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 .
Election/Restrictions
Applicant's election with traverse of Group I, claims 1-7 and 27-28 in the reply filed on 11/17/2025 is acknowledged. The traversal is on the ground(s) that the claims pending in the application have unity since they are drawn to product, a process specially adapted for the manufacture of the said product, and a use of the said product, therefore Applicant requests that claims 8-17, 27-28 be examined together in this application. This is not found persuasive because there is both a search and examination burden for each group.
The requirement is still deemed proper and is therefore made FINAL.
Claims 8-17 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected Groups II and III, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 11/17/2025.
Status of the Claims
Claims 18-26 and 29-37 have been cancelled. Claims 1-17 and 27-28 are pending. Claims 8-17 have been withdrawn.
Claims 1-7 and 27-28 are currently under examination.
Information Disclosure Statement
Initialed and dated copies of Applicants’ information disclosure statements (IDS) filed on 03/09/2023, 04/14/2023, 12/04/2023, 03/25/2024, 09/18/2024, 03/31/2025, 07/24/2025, 08/20/2025, 09/05/2025, and 10/13/2025 are attached to the instant Office action. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
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 1-7 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.
The term “high” in claim 1, line 4, is a relative term which renders the claim indefinite. The term “high” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The examiner points out that Merriam-Webster dictionary defines the term “high” as of greater degree, amount, cost, value, or content than average, usual, or expected.
The term “high” in claim 2, line 2, is a relative term which renders the claim indefinite. The term “high” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The examiner points out that Merriam-Webster dictionary defines the term “high” as of greater degree, amount, cost, value, or content than average, usual, or expected.
Regarding claim 7, the phrase "i.e." on line 7 renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 7, the phrase "or the like" renders the claim(s) indefinite because the claim(s) include(s) elements not actually disclosed (those encompassed by "or the like"), thereby rendering the scope of the claim(s) unascertainable. See MPEP § 2173.05(d).
Claims depending from rejected claims have also been rejected because they incorporate
all of the limitations of the claims from which they depend, but fail to resolve the indefiniteness
concerns outlined above.
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.
Claims 1-7 and 27 are rejected under 35 U.S.C. 103 as being unpatentable over Andries et al. (WO2019012100A1, Published 01/17/2019; cited in the IDS filed 03/09/2023).
Applicant’s Invention
Applicants’ claims are drawn to a pharmaceutical composition for administration by intramuscular or subcutaneous injection, comprising: (a) a therapeutically effective amount of bedaquiline, or a pharmaceutically acceptable salt thereof, in micro- or nanoparticle form, and a surface modifier comprising a high-molecular weight polyethylene glycol; and (b) a pharmaceutically acceptable aqueous carrier.
Determination of the scope and the content of the prior art
(MPEP §2141.01)
Regarding claim 1, Andries teaches the present invention is concerned with 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: (a) bedaquiline, or a pharmaceutically acceptable salt thereof, in micro- or nanoparticle form, and a surface modifier; and (b) a pharmaceutically acceptable aqueous carrier (page 3, lines 13-20). Andries further teach that suitable surface modifiers can be selected from polyethylene glycols (such as Carbowax 3550) (i.e., high molecular weight polyethylene glycol) (page 21, line 7).
Regarding claims 2 and 27, Andries teaches that suitable surface modifiers can be selected from polyethylene glycols (such as Carbowax 3550) (i.e., high molecular weight polyethylene glycol) (page 21, line 7). Andries further teaches if desired, two or more surface modifiers can be used in combination (page 21, lines 11-12).
Regarding claims 3 and 4, Andries teaches Particular surface modifiers are selected from poloxamers, a-tocopheryl polyethylene glycol succinates, polyoxyethylene sorbitan fatty acid esters, and salts of negatively charged phospholipids or the acid form thereof (page 21, lines 14-16).
Regarding claim 5, Andries teaches Bedaquiline can be used in its non-salt form or as a suitable pharmaceutically acceptable salt form, such as an acid addition salt form or base addition salt form (page 8, lines 5-7). Andries further teaches in particular, the fumarate salt is considered as the salt form which bedaquiline is able to form (page 8, lines 18-19).
Regarding claim 6, Andries teaches the pharmaceutical compositions of the invention comprise bedaquiline in nanoparticle form. The average effective particle size of the micro- or nanoparticles of the present invention may be below about 50 μm (pages 9-10, lines 35-37; lines 1-2).
Regarding claim 7, Andries teaches In one embodiment, the aqueous suspensions may comprise by weight, based on the total volume of the composition: (a) from 10% to 70% (w/v), or from 20% to 60% (w/v), or from 20% to 50% (w/v), or from 20% to 40% (w/v) of bedaquiline (or pharmaceutically acceptable salt thereof); (b) from 0.5% to 20 %, or from 2% to 15% or 20% (w/v), or from 5% to 15% (w/v) of a wetting agent; (c) from 0% to 10%, or from 0% to 5%, or from 0% to 2%, or from 0% to 1% of one or more buffering agents; (d) from 0% to 20 %, or from 2% to 15% or 20% (w/v), or from 5% to 15% (w/v) of a isotonizing agent (e) from 0% to 2% (w/v) preservatives; and (f) water for injection q.s. ad 100% (pages 25-26, lines 27-37; lines 1-2).
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
Andries does not disclose a single embodiment or example where every limitation recited in the instant claims is taught.
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
The claims are considered prima facie obvious to one of ordinary skill in the art before the time of filing because Andries teaches all of the claimed elements. It would have been prima facie obvious to one of ordinary skill in the art before the time of filing to make a pharmaceutical composition for administration by intramuscular or subcutaneous injection, comprising: (a) a therapeutically effective amount of bedaquiline, or a pharmaceutically acceptable salt thereof, in micro- or nanoparticle form, and a surface modifier comprising a high-molecular weight polyethylene glycol; and (b) a pharmaceutically acceptable aqueous carrier because Andries teaches and contemplates all the elements required to make the pharmaceutical composition.
With regards to claim 2, wherein the surface modifier comprises at least 75% by weight of the high-molecular weight polyethylene glycol and the remainder is one or more other suitable surface modifiers, it would have been obvious to one of ordinary skill in the art to vary the amounts of each surface modifier to achieve the desired concentration of the surface modifiers. One would have understood in view of Andries that if desired, two or more surface modifiers can be used in combination (page 21, lines 11-12) and that based on the total volume of the composition: (b) from 0.5% to 20 %, or from 2% to 15% or 20% (w/v), or from 5% to 15% (w/v) of a wetting agent (page 25, lines 32-33). It would have been obvious to one of ordinary skill in the art to optimize the amount of the combined surface modifiers as taught by Andries to obtain the desired pharmaceutical composition. Determining optimal concentrations is routine experimentation and is practiced by one of ordinary skill. 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. In re Aller, 220 F. 2d 454, 105 USPQ 233 (CCPA 1955). In addition, according to the MPEP, “It is to be presumed also that skilled workers would as a matter of course, if they do not immediately obtain desired results, make certain experiments and adaptations, within the skill of the competent worker.” (MPEP 716.07).
Claim 28 is rejected under 35 U.S.C. 103 as being unpatentable over Andries et al. (WO2019012100A1, Published 01/17/2019; cited in the IDS filed 03/09/2023) in view of Pramanick et al. (Pharma Times, 45(3), 65, Published March 2013).
Applicant’s Invention
Andries renders obvious all the limitations of instant claim 1. Applicants claim 28 further adds the limitation wherein the high-molecular weight polyethylene glycol is PEG4000.
Determination of the scope and the content of the prior art
(MPEP §2141.01)
Regarding claim 28, Andries teaches the present invention is concerned with 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: (a) bedaquiline, or a pharmaceutically acceptable salt thereof, in micro- or nanoparticle form, and a surface modifier; and (b) a pharmaceutically acceptable aqueous carrier (page 3, lines 13-20). Andries further teach that suitable surface modifiers can be selected from polyethylene glycols (such as Carbowax 3550) (i.e., high molecular weight polyethylene glycol) (page 21, line 7).
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
Andries does not teach wherein the high-molecular weight polyethylene glycol is PEG4000. However, this deficiency is cured by Pramanick et al.
In the analogous art of parenteral pharmaceutical compositions, Pramanick teaches Excipients are typically the major components in a drug product. Many formulations contain only a small percentage of the active drug molecules. Pharmaceutical excipients or additives are compounds added to the finished drug products to serve a specific function (introduction paragraph). Pramanick also teaches Polyethylene glycol (PEG): It provides good cake structure and increases viscosity of water, wherein it is used as a co-solvent and viscosity modifier in parenteral (page 66, fifth paragraph). Pramanick further teaches PEG 4000 in table 6 as solvents and co-solvents used in injectables (page 66, table 6).
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been prima facie obvious to one of ordinary skill in the art before the time of filing to have PEG4000 present in the pharmaceutical composition of Andries. One of ordinary skill in the art would have been motivated to do so because Pramanick teaches Polyethylene glycol (PEG): It provides good cake structure and increases viscosity of water, wherein it is used as a co-solvent and viscosity modifier in parenteral (page 66, fifth paragraph). Pramanick further teaches PEG 4000 in table 6 as solvents and co-solvents used in injectables (page 66, table 6). The skilled artisan would have had a reasonable expectation of success because Andries teaches the present invention is concerned with a pharmaceutical composition for administration by intramuscular or subcutaneous injection (i.e., parenteral) and Pramanick teaches using PEG 4000 as solvents and co-solvents in injectables, therefore, PEG4000 is suitable for intramuscular or subcutaneous injections which are parenteral.
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 1-7 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 5-10 and 26 of copending Application No. 18/004,464 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘464 application claims render obvious the instant claims.
Inter alia the claims of the ‘464 application embrace A pharmaceutical composition for administration by intramuscular or subcutaneous injection, comprising a therapeutically effective amount of an active pharmaceutical ingredient, or a pharmaceutically acceptable salt thereof, in the form of a suspension of micro- or nanoparticles comprising:(a) an active pharmaceutical ingredient, or a pharmaceutically acceptable salt thereof, in micro- or nanoparticle form, and a surface modifier; and (b) a pharmaceutically acceptable aqueous carrier, wherein the surface modifier comprises a high molecular weight polyethylene glycol. The ‘464 application also embraces wherein the surface modifier comprises at least 75% by weight PEG4000 and the remainder is one or more other suitable surface modifiers; wherein the one or more other suitable surface modifiers are poloxamers, a-tocopheryl polyethylene glycol succinates, polyoxyethylene sorbitan fatty acid esters, or salts of negatively charged phospholipids. The ‘464 application further embraces wherein the average effective particle of the active pharmaceutical ingredient, or a pharmaceutically acceptable salt thereof, micro- or nanoparticles is below about 50µm; wherein the pharmaceutical composition comprises by weight based on the total volume of the pharmaceutical composition: (a) from 10% to 70% (w/v), of active pharmaceutical ingredient (or pharmaceutically acceptable salt thereof, but where the w/v is calculated on the basis of its non-salt form); (b) from 0.5% to 20 % (w/v), of a wetting agent or surface modifier; (c) from 0% to 10% (w/v), of one or more buffering agents; (d) from 0% to 20 % (w/v), of a isotonizing agent (e) from 0% to 2% (w/v) preservatives; and (f) water for injection q.s. ad 100%. The ‘464 application continues to embrace wherein the active pharmaceutical ingredient is bedaquiline.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 27-28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 5-10 and 26 of copending Application No. 18/004,464 in view of Pramanick et al. (Pharma Times, 45(3), 65, Published March 2013).
The relevant limitations of the ‘464 application are set forth.
The ‘464 application does not embrace wherein the high-molecular weight polyethylene glycol has a molecular weight of 1000 to 8000. The ‘464 application also does not embrace wherein the high-molecular weight polyethylene glycol is PEG4000.
However, Pramanick teaches Excipients are typically the major components in a drug product. Many formulations contain only a small percentage of the active drug molecules. Pharmaceutical excipients or additives are compounds added to the finished drug products to serve a specific function (introduction paragraph). Pramanick also teaches Polyethylene glycol (PEG): It provides good cake structure and increases viscosity of water, wherein it is used as a co-solvent and viscosity modifier in parenteral (page 66, fifth paragraph). Pramanick further teaches PEG 4000 in table 6 as solvents and co-solvents used in injectables (page 66, table 6).
It would have been prima facie obvious to one of ordinary skill in the art before the time of filing to have PEG4000 present in the pharmaceutical composition of ‘464 application. One of ordinary skill in the art would have been motivated to do so because Pramanick teaches Polyethylene glycol (PEG): It provides good cake structure and increases viscosity of water, wherein it is used as a co-solvent and viscosity modifier in parenteral (page 66, fifth paragraph). Pramanick further teaches PEG 4000 in table 6 as solvents and co-solvents used in injectables (page 66, table 6). The skilled artisan would have had a reasonable expectation of success because ‘464 application teaches the present invention is concerned with a pharmaceutical composition for administration by intramuscular or subcutaneous injection (i.e., parenteral) and Pramanick teaches using PEG 4000 as solvents and co-solvents in injectables, therefore, PEG4000 is suitable for intramuscular or subcutaneous injections which are parenteral.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AFUA BAMFOAA BOATENG whose telephone number is (703)756-1358. The examiner can normally be reached Monday - Friday 9:00am - 5:00pm.
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AFUA BAMFOAA BOATENGExaminer, Art Unit 1617
/ALI SOROUSH/Supervisory Patent Examiner, Art Unit 1614