0.25 and up to 10% (page 5 and table 1). DUBASHYNSKAYA also teaches sodium alginate has a max potency of 1 mg (table 1). 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. See MPEP 2144.05(II)A. Examiner has reviewed the instant specification and claims and has not found evidence that the dosage is critical. This teaches claims 22, 32 and 33.
The artisan would have been motivated to use single unit dose in order to avoid potential mishaps resulting in an increased risk of adverse effects (MICHELON page 3365), such as administering too much volume of the atropine solution. This teaches claims 35 and 37.
Claim(s) 21, 24-26, 27-28, 30-31, 36 and 38 are rejected under 35 U.S.C. 103 as being unpatentable over OSTROW (US 2020/297713A1) and in view of Michelon (Michelon et al., “Atropine-induced toxicity after off-label sublingual administration of eyedrop for sialorrhoea treatment in neurological disabled patients”, BJCP, February 1, 2021) and in view of KENT (Christopher Kent, “Preserving without Preservatives”, Review of Ophthalmology, February 20, 2006).
OSTROW teaches claims 21, 24-26, 27-28, 30-31, and 36 above.
MICHELON teaches “dropper systems” which examiner understands as a containing multiple-doses (page 3367).
KENT teaches a new eye drop dispenser design (i.e. an Airless Antibacterial Dispensing System; on page 3) eliminates the need to add chemicals to prevent product deterioration (page 1). KENT teaches that the new bottle design is the first preservative-free artificial tears formula to be available in a multi-dose bottle (page 1).
An artisan would have been motivated to use KENT’s multi-dose bottle given the advantages such as being antibacterial. The artisan would have expected to use KENT’s eyedrop bottle instead of MICHELON’s or OSTORW’s eyedroppers due to the advantages. This teaches claim 38.
Claim(s) 21, 24-26, 27-28, 30-31, 36 and 39 are rejected under 35 U.S.C. 103 as being unpatentable over OSTROW (US 2020/297713A1) and in view of Michelon (Michelon et al., “Atropine-induced toxicity after off-label sublingual administration of eyedrop for sialorrhoea treatment in neurological disabled patients”, BJCP, February 1, 2021).
OSTROW teaches a method of preparing a composition of claim 21 (example 2 paragraphs [0350-0353]). This helps teach claim 39.
The artisan would be expected and find it obvious to first make atropine solution (OSTROW example 2) before adding the rest of the ingredients. The artisan would also find it obvious to mix the rest of the ingredients to the atropine solution. This teaches claim 39.
Claim(s) 21, 24-26, 27-29, 30-31, and 36 are rejected under 35 U.S.C. 103 as being unpatentable over OSTROW (US 2020/297713A1) and in view of Michelon (Michelon et al., “Atropine-induced toxicity after off-label sublingual administration of eyedrop for sialorrhoea treatment in neurological disabled patients”, BJCP, February 1, 2021) in view of GIULIANO (Giuliano et al., “Mucosal Applications of Poloxamer 407-based Hydrogels: An Overview”, Pharmaceutics, September 12, 2018)
GIULIANO teaches Poloxamer (of claims 27- 29) 407 is a water-soluble, non-ionic triblock copolymer, which is liquid at room temperature, and become a gel when administered at body temperature (abstract). GIULIANO teaches Poloxamer is an attractive candidate as a pharmaceutical drug carrier (abstract).
GIULIANO teaches Sodium alginate exhibited the greatest degree of mucoadhesion (table 1). This helps teach claim 31.
The artisan would have been motivated to add a poloxamer in order to increase muco-adhesion, especially for a patient who has difficulty keeping liquids in their mouth (i.e. excessive drooling; MICHELON’s abstract). The artisan would expect that by adding a poloxamer to an atropine solution (from OSTROW) that it would be an effective pharmaceutical drug carrier. The artisan would have also been motivated to use sodium alginate, as it is known to be used for the same purpose. This teaches claims 27-29 and 31.
Conclusion
No claims are allowed as written.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GILLIAN A HUTTER whose telephone number is (571)272-6323. The examiner can normally be reached M-F 7:30-5.
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/G.A.H./Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625
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