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 1-12, 16 and 17, in the reply filed on 1/20/26 is acknowledged.
Claims 13-15 and 18-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 1/20/26.
Claim Status:
Claim 20 is cancelled.
Claims 1-19 are pending.
Claims 13-15, 18 and 19 are withdrawn.
Claims 1-12, 16 and 17 are presented for examination on the merits.
Priority
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Claim 1 of the instant application is broader in scope than the disclosure of PCT/US22/70941, which excludes PLGA as the biodegradable polymer ([0004]; claim 1). Similarly, provisional applications 63483100 and 63510966 exclude PLGA as well. Consequently, embodiments that do not exclude PLGA as the biodegradable polymer appear to be the subject matter that makes this application a CIP application. Accordingly, the effective filing date is 9/14/2023.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on 11/20/23 and 6/28/24 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Objections
Claim 1 is objected to because of the following informalities: claim 1 uses quotation marks “POE”. The Examiner believes this to be grammatically improper as the acronym is understood for the poly(ortho ester) and there is no need to quote a source. Appropriate correction is required.
Claim 5 is objected to because of the following informalities: claim 5 does not end in a period.
Applicant is advised that should claim 10 be found allowable, claim 12 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
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 1-12, 16 and 17 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.
In the present instance, these claims contain parentheses which raises the question as to which term is required by the claim because the subject matter in the parentheses is not identical in scope. Claim 1 recites a particle size of between about 20 μm to about 60 μm (D50), and in contrast claim 5 recites: between about 25 μm (D50) and about 50 μm (D50). Also, claim 8 recites about 20 μm to about 45 μm (D50), claim 11 recites about 20 μm to about 55 μm (D50) and claim 16 recites about 20 μm to about 45 μm (D50). The Examiner is uncertain if “(D50)” is supposed to modify the entire range or just the values indicated. Furthermore, the claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by parenthesis (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. The Examiner suggests deleting “(D50)” and inserting language such as: wherein the polymer microspheres have a D50 particle size of between about…Dependent claims are rejected as indefinite because they are dependent upon an indefinite claim.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 3, 6-10 and 12 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Minrovic et al. (WO2022198167 published September 22, 2022; IDS filed 6/28/24).
The applied reference has a common inventor and common assignee with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
Regarding claim 1, Minrovic et al. disclose in claim 1:
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Table 1 discloses an example with a D50 particle size of 31 [0041]. Table 2 discloses examples with a D50 particle size of 29, 30 and 26 [0045].
Regarding claim 3, Minrovic et al. disclose in claim 3:
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Regarding claims 6-7, Minrovic et al. disclose in claims 6-7:
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Regarding claims 8-10 and 12, Minrovic et al. disclose in claims 6-7:
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Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 1-12, 16 and 17 are rejected under 35 U.S.C. 103 as being obvious over Minrovic et al. (WO2022198167).
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.
The applied reference has several common inventors and common assignee with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
Applicant claims, for example:
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Level of Ordinary Skill in the Art
(MPEP 2141.03)
MPEP 2141.03 (I) states: “The “hypothetical ‘person having ordinary skill in the art’ to which the claimed subject matter pertains would, of necessity have the capability of understanding the scientific and engineering principles applicable to the pertinent art.” Ex parte Hiyamizu, 10 USPQ2d 1393, 1394 (Bd. Pat. App. & Inter. 1988). The level of skill is that of a pharmaceutical formulation research scientist, as is the case here, then one can assume comfortably that such an educated artisan will draw conventional ideas from pharmaceutical formulation techniques, materials, active agents and their derivatives and procedures— without being told to do so. The pharmaceutical formulation scientist has expertise in excipient compatibility, stability testing, drug delivery systems, and regulatory guidelines (cGMP), enabling them to optimize bioavailability and product shelf-life.
In addition, the prior art itself reflects an appropriate level (MPEP 2141.03(II)).
Determination of the scope and content of the prior art
(MPEP 2141.01)
It is well settled that “a disclosure that anticipates under § 102 also renders the claim invalid under §103, for anticipation is the epitome of obviousness. See MPEP 1207.03(a)(II) states: “"lack of novelty is the epitome of obviousness." May, 574 F.2d at 1089, 197 USPQ at 607 (citing In re Pearson, 494 F.2d 1399, 1402, 181 USPQ 641, 644 (CCPA 1974))”. Accordingly, the claims rejected under §102 above, 1, 3, 6-10 and 12, are also invalid under §103.
The reference of Minrovic et al. is discussed in detail above and that discussion is incorporated by reference.
Regarding claim 2, Minrovic et al. teach naltrexone HCl salt [0016].
Regarding claim 4, Minrovic et al. teach a CHDM:TEG ratio of about 88 to about 12 (Claim 5).
Regarding claim 5, Minorvic et al. teach particles wherein the polymer microspheres have an average particle size of between about 25 μm to about 55 μm (D50) (Claims 1, 4 and 5).
Regarding claim 16, Minrovic et al. teach in claim 16:
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Overlapping ranges of drug load and particle size are rendered obvious. See MPEP 2144.05(I): In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976).
Regarding claims 10, 12 and 17, Minrovic et al. teach pharmaceutical compositions (Claim 14).
Ascertainment of the difference between the prior art and the claims
(MPEP 2141.02) and Finding of prima facie obviousness
Rational and Motivation (MPEP 2142-2143)
1. The difference between the instant application and Minrovic et al. is that Minrovic et al. do not expressly teach a cyclohexanedimethanol:triethylene glycol (CHDM:TEG) co-polymer in a ratio of about 80: about 20. However, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Minrovic et al. to use a cyclohexanedimethanol:triethylene glycol (CHDM:TEG) co-polymer in a ratio of about 80: about 20 and produce the instant invention.
One of ordinary skill in the art would have been motivated to do this because for the following sound articulated reasoning with rational underpinning based upon the evidence. As noted above, Minrovic et al. teach a CHDM:TEG ratio of about 88 to about 12 (Claim 5). Given a reasonable 10% variance for the term “about” that would mean a lower CHDM amount of 80 is within the scope of the invention and the corresponding amount of TEG would be then 20. Therefore, it is merely routine optimization by the ordinary artisan of the CHDM:TEG ratio as suggested by Minrovic et al. to arrive at a co-polymer ratio of about 80:about 20 with a reasonable expectation of success.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103.
Claims 1-12, 16 and 17 are rejected under 35 U.S.C. 103 as being obvious over Kim (US20200261878) and Zale et al. (US7799345) and Bai et al. (Journal of Applied Polymer Science, Vol. 80, 1630–1642 (2001)).
Applicant claims, for example:
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Determination of the scope and content of the prior art
(MPEP 2141.01)
Regarding claims 1, 2, 5, 8, 10-12, 16 and 17, Kim teaches spherical microparticles with an average particle diameter of 20 µm to 70 µm, which the Examiner interprets to read on the D50 and reads on a particle size of between about 20 μm to about 60 μm (D50) a particle size of between about 25 μm (D50) and about 50 μm a
particle size of about 20 μm to about 45 μm (D50) a particle size of between about 20 μm to about 55 μm (D50), (See MPEP 2144.05(I): In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976)),
comprising a biodegradable polymer and a drug (Claim 1) where the drug is naltrexone (Claim 2) and the biodegradable polymer is a polyorthoester (Claim 6) and compositions of the microparticles (Claim 8), which would be pharmaceutical compositions comprising the spherical microparticle formulation.
Regarding claims 1, 2, 5, 8, 10-12, 16 and 17, Zale et al. teach microparticles of naltrexone and polyorthoester (Claim 1) wherein the mass median diameter of the microparticles is in the range of from about 20 µm to about 150 µm (Claim 8). Zale et al. teach a drug loading ranging from about 35% to about 39% for a process with 400 grams active agent and 600 grams of polymer (theoretical drug loading of 40%) (Example 7, column 16, lines 59-65).
Regarding claims 3, 4, 6, 7, 11 and 16, Bai et al. teach fabrication of polyorthoester microspheres where “All eight kinds of POE polymers used in this study are shown able to form microspheres under proposed fabrication conditions.” And: “POE containing 1,6-hexanediol diglycolide (HDdiGL) microspheres have the highest BSA release rate after a 20-day test through a combination of surface erosion and diffusion mechanisms. POE containing a high percentage of the trans-cyclohexanedimethanol (CDM) segment tends to yield microspheres with a lower release rate because of its hydrophobic nature.” (Abstract; Figure 2) Bai et al. show in Table 1 (Page 1632):
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Ascertainment of the difference between the prior art and the claims
(MPEP 2141.02) and Finding of prima facie obviousness
Rational and Motivation (MPEP 2142-2143)
The difference between the instant application and Kim is that Kim do not expressly teach wherein each polymer microsphere comprises a drug load of naltrexone or a salt thereof of greater than 40% by weight of the polymer microsphere or about 45% to about 60% by weight of the polymer microsphere; wherein the POE comprises a cyclohexanedimethanol:triethylene glycol (CHDM:TEG) co-polymer in a ratio of about 80: about 20; wherein the POE comprises a cyclohexanedimethanol:triethylene glycol:triethylene glycol glycolide (CHDM:TEG:TEG-GL) tri-block polymer in a ratio of about 88: about 10: about 2. This deficiency in Kim is cured by the teachings of Zale et al. and Bai.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the naltrexone polyorthoester spherical microparticles of Kim wherein each polymer microsphere comprises a drug load of naltrexone or a salt thereof of greater than 40% by weight of the polymer microsphere or about 45% to about 60% by weight of the polymer microsphere; wherein the POE comprises a cyclohexanedimethanol:triethylene glycol (CHDM:TEG) co-polymer in a ratio of about 80: about 20; wherein the POE comprises a cyclohexanedimethanol:triethylene glycol:triethylene glycol glycolide (CHDM:TEG:TEG-GL) tri-block polymer in a ratio of about 88: about 10: about 2, as suggested by Zale et al. and Bai, and produce the instant invention. One of ordinary skill in the art would have been motivated to do this because for the following sound articulated reasoning with rational underpinning based upon the evidence. As noted above, Bai teaches the claimed microsphere formulation of claim 1 except for the drug load of naltrexone or salt thereof of greater than 40% by weight of the polymer microsphere. However, Zale et al. teach an expectation of about 39% loading from a process with 400 grams active agent and 600 grams of polymer (theoretical drug loading of 40%). Not only does the term “about” provide for values greater than 39% such as 41% but also the loading would be result effective variable where a process with 500 grams of naltrexone and 500 grams of polymer would be expected to provide a 50% by weight loading of naltrexone or salt thereof with a reasonable expectation of success. Thus, a loading of greater than 40% by weight of the polymer microsphere or about 45% to about 60% by weight of the polymer microsphere is merely routine optimization by the ordinary artisan. Selection of the salt of naltrexone is within the skill of the ordinary artisan in the pharmaceutical arts.
As noted above, Kim and Zale et al. teach polyorthoesters for the biodegradable polymer but do not specify any particular polyorthoester. However, Bai teaches polyorthoester co-polymers comprising cyclohexanedimethanol:triethylene glycol in a 75:20 ratio (Table II, POE2, POE3), which reasonable reads on co-polymer in a ratio of about 80:about 20, and tri-block co-polymers comprising CDM/TEG/TEGmGL 94/5/1 (Table 2, POE8) as well as CDM/TEG/CDMmLT 5 89/10/1 (POE4). Consequently, it is merely routine optimization to obtain a tri-block copolymer comprising a cyclohexanedimethanol:triethylene glycol:triethylene glycol glycolide (CHDM:TEG:TEG-GL) tri-block polymer in a ratio of about 88: about 10: about 2. Especially when Bai teaches that the GL amount influences the release rate (Abstract; page 1631, left column 1st paragraph; page 1639, left column 2nd and 3rd paragraphs). Thus, it is merely routine optimization to tune the microparticle for the desired release rate with a reasonable expectation of success.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103.
Conclusion
No claims are allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Maa et al. (NPL reference #3 on the IDS filed 11/20/23) teaches controlled release of naltrexone salt from disks and slabs of poly(ortho esters) (Page 22, Experimental Procedures, Preparation of devices) but not from microspheres.
Dinarvand et al. (AAPS PharmSciTech 2003; 4 (3) Article 34; 10 pages) teaches naltrexone microspheres of the polyester poly(L-lactide) with an average particle size of about 100 µm (Figure 2 (a)) and 46.8 and 54.1% drug loading (Table 1).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERNST V ARNOLD whose telephone number is (571)272-8509. The examiner can normally be reached M-F 7-3:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Brian Y Kwon can be reached at 571-272-0581. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ERNST V ARNOLD/Primary Examiner, Art Unit 1613