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 .
Status of Claims
Claims 68, 79 and 88-101 are pending.
Terminal Disclaimer
The terminal disclaimer filed on May 18 2025 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of 19/085,650 has been reviewed and is accepted. The terminal disclaimer has been recorded.
Claim Interpretation
Claim 68 is broadly and reasonably interpreted to encompass a broad category of compositions due to the presence of the terms “comprising,” and “about.’
The term “about 70 to about 90%” of μ-opioid receptor occupancy is not specifically recited in the specification. But based on the specification, where various examples of ranges such as about 65% to about 85%, etc., a broad and reasonable interpretation of the claimed range is a μ-opioid receptor occupancy in the human greater than 60%.See paragraph 34
The term “comprising” is broadly and reasonably interpreted as including compositions for both a) and b) where the composition comprises elements beyond the (i) 300 or 100 mg buprenorphine free base and (ii) sustained-release component currently claimed. The open-ended nature of the term comprising allows for other components to achieve the μ-opioid receptor occupancy in the human ranging from about 70% to about 90% , i.e. greater than 60%, within the claimed time frames of the two ending wherein clauses (within two months and where such opioid occupancy is maintained for 28 days follow each subcutaneous injection).
For example, a hypothetical composition sufficient to achieve the goal to provide the μ-opioid receptor occupancy claimed could conceivably comprise 300 mg of buprenorphine free base in a de minimis amount of sustained release component, while further comprising any amount of a buprenorphine metabolite, salt and/or prodrug available so to achieve the goal of μ-opioid receptor occupancy claimed. Support for the amendment can be found in the specification at paragraph 34, pages 10-11, noting μ-opioid receptor occupancy of greater than 60% to about 90% and/or about 65% to about 85%, along with other examples of receptor occupancy ranges. The means for achieving this opioid receptor occupancy is noted with a particular formulation of the specification, Formulation D.1 Formulation D is defined in the specification as follows:
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Accordingly, prior art teaching a formulation of Formula D, that comprises the recited amounts of buprenorphine, that is established to be the claimed “means for” achieving the “μ-opioid receptor occupancy” claimed, such as achieving an occupancy greater than 60%, will necessarily possess this property of “μ-opioid receptor occupancy” as claimed.
Note, while the claims have been amended to recite “consisting” in an effort to limit the claims of the (i) component, the claimed composition nonetheless recites the open-ended term “comprises” which allows for the broader definition recognized by the Examiner as detailed above.
Furthermore, with regard to the “wherein” clauses at the end of claim 68 where the opioid occupancy claimed is “within two months after the first injection of the first composition, and” and opioid occupancy is “is maintained for 28 days following each subcutaneous injection thereafter,” such properties are expected to be present in Formulation D and also prior disclosing Formulation D (see Norton ‘270 patent claims 1-10 and claims 11-15) in the interpretation of the broad scope as detailed above.
At the May 26, 2026 Interview and per the May 18, 2026 Attorney response, Applicant states the claims are means plus function claims as per 35 USC 112(f). Specifically, the particular limitations (a)(i) and (b)(i) are argued to be given interpretation under 35 USC 112(f) as means plus function limitations to be limited to the embodiment of paragraph 27 detailed above, rather than the broader interpretation noted by the Examiner above. In determining whether claim 68 is a means plus function claim, a three-prong analysis of claim 68, as per MPEP 2181 is required to determine if 35 USC 112(f) is properly invoked.
The first prong is whether the term “means” is employed and this is satisfied for claim 68, per the statue and MPEP 2181(I.), bullet point (a). See also Greenberg v. Ethicon Endo-Surgery, Inc. 91 F.3d 1580 (Fed. Cir. 1996).
The second prong is whether the “means” term is modified by functional language, i.e. “for” and this is satisfied for claim 68, per the statue and MPEP 2181(I.), bullet point (b).
The third prong is whether the “means” is NOT modified by sufficient structure, material, or acts for performing the claimed function, per the statue and MPEP 2181(I.).
The third prong is not satisfied as it both (a)(i) and (b)(i) are modified by structure, material and acts to perform the claimed function of sustained release where the “first means for achieving sustained release” is achieved by the act of administering to the human, a subcutaneous injection (act and/or structure of sustained release via subcutaneous injection) comprising an opioid receptor agonist consisting of buprenorphine in amount equivalent to about 300 mg or 100 mg of buprenorphine free base (material capable of sustained release cited by the prior art).
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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 68, 79 and 88-101 are rejected under 35 U.S.C. 103 as being unpatentable over US Patent 8,975,270 B2 (Norton ‘270 Patent), cited by Applicant on IDS filed Nov 11 2022 (Ref No. 42). The Norton ‘270 patent has issued from US Pub 20130203796A1 (Norton US Pub 796), which has been cited by the Examiner in previous office actions.
As discussed above, claim 68 is broadly and reasonably interpreted with regard to the limitations of “comprising,” and “about.” The broad scope in terms of “about” and “comprising” allow for other μ-opioid type drugs/molecules and excipients as a means for to achieve the occupancy of the receptors as claimed. Also as detailed above, Formulation D of the specification is said to provide the claimed μ-opioid receptor occupancy, accordingly a teaching of Formulation D in the art will teach the μ-opioid receptor occupancy.
Regardless of whether means plus function precludes a finding of a broad interpretation of the claims rejected below, the claims fail the requirement of 35 USC 112(f) under the third prong of the bullet point (c) of MPEP 2181 (I.) requiring a lack of modifier of structure, materials or acts for performing the claimed function, which claim 69 does not as detailed in the claim interpretation section above.
Alternatively, even if the claims fall under the provisions of 35 USC 112(d), Formulation D, an embodiment of the clamed method and the means plus function embodiment of the claims argued by Applicant, is taught by Norton ‘270 patent, and therefore its claimed properties of μ-opioid receptor occupancy claimed, along with the time periods of the “wherein” clauses are present in the art, whether expressly taught or not. See obviousness below.
Claim 68 (amendments in bold) is directed to a method of treating opioid use disorder in a human in need thereof, the method comprising:
(a) administering to the human, by subcutaneous injection once per month for
two months, a first composition comprising: (i) an opioid receptor agonist consisting of buprenorphine in an amount equivalent to about 300 mg of buprenorphine free base; and (ii) a first means for achieving sustained release of the opioid receptor agonist
(b) administering to the human, by subcutaneous injection once per month beginning with a third month and for at least four months, a second composition comprising: (i) an opioid receptor agonist consisting of buprenorphine in an amount equivalent to about 100 mg of buprenorphine free base; and (ii) a second means for achieving sustained release of the opioid receptor agonist,
wherein the human's μ-opioid receptor occupancy by the opioid receptor
agonist ranges from greater than or equal to 70% up to about 90% within two
months after the first injection of the first composition, and
wherein said μ-opioid receptor occupancy ranging from greater than or
equal to 70% up to about 90% is maintained for 28 days following each
subcutaneous injection thereafter.
Regarding claim 68’s preamble of treating opioid use in a human in need, Norton ‘270 patent teaches that buprenorphine is most often used to treat symptoms arising from opioid addiction and the long-term relief of pain. See column 1, lines 48-49.
Regarding limitations (a)(i) and (b)(i) of compositions for sustained release of buprenorphine free base by both a first means and second means, Norton ‘270 patent discloses its formulation (i.e. a means) is related to a buprenorphine sustained release delivery system for treatment of conditions ameliorated by buprenorphine compound, a metabolite, or a prodrug thereof. See column 1, lines 15-25.
As required by the subcutaneous limitation, Norton ‘270 patent discloses subcutaneous injectable formulations of its buprenorphine formulations at Figure 1 and see BRIEF DESCRIPTION OF THE DRAWINGS, noting where FIG. 1 illustrates 49 day release of buprenorphine from selected ATRIGEL formulations of buprenorphine subcutaneously injected. See column 8, lines 50-55. See also multiple references to subcutaneous injection throughout Norton ‘270 patent.
Regarding the limitations of claim 68 and dosages of (a) 300 mg buprenorphine and (b) 100 mg buprenorphine, Norton ‘270 patent teaches a typical flowable composition effective for such sustained delivery over a 1 month period should contain from about 3 to about 300 mg of buprenorphine (see column 26, line 1; and claim 8), dosages that encompass the claimed 300 mg and 100mg doses. Norton ‘270 patent teaches a buprenorphine sustained release delivery system capable of delivering buprenorphine, a metabolite, or a prodrug thereof for a duration of about 14 days to about 3 months. See abstract and column 2,lines 13-17. The buprenorphine sustained release delivery system provides in situ 1-month and 3-month release profiles characterized by an exceptionally high bioavailability and minimal risk of permanent tissue damage and typically no risk of muscle necrosis. See column 2, lines 21-25.
While Norton ‘270 patent teaches all the limitations of claim 68 in terms of treating opioid use disorder (i.e., addiction) with first and/or second compositions of claimed buprenorphine compositions, and it does teach once a month administration, as well as duration lengths of about 14 days to about 3 months, Norton does not explicitly recite once a month injection for two months and once a month injection for the third month and for at least four months. Also noted is that Norton ‘270 patent does not explicitly recite the limitation of claim 68, regarding the use “to provide μ-opioid receptor occupancy in the human ranging from about 70% to about 90%” within the claimed time frames of the wherein clauses “two months after the first injection” and “maintained for 28 days following . . . .”
First, in response to lack of teaching of treating opioid addiction over several months, a person having ordinary of skill in the art (PHOSITA) would have a reasonable expectation of success practice this limitation as it would been prima facie obvious to treat opioid addiction over several months, where doses of the buprenorphine treatment would be lowered after an initial higher loading dose followed by subsequent lower maintenance doses over time. Norton discloses its formulations have delivery durations of about 14 days to about 3 months, and which when taken in the context of opioid addiction as a long term debilitating condition, would lead to a PHOSITA to dose a patient for the periods claimed, inclusive of a third and fourth month. See also MPEP 2144.05(I).
Norton ‘270 patent teaches its composition effective for a sustained delivery over a 1 month period should contain from about 3 to about 300 mg of buprenorphine, as well as the 14 days to 3 months duration, which is a teaching buprenorphine dosing is routinely optimizable with a reasonable expectation of success. The amounts of active agents to be used, the pharmaceutical forms, e.g., tablets, etc.; mode of administration, flavors, surfactant are all deemed obvious since they are all within the knowledge of the skilled pharmacologist and represent conventional formulations and modes of administration. Furthermore, it is obvious to vary and/or optimize the amount of buprenorphine provided in the composition, according to the guidance provided by Norton, to provide a composition having the desired properties such as the desired (ratios, concentrations, percentages, etc.). It is noted that "[W]here 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, 456, 105 USPQ 233, 235 (CCPA 1955).
Second, in response to the lack of explicit recitation of the use limitation of μ-opioid receptor occupancy as claimed, a person having ordinary of skill in the art (PHOSITA) would have a reasonable expectation of success in achieving this µ-opioid receptor occupancy as claimed based off two teachings from Norton ‘270 patent.
As discussed above, the broad scope of claim 68 in terms of the composition “comprising” Norton ‘270 patent teaches a flowable composition comprising
at least one biodegradable thermoplastic polymer
at least one biodegradable thermoplastic polymer
1 wt.% to 10 wt. % of buprenorphine, a metabolite, or a prodrug thereof. See column 2, lines 37-51.
Note, while the claims have been amended to recite “consisting” in an effort to limit the claims of the (i) component, the claimed composition nonetheless recites the open ended term “comprises” which allows for the broader definition recognized by the Examiner as detailed above.
A PHOSITA would routinely optimize formulations of buprenorphine to treat opioid use disorder in patients in need, as the PHOSITA would recognize that the use limitation of μ-opioid receptor occupancy in the human ranging from about 70% to about 90%, i.e., greater than 60% occupancy is known goal to achieve. As detailed above, a PHOSITA would recognize that by Norton ‘270 patent teaches compositions of up 1 to 10 wt. % buprenorphine, metabolite or a prodrug, which can be routinely optimized in amounts to adjust such buprenorphine, metabolite or prodrugs to achieve a μ-opioid receptor occupancy as claimed.
The open ended nature of the term comprising allows for other components to achieve the μ-opioid receptor occupancy in the human ranging from about 70% to about 90% , i.e. greater than 60%, within the claimed time frames of the two ending wherein clauses (within two months and where such opioid occupancy is maintained for 28 days follow each subcutaneous injection).
For example, a composition sufficient to achieve the goal to provide the μ-opioid receptor occupancy claimed could conceivably comprise 300 mg of buprenorphine free base in a de minimis amount of sustained release component, while further comprising any amount of a buprenorphine metabolite, salt and/or prodrug available so to achieve the goal of μ-opioid receptor occupancy claimed. Support for the amendment can be found in the specification at paragraph 34, pages 10-11, noting μ-opioid receptor occupancy of greater than 60% to about 90% and/or about 65% to about 85%, along with other examples of receptor occupancy ranges.
Alternatively, as established by the record and the specification, an embodiment of claim 68, where Formulation D has been established as the means for achieving the claimed μ-opioid receptor occupancy.
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As detailed below, prior art formulations encompassing Formulation D is/are taught by Norton ‘270 patent as follows. See claims 1-10 and claims 11-15 directed to methods of treating a patient having an opioid dependency. Note the reproduction of claims from Norton below.
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Formulation D was known in the prior art (See claims above). Therefore, the use limitation of μ-opioid receptor occupancy, within the time frame limitations of the two wherein clauses, would be present in the prior art compositions of Norton, whether explicitly taught or not. Note per MPEP 2112.01 (If the composition is physically the same, it must have the same properties). As detailed above, even if Applicant was correct in their interpretation that the claims are eligible as means plus function claims per 35 USC 112(f), Formulation D, an embodiment of the clamed method and embodiment under 112(f) argued by Applicant is taught by the prior art and therefore its claimed properties of μ-opioid receptor occupancy are present.
Note that Norton ‘270 patent explicitly teaches its buprenorphine sustained release delivery system is capable of delivery buprenorphine, metabolite or a prodrug for a duration of 14 days to about 3 months. See abstract and Column 1, Summary of the Invention. Norton ‘270 patent explicitly teaches its buprenorphine sustained release delivery system provides in situ 1-month and 3-month release profiles characterized by an exceptionally high bioavailability and minimal risk of permanent tissue damage and typically no risk of muscle necrosis. See abstract and Column 1, Summary of the Invention. As noted above, because Norton ‘270 patent teaches a formulation that reads upon the claimed formulation, where such μ-opioid receptor occupancy as claimed is necessarily present, and it notes overlapping time frames of buprenorphine delivery with those time frames of occupancy claimed by the wherein clauses of claim 68. See MPEP 2144.05 (Obviousness of Similar and Overlapping ranges establishing a prima facie case of obviousness).
The rationale to support a finding of obviousness are the teachings from Norton ‘270 patent with regard to adjustment of months treatment claimed and μ-opioid receptor occupancy these limitations routinely optimized to achieve by the PHOSITA, or where Norton teaches a formulation that encompasses Formulation D of the invention, established to possess such a use of μ-opioid receptor occupancy, in overlapping time frames of duration of delivery to the claimed time periods of μ-opioid receptor occupancy.
Regarding claim 79 where the first and second means are the same, by Norton ‘270 patent discloses subcutaneous injectable formulations of its buprenorphine formulations at Figure 1 and see BRIEF DESCRIPTION OF THE DRAWINGS, noting where FIG. 1 illustrates 49 day release of buprenorphine from selected ATRIGEL formulations of buprenorphine subcutaneously injected. See column 8, lines 50-55. See also multiple references to subcutaneous injection throughout Norton.
It would have been prima facie obvious to use the same means/formulation over extended periods of time as per claim 79, as Norton ‘270 patent discloses after an initial dose, follow up doses occur at regular intervals of time of up to 30 days, see paragraph 4. Norton discloses its formulation has a duration of about 14 days to about 3 months. See abstract and paragraph 7. Due to the extended nature of treating a long term disease/condition such as opioid addiction and the fact that Norton’s buprenorphine formulation has such taught dose scheduling and dose durations, one of ordinary skill in the art would repeat the dosing/means with the same buprenorphine formulation as suggested by what is known in the art and the teachings of Norton.
Regarding claims 88, 90, 93 and 95 (wherein the (a)(i) opioid receptor agonist consists of 300 mg buprenorphine free base) and claims 89, 91, 94 and 96 (wherein the (b)(i) opioid receptor agonist consists of 100 mg buprenorphine free base), Norton ‘270 patent teaches a typical flowable composition effective for such sustained delivery over a 1 month period should contain from about 3 to about 300 mg of buprenorphine (see column 26, line 1; and claim 8), amounts that encompass the claimed 300 mg dose. See MPEP 2144.05 (Obviousness of Similar and Overlapping ranges).
Regarding claims 92 and 97 wherein (a)(i) consists of 300 mg buprenorphine free base and (b)(i) consists of 100 mg buprenorphine free base, Norton ‘270 patent teaches a typical flowable composition effective for such sustained delivery over a 1 month period should contain from about 3 to about 300 mg of buprenorphine (see column 26, line 1; and claim 8), dosages that encompass the claimed 300 mg dose. See MPEP 2144.05 (Obviousness of Similar and Overlapping ranges).
Regarding claim 98 -101 claiming buprenorphine pharmaceutically acceptable salts or free base of (a)(i) and/or (b)(i), Norton ‘270 patent teaches both buprenorphine salts and free base form in multiple instances. See for example claim 1.
RESPONSE TO ATTORNEY ARGUMENTS:
As was discussed at the Attorney initiated interview on May 26, 2026 summarizing the Attorney response dated May 18, 2026, Table A of the response showing support for amendment claim 68 (re: “consisting” and “wherein” clauses) was discussed. Further, Table B of the response supporting new claims 88-101 was mentioned.
The Attorney response states (at page 12 of the response)
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The Attorney response states a proper interpretation of amended claim 68 is per
35 USC 112(f) and MPEP 2181 citing to In re Donaldson. The Attorney response states the broadest reasonable interpretation may give means plus function language is per paragraph 6, i.e. “components (a)(ii) and (b)(ii) have been linked to a flowable composition of about 32 wt% of a 50:50 poly(DL-lactide-co-glycolide) copolymer
having a carboxy terminal group and having an average molecular weight of about 9,000 Daltons to about 19,000 Daltons, and about 50 wt% of N-methyl-2-pyrrolidone.” See pages 11-13 of Applicant’s response.
The Attorney response states regardless of the open nature of the claim language, the Office is required to interpret (a)(i) and (b)(i) as argued above, and because of this interpretation, the Prima Facie case of Obviousness has NOT been established. See page 13 to 16 of Applicant’s response. The Attorney response states the previous obviousness rejection was improper over the ‘796 patent due to its lack of teaching of claim elements/limitations, citing what a PHOSITA could have done with providing motivation evidence (citing to MPEP 2143.01 (IV); KSR and In re Kotzab (citations omitted). See page 13 bridging to page 14.2
In response, for the reasons stated previously in the prosecution, despite the invocation of the “means” language in the claims to limit to Applicant’s embodiment of paragraph 6, the claims are not necessarily limited to the paragraph 27 embodiments.
As detailed above, regardless of whether means plus function precludes a finding of a broad interpretation of the claims rejected below, the claims fail the requirement of 35 USC 112(f) under the third prong of the bullet point (c) of MPEP 2181 (I.) requiring a lack of modifier of structure, materials or acts for performing the claimed function, which claim 68 does not as detailed in the claim interpretation section above.
a three part analysis of the applicability of the 35 USC 112(f).
The Attorney response states that the Examiner fails provide evidence that the ‘796 Norton formulation has the same function as claimed with regard to μ-opioid receptor occupancy.
In response, as detailed above in the obviousness rejection, the broad scope of claim 68 and teachings from the Norton ‘270 patent allow for adjustment an inclusion of other forms of buprenorphine to routinely optimize μ-opioid receptor occupancy to treat opioid use disorders in a human subject in need, in overlapping ranges of time frames as recited in the wherein clauses of claim 68. Additionally, as detailed above, Norton teaches a formulation(s) that encompass Formulation D (See claims 1-10 and claims 11-15), which has been established by the specification and the prosecution history to demonstrate the use of μ-opioid receptor occupancy as claimed.
The limitation of μ-opioid receptor occupancy, within the time frame limitations of the two wherein clauses, would be present in the prior art compositions of Norton, whether explicitly taught or not.. Note per MPEP 2112.01 (If the composition is physically the same, it must have the same properties). As detailed above, even if Applicant was correct in their interpretation that the claims are eligible as means plus function claims per 35 USC 112(f), Formulation D, an embodiment of the clamed method and embodiment even under 112(f) argued by Applicant is taught by the prior art and therefore its claimed properties of μ-opioid receptor occupancy are present.
Conclusion and Correspondence
No claims are allowed. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to WILLIAM LEE whose telephone number is (571)270-3876. The examiner can normally be reached M-F.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam C. Milligan can be reached at (571) 270-7674. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/WILLIAM Y LEE/Examiner, Art Unit 1623
/GEORGE W KOSTURKO/Primary Examiner, Art Unit 1621
1 As discussed in the previous Final Office Action, the means for limitation, “A first means for achieving sustained release of the buprenorphine free base,” is supported in the specification at Example 1 [[0044]]; [[0027]] and [[0028]] as per Formulation D. Specification support for the claim limitation, “A second means for achieving sustained release of the buprenorphine free base,” is said to be the same, Example 1 and [0027]; [0028] and [0044], as per Formulation D.
2 With regard to the suitability of an obviousness rejection, putting aside the propriety of the applicability of means plus function, Attorney response argues the obviousness analysis is not simply whether a “once a month injection [of buprenorphine] for two months and once a month injection [of buprenorphine] for the third month and for at least four months” at a lower dose would have been obvious but rather, whether it would have been obvious to achieve and maintain the claimed μ-opioid receptor occupancy with the claimed dosing regimen, i.e., by using the route and timing of administration as well as the formulations recited. See e.g., Teva, citations omitted.
Prosecution Insights