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 the Claims
The listing of claims filed 15 November 2023 has been examined. Claims 1-8 are pending.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 15 November 2023 is acknowledged and has been considered.
Priority
The instant application was received 15 November 2023; it is a national stage application of PCT/EP2022/064944, filed 01 June 2022. The instant application claims foreign priority to SE2130150-2, filed 01 June 2021. Acknowledgement is made of Applicant’s claim for foreign priority and certified copies of the priority documents have been received.
Claim Objections
Claims 3-4 are objected to because of the following informalities: Claims 3-4 recite “said formulation.” Applicant has previously recited the formulation as a “topical formulation.” For consistency, Examiner requests all instances of the same formulation be referred to using the same language. Accordingly, Examiner suggests amending “said formulation” in claims 3-4 to “said topical formulation” or similar. Appropriate correction is requested.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 5-6 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 5 recites, “…for use in… a skin disease,” and claim 6 recites, “…for use in… an inflammatory skin disease.” These are broad genera and, according to their broadest reasonable interpretation, include any skin disease (Claim 5) and any inflammatory skin disease (Claim 6). For example, skin diseases which can be characterized by inflammation include skin cancer, viral infections (e.g., shingles), bacterial infections (e.g., methicillin-resistant Staphylococcus aureus), and fungal infections (e.g., ringworm). However, the only skin diseases disclosed in the instant application are Netherton syndrome, atopic dermatitis, contact dermatitis, eczema, psoriasis, acne, epidermal keratosis, acanthosis, epidermal inflammation, dermal inflammation, pruritus, and Rosacea (Claim 7; p. 7, Lines 16-19). Thus, the instant application lacks sufficient variety in the disclosed skin diseases to reflect the variance within the genera which are encompassed by the terms “skin disease” and “inflammatory skin disease.” Furthermore, based on the limited number of examples provided for the claimed genera, “skin disease” and “inflammatory skin disease,” a representative number of examples to support the claimed genera is lacking and a person having ordinary skill in the art (PHOSITA) would conclude that Applicant is not in possession of the claims, as currently recited.
Claims 7-8 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
While the specification (in view of the prior art) reasonably provides enablement for the treatment of Netherton syndrome by managing its associated symptoms, it does not reasonably provide enablement for the prophylaxis or prevention of Netherton syndrome.
MPEP § 2164.01(a) explains how enablement for the claimed invention can be analyzed:
In order to determine compliance with the enablement requirement of 35 U.S.C. 112(a), the Federal Circuit developed a framework of factors in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), referred to as the Wands factors to assess whether any necessary experimentation required by the specification is “reasonable” or is “undue.” These factors include, but are not limited to:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
The Wands factors are analyzed with respect to the claimed elements in turn below.
The breadth of the claim is broad in scope, as it extends to any method by which inflammatory diseases, including Netherton syndrome, can be prevented using the claimed topical formulation. Specifically, claim 7 recites, “A topical formulation according to claim 1 for use in prophylaxis, prevention, and/or treatment of an inflammatory skin disease selected from Netherton syndrome, atopic dermatitis, contact dermatitis, eczema, psoriasis, acne, epidermal hyperkeratosis, acanthosis, epidermal inflammation, dermal inflammation, and pruritus and Rosacea.”
The terms “prophylaxis” and “prevention” are not given alternate definitions in the instant specification. Thus, these terms will be interpreted in accordance with their plain meaning (MPEP 2111.01(I)). The Oxford English Dictionary defines “prophylaxis” as, “Treatment intended to prevent disease; a particular treatment of this nature. Hence more widely: precautionary action,” and defines “prevention” as, “The action of keeping from happening or making impossible an anticipated event or intended act.” Based on this interpretation, the breadth of the claims is any manner by which the claimed topical formulation can be administered to a subject for the prevention or prophylaxis of an inflammatory skin disease, including Netherton syndrome, atopic dermatitis, contact dermatitis, eczema, psoriasis, acne, epidermal hyperkeratosis, acanthosis, epidermal inflammation, dermal inflammation, pruritus, and Rosacea. Furthermore, the topical formulation may be administered, “…to a subject in need of such treatment” (p. 7, Lines 12-14).
The nature of the invention generally relates to the pharmaceutical arts and more specifically to a topical formulation for use in prophylaxis, prevention, and/or treatment of an inflammatory skin disease, including Netherton syndrome.
The state of the prior art can be ascertained by reviewing the Background of the Specification and relevant literature. Netherton syndrome is a genetic disease caused by mutations in the spink gene, which encodes LEKTI (Instant Specification at p. 3, Lines 1-5). Generally, in order to treat a disease, one of skill in the art must identify a biological target for affecting the disease, demonstrate a first drug candidate some way modulates the normal processes of the biological target, and demonstrate that a subject would benefit from such modulation without detrimental side effects. Typically, the process includes in vitro laboratory screening, in vivo testing, and clinical testing. Once that process has been successfully completed by the first drug candidate, subsequent drug candidates can benefit from the established proof of concept if a substantial correlation can be established between the first drug candidate and the subsequent drug candidates.
In order to prevent a disease, one of skill in the art would need to identify the subjects likely to acquire such as disease, carry out the claimed invention (e.g., administer the claimed compound/composition), and demonstrate the subject did not have any cells infected by the pathogen and/or demonstrate the subject did not develop the disease as a result of the administration of the compound/composition.
With respect to the instant application, the state of the art can be informed by prior studies linking increased KLK7 activity to inflammatory skin diseases and demonstrating 6-ethoxy-7-methoxy-2-(2-methylsulfanylphenyl)-3,1-benzoxazin-4-one is a KLK7 inhibitor (Instant Specification at p. 4, Line 9 – p. 4, Line 2) as well as other related information. Examiner is not aware of any evidence that 6-ethoxy-7-methoxy-2-(2-methylsulfanylphenyl)-3,1-benzoxazin-4-one can prevent a subject from developing Netherton syndrome or that a subject did not develop Netherton syndrome as a result of the administration of the topical formulation.
The level of one of ordinary skill may be found by inquiring into: (i) the type of problems encountered in the art; (ii) prior art solutions to those problems; (iii) the rapidity with which innovations are made; (iv) the sophistication of the technology; and (v) the education level of active workers in the field. Custom Accessories, Inc. v. Jeffrey-Allan Industries, Inc., 807 F.2d 855, 962 (Fed. Cir. 1986). All of the factors may not be present in every case, and one or more of them may predominate. Envtl. Designs, Ltd. v. Union Oil Co., 713 F.2d 693, 696 (Fed. Cir. 1983). Based on the typically high education level of workers in the pharmaceutical art and the high degree of sophistication required to solve problems encountered in the art, Examiner finds a person having ordinary skill in the art would have at least a college degree in chemistry, biology, biochemistry, pharmacology, or a related field, and several years of experience.
The level of predictability in the art is generally unpredictable. The relevant art requires each potential drug candidate to be assessed for physiological activity. In re Fisher, 427 F.2d 833, 166 USPQ 18, 24 (CCPA 1970). The more unpredictable an area is the more specific disclosure is necessary to satisfy the statutory requirement. MPEP § 2164.02(II) explains that a correlation between the claimed invention and the evidence provided in an application, along with a correlation between the evidence and the models recognized in the art, are required:
“Correlation” as used herein refers to the relationship between in vitro or in vivo animal model assays and a disclosed or a claimed method of use. An in vitro or in vivo animal model example in the specification, in effect, constitutes a “working example” if that example “correlates” with a disclosed or claimed method invention. If there is no correlation, then the examples do not constitute “working examples.” In this regard, the issue of “correlation” is also dependent on the state of the prior art. In other words, if the art is such that a particular model is recognized as correlating to a specific condition, then it should be accepted as correlating unless the examiner has evidence that the model does not correlate. Even with such evidence, the examiner must weigh the evidence for and against correlation and decide whether one skilled in the art would accept the model as reasonably correlating to the condition. In re Brana, 51 F.3d 1560, 1566, 34 USPQ2d 1436, 1441 (Fed. Cir. 1995) (reversing a USPTO decision based on finding that in vitro data did not support in vivo applications).
Further, treatments may be effective for some subjects and ineffective for other subjects. Thus, each candidate for pharmaceutical medicine must be evaluated on its own even when a nexus to an existing drug or class of drugs has been established.
The amount of direction provided by the inventor relates to the solubility properties of 6-ethoxy-7-methoxy-2-(2-methylsulfanylphenyl)-3,1-benzoxazin-4-one, specifically its solubility (p. 9, Example 1), and formulations comprising 6-ethoxy-7-methoxy-2-(2-methylsulfanylphenyl)-3,1-benzoxazin-4-one, specifically creams (p. 10-12, Examples 2-4).
The existence of working examples relates to the solubility properties of 6-ethoxy-7-methoxy-2-(2-methylsulfanylphenyl)-3,1-benzoxazin-4-one, specifically its solubility (p. 9, Example 1), and formulations comprising 6-ethoxy-7-methoxy-2-(2-methylsulfanylphenyl)-3,1-benzoxazin-4-one, specifically creams (p. 10-12, Examples 2-4). The instant specification indicates increased kallikrein 7 (KLK7) activity has been linked to inflammatory skin diseases and so KLK7 inhibitors, like 6-ethoxy-7-methoxy-2-(2-methylsulfanylphenyl)-3,1-benzoxazin-4-one, have potential in treating inflammatory skin diseases (p. 3). There are no working examples demonstrating the in vitro or in vivo activity of the claimed topical formulation or its efficacy in reducing inflammation in a subject.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure is extensive, as it includes in vitro and in vivo screening for each specific disease, particularly Netherton syndrome.
Scope of Enablement Conclusion - In view of the Wands factors discussed above, the disclosure of the instant application does not reasonably enable a PHOSITA to use the full scope of the claimed invention since it would be unclear to a PHOSITA how administering the claimed topical formulation would prevent Netherton syndrome, as opposed to simply manage its symptoms, and the experimentation required to enable the full scope of the claims would not be reasonable. Furthermore, the nature of the invention is sophisticated, the state of the prior art is not established for how the claimed topical formulation could prevent Netherton syndrome, the breadth of the claims is broad in scope, the art is unpredictable, and the working examples are directed to the solubility of 6-ethoxy-7-methoxy-2-(2-methylsulfanylphenyl)-3,1-benzoxazin-4-one and cream formulations containing 6-ethoxy-7-methoxy-2-(2-methylsulfanylphenyl)-3,1-benzoxazin-4-one, rather than biological properties that correlate to the claimed methods. Accordingly, when the evidence is considered as a whole, undue experimentation would be required to practice the full scope of the claimed invention. Examiner recommends amending the claims to the prophylaxis, prevention, and treatment of diseases that are supported by the disclosure.
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.
Claims 1 and 5-8 are rejected under 35 U.S.C. 103 as being unpatentable over Wägberg (WO 2015/112081 A1; IDS dated 15 November 2023, Cite No. 1) in view of Mercier (US 7,488,471 B2).
Regarding claim 1, Wägberg teaches substituted 3,1-benzoxazin-4-ones, including 6-ethoxy-7-methoxy-2-(2-methylsulfanylphenyl)-3,1-benzoxazin-4-one (p. 4, Bottom Paragraph, Formula I; p. 16, Claim 2), as skin protease inhibitors (p. 1, Top Paragraph). Among the substituted 3,1-benzoxazin-4-ones disclosed by Wägberg, 6-ethoxy-7-methoxy-2-(2-methylsulfanylphenyl)-3,1-benzoxazin-4-one was identified as exhibiting the desired selectivity for the skin proteases kallikrein 5 (KLK5), KLK7, and KLK14 (p. 12, Table 1; p. 14, Top Paragraph).
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Figure 1 | 6-ethoxy-7-methoxy-2-(2-methylsulfanylphenyl)-3,1-benzoxazin-4-one chemical structure drawn in JChem.
Wägberg indicates these compounds, or pharmaceutically acceptable salts thereof, may be included in a pharmaceutical composition alongside adjuvants, diluents, and carriers (p. 5, Paragraph 6) and the resultant composition can be used in treating skin diseases (p. 6, Paragraph 7). Wägberg suggests the pharmaceutical composition may be administered by conventional administration routes such as oral or topical administration (p. 6, Bottom Paragraph – p. 7, Paragraphs 1-2) and include solid or liquid carriers (p. 7, Paragraph 3). Liquid compositions include solutions, suspensions, and emulsions and may include aqueous polyethylene glycol (p. 8, Paragraph 3). Wägberg discloses the pharmaceutical composition may include 0.05-99% weight or 0.10-50% weight of the substituted 3,1-benzoxazin-4-one compound depending on the administration method (p. 8, Paragraph 5) and suggests a skilled artisan could determine the appropriate therapeutically effective amount (p. 8, Paragraph 6).
Wägberg does not explicitly teach an oil-in-water emulsion comprising about 60-70% (w/w) oil phase and about 25-40% (w/w) aqueous phase.
Mercier teaches clear or transparent oil-in-water emulsions for cosmetic and pharmaceutical use comprising an oil phase and an aqueous phase (Abstract; Col. 2, Lines 31-35). Additionally, Mercier teaches emulsions are unstable and have a tendency to separate into the oil and aqueous phases, so it’s important to incorporate emulsifiers into the emulsion to help create and maintain the uniform fine dispersion of the phases (Col. 1, Lines 10-21). Mercier discloses the oil phase comprises at least one lipophilic solvent and can also contain a lipophilic co-solvent such as fatty acid esters, liquid branched chain fatty alcohols from 16-20 carbon atoms in length, and triglycerides, with the preferred triglyceride being carprylic/capric triglyceride (Col. 3, Lines 39-42 and 54-58). Mercier suggests the oil phase comprise about 30-70% by weight of the emulsion (Col. 3, Lines 60-62). The aqueous phase includes water and water-soluble ingredients and can include polyols like polyethylene glycol (Col. 3, Lines 66-67 – Col. 4, Lines 1-7). Mercier suggests the polyol in the aqueous phase comprise about 10-35% of the total composition (Col. 4, Lines 14-18).
Mercier does not explicitly teach the compound 6-ethoxy-7-methoxy-2-(2-methylsulfanylphenyl)-3,1-benzoxazin-4-one.
Prior to the filing of the instant application, a person having ordinary skill in the art (PHOSITA) following the teachings of Wägberg would have found it prima facie obvious to make an oil-in-water emulsion containing 6-ethoxy-7-methoxy-2-(2-methylsulfanylphenyl)-3,1-benzoxazin-4-one based on the teachings of Mercier. Wägberg discloses this compound may be included in an emulsion and explains its utility in treating various skin diseases. Furthermore, Wägberg indicates a pharmaceutical composition can contain at least 0.05% weight of a substituted 3,1-benzoxazin-4-one compound. Mercier teaches an oil-in-water emulsion having an oil phase comprising about 30-70% by weight and an aqueous phase comprising about 10-35% by weight of the emulsion composition, which partially overlaps the ranges recited by instant claim 1. Since Wägberg discloses substituted 3,1-benzoxazin-4-one compounds like 6-ethoxy-7-methoxy-2-(2-methylsulfanylphenyl)-3,1-benzoxazin-4-one can be administered as emulsions and Mercier discloses an oil-in-water emulsion, a skilled artisan would have been motivated to incorporate 6-ethoxy-7-methoxy-2-(2-methylsulfanylphenyl)-3,1-benzoxazin-4-one into the composition disclosed by Mercier because Mercier indicates oil-in-water emulsions can be advantageous since water-soluble ingredients can be easily added into the aqueous phase and are bioavailable soon after applying the composition (Col. 2, Lines 7-11). Furthermore, a PHOSITA would have known to optimize the ratio between the oil and aqueous phases to achieve the desired consistency of the topical composition while simultaneously minimizing any potential instability in the emulsion (MPEP 2144.05(II)).
Regarding claims 5-8, Wägberg in view of Mercier teaches all of the claimed elements as stated above. Furthermore, Wägberg teaches 6-ethoxy-7-methoxy-2-(2-methylsulfanylphenyl)-3,1-benzoxazin-4-one selectively inhibits the skin proteases KLK7, KLK5, and KLK14, which are involved in the pathophysiology of inflammatory skin diseases like Netherton syndrome (p. 5, Top Paragraph). Wägberg states this compound can be used, “…in the prophylaxis, prevention, and/or treatment of a skin disease” (p. 5, Paragraph 5; p. 16, Claim 5). The skin disease may be an inflammatory skin disease, Netherton syndrome, atopic dermatitis, contact dermatitis, eczema, psoriasis, acne, epidermal hyperkeratosis, acanthosis, epidermal inflammation, dermal inflammation, or pruritus (p. 16-17, Claims 10-12; p. 6, Paragraphs 1-3).
Prior to the filing of the instant application, a PHOSITA following the teachings of Wägberg would have found it prima facie obvious to use 6-ethoxy-7-methoxy-2-(2-methylsulfanylphenyl)-3,1-benzoxazin-4-one in the prophylaxis, prevention, and/or treatment of the skin diseases recited in instant claims 5-8 in a topical formulation comprising an oil-in-water emulsion as described by Mercier because Wägberg indicates this compound is useful in treating skin diseases including Netherton syndrome and other inflammatory skin diseases.
Claims 2-4 are rejected under 35 U.S.C. 103 as being unpatentable over Wägberg (WO 2015/112081 A1; IDS dated 15 November 2023, Cite No. 1) in view of Mercier (US 7,488,471 B2) and Tamarkin (US 9,265,725 B2).
Regarding claims 2-4, , Wägberg in view of Mercier teaches all of the claimed elements as stated above. Furthermore, Wägberg discloses aqueous solutions may involve dissolving the active ingredient in water and adding other components such as stabilizers and thickening agents (p. 8, Paragraph 4). Additionally, Mercier provides example compositions which include caprylic/capric triglyceride in amounts between 11.45-15.95% (w/w), polyethylene glycol (PEG-8) in amounts between 12.00-13.00% (w/w), and NaOH (18% Sol.) to alter the pH in amounts between 1.15-1.35% (w/w) (Col. 5, Example 1; Col. 6, Example 2; Col. 8, Example 4; Col. 6, Lines 20-24).
However, the combination of Wägberg and Mercier does not explicitly teach a formulation containing 6-ethoxy-7-methoxy-2-(2-methylsulfanylphenyl)-3,1-benzoxazin-4-one in addition to ≥ 50% (w/w) medium chain triglyceride oil (MCT), isopropyl myristate (IPM) , cetostearyl alcohol, polyethylene glycol hexadecyl ether, and citrate buffer.
Tamarkin teaches foaming pharmaceutical and cosmetic topical compositions (Col. 1, Lines 58-61), including emulsion-based foams (Col. 2, Lines 13-17). Tamarkin indicates oil-containing foams are preferred in skin therapy because oil promotes skin protection and moisturization as well as improves the formulation’s therapeutic effect (Col. 2, Lines 17-20). Tamarkin indicates in some embodiments the composition contains an organic carrier, which can be triglycerides, medium chain triglyceride (MCT) oil, capric/caprylic triglycerides, and alkyl esters of fatty acids like isopropyl myristate (Col. 9, Lines 62-67 – Col. 10, Lines 1-17). Tamarkin indicates in some embodiments the composition contains a surface active agent like cetearyl alcohol, which is also known as cetostearyl alcohol, or polyethylene glycol cetyl ether, which is also known as polyethylene glycol hexadecyl ether (Col. 7, Lines 35-36 and 46). Tamarkin indicates in some embodiments the composition contains a buffering agent or a pH-adjusting agent (Col. 10, Line 65; Col. 11, Line 2). Furthermore, Tamarkin discloses using NaOH to adjust the pH in a foaming composition (Col. 49-50, Example 10).
Tamarkin does not explicitly teach the compound 6-ethoxy-7-methoxy-2-(2-methylsulfanylphenyl)-3,1-benzoxazin-4-one or the exact formulations recited in instant claims 2-4.
Prior to the filing of the instant application, a PHOSITA following the teachings of Wägberg and Mercier would have found it prima facie obvious to prepare a formulation containing the components disclosed by Tamarkin. While a citrate buffer is not expressly recited by Tamarkin, Tamarkin does indicate buffering agents may be included in the composition and a skilled artisan would recognize citrate buffer as a buffering agent. Thus, Tamarkin teaches topical compositions may contain all the ingredients recited by instant claims 2-4 except 6-ethoxy-7-methoxy-2-(2-methylsulfanylphenyl)-3,1-benzoxazin-4-one. A PHOSITA would have been motivated to incorporate 6-ethoxy-7-methoxy-2-(2-methylsulfanylphenyl)-3,1-benzoxazin-4-one into an oil-in-water emulsion comprising an oil and aqueous phase containing ingredients disclosed by Tamarkin because Wägberg, Mercier, and Tamarkin all disclose topical formulations. Additionally, Tamarkin states oil-containing formulations are needed since these formulations allow beneficial compounds to be easily delivered to the skin and are relatively non-irritating, making such formulations appropriate for individuals with sensitive skin and/or eyes (Col 2, Lines 47-52). Furthermore, a PHOSITA would have known to optimize the ingredient ratios to achieve the desired consistency of the topical composition while simultaneously minimizing any potential instability in the emulsion (MPEP 2144.05(II)).
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.
Claims 1-8 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 13 of U.S. Patent No. 10,072,024 in view of Mercier (US 7,488,471 B2) and Tamarkin (US 9,265,725 B2).
Patent ‘024 claims a composition containing the compound 6-ethoxy-7-methoxy-2-(2-methylsulfanylphenyl)-3,1-benzoxazin-4-one (Claim 10) for the treatment of inflammatory skin diseases. Claim 13, which depends on claim 10, claims the composition in a formulation for topical administration.
Patent ‘024 does not recite an oil-in-water emulsion containing 6-ethoxy-7-methoxy-2-(2-methylsulfanylphenyl)-3,1-benzoxazin-4-one.
Mercier teaches clear or transparent oil-in-water emulsions for cosmetic and pharmaceutical use comprising an oil phase and an aqueous phase (Abstract; Col. 2, Lines 31-35). Additionally, Mercier teaches emulsions are unstable and have a tendency to separate into the oil and aqueous phases, so it’s important to incorporate emulsifiers into the emulsion to help create and maintain the uniform fine dispersion of the phases (Col. 1, Lines 10-21). Mercier discloses the oil phase comprises at least one lipophilic solvent and can also contain a lipophilic co-solvent such as fatty acid esters, liquid branched chain fatty alcohols from 16-20 carbon atoms in length, and triglycerides, with the preferred triglyceride being carprylic/capric triglyceride (Col. 3, Lines 39-42 and 54-58). Mercier suggests the oil phase comprise about 30-70% by weight of the emulsion or, preferably, about 40-50% by weight (Col. 3, Lines 60-62). The aqueous phase includes water and water-soluble ingredients and can include polyols like polyethylene glycol (Col. 3, Lines 66-67 – Col. 4, Lines 1-7). Mercier suggests the polyol in the aqueous phase comprise about 10-35% of the total composition or, preferably, about 18-25% (Col. 4, Lines 14-18).
Tamarkin teaches foaming pharmaceutical and cosmetic topical compositions (Col. 1, Lines 58-61), including emulsion-based foams (Col. 2, Lines 13-17). Tamarkin indicates oil-containing foams are preferred in skin therapy because oil promotes skin protection and moisturization as well as improves the formulation’s therapeutic effect (Col. 2, Lines 17-20). Tamarkin indicates in some embodiments the composition contains an organic carrier, which can be triglycerides, medium chain triglyceride (MCT) oil, capric/caprylic triglycerides, and alkyl esters of fatty acids like isopropyl myristate (Col. 9, Lines 62-67 – Col. 10, Lines 1-17). Tamarkin indicates in some embodiments the composition contains a surface active agent like cetearyl alcohol, which is also known as cetostearyl alcohol, or polyethylene glycol cetyl ether, which is also known as polyethylene glycol hexadecyl ether (Col. 7, Lines 35-36 and 46). Tamarkin indicates in some embodiments the composition contains a buffering agent or a pH-adjusting agent (Col. 10, Line 65; Col. 11, Line 2). Furthermore, Tamarkin discloses using NaOH to adjust the pH in a foaming composition (Col. 49-50, Example 10).
The combination of Mercier and Tamarkin does not explicitly teach the compound 6-ethoxy-7-methoxy-2-(2-methylsulfanylphenyl)-3,1-benzoxazin-4-one or the exact formulations recited in instant claims 2-4.
A PHOSITA would have had a reasonable expectation of success in selecting the oil-in-water emulsion disclosed by Mercier and ingredients disclosed by Tamarkin when preparing a composition containing the compound 6-ethoxy-7-methoxy-2-(2-methylsulfanylphenyl)-3,1-benzoxazin-4-one for topical administration because both Mercier and Tamarkin discuss the advantages associated with oil-containing compositions. For example, such compositions allow beneficial active ingredients to be readily delivered to the skin (Mercier, Col. 2, Lines 7-11; Tamarkin, Col. 2, Lines 47-52).
Because claims 1-8 in the instant application would have been obvious over claim 13 of U.S. Patent No. 10,072,024 in view of Mercier and Tamarkin, claims 1-8 in the instant application are not patently distinct from claim 13 of U.S. Patent No. 10,072,024.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRIANNA L BAUER whose telephone number is (571)272-5752. The examiner can normally be reached 8am-5pm.
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, ADAM C MILLIGAN can be reached at (571)270-7674. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/B.L.B./Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623
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