DETAILED ACTION
Previous Rejections
Applicant’s arguments, filed 03/03/2026, have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Claim Rejections - 35 USC § 103 - Obviousness
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 35-36, 37-38, 39-40, 43-53 and 55-57 are rejected under 35 U.S.C. 103 as being unpatentable over Macelloni et al (EP 3501496 A1), in view of Pedrani et al (US 2023/0181545 A1) and further in view of Moro et al (WO 2019/092614 A1).
Macelloni generally taught the treatment of inflammatory bowel disease [0154] in a patient [0007, 0208] comprising administering, by liquid enema [0040, 0204] or oral administration [claim 10, ¶s 0037, 0108, 0160], a pharmaceutical composition [0001, 0041] comprising an effective amount [0107], with therapeutic effect [0065, 0104], of rifamycin SV [0102] and a mixture of polymers [abstract]. The combination of polymers modulated the release of the active agent in situ [0049, 0053, 0166].
When administered, due to the superior flowability properties of the liquid composition therein disclosed, said composition automatically heated to body temperature (i.e. about 37°C), thus transitioning from liquid to a gel state (sol-gel transition) [0062].
The transition from a liquid form to a gel state enhanced the composition bio-adhesiveness, with a subsequent enhancement of their adhesion to the tissues, at the administration site for a suitable period of time, observed at physiological temperature (i.e. about 37°C) and at room temperature (i.e. about 25°C) of the composition [0064].
Macelloni generally taught the treatment of inflammatory bowel disease with rifamycin SV; however, was not specific treating ulcerative colitis and/or pouchitis, as recited in claim 35.
Nevertheless, Moro taught that the expression "inflammatory bowel disease", or IBD, indicates a series of chronic inflammatory intestinal pathologies, including, principally, ulcerative colitis [page 2, line 2], wherein pouchitis almost always occurs in patients with ulcerative colitis [page 7, 2nd ¶]. Moro taught pharmaceutical compositions containing rifamycin SV, for the treatment of pouchitis [abstract].
And, Pedrani indicated rifamycin SV for the treatment of ulcerative colitis [0002]. As per Pedrani, the currently available formulations (of rifamycin SV) are characterized by a frequency of administration (2-4 times a day) [0005].
Since Macelloni generally taught the treatment of inflammatory bowel disease with rifamycin SV, wherein inflammatory bowel disease includes ulcerative colitis, as taught by Moro, the ordinarily skilled artisan would have been motivated to treat ulcerative colitis, as taught by Pedrani. Furthermore, since pouchitis almost always occurs in patients with ulcerative colitis, as taught by Moro, the ordinarily skilled artisan would have, additionally, been motivated to treat, with rifamycin SV, pouchitis, as taught by Moro [Pedrani at ¶ 0002; Moro at [abstract, page 2 and line 2; and, page 7 at the 2nd paragraph].
Macelloni, in view of Pedrani and Moro, reads on claim 35-36 and 39-40.
Claims 37-38 are rendered prima facie obvious because Macelloni taught rectal administration, as previously discussed.
Regarding the instant claims 37-38, the claims recite alleviation of: clinical (claim 37), and endoscopy (claim 38) symptoms. The originally filed Specification disclosed that rectal administration of the pharmaceutical composition (e.g., rifamycin SV and a polymer mixture) alleviates clinical and endoscopic symptoms [0029, 0081].
It appears that the compositions (e.g., rifamycin SV and a polymer mixture) and methods (e.g., rectal administration) of the instant claims (e.g., rectal administration of a composition comprising rifamycin SV and a polymer mixture) and those of the prior art (e.g., rectal administration of a composition comprising rifamycin SV and a polymer mixture) would reasonably be expected to have substantially the same physical and chemical properties (e.g., alleviation of clinical and endoscopic symptoms).
Inherent features need not be recognized at the time of the invention. There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference. MPEP 2112 II. It should be noted that a chemical composition and its properties are inseparable. If the prior art teaches the identical chemical compounds (e.g., rectal administration of a composition comprising rifamycin SV and a polymer mixture), then the properties (e.g., alleviation of clinical and endoscopic symptoms) that the Applicant discloses and/or claims are necessarily present (see MPEP 2112).
The instant claims 39-40 recite administered daily (claim 39), or twice daily (claim 40).
Pedrani taught administration 2-4 times a day. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art", a prima facie case of obviousness exists. MPEP 2144.05 A.
Claims 42-44 are rendered prima facie obvious because Macelloni taught at least one thermo-responsive polymer (polymer A) (e.g., PEG-PLGA, poloxamer 124), at least one ion-sensitive polymer (polymer B) [abstract], and at least one bio-adhesive polymer (polymer C) [0011; see also ¶s 0069-0074]. Thermo-responsive polymers were taught at between about 0.1 % to about 30 % [0074-0075].
The instant claim 44 recites about 1 % to about 25 % thermos-responsive polymer.
Macelloni taught thermo-responsive polymers at between about 0.1 % to about 30 %. A prima facie case of obviousness exists because of overlap, as discussed above.
Claims 45-46 are rendered prima facie obvious because Macelloni taught ion-sensitive polymers (e.g., pectin, alginic acid) in an amount of about 0.1% or about 0.2 % or about 0.3% or about 0.5% or about 1% or about 2% by weight [0076-0078]. Sodium alginate was taught at Examples 1, 3-6, 8 and 10-13.
The instant claim 46 recites about 0.01 % to about 3 % ion-sensitive polymer. Macelloni taught ion-sensitive polymers in an amount of about 0.1% or about 0.2 % or about 0.3% or about 0.5% or about 1% or about 2% by weight. A prima facie case of obviousness exists because of overlap, as previously discussed.
Claims 47-48 are rendered prima facie obvious because Macelloni taught bio-adhesive polymers (e.g., chitosan, hyaluronic acid, methyl cellulose, sodium carboxymethylcellulose) [0090-0095]. At Examples 5-7, sodium carboxymethylcellulose was taught at 0.100 %.
The instant claim 48 recites about 0.01 % to about 2 % bio-adhesive polymer. Macelloni taught a bioadhesive polymer at 0.100 %. A prima facie case of obviousness exists because of overlap, as previously discussed.
Claim 49 is rendered prima facie obvious because Macelloni taught antioxidants [0203]. The pH was taught at ranging from about 4.0 to about 10.0 [0183].
The instant claim 49 recites a pH of 6.5 to 7.5. Macelloni taught a pH ranging from about 4.0 to about 10.0. A prima facie case of obviousness exists because of overlap, as previously discussed.
Claim 50 is rendered prima facie obvious because Macelloni taught 0.060 % (e.g., about 0.1 %) rifamycin sv [Example 11].
The instant claim 50-51 recite from about 0.1 to about 5 % Rifamycin SV. Macelloni taught 0.060 % (e.g., about 0.1 %) rifamycin sv. A prima facie case of obviousness exists because of overlap, as previously discussed.
Claims 51-53 are rendered prima facie obvious over Macelloni, because Macelloni taught 0.060 % (e.g., about 0.1 %) rifamycin sv; thermo-responsive polymers were taught at between about 0.1 % to about 30 % [previously discussed]; ion-sensitive polymers in an amount of about 0.1% or about 0.2 % or about 0.3% or about 0.5% or about 1% or about 2% by weight [previously discussed]; bioadhesive polymers at 0.100 % [previously discussed].
The instant claim 51 recites from about 0.1 to about 5 % Rifamycin SV; thermos-responsive polymer at from about 1 % to about 25 %; ion-sensitive polymer at from about 0.01 % to about 3 %; bio-adhesive polymer at from about 0.01 % to about 2.0 %.
The instant claim 52 recites from about 0.1 to about 5 % Rifamycin SV; thermos-responsive polymer at from about 12 % to about 18 %; ion-sensitive polymer at from about 0.1 % to about 2 %; bio-adhesive polymer at from about 0.05 % to about 0.1 %.
The instant claim 53 recites from about 0.25 to about 2.5 % Rifamycin SV; thermos-responsive polymer at from about 12 % to about 18 %; ion-sensitive polymer at from about 0.1 % to about 2.0 %; bio-adhesive polymer at from about 0.05 % to about 0.1 %.
Macelloni taught 0.060 % (e.g., about 0.1 %) rifamycin sv; thermo-responsive polymers were taught at between about 0.1 % to about 30 %; ion-sensitive polymers in an amount of about 0.1% or about 0.2 % or about 0.3% or about 0.5% or about 1% or about 2% by weight; bioadhesive polymers at 0.100 %. A prima facie case of obviousness exists because of overlap, as discussed above.
As to claim 53, the claim requires from about 0.25 to about 2.5 % Rifamycin SV. Macelloni taught 0.060 % (e.g., about 0.1 %) rifamycin sv. It is noted that no surprising effect has been provided in the present application coming from the claimed specific regimen, if compared with the dosage of the combined teachings of Macelloni, in view of Pedrani and Moro. It is considered that in the absence of any effect linked to such a feature over those known from the prior art, the single structural modification such as variation of dosage regimen belongs to common experimental design, that a skilled person, who is aware that for the effective treatment of inflammatory bowel disease, ulcerative colitis and pouchitis, rifamycin SV is required, would optimize in routine experiments. In the absence of evidence (experimental comparative data) in the present application showing that the specific dosage regimen possesses an unexpected, surprising effect compared to the regimen known in the prior art, no inventive step can be acknowledged. Where 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. See MPEP 2144.05(II)(A).
In this case, the general conditions of administration of rifamycin SV by rectal administration to treat inflammatory bowel disease, ulcerative colitis and pouchitis, have been taught by the combined teachings of the prior art; as such, it would not have been inventive for the skilled artisan to have discovered the optimum dosage of rifamycin SV via routine experimentation.
Claims 55-57 are rendered prima facie obvious because Macelloni taught hydroxypropyl methylcellulose [claim 2] and sodium alginate [0011].
Response to Arguments
Applicant's arguments filed 03/03/2026 have been fully considered but they are not persuasive.
Applicant argued that Macelloni was read to provide the elements of the Applicant’s claims by the Examiner with improper hindsight reasoning.
The Examiner disagrees, and responds that it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the Applicant's disclosure, then such a reconstruction is proper. See MPEP 2145. In the instant case, Macelloni generally taught treating inflammatory bowel disease by liquid enema administration of rifamycin SV, wherein said administration comprised a combination of polymers that released the active in situ [see the nonfinal office action].
Applicant argued that Macelloni taught a number of active substances, to treat a number of diseases. Applicant cited Macelloni at the abstract, in support of the alleged conclusion that Macelloni was not specific treating inflammatory bowel disease with rifamycin SV; liquid enema or rectal administration. Applicant cited Macelloni at ¶ [0120] to argue that rifamycin SV was provided in a list of antimicrobics or antibiotics. Applicant cited Macelloni at ¶s [0045 and 0154] to argue that inflammatory bowel disease is one of many pathologies affecting the gastrointestinal tract.
The Examiner is not persuaded by this argument, because the list [0120] of antimicrobics or antibiotics is at most three lines long. The list [0154] of inflammatory bowel diseases is at most fourteen lines long. These lists present “a finite number of identified, predictable solutions,” expressly including at least one combination of rifamycin SV and inflammatory bowel disease. The Applicant fails to provide a persuasive reason why it would not have been within the skill of the ordinarily skilled artisan, to try the limited number of actives and diseases, in order to arrive, in combination with the cited prior art, at the claimed method for treating, via rectal administration.
Applicant argued that Macelloni’s Example 11 provides that rifamycin SV may be applied via injection for the treatment of fistulas; however, this route and disease are not presently claimed.
The Examiner responds that Macelloni’s Example 11 was not relied upon in the rejection of the claims.
Applicant argued that Macelloni does not explicitly teach rectally administering rifamycin, nor does it specifically teach administering rifamycin via liquid enema.
The Examiner disagrees. Macelloni taught rifamycin, as discussed above, and as discussed in the body of the rejection. See Macelloni’s teachings at ¶ [0120]. As discussed in the body of the rejection, and at ¶ [0040], Macelloni taught “the liquid composition of the invention can be in form of enema”.
Applicant argued that Moro and Pedrani taught oral formulations, and that neither Moro nor Pedrani taught treating pouchitis, proctitis and/or distal ulcerative colitis by rectal administration of rifamycin SV.
The Examiner reminds the Applicant that one cannot show nonobviousness by attacking references individually, where the rejection was based on a combination of references. See MPEP 2145(IV). In the instant case, Macelloni taught rectal administration of rifamycin SV, in the treatment of inflammatory bowel disease; Moro taught that pouchitis occurs in ulcerative colitis patients, where inflammatory bowel disease includes ulcerative colitis; and, Pedrani taught rifamycin SV for the treatment of ulcerative colitis [see the outstanding rejection].
Claim(s) 41 is rejected under 35 U.S.C. 103 as being unpatentable over Macelloni et al (EP 3501496 A1), in view of Pedrani et al (US 2023/0181545 A1), further in view of Moro et al (WO 2019/092614 A1) and further in view of Yamada et al (US 2018/0271786 A1).
The 35 U.S.C. 103 rejection over Macelloni, Pedrani and Moro was previously discussed.
Although Macelloni taught rectal administration, Macelloni did not teach rectal administration for at least two weeks, as recited in claim 41.
Yamada taught a liquid shape enema for rectal application containing an active ingredient to treat inflammatory bowel disease, or to prevent a relapse. The enema for rectal administration was administered over two weeks, and not more than six weeks, in order to obtain a sufficient effect [abstract, ¶ 0030].
Since Macelloni generally taught the treatment of inflammatory bowel disease by rectal enema, it would have been prima facie obvious to one of ordinary skill in the art to include, within the combined teachings of the prior art, administration over two to six weeks, as taught by Yamada. The ordinarily skilled artisan would have been motivated to obtain a sufficient effect, as taught by Yamada [abstract, ¶ 0030].
Response to Arguments
Applicant's arguments filed 03/03/2026 have been fully considered but they are not persuasive.
Applicant argued that Yamada does not cure the deficiencies of Macelloni, Pedrani and Moro.
The Examiner disagrees. Macelloni, Pedrani and Moro are not deficient, except where Moro taught administration for at least two weeks.
Claim 54 is rejected under 35 U.S.C. 103 as being unpatentable over Macelloni et al (EP 3501496 A1), in view of Pedrani et al (US 2023/0181545 A1),further in view of Moro et al (WO 2019/092614 A1) and further in view of Monteleone et al (US 2018/0180630 A1).
The 35 U.S.C. 103 rejection over Macelloni, Pedrani and Moro was previously discussed.
Macelloni generally taught the treatment of inflammatory bowel disease with rifamycin SV, however was not specific a patient suffering from proctosigmoiditis, as recited in claim 54.
Nevertheless, Monteleone taught that the category of “inflammatory bowel disease” refers to a number of chronic inflammatory disease including proctosigmoiditis [0366].
It would have been prima facie obvious to one of ordinary skill in the art to include, within the teachings of Macelloni, proctosigmoiditis, as taught by Monteleone. The ordinarily skilled artisan would have been so motivated, because “inflammatory bowel disease” refers to a number of chronic inflammatory disease including proctosigmoiditis, as taught by Monteleone [0366].
Response to Arguments
Claim 54 is newly applied, and has not been traversed.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
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/CELESTE A RONEY/ Primary Examiner, Art Unit 1612
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