Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
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 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.
DETAILED ACTION
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 10/14/2025 has been entered.
Status of claims
Claims 1-42, 45-50, 53, and 62 have been canceled and claim 44 has been withdrawn. Claims 43, 51, 52, 54-61, and 63 are under examination in the instant office action.
Rejections withdrawn
Applicant’s amendments and arguments filed on 10/14/2025 are acknowledged and have been fully considered. Any rejection and/or objection not specifically addressed below is herein withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set of rejections and/or objections presently being applied to the instant application.
Rejections maintained
The following rejections of the claims are maintained for reasons of record and the following.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103(a) 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 43, 51, 52, 54-61, and 63 are rejected under 35 U.S.C. 103(a) as being unpatentable over O’Malley et al. (US 6,541,478 B1) in view of Weber et al. (US 2004/0254208 A1), Shashoua (US 5,994,392), Kaiko et al. (US 6,696,066 B2), Vergnault et al. (2003/0180359 A1), and Caruso et al. (US 2003/0065002 A1).
O’Malley et al. teach sustained release formulations of both naltrexone and bupropion, in forms of tablet or capsule for once daily or more administration, comprising about 12.5 mg (≤ about 12.5 mg) or about 25-50 mg of naltrexone and bupropion (abstract, column 4, line 22-24 and line 34-67, and column 5, line 65, and claims 1, 4, 5, 11, 14, 15, 18, and 19).
O’Malley et al. do not specify the same dosage of naltrexone (≤ about 12.5 mg vs the claimed about 8 mg in the instant claim 43).
This deficiency is cured by the rationale that a prima facie case of obviousness typically exists when the range of a claimed composition lies inside the range disclosed in the prior art, such as in the instant rejection.
The claimed range of dosage of naltrexone is about 8 mg and the range of dosage of naltrexone taught in the prior art is ≤ about 12.5 mg and therefor, includes the claimed range.
O’Malley et al. do not specify the dosage of bupropion (the instant claim 43).
This deficiency is cured by Weber et al. who teach sustained release tablet or capsule formulations for once daily or more administration comprising 50 mg of naltrexone and 90 mg of bupropion being formulated (abstract, paragraph 96, 107, 111, 210, 213, 223, 230, 234, and 236, and claims 11-3 and 9).
It would have been prima facie obvious at the time of the invention to a person of ordinary skill in the art to combine the teachings in O’Malley et al. and Weber et al. to specify 90 mg of bupropion being co-administrated with naltrexone. 90 mg of bupropion being co-administrated with naltrexone was well known as to a person of ordinary skill in the art at the time of the invention. The motivation for specifying it flows from its having been used in the prior art, and from its being recognized in the prior art as useful for the same purpose.
O’Malley et al. do not specify naltrexone and bupropion being in HCl salt forms (the instant claim 43).
This deficiency is cured by Shashoua who teaches naltrexone and bupropion being in HCl salt form in oral sustained release formulation (entire reference, especially abstract, column 15, line 64, column 18, line 9, and column 21, line 50-56).
It would have been prima facie obvious at the time of the invention to a person of ordinary skill in the art to combine the teachings in O’Malley et al. and Shashoua to specify naltrexone and bupropion in the composition taught by O’Malley et al. being in HCl salt forms. Naltrexone and bupropion being in HCl salt forms was well known as to a person of ordinary skill in the art at the time of the invention. The motivation for specifying it flows from its having been used in the prior art, and from its being recognized in the prior art as useful for the same purpose.
O’Malley et al. do not specify naltrexone release profile in claims 43 and 54-56, both naltrexone and bupropion sustained release comprising hydroxypropyl methyl cellulose (HPMC), hydroxypropyl cellulose (HPC), microcrystal cellulose (MCC), and lactose monohydrate in claims 43 and 63, and magnesium stearate in claims 57-60, and naltrexone and bupropion being separated by an inert layer in claim 61.
This deficiency is cured by Kaiko et al. who teach formulating sustained release opioid agonist and opioid antagonist via incorporation of a sustained release carrier into a matrix containing the opioid agonist and opioid antagonist or via a sustained release coating of a matrix containing the opioid agonist and opioid antagonist with the choice of coating material and matrix material such as HPMC and HPC and conventional pharmaceutically acceptable organic or inorganic carrier substances as excipients for tablets including lubricating agents such as magnesium stearate, MCC as a spheronizing agent, and a diluent (column 7, line 26-51, column 14, line 31-45, column 16, line 19 through column 17, line 45, the paragraph bridges column 18 and 19, column 21, line 24-27, column 21, line 38-47, the paragraph bridges column 22 and 23, and column 26, line 18-27); Vergnault et al. who teach layered tablet comprising a barrier layer between two active layers (figure 8 and paragraph 23) and lactose monohydrate as a diluent of table (paragraph 221); and Caruso et al. who teach controlled/sustained release oral tablet of opioid antagonist including naloxone, naltrexone, etc., formulated with controlled/sustained release polymer being HPMC and exemplified releasing of naloxone 52.5% at 1 hour, 78.0% at 2 hours, and 99.8% at 8 hours in formula 3 in paragraph 42 tested using USP apparatus 3 in gastrointestinal simulate at 37.5 °C (abstract, paragraph 12, 14, 42, and 43, and claim 1 and 10). It is reasonable to assume the release percentage being half of that at 1 hour, i.e., 26.25% at 0.5 hour. It is noted that the dissolution test condition taught by Caruso et al. is not the same as that of claimed, however as a practical matter, the Patent Office is not equipped to manufacture products by the myriad number of processes put before it and then obtain prior art products and make physical comparisons therewith.” In re Brown, 459 F.2d 531, 535, 173 USPQ 685, 688 (CCPA 1972). Please note that the Patent and Trademark Office is not equipped to conduct experimentation in order to determine whether Applicants’ indented material differs and, if so, to what extent, from that of the discussed reference. Therefore, with the showing of the reference teaching the dosage form having the same sustained-/immediate-/timed-release (the claimed sustained release is substantially the same as an immediate release according to the instant specification), the burden of establishing non-obviousness by objective evidence is shifted to the Applicants.
It would have been prima facie obvious at the time of the invention to a person of ordinary skill in the art to combine the teachings in O’Malley et al., Kaiko et al., and Caruso et al. to specify sustained release naloxone oral tablet releasing 52.5% at 1 hour, 78.0% at 2 hours, and 99.8% at 8 hours, and 26.25% at 0.5 hour and further modify based on Kaiko et al. to arrive at the specific release rate of about 85% at 2 hours in the instant claim 55 through routine optimization. Since both naloxone and naltrexone are suitable opioid antagonist, it would have been prima facie obvious at the time of the invention to a person of ordinary skill in the art to replace naloxone in formula 3 with naltrexone. Timed-/sustained-/immediate-release naloxone/naltrexone oral tablet releasing 52.5% at 1 hour, 78.0% at 2 hours, and 99.8% at 8 hours and 26.25% at 0.5 hour and formulating sustained release opioid agonist and opioid antagonist via incorporation of a sustained release carrier into a matrix containing the opioid agonist and opioid antagonist or via a sustained release coating of a matrix containing the opioid agonist and opioid antagonist were well known as to a person of ordinary skill in the art at the time of the invention. The motivation for specifying it flows from its having been used in the prior art, and from its being recognized in the prior art as useful for the same purpose. Furthermore, 62-90% of naltrexone release at 2 hours is claimed in the instant claim 43, the release rate of about 85% at 2 hours in the instant claim 55 over 78.0% at 2 hours taught by Caruso et al. is not established.
It would have been prima facie obvious at the time of the invention to a person of ordinary skill in the art to combine the teachings O’Malley et al., Kaiko et al., Vergnault et al., and Caruso et al. to specify controlled/sustained release of both naltrexone and bupropion in the composition taught by O’Malley et al. being formulated with HPMC, HPC, MCC, magnesium stearate, and lactose monohydrate as a diluent with a barrier layer between two active layers. Both naltrexone and bupropion being in form of sustained release and HPMC and HPC for formulating controlled/sustained release and MCC, magnesium stearate, and lactose monohydrate being a conventional pharmaceutically acceptable tableting excipients were well known to a person of ordinary skill in the art at the time of the invention. The motivation for specifying them flows from their having been used in the prior art, and from their being recognized in the prior art as useful for the same purpose.
Response to Applicants’ arguments:
Applicant’s argument of Caruso et al.’s teaching of naloxone release profile, not the claimed naltrexone release profile is basically the same as in the response dated 05/28/2024, thus the response discussed previously in the office action dated 08/15/2024 (page 14) applies here as well and is not persuasive for reason discussed.
Applicants argue that Weber et al. d not teach the claimed naltrexone release profile; Shashoua does not teach the claimed naltrexone and bupropion amounts in mg, the claimed excipients, and the claimed naltrexone release profile; Kaiko et al. do not teach the claimed four excipients and the claimed naltrexone release profile; Vergnault et al. do not teach the claimed naltrexone and bupropion, the claimed four excipients, and the claimed naltrexone release profile; and Caruso et al. do not teach the claimed naltrexone hydrochloride or bupropion hydrochloride.
However, this argument is not deemed persuasive. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Please refer to MPEP 2145.III, MPEP 2144.07, and MPEP 2143.02:
the test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art.
The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945)
A rationale to support a conclusion that a claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art.
Claims 43, 51, 52, 54-61, and 63 are rejected under 35 U.S.C. 103(a) as being unpatentable over Weber et al. (US 2004/0254208 A1) in view of Shashoua (US 5,994,392), Kaiko et al. (US 6,696,066 B2), Vergnault et al. (2003/0180359 A1), and Caruso et al. (US 2003/0065002 A1).
Weber et al. teach sustained release formulations in forms of tablet or capsule for once daily or more administration comprising 50 mg of naltrexone and 90 mg of bupropion being formulated with HPMC; wherein the dosage of naltrexone is 5-50 mg including 50 mg and naltrexone and bupropion are administrated simultaneously or separately (abstract, paragraph 23, 48, 49, 96, 107, 111, 120, 124, 147, 148, 210, 213, 223, 230, 234, and 236, and claims 11-3 and 9).
Weber et al. do not specify the same dosage of naltrexone (5-50 mg vs the claimed about 8 mg in the instant claim 43).
This deficiency is cured by the rationale that a prima facie case of obviousness typically exists when the range of a claimed composition lies inside the range disclosed in the prior art, such as in the instant rejection.
The claimed range of dosage of naltrexone is about 8 mg and the range of dosage of naltrexone taught in the prior art is 5-50 mg and therefor, includes the claimed range. Furthermore, about 4-50 mg of naltrexone was previously claimed (03/24/2020) and thus there is no criticality of the new claimed about 8 mg of naltrexone.
Weber et al. do not specify naltrexone and bupropion being in HCl salt forms (the instant claim 43).
This deficiency is cured by Shashoua whose teachings and the rationale are discussed above and applied in the same manner.
Weber et al. do not specify naltrexone release profile in claims 43 and 54-56, both naltrexone and bupropion sustained release comprising hydroxypropyl methyl cellulose (HPMC), hydroxypropyl cellulose (HPC), microcrystal cellulose (MCC), and lactose monohydrate in claims 43 and 63, and magnesium stearate in claims 57-60, and naltrexone and bupropion being separated by an inert layer in claim 61.
This deficiency is cured by Kaiko et al., Vergnault et al., and Caruso et al. whose teachings and the rationale are discussed above and applied in the same manner.
Response to Applicants’ arguments:
Argument regarding the 103 rejection is basically the same as the above 103 rejection, thus the response discussed above applies here as well and is not persuasive for reason discussed above.
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 obviousness-type 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); and 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 a nonstatutory double patenting ground provided the conflicting application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement.
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
Claims 43, 51, 52, 54-61, and 63 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 7,375,111 B2 and claim 1 of U.S. Patent No. 8,088,786 B2 in view of Shashoua (US 5,994,392), Kaiko et al. (US 6,696,066 B2), Vergnault et al. (2003/0180359 A1), and Caruso et al. (US 2003/0065002 A1).
The subject matter claimed in the instant application is fully disclosed in the patent and is covered by the patent since the patent and the application are claiming common subject matter, as follows:
The instant application claims 43, 51, 52, 54-61, and 63 recite an oral dosage form comprising a sustained-release formulation comprising about 8 mg of naltrexone hydrochloride, and a sustained-release formulation comprising about 90 mg of bupropion hydrochloride, HPC, HPMC, MCC, and lactose monohydrate with an in vitro naltrexone hydrochloride dissolution profile of in a dissolution test of USP Apparatus 2 Paddle Method at 100 rpm in a dissolution medium of water at 37 °C of:
a) between 39% and 70% of naltrexone released in one hour: and
b) between 62% and 90% of naltrexone released in two hours.
Claims 1-8 of U.S. Patent No. 7,375,111 B2 and claim 1 of U.S. Patent No. 8,088,786 B2 recite an oral dosage form comprising a sustained-release formulation of naltrexone and bupropion.
Claims 1-8 of U.S. Patent No. 7,375,111 B2 and claim 1 of U.S. Patent No. 8,088,786 B2 do not specify the release profile of sustained release dosage form.
This deficiency is cured by Shashoua, Kaiko et al., Vergnault et al., and Caruso et al. whose teachings and the rationale are discussed above and applied in the same manner.
Although the patent and instant claims are not identical, they are not patentably distinct from each other because claims in both applications are drawn to the same formulation.
Response to Applicants’ arguments:
Argument regarding the nonstatutory obviousness-type double patenting rejection is basically the same as the above 103 rejection, thus the response discussed above applies here as well and is not persuasive for reason discussed above.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HONG YU whose telephone number is (571)270-1328. The examiner can normally be reached on 9 am - 5:30 pm.
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/HONG YU/
Primary Examiner, Art Unit 1614