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 .
Response to Amendments
Applicant’s amendment to the claims of April 28, 2026, in response to the Office Action of October 28, 2025, are acknowledged.
Response to Arguments
Applicant has added claims directed to treating pityriasis rubra pilaris and acne. The examiner applies art to address these conditions. The § 112 rejections and claim objections are withdrawn in view of the amendments and cancelation of claims.
The examiner notes that Warren et al., (US2022/0062379) (of record) teaches benzamil to provide substantial inhibition of TNF, IL6, and IL1β in a dose dependent manner. See Table 5, below.
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Werther et al., (US2003/0096769) teaches treating and preventing inflammatory skin disorders by administering an inhibitor of a one of the following: tumor necrosis factor alpha, IL-1, and IL-6 among a 9 total mediators. See prior art claims 1 and 2. Further, claim 5 provides that such method can treating specific conditions, including pityriasis rubra pilaris among a total of approximately 10 conditions. Compositions can be applied topically. See par.’s 26, 29, prior art claim 23.
Kistowska et al., “IL-1b Drives Inflammatory Responses to Propionibacterium acnes In Vitro and In Vivo,” The Society for Investigative Dermatology 2014, teaches: “In mice, inflammation induced by P. acnes is critically dependent on IL-1b and the NLRP3 inflammasome of myeloid cells. These findings show that the commensal P. acnes—by activating the inflammasome—can trigger an innate immune response in the skin, thus establishing the NLRP3-inflammasome and IL-1b as possible therapeutic targets in acne.” Abstract. Kistowska teaches that IL-1β is shown to be abundant in human acne lesions. See p678, 1st par. “Altogether, our data implicate IL-1β as a novel therapeutic target in acne.”
Applicant argues that the cited prior art does not teach the other claimed conditions.
The examiner notes that Warren teaches treating sarcoidosis (par. 17), lichen planus, alopecia areata, dermatomyositis, hyrdradenitis suppurativa, scleroderma, and many others that remain claimed. See par. 12. Benzamil is the preferred agent. See prior art claims 76 and 79, e.g. Prior art claims 19 and 20 are directed to a dermatologic disorder, including many of those claimed.
As such, the examiner notes that Warren teaches treating the claimed conditions with a claimed agent. Applicant’s remaining arguments are moot in view of the amendments to the claims and the application of prior art to address acne and pityriasis rubra pilaris.
The examiner notes if the claimed agent is administered to a claimed subject population as motivated by the prior art, the burden is on Applicant to show: (1) that a claimed mechanism of action was not understood by the prior art is not occurring and (2) that such newly discovered mode of action provides an unexpected advantage. In other words, when benzamil is administered topically or transdermally to a subject at a dosage that is optimized to treat claimed conditions, as is rendered obvious below, it is not clear that the inhibition of CXCL1 would not necessarily occur. Applicant should identify the active steps and limitations in the claims that distinguish and provide this particular result to the exclusion of that taught by the prior art.
Status of the Claims
Claims 1, 2, 4-9, and 11-18 are pending and examined.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 2, 4-7, 9, and 18 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Warren et al., (US2022/0062379) (filed January 17, 2020).
Warren teaches a method for treating immune dysregulation by administering a therapeutically effective amount of benzamil. See prior art claims 76 and 79. Further, the condition can be a dermatologic condition including eczema, dermatitis, vitiligo, and others. See prior art claim 83. Administration can be topically. See par. 39. Treatment can be a human or non-human. Further, administration can be systemic or local. See par. 40. As evidenced by the Specification, these conditions include those in which CXCL1 and TNFa are upregulated. For topical administration the dosage can be in the form of a cream, lotion, ointment, or gel. See par. 39.
Claims 76, 79, and 81-83 are shown below.
76. A method for treating a disease of immune dysregulation in a subject, said method comprising administering to the subject a therapeutically effective amount of a gliptin, benzamil, or ISA2011B.
79. The method of claim 76, wherein benzamil is administered.
81. The method of claim 76, wherein the disease of immune dysregulation is an inflammatory disease.
82. The method of claim 81, wherein the inflammatory disease is a dermatological disorder.
83. The method of claim 82, wherein the dermatological disorder is atopic dermatitis, alopecia areata, bulloid pemphigus, chronic eczema, dermatomyositis, erythema nodosum, epidermolysis bullosa, hydradenitis suppurativa, lichen planus, pemphigus vulgaris, psoriasis, pyoderma gangrenosum, scleroderma, or vitiligo.
As such, claims 1, 2, 4-7, 9, and 18 are anticipated by the prior art.
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, 2, 4-9, and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Warren et al., (US2022/0062379) (filed January 17, 2020).
Warren teaches a method for treating immune dysregulation by administering a therapeutically effective amount of benzamil. See prior art claims 76 and 79. Further, the condition can be a dermatologic condition including eczema, dermatitis, vitiligo, and others. See prior art claim 83. Administration can be topically. See par. 39. Treatment can be a human or non-human. Further, administration can be systemic or local. See par. 40. As evidenced by the Specification, these conditions include those in which CXCL1 and TNFa are upregulated.
Claims 76, 79, and 81-83 are shown below.
76. A method for treating a disease of immune dysregulation in a subject, said method comprising administering to the subject a therapeutically effective amount of a gliptin, benzamil, or ISA2011B.
79. The method of claim 76, wherein benzamil is administered.
81. The method of claim 76, wherein the disease of immune dysregulation is an inflammatory disease.
82. The method of claim 81, wherein the inflammatory disease is a dermatological disorder.
83. The method of claim 82, wherein the dermatological disorder is atopic dermatitis, alopecia areata, bulloid pemphigus, chronic eczema, dermatomyositis, erythema nodosum, epidermolysis bullosa, hydradenitis suppurativa, lichen planus, pemphigus vulgaris, psoriasis, pyoderma gangrenosum, scleroderma, or vitiligo.
With regard to claim 8, the examiner notes that an amount of a known result-effective variable would be optimized to achieve a desired therapeutic effect. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985); and generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
It would have been prima facie obvious to a person having ordinary skill in the art prior to the filing of the instant application to arrive at the claimed methods and products in view of the teachings of Warren. One would be motivated to optimize the concentration of a known result-effective variable through nothing more than routine experimentation and arrive at administering a dosage in a claimed form and route of administration that yields a claimed serum concentration. One can do so with a reasonable and predictable expectation of success.
As such, no claim is allowed.
Claims 1, 2, 4-9, 11, 14, 15, 17 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Warren et al., (US2022/0062379) (filed January 17, 2020), in view of Werther et al., (US2003/0096769).
Warren teaches a method for treating immune dysregulation by administering a therapeutically effective amount of benzamil. See prior art claims 76 and 79. Further, the condition can be a dermatologic condition including eczema, dermatitis, vitiligo, and others. See prior art claim 83. Administration can be topically. See par. 39. Treatment can be a human or non-human. Further, administration can be systemic or local. See par. 40. As evidenced by the Specification, these conditions include those in which CXCL1 and TNFa are upregulated.
Claims 76, 79, and 81-83 are shown below.
76. A method for treating a disease of immune dysregulation in a subject, said method comprising administering to the subject a therapeutically effective amount of a gliptin, benzamil, or ISA2011B.
79. The method of claim 76, wherein benzamil is administered.
81. The method of claim 76, wherein the disease of immune dysregulation is an inflammatory disease.
82. The method of claim 81, wherein the inflammatory disease is a dermatological disorder.
83. The method of claim 82, wherein the dermatological disorder is atopic dermatitis, alopecia areata, bulloid pemphigus, chronic eczema, dermatomyositis, erythema nodosum, epidermolysis bullosa, hydradenitis suppurativa, lichen planus, pemphigus vulgaris, psoriasis, pyoderma gangrenosum, scleroderma, or vitiligo.
Further, Warren teaches benzamil to provide substantial inhibition of TNF, IL6, and IL1β in a dose dependent manner. See Table 5, below.
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Werther teaches treating and preventing inflammatory skin disorders by administering an inhibitor of a one of the following: tumor necrosis factor alpha, IL-1, and IL-6 among a 9 total mediators. See prior art claims 1 and 2. Further, claim 5 provides that such method can treating specific conditions, including pityriasis rubra pilaris among a total of approximately 10 conditions.
With regard to claim 8, the examiner notes that an amount of a known result-effective variable would be optimized to achieve a desired therapeutic effect. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985); and generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
It would have been prima facie obvious to a person having ordinary skill in the art prior to the filing of the instant application to arrive at the claimed methods and products in view of the teachings of Warren and Werther. One would be motivated to optimize the concentration of a known result-effective variable through nothing more than routine experimentation and arrive at administering a dosage in a claimed form and route of administration that yields a claimed serum concentration. Further, Warren teaches benzamil is taught to be administered locally or systemically through topical, transdermal, and other routes of administration and is taught to dose-dependently inhibit tumor necrosis factor alpha, IL-1β, and IL-6 while Werther teaches that agents that accomplish inhibition of tumor necrosis factor alpha, IL-1, and IL-6 can be used to treat pityriasis rubra pilaris. As such, there is a reasonable and predictable expectation of success that a claimed agent will mitigate the form of inflammation known to be associated with the claimed condition thereby mitigating it.
Claims 1, 2, 4-9, 11-13, 16, and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Warren et al., (US2022/0062379) (filed January 17, 2020), in view of Kistowska et al., “IL-1b Drives Inflammatory Responses to Propionibacterium acnes In Vitro and In Vivo,” The Society for Investigative Dermatology 2014.
Warren teaches a method for treating immune dysregulation by administering a therapeutically effective amount of benzamil. See prior art claims 76 and 79. Further, the condition can be a dermatologic condition including eczema, dermatitis, vitiligo, and others. See prior art claim 83. Administration can be topically. See par. 39. Treatment can be a human or non-human. Further, administration can be systemic or local. See par. 40. As evidenced by the Specification, these conditions include those in which CXCL1 and TNFa are upregulated.
Claims 76, 79, and 81-83 are shown below.
76. A method for treating a disease of immune dysregulation in a subject, said method comprising administering to the subject a therapeutically effective amount of a gliptin, benzamil, or ISA2011B.
79. The method of claim 76, wherein benzamil is administered.
81. The method of claim 76, wherein the disease of immune dysregulation is an inflammatory disease.
82. The method of claim 81, wherein the inflammatory disease is a dermatological disorder.
83. The method of claim 82, wherein the dermatological disorder is atopic dermatitis, alopecia areata, bulloid pemphigus, chronic eczema, dermatomyositis, erythema nodosum, epidermolysis bullosa, hydradenitis suppurativa, lichen planus, pemphigus vulgaris, psoriasis, pyoderma gangrenosum, scleroderma, or vitiligo.
Further, Warren teaches benzamil to provide substantial inhibition of TNF, IL6, and IL1β in a dose dependent manner. See Table 5, below.
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Kistowska teaches: “In mice, inflammation induced by P. acnes is critically dependent on IL-1b and the NLRP3 inflammasome of myeloid cells. These findings show that the commensal P. acnes—by activating the inflammasome—can trigger an innate immune response in the skin, thus establishing the NLRP3-inflammasome and IL-1b as possible therapeutic targets in acne.” Abstract. Kistowska teaches that IL-1β is shown to be abundant in human acne lesions. See p678, 1st par. “Altogether, our data implicate IL-1β as a novel therapeutic target in acne.”
With regard to claim 8, the examiner notes that an amount of a known result-effective variable would be optimized to achieve a desired therapeutic effect. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985); and generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
It would have been prima facie obvious to a person having ordinary skill in the art prior to the filing of the instant application to arrive at the claimed methods and products in view of the teachings of Warren and Kistowska. One would be motivated to optimize the concentration of a known result-effective variable through nothing more than routine experimentation and arrive at administering a dosage in a claimed form and route of administration that yields a claimed serum concentration. Further, Warren teaches benzamil is taught to be administered locally or systemically through topical, transdermal, and other routes of administration and is taught to dose-dependently inhibit IL-1β while Kistowska teaches IL-1β to be a novel therapeutic target in the treatment of acne, which is shown to be abundant in human acne lesions. As such, there is a reasonable and predictable expectation of success that a claimed agent will mitigate the form of inflammation known to be associated with the claimed condition thereby mitigating it.
As such, no claim is allowed.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JARED D. BARSKY whose telephone number is (571)-272-2795. The examiner can normally be reached on Monday through Friday from 8:30 to 5:30. If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Amy L. Clark can be reached on 571-272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JARED BARSKY/Primary Examiner, Art Unit 1628
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