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 .
Election/Restrictions
Applicant’s election without traverse of group I and species of betamethasone sodium phosphate as the corticosteroid and mycophenolic acid as the immunosuppressant in the first composition and betamethasone sodium phosphate in the second composition in the reply filed on October 30, 2025 is acknowledged.
The requirement is still deemed proper and is therefore made FINAL.
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. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 365(c) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 18/100,505, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. The use two compositions of different corticosteroid as claimed that are then used to treat dry eye in the absence and presence of an episodic flare up are not disclosed in this application so the conditions for benefit to US’505 are not met as this application fails to provide adequate support for the claims as currently presented.
Application Nos. 63/088,850 and PCT/US2021/052552 provide support for all but claim 11 which requires continued administration of the composition having the lower corticosteroid concentration after substantial alleviation of the flare up over the treatment period or until another flare up occurs. The subject matter of claim 11 is only disclosed in the instant application.
The instant application is correctly filed as a continuation-in-part application and the effective filing dates of the claims under examination are as follows:
The effective filing date of claims 10 and 12 – 20 is October 7, 2020.
The effective filing date of claim 11 is April 6, 2023.
Claim Objections
Claim 20 is objected to because of the following informalities: there is a period in line 1 of the claim and each claim should only contain one period at the end of the claim. Appropriate correction is required.
Claim Rejections - 35 USC § 112 – Indefiniteness
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 10 – 20 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. Step c) of claim 10 requires administration of the second composition “to substantially alleviate the episodic flare up”. The similar phrase “after the episodic flare up is substantially alleviated’ is present in claim 11. Neither the claims nor the specification definition the level of relief or alleviation required to “substantially alleviate” the episodic flare up. This wording indicates that a complete return to the ‘baseline’ need not be achieved in order to achieve substantial alleviation of the flare up but how much alleviation must occur and/or how close the treatment with the second composition must come to achieving what was the baseline cannot be determined. Therefore one of ordinary skill in the art cannot determine when to cease topically administering the secondary composition and as in claim 11, resume administration of the first composition for an additional period of time.
The dependent claims fall therewith.
Please clarify.
Claims 19 and 20 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. These claims require a “pharmaceutical-free” lubricant formulation with claim 20 reciting numerous ingredients with amounts and uses the open language of “comprising”, allowing the presence of additional, unrecited ingredients. The phrase “pharmaceutical-free” is defined at ¶ [0032] of the PGPub of the instant application but this definition does not sufficiently define the metes and bounds of the claims. The compounds that are subject to regulation as a drug, medicine or a controlled substance by the United States Food and Drug Administration (FDA) or foreign equivalent that are excluded from the scope of the formulation can change over time. That could result in the same formulation being within the scope of the claims at one point in time but no longer within the scope of the claims as the regulatory status of ingredients change or vice versa. Without clear, fixed boundaries that define the metes and bounds of the ingredients that are permitted or excluded from the claims, the scope of the pharmaceutical-free formulations of claims 19 and 20 cannot be determined. Please clarify.
Claim 20 is 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.
Amongst the ingredients recited in the lubricant formulation of claim 20 are sodium phosphate dibasic anhydrous, sodium phosphate monobasic anhydrous and water. As all the ingredients dissolve in water at pH 7.2, those compounds cannot be present in the anhydrous form in the composition. Given the aqueous nature of the composition, the sodium thiosulfate could be present as the pentahydrate form and the edetate disodium in the dihydrate form, although again upon dissolution of these materials to form the composition, all of the material is not present in the pentahydrate or dihydrate form respectively. Or should the claim be interpreted as a product-by-process claim in which the ingredients recited are in the preparation of the claimed lubricant formulation but the formulation itself does not necessarily comprise those ingredients in the final form? Please clarify.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 10, 11 and 13 – 19 are rejected under 35 U.S.C. 103 as being unpatentable over Karolchyl et al. (US 2017/0112936) in view of Brady et al. (WO 2017/196881) and Lienert et al. (Ophthalmology, 2016).
Karolchyl et al. discloses compositions that are a sterile gel with a therapeutically effective quantity of an active component and the use of such compositions for ophthalmic applications (whole document, e.g., abstract). The composition can be for treating dry eye syndrome (¶ [0007]). Various active components including at least one immunosuppressant and at least one corticosteroid can be present in the composition (¶¶ [0008] and [0054] – [0070]). One having ordinary skill in the art will determine, taking into account medical, pharmaceutical and other requirements and limitations, which active components are to be used dependent the disease, disorder or pathology being treated (¶ [0071]). The corticosteroid can be betamethasone with concentrations in the range of about 0.01 mg/mL to about 50.0 mg/mL disclosed in ¶ [0079]. Immunosuppressants suitable for treating dry eye syndrome include mycophenolic acid with concentrations in the range of about 0.01 mg/mL to about 50.0 mg/mL disclosed in ¶ [0078]. Mycophenolic acid is also disclosed as medicament for dry eye syndrome treatment in ¶ [0088]. Those having ordinary skill in the art can determine the optimal concentration for each specific active components based on medical, pharmaceutical and other considerations that are commonly taken into account (¶ [0089]). Kits including sealed sterile containers are disclosed (¶ [0118]).
An explicit description of criteria to determine optimal concentrations of the active agents such as the corticosteroid is not given.
Brady et al. discloses compositions for treating ocular inflammatory disorders such as dry eye (¶¶ [0006] and [0008]). Determining the therapeutically effective dose can take into account, among others, whether the treatment is for an active disease or disorder or the use is for prophylactic treatment, the nature of the ocular inflammatory disorder, severity of the condition, the stage of the disease or disorder, the route of administration (e.g., systemic versus localized delivery), the subject, depending on the species, age, body weight, general health, sex, diet, time of administration, and drug interaction (¶ [0108]).
Lienert et al. discloses that treatments for dry eye disease (DED) include artificial tears and topical steroids, although even with therapy, DED tends to persist (¶ bridging cols 1 and 2 on p 425). As shown in Figures 1 – 3, depending on the marker being measured, at least some patients indicated that symptoms such as ocular surface discomfort got worse even for those receiving treatment (Figure 2). The majority reported little or no change in ocular surface symptoms, vision-related symptoms, or the social impact of DED since diagnosis, and a similar number reported an improvement as reported worsening (¶ bridging p 427 and 428).
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to provide compositions as disclosed by Karolchyl et al. that comprise at least a corticosteroid and an immunosuppressant for the treatment of dry eye and a separate composition with a higher concentration of corticosteroid for use when symptoms of dry eye are worse, such as during an episodic flare up. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because the severity of the condition being treated and stage of the disease are factors when determining a therapeutically effective dose. Generally with more severe symptoms, a higher dose of the therapeutically active agent would be administered. As explicitly disclosed by Karolchyl et al., one of ordinary skill in the art can select the active components and optimal concentrations of those ingredients in the compositions that can be used to treat dry eye. The amount of a specific ingredient in a composition is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of ordinary skill to determine the optimal amount of each ingredient to add in order to best achieve the desired results based on factors such as the symptom severity and there is no evidence of record as to the criticality of the claimed compositions. The stage and/or severity of a condition can change over time, at least in some patients as discussed by Lienert et al., rendering obvious the use of a lower dosage of the therapeutically active ingredient if symptoms are steady or improve over time as generally, the lowest dose that provides the desired therapeutic effects are given to minimize the potential for side effects that would generally increase at higher doses. However, a worsening of symptoms can result in the need for a higher dosage of the corticosteroid at least until the symptoms improve, when the composition containing the lower dose can be used again.
As to claim 19, the artificial tears of Lienert et al. are taught as treatment for dry eye and there is no evidence of record that materials that such artificial tears are not pharmaceutical-free as required by this claim. “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) MPEP 2144.06. The use of artificial tears would replace natural tears while compositions such as those disclosed by Karolchyl et al. would exert a therapeutic effect on the underlying condition that mere replacement of natural tears with artificial tears does not.
Claim(s) 12 is rejected under 35 U.S.C. 103 as being unpatentable over Karolchyl et al., Brady et al. and Lienert et al. as applied to claims 10, 11 and 13 – 18 above, and further in view of Musunuri et al. (US 2018/0333414).
Karolchyl et al., Brady et al. and Lienert et al. are discussed above.
The use of a plurality of unit dose containers comprising the compositions with different concentrations a corticosteroid such as betamethasone is not disclosed.
Musunuri et al. discloses compositions comprising two or more of the active pharmaceutically ingredients recited in the abstract and using such compositions to treat an eye disorder such as dry eye syndrome (whole document, e.g., abstract). The formulations can be packaged in various package forms that are known in the field of topical ophthalmics such as sterile, preservative-free single-use packs or vials so the composition is sterilized and contained with the single-dose container (¶ [0064]). Multiple vials, such as 30 or 60 vials, can be packaged in a tray which can be dispensed intact with one vial or pack used each time and then discarded after use (¶ [0064]).
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to prepare a kit comprising a number of single-use vials of compositions containing different concentration of the therapeutic agent(s) that are provided for use to treat dry eye in a subject. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because kits comprising multiple sterile, single-use vials are a known package form for topical ophthalmics. As the tray can be provided as a whole, one of ordinary skill in the art would vary the number of vials of the different formulations based on the expected usage of a patient. The ongoing treatment in the absence of more severe symptoms could be the composition applied most often so more vials of that composition would be provided with a lower number of the composition with a higher concentration of therapeutic agent for when the patient experiences more severe symptoms.
Claim(s) 14 is rejected under 35 U.S.C. 103 as being unpatentable over Karolchyl et al., Brady et al. and Lienert et al. as applied to claims 10, 11 and 13 – 18 above, and further in view of Koverech et al. (WO 2012/084446).
Karolchyl et al., Brady et al. and Lienert et al. are discussed above.
The elected salt of betamethasone, betamethasone sodium phosphate, is not specifically disclosed.
Koverech et al. discloses salts or derivatives of betamethasone include betamethasone sodium phosphate (p 3, ¶ 3).
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to use a salt such as betamethasone sodium phosphate in the formulations disclosed by Karolchyl et al. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because salts of pharmaceutically acceptable ingredients are well known to those of ordinary skill in the art and Koverech et al. discloses that betamethasone sodium phosphate retains pharmaceutical activity. There is no evidence of record as to the criticality of the particular salt form used in the claimed method of treating dry eye disease.
Claim(s) 19 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Karolchyl et al., Brady et al. and Lienert et al. as applied to claims 10, 11 and 13 – 18 above, and further in view of Lindstrom (US 7,820,639) and Matsumuru et al. (US 2010/0137252).
Karolchyl et al., Brady et al. and Lienert et al. are discussed above.
An additional step of administration of a lubricating composition such as recited in claim 20 is not disclosed.
Lindstrom discloses ophthalmic compositions that comprise a lubricant, a deturgescent agent, a glycosaminoglycan and water (whole document, e.g., abstract) that may be useful for rehabilitating stressed or damaged ocular tissue (e.g., an ocular surface) to a normal state (col 4, ln 16 – 20). Such rehabilitating encompasses the treatment of dry eye (col 4, ln 61 – col 5, ln 3). The lubricant is preferably glycerol (col 2, ln 7). The deturgescent agent can be a dextran such as dextran 70 (col 2, ln 12 – 17) and the glycosaminoglycan can be chondroitin or a salt thereof such as chondroitin sulfate (col 2, ln 18 – 28). Additional ingredients including buffers such as phosphates; acids or bases to modulate the pH and tonicity modulating agents can also be present in some embodiments (col 2, ln 29 – 35). Amounts of the various ingredients are discussed at, for example, col 2, ln 53 – 67. The pH of the composition is more preferably from 7.0 – 7.4 (col 3, ln 1 – 3).
Matsumura et al. discloses ophthalmic compositions that are useful as an eye drop for dry eyes or eye dryness (whole document, e.g., title and ¶ [0008]). Additional common active ingredients such as polymers can also be present in the formulation (¶ [0030] onward). Disclosed polymers include dextran and chondroitin sulfate (¶ [0039]) with the mixing ratio of each ingredient being known in the field of ophthalmic compositions (¶ [0042]). Typical ingredients used in the ophthalmic preparations also include surfactants, pH adjusters, tonicity agents, chelating agents and buffering agents (¶ [0044] onward). Disclosed surfactants include poloxamer 407 (¶ [0046]). Disclosed pH adjusters include hydrochloric acid and sodium hydroxide (¶ [0049]). Disclosed tonicity agents include potassium chloride, sodium thiosulfate, disodium hydrogen phosphate (sodium phosphate dibasic), sodium dihydrogen phosphate (sodium phosphate monobasic) and glycerin (¶ [0050]). Discloses chelating agents include tetrasodium edetate and sodium edetate (¶ [0051]). Disclosed buffering agents include phosphate buffers with disodium hydrogen sodium dihydrogen phosphate also being disclosed (¶ [0052]).
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to prepare a lubricating formulation such as in claim 20 that is also applied for the treatment of dry eye along with the therapeutically active containing compositions of Karolchyl et al. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because both types of concentrations are known in the prior art for the treatment of dry eye. “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) MPEP 2144.06. The selection of the particular ingredients from those that are known in the art for compositions for ophthalmic use to treat dry eye and the amounts of those ingredients is within the skill of those of ordinary skill in the art. The amount of a specific ingredient in a composition is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of ordinary skill to determine the optimal amount of each ingredient to add in order to best achieve the desired results based on factors of providing lubrication to an eye suffering from dry eye. There is no evidence of record as to the criticality of the claimed ingredients and/or the amounts of those ingredients.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claim 10 – 20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 9 – 14 and 26 – 28 of copending Application No. 17/582,627 in view of Karolchyl et al. (US 2017/0112936) in view of Brady et al. (WO 2017/196881) and Lienert et al. (Ophthalmology, 2016) optionally further in view of Musunuri et al. (US 2018/0333414) and Lindstrom (US 7,820,639) and Matsumuru et al. (US 2010/0137252). The claims of US’627 recite a post-surgical treatment method, where in the subject suffers from or is at risk of suffering from dry eye (claim 28) by the administration of a betamethasone sodium phosphate, mycophenolic acid and a pharmaceutically acceptable carrier for administration to the eye (claims 9 and 13).
The administration of two different compositions of at least varying betamethasone sodium phosphate is not claimed.
Karolchyl et al., Brady et al. and Lienert et al. are discussed above.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to provide compositions as claimed by US’627 that comprise betamethasone sodium phosphate, mycophenolic acid for the treatment of dry eye and a separate composition with a higher concentration of betamethasone for use when symptoms of dry eye are worse, such as during an episodic flare up. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because the severity of the condition being treated and stage of the disease are factors when determining a therapeutically effective dose. Generally with more severe symptoms, a higher dose of the therapeutically active agent would be administered. As explicitly disclosed by Karolchyl et al., one of ordinary skill in the art can select the active components and optimal concentrations of those ingredients in the compositions that can be used to treat dry eye. The amount of a specific ingredient in a composition is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of ordinary skill to determine the optimal amount of each ingredient to add in order to best achieve the desired results based on factors such as the symptom severity and there is no evidence of record as to the criticality of the claimed compositions. The stage and/or severity of a condition can change over time, at least in some patients as discussed by Lienert et al., rendering obvious the use of a lower dosage of the therapeutically active ingredient if symptoms are steady or improve over time as generally, the lowest dose that provides the desired therapeutic effects are given to minimize the potential for side effects that would generally increase at higher doses. However, a worsening of symptoms can result in the need for a higher dosage of the corticosteroid at least until the symptoms improve, when the composition containing the lower dose can be used again.
The use of a plurality of unit dose containers comprising the compositions with different concentrations a corticosteroid such as betamethasone is not disclosed.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to prepare a kit comprising a number of single-use vials of compositions containing different concentration of the therapeutic agent(s) that are provided for use to treat dry eye in a subject. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because kits comprising multiple sterile, single-use vials are a known package form for topical ophthalmics. As the tray can be provided as a whole, one of ordinary skill in the art would vary the number of vials of the different formulations based on the expected usage of a patient. The ongoing treatment in the absence of more severe symptoms could be the composition applied most often so more vials of that composition would be provided with a lower number of the composition with a higher concentration of therapeutic agent for when the patient experiences more severe symptoms.
An additional step of administration of a lubricating composition such as recited in claim 20 is not disclosed.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to prepare a lubricating formulation such as in claim 20 that is also applied for the treatment of dry eye along with the therapeutically active compositions of US’627. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because both types of concentrations are known in the prior art for the treatment of dry eye. “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) MPEP 2144.06. The selection of the particular ingredients from those that are known in the art for compositions for ophthalmic use to treat dry eye and the amounts of those ingredients is within the skill of those of ordinary skill in the art. The amount of a specific ingredient in a composition is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of ordinary skill to determine the optimal amount of each ingredient to add in order to best achieve the desired results based on factors of providing lubrication to an eye suffering from dry eye. There is no evidence of record as to the criticality of the claimed ingredients and/or the amounts of those ingredients.
This is a provisional nonstatutory double patenting rejection.
Claims 10 – 20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 10 - 28 of copending Application No. 18/100,505 in view of Karolchyl et al. (US 2017/0112936) in view of Brady et al. (WO 2017/196881) and Lienert et al. (Ophthalmology, 2016) optionally further in view of Musunuri et al. (US 2018/0333414) and Lindstrom (US 7,820,639) and Matsumuru et al. (US 2010/0137252). The claims of US’550 recite a post-surgical treatment method with an active step of administration of a composition comprising betamethasone or a salt thereof and/or mycophenolic acid (claims 10 and 14) and claims to such composition (claims 20 – 25). The betamethasone salt can be betamethasone sodium phosphate (claim 17).
That the composition is administered to treat dry eye and the use of two different compositions of at least varying betamethasone sodium phosphate concentration is not claimed.
Karolchyl et al., Brady et al. and Lienert et al. are discussed above.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to provide compositions as claimed by US’505 that comprise betamethasone sodium phosphate, mycophenolic acid for the treatment of dry eye and a separate composition with a higher concentration of betamethasone for use when symptoms of dry eye are worse, such as during an episodic flare up. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because the severity of the condition being treated and stage of the disease are factors when determining a therapeutically effective dose. Generally with more severe symptoms, a higher dose of the therapeutically active agent would be administered. As explicitly disclosed by Karolchyl et al., one of ordinary skill in the art can select the active components and optimal concentrations of those ingredients in the compositions that can be used to treat dry eye. The amount of a specific ingredient in a composition is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of ordinary skill to determine the optimal amount of each ingredient to add in order to best achieve the desired results based on factors such as the symptom severity and there is no evidence of record as to the criticality of the claimed compositions. The stage and/or severity of a condition can change over time, at least in some patients as discussed by Lienert et al., rendering obvious the use of a lower dosage of the therapeutically active ingredient if symptoms are steady or improve over time as generally, the lowest dose that provides the desired therapeutic effects are given to minimize the potential for side effects that would generally increase at higher doses. However, a worsening of symptoms can result in the need for a higher dosage of the corticosteroid at least until the symptoms improve, when the composition containing the lower dose can be used again.
The use of a plurality of unit dose containers comprising the compositions with different concentrations a corticosteroid such as betamethasone is not disclosed.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to prepare a kit comprising a number of single-use vials of compositions containing different concentration of the therapeutic agent(s) that are provided for use to treat dry eye in a subject. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because kits comprising multiple sterile, single-use vials are a known package form for topical ophthalmics. As the tray can be provided as a whole, one of ordinary skill in the art would vary the number of vials of the different formulations based on the expected usage of a patient. The ongoing treatment in the absence of more severe symptoms could be the composition applied most often so more vials of that composition would be provided with a lower number of the composition with a higher concentration of therapeutic agent for when the patient experiences more severe symptoms.
An additional step of administration of a lubricating composition such as recited in claim 20 is not disclosed.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to prepare a lubricating formulation such as in claim 20 that is also applied for the treatment of dry eye along with the therapeutically active compositions of US’505. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because both types of concentrations are known in the prior art for the treatment of dry eye. “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) MPEP 2144.06. The selection of the particular ingredients from those that are known in the art for compositions for ophthalmic use to treat dry eye and the amounts of those ingredients is within the skill of those of ordinary skill in the art. The amount of a specific ingredient in a composition is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of ordinary skill to determine the optimal amount of each ingredient to add in order to best achieve the desired results based on factors of providing lubrication to an eye suffering from dry eye. There is no evidence of record as to the criticality of the claimed ingredients and/or the amounts of those ingredients.
This is a provisional nonstatutory double patenting rejection.
Claims 10 – 20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 - 15 of U.S. Patent No. 11,766,421 in view of Karolchyl et al. (US 2017/0112936) in view of Brady et al. (WO 2017/196881) and Lienert et al. (Ophthalmology, 2016) optionally further in view of Musunuri et al. (US 2018/0333414) and Lindstrom (US 7,820,639) and Matsumuru et al. (US 2010/0137252). The claims of US’421 recite a pharmaceutical composition for topical application to the eye comprising mycophenolic acid, optionally a lubricating agent, chondroitin sulfate and a pharmaceutically acceptable carrier (claims 1 and 7). The compositions can further comprise a corticosteroid such as betamethasone sodium phosphate (claims 11 and 12). The composition can be packaged as eye drops (claims 6 and 15).
That the composition is administered to treat dry eye and the use of two different compositions of at least varying betamethasone sodium phosphate concentration is not claimed.
Karolchyl et al., Brady et al. and Lienert et al. are discussed above.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to provide compositions as claimed by US’421 that comprise betamethasone sodium phosphate, mycophenolic acid for the treatment of dry eye and a separate composition with a higher concentration of betamethasone for use when symptoms of dry eye are worse, such as during an episodic flare up. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because the severity of the condition being treated and stage of the disease are factors when determining a therapeutically effective dose. Generally with more severe symptoms, a higher dose of the therapeutically active agent would be administered. As explicitly disclosed by Karolchyl et al., one of ordinary skill in the art can select the active components and optimal concentrations of those ingredients in the compositions that can be used to treat dry eye. The amount of a specific ingredient in a composition is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of ordinary skill to determine the optimal amount of each ingredient to add in order to best achieve the desired results based on factors such as the symptom severity and there is no evidence of record as to the criticality of the claimed compositions. The stage and/or severity of a condition can change over time, at least in some patients as discussed by Lienert et al., rendering obvious the use of a lower dosage of the therapeutically active ingredient if symptoms are steady or improve over time as generally, the lowest dose that provides the desired therapeutic effects are given to minimize the potential for side effects that would generally increase at higher doses. However, a worsening of symptoms can result in the need for a higher dosage of the corticosteroid at least until the symptoms improve, when the composition containing the lower dose can be used again.
The use of a plurality of unit dose containers comprising the compositions with different concentrations a corticosteroid such as betamethasone is not disclosed.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to prepare a kit comprising a number of single-use vials of compositions containing different concentration of the therapeutic agent(s) that are provided for use to treat dry eye in a subject. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because kits comprising multiple sterile, single-use vials are a known package form for topical ophthalmics. As the tray can be provided as a whole, one of ordinary skill in the art would vary the number of vials of the different formulations based on the expected usage of a patient. The ongoing treatment in the absence of more severe symptoms could be the composition applied most often so more vials of that composition would be provided with a lower number of the composition with a higher concentration of therapeutic agent for when the patient experiences more severe symptoms.
An additional step of administration of a lubricating composition such as recited in claim 20 is not disclosed.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to prepare a lubricating formulation such as in claim 20 that is also applied for the treatment of dry eye along with the therapeutically active compositions of US’421. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because both types of concentrations are known in the prior art for the treatment of dry eye. “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) MPEP 2144.06. The selection of the particular ingredients from those that are known in the art for compositions for ophthalmic use to treat dry eye and the amounts of those ingredients is within the skill of those of ordinary skill in the art. The amount of a specific ingredient in a composition is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of ordinary skill to determine the optimal amount of each ingredient to add in order to best achieve the desired results based on factors of providing lubrication to an eye suffering from dry eye. There is no evidence of record as to the criticality of the claimed ingredients and/or the amounts of those ingredients.
Claims 10 – 20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 - 23 of U.S. Patent No. 12,070,442 in view of Karolchyl et al. (US 2017/0112936) in view of Brady et al. (WO 2017/196881) and Lienert et al. (Ophthalmology, 2016) optionally further in view of Musunuri et al. (US 2018/0333414) and Lindstrom (US 7,820,639) and Matsumuru et al. (US 2010/0137252). The claims of US’442 recite pharmaceutical compositions of mycophenolic acid or a pharmaceutically acceptable salt thereof, betamethasone or a pharmaceutically acceptable salt thereof and a carrier (claim 1) and methods of treating ocular surface diseases by administering a composition as claimed (claims 18 - 22). The betamethasone pharmaceutically acceptable salt can be the sodium phosphate salt (claim 3).
That the composition is administered to treat dry eye and the use of two different compositions of at least varying betamethasone sodium phosphate concentration is not claimed.
Karolchyl et al., Brady et al. and Lienert et al. are discussed above.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to provide compositions as claimed by US’442 that comprise betamethasone sodium phosphate, mycophenolic acid for the treatment of dry eye and a separate composition with a higher concentration of betamethasone for use when symptoms of dry eye are worse, such as during an episodic flare up. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because the severity of the condition being treated and stage of the disease are factors when determining a therapeutically effective dose. Generally with more severe symptoms, a higher dose of the therapeutically active agent would be administered. As explicitly disclosed by Karolchyl et al., one of ordinary skill in the art can select the active components and optimal concentrations of those ingredients in the compositions that can be used to treat dry eye. The amount of a specific ingredient in a composition is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of ordinary skill to determine the optimal amount of each ingredient to add in order to best achieve the desired results based on factors such as the symptom severity and there is no evidence of record as to the criticality of the claimed compositions. The stage and/or severity of a condition can change over time, at least in some patients as discussed by Lienert et al., rendering obvious the use of a lower dosage of the therapeutically active ingredient if symptoms are steady or improve over time as generally, the lowest dose that provides the desired therapeutic effects are given to minimize the potential for side effects that would generally increase at higher doses. However, a worsening of symptoms can result in the need for a higher dosage of the corticosteroid at least until the symptoms improve, when the composition containing the lower dose can be used again.
The use of a plurality of unit dose containers comprising the compositions with different concentrations a corticosteroid such as betamethasone is not disclosed.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to prepare a kit comprising a number of single-use vials of compositions containing different concentration of the therapeutic agent(s) that are provided for use to treat dry eye in a subject. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because kits comprising multiple sterile, single-use vials are a known package form for topical ophthalmics. As the tray can be provided as a whole, one of ordinary skill in the art would vary the number of vials of the different formulations based on the expected usage of a patient. The ongoing treatment in the absence of more severe symptoms could be the composition applied most often so more vials of that composition would be provided with a lower number of the composition with a higher concentration of therapeutic agent for when the patient experiences more severe symptoms.
An additional step of administration of a lubricating composition such as recited in claim 20 is not disclosed.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to prepare a lubricating formulation such as in claim 20 that is also applied for the treatment of dry eye along with the therapeutically active compositions of US’442. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because both types of concentrations are known in the prior art for the treatment of dry eye. “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) MPEP 2144.06. The selection of the particular ingredients from those that are known in the art for compositions for ophthalmic use to treat dry eye and the amounts of those ingredients is within the skill of those of ordinary skill in the art. The amount of a specific ingredient in a composition is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of ordinary skill to determine the optimal amount of each ingredient to add in order to best achieve the desired results based on factors of providing lubrication to an eye suffering from dry eye. There is no evidence of record as to the criticality of the claimed ingredients and/or the amounts of those ingredients.
Conclusion
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/Nissa M Westerberg/Primary Examiner, Art Unit 1618