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 Claims/Application
The preliminary amendment dated 06/26/2024 is acknowledged. Claims 3 – 14, 16, and 18 – 22 are amended. Claims 1 - 25 are pending and are examined on the merits herein.
Priority
Applicant's claim for the benefit of a prior-filed application under 35 U.S.C. 119(e)
or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. The instant application,
filed on 11/10/2023, claims domestic benefit to U.S. provisional application no.
63/383,435, filed on 11/11/2022.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 5 and 21 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The term “high” in claim 5 is a relative term which renders the claim indefinite. The term “high” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Claim 5 can be modified by providing a range or a specific value as given in claims 6, and 7.
Claim 21 recites “the osmolality of the formulation ranges from 275 mOsm/kg”, which implies that 275 mOsm/kg is the lower limit for osmolality. However, it doesn’t provide an upper limit for the range. So, it is unclear whether the osmolality must be 275 mOsm/kg, or the applicant intended for a range.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 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.
Claims 1 – 4, 8 – 18, 20, and 22 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by EP 2263648 (Published on 12/22/2010, PTO-892).
EP’648 teaches an ophthalmic composition, in particular for stabilization of the lacrimal film, corneal cicatrization, restoration of the saline content of the tear, and osmoprotection, comprising an aqueous solution of cobalamine, sodium hyaluronate, and other substances that by acting synergistically are able to stabilize chemically cobalamine at a pH in the 6.0 – 7.5 range, ensuring an excellent ocular tolerability (pg. 1, col. 1, (57)).
EP’648 teaches a composition characterized by a particular combination of active principles (mainly: cobalamine, hyaluronic acid and/or its salts, and advantageously also taurine) and excipients (such as, for example: sorbitol, trisodium citrate, pH-stabilizing substances, etc.), which, by acting synergistically, are able to stabilize chemically (cyano)cobalamine at a pH within the range 6.0 to 7.5, preferably 7.0 to 7.4, ensuring an excellent ocular tolerability (pg. 2, [0008]). EP’648 teaches that the composition is preferably formulated with a Na+/K+ ratio of approximately 5.20, which, together with the slight hypotonia of approximately 240 mOsm/L, is able to normalize, in the cases of “dry-eye”, the levels of Na+ and K+ and the osmolarity at physiological values after just a few administrations (pg. 2, [0011], lines 46-48). EP’648 teaches that the formulation is chemically stable (pg. 3, [0017], line 12). EP’648 teaches various compositions in Examples 1 and 2 (pg. 3, [0017]), with an exemplified compositions prepared by varying the concentrations of the various components shown below (pg. 4, [0018]).
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Concentrations in %(weight/volume):
Sodium Hyaluronate:0.4%-0.6%; Cyanocobalamine:0.04%-0.06%; Taurine:0.4%-0.6%; Sorbitol:0.4%-0.6%; Trisodium citrate x 2 H2O:0.12%-0.16%; NaCl:0.3%-0.4%; KCl:0.08%-0.12%; MgCl2 x 6 H2O:0.02%-0.03%; Dibasic sodium phosphate dodecahydrate:0.1%-0.16%.
Regarding claims 1 – 4, 8, 9, 12, and 13, EP’648 teaches a composition comprising at least one natural humectant, sodium hyaluronate; at least one amino acid, taurine; and at least one vitamin, cyanocobalamine; and the formulation is free of preservatives, borate, and polyethylene glycol. Regarding claims 10 and 11, these claims depend from instant claim 9, and recite additional limitations of the at least one vitamin, vitamin C. However, claim 9 recites alternative limitations that the at least one vitamin is chosen from vitamin C and vitamin B12. Thus, the limitations of claims 10 and 11 are met by EP’648 teaching the presence of cyanocobalamine in the composition.
Regarding claims 14 – 18, 20, and 22, EP’648 teaches compositions further comprising of a natural electrolyte, NaCl, KCl, and MgCl2; and one natural buffer, trisodium citrate; wherein the pH of the formulation is in the range of 6.0 – 7.5, and the osmolality is in the range of 220 – 260 mOsm/L, and the formulation is chemically stable.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
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.
Claim 1, and 19 are rejected under 35 U.S.C. 103 as being unpatentable over EP 2263648 (Published on 12/22/2010, PTO-892).
The teachings of EP’648 are as discussed in the 102 rejection above.
The teachings of EP’648 differ from the instantly claimed invention in that it teaches the pH range 6.0 to 7.5 for the ophthalmic formulation, however not a specific ophthalmic formulation of pH 7.5.
It would have been prima facie obvious to adjust the pH of the ophthalmic formulation taught by EP’648 at 7.5 to arrive at the instantly claimed invention as EP’648 teaches the pH range 6.0 to 7.5 for the ophthalmic formulation.
In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). (MPEP § 2144.05(I)) Moreover, 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. “[W]here 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, 456, 105 USPQ 233, 235 (CCPA 1955). (MPEP § 2144.05(II)) “The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.” In re Peterson, 315 F.3d 1325, 1330, 65 USPQ2d 1379, 1382-83 (Fed. Cir. 2003).
Claims 5 – 7 are rejected under 35 U.S.C. 103 as being unpatentable over EP 2263648 (Published on 12/22/2010, PTO-892) as applied to claims 1 – 4, 8 – 20, and 22, further in view of WO 2018/158681 (PTO-892).
The teachings of EP’648 are stated above.
The teachings of EP’648 differ from the instantly claimed invention in that it is does not teach the molecular weight of sodium hyaluronate used in the ophthalmic composition.
WO’681 teaches an ophthalmic composition comprising cobalamin, taurine and at least one tear substitute for use in the regeneration of corneal nerve fibres in subjects who have undergone a keratoplasty operation (Abstract).
WO’681 teaches that the ophthalmic composition exhibits a physiologically acceptable pH, more preferably between 6.5 and 7.5 (pg. 6, lines 24,25), and the ophthalmic composition has a physiologically acceptable osmolarity, more preferably between 200 and 270 mOsm/kg, even more preferably between 220 and 260 mOsm/kg (pg. 6, lines 24 – 26). WO’681 teaches that the glycosaminoglycans which can be used are selected from the group consisting of: hyaluronic acid or a pharmaceutically acceptable salt thereof, more preferably sodium hyaluronate, chondroitin sulphate, and mixtures thereof, and said at least one glycosaminoglycan has a molecular weight ranging from 500 to 1200 kDa (pg. 7, lines 16 – 20), and advantageously, this molecular weight is more tolerable for the patient (pg. 7, line 22). WO’681 teaches that the composition comprises 0.03% - 0.07% by weight of cyanocobalamin, 0.3% - 0.7% by weight of taurine and 0.3% - 0.7% by weight of sodium hyaluronate. Advantageously, this specific combination of components and their presence in specific amounts allows obtaining optimal results in the regeneration of corneal nerve fibres (pg. 8, lines 5 – 7). WO’681 teaches that the buffering agents or acidity regulators help maintain the pH of ophthalmic products as close as possible to the physiological one, and this action is fundamental to allow good tolerability of the ophthalmic preparations and to preserve their efficacy, and provides an example of buffering agents inclusive of sodium hydroxide, sodium citrate, and sodium bicarbonate (pg. 8, line 17 – 23). WO’681 exemplifies in Example 1, a composition containing 0.4% sodium hyaluronate and salts such as potassium and magnesium for moistening and lubricating the ocular surface (pg. 9, lines 11 – 13), an ophthalmic aqueous solution containing 0.5% by weight of sodium hyaluronate, 0.5% by weight of taurine and 0.05% by weight of vitamin B12, having pH 7, osmolarity 240 mOsm/kg and molar ratio Na+/K+ 5.2 (pg. 9, lines 25 – 28).
Regarding claims 5 – 7, it would have been prima facie obvious to combine EP’648 with WO’681 before the effective filing date of the claimed invention for the composition to be prepared with high molecular weight sodium hyaluronate as WO’681 teaches that the glycosaminoglycan has a molecular weight ranging from 500 to 1200 kDa (pg. 7, lines 16 – 20), to arrive at an ophthalmic formulation of the instantly claimed hydration formulation. One of ordinary skill in the art would have been motivated to use a high molecular weight sodium hyaluronate in the range 500 to 1200 kDa, or more specifically sodium hyaluronate of molecular weight 800 kDa with a reasonable expectation of success because WO’681 teaches that advantageously, this molecular weight, 500 to 1200 kDa, is more tolerable for the patient (pg. 7, line 22).
Claim 21 is rejected under 35 U.S.C. 103 as being unpatentable over EP 2263648 (Published on 12/22/2010, PTO-892) as applied to claims 1 – 4, 8 – 20, and 22 above, and further in view of CN 107913246 (Published on 04/17/2018, PTO-892).
The teachings of EP’648 were as discussed above.
The teachings of EP’648 differ from the instantly claimed invention in that EP’648 does not teach the osmolality of the formulation ranges from 275 mOsm/kg.
CN’246 teaches an application of etimicin and pharmacologically acceptable salt or inclusion compounds thereof in preparation of a local eye medicine or medicine composition for preventing or treating eye diseases, xerophthalmia or dry eye syndromes, caused by conjunctivitis, angular blepharitis, keratitis, scleritis, trachoma and sensitive bacterium infection, of people or mammals. Eye preparations comprise eye drops, eye gel and the like. The medicine has better safety and effectiveness in a certain range (Abstract).
CN’246 teaches that the pharmaceutically acceptable carriers or absorption enhancers or humectants and the like may comprise: water, chiral or racemic or D- or L- or racemic amino acids or salts thereof such as D- or L- or DL-L Lysine, lysine acetate, cysteine, methionine, arginine or arginine acetate, or aspartic acid or sodium aspartate, glutamic acid, glycine, taurine, alanine, Valine, leucine, isoleucine, serine, threonine, cysteine, cystine, methionine, asparagine, glutamine, 5-hydroxylysine, histidine , phenylalanine, tyrosine, tryptophan, 3-hydroxyproline, 4-hydroxyproline, valine, homocysteine, homocysteine, homoserine, ornithine, Citrulline, creatine, 3-alanine, theanine, 2-aminobutyric acid, 4-aminobutyric acid, 2-amino-2-methylpropionic acid, 2-methyl-3-aminopropionic acid , 2,6-diaminopimelic acid, 2-amino-3-phenylbutyric acid, phenylglycine, canavanine, paraconidine, 4-hydroxyarginine, 4-hydroxyornithine , High arginine, 4-Hydroxyhomo-L-Arginine, β-Lysine, 2,4-Diaminobutyric acid, 2 3-diaminopropionic acid, 2-methylserine and the like, or a unit or polycarboxylic acid or a pharmaceutically acceptable salt thereof, gallic acid, propyl gallate, ethyl gallate, gallic acid esters, malic acid, succinic acid, ascorbic acid , L-ascorbic acid, sodium ascorbate, isoascorbic acid, sodium erythorbate, niacin, nicotinamide, pantothenic acid, sodium pantothenate, calcium pantothenate, vitamin B1, vitamin B2, vitamin E, beta-carotene, pyridoamine hydrochloride, glutathione Glycine, allantoin, citric acid, or sodium citrate, or lactic acid, sodium lactate, lactobionic acid, sodium lactobionate, gluconic acid, sodium gluconate, or trehalose, urea, thiourea, or maltitol, sorbitol, One or more of mannitol, lactitol, xylitol, erythritol, hyaluronic acid or sodium hyaluronate or a hydrate thereof or a pharmaceutically acceptable salt thereof or an isomer thereof, and the like, sorbitol Including one or more of D-sorbitol, anhydrous sorbitol or sorbitol hemihydrate or sorbitan monohydrate or instant sorbitol and the like, all of which include isomers thereof; usually, these compounds are used The concentration range can be 0.000 to 5.0%. The above-described wetting agents and the like are helpful in the composition to reduce local adverse reactions of drugs (pg. 5, para. 9).
CN’246 teaches that the composition comprises of hyaluronic acid or sodium hyaluronate, but is not limited to, macromolecular hyaluronic acid (molecular weight range 1,800,000-2,200,000), middle molecular hyaluronic acid (molecular weight range 1,000,000-1,800,000), small molecule hyaluronic acid (molecular weight range 200,000- 1,000,000), medium and small molecule hyaluronic acid are more preferred (pg. 7, para. 1). CN’246 teaches many compounds inclusive of calcium chloride, and glycerol as a pharmaceutically acceptable isotonicity modifier in the pharmaceutical composition (pg. 7, para. 4). CN’246 teaches in the prescription of the eye gel, the concentrations of various components as the gel matrix is usually 0.5 ~ 100.0g, more preferably 1 ~ 60.0g, more preferably 1 ~ 20.0g; Stabilizer (antioxidant or stabilizer) is usually 0.05 ~ 200g, more preferably 1 ~ 150g, more preferably 1 ~ 120g; Antiseptic or bacteriostatic agent is usually 0.005 ~ 20g, more preferably 0.01 ~ 2g; Osmotic pressure regulator is usually 0.1 ~ 80.0g, more preferably 1 ~ 60.0g, more preferably 1 ~ 40.0g; The pH adjuster is usually 0.1 to 20.0 g, more preferably 1 to 20.0 g, more preferably 1 to 10.0 g; And, make up to 1000ml or 1000g with water (pg. 8, para. 5 – 12). CN’246 teaches a step in the eye drops preparation method that the pH value of the solution is adjusted to be between 5.8-7.8 (more preferred pH is between 6.0-7.5) (pg. 8, para. 13),
CN’246 exemplifies in Example 12, the Preparation of Etimicin Single Dose Packaging Eye Drops comprising of etimicin sulfate (calculated as etimicin) 1.0g, trehalose 3g, boric acid 0.8g, borax 6.2g, taurine 5g, vitamin C 2g, disodium edetate 0.2g, 2M citric acid The appropriate amount of solution and sodium citrate solution, proper amount of water for injection, and a suitable amount of 0.85% sodium chloride solution were adjusted to 1000 ml (pg. 16, para. 3,4). CN’246 teaches in Example 10 eye drops comprising of L-arginine (pg. 15, para. 7). CN’246 teaches the preparation of various ophthalmic compositions in Examples 1 – 18, with pH ranging from 6.2 – 7.0, and osmolality ranging from 290 – 310 mOsm/kg.
It would have been prima facie obvious to combine EP’648 with CN’246 before the effective filing date of the instantly claimed invention for the composition to have an osmolality ranging from 275 mOsm/kg as taught in the examples of CN’246 to arrive at the hydration formulation of the instantly claimed invention. One of ordinary skill in the art would have been motivated to prepare ophthalmic formulations with the desired osmolality and have a reasonable expectation of success because CN’246 teaches the preparation of several example compositions in the osmolality ranging from 290 – 310 mOsm/kg.
Claims 23 – 25 are rejected under 35 U.S.C. 103 as being unpatentable over EP 2263648 (Published on 12/22/2010, PTO-892) as applied to claims 1 – 4, 8 – 20, and 22 above, and further in view of WO 2018/158681 (PTO-892), and CN 107913246 (Published on 04/17/2018, PTO-892).
The teachings of EP’648 were as discussed above.
The teachings of EP’648 differ from the instantly claimed invention in that EP’648 does not teach all the components of the formulation, and their concentrations recited in the instant claims 23 – 25.
The teachings of WO’681, and CN’246 are as discussed above.
Regarding claims 23 – 25, as EP’648 disclosed the effective ophthalmic formulation comprising of sodium hyaluronate, sodium chloride, potassium chloride, sodium citrate, taurine, magnesium chloride, and cyanocobalamin, it would have been prima facie obvious to combine EP’648, with WO’681 and CN’246 before the effective filing date of the instantly claimed invention for the composition to include sodium bicarbonate, and sodium hydroxide as taught by WO’681, and glycerin, trehalose, vitamin C, arginine, leucine, and calcium chloride as taught by CN’246 to arrive at the hydration formulation of the instantly claimed invention. As EP’648 teaches formulation with Sodium Hyaluronate: 0.4%-0.6%; Cyanocobalamine: 0.04%-0.06%; Taurine: 0.4%-0.6%; Sorbitol: 0.4%-0.6%; Trisodium citrate x 2 H2O: 0.12%-0.16%; NaCl: 0.3%-0.4%; KCl: 0.08%-0.12%; MgCl2 x 6 H2O: 0.02%-0.03%; Dibasic sodium phosphate dodecahydrate: 0.1%-0.16%; and WO’681 teaches that the composition comprises 0.03% - 0.07% by weight of cyanocobalamin, 0.3% - 0.7% by weight of taurine and 0.3% - 0.7% by weight of sodium hyaluronate; and CN’246 teaches that the concentration of trehalose as 0.3% and Vitamin C as 0.2% (in Example 12), the concentrations of glycerin and calcium chloride as 0.1% - 1% (pH adjuster concentration in the eye gel preparation), and the concentration of Arginine and Leucine would be similar to Vitamin C as they are taught in the same category, it would have been prima facie obvious to optimize the concentrations of all the components of the ophthalmic formulation before the effective filing date of the instantly claimed invention to arrive at the hydration formulation of the instantly claimed invention. MPEP 2144.05 states:
"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. "[W]here 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, 456, 105 USPQ
233, 235 (CCPA 1955)."
It further would have been obvious to one of ordinary skill in the art at the time
the invention was made to optimize the amount of each component. One would have
been motivated to do so in order to arrive at an ophthalmic composition with the most beneficial effects to the subject. One of ordinary skill in the art would have a reasonable expectation of success since the prior art teaches a range that could guide the experimentation for the instantly claimed range of the various components of the formulation. It is noted that MPEP 2144.05 states: "In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990); In re Geisler, 116 F.3d 1465, 1469-71, 43 USPQ2d 1362, 1365-66 (Fed. Cir. 1997).
Conclusion
Claims 1 – 25 are rejected. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JANAKI ANANTH MAHADEVAN whose telephone number is (571)272-0230. The examiner can normally be reached Monday-Friday 8-5PM.
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/JANAKI ANANTH MAHADEVAN/Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner
Art Unit 1693
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