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 .1
Status of Claims
Claims 68 and 79 are pending.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 June 272025 has been entered.
Claim Interpretation
Currently Amended claim 68 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) about 300 mg of buprenorphine
free base; and (ii) a first means for achieving sustained release of the
buprenorphine free base to provide μ-opioid receptor occupancy in the human
ranging from about 70% to about 90%; and
(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) about 100 mg of buprenorphine free base; and (ii) a second means
for achieving sustained release of the buprenorphine free base to provide μ-opioid
receptor occupancy in the human ranging from about 70% to about 90%.
Claim 68 is broadly and reasonably interpreted to encompass a broad category of compositions due to the presence of the terms “comprising,” “about” and “to provide.”
The term “about 70 to about 90%” 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 terms “comprising” and “to provide” are broadly and reasonably interpreted as including compositions for both a) and b) where the composition comprises elements beyond the 300 mg buprenorphine free base and sustained-release component currently claimed. The open ended nature of the term comprising allows for other components to achieve the intended use to provide μ-opioid receptor occupancy in the human ranging from about 70% to about 90%,i.e. great than 60%. For example, a hypothetical composition sufficient to achieve the intended use 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 intended use 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.2 Formulation D is defined in the specification as follows:
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Accordingly, prior art teaching a formulation of Formula D, that is established to be the claimed “means for” achieving the intended use “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.
New 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 and 79 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). Norton ‘270 has issued from US Pub 20130203796A1 (Norton US Pub 796), the prior art previously 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,” “to provide,” and “about.” The broad scope in terms of “about,” “to provide,” and “comprising” allow for other μ-opioid type drugs/molecules and excipients as a means for “to provide” the intended use of 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 intended use of μ-opioid receptor occupancy.
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) about 300 mg of buprenorphine
free base; and (ii) a first means for achieving sustained release of the
buprenorphine free base to provide μ-opioid receptor occupancy in the human
ranging from about 70% to about 90%; and
(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) about 100 mg of buprenorphine free base; and (ii) a second means
for achieving sustained release of the buprenorphine free base to provide μ-opioid receptor occupancy in the human ranging from about 70% to about 90%.
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) and (b) 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 that 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 intended use limitation of claim 68, regarding the intended use “to provide μ-opioid receptor occupancy in the human ranging from about 70% to about 90%.”
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, 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 intended 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.
First, 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.
A PHOSITA would routinely optimize formulations of buprenorphine to treat opioid use disorder in patients in need, as the PHOSITA would recognize that the intended 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.
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 intended use of μ-opioid receptor occupancy would be present in the prior art compositions of Norton, whether explicitly taught or not.
The rationale to support a finding of obviousness are the teachings from Norton ‘270 patent with regard to adjustment of months treatment claimed and intended use of 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 an intended use 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.
RESPONSE TO ATTORNEY ARGUMENTS:
The Attorney response states 35 USC 112(f) with regard to claim construction “[a] structure disclosed in the specification qualifies as a 'corresponding structure' if the
specification or the prosecution history 'clearly links or associates that structure to the
function recited in the claim."'3
The Attorney response argues each "means for" in claim 68 is linked to a flowable composition of (ii) 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 (iii) about 50 wt% of N-methyl-2-pyrrolidone.
The Attorney response states this particular “means for” formulation is shown with Formulation D of Example 1, see paragraph 65. 4
The Attorney response states the ‘796 patent is silent with regard to the μ-opioid receptor occupancy, let alone achieving about 70% to about 90% μ-opioid receptor occupancy in a human.
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. Additionally as detailed above, Norton teaches a formulation(s) that encompass Formulation D, which has been established by the specification and the prosecution history to demonstrate the intended use of μ-opioid receptor occupancy as claimed.
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 68 and 79 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 68, 69 and 72 of copending Application No. 19/085,650 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because they are directed to the same subject matter.
Examined claim 68 has been discussed above in the claim interpretation section and its contents are incorporated herein. Claim 79 discloses wherein the first and second means are the same. Reference application claims discloses a non-patentably distinct method as detailed below.
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Reference claims 69 and 72 disclose various ranges of about 250 mg to about 350 mg, specifically about 300 mg buprenorphine.
As noted above, reference claim 68 discloses a method of administering to treat opioid use disorder (as claimed) a formulation that teaches and encompasses an obvious formulation of the present invention’s formulation D, in periods of time as claimed by examined invention’s method. Accordingly, with regard to the intended use of % μ-opioid receptor occupancy, because the reference application encompasses formulation D, the reference application composition would necessarily possess the claimed intended use of % μ-opioid receptor occupancy.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion and Correspondence
No claims are allowed. 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
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623
1 This application is a CON of 17/217,914, filed 03/30/2021, issued as US PAT 11839611. 17/217,914 is a CON of application 15/523,986 filed 05/03/201 issued as US 7 PAT 11000520. 15/523,986 is a 371 of International PCT/IB2015/002269 filed 11/06/2015, which claims earliest priority to USSN 62/076854 filed on Nov 7 2014.
2 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.
3 Ex parte Gleave, Appeal No. 2012-004973, page 7 (PTAB, Jan. 22, 2014), citing B. Braun Med., Inc. v. Abbott Labs., 124 F.3d 1419, 1424 (Fed. Cir. 1997). Therefore, "'the PTO may not disregard the structure disclosed in the specification corresponding to such language when rendering a patentability determination."' Id., p. 5,
citing M.P.E.P. § 2181.
4 achieves sustained release for at least 28 days of the buprenorphine in the
form of the free base, wherein the sustained release provides a μ-opioid receptor
occupancy (as measured by a maximum effect model of Equation 1) of 70-90% in a human
(see ,r [0065]).