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 without traverse of Group I, claims 1,5-10 and 16-19 in the reply filed on 01/27/2026 is acknowledged.
Claims 2, 11-12, and 20-27 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Groups II, III, and IV, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 01/27/2026.
Status of the Claims
Claims 2-4 11-15 and 20-27 have been cancelled.
Claims 1, 5-10 and 16-19 are pending and 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, 09/04/2025, 10/13/2025, and 01/05/2026 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, 5-10, and 16-19 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 1 recites the limitation "after sterilization" in line 7. There is insufficient antecedent basis for this limitation in the claim as the claim does not recite a sterilization step.
Claim 6 recites “PEG4000 of the pharmaceutical composition” in line 2. This language is indefinite because it is not clear if the PEG4000 is referring to the high molecular weight polyethylene glycol of claim 1 or is the PEG4000 in addition to the high molecular weight polyethylene glycol of claim 1, as no article was recited before “PEG4000”.
Claim 5 which is incorporated into claim 10 recites the limitation of a “pharmaceutical acceptable aqueous carrier”. There is no recitation of a “pharmaceutical acceptable aqueous carrier” in claim 10, therefore it is not clear if that limitation of a “pharmaceutical acceptable aqueous carrier” is still present in the formulation and if present, in what amounts is it present.
Claim 10 recites “of active pharmaceutical ingredient” in line 3. This language renders the claim indefinite because it is not clear if the active pharmaceutical ingredient of claim 10 is referring to the active pharmaceutical ingredient of claim 1 or is it in addition to the active pharmaceutical ingredient of claim 1, as no article was recited before “active pharmaceutical ingredient”.
Claim 10 recites “of a wetting agent or surface modifier” in line 6. This language renders the claim indefinite because it is not clear if the wetting agent or surface modifier of claim 10 is referring to the surface modifier of claim 1 which is a high molecular weight polyethylene glycol or is it in addition to high molecular weight polyethylene glycol of claim 1.
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, 5, 7-10, 16, and 18 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 method of administering a pharmaceutical composition to a patient by intramuscular or subcutaneous injection, wherein said pharmaceutical composition comprises a surface modifier that is a high molecular weight polyethylene glycol and an active pharmaceutical ingredient, or a pharmaceutically acceptable salt thereof, in the form of a suspension of micro- or nano-particles, wherein the high molecular weight polyethylene glycol assists in re-suspending said pharmaceutical composition after sterilization.
Determination of the scope and the content of the prior art
(MPEP §2141.01)
Regarding claims 1, 5 and 18, 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). Andries also teaches the compositions of the invention may be particularly suitable in a method of treating a subject infected with Mycobacterium leprae or the latent/dormant form of Mycobacterium tuberculosis. Such methods of treating a subject infected with pathogenic mycobacteria comprise the administration, by intramuscular or subcutaneous injection, of a therapeutically effective amount of a pharmaceutical composition as specified above or hereinafter (page 4, lines 20-25).
Regarding claims 7-8, 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 9, 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 10, Andries teaches a composition according to claims 1 or 2, comprising 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; but where the w/v is calculated on the basis of its non-salt form); (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% (claim 7).
Regarding claim 16, 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).
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 have a method of administering a pharmaceutical composition to a patient by intramuscular or subcutaneous injection, wherein said pharmaceutical composition comprises a surface modifier that is a high molecular weight polyethylene glycol and an active pharmaceutical ingredient, or a pharmaceutically acceptable salt thereof, in the form of a suspension of micro- or nano-particles, wherein the high molecular weight polyethylene glycol assists in re-suspending said pharmaceutical composition after sterilization because Andries teaches and contemplates all the elements required to make the pharmaceutical composition.
With regards to claim 1, wherein the high molecular weight polyethylene glycol assists in re-suspending said pharmaceutical composition after sterilization, Andries 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), but do not explicitly disclose that the high molecular weight polyethylene glycol assists in re-suspending said pharmaceutical composition after sterilization as claimed. However, such property must necessarily be present. Where, as here, the claimed and prior art products are identical or substantially identical, or are produced by identical or substantially identical processes, the PTO can require an Applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of the claimed product. See In re Ludtke, 441 F.2d 660, 169 USPQ 563 (CCPA 1971). Whether the rejection is based on "inherency" under 35 USC 102, on "prima facie obviousness" under 35 USC 103, jointly or alternatively, the burden of proof is the same, and its fairness is evidenced by the PTO's inability to manufacture products or to obtain and compare prior art products. In re Best, Bolton, and Shaw, 195 USPQ 430, 433 (CCPA 1977) citing In re Brown, 59 CCPA 1036, 459 F.2d 531, 173 USPQ 685 (1972).
Claims 6 and 17 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) in view of Mundhra et al. (US20170027933A1, Published 02/02/2017).
Applicant’s Invention
Andries renders obvious all the limitations of instant claim 1. Applicants claim 6 further adds the limitation wherein the surface modifier comprises at least 75% by weight PEG4000 of the pharmaceutical composition and the remainder is one or more other suitable surface modifiers. Applicants claim 17 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 6 and 17, 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 surface modifier comprises at least 75% by weight PEG4000 of the pharmaceutical composition and the remainder is one or more other suitable surface modifiers (claim 6). Andries also does not teach wherein the high-molecular weight polyethylene glycol is PEG4000 (claim 17). However, this deficiency is cured by Mundhra et al.
In the analogous art of parenteral pharmaceutical compositions for administration to a subject, Mundhra teaches a suitable combination of polymers, namely wetting agent and stabilizer, is required to manufacture a stable suspension. Wetting agents can be selected from a class of non-ionic and anionic surfactants (paragraph [0024]). Mundhra also teaches representative stabilizers include, but are not limited to, polyethylene glycols (paragraph [0025]), wherein an example of combination of polymers includes a polysorbate, for example, polysorbate 20 or polysorbate 60 as wetting agent and a polyethylene glycol (PEG), for example, PEG 3350, PEG4000 or PEG8000 as stabilizer (paragraph [0026]). Mundhra further teaches the compositions of the present invention may be administered by subcutaneous or intramuscular injection (paragraph [0040]).
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 Mundhra teaches a suitable combination of polymers, namely wetting agent and stabilizer, is required to manufacture a stable suspension (paragraph [0024]), wherein stabilizers include, but are not limited to, polyethylene glycols (paragraph [0025]), wherein an example of combination of polymers includes a polysorbate, for example, polysorbate 20 or polysorbate 60 as wetting agent and a polyethylene glycol (PEG), for example, PEG 3350, PEG4000 or PEG8000 as stabilizer (paragraph [0026]). Mundhra further teaches the compositions of the present invention may be administered by subcutaneous or intramuscular injection (paragraph [0040]). 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) in the form of a suspension and Mundhra teaches using PEG4000 as stabilizers for a stable suspension administered by subcutaneous or intramuscular injection, therefore, PEG4000 is suitable as a stabilizer for intramuscular or subcutaneous injections in suspension form.
With regards to claim 6, 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 19 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 Twose (Pharma’s Almanac, Published 10/02/2018).
Applicant’s Invention
Andries renders obvious all the limitations of instant claim 1. Applicants claim 19 further adds the limitation wherein the sterilizing is autoclaving.
Determination of the scope and the content of the prior art
(MPEP §2141.01)
Regarding claim 19, 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 sterilizing is autoclaving. However this deficiency is cured by Twose et al.
In the analogous art of injectable drugs, Twose teaches to ensure patient safety, parenteral/injectable drug products must be sterilized to destroy any potential microbial contaminants (fungi, bacteria)(Numerous Sterilization Methods paragraph 1). Twose also teaches The most common sterilization method involves heating under pressure in the presence of water to generate steam; this method is recommended by various pharmacopeias. Generally, steam sterilization is performed in an autoclave and can be used for drug products, medical devices, plastic bags and other single-use equipment, glass containers, surgical dressings and more )(Numerous Sterilization Methods paragraph 2).
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 sterilize Andries’ pharmaceutical composition. The artisan of ordinary skill would have been motivated to do so because Twose teaches that parenteral/injectable drug product should be sterilized to destroy any potential microbial contaminants to ensure patient safety. The skilled artisan would have had a reasonable expectation of success because Andries teaches a pharmaceutical composition for administration by intramuscular or subcutaneous injection and Twose teaches the importance of sterilizing parenteral/injectable drug products.
Claims 1, 5-7, and 16-17 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (CN1582909A, Published 02/23/2005).
Applicant’s Invention
Applicants’ claims are drawn to A method of administering a pharmaceutical composition to a patient by intramuscular or subcutaneous injection, wherein said pharmaceutical composition comprises a surface modifier that is a high molecular weight polyethylene glycol and an active pharmaceutical ingredient, or a pharmaceutically acceptable salt thereof, in the form of a suspension of micro- or nano-particles, wherein the high molecular weight polyethylene glycol assists in re-suspending said pharmaceutical composition after sterilization.
Determination of the scope and the content of the prior art
(MPEP §2141.01)
Regarding claims 1, 5, and 16-17, Wang teaches in Example 7, Take 1g florfenicol (i.e., active pharmaceutical ingredient), 1ml formal glycerine, 0.8g PEG 4000 (i.e., surface modifier, high molecular weight polyethylene glycol), dissolve them at 90 ℃, cool them, and stir until viscous. Add 7ml of water for injection (i.e., pharmaceutically acceptable aqueous carrier). After the florfenicol crystals have settled, add 0.2g polymyxin E sulfate, stir, and dissolve to obtain the final product (page 11, last paragraph). Wang also teaches that this preparation can be administered by injection (page 6, first paragraph), wherein the preparation is used for the control of animal microorganism infectious disease by subcutaneous or intramuscular injection (claim 9). Wang further teaches that florfenicol with tylosin or tiamulin-like drugs to prepare a solution, suspension (where the active ingredients exist as suspended microparticles) (page 7, third paragraph).
Regarding claims 6-7, Wang teaches the use of stabilizing agents such as polyethylene glycol (PEG) with a molecular weight that is greater than 1000, polyoxyethylene sorbitan fatty acid esters, wherein they can be used in combination of two or more (page 8, second paragraph). Wang also teaches stabilizers can be used in the amount of 0-15%(w/v) (page 7, last paragraph).
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
Wang 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 Wang 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 have a method of administering a pharmaceutical composition to a patient by intramuscular or subcutaneous injection, wherein said pharmaceutical composition comprises a surface modifier that is a high molecular weight polyethylene glycol and an active pharmaceutical ingredient, or a pharmaceutically acceptable salt thereof, in the form of a suspension of micro- or nano-particles, wherein the high molecular weight polyethylene glycol assists in re-suspending said pharmaceutical composition after sterilization because Wang teaches and contemplates all the elements required to make the pharmaceutical composition.
With regards to claim 1, wherein the high molecular weight polyethylene glycol assists in re-suspending said pharmaceutical composition after sterilization, Wang teaches the use of stabilizing agents such as polyethylene glycol (PEG) with a molecular weight that is greater than 1000 (page 7, last paragraph), but do not explicitly disclose that the high molecular weight polyethylene glycol assists in re-suspending said pharmaceutical composition after sterilization as claimed. However, such property must necessarily be present. Where, as here, the claimed and prior art products are identical or substantially identical, or are produced by identical or substantially identical processes, the PTO can require an Applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of the claimed product. See In re Ludtke, 441 F.2d 660, 169 USPQ 563 (CCPA 1971). Whether the rejection is based on "inherency" under 35 USC 102, on "prima facie obviousness" under 35 USC 103, jointly or alternatively, the burden of proof is the same, and its fairness is evidenced by the PTO's inability to manufacture products or to obtain and compare prior art products. In re Best, Bolton, and Shaw, 195 USPQ 430, 433 (CCPA 1977) citing In re Brown, 59 CCPA 1036, 459 F.2d 531, 173 USPQ 685 (1972).
With regards to claim 1, wherein the pharmaceutical composition is in the form of a suspension of micro-or nano- particles, it would have been obvious to one of ordinary skill in the art to have Wang’s Example 7 as a suspension of micro- or nano- particles. One would have understood in view of Wang that in Example 7 the florfenicol forms crystals. Wang further teaches that florfenicol with tylosin or tiamulin-like drugs to prepare a solution, suspension (where the active ingredients exist as suspended microparticles) (page 7, third paragraph). Therefore it would have been obvious to one of ordinary skill in the art to have Wang’s Example 7 as a suspension of micro- or nano-particles because Wang teaches that the florfenicol can be prepared in a solution suspension where the active ingredients exist as suspended microparticles (page 7, third paragraph).
With regards to the limitation of claim 1, wherein the pharmaceutical composition is to be administered as a intramuscular or subcutaneous injection, it would have been obvious to one of ordinary skill in the art to administer Wang’s Example 7 as a intramuscular or subcutaneous injection. One would have understood in view of Wang that this preparation can be administered by injection (page 6, first paragraph), wherein the preparation is used for the control of animal microorganism infectious disease by subcutaneous or intramuscular injection (claim 9). Therefore it would have been obvious to one of ordinary skill in the art to administer Wang’s Example 7 as a intramuscular or subcutaneous injection because Wang teaches that the preparation can be administered by an subcutaneous or intramuscular injection.
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (CN1582909A, Published 02/23/2005) in view of in view of Twose (Pharma’s Almanac, Published 10/02/2018).
Applicant’s Invention
Wang renders obvious all the limitations of instant claim 1. Applicants claim 19 further adds the limitation wherein the sterilizing is autoclaving.
Determination of the scope and the content of the prior art
(MPEP §2141.01)
Regarding claim 19, Wang teaches in Example 7, Take 1g florfenicol (i.e., active pharmaceutical ingredient), 1ml formal glycerine, 0.8g PEG 4000 (i.e., surface modifier, high molecular weight polyethylene glycol), dissolve them at 90 ℃, cool them, and stir until viscous. Add 7ml of water for injection (i.e., pharmaceutically acceptable aqueous carrier). After the florfenicol crystals have settled (i.e., form a suspension of micro-or nano- particles), add 0.2g polymyxin E sulfate, stir, and dissolve to obtain the final product (page 11, last paragraph). Wang also teaches that this preparation can be administered by injection (page 6, first paragraph), wherein the preparation is used for the control of animal microorganism infectious disease by subcutaneous or intramuscular injection (claim 9). Wang further teaches that florfenicol with tylosin or tiamulin-like drugs to prepare a solution, suspension (where the active ingredients exist as suspended microparticles) (page 7, third paragraph).
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
Wang does not teach wherein the sterilizing is autoclaving. However this deficiency is cured by Twose et al.
In the analogous art of injectable drugs, Twose teaches to ensure patient safety, parenteral/injectable drug products must be sterilized to destroy any potential microbial contaminants (fungi, bacteria)(Numerous Sterilization Methods paragraph 1). Twose also teaches The most common sterilization method involves heating under pressure in the presence of water to generate steam; this method is recommended by various pharmacopeias. Generally, steam sterilization is performed in an autoclave and can be used for drug products, medical devices, plastic bags and other single-use equipment, glass containers, surgical dressings and more )(Numerous Sterilization Methods paragraph 2).
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 sterilize Wang’s pharmaceutical composition. The artisan of ordinary skill would have been motivated to do so because Twose teaches that parenteral/injectable drug product should be sterilized to destroy any potential microbial contaminants to ensure patient safety. The skilled artisan would have had a reasonable expectation of success because Wang teaches a pharmaceutical composition for administration by intramuscular or subcutaneous injection and Twose teaches the importance of sterilizing parenteral/injectable drug products.
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, 5, 9-10, and 18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. US12171887.
Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘887 patent claims render obvious the instant claims.
Inter alia the claims of the ‘887 patent embraces a method for treating a subject infected with a pathogenic mycobacterial infection comprising administering to the subject, by intramuscular or subcutaneous injection, a composition in the form of a suspension comprising: micro-or nanoparticles of bedaquiline, or a pharmaceutically acceptable salt thereof, and a surface modifier; and a pharmaceutically acceptable aqueous carrier, wherein the bedaquiline is the only active ingredient in the suspension. The ‘887 patent also embraces wherein bedaquiline is in its non-salt or free form or in the form of a fumarate salt; wherein the average effective particle size of the bedaquiline, or the pharmaceutically acceptable salt thereof, micro-or nanoparticles is below about 50 μm. The ‘887 continues to embrace wherein the surface modifier is selected from the group of poloxamers, a-tocopherol polyethylene glycol succinates, polyoxyethylene sorbitan fatty acid esters, and salts for negatively charged phospholipids; wherein the surface modifier is selected from Pluronic™ F108, Vitamin E TGPS, Tween™ 80, and Lipoid™ EPG. The ‘887 patent further embraces wherein the composition comprises by weight based on the total volume of the composition: (a) from 10% to 70%(w/v) of bedaquiline (or a 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; (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 qs as 100%.
Claims 6-8 and 16-17 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. US12171887B2 in view of Mundhra et al. (US20170027933A1, Published 02/02/2017).
The relevant limitations of the ‘887 patent are set forth.
The ‘887 patent does not embrace wherein the surface modifier comprises at least 75% by weight PEG4000 of the pharmaceutical composition. The ‘887 patent also does not embrace wherein the high-molecular weight polyethylene glycol has a molecular weight of above 1000 to 8000.
However, In the analogous art of parenteral pharmaceutical compositions for administration to a subject, Mundhra teaches a suitable combination of polymers, namely wetting agent and stabilizer, is required to manufacture a stable suspension. Wetting agents can be selected from a class of non-ionic and anionic surfactants (paragraph [0024]). Mundhra also teaches representative stabilizers include, but are not limited to, polyethylene glycols (paragraph [0025]), wherein an example of combination of polymers includes a polysorbate, for example, polysorbate 20 or polysorbate 60 as wetting agent and a polyethylene glycol (PEG), for example, PEG 3350, PEG4000 or PEG8000 as stabilizer (paragraph [0026]). Mundhra further teaches the compositions of the present invention may be administered by subcutaneous or intramuscular injection (paragraph [0040]).
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 the ‘887 patent. One of ordinary skill in the art would have been motivated to do so because Mundhra teaches a suitable combination of polymers, namely wetting agent and stabilizer, is required to manufacture a stable suspension (paragraph [0024]), wherein stabilizers include, but are not limited to, polyethylene glycols (paragraph [0025]), wherein an example of combination of polymers includes a polysorbate, for example, polysorbate 20 or polysorbate 60 as wetting agent and a polyethylene glycol (PEG), for example, PEG 3350, PEG4000 or PEG8000 as stabilizer (paragraph [0026]). Mundhra further teaches the compositions of the present invention may be administered by subcutaneous or intramuscular injection (paragraph [0040]). The skilled artisan would have had a reasonable expectation of success because the ‘887 patent teaches the present invention is concerned with a pharmaceutical composition for administration by intramuscular or subcutaneous injection (i.e., parenteral) in the form of a suspension and Mundhra teaches using PEG4000 as stabilizers for a stable suspension administered by subcutaneous or intramuscular injection, therefore, PEG4000 is suitable as a stabilizer for intramuscular or subcutaneous injections in suspension form.
Claim 19 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. US12171887B2 in view of Twose (Pharma’s Almanac, Published 10/02/2018).
The relevant limitations of the ‘887 patent are set forth.
The ‘887 patent does not embrace wherein the sterilizing is autoclaving.
However, Twose teaches to ensure patient safety, parenteral/injectable drug products must be sterilized to destroy any potential microbial contaminants (fungi, bacteria)(Numerous Sterilization Methods paragraph 1). Twose also teaches The most common sterilization method involves heating under pressure in the presence of water to generate steam; this method is recommended by various pharmacopeias. Generally, steam sterilization is performed in an autoclave and can be used for drug products, medical devices, plastic bags and other single-use equipment, glass containers, surgical dressings and more )(Numerous Sterilization Methods paragraph 2).
It would have been prima facie obvious to one of ordinary skill in the art before the time of filing to sterilize ‘887 pharmaceutical composition. The artisan of ordinary skill would have been motivated to do so because Twose teaches that parenteral/injectable drug product should be sterilized to destroy any potential microbial contaminants to ensure patient safety. The skilled artisan would have had a reasonable expectation of success because the ‘887 patent teaches a pharmaceutical composition for administration by intramuscular or subcutaneous injection and Twose teaches the importance of sterilizing parenteral/injectable drug products.
Conclusion
No claims allowed.
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AFUA BAMFOAA BOATENGExaminer, Art Unit 1617
/ALI SOROUSH/Supervisory Patent Examiner, Art Unit 1614