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 Claims
Claims 1-2, 5-7, 14, 19, 25, 27-30, 36-38, 44, 50, 52, 63, and 69 are pending as of the response and amendments filed on 12/29/25. Claims 3-4, 8-13, 15-18, 20-24, 26, 31-35, 39-43, 45-49, 51, 53-62, 64-68, and 70-71 have been canceled.
The rejection of claim 2 under 35 USC 112(b) is withdrawn in consideration of the amendments.
Claims 1-2, 5-7, 14, 19, 25, 27-30, 36-38, 44, 50, 52, 63, and 69 were previously rejected under 103 over Kohane, WO 2018053140. Applicants’ reasons for traversal are addressed below.
Applicants have argued Kohane doesn’t teach or suggest a composition of claim 1 as amended, and while poloxamer P188 is included in lists disclosed by Kohane, none of the compositions described in Kohane’s examples includes P188. Applicants have further argued only compositions comprising poloxamer P407 are included in Kohane’s examples, and Kohane disclosed “storage and loss moduli of the [3CPE-18%[P407]] formulation were less than 2 kPa over the temperature range of 20-40°C”, meaning the composition didn’t form a gel in the presence of 3CPE at 27 °C, the temperature at which the composition forms a gel in the absence of 3CPE.
Applicants’ arguments are not persuasive. The teachings of Kohane are not limited to disclosed examples, and as acknowledged by Applicants, poloxamer P188 is clearly taught by Kohane as a suitable polymer. See MPEP 2123 (II): Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). Furthermore, although the examiner acknowledges the example formulation referred to by Applicants, Kohane acknowledges the low cure rate in this example could be attributable to factors such as inadequate drug and/or CPE loading (see para [00272]). Kohane also clearly states “In certain embodiments, the sol-gel transition temperature of the composition is between about 20 °C and about 40 °C” (para [0021]), which overlaps with the claimed phase transition temperature range of less than about 37 °C.
Applicants have stated compositions of claim 1 as presently amended possess unexpected benefits that a POSITA would not have been able to predict based on Kohane’s disclosure. Applicants have pointed to p. 55, line 30-p. 56, line 5 of their specification in which it is described that a 45% [P188] solution forms a gel at 63 °C but the introduction of 3CPEs sharply decreased the gelation temperature as low as to 24 °C. Applicants have countered that in contrast, the 18% [P407] solution of Kohane with the 3CPEs increased the gelation temperature from 27 °C to 37 °C [para [0048]]. Applicants have additionally argued the addition of SDS, limonene, and/or bupivacaine to eight other poloxamers-P182, P331, P124, P401, P181, P231, P338, and pluronic 31R1 produced no compositions with the thermal-reversible gelation properties exhibited by P188.
Applicants’ arguments are not persuasive. As discussed previously, Kohane clearly teaches poloxamer P188 as well. Moreover, the example discussed by Applicants in their specification on p. 55, line 30-p. 56, line 5 is not commensurate in scope with the claims. Notably, this example evaluated poloxamer P188 at one concentration, 45%, while concentration of this polymer in the claims is considerably broader, from about 18% to about 62%. Additionally, this example requires all 3 CPEs, while the claims require only one of the CPEs in the composition; see claims 1-2. Regarding the evaluation of compositions incorporating other types of poloxamers P182, P331, P124, P401, P181, P231, P338, and pluronic 31R1, it is not evident from the specification whether the concentration of the poloxamers were the same as or differed from 45% P188. Unexpected results must be commensurate in scope with the claims; see MPEP 716.02(d): 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. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980). In the absence of unexpected results, the 103 rejection over Kohane is maintained.
Claims 1-2, 5-7, 14, 19, 25, 27-30, 36-38, 44, 50, 52, 63, and 69 were previously rejected for nonstatutory double patenting over the claims of US 8822410 B2, and 16333368 in view of Kohane. Applicants have provided similar reasoning in traversal of these double patenting rejections as to the traversal over the 103 rejection. Notably, Applicants have argued the claims of the ‘410 patent don’t teach or suggest the concentration ranges recited in claim 1 for SDS, bupivacaine, limonene, and/or poloxamer P188, or that the composition forms a gel above 37 °C, and that Kohane doesn’t cure these deficiencies.
Upon further consideration, the nonstatutory double patenting rejection over 16333368 is withdrawn. However, Applicants’ arguments pertaining to US 8822410 B2 are not persuasive. Notably, claim 10 of US ‘410 recites the composition to comprise 0.5% bupivacaine, about 2% limonene, and about 1% SDS, and claims 1-2 of this application as amended clearly include these CPEs in these concentrations. Additionally, claim 6 of US ‘410 includes poloxamer P188 as a matrix forming polymer in the composition. Kohane was cited in the rejection to teach the concentration of poloxamer P188 as recited in the claims, and the gelation temperature range. Therefore, the nonstatutory double patenting rejection over US ‘410 in view of Kohane is maintained.
Claims 1-2, 5-7, 14, 19, 25, 27-30, 36-38, 44, 50, 52, 63, and 69 were examined and are rejected.
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) 1-2, 5-7, 14, 19, 25, 27-30, 36-38, 44, 50, 52, 63, and 69 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kohane et. al., WO 2018053140 A1, publ. 3/22/2018, cited in an IDS.
Kohane teaches compositions comprising permeation enhancers and a matrix forming agent for delivery of a therapeutic agent across a biological barrier, wherein the matrix forming agent forms a gel at a suitable gelation temperature (title & abstract). In one particular embodiment, Kohane teaches the composition for the treatment of otitis media, wherein the composition is administered into the ear canal (para [0006], [0035]). Kohane teaches another embodiment wherein the composition has a gel transition temperature between about 0 °C and 37 °C (para [0011]). In a particular embodiment, the composition comprises: a) a therapeutic agent or combination of therapeutic agents; b) a permeation enhancer or combination of permeation enhancers; c) a matrix forming agent or combination of matrix forming agents comprising a polymer; wherein the sol-gel transition temperature is less than about 39 °C (para [0013]). The permeation enhancer or combination of permeation enhancers is present between about 0.1-30% by weight per volume of the composition, and the polymer is a block copolymer comprising a poloxamer, wherein the poloxamer is present between about 19-45% by weight per volume of the composition (para [0013]). Sodium dodecyl sulfate (SDS), limonene, and bupivacaine are all taught as permeation enhancers (para [0015], [0030-0031]), and Kohane provides an example formulation comprising 1% SDS, 2% limonene, and 0.5% bupivacaine (para [0048]). Poloxamer 188 is included as an exemplary polymer (para [0019], [0071], [00110], [00169]). Kohane teaches the therapeutic agent to be present between about 0.01-30% weight per volume of the composition (para [0033]), and teaches embodiments wherein the therapeutic agent includes a beta-lactam antibiotic or a fluoroquinolone antibiotic, such as ciprofloxacin, or another antibiotic such as ceftriaxone (para [0024], [00147], [00266]). Kohane teaches kits comprising a composition as described along with instructions for administering the composition to a subject in need thereof (para [0039], [00188-00191]).
It would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claims to have arrived at the composition of the instant claims comprising: a therapeutic agent or combination of therapeutic agents; a permeation enhancer selected from SDS, limonene, and/or bupivacaine, and a matrix forming polymer comprising poloxamer 188, wherein the composition forms a gel at a temperature less than about 37 °C in consideration of the teachings of Kohane. Kohane teaches compositions comprising the same components as recited in the instantly claimed composition, a therapeutic agent or combination of therapeutics; a permeation enhancer or combination thereof, along with explicit teaching of SDS, limonene, and bupivacaine as exemplary permeation enhancers in concentrations of 1%, 2%, and 0.5% by weight per volume of the composition respectively; and a matrix forming agent comprising a poloxamer between 19-45% by weight per volume of the composition, with poloxamer 188 exemplified. Kohane further teaches the concentration range of therapeutic between about 0.01-30%, permeation enhancer(s) SDS, limonene, and bupivacaine, and poloxamer that includes the ranges by weight per volume of the composition as recited in the claims, and exemplifies administering the composition, into the ear canal, for treating an ear disease such as otitis media. Additionally, Kohane teaches the composition to form a gel at a gel (sol-gel) transition temperature between about 0 °C and 39 °C. As such, one of ordinary skill in the art would have arrived at the composition of the instant claims by routine experimentation in consideration of the teachings of Kohane, and have treated an ear disease such as otitis media by administering the composition to the ear canal of a subject in need thereof, and have had a reasonable expectation of success.
Claim Rejections-Nonstatutory 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 1-2, 5-7, 14, 19, 25, 27-30, 36-38, 44, 50, 52, 63, and 69 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, and 6-11 of U.S. Patent No. 8822410 B2 in view of Kohane et. al., WO 2018053140 A1. Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are drawn to compositions comprising a therapeutic agent, a combination of penetration enhancers selected from bupivacaine, limonene, and SDS; and a matrix forming agent; and a method of treating comprising administering the composition. Both sets of claims recite poloxamer 188 as a matrix forming agent (see instant claim 1 & patented claim 6); wherein bupivacaine is present at 0.5%, limonene present at 2%, and SDS present at 1% in the composition (see patented claim 10 & instant claims 1-2). The amounts of bupivacaine, SDS, and limonene recited in the patented claim are included within the amount ranges recited by the instant claims (see instant claims 1-2, 7, 14, and 19). Additionally, both sets of claims recite the therapeutic agent as an antibiotic inclusive of ciprofloxacin or ceftriaxone (see patented claims 1 & 11 and instant claim 38). Although the patented claims don’t explicitly recite the amount of poloxamer 188, the amount of therapeutic, and the gel transition temperature as recited in the instant claims, these limitations would have been prima facie obvious in view of Kohane.
Kohane teaches compositions comprising permeation enhancers and a matrix forming agent for delivery of a therapeutic agent across a biological barrier, wherein the matrix forming agent forms a gel at a suitable gelation temperature (title & abstract). In one particular embodiment, Kohane teaches the composition for the treatment of otitis media, wherein the composition is administered into the ear canal (para [0006], [0035]). Kohane teaches another embodiment wherein the composition has a gel transition temperature between about 0 °C and 37 °C (para [0011]). In a particular embodiment, the composition comprises: a) a therapeutic agent or combination of therapeutic agents; b) a permeation enhancer or combination of permeation enhancers; c) a matrix forming agent or combination of matrix forming agents comprising a polymer; wherein the sol-gel transition temperature is less than about 39 °C (para [0013]). The permeation enhancer or combination of permeation enhancers is present between about 0.1-30% by weight per volume of the composition, and the polymer is a block copolymer comprising a poloxamer, wherein the poloxamer is present between about 19-45% by weight per volume of the composition (para [0013]). Sodium dodecyl sulfate (SDS), limonene, and bupivacaine are all taught as permeation enhancers (para [0015], [0030-0031]), and Kohane provides an example formulation comprising 1% SDS, 2% limonene, and 0.5% bupivacaine (para [0048]). Poloxamer 188 is included as an exemplary polymer (para [0019], [0071], [00110], [00169]). Kohane teaches the therapeutic agent to be present between about 0.01-30% weight per volume of the composition (para [0033]), and teaches embodiments wherein the therapeutic agent includes a beta-lactam antibiotic or a fluoroquinolone antibiotic, such as ciprofloxacin, or another antibiotic such as ceftriaxone (para [0024], [00147], [00266]). Kohane teaches kits comprising a composition as described along with instructions for administering the composition to a subject in need thereof (para [0039, [00188-00191]).
As such, it would have been prima facie obvious to modify the patented claims by incorporating poloxamer 188 into the composition between about 19-45% by weight per volume of the composition, which overlaps with the claimed range of between about 18-62%; and the therapeutic within the amount of about 0.01-30% by weight to volume of the composition, which overlaps with the claimed concentrations of antibiotic as recited by instant claim 44, in view of the guidance provided by Kohane. Additionally, as Kohane teaches the incorporation of a poloxamer such as poloxamer 188 into the composition, within the concentration range between about 19-45% by weight per volume of the composition results in a gel transition temperature of the composition of less than about 39 °C, incorporation of this polymer into the patented composition within the amount range would have resulted in the composition having a gel transition temperature of the composition of less than about 39 °C, which includes the claimed range.
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.
Information Disclosure Statement
The IDS filed on 12/29/25 has been considered.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARAH PIHONAK whose telephone number is (571)270-7710. The examiner can normally be reached Monday-Friday 9:00-5:30 EST.
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SARAH . PIHONAK
Primary Examiner
Art Unit 1627
/SARAH PIHONAK/Primary Examiner, Art Unit 1627