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 .
Telephone conversation:
Applicant noted that the limitations of the examined claims are found in withdrawn claims and therefore the finality of the previous action is improper. Further Applicant noted that the Application is track 1 case. Examiner argued that withdrawn claims are just that- withdrawn. As such anything in withdrawn claims are not considered and have no impact on interpretation of claims under examination. As such, normally a response to the office action needs to be placed on record.
However, Examiner agreed to withdraw the Final Rejection 05/06/2026 and file a new rejection.
Election/Restrictions
Applicant’s election without traverse of Group II claims 3-6, 9-12 and 15-18 in the reply filed on 01/13/2026 is acknowledged.
Upon further consideration claims 3-6, 9-12, 15-18 and 21-24 are examined together.
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.
Claim(s) 3-6, 9-12, 15-18 and 21-24 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wang US20170304306; Delwig,. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2679 (herein after Delwig2018); Delwig, Investigative Ophthalmology & Visual Science June 2020, Vol.61, 143 (herein after Delwig2020); and Baranowski, Scientific World Journal Volume 2014, Article ID 861904, 14 pages further in view of Horton, Master the Maze of Artificial Tears, Published November 20, 2018; Alviset, Pharmaceutics 2022, 14, 453, 1-17 and Dubald, Pharmaceutics 2018 Jan 13;10(1):10.
Wang teaches the active ingredient of the claims, at top of page 19 (see later in this action for more on the concentration, ingredient, formulation etc.). Wang at page 6, column B [0146], teaches that the active ingredient is selective inhibitor of NaV 1.7. Wang at page 47, column B [0484] teaches that the ingredient can be administered among other routes topically to eye. Wang at page 6,column B [0147] teaches that the NaV 1.7.inhibitor is useful for treatment of pain. Wang at page 1, column A, [003] [0003] teaches that voltage-gated ion channels play a critical role in the electrical activity of neuronal and muscle cells. NaV1.7 stands for voltage-gated sodium channel subtype 1.7. .Again, NaV 1.7 is a voltage-gated sodium channel, encoded by the SCN9A gene, that acts as a crucial "volume knob" for pain signals in peripheral sensory neurons. It regulates neuronal excitability and is essential for transmitting pain, making it a major target for non-addictive pain therapies. Mutations can cause severe pain disorders or complete pain insensitivity, see Wang at page column B [0494].
While Wang teaches the critical limitation of the active ingredient (of the independent claims 3, 9 and 15 more on specifics later) and its inherent property (underlying the biochemical mechanism) for the treatment of pain, [0484], for example associated with neuronal cels, Wang does not specifically teach the laundry list of eye conditions such as dry eye and related neuropathic pain disorders of the dependent claims 2-6, 10-12 and 14-18.
Further Wang does not teach the limitation of the combination of inactive components, polysorbate 80 (PS80, Hydroxypropyl-β- cyclodextrin (HPβCD) and phosphate buffer.
The teachings of Baranowski, Horton, Alviset, Dubald Delwig2018-2020 are invoked to cure the deficiency of Wang:
Delwig2018 and Delwig2020 explicitly teach NaV 1.7 inhibitors are useful as active ingredients for treating ocular disorders:
Delwig2018 tiled ‘Evaluation of Selective NaV1.7 Inhibitors for the Treatment of Ocular Pain’ concludes that compelling corneal exposure and ocular tolerability results obtained with a NaV 1.7 inhibitor support the development of NaV 1.7 inhibitor as a safe and effective topical ophthalmic analgesic. as a safe and effective topical ophthalmic analgesic. Delwig2018 teach that such a compound would find use in the treatment of acute and chronic ocular pain and discomfort associated with dry eye syndrome, corneal injuries, corneal infections, and post-operative pain following ocular surgical procedures (falling under the scope of limitations of dependent claims 2-6, 10-12 and 14-18).. Likewise, Delwig2020 tiled “NaV1.7 inhibitors relieve ocular discomfort in a rat model of dry eye disease” supportive of Delwig2018 conclusions that selective inhibition of NaV1.7 in the cornea relieves chronic ocular pain caused by dryness of the ocular surface.
While Delwig2018 and Delwig2020 independently teach the underlying mechanism of action of NaV1.7 inhibitors in the claimed method of treatment including for the specifically recited dry eye pain, Delwig2018 and Delwig2020 do not disclose the chemical structures of NaV1.7 inhibitors.
It is within the common knowledge of one in the art that pharmaceutical treatment relies on the inherent biochemical property of drugs (independent of the chemical structure of the drug). Here, the inherent property of the compound of Wang is linked inexorably to the treatment of ocular pain further in view of Delwig2018 and Delwig2020 which teach unequivocally that compounds with the said inherent property are useful as active ingredient in the claimed method. Simple substitution of one known (Wang) biochemically equivalent element for another (Delwig2018 and Delwig2020) to obtain predictable result is obvious.
Specifics of the formulation:
The examined method claim(s) 3, 9 15 and 21 depend on the limitations of the formulation of base claim(s) ((1 for) 3, (7 for 9), (13 for 15) and (19 for 21)). The said formulation(s) as limited (see more below), as per disclosure [004] at page 2 [0018] at page 4 provide for ‘high concentrations’ (that treat ocular irritation [0144] at page 28, treat dry eye [0159] at page 30 and pain [0167] (not the plethora of eye conditions listed in the dependent claims, more on this ‘not’ later).
Each and every limitations of the above formulation of claims 1,7, 13 and 19 are well known as result effective variables, in the ophthalmic drug dosage forms, as explicitly taught in the Review article of Baranowski titled
“Ophthalmic Drug Dosage Forms: Characterization and Research Methods”
(Note Review by definition is a comprehensive, critical synthesis of existing research on a specific topic, designed to summarize, analyze, and interpret the current state of knowledge, often highlighting trends, gaps, and future directions).
Using word search technique (see how below), disclosure in Baranowski with respect to optimization of these excipients (see formulation base claims 1, 7, 13 and 19)
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can be found.
How to Word search:
Use Control-F Search on iPhone or iPadCtrl+F (or Command on Mac) is a universal keyboard shortcut used to quickly find specific text, words, or phrases within documents, spreadsheets, or web pages. Pressing Ctrl+F opens a search box, usually in the top-right corner, allowing you to type in a term to instantly locate all its occurrences.
As ascertainable above, Baranowski teaching for recited
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at page 3, column A, is shown below:
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Likewise, Baranowski teaches component cellulose generically and specifically HPMC at page 3 column B and at page 4 column B. Similarly, Baranowski teaches phosphate buffer at page 9 column 9, emulsions at page 2 column A and so on.
Baranowski does not teach the instant amount w/w of NaV1.7 inhibitor or the excipients
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which provide the exemplified formulations at page 18-21, working examples 1-5.
But obviousness analysis, with respect to ‘about’ w/w of active ingredient, excipients(, pH): here is predicated on explicit Examination Guidelines summarized below:
It has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. The 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).
Again, the invention is a selective combination of the inventions by the prior arts done in a manner obvious to one of ordinary skill in the art. Patent for the combination of known elements wherein their functions remain the same withdraws “what is already known into field of its monopoly and diminishes resources available to skilled men”. Sakraida v. Ag Pro, Inc.189 USPQ 449, 425 US 273, (1976).
Specifics of the alleviated ocular conditions:
As to the laundry list of disease limitations of dependent claims
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s,
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The working examples in the disclosure do not teach any of the above, but limited as pointed above, to the
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s taught in the
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references cited here.
Motivation: Other than addressing medical needs of alleviating ocular pain, additional motivations include profit: See Ophthalmic Formulation Development: Inside Ophthalmic Preparation Ophthalmic Formulation Development: Inside Ophthalmic Preparation
July 28, 2022: Ophthalmic Formulation Development: Inside Ophthalmic Preparation
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With the above elaborated ‘Teaching Suggestion and Motivation’ taken together there is reasonable expectation of success for the claimed method as limited.
Baranowski Review article on ophthalmic Drug Dosage Forms: Characterisation and Research Methods, the all the recited components of the claims are known in the art. see column B page 1
One of the first modifications to conventional forms of ophthalmic drugs was introducing polymers to formulation, which enabled longer contact time of active ingredient and the corneal surface, thus increasing its bioavailability. Next possibility to modify the ophthalmic forms active ingredients ’bioavailability involved introducing excipients to formulation, which enhanced drugs’ penetration into the eyeball. These excipients included chelating agents, surfactants, and cyclodextrins, which, along with active ingredients, form inclusion complexes. This increases solubility, permeability, and bioavailability of poorly soluble drugs.
Baranowski further provides additional teachings on the individual inactive elements. Thus, for example, guidance on ‘buffer’ and ‘cyclodextrins’ is found at page 2, column A section under Topical Ophthalmic Drug Forms.
Again, hydroxypropyl-beta-cyclodextrin (HβCD), HPMC, polysorbate 80 and phosphate buffer, are frequently combined in ophthalmic formulations to solubilize lipophilic drugs, stabilize therapeutic proteins, and maintain physiological pH.
Applicant is encouraged to locate the specific limitations in the cited Review article using word search technique. Examples in the following further points out the what, the how and the why as well as motivation for the inactive ingredients/excipients in the claims:
According to Horton, although the prevalence and incidence of dry eye disease (DED) varies widely due to a lack of standardized testing and criteria, a recent report estimates more than 16 million adults in the United States are diagnosed with DED.1 Dry eye accounts for almost 25% of medical eye care visits and has been estimated to cost the US healthcare system $3.84 billion annually—this number increases to $55.4 billion when considering societal costs.
More specifically Horon teach that Polysorbate 80 is included in eye drops to aid in the emulsification of formulations.
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Just above this Table, Horton provides real-life examples:
Polysorbate 80 is included in eye drops to aid in the emulsification of formulations with oil, such as Soothe XP (Bausch + Lomb) and Refresh Optive Mega-3 (Allergan). The latter includes polysorbate 80, glycerin 1% and castor oil, all of which are inactive ingredients in Restasis (Allergan).
Reference to polysorbate 80 appears 56 times in Alviset teachings titled New Preservative-Free Formulation for the Enhanced Ocular Bioavailability of Prostaglandin Analogues in Glaucoma which includes including dry eye formulations.
Similarly, teachings with respect to buffer (pH) appears 20 times in Dubald.
Response to Remarks 04/24/2026:
Applicants arguments focus on the following:
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(emphasis by Examiner).
Applicants then expands on the above and assert that since
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are not present in the cited references, the rejection should be withdrawn:
Response:
Applicants arguments are not persuasive.
Firstly as to
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it is noted that the rejection is not under Claim Rejections - 35 USC § 102.
The active ingredient (Wang compound A or salt), its inherent biochemical property (Delwig) and the inactive ingredients, their inherent property for their routine applications in ophthalmic formulations (Baranowski, Horton, Alviset and Dubald) are taught in the art.
Obviousness can 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.
Although the prior art did not specifically disclose the amounts of each constituent, it would have been obvious to one of ordinary skill in the art at the time Applicants' invention was made to determine all operable and optimal concentrations of components because concentrations of the claimed components are art-recognized result effective variables because they have the ability for controlling parasites, which would have been routinely determined and optimized in the pharmaceutical art.
Examination guidelines with respect to combination of these and ranges is noted below:
It has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. The 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).
Accordingly, the claims do not recite an unobvious distinction over the prior art. Further, a reference is relevant not only for what it expressly teaches, but also for what it would have conveyed to one of ordinary skill in the art. See In re Opprecht, 12 USPQ2d 1235, 1236 (Fed. Cir. 1989); In re Bode, 193 USPQ 12 (CCPA 1976). In light of the foregoing discussion, the Examiner finds that the claimed subject matter as a whole would have been obvious to one of ordinary skill in the art at the time the invention was made, in view of the cited references and the knowledge generally available in the art. Accordingly, the claims are rejected under 35 U.S.C. § 103.
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.
Claim(s) 3-6, 9-12, 15-18 and 21-24 is/are rejected under 35 U.S.C. 103 as being unpatentable over Babich US 20160130239 and Ahuja, Topical Ocular Delivery of NSAIDs", The AAPS Journal, 2008, Vol. 10, No. 2, pp. 229-241.
Babich teaches a pharmaceutical ophthalmic formulation comprising an active ingredient and a pharmaceutically acceptable buffer, osmolality adjuster, viscosity adjuster, solubilizer, or carrier (para [0533] In another embodiment, provided herein are compositions comprising an effective amount of a Compound and a pharmaceutically acceptable carrier or vehicle; see also para [0531] The Compound can also be administered ... topically to the... eyes), wherein the active ingredient is Compound A (pg 27, Table 1, Compound 49), wherein the concentration of Compound A, or a pharmaceutically acceptable salt thereof, is about 1 mg/mL-200 mg/mL (para [0528] In another embodiment, provided herein are unit dosage formulations that comprise a Compound dosage that achieves a target plasma concentration of the Compound in a patient or an animal model. In a particular embodiment, provided herein are unit dosage formulations that achieves a plasma concentration of the Compound ranging from approximately 0.001 µg/mL to approximately 100 mg/mL).
Ahuja teaches an ophthalmic formulation (abstract, Aqueous ophthalmic solutions of NSAlDs have been made using sodium, potassium, tromethamine and lysine salts or complexing with cyclodextrins/solubilizer) wherein the buffer is phosphate buffer (pg 234, col 2, para 2, Partition experiments between oil and phosphate buffer (pH 7.4) showed increased partition of ketorolac into the aqueous phase from sesame oil drop which could account for the increased permeation). It would have been obvious to a person having ordinary skill in the art to combine Ahuja with Babich because Babich teaches an ophthalmic formulation (para [0533] In another embodiment, provided herein are compositions comprising an effective amount of a Compound and a pharmaceutically acceptable carrier or vehicle; see also para [0531] The Compound can also be administered... topically to the... eyes) and Ahuja teaches wherein a compound has increased permeation due to the presence of phosphate buffer (pg 234, col 2, para 2, Partition experiments between oil and phosphate buffer (pH 7.4) showed increased partition of ketorolac into the aqueous phase from sesame oil drop which could account for the increased permeation) which could be used to enhance permeation of the compound taught by Babich.
Babich also teaches hydroxypropyl methylcellulose (HPMC) (para [0523] Suitable formulations can be prepared by methods commonly employed using conventional, organic or inorganic additives, such as... a dispersing agent (e.g., hydroxypropyl methylcellulose)), but Babich doesn't teach wherein the formulation comprises about 12% (w/w) HP-beta-CD, about 4% (w/w) polysorbate 80, and about 3% (w/w) HPMC in 20 mM phosphate buffer. However, Ahuja teaches an ophthalmic formulation (abstract, Aqueous ophthalmic solutions of NSAlDs have been made using sodium, potassium, tromethamine and lysine salts or complexing with cyclodextrins/solubilizer) and Ahuja further teaches wherein hydroxypropyl-beta-cyclodextrin (HPβCD) increases solubility of compounds when pH is low (pg 233, col 2, para 2, Since reducing the pH also leads to precipitation, a number of approaches like use of solubilizer like polyoxyethylene-35-castor oil, and hydroxypropyl-beta-cyclodextrin (33) have been employed) and Ahuja further teaches wherein polysorbate 80 facilitates compatibility with common eye drop ingredients (pg 238, col 2, para 3, The incompatibility of NSAlD with benzalkonium chloride, a cationic preservative, commonly used in eye drops, is avoided using polysorbate 80, cyclodextrins or tromethamine), and Ahuja teaches wherein a compound has increased permeation due to the presence of phosphate buffer (pg 234, col 2, para 2, Partition experiments between oil and phosphate buffer (pH 7.4) showed increased partition of ketorolac into the aqueous phase from sesame oil drop which could account for the increased permeation). It would have been obvious to a person having ordinary skill in the art to formulate the composition having HP-beta-CD, polysorbate 80, and phosphate buffer, because the teachings of Ahuja suggest that the compounds with have increased solubility at low pH, higher compatibility with common eye drop ingredients, and increased permeation. It would have been further obvious to prepare the composition having 12% (w/w) HP-beta-CD, about 4% (w/w) polysorbate 80, and about 3% (w/w) HPMC in 20 mM phosphate buffer by routine experimentation in order to optimize the characteristics of the composition in the course of development and commercialization. It would also have been obvious to combine Ahuja with Babich because Babich teaches an ophthalmic formulation (para [0533] In another embodiment, provided herein are compositions comprising an effective amount of a Compound and a pharmaceutically acceptable carrier or vehicle; see also para [0531] The Compound can also be administered... topically to the... eyes) and Ahuja teaches ophthalmic formulations (abstract, Aqueous ophthalmic solutions of NSAIDs have been made using sodium, potassium, tromethamine and lysine salts or complexing with cyclodextrins/solubilizer) wherein different agents enhance the characteristics of the formulation, which could be used to enhance the formulation of Babich.
All the claimed elements (active and inactive ingredients), their inherent properties providing for their use in ophthalmic formulations are known the cited art. It has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. The 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).
Accordingly, the claims do not recite an unobvious distinction over the prior art. Further, a reference is relevant not only for what it expressly teaches, but also for what it would have conveyed to one of ordinary skill in the art. See In re Opprecht, 12 USPQ2d 1235, 1236 (Fed. Cir. 1989); In re Bode, 193 USPQ 12 (CCPA 1976). In light of the foregoing discussion, the Examiner finds that the claimed subject matter as a whole would have been obvious to one of ordinary skill in the art at the time the invention was made, in view of the cited references and the knowledge generally available in the art. Accordingly, the claims are rejected under 35 U.S.C. § 103.
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.
Claim(s) 3-6, 9-12, 15-18 and 21-24 is/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 independent claims are drawn to limitations of withdrawn claims. Importing limitations from withdrawn claims would be tantamount to importing limitations from specification. Withdrawn claims are just that- withdrawn.
Note that although the claims are interpreted in light of the specification,
limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Also see, In re Zletz, 13 USPQ2d 1320,1322. “An essential purpose of patent examination is to fashion claims that are precise, clear, correct and unambiguous.”
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NIZAL S CHANDRAKUMAR whose telephone number is (571)272-6202. The examiner can normally be reached M-F 8-5 EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Andrew Kosar can be reached at (571) 272-0913. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/NIZAL S CHANDRAKUMAR/Primary Examiner, Art Unit 1625
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