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 .
Oath/Declaration
Declaration filed under 37 C.F.R. 1.132 on 11/6/25 has been fully considered but is not found persuasive to overcome the obviousness conclusion of this case. See the discussion below in the Response to Arguments section.
Maintained Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 31, 38-40, 51-54 and 57-63 remain rejected under 35 U.S.C. 103 as being unpatentable over Chung et al. (US 2008/0107646; published: May 8, 2008; in IDS dated 12/21/23) in view of Day (US 20160045475; published: 2/18/16; of record), Fraser et al. (US 20150056276; published: Feb. 26, 2015; in IDS dated 12/21/23) and Fischer (US 2015/0150904; published: 6/4/15; of record).
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
Chung et al. is directed to method of ameliorating pruritus (Title). Chung et al. teach a method for preventing, treating or ameliorating pruritus caused by skin, mucosa or systemic disorder (e.g., psoriasis), wherein the method comprises administering to a subject with pruritus an effective amount of a formulation consisting essentially of a phenylbutyric acid or short-chain fatty acid derivative and a pharmaceutically acceptable carrier, salt or solvate thereof (limitation of instant claims 31, 57 and 60; Abstract and [0025]). Chung et al. teach that the other short chain fatty acid of 2-6 carbons in length include butyric acid and propionate (limitation of instant claims 31; [0020]).
Chung et al. teach wherein the formulation is formed into a capsule (claims; i.e., orally administered) or in the form of a topical gel applied to the affected skin six times per day for 1 week (limitation of instant claims 31, 57 and 60; [0039]).
Ascertainment of the Difference Between the Scope of the Prior Art and Claims
(MPEP §2141.012)
Chung et al. do not teach wherein the method also comprising administering a second pharmaceutical composition to the subject, wherein it comprises a therapeutically effective amount of a phosphodiesterase-4 (PDE4) inhibitor, such as apremilast ranging from 10 to 15 mg, as required by instant claims 31, 38-39, 57 and 60-61. However, such deficiency is cured by Day.
Day teaches that the PDE4 inhibitor, apremilast, is used to treat, prevent and/or manage psoriasis ([0002]). Day teaches that 10 mg of apremilast is a therapeutically-effect amount.
With regards to the amount of ingredients, Chung et al. do not teach specifically wherein the butyrate in the composition is from about 100 mg to 6 g and wherein the propionate is present in an amount of from about 25 mg to about 200 mg, as required by instant claims 52-53.
Furthermore, Chung et al. do not teach an embodiment wherein, for example, butyrate and propionate are combined in the same composition, as required by instant claims 31, 57 and 60.
Chung et al. do not teach wherein the composition further comprises a therapeutically effective amount of Vitamin D3 (from about 50 IU to about 200 IU), as required by instant claims 40, 54, 58-60 and 62. However, such deficiencies are cured by Fraser et al.
Fraser et al. is directed to compositions comprising omega-3 fatty acids and vitamin D for psoriasis (Title). Fraser et al. teach that a combination of Vitamin D and omega-3 fatty acids synergistically inhibit the proliferative/pro-inflammatory activity of key cells involved in the generation of psoriatic lesions (CD4+ T-cells and keratinocytes) ([0026]). And more specifically, Fraser et al. teach the incorporation of Vitamin D3 (see entire reference; e.g., claim 257) and wherein the total daily dosage of vitamin D may range in an amount from about 1000 to about 6000 IU.
Chung et al. do not teach wherein the first pharmaceutical composition further comprises a source of magnesium in an amount from about 10 to about 20 mg, as required by instant claims 31, 51, 57, 60 and 63. However, such deficiency is cured by Fischer.
Fischer is directed to a dietary supplement composition as a prophylactic and treatment for skin diseases such as psoriasis (Title). Fischer teaches that its composition comprises a phase II liver detoxification component having glycine and magnesium (Abstract). Fischer teaches that the magnesium is present in the orally administered composition in an amount of about 30 mg (which overlaps about 20 mg when you take into account +/- 10% for the term “about”). As indicated in MPEP §2144.05(I): “In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists.”
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
Based on these teachings, it would have been prima facie obvious to one of ordinary skill in the art, at the time the invention was made, to combine two compositions, each of which is taught by the prior art to be useful for the same purpose (short chain fatty acid of Chung et al. and apremilast (e.g., 10 mg) of Day for the purpose of treating psoriasis orally), in order to form a third composition to be used for the very same purpose (See MPEP 2144.06-I).
Regarding the concentration of butyrate, propionate and vitamin D3 as specified in claims 40 and 52-54, MPEP §2144.05 states:
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Furthermore, Chung et al. teach wherein the short-chain fatty acid derivative contains 2-6 carbons in length such as butyrate or propionate and is present in an amount ranging from about 0.00001 to about 100.00% by weight of the formulation (claims). More specifically, Chung et al. teach that the phenylbutyric acid derivative or short-chain acid active ingredient in a topical skin care composition is present in a dosage of 1 to 1000 mg, which overlaps with the claimed ranges (e.g., from about 100 mg to 6g, and from about 25 mg to about 200 mg of butyric and propionic acid, respectively) ([0023]; see MPEP §2144.05). Fraser et al. teach the incorporation of Vitamin D3 and wherein the total daily dosage of vitamin D may range in an amount from about 1000 to about 6000 IU. It is noted that this is the daily dose and a person of ordinary skill in the art would understand that human patients acquire some vitamin D3 from the environment (see [0022]) and their nutrition (for example, in fish and eggs). The Applicants' specification provides no evidence that the selected concentration range in claims 40 and 52-53 was not due to routine optimization and/or that the results should be considered unexpected compared to the prior art. Due to numerous factors (e.g., age, weight, sex, disease and stage of disease of patient, as well as patient’s baseline vitamin D3 amount), it would have been prima facie obvious to a person of ordinary skill in the art at the time of the invention to combine these teachings and alter the concentration. One of ordinary skill in the art would have been motivated to change the concentration as this could be expected to be advantageous for providing the optimal dose for the patient.
Based on these teachings, it would have been prima facie obvious to one of ordinary skill in the art, at the time the invention was filed, to combine two compositions, each of which is taught by the prior art to be useful for the same purpose (butyrate and propionate for the purpose of forming a composition effective in treating psoriasis (or symptoms thereof)), in order to form a third composition to be used for the very same purpose (See MPEP §2144.06-I).
The disclosures of Chung et al. and Fraser et al. are each directed to methods of treating pruritis (associated with psoriasis) and its symptoms by administering a composition (orally or topically). Therefore, it would have been prima facie obvious for a person of ordinary skill in the art to combine their respective teachings and to further incorporate vitamin D3 (and omega-e fatty acids) into the composition of Chung et al., as instantly claimed, with a reasonable expectation of success, at the time of the instant application. A person of ordinary skill would have been motivated to do so because Fraser et al. teach that vitamin D3-containing compositions help treat psoriasis.
Chung et al. and Fischer are both directed to methods of treating skin diseases such as psoriasis and its symptoms by administering a composition orally. Based on these teachings, it would have been prima facie obvious to one of ordinary skill in the art, at the time the invention was filed, to modify the composition of Chung et al. by further incorporating magnesium to achieve the predictable result of obtaining a composition suitable for treating psoriasis. One of ordinary skill in the art would have been motivated to do so because Fischer teaches that it is advantageous for phase II liver detoxification (Abstract). Fischer teaches that this phase 2 liver detoxification of salicylate in the patient enables patients suffering from skin diseases to eat a wider variety of foods without adverse effect.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Thus, the claimed invention was prima facie obvious before the effective filing date of the claimed invention.
Response to Arguments
Applicants’ arguments have been fully considered, but are not found persuasive.
Applicants argue that the Declaration (filed 11/6/25) provides data that the claimed combination therapy exhibits an unpredicted improvement in psoriasis-induced ear skin scaling in mice (See Fig. 1-6 in Declaration and p. 6-10 of the Remarks).
This is not found persuasive. In response to Applicants’ argument of unexpected results, the Examiner responds with the following statements:
(a) It is not clear from the test data provided in the specification that there is a synergistic effect across all tested concentrations. For example, in Figures 4-6, which shows the disease severity score at days 3, 4 and 5, respectively, the 12 mg/kg apremilast + fixed dose of SFA does not show a statistically different effect compared to either alone.
(b) Whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the “objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support.” In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range (see MPEP § 716.02(d)). In the instant case, the claims are directed to a method of treating psoriasis by orally administering a 1st pharmaceutical composition which comprises a therapeutically-effective amount of (i) butyric acid or a pharmaceutically acceptable salt thereof and (ii) propionic acid or a pharmaceutically acceptable salt thereof and (iii) a source of magnesium and administering a 2nd pharmaceutical composition which comprises a therapeutically effective amount of a PDE4 inhibitor. Different from the data provided in the Declaration, the claim is not narrowed to co-administration; it could be administration of 1st pharmaceutical composition one day and administration of 2nd pharmaceutical composition 28 days later. Also, the claimed “therapeutically effective amount” of all claimed ingredients could be a dose therapeutically effective when administered alone or in combination with any other ingredient including the claimed ingredients. However, the data presented in the Declaration is only wherein the fixed dose of SCFA includes 120 mg/kg/day of Ca-propionate, 1,100 mg/kg/day of the mixture of Ca-butyrate and Mg-butyrate and wherein the amount of PDE4 inhibitor was either 12 or 25 mg/kg. Furthermore, only one species of PED4 inhibitor was tested: apremiliast, whereas the independent claims can contain any known PDE4 inhibitor, even those not structurally similar or may not behave mechanistically the same (e.g., inhibit at a different site).
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 nonprovisional extension fee (37 CFR 1.17(a)) 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 GENEVIEVE S ALLEY whose telephone number is (571)270-1111. The examiner can normally be reached Monday-Friday 8:00-5:00.
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/GENEVIEVE S ALLEY/ Primary Examiner, Art Unit 1617