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 Amendment
The Amendment filed 04/01/2026 has been entered. Applicant’s amendments are in response to in the Non-Final Office Action mailed 10/06/2025. Applicant’s claims have been amended in the following manner: independent claim 1 has been significantly modified by narrowing the poloxamer selection to P188 (i.e., limitation moved from now-cancelled claim 4), and by emphasizing a sustained plasma concentration in the “wherein” clause. Note that independent claim 1 (and amendments incorporated to claim 1) is read as a composition claim (per the restriction requirement filed 01/13/2025), and thus, the “wherein” clause is regarded as an intended result of the composition (providing no patentable weight because it does not provide structure to the composition) and furthermore, the “certain periods of time” phrase is not limited to a specific number, period, or range of time. Furthermore, claim 2 adds a second surface modifier (supported by Applicant’s Specification at [0078]) . Finally, claims 19-21 are newly introduced with additional surface modifiers (supported by Applicant’s Specification at [0079-0080]).
The amendments made to the claim set have a prompted a new ground of rejection, that shifts the previous 102 rejection (over Andries) to the current 103 rejection, and also modifies the 103 rejection (over Hemelryck). The Examiner concedes the error regarding the trademark name for poloxamer 188 (or P188) of the previous action (with regard to the Andries rejection, as argued in Applicant’s remarks), but notes that Andries still teaches the obviousness of the amended claim scope, within the context of a 103 rejection (because Andries teaches suitable surface modifiers such as “Pluronic™ F68, F108 and F127 which are block copolymers of ethylene oxide and propylene oxide” (pg 20, bottom paragraph), whereby Pluronic F68 corresponds to poloxamer 188).
The following objections/rejections are withdrawn: 112b rejections (on the basis of amendments made with regard to “about” and the broad and narrow ranges, except for claim 16), and the Specification Objection (in the newly filed Specification, the Examiner notes the proper ordering/format of the Specification pages).
The Examiner further acknowledges the following:
Claims 1-3, 5-14, and 16-21 are pending.
Claims 8-14 and 18 are withdrawn from consideration as directed to non-elected inventions.
Claims 1-3, 5-7, 16-17, and 19-21 are presented for examination and rejected as set forth below.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 16 and 21 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 16 recites the term “about”, where “about” represents many numerical ranges in the Specification such as +10%, or +5%, or +2%, or +1% [00109], and is therefore still indefinite, when written as “below about 200 nm +10%). Regarding the indefiniteness of broad and narrow ranges, see MPEP § 2173.05(c).
Claim 21 (new) recites Trademark names (i.e., Tween™ 80, and Lipoid™ EPG). The claim scope is uncertain since the trademark or trade name cannot be used properly to describe any particular material or product. In fact, the value of a trademark would be lost to the extent that it became the generic name of a product, rather than used as an identification of a source or origin of a product. Thus, the use of a trademark or trade name in a claim to describe a material or product would not only render a claim indefinite, but would also constitute an improper use of the trademark or trade name." (MPEP 2173.05(u)). The Examiner suggests substitution of the generic name of the ingredients, representing the trademark names.
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.
Claims 1-3, 5-7, 16-17, and 19-21 are rejected under 35 U.S.C. 103 as being unpatentable over Andries (WO2019012100A1; cited on the IDS filed 03/09/2023; published 01/17/2019, which is outside the 1-year grace period of the foreign application filing date 07/09/2020).
Applicant’s claims are directed an intramuscular or subcutaneous injection composition comprising bedaquiline in micro- or nanoparticle form, a poloxamer (i.e., P188, aka poloxamer 188 or tradename Pluronic™ F68), and an aqueous carrier, wherein sustained plasma concentration of bedaquiline and/or its metabolites are seen over time. Note that amounts in claims 7 and 17, where the ranges reach 0% are considered optional to the composition.
Andries discloses a pharmaceutical composition for administration via intramuscular or subcutaneous injection comprising bedaquiline (pg 1, field of invention). Furthermore, the surface modifiers of this disclosure adsorb onto drug substance surface’s to achieve long-acting formulations (pg 2, paragraph 3). Andries teaches this approach leads to sufficient plasma levels of bedaquiline at time intervals of one week or longer to provide prevention against transmission of mycobacterial infection (pg 3, paragraph 2).
Regarding claims 1, 3 and 19: Andries teaches a pharmaceutical composition for administration by intramuscular or subcutaneous injection, comprising a therapeutically effective amount of bedaquiline, or a pharmaceutically acceptable salt thereof, in the form of a suspension of micro- or nanoparticles comprising: bedaquiline, a surface modifier that can be a poloxamer, and a pharmaceutically acceptable aqueous carrier (Andries – claims 1 and 2). Andries teaches bedaquiline is in its non-salt or free form or in the form of a fumarate salt (Andries – claim 3).
Andries teaches suitable surface modifiers such as “Pluronic™ F68, F108 and F127 which are block copolymers of ethylene oxide and propylene oxide” (pg 20, bottom paragraph), whereby Pluronic F68 corresponds to poloxamer 188.
Regarding claim 2: Andries teaches the obviousness of adding a second surface modifier by stating “if desired, two or more surface modifiers can be used in combination” (reads on instant claim 2) (pg 21, paragraph 1).
Regarding claims 5-6 and 16: Andries teaches the average effective particle size of the bedaquiline, or a pharmaceutically acceptable salt thereof, micro- or nanoparticles is below about 50 um or about 130 nm (reads on below 50 um, 130 nm, and below 200 nm) (Andries – claims 5 and 6).
Regarding claims 7 and 17: Andries teaches the same weight-based ranges for the composition (see amounts specifically in, Andries – claim 7).
Because the Andries WIPO reference obeys international claiming conventions, the instantly claimed amounts (and also particle sizes) are “at once envisaged” because the tightest instant ranges reside within the broadest ranges of the primary reference.
Regarding claim 20: Andries teaches surface modifiers such as a-tocopheryl polyethylene glycol succinates, polyoxyethylene sorbitan fatty acid esters, and salts of negatively charged phospholipids or the acid form thereof (Andries – claim 2; pg 21, paragraph 2).
Regarding claim 21: Andries teaches incorporation of Vitamin E TGPS, Tween™ 80, and Lipoid™ EPG (Andries – claim 4).
Thus, the instant composition is obvious based on the single reference providing the elements and motivation to make the instant composition.
Claims 1-3 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Hemelryck (Int. J. of Pharm., 2019).
Hemelryck discloses a pharmaceutical composition for administration via intramuscular or subcutaneous injection comprising bedaquiline (abstract).
Regarding claims 1-3 and 19: Hemelryck teaches the desirability of using poloxamers (i.e., P188 and P338) for their low cost, low toxicity, high water solubility, and their many functions, including to make in situ forming gels that affect in vitro and in vivo drug release (pg 2, left column). Hemelryck teaches a pharmaceutical composition comprising bedaquiline fumarate salt, also discussing free base equivalents (reads on instant claims 1(a), 3 and 19) (pg 2, paragraph 4) and poloxamer 338 and/or 407 (reads on claim 2) (Table 3 demonstrates the obviousness of multiple surface modifiers) in NMP/water mixtures (reads on 1(b)) for injection and sustained-release action (abstract). Hemelryck also teaches long acting injectables comprising the categories of micro- or nanosuspensions and in situ forming gels (pg 2, paragraph 1), thus, providing motivation to develop a suspension formulation with micro- or nanoparticles. Hemelryck demonstrates sustained release of the intramuscular injection formulation, showing bedaquiline levels in plasma over time (pg 7, Figure 4).
Thus, the instant composition is obvious based on the single reference providing the elements and motivation to make the instant composition.
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 1-3, 5-7, 16-17, and 19-21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over, and in further view of Andries (WO2019012100A1; cited on the IDS filed 03/09/2023):
claims 1, 5-10, and 16-19 of copending Application No. 18/004,464 (reference application)
claims 1-17, and 38-41 of copending Application No. 18/004,336 (reference application)
Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets teach a suspension composition comprising bedaquiline in micro- or nanoparticle form, a surface modifier, and an aqueous carrier. The copending applications differ only significantly by not including poloxamer as the selected surface modifier.
This is remedied by Andries, who teaches poloxamers for incorporation into the composition as surface modifiers (Andries – claims 1 and 2), including one or more additional surface modifiers from another class of molecules (see 103 rejection above). Furthermore, Andries teaches the obviousness of Pluronic F68 (corresponds to poloxamer 188) (pg 20, bottom paragraph), and adding a second poloxamer: “if desired, two or more surface modifiers can be used in combination” (pg 21, paragraph 1).
One of ordinary skill in the art would have been motivated to modify the teachings of the copending applications by substituting the copending surface modifiers with the poloxamer described by Andries, because the applications are directed toward long-acting injectable bedaquiline suspension compositions and the poloxamers are stated to function as surface modifiers.
This is a provisional nonstatutory double patenting rejection.
Claims 1-3, 5-7, 16-17, and 19-21 are rejected on the ground of statutory double patenting as being unpatentable over Claims 1-8 of Patent 11141384 (same patent family as WO2019012100A1 used in the 103 above), and in further view of Andries (WO2019012100A1).
Both claim sets teach a suspension composition comprising bedaquiline in micro- or nanoparticle form, a surface modifier (poloxamer), and an aqueous carrier in the instant amounts.
Furthermore, Andries teaches the obviousness of Pluronic F68 (corresponds to poloxamer 188) (pg 20, bottom paragraph), and adding a second poloxamer: “if desired, two or more surface modifiers can be used in combination” (pg 21, paragraph 1).
Claims 1-3, 5-7, 16-17, and 19-21 are rejected on the ground of statutory double patenting as being unpatentable over Claims 1-19 of Patent 12171887 (same patent family as WO2019012100A1 used in the 103 above), and in further view of Andries (WO2019012100A1).
Both claim sets teach a suspension composition comprising bedaquiline in micro- or nanoparticle form, a surface modifier (poloxamer), and an aqueous carrier in the instant amounts.
Furthermore, Andries teaches the obviousness of Pluronic F68 (corresponds to poloxamer 188) (pg 20, bottom paragraph), and adding a second poloxamer: “if desired, two or more surface modifiers can be used in combination” (pg 21, paragraph 1).
Response to Arguments
Applicants arguments, see pg 7-10, filed 04/01/2026, with respect to the 102 rejection (over Andries) of claims 1-7 and 15-17 under rejection have been fully considered and are persuasive. Therefore, the 102 rejection has been withdrawn. However, upon further consideration and in view of applicant’s amendments to the claims, a new ground of rejection is made in the form of the 103 rejection above.
Applicants arguments, see pg 7-10, filed 04/01/2026, with respect to the 103 rejection (over Hemelryck) of claims 1-4 and 15 have been fully considered but they are not persuasive. The 103 rejection has been modified with respect to amendments made to the claim set and new added claims. Applicant’s arguments against Hemelryck are not persuasive.
On page 7-8, Applicant argues that Pluronic F108 corresponds to poloxamer 338. The Examiner concedes this point, and notes the error of the previous Office Action. However, it does not negate the larger teaching of Andries in the context of an obviousness rejection (which effectively adapts the 102 rejection to a 103 rejection, in conjunction with Applicant’s amendments in the current amendment), when Andries teaches suitable surface modifiers suitable for long-acting bedaquiline formulations, such as “Pluronic™ F68, F108 and F127 which are block copolymers of ethylene oxide and propylene oxide” (pg 20, bottom paragraph). Applicant discusses that Pluronic F-68 is the trade name for poloxamer 188, thus, based on this evidence, and the teachings of Andries, the instant claim 1 limitation that incorporates poloxamer 188 is prima facie obvious per Andries. Additionally, the other amendments made to the claim set are addressed in the 103 rejection above (over Andries).
On page 8-9, Applicant argues that Hemelryck’s teaching would not lead a PHOSITA to use poloxamer 188 to compose a gel formulation of bedaquiline. Hemelryck does not teach away from using P188. In order to teach away from a proposed modification, the art must “criticize, discredit, or otherwise discourage the solution claimed….” In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004). The art does not criticize, discredit, or otherwise discourage the modification proposed by the Examiner. Applicant’s arguments center around P188 properties in general, and that P407 is better than P338, which is not convincing discourse to teach away from P188. There is no objective data to support a position of teaching away from P188, but only speculation/argument.
Additionally, inferior embodiments are still obvious (i.e., Applicant suggests the properties of P188 may lead to an inferior formulation): An obvious composition suggested as inferior does not afford patentability: In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). “A known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use.” Although there is no evidence that a P188 formulation would be inferior, it is still an obvious formulation within the context of Hemelryck.
Furthermore, Hemelryck teaches poloxamer in situ forming gels (title, abstract), and merely lacks an exemplary embodiment using poloxamer P188. Hemelryck teaches poloxamers of “commonly used grades include P188, P237, P338 and P407” for long-acting formulations (pg 100016, paragraphs 1-3). Thus, a PHOSITA would see Hemelryck’s formulations of Table 3 that incorporate P338 and P407 and would consider it obvious to use P188 in a formulation, because “Art is art, not only for what it expressly teaches, but also for what it would reasonably suggest to the skilled artisan, including alternative or non-preferred embodiments. Merck & Co. v. Biocraft Laboratories, 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989).” As said before, Hemelryck does not criticize the use of P188 in long-acting formulations.
With regard to the reasonable expectation of success of incorporating P188 for long-acting bedaquiline injections: “Applicants are reminded that obviousness does not require absolute predictability. See In re Rinehart, 531 F.2d 1048, 189 USPQ 143 (CCPA 1976) (indicating that evidence showing there was no reasonable expectation of success may support a conclusion of nonobviousness).” Furthermore, Applicant has not provided evidence that unpredictability of the art to challenge the obviousness of the modification, whereby Hemelryck considers P188 as a “commonly used grade” of poloxamer (pg 100016, paragraphs 1-3).
On pages 9-10, Applicant addresses the double patenting (to be held in abeyance) and concludes. No further action is needed here.
Correspondence
Applicant's amendment necessitated the new ground 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 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RAJAN PRAGANI whose telephone number is (703)756-5319. The examiner can normally be reached 7a-5p EST (M-Th).
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, Ali Soroush can be reached on 571-272-9925. 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.
/R.P./Examiner, Art Unit 1614 4/30/2026
/SEAN M BASQUILL/Primary Examiner, Art Unit 1614
Prosecution Insights